| Purpose:(1)Through injection VX-2cells suspensions build a peritoneal carcinomatosisfrom gastric cancer animal model,then used cisplatin、endostatin、PA-MSHA injectionintraperitoneal hyperthermia perfusion chemotherapy on the animal model in differentgroups authenticate the safety and analyse curative effect of above-mentionedmedicine in CCHIPC.(2)Through determinating the expression of the VEGF、PCNA in the deadspecimen of the all VX-2rabbits model on peritoneal carcinomatosis from gastriccancer in different groups by immunohistochemistry, we explore the possible cancerinhibition mechanism of Cisplatin、 Endostatin、 PA-MSHA injection used inintraperitoneal hyperthermia perfusion chemotherapy on the animal model.Methods:(1)Selected36New Zealand white rabbits,the injected VX-2cells suspensionsbuild a peritoneal carcinomatosis from gastric cancer animal model. Observingchanges of the weight and appetite of them everyday.At the8th day after the buildingthe animal model,determining blood routine、 hepatic and renal function andelectrolyte of the rabbits。(2)In the9th day after builded animl model,we make exploratory laparotomy toscoring the ePCI of the rabbits. The selected36rabbits were divided into six groupsrandomly, six rabbits in every group. Six groups were A group which used the usedcisplatin and endostatin make CCHIPC therapy, B group which used the usedendostatin make CCHIPC therapy,C group which used the used cisplatin makeCCHIPC therapy,D group which used the used PA-MSHA make CCHIPC therapy,E group which used the used cisplatin、endostatin and PA-MSHA make CCHIPCtherapy,F group(the negative control group) didn’t make CCHIPC therapy after mademodel.The third day after the first CCHIPC therapy,the treatment groups repeated theCHIPC therapy. Determining blood routine、hepatic and renal function and electrolyteof them1day before and4days after the CCHIPC therapy.Observing changes of theweight and appetite and noting the adverse event and survival days of them.Takinggeneral observation of peritoneal carcinomatosis in the dead specimen with or withoutascites,then score the ePCI and the abdominal adhesions of them.After abovemeasures, HE staining、determinating the expression of the VEGF、PCNA byimmunohistochemistry were used.If the dead specimen with ascites, pathologicaldetection of the exfoliated cells were used. Statistic analysis was applied to determinethe difference between the six groups at last.Results:(1)Blood routine、hepatic and renal function and electrolyte of them1day beforeand4days after the CCHIPC therapy of all groups had no statistical difference (P>0.05).(2) Fewer adverse events and complications occurred in all groups.There was arabbit dead in E group(cisplatin、 endostatin combined PA-MSHA injection inCCHIPC)because of chronic diarrhea. It was found that3(A group which usedcisplatin combined endostatin in CCHIPC)、2(C group which used cisplatin inCCHIPC)、3(E group which used cisplatin、endostatin combined PA-MSHA injectionin CCHIPC)rabbits had symptom of diarrhea. They were cured by using antibioticswithin1week.(3) Survival days of all the groups: A group was36.33±3.72days, B group was31.17±3.66days,C group was32.00±3.58days, D group was30.80±4.71days, Egroup was37.50±7.34days, F group was25.17±2.93days. Significant difference werefound between therapy groups(A、B、C、D、Egroup) with negative control group(Fgroup),P＜0.05. Significant difference were found among A group which usedcisplatin combined endostatin in CCHIPC、B group which only used endostatin in CCHIPC、C group which only used cisplatin in CCHIPC negative control group(Fgroup),P=0.033,0.044. There was no statistical difference among the single medicineused in CCHIPC group(A、B、Cgroup),P＜0.05. There was no statistical differenceeither between E group (cisplatin、endostatin combined PA-MSHA injection used inCCHIPC) and A group(cisplatin combined endostatin used in CCHIPC),P＜0.05.(4)Anatomy of the death specimens in negative control group(F group) had thetypical characteristics of peritoneal carcinomatosis from gastric cancer similar tohuman extensive abdominal metastasis from gastric cancer.Compared with those othergroups, Abdominal metastasis of E group (cisplatin、endostatin combined PA-MSHAinjection used in CCHIPC) was most mild. Liver metastasis of the groups which usedendostatin (A、B、Egroup) are less.The Anatomy of the death specimens those othergroups were simliar with negative control group.(5)Scores ePCI of the death specimens: The ePCI scores of F group was18.00±1.55,which was the highest. The ePCI scores of E group was12.00±1.79,which wasthe lowest. Significant difference were found between the ePCI scores of negativecontrol group(F group) with therapy groups(A、B、C、D、Egroup),P=0.020,0.003,0.002,0.000,0.000. Significant difference were found between the ePCI scores of Egroup(cisplatin、endostatin combined PA-MSHA injection used in CCHIPC group)withA、B、C、D、Fgroup,P=0.000,0.001,0.002,0.020,0.000. There was no statisticaldifference among pairwise comparison of those other groups.(6) Scores the abdominal adhesions of the death specimens: The abdominaladhesions scores of F group was3.67±0.52,which was the highest. The abdominaladhesions scores of E group was1.17±0.75,which was the lowest. Significantdifference were found between the abdominal adhesions scores of negative controlgroup(F group) with therapy groups(A、B、C、D、Egroup),P=0.000,0.000,0.000,0.001,0.000. Significant difference were found between the ePCI scores of E group(cisplatin、endostatin combined PA-MSHA injection used in CCHIPC group) withB、C、D、Fgroup,P=0.004,0.001,0.000,0.000. There was no statistical difference amongpairwise comparison of those other groups.(7)Significant difference were found between the gray value of VEGF expression in pairwise comparison of all groups, P＜0.05. The gray value of VEGF expression ofF group was77.33±6.77,which was the lowest. It suggested that The VEGFexpression of F group was highest. The gray value of VEGF expression of Egroup was200.17±4.26,which was the highest. It suggested that The VEGFexpression of E group was lowest. Significant difference were found between the grayvalue of PCNA expression in pairwise com-parison of all groups, P＜0.05. The thegray value of PCNA expression of F group was83.33±3.49,which was the lowest. Itsuggested that The PCNA expression of F group was highest. The gray value ofPCNA expression of E group was184.83±3.76,which was the highest. It suggestedthat The PCNA expression of E group was lowest.Conclusion:(1)This experiment used injection VX-2cells suspensions method to build aperitoneal carcinomatosis from gastric cancer animal model.The animal model weresteady and had long survival time. So we consider that this animal model couldprovide the steady basement of the experimental study for diagnosis and treatment ofperitoneal carcinomatosis from gastric cancer.(2) CCHIPC is a safe method to treat malignant tumor. It not only kills tumors toprolong life but it also decreases the abdominal adhesions to improve the quality oflife.(3) Cisplatin、Rh-Endostatin and PA-MSHA injection had a synergistic effect onCCHIPC therapy. We presume that the medicine for CCHIPC down-regulated theexpression of VEGF and PCNA,then blocked the implantation metastasis of tumorcell. The concrete mechanism needs further research. |
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