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Patient derived tumor xenografts (PDTX) are created when cancerous tissue from a patient’s primary tumor is implanted directly into an immunodeficient mouse. PDTX models are providing solutions to the challenges that researchers face in cancer drug research such as positive tumor responses in mouse models but not translating over when the study is implemented in humans. As a result, PDTX cancer models are becoming popular models to use in cancer drug research. ==Methods of tumor xenotransplantation== Several types of immunodeficient mice can be used to establish PDTX models: athymic nude mice, severe combined immune deficient (SCID) mice, nonobese diabetic (NOD)-SCID mice, and recombination-activating gene 2 (Rag2)-knockout mice. The mice used must be immunocompromised to prevent transplant rejection. The NOD-SCID mouse is considered more immunodeficient than the nude mouse, and therefore is more commonly used for PDTX models because the NOD-SCID mouse does not produce Natural Killer cells. When human tumors are resected, necrotic tissues is removed and the tumor is either mechanically sectioned into smaller fragments or chemically digested or physically manipulated into a single-cell suspension. There are both advantages and disadvantages in utilizing either discrete tumor fragments or single-cell suspensions. Tumor fragments retain cell-cell interactions as well as some tissue architecture of the original tumor, therefore mimicking the tumor microenvironment. Alternatively, single-cell suspension enables scientists to collect an unbiased sampling of the whole tumor, eliminating spatially segregate subclones that are otherwise inadvertently selected during analysis or tumor passaging〔 However, single-cell suspensions subject surviving cells to harsh chemical or mechanical forces that may sensitize cells to anoikis, taking a toll on cell viability and engraftment success. Unlike creating xenograft mouse models using existing cancer cell lines, there are no intermediate ''in vitro'' processing steps before implanting tumor fragments murine host to create a PDTX. The tumor fragments are either be implanted heterotopically or orthotopically of an immunodeficient mouse. Heterotopical implants occur when the tumor fragment is implanted into an area of the mouse unrelated to the original tumor site, generally subcutaneously or subrenal capsular sites. Whereas, scientists tranplant the patient’s tumor tissue and implants the fragments into the corresponding anatomical position in the mouse in an orthotopic transplant. Subcutaneous PDTX rarely produce metastasis in mice, does not simulate the initial tumor microenvironment, and has engraftment rates 40-60%.〔 Subrenal capsular PDTX maintains the original tumor stroma as well as the equivalent host stroma and has an engraftment rate of 95%. Ultimately, the time it takes about 2 to 4 months for the tumor to engraft varying by tumor type, implant location, and strain of immunodeficient mice utilized; engraftment failure should not be declared until at least 6 months.〔 The first generation of mice receiving the patient's tumor fragments are commonly denoted F0. When the tumor-burden becomes too large for the F0 mouse, researchers passage the tumor over to the next generation of mice. Each generation thereafter is denoted F1, F2, F3…Fn. For drug development studies, expansion of mice after the F3 generation is often utilized after ensuring that the PDTX has not genetically or histologically diverged from the patient’s tumor.〔 ''Note: open access via PMC; closed via publisher site.''〕 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Patient derived tumor xenografts」の詳細全文を読む スポンサード リンク
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