Diseases Commons^™

Whole Genome And Reverse Protein Phase Array Landscapes Of Patient Derived Osteosarcoma Xenograft Models, Chia-Chin Wu, Licai Huang, Zhongting Zhang, Zhenlin Ju, Xingzhi Song, E Anders Kolb, Wendong Zhang, Jonathan Gill, Min Ha, Malcolm A Smith, Peter Houghton, Christopher L Morton, Raushan Kurmasheva, John Maris, Yael Mosse, Yiling Lu, Richard Gorlick, P Andrew Futreal, Hannah C Beird

Faculty, Staff and Student Publications

Osteosarcoma is the most common primary bone malignancy in children and young adults, and it has few treatment options. As a result, there has been little improvement in survival outcomes in the past few decades. The need for models to test novel therapies is especially great in this disease since it is both rare and does not respond to most therapies. To address this, an NCI-funded consortium has characterized and utilized a panel of patient-derived xenograft models of osteosarcoma for drug testing. The exomes, transcriptomes, and copy number landscapes of these models have been presented previously. This study now adds …

Inflammation, Physical Activity, And Disease-Free Survival In Stage Iii Colon Cancer: Calgb/Swog 80702 (Alliance), Justin C. Brown, Chao Ma, Qian Shi, Felix Couture, Philip Kuebler, Pankaj Kumar, Benjamin Tan, Smitha Krishnamurthi, Victor Chang, Richard M. Goldberg, Eileen M. O'Reilly, Anthony F. Shields, Jeffrey A. Meyerhardt

School of Medicine Faculty Publications

Background: Both inflammation and insufficient physical inactivity contribute to individual-level risk of disease recurrence and death in stage III colon cancer. The extent to which increased inflammatory risk can be offset by sufficient physical activity remains unknown. Methods: This cohort study was nested within the CALGB/SWOG 80702 (Alliance) randomized trial. Inflammatory burden was quantified by high-sensitivity C-reactive protein, interleukin-6, and soluble tumor necrosis factor-α receptor 2 after recovery from tumor resection. Physical activity was measured during and after postoperative chemotherapy. The primary endpoint was disease-free survival. Results: The 3-year disease-free survival rate was 88.4% among patients with low inflammation and …

Appropriateness Of Imaging For Low-Risk Prostate Cancer-Real World Data From The Pennsylvania Urologic Regional Collaboration (Purc), Raidizon Mercedes, Dennis Head, Elizabeth Zook, Eric Eidelman, Jeffrey Tomaszewski, Serge Ginzburg, Robert Uzzo, Marc Smaldone, John Danella, Thomas Guzzo, Daniel Lee, Laurence Belkoff, Jeffrey Walker, Adam Reese, Mihir Shah, Bruce Jacobs, Jay Raman

Einstein Health Papers

Imaging for prostate cancer defines the extent of disease. Guidelines recommend against imaging low-risk prostate cancer patients with a computed tomography (CT) scan or bone scan due to the low probability of metastasis. We reviewed imaging performed for men diagnosed with low-risk prostate cancer across the Pennsylvania Urologic Regional Collaborative (PURC), a physician-led data sharing and quality improvement collaborative. The data of 10 practices were queried regarding the imaging performed in men diagnosed with prostate cancer from 2015 to 2022. The cohort included 13,122 patients with 3502 (27%) low-risk, 2364 (18%) favorable intermediate-risk, 3585 (27%) unfavorable intermediate-risk, and 3671 (28%) …

Bp1003 Decreases Stat3 Expression And Its Pro-Tumorigenic Functions In Solid Tumors And The Tumor Microenvironment, Maria Gagliardi, Rhonda Kean, Bingbing Dai, Jithesh Augustine, Michael Roberts, Jason Fleming, D. Craig Hooper, Ana Ashizawa

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Overexpression and aberrant activation of signal transducer and activator of transcription 3 (STAT3) contribute to tumorigenesis, drug resistance, and tumor-immune evasion, making it a potential cancer therapeutic target. BP1003 is a neutral liposome incorporated with a nuclease-resistant P-ethoxy antisense oligodeoxynucleotide (ASO) targeting the STAT3 mRNA. Its unique design enhances BP1003 stability, cellular uptake, and target affinity. BP1003 efficiently reduces STAT3 expression and enhances the sensitivity of breast cancer cells (HER2⁺, triple negative) and ovarian cancer cells (late stage, invasive ovarian cancer) to paclitaxel and 5-fluorouracil (5-FU) in both 2D and 3D cell cultures. Similarly, ex vivo and in …

Factorial Trial To Optimize An Internet-Delivered Intervention For Sexual Health After Breast Cancer: Protocol For The Wf-2202 Sexual Health And Intimacy Enhancement (Shine) Trial, Kelly M. Shaffer, Jennifer Barsky Reese, Emily V. Dressler, Jillian V. Glazer, Wendy Cohn, Shayna L. Showalter, Anita H. Clayton, Suzanne C. Danhauer, Michelle Loch, Mai Kadi, Caleigh Smith, Kathryn E. Weaver, Glenn J. Lesser, Lee M. Ritterband

School of Medicine Faculty Publications

Background: Although most survivors of breast cancer report substantial sexual concerns following treatment, few receive support for these concerns. Delivering sexual health care to survivors of breast cancer via the internet could overcome many of the barriers to in-person treatment. Even when delivered remotely, survivor time constraints remain a leading barrier to sexual health intervention uptake. Objective: Guided by the multiphase optimization strategy methodological framework, the primary objective of this study is to identify the most efficient internet-delivered sexual health intervention package that is expected to provide survivors of breast cancer the greatest benefit with the fewest (and least-intensive) intervention …

Recurrent Inflammatory Myofibroblastic Tumor Of Larynx Harboring A Novel Thbs1::Alk Fusion, Namra Ajmal, Stacey Gargano, Ujwala Gosavi, Madalina Tuluc

Computational Medicine Center Faculty Papers

Inflammatory myofibroblastic tumor (IMT) is a rare soft tissue tumor primarily occurring in the abdominopelvic region of young patients, and it is characterized by spindle-shaped myofibroblasts, or fibroblasts surrounded by inflammatory infiltrate. Herein, we report a case of a 24-year-old male with a firm submucosal mass in the anterior right vocal fold diagnosed as an IMT that recurred 14 months later. The tumor demonstrated a novel THBS1::ALK fusion containing Exons 1-7 of the thrombospondin 1 (THBS1) gene fused to Exon 19 of the anaplastic lymphoma kinase (ALK) gene via next-generation sequencing with the NextSeq sequencer. The fusion of THBS1 to …

Personalized Neoantigen Vaccines As Early Intervention In Untreated Patients With Lymphoplasmacytic Lymphoma: A Non-Randomized Phase 1 Trial, Szymon J Szymura, Lin Wang, Tiantian Zhang, Soung-Chul Cha, Joo Song, Zhenyuan Dong, Aaron Anderson, Elizabeth Oh, Vincent Lee, Zhe Wang, Sapna Parshottam, Sheetal Rao, Jasper B Olsem, Brandon N Crumpton, Hans C Lee, Elisabet E Manasanch, Sattva Neelapu, Larry W Kwak, Sheeba K Thomas

Faculty, Staff and Student Publications

Lymphoplasmacytic lymphoma (LPL) is an incurable low-grade lymphoma with no standard therapy. Nine asymptomatic patients treated with a first-in-human, neoantigen DNA vaccine experienced no dose limiting toxicities (primary endpoint, NCT01209871). All patients achieve stable disease or better, with one minor response, and median time to progression of 72+ months. Post-vaccine single-cell transcriptomics reveal dichotomous antitumor responses, with reduced tumor B-cells (tracked by unique B cell receptor) and their survival pathways, but no change in clonal plasma cells. Downregulation of human leukocyte antigen (HLA) class II molecules and paradoxical upregulation of insulin-like growth factor (IGF) by the latter suggest resistance mechanisms. …

Association Between Agrichemical Mixtures And Pediatric Health Outcomes: Evidence From A Nebraska Population-Based Surveillance, Jabeen Taiba

Theses & Dissertations

Human exposure to environmental contaminants is associated with various pediatric health outcomes. Agrichemicals are a significant environmental risk factor for childhood cancers and congenital anomalies, and reduced exposure could improve pediatric health outcomes. Previous studies in Nebraska have explored the association between single pollutants and pediatric cancers and birth defects. However, it is important to estimate the overall effect of the agrichemical mixture on these pediatric health outcomes. In addition to environmental risk factors, several social vulnerability factors also contribute to increased agrichemical exposure and show disparities in pediatric cancers and birth defects. The objectives of this dissertation are to …

Understanding The Role Of Mastl In Colon Homeostasis And Colitis-Associated Cancer Development, Kristina Pravoverov

Theses & Dissertations

Colitis-associated cancer (CAC) is the most devastating complication of longstanding inflammatory bowel disease (IBD). Understanding the mechanisms underlying the switch from damage-repair to dysplasia in IBD is critical for identifying novel therapies to facilitate mucosal healing while mitigating CAC risk. Microtubule-associated serine-threonine kinase-like (MASTL), though crucial in cell growth and repair, is upregulated in sporadic colorectal cancer and CAC. This study sought to delineate the role of MASTL in colitis and CAC development.

First, we examined whether MASTL is associated with colitis and recovery. Review of publicly available data found significant elevation of MASTL and interleukin (IL)-22 in biopsies from …

The Dna Methylome Of Pediatric Brain Tumors Appears Shaped By Structural Variation And Predicts Survival, Fengju Chen, Yiqun Zhang, Lanlan Shen, Chad J Creighton

Faculty, Staff and Students Publications

Structural variation heavily influences the molecular landscape of cancer, in part by impacting DNA methylation-mediated transcriptional regulation. Here, using multi-omic datasets involving >2400 pediatric brain and central nervous system tumors of diverse histologies from the Children's Brain Tumor Network, we report hundreds of genes and associated CpG islands (CGIs) for which the nearby presence of somatic structural variant (SV) breakpoints is recurrently associated with altered expression or DNA methylation, respectively, including tumor suppressor genes ATRX and CDKN2A. Altered DNA methylation near enhancers associates with nearby somatic SV breakpoints, including MYC and MYCN. A subset of genes with SV-CGI methylation associations …

Comparative Plan Analysis: Helical Tomotherapy Vs. Linac Vmat For Lower Extremity Sarcomas, Marie E. Dibona

Masters Projects

Abstract

Introduction

Soft tissue sarcomas (STS) affect about 13,500 people annually in the United States, and those in the lower extremities present unique challenges in radiation therapy due to the wide variability in tumor sizes, sometimes exceeding 30cm. Traditional treatment involves C-Arm linear accelerators using Volumetric Modulated Radiation Therapy (VMAT), which provides precise targeting while sparing nearby organs. Helical Tomotherapy (HT) is another option, delivering radiation in a helical pattern with a binary MLC for a uniform dose distribution. However, no studies have compared VMAT and HT for lower extremity sarcomas of different sizes. This study aims to compare these …

Stanniocalcin 2 Governs Cancer Cell Adaptation To Nutrient Insufficiency Through Alleviation Of Oxidative Stress, Shuo Qie, Haijuan Xiong, Yaqi Liu, Chenhui Yan, Yalei Wang, Lifeng Tian, Chenguang Wang, Nianli Sang

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Solid tumours often endure nutrient insufficiency during progression. How tumour cells adapt to temporal and spatial nutrient insufficiency remains unclear. We previously identified STC2 as one of the most upregulated genes in cells exposed to nutrient insufficiency by transcriptome screening, indicating the potential of STC2 in cellular adaptation to nutrient insufficiency. However, the molecular mechanisms underlying STC2 induction by nutrient insufficiency and subsequent adaptation remain elusive. Here, we report that STC2 protein is dramatically increased and secreted into the culture media by Gln-/Glc- deprivation. STC2 promoter contains cis-elements that are activated by ATF4 and p65/RelA, two transcription factors activated by …

Renal Mass Imaging Modalities: Does Body Mass Index (Bmi) Matter?, Young Son, Mark E Quiring, Raeann M Dalton, Brian Thomas, Noah Davidson, Dayna Devincentz, Collin Payne, Sahil H Parikh, Benjamin A Fink, Thomas Mueller, Gordon Brown

Rowan-Virtua School of Osteopathic Medicine Departmental Research

PURPOSE: Accurate measurement of renal mass size is crucial in the management of renal cancer. With the burdensome cost of imaging yet its need for management, a better understanding of the variability among patients when determining mass size remains of urgent importance. Current guidelines on optimal imaging are limited, especially with respect to body mass index (BMI). The aim of this study is to discern which modalities accurately measure renal mass size and whether BMI influences such accuracy.

METHODS: A multi-institutional chart review was performed for adult patients undergoing partial or radical nephrectomy between 2018 and 2021, with 236 patients …

High-Dose Intravenous Vitamin C Combined With Docetaxel In Men With Metastatic Castration-Resistant Prostate Cancer: A Randomized Placebo-Controlled Phase Ii Trial, Channing Paller, Marianna Zahurak, Adel Mandl, Nicole Metri, Aliya Lalji, Elisabeth Heath, William Kelly, Christopher Hoimes, Pedro Barata, Jason Taksey, Dominique Garrison, Kartick Patra, Ginger Milne, Nicole Anders, Julie Nauroth, Jennifer Durham, Catherine Marshall, Mark Markowski, Mario Eisenberger, Emmanuel Antonarakis, Michael Carducci, Samuel Denmeade, Mark Levine

Department of Medicine Faculty Papers

UNLABELLED: High-dose intravenous vitamin C (HDIVC) administered to produce pharmacologic concentrations shows promise in preclinical models and small clinical trials, but larger prospective randomized trials are lacking. We evaluated the clinical benefit of combining HDIVC with docetaxel in patients with progressive metastatic castration-resistant prostate cancer (mCRPC). In this double-blind, placebo-controlled phase II trial, 47 patients were randomized 2:1 to receive docetaxel (75 mg/m2 i.v.) with either HDIVC (1 g/kg) or placebo. Coprimary endpoints were PSA50 response and adverse event rates. Secondary endpoints included overall survival, radiographic progression-free survival, and quality of life measured using the Functional Assessment of Cancer Therapy-Prostate …

Development Of Feature Extraction Models To Improve Image Analysis Applications In Cancer, Yu Shi

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

Cancer poses a significant global health challenge. With an estimated 20 million new cases diagnosed worldwide in 2022 and 9.7 million fatalities attributable to the disease, the economic burden of cancer is immense. It impacts healthcare systems and imposes substantial costs for its care on patients and their families. Despite advancements in early detection, prevention, and treatment that have reduced overall cancer mortality rates, the growing prevalence of cancer, particularly among younger individuals, remains a pressing issue.

Recent advancements in medical imaging technology have progressed significantly with the help of emerging computer vision and artificial intelligence (AI) technology. Despite these …

Exploring The Role Of The Arginine-Methylation Writer-Reader Pair Prmt5/Snd1 In Jak2-Mutant Myeloproliferative Neoplasms, Rocio Rubiano

Dissertations and Theses (Open Access)

Myeloproliferative neoplasms (MPNs) are a hematopoietic disease characterized by hyperproliferation of cells of the myeloid lineage for which current therapeutic options are limited. Discovered in 2005, the JAK2V617F mutation is the most common driver mutation in BCR-ABL negative MPNs, resulting in constitutive activation of the JAK2 protein and the JAK-STAT signaling pathway. A role for the methyltransferase activity of Protein Arginine Methyltransferase 5 (PRMT5) has been proposed in JAK2-mutant MPN, highlighting both a mechanism through which this mutation can drive disease progression and a potential mode of therapeutic intervention. Staphylococcal Nuclease Domain-Containing Protein 1 (SND1) is the effector molecule responsible …

Genetic Analysis Of Kmt2d Loss In Tumorigenesis Using Genetically Engineered Mouse Models, Yingda Jiang

Dissertations and Theses (Open Access)

The Cancer Genome Atlas Program (TCGA) has discovered multiple tumor suppressors that are commonly mutated across a variety of human cancers, such as chromatin regulators in COMPASS and SWI/SNF complexes. KMT2D, a histone H3K4 methyltransferase in the COMPASS complex, is frequently mutated in human lymphoma, melanoma, and epithelial carcinoma. Biochemically, KMT2D shapes the cellular enhancer landscape as the major writer of the putative enhancer mark H3K4me1. Given the critical role of cellular enhancer landscape in determining cellular lineage in embryonic development, it is unknown whether enhancer dysregulation caused by KMT2D loss leads lineage switch of tumor cells, which has …

Social Vulnerabilities In Head-Neck Melanoma Care: A Retrospective Cohort Study In The United States, Lillian Mccampbell, David Jun Fei-Zhang, Daniel Chelius, Ling-Lun Bob Hsia, Robert Dellavalle, Jill D'Souza, David Bentrem, Jeffrey Wayne, Jeffrey Rastatter, Anthony Sheyn

School of Medicine Faculty Publications

BACKGROUND: Studies addressing social determinants of health (SDH) in head-neck melanomas (HNM) have only assessed socioeconomic factor impact but not a wider scope of SDH. OBJECTIVE: Utilizing the Social Vulnerability Index (SVI), to assess the influence of specific SDH and their quantifiable associations with HNM management disparities across the varied community contexts in the United States. METHODS: This retrospective cohort study analyzed adults diagnosed with HNM from 1975 to 2017 from the Surveillance, Epidemiology, and End Results Program database. RESULTS: A total of 374,138 HNM in adults from 1975 to 2017 were assessed for disparities affiliated with increasing overall vulnerability/SVI …

A Retrospective Analysis Of Primary Breast Cancer Surgical Procedures (Mastectomy Versus Breast Conserving Surgery) Performed On Women Living In Rural And Urban Counties In South Carolina, Talitha M. Massaquoi

MUSC Theses and Dissertations

Women dealing with a diagnosis of breast cancer may be challenged when attempting to seek and obtain medical care while living in a rural community. It is not known whether geography impacts the decision-making process for women considering elective breast cancer surgery (mastectomy versus breast conserving surgery (BCS)) in South Carolina. We performed a retrospective analysis of breast cancer surgical options offered to women to examine if a difference exists in both rural and urban settings. Although there was a higher proportion of women in South Carolina who elected to undergo a mastectomy instead of BCS (4,416 [79.5%] vs. 1,139 …

Application Of Geographic Information Systems (Gis) In The Study Of Prostate Cancer Disparities: A Systematic Review, Christiane J. El Khoury

Department of Medical Oncology Faculty Papers

Introduction: PCa is one of the cancers that exhibits the widest disparity gaps. Geographical place of residence has been shown to be associated with healthcare access/utilization and PCa outcomes. Geographical Information Systems (GIS) are widely being utilized for PCa disparities research, however, inconsistencies in their application exist. This systematic review will summarize GIS application within PCa disparities research, highlight gaps in the literature, and propose alternative approaches. Methods: This paper followed the methods of the Cochrane Collaboration and the criteria set of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Articles published in peer-reviewed journals were searched through …

Impact Of Tumor Pigmentation In 6934 Patients With Uveal Melanoma At A Single Center, Samuel Goldstein, Ferris Bayasi, George Thomas, Matthew Barke, Michael Nguyen, Samantha Pastore, Carol Shields

Wills Eye Hospital Papers

Purpose: To evaluate clinical features and outcomes associated with degree of tumor pigmentation in patients with uveal melanoma (UM) of the choroid and ciliary body. Design: Retrospective observational study. Subjects: Six thousand nine hundred thirty-four consecutive patients with choroidal or ciliary body melanoma between 1971 and 2007 from a single ocular oncology center. Methods: Data on patient demographics, tumor characteristics, treatment approach, and clinical outcomes were collected. Comparisons between pigmented (>80% pigmentation by surface area), partially pigmented (20%–80%), and nonpigmented tumors (<20%) were performed using relevant hypothesis testing. Survival analyses for metastasis and melanoma-related death were conducted using the Kaplan–Meier method with log-rank tests for univariate comparisons. A multivariate Cox regression analysis was performed to assess the independent effects of multiple covariates on time-to-metastasis. Main Outcome Measures: Extraocular extension, ocular melanocytosis, time to tumor recurrence, tumor location, and melanoma-related metastasis and death. Results: There were 6934 eyes with UM and the degree of tumor pigmentation was classified as pigmented (n = 3762; 54%), partially pigmented (n = 2115; 31%), or nonpigmented (n = 1057; 15%). Pigmented UM was associated with extraocular extension (P < 0.001), ocular melanocytosis (P = 0.003), earlier tumor recurrence (P < 0.001), and more anterior tumor epicenter location (ciliary body, and equator to ora serrata) (P < 0.001). Pigmented UMs also exhibited the highest 10-year metastasis rate at 26%, compared with 19% for partially pigmented UMs and 16% for nonpigmented UMs (P < 0.001). Kaplan–Meier survival curves demonstrated differences among the tumor pigmentation groups for melanoma-related metastasis (P < 0.001) and melanoma-related death (P < 0.001). Multivariate Cox regression analysis for melanoma-related metastasis showed that pigmented UMs had a 29% higher relative risk of developing metastasis compared with partially pigmented UMs (P = 0.002) and a 54% higher relative risk of developing metastasis compared with nonpigmented UMs (P < 0.001). Conclusions: Pigmented choroidal and ciliary body melanoma is more often associated with ocular melanocytosis, extraocular extension, anterior tumor epicenter, and earlier tumor recurrence. We also revealed that patients with pigmented UMs demonstrate a higher 10-year rate of metastatic disease and have decreased metastatic survival relative to partially pigmented and nonpigmented UMs. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Transcriptomic Features Associated To Neoadjuvant Chemotherapy Response In Four Molecular Breast Cancer Subtypes, Hedda Michelle Guevara-Nieto, Rafael Parra-Medina, Carlos Alberto Orozca, Alejandro Mejia-Garcia, Jovanny Zabaleta, Liliana Lopez-Kleine, Alba Lucia Combita-Rojas

School of Medicine Faculty Publications

12th Annual Symposium on Global Cancer Research, Virtual, May 5 - 9, 2024

Exposure To Light At Night And Risk Of Cancer: A Systematic Review, Meta-Analysis, And Data Synthesis, Samuel Ma, Yossef Alsabawi, Hashem B El-Serag, Aaron P Thrift

Faculty, Staff and Students Publications

BACKGROUND: Emerging interest surrounds the role of environmental factors, notably exposure to light at night (LAN), as a potential cause of cancer. The aim of this study was to conduct a systematic review and, if possible, meta-analysis of observational studies on LAN and cancer risk of multiple types.

METHODS: A systematic literature search in PubMed, Web of Science, and Embase, spanning from inception to May 2023, was conducted. Studies focusing on the association between LAN exposure and cancer risk in adult populations were included. We used random effects models to calculate pooled risk estimates (RR) and 95% confidence intervals (CI). …

Genome-Wide Methylation Patterns In Primary Uveal Melanoma: Development Of Methylsig-Um, An Epigenomic Prognostic Signature To Improve Patient Stratification, Emilie Lalonde, Dong Li, Kathryn Ewens, Carol L. Shields, Arupa Ganguly

Wills Eye Hospital Papers

Despite studies highlighting the prognostic utility of DNA methylation in primary uveal melanoma (pUM), it has not been translated into a clinically useful tool. We sought to define a methylation signature to identify newly diagnosed individuals at high risk for developing metastasis. Methylation profiling was performed on 41 patients with pUM with stage T2-T4 and at least three years of follow-up using the Illumina Infinium HumanMethylation450K BeadChip (N = 24) and the EPIC BeadChip (N = 17). Findings were validated in the TCGA cohort with known metastatic outcome (N = 69). Differentially methylated probes were identified in patients who developed …

Onecut2 Acts As A Lineage Plasticity Driver In Adenocarcinoma As Well As Neuroendocrine Variants Of Prostate Cancer, Chen Qian, Qian Yang, Mirja Rotinen, Rongrong Huang, Hyoyoung Kim, Brad Gallent, Yiwu Yan, Radu M Cadaneanu, Baohui Zhang, Salma Kaochar, Stephen J Freedland, Edwin M Posadas, Leigh Ellis, Dolores Di Vizio, Colm Morrissey, Peter S Nelson, Lauren Brady, Ramachandran Murali, Moray J Campbell, Wei Yang, Beatrice S Knudsen, Elahe A Mostaghel, Huihui Ye, Isla P Garraway, Sungyong You, Michael R Freeman

Faculty, Staff and Students Publications

Androgen receptor- (AR-) indifference is a mechanism of resistance to hormonal therapy in prostate cancer (PC). Here we demonstrate that ONECUT2 (OC2) activates resistance through multiple drivers associated with adenocarcinoma, stem-like and neuroendocrine (NE) variants. Direct OC2 gene targets include the glucocorticoid receptor (GR; NR3C1) and the NE splicing factor SRRM4, which are key drivers of lineage plasticity. Thus, OC2, despite its previously described NEPC driver function, can indirectly activate a portion of the AR cistrome through epigenetic activation of GR. Mechanisms by which OC2 regulates gene expression include promoter binding, enhancement of genome-wide chromatin accessibility, and super-enhancer reprogramming. Pharmacologic …

Assessing Breast Disease With Deep Learning Model Using Bimodal Bi-View Ultrasound Images And Clinical Information, Fengping Liang, Yihua Song, Xiaoping Huang, Tong Ren, Qiao Ji, Yanan Guo, Xiang Li, Yajuan Sui, Xiaohui Xie, Lanqing Han, Yuanqing Li, Yong Ren, Zuofeng Xu

Faculty, Staff and Students Publications

Breast cancer is the second leading cause of carcinoma-linked death in women. We developed a multi-modal deep-learning model (BreNet) to differentiate breast cancer from benign lesions. BreNet was constructed and trained on 10,108 images from one center and tested on 3,762 images from two centers in three steps. The diagnostic ability of BreNet was first compared with that of six radiologists; a BreNet-aided scheme was constructed to improve the diagnostic ability of the radiologists; and the diagnosis of real-world radiologists' scheme was then compared with the BreNet-aided scheme. The diagnostic performance of BreNet was superior to that of the radiologists …

Enhancing Neoadjuvant Virotherapy's Effectiveness By Targeting Stroma To Improve Resectability In Pancreatic Cancer, Khandoker Usran Ferdous, Mulu Z. Tesfay, Aleksandra Cios, Randal S. Shelton, Conner Hartupee, Alicja Urbaniak, Jean Christopher Chamcheu, Michail N. Mavros, Emmanouil Giorgakis, Bahaa Mustafa, Camila C. Simoes, Isabelle R. Miousse, Alexei G. Basnakian, Omeed Moaven, Steven R. Post, Martin J. Cannon, Thomas Kelly, Bolni Marius Nagalo

School of Medicine Faculty Publications

About one-fourth of patients with pancreatic ductal adenocarcinoma (PDAC) are categorized as borderline resectable (BR) or locally advanced (LA). Chemotherapy and radiation therapy have not yielded the anticipated outcomes in curing patients with BR/LA PDAC. The surgical resection of these tumors presents challenges owing to the unpredictability of the resection margin, involvement of vasculature with the tumor, the likelihood of occult metastasis, a higher ratio of positive lymph nodes, and the relatively larger size of tumor nodules. Oncolytic virotherapy has shown promising activity in preclinical PDAC models. Unfortunately, the desmoplastic stroma within the PDAC tumor microenvironment establishes a barrier, hindering …

Health Disparities In Cervical Cancer: Estimating Geographic Variations Of Disease Burden And Association With Key Socioeconomic And Demographic Factors In The Us, Tara Castellano, Andrew K. Elhabr, Christina Washington, Jie Ting, Yitong J. Zhang, Fernanda Musa, Ezgi Berksoy, Kathleen Moore, Leslie Randall, Jagpreet Chhatwal, Turgay Ayer, Charles A. Leath

School of Medicine Faculty Publications

BACKGROUND: Despite advances in cervical cancer (CC) prevention, detection, and treatment in the US, health disparities persist, disproportionately affecting underserved populations or regions. This study analyzes the geographical distribution of both CC and recurrent/metastatic CC (r/mCC) in the US and explores potential risk factors of higher disease burden to inform potential strategies to address disparities in CC and r/mCC. METHODS: We estimated CC screening rates, as well as CC burden (number of patients with CC diagnosis per 100,000 eligible enrollees) and r/mCC burden (proportion of CC patients receiving systemic therapy not in conjunction with surgery or radiation), at the geographic …

Central Nervous System Prophylaxis Utilization In Patients With Newly Diagnosed Diffuse Large B-Cell Lymphoma Within A Large Community Health System, Michael J. Williams, Sol D. Atienza, Renee H. Aranda, Kayleigh B. Flint, Sherjeel Sana, Stephen C. Medlin, Zartash Gul, Federico A. Sanchez, Michael A. Thompson

Journal of Patient-Centered Research and Reviews

Purpose: The impact of central nervous system (CNS) prophylaxis in diffuse large B-cell lymphoma (DLBCL) is contentious. The CNS International Prognostic Index (IPI) calculator offers prognostic guidance in identifying those patients who may be at highest risk of disease progression or relapse to the CNS. However, it is unclear whether this tool has guided clinician decision-making in a real-world setting. Studies have suggested that CNS prophylaxis may not offer clinically significant benefit in terms of preventing CNS disease progression. Given this, we investigated the utilization of CNS prophylaxis within our own population and documentation of the CNS-IPI score.

Methods: We …

Coexistence Of Large Cell Transformed Mycosis Fungoides And Diffuse Large B-Cell Lymphoma In One Patient, Thomas Z. Rohan, Jayson Suriano, Volkan Tekmen, Safiyyah Bhatti, Sahithi Talasila, Daniel Joffe, Caleb Holtmeyer, Jason B. Lee, Onder Alpdogan, Neda Nikbakht

Department of Dermatology and Cutaneous Biology Faculty Papers

Diffuse large B-cell lymphoma (DLBCL) is the most common and aggressive subtype of non-Hodgkin lymphoma. The overall risk of developing DLBCL is increased in patients with other lymphomas, such as mycosis fungoides (MF). In this report, we present an 81-year-old female with early-stage MF who simultaneously progressed to tumor stage, large-cell transformed (LCT) MF and developed a primary DLBCL in a lymph node (LN). She presented with a tumor on her leg and new lymphadenopathy in her right axilla. Skin biopsy of the tumor revealed infiltration of large atypical CD3+, CD4+, and CD30+ cells, and a smaller portion of CD8+ …