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Comparison Of In Vitro Antitumor Activity Of Pirarubicin And Adriamycin On Breast Cancer Cells And Clinical Observation On The Side Effects

Posted on:2009-04-04Degree:MasterType:Thesis
Country:ChinaCandidate:L J ZhengFull Text:PDF
GTID:2144360242981013Subject:Clinical Medicine
Abstract/Summary:PDF Full Text Request
Breast cancer is one of the most common malignant tumors of women.The incidence rate of breast cancer is the highest in the developed countries such as the United States, Canada and the Nordic regions.In the past 20 years,the incidence of breast cancer in China exhibited upward trend along with economic development and improvement of living standards.Especially in the economically developed areas and some big cities, the incidence rate of breast cancer has ranked the first of all female malignant tumors.Breast cancer has become one of the most common causes of death in the malignant tumors. Breast cancer is usually detected in patients from 40 to 59 years old about three-quarters of all breast cancer patients. The incidence of the disease in rural areas exhibits upward trend,which also can not be ignored. At present, surgery, radiotherapy, chemotherapy and endocrine treatment have been proved effect, especially chemotherapy plays an importment part in the treatment of breast cancer. Adriamycin is the most common broad-spectrum anthracycline anticancer drug used in clinic, which has obvious clinical efficacy for lung cancer, breast cancer and other solid tumors. But because of its side effects, particularly on the heart of cumulative toxicity,the applications of anthracycline is limited.THP is a semi-synthetic anthracycline,which has strong anti-cancer activity.Recent studies indicated its apparent efficacy for a variety of tumors. Anthracycline -based combined chemotherapy is the preferred first-line treatment usually. Pirarubicin is the isomer of adriamycin. The change in the structure brings great clinical benefits. It has been greatly reduced anthracycline-related cardiac toxicity, alopecia and hematological toxicity.The clinical study on THP began in 1982 and so far there are many in vitro experiments and clinical trials on the efficacy and safety of THP.But there are great differences in the technology of in vitro tumor chemosensitivity assay and apoptosis detection because of lacking of a unified national, systematic and effective standards. ATP based tumor chemosensitivity assay (ATP-TCA) and apoptosis detection technology AnnexinV were used in our study to compare the activity of growth inhibition and induction of apoptosis in vitro on human breast cancer cell line MCF-7 between THP and ADM. At the same time, the differences in the side effects between the group of THP based combined chemotherapy for breast cancer patients and the group of ADM based combined chemotherapy was studied.Objective: To compare the activity of growth inhibition and induction of apoptosis in vitro on human breast cancer cell line MCF-7 between THP and ADM,and to study the differences in the side effects between the group of THP based combined chemotherapy for breast cancer patients and the group of ADM based combined chemotherapy.Methods: ATP based tumor chemosensitivity assay (ATP-TCA) was used to establish the in vitro dose-effect curves. AnnexinV apoptosis assay method was used to compare the activity of induction of apoptosis in vitro on human breast cancer cell line MCF-7 between THP and ADM.Besides, 65 cases of female breast cancer patients were randomly selected, which was divided into the treatment group (35 cases) of THP-based combination chemotherapy and the control group (30 cases) of ADM-based combination chemotherapy.6 cycles were carried in both groups.Results:â‘ The ability of THP on the growth inhibition of MCF-7 was significantly higher than adriamycin.Both THP and adriamycin were dose-dependent.IC50 of THP was equivalent to Adriamycin's 1/3 to 1/6.The difference was significant (P<0.01); Both THP and adriamycin can induce apoptosis on MCF-7 in low concentration.THP-treated group showed higher apoptosis ratio than adriamycin group (P<0.01).â‘¡After we observed from clinical materials,we found that the side effects of THP-based combination chemotherapy group were less than that of ADM Group. Expecially,nausea and vomiting, ECG changes,alopecia were significantly lower than that of ADM Group. The differences of ECG changes and alopecia between the two groups were statistically significant (P<0.01).Conclusion:â‘ THP exhibits excellent activity of growth inhibition and apoptosis induction on the breast cancer cells.â‘¡The side effects of THP-based combination chemotherapy is lower than that of ADM group. THP-based combination chemotherapy as a first-line chemotherapy for breast cancer has a good clinical significance and social benefits.
Keywords/Search Tags:breast cancer, anthracycline, in vitro inhibition, apoptosis, side effect
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