Molecular cancer biology最新文献

{"title":"Women with endometriosis have a higher DNA repair capacity and diminished breast cancer risk.","authors":"Jaime L Matta,&nbsp;Idhaliz Flores,&nbsp;Luisa M Morales,&nbsp;Janice Monteiro,&nbsp;Carolina Alvarez-Garriga,&nbsp;Manuel Bayona","doi":"10.9777/mcb.2013.10005","DOIUrl":"https://doi.org/10.9777/mcb.2013.10005","url":null,"abstract":"<p><strong>Introduction: </strong>Breast cancer (BC) and endometriosis are important reproductive health diseases for women. Although endometriosis is not a malignant condition, some of its characteristics mimic that of a malignancy. Endometriosis is associated with increased risk of certain cancers; however, whether it alters BC risk is unclear. This study evaluates the association of endometriosis and BC and explores whether DNA repair capacity (DRC) plays a role in such a relationship.</p><p><strong>Materials and methods: </strong>A case-control study of 991 women (385 with BC and 606 controls, all recruited over 5 years) was undertaken in Puerto Rico. Eighty participants with self-reported surgically diagnosed endometriosis were identified, 20 of whom also had a diagnosis of BC. Data from a structured questionnaire and DRC measurements were assessed to determine the association between BC, DRC, and endometriosis.</p><p><strong>Results: </strong>Participants with BC cases were 50% less likely to have history of endometriosis (OR = 0.5 95%CI: 0.3, 0.9, <i>p</i> = 0.038) than women without BC controls. Findings that did not reach statistical significance included the following: women with history of endometriosis had a slightly higher DRC level than those without it; BC cases and history of endometriosis were less likely to have had endometriosis diagnosis before age 38 as compared to controls with endometriosis.</p><p><strong>Discussion: </strong>Here we report an inverse association between endometriosis and BC, the former possibly conferring a protective effect on the latter. Although the mechanisms involved are unknown they may include protection provided by higher DRC and or hormonal treatments for endometriosis. A larger sample of endometriosis cases is necessary to confirm these results and answer the question of whether a higher DRC capacity may contribute to this potential protection, and to identify other factors at play.</p>","PeriodicalId":90655,"journal":{"name":"Molecular cancer biology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2013-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4248303/pdf/nihms593531.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32879528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational and synthetic studies towards improving rescinnamine as an inducer of MSH2-dependent apoptosis in cancer treatment","authors":"Elshimaa M. N. Abdelhafez, A. Diamanduros, Lacramioara Negureanu, Yan Luy, J. Bean, K. Zielke, B. Crowe, A. Vasilyeva, J. Clodfelter, O. Aly, G. E. Abuo-Rahma, K. Scarpinato, F. Salsbury, S. King","doi":"10.9777/MCB.V1I1.42","DOIUrl":"https://doi.org/10.9777/MCB.V1I1.42","url":null,"abstract":"We, and others, have previously shown that mismatch repair proteins, in addition to their repair function, contribute to cell death initiation. In response to some drugs, this cell death activity is independent of the repair function of the proteins. Rescinnamine, a derivative of the indole alkaloid reserpine, a drug used to treat hypertension several decades ago, was shown to target the cell death-initiating activity of mismatch repair proteins. When used in animals, the hypotensive action of this drug prevents applying appropriate concentrations for statistically significant tumor reduction. Using a combination of computational modeling, chemical synthesis and cell assays, we determine how rescinnamine can be structurally modified and what effect these modifications have on cell survival. These results inform further computational modeling to suggest new synthetic lead molecules to move toward further biological testing.","PeriodicalId":90655,"journal":{"name":"Molecular cancer biology","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2013-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90077740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential expression of DNA repair genes in Hispanic women with breast cancer.","authors":"Jaime Matta,&nbsp;Luisa Morales,&nbsp;Julie Dutil,&nbsp;Manuel Bayona,&nbsp;Carolina Alvarez,&nbsp;Erick Suarez","doi":"10.9777/mcb.2013.10006","DOIUrl":"https://doi.org/10.9777/mcb.2013.10006","url":null,"abstract":"<p><p>Previous studies have found a link between a low DNA repair capacity (DRC) level and increased risk for breast cancer (BC). A recent study by Matta et al. 2012 showed that women with BC have an average reduction of 60% in DRC compared to controls (<i>P</i> < 0.001). Using the same group of Hispanic women, we selected a subgroup of cases (n=35) and controls (n=2) who donated their tumors and normal tissue for performing molecular studies in order to 1) compare the expression of DNA repair genes in breast tissue between BC cases and controls without this disease, 2) assess the correlation between gene expression and DRC levels, 3) examine whether DRC levels are associated with tumor DNA repair gene expression profiling when women were stratified according to their hormone receptor status. DRC levels were measured in lymphocytes by means of a host-cell reactivation assay. Gene expression levels were measured in tumors by means of DNA microarray analysis. Twenty-one DNA repair genes were found to be differentially and significantly expressed in women with BC. Those candidate genes were <i>CHEK2, EME1 (MMS4L), ERCC3 (XPB), FANCM, H2AFX (H2AX), HMGB1, HUS1, MBD4, NEIL3, PCNA, RAD1, RAD23B, RAD51, RAD54B, RDM1 (RAD52B), SHFM1 (DSS1), TP1, UBE2N</i> (<i>UBC13</i>) <i>and XRCC5 (Ku80)</i>. Most DNA repair genes (n=18 or 82%) were overexpressed, ranging from 3.76-fold (<i>RDM1</i>) to 1.47-fold (<i>XRCC5</i>). Only 4 genes (18%) were underexpressed, ranging from 62% (<i>SAPCD1</i>) to 25% (<i>RAD23B</i>). Statistically significant positive correlations between DRC level and gene expression were found for the <i>RAD51, FANCB</i> and <i>FANCA</i> genes. We discuss the clinical and translational significance of these findings. Our results support the usefulness of studying DNA repair as a measure of BC risk. This study also provides a list of candidate DNA repair genes that might be associated with dysregulation of DNA repair in breast cancer.</p>","PeriodicalId":90655,"journal":{"name":"Molecular cancer biology","volume":"1 1","pages":"54"},"PeriodicalIF":0.0,"publicationDate":"2013-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4189824/pdf/nihms593535.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32742489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational and synthetic studies towards improving rescinnamine as an inducer of MSH2-dependent apoptosis in cancer treatment.","authors":"ElShimaa M N AbdelHafez,&nbsp;Andrew Diamanduros,&nbsp;Lacramioara Negureanu,&nbsp;Yan Luy,&nbsp;J Hayley Bean,&nbsp;Katherine Zielke,&nbsp;Brittany Crowe,&nbsp;Aksana Vasilyeva,&nbsp;Jill E Clodfelter,&nbsp;Omar M Aly,&nbsp;Gamal El-Din A A Abuo-Rahma,&nbsp;Karin D Scarpinato,&nbsp;Freddie R Salsbury,&nbsp;S Bruce King","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>We, and others, have previously shown that mismatch repair proteins, in addition to their repair function, contribute to cell death initiation. In response to some drugs, this cell death activity is independent of the repair function of the proteins. Rescinnamine, a derivative of the indole alkaloid reserpine, a drug used to treat hypertension several decades ago, was shown to target the cell death-initiating activity of mismatch repair proteins. When used in animals, the hypotensive action of this drug prevents applying appropriate concentrations for statistically significant tumor reduction. Using a combination of computational modeling, chemical synthesis and cell assays, we determine how rescinnamine can be structurally modified and what effect these modifications have on cell survival. These results inform further computational modeling to suggest new synthetic lead molecules to move toward further biological testing.</p>","PeriodicalId":90655,"journal":{"name":"Molecular cancer biology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4254817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32888966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}