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Experimental Study Of Combination Of Adenovirus-Mediated IL-12 Gene With Ionization Radiation Therapy In The Murine Lewis Lung Carcinoma

Posted on:2005-11-04Degree:DoctorType:Dissertation
Country:ChinaCandidate:C Y LiuFull Text:PDF
GTID:1104360125450118Subject:Pathology and pathophysiology
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Lung cancer is a common malignant disease. The incidence rate among male tumor patients in our country has been the first place and the incidence rate among the females is also very high, only less than mammary cancer. The traditional therapeutic methods consist of operation,chemotherapy,radiotherapy and intervention treatment, all of which are not perfect. Biological treatment to the tumor is more and more emphasized. Gene therapy to the tumor may become another kind of promising treatment method.IL-12 has the strongest immunity against tumor in so many cytokines. But, effective dose of interleukin-12 (IL-12) to the tumor often cause serious toxic effects, or even lead to death, therefore, the clinical application of IL-12 was restricted. Gene therapy with IL-12 against tumor may increase the concentration of IL-12 in local tumor to increase effect and reduce the concentration in system to abate toxic effects. However, according to our experiments and other internal and external investigations, it is also found that great toxicity of IL-12 gene therapy still existed. So, this study is to treat Lewis lung carcinoma with IL-12 gene therapy and radiotherapy combinatively, then to observe the effects and toxic effects.In this experiment, adenoviruses carrying IL-12 gene was injected into tumor to transfect the cells of Lewis lung carcinoma, and combined with local radiation therapy. Different therapy projects were designed. Not only observed whether the combination treatment is able to increase effect but also observed whether these two methods have inter-promotion actions. The following results were acquired through our experiments:I. The effect of AdcmvIL-12 gene therapy to Lewis lung carcinoma was good In this study, 7x108pfu is chosen for full-IL-12 group and 3.5x108pfu for half-IL-12 group. The growth speed of tumor treated in full-IL-12 group slowed down; survival date prolonged obviously. Obvious difference appeared compared with the control group (P<0.005); there was no metastasis histologically, in early stage, a wide range of haemorrhage and necroses can be seen and plenty of lymphocytes and some neutrophilic granulocytes infiltrated. The effect of half-IL-12 group was obviously worse than the full-IL-12 group. Only the survival date was prolonged a little (P<0.05) compared with the control group. The tumor size had no difference compared with the control group. The above results show that IL-12 had strong anti-tumor effect, but also had obvious dose dependent.II. Ionization radiation's action to Lewis lung carcinoma In this experiment, 2 exposure doses were designed for study. We did not seek the best project of irradiation therapy, but only for observing the effect to the AdcmvIL-12 gene therapy caused by the changes of radiation dose and whether they could produce inter-promotion actions each other. Therefore, low-dose fractionated radiation therapy with had better effect was not adopted in this experiment. After single time 20Gy irradiation to the local tumor, the survival date obviously prolonged compared with control group (P<0.05), which showed that irradiation therapy does have effect to Lewis lung carcinoma. But the tumor size had no difference compared with control group in all time intervals. While in aspect of survival date and tumor size, 10Gy group has no difference from control group and the curative effect is obviously poorer than 20Gy group. Metastasis was found in lung in two groups.III. Treat Lewis lung carcinoma with Ionization radiation and IL-12 gene therapy combinativelyIn full-combination group 1 (firstly irradiated 20Gy, 24 hours later injected AdcmvIL-12 7x108pfu into tumor), the tumor size was much smaller than the single 20Gy irradiation group and survival date prolonged obviously (P<0.005). Compared with single full-IL-12 group, in the view of both the size and survival date of the tumor, the numeric value was a little better, but there was no statistic difference (P>0.05). Therefore, the effect of full-combination therapy mainly was the action of fu...
Keywords/Search Tags:Lewis lung carcinoma, AdcmvIL-12, Ionization irradiation, Gene therapy.
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