Neoplasms Commons^™

Malt1 Protease Inhibition Restrains Glioblastoma Progression By Reversing Tumor-Associated Macrophage-Dependent Immunosuppression In Mice, Juliana Hofstätter Azambuja, Saigopalakrishna Yerneni, Lisa Maurer, Hannah Crentsil, Gabriela Debom, Linda Klei, Mei Smyers, Chaim Sneiderman, Kristina Schwab, Rajesh Acharya, Aivi Nguyen, Josie Emery, John Little, Jeffrey Meridew, Yijen Lin Wu, Prasanna Ekambaram, Dong Hu, Pete Gough, John Bertin, Ari Melnick, Gary Kohanbash, Riyue Bao, Peter Lucas, Linda Mcallister-Lucas

College of Life Sciences Faculty Papers

MALT1 protease is an intracellular signaling molecule that promotes tumor progression via cancer cell-intrinsic and cancer cell-extrinsic mechanisms. MALT1 has been mostly studied in lymphocytes, and little is known about its role in tumor-associated macrophages. We show that MALT1 is expressed in glioblastoma (GBM)-associated macrophages. Mechanistically, GBM tumor cells induce a MALT1-NF-κB signaling axis in macrophages, leading to enhanced macrophage migration and polarization toward an immunosuppressive ('M2-like') phenotype. Inactivation of MALT1 protease promotes transcriptional reprogramming that reduces migration and restores a macrophage anti-tumor 'M1-like' phenotype. Preclinical in vivo analysis shows that MALT1 inhibitor treatment results in immuno-reactivity of GBM-associated macrophages …

Metastatic Large Cell Neuroendocrine Carcinoma: A Rare Cause Of Hypopituitarism, Smriti Nair, Taskeen Ahmed, Jessica Watari

Division of Internal Medicine Faculty Papers & Presentations

Pituitary metastases from pulmonary large cell neuroendocrine carcinoma (LCNEC) are exceedingly rare but should be considered in patients presenting with arginine vasopressin deficiency and panhypopituitarism in the context of known or suspected metastatic lung cancer. Early recognition and prompt initiation of hormonal replacement therapy are essential to prevent life-threatening endocrine crises and to improve symptom burden. We describe a case of a 43-year-old male who presented with dyspnea, weight loss, and weakness who was found to have metastatic LCNEC involving the liver. Endocrine evaluation revealed central hypothyroidism, central adrenal insufficiency, and later arginine vasopressin deficiency manifested by polyuria and hypernatremia. …

Locoregional Therapy Pressure-Enabled Drug Delivery For Liver Cancers, Thomas Eggleston, Bassem Fayek, Jacqueline Kowalke, Mina Makary

Student Papers, Posters & Projects

Hepatic malignancies account for a substantial portion of global cancer mortality, with hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (IHC), and metastatic liver disease representing the most common diagnoses. While surgical resection and liver transplantation remain curative options for eligible patients, most patients are diagnosed at stages unsuitable for surgery. This has shifted medical management towards locoregional therapies (LRTs) which are often catheter-directed. Of these interventions, the use of conventional end-hole catheters for therapeutic infusion has been a mainstay of treatment, but this method is constrained by retrograde particle escape and elevated tumoral interstitial fluid pressure. Together, these factors limit drug penetration …

Cervical Cancer Screening Coverage And Associated Factors Among Women Aged 25-59 In Eswatini: Insights From The 2021 Population-Based Hiv Impact Assessment (Phia), Abenezer Melaku Tafese, Bikiltu Dirbaba, Meseker Fentie, Charnita Zeigler-Johnson

College of Population Health Faculty Papers

BACKGROUND: Cervical cancer is the most common cancer and the leading cause of cancer mortality among women in Eswatini, which reported the highest cervical cancer incidence and mortality rates globally in 2022. However, recent nationally representative published data on cervical cancer screening coverage in Eswatini remain limited. This study aimed to estimate cervical cancer screening coverage and identify factors associated with screening uptake among women aged 25-59 years in Eswatini.

METHOD: Data were drawn from the 2021 Eswatini Population-based HIV Impact Assessment (PHIA), a nationally representative cross-sectional household survey. Survey-weighted bivariable and multivariable logistic regression analyses were conducted to identify …

Feasibility And Acceptability Of Automated Texts To Offer, Screen, And Enroll Patients In A Cancer Clinical Trial Financial Reimbursement Program: Mixed Methods Study, Ashley E Santaniello, Hena Patel, Sarah Milinski, Mohan Balachandran, Vivian Nguyen, E. Paul Wileyto, Robert H. Vonderheide, Dana Dornsife, Robert G. Johnson, Carmen E. Guerra

Student Papers, Posters & Projects

BACKGROUND: Out-of-pocket (OOP) costs pose a significant barrier to participating in cancer clinical trials (CCTs). Financial reimbursement programs (FRPs) that reduce the burden of OOP costs can support participation in CCTs if the information is readily available to participants at the time of enrollment. Prior studies have shown the importance and impact of FRPs, but despite improvements, significant barriers still remain.

OBJECTIVE: This study was designed to explore the feasibility and acceptability of automated texts designed to offer, screen, and enroll CCT participants in an FRP for OOP travel and lodging-related clinical trial costs.

METHODS: This study used a mixed …

Meeting Report From The 2025 Cure Ocular Melanoma (Cure Om) Global Science Meeting, Amsterdam, The Netherlands, October 2025, Andrew E. Aplin, Katherina Alsina, Allison S. Betof, Joseph Birkett, Marcus O. Butler, George Cole, Rizwan Haq, Florian A. Karreth, Vinit B. Mahajan, Rahul Marpadga, Prithvi Mruthyunjaya, Paul Nathan, Jonas A. Nilsson, Gary Palmer, Joseph J. Sacco, Takami Sato, Sarah Stanhope, Pang-Ning Teng, Kyleigh Lipira

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

The 2025 Cure Ocular Melanoma (CURE OM) Global Science Meeting took place in Amsterdam, The Netherlands on October 25th, 2025. Several promising drug candidates are in development; however, there is still an urgent need for better prevention, detection, and treatment of uveal melanoma. The purpose of this meeting was to promote international collaboration and idea exchange between scientists, industry, and patient advocates.

Virtual Patient-Specific 3-Dimensional Specimen Maps For Adjuvant Radiation Therapy Planning In Mucosal Head And Neck Squamous Cell Carcinoma, Whitney Jin, Michael C. Topf, Marina Aweeda, Kavita Prasad, Olivia Prosak, Sindhura Sridhar, Zachary Kohutek, Sean All, D. W. Nathan Kim, Anthony Cmelak, Ryan Whitaker, Alexander Langerman, Kyle Mannion, Melanie Hicks, Sarah Rohde, Robert Sinard, Eben Rosenthal, Natalie A. Lockney

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

PURPOSE: Adjuvant radiation therapy planning for mucosal head and neck squamous cell carcinoma is challenging due to postoperative anatomic changes, contributing to variability in clinical target volume (CTV) delineation and risk of geographic miss or unnecessary dose expansion. Patient-specific 3-dimensional (3D) specimen maps may offer a novel approach to improve the localization of high-risk margins and facilitate multidisciplinary communication.

METHODS AND MATERIALS: In this prospective, noninterventional feasibility study, 3D scanning and virtual pathologic mapping of surgical specimens were performed as part of routine pathologic processing. Annotated 3D maps were integrated into the radiation therapy planning workflow and reviewed by the …

The Use Of Large Language Models In Enhancing Patient Education Materials For Pancreatic Neuroendocrine Tumors, Brendan Dolan, Aniela Crayton, Emerson Woodbury, Miguel Tzita, Eliza Beal Md, Gregory Dyson Phd

Medical Student Research Symposium

Background:

Incidence and prevalence of Pancreatic Neuroendocrine Tumors (PNETs) has increased in recent years. More than half of American adults endorse utilizing the internet within the past year to search for medical information. This study aims to investigate the use of Large Language Models (LLMs), a popular type of artificial intelligence, to improve the efficacy of online patient education materials (oPEMs) in providing accurate and digestible information to patients with a PNET diagnosis.

Methods: Content from 36 web pages related to PNET was transferred to two popular LLMs, Chat GPT and Google Gemini, with the prompt “rewrite the following text …

Defining A Multi-Omic, Ai-Enabled Stool Screening Paradigm For Colorectal Cancer: A Consensus Framework For Clinical Translation, Arturo Loaiza-Bonilla, Yan Leyfman, Viviana Cortiana, Rhys Crawford, Shivani Modi

Einstein Health Papers

Colorectal cancer (CRC) develops through both conventional adenoma-carcinoma and serrated neoplasia pathways, yet noninvasive screening still under-detects the advanced precursor lesions that enable true cancer prevention. Stool-based screening reduces CRC mortality, but its preventive impact remains constrained by limited detection of advanced precancerous lesions (APLs), including advanced adenomas and sessile serrated lesions. Next-generation multitarget stool DNA assays (mt-sDNA; e.g., Cologuard Plus) have established high sensitivity for CRC and specificity approaching 94%, leaving improved APL detection as the principal opportunity for innovation. This review presents a consensus framework for a multi-omic stool screening paradigm that integrates host epigenetic markers (DNA methylation) …

Nursing Practice In Cancer Treatment Decision Making Among Older Adults: A Scoping Review On Behalf Of The International Society Of Geriatric Oncology Nursing, Allied Health, And Scientists Interest Group, Fay J. Strohschein, Hanneke Van Der Wal-Huisman, K. Alix Hayden, Kristen R. Haase, Michelle Hannan, Cindy Kenis, Juan Li, Nikita Nikita, Sophie Pilleron, Tracy Ruegg, Heike Schmidt, Anke Steckelberg, Cassandra Vonnes, Martine Puts

Department of Medical Oncology Faculty Papers

INTRODUCTION: Cancer treatment decision making (CTDM) presents important challenges among older adults due to variation in health and functional status, presence of comorbidities, differing goals/values, quality and quantity of life considerations, and limited inclusion in clinical trials. Nursing standards and guidelines call for competence in supporting CTDM and nurses advocate for greater involvement. However, clear understanding of the existing evidence to inform nursing practice is lacking. We aimed to map and synthesize evidence that provides insight into nursing practice in CTDM among older adults, with attention to nursing roles, required skills and competencies, potential barriers and facilitators, and outcomes studied. …

Metabolic Responses To Freund’S Adjuvants And Oncolytic Viruses: Implications On Vaccines And Tumor Immunity, Kiruthiga Mone

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

Freund’s adjuvants have been extensively used in experimental research, and they modulate immune responses through various mechanisms. While both complete Freund’s adjuvant (CFA) and incomplete Freund’s adjuvant (IFA) contain the same mineral oil base, CFA contains the killed extract of Mycobacterium tuberculosis (M. tb) as an additional ingredient. Because the CFA contains mycobacterial content similar to that of Bacillus Calmette-Guérin (BCG), which induces trained immunity (TI), we tested the hypothesis that CFA may elicit TI-like features. To test this hypothesis, we investigated the metabolic and epigenetic reprogramming induced by CFA, with IFA and BCG as controls, in inbred …

Outcomes Of Radiation Integrated With T-Cell-Engaging Bispecific Antibodies In Relapsed/Refractory Multiple Myeloma, Heta Patel, Harper Hubbeling, Kyle Yu, Maribel Carpenter, Michael Lariviere, John Plastaras, Adam Cohen, Shivani Kapur, Dan Vogl, Adam Waxman, Edward Stadtmauer, Alfred Garfall, Sandra Susanibar-Adaniya

Student Papers, Posters & Projects

No abstract provided.

Management Of Acute Myeloid Leukemia: A Review, Chetan Jeurkar, Lana King, David Baek, Lindsay Wilde, Gina Keiffer, Margaret Kasner

Kimmel Cancer Center Faculty Papers

Background/Objectives: Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy with historically poor outcomes, particularly among older adults and patients harboring high-risk molecular features. Advances in genomic profiling have enabled the development of targeted therapies, reshaping treatment algorithms beyond conventional cytarabine-anthracycline induction and hypomethylating agent-based regimens. This review summarizes current evidence and emerging therapeutic strategies across four evolving areas: menin inhibition, FLT3 inhibition, IDH inhibition and treatment approaches for TP53-mutated AML. Methods: We reviewed published clinical trials, preclinical studies, and ongoing clinical trials evaluating targeted therapies in AML. Emphasis was placed on agents with regulatory approval or substantial clinical development, …

Metastatic Castrate-Resistant Prostate Cancer To The Penis Resulting In Malignant Priapism And Urethral Obstruction, Courtney Stewart, Joon Yau Leong, William Kevin Kelly, Mihir Shah

Department of Urology Faculty Papers

A 76-year-old male with metastatic castrate-resistant prostate cancer was found to have metastatic disease to the urethra and penis on PSMA PET scan. This resulted in constant pain due to obstruction of blood flow through the corpora cavernosum resulting in priapism and urethral obstruction. The patient underwent a radical penectomy, partial urethrectomy and perineal urethrostomy creation. Final pathology confirmed metastatic prostatic adenocarcinoma. Although rare, prostate cancer can metastasize to the corpora spongiosum or cavernosa. Treatment options are limited, and surgical excision with urinary diversion is likely to provide the most durable outcomes for one's quality of life.

Phytic Acid (Insp6) Activates Hdac3 Epigenetic Axis To Maintain Intestinal Barrier Function, Sujan Chatterjee, Zachery Sin, Nguyen Tran, Loretta Vierra, Anuj Shukla, Tam Tran, George Koshkaryan, Kevin Ritter, Xue Bessie Sue, Saharat Jolak Ragsac, Seungman Park, Qian Liu, Richard Van, Katherine Huang, Kayci Huff-Hardy, Richard Rood, Anas Gremida, Martin Gregory, Chien-Huan Chen, Mira V. Han, Parakkal Deepak, Adikfi Saiardi, Henning J. Jensen, Prasun Guha

Life Sciences Faculty Research

HDAC inhibition shows promise in cancer treatment but pan-HDAC inhibitors cause gastrointestinal issues in 48% of patients. Understanding HDAC activation mechanisms is crucial to treating diverse diseases beyond cancer. Our study reveals that inositol polyphosphate multikinase (IPMK) and inositol hexakisphosphate (InsP6 or phytic acid), enriched in vegan diets, play essential roles in activating the HDAC3 epigenetic axis and maintaining intestinal barrier integrity. IPMK binds to HDAC3 and drives InsP6 synthesis, which selectively activates HDAC3 at a 10 nM concentration by recruiting the DAD domain of its corepressor protein. IPMK deletion diminishes HDAC3 activation, leading to histone hyperacetylation and MMP gene …

Evaluation Of Large Language Models As Decision Support Tools For Head And Neck Cancer Management: A Blinded Multidisciplinary Simulation Study, Sholem Hack, Ron J. Karni, Antonino Maniaci, Christopher E. Fundakowski, Luca Castellani, Fabiola Incandela, Remo Accorona, Miguel Mayo-Yanez, Martina Violati, Lorenzo Giannini, Niccolo' Mevio, Alberto Maria Saibene

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

BACKGROUND: The management of head and neck cancer relies on multidisciplinary expertise; however, access to tumor boards remains variable. Large language models (LLMs) may support guideline-based decision-making, although performance in complex oncologic scenarios is not well defined.

METHODS: Fourteen synthetic cases based on real tumor board encounters were evaluated. Five blinded comparator arms produced recommendations: a human expert, Non-RAG-GPT-4, Non-RAG-GPT-5, RAG-GPT-4, and RAG-GPT-5. Eight head and neck oncologic surgeons scored each recommendation for appropriateness, clarity, specificity, and feasibility using 5-point Likert scales. Paired permutation testing and inter-rater reliability were assessed.

RESULTS: LLM outputs showed close alignment with expert recommendations. RAG-based …

Factors Associated With Upstaging In Patients With Resectable Non-Small Cell Lung Cancer: A Modern Institutional Sample, Sneha Alaparthi, Hamza Rshaidat, Luke Meredith, Scott H. Koeneman, Christina Grindley, Jacob Heilizer, Purab Kothari, Prarthna Chandar, Tyler Grenda, Nathaniel R. Evans Iii, Olugbenga T. Okusanya

Department of Surgery Faculty Papers

BACKGROUND: There is significant value in predicting and better assessing patients who are at risk of post-surgery upstaging in lung cancer. The objective of this study is to review patients who were upstaged following resection and evaluate their clinical and demographic data to elucidate which factors portend an increased risk of pathologic upstaging at our institution (the Thomas Jefferson University Hospital).

METHODS: A retrospective review of institutional data was performed between 2011 and 2023. Patients with stage I-II non-small cell lung cancer (NSCLC) were included. Patients were excluded if they received neoadjuvant systemic therapy, including chemotherapy and/or immunotherapy, and were …

Spatially Distinct Cellular And Molecular Landscapes Define Prognosis In Triple-Negative Breast Cancer, Kavitha Mukund, Darya Veraksa, David Frankhouser, Lixin Yang, Jerneja Tomsic, Raju Pillai, Srijan Atti, Zahra Mesrizadeh, Daniel Schmolze, Jovanny Zabaleta, Xiao-Cheng Wu, Mary-Anne Leblanc, Lucio Miele, Augusto Ochoa, Victoria Seewaldt, Shankar Subramaniam

School of Medicine Faculty Publications

Triple-negative breast cancer (TNBC) is a prevalent breast cancer subtype with the lowest 5-year survival. Several factors influence outcomes, but their inherent molecular and cellular heterogeneity are increasingly acknowledged as crucial determinants. Here, we report on the spatio-molecular heterogeneity underlying TNBC tumors in a retrospective, treatment-naive cohort with differential prognoses (17 good prognoses [GPx] >15-year survival and 15 poor prognoses [PPx] < 3-year survival]) profiled using GeoMx Digital Spatial Profiler. Analyses reveal that epithelial and microenvironment (TME) states are transcriptionally distinct between groups. Invasive GPx epithelia show an increase in immune transcripts, with a more immune-rich TME (via IF). PPx epithelia, in contrast, are more metabolically and translationally active, with a mesenchymal/fibrotic TME. Pre-cancerous epithelia in PPx exhibit a presence of aggressiveness, marked by increased EMT signaling and complement activity. We identify distinct epithelial gene signatures for PPx and GPx that can accurately classify diagnostic samples and likely inform therapy.

Post-Traumatic Rupture Of Primary Solid Pseudopapillary Epithelial Neoplasm (Spen) Of The Pancreas In A Male Adolescent: A Case Report, Paulo Castro, Heather Hartman, Yashasvi Shukla, Michael Moore, Dennis Drehner, Harish Lavu

Department of Surgery Faculty Papers

Introduction Solid pseudopapillary epithelial neoplasm (SPEN) is a rare pancreatic tumor that typically presents in adult women and is usually asymptomatic. Case presentation A 12-year-old male presented to the emergency department with worsening abdominal pain one day after suffering mild abdominal trauma during a soccer match. Physical exam showed diffuse abdominal tenderness and guarding. CT abdomen with IV contrast showed a heterogeneous, round structure adjacent to the pancreatic tail with mass effect upon the spleen. MRI abdomen revealed a “claw sign” of pancreatic tissue surrounding the structure, suggesting a an underlying pancreatic mass with capsular rupture measuring 8.3 x 8.1 …

Synergistic Anti-Tumor Activity Of Ciclopirox Olamine And Metformin In Triple-Negative Breast Cancer, Yakun Wu, Hui Lyu, Congcong Tan, Margaret E. Larsen, Shou Ching Tang, Shile Huang, Bolin Liu

School of Graduate Studies Faculty Publications

No abstract provided.

Accuracy Of Frozen Section For Hpv-Associated Squamous Cell Carcinoma Of Unknown Primary, Sindhura Sridhar, Annie Moroco, Shravan Gowrishankar, Mitra Mehrad, Kim Ely, James Lewis, Madalina Tuluc, Stacey Gargano, Melanie Hicks, Kyle Mannion, Arielle Thal, Adam Luginbuhl, Joseph Curry, David Cognetti, Michael Topf

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

INTRODUCTION: Current guidelines for the management of metastatic squamous cell carcinoma of unknown primary (SCCUP) recommend submission of suspicious primary sites for frozen section analysis (FSA). This study aims to investigate the diagnostic accuracy of FSA for identification of HPV-associated SCCUP.

METHODS: A retrospective cohort study of patients with biopsy-proven p16-positive SCCUP who underwent diagnostic operation at two tertiary care institutions was performed. Sensitivity, specificity, PPV, and NPV of diagnostic FSA were assessed.

RESULTS: 77 patients were included in analysis. 66 patients underwent definitive TORS (diagnostic TORS operation with subsequent neck dissection after identification of the occult primary tumor), 7 …

The Effects Of Bone-Remodeling Therapy On Survival, Pain, And Skeletal Related Events In The Setting Of Renal Cell Carcinoma With Bone Metastases: A Multicenter Investigation From A Large Global Health Research Network (Trinetx), Brian H. Im, Kevin K. Zarrabi, Aaron R. Hochberg, Mihir M. Shah, Md, James R. Mark, Joseph K. Izes, Patrick T. Gomella, Costas D. Lallas, Leonard G. Gomella, Adam R. Metwalli

Department of Urology Faculty Papers

INTRODUCTION: Renal cell carcinoma (RCC) is the most common renal malignancy-bone metastases (BM) are indicative of aggressive disease with a poor prognosis. We aim to evaluate the overall mortality of patients with RCC with and without BM, and to elucidate the effects of bone-remodeling therapy on mortality, incidence of skeletal-related events, and opioid usage patterns in patients with BM.

METHODS: A retrospective cohort study was conducted using TriNetX, a large, collaborative network sourced from electronic medical records of over 110 million patients from over 100 healthcare organizations. All adult patients with RCC and RCC with BM were queried.

RESULTS: There …

The Vascular Density/Angiogenesis Marker Cd31/Pecam1 Does Not Correlate With Overall Survival In Neuroendocrine Tumors, Nicholas J. Skill, Kenneth Avanzino, Yvette Bren-Mattison, J. Philip Boudreaux, Ramcharan Thiagarajan, Mary Maluccio

School of Medicine Faculty Publications

Abstract: Neuroendocrine neoplasms (NENs) are rare cancers. CD31/PECAM1 is an adhesion molecule that modulates endothelial cell-to-cell contact. Increased CD31 expression is a marker for tumor growth, and cancer aggressiveness. The purpose of this study was to better understand the prognostic value of CD31 expression in primary and metastatic NEN tumors in terms of correlations with overall survival and pathological metrics, tumor grade, and tumor primary/metastatic location. As NENs are highly vascular tumors, the hypothesis is that CD31 staining is an important prognostic biomarker and target. This is based on prior correlations between CD31 staining and 3-year recurrence-free survival in pancreas …

The Effect Of Neoadjuvant Chemoradiotherapy On Perioperative Outcomes In Rectal Cancer Patients Following Stoma Reversal-A Retrospective Cohort Analysis, Mary Junak, Rosemarie Turk, Mohammad Afaque Alam, Eli Thompson, David Schaub, Joseph Gunderson, Anesu S. Masango, Srikar Kollipara, Andrea Moreno, Daniom Tecle, Valentine N. Nfonsam

School of Medicine Faculty Publications

BACKGROUND: Anastomotic leak after reversal of an ostomy is a significant complication in rectal cancer patients. The effects of neoadjuvant chemoradiotherapy (NCRT) on outcomes following stoma reversal are not well established. The aim of our study was to evaluate the effect of NCRT on outcomes in rectal cancer patients following stoma reversal. METHODS: We performed a [2005-2012] retrospective cohort analysis of the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP), including adult (≥18 years) rectal cancer patients who had elective stoma reversal. Patients were stratified into those who received NCRT and those who did not. Primary outcomes were anastomotic …

Disruption Of Protein-Protein Interaction Hotspots In The C-Terminal Domain Of Mlh1 Confers Mismatch Repair Deficiency, Keri M. Fishwick, Diego Gomez Vieito, Giada Greco, Giulio Collotta, Marco Gatti, Anastasija A. Kulik, Raphaël Guérois, Ivan Corbeski, Ashutosh S. Phadte, Issam Senoussi, Petr Cejka, Anna Pluciennik, Antonio Porro, Alessandro A. Sartori

Department of Biochemistry and Molecular Biology Faculty Papers

MutLα, a heterodimer of MLH1 and PMS2, plays a key role in DNA mismatch repair (MMR), which maintains genomic stability by correcting replication errors. Loss of MLH1 function causes MMR deficiency (MMRd), leading to elevated mutation rates and increased cancer susceptibility. However, MMRd can offer a therapeutic advantage, as high tumour mutational burden enhances the efficacy of immune checkpoint inhibition. MMR also drives somatic expansion of CAG repeats linked to Huntington’s disease (HD) pathogenesis. The C-terminal domain (CTD) of MLH1 contains at least two distinct protein–protein interaction (PPI) sites. The S1 site supports heterodimerization with the PMS2 endonuclease, whereas the …

Inflammatory Co-Regulation Of Voltage-Gated Sodium Channels And Na,K-Atpase In Metastatic Breast Cancer, Steven D. Scahill, Kelly Jean Sherman, Dennis Paul

School of Graduate Studies Faculty Publications

Sodium regulation is a potentially major driver of cancer metastasis. Voltage-gated sodium channels (VGSCs) and Na,K-ATPase are sodium transporters that are upregulated in many advanced carcinomas and are implicated as metastatic drivers. However, little is known about what drives this overexpression, how these proteins influence metastatic behavior, or whether these complementary sodium transporters are co-regulated in cancer. Using sodium transporter regulation in healthy neurons as a model, the present study demonstrated that the inflammatory mediator tumor necrosis factor alpha (TNFα) affects the expression of VGSCs and Na,K-ATPase in an in vitro model of metastatic breast cancer. Acute TNFα challenge increased …

Metastatic Uveal Melanoma Surveillance: A Delphi Panel Consensus, Juan Alban, R. Christopher Bowen, David A. Reichstein, Meredith Mckean, Jose Lutzky, Ezekiel Weis, Richard D. Carvajal, Susan Dulka, Brian G. Morse, Marcus O. Butler, Suthee Rapisuwon, Kevin B. Kim, Sanjay Chandrasekaran, Allison Betof Warner, Jonathan S. Zager, Bartosz Chmielowski, Sapna P. Patel, Leonel Fernando Hernandez-Aya, Zelia M. Correa, Leslie A. Fecher, Yana G. Najjar, Kamaneh Montazeri, Alexander N. Shoushtari, Asad Javed, Dan S. Gombos, April K. S. Salama, Katy Tsai, Frank H. Miller, Nikhil Khushalani, Rino S. Seedor, Evan J. Lipson, Sunil A. Reddy, Elizabeth Buchbinder, Shailender Bhatia, Anna Pavlick, Inderjit Mehmi, Thomas Aaberg, Alexandra P. Ikeguchi, Ivana K. Kim, Scott D. Walter, Arun D. Singh, Ryan J. Sullivan, Jacob S. Choi, Basil K. Williams, Marlana Orloff, Prithvi Mruthyunjaya, Megan D. Schollenberger, Namita Gandhi, J. William Harbour, Sunandana Chandra

Department of Radiology Faculty Papers

BACKGROUND/OBJECTIVES: Uveal melanoma is a rare but aggressive intraocular malignancy that metastasizes in up to half of patients, most commonly to the liver, despite effective local treatment. In the absence of robust evidence, there are no standardized guidelines for post-treatment surveillance, resulting in wide variation in imaging modalities, frequency, and duration across physicians and institutions. This study aimed to develop expert consensus recommendations for surveillance strategies in patients with uveal melanoma.

METHODS: A modified Delphi method was conducted across three iterative survey rounds between September 2024 and February 2025 using an online platform. Panelists included medical oncologists, ocular oncologists, radiologists, …

Subgroup Analyses Of The Phase 3 Focus Study Of Melphalan/Hepatic Delivery System In Patients With Unresectable Metastatic Uveal Melanoma, Jonathan S. Zager, Marlana Orloff, Pier Francesco Ferrucci, Junsung Choi, David J. Eschelman, Evan S. Glazer, Aslam Ejaz, Erika Richtig, Sebastian Ochsenreither, Sunil A. Reddy, Michael C. Lowe, Georgia M. Beasley, Anja Gesierich, Martin Gschnell, Reinhard Dummer, Ana Arance, Stephen William Fenwick, Joseph J. Sacco, Johnny John, Matthew Wheater, Christian H. Ottensmeier

Department of Medical Oncology Faculty Papers

PURPOSE: To assess efficacy and safety in subgroups of patients treated with Melphalan/Hepatic Delivery System (melphalan/HDS), a drug/device combination for liver-directed treatment of metastatic UM (mUM) patients. Previously reported FOCUS study results indicated melphalan/HDS treatment provides a clinically meaningful response rate and favorable benefit-risk ratio in patients with unresectable mUM.

METHODS: Patients with mUM received treatment with melphalan (3.0 mg/kg ideal body weight) every 6-8 weeks for up to 6 cycles. Post hoc analyses of efficacy and safety were conducted for patient subgroups based on demographic and baseline disease characteristics.

RESULTS: 102 patients with mUM were enrolled; treatment was attempted …

Role Of Gut Microbiome In Oncogenesis And Oncotherapies, Renuka Sri Sai Peddireddi, Sai Kiran Kuchana, Rohith Kode, Saketh Khammammettu, Aishwarya Koppanatham, Supriya Mattigiri, Harshavardhan Gobburi, Suresh K. Alahari

School of Graduate Studies Faculty Publications

The gut microbiome has emerged as a key regulator of human health, influencing not only metabolism and immunity but also the development and treatment of cancer. Mounting evidence suggests that microbial dysbiosis contributes to oncogenesis by driving chronic inflammation, producing genotoxic metabolites, altering bile acid metabolism, and disrupting epithelial barrier integrity. At the same time, the gut microbiome significantly modulates the host response to oncotherapies including chemotherapy, radiotherapy, and especially immunotherapy, where microbial diversity and specific taxa determine treatment efficacy and toxicity. This review synthesizes current evidence on the role of the gut microbiome in both oncogenesis and oncotherapies, focusing …

Incidental Cardiac Metastasis In Breast Carcinoma, Yaomin Chen, Haibo Wang, Zhiyan Fu, Ellen Elizabeth Connor

School of Medicine Faculty Publications

Background and Clinical Significance: Metastatic breast cancer is a major global health burden, with common metastatic sites including the bones, lungs, liver, and brain. Cardiac metastasis is rare and often clinically silent, leading to underdiagnosis. Recognizing cardiac involvement, even when asymptomatic, is important for understanding the full extent of disease and ensuring optimal patient care. Case Presentation: We report the case of a woman with advanced breast carcinoma who showed no clinical or imaging evidence of cardiac involvement throughout the course of her illness. Following her death from progressive metastatic disease, an autopsy revealed metastatic carcinoma infiltrating the myocardium and …