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Treatment Of Carcinomatous Ascites Using Different Regimes Of 10-hydroxycamptothecine With Or Without Immune Agents

Posted on:2004-02-05Degree:MasterType:Thesis
Country:ChinaCandidate:Z L WeiFull Text:PDF
GTID:2144360092495931Subject:Oncology
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PrefaceThe domestic drug 10 - hydroxycamptothecin (HCPT) is one of inhibitors of topoisomerase I ( Topo I ) , cell cycle specific agent, with characteristics of long duration of effect and high content in the tumor cells. Both animals experiments and clinical investigations demonstrated that it can be effective on many sorts of tumors. As an agent for chemotherapy, it also inhibits the immunological function of human to some extent. One report from animal experiment shows that campto-thecins associated with Immune agent can raise the effect of treatment.At present, there are many sorts of drug therapies somewhat showed their curative effect on peritoneal metastasis in the advanced stage of carcinomas, but there are some problems left. High dosage often leads to better curative effect, but serious side effects can stop the further therapy sometimes. In the recent years it has been reported of Immunochemotherapy on advanced carcinomas, but it still is in the phase of attempt. In the Immunochemotherapy, the classes of the a-gents, the concentrations and the dosages, the number of times and the sequence of administration, as well as the interval, and so on, a lot of problems have to be left and expected to be resolved in the future. In the experiment, the effects of 10 - HCPT alone or associatedwith immune agents and the influence of different dosages on the treatment of the peritoneal metastasis were explored.Materials and MethodsMaterials:The parenteral solution of 10 - HCPT was bought from HSFY Pharmaceutical. Co. Ltd 010902. Recombination human interleukin -2 for injection was bought from Beijing Yuance Pharmaceutical. Co. Ltd 000701 A. Recombination interferona - 2a for injection was bought from Shenyang Sunshine Pharmaceutical. Co. Ltd 20010301. Kunming mouses were bought from the experimental animal center and Ehrlich' s ascites carcinoma ( EAC) cell was bought from the Immune department in the emu.Methods:1. To establish the model of Kunming mouse bearing the tumor of EAC. After revivification of the freezen cells, they were sterilely inoculated into the abdominal cavities of 18 -20 gram healthy Female Kunming mouses. When the increase of ascites was found, sterilely e-nough ascites was taken out during the day 6 to day 9. The cells were washed twice with PBS, then centrifuged, and cell count was performed. After the concentration was fixed at 2.5 × 107/ml, 0.2ml was inoculated in the abdominal cavities per mouse. After 48 hours, treatment was started. On the third day after the treatment finished, all the mice were killed, the results were recorded and analyzed.2. Measuring of the volume of ascites. We directly drew out the ascites when the volume was sufficient, but when there was a little, we injected 1ml PBS,after a while drew it out.3. Cell counting: We firstly counted the cells with microscopy; afterwards made smears and stained them with H - E staining and counted cells again, at last found the exact numeric values.Experiment design; This experiment adopted two ?factor analysis of variance, one factor is the different administration modality of HCPT, the other factor is the different immune agent, used SPSSIO. 0 software to do data analysis. P < 0. 05 was judged to be significant difference. And in each group there were 6 mice. The details about the groups we divided were as follows, high - dose, interval administration; 10 - HCPT 20mg/kg × 1, ip; low - dose, continual administration; 10 - HCPT 6. 6mg/kg/day x3, ip; IL-2: 1. 25 × 105u/kg/ day × 3, ip; IFNa - 2a: 2. 5 × 105u/kg/day × 3, ip; Control: the same volume of saline using the same procedure as the investigation group.ResultsComparison on the numbers of tumor cells and analysis of the effects among the investigation groups: We adopted two - factor analysis of variance (the data was LOG transformed) to compare the effects among the investigation groups. Our results showed that there were significant differences in the different administration modalities (p < 0.001) and in the differe...
Keywords/Search Tags:hydroxycamptothecine, immunochemotherapy, intraperitoneal injections
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