Open Access. Powered by Scholars. Published by Universities.®

Medical Specialties Commons™

Open Access. Powered by Scholars. Published by Universities.®

Oncology

Institution
Keyword
Publication Year
Publication
Publication Type
File Type

Articles 8071 - 8100 of 14308

Full-Text Articles in Medical Specialties

Integrative Metabolomics And Transcriptomics Analysis Reveals Novel Therapeutic Vulnerabilities In Lung Cancer, Jose Thaiparambil, Jianrong Dong, Sandra L Grimm, Dimuthu Perera, Chandra Shekar R Ambati, Vasanta Putluri, Matthew J Robertson, Tajhal D Patel, Brandon Mistretta, Preethi H Gunaratne, Min P Kim, Jason T Yustein, Nagireddy Putluri, Cristian Coarfa, Randa El-Zein Jan 2023

Integrative Metabolomics And Transcriptomics Analysis Reveals Novel Therapeutic Vulnerabilities In Lung Cancer, Jose Thaiparambil, Jianrong Dong, Sandra L Grimm, Dimuthu Perera, Chandra Shekar R Ambati, Vasanta Putluri, Matthew J Robertson, Tajhal D Patel, Brandon Mistretta, Preethi H Gunaratne, Min P Kim, Jason T Yustein, Nagireddy Putluri, Cristian Coarfa, Randa El-Zein

Faculty, Staff and Students Publications

BACKGROUND: Non-small cell lung cancer (NSCLC) comprises the majority (~85%) of all lung tumors, with lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) being the most frequently diagnosed histological subtypes. Multi-modal omics profiling has been carried out in NSCLC, but no studies have yet reported a unique metabolite-related gene signature and altered metabolic pathways associated with LUAD and LUSC.

METHODS: We integrated transcriptomics and metabolomics to analyze 30 human lung tumors and adjacent noncancerous tissues. Differential co-expression was used to identify modules of metabolites that were altered between normal and tumor.

RESULTS: We identified unique metabolite-related gene signatures specific for …


Lox Upregulates Fak Phosphorylation To Promote Metastasis In Osteosarcoma, Xiang Chen, Margaret Clement, M John Hicks, Poonam Sarkar, M Waleed Gaber, Tsz-Kwong Man Jan 2023

Lox Upregulates Fak Phosphorylation To Promote Metastasis In Osteosarcoma, Xiang Chen, Margaret Clement, M John Hicks, Poonam Sarkar, M Waleed Gaber, Tsz-Kwong Man

Faculty, Staff and Students Publications

Osteosarcoma is a malignant bone tumor that commonly occurs in the pediatric population. Despite the use of chemotherapy and surgery, metastasis remains to be the leading cause of death in patients with osteosarcoma. We have previously reported that cytoplasmic mislocalization of p27 is associated with a poor outcome in osteosarcoma. In this study, we further show that lysyl oxidase (LOX) expression was associated with p27 mislocalization. LOX is an enigmatic molecule that acts as a tumor suppressor or a metastatic promoter; however, its role in osteosarcoma is still unclear. Hence, we performed both


Pre-Treatment Inflamed Tumor Immune Microenvironment Is Associated With Folfirinox Response In Pancreatic Cancer, Zachary Gao, Sung Wook Kang, Derek Erstad, Joseph Azar, George Van Buren, William Fisher, Zequn Sun, Mark P Rubinstein, Hyun-Sung Lee, E Ramsay Camp Jan 2023

Pre-Treatment Inflamed Tumor Immune Microenvironment Is Associated With Folfirinox Response In Pancreatic Cancer, Zachary Gao, Sung Wook Kang, Derek Erstad, Joseph Azar, George Van Buren, William Fisher, Zequn Sun, Mark P Rubinstein, Hyun-Sung Lee, E Ramsay Camp

Faculty, Staff and Students Publications

INTRODUCTION: Pancreatic adenocarcinoma (PDAC) is an aggressive tumor with limited response to both chemotherapy and immunotherapy. Pre-treatment tumor features within the tumor immune microenvironment (TiME) may influence treatment response. We hypothesized that the pre-treatment TiME composition differs between metastatic and primary lesions and would be associated with response to modified FOLFIRINOX (mFFX) or gemcitabine-based (Gem-based) therapy.

METHODS: Using RNAseq data from a cohort of treatment-naïve, advanced PDAC patients in the COMPASS trial, differential gene expression analysis of key immunomodulatory genes in were analyzed based on multiple parameters including tumor site, response to mFFX, and response to Gem-based treatment. The relative …


Systemic Treatment Of Advanced And Metastatic Urothelial Cancer: The Landscape In Australia, Howard Gurney, Timothy D. Clay, Niara Oliveira, Shirley Wong, Ben Tran, Carole Harris Jan 2023

Systemic Treatment Of Advanced And Metastatic Urothelial Cancer: The Landscape In Australia, Howard Gurney, Timothy D. Clay, Niara Oliveira, Shirley Wong, Ben Tran, Carole Harris

Research outputs 2022 to 2026

The 5-year survival rate of metastatic urothelial carcinoma (mUC) is estimated to be as low as 5%. Currently, systemic platinum-based chemotherapy followed by avelumab maintenance therapy is the only first-line treatment for mUC that has an overall survival benefit. Cisplatin-based chemotherapy (usually in combination with gemcitabine) is the preferred treatment but carboplatin is substituted where contraindications to cisplatin exist. Treatment with immune checkpoint inhibitors, antibody-drug conjugates, and kinase inhibitors has not yet demonstrated superiority to chemotherapy as first-line therapy and remains investigational in this setting. A recent media release indicates that chemotherapy plus nivolumab gives an OS advantage as first-line …


Women In Lymphoma: A 4-Year Journey In Promoting Gender Equity, Judith Trotman, Ann Lacasce, Wendy Osborne, Anna Steiner, Eliza Hawkes, Carla Casulo, Florence Broussais, Kate Cwynarski, Paola Ghione, Justine Kahn, Sharyn Kurtz, Kim Linton, Carolina Mahuad, Monique Minnema, Loretta Nastoupil, Wendy Osborne, Astrid Pavolvsky, Michelle Poon, Clementine Sarkozy, Laurie Sehn, Soni Smith, Anna Sureda, Carrie Thompson, Judith Trotman, Julie M. Vose Jan 2023

Women In Lymphoma: A 4-Year Journey In Promoting Gender Equity, Judith Trotman, Ann Lacasce, Wendy Osborne, Anna Steiner, Eliza Hawkes, Carla Casulo, Florence Broussais, Kate Cwynarski, Paola Ghione, Justine Kahn, Sharyn Kurtz, Kim Linton, Carolina Mahuad, Monique Minnema, Loretta Nastoupil, Wendy Osborne, Astrid Pavolvsky, Michelle Poon, Clementine Sarkozy, Laurie Sehn, Soni Smith, Anna Sureda, Carrie Thompson, Judith Trotman, Julie M. Vose

Journal Articles: Oncology and Hematology

No abstract provided.


The Salento Prognostic Model For Limited-Stage Peripheral T-Cell Lymphoma From The International T-Cell Project Network, Greg Hapgood, Monica Civallero, Yana Stepanishyna, Julie M. Vose, Monica Elena Cabrera, Ranjana H Advani, Stefano A. Pileri, Martina Manni, Steven M. Horwitz, Francine M. Foss, Felicitas Hitz, John Radford, Ivan Dlouhy, Carlos Chiattone, Won Seog Kim, Tetiana Skrypets, Arnon Nagler, Judith Trotman, Stefano Luminari, Massimo Federico Jan 2023

The Salento Prognostic Model For Limited-Stage Peripheral T-Cell Lymphoma From The International T-Cell Project Network, Greg Hapgood, Monica Civallero, Yana Stepanishyna, Julie M. Vose, Monica Elena Cabrera, Ranjana H Advani, Stefano A. Pileri, Martina Manni, Steven M. Horwitz, Francine M. Foss, Felicitas Hitz, John Radford, Ivan Dlouhy, Carlos Chiattone, Won Seog Kim, Tetiana Skrypets, Arnon Nagler, Judith Trotman, Stefano Luminari, Massimo Federico

Journal Articles: Oncology and Hematology

The natural history of limited-stage peripheral T-cell lymphomas (PTCLs) remains poorly defined. We investigated outcomes and prognostic variables in patients registered in the T-Cell Project (TCP) (#NCT01142674) to develop a model to predict overall survival (OS) for the common nodal PTCL subtypes (PTCL-NOS, AITL, ALCL). The model was validated in an independent data set from Australian and Brazilian registries. 211 patients registered in the TCP between 2006-2018 were studied. The median age was 59 years (range 18-88) and median follow-up was 49 months. One hundred twenty-seven patients (78%) received anthracycline-based regimens, 5 patients (3%) radiotherapy alone (RT), 24 patients (15%) …


Metabolic Reprogramming Driven By Ezh2 Inhibition Depends On Cell–Matrix Interactions, Teresa W-M Fan, Jahid M. M. Islam, Richard M. Higashi, Penghui Lin, Christine F. Brainson, Andrew N. Lane Jan 2023

Metabolic Reprogramming Driven By Ezh2 Inhibition Depends On Cell–Matrix Interactions, Teresa W-M Fan, Jahid M. M. Islam, Richard M. Higashi, Penghui Lin, Christine F. Brainson, Andrew N. Lane

Markey Cancer Center Faculty Publications

EZH2 (Enhancer of Zeste Homolog 2), a subunit of Poly- comb Repressive Complex 2 (PRC2), catalyzes the trimethyla- tion of histone H3 at lysine 27 (H3K27me3), which represses expression of genes. It also has PRC2-independent functions, including transcriptional coactivation of oncogenes, and is frequently overexpressed in lung cancers. Clinically, EZH2 in- hibition can be achieved with the FDA-approved drug EPZ- 6438 (tazemetostat). To realize the full potential of EZH2 blockade, it is critical to understand how cell-cell/cell-matrix interactions present in 3D tissue and cell culture systems in- fluences this blockade in terms of growth-related metabolic functions. Here, we show that …


A Monoadduct Generating Ru(Ii) Complex Induces Ribosome Biogenesis Stress And Is A Molecular Mimic Of Phenanthriplatin, Richard Joseph Mitchell, Sarah M. Kriger, Alexander D. Fenton, Dmytro Havrylyuk, Ankit Pandeya, Yang Sun, Tami Smith, Jason E. Derouchey, David K. Heidary, Edith C. Glazer Jan 2023

A Monoadduct Generating Ru(Ii) Complex Induces Ribosome Biogenesis Stress And Is A Molecular Mimic Of Phenanthriplatin, Richard Joseph Mitchell, Sarah M. Kriger, Alexander D. Fenton, Dmytro Havrylyuk, Ankit Pandeya, Yang Sun, Tami Smith, Jason E. Derouchey, David K. Heidary, Edith C. Glazer

Markey Cancer Center Faculty Publications

Ruthenium complexes are often investigated as potential replacements for platinum-based chemotherapeutics in hopes of identifying systems with improved tolerability in vivo and reduced susceptibility to cellular resistance mechanisms. Inspired by phenanthriplatin, a non-traditional platinum agent that contains only one labile ligand, monofunctional ruthenium polypyridyl agents have been developed, but until now, few demonstrated promising anticancer activity. Here we introduce a potent new scaffold, based on [Ru(tpy)(dip)Cl]Cl (tpy = 2,20:60,200-terpyridine and dip = 4,7-diphenyl-1,10-phenanthroline) in pursuit of effective Ru(II )-based monofunctional agents. Notably, the extension of the terpyridine at the 40 position with an aromatic ring resulted in a molecule that …


Assessment Of Opioid-Induced Immunomodulation In Experimental And Clinical Sepsis, Brittany Dawn Bissell, Jamie L. Sturgill, Maria E. C. Bruno, Erick D. Lewis, Marlene E. Starr Jan 2023

Assessment Of Opioid-Induced Immunomodulation In Experimental And Clinical Sepsis, Brittany Dawn Bissell, Jamie L. Sturgill, Maria E. C. Bruno, Erick D. Lewis, Marlene E. Starr

Markey Cancer Center Faculty Publications

CONTEXT: Opioids remain a standard supportive therapy in patients admitted to the ICU with sepsis. However, as preclinical models indicate an association between opioid exposure and immunosuppression, the use of this class of drugs warrants investigation. The objective of this study was to investigate whether opioid exposure causes immunosuppression in patients with sepsis, and to use a murine sepsis model to determine the effects of opioid exposure on secondary infection.

HYPOTHESIS: We hypothesized opioid exposure would be associated with immunosuppression in patients with sepsis and secondary infection in a murine sepsis model.

METHODS AND MODELS: This was a two-phase preclinical …


Bilirubin Levels Are Negatively Correlated With Adiposity In Obese Men And Women, And Its Catabolized Product, Urobilin, Is Positively Associated With Insulin Resistance, Zachary A. Kipp, Mei Xu, Evelyn A. Bates, Wang-Hsin Lee, Philip A. Kern, Terry D. Hinds Jr. Jan 2023

Bilirubin Levels Are Negatively Correlated With Adiposity In Obese Men And Women, And Its Catabolized Product, Urobilin, Is Positively Associated With Insulin Resistance, Zachary A. Kipp, Mei Xu, Evelyn A. Bates, Wang-Hsin Lee, Philip A. Kern, Terry D. Hinds Jr.

Markey Cancer Center Faculty Publications

Bilirubin levels in obese humans and rodents have been shown to be lower than in their lean counterparts. Some studies have proposed that the glucuronyl UGT1A1 enzyme that clears bilirubin from the blood increases in the liver with obesity. UGT1A1 clearance of bilirubin allows more conjugated bilirubin to enter the intestine, where it is catabolized into urobilin, which can be then absorbed via the hepatic portal vein. We hypothesized that when bilirubin levels are decreased, the urobilin increases in the plasma of obese humans, as compared to lean humans. To test this, we measured plasma levels of bilirubin and urobilin, …


Computational Investigation Of A Series Of Small Molecules As Potential Compounds For Lysyl Hydroxylase-2 (Lh2) Inhibition, Yazdan Maghsoud, Erik Antonio Vázquez-Montelongo, Xudong Yang, Chengwen Liu, Zhifeng Jing, Juhoon Lee, Matthew Harger, Ally K. Smith, Miguel Espinoza, Hou-Fu Guo, Jonathan M. Kurie, Kevin N. Dalby, Pengyu Ren, G. Andrés Cisneros Jan 2023

Computational Investigation Of A Series Of Small Molecules As Potential Compounds For Lysyl Hydroxylase-2 (Lh2) Inhibition, Yazdan Maghsoud, Erik Antonio Vázquez-Montelongo, Xudong Yang, Chengwen Liu, Zhifeng Jing, Juhoon Lee, Matthew Harger, Ally K. Smith, Miguel Espinoza, Hou-Fu Guo, Jonathan M. Kurie, Kevin N. Dalby, Pengyu Ren, G. Andrés Cisneros

Markey Cancer Center Faculty Publications

The catalytic function of lysyl hydroxylase-2 (LH2), a member of the Fe(II)/αKG-dependent oxygenase superfamily, is to catalyze the hydroxylation of lysine to hydroxylysine in collagen, resulting in stable hydroxylysine aldehyde-derived collagen cross- links (HLCCs). Reports show that high amounts of LH2 lead to the accumulation of HLCCs, causing fibrosis and specific types of cancer metastasis. Some members of the Fe(II)/αKG-dependent family have also been reported to have intramolecular O2 tunnels, which aid in transporting one of the required cosubstrates into the active site. While LH2 can be a promising target to combat these diseases, efficacious inhibitors are still lacking. We …


Dysregulated Polycomb Repressive Complex 2 Contributes To Chronic Obstructive Pulmonary Disease By Rewiring Stem Cell Fate, Aria Byrd, Xufeng Qu, Alexsandr Lukyanchuk, Jinpeng Liu, Fan Chen, Kassandra J. Naughton, Tanner Ducote, Xiulong Song, Hannah Bowman, Yanming Zhao, Abigail R Edgin, Chi Wang, Jinze Liu, Christine Fillmore Brainson Jan 2023

Dysregulated Polycomb Repressive Complex 2 Contributes To Chronic Obstructive Pulmonary Disease By Rewiring Stem Cell Fate, Aria Byrd, Xufeng Qu, Alexsandr Lukyanchuk, Jinpeng Liu, Fan Chen, Kassandra J. Naughton, Tanner Ducote, Xiulong Song, Hannah Bowman, Yanming Zhao, Abigail R Edgin, Chi Wang, Jinze Liu, Christine Fillmore Brainson

Markey Cancer Center Faculty Publications

Aberrant lung cell differentiation is a hallmark of many lung diseases including chronic obstructive pulmonary disease (COPD). The EZH2-containing Polycomb Repressive Complex 2 (PRC2) regulates embryonic lung stem cell fate, but its role in adult lung is obscure. Histological analysis of patient tissues revealed that loss of PRC2 activity was correlated with aberrant bronchiolar cell differentiation in COPD lung. Histological and single-cell RNA-sequencing analyses showed that loss of EZH2 in mouse lung organoids led to lowered self- renewal capability, increased squamous morphological development, and marked shifts in progenitor cell populations. Evaluation of in vivo models revealed that heterozygosity of Ezh2 …


Extracellular Vesicle Distribution And Localization In Skeletal Muscle At Rest And Following Disuse Atrophy, Ahmed Ismaeel, Douglas W. Van Pelt, Zachary Hettinger, Xu Fu, Christopher I. Richards, Timothy A. Butterfield, Jonathan J. Petrocelli, Ivan J. Vechetti Jr., Amy L. Confides, Micah J. Drummond, Esther E. Dupont-Versteegden Jan 2023

Extracellular Vesicle Distribution And Localization In Skeletal Muscle At Rest And Following Disuse Atrophy, Ahmed Ismaeel, Douglas W. Van Pelt, Zachary Hettinger, Xu Fu, Christopher I. Richards, Timothy A. Butterfield, Jonathan J. Petrocelli, Ivan J. Vechetti Jr., Amy L. Confides, Micah J. Drummond, Esther E. Dupont-Versteegden

Markey Cancer Center Faculty Publications

Background Skeletal muscle (SkM) is a large, secretory organ that produces and releases myokines that can have autocrine, paracrine, and endocrine effects. Whether extracellular vesicles (EVs) also play a role in the SkM adaptive response and ability to communicate with other tissues is not well understood. The purpose of this study was to investigate EV biogenesis factors, marker expression, and localization across cell types in the skeletal muscle. We also aimed to investigate whether EV concentrations are altered by disuse atrophy.

Methods To identify the potential markers of SkM‑derived EVs, EVs were isolated from rat serum using density gradient ultracentrifugation, …


Glycolytic Regulation Of Intestinal Stem Cell Self-Renewal And Differentiation, Chang Li, Yuning Zhou, Ruozheng Wei, Dana L. Napier, Tomoko Sengoku, Michael Alstott, Jinpeng Liu, Chi Wang, Yekaterina Y. Zaytseva, Heidi L. Weiss, Qingding Wang, B. Mark Evers Jan 2023

Glycolytic Regulation Of Intestinal Stem Cell Self-Renewal And Differentiation, Chang Li, Yuning Zhou, Ruozheng Wei, Dana L. Napier, Tomoko Sengoku, Michael Alstott, Jinpeng Liu, Chi Wang, Yekaterina Y. Zaytseva, Heidi L. Weiss, Qingding Wang, B. Mark Evers

Markey Cancer Center Faculty Publications

BACKGROUND AND AIMS: The intestinal mucosa undergoes a continual process of proliferation, differentiation, and apoptosis. An imbalance in this highly regimented process within the intestinal crypts is associated with several intestinal pathologies. Although metabolic changes are known to play a pivotal role in cell proliferation and differentiation, how glycolysis contributes to intestinal epithelial homeostasis remains to be defined.

METHODS: Small intestines were harvested from mice with specific hexokinase 2 (HK2) deletion in the intestinal epithelium or LGR5þ stem cells. Glycolysis was measured using the Seahorse XFe96 analyzer. Expression of phospho-p38 mitogen- activated protein kinase, the transcription factor atonal homolog 1, …


Impact Of The Affordable Care Act On Providing Equitable Healthcare Access For Ibd In The Kentucky Appalachian Region, Jennifer T. Castle, Brittany Levy, Anthony A. Mangino, Hannah G. Mcdonald, Erin E. Mcatee, Jitesh A. Patel, B. Mark Evers, Avinash S. Bhakta Jan 2023

Impact Of The Affordable Care Act On Providing Equitable Healthcare Access For Ibd In The Kentucky Appalachian Region, Jennifer T. Castle, Brittany Levy, Anthony A. Mangino, Hannah G. Mcdonald, Erin E. Mcatee, Jitesh A. Patel, B. Mark Evers, Avinash S. Bhakta

Markey Cancer Center Faculty Publications

BACKGROUND: Medicaid expansion improved insurance coverage for patients with chronic conditions and low income. The effect of Medicaid expansion on patients with IBD from high-poverty communities is unknown.

OBJECTIVE: This study aimed to evaluate the impact of Medicaid expansion in Kentucky on care for patients with IBD from the Eastern Kentucky Appalachian community, a historically impoverished area.

DESIGN: This study was a retrospective, descriptive, and ecological study.

SETTINGS: This study was conducted in Kentucky using the Hospital Inpatient Discharge and Outpatient Services Database.

PATIENTS: All encounters for IBD care for 2009–2020 for patients from the Eastern Kentucky Appalachian region were …


Long-Term Kidney Function Recovery And Mortality After Covid-19-Associated Acute Kidney Injury: An International Multi-Centre Observational Cohort Study, Byom W. L. Tan, Bryce W. Q. Tan, Kee Yuan Ngiam, The Consortium For Clinical Characterization Of Covid-19 By Ehr (4ce) Jan 2023

Long-Term Kidney Function Recovery And Mortality After Covid-19-Associated Acute Kidney Injury: An International Multi-Centre Observational Cohort Study, Byom W. L. Tan, Bryce W. Q. Tan, Kee Yuan Ngiam, The Consortium For Clinical Characterization Of Covid-19 By Ehr (4ce)

Markey Cancer Center Faculty Publications

Background While acute kidney injury (AKI) is a common complication in COVID-19, data on post-AKI kidney function recovery and the clinical factors associated with poor kidney function recovery is lacking.

Methods A retrospective multi-centre observational cohort study comprising 12,891 hospitalized patients aged 18 years or older with a diagnosis of SARS-CoV-2 infection confirmed by polymerase chain reaction from 1 January 2020 to 10 September 2020, and with at least one serum creatinine value 1–365 days prior to admission. Mortality and serum creatinine values were obtained up to 10 September 2021.

Findings Advanced age (HR 2.77, 95%CI 2.53–3.04, p < 0.0001), severe COVID-19 (HR 2.91, 95%CI 2.03–4.17, p < 0.0001), severe AKI (KDIGO stage 3: HR 4.22, 95%CI 3.55–5.00, p < 0.0001), and ischemic heart disease (HR 1.26, 95%CI 1.14–1.39, p < 0.0001) were associated with worse mortality outcomes. AKI severity (KDIGO stage 3: HR 0.41, 95%CI 0.37–0.46, p < 0.0001) was associated with worse kidney function recovery, whereas remdesivir use (HR 1.34, 95%CI 1.17–1.54, p < 0.0001) was associated with better kidney function recovery. In a subset of patients without chronic kidney disease, advanced age (HR 1.38, 95%CI 1.20–1.58, p < 0.0001), male sex (HR 1.67, 95%CI 1.45–1.93, p < 0.0001), severe AKI (KDIGO stage 3: HR 11.68, 95%CI 9.80–13.91, p < 0.0001), and hypertension (HR 1.22, 95%CI 1.10–1.36, p = 0.0002) were associated with post-AKI kidney function impairment. Furthermore, patients with COVID-19-associated AKI had significant and persistent elevations of baseline serum creatinine 125% or more at 180 days (RR 1.49, 95%CI 1.32–1.67) and 365 days (RR 1.54, 95%CI 1.21–1.96) compared to COVID-19 patients with no AKI.

Interpretation COVID-19-associated …


Polycomb Deficiency Drives A Foxp2-High Aggressive State Targetable By Epigenetic Inhibitors, Fan Chen, Aria Byrd, Jinpeng Liu, Robert M. Flight, Tanner Ducote, Kassandra J. Naughton, Xiulong Song, Abigail R Edgin, Alexsandr Lukyanchuk, Danielle T. Dixon, Christian M. Gosser, Dave-Preston Esoe, Rani Jayswal, Stuart H. Orkin, Hunter N. B. Moseley, Chi Wang, Christine Fillmore Brainson Jan 2023

Polycomb Deficiency Drives A Foxp2-High Aggressive State Targetable By Epigenetic Inhibitors, Fan Chen, Aria Byrd, Jinpeng Liu, Robert M. Flight, Tanner Ducote, Kassandra J. Naughton, Xiulong Song, Abigail R Edgin, Alexsandr Lukyanchuk, Danielle T. Dixon, Christian M. Gosser, Dave-Preston Esoe, Rani Jayswal, Stuart H. Orkin, Hunter N. B. Moseley, Chi Wang, Christine Fillmore Brainson

Markey Cancer Center Faculty Publications

Inhibitors of the Polycomb Repressive Complex 2 (PRC2) histone methyltransferase EZH2 are approved for certain cancers, but realizing their wider utility relies upon understanding PRC2 biology in each cancer system. Using a genetic model to delete Ezh2 in KRAS-driven lung adenocarcinomas, we observed that Ezh2 haplo-insufficient tumors were less lethal and lower grade than Ezh2 fully-insufficient tumors, which were poorly differentiated and metastatic. Using three-dimensional cultures and in vivo experiments, we determined that EZH2-deficient tumors were vulnerable to H3K27 demethylase or BET inhibitors. PRC2 loss/inhibition led to de-repression of FOXP2, a transcription factor that promotes migration and stemness, and FOXP2 …


Suppressing Hepatic Ugt1a1 Increases Plasma Bilirubin, Lowers Plasma Urobilin, Reorganizes Kinase Signaling Pathways And Lipid Species And Improves Fatty Liver Disease, Evelyn A. Bates, Zachary A. Kipp, Genesee J. Martinez, Olufunto O. Badmus, Mangala M. Soundarapandian, Donald Foster, Mei Xu, Justin F. Creeden, Jennifer R. Greer, Andrew J. Morris, David E. Stec, Terry D. Hinds Jr. Jan 2023

Suppressing Hepatic Ugt1a1 Increases Plasma Bilirubin, Lowers Plasma Urobilin, Reorganizes Kinase Signaling Pathways And Lipid Species And Improves Fatty Liver Disease, Evelyn A. Bates, Zachary A. Kipp, Genesee J. Martinez, Olufunto O. Badmus, Mangala M. Soundarapandian, Donald Foster, Mei Xu, Justin F. Creeden, Jennifer R. Greer, Andrew J. Morris, David E. Stec, Terry D. Hinds Jr.

Markey Cancer Center Faculty Publications

Several population studies have observed lower serum bilirubin levels in patients with non-alcoholic fatty liver disease (NAFLD). Yet, treatments to target this metabolic phenotype have not been explored. Therefore, we designed an N-Acetylgalactosamine (GalNAc) labeled RNAi to target the enzyme that clears bilirubin from the blood, the UGT1A1 glucuronyl enzyme (GNUR). In this study, male C57BL/6J mice were fed a high-fat diet (HFD, 60%) for 30 weeks to induce NAFLD and were treated subcutaneously with GNUR or sham (CTRL) once weekly for six weeks while continuing the HFD. The results show that GNUR treatments significantly raised plasma bilirubin levels and …


Impact Of The Appalachian Career Training In Oncology (Action) Program On Undergraduate Participants, Carol Hanley, Lauren Hudson, Chris Prichard, Nathan L. Vanderford Jan 2023

Impact Of The Appalachian Career Training In Oncology (Action) Program On Undergraduate Participants, Carol Hanley, Lauren Hudson, Chris Prichard, Nathan L. Vanderford

Markey Cancer Center Faculty Publications

Kentucky ranks first in the nation in cancer incidence and mortality. The Appalachian region of the state experiences the highest cancer disparities due to inequities in many social determinants of health. As a strategy for addressing cancer and education disparities in the region, the Appalachian Career Training in Oncology (ACTION) Program at the University of Kentucky Markey Cancer Center engaged 16 Appalachian-native undergraduate student participants annually in cancer-related activities. Students were recruited on an annual basis for the 2-year ACTION program. Entry, mid-point, and exit surveys were administered to participants. Classical test theory and exploratory factor analysis were used to …


A Qualitative Study Of Participant Perceptions Of A Cancer Research Education Program, Olivia Allran, Nathan L. Vanderford Jan 2023

A Qualitative Study Of Participant Perceptions Of A Cancer Research Education Program, Olivia Allran, Nathan L. Vanderford

Markey Cancer Center Faculty Publications

Kentucky ranks first in the nation in cancer incidence and mortality rates, with the greatest burden of disease being in the Appalachian region. The cancer disparities in the Appalachian region of the state are tied to high poverty rates, low education attainment, low health care access, and high rates of poor health behaviors, such as tobacco use. The University of Kentucky (UK) Markey Cancer Center (MCC) developed the Appalachian Career Training in Oncology (ACTION) program to address the cancer and education disparities in the region. ACTION is a two-year program that focuses on cancer education and training for high school …


The Link Between Intracellular Calcium Signaling And Exosomal Pd-L1 In Cancer Progression And Immunotherapy, Rakibul Alam, Mizanur Rahman, Zhiguo Li Jan 2023

The Link Between Intracellular Calcium Signaling And Exosomal Pd-L1 In Cancer Progression And Immunotherapy, Rakibul Alam, Mizanur Rahman, Zhiguo Li

Markey Cancer Center Faculty Publications

Exosomes are small membrane vesicles containing microRNA, RNA, DNA fragments, and proteins that are transferred from donor cells to recipient cells. Tumor cells release exo- somes to reprogram the factors associated with the tumor microenvironment (TME) causing tu- mor metastasis and immune escape. Emerging evidence revealed that cancer cell-derived exosomes carry immune inhibitory molecule program death ligand 1 (PD-L1) that binds with re- ceptor program death protein 1 (PD-1) and promote tumor progression by escaping immune response. Currently, some FDA-approved monoclonal antibodies are clinically used for cancer treatment by blocking PD-1/PD-L1 interaction. Despite notable treatment outcomes, some pa- tients show …


Xylazine Suppresses Fentanyl Consumption During Self-Administration And Induces A Unique Sex-Specific Withdrawal Syndrome That Is Not Altered By Naloxone In Rats, Shailesh N. Khatri, Safiyah M. Sadek, Percell T. Kendrick, Emma O. Bondy, Mei Hong, Sally Pauss, Dan Luo, Thomas E. Prisinzano, Kelly E. Dunn, Julie A. Marusich, Joshua S. Beckmann, Terry D. Hinds Jr., Cassandra D. Gipson Jan 2023

Xylazine Suppresses Fentanyl Consumption During Self-Administration And Induces A Unique Sex-Specific Withdrawal Syndrome That Is Not Altered By Naloxone In Rats, Shailesh N. Khatri, Safiyah M. Sadek, Percell T. Kendrick, Emma O. Bondy, Mei Hong, Sally Pauss, Dan Luo, Thomas E. Prisinzano, Kelly E. Dunn, Julie A. Marusich, Joshua S. Beckmann, Terry D. Hinds Jr., Cassandra D. Gipson

Markey Cancer Center Faculty Publications

Prescription and illicit opioid use are a public health crisis, with the landscape shifting to fentanyl use. Since fentanyl is 100-fold more potent than morphine, its use is associated with a higher risk of fatal overdose that can be remediated through naloxone (Narcan) administration. However, recent reports indicate that xylazine, an anesthetic, is increasingly detected in accidental fentanyl overdose deaths. Anecdotal reports suggest that xylazine may prolong the fentanyl “high,” alter the onset of fentanyl withdrawal, and increase resistance to naloxone-induced reversal of overdose. To date, no preclinical studies have evaluated the impacts of xylazine on fentanyl self-administration (SA; 2.5 …


A Nursing Staff Education Module On Survivorship Care Plans In Primary Care, Janette Francis Jan 2023

A Nursing Staff Education Module On Survivorship Care Plans In Primary Care, Janette Francis

Walden Dissertations and Doctoral Studies

Survivorship care plans (SCPs) bridge the gap in the transition of care from oncology to primary care providers (PCPs) for breast cancer survivors. Despite strong recommendations for SCPs, their use remains limited. Guided by Knowles’ adult learning theory, the project focused on, first, determining whether a predeveloped staff education activity was valid using the Lynn model criteria for validation. Second, if in a rural clinic where SCP were not consistently used providers, nurses, and staff knowledge regarding the importance of SCP would increase following an educational program. An expert panel of 5 educational experts validated the educational module for appropriateness …


Factors Impacting College Students’ Receipt Of Human Papillomavirus Vaccination, Joy Yvette Payne Jan 2023

Factors Impacting College Students’ Receipt Of Human Papillomavirus Vaccination, Joy Yvette Payne

Walden Dissertations and Doctoral Studies

Less than half of U. S. students entering college have had a human papillomavirus (HPV) vaccination, placing them at risk for HPV-related cancers. This study’s purpose was to identify predictors of HPV vaccination initiation in college students. Andersen’s behavioral model of health services use was used to examine the differences in predisposing, enabling, and need factors in U.S. college students ages 18–26 years who received an initial HPV vaccination in college compared to those who never received an HPV vaccination. The study was a quantitative, cross-sectional survey design using multivariable logistic regression for data analyses. Data were collected through an …


Oncology Nurses, Compassion Fatigue And General Health: A Mixed-Methods Study, Michelle Rampersad Jan 2023

Oncology Nurses, Compassion Fatigue And General Health: A Mixed-Methods Study, Michelle Rampersad

Walden Dissertations and Doctoral Studies

Current literature on compassion fatigue is expansive, but there is a lack on the relationship between compassion fatigue and general health complaints in oncology nurses; how they perceive compassion fatigue and its relation to their general health. Using Pender’s health promotion model, this mixed methods study addressed how oncology nurses perceive compassion fatigue and whether a correlation exists between compassion fatigue and general health complaints. Data were collected from a sample of 55 oncology nurses through two separate Survey Monkey links. All 55 participants completed quantitative data points including a demographic questionnaire, the Professional Quality of Life 5 tool, and …


A Lifestyle Management Coaching Intervention For Fear Of Cancer Recurrence In Young Breast Cancer Survivors, Lisa R. Murphy Jan 2023

A Lifestyle Management Coaching Intervention For Fear Of Cancer Recurrence In Young Breast Cancer Survivors, Lisa R. Murphy

DNP Research Projects

Abstract

Objective: A significant challenge facing young breast cancer (BC) survivors is learning how to manage fear of cancer recurrence (FCR) during survivorship. Limited tailored FCR interventions and age-appropriate support exist. This Doctor of Nursing (DNP) project, based upon best practice guidelines, aimed to evaluate how a Lifestyle Management Coaching Intervention (LMCI) could help young female BC survivors learn how to decrease and manage their FCR more effectively and experience improved health outcomes.

Method: Eligible participants were female BC survivors aged 18-59 with Stage I-III BC demonstrating elevated baseline FCR screening scores during the extended survival period recruited from the …


Pediatric Otolaryngology Trends In Patient Care Volume During Covid-19: A Survey Study, William R Pellegrini, Anna H Messner, Jessica R Levi Jan 2023

Pediatric Otolaryngology Trends In Patient Care Volume During Covid-19: A Survey Study, William R Pellegrini, Anna H Messner, Jessica R Levi

Faculty, Staff and Students Publications

PURPOSE: To assess changes in outpatient clinic, inpatient consult, and operative volumes among pediatric otolaryngologists in response to the COVID-19 pandemic.

MATERIALS AND METHODS: An online questionnaire was distributed to 535 active members of the American Society of Pediatric Otolaryngology from April 21, 2020, to May 4, 2020. The questionnaire assessed operative and clinical volumes during a two-week period between April 6, 2020, to April 20, 2020, while restrictions on elective surgery were in place, as compared to an average two-week period before the start of the COVID-19 pandemic.

RESULTS: Both outpatient clinic and inpatient consult visit volume decreased significantly …


Nurse-Administered Auricular Point Acupressure For Cancer-Related Pain, Barb Van De Castle, Nada Lukkahatai, Bsn Lynn Billing, Xinran Huang, Hulin Wu, Jingyu Zhang, Salahadin Abdi, Jun Kameoka, Thomas J Smith Jan 2023

Nurse-Administered Auricular Point Acupressure For Cancer-Related Pain, Barb Van De Castle, Nada Lukkahatai, Bsn Lynn Billing, Xinran Huang, Hulin Wu, Jingyu Zhang, Salahadin Abdi, Jun Kameoka, Thomas J Smith

Faculty, Staff and Student Publications

PURPOSE: The study aimed to (1) examine the feasibility of providing a training course on auricular point acupressure (APA) for clinical oncology nurses to integrate APA into real-world nursing care settings, and (2) examine the effectiveness of APA on cancer-related pain (CRP) under usual inpatient oncology ward conditions.

METHODS: This was a 2-phase feasibility study. Phase 1, an in-person, 8 hour training program was provided to oncology nurses. Phase 2, a prospective and feasibility study was conducted to evaluate the integration of APA into nursing care activities to manage CRP. Oncology patients were included if their pain was rated at …


Angiotensin-Ii Stimulating Vs Inhibiting Antihypertensive Drugs And The Risk Of Alzheimer's Disease Or Related Dementia In A Large Cohort Of Older Patients With Colorectal Cancer, Xianglin L Du, Zhuoyun Li, Paul E Schulz Jan 2023

Angiotensin-Ii Stimulating Vs Inhibiting Antihypertensive Drugs And The Risk Of Alzheimer's Disease Or Related Dementia In A Large Cohort Of Older Patients With Colorectal Cancer, Xianglin L Du, Zhuoyun Li, Paul E Schulz

Faculty, Staff and Student Publications

BACKGROUND: Several previous studies showed that patients who received angiotensin II-stimulating antihypertensive medications had a lower incident dementia rate than those angiotensin II-inhibiting antihypertensive users, but no study has been conducted in long-term cancer survivors.

OBJECTIVES: to determine the risk of Alzheimer's disease (AD) and related dementia (ADRD) associated with the types of antihypertensive medications in a large cohort of survivors with colorectal cancer in 2007-2015 with follow-up from 2007 to 2016.

METHODS: We identified 58,699 men and women with colorectal cancer aged 65 or older from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database in 17 SEER areas …


Revisiting Exclusion Of Prior Cancer In Clinical Trials Of Male Breast Cancer, Aniruddha Rathod, Caitlin C Murphy, Asal Rahimi, Sandi L Pruitt Jan 2023

Revisiting Exclusion Of Prior Cancer In Clinical Trials Of Male Breast Cancer, Aniruddha Rathod, Caitlin C Murphy, Asal Rahimi, Sandi L Pruitt

Faculty, Staff and Student Publications

Background: Eligibility criteria for cancer clinical trials present challenges to enrollment. Many trials exclude patients with a prior cancer. This common practice may be especially detrimental to trials of rare cancers, such as male breast cancer, that struggle to accrue adequate numbers of participants. Objectives: to estimate prevalence of prior cancer among men newly diagnosed with breast cancer and describe characteristics of men with prior cancer compared to those without. Methods: We identified men diagnosed with breast cancer between 2011-2015 using population-based data from National Cancer Institute's Surveillance, Epidemiology, and End Results program of cancer registries. We used sequence number …