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The XactMice: A Xenochimaeric Mouse with Tumor and Hematopoietic System Obtained from the Same Patient

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Annual rept. 15 Sep 2010-14 Sep 2011

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The lack of faithful animal models limits cancer research. One of the major factors is that regular animal models are a mixture of human tumor cells supported by mouse stroma cells, and this can have a major negative impact in research, particularly that aiming at unraveling the genetic basis of cancer as this disrupts gene expression, and cancer stem cell and stroma studies. Aims Generate a fully humanized and individualized model XactMice by acquiring and engrafting paired tumor and immortalized bone marrow precursors from the same patient in an immune-deficient mouse model. Our second Aim is to demonstrate the stability and authenticity of XactMice by comparing its gene expression, cancer stem cell profile, and drug sensitivity with a regular xenograft, and the patients gene profile and outcome. Results In the first year of funding we have 1 improved the methods for stabilized bone marrow precursor generation, enabling the use of lower amounts of initial patient cells 2 demonstrated human tumors grow on a humanized mouse model 3 shown that human stroma homes in to the tumor by dual DNA analyses and 4 initiated patient material collection and processing. Impact on Cancer Research Patients This project could result in establishing a seemingly ideal model for cancer research, with especial potential to unravel the interactions between tumor and stroma. The potential repercussions in our understanding of processes like angiogenesis and metastasis are profound. This work has the potential to yield high impact data and open new avenues of investigation into mechanisms and targeting of tumor dormancy.

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  • Medicine and Medical Research

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