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Publication : Genetic analysis of chemoresistance in primary murine lymphomas.

First Author  Schmitt CA Year  2000
Journal  Nat Med Volume  6
Issue  9 Pages  1029-35
PubMed ID  10973324 Mgi Jnum  J:64496
Mgi Id  MGI:1889417 Doi  10.1038/79542
Citation  Schmitt CA, et al. (2000) Genetic analysis of chemoresistance in primary murine lymphomas. Nat Med 6(9):1029-35
abstractText  Understanding the basis of chemoresistance is a principal goal of molecular oncology. We have exploited a murine lymphoma model and retroviral gene transfer to rapidly generate a series of spontaneous tumors differing only in a gene of interest, and subsequently studied the impact of the test gene on the treatment sensitivity of tumors at their natural site. We demonstrate that the Bcl-2 oncoprotein produces multi-drug resistance when assessed in primary lymphomas in vivo. In contrast, this effect was dramatically reduced when the primary lymphomas were subjected to long-term culture, and completely missed in the standard clonogenic survival assay. This model highlights the importance of physiological test systems to address the complexity of clinical drug resistance and provides a novel strategy to evaluate compounds targeting specific genetic lesions.
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