Malignant changes in the prostate with ageing

Dunsmuir,; Hrouda,; Kirby,

doi:10.1046/j.1464-410x.1998.0820s1047.x

Cited by 17 publications

(13 citation statements)

References 112 publications

(108 reference statements)

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“…Preneoplastic prostate lesions such as HGPIN are commonly observed in asymptomatic men during the fourth and fifth decade of life, and it is believed that such precursors require 2 to 3 decades to develop into clinically relevant prostate cancers (70). We found that feeding celecoxib to TRAMP mice significantly delayed the development of prostate cancer, and effectively eliminated the occurrence of metastasis in these animals.…”

Section: Discussionmentioning

confidence: 75%

“…The high incidence of prostate cancer in older men suggests that agents that inhibit or delay disease development might significantly reduce cancer morbidity and mortality (70). Preneoplastic prostate lesions such as HGPIN are commonly observed in asymptomatic men during the fourth and fifth decade of life, and it is believed that such precursors require 2 to 3 decades to develop into clinically relevant prostate cancers (70).…”

Section: Discussionmentioning

confidence: 99%

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Suppression of Prostate Carcinogenesis by Dietary Supplementation of Celecoxib in Transgenic Adenocarcinoma of the Mouse Prostate Model

Gupta¹,

et al. 2004

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Celecoxib feeding resulted in a significant decrease in prostate (56%; P < 0.0003) and genitourinary weight (48%; P < 0.008). Sequential magnetic resonance imaging analysis of celecoxib-fed mice documented lower prostate volume compared with the AIN 76A-fed group. Histopathological examination of celecoxib-fed animals showed reduced proliferation, and down-modulation of COX-2 and prostaglandin E 2 levels in the dorsolateral prostate and plasma, respectively. These results correlated with retention of antimetastasis markers, viz E-cadherin, and ␣-and ␤-catenin, along with a significant decrease in vascular endothelial growth factor protein expression. Celecoxib supplementation also resulted in enhanced in vivo apoptosis in the prostate as monitored by several techniques including a recently perfected technique of 99m Tc-labeled annexin V in live animals followed by phosphor imaging. One striking observation in an additional study was that celecoxib feeding to mice with established tumors (16 weeks of age) significantly improved their overall survival (P ‫؍‬ 0.014), compared with AIN 76A-fed group. Our findings suggest that celecoxib may be useful in chemoprevention of prostate cancer.

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Section: Discussionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Suppression of Prostate Carcinogenesis by Dietary Supplementation of Celecoxib in Transgenic Adenocarcinoma of the Mouse Prostate Model

Gupta¹,

et al. 2004

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“…1 Growth of PECs is not stimulated by androgens in vitro 1 although anti-androgen intervention inhibits the growth of adenocarcinomas in vivo. 13 Identification of such factors and their incorporation into culture medium could generate a more robust in vitro model.…”

Section: Discussionmentioning

confidence: 99%

“…11 Inheritance of susceptibility genes does not appear to account for more than a small proportion of cases. 12 Ageing is the most significant risk factor identified to date 13 and, although the World Health Organization lists meat and animal fat intake as other risk factors, 14 the aetiology of CaP is still poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Primary cultures of prostate cells and their ability to activate carcinogens

Martin

Cole

Muir

et al. 2002

Prostate Cancer Prostatic Dis

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Differences in the incidence of prostate cancer (CaP) amongst different migrant populations point to causative agents of dietary and/or environmental origin. Prostate tissues were obtained following transurethral resection of the prostate (TURP) or radical retropubic prostatectomy. After surgery, TURP-derived or tumour-adjacent tissue fragments were minced in warm PFMR-4A medium (37 C) and suspensions pipetted into collagen-coated petri dishes. Non-adherent material was removed by washing with fresh medium after 12 h. Adhered cells subsequently reacted positively with monoclonal antibodies to prostate specific antigen (PSA). PSA was also detected in the medium. The genotoxicities of the chemical carcinogens 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP), its N-hydroxy metabolite (N-OH-PhIP) and benzo[a]pyrene (B[a]P) in adherent cell populations from different donors (n ¼ 8) were examined. Cells were treated in suspension for 30 min at 37 C in the presence of the DNA repair inhibitors hydroxyurea (HU) and cytosine arabinoside (ara-C). DNA single-strand breaks were detected in cells by the alkaline single cell-gel electrophoresis ('Comet') assay and quantified by measuring comet tail length (CTL) in mm. All three carcinogens induced dose-related increases in CTLs (P < 0.0001) in cells from four donors 24 h post-seeding. However, in cells from a further two donors the genotoxic effects of PhIP, N-OH-PhIP and B[a]P were much less apparent after 48 h than after 24 h in culture. After 96 h in culture, cells from these donors appeared to be resistant to the comet-forming activity of the compounds. However, B[a]P-DNA adducts were still measurable by 32 P-postlabelling for up to 14 days following a 24-h exposure to 50 mM B[a]P in adhered cells from another two donors. This study shows that primary cultures of cells derived from the prostate can activate members of two classes of chemical carcinogens. Further development may provide a robust model system in which to investigate the aetiology of CaP.

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“…4 and references therein). Such preneoplastic lesions have been found in young men in their 20s and are common in men in their 50s (5). However, clinically detectable prostate cancer does not generally manifest itself until the 60s.…”

mentioning

confidence: 99%

Akt/cAMP-Responsive Element Binding Protein/Cyclin D1 Network: A Novel Target for Prostate Cancer Inhibition in Transgenic Adenocarcinoma of Mouse Prostate Model Mediated by Nexrutine, a Phellodendron Amurense Bark Extract

Kumar¹,

Bhaskaran²,

Ganapathy³

et al. 2007

Clinical Cancer Research

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Purpose: Development of prostate cancer prevention strategies is an important priority to overcome high incidence, morbidity, and mortality. Recently, we showed that Nexrutine, an herbal extract, inhibits prostate cancer cell proliferation through modulation of Akt and cAMP-responsive element binding protein (CREB)^mediated signaling pathways. However, it is unknown if Nexrutine can be developed as a dietary supplement for the prevention of prostate cancer. In this study, we used the transgenic adenocarcinoma of mouse prostate (TRAMP) model to examine the ability of Nexrutine to protectTRAMP mice from developing prostate cancer. Experimental Design: Eight-week-oldTRAMP mice were fed with pelleted diet containing 300 and 600 mg/kg Nexrutine for 20 weeks. Efficacy of Nexrutine was evaluated by magnetic resonance imaging at 18 and 28 weeks of progression and histologic analysis of prostate tumor or tissue at the termination of the experiment. Tumor tissue was analyzed for modulation of various signaling molecules. Results: We show that Nexrutine significantly suppressed palpable tumors and progression of cancer in the TRAMP model. Expression of total and phosphorylated Akt, CREB, and cyclin D1 was significantly reduced in prostate tissue from Nexrutine intervention group compared with tumors from control animals. Nexrutine also inhibited cyclin D1 transcriptional activity in androgen-independent PC-3 cells. Overexpression of kinase dead Akt mutant or phosphorylationdefective CREB inhibited cyclin D1transcriptional activity. Conclusions: The current study shows that Nexrutine-mediated targeting of Akt/CREBî nduced activation of cyclin D1prevents the progression of prostate cancer. Expression of CREB and phosphorylated CREB increased in human prostate tumors compared with normal tissue, suggesting their potential use as prognostic markers.Prostate cancer is the second leading cause of cancer-related deaths in men and expected to lead to f27,350 deaths in 2006 (1). African American men have the highest incidence of prostate cancer in the world, whereas Asian men native to their countries who consume a low-fat, high-fiber diet have the lowest risk (2). Epidemiologic studies suggest that a reduced risk of cancer is associated with the consumption of a phytochemical-rich diet that includes fruits and vegetables (3). Evidence suggests that prostate cancer progresses from normal epithelium to proliferative inflammatory atrophy, to low-grade prostatic intraepithelial neoplasia (PIN), and to high-grade PIN that eventually progresses to the more aggressive-metastatic and clinically evident prostate cancer (ref. 4 and references therein). Such preneoplastic lesions have been found in young men in their 20s and are common in men in their 50s (5). However, clinically detectable prostate cancer does not generally manifest itself until the 60s. In addition, the occurrence of precancerous lesions is more prevalent (about 1 in three men) than the incidence of carcinoma (about one in nine men; ref. 6). Therefore, the develop...

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Malignant changes in the prostate with ageing

Cited by 17 publications

References 112 publications

Suppression of Prostate Carcinogenesis by Dietary Supplementation of Celecoxib in Transgenic Adenocarcinoma of the Mouse Prostate Model

Suppression of Prostate Carcinogenesis by Dietary Supplementation of Celecoxib in Transgenic Adenocarcinoma of the Mouse Prostate Model

Primary cultures of prostate cells and their ability to activate carcinogens

Akt/cAMP-Responsive Element Binding Protein/Cyclin D1 Network: A Novel Target for Prostate Cancer Inhibition in Transgenic Adenocarcinoma of Mouse Prostate Model Mediated by Nexrutine, a Phellodendron Amurense Bark Extract

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