https://wiki.app.uib.no/mriwiki/api.php?action=feedcontributions&user=St03724&feedformat=atommriwiki - User contributions [en]2024-03-29T14:15:58ZUser contributionsMediaWiki 1.35.6https://wiki.app.uib.no/mriwiki/index.php?title=Frits_Thorsen%C2%B4s_group&diff=320Frits Thorsen´s group2011-08-30T10:52:35Z<p>St03724: </p>
<hr />
<div>== '''A novel animal model for characterization and treatment of melanoma metastasis''' ==<br />
<br />
=== '''Background''' ===<br />
Brain metastasis is a complication occurring in one third of all cancer patients. The annual incidence in the US is 170 000. Brain metastases is the commonest intracranial cancer, appearing 10 times more often than primary brain tumors (1). The most common sources of metastatic brain lesions involve the lung (50-60%), breast (15-20%), skin (5-10%) and gastrointestinal tract (4-6%). <br />
<br />
Patients with melanoma metastatic spread to the central nervous system (CNS) have poor prognosis (2, 3). Treatment strategies available today are ineffective, with low response rates, as current chemotherapeutic agents are ineffective. Clearly there is a need for suitable animal models in which spontaneous CNS metastases develop when cancer cells metastasize from the primary lesion in a manner that reflects the patient setting. We have currently developed such models, which will enable us to study the biology and the treatment of melanoma brain metastases.<br />
<br />
=== '''Development of new metastatic animal models''' ===<br />
We have recently developed a novel model system where tumor cells from human melanoma brain metastases are injected systemically in immunodeficient mice and metastasize to the mouse brain (4). This animal model recapitulates most steps of the metastatic cascade, and a better understanding of the molecular mechanisms behind tumor metastasis may thus be obtained.<br />
<br />
[[File:Frits_Figure1.jpg|frame|left||'''Figure 1. Development of a highly tumorigenic melanoma tumor cell line from a patient brain metastasis'''. A) The H1 melanoma cell line in cell culture. B) MR picture (T2 weighted) of tumor development 4 weeks after injection.]]<br />
<br />
[[File:Frits_Figure3.jpg|frame|right||'''Figure 3. Systemic tumor metastases after intracardial injections of H1_GFP_Luc cell line'''. A) 3-8 weeks after injections, tumor colonization and growth in several organs was seen by bioluminescence imaging. B) Multiple metastases in the cerebrum could be seen using T1 weighted MR imaging after contrast injection. C) Multiple brain metastases in the cerebrum were confirmed by histology. D) Several brain metastases were found in the brainstem. E) The melanocytic properties of the animal brain metastases were confirmed by immunhistochemistry (HMB-45, Melan-A, Tyrosinase).]]<br />
<br />
[[File:Frits_Figure2.jpg|frame|left||'''Figure 2. Tumorigenicity of the H1_dsRed cell line'''. A) 3 weeks after injection of the H1_dsRed cell line subcutaneously in matrigel, large tumors were observed. B) By fluorescence microscopy, the tumor cells (red) could be distinguished from the host cells (green), using an eGFP nod/SCID mouse strain. C) A larger magnification of the tumor area showed that dsRed negative blood vessels from the host extended into the tumor tissue (arrow). D) The eGFP mouse strain developed by Prof. Rolf Bjerkvig.]]<br />
<br />
[[File:Frits_Figure4.jpg|frame|left||'''Figure 4. Establishing new cell lines from melanoma metastases in various mouse organs'''. The cells were 100% positive for GFP (green), demonstrating their origin from the H1_GFP_Luc injected tumor cells. The GFP+ tumors developed and were excised from GFP- NOD/SCID mice. A) Tumor cell line established from a lung tumor. B) Tumor cell line established from an ovary tumor.]]<br />
<br />
* '''Development of metastatic cell lines from a melanoma brain metastasis'''<br />
An important question is whether melanoma cells excised from brain metastases in patients would metastasize selectively to the brain in a mouse model system, if the tumor cells are injected into the bloodstream.<br />
<br />
In order to study this we developed several tumor cell lines from a brain metastases harvested from a patient with malignant melanoma (Figure 1A). To verify the tumorigenicity of the cell line, melanoma cells were injected directly into the brains of immunodeficient nod/SCID mice. During a time period of 3-4 weeks, large lesions developed (Figure 1B). <br />
<br />
* '''Insertion of reporter genes to study tumor cell colonization and growth in vivo.'''<br />
We then generated new cell lines, by labeling the tumor cells with suitable reporter genes. First, we inserted the DsRed reporter gene into the H1 cell line, using a lentiviral vector, resulting in the H1_dsRed cell line. This cell line was embedded in matrigel, and injected subcutaneously into eGFP nod/SCID mice (5). After around 4 weeks, large tumors developed subcutaneously (Figure 2).<br />
<br />
Systemic in vivo tumor development can also be detected by bioluminescence imaging of the animals. Thus we used a retroviral GFP/Luciferase construct, and obtained a 100% GFP/Luciferase positive cell line after FACS sorting. These cells were injected into the left ventricle of the heart in nod/SCID mice, and tumor development was studied by bioluminescence imaging. After 3-8 weeks, the animals developed new tumors in most organs of the mouse body (Figure 3A). T1w/T2w MRI showed multiple metastases within the CNS (Figure 3B). Around 30 micrometastases (sizes 0.1-0.8mm) were detected in the animal brain by histology (Figure 3C, 3D). The melanocytic properties of the tumors were confirmed by immunohistochemistry (Figure 3E).<br />
<br />
=== '''Ongoing research activities''' ===<br />
We have already injected the H1_GFP_Luc metastatic melanoma cell line into several mice, and collected tumors from lung, bone, CNS and ovary. These tumors have been plated, and new cell lines have been established (Figure 4). We are currently reinjecting these new cell lines into mice, to see if the tumor cells home specifically to the organ they were established from.<br />
<br />
The H1_GFP_Luc tumor cells are also being injected into the blood stream of immunodeficient mice, and the colonization and growth of new tumors are being detected using advanced preclinical MR imaging. It has previously been shown that breast cancer cells prelabelled with micron-sized iron oxide particles (MPIOs) and therafter injected intra-cardially into mice, can be tracked by MRI as single cells in the mouse brain (6). In a similar manner, we are labeling the H1_GFP_Luc melanoma cell line with Fedex (7), and performing T2 and T2* weighted MR imaging.<br />
<br />
Brain metastases are very often highly vascularized, a process driven primarily by VEGF. In this part of the project, we are specifically targeting the neovascularization process using bevacizumab treatment. Bevacizumab, which is a VEGF antibody, has previously been used in advanced, primary cancers (8-10). Just recently, the antibody has also been FDA approved for use on patients with brain metastasis. However, there is limited knowledge on treatment effects and biological responses after bevacizumab treatment on metastatic brain tumors. Our metastatic brain tumor modell develops highly angiogenic tumors, and thus mimic the vascular, metastatic brain tumors seen in patients. After injecting the H1_GFP_Luc cell line in the left ventricle of the mice, we are treating the animals with clinically relevant bevacizumab doses, injected intraperitoneally once a week for 3 weeks. The animals are then be studied with MR imaging.<br />
<br />
See also Terje Sundstrøm PhD outline at https://wikihost.uib.no/mriwiki/index.php/Terje_Sundstrøm_PhD_project<br />
<br />
=== '''References''' ===<br />
#Santarelli JG, Sarkissian V, Hou LC, Veeravagu A, Tse V. Molecular events of brain metastases. Neurosurg Focus 22(3):E1, 2007.<br />
#Tarhini AA, Agarwala SS. Management of brain metastasis in patients with melanoma. Curr Opin Oncol 16:161-166, 2004). <br />
#JuanYin J, Tracy K, Zhang L, Munasinghe J, Shapiro E, Koretsky A, Kelly K. Noninvasive imaging of the functional effects of anti-VEGF therapy on tumor cell extravasation and regional blood volume in an experimental brain metastasis model. Clin Exp Metastasis 26:403-414, 2008.<br />
#Wang J, Daphu I, Pedersen PH, Miletic H, Hovland R, Mørk S, Bjerkvig R, Tiron C, McCormack E, Micklem D, Lorens JB, Immervoll H, Thorsen F. A novel brain metastases model developed in immunodeficient rats closely mimics the growth of metastatic brain tumours in patients. Neuropathol Appl Neurobiol 2010 (Resubmitted).<br />
#Niclou S, Danzeisen C, Eikesdal HP, Wiig H, Brons NH, Poli AM, Svendsen A, Torsvik A, Enger PØ, Terzis AJ, Bjerkvig R. A novel EGFP-expressing immunodeficient mouse model to study tumor-host interactions. FASEB J 22:3120-3128, 2008.<br />
#Heyn C, Ronald JA, Ramadan SS, Snir JA, Barry AM, MacKenzie LT, Mikulis DJ, Palmieri D, Bronder JL, Steeg PS, Yoneda DJ, MacDonald IC, Chambers AF, Rutt BK, Foster PJ. In vivo MRI of cancer cell fate at the single-cell level in a mouse model of breast cancer metastasis to the brain. Magn Res Med 56:1001-1010, 2006.<br />
#Babic M, Horak D, Trchova M, Jendelova P, Glogarova K, Lesny P, Herenyk V, Hajek M, Sykova E. Poly(L-lysine)-modified iron oxide particles for stem cell labelling. Bioconjugate Chem 19:740-750, 2008.<br />
#Perez DG, Suman VJ, Fitch TR, Amatruda T 3rd, Morton RF, Jilani SZ, Constantinou CL, Markovic SN. Phase 2 trial of carboplatin, weekly paclitaxel, and biweekly bevacizumab in patients with unresectable stage IV melanoma: a North Central Cancer Treatment Group study, N047A. Cancer 115:119-127, 2009.<br />
#Gonzalez-Cao M, Viteri S, Diaz-Lagares A, Gonzaléz A, Redondo P, Nieto Y, Espinos J, Chopitea A, Ponz M, Martín-Algerra S. Preliminary results of the combination of bevacizumab and weekly Paclitaxel in advanced melanoma. Oncology 74:12-16, 2008.<br />
#Scicher N, Paulitschke V, Swoboda A, Kunstfeld R, Loewe R, Pilarski P, Pehamberger H, Hoeller C. Erlotinib and bevacizumab have synergistic activity against melanoma. Clin Cancer Res 15:3495-3502, 2009.</div>St03724https://wiki.app.uib.no/mriwiki/index.php?title=Terje_Sundstr%C3%B8ms_PhD_project&diff=319Terje Sundstrøms PhD project2011-08-28T20:51:43Z<p>St03724: moved Terje Sundstrøms PhD project to Terje Sundstrøm PhD project</p>
<hr />
<div>#REDIRECT [[Terje Sundstrøm PhD project]]</div>St03724https://wiki.app.uib.no/mriwiki/index.php?title=Terje_Sundstr%C3%B8m_PhD_project&diff=318Terje Sundstrøm PhD project2011-08-28T20:51:43Z<p>St03724: moved Terje Sundstrøms PhD project to Terje Sundstrøm PhD project</p>
<hr />
<div>== '''Molecular biology of melanoma brain metastasis: Potential new therapeutic targets''' ==<br />
<br />
== Terje Sundstrøm ==<br />
<br />
Terje Sundstrøm is a MD from the University of Bergen in 2005, and a resident in neurosurgery at Haukeland University Hospital from 2007. As a medical student he started clinical research in neurosurgery under the supervision of Professor Knut Wester. He has published 8 articles on different neurosurgical topics (http://www.uib.no/persons/Terje.Sundstrom and http://www.neurotrauma.nu). Sundstrøm has during neurosurgical training been recruited to neuro-oncology and translational cancer research. He started his PhD project in January 2011 after being awarded a 3-year scholarship from the Western Norway Regional Health Authority (Helse Vest). His project on melanoma brain metastasis is a part of the Melanoma Metastasis Project headed by Professor Frits Thorsen, Translational Cancer Research Group, Department of Biomedicine, University of Bergen (http://www.uib.no/persons/Frits.Thorsen and https://wikihost.uib.no/mriwiki/index.php/Frits_Thorsen´s_group).<br />
<br />
== Project background ==<br />
<br />
Metastases are responsible for the vast majority of cancer mortality, and brain metastases occur in 1/3 of adults suffering from cancer. Metastases to the brain are 10 times more frequent than primary brain tumors. The number of patients with brain metastases is increasing because treatments for primary cancers are continually improving, and patients are surviving with these diseases longer. The treatment of brain metastases is troublesome and inadequate due to limited effects of cytostatic medications and difficult compromises with respect to consequences of radiation and surgery on surrounding brain structures.<br />
<br />
Melanoma has the highest propensity to metastasize to the brain of all cancers. The median survival time with brain metastases is 6 months. The incidence of melanoma has increased over the last 3 decades, and the death rate continues to rise faster than the rate with most cancers. Recent results have shown that it is possible to develop genetically tailored therapy to various sub-populations of patients with metastatic melanoma ('''1-4''').<br />
<br />
Unfortunately, the mechanisms for metastatic spread of melanoma to the brain are largely unknown. This is due to the lack of relevant in vivo model systems. Patients with brain metastases are often excluded from larger clinical trials, leaving us uncertain about the effect of new therapeutic modalities. New research approaches and treatment strategies are clearly needed to improve the outcome for these patients.<br />
<br />
== Project overview ==<br />
<br />
We have developed competitive animal models to study cancer metastasis and especially to the brain. This project includes extensive use of advanced imaging technology (e.g. 7 Tesla MRI, PET and bioluminescence imaging), as well as state of the art genetic and proteomic analyses through close collaboration with national and international core facilities. Our model system has unique translational possibilities in characterizing cancer metastasis and developing new target specific treatment. Biological and therapeutical considerations have motivated us to study melanoma, but any cancer can in principle be studied.<br />
<br />
In our experimental model, cell lines from human melanoma brain metastases and cell lines from primary, cutaneous melanomas are injected into the left cardiac ventricle of immunodeficient mice. In our spontaneous model, the same cell lines are injected into the skin. We have been able to show that these cells form tumors in the mice, and that the metastatic cell populations more aggressively target the brain. Some of this work has already been published ('''5'''). Preliminary results were recently presented at the AACR in the USA, and as a consequence of this, we are now in the process of establishing a cooperation with the manufacturer of one of the most promising new drugs for metastatic melanoma (Vemurafenib/PLX4032; http://www.plexxikon.com) ('''3''').<br />
<br />
It has previously been shown that breast cancer cells prelabelled with micron-sized iron oxide particles (MPIOs) and thereafter injected intracardially into mice, can be tracked by MRI as single cells in the mouse brain ('''6'''). We are currently doing comprehensive MRI studies to elucidate the metastatic patterns and growth potentials of our cell lines by using a similar particle, called Fedex ('''7'''). This work is done in collaboration with Professor Arvid Lundervold at our department. We are able to visualize single cells labelled with Fedex in the animal brains, and through mathematical modelling we can quantify the brain cell load and follow the development of brain metastases, as well as the interesting aspects of tumor dormancy in the brain. This model system gives us a reliable tool, both quantitatively and qualitatively, to study the efficacy of new treatments.<br />
<br />
We are now working to characterize functional and structural differences in the metastatic patterns of cell lines derived from primary tumors and metastases (e.g. by 7 Tesla MRI, PET and bioluminescence imaging). This work will provides us with a groundwork for a more target specific identification and validation of genetic and epigenetic alterations responsible for melanoma disbursement and growth in the brain. Through functional assessments of candidate genes by overexpression and knockout studies, we hope to contribute to the development of more target specific and effective anti-tumor therapy. We are also in the process of investigating the significance of miRNAs in the metastatic process, by selective insertion of candidate miRNAs into the tumor cells.<br />
<br />
== Figure ==<br />
<br />
[[File:Figure_1.jpg|200px|thumb|left| ]]<br />
'''Modeling melanoma brain metastasis in the mouse'''<br />
A. MRI T1 with contrast 6 weeks after intracardial injection showing a contrast-enhancing tumor in the right hemisphere.<br />
B. 3D brain model of the same animal as in A illustrating multiple metastases.<br />
C. Optical imaging 3 weeks after intracardial injection demonstrating both abdominal and brain tumors.<br />
D. Mathematical modeling with automatic quantification of single Fedex labeled cells in the brain based on MRI T2*/MGE sequences.<br />
<br />
== Movie ==<br />
<br />
[[File:3D_movie_met.mov|200px|thumb|left| ]]<br />
'''3D movie showing multiple melanoma brain metastases in a mouse brain'''<br />
<br />
== References ==<br />
<br />
(1) Beadling et al. Clin Cancer Res 2008.<br />
(2) Carvajal et al. JAMA 2011.<br />
(3) Chapman et al. N Engl J Med 2011.<br />
(4) Flaherty et al. N Engl J Med 2010.<br />
(5) Wang et al. Neuropathol Appl Neurobiol 2011.<br />
(6) Bos et al. Nature 2009.<br />
(7) Babic et al. Bioconjug Chem 2008.</div>St03724https://wiki.app.uib.no/mriwiki/index.php?title=Terje_Sundstr%C3%B8m_PhD_project&diff=317Terje Sundstrøm PhD project2011-08-28T20:48:47Z<p>St03724: </p>
<hr />
<div>== '''Molecular biology of melanoma brain metastasis: Potential new therapeutic targets''' ==<br />
<br />
== Terje Sundstrøm ==<br />
<br />
Terje Sundstrøm is a MD from the University of Bergen in 2005, and a resident in neurosurgery at Haukeland University Hospital from 2007. As a medical student he started clinical research in neurosurgery under the supervision of Professor Knut Wester. He has published 8 articles on different neurosurgical topics (http://www.uib.no/persons/Terje.Sundstrom and http://www.neurotrauma.nu). Sundstrøm has during neurosurgical training been recruited to neuro-oncology and translational cancer research. He started his PhD project in January 2011 after being awarded a 3-year scholarship from the Western Norway Regional Health Authority (Helse Vest). His project on melanoma brain metastasis is a part of the Melanoma Metastasis Project headed by Professor Frits Thorsen, Translational Cancer Research Group, Department of Biomedicine, University of Bergen (http://www.uib.no/persons/Frits.Thorsen and https://wikihost.uib.no/mriwiki/index.php/Frits_Thorsen´s_group).<br />
<br />
== Project background ==<br />
<br />
Metastases are responsible for the vast majority of cancer mortality, and brain metastases occur in 1/3 of adults suffering from cancer. Metastases to the brain are 10 times more frequent than primary brain tumors. The number of patients with brain metastases is increasing because treatments for primary cancers are continually improving, and patients are surviving with these diseases longer. The treatment of brain metastases is troublesome and inadequate due to limited effects of cytostatic medications and difficult compromises with respect to consequences of radiation and surgery on surrounding brain structures.<br />
<br />
Melanoma has the highest propensity to metastasize to the brain of all cancers. The median survival time with brain metastases is 6 months. The incidence of melanoma has increased over the last 3 decades, and the death rate continues to rise faster than the rate with most cancers. Recent results have shown that it is possible to develop genetically tailored therapy to various sub-populations of patients with metastatic melanoma ('''1-4''').<br />
<br />
Unfortunately, the mechanisms for metastatic spread of melanoma to the brain are largely unknown. This is due to the lack of relevant in vivo model systems. Patients with brain metastases are often excluded from larger clinical trials, leaving us uncertain about the effect of new therapeutic modalities. New research approaches and treatment strategies are clearly needed to improve the outcome for these patients.<br />
<br />
== Project overview ==<br />
<br />
We have developed competitive animal models to study cancer metastasis and especially to the brain. This project includes extensive use of advanced imaging technology (e.g. 7 Tesla MRI, PET and bioluminescence imaging), as well as state of the art genetic and proteomic analyses through close collaboration with national and international core facilities. Our model system has unique translational possibilities in characterizing cancer metastasis and developing new target specific treatment. Biological and therapeutical considerations have motivated us to study melanoma, but any cancer can in principle be studied.<br />
<br />
In our experimental model, cell lines from human melanoma brain metastases and cell lines from primary, cutaneous melanomas are injected into the left cardiac ventricle of immunodeficient mice. In our spontaneous model, the same cell lines are injected into the skin. We have been able to show that these cells form tumors in the mice, and that the metastatic cell populations more aggressively target the brain. Some of this work has already been published ('''5'''). Preliminary results were recently presented at the AACR in the USA, and as a consequence of this, we are now in the process of establishing a cooperation with the manufacturer of one of the most promising new drugs for metastatic melanoma (Vemurafenib/PLX4032; http://www.plexxikon.com) ('''3''').<br />
<br />
It has previously been shown that breast cancer cells prelabelled with micron-sized iron oxide particles (MPIOs) and thereafter injected intracardially into mice, can be tracked by MRI as single cells in the mouse brain ('''6'''). We are currently doing comprehensive MRI studies to elucidate the metastatic patterns and growth potentials of our cell lines by using a similar particle, called Fedex ('''7'''). This work is done in collaboration with Professor Arvid Lundervold at our department. We are able to visualize single cells labelled with Fedex in the animal brains, and through mathematical modelling we can quantify the brain cell load and follow the development of brain metastases, as well as the interesting aspects of tumor dormancy in the brain. This model system gives us a reliable tool, both quantitatively and qualitatively, to study the efficacy of new treatments.<br />
<br />
We are now working to characterize functional and structural differences in the metastatic patterns of cell lines derived from primary tumors and metastases (e.g. by 7 Tesla MRI, PET and bioluminescence imaging). This work will provides us with a groundwork for a more target specific identification and validation of genetic and epigenetic alterations responsible for melanoma disbursement and growth in the brain. Through functional assessments of candidate genes by overexpression and knockout studies, we hope to contribute to the development of more target specific and effective anti-tumor therapy. We are also in the process of investigating the significance of miRNAs in the metastatic process, by selective insertion of candidate miRNAs into the tumor cells.<br />
<br />
== Figure ==<br />
<br />
[[File:Figure_1.jpg|200px|thumb|left| ]]<br />
'''Modeling melanoma brain metastasis in the mouse'''<br />
A. MRI T1 with contrast 6 weeks after intracardial injection showing a contrast-enhancing tumor in the right hemisphere.<br />
B. 3D brain model of the same animal as in A illustrating multiple metastases.<br />
C. Optical imaging 3 weeks after intracardial injection demonstrating both abdominal and brain tumors.<br />
D. Mathematical modeling with automatic quantification of single Fedex labeled cells in the brain based on MRI T2*/MGE sequences.<br />
<br />
== Movie ==<br />
<br />
[[File:3D_movie_met.mov|200px|thumb|left| ]]<br />
'''3D movie showing multiple melanoma brain metastases in a mouse brain'''<br />
<br />
== References ==<br />
<br />
(1) Beadling et al. Clin Cancer Res 2008.<br />
(2) Carvajal et al. JAMA 2011.<br />
(3) Chapman et al. N Engl J Med 2011.<br />
(4) Flaherty et al. N Engl J Med 2010.<br />
(5) Wang et al. Neuropathol Appl Neurobiol 2011.<br />
(6) Bos et al. Nature 2009.<br />
(7) Babic et al. Bioconjug Chem 2008.</div>St03724https://wiki.app.uib.no/mriwiki/index.php?title=User:St03724&diff=316User:St037242011-08-28T20:46:38Z<p>St03724: moved User:St03724 to Terje Sundstrøms PhD project:&#32;Wanted new name</p>
<hr />
<div>#REDIRECT [[Terje Sundstrøms PhD project]]</div>St03724https://wiki.app.uib.no/mriwiki/index.php?title=Terje_Sundstr%C3%B8m_PhD_project&diff=315Terje Sundstrøm PhD project2011-08-28T20:46:38Z<p>St03724: moved User:St03724 to Terje Sundstrøms PhD project:&#32;Wanted new name</p>
<hr />
<div>== '''Molecular biology of melanoma brain metastasis: Potential new therapeutic targets''' ==<br />
<br />
== Terje Sundstrøm ==<br />
<br />
Terje Sundstrøm is a MD from the University of Bergen in 2005, and a resident in neurosurgery at Haukeland University Hospital from 2007. As a medical student he started clinical research in neurosurgery under the supervision of Professor Knut Wester. He has published 8 articles on different neurosurgical topics (http://www.uib.no/persons/Terje.Sundstrom and http://www.neurotrauma.nu). Sundstrøm has during neurosurgical training been recruited to neuro-oncology and translational cancer research. He started his PhD project in January 2011 after being awarded a 3-year scholarship from the Western Norway Regional Health Authority (Helse Vest). His project on melanoma brain metastasis is a part of the Melanoma Metastasis Project headed by Professor Frits Thorsen, Translational Cancer Research Group, Department of Biomedicine, University of Bergen (http://www.uib.no/persons/Frits.Thorsen).<br />
<br />
== Project background ==<br />
<br />
Metastases are responsible for the vast majority of cancer mortality, and brain metastases occur in 1/3 of adults suffering from cancer. Metastases to the brain are 10 times more frequent than primary brain tumors. The number of patients with brain metastases is increasing because treatments for primary cancers are continually improving, and patients are surviving with these diseases longer. The treatment of brain metastases is troublesome and inadequate due to limited effects of cytostatic medications and difficult compromises with respect to consequences of radiation and surgery on surrounding brain structures.<br />
<br />
Melanoma has the highest propensity to metastasize to the brain of all cancers. The median survival time with brain metastases is 6 months. The incidence of melanoma has increased over the last 3 decades, and the death rate continues to rise faster than the rate with most cancers. Recent results have shown that it is possible to develop genetically tailored therapy to various sub-populations of patients with metastatic melanoma ('''1-4''').<br />
<br />
Unfortunately, the mechanisms for metastatic spread of melanoma to the brain are largely unknown. This is due to the lack of relevant in vivo model systems. Patients with brain metastases are often excluded from larger clinical trials, leaving us uncertain about the effect of new therapeutic modalities. New research approaches and treatment strategies are clearly needed to improve the outcome for these patients.<br />
<br />
== Project overview ==<br />
<br />
We have developed competitive animal models to study cancer metastasis and especially to the brain. This project includes extensive use of advanced imaging technology (e.g. 7 Tesla MRI, PET and bioluminescence imaging), as well as state of the art genetic and proteomic analyses through close collaboration with national and international core facilities. Our model system has unique translational possibilities in characterizing cancer metastasis and developing new target specific treatment. Biological and therapeutical considerations have motivated us to study melanoma, but any cancer can in principle be studied.<br />
<br />
In our experimental model, cell lines from human melanoma brain metastases and cell lines from primary, cutaneous melanomas are injected into the left cardiac ventricle of immunodeficient mice. In our spontaneous model, the same cell lines are injected into the skin. We have been able to show that these cells form tumors in the mice, and that the metastatic cell populations more aggressively target the brain. Some of this work has already been published ('''5'''). Preliminary results were recently presented at the AACR in the USA, and as a consequence of this, we are now in the process of establishing a cooperation with the manufacturer of one of the most promising new drugs for metastatic melanoma (Vemurafenib/PLX4032; http://www.plexxikon.com) ('''3''').<br />
<br />
It has previously been shown that breast cancer cells prelabelled with micron-sized iron oxide particles (MPIOs) and thereafter injected intracardially into mice, can be tracked by MRI as single cells in the mouse brain ('''6'''). We are currently doing comprehensive MRI studies to elucidate the metastatic patterns and growth potentials of our cell lines by using a similar particle, called Fedex ('''7'''). This work is done in collaboration with Professor Arvid Lundervold at our department. We are able to visualize single cells labelled with Fedex in the animal brains, and through mathematical modelling we can quantify the brain cell load and follow the development of brain metastases, as well as the interesting aspects of tumor dormancy in the brain. This model system gives us a reliable tool, both quantitatively and qualitatively, to study the efficacy of new treatments.<br />
<br />
We are now working to characterize functional and structural differences in the metastatic patterns of cell lines derived from primary tumors and metastases (e.g. by 7 Tesla MRI, PET and bioluminescence imaging). This work will provides us with a groundwork for a more target specific identification and validation of genetic and epigenetic alterations responsible for melanoma disbursement and growth in the brain. Through functional assessments of candidate genes by overexpression and knockout studies, we hope to contribute to the development of more target specific and effective anti-tumor therapy. We are also in the process of investigating the significance of miRNAs in the metastatic process, by selective insertion of candidate miRNAs into the tumor cells.<br />
<br />
== Figure ==<br />
<br />
[[File:Figure_1.jpg|200px|thumb|left| ]]<br />
'''Modeling melanoma brain metastasis in the mouse'''<br />
A. MRI T1 with contrast 6 weeks after intracardial injection showing a contrast-enhancing tumor in the right hemisphere.<br />
B. 3D brain model of the same animal as in A illustrating multiple metastases.<br />
C. Optical imaging 3 weeks after intracardial injection demonstrating both abdominal and brain tumors.<br />
D. Mathematical modeling with automatic quantification of single Fedex labeled cells in the brain based on MRI T2*/MGE sequences.<br />
<br />
== Movie ==<br />
<br />
[[File:3D_movie_met.mov|200px|thumb|left| ]]<br />
'''3D movie showing multiple melanoma brain metastases in a mouse brain'''<br />
<br />
== References ==<br />
<br />
(1) Beadling et al. Clin Cancer Res 2008.<br />
(2) Carvajal et al. JAMA 2011.<br />
(3) Chapman et al. N Engl J Med 2011.<br />
(4) Flaherty et al. N Engl J Med 2010.<br />
(5) Wang et al. Neuropathol Appl Neurobiol 2011.<br />
(6) Bos et al. Nature 2009.<br />
(7) Babic et al. Bioconjug Chem 2008.</div>St03724https://wiki.app.uib.no/mriwiki/index.php?title=Terje_Sundstr%C3%B8m_PhD_project&diff=314Terje Sundstrøm PhD project2011-08-28T20:43:50Z<p>St03724: </p>
<hr />
<div>== '''Molecular biology of melanoma brain metastasis: Potential new therapeutic targets''' ==<br />
<br />
== Terje Sundstrøm ==<br />
<br />
Terje Sundstrøm is a MD from the University of Bergen in 2005, and a resident in neurosurgery at Haukeland University Hospital from 2007. As a medical student he started clinical research in neurosurgery under the supervision of Professor Knut Wester. He has published 8 articles on different neurosurgical topics (http://www.uib.no/persons/Terje.Sundstrom and http://www.neurotrauma.nu). Sundstrøm has during neurosurgical training been recruited to neuro-oncology and translational cancer research. He started his PhD project in January 2011 after being awarded a 3-year scholarship from the Western Norway Regional Health Authority (Helse Vest). His project on melanoma brain metastasis is a part of the Melanoma Metastasis Project headed by Professor Frits Thorsen, Translational Cancer Research Group, Department of Biomedicine, University of Bergen (http://www.uib.no/persons/Frits.Thorsen).<br />
<br />
== Project background ==<br />
<br />
Metastases are responsible for the vast majority of cancer mortality, and brain metastases occur in 1/3 of adults suffering from cancer. Metastases to the brain are 10 times more frequent than primary brain tumors. The number of patients with brain metastases is increasing because treatments for primary cancers are continually improving, and patients are surviving with these diseases longer. The treatment of brain metastases is troublesome and inadequate due to limited effects of cytostatic medications and difficult compromises with respect to consequences of radiation and surgery on surrounding brain structures.<br />
<br />
Melanoma has the highest propensity to metastasize to the brain of all cancers. The median survival time with brain metastases is 6 months. The incidence of melanoma has increased over the last 3 decades, and the death rate continues to rise faster than the rate with most cancers. Recent results have shown that it is possible to develop genetically tailored therapy to various sub-populations of patients with metastatic melanoma ('''1-4''').<br />
<br />
Unfortunately, the mechanisms for metastatic spread of melanoma to the brain are largely unknown. This is due to the lack of relevant in vivo model systems. Patients with brain metastases are often excluded from larger clinical trials, leaving us uncertain about the effect of new therapeutic modalities. New research approaches and treatment strategies are clearly needed to improve the outcome for these patients.<br />
<br />
== Project overview ==<br />
<br />
We have developed competitive animal models to study cancer metastasis and especially to the brain. This project includes extensive use of advanced imaging technology (e.g. 7 Tesla MRI, PET and bioluminescence imaging), as well as state of the art genetic and proteomic analyses through close collaboration with national and international core facilities. Our model system has unique translational possibilities in characterizing cancer metastasis and developing new target specific treatment. Biological and therapeutical considerations have motivated us to study melanoma, but any cancer can in principle be studied.<br />
<br />
In our experimental model, cell lines from human melanoma brain metastases and cell lines from primary, cutaneous melanomas are injected into the left cardiac ventricle of immunodeficient mice. In our spontaneous model, the same cell lines are injected into the skin. We have been able to show that these cells form tumors in the mice, and that the metastatic cell populations more aggressively target the brain. Some of this work has already been published ('''5'''). Preliminary results were recently presented at the AACR in the USA, and as a consequence of this, we are now in the process of establishing a cooperation with the manufacturer of one of the most promising new drugs for metastatic melanoma (Vemurafenib/PLX4032; http://www.plexxikon.com) ('''3''').<br />
<br />
It has previously been shown that breast cancer cells prelabelled with micron-sized iron oxide particles (MPIOs) and thereafter injected intracardially into mice, can be tracked by MRI as single cells in the mouse brain ('''6'''). We are currently doing comprehensive MRI studies to elucidate the metastatic patterns and growth potentials of our cell lines by using a similar particle, called Fedex ('''7'''). This work is done in collaboration with Professor Arvid Lundervold at our department. We are able to visualize single cells labelled with Fedex in the animal brains, and through mathematical modelling we can quantify the brain cell load and follow the development of brain metastases, as well as the interesting aspects of tumor dormancy in the brain. This model system gives us a reliable tool, both quantitatively and qualitatively, to study the efficacy of new treatments.<br />
<br />
We are now working to characterize functional and structural differences in the metastatic patterns of cell lines derived from primary tumors and metastases (e.g. by 7 Tesla MRI, PET and bioluminescence imaging). This work will provides us with a groundwork for a more target specific identification and validation of genetic and epigenetic alterations responsible for melanoma disbursement and growth in the brain. Through functional assessments of candidate genes by overexpression and knockout studies, we hope to contribute to the development of more target specific and effective anti-tumor therapy. We are also in the process of investigating the significance of miRNAs in the metastatic process, by selective insertion of candidate miRNAs into the tumor cells.<br />
<br />
== Figure ==<br />
<br />
[[File:Figure_1.jpg|200px|thumb|left| ]]<br />
'''Modeling melanoma brain metastasis in the mouse'''<br />
A. MRI T1 with contrast 6 weeks after intracardial injection showing a contrast-enhancing tumor in the right hemisphere.<br />
B. 3D brain model of the same animal as in A illustrating multiple metastases.<br />
C. Optical imaging 3 weeks after intracardial injection demonstrating both abdominal and brain tumors.<br />
D. Mathematical modeling with automatic quantification of single Fedex labeled cells in the brain based on MRI T2*/MGE sequences.<br />
<br />
== Movie ==<br />
<br />
[[File:3D_movie_met.mov|200px|thumb|left| ]]<br />
'''3D movie showing multiple melanoma brain metastases in a mouse brain'''<br />
<br />
== References ==<br />
<br />
(1) Beadling et al. Clin Cancer Res 2008.<br />
(2) Carvajal et al. JAMA 2011.<br />
(3) Chapman et al. N Engl J Med 2011.<br />
(4) Flaherty et al. N Engl J Med 2010.<br />
(5) Wang et al. Neuropathol Appl Neurobiol 2011.<br />
(6) Bos et al. Nature 2009.<br />
(7) Babic et al. Bioconjug Chem 2008.</div>St03724https://wiki.app.uib.no/mriwiki/index.php?title=Terje_Sundstr%C3%B8m_PhD_project&diff=313Terje Sundstrøm PhD project2011-08-28T20:43:23Z<p>St03724: </p>
<hr />
<div>== '''Molecular biology of melanoma brain metastasis: Potential new therapeutic targets''' ==<br />
<br />
== Terje Sundstrøm ==<br />
<br />
Terje Sundstrøm is a MD from the University of Bergen in 2005, and a resident in neurosurgery at Haukeland University Hospital from 2007. As a medical student he started clinical research in neurosurgery under the supervision of Professor Knut Wester. He has published 8 articles on different neurosurgical topics (http://www.uib.no/persons/Terje.Sundstrom and [http://www.neurotrauma.nu]). Sundstrøm has during neurosurgical training been recruited to neuro-oncology and translational cancer research. He started his PhD project in January 2011 after being awarded a 3-year scholarship from the Western Norway Regional Health Authority (Helse Vest). His project on melanoma brain metastasis is a part of the Melanoma Metastasis Project headed by Professor Frits Thorsen, Translational Cancer Research Group, Department of Biomedicine, University of Bergen (http://www.uib.no/persons/Frits.Thorsen).<br />
<br />
== Project background ==<br />
<br />
Metastases are responsible for the vast majority of cancer mortality, and brain metastases occur in 1/3 of adults suffering from cancer. Metastases to the brain are 10 times more frequent than primary brain tumors. The number of patients with brain metastases is increasing because treatments for primary cancers are continually improving, and patients are surviving with these diseases longer. The treatment of brain metastases is troublesome and inadequate due to limited effects of cytostatic medications and difficult compromises with respect to consequences of radiation and surgery on surrounding brain structures.<br />
<br />
Melanoma has the highest propensity to metastasize to the brain of all cancers. The median survival time with brain metastases is 6 months. The incidence of melanoma has increased over the last 3 decades, and the death rate continues to rise faster than the rate with most cancers. Recent results have shown that it is possible to develop genetically tailored therapy to various sub-populations of patients with metastatic melanoma ('''1-4''').<br />
<br />
Unfortunately, the mechanisms for metastatic spread of melanoma to the brain are largely unknown. This is due to the lack of relevant in vivo model systems. Patients with brain metastases are often excluded from larger clinical trials, leaving us uncertain about the effect of new therapeutic modalities. New research approaches and treatment strategies are clearly needed to improve the outcome for these patients.<br />
<br />
== Project overview ==<br />
<br />
We have developed competitive animal models to study cancer metastasis and especially to the brain. This project includes extensive use of advanced imaging technology (e.g. 7 Tesla MRI, PET and bioluminescence imaging), as well as state of the art genetic and proteomic analyses through close collaboration with national and international core facilities. Our model system has unique translational possibilities in characterizing cancer metastasis and developing new target specific treatment. Biological and therapeutical considerations have motivated us to study melanoma, but any cancer can in principle be studied.<br />
<br />
In our experimental model, cell lines from human melanoma brain metastases and cell lines from primary, cutaneous melanomas are injected into the left cardiac ventricle of immunodeficient mice. In our spontaneous model, the same cell lines are injected into the skin. We have been able to show that these cells form tumors in the mice, and that the metastatic cell populations more aggressively target the brain. Some of this work has already been published ('''5'''). Preliminary results were recently presented at the AACR in the USA, and as a consequence of this, we are now in the process of establishing a cooperation with the manufacturer of one of the most promising new drugs for metastatic melanoma (Vemurafenib/PLX4032; http://www.plexxikon.com) ('''3''').<br />
<br />
It has previously been shown that breast cancer cells prelabelled with micron-sized iron oxide particles (MPIOs) and thereafter injected intracardially into mice, can be tracked by MRI as single cells in the mouse brain ('''6'''). We are currently doing comprehensive MRI studies to elucidate the metastatic patterns and growth potentials of our cell lines by using a similar particle, called Fedex ('''7'''). This work is done in collaboration with Professor Arvid Lundervold at our department. We are able to visualize single cells labelled with Fedex in the animal brains, and through mathematical modelling we can quantify the brain cell load and follow the development of brain metastases, as well as the interesting aspects of tumor dormancy in the brain. This model system gives us a reliable tool, both quantitatively and qualitatively, to study the efficacy of new treatments.<br />
<br />
We are now working to characterize functional and structural differences in the metastatic patterns of cell lines derived from primary tumors and metastases (e.g. by 7 Tesla MRI, PET and bioluminescence imaging). This work will provides us with a groundwork for a more target specific identification and validation of genetic and epigenetic alterations responsible for melanoma disbursement and growth in the brain. Through functional assessments of candidate genes by overexpression and knockout studies, we hope to contribute to the development of more target specific and effective anti-tumor therapy. We are also in the process of investigating the significance of miRNAs in the metastatic process, by selective insertion of candidate miRNAs into the tumor cells.<br />
<br />
== Figure ==<br />
<br />
[[File:Figure_1.jpg|200px|thumb|left| ]]<br />
'''Modeling melanoma brain metastasis in the mouse'''<br />
A. MRI T1 with contrast 6 weeks after intracardial injection showing a contrast-enhancing tumor in the right hemisphere.<br />
B. 3D brain model of the same animal as in A illustrating multiple metastases.<br />
C. Optical imaging 3 weeks after intracardial injection demonstrating both abdominal and brain tumors.<br />
D. Mathematical modeling with automatic quantification of single Fedex labeled cells in the brain based on MRI T2*/MGE sequences.<br />
<br />
== Movie ==<br />
<br />
[[File:3D_movie_met.mov|200px|thumb|left| ]]<br />
'''3D movie showing multiple melanoma brain metastases in a mouse brain'''<br />
<br />
== References ==<br />
<br />
(1) Beadling et al. Clin Cancer Res 2008.<br />
(2) Carvajal et al. JAMA 2011.<br />
(3) Chapman et al. N Engl J Med 2011.<br />
(4) Flaherty et al. N Engl J Med 2010.<br />
(5) Wang et al. Neuropathol Appl Neurobiol 2011.<br />
(6) Bos et al. Nature 2009.<br />
(7) Babic et al. Bioconjug Chem 2008.</div>St03724https://wiki.app.uib.no/mriwiki/index.php?title=Terje_Sundstr%C3%B8m_PhD_project&diff=312Terje Sundstrøm PhD project2011-08-28T20:42:18Z<p>St03724: </p>
<hr />
<div>== '''Molecular biology of melanoma brain metastasis: Potential new therapeutic targets''' ==<br />
<br />
== Terje Sundstrøm ==<br />
<br />
Terje Sundstrøm is a MD from the University of Bergen in 2005, and a resident in neurosurgery at Haukeland University Hospital from 2007. As a medical student he started clinical research in neurosurgery under the supervision of Professor Knut Wester. He has published 8 articles on different neurosurgical topics (http://www.uib.no/persons/Terje.Sundstrom). Sundstrøm has during neurosurgical training been recruited to neuro-oncology and translational cancer research. He started his PhD project in January 2011 after being awarded a 3-year scholarship from the Western Norway Regional Health Authority (Helse Vest). His project on melanoma brain metastasis is a part of the Melanoma Metastasis Project headed by Professor Frits Thorsen, Translational Cancer Research Group, Department of Biomedicine, University of Bergen (http://www.uib.no/persons/Frits.Thorsen).<br />
<br />
== Project background ==<br />
<br />
Metastases are responsible for the vast majority of cancer mortality, and brain metastases occur in 1/3 of adults suffering from cancer. Metastases to the brain are 10 times more frequent than primary brain tumors. The number of patients with brain metastases is increasing because treatments for primary cancers are continually improving, and patients are surviving with these diseases longer. The treatment of brain metastases is troublesome and inadequate due to limited effects of cytostatic medications and difficult compromises with respect to consequences of radiation and surgery on surrounding brain structures.<br />
<br />
Melanoma has the highest propensity to metastasize to the brain of all cancers. The median survival time with brain metastases is 6 months. The incidence of melanoma has increased over the last 3 decades, and the death rate continues to rise faster than the rate with most cancers. Recent results have shown that it is possible to develop genetically tailored therapy to various sub-populations of patients with metastatic melanoma ('''1-4''').<br />
<br />
Unfortunately, the mechanisms for metastatic spread of melanoma to the brain are largely unknown. This is due to the lack of relevant in vivo model systems. Patients with brain metastases are often excluded from larger clinical trials, leaving us uncertain about the effect of new therapeutic modalities. New research approaches and treatment strategies are clearly needed to improve the outcome for these patients.<br />
<br />
== Project overview ==<br />
<br />
We have developed competitive animal models to study cancer metastasis and especially to the brain. This project includes extensive use of advanced imaging technology (e.g. 7 Tesla MRI, PET and bioluminescence imaging), as well as state of the art genetic and proteomic analyses through close collaboration with national and international core facilities. Our model system has unique translational possibilities in characterizing cancer metastasis and developing new target specific treatment. Biological and therapeutical considerations have motivated us to study melanoma, but any cancer can in principle be studied.<br />
<br />
In our experimental model, cell lines from human melanoma brain metastases and cell lines from primary, cutaneous melanomas are injected into the left cardiac ventricle of immunodeficient mice. In our spontaneous model, the same cell lines are injected into the skin. We have been able to show that these cells form tumors in the mice, and that the metastatic cell populations more aggressively target the brain. Some of this work has already been published ('''5'''). Preliminary results were recently presented at the AACR in the USA, and as a consequence of this, we are now in the process of establishing a cooperation with the manufacturer of one of the most promising new drugs for metastatic melanoma (Vemurafenib/PLX4032; http://www.plexxikon.com) ('''3''').<br />
<br />
It has previously been shown that breast cancer cells prelabelled with micron-sized iron oxide particles (MPIOs) and thereafter injected intracardially into mice, can be tracked by MRI as single cells in the mouse brain ('''6'''). We are currently doing comprehensive MRI studies to elucidate the metastatic patterns and growth potentials of our cell lines by using a similar particle, called Fedex ('''7'''). This work is done in collaboration with Professor Arvid Lundervold at our department. We are able to visualize single cells labelled with Fedex in the animal brains, and through mathematical modelling we can quantify the brain cell load and follow the development of brain metastases, as well as the interesting aspects of tumor dormancy in the brain. This model system gives us a reliable tool, both quantitatively and qualitatively, to study the efficacy of new treatments.<br />
<br />
We are now working to characterize functional and structural differences in the metastatic patterns of cell lines derived from primary tumors and metastases (e.g. by 7 Tesla MRI, PET and bioluminescence imaging). This work will provides us with a groundwork for a more target specific identification and validation of genetic and epigenetic alterations responsible for melanoma disbursement and growth in the brain. Through functional assessments of candidate genes by overexpression and knockout studies, we hope to contribute to the development of more target specific and effective anti-tumor therapy. We are also in the process of investigating the significance of miRNAs in the metastatic process, by selective insertion of candidate miRNAs into the tumor cells.<br />
<br />
== Figure ==<br />
<br />
[[File:Figure_1.jpg|200px|thumb|left| ]]<br />
'''Modeling melanoma brain metastasis in the mouse'''<br />
A. MRI T1 with contrast 6 weeks after intracardial injection showing a contrast-enhancing tumor in the right hemisphere.<br />
B. 3D brain model of the same animal as in A illustrating multiple metastases.<br />
C. Optical imaging 3 weeks after intracardial injection demonstrating both abdominal and brain tumors.<br />
D. Mathematical modeling with automatic quantification of single Fedex labeled cells in the brain based on MRI T2*/MGE sequences.<br />
<br />
== Movie ==<br />
<br />
[[File:3D_movie_met.mov|200px|thumb|left| ]]<br />
'''3D movie showing multiple melanoma brain metastases in a mouse brain'''<br />
<br />
== References ==<br />
<br />
(1) Beadling et al. Clin Cancer Res 2008.<br />
(2) Carvajal et al. JAMA 2011.<br />
(3) Chapman et al. N Engl J Med 2011.<br />
(4) Flaherty et al. N Engl J Med 2010.<br />
(5) Wang et al. Neuropathol Appl Neurobiol 2011.<br />
(6) Bos et al. Nature 2009.<br />
(7) Babic et al. Bioconjug Chem 2008.</div>St03724https://wiki.app.uib.no/mriwiki/index.php?title=Terje_Sundstr%C3%B8m_PhD_project&diff=311Terje Sundstrøm PhD project2011-08-28T20:39:00Z<p>St03724: </p>
<hr />
<div>== '''Molecular biology of melanoma brain metastasis: Potential new therapeutic targets''' ==<br />
<br />
== Terje Sundstrøm ==<br />
<br />
Terje Sundstrøm is a MD from the University of Bergen in 2005, and a resident in neurosurgery at Haukeland University Hospital from 2007. As a medical student he started clinical research in neurosurgery. His efforts have so far generated 8 publications on different neurosurgical topics (http://www.uib.no/persons/Terje.Sundstrom). Sundstrøm has during neurosurgical training been recruited to neuro-oncology and translational cancer research. He started his PhD project in January 2011 after receiving a 3-year scholarship from the Western Norway Regional Health Authority. His project on melanoma brain metastasis is a part of the Melanoma Metastasis Project headed by Professor Frits Thorsen, Translational Cancer Research Group, Department of Biomedicine, University of Bergen (http://www.uib.no/persons/Frits.Thorsen).<br />
<br />
== Project background ==<br />
<br />
Metastases are responsible for the vast majority of cancer mortality, and brain metastases occur in 1/3 of adults suffering from cancer. Metastases to the brain are 10 times more frequent than primary brain tumors. The number of patients with brain metastases is increasing because treatments for primary cancers are continually improving, and patients are surviving with these diseases longer. The treatment of brain metastases is troublesome and inadequate due to limited effects of cytostatic medications and difficult compromises with respect to consequences of radiation and surgery on surrounding brain structures.<br />
<br />
Melanoma has the highest propensity to metastasize to the brain of all cancers. The median survival time with brain metastases is 6 months. The incidence of melanoma has increased over the last 3 decades, and the death rate continues to rise faster than the rate with most cancers. Recent results have shown that it is possible to develop genetically tailored therapy to various sub-populations of patients with metastatic melanoma ('''1-4''').<br />
<br />
Unfortunately, the mechanisms for metastatic spread of melanoma to the brain are largely unknown. This is due to the lack of relevant in vivo model systems. Patients with brain metastases are often excluded from larger clinical trials, leaving us uncertain about the effect of new therapeutic modalities. New research approaches and treatment strategies are clearly needed to improve the outcome for these patients.<br />
<br />
== Project overview ==<br />
<br />
We have developed competitive animal models to study cancer metastasis and especially to the brain. This project includes extensive use of advanced imaging technology (e.g. 7 Tesla MRI, PET and bioluminescence imaging), as well as state of the art genetic and proteomic analyses through close collaboration with national and international core facilities. Our model system has unique translational possibilities in characterizing cancer metastasis and developing new target specific treatment. Biological and therapeutical considerations have motivated us to study melanoma, but any cancer can in principle be studied.<br />
<br />
In our experimental model, cell lines from human melanoma brain metastases and cell lines from primary, cutaneous melanomas are injected into the left cardiac ventricle of immunodeficient mice. In our spontaneous model, the same cell lines are injected into the skin. We have been able to show that these cells form tumors in the mice, and that the metastatic cell populations more aggressively target the brain. Some of this work has already been published ('''5'''). Preliminary results were recently presented at the AACR in the USA, and as a consequence of this, we are now in the process of establishing a cooperation with the manufacturer of one of the most promising new drugs for metastatic melanoma (Vemurafenib/PLX4032; http://www.plexxikon.com) ('''3''').<br />
<br />
It has previously been shown that breast cancer cells prelabelled with micron-sized iron oxide particles (MPIOs) and thereafter injected intracardially into mice, can be tracked by MRI as single cells in the mouse brain ('''6'''). We are currently doing comprehensive MRI studies to elucidate the metastatic patterns and growth potentials of our cell lines by using a similar particle, called Fedex ('''7'''). This work is done in collaboration with Professor Arvid Lundervold at our department. We are able to visualize single cells labelled with Fedex in the animal brains, and through mathematical modelling we can quantify the brain cell load and follow the development of brain metastases, as well as the interesting aspects of tumor dormancy in the brain. This model system gives us a reliable tool, both quantitatively and qualitatively, to study the efficacy of new treatments.<br />
<br />
We are now working to characterize functional and structural differences in the metastatic patterns of cell lines derived from primary tumors and metastases (e.g. by 7 Tesla MRI, PET and bioluminescence imaging). This work will provides us with a groundwork for a more target specific identification and validation of genetic and epigenetic alterations responsible for melanoma disbursement and growth in the brain. Through functional assessments of candidate genes by overexpression and knockout studies, we hope to contribute to the development of more target specific and effective anti-tumor therapy. We are also in the process of investigating the significance of miRNAs in the metastatic process, by selective insertion of candidate miRNAs into the tumor cells.<br />
<br />
== Figure ==<br />
<br />
[[File:Figure_1.jpg|200px|thumb|left| ]]<br />
'''Modeling melanoma brain metastasis in the mouse'''<br />
A. MRI T1 with contrast 6 weeks after intracardial injection showing a contrast-enhancing tumor in the right hemisphere.<br />
B. 3D brain model of the same animal as in A illustrating multiple metastases.<br />
C. Optical imaging 3 weeks after intracardial injection demonstrating both abdominal and brain tumors.<br />
D. Mathematical modeling with automatic quantification of single Fedex labeled cells in the brain based on MRI T2*/MGE sequences.<br />
<br />
== Movie ==<br />
<br />
[[File:3D_movie_met.mov|200px|thumb|left| ]]<br />
'''3D movie showing multiple melanoma brain metastases in a mouse brain'''<br />
<br />
== References ==<br />
<br />
(1) Beadling et al. Clin Cancer Res 2008.<br />
(2) Carvajal et al. JAMA 2011.<br />
(3) Chapman et al. N Engl J Med 2011.<br />
(4) Flaherty et al. N Engl J Med 2010.<br />
(5) Wang et al. Neuropathol Appl Neurobiol 2011.<br />
(6) Bos et al. Nature 2009.<br />
(7) Babic et al. Bioconjug Chem 2008.</div>St03724https://wiki.app.uib.no/mriwiki/index.php?title=Terje_Sundstr%C3%B8m_PhD_project&diff=310Terje Sundstrøm PhD project2011-08-28T20:37:41Z<p>St03724: </p>
<hr />
<div>== '''Molecular biology of melanoma brain metastasis: Potential new therapeutic targets''' ==<br />
<br />
== Terje Sundstrøm ==<br />
<br />
Terje Sundstrøm is a MD from the University of Bergen in 2005, and a resident in neurosurgery at Haukeland University Hospital from 2007. As a medical student he started clinical research in neurosurgery. His efforts have so far generated 8 publications on different neurosurgical topics (http://www.uib.no/persons/Terje.Sundstrom). Sundstrøm has during neurosurgical training been recruited to neuro-oncology and translational cancer research. He started his PhD project in January 2011 after receiving a 3-year scholarship from the Western Norway Regional Health Authority. His project on melanoma brain metastasis is a part of the Melanoma Metastasis Project headed by Professor Frits Thorsen, Translational Cancer Research Group, Department of Biomedicine, University of Bergen (http://www.uib.no/persons/Frits.Thorsen).<br />
<br />
== Project background ==<br />
<br />
Metastases are responsible for the vast majority of cancer mortality, and brain metastases occur in 1/3 of adults suffering from cancer. Metastases to the brain are 10 times more frequent than primary brain tumors. The number of patients with brain metastases is increasing because treatments for primary cancers are continually improving, and patients are surviving with these diseases longer. The treatment of brain metastases is troublesome and inadequate due to limited effects of cytostatic medications and difficult compromises with respect to consequences of radiation and surgery on surrounding brain structures.<br />
<br />
Melanoma has the highest propensity to metastasize to the brain of all cancers. The median survival time with brain metastases is 6 months. The incidence of melanoma has increased over the last 3 decades, and the death rate continues to rise faster than the rate with most cancers. Recent results have shown that it is possible to develop genetically tailored therapy to various sub-populations of patients with metastatic melanoma ('''1-4''').<br />
<br />
Unfortunately, the mechanisms for metastatic spread of melanoma to the brain are largely unknown. This is due to the lack of relevant in vivo model systems. Patients with brain metastases are often excluded from larger clinical trials, leaving us uncertain about the effect of new therapeutic modalities. New research approaches and treatment strategies are clearly needed to improve the outcome for these patients.<br />
<br />
== Project overview ==<br />
<br />
We have developed competitive animal models to study cancer metastasis and especially to the brain. This project includes extensive use of advanced imaging technology (e.g. 7 Tesla MRI, PET and bioluminescence imaging), as well as state of the art genetic and proteomic analyses through close collaboration with national and international core facilities. Our model system has unique translational possibilities in characterizing cancer metastasis and developing new target specific treatment. Biological and therapeutical considerations have motivated us to study melanoma, but any cancer can in principle be studied.<br />
<br />
In our experimental model, cell lines from human melanoma brain metastases and cell lines from primary, cutaneous melanomas are injected into the left cardiac ventricle of immunodeficient mice. In our spontaneous model, the same cell lines are injected into the skin. We have been able to show that these cells form tumors in the mice, and that the metastatic cell populations more aggressively target the brain. Some of this work has already been published ('''5'''). Preliminary results were recently presented at the AACR in the USA, and as a consequence of this, we are now in the process of establishing a cooperation with the manufacturer of one of the most promising new drugs for metastatic melanoma (Vemurafenib/PLX4032; http://www.plexxikon.com) ('''3''').<br />
<br />
It has previously been shown that breast cancer cells prelabelled with micron-sized iron oxide particles (MPIOs) and thereafter injected intracardially into mice, can be tracked by MRI as single cells in the mouse brain ('''6'''). We are currently doing comprehensive MRI studies to elucidate the metastatic patterns and growth potentials of our cell lines by using a similar particle, called Fedex ('''7'''). This work is done in collaboration with Professor Arvid Lundervold at our department. We are able to visualize single cells labelled with Fedex in the animal brains, and through mathematical modelling we can quantify the brain cell load and follow the development of brain metastases, as well as the interesting aspects of tumor dormancy in the brain. This model system gives us a reliable tool, both quantitatively and qualitatively, to study the efficacy of new treatments.<br />
<br />
We are now working to characterize functional and structural differences in the metastatic patterns of cell lines derived from primary tumors and metastases (e.g. by 7 Tesla MRI, PET and bioluminescence imaging). This work will provides us with a groundwork for a more target specific identification and validation of genetic and epigenetic alterations responsible for melanoma disbursement and growth in the brain. Through functional assessments of candidate genes by overexpression and knockout studies, we hope to contribute to the development of more target specific and effective anti-tumor therapy. We are also in the process of investigating the significance of miRNAs in the metastatic process, by selective insertion of candidate miRNAs into the tumor cells.<br />
<br />
== Figure ==<br />
<br />
[[File:Figure_1.jpg|200px|thumb|left|'''Modeling melanoma brain metastasis in the mouse'''<br />
A. MRI T1 with contrast 6 weeks after intracardial injection showing a contrast-enhancing tumor in the right hemisphere.<br />
B. 3D brain model of the same animal as in A illustrating multiple metastases.<br />
C. Optical imaging 3 weeks after intracardial injection demonstrating both abdominal and brain tumors.<br />
D. Mathematical modeling with automatic quantification of single Fedex labeled cells in the brain based on MRI T2*/MGE sequences.]]<br />
<br />
== Movie ==<br />
<br />
[[File:3D_movie_met.mov|200px|thumb|left|alt text]]<br />
'''3D movie showing multiple melanoma brain metastases in a mouse brain'''<br />
<br />
== References ==<br />
<br />
(1) Beadling et al. Clin Cancer Res 2008.<br />
(2) Carvajal et al. JAMA 2011.<br />
(3) Chapman et al. N Engl J Med 2011.<br />
(4) Flaherty et al. N Engl J Med 2010.<br />
(5) Wang et al. Neuropathol Appl Neurobiol 2011.<br />
(6) Bos et al. Nature 2009.<br />
(7) Babic et al. Bioconjug Chem 2008.</div>St03724https://wiki.app.uib.no/mriwiki/index.php?title=Terje_Sundstr%C3%B8m_PhD_project&diff=309Terje Sundstrøm PhD project2011-08-28T20:35:52Z<p>St03724: </p>
<hr />
<div>== '''Molecular biology of melanoma brain metastasis: Potential new therapeutic targets''' ==<br />
<br />
== Terje Sundstrøm ==<br />
<br />
Terje Sundstrøm is a MD from the University of Bergen in 2005, and a resident in neurosurgery at Haukeland University Hospital from 2007. As a medical student he started clinical research in neurosurgery. His efforts have so far generated 8 publications on different neurosurgical topics (http://www.uib.no/persons/Terje.Sundstrom). Sundstrøm has during neurosurgical training been recruited to neuro-oncology and translational cancer research. He started his PhD project in January 2011 after receiving a 3-year scholarship from the Western Norway Regional Health Authority. His project on melanoma brain metastasis is a part of the Melanoma Metastasis Project headed by Professor Frits Thorsen, Translational Cancer Research Group, Department of Biomedicine, University of Bergen (http://www.uib.no/persons/Frits.Thorsen).<br />
<br />
== Project background ==<br />
<br />
Metastases are responsible for the vast majority of cancer mortality, and brain metastases occur in 1/3 of adults suffering from cancer. Metastases to the brain are 10 times more frequent than primary brain tumors. The number of patients with brain metastases is increasing because treatments for primary cancers are continually improving, and patients are surviving with these diseases longer. The treatment of brain metastases is troublesome and inadequate due to limited effects of cytostatic medications and difficult compromises with respect to consequences of radiation and surgery on surrounding brain structures.<br />
<br />
Melanoma has the highest propensity to metastasize to the brain of all cancers. The median survival time with brain metastases is 6 months. The incidence of melanoma has increased over the last 3 decades, and the death rate continues to rise faster than the rate with most cancers. Recent results have shown that it is possible to develop genetically tailored therapy to various sub-populations of patients with metastatic melanoma ('''1-4''').<br />
<br />
Unfortunately, the mechanisms for metastatic spread of melanoma to the brain are largely unknown. This is due to the lack of relevant in vivo model systems. Patients with brain metastases are often excluded from larger clinical trials, leaving us uncertain about the effect of new therapeutic modalities. New research approaches and treatment strategies are clearly needed to improve the outcome for these patients.<br />
<br />
== Project overview ==<br />
<br />
We have developed competitive animal models to study cancer metastasis and especially to the brain. This project includes extensive use of advanced imaging technology (e.g. 7 Tesla MRI, PET and bioluminescence imaging), as well as state of the art genetic and proteomic analyses through close collaboration with national and international core facilities. Our model system has unique translational possibilities in characterizing cancer metastasis and developing new target specific treatment. Biological and therapeutical considerations have motivated us to study melanoma, but any cancer can in principle be studied.<br />
<br />
In our experimental model, cell lines from human melanoma brain metastases and cell lines from primary, cutaneous melanomas are injected into the left cardiac ventricle of immunodeficient mice. In our spontaneous model, the same cell lines are injected into the skin. We have been able to show that these cells form tumors in the mice, and that the metastatic cell populations more aggressively target the brain. Some of this work has already been published ('''5'''). Preliminary results were recently presented at the AACR in the USA, and as a consequence of this, we are now in the process of establishing a cooperation with the manufacturer of one of the most promising new drugs for metastatic melanoma (Vemurafenib/PLX4032; http://www.plexxikon.com) ('''3''').<br />
<br />
It has previously been shown that breast cancer cells prelabelled with micron-sized iron oxide particles (MPIOs) and thereafter injected intracardially into mice, can be tracked by MRI as single cells in the mouse brain ('''6'''). We are currently doing comprehensive MRI studies to elucidate the metastatic patterns and growth potentials of our cell lines by using a similar particle, called Fedex ('''7'''). This work is done in collaboration with Professor Arvid Lundervold at our department. We are able to visualize single cells labelled with Fedex in the animal brains, and through mathematical modelling we can quantify the brain cell load and follow the development of brain metastases, as well as the interesting aspects of tumor dormancy in the brain. This model system gives us a reliable tool, both quantitatively and qualitatively, to study the efficacy of new treatments.<br />
<br />
We are now working to characterize functional and structural differences in the metastatic patterns of cell lines derived from primary tumors and metastases (e.g. by 7 Tesla MRI, PET and bioluminescence imaging). This work will provides us with a groundwork for a more target specific identification and validation of genetic and epigenetic alterations responsible for melanoma disbursement and growth in the brain. Through functional assessments of candidate genes by overexpression and knockout studies, we hope to contribute to the development of more target specific and effective anti-tumor therapy. We are also in the process of investigating the significance of miRNAs in the metastatic process, by selective insertion of candidate miRNAs into the tumor cells.<br />
<br />
== Figure ==<br />
<br />
[[File:Figure_1.jpg|200px|thumb|left|'''Modeling melanoma brain metastasis in the mouse'''<br />
A. MRI T1 with contrast 6 weeks after intracardial injection showing a contrast-enhancing tumor in the right hemisphere.<br />
B. 3D brain model of the same animal as in A illustrating multiple metastases.<br />
C. Optical imaging 3 weeks after intracardial injection demonstrating both abdominal and brain tumors.<br />
D. Mathematical modeling with automatic quantification of single Fedex labeled cells in the brain based on MRI T2*/MGE sequences.]]<br />
<br />
== Movie ==<br />
<br />
[[File:3D_movie_met.mov]]<br />
<br />
[[File:3D_movie_met.mov|200px|thumb|left|'''3D movie showing multiple melanoma brain metastases in a mouse brain''']]<br />
<br />
== References ==<br />
<br />
(1) Beadling et al. Clin Cancer Res 2008.<br />
(2) Carvajal et al. JAMA 2011.<br />
(3) Chapman et al. N Engl J Med 2011.<br />
(4) Flaherty et al. N Engl J Med 2010.<br />
(5) Wang et al. Neuropathol Appl Neurobiol 2011.<br />
(6) Bos et al. Nature 2009.<br />
(7) Babic et al. Bioconjug Chem 2008.</div>St03724https://wiki.app.uib.no/mriwiki/index.php?title=Terje_Sundstr%C3%B8m_PhD_project&diff=308Terje Sundstrøm PhD project2011-08-28T20:33:58Z<p>St03724: /* Modeling melanoma brain metastasis: Towards more targeted treatment of cancer */</p>
<hr />
<div>== '''Molecular biology of melanoma brain metastasis: Potential new therapeutic targets''' ==<br />
<br />
== Terje Sundstrøm ==<br />
<br />
Terje Sundstrøm is a MD from the University of Bergen in 2005, and a resident in neurosurgery at Haukeland University Hospital from 2007. As a medical student he started clinical research in neurosurgery. His efforts have so far generated 8 publications on different neurosurgical topics (http://www.uib.no/persons/Terje.Sundstrom). Sundstrøm has during neurosurgical training been recruited to neuro-oncology and translational cancer research. He started his PhD project in January 2011 after receiving a 3-year scholarship from the Western Norway Regional Health Authority. His project on melanoma brain metastasis is a part of the Melanoma Metastasis Project headed by Professor Frits Thorsen, Translational Cancer Research Group, Department of Biomedicine, University of Bergen (http://www.uib.no/persons/Frits.Thorsen).<br />
<br />
== Project background ==<br />
<br />
Metastases are responsible for the vast majority of cancer mortality, and brain metastases occur in 1/3 of adults suffering from cancer. Metastases to the brain are 10 times more frequent than primary brain tumors. The number of patients with brain metastases is increasing because treatments for primary cancers are continually improving, and patients are surviving with these diseases longer. The treatment of brain metastases is troublesome and inadequate due to limited effects of cytostatic medications and difficult compromises with respect to consequences of radiation and surgery on surrounding brain structures.<br />
<br />
Melanoma has the highest propensity to metastasize to the brain of all cancers. The median survival time with brain metastases is 6 months. The incidence of melanoma has increased over the last 3 decades, and the death rate continues to rise faster than the rate with most cancers. Recent results have shown that it is possible to develop genetically tailored therapy to various sub-populations of patients with metastatic melanoma ('''1-4''').<br />
<br />
Unfortunately, the mechanisms for metastatic spread of melanoma to the brain are largely unknown. This is due to the lack of relevant in vivo model systems. Patients with brain metastases are often excluded from larger clinical trials, leaving us uncertain about the effect of new therapeutic modalities. New research approaches and treatment strategies are clearly needed to improve the outcome for these patients.<br />
<br />
== Project overview ==<br />
<br />
We have developed competitive animal models to study cancer metastasis and especially to the brain. This project includes extensive use of advanced imaging technology (e.g. 7 Tesla MRI, PET and bioluminescence imaging), as well as state of the art genetic and proteomic analyses through close collaboration with national and international core facilities. Our model system has unique translational possibilities in characterizing cancer metastasis and developing new target specific treatment. Biological and therapeutical considerations have motivated us to study melanoma, but any cancer can in principle be studied.<br />
<br />
In our experimental model, cell lines from human melanoma brain metastases and cell lines from primary, cutaneous melanomas are injected into the left cardiac ventricle of immunodeficient mice. In our spontaneous model, the same cell lines are injected into the skin. We have been able to show that these cells form tumors in the mice, and that the metastatic cell populations more aggressively target the brain. Some of this work has already been published ('''5'''). Preliminary results were recently presented at the AACR in the USA, and as a consequence of this, we are now in the process of establishing a cooperation with the manufacturer of one of the most promising new drugs for metastatic melanoma (Vemurafenib/PLX4032; http://www.plexxikon.com) ('''3''').<br />
<br />
It has previously been shown that breast cancer cells prelabelled with micron-sized iron oxide particles (MPIOs) and thereafter injected intracardially into mice, can be tracked by MRI as single cells in the mouse brain ('''6'''). We are currently doing comprehensive MRI studies to elucidate the metastatic patterns and growth potentials of our cell lines by using a similar particle, called Fedex ('''7'''). This work is done in collaboration with Professor Arvid Lundervold at our department. We are able to visualize single cells labelled with Fedex in the animal brains, and through mathematical modelling we can quantify the brain cell load and follow the development of brain metastases, as well as the interesting aspects of tumor dormancy in the brain. This model system gives us a reliable tool, both quantitatively and qualitatively, to study the efficacy of new treatments.<br />
<br />
We are now working to characterize functional and structural differences in the metastatic patterns of cell lines derived from primary tumors and metastases (e.g. by 7 Tesla MRI, PET and bioluminescence imaging). This work will provides us with a groundwork for a more target specific identification and validation of genetic and epigenetic alterations responsible for melanoma disbursement and growth in the brain. Through functional assessments of candidate genes by overexpression and knockout studies, we hope to contribute to the development of more target specific and effective anti-tumor therapy. We are also in the process of investigating the significance of miRNAs in the metastatic process, by selective insertion of candidate miRNAs into the tumor cells.<br />
<br />
== Figure ==<br />
<br />
[[File:Figure_1.jpg|200px|thumb|left|'''Modeling melanoma brain metastasis in the mouse'''<br />
A. MRI T1 with contrast 6 weeks after intracardial injection showing a contrast-enhancing tumor in the right hemisphere.<br />
B. 3D brain model of the same animal as in A illustrating multiple metastases.<br />
C. Optical imaging 3 weeks after intracardial injection demonstrating both abdominal and brain tumors.<br />
D. Mathematical modeling with automatic quantification of single Fedex labeled cells in the brain based on MRI T2*/MGE sequences.]]<br />
<br />
== Movie ==<br />
<br />
[[File:3D_movie_met.mov|200px|thumb|left|'''3D movie showing multiple melanoma brain metastases in a mouse brain''']]<br />
<br />
== References ==<br />
<br />
(1) Beadling et al. Clin Cancer Res 2008.<br />
(2) Carvajal et al. JAMA 2011.<br />
(3) Chapman et al. N Engl J Med 2011.<br />
(4) Flaherty et al. N Engl J Med 2010.<br />
(5) Wang et al. Neuropathol Appl Neurobiol 2011.<br />
(6) Bos et al. Nature 2009.<br />
(7) Babic et al. Bioconjug Chem 2008.</div>St03724https://wiki.app.uib.no/mriwiki/index.php?title=Terje_Sundstr%C3%B8m_PhD_project&diff=307Terje Sundstrøm PhD project2011-08-28T20:30:23Z<p>St03724: </p>
<hr />
<div>== '''Modeling melanoma brain metastasis: Towards more targeted treatment of cancer''' ==<br />
<br />
== Terje Sundstrøm ==<br />
<br />
Terje Sundstrøm is a MD from the University of Bergen in 2005, and a resident in neurosurgery at Haukeland University Hospital from 2007. As a medical student he started clinical research in neurosurgery. His efforts have so far generated 8 publications on different neurosurgical topics (http://www.uib.no/persons/Terje.Sundstrom). Sundstrøm has during neurosurgical training been recruited to neuro-oncology and translational cancer research. He started his PhD project in January 2011 after receiving a 3-year scholarship from the Western Norway Regional Health Authority. His project on melanoma brain metastasis is a part of the Melanoma Metastasis Project headed by Professor Frits Thorsen, Translational Cancer Research Group, Department of Biomedicine, University of Bergen (http://www.uib.no/persons/Frits.Thorsen).<br />
<br />
== Project background ==<br />
<br />
Metastases are responsible for the vast majority of cancer mortality, and brain metastases occur in 1/3 of adults suffering from cancer. Metastases to the brain are 10 times more frequent than primary brain tumors. The number of patients with brain metastases is increasing because treatments for primary cancers are continually improving, and patients are surviving with these diseases longer. The treatment of brain metastases is troublesome and inadequate due to limited effects of cytostatic medications and difficult compromises with respect to consequences of radiation and surgery on surrounding brain structures.<br />
<br />
Melanoma has the highest propensity to metastasize to the brain of all cancers. The median survival time with brain metastases is 6 months. The incidence of melanoma has increased over the last 3 decades, and the death rate continues to rise faster than the rate with most cancers. Recent results have shown that it is possible to develop genetically tailored therapy to various sub-populations of patients with metastatic melanoma ('''1-4''').<br />
<br />
Unfortunately, the mechanisms for metastatic spread of melanoma to the brain are largely unknown. This is due to the lack of relevant in vivo model systems. Patients with brain metastases are often excluded from larger clinical trials, leaving us uncertain about the effect of new therapeutic modalities. New research approaches and treatment strategies are clearly needed to improve the outcome for these patients.<br />
<br />
== Project overview ==<br />
<br />
We have developed competitive animal models to study cancer metastasis and especially to the brain. This project includes extensive use of advanced imaging technology (e.g. 7 Tesla MRI, PET and bioluminescence imaging), as well as state of the art genetic and proteomic analyses through close collaboration with national and international core facilities. Our model system has unique translational possibilities in characterizing cancer metastasis and developing new target specific treatment. Biological and therapeutical considerations have motivated us to study melanoma, but any cancer can in principle be studied.<br />
<br />
In our experimental model, cell lines from human melanoma brain metastases and cell lines from primary, cutaneous melanomas are injected into the left cardiac ventricle of immunodeficient mice. In our spontaneous model, the same cell lines are injected into the skin. We have been able to show that these cells form tumors in the mice, and that the metastatic cell populations more aggressively target the brain. Some of this work has already been published ('''5'''). Preliminary results were recently presented at the AACR in the USA, and as a consequence of this, we are now in the process of establishing a cooperation with the manufacturer of one of the most promising new drugs for metastatic melanoma (Vemurafenib/PLX4032; http://www.plexxikon.com) ('''3''').<br />
<br />
It has previously been shown that breast cancer cells prelabelled with micron-sized iron oxide particles (MPIOs) and thereafter injected intracardially into mice, can be tracked by MRI as single cells in the mouse brain ('''6'''). We are currently doing comprehensive MRI studies to elucidate the metastatic patterns and growth potentials of our cell lines by using a similar particle, called Fedex ('''7'''). This work is done in collaboration with Professor Arvid Lundervold at our department. We are able to visualize single cells labelled with Fedex in the animal brains, and through mathematical modelling we can quantify the brain cell load and follow the development of brain metastases, as well as the interesting aspects of tumor dormancy in the brain. This model system gives us a reliable tool, both quantitatively and qualitatively, to study the efficacy of new treatments.<br />
<br />
We are now working to characterize functional and structural differences in the metastatic patterns of cell lines derived from primary tumors and metastases (e.g. by 7 Tesla MRI, PET and bioluminescence imaging). This work will provides us with a groundwork for a more target specific identification and validation of genetic and epigenetic alterations responsible for melanoma disbursement and growth in the brain. Through functional assessments of candidate genes by overexpression and knockout studies, we hope to contribute to the development of more target specific and effective anti-tumor therapy. We are also in the process of investigating the significance of miRNAs in the metastatic process, by selective insertion of candidate miRNAs into the tumor cells.<br />
<br />
== Figure ==<br />
<br />
[[File:Figure_1.jpg|200px|thumb|left|'''Modeling melanoma brain metastasis in the mouse'''<br />
A. MRI T1 with contrast 6 weeks after intracardial injection showing a contrast-enhancing tumor in the right hemisphere.<br />
B. 3D brain model of the same animal as in A illustrating multiple metastases.<br />
C. Optical imaging 3 weeks after intracardial injection demonstrating both abdominal and brain tumors.<br />
D. Mathematical modeling with automatic quantification of single Fedex labeled cells in the brain based on MRI T2*/MGE sequences.]]<br />
<br />
== Movie ==<br />
<br />
[[File:3D_movie_met.mov|200px|thumb|left|'''3D movie showing multiple melanoma brain metastases in a mouse brain''']]<br />
<br />
== References ==<br />
<br />
(1) Beadling et al. Clin Cancer Res 2008.<br />
(2) Carvajal et al. JAMA 2011.<br />
(3) Chapman et al. N Engl J Med 2011.<br />
(4) Flaherty et al. N Engl J Med 2010.<br />
(5) Wang et al. Neuropathol Appl Neurobiol 2011.<br />
(6) Bos et al. Nature 2009.<br />
(7) Babic et al. Bioconjug Chem 2008.</div>St03724https://wiki.app.uib.no/mriwiki/index.php?title=File:3D_movie_met.mov&diff=306File:3D movie met.mov2011-08-28T20:27:05Z<p>St03724: 3D movie of multiple brain metastases in a mouse</p>
<hr />
<div>3D movie of multiple brain metastases in a mouse</div>St03724https://wiki.app.uib.no/mriwiki/index.php?title=Terje_Sundstr%C3%B8m_PhD_project&diff=305Terje Sundstrøm PhD project2011-08-28T20:01:49Z<p>St03724: </p>
<hr />
<div>== '''Modeling melanoma brain metastasis: Towards more targeted treatment of cancer''' ==<br />
<br />
== Terje Sundstrøm ==<br />
<br />
Terje Sundstrøm is a MD from the University of Bergen in 2005, and a resident in neurosurgery at Haukeland University Hospital from 2007. As a medical student he started clinical research in neurosurgery. His efforts have so far generated 8 publications on different neurosurgical topics (http://www.uib.no/persons/Terje.Sundstrom). Sundstrøm has during neurosurgical training been recruited to neuro-oncology and translational cancer research. He started his PhD project in January 2011 after receiving a 3-year scholarship from the Western Norway Regional Health Authority. His project on melanoma brain metastasis is a part of the Melanoma Metastasis Project headed by Professor Frits Thorsen, Translational Cancer Research Group, Department of Biomedicine, University of Bergen (http://www.uib.no/persons/Frits.Thorsen).<br />
<br />
== Project background ==<br />
<br />
Metastases are responsible for the vast majority of cancer mortality, and brain metastases occur in 1/3 of adults suffering from cancer. Metastases to the brain are 10 times more frequent than primary brain tumors. The number of patients with brain metastases is increasing because treatments for primary cancers are continually improving, and patients are surviving with these diseases longer. The treatment of brain metastases is troublesome and inadequate due to limited effects of cytostatic medications and difficult compromises with respect to consequences of radiation and surgery on surrounding brain structures.<br />
<br />
Melanoma has the highest propensity to metastasize to the brain of all cancers. The median survival time with brain metastases is 6 months. The incidence of melanoma has increased over the last 3 decades, and the death rate continues to rise faster than the rate with most cancers. Recent results have shown that it is possible to develop genetically tailored therapy to various sub-populations of patients with metastatic melanoma ('''1-4''').<br />
<br />
Unfortunately, the mechanisms for metastatic spread of melanoma to the brain are largely unknown. This is due to the lack of relevant in vivo model systems. Patients with brain metastases are often excluded from larger clinical trials, leaving us uncertain about the effect of new therapeutic modalities. New research approaches and treatment strategies are clearly needed to improve the outcome for these patients.<br />
<br />
== Project overview ==<br />
<br />
We have developed competitive animal models to study cancer metastasis and especially to the brain. This project includes extensive use of advanced imaging technology (e.g. 7 Tesla MRI, PET and bioluminescence imaging), as well as state of the art genetic and proteomic analyses through close collaboration with national and international core facilities. Our model system has unique translational possibilities in characterizing cancer metastasis and developing new target specific treatment. Biological and therapeutical considerations have motivated us to study melanoma, but any cancer can in principle be studied.<br />
<br />
In our experimental model, cell lines from human melanoma brain metastases and cell lines from primary, cutaneous melanomas are injected into the left cardiac ventricle of immunodeficient mice. In our spontaneous model, the same cell lines are injected into the skin. We have been able to show that these cells form tumors in the mice, and that the metastatic cell populations more aggressively target the brain. Some of this work has already been published ('''5'''). Preliminary results were recently presented at the AACR in the USA, and as a consequence of this, we are now in the process of establishing a cooperation with the manufacturer of one of the most promising new drugs for metastatic melanoma (Vemurafenib/PLX4032; http://www.plexxikon.com) ('''3''').<br />
<br />
It has previously been shown that breast cancer cells prelabelled with micron-sized iron oxide particles (MPIOs) and thereafter injected intracardially into mice, can be tracked by MRI as single cells in the mouse brain ('''6'''). We are currently doing comprehensive MRI studies to elucidate the metastatic patterns and growth potentials of our cell lines by using a similar particle, called Fedex ('''7'''). This work is done in collaboration with Professor Arvid Lundervold at our department. We are able to visualize single cells labelled with Fedex in the animal brains, and through mathematical modelling we can quantify the brain cell load and follow the development of brain metastases, as well as the interesting aspects of tumor dormancy in the brain. This model system gives us a reliable tool, both quantitatively and qualitatively, to study the efficacy of new treatments.<br />
<br />
We are now working to characterize functional and structural differences in the metastatic patterns of cell lines derived from primary tumors and metastases (e.g. by 7 Tesla MRI, PET and bioluminescence imaging). This work will provides us with a groundwork for a more target specific identification and validation of genetic and epigenetic alterations responsible for melanoma disbursement and growth in the brain. Through functional assessments of candidate genes by overexpression and knockout studies, we hope to contribute to the development of more target specific and effective anti-tumor therapy. We are also in the process of investigating the significance of miRNAs in the metastatic process, by selective insertion of candidate miRNAs into the tumor cells.<br />
<br />
== Figure ==<br />
<br />
[[File:Figure_1.jpg|200px|thumb|left|'''Modeling melanoma brain metastasis in the mouse'''<br />
A. MRI T1 with contrast 6 weeks after intracardial injection showing a contrast-enhancing tumor in the right hemisphere.<br />
B. 3D brain model of the same animal as in A illustrating multiple metastases.<br />
C. Optical imaging 3 weeks after intracardial injection demonstrating both abdominal and brain tumors.<br />
D. Mathematical modeling with automatic quantification of single Fedex labeled cells in the brain based on MRI T2*/MGE sequences.]]<br />
<br />
== Movie ==<br />
<br />
[[File:3D_movie_web.mov|200px|thumb|left|alt text]]<br />
<br />
'''3D movie showing multiple melanoma brain metastases in a mouse brain'''<br />
<br />
== References ==<br />
<br />
(1) Beadling et al. Clin Cancer Res 2008.<br />
(2) Carvajal et al. JAMA 2011.<br />
(3) Chapman et al. N Engl J Med 2011.<br />
(4) Flaherty et al. N Engl J Med 2010.<br />
(5) Wang et al. Neuropathol Appl Neurobiol 2011.<br />
(6) Bos et al. Nature 2009.<br />
(7) Babic et al. Bioconjug Chem 2008.</div>St03724https://wiki.app.uib.no/mriwiki/index.php?title=Terje_Sundstr%C3%B8m_PhD_project&diff=304Terje Sundstrøm PhD project2011-08-28T19:56:05Z<p>St03724: </p>
<hr />
<div>== '''Modeling melanoma brain metastasis: Towards more targeted treatment of cancer''' ==<br />
<br />
== Terje Sundstrøm ==<br />
<br />
Terje Sundstrøm is a MD from the University of Bergen in 2005, and a resident in neurosurgery at Haukeland University Hospital from 2007. As a medical student he started clinical research in neurosurgery. His efforts have so far generated 8 publications on different neurosurgical topics (http://www.uib.no/persons/Terje.Sundstrom). Sundstrøm has during neurosurgical training been recruited to neuro-oncology and translational cancer research. He started his PhD project in January 2011 after receiving a 3-year scholarship from the Western Norway Regional Health Authority. His project on melanoma brain metastasis is a part of the Melanoma Metastasis Project headed by Professor Frits Thorsen, Translational Cancer Research Group, Department of Biomedicine, University of Bergen (http://www.uib.no/persons/Frits.Thorsen).<br />
<br />
== Project background ==<br />
<br />
Metastases are responsible for the vast majority of cancer mortality, and brain metastases occur in 1/3 of adults suffering from cancer. Metastases to the brain are 10 times more frequent than primary brain tumors. The number of patients with brain metastases is increasing because treatments for primary cancers are continually improving, and patients are surviving with these diseases longer. The treatment of brain metastases is troublesome and inadequate due to limited effects of cytostatic medications and difficult compromises with respect to consequences of radiation and surgery on surrounding brain structures.<br />
<br />
Melanoma has the highest propensity to metastasize to the brain of all cancers. The median survival time with brain metastases is 6 months. The incidence of melanoma has increased over the last 3 decades, and the death rate continues to rise faster than the rate with most cancers. Recent results have shown that it is possible to develop genetically tailored therapy to various sub-populations of patients with metastatic melanoma ('''1-4''').<br />
<br />
Unfortunately, the mechanisms for metastatic spread of melanoma to the brain are largely unknown. This is due to the lack of relevant in vivo model systems. Patients with brain metastases are often excluded from larger clinical trials, leaving us uncertain about the effect of new therapeutic modalities. New research approaches and treatment strategies are clearly needed to improve the outcome for these patients.<br />
<br />
== Project overview ==<br />
<br />
We have developed competitive animal models to study cancer metastasis and especially to the brain. This project includes extensive use of advanced imaging technology (e.g. 7 Tesla MRI, PET and bioluminescence imaging), as well as state of the art genetic and proteomic analyses through close collaboration with national and international core facilities. Our model system has unique translational possibilities in characterizing cancer metastasis and developing new target specific treatment. Biological and therapeutical considerations have motivated us to study melanoma, but any cancer can in principle be studied.<br />
<br />
In our experimental model, cell lines from human melanoma brain metastases and cell lines from primary, cutaneous melanomas are injected into the left cardiac ventricle of immunodeficient mice. In our spontaneous model, the same cell lines are injected into the skin. We have been able to show that these cells form tumors in the mice, and that the metastatic cell populations more aggressively target the brain. Some of this work has already been published ('''5'''). Preliminary results were recently presented at the AACR in the USA, and as a consequence of this, we are now in the process of establishing a cooperation with the manufacturer of one of the most promising new drugs for metastatic melanoma (Vemurafenib/PLX4032; http://www.plexxikon.com) ('''3''').<br />
<br />
It has previously been shown that breast cancer cells prelabelled with micron-sized iron oxide particles (MPIOs) and thereafter injected intracardially into mice, can be tracked by MRI as single cells in the mouse brain ('''6'''). We are currently doing comprehensive MRI studies to elucidate the metastatic patterns and growth potentials of our cell lines by using a similar particle, called Fedex ('''7'''). This work is done in collaboration with Professor Arvid Lundervold at our department. We are able to visualize single cells labelled with Fedex in the animal brains, and through mathematical modelling we can quantify the brain cell load and follow the development of brain metastases, as well as the interesting aspects of tumor dormancy in the brain. This model system gives us a reliable tool, both quantitatively and qualitatively, to study the efficacy of new treatments.<br />
<br />
We are now working to characterize functional and structural differences in the metastatic patterns of cell lines derived from primary tumors and metastases (e.g. by 7 Tesla MRI, PET and bioluminescence imaging). This work will provides us with a groundwork for a more target specific identification and validation of genetic and epigenetic alterations responsible for melanoma disbursement and growth in the brain. Through functional assessments of candidate genes by overexpression and knockout studies, we hope to contribute to the development of more target specific and effective anti-tumor therapy. We are also in the process of investigating the significance of miRNAs in the metastatic process, by selective insertion of candidate miRNAs into the tumor cells.<br />
<br />
== Figure ==<br />
<br />
[[File:Figure_1.jpg|200px|thumb|left|alt text]]<br />
<br />
'''Modeling melanoma brain metastasis in the mouse'''<br />
A. MRI T1 with contrast 6 weeks after intracardial injection showing a contrast-enhancing tumor in the right hemisphere.<br />
B. 3D brain model of the same animal as in A illustrating multiple metastases.<br />
C. Optical imaging 3 weeks after intracardial injection demonstrating both abdominal and brain tumors.<br />
D. Mathematical modeling with automatic quantification of single Fedex labeled cells in the brain based on MRI T2*/MGE sequences.<br />
<br />
== Movie ==<br />
<br />
[[File:3D_movie_web.mov|200px|thumb|left|alt text]]<br />
<br />
'''3D movie showing multiple melanoma brain metastases in a mouse brain'''<br />
<br />
== References ==<br />
<br />
(1) Beadling et al. Clin Cancer Res 2008.<br />
(2) Carvajal et al. JAMA 2011.<br />
(3) Chapman et al. N Engl J Med 2011.<br />
(4) Flaherty et al. N Engl J Med 2010.<br />
(5) Wang et al. Neuropathol Appl Neurobiol 2011.<br />
(6) Bos et al. Nature 2009.<br />
(7) Babic et al. Bioconjug Chem 2008.</div>St03724https://wiki.app.uib.no/mriwiki/index.php?title=Terje_Sundstr%C3%B8m_PhD_project&diff=303Terje Sundstrøm PhD project2011-08-28T19:49:19Z<p>St03724: </p>
<hr />
<div>== '''Modeling melanoma brain metastasis: Towards more targeted treatment of cancer''' ==<br />
<br />
== Terje Sundstrøm ==<br />
<br />
Terje Sundstrøm is a MD from the University of Bergen in 2005, and a resident in neurosurgery at Haukeland University Hospital from 2007. As a medical student he started clinical research in neurosurgery. His efforts have so far generated 8 publications on different neurosurgical topics (http://www.uib.no/persons/Terje.Sundstrom). Sundstrøm has during neurosurgical training been recruited to neuro-oncology and translational cancer research. He started his PhD project in January 2011 after receiving a 3-year scholarship from the Western Norway Regional Health Authority. His project on melanoma brain metastasis is a part of the Melanoma Metastasis Project headed by Professor Frits Thorsen, Translational Cancer Research Group, Department of Biomedicine, University of Bergen (http://www.uib.no/persons/Frits.Thorsen).<br />
<br />
== Project background ==<br />
<br />
Metastases are responsible for the vast majority of cancer mortality, and brain metastases occur in 1/3 of adults suffering from cancer. Metastases to the brain are 10 times more frequent than primary brain tumors. The number of patients with brain metastases is increasing because treatments for primary cancers are continually improving, and patients are surviving with these diseases longer. The treatment of brain metastases is troublesome and inadequate due to limited effects of cytostatic medications and difficult compromises with respect to consequences of radiation and surgery on surrounding brain structures.<br />
<br />
Melanoma has the highest propensity to metastasize to the brain of all cancers. The median survival time with brain metastases is 6 months. The incidence of melanoma has increased over the last 3 decades, and the death rate continues to rise faster than the rate with most cancers. Recent results have shown that it is possible to develop genetically tailored therapy to various sub-populations of patients with metastatic melanoma ('''1-4''').<br />
<br />
Unfortunately, the mechanisms for metastatic spread of melanoma to the brain are largely unknown. This is due to the lack of relevant in vivo model systems. Patients with brain metastases are often excluded from larger clinical trials, leaving us uncertain about the effect of new therapeutic modalities. New research approaches and treatment strategies are clearly needed to improve the outcome for these patients.<br />
<br />
== Project overview ==<br />
<br />
We have developed competitive animal models to study cancer metastasis and especially to the brain. This project includes extensive use of advanced imaging technology (e.g. 7 Tesla MRI, PET and bioluminescence imaging), as well as state of the art genetic and proteomic analyses through close collaboration with national and international core facilities. Our model system has unique translational possibilities in characterizing cancer metastasis and developing new target specific treatment. Biological and therapeutical considerations have motivated us to study melanoma, but any cancer can in principle be studied.<br />
<br />
In our experimental model, cell lines from human melanoma brain metastases and cell lines from primary, cutaneous melanomas are injected into the left cardiac ventricle of immunodeficient mice. In our spontaneous model, the same cell lines are injected into the skin. We have been able to show that these cells form tumors in the mice, and that the metastatic cell populations more aggressively target the brain. Some of this work has already been published ('''5'''). Preliminary results were recently presented at the AACR in the USA, and as a consequence of this, we are now in the process of establishing a cooperation with the manufacturer of one of the most promising new drugs for metastatic melanoma (Vemurafenib/PLX4032; http://www.plexxikon.com) ('''3''').<br />
<br />
It has previously been shown that breast cancer cells prelabelled with micron-sized iron oxide particles (MPIOs) and thereafter injected intracardially into mice, can be tracked by MRI as single cells in the mouse brain ('''6'''). We are currently doing comprehensive MRI studies to elucidate the metastatic patterns and growth potentials of our cell lines by using a similar particle, called Fedex ('''7'''). This work is done in collaboration with Professor Arvid Lundervold at our department. We are able to visualize single cells labelled with Fedex in the animal brains, and through mathematical modelling we can quantify the brain cell load and follow the development of brain metastases, as well as the interesting aspects of tumor dormancy in the brain. This model system gives us a reliable tool, both quantitatively and qualitatively, to study the efficacy of new treatments.<br />
<br />
We are now working to characterize functional and structural differences in the metastatic patterns of cell lines derived from primary tumors and metastases (e.g. by 7 Tesla MRI, PET and bioluminescence imaging). This work will provides us with a groundwork for a more target specific identification and validation of genetic and epigenetic alterations responsible for melanoma disbursement and growth in the brain. Through functional assessments of candidate genes by overexpression and knockout studies, we hope to contribute to the development of more target specific and effective anti-tumor therapy. We are also in the process of investigating the significance of miRNAs in the metastatic process, by selective insertion of candidate miRNAs into the tumor cells.<br />
<br />
== Figure 1 ==<br />
<br />
[[File:Figure_1.jpg|200px|thumb|left|alt text]]<br />
<br />
'''Figure 1 Modeling melanoma brain metastasis in the mouse'''<br />
A. MRI T1 with contrast 6 weeks after intracardial injection showing a contrast-enhancing tumor in the right hemisphere.<br />
B. 3D brain model of the same animal as in A illustrating multiple metastases.<br />
C. Optical imaging 3 weeks after intracardial injection demonstrating both abdominal and brain tumors.<br />
D. Mathematical modeling with automatic quantification of single Fedex labeled cells in the brain based on MRI T2*/MGE sequences.<br />
<br />
== Figure 2 ==<br />
<br />
[[File:[[File:3D_movie_web.mov|200px|thumb|left|alt text]]]]<br />
<br />
'''Figure 2 3D movie showing multiple melanoma brain metastases in a mouse brain'''<br />
<br />
== References ==<br />
<br />
(1) Beadling et al. Clin Cancer Res 2008.<br />
(2) Carvajal et al. JAMA 2011.<br />
(3) Chapman et al. N Engl J Med 2011.<br />
(4) Flaherty et al. N Engl J Med 2010.<br />
(5) Wang et al. Neuropathol Appl Neurobiol 2011.<br />
(6) Bos et al. Nature 2009.<br />
(7) Babic et al. Bioconjug Chem 2008.</div>St03724https://wiki.app.uib.no/mriwiki/index.php?title=Terje_Sundstr%C3%B8m_PhD_project&diff=302Terje Sundstrøm PhD project2011-08-28T19:47:38Z<p>St03724: </p>
<hr />
<div>== '''Modeling melanoma brain metastasis: Towards more targeted treatment of cancer''' ==<br />
<br />
== Terje Sundstrøm ==<br />
<br />
Terje Sundstrøm is a MD from the University of Bergen in 2005, and a resident in neurosurgery at Haukeland University Hospital from 2007. As a medical student he started clinical research in neurosurgery. His efforts have so far generated 8 publications on different neurosurgical topics (http://www.uib.no/persons/Terje.Sundstrom). Sundstrøm has during neurosurgical training been recruited to neuro-oncology and translational cancer research. He started his PhD project in January 2011 after receiving a 3-year scholarship from the Western Norway Regional Health Authority. His project on melanoma brain metastasis is a part of the Melanoma Metastasis Project headed by Professor Frits Thorsen, Translational Cancer Research Group, Department of Biomedicine, University of Bergen (http://www.uib.no/persons/Frits.Thorsen).<br />
<br />
== Project background ==<br />
<br />
Metastases are responsible for the vast majority of cancer mortality, and brain metastases occur in 1/3 of adults suffering from cancer. Metastases to the brain are 10 times more frequent than primary brain tumors. The number of patients with brain metastases is increasing because treatments for primary cancers are continually improving, and patients are surviving with these diseases longer. The treatment of brain metastases is troublesome and inadequate due to limited effects of cytostatic medications and difficult compromises with respect to consequences of radiation and surgery on surrounding brain structures.<br />
<br />
Melanoma has the highest propensity to metastasize to the brain of all cancers. The median survival time with brain metastases is 6 months. The incidence of melanoma has increased over the last 3 decades, and the death rate continues to rise faster than the rate with most cancers. Recent results have shown that it is possible to develop genetically tailored therapy to various sub-populations of patients with metastatic melanoma ('''1-4''').<br />
<br />
Unfortunately, the mechanisms for metastatic spread of melanoma to the brain are largely unknown. This is due to the lack of relevant in vivo model systems. Patients with brain metastases are often excluded from larger clinical trials, leaving us uncertain about the effect of new therapeutic modalities. New research approaches and treatment strategies are clearly needed to improve the outcome for these patients.<br />
<br />
== Project overview ==<br />
<br />
We have developed competitive animal models to study cancer metastasis and especially to the brain. This project includes extensive use of advanced imaging technology (e.g. 7 Tesla MRI, PET and bioluminescence imaging), as well as state of the art genetic and proteomic analyses through close collaboration with national and international core facilities. Our model system has unique translational possibilities in characterizing cancer metastasis and developing new target specific treatment. Biological and therapeutical considerations have motivated us to study melanoma, but any cancer can in principle be studied.<br />
<br />
In our experimental model, cell lines from human melanoma brain metastases and cell lines from primary, cutaneous melanomas are injected into the left cardiac ventricle of immunodeficient mice. In our spontaneous model, the same cell lines are injected into the skin. We have been able to show that these cells form tumors in the mice, and that the metastatic cell populations more aggressively target the brain. Some of this work has already been published ('''5'''). Preliminary results were recently presented at the AACR in the USA, and as a consequence of this, we are now in the process of establishing a cooperation with the manufacturer of one of the most promising new drugs for metastatic melanoma (Vemurafenib/PLX4032; http://www.plexxikon.com) ('''3''').<br />
<br />
It has previously been shown that breast cancer cells prelabelled with micron-sized iron oxide particles (MPIOs) and thereafter injected intracardially into mice, can be tracked by MRI as single cells in the mouse brain ('''6'''). We are currently doing comprehensive MRI studies to elucidate the metastatic patterns and growth potentials of our cell lines by using a similar particle, called Fedex ('''7'''). This work is done in collaboration with Professor Arvid Lundervold at our department. We are able to visualize single cells labelled with Fedex in the animal brains, and through mathematical modelling we can quantify the brain cell load and follow the development of brain metastases, as well as the interesting aspects of tumor dormancy in the brain. This model system gives us a reliable tool, both quantitatively and qualitatively, to study the efficacy of new treatments.<br />
<br />
We are now working to characterize functional and structural differences in the metastatic patterns of cell lines derived from primary tumors and metastases (e.g. by 7 Tesla MRI, PET and bioluminescence imaging). This work will provides us with a groundwork for a more target specific identification and validation of genetic and epigenetic alterations responsible for melanoma disbursement and growth in the brain. Through functional assessments of candidate genes by overexpression and knockout studies, we hope to contribute to the development of more target specific and effective anti-tumor therapy. We are also in the process of investigating the significance of miRNAs in the metastatic process, by selective insertion of candidate miRNAs into the tumor cells.<br />
<br />
== Figure 1 ==<br />
<br />
[[File:Figure_1.jpg|200px|thumb|left|alt text]]<br />
<br />
'''Figure 1 Modeling melanoma brain metastasis in the mouse'''<br />
A. MRI T1 with contrast 6 weeks after intracardial injection showing a contrast-enhancing tumor in the right hemisphere.<br />
B. 3D brain model of the same animal as in A illustrating multiple metastases.<br />
C. Optical imaging 3 weeks after intracardial injection demonstrating both abdominal and brain tumors.<br />
D. Mathematical modeling with automatic quantification of single Fedex labeled cells in the brain based on MRI T2*/MGE sequences.<br />
<br />
== Figure 2 ==<br />
<br />
[[File:3D_movie_web.mov|200px|thumb|left|alt text]]<br />
<br />
'''Figure 2 3D movie showing multiple melanoma brain metastases in a mouse brain'''<br />
<br />
== References ==<br />
<br />
(1) Beadling et al. Clin Cancer Res 2008.<br />
(2) Carvajal et al. JAMA 2011.<br />
(3) Chapman et al. N Engl J Med 2011.<br />
(4) Flaherty et al. N Engl J Med 2010.<br />
(5) Wang et al. Neuropathol Appl Neurobiol 2011.<br />
(6) Bos et al. Nature 2009.<br />
(7) Babic et al. Bioconjug Chem 2008.</div>St03724https://wiki.app.uib.no/mriwiki/index.php?title=File:3D_movie_web.mov&diff=301File:3D movie web.mov2011-08-28T19:44:55Z<p>St03724: 3D Movie Brain Metastases</p>
<hr />
<div>3D Movie Brain Metastases</div>St03724https://wiki.app.uib.no/mriwiki/index.php?title=Terje_Sundstr%C3%B8m_PhD_project&diff=300Terje Sundstrøm PhD project2011-08-28T19:39:49Z<p>St03724: </p>
<hr />
<div>== '''Modeling melanoma brain metastasis: Towards more targeted treatment of cancer''' ==<br />
<br />
== Terje Sundstrøm ==<br />
<br />
Terje Sundstrøm is a MD from the University of Bergen in 2005, and a resident in neurosurgery at Haukeland University Hospital from 2007. As a medical student he started clinical research in neurosurgery. His efforts have so far generated 8 publications on different neurosurgical topics (http://www.uib.no/persons/Terje.Sundstrom). Sundstrøm has during neurosurgical training been recruited to neuro-oncology and translational cancer research. He started his PhD project in January 2011 after receiving a 3-year scholarship from the Western Norway Regional Health Authority. His project on melanoma brain metastasis is a part of the Melanoma Metastasis Project headed by Professor Frits Thorsen, Translational Cancer Research Group, Department of Biomedicine, University of Bergen (http://www.uib.no/persons/Frits.Thorsen).<br />
<br />
== Project background ==<br />
<br />
Metastases are responsible for the vast majority of cancer mortality, and brain metastases occur in 1/3 of adults suffering from cancer. Metastases to the brain are 10 times more frequent than primary brain tumors. The number of patients with brain metastases is increasing because treatments for primary cancers are continually improving, and patients are surviving with these diseases longer. The treatment of brain metastases is troublesome and inadequate due to limited effects of cytostatic medications and difficult compromises with respect to consequences of radiation and surgery on surrounding brain structures.<br />
<br />
Melanoma has the highest propensity to metastasize to the brain of all cancers. The median survival time with brain metastases is 6 months. The incidence of melanoma has increased over the last 3 decades, and the death rate continues to rise faster than the rate with most cancers. Recent results have shown that it is possible to develop genetically tailored therapy to various sub-populations of patients with metastatic melanoma ('''1-4''').<br />
<br />
Unfortunately, the mechanisms for metastatic spread of melanoma to the brain are largely unknown. This is due to the lack of relevant in vivo model systems. Patients with brain metastases are often excluded from larger clinical trials, leaving us uncertain about the effect of new therapeutic modalities. New research approaches and treatment strategies are clearly needed to improve the outcome for these patients.<br />
<br />
== Project overview ==<br />
<br />
We have developed competitive animal models to study cancer metastasis and especially to the brain. This project includes extensive use of advanced imaging technology (e.g. 7 Tesla MRI, PET and bioluminescence imaging), as well as state of the art genetic and proteomic analyses through close collaboration with national and international core facilities. Our model system has unique translational possibilities in characterizing cancer metastasis and developing new target specific treatment. Biological and therapeutical considerations have motivated us to study melanoma, but any cancer can in principle be studied.<br />
<br />
In our experimental model, cell lines from human melanoma brain metastases and cell lines from primary, cutaneous melanomas are injected into the left cardiac ventricle of immunodeficient mice. In our spontaneous model, the same cell lines are injected into the skin. We have been able to show that these cells form tumors in the mice, and that the metastatic cell populations more aggressively target the brain. Some of this work has already been published ('''5'''). Preliminary results were recently presented at the AACR in the USA, and as a consequence of this, we are now in the process of establishing a cooperation with the manufacturer of one of the most promising new drugs for metastatic melanoma (Vemurafenib/PLX4032; http://www.plexxikon.com) ('''3''').<br />
<br />
It has previously been shown that breast cancer cells prelabelled with micron-sized iron oxide particles (MPIOs) and thereafter injected intracardially into mice, can be tracked by MRI as single cells in the mouse brain ('''6'''). We are currently doing comprehensive MRI studies to elucidate the metastatic patterns and growth potentials of our cell lines by using a similar particle, called Fedex ('''7'''). This work is done in collaboration with Professor Arvid Lundervold at our department. We are able to visualize single cells labelled with Fedex in the animal brains, and through mathematical modelling we can quantify the brain cell load and follow the development of brain metastases, as well as the interesting aspects of tumor dormancy in the brain. This model system gives us a reliable tool, both quantitatively and qualitatively, to study the efficacy of new treatments.<br />
<br />
We are now working to characterize functional and structural differences in the metastatic patterns of cell lines derived from primary tumors and metastases (e.g. by 7 Tesla MRI, PET and bioluminescence imaging). This work will provides us with a groundwork for a more target specific identification and validation of genetic and epigenetic alterations responsible for melanoma disbursement and growth in the brain. Through functional assessments of candidate genes by overexpression and knockout studies, we hope to contribute to the development of more target specific and effective anti-tumor therapy. We are also in the process of investigating the significance of miRNAs in the metastatic process, by selective insertion of candidate miRNAs into the tumor cells.<br />
<br />
== Figure 1 ==<br />
<br />
[[File:Figure_1.jpg|200px|thumb|left|alt text]]<br />
<br />
'''Figure 1 Modeling melanoma brain metastasis in the mouse'''<br />
A. MRI T1 with contrast 6 weeks after intracardial injection showing a contrast-enhancing tumor in the right hemisphere.<br />
B. 3D brain model of the same animal as in A illustrating multiple metastases.<br />
C. Optical imaging 3 weeks after intracardial injection demonstrating both abdominal and brain tumors.<br />
D. Mathematical modeling with automatic quantification of single Fedex labeled cells in the brain based on MRI T2*/MGE sequences.<br />
<br />
== References ==<br />
<br />
(1) Beadling et al. Clin Cancer Res 2008.<br />
(2) Carvajal et al. JAMA 2011.<br />
(3) Chapman et al. N Engl J Med 2011.<br />
(4) Flaherty et al. N Engl J Med 2010.<br />
(5) Wang et al. Neuropathol Appl Neurobiol 2011.<br />
(6) Bos et al. Nature 2009.<br />
(7) Babic et al. Bioconjug Chem 2008.</div>St03724https://wiki.app.uib.no/mriwiki/index.php?title=Terje_Sundstr%C3%B8m_PhD_project&diff=299Terje Sundstrøm PhD project2011-08-28T19:38:24Z<p>St03724: </p>
<hr />
<div>== '''Modeling melanoma brain metastasis: Towards more targeted treatment of cancer''' ==<br />
<br />
== Terje Sundstrøm ==<br />
<br />
Terje Sundstrøm is a MD from the University of Bergen in 2005, and a resident in neurosurgery at Haukeland University Hospital from 2007. As a medical student he started clinical research in neurosurgery. His efforts have so far generated 8 publications on different neurosurgical topics (http://www.uib.no/persons/Terje.Sundstrom). Sundstrøm has during neurosurgical training been recruited to neuro-oncology and translational cancer research. He started his PhD project in January 2011 after receiving a 3-year scholarship from the Western Norway Regional Health Authority. His project on melanoma brain metastasis is a part of the Melanoma Metastasis Project headed by Professor Frits Thorsen, Translational Cancer Research Group, Department of Biomedicine, University of Bergen (http://www.uib.no/persons/Frits.Thorsen).<br />
<br />
== Project background ==<br />
<br />
Metastases are responsible for the vast majority of cancer mortality, and brain metastases occur in 1/3 of adults suffering from cancer. Metastases to the brain are 10 times more frequent than primary brain tumors. The number of patients with brain metastases is increasing because treatments for primary cancers are continually improving, and patients are surviving with these diseases longer. The treatment of brain metastases is troublesome and inadequate due to limited effects of cytostatic medications and difficult compromises with respect to consequences of radiation and surgery on surrounding brain structures.<br />
<br />
Melanoma has the highest propensity to metastasize to the brain of all cancers. The median survival time with brain metastases is 6 months. The incidence of melanoma has increased over the last 3 decades, and the death rate continues to rise faster than the rate with most cancers. Recent results have shown that it is possible to develop genetically tailored therapy to various sub-populations of patients with metastatic melanoma ('''1-4''').<br />
<br />
Unfortunately, the mechanisms for metastatic spread of melanoma to the brain are largely unknown. This is due to the lack of relevant in vivo model systems. Patients with brain metastases are often excluded from larger clinical trials, leaving us uncertain about the effect of new therapeutic modalities. New research approaches and treatment strategies are clearly needed to improve the outcome for these patients.<br />
<br />
== Project overview ==<br />
<br />
We have developed competitive animal models to study cancer metastasis and especially to the brain. This project includes extensive use of advanced imaging technology (e.g. 7 Tesla MRI, PET and bioluminescence imaging), as well as state of the art genetic and proteomic analyses through close collaboration with national and international core facilities. Our model system has unique translational possibilities in characterizing cancer metastasis and developing new target specific treatment. Biological and therapeutical considerations have motivated us to study melanoma, but any cancer can in principle be studied.<br />
<br />
In our experimental model, cell lines from human melanoma brain metastases and cell lines from primary, cutaneous melanomas are injected into the left cardiac ventricle of immunodeficient mice. In our spontaneous model, the same cell lines are injected into the skin. We have been able to show that these cells form tumors in the mice, and that the metastatic cell populations more aggressively target the brain. Some of this work has already been published ('''5'''). Preliminary results were recently presented at the AACR in the USA, and as a consequence of this, we are now in the process of establishing a cooperation with the manufacturer of one of the most promising new drugs for metastatic melanoma (Vemurafenib/PLX4032; http://www.plexxikon.com) ('''3''').<br />
<br />
[[File:Figure_1.jpg|200px|thumb|left|alt text]]<br />
<br />
'''Figure Modeling melanoma brain metastasis in the mouse'''<br />
A. MRI T1 with contrast 6 weeks after intracardial injection showing a contrast-enhancing tumor in the right hemisphere.<br />
B. 3D brain model of the same animal as in A illustrating multiple metastases.<br />
C. Optical imaging 3 weeks after intracardial injection demonstrating both abdominal and brain tumors.<br />
D. Mathematical modeling with automatic quantification of single Fedex labeled cells in the brain based on MRI T2*/MGE sequences.<br />
<br />
It has previously been shown that breast cancer cells prelabelled with micron-sized iron oxide particles (MPIOs) and thereafter injected intracardially into mice, can be tracked by MRI as single cells in the mouse brain ('''6'''). We are currently doing comprehensive MRI studies to elucidate the metastatic patterns and growth potentials of our cell lines by using a similar particle, called Fedex ('''7'''). This work is done in collaboration with Professor Arvid Lundervold at our department. We are able to visualize single cells labelled with Fedex in the animal brains, and through mathematical modelling we can quantify the brain cell load and follow the development of brain metastases, as well as the interesting aspects of tumor dormancy in the brain. This model system gives us a reliable tool, both quantitatively and qualitatively, to study the efficacy of new treatments.<br />
<br />
We are now working to characterize functional and structural differences in the metastatic patterns of cell lines derived from primary tumors and metastases (e.g. by 7 Tesla MRI, PET and bioluminescence imaging). This work will provides us with a groundwork for a more target specific identification and validation of genetic and epigenetic alterations responsible for melanoma disbursement and growth in the brain. Through functional assessments of candidate genes by overexpression and knockout studies, we hope to contribute to the development of more target specific and effective anti-tumor therapy. We are also in the process of investigating the significance of miRNAs in the metastatic process, by selective insertion of candidate miRNAs into the tumor cells.<br />
<br />
== References ==<br />
<br />
(1) Beadling et al. Clin Cancer Res 2008.<br />
(2) Carvajal et al. JAMA 2011.<br />
(3) Chapman et al. N Engl J Med 2011.<br />
(4) Flaherty et al. N Engl J Med 2010.<br />
(5) Wang et al. Neuropathol Appl Neurobiol 2011.<br />
(6) Bos et al. Nature 2009.<br />
(7) Babic et al. Bioconjug Chem 2008.</div>St03724https://wiki.app.uib.no/mriwiki/index.php?title=Terje_Sundstr%C3%B8m_PhD_project&diff=298Terje Sundstrøm PhD project2011-08-28T19:36:47Z<p>St03724: </p>
<hr />
<div>== '''Modeling melanoma brain metastasis: Towards more targeted treatment of cancer''' ==<br />
<br />
== Terje Sundstrøm ==<br />
<br />
Terje Sundstrøm is a MD from the University of Bergen in 2005, and a resident in neurosurgery at Haukeland University Hospital from 2007. As a medical student he started clinical research in neurosurgery. His efforts have so far generated 8 publications on different neurosurgical topics (http://www.uib.no/persons/Terje.Sundstrom). Sundstrøm has during neurosurgical training been recruited to neuro-oncology and translational cancer research. He started his PhD project in January 2011 after receiving a 3-year scholarship from the Western Norway Regional Health Authority. His project on melanoma brain metastasis is a part of the Melanoma Metastasis Project headed by Professor Frits Thorsen, Translational Cancer Research Group, Department of Biomedicine, University of Bergen (http://www.uib.no/persons/Frits.Thorsen).<br />
<br />
== Project background ==<br />
<br />
Metastases are responsible for the vast majority of cancer mortality, and brain metastases occur in 1/3 of adults suffering from cancer. Metastases to the brain are 10 times more frequent than primary brain tumors. The number of patients with brain metastases is increasing because treatments for primary cancers are continually improving, and patients are surviving with these diseases longer. The treatment of brain metastases is troublesome and inadequate due to limited effects of cytostatic medications and difficult compromises with respect to consequences of radiation and surgery on surrounding brain structures.<br />
<br />
Melanoma has the highest propensity to metastasize to the brain of all cancers. The median survival time with brain metastases is 6 months. The incidence of melanoma has increased over the last 3 decades, and the death rate continues to rise faster than the rate with most cancers. Recent results have shown that it is possible to develop genetically tailored therapy to various sub-populations of patients with metastatic melanoma ('''1-4''').<br />
<br />
Unfortunately, the mechanisms for metastatic spread of melanoma to the brain are largely unknown. This is due to the lack of relevant in vivo model systems. Patients with brain metastases are often excluded from larger clinical trials, leaving us uncertain about the effect of new therapeutic modalities. New research approaches and treatment strategies are clearly needed to improve the outcome for these patients.<br />
<br />
== Project overview ==<br />
<br />
We have developed competitive animal models to study cancer metastasis and especially to the brain. This project includes extensive use of advanced imaging technology (e.g. 7 Tesla MRI, PET and bioluminescence imaging), as well as state of the art genetic and proteomic analyses through close collaboration with national and international core facilities. Our model system has unique translational possibilities in characterizing cancer metastasis and developing new target specific treatment. Biological and therapeutical considerations have motivated us to study melanoma, but any cancer can in principle be studied.<br />
<br />
In our experimental model, cell lines from human melanoma brain metastases and cell lines from primary, cutaneous melanomas are injected into the left cardiac ventricle of immunodeficient mice. In our spontaneous model, the same cell lines are injected into the skin. We have been able to show that these cells form tumors in the mice, and that the metastatic cell populations more aggressively target the brain. Some of this work has already been published ('''5'''). Preliminary results were recently presented at the AACR in the USA, and as a consequence of this, we are now in the process of establishing a cooperation with the manufacturer of one of the most promising new drugs for metastatic melanoma (Vemurafenib/PLX4032; http://www.plexxikon.com) ('''3''').<br />
<br />
[[File:[[File:Figure_1.jpg|200px|thumb|left|alt text]]]]<br />
A. MRI T1 with contrast 6 weeks after intracardial injection showing a contrast-enhancing tumor in the right hemisphere.<br />
B. 3D brain model of the same animal as in A illustrating multiple metastases.<br />
C. Optical imaging 3 weeks after intracardial injection demonstrating both abdominal and brain tumors.<br />
D. Mathematical modeling with automatic quantification of single Fedex labeled cells in the brain based on MRI T2*/MGE sequences.<br />
<br />
It has previously been shown that breast cancer cells prelabelled with micron-sized iron oxide particles (MPIOs) and thereafter injected intracardially into mice, can be tracked by MRI as single cells in the mouse brain ('''6'''). We are currently doing comprehensive MRI studies to elucidate the metastatic patterns and growth potentials of our cell lines by using a similar particle, called Fedex ('''7'''). This work is done in collaboration with Professor Arvid Lundervold at our department. We are able to visualize single cells labelled with Fedex in the animal brains, and through mathematical modelling we can quantify the brain cell load and follow the development of brain metastases, as well as the interesting aspects of tumor dormancy in the brain. This model system gives us a reliable tool, both quantitatively and qualitatively, to study the efficacy of new treatments.<br />
<br />
We are now working to characterize functional and structural differences in the metastatic patterns of cell lines derived from primary tumors and metastases (e.g. by 7 Tesla MRI, PET and bioluminescence imaging). This work will provides us with a groundwork for a more target specific identification and validation of genetic and epigenetic alterations responsible for melanoma disbursement and growth in the brain. Through functional assessments of candidate genes by overexpression and knockout studies, we hope to contribute to the development of more target specific and effective anti-tumor therapy. We are also in the process of investigating the significance of miRNAs in the metastatic process, by selective insertion of candidate miRNAs into the tumor cells.<br />
<br />
== References ==<br />
<br />
(1) Beadling et al. Clin Cancer Res 2008.<br />
(2) Carvajal et al. JAMA 2011.<br />
(3) Chapman et al. N Engl J Med 2011.<br />
(4) Flaherty et al. N Engl J Med 2010.<br />
(5) Wang et al. Neuropathol Appl Neurobiol 2011.<br />
(6) Bos et al. Nature 2009.<br />
(7) Babic et al. Bioconjug Chem 2008.</div>St03724https://wiki.app.uib.no/mriwiki/index.php?title=Terje_Sundstr%C3%B8m_PhD_project&diff=297Terje Sundstrøm PhD project2011-08-28T19:35:48Z<p>St03724: </p>
<hr />
<div>== '''Modeling melanoma brain metastasis: Towards more targeted treatment of cancer''' ==<br />
<br />
== Terje Sundstrøm ==<br />
<br />
Terje Sundstrøm is a MD from the University of Bergen in 2005, and a resident in neurosurgery at Haukeland University Hospital from 2007. As a medical student he started clinical research in neurosurgery. His efforts have so far generated 8 publications on different neurosurgical topics (http://www.uib.no/persons/Terje.Sundstrom). Sundstrøm has during neurosurgical training been recruited to neuro-oncology and translational cancer research. He started his PhD project in January 2011 after receiving a 3-year scholarship from the Western Norway Regional Health Authority. His project on melanoma brain metastasis is a part of the Melanoma Metastasis Project headed by Professor Frits Thorsen, Translational Cancer Research Group, Department of Biomedicine, University of Bergen (http://www.uib.no/persons/Frits.Thorsen).<br />
<br />
== Project background ==<br />
<br />
Metastases are responsible for the vast majority of cancer mortality, and brain metastases occur in 1/3 of adults suffering from cancer. Metastases to the brain are 10 times more frequent than primary brain tumors. The number of patients with brain metastases is increasing because treatments for primary cancers are continually improving, and patients are surviving with these diseases longer. The treatment of brain metastases is troublesome and inadequate due to limited effects of cytostatic medications and difficult compromises with respect to consequences of radiation and surgery on surrounding brain structures.<br />
<br />
Melanoma has the highest propensity to metastasize to the brain of all cancers. The median survival time with brain metastases is 6 months. The incidence of melanoma has increased over the last 3 decades, and the death rate continues to rise faster than the rate with most cancers. Recent results have shown that it is possible to develop genetically tailored therapy to various sub-populations of patients with metastatic melanoma ('''1-4''').<br />
<br />
Unfortunately, the mechanisms for metastatic spread of melanoma to the brain are largely unknown. This is due to the lack of relevant in vivo model systems. Patients with brain metastases are often excluded from larger clinical trials, leaving us uncertain about the effect of new therapeutic modalities. New research approaches and treatment strategies are clearly needed to improve the outcome for these patients.<br />
<br />
== Project overview ==<br />
<br />
We have developed competitive animal models to study cancer metastasis and especially to the brain. This project includes extensive use of advanced imaging technology (e.g. 7 Tesla MRI, PET and bioluminescence imaging), as well as state of the art genetic and proteomic analyses through close collaboration with national and international core facilities. Our model system has unique translational possibilities in characterizing cancer metastasis and developing new target specific treatment. Biological and therapeutical considerations have motivated us to study melanoma, but any cancer can in principle be studied.<br />
<br />
In our experimental model, cell lines from human melanoma brain metastases and cell lines from primary, cutaneous melanomas are injected into the left cardiac ventricle of immunodeficient mice. In our spontaneous model, the same cell lines are injected into the skin. We have been able to show that these cells form tumors in the mice, and that the metastatic cell populations more aggressively target the brain. Some of this work has already been published ('''5'''). Preliminary results were recently presented at the AACR in the USA, and as a consequence of this, we are now in the process of establishing a cooperation with the manufacturer of one of the most promising new drugs for metastatic melanoma (Vemurafenib/PLX4032; http://www.plexxikon.com) ('''3''').<br />
<br />
[[File:[[File:Figure_1.jpg|200px|thumb|left|alt text]]]]<br />
<br />
It has previously been shown that breast cancer cells prelabelled with micron-sized iron oxide particles (MPIOs) and thereafter injected intracardially into mice, can be tracked by MRI as single cells in the mouse brain ('''6'''). We are currently doing comprehensive MRI studies to elucidate the metastatic patterns and growth potentials of our cell lines by using a similar particle, called Fedex ('''7'''). This work is done in collaboration with Professor Arvid Lundervold at our department. We are able to visualize single cells labelled with Fedex in the animal brains, and through mathematical modelling we can quantify the brain cell load and follow the development of brain metastases, as well as the interesting aspects of tumor dormancy in the brain. This model system gives us a reliable tool, both quantitatively and qualitatively, to study the efficacy of new treatments.<br />
<br />
== Figure 1 Modeling melanoma brain metastasis in the mouse ==<br />
<br />
[[File:Figure_1.jpg]]<br />
<br />
A. MRI T1 with contrast 6 weeks after intracardial injection showing a contrast-enhancing tumor in the right hemisphere.<br />
B. 3D brain model of the same animal as in A illustrating multiple metastases.<br />
C. Optical imaging 3 weeks after intracardial injection demonstrating both abdominal and brain tumors.<br />
D. Mathematical modeling with automatic quantification of single Fedex labeled cells in the brain based on MRI T2*/MGE sequences.<br />
<br />
We are now working to characterize functional and structural differences in the metastatic patterns of cell lines derived from primary tumors and metastases (e.g. by 7 Tesla MRI, PET and bioluminescence imaging). This work will provides us with a groundwork for a more target specific identification and validation of genetic and epigenetic alterations responsible for melanoma disbursement and growth in the brain. Through functional assessments of candidate genes by overexpression and knockout studies, we hope to contribute to the development of more target specific and effective anti-tumor therapy. We are also in the process of investigating the significance of miRNAs in the metastatic process, by selective insertion of candidate miRNAs into the tumor cells.<br />
<br />
== References ==<br />
<br />
(1) Beadling et al. Clin Cancer Res 2008.<br />
(2) Carvajal et al. JAMA 2011.<br />
(3) Chapman et al. N Engl J Med 2011.<br />
(4) Flaherty et al. N Engl J Med 2010.<br />
(5) Wang et al. Neuropathol Appl Neurobiol 2011.<br />
(6) Bos et al. Nature 2009.<br />
(7) Babic et al. Bioconjug Chem 2008.</div>St03724https://wiki.app.uib.no/mriwiki/index.php?title=Terje_Sundstr%C3%B8m_PhD_project&diff=296Terje Sundstrøm PhD project2011-08-28T19:34:25Z<p>St03724: </p>
<hr />
<div>== '''Modeling melanoma brain metastasis: Towards more targeted treatment of cancer''' ==<br />
<br />
== Terje Sundstrøm ==<br />
<br />
Terje Sundstrøm is a MD from the University of Bergen in 2005, and a resident in neurosurgery at Haukeland University Hospital from 2007. As a medical student he started clinical research in neurosurgery. His efforts have so far generated 8 publications on different neurosurgical topics (http://www.uib.no/persons/Terje.Sundstrom). Sundstrøm has during neurosurgical training been recruited to neuro-oncology and translational cancer research. He started his PhD project in January 2011 after receiving a 3-year scholarship from the Western Norway Regional Health Authority. His project on melanoma brain metastasis is a part of the Melanoma Metastasis Project headed by Professor Frits Thorsen, Translational Cancer Research Group, Department of Biomedicine, University of Bergen (http://www.uib.no/persons/Frits.Thorsen).<br />
<br />
== Project background ==<br />
<br />
Metastases are responsible for the vast majority of cancer mortality, and brain metastases occur in 1/3 of adults suffering from cancer. Metastases to the brain are 10 times more frequent than primary brain tumors. The number of patients with brain metastases is increasing because treatments for primary cancers are continually improving, and patients are surviving with these diseases longer. The treatment of brain metastases is troublesome and inadequate due to limited effects of cytostatic medications and difficult compromises with respect to consequences of radiation and surgery on surrounding brain structures.<br />
<br />
Melanoma has the highest propensity to metastasize to the brain of all cancers. The median survival time with brain metastases is 6 months. The incidence of melanoma has increased over the last 3 decades, and the death rate continues to rise faster than the rate with most cancers. Recent results have shown that it is possible to develop genetically tailored therapy to various sub-populations of patients with metastatic melanoma ('''1-4''').<br />
<br />
Unfortunately, the mechanisms for metastatic spread of melanoma to the brain are largely unknown. This is due to the lack of relevant in vivo model systems. Patients with brain metastases are often excluded from larger clinical trials, leaving us uncertain about the effect of new therapeutic modalities. New research approaches and treatment strategies are clearly needed to improve the outcome for these patients.<br />
<br />
== Project overview ==<br />
<br />
We have developed competitive animal models to study cancer metastasis and especially to the brain. This project includes extensive use of advanced imaging technology (e.g. 7 Tesla MRI, PET and bioluminescence imaging), as well as state of the art genetic and proteomic analyses through close collaboration with national and international core facilities. Our model system has unique translational possibilities in characterizing cancer metastasis and developing new target specific treatment. Biological and therapeutical considerations have motivated us to study melanoma, but any cancer can in principle be studied.<br />
<br />
In our experimental model, cell lines from human melanoma brain metastases and cell lines from primary, cutaneous melanomas are injected into the left cardiac ventricle of immunodeficient mice. In our spontaneous model, the same cell lines are injected into the skin. We have been able to show that these cells form tumors in the mice, and that the metastatic cell populations more aggressively target the brain. Some of this work has already been published ('''5'''). Preliminary results were recently presented at the AACR in the USA, and as a consequence of this, we are now in the process of establishing a cooperation with the manufacturer of one of the most promising new drugs for metastatic melanoma (Vemurafenib/PLX4032; http://www.plexxikon.com) ('''3''').<br />
<br />
It has previously been shown that breast cancer cells prelabelled with micron-sized iron oxide particles (MPIOs) and thereafter injected intracardially into mice, can be tracked by MRI as single cells in the mouse brain ('''6'''). We are currently doing comprehensive MRI studies to elucidate the metastatic patterns and growth potentials of our cell lines by using a similar particle, called Fedex ('''7'''). This work is done in collaboration with Professor Arvid Lundervold at our department. We are able to visualize single cells labelled with Fedex in the animal brains, and through mathematical modelling we can quantify the brain cell load and follow the development of brain metastases, as well as the interesting aspects of tumor dormancy in the brain. This model system gives us a reliable tool, both quantitatively and qualitatively, to study the efficacy of new treatments.<br />
<br />
== Figure 1 Modeling melanoma brain metastasis in the mouse ==<br />
<br />
[[File:Figure_1.jpg]]<br />
<br />
A. MRI T1 with contrast 6 weeks after intracardial injection showing a contrast-enhancing tumor in the right hemisphere.<br />
B. 3D brain model of the same animal as in A illustrating multiple metastases.<br />
C. Optical imaging 3 weeks after intracardial injection demonstrating both abdominal and brain tumors.<br />
D. Mathematical modeling with automatic quantification of single Fedex labeled cells in the brain based on MRI T2*/MGE sequences.<br />
<br />
We are now working to characterize functional and structural differences in the metastatic patterns of cell lines derived from primary tumors and metastases (e.g. by 7 Tesla MRI, PET and bioluminescence imaging). This work will provides us with a groundwork for a more target specific identification and validation of genetic and epigenetic alterations responsible for melanoma disbursement and growth in the brain. Through functional assessments of candidate genes by overexpression and knockout studies, we hope to contribute to the development of more target specific and effective anti-tumor therapy. We are also in the process of investigating the significance of miRNAs in the metastatic process, by selective insertion of candidate miRNAs into the tumor cells.<br />
<br />
== References ==<br />
<br />
(1) Beadling et al. Clin Cancer Res 2008.<br />
(2) Carvajal et al. JAMA 2011.<br />
(3) Chapman et al. N Engl J Med 2011.<br />
(4) Flaherty et al. N Engl J Med 2010.<br />
(5) Wang et al. Neuropathol Appl Neurobiol 2011.<br />
(6) Bos et al. Nature 2009.<br />
(7) Babic et al. Bioconjug Chem 2008.</div>St03724https://wiki.app.uib.no/mriwiki/index.php?title=Terje_Sundstr%C3%B8m_PhD_project&diff=295Terje Sundstrøm PhD project2011-08-28T19:31:53Z<p>St03724: </p>
<hr />
<div>== '''Modeling melanoma brain metastasis: Towards more targeted treatment of cancer''' ==<br />
<br />
== Terje Sundstrøm ==<br />
<br />
Terje Sundstrøm is a MD from the University of Bergen in 2005, and a resident in neurosurgery at Haukeland University Hospital from 2007. As a medical student he started clinical research in neurosurgery. His efforts have so far generated 8 publications on different neurosurgical topics (http://www.uib.no/persons/Terje.Sundstrom). The applicant has during neurosurgical training been recruited to neuro-oncology and translational cancer research. Sundstrøm started his PhD project in January 2011 after receiving a 3-year scholarship from the Western Norway Regional Health Authority. His project on melanoma brain metastasis is a part of the Melanoma Metastasis Project headed by Professor Frits Thorsen, Translational Cancer Research Group, Department of Biomedicine, University of Bergen (http://www.uib.no/persons/Frits.Thorsen).<br />
<br />
== Project background ==<br />
<br />
Metastases are responsible for the vast majority of cancer mortality, and brain metastases occur in 1/3 of adults suffering from cancer. Metastases to the brain are 10 times more frequent than primary brain tumors. The number of patients with brain metastases is increasing because treatments for primary cancers are continually improving, and patients are surviving with these diseases longer. The treatment of brain metastases is troublesome and inadequate due to limited effects of cytostatic medications and difficult compromises with respect to consequences of radiation and surgery on surrounding brain structures.<br />
<br />
Melanoma has the highest propensity to metastasize to the brain of all cancers. The median survival time with brain metastases is 6 months. The incidence of melanoma has increased over the last 3 decades, and the death rate continues to rise faster than the rate with most cancers. Recent results have shown that it is possible to develop genetically tailored therapy to various sub-populations of patients with metastatic melanoma ('''1-4''').<br />
<br />
Unfortunately, the mechanisms for metastatic spread of melanoma to the brain are largely unknown. This is due to the lack of relevant in vivo model systems. Patients with brain metastases are often excluded from larger clinical trials, leaving us uncertain about the effect of new therapeutic modalities. New research approaches and treatment strategies are clearly needed to improve the outcome for these patients.<br />
<br />
== Project overview ==<br />
<br />
We have developed competitive animal models to study cancer metastasis and especially to the brain. This project includes extensive use of advanced imaging technology (e.g. 7 Tesla MRI, PET and bioluminescence imaging), as well as state of the art genetic and proteomic analyses through close collaboration with national and international core facilities. Our model system has unique translational possibilities in characterizing cancer metastasis and developing new target specific treatment. Biological and therapeutical considerations have motivated us to study melanoma, but any cancer can in principle be studied. <br />
<br />
In our experimental model, cell lines from human melanoma brain metastases and cell lines from primary, cutaneous melanomas are injected into the left cardiac ventricle of immunodeficient mice. In our spontaneous model, the same cell lines are injected into the skin. We have been able to show that these cells form tumors in the mice, and that the metastatic cell populations more aggressively target the brain. Some of this work has already been published ('''5'''). Preliminary results were recently presented at the AACR in the USA, and as a consequence of this, we are now in the process of establishing a cooperation with the manufacturer of one of the most promising new drugs for metastatic melanoma (Vemurafenib/PLX4032; http://www.plexxikon.com) ('''3''').<br />
<br />
It has previously been shown that breast cancer cells prelabelled with micron-sized iron oxide particles (MPIOs) and thereafter injected intracardially into mice, can be tracked by MRI as single cells in the mouse brain ('''6'''). We are currently doing comprehensive MRI studies to elucidate the metastatic patterns and growth potentials of our cell lines by using a similar particle, called Fedex ('''7'''). This work is done in collaboration with Professor Arvid Lundervold at our department. We are able to visualize single cells labelled with Fedex in the animal brains, and through mathematical modelling we can quantify the brain cell load and follow the development of brain metastases, as well as the interesting aspects of tumor dormancy in the brain. This model system gives us a reliable tool, both quantitatively and qualitatively, to study the efficacy of new treatments.<br />
<br />
== Figure 1 Modeling melanoma brain metastasis in the mouse ==<br />
<br />
[[File:Figure_1.jpg]]<br />
<br />
A. MRI T1 with contrast 6 weeks after intracardial injection showing a contrast-enhancing tumor in the right hemisphere.<br />
B. 3D brain model of the same animal as in A illustrating multiple metastases.<br />
C. Optical imaging 3 weeks after intracardial injection demonstrating both abdominal and brain tumors.<br />
D. Mathematical modeling with automatic quantification of single Fedex labeled cells in the brain based on MRI T2*/MGE sequences.<br />
<br />
We are now working to characterize functional and structural differences in the metastatic patterns of cell lines derived from primary tumors and metastases (e.g. by 7 Tesla MRI, PET and bioluminescence imaging). This work will provides us with a groundwork for a more target specific identification and validation of genetic and epigenetic alterations responsible for melanoma disbursement and growth in the brain. Through functional assessments of candidate genes by overexpression and knockout studies, we hope to contribute to the development of more target specific and effective anti-tumor therapy. We are also in the process of investigating the significance of miRNAs in the metastatic process, by selective insertion of candidate miRNAs into the tumor cells.<br />
<br />
== References ==<br />
<br />
(1) Beadling et al. Clin Cancer Res 2008.<br />
(2) Carvajal et al. JAMA 2011.<br />
(3) Chapman et al. N Engl J Med 2011.<br />
(4) Flaherty et al. N Engl J Med 2010.<br />
(5) Wang et al. Neuropathol Appl Neurobiol 2011.<br />
(6) Bos et al. Nature 2009.<br />
(7) Babic et al. Bioconjug Chem 2008.</div>St03724https://wiki.app.uib.no/mriwiki/index.php?title=Terje_Sundstr%C3%B8m_PhD_project&diff=294Terje Sundstrøm PhD project2011-08-28T19:28:57Z<p>St03724: </p>
<hr />
<div>== '''Modeling melanoma brain metastasis: Towards more targeted treatment of cancer''' ==<br />
<br />
== Terje Sundstrøm ==<br />
<br />
Terje Sundstrøm is a MD from the University of Bergen in 2005, and a resident in neurosurgery at Haukeland University Hospital from 2007. As a medical student he started clinical research in neurosurgery. His efforts have so far generated 8 publications on different neurosurgical topics (http://www.uib.no/persons/Terje.Sundstrom). The applicant has during neurosurgical training been recruited to neuro-oncology and translational cancer research. Sundstrøm started his PhD project in January 2011 after receiving a 3-year scholarship from the Western Norway Regional Health Authority. His project on melanoma brain metastasis is a part of the Melanoma Metastasis Project headed by Professor Frits Thorsen, Translational Cancer Research Group, Department of Biomedicine, University of Bergen (http://www.uib.no/persons/Frits.Thorsen).<br />
<br />
== Project background ==<br />
<br />
Metastases are responsible for the vast majority of cancer mortality, and brain metastases occur in 1/3 of adults suffering from cancer. Metastases to the brain are 10 times more frequent than primary brain tumors. The number of patients with brain metastases is increasing because treatments for primary cancers are continually improving, and patients are surviving with these diseases longer. The treatment of brain metastases is troublesome and inadequate due to limited effects of cytostatic medications and difficult compromises with respect to consequences of radiation and surgery on surrounding brain structures.<br />
<br />
Melanoma has the highest propensity to metastasize to the brain of all cancers. The median survival time with brain metastases is 6 months. The incidence of melanoma has increased over the last 3 decades, and the death rate continues to rise faster than the rate with most cancers. Recent results have shown that it is possible to develop genetically tailored therapy to various sub-populations of patients with metastatic melanoma ('''1-4''').<br />
<br />
Unfortunately, the mechanisms for metastatic spread of melanoma to the brain are largely unknown. This is due to the lack of relevant in vivo model systems. Patients with brain metastases are often excluded from larger clinical trials, leaving us uncertain about the effect of new therapeutic modalities. New research approaches and treatment strategies are clearly needed to improve the outcome for these patients.<br />
<br />
== Project overview ==<br />
<br />
We have developed competitive animal models to study cancer metastasis and especially to the brain. This project includes extensive use of advanced imaging technology (e.g. 7 Tesla MRI, PET and bioluminescence imaging), as well as state of the art genetic and proteomic analyses through close collaboration with national and international core facilities. Our model system has unique translational possibilities in characterizing cancer metastasis and developing new target specific treatment. Biological and therapeutical considerations have motivated us to study melanoma, but any cancer can in principle be studied. <br />
<br />
In our experimental model, cell lines from human melanoma brain metastases and cell lines from primary, cutaneous melanomas are injected into the left cardiac ventricle of immunodeficient mice. In our spontaneous model, the same cell lines are injected into the skin. We have been able to show that these cells form tumors in the mice, and that the metastatic cell populations more aggressively target the brain. Some of this work has already been published ('''5'''). Preliminary results were recently presented at the AACR in the USA, and as a consequence of this, we are now in the process of establishing a cooperation with the manufacturer of one of the most promising new drugs for metastatic melanoma (Vemurafenib/PLX4032; http://www.plexxikon.com) ('''3''').<br />
<br />
It has previously been shown that breast cancer cells prelabelled with micron-sized iron oxide particles (MPIOs) and thereafter injected intracardially into mice, can be tracked by MRI as single cells in the mouse brain ('''6'''). We are currently doing comprehensive MRI studies to elucidate the metastatic patterns and growth potentials of our cell lines by using a similar particle, called Fedex ('''7'''). This work is done in collaboration with Professor Arvid Lundervold at our department. We are able to visualize single cells labelled with Fedex in the animal brains, and through mathematical modelling we can quantify the brain cell load and follow the development of brain metastases, as well as the interesting aspects of tumor dormancy in the brain. This model system gives us a reliable tool, both quantitatively and qualitatively, to study the efficacy of new treatments.<br />
<br />
[[File:Figure_1.jpg]]<br />
'''Figure 1 Modeling melanoma brain metastasis in the mouse'''<br />
A. MRI T1 with contrast 6 weeks after intracardial injection showing a contrast-enhancing tumor in the right hemisphere.<br />
B. 3D brain model of the same animal as in A illustrating multiple metastases.<br />
C. Optical imaging 3 weeks after intracardial injection demonstrating both abdominal and brain tumors.<br />
D. Mathematical modeling with automatic quantification of single Fedex labeled cells in the brain based on MRI T2*/MGE sequences.<br />
<br />
We have developed cell lines from 7 human melanoma metastases. We are now working to characterize functional and structural differences in the metastatic patterns of cell lines derived from primary tumors and metastases (e.g. by 7 Tesla MRI, PET and bioluminescence imaging). This work will provides us with a groundwork for a more target specific identification and validation of genetic and epigenetic alterations responsible for melanoma disbursement and growth in the brain. Through functional assessments of candidate genes by overexpression and knockout studies, we hope to contribute to the development of more target specific and effective anti-tumor therapy. We are also in the process of investigating the significance of miRNAs in the metastatic process, by selective insertion of candidate miRNAs into the tumor cells.<br />
<br />
== References ==<br />
<br />
(1) Beadling et al. Clin Cancer Res 2008.<br />
(2) Carvajal et al. JAMA 2011.<br />
(3) Chapman et al. N Engl J Med 2011.<br />
(4) Flaherty et al. N Engl J Med 2010.<br />
(5) Wang et al. Neuropathol Appl Neurobiol 2011.<br />
(6) Bos et al. Nature 2009.<br />
(7) Babic et al. Bioconjug Chem 2008.</div>St03724https://wiki.app.uib.no/mriwiki/index.php?title=Terje_Sundstr%C3%B8m_PhD_project&diff=293Terje Sundstrøm PhD project2011-08-28T19:27:24Z<p>St03724: </p>
<hr />
<div>== '''Modeling melanoma brain metastasis: Towards more targeted treatment of cancer''' ==<br />
<br />
== Terje Sundstrøm ==<br />
<br />
Terje Sundstrøm is a MD from the University of Bergen in 2005, and a resident in neurosurgery at Haukeland University Hospital from 2007. As a medical student he started clinical research in neurosurgery. His efforts have so far generated 8 publications on different neurosurgical topics (http://www.uib.no/persons/Terje.Sundstrom). The applicant has during neurosurgical training been recruited to neuro-oncology and translational cancer research. Sundstrøm started his PhD project in January 2011 after receiving a 3-year scholarship from the Western Norway Regional Health Authority. His project on melanoma brain metastasis is a part of the Melanoma Metastasis Project headed by Professor Frits Thorsen, Translational Cancer Research Group, Department of Biomedicine, University of Bergen (http://www.uib.no/persons/Frits.Thorsen).<br />
<br />
== Project background ==<br />
<br />
Metastases are responsible for the vast majority of cancer mortality, and brain metastases occur in 1/3 of adults suffering from cancer. Metastases to the brain are 10 times more frequent than primary brain tumors. The number of patients with brain metastases is increasing because treatments for primary cancers are continually improving, and patients are surviving with these diseases longer. The treatment of brain metastases is troublesome and inadequate due to limited effects of cytostatic medications and difficult compromises with respect to consequences of radiation and surgery on surrounding brain structures.<br />
<br />
Melanoma has the highest propensity to metastasize to the brain of all cancers. The median survival time with brain metastases is 6 months. The incidence of melanoma has increased over the last 3 decades, and the death rate continues to rise faster than the rate with most cancers. Recent results have shown that it is possible to develop genetically tailored therapy to various sub-populations of patients with metastatic melanoma ('''1-4''').<br />
<br />
Unfortunately, the mechanisms for metastatic spread of melanoma to the brain are largely unknown. This is due to the lack of relevant in vivo model systems. Patients with brain metastases are often excluded from larger clinical trials, leaving us uncertain about the effect of new therapeutic modalities. New research approaches and treatment strategies are clearly needed to improve the outcome for these patients.<br />
<br />
== Project overview ==<br />
<br />
We have developed competitive animal models to study cancer metastasis and especially to the brain. This project includes extensive use of advanced imaging technology (e.g. 7 Tesla MRI, PET and bioluminescence imaging), as well as state of the art genetic and proteomic analyses through close collaboration with national and international core facilities. Our model system has unique translational possibilities in characterizing cancer metastasis and developing new target specific treatment. Biological and therapeutical considerations have motivated us to study melanoma, but any cancer can in principle be studied. <br />
<br />
In our experimental model, cell lines from human melanoma brain metastases and cell lines from primary, cutaneous melanomas are injected into the left cardiac ventricle of immunodeficient mice. In our spontaneous model, the same cell lines are injected into the skin. We have been able to show that these cells form tumors in the mice, and that the metastatic cell populations more aggressively target the brain. Some of this work has already been published ('''5'''). Preliminary results were recently presented at the AACR in the USA, and as a consequence of this, we are now in the process of establishing a cooperation with the manufacturer of one of the most promising new drugs for metastatic melanoma (Vemurafenib/PLX4032; http://www.plexxikon.com) ('''3''').<br />
<br />
It has previously been shown that breast cancer cells prelabelled with micron-sized iron oxide particles (MPIOs) and thereafter injected intracardially into mice, can be tracked by MRI as single cells in the mouse brain ('''6'''). We are currently doing comprehensive MRI studies to elucidate the metastatic patterns and growth potentials of our cell lines by using a similar particle, called Fedex ('''7'''). This work is done in collaboration with Professor Arvid Lundervold at our department. We are able to visualize single cells labelled with Fedex in the animal brains, and through mathematical modelling we can quantify the brain cell load and follow the development of brain metastases, as well as the interesting aspects of tumor dormancy in the brain. This model system gives us a reliable tool, both quantitatively and qualitatively, to study the efficacy of new treatments.<br />
<br />
[[File:[[File:Figure_1.jpg]]]]<br />
'''Figure 1 Modeling melanoma brain metastasis in the mouse'''<br />
A. MRI T1 with contrast 6 weeks after intracardial injection showing a contrast-enhancing tumor in the right hemisphere.<br />
B. 3D brain model of the same animal as in A illustrating multiple metastases.<br />
C. Optical imaging 3 weeks after intracardial injection demonstrating both abdominal and brain tumors.<br />
D. Mathematical modeling with automatic quantification of single Fedex labeled cells in the brain based on MRI T2*/MGE sequences.<br />
<br />
We have developed cell lines from 7 human melanoma metastases. We are now working to characterize functional and structural differences in the metastatic patterns of cell lines derived from primary tumors and metastases (e.g. by 7 Tesla MRI, PET and bioluminescence imaging). This work will provides us with a groundwork for a more target specific identification and validation of genetic and epigenetic alterations responsible for melanoma disbursement and growth in the brain. Through functional assessments of candidate genes by overexpression and knockout studies, we hope to contribute to the development of more target specific and effective anti-tumor therapy. We are also in the process of investigating the significance of miRNAs in the metastatic process, by selective insertion of candidate miRNAs into the tumor cells.<br />
<br />
== References ==<br />
<br />
(1) Beadling et al. Clin Cancer Res 2008.<br />
(2) Carvajal et al. JAMA 2011.<br />
(3) Chapman et al. N Engl J Med 2011.<br />
(4) Flaherty et al. N Engl J Med 2010.<br />
(5) Wang et al. Neuropathol Appl Neurobiol 2011.<br />
(6) Bos et al. Nature 2009.<br />
(7) Babic et al. Bioconjug Chem 2008.</div>St03724https://wiki.app.uib.no/mriwiki/index.php?title=Terje_Sundstr%C3%B8m_PhD_project&diff=292Terje Sundstrøm PhD project2011-08-28T19:25:59Z<p>St03724: </p>
<hr />
<div>== '''Modeling melanoma brain metastasis: Towards more targeted treatment of cancer''' ==<br />
<br />
== Terje Sundstrøm ==<br />
<br />
Terje Sundstrøm is a MD from the University of Bergen in 2005, and a resident in neurosurgery at Haukeland University Hospital from 2007. As a medical student he started clinical research in neurosurgery. His efforts have so far generated 8 publications on different neurosurgical topics (http://www.uib.no/persons/Terje.Sundstrom). The applicant has during neurosurgical training been recruited to neuro-oncology and translational cancer research. Sundstrøm started his PhD project in January 2011 after receiving a 3-year scholarship from the Western Norway Regional Health Authority. His project on melanoma brain metastasis is a part of the Melanoma Metastasis Project headed by Professor Frits Thorsen, Translational Cancer Research Group, Department of Biomedicine, University of Bergen (http://www.uib.no/persons/Frits.Thorsen).<br />
<br />
== Project background ==<br />
<br />
Metastases are responsible for the vast majority of cancer mortality, and brain metastases occur in 1/3 of adults suffering from cancer. Metastases to the brain are 10 times more frequent than primary brain tumors. The number of patients with brain metastases is increasing because treatments for primary cancers are continually improving, and patients are surviving with these diseases longer. The treatment of brain metastases is troublesome and inadequate due to limited effects of cytostatic medications and difficult compromises with respect to consequences of radiation and surgery on surrounding brain structures.<br />
<br />
Melanoma has the highest propensity to metastasize to the brain of all cancers. The median survival time with brain metastases is 6 months. The incidence of melanoma has increased over the last 3 decades, and the death rate continues to rise faster than the rate with most cancers. Recent results have shown that it is possible to develop genetically tailored therapy to various sub-populations of patients with metastatic melanoma ('''1-4''').<br />
<br />
Unfortunately, the mechanisms for metastatic spread of melanoma to the brain are largely unknown. This is due to the lack of relevant in vivo model systems. Patients with brain metastases are often excluded from larger clinical trials, leaving us uncertain about the effect of new therapeutic modalities. New research approaches and treatment strategies are clearly needed to improve the outcome for these patients.<br />
<br />
== Project overview ==<br />
<br />
We have developed competitive animal models to study cancer metastasis and especially to the brain. This project includes extensive use of advanced imaging technology (e.g. 7 Tesla MRI, PET and bioluminescence imaging), as well as state of the art genetic and proteomic analyses through close collaboration with national and international core facilities. Our model system has unique translational possibilities in characterizing cancer metastasis and developing new target specific treatment. Biological and therapeutical considerations have motivated us to study melanoma, but any cancer can in principle be studied. <br />
<br />
In our experimental model, cell lines from human melanoma brain metastases and cell lines from primary, cutaneous melanomas are injected into the left cardiac ventricle of immunodeficient mice. In our spontaneous model, the same cell lines are injected into the skin. We have been able to show that these cells form tumors in the mice, and that the metastatic cell populations more aggressively target the brain. Some of this work has already been published ('''5'''). Preliminary results were recently presented at the AACR in the USA, and as a consequence of this, we are now in the process of establishing a cooperation with the manufacturer of one of the most promising new drugs for metastatic melanoma (Vemurafenib/PLX4032; http://www.plexxikon.com) ('''3''').<br />
<br />
It has previously been shown that breast cancer cells prelabelled with micron-sized iron oxide particles (MPIOs) and thereafter injected intracardially into mice, can be tracked by MRI as single cells in the mouse brain ('''6'''). We are currently doing comprehensive MRI studies to elucidate the metastatic patterns and growth potentials of our cell lines by using a similar particle, called Fedex ('''7'''). This work is done in collaboration with Professor Arvid Lundervold at our department. We are able to visualize single cells labelled with Fedex in the animal brains, and through mathematical modelling we can quantify the brain cell load and follow the development of brain metastases, as well as the interesting aspects of tumor dormancy in the brain. This model system gives us a reliable tool, both quantitatively and qualitatively, to study the efficacy of new treatments.<br />
<br />
[[File:[[File:Figure_1.jpg]]]]<br />
<br />
We have developed cell lines from 7 human melanoma metastases. We are now working to characterize functional and structural differences in the metastatic patterns of cell lines derived from primary tumors and metastases (e.g. by 7 Tesla MRI, PET and bioluminescence imaging). This work will provides us with a groundwork for a more target specific identification and validation of genetic and epigenetic alterations responsible for melanoma disbursement and growth in the brain. Through functional assessments of candidate genes by overexpression and knockout studies, we hope to contribute to the development of more target specific and effective anti-tumor therapy. We are also in the process of investigating the significance of miRNAs in the metastatic process, by selective insertion of candidate miRNAs into the tumor cells.<br />
<br />
== References ==<br />
<br />
(1) Beadling et al. Clin Cancer Res 2008.<br />
(2) Carvajal et al. JAMA 2011.<br />
(3) Chapman et al. N Engl J Med 2011.<br />
(4) Flaherty et al. N Engl J Med 2010.<br />
(5) Wang et al. Neuropathol Appl Neurobiol 2011.<br />
(6) Bos et al. Nature 2009.<br />
(7) Babic et al. Bioconjug Chem 2008.</div>St03724https://wiki.app.uib.no/mriwiki/index.php?title=Terje_Sundstr%C3%B8m_PhD_project&diff=291Terje Sundstrøm PhD project2011-08-28T19:24:44Z<p>St03724: </p>
<hr />
<div>== '''Modeling melanoma brain metastasis: Towards more targeted treatment of cancer''' ==<br />
<br />
== Terje Sundstrøm ==<br />
<br />
Terje Sundstrøm is a MD from the University of Bergen in 2005, and a resident in neurosurgery at Haukeland University Hospital from 2007. As a medical student he started clinical research in neurosurgery. His efforts have so far generated 8 publications on different neurosurgical topics (http://www.uib.no/persons/Terje.Sundstrom). The applicant has during neurosurgical training been recruited to neuro-oncology and translational cancer research. Sundstrøm started his PhD project in January 2011 after receiving a 3-year scholarship from the Western Norway Regional Health Authority. His project on melanoma brain metastasis is a part of the Melanoma Metastasis Project headed by Professor Frits Thorsen, Translational Cancer Research Group, Department of Biomedicine, University of Bergen (http://www.uib.no/persons/Frits.Thorsen).<br />
<br />
== Project background ==<br />
<br />
Metastases are responsible for the vast majority of cancer mortality, and brain metastases occur in 1/3 of adults suffering from cancer. Metastases to the brain are 10 times more frequent than primary brain tumors. The number of patients with brain metastases is increasing because treatments for primary cancers are continually improving, and patients are surviving with these diseases longer. The treatment of brain metastases is troublesome and inadequate due to limited effects of cytostatic medications and difficult compromises with respect to consequences of radiation and surgery on surrounding brain structures.<br />
<br />
Melanoma has the highest propensity to metastasize to the brain of all cancers. The median survival time with brain metastases is 6 months. The incidence of melanoma has increased over the last 3 decades, and the death rate continues to rise faster than the rate with most cancers. Recent results have shown that it is possible to develop genetically tailored therapy to various sub-populations of patients with metastatic melanoma ('''1-4''').<br />
<br />
Unfortunately, the mechanisms for metastatic spread of melanoma to the brain are largely unknown. This is due to the lack of relevant in vivo model systems. Patients with brain metastases are often excluded from larger clinical trials, leaving us uncertain about the effect of new therapeutic modalities. New research approaches and treatment strategies are clearly needed to improve the outcome for these patients.<br />
<br />
== Project overview ==<br />
<br />
We have developed competitive animal models to study cancer metastasis and especially to the brain. This project includes extensive use of advanced imaging technology (e.g. 7 Tesla MRI, PET and bioluminescence imaging), as well as state of the art genetic and proteomic analyses through close collaboration with national and international core facilities. Our model system has unique translational possibilities in characterizing cancer metastasis and developing new target specific treatment. Biological and therapeutical considerations have motivated us to study melanoma, but any cancer can in principle be studied. <br />
<br />
In our experimental model, cell lines from human melanoma brain metastases and cell lines from primary, cutaneous melanomas are injected into the left cardiac ventricle of immunodeficient mice. In our spontaneous model, the same cell lines are injected into the skin. We have been able to show that these cells form tumors in the mice, and that the metastatic cell populations more aggressively target the brain. Some of this work has already been published ('''5'''). Preliminary results were recently presented at the AACR in the USA, and as a consequence of this, we are now in the process of establishing a cooperation with the manufacturer of one of the most promising new drugs for metastatic melanoma (Vemurafenib/PLX4032; http://www.plexxikon.com) ('''3''').<br />
<br />
It has previously been shown that breast cancer cells prelabelled with micron-sized iron oxide particles (MPIOs) and thereafter injected intracardially into mice, can be tracked by MRI as single cells in the mouse brain ('''6'''). We are currently doing comprehensive MRI studies to elucidate the metastatic patterns and growth potentials of our cell lines by using a similar particle, called Fedex ('''7'''). This work is done in collaboration with Professor Arvid Lundervold at our department. We are able to visualize single cells labelled with Fedex in the animal brains, and through mathematical modelling we can quantify the brain cell load and follow the development of brain metastases, as well as the interesting aspects of tumor dormancy in the brain. This model system gives us a reliable tool, both quantitatively and qualitatively, to study the efficacy of new treatments.<br />
<br />
<br />
<br />
We have developed cell lines from 7 human melanoma metastases. We are now working to characterize functional and structural differences in the metastatic patterns of cell lines derived from primary tumors and metastases (e.g. by 7 Tesla MRI, PET and bioluminescence imaging). This work will provides us with a groundwork for a more target specific identification and validation of genetic and epigenetic alterations responsible for melanoma disbursement and growth in the brain. Through functional assessments of candidate genes by overexpression and knockout studies, we hope to contribute to the development of more target specific and effective anti-tumor therapy. We are also in the process of investigating the significance of miRNAs in the metastatic process, by selective insertion of candidate miRNAs into the tumor cells.<br />
<br />
== References ==<br />
<br />
(1) Beadling et al. Clin Cancer Res 2008.<br />
(2) Carvajal et al. JAMA 2011.<br />
(3) Chapman et al. N Engl J Med 2011.<br />
(4) Flaherty et al. N Engl J Med 2010.<br />
(5) Wang et al. Neuropathol Appl Neurobiol 2011.<br />
(6) Bos et al. Nature 2009.<br />
(7) Babic et al. Bioconjug Chem 2008.</div>St03724https://wiki.app.uib.no/mriwiki/index.php?title=Terje_Sundstr%C3%B8m_PhD_project&diff=290Terje Sundstrøm PhD project2011-08-28T19:24:05Z<p>St03724: </p>
<hr />
<div>== '''Modeling melanoma brain metastasis: Towards more targeted treatment of cancer''' ==<br />
<br />
== Terje Sundstrøm ==<br />
<br />
Terje Sundstrøm is a MD from the University of Bergen in 2005, and a resident in neurosurgery at Haukeland University Hospital from 2007. As a medical student he started clinical research in neurosurgery. His efforts have so far generated 8 publications on different neurosurgical topics (http://www.uib.no/persons/Terje.Sundstrom). The applicant has during neurosurgical training been recruited to neuro-oncology and translational cancer research. Sundstrøm started his PhD project in January 2011 after receiving a 3-year scholarship from the Western Norway Regional Health Authority. His project on melanoma brain metastasis is a part of the Melanoma Metastasis Project headed by Professor Frits Thorsen, Translational Cancer Research Group, Department of Biomedicine, University of Bergen (http://www.uib.no/persons/Frits.Thorsen).<br />
<br />
== Project background ==<br />
<br />
Metastases are responsible for the vast majority of cancer mortality, and brain metastases occur in 1/3 of adults suffering from cancer. Metastases to the brain are 10 times more frequent than primary brain tumors. The number of patients with brain metastases is increasing because treatments for primary cancers are continually improving, and patients are surviving with these diseases longer. The treatment of brain metastases is troublesome and inadequate due to limited effects of cytostatic medications and difficult compromises with respect to consequences of radiation and surgery on surrounding brain structures.<br />
<br />
Melanoma has the highest propensity to metastasize to the brain of all cancers. The median survival time with brain metastases is 6 months. The incidence of melanoma has increased over the last 3 decades, and the death rate continues to rise faster than the rate with most cancers. Recent results have shown that it is possible to develop genetically tailored therapy to various sub-populations of patients with metastatic melanoma ('''1-4''').<br />
<br />
Unfortunately, the mechanisms for metastatic spread of melanoma to the brain are largely unknown. This is due to the lack of relevant in vivo model systems. Patients with brain metastases are often excluded from larger clinical trials, leaving us uncertain about the effect of new therapeutic modalities. New research approaches and treatment strategies are clearly needed to improve the outcome for these patients.<br />
<br />
== Project overview ==<br />
<br />
We have developed competitive animal models to study cancer metastasis and especially to the brain. This project includes extensive use of advanced imaging technology (e.g. 7 Tesla MRI, PET and bioluminescence imaging), as well as state of the art genetic and proteomic analyses through close collaboration with national and international core facilities. Our model system has unique translational possibilities in characterizing cancer metastasis and developing new target specific treatment. Biological and therapeutical considerations have motivated us to study melanoma, but any cancer can in principle be studied. <br />
<br />
In our experimental model, cell lines from human melanoma brain metastases and cell lines from primary, cutaneous melanomas are injected into the left cardiac ventricle of immunodeficient mice. In our spontaneous model, the same cell lines are injected into the skin. We have been able to show that these cells form tumors in the mice, and that the metastatic cell populations more aggressively target the brain. Some of this work has already been published ('''5'''). Preliminary results were recently presented at the AACR in the USA, and as a consequence of this, we are now in the process of establishing a cooperation with the manufacturer of one of the most promising new drugs for metastatic melanoma (Vemurafenib/PLX4032; http://www.plexxikon.com) ('''3''').<br />
<br />
It has previously been shown that breast cancer cells prelabelled with micron-sized iron oxide particles (MPIOs) and thereafter injected intracardially into mice, can be tracked by MRI as single cells in the mouse brain ('''6'''). We are currently doing comprehensive MRI studies to elucidate the metastatic patterns and growth potentials of our cell lines by using a similar particle, called Fedex ('''7'''). This work is done in collaboration with Professor Arvid Lundervold at our department. We are able to visualize single cells labelled with Fedex in the animal brains, and through mathematical modelling we can quantify the brain cell load and follow the development of brain metastases, as well as the interesting aspects of tumor dormancy in the brain. This model system gives us a reliable tool, both quantitatively and qualitatively, to study the efficacy of new treatments.<br />
<br />
[[File:[[File:File.jpg]]]]<br />
<br />
We have developed cell lines from 7 human melanoma metastases. We are now working to characterize functional and structural differences in the metastatic patterns of cell lines derived from primary tumors and metastases (e.g. by 7 Tesla MRI, PET and bioluminescence imaging). This work will provides us with a groundwork for a more target specific identification and validation of genetic and epigenetic alterations responsible for melanoma disbursement and growth in the brain. Through functional assessments of candidate genes by overexpression and knockout studies, we hope to contribute to the development of more target specific and effective anti-tumor therapy. We are also in the process of investigating the significance of miRNAs in the metastatic process, by selective insertion of candidate miRNAs into the tumor cells.<br />
<br />
== References ==<br />
<br />
(1) Beadling et al. Clin Cancer Res 2008.<br />
(2) Carvajal et al. JAMA 2011.<br />
(3) Chapman et al. N Engl J Med 2011.<br />
(4) Flaherty et al. N Engl J Med 2010.<br />
(5) Wang et al. Neuropathol Appl Neurobiol 2011.<br />
(6) Bos et al. Nature 2009.<br />
(7) Babic et al. Bioconjug Chem 2008.</div>St03724https://wiki.app.uib.no/mriwiki/index.php?title=Terje_Sundstr%C3%B8m_PhD_project&diff=289Terje Sundstrøm PhD project2011-08-28T19:19:19Z<p>St03724: </p>
<hr />
<div>== '''Modeling melanoma brain metastasis: Towards more targeted treatment of cancer''' ==<br />
<br />
== Terje Sundstrøm ==<br />
<br />
Terje Sundstrøm is a MD from the University of Bergen in 2005, and a resident in neurosurgery at Haukeland University Hospital from 2007. As a medical student he started clinical research in neurosurgery. His efforts have so far generated 8 publications on different neurosurgical topics (http://www.uib.no/persons/Terje.Sundstrom). The applicant has during neurosurgical training been recruited to neuro-oncology and translational cancer research. Sundstrøm started his PhD project in January 2011 after receiving a 3-year scholarship from the Western Norway Regional Health Authority. His project on melanoma brain metastasis is a part of the Melanoma Metastasis Project headed by Professor Frits Thorsen, Translational Cancer Research Group, Department of Biomedicine, University of Bergen (http://www.uib.no/persons/Frits.Thorsen).<br />
<br />
== Project background ==<br />
<br />
Metastases are responsible for the vast majority of cancer mortality, and brain metastases occur in 1/3 of adults suffering from cancer. Metastases to the brain are 10 times more frequent than primary brain tumors. The number of patients with brain metastases is increasing because treatments for primary cancers are continually improving, and patients are surviving with these diseases longer. The treatment of brain metastases is troublesome and inadequate due to limited effects of cytostatic medications and difficult compromises with respect to consequences of radiation and surgery on surrounding brain structures.<br />
<br />
Melanoma has the highest propensity to metastasize to the brain of all cancers. The median survival time with brain metastases is 6 months. The incidence of melanoma has increased over the last 3 decades, and the death rate continues to rise faster than the rate with most cancers. Recent results have shown that it is possible to develop genetically tailored therapy to various sub-populations of patients with metastatic melanoma ('''1-4''').<br />
<br />
Unfortunately, the mechanisms for metastatic spread of melanoma to the brain are largely unknown. This is due to the lack of relevant in vivo model systems. Patients with brain metastases are often excluded from larger clinical trials, leaving us uncertain about the effect of new therapeutic modalities. New research approaches and treatment strategies are clearly needed to improve the outcome for these patients.<br />
<br />
== Project overview ==<br />
<br />
We have developed competitive animal models to study cancer metastasis and especially to the brain. This project includes extensive use of advanced imaging technology (e.g. 7 Tesla MRI, PET and bioluminescence imaging), as well as state of the art genetic and proteomic analyses through close collaboration with national and international core facilities. Our model system has unique translational possibilities in characterizing cancer metastasis and developing new target specific treatment. Biological and therapeutical considerations have motivated us to study melanoma, but any cancer can in principle be studied. <br />
<br />
In our experimental model, cell lines from human melanoma brain metastases and cell lines from primary, cutaneous melanomas are injected into the left cardiac ventricle of immunodeficient mice. In our spontaneous model, the same cell lines are injected into the skin. We have been able to show that these cells form tumors in the mice, and that the metastatic cell populations more aggressively target the brain. Some of this work has already been published ('''5'''). Preliminary results were recently presented at the AACR in the USA, and as a consequence of this, we are now in the process of establishing a cooperation with the manufacturer of one of the most promising new drugs for metastatic melanoma (Vemurafenib/PLX4032; http://www.plexxikon.com) ('''3''').<br />
<br />
It has previously been shown that breast cancer cells prelabelled with micron-sized iron oxide particles (MPIOs) and thereafter injected intracardially into mice, can be tracked by MRI as single cells in the mouse brain ('''6'''). We are currently doing comprehensive MRI studies to elucidate the metastatic patterns and growth potentials of our cell lines by using a similar particle, called Fedex7. This work is done in collaboration with Professor Arvid Lundervold at our department. We are able to visualize single cells labelled with Fedex in the animal brains, and through mathematical modelling we can quantify the brain cell load and follow the development of brain metastases, as well as the interesting aspects of tumor dormancy in the brain. This model system gives us a reliable tool, both quantitatively and qualitatively, to study the efficacy of new treatments.<br />
<br />
<br />
<br />
We have developed cell lines from 7 human melanoma metastases. We are now working to characterize functional and structural differences in the metastatic patterns of cell lines derived from primary tumors and metastases (e.g. by 7 Tesla MRI, PET and bioluminescence imaging). This work will provides us with a groundwork for a more target specific identification and validation of genetic and epigenetic alterations responsible for melanoma disbursement and growth in the brain. Through functional assessments of candidate genes by overexpression and knockout studies, we hope to contribute to the development of more target specific and effective anti-tumor therapy. We are also in the process of investigating the significance of miRNAs in the metastatic process, by selective insertion of candidate miRNAs into the tumor cells.<br />
<br />
== References ==<br />
<br />
(1) Beadling et al. Clin Cancer Res 2008.<br />
(2) Carvajal et al. JAMA 2011.<br />
(3) Chapman et al. N Engl J Med 2011.<br />
(4) Flaherty et al. N Engl J Med 2010.<br />
(5) Wang et al. Neuropathol Appl Neurobiol 2011.<br />
(6) Bos et al. Nature 2009.<br />
(7) Babic et al. Bioconjug Chem 2008.</div>St03724https://wiki.app.uib.no/mriwiki/index.php?title=Terje_Sundstr%C3%B8m_PhD_project&diff=288Terje Sundstrøm PhD project2011-08-28T19:18:26Z<p>St03724: </p>
<hr />
<div>== '''Modeling melanoma brain metastasis: Towards more targeted treatment of cancer''' ==<br />
<br />
== Terje Sundstrøm ==<br />
<br />
Terje Sundstrøm is a MD from the University of Bergen in 2005, and a resident in neurosurgery at Haukeland University Hospital from 2007. As a medical student he started clinical research in neurosurgery. His efforts have so far generated 8 publications on different neurosurgical topics (http://www.uib.no/persons/Terje.Sundstrom). The applicant has during neurosurgical training been recruited to neuro-oncology and translational cancer research. Sundstrøm started his PhD project in January 2011 after receiving a 3-year scholarship from the Western Norway Regional Health Authority. His project on melanoma brain metastasis is a part of the Melanoma Metastasis Project headed by Professor Frits Thorsen, Translational Cancer Research Group, Department of Biomedicine, University of Bergen (http://www.uib.no/persons/Frits.Thorsen).<br />
<br />
== Project background ==<br />
<br />
Metastases are responsible for the vast majority of cancer mortality, and brain metastases occur in 1/3 of adults suffering from cancer. Metastases to the brain are 10 times more frequent than primary brain tumors. The number of patients with brain metastases is increasing because treatments for primary cancers are continually improving, and patients are surviving with these diseases longer. The treatment of brain metastases is troublesome and inadequate due to limited effects of cytostatic medications and difficult compromises with respect to consequences of radiation and surgery on surrounding brain structures.<br />
<br />
Melanoma has the highest propensity to metastasize to the brain of all cancers. The median survival time with brain metastases is 6 months. The incidence of melanoma has increased over the last 3 decades, and the death rate continues to rise faster than the rate with most cancers. Recent results have shown that it is possible to develop genetically tailored therapy to various sub-populations of patients with metastatic melanoma ('''1-4''').<br />
<br />
Unfortunately, the mechanisms for metastatic spread of melanoma to the brain are largely unknown. This is due to the lack of relevant in vivo model systems. Patients with brain metastases are often excluded from larger clinical trials, leaving us uncertain about the effect of new therapeutic modalities. New research approaches and treatment strategies are clearly needed to improve the outcome for these patients.<br />
<br />
== Project overview ==<br />
<br />
We have developed competitive animal models to study cancer metastasis and especially to the brain. This project includes extensive use of advanced imaging technology (e.g. 7 Tesla MRI, PET and bioluminescence imaging), as well as state of the art genetic and proteomic analyses through close collaboration with national and international core facilities. Our model system has unique translational possibilities in characterizing cancer metastasis and developing new target specific treatment. Biological and therapeutical considerations have motivated us to study melanoma, but any cancer can in principle be studied. <br />
<br />
In our experimental model, cell lines from human melanoma brain metastases and cell lines from primary, cutaneous melanomas are injected into the left cardiac ventricle of immunodeficient mice. In our spontaneous model, the same cell lines are injected into the skin. We have been able to show that these cells form tumors in the mice, and that the metastatic cell populations more aggressively target the brain. Some of this work has already been published ('''5'''). Preliminary results were recently presented at the AACR in the USA, and as a consequence of this, we are now in the process of establishing a cooperation with the manufacturer of one of the most promising new drugs for metastatic melanoma (Vemurafenib/PLX4032; http://www.plexxikon.com) ('''3''').<br />
<br />
It has previously been shown that breast cancer cells prelabelled with micron-sized iron oxide particles (MPIOs) and thereafter injected intracardially into mice, can be tracked by MRI as single cells in the mouse brain ('''6'''). We are currently doing comprehensive MRI studies to elucidate the metastatic patterns and growth potentials of our cell lines by using a similar particle, called Fedex7. This work is done in collaboration with Professor Arvid Lundervold at our department. We are able to visualize single cells labelled with Fedex in the animal brains, and through mathematical modelling we can quantify the brain cell load and follow the development of brain metastases, as well as the interesting aspects of tumor dormancy in the brain. This model system gives us a reliable tool, both quantitatively and qualitatively, to study the efficacy of new treatments.<br />
<br />
== Figure ==<br />
<br />
<br />
We have developed cell lines from 7 human melanoma metastases. We are now working to characterize functional and structural differences in the metastatic patterns of cell lines derived from primary tumors and metastases (e.g. by 7 Tesla MRI, PET and bioluminescence imaging). This work will provides us with a groundwork for a more target specific identification and validation of genetic and epigenetic alterations responsible for melanoma disbursement and growth in the brain. Through functional assessments of candidate genes by overexpression and knockout studies, we hope to contribute to the development of more target specific and effective anti-tumor therapy. We are also in the process of investigating the significance of miRNAs in the metastatic process, by selective insertion of candidate miRNAs into the tumor cells.<br />
<br />
== References ==<br />
<br />
(1) Beadling et al. Clin Cancer Res 2008.<br />
(2) Carvajal et al. JAMA 2011.<br />
(3) Chapman et al. N Engl J Med 2011.<br />
(4) Flaherty et al. N Engl J Med 2010.<br />
(5) Wang et al. Neuropathol Appl Neurobiol 2011.<br />
(6) Bos et al. Nature 2009.<br />
(7) Babic et al. Bioconjug Chem 2008.</div>St03724https://wiki.app.uib.no/mriwiki/index.php?title=File:Figure_1.jpg&diff=287File:Figure 1.jpg2011-08-28T19:15:26Z<p>St03724: Figure 1</p>
<hr />
<div>Figure 1</div>St03724https://wiki.app.uib.no/mriwiki/index.php?title=Terje_Sundstr%C3%B8m_PhD_project&diff=286Terje Sundstrøm PhD project2011-08-28T19:11:22Z<p>St03724: </p>
<hr />
<div>== '''Modeling melanoma brain metastasis: Towards more targeted treatment of cancer''' ==<br />
<br />
== Terje Sundstrøm ==<br />
<br />
Terje Sundstrøm is a MD from the University of Bergen in 2005, and a resident in neurosurgery at Haukeland University Hospital from 2007. As a medical student he started clinical research in neurosurgery. His efforts have so far generated 8 publications on different neurosurgical topics (http://www.uib.no/persons/Terje.Sundstrom). The applicant has during neurosurgical training been recruited to neuro-oncology and translational cancer research. Sundstrøm started his PhD project in January 2011 after receiving a 3-year scholarship from the Western Norway Regional Health Authority. His project on melanoma brain metastasis is a part of the Melanoma Metastasis Project headed by Professor Frits Thorsen, Translational Cancer Research Group, Department of Biomedicine, University of Bergen (http://www.uib.no/persons/Frits.Thorsen).<br />
<br />
== Project background ==<br />
<br />
Metastases are responsible for the vast majority of cancer mortality, and brain metastases occur in 1/3 of adults suffering from cancer. Metastases to the brain are 10 times more frequent than primary brain tumors. The number of patients with brain metastases is increasing because treatments for primary cancers are continually improving, and patients are surviving with these diseases longer. The treatment of brain metastases is troublesome and inadequate due to limited effects of cytostatic medications and difficult compromises with respect to consequences of radiation and surgery on surrounding brain structures.<br />
<br />
Melanoma has the highest propensity to metastasize to the brain of all cancers. The median survival time with brain metastases is 6 months. The incidence of melanoma has increased over the last 3 decades, and the death rate continues to rise faster than the rate with most cancers. Recent results have shown that it is possible to develop genetically tailored therapy to various sub-populations of patients with metastatic melanoma ('''1-4''').<br />
<br />
Unfortunately, the mechanisms for metastatic spread of melanoma to the brain are largely unknown. This is due to the lack of relevant in vivo model systems. Patients with brain metastases are often excluded from larger clinical trials, leaving us uncertain about the effect of new therapeutic modalities. New research approaches and treatment strategies are clearly needed to improve the outcome for these patients.<br />
<br />
== Project overview ==<br />
<br />
We have developed competitive animal models to study cancer metastasis and especially to the brain. This project includes extensive use of advanced imaging technology (e.g. 7 Tesla MRI, PET and bioluminescence imaging), as well as state of the art genetic and proteomic analyses through close collaboration with national and international core facilities. Our model system has unique translational possibilities in characterizing cancer metastasis and developing new target specific treatment. Biological and therapeutical considerations have motivated us to study melanoma, but any cancer can in principle be studied. <br />
<br />
In our experimental model, cell lines from human melanoma brain metastases and cell lines from primary, cutaneous melanomas are injected into the left cardiac ventricle of immunodeficient mice. In our spontaneous model, the same cell lines are injected into the skin. We have been able to show that these cells form tumors in the mice, and that the metastatic cell populations more aggressively target the brain. Some of this work has already been published ('''5'''). Preliminary results were recently presented at the AACR in the USA, and as a consequence of this, we are now in the process of establishing a cooperation with the manufacturer of one of the most promising new drugs for metastatic melanoma (Vemurafenib/PLX4032; http://www.plexxikon.com) ('''3''').<br />
<br />
It has previously been shown that breast cancer cells prelabelled with micron-sized iron oxide particles (MPIOs) and thereafter injected intracardially into mice, can be tracked by MRI as single cells in the mouse brain ('''6'''). We are currently doing comprehensive MRI studies to elucidate the metastatic patterns and growth potentials of our cell lines by using a similar particle, called Fedex7. This work is done in collaboration with Professor Arvid Lundervold at our department. We are able to visualize single cells labelled with Fedex in the animal brains, and through mathematical modelling we can quantify the brain cell load and follow the development of brain metastases, as well as the interesting aspects of tumor dormancy in the brain. This model system gives us a reliable tool, both quantitatively and qualitatively, to study the efficacy of new treatments.<br />
<br />
[[File:File.jpg]]<br />
<br />
We have developed cell lines from 7 human melanoma metastases. We are now working to characterize functional and structural differences in the metastatic patterns of cell lines derived from primary tumors and metastases (e.g. by 7 Tesla MRI, PET and bioluminescence imaging). This work will provides us with a groundwork for a more target specific identification and validation of genetic and epigenetic alterations responsible for melanoma disbursement and growth in the brain. Through functional assessments of candidate genes by overexpression and knockout studies, we hope to contribute to the development of more target specific and effective anti-tumor therapy. We are also in the process of investigating the significance of miRNAs in the metastatic process, by selective insertion of candidate miRNAs into the tumor cells.<br />
<br />
== References ==<br />
<br />
(1) Beadling et al. Clin Cancer Res 2008.<br />
(2) Carvajal et al. JAMA 2011.<br />
(3) Chapman et al. N Engl J Med 2011.<br />
(4) Flaherty et al. N Engl J Med 2010.<br />
(5) Wang et al. Neuropathol Appl Neurobiol 2011.<br />
(6) Bos et al. Nature 2009.<br />
(7) Babic et al. Bioconjug Chem 2008.</div>St03724https://wiki.app.uib.no/mriwiki/index.php?title=Terje_Sundstr%C3%B8m_PhD_project&diff=285Terje Sundstrøm PhD project2011-08-28T19:09:02Z<p>St03724: </p>
<hr />
<div><br />
== '''Modeling melanoma brain metastasis: Towards more targeted treatment of cancer''' ==<br />
<br />
== Terje Sundstrøm ==<br />
<br />
Terje Sundstrøm is a MD from the University of Bergen in 2005, and a resident in neurosurgery at Haukeland University Hospital from 2007. As a medical student he started clinical research in neurosurgery. His efforts have so far generated 8 publications on different neurosurgical topics (http://www.uib.no/persons/Terje.Sundstrom). The applicant has during neurosurgical training been recruited to neuro-oncology and translational cancer research. Sundstrøm started his PhD project in January 2011 after receiving a 3-year scholarship from the Western Norway Regional Health Authority. His project on melanoma brain metastasis is a part of the Melanoma Metastasis Project headed by Professor Frits Thorsen, Translational Cancer Research Group, Department of Biomedicine, University of Bergen (http://www.uib.no/persons/Frits.Thorsen).<br />
<br />
== Project background ==<br />
<br />
Metastases are responsible for the vast majority of cancer mortality, and brain metastases occur in 1/3 of adults suffering from cancer. Metastases to the brain are 10 times more frequent than primary brain tumors. The number of patients with brain metastases is increasing because treatments for primary cancers are continually improving, and patients are surviving with these diseases longer. The treatment of brain metastases is troublesome and inadequate due to limited effects of cytostatic medications and difficult compromises with respect to consequences of radiation and surgery on surrounding brain structures.<br />
<br />
Melanoma has the highest propensity to metastasize to the brain of all cancers. The median survival time with brain metastases is 6 months. The incidence of melanoma has increased over the last 3 decades, and the death rate continues to rise faster than the rate with most cancers. Recent results have shown that it is possible to develop genetically tailored therapy to various sub-populations of patients with metastatic melanoma1-4.<br />
<br />
Unfortunately, the mechanisms for metastatic spread of melanoma to the brain are largely unknown. This is due to the lack of relevant in vivo model systems. Patients with brain metastases are often excluded from larger clinical trials, leaving us uncertain about the effect of new therapeutic modalities. New research approaches and treatment strategies are clearly needed to improve the outcome for these patients.<br />
<br />
== Project overview ==<br />
<br />
We have developed competitive animal models to study cancer metastasis and especially to the brain. This project includes extensive use of advanced imaging technology (e.g. 7 Tesla MRI, PET and bioluminescence imaging), as well as state of the art genetic and proteomic analyses through close collaboration with national and international core facilities. Our model system has unique translational possibilities in characterizing cancer metastasis and developing new target specific treatment. Biological and therapeutical considerations have motivated us to study melanoma, but any cancer can in principle be studied. <br />
<br />
In our experimental model, cell lines from human melanoma brain metastases and cell lines from primary, cutaneous melanomas are injected into the left cardiac ventricle of immunodeficient mice. In our spontaneous model, the same cell lines are injected into the skin. We have been able to show that these cells form tumors in the mice, and that the metastatic cell populations more aggressively target the brain. Some of this work has already been published5. Preliminary results were recently presented at the AACR in the USA, and as a consequence of this, we are now in the process of establishing a cooperation with the manufacturer of one of the most promising new drugs for metastatic melanoma (Vemurafenib/PLX4032; http://www.plexxikon.com)3.<br />
<br />
It has previously been shown that breast cancer cells prelabelled with micron-sized iron oxide particles (MPIOs) and thereafter injected intracardially into mice, can be tracked by MRI as single cells in the mouse brain6. We are currently doing comprehensive MRI studies to elucidate the metastatic patterns and growth potentials of our cell lines by using a similar particle, called Fedex7. This work is done in collaboration with Professor Arvid Lundervold at our department. We are able to visualize single cells labelled with Fedex in the animal brains, and through mathematical modelling we can quantify the brain cell load and follow the development of brain metastases, as well as the interesting aspects of tumor dormancy in the brain. This model system gives us a reliable tool, both quantitatively and qualitatively, to study the efficacy of new treatments.<br />
<br />
[[File:File.jpg]]<br />
<br />
We have developed cell lines from 7 human melanoma metastases. We are now working to characterize functional and structural differences in the metastatic patterns of cell lines derived from primary tumors and metastases (e.g. by 7 Tesla MRI, PET and bioluminescence imaging). This work will provides us with a groundwork for a more target specific identification and validation of genetic and epigenetic alterations responsible for melanoma disbursement and growth in the brain. Through functional assessments of candidate genes by overexpression and knockout studies, we hope to contribute to the development of more target specific and effective anti-tumor therapy. We are also in the process of investigating the significance of miRNAs in the metastatic process, by selective insertion of candidate miRNAs into the tumor cells.<br />
<br />
== References ==<br />
<br />
(1) Beadling et al. Clin Cancer Res 2008.<br />
(2) Carvajal et al. JAMA 2011.<br />
(3) Chapman et al. N Engl J Med 2011.<br />
(4) Flaherty et al. N Engl J Med 2010.<br />
(5) Wang et al. Neuropathol Appl Neurobiol 2011.<br />
(6) Bos et al. Nature 2009.<br />
(7) Babic et al. Bioconjug Chem 2008.</div>St03724https://wiki.app.uib.no/mriwiki/index.php?title=Terje_Sundstr%C3%B8m_PhD_project&diff=284Terje Sundstrøm PhD project2011-08-28T19:07:35Z<p>St03724: </p>
<hr />
<div>'''Modeling melanoma brain metastasis: Towards more targeted treatment of cancer'''<br />
<br />
<br />
== Terje Sundstrøm ==<br />
<br />
Terje Sundstrøm is a MD from the University of Bergen in 2005, and a resident in neurosurgery at Haukeland University Hospital from 2007. As a medical student he started clinical research in neurosurgery. His efforts have so far generated 8 publications on different neurosurgical topics (http://www.uib.no/persons/Terje.Sundstrom). The applicant has during neurosurgical training been recruited to neuro-oncology and translational cancer research. Sundstrøm started his PhD project in January 2011 after receiving a 3-year scholarship from the Western Norway Regional Health Authority. His project on melanoma brain metastasis is a part of the Melanoma Metastasis Project headed by Professor Frits Thorsen, Translational Cancer Research Group, Department of Biomedicine, University of Bergen (http://www.uib.no/persons/Frits.Thorsen).<br />
<br />
<br />
== Project background ==<br />
<br />
Metastases are responsible for the vast majority of cancer mortality, and brain metastases occur in 1/3 of adults suffering from cancer. Metastases to the brain are 10 times more frequent than primary brain tumors. The number of patients with brain metastases is increasing because treatments for primary cancers are continually improving, and patients are surviving with these diseases longer. The treatment of brain metastases is troublesome and inadequate due to limited effects of cytostatic medications and difficult compromises with respect to consequences of radiation and surgery on surrounding brain structures.<br />
<br />
Melanoma has the highest propensity to metastasize to the brain of all cancers. The median survival time with brain metastases is 6 months. The incidence of melanoma has increased over the last 3 decades, and the death rate continues to rise faster than the rate with most cancers. Recent results have shown that it is possible to develop genetically tailored therapy to various sub-populations of patients with metastatic melanoma1-4.<br />
<br />
Unfortunately, the mechanisms for metastatic spread of melanoma to the brain are largely unknown. This is due to the lack of relevant in vivo model systems. Patients with brain metastases are often excluded from larger clinical trials, leaving us uncertain about the effect of new therapeutic modalities. New research approaches and treatment strategies are clearly needed to improve the outcome for these patients.<br />
<br />
<br />
== Project overview ==<br />
<br />
We have developed competitive animal models to study cancer metastasis and especially to the brain. This project includes extensive use of advanced imaging technology (e.g. 7 Tesla MRI, PET and bioluminescence imaging), as well as state of the art genetic and proteomic analyses through close collaboration with national and international core facilities. Our model system has unique translational possibilities in characterizing cancer metastasis and developing new target specific treatment. Biological and therapeutical considerations have motivated us to study melanoma, but any cancer can in principle be studied. <br />
<br />
In our experimental model, cell lines from human melanoma brain metastases and cell lines from primary, cutaneous melanomas are injected into the left cardiac ventricle of immunodeficient mice. In our spontaneous model, the same cell lines are injected into the skin. We have been able to show that these cells form tumors in the mice, and that the metastatic cell populations more aggressively target the brain. Some of this work has already been published5. Preliminary results were recently presented at the AACR in the USA, and as a consequence of this, we are now in the process of establishing a cooperation with the manufacturer of one of the most promising new drugs for metastatic melanoma (Vemurafenib/PLX4032; http://www.plexxikon.com)3.<br />
<br />
It has previously been shown that breast cancer cells prelabelled with micron-sized iron oxide particles (MPIOs) and thereafter injected intracardially into mice, can be tracked by MRI as single cells in the mouse brain6. We are currently doing comprehensive MRI studies to elucidate the metastatic patterns and growth potentials of our cell lines by using a similar particle, called Fedex7. This work is done in collaboration with Professor Arvid Lundervold at our department. We are able to visualize single cells labelled with Fedex in the animal brains, and through mathematical modelling we can quantify the brain cell load and follow the development of brain metastases, as well as the interesting aspects of tumor dormancy in the brain. This model system gives us a reliable tool, both quantitatively and qualitatively, to study the efficacy of new treatments.<br />
<br />
[[File:File.jpg]]<br />
<br />
We have developed cell lines from 7 human melanoma metastases. We are now working to characterize functional and structural differences in the metastatic patterns of cell lines derived from primary tumors and metastases (e.g. by 7 Tesla MRI, PET and bioluminescence imaging). This work will provides us with a groundwork for a more target specific identification and validation of genetic and epigenetic alterations responsible for melanoma disbursement and growth in the brain. Through functional assessments of candidate genes by overexpression and knockout studies, we hope to contribute to the development of more target specific and effective anti-tumor therapy. We are also in the process of investigating the significance of miRNAs in the metastatic process, by selective insertion of candidate miRNAs into the tumor cells.<br />
<br />
References<br />
(1) Beadling et al. Clin Cancer Res 2008.<br />
(2) Carvajal et al. JAMA 2011.<br />
(3) Chapman et al. N Engl J Med 2011.<br />
(4) Flaherty et al. N Engl J Med 2010.<br />
(5) Wang et al. Neuropathol Appl Neurobiol 2011.<br />
(6) Bos et al. Nature 2009.<br />
(7) Babic et al. Bioconjug Chem 2008.</div>St03724https://wiki.app.uib.no/mriwiki/index.php?title=Terje_Sundstr%C3%B8m_PhD_project&diff=283Terje Sundstrøm PhD project2011-08-28T19:03:05Z<p>St03724: Created page with 'Modeling melanoma brain metastasis: Towards more targeted treatment of cancer Applicant Terje Sundstrøm is a MD from the University of Bergen in 2005, and a resident in neurosu…'</p>
<hr />
<div>Modeling melanoma brain metastasis: Towards more targeted treatment of cancer<br />
<br />
Applicant<br />
Terje Sundstrøm is a MD from the University of Bergen in 2005, and a resident in neurosurgery at Haukeland University Hospital from 2007. As a medical student he started clinical research in neurosurgery. His efforts have so far generated 8 publications on different neurosurgical topics (http://www.uib.no/persons/Terje.Sundstrom). The applicant has during neurosurgical training been recruited to neuro-oncology and translational cancer research. Sundstrøm started his PhD project in January 2011 after receiving a 3-year scholarship from the Western Norway Regional Health Authority. His project on melanoma brain metastasis is a part of the Melanoma Metastasis Project headed by Professor Frits Thorsen, Translational Cancer Research Group, Department of Biomedicine, University of Bergen (http://www.uib.no/persons/Frits.Thorsen).<br />
<br />
Background<br />
Metastases are responsible for the vast majority of cancer mortality, and brain metastases occur in 1/3 of adults suffering from cancer. Metastases to the brain are 10 times more frequent than primary brain tumors. The number of patients with brain metastases is increasing because treatments for primary cancers are continually improving, and patients are surviving with these diseases longer. The treatment of brain metastases is troublesome and inadequate due to limited effects of cytostatic medications and difficult compromises with respect to consequences of radiation and surgery on surrounding brain structures.<br />
<br />
Melanoma has the highest propensity to metastasize to the brain of all cancers. The median survival time with brain metastases is 6 months. The incidence of melanoma has increased over the last 3 decades, and the death rate continues to rise faster than the rate with most cancers. Recent results have shown that it is possible to develop genetically tailored therapy to various sub-populations of patients with metastatic melanoma1-4.<br />
<br />
Unfortunately, the mechanisms for metastatic spread of melanoma to the brain are largely unknown. This is due to the lack of relevant in vivo model systems. Patients with brain metastases are often excluded from larger clinical trials, leaving us uncertain about the effect of new therapeutic modalities. New research approaches and treatment strategies are clearly needed to improve the outcome for these patients.<br />
<br />
Overview<br />
We have developed competitive animal models to study cancer metastasis and especially to the brain. This project includes extensive use of advanced imaging technology (e.g. 7 Tesla MRI, PET and bioluminescence imaging), as well as state of the art genetic and proteomic analyses through close collaboration with national and international core facilities. Our model system has unique translational possibilities in characterizing cancer metastasis and developing new target specific treatment. Biological and therapeutical considerations have motivated us to study melanoma, but any cancer can in principle be studied. <br />
<br />
In our experimental model, cell lines from human melanoma brain metastases and cell lines from primary, cutaneous melanomas are injected into the left cardiac ventricle of immunodeficient mice. In our spontaneous model, the same cell lines are injected into the skin. We have been able to show that these cells form tumors in the mice, and that the metastatic cell populations more aggressively target the brain. Some of this work has already been published5. Preliminary results were recently presented at the AACR in the USA, and as a consequence of this, we are now in the process of establishing a cooperation with the manufacturer of one of the most promising new drugs for metastatic melanoma (Vemurafenib/PLX4032; http://www.plexxikon.com)3.<br />
<br />
It has previously been shown that breast cancer cells prelabelled with micron-sized iron oxide particles (MPIOs) and thereafter injected intracardially into mice, can be tracked by MRI as single cells in the mouse brain6. We are currently doing comprehensive MRI studies to elucidate the metastatic patterns and growth potentials of our cell lines by using a similar particle, called Fedex7. This work is done in collaboration with Professor Arvid Lundervold at our department. We are able to visualize single cells labelled with Fedex in the animal brains, and through mathematical modelling we can quantify the brain cell load and follow the development of brain metastases, as well as the interesting aspects of tumor dormancy in the brain. This model system gives us a reliable tool, both quantitatively and qualitatively, to study the efficacy of new treatments.<br />
<br />
[[File:File.jpg]]<br />
<br />
We have developed cell lines from 7 human melanoma metastases. We are now working to characterize functional and structural differences in the metastatic patterns of cell lines derived from primary tumors and metastases (e.g. by 7 Tesla MRI, PET and bioluminescence imaging). This work will provides us with a groundwork for a more target specific identification and validation of genetic and epigenetic alterations responsible for melanoma disbursement and growth in the brain. Through functional assessments of candidate genes by overexpression and knockout studies, we hope to contribute to the development of more target specific and effective anti-tumor therapy. We are also in the process of investigating the significance of miRNAs in the metastatic process, by selective insertion of candidate miRNAs into the tumor cells.</div>St03724