Neoplasms Commons^™

Chemoradiation Treatment With Or Without Concurrent Tumor-Treating Fields (Ttfields) Therapy In Newly Diagnosed Glioblastoma (Gbm) Patients In China, Liping Liang, Lingchao Chen, Chunxia Ni, Wenyin Shi, Zhirui Zhou, Shu Chen, Wenjia Zhu, Jiabing Liu, Xianxin Qiu, Wanzun Lin, Junyan Zhang, Zhiyong Qin, Yang Wang

Department of Radiation Oncology Faculty Papers

BACKGROUND: Tumor-treating fields (TTFields) therapy and radiotherapy may have synergistic anti-glioma effect based on preclinical studies. The combination of chemoradiation therapy (CRT) with TTFields therapy has noticeably attracted clinicians' attention. This study aimed to provide insights into the clinical outcomes of patients with newly diagnosed glioblastoma who received either concurrent CRT and TTFields therapy or adjuvant TTFields therapy following CRT. The findings were based on a cohort of patients who were treated at Huashan Hospital (Shanghai, China).

METHODS: This retrospective study analyzed ndGBM patients' clinical outcomes who were treated at Huashan Hospital and received TTFields therapy. Patients were categorized into …

A Randomized Phase Ii/Iii Study Of Paclitaxel/Carboplatin/Metformin Versus Paclitaxel/Carboplatin/Placebo As Initial Therapy For Measurable Stage Iii Or Iva, Stage Ivb, Or Recurrent Endometrial Cancer: An Nrg Oncology/Gog Study, Victoria L. Bae-Jump, Michael W. Sill, Paola A. Gehrig, Jason D. Merker, David L. Corcoran, Adam D. Pfefferle, Michele C. Hayward, Joan L. Walker, Andrea R. Hagemann, Steven E. Waggoner, Roisin E. O'Cearbhaill, Megan E. Mcdonald, Mitchell I. Edelson, Paul A. Disilvestro, Amy L. Mcnally, Aimee Fleury, Ramey D. Littell, Frederick R. Ueland, Heather A. Lankes, Carol Aghajanian

Abington Jefferson Health Papers

INTRODUCTION: We evaluated the efficacy of the addition of the anti-diabetic drug metformin to standard-of-care paclitaxel and carboplatin (PC) in patients with advanced and recurrent endometrial cancer (EC).

METHODS: In this phase II/III trial, EC patients with chemotherapy-naïve stage III/IVA (with measurable disease) and stage IVB or recurrent (with or without measurable disease) disease were randomly assigned to PC/metformin (850 mg BID) versus PC/placebo. Metformin or placebo was continued as maintenance therapy after completion of PC until disease progression. The primary endpoint of phase II was progression-free survival (PFS). The primary endpoint of phase III was overall survival (OS). Secondary …

Superior Vena Cava Syndrome Due To Germ Cell Tumor In A Young Adult: Case Report, Manlio F. Lara Duck, Netzahualcoyotl Mayek Pérez, Juan Rosales Martínez

Research Symposium

Background: In superior vena cava syndrome (SVCS), the superior vena cava becomes mechanically obstructed by venous thrombus formation or by compression caused by intrathoracic tumors. SVCS is most common in men over 45 years of age; 22.5% of patients with SVCS have stage IV lung cancer or lymphoma. SVCS may occur secondary to extrathoracic tumors (testicular, ovarian, kidney, intestinal).

Case presentation: Male (24 years old) with a history of cancer in his maternal grandmother; denied drug addiction. Factory worker who denied being in direct contact with any chemicals and/or toxins. He reported non-productive cough; paroxysmal unilateral left facial edema without …

Alk Drives Neuroblastoma Tumorigenesis Via Upregulation Of Postn And Activation Of Wnt And Stat3 Signaling, Miller Huang, Wanqi Fang, Alvin Farrel, Linwei Li, Tania Porras Corredor, Shahab Asgharzadeh, John Maris, William A. Weiss

Research Symposium

Background: Neuroblastoma (NB) is the most common extracranial solid tumor in children. Two of the earliest known genetic drivers of NB are the oncogene MYCN and receptor tyrosine kinase ALK. While animal models show MYCN and mutationally active ALK F1174L can accelerate NB tumorigenesis, the mechanism of this cooperation is unknown. This study applied a human stem cell-based model to elucidate how ALK cooperates with MYCN to accelerate tumorigenesis of NB.

Methods: Induced pluripotent stem cells (iPSCs) were engineered with doxycycline-inducible MYCN and constitutively active ALKF1174L. These iPSCs were differentiated into trunk neural crest cells (tNCCs) and orthotopically transplanted into …

The Link Between Alcohol And Cancer: An Under Recognized Major Public Health Problem., Ihsan Salloum

Research Symposium

Objectives: Alcohol use related consequences is a worldwide major public health problem. Alcohol use is globally responsible for three million deaths each year and accounts for 5.1% of the global burden of disease. It accounts for the highest proportion of premature mortality among those ages between 15 and 49 years of age. Alcohol use has been linked to more than 200 disease and injury conditions and to poor health and disabilities of millions of people. While the link between alcohol and cancer has been recognized for a while, the awareness of such connection is still limited among the public …

Plasma Cell-Rich Lymphoid Neoplasm In An Endocervical Polyp Of The Uterine Cervix In A Perimenopausal 52-Year-Old Woman, Anjali Patel, Jacqueline Haas, Angela Kueck

HCA Healthcare Journal of Medicine

Background

The adaptive immune system consists of T and B lymphocytes, with some B lymphocytes further differentiating into plasma cells that secrete antibodies and make up the humoral immune system. Extramedullary plasmacytoma, mucosa-associated lymphoid tissue (MALT) lymphoma, and plasmablastic lymphoma are all plasma cell-rich lymphoid neoplasms that rarely present in the female genital tract. To date, few case reports of these malignancies arising within the uterine cervix exist.

Case Presentation

This case report describes a 52-year-old perimenopausal woman who presented to her primary obstetrician-gynecologist for an annual exam with the complaint of light spotting following an endometrial ablation that occurred …

Reduction Of Prostate Cancer Risk: Role Of Frequent Ejaculation-Associated Mechanisms., Mohamed Hassan, Thomas W. Flanagan, Abdulaziz M. Eshaq, Osama K. Altamimi, Hassan Altalag, Mohamed Alsharif, Nouf Alshammari, Tamadhir Alkhalidi, Abdelhadi Boulifa, Siraj M. El Jamal, Youssef Haikel, Mossad Megahed

School of Medicine Faculty Publications

Simple Summary: There is considerable evidence to suggest that frequent ejaculation reduces the risk of prostate cancer. The more frequently ejaculation occurs without risky sexual behavior, the lower the risk of prostate cancer. The mechanisms regulating the reduction in PCa risk associated with frequent ejaculations are attributed to the suppression of the sympathetic nervous system, resulting in a relief of tension and a slowing of the division of prostate epithelial cells. It is suggested that ejaculation frequency affects gene expression in prostate tissue and subsequently influences the susceptibility of the tissue to tumor formation, leading to a reduction in the …

The Association Of Physical Activity With Survival In Colon Cancer Versus A Matched General Population: Data From Cancer And Leukemia Group B 89803 And 80702 (Alliance)., Justin C. Brown, Chao Ma, Qian Shi, Leonard B. Saltz, Anthony F. Shields, Jeffrey A. Meyerhardt

School of Medicine Faculty Publications

Background: Colon cancer patients have inferior overall survival than a matched general population (MGP). It is unknown if physical activity is associated with a reduction in this survival disparity. Methods: Data were analyzed from two National Cancer Institute–sponsored postoperative treatment trials in stage III colon cancer, Cancer and Leukemia Group B (CALGB) 89803 and 80702, with 2876 patients who self-reported physical activity. Physical activity was converted to metabolic equivalents (MET-hours/week). The MGP was derived from the National Center for Health Statistics and matched on age, sex, and year. Results: In CALGB 89803, among patients who were alive at 3 years, …

Summary From The Nci Clinical Trials Planning Meeting On Next Generation Of Clinical Trials In Non-Muscle Invasive Bladder Cancer, Andrea Apolo, Brian C. Baumann, Hikmat Al-Ahmadie, Leslie Ballas, Rick Bangs, Kenneth Brothers, Stephanie Cooper Greenberg, Scott Delacroix, James J. Dignam, Jason A. Efstathiou, Adam S. Feldman, Jared C. Foster, Noah M. Hahn, Emma Hall, Donna E. Hansel, Jean Hoffman-Censits, Ashish M. Kamat, Sophia C. Kamran, Francesca Khani, Seth P. Lerner, Robert Lipman, Bhupinder Mann, David Mcconkey, James Mckiernan, Tracy L. Rose, Angela B. Smith, Catherine Tangen, Abdul Tawab Amiri, Chana Weinstock, Et Al

School of Medicine Faculty Publications

The National Cancer Institute organized a virtual Clinical Trials Planning Meeting (CTPM) on 'Defining the next generation of clinical trials with combination therapies in non-muscle invasive bladder cancer (NMIBC)' led by the Bladder Cancer Task Force of the NCI Genitourinary Cancers Steering Committee. The purpose of this meeting was to accelerate advances in clinical trials for patients with high-risk NMIBC. The meeting delivered a multidisciplinary expert consensus on optimal strategies for next-generation clinical trial designs in NMIBC with prioritization of combination therapies. Two clinical trial concepts were developed for potential implementation within the National Clinical Trials Network.

Bilateral Carotid Body Paragangliomas With Succinate Dehydrogenase Complex Subunit D Gene Mutation, Abdul R. Khan, Kelvin Li, Neel D. Gupta, Jagan D. Gupta, Mohammed M. Ansari, Triet M. Do, Enrique Palacios

School of Medicine Faculty Publications

No abstract provided.

Time To Initiation Of Antiresorptive Agents In Multiple Myeloma To Reduce Skeletal Related Events, Amman Bhasin, Adam Binder, Leland Damron, Amry Majeed, Adam Barsouk, Kelly Hughes, Thomas Jefferson University, Abdullateef O. Abdulkareem, Tingting Zhan, Divya Polu, Sai Gundepalli, Srinivas Devarakonda

Kimmel Cancer Center Faculty Papers

Purpose: Current treatment guidelines strongly support the use of antiresorptive therapy in patients with newly diagnosed multiple myeloma (NDMM) with the goal of preventing skeletal related events (SRE). Despite these concrete, data-driven recommendations, the impact of delays in antiresorptive initiation in NDMM patients is understudied. Through a multicenter retrospective study, we examined the impact of delays in antiresorptive initiation on the rates of SREs. We furthered our exploration of this topic in a separate retrospective analysis with a focus on reasons for delays in antiresorptive therapy initiation. Methods: Electronic health records from two large academic institutions were used to identify …

Mir-125a-3p And Its Targets: Promising Biomarkers For Ovarian, Liver, And Breast Cancers, Offering A Beacon Of Hope For More Effective Diagnosis And Treatment Strategies, Eman Kamaleldien Anwer

Theses and Dissertations

Cancer is a worldwide health problem with various genetic and epigenetic alterations, resulting in disease heterogeneity. Effective diagnostic, therapeutic, and monitoring markers have been determined recently; however, new diagnostic, prognostic, and therapeutic markers are needed. MicroRNAs (miRNA), short non-coding RNAs, have a highlighted role in cancer progression, migration, and programmed cell death. Our study aims to investigate the significance of miR-125a-3p and its downstream targets in breast (BRCA), hepatocellular (HCC), and ovarian (OVCA) malignancies and their possibility as diagnostic biomarkers and targets for therapeutic agents. Bioinformatics and online tools were used to determine the miRNA-predicted downstream targets, analyze GEO datasets, …

The First International Experience With Histotripsy: A Safety Analysis Of 230 Cases, Chase J. Wehrle, Kevin Burns, Evan Ong, Allison Couillard, Neehar D. Parikh, Elaine Caoili, Jaekeun Kim, Federico Aucejo, Andrea Schlegel, Emily Knott, Paul Laeseke, J Philip Boudreaux, Philipp Von Breitenbuch, Mikhail Silk, Mohamed Alassas, Andrew Guzowski, Brian Fuller, Erica Knavel Koepsel, Brock Hewitt, Mishal Mendiratta-Lala, David C. Kwon

School of Medicine Faculty Publications

BACKGROUND: Histotripsy is a novel, noninvasive, nonionizing, and nonthermal approach that uses focused ultrasound waves to treat liver tumors. This technology received a de novo Food and Drug Administration grant in late 2023. This study aimed to provide the first report on post-trial real-world clinical safety data. METHODS: Safety outcomes within 30 days of histotripsy were collected after obtaining Food and Drug Administration clearance (December 22, 2023 to July 26, 2024). All centers that performed histotripsy were invited to participate in this study. Complications requiring treatment were graded using the Clavien-Dindo classification and Comprehensive Complication Index (CCI). RESULTS: A total …

Self Supervised Artificial Intelligence Predicts Poor Outcome From Primary Cutaneous Squamous Cell Carcinoma At Diagnosis, Nicolas Coudray, Michelle C. Juarez, Maressa C. Criscito, Adalberto Claudio Quiros, Reason Wilken, Stephanie R. Jackson Cullison, Mary L. Stevenson, Nicole A. Doudican, Ke Yuan, Jamie D. Aquino, Daniel M. Klufas, Jeffrey P. North, Siegrid S. Yu, Fadi Murad, Emily Ruiz, Chrysalyne D. Schmults, Cristian D. Cardona Machado, Javier Cañueto, Anirudh Choudhary, Alysia N. Hughes, Alyssa Stockard, Zachary Leibovit-Reiben, Aaron R. Mangold, Aristotelis Tsirigos, John A. Carucci

Department of Dermatology and Cutaneous Biology Faculty Papers

Primary cutaneous squamous cell carcinoma (cSCC) is responsible for ~10,000 deaths annually in the United States. Stratification of risk of poor outcome at initial biopsy would significantly impact clinical decision-making during the initial post operative period where intervention has been shown to be most effective. Using whole-slide images (WSI) from 163 patients from 3 institutions, we developed a self supervised deep-learning model to predict poor outcomes in cSCC patients from histopathological features at initial diagnosis, and validated it using WSI from 563 patients, collected from two other academic institutions. For disease-free survival prediction, the model attained a concordance index of …

Single-Cell Rna Sequencing Identifies Molecular Biomarkers Predicting Late Progression To Cdk4/6 Inhibition In Patients With Hr+/Her2- Metastatic Breast Cancer, Linjie Luo, Peng Yang, Sofia Mastoraki, Xiayu Rao, Yan Wang, Nicole M Kettner, Akshara Singareeka Raghavendra, Debasish Tripathy, Senthil Damodaran, Kelly K Hunt, Jing Wang, Ziyi Li, Khandan Keyomarsi

Faculty, Staff and Student Publications

Background: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) in combination with endocrine therapy are the standard treatment for patients with hormone receptor-positive, HER2-negative metastatic breast cancer (mBC). Despite the efficacy of CDK4/6is, intrinsic resistance occurs in approximately one-third of patients, highlighting the need for reliable predictive biomarkers.

Methods: Single-cell RNA sequencing analyzed metastatic tumors from HR+/HER2- mBC patients pre-CDK4/6i treatment at baseline (BL) and/or at disease progression. BL samples were from CDK4/6i responders (median progression-free survival [mPFS] = 25.5 months), while progressors were categorized as early-progressors (EP, mPFS = 3 months) and late-progressors (LP, mPFS = 11 months). Metastatic sites included liver, …

An Open-Label Study To Determine The Maximum Tolerated Dose Of Oral Esk-440 Administered As A Single Agent In Patients With Advanced Or Metastatic Solid Tumors, Russell J. Schilder, Drew Rasco, Manish R. Sharma

Kimmel Cancer Center Faculty Papers

PURPOSE: Anaplastic lymphoma kinase (ALK) dysregulation is implicated in numerous cancers. Tyrosine kinase inhibitors (TKIs) targeting ALK have improved disease outcomes, but resistance mechanisms are common. This first-in-human trial evaluates ESK-440, a dual inhibitor of ALK and focal adhesion kinase, as a novel strategy for cancers with resistance to ALK-targeting TKIs.

METHODS: This phase 1, open-label, dose-finding study evaluated the maximum tolerated dose (MTD), safety, efficacy, and pharmacokinetics of ESK-440 in participants with advanced or metastatic solid tumors (ClinicalTrials.gov: NCT01922752). A 3 + 3 dose-escalation design, with daily doses ranging from 25 to 700 mg/day of ESK-440 for each 28-day …

Durable Responses To Immune Checkpoint Inhibitor-Based Regimens For Metastatic Clear Cell Renal Cell Carcinoma Stratified By Imdc Risk Groups: A Pooled Analysis Of Four Randomized Phase 3 Trials, Albert Jang, Jeffrey Y. Zhong, Hamsa L.S. Kumar, Kevin K. Zarrabi, Alec Zhu, Abby L. Grier, Adam Calaway, Jonathan E. Shoag, Laura Bukavina, Angela Y. Jia, Prateek Mendiratta, Iris Y. Sheng, Santosh Rao, Jason R. Brown, Jorge A. Garcia, Seunghee Margevicius, Pingfu Fu, Pedro C. Barata

Department of Medical Oncology Faculty Papers

Background: An immune checkpoint inhibitor (ICI) backbone is a standard of care for frontline metastatic clear cell renal cell carcinoma, involving either ICI doublet or tyrosine kinase inhibitor (TKI) with ICI. These phase 3 trials used a sunitinib control arm. The optimal regimen is uncertain. Objective: To compare long-term responders of these trials using extended follow-up data stratified by International Metastatic RCC Database Consortium risk group. Methods: Phase 3 trial data (CheckMate 214, KEYNOTE-426, CheckMate 9ER, and CLEAR) with a minimum follow-up of four years was used. Pseudo individual patient data (IPD) was obtained from Kaplan-Meier curves using the graph …

Celebrating World Cancer Day: Innovative Biological Approaches To Cancer And Their Alignment With Sustainable Development Goals (Sdgs), Hamed Kioumarsi, Bolin Liu

School of Medicine Faculty Publications

No abstract provided.

Exploring Access To Care In Zimbabwe Using The 3-Delay Model, Katerina Green, Naboth Matinhira, Amiti Jain, Tissiana Vallecillo, Priya Arya, Estephania Candelo, Munyaradzi Katiro, Tafadzwa Nyamurowa, Dontre' Douse, Joshua Wiedermann

SKMC Student Presentations and Publications

OBJECTIVES: We aim to identify the diversity of barriers to care for otolaryngology-head and neck surgery patients in Harare, Zimbabwe.

METHODS: Interviews were conducted at four general otolaryngology clinics in Harare in October 2022.The patient population included children and adults presenting to either government or private clinics. Via interpreter, six standardized questions were discussed with each patient. Survey responses were used to categorize patients into one or more of three types of delays: (1) deciding to seek care, (2) reaching the appropriate healthcare facility, and (3) receiving adequate care after reaching that facility.

RESULTS: Forty-six patients participated in this survey. …

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

Kimmel Cancer Center Faculty Papers

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 …

Analyzing The Creation And Use Of Abbreviations In Cardiology And Cardiac Imaging Society Guidelines, Christopher R Green, Rui Zhang, Raymond F Stainback, Sofia W Ye, Daniel E Forsha, Enrique Garcia-Sayan, Jeffrey C Hill, Carol Mitchell, Vera H Rigolin, Vandana Sachdev, Partho P Sengupta, Vincent L Sorrell, Jordan B Strom, Alexander M Ye, Cynthia C Taub

Faculty, Staff and Students Publications

BACKGROUND: Abbreviation use in clinical and academic cardiology is widespread, yet there are few guidelines regulating the creation and utilization of abbreviations. Inconsistent abbreviations can introduce ambiguity and pose challenges to practice and research.

OBJECTIVES: The authors aimed to analyze how abbreviations are created and utilized in general cardiology and cardiac imaging society guidelines in order to assess whether ambiguities and discrepancies exist between societies.

METHODS: Abbreviation data were collected from 7 national and international societies of general cardiology and cardiac imaging over a 6-year span (2018-2023). Data were linguistically coded for abbreviation type, unique occurrence, meaning or sense count, …

Atypical Presentation Of Non-Small Cell Lung Carcinoma With Metastasis To Breast Tissue, Tylar P. Seckman, Diane Krutzler-Berry, Mohamed Ashal, Waqas Mahmud, Krista L. Denning, Logan M. Lawrence

Marshall Journal of Medicine

Malignant neoplasms of the lung commonly metastasize to lymph nodes, bone, brain, and liver via hematogenous and lymphatic routes. Much less commonly, metastasis occurs in the breast. Secondary metastatic disease of the breast is very rare, with a reported incidence ranging from 0.4-1.3%­­—with primary lung cancer being one of the most anomalous sources. This case details non-small cell lung cancer metastasis to the breast with proven primary contralateral lung origination. This atypical finding prompts medical professionals to consider these malignant cells' immunologic, histologic, and pathologic makeup to understand further and treat the neoplasm.

Genetic Ancestry Concordant Rna Splicing In Prostate Cancer Involves Oncogenic Genes And Associates With Recurrence, Muthana Al Abo, Wen-Chi Foo, Lauren Howard, Shannon Mcgue, Bonnie Lacroix, Julie Kephart, Angela Clayton, Blair Thornburg, Monika Anand, Michael Rothberg, Shannon Mccall, Jiaoti Huang, Thomas Esther, Judd Moul, Michael Ferrandino, Thomas Polascik, Cary Robertson, Brant Inman, Andrew Armstrong, Yuan Wu, Terry Hyslop, Daniel George, Steven Patierno, Jennifer Freedman

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Black men suffer disproportionately from prostate cancer (PCa) compared to men of other races and ethnicities. Comparing the molecular landscape of PCa among Black and White patients has the potential to identify targets for development of new precision medicine interventions. Herein, we conducted transcriptomic analysis of prostate tumors and paired tumor-adjacent normals from self-reported Black and White PCa patients and estimated patient genetic ancestry. Clinical follow-up revealed increased biochemical recurrence (BCR) among Black patients compared to White patients with high-grade PCa. Transcriptomic analysis identified differential alternative RNA splicing events (ARSs) between Black and White PCa patients. Genes undergoing genetic ancestry-concordant …

Il-1Β In Neoplastic Disease And The Role Of Its Tumor-Derived Form In The Progression And Treatment Of Metastatic Prostate Cancer, Yetunde Oyende, Luke Taus, Alessandro Fatatis

Kimmel Cancer Center Faculty Papers

Since its discovery, IL-1β has taken center stage as a key mediator of a very broad spectrum of diseases revolving around immuno-mediated and inflammatory events. Predictably, the pleiotropic nature of this cytokine in human pathology has led to the development of targeted therapeutics with multiple treatment indications in the clinic. Following the accumulated findings of IL-1β's central modulatory role in the immune system and the implication of inflammatory pathways in cancer, the use of IL-1β antagonists was first proposed and then also pursued for oncology disorders. However, this approach has consistently relied on the perceived need of interfering with IL-1β …

Discontiguous Recurrences Of Idh-Wildtype Glioblastoma Share A Common Origin With The Initial Tumor And Are Frequently Hypermutated, Malcolm F Mcdonald, Sricharan Gopakumar, Tareq A Juratli, Ilker Y Eyüpoglu, Ganesh Rao, Jacob J Mandel, Ali Jalali

Faculty, Staff and Students Publications

Glioblastoma is the deadliest primary brain tumor, largely due to inevitable recurrence of the disease after treatment. While most recurrences are local, patients rarely present with a new discontiguous focus of glioblastoma. Little is currently known about the genetic profile of discontiguous recurrences. In our institutional database, we identified 22 patients with targeted exome sequencing of pairs of initial and recurrent IDH-wildtype glioblastoma. Recurrences were classified as contiguous or discontiguous based on the presence or absence of T2 FLAIR signal connection to the initial site of disease on MRI. Exome analysis revealed shared driver and passenger mutations between discontiguous recurrences …

The C-Terminal Phdvc5hch Tandem Domain Of Nsd2 Is A Combinatorial Reader Of Modified H3k4 And Tri-Methylated H3k27 That Regulates Transcription Of Cell Adhesion Genes In Multiple Myeloma, Andrea Berardi, Charlotte Leonie Kaestner, Michela Ghitti, Giacomo Quilici, Paolo Cocomazzi, Jianping Li, Federico Ballabio, Chiara Zucchelli, Stefan Knapp, Jonathan Licht, Giovanna Musco

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Histone methyltransferase NSD2 (MMSET) overexpression in multiple myeloma (MM) patients plays an important role in the development of this disease subtype. Through the expansion of transcriptional activating H3K36me2 and the suppression of repressive H3K27me3 marks, NSD2 activates an aberrant set of genes that contribute to myeloma growth, adhesive and invasive activities. NSD2 transcriptional activity also depends on its non-catalytic domains, which facilitate its recruitment to chromatin through histone binding. In this study, using NMR, ITC and molecular dynamics simulations, we show that the tandem PHD domain of NSD2 (PHDVC5HCHNSD2) is a combinatorial reader of unmodified histone H3K4 and tri-methylated H3K27 …

Genetics And Biology Of Pancreatic Ductal Adenocarcinoma, Haoqiang Ying, Alec C Kimmelman, Nabeel Bardeesy, Raghu Kalluri, Anirban Maitra, Ronald A Depinho

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) poses a grim prognosis for patients. Recent multidisciplinary research efforts have provided critical insights into its genetics and tumor biology, creating the foundation for rational development of targeted and immune therapies. Here, we review the PDAC genomic landscape and the role of specific oncogenic events in tumor initiation and progression, as well as their contributions to shaping its tumor biology. We further summarize and synthesize breakthroughs in single-cell and metabolic profiling technologies that have illuminated the complex cellular composition and heterotypic interactions of the PDAC tumor microenvironment, with an emphasis on metabolic cross-talk across cancer and …

Targeted Inhibition Of Aurora Kinase A Promotes Immune Checkpoint Inhibition Efficacy In Human Papillomavirus-Driven Cancers, Soma Ghosh, Madison P O'Hara, Pragya Sinha, Tuhina Mazumdar, Lacin Yapindi, Jagannadha K Sastry, Faye M Johnson

Faculty, Staff and Student Publications

Background: Human papillomavirus (HPV)-driven cancers include head and neck squamous cell carcinoma and cervical cancer and represent approximately 5% of all cancer cases worldwide. Standard-of-care chemotherapy, radiotherapy, and immune checkpoint inhibitors (ICIs) are associated with adverse effects and limited responses in patients with HPV-driven cancers. The integration of targeted therapies with ICIs may improve outcomes. In a previous study, we demonstrated that Aurora kinase A (AURKA, Aurora A) inhibitors lead to apoptosis of human HPV-positive cancer cells in vitro and in vivo. Here, we explored the potential of Aurora A inhibition to enhance response to ICIs in immune-competent …

Multiparametric Mri Along With Machine Learning Predicts Prognosis And Treatment Response In Pediatric Low-Grade Glioma, Anahita Fathi Kazerooni, Adam Kraya, Komal Rathi, Meen Chul Kim, Arastoo Vossough, Nastaran Khalili, Ariana Familiar, Deep Gandhi, Neda Khalili, Varun Kesherwani, Debanjan Haldar, Hannah Anderson, Run Jin, Aria Mahtabfar, Sina Bagheri, Yiran Guo, Qi Li, Xiaoyan Huang, Yuankun Zhu, Alex Sickler, Matthew R Lueder, Saksham Phul, Mateusz Koptyra, Phillip Storm, Jeffrey Ware, Yuanquan Song, Christos Davatzikos, Jessica Foster, Sabine Mueller, Michael J Fisher, Adam Resnick, Ali Nabavizadeh

Department of Neurosurgery Faculty Papers

Pediatric low-grade gliomas (pLGGs) exhibit heterogeneous prognoses and variable responses to treatment, leading to tumor progression and adverse outcomes in cases where complete resection is unachievable. Early prediction of treatment responsiveness and suitability for immunotherapy has the potential to improve clinical management and outcomes. Here, we present a radiogenomic analysis of pLGGs, integrating MRI and RNA sequencing data. We identify three immunologically distinct clusters, with one group characterized by increased immune activity and poorer prognosis, indicating potential benefit from immunotherapies. We develop a radiomic signature that predicts these immune profiles with over 80% accuracy. Furthermore, our clinicoradiomic model predicts progression-free …

Co-Occurrence Of Autoimmune Hepatitis And Pheochromocytoma: A Complex Diagnostic And Treatment Challenge, Himani Patel, Gabrielle Aiello, Taylor Frazier, Sage Havrilla, Payton Williams, Meghan Rosenquist

South Atlantic Division GME Research Day 2025

No abstract provided.