title: Establishment of a patient-derived orthotopic Xenograft (PDOX) model of HER-2-positive cervical cancer expressing the clinical metastatic pattern.
abstract: Squamous cell carcinoma of the cervix, highly prevalent in the developing world, is often metastatic and treatment resistant with no standard treatment protocol. Our laboratory pioneered the patient-derived orthotopic xenograft (PDOX) nude mouse model with the technique of surgical orthotopic implantation (SOI). Unlike subcutaneous transplant patient-derived xenograft (PDX) models, PDOX models metastasize. Most importantly, the metastasis pattern correlates to the patient. In the present report, we describe the development of a PDOX model of HER-2-positive cervical cancer. Metastasis after SOI in nude mice included peritoneal dissemination, liver metastasis, lung metastasis as well as lymph node metastasis reflecting the metastatic pattern in the donor patient. Metastasis was detected in 4 of 6 nude mice with primary tumors. Primary tumors and metastases in the nude mice had histological structures similar to the original tumor and were stained by an anti-HER-2 antibody in the same pattern as the patient's cancer. The metastatic pattern, histology and HER-2 tumor expression of the patient were thus preserved in the PDOX model. In contrast, subcutaneous transplantation of the patient's cervical tumors resulted in primary growth but not metastasis.
authors.affiliation: AntiCancer, Inc., San Diego, CA, United States of America; Department of Surgery, University of California San Diego, San Diego, CA, United States of America; Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Hiroshima
authors.affiliation: AntiCancer, Inc., San Diego, CA, United States of America.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: AntiCancer, Inc., San Diego, CA, United States of America.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Surgery, University of California San Diego, San Diego, CA, United States of America.
authors.forename: Ali
authors.initials: A
authors.lastname: Maawy
authors.affiliation: AntiCancer, Inc., San Diego, CA, United States of America; Department of Surgery, University of California San Diego, San Diego, CA, United States of America.
authors.forename: Sumiyuki
authors.initials: S
authors.lastname: Mii
authors.affiliation: AntiCancer, Inc., San Diego, CA, United States of America; Department of Surgery, University of California San Diego, San Diego, CA, United States of America.
authors.forename: Mako
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: AntiCancer, Inc., San Diego, CA, United States of America; Department of Surgery, University of California San Diego, San Diego, CA, United States of America.
authors.forename: Fuminari
authors.initials: F
authors.lastname: Uehara
authors.affiliation: AntiCancer, Inc., San Diego, CA, United States of America; Department of Surgery, University of California San Diego, San Diego, CA, United States of America.
authors.forename: Shinji
authors.initials: S
authors.lastname: Miwa
authors.affiliation: AntiCancer, Inc., San Diego, CA, United States of America; Department of Surgery, University of California San Diego, San Diego, CA, United States of America.
authors.forename: Shuya
authors.initials: S
authors.lastname: Yano
authors.affiliation: AntiCancer, Inc., San Diego, CA, United States of America; Department of Surgery, University of California San Diego, San Diego, CA, United States of America; Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Murakami
authors.affiliation: Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Momiyama
authors.affiliation: Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Chishima
authors.affiliation: Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Kuniya
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ichikawa
authors.affiliation: Department of Surgery, University of California San Diego, San Diego, CA, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Bouvet
authors.affiliation: Department of Obstetrics and Gynecology, Kawasaki University Medical School, Kawasaki, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Murata
authors.affiliation: Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Itaru
authors.initials: I
authors.lastname: Endo
authors.affiliation: AntiCancer, Inc., San Diego, CA, United States of America; Department of Surgery, University of California San Diego, San Diego, CA, United States of America.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoffman
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology*
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human