Chemicals and Drugs Commons^™

Short-Term Preeclampsia Prediction: Cutoff Variations For Sflt-1/Plgf In U.S. Patients With Or Without Hypertensive Disorders, Yaxin Li, Kristen Cagino, Jim Yee, Caroline Andy, Dajana Borova, Ayush Shah, Isla Racine, Tracy Grossman, Zhen Zhao

Student Papers, Posters & Projects

BACKGROUND: Preeclampsia (PE) is a complex disorder with significant maternal and fetal risks. The soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) ratio shows promise as a diagnostic tool, but its adoption in the U.S. remains limited due to the lack of accessible testing platforms, U.S.-based studies, and evidence-based implementation guidelines.

PATIENTS/MATERIALS AND METHODS: We conducted a cohort study to evaluate the sFlt-1/PlGF ratio for predicting PE within two weeks among pregnant individuals ≥18 years, ≥20 weeks gestation. Serum samples were obtained from routine prenatal visits or triage evaluations. sFlt-1/PlGF ratios were measured using Roche Elecsys assays, and …

Semaglutide Use Before Single-Level Lumbar Fusion Associated With Fewer Readmissions And 90-Day Costs, Mitchell K. Ng, Paul G. Mastrokostas, Ariel N. Rodriguez, Abigail Razi, Leonidas E. Mastrokostas, Ahmed K. Emara, Brian T. Ford, Jacquelyn J. Xu, Jonathan Dalton, Rajkishen Narayanan, Christopher K. Kepler, Alan S. Hilibrand, Alex R. Vaccaro, Jad Bou Monsef, Afshin E. Razi

Rothman Institute Papers

CONTEXT: Semaglutide, a glucagon-like protein-1 receptor agonist used in diabetes and obesity management, has demonstrated perioperative benefits in other surgical populations. However, its role in spine surgery remains unclear.

AIMS: This study aims to evaluate whether patients undergoing single-level lumbar fusion demonstrate: (1) fewer medical complications; (2) surgical complications; and (3) healthcare utilization as measured by readmissions and costs.

SETTINGS AND DESIGN: A retrospective cohort study using a national claims database from 2010 to 2021.

SUBJECTS AND METHODS: Patients with diabetes mellitus undergoing single‑level lumbar fusion were identified and matched 1:5 using propensity scores based on age, sex, body mass …

Estrogen And Obesity Synergistically Suppress Protein S Via Hif1Α, Enhancing Thrombosis Potential, Mohammad A. Mohammad, Narender Kumar, Sonali Ghosh, Ashley L. Paysse, Claudia Leonardi, Vijaya Pilli, Ma Lorena Duhaylungsod, Eric Lazartigues, Diana Polania-Villanueva, Sadaf Nouman, Logan A. Barrios, Rima Chattopadhyay, Rafika Yasmin, Alaina Guilbeau, Manoj Kumar, Tina H. Nguyen, Jovanny Zabaleta, Li Li, Luis Del Valle M.D., Mallory T. Barbier, Samarpan Majumder, Laurent O. Mosnier, Samarpan Majumder

School of Graduate Studies Faculty Publications

Venous thromboembolism (VTE) is a leading cause of morbidity and mortality, with risk heightened in premenopausal women with obesity or use estrogen-based oral contraceptives. When both risk factors are present, the thrombosis risk increases substantially. Protein S (PS), an essential anticoagulant cofactor, is downregulated by both estrogen and obesity, but the molecular basis for this suppression remains poorly defined. We investigated the effect of estrogen and obesity on PS expression using plasma samples from 157 women stratified by BMI and contraceptive use, alongside 40 mice categorized as lean or obese with or without estrogen pellet treatment. The levels of PS …

Sulindac Sulfide Suppresses Oncogenic Transformation Through Let-7b-Mediated Repression Of K-Ras Signaling, Zhipin Liang, Ruixia Ma, Bin Yi, Adam I. Riker, Yaguang Xi

School of Graduate Studies Faculty Publications

No abstract provided.

Pathways And Challenges In The Clinical Translational Of Radiopharmaceuticals For Pediatric Investigations, Erik Stauff, Hanieh Karimi, Heidi H. Kecskemethy, Thomas H. Shaffer, Reza Vali, Lauren W. Averill, Xuyi Yue

Department of Radiology Faculty Papers

Radiopharmaceutical development and clinical translation face numerous scientific, ethical, and regulatory challenges, particularly within the pediatric population. Although molecular imaging holds significant promise for improving diagnosis and treatment across a spectrum of diseases, including pediatric-specific conditions like Kawasaki disease, autism spectrum disorders, attention-deficit/hyperactivity disorder, and neuroblastoma, the path from discovery to clinical application remains problematic. The U.S. Food and Drug Administration (FDA) provides three primary pathways-traditional Investigational New Drug (IND) applications, exploratory Investigational New Drug application (eIND), and the Radioactive Drug Research Committee (RDRC) mechanism-to facilitate clinical translation of radiotracers. However, these frameworks are not specifically tailored to pediatric needs. …

Her3 Promotes Triple-Negative Breast Cancer Progression By Upregulating Phf8 Via Mir-34b-5p-Dependent Mechanism, Hui Lyu, Cong Cong Tan, Yakun Wu, Margaret E. Larsen, Qingzhao Yu, Guobin Kang, Charles Wood, Shou Ching Tang, Bolin Liu

School of Graduate Studies Faculty Publications

Triple-negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer, with limited targeted treatment options and poor clinical outcomes. HER3 has recently emerged as a promising therapeutic target, with HER3-directed antibody–drug conjugates advancing to Phase III clinical trials for non-small cell lung cancer. However, the downstream molecular mechanisms by which HER3 promotes TNBC progression remain poorly defined. In this study, we uncovered a previously unrecognized HER3/miR-34b-5p/PHF8 signaling axis that drives TNBC cell proliferation and tumor growth. Mechanistically, HER3 activation suppresses the tumor-suppressive microRNA miR-34b-5p, resulting in the upregulation of the histone demethylase PHF8 (KDM7B), which in …

Aberrant Expression Of A Disintegrin And Metalloproteinase With Thrombospondin Motifs 13 (Adamts13) In Pancreatic Cancer Leads To Dichotomic Functions, Stephanie Allmang, Hagen R. Witzel, Anne Hausen, Simone Marquard, Christoph Eckert, Nicole Marnet, Nina Hörner, Philipp Mayer, Stefan Heinrich, Hien Dang, Wilfried Roth, Matthias M. Gaida

Department of Surgery Faculty Papers

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers characterized by highly invasive growth into the surrounding peripancreatic fat tissue, where tumor cells can directly interact with adipocytes. Due to poor response to the currently available (radio)chemotherapies, there is an urgent need for advanced therapy concepts. The present study shows that ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin motifs 13), a key factor in blood coagulation, is significantly overexpressed in human PDAC. Immunohistochemical analysis revealed that ADAMTS13 expression is associated with prolonged survival and negatively correlated with vascular density. In vitro and in vivo experiments demonstrate its partial …

Roux-En-Y Gastric Bypass Is Associated With Increased Intestinal Glucose Uptake In Humans, Florina Corpodean, Maryam Naseri, Michael Kachmar, Julia St Amant, Denis P. Blondin, Owen T. Carmichael, Vance L. Albaugh

School of Medicine Faculty Publications

CONTEXT: In animal models, Roux-en-Y gastric bypass (RYGB) is associated with increased Roux limb intestinal glucose uptake that may contribute to early metabolic benefits, though prospective clinical studies are lacking. OBJECTIVE: The present study aimed to test the hypothesis that Roux limb glucose uptake would increase relative to baseline in a cohort of patients undergoing RYGB. METHODS: RYGB patients underwent preoperative baseline, and 3- and 6-month positron emission tomography/computed tomography postoperative imaging. Maximum and mean standardized uptake values (SUV) were measured from the following predefined regions of interest: cecum, hepatic flexure, splenic flexure, sigmoid colon, duodenal bulb, Roux limb, and …

Human Kallikrein 2: A Novel Lineage-Specific Surface Target In Prostate Cancer, Fei Shen, Ryan Smith, Theresa Mcdevitt, Krista Menard, Shaozhou Tian, Gerald Chu, Ruchi Chaudhary, Jennifer Mccann, Halley Oyer, Sherry C. Wang, Steven Max, Peter Francis, William K. Kelly, Charles G. Drake

Kimmel Cancer Center Faculty Papers

PURPOSE: Targeted therapies for metastatic prostate cancer are limited, highlighting the need for novel drug targets and mechanisms of action (MoA). Human kallikrein 2 (KLK2) is a prostate-specific antigen expressed across the prostate cancer disease continuum. However, it was not recognized as a therapeutic target for prostate cancer in the past due to limited evidence of its cell surface expression. In this study, we systematically characterized KLK2 expression in prostate cancer, confirmed its cell surface expression, and demonstrated the preclinical efficacy of three KLK2-targeting therapeutics with distinct MoA.

EXPERIMENTAL DESIGN: The KLK2 expression profile in different stages of prostate cancer …

Assessing The Tumor Suppressive Impact And Regulatory Mechanisms Of Spdef Expression In Breast Cancer, Maansi Solanky, Maninder Khosla, Suresh K. Alahari

School of Graduate Studies Faculty Publications

Background/Objectives: Breast cancer is a heterogeneous disease, and the role of the transcription factor SPDEF remains controversial. We aimed to clarify the prognostic value of SPDEF, explore demographic and molecular correlates of its expression, and investigate potential regulatory mechanisms underlying its dysregulation. Methods: Genomic and clinical data for 1218 breast cancer tumors were obtained from The Cancer Genome Atlas (TCGA). SPDEF mRNA expression was compared across intrinsic subtypes, age, and race, and prognostic significance was evaluated by Kaplan–Meier analysis. Promoter methylation patterns and DNA methyltransferase (DNMT) expression were examined as potential regulatory drivers. Co-expression analysis was performed using gene panels …

Botulinum Toxin In Stiff Person Syndrome: How Useful Is It In Helping Muscle Stiffness And Spasms?, Marinos Dalakas

Department of Neurology Faculty Papers

No abstract provided.

Use Of Topical Hemostatic Agents In A Gynecologic Patient With Coagulopathy, Alexis O'Connell, Syeda Zainab Shah

HCA Healthcare Journal of Medicine

Introduction

The use of topical hemostatic agents has become common during surgical interventions. There is a wide variety of substances available to augment clotting, ranging from physical agents to topical thrombin combinations. Application of these agents in gynecologic surgery in patients with existing coagulopathies has not been studied.

Case Presentation

A 62-year-old woman with an inferior vena cava filter and a history of multiple deep vein thromboses presented to the clinic with pelvic pain, stress urinary incontinence, and uterovaginal prolapse. She underwent a total vaginal hysterectomy, sacral colpopexy, tension-free vaginal tape sling, and cystourethroscopy. Warfarin was cross titrated to enoxaparin …

Atypical Abdominal Pain: Uncovering Malignant Peritoneal Mesothelioma In Suspected Crohn's Disease: A Case Report, Catherine Loehr, Lara Boudreaux, Ann Porter Uhlhorn, Nisha Loganantharaj

School of Medicine Faculty Publications

BACKGROUND: Malignant peritoneal mesothelioma (MPM) is a rare and aggressive cancer from the serosal membranes of the abdominal cavity. In the United States, MPM accounts for about 10-15% of all mesothelioma cases, and translates into approximately 600 new cases diagnosed annually. It is typically diagnosed in Caucasian individuals, and while asbestos exposure is a well-established risk factor for pleural mesothelioma, its association with peritoneal mesothelioma remains less clear. Clinical symptoms of MPM, such as abdominal pain, bloating, and weight loss, overlap with other gastrointestinal disorders, which often leads to delayed diagnosis. This case report presents a unique instance of MPM …

Managing Anticoagulation In A Patient With Calciphylaxis And Mechanical Valve: A Therapeutic Dilemma, Qutaiba Qafisheh, Abdalhakim Shubietah, Mohanad Qwaider, Muath A. Baniowda, Abdalrahman Assaassa, Roaa Aljunaidi, Abubakar Nazir

Division of Cardiology Faculty Papers

BACKGROUND: Calciphylaxis is a rare, life-threatening vasculopathic syndrome most commonly seen in end-stage renal disease (ESRD) and associated with high mortality. Vitamin K antagonists complicate management in patients with mechanical valves by potentially exacerbating vascular calcification while remaining essential for thromboprophylaxis.

CASE PRESENTATION: A 50-year-old woman with ESRD on hemodialysis and a mechanical mitral valve on warfarin presented with severe abdominal pain and rapidly progressive necrotic ulcers. Despite broad-spectrum antibiotics and sodium thiosulfate, lesions worsened. Biopsies were nondiagnostic; however, the clinical phenotype was consistent with calciphylaxis. A multidisciplinary team transitioned anticoagulation from warfarin to subcutaneous unfractionated heparin (UFH) (333 U/kg …

Cd5 Expression In Ctcl And Its Implications For Anti-Cd5 Car T-Cell Therapy, Leena Wardeh, Madeline Williams, Courtney Prestwood, Zachary Wolner, Neda Nikbakht

Department of Dermatology and Cutaneous Biology Faculty Papers

Cutaneous T-Cell Lymphomas (CTCL) are a heterogenous group of T-cell malignancies in the skin and have poor treatment outcomes in advanced stages. CD5, a surface glycoprotein expressed on most mature T cells, has emerged as a promising target for chimeric antigen receptor (CAR) T-cell therapy in systemic T-cell lymphomas. However, its expression profile in CTCL and relevance for targeted therapy remain unclear. Notably, in CTCL, the cell surface expression of receptors, such as CD7 and CD26, tends to become downregulated on the surfaces of malignant T cells In this study, we analyzed single-cell RNA sequencing (scRNA-seq) data from patients at …

Predicting Intravitreal Treatment Response Using Ultrawide-Field Angiographic Biomarkers In Diabetic Retinopathy, Karthik Reddy, Callie Deng, Boonkit Purt, Yue Liang, Nikhil Bommakanti, Gina Yu, Julie Rosenthal, Yannis M. Paulus

Wills Eye Hospital Papers

BACKGROUND: Diabetic retinopathy (DR) is a sight-threatening retinal disease with pathological mediation by vascular endothelial growth factor (VEGF). Intravitreal anti-VEGF injections are commonly used to manage DR. Ultra-wide-field fluorescein angiography (UWF-FA) can assess DR severity and characterize the amount of non-perfused retina (non-perfusion area, NP), neovascularization (neovascular area, NV), and foveal avascular zone (FAZ). However, the association between anti-VEGF treatment and NP, NV, and FAZ characterized by UWF-FA is not well established.

METHODS: A retrospective, single-center cohort study involved eyes of patients with Type 1 or 2 diabetes mellitus with at least one UWF-FA image. The area of the FAZ, …

Regorafenib Pulmonary Toxicity: A Case Of Cavitary Lung Disease And Ards Treated With Infliximab, Michael Dong, Mackenzie Kramer, Tanmay Gandhi, Gautam George

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

Regorafenib-induced pneumonitis and acute respiratory distress syndrome (ARDS) are rare and poorly characterized toxicities. We describe a 43-year-old male with metastatic colorectal cancer who developed hypoxic respiratory failure after two cycles of regorafenib. Imaging revealed cavitary lung lesions and diffuse ground glass opacities. Despite antibiotics and high-dose corticosteroids, his condition deteriorated, requiring ICU admission and mechanical ventilation. Bronchoalveolar lavage revealed bacterial pathogens, and he was treated for pneumonia. After multidisciplinary discussion, he was assessed to have regorafenib-induced pneumonitis as a major driver of his respiratory failure, and after limited steroid response, infliximab was administered with marked respiratory improvement. However, he …

Glucagon-Like Peptide 1 Receptor Agonists And The Clinical Outcomes Of Inflammatory Bowel Disease: A Systematic Review And Meta-Analysis, Ahmed B. Bayoumy, Lindsay M. Clarke, Parakkal Deepak, Aakash Desai, Priya Sehgal, Uri Gorelik, Haggai Bar-Yoseph, Marie Villumsen, Chris J. J. Mulder, Dirk J. Stenvers, Maarten E. Tushuizen, Nanne K. H. De Boer

Division of Gastroenterology and Hepatology Faculty Papers

BACKGROUND: Prior studies showed worse outcomes in obese inflammatory bowel disease (IBD) patients, especially those related to hospitalizations, surgery, and steroid-free remission. Glucagon-like peptide-1 receptor agonists (GLP1-RAs) have demonstrated significant metabolic benefits for patients with type 2 diabetes mellitus (T2DM) and obesity. Hence, GLP1-RAs may improve clinical outcomes in patients with IBD, especially those with obesity. The objective was to systematically evaluate the impact of GLP1-RAs on clinical outcomes in patients with IBD.

METHODS: A comprehensive literature search was performed using the databases PubMed, Embase, Web of Science, and Cochrane Library from inception to March 15, 2025. Studies reporting outcomes …

A Plain Language Summary Publication Of Patients’ Survival With Endometrial Cancer Treated With Dostarlimab Plus Carboplatin-Paclitaxel, Matthew A. Powell, Line Bjørge, Lyndsay Willmott, Zoltán Novák, Destin Black, Lucy Gilbert, Sudarshan Sharma, Giorgio Valabrega, Lisa M. Landrum, Martina Gropp-Meier, Ashley Stuckey, Ingrid Boere, Michael A. Gold, Yakir Segev, Sarah E. Gill, Christine Gennigens, Alexandra Sebastianelli, Mark S. Shahin, Bhavana Pothuri, Bradley J. Monk, Joseph Buscema, Robert L. Coleman, Brian M. Slomovitz, Kari L. Ring, Thomas J. Herzog, Morad Marco Balas, Matthew Grimshaw, Shadi Stevens, Dominic W. Lai, Carolyn Mccourt, Mansoor Raza Mirza

Abington Jefferson Health Papers

What is the purpose of this PLS-P? The purpose of this plain language summary of publication is to help you understand recent findings from Part 1 of the RUBY study (full name ENGOT-EN6/GOG3031/RUBY trial). • Researchers sometimes study new combinations of already approved individual treatments to see if the combinations work well together and if they are safe to prescribe to patients. • In Part 1 of the RUBY study, the combination of dostarlimab with carboplatin-paclitaxel was investigated to see how well it worked for patients with primary advanced or recurrent endometrial cancer when compared with patients who were given …

Effectiveness Of Vitamin D3 In Facilitating The Therapeutic Progression Of Healing Diabetic Foot Ulcers, Fatemeh Nouri, Sara Aghaei, Gülüzar Özbolat, Yusuf Döğüş, Mahdi Mirhamidi, Reza Rahimi Barghani, Amin Daemi

Chulalongkorn Medical Journal

Background: Today’s, diabetes and its complications have afflicted a large population all over the world, so that it is estimated that its prevalence in all age groups will reach from 2.8% in 2000 to 4.4% in 2030. It is well known that vitamin D may cause rapid wound healing and anti-inflammatory.

Objective: Regarding the importance of the quality of life of diabetic patients and the improvement of chronic diabetic foot ulcers, this paper aims to investigate the efficacy of vitamin D3 on the healing of diabetic foot ulcers. The present research is conducted as a randomized controlled trial.

Methods: …

Concurrent Local Therapy Extends Clinical Benefit Of Tebentafusp In Metastatic Uveal Melanoma Patients, Tristan L. Lim, Kamaneh Montazeri, Eric Wehrenberg-Klee, Antoine Desilets, Rino S. Seedor, Marlana Orloff, Takami Sato, Michael Caplan, Mariam El-Ashmawy, Benjamin Izar, Shaheer Khan, Inderjit Mehmi, Aleigha Lawless, Theodore S. Hong, Omid Hamid, Richard D. Carvajal, Alexander Shoushtari, Ryan J. Sullivan

Kimmel Cancer Center Faculty Papers

BACKGROUND: Tebentafusp has significantly improved overall survival in HLA-A*02:01+ metastatic uveal melanoma (mUM) patients even in those with a best objective response of progressive disease. Thus, strategies to maintain tebentafusp therapy are critical. Here, we examine the efficacy and safety of adding concurrent local therapy (CLT) to tebentafusp upon radiological progression with tebentafusp alone.

PATIENTS AND METHODS: This multicenter retrospective study included mUM patients treated with tebentafusp and CLT, consisting of extrahepatic soft tissue irradiation and liver-directed therapies (LDTs). Efficacy of target and nontarget sites were assessed per RECIST version 1.1. PFS with tebentafusp alone (PFS1) was compared to that …

Ketorolac Use Following Operative Clavicle Fracture Fixation Is Not Associated With Increased Nonunion Or Surgical Complications: A Propensity-Matched Analysis, Tuckerman Jones, Tej Joshi, Akhil Katakam, Daniella Ogilvie, Sefy Paulose, Balazs Galdi

Wills Eye Hospital Papers

OBJECTIVES: Nonsteroidal anti-inflammatory drugs (NSAIDs), including ketorolac, are commonly used for postoperative pain management. Concerns about their potential impact on bone healing have been raised. This study investigated the relationship between ketorolac use and postoperative complications following clavicle surgery, including nonunion rates.

METHODS: This retrospective cohort study used the TriNetX Research Database to identify patients who underwent surgical fixation of clavicle fractures between 2002 and 2022. Two propensity-matched cohorts were created: patients who received postoperative ketorolac and those who did not. Primary outcomes included nonunion diagnosis and revision surgery; secondary outcomes included opioid use, wound disruption, surgical site infection, and …

Non-Invasive Detection Of Choroidal Melanoma Via Tear-Derived Protein Corona On Gold Nanoparticles: A Machine Learning Approach, Hakimeh Rakhshandeh, Ahmad Nasiraei, Hamid Riazi-Esfahani, Babak Masoomian, Fariba Ghassemi, Mojtaba Arjmand, Saeed Heidari Keshel, Fatemeh Atyabi, Rassoul Dinarvand

Wills Eye Hospital Papers

This study investigates the feasibility of using tear sample analysis, based on protein corona formation on gold nanoparticles combined with electrospray ionization mass spectrometry (ESI-MS) and machine learning techniques, as a non-invasive approach for the detection of choroidal melanoma. The aim is to assess whether protein-nanoparticle interactions can support early and reliable identification of this ocular condition. Tear samples were collected using Schirmer strips from six healthy individuals and six patients diagnosed with choroidal melanoma, with subsequent augmentation to 18 samples per group. Gold nanoparticles (AuNPs, ~ 20 nm) were synthesized via citrate reduction and incubated with tear samples to …

Inflammation And Detection: Rethinking The Biomarker Landscape In Gastric Cancer, Keykavous Parang, Koosha Paydary

Pharmacy Faculty Articles and Research

Gastric carcinoma is a leading cause of cancer-related mortality worldwide, yet reliable noninvasive biomarkers for its early detection remain limited. As research continues to elucidate the inflammatory underpinnings of tumor initiation and progression, it has become increasingly clear that pro-inflammatory cytokines may hold promise as diagnostic adjuncts. Serum cytokines such as interleukin (IL)-1β, IL-6, IL-8, and interferon-gamma have been frequently reported as elevated in gastric cancer patients compared to healthy individuals. These molecules, known for their roles in modulating tumor-promoting inflammation, angiogenesis, and immune evasion, may serve as accessible indicators of disease presence or progression. Several studies have shown that …

Monitoring The Hematologic Markers In Patients Undergoing Single-Stage Exchange Arthroplasty For Periprosthetic Joint Infection, Wenbo Mu, Juan D. Lizcano, Boyong Xu, Wentao Guo, Abudousaimi Aimaiti, Xiaogang Zhang, Javad Parvizi, Li Cao

Rothman Institute Papers

BACKGROUND: Periprosthetic joint infection (PJI) is a serious complication that necessitates a complex treatment strategy. Single-stage exchange arthroplasty, combined with intravenous and intra-articular antibiotic infusions, has shown high efficacy in treating complex PJIs. However, the impact of this approach on hematologic parameters remains underexplored. This study aims to evaluate the postoperative trends in blood platelet count, white blood cell (WBC) count, and neutrophil count in patients undergoing single-stage exchange arthroplasty.

METHODS: A retrospective analysis was conducted on 313 patients who underwent single-stage revision for PJI between June 2010 and October 2022. Hematologic parameters were monitored for the first seven postoperative …

Ybx1-Mediated Activation Of Srebp2 Drives Sorafenib Resistance Via Cholesterol Biosynthesis In Hepatocellular Carcinoma, Veerababu Nagati, Dennis Kwabiah, Yamile Abuchard, Ana Ayala Pazzi, Shaibir Hussain, Salique H. Shaham, Manish Tripathi

Research Colloquium

Background: Hepatocellular carcinoma (HCC) is an aggressive, largely chemo-resistant cancer with a poor prognosis and is the leading cause of cancer-related deaths worldwide. Currently, there is no effective systemic chemotherapy for HCC. Sorafenib is a multikinase inhibitor commonly used as the first-line treatment for advanced HCC. However, acquired drug resistance significantly limits its clinical effectiveness. The Y-box binding protein (YBX1) is an oncogenic RNA-binding protein found to be upregulated in sorafenib-resistant HCC cells and tissues.

Methods: HCC model SK Hep1, YBX1 overexpression, and knockdown cells were prepared by transient transfection with puromycin selection, and stable cell lines were established through …

Corticobasal Syndrome With Mixed Pathology In The Absence Of Grn Mutation: A Clinico-Pathological Case Of Ftld-Tdp With Coexisting Alzheimer’S And Lewy Body Pathology, Hugo Zamarron, David Irwin, Jeffery Phillips, Edward Lee, Matthew Tisdall, Corey Mcmillan

Research Colloquium

Background: Corticobasal syndrome (CBS) is a neurodegenerative disorder characterized by often asymmetric fronto-pariteal and extra-pyramidal features that is traditionally associated with tauopathy, but pathological findings are heterogenous, including other forms of frontotemporal lobar degeneration (FTLD) and mixed pathologies of aging. We present clinical, radiographic, and histopathologic features of asymmetry in a unique patient with CBS and underlying FTLD with TDP-43 pathology (FTLD-TDP), co-occurring with other age-related pathologies.

Case Presentation: A 76-year-old man presented with progressive cognitive and motor dysfunction including asymmetric parkinsonism, left-sided dystonia and rigidity, apraxia, visuospatial impairment, and a subtle social disorder including apathy and social withdrawal. The …

Efficacy And Safety Of Rigosertib In Patients With Recessive Dystrophic Epidermolysis Bullosa-Associated Advanced/Metastatic Cutaneous Squamous Cell Carcinoma, Martin Laimer, Andrew P. South, Elisabeth Mayr, Sophie Kitzmueller, Lauren Banner, Michael Alexander, Linda Hosler, Henry Yang, Matthew Parris, Meena Arora, Georg Zimmermann, Gregor Schweighofer-Zwink, Johann Bauer, Neda Nikbakht

Department of Dermatology and Cutaneous Biology Faculty Papers

BACKGROUND: Recessive dystrophic epidermolysis bullosa (RDEB) is an epithelial fragility disease primarily affecting the skin and is caused by variants in the COL7A1 gene. Individuals with RDEB are predisposed to develop highly aggressive cutaneous squamous cell carcinomas (SCCs) which are the most common cause of premature death. There is a lack of effective prevention or treatment options for patients with RDEB-SCC.

OBJECTIVES: To evaluate the antitumour activity and safety of the polo-like kinase-1 (PLK1) inhibitor, rigosertib, two investigator-initiated open-label, single-arm phase II studies were opened in Europe and the USA and enrolled five patients with RDEB diagnosed with locally advanced …

Bard1: A Friend Or Foe In Pancreatic Ductal Adenocarcinoma?, Lily Zekavat, Aditi Jain

Department of Surgery Faculty Papers

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive solid malignancy with poor overall prognosis and limited response to standard treatments. Growing interest in the modulation of DNA repair mechanisms, including the homologous recombination (HR) repair pathway, has opened new avenues for therapeutic development. BARD1 (BRCA1-Associated RING Domain 1) plays a complex role in tumor biology, functioning either as a tumor suppressor or as an oncogenic driver, depending on isoform expression, cellular context, and regulatory environment. In this review, we examine the dual roles of BARD1, focusing on its regulation and paradoxical activities in PDAC. We summarize evidence that BARD1 and BARD1 …

Distinct Transcriptional Regulation Of The Wnt And Tgfβ Signaling Families Associated With Wound Healing And Fibrotic Outcomes To Lens Injury, Catherine Lalman, Kylie R. Stabler, Joshua Disatham, Lisa A. Brennan, Marc Kantorow, Janice L. Walker

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Posterior capsule opacification (PCO) is a fibrotic complication of cataract surgery caused by aberrant repair of residual lens cells. It remains unclear how the lens injury response shifts toward a pathological repair process. Here, we performed a transcriptional analysis of two major pro-fibrotic pathways, the TGF-β superfamily and Wnt signaling pathways to determine how they are differentially regulated during regenerative wound healing versus fibrosis in a lens injury model. For these studies, RNA sequencing was performed on an ex vivo lens explant system that models post-surgical healing within regenerative and fibrotic microenvironments, from 0 to 3 days post-injury. Fibrotic conditions …