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Biomedical subjects

A Shabsigh

Publications and source records attributed to A Shabsigh.

At least 19 recordsLinked to original sources
PubMed2004

Preventing reservoir calculi after augmentation cystoplasty and continent urinary diversion: the influence of an irrigation protocol.

OBJECTIVE: To evaluate the influence of an irrigation protocol in preventing reservoir calculi forming after augmentation cystoplasty and continent urinary diversion. PATIENTS AND METHODS: Between 1985 and 1995, 91 patients had an augmentation cystoplasty and/or continent urinary diversion (group 1; 54 females and 37 males, mean age 11.1 years, range 1-31); these patients were not routinely instructed to use irrigation after surgery. The segments used included ileum (44), colon (36), stomach (eight) and ureter (three). Between 1995 and 2000, 42 patients (group 2) underwent urinary reconstruction (22 females and 20 males, mean age 14.8 years, range 4-27), the segment used being ileum (30), colon (five), ureter (five) and stomach (two) but in contrast to group 1 they then were placed on a standard prophylactic irrigation protocol. The occurrence of stones in the reservoir was then assessed. RESULTS: Thirty-nine of the 91 patients (42.8%) in group 1 presented with reservoir calculi after reconstruction and 22 had several episodes. The mean time to presentation was 30 months. The incidence of stone formation by underlying diagnosis included: myelomeningocele, 32/48 (66%), exstrophy five/25 (25%), posterior urethral valves two/20 (10%) and rhabdomyosarcoma, none of three. Fifty of the 91 patients had an abdominal stoma, with stone formation in 33 (66%), while 41 used the native urethra, with stone formation in six (15%). Three (7%) of the 42 patients in group 2 developed reservoir calculi after reconstruction, two in patients with myelomeningocele and one in a trauma patient who had residual bone spicules in the bladder; the mean time to presentation was 26.5 months. CONCLUSIONS: These data suggest that the irrigation protocol used in group 2 significantly reduced the number of reservoir calculi after urinary tract reconstruction when bowel was used as part of the reconstruction (43% vs. 7%). The most calculi in both groups were in immobile patients with sensory impairment. Also, patients with an abdominal stoma had a greater risk of reservoir calculi (66%) than those using the native urethra (15%).

Adolescent↗
PubMed2001

Reduction of wild type p53 function confers a hormone resistant phenotype on LNCaP prostate cancer cells.

BACKGROUND: The protein encoded by the p53 gene is required for some forms of apoptosis and loss or mutations in this gene are found with increased frequency in advanced and hormone resistant human prostate cancers. In order to better appreciate whether reduction of wildtype p53 function in prostate cancer cells might contribute to the development of therapeutic-resistance by these cells, we created stable variants of the androgen-responsive, wild type p53-expressing human prostate cancer cell line, LNCaP, by transfection with expression vectors designed to reduce expression or function of wildtype p53 in them. These cells were then tested for their ability to form tumors in castrated male nude mice. METHODS: A conditional eukaryotic expression vector (under tetracycline regulation) expressing antisense p53 cDNA was constructed and either directly transfected into LNCaP cells or tranduced into these cells using recombinant retroviruses containing the vector. Stably transfected/transduced cells (LNCaP/Asp53) were evaluated by Western blot analysis for the ability of doxycycline to reduce p53 protein expression and for their ability to form tumors in castrated male nude mice treated or untreated with doxycycline. Additionally, we derived an LNCaP subline (LNCaP/DD) stably expressing a dominant-negative form of p53 and tested these cells for their ability to form tumors in castrated male nude mice. RESULTS: LNCaP/Asp53 cells showed reduced expression of p53 protein when cultured in a medium containing doxycycline and tested sublines were able to efficiently form tumors in castrated male nude mice only when the mice were treated with doxycycline. LNCaP/DD cells were readily able to form tumors in castrated male nude mice whereas parental LNCaP cells or control-transfected LNCaP cells were not. CONCLUSION: Loss of wildtype p53 function can contribute to the phenotype of hormone resistance of prostate cancer cells.

Animals↗
PubMed2001

Erectile dysfunction is a marker for cardiovascular complications and psychological functioning in men with hypertension.

The aim of this study was to investigate the incidence of cardiovascular complications in hypertensive patients with erectile dysfunction (ED). An anonymous questionnaire was mailed to 467 and received from 104 hypertensive male patients. Despite the low response rate of 22%, the following interesting findings could be observed: 70.6% of the patients who responded suffered from ED. The hypertensive patients with ED had significantly higher prevalence of cardiovascular complications (P < 0.05). The correlation between depression and low quality of life as well as between ED and low sexual satisfaction was also statistically significant (P = 0.05). ED in hypertensive patients can be considered as a marker for cardiovascular complications in this patient group.

Adult↗
PubMed2001

Biomarker analysis demonstrates a hypoxic environment in the castrated rat ventral prostate gland.

Within the first 24 h after castration of an adult male rat, the vascular system of the ventral prostate gland undergoes a degenerative process that drastically reduces blood flow to the tissue. Since the vascular degeneration precedes the loss of the prostatic epithelium (by apoptosis), we have proposed that the onset of epithelial cell apoptosis in this tissue is caused by an ischemic/hypoxic environment resulting from the loss of blood flow. In order to further evaluate the extent to which ischemia/hypoxia might be a factor in apoptosis of the prostate epithelium after castration, we analyzed for biomarkers of cellular hypoxia in rat ventral prostates during the first 3 days following castration. Ventral prostate tissues removed from hypoxyprobe-1-treated adult male rats (uncastrated controls; surgically castrated for 24, 48 or 72 h, or sham-castrated for equivalent times) were directly analyzed for evidence of hypoxia by in situ immunohistochemical evaluation of hypoxyprobe-1 adduct formation in the prostate cells. Protein extracts from these tissues were also tested for expression of the 120 kDa hypoxia-inducible factor-1-alpha (HIF-1-alpha) protein as well as for expression of mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) proteins using a Western blot assay. The tyrosine phosphorylation status of the latter signaling molecules was also evaluated by Western blotting using anti-tyrosine phosphate antibodies. Our results showed that epithelial cells of the rat ventral prostate stained positively for hypoxyprobe-1 adducts at all times after castration, whereas cells in control tissues were unstained by this procedure. In addition, the prostatic expression of HIF-1-alpha protein was increased approximately 20-fold at 48 h after castration compared to control tissues. Finally, although prostatic MAPK and JNK protein expression was unaltered during the early period after castration, phosphorylation of the JUN kinase protein was significantly elevated, indicating that this stress-activated cellular signaling pathway becomes more active subsequent to castration. These results support our proposal that early castration-induced degeneration and constriction of the vascular system of the rat ventral prostate gland leads to reduced oxygenation of prostatic epithelial cells and the activation of hypoxic cellular signaling in these cells through upregulation of HIF-1-alpha expression and stimulation of the JUN kinase signaling pathway.

Animals↗
PubMed2000

Prostatic neoplasia in transgenic mice with prostate-directed overexpression of the c-myc oncoprotein.

BACKGROUND: Promoter elements within the 5' DNA region of the rat C(3)1 gene have been shown to direct prostate-specific expression of gene products when they are fused through recombinant DNA procedures and used to produce transgenic mice. In order to test the in vivo effects of chronic overexpression of the mouse c-myc protooncogene on the prostate glands of transgenic mice, we created several lines of C(3)1-c-myc transgenic mice and then examined the phenotype of males with this genetic alteration. METHODS: The modified promoter and 5' region of the rat C(3)1 gene was fused to the coding region of the mouse c-myc gene using recombinant DNA techniques. This DNA was used to create three different founder lines of transgenic mice. Tissues from males and females heterozygous for the transgene were examined for expression of the recombinant mouse c-myc mRNA by an RNase protection assay. Prostates from males were examined for expression of recombinant c-myc mRNA by in situ hybridization. Thin sections of fixed ventral prostates from males were analyzed by microscopy for histological abnormalities. RESULTS: Three different lines of transgenic mice were obtained from these procedures. These mice demonstrated expression of recombinant mouse c-myc mRNA in the testis and ventral prostates of males and in the uterus of females. In situ hybridization demonstrated that the epithelial cells were the source of recombinant c-myc expression in the ventral prostates of the transgenic lines. Microscopic analysis of the ventral prostates from these mice demonstrated abnormalities in epithelial cell morphology seemingly typical of an intraepithelial neoplasia-like phenotype. However, none of the males of any of the lines developed overt prostatic adenocarcinoma over their lifetimes. CONCLUSIONS: Chronic overexpression of c-myc in the ventral prostate epithelial cells of C3(1)-c-myc transgenic mice leads to the development of epithelial cell abnormalities similar to those seen in low-grade prostatic intraepithelial neoplasia in humans. These abnormalities were not found to progress to adenocarcinoma over the lifetimes of the transgenic mice, suggesting the need for additional oncogenic changes in the pathway to prostatic adenocarcinomas. Furthermore, our cumulative experience with the use of the C3(1) gene promoter in the generation of transgenic mice suggests that the probasin promoter element provides a much more specific and effective means to target transgenes to the prostate glands of mice.

Animals↗
PubMed2000

Vascular endothelial growth factor-A expression in the rat ventral prostate gland and the early effects of castration.

BACKGROUND: Blood flow to the rat ventral prostate gland is drastically reduced during the very early period after castration, and this reduction coincides with the appearance of striking degenerative changes within the prostatic vascular system. These early effects on the prostate vascular system are likely to be important for the subsequent regression of the ventral prostate that occurs in response to castration. Since the endothelial cells of the ventral prostate do not express androgen receptor protein (AR), we proposed that these early effects might be indirectly mediated by changes in the local expression of vascular regulatory factors. In order to evaluate whether vascular endothelial growth factor-A (VEGF-A) might be among the primary mediators of these effects, we measured expression of VEGF-A mRNA and protein in the rat ventral prostate gland prior to and within the first 3 days after castration. METHODS: Ventral prostate tissues were obtained from control (unoperated) rats, sham-operated rats, or rats at sequential daily intervals (1-3 days) after castration. A quantitative RNase protection assay and a comparative RT-PCR assay were used to evaluate the extent to which the expression of VEGF-A mRNA in the ventral prostate was affected by castration. In situ immunohistochemistry, using an anti-VEGF-A antibody, was performed to localize VEGF-A protein in the various cells of the tissue. Western blot analysis and a quantitative ELISA assay using anti-VEGF-A antibodies were performed to determine how VEGF-A protein expression in the rat ventral prostate was affected by castration. RESULTS: Results of VEGF-A mRNA analysis in the rat ventral prostate gland during the first 3 days after castration showed a biphasic change characterized by a transient reduction of VEGF-A mRNA expression (by approximately 50%) on the second day after castration that was restored to higher than control levels by the third day after castration. Immunohistochemical analysis for VEGF-A in control and castrated ventral prostates showed that the prostatic epithelial and smooth muscle cells were the major source of VEGF-A expression in this tissue. Quantitative analysis of VEGF-A protein expression by Western blot and ELISA methods confirmed a biphasic change in the expression of the polypeptide that correlated well with the results of the mRNA analyses. CONCLUSIONS: VEGF-A expression in the ventral prostate gland of the Sprague-Dawley rat is downregulated on the second day after castration but returns to control levels by the third day after castration. Since critical changes in the ventral prostate vascular system are already evident by 1 day after castration, we believe that these findings indicate that VEGF-A is not likely to be the critical or sole mediator of the early effects of castration on the vascular system of the rat ventral prostate gland.

Androgens↗
PubMed2000

Acute increase in blood flow to the rat bladder subsequent to partial bladder outlet obstruction.

Partial obstruction of the rat bladder outlet initiates a multi-step process during which the bladder progressively loses its functional ability. The first step in this progression is bladder hypertrophy; the organ dramatically increases in size and weight to compensate for the effects of obstruction. Unoperated female rats, age-matched, sham-obstructed rats, and rats that received a partial bladder outlet obstruction were studied. During the first 24 hours after partial bladder outlet obstruction, relative bladder blood flow was measured using a fluorescent microsphere infusion technique and laser Doppler imaging. Nitric oxide synthase (NOS) activities of control and obstructed rat bladder tissues were determined using an enzymatic assay that measures the conversion of (3)H-L-arginine to (3)H-L-citrulline. Using the microsphere infusion technique, a significant increase in blood flow to the obstructed rat bladder was observed during the first 24 hours after partial bladder outlet obstruction. Relative bladder blood flow increased approximately sixfold at 4 and 6 hours post-obstruction and remained elevated through 24 hours of obstruction. Sham operations (evaluated after 6 hours after surgery) resulted in a minor increase in blood flow that did not reach statistical significance. Relative blood flow to the spleen, measured in the same rats, was not significantly changed. Laser Doppler measurements also identified a significant increase in rat bladder blood flow after outlet obstruction and showed that increased blood flow could be detected as early as 1 hour post-obstruction. Interestingly, despite the significant differences in bladder blood flow between control and early post-obstructed rat bladders, NOS activities of control and obstructed rat bladders were comparable. The increase in bladder blood flow precedes the urothelial, fibroblast and smooth muscle cell hyperplasia, and the smooth muscle hypertrophy that occurs after obstruction. We propose that, in response to surgical induction of partial outlet obstruction, acute up-regulation of bladder blood flow may be an initiating factor for subsequent bladder cell proliferation and smooth muscle hypertrophy. Neurourol. Urodynam. 19:195-208, 2000.

Animals↗
PubMed2000

Cryoablation for clinically localized prostate cancer using an argon-based system: complication rates and biochemical recurrence.

OBJECTIVE: To determine the complication rates and biochemical recurrence after cryoablation of the prostate, using an argon gas-based system, in patients with localized prostate cancer. PATIENTS AND METHODS: Between October 1997 and June 1999, 35 patients underwent cryoablation of the prostate (19 after radiation therapy failure and 16 as a primary treatment for localized prostate cancer). All patients had biopsy-confirmed prostate cancer with no seminal vesicle invasion, negative bone scans and a negative lymph node dissection. Patients received 3 months of combined hormonal therapy before cryosurgery. One surgeon performed all the procedures. Biochemical recurrence was defined by an increase in prostate specific antigen (PSA) of >/= 0.2 ng/mL above the PSA nadir. RESULTS: The complications were rectal pain (26%), urinary infection (3%), scrotal oedema (12%), haematuria (6%) and incontinence (6%). Complication rates were higher in those patients who failed after radiation therapy than in those who did not receive radiation (incontinence 11% vs 0%, rectal pain 37% vs 12%) but the difference was not statistically significant. Twenty-two patients (63%) had an undetectable serum PSA nadir (< 0.1 ng/mL) after cryotherapy and 30 (84%) patients had a PSA value of < 1.0 ng/mL. After a mean follow-up of 8.3 months (range 0.2-18), nine patients had biochemical recurrence. The biochemical recurrence-free survival (BRFS) was 70% at 9 months. Patients who had an undetectable PSA nadir had a statistically higher BRSF at 9 months than did patients who had a detectable PSA nadir (89% vs 55%, respectively, P = 0.03). Similarly, patients with a preoperative serum PSA level of < 10 ng/mL had a statistically higher BRFS than patients who had a PSA level of > 10 ng/mL (86% vs 42% at 9 months, P < 0.001). CONCLUSION: A PSA level before cryotherapy of < 10 ng/mL and an undetectable PSA nadir after cryotherapy were associated with the highest BRFS. Cryoablation of the prostate, with low morbidity, seems to be a viable option in managing patients by salvage therapy after radiation therapy and for the primary treatment of clinically localized prostate cancer.

Adult↗
PubMed2000

Herbal therapy PC-SPES: in vitro effects and evaluation of its efficacy in 69 patients with prostate cancer.

PURPOSE: We investigate the potential use of the phytotherapeutic PC-SPES to treat human prostate cancer, and evaluate its in vivo and in vitro activity, and clinical efficacy. MATERIALS AND METHODS: PC-SPES was evaluated for its ability to induce apoptosis on prostate cancer cell lines LNCaP, PC3 and DU145. The effect of oral PC-SPES on growth of PC3 tumors present in male immunodeficient mice was studied. A total of 30 male nude mice were divided in 5 groups. In groups 1 control and 2 full dose therapy was started the same day of the tumor injection. In groups 3 control, 4 half dose and 5 full dose PC-SPES therapy was initiated 1 week after tumor injection. A total of 69 patients with prostate cancer were treated with 3 capsules of 320 mg. PC-SPES daily. Serum prostate specific antigen (PSA) responses and side effects were evaluated. RESULTS: All of the cultured prostate cancer cell lines had a significant dose dependent induction of apoptosis following exposure to an alcoholic PC-SPES extract. Immunodeficient mice xenografted with the PC3 cell line had reduced tumor volume compared with sham treated controls when they were treated with a PC-SPES extract from the time of tumor cell implantation (931 +/- 89 versus 1,424 +/- 685 mm.3, p not significant) but not when the treatment was begun 1 week after tumor cell implantation. The testis, prostate, bladder and seminal vesicles of the treated mice were significantly reduced in weight compared with the sham treated animals. Of the patients with prostate cancer 82% had decreased serum PSA 2 months, 78% 6 months and 88% 12 months after treatment with PC-SPES. Side effects in the treated patient population included nipple tenderness in 42% and phlebitis requiring heparinization in 2%. CONCLUSIONS: An extract of the phytotherapeutic agent PC-SPES proved to be active in inducing apoptosis of hormone sensitive and insensitive prostate cancer cells in vitro, and in suppressing the growth rate of a hormone insensitive prostate cancer cell line in vivo. The overwhelming majority of patients with prostate cancer treated with the agent experienced a decrease in serum PSA but also demonstrated a side effect profile comparable to estrogen treatment.

Aged↗
PubMed2000

The effects of androgen deprivation on the prostate gland: cell death mediated by vascular regression.

Androgenic steroids are required to maintain the prostate gland in the adult state. Consistent with this requirement, androgen deprivation therapies typically induce a drastic regression of mature prostate tissue that is accompanied by the extensive loss of prostate cells through the programmed cell death process referred to as apoptosis. Whereas, in the past, the loss of prostate cells associated with androgen deprivation has generally been perceived to be a direct response of the androgen receptor-expressing prostate cells to an androgen-depleted environment, more recent studies of the prostate regression process suggest that it might instead be initiated by an indirect response of the prostatic parenchyma to an ischemic/hypoxic environment caused by a drastic reduction of blood flow to the tissue that occurs when androgens are withdrawn. This article reviews evidence that the prostatic vascular system is a primary target of androgen action and other evidence suggesting that the regression of the prostate parenchyma occurs secondarily to the regression of the prostate vascular system through cell death mediated by tissue ischemia/hypoxia.

Androgen Antagonists↗
PubMed2000

Current concepts in biomarker technology for bladder cancers.

BACKGROUND: Transitional cell carcinoma of the bladder (TCC) is the second most common malignancy of the urinary tract. More than 70% of treated tumors recur, and 30% of recurrent tumors progress. Currently, pathologic staging and grading are valuable prognostic factors for detecting and monitoring TCC. Urinalysis, cystoscopy, and cytology are either invasive or lack sensitivity and specificity. The availability of a noninvasive, reliable, and simple test would greatly improve the detection and monitoring of patients with TCC. Several biomarkers for bladder cancer have been proposed, but no single marker has emerged as the test of choice. APPROACH: We undertook a comprehensive literature search using Medline to identify all publications from 1980 to 1999. Articles that discussed potential biomarkers for TCC were screened. Only compounds that demonstrated high sensitivity or specificity, significant correlation with TCC diagnosis and staging, and extensive investigation were included in this review. CONTENT: Potential biomarkers of disease progression and prognosis include nuclear matrix protein, fibrin/fibrinogen product, bladder tumor antigen, blood group-related antigens, tumor-associated antigens, proliferating antigens, oncogenes, growth factors, cell adhesion molecules, and cell cycle regulatory proteins. The properties of the biomarkers and the methods for detecting or quantifying them are presented. Their sensitivities and specificities for detecting and monitoring disease were 54-100% and 61-97%, respectively, compared with 20-40% and 90% for urinalysis and cytology. SUMMARY: Although urine cytology and cystoscopy are still the standard of practice, many candidate biomarkers for TCC are emerging and being adopted into clinical practice. Further research and better understanding of the biology of bladder cancer, improved diagnostic techniques, and standardized interpretation are essential steps to develop reliable biomarkers. It is possible that using the current biomarkers as an adjuvant modality will improve our ability to diagnose and monitor bladder cancer.

Biomarkers, Tumor↗
PubMed2000

Hypertension is associated with severe erectile dysfunction.

PURPOSE: The prevalence and severity of erectile dysfunction in patients with hypertension need to be further evaluated. We evaluate medical and hypertension status, and erectile function in patients with hypertension. MATERIALS AND METHODS: The International Index of Erectile Function, which is a detailed questionnaire, including well established components to evaluate patient medical history, hypertension status and erectile dysfunction, was mailed to 476 male patients of the outpatient Hypertension Center of Columbia Presbyterian Medical Center. RESULTS: The questionnaire was completed by 104 (22.3%) patients, and mean age was 62.2 years (range 34 to 75). Of the patients 84.8% were sexually active and 68. 3% had various degrees of erectile dysfunction, which was mild in 7. 7%, moderate in 15.4% and severe in 45.2%. Compared to the general population of erectile dysfunction cases in the literature our study population with hypertension had a higher incidence of severe erectile dysfunction. Although correlations of antihypertensive medications with incidence of erectile dysfunction did not reach statistical significance, there was a clear trend with patients treated with diuretics and beta-blockers having the highest incidence and those treated with alpha-blockers having the lowest incidence of erectile dysfunction. CONCLUSIONS: In addition to the observation that erectile dysfunction is more prevalent in patients with hypertension than in an age matched general population, our study shows that it is more severe in those with hypertension than in the general population.

Adolescent↗
PubMed2000

Reduction of endothelial and smooth muscle density in the corpora cavernosa of the streptozotocin induced diabetic rat.

PURPOSE: Erectile dysfunction is one of the most prevalent complications of diabetes in males. Because adequate vascular perfusion is needed for appropriate erectile tissue function a likely reason for the high incidence of this complication in diabetics is a pathological change associated with the disease in vascularization of erectile tissues. We investigate whether chronic diabetes may induce changes in vascularization of the corpora cavernosa using a computerized image analysis system to quantify changes in the smooth muscle and endothelial cell content of the corpora cavernosa of diabetic rats induced by streptozotocin 6 months previously, and compare these changes to those associated with aging. MATERIALS AND METHODS: We studied 3 groups of rats, including 10-week-old untreated controls, diabetic rats treated with streptozotocin for 6 months starting at age 10 weeks and 18-month-old rats (aged). Penile shafts from these groups were excised, fixed, sectioned and immunostained with anti-smooth muscle actin to identify smooth muscle cells and anti-CD31 to identify endothelial cells. Computerized image analysis was used to quantify the percent area within the corpora cavernosa occupied by smooth muscle cells or endothelial cells, and the data were compared among the groups. RESULTS: We identified a highly significant decrease in the percentage of smooth muscle and endothelial cells within the cavernosa areas of diabetic rats compared to control or aged rats. Mean cavernous smooth muscle cell content was 15.28 +/- 2.54% in control rats and 9.83 +/- 1.21% in diabetic rats (p = 0.0001). Likewise, cavernous endothelial cell content was 6.93 +/- 0.86% in the control group and 4.01 +/- 1.08% in the diabetic group (p = 0. 0001). However, no statistical difference of smooth muscle or endothelial cell content was found between control and aged rats. CONCLUSIONS: Using the streptozotocin treated rat as a model for diabetes, we showed that smooth muscle and endothelial cell density is significantly decreased in diabetic corpora cavernosa but not in normal aged rats. This observation is a further step toward the understanding of the pathomechanisms for diabetic related erectile dysfunction.

Animals↗
PubMed1999

Vascular anatomy of the rat ventral prostate.

The rat ventral prostate gland is a model tissue to study the effects of androgenic steroids on prostate cells. Recent reports suggest that the prostatic vascular system is a primary target of androgen action in this tissue. In order to better understand how the vascular system of the ventral prostate supports the tissue in an androgenically normal adult male rat we utilized a variety of microscopic imaging techniques to more fully characterize its structural anatomy and its interaction with other prostatic cell types. Vascular corrosion casts were produced from the mature ventral prostate glands of rats. These casts were analyzed by scanning electron microscopy (SEM) to describe gross and fine details of the prostate vascular anatomy. Fixed thin sections of ventral prostates were immunostained with antiFactor XIII and analyzed by light microscopy for the presence of capillary elements within the prostatic glands. Other sections were directly analyzed by transmission electron microscopy (TEM) to describe the anatomical relationship between the capillaries and the prostatic ducts and their associated glands. The rat ventral prostate is supplied with blood by branches of the inferior vesical artery which enters the apex of the tissue from the base of the urinary bladder. Visualization of the prostatic vascular network under SEM shows that this major vessel is found on the posterior-medial surface of the tissue (closest to the bladder). This surface also has numerous serpentine vessels that appear to facilitate a stable blood supply to the prostate in accommodation of urinary bladder distension. Examination of the opposing surface of the casts allowed a crude description of the structure of the prostatic ductal system with the distal tips of the ducts (containing the prostate glands) oriented towards the anterior-lateral surface of the tissue. On this surface, one can discern a series of adjacent basket-shaped vascular structures of distributing arterioles that supply a dense complex of fine capillaries to the glands. Analysis of the interface of the prostatic ductal system with its vascular elements by light microscopy and TEM shows that some capillaries lie immediately adjacent to the basement membranes of the glands while others can be found interspersed within the myofibroblast layer surrounding the ducts and glands. Veins accompany the arteries and combine with the superior vesical before entering the common iliac vein. This study gives a comprehensive and detailed view of the microvasculature of the rat ventral prostate gland. The findings here will provide the basis for future experiments to evaluate how the ventral prostate vascular system changes in response to androgenic manipulation and to other pathological conditions.

Animals↗
PubMed1999

A recombinant defective adenoviral agent expressing anti-bcl-2 ribozyme promotes apoptosis of bcl-2-expressing human prostate cancer cells.

Over-expression of bcl-2, a potent anti-apoptosis protein, is likely to be one of the genetic mechanisms through which human prostate cancer cells develop resistance to hormonal and other forms of therapy. To develop a therapeutic agent for hormone-resistant prostate cancer based on suppression of bcl-2 expression, we had previously designed and synthesized a dual-hammerhead ribozyme capable of recognizing and specifically cleaving human bcl-2 mRNA in vitro as well as in vivo. To increase the efficiency by which the anti-bcl-2 ribozyme can be delivered to target cells, we have created a recombinant replication-deficient (defective) adenoviral agent capable of expressing the anti-bcl-2 ribozyme upon infection. This viral agent effectively reduces intracellular levels of bcl-2 mRNA and protein in cultured LNCaP prostate cancer cells following standard infection procedures. Likewise, the defective adenovirus-anti-bcl-2 ribozyme induces extensive apoptosis in several androgen-sensitive (LNCaP) and androgen-insensitive (LNCaP/bcl-2 and PC-3) human prostate cancer cell lines that express differing amounts of bcl-2 protein. One androgen-insensitive prostate cancer cell line, DU-145, lacking in bcl-2 expression, was found to be completely refractory to the effects of the virus ribozyme, supporting the concept that the cytotoxic effects of the ribozyme are based solely on its effects on bcl-2 expression. Our results support further development of this adenovirus/anti-bcl-2 ribozyme for potential gene therapeutic purposes in certain forms of hormone-resistant prostate cancer where over-expression of bcl-2 proto-oncogene is indicated.

Adenoviruses, Human↗
PubMed1999

Fas antigen/CD-95 upregulation and activation during castration-induced regression of the rat ventral prostate gland.

BACKGROUND: Fas antigen/CD 95 is a 45-kDa transmembrane protein that can initiate intracellular signaling pathways, leading to apoptosis when it is clustered on the cell surface. A recent report claiming that the ventral prostate glands of lpr -/- mutant mice (lacking functional fas antigen) do not regress following castration prompted our analysis of the regressing rat ventral prostate gland for evidence that fas antigen might participate in the molecular process leading to prostate cell apoptosis after castration. METHODS: An RNase protection assay and Western blotting analysis were used to quantify fas antigen mRNA and protein expression in the regressing rat ventral prostate gland. Immunoprecipitates of fas antigen from membrane preparations made from control or castrated rat prostates were analyzed for coprecipitation of FADD and RIP proteins to assess the activation state of the fas antigen before and after castration. Finally, prostate tissues obtained from two different strains of lpr -/- mutant mice were analyzed for induced apoptosis after castration by the TUNEL staining method. RESULTS: Rat ventral prostate gland fas antigen mRNA and protein expression was upregulated approximately 3-5-fold in the 3-day castrated rat as compared to hormonally intact rats. Immunoprecipitates of fas antigen from membranes of ventral prostates from castrated rats contained significantly increased amounts of both FADD and RIP proteins when compared to those of intact or control operated rats. However, counts of TUNEL-labeled cells in the ventral prostate glands of castrated lpr -/- mice were not significantly different from those in castrated, genetically normal controls. Likewise, the morphology of apoptotic bodies formed in the prostates of castrated lpr -/- mice was indistinguishable from that in control animals. CONCLUSIONS: Fas antigen/CD-95, a protein that is involved in some forms of apoptosis, is upregulated during regression of the rat ventral prostate gland and becomes functionally "activated." However, our inability to distinguish any difference in the apoptosis rate or in the morphology of the apoptotic bodies formed in response to castration between lpr -/- mice and genetically normal controls indicates that, contrary to the prior report, functional fas protein is not required for castration-induced prostate cell apoptosis.

Animals↗