Comparison of the Clinicopathological Features in Small Bile Duct and Bile Ductular Type Intrahepatic Cholangiocarcinoma
ANTICANCER RESEARCH
Authors: Yamada, Mihoko; Yamamoto, Yusuke; Sugiura, Teiichi; Kakuda, Yuko; Ashida, Ryo; Tamura, Shunsuke; Okamura, Yukiyasu; Ito, Takaaki; Ohgi, Katsuhisa; Nakanuma, Yasuni; Uesaka, Katsuhiko
Abstract
Background: The classification of intrahepatic cholangiocarcinomas (ICCs) has been reported in several studies, however, it remains controversial. Materials and Methods: Between January 2003 and December 2015, 94 patients underwent hepatectomy for ICC. The ICCs of 63 of these patients were classified as predominantly small bile duct type or bile ductular type ICC and were included in this analysis. Results: Thirty-seven patients (58.7%) were classified into the small bile duct ICC group, and 26 (41.3%) into the bile ductular ICC group. A multivariate analysis identified intrahepatic metastasis [hazard ratio (HR)=2.53, p=0.011], small bile duct ICC (HR=2.05, p=0.046) and portal vein invasion (HR 2.05, p=0.047) as independent prognostic factors for poorer survival. Conclusion: It is important to correctly distinguish between small bile duct and bile ductular ICC types because these two types clearly have different clinicopathological and prognostic features.
Chronic Cadmium Exposure in Vitro Causes Acquisition of Multiple Tumor Cell Characteristics in Human Pancreatic Epithelial Cells
ENVIRONMENTAL HEALTH PERSPECTIVES
Authors: Qu, Wei; Tokar, Erik J.; Kim, Andrew J.; Bell, Matthew W.; Waalkes, Michael P.
Abstract
BACKGROUND: Cancer may be a stem cell (SC)-based disease involving formation of cancer SCs (CSCs) potentially arising from transformation of normal SCs. Cadmium has been linked to human pancreatic cancer. OBJECTIVE: We studied cadmium exposure of human pancreatic ductal epithelial (HPDE) cells and whether SCs may be targeted in this process. METHODS: We chronically exposed HPDE cells to low level cadmium (1 mu M) for 5 29 weeks. Non-adherent spheroid formation was used to indicate CSC-like cell production, and we assessed tumor cell characteristics in such spheres. Assessed tumor cell characteristics including secretion of matrix metalloproteinase-9 (MMP-9), invasion, and colony formation were fortified by evaluating expression of relevant genes by real-time reverse transcription polymerase chain reaction and by Western blot. RESULTS: Increased MMP-9 secretion and overexpression of the pancreatic cancer marker S100P occurred in chronic (29 weeks of exposure) cadmium-exposed (CCE) cells. CCE cells also showed markedly higher colony formation and invasion, typical of cancer cells. Floating "spheres" of viable cells, known to contain an abundance of normal SCs or CSCs, form in vitro with many cell types. CCE cells produced 3-fold more spheres than control cells and were more invasive, secreted more MMP-9, and overexpressed markers for pancreatic SCs/CSCs (i.e., CXCR4, OCT4, CD44) and S100P, a marker for pancreatic cancer. CCE-derived spheres rapidly produced aggressive, highly branched, and poorly differentiated glandular-like structures in Matrigel. CONCLUSIONS: Chronic cadmium exposure produced multiple tumor cell characteristics in HPDE cells and CCE cell derived spheres. These data support the plausibility of cadmium as a human pancreatic carcinogen.