Medical Specialties Commons^™

Twenty-First Century Data Systems: Evolving Cancer Registries To A Learning Health System, Peter P. Yu, W. Scott Campbell, Eric B. Durbin, Lawrence N. Shulman, Jeremy L. Warner

Markey Cancer Center Faculty Publications

Introduction: Oncology is a data-rich environment reflecting the increasing incidence of cancer in the US aging population, transformation of cancer into a chronic disease due to advances in treatment, and the emergence of new data categories such as genomics. Concomitantly, healthcare systems are challenged to meet regulatory and voluntary reporting of cancer data to support government, quality certification, research and strategic partnership needs.

Materials and Methods: The National Academies of Science, Engineering, and Medicine organized a workshop entitled “Enabling 21st-century applications for cancer surveillance through enhanced registries and beyond” with representation from NCI Comprehensive Cancer Centers, oncology and medical informatics …

Discrimination Distress And Current Combustible And Non-Combustible Tobacco Product Use Among Us Youth, 2023, Meman Diaby, Osayande Agbonlahor, Maggie K. Richardson, Joy L. Hart, Shyanika W. Rose, Delvon T. Mattingly

Markey Cancer Center Faculty Publications

Introduction: Discrimination is the unfair treatment of people based on their identity. Youth who experience discrimination may cope with associated distress by using tobacco products, with amplified health consequences depending on the type of product.

Methods: We used data from the 2023 National Youth Tobacco Survey (n = 22 069) and derived an overall continuous measure from the 15-item Adolescent Discrimination Distress Index, as well as three continuous discrimination distress sub-indices: educational, institutional, and peer (range for each: 0–5). We defined current tobacco use as two outcomes: any past 30-day use of combustible (cigarettes, cigars, hookah, roll- your-own, pipe, bidis) …

Developing A Multidisciplinary Pediatric Cancer Predisposition Service At A Mid-Sized Children’S Hospital, Amanda M. Harrington, John August D'Orazio

Markey Cancer Center Faculty Publications

Roughly one in ten children and young adults diagnosed with cancer has an underlying genetic variant that may explain his/her malignancy. It is critical to identify patients with cancer predisposition syndromes (CPSs) to provide personalized cancer treatment, surveillance, counseling, psychosocial support, and in some cases, risk-reducing interventions to maximize long-term outcomes. Over the past five years, we developed a comprehensive pediatric CPS program at our institution. We engaged our institutional adult cancer center for clinical cancer genetic counseling services and needed research shared resource facilities. We also initiated a clinical study called “Project Inherited Cancer Risk” (PICR) to identify pediatric …

Colon Cancer In Appalachian Kentucky: Unique Genetic, Microbiome And Obesity Findings In A Cohort Comparison, Zeta Chow, Jinpeng Liu, Daheng He, Chi Wang, Tong Gan, Akila Mansour, Nuha Shaker, Caroline Dravillas, Rebecca Hoyd, Eric B. Durbin, Dana L. Napier, Tianyan Gao, Kurt Schaberg, Lyen Huang, Neli Ulrich, Erin Siegel, Stephen Edge, Linda Cook, Bodour Salhia, Michelle L. Churchman, Jill Kolesar, Daniel Spakowicz, B. Mark Evers, Therese J. Bocklage

Markey Cancer Center Faculty Publications

We investigated colon cancer genomics and microenvironmental features in the Appalachian Kentucky population, a group with the highest incidence of colon cancer in the United States. We assessed two inter-related risk factors for colon cancer (obesity and abnormal gut bacterial microbiome) and their genetic associations within this population. To evaluate potential unique characteristics of the high-incidence cohort, we compared 99 propensity-matched colon cancer tumors from Appalachian Kentucky patients to 95 non-Appalachian patient tumors to evaluate driver mutations, differentially expressed genes (DEGs), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, Catalogue of Somatic Mutations in Cancer (COSMIC) mutational signatures, immune cell …

Hexavalent Chromium Promotes Malignant Transformation Via Enhanced Translation Of Suv39h1, Yiwei Gu, Yanan Cao, Qing Ye, Yujing Zhang, Zhishan Wang, Chengfeng Yang, Side Liu, Qing-Bai She

Markey Cancer Center Faculty Publications

Hexavalent chromium [Cr(VI)] is a widespread environmental carcinogen linked to lung cancer and other malignancies. Although genetic and epigenetic mechanisms of Cr(VI)-induced carcinogenesis have been extensively investigated, the role of translational control has remained largely unexplored. Here, we show that chronic low-dose Cr(VI) exposure in BEAS-2BR human bronchial epithelial cells activates eIF4E-driven cap-dependent translation through mTORC1-mediated phosphorylation and inactivation of the translational repressor 4E-BP1. Pharmacological inhibition of this pathway markedly suppresses Cr(VI)-induced cell transformation, cancer stem cell (CSC)-like properties, and DNA damage. Comparable inhibitory effects are observed following raptor knockdown, which disrupts mTORC1, or expression of a constitutively active non-phosphorylatable …

Rna-Micelles As Self-Assembling Structures For Efficient Co-Delivery Of Synergistic Sirna And Nucleoside Analogues To Treat Crc Lung Metastasis, Kai Jin, Piotr G. Rychahou, Daniel W. Binzel, B. Mark Evers, Peixuan Guo

Markey Cancer Center Faculty Publications

SiRNA has been widely studied in cancer gene silencing over the last 25 years. However, few siRNA-based therapeutics have been approved by the FDA. An RNA-micelle platform provides a powerful therapeutic tool through simple one-step, high-yield production that is capable of efficient colorectal cancer lung metastasis treatment, a current lethal condition with a short survival rate post-diagnosis. Here, it is reported that the use of RNA-micelles co-carrying siRNA and nucleoside analogues to completely inhibit lung metastasis of colorectal cancer (CRC). The major advantage of the RNA-micelle is the successful co-delivery of siRNA and chemotherapeutic agent in a single delivery vehicle …

Geographic Clusters Of Human Papillomavirus-Associated Cancer Incidence In The Us, 2008–2022, Todd Burus, Krystle A. Lang Kuhs, Ashish A. Deshmukh, Haluk Damgacioglu

Markey Cancer Center Faculty Publications

Objective: Despite known state and regional differences, United States (US) county-level patterns of human papillomavirus (HPV)-associated cancer incidence remain unexplored. Methods: In this cross-sectional study, we analyzed US county-level HPV-associated cancer incidence rates from 2008 to 2022 using the US Cancer Statistics Incidence Analytic Database to identify geographic clusters of high and low incidence. Clusters were identified using the Getis-Ord Gi* statistic and assessed for differences in cluster-level sociodemographic characteristics and sex-and-site-specific incidence. Results: We found 373 hot spot and 409 cold spot counties, with median incidence rates of 16.14 and 10.62 per 100,000, respectively. Hot spot counties were particularly …

Case Report: Prolonged Response To Cabozantinib And Pembrolizumab In Treatment-Refractory Metastatic Pancreatic Ductal Adenocarcinoma, Anna M. Reagan, Hannah G. Mcdonald, Jaewon Kang, Hoda Saghaeiannejad Esfahani, Caroline G. Wright, Charles J. Bailey, Carleton S. Ellis, Kaylyn R. Collette, Reema A. Patel, Mayte Murillo, Samantha F. Stokley, Michael J. Cavnar, Prakash Pandalai, Mautin T. Barry-Hundeyin, Jessica Moss, Joseph Kim

Markey Cancer Center Faculty Publications

Immunotherapy has yet to demonstrate durable efficacy in pancreatic ductal adenocarcinoma (PDAC) despite the fact that pancreatic cancer cells have higher levels of immune checkpoint expression than other cancer cell types in which immunotherapy efficacy has been well established. We observed effective cytotoxicity with the combination therapy of pembrolizumab (an anti-PD-1 monoclonal antibody, mAb) and cabozantinib (an anti-MET small molecule) in vivo. This served as the basis for an investigator-initiated phase II clinical trial (NCT05052723). The trial was open to patients with treatment-refractory metastatic PDAC with a single-arm treatment protocol of pembrolizumab and cabozantinib. Here, we report the case of …

Survival Of Patients Diagnosed With Cancer During The Covid-19 Pandemic, Todd Burus, Haluk Damgacioglu, Bin Huang, Thomas C. Tucker, Ashish A. Deshmukh, Krystle A. Lang Kuhs

Markey Cancer Center Faculty Publications

Importance  The effects of COVID-19 pandemic–related disruptions on cancer diagnosis in the US have been widely observed, but their impact on short-term survival has not been assessed.

Objective  To examine 1-year cause-specific survival (CSS) rates among patients diagnosed with cancer during 2020 and 2021 using high-quality cancer registry data.

Design, Setting, and Participants  This population-based cohort study of cancer survival between 2015 and 2021 used the Surveillance, Epidemiology, and End Results 21 Registries (SEER-21) database. The population included individuals with an invasive cancer diagnosis and complete follow-up reported to registries included in SEER-21 between January 1, 2015, and December 31, …

A Phase 1 Dose Escalation Of Lapatinib And Paclitaxel In Recurrent Ovarian Cancer, Connie D. Cao, Joseph Robert Mccorkle, Donglin Yan, Hoda Saghaeiannejad Esfahani, Rani Jayswal, Dava W. Piecoro, Ning Li, Lauren Baldwin, Rachel W. Miller, Christopher P. Desimone, Charles S. Dietrich, Frederick R. Ueland, Jill M. Kolesar

Markey Cancer Center Faculty Publications

Objective: The development of ABCB1-mediated resistance limits the clinical efficacy of paclitaxel. Lapatinib is a small-molecule reversible tyrosine kinase and ABCB1 inhibitor that could prevent resistance. Our objective was to determine a recommended phase 2 dose (RP2D) of the combination of paclitaxel and lapatinib.

Methods: A phase 1 dose-escalation study utilizing a Bayesian optimal interval (BOIN) design in recurrent ovarian cancer patients was conducted. Patients were pretreated with pulsed lapatinib in the 48 h preceding weekly paclitaxel (80 mg/m²) in 28-day cycles for up to three cycles. We evaluated three lapatinib doses, escalating from 750 to 2000 mg …

Dna-Pkcs Promotes Therapy Resistance And Metastatic Recurrence In Neuroblastoma, Mahnaz Norouzi, Subin Kim, Beibei Zhu, Chi Wang, Natalie Wu, Katherine Somers, Eddy Shih-Hsin Yang, B. Mark Evers, Eric J. Rellinger, Piotr G. Rychahou

Markey Cancer Center Faculty Publications

Purpose: High-risk neuroblastoma presents a serious clinical challenge with survival rates below 50%. Disease relapse most commonly occurs at distant metastatic sites and remains the primary driver of poor outcomes, emphasizing the need for therapies to target drivers of relapse.

Experimental design: This study identified DNA-PKcs as a critical determinant of poor survival and metastatic relapse in neuroblastoma patients. We evaluated which therapeutic modality—chemotherapy or radiotherapy—when combined with DNA-PKcs inhibition, more effectively reduces metastatic burden and prevents recurrence.

Results: Colony-forming assays revealed that established neuroblastoma colonies resist doxorubicin alone and require high-dose doxorubicin paired with DNA-PKcs inhibition to suppress progression. …

A Unique Protein Adjuvant For Precision Immunotherapy To Prevent Recurrence Of Surgically Resected Colorectal Cancer, Yasuhiro Suzuki, Rajesh Mani, B. Mark Evers

Markey Cancer Center Faculty Publications

Effectively activating protective CD8⁺ T cell immunity specifically against cancer antigens is an important pathway to prevent the growth of various types of cancers. A major obstacle in this approach is variations in cancer antigens among patients. A valuable material to overcome the antigen variation among cancer patients is the use of each individual’s own cancer cells for immunization. In colorectal cancer (CRC), approximately one-third of the patients who receive curative surgical resection have a recurrence of cancer. Therefore, the use of surgically resected CRC for immunotherapy to specifically activate the protective CD8⁺ T cells against their own …

Mental Health Needs Of Families Of Patients In Intensive Care Units And The Role Of Mobile Health: Survey Study, Anthony Faiola, Saira Soroya, Zhonglin Hao, Reinhold Munker

Markey Cancer Center Faculty Publications

Background: The experiences of patients with COVID-19 and their families manifested the most devastating effects of family separation since the 1918 Spanish influenza pandemic and, with it, a call for solutions to patient isolation and its effect on family mental health.

Objective: This study examined the recent experiences of families of critical care (intensive care unit; ICU) patients related to anxiety and depression (AD), satisfaction with clinician-family communication, and counseling from mental health and social services. This study explored correlations between these factors and family interest in mobile health (mHealth) designed to improve information flow and communication from patient bedside …

Survival Outcomes Of First-Line Therapy In De Novo Metastatic Urothelial Carcinoma With Histologic Subtypes: A National Cancer Database Analysis, Zin W. Myint, Feitong Lei, Bin Huang

Markey Cancer Center Faculty Publications

Background: Urothelial carcinoma with histologic subtypes represent an aggressive and understudied population frequently excluded from prospective clinical trials. Evidence guiding optimal first-line systemic therapy in de novo metastatic disease with histologic subtypes remains limited.

Method: Patients with de novo stage IV urothelial carcinoma with histologic subtypes diagnosed between 2016 and 2021 were identified from the National Cancer Database (NCDB). Eligible patients received first-line chemotherapy, immunotherapy, or concurrent chemoimmunotherapy (both modalities initiated within 30 days). Overall survival (OS) was compared across groups using Kaplan–Meier methods and compared using log-rank tests and multivariable Cox regression. Result: Among 800 patients, 596 (74.5%) received …

Person‑Level Health Factors Partially Mediate The Association Between Lesbian, Gay, Or Bisexual (Lgb) Identity, Allostatic Load, And Cancer Mortality In Nhanes, Justin Xavier Moore, Alisha Patel, Missy Spears, Tracy Casanova, Heidi L. Weiss, Marvin E. Langston, Keith J. Watts, Donte Boyd, Prajakta Adsul, Meredith S. Duncan, Sydney Howard

Markey Cancer Center Faculty Publications

Purpose: Individuals identifying as Lesbian, Gay, or Bisexual (LGB) with high allostatic load have more than double the cancer mortality risk of heterosexual individuals with high allostatic load. This study explored how person-level health factors mediate the relationship between individuals identifying as LGB with high allostatic load and subsequent risk of cancer mortality.

Methods: We conducted a retrospective analysis of 12,470 participants in the National Health and Nutrition Examination Survey (2001–2010) linked to the National Death Index through 31 December 2019. Survey-weighted Cox regression assessed associations of individuals identifying as LGB and allostatic load with cancer mortality. Person-level health factors …

Oncology Clinicians’ Attitudes On Hormonal Therapy After Chemoradiotherapy For Cervical Cancer, Morgan S. Levy, Marilyn Huang, Charles S. Dietrich, Denise Fabian

Markey Cancer Center Faculty Publications

No abstract provided.

Assessing The Value Of Sequential Next-Generation Sequencing And Multiple Molecular Tumor Board Reviews For Patients With Solid-Tumor Malignancies, Allison L. Swiecki-Sikora, Lydia Williams, Ning Li, Donglin Yan, Evan Bryon, Derek B. Allison, Rachel W. Miller, Charles S. Dietrich, Jill M. Kolesar

Markey Cancer Center Faculty Publications

Purpose: Multidisciplinary molecular tumor boards (MTBs) have demonstrated improved clinical outcomes in various malignancies. Sequential next-generation sequencing (NGS) is widely performed at the time of recurrence, which may lead to multiple MTB reviews. This study assessed the clinical benefit of multiple MTB reviews for sequential NGS.   Methods: A retrospective cohort review was performed to compare patients reviewed once at a single-institution MTB and those reviewed multiple times for the same diagnosis with sequential NGS between January 2016 and December 2023. Demographics were compared, and regression and survival analysis was performed.   Results: In all, 3,702 patients were included, 3,446 (91.6%) were …

Case Report: Prostate Adenocarcinoma With Peritoneal Carcinomatosis And Elevated Cea Mimicking Colorectal Cancer: A Diagnostic Dilemma, Hala Majeed, Nathan R. Shelman, Jitesh A. Patel, Janeesh S. Veedu, Insija I. Selene, Ashlyn Whitesell, Zin W. Myint

Markey Cancer Center Faculty Publications

This case report describes an exceptionally rare manifestation of prostate adenocarcinoma presenting with peritoneal carcinomatosis, rectal obstruction, and markedly elevated carcinoembryonic antigen (CEA), closely mimicking colorectal cancer. A 65-year-old man with localized high-grade prostate adenocarcinoma (Gleason 4 + 4) underwent robotic prostatectomy in November 2020, followed by salvage radiation and stereotactic body radiation therapy for early biochemical recurrence. He achieved an excellent response to androgen deprivation therapy (ADT) combined with abiraterone and prednisone, maintaining an undetectable prostate-specific antigen (PSA) level for over 2 years. In late 2024, the patient developed hematochezia, narrow stools, and abdominal pain. Imaging revealed a rectal …

Eef2k Promotes Immune Evasion In Melanoma Via Cyclin D1–Mediated Stabilization Of Pd-L1, Yijie Ren, Darby J. Ballard, Anil Kumar, Andy F. Song, Mitiksha Gupta, Xiaofang Xiong, Xingcong Ren, Jugal Kishore Das, Jin-Ming Yang, Jianxun Song

Markey Cancer Center Faculty Publications

Eukaryotic elongation factor 2 kinase (eEF2K) is a stress-responsive regulator of protein synthesis implicated in melanoma progression, but its role in tumor immune evasion remains poorly defined. We investigated how eEF2K influences programmed death ligand 1 (PD-L1) expression through modulation of Cyclin D1. We analyzed gene expression and dependency datasets from The Cancer Genome Atlas and the Cancer Dependency Map. Protein–protein interactions were assessed by co-immunoprecipitation. Cyclin D1 was inhibited pharmacologically with palbociclib. Immune responses were evaluated in murine B16-OVA and human A2058 melanoma models using flow cytometry and immunohistochemistry after genetic or pharmacologic modulation of eEF2K and Cyclin D1. …

Therapeutic Applications Of A Novel Humanized Monoclonal Antibody Targeting Chemokine Receptor Ccr9 In Pancreatic Cancer, Hannah G. Mcdonald, Anna M. Reagan, Charles J. Bailey, Mei Gao, Muqiang Gao, Angelica L. Solomon, Michael J. Cavnar, Prakash Pandalai, Mautin Barry-Hundeyin, Megan Harper, Justin A. Rueckert, Ángela Turrero, Araceli Tobio, Anxo Vidal, Daniel Roca-Lema, Elia Álvarez-Coiradas, Pablo Garrido, Laureano Simón, Joseph Kim

Markey Cancer Center Faculty Publications

The relative failure of immune checkpoint inhibitors in pancreatic ductal adenocarcinoma (PDAC) despite having a dense, immunosuppressive tumor microenvironment highlights the need to target alternate/escape pathways. We have previously examined C–C chemokine receptor type 9 (CCR9) as a candidate immune checkpoint and developed a targeted, humanized monoclonal antibody (SRB2). Cytotoxicity of SRB2 was evaluated in vitro and in vivo. CCR9 expression on PDAC cells/tissues, immune components of patient-derived organoids (PDOs), and antibody-dependent cell-mediated cytotoxicity were examined. In PANC-1 and MIA PaCa-2 cell lines, we demonstrated highest CCR9 expression; however, no direct cytotoxic effect was observed with SRB2 treatment. In PANC-1 …

An Agrin-Yap/Taz Rigidity Sensing Module Drives Egfr-Addicted Lung Tumorigenesis., Reza Bayat Mokhtari, Divyaleka Sampath, Paige Eversole, Melissa Ong Yu Lin, Dmitriy A. Bosykh, Gandhi T. K. Boopathy, Aravind Sivakumar, Cheng-Chun Wang, Ramesh Kumar, Joe Yeong Poh Sheng, Ellen Karasik, Barbara A. Foster, Han Yu, Xiang Ling, Wenjie Wu, Fengzhi Li, Zoë Weaver Ohler, Christine Fillmore Brainson, David W. Goodrich, Wanjin Hong, Sayan Chakraborty

Markey Cancer Center Faculty Publications

Despite epidermal growth factor receptor (EGFR) is a pivotal oncogene for several cancers, including lung adenocarcinoma (LUAD), how it senses extracellular matrix (ECM) rigidity remain elusive in the context of the increasing role of tissue rigidity on various hallmarks of cancer development. Here it is shown that EGFR dictates tumorigenic agrin expression in lung cancer cell lines, genetically engineered EGFR-driven mouse models, and human specimens. Agrin expression confers substrate stiffness-dependent oncogenic attributes to EGFR-reliant cancer cells. Mechanistically, agrin mechanoactivates EGFR through epidermal growth factor (EGF)-dependent and independent modes, thereby sensitizing its activity toward localized cancer cell-ECM adherence and bulk rigidity …

Steroid Receptors And Coregulators: Dissemination Of Sex Differences And Emerging Technologies, Sally Pauss, Evelyn A. Bates, Genesee J. Martinez, Zane T. Bates, Zachary A. Kipp, Cassandra D. Gipson, Terry D. Hinds Jr.

Markey Cancer Center Faculty Publications

Steroid receptors are ligand-induced transcription factors that have broad functions among all living animal species, ranging from control of sex differences, body weight, stress responses, and many others. Their binding to coregulator proteins is regulated by corepressors and coactivators that interchange upon stimulation with a ligand. Coregulator proteins are an imperative and understudied aspect of steroid receptor signaling. Here, we discuss steroid receptor basics from protein domain structures that allow them to interact with coregulators and other proteins, their essential functions as transcription factors, and other elemental protein–protein interactions. We deliberate about the mechanisms that coregulators control in steroid receptor …

Lysyl Hydroxylase 2 Glucosylates Collagen Vi To Drive Lung Cancer Progression, Shike Wang, Houfu Guo, Reo Fukushima, Masahiko Terajima, Min Liu, Guan-Yu Xiao, Lenka Koudelková, Chao Wu, Xin Liu, Jiang Yu, Emma Burris, Jun Xu, Alvise Schiavinato, William K. Russell, Mitsuo Yamauchi, Xiaochao Tan

Markey Cancer Center Faculty Publications

Lysyl hydroxylase 2 (LH2) is highly expressed in multiple tumor types and accelerates disease progression by hydroxylating lysine residues on fibrillar collagen telopeptides to generate stable collagen cross links in tumor stroma. Here, we show that a galactosylhydroxylysyl glucosyltransferase (GGT) domain on LH2 modified type-VI collagen (Col6) to promote lung adenocarcinoma (LUAD) growth and metastasis. In tumors generated by LUAD cells lacking LH2 GGT domain activity, stroma was less stiff, and stable types of collagen cross links were reduced. Mass spectrometric analysis of total and glycosylated peptides in parental and GGT-inactive tumor samples identified Col6 chain α3 (Col6a3), a component …

Insulin Receptor Responsiveness Governs Tgfβ-Induced Hepatic Stellate Cell Activation: Insulin Resistance Instigates Liver Fibrosis, Wang-Hsin Lee, Evelyn A. Bates, Zachary A. Kipp, Sally Pauss, Genesee J. Martinez, Cheavar A. Blair, Terry D. Hinds Jr.

Markey Cancer Center Faculty Publications

The insulin receptor (INSR) has been shown to be hyperactive in hepatic stellate cells (HSCs) in humans and rodents with liver fibrosis. To explore HSC cellular mechanisms that INSR regulates during pro-fibrotic stimulation, we used CRISPR-Cas9 technology. We knocked out a portion of the INSR gene in human LX2 HSC cells (INSRe5- 8 KO) that regulates insulin responsiveness but not the insulin-like growth factor (IGF) or transforming growth factor-β (TGFβ) signaling. The INSRe5- 8 KO HSCs had significantly higher cell growth, BrdU incorporation, and lower TP53 expression that suppresses growth, and they also exhibited increased migration compared to the Scramble …

Lc-Ms Analysis Of Serum Lipidomic And Metabolomic Signatures In Pediatric Patients With Acute Lymphoblastic Leukemia, Feiyu Yan, Shengnan Wang, Yilin Wang, Yan Sun, Jing Yang, Lirong Sun, Yekaterina Y. Zaytseva, Pan Deng, Lingzhen Wang

Markey Cancer Center Faculty Publications

Background Acute lymphoblastic leukemia (ALL) is a prevalent hematologic malignancy that primarily affects children. The diagnosis and treatment of pediatric ALL remain challenging. This study aimed to identify differential lipids and metabolites that may hold potential for improving ALL treatment.

Methods In this retrospective case-control study, serum samples obtained from children with ALL and healthy controls were analyzed. Serum lipidome and metabolome alterations of ALL were analyzed by comparing pediatric patients with ALL with healthy controls based on liquid chromatography high-resolution mass spectrometry analysis of serum lipidomic and metabolomic signatures.

Results We identified 2,298 lipid features in the serum. Among …

Exploring Oxylipins In Host–Microbe Interactions And Their Impact On Infection And Immunity, Robert J. Neff, Christopher D. Radka

Markey Cancer Center Faculty Publications

Plasma lipids are essential components of biological systems, transported through interactions with proteins to maintain cellular functions. These lipids exist in various forms, such as fatty acids, glycerolipids, glycerophospholipids, sphingolipids, sterols, and prenol lipids, derived from dietary intake, adipose tissue, and biosynthesis. While the association between certain fatty acids and cardiovascular diseases has been widely recognized, polyunsaturated fatty acids (PUFAs) exhibit cardioprotective effects, reducing risks of arrhythmias and heart-related mortality. This is due to their role in the production of eicosanoids, which modulate inflammation. Chronic inflammation, particularly in obesity, is significantly influenced by fatty acids, with saturated fatty acids promoting …

Predicting The Pathway Involvement Of Compounds Annotated In The Reactome Knowledgebase, Erik D. Huckvale, Hunter N. B. Moseley

Markey Cancer Center Faculty Publications

Background/Objectives: Pathway annotations of non-macromolecular (relatively small) biomolecules facilitate biological and biomedical interpretation of metabolomics datasets. However, low pathway annotation levels of detected biomolecules hinder this type of interpretation. Thus, predicting the pathway involvement of detected but unannotated biomolecules has a high potential to improve metabolomics data analysis and omics integration. Past publications have only made use of the Kyoto Encyclopedia of Genes and Genomes-derived datasets to develop machine learning models to predict pathway involvement. However, to our knowledge, the Reactome knowledgebase has not been utilized to develop these types of predictive models.

Methods: We created a dataset ready for …

Characterization, Performance, And Toxicological Assessment Of Polysulfone-Sulfonated Polyether Ether Ketone Membranes For Water Separation Applications, Muhammad Usman Yousaf, Lucca Madeo Cortarelli, Nerissa I. Jebet, Jason M. Unrine, Nirupam Aich, Olga V. Tsyusko, Isabel C. Escobar

Markey Cancer Center Faculty Publications

The removal of small molecular weight charged compounds from aqueous solutions using membrane remains a challenge. In this study, polysulfone (PSf)- and sulfonated polyether ether ketone (SPEEK)-based membranes were fabricated via non- solvent induced phase separation process (NIPS) using N-Methyl-2-Pyrrolidone (NMP) as solvent and water as non-solvent. Membranes were characterized structurally and morphologically, followed by toxicity assessment conducted before and after filtration, both with and without annealing at various pH values to evaluate potential leaching of trapped solvent from the membrane pores. Additionally, membrane performance was characterized using binary mixtures of cationic and anionic dyes. The results demonstrated selective filtration …

Computational Design And In Vitro And In Vivo Characterization Of An Apoe-Based Synthetic High-Density Lipoprotein For Sepsis Therapy, Ling Guo, Yaxia Yuan, Fang Zhang, Chang-Guo Zhan, Xiangan Li

Markey Cancer Center Faculty Publications

Introduction: Septic patients have low levels of high-density lipoproteins (HDLs), which is a risk factor. Replenishing HDLs with synthetic HDLs (sHDLs) has shown promise as a therapy for sepsis. This study aimed to develop a computational approach to design and test new types of sHDLs for sepsis treatment. Methods: We used a three-step computational approach to design sHDL nanoparticles based on the structure of HDLs and their binding to endotoxins. We tested the efficacy of these sHDLs in two sepsis mouse models—cecal ligation and puncture (CLP)-induced and P. aeruginosa-induced sepsis models—and assessed their impact on inflammatory signaling in cells. Results: …

Artesunate Enhances The Efficacy Of Enzalutamide In Advanced Prostate Cancer, Xinyi Wang, Jinghui Liu, Fengyi Mao, Yifan Kong, Qiongsi Zhang, Chaohao Li, Daheng He, Chi Wang, Yanquan Zhang, Ruixin Wang, Sally R. Ellingson, Qiou Wei, Zhiguo Li, Xiaoqi Liu

Markey Cancer Center Faculty Publications

Prostate cancer (PCa) is one of the leading causes of death among men worldwide. Treatments targeting the androgen receptor pathway remain the standard therapy for PCa patients. Enzalutamide (ENZ), a second-generation androgen receptor inhibitor, was developed to treat castration-resistant prostate cancer. However, while patients initially respond to ENZ, drug resistance typically develops within a few months. Artesunate (ART), a semisynthetic derivative of the Artemisinin plant, is approved for antimalaria treatment. In this study, we conducted an FDA-approved drug screening and identified ART as a potential candidate for overcoming ENZ resistance in PCa. Mechanistically, ART induces the degradation of c-Myc, enhancing …