Medical Specialties Commons^™

A Comparison Of Adjuvant Therapy Modality And Treatment Outcomes Between Appalachian And Non-Appalachian Patients With High-Risk Endometrial Carcinoma, Josie D. Llanora, Gregory S. Hawk, Laura M. Harbin, Sara Lee, Madison Lane, Madison T. Hickey, Elizabeth Pendygraft, Lauren Baldwin, Megan L. Hutchcraft

Markey Cancer Center Faculty Publications

Objective: The incidence and mortality of endometrial cancer is increasing. After surgical staging, patients with high-risk disease often undergo adjuvant treatment, which may include systemic therapy, radiation therapy, or combined modalities. Patients in rural Appalachia have limited access to subspecialty care needed for optimal disease management. This study aims to compare adjuvant treatment regimens and outcomes among patients with high-risk endometrial cancer living in Appalachian and non-Appalachian regions.

Methods: We retrospectively identified 179 patients with high-risk endometrial carcinoma who underwent surgical staging at a single academic medical center and received adjuvant therapy between 2012 and 2019. Patients were identified as …

African American And African-Born Black Women’S Perspectives And Experiences With A Cervical Health Education And Hpv-Self Sampling Intervention, Shania Jones, Abubakari Wuni, Adaeze Aroh, Adebola Olamide Adegboyega

Markey Cancer Center Faculty Publications

Background/Objectives: A combination of cervical cancer prevention education and the provision of HPV self-collection kits has been found to increase the uptake of HPV testing among women. However, there is limited research evaluating the perspectives and experiences of women who have participated in a cancer prevention education and received a complimentary HPV self-collection kit. We report the experiences of women who took part in Health is Wealth: a cervical health intervention and received a complimentary HPV self-sampling kit for cervical cancer screening.

Methods: This pilot qualitative study enrolled twenty-four women who participated in one-on-one semi-structured interviews to provide feedback and …

A High-Throughput Workflow For Assessing Self-Renewal Using Colony Formation Assays, Majd Al-Hamaly, Jessica S. Blackburn

Markey Cancer Center Faculty Publications

The colony formation assay (CFA) is a widely used method to assess the self-renewal capacity of cancer cells and evaluate how this property is affected by drug treatment. This protocol presents a streamlined, high-throughput CFA workflow optimized for T-cell acute lymphoblastic leukemia (T-ALL), making it suitable for large-scale drug screening projects. Colonies are grown in a methylcellulose-based 3D matrix and quantified using an automated analysis pipeline, allowing robust estimation of colony number and size. This cost-effective approach provides a scalable platform for identifying compounds that impair self-renewal, facilitating prioritization of hits for validation in more complex in vivo models.

Analysis Of Facilitators Of And Barriers To Enactment Of State Regulation Of Indoor Tanning By Minors, Carolyn J. Heckman, Anna Mitarotondo, David B. Buller, Julia Berteletti, Kevin Schroth, Jerod L. Stapleton, Robert P. Dellavalle

Markey Cancer Center Faculty Publications

Background: Indoor tanning (IT) causes skin cancers, including potentially deadly melanoma. IT often starts during youth, a critical time for deleterious skin damage. About half of the US states have enacted laws banning IT for minors under age 18.

Purpose: This study reports qualitative findings from interviews with key informants (KIs) involved in IT legislative efforts to identify/describe factors influencing law enactment, based on the multiple streams framework.

Methods: Guided by expert advisors and using snowball-sampling, KIs from 16 states with most recently enacted IT laws regulating minor access and states without restrictions were contacted. In virtual interviews, KIs shared …

Capturing Community Perspectives In A Statewide Cancer Needs Assessment: Online Focus Group Study, Jessica R. Thompson, Keeghan Francis, Caree R. Mcafee, Madeline Brown, Todd Burus, Melinda Rogers, Connie L. Sorrell, Elizabeth A. Westbrook, Lovoria B. Williams, Jennifer Redmond Knight, Elaine Russell, Natalie P. Wilhite, Pamela C. Hull

Markey Cancer Center Faculty Publications

Background: Kentucky has the highest all-site cancer incidence and mortality rates in the United States. Conducting needs assessments in a large geographic area, such as an entire state, poses challenges in collecting qualitative data from diverse rural and urban contexts. In 2021, a steering committee was formed to drive a multimethod, statewide cancer needs assessment (CNA) to identify the future priorities for all cancer-related care in Kentucky.

Objective: We aimed to report on the online focus group component of the CNA by documenting existing community resources and perceived needs across the cancer care continuum. In addition, we aimed to explore …

Characterization Of P53 P.T253i As A Pathogenic Mutation Underlying Li-Fraumeni Syndrome, Nathaniel C. Holcomb, Amanda M. Harrington, Hong Pu, Berina Halilovic, Nathan R. Shelman, Shulin Zhang, Catherine Sears, Terra Armstrong, Brent J. Shelton, Lauren Corum, John A. D'Orazio

Markey Cancer Center Faculty Publications

We identified a germline TP53 c.758C > T (p.T253I) mutation in the TP53 tumor suppressor gene in a pediatric adrenocortical carcinoma (ACC) patient. Characteristic of pathogenic p53 mutations, we observed upregulation of total p53 protein levels in the patient’s ACC and concurrent suppression of the wild-type (WT) TP53 allele. As ACC can be associated with Li-Fraumeni Syndrome (LFS) and the mutation has not yet been linked to LFS, we sought to characterize the functionality of the T253I mutation. We acquired p53^-/-HEK293 cells and stably transduced them with GFP-tagged wild type (T253) or T253I p53 as well as two established …

Cisplatin-Loaded M1 Macrophage-Derived Vesicles Have Anti-Cancer Activity In Osteosarcoma, Namrata Anand, Joseph Robert Mccorkle, David Schweer, Lan Li, Kristen S. Hill, Melissa A. Fath, Derek B. Allison, Christopher L. Richards, Jill M. Kolesar

Markey Cancer Center Faculty Publications

Osteosarcoma (OS) is a relatively rare bone malignancy that primarily affects children and young adults and is associated with significant morbidity and mortality. Cisplatin is a mainstay of treatment, but its efficacy is limited by off-target toxicities. Immunotherapy is not effective due to a poor antigenic tumor microenvironment. Here, we address these challenges by using manufactured M1 macrophage-derived vesicles (MVs) loaded with cisplatin. Human blood and mouse RAW 264.7 M1 macrophages were used to prepare empty (E-MVs) and cisplatin-loaded MVs (C-MVs). Human OS cell lines were used in vitro and in a tibia xenograft mouse model to evaluate the anti-cancer …

Differences In The Cancer Burden And Current Funding Of Nci-Designated Cancer Centers, Todd Burus, Caree R. Mcafee, Pamela C. Hull

Markey Cancer Center Faculty Publications

Importance  National Cancer Institute (NCI)-designated clinical and comprehensive cancer centers are required to define a geographic catchment area (CA) in which they focus research, outreach, and engagement efforts for the purposes of reducing cancer burden, particularly among certain vulnerable populations. A comprehensive analysis of the cancer burden of these catchment areas and their association with cancer center funding through the Cancer Center Support Grant (CCSG) has not been performed.

Objective  To examine CA cancer burden indicators and cancer center CCSG funding during the 2023 federal fiscal year (FY23).

Design, Setting, and Participants  This population-based cross-sectional study assessed cancer center cancer …

Disparities In Human Papillomavirus–Associated Cancer Incidence By Appalachian Residence, Todd Burus, Melina Windon, Yasminka A. Jakubek, Krystle A. Lang Kuhs

Markey Cancer Center Faculty Publications

Importance  Poor socioeconomic conditions and corresponding health disparities have historically characterized the Appalachian region of the US. Low uptake of the human papillomavirus (HPV) vaccine and high rates of cervical cancer have been observed in the region; however, a comprehensive assessment of HPV-associated cancer in Appalachia has not been performed.

Objective  To compare the burden of HPV-associated cancer incidence between the Appalachian and non-Appalachian regions of the US.

Design, Setting, and Participants  This cross-sectional study of HPV-associated cancer incidence rates and trends used the US Cancer Statistics Incidence Analytic Database, covering 99% of the US population and 100% of the …

Examining Associations Between Sociodemographic Characteristics And Ever Breastfed Children, Nhanes 1999–2020, Jessica Amezcua, Lindsey M. West, Camelia Malkami, Marlo M. Vernon, Elinita Pollard, Justin X. Moore

Markey Cancer Center Faculty Publications

Although breastfeeding provides health benefits to both mother and child, this study aimed to explore whether disparities in breastfeeding continue to exist, particularly among non-Hispanic Black (NHB) mothers and children. We performed a cross-sectional analysis among 19,830 children in the United States (US) using the National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2020. Breastfeeding initiation and duration rates increased overall from 1999 to 2020. Children who were ever breastfed were more likely to have higher body weight, older mothers, mothers who did not smoke during pregnancy, a higher family poverty–income ratio (PIR), food security, mothers in …

Examining Geographic Disparity: Variation In Cancer Outcomes Within Appalachia, Todd Burus, Pamela C. Hull, Krystle A. Lang Kuhs, Tianyan Gao, Christine F. Brainson, B. Mark Evers

Markey Cancer Center Faculty Publications

BACKGROUND: 

The Appalachian region of the US extends from the Mississippi Delta to southern New York. Although disparities in Appalachian cancer outcomes have long been observed, recent rates and trends have not been assessed.

STUDY DESIGN: 

We calculated 5-year age-adjusted US cancer incidence and mortality rates for 2017 to 2021, stratified into Appalachian and non-Appalachian populations, as well as Appalachian subregions, using the US Cancer Statistics Incidence Analytics Database and National Center for Health Statistics mortality files. Annual rates for 2004 to 2021 were also calculated.

RESULTS: 

In 2017 to 2021, all-site cancer incidence (466.6; 95% CI 465.5 to 467.6) …

Health Care Access Domains And Treatment As Mediators Of Ovarian Cancer Racial Disparities In Survival: A Structural Equation Modeling Analysis In Seer-Medicare, Clare Meernik, Quan Chen, Lauren E. Wilson, Ashwini Joshi, Fariha Rahman, Maria Pisu, Margaret Liang, Kevin C. Ward, Margaret Gates Kuliszewski, Thomas Tucker, Andrew Berchuck, Bin Huang, Tomi Akinyemiju

Markey Cancer Center Faculty Publications

Racial differences in health care access (HCA) may contribute to disparities in ovarian cancer (OC) survival. We used structural equation models (SEMs) to examine associations between race and HCA domains (affordability, availability, accessibility) in relation to overall and OC-specific mortality. Non-Hispanic (NH)–Black and non-Black (Hispanic, NH-White) women diagnosed with OC in 2008-2015 were identified from Surveillance, Epidemiology, and End Results–Medicare. Cox proportional hazards regression was used to conduct mediation analysis for associations between race and HCA domains with overall and OC-specific mortality. SEM models adjusting for demographic and clinical covariates were used to estimate hazard ratios (HRs) and 95% CIs. …

Cancer-Associated Fibroblast Secreted Dkk1 Promotes The Immunosuppressive Tumor Microenvironment And Colorectal Cancer Resistance To Chemotherapy, Zhijie Yin, Yuning Zhou, Xudong Zhu, Ryan A. Goettl, Chi Wang, Heidi L. Weiss, B. Mark Evers, Qingding Wang

Markey Cancer Center Faculty Publications

Chemotherapy is the cornerstone of treatment for colorectal cancer (CRC). However, acquired resistance can lead to a decrease in the efficiency of chemotherapy. Here, we show that cancer-associated fibroblasts (CAFs) play a critical role in acquired resistance to chemotherapy. Treatment with 5-fluorouracil (5-FU), oxaliplatin, or SN38 (an active metabolite of irinotecan) increased DKK1 expression and secretion, activation of MEK/ERK, and upregulation of p53 in CAFs. Knockdown of p53 or inhibition of MEK/ERK blocked the increase in DKK1 expression induced by chemotherapeutic agents in CAFs. Consistently, elevated DKK1 and phospho-ERK levels were found in CAFs isolated from surgically resected samples of …

Hsp47 Drives Obesity-Associated Breast Cancer Progression By Enhancing Asporin Deposition In Adipose Tissue, Gaofeng Xiong, Daheng He, Dana L. Napier, Jing Chen, Haizhu Shi, Chun Li, Paula J. Hurley, Chi Wang, Haining Zhu, Changcheng Zhou, Therese J. Bocklage, Ren Xu

Markey Cancer Center Faculty Publications

Fibrosis is an important feature of adipose tissue in obese individuals; nevertheless, roles of obesity-associated extracellular matrix (ECM) deposition in breast cancer progression largely remain elusive. Here, we show that expression of Hsp47, a chaperone protein involving collagen secretion, is induced in adipose tissue from obese humans and mice. Adipocyte-specific Hsp47 deletion (Adi-KO) suppresses the high-fat diet (HFD)-induced obesity and mammary tumor progression, accompanied by a reduction in ECM deposition. Matrisome analyses lead to the identification of asporin as a new target of Hsp47 in adipose tissue. Co-immunoprecipitation results confirm that the recruitment of Hsp47 enhances asporin secretion in adipocytes. …

Cancer Advocacy Empowers Appalachian Kentucky Youth, Lauren Hudson Rose, Holly Burke, Olivia Thornsbury, Kameron Jackson, Rebecca Spradlin, Nathan L. Vanderford

Markey Cancer Center Faculty Publications

Kentucky has the highest cancer incidence rate and second highest cancer mortality rate in the United States, and the Appalachian region of the state experiences a disproportionate cancer burden. Cancer-related advocacy, a movement that strives to provide support to cancer patients, families, and organizations, along with policy creation, could help address this disparity by enhancing cancer-related prevention and control efforts. The University of Kentucky Markey Cancer Center’s Appalachian Career Training in Oncology (ACTION) Program partners with the American Cancer Society Cancer Advocacy Network (ACS CAN) to involve Appalachian Kentucky high school and undergraduate students in cancer advocacy activities at the …

Identifying Risk Factors For Adverse Lung Health Outcomes Among Rural Appalachian Women, Jessica R. Thompson, Courtney J. Walker, John C. Flunker, W. Jay Christian, Wayne T. Sanderson, Nancy E. Schoenberg, Steven R. Browning

Markey Cancer Center Faculty Publications

Purpose: Despite high rates of lung disease and lung cancer among women, few studies have focused on adverse lung health risk factors among rural Appalachian women. We aim to describe the prevalence of demographic, behavioral, and economic characteristics among a cohort of rural Appalachian women and ascertain the association between these risk factors and lung function.

Methods: Through a cross-sectional study in two rural Appalachian Kentucky counties (2015–2017), we collected demographics, health history/behaviors, and lung function via pulmonary function tests. Restricting to female participants with interpretable pulmonary function tests (N = 456), we estimated prevalence ratios of the association …

Differential Infiltration Of Key Immune T-Cell Populations Across Malignancies Varying By Immunogenic Potential And The Likelihood Of Response To Immunotherapy., Islam Eljilany, Sam Coleman, Aik Choon Tan, Martin D. Mccarter, John Carpten, Howard Colman, Abdul Rafeh Naqash, Igor Puzanov, Susanne Arnold, Michelle L. Churchman, Daniel Spakowicz, Bodour Salhia, Julian Marin, Shridar Ganesan, Aakrosh Ratan, Craig Shriver, Patrick Hwu, William S. Dalton, George J. Weiner, Jose R. Conejo-Garcia, Paulo Rodriguez, Ahmad A. Tarhini

Markey Cancer Center Faculty Publications

Background: Solid tumors vary by the immunogenic potential of the tumor microenvironment (TME) and the likelihood of response to immunotherapy. The emerging literature has identified key immune cell populations that significantly impact immune activation or suppression within the TME. This study investigated candidate T-cell populations and their differential infiltration within different tumor types as estimated from mRNA co-expression levels of the corresponding cellular markers.

Methods: We analyzed the mRNA co-expression levels of cellular biomarkers that define stem-like tumor-infiltrating lymphocytes (TILs), tissue-resident memory T-cells (TRM), early dysfunctional T-cells, late dysfunctional T-cells, activated-potentially anti-tumor (APA) T-cells and Butyrophilin 3A (BTN3A) isoforms, utilizing …

Physicochemical Property Effects On Immune Modulating Polymeric Nanoparticles: Potential Applications In Spinal Cord Injury, Daniel J. Kolpek, Jaechang Kim, Hisham Mohammed, John C. Gensel, Jonghyuck Park

Markey Cancer Center Faculty Publications

Nanoparticles (NPs) offer promising potential as therapeutic agents for inflammation-related diseases, owing to their capabilities in drug delivery and immune modulation. In preclinical studies focusing on spinal cord injury (SCI), polymeric NPs have demonstrated the ability to reprogram innate immune cells. This reprogramming results in redirecting immune cells away from the injury site, downregulating pro-inflammatory signaling, and promoting a regenerative environment post-injury. However, to fully understand the mechanisms driving these effects and maximize therapeutic efficacy, it is crucial to assess NP interactions with innate immune cells. This review examines how the physicochemical properties of polymeric NPs influence their modulation of …

Independent Evolution Of Oleate Hydratase Clades In Bacillales Reflects Molecular Convergence, Robert J. Neff, Priscilla C. Lages, Shannon K. Donworth, James D. Brien, Christopher D. Radka

Markey Cancer Center Faculty Publications

Oleate hydratase (OhyA), a flavoenzyme that catalyzes the hydration of unsaturated fatty acids, has been identified in various Bacillales organisms, including those in the Listeria, Lysinibacillus, Paenibacillus, and Staphylococcus genera. In this study, we combine structural biology with molecular and phylogenetic analyses to investigate the evolutionary dynamics of the OhyA protein family within the Bacillales order. Our evolutionary analysis reveals two distinct OhyA clades (clade I and clade II) within Bacillales that, while sharing catalytic function, exhibit significant genomic and structural differences. Our findings suggest that these OhyA clades originated from independent evolutionary processes through convergent evolution rather than gene …

Impact Of Gut Microbiota And Its Metabolites On Immunometabolism In Colorectal Cancer, Madison Flory, Paloma Bravo, Asfaqul Alam

Markey Cancer Center Faculty Publications

Colorectal cancer (CRC) is highly prevalent, accounting for approximately one-tenth of cancer cases and deaths globally. It stands as the second most deadly and third most common cancer type. Although the gut microbiota has been implicated in CRC carcinogenesis for the last several decades, it remains one of the least understood risk factors for CRC development, as the gut microbiota is highly diverse and variable. Many studies have uncovered unique microbial signatures in CRC patients compared with healthy matched controls, with variations dependent on patient age, disease stage, and location. In addition, mechanistic studies revealed that tumor-associated bacteria produce diverse …

Correction: Nac1 Promotes Stemness And Regulates Myeloid‑Derived Cell Status In Triple‑Negative Breast Cancer., Chrispus Ngule, Ruyi Shi, Xingcong Ren, Hongyan Jia, Felix Oyelami, Dong Li, Younhee Park, Jinhwan Kim, Hami Hemati, Yi Zhang, Xiaofang Xiong, Andrew Shinkle, Nathan L. Vanderford, Sara Bachert, Binhua P. Zhou, Jianlong Wang, Jianxun Song, Xia Liu, Jin-Ming Yang

Markey Cancer Center Faculty Publications

No abstract provided.

Conditional Deletion Of Ceacam1 In Hepatic Stellate Cells Causes Their Activation, Harrison T. Muturi, Hilda E. Ghadieh, Suman Asalla, Sumona G. Lester, Getachew D. Belew, Sobia Zaidi, Raziyeh Abdolahipour, Abhishek P. Shrestha, Agnes O. Portuphy, Hannah L. Stankus, Raghd Abu Helal, Stefaan Verhulst, Sergio Duarte, Ali Zarrinpar, Leo A. Van Grunsven, Scott L. Friedman, Robert F. Schwabe, Terry D. Hinds, Jr., Sivarajan Kumarasamy, Sonia M. Najjar

Markey Cancer Center Faculty Publications

Objectives: Hepatic CEACAM1 expression declines with advanced hepatic fibrosis stage in patients with metabolic dysfunction-associated steatohepatitis (MASH). Global and hepatocyte-specific deletions of Ceacam1 impair insulin clearance to cause hepatic insulin resistance and steatosis. They also cause hepatic inflammation and fibrosis, a condition characterized by excessive collagen production from activated hepatic stellate cells (HSCs). Given the positive effect of PPARg on CEACAM1 transcription and on HSCs quiescence, the current studies investigated whether CEACAM1 loss from HSCs causes their activation.

Methods: We examined whether lentiviral shRNA-mediated CEACAM1 donwregulation (KD-LX2) activates cultured human LX2 stellate cells. We also generated LratCre þ Cc1fl/fl mutants …

Integrin Α6Β4 Upregulates Ptprz1 Through Uchl1-Mediated Hif-1Α Nuclear Accumulation To Promote Triple-Negative Breast Cancer Cell Invasive Properties, Min Chen, Parvanee A. Karimpour, Andrew Elliott, Daheng He, Teresa Knifley, Jinpeng Liu, Chi Wang, Kathleen L. O’Connor

Markey Cancer Center Faculty Publications

Integrin α6β4 drives triple-negative breast cancer (TNBC) aggressiveness through the transcriptional regulation of key genes. Here, we investigated how integrin α6β4 regulates protein tyrosine phosphatase receptor type Z1 (PTPRZ1). Using stable re-expression of integrin β4 (ITGB4) in cells naturally devoid of integrin α6β4 or knockdown or knockout (KO) of ITGB4, we found that integrin α6β4 regulates PTPRZ1 expression. To gain mechanistic insight, we focused on Hif-1α due to the impact of integrin α6β4 on a hypoxia-associated signature. We found that nuclear localization of Hif-1α, but not Hif-2α, was substantially enhanced with integrin α6β4 signaling. Hif-1α knockdown by shRNA or chemical …

Knockdown Of Ketohexokinase Versus Inhibition Of Its Kinase Activity Exert Divergent Effects On Fructose Metabolism, Se-Hyung Park, Taghreed Fadhul, Lindsey R. Conroy, Harrison A. Clarke, Ramon Sun, Kristina Wallenius, Jeremie Boucher, Gavin O'Mahony, Alessandro Boianelli, Marie Persson, Sunhee Jung, Cholsoon Jang, Analia S. Loria, Genesee J. Martinez, Zachary A. Kipp, Evelyn A. Bates, Terry D. Hinds Jr., Senad Divanovic, Samir Softic

Markey Cancer Center Faculty Publications

Excessive fructose intake is a risk factor for the development of obesity and its complications. Targeting ketohexokinase (KHK), the first enzyme of fructose metabolism, has been investigated for the management of metabolic dysfunction–associated steatotic liver disease (MASLD). We compared the effects of systemic, small molecule inhibitor of KHK enzymatic activity with hepatocyte-specific, N-acetylgalactosamine siRNA–mediated knockdown of KHK in mice on an HFD. We measured KHK enzymatic activity, extensively quantified glycogen accumulation, performed RNA-Seq analysis, and enumerated hepatic metabolites using mass spectrometry. Both KHK siRNA and KHK inhibitor led to an improvement in liver steatosis; however, via substantially different mechanisms, KHK …

Cost-Effectiveness Of Point Of Care Smoking Cessation Interventions In Oncology Clinics., Kerri A. Mullen, Kelly Hurley, Shelley Hewitson, Joshua Scoville, Alyssa Grant, Kednapa Thavorn, Eshwar Kumar, Graham W. Warren

Markey Cancer Center Faculty Publications

BACKGROUND: We examined the cost-effectiveness of providing systematic smoking cessation interventions to oncology patients at point-of-care.

METHODS: A decision analytic model was completed from the healthcare payer's perspective and included all incident cancer cases involving patients who smoke in New Brunswick, Canada (n = 1040), cancer site stratifications, and risks of mortality, continued smoking, and cancer treatment failure over one year. Usual care (no cessation support) was compared to the standard Ottawa Model for Smoking Cessation (OMSC) intervention, and to OMSC plus unlimited cost-free stop smoking medication (OMSC + SSM), including nicotine replacement therapy, varenicline, or bupropion. Primary outcomes were …

Predicting The Pathway Involvement Of All Pathway And Associated Compound Entries Defined In The Kyoto Encyclopedia Of Genes And Genomes, Erik D. Huckvale, Hunter Moseley

Markey Cancer Center Faculty Publications

Background/Objectives: Predicting the biochemical pathway involvement of a compound could facilitate the interpretation of biological and biomedical research. Prior prediction approaches have largely focused on metabolism, training machine learning models to solely predict based on metabolic pathways. However, there are many other types of pathways in cells and organisms that are of interest to biologists. Methods: While several publications have made use of the metabolites and metabolic pathways available in the Kyoto Encyclopedia of Genes and Genomes (KEGG), we downloaded all the compound entries with pathway annotations available in the KEGG. From these data, we constructed a dataset where each …

Upregulation Of Fatty Acid Synthase Increases Activity Of Β-Catenin And Expression Of Notum To Enhance Stem-Like Properties Of Colorectal Cancer Cells, Courtney O. Kelson, Josiane Weber Tessmann, Mariah E. Geisen, Daheng He, Chi Wang, Tianyan Gao, B. Mark Evers, Yekaterina Y. Zaytseva

Markey Cancer Center Faculty Publications

Dysregulated fatty acid metabolism is an attractive therapeutic target for colorectal cancer (CRC). We previously reported that fatty acid synthase (FASN), a key enzyme of de novo synthesis, promotes the initiation and progression of CRC. However, the mechanisms of how upregulation of FASN promotes the initiation and progression of CRC are not completely understood. Here, using Apc/VillinCre and ApcMin mouse models, we show that upregulation of FASN is associated with an increase in activity of β-catenin and expression of multiple stem cell markers, including Notum. Genetic and pharmacological downregulation of FASN in mouse adenoma organoids decreases the activation of β-catenin …

The Absence Of Cxcl10 Activity Does Not Affect The Capability Of Cd8+ T Cells To Migrate And Eliminate The Tissue Cysts Of Toxoplasma Gondii From The Brains Of Chronically Infected Mice, Rajesh Mani, Yasuhiro Suzuki

Markey Cancer Center Faculty Publications

Toxoplasma gondii forms tissue cysts in neurons and astrocytes in the brain to establish chronic infection, and astrocytes express the CXCL10 chemokine in chronically infected mice. Since chemokines mediate the migration of T cells to attack their targets, and since CXCL10 plays key roles in T cell-mediated control of the proliferation of tachyzoites (the acute stage form) of T. gondii during the acute stage of infection, we examined whether CXCL10 is involved in recruiting anti-cyst CD8+ cytotoxic T cells to eliminate the cysts in their brains. We employed adoptive transfer of CD8+ immune T cells to infected, T cell-deficient SCID …

The Impact Of Pdcd4, A Translation Inhibitor, On Drug Resistance, Qing Wang, Hsin-Sheng Yang

Markey Cancer Center Faculty Publications

Programmed cell death 4 (Pdcd4) is a tumor suppressor, which has been demonstrated to efficiently suppress tumorigenesis. Biochemically, Pdcd4 binds with translation initiation factor 4A and represses protein translation. Beyond its role in tumor suppression, growing evidence suggests that Pdcd4 enhances the chemosensitivity of several anticancer drugs. To date, numerous translational targets of Pdcd4 have been identified. These targets govern important signal transduction pathways, and their attenuation may improve chemosensitivity or overcome drug resistance. This review will discuss the signal transduction pathways regulated by Pdcd4 and the potential mechanisms through which Pdcd4 enhances chemosensitivity or counteracts drug resistance.

Association Between Obesity And Risk Of Total And Obesity-Related Cancer In People With Incident Cardiovascular Disease., Sarah Malik, Avirup Guha, Xiaoling Wang, Neal L. Weintraub, Ryan Harris, Biplab Datta, Justin Moore, Priyanshu Nain, Sagar A. Patel, Steven Coughlin, Elizabeth Polter, Anna Prizment, Anne Blaes, Roberta Florido, Shelby Kutty, Alvaro Alonso, Corinne E. Joshu, Elizabeth A. Platz

Markey Cancer Center Faculty Publications

BACKGROUND: Cardiovascular disease (CVD) and cancer frequently co-occur due to shared risk factors such as obesity, which is linked to CVD and 14 cancer types. This study explores whether CVD pathophysiologies, combined with obesity, increase cancer risk, impacting clinical management.

METHODS AND RESULTS: Data from the ARIC (Atherosclerosis Risk in Communities) study, spanning 28 years, were analyzed. The cohort included 5127 participants with incident CVD (myocardial infarction, stroke, heart failure, coronary heart disease), of whom 1511 developed a first primary cancer. Follow-up began at CVD diagnosis after Visit 1. Obesity was assessed using body mass index, waist circumference, and waist-to-hip …