Digital Commons Network^™

Antagomir Treatment For Deep-Space Simulated Changes In The Liver Of Mice, Natalie P. Hayslip

Honors Undergraduate Theses

With the start of NASA’s Artemis program, astronauts will soon leave the protection of Earth’s magnetosphere. Previous studies have established a theme of liver dysregulation associated with the harmful radiation and microgravity experienced in deep space. MicroRNAs (miRNAs) are key regulators of many of the pathologies observed during and after spaceflight, including hepatic fibrosis, making them strong potential biomarkers and therapeutic targets. Therefore, in the present study we investigated the effects of simulated microgravity, galactic cosmic radiation (GCR), and solar particle events (SPE) on miRNAs and mRNAs involved in the TGF-β signaling pathway, a key regulator of fibrosis, senescence, and …

Understanding Guardian Perceptions Of Whole-Foods Plant-Based Diets As Interventions In Pediatric Medicine, Vijay R. Luthra

Honors Undergraduate Theses

The obesity epidemic is widespread in American society, often affecting children who bear its consequences innocently. Due to a lack of nutrition knowledge, children rely on caregivers to meet their nutritional needs and instill healthy habits. This study examines parents' attitudes, knowledge, and behaviors, as well as perceived barriers to adopting a whole-foods plant-based diet (WFPD) for their children. Using a modified survey instrument by Morton et al., this study focused on parents and children regarding dietary choices. Participants were recruited from the waiting area of a pediatric clinic at the Medical College of Georgia between April and May 2023. …

The Impact Of Gestational Diabetes Mellitus And Maternal Oral Microbiome: A Scoping Review, Jaclyn P. Langan

Honors Undergraduate Theses

Background: Gestational diabetes mellitus (GDM) is a common pregnancy-related metabolic disorder associated with adverse maternal and fetal outcomes. Recent research has highlighted the potential role of the oral microbiome in the pathophysiology of various systemic conditions, including diabetes mellitus. However, the impact of GDM on the maternal oral microbiome remains relatively understudied. Understanding alterations in the oral microbiome during pregnancy complicated by GDM could provide valuable insights into the mechanistic links between systemic metabolic disorders and oral health.

Objective: The objective of this scoping review was to comprehensively examine the existing literature on the relationship between GDM and maternal oral …

How Hormonal Contraceptives Influence Injury In Female Athletes: A Systematic Review, Ashley V. Malvita

Honors Undergraduate Theses

Research indicates that female athletes have a higher risk of musculoskeletal injuries. Hormone fluctuations throughout the different periods of the menstruation cycle impacts the risk of injuries for women. Contraceptive use, most used in the form of an oral contraceptive pill, directly effects hormones and menstrual cycle related symptoms, with evidence of ameliorating some symptoms. Oral contraceptive use is suggested to influence musculoskeletal injuries in female athletes. However, there is little research and data that explores the direct relationship between oral contraceptive use and the injury rates of female athletes. Within this systematic review, five articles investigating this relationship fulfilled …

Investigating The Association Of Demographic Factors On Methotrexate Delay-Clearance And Toxicity In Pediatric Oncology Patients: A Retrospective Chart Review, Belal Alabdul Razzak

Honors Undergraduate Theses

High-dose methotrexate (HD MTX) is critical for treating pediatric malignancies such as acute lymphoblastic leukemia and neuro-carcinoma. However, its significant toxicity due to drug accumulation poses substantial risks. This retrospective study assesses the impact of demographic factors on MTX toxicity and clearance in pediatric oncology patients. Patient records from Saint Mary Hospital were analyzed, focusing on two MTX administration protocols: a 24-hour infusion followed by alkaline hydration and a 4-hour infusion followed by alkaline hydration. We hypothesize that factors such as age, body surface area (BSA), and body mass index (BMI) are associated with MTX clearance and toxicity. The study …

Co-Occurrence Of Autism Spectrum Disorder And Attention-Deficit/Hyperactivity Disorder With Idiopathic Hypersomnia: Data From The Hypersomnia Foundation Registry, Sophie Sevan Mikkelsen

Honors Undergraduate Theses

In recent years, hypersomnia patients and researchers alike have increasingly discussed the possibility of heightened comorbidities, or co-occurrences, of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) with the central disorders of hypersomnolence: idiopathic hypersomnia (IH) and narcolepsy (N). While a few scarce studies have investigated a link between ADHD and N, there has been no research on the co-occurrence of these conditions with IH. This study, using data from the Hypersomnia Foundation’s CoRDS Patient Registry, is the first to identify self-reported rates of ASD and ADHD diagnoses by people with idiopathic hypersomnia. Four chi-square tests were conducted to determine …

Assessment Of Forensic And Clinical Criteria Of Orbital Blowout Fractures For Use In Bioarchaeological Analysis, Dylan E. Ornot

Honors Undergraduate Theses

Orbital blowout fractures are a particular facial fracture occurring within the inner eye orbits of the face caused by blunt force trauma to the eyeball or the lower orbital rim. This fracture is common in modern clinical contexts due to physical assaults, but examining this fracture in skeletal material can also provide insights into the patterns of interpersonal violence within the fields of bioarchaeology and forensic anthropology. Issues with analyzing this fracture in skeletal material arise due to the clinical assessment practices of blowout fractures, where medical practitioners are highly focused on the soft tissue presentations of the fracture in …

Role Of Wave3 As An Actin Binding Protein In The Pathology Of Triple Negative Breast Cancer, Lamyae El Khalki, Khalid Sossey-Alaoui

Faculty Scholarship

Breast cancer, a prevalent global health concern, has sparked extensive research efforts, particularly focusing on triple negative breast cancer (TNBC), a subtype lacking estrogen receptor (ER), progesterone receptor, and epidermal growth factor receptor. TNBC's aggressive nature and resistance to hormone-based therapies heightens the risk of tumor progression and recurrence. Actin-binding proteins, specifically WAVE3 from the Wiskott–Aldrich syndrome protein (WASP) family, have emerged as major drivers in understanding TNBC biology. This review delves into the intricate molecular makeup of TNBC, shedding light on actin's fundamental role in cellular processes. Actin, a structural element in the cytoskeleton, regulates various cellular pathways essential …

The Cancer-Associated Secretory Phenotype: A New Frontier In Targeted Therapeutics, Xiaochao Tan, Guan-Yu Xiao, Priyam Banerjee, Shike Wang, Jonathan M. Kurie

Markey Cancer Center Faculty Publications

Oncogenic mutations activate secretory programs that drive tumor progression and represent therapeutic targets. The clinical relevance of CASPs is underscored by their prevalence, their linkages to specific genetic and epigenetic contexts, the proven efficacy of secretory blockade in preclinical models, and the availability of assays to identify vulnerable patient populations.

Carfilzomib-Loaded Ternary Polypeptide Nanoparticles Stabilized By Polycationic Complexation, Preye Mike Agbana, Ji Eun Park, Piotr G. Rychahou, Kyung-Bo Kim, Younsoo Bae

Markey Cancer Center Faculty Publications

Carfilzomib (CFZ) is a second-generation proteasome inhibitor showing great efficacy in multiple myeloma treatment, yet its clinical applications for other diseases such as solid cancers are limited due to low aqueous solubility and poor biostability. Ternary polypeptide nanoparticles (tPNPs) are drug carriers that we previ- ously reported to overcome these pharmaceutical limitations by entrapping CFZ in the core of the nanopar- ticles and protecting the drugs from degradation in biological media. However, preclinical studies revealed that tPNPs would require further improvement in particle stability to suppress initial burst drug release and thus achieve prolonged inhibition of proteasome activity with CFZ …

Cd8+ T Cell Metabolic Flexibility Elicited By Cd28-Ars2 Axis- Driven Alternative Splicing Of Pkm Supports Antitumor Immunity, G. Aaron Holling, Colin A. Chavel, Anand P. Sharda, Mackenzie M. Lieberman, Caitlin M. James, Shivana M. Lightman, Jason H. Tong, Guanxi Qiao, Tiffany R. Emmons, Thejaswini Giridharan, Shengqi Hou, Andrew M. Intlekofer, Richard M. Higashi, Teresa W. M. Fan, Andrew N. Lane, Kevin H. Eng, Brahm H. Segal, Elizabeth A. Repasky, Kevin P. Lee, Scott H. Olejniczak

Markey Cancer Center Faculty Publications

Metabolic flexibility has emerged as a critical determinant of CD8+ T-cell antitumor activity, yet the mechanisms driving the metabolic flexibility of T cells have not been determined. In this study, we investigated the influence of the nuclear cap-binding complex (CBC) adaptor protein ARS2 on mature T cells. In doing so, we discovered a novel signaling axis that endows activated CD8+ T cells with flexibility of glucose catabolism. ARS2 upregulation driven by CD28 signaling reinforced splicing factor recruitment to pre-mRNAs and affected approximately one-third of T-cell activation-induced alternative splicing events. Among these effects, the CD28-ARS2 axis suppressed the expression of the …

Abnormal Regulation Of Mitochondrial Sphingolipids During Aging And Alzheimer’S Disease, Simone M. Crivelli, Zainuddin Quadri, Ahmed Elsherbini, Hemendra J. Vekaria, Patrick G. Sullivan, Wenbo Zhi, Pilar Martinez-Martinez, Stefka D. Spassieva, Erhard Bieberich

Markey Cancer Center Faculty Publications

During pathogenesis of Alzheimer’s disease (AD), mitochondria suffer alterations that lead to low energy production and reactive oxygen species formation. However, the mechanism of impaired mitochondria homeostasis in AD is not fully understood. We hypothesized that abnormal sphingolipid metabolism in mitochondria could be one of the contributing factors to mitochondrial dysfunction. Synaptic and non-synaptic mitochondria were isolated from 5xFAD and wild type (WT) mice at 3 and 7 months using Ficoll gradient ultracentrifugation, and their function was analyzed using Seahorse assay. Additionally, mitochondria were ana- lyzed using mass spectrometry for proteomics and sphingolipidomics analyses. Sphingolipid levels were also determined in …

The Carboxy Terminus Causes Interfacial Assembly Of Oleate Hydratase On A Membrane Bilayer, Christopher D. Radka, Christy R. Grace, Hale S. Hasdemir, Yupeng Li, Carlos C. Rodriguez, Patrick Rodrigues, Michael L. Oldham, M. Zuhaib Qayyum, Aaron Pitre, William J. Maccain, Ravi C. Kalathur, Emad Tajkhorshid, Charles O. Rock

Markey Cancer Center Faculty Publications

The soluble flavoprotein oleate hydratase (OhyA) hydrates the 9-cis double bond of unsaturated fatty acids. OhyA sub- strates are embedded in membrane bilayers; OhyA must remove the fatty acid from the bilayer and enclose it in the active site. Here, we show that the positively charged helix- turn-helix motif in the carboxy terminus (CTD) is responsible for interacting with the negatively charged phosphatidylgly- cerol (PG) bilayer. Super-resolution microscopy of Staphylo- coccus aureus cells expressing green fluorescent protein fused to OhyA or the CTD sequence shows subcellular localization along the cellular boundary, indicating OhyA is membrane- associated and the CTD sequence …

Extended Conformations Of Bifurcating Electron Transfer Flavoprotein Constitute Up To Half The Population, Possibly Mediating Conformational Change, Sharique A. Khan, Alan Hicks, Wellington C. Leite, James Byrnes, Biswajit Gorai, Maria-Andrea Mroginski, Hugh O'Neill, Anne-Francis Miller

Markey Cancer Center Faculty Publications

Electron transfer bifurcation enables biological systems to drive unfavourable (endergonic) electron transfer by coupling it to favourable (exergonic) transfer of a second electron. In electron transfer flavoproteins (ETFs), a domain-scale conformational change is believed to sever the favourable pathway after a single electron has used it, thereby preventing the energy dissipation that would accompany exergonic transfer of the second electron. To understand the conformation change that participates in turnover, we have deployed small-angle neutron scattering (SANS) and computational techniques to characterize the bifurcating ETF from Acidaminococcus fermentans (AfeETF). SANS data reveal an overall radius of gyration (Rg) of 30.1 ± …

Strategies For Improving The Performance Of Prediction Models For Response To Immune Checkpoint Blockade Therapy In Cancer, Tiantian Zeng, Jason Z. Zhang, Arnold Stromberg, Jin Chen, Chi Wang

Markey Cancer Center Faculty Publications

Immune checkpoint blockade (ICB) therapy holds promise for bringing long-lasting clinical gains for the treatment of cancer. However, studies show that only a fraction of patients respond to the treatment. In this regard, it is valu- able to develop gene expression signatures based on RNA sequencing (RNAseq) data and machine learning meth- ods to predict a patient’s response to the ICB therapy, which contributes to more personalized treatment strategy and better management of cancer patients. However, due to the limited sample size of ICB trials with RNAseq data available and the vast number of candidate gene expression features, it is …

Tyrp1 Is The Mendelian Determinant Of The Axolotl (Ambystoma Mexicanum) Copper Mutant, Raissa F. Cecil, Lloyd Strohl, Maddie K. Thomas, James L. Schwartz, Nataliya Timoshevskaya, Jeramiah J. Smith, S. Randal Voss

Markey Cancer Center Faculty Publications

Several dozen Mendelian mutants have been discovered in axolotl (Ambystoma mexicanum) populations, including several that affect pigmentation. Four recessive mutants have been described in the scientific literature and genes for three of these have been identified. Here we describe and genetically dissect copper, a mutant with an albino-like phenotype known only from the pet trade. We performed a cross segregating copper and wildtype color phenotypes and used bulked segregant RNA-Seq to identify a region on chromosome 6 that was enriched for single-nucleotide polymorphisms (SNPs) between the color phenotypes. This region included Tyrosinase-like Protein 1 (Tyrp1), a melanin synthesis protein that …

Vaginal Lactobacillus Fatty Acid Response Mechanisms Reveal A Metabolite-Targeted Strategy For Bacterial Vaginosis Treatment, Paul C. Blainey, Seth M. Bloom, Douglas S. Kwon

Markey Cancer Center Faculty Publications

Bacterial vaginosis (BV), a common syndrome characterized by Lactobacillus-deficient vaginal microbiota, is associated with adverse health outcomes. BV often recurs after standard antibiotic therapy in part because antibiotics promote microbiota dominance by Lactobacillus iners instead of Lactobacillus crispatus, which has more beneficial health associations. Strategies to promote L. crispatus and inhibit L. iners are thus needed. We show that oleic acid (OA) and similar long-chain fatty acids simultaneously inhibit L. iners and enhance L. crispatus growth. These phenotypes require OA-inducible genes conserved in L. crispatus and related lactobacilli, including an oleate hydratase (ohyA) and putative fatty acid efflux pump (farE). …

Elevated Free Cholesterol Levels Due To Impaired Reverse Cholesterol Transport Are A Risk Factor For Polymicrobial Sepsis In Mice, Qian Wang, Ling Guo, Dan Hao, Misa Ito, Chieko Mineo, Philip W. Shaul, Xiang-An Li

Markey Cancer Center Faculty Publications

Dysregulated lipid metabolism is commonly observed in septic patients, but how it contributes to sepsis remains largely unknown. Reverse cholesterol transport (RCT) is crucial for regulating cholesterol metabolism in circulation. During RCT, high-density lipoprotein collects cholesterol from peripheral tissues and transports it to the liver’s scavenger receptor BI (SR- BI), where SR-BI mediates the uptake of cholesteryl esters (CEs) from high-density lipoprotein for excretion via bile. In this study, we utilized AlbCreSR-BIfl/fl mice, a model with impaired RCT, to investigate the impact of RCT on sepsis. We found that AlbCreSR-BIfl/fl mice were significantly more susceptible to cecal ligation and puncture …

Nudcl2 Is Required For Cytokinesis By Stabilizing Rcc2 With Hsp90 At The Midbody, Xiaoyang Xu, Yuliang Huang, Feng Yang, Xiaoxia Sun, Rijin Lin, Jiaxing Feng, Mingyang Yang, Jiaqi Shao, Xiaoqi Liu, Tianhua Zhou, Shanshan Xie, Yuehong Yang

Markey Cancer Center Faculty Publications

Cytokinesis is required for faithful division of cytoplasmic components and duplicated nuclei into two daughter cells. Midbody, a protein-dense organelle that forms at the intercellular bridge, is indispensable for success- ful cytokinesis. However, the regulatory mechanism of cytokinesis at the midbody still remains elusive. Here, we unveil a critical role for NudC-like protein 2 (NudCL2), a co-chaperone of heat shock protein 90 (Hsp90), in cytokinesis regulation by stabilizing regulator of chromosome condensation 2 (RCC2) at the midbody in mam- malian cells. NudCL2 localizes at the midbody, and its downregulation results in cytokinesis failure, multinu- cleation, and midbody disorganization. Using iTRAQ-based …

Rnf20 Contributes To Epigenetic Immunosuppression Through Cdk9- Dependent Lsd1 Stabilization, Bo Dong, Xinzhao Wang, Xiang Song, Jianlin Wang, Xia Liu, Zhiyong Yu, Yongkun Zhou, Jiong Deng, Yadi Wu

Markey Cancer Center Faculty Publications

Cyclin- dependent kinase 9 (CDK9) plays a critical role in transcription initiation and is essential for maintaining gene silencing at heterochromatic loci. Inhibition of CDK9 increases sensitivity to immunotherapy, but the underlying mechanism remains unclear. We now report that RNF20 stabilizes LSD1 via K29-mediated ubiquitination, which is dependent on CDK9- mediated phosphorylation. This CDK9- and RNF20- dependent LSD1 stabilization is necessary for the demethylation of histone H3K4, then subsequent repression of endogenous retrovirus, and an interferon response, leading to epigenetic immunosuppression. Moreover, we found that loss of RNF20 sensitizes cancer cells to the immune checkpoint inhibitor anti-PD- 1 in vivo …

Enhancing Translation: A Need To Leverage Complex Preclinical Models Of Addictive Drugs To Accelerate Substance Use Treatment Options, Christa Corley, Ashley Craig, Safiyah M. Sadek, Julie A. Marusich, Samar N. Chehimi, Ashley M. White, Lexi J. Holdiness, Benjamin C. Reiner, Cassandra D. Gipson

Markey Cancer Center Faculty Publications

Preclinical models of addictive drugs have been developed for decades to model aspects of the clinical experience in substance use disorders (SUDs). These include passive exposure as well as volitional intake models across addictive drugs and have been utilized to also measure withdrawal symptomatology and potential neuro- behavioral mechanisms underlying relapse to drug seeking or taking. There are a number of Food and Drug Administration (FDA)-approved medications for SUDs, however, many demonstrate low clinical efficacy as well as potential sex differences, and we also note gaps in the continuum of care for certain aspects of clinical ex- periences in individuals …

Biliverdin Reductase-A Integrates Insulin Signaling With Mitochondrial Metabolism Through Phosphorylation Of Gsk3Β, Chiara Lanzillotta, Antonella Tramutola, Simona Lanzillotta, Viviana Greco, Sara Pagnotta, Caterina Sanchini, Silvia Di Angelantonio, Elena Forte, Serena Rinaldo, Alessio Paone, Francesca Cutruzzolà, Flavia Agata Cimini, Ilaria Barchetta, Maria Gisella Cavallo, Andrea Urbani, D. Allan Butterfield, Fabio Di Domenico, Bindu D. Paul, Marzia Perluigi, Joao M.N. Duarte

Markey Cancer Center Faculty Publications

Brain insulin resistance links the failure of energy metabolism with cognitive decline in both type 2 Diabetes Mellitus (T2D) and Alzheimer’s disease (AD), although the molecular changes preceding overt brain insulin resistance remain unexplored. Abnormal biliverdin reductase-A (BVR-A) levels were observed in both T2D and AD and were associated with insulin resistance. Here, we demonstrate that reduced BVR-A levels alter insulin signaling and mitochondrial bioenergetics in the brain. Loss of BVR-A leads to IRS1 hyper-activation but dys- regulates Akt-GSK3β complex in response to insulin, hindering the accumulation of pGSK3βS9 into the mito- chondria. This event impairs oxidative phosphorylation and fosters …

Therapeutic Potential Of Berberine In Attenuating Cholestatic Liver Injury: Insights From A Psc Mouse Model, Yanyan Wang, Derrick Zhao, Lianyong Su, Yun-Ling Tai, Grayson W. Way, Jing Zeng, Qianhua Yan, Ying Xu, Xuan Wang, Emily C. Gurley, Xi-Qiao Zhou, Jinze Liu, Jinpeng Liu, Weidong Chen, Philip B. Hylemon, Huiping Zhou

Markey Cancer Center Faculty Publications

Background and aims

Primary sclerosing cholangitis (PSC) is a chronic liver disease characterized by progressive biliary inflammation and bile duct injury. Berberine (BBR) is a bioactive isoquinoline alkaloid found in various herbs and has multiple beneficial effects on metabolic and inflammatory diseases, including liver diseases. This study aimed to examine the therapeutic effect of BBR on cholestatic liver injury in a PSC mouse model (Mdr2 −/− mice) and eluci‑ date the underlying mechanisms.

Methods

Mdr2−/− mice (12–14 weeks old, both sexes) received either BBR (50 mg/kg) or control solution daily for eight weeks via oral gavage. Histological and serum biochemical …

Mechanisms Of Γδ T Cell Accumulation In Visceral Adipose Tissue With Aging, Sujata Mukherjee, Maria E. C. Bruno, Jason Oakes, Gregory S. Hawk, Arnold Stromberg, Donald A. Cohen, Marlene E. Starr

Markey Cancer Center Faculty Publications

γδ T cells are resident in visceral adipose tissue (VAT) where they show an age- associated increase in numbers and contribute to local and systemic chronic inflammation. However, regulation of this population and mechanisms for the age-dependent accumulation are not known. In this study, we identified a progressive trend of γδ T cell accumulation in VAT over the lifespan in mice and explored physiological mechanisms contributing to accumulation. Using isochronic parabiotic pairs of wild-type (WT) and T cell receptor delta knockout (TCRδ KO) mice at young and old age, we confirmed that VAT γδ T cells are predominately a tissue-resident …

Pai-1 As A Critical Factor In The Resolution Of Sepsis And Acute Kidney Injury In Old Age, Maria E. C. Bruno, Sujata Mukherjee, Jamie L. Sturgill, Virgilius Cornea, Peng Yeh, Gregory S. Hawk, Hiroshi Saito, Marlene E. Starr

Markey Cancer Center Faculty Publications

Elevated plasma levels of plasminogen activator inhibitor type 1 (PAI-1) are documented in patients with sepsis and levels positively correlate with disease severity and mortality. Our prior work demonstrated that PAI-1 in plasma is positively associated with acute kidney injury (AKI) in septic patients and mice. The objective of this study was to determine if PAI-1 is causally related to AKI and worse sepsis outcomes using a clinically-relevant and age-appropriate murine model of sepsis. Sepsis was induced by cecal slurry (CS)-injection to wild-type (WT, C57BL/6) and PAI-1 knockout (KO) mice at young (5–9 months) and old (18–22 months) age. Survival …

An Intelligent Search & Retrieval System (Iris) And Clinical And Research Repository For Decision Support Based On Machine Learning And Joint Kernel-Based Supervised Hashing., David J Foran, Wenjin Chen, Tahsin Kurc, Rajarshi Gupta, Jakub Roman Kaczmarzyk, Luke Austin Torre-Healy, Erich Bremer, Samuel Ajjarapu, Nhan Do, Gerald Harris, Antoinette Stroup, Eric B. Durbin, Joel H Saltz

Markey Cancer Center Faculty Publications

Large-scale, multi-site collaboration is becoming indispensable for a wide range of research and clinical activities in oncology. To facilitate the next generation of advances in cancer biology, precision oncology and the population sciences it will be necessary to develop and implement data management and analytic tools that empower investigators to reliably and objectively detect, characterize and chronicle the phenotypic and genomic changes that occur during the transformation from the benign to cancerous state and throughout the course of disease progression. To facilitate these efforts it is incumbent upon the informatics community to establish the workflows and architectures that automate the …

Impact Of Age >70 Years On Oncological Outcomes In Patients With Non-Muscle-Invasive Bladder Cancer Treated With Bacillus Calmette-Guérin., Roberto Contieri, Valentina Grajales, Wei Shen Tan, Alberto Martini, Akshay Sood, Patrick J. Hensley, Kelly Bree, Niyati Lobo, Graciela M. Nogueras-Gonzalez, Charles C. Guo, Neema Navai, Colin P. Dinney, Ashish M. Kamat

Markey Cancer Center Faculty Publications

OBJECTIVE: To evaluate the impact of age on oncological outcomes in a large contemporary cohort of patients with non-muscle-invasive bladder cancer (NMIBC) treated with adequate Bacillus Calmette-Guérin (BCG).

PATIENTS AND METHODS: We performed an Institutional Review Board-approved retrospective study analysing patients with NMIBC treated with adequate BCG at our institution from 2000 to 2020. Adequate BCG was defined as per United States Food and Drug Administration (FDA) guidelines as being receipt of at least five of six induction BCG instillations with a minimum of two additional doses (of planned maintenance or of re-induction) of BCG instillations within a span of …

Population-Level Incidence Of Human Papillomavirus–Positive Oropharyngeal, Cervical, And Anal Cancers, By Smoking Status, Sameer V. Gopalani, Mona Saraiya, Bin Huang, Thomas Tucker, Jacqueline M. Mix, Anil K. Chaturvedi

Markey Cancer Center Faculty Publications

We estimated the population-level incidence of human papillomavirus (HPV)–positive oropharyngeal, cervical, and anal cancers by smoking status. We combined HPV DNA genotyping data from the Centers for Disease Control and Prevention’s Cancer Registry Sentinel Surveillance System with data from the Kentucky Cancer Registry and Behavioral Risk Factor Surveillance System across smoking status. During 2004-2005 and 2014-2015 in Kentucky, most cases of oropharyngeal (63.3%), anal (59.7%), and cervical (54.9%) cancer were among individuals who ever smoked. The population-level incidence rate was higher among individuals who ever smoked than among those who never smoked for HPV-positive oropharyngeal (7.8 vs 2.1; adjusted incidence …

A Novel Protozoa Parasite-Derived Protein Adjuvant Is Effective In Immunization With Cancer Cells To Activate The Cancer-Specific Protective Immunity And Inhibit The Cancer Growth In A Murine Model Of Colorectal Cancer, Rajesh Mani, Chloe G. Martin, Kanal E. Balu, Qingding Wang, Piotr G. Rychahou, Tadahide Izumi, B. Mark Evers, Yasuhiro Suzuki

Markey Cancer Center Faculty Publications

Cancer-specific CD8+ cytotoxic T cells play important roles in preventing cancer growth, and IFN-γ, in addition to IL-12 and type I interferon, is critical for activating CD8+ cytotoxic T cells. We recently identified the capability of the amino-terminus region of dense granule protein 6 (GRA6Nt) of Toxoplasma gondii, an intracellular protozoan parasite, to activate IFN-γ production of microglia, a tissue-resident macrophage population. Therefore, in the present study, we examined whether recombinant GRA6Nt protein (rGRA6Nt) functions as an effective adjuvant to potently activate cancer-specific protective immunity using a murine model of MC38 colorectal cancer (CRC). When mice were immunized with non-replicable …

Structure, Dynamics, And Redox Reactivity Of An All-Purpose Flavodoxin, Sharique Khan, Ahmadullah Ansari, Monica Brachi, Debarati Das, Wassim El Housseini, Shelley Minteer, Anne-Francis Miller

Markey Cancer Center Faculty Publications

The flavodoxin of Rhodopseudomonas palustris CGA009 (Rp9Fld) supplies highly reducing equivalents to crucial en- zymes such as hydrogenase, especially when the organism is iron-restricted. By acquiring those electrons from photodriven electron flow via the bifurcating electron transfer flavoprotein, Rp9Fld provides solar power to vital metabolic processes. To understand Rp9Fld’s ability to work with diverse partners, we solved its crystal structure. We observed the canonical fla- vodoxin (Fld) fold and features common to other long-chain Flds but not all the surface loops thought to recognize part- ner proteins. Moreover, some of the loops display alternative structures and dynamics. To advance studies …