| Background and objective: The incidence and mortality of gastric cancer in China are higher than the world average.China's cancer statistics show that more than 300,000 people die from gastric cancer each year.The low survival rate of gastric cancer is mainly due to its low early detection rate.Many patients have lost the opportunity of surgery at the time of diagnosis,or recurred after radical resection.Once transferred,the patient has a poor prognosticity and a medium survival time of about 1 year.Although advance stage gastric cancer first-line chemotherapy can be carried out until the disease develops,the duration of combined chemotherapy may be limited by toxicity.Therefore,the treatment of stomach cancer,especially advanced metastatic stomach cancer,is still an area for further research,and all treatment options All need new effective treatment strategies to improve.Prostate stem cell antigen(PSCA)is located on autosomal 8q24.It encodes PSCA polypeptides,a cell surface protein anchored by lysophosphatidic inositol,containing 123 amino acid residues belonging to the Thy-1/LY-6 family.Studies have shown that PSCA may be involved in cell signal transduction and proliferation regulation,but its defined physiological functions and regulatory mechanisms in normal and tumor cells are still unknown.Futhermore,the present study is intended to investage the interaction and mechanism of common chemotherapy oxaliplatin and 5-fluorouracine commonly used in gastric cancer from cell level,molecular level,and to study the effects of gastric cancer with peritoneal metastasis in combination with oxaliplatin and 5-fluorouracil intraperitoneal hyperthermic perfusion chemotherapy(IHPC)in PSCA population,to explore the efficacy and safety of the treatment of advanced gastric cancer,and to provide information and support for the treatment of advanced gastric cancer.Materials and Methods: 1.The influence of PSCA gene polymorphism on regulating the risk of gastric cancer in Chinese population Questionnaire survey method was used to calculate the general information of the research subjects,including gender composition,age,ethnicity,smoking time and number of cigarettes,drinking time and amount,living habits,family disease history,basic information of gastric cancer patients(diagnosis,staging,pathology)Type,etc.).Smoking is defined as the number of drinking is defined as ?3 times a week,and the cumulative drinking time is ?1 year;cigarettes smoked per day ?1,and the cumulative smoking time is ?1 year.Specimen collection: After the patient is fasted for 12 hours and rested for 1 hour in the next morning,5 ml of venous blood is collected with a disposable blood collection device,placed in an EDTA anticoagulant tube,and the experimental genomic RNA was collected and cryopreserved at-80?.2.The inhibitory effect of oxaliplatin + 5-fluorouracil on gastric cancer cell line MGC-803 and the drug-drug interaction(1)CCK-8 detects the effect of oxaliplatin + 5-fluorouracil on the cell viability of stomach cancer cell line MGC-803.(2)The effect of oxaliplatin + 5-fluorouracil on the cloning ability of gastric cancer cell line MGC-803.(3)DAPI detects the effect of oxaliplatin + 5-fluorouracil on the gastric cancer cell line MGC-803 apoptosis.(4)The effect of oxaliplatin + 5-fluorouracil on the apoptosis of gastric cancer cell line MGC-803 was detected by flow cytometry.(5)The effect of oxaliplatin + 5-fluorouracil on the cell cycle of gastric cancer cell line MGC-803 was detected by flow cytometry.(6)The Bcl-2,VEGF,NF-?B and PSCA m RNA expression of oxaliplatin + 5-fluorouracil on the gastric cancer cell line MGC-803 was evaluated by q RT-PCR.(7)Western Blot detects the effect of oxaliplatin + 5-fluorouracil on Bcl-2,VEGF,NF-?B and PSCA protein of gastric cancer cell line MGC-803.3.Observation of the efficacy of intraperitoneal hyperthermic perfusion chemotherapy in combination with Oxaliplatin platinum plus 5-Fluorouracil to treat peritoneal carcinoma of stomach cancer with PSCA(1)In this study,from March 2013 to March 2016,a total of 90 gastric cancer with peritoneal metastasis patients of the PSCA population were hospitalized,who were successfully identified by laparoscopy. (2)All cases successfully underwent laparoscopy to identify gastric cancer with peritoneal metastasis by pathology.In the control group,a conventional drainage tube was placed,the abdominal cavity was closed layer by layer,and routine anti-infection,pain relief,intravenous nutritional support and other treatments were performed after the operation.Regular chemotherapy and follow-up was performed according to CSCO.In the IHPC group,silicone catheters with multiple side holes were placed on the diaphragm surface,nasal cavity,and pelvic cavity of the liver for drainage after surgery,and fixed on the upper right abdomen,upper left abdomen,and lower left abdomen wall,respectively.In addition,Oxaliplatin(200mg)and 5-fluorouracil(1000mg)were divided into two doses,which was performed Sequentially in intraperitoneal perfusion chemotherapy,repeated every other day,a total of 4 times.Connect the extracorporeal circulation tubing to the hyperthermia chemotherapy machine(BR-TRG-I,Guangzhou Baorui Medical Technology Co.,Ltd.,Guangzhou,China).After installing the corresponding temperature measuring device,2000 m L of 5% glucose solution with 100 mg of Oxaliplatin or 2000 m L of 0.9% Sodium chloride solution with 500 mg of 5-FU is added to the filling bag,and the circulation pump and heating system are started.Subsequently,when the temperature of the chemotherapy solution stabilizes to 38°C,the drainage is connected to the extracorporeal circulation pipeline,the perfusion rate is adjusted to 500 m L/min,and the temperature gradually rises to allow the patient to adapt to the environment,and the temperature is controlled at 43°C for 60 minutes.After that,the volume of residual fluid in the abdominal cavity is allowed to be less than 1500 m L,the connection between the circulation pipe and the drainage pipe is relieved,and the drainage pipe is connected to the low negative pressure drainage bag.Regular chemotherapy and follow-up was performed?Results: 1.The influence of PSCA gene polymorphism on regulating the risk of gastric cancer in Chinese population(1)PSCA is expressed during the differentiation of gastric cortical cells and has the effect of inhibiting the proliferation of stomach cancer cells,but silence is expressed in gastric cancer cells.In addition,the PSCA gene rs2294008T/C polymorphism is related to the occurrence of gastric cancer,and the T allele can increase the risk of intestinal,poorly differentiated,non-cardia gastric cancer.(2)The study included 549 gastric cancer patients and 592 healthy symptomatic patients.The age and gender of the subjects are well matched.There was no significant difference between case and age control(59.22 ±10.94 vs.58.45± 11.74,P=0.421)and gender(P=0.485).However,compared with cases of gastric cancer patients,symptomatic patients are more likely to be smokers and drinkers.(3)The study found that subjects with rs2294008 CT/TT genotypes were among the young(OR = 1.40,95% CI = 1.00-1.94,P = 0.049)and male(OR = 1.39,95% CI = 1.06-1.84,P = 0.019)increased risk of stomach cancer,never smoked(OR = 1.43,95% CI = 1.03-1.97,P=0.031),constant drinkers(OR = 1.60,95% CI = 1.01-2.55,P =0.048),and subjects with non-Kadia tumor sites(OR = 1.43,95% CI = 1.11-1.85,P=0.006).(4)The relationship between rs2976392 and m RNA and rs2294008 and m RNA expression was found to be the same 2.The inhibitory effect of oxaliplatin + 5-fluorouracil on gastric cancer cell line MGC-803 and the drug-drug interaction(1)Oxaliplatin,5-fluorouracil and oxaliplatin + 5-fluorouracil are more sensitive to the inhibitory effect of MGC-803 cells,while the combination of oxaliplatin + 5-fluorouracil has the the most sensitive inhibitory effect on MGC-803 cells.(2)The clone formation rate in MGC-803 cells decreased with the treatment of oxaliplatin,5-fluorouracil and oxaliplatin + 5-fluorouracil,and the combined treatment of oxaliplatin + 5-fluorouracil inhibited the effect is more significant.(3)With Annexin V/PI double staining the apoptotic rate in MGC-803 cells increased with the treatment of oxaliplatin,5-fluorouracil,and oxaliplatin + 5-fluorouracil,while the combined treatment of oxaliplatin + 5-fluorouracil the effect of promoting apoptosis is more significant.(4)Oxaliplatin,5-fluorouracil,and oxaliplatin+5-fluorouracil treatment of MGC-803 cells significantly reduced cells in G1 and S phases,and significantly increased cells in G2/M phase,lead to cell cycle G1 blocking phenomenon;The combined effect of oxaliplatin + 5-fluorouracil was more significant. (5)With DAPI staining the apoptotic rate in MGC-803 cells increased with the treatment of oxaliplatin,5-fluorouracil,and oxaliplatin + 5-fluorouracil;and the combined treatment of oxaliplatin + 5-fluorouracil increased more Significantly.(6)Compared with the Control Group of HGSMC,the expression of PSCA protein in MGC-803 gastric cancer cells was significantly decreased,suggesting that the expression of PSCA may be negatively correlated with the proliferation of gastric cancer cells.(7)After treatment with oxaliplatin,5-fluorouracil and oxaliplatin + 5-fluorouracil for 24 h,the intracellular Bcl-2,VEGF,NF-?B and PSCA m RNA also decreased significantly,and oxaliplatin + 5-Fluorouracil combination treatment is more obvious.(8)Oxaliplatin,5-fluorouracil,and oxaliplatin+5-fluorouracil treatment for 24 h significantly inhibited the expression of Bcl-2,VEGF,NF-?B and PSCA proteins in the cells;and oxaliplatin +5-Fluorouracil combination medication has more significant effects.3.Observation of the efficacy of intraperitoneal hyperthermic perfusion chemotherapy in combination with oxaliplatin + 5-Fluorouracil to treat peritoneal carcinoma of stomach cancer with PSCA(1)Among the 45 cases in the IHPC group,there were 9 PR(20%),19CR(42.2%),7SD(15.6%),and 10 PD(22.2%).The effective(CR+PR)rate of poorly differentiated adenocarcinoma was 52.1%(12 /23),moderately differentiated adenocarcinoma was 61.5(8/13),and symbolic circular cell carcinoma was 44.4%(4/9).Total efficiency(CR-PR)is 53.3%(24/45).Of the 45 cases in the control group,15 were CR(33.3%),10 were PR(22.2%),8 were SD(17.8%)and 12 were PD(26.7%).The effective(CR+PR)rate of poorly differentiated adenocarcinoma was 44.4%(1227).Moderately differentiated adenocarcinoma was 60.0%(6/10),and symbolic circular cell carcinoma was 12.5%(1/8).The total effective rate(CR+PR)is 42.2%(19/45).(2)The study found that in the IHPC group,9 cases improved significantly,16 cases improved,12 stable cases and 8 progressive cases.The KPS effective(improved-stabilized)rate was 82.2%(37/45).The control group improved significantly by 7 cases,14 cases by 14 cases,stabilized by 13 cases and progressed by 11 cases.The effective(improvement + stable)rate of KPS was 75.6%(34/45).(3)The most common adverse reaction is abdominal pain.The rate of abdominal pain in both groups was 35.6% and 28.9%,respectively,of which mild pain was the main one,which could be relieved by the patients themselves after treatment.Three patients had a significant reduction in peripheral blood leukocytes(6.7%)in the IHPC group and one patient(2.2%)in the control group.They dropped from the normal value to 2.68×109/L,2.44×109/L and 2.59×109/L,respectively,and the number of white blood cells returned to normal when G-CSF was used.Hemoglobin reduction and hem cerebellar pain reduction occurred in 4 cases(8.9%)and 7 cases(15.6%),4 cases(8.9%)and 2 cases(4.5%),respectively in two groups of patients.There was no statistically significant difference in liver and kidney function between the two groups before surgery.In addition,the differences in ALT and TBIL levels between the two groups of patients were not statistically significant(p=0.135,p=0.097).However,creatinine and urea nitrogen levels in the IHPC group were significantly higher than in the control group(p=0.016,p=0.010).In most cases,first-degree fever,nausea,and vomiting occur,which improve after treatment of symptoms.The patient had no bleeding,diarrhea,hematuria,allergies,skin rash,blockage or shedding of the perfusion catheter,severe infection of the incision or abdominal cavity in the patient's endometrial hyperthermic perfusion.In the two groups of patients after surgery,there were 1 patient(2.2%)and 3 patients(6.7%)with complicated postoperative lung infections,no patient(0%)and 1 patient(2.2%)with reflux esophagus the inflammation was complicated,with 2 patients(4.4%)and 1 patient(2.1%)with complicated intestinal obstruction,and 1 patient(2.1%)and no patient(0%)with complicated deep vein thrombosis.The difference between the two groups of postoperative complications was not statistically significant.(4)The median follow-up time of the IHPC group was 19 months,and that of the control group was 13 months.In the follow-up process,in the IHPC group,10 patients died,the overall survival rate was 17.8%(8/45),and progression-free survival rate was 66.7%(30/45).In the control group,21 patients died,the overall survival rate was 13.3%(6/45),and progression-free survival rate was 42.2%(19/45).Conclusion:(1)In summary of our findings,in view of this,we conducted a case-control study to investigate the relationship between the PSCA gene rs2294008 C> T and rs2976392 G> A polymorphisms and the risk of gastric cancer in the Chinese population.Two PSCA genes rs2294008 > T and rs2976392 > A polymorphism were shown to be significantly associated with an increased risk of stomach cancer in the Chinese group.(2)Oxaliplatin,5-fluorouracil and oxaliplatin+5-fluorouracil have inhibitory effects on the proliferation and cell cloning ability of MGC-803 and HGSMC cells,and they are concentration-dependent.The apoptotic rate and cell cycle arrest in MGC-803 cells increased with the treatment of oxaliplatin,5-fluorouracil,and oxaliplatin + 5-fluorouracil.The combination of oxaliplatin + 5-fluorouracil was used.Treatment of this effect is more significant.Compared with the Control Group of HGSMC,the expression of PSCA protein in MGC-803 gastric cancer cells was significantly decreased,suggesting that the expression of PSCA may be negatively correlated with the proliferation of gastric cancer cells.After treatment with oxaliplatin,5-fluorouracil and oxaliplatin +5-fluorouracil for 24 h,the intracellular Bcl-2,VEGF,NF-?B and PSCA m RNA and protein were also significantly reduced,and oxaliplatin+5-Fluorouracil combination treatment is more obvious.(3)In summary,IHPC and oxaliplatin + 5-fluorouracil was performed in gastric cancer with peritoneal metastasis patients of PSCA population has a certain therapeutic effect on gastric cancer.In addition,the patients showed better tolerance,and their OS and PFS were significantly better than those in the control group. |
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