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Cervical Cancer Patient-Derived Orthotopic Xenograft (PDOX) Is Sensitive to Cisplatinum and Resistant to Nab-paclitaxel.
- Murakami, Takashi;
- Murata, Takuya;
- Kawaguchi, Kei;
- Kiyuna, Tasuku;
- Igarashi, Kentaro;
- Hwang, Ho Kyoung;
- Hiroshima, Yukihiko;
- Hozumi, Chihiro;
- Komatsu, Shin;
- Kikuchi, Takashi;
- Lwin, Thinzar M;
- Delong, Jonathan C;
- Miyake, Kentaro;
- Zhang, Yong;
- Tanaka, Kuniya;
- Bouvet, Michael;
- Endo, Itaru;
- Hoffman, Robert M
Published Web Location
https://doi.org/10.21873/anticanres.11289Abstract
Background
Cervical cancer is a world-wide problem that requires transformative therapeutic strategies. We have previously developed patient-derived orthotopic xenograft (PDOX) nude-mouse models of this disease. In the present report, we demonstrate that the standard drug, cisplatinum (CDDP), is highly-effective while the new, highly-touted agent, nab-paclitaxel (NAB-PTX) is ineffective.Materials and methods
Cervical PDOX tumors were grown on the cervix of nude mice for 4 weeks after surgical orthotopic implantation (SOI). Tumors were treated with CDDP or NAB-PTX.Results
H&E staining demonstrated that the PDOX tumor recapitulated the original patient tumor. CDDP was highly-effective. One tumor that was treated with CDDP completely regressed. CDDP-treated tumors were smaller (tumor volume ratio: 0.42±0.36) than the control group (tumor volume ratio: 3.47±1.66) (p<0.01). In contrast, NAB-PTX did not show significant efficacy on the cervical cancer PDOX model (tumor volume ratio: 2.85±1.45) (p=0.47). CDDP-treated tumor weight (50±50 mg) was significantly less than control (238±114 mg) (p<0.01). NAB-PTX-treated tumors were not reduced in weight (246±136 mg) compared to control (p=0.91). There were no significant differences in mouse body weight between groups. Histological evaluation demonstrated that CDDP-treated tumors were fibrotic with scattered squamous cell nests compared to control or NAB-PTX-treated tumors.Conclusion
The results of the present study demonstrate the power of PDOX models of cervical cancer to distinguish efficacy of potential therapeutics for individual patients with this disease.Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.