bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of castration, DES, flutamide, and the 5α‐reductase inhibitor, MK‐906, on the growth of the dunning rat prostatic carcinoma, R‐3327
Authors: Brooks J. R. , Berman C. , Nguyen H. , Prahalada S. , Primka R. L. , Rasmusson G. H. , Slater E. E. 
Published: February 2007

AbstractMale rats bearing implants of the Dunning rat prostatic carcinoma, R‐3327, were used in a 42‐day study to determine the effect of castration or orally administered flutamide (FL), DES (diethylstilbestrol) or the 5α‐reductase inhibitor, MK‐906, on the growth of this androgen‐responsive cancer. The rate of growth and final weights of the tumor and the ventral prostate (VP) were all reduced (P < 0.05) by castration. Flutamide (25 mg/kg/day) significantly decreased tumor and VP weights in intact rats and castrates given 100 μg/day (SC) of testosterone propionate (TP) or dihydrotestosterone propionate (DHTP). It also significantly retarded tumor growth rate in TP‐ or DHTP‐treated castrates and was marginally effective in intact animals. DES (100 μg/kg/day) reduced (P < 0.05) tumor and VP weights of intact rats but did not significantly affect tumor growth rate or weight in castrates given TP or DHTP. These results indicated that the effect of DES on tumor growth is caused by its inhibition of the secretion or release of the gonadotropins necessary for testicular androgen production. MK‐906 (25 mg/kg/day) affected neither the gross nor the histomorphology of the tumor in intact rats or castrates given TP or DHTP. Further, it caused no histological changes in the testes of intact rats. It did, however, significantly reduce VP weight in intact animals and TP‐treated castrates but not in those given DHTP. This illustrates that the anti‐androgenicity of MK‐906 stems from its inhibition of DHT formation. The failure of MK‐906 to influence tumor growth in the TP‐treated castrates strongly suggests that the R‐3327 tumor can respond to testosterone directly. If that is true, then its growth is unlikely to be affected by a pure 5α‐reductase inhibitor such as MK‐906.In ancillary experiments, tumors from MK‐906‐treated animals were found to have reduced levels of DHT and, when assayed in vitro, to have a reduced capacity to convert [3H]‐T to [3H]‐DHT.
Transurethral microwave hyperthermia: An alternative treatment for prostadynia?
Authors: Baert L. , Willemen P. , Ameye F. , Astrahan M. , Langholz B. , Pétrovich Z. 
Published: February 2007

AbstractA total of 15 patients with severe symptoms of prostadynia who were refractory to therapy were treated with transurethral microwave hyperthermia (TUHT) in a phase I trial. All patients had pain as the predominant symptom, 9 (60%) patients gave a history of psychological problems while frequency, urgency, dysuria, nocturia, and impotence were less common symptoms.Treatment consisted of TUHT at 915 MHz given weekly for 5 weeks with a total of 68 treatment sessions and a mean of 4.5 treatments per patient. Each treatment lasted for 60 minutes. The aim was to increase the temperature measured on the urethral surface to ≧44°C. T mean for all sessions was 45.5°C. In 91% of treatments, the temperature was ≧44°C.Treatment was well tolerated in 87% patients and acute toxicity was mild. Of the 15 patients treated, 2 (13%) did not complete the treatment course due to discomfort during TUHT.Good treatment response, manifested by complete pain relief and a decrease in dysuria, was noted in 7 (47%) patients. A higher (≧ 467°C) treatment temperature correlated well with good response, P < .01. Similarly, relief of pain correlated well with the absence of a history of psychological problems, P < .01. A decrease of obstructive micturition problems was noted in 5 of the 7 patients who had this upon presentation.This study showed evidence of therapeutic activity with the use of TUHT in patients with prostadynia refractory to therapy. The response obtained was limited to less than one‐half of the patients. Complete pain relief was obtained in 4 (27%) patients. It is of interest to note that patients who had major benefit did not show evidence of psychological problems and were able to tolerate higher treatment temperatures. The latter could suggest a temperature‐related response.
Serum and prostatic growth‐promoting factors for steroid‐independent epithelial cells of adult dog prostate
Authors: Chevalier Simone , McKercher Ginette , Chapdelaine Alcide 
Published: February 2007

AbstractA growth factor‐like effect has been observed on canine prostatic epithelial cells when cultured in the presence of their homologous serum and prostatic extracts; the mitogenic activities of both preparations were dose‐dependent and not altered by charcoal treatment. The effect of dog serum decreased when the density of the epithelial cell cultures increased and was minimal on canine prostatic fibroblasts. Trace amounts of intracellular sex steroids did not contribute to epithelial cell proliferation since the presence of sex steroid action inhibitors did not alter growth rate; in those conditions, cycloheximide completely prevented cell division. When various hormones and known mitogenic agents were tested alone or in combination with steroids, none elicited an increase in the number of epithelial cells cultured in serum‐free medium or altered the proliferative effect of dog serum observed in parallel cultures. On gel filtration, dog serum or tissue cytosol showed a major mitogenic activity at an apparent molecular mass of 150 kDa and a minor one of 1.5 kDa as evaluated by gel filtration of dog serum ultrafiltrate. Acidic extraction of prostatic tissue followed by chromatography on a hydrophobic C‐18 column and subsequent gel filtration also led to the detection of the low Mr component. Thus, humoral and/or tissular factors present in vivo and different from known mitogens may be of importance as direct modulators of the basal epithelial cell growth in the adult canine prostate.
Mitogenic effects of insulin and insulin‐like growth factors on PA‐III rat prostate adenocarcinoma cells: Characterization of the receptors involved
Authors: Polychronakos Constantin , Janthly Uma , Lehoux Jean‐Guy , Koutsilieris Michael 
Published: February 2007

AbstractFour transplantable cell lines (PA‐I, II, III, and IV) derived from four Lobund‐Wistar (L‐W) rats that manifested spontaneous prostate cancer have demonstrated metastatic capacity in visceral organs. Interestingly, PA‐III cells, when deposited over the scapula or calvarium of the Lobund‐Wistar rat, could produce lytic and blastic reactions on rat skeleton. Since growth factors and growth factor receptors have been implicated in bone remodeling, cancer biology, and metastatic growth of cancer cells, we have examined 1) the effects of insulin and insulin‐like growth factors (IGF‐I and IGF‐II) on the proliferation of PA‐III cells; and 2) the presence of specific receptors for these peptides. IGF‐I (0.5 to 100 ng/ml), IGF‐II (0.5 to 100 ng/ml), and insulin (0.5 to 10 μg/ml) stimulated tritiated thymidine uptake and increased the number of PA‐III cells in culture. Receptor studies demonstrated the presence of specific bindings sites for IGF‐I and II but not for insulin. The number and affinity of the receptor sites were: IGF‐I (nb = 675 fmol/100 g protein, Kd = 0.56 nmol) and IGF‐II (nb = 225 fmol/100 g protein, Kd = 0.71 nmol). Molecular characterization of IGF binding sites by polyacrylamide gel electrophoresis under denaturing conditions indicated only the presence for the type I IGF receptor. The presence of the IGF‐I receptor and the absence of IGF‐II and insulin receptors are discussed in relation to the capacity of PA‐III cells to produce bone lesions on the L‐W rat.
Density dependent polarized secretion of a prostatic epithelial cell line
Authors: Djakiew Daniel , Pflug Beth , Delsite Robert , Lynch John H. , Onoda Makoto 
Published: February 2007

AbstractThe polarized secretions (apical/basal) of newly synthesized total protein and proteases from prostatic epithelial sheets of PA‐III cells grown in dual compartment chambers were investigated at various cell densities and culture conditions. PA‐III cells grown in a serum free defined medium (SFDM) form morphologically polarized monolayers of epithelial cells. These cells secreted their 35S‐methionine labeled total protein in a predominantly apical direction (apical/basal ratio, 4–8 fold), with a lesser proportion of protein secreted apically at lower cell densities of the PA‐III cell monolayer. PA‐III cells grown in 5% fetal calf serum (FCS) are morphologically squamous, comparable to the anaplastic phenotype, and exhibited an inversion of polarized total protein secretion (apical/basal ratio, 0.4–0.9 fold), with an increased proportion of total protein secreted in a basal direction at lower cell densities. Since the culture of PA‐III cells in FCS may approximate the anaplastic phenotype we investigated the polarized secretion of proteases from these cells at various cell densities, and compared them with the secretory pattern of protease secretion from polarized PA‐III cells cultured in SFDM. At lower cell densities of the PA‐III cells grown in FCS the polarity of protease secretion was inverted such that metalloproteinases, tissue type plasminogen activator, and a 72 kD gelatinase were secreted in a predominantly basal direction, as well as urokinase and a gelatinase of 26 kD that were secreted more or less equally into the apical and basal compartments of the chambers. On the other hand, for cultures of PA‐III cells grown in SFDM the aforementioned proteases exhibited predominantly an apically directed polarity of secretion. These results suggest that the anaplastic phenotype characterized by a loss of polarized structure may also be characterized by a functional loss or inversion of polarized secretion. The consequences of such a loss or inversion of polarized secretion would be to increase the localized concentrations of proteases along the basal domain of cells thereby facilitating degradation of the basement membrane and interstitial tissue in vivo.
Blockade of the LH response induced by the agonist D‐Trp‐6‐LHRH in rats by a highly potent LH‐RH antagonist SB‐75
Authors: Pinski J. , Yano T. , Miller G. , Schally A. V. 
Published: February 2007

AbstractDuring treatment of prostate cancer patients with luteinizing hormone‐releasing hormone agonist, a transient LH and sex steroid release, which precedes the secretion blockade, may result in a flare‐up of the disease, whereas the antagonists induce an immediate suppression. The administration of the modern, superactive LHRH antagonist SB‐75 before or together with the agonist D‐Trp‐6‐LHRH should prevent the “flare‐up” phenomena. In order to demonstrate that the LHRH antagonist can prevent the initial stimulation of gonadotropins in response to LHRH agonists, groups of 5–7 male rats were injected s.c. with the antagonist SB‐75 in doses in 100, 500, and 1,000 μg/rat 1 hour prior to or 1, 2, and 3 days before administration of D‐Trp‐6‐LHRH agonist (50 μg/rat). Supraphysiological doses of the agonist were used in order to obtain prolonged stimulation of LH release, which was necessary to study the duration and the extent of LH release inhibition. Blood samples were taken before and 2, 6, 24, 48, and 72 hours after D‐Trp‐6‐LHRH stimulation for measurement of LH levels. The administration of SB‐75 in doses of 500 and 1,000 μg/rat 3 days prior to administration of the agonist significantly lowered LH response (P < 0.01), as compared to animals injected with D‐Trp‐6‐LHRH alone. The D‐Trp‐6‐LHRH‐stimulated LH secretion was markedly more suppressed by all 3 doses of the antagonist in rats pretreated with SB‐75 2 days prior to the stimulation with the agonist. An even greater reduction in LH response could be observed in rats injected with SB‐75 1 day prior to the agonist, the magnitude of LH response being decreased by 75% with 500 μg/rat SB‐75 and by 90% with 1 mg/rat SB‐75. The LH response was virtually abolished when the antagonist, SB‐75 was given in doses of 500 or 1,000 μg/rat 1 hour prior to the D‐Trp‐6‐LHRH injection. Under these conditions, the agonist‐induced LH and testosterone secretion was completely suppressed during the whole period of the experiment. The antagonist to agonist dose ratio of 2 to 1 produced a 90% decrease in the LH response to D‐Trp‐6‐LHRH at 2 hours and 75% at 5 hours after agonist administration. The effects of LHRH decapeptide itself (500 μg/rat) on LH secretion could be totally suppressed by an injection of 50 μg/rat of SB‐75 1 hour beforehand. Likewise, the response to leuprolide (100 μg/rat) was suppressed more than 90% by an injection of 500 μg/rat of SB‐75. These findings indicate that pretreatment with the LHRH antagonist SB‐75 1 hour before the agonists can completely prevent the elevation of LH. Since a 10‐fold lower dose of SB‐75 than of LHRH suppressed the LH response, this reflects the higher affinity of SB‐75 to pituitary LHRH receptors. Exclusive or combined use of a modern LHRH antagonist such as SB‐75 with LHRH agonist, at an appropriate schedule, may lessen the risk of tumor flare in patients.
Lymphatic drainage of the prostate gland in canines
Authors: Suzuki Takanori , Kurokawa Kohei , Yamanaka Hidetoshi , Jimbo Hiroyuki 
Published: February 2007

AbstractLymphography of the penis was performed in 3 canines, and direct intraprostatic injection of India ink was carried out in 8 canines to visualize lymphatic drainage of the prostate gland. In penile lymphography, the contrast medium drained in 2 directions: (1) lymphatic drainage into the external and common iliac lymph nodes through the superficial inguinal lymph nodes; (2) lymphatic drainage into the presacral lymph nodes along the urethra and posterior wall of the pelvis. Lymphatics of the prostate gland drained in 3 directions: (1) lymphatics from the prostate gland mainly drained along the prostatic and internal iliac vessels into the internal and common iliac lymph nodes, (2) lymphatics from the dorsal region near the urinary bladder drained along the ureter into the common iliac lymph nodes, and (3) lymphatics from the apex of the prostate gland drained along the posterior wall of the pelvis into the presacral lymph nodes. Prostate cancer developed at the apex is estimated to preferentially metastasize to the presacral lymph nodes, and drug injection into the penile lymphatics is considered to be a good route to treat metastases of lymph nodes in the pelvis.
Mutant p53 expression in prostate carcinoma
Authors: van Veldhuizen Peter J. , Sadasivan Raj , Garcia Fernando , Austenfeld Mark S. , Stephens Ronald L. 
Published: February 2007

AbstractThe expression of the mutant p53 tumor suppressor gene was evaluated in 33 human prostate carcinomas. Using an immunohistochemical method with monoclonal antibodies PAb 1801 and PAb 240, 26 (79%) tumors demonstrated positive immunostaining for mutant p53. Only areas of glandular tumor were positive, with adjacent stromal elements and areas of glandular hyperplasia being negative. The predominant staining pattern was cytoplasmic. This pattern may be related to p53 binding to certain heat shock proteins (HSP 72/73), as a monoclonal antibody to these proteins demonstrated a cytoplasmic location as well. These results demonstrate that abnormal p53 expression is a frequent event in prostate cancer. © 1993 Wiley‐Liss, Inc.
The influence of finasteride on the volume of the peripheral and periurethral zones of the prostate in men with benign prostatic hyperplasia
Authors: Tempany Clare M. C. , Partin Alan W. , Zerhouni Elias A. , Zinreich S. J. , Walsh Patrick C. 
Published: February 2007

AbstractTo determine the influence of androgen deprivation induced by the potent 5α‐reductase inhibitor finasteride on the volume of the zones of the prostate, 20 symptomatic men with established BPH were randomized to one of three groups: placebo, finasteride 1 mg, and finasteride 5 mg/day. The volume of the entire prostate gland, periurethral zone, and peripheral zone and the seminal vesicles were determined by three dimensional reconstructions of magnetic resonance contoured images of the prostate. There was no significant difference between the results achieved with 1 and 5 mg of finasteride per day; thus the results in these two groups were combined. In the placebo group there was no significant change in the volume of any structure. Following treatment for 1 year with finasteride there was a significant (P <0.02) 17% decrease in total gland size (11.5 ± 3.2 cc). Similarly, there was a significant (P <0.03) decrease in the size of the periurethral zone of the prostate (6.2 ± 3 cc). Although there was also a decrease in the size of the peripheral zone of the prostate (2.8 ± 1.2 cc) this did not reach statistical significance. There was no significant change in the volume of the seminal vesicles. These findings indicate for the first time that androgen deprivation induces a significant decrease in the size of the periurethral zone of the prostate in men with established BPH. © 1993 Wiley‐Liss, Inc.
Suramin inhibits DNA damage in human prostate cancer cells treated with topoisomerase inhibitors in vitro
Authors: Yamazaki Hiroyuki , Dilworth Andrew , Myers Charles E. , Sinha Birandra K. 
Published: February 2007

AbstractSuramin, a highly sulfonated drug, has been reported to be effective against several human malignancies in vitro and in vivo, and currently is undergoing clinical trials against prostate tumors. The biochemical and molecular mechanisms for suramin's antiproliferative activity are not clear. In order to define the biochemical basis for its antitumor activity and to enhance suramin's chemotherapeutic potential while decreasing its toxicity, we have examined interactions of suramin with topoisomerase I and 11 and several clinically active anticancer drugs against the human prostate (PC3 and LNCaP) cancer cell line. While etoposide, m‐AMSA, camptothecin, and SN‐38 (the active metabolite of CPT‐11) were active in killing prostate cells as single agents, combinations of suramin and these agents were antagonistic against these cells. We found that suramin inhibited activities of purified topoisomerase I and II in vitro as measured by relaxation and cleavage assays. Further studies indicated that suramin also inhibited the drug‐induced DNA damage in vitro and in isolated nuclei. These findings indicate that combinations of suramin with topoisomerase inhibitors, for example, VP‐16, m‐AMSA, or CPT, may not be beneficial to patients receiving suramin‐containing chemotherapy. © 1993 Wiley‐Liss, Inc.This article is a US Government work and, as such, is in the public domain in the United States of America
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Mortality trend from prostate cancer in the Netherlands (1950‐1989)
Authors: Van Der Gulden J. W. J. , Kiemeney L. A. L. M. , Verbeek A. L. M. , Straatman H. 
Published: February 2007

AbstractThe trend in prostate cancer mortality in The Netherlands was studied, using data from the National Causes of Death Registry of the Central Bureau of Statistics. During the period 1950‐1989, the age‐adjusted mortality rate showed a steady rise from 20.5 to 30.6 per 100,000 man‐years. A multiplicative model was used to examine possible period effects and birth‐cohort effects separately. This analysis demonstrated that the increase in prostate cancer mortality is largely due to a birth‐cohort effect, though calendar time of death may have had a slight effect as well. Among Dutch men, a continuous increase of mortality from prostate cancer was found in consecutive birth cohorts. This finding is in contrast with that of comparable studies in other Western countries, in which a peak mortality rate was found for the cohort born at the end of the 19th century with stabilizing or declining rates for later birth cohorts. © 1994 Wiley‐Liss, Inc.
Phase I trial of high‐dose fosfestrol in hormone‐refractory adenocarcinoma of the prostate
Authors: Droz J. P. , Kattan J. , Keuppens F. , Khoury S. , De Smedt E. , Mahler C. , Denis L. 
Published: February 2007

AbstractAndrogen deprivation displays the mean therapy of advanced stage prostatic cancer. The development of hormone‐resistant disease leads to a fatal tumor progression. High‐dose fosfestrol (diethylstilbestrol disphosphate) has been suggested to circumvent hormone resistance and to induce a direct cytotoxic effect. Twenty‐one patients with hormone‐refractory prostate cancer were enrolled in a phase I trial of continuous infusion of high, daily escalating dose of fosfestrol. Fosfestrol was given in a 3.5 hr infusion in 0.9% normal saline at a starting dose of 1.5 g/d. The dose was increased daily in the same patient according to the following schedule: 1.5, 1.8, 2.4, 3.0, 3.6, 3.9, 4.5, 5.1 and 5.7 g/d. The duration of the infusion was prolonged to 7 or 10.5 hr, if a major side effect occurred. There was neither hematological nor cardiovascular toxicity. The main dose‐limiting toxicities were nausea/vomiting in 17 patients, edema in 2 patients, and more than 5% weight gain in 3 patients. The planned maximal dose was reached in 10 patients during a 3.5 hr infusion, and in 3 additional patients, after infusion prolongation. Seven patients experienced a subjective improvement. Prostatic acid phosphatase and prostatic specific antigen decreased in 4 out of 11 and in 7 out of 12 patients, respectively. The suggested dose to phase II trial is 4 g/d in 3.5 hr infusion for a duration of up to 10 days. © 1994 Wiley‐Liss, Inc.
A serum‐free defined medium capable of supporting growth of four established human prostatic carcinoma cell lines
Authors: Hedlund Tammy E. , Miller Gary J. 
Published: February 2007

AbstractThis paper describes a serum‐free defined medium (Gc) that was initially designed to support growth of the human prostatic carcinoma cell line LNCaP. Our studies indicate that this medium formulation is capable of supporting short‐term, long‐term, and clonal growth of the LNCaP cell line. Component deletion experiments have shown that the three most critical components for LNCaP short‐term growth are insulin, triiodothyronine (T3), and fetuin. Additionally, this medium was found to support short‐term and clonal growth of three other human prostatic carcinoma cell lines, DU 145, PC‐3, and ALVA‐31. The availability of such a medium should aid in the distinction of the regulatory factors involved in growth and differentiation of malignant prostatic epithelium. © 1994 Wiley‐Liss, Inc.
Effect of naftopidil on urethral obstruction in benign prostatic hyperplasia: Assessment by urodynamic studies
Authors: Yasuda Kosaku , Yamanishi Tomonori , Tojo Masaki , Nagashima Kaoru , Akimoto Susumu , Shimazaki Jun 
Published: February 2007

AbstractThirty‐two patients with voiding dysfunction attributable to symptomatic benign prostatic hyperplasia were treated with naftopidil, an α1‐blocker, at doses of 25‐75 mg/day for 4‐6 weeks. The efficacy of the drug was assessed from the changes in urinary symptoms and urodynamic data. Total symptom scores were significantly reduced after treatment (P < 0.001).Average flow rate and maximum flow rate were significantly increased (P < 0.001 and P < 0.001, respectively), and residual urine volume, residual urine rate (ratio of residual urine volume/sum of voided volume and residual urine volume), and maximum urethral closure pressure were significantly (P < 0.05, P < 0.01, and P < 0.05, respectively) reduced, and at bladder capacity, the first desire to void was significantly (P < 0.05) increased. The pressure/flow study demonstrated no changes in intravesical pressure at maximum flow, but a significant (P < 0.05) reduction in minimum urethral resistance.A mild side effect (dizziness) was noted in one patient (3.3%), which soon disappeared after the dose was decreased. The efficacy was good or excellent in 21 of 30 patients (70.0%). The drug was evaluated to be promising in the treatment of bladder outlet obstruction due to benign prostatic hyperplasia. © 1994 Wiley‐Liss, Inc.