Lung cancer chemoprevention

Khuri, Fadlo R.; Lippman, Scott M.

doi:10.1002/(sici)1098-2388(200003)18:2<100::aid-ssu3>3.0.co;2-9

Cited by 26 publications

(11 citation statements)

References 41 publications

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“…Unfortunately, the desired effects of these therapies may be offset by undesirable inflammatory reactions that limit therapy in humans. To reduce the undesirable effects, dietary supplements and anti-oxidants have been increasingly utilized [1][2][3]. They are postulated to reduce the toxic effects of therapy, reduce oxidant stress and enhance the host immune response to some cancers.…”

Section: Introductionmentioning

confidence: 99%

Pyrrolidine dithiocarbamate (PDTC) blocks apoptosis and promotes ionizing radiation-induced necrosis of freshly-isolated normal mouse spleen cells

et al. 2010

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Ionizing radiation (IR) is a pro-oxidant that kills cells by both apoptotic and necrotic mechanisms. Pyrrolidine dithiocarbamate (PDTC) is a thiol-containing compound that may act either as a pro- or anti-oxidant depending on the experimental conditions. This study was designed to determine whether PDTC would reduce or enhance IR-induced cell death of freshly-isolated normal mouse B6/129 spleen cells (NMSC). We determined the effect of increasing doses of IR, PDTC alone and PDTC followed by IR on the viability of NMSC. Annexin V and propidium iodide (Annexin V/PI) staining demonstrated a dose and time-dependent relationship in which PDTC enhanced the percentage of IR-induced apoptotic/necrotic NMSC. Trypan blue dye inclusion confirmed that a loss of membrane integrity was occurring 1 h after incubation with PDTC plus IR. Reduction in the glutathione (GSH)/glutathione disulfide (GSSG) ratio and GSH demonstrated that both IR (8.5 Gy) and PDTC acted as pro-oxidants, but their mechanisms of action differed: In contrast to IR, which promoted p53 activation and caspase 3/7-mediated apoptosis, PDTC inhibited IR-induced p53 and caspase 3/7 activity. However, PDTC increased H(2)O(2) formation and necrosis, resulting in an overall increase in IR-induced cell death. Catalase prevented the PDTC-induced increase in IR cytotoxicity implicating the generation of H(2)O(2) as a major factor in this mechanism. These results demonstrate that in NMSC PDTC acts as pro-oxidant and enhances IR-induced cell cytotoxicity by increasing H(2)O(2)formation and thiol oxidation. As such, they strongly suggest that the use of PDTC as an adjunct to reduce radiation toxicity should be avoided.

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Section: Introductionmentioning

confidence: 99%

Pyrrolidine dithiocarbamate (PDTC) blocks apoptosis and promotes ionizing radiation-induced necrosis of freshly-isolated normal mouse spleen cells

et al. 2010

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“…In both in vivo and in vitro studies, SeM has emerged as one of the most potent agents evaluated as a countermeasure for HZE particle-induced oxidative stress (5). Non-toxic levels of SeM have been shown to have cancer chemopreventive activity (6)(7)(8)(9)(10). SeM is the form of selenium that has been chosen by the National Cancer Institute (NCI) for current studies of selenium as a cancer preventive agent.…”

Section: Introductionmentioning

confidence: 99%

L-selenomethionine modulates high LET radiation-induced alterations of gene expression in cultured human thyroid cells

Stewart

Ware²,

Fortina³

et al. 2006

Oncol Rep

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Abstract. L-selenomethionine (SeM) is emerging as a highly effective protective agent against radiation-induced biological effects. We have shown its protective effect on space radiationinduced death of MCF-10 cells as well as on space radiationinduced transformation of HTori-3 cells. The present study was aimed at elucidation of molecular mechanisms and cellular pathways involved in SeM-mediated radioprotection. Human thyroid epithelial cells (HTori-3 cells), in the presence or absence of SeM, were exposed to a non-toxic or a slightly toxic radiation dose from 1 GeV/n iron ions (10 cGy and 20 cGy, respectively). Total RNA was prepared and changes in gene expression were analyzed using microarray technology. Our analysis has revealed a dramatic effect of SeM on alterations of gene expression caused by space radiation. This study provides a basis for furthering our knowledge about radiation-induced molecular and cellular changes that lead to cellular transformation and death.

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“…In contrast, clinical trials with retinoids and/or Vitamin A derivatives have yielded mixed results. For example, three placebo-controlled trials with etretinate, isotretinoin, and fenretinide, respectively, have shown no improvements in rates of reversal of metaplasia, as recently reviewed by Khuri and Lippman [7]. At the same time, an adjuvant trial in patients with early-stage, resected NSCLC found that retinyl palmitate reduced the time to second tobacco-related primary cancers [8].…”

Section: Introductionmentioning

confidence: 99%

Is voluntary vitamin and mineral supplementation associated with better outcome in non-small cell lung cancer patients?

Jatoi¹,

Williams²,

Nichols³

et al. 2005

Lung Cancer

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Lung cancer chemoprevention

Cited by 26 publications

References 41 publications

Pyrrolidine dithiocarbamate (PDTC) blocks apoptosis and promotes ionizing radiation-induced necrosis of freshly-isolated normal mouse spleen cells

Pyrrolidine dithiocarbamate (PDTC) blocks apoptosis and promotes ionizing radiation-induced necrosis of freshly-isolated normal mouse spleen cells

L-selenomethionine modulates high LET radiation-induced alterations of gene expression in cultured human thyroid cells

Is voluntary vitamin and mineral supplementation associated with better outcome in non-small cell lung cancer patients?

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