Diseases Commons^™

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 …

Predictors Of All-Cause In-Hospital Mortality In Patients With Malignant Well-Differentiated Gastroenteropancreatic Neuroendocrine Tumors, Elvis Obomanu, Tarfa Verinumbe, Tinsae Anebo, Colton Jones, Claudia Dourado

Einstein Health Papers

BACKGROUND: Factors influencing in-hospital mortality in patients with well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs) remain understudied, highlighting gaps in optimizing acute clinical outcomes. This study aimed to identify sociodemographic and clinical predictors of all-cause in-hospital mortality in this population.

METHODS: Using 2016 - 2020 data from the National Inpatient Sample (NIS), patients with malignant well-differentiated GEP-NETs were identified via the International Classification of Diseases, 10th Revision (ICD-10) codes. The primary outcome was in-hospital mortality. Sociodemographic and clinical variables (heart failure (HF), malnutrition, Charlson Comorbidity Index (CCI), and tumor site) were analyzed using multivariable logistic regression.

RESULTS: Among 5,642 patients (mean age …

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 …

Artificial Intelligence In Head And Neck Cancer: Towards Precision Medicine., Jacob Hagen, Logan Hornung, William Barham, Supratik Mukhopadhyay, Ada Bess, Kevin Contrera, Kevin Contrera, Devraj Basu, Vlad Sandulache, Guillaume Spielmann, Sagar Kansara

School of Medicine Faculty Publications

Simple Summary: This review was conducted to highlight current and potential applications of artificial intelligence (AI) in the care of patients with head and neck cancer, the barriers to its clinical implementation, and the relative scarcity of research in this field. While AI has demonstrated success in other areas of oncology, its role in head and neck cancer remains limited, with progress slowed by technical, ethical, and logistical challenges. Nevertheless, integrating AI with multiomics approaches presents a promising opportunity to advance precision medicine in this patient population. The findings presented in this manuscript may encourage further multi-institutional studies aimed at …

Artificial Intelligence In Head And Neck Cancer: Towards Precision Medicine, Jacob Hagen, Logan Hornung, William Barham, Supratik Mukhopadhyay, Adam Bess, Kevin Contrera, Devraj Basu, Vlad Sandulache, Guillaume Spielmann, Sagar Kansara

School of Medicine Faculty Publications

Over the past 20 years, the capabilities of artificial intelligence (AI) have gained significant interest. While AI has been implemented to various degrees in several disciplines, its unique applications in head and neck cancer (HNC) remain underdeveloped. This narrative review examines the existing body of literature regarding the use of AI in HNC. Studies to date have demonstrated AI’s utility across multiple phases of the HNC treatment continuum. Despite its promise, integrating AI into clinical practice faces several challenges, including concerns about system integrity, generalizability, privacy, and bias. In this review, we address these challenges and offer insights into future …

Nevus Sebaceous Of Jadassohn With Secondary Cystic Papillary Hidradenoma, Jordan A. Book, Rosemary Prejean, Jonathan M. Joseph, Nicholas Culotta, Christopher Haas

School of Medicine Faculty Publications

Nevus sebaceous of Jadassohn (NS) is a congenital cutaneous hamartoma that typically presents at birth as a plaque on the face, scalp, or neck. While NS is associated with a risk of neoplastic transformation, the majority of secondary tumors are benign, with the most common being trichoblastomas and syringocystadenomas. In this report, we present a rare case of a 63-year-old male with a right parietal scalp NS with a secondary cystic papillary hidradenoma (HP), which is a benign tumor that almost exclusively occurs in the perineal region. Histopathologic examination was consistent with NS, revealing hyperkeratosis, parakeratosis, increased sebaceous glands, ectopic …

A Novel Sialylation Pathway Mediated By Extracellular Vesicles In Aggressive Prostate Cancer, Camila A. Bach, Md Niamat Hossain, Ishan J. Chaudhari, Cecilia E. Verrillo, Nicole M. Naranjo, Isabella Amoroso, Anna Testa, Samuel Sey, W. Kevin Kelly, Susan L. Bellis, Aurelio Lorico, Ada G. Blidner, Gabriel A. Rabinovich, Lucia R. Languino

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Altered cell surface glycosylation is a hallmark of cancer; among aberrant glycan structures, hypersialylated proteins contribute to disease progression. The enzyme ST6 β-galactoside α2,6-sialyltransferase 1 (ST6GAL1) mediates α2,6-linked sialylation of N-glycosylated proteins and is upregulated in many cancers, including prostate cancer (PrCa). We propose that ST6GAL1 may be released by cancer cells in small extracellular vesicles (sEVs) in the PrCa tumor microenvironment to potentially modulate cell surface sialylation in recipient cells. We isolated sEVs from PrCa cells by density gradient separation and characterized them by nanoparticle tracking analysis using ZetaView and immunoblotting analysis. We identified ST6GAL1 in both its membrane-bound …

Subtype-Specific Her3 Enrichment In Basal-Like Breast Cancer Is Regulated Via The Gata2/Gata3–Foxa1 Axis, Congcong Tan, Hui Lyu, Sanbao Ruan, Yakun Wu, Margaret E. Larsen, Shou Ching Tang, Bolin Liu

School of Medicine Faculty Publications

Basal-like breast cancer (BLBC) is a major subtype of triple-negative breast cancer (TNBC), characterized by aggressive behavior, limited treatment options, and poor prognosis. While HER3 overexpression is frequently observed in TNBC and associated with poor outcomes, its subtype-specific expression and therapeutic potential remain unclear. Here, we demonstrated that HER3 signaling is selectively hyperactivated in BLBC compared to claudin-low breast cancer (CLBC) using transcriptomic profiling. Histone deacetylase inhibitors (HDACi), Romidepsin and Panobinostat, exerted potent antitumor effects on BLBC by selectively downregulating HER3 expression. HER3 levels were positively correlated with FOXA1, a key transcriptional activator. Mechanistically, we identified GATA2 and GATA3 as …

Diagnostic Journey In The Recognition Of Oncogenic Osteomalacia, Steven B. Nagelberg, Mihaela Biscoveanu, Barbara Bix, Carrie Andrews, Srinivas Prasad

Jefferson Health - Northeast Papers (formerly Aria Health Papers)

A 73-year-old woman with a remote history of successfully treated primary hyperparathyroidism was referred to our office because of multiple skeletal fractures and proximal muscle weakness. Prior laboratory evaluation demonstrated hypocalcemia, vitamin D deficiency, elevated PTH, and elevated alkaline phosphatase. Updated evaluation in our clinic additionally showed hypophosphatemia prompting measurement of serum fibroblast growth factor 23 (FGF23). FGF23 proved to be markedly elevated prompting consideration of tumor-induced osteomalacia. Positron emission tomography with Cu-64 oxodotreotide revealed an enhancing focus in the left thoracic spine that was confirmed on magnetic resonance imaging to be a 1.5-cm extradural mass. The patient underwent surgical …

The Role Of Liver Macrophages In Viral Liver Pathogenesis, Alexis Brantly, Kyle Yeakle, Michael J. Bouchard, Peter J. Gaskill, Michael R. Nonnemacher

Kimmel Cancer Center Faculty Papers

Liver macrophages play important roles in the pathophysiology of liver fibrosis and hepatocellular carcinoma. However, liver macrophages are a heterogenous population and have differing roles in maintenance of liver function and response in disease. In a healthy liver, macrophages play a critical role in antigen processing, maintaining tolerance to the high levels of gut-derived bacterial products, and regulating inflammation through cytokine response. However, macrophages also play a critical role in liver pathology, specifically in the context of viral infection. The liver is targeted by multiple viruses, including human immunodeficiency virus, hepatitis B virus, and hepatitis C virus, which dysregulate macrophage …

Unplanned Hospitalization Among Advanced Prostate Cancer Patients By Diabetes Status: A Population-Based Study, Amy L. Shaver, Krupa Gandhi, Scott W. Keith, Nikita Nikita, Christopher C. Yang, Felix J. Kim, Hushan Yang, William K. Kelly, Stephen J. Freedland, Grace Lu-Yao

Kimmel Cancer Center Faculty Papers

BACKGROUND: Older adults with advanced prostate cancer and type 2 diabetes mellitus are underrepresented in trials of androgen receptor pathway inhibitors. This study examined changes in unplanned hospitalization rates in patients receiving androgen receptor pathway inhibitors by type 2 diabetes mellitus status and assessed if unplanned hospitalization varies according to androgen receptor pathway inhibitors.

METHODS: This population-based study of advanced prostate cancer patients aged older than 66 years used Surveillance, Epidemiology, and End Results-Medicare data. Prepost androgen receptor pathway inhibitor initiation changes and androgen receptor pathway inhibitor differences in unplanned hospitalization rates were estimated by adjusted incidence rate ratio with …

Risk Of Second Primary Lung Cancer Among Cancer Survivors Stratified By The Site Of First Primary Cancer And The Lung Cancer Screening Eligibility Status, Sara Nofal, Edwin J Ostrin, Jianjun Zhang, Jia Wu, Paul Scheet, Mara B Antonoff, John V Heymach, Iakovos Toumazis

Faculty, Staff and Student Publications

Personal history of cancer is an independent risk factor for developing lung cancer. However, it is not considered in the current US lung cancer screening (LCS) guidelines. In this study, we assessed the risk of developing lung cancer among cancer survivors across 24 different sites of first primary cancer stratified by their LCS eligibility status. Using data from the Patient History Database at the University of Texas MD Anderson Cancer Center, we calculated and compared the cumulative incidence of second primary lung cancer, the overall and the LCS eligibility status-specific, stratified by the site of first primary cancer among cancer …

Educational Point-Of-Care Ultrasound Discovers Adrenal Cortical Carcinoma, A Case Report: Clinical Implications And Review Of The Literature, Minh Q. Nguyen, Moshe Bengio, Vu H. Tran

HCA Healthcare Journal of Medicine

Introduction

Point-of-care ultrasound (POCUS) has become an indispensable tool for emergency physicians in assessing intra-abdominal pathology due to its real-time visualization, portability, and cost-effectiveness. While POCUS is not traditionally focused on adrenal gland assessment, incidental findings of adrenal masses during examinations have been reported. Our patient presented with a chronic obstructive pulmonary disease (COPD) exacerbation and was found to have a large adrenal mass, discovered incidentally, during thoracic ultrasound.

Case Presentation

This case report presents the discovery of an adrenal mass in a patient with respiratory distress due to a COPD exacerbation, emphasizing the importance of sonographers’ ability to identify …

Should We Subtype Gastric Intestinal Metaplasia In Gastric Biopsies, A Single Institution's Experience, Haibo Wang, Yu Liu, Asra Feroze, Zengying Wu, Jonathan D. Somma, Zhiyan Fu

School of Medicine Faculty Publications

Gastric intestinal metaplasia (GIM) is considered a risk factor for gastric dysplasia and adenocarcinoma. While surveillance endoscopies are often performed, particularly for incomplete GIM, the clinical value of histologic subtyping (complete, incomplete, or mixed) remains unclear. This study evaluated the progression risk of different GIM subtypes diagnosed through random gastric biopsies and their association with various clinical factors. Archived pathology data from 206 gastric biopsy cases were analyzed, including 52 negative controls, 56 complete GIM, 54 incomplete GIM, and 44 mixed GIM. Histologic slides were reviewed for subtype confirmation and other pathological changes; clinical data were extracted from medical records. …

Oncogenic Effects Of Ecm Remodeling In Obesity And Breast Cancer, Mackenzie L. Hawes, Marcus A. Moody, Caroline R. Mccauley, Abigail G. Huddleston, Maansi Solanky, Dara H. Khosravi, Ayushi R. Patel, Ronald M. Lynch, Suresh K. Alahari, Bruce A. Bunnell, Jorge A. Belgodere, Van T. Hoang, Matthew E. Burow, Elizabeth C. Martin

School of Medicine Faculty Publications

Extracellular matrix (ECM) components are key regulators in breast cancer progression, as ECM remodeling is essential for breast cancer cells to invade into surrounding tissue. This process is characterized by the alignment of fibrillar collagens, breakdown of basement membrane components, and increased interstitial collagen stiffness. In patients with obesity, pre-existing ECM changes, including excessive collagen deposition and heightened matrix stiffness, mimic alterations detected in breast cancer. Given that obesity is a predictor of poor prognosis and resistance to treatment in breast cancer, it is crucial to understand how ECM conditioned by obesity affects disease outcomes. In this review, we highlight …

Human Interpretable Grammar Encodes Multicellular Systems Biology Models To Democratize Virtual Cell Laboratories, Jeanette A I Johnson, Daniel R Bergman, Heber L Rocha, David L Zhou, Eric Cramer, Ian C Mclean, Yoseph W Dance, Max Booth, Zachary Nicholas, Tamara Lopez-Vidal, Atul Deshpande, Randy Heiland, Elmar Bucher, Fatemeh Shojaeian, Matthew Dunworth, André Forjaz, Michael Getz, Inês Godet, Furkan Kurtoglu, Melissa Lyman, John Metzcar, Jacob T Mitchell, Andrew Raddatz, Jacobo Solorzano, Aneequa Sundus, Yafei Wang, David G Denardo, Andrew J Ewald, Daniele M Gilkes, Luciane T Kagohara, Ashley L Kiemen, Elizabeth D Thompson, Denis Wirtz, Laura D Wood, Pei-Hsun Wu, Neeha Zaidi, Lei Zheng, Jacquelyn W Zimmerman, Jude M Phillip, Elizabeth M Jaffee, Joe W Gray, Lisa M Coussens, Young Hwan Chang, Laura M Heiser, Genevieve L Stein-O'Brien, Elana J Fertig, Paul Macklin

Faculty, Staff and Student Publications

Cells interact as dynamically evolving ecosystems. While recent single-cell and spatial multi-omics technologies quantify individual cell characteristics, predicting their evolution requires mathematical modeling. We propose a conceptual framework-a cell behavior hypothesis grammar-that uses natural language statements (cell rules) to create mathematical models. This enables systematic integration of biological knowledge and multi-omics data to generate in silico models, enabling virtual "thought experiments" that test and expand our understanding of multicellular systems and generate new testable hypotheses. This paper motivates and describes the grammar, offers a reference implementation, and demonstrates its use in developing both de novo mechanistic models and those informed …

Silvestrol Inhibits Nasopharyngeal Carcinoma Cells And Synergizes With Cx‑5461: Insights From A Proteomics Study, Maelinda Daker, Munirah Ahmad, Alan Khoo, Lu Ping Tan, Siok-Fong Chin, Siaw San Hwang, Paul Neilsen

Department of Medical Oncology Faculty Papers

Nasopharyngeal carcinoma (NPC) is a cancer arising from the epithelial cells of the nasopharynx, which is rare in Western countries but extremely prevalent in Borneo and the Southern China region. Present-day hurdles in NPC treatment that lead to poor quality of life and poor survival include distant metastasis and resistance to chemoradiotherapy. Silvestrol and its 5'''-epimer, episilvestrol, are compounds isolated from the plant Aglaia stellatopilosa, which is endemic to Borneo. Silvestrol, a protein synthesis inhibitor, preferentially inhibits the translation of cancer-associated mRNAs. CX-5461 is an inhibitor of RNA polymerase I that catalyzes rRNA synthesis. The present study sought to …

Beyond Smoking: A Geospatial Investigation Of Factors Associated With Lung And Bronchus Cancer Risk In Pennsylvania, Tesla D. Dubois, Daniel Wiese, Kevin A. Henry, Shannon M. Lynch

Kimmel Cancer Center Faculty Papers

INTRODUCTION: While smoking is the leading cause of lung and bronchus cancer (LBC), additional exposures have been implicated and may explain the rise in LBC among never-smokers. To better understand the spatial distribution of LBC incidence and associated risk factors, this study aims to identify geographic areas with significantly elevated incidence rates in Pennsylvania and investigate the potential underlying risk factors.

METHODS: Using cancer registry data aggregated to the census tract level, spatial scan statistics were applied to detect areas of higher-than-expected LBC incidence across the state. Associations were then tested between census tract inclusion in a high-incidence area and …

Radiologic Findings Of A Mediastinal Mass With Pleural Fluid Cytologic Analysis: A Case Report Of Recurrent Mantle-Cell Lymphoma, Mark Cwajna, Zaain Ahmad, Evan Basha, Emily Maggioncalda, Shehbaz Ahmad, Joel Thompson

Advances in Clinical Medical Research and Healthcare Delivery

This case report details a 69-year-old male who presented with a right-sided pleural effusion and a mediastinal mass that was ultimately identified as recurrent mantle-cell lymphoma, occurring over 20 years after his initial diagnosis. Imaging findings discussed include chest radiograph and chest, abdomen and pelvis computed tomography depicting the mass compressing on various neighboring structures.

Radiologic Evaluation And Management Of Metastatic Renal Cell Carcinoma With Tumor Thrombus Extension Into Right Atrium, Zaain Ahmad, Mark Cwajna, Evan Basha, Adithya Bala, Joel Thompson

Advances in Clinical Medical Research and Healthcare Delivery

This case report discusses the radiologic evaluation, histopathology, and management of a 67-year-old female with metastatic renal cell carcinoma (RCC) extending as a tumor thrombus into the right atrium. The patient had newly developed hematuria that was not followed up with the recommended imaging modality. Months later, the patient presented to the emergency department with progressive hematuria in addition to symptoms of dyspnea and significant weight loss. Initial CT imaging revealed a large renal mass with metastasis to the liver and lungs, along with tumor thrombus invading the inferior vena cava and right atrium. Histopathologic evaluation confirmed metastatic RCC and …

Associations Between Social Drivers Of Health And Breast Cancer Stage At Diagnosis Among U.S. Black Women, Mollie Barnard, Bo Qin, Marc Emerson, Etienne Holder, Matthew Dunn, Shromona Sarkar, Nuo Xu, Yutong Li, Christine Ambrosone, Elisa Bandera, Julie Palmer, Melissa Troester, Terry Hyslop

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

U.S. Black women have disproportionately high breast cancer mortality, partly due to later-stage diagnoses. We examined how social drivers of health (SDOH) relate to stage at diagnosis by analyzing data from 4,995 breast cancer survivors in the Black Women's Health Study, Carolina Breast Cancer Study, and Women's Circle of Health Studies. SDOH were self-reported and stage was ascertained from medical records. We used polytomous logistic regression to estimate odds ratios (ORs) for diagnosis at stages III/IV or II versus stage I (referent), adjusting for age, insurance status, and income. Meta-analyzed results indicated that underutilization of screening mammography (OR = 3.21, …

Nuak Kinases: Signaling Mechanisms And Therapeutic Applications, Nicole M. Cullen, Peter Rosston, Bakhtawar Tufail, Anne E. D'Armond, Ayushi Patel, Dara H. Khosravi, Bridgette M. Collins-Burow, Van T. Hoang, Elizabeth C. Martin, David H. Drewry, Matthew E. Burow, Suresh K. Alahari

School of Medicine Faculty Publications

The novel (nua) kinases 1 and 2 are two of 12 AMP-activated protein–related kinases whose signaling pathways are involved in cancer progression, as well as neurologic, fibrotic, and inflammatory diseases. Currently, there are 80 Food and Drug Administration-approved kinase inhibitors which target roughly 24 of the 500+ known human kinases, leaving most kinases underexplored, including NUAK1 and NUAK2. Thus, there is a critical need for selective inhibition of NUAK1 and NUAK2 signaling. Here, we review the protein structure, known upstream regulators and downstream targets, and expression profiles of NUAK1 and NUAK2 in cancerous compared to noncancerous tissue. We also delineate …

Breast Cancer Survival Rates And Determinants In Ethiopia: A Systematic Review And Meta-Analysis Of Longitudinal Studies, Abenezer M. Tafese, Meseker T. Fentie, Beminate L. Seifu, Angwach A. Asnake, Bikiltu D. Dirbaba, Abdisa G. Jara, Elsabeth Tizazu Asare, Brandon George

College of Population Health Faculty Papers

BACKGROUND: Breast cancer is the most common cancer and the leading cause of cancer mortality among women in Ethiopia, accounting for 32% of new cancer cases and 17.6% of cancer deaths. Despite its growing burden, comprehensive data on survival rates and contributing factors remain limited. This systematic review and meta-analysis aimed to synthesize existing data on breast cancer survival in Ethiopia and identify key determinants influencing outcomes.

METHODS: A comprehensive systematic search was conducted in PubMed, Web of Science, Scopus, Embase, and CINAHL to identify studies on breast cancer survival in Ethiopia published between January 2014 and August 2024. Eligible …

Efficacy Of Infliximab Versus Vedolizumab In The Management Of Immune Checkpoint Inhibitor-Induced Colitis: A Systematic Review And Meta-Analysis., Shreya Shambhavi, Harmanjeet Singh, Ganesh Ramaprasad, Murod Khikmatov, Varun Vankeshwaram, Kumar Ashish, Carlos Valladares, Tanushree Bhatt, Seth D Cohen

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Immune checkpoint inhibitors (ICIs) can cause severe gastrointestinal immune-related adverse events (irAEs), often leading to treatment interruption and increased morbidity. Immune-mediated colitis (IMC) ranges from mild diarrhea to life-threatening colitis, sometimes requiring urgent intervention. While corticosteroids are the first-line treatment, selective immunosuppressive therapy (SIT) with either infliximab or vedolizumab is used for steroid-refractory or dependent cases. However, standardized practices are lacking, and treatment decisions are largely left to provider discretion. This study compares infliximab and vedolizumab for IMC, focusing on remission rates, recurrence, SIT dosing, and systemic steroid exposure duration.

METHODS: We identified six retrospective cohort studies that compared …

Genotype Distribution Of Human Papillomavirus Among Women With Cervical Cancer Stratified By Hiv Status In Tanzania, Alita Mrema, Mamsau Ngoma, Emmanuel L. Lugina, Atukuzwe Kahakwa, Chacha Josiah Mwita, Salama Iddy, Eulade Rugengamizi, Kandali Samwel, John Ngowi, Salum J. Lidenge, Charles Wood, Julius Mwaiselage

School of Medicine Faculty Publications

Background Cervical cancer (CC) is the leading cancer among women in Tanzania, especially among those between the ages of 15 and 44. The prevalence of high-risk Human papillomavirus (HR-HPV)-16/18 women in the general population at any given time is 3.3%. HR-HPVs 16 or 18 are the primary cause of CC. The distribution of HPV genotypes among women with CC according to HIV status is unknown in Tanzania. This study aimed to determine the HPV genotype distribution according to HIV status among women with CC in Tanzania. Methods This cross-sectional study was done at Ocean Road Cancer Institute (ORCI) in Tanzania …

Detection Of Activity Cliffs Produced By Anti-Cancer Drugs And An Algorithm For Reliable Predictions In Affected Areas, Sarah Josephine Aurit

Department of Statistics: Dissertations, Theses, and Student Research

An activity cliff (AC) occurs when drugs close in chemical space produce dissimilar biological results. We focus on developing an inferential procedure to detect the presence of ACs in a chemical landscape. If detected, we provide a distance-based procedure that can be used to identify regions of stability in the chemical landscape of interest and generate prediction with higher precision in those areas of stability. We conceptualize the chemical landscape as a spatial random field and use spatial models for prediction of efficacy for new drugs based on “distance” in chemical space. We argue that an AC manifests itself by …

Identifying And Breaking Barriers: Addressing Disparities In The Care Of Patients With Gynecologic Cancers, Bhavana Pothuri, Michele Muir, Jean Hurteau, John Farley, Michelle D. Lightfoot, Summer Dewdney, Tara Castellano, John K. Chan, Sharad Ghamande, Al Asante-Facey, Marina Stasenko, B J. Rimel, Electra D. Paskett

School of Medicine Faculty Publications

BACKGROUND: Significant disparities exist in the care of patients with gynecologic malignancies. Higher incidences of gynecologic malignancies among underrepresented subpopulations (eg, racial, ethnic, and/or LGBTQAI+) and lack of representative enrollment within clinical trials have highlighted the need to improve healthcare equity. We aimed to identify barriers to equitable health care and clinical trial participation for specific diverse populations of patients with gynecologic malignancies and to identify potential solutions for overcoming these barriers. METHODS: A series of 4 live and 3 asynchronous advisory boards facilitated by GSK was conducted between January 2023 and July 2024; live advisory boards were population specific. …

Evolution Of Esophageal Adenocarcinoma From Precursor Lesion Stem Cells, Wa Xian, Shan Wang, Jingzhong Xie, Yusuke Yamamoto, Melina Khorrami, Yanting Zhang, Raul Caballero Montes, Caycel Desales, Melika Khorrami, Zaal Mory, Ashley Hoffman, Amber Su, Crystal Nguyen, Peter J A Davies, Clifford Stephan, Shuang Pan, Wengen Wu, Yuxin Liu, Jeremy Siegelman, Rebecca E Waters, William A Ross, Shumei Song, Mark Metersky, David G Beer, Christopher P Crum, Alexander J Stewart, Matthew Vincent, Richard Russell, Robert A Izard, Khek Yu Ho, Jack Hung-Sen Lai, William W Bachovchin, Jaffer A Ajani, Frank D Mckeon

Faculty, Staff and Student Publications

Background & aims: Metastatic cancers arise from a decades-long succession of increasingly virulent precursor lesions, each of which represents prospective targets for therapeutic intervention. This evolutionary process has been particularly vivid in esophageal adenocarcinoma (EAC), as this cancer and associated precursor lesions, including Barrett's esophagus (BE), low-grade dysplasia (LGD), and high-grade dysplasia (HGD), coexist in an accessible, 2-dimensional pattern in esophageal mucosa. Given the durability of these precursor lesions, it is likely that they, like EAC, rely on stem cells for their regenerative growth. To assess the role of stem cells in the evolution of EAC, we apply technology that …

Effects Of Neoadjuvant Immunotherapy On Hearing In Patients With Head And Neck Squamous Cell Carcinoma, Bryce Hambach, Anhelina Bilokon, John Lee, L. Noelle Allemang, Jennifer Chisholm, Chris K. Zalewski, Julie Christensen, Carmen C. Brewer, James L. Gulley, Clint T. Allen, Lisa L. Cunningham, Katharine A. Fernandez

SKMC Student Presentations and Publications

Immune checkpoint blockade (ICB) is a commonly used treatment modality for cancer with a growing list of oncologic indications. Ototoxicity is a potential immune-related adverse event of ICB treatment, but the risk of hearing loss after ICB remains unknown. This retrospective chart review sought to identify individuals who received ICB and had available audiometric data before and after treatment in order to identify clinically meaningful changes in hearing. This single center, institutional chart review examined hearing function data in patients who underwent audiometry before and after ICB treatment. Measures included pure tone thresholds, distortion product otoacoustic emissions (DPOAEs), tympanometry, and …

Refinement Of Hyams Grading Criteria For Olfactory Neuroblastoma In An Endoscopic Sinus Surgery Predominant Cohort With Extended Follow-Up: Worth The Effort?, Stacey Gargano, Vincent Cracolici, Carl Snyderman, Eric Wang, Garret Choby, Aron Pollack, Paul Gardner, Diana Bell, Raja Seethala

Computational Medicine Center Faculty Papers

BACKGROUND: Hyams grading is considered prognostic in olfactory neuroblastoma (ONB), but grading criteria are subjective and predate modern classification and surgical approach. We evaluate the application of granular grading criteria to an endoscopic surgery predominant cohort with extended follow-up.

METHODS: 78 ONB patients were identified (1994-2019) with original diagnoses dating to 1979. Original Hyams grade, Modified Hyams grade incorporating more detailed criteria and other histologic features (i.e. divergent differentiation, clear cell/oncocytic change, and spindling) were assessed if feasible, evaluated for distribution by grade and correlated with outcomes.

RESULTS: Original Hyams grade (n = 43) distribution was: I: 4 (9%), II: …