We measured immunoreactive EGF and TGF alpha in prostate tissue extracts obtained from 19 patient... more We measured immunoreactive EGF and TGF alpha in prostate tissue extracts obtained from 19 patients with benign prostatic hyperplasia (BPH) and 19 with cancer of the prostate (CaP). Whilst both BPH and CaP expressed EGF (BPH = 195.61 +/- 19.94 ng g-1 protein; CaP = 235.60 +/- 24.45 ng g-1 protein) and TGF alpha (BPH = 92.57 +/- 7.60 ng g-1 protein; CaP = 100.73 +/- 15.47 ng g-1 protein) in equal concentrations, the levels of EGF in any tissue extract were on average twice those of TGF alpha. Furthermore analysis of the individual growth factor data revealed a direct correlation between EGF and TGF alpha in both BPH (r = 0.72, P < 0.001) and CaP (r = 0.69, P < 0.001). When the tumours were classified according to their Gleason score, a slight but significant increase in growth factor concentrations was noted as the tumour became less differentiated. We also measured the concentrations of testosterone and dihydrotestosterone (DHT) in prostate extracts with a view of elucidating t...
Much of the earlier work on the mechanism of action of androgens in the human prostate was motiva... more Much of the earlier work on the mechanism of action of androgens in the human prostate was motivated by the need to find a suitable modality for the treatment of prostate cancer growth. One approach to the management of these steroid-regulated tumours has been hormone ablation, which is effected either by surgical or medical castration or by the administration of steroid antagonists. Whilst the immediate response to this type of treatment has on the whole been good, long-term prognosis remains poor. Indeed, although regression of the tumour has been reported in many patients who received endocrine therapy, unfortunately this was only for a limited period following which the tumour gradually progressed to a state of hormone unresponsiveness. Much has been written on the resistance of prostate cells to endocrine manipulation and the need to improve the benefits of androgen withdrawal by resorting to more radical forms of androgen deprivation (Labrie et a1. 1985). However, a more effec...
Much of the earlier work on the mechanism of action of androgens in the human prostate was motiva... more Much of the earlier work on the mechanism of action of androgens in the human prostate was motivated by the need to find a suitable modality for the treatment of prostate cancer growth. One approach to the management of these steroid-regulated tumours has been hormone ablation, which is effected either by surgical or medical castration or by the administration of steroid antagonists. Whilst the immediate response to this type of treatment has on the whole been good, long-term prognosis remains poor. Indeed, although regression of the tumour has been reported in many patients who received endocrine therapy, unfortunately this was only for a limited period following which the tumour gradually progressed to a state of hormone unresponsiveness.
A major difference between the prostate and other accessory reproductive glands is the susceptibi... more A major difference between the prostate and other accessory reproductive glands is the susceptibility of the prostate to hyperplasia in again men. Indeed, benign hyperplasia of the prostate (BPH) affects most males over 60 years of age and causes enlargement of the inner gland. When the urethra becomes constricted, treatment is required to relieve the kidney and circulation system of the damaging effects of back pressure.
To compare the efficacy of two tests, prostate-specific antigen (PSA) and skeletal alkaline phosp... more To compare the efficacy of two tests, prostate-specific antigen (PSA) and skeletal alkaline phosphatase (SAP) as staging markers to discriminate patients with cancer of the prostate (CaP) with bony metastases (M1) from those without bony metastases (Mo). Forty-seven untreated patients with Mo (n = 26) and M1 (n = 21) CaP were entered in this study. Serum concentrations for SAP and PSA were determined using two immunoassays. None of the Mo patients but 65% of the M1 patients exhibited a SAP value above the reference range (< 19 ng/ml). A corresponding cut-offpoint of 100 ng/ml for PSA showed that 27% of Mo patients and only 65% of the M1 patients exhibited a value > 100 ng/ml. This resulted in a sensitivity and specificity of 65% and 100% for SAP and 65% and 73% for PSA. Our findings suggest that SAP could become a useful marker in the evaluation of patients with newly diagnosed CaP as it seems to provide additional information concerning the skeletal status of these patients.
A retinol-binding protein has been detected in the cytosol of human prostates with benign hyperpl... more A retinol-binding protein has been detected in the cytosol of human prostates with benign hyperplasia. The binding was of high affinity and specific for retinol (Kd = 35 nM), with other retinoids such as trans-retinoic acid, retinal, and the synthetic analogues, all-trans-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nona tetraenoic acid and p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-1-propenyl] benzoic acid, showing little or no competition. The retinol binding, which sedimented as a 2S component on sucrose density gradients, was also unaffected by the addition of excess unlabeled steroid hormones. Furthermore, pretreatment of the cytosol proteins with heat and/or trypsin totally abolished the retinol binding. Parallel experiments with trans-retinoic acid suggest that the hyperplastic prostate possesses a second retinoid-binding site which is specific for retinoic acid and distinct from the retinol-binding component. Experiments with serum from patients...
SUMMARY Zinc and cadmium concentrations were measured by atomic absorption spectroscopy in normal... more SUMMARY Zinc and cadmium concentrations were measured by atomic absorption spectroscopy in normal and pathological human prostates. Our studies confirm that the values of zinc in normal tissue [6·84 ± 1·21 (s.e.m.) μmol/g] and benign prostatic hypertrophy (BPH) (6·91 ± 1·19 μmol/g) are similar, while in neoplastic tissues zinc concentrations were significantly lower (2·61 ± 0·45 μmol/g). The Cd2+ levels in BPH (23·11 ± 3·28 nmol/g) were, on the other hand, considerably higher than those found for normal tissues (5·15 ± 0·62 nmol/g). In agreement with other published reports, Cd2+ concentrations were found to be markedly increased in carcinomatous tissue (129·79 ± 22·22 nmol/g). No correlation was however established between the values for the two metals in either type of prostatic tissue. An established specific radioimmunoassay was used for the measurement of testosterone and dihydrotestosterone (DHT) and a distinct pattern emerged upon comparing these results with those for the zi...
The in-vitro metabolism of testosterone in benign and malignant prostatic tissue was examined and... more The in-vitro metabolism of testosterone in benign and malignant prostatic tissue was examined and distinct quantitative differences between the two types of specimens were observed. The major metabolite of testosterone in the hyperplastic prostate was 5α-dihydrotestosterone and a high 3α(β)-hydroxysteroid dehydrogenase activity was also detected. In the malignant tissue, 5α-reductase activity was considerably reduced and there was little or no androstanediol formed; the 17β-dehydrogenase activity was, however, higher than in the benign tissue. The decrease in 5α-reductase was always followed by a compensatory change in the 3α(β)-hydroxysteroid dehydrogenase of the malignant prostate. The present study revealed that the ratio of the mean activities of 5α-reductase to 3α(β)-hydroxysteroid dehydrogenase in the two types of specimen always remained a constant. Although the antioestrogen, tamoxifen, induced an inhibitory effect on the activities of 5α-reductase and 17β-hydroxysteroid deh...
We measured immunoreactive EGF and TGF alpha in prostate tissue extracts obtained from 19 patient... more We measured immunoreactive EGF and TGF alpha in prostate tissue extracts obtained from 19 patients with benign prostatic hyperplasia (BPH) and 19 with cancer of the prostate (CaP). Whilst both BPH and CaP expressed EGF (BPH = 195.61 +/- 19.94 ng g-1 protein; CaP = 235.60 +/- 24.45 ng g-1 protein) and TGF alpha (BPH = 92.57 +/- 7.60 ng g-1 protein; CaP = 100.73 +/- 15.47 ng g-1 protein) in equal concentrations, the levels of EGF in any tissue extract were on average twice those of TGF alpha. Furthermore analysis of the individual growth factor data revealed a direct correlation between EGF and TGF alpha in both BPH (r = 0.72, P < 0.001) and CaP (r = 0.69, P < 0.001). When the tumours were classified according to their Gleason score, a slight but significant increase in growth factor concentrations was noted as the tumour became less differentiated. We also measured the concentrations of testosterone and dihydrotestosterone (DHT) in prostate extracts with a view of elucidating t...
Much of the earlier work on the mechanism of action of androgens in the human prostate was motiva... more Much of the earlier work on the mechanism of action of androgens in the human prostate was motivated by the need to find a suitable modality for the treatment of prostate cancer growth. One approach to the management of these steroid-regulated tumours has been hormone ablation, which is effected either by surgical or medical castration or by the administration of steroid antagonists. Whilst the immediate response to this type of treatment has on the whole been good, long-term prognosis remains poor. Indeed, although regression of the tumour has been reported in many patients who received endocrine therapy, unfortunately this was only for a limited period following which the tumour gradually progressed to a state of hormone unresponsiveness. Much has been written on the resistance of prostate cells to endocrine manipulation and the need to improve the benefits of androgen withdrawal by resorting to more radical forms of androgen deprivation (Labrie et a1. 1985). However, a more effec...
Much of the earlier work on the mechanism of action of androgens in the human prostate was motiva... more Much of the earlier work on the mechanism of action of androgens in the human prostate was motivated by the need to find a suitable modality for the treatment of prostate cancer growth. One approach to the management of these steroid-regulated tumours has been hormone ablation, which is effected either by surgical or medical castration or by the administration of steroid antagonists. Whilst the immediate response to this type of treatment has on the whole been good, long-term prognosis remains poor. Indeed, although regression of the tumour has been reported in many patients who received endocrine therapy, unfortunately this was only for a limited period following which the tumour gradually progressed to a state of hormone unresponsiveness.
A major difference between the prostate and other accessory reproductive glands is the susceptibi... more A major difference between the prostate and other accessory reproductive glands is the susceptibility of the prostate to hyperplasia in again men. Indeed, benign hyperplasia of the prostate (BPH) affects most males over 60 years of age and causes enlargement of the inner gland. When the urethra becomes constricted, treatment is required to relieve the kidney and circulation system of the damaging effects of back pressure.
To compare the efficacy of two tests, prostate-specific antigen (PSA) and skeletal alkaline phosp... more To compare the efficacy of two tests, prostate-specific antigen (PSA) and skeletal alkaline phosphatase (SAP) as staging markers to discriminate patients with cancer of the prostate (CaP) with bony metastases (M1) from those without bony metastases (Mo). Forty-seven untreated patients with Mo (n = 26) and M1 (n = 21) CaP were entered in this study. Serum concentrations for SAP and PSA were determined using two immunoassays. None of the Mo patients but 65% of the M1 patients exhibited a SAP value above the reference range (< 19 ng/ml). A corresponding cut-offpoint of 100 ng/ml for PSA showed that 27% of Mo patients and only 65% of the M1 patients exhibited a value > 100 ng/ml. This resulted in a sensitivity and specificity of 65% and 100% for SAP and 65% and 73% for PSA. Our findings suggest that SAP could become a useful marker in the evaluation of patients with newly diagnosed CaP as it seems to provide additional information concerning the skeletal status of these patients.
A retinol-binding protein has been detected in the cytosol of human prostates with benign hyperpl... more A retinol-binding protein has been detected in the cytosol of human prostates with benign hyperplasia. The binding was of high affinity and specific for retinol (Kd = 35 nM), with other retinoids such as trans-retinoic acid, retinal, and the synthetic analogues, all-trans-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nona tetraenoic acid and p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-1-propenyl] benzoic acid, showing little or no competition. The retinol binding, which sedimented as a 2S component on sucrose density gradients, was also unaffected by the addition of excess unlabeled steroid hormones. Furthermore, pretreatment of the cytosol proteins with heat and/or trypsin totally abolished the retinol binding. Parallel experiments with trans-retinoic acid suggest that the hyperplastic prostate possesses a second retinoid-binding site which is specific for retinoic acid and distinct from the retinol-binding component. Experiments with serum from patients...
SUMMARY Zinc and cadmium concentrations were measured by atomic absorption spectroscopy in normal... more SUMMARY Zinc and cadmium concentrations were measured by atomic absorption spectroscopy in normal and pathological human prostates. Our studies confirm that the values of zinc in normal tissue [6·84 ± 1·21 (s.e.m.) μmol/g] and benign prostatic hypertrophy (BPH) (6·91 ± 1·19 μmol/g) are similar, while in neoplastic tissues zinc concentrations were significantly lower (2·61 ± 0·45 μmol/g). The Cd2+ levels in BPH (23·11 ± 3·28 nmol/g) were, on the other hand, considerably higher than those found for normal tissues (5·15 ± 0·62 nmol/g). In agreement with other published reports, Cd2+ concentrations were found to be markedly increased in carcinomatous tissue (129·79 ± 22·22 nmol/g). No correlation was however established between the values for the two metals in either type of prostatic tissue. An established specific radioimmunoassay was used for the measurement of testosterone and dihydrotestosterone (DHT) and a distinct pattern emerged upon comparing these results with those for the zi...
The in-vitro metabolism of testosterone in benign and malignant prostatic tissue was examined and... more The in-vitro metabolism of testosterone in benign and malignant prostatic tissue was examined and distinct quantitative differences between the two types of specimens were observed. The major metabolite of testosterone in the hyperplastic prostate was 5α-dihydrotestosterone and a high 3α(β)-hydroxysteroid dehydrogenase activity was also detected. In the malignant tissue, 5α-reductase activity was considerably reduced and there was little or no androstanediol formed; the 17β-dehydrogenase activity was, however, higher than in the benign tissue. The decrease in 5α-reductase was always followed by a compensatory change in the 3α(β)-hydroxysteroid dehydrogenase of the malignant prostate. The present study revealed that the ratio of the mean activities of 5α-reductase to 3α(β)-hydroxysteroid dehydrogenase in the two types of specimen always remained a constant. Although the antioestrogen, tamoxifen, induced an inhibitory effect on the activities of 5α-reductase and 17β-hydroxysteroid deh...
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