| Autor: |
John D. Karalis, Lynn Y. Yoon, Suntrea T. G. Hammer, Changjin Hong, Min Zhu, Ibrahim Nassour, Michelle R. Ju, Shu Xiao, Esther C. Castro-Dubon, Deepak Agrawal, Jorge Suarez, Scott I. Reznik, John C. Mansour, Patricio M. Polanco, Adam C. Yopp, Herbert J. Zeh, Tae Hyun Hwang, Hao Zhu, Matthew R. Porembka, Sam C. Wang |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Journal of Translational Medicine, Vol 20, Iss 1, Pp 1-13 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
1479-5876 |
| DOI: |
10.1186/s12967-022-03317-7 |
| Popis: |
Abstract Background Lenvatinib is a multitargeted tyrosine kinase inhibitor that is being tested in combination with immune checkpoint inhibitors to treat advanced gastric cancer; however, little data exists regarding the efficacy of lenvatinib monotherapy. Patient-derived xenografts (PDX) are established by engrafting human tumors into immunodeficient mice. The generation of PDXs may be hampered by growth of lymphomas. In this study, we compared the use of mice with different degrees of immunodeficiency to establish PDXs from a diverse cohort of Western gastric cancer patients. We then tested the efficacy of lenvatinib in this system. Methods PDXs were established by implanting gastric cancer tissue into NOD.Cg-Prkdc scid Il2rg tm1Wjl /SzJ (NSG) or Foxn1 nu (nude) mice. Tumors from multiple passages from each PDX line were compared histologically and transcriptomically. PDX-bearing mice were randomized to receive the drug delivery vehicle or lenvatinib. After 21 days, the percent tumor volume change (%Δvtumor) was calculated. Results 23 PDX models were established from Black, non-Hispanic White, Hispanic, and Asian gastric cancer patients. The engraftment rate was 17% (23/139). Tumors implanted into NSG (16%; 18/115) and nude (21%; 5/24) mice had a similar engraftment rate. The rate of lymphoma formation in nude mice (0%; 0/24) was lower than in NSG mice (20%; 23/115; p |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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