Statin use is associated with improved biochemical outcome after high-dose radiotherapy for clinically localized prostate cancer

Katz, Michael E.; Zeléfsky, Michael J.; Marion, C; Yamada, Yoshiya; Kattan, Michael W.; Leibel, Steven A.

doi:10.1016/s0360-3016(03)01114-3

Cited by 18 publications

(5 citation statements)

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“…Our findings demonstrate that cholesterol-lowing trials could be more effective in suppression of prostate cancer growth than expected. These facts provide significant molecular evidences to support the previous studies that cholesterol-lowing trials, such as drugs, diet and life style, are correlated with aggressiveness of prostate cancer [2,3,[30][31][32].…”

Section: Discussionsupporting

confidence: 80%

Cholesterol level of lipid raft microdomains regulates apoptotic cell death in prostate cancer cells through EGFR‐mediated Akt and ERK signal transduction

Lee

Yoon

et al. 2007

The Prostate

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Section: Discussionsupporting

confidence: 80%

Cholesterol level of lipid raft microdomains regulates apoptotic cell death in prostate cancer cells through EGFR‐mediated Akt and ERK signal transduction

Lee

Yoon

et al. 2007

The Prostate

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“…A total of 3229 publications were identified during the initial search (see Additional file 1. ), and after employing exclusion criteria, a total of 22 studies were included for PCa recurrence analysis 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 ( Table 1 ), 8 trials were available for PCa-specific mortality 22 30 31 32 33 34 35 36 ( Table 2 ), and 13 for BCR-free survival analysis 8 9 11 14 17 20 25 29 36 37 38 39 40 ( Table 3 ). Among 22 studies included in meta-analysis for PCa recurrence, 14 included a population primarily treated with radical prostatectomy (RP).…”

Section: Resultsmentioning

confidence: 99%

“…One of 13 trials evaluating the BCR-free survival suggested that statins users had a lower 5-year BCR-free survival rate compared with non-users 17 , while some reveled reversely 9 25 37 or showed there was no difference between two groups 20 . Meanwhile, the BCR-free survival rate at 8 or 9-year were still inconsistent 8 14 40 .…”

Section: Discussionmentioning

confidence: 99%

The effect of statins on prostate cancer recurrence and mortality after definitive therapy: a systematic review and meta-analysis

Tan

Wei

Yang

et al. 2016

Sci Rep

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In this work, we aim to further analyze the association of statins use with biochemical recurrence (BCR) of prostate cancer (PCa) and PCa-specific mortality after definitive therapy. A systematic literature search of PubMed, MEDLINE, and EMBASE through Jul 2015 was conducted. Pooled Hazard ratio (HR) estimates with corresponding 95% confidence intervals (CIs) were calculated using random-effects model. STATA version 10 (Stata corporation, college station, TX) was employed to conduct all statistical analyses. A total of 22 and 8 studies contributed to the biochemical recurrence analysis and PCa-specific mortality, respectively. 13 trials were included for BCR-free survival analysis. The combined result showed statins users had lowered 12% BCR risk of PCa compared with non-users (HR = 0.88, 95%CI: 0.765–0.998) (p < 0.05). The association was null among the men who underwent radical prostatectomy as primary therapy (HR = 0.96, 95%CI: 0.83–1.09), while the improved outcomes had be seen among patients who received radiation therapy (HR = 0.67, 95%CI: 0.48–0.86). After excluding the patients undergoing ADT, participants did not benefit from statins use (HR = 0.94, 95%CI: 0.77–1.11). Meanwhile, long-term statins using did not alter recurrence risk. A lower risk of prostate cancer-specific mortality was observed among statins users (HR = 0.68, 95%CI: 0.56–0.80). There was a plausible trend towards increasing the BCR-free survival rate among statins users.

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“…In summary, the data presented in this study suggested that inhibiting endothelial dysfunction with statins may limit the initiation and the progression of radiation atherosclerosis, fibrosis and thrombosis. Statins have also been described to have anticancer activity by acting as radiosensitizers (53,54). Therefore, statins may be proposed as a therapeutic strategy not only to improve radiotherapy but also for reducing the risk of radiation pathologies.…”

Section: Discussionmentioning

confidence: 99%

Pravastatin Limits Endothelial Activation after Irradiation and Decreases the Resulting Inflammatory and Thrombotic Responses

et al. 2005

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Endothelial dysfunction has been implicated in the pathogenesis of atherosclerosis, fibrosis and vascular occlusion after radiation therapy. Statins have been reported to improve endothelial function; however, this beneficial effect on endothelial cells has never been investigated after irradiation. Therefore, using human microvascular endothelial cells from lung that had been irradiated with 5 or 10 Gy, we assessed the effect of pravastatin on endothelial activation by ELISA, cell-ELISA and electrophoretic mobility shift assay and increased blood-endothelial cell interactions by a flow adhesion assay. Pravastatin inhibited the overproduction of monocyte chemoattractant protein 1, IL6 and IL8 and the enhanced expression of intercellular adhesion molecule 1 but had no effect on platelet-endothelial cell adhesion molecule 1 expression. Moreover, pravastatin down-regulated the radiation-induced activation of the transcription factor activator protein 1 but not of nuclear factor-kappaB. Finally, an inhibition by pravastatin of increased adhesion of leukocytes and platelets to irradiated endothelial cells was observed. The effect of pravastatin was maintained up to 14 days after irradiation and was reversed by mevalonate. Pravastatin exerts persistent anti-inflammatory and anti-thrombotic effects on irradiated endothelial cells. Statins may be considered in therapeutic strategies for the management of patients treated with radiation therapy.

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Statin use is associated with improved biochemical outcome after high-dose radiotherapy for clinically localized prostate cancer

Cited by 18 publications

References 0 publications

Cholesterol level of lipid raft microdomains regulates apoptotic cell death in prostate cancer cells through EGFR‐mediated Akt and ERK signal transduction

Cholesterol level of lipid raft microdomains regulates apoptotic cell death in prostate cancer cells through EGFR‐mediated Akt and ERK signal transduction

The effect of statins on prostate cancer recurrence and mortality after definitive therapy: a systematic review and meta-analysis

Pravastatin Limits Endothelial Activation after Irradiation and Decreases the Resulting Inflammatory and Thrombotic Responses

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