We examined whether transplantation of bone marrow-derived stromal cells

They demonstrated greater tumor growth in the athymic mice as compared to control, leading to the use of immunodeficient mice becoming common practice for PDX development. Recently, PDXs have been generated for a number of cancers including pancreatic, breast, lung, renal and head and neck. These studies showed that PDXs retain characteristics of the primary tumor across serial passages both at the histologic and molecular levels. Daniel et al. also demonstrated that their primary small cell lung cancer PDX retained greater similarity to the patient��s tumor as compared to a cell line generated from the same PDX. Moreover, our group and others have successfully cryopreserved and reanimated PDXs at a later time, increasing the utility of this model system. Thus, PDXs represent a validated and reliable model for studying a variety of human cancers. A powerful use for PDXs is the TC-I 2000 testing of standard and novel treatments in an in vivo system with greater heterogeneity than genetically engineered mouse models and a more relevant tumor microenvironment than cell lines. Once established, PDXs are amplified in vivo, injected into numerous mice, and the mice are subsequently stratified into different treatment groups. The capacity of a specific treatment regimen to slow or halt tumor growth can be assessed by comparing the mean tumor growth over time for each group as compared to control mice. In this manner, Raclopride investigators can evaluate the effect of many alternate therapies on one specific tumor type derived from a single patient. Additionally, molecular alterations induced by the different treatments can be analyzed by harvesting post-treatment tumor samples either by flash freezing tumor chunks in liquid nitrogen for genome wide studies or fixing tumors in formalin followed by paraffin embedding for biomarker analysis. It has also been argued that this model system could be employed in personalized cancer therapy by generating PDXs from a patient��s cancer, testing a variety of chemotherapeutics on mice bearing their tumor and then selecting a new treatment regimen for the patient based on these in vivo results. There are a number of variations in the procedures used to establish PDXs. For example, some groups describe surgical implantation of small tumor chunks into the flanks while others mince the tumors to create a cell suspension and inject the suspension subcutaneously through a large gauge needle.

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