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The Mechanisms Of Improving Cachexic States

Posted on:2003-02-21Degree:DoctorType:Dissertation
Country:ChinaCandidate:X P DuFull Text:PDF
GTID:1104360062490994Subject:Integrative Medicine
Abstract/Summary:PDF Full Text Request
The incidence and death rate of lung cancer in Chinese gradually rose every year. In some metropolis, the incidence of lung cancer had been the first of all diseases. About 70% patients were in terminal as they are diagnosed. It wasn't satisfying that chemotherapy prolonged the life of terminal patients, though the remission rate promoted with the progress of chemotherapeutants. An important reason was that the terminal patient' s sensitivity to treatment depressed so that the treatment deteriorated the patient's constitution. The cachexia, which seriously debased patient's quality of life(QoL) and reduced survival time, occured in 50%~80% patients. It was important to research how to prevent or treat cachexia in terminal non-small-cell lung cancer (NSCLC) patients to prolong the survival time. This study aimed at observing the effect of PingFei Mixture treating cachexia and researching the mechanism of that effect in cytokine level.In the clinical trial, 46 terminal NSCLC patients with cachexia were divided in pairs into two groups, which PingFei Mixture (PingFei,PF) and Medroxyprogesterone Acetate (MPA) were given respectively. The QoL, clinical remission rate, food intake, body weight, the thick of flexion crease, the circumference of upper arm were record and serous pro-albumin, T cell subset, pro-cachetic cytokines such as IL-6 and TNF-α were examined. In the animal experiments, mice with inoculated Lewis pulmonary carcinoma were used as cachetic model. The control group was given Cisplatin and Medroxyprogesterone Acetate. The food intake,body weight, life performance, and the size of tumor were examined. ELASA was used to exam serous IL-6, IL-1α, TNF-α levels while immunohistochemistry (Strept-avidin biotin complex,SABC) was used to exam IL-6, IL-1α, TNF-α, TNFR1 and TNFR2 expressions in the tumor tissue. The correlated analysis between cytokines in serous and in tissue were explored.The results were interesting. PF was similar to MPA in improving patient' s food intake but was prior to MPA in improving QoL. The weight raise rate in PF is 69.57% that was significantly higher than it in the control group. The raise time of serous pro-albumin and albumin of PF patients was anterior to those of MPA, and the raise extent was higher in PF group. There was no difference in the thick of flexion crease of both groups while there was remarkable difference in the circumferences of upper arm. IL-6 and TNF-α were decreased in PF group but in MPA group only IL-6 was decreased. The similar results were observed in the animal experiment. PF reduced mice serous IL-1α as well. It was found that in PF group the expressions of TNFR2 and TNFR1 in tissue increased and the expressions of IL-6, IL-1α, TNF-α decreased. There was correlation between serous and tissue IL-6, IL-1α. The serous TNF-α was positively correlated to TNF-α in tissue and was negatively correlated to tissue TNFR2 and TNFR1 expression.PingFei Mixture was found in clinical trial and animal experiment being able to restrain the tumor developing.The conclusions can be made from those facts: PingFei Mixture, which is constituted under the principle of enriching Yin and clearing lungs, can decrease serous IL-6, TNF-α, IL-1α level and improve the QoL of cachexia patients. The mechanism of PingFei Mixture treating cachexia is complex. As this study suggests, PingFei Mixture reduces TNF-α, IL-6, IL-1α by regularizing cytokine expression; increases TNFR1 and TNFR2 expression in carcinoma tissue to sensitizing tissue to the cytokine; reduces the energy depletion and protein catabolism in muscle and increases protein synthesis in the liver. It is showed that the Traditional Chinese Medicine has superiority in preventing and treating cachexia. The mechanism needs the further studies.
Keywords/Search Tags:cachexia, non-small-cell lung cancer (NSCLC), cytokine, TNF-α, IL-6, clinical trial, experiment, Traditional Chinese Medicine (TCM)
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