The Experts below are selected from a list of 1209 Experts worldwide ranked by ideXlab platform
Fadlo R. Khuri - One of the best experts on this subject based on the ideXlab platform.
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The dawn of a revolution in personalized Lung Cancer Prevention.
Cancer prevention research (Philadelphia Pa.), 2011Co-Authors: Fadlo R. KhuriAbstract:Lung Cancer Prevention and early detection, which have fallen on hard times for more than the past 20 years, seem to have turned a corner toward better times ahead. Exciting new results of randomized controlled trials that targeted the arachidonic acid pathway, including a celecoxib trial reported by Mao and colleagues in this issue of the journal (beginning on page 984) and a trial of the prostacyclin analog iloprost, complement recently reported 20%-30% Lung Cancer mortality reductions, either with aspirin in targeting the arachidonic acid pathway or with computed tomography screening. The new results show encouraging activity personalized to former smokers and/or people expressing predictive biomarkers. These trials and technological advances in molecular profiling and imaging herald substantial clinical advances on the horizon of this field.
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Molecularly Targeted Approaches to the ChemoPrevention of Lung Cancer
Clinical Cancer Research, 2004Co-Authors: Fadlo R. Khuri, Victor CohenAbstract:Large, randomized trials have been conducted in the primary Prevention of Lung Cancer using micronutrients or derivative agents for which epidemiological data suggested a potential role in Lung Cancer Prevention. The disappointing primary Prevention trials of β-carotene, α-tocopherol, and retinyl palmitate have led to the development of a more compact, biomarker-driven series of translational trials of Lung Cancer Prevention that target reversal of premalignancy as the primary end point. Serial trials of 13- cis- retinoic acid (isotretinoin) and other retinoids have failed to show a difference in reversal of premalignancy in active smokers or in second primary tumor Prevention. However, a trial of 9- cis- retinoic acid, a pan retinoid/rexinoid agonist, showed up-regulation of retinoic acid receptor β ( RAR- β), a potentially important intermediate marker of response in Lung Cancer premalignancy. Other planned or ongoing trials currently target important molecular markers of Lung carcinogenesis and progression including cyclooxygenase-2, the ras -signaling pathway through farnesyl transferase inhibitors, and the tyrosine kinase/epidermal growth factor receptor pathway (gefitinib, erlotinib). Early results of bioadjuvant trials in head and neck Cancer suggest that combination chemoPrevention will ultimately be an important option.
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Molecularly targeted approaches to the chemoPrevention of Lung Cancer.
Clinical cancer research : an official journal of the American Association for Cancer Research, 2004Co-Authors: Fadlo R. Khuri, Victor CohenAbstract:Large, randomized trials have been conducted in the primary Prevention of Lung Cancer using micronutrients or derivative agents for which epidemiological data suggested a potential role in Lung Cancer Prevention. The disappointing primary Prevention trials of beta-carotene, alpha-tocopherol, and retinyl palmitate have led to the development of a more compact, biomarker-driven series of translational trials of Lung Cancer Prevention that target reversal of premalignancy as the primary end point. Serial trials of 13-cis-retinoic acid (isotretinoin) and other retinoids have failed to show a difference in reversal of premalignancy in active smokers or in second primary tumor Prevention. However, a trial of 9-cis-retinoic acid, a pan retinoid/rexinoid agonist, showed up-regulation of retinoic acid receptor beta (RAR-beta), a potentially important intermediate marker of response in Lung Cancer premalignancy. Other planned or ongoing trials currently target important molecular markers of Lung carcinogenesis and progression including cyclooxygenase-2, the ras-signaling pathway through farnesyl transferase inhibitors, and the tyrosine kinase/epidermal growth factor receptor pathway (gefitinib, erlotinib). Early results of bioadjuvant trials in head and neck Cancer suggest that combination chemoPrevention will ultimately be an important option.
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Primary and Secondary Prevention of Non–Small-Cell Lung Cancer: The SPORE Trials of Lung Cancer Prevention
Clinical Lung Cancer, 2003Co-Authors: Fadlo R. KhuriAbstract:The aims of chemoPrevention in Lung Cancer are to prevent the appearance of disease (primary Prevention) and to stop or reverse the progression of premalignant lesions (secondary Prevention). Until recently, there was little hope that these goals could be attained. However, the results achieved with tamoxifen in the Prevention of breast Cancer, and the emergence of new therapies specifically targeted to molecules involved in the pathogenesis of Lung Cancer have set the stage for investigation of these agents for chemoPrevention of Lung Cancer. Two of these new molecular targeted agents are gefitinib, an inhibitor of epidermal growth factor receptor-tyrosine kinase activity, and tipifarnib (R115777, Zarnestra ), an inhibitor of the farnesyltransferase enzyme, which is required for the proper localization and function of the ras oncogene. Tumor responses and disease stabilization have been achieved with both agents in clinical trials. In the Iressa Dose Evaluation in Advanced Lung Cancer (IDEAL)-1 and IDEAL-2 phase II trials, gefitinib was demonstrated to be effective for disease control in patients with advanced non-small-cell Lung Cancer. The SPORE (Specialized Program of Research Excellence) Trials of Lung Cancer Prevention (STOP) are 2 parallel studies that will investigate the potential effectiveness of gefitinib and tipifarnib in preventing the appearance and progression of premalignant lesions in former or current smokers with a history of smoking-related Cancer. These trials should provide information not only about the potential role of gefitinib and tipifarnib in Lung Cancer chemoPrevention, but also about the molecular changes that underlie tumorigenesis and that may serve as markers of disease progression. The STOP trial objectives are to evaluate the effect of gefitinib and tipifarnib on histologic and biologic parameters in patients with evidence of sputum atypia, to evaluate various parameters as potential predictors of the effectiveness of these agents, and to evaluate the tolerability of these agents over a 6-month course of treatment. Histologic response, defined as Prevention of appearance or progression of premalignant lesions, is the primary endpoint of these trials. New targeted molecular therapies such as gefitinib and tipifarnib may offer the opportunity to make chemoPrevention a viable treatment modality in Lung Cancer as well as in other human solid tumors.
Christine A. Kennedy - One of the best experts on this subject based on the ideXlab platform.
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Revealed preference valuation compared to contingent valuation: radon-induced Lung Cancer Prevention.
Health economics, 2002Co-Authors: Christine A. KennedyAbstract:This paper explores and compares two tools of economic valuation, revealed preference and contingent valuation, with the purpose of ultimately informing the use of two methods of economic evaluation, CEA and CBA. The valuation methods are applied to empirical data for radon-induced Lung Cancer Prevention. However, only the single bound CV and the subjective revealed preference estimates have overlapping confidence intervals, indicating that they do have external validity as assessed by convergent validity. The revealed preference subjective risk valuation was (180 pounds sterling (144 pounds sterling, 247 pounds sterling)) and the single bounded contingent valuation estimate was (269 pounds sterling (201 pounds sterling, 343 pounds sterling)).
Ethan Dmitrovsky - One of the best experts on this subject based on the ideXlab platform.
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Abstract CN05-03: Cooperation between a rexinoid and EGFR-TKI for Lung Cancer Prevention via Cyclin D1 destabilization
Chemoprevention and Biological Therapies, 2015Co-Authors: Konstantin H Dragnev, Sarah J. Freemantle, Vincent A. Memoli, Samuel Waxman, Ethan DmitrovskyAbstract:We previously reported that both nuclear retinoic acid receptor (RAR, retinoid) and retinoid X receptor (RXR, rexinoid) agonists can trigger proteasomal degradation of cyclins. This confers check point arrest and repair of carcinogenic DNA damage in bronchial epithelial cells. Mechanisms responsible for this induced degradation were discovered. These included ubiquitin-dependent as well as ISG15-dependent programs that independently destabilized expression of cyclin D1 and other G1 cyclin proteins. The critical receptor that confers this cyclin destabilization was RARβ. Yet, silencing of RARβ; and specifically of the previously unrecognized isoform that we cloned and designated as RARβ1 likely accounts for clinical resistance to classical retinoids (like 13-cis-retinoic acid and all-trans-retinoic acid) in Lung carcinogenesis. We sought to learn whether RXR/RAR heterodimer complex activation with a rexinoid was able to trigger cyclin destabilization. This was found to be the case in in vitro studies. This finding implied that the same pathway would be engaged in the in vivo setting. To establish if this occurs, we engineered transgenic mice independently with human surfactant C-driven wild-type cyclin E or a proteasome-degradation resistant cyclin E species. This mouse model was developed because human pre-malignant and malignant Lung lesions frequently deregulate cyclin expression. Intriguingly, these mice recapitulated many features of Lung carcinogenesis found in patients. Neoplastic changes were enhanced by transgenic expression of the degradation-resistant cyclin E species. We built on this finding by showing that a rexinoid and an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) each chemoprevented Lung Cancers in vinyl carbamate-induced Lung tumors within strain A/J mice. Notably, the rexinoid was more potent that the EGFR-TKI in conferring this chemoPrevention. Both agents also reduced cyclin expression, but did so through distinct mechanisms. We sought to learn if a rexinoid (bexarotene) cooperated with an EGFR-TKI (erlotinib) in exerting anti-tumorigenic effects in Lung Cancer. Cooperation between these agents was found in both murine and human Lung Cancer cells and even in those cells that exhibited KRAS/p53 mutations. Over the past decade, we translated this work into the Cancer clinic through a series of five clinical trials that moved this work through successive phase 0, phase I, and phase II trials of Lung and aerodigestive tract Cancers. In window of opportunity trials, pharmacodynamic responses (cyclin repression and induced necrosis and inflammatory responses) were seen when intratumoral levels of these drugs were comparable to those necessary to trigger in vitro effects. A phase II trial in heavily pre-treated stage IV non-small cell Lung Cancer (NSCLC) cases was performed. EGFR and cyclin expression profiles as well as KRAS mutations were searched for in these NSCLC cases. Findings revealed substantial cyclin repression and reduction of Lung Cancer growth by combined therapy with a rexinoid (bexarotene) and EGFR-TKI (erlotinib). Cyclins were repressed while necrosis and inflammation were induced in post-treatment versus pre-treatment Lung tumor biopsies obtained in this window of opportunity trial. Objective anti-tumor responses occurred whether or not KRAS or activating EGFR mutations were detected. This refractory NSCLC trial had 3 major clinical responses (2 had KRAS or EGFR mutations) with prolonged survival (583, 665, and 1460+ days, respectively). Median survival was 22 weeks (16 weeks for controls). Hypertriglyceridemia or rash significantly increased median overall survival to 24 weeks. Thus, this combination regimen revealed substantial clinical anti-tumor activity against NSCLCs. Taken together, these findings indicate that cooperation between a rexinoid and EGFR-TKI can chemoprevent and treat Lung Cancers by causing cyclin destabilization. These agents are also useful tools to identify other antineoplastics that repress Lung Cancers by destabilizing cyclin expression or by inhibiting their associated kinases. Evidence for this will be presented in this session. Citation Format: Konstantin H. Dragnev, Vincent Memoli, Sarah J. Freemantle, Samuel Waxman, Ethan Dmitrovsky. Cooperation between a rexinoid and EGFR-TKI for Lung Cancer Prevention via Cyclin D1 destabilization. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr CN05-03.
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Lung Cancer Prevention: the guidelines.
Chest, 2003Co-Authors: Konstantin H Dragnev, Diane Stover, Ethan DmitrovskyAbstract:Lung carcinogenesis is a chronic and multi-step process resulting in malignant Lung tumors. This progression from normal to neoplastic pulmonary cells or tissues could be arrested or reversed through pharmacologic treatments, which are known as Cancer chemoPrevention. These therapeutic interventions should reduce or avoid the clinical consequences of Lung Cancer by treating early neoplastic lesions before the development of clinically evident signs or symptoms of malignancy. Preclinical, clinical, and epidemiologic findings relating to different classes of candidate chemopreventive agents provide strong support for Lung Cancer Prevention as an attractive therapeutic strategy. Smoking Prevention and smoking cessation represent an essential approach to reduce the societal impact of tobacco carcinogenesis. However, even if all the goals of the national antismoking efforts were met, there still would be a large population of former smokers who would be at increased risk for Lung Cancers. Lung Cancer also can occur in those persons who never have smoked. This article focuses on what is now known about pharmacologic strategies for Lung Cancer Prevention. Randomized clinical trials using beta-carotene, retinol, isotretinoin or N-acetyl-cysteine did not show benefit for primary and tertiary Lung Cancer Prevention. There is also evidence that the use of beta-carotene and isotretinoin for Lung Cancer chemoPrevention in high-risk individuals may increase the risk for Lung Cancer, especially in individuals who continue to smoke. There is a need for relevant in vitro models to identify pathways that activate chemopreventive effects in the Lung. An improved understanding of Cancer Prevention mechanisms should aid in the design of clinical trials and in the validation of candidate chemopreventive targets as well as the discovery of new targets. Until such studies are completed, no agent or combination of agents should be used for Lung Cancer Prevention outside of a clinical trial.
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Lung Cancer Prevention the guidelines
Chest, 2003Co-Authors: Konstantin H Dragnev, Diane E. Stover, Ethan DmitrovskyAbstract:Lung carcinogenesis is a chronic and multi-step process resulting in malignant Lung tumors. This progression from normal to neoplastic pulmonary cells or tissues could be arrested or reversed through pharmacologic treatments, which are known as Cancer chemoPrevention. These therapeutic interventions should reduce or avoid the clinical consequences of Lung Cancer by treating early neoplastic lesions before the development of clinically evident signs or symptoms of malignancy. Preclinical, clinical, and epidemiologic findings relating to different classes of candidate chemopreventive agents provide strong support for Lung Cancer Prevention as an attractive therapeutic strategy. Smoking Prevention and smoking cessation represent an essential approach to reduce the societal impact of tobacco carcinogenesis. However, even if all the goals of the national antismoking efforts were met, there still would be a large population of former smokers who would be at increased risk for Lung Cancers. Lung Cancer also can occur in those persons who never have smoked. This article focuses on what is now known about pharmacologic strategies for Lung Cancer Prevention. Randomized clinical trials using β-carotene, retinol, isotretinoin or N-acetyl-cysteine did not show benefit for primary and tertiary Lung Cancer Prevention. There is also evidence that the use of β-carotene and isotretinoin for Lung Cancer chemoPrevention in high-risk individuals may increase the risk for Lung Cancer, especially in individuals who continue to smoke. There is a need for relevant in vitro models to identify pathways that activate chemopreventive effects in the Lung. An improved understanding of Cancer Prevention mechanisms should aid in the design of clinical trials and in the validation of candidate chemopreventive targets as well as the discovery of new targets. Until such studies are completed, no agent or combination of agents should be used for Lung Cancer Prevention outside of a clinical trial.
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Cancer and Aging Handbook: Research and Practice - Lung Cancer Prevention: the guidelines
Chest, 2003Co-Authors: Konstantin H Dragnev, Diane E. Stover, Ethan DmitrovskyAbstract:Lung carcinogenesis is a chronic and multi-step process resulting in malignant Lung tumors. This progression from normal to neoplastic pulmonary cells or tissues could be arrested or reversed through pharmacologic treatments, which are known as Cancer chemoPrevention. These therapeutic interventions should reduce or avoid the clinical consequences of Lung Cancer by treating early neoplastic lesions before the development of clinically evident signs or symptoms of malignancy. Preclinical, clinical, and epidemiologic findings relating to different classes of candidate chemopreventive agents provide strong support for Lung Cancer Prevention as an attractive therapeutic strategy. Smoking Prevention and smoking cessation represent an essential approach to reduce the societal impact of tobacco carcinogenesis. However, even if all the goals of the national antismoking efforts were met, there still would be a large population of former smokers who would be at increased risk for Lung Cancers. Lung Cancer also can occur in those persons who never have smoked. This article focuses on what is now known about pharmacologic strategies for Lung Cancer Prevention. Randomized clinical trials using β-carotene, retinol, isotretinoin or N-acetyl-cysteine did not show benefit for primary and tertiary Lung Cancer Prevention. There is also evidence that the use of β-carotene and isotretinoin for Lung Cancer chemoPrevention in high-risk individuals may increase the risk for Lung Cancer, especially in individuals who continue to smoke. There is a need for relevant in vitro models to identify pathways that activate chemopreventive effects in the Lung. An improved understanding of Cancer Prevention mechanisms should aid in the design of clinical trials and in the validation of candidate chemopreventive targets as well as the discovery of new targets. Until such studies are completed, no agent or combination of agents should be used for Lung Cancer Prevention outside of a clinical trial.
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Evidence for the Epidermal Growth Factor Receptor As a Target for Lung Cancer Prevention
Clinical cancer research : an official journal of the American Association for Cancer Research, 2002Co-Authors: Fulvio Lonardo, Konstantin H Dragnev, Sarah J. Freemantle, Natalie Memoli, David Sekula, Elisabeth Knauth, Jean Beebe, Ethan DmitrovskyAbstract:Purpose: There is a need to identify Lung Cancer Prevention mechanisms. All- trans -retinoic acid (RA) was reported previously to inhibit N -nitrosamine-4-(methylnitrosamino)-1-(3 pyridyl)-1-butanone (NNK) carcinogenic transformation of BEAS-2B human bronchial epithelial cells (J. Langenfeld et al ., Oncogene, 13: 1983–1990, 1996). This study was undertaken to identify pathways targeted during this chemoPrevention. Experimental Design: Because epidermal growth factor receptor (EGFR) overexpression is frequent in non-small cell Lung Cancers (NSCLC) and bronchial preneoplasia, BEAS-2B cells, carcinogen-transformed BEAS-2BNNK cells, and retinoid chemoprevented BEAS-2BNNK RA cells were each examined for EGFR expression. Whether RA treatment regulated directly EGFR expression or reporter plasmid activity was studied. RA effects on epidermal growth factor (EGF) induction of EGFR-phosphotyrosine levels, cyclin D1 expression and mitogenesis were examined in BEAS-2B cells. Results: Findings reveal that NNK-mediated transformation of BEAS-2B cells increased EGFR expression. RA treatment repressed EGFR expression and reporter plasmid activity in these cells. This treatment reduced EGF-dependent mitogenesis as well as EGFR-associated phosphotyrosine levels and cyclin D1 expression. These findings extend prior work by highlighting EGFR as a chemoPrevention target in the Lung. Notably, RA treatment prevented transformation as well as outgrowth of EGFR overexpressing bronchial epithelial cells, despite NNK exposure. After acute NNK exposure, p53-induced species that appear after DNA damage or oxidative stress were evident before an observed increase in EGFR expression. Conclusions: These findings indicate how effective chemoPrevention prevents carcinogenic transformation of bronchial epithelial cells when repair of genomic damage does not select against EGFR overexpressing cells. This implicates EGFR as a chemoPrevention target in the carcinogen-exposed bronchial epithelium.
S. Pamela Shiao - One of the best experts on this subject based on the ideXlab platform.
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Abstract 5050: A meta-analysis of lifestyle factors with MPO and GSTM1 human genes in Lung Cancer Prevention
Prevention Research, 2014Co-Authors: S. Pamela Shiao, Maria SuarezAbstract:Purpose: Lung Cancer (LC) is a worldwide public health problem and a leading cause of death in both men and women. Its development is attributed to epigenetic factors, including smoking, diet, and occupation that can be modified. Glutathione S-transferase that belongs to the mu class (GSTM1) and myeloperoxidase (MPO) gene polymorphisms have been cumulating in the literature, associating lifestyle factors and LC development. Thus, a meta-analysis was conducted to examine the associations of lifestyle factors with GSTM1 and MPO genes for LC Prevention. Procedure: Literature searcheswere completed by searching at three different times using keyword related to human GSTM1, MPO, and LC. Quality of the studies were rated based the standards of Quality of Reporting of Meta-analysis. Inter-rater evaluation on data coding was completed to ensure data accuracy. Pooled relative risks (RR) was computed to determine the association of factors with LC. Findings: Preliminary analyses included 28,831 cases and 35,069 controls associating smoking with LC in 98 studies; with 5,938 cases versus 6,668 controls nested in 20 studies with MPO gene counts, and 7,101 cases and 9,396 controls nested in 32 studies with GSTM1 gene counts respectively. Smoking status was associated with increased LC risk in all populations (RR = 1.40, p Conclusion: Following the meta-analysis of these studies, it can be recommended that primary epigenetic Prevention of LC could include environment free from tobacco smoking and having a diet rich in isothiocyanates or vegetable intake. These preventive measures are important in attenuating oxidative stress for healthy methylation pathways to reduce the risk factors of LC. Citation Format: PoJui Paula Yu, S. Pamela Shiao, Maria Suarez. A meta-analysis of lifestyle factors with MPO and GSTM1 human genes in Lung Cancer Prevention. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5050. doi:10.1158/1538-7445.AM2014-5050
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Abstract B07: A meta-analysis of GSTM1 human genome as risk factor in Lung Cancer Prevention
Behavioral and Social Science, 2013Co-Authors: Maria Suarez, S. Pamela Shiao, Mildred C. Gonzales, Amanda Lie, Ching-yi ChiuAbstract:Purpose: Lung Cancer is the highest cause of Cancer related death in the United States. Its development is attributed to environmental and genetic factors. Smoking, diet, and occupation are environmental factors that can affect its development. Besides the environmental elements, the genetic aspect of this risk has also been identified as a major factor. Polymorphism in an individual9s genotype has been recognized as a possible risk for Lung Cancer. GSTM1 has been one of the genes being studied with regards to genetic polymorphism affecting Lung Cancer development. A meta-analysis was conducted to examine the association of GSTM1 human genome as a risk factor for Lung Cancer. Procedure: Literature searches were completed by searching at three different times using keyword related to human GSTM1 and Lung Cancer. The searches generated 326 papers. The preliminary count includes 138 case-control studies. Quality rating of the literatures included will be based on Quality of Reporting of Meta-analysis (QUOROM). GSTM1 genes are categorized into present and null deletion genotype. Each category will be grouped by country and ethnicity. Inter-rater evaluation will be done for quality rating and gene count to ensure accurate appraisal of data collected. Pooled relative risks will be computed for each genotype and ethnicity to determine association with Lung Cancer. Findings: With the total cases of 12,288 and control subjects of 16,836, this meta-analysis is able to ascertain the association of GSTM1 with Lung Cancer risk. The present genotype of GSTM1 has been established as protective in nature (P Conclusion: The association between GSTM1 and Lung Cancer has been established through this meta-analysis. The results from this meta-analysis prompt the need for further studies that examine GSTM1 genotypes with inclusion of more studies for various race-ethnicity groups and countries. GSTM1 present genotype has an essential role in preventing Lung Cancer. There is a need to identify ways to enhance or maintain this GSTM1 genotype in future studies. Dietary intake of cruciferous vegetables is a promising factor in preventing Lung Cancer. Citation Format: Maria Suarez, S. Pamela Shiao, Mildred Gonzales, Amanda Lie, Ching-Yi Chiu. A meta-analysis of GSTM1 human genome as risk factor in Lung Cancer Prevention. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr B07.
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Abstract A02: Meta-analyses of MPO, EGFR, and GSTM1 genes as risk factors for Lung Cancer Prevention
Cancer Prevention Research, 2012Co-Authors: Nick Devries, S. Pamela Shiao, Ching-yi Chiu, Melissa J. Labonte, Linda H. Chiang, Rose SakamotoAbstract:Purpose: The purpose of this meta-analysis was to identify genes that have been associated with Lung Cancer (LC), and the risk factors associated with these genes for Cancer Prevention. LC is the leading cause of Cancer related deaths worldwide. Three genes identified through the genome application framework, and well published in the literature, are Myeloperoxidase (MPO), a receptor for members of the epidermal growth factor (EGFR) family, and a glutathione S-transferase that belongs to the mu class (GSTM1). Findings from previous meta-analyses on this topic published from 10 years ago to 2 years ago were mixed with inconsistent and controversial findings. Since then, additional literature showed identification of the potential risk factors for the application of Cancer genome and LC Prevention. Procedure: On-line literature were searched from PubMed (PM), PM Central, PM Health databases for systematic reviews and meta-analyses by using a variety of combinations of key words about LC genes, Cancer Prevention, human models, and clinical trials. For this analysis, 61 studies were identified that have been published within the last 15 years and included data containing both control and LC cases of human samples. These papers were reviewed and evaluated using the criteria for the quality of studies. These studies included 20, 22, and 19 studies on MPO, EGFR and GSTM1 respectively. Summary of Data Findings: Preliminary analyses included 83,711 cases and 16,256 controls associating these genes with LC; with 6,363, 7,192, and 70,156 LC cases versus 7,3,46, 7,532, and 1,378 controls for MPO, EGFR and GSTM1 respectively. These studies included samples of all races and many ethnicity groups, and both genders. For Prevention, these three genes each have unique metabolic mechanisms and major single nucleotide polymorphisms (SNPs) associated with the prognosis and treatment effects of LC. MPO is released from neutrophils in response to various pulmonary insults such as tobacco smoking and chemicals that produce air populations, thus, smokers and industrial workers have worse prognosis. Specifically, the MPO SNP, G-463A (rs2333227) has been significantly associated with LC risk. EGFR protein production including activating somatic mutations (exon 19 deletion and exon 21 L858R) may be different across gender and racial ethnic groups and demonstrate different sensitivity in non-smokers. Thus, Prevention and treatments targeting EGFR may be considered in preference to other Cancer treatments. Those with LC and SNPs of GSTM1 type have been found to be highly influenced by the dietary intake of cruciferous vegetables or fruits and green teas for the prognosis, especially for individuals who are susceptible for oxidative stress and oxidative DNA damage. Conclusion: Following analysis of these studies, it can be recommended that primary Prevention of LC could include having a diet rich in antioxidants, and avoiding tobacco smoking and air pollution in environmental exposures. Meta-analysis of these studies has important impact for healthy lifestyles, health habits and screening. Maintenance of healthy lifestyles includes avoiding tobacco smoking or second hand smoking, and inhaling air pollutants; and taking a nutritional diet rich in antioxidants such as cruciferous vegetables or fruits and green teas. These preventive application measures are important in attenuating oxidative stress and DNA damage to reduce the risk factors of LC for the general public. Citation Format: Nick DeVries, S. Pamela Shiao, Melissa J. LaBonte, Ching-Yi Chiu, Linda H. Chiang, Rose Sakamoto. Meta-analyses of MPO, EGFR, and GSTM1 genes as risk factors for Lung Cancer Prevention. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A02.
Maria Suarez - One of the best experts on this subject based on the ideXlab platform.
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Abstract 5050: A meta-analysis of lifestyle factors with MPO and GSTM1 human genes in Lung Cancer Prevention
Prevention Research, 2014Co-Authors: S. Pamela Shiao, Maria SuarezAbstract:Purpose: Lung Cancer (LC) is a worldwide public health problem and a leading cause of death in both men and women. Its development is attributed to epigenetic factors, including smoking, diet, and occupation that can be modified. Glutathione S-transferase that belongs to the mu class (GSTM1) and myeloperoxidase (MPO) gene polymorphisms have been cumulating in the literature, associating lifestyle factors and LC development. Thus, a meta-analysis was conducted to examine the associations of lifestyle factors with GSTM1 and MPO genes for LC Prevention. Procedure: Literature searcheswere completed by searching at three different times using keyword related to human GSTM1, MPO, and LC. Quality of the studies were rated based the standards of Quality of Reporting of Meta-analysis. Inter-rater evaluation on data coding was completed to ensure data accuracy. Pooled relative risks (RR) was computed to determine the association of factors with LC. Findings: Preliminary analyses included 28,831 cases and 35,069 controls associating smoking with LC in 98 studies; with 5,938 cases versus 6,668 controls nested in 20 studies with MPO gene counts, and 7,101 cases and 9,396 controls nested in 32 studies with GSTM1 gene counts respectively. Smoking status was associated with increased LC risk in all populations (RR = 1.40, p Conclusion: Following the meta-analysis of these studies, it can be recommended that primary epigenetic Prevention of LC could include environment free from tobacco smoking and having a diet rich in isothiocyanates or vegetable intake. These preventive measures are important in attenuating oxidative stress for healthy methylation pathways to reduce the risk factors of LC. Citation Format: PoJui Paula Yu, S. Pamela Shiao, Maria Suarez. A meta-analysis of lifestyle factors with MPO and GSTM1 human genes in Lung Cancer Prevention. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5050. doi:10.1158/1538-7445.AM2014-5050
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Abstract B07: A meta-analysis of GSTM1 human genome as risk factor in Lung Cancer Prevention
Behavioral and Social Science, 2013Co-Authors: Maria Suarez, S. Pamela Shiao, Mildred C. Gonzales, Amanda Lie, Ching-yi ChiuAbstract:Purpose: Lung Cancer is the highest cause of Cancer related death in the United States. Its development is attributed to environmental and genetic factors. Smoking, diet, and occupation are environmental factors that can affect its development. Besides the environmental elements, the genetic aspect of this risk has also been identified as a major factor. Polymorphism in an individual9s genotype has been recognized as a possible risk for Lung Cancer. GSTM1 has been one of the genes being studied with regards to genetic polymorphism affecting Lung Cancer development. A meta-analysis was conducted to examine the association of GSTM1 human genome as a risk factor for Lung Cancer. Procedure: Literature searches were completed by searching at three different times using keyword related to human GSTM1 and Lung Cancer. The searches generated 326 papers. The preliminary count includes 138 case-control studies. Quality rating of the literatures included will be based on Quality of Reporting of Meta-analysis (QUOROM). GSTM1 genes are categorized into present and null deletion genotype. Each category will be grouped by country and ethnicity. Inter-rater evaluation will be done for quality rating and gene count to ensure accurate appraisal of data collected. Pooled relative risks will be computed for each genotype and ethnicity to determine association with Lung Cancer. Findings: With the total cases of 12,288 and control subjects of 16,836, this meta-analysis is able to ascertain the association of GSTM1 with Lung Cancer risk. The present genotype of GSTM1 has been established as protective in nature (P Conclusion: The association between GSTM1 and Lung Cancer has been established through this meta-analysis. The results from this meta-analysis prompt the need for further studies that examine GSTM1 genotypes with inclusion of more studies for various race-ethnicity groups and countries. GSTM1 present genotype has an essential role in preventing Lung Cancer. There is a need to identify ways to enhance or maintain this GSTM1 genotype in future studies. Dietary intake of cruciferous vegetables is a promising factor in preventing Lung Cancer. Citation Format: Maria Suarez, S. Pamela Shiao, Mildred Gonzales, Amanda Lie, Ching-Yi Chiu. A meta-analysis of GSTM1 human genome as risk factor in Lung Cancer Prevention. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr B07.
