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Yang Wei Kang Liu Granules On The Prognosis Of Advanced Gastric Cancer And It Mechanisms Of Apoptosis Induced

Posted on:2011-03-31Degree:DoctorType:Dissertation
Country:ChinaCandidate:L L HeFull Text:PDF
GTID:1114360305990172Subject:Traditional Chinese Medicine
Abstract/Summary:PDF Full Text Request
Gastric carcinoma is one kind of common malignant tumor that can do serious harm to human health. As the postoperative recurrence and metastasis are major cause of death in most clinical patients, so people have been seeking treatment other than surgical method of gastric cancer to extend survival of patients. Professor Sun Gui-zhi has engaged in treating some kind of malignant tumors with methods of Integrative Medicine for 40 years. She has rich experience of treating gastrointestinal cancers, especially gastric cancer, and gets a significant effect. Yang Wei Granules (YWKL) was developed by Professor Sun Gui-zhi for treating advanced gastric cancer. Its rule is increasing Qi and providing nutrition for stomach, spleen and kidney, and promoting blood circulation, detoxify and anti-cancer. Clinically applied for 20 years, it has been proved playing a role of preventing of tumor recurrence, metastasis and prolonging survival in patients with gastric carcinoma. This thesis summarized Professor Sun Gui-zhi's experience of treating gastric carcinomas from theory, method, prescription and drugs on the basis of research in the past several years. We use modern technology to conduct experimental research and want to explore the active ingredients of those Chinese medicines to improve the clinical efficacy. The carcinoma model is 615 mice of recurrence and metastasis after surgical method of treating gastric cancer. The molecular mechanisms of inducing apoptosis and the role of improving symptoms and prolonging life of YWKL are researched by methods of immunohistochemistry (IHC), Realtime RT-PCR, AV-PI, flow cytometry, TUNEL and other techniques from the whole-cell-gene-signal transduction level. And the scientific contents of rational Fuzheng and Quxie are revealed from those sides.1 Theory researchBased on the research in the past, I summarized the experience of Professor Sun Guizhi's treating gastic cancer from four sides, such as the principles, methods, prescriptions, and chinese traditional medicines, to explore the material basis of the clinical effect.1.1 Understanding of the pathogenesis of gastric cancerNo records of gastric cancer that we can find in traditional Chinese medicine theory. But we can see some descriptions of stomach syndrome and symptoms those are similar with gastric cancer, such as "stomachache", "Ye Ge", "Epigastric Distension", "wei fan". Professor Sun Guizhi summarized the relevant ancient and contemporary medical practices on cancer etiology, pathogenesis of knowledge, blent with her clinical experiences for more than 40 years, indicated that the spleen deficiency as the most important aspect of gastric cancer, and that a variety of causes can damage spleen's and stomach's physical function, then the focus Yong Zhi, food product, so, qi stagnation, Yongzhi of heat stored up health drugs, eventually developed into gastric cancer.1.2 therapeutical principleFor her long-term clinical expierince, Professor Sun Gui-zhi has summarized some important principles, such as combinating people's symptoms with pathology report as the basis of diagnose, paying more attention to the role of human' body itself, considering spleen and kidney as the center of human' health, and the role of physical and mental adjust, the role of coordinating internal and external factors, righting evil spirits, insist on defending side to "protracted war" against cancer and its recurrence and metastasis. Common treatment methods include that adjusting spleen and stomach' function and promoting digestion, removing the damaged inssue and promoting the new inssue growwing, and anti-cancer detoxification. Those methods used together in the inhibition of tumor recurrence and metastasis, stability, and shrinking the tumor, improving quality of life and prolonging survival to achieve impressive results. 1.3 commonly used formulaProfessor Sun Gui-zhi usually use some experienced prescriptions which we called "Little Standard prescriptions", such as "Tenghu soup" which consists of Actinidia arguta and Polygonum, "Puhuang-Baizhi-Fengfang soup" which consists of Typhae, Angelica, Lucy hives, and Hair Carbon, "Jin-Mai-Daizhe soup" which consists of Gallus gallus, the Health and malt, Ruddle.2 clinical researchYWKL is an exprimental prescription for Professor Sun Gui-zhi treating advanced gastric cancer which was developed by the principles of adjusting Qi and Stomach, spleen and kidney, promoting blood circulation and detoxification.Objective:Explore the role of YWKL Modified Differential Treatment in affecting patients' survival and quality of life with advanced gastric cancer by non-randomized concurrent control studies on 258 cases of advanced gastric cancer. Methods:A retrospective control study period, included a total of 258 cases of advanced gastric cancer (147 cases of Integrated Traditional and Western group, chemotherapy group 111 cases), chemotherapy in both groups (post-entry group to fluorouracil-based programs chemotherapy, and according to type of cell pathology, physical condition, etc. can be combined use of platinum, anthracycline or taxol, the general treatment of 3-6 cycles) and other medical therapy; Integrative Medicine Group at this based on the use YWKL. Differentiations are be took on once every two weeks, and the basic prescriptions are amended correspondingly. And we record the duration of medication. For a long term we follow up those patiants. And the final data are managed by software EPidata3.1 to estimate the median survival time using Kaplan-Meier method. Finally we use SPSS 17.0 statistical software for statistical analysis. Results:Comparison of one, three, five-year survival rate, those of Integrative Medicine Group are 98.6%,84.4% and 68.7%, respectively the chemotherapy group are 72.1%,12.6%,5.4%. Median survival time of Integrative Group is 72.69 months, and in chemotherapy group it's 21.94 months, they have statistically significant by statistical analysis (P<0.05). KPS score changes before and after treatment, Integrative Medicine Group are increasing 62.6%, stably 32.6%, declining 4.7%, those of chemotherapy group are increasing 27.9%, stably 59.4%, declining 12.6% respectively. Evaluation of weight changes before and after treatment, Integrative Medicine Group are increasing 53.1%, stably 39.5%, declining 7.5%, and those of chemotherapy group are increasing 44.1%, stably 25.2%, declining 30.6%. Changes of KPS score and weight before and after treatment were significant statistically (P<0.05). Conclusion:YWKL-based differentiation in treatment of advanced gastric cancer patients prolonged their survival, improved the quality of life of patients. The role of TCM treatment in improving the overall prognosis of gastric cancer deserves more randomized controlled studies to explore.3 exprimental researchUsing 615 mouse models with gastric cancer recurrence and metastasis and human cancer cell lines MGC803, BGC823 Anoikis and multicellular spheroid model as the carrier, using flow cytometry FCM, TUNEL, AV-PI, Realtime RT-PCR, MTT, immunohistochemistry and other methods of experimental techniques, from the whole-cell-gene-the signal transduction level, we deply improve the molecular mechanism of the YWKL against tumor and promoting the overall prognosis of gastric cancer, and reveal the scientific content of the principle of attaching equal balance to extend the treatment of advanced gastric cancer survival.3.1 animal experiments3.1.1 Successfully established mouse 615 models which are similar to clinical metastasis and recurrence of gastric cancer for dynamic observation of recurrence and metastasis. It is a foundation foe us to research the mechanism of recurrence and metastasis of the action of gastric cancer.3.1.2 Chinese compound herb YWKL has some inhibitory effects on carcinoma in 615 mice for the postoperative local recurrence and distant metastasis (inhibition rate of tumor recurrence and lung metastasis are 68.07% and 33.33%), and decreases the degree of tumor recurrence and metastasis, and improve the quality of life and prolong survival (100% extension of life).3.1.3 Using different methods to detect apoptosis of gastric cancer cell and confirming that the change of apoptosis sensitivity of gastric cancer cell is an important control mechanism of YWKL for recurrence and metastasis.3.1.4 Chinese compound herbal YWKL can inhibit telomerase proliferation by promoting mitochondrial to release Cytc and activate Caspase cascade and enhance the expression of pro-apoptotic protein Smac and Apaf-1 protein, and reduce the expression of apoptosis inhibitory protein XIAP. By detecting both proliferation and apoptosis of telomerase in tumor cells, we dissus the telomerase's effect on apoptosis, to provide new ideas and scientific theory for rational application of Traditional Chinese Medicine for decreasing recurrence and metastasis.3.2 cell experiment3.2.1 Successful replicate human gastric cancer cell line MGC803, BGC823 Anoikis, and multicellular spheroid model, which are fit for imitating those gastric tumor cells with metastasis in vivo state, in order to provide a reliable technology platform to verify the YWKL's role and the mechanism of anti-metastasisr.3.2.2 Using the method of serum pharmacology prepared containing YWKL serum by orthogonal design, and observing the best time of serum screening and the effective blood concentration by MTT method.3.2.3 Disorder of apoptosis signal transduction is one important mechanisms of tumor recurrence and metastasis. Serum of Chinese compound herbal YWKL can enhance the apoptosis sensitivity of human gastric cancer cell line MGC803, BGC823 and activate Caspase-3 to induce apoptosis of tumor cells by regulating mitochondrial pathway.
Keywords/Search Tags:gastric cancer, apoptosis, apoptosis-related genes, recurrence, transfer, treatment of TCM
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