| BackgroundCadherin is a family of cell adhesion molecules that mediate calcium-dependent intercellular adhesion, and are involved in cell differentiation and morphogenesis. There are more than30kinds of identified cadherins distributing in different tissues, such as epithelial cadherin (E-cadherin), neural cadherin (N-cadherin), embryonic cadherin(P-cadherin) and so on. E-cadherin is a120KD transmembrane protein, encoded by the CDH1gene at16q22.1. E-cadherin can not only help establish calcium-dependent cell-cell contact through its extracellular domain, but also link the extracellular environment to the contractile cytoskeleton inside cells by the interaction of its short intracellular tail with catenins, which in turn bind to actin filaments and play an important role in certain nuclear responses. E-cadherin has been generally regarded as a tumor suppressor in various malignancies, such as lung, gastric, laryngeal, pancreatic, and bladder cancers. This is based on the fact that E-cadherin can prevent tumorigenesis, invasion, and Metastasis via promoting cell-cell adhesions and inhibiting epithelial-mesenchymal transition (EMT). However, a growing body of studies have recently emerged to challenge this view. For instance, E-cadherin is reported to be necessary for anchorage-independent growth and suppression of apoptosis in oral squamous cancer cells. Expression of the E-cadherin-catenin cell adhesion complex is shown to be vital for disease progression in primary squamous cell carcinomas of the head and neck and their nodal Metastases. Most importantly, E-cadherin appears to function differently in the development of ovarian cancers. E-cadherin is not expressed by the normal human ovarian surface epithelium (OSE), whereas it can be detected in the OSE located in the deep clefts, inclusion cysts, and invaginations, where over90%of the ovarian cancers arise. E-cadherin expression has been found in malignant ovarian tumors of all stages and its level is significantly higher in ovarian cancer tissues than in normal ovarian tissues. The above results suggest that the up-regulation of E-cadherin may be an early event in the initial development of ovarian epithelial cancers, which is opposite to its hypothesized role as a tumor suppressor. However, the mechanism that how E-cadherin plays its role during the development of ovarian cancer still remains unclear.ObjectiveE-cadherin, a classic tumor suppressor gene due to its prominent role in antagonizing metastasis, is unusually highly expressed in most ovarian cancers. This experiment was designed to study the possible role and mechanism of E-cadherin in the carcinogenesis and progression of ovarian cancers.MethodsE-cadherin gene CDH1was knocked down via RNA interference (RNAi) in an E-cadherin expressing ovarian cancer cell line SKOV-3and the following variation of its biological behavior was observed using CCK-8and colony formation experiment. Then, using a well-established cell model to study E-cadherin-mediated calcium-dependent cell-cell adhesion, the possible functions of E-cadherin in ovarian cancer and the related signal transduction pathway were investigated by Western blot.Results1. E-cadherin expression of ovarian cancer SKOV-3cells was down-regulated markedly after the RNAi targeting CDH1gene.2. Growth and proliferation of SKOV-3cells was efficiently suppressed after knocking-down of E-cadherin expression.3. E-cadherin promotes ovarian cancer cell proliferation through MEK/ERK signaling pathway.Conclusion1. E-cadherin may function as a tumor proliferation enhancer via activating MEK/ERK pathway in the development of ovarian epithelial cancers.2. Intervention of the critical members of E-cadherin-cell adhesions-MEK/ERK signaling pathway may inhibit the growth and proliferation of ovarian cancer, and that may provide a meaningful role in targeted therapy of ovarian cancer. Background and objectiveAlthough the term of neoadjuvant chemotherapy (NAC) in gastric cancer treatment was first reported in1989, Fujimoto S had reported the application of chemotherapy in gastric cancer before surgery in1967. But due to severe chemotherapy toxicity and other reasons, this trial didn’t attract more attention then. Recently the efficacy of NAC in the treatment of gastric cancer becomes attractive widely because of the poor outcome of gastric cancer, and a lot of clinical trials are carrying on, although the effects remain unclear. In this paper, we analyzed the published randomized clinical trials by meta-analysis, and evaluated the benefit of NAC in the treatment of locally advanced but resectable gastric cancer.MethodsElectronic databases including PubMed, MEDLINE, the Cochrane Library, ProQuest, and Elsevier were searched. The starting and ending time of electronic retrieval is from the time of building the database to February2012, the references of the literature have also been retrieved. For the randomized controlled clinical trials, efficacy and safety of neoadjuvant chemotherapy for advanced gastric cancer were studied and adopted. Then we evaluated the quality and extracted data one by one. We used STATA12.0for statistical analysis.ResultsA total of16randomized controlled trials including2340patients were enrolled, among which there were1189cases in NAC group and1151cases in control group that were lack of preoperative chemotherapy. Compared with the control group, the NAC group has no significant benefit of5-year survival rate (RR1.26,95%CI:0.99～1.60). While in the subgroup analysis, the benifit of5-year survival in NAC group was observed in Western countries (RR1.47,95%CI:1.18～1.84), but not in Eastern countries (RR1.12,95%CI:0.94～1.34). There was also significant increase of5-year survival with venous administration of drugs rather than oral or intraperitoneal usage (RR1.47,95%CI:1.18～1.84). HR of overall survival of NAC group is0.70(95%CI:0.55～0.88), lowering30%the risk of death compared with the control group. R0resection rate was significantly higher (RR1.18,95%CI:1.06～1.31) in NAC group. Subgroup analysis was performed for the presence of heterogeneity, which showed that there were improvement of R0resection rates in both western (RR1.08,95%CI:1.00～1.16) and eastern countries (RR1.39,95%CI:1.22～1.58), but the former had no statistical difference. The postoperative TO-2proportion was significantly higher (RR1.33,95%CI:1.13～1.58) in NAC group, while the postoperative incidence of complications showed no significant difference (RR1.25,95%,CI:0.83～1.88).Conclusion1. Neoadjuvant chemotherapy may improve the R0resection rate for locally advanced resectable gastric cancer and reduce tumor staging.2. Neoadjuvant chemotherapy may reduce hazard ratio (HR) of overall survival of locally advanced resectable gastric cancer and improve the5-year survival rate of patients in western countries.3. The intravenous administration of drugs for gastric cancer is an effective medication of neoadjuvant chemotherapy.4. Neoadjuvant chemotherapy does not increase postoperative complications of gastric cancer. |
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