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Colorectal Cancer: Differential Gene Expression And In Vitro Response To 5-Fluorouracil, Novel Fluoropyrimidine F10, And Potential Synergy With Lupeol, Shrey D. Thaker, Jenny Paredes, Jone Garai, Laura A. Martello, William H. Gmeiner, Jovanny Zabaleta, Jennie Williams Nov 2025

Colorectal Cancer: Differential Gene Expression And In Vitro Response To 5-Fluorouracil, Novel Fluoropyrimidine F10, And Potential Synergy With Lupeol, Shrey D. Thaker, Jenny Paredes, Jone Garai, Laura A. Martello, William H. Gmeiner, Jovanny Zabaleta, Jennie Williams

School of Medicine Faculty Publications

Colorectal cancer (CRC) remains one of the most lethal malignancies in the United States, with African American (AA) patients experiencing disproportionately higher incidence and mortality compared to Caucasian Americans (CAs). These disparities have been linked to tumor-intrinsic genomic differences, including microsatellite instability (MSI) and p53 mutation status, which may influence chemotherapeutic response, particularly to the standard-of-care agent 5-fluorouracil (5-FU). However, mechanistic insights have been limited by the lack of racially diverse preclinical models. Here, we evaluated the efficacy of F10 (a novel fluoropyrimidine polymer) vs. 5-FU using AA- and CA-derived CRC cell lines with distinct MSI and p53 profiles. MTT …


Cabotegravir Maintains Protective Efficacy In The Setting Of Bacterial Stis: A Secondary Analysis Of Hptn 083, Meredith E. Clement, Brett Hanscom, Daniel Haines, Jose A. Bazan, Nuntisa Chotirosniramit, Ryan Kofron, Sharon Mannheimer, Kenneth H. Mayer, Mayara Secco Torres Silva, Lydia Soto-Torres, Alex R. Rinehart, James F. Rooney, A Jennings, K Gomez-Feliciano, Marybeth Mccauley, Beatriz Grinsztejn, Raphael J. Landovitz, Et Al. Nov 2024

Cabotegravir Maintains Protective Efficacy In The Setting Of Bacterial Stis: A Secondary Analysis Of Hptn 083, Meredith E. Clement, Brett Hanscom, Daniel Haines, Jose A. Bazan, Nuntisa Chotirosniramit, Ryan Kofron, Sharon Mannheimer, Kenneth H. Mayer, Mayara Secco Torres Silva, Lydia Soto-Torres, Alex R. Rinehart, James F. Rooney, A Jennings, K Gomez-Feliciano, Marybeth Mccauley, Beatriz Grinsztejn, Raphael J. Landovitz, Et Al.

School of Medicine Faculty Publications

BACKGROUND: Sexually transmitted infections (STIs) have been shown to facilitate HIV transmission and acquisition. HPTN 083, a global clinical trial, demonstrated superiority of long-acting cabotegravir (CAB-LA) versus daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for HIV prevention among transgender women and cisgender men who have sex with men. This analysis assessed whether CAB-LA maintained protective efficacy when bacterial STIs (syphilis, rectal/urethral gonorrhea and chlamydia) were present. METHODS: STI events per 100 person-years (PY) were calculated, including by subgroups (age, race/ethnicity, gender, education, treatment arm, drug use, alcohol use, region/country, condom usage, partner number, marital status, baseline STI). Association between baseline factors …


Hyperbaric Oxygen Therapy In The Atls/Acls Resuscitative Management Of Acutely Ill Or Severely Injured Patients With Severe Anemia: A Review, Keith W. Van Meter Oct 2024

Hyperbaric Oxygen Therapy In The Atls/Acls Resuscitative Management Of Acutely Ill Or Severely Injured Patients With Severe Anemia: A Review, Keith W. Van Meter

School of Medicine Faculty Publications

For short periods, even without the presence of red blood cells, hyperbaric oxygen can safely allow plasma to meet the oxygen delivery requirements of a human at rest. By this means, hyperbaric oxygen, in special instances, may be used as a bridge to lessen blood transfusion requirements. Hyperbaric oxygen, applied intermittently, can readily avert oxygen toxicity while meeting the body's oxygen requirements. In acute injury or illness, accumulated oxygen debt is shadowed by adenosine triphosphate debt. Hyperbaric oxygen efficiently provides superior diffusion distances of oxygen in tissue compared to those provided by breathing normobaric oxygen. Intermittent application of hyperbaric oxygen …


Allopurinol: Clinical Considerations In The Development And Treatment Of Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis, And Other Associated Drug Reactions, Kathryn M. Dillman, Alison M. Hawkins, Amanda R. Ragland, Grace C. Wester, Driskell R. Greene, Giustino Varrassi, Peyton Moore, Raju Behara, Shahab Ahmadzadeh, Harish Siddaiah, Sahar Shekoohi, Alan D. Kaye Jul 2024

Allopurinol: Clinical Considerations In The Development And Treatment Of Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis, And Other Associated Drug Reactions, Kathryn M. Dillman, Alison M. Hawkins, Amanda R. Ragland, Grace C. Wester, Driskell R. Greene, Giustino Varrassi, Peyton Moore, Raju Behara, Shahab Ahmadzadeh, Harish Siddaiah, Sahar Shekoohi, Alan D. Kaye

School of Medicine Faculty Publications

Allopurinol lowers urate production through the inhibition of xanthine oxidase. It is oxidatively hydroxylated to oxypurinol and is the most prescribed medication for gout treatment. Although it has a beneficial effect in the treatment of this common disease, like many medications, it is also known for having numerous adverse effects. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), diseases that exist on a spectrum, are two of the most dangerous adverse effects associated with allopurinol use. These immune-mediated disease processes involve almost every organ system. They are essential to recognize as early as possible, as they could potentially be deadly, …


Odevixibat: A Novel Bile Salt Inhibitor Treatment For Pruritus In Progressive Familial Intrahepatic Cholestasis, Farrah E. Flattmann, Farhan S. Mohiuddin, Anjuni Singh, Anamika Tandon, Stewart J. Lockett, Jon D. Hirsch, Chizoba N. Mosieri, Adam M. Kaye, Giustino Varrassi, Shahab Ahmadzadeh, Sahar Shekoohi, Alan D. Kaye Mar 2024

Odevixibat: A Novel Bile Salt Inhibitor Treatment For Pruritus In Progressive Familial Intrahepatic Cholestasis, Farrah E. Flattmann, Farhan S. Mohiuddin, Anjuni Singh, Anamika Tandon, Stewart J. Lockett, Jon D. Hirsch, Chizoba N. Mosieri, Adam M. Kaye, Giustino Varrassi, Shahab Ahmadzadeh, Sahar Shekoohi, Alan D. Kaye

School of Medicine Faculty Publications

Chronic pruritus is defined as an itch lasting greater than six weeks. It can manifest from a wide variety of etiologies, as many different substances can act as pruritogens, such as steroids, histamine, progesterone, endogenous opioids, and serotonin. In the setting of cholestatic liver disease, increased bile acids play a major role in chronic pruritus. The itching in cholestatic liver disease is worsened in intensity at night and localized frequently to the palms, soles, knees, and other pressure sites. It can be hard to manage, affecting the quality of sleep and causing irritability, poor attention, and, in some cases, depression. …


Etiology Of Drug-Induced Edema: A Review Of Dihydropyridine, Thiazolidinedione, And Other Medications Causing Edema, Evan S. Sinnathamby, Bretton T. Urban, Robert A. Clark, Logan T. Roberts, Audrey J. De Witt, Danielle M. Wenger, Aya Mouhaffel, Olga Willett, Shahab Ahmadzadeh, Sahar Shekoohi, Alan D. Kaye, Giustino Varrassi Feb 2024

Etiology Of Drug-Induced Edema: A Review Of Dihydropyridine, Thiazolidinedione, And Other Medications Causing Edema, Evan S. Sinnathamby, Bretton T. Urban, Robert A. Clark, Logan T. Roberts, Audrey J. De Witt, Danielle M. Wenger, Aya Mouhaffel, Olga Willett, Shahab Ahmadzadeh, Sahar Shekoohi, Alan D. Kaye, Giustino Varrassi

School of Medicine Faculty Publications

Edema is an accumulation of fluid in the body's tissues that affects millions of Americans yearly. It can affect multiple body parts, for example, the brain or eyes, but often occurs in the periphery, including the feet and legs. Medications, such as dihydropyridine and thiazolidinediones (TZDs), can be the etiology of edema. Edema can develop in association with problems in the vasculature or lymphatic flow. In recent years, a better understanding of these drug-induced mechanisms has been appreciated. Specifically, dihydropyridines can increase hydrostatic pressure and cause selective pre-capillary vessel vasodilation. TZDs can cause edema through increased vascular permeability and increased …


Folate Deficiency Modifies The Risk Of Cin3+ Associated With Dna Methylation Levels: A Nested Case–Control Study From The Ascus-Col Trial, María C. Agudelo, Samuel Agudelo, Attila Lorincz, Arianis Tatiana Ramírez, Kelly Melisa Castañeda, Isabel Garcés-Palacio, Arnold H. Zea, Chandrika Piyathilake, Gloria Ines Sanchez Dec 2023

Folate Deficiency Modifies The Risk Of Cin3+ Associated With Dna Methylation Levels: A Nested Case–Control Study From The Ascus-Col Trial, María C. Agudelo, Samuel Agudelo, Attila Lorincz, Arianis Tatiana Ramírez, Kelly Melisa Castañeda, Isabel Garcés-Palacio, Arnold H. Zea, Chandrika Piyathilake, Gloria Ines Sanchez

School of Medicine Faculty Publications

Purpose: To our knowledge, there are very few studies evaluating if the levels of folate modify the risk of cervical intraepithelial neoplasia grade 2 and higher (CIN2+ and CIN3+) associated with the levels of HPV genome methylation, two cofactors related to single carbon metabolism and independently associated with cervical cancer in previous studies. We conducted a case–control study nested in a three-arm randomized clinical pragmatic trial (ASCUS-COL trial) to evaluate the risk of CIN3+ associated with methylation levels according to serum folate concentrations. Methods: Cases (n = 155) were women with histologically confirmed CIN2+ (113 CIN2, 38 CIN3, and 4 …


Minoxidil Weakens Newly Synthesized Collagen In Fibrotic Synoviocytes From Osteoarthritis Patients, Stefan Sarkovich, Peter P. Issa, Andrew Longanecker, Davis Martin, Kaitlyn Redondo, Patrick Mcternan, Jennifer Simkin, Luis Marrero Aug 2023

Minoxidil Weakens Newly Synthesized Collagen In Fibrotic Synoviocytes From Osteoarthritis Patients, Stefan Sarkovich, Peter P. Issa, Andrew Longanecker, Davis Martin, Kaitlyn Redondo, Patrick Mcternan, Jennifer Simkin, Luis Marrero

School of Medicine Faculty Publications

Purpose: Synovial fibrosis (SFb) formation and turnover attributable to knee osteoarthritis (KOA) can impart painful stiffness and persist following arthroplasty. To supplement joint conditioning aimed at maximizing peri-operative function, we evaluated the antifibrotic effect of Minoxidil (MXD) on formation of pyridinoline (Pyd) cross-links catalyzed by Plod2-encoded lysyl hydroxylase (LH)2b that strengthen newly synthesized type-I collagen (COL1) in fibroblastic synovial cells (FSCs) from KOA patients. MXD was predicted to decrease Pyd without significant alterations to Col1a1 transcription by FSCs stimulated with transforming growth factor (TGF)β1. Methods: Synovium from 10 KOA patients grouped by SFb severity was preserved for picrosirius and LH2b …


Combination Sodium Nitrite And Hydralazine Therapy Attenuates Heart Failure With Preserved Ejection Fraction Severity In A “2-Hit” Murine Model, Kyle B. Lapenna, Zhen Li, Jake E. Doiron, Thomas E. Sharp, Huijing Xia, Karl Moles, Kashyap Koul, John S. Wang, David J. Polhemus, Traci T. Goodchild, Ravi B. Patel, Sanjiv J. Shah, David J. Lefer Feb 2023

Combination Sodium Nitrite And Hydralazine Therapy Attenuates Heart Failure With Preserved Ejection Fraction Severity In A “2-Hit” Murine Model, Kyle B. Lapenna, Zhen Li, Jake E. Doiron, Thomas E. Sharp, Huijing Xia, Karl Moles, Kashyap Koul, John S. Wang, David J. Polhemus, Traci T. Goodchild, Ravi B. Patel, Sanjiv J. Shah, David J. Lefer

School of Medicine Faculty Publications

BACKGROUND: Recent studies have suggested that cardiac nitrosative stress mediated by pathological overproduction of nitric oxide (NO) via inducible NO synthase (iNOS) contributes to the pathogenesis of heart failure with preserved ejection fraction (HFpEF). Other studies have suggested that endothelial NO synthase (eNOS) dysfunction and attenuated NO bioavailability contribute to HFpEF morbidity and mortality. We sought to further investigate dysregulated NO signaling and to examine the effects of a NO-based dual therapy (sodium nitrite+hydralazine) following the onset of HFpEF using a “2-hit” murine model. METHODS AND RESULTS: Nine-week-old male C57BL/6 N mice (n=15 per group) were treated concurrently with high-fat …