bluuebunny/crossref_metadata_2025 huggingface dataset:
Creatine phosphokinase isoenzymes in human prostatic tissues: A comparison between benign hyperplasia and adenocarcinoma
Authors: Truong Thomas , Lehoux Jean‐Guy , Carmel Michel , Elhilali Mostafa , Cloutier Denys
Published: February 2007

The objective of this study was to determine the distribution of creatine phosphokinase (CPK) into its three isoenzymes, MM, MB, and BB, in human prostatic tissue, in patients with benign hyperplasia (BPH) and adenocarcinoma. Specimens were obtained from 23 patients with adenocarcinoma of the prostate and 25 patients with benign hyperplasia. We also had the opportunity to analyze the CPK content in two normal prostates, the first from a 16 1/2‐year‐old boy and the second from a 9 1/2‐year‐old child. Our results showed prostate tissue to contain almost exclusively the BB isoenzyme with traces of the MB and MM.

In conclusion, this study does not show that the measurement of CPK‐BB in the prostatic tissue could be used as an index of tissue malignancy.

Dimers in both cancer and BPH as well as the specimen of normal prostate from the 16 1/2‐year‐old boy. As for the 9 1/2‐year‐old child, we found the following distribution: 39% MM, 21% MB, and 40% BB dimer. A comparison of the CPK‐BB content in benign hyperplasia and adenocarcinoma revealed no significant difference between the two groups. Furthermore, we tried to correlate prostatic tissue CPK‐BB levels with another possible tumor marker of the prostate, prostatic acid phosphatase (PAP) measured in the cytosol. No correlation was found between these two markers. We also studied the relationship of CPK‐BB and PAP content in prostatic tissue to nuclear and cytosolic androgen receptor content in human prostatic tissue. We found some correlation between CPK‐BB and androgen cytosolic receptors as well as between PAP content and androgen cytosolic receptors in patients with benign hyperplasia. No such correlation was found in the group with adenocarcinoma.
The isolation, enrichment, and comparative electron microscopic characterization of cellular components of the aged rat ventral prostate
Authors: Cooke David B. , Littleton George K.
Published: February 2007

Prostate cells were isolated from 3‐and 23‐month‐old Sprague‐Dawley rats. After sequential digestion with 0.1% collagenase at 370C, a mixed population of cells was obtained. The cells were layered on a five‐step discontinuous Percoll gradient (g/ml: 1.024, 1.043, 1.048, 1.060, 1.089), centrifuged at 3,000 rpm x 30 minutes, which produced six distinct cellular subpopulations and a fibromuscular stroma (FMS). Electron microscopic characterization of the 3‐and 23‐month‐old cellular subpopulations identified the following components, g/ml: debris and nonviable cells (1.020–1.025) nonsecretory epithelial cells (1.038–1.039), secretory epithelial cells (1.047–1.048), basal epithelial cells (1.057–1.059), differentiating epithelial cells (1.070–1.075), erythrocytes (1.085–1.089). This study demonstrates that one of the effects of age on the rat ventral prostate is an intracellular disorganization of isolated and enriched cellular components.
Induction of thymidine kinase of fetal type by androgens in the rat prostate
Authors: Gayet G. , Derré P. , Samperez S. , Jouan P.
Published: February 2007

Androgen administration to immature male rats resulted in the neosynthesis of thymidine kinase (TK) molecules in prostates. Induction was maximum 36–48 hours after hormone administration. It was specifically due to androgens and was dose‐dependent. Separate measurements of TK isoenzyme (fetal and adult types TK) activities showed that in immature animals both activities were stimulated by androgens to different extents. In adult animals, only the isoenzyme of the fetal type was concerned. Results obtained in immature and adult castrated rats showed that the increase in activity of the fetal‐type enzyme was much more important in immature than in adult animals.
Treatment of prostatic carcinoma with D‐Trp‐6‐LH‐RH: Plasma hormone levels after daily subcutaneous injections and periodic administration of delayed‐release preparations
Authors: Roger Marc , Lahlou Najiba , Nahoul Khalil , Duchier Jean , Schally Andrew V.
Published: February 2007

The hormonal effects of a delayed‐release intramuscular (IM) preparation of D‐Trp‐6‐LH‐RH (Decapeptyl microcapsules) were investigated in men aged 65–75 years. Six men with a prostatic adenoma (group A) received subcutaneously (SC) 500 μg Decapeptyl/day for seven days. Seven men with a prostatic carcinoma (group B) were given the same SC treatment, but in addition received on days 8, 28, and 56 an IM injection of Decapeptyl microcapsules. During SC treatment, plasma Decapeptyl levels rose to 2–4 ng/ml. Plasma LH, FSH, and 17‐hydroxy‐progesterone peaked on day 2, and estradiol‐17β on day 3, whereas high testosterone levels were maintained from day 2 to day 4, and then fell abruptly on day 6. In group A, hormone levels were minimal on day 12 or 14 but returned to basal on day 23. After IM injection of microcapsules on day 8, two out of seven subjects from group B exhibited the same hormonal pattern as for group A, but testosterone secretion was completely suppressed after the second IM injection. In both subjects, plasma Decapeptyl was undetectable in most samples from day 10 to day 28, but became detectable after the second injection. In five subjects from group B, plasma Decapeptyl was detectable in all plasma samples from day 10 to day 49. Testosterone levels were in the castrate range after day 24 (0.25 ± 0.03 ng/ml). Mean LH level (± SEM) decreased progressively from day 14 (65 ± 6 ng LER 907/ml) to day 56 (36 ± 2 ng/ml). These data provide evidence for the efficacy of periodic administration of Decapeptyl microcapsules for suppressing testicular secretion.
Tamoxifen decreases human prostate CPK concentration
Authors: Geller Jack , Albert Jerry D. , Kirshner Miriam , Liu Junda
Published: February 2007

Creatine phosphokinase (CPK) was measured in whole prostate tissue of patients with benign prostatic hypertrophy (BPH) who were given Tamoxifen and/or megestrol acetate for seven days prior to transurethral resection of the prostate. Tamoxifen and Tamoxifen plus Megace®, but not Megace® alone, significantly decreased CPK concentrations in whole prostate tissue in comparison to untreated controls, suggesting that CPK is an estrogen‐dependent enzyme in the prostate. CPK concentration was also measured separately in mechanically separated prostate stroma and epithelium. The levels of CPK were 2.19 times higher in stroma than epithelium. This study suggests that CPK may be a marker for estrogen stimulation of the stroma in BPH tissue.
A systematic study of age‐dependent changes in prostatic morphology and prolactin binding of ACI rats
Authors: Witorsch Raphael J. , Vick Robert S. , Abbey Louis M. , Wilson Michael J.
Published: February 2007

Histologic specimens of ventral and dorsolateral prostate from ACI male rats of varying ages (3, 6, 12, 18, 24, and 29–32 months) were examined to identify changes associated with the development of adenocarcinoma. The same specimens were examined immunohistochemically for their distribution of prolactin binding sites. At 3 months of age ventral lobes of these ACI rats exhibited normal histology and prolactin binding patterns. At 6 and 12 months of age most ventral prostate alveoli showed epithelial cell atrophy, along with occasional acini containing normal‐looking epithelial cells. Prolactin binding activity was present in most epithelial cells at 6 months of age but disappeared from atrophied cells at 12 months of age. At 18 months of age epithelial atrophy was more advanced and devoid of prolactin binding activity while zones of epithelial cell proliferation were expanded containing populations of normal‐looking cells, and cells that were either hyperplastic or dysplastic (abnormal looking), all of which were capable of binding prolactin. Older rats, 24–32 months of age, also showed prostatic adenocarcinoma in ventral prostate and these cancerous cells bound prolactin. A continuum was frequently seen between areas of normal epithelial cells, hyperplasia, dysplasia, and adenocarcinoma of ventral prostate. Morphology and prolactin binding patterns in dorsal and lateral prostates of old ACI rats were similar to young adult rats and did not contain adenocarcinoma. In conclusion, age‐dependent atrophy of the ventral prostate gland of ACI rats occurs early in life and precedes adenocarcinoma. Precancerous dysplastic changes appear to arise from normal and hyperplastic epithelial cells that are capable of binding prolactin rather than those that undergo precocious atrophy and lose their prolactin binding activity. Although atrophic epithelial cells do not appear to be progenitors of prostatic cancer, the possible relationship between precocious senescence (atrophy) and adenocarcinoma in ventral prostates of ACI rats is discussed.
Studies of androgen and estrogen binding in normal canine prostatic tissue and in epithelial and stromal cell lines derived from the canine prostate
Authors: Eaton C. L. , Hamilton T. C. , Kenvyn K. , Pierrepoint C. G.
Published: February 2007

Androgen and estrogen binding to cytosol proteins was examined in preparations derived from canine prostatic tissue and from epithelial and fibroblastoid cell lines. Binding parameters were characterized by saturation analysis using a protamine sulfate precipitation procedure and by analysis of the mobility of steroid‐binding moieties in sucrose density gradients.

Androgen‐binding studies demonstrated the presence of a single class of high‐affinity binding component (kD = 1‐2 × 10−9 M), with specificity for 5α‐dihydrotestosterone, in cytosols derived from tissue homogenates and both cell types. In estrogen‐binding studies two discrete classes of binding component were characterized of high (kD = 5‐10 × 10−10 M) and moderate (kD = 1‐2 × 10−8 M) affinities. Both species were present in cytosol derived from all three sources. The high‐affinity component displayed specificity for estradiol‐17β, and the second component displayed some capacity for androgen binding. These findings are discussed with reference to the anomalous actions of some androgens in the canine prostate and in relation to the putative role of steroids in stromal‐epithelial interrelationships.
Embryonal hyperplasia of the prostate
Authors: Bennett Betsy D. , Gardner William A.
Published: February 2007

Unusual patterns of prostatic hyperplasia require close scrutiny by the pathologist in order to distinguish them from adenocarcinoma. One such pattern, basal cell hyperplasia, has been the subject of several recent reports. We describe a second pattern, which we refer to as embryonal hyperplasia because of its resemblance to the embryonal or fetal prostate. Although this lesion bears some resemblance to basal cell hyperplasia, it differs in histochemical characteristics. A review of previous cases of this entity, which were reported as basal cell hyperplasia, suggests that they differ in ultrastructural characteristics as well. The significance of this proliferative pattern currently rests in its resemblance to prostatic adenocarcinoma, particularly when present in many chips from a transurethral resection of the prostate. Further studies, especially relating to hormone dependency, would be useful in understanding the development of this and other more atypical prostatic proliferations.
Sexual function after radical prostatectomy
Authors: Pontes J. Edson , Huben R. , Wolf R.
Published: February 2007

Forty‐five patients undergoing radical retropubic prostatectomy by a standard technique modified by the author (JEP) were interviewed regarding their sexual function prior to and after the operation. Thirty‐five patients were sexually potent prior to the surgery. Post‐operatively, 19 patients retained erectile potency (54%), although in 15 partial erections of varying degrees were noted. In 4 of these patients, erections were not satisfactory for sexual intercourse. It is evident that a significant number of patients retained sexual function after radical prostatectomy, even when no particular attention was made to preserve the neurovascular supply.
Evaluation of prostatic cancer histology and grade distribution: Experience with the colorado central cancer registry
Authors: Brooks Brenda , Miller Gary J.
Published: February 2007

Although well‐defined grading schemes for prostatic adenocarcinoma have been developed, they are not yet universally accepted by practicing surgical pathologists. The complexity of these schemes often leads surgical pathologists to develop their own modified Broders scheme. This study compared the grade distribution as obtained by a community of surgical pathologists with that obtained using the National Prostatic Cancer Project (NPCP) and Gleason grading schemes. In 1978, 308 cases of prostate cancer were reported to the Colorado Central Cancer Registry (CCCR) from the Denver Standard Metropolitan Statistical Area. Two hundred eighteen of these cases were regraded. The grade distribution as reported by the CCCR revealed a predominance of low‐grade tumors (grade I—41 %, grade II—28%, grade III—17%, grade IV—3%). Regrading of these same cases revealed a shift to higher grades (NPCP: grade I–14%, grade II–11%, grade III–37%, grade IV–29%; Gleason: pattern scores < 6–30%, score 6–24%, score 7–12%, score 8–11%, score 9–10%, score 10–4%). Twenty‐one cases of histologic variants which were not originally diagnosed were also noted (six mucinous, 12 ductal, two endometroioid, one squamous). There were 18 cases in which no evidence of carcinoma was confirmed. These results suggest that there is a tendency to underestimate grade and potentially malignant behavior when well‐defined prostatic cancer grading schemes are not applied.
Metastatic spread of the PAIII prostatic adenocarcinoma after implantation in the tail of the rat
Authors: Neubauer Blake Lee , Bemis Kerry G. , Best Kevin L. , Goode Robin L. , Merriman Ronald L. , Smith Gerald F. , Tanzer Lee R. , Hoover Dennis M.
Published: February 2007

The spontaneous metastatic spread of a suspension of PAIII prostatic adenocarcinoma cells from the tail site of implantation was analyzed over a period of 5 weeks in male Lobund‐Wistar (LW) rats. Following subcutaneous injection of the PAIII cells, the tumor metasta‐sized through the primary lymphatic drainage. PAIII microfoci were evident in the gluteal and iliac lymph nodes prior to colonization of the lungs. Growth of the primary tumor was evidenced by significant weight differences of the tails of PAIII‐bearing and control rats 1 week after tumor implantation. Time‐dependent sequential spread of the adenocarcinoma was quantitated. Significant differences were noted between PAIII‐bearing and control animals with respect to the gluteal lymph node weights (+2 weeks), iliac lymph node weights (+3 weeks), dry lung weights, and lung colony numbers (+4 weeks) after tumor implantation. During the course of these studies, the whole blood prothrombin, activated partial thromboplastin, and recalcification times for the PAIII‐bearing animals were similar to those of the control group. These findings indicate that there were no gross changes in systemic blood coagulation accompanying the metastasis of PAIII cells from the primary tumor. The tumor in LW rats produced a consistent pattern of growth and metastasis that is suitable for quantitation. The PAIII prostatic adenocarcinoma is a sensitive and reproducible system that may be useful to evaluate potential antimetastatic and cytotoxic agents for the treatment of hormone‐insensitive prostatic cancer.
Clinical evaluation of γ‐seminoprotein in prostate cancer
Authors: Kuriyama Manabu , Takeuchi Toshimi , Shinoda Ikuo , Okano Manabu , Nishiura Tsuneo
Published: February 2007

Gamma‐seminoprotein (γ‐Sm), a potential new marker for prostate cancer, has been evaluated with a sandwich‐type enzyme immunoassay (EIA). This assay system has been confirmed to have a sensitivity and detectable range of 3.0 and 3.0–100 ng/ml, respectively, with a high reproducibility (≈ 6% coefficient of variation between assays). A total of 256 serum samples were drawn from normal Japanese subjects for detection of γ‐Sm. Serum γ‐Sm was undetectable (< 3.0 ng/ml) in 26 samples from 26 females. In 230 male cases, serum γ‐Sm levels ranged from less than 3.0 to 4.0 ng/ml. These values were not related to age. An upper normal limit of 3.6 ng/ml was calculated for 99 percentile Japanese males (n = 103) over 50 years of age. Serum γ‐Sm was detected in 192 untreated male patients with urological diseases. Gamma Sm levels (mean ± SD) in each disease were as follows: prostate cancer (n = 64) 11.0 ± 17.9 ng/ml; benign prostatic hypertrophy (n = 50), 3.02 ± 0.113; bladder cancer (n = 58), 3.13 ± 0.514; and renal adenocarcinoma (n = 30), 3.26 ± 1.01. Serum γ‐Sm levels were statistically higher (p < 0.05) in the prostate cancer group, however, there was no statistical difference in γ‐Sm levels among clinical stages or histopathologic grades. Furthermore, serum γ‐Sm values showed no correlation (r = 0.3870) with prostatic acid phosphatase (PAP), but were slightly correlated to prostate antigen (PA) levels (r = 0.6980) in patients with prostate cancer. These results suggest that γ‐Sm is a potential tumor marker of prostate cancer and that serially detected serum γ‐Sm levels could be used to monitor the disease.
The sustained release of LH · RH agonist from LH · RH agonist‐polymer composite in patients with prostatic cancer
Authors: Imai Kyoichi , Yamanaka Hidetoshi , Yuasa Hisako , Yoshida Masaro , Asano Masaharu , Kaetu Isao , Yamazaki Iwao , Suzuki Keiji
Published: February 2007

Luteinizing hormone‐releasing hormone (LH·RH) agonist can be administered daily to patients with prostatic cancer with resulting clinical efficacy. A sustained drug release formulation of an LH·RH agonist, (D‐Leu6)‐des Gly‐NH210‐LH·RH ethylamide (leuprolide)‐vinyl polymer composite, was prepared by means of radiation‐induced polymerization under a supercooled state. The sustained release of leuprolide from subcutaneously implanted leuprolide‐vinyl polymer composite (14 mm in diameter and 4 mm in thickness) was obtained over a period of several months in five patients with prostatic cancer. Serum testosterone levels began to decrease on the tenth day, fell below 1 ng/ml after three weeks of implantation, and thereafter remained at the castration level until removal of the polymer composite. Clinical improvement was associated with serum hormonal changes, and support this as a novel and superior method of administration of LH·RH agonist.
Age dependency of androgen and estrogen effects on incorporation of (3H)‐thymidine by rat prostates in organ culture
Authors: Shao T. C. , Tindall D. J. , Cunningham G. R.
Published: February 2007

Organ culture of the rat ventral prostate has been evaluated as a model for studying the biological effects of androgen agonists, androgen antagonists, and estrogens. Explants were cultured for up to 8 days, and incorporation of (3H)‐thymidine and (3H)‐uridine by the explants was measured. Dihydrotestosterone (DHT) increased the incorporation of (3H)‐thymidine/μg DNA when compared with the untreated controls at 4 days, P < .05; and at 6 days, P < .01. Enhanced uptake in explants from 6 to 8‐week old rats also was observed with 10 nM estradiol (P < .05) and 10 nM cyproterone acetate (P < .02). DHT (10 nM) caused greater enhancement of uptake in explants from 3‐week‐old rats than in explants from 6‐ or 12‐week‐old rats. In contrast, estradiol (E2) increased incorporation only in prostates from the 6‐week‐old rats. Since both DHT and E3 can enhance (3H)‐thymidine uptake even though they are associated with strikingly different effects on prostate morphology, it suggests that their effects on (3H)‐thymidine incorporation are mediated by different cells.
Characterization of monoclonal antibodies raised against the prostatic cancer cell line PC‐82
Authors: Gallee Maarten P. W. , Van Vroonhoven Cornelis C. J. , Van Korput Hetty A. G. M. Der , Van Kwast Theodorus H. Der , Ten Kate Fiebo J. W. , Trapman Jan , Romijn Johan C.
Published: February 2007

For production of monoclonal antibodies (McAbs), hybrid cells were prepared by fusion of spleen cells of BALB/c mice immunized with the human prostatic cancer cell line PC‐82 and the P3‐X63Ag8. 653 murine myeloma cell line. Supernatants of approximately 500 hybrid clones were screened for prostate specific antibodies using an ELISA on PC‐82 cells. A selection of antibodies was further tested for their specificity on a large series of different tissues. A broad cross reactivity pattern was obtained. Most cross reactivity was with pancreatic tissue, kidney, and bowel. One antibody turned out to react with prostate stromal cells. Two McAbs (ER‐Pr 1 and ER‐Pr 2) reacted solely with prostatic epithelium. Monoclonal antibody affinity chromatography combined with SDS‐PAGE showed that both antibodies were directed against a 35‐kD protein. Immunoblotting revealed that this protein is identical to prostatic antigen (PA). The epitope detected by ER‐Pr 1 and ER‐Pr 2 was largely preserved after formalin‐fixation of prostatic tissues which renders these antibodies very suitable for routine examination of tissue sections.
Prostatic effects induced in dogs by chronic or acute oral administration of 5α‐reductase inhibitors
Authors: Brooks J. R. , Berman C. , Garnes D. , Giltinan D. , Malatesta P. F. , Primka R. L. , Reynolds G. F. , Rasmusson G. H. , Gordon L. R.
Published: February 2007

A series of 4‐azasteroidal 5α‐reductase inhibitors was tested in dogs to determine the effect of 1) chronic (35–44 day) oral administration on prostate size and histology and 2) acute oral administration on prostatic concentrations of testosterone (T) and dihydrotestosterone (DHT). The extent to which the results of the two tests were correlated was also studied in order to see whether the acute test could be used to predict activity in the chronic test. Six Δ1 analogs of the potent 5α‐reductase inhibitor, 4‐MA (17 β‐N,N‐diethylcarbamoyl‐4‐aza‐4‐methyl‐5α‐androstan‐3‐one) were uniformly active at low dosage levels (⩽ 3 mg/kg) in both types of assay whereas several C1‐C2 saturated analogs exhibited little activity in the chronic test. The nature of the side chain and whether there was a methyl or a proton at 4‐N did not dramatically influence the activity of Δ1 compounds. There was a broad general agreement between the results of the two kinds of test in that if a compound acutely decreased the prostatic concentration of DHT it was likely to reduce prostate size and alter prostatic histology when given on a chronic basis.
Simplified non‐enzymatic technique for isolation of epithelium and muscle from the dog prostate gland
Authors: Miller Roman J. , Donovan Michael P. , Frederickson Richard G. , Mawhinney Michael G.
Published: February 2007

Epithelium and muscle from the normal dog prostate were isolated with a rapid, simple, non‐surgical separation (NSS) technique, involving mechanical agitation of organ cubes in a high concentration (30 μM) of EDTA for tissue dispersion, and gentle pressure filtration for recovery of epithelium and muscle. Derivation of this NSS procedure utilized the guinea pig seminal vesicle, since it can be surgically separated (SS) into pure epithelium and muscle to serve as controls for the biochemical viability of NSS prepared tissues. The NSS procedure adopted for use yielded not only pure (> 95%) epithelium and muscle from intact seminal vesicle, but also activities of 5α‐reductase and concentrations of the cytosol estrophile in each tissue, which were not significantly different from the SS counterparts. In the dog prostate gland, the concentrations of 5α‐reductase and the cytosol estrophile in the NSS epithelium were 1.58 and 0.43 of the NSS muscle, respectively.
Increased recovery of androgen receptors from human prostate through the use of mersalyl: Evidence for androgen regulation of the binding sites in carcinomatous prostate
Authors: De Larminat Marie Anne , Pasik Leonardo , Bellora Oscar , Arturi Jorge , Scorticati Carlos
Published: February 2007

With a technique adapted for needle biopsies from human prostate, androgen receptors have been quantitated in normal, hyperplastic, and carcinomatous samples. An important improvement in the yield of cytosol specific binding sites was obtained when samples were pre‐incubated with the mercurial reagent mersalyl, which dissociates endogenously bound hormone receptor complexes, before the binding assay with 3H‐methyltrienolone (3H‐R1881). Androgen receptors in normal prostate tissue were found to be highest (7.81 ± 1.12 pmoles/g tissue), and significantly different from hyperplastic prostate (2.02 ± 0.55 pmoles/g tissue, p < 0.025), but not from carcinomatous samples (4.47 ± 0.79 pmoles/g tissue). Mean values for hyperplastic and carcinoma were not statistically distinguishable (p < 0.1). The clinical response to hormone therapy in 85% of 13 patients with prostatic adenocarcinoma reflected the prostatic androgen receptor content. Orchidectomy followed by estrogen administration for several months leads to a dramatic fall (8‐fold) in total androgen receptors in carcinomatous prostate, while estrogen alone did not seem to produce a significant effect. These preliminary data suggest that androgen could directly regulate its binding sites, as demonstrated earlier for other animal target organs.
Stromal and epithelial growth of the prostate during puberty
Authors: De Klerk D. P. , Lombard C. J.
Published: February 2007

In 30 male Chacma baboons, prepubertal, pubertal, and adult animals have been identified by their testicular and prostatic weights. The volume of the stromal and epithelial components of caudal prostate were calculated from morphometric determination of the percentage volume of each component and the total caudal prostate volume.

Both stromal and epithelial volumes increased at puberty and plateaued at maturity. These increases could be fitted to logistic curves that support the conclusion that stromal pubertal growth precedes epithelial pubertal growth.

The stromal contribution to prostates of increasing size followed a model distinct to that of the epithelial contribution, thus suggesting that the factors (e.g., androgens) controlling stromal and epithelial growth are not identical.

Stromal growth may be a prerequisite for pubertal epithelial development of the prostate.
Persistent blockade of the pituitary‐gonadal axis in patients with prostatic carcinoma during chronic administration of D‐Trp‐6‐LH‐RH
Authors: Gonzalez‐Barcena David , Perez‐Sanchez Patricia , Berea‐Dominguez Hector , Graef‐Sanchez Alicia , Becerril‐Morales Margarita , Comaru‐Schally Ana Maria , Schally Andrew V.
Published: February 2007

Forty patients with stage D2 prostatic carcinoma were treated for up to 30 months with D‐Trp‐6‐LH‐RH. The analog was given s.c. once daily at a dose of 1 mg/day for the first 7 days. Subsequently, the dose was reduced to 100 μg/day. In follow‐up studies, 30 men continued this therapy for up to 24 months. Blood samples were taken before the injection of the analog and 1,2,4, and 6 hours later. Serum LH, FSH, and testosterone levels were measured by RIA every month for 2 years. The initial administration of 1 mg D‐Trp‐6‐LH‐RH caused a marked elevation of LH and FSH, which lasted more than 24 hours. However, 1 month later and throughout the therapy, the basal values of LH and FSH were below the normal range and no increase in serum gonadotropins levels was obtained after administration of the analog. Initial plasma testosterone was within normal limits, but during treatment with D‐Trp‐6‐LH‐RH it fell to castration levels, and no increases were seen during the 6 hours following the injection of the analog. These results show that chronic administration of D‐Trp‐6‐LH‐RH, at the doses used, blocks the pituitary‐gonadal axis and that the escape phenomenon from the effects of the LH‐RH agonists‐induced blockade does not occur under our conditions in contrast to observations of Kerle et al with the I.C.I. Analog 118630 (8). The accumulated results reinforce the view that long‐term therapy with agonists of LH‐RH is the preferred alternative to surgical castration or therapy with estrogens in men with metastatic prostate cancer.
Biological implications of androgen dependent changes in proton‐NMR relaxation times in rat ventral prostate
Authors: Braunschweiger Paul G. , Maring Ellen M. , Machus Katy , Reynolds Kenneth , Glode L. Michael
Published: February 2007

The present studies were conducted in rat ventral prostate to determine if proton nuclear magnetic resonance (1H‐NMR) might be a useful tool to monitor physiologic changes in an androgen‐dependent target tissue after ablation and reconstitution. Ventral prostate mass and blood flow (86RbCl distribution) decreased markedly after castration. Although prostate water content was not affected by androgen ablation, 1H‐NMR spin‐lattice (T1) and spin‐spin (T2) relaxation times determined on excised prostate tissue were reduced by 10% and 50%, respectively. Testosterone propionate (Tp) reconstitution resulted in a prompt but transient increase in total water content, marked increases in prostate blood flow, and regrowth of the gland. 1H‐NMR studies indicated that although T1 lengthening after Tp was temporally related to changes in prostate water content, T1's remained prolonged after total prostate water content returned to control levels. Increased Gd‐DTPA‐dimeg modification of prostate T1 by Gadolinium‐DTPA‐dimethyl glucamine in androgen reconstituted rats implied that prostate extracellular water volumes were markedly increased during intervals of increased T1. Recovery of prostate T2 relaxation times after Tp was delayed with respect to changes in T1, water content, and prostate blood flow, but was temporally correlated with increase in prostate dry mass. Studies to assess Gd‐DTPA‐dimeg T2 modification showed that prostate T2 changes after androgen depletion and replacement reflected spin‐spin relaxation of water protons outside the in vivo Gd‐DTPA‐dimeg distribution volume.

The results from these studies indicate that 1H‐NMR and paramagnetic probes may be useful to noninvasively monitor biologically relevant changes in cellular and extracellular water in androgen‐dependent target tissues during hormonal manipulations.
The dihydrotestosterone (DHT) hypothesis of prostate cancer and its therapeutic implications
Authors: Petrow Viadimir
Published: February 2007

Data are presented showing that human prostatic adenocarcinoma depends on dihydrotestos‐terone (DHT) and not testosterone (T) for growth. It follows that androgen ablative therapy should be directed toward elimination of DHT with retention of circulating T. This can be achieved by using a 5α‐reductase inhibitor such as 6–methyleneprogesterone (6–MP) (VII). Arguments are presented showing that 6–MP (VII) is expected 1) to function as a prophylactic agent against prostate cancer, 2) to represent an attractive therapeutic modality for palliative treatment of the hormone‐responsive disease, and 3) to be compatible with other therapeutic modalities when very low prostatic levels of DHT should be within reach.
Immunocytochemical localization of metallothionein in the rat prostate gland
Authors: Bataineh Ziad M. , Heidger Paul M. , Thompson Sue Ann , Timms Barry G.
Published: February 2007

Metallothionein (MT), which binds zinc and other metals, was localized within the rat prostatic complex at light and electron microscopic levels utilizing immunocytochemistry. Two groups of mature, male Sprague‐Dawley rats were injected with cadmium chloride subcutaneously (2 mg/kg body weight) to induce the synthesis of MT, and were sacrificed 48 h postinjection. From the first group, prostatic tissue from the three lobes was prepared for light microscopy. The indirect peroxidase antiperoxidase procedure was used for MT localization using rabbit anti‐MT as the primary antibody. The three lobes of the rat prostate demonstrated a positive reaction for MT, but among the lobes variations in the intensity and localization of the reaction product occurred. Tissues from the second group of animals were prepared for electron microscopy. Using the indirect immunogold labeling technique with anti‐MT, MT localization was confirmed in the rough endoplasmic reticulum, secretory vesicles, secretory products, and subepithelial connective tissue. These localizations suggest that MT binds zinc both intra‐ and extracellularly, where it may function in zinc storage and metabolism.
Involvement of prostate in the regulation of serum levels of FSH, LH, and prolactin in male rats
Authors: Hurkadli K. S. , Joseph R. , Kadam M. S. , Sheth A. R.
Published: February 2007

Circulatory levels of LH and FSH were measured in serum of male rats (28, 35, 42, 63, 70, 77, and 207 days of age) 7 days following sham operation, castration (C), prostatectomy (P), and castration + prostatectomy (C + P). In C + P rats that were 49, 63, 70, 77, and 207 days of age, the plasma FSH was significantly elevated as compared to the C group. Administration of aqueous prostatic extract restored the circulatory FSH level in C + P animals to that observed in C animals, whereas in C animals FSH levels were suppressed, indicating inhibinlike activity. In rats 49 and 77 days of age, circulatory LH levels were significantly suppressed in C + P animals as compared to the C group. Both castration and prostatectomy alone suppressed circulatory prolactin levels. Administration of prostatic extract to castrated animals restored the prolactin levels to that of the sham‐operated control animals. Results of the present study suggest a role of the prostate in feedback regulation of FSH and prolactin.
Kinetic evaluation of the effect of LHRH analog on prostatic cancer using transrectal ultrasonotomography
Authors: Kojima Munekado , Watanabe Hiroki , Ohe Hiroshi , Miyashita Hiroaki , Inaba Tadashi
Published: February 2007

The size of the prostate was measured in 11 patients with the prostatic cancer by means of transrectal ultrasonotomography after LHRH analog ([Ser(Bu)6] LHRH) treatment. Prostate volume changed parallel to serum testosterone (T) level and decreased by 17‐62% compared with baseline after LHRH analog treatment for 4 months. Two different patterns were observed for the change in prostatic volume. Type A expanded transiently and then decreased gradually, while type B decreased continuously from the beginning with no expansion. After treatment for 4 months, the prostatic volume of type A was significantly less than that of type B. It is suggested that prostatic cancer showing a type A regression curve may be more sensitive to T, resulting in a better prognosis than type B.
Development of androgen resistance in mouse mammary tumor cells can be prevented by the antiandrogen flutamide
Authors: Luthy Isabel , Labrie Fernand
Published: February 2007

As has been clearly demonstrated in prostate and breast cancer, progression to hormone insensitivity is a major problem responsible for the usually partial and short‐lived response to antihormonal therapy. Preincubation of androgen‐sensitive Shionogi mouse carcinoma cells for 15 days in the absence of androgens causes the development of complete resistance of cell growth to androgens. Of potentially important therapeutic significance is the finding that androgen sensitivity can be maintained not only by the androgen dihydrotestosterone (DHT) but also by incubation with the pure antiandrogen Flutamide‐OH in the absence of androgens. Since androgen resistance is one of the main problems facing the treatment of prostate cancer, the possibility of avoiding or at least delaying the development of androgen resistance with a pure antiandrogen could well provide the basis for improving the success of therapy for this disease.
Circulating levels of inhibin, prolactin, TSH, LH, and FSH in benign prostatic hypertrophy before and after tumor resection
Authors: Phadke Meena A. , Vanage Geeta R. , Sheth Anil R.
Published: February 2007

Using specific radioimmunoassays, serum prolactin, TSH, LH, FSH, and inhibin levels were estimated in normal subjects and in patients with benign prostatic hyperplasia (BPH) before and after tumor resection. In the case of BPH, there was a significant rise in inhibin levels as compared to age‐matched control groups, whereas LH and FSH levels were decreased significantly. The levels of inhibin and prolactin were significantly reduced after surgery, but no consistent changes in LH, FSH, or TSH levels were noted. The changes observed in hormonal levels in the BPH patients were not related to patient's age or size of the tumor.
Nuclear roundness factor: A quantitative approach to grading in prostatic carcinoma, reliability of needle biopsy tissue, and the effect of tumor stage on usefulness
Authors: Clark Terry D. , Askin Frederic B. , Bagnell Charles R.
Published: February 2007

Morphometric analysis and histologic grading were performed on case material from 26 patients. Relative nuclear roundness factor (RNRF) was calculated and correlated with clinical course in 14 patients undergoing prostatectomy for stage A or B prostatic carcinoma. The only patients with progression of disease were two with RNRF of 1.10. RNRF in cases without progression ranged from 0.98 to 1.07. Histologic grading by the methods of Gleason or the M.D. Anderson system failed to discriminate between the progressing and nonpro‐gressing groups. However, when RNRF was measured in tumors initially diagnosed as stage C or D, four of eight were below 1.10, within the range of the nonprogressing low‐stage cases. Thus, the usefulness of morphometry and RNRF may be limited to low‐stage disease. It was additionally found that RNRF could not be reliably measured in needle biopsy specimens.
Effect of prolactin and androgens on the prostate of bonnet monkeys, Macaca radiata: I. nucleic acids, phosphatases, and citric acid
Authors: Arunakaran J. , Aruldhas M. Michael , Govindarajulu P.
Published: February 2007

The effects of prolactin (PRL), bromocriptine (Br), testosterone propionate (TP), dihydro‐testosterone (DHT), and the combinations of these androgens with PRL/Br on the growth and secretory activities of cranial and caudal prostates were studied in castrated mature monkeys, Macaco radiata. Castration decreased the body weight, organ weights, nucleic acids (DNA and RNA), phosphatases, and citric acid of cranial and caudal prostates. PRL did not alter the body weight but increased the organ weights, nucleic acids, phosphatase activities, and citric acid. Br given alone decreased the body weight and the secretory activities of prostates but caused no significant alteration in the nucleic acids. TP/DHT replacement brought back the body weight and prostatic nucleic acids to normal. It enhanced the weights, phosphatase activities, and citric acid contents of cranial and caudal prostates. PRL + TP/DHT enhanced the body weight, organ weights, and secretory activities. Br + TP/DHT decreased the body weight and secretory products of prostate but it did not produce any alteration in the organ weight and RNA content. These results suggest that PRL plays a specific stimulatory influence on monkey prostate.
Latent and clinically manifest prostatic carcinoma
Authors: Hayashi Tadashi , Taki Yoji , Ikai Kyoko , Hiura Masaru , Kiriyama Tadao , Shizuki Kohzo
Published: February 2007

In a histological study of 17 prostates excised in toto for stages B and C primary carcinoma, we found one focus of well differentiated carcinoma in each of six prostates, which, in addition to those foci, had large tumors of invasive prostatic carcinoma. In four of the six prostates, the foci were located near but separate from the main tumor, and in the remaining two they were invaded by the main tumor. These findings strongly suggest that prostatic carcinoma is multifocal in origin and that focal well differentiated carcinomas are different in biological behavior from invasive poorly differentiated carcinomas.
Activated ki‐ras oncogene in human prostatic adenocarcinoma
Authors: Peehl Donna M. , Wehner Nancy , Stamey Thomas A.
Published: February 2007

The role of cellular oncogenes in the development of human prostate cancer has not been extensively studied. A search for activated oncogenes was undertaken by testing DNA isolated from prostatic adenocarcinoma tissues for transforming activity in a 3T3 transfection assay. A transforming sequence homologous to Ki‐ras was detected in one of the samples. DNA from the other cancers was negative in the transformation assay, suggesting that the activation of oncogenes, at least those detectable by the 3T3 transfection assay, is not a frequent event in prostate cancer. Amplification of genomic oncogene sequences in prostatic tissues was also examined, but amplification of Ki‐ras, Ha‐ras, c‐myc, N‐myc, c‐sis or c‐fos was not detectable in any of the samples.
Biological significance of measurable androgen levels in the rat ventral prostate following castration
Authors: Kyprianou Natasha , Isaacs John T.
Published: February 2007

Within 12 hr after castration, there is a dramatic drop in the serum testosterone (T) levels to approximately 1.3% of the intact value (2.5 ± 0.8 ng/ml). By 1 day following castration, the serum T levels are approximately 3.3% of the intact control level. In contrast, serum 5α‐dihydrotestosterone (DHT) levels decrease to only 50% of the intact value within 12 hr postcastration and remain at a value >50% of the intact control level even following long‐term castration for up to 20 weeks. Following castration, tissue T and DHT concentrations in rat ventral prostate (RVP) exhibited a similar sequence of changes. Within 12 hr after castration, there is a substantial decrease in T to 27% and DHT to 20% of their intact values; after a further transient decrease during the subsequent 7 days, these levels remain constant with RVP at approximately 40% for T and 20% for DHT of the intact control levels even following long‐term castration. Thus castration induces only a partial withdrawal of the tissue androgens. The low but measurable androgen levels in RVP of castrated host are of adrenal origin, since following surgical adrenalectomy these remaining androgen levels become undetectable. Thus castration plus adrenalectomy produces a complete androgen withdrawal within the RVP. To determine the biological significance of the measurable androgen levels remaining following castration, the RVP cell number and the rate of prostatic DNA synthesis were compared in RVP following castration alone (ie, partial androgen withdrawal) or castration combined with surgical adrenalectomy (ie, complete androgen withdrawal). These results demonstrated that complete elimination of the remaining androgens in the RVP of long‐term castrates, by means of surgical adrenalectomy, did not induce any further reduction in either of these prostatic growth parameters. Therefore, in the rat, DHT must be decreased to a critical threshold but does not have to be completely eliminated to decrease maximally androgen effect on the prostate.
Relationship of testosterone, sex hormone binding globulin, and calculated free testosterone to subsequent clinical progress in patients with carcinoma of the prostate treated with bilateral orchidectomy or estrogens
Authors: Levell M. J. , Siddall J. K. , Rowe E. , Glashan R. W. , Robinson M. R. G. , Pidcock N. B.
Published: February 2007

The concentration in serum of testosterone, sex hormone binding globulin (SHBG), and albumin has been measured, and from these measurements free testosterone has been calculated in 75 patients with carcinoma of the prostate treated with either bilateral orchidectomy, stilbestrol, or estramustine phosphate (Estracyt). After exclusion of 3 noncompliant patients, total testosterone did not differ significantly between treatments, but free testosterone was lower in estrogen‐treated patients (5.9 ± 0.9 (SEM) pmol/l, n = 28) compared with the orchidectomized patients (23 ± 1.4 pmol/l, n = 44) (P< 0.001); all of the estrogen‐treated patients falling in the lower third of the range of the orchidectomized patients. Free testosterone did not change systematically during several years of treatment and there was no evidence of a rise with clinical deterioration. In the 33 patients with metastatic cancer treated with orchidectomy, the third with the lowest free testosterone or total testosterone showed a better survival over 2 years than the two‐thirds with higher free or total testosterone; thereafter, the advantage was lost.
Comparative study of plasma steroid and steroid glucuronide levels in normal men and in men with benign prostatic hyperplasia
Authors: Brochu Michéle , Bélanger Alain
Published: February 2007

Plasma steroids were analyzed in 16 normal men and in 10 men with prostatic benign hyperplasia (BPH). The steroids measured by radioimmunoassay include pregnenolone, 17‐OH‐pregnenolone, dehydroepiandrosterone, androst‐5‐ene‐3β, 17β‐diol, testosterone, dihydrotestosterone, androstane‐3α 17β‐diol, androstane‐3β, 17β‐diol, estrone, and estradiol as well as their glucuronide derivatives. In addition, cortisol and the sulphoconjugated form of dehydroepiandrosterone were determined. Whereas the levels of pregnenolone, pregnenolone glucuronide and 17‐OH‐pregnenolone glucuronide are not different in the two groups, the levels of 17‐OH‐pregnenolone in the BPH group (0.87 ± 0.07 ng/ml) exceed by two‐fold (p < 0.01) those observed in normal men. Plasma dehydroepiandrosterone and androst‐5‐ene‐3β, 17β‐diol concentrations are markedly elevated in the BPH group (1.49 ± 0.23 and 0.55 ± 0.08 ng/ml vs the control groups 0.43 ± 0.11 and 0.31 ± 0.05 ng/ml, respectively). Since the plasma cortisol and pregnenolone levels are comparable in these two groups, our data suggest that the elevation of plasma 17‐OH‐pregnenolone, dehydroepiandrosterone, and androst‐5‐ene‐3β, 17β‐diol reflects an increase of adrenal 17‐hydroxylase activity in patients with BPH. A slight increase of the plasma dihydrotestosterone and androsterone glucuronide concentration is also observed in men with BPH, indicating an increase of 5α‐reduced androgen formation. We have also observed, in the BPH group, a 50% decrease (p < 0.01) of plasma glucuronidated androst‐5‐ene‐3β,17β‐diol, estrone, and estradiol levels, suggesting that the transformation of unconjugated estrogenic steroids into glucuronide derivative is inhibited in BPH patients. In summary, our data indicate that adrenal C‐19 steroids might be involved in the process of BPH. Furthermore, whereas the estrogen glucuronide formation is diminished in men with BPH, the prostatic androgen metabolism as reflected by plasma dihydrotestosterone and androsterone glucuronide concentrations seems to be increased.
Stress stimuli‐induced histopathological changes in the prostate: An experimental study in the rat
Authors: Gatenbeck Lars , Aronsson Anita , Dahlgren Sven , Johansson Bengt , Strömberg Lennart
Published: February 2007

To elucidate a suggested relationship between stress stimuli and prostatitis, a histological study on the genital organs of seven rats was performed. The specimens were histopathologically examined after a 10‐day period, during which the rats had been submitted to standardized stress stimuli, and compared with corresponding organs from a control group of seven male rats. Inflammatory histopathological changes and large numbers of inflammatory cells were seen in the prostatic glands of all rats submitted to the long‐term stress stimuli. The findings agreed with those from the prostatic glands of human males with prostatitis. No corresponding changes were observed in the control group. There was no evidence indicating a bacterial origin. The results indicate a connection between stress stimuli and prostatitis.