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Experimental Study And Clinical Application Of Tumor Ultrasonic Heat Therapy

Posted on:2004-02-20Degree:DoctorType:Dissertation
Country:ChinaCandidate:H ZhaoFull Text:PDF
GTID:1104360122455192Subject:Surgery
Abstract/Summary:PDF Full Text Request
According to the predication of WHO,malignant tumor will be the first killer to human health in the 21th Century. As far as the actual condition is concerned, any single conventional cancer treatment available (resection,chemotherapy or radiotherapy) can hardly be a radical therapy to the patient with malignant tumor, especially those with middle or late stage ones on admission. Heat treatment for cancer can induce the death of cancer cells, and Multi-unit Array Ultrasound Hyperthermia System,which has been developed in the past 2 decades, is able to heat deep-seated tumor by taking advantage of ultrasound in its great penetration ,satisfactory efficacy of temperature elevation and good orientation ,and has been known as an effective approach to tumor treatment ; High Intensity Focused Ultrasound(HIFU) , a more advanced technique developed rapidly in the later years, can bring beams of ultrasound to a tight focus within deep-seated tumor tissue and produce rapid and intense heating effect causing prompt tissue ablation (coagulation necrosis )in 0.1-0.5second ,whereas the intervening tissues within the beam path and the surrounding normal tissues remain intact. As an effective and noninvasive local palliative therapy for tumors, HIFU begin to receive much attention in the cancer thermotherapy field. This study investigate both the different local effect of ultrasound treatment in different thermal dose on tumors and its cancer ablation mechanism ,with the investigation the effect of HIFU treatment on systemic anti-neoplastic immunity.This study showed a significant decrease of tumor volume in LC liver cancer bearing nude mice as compared with control group on the 19th day after treated with Multi-unit Array Ultrasound Hyperthermia System in curative thermal dose(42.5℃× 30min×5times ),the tumor growth inhibition rate was 91%,the density of apoptotic cell in treated group was markedly higher and the expression rate of PCNA was reduced. If the tumor model was irradiated in lower thermal dose(41℃×12min×5times),the tumor volume was greater than that of control group on the 19th day. Several groups of H22 liver cancer bearing KM mice were treated with HIFU and sacrified about 2 weeks after treatment , coagulation necrosis of cancer cells developed in the irradiated zone ,and it was also found that the growth of tumor on the contralateral side was inhibited as well as the cytotoxic activity of spleen lymphocyte to H22 cells raised ,if the irradiated region coverd whole tumor, the tumor volume was decreased significantly as compared with control group, the tumor growth inhibition rate was 82%,HIFU treatment which covered only one third of the total tumor seemed to accelerate the growth of local tumor ,however ,repeated irradiation covered partial area of tumor with HIFU revealed similar result as those single irradiation to cover whole tumor. This study also showed that HIFU therapy could reverse the changes of cytokine pattern from Th1 to Th2 in H22 cancer bearing KM mice. Using ELISA, serum levels of IL-2,IL-4,IL-10 and IFN-γwere examined ,as a result, the concentration of IL-2 and IFN-γin HIFU treated group were significantly higher than that of control group ,on the contrary ,the IL-4 and IL-10 level were lower compared with control group. Another study with flow cytometry showed that HIFU treatment caused a obvious increase in the percentage of γδT cell ,which has been known as non-MHC-restricted cytotoxic lymphocyte and has a anti-neoplastic capacity of broad-spectrum.In the HIFU clinical application, we first investigated the satety and effect of HIFU therapy in breast cancer patient, for irradiating superficial tumor is comparatively safe and its effect could be easily investigated. Eighteen patients with breast cancer from Ⅱ to Ⅲ stage were treated with HIFU 2 weeks before radical mastectomy and lymphocytes in peripheral blood were isolated and lymphocyte subsets were compared pre and post HIFU treatment by flow cytometry. Pathological examination confirmed coagul...
Keywords/Search Tags:HIFU, hyperthermia, Apoptosis, PCNA, Th1 /Th2, γδT cell, breast cancer, CD4+/CD8+, thermal dosage, Multi-unit Array Ultrasound Hyperthermia System
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