Long-term Oncological Outcomes Of Rectal Cancer With And Without Preservation Of The Left Colic Artery And The Effect Of PTN Regulating Apoptosis Of Colorectal Cancer Cells

Chapter 1 Long-term oncological outcomes of rectal cancer with and without preservation of the left colic arteryObjective:There is uncertainty in the literature about preserving the left colic artery(LCA)during low anterior resection for rectal cancer.We analyzed the effect of preserving the LC A on long-term oncological outcomes.Methods:We retrospectively collected clinicopathological and follow-up details of patients who underwent low anterior resection for rectal cancer in the Gastrointestinal Surgery Department of Guangdong Provincial People’s Hospital,from January 2014 to December 2015.Cases were divided into low ligation(LL),LCA preserved,or high ligation(HL),LCA not preserved,of the inferior mesenteric artery.The 5-year overall survival(OS)and disease-free survival(DFS)rates were compared between the two groups.Results:Altogether,there were 221 and 295 cases in the LL group and HL groups,respectively.Operating time in the LL group was significantly longer than in the HL group(224.7 vs.211.7 min,P=0.039).Postoperative 30-day mortality,early complications including anastomotic leakage showed no significant diferences between the LL and HL groups(postoperative 30-day mortality,0.9%LL,1.4%HL,P=0.884;early complications,41.2%LL,38.3%HL,P=0.509;anastomotic leakage 8.6%LL,13.2%HL,P=0.100).The median follow-up periods were 51.4(7-61)months in the LL group and 51.2(8-61)months in the HL group.During follow-up,the percentages of patients who died,had local recurrence,or had metastases were 39.8%,7.7%,and 38.5%,respectively,in the LL group and 39%,8.5%,and 40%,respectively,in the HL group;these differences were not significant(all P>0.05).The 5-year OS and DFS were 69.6%and 59.6%in the LL group,respectively,and 69.1%and 56.2%in the HL group,respectively;these differences were not significant(all P>0.05).After stratification by tumor-node-metastasis stage,the difference between the 5-year OS and DFS for stages Ⅰ,Ⅱ,and Ⅲ cancer were not significant(all P>0.05).Conclusions:The long-term oncological outcomes of LL group are comparable with HL group.LL cannot be supported due to the absence of lower complication rates and the longer operating times.Chapter 2 The effect of PTN on apoptosis of colorectal cancer cellsObjective:Colorectal cancer is one of the most common malignant tumors of the digestive system,with morbidity and mortality accounting for the top three cancer types.Oxaliplatin plays an increasingly important role in 5-fluorouracil-based first-line treatment regimens,but frequently use of oxaliplatin will lead to drug resistance and serious adverse events,affecting its clinical application.In order to overcome the drug resistance and toxicity of oxaliplatin,chemical sensitizers are urgently needed.In previous studies,we found that Parthenolide can inhibit the growth and proliferation of colorectal cancer cells.On basis of previous studies,this study aims to explore the effect of Parthenolide inducing apoptosis of colorectal cancer cells,and to provide a new combination therapy concept for colorectal cancer.Methods:In vitro,we choose colorectal cancer cells sensitive strains S1,multiple drug-resistant strains S1-Ml-80,MTT method to detect the cell proliferation capacity,wound healing assay to detect cell migration ability,fluorescence microscope assay to detect reactive oxygen species(ROS)expression level,the flow cytometry assay to detect the cell cycle distribution,cell apoptosis and expressing of reactive oxygen species level,western blot assay to detect apoptosis-related proteins expression level.In vivo,the effect of Parthenolide on the growth of colorectal cancer was detected by tumor transplantation model in nude mice.Results:MTT assay and wound healing assay showed that Parthenolide could inhibit the proliferation and migration of colorectal cancer cells.Fluorescence microscope assay results showed that Parthenolide could enhance the expression level of reactive oxygen species.Flow cytometry assay results showed that Parthenolide could block the cell cycle of colorectal cancer in the G2/M phase and promote cell apoptosis through reactive oxygen species pathway.MTT assay,flow cytometry assay and western blot assay showed that the combination of Parthenolide and oxaliplatin could enhance the apoptosis effect of colorectal cancer cells and increase the expression level of apoptosis-related proteins.The results of tumor bearing experiments in nude mice showed that Parthenolide could inhibit the growth of transplanted tumor of CRC cell line S1 and drug-resistant cell line S1-M1-80.Conclusions:Parthenolide can enhance the killing effect of oxaliplatin on colorectal cancer cells,mainly by increasing the expression level of intracellular reactive oxygen species which lead to promoting cell apoptosis.