Molecular urology最新文献

{"title":"Effects of Unilateral Ischemia on the Contractile Response of the Bladder: Protective Effect of Tadenan (Pygeum africanum Extract).","authors":"Chen,&nbsp;Levin,&nbsp;Horan,&nbsp;Buttyan","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Recent studies indicate that localized (regional) ischemia may play an important role in the etiology of the contractile dysfunctions secondary to partial outlet obstruction. Pretreatment with Tadenan® (Pygeum africanum extract) has been shown to protect the rabbit bladder against the development of both contractile and biochemical dysfunctions induced by partial outlet obstruction, possibly by protecting the bladder against ischemic injury. The current study was designed to determine if Tadenan pretreatment of rabbits protected the bladder against the development of contractile dysfunctions induced by unilateral ischemia and to correlate effects in the presence and absence of Tadenan with the molecular response in relation to two of the most prominent genes activated by both ischemia and partial outlet obstruction: Hsp-70 and c-myc. Male New Zealand rabbits were separated into four groups of six rabbits each. Three rabbits of each group were treated for 3 weeks with Tadenan. The other three rabbits of each group were untreated controls. Each rabbit in Groups 2, 3, and 4 was anesthetized, and all major arteries entering on the right side of the bladder were li-gated. Rabbits in Group 1 were nonischemic. After 30, 60, and 120 minutes of unilateral ischemia, the rabbits in groups 2, 3, and 4, respectively, were euthanized. The bladders were removed, and contractility studies were performed on strips of detrusor muscle isolated from both the ischemia and nonischemic sides. The balance of the ischemic and nonischemic sides were frozen and stored in liquid nitrogen until analyzed for the expression of Hsp-70 and for c-myc. Tadenan pretreatment protected the nonischemic side of the bladder from the development of contractile dysfunctions, and unilateral ischemia resulted in a 10-fold increase in the expression of both Hsp-70 and c-myc in the bladders isolated from the Tadenan-treated rabbits. These results indicate that Tadenan has a protective effect against ischemic damage to the bladder. This protection may involve enhanced expression of Hsp-70 and other genetic factors.</p>","PeriodicalId":80296,"journal":{"name":"Molecular urology","volume":"3 1","pages":"5-10"},"PeriodicalIF":0.0,"publicationDate":"1999-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21695469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic Role of in Vitro Survival Efficiency in Human Transitional-Cell Carcinoma.","authors":"Özveren,&nbsp;Türker&idot;,&nbsp;Özyürek,&nbsp;Akda&scedil;","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The purpose of this study was to assess the correlation of in vitro growth features of transitional-cell carcinoma (TCC) specimens with the clinical behavior of the respective tumors. We also analyzed the impact of depth of tumor invasion, histologic differentiation, morphologic characteristics, and nuclear p53 accumulation of tumors on the in vitro survival efficiency of microtumor cultures and the significance of these factors in predicting recurrence and progression of bladder cancer. The tumor cell lines derived from surgical specimens were cultured at 37 degrees C in 5% CO(2) and constant humidity. Microtumor cultures were classified into three groups according to their in vitro lifespan. Our results indicate that higher survival efficiency implies a propensity for aggressive clinical behavior of the tumor in vivo. Factors that imply a poorer prognosis account for longer lifespans for microtumour cultures. These prognostic indicators are also associated with higher rates of recurrence and progression for tumors that exhibit higher survival efficiency in vitro.</p>","PeriodicalId":80296,"journal":{"name":"Molecular urology","volume":"3 4","pages":"349-356"},"PeriodicalIF":0.0,"publicationDate":"1999-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21695474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neoadjuvant Androgen Ablation Combined with External-Beam Radiation Therapy and Permanent Interstitial Brachytherapy Boost in Localized Prostate Cancer.","authors":"Sylvester,&nbsp;Blasko,&nbsp;Grimm,&nbsp;Meier,&nbsp;Goy,&nbsp;Colburn,&nbsp;Cavanagh","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Androgen ablation therapy has been combined with permanent interstitial brachytherapy in order to downsize the gland prior to seed implantation. It also has been employed in an attempt to improve the effectiveness of therapy in patients with a poor prognosis. We report on 50 patients consecutively treated and prospectively followed. All received neoadjuvant hormonal therapy (NHT) and 45 Gy of external-beam therapy to a limited pelvic field, followed by permanent implantation of (125)I or (103)Pd seeds. The median follow-up is 42.1 months (range 9.0-90.8 months). The prostate specific antigen (PSA) progression-free survival rate (<1.0 ng/mL) was 76% at 5 years (Kaplan-Meier method). Local control was achieved in 100% of the patients and distant disease-free survival in 85%. High-risk patients treated contemporaneously with these patients, who received external-beam radiation and a seed boost without NHT, had a 62% rate of 5-year PSA progression-free survival. Although the modest improvement in PSA progression-free survival is not statistically significant at 5 years (P = 0.5), the patients treated with NHT in addition to combined radiotherapy presented with significantly higher serum PSA concentrations (mean 21.0 ng/mL; median 17.0 ng/mL) than those treated with combination radiotherapy alone (mean 15.6 ng/mL; median 10.6 ng/mL) and thus had a worse prognosis.</p>","PeriodicalId":80296,"journal":{"name":"Molecular urology","volume":"3 3","pages":"231-236"},"PeriodicalIF":0.0,"publicationDate":"1999-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21695785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathophysiology of Erectile Dysfunction.","authors":"Melman,&nbsp;Rehman","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Physiology of erection and pathophysiology erectile dysfunction is reviewed. Analysis is obtained from basic and clinical research including animals studies, anatomical studies, and molecular and cellular research on corporal tissue obtained during penile prosthesis implantation. Supraspinal influences and spinal influence on penile erection has been learned from spinal cord injury patient. Corporal smooth muscle relaxation of penile arteries and corpus cavernosum leads to penile erection, results from parasympathetic/nonadrenergic noncholinergic neural pathway activation and simultaneous inhibition of sympathetic outflow. Anatomical studies taught understanding of the mechanism for restriction of blood outflow from the corpora cavernosa. The change of smooth muscle tone has emerged as a key factor in erection and detumescence. Many independent factors converge on the modulation of corporal smooth muscle tone. Neuronal and local neurotransmitter effects via gap junction, potassium channels, and calcium channel. A nitric oxide/cyclic guanosine monophosphate mechanism as well as cyclic aminomonophosphate has an important role in mediating the corporal smooth muscle relaxation necessary for erectile function. Erectile dysfunction can be due to vasculogenic, neurogenic, hormonal, veno-occlusive, psychogenic and/or pharmacogenic factors as well as alterations in the nitric oxide/cyclic guanosine monophosphate (cGMP) or cyclic aminophosphate (cAMP) pathway or other regulatory mechanisms including gap junction or ionic channel resulting in an imbalance in corporal smooth muscle contraction and relaxation. Our present knowledge of the hemodynamics, functional anatomy, neurophysiology, and neuropharmacology of penile erection and dysfunction at the cellular and molecular level has led to better understanding of physiology and pathophysiology of erectile dysfunction.</p>","PeriodicalId":80296,"journal":{"name":"Molecular urology","volume":"3 2","pages":"87-102"},"PeriodicalIF":0.0,"publicationDate":"1999-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21694705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of Transforming Growth Factor-beta Receptors and Related Cell-Cycle Components in Transitional-Cell Carcinoma of the Bladder.","authors":"McGarvey,&nbsp;Tait,&nbsp;Tomaszewski,&nbsp;Malkowicz","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Exogenous transforming growth factor-beta (TGF-beta) is a potent inhibitor of normal epithelial cell growth but does not generally inhibit the growth of cell lines of transitional-cell carcinoma (TCC) of the bladder. In addition, a lack of the TGF-beta2 transcript and a marked reduction of the TGF-beta1 transcript have been reported in some high-stage TCCs. The purpose of this investigation was to examine the steady-state expression of TGF-beta receptor I and TGF-beta receptor II and a downstream target, p27(KIP1), as well as cyclin E in normal bladder and superficial and invasive TCC in order to better understand the role of TGF-beta downstream targets in TCC insensitivity to TGF-beta. Quantitative RT-PCR was employed to study the expression of TGF-beta receptor I and receptor II. p27(KIP1), and cyclin E in normal bladder and superficial and invasive TCC lesions. Steady-state levels of p27(KIP1), TGF-beta receptors, and cyclin E mRNAs were similar in superficial TCC samples and normal bladder mucosa. There was a significant decrease in p27(KIP1) and TGF-beta receptor II mRNA expression in invasive lesions compared with superficial tumors (P < 0.004; P < 0.02). In contrast, there was no significant difference in the expression of TGF-beta receptor I mRNA between normal bladder and superficial and invasive TCC. There was a significant increase in the expression of cyclin E mRNA in invasive TCC compared with superficial TCC or normal bladder (P < 0.015). These results suggest that aberrant expression of these genes contributes to the phenotype of invasive bladder cancer.</p>","PeriodicalId":80296,"journal":{"name":"Molecular urology","volume":"3 4","pages":"371-380"},"PeriodicalIF":0.0,"publicationDate":"1999-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21694786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rehabilitation of the Impotent Patient: An Update.","authors":"Steers","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Erectile dysfunction (ED) affects as many as 90% of patients after treatment for prostate cancer. Denervation appears to be the primary mechanism after either surgery or radiation; venooclusion or smooth-muscle dysfunction may follow. There may also be a vasculogenic component. Changes in surgical technique and pharmacologic prophylaxis may reduce the likelihood of ED. In men who desire reversal of ED, a stepwise approach beginning with oral sildenafil and, if that drug is ineffective, moving to intraurethral or intracavernous therapy and, finally, to a surgical approach is advisable.</p>","PeriodicalId":80296,"journal":{"name":"Molecular urology","volume":"3 3","pages":"323-326"},"PeriodicalIF":0.0,"publicationDate":"1999-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21695126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulatory Issues in Prostate Cancer Studies.","authors":"Fourcroy","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Quality of life and informed consent are two of the important issues for designers of clinical trials. The former has physical, psychological, economic, and social components. Investigators must understand the features of the various measurement instruments and select one that is appropriate to the circumstances. It also is necessary to identify what changes are significant. Statistical significance is not identical to clinical significance. Ethical guidelines for the protection of human subjects is another important issue. Information on regulations is available on many Web sites, including that of the Food and Drug Administration.</p>","PeriodicalId":80296,"journal":{"name":"Molecular urology","volume":"3 3","pages":"329-332"},"PeriodicalIF":0.0,"publicationDate":"1999-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21695127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ion Channels and Gap Junctions: Their Role in Erectile Physiology, Dysfunction, and Future Therapy.","authors":"Christ,&nbsp;Wang,&nbsp;Venkateswarlu,&nbsp;Zhao,&nbsp;Day","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>A flurry of research and clinical activity during this past decade has documented that the tonicity and synchronicity of the corporal smooth muscle cells of the penis are major determinants of erectile capacity and function. Specifically, the effects of diverse and bifurcating intracellular signal transduction pathways on the activity of nonjunctional ion channels such as potassium (K(+)), calcium (Ca(2+)), and chloride (C(1-)) govern the former, whereas intercellular communication through gap junctions provides the anatomic substrate for the latter. Recent studies at the tissue, cellular, subcellular, and molecular levels have verified this supposition and provided important insight into how subtle alterations in the balance between contraction and relaxation of the corporal smooth muscle cells can predispose a man to erectile failure. This report reviews the available information concerning the participation of gap junctions and K(+), Ca(2+), and C(1-) channels in the erectile process and describes their importance as potential molecular targets for the future therapy of erectile dysfunction (ED). It is argued that a major goal should now be to proceed on at least two fronts simultaneously: (1) to capitalize on these new mechanistic insights by developing novel treatments for ED centered on the modulation of ion channel activity; and (2) simultaneously to take advantage of the unique therapeutic opportunities afforded by the presence and ubiquitous distribution of gap junction channels in the human corpora. One strategy that fulfils both criteria will be briefly reviewed, that is, gene therapy with the maxi-K(+) channel subtype.</p>","PeriodicalId":80296,"journal":{"name":"Molecular urology","volume":"3 2","pages":"61-73"},"PeriodicalIF":0.0,"publicationDate":"1999-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21694702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Andorgens in the Erectile Response: A 1999 Perspective.","authors":"Mills,&nbsp;Lewis","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Evidence from several laboratories strongly supports a critical role for androgens in the maintenance of the mammalian erectile response. In animal studies, androgens appear to act at the end-organ level (i.e., corporal tissue and vasculature), as well as in the portions of the nervous system which mediate erection. Particularly in the rat model, androgens act centrally to support copulatory behavior and peripherally to maintain the production of nitric oxide and support the veno-occlusive mechanisms. Other studies suggest that alternative, non-NO-dependent, pathways may also be androgen sensitive. However, despite this expanding knowledge base about how androgens act in the erectile response in laboratory animals, the recent studies have not greatly clarified the role of androgens in human penile erection. There does not seem to be a strong cause and effect relation between blood androgen concentrations and erectile function; even in severely hypogonadal men, the erectile response is not always lost, and testosterone treatment of hypogonadal men with erectile dysfunction does not necessarily restore lost erectile function. In addition, different types of erection (nocturnal, in response to visual sexual stimulation, in response to sexual partner) may require different degrees of androgenic support.</p>","PeriodicalId":80296,"journal":{"name":"Molecular urology","volume":"3 2","pages":"75-86"},"PeriodicalIF":0.0,"publicationDate":"1999-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21694703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism of Brefeldin A-Induced Growth Inhibition and Cell Death in Human Prostatic Carcinoma Cells.","authors":"Chapman,&nbsp;Tazaki,&nbsp;Mallouh,&nbsp;Konno","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The mechanism of growth inhibition and triggering of cell death by the antibiotic brefeldin A (BFA) was investigated in human prostatic cancer DU-145 cells. After cells were cultured with various concentrations of BFA, cell number and viability were determined at specified times. Compared with untreated cells, a drastic growth reduction (>80%) with approximately 50% cell death was observed in the cells cultured with BFA (30 ng/mL) for 72 h. Cell-cycle analysis using flow cytometry revealed that such growth inhibition was associated with approximately 85% reduction in the S-phase population, indicating the inhibition of the G(1)-S phase progression. Western blots further showed that cell-cycle-dependent kinases (cdk2 and cdk4), cyclin D(1), and p53 were all downregulated, whereas WAF1 (p21) was upregulated with BFA treatment. Possible induction of apoptosis by BFA was also assessed by TUNEL assay and by DNA analysis using agarose gel electrophoresis. The TUNEL assay demonstrated the positive staining of BFA-treated cells, and gel electrophoresis confirmed nucleosomal DNA ladder formation. Thus, these results suggest that growth inhibition of DU-145 cells by BFA is attributable mainly to a G1 cell-cycle arrest through the modulation of specific cell-cycle regulators. The accompanying cell death may follow a p53-independent apoptotic pathway.</p>","PeriodicalId":80296,"journal":{"name":"Molecular urology","volume":"3 1","pages":"11-16"},"PeriodicalIF":0.0,"publicationDate":"1999-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21695470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}