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Chemosensitivity of prostatic tumor cell lines under conditions of G2 block abrogation

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dc.contributor.advisor Truter EJ, Prof en
dc.contributor.author Serafin AM en
dc.date.accessioned 2016-09-22T05:51:33Z
dc.date.available 2016-09-22T05:51:33Z
dc.date.submitted 2000 en
dc.identifier.uri http://hdl.handle.net/20.500.11892/2778
dc.description.abstract Cancer of the prostate gland is now recognized as one of the principal medical problems in males. In the USA, cancer of the prostate is the second most commonly diagnosed cancer after skin cancer and the second most common cause of death from cancer after lung cancer. In South Africa, prostate cancer is the second most common cancer, with an estimated annual incidence of 19.1 per 100 000 men (Sitas, 1994). However, this incidence is probably under-estimated, due to incomplete records. Comparison of the incidence of prostate cancer in the different racial groups shows that it is the second most common malignancy in the White, Black (African) and Mixed (Coloured) race groups, and the fourth most common malignancy in Asian (Indian) men in South Africa. Metastatic prostate cancer is refractory to hormone therapy and remains incurable. Hence, novel therapeutic approaches are needed. These anticancer drugs can be tested in tumour cell lines, and cell culture methods also permit testing of optimum conditions. Evidence in squamous cell carcinoma and melanoma cells have shown that the toxicity of established anticancer drugs can be markedly enhanced when the drug is added under conditions of G2 block abrogation (Binder et al, 2000). In this study I shoe this approach is also highly effective in the prostate cancer cell lines, DU145, BM1604 and LNCaP. The cells were irradiated with 7Gy60Co y-irradiation and when the G2 block was maximally expressed, Cisplatin, Etoposide and Vinblastine, at a toxic dose of 10 percent (TD10), were added with 2mM pentoxifylline, and cell survical determined by colony assay. It was found that enhacement factors were greater in the TP53 mutant cell lines, DU145 and BM1604, than in the TP53 wild-type cell line. The response of the TP53 wild-type cell line, LNCaP, was weak for all three drugs, showing enhancement factors (Efs) of 1.10, 1.21, and 1.47 for Etoposide, Vinblastine and Cisplatin, respectively. When the drug was added 8 hours after maximum G2 block expression, the enhancement factors were found to be 1.50, 1.38 and 1.57 for Etoposide, Vinblastine and Cisplatin, respectively. In the TP53 mutant cell lines, DU145 and BM1604, Efs were found to be 330 and 3.60 respectively, for Cisplatin, 2.30 and 1.53 respectively, for Vinblastine, and 2.40 and 4.00 respectively, for Etopside, when the drugs were added at maximum G2 block expression. When the drugs were added 8 hours after maximum G2 block expression, Efs were found to be 4.11 and 4.50 respectivel, for Cisplatin, 4.82 and 2.60 respectively, for Vinblastine, and 1.50 and 1.00 respectively, for Etoposide. The observed sensitization of prostate cancer cells accomplished by this method offers a possibility of selecting particular radiation resistant TP53 mutant prostate tumours for more effective therapy. The fact that the enhancements are observed at very low toxic drug dose would allow for sparing of normal tissue. en
dc.language English en
dc.subject Medical sciences en
dc.subject Medical technologies, Bio-engineering en
dc.title Chemosensitivity of prostatic tumor cell lines under conditions of G2 block abrogation en
dc.type Masters degree en
dc.description.degree MTech : Biomedical Technology en


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