Browsing by Author "Backman, Vadim"

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    Author Correction: Lipid exposure activates gene expression changes associated with estrogen receptor negative breast cancer
    (Springer Nature, 2023-03-13) Yadav, Shivangi; Virk, Ranya; Chung, Carolina H.; Bustamante Eduardo, Mariana; VanDerway, David; Chen, Duojiao; Burdett, Kirsten; Gao, Hongyu; Zeng, Zexian; Ranjan, Manish; Cottone, Gannon; Xuei, Xiaoling; Chandrasekaran, Sriram; Backman, Vadim; Chatterton, Robert; Khan, Seema Ahsan; Clare, Susan E.; Medical and Molecular Genetics, School of Medicine
    Correction to: npj Breast Cancer 10.1038/s41523-022-00422-0, published online 04 May 2022 In this article, funding from the National Institutes of Health (award number R01CA228272) was inadvertently omitted. The original article has been corrected.
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    Lipid exposure activates gene expression changes associated with estrogen receptor negative breast cancer
    (Springer Nature, 2022-05-04) Yadav, Shivangi; Virk, Ranya; Chung, Carolina H.; Bustamante Eduardo, Mariana; VanDerway, David; Chen, Duojiao; Burdett, Kirsten; Gao, Hongyu; Zeng, Zexian; Ranjan, Manish; Cottone, Gannon; Xuei, Xiaoling; Chandrasekaran, Sriram; Backman, Vadim; Chatterton, Robert; Khan, Seema Ahsan; Clare, Susan E.; Medical and Molecular Genetics, School of Medicine
    Improved understanding of local breast biology that favors the development of estrogen receptor negative (ER-) breast cancer (BC) would foster better prevention strategies. We have previously shown that overexpression of specific lipid metabolism genes is associated with the development of ER- BC. We now report results of exposure of MCF-10A and MCF-12A cells, and mammary organoids to representative medium- and long-chain polyunsaturated fatty acids. This exposure caused a dynamic and profound change in gene expression, accompanied by changes in chromatin packing density, chromatin accessibility, and histone posttranslational modifications (PTMs). We identified 38 metabolic reactions that showed significantly increased activity, including reactions related to one-carbon metabolism. Among these reactions are those that produce S-adenosyl-L-methionine for histone PTMs. Utilizing both an in-vitro model and samples from women at high risk for ER- BC, we show that lipid exposure engenders gene expression, signaling pathway activation, and histone marks associated with the development of ER- BC.
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    Rectal Optical Markers for In-vivo Risk Stratification of Premalignant Colorectal Lesions.
    (AACR, 2015-10-01) Radosevich, Andrew J.; Mutyal, Nikhil N.; Eshein, Adam; Nguyen, The-Quyen; Gould, Bradley; Rogers, Jeremy D.; Goldberg, Michael J.; Bianchi, Laura K.; Yen, Eugene F.; Konda, Vani; Rex, Douglas K.; Van Dam, Jacques; Backman, Vadim; Roy, Hemant K.; Department of Medicine, IU School of Medicine
    Purpose: Colorectal cancer remains the second leading cause of cancer deaths in the U.S. despite being eminently preventable by colonoscopy via removal of premalignant adenomas. In order to more effectively reduce colorectal cancer mortality, improved screening paradigms are needed. Our group pioneered the use of low coherence enhanced backscattering (LEBS) spectroscopy to detect the presence of adenomas throughout the colon via optical interrogation of the rectal mucosa. In a previous ex-vivo biopsy study of 219 patients, LEBS demonstrated excellent diagnostic potential with 89.5% accuracy for advanced adenomas. The objective of the current cross-sectional study is to assess the viability of rectal LEBS in-vivo. Experimental Design: Measurements from 619 patients were taken using a minimally invasive 3.4 mm diameter LEBS probe introduced into the rectum via anoscope or direct insertion, requiring ~1 minute from probe insertion to withdrawal. The diagnostic LEBS marker was formed as a logistic regression of the optical reduced scattering coefficient μs∗ and mass density distribution factor D. Results: The rectal LEBS marker was significantly altered in patients harboring advanced adenomas and multiple non-advanced adenomas throughout the colon. Blinded and cross-validated test performance characteristics showed 88% sensitivity to advanced adenomas, 71% sensitivity to multiple non-advanced adenomas, and 72% specificity in the validation set. Conclusions: We demonstrate the viability of in-vivo LEBS measurement of histologically normal rectal mucosa to predict the presence of clinically relevant adenomas throughout the colon. The current work represents the next step in the development of rectal LEBS as a tool for colorectal cancer risk stratification.