Prostatic Cancer: Aetiology and Endocrinology

Griffiths, K.; Eaton, Colby L.; Davies, Peter J.

doi:10.1159/000181307

Cited by 12 publications

(1 citation statement)

References 16 publications

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“…The relapse to insensitivity of a disease initially so sensitive to androgen-withdrawal therapy is attri¬ buted physiologically to the heterogeneity of growth requirements within the tumour (Schulze & Isaacs, 1986;Griffiths, Eaton & Davies, 1989). The normal prostate gland, or a prostate tumour, probably represents a spectrum of cellular androgen dependencies: cells with an absolute requirement for androgens, which die in their absence; cells surviving in the absence of androgens but growing more quickly in their presence; cells indirectly dependent upon androgens, requiring paracrine factors produced in androgen-responsive cells; cells totally independent of androgens.…”

Section: Introductionmentioning

confidence: 99%

Regulation of prostate growth

Davies

Eaton²

1991

Journal of Endocrinology

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137

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Section: Introductionmentioning

confidence: 99%

Regulation of prostate growth

Davies

Eaton²

1991

Journal of Endocrinology

Self Cite

137

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Antagonists of bombesin/gastrin-releasing peptide as adjuncts to agonists of luteinizing hormone–releasing hormone in the treatment of experimental prostate cancer

Pinski

Halmos

Szepesházi

et al. 1993

Cancer

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Background. Palliative methods for treatment of advanced prostatic carcinoma, including those based on luteinizing hormone‐releasing hormone (LH‐RH) agonists, cannot prevent the ultimate growth of hormone‐independent cells, and the duration of disease remission in patients with prostate cancer is limited. New therapeutic approaches combining androgen ablation therapy with other compounds must be explored. Various studies suggest that bombesin or gastrin‐releasing peptide (GRP) act as autocrine growth factors and may play a role in the initiation and progression of some cancers, including those of the prostate. Methods. The effects of treatment with bombesin/ gastrin‐releasing peptide (GRP) receptor antagonist [D‐Tpi6, Leu13ψ(CH2NH)Leu14]BN(6–14)(RC‐3095), an agonist of LH‐RH[D‐Lys6]‐LH‐RH and their combination were investigated in the androgen‐dependent Dunning R‐3327H rat prostate cancer model. Both analogs were administered by continuous subcutaneous infusion from osmotic minipumps for 7 weeks. Results. Tumor volumes and weights were significantly reduced by treatment with RC‐3095, compared with those of controls. In rats that received [D‐Lys6]‐LH‐RH, there was a greater decrease in tumor weight and volume than that produced by RC‐3095, and the weights of testes, ventral prostate, and seminal vesicles also were reduced. The combination of RC‐3095 and [D‐Lys6]‐LH‐RH had the greatest inhibitory effect on tumor growth. Histologic parameters demonstrated a significant increase of the ratio of apoptotic to mitotic indices in the groups treated with [D‐Lys6]‐LH‐RH or the combination. Serum LH and testosterone levels were greatly depressed by [D‐Lys6]‐LH‐RH or the combination. Specific high‐affinity binding sites for bombesin/GRP, epidermal growth factor (EGF), and insulin‐like growth Factor I (IGF‐I) were found on the tumor membranes. The concentration of receptors for EGF was significantly reduced by treatment with the bombesin/GRP antagonist RC‐3095. Conclusions. Combination therapy of LH‐RH analogs with bombesin antagonists such as RC‐3095 might be considered for improvement of hormonal therapy of prostate cancer.

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Histological changes in dunning prostate tumors and testes of rats treated with LH‐RH antagonist SB‐75

et al. 1991

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Rats bearing Dunning R-3327 hormone-dependent prostate tumors were treated with LH-RH antagonist SB-75 in the form of microcapsules for sustained delivery administered every 3 weeks and which released 24, 48, 72 micrograms/day respectively. The effects were compared with those of microcapsules of the agonist D-Trp-6-LH-RH releasing 25 micrograms/day. Both types of LH-RH analogs significantly inhibited tumor growth over a period of treatment lasting 8 weeks. The effect of SB-75 was dose-dependent. The total inhibition of spermatogenesis, as well as atrophic signs in the prostate and seminal vesicles, demonstrated a marked suppression of the pituitary-gonadal system by these analogs. The histological signs of tumor regression were analyzed. The vascular content of tumors did not change after the treatments, but an increased amount of connective tissue was found in the treated tumors, especially after administration of SB-75. Both the agonist and the antagonist caused a moderate decrease of the number of mitotic cells and a marked increase of apoptosis in the tumors. The apoptotic index, i.e. the percentage of tumorous glands showing signs of apoptosis, reached 40-50% in treated groups, compared to only 15% in controls. An apoptotic index of 60% was noted in a separate group of rats treated with 200 micrograms SB-75/animal/day for 3 days. The signs of enhanced apoptosis disappeared 1 week after the short-term treatment. The induction of apoptosis by LH-RH analogs seemed to be of greater importance in tumor growth inhibition than their antimitotic effect. These results extend our previous observations on the efficacy of LH-RH antagonists in inhibition of various cancers. This histopathologic evaluation clearly supports our contention that modern antagonists of LH-RH, free of edematogenic effects, inhibit the growth of Dunning prostate tumors. Because of the immediate inhibitory effects, the use of LH-RH antagonists might lead to an improvement in the clinical response in patients with prostate cancer.

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Prostatic Cancer: Aetiology and Endocrinology

Abstract: Prostate cancer is common in the male population, worldwide. Several therapies are currently available, but only greater understanding of the complex processes that govern the growth of the cancer will produce real progress in treatment.

Cited by 12 publications

References 16 publications

Regulation of prostate growth

Regulation of prostate growth

Antagonists of bombesin/gastrin-releasing peptide as adjuncts to agonists of luteinizing hormone–releasing hormone in the treatment of experimental prostate cancer

Histological changes in dunning prostate tumors and testes of rats treated with LH‐RH antagonist SB‐75

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