bluuebunny/crossref_metadata_2025 huggingface dataset:
Secretion of inhibin‐like material by rat ventral prostate epithelial cells in culture
Authors: Kharbanda Kusum , Dhingra Sushma R. , Duraiswami S.
Published: February 2007

Monolayer cultures of epithelial as well as stromal components of the rat ventral prostate were established, taking advantage of differences in the requirement of sera supplementation and also in the temporal span for attachment. These monolayers were characterized and used to identify the cellular source of prostatic inhibin. The spent medium obtained from epithelial cell monolayer alone had significant inhibin‐like activity.
AgNOR staining in benign hyperplasia and carcinoma of the prostate
Authors: Mamaeva Stella , Lundgren Rolf , Elfving Peter , Limon Janusz , Mandahl Nils , Mamaev Nikolai , Henrikson Hans , Heim Sverre , Mitelman Felix
Published: February 2007

We have modified existing techniques for silver staining of nucleolar organizer regions of intact interphase cells by hypotonic swelling and by formic acid treatment to reduce background staining. This allowed the microscopic identification and counting of individual AgNORs in the nucleoli. The method was used on nine adenomatous prostatic samples (including one of normal prostate tissue outside a localized tumor) and on seven prostatic adenocarcinomas. In general, the adenomatous samples displayed fewer AgNORs (mean 13 dots/cell) than did the carcinomas (mean 24 dots/cell). Although no cells with very high AgNOR counts were found in specimens from nonmalignant tumors, two of the adenomatous prostates did have AgNOR profiles that to a large extent overlapped with those of carcinomas. A highly differentiated carcinoma (of which only very small amounts were present in the sample) had low AgNOR counts. The three moderately differentiated carcinomas had more silver‐positive material than the nonmalignant prostates but less than the three poorly differentiated carcinomas. The latter tumors also had a substantial proportion of cells with <60 AgNOR counts, something that was never seen in carcinomas with higher differentiation. The data indicate that analysis of silver staining‐positive material in intact interphase cells may help distinguish between benign and malignant prostatic tumors and between highly malignant and low malignant carcinomas.
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

Male 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

A 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

A 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

Four 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

The 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

During 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

Lymphography 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

The 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

To 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

Suramin, 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

The 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

Androgen 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

This 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

Thirty‐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.
Detection of occult micrometastases in the bone marrow of patients with prostate carcinoma
Authors: Bretton Paul R. , Melamed Myron R. , Fair William R. , Cote Richard J.
Published: February 2007

A panel of three monoclonal antibodies that recognize membrane and cytoskeletal antigens expressed by epithelial cells (T16′ C26′ and AE‐1) was used in a sensitive immunohistochemical assay to detect tumor cells in bone marrow aspirates from 20 patients with prostate cancer. Bone marrow aspirates from 2/9 (22%) patients with localized prostate cancer (stage B, 0/5; Stage C, 2/4), and 4/11 (36%) patients with metastatic prostate cancer (Stage D1′ 0/7 patients; Stage D2′ 4/4 patients) had antigen‐positive cells in their bone marrow. The patients with localized disease had conventional examinations for metastases, including radioisotope bone scans and examination of bone marrow cytology, which were negative.

The serum prostatic specific antigen (PSA) level appeared to correlate with the presence of micrometastases. Those patients with localized disease and antigen‐positive cells in the bone marrow had an average serum PSA level of 26.6 ng/ml, while the average serum PSA level in patients without antigen‐positive cells was 12.3 ng/ml. In addition, the number of antigen‐positive cells detected appeared to correlate with the stage of disease; patients with Stage C prostate cancer had an average of 10 antigen‐positive cells per one million bone marrow elements, while patients with Stage D2 disease had an average of 25 antigen‐positive cells per one million bone marrow elements.

We have demonstrated that immunohistochemical staining of bone marrow aspirates can detect occult bone marrow metastases in patients with apparently localized prostate cancer. Further follow‐up of these and a larger number of patients will be required to determine the potential clinical significance of this finding. © 1994 Wiley‐Liss, Inc.
Elevated expression of estramustine binding protein (EMBP) in prostatic intraepithelial neoplasia (PIN) compared with malignant and benign prostatic epithelia
Authors: de la Torre Manuel , Eklöv Solveig , Häggman Michael , Björk Per , Busch Christer , Nilsson Sten
Published: February 2007

The expression of estramustine‐binding protein (EMBP) was studied immunohistochemically in whole‐mount prostate sections. Specimens were taken from the prostates of 15 patients who had undergone total prostatectomy due to localized (TOd‐T2 NO MO) prostatic cancer (PC). Almost all the examined whole‐mount sections displayed areas with prostatic intraepithelial neoplasia (PIN). PIN is regarded as the main precursor of invasive PC. High‐ and low‐grade PIN expressed EMBP. The average positively stained areas accounted for averages of 69.2% and 48.7%, respectively. High‐grade PIN contained the highest EMBP levels of all the investigated (benign and malignant) epithelia, followed by moderately differentiated PC. With regard to areas with PC, the highest levels of EMBP expression (61.3%) were observed in moderately differentiated PC; poorly differentiated PC came second. Of all the examined epithelia, EMBP levels were lowest in well‐differentiated PC (25.8%). Normal prostatic epithelia and hyperplasia were characterized by low EMBP expression, although somewhat higher than well‐differentiated PC. A moderate expression (45%) was observed in the seminal vesicles. According to these results, EMBP was expressed mainly in the diseased peripheral zone (PZ), where PIN and prostatic cancer have their highest prevalence. © 1994 Wiley‐Liss, Inc.
PR92 antigen in human prostate fluid: Elevated levels in prostate cancer
Authors: Carlin Bruce I. , Marachie Jodi , Venegas Mario F. , Schaeffer Anthony J. , Shaw Norman , Hass G. Michael , Rademaker Alfred W. , Lee Chung , Grayhack John T.
Published: February 2007

In this preliminary study, we report that an enzyme‐linked immunofluorescence assay (EFLA) was developed for the determination of PR92 antigen in prostatic fluid, utilizing anti‐PR92 monoclonal antibody. Fluid samples from 64 patients were assayed. PR92 antigen was expressed as unit per microgram (U/μg) of prostatic fluid proteins. One hundred percent of men (7 out of 7) less than 50 years of age demonstrated concentrations less than 25 U/μg; 91% of men (10 out of 11) with documented carcinoma, and only 9.5% of men (2 out of 21) with benign prostatic hyperplasia, demonstrated concentrations above 230 U/μg. The mean concentration of PR92 antigen in prostatic fluid of a group of patients suspected of having prostate cancer (high‐risk group; 227 ± 42 U/μg) was significantly greater than that of those with benign prostatic hyperplasia (87 ± 23 U/μg; P = 0.05). Further evaluation of this potential marker and of other antigens within the prostatic fluid is warranted. © 1994 Wiley‐Liss, Inc.
Partial growth suppression of human prostate cancer cells by the Krev‐1 suppressor gene
Authors: Burney Tracy L. , Rockove Shammai , Eiseman Julie L. , Jacobs Stephen C. , Kyprianou Natasha
Published: February 2007

A series of functional studies were performed to assess the potential role of the ras‐related transformation suppressor gene, Krev‐1, in suppressing prostate cancer cell growth. Three human prostate cancer cell lines, PC‐3, TSU‐Pr1, and DU‐145 were transfected with a plasmid containing the Krev‐1 cDNA and a neomycin resistance gene. Selected G418‐resistant clones were isolated and expanded into cell lines. All cloned transfectants exhibited a significant reduction in their in vitro growth rates, i.e., longer doubling times, when compared to the parental cell lines. Molecular analysis of the Krev‐1 cloned transfectants revealed that they all contained variable copy numbers of the Krev‐1 gene and expressed high levels of Krev‐1 mRNA transcript, as shown by Southern and Northern analysis, respectively. To determine whether the biological properties associated with tumorigenicity were changed in these Krev‐1 transfectants, their growth characteristics were examined on the basis of their ability to a) form colonies in soft agar, and b) produce tumors in SCID mice. The majority of the Krev‐1 transfectants from the PC‐3 and TSU‐Pr1 cell lines showed a substantially reduced ability to form colonies in soft agar and produced significantly smaller tumors when inoculated into SCID mice. In contrast, there was no significant reduction in the soft agar colony‐forming ability or in vivo tumorigenicity of the DU‐145 Krev‐1 transfectants. These results suggest that the Krev‐1 suppressor gene induces partial suppression of the malignant phenotype of human prostate cancer cells containing activated ras oncogenes. © 1994 Wiley‐Liss, Inc.
Cellular PSA in benign and malignant prostate
Authors: Culkin Daniel J. , Gelder Frank B. , Mata John A. , Venable Dennis D. , Zitman Roger I.
Published: February 2007

To determine the relationship of carcinoma of the prostate and cellular production of prostate‐specific antigen, cytosol levels of PSA were measured in benign and malignant fresh prostate tissue harvested from radical prostatectomy specimens. Wedge biopsies were taken from benign (N = 21) and malignant (N = 74) prostate tissue and were immediately fixed in liquid nitrogen, and then homogenized and differentially centrifuged, and the cytosol fractions extracted. The remaining specimen was sent for routine pathologic assessment. The Hybritech methodology was used to measure the cytosol PSA and standard protein analysis was used for cytosol protein (CP) measurement. There was a significantly greater concentration of PSA in malignant tissue (P = 0.046). Also, when benign and malignant tissue were available from a single prostate (N = 17), these differences in cytosol PSA were even greater (P = 0.002). In addition, there was no significant difference when serum PSAs from the malignant tissue were ranked according to Gleason score and placed into three different histologic grades (i.e., Gleason scores 2–4, 5–6, and 7–10).
Chemo‐endocrine therapy in patients with stage D2 prostate cancer
Authors: Kubota Yoko , Nakada Teruhiro , Imai Kyoichi , Yamanaka Hidetoshi , Sakai Hideki , Saito Yutaka , Tomaru Yukio , Kitamura Koichi , Sugano Osamu , Sasagawa Isoji
Published: February 2007

There have only been a few studies of chemo‐endocrine therapy compared with endocrine therapy alone in newly diagnosed prostate cancer patients. We assessed the effects of these two therapies by comparing long‐term survival rates.

One hundred and twenty‐nine patients were entered in this study between November 1977 and March 1992. Seventy‐seven patients were treated with endocrine therapy alone. Other 52 patients received chemo‐endocrine therapy, which included orchiectomy and/or diethylstilbestrol diphosphate (DES‐DP) plus Cisplatin, with or without other cytotoxic agents. All patients had bone metastasis at the beginning of the study.

There was a significant difference in survival between patients who received endocrine therapy and chemo‐endocrine therapy (P = 0.0078). That is, survival rate was superior for the chemoendocrine therapy patients throughout the entire follow‐up period.

These data suggest that early chemo‐endocrine therapy containing Cisplatin, with or without maintenance chemotherapy, is a potentially effective treatment for newly diagnosed metastatic prostate cancer and is worth further investigation via a randomized trial.
IGF‐Binding proteins in human prostate tumor cells: Expression and regulation by 1,25‐dihydroxyvitamin D3
Authors: Drivdahl Rolf H. , Loop Stephen M. , Andress Dennis L. , Ostenson Richard C.
Published: February 2007

The expression of the six known insulin‐like growth factor binding proteins (IGFBPs) and their corresponding messenger RNAs has been examined in three cell lines established from surgical and biopsy specimens of human prostate carcinoma. All three cell lines produced both IGFBP‐4 and IGFBP‐6 and the respective mRNAs; expression of IGFBP‐6 has not been previously demonstrated in human prostate tumor cells. No other binding proteins were detected. The levels of IGFBP mRNAs were not regulated by androgens or IGF‐1, but the level of IGFBP‐6 mRNA was sharply increased by 1,25‐dihydroxyvitamin D3 (1,25(OH)D3). The stimulation was dose‐dependent with a maximum effect at 10 nM 1,25(OH)D3 and a clearly discernible effect at 0.1 nM. The results support a role for vitamin D in the control of prostate tumor growth, mediated at least in part by interaction with IGFs and specific IGFBPs.
Inhibition of androgen synthesis by 22‐hydroximino‐23,24‐bisnor‐4‐cholen‐3‐one
Authors: Li Ji‐Song , Li Yan , Son Chong , Brodie Angela M. H.
Published: February 2007

The 22‐hydroximino‐23,24‐bisnor‐4‐cholen‐3‐one (22‐oxime) was synthesized and evaluated as an inhibitor of 17α‐hydroxylase/C17,20‐lyase in rat testicular microsomes and the 5α‐reductase of human prostatic microsomes from patients with benign prostatic hypertrophy. The 22‐oxime demonstrated moderate inhibition for the 17α‐hydroxylase (Ki 74 nM vs. Km 29 nM) with progesterone as substrate and potent inhibition (Ki 18 nM vs. Km 76 nM) for the C17,20‐lyase activity with 17α‐hydroxyprogesterone as substrate. Further investigation of this enzyme with progesterone as substrate demonstrated the inhibition occurred mainly at the 17α‐hydroxylation step of the progesterone substrate. The 22‐oxime also demonstrated potent and competitive inhibition of 5α‐reductase in human prostatic microsomes (Ki 1.4 nM vs. Km 14 nM). When adult male rats were injected subcutaneously (sc) daily with 22‐oxime (50 mg/kg/day) for 21 days, the concentrations of serum and testicular testosterone were significantly reduced by 65% and 59%, respectively, in comparison to vehicle‐treated controls. Furthermore, both testosterone and DHT concentrations in rat prostatic tissue were significantly decreased by 60% and 44% compared to control tissue. Serum LH concentrations were unchanged in the 22‐oxime‐treated group compared to the control group. This indicates that the reduction in androgen concentrations in animals treated with this compound is not due to its influence on pituitary feedback mechanisms which result in reduced LH secretion. These results suggest that 22‐oxime is effective in reducing androgen synthesis through the inhibition of 17α‐hydroxylase, C17,20‐lyase, and 5α‐reductase both in vitro and in vivo.
Serum free prostate specific antigen: Isoenzymes in benign hyperplasia and cancer of the prostate
Authors: Huber Peter R. , Schmid Hans‐Peter , Mattarelli Gianfranco , Strittmatter Bernadette , van Steenbrugge Gert Jan , Maurer Andreas
Published: February 2007

Prostate specific antigen (PSA) in serum of patients with benign prostatic hyperplasia (BPH) or prostate cancer (P‐CA) not bound to α‐1‐antichymotrypsin (ACT) was analyzed by chromatofocusing. The procedure allowed the simultaneous separation of complexed and free PSA and the fractionation of the free PSA fraction into several isoenzymes. The detection of the isoenzymes was strongly dependent on the combination of antibodies introduced in the applied commercially available immunoassays (Cobas® Core, Delfia®). Isoenzymes in sera of patients with benign prostatic hyperplasia were mainly situated in the pI range of 6.6 to 7.3. Isoenzymes in sera of prostate cancer patients or in PSA from LNCAP cells were mainly situated in the pI range 7.0 to 8.3. Neuraminidase treatment of the sera shifted the isoelectric points of all three sources towards more basic pHs. An irregular glycosylation process in the dysplastic cells of the prostate is suggested to be the cause for the shift of the isoelectric points. The difference of isoenzyme distribution along the pH axis is discussed as a diagnostic tool to differentiate between BPH and P‐CA. © 1995 Wiley‐Liss, Inc.
Raloxifene (LY156758) produces antimetastatic responses and extends survival in the paiii rat prostatic adenocarcinoma model
Authors: Neubauer Blake Lee , Best Kevin L. , Counts David F. , Goode Robin L. , Hoover Dennis M. , Jones C. David , Sarosdy Michael F. , Shaar Carl J. , Tanzer Lee R. , Merriman Ronald L.
Published: February 2007

The benzothiophene antiestrogen, raloxifene (LY156758), has selective estrogen pharmacological antagonist activity in rats. The PAIII rat prostatic adenocarcinoma model was used to evaluate the effects of this agent on the lymphatic and pulmonary metastasis and survival in tumor‐bearing male Lobund‐Wistar (LW) rats. Reloxifene was inactive against colony formation of PAIII cells in vitro. Similarly, following subcutaneous (s.c.) implantation of 106 PAIII cells in the tail, s.c. administration of raloxifene (2.0, 10.0, or 20.0 mg/kg/day) for 30 days failed to demonstrate cytoreductive activity against primary tumor growth in the tail. However, in these same animals, raloxifene administration produced significant (P < 0.05) inhibition of PAIII metastasis from the primary tumor in the tail to the gluteal and iliac lymph nodes (maximal responses = 89% and 81% from control values, respectively). PAIII metastasis to the lungs was significantly inhibited by raloxifene treatment. Numbers of pulmonary foci in PAIII‐bearing rats were significantly (P < 0.05) reduced by raloxifene administration in a dose‐related manner (maximal reduction = 97% from control values). In these animals, maximal regression of 20% for ventral prostate and 21% for seminal vesicle were also seen after raloxifene administration (P < 0.05 for both). Coadministration of E2B and raloxifene had no consistent antagonistic effect upon the antitumor responses produced by raloxifene. Raloxifene (40.0 mg/kg/day for 28 days) produced marked decreases in PAIII metastasis in the lymphatic and pulmonary components. Continued administration of the compound produced significant (P < 0.05) extension of survival of PAIII‐bearing rats. Further studies are needed to define the maximal antitumor efficacy and the mechanism of action of raloxifene in urogenital solid tumor animal models. These data support the contention that raloxifene represents a class of active antimetastatic agents with potential efficacy in the treatment of hormone‐insensitive human prostatic cancer. © 1995 Wiley‐Liss, Inc.
Influence of BH3 and alkaline cation released from the reduction agent on a tandem reduction/acylation reaction—A computational study
Authors: Petkova Nevena I. , Nikolova Rositca D. , Bojilova Anka G. , Vayssilov Georgi N.
Published: February 2007

When an alkaline boron hydride is used as reduction reagent two byproducts are released, BH3 and alkaline cation, and both of them could influence the following reaction steps if a multi‐step reaction is performed in tandem one‐pot fashion. We report a theoretical study on the stability of possible complexes of the Lewis acids, BH3 and alkaline cations, with reaction intermediate, solvent molecules and basic additives in a tandem hydride reduction/acylation reaction of 3‐diethylphosphonocoumarin. Both chelate complexes of the intermediate anion with the alkali cations (Li+, Na+, or K+) and complexes of BH3 bound to C or O center of the ambident anionic intermediate have been investigated. Since the formation of the latter complexes blocks the intermediate for further acylation, the reaction could take place only if BH3 is bound in a complex with a strong base as DMAP. The binding energy of BH3 to DMAP was found higher than to the intermediate for Li+ and Na+ as counter cations, while for K+ BH3 is bound to the intermediate stronger than to DMAP. Formation of the intermediate is facilitated in presence of Li+ cations, but the alteration of the alkali cation does not influence the selectivity of the reaction—C‐acylations is preferred in all cases. © 2007 Wiley Periodicals, Inc. Int J Quantum Chem, 2007
Fingerprint verification using ridge direction distribution and minutiae correspondence
Authors: Wakahara Toru , Kimura Yoshimasa , Suzuki Akira , Shio Akio , Sano Mutsuo
Published: February 2007

Fingerprint verification technique is raising high expectations as a means of personal identification based on physical features. This paper proposes a fingerprint verification method which can achieve minutiae matching with highly accurate compensation for rotation and position deviation, as well as high speed and stability. The process flow after binarization of the gray‐scale fingerprint image is as follows. (1) Using the fingerprint ridge direction distribution in each local region, highly accurate compensation for the rotation and the position deviation between the enrolled fingerprint and the input fingerprint is performed. (2) The optimal correspondence between enrolled and input minutiae is established by fast combinatorial search. (3) By applying threshold processing to the distances of the fingerprint ridge direction distributions and the minutiae matching rate, the acceptance/rejection of the person is decided. Fingerprint image data for 80 persons×4 fingers×10 samples were collected using a commercial electrostatic capacitance semiconductor fingerprint sensor. The false reject rate and the false acceptance rate are investigated in fingerprint verification experiments, and the effectiveness of the proposed method is demonstrated. © 2007 Wiley Periodicals, Inc. Syst Comp Jpn, 38(3): 72–82, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/scj.10522
Chi‐squared and Fisher–Irwin tests of two‐by‐two tables with small sample recommendations
Authors: Campbell Ian
Published: February 2007

Two‐by‐two tables commonly arise in comparative trials and cross‐sectional studies. In medical studies, two‐by‐two tables may have a small sample size due to the rarity of a condition, or to limited resources. Current recommendations on the appropriate statistical test mostly specify the chi‐squared test for tables where the minimum expected number is at least 5 (following Fisher and Cochran), and otherwise the Fisher–Irwin test; but there is disagreement on which versions of the chi‐squared and Fisher–Irwin tests should be used. A further uncertainty is that, according to Cochran, the number 5 was chosen arbitrarily. Computer‐intensive techniques were used in this study to compare seven two‐sided tests of two‐by‐two tables in terms of their Type I errors. The tests were K. Pearson's and Yates's chi‐squared tests and the ‘N−1’ chi‐squared test (first proposed by E. Pearson), together with four versions of the Fisher–Irwin test (including two mid‐P versions). The optimum test policy was found to be analysis by the ‘N−1’ chi‐squared test when the minimum expected number is at least 1, and otherwise, by the Fisher–Irwin test by Irwin's rule (taking the total probability of tables in either tail that are as likely as, or less likely than the one observed). This policy was found to have increased power compared to Cochran's recommendations. Copyright © 2007 John Wiley & Sons, Ltd.
Increased dopamine D2High receptors in amphetamine‐sensitized rats, measured by the agonist [3H](+)PHNO
Authors: Seeman Philip , Mccormick Patrick N. , Kapur Shitij
Published: February 2007

Repeated injections of amphetamine causes animals to become sensitized and supersensitive to DA. Previous work showed that the striata from such sensitized rats revealed a 3.5‐fold increase in the density of D2High DA receptors, as measured by the guanine‐nucleotide‐sensitive component of [3H]raclopride binding. The present study was done to confirm these earlier findings by different methods and different ligands. The striata from amphetamine‐sensitized rats showed an increase of 2.2‐fold in the density of guanine‐nucleotide‐sensitive D2 receptors labeled by saturation experiments with [3H](+)PHNO. The proportion of D2High receptors was also found to increase 2.5‐fold using the method of competition between DA and [3H]domperidone. The overall 2.2–3.5‐fold increase of DA D2High receptors may explain why amphetamine‐sensitized animals are much more sensitive to DA agonists, even though the total density of D2 receptors may apparently be unchanged or even decreased. Synapse 61:263–267, 2007. © 2007 Wiley‐Liss, Inc.