Takashi Murakami1,2,3, Takuya Murata4, Kei Kawaguchi1,2,5, Tasuku Kiyuna1,2,6, Kentaro Igarashi1,2,7, Ho Kyoung Hwang1,2,8, Yukihiko Hiroshima3, Chihiro Hozumi9, Shin Komatsu9, Takashi Kikuchi9, Thinzar M Lwin2, Jonathan C Delong2, Kentaro Miyake1,2,3, Yong Zhang1, Kuniya Tanaka3, Michael Bouvet2, Itaru Endo3, Robert M Hoffman10,2. 1. AntiCancer, Inc., San Diego, CA, U.S.A. 2. Department of Surgery, University of California, San Diego, CA, U.S.A. 3. Graduate School of Medicine, Yokohama City University, Yokohama, Japan. 4. Department of Obstetrics and Gynecology, Kawasaki Medical School, Okayama, Japan t.muratactac@gmail.com all@anticancer.com. 5. Department of Surgery, Graduate School of Medicine, Tohoku University, Sendai, Japan. 6. Department of Orthopedic Surgery, University of the Ryukyus, Okinawa, Japan. 7. Department of Orthopedic Surgery, Kanazawa University, School of Medicine, Kanazawa, Japan. 8. Department of Surgery, Division of Hepatobiliary and Pancreas Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea. 9. AntiCancer Japan Inc., Tokyo, Japan. 10. AntiCancer, Inc., San Diego, CA, U.S.A. t.muratactac@gmail.com all@anticancer.com.
Abstract
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. Copyright
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 patienttumor. 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. Copyright
Authors: Yukihiko Hiroshima; Ali A Maawy; Matthew H G Katz; Jason B Fleming; Michael Bouvet; Itaru Endo; Robert M Hoffman Journal: J Surg Oncol Date: 2014-11-14 Impact factor: 3.454
Authors: Einar K Rofstad; Trude G Simonsen; Ruixia Huang; Lise Mari K Andersen; Kanthi Galappathi; Christine Ellingsen; Catherine S Wegner; Anette Hauge; Jon-Vidar Gaustad Journal: Cancer Lett Date: 2016-01-29 Impact factor: 8.679
Authors: Yukihiko Hiroshima; Ali Maawy; Yong Zhang; Takashi Murakami; Masashi Momiyama; Ryutaro Mori; Ryusei Matsuyama; Matthew H G Katz; Jason B Fleming; Takashi Chishima; Kuniya Tanaka; Yasushi Ichikawa; Itaru Endo; Robert M Hoffman; Michael Bouvet Journal: PLoS One Date: 2014-12-02 Impact factor: 3.240
Authors: Takashi Murakami; Arun S Singh; Tasuku Kiyuna; Sarah M Dry; Yunfeng Li; Aaron W James; Kentaro Igarashi; Kei Kawaguchi; Jonathan C DeLong; Yong Zhang; Yukihiko Hiroshima; Tara Russell; Mark A Eckardt; Jane Yanagawa; Noah Federman; Ryusei Matsuyama; Takashi Chishima; Kuniya Tanaka; Michael Bouvet; Itaru Endo; Fritz C Eilber; Robert M Hoffman Journal: Oncotarget Date: 2016-07-26
Authors: Takashi Murakami; Shukuan Li; Qinghong Han; Yuying Tan; Tasuku Kiyuna; Kentaro Igarashi; Kei Kawaguchi; Ho Kyoung Hwang; Kentaro Miyake; Arun S Singh; Scott D Nelson; Sarah M Dry; Yunfeng Li; Yukihiko Hiroshima; Thinzar M Lwin; Jonathan C DeLong; Takashi Chishima; Kuniya Tanaka; Michael Bouvet; Itaru Endo; Fritz C Eilber; Robert M Hoffman Journal: Oncotarget Date: 2017-05-30