Medicine and Health Sciences Commons^™

Integrated Proteotranscriptomics Of Breast Cancer Reveals Globally Increased Protein-Mrna Concordance Associated With Subtypes And Survival, Wei Tang, Ming Zhou, Tiffany H Dorsey, Darue A Prieto, Xin W Wang, Eytan Ruppin, Timothy Veenstra, Stefan Ambs

Pharmaceutical Sciences Faculty Publications

BACKGROUND: Transcriptome analysis of breast cancer discovered distinct disease subtypes of clinical significance. However, it remains a challenge to define disease biology solely based on gene expression because tumor biology is often the result of protein function. Here, we measured global proteome and transcriptome expression in human breast tumors and adjacent non-cancerous tissue and performed an integrated proteotranscriptomic analysis.

METHODS: We applied a quantitative liquid chromatography/mass spectrometry-based proteome analysis using an untargeted approach and analyzed protein extracts from 65 breast tumors and 53 adjacent non-cancerous tissues. Additional gene expression data from Affymetrix Gene Chip Human Gene ST Arrays were available …

Relation Of Serum Estrogen Metabolites With Terminal Duct Lobular Unit Involution Among Women Undergoing Diagnostic Image-Guided Breast Biopsy., Hannah Oh, Zeina G Khodr, Mark E Sherman, Maya Palakal, Ruth M Pfeiffer, Laura Linville, Berta M Geller, Pamela M Vacek, Donald L Weaver, Rachael E Chicoine, Roni T Falk, Hisani N Horne, Daphne Papathomas, Deesha A Patel, Jackie Xiang, Xia Xu, Timothy Veenstra, Stephen M Hewitt, John A Shepherd, Louise A Brinton, Jonine D Figueroa, Gretchen L Gierach

Pharmaceutical Sciences Faculty Publications

Higher levels of circulating estrogens and estrogen metabolites (EMs) have been associated with higher breast cancer risk. In breast tissues, reduced levels of terminal duct lobular unit (TDLU) involution, as reflected by higher numbers of TDLUs and acini per TDLU, have also been linked to elevated breast cancer risk. However, it is unknown whether reduced TDLU involution mediates the risk associated with circulating EMs. In a cross-sectional analysis of 94 premenopausal and 92 postmenopausal women referred for clinical breast biopsy at an academic facility in Vermont, we examined the associations of 15 EMs, quantified using liquid chromatography-tandem mass spectrometry, with …

Microfilariae Of Brugia Malayi Inhibit The Mtor Pathway And Induce Autophagy In Human Dendritic Cells, Prakash Babu Narasimhan, Sasisekhar Bennuru, Zhaojing Meng, Rachel N Cotton, Kathleen R Elliott, Sundar Ganesan, Renee Mcdonald-Fleming, Timothy Veenstra, Thomas B Nutman, Roshanak Tolouei Semnani

Pharmaceutical Sciences Faculty Publications

Immune modulation is a hallmark of patent filarial infection, including suppression of antigen-presenting cell function and downmodulation of filarial antigen-specific T cell responses. The mammalian target of rapamycin (mTOR) signaling pathway has been implicated in immune regulation, not only by suppressing T cell responses but also by regulating autophagy (through mTOR sensing amino acid availability). Global proteomic analysis (liquid chromatography-tandem mass spectrometry) of microfilaria (mf)-exposed monocyte-derived dendritic cells (DC) indicated that multiple components of the mTOR signaling pathway, including mTOR, eIF4A, and eIF4E, are downregulated by mf, suggesting that mf target this pathway for immune modulation in DC. Utilizing Western …