title: Comprehensive characterization of chemotherapeutic efficacy on metastases in the established gastric neuroendocrine cancer patient derived xenograft model.
abstract: The HuPrime® human gastric neuroendocrine carcinoma derived xenograft model GA0087 was established in this study. GA0087 PDX model showed high gene expression of vascular endothelial growth factors (VEGF)-A and B, and high potential of lung metastasis. Circulating tumor cells (CTCs) with either large or small size, circulating tumor microemboli (CTM) and lung metastatic lesions were detected in GA0087 PDX mice. The number of CTC correlated to the number of metastatic nodules in lung. Both primary tumor growth and metastasis in terms of the number of dynamically monitored CTCs and metastatic nodules were effectively suppressed by Cisplatin. Diverse subtypes of CTCs in the context of sensitivity to Cisplatin were specifically identified by subtraction enrichment (SE) integrated with in situ Phenotyping of cytokeratin 18 (CK18) and Karyotyping of chromosome 8 (in situ PK CTC by CK-iFISH). All the CK18-/diploid and majority of CK18+/diploid CTC subtypes were chemosensitive, whereas a higher percentage of CK18+/multiploid subtype of CTC were Cisplatin-insensitive. Combined histopathological examination of metastatic lesion and in situ PK CTC in a metastatic PDX (mPDX) tumor model are of particular significance, and may provide an unique and robust platform for cancer research as well as pre-clinical evaluation of therapeutic efficacy of new anti-cancer drugs.
authors.affiliation: Crown Bioscience, Santa Clara, California, USA.
authors.forename: Jiahua
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Cytelligen, San Diego, California, USA.
authors.forename: Daisy Dandan
authors.initials: DD
authors.lastname: Wang
authors.affiliation: Crown Bioscience, Santa Clara, California, USA.
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Yang
authors.affiliation: Crown Bioscience, Santa Clara, California, USA.
authors.forename: Dawei
authors.initials: D
authors.lastname: Chen
authors.affiliation: Crown Bioscience, Santa Clara, California, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Pang
authors.affiliation: Crown Bioscience, Santa Clara, California, USA.
authors.forename: Sheng
authors.initials: S
authors.lastname: Guo
authors.affiliation: Crown Bioscience, Santa Clara, California, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Cai
authors.affiliation: Crown Bioscience, Santa Clara, California, USA.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Wery
authors.affiliation: Cytelligen, San Diego, California, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Li
authors.affiliation: Crown Bioscience, Santa Clara, California, USA.|State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, China.
authors.forename: Henry Qixiang
authors.initials: HQ
authors.lastname: Li
authors.affiliation: Cytelligen, San Diego, California, USA.
authors.forename: Peter Ping
authors.initials: PP
authors.lastname: Lin
mesh_terms: D000368:Aged; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism; D018278:Carcinoma, Neuroendocrine / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D004195:Disease Models, Animal; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D013274:Stomach Neoplasms / Q000473:pathology*; D014183:Transplantation, Heterologous; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis; D042561:Vascular Endothelial Growth Factor B / Q000096:biosynthesis
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D042461:Vascular Endothelial Growth Factor A; D042561:Vascular Endothelial Growth Factor B; C467480:vascular endothelial growth factor A, mouse; C467482:vascular endothelial growth factor B, mouse; D002945:Cisplatin
keywords: CTC subtypes; chemoresistance; iFISH; in situ phenotyping and karyotyping; metastatic PDX