Background:The purpose of this study was to detect postoperative persistent circulating tumour cells (CTCs) in stages II and III colon cancer patients undergoing curative resection and so identify a subgroup of patients who are at high risk for early relapse.Methods:Four mRNA molecular markers including human telomerase reverse transcriptase, cytokeratin-19, cytokeratin-20, and carcinoembryonic antigen (CEA) mRNA were used to detect CTCs in 141 stages II and III colon cancer patients undergoing curative resection to determine the significance of CTCs in postoperative early relapse.Results:Out of 141 patients, postoperative early relapse and non-early relapse/no relapse was found in 48 (34.0%) patients and 93 (66.0%) patients, respectively. Univariately, postoperative early relapse was significantly correlated with lymph node metastasis (P=0.025), vascular invasion (P=0.002), perineural invasion (P=0.001), laparoscopic surgery (P=0.019), high postoperative serum CEA levels (P=0.001), and presence of persistent postoperative CTCs (P<0.001). Using a multivariate proportional hazards regression analysis, the presence of perineural invasion (P=0.034; HR, 1.974; 95% CI: 1.290–3.861), high postoperative serum CEA levels (P=0.020; HR, 2.377; 95% CI: 1.273–4.255), and the presence of persistent postoperative CTCs (P<0.001; HR, 11.035; 95% CI: 4.396–32.190), were demonstrated to be independent predictors for postoperative early relapse. Furthermore, the presence of persistent postoperative CTCs was strongly correlated with a poorer disease-free and overall survival (both P<0.001).Conclusions:This study suggests that molecular detection of persistent postoperative CTCs is a prognostic predictor of early relapse in UICC stage II/III colon cancer patients, and thus could help to define patients with this tumour entity for an enhanced follow-up and therapeutic program.
Among 104 cases of squamous-cell oesophageal carcinoma patients and 277 controls in Taiwan, after adjusting for cigarette smoking, alcohol consumption, and other confounders, we found that subjects who chewed from 1 to 495 betel-year and more than 495 betel-years (about 20 betel quid per day for 20 years) had 3.6-fold (95% Cl = 1.3–10.1) and 9.2-fold risk (95% Cl = 1.8–46.7), respectively, of developing oesophageal cancer, compared to those who did not chew betel. © 2001 Cancer Research Campaign http://www.bjcancer.com
The androgen receptor (AR) has a critical role in promoting androgen-dependent and -independent apoptosis in testicular cells. However, the molecular mechanisms that underlie the ligand-independent apoptosis, including the activity of AR in testicular stem cells, are not completely understood. In the present study, we generated induced pluripotent stem cells (iPSCs) from bovine testicular cells by electroporation of octamer-binding transcription factor 4 (OCT4). The cells were supplemented with leukemia inhibitory factor and bone morphogenetic protein 4, which maintained and stabilized the expression of stemness genes and pluripotency. The iPSCs were used to assess the apoptosis activity following exposure to phthalate esters, including di (2-ethyhexyl) phthalates, di (n-butyl) phthalate, and butyl benzyl phthalate. Phthalate esters significantly reduced the expression of AR in iPSCs and induced a higher ratio of BAX/BCL-2, thereby favoring apoptosis. Phthalate esters also increased the expression of cyclin-dependent kinase inhibitor 1 (p21Cip1) in a p53-dependent manner and enhanced the transcriptional activity of p53. The forced expression of AR and knockdown of p21Cip1 led to the rescue of the phthalate-mediated apoptosis. Overall, this study suggests that testicular iPSCs are a useful system for screening the toxicity of environmental disruptors and examining their effect on the maintenance of stemness and pluripotency, as well as for identifying the iPSC signaling pathway(s) that are deregulated by these chemicals.
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