title: Cervical Cancer Patient-Derived Orthotopic Xenograft (PDOX) Is Sensitive to Cisplatinum and Resistant to Nab-paclitaxel.
abstract: 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.
authors.affiliation: AntiCancer, Inc., San Diego, CA, U.S.A.|Department of Surgery, University of California, San Diego, CA, U.S.A.|Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Murakami
authors.affiliation: Department of Obstetrics and Gynecology, Kawasaki Medical School, Okayama, Japan t.muratactac@gmail.com all@anticancer.com.
authors.forename: Takuya
authors.initials: T
authors.lastname: Murata
authors.affiliation: AntiCancer, Inc., San Diego, CA, U.S.A.|Department of Surgery, University of California, San Diego, CA, U.S.A.|Department of Surgery, Graduate School of Medicine, Tohoku University, Sendai, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Kawaguchi
authors.affiliation: AntiCancer, Inc., San Diego, CA, U.S.A.|Department of Surgery, University of California, San Diego, CA, U.S.A.|Department of Orthopedic Surgery, University of the Ryukyus, Okinawa, Japan.
authors.forename: Tasuku
authors.initials: T
authors.lastname: Kiyuna
authors.affiliation: AntiCancer, Inc., San Diego, CA, U.S.A.|Department of Surgery, University of California, San Diego, CA, U.S.A.|Department of Orthopedic Surgery, Kanazawa University, School of Medicine, Kanazawa, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Igarashi
authors.affiliation: AntiCancer, Inc., San Diego, CA, U.S.A.|Department of Surgery, University of California, San Diego, CA, U.S.A.|Department of Surgery, Division of Hepatobiliary and Pancreas Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Ho Kyoung
authors.initials: HK
authors.lastname: Hwang
authors.affiliation: Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Hiroshima
authors.affiliation: AntiCancer Japan Inc., Tokyo, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Hozumi
authors.affiliation: AntiCancer Japan Inc., Tokyo, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Komatsu
authors.affiliation: AntiCancer Japan Inc., Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kikuchi
authors.affiliation: Department of Surgery, University of California, San Diego, CA, U.S.A.
authors.forename: Thinzar M
authors.initials: TM
authors.lastname: Lwin
authors.affiliation: Department of Surgery, University of California, San Diego, CA, U.S.A.
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Delong
authors.affiliation: AntiCancer, Inc., San Diego, CA, U.S.A.|Department of Surgery, University of California, San Diego, CA, U.S.A.|Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Miyake
authors.affiliation: AntiCancer, Inc., San Diego, CA, U.S.A.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
authors.forename: Kuniya
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Department of Surgery, University of California, San Diego, CA, U.S.A.
authors.forename: Michael
authors.initials: M
authors.lastname: Bouvet
authors.affiliation: Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
authors.forename: Itaru
authors.initials: I
authors.lastname: Endo
authors.affiliation: AntiCancer, Inc., San Diego, CA, U.S.A. t.muratactac@gmail.com all@anticancer.com.|Department of Surgery, University of California, San Diego, CA, U.S.A.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoffman
mesh_terms: D000418:Albumins / Q000494:pharmacology*; D000818:Animals; D000969:Antinematodal Agents / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008819:Mice, Nude; D017239:Paclitaxel / Q000494:pharmacology*; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: C520255:130-nm albumin-bound paclitaxel; D000418:Albumins; D000969:Antinematodal Agents; D017239:Paclitaxel; D002945:Cisplatin
keywords: Cervical cancer; PDOX; cispatinum; drug response; nab-paclitaxel; nude mice; patient-derived othotopic xenograft