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
AntiCancer, Inc., San Diego, CA, U.S.A.
Department of Surgery, University of California, San Diego, CA, U.S.A.
Anticancer Res. 2017 Jan;37(1):61-65. doi: 10.21873/anticanres.11289.
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.
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.
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.
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.
宫颈癌是一个全球性问题,需要变革性的治疗策略。我们之前已建立了该疾病的患者来源原位异种移植(PDOX)裸鼠模型。在本报告中,我们证明标准药物顺铂(CDDP)高度有效,而新的、备受吹捧的药物纳米白蛋白结合型紫杉醇(NAB-PTX)无效。
手术原位植入(SOI)后,将宫颈PDOX肿瘤在裸鼠宫颈上生长4周。肿瘤用CDDP或NAB-PTX治疗。
苏木精-伊红(H&E)染色显示PDOX肿瘤重现了原始患者肿瘤的特征。CDDP高度有效。一个接受CDDP治疗的肿瘤完全消退。CDDP治疗的肿瘤比对照组小(肿瘤体积比:0.42±0.36)(对照组肿瘤体积比:3.47±1.66)(p<0.01)。相比之下,NAB-PTX对宫颈癌PDOX模型未显示出显著疗效(肿瘤体积比:2.85±1.45)(p=0.47)。CDDP治疗的肿瘤重量(50±50mg)明显低于对照组(238±114mg)(p<0.01)。与对照组相比,NAB-PTX治疗的肿瘤重量未减轻(246±136mg)(p=0.91)。各组小鼠体重无显著差异。组织学评估表明,与对照组或NAB-PTX治疗的肿瘤相比,CDDP治疗的肿瘤呈纤维化,有散在的鳞状细胞巢。
本研究结果证明了宫颈癌PDOX模型在区分该疾病个体患者潜在治疗药物疗效方面的作用。