bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endogenous protein substrates for prostatic acid phosphatase in human prostate
Authors: Lee Hansoo , Ming Chu T. , Lee Ching‐Li 
Published: February 2007

AbstractIn order to identify the endogenous phosphoprotein substrates for human prostatic acid phosphatase (PAP), cellular proteins of human normal, benign, and malignant prostatic tissues as well as carcinoma cell lines were phosphorylated by the cellular kinases in the presence of (γ‐32P)‐ATP and then were subjected to dephosphorylation reaction by PAP. Of several endogenous phosphoproteins, PAP preferentially dephosphorylated a cytosolic protein of Mr 83 kDa. The dephosphorylation of the 83 kDa phosphoprotein (designated pp83) by PAP was uniformly observed in all cells/tissues of prostate origin, and was completely inhibited by L(+)‐tartrate, the classic inhibitor of PAP. Phosphoamino acid analysis revealed that pp83 was a tyrosine‐poor phosphoprotein and was mostly dephosphorylated by PAP at serine/threonine residues rather than tyrosine residues. Further comparison of dephosphorylation rate with that of an endogenous phosphotyrosine‐containing phosphoprotein (pp53) revealed that PAP possessed both phosphoserine/threonine protein phosphatase and phosphotyrosine protein phosphatase activity. These results demonstrate that pp83 apparently is an endogenous substrate of PAP in human prostate, and that, instead of a phosphotyrosine protein specific phosphatase, PAP is a universal protein phosphatase hydrolyzing equally well the phosphotyrosine, serine, and threonine residues.
Growth hormone receptor expression in the dunning R 3327 prostatic carcinoma of the rat
Authors: Sinowatz F. , Breipohl W. , Waters M. I. , Lincoln D. , Lobie P. E. , Amselgruber W. 
Published: February 2007

AbstractThe Dunning R3327 rat carcinoma is an important model for human prostate adenocarcinoma. In the present study this tumor was further characterized by immunohistochemical demonstration of receptors for growth hormone (GH‐R). Weak GH‐R immunoreactivity was present in the secretory epithelial cells of the tumor acini. Large epithelial cells which were localized at the periphery of the acini and large cells in the stroma, which are probably derived from the epithelium (“Large neoplastic epithelial cells”), displayed a strong staining with one of the monoclonal antibodies (Mab 263) to GH‐R. The presence of GH‐R receptors in proliferating prostatic tumor cells supports the concept that GH reacts directly on prostate target tissue to facilitate tumor cell growth.
Evidence for a non‐estrogenic cytostatic effect of estramustine on human prostatic carcinoma cells in vivo
Authors: Eklöv S. , Nilsson S. , Larson A. , Björk P. , Hartley‐Asp B. 
Published: February 2007

AbstractEstramustine is one of the main metabolites of estramustine phosphate (EstracytR), a drug used in the treatment of advanced prostatic cancer. In the present study the hormone independent human prostatic carcinoma cell line DU 145 implanted subcutaneously in nude mice (NMRI) was used to investigate the mode of action of estramustine in vivo. Metaphase arrest was found in mice treated with estramustine intraperitoneally, 200 and 400 μg daily for 2 weeks, 5 days a week. A significant dose dependent decrease in the number of anaphase figures was found. A 7 to 8 fold increase in the number of abnormal metaphases, i.e., highly contracted and unaligned chromosomes, was found. Uptake and retention of 3H‐estramustine was found in tumour tissue. No increase in the mitotic index or the number of abnormal metaphases was found in animals treated with polyestradiol phosphate (EstradurinR). This is the first time evidence has been presented demonstrating the anti‐mitotic effect of estramustine in vivo.
A local direct effect of pituitary graft on growth of the lateral prostate in rats
Authors: Schacht M. J. , Niederberger C. S. , Garnett J. E. , Sensibar J. A. , Lee C. , Grayhack J. T. 
Published: February 2007

AbstractProlactin and testosterone are synergistic in stimulating growth of the rat prostate. The lateral lobe is more sensitive to this synergism than the ventral and dorsal lobes. To investigate whether prolactin acts directly in the rat prostate or indirectly through another systemic mediator, anterior pituitary grafts (1 mm3) were implanted in the lateral prostate of castrated Sprague‐Dawley rats in whom a 0.5 cm or 1.0 cm testosterone‐filled silastic tubing was implanted subcutaneously at the same time. Rats were randomly assigned to receive either the pituitary or a muscle chip of similar size grafted beneath the fascia lateral to the lateral prostate. Twenty‐one days later, serum prolactin levels were not elevated in pituitary‐grafted animals and were not significantly different from those in muscle‐grafted rats. The mean lateral prostate weight on the grafted side in pituitary‐implanted rats with 1.0 cm testosterone tubing was 43% heavier than either that of the contralateral side or the corresponding weights in muscle‐implanted rats. In pituitary‐implanted rats with 0.5 cm testosterone tubing, the mean lateral prostate weight on the grafted side was 60% heavier than either that of the contralateral side or that of the corresponding weights in muscle‐implanted rats. The weight of the ventral and dorsal lobes of the prostate was not significantly affected by the presence of pituitary grafts in one of the lateral lobes. The local effect of prolactin on the lateral prostate was further demonstrated by an overall decline in tissue concentrations of dihydrotestosterone in the grafted side. These results provided evidence to indicate that there was a direct effect of prolactin on growth of the lateral prostate in rats.
Phase II evaluation of coumarin (1,2‐benzopyrone) in metastatic prostatic carcinoma
Authors: Mohler James L. , Gomella Leonard G. , Crawford E. David , Glode L. Michael , Zippe Craig D. , Fair William R. , Marshall M. Ernest 
Published: February 2007

AbstractThe unavailability of effective treatment of metastatic hormone refractory prostatic carcinoma warrants trials of new and promising treatments. Coumarin is an investigational new drug that has produced objective tumor regression in some patients with metastatic renal cell carcinoma and malignant melanoma. Coumarin has shown activity against prostatic carcinoma in the Dunning R‐3327 rat prostatic adenocarcinoma model. Forty‐eight patients with metastatic hormone naive (5 stage D1 and 10 stage D2) or hormone refractory (33 stage D3) prostatic carcinoma of average age 67.6 years (range 46–86) and ECOG performance status of 2 or better were given 3 grams coumarin daily by mouth and evaluated monthly for toxicity and response by rigid criteria in a multicenter trial. Toxicity was limited to asymptomatic SGOT elevations in 3 patients and nausea and vomiting in 4 patients that required cessation of therapy in 2. Eligibility and protocol violations removed 6 additional patients from response evaluation. There were no complete responses. Partial responses (3 of 40 patients, 8%) occurred in 2 patients with bidimentionally measurable disease and 1 patient with disease evaluable by bone scan and elevated prostate specific antigen and prostatic acid phosphatase. The remaining patients progressed after 1 to 12 (average 4.4) months. Coumarin is a relatively nontoxic drug that may warrant further trials in a subset of patients with prostatic carcinoma.
Osteocalcin: Is it a useful marker of bone metastasis and response to treatment in advanced prostate cancer?
Authors: Arai Yoichi , Takeuchi Hideo , Oishi Kenji , Yoshida Osamu 
Published: February 2007

AbstractSerum osteocalcin (OC) is derived largely from new cellular synthesis. It is a marker for bone formation and a noninvasive specific marker of osteoblastic activity. The clinical significance of OC in monitoring prostatic cancer bone metastases was evaluated. Pretreatment serum OC levels were determined with a radioimmunoassay kit in a total of 63 patients with prostate cancer (8 with stage B, 12 with stage C, 12 with stage D1, and 31 with metastatic bone disease). The OC levels in patients with skeletal metastasis were significantly higher than those in patients without bony lesions (P<0.01). The pattern of the initial changes in OC levels were analyzed in patients with skeletal metastasis who received endocrine treatment. The pretreatment OC value is of little use in predicting the response to treatment. The patients whose OC level initially increased and remained high tended to have a shorter interval to disease progression. On the other hand, the pattern of initial changes in OC varied according to the regimen of endocrine treatment. Our study suggests that OC seem to reflect the response to treatment and might lead to the improvement in follow‐up procedures. However, the clinical significance of OC as a marker of the response of bone metastasis should be carefully discussed with regard to the direct hormonal effect on bone metabolism.
Lack of effects of post‐initiation cholesterol on 3,2′‐dimethyl‐4‐aminobiphenyl‐induced prostate carcinogenesis
Authors: Tagawa Yoshiaki , Ozaki Keisuke , Takahashi Satoru , Ogawa Kumiko , Shirai Tomoyuki 
Published: February 2007

AbstractThe effects of cholesterol on 3,2′‐dimethyl‐4‐aminobiphenyl (DMAB)‐induced rat prostate carcinogenesis were investigated in male F344 rats. Animals were given 10 subcutaneous (s.c.) injections of 50 mg/kg body weight of DMAB at 2‐week intervals, each time 2 days after transfer from 1 week on 0.75 ppm of an ethinyl estradiol (EE)‐supplemented diet to a basal diet. From week 20, the animals received treatment with cholesterol (2 or 1%, in the diet), saponin (1 or 0.2 mg/rat/week, s.c.), or clofibrate (0.3%, in the diet) for 40 weeks. Although serum cholesterol levels were significantly increased by administration of cholesterol itself, and were decreased by clofibrate, the incidences of atypical hyperplasias and carcinomas of the ventral prostate were very similar with all treatments. Thus, under the present conditions, high or low cholesteremia did not affect rat prostate lesion development.
Anti‐desmin vs. anti‐actin for quantifying the area density of prostate smooth muscle
Authors: Shapiro Ellen , Hartanto Victor , Lepor Herbert 
Published: February 2007

AbstractAnti‐desmin and anti‐actin are commercially available antibodies that bind to smooth muscle. The present study was designed to compare the staining properties of anti‐desmin and anti‐actin in the human prostate in order to determine the optimal antibody for quantifying the smooth muscle content of the human prostate. Nineteen male subjects with symptomatic BPH underwent needle biopsy of the prostate. Double‐immunoenzymatic staining was performed with peroxidase‐anti‐peroxidase (PAP) and alkaline phosphatase‐anti‐alkaline phosphatase (APAAP) techniques. Rabbit anti‐desmin:mouse anti‐human prostatic acid phosphatase and mouse anti‐actin:rabbit anti‐human prostatic acid phosphatase were utilized. Computer assisted color image analysis was performed using the Bioquant image analysis system. The percent area density of stroma and epihtelium was independent of the antibodies used. The percent area density of smooth muscle in the anti‐actin stained tissue sections was twofold greater than the anti‐desmin stained tissue sections. A direct relationship was observed for the area density of smooth muscle (r = 0.71; P = 0.0006) and the area density of connective tissue (r = 0.82; P < 0.001) determined from anti‐desmin and anti‐actin stained tissue sections. Anti‐actin represents the optimal antibody for quantifying the area density of prostate smooth muscle. The reproducibility of the immunoenzymatic staining technique is inferred from the direct relationship observed for area density of epithelium between the different staining techniques.
Inhibition of growth of PC‐82 human prostate cancer line xenografts in nude mice by bombesin antagonist RC‐3095 or combination of agonist [D‐Trp6]‐luteinizing hormone‐releasing hormone and somatostatin analog RC‐160
Authors: Milovanovic Slobodan R. , Radulovic Sinisa , Groot Kate , Schally Andrew V. 
Published: February 2007

AbstractThe effects of treatment with a bombesin receptor antagonist [D‐Tpi6, Leu13Ψ(CH2NH) Leu14]BN(6–14)(RC‐3095) and the combination of an agonist of luteinizing hormone‐releasing hormone [D‐Trp6]‐LH‐RH and somatostatin analog D‐Phe‐Cys‐Tyr‐D‐Trp‐Lys‐Val‐Cys‐Trp‐NH2 (RC‐160) were studied in nude mice bearing xenografts of the hormone‐dependent human prostate tumor PC‐82. During the 5 weeks of treatment, tumor growth was decreased in all treated groups compared with controls. Bombesin antagonist RC‐3095 and the combination of [D‐Trp6]‐LH‐RH and RC‐160 caused a greater inhibition of tumor growth than [D‐Trp6]‐LH‐RH or RC‐160 alone as based on measurement of tumor volume and percentage change in tumor volume. The largest decrease in tumor weight was also seen in the groups treated with the bombesin antagonist and with the combination of RC‐160 and [D‐Trp6]‐LH‐RH. Serum prostatic‐specific antigen levels were greatly decreased, and insulin‐like growth factor I (IGF‐I) as well as growth hormone levels were reduced in all treated groups. Specific binding sites for [D‐Trp6]‐LH‐RH, epidermal growth factor (EGF), IGF‐I, and somatostatin (SS‐14) were found in the tumor membranes. Receptors for EGF were significantly down‐regulated by treatment with the bombesin antagonist or RC‐160. Combination of LH‐RH agonists with somatostatin analog RC‐160 might be considered for improvement of hormonal therapy for prostate cancer. The finding that bombesin antagonist RC‐3095 inhibits the growth of PC‐82 prostate cancer suggests the merit of further studies to evaluate the possible usefulness of antagonists of bombesin in the management of prostatic carcinoma.
Effect of microcapsules of luteinizing hormone‐releasing hormone antagonist SB‐75 and somatostatin analog RC‐160 on endocrine status and tumor growth in the dunning R‐3327H rat prostate cancer model
Authors: Yano Tetsu , Pinski Jacek , Szepeshazi Karoly , Milovanovic Slobodan R. , Groot Kate , Schally Andrew V. 
Published: February 2007

AbstractInhibitory effects of sustained delivery systems (microcapsules) of the modern antagonist of luteinizing hormone‐releasing hormone [Ac‐D‐Nal(2)1, D‐Phe(4Cl)2, D‐Pal(3)3, D‐Cit6, D‐Ala10]LH‐RH (SB‐75) or the potent somatostatin analog D‐Phe‐Cys‐Tyr‐D‐Trp‐Lys‐Val‐Cys‐Trp‐NH2 (RC‐160) were investigated in the Dunning R‐3327H rat prostate cancer model. In the first experiment, the treatment was started 4 months after tumor transplantation, when the tumors measured approximately 2 cm3. Tumor volumes and weights were significantly reduced by SB‐75 microcapsules releasing 48 μg/day or RC‐160 microcapsules releasing 38 μg/day given alone, as compared with the control. The combination of these two analogs showed a synergistic effect. In the second experiment, the treatment was started 7 months after tumor transplantation, when the tumors were well developed and measured about 16 cm3. In addition to a significant reduction in volume, weight, and growth rate of tumors, histological signs of tumor regression were found in the groups treated with SB‐75 microcapsules releasing 72 μg/day given alone or in combination with RC‐160 microcapsules releasing 76 μg/day, but not with RC‐160 alone. No synergistic effect of the combination therapy was found in the second experiment. Serum testosterone levels decreased to undetectable levels and LH levels were also diminished within 2 weeks by administration of SB‐75 alone or in combination with RC‐160. In both experiments, the weights of testes, ventral prostate, and seminal vesicles were greatly reduced by administration of SB‐75 alone or in combination with RC‐160. Our results suggest that the combined therapy with microcapsules of SB‐75 and RC‐160, started soon after the diagnosis of prostate cancer is made, could improve therapeutic response.
Response of rat and human prostatic cancers to the novel 5α‐reductase inhibitor, SK&F 105657
Authors: Lamb John C. , Isaacs John T. , Levy Mark A. , Johnson Randall K. 
Published: February 2007

AbstractThe response of two androgen‐responsive rat prostatic cancers (i.e., Dunning R‐3327 H and G sublines) and one androgen‐responsive human prostatic cancer (i.e., PC‐82) to the 5α‐reductase inhibitor, SK&F 105657, was tested in vivo. SK&F 105657 was administered orally twice a day at a dose of 25 or 50 mg/kg/dose. The rat R‐3327 G tumor and the human PC‐82 tumor have a low to undetectable level of tissue 5α‐reductase activity and both responded to SK&F 105657 treatment with a reproducible inhibition of tumor growth. Associated with this antitumor effect was a major decrease (i.e., >70%) in tissue dihydrotestosterone (DHT) content in both tumors.By contrast, the rat R‐3327 H prostatic cancer has a much higher level of tissue 5α‐reductase activity, and neither tumor DHT content nor growth of the tumor was inhibited by treatment with SK&F 105657. Drug treatment of rats bearing R‐3227 H tumors resulted in a similar reduction in the DHT content, wet weight, and DNA content of the ventral prostate as that produced in R‐3327 G tumor‐bearing rats which experienced an antitumor response. These results suggest that SK&F 105657 can produce antitumor effects if a substantial reduction in tissue DHT is achieved. Such reduction in tissue DHT, secondary to inhibition of the tissue 5α‐reductase enzyme, appears to be more difficult to achieve in tumors than in the normal prostate. In order to achieve such a DHT reduction in tumor tissue, prostatic cancers with low 5α‐reductase activity could be treated with SK&F 105657 on a dose regimen that lowers serum DHT to surgical castration levels, while concomitantly inhibiting the already low tumor tissue 5α‐reductase activity.
Pathological and clinical associations of Ki‐67 defined growth fractions in human prostatic carcinoma
Authors: Harper M. E. , Goddard L. , Wilson D. W. , Griffiths K. , Conn I. G. , Matanhelia S. S. , Peeling W. B. 
Published: February 2007

AbstractEstimation of the growth fraction of 153 prostatic carcinoma specimens employing Ki‐67 immunostaining was undertaken and its relationship to various clinical parameters investigated. In prostate specimens, the percentage of tumour nuclei expressing Ki‐67 antigen was measured and assigned a Ki‐67 score. It was observed that high Ki‐67 scores were associated with the poorly differentiated tumours, the correlation of this proliferation marker with histological grade was found to be significant (P<0.001). No relationship was observed between the Ki‐67 score of the primary tumour with either the patient's age or with the primary tumor stage (T category). The metastatic status of the patient at diagnosis and the Ki‐67 score of the tumour were correlated (P<0.05), higher Ki‐67 scores being associated with M1 disease. Life‐table analysis of 86 patients who subsequently received androgen withdrawal therapy, was undertaken with reference to the various Ki‐67 scores of their primary tumors. A statistically significant difference in survival times was observed in patients whose Ki‐67 values were less than 1% (P<0.0001) when compared to those patients whose tumours expressed 1% and over Ki‐67 positivity, the former having longer survival times. When patients were subdivided according to their metastatic status and similar life‐table analyses were carried out, no statistical difference was found between survival times and Ki‐67 scores in M0 staged patients. In the M1 population of patients, however, those patients whose tumours were negative for Ki‐67 expression had significantly longer survival times than those patients whose tumours exhibited positive Ki‐67 staining (P<0.01). Comparing M1 staged patients whose prostate tumor cells exhibited less than 1% Ki‐67 positive nuclei with M1 staged patients whose prostate tumour cells contained 1% and higher Ki‐67 stained nuclei, a significantly longer survival time was found in the former group of patients (P˜0.0001).
Prostate‐specific antigen: Establishment of the reference range for the clinically normal prostate gland and the effect of digital rectal examination, ejaculation, and time on serum concentrations
Authors: Glenski William J. , Oesterling Joseph E. , Klee George G. , Bergstralh Erik J. 
Published: February 2007

AbstractThis study investigated the serum prostate‐specific antigen concentration in 100 healthy men (mean age, 26.3 years; range, 20–29 years) with a clinically normal prostate gland. The effect of digital rectal examination and ejaculation on the serum concentration, and the variability of the serum concentration over 1‐week and 1‐month periods were examined.In the 100 subjects, the serum prostate‐specific antigen concentration ranged from less than 0.1–2.6 ng/ml. The mean, median, and mode were 0.68 ng/ml, 0.6 ng/ml, and 0.4 ng/ml, respectively. The 97.5th percentile value was 2.1 ng/ml. The mean and median changes in the serum concentration after digital rectal examination were −0.013 ±0.11 ng/ml and 0.0 ng/ml, respectively (P = 0.59 compared with control group). The mean change after ejaculation was 0.05 ±0.12 ng/ml, and the median change was 0.0 ng/ml (P = 0.14 compared with control group). Diurnal variation showed minimal change in 16 patients over a 1‐week period. The mean change (p.m. value ‐ a.m. value) was 0.003 ng/ml (range, −0.2–0.06 ng/ml). In addition, the serum concentration showed minimal intrapatient variability in 20 patients throughout a 1‐month period; the average coefficient of variation (standard deviation/mean) in these subjects was 16.5% (range, 6.4–45.2%).These results indicate that the range in the serum concentration of prostate‐specific antigen for healthy men with a clinically normal prostate gland is significantly lower (0.0–2.6 ng/ml) than the currently employed range (0.0–4.0 ng/ml; Tandem‐R PSA assay); in addition, digital rectal examination and ejaculation have no significant effect on the serum concentration. Finally, the time of day has little effect, and the variability in the serum concentration of prostate‐specific antigen over a 1‐week and 1‐month interval is minimal.
The distribution of PSA, cathepsin‐D, and pS2 in BPH and cancer of the prostate
Authors: Yang Yong , Chisholm Geoffrey D. , Habib Fouad K. 
Published: February 2007

AbstractIn view of the limitations associated with the present tumor markers for prostate cancer, we have examined the potential expression of two further markers, Cathepsin‐D and pS2, in human prostate and attempted to link their concentrations with the histopathology of the tissue, the PSA levels and the androgenic status of the gland. Cathepsin‐D and pS2 were measured in cytosol fractions obtained from 22 patients with benign prostatic hyperplasia (BPH) and 20 patients with prostate cancer (CaP) employing itnmunoassays specific for these markers. The concentrations of Cathepsin‐D (BPH: mean ±SEM = 18.50 ±1.88 nmol/g protein; CaP = 19.75 ±2.49 nmol/g protein) and pS2 (BPH = 1,024.7 ±348.06 ng/g protein; CaP = 1,513.88 ±268.60 ng/g protein) were not different in the two tissue types, whereas PSA in BPH tissue (1,952.27 ±249.93 μg/g protein) was significantly higher than the measurements in CaP (583.75 ±104.33 μg/g protein). However, none of the tumor marker concentrations correlated with the degree of differentiation of the tumors, and we were unable to establish any correlation with the levels of testosterone and dihydrotestosterone in the tissue. In conclusion, although Cathepsin‐D and pS2 are expressed in prostate tissue, it is doubtful whether they will have an active role in the management of prostate cancer.