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Establishment Of A Clear-cell Renal Cancer Cell Tumor Xenograft Model By Using Patient-derived Cells To Examiningt Cell Sensitivity To Molecular-targeting Agents

Posted on:2021-05-03Degree:MasterType:Thesis
Country:ChinaCandidate:Y WeiFull Text:PDF
GTID:2404330611993797Subject:Surgery
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Background:Renal cancer is a common urinary system tumor.The most important pathological type is renal cell carcinoma(RCC),which accounts for more than 90% of the total number of patients with renal cancer.RCC can be further subdivided,in which clear renal cell carcinoma(ccRCC)is the main pathological type of RCC,accounting for more than 85% of the total incidence of RCC.At present,surgical resection is still a single lesion such as primary renal cancer,as long as the treatment prognosis is good,but patients with multiple,diffuse renal cancer,and renal cancer recurrence are difficult to receive surgical contact treatment,the overall prognosis of patients is still better difference.For patients with renal cancer who are not suitable for surgery,molecular targeted therapy(taking various oral small molecule protein kinase inhibitors)is its primary therapeutic strategy.At present,molecular targeted drugs including Sorafenib and Sunitinib have been widely used in the clinical diagnosis and treatment of renal cancer,bringing good news to patients.Despite this,there are still many problems in molecular targeted therapy of renal cancer:(1)There are individual differences among different patients in molecular targeted therapy of renal cancer,and there is no clear indicator molecule for molecular prognosis in the treatment of renal cancer patients;2)There is drug-resistance phenomenon in molecular targeted therapy of renal cancer;(3)Molecular targeted therapy is expensive,and if there is a reliable method to test the effect of patients receiving molecular targeted therapy,Differentiating helps to alleviate the financial burden on patients.Therefore,researching and establishing relevant research models and research methods,predicting the sensitivity of patients to molecularly targeted drugs,and helping to achieve more effective molecular targeted therapy have important theoretical and practical significance.Aims: The aim of this study was to examine the sensitivity of patients-derived ccRCC(clear cell renal carcinoma)cells to molecularly targeted drugs using patient-derived tumor xenograft models(PDX models)using patient-derived cells(PDCs).Sexuality provides theoretical and experimental basis for clinical diagnosis and treatment.Methods:The PDCs of ccRCC were subcutaneously inoculated into nude mice to establish a tumor model,based on which the molecularly targeting drugs Sunitinib,Sorafenib,Lenvatinib,Regorafenib were orally administered to examine the inhibitory effect of the drug on the subcutaneous formation of ccRCC PDCs in nude mice.At the same time,samples of the cell and tumor tissue were analyzed by qPCR technology.The targets of the above-mentioned molecular targeting drugs(receptor tyrosine protein kinase such as VEGFR and protein kinase of MAPK signaling pathway such as ERK and AKT)was examined.Results:The results showed that five lines of ccRCC PDCs were successfully obtained and nude mice were injected with ccRCC PDCs to obtain a subcutaneous tumor model of kidney cancer in nude mice.During the process of culturing PDCs cells in vitro,the expression of target molecules of molecular targeting agents decreased.Moreover,the expansion of these molecules in tumor tissues is relatively stable.The inhibitory rates of molecular targeting agents were individual differences among the selected molecular targeted drugs,and Lenvatinib's anti-tumor activity is stronger than several other molecular targeted drugs.Conclusion:The results indicate that using the patient-derived clear cell renal cancer cell line successfully established an animal model of kidney cancer and tested the sensitivity of renal cancer cells to molecular targeted drugs,which can provide rational and experimental basis for relevant clinical diagnosis and treatment.?...
Keywords/Search Tags:ccRCC, molecular targeting agents, PDCs and PDXs, drug sensitivity testing
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