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Quality Of Life Of Obese Patients With Esophageal Cancer And The Molecular Biology Of FOXP3 Expressed By Tumor Cells

Posted on:2019-03-09Degree:MasterType:Thesis
Country:ChinaCandidate:N ZhangFull Text:PDF
GTID:2394330545953607Subject:Nursing
Abstract/Summary:PDF Full Text Request
(1)Objectives:To explore the influence of obesity on short-term of nutrition and immunity,complications and quality of life in postoperative patients with esophageal cancer.Methods:We adopted a cohort study and patients data were collected retrospectively and prospectively.Patients were restricted to who adopted radical resection of esophageal cancer.Data collection included demographic data(age,gender,occupation,marital status,weight,smoking history,drinking history),and disease-related information(total cholesterol,triglyceride,albumin,TNM stage,pathological types,location,comorbidities,level of anesthesia,ventilation reservation and forced expiratory volume in one second ratio).We divided patients into two groups according to their body mass index.The preoperative and postoperative quality of life,level of complications and specific kinds of complications were collected and analyzed.Health-related quality of life(HRQL)was assessed before surgery and six months after surgery using the validated European Organisation for Research and Treatment of Cancer(EORTC)Quality of Life Questionnaire C30 and QLQ-OES18.Propensity score-matching was used to adjustment.Nutritional status,complications,and quality of life were analysed after matching.Multivariate linear regression was used to analyze the factorsof quality of life influenced postoperative weight change.Results:(1)Total 343 patients were included in this study.Of these individuals,109 were obese patients and 234 were normal weight patients.Multiterm demographics and disease-related factors were significant difference between obese group and normal weight group,including gender(?2=5.346,P<0.05),smoking(?2=4.954,P<0.05),triglycerides(t=-2.570,P<0.05),albumin(t=-3.755,P<0.001),comorbidities(?2=8.759,P<0.05),diabetes(?2=9.371,P<0.05),hypertension(?2=4.168,P<0.05)and ventilation reserves(t=2.590,P<0.05).(2)There was no statistical significant difference between the prealbumin,hemoglobin,absolute value of lymphocytes and length of stay in the obese group compared with the normal weight group.However,the average weight loss between two groups(11.96 vs 6.81)was statistically significant.The descend range of weight loss ? 10%in obesity patients occupied 57.2%while in normal weight patients occupied 42.8%(P<0.001).(3)The level of complications was comparable between obese group and normal weight group.There were also no significant difference in the incidence of pulmonary infection,hydrothorax and chylothorax.However,obese patients showed higher anastomotic fistula incidence than normal weight patients(?2=10.812,P=0.001)(4)In the baseline comparison of QoL,obese patients had worse global quality of life and physical function.In the 6-month after operation,obese group had significant lower global quality of life than normal weight patients(62.08 vs 65.94,P<0.05),physical function(72.23 vs 78.32,P<0.05),and social function(68.35 vs 75.15,P<0.05).Fatigue(35.17 vs 27.67,P<0.001),diarrhea(27.83 vs 19.72,P<0.05),eating problems(28.82 vs 23.97,P<0.05),esophageal pain(26.71 vs 20.44,P<0.05)and taste problems(27.83 vs 21.25,P<0.05)were clinically and statistically significant deteriorated throughout the obese patients.(5)Weight loss could aggravate multiaspects of QOL.The more the weight loss,the lower the physical function((P=-0.40,P<0.001)was,the more serious fatigue(?=0.19;,P<0.05)was,the more problems with eating(P=0.24,P<0.05),the heavier esophageal pain(?=0.27,P<0.001)and taste problems(?=0.26,P<0.001).Anastomotic fistula could also aggravate the fatigue symptom(?=0.15,P<0.05).Conclusion:(1)Obesity does not affect the short-term immune or nutrition statusor the severity of complications,but it could increase the incidence of anastomotic fistula.(2)Obesity could aggravate the postoperative fatigue of patients with esophageal cancer and affect the nutritional status,resulting in an increased risk of malnutrition.(3)Reasonable preoperative weight loss strategy and postoperative nutrition support care are necessary for obese patients with esophageal cancer.Meanwhile,postoperative observation of anastomotic fistula of obese patients should be strengthened.(2)Objectives:To explore the effect of FOXP3 expressed by esophagus cancer cells on cytokines and lymphocyte differentiation in tumor microenvironment.Methods:Real-time quantitative PCR and western blot were used to determine the content of FOXP3 expression in esophageal cancer cell lines.Plasmid vector and virus vector were used to change the expression level of FOXP3.The cancer cells transfected before and after were co-cultured with peripheral blood lymphocytes for 72 hours and supernate were collected in 24 hours,48 hours and 72 hours,respectively.Centrifugation was used to sepatate the liquid supernatant and suspending lymphocytes and stored at-20? and 4?,respectively.Enzyme-linked immuno sorbent assay was used to determine the content change of TGF-?,IFN-?,TNF-?,IL-23,IL-1? and IL-10 in microenvironment.Flow cytometry was used to detect the differentiation of lymphocytes including the proportion of CD4+CD25+FOXP3+ T cells and CD8+CD28+ T cells.Compared the number of esophagus cancer cells harvested 72 hours after co-culture.Results:(1)The expression of FOXP3 gene was highest in Te-1 esophagus cancer cell lines and lowest in KYSE450 esophagus cancer cell lines.The difference was about four to five times.Therefore,the KYSE450 cell line was the overexpression system of plasmid transfection and TE-1 was the lowexpression system of virus interference.(2)In the overexpression system,the expression level of IFN-y was decreased,TGF-P and IL-10 expression were increased in transfected KYSE450 cell line.The difference between over expression group and control group was statistically significant.In the low expression system,the expression level of IFN-y was increased,but TGF-? and IL-10 expression were decreased in transfected TE-1 cell line.The difference between low expression group and control group was statistically significant.However,the content of TNF-a,IL-1 and IL-23 was not affected by the change of expression of FOXP3 gene.The results of direct co-culture system and indirect co-culture system were consistent,and there was no statistical difference between the two co-culture systems.(3)In the overexpression system,the increased expression level of FOXP3 gene converted the lymphocytes to CD4+CD25+FOXP3+ T cells increaseedly,while the conversion of CD8+CD28+ T cells was less-Transfection group was obviously higher than that of control group,the difference was statistically significant.In the low expression system,the decreased expression level of FOXP3 gene converted the lymphocytes to CD8+CD28+ T cells increaseedly,while the conversion of CD4+CD25+FOXP3 T cells was less.The difference between transfection group and control groupwas obviously and statistically significant.The results of direct co-culture system and indirect co-culture system were consistent,and there was no statistical difference between the two co-culture systems.(4)Co-cultured after 72 hours,the living cells were harvested.The amount of cancer cells in transfected group of the overexpression system was significant higher than that in the control group,while in the low expression system it was lower than that in the control group.Conclusion:(1)The overexpression of FOXP3 gene in esophagus cancer cell line could reduce the secretion of IFN-gamma,increase the secretion of TGF-? and IL-10.High expression of FOXP3 gene of cancer cell also increase the convertion to Treg but decrease the convertion to CTL.This change made a microenvironment in favour of tumor growth and metastasis.It alsoinhibited the body anti-tumor effect.(2)The low expression of FOXP3 gene in esophagus cancer cell line could reduce the secretion of TGF-? and IL-10,increase the secretion of IFN-?.Lowexpression of FOXP3 gene of cancer cell also decreases the convertion to Treg but increase the convertion to CTL.Therefore,it promotes tumor apoptosis,inhibits tumor growth and metastasis,and strengthens the ability to resist immune escape.
Keywords/Search Tags:Esophageal cancer, Quality of life, Obese, Transcription factors, T-lymphocytes, Cytokines
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