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Part1. SENP1Over-expression Predicts Chemo-sensitive And Poor Survival In Non-small Cell Lung Cancer Part2. Comparative Study Of Endoscopic Minimally Invasive Versus Traditional Open Esophagectomy For Esophageal Cancer

Posted on:2015-05-18Degree:DoctorType:Dissertation
Country:ChinaCandidate:J W MuFull Text:PDF
GTID:1224330467957608Subject:Oncology
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Part1. SENP1expression predicts chemo-sensitivity andsurvival in non-small cell lung cancerBackground Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors. Despite the advances in therapy over the years, its mortality remains high. The aim of this study was to evaluate the expression of SUMO proteases1(SENP1) in NSCLC tissues and its role in the regulation of vascular endothelial growth factor (VEGF) expression. We also investigated the association between the expression level of SENP1and the clinicopathological features and survival of the patients.Methods SENP1small interfering RNA (siRNA) was constructed and transfected into the NSCLC cells. VEGF gene expression was analyzed by real-time polymerase chain reaction (RT-PCR). Immunohistochemistry staining was used to assess the expression of SENP1in100NSCLC patients and its association with the clinicopathological features and survival was analyzed.Results VEGF expression was significantly higher in NSCLC tissues than in normal lung tissues. Inhibition of SENP1by siRNA was associated with decreased VEGF expression. SENP1was over-expressed in55of the100(55%) NSCLC samples and was associated with a moderate and low histological tumor grade (3.6%,38.2%, and58.2%in high, moderate and low differentiated samples, respectively, P=0.046), higher T stage (10.9%,89.1%, and0%in T1, T2and T3samples, respectively, P=0.003) and TNM stage (10.9%,61.8%, and27.3%in stage Ⅰ, Ⅱ,and Ⅲsamples, respectively, P<0.001). The rate of lymph node metastasis was significantly higher in the SENP1over-expression group (76.4%) than in the SENP1low expression group (33.3%, P<0.001). Among the34patients with SENP1over-expression,22(64.7%) developed recurrence or metastasis, significantly higher than those of the low expression group27.6%(8/29)(P=0.005). Multivariate cox-regression analysis showed that lymph node metastasis (P=0.015), TNM stage (P=0.001), and SENP1expression level (P=0.002) were independent prognostic factors for the survival of NSCLC patients.Conclusions SENP1may be used as a promising predictor of survival and as a predictive factor of chemo-sensitivity for NSCLC patients, potentially as a desirable drug target for lung carcinoma target therapy. Part2. Comparative study of endoscopic minimally invasive versus traditional open esophagectomy for esophageal cancerBackground It has been reported that incidence and mortality of esophageal cancer in China between2003and2007was highest in the world. Postoperative morbidity and mortality rate of esophagectomy is9%-29%and2%-4%in China, although lower than23%-50%and2%-8%in western countries. In order to minimize the injury reaction during the surgery and reduce the morbidity rate, hence reducing the mortality rate of esophagectomy, endoscopic minimally invasive esophagectomy (MIE) was introduced in our hospital. The aim of this study was to summarize the experiences of endoscopic MIE in our cancer center and compare the postoperative short-term outcomes in patients with esophageal squamous cell carcinoma undergoing endoscopic minimally invasive or traditional open esophagectomy (OE).Methods The medical records of182consecutive patients, who underwent endoscopic minimally invasive esophagectomy (MIE) between January2009and September2013in Cancer Institute&Hospital, Chinese Academy of Medical Sciences, were retrospectively reviewed. In the same period,144patients who underwent traditional OE, either Ivor Lewis or McKeown approach, were selected randomly as controls. The clinical variables of paired groups were compared, including age, sex, Charlson score, tumor location, duration of surgery, number of harvested lymph nodes, morbidity rate, the rate of leak, pulmonary morbidity rate, mortality rate, and hospital length of stay (LOS).Results The number of harvested lymph nodes was not significantly different between endoscopic MIE group and traditional OE group (median18vs.16, P=0.728). However, patients who underwent endoscopic MIE had longer operation time than the traditional OE group (375vs.300minutes, P<0.001). Overall morbidity, pulmonary morbidity, the rate of leak, in-hospital death, and hospital LOS were not significantly different between endoscopic MIE and traditional OE groups. However, patients who underwent endoscopic minimally Ivor Lewis esophagectomy had longer duration of surgery (420vs.270minutes, P<0.001) and more morbidity rate (21.2%vs.8.7%, P=0.034) than that of traditional open Ivor Lewis esophagectomy. And patients who underwent endoscopic minimally McKeown esophagectomy had longer duration of surgery (360vs.322minutes, P=0.003), but less overall morbidities (14.6%vs.26.9%, P=0.044) than that of traditional open McKeown esophagectomy. Multivariable analysis demonstrated that duration of surgery was the only independent factor predictive of postoperative morbidity(OR:1.004,95%CI:1.001-1.007, P=0.012), but not the approach of surgery.Conclusions Endoscopic MIE and traditional OE appears equivalent with regard to early oncological outcomes.
Keywords/Search Tags:SENP1protein, Non-small cell lung cancer, Prognosis, NeoplasmrecurrenceSurgical procedures, Minimally invasive, Esophagectomy, Comparative study
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