Medicine and Health Sciences Commons^™

Androgen Receptor Signaling In Prostate Cancer And Therapeutic Strategies, Aasems Jacob, Rishi Raj, Derek B. Allison, Zin W. Myint

Markey Cancer Center Faculty Publications

Understanding of the molecular mechanisms of prostate cancer has led to development of therapeutic strategies targeting androgen receptor (AR). These androgen-receptor signaling inhibitors (ARSI) include androgen synthesis inhibitor-abiraterone and androgen receptor antagonists-enzalutamide, apalutamide, and darolutamide. Although these medications provide significant improvement in survival among men with prostate cancer, drug resistance develops in nearly all patients with time. This could be through androgen-dependent or androgen-independent mechanisms. Even weaker signals and non-canonical steroid ligands can activate AR in the presence of truncated AR-splice variants, AR overexpression, or activating mutations in AR. AR splice variant, AR-V7 is the most studied among these and …

Integrated Single-Cell Atlas Of Endothelial Cells Of The Human Lung, Jonas C Schupp, Taylor S Adams, Carlos Cosme, Micha Sam Brickman Raredon, Yifan Yuan, Norihito Omote, Sergio Poli, Maurizio Chioccioli, Kadi-Ann Rose, Edward P Manning, Maor Sauler, Giuseppe Deiuliis, Farida Ahangari, Nir Neumark, Arun C Habermann, Austin J Gutierrez, Linh T Bui, Robert Lafyatis, Richard W Pierce, Kerstin B Meyer, Martijn C Nawijn, Sarah A Teichmann, Nicholas E Banovich, Jonathan A Kropski, Laura E Niklason, Dana Pe'er, Xiting Yan, Robert J Homer, Ivan O Rosas, Naftali Kaminski

Journal Articles

BACKGROUND: Cellular diversity of the lung endothelium has not been systematically characterized in humans. We provide a reference atlas of human lung endothelial cells (ECs) to facilitate a better understanding of the phenotypic diversity and composition of cells comprising the lung endothelium.

METHODS: We reprocessed human control single-cell RNA sequencing (scRNAseq) data from 6 datasets. EC populations were characterized through iterative clustering with subsequent differential expression analysis. Marker genes were validated by fluorescent microscopy and in situ hybridization. scRNAseq of primary lung ECs cultured in vitro was performed. The signaling network between different lung cell types was studied. For cross-species …

Magnetic Resonance Biomarkers In Radiation Oncology: The Report Of Aapm Task Group 294, Kiaran P Mcgee, Ken-Pin Hwang, Daniel C Sullivan, John Kurhanewicz, Yanle Hu, Jihong Wang, Wen Li, Josef Debbins, Eric Paulson, Jeffrey R Olsen, Chia-Ho Hua, Lizette Warner, Daniel Ma, Eduardo Moros, Neelam Tyagi, Caroline Chung

Journal Articles

A magnetic resonance (MR) biologic marker (biomarker) is a measurable quantitative characteristic that is an indicator of normal biological and pathogenetic processes or a response to therapeutic intervention derived from the MR imaging process. There is significant potential for MR biomarkers to facilitate personalized approaches to cancer care through more precise disease targeting by quantifying normal versus pathologic tissue function as well as toxicity to both radiation and chemotherapy. Both of which have the potential to increase the therapeutic ratio and provide earlier, more accurate monitoring of treatment response. The ongoing integration of MR into routine clinical radiation therapy (RT) …

A Metabolomic Endotype Of Bioenergetic Dysfunction Predicts Mortality In Critically Ill Patients With Acute Respiratory Failure, Raymond J. Langley, Marie E. Migaud, Lori Flores, J. Will Thompson, Elizabeth A. Kean, Murphy M. Mostellar, Matthew Mowry, Patrick Luckett, Lina D. Purcell, James Lovato, Sheetal Gandotra, Ryan Benton, D. Clark Files, Kevin S. Harrod, Mark N. Gillespie, Peter E. Morris

Internal Medicine Faculty Publications

Acute respiratory failure (ARF) requiring mechanical ventilation, a complicating factor in sepsis and other disorders, is associated with high morbidity and mortality. Despite its severity and prevalence, treatment options are limited. In light of accumulating evidence that mitochondrial abnormalities are common in ARF, here we applied broad spectrum quantitative and semiquantitative metabolomic analyses of serum from ARF patients to detect bioenergetic dysfunction and determine its association with survival. Plasma samples from surviving and non-surviving patients (N = 15/group) were taken at day 1 and day 3 after admission to the medical intensive care unit and, in survivors, at hospital discharge. …

Predictive Factors For Success Of Awake Proning In Hypoxemic Respiratory Failure Secondary To Covid-19: A Retrospective Cohort Study, Sujith V Cherian, Chang Li, Brad Roche, Stephan A Reyes, Siddharth Karanth, Aditya P Lal, Gabriel M Aisenberg, Rosa M Estrada-Y-Martin

Journal Articles

BACKGROUND: Awake prone positioning has been recommended as an adjunctive measure in spontaneously breathing patients with hypoxemic respiratory failure during the COVID-19 pandemic. It remains uncertain as to how long this should be implemented, what variables to follow and who would be the ideal candidates for this adjunctive therapy.

METHODS: A retrospective chart review of patients admitted from April to August 2020 within our institution with multifocal pneumonia and hypoxemic respiratory failure secondary to COVID-19 who underwent awake-proning for at least 3 hours was conducted.

RESULTS: Improvement in respiratory parameters including ROX (SpO2/Fio2/ Respiratory Rate) indices and inflammatory markers within …

Real World Clinicopathologic Observations Of Patients With Metastatic Solid Tumors Receiving Immune Checkpoint Inhibitor Therapy: Analysis From Kentucky Cancer Registry, Aasems Jacob, Jianrong Wu, Jill M. Kolesar, Eric B. Durbin, Aju Mathew, Susanne Arnold, Aman Chauhan

Biostatistics Faculty Publications

The state of Kentucky has the highest cancer incidence and mortality in the United States. High‐risk populations such as this are often underrepresented in clinical trials. The study aims to do a comprehensive analysis of molecular landscape of metastatic cancers among these patients with detailed evaluation of factors affecting response and outcomes to immune checkpoint inhibitor (ICI) therapy. We performed a retrospective analysis of metastatic solid tumor patients who received ICI and underwent molecular profiling at our institution.

Sixty nine patients with metastatic solid tumors who received ICI were included in the study. Prevalence of smoking and secondhand tobacco exposure …