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- Beshara, Soheir, et al.
(author)
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Anemia associated with advanced prostatic adenocarcinoma : Effects of recombinant human erythropoietin
- 1997
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In: The Prostate. - 0270-4137 .- 1097-0045. ; 31:3, s. 153-160
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Journal article (peer-reviewed)abstract
- BACKGROUND AND METHODS: Nine patients with hormone-refractory metastatic prostatic adenocarcinoma and anemia were treated with recombinant human erythropoietin (rHuEpo) at a median dose of 150 U/kg BW 3 times a week subcutaneously. Baseline hemoglobin (Hb) ranged from 70 to 116 g/L, and the study duration was 12 weeks (median patient participation period was 8 weeks). RESULTS: Four patients demonstrated a median Hb increase of 20 g/L and were considered responders. Three patients showed a median increase of 17 g/L but required blood transfusion once, and were therefore considered as partial responders. Baseline erythropoietic status showed a significant correlation between serum Epo and Hb. Inadequate Epo production, evaluated by the observed/predicted log Epo ratio, was found in two patients. Defective bone marrow activity, demonstrated by low transferrin receptor (TfR), and hypoferremia in spite of abundant iron stores were also shown. Hemorheological investigations showed elevated plasma viscosity. CONCLUSIONS: Our results indicate that suppression of erythropoiesis can be mainly explained by the depressed marrow activity. The altered hemorheology might contribute to the anemia. This anemia could possibly be corrected with rHuEpo.
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- Pandita, RK, et al.
(author)
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Testosterone-induced prostatic growth in the rat causes bladder overactivity unrelated to detrusor hypertrophy
- 1998
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In: The Prostate. - : John Wiley and Sons, Ltd. - 0270-4137 .- 1097-0045. ; 35:2, s. 102-108
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Journal article (peer-reviewed)abstract
- BACKGROUND: Testosterone treatment of rats produces prostatic hypertrophy and detrusor overactivity. Whether or not the detrusor overactivity can be related to an increase in the responsiveness of lower urinary tract smooth muscles is not known.METHODS: Male Sprague-Dawley rats were given daily injections of testosterone propionate for 2 weeks. Effects on cystometric parameters and on the responsiveness of isolated detrusor, urethral, and prostate smooth muscle preparations to drugs and electrical field stimulation were investigated.RESULTS: Testosterone treatment increased prostatic weight twofold (controls, 768 mg; testosterone-treated, 1,478 mg), but not bladder weight (103 mg vs. 116 mg). Micturition pressure (77%), bladder capacity (75%), residual volume (56%), and micturition volume (83%) increased significantly in treated animals, and bladder overactivity developed. No effect of intraarterial doxazosin on these changes was observed. The differences in urodynamic parameters between control and testosterone-treated rats could not be correlated with changes in bladder, urethral, or prostate excitatory innervation, as revealed by responses to electrical field stimulation, or by smooth muscle responses to different contractant drugs.CONCLUSIONS: Some of the urodynamic effects seen after testosterone treatment seem to be caused by the mechanical obstruction of the enlarged prostate. Since there were no changes in smooth muscle responsiveness, it is suggested that the bladder overactivity observed can partly be related to testosterone-induced changes of the micturition reflex at the lower urinary tract, spinal, and/or supraspinal levels.
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- Häggström, S, et al.
(author)
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Expression of vascular endothelial growth factor and its receptors in the rat ventral prostate and Dunning R3327 PAP adenocarcinoma before and after castration.
- 1998
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In: The Prostate. - 0270-4137 .- 1097-0045. ; 36:2, s. 71-9
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Journal article (peer-reviewed)abstract
- BACKGROUND: Angiogenesis is important for prostate organogenesis and prostate cancer progression. It is not yet known whether androgens promote part of their control of prostate structure and function by influencing angiogenesis. The aim of this study was to explore the possible androgenic regulation of the angiogenic factor vascular endothelial growth factor (VEGF) and its receptors flt-1 and flk-1/KDR in the rat ventral prostate (VP) and Dunning R3327 PAP adenocarcinoma.METHODS: RNA was prepared from VP and tumors of intact and castrated rats. VEGF, flt-1, and flk-1/KDR mRNA levels were determined using competitive RT-PCR.RESULTS: VEGF121, VEGF165, and VEGF189 together with flt-1 and flk-1/KDR mRNA were detected. The VEGF, but not flt-1 mRNA levels were significantly decreased in the VP after castration. The Dunning tumor expressed high levels of mRNA for VEGF and its receptors compared to the VP. The flt-1 mRNA level in the tumor increased after castration, while the VEGF mRNA levels were unchanged.CONCLUSIONS: Decreased mRNA expression of VEGF, but not flt-1, was found in the rat VP after castration. However, in the Dunning tumor, castration did not alter the expression of VEGF mRNA. Moreover, elevated levels of both mRNA for VEGF and its receptors relative to the VP were observed, indicating that the VEGF system may be important for Dunning tumor development.
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- Aumüller, G., et al.
(author)
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Localization of protein gene product 9.5 immunoreactivity in derivatives of the human Wolffian duct and in prostate cancer
- 1999
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In: Prostate. - 0270-4137. ; 38:4, s. 261-267
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Journal article (peer-reviewed)abstract
- BACKGROUND. Protein gene product 9.5 (PGP 9.5) has been considered to be a neuronal marker, but it is also present in extraneuronal tissues, e.g., the human mammary gland and rat epididymis. Its presence and distribution in the developing and adult male human genital tract have been unknown. METHODS. Immunohistochemical reactions were performed on human embryonic and postnatal specimens of the male genital tract, using commercial monoclonal and polyclonal antibodies. RESULTS. PGP 9.5 immunoreactivity was found in the Wolffian duct of human embryos (55-85 mm crown-rump length). Strong reactivity was observed in mesonephric tubular cells and at the apical rim of Wolffian duct cells. Owing to their PGP 9.5 immunoreactivity, these cells could also be identified on the surface of the embryonic verumontanum, extending from the orifices of the Wolffian duct to a small stretch of the urogenital sinus. There they contrasted sharply against non-Wolffian cells. In the adult human genital tract, PGP 9.5 immunoreactive material was present in the supranuclear portion of some epithelial cells of the epididymal efferent ductules, in isolated cells of the ejaculatory ducts, and in prostate cancer specimens. In the ejaculatory ducts, the PGP 9.5- immunoreactive cells were free of immunoreactivity for semenogelin, the major secretory product of the ejaculatory-vesicular-ampullary complex, and they also lacked chromogranin A-immunoreactivity. In prostate cancer specimens, PGP 9.5 immunoreactivity was never observed in secretory cells (immunoreactive for prostate-specific antigen), but was restricted to neuroendocrine cells, where it occurred either alone or coexpressed with chromogranin A-immunoreactivity. CONCLUSIONS. PGP 9.5-immunoreactivity is prenatally distributed in the Wolffian duct and its derivations; postnatally, it is restricted to a few cells derived from the initial and terminal segment of the Wolffian duct, and to neuroendocrine cells in prostate cancer specimens.
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- Eerola, Riitta, et al.
(author)
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Immunoreactivity of recombinant human glandular kallikrein using monoclonal antibodies raised against prostate-specific antigen
- 1997
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In: Prostate. - 0270-4137. ; 31:2, s. 84-90
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Journal article (peer-reviewed)abstract
- The gene encoding human glandular kallikrein (KLK2) was expressed in Escherichia coli, and the corresponding protein (hK2) was produced by fermentation. The hK2 was characterized by Western blotting and epitope map using monoclonal antibodies (MAbs) specific for another protease, prostate- specific antigen (PSA) with high structural identity (80%). MAbs that recognized three different epitopes were bound to hK2, representing 7 out of 23 MAbs tested. One epitope was localized to the sequence region around amino acid position 78, which is believed to be glycosylated in hK2. The affinities of MAbs recognizing hK2 were similar to those for PSA, suggesting that common epitopes seem to contain very conserved structures. The results may help in designing specific diagnostic assays for the assessment of prostate cancer.
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