A series of lupane-, oleanane-and dammarane-based triterpenoids with 3β-amino, A-ring azepano-and 3,4-seco-fragments has been synthesized and evaluated for antiviral activity against influenza A(H1N1) virus. It was found that azepanodipterocarpol 8 and 3β-amino-28-oxoallobetulin 11 showed antiviral activity with IC 50 1.1 and 2.6 μg ml −1 , and selectivity index of 19 and 10, respectively.
Liquid tumor orthotopic xenograft models were established by intra femoral injection on NCG mice using freshly prepared leukemia cells from peripheral blood (PB) or bone marrow (BM) of AML/ALL patient samples. The establishment of the orthotopic models were monitored by the flow cytometry analysis of peripheral blood of engrafted mice:CD45+/CD33+ for AML and CD45+/CD19+ for B-ALL. The double positive cells in the peripheral blood of the successfully transplanted model can reach 5-15%. Typically, it takes 120 -170 days to establish the P0 AML orthotopic model. It takes 45-60 days to establish the P0 ALL orthotopic model. Spleen from engrafted P0 mice was used for P1-P3 reconstitution of the orthotopic model. On these orthotopic models, we tested whether medicines such as etoposide, cytarabine, vincristine, ibrutinib and imatinib are sensitive. And anti-CD47 antibody was also tested on these models. NGS profiling was used to confirm the genotype of established orthotopic PDX.
Citation Format: Hongkui Chen, Lintao Bi, Shizhu Zhao, Shuai Wang, Wenqiang Huang, Josh Caggiula, Loc Van, Danyi Wen. Liquid tumor orthotopic PDX models of acute leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3103.
Tumor cell immortalization through conditional reprogramming, particularly from limited biopsy specimen, is an invaluable tool to generate propagating tumor cells for cell-based diagnostics, drug sensitivity assay and bio-banking in vitro. We have successfully reprogrammed primary tumor cells from a number of unreported tumor types, including lung carcinoma and adenoid cystic carcinoma, towards immortalization. The propagating cells exhibited typical colonized growth, which is well maintained upon cryo-frozen. In some cases, the cells can be passaged for multiple times and likely become useful cell lines. Like primary tumor cells, conditional reprogrammed tumor cells are reliable to test drug sensitivity in vitro. We attempt to extend conditional reprogrammed tumor cells to reconstitute and grow PDX models in vivo for testing drug efficacy. Preliminary data indicate that, in a 7-day in vivo assay utilizing hollow-fiber tubes grown subcutaneously in mouse, which we call OncoVee Mini-PDX, conditional reprogrammed tumor cells, like primary tumor cells and PDX tumor cells, can be successfully used to test drug efficacy in vivo. In summary, this study explores and evaluates applications of conditional reprogrammed tumor cells in drug efficacy tests both in vitro and in vivo.
Citation Format: Yuan Long, Loc Van, Song Xi, Le Li, Yuhui Zheng, Ying Ling, Feifei Zhang, Jijun Cheng, Danyi Wen. Conditional tumor cell reprogramming: From in vitro sensitivity to in vivo PDX modeling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2164.
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