Experimental Study And Clinical Application Of Tumor High Intensity Focused Ultrasound Therapy

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 for the patient with malignant tumor, especially those with middle or late stage ones on admission. High Intensity Focused Ultrasound (HIFU), a advanced technique developed rapidly in the later years, by taking advantage of ultrasound in its great penetration, satisfactory efficacy of temperature elevation and good orientation, 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) within 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 investigates both the different local effect of ultrasound treatment in different thermal dose in the vivo and vitro, and its cancer ablation mechanism firstly; we emphasize the investigation with the effect of HIFU treatment on systemic anti-tumor immunity.PartⅠThe Different Effect of Ultrasound Treatment in Different Thermal Dose in the rive and VitroObjective: 1. Approaching the therapeutical effect of HIFU treatment in different thermal dose to 4T1 caner cell in vitro; 2. Observing the therapeutical effect of HIFU treatment in vivo.Methods: Using HIFU with different thermal dose to treat 4Tl cancer cell, calculated the death rate; detected the OD value for 4 days with MTT, evaluated the rate of proliferation; established the model of 4T1 transplanted tumor, investigated the tumor volume and pathological change. Result: The death rate of HIFU in 500W/cm~2, 1000 W/cm~2 and 1500 W/cm~2 were 35.34%, 78.92% and 80.56%; in the animal experiment the tumor growth inhibition rate was 52.22% and 72.27% respectively.Conclusion: HIFU can kill the 4T1 cancer cell and inhibit proliferative ability in vitro; HIFU therapy can inhibit the growth of 4T1 transplanted tumor in vivo.PartⅡThe Anti-tumor Immunity Effect of HIFU Therapy Objective: 1. Approaching the change of immune function after HIFU; 2. Observing the expression of HSP70 in the target zone of tumor after HIFU. Methods: Contrasting the kill capability of splenic lymphocyte between HIFU group and control group; detected the ratio of Th1/Th2 lymph cells in peripheral blood by FCM; investigated the expression of HSP70 in tumor tissue after HIFU using SP immunohistochemical technique.Results: The kill rate of splenic lymphocyte of HIFU group was 56.98%, higher than control group(P＜0.01); the ratio of Th1/Th2 lymph cells in peripheral blood in HIFU group were 2.00, comparing to control group, P＜0.01; the expression of HSP70 in HIFU group was rigidity, but negative in control group.Conclusion: HIFU increased the kill power of lymph cell; reversed the changes of cytokine pattern from Thl to Th2 in tumor bearing mice immune function; HSP70 was over expressed in tumor tissue after HIFU.PartⅢThe Study of Mechanism for HIFU Induced Anti-tumor Immune ReactionObjective: Investigated the changes of Anti-tumor Immune function induced by HIFU.Methods: Purified the HSP70-peptide complex from HIFU-treated tumor tissue by DEAE ion chromatography and Conk-Sepharose affinity chromatograph, which injected as a tumor vaccine for the purpose of immune activation; observing tumor growth after the second attack by deferent tumor cell.Results: 10% mice had formed tumor in the group with HSP70-peptide complex injected and group with HIFU, and their six-week survivor rate was higher than control group; but the mice in this two groups did not have the resistance power to H22 cancer cell, all of mice formed tumor, their six-week survivor rate was 0-0.1.Conclusion: the resistance power to isogeny tumor cell was found in group with HIFU and HIFU group and group with HSPTO-peptide complex injected; the changes of specific anti-tumor immune function induced by HIFU maybe concerned with HSP70.PartⅣClinical Research of HIFU Treat Late Stage Pancreatic Cancer Objective: 1. roevaluate the therapeutic effect of high intensity focused ultrasound(HIFU)on the treatment of advanced pancreatic carcinoma; 2. approaching the change of immune function after HIFU in Pancreatic Cancer patients.Methods: 65 cases of advanced pancreatic carcinoma(stage ofⅢ～Ⅳ) treated by HIFU comparing to 17 cases of APC without HIFU, we observed the Change of patients' symptome, tumor appearance in imaging, and CA199 serum level in peripheral blood; detected the ratio of rhl/rh2 T lymph cells andγδT cells in peripheral blood by FCM.Results: The pain were relieved in 52 cases(80.0%) in HIFU group, the VAS Score was decreased after treatment, which has significant difference(P＜0.05); We also found tumor's blood supply reduce in 56 cases(86.1%) and CT scan confirmed HIFU group tumors' volume increase was less than control group, P＜0.01; the ratio of Th1/Th2 T lymph cells andγδT cells in HIFU group was high than that in control group(P＜0.01).Conclusion: HIFU can relieve pain of patients with advanced pancreatic carcinoma effectively and improve the quality of their lives; HIFU can increse the anti-tumour immune function.Total conclusionsHIFU treatment for malignant tumors can destroy local tumor tissue, as well as enhance host anti tumor immunity. Clinical application of HIFU to cancer favors the growing trends of surgery to noninvastive treatment, as well as is consistent with the rule of combined therapy of modern cancer treatment. HIFU is a feasible adjuvant therapy for cancers with great applied value and good prospect.