Proliferation Of Prostate Epithelial Cells Research Articles

Expression of p75NTR in a human prostate epithelial tumor cell line reduces nerve growth factor-induced cell growth by activation of programmed cell death.

Epithelial expression of the 75-kDa low-affinity neurotrophin receptor (p75NTR) is inversely associated with the malignant progression of the human prostate. To elucidate the function of p75NTR in the prostate, the human prostate epithelial tumor cell line TSU-pr1, which does not express p75NTR, was stably and transiently transfected with the cDNA for the receptor. The stably transfected cells were assessed for levels of p75NTR expression and categorized into low, intermediate, and high receptor-expressing clones by immunocytochemical and immunoblot analyses. Incorporation of [3H]thymidine was used to assess nerve growth factor (NGF)-induced changes in cell proliferation. TSU-pr1 epithelial cells transfected with a neomycin-resistance vector alone demonstrated a dose-dependent increase in the rate of NGF-stimulated [3H]thymidine uptake. Expression of p75NTR decreased the dose-dependent NGF-mediated proliferation of the TSU-pr1 prostate epithelial cells. The greater the degree of expression of p75NTR in the transfected clones, the less the stimulatory effect of exogenous NGF on cell proliferation. Furthermore, the ratio of p75NTR to tropomyosin receptor kinase for each clone was inversely correlated with the ability of NGF to stimulate growth of the TSU-pr1 transfectants. To determine whether p75NTR-mediated growth inhibition of prostate epithelia occurs by induction of programmed cell death, transiently transfected clones were analyzed by an in situ DNA nick-translation assay. NGF deprivation and anti-NGF treatment of transiently transfected TSU-pr1 cells significantly increased the proportion of epithelial cells undergoing programmed cell death by approximately fourfold above control levels. Conversely, addition of NGF was able to rescue p75NTR-expressing clones from undergoing programmed cell death at levels not significantly different from those of mock-transfected clones. These results demonstrate that p75NTR is a negative regulator of human prostate epithelial cell growth by induction of programmed cell death. Hence, loss of p75NTR expression in human prostate epithelia eliminates a growth-inhibitory pathway, thereby contributing to the malignant progression of the prostate.

β 1C Integrin in Epithelial Cells Correlates with a Nonproliferative Phenotype : Forced Expression of β 1C Inhibits Prostate Epithelial Cell Proliferation

The expression of the beta1C integrin, an alternatively spliced variant of the beta1 subunit, was investigated in human adult and fetal tissues. In the adult, beta1C immunoreactivity was found in nonproliferative, differentiated simple, and/or pseudostratified epithelia in prostate glands and liver bile ducts. In contrast, beta1C was undetectable in stratified squamous epithelium of the epidermis and/or in hepatocytes. Luminal prostate epithelial cells expressed beta1C in vivo and in vitro, but no beta1C was seen in basal cells, which are proliferating cells. Fetal prostate expressed beta1C in differentiated glands that had a defined lumen, but not in budding glands, indicating that beta1C is a marker of prostate epithelium differentiation. The beta1C and the common beta1A variants are differentially distributed: beta1A was found in luminal and basal epithelial as well as in stromal cells in the prostate. In the liver, beta1C and beta1A were coexpressed in biliary epithelium, whereas vascular cells expressed only beta1A. Because we found beta1C in nonproliferative and differentiated epithelium, we investigated whether beta1C could have a causal role in inhibiting epithelial cell proliferation. The results showed that exogenous expression of a beta1C, but not of a beta1A, cytoplasmic domain chimeric construct, completely inhibited thymidine incorporation in response to serum by prostate cancer epithelial cells. Consistent with these in vitro results, beta1C appeared to be downregulated in prostate glands that exhibit regenerative features in benign hyperplastic epithelium. These data show that the presence of beta1C integrins in epithelial cells correlates with a nonproliferative, differentiated phenotype and is growth inhibitory to prostate epithelial cells in vitro. These findings indicate a novel pathophysiological role for this integrin variant in epithelial cell proliferation.

Regulation of insulin-like growth factor (IGF) II and IGF binding protein 3 autocrine loop in human PC-3 prostate cancer cells by vitamin D metabolite 1,25(OH)2D3 and its analog EB1089.

Prostate cancer and benign prostate hyperplasia (BPH) are major public health problems. Prostate epithelial cell proliferation is regulated by insulin-like growth factor I (IGF-I) which is mitogenic and anti-apoptotic, and IGF binding protein 3 (IGFBP-3) which is an apoptotic agent in these cells. We demonstrate that the 1,25(OH)2D3 and its analog EB1089-induced growth inhibition was associated with increased IGFBP-3 mRNA abundance, IGFBP-3 mRNA stability, IGFBP-3 protein accumulation, and decreased IGF-II gene expression. Anti-IGF-II antibody and exogenous recombinant human IGFBP-3 inhibit PC-3 cell proliferation. The results document the inhibitory effects of 1,25(OH)2D3 and EB1089 on the IGF system of mitogens in prostate cancer cells, and suggest a potential therapeutic use of EB1089 in treatment of BPH and prostate cancer.

ROLE OF CHRONIC INFLAMMATION IN THE PROMOTION OF PROSTATIC HYPERPLASIA IN RATS

Purpose Chronic prostatitis is a common histopathological finding in prostatectomized patients. A possible interrelationship between the presence of leukocyte exudate and the extent of the hyperplastic lesions has been suggested. The aim of the present study was to analyze the effect of the immunomodulator compounds, Complete Freund Adjuvant (CFA) and cyclosporin A (CsA), administered alone or together with citral on the induction and extent of rat prostatic hyperplasia. Materials and Methods Adolescent Wistar rats (42 days old) were given citral alone or combined with CFA or CsA for one month. Semiquantitative analysis of the extent of the hyperplastic lesions was made with the histoscore protocol. Results CsA did not induce hyperplastic changes or abolish the ability of citral to promote hyperplastic changes or to affect the extent of the lymphocytic exudate in the stroma. CFA itself, however, had a proliferative action on the prostatic epithelium, and it augmented the hyperplastic changes induced by citral and even induced atypical transformations of the acinar epithelium. Conclusions Immunoinflammatory stimulators might play a role in the prostatic epithelial cell growth and proliferation processes, most probably by modulation of the cytokine system.

Insulin-like growth factors and prostate cancer.

Converging data from epidemiological and biological research implicate insulin-like growth factor (IGF) physiology in the regulation of prostate epithelial cell proliferation and in the pathophysiology of prostate cancer. This review (1) outlines elements of IGF physiology, (2) reviews recent evidence that circulating IGF-I level is related to risk of prostate cancer, (3) provides a hypothesis concerning the biological basis for the relationship between IGF-I level and risk of prostate cancer, (4) discusses IGF-I physiology in the context of neoplastic progression of prostate cancer, and (5) discusses clinical implications of these lines of research with respect to prevention and treatment.

Potentiating effect of buserelin acetate, an LHRH agonist, on the proliferation of ventral prostatic epithelial cells in testosterone-treated castrated rats.

We used buserelin acetate ([D-Ser(But)6] LHRH ), an LHRH agonist and strong blocker of LH secretion, as a treatment for prostatic cancer. It is possible that this LHRH agonist has a proliferative effect on the prostate in addition to suppressing LH secretion. The purpose of this study was to examine the proliferative effect of LHRH agonist on rat prostatic epithelial cells. We determined the optimal dose of testosterone necessary to maintain a positive level of proliferating cell nuclear antigen (PCNA) in the ventral prostatic epithelial cells of castrated Wistar rats. Testosterone-treated rats then received various doses of buserelin acetate. Castrated rats without exogenous testosterone also received buserelin acetate. The PCNA positivity was determined by immunohistochemistry with anti-PCNA monoclonal antibody. The optimal dose of testosterone enanthate was 4 mg at 0 and 28 days after castration. Administration of buserelin acetate on day 0 and 28 in doses of 0.16 mg to 1.28 mg significantly increased PCNA positivity in a dose-dependent manner. Administration of buserelin acetate to castrated rats without testosterone also increased PCNA positivity but there was no statistical significance. Buserelin acetate has a potentiating effect on the proliferation of ventral prostatic epithelial cells of castrated rat in the presence of a physiological level of exogenous testosterone. This effect may slightly influence the result of hormonal therapy by LHRH agonist.

Stromal inhibition of epithelial cell growth in the prostate; overview of an experimental study.

The paracrine influence of prostatic stroma on the proliferation of prostatic epithelial cells was investigated. Using a double-layer soft agar assay it was demonstrated that stromal cells from the human prostate inhibit the anchorage-independent growth of the prostatic tumor epithelial cell lines PC-3 and LNCaP. Anchorage-dependent growth was inhibited too as was shown in the semi-automated colorimetric MTT test performed on multiwell plates. Antiproliferative activity was mediated by a diffusible factor in the stromal cell conditioned medium and was found to be produced specifically by prostatic stromal cells. Although the putative inhibiting factor shared some properties with transforming growth factor beta (TGF-beta) evidence is presented that the factor is different from this well-known inhibitor of epithelial cell growth. Absence of TGF-beta activity was shown by the lack of inhibitory response of the TGF-beta-sensitive mink lung cell line CCL-64 to prostate stromal cell conditioned medium and to concentrated partially purified preparations of the inhibitor. Furthermore, neutralizing antibodies against TGF-beta 1 or TGF-beta 2 did not cause a decline in the level of PC-3 growth inhibition caused by partially purified inhibitor. It is concluded that the prostate stroma-derived factor may be a novel growth inhibitor different from any of the currently described inhibiting factors.

Expression of Basic Fibroblast Growth Factor, Epidermal Growth Factor, and Their Receptors in Castrated and Testosterone Injected Rat Prostates.

To examine the role of basic fibroblast growth factor (bFGF), epidermal growth factor (EGF) and their receptors in androgeninduced cell growth in the rat prostate, we divided 36 male wistar rats into 3 groups, consisting of an uncastrated and nontestosterone injected (C) group, a castrated and non-testosterone injected (CA) group, and a castrated and testosterone injected (CT) group. Each group was divided again into 2 groups and sacrificed at 4 and 8 weeks after the treatment, respectively. Injection with testosterone propionate was done subcutaneously at 4 mg/kg for a week. The epithelial cells in CT prostates exhibited much higher proliferative cell nuclear antigen (PCNA) labelling index compared with those in C prostates, and the PCNA index of the stromal cells of both groups was similar. bFGF expression increased mainly in epithelial and stromal cells in CA group. bFGF mRNA level also increased in the 4 weeks CA group. FGFR expression increased in all kind of cells of CA group, in which total FGFR mRNA level was also high. EGF immunoreactivity was intense in the proliferating epithelial cells of CT group, and EGF mRNA was also detected in the same cells. Epithelial cells in CA group were positive for EGFR, but not in CT group. However, total EGFR mRNA level increased in CT group. Taken together, bFGF synthesized by epithelial and stromal cells may participate in fibrosis and angiogenesis in the castrated rat prostates. On the other hand, androgen may induce the prostatic epithelial cell proliferation through, at least in part, autocrine or paracrine mechanism of bFGF and EGF.

Regulation and activation of focal adhesion kinase and paxillin during the adhesion, proliferation, and differentiation of prostatic epithelial cells in vitro and in vivo

Regulation and activation of focal adhesion kinase and paxillin during the adhesion, proliferation, and differentiation of prostatic epithelial cells in vitro and in vivo

Radiation inactivation and in situ renaturation of protein tyrosine kinases reveal a major 50-kDa enzyme as part of a membrane complex present in dividing but not in resting prostatic epithelial cells.

Because protein tyrosine kinases play a crucial role in the regulation of cell division and carcinogenesis, we have herein measured such enzyme activities (specific activity and subcellular distribution) and compared their characteristics with respect to hydrodynamic properties and radiation inactivation sizes as well as renaturation after electrophoresis in denaturing conditions in canine prostatic epithelial cells either in a resting (freshly isolated) or in a dividing (cultured cells) state. In quiescent cells, most protein tyrosine kinase activity was expressed by soluble proteins with a Stokes' radius (Rs) of 3.05 nm, a sedimentation coefficient (S20,w) of 4.0 S, and a molecular mass of 50 kDa. By contrast, in dividing cells (three days in primary culture), the specific activity was higher and the enzyme was mainly membrane bound. The use of a detergent (Triton X-100) allowed the extraction of most of that enzyme; its partial specific volume, S20,w and Rs were then 0.883 cm3/g, 4.0 S, and 5.6 nm, respectively, hence yielding a molecular mass of 215 kDa, which decreased to 125-145 kDa when corrected for detergent binding. Probing these chromatography-peak fractions, 50 kDa from cytosol of resting cells and 215 kDa from membrane extracts of dividing cells, with a phosphotyrosine antibody following their incubation with ATP and electrophoresis in denaturing conditions revealed the presence of a common 50-kDa phosphotyrosylated protein along with three other bands (130, 75, and 40 kDa) in the high-Mr peak of enzyme. However, the radiation inactivation size for protein tyrosine kinases expressed in both resting and dividing cells were similar, 47.2 +/- 8.7 and 44.5 +/- 6.1 kDa, respectively. Furthermore, by renaturation after electrophoresis in denaturing conditions, major protein tyrosine kinase polypeptides of 50 kDa were identified in both cell populations. Taken together, these results indicate that, in dividing prostatic epithelial cells, membrane-bound protein tyrosine kinases of low molecular weight with properties similar to those of monomeric soluble forms present in quiescent cells are part of high-molecular weight complexes. This activation process may be critical for hormone-independent proliferation of prostatic epithelial cells.

Suramin, hydrocortisone, and retinoic acid modify inhibitory effects of 1,25-dihydroxyvitamin D 3 on prostatic epithelial cells

The proliferation of prostatic epithelial cells is regulated by the complex interplay of numerous growth-stimulatory and growth-inhibitory factors. 1,25-dihydroxyvitamin D 3 [1,25(OH) 2D 3] has recently been identified as a potent inhibitor of the growth of prostatic epithelial cells. Epidemiologic studies indicate that vitamin D deficiency may be a risk factor for the development of clinical prostate cancer, possibly due to increased growth and reduced differentiation of prostatic cells in an environment with decreased 1,25(OH) 2D 3. The application of vitamin D or analogs in chemotherapy against prostate and other cancers is being explored by several investigators. In order to use vitamin D most efficaciously in a clinical setting, it may be beneficial to learn more about the interaction of 1,25(OH) 2D 3 with other factors that regulate prostatic epithelial cellular growth. In this study, we examined the effect of the proliferative status of cultured cells on their ability to respond to 1,25(OH) 2D 3, and found that minimally proliferative cells were equally as responsive to 1,25(OH)2D3 as actively dividing cells. We noted no apparent interaction of 1,25(OH) 2D 3 with epidermal growth factor, insulin-like growth factor, cholera toxin, or transforming growth factor-β, but we did find synergistic inhibitory effects of 1,25(OH) 2D 3 with suramin and retinoic acid. Perhaps most noteworthy was the dramatic increase in potency of 1,25(OH) 2D 3 that occurred upon deletion of hydrocortisone from the culture medium. Our in vitro studies indicate that combination therapy of vitamin D analogs with suramin, vitamin A analogs, or anti-glucocorticoids might be considered for prostate cancer.

Stromal inhibition of prostatic epithelial cell proliferation not mediated by transforming growth factor beta.

The paracrine influence of prostatic stroma on the proliferation of prostatic epithelial cells was investigated. Stromal cells from the human prostate have previously been shown to inhibit anchorage-dependent as well as anchorage-independent growth of the prostatic tumour epithelial cell lines PC-3 and LNCaP. Antiproliferative activity, mediated by a diffusible factor in the stromal cell conditioned medium, was found to be produced specifically by prostatic stromal cells. In the present study the characteristics of this factor were examined. It is demonstrated that prostate stroma-derived inhibiting factor is an acid- and heat-labile, dithiothreitol-sensitive protein. Although some similarities with type beta transforming growth factor (TGF-beta)-like inhibitors are apparent, evidence is presented that the factor is not identical to TGF-beta or to the TGF-beta-like factors activin and inhibin. Absence of TGF-beta activity was shown by the lack of inhibitory response of the TGF-beta-sensitive mink lung cell line CCL-64 to prostate stromal cell conditioned medium and to concentrated, partially purified preparations of the inhibitor. Furthermore, neutralising antibodies against TGF-beta 1 or TGF-beta 2 did not cause a decline in the level of PC-3 growth inhibition caused by partially purified inhibitor. Using Northern blot analyses, we excluded the involvement of inhibin or activin. It is concluded that the prostate stroma-derived factor may be a novel growth inhibitor different from any of the currently described inhibiting factors.

Expression of acid cysteine proteinase inhibitor (acpi) in the normal human prostate, benign prostatic hyperplasia and adenocarcinoma

Acid cysteine proteinase inhibitor (ACPI or cystatin A) is a protein (12 kDa) which inhibits the action of several cysteine proteinases, e.g. cathepsins B, H, L and S. In this study the cellular location of ACPI has been immunohistochemically investigated in the normal human prostate, in benign prostatic hyperplasia (BPH) and in adenocarcinoma. ACPI was found in the basal epithelial cells of the normal prostate. The secretory epithelial cells did not express ACPI. In the hyperplastic prostate, the expression of ACPI was decreased and it was also expressed more focally in the basal cells. Hyperplastic basal cells also expressed ACPI. In prostatic adenocarcinoma, no ACPI expression was found. The absence of ACPI expression was obvious and if the sections contained both benign and malignant cells, only the benign glandular structures always expressed ACPI. The results suggest that expression of ACPI might be related to prostatic epithelial cell proliferation and differentiation. Possibly the detection of ACPI in tissue sections might be helpful in identifying prostatic adenocarcinoma, especially in cases with small carcinomatous foci.

Inhibition of prostatic epithelial cell proliferation by a factor secreted specifically by prostatic stromal cells

Stromal cells from the prostate were recently shown to inhibit clonal growth of the prostatic carcinoma cell lines PC-3 (hormone-independent) and LNCaP (hormone-sensitive) in coculture. Our study revealed that stromal cell-conditioned medium strongly inhibited proliferation of PC-3 and LNCaP cells when grown in monolayer culture. Antiproliferative activity was found to be reversible, and was produced specifically by prostatic stromal cells and not by stromal cells derived from skin, foreskin, uterus, kidney, and Wilms' tumor. Inhibition was not species-specific, since the cell lines AT-2.1 and MATLyLu, derived from the Dunning rat prostate tumor, were also sensitive. No inhibition, however, occurred on breast and renal carcinoma cell lines, suggesting a prostate-specific action. The putative inhibiting factor(s) could be concentrated and partially purified by ammonium sulfate precipitation. The possible role in stromal control of epithelial cell proliferation is discussed.

Vitamin A regulates proliferation and differentiation of human prostatic epithelial cells

The response of cultured human prostatic epithelial cells to vitamin A was measured by clonal growth assay in serum-free medium. Retinoic acid at 3 nM or higher inhibited the proliferation of cell strains derived from normal, benign hyperplastic and malignant tissues, while lower levels (0.03 nM) were stimulatory. Reduced proliferation induced by retinoic acid was accompanied by a marked change in morphology, as intercellular adhesion decreased. In conjunction, the expression of keratins 8 and 18, associated with the differentiated luminal phenotype of prostatic epithelia, was increased. In post-confluent cultures, retinoic acid prevented the appearance of keratin 1, which accompanied the development of a squamous phenotype by cells maintained under these conditions. The findings of this study indicate a role for vitamin A as a modulator of the growth and differentiation of prostatic epithelial cells.

Lack of synergism among DMAB, BOP, and MNU in induction of carcinomas of the rat ventral prostate.

The present experiment was undertaken to investigate possible synergism in induction of rat prostate tumor. F344 rats were repeatedly administered the prostate carcinogens 3,2'-dimethyl-4-aminobiphenyl (DMAB),N-nitrosobis(2-oxopropyl)amine(BOP), and N-methylnitrosourea (MNU) sequentially or together at times of hormonal castration induced regenerative cell proliferation of prostate epithelial cells. Group 1 animals received two 100 mg/kg doses of DMAB, two 20 mg/kg applications of BOP, and two times 15 mg/kg of MNU. Groups 2, 3, and 4, respectively, received each of the carcinogen treatment alone. Group 5 was given 6 applications of all three in combination, each at one-third the dose administered to the other groups. The results showed a clear synergism in enhanced tumor development in the colon but not in the prostate, in which the incidence of lesions induced by the three carcinogens was similar to that with DMAB alone.

Rat prostatic growth factors: purification and characterization of high and low molecular weight epidermal growth factors from rat dorsolateral prostate

Growth factors which possibly participate in androgen-induced proliferation of rat prostate epithelial cells have been purified and characterized. Four distinct forms of growth factor were found in the extract of rat dorsolateral prostate. One of the factors was a member of heparin-binding growth factor (HBGF) family judigng from its high affinity for heparin-Sepharose. The other three factors were capable of competing with [ 125I]epidermal growth factor (EGF) for the cell surface receptor, and recognized by anti-rat EGF antiserum. These EGF-like factors (EGF1–EGF3) were purified by ion-exchange chromatography, gel filtration and reverse phase HPLC. EGF1 showed microheterogeneity on chromatographic and electrophoretic separation and N-terminal sequence analysis. EGF1 showed an average molecular weight of about 35 000 on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) under reducing conditions. These results indicated that EGF1 was a mixture of high molecular weight forms of EGF. The molecular weights of EGF2 and EGF3 were similar to that of rat submaxillary gland EGF ( M r = 5400). The amino acid sequence of EGF2 was identical with that of rat EGF except for the N- and C-terminal amino acids: aspartic acid instead of asparagine was found at the N-terminal position and C-terminal arginine was missing in EGF2. Although the N-terminal sequence of EGF3 (1–19) was identical with that of EGF2, the two factors were completely separated by gel filtration indicating a difference in the C-terminal structure. EGF1, EGF2 and EGF3 but not HBGF stimulated proliferation of primary cultured rat dorsolateral prostate epithelial cells.

In Situ Expression of mRNA for Proto-Oncogenes in Benign Prostatic Hyperplasia and in Prostatic Carcinoma

Nine cases of prostatic carcinoma and 5 cases of benign prostatic hyperplasia (BPH) were examined for the in vivo expression of mRNA by an in situ hybridization technique for cellular proto-oncogenes, c-myc, c-fos, and c-sis. The latter of which encodes the B-chain of the platelet-derived growth factor (PDGF). High levels of c-myc and c-sis mRNAs were demonstrated in one highly differentiated prostatic carcinoma. Signals were localized in epithelial cells, both in packed cancer cells and in benign hyperplastic cells with glandular differentiation. A lower level of c-fos mRNA was also detected in the same areas. Four other carcinoma specimens showed c-sis mRNA, three of which also expressed c-fos mRNA. One other carcinoma expressed only c-myc mRNA. Three BPH specimens also contained c-sis and c-fos mRNA with one also exhibiting c-myc mRNA in the glandular epithelial cells. The results support the possibility that local production of growth factors, i.e. PDGF, may play a role in proliferation of prostatic epithelial cells.

Low tumorigenic response to 3,2'-dimethyl-4-aminobiphenyl administration in the prostate of rats castrated at birth.

Six‐week‐old rats which had been orchiectomized at birth were given 3,2′‐dimethyl‐4‐aminobiphenyl (DMAB) at various doses combined with a stimulus to prostate epithelial cell proliferation in the form of oral administration of methyltestosterone (MT) for 4 weeks. Thereafter MT treatment was continued or the animals received subcutaneous implants of testosterone propionate (TP) and were maintained until sacrifice at week 60. Although prostatitis and prostatic enlargement were frequently observed, especially in the TP group, numbers of atypical hyperplastic lesions were low and only one prostatic carcinoma in situ developed. Thus, despite the presence of proliferation, castration brought about a significant reduction in susceptibility to DMAB.

106 - Role of Androgen in the Regulation of Proliferation of Rat Prostatic Stromal and Epithelial Cells in Culture

No AccessJournal of Urology1 Jun 1987Role of Androgen in the Regulation of Proliferation of Rat Prostatic Stromal and Epithelial Cells in Culture Shi-Ming Chang, Carol Bell, and Leland W.K. Chung Shi-Ming ChangShi-Ming Chang More articles by this author , Carol BellCarol Bell More articles by this author , and Leland W.K. ChungLeland W.K. Chung More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(17)75256-1AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Role of Androgen in the Regulation of Proliferation of Rat Prostatic Stromal and Epithelial Cells in Culture." The Journal of Urology, 137(6), p. 130A © 1987 by The American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 137Issue 6June 1987Page: 130A Advertisement Copyright & Permissions© 1987 by The American Urological Association Education and Research, Inc.MetricsAuthor Information Shi-Ming Chang More articles by this author Carol Bell More articles by this author Leland W.K. Chung More articles by this author Expand All Advertisement Loading ...