Objectives. Cellular senescence is a unique cellular response pathway thought to be closely assoc... more Objectives. Cellular senescence is a unique cellular response pathway thought to be closely associated with the aging process. The senescent phenotype is characterized by the loss of a cell’s ability to respond to proliferative and apoptotic stimuli even while normal metabolic activity and vitality is maintained. Recently, a novel biomarker, senescent-associated beta-galactosidase (SA-β-gal), was found to identify cells with the
The Columbia University experience of RT-PCR PSA as a predictive factor of stage and biochemical ... more The Columbia University experience of RT-PCR PSA as a predictive factor of stage and biochemical recurrence is reviewed by trying to explain its differences. 319 patients were included between January 1993 and March 1998. Radical prostatectomy was performed in all patients by the same surgeon. The RT-PCR protocol has been previously described (Katz et al., Urology, 1994). Biochemical recurrence was defined by a PSA greater than or equal to 0.2 ng/ml. Histological examination diagnosed 218 pT2 and 101 pT3 tumours. Thirty-four of the 218 pT2 patients (16%) had a positive RT-PCR versus 51 of the 101 pT3 patients (51%, p < 0.001). Analysis of Kaplan-Meier curves showed an 84% recurrence-free survival when RT-PER was negative versus 47% when RT-PCR was positive (Log-rank test, p = 0.0002). Multivariate analysis showed that independent predictive factors of biochemical recurrence were stage (p = 0.004), Gleason score estimated on the operative specimen (p = 0.010) and serum PSA (p = 0.047); RT-PCR (p = 0.075), strongly correlated with stage, was not an independent predictive factor. By exclusively comparing preoperative parameters, PSA (p = 0.004) and RT-PCR (p = 0.006) were found to be independent predictive factors compared to digital rectal examination (p = 0.371) and Gleason score on biopsies (p = 0.076). In this institution, RT-PCR PSA is a predictive parameter of stage and biochemical recurrence. No consensus has yet been reached in the literature concerning the reference protocol, as each team has developed its own RT-PCR technique applied to its own patient population. Comparison of results is therefore difficult.
Female sexual dysfunction is a common but poorly understood human condition. One of the aspects h... more Female sexual dysfunction is a common but poorly understood human condition. One of the aspects hindering progress in this area is the lack of appropriate animal models that can be used to study the complex factors involved in this sexual health problem. Recently, attention has focused on the probable role of vascular dynamics of the genital organs and their potential for impact on female sexuality. The objective of this study was to provide a better description of the vascular anatomy of the female rat vagina and external genital organs in an attempt to better develop this as an animal model to study female sexual dysfunction. Young female (nonestrous) virgin rats were anesthetized, the abdominal aorta was cannulated, and the distal vasculature was flushed and fixed in vivo for histological studies or for subsequent infusion with Mercox resin for vascular corrosion casting. Vascular corrosion casts of the external genitalia (vagina and vulva) were studied using a scanning electron microscope (SEM). Fixed tissue specimens were also embedded and sectioned for histochemical and immunohistochemical analysis. Scanning electron microscopy imaging allowed a description of the vascular and microvascular system of the nonestrous female rat genitalia. Major feeding vessels were located laterally in the muscular and serosal layers of the vagina with a complex system of interanastomosing collaterals between these large lateral trunks. The sub-epithelial region of the vaginal wall contains a dense and rich network of capillaries that perfuse the epithelium. These data were corroborated by two- dimensional histochemistry and immunostaining for endothelial and smooth muscle cells on paraffin-embedded thin sections of the female vagina and vulva. This study provides the first detailed three-dimensional en bloc view of the macro- and microvascular anatomy of the female rat vagina and vulva. The findings suggest an active interaction between the microvasculature and the epithelial cells of the vaginal wall. This study will provide the basic anatomic groundwork for future experiments on perturbations of the vascular system of the rat female genitalia in response to hormonal stimuli and various disease states.
Objectives. The androgen sensitivity of the mammalian penis has long been appreciated. However, t... more Objectives. The androgen sensitivity of the mammalian penis has long been appreciated. However, the precise biochemical and structural sequelae of alterations in testosterone, and the mechanisms thereof, remain to be elucidated. Recently, the androgen dependence of ...
To discuss challenges concerning treatment for chronic prostatitis/chronic pelvic pain syndrome (... more To discuss challenges concerning treatment for chronic prostatitis/chronic pelvic pain syndrome (CP/ CPPS) and review complementary and alternative medical (CAM) therapies being evaluated for this condition, we performed a comprehensive search of articles published from 1990–2005 using the
Bark extracts from the Amazonian rain forest tree Geissospermum vellosii (pao pereira), enriched ... more Bark extracts from the Amazonian rain forest tree Geissospermum vellosii (pao pereira), enriched in alpha-carboline alkaloids have significant anticancer activities in certain preclinical models. Because of the predominance of prostate cancer as a cause of cancer-related morbidity and mortality for men of Western countries, we preclinically tested the in vitro and in vivo effects of a pao pereira extract against a prototypical human prostate cancer cell line, LNCaP. When added to cultured LNCaP cells, pao pereira extract significantly suppressed cell growth in a dose-dependent fashion and induced apoptosis. Immunodeficient mice heterotopically xenografted with LNCaP cells were gavaged daily with pao pereira extract or vehicle control over 6 weeks. Tumor growth was suppressed by up to 80% in some groups compared with tumors in vehicle-treated mice. However, we observed a striking U-shaped dose-response curve in which the highest dose tested (50 mg/kg/d) was much less effective in ind...
The tropical shrub, Rauwolfia vomitoria, is a medicinal plant used traditionally to treat a varie... more The tropical shrub, Rauwolfia vomitoria, is a medicinal plant used traditionally to treat a variety of ailments. A bioactive beta-carboline alkaloid, alstonine, present in this extract was previously shown to have anti-cancer activity against cancer cell lines. This study considers the potential anti-prostate cancer activity of this extract in vitro and in vivo. Rauwolfia vomitoria extract standardized for beta-carboline alkaloids was tested for ability to influence the growth and survival of the human LNCaP prostate cancer cell line. A WST-1 assay was used to measure cell growth, and cell cycle analyses were conducted with flow cytometry. Western blot detection of PARP cleavage and accumulation of cells containing sub-genomic DNA indicated induction of apoptosis. Pathway specific microarray analyses were utilized to identify the effect of Rauwolfia extract on the expression of 225 genes. Mice xenografted with LNCaP cells were treated with the extract or placebo control, and tumor g...
Dietary studies of men throughout the world have identified certain foods/food-derived substances... more Dietary studies of men throughout the world have identified certain foods/food-derived substances that are correlated to prostate cancer risk. While radical modification of cultural dietary habits with the goal of preventing prostate cancer remains challenging, supplementation with certain foods and/or food-derived substances identified as having potential chemopreventative properties may be a feasible approach, particularly for Western cultures. Before such chemopreventative strategies can be recommended to patients, their benefits must be rigorously demonstrated in appropriately designed clinical trials. This paper discusses several agents currently under scientific scrutiny for prostate cancer chemopreventative activities and the data available, thus far.
... a Albany College of Pharmacy, 106 New Scotland Avenue, Albany, NY 12208-3492, USA. bStanford ... more ... a Albany College of Pharmacy, 106 New Scotland Avenue, Albany, NY 12208-3492, USA. bStanford University, Stanford, CA, USA. ... 8. RM Levin, N. Haugaard, L. O'Connor, R. Buttyan, AK Das, JS Dixon and JA Gosling , Obstructive response of human bladder to BPH vs. ...
Objectives. Cellular senescence is a unique cellular response pathway thought to be closely assoc... more Objectives. Cellular senescence is a unique cellular response pathway thought to be closely associated with the aging process. The senescent phenotype is characterized by the loss of a cell’s ability to respond to proliferative and apoptotic stimuli even while normal metabolic activity and vitality is maintained. Recently, a novel biomarker, senescent-associated beta-galactosidase (SA-β-gal), was found to identify cells with the
The Columbia University experience of RT-PCR PSA as a predictive factor of stage and biochemical ... more The Columbia University experience of RT-PCR PSA as a predictive factor of stage and biochemical recurrence is reviewed by trying to explain its differences. 319 patients were included between January 1993 and March 1998. Radical prostatectomy was performed in all patients by the same surgeon. The RT-PCR protocol has been previously described (Katz et al., Urology, 1994). Biochemical recurrence was defined by a PSA greater than or equal to 0.2 ng/ml. Histological examination diagnosed 218 pT2 and 101 pT3 tumours. Thirty-four of the 218 pT2 patients (16%) had a positive RT-PCR versus 51 of the 101 pT3 patients (51%, p < 0.001). Analysis of Kaplan-Meier curves showed an 84% recurrence-free survival when RT-PER was negative versus 47% when RT-PCR was positive (Log-rank test, p = 0.0002). Multivariate analysis showed that independent predictive factors of biochemical recurrence were stage (p = 0.004), Gleason score estimated on the operative specimen (p = 0.010) and serum PSA (p = 0.047); RT-PCR (p = 0.075), strongly correlated with stage, was not an independent predictive factor. By exclusively comparing preoperative parameters, PSA (p = 0.004) and RT-PCR (p = 0.006) were found to be independent predictive factors compared to digital rectal examination (p = 0.371) and Gleason score on biopsies (p = 0.076). In this institution, RT-PCR PSA is a predictive parameter of stage and biochemical recurrence. No consensus has yet been reached in the literature concerning the reference protocol, as each team has developed its own RT-PCR technique applied to its own patient population. Comparison of results is therefore difficult.
Female sexual dysfunction is a common but poorly understood human condition. One of the aspects h... more Female sexual dysfunction is a common but poorly understood human condition. One of the aspects hindering progress in this area is the lack of appropriate animal models that can be used to study the complex factors involved in this sexual health problem. Recently, attention has focused on the probable role of vascular dynamics of the genital organs and their potential for impact on female sexuality. The objective of this study was to provide a better description of the vascular anatomy of the female rat vagina and external genital organs in an attempt to better develop this as an animal model to study female sexual dysfunction. Young female (nonestrous) virgin rats were anesthetized, the abdominal aorta was cannulated, and the distal vasculature was flushed and fixed in vivo for histological studies or for subsequent infusion with Mercox resin for vascular corrosion casting. Vascular corrosion casts of the external genitalia (vagina and vulva) were studied using a scanning electron microscope (SEM). Fixed tissue specimens were also embedded and sectioned for histochemical and immunohistochemical analysis. Scanning electron microscopy imaging allowed a description of the vascular and microvascular system of the nonestrous female rat genitalia. Major feeding vessels were located laterally in the muscular and serosal layers of the vagina with a complex system of interanastomosing collaterals between these large lateral trunks. The sub-epithelial region of the vaginal wall contains a dense and rich network of capillaries that perfuse the epithelium. These data were corroborated by two- dimensional histochemistry and immunostaining for endothelial and smooth muscle cells on paraffin-embedded thin sections of the female vagina and vulva. This study provides the first detailed three-dimensional en bloc view of the macro- and microvascular anatomy of the female rat vagina and vulva. The findings suggest an active interaction between the microvasculature and the epithelial cells of the vaginal wall. This study will provide the basic anatomic groundwork for future experiments on perturbations of the vascular system of the rat female genitalia in response to hormonal stimuli and various disease states.
Objectives. The androgen sensitivity of the mammalian penis has long been appreciated. However, t... more Objectives. The androgen sensitivity of the mammalian penis has long been appreciated. However, the precise biochemical and structural sequelae of alterations in testosterone, and the mechanisms thereof, remain to be elucidated. Recently, the androgen dependence of ...
To discuss challenges concerning treatment for chronic prostatitis/chronic pelvic pain syndrome (... more To discuss challenges concerning treatment for chronic prostatitis/chronic pelvic pain syndrome (CP/ CPPS) and review complementary and alternative medical (CAM) therapies being evaluated for this condition, we performed a comprehensive search of articles published from 1990–2005 using the
Bark extracts from the Amazonian rain forest tree Geissospermum vellosii (pao pereira), enriched ... more Bark extracts from the Amazonian rain forest tree Geissospermum vellosii (pao pereira), enriched in alpha-carboline alkaloids have significant anticancer activities in certain preclinical models. Because of the predominance of prostate cancer as a cause of cancer-related morbidity and mortality for men of Western countries, we preclinically tested the in vitro and in vivo effects of a pao pereira extract against a prototypical human prostate cancer cell line, LNCaP. When added to cultured LNCaP cells, pao pereira extract significantly suppressed cell growth in a dose-dependent fashion and induced apoptosis. Immunodeficient mice heterotopically xenografted with LNCaP cells were gavaged daily with pao pereira extract or vehicle control over 6 weeks. Tumor growth was suppressed by up to 80% in some groups compared with tumors in vehicle-treated mice. However, we observed a striking U-shaped dose-response curve in which the highest dose tested (50 mg/kg/d) was much less effective in ind...
The tropical shrub, Rauwolfia vomitoria, is a medicinal plant used traditionally to treat a varie... more The tropical shrub, Rauwolfia vomitoria, is a medicinal plant used traditionally to treat a variety of ailments. A bioactive beta-carboline alkaloid, alstonine, present in this extract was previously shown to have anti-cancer activity against cancer cell lines. This study considers the potential anti-prostate cancer activity of this extract in vitro and in vivo. Rauwolfia vomitoria extract standardized for beta-carboline alkaloids was tested for ability to influence the growth and survival of the human LNCaP prostate cancer cell line. A WST-1 assay was used to measure cell growth, and cell cycle analyses were conducted with flow cytometry. Western blot detection of PARP cleavage and accumulation of cells containing sub-genomic DNA indicated induction of apoptosis. Pathway specific microarray analyses were utilized to identify the effect of Rauwolfia extract on the expression of 225 genes. Mice xenografted with LNCaP cells were treated with the extract or placebo control, and tumor g...
Dietary studies of men throughout the world have identified certain foods/food-derived substances... more Dietary studies of men throughout the world have identified certain foods/food-derived substances that are correlated to prostate cancer risk. While radical modification of cultural dietary habits with the goal of preventing prostate cancer remains challenging, supplementation with certain foods and/or food-derived substances identified as having potential chemopreventative properties may be a feasible approach, particularly for Western cultures. Before such chemopreventative strategies can be recommended to patients, their benefits must be rigorously demonstrated in appropriately designed clinical trials. This paper discusses several agents currently under scientific scrutiny for prostate cancer chemopreventative activities and the data available, thus far.
... a Albany College of Pharmacy, 106 New Scotland Avenue, Albany, NY 12208-3492, USA. bStanford ... more ... a Albany College of Pharmacy, 106 New Scotland Avenue, Albany, NY 12208-3492, USA. bStanford University, Stanford, CA, USA. ... 8. RM Levin, N. Haugaard, L. O'Connor, R. Buttyan, AK Das, JS Dixon and JA Gosling , Obstructive response of human bladder to BPH vs. ...
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