Medical Specialties Commons^™

Impact Of Sensory Diets On Occupational Performance, Kyndra Holloway, Cassandra Howard, Makena Collin, Princess Pillos

Occupational Therapy | MSOT Capstone Projects

This study investigates the impact of individualized sensory diets on children’s occupational performance in daily life. Sensory diets are structured, child-specific interventions designed to facilitate improved sensory processing by integrating activities into established routines. They involve a tailored home program plan, consistent application, and interventions aligned with the child’s specific sensory needs (Wilbarger, 1995).Using a multiple single-case study design, this research examined the outcomes of sensory diets prescribed alongside direct occupational therapy (OT) services for four white male children aged 3 years, 11 months to 5 years, and 8 months with neurodevelopmental disorders.

Participants were recruited through Developmental FX (DFX) …

Synthesis And Characterization Of Multifunctional Cerium Oxide Containing Nanoparticles For Biomedical Applications, Ishaan Patel

Honors Undergraduate Theses

This study presents the synthesis and comprehensive characterization of a novel core-shell nanoparticle composed of a maghemite (γ-Fe₂O₃) core and a europium-doped cerium oxide (EuCNP) shell, developed for potential use in cancer theranostics. Using a co-precipitation method, Fe₂O₃–EuCNP core-shell nanoparticles were synthesized and compared against control samples of CNPs, EuCNPs, and Fe₂O₃. A variety of characterization techniques, including UV-Vis spectroscopy, fluorescence spectroscopy, TEM, XRD, XPS, DLS, TGA, and DSC confirmed the successful synthesis of core-shell architecture and europium doping. Moreover, Fe₂O₃–EuCNPs demonstrating strong colloidal …

Investigating The Role Of Prostasin In Angiogenesis: A Chorioallantoic Membrane Model Approach, Zaima Aline

Honors Undergraduate Theses

Prostasin, also known as PRSS8 or CAP1, is a glycosylphosphatidylinositol (GPI)-anchored extracellular serine protease involved in various physiological and pathophysiological processes. Prostasin expression is observed during key phases of trophoblast invasion and placental development, critical steps in embryo implantation in Rhesus monkeys. This suggests a role for prostasin in extracellular matrix remodeling and tissue invasion, both essential for a healthy pregnancy. Moreover, prostasin appears vital for development as studies in mice show that a germline knockout of the gene leads to significant placental defects and eventual embryonic death, highlighting its importance in vascular and structural development within the placenta.

Building …

Effect Of Implementing An Educational Program About Post Kidney Transplant Care On Critical Care Nurses' Knowledge, Marwa Abdo, Asmaa Ibrahim Aboseda

Nursing

Background: Critical care nurses (CCNs) play a pivotal role in post-kidney transplant care, necessitating a comprehensive understanding of transplantation procedures, complications, and patient management. So, any knowledge gaps among CCNs may impact the quality of care provide to kidney transplant program. Aim: This study aimed to assess the effect of implementing an educational program about post-kidney transplant care on critical care nurses’ knowledge. Methods: A quasi-experimental study was conducted among 50 critical care nurses. A structured educational program was implemented, and nurses’ knowledge was assessed pre- program, post- program, and three months follow-up. Data was collected using a kidney transplantation …

Facilitation Of Chemotherapy Efficacy Through Targeted Drug Delivery In Lung Cancer Cells Via Ultrasound And Implications On Health Interventions, Ibrahim Nasim

Honors Undergraduate Theses

Lung Cancer (small cell and non-small cell) is the leading cause of cancer death in the US, accounting for about 20% of all cancer deaths. Paclitaxel (PTX) is a chemotherapeutic agent commonly used to treat lung cancer. It works by slowing and stopping cancer growth by stiffening microtubules within cells, promoting mitotic halt and cell death. Carboplatin (CP) is another agent given to lung cancer patients containing platinum and works via direct damage of oncolytic DNA. The exact mechanism of how PTX and CP cause cell death is still an under-studied area. This thesis aims to provide insight into how …

Meta-Analysis Of The Effect Of Vagus Nerve Stimulation On Functional Heart Failure Outcomes, Ariana B. Labrada

Honors Undergraduate Theses

Globally, Heart Failure (HF) is a significant cause for concern. Vagus Nerve Stimulation (VNS) is an emerging therapy for patients with HF. It involves the activation of efferent vagal signals, which result in the release of acetylcholine (ACh). In practice, VNS has obtained relatively mixed results in clinical trials so far. In order to ascertain the extent of the effects VNS has on functional clinical outcomes, this meta-analysis consolidates studies that involve patients with Heart Failure with reduced Ejection Fraction (HFrEF) and Heart Failure with preserved Ejection Fraction (HFpEF). Outcomes were measured through the change in mean heart rate (HR) …

High-Throughput Drug Screening For Disease-Modifying Arthritis Therapy, Janapriya Vijayakumar

Honors Undergraduate Theses

Current therapy for arthritis predominantly focuses on the symptoms rather than the underlying causes of disease progression. Thus, it is necessary to identify novel drugs which target the underlying molecular basis of such diseases. Using high-throughput cell-based drug screening, we screened 458 different compounds, narrowed down from 811 starting compounds from the NIH Mechanistic Set. We selected drugs from the Mechanistic Set following Lipinski's Rule of 5 to ensure optimal pharmacokinetic properties. The study used modified primary human chondrocytes (IIAM-PRG4Luc), which secrete a lubricin promoter-driven luciferase reporter. We use this luciferase expression as a proxy to measure lubricin, a compound …

Investigation Of Lubricin-Stimulating Fda-Approved Compounds For A Disease-Modifying Osteoarthritic Drug, Swathi S. Menon

Honors Undergraduate Theses

Osteoarthritis (OA) is a degenerative disease that affects many people worldwide. Current methods of treatment are palliative, and no treatment exists to fully reverse or cure OA once it begins to progress. The discovery of a disease-modifying osteoarthritic drug (DMOAD) would increase the quality of life for millions and reduce the need for invasive procedures. Screening FDA-approved drugs ensures more promise due to their known safety profile and potential for faster translation to the clinic. The goal of this project was to conduct dose-response assays with FDA-approved drugs that have been shown to stimulate lubricin production in cells that mimic …

Development Of A Proposed Selective Medium For The Isolation And Differentiation Of P. Sordellii, Dimyana Bottros

Honors Undergraduate Theses

Clostridium, a genus of anaerobic, spore-forming bacteria, includes clinically and ecologically significant species like Clostridium difficile and Paeniclostridium sordellii. C. difficile causes antibiotic-associated colitis, while P. sordellii is linked to fatal infections and spontaneous abortions. Recent studies found both species in marine sediments, suggesting their role in environmental and wildlife health disturbances, including the 2013 mass mortality of over 300 manatees in the Indian River Lagoon. However, isolating and differentiating P. sordellii is challenging due to the lack of selective media optimized for its growth. This thesis proposes a novel selective medium tailored to P. sordellii’s physiological …

Investigating Mono-Driver Versus Multi-Driver Oncogenesis Via Alterations To Cell Signaling Pathways, Abygail Chapdelaine

Open Access Dissertations

The latest edition of Global Cancer Statistics released by the American Cancer Society reported approximately 20 million newly diagnosed cancer cases worldwide in 2022 with 9.7 million deaths. This ranks cancer as the second leading cause of death worldwide. For the majority of cancer patients, the standard treatment approach is chemotherapy and/or radiation therapy, and while this has been successful in some patients, a lack of specificity to cancer cells causes severe side-effects when these agents damage healthy cells. Despite extensive efforts that have gone into developing targeted cancer therapeutics that block functions specific to cancer, they have not been …

Tam Receptors Mediate The Fpr2-Driven Pain Resolution And Fibrinolysis After Nerve Injury, Beate Hartmannsberger, Adel Ben‑Kraiem, Sofia Kramer, Carolina Guidolin, Ida Kazerani, Kathrin Doppler, Dominique Thomas, Robert Gurke, Marco Sisignano, Pranav P. Kalelkar, Andrés J. García, Paula V. Monje, Michael Sammeth, Asma Nusrat, Alexander Brack, Susanne M. Krug, Claudia Sommer, Heike L. Rittner

Markey Cancer Center Faculty Publications

Nerve injury causes neuropathic pain and multilevel nerve barrier disruption. Nerve barriers consist of perineurial, endothe- lial and myelin barriers. So far, it is unclear whether resealing nerve barriers fosters pain resolution and recovery. To this end, we analysed the nerve barrier property portfolio, pain behaviour battery and lipidomics for precursors of specialized pro-resolving meditators (SPMs) and their receptors in chronic constriction injury of the rat sciatic nerve to identify tar- gets for pain resolution by resealing the selected nerve barriers. Of the three nerve barriers—perineurium, capillaries and myelin—only capillary tightness specifically against larger molecules, such as fibrinogen, recuperated with …

Extracellular Vesicles Released By All Patients Contain Hne-Adducted Proteins: Implications Of Collateral Damage, Jenni Ho, Suriyan Sukati, Tamara Taylor, Sherry Carter, Brittany Fuller, Amy Marmo, Caryn Sorge, John A. D'Orazio, D. Allan Butterfield, Subbarao Bondada, Heidi Weiss, Daret K. St. Clair, Luksana Chaiswing

Markey Cancer Center Faculty Publications

Off-target neuronal injury is a serious side-effect observed in cancer survivors. It has previously been shown that pediatric acute lymphoblastic leukemia (ALL) survivors have a decline in neurocognition compared to healthy age-matched counterparts. Elevated oxidative stress has been documented to be a mediator in off- target tissue damage in cancer survivors. Early detection of oxidative stress markers may provide an opportunity to prevent off-target tissue damage. Extracellular vesicles (EVs) have surfaced as a potential diagnostic tool due to molecular cargo they contain. We investigated the potential for EVs to be a sensitive indicator of oxidative stress and off-target tissue damage …

Engaging Nurses In Effective Cost Of Care Conversations To Address Cancer-Related Financial Toxicity: Results From An Exploratory Survey, Jean Edward, Amanda T. Wiggins, Louis G. Baser, Haafsah Fariduddin, Joanna F. Doran, Monica F. Bryant, John August D'Orazio, Kimberly D. Northrip

Markey Cancer Center Faculty Publications

Few evidence-based trainings exist on how to equip healthcare providers, particularly nurses, with the skills to engage in cost of care conversations with patients/caregivers to mitigate the impact of cancer-related financial toxicity. This study evaluated a pilot training developed in collaboration with Triage Cancer® to prepare oncology nurses to identify and assist patients/caregivers facing financial and/or legal barriers to care. Ten pediatric oncology nurses completed the training and pre/post-surveys on behaviors related to financial and legal need screening, frequency and comfort level of answering questions, knowledge, and behavior changes, along with training evaluation questions. At baseline, six nurses reported never …

Pharmacological Or Genetic Inhibition Of Ltcc Promotes Cardiomyocyte Proliferation Through Inhibition Of Calcineurin Activity, Lynn A. C. Devilée, Abou Bakr M. Salama, Jessica M. Miller, Janice D. Reid, Qinghui Ou, Nourhan M. Baraka, Kamal Abou Farraj, Madiha Jamal, Yibing Nong, Todd K. Rosengart, Douglas A. Andres, Jonathan Satin, Tamer M. A. Mohamed, James E. Hudson, Riham R. E. Abouleisa

Markey Cancer Center Faculty Publications

Cardiomyocytes (CMs) lost during ischemic cardiac injury cannot be replaced due to their limited proliferative capacity. Calcium is an important signal transducer that regulates key cellular processes, but its role in regulating CM proliferation is incompletely understood. Here we show a robust pathway for new calcium signaling-based cardiac regenerative strategies. A drug screen targeting proteins involved in CM calcium cycling in human embryonic stem cell-derived cardiac organoids (hCOs) revealed that only the inhibition of L-Type Calcium Channel (LTCC) induced the CM cell cycle. Furthermore, overexpression of Ras-related associated with Diabetes (RRAD), an endogenous inhibitor of LTCC, induced CM cell cycle …

The Adiponectin-Pparγ Axis In Hepatic Stellate Cells Regulates Liver Fibrosis, Shangang Zhao, Qingzhang Zhu, Wang-Hsin Lee, Jan-Bernd Funcke, Zhuzhen Zhang, May-Yun Wang, Qian Lin, Bianca Field, Xue-Nan Sun, Guannan Li, Mbolle Ekane, Toshiharu Onodera, Na Li, Yi Zhu, Christine M. Kusminski, Terry D. Hinds Jr., Philipp E. Scherer

Markey Cancer Center Faculty Publications

Hepatic stellate cells (HSCs) are key drivers of local fibrosis. Adiponectin, conventionally thought of as an adipokine, is also expressed in quiescent HSCs. However, the impact of its local expression on the progression of liver fibrosis remains unclear. We recently generated a transgenic mouse line (Lrat-rtTA) that expresses the doxycycline-responsive transcriptional activator rtTA under the control of the HSC-specific lecithin retinol acyltransferase (Lrat) promoter, which enables us to specifically and inducibly overexpress or eliminate genes in these cells. The inducible elimination of HSCs protects mice from methionine/choline-deficient (MCD) diet-induced liver fibrosis, confirming their causal involvement in fibrosis development. We generated …

Urobilin Derived From Bilirubin Bioconversion Binds Albumin And May Interfere With Bilirubin Interacting With Albumin: Implications For Disease Pathology, Kevin I. Williams, Priyanka Suryadevara, Chang-Guo Zhan, Terry D. Hinds Jr., Zachary A. Kipp

Markey Cancer Center Faculty Publications

Background/Objectives: Bilirubin is a hydrophobic molecule that binds the carrier protein albumin for transport through systemic circulation. Bilirubin is cleared from the body through the liver and excreted into the intestines, where the microbiota modifies the chemical structure, forming urobilin, which can be reabsorbed into circulation by the hepatic portal vein. Urobilin has no known function. It is also unknown whether urobilin binds albumin for transport in circulation. We hypothesized that because of the likeness of their chemical structures, urobilin would also bind albumin like bilirubin does. Methods: First, we used in silico docking to predict if urobilin would bind …

Heme Oxygenase, Biliverdin Reductase, And Bilirubin Pathways Regulate Oxidative Stress And Insulin Resistance: A Focus On Diabetes And Therapeutics, Wang-Hsin Lee, Zachary A. Kipp, Sally Pauss, Genesee J. Martinez, Evelyn A. Bates, Olufunto O. Badmus, David E. Stec, Terry D. Hinds Jr.

Markey Cancer Center Faculty Publications

Metabolic and insulin-resistant diseases, such as type 2 diabetes mellitus (T2DM), have become major health issues worldwide. The prevalence of insulin resistance in the general population ranges from 15.5% to 44.6%. Shockingly, the global T2DM population is anticipated to double by 2050 compared with 2021. Prior studies indicate that oxidative stress and inflammation are instrumental in causing insulin resistance and instigating metabolic diseases. Numerous methods and drugs have been designed to combat insulin resistance, including metformin, thiazolidinediones (TZDs), sodium-glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide 1 receptor agonists (GLP1RA), and dipeptidyl peptidase 4 inhibitors (DPP4i). Bilirubin is an antioxidant with …

Dissecting The Biophysical Mechanisms Of Oleate Hydratase Association With Membranes, William A. Lathram, Robert J. Neff, Ashley N. Zalla, James D. Brien, Vivekanandan Subramanian, Christopher D. Radka

Markey Cancer Center Faculty Publications

This study investigates the dynamics of oleate hydratase (OhyA), a bacterial flavoenzyme from Staphylococcus aureus, and its interactions with lipid membranes, focusing on the factors influencing membrane binding and oligomerization. OhyA catalyzes the hydration of unsaturated fatty acids, playing a key role in bacterial pathogenesis by neutralizing host antimicrobial fatty acids. OhyA binds the membrane bilayer to access membrane-embedded substrates for catalysis, and structural studies have revealed that OhyA forms oligomers on membrane surfaces, stabilized by both protein-protein and protein-lipid interactions. Using fluorescence correlation spectroscopy (FCS), we examined the effects of membrane curvature and lipid availability on OhyA binding to …

Advances In Magnetic Nanoparticles For Molecular Medicine, Xiaoyue Yang, Sarah E. Kubican, Zhongchao Yi, Sheng Tong

Markey Cancer Center Faculty Publications

Magnetic nanoparticles (MNPs) are highly versatile nanomaterials in nanomedicine, owing to their diverse magnetic properties, which can be tailored through variations in size, shape, composition, and exposure to inductive magnetic fields. Over four decades of research have led to the clinical approval or ongoing trials of several MNP formulations, fueling continued innovation. Beyond traditional applications in drug delivery, imaging, and cancer hyperthermia, MNPs have increasingly advanced into molecular medicine. Under external magnetic fields, MNPs can generate mechano- or thermal stimuli to modulate individual molecules or cells deep within tissue, offering precise, remote control of biological processes at cellular and molecular …

Mir-27a-3p Regulates Intestinal Cell Proliferation And Differentiation Through Wnt/Β-Catenin Signalling, Chang Li, Yuning Zhou, Yinping Jiang, Zhijie Yin, Heidi L. Weiss, Qingding Wang, B. Mark Evers

Markey Cancer Center Faculty Publications

Intestinal stem cells differentiate into absorptive enterocytes, characterised by increased brush border enzymes such as intestinal alkaline phosphatase (IAP), making up the majority (95%) of the terminally differentiated cells in the villus. Loss of integrity of the intestinal epithelium plays a key role in inflammatory diseases and gastrointestinal infection. Here, we show that the intestinal microRNA (miR)-27a-3p is an important regulator of intestinal epithelial cell proliferation and enterocyte differentiation. Repression of endogenous miR-27a-3p leads to increased enterocyte differentiation and decreased intestinal epithelial cell proliferation in mouse and human small intestinal organoids. Mechanistically, miR-27a-3p regulates intestinal cell differentiation and proliferation at …

Engaging Nurses In Effective Cost Of Care Conversations To Address Cancer-Related Financial Toxicity: Results From An Exploratory Survey, Jean Edward, Abigail Wiggins, Louis G. Baser, Haafsah Fariduddin, Joanna F. Doran, Monica F. Bryant, John A. D'Orazio, Kimberly D. Northrip

Markey Cancer Center Faculty Publications

Few evidence-based trainings exist on how to equip healthcare providers, particularly nurses, with the skills to engage in cost of care conversations with patients/caregivers to mitigate the impact of cancer-related financial toxicity. This study evaluated a pilot training developed in collaboration with Triage Cancer® to prepare oncology nurses to identify and assist patients/caregivers facing financial and/or legal barriers to care. Ten pediatric oncology nurses completed the training and pre/post-surveys on behaviors related to financial and legal need screening, frequency and comfort level of answering questions, knowledge, and behavior changes, along with training evaluation questions. At baseline, six nurses reported never …

Association Between Education And Allostatic Load With Risk Of Cancer Mortality Among Hispanic Women, Melissa Lopez-Pentecost, Cynthia Li, Marlo Vernon, Sydney P. Howard, Jessica Amezcua, Justin Xavier Moore

Markey Cancer Center Faculty Publications

Purpose: Cancer remains the leading cause of death among Hispanics in the US. While social determinants of health, such as educational attainment, have been linked to negative health outcomes, their biological mechanisms remain poorly understood. We evaluated the association between educational attainment and allostatic load (AL), a measure of chronic physiologic stress, with risk of cancer mortality in Hispanic women from the National Health and Nutrition Examination Survey (NHANES).

Methods: We performed a retrospective analysis among 5637 Hispanic women in NHANES from 1988 to 2010 with follow-up data through 2019. Educational attainment was categorized into a two-level variable: less than …

Functional Assessment Of Migration And Adhesion To Quantify Cancer Cell Aggression, Lauren E. Mehanna, James D. Boyd, Chloe G. Walker, Adrianna R. Osborne, Martha E. Grady, Brad J. Berron

Markey Cancer Center Faculty Publications

During epithelial-to-mesenchymal transition (EMT), cancer cells lose their cell–cell adhesion junctions as they become more metastatic, altering cell motility and focal adhesion disassembly associated with increased detachment from the primary tumor and a migratory response into nearby tissue and vasculature. Current in vitro strategies characterizing a cell’s metastatic potential heavily favor quantifying the presence of cell adhesion biomarkers through biochemical analysis; however, mechanical cues such as adhesion and motility directly relate to cell metastatic potential without needing to first identify a cell specific biomarker for a particular type of cancer. This paper presents a comprehensive comparison of two functional metrics …

Inclusion Of Surgery In Multimodality Treatment Is Predictive Of Better Survival In Stage Iiia Non-Small Cell Lung Cancer: An Inverse Probability Treatment-Weighting Analysis, Feitong Lei, Janeesh Sekkath-Veedu, Bin Huang, Quan Chen, Mansi Shah-Jadeja, Thomas E. Stinchcombe, Zhonglin Hao

Markey Cancer Center Faculty Publications

Introduction: Stage IIIA non-small cell lung cancers (NSCLC) are treated with surgery-based multimodality approach or definitive chemoradiation therapy plus durvalumab consolidation. It is not clear whether surgery-based multimodality therapy has any survival advantage over definitive chemoradiation plus immunotherapy consolidation.

Method: National Cancer Database (NCDB) was used to identify NSCLC patients at stage IIIA (AJCC8, T3N1/T4N0-1 or T1N2/T2N2) who are treated with surgery-based multimodality approach or definitive chemoradiation plus durvalumab. Survival between groups were compared using inverse probability treatment weighting (IPTW)-adjusted Kaplan Meier curves and Cox proportional hazards regression analysis. Results were independently confirmed by Landmark Inverse and Clone Censor Weight …

M1 Macrophage‑Engineered Vesicles Have Anti‑Cancer Activity In Ovarian Cancer, Connie D. Cao, J. Robert Mccorkle, Derek B. Allison, Donglin Yan, Kristen S. Hill, Lan Li, Rani Jayswal, David Schweer, Charles S. Dietrich Iii, Frederick R. Ueland, Christopher I. Richards, Jill M. Kolesar

Markey Cancer Center Faculty Publications

Background: Ovarian cancer typically presents at an advanced stage, has a poor prognosis, and is a leading cause of cancer-related deaths in women. Extracellular vesicles (EVs) are cell membrane-derived nanoparticles that function in specific cell- to-cell communication and are under development as novel drug delivery vehicles and modulators of the tumor microenvironment. Artificial cell-derived vesicles (ACDVs) from M1 macrophages are able to repolarize macrophages from a M2 to a M1 phenotype and target tumor cells in in vitro studies.

Results: In this study, we generated engineered EVs (EEVs) by membrane disruption of M1 macrophages (MEVs) with and without cisplatin to …

Measuring The Impact Of A Catchment Area Surveillance Tool On Cancer Center Adopters, Todd Burus, Caree R. Mcafee, Natalie P. Wilhite, Pamela C. Hull

Markey Cancer Center Faculty Publications

Background: The University of Kentucky Markey Cancer Center developed the data gathering and visualization platform Cancer InFocus (CIF) as a solution for cancer center catchment area surveillance. CIF was released in June 2022 and made available for use to other institutions through a no‐cost licensing agreement. The purpose of this study was to evaluate the impact CIF has had on cancer centers since its release.

Methods: The authors adapted an existing management evaluation framework to assess the impact of CIF across three spheres—idea dissemination, product engagement, and adopter satisfaction. This assessment included an online survey administered between the dates of …

Tracking Community Outreach And Engagement Activities Among National Cancer Institute-Designated Cancer Centers, Todd Burus, Caree R. Mcafee, Pamela C. Hull, Amy E. Leader, Christopher Mcnair

Markey Cancer Center Faculty Publications

The National Cancer Institute’s (NCI) Cancer Center Support Grant mandates that NCI-designated cancer centers establish a Community Outreach and Engagement (COE) component to help direct efforts at reducing cancer burden within their catchment areas. Despite the critical role of COE offices, little is known about how they track and evaluate outreach activities and outcomes. We gathered information on current practices from representatives of 40 out of 65 COE offices using an online survey. Although nearly all responding centers (97.5%) tracked COE activities, no consensus existed on resources used, and satisfaction with current solutions was mixed (51.0% not satisfied). Respondents expressed …

Biparental Inheritance Of Germline-Specific Chromosomes In The Sea Lamprey And Their Roles In Oocytes, Vladimir A. Timoshevskiy, Nataliya Timoshevskaya, Kaan İ. Eşkut, Kasturi Rajandran, Jeramiah J. Smith

Markey Cancer Center Faculty Publications

Many eukaryotic species undergo programmed elimination of specific chromosomes during embryogenesis, typically retaining these chromosomes only in their germ cells. In some species, programmatic elimination of GRCs, or sex chromosomes, also occurs in a sex-specific manner, with specific chromosomes being transmitted or eliminated by only one sex. As such, these chromosomes provide a unique perspective on the evolution of gene functions that are advantageous to the germline and genetic tradeoffs between somatic vs germline or oocyte vs sperm biology. While GRCs have been extensively characterized in male sea lampreys (Petromyzon marinus), the status of GRCs in females has not yet …

Cryptic To Conventional Cytogenetics: Philadelphia- Like All Presenting With Hypereosinophilia, Zena Chahine, Leonard Yenwong Fai, Sainan Wei, Ayman Qasrawi

Markey Cancer Center Faculty Publications

BCR::ABL1-like B-lymphoblastic leukaemia (B-ALL) neoplasms lack the BCR::ABL1 translocation but have a gene expression profile like BCR::ABL1 positive B-ALL. This includes alterations in cytokine receptors and signalling genes, such as CRLF2, ABL1, ABL2, JAK2, PDGFRB and EPOR. Cases with CRLF2 rearrangements account for approximately 50% of cases of Philadelphia-like acute lymphoblastic leukaemia (Ph-like ALL), and the frequency of specific genomic lesions varies with ethnicity such that IGH::CRLF2 translocations are more common in Hispanics and Native Americans. We report two cases of BCR::ABL1-like ALL, with significant eosinophilia. A Hispanic man in his early 20s and a Hispanic woman in her 50s …

Cabozantinib Selectively Induces Proteasomal Degradation Of P53 Somatic Mutant Y220c And Impedes Tumor Growth, Fang Lin Lv, Lu Zhang, Cheng Ji, Lei Peng, Mingxian Zhu, Shumin Yang, Shunli Dong, Mingxuan Zhou, Fanfan Guo, Zhenyun Li, Fang Wang, Youguo Chen, Jinhua Zhou, Xingcong Ren, Genhai Shen, Jin-Ming Yang, Bin Li, Yi Zhang

Markey Cancer Center Faculty Publications

Inactivation of p53 by mutations commonly occurs in human cancer. The mutated p53 proteins may escape proteolytic degradation and exhibit high expression in tumors and acquire gain-of-function activity that promotes tumor progression and chemo-resistance. Therefore, selectively targeting of the gain-of-function p53 mutants may serve as a promising therapeutic strategy for cancer prevention and treatment. In this study, we identified cabozantinib, a multikinase inhibitor currently used in the clinical treatment of several types of cancer, as a selective inducer of proteasomal degradation of the p53-Y220C mutant. We demonstrate that cabozantinib disrupts the interaction between p53Y220C and USP7, a deubiquitylating enzyme, resulting …