The Prevention And Treatment Role Of JianPi YiShen & JieDu Therapy On The Recurrence And Metastasis Of Gastric Cancer And The Regulation Mechanism Of It On The Apoptosis Signal Conduction

Gastric cancer is one of the common malignant tumors which threaten the life and health in our country. The postoperative recurrence and metastasis is an important factor that endangers seriously the life. How to decrease or avoid the recurrence and metastasis, and improve the quality of life, and prolong the life span, which is currently the most imminent topic on the research domain of gastric cancer. Advisor Sun Gui-zhi is one of the distinguished experts who are active on the oncoma forefront of combination of TCM with Western medicine. She has a unique approach on treating the oncoma of digestive system, especially being expert in gastric cancer. In recent 40 years, the tumor patients who she treated have reached more than 500 thousands. On the basis of combing a great deal of the ancient TCM literature relating to gastric cancer and tumor metastasis, advisor's clinical experience of the prevention and treatment gastric cancer were digged thoroughly by the modern scientific theory and technology. Meanwhile, the recurrence and metastasis of the 615 murine with forestomach carcinoma (FC) afer amputation (AMP) was adopted as animal model. And the techniques which flow cytometry (FCM), TUNEL, AV-PI, Realtime RT-PCR, immunohistochemistry (IHC) were applied to detect the lab indexes. From the different layers of whole—cell—gene and molecule—signal conduction etc., to explore extremely the molecular mechanism of JianPi YiShen & JieDu therapy prevented and treated the postoperative recurrence and metastasis of gastric cancer. From one aspect, the reach brought to light the scientific content of which were the theories of TCM and the clinical experience of the renowned expert.Part I : Theoretical studies1. The ancient TCM literature has the far-reaching historical significance on TCMtherapeutics of gastric cancer and tumor metastasis.On the basis of combing a great deal of the ancient TCM literature relating to gastric cancer and tumor metastasis, the recognition of TCM on such species disease and syndrome was divide into five period: (1) It was the sprouting period that before the Spring & Autumn Period and Warring States Period. (2) It was the initial form period that from the Spring & Autumn Period and Warring States Period to the late years of the Eastern Han Dynasty. (3) It was the investigation and development period that the Jin, Sui and Tang Dynasties. (4) It was the substantial period that from the Song Dynasty to the Jin and Yuan Dynasties. (5) It was the system and initial consummate period that the Ming and Qing Dynasties.2. Academic experience of advisor on the prevention and treatment the postoperative recurrence and metastasis of gastric cancerAccording to therapeutic principles of "concentrating treatment on the root cause" and "strengthening healthy Qi and eliminating pathogenic factors", and to combine together the syndrome characteristic of "deficiency of root and excess of branch" of which gastric cancer postoperative patients. (1) To advocate major therapeutic method mainly to JianPi YiShen & JieDu therapy. This therapy means to strengthen healthy qi and to eliminate pathogenic factors simultaneously. (2) The diagnose takes differentiation of disease as first, and the treatment regard differentiation of syndrome as principal. (3) To raise the principle of prevention and the principle of treatment were laid equally stress on. Through a long period of taking medicine, the curative effect was consolidated. (4) At the same time, to emphasize the importance of adjusting the food and the mental state.Part II: Clinical studies1. The clinical study of medicine and syndrome on advisor's prevention and treatment the recurrence and metastasis of gastric cancerTo make use of the bioinformation data mining (DM), and to take advisor's prescription and medicine as the clues, 351 pieces of the primitive prescription were carried out to analyze from multi-angles. Regularities were summarized as follow: (1) Gastric cancer was divided into six basic syndromes by Syndrome differentiation and treatment. Six elementary formulae were used commonly and respectively. They were "Decoction of four Noble Drugs", "Minor Decoction of Relieving Stuffiness in the Chest", "Pulse-activating Powder and Gypsum Decoction", "Tangerine Peel and Bamboo shaving Decoction", "Decoction of Three Kinds of Kernels", and"Bupleurum Powder for Relieving Liver-Qi". (2) There are 214 pieces of drug in all prescriptions. According to frequency distribution, to sum up 23 pieces of drug were used the most frequently. (3) According to the drug property theory of traditional Chinese medicine, the majority drug properties were the warm and the neutral in nature. In addition to, bitter cold drug were second. (4) According to functional classification of drugs, it was the first place that a kind of the tonification drug in 61 pieces of drug which were seen the most frequently. It was the second place that a kind of the drug for heat-clearing and detoxicating and a kind of the drug for invigorating blood circulation and eliminating stasis and a kind of the drug for regulating QI flow. (5) It is the quintessence of medication that the use of a couple of drugs. (6) Not only syndrome differentiation and treatment based on TCM theory but also treatment based on differentiation of disease, furthermore, to integrate the progress of TCM on modern pharmacology research, the advisor pay attention to the multitude effects of a drug in clinical practice.2. Influence of JianPi YiShen & JieDu therapy on the quality of life(QOL) in postoperative patients of the progression gastric cancerThe study aim was to assess of the clinical efficacy of treatment for JianPi YiShen & JieDu therapy and its effect on QOL in postoperative patients of the progression gastric cancer. EORTC QLQ—C30(Chinese version 3.0) is a developed questionnaire, which was adopted to assess the effect of which prior-treatment and post-treatment of QOL in postoperative patients of the progression gastric cancer. 46 patients who had been treated for three to six months were investigated. The questionnaire consists of seven functioning scales (physical, role, emotional, cognitive, social, symptom and financial impact), and the global quality of life scale. Improvement of QOL was not only the global quality of life scale but also multi-functioning scales, and especially there were the significant improvement on several scales of physical, role, emotional, social and symptom. Furthermore, by principal component analysis (PCA), above several scales belong to the first principal component of the questionnaire. The study showed postoperative patients of the progression gastric cancer must gain profit from long-term TCM treatment of JianPi YiShen & JieDu therapy. Chinese medicine therapy was essential in an ideal project of combined therapy of cancerPart HI: Experimental studies1. To establish a patient-like animal models of the recurrence and metastasis ofthe 615 murine with FC afer AMP.2. JianPi YiShen & JieDu Formula (JYJF) could inhibit the regional recurrence and pulmonary metastasis (PM) of the 615 murine with FC afer AMP(recurrence tumor inhibition ratio is 63.11% and PM inhibition ratio is 27.8%). The level of recurrence and metastasis were controlled obviously, and QOL was raised and life span was prolonged (life prolong ratio is 94.44%).3. By the application of different testing apoptosis methods, it was confirmed that the key mechanism of action on JYJF which of the prevention and treatment postoperative recurrence and metastasis of gastric cancer which is to alter the apoptotic sensitivity of both T lymphocytes and tumor cells.4. Through to elevate T lymphocytic reproductive activity, JYJF can degrade T lymphocytic apoptotic activity. The Fas expression in T lymphocyte was lower, and the FasL expression in which was elevated. Thereby, JYJF can sublimate immunization surveillance capability and reduce tumour cell immune escape. The analysis of proliferation and apoptosis of T lymphocyte might play an important role on overall assessment cellular immunity of organism.5. Signal conduction disturbance of apoptosis that is one of key mechanisms of the recurrence and metastasis of tumor. JYJF induced apoptosis involved in Fas death receptor -mediated apoptotic pathway and mitochondria-mediated apoptotic pathway. JYJF induced effector caspase-3 activation and apoptosis through coaction of both apoptotic pathways.6. The possible molecular mechanism of JYJF involved in that the expression levels of Fas protein and its mRNA of tumor tissue were increased, and the expression levels of FasL protein and its mRNA were decreased, accordingly up-regulated initiator caspase-8 activation. Meanwhile, the expression levels of Bax protein and its mRNA were increased, and the ratio of Bcl-2/Bax was decreased, accordingly the expression levels of Bcl-2 protein and its mRNA were attenuated and apoptosis was inhibited. In addition to, it was observed that both the mitochondria membrane potential (Av|/m) of tumor cell and PH value of inside cell were decreased. Mitochondria-mediated apoptotic pathway enlarged efficiently apoptotic signal. These increased an experiment basis for multi-target point effect of compound recipe on TCM.