Life Sciences Commons^™

Elucidating Immune-Related Gene Transcriptional Programs Via Factorization Of Large-Scale Rna-Profiles, Shan He, Matthew M Gubin, Hind Rafei, Rafet Basar, Merve Dede, Xianli Jiang, Qingnan Liang, Yukun Tan, Kunhee Kim, Maura L Gillison, Katayoun Rezvani, Weiyi Peng, Cara Haymaker, Sharia Hernandez, Luisa M Solis, Vakul Mohanty, Ken Chen

Faculty, Staff and Student Publications

Recent developments in immunotherapy, including immune checkpoint blockade (ICB) and adoptive cell therapy (ACT), have encountered challenges such as immune-related adverse events and resistance, especially in solid tumors. To advance the field, a deeper understanding of the molecular mechanisms behind treatment responses and resistance is essential. However, the lack of functionally characterized immune-related gene sets has limited data-driven immunological research. To address this gap, we adopted non-negative matrix factorization on 83 human bulk RNA sequencing (RNA-seq) datasets and constructed 28 immune-specific gene sets. After rigorous immunologist-led manual annotations and orthogonal validations across immunological contexts and functional omics data, we demonstrated …

The Role And Mechanism Of Cinnamaldehyde In Cancer, Jiahua Peng, Xin Song, Wenbin Yu, Yuhan Pan, Yufei Zhang, Hui Jian, Bin He

Journal of Food and Drug Analysis

As cancer continues to rise globally, there is growing interest in discovering novel methods for prevention and treatment. Due to the limitations of traditional cancer therapies, there has been a growing emphasis on investigating herbal remedies and exploring their potential synergistic effects when combined with chemotherapy drugs. Cinnamaldehyde, derived from cinnamon, has gained significant attention for its potential role in cancer prevention and treatment. Extensive research has demonstrated that cinnamaldehyde exhibits promising anticancer properties by modulating various cellular processes involved in tumor growth and progression. However, challenges and unanswered questions remain regarding the precise mechanisms for its effective use as …

Macrophage-Driven Car T Cell Resistance In B Cell Lymphoma, Sae Bom Lee

USF Tampa Graduate Theses and Dissertations

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of patients with relapsed/ refractory large B cell lymphoma (LBCL). Despite its promising efficacy, a subset of patients experiences primary resistance or relapse. In Chapter 2, we explore the tumor microenvironment (TME)-induced resistance mechanisms in patients with LBCL. Analysis of the intratumoral immune infiltrates in pre-infusion tumor biopsies revealed that the levels of immunoregulatory macrophages were elevated in patients who responded poorly to axicabtagene ciloleucel (axi-cel). Using preclinical mouse B cell tumor models, we found that the CAR T-cell-produced interferon-gamma (IFN-γ) enhanced the expression of inducible nitric oxide synthase (iNOS, …

Clinical Features And Genomic Epidemiology Of Bloodstream Infections Due To Enterococcal Species Other Than Enterococcus Faecalis Or E Faecium In Patients With Cancer, Dierdre B Axell-House, Patrycja A Ashley, Stephanie L Egge, Truc T Tran, Claudia Pedroza, Meng Zhang, An Q Dinh, Shelby R Simar, Pranoti V Sahasrabhojane, William R Miller, Samuel A Shelburne, Blake M Hanson, Cesar A Arias

Faculty, Staff and Student Publications

BACKGROUND: Non–Enterococcus faecium, non–E. faecalis (NFF) enterococci are a heterogeneous group of clinically pathogenic enterococci that include species with intrinsic low-level vancomycin resistance. Patients with cancer are at increased risk for bacteremia with NFF enterococci, but their clinical and molecular epidemiology have not been extensively described.

METHODS: We conducted a retrospective review of all patients (n = 70) with NFF bacteremia from 2016 to 2022 at a major cancer center. The main outcomes assessed were 30-day mortality, microbiological failure (positive blood cultures for ≥4 days), and recurrence of bacteremia (positive blood cultureclearance). Whole-genome sequencing was performed on all …

Glutaminase - A Potential Target For Cancer Treatment, Josephine Anthony, Sureka Varalakshmi, Ashok Kumar Sekar, Nalini Devarajan, Balamurugan Janakiraman, Rajendran Peramaiyan

BioMedicine

The overexpression of glutaminase is reported to influence cancer growth and metastasis through glutaminolysis. Upregulation of glutamine catabolism is recently recognized as a critical feature of cancer, and cancer cells are observed to reprogram glutamine metabolism to maintain its survival and proliferation. Special focus is given on the glutaminase isoform, GLS1 (kidney type glutaminase), as the other isoform GLS2 (Liver type glutaminase) acts as a tumour suppressor in some conditions. Glutaminolysis linked with autophagy, which is mediated via mTORC1, also serves as a promising target for cancer therapy. Glutamine also plays a vital role in maintaining redox homeostasis. Inhibition of …

Using Rapid Protein Degradation To Determine The Effect Of Runx1 Loss-Of- Function On Dna Damage Accumulation And Repair., Jackriel Pina Morales

Theses and Dissertations

Germline mutations in RUNX1 are associated with familial platelet disorder with a predisposition to myeloid malignancy (RUNX1-FPDMM), in which patients present with low platelet counts,excessive bleeding and bruising, and an increased risk of Acute Myeloid Leukemia (AML)/Myelodysplastic Syndrome (MDS) development throughout their lifetime. To understand how these loss-of-function mutations in RUNX1 drive predispose to malignancy, it is important to develop a detailed understanding of the molecular basis of RUNX1 function. While RUNX1 is a transcription factor, preliminary data from our group and work from others suggests that RUNX1 also interacts with proteins that are critical for DNA damage …

A Gold Standard-Derived Modular Barcoding Approach To Cancer Transcriptomics, Yan Zhu, Mohamad Karim I Koleilat, Jason Roszik, Man Kam Kwong, Zhonglin Wang, Dipen M Maru, Scott Kopetz, Lawrence N Kwong

Faculty, Staff and Student Publications

A challenge with studying cancer transcriptomes is in distilling the wealth of information down into manageable portions of information. In this resource, we develop an approach that creates and assembles cancer type-specific gene expression modules into flexible barcodes, allowing for adaptation to a wide variety of uses. Specifically, we propose that modules derived organically from high-quality gold standards such as The Cancer Genome Atlas (TCGA) can accurately capture and describe functionally related genes that are relevant to specific cancer types. We show that such modules can: (1) uncover novel gene relationships and nominate new functional memberships, (2) improve and speed …

Identifying Novel Upstream Regulators Of The Hippo Pathway: Forward Genetic Screen In Drosophila Melanogaster, Akshara Iyer

Honors Scholar Theses

The Hippo pathway is an evolutionarily conserved developmental pathway that controls organ size and tissue homeostasis in all metazoan animals. Dysregulated Hippo pathway has been implicated in a wide range of human disorders, including cancer. The physiological function of the Hippo pathway is best understood in Drosophila, where inactivation of the Hippo pathway tumor suppressors, or overexpression of the Yorkie (Yki) oncoprotein, results in tissue overgrowth characterized by excessive cell proliferation and diminished apoptosis, and increased transcription of Hippo pathway target genes such as diap1 and expanded (ex). Despite the well-established Hippo pathway core signaling cascade, the upstream regulation of …

Assessment Of In-Vitro And In-Vivo Pre-Clinical Pharmacokinetics Of Epz015666; A Novel Small Molecule For Medulloblastoma Treatment, Pratiksha U. Kshirsagar

Theses & Dissertations

Group 3 medulloblastoma (MB) has the worst prognosis of the MB subgroups associated with elevated MYC expression and a 5-year survival rate of

Quantitation of EPZ was performed on a Shimadzu LC-MS/MS system utilizing electrospray ionization operated in positive mode. The validated assay was linear from 0.2 to 500 ng/mL. Metabolic stability studies demonstrated slow intrinsic clearance of EPZ in mouse and human liver microsomes, suggesting no CYP-mediated metabolism. Additionally, EPZ exhibited low binding affinity to plasma and brain proteins and high apparent permeability across artificial membranes, indicating efficient membrane penetration. Drug transporter studies identified EPZ as a substrate of …

Genetic Variants For Head Size Share Genes And Pathways With Cancer, Maria J Knol, Raymond A Poot, Tavia E Evans, Claudia L Satizabal, Aniket Mishra, Muralidharan Sargurupremraj, Sandra Van Der Auwera, Marie-Gabrielle Duperron, Xueqiu Jian, Isabel C Hostettler, Dianne H K Van Dam-Nolen, Sander Lamballais, Mikolaj A Pawlak, Cora E Lewis, Amaia Carrion-Castillo, Theo G M Van Erp, Céline S Reinbold, Jean Shin, Markus Scholz, Asta K Håberg, Anders Kämpe, Gloria H Y Li, Reut Avinun, Joshua R Atkins, Fang-Chi Hsu, Alyssa R Amod, Max Lam, Ami Tsuchida, Mariël W A Teunissen, Nil Aygün, Yash Patel, Dan Liang, Alexa S Beiser, Frauke Beyer, Joshua C Bis, Daniel Bos, R Nick Bryan, Robin Bülow, Svenja Caspers, Gwenaëlle Catheline, Charlotte A M Cecil, Shareefa Dalvie, Jean-François Dartigues, Charles Decarli, Maria Enlund-Cerullo, Judith M Ford, Barbara Franke, Barry I Freedman, Nele Friedrich, Melissa J Green, Simon Haworth, Catherine Helmer, Per Hoffmann, Georg Homuth, M Kamran Ikram, Clifford R Jack, Neda Jahanshad, Christiane Jockwitz, Yoichiro Kamatani, Annchen R Knodt, Shuo Li, Keane Lim, W T Longstreth, Fabio Macciardi, Outi Mäkitie, Bernard Mazoyer, Sarah E Medland, Susumu Miyamoto, Susanne Moebus, Thomas H Mosley, Ryan Muetzel, Thomas W Mühleisen, Manabu Nagata, Soichiro Nakahara, Nicholette D Palmer, Zdenka Pausova, Adrian Preda, Yann Quidé, William R Reay, Gennady V Roshchupkin, Reinhold Schmidt, Pamela J Schreiner, Kazuya Setoh, Chin Yang Shapland, Stephen Sidney, Beate St Pourcain, Jason L Stein, Yasuharu Tabara, Alexander Teumer, Anne Uhlmann, Aad Van Der Lugt, Meike W Vernooij, David J Werring, B Gwen Windham, A Veronica Witte, Katharina Wittfeld, Qiong Yang, Kazumichi Yoshida, Han G Brunner, Quentin Le Grand, Kang Sim, Dan J Stein, Donald W Bowden, Murray J Cairns, Ahmad R Hariri, Ching-Lung Cheung, Sture Andersson, Arno Villringer, Tomas Paus, Sven Cichon, Vince D Calhoun, Fabrice Crivello, Lenore J Launer, Tonya White, Peter J Koudstaal, Henry Houlden, Myriam Fornage, Fumihiko Matsuda, Hans J Grabe, M Arfan Ikram, Stéphanie Debette, Paul M Thompson, Sudha Seshadri, Hieab H H Adams

Faculty, Staff and Student Publications

The size of the human head is highly heritable, but genetic drivers of its variation within the general population remain unmapped. We perform a genome-wide association study on head size (N = 80,890) and identify 67 genetic loci, of which 50 are novel. Neuroimaging studies show that 17 variants affect specific brain areas, but most have widespread effects. Gene set enrichment is observed for various cancers and the p53, Wnt, and ErbB signaling pathways. Genes harboring lead variants are enriched for macrocephaly syndrome genes (37-fold) and high-fidelity cancer genes (9-fold), which is not seen for human height variants. Head size …

Fam86a Methylation Of Eef2 Links Mrna Translation Elongation To Tumorigenesis, Joel William Francis, Simone Hausmann, Sabeen Ikram, Kunlun Yin, Robert Mealey-Farr, Natasha Mahealani Flores, Annie Truc Trinh, Tourkian Chasan, Julia Thompson, Pawel Karol Mazur, Or Gozani

Faculty, Staff and Student Publications

eEF2 post-translational modifications (PTMs) can profoundly affect mRNA translation dynamics. However, the physiologic function of eEF2K525 trimethylation (eEF2K525me3), a PTM catalyzed by the enzyme FAM86A, is unknown. Here, we find that FAM86A methylation of eEF2 regulates nascent elongation to promote protein synthesis and lung adenocarcinoma (LUAD) pathogenesis. The principal physiologic substrate of FAM86A is eEF2, with K525me3 modeled to facilitate productive eEF2-ribosome engagement during translocation. FAM86A depletion in LUAD cells causes 80S monosome accumulation and mRNA translation inhibition. FAM86A is overexpressed in LUAD and eEF2K525me3 levels increase through advancing LUAD disease stages. FAM86A knockdown attenuates LUAD cell proliferation and suppression …

Bcl2 Mediated Targeted Drug Delivery For The Treatment Of Kidney Fibrosis And Stomach Cancer, Humayra Afrin

Open Access Theses & Dissertations

Apoptosis, the programmed death of cells, is primarily regulated by a delicate balance between pro-apoptotic and anti-apoptotic signals. The Bcl-2 (B-cell lymphoma 2) family of proteins acts as anti-apoptotic agents, promoting cell survival. Dysregulation of these proteins is a common occurrence in conditions such as cancer and fibrosis, where overexpression of anti-apoptotic members can foster tumor cell survival and fibroblast activation. In this study, our aim was to explore the therapeutic potential of Bcl-2 inhibitors, both as a small molecule (specifically Navitoclax (Navi)), inhibitor and as Bcl-2 siRNA, for targeted treatment. Intravenous administration of Navi often leads to thrombocytopenia, necessitating …

Mapping Recommendations Towards An Asian Code Against Cancer (Acac) As Part Of The World Code Against Cancer Framework: An Asian National Cancer Centers Alliance (Ancca) Initiative, Sok King Ong, Sarah K Abe, Gillian Li Gek Phua, Harindra Jayasekara, Kayo Togawa, Laureline Gatellier, Jeongseon Kim, Yawei Zhang, Siti Zuhrini Kahan, Siti Norbayah Yusof, Jong Soo Han, C S Pramesh, Manju Sengar, Abhishek Shankar, Clarito Cairo, Suleeporn Sangrajran, Erdenekhuu Nansalmaa, Tseveen Badamsuren, Tashi Dendup, Kinley Tshering, Jie He, R Soeko Werdi Nindito D, Azmi Ritana, Jeong Soo Im, Eun Young Park, Giang Nguyen Huong, Tran Thi Thanh Huong, Mohammed Biglari, Aasim Yusuf, Kishore Kumar Pradhananga, Champadeng Vongdala, Muhammad Taufiq Bin Jaafar, Nor Saleha Ibrahim Tamin, Yi Yi Myint, Kyaw Kan Kaung, Md Shafiur Rahman, Eshani Fernando, Beauta Rath, Babu Sukumaran, William Yk Hwang, Carolina Espina, Joachim Schüz, Manami Inoue, Tomohiro Matsuda

Faculty, Staff and Student Publications

This paper outlines the process undertaken by Asian National Cancer Centers Alliance (ANCCA) members in working towards an Asian Code Against Cancer (ACAC). The process involves: (i) identification of the criteria for selecting the existing set of national recommendations for ACAC (ii) compilation of existing national codes or recommendations on cancer prevention (iii) reviewing the scientific evidence on cancer risk factors in Asia and (iv) establishment of one or more ACAC under the World Code Against Cancer Framework. A matrix of national codes or key recommendations against cancer in ANCCA member countries is presented. These include taking actions to prevent …

Screening Of Orthodontic Patients And Age-Matched Non- Orthodontic Samples For High-Risk Oncogenic Human Papillomavirus (Hpv) Strains, Hunter Hinton

UNLV Theses, Dissertations, Professional Papers, and Capstones

Introduction: The human papillomavirus (HPV) is known to cause cancer in several tissues and organs, including the cervix and the oral cavity. Several oncogenic or high-risk strains have been identified, which include HPV16 and HPV18.However, other research has demonstrated that additional oncogenic, high-risk strains exist - including HPV31, HPV33, HPV35, HPV52 and HPV58, although much less is known about their prevalence. Based upon this lack of knowledge, the primary objective of this project is to address the prevalence of these strains among pediatric and adult patients through screening of saliva samples from the UNLV-SDM and orthodontic clinic populations.

Methods: The …

Intermittent Fasting And Its Impact On Toxicities, Symptoms And Quality Of Life In Patients On Active Cancer Treatment, Robert Li Sucholeiki, Casey L Propst, David S Hong, Goldy C George

Faculty, Staff and Student Publications

Intermittent fasting is a dietary intervention that is increasingly being tested for positive outcomes in patients receiving cancer treatment. In this review, we examine the impact of intermittent fasting on symptoms, toxicities, and quality of life in patients undergoing cancer therapy and highlight unmet investigative areas to prompt future research. While current evidence is preliminary and conclusions mixed, some promising clinical studies suggest that intermittent fasting interventions may improve fatigue and reduce gastrointestinal toxicities in certain patients with cancer. Emerging clinical evidence also demonstrates that intermittent fasting may reduce off-target DNA damage, and induce favorable cellular-level immune remodeling. Furthermore, intermittent …

A Novel Algorithm For The Virtual Screening Of Extensive Small Molecule Libraries Against Ercc1/Xpf Protein-Protein Interaction For The Identification Of Therapeutic Resistance-Bypassing Small Anticancer Molecules, Salma Ghazy, Lalehan Oktay, Serdar Durdagi

Turkish Journal of Biology

Background and aim:Cancer cell’s innate chemotherapeutic resistance continues to be an obstacle in molecular oncology. This theory is firmly tied to the cancer cells’ integral DNA repair mechanisms continuously neutralizing the effects of chemotherapy. Amidst these mechanisms, the nuclear excision repair pathway is crucial in renovating DNA lesions prompted by agents like Cisplatin. The ERCC1/XPF complex stands center-stage as a structure specific endonuclease in this repair pathway. Targeting the ERCC1/XPF dimerization brings forth a strategy to augment chemotherapy by eschewing the resistance mechanism integral to cancer cells. This study tracks and identifies small anticancer molecules, with ERCC1/XPF inhibiting potential, within …

Cocoa Polyphenols Modulate The Fecal Microbiome In A Mouse Model Of Colitis, Independent Of Basal Diet And Colon Inflammation, Abby D. Benninghoff

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Chronic inflammation increases the risk of developing multiple chronic diseases, including cancer. The risk of developing colorectal cancer (CRC) specifically is increased in individuals who suffer from colitis, a characteristic of Inflammatory Bowel Disease (IBD). Diet is another risk factor for developing CRC, particularly an inflammation-promoting Western-type diet. Thus, supplementing a Western diet with functional foods containing anti-inflammatory polyphenols is a potential approach to decreasing CRC risk by reducing gut inflammation and altering gut microbiome profile. This study aimed to determine the effects of cocoa polyphenol (CP) supplementation on inflammation status and microbiome profile before, during, and after colitis when …

Gut Microbial Dysbiosis Differs In Two Distinct Cachectic Tumor-Bearing Models Consuming The Same Diet, Lauri O. Byerley, Brittany Lorenzen, Hsiao Man Chang, William G. Hartman, Michael J. Keenan, Ryan Page, Meng Luo, Scot E. Dowd, Christopher M. Taylor

School of Medicine Faculty Publications

The impact of cancer cachexia on the colonic microbiota is poorly characterized. This study assessed the effect of two cachectic-producing tumor types on the gut microbiota to determine if a similar dysbiosis could be found. In addition, it was determined if a diet containing an immunonutrient-rich food (walnuts) known to promote the growth of probiotic bacteria in the colon could alter the dysbiosis and slow cachexia. Male Fisher 344 rats were randomly assigned to a semi-purified diet with or without walnuts. Then, within each diet group, rats were further assigned randomly to a treatment group: tumor-bearing ad libitum fed (TB), …

Enhanced Plant-Derived Vesicles For Nucleotide Delivery For Cancer Therapy, Sara Corvigno, Yuan Liu, Emine Bayraktar, Elaine Stur, Nazende Nur Bayram, Adrian Lankenau Ahumada, Supriya Nagaraju, Cristian Rodriguez-Aguayo, Hu Chen, Thanh Chung Vu, Yunfei Wen, Han Liang, Li Zhao, Sanghoon Lee, Gabriel Lopez-Berestein, Anil K Sood

Faculty, Staff and Student Publications

Small RNAs (microRNAs [miRNAs] or small interfering RNAs [siRNAs]) are effective tools for cancer therapy, but many of the existing carriers for their delivery are limited by low bioavailability, insufficient loading, impaired transport across biological barriers, and low delivery into the tumor microenvironment. Extracellular vesicle (EV)-based communication in mammalian and plant systems is important for many physiological and pathological processes, and EVs show promise as carriers for RNA interference molecules. However, some fundamental issues limit their use, such as insufficient cargo loading and low potential for scaling production. Plant-derived vesicles (PDVs) are membrane-coated vesicles released in the apoplastic fluid of …

Oncolytic Adenoviruses And Immunopeptidomics: A Convenient Marriage, Marc Garcia-Moure, Andrew G Gillard, Marta M Alonso, Juan Fueyo, Candelaria Gomez-Manzano

Faculty, Staff and Student Publications

Oncolytic viruses (OVs) are biological therapeutic agents that selectively destroy cancer cells while sparing normal healthy cells. Besides direct oncolysis, OV infection induces a proinflammatory shift in the tumor microenvironment and the release of tumor-associated antigens (TAAs) that might induce an anti-tumor immunity. Due to their immunostimulatory effect, OVs have been explored for cancer vaccination against specific TAAs. However, this approach usually requires genetic modification of the virus and the production of a new viral vector for each target, which is difficult to implement for low prevalent antigens. In a recent study, Chiaro et al. presented an elegant proof of …

Jaspine B And The Sea Sponge That Fights Cancer, Jack Davis, Jared Barrott, Adriene Pavek, Farjana Afrin, Sameena Mateen, Brendon Meldrum, Rocio Rojas, Pamela Diaz, Megan Condie, Ali Aghazadeh-Habashi, Srinath Pashikanti

Library/Life Sciences Undergraduate Poster Competition 2024

Jaspine B is a natural marine product, derived from the sea sponge, Jaspis, found in some tropical climates. Jaspine B has been shown to be an effective treatment in some cancers with an upregulation of sphingomyelin synthase. This research aimed to understand the effects of Jaspine B on synovial sarcoma, and investigate its potential to be used as targeted treatment in other cancers that have an upregulation of sphingomyelin synthase

The Cold Hard Truth: Cryopreserved Tissue Is Superior To Ffpe Tissue In Molecular Analysis, Delaney Anderson, Jeffrey Okojie, Mackenzie Burr, Peyton Worley, Isaac Parker, Jack Davis, Bridger Kearns, Jared Barrott

Library/Life Sciences Undergraduate Poster Competition 2024

Personalized cancer care requires molecular characterization of neoplasms. While the research community accepts frozen tissues as the gold standard analyte for molecular assays, the source of tissue for all testing of tumor tissue in clinical cancer care comes almost universally from formalin-fixed, paraffin-embedded tissue (FFPE). Specific to genomics assays, numerous studies have shown significant discordance in genetic information obtained from FFPE samples and cryopreserved or flash frozen samples. To explain the discordance between FFPE samples and cryopreserved samples, a head-to-head comparison between FFPE and cryopreserved tissues was performed to analyze the DNA yield, DNA purity and DNA quality in terms …

The Changing Tumor Microenvironment Of Non-Small Cell Lung Cancer, Mackenzie Hansen, Kim O'Neill, Qin Zhou, Yoko Derose, Magdalena Kovacsovics, Benjamin Brintz, Benjamin L. Witt, Siwen Hu-Lieskovan

Library/Life Sciences Undergraduate Poster Competition 2024

Lung cancer is the leading cause of cancer related death in the United States, and non-small cell (NSCLC) is the most common type. An increasingly prevalent treatment in the last few years for NSCLC has been immunotherapy. However, for immunotherapy to be the most effective, we need to have a better understanding of how the immune system interacts with cancer in all stages. Specifically, we need to know where the immune cells reside, how they interact with each other, and how these populations change as the disease progresses. To define the tumor microenvironment, we stained 27 whole tumor slides with …

Targeting Hsp90: A Novel Approach To Combat Synovial Sarcomas, Peyton Worley, Jared Barrott, Matt Kirkham, Drake Heithoff

Library/Life Sciences Undergraduate Poster Competition 2024

Synovial sarcomas are rare muscle cancers that have very few targeted therapies. HSP90 is a protein upregulated in this form of cancer and many others. A screening of this cancer was done in vitro, using FDA-approved drugs, showing that HSP90 could be a promising treatment option. A novel HSP90 inhibitor was applied to human and mouse synovial sarcoma cell lines and was analyzed after receiving a drug treatment for HSP90.

Downregulation Of Irf8 In Alveolar Macrophages By G-Csf Promotes Metastatic Tumor Progression, Stephanie L Tzetzo, Elliot D Kramer, Hemn Mohammadpour, Minhyung Kim, Spencer R Rosario, Han Yu, Melissa R Dolan, Chetan C Oturkar, Brian G Morreale, Paul N Bogner, Aimee B Stablewski, Fernando J Benavides, Craig M Brackett, John M L Ebos, Gokul M Das, Mateusz Opyrchal, Michael J Nemeth, Sharon S Evans, Scott I Abrams

Faculty, Staff and Student Publications

Tissue-resident macrophages (TRMs) are abundant immune cells within pre-metastatic sites, yet their functional contributions to metastasis remain incompletely understood. Here, we show that alveolar macrophages (AMs), the main TRMs of the lung, are susceptible to downregulation of the immune stimulatory transcription factor IRF8, impairing anti-metastatic activity in models of metastatic breast cancer. G-CSF is a key tumor-associated factor (TAF) that acts upon AMs to reduce IRF8 levels and facilitate metastasis. Translational relevance of IRF8 downregulation was observed among macrophage precursors in breast cancer and a

Viral Epitope Scanning Reveals Correlation Between Seasonal Hcovs And Sars-Cov-2 Antibody Responses Among Cancer And Non-Cancer Patients, Salum J. Lidenge, Dicle Yalcin, Sydney J. Bennett, Owen Ngalamika, Brenda B. Kweyamba, Chacha J. Mwita, For Yue Tso, Julius Mwaiselage, John T. West, Charles Wood

School of Biological Sciences: Faculty Publications

Seasonal coronaviruses (HCoVs) are known to contribute to cross-reactive antibody (Ab) responses against SARS-CoV-2. While these responses are predictable due to the high homology between SARS-CoV-2 and other CoVs, the impact of these responses on susceptibility to SARS-CoV-2 infection in cancer patients is unclear. To investigate the influence of prior HCoV infection on anti- SARS-CoV-2 Ab responses among COVID-19 asymptomatic individuals with cancer and controls without cancers, we utilized the VirScan technology in which phage immunoprecipitation and sequencing (PhIP-seq) of longitudinal plasma samples was performed to investigate high-resolution (i.e., epitope level) humoral CoV responses. Despite testing positive for anti-SARS-CoV-2 Ab …

The Fatigue-Inducing Effects Of Cancer And Its Therapy Are Characterized By Decreased Physical Activity In The Absence Of Any Motivational Deficit, Thien T Phan, Kiersten S Scott, Brandon Chelette, A Phillip West, Robert Dantzer

Faculty, Staff and Student Publications

Although cancer and its therapy are well known to be associated with fatigue, the exact nature of cancer-related fatigue remains ill-defined. We previously reported that fatigue-like behavior induced independently by tumor growth and by the chemotherapeutic agent cisplatin is characterized by reduced voluntary wheel running and an intact motivation to expand effort for food rewards. The present set of experiments was initiated to characterize the functional consequences of fatigue induced by chemoradiotherapy in tumor-bearing mice and relate them to changes in the expression of genes coding for inflammation, mitochondria dynamics and metabolism. Two syngeneic murine models of cancer were selected …

Peroxisome Proliferator-Activated Receptors As Therapeutic Target For Cancer, Yuqing Wang, Feifei Lei, Yiyun Lin, Yuru Han, Lei Yang, Huabing Tan

Faculty, Staff and Student Publications

Peroxisome proliferator-activated receptors (PPARs) are transcription factors belonging to the nuclear receptor family. There are three subtypes of PPARs, including PPAR-α, PPAR-β/δ and PPAR-γ. They are expressed in different tissues and act by regulating the expression of target genes in the form of binding to ligands. Various subtypes of PPAR have been shown to have significant roles in a wide range of biological processes including lipid metabolism, body energy homeostasis, cell proliferation and differentiation, bone formation, tissue repair and remodelling. Recent studies have found that PPARs are closely related to tumours. They are involved in cancer cell growth, angiogenesis and …

Cardiovascular Events After Cancer Immunotherapy As Oncologic Emergencies: Analyses Of 610 Head And Neck Cancer Patients Treated With Immune Checkpoint Inhibitors, Cielito C Reyes-Gibby, Aiham Qdaisat, Renata Ferrarotto, Anecita Fadol, Jason J Bischof, Christopher J Coyne, Demis N Lipe, Ehab Y Hanna, Sanjay Shete, Jun-Ichi Abe, Sai-Ching J Yeung

Faculty, Staff and Student Publications

Background: Cardio-oncology and emergency medicine are closely collaborative, as many cardiac events in cancer patients require evaluation and treatment in the emergency department (ED). Immune checkpoint inhibitors (ICIs) have become a common treatment for patients with head and neck cancer (HNC). However, the immune-related adverse events (irAEs) from ICIs can be clinically significant.

Methods: We reviewed and analyzed cardiovascular diagnoses among HNC patients who received ICI during the period April 1, 2016-December 31, 2020 in a large tertiary cancer center. Demographics, clinical and cancer-related data were abstracted, and billing databases were queried for cardiovascular disease (CVD)-related diagnosis using International Classification …

Patients With Advanced Cancer And Their Spouses Parenting Minor Children: The Role Of The Relationship Context In Parenting Concerns, Kathrin Milbury, Sujin Ann-Yi, Morgan Jones, Yisheng Li, Meagan Whisenant, Sania Yousuf, Victoria Necroto, Mariana Chavez Mac Gregor, Eduardo Bruera

Faculty, Staff and Student Publications

Objective: Patients with advanced cancer who parent minor children report parenting concerns and increased psychological distress. This cross-sectional study seeks to understand parenting-related issues in patients and spousal caregivers from a relationship perspective.

Methods: Patients with a metastatic solid malignancy and their spouses independently completed cross-sectional assessments of psychological distress (Hospital Anxiety and Depression Scale), parenting concerns (Parenting Concern Questionnaire) and efficacy (Cancer-Related Parenting Self-Efficacy Scale), and relationship measures (DAS-7, Couples' Illness Communication Scale, and Family Relationship Index).

Results: Of the 51 patients (57% female, 49% NHW, mean age 42 years) and spouses (43% female, 43% NHW, mean age of …