pRb2/p130 Decreases Sensitivity to Apoptosis Induced by Camptothecin and Doxorubicin but not by Taxol

Tonini, Tiziana; Gabellini, Chiara; Bagella, Luigi; D’Andrilli, Giuseppina; Masciullo, Valeria; Romano, Gaetano; Scambia, Giovanni; Zupi, Gabriella; Giordano, Antonio

doi:10.1158/1078-0432.ccr-04-0996

Cited by 12 publications

(8 citation statements)

References 38 publications

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“…44). Similar results were observed in ovarian cancer cells (CAOV-3), which were sensitized to camptothecin, a topoisomerase I inhibitor through RB phosphorylation (45). Although not a direct measure, induction of E2F activity in different tumor cell lines has been shown to correlate with increased sensitivity to etoposide (46).…”

Section: Discussionsupporting

confidence: 65%

Retinoblastoma Tumor Suppressor Status Is a Critical Determinant of Therapeutic Response in Prostate Cancer Cells

et al. 2007

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The retinoblastoma tumor suppressor protein (RB), a critical mediator of cell cycle progression, is functionally inactivated in the majority of human cancers, including prostatic adenocarcinoma. The importance of RB tumor suppressor function in this disease is evident because 25% to 50% of prostatic adenocarcinomas harbor aberrations in RB pathway. However, no previous studies challenged the consequence of RB inactivation on tumor cell proliferation or therapeutic response. Here, we show that RB depletion facilitates deregulation of specific E2F target genes, but does not confer a significant proliferative advantage in the presence of androgen. However, RB-deficient cells failed to elicit a cytostatic response (compared with RB proficient isogenic controls) when challenged with androgen ablation, AR antagonist, or combined androgen blockade. These data indicate that RB deficiency can facilitate bypass of first-line hormonal therapies used to treat prostate cancer. Given the established effect of RB on DNA damage checkpoints, these studies were then extended to determine the impact of RB depletion on the response to cytotoxic agents used to treat advanced disease. In this context, RB-deficient prostate cancer cells showed enhanced susceptibility to cell death induced by only a selected subset of cytotoxic agents (antimicrotubule agents and a topoisomerase inhibitor). Combined, these data indicate that RB depletion dramatically alters the cellular response to therapeutic intervention in prostate cancer cells and suggest that RB status could potentially be developed as a marker for effectively directing therapy. [Cancer Res 2007;67(13):6192-203]

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Section: Discussionsupporting

confidence: 65%

Retinoblastoma Tumor Suppressor Status Is a Critical Determinant of Therapeutic Response in Prostate Cancer Cells

et al. 2007

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“…These three drugs were chosen because they have different mechanisms for inducing apoptosis in cells. Both doxorubicin and camptothecin inhibit DNA and RNA synthesis; doxorubicin is a topoisomerase II inhibitor while camptothecin is a topoisomerase I inhibitor [6]. Thapsigargin is an endoplasmic reticulum (ER) stress inducer [7].…”

Section: Introductionmentioning

confidence: 99%

Effect of Apoptosis-Inducing Antitumor Agents on Endocardial Endothelial Cells

et al. 2011

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Chemotherapy is one of the common treatment modalities for cancer. Some of the antineoplastic drugs have, however, been found to be toxic for vascular endothelium, resulting in complications such as endothelial dysfunction, thromboembolism, heart failure, and cardiomyopathy. In this study, we investigated the cytotoxic effect of widely used antitumor agents doxorubicin, camptothecin, and thapsigargin on primary and immortalized porcine endocardial endothelial cells and compared with the effects of these agents on human umbilical vein endothelial cells, human aortic endothelial cells, and EA.hy926 cells. Our study revealed that endocardial endothelial cells are relatively resistant to apoptosis induced by these drugs. Interestingly, our study indicates that response to antitumor agents greatly differs depending on the site of origin of endothelial cells. Doxorubicin, camptothecin, and thapsigargin induce mitochondrial-dependent cell death following loss of mitochondrial membrane potential (MMP) in vascular endothelial cells, with subsequent increase in sub-G0 population. In endocardial endothelial cells, there was no MMP loss; and only cell cycle arrest either at G1 or S phases was observed when the cells were treated with doxorubicin, camptothecin, and thapsigargin.

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“…Accumulating evidence shows that the manipulation of the cell cycle may either prevent or induce an apoptotic response [Pucci et al, 2000. This ability has been recognized for several cell cycle proteins such as p53 and the retinoblastoma family members, pRb/p105, p107, and pRb2/p130 [Morgenbesser et al, 1994; Paggi et al, 1996; Pucci et al, 2002; Tonini et al, 2004. Data concerning the role of cyclin‐dependent kinases (CDKs), cyclins, and CDK inhibitors (CKIs) also support a direct coupling between the proliferating machinery and the apoptotic process [Kasten and Giordano, 1998.…”

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confidence: 99%

The myths of motivation: Time for a fresh look at some received wisdom in the eating disorders?

Waller

2011

Intl J Eating Disorders

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The eating disorders typically involve poor motivation to change. This article reviews the evidence behind many of our beliefs about motivation and whether we need a different conceptual framework for understanding why patients commonly get "stuck." The outcome literature is reviewed, and demonstrates that there is little evidence that we are effective in enhancing motivation to induce changes in symptoms. Indeed, there are suggestions that commonly used models are unhelpful. Verbal expressions of motivation are not the best indicator of likely treatment response, and can best be understood as providing a "manifesto," which has functions that can obstruct recovery from the eating disorder. A behavioral analysis of motivation is likely to be more effective. Cognitive, emotional, and behavioral methods for enhancing motivation are outlined, with the aim of bypassing the motivational manifesto and encouraging positive therapeutic change.

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pRb2/p130 Decreases Sensitivity to Apoptosis Induced by Camptothecin and Doxorubicin but not by Taxol

Cited by 12 publications

References 38 publications

Retinoblastoma Tumor Suppressor Status Is a Critical Determinant of Therapeutic Response in Prostate Cancer Cells

Retinoblastoma Tumor Suppressor Status Is a Critical Determinant of Therapeutic Response in Prostate Cancer Cells

Effect of Apoptosis-Inducing Antitumor Agents on Endocardial Endothelial Cells

The myths of motivation: Time for a fresh look at some received wisdom in the eating disorders?

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