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Thursday, September 15, 2016 6:45 AM|Li, P., Lee, E. H., Du, F., Gordon, R. E., Yuelling, L. W., Liu, Y., Ng, J. M. Y., Zhang, H., Wu, J., Korshunov, A., Pfister, S. M., Curran, T., Yang, Z.-j.|Cancer Research current issue|Labels: Hh/SMO, medulloblastoma
The intermediate filament protein Nestin serves as a biomarker for stem cells and has been used to identify subsets of cancer stem–like cells. However, the mechanistic contributions of Nestin to cancer pathogenesis are not understood. Here, we report that Nestin binds the hedgehog pathway transcription factor Gli3 to mediate the development of medulloblastomas of the hedgehog subtype. In a mouse model system, Nestin levels increased progressively during medulloblastoma formation, resulting in enhanced tumor growth. Conversely, loss of Nestin dramatically inhibited proliferation and promoted differentiation. Mechanistic investigations revealed that the tumor-promoting effects of Nestin were mediated by binding to Gli3, a zinc finger transcription factor that negatively regulates hedgehog signaling. Nestin binding to Gli3 blocked Gli3 phosphorylation and its subsequent proteolytic processing, thereby abrogating its ability to negatively regulate the hedgehog pathway. Our findings show how Nestin drives hedgehog pathway–driven cancers and uncover in Gli3 a therapeutic target to treat these malignancies. Cancer Res; 76(18); 5573–83. ©2016 AACR.
Wednesday, September 14, 2016 4:21 PM|Fred Hutchinson Cancer Research Center/UW Medicine Cancer Consortium - Clinical Trials|Labels: brain cancer, clinical trial, medulloblastoma
This randomized phase III trial studies different chemotherapy and radiation therapy regimens to compare how well they work in treating young patients with newly diagnosed, previously untreated, high-risk medulloblastoma. Drugs used in chemotherapy, such as vincristine sulfate, cisplatin, cyclophosphamide, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Isotretinoin may help chemotherapy work better by making tumor cells more sensitive to the drugs. Radiation therapy uses high-energy x-rays to kill tumor cells. Carboplatin may make tumor cells more sensitive to radiation therapy. It is not yet known which chemotherapy and radiation therapy regimen is more effective in treating brain tumors.
Wednesday, September 14, 2016 4:21 PM|Fred Hutchinson Cancer Research Center/UW Medicine Cancer Consortium - Clinical Trials|Labels: brain cancer, childhood cancer, clinical trial, medulloblastoma
This phase II trial studies how well combination chemotherapy works in treating younger patients with newly diagnosed, non-metastatic desmoplastic medulloblastoma. Drugs used in chemotherapy, such as vincristine sulfate, cyclophosphamide, methotrexate, etoposide, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.
Wednesday, August 31, 2016 10:05 PM|Unknown Author|Cancer Discovery current issue|Labels: CDK, PD-1/PD-L1, brain cancer, medulloblastoma

CDK5 suppression promotes CD4+ T cell–mediated antitumor immunity in medulloblastoma.

Tuesday, August 16, 2016 7:27 AM|Onclive Brain Cancer Articles|Labels: brain cancer, medulloblastoma
To discover targeted therapies for the more common and severe types of medulloblastoma, a laboratory at Sanford Burnham Prebys Medical Discovery Institute has led efforts to develop genetically engineered mouse models and patient-derived xenografts for studying the molecular basis of the disease.
Tuesday, January 12, 2016 4:00 PM|Nature|MedWorm: Cancer Therapy|Comments|Labels: brain cancer, medulloblastoma
Authors: A. Sorana Morrissy, Livia Garzia, David J. H. Shih, Scott Zuyderduyn, Xi Huang, Patryk Skowron, Marc Remke, Florence M. G. Cavalli, Vijay Ramaswamy, Patricia E. Lindsay, Salomeh Jelveh, Laura K. Donovan, Xin Wang, Betty Luu, Kory Zayne, Yisu Li, Chelsea Mayoh, Nina Thiessen, Eloi Mercier, Karen L. Mungall, Yusanne Ma, Kane Tse, Thomas Zeng, Karey Shumansky, Andrew J. L. Roth, Sohrab Shah, Hamza Farooq, Noriyuki Kijima, Borja L. Holgado, John J. Y. Lee, Stuart Matan-Lithwick, Jessica Liu, Stephen C. Mack, Alex Manno, K. A. Michealraj, Carolina Nor, John Peacock, Lei Qin, Juri Reimand, Adi Rolider, Yuan Y. Thompson, Xiaochong Wu, Trevor Pugh, Adrian Ally, Mikhail Bilenky, Yaron S. N. Butterfield, Rebecca Carlsen, Young Cheng, Eric Chuah, Richard D. Corbett, Noreen Dhalla, An He, Dar...