International journal of cancer and clinical research最新文献

{"title":"A Derivative of Differentiation-Inducing Factor-3 Inhibits PAK1 Activity and Breast Cancer Cell Proliferation","authors":"Peter O. Oladimeji, Y. Kubohara, H. Kikuchi, Y. Oshima, Courtney Rusch, Rebekah Skerl, M. Diakonova","doi":"10.23937/2378-3419/2/4/1023","DOIUrl":"https://doi.org/10.23937/2378-3419/2/4/1023","url":null,"abstract":"Differentiation-inducing factors 1-3 (DIFs 1-3), chlorinated alkylphenones identified in the cellular slime mold Dictyostelium discoideum, are considered anti-tumor agents because they inhibit proliferation of a variety of mammalian tumor cells in vitro. Although the anti-proliferative effects of DIF-1 and DIF-3 are well-documented, the precise molecular mechanisms underlying the actions of DIFs have not been fully elucidated. In this study, we examined the effects of DIFs and their derivatives on PAK1, a key serine-threonine kinase, which is activated by multiple ligands and regulates cell proliferation. We examined the effect of DIF derivatives on PAK1 kinase activity in cells. We also examined the effect of DIF-3(+1) derivative on PAK1 kinase activity in vitro, cyclin D1 promoter activity and breast cancer cell proliferation. It was found that some derivatives strongly inhibited PAK1 kinase activity in human breast cancer MCF-7 cells stably over expressing PAK1. Among the derivatives, DIF-3(+1) was most potent, which directly inhibited kinase activity of recombinant purified PAK1 in an in vitro kinase assay. Furthermore, DIF-3(+1) strongly inhibited both cyclin D1 promoter activity and proliferation of MCF-7 and T47D breast cancer cells stably over expressing PAK1 in response to prolactin, estrogen, epidermal growth factor and heregulin. In the present study we propose PAK1 as DIF-3(+1) target mediating its anti-proliferative effect.","PeriodicalId":13873,"journal":{"name":"International journal of cancer and clinical research","volume":"6 1","pages":"1 - 6"},"PeriodicalIF":0.0,"publicationDate":"2015-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86695662","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":"Gene-Specific Promoter Methylation Status in Hormone-Receptor-Positive Breast Cancer Associates with Postmenopausal Body Size and Recreational Physical Activity.","authors":"Lauren E McCullough,&nbsp;Jia Chen,&nbsp;Alexandra J White,&nbsp;Xinran Xu,&nbsp;Yoon Hee Cho,&nbsp;Patrick T Bradshaw,&nbsp;Sybil M Eng,&nbsp;Susan L Teitelbaum,&nbsp;Mary Beth Terry,&nbsp;Gail Garbowski,&nbsp;Alfred I Neugut,&nbsp;Hanina Hibshoosh,&nbsp;Regina M Santella,&nbsp;Marilie D Gammon","doi":"10.23937/2378-3419/2/1/1013","DOIUrl":"https://doi.org/10.23937/2378-3419/2/1/1013","url":null,"abstract":"<p><strong>Introduction: </strong>Breast cancer, the leading cancer diagnosis among American women, is positively associated with postmenopausal obesity and little or no recreational physical activity (RPA). However, the underlying mechanisms of these associations remain unresolved. Aberrant changes in DNA methylation may represent an early event in carcinogenesis, but few studies have investigated associations between obesity/RPA and gene methylation, particularly in postmenopausal breast tumors where these lifestyle factors are most relevant.</p><p><strong>Methods: </strong>We used case-case unconditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CI) for the associations between body mass index (BMI=weight [kg]/height [m²]) in the year prior to diagnosis, or RPA (average hours/week), and methylation status (methylated vs. unmethylated) of 13 breast cancer-related genes in 532 postmenopausal breast tumor samples from the Long Island Breast Cancer Study Project. We also explored whether the association between BMI/RPA and estrogen/progesterone-receptor status (ER+PR+ vs. all others) was differential with respect to gene methylation status. Methylation-specific PCR and the MethyLight assay were used to assess gene methylation.</p><p><strong>Results: </strong>BMI 25-29.9kg/m², and perhaps BMI≥30kg/m², was associated with methylated <i>HIN1</i> in breast tumor tissue. Cases with BMI≥30kg/m² were more likely to have ER+PR+ breast tumors in the presence of unmethylated <i>ESR1</i> (OR=2.63, 95% CI 1.32-5.25) and women with high RPA were more likely to have ER+PR+ breast tumors with methylated <i>GSTP1</i> (OR=2.33, 95% CI 0.79-6.84).</p><p><strong>Discussion: </strong>While biologically plausible, our findings that BMI is associated with methylated <i>HIN1</i> and BMI/RPA are associated with ER+PR+ breast tumors in the presence of unmethylated <i>ESR1</i> and methylated <i>GSTP1</i>, respectively, warrant further investigation. Future studies would benefit from enrolling greater numbers of postmenopausal women and examining a larger panel of breast cancer-related genes.</p>","PeriodicalId":13873,"journal":{"name":"International journal of cancer and clinical research","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4440485/pdf/nihms-683885.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33332472","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":"Prognostic Significance of Hormone Receptor (ER/PR) Status Inendometrial Carcinoma in Black Women: Implications with Lymph Node Metastasis","authors":"Shah Manan, Oprea Gabriela, Shafia Saba, Surapaneni Phani Keerthi, Sasidharan Sandeep, J. Sanjay","doi":"10.23937/2378-3419/1410150","DOIUrl":"https://doi.org/10.23937/2378-3419/1410150","url":null,"abstract":"","PeriodicalId":13873,"journal":{"name":"International journal of cancer and clinical research","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78827511","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}