CLEMENT C IP

..Methylseleninic acid could be an excellent tool, especially for molecular mechanism studies in cell culture, and some of these attributes are discussed...

..Based on this information, a number of signaling pathways are proposed that could potentially provide insight into how selenium might block cell cycle progression and induce cell death...

..These observations suggest that the responsiveness of mammary epithelial cells to CLA intervention may be dependent on their proliferative status...

..This is achieved by simultaneously modulating certain molecular pathways that are responsible for inhibiting cell proliferation and enhancing apoptosis...

..Thus selenium chemoprevention efficacy can be separated experimentally from selenoprotein synthesis using this model system...

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..These confounding changes of the other unsaturated fatty acids in contributing to the effect of 10,12-CLA need to be clarified...

..These findings suggest that selenium (MSC) can serve as a therapeutic agent aimed at disruption of AR signaling for prostate cancer...

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..These two pathways may act in a cooperative manner to switch on the full force of the apoptotic machinery when cells are treated with both VES and MSA...

..Signaling between androgen receptor (AR) and mTOR may be crucial for prostate cancer cells to endure the low androgen and suboptimal nutrient conditions produced by androgen deprivation therapy...

..In summary, our data demonstrate that apoptosis induced by t10,c12-CLA is mediated, at least in part, through an atypical ER stress response that culminates in the induction of CHOP and the cleavage of caspase-12...

..Based on our findings, we propose a working model to capture the salient features of the apoptotic signaling circuitry of alpha-TOS...

..Mitochondrial activation of caspase-9 is in part responsible for the synergy. The present study aimed at examining the death receptor pathway in activating caspase-8 by the two-drug combination...

..The present study thus provides strong evidence to support an important role of ER stress response in mediating the anticancer effect of selenium...

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..The above findings led us to believe that Prx1 may be a therapeutic target in blocking the transition of prostate cancer from an androgen-dependent to an androgen-refractory phenotype...

..The functional significance of Bim was confirmed by the observation that RNA interference of Bim markedly reduced the potency of selenium/doxorubicin to induce apoptosis...

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..Both the intrinsic and extrinsic apoptotic pathways were involved in the sensitization mechanism. Our study supports the idea that marshalling ER stress apoptotic response is conducive to chemotherapeutic sensitization...

..The present study was designed to investigate whether a combination of alphaTS and MSA would produce an additive or a greater than additive effect in suppressing AR level, AR transactivation, and prostate-specific antigen (PSA)...

..Based on the above information, we suggest that disrupting the interaction between Prx1 and AR may serve as a fruitful new target in the management of prostate cancer...

..Our finding that MSA reduces androgen receptor availability by blocking androgen receptor transcription provides justification for a mechanism-driven intervention strategy in using selenium to control prostate cancer progression...

..The future design of new anticancer tocopherol analogs should incorporate the ether linkage of the side chain for esterase resistance as well as other structural modifications for enhanced blocking of membrane signaling...

..40; 95% confidence interval, 0.16-1.01). Our findings suggest that, although CLA intake was not related to overall breast cancer risk, there may be associations with tumor biology at least among premenopausal women...

..Moreover, we propose that each CLA isomer uniquely modifies the mammary stromal "soil" in a manner that is useful for chemoprevention of breast cancer...

..Together, the data suggest that CLA may be an excellent candidate for prevention of breast cancer...

..Both cis-9, trans-11 and trans-10, cis-12 CLA isomers were effective in inhibiting angiogenesis in vitro in a dose-dependent fashion. The ability of CLA to inhibit angiogenesis may contribute to its efficacy as a chemopreventive agent...

..However, even though c9,t11-CLA was not efficacious in the erbB2 model, its ability to inhibit mammary tumor development in rat models suggests that it may have activity for prevention of some types of breast cancer...

..The above information suggests that the Nrf2-Prx1 axis may be a fruitful target for intervention with respect to inhibiting the malignant progression and/or reducing the treatment resistance of cancer cells...

..The present study demonstrates the utility of a genome-wide analysis to elucidate the mechanism of selenium chemoprevention...

..Thus, the selection of selenium biomarkers for evaluation in an intervention trial must be based on empirical data derived from the cancer cell type of interest...

..Thus, differential regulation of ERalpha and ERbeta in breast cancer cells may represent a novel mechanism of selenium action and provide a rationale for selenium breast cancer prevention trial...

..The AR-stimulatory effect of an unstable tissue oxygenation milieu of a tumor is likely to contribute to treatment resistance and the emergence of recurrent prostate cancer...

..The finding suggests that selenium-mediated dephosphorylation of Akt via calcineurin is likely to be an additional mechanism in regulating the status of phospho-Akt...

..These findings are consistent with the hypothesis that human Prx1 and Prx2 possess unique functions and regulatory mechanisms and that Cys(83) bestows a distinctive identity to Prx1...

..Our study provides new insight into the antiapoptotic function of Prx1 in modulating radiosensitivity and provides the impetus to monitor the influence of Prx1 levels in the management of lung cancer...

..These results demonstrate that t10,c12-CLA triggers apoptosis of p53 mutant murine mammary tumor cells through the mitochondrial pathway by targeting Bcl-2...

..Our study proved that proteomics analysis employing the BIAM-labeling method can provide valuable information pertaining to global changes in the redox status of proteins in response to hypoxia...

..0046). Our results provide a strong rationale to monitor SOD and GPX activities of RBC to identify patients who are at risk of developing pneumonitis, and to implement a strategy of increasing the GPX/SOD ratio in order to lower the risk...

..The goal is to broaden our understanding of the significance of clonal suppression of early transformed cells in selenium protection of cancer. ..

..Aim 4 is to study the transcriptional control of GADD153 by selenium. The proposed research is thus designed to examine systemically the impact of GADD153 induction as a result of selenium treatment. ..

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..These studies are designed to apply the in vitro information of Aims 1 and 2 to the in vivo model in order to validate the use of molecular surrogate endpoints in CLA intervention. ..

..The objective is to corroborate the significance of clonal suppression of preneoplastic lesions in selenium protection of cancer. ..