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Title: Regulation of prostatic carcinoma by growth factors
Author: Kehinde, Elijah Oladunni
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 1997
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The present study was designed to test the hypothesis that non-androgenic growth factor inhibitors have a role to play in the management of patients with metastatic hormone-resistant prostate cancer.;The effects of the growth factor inhibitors, Somatostatin 201-995 (SMS 201-995), Estramustine phosphate (EMP) alone and in combinations on the cellular proliferation of established human prostate cancer cell lines LNCaP, DU145 and PC3 and on cells obtained by primary culture from patients with various stages of prostate cancer were assessed using 3H thymidine incorporation assay.;Suramin (0-270 ug/ml), SMS 201-995 (0-20 ug/ml), and EMP (0-50 ug/ml) produced dose dependent growth inhibition on both hormone dependent (LNCaP) and hormone independent (PC3) prostate cancer cells and cells obtained by primary culture of prostate cancer epithelial cells. Suramin and EMP combination produced statistically significant synergism on established prostate cancer cell lines, but not on prostate cancer cells obtained by primary culture.;In a preliminary clinical trial, patients with metastatic hormone-resistant prostate cancer were randomised into two treatment groups, Group A received EMP (280 mg twice daily) while Group B received EMP (280 mg twice daily) and low dose intravenous Suramin (1 gm weekly for 6 weeks). There were 6 patients in each treatment group. The control group, made up of 6 patients, continued on maximal androgen blockade namely castration and Flutamide (250 mg three times daily) or Cyproterone acetate (100 mg three times daily). At the end of 6 months of treatment, there was statistical significant reduction of serum levels of prostate specific antigen and better pain control for patients on EMP and Suramin compared to patients who received EMP alone (P < 0.01) or patients on EMP and Suramin compared to controls (P < 0.001) (Kruskal-Wallis test).;Suramin, a non-androgen growth factor inhibitor has been shown in this study to produce significant in vitro and in vivo inhibition of the proliferation of prostate cancer cells. Its use as a novel chemotherapeutic agent for hormone-resistant prostate cancer patients alone or in combination with EMP deserves further study.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available