Molecular markers of outcome after radiotherapy in patients with prostate carcinoma

Pollack, Alan; Cowen, D.; Troncoso, Patricia; Zagars, Gunar K.; Eschenbach, Andrew C. von; Meistrich, Marvin L.; McDonnell, Timothy J.

doi:10.1002/cncr.11230

Cited by 96 publications

(72 citation statements)

References 46 publications

(77 reference statements)

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“…Clinical studies have shown that bcl-2 overexpression, and/or abnormal bax expression, is associated with an increased risk of biochemical failure after radiotherapy (12,13,23). Moreover, Bcl-2 is overexpressed in recurrent tumors after RT (24,25).…”

Section: Discussionmentioning

confidence: 99%

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Antisense Bcl-2 sensitizes prostate cancer cells to radiation

Hachem

Pollack

2005

Prostate

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BACKGROUND-Bcl-2 is anti-apoptotic and overexpression is associated with prostate tumor aggressiveness. We hypothesized that Bcl-2 has a role in prostate cancer radiation (RT) response. The relationship of Bcl-2 expression in four prostate cancer cell lines, and the effect of modulating expression with a Bcl-2 antisense oligonucleotide (G3139, Genasense ® , oblimersen sodium, Genta Incorporated), to RT was examined.

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Section: Discussionmentioning

confidence: 99%

“…In prostate cancer, overexpression of bcl-2 is associated with prostate tumor aggressiveness (7)(8)(9). Moreover, Bcl-2 protein is increased in the majority of tumors from men with androgen-refractory disease and is associated with resistance to androgen deprivation and RT (4,6,(10)(11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

Antisense Bcl-2 sensitizes prostate cancer cells to radiation

Hachem

Pollack

2005

Prostate

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“…Abnormal bax expression in our study was classified as overexpression or underexpression based on the results of a prior report (7). The initial rationale for this subdivision was that bax overexpression would be favorable in the setting of radiation due to the promotion of apoptosis, while its underexpression should lead to less of a response to radiation.…”

Section: Discussionmentioning

confidence: 99%

Bcl-2 and bax expression and prostate cancer outcome in men treated with radiotherapy in Radiation Therapy Oncology Group protocol 86-10

Khor

DeSilvio

et al. 2006

International Journal of Radiation Oncology*Biology*Physics

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Purpose-Bcl-2 and bax are proteins with opposing roles in apoptosis regulation; yet abnormal expression of either has been associated with failure after radiotherapy (RT). In this study we examined bcl-2 and bax expression as predictive markers in men treated with radiotherapy ± androgen deprivation on Radiation Therapy Oncology Group (RTOG) protocol 86-10.Experimental Design-Suitable archival diagnostic tissue was obtained from 119 (26%) patients for bcl-2 analysis and 104 (23%) patients for bax analysis. Cox proportional hazards multivariate analysis was used to determine the relationship of abnormal bcl-2 and bax expression to the end points of local failure, distant metastasis, cause-specific mortality, and overall mortality. Bcl-2 overexpression was classified as any tumor cell cytoplasmic staining and altered bax expression was classified as greater or lesser cytoplasmic staining intensity of tumor cells as compared with adjacent normal prostate epithelium.Results-The study cohort exhibited bcl-2 overexpression in 26% (n = 30) of cases and abnormal bax expression in 47% (n = 49) of cases. A borderline significant relationship was observed between abnormal bax expression and higher Gleason score (p = 0.08). In univariate and multivariate analyses, there was no statistically significant relationship seen between abnormal bcl-2 or bax expression and outcome. Conclusions-Abnormal bcl-2 and bax expression were not related to any of the end points tested. The cohort examined was comprised of patients with locally advanced disease and it is possible that these markers may be of greater value in men with earlier-stage prostate cancer.

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“…Many studies have established that bcl-2 can protect against cell death resulting from genotoxic stress in general and p53 activation specifically Adams and Cory, 1998;Schumacher et al, 2001). Additionally, recent findings suggest that bcl-2 levels in tumor cells may provide important predictive information in cancer patients (Mano et al, 1999;Pollack et al, 2003). Understanding the clinically relevant molecular variables that are likely to influence p53 function, including upregulation of the anti-apoptotic bcl-2 oncoprotein, will facilitate the ultimate success of these trials.…”

Section: Discussionmentioning

confidence: 99%