المؤلفون: Merino, Vanessa F., Cho, Soonweng, Nguyen, Nguyen, Sadik, Helen, Narayan, Athira, Talbot, Conover, Cope, Leslie, Zhou, Xian C., Zhang, Zhe, Győrffy, Balázs, Sukumar, Saraswati

المساهمون: U.S. Department of Defense, National Research, Development and Innovation Office

المصدر: Breast Cancer Research ; volume 20, issue 1 ; ISSN 1465-542X

الإتاحة: https://doi.org/10.1186/s13058-018-1068-xTest

مستخلص: The invention generally features compositions and methods that are useful for treating or diagnosing a neoplasia, in particular breast neoplasia. The invention is based in part on the observation that the basic helix loop helix transcription factor HEYL was found to be overexpressed in breast cancer cells. Accordingly, the invention provides therapeutic compositions and methods for altering the levels and expression of HEYL of the invention, thereby treating a neoplasia, as well as compositions and methods for diagnosing a neoplasia.

المؤلفون: Merino, Vanessa F., Cho, Soonweng, Liang, Xiaohui, Park, Sunju, Jin, Kideok, Chen, Qian, Pan, Duojia, Zahnow, Cynthia A., Rein, Alan R., Sukumar, Saraswati

المساهمون: DOD BCRP Center of Excellence, Komen Scholar, DOD BCRP Postdoctoral Fellowship

المصدر: Molecular Oncology ; volume 11, issue 5, page 552-566 ; ISSN 1574-7891 1878-0261

الوصف: Although mutations in the phosphoinositide 3‐kinase catalytic subunit ( PIK 3 CA ) are common in breast cancer, PI 3K inhibitors alone have shown modest efficacy. We sought to identify additional pathways altered in PIK 3 CA ‐mutant tumors that might be targeted in combination with PI 3K inhibitors. We generated two transgenic mouse models expressing the human PIK 3 CA ‐H1047R‐ and the ‐E545K hotspot‐mutant genes in the mammary gland and evaluated their effects on development and tumor formation. Molecular analysis identified pathways altered in these mutant tumors, which were also targeted in multiple cell lines derived from the PIK 3 CA tumors. Finally, public databases were analyzed to determine whether novel pathways identified in the mouse tumors were altered in human tumors harboring mutant PIK 3 CA . Mutant mice showed increased branching and delayed involution of the mammary gland compared to parental FVB /N mice. Mammary tumors arose in 30% of the MMTV ‐ PIK 3 CA ‐H1047R and in 13% of ‐E545K mice. Compared to MMTV ‐Her‐2 transgenic mouse mammary tumors, H1047R tumors showed increased upregulation of Wnt/β‐catenin/Axin2, hepatocyte growth factor (Hgf)/Stat3, insulin‐like growth factor 2 (Igf‐2), and Igf‐1R pathways. Inhibitors of STAT 3, β‐catenin, and IGF ‐1R sensitized H1047R‐derived mouse tumor cells and PIK 3 CA ‐H1047R overexpressing human HS 578T breast cancer cells to the cytotoxic effects of PI 3K inhibitors. Analysis of The Cancer Genome Atlas database showed that, unlike primary PIK 3 CA ‐wild‐type and HER ‐2 + breast carcinomas, PIK 3 CA ‐mutant tumors display increased expression of AXIN 2, HGF , STAT 3, IGF ‐1, and IGF ‐2 mRNA and activation of AKT , IGF 1‐ MTOR , and WNT canonical signaling pathways. Drugs targeting additional pathways that are altered in PIK 3 CA ‐mutant tumors may improve treatment regimens using PI 3K inhibitors alone.

الإتاحة: https://doi.org/10.1002/1878-0261.12053Test

المؤلفون: Zhang, Yinlong, Wei, Jingyan, Liu, Shaoli, Wang, Jing, Han, Xuexiang, Qin, Hao, Lang, Jiayan, Cheng, Keman, Li, Yiye, Qi, Yingqiu, Anderson, Greg J, Sukumar, Saraswati, Li, Suping, Nie, Guangjun

المصدر: Theranostics ; volume 7, issue 5, page 1062-1071 ; ISSN 1838-7640

الإتاحة: https://doi.org/10.7150/thno.17908Test
http://www.thno.org/v07p1062.htmTest

المؤلفون: Downs, Bradley M., Sukumar, Saraswati

المساهمون: Congressionally Directed Medical Research Programs

المصدر: ACS Applied Materials & Interfaces ; volume 14, issue 21, page 24113-24121 ; ISSN 1944-8244 1944-8252

مصطلحات موضوعية: General Materials Science

الإتاحة: https://doi.org/10.1021/acsami.2c03186Test

المؤلفون: Jin, Kideok, Kong, Xiangjun, Shah, Tariq, Penet, Marie-France, Wildes, Flonne, Sgroi, Dennis C., Ma, Xiao-Jun, Huang, Yi, Kallioniemi, Anne, Landberg, Goran, Bieche, Ivan, Wu, Xinyan, Lobie, Peter E., Davidson, Nancy E., Bhujwalla, Zaver M., Zhu, Tao, Sukumar, Saraswati

المصدر: Proceedings of the National Academy of Sciences of the United States of America, 2012 Feb . 109(8), 2736-2741.

الوصول الحر: https://www.jstor.org/stable/41506837Test

المؤلفون: Maruyama, Reo, Shipitsin, Michail, Choudhury, Sibgat, Wu, Zhenhua, Protopopov, Alexei, Yao, Jun, Lo, Pang-Kuo, Bessarabova, Marina, Ishkin, Alex, Nikolsky, Yuri, Liu, X. Shirley, Sukumar, Saraswati, Polyak, Kornelia

المصدر: Proceedings of the National Academy of Sciences of the United States of America, 2012 Feb . 109(8), 2820-2824.

الوصول الحر: https://www.jstor.org/stable/41506851Test

المؤلفون: de Groot, Jolien S, Moelans, CB, Elias, Sjoerd G, Fackler, Mary Jo, van Domselaar, Robert, Suijkerbuijk, Karijn P M, Witkamp, Arjen J, Sukumar, Saraswati, van Diest, Paul J, van der Wall, E.

المساهمون: Pathologie, Pathologie Groep Van Diest, Cancer, Epi Kanker Team A, JC onderzoeksprogramma Kanker, Unit Opleiding Aios, MS CGO, Divisie Beeld & Oncologie

مصطلحات موضوعية: Journal Article

الوصف: INTRODUCTION: Nipple fluid aspiration provides direct non-invasive sampling of fluid from the mammary ductal system, where the majority of breast cancers originate. DNA promoter hypermethylation ("methylation") occurs early and at high frequency in breast carcinogenesis, bearing the potential as a biomarker for cancer detection at its earliest stages. We assessed methylation in nipple fluid from breasts of healthy women, of women with sporadic breast cancer and of their contralateral breasts. Our goal was to investigate whether nipple fluid can be used as a reliable methylation biomarker source. METHODS: Methylation levels of 13 genes were analysed by quantitative multiplex-methylation specific PCR (QM-MSP) in nipple fluid samples from breasts of healthy women, and from the affected and contralateral breasts of breast cancer patients. RESULTS: Methylation analysis of the low-volume nipple fluid samples was feasible. Despite the generally low methylation levels, cancerous and healthy breasts nipple fluid could be discriminated with an area under the receiver operating characteristic curve (AUC) of 0.64 (p<0.01) based on a multivariate model including AKR1B1, ALX1, RASSF1A and TM6SF1. Within-patient differences between cancerous and contralateral nipple fluid samples were less prominent. CONCLUSIONS: Cancerous nipple fluid contains increased levels of methylation of tumor suppressor genes that potentially could serve as a biomarker for early breast cancer detection.

وصف الملف: image/pdf

العلاقة: https://dspace.library.uu.nl/handle/1874/338700Test

الإتاحة: https://dspace.library.uu.nl/handle/1874/338700Test

المؤلفون: Lo, Pang-Kuo, Lee, Ji Shin, Liang, Xiaohui, Sukumar, Saraswati

المساهمون: National Institutes of Health, Department of Defense

المصدر: Cellular Signalling ; volume 28, issue 10, page 1502-1519 ; ISSN 0898-6568

مصطلحات موضوعية: Cell Biology

الإتاحة: https://doi.org/10.1016/j.cellsig.2016.06.021Test
https://api.elsevier.com/content/article/PII:S0898656816301553?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0898656816301553?httpAccept=text/plainTest

المؤلفون: Bloushtain-Qimron, Noga, Yao, Jun, Snyder, Eric L., Shipitsin, Michail, Campbell, Lauren L., Mani, Sendurai A., Hu, Min, Chen, Haiyan, Ustyansky, Vadim, Antosiewicz, Jessica E., Argani, Pedram, Halushka, Marc K., Thomson, James A., Pharoah, Paul, Porgador, Angel, Sukumar, Saraswati, Parsons, Ramon, Richardson, Andrea L., Stampfer, Martha R., Gelman, Rebecca S., Nikolskaya, Tatiana, Nikolsky, Yuri, Polyak, Kornelia

المصدر: Proceedings of the National Academy of Sciences of the United States of America, 2008 Sep . 105(37), 14076-14081.

الوصول الحر: https://www.jstor.org/stable/25464178Test