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 …

Estrogen Metabolites In Human Corpus Luteum Physiology: Differential Effects On Angiogenic Activity, Soledad Henríquez, Paulina Kohen, Xia Xu, Timothy Veenstra, Alex Muñoz, Wilder A Palomino, Jerome F Strauss, Luigi Devoto

Pharmaceutical Sciences Faculty Publications

OBJECTIVE: To determine tissue concentrations of E2, estrone, P, and estrogens metabolites (EMs) 2-methoxyestradiol, 2-methoxyestrone, 4-hydroxyestrone, and 16-ketoestradiol in corpus luteum (CL) of different ages, and after hCG administration; and to examine the effects of EMs on vascular endothelial growth factor (VEGF) secretion and angiogenic activity released by cultured luteinizing granulosa cells in the presence and absence of hCG.

DESIGN: Experimental study.

SETTING: University.

PATIENT(S): Thirty-two healthy women of reproductive age.

INTERVENTION(S): Corpus luteum was collected at the time of minilaparotomy for tubal sterilization, at varying stages of the luteal phase (LP). Late-LP CL was collected 24 hours after IM …

Health Literacy Influences Heart Failure Knowledge Attainment But Not Self-Efficacy For Self-Care Or Adherence To Self-Care Over Time, Aleda M.H. Chen, Karen S. Yehle, Nancy M. Albert, Kenneth F. Ferraro, Holly L. Mason, Matthew M. Murawski, Kimberly S. Plake

Pharmacy Practice Faculty Publications

Background. Inadequate health literacy may be a barrier to gaining knowledge about heart failure (HF) self-care expectations, strengthening self-efficacy for self-care behaviors, and adhering to self-care behaviors over time. Objective. To examine if health literacy is associated with HF knowledge, self-efficacy, and self-care adherence longitudinally. Methods. Prior to education, newly referred patients at three HF clinics (, age: years) completed assessments of health literacy, HF knowledge, self-efficacy, and adherence to self-care at baseline, 2, and 4 months. Repeated measures analysis of variance with Bonferroni-adjusted alpha levels was used to test longitudinal outcomes. Results. Health literacy was associated with HF knowledge …

A Humanized Pattern Of Aromatase Expression Is Associated With Mammary Hyperplasia In Mice, Hong Zhao, Elizabeth K. Pearson, David C. Brooks, John S. Coon, Dong Chen, Masashi Demura, Ming Zhang, Charles V. Clevenger, Xia Xu, Timothy D. Veenstra, Robert T. Chatterton, Francesco J. Demayo, Serdar E. Bulun

Pharmaceutical Sciences Faculty Publications

Aromatase is essential for estrogen production and is the target of aromatase inhibitors, the most effective endocrine treatment for postmenopausal breast cancer. Peripheral tissues in women, including the breast, express aromatase via alternative promoters. Female mice lack the promoters that drive aromatase expression in peripheral tissues; thus, we generated a transgenic humanized aromatase (Arom(hum)) mouse line containing a single copy of the human aromatase gene to study the link between aromatase expression in mammary adipose tissue and breast pathology. Arom(hum) mice expressed human aromatase, driven by the proximal human promoters II and I.3 and the distal promoter I.4, in breast …

Comparison Of Estrogens And Estrogen Metabolites In Human Breast Tissue And Urine, Emanuela Taioli, Annie Im, Xia Xu, Timothy D. Veenstra, Gretchen Ahrendt, Seymour Garte

Pharmaceutical Sciences Faculty Publications

BACKGROUND: An important aspect of the link between estrogen and breast cancer is whether urinary estrogen levels are representative of the intra-tissue levels of bioavailable estrogens.

METHODS: This study compares 15 estrogen and estrogen metabolite levels in breast tissue and urine of 9 women with primary breast cancer using a quantitative liquid chromatography-mass spectrometry method.

RESULTS: The average levels of estrogens (estrone, 17 beta-estradiol) were significantly higher in breast tissue than in urine. Both the 2 and the 16-hydroxylation pathways were less represented in breast tissue than urine; no components of the 4-hydroxypathway were detected in breast tissue, while 4-hydroxyestrone …