The relation of androgen receptors status, neuroendocrine differentiation and angiogenesis to biochemical failure after radical prostatectomy for localized prostate cancer

Revelos, Kyriakos; Petraki, Constantina; Vaslamatzis, Michael; Papanastassiou, P.; Mastoris, C.; Argyrakos, Theodoros; Alevizopoulos, Nektarios; Vrionis, E.; Koutsilieris, M.

doi:10.1200/jco.2004.22.14_suppl.4691

Cited by 18 publications

(24 citation statements)

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“…This is in accordance with two other studies [25,28] that also reported a higher MVD in HR prostate cancer than HN tumours. We also found that MVD correlated with the Gleason score of the tumours, which is supported by several studies [2,3,25,28]. There was no apparent significant difference in the number of blood vessels between benign areas and early HN prostate tumours, probably because the HN tumours analysed in the present study were at a very early tumour stage of T1b.…”

Section: Discussionsupporting

confidence: 91%

ADAMTS1, a putative anti‐angiogenic factor, is decreased in human prostate cancer

Gustavsson¹,

Wang²,

Jennbacken³

et al. 2009

BJU International

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quantified by counting the number of CD34-positive blood vessels. RESULTSADAMTS1 was strongly expressed in the luminal epithelial cells in benign prostate glands, whereas expression was significantly lower in prostate cancer cells. There was no obvious difference between hormone-naïve and hormone-refractory tumours, and ADAMTS1 expression did not correlate with Gleason score. However, in hormonerefractory tumours from patients with metastatic disease, the expression of ADAMTS1 was significantly lower than in tumours from patients without metastases. Furthermore, the MVD was higher in hormone-refractory than in hormone-naïve tumours and benign tissue, and MVD correlated with Gleason score. There was no association between ADAMTS1 and MVD in the hormone-naïve tumours, while hormone-refractory tumours with low ADAMTS1 expression had a higher MVD than those with moderate/high expression. CONCLUSIONADAMTS1 expression is decreased in prostate cancer, and might be involved in the early steps of prostate cancer development. Further, ADAMTS1 might have an antiangiogenic and antimetastatic role in hormone-refractory prostate cancer, where low ADAMTS1 expression is associated with a high MVD and metastasis. KEYWORDSADAMST1, angiogenesis, androgen independent, microvessel density, prostate cancer OBJECTIVETo investigate the expression of 'ADAM metallopeptidase with thrombospondin type

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Section: Discussionsupporting

confidence: 91%

ADAMTS1, a putative anti‐angiogenic factor, is decreased in human prostate cancer

Gustavsson¹,

Wang²,

Jennbacken³

et al. 2009

BJU International

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“…The data for MVD were unavailable for the RP cohort. Several conflicting reports exist regarding the prognostic power of VEGF and MVD for PC (Green et al , 2007; Revelos et al , 2007; Mucci et al , 2009; Boxler et al , 2010), and it is possible that other markers of angiogenesis can improve PC risk stratification beyond the findings in this study.…”

Section: Discussionmentioning

confidence: 71%

Prognostic significance of aberrantly silenced ANPEP expression in prostate cancer

et al. 2013

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Background:Novel biomarkers for prostate cancer (PC) are urgently needed. This study investigates the expression, epigenetic regulation, and prognostic potential of ANPEP in PC.Methods:Aminopeptidase N (APN; encoded by ANPEP) expression was analysed by immunohistochemistry using tissue microarrays representing 267 radical prostatectomy (RP) and 111 conservatively treated (CT) PC patients. Clinical end points were recurrence-free survival (RFS) and cancer-specific survival (CSS), respectively. The ANPEP promoter methylation levels were determined by bisulphite sequencing or MethyLight analysis in 278 nonmalignant and PC tissue samples, and in cell lines.Results:The APN expression was significantly downregulated in PC compared with nonmalignant prostate tissue samples. Aberrant promoter hypermethylation was frequently observed in PC tissue samples, and 5-aza-2′-deoxycytidine induced ANPEP expression in three hypermethylated prostate cell lines, suggesting epigenetic silencing. Negative APN immunoreactivity was significantly associated with short RFS and short CSS in the RP and CT cohort, respectively, independently of routine clinicopathological predictors. Combining APN with a known angiogenesis marker (vascular endothelial growth factor or microvessel density) improved risk prediction significantly in both cohorts.Conclusion:Our results suggest negative APN immunoreactivity as a new independent adverse prognostic factor for patients with clinically localised PC and, furthermore, that epigenetic mechanisms are involved in silencing of ANPEP in PC.

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“…One of the major failures in successfully treating CaP is due to the presence of a mixture of CaP cells [comprising androgen-dependent and androgen-independent cells] as lesions of different androgen-status respond differently to the chemotherapy [10. We investigated the effect of Lupeol (10–50 μM) treatment on the viability of androgen-sensitive (LNCaP, CWR22Rν1), androgen-insensitive (PC-3 and DU145) CaP cells and normal prostate epithelial cell (PrEC).…”

Section: Resultsmentioning

confidence: 99%

“…These data is significant because Lupeol caused inhibition in the growth of human CaP cells irrespective of their androgen responsive status and spares normal prostate epithelial cells. In addition, there is an increasing interest and emphasis given by scientists and clinicians on natural diet-based agents which are capable of selective/preferential elimination of cancer cells without affecting normal cells [10]. …”

Section: Resultsmentioning

confidence: 99%

Lupeol triterpene, a novel diet-based microtubule targeting agent: Disrupts survivin/cFLIP activation in prostate cancer cells

Saleem¹,

Murtaza²,

Witkowsky³

et al. 2009

Biochemical and Biophysical Research Communications

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Recently we showed Lupeol, a triterpene, found in fruits and vegetables inhibits the growth of tumors originated from human androgen-sensitive prostate cancer (CaP) cells and decreases the serum-PSA levels in a mouse model. Here, we provide evidence that Lupeol inhibits the growth of androgensensitive as well as androgen-insensitive CaP cells by inducing G2/M cell cycle arrest without exhibiting any toxicity to normal human prostate epithelial cells (PrEC) at the doses at which it kills cancer cells. We observed that Lupeol treatment to LNCaP and DU145 cells resulted in a dose dependent (i) decrease in the protein levels of Cyclins-A, -B1, -D1, -D2, -E2, cyclin-dependent kinase (cdk)-2 and (ii) increase in the protein level of CDK-inhibitor p21. Since G2/M cell cycle phase is regulated by microtubule assembly, we investigated effect of Lupeol on microtubule assembly, its regulation and down-stream targets in CaP cells. Lupeol treatment significantly modulated the level of (i) microtubule components α-tubulin and β-tubulin, (ii) microtubule-regulatory protein stathmin, and (iii) microtubule-regulatory downstream target/pro-survival protein survivin. Lupeol treatment also decreased the level of anti-apoptotic protein cFLIP. Finally, Lupeol was observed to significantly decrease the transcriptional activation of Survivin and cFLIP genes in CaP cells. We conclude that the Lupeol-induced growth inhibition of CaP cells is a net outcome of simultaneous effects on Stathmin, cFLIP, and Survivin which results in the disruption of microtubule assembly. We suggest that Lupeol alone or as an adjuvant to other microtubule agents could be developed as a potential agent for the treatment of human CaP.

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The relation of androgen receptors status, neuroendocrine differentiation and angiogenesis to biochemical failure after radical prostatectomy for localized prostate cancer

Cited by 18 publications

References 0 publications

ADAMTS1, a putative anti‐angiogenic factor, is decreased in human prostate cancer

ADAMTS1, a putative anti‐angiogenic factor, is decreased in human prostate cancer

Prognostic significance of aberrantly silenced ANPEP expression in prostate cancer

Lupeol triterpene, a novel diet-based microtubule targeting agent: Disrupts survivin/cFLIP activation in prostate cancer cells

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