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Cancers 2019, 11(2), 242; https://doi.org/10.3390/cancers11020242

Mouse-Derived Isograft (MDI) In Vivo Tumor Models II. Carcinogen-Induced cMDI Models: Characterization and Cancer Therapeutic Approaches

1
In Vivo Pharmacology, ProQinase GmbH, Breisacher Str. 117, 79106 Freiburg, Germany
2
TPL Pathology Labs, Sasbacher Str. 10, 79111 Freiburg, Germany
*
Authors to whom correspondence should be addressed.
Current address: Charles River Discovery Research Services Germany GmbH, Am Flughafen 12-14, 79108 Freiburg, Germany.
These authors contributed equally to this work.
Received: 1 December 2018 / Revised: 8 February 2019 / Accepted: 13 February 2019 / Published: 19 February 2019
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Abstract

In this second study, we established syngeneic in vivo models named carcinogen-induced mouse-derived isografts (cMDIs). Carcinogen-induced tumors were obtained during short-term observation (3–9 months) of CBA/J mice treated with various administration routes with 3-methylcholanthrene (MCA) or N-methyl-N-nitrosourea (MNU) as carcinogens. During necropsy, primary tumors and suspicious tissues were assessed macroscopically and re-transplanted (in PDX-like manner) into sex-matched syngeneic animals. Outgrowing tumors were histologically characterized as either spinocellular carcinoma (1/8) or various differentiated sarcomas (7/8). Growth curves of four sarcomas showed striking heterogeneity. These cMDIs were further characterized by flow cytometry, RNA sequencing, or efficacy studies. A variable invasion of immune cells into the tumors, as well as varying expression of tyrosine kinase receptor, IFN-γ signature, or immune cell population marker genes could be observed. Immune checkpoint inhibitor treatment (anti-mPD-1, anti-mCTLA-4, or a combination thereof) showed different responses in the various cMDI models. In general, cMDI models are carcinogen-induced tumors of low passage number that were propagated as tissue pieces in mice without any tissue culturing. Therefore, the tumors contained conserved tumor characteristics and intratumoral immune cell populations. In contrast to the previously described spontaneous MDI, carcinogen induction resulted in a greater number of individual but histologically related tumors, which were preferentially sarcomas. View Full-Text
Keywords: mouse tumor models; experimental cancer; mouse-derived isografts (MDIs); carcinogen-induced tumors; therapy; immune checkpoint inhibitors; immunocompetent animals; syngeneic mouse tumor models; experimental cancer; mouse-derived isografts (MDIs); carcinogen-induced tumors; therapy; immune checkpoint inhibitors; immunocompetent animals; syngeneic
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Beshay, J.; Jantscheff, P.; Lemarchand, T.; Obodozie, C.; Schächtele, C.; Weber, H. Mouse-Derived Isograft (MDI) In Vivo Tumor Models II. Carcinogen-Induced cMDI Models: Characterization and Cancer Therapeutic Approaches. Cancers 2019, 11, 242.

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