Neoplasms Commons^™

Utility Of Pre-Procedural [99mtc]Tcmaa Spect/Ct Multicompartment Dosimetry For Treatment Planning Of 90y Glass Microspheres In Patients With Hepatocellular Carcinoma: Comparison Of Anatomic Versus [99mtc]Tcmaa-Based Segmentation, Marnix Lam, Etienne Garin, Paul Haste, Alban Denys, Brian Geller, S Cheenu Kappadath, Cuneyt Turkmen, Daniel Y Sze, Hamad Saleh Alsuhaibani, Ken Herrmann, Marco Maccauro, Murat Cantasdemir, Matthew Dreher, Kirk D Fowers, Vanessa Gates, Riad Salem

Faculty, Staff and Student Publications

Purpose: Pre-treatment [99mTc]TcMAA-based radioembolization treatment planning using multicompartment dosimetry involves the definition of the tumor and normal tissue compartments and calculation of the prescribed absorbed doses. The aim was to compare the real-world utility of anatomic and [99mTc]TcMAA-based segmentation of tumor and normal tissue compartments.

Materials and methods: Included patients had HCC treated by glass [90Y]yttrium microspheres, ≥ 1 tumor, ≥ 3 cm diameter and [99mTc]TcMAA SPECT/CT imaging before treatment. Segmentation was performed retrospectively using dedicated dosimetry software: (1) anatomic (diagnostic CT/MRI-based), and (2) [99mTc]TcMAA threshold-based (i.e., using an activity-isocontour threshold). CT/MRI was co-registered with [99mTc]TcMAA SPECT/CT. Logistic regression and …

Psychometric Properties And Meaningful Change Thresholds For The Qol-E Instrument In Patients With Myelodysplastic Neoplasms, Esther Natalie Oliva, Shien Guo, Jennifer Lord-Bessen, Aylin Yucel, Roberto Latagliata, Massimo Breccia, Giuseppe A Palumbo, Grazia Sanpaolo, Marta Riva, Valeria Santini, Uwe Platzbecker, Guillermo Garcia-Manero, Pierre Fenaux, Christopher G Pelligra

Faculty, Staff and Student Publications

peripheral blood cytopenias, and an increased risk of progression to acute myeloid leukemia. One of the main treatment goals is improving quality of life (QoL), particularly for patients with lower-risk MDS (LR-MDS) who may live longer with compromised QoL. The QOL-E© is a patient-reported outcome (PRO) measure specifically developed to address the lack of a health-related QoL questionnaire for patients with MDS. The objective of this study was to evaluate the psychometric performance of the QOL-E in patients with LR-MDS.

Methods: Data from four clinical trials in MDS (MEDALIST, DARB-MDS, EQoL-MDS, and RevMDS trials) were used to assess construct validity, …

Predicting Sinonasal Inverted Papilloma Attachment Using Machine Learning: Current Lessons And Future Directions, Sean P Mckee, Xiaomin Liang, William C Yao, Brady Anderson, Jumah G Ahmad, David Z Allen, Salman Hasan, Andy J Chua, Chinmay Mokashi, Samia Islam, Amber U Luong, Martin J Citardi, Luca Giancardo

Faculty, Staff and Student Publications

Background: Hyperostosis is a common radiographic feature of inverted papilloma (IP) tumor origin on computed tomography (CT). Herein, we developed a machine learning (ML) model capable of analyzing CT images and identifying IP attachment sites.

Methods: A retrospective review of patients treated for IP at our institution was performed. The tumor attachment site was manually segmented on CT scans by the operating surgeon. We used a nnU-Net model, a state-of-the-art deep learning-based segmentation algorithm that automatically configures image preprocessing, network architecture, training, and post-processing to identify the IP attachment site. The model was trained and evaluated using a 5-fold cross …

Tissue And Imaging Biomarkers Of Response To Neoadjuvant Nivolumab Or Nivolumab Plus Ipilimumab In Patients With Resectable Hepatocellular Carcinoma, Michael Lapelusa, Shadi Chamseddine, Hop Sanderson Tran Cao, Lianchun Xiao, Elshad Hasanov, Priya Bhosale, Hesham M Amin, Yehia I Mohamed, Betul Gok Yavuz, Yara Sakr, Li Xu, Ian Hu, Sunyoung S Lee, Divya Sakamuri, Sonali Jindal, Van Nguyen, Michael A Curran, Ryan Sun, Asif Rashid, Dan Gabriel Duda, Padmanee Sharma, Aliya Qayyum, Ahmed Omar Kaseb

Faculty, Staff and Student Publications

Introduction: Perioperative immunotherapy has shown promise in some patients with early-stage hepatocellular carcinoma (HCC). This study examined tissue and imaging biomarkers associated with pathologic response in a phase II clinical trial in patients with resectable HCC.

Methods: Analysis included 18 patients with biopsy-proven resectable HCC treated with neoadjuvant nivolumab plus ipilimumab or nivolumab alone in a phase II clinical trial at MD Anderson Cancer Center (NCT03222076). Liver MRE (to measure tissue fibrosis) and biopsies (to evaluate immune activation markers) were obtained serially pretreatment and after completing neoadjuvant immunotherapy. A major pathologic response (MPR) was defined as tumor necrosis …

Knowledge-Based Planning For Fully Automated Radiation Therapy Treatment Planning Of 10 Different Cancer Sites, Christine V Chung, Meena S Khan, Adenike Olanrewaju, Mary Pham, Quyen T Nguyen, Tina Patel, Prajnan Das, Michael S O'Reilly, Valerie K Reed, Anuja Jhingran, Hannah Simonds, Ethan B Ludmir, Karen E Hoffman, Komeela Naidoo, Jeannette Parkes, Ajay Aggarwal, Lauren L Mayo, Shalin J Shah, Chad Tang, Beth M Beadle, Julie Wetter, Gary Walker, Simon Hughes, Vinod Mullassery, Stephen Skett, Christopher Thomas, Lifei Zhang, Son Nguyen, Raymond P Mumme, Raphael J Douglas, Hana Baroudi, Laurence E Court

Faculty, Staff and Student Publications

Purpose: Radiation treatment planning is highly complex and can have significant inter- and intra-planner inconsistency, as well as variability in planning time and plan quality. Knowledge-based planning (KBP) is a tool that can be used to efficiently produce high-quality, consistent, clinically acceptable plans, independent of planner skills and experience. In this study, we created and validated multiple clinically acceptable and fully automatable KBP models, with the goal of creating VMAT plans without user intervention.

Methods: Ten KBP models were configured using high quality clinical plans from a single institution. They were then honed to be part of a fully automatable …

The Role Of Epigenetic Aberrations In The Cold Tumor Phenotype And Inflammatory Signaling In High-Risk Neuroblastoma, Pamela Morgan Watson

Alternative Theses and Dissertations (AETDs)

Neuroblastoma (NB) is a highly aggressive, heterogeneous disease that arises from the sympathetic nervous system (SNS) and originates from neural crest cells (NCCs) (1). NB is the most common extracranial cancer in pediatric accounts for 15% of pediatric cancer deaths (2). This high mortality rate is the result of the metastatic, immune evasive, and treatment resistant characteristics of the disease (3). It has been proposed that NB arises from blocks in differentiation during development, resulting in a mixture of two distinct cell types within the tumor: mesenchymal and adrenergic (Figure 1.1) (4,5). The adrenergic cell type is more differentiated, and …

Nuclear Expression Of Dynamin 2 Is Associated With Tumor Aggressiveness In Bladder Cancer Patients: A Bioinformatics And Experimental Approach, Mahdieh Razmi, Leili Saeednejad Zanjani, Mandana Rahimi, Roya Sajed, Sadegh Safaei, Zahra Madjd, Roya Ghods

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Dynamin 2 (DNM2) is aberrantly expressed in different malignancies and exerts a function in tumor progression.

AIMS: This study, for the first time, aimed to evaluate the clinical and prognostic value of DNM2 in the pathophysiology of bladder cancer using bioinformatics analysis and experimental evaluation.

METHODS AND RESULTS: We analyzed gene expression of DNM2 in bladder tumor by GEPIA2 and GENT2 platforms. Cluster subnetworks were recognized from the protein-protein interaction (PPI) network using the MCODE plugin to screen the key genes. Subsequently, the pathway enrichment analysis was evaluated. Then, the immunohistochemical examination was conducted on 209 paraffin-embedded bladder cancer …

Micrornas Are Enriched At Covid-19 Genomic Risk Regions, And Their Blood Levels Correlate With The Covid-19 Prognosis Of Cancer Patients Infected By Sars-Cov-2, Simone Anfossi, Faezeh Darbaniyan, Joseph Quinlan, Steliana Calin, Masayoshi Shimizu, Meng Chen, Paola Rausseo, Michael Winters, Elena Bogatenkova, Kim-Anh Do, Ivan Martinez, Ziyi Li, Loredana Antal, Tudor Rares Olariu, Ignacio Wistuba, George A Calin

Faculty, Staff and Student Publications

Background: Cancer patients are more susceptible to an aggressive course of COVID-19. Developing biomarkers identifying cancer patients at high risk of COVID-19-related death could help determine who needs early clinical intervention. The miRNAs hosted in the genomic regions associated with the risk of aggressive COVID-19 could represent potential biomarkers for clinical outcomes.

Patients and methods: Plasma samples were collected at The University of Texas MD Anderson Cancer Center from cancer patients (N = 128) affected by COVID-19. Serum samples were collected from vaccinated healthy individuals (n = 23) at the Municipal Clinical Emergency Teaching Hospital in Timisoara, Romania. An in …

Assessing Influence Of Mismatch Repair Mutations On Survival In Patients After Resection Of Pancreatic Ductal And Periampullary Adenocarcinoma, Elizabeth Prezioso, Eleanor Mancheski, Kylee Shivok, Zachary Kaplan, Wilbur Bowne, Aditi Jain, Harish Lavu, Charles Yeo, Avinoam Nevler

Kimmel Cancer Center Faculty Papers

Background: Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related deaths in the United States. Previous studies have indicated that microsatellite instability and deficient mismatch repair (MMR) may be associated with improved survival in patients with pancreatic cancer. Here, we aim to investigate the impact of deficient MMR (dMMR) status on oncologic outcomes in patients after resection of PDAC and periampullary adenocarcinoma. Methods: This is a single-institution, retrospective study based on a prospectively maintained database. Pancreatic ductal adenocarcinoma (N = 342) and periampullary adenocarcinoma patients (N = 76) who underwent pancreatic resection surgery between 2016 and 2021 were …

Neoadjuvant Parpi Or Chemotherapy In Ovarian Cancer Informs Targeting Effector Treg Cells For Homologous-Recombination-Deficient Tumors, Yikai Luo, Yu Xia, Dan Liu, Xiong Li, Huayi Li, Jiahao Liu, Dongchen Zhou, Yu Dong, Xin Li, Yiyu Qian, Cheng Xu, Kangjia Tao, Guannan Li, Wen Pan, Qing Zhong, Xingzhe Liu, Sen Xu, Zhi Wang, Ronghua Liu, Wei Zhang, Wanying Shan, Tian Fang, Siyuan Wang, Zikun Peng, Ping Jin, Ning Jin, Shennan Shi, Yuxin Chen, Mengjie Wang, Xiaofei Jiao, Mengshi Luo, Wenjian Gong, Ya Wang, Yue Yao, Yi Zhao, Xinlin Huang, Xuwo Ji, Zhaoren He, Guangnian Zhao, Rong Liu, Mingfu Wu, Gang Chen, Li Hong, Cocpo Consortium, Ding Ma, Yong Fang, Han Liang, Qinglei Gao

Faculty, Staff and Student Publications

Homologous recombination deficiency (HRD) is prevalent in cancer, sensitizing tumor cells to poly (ADP-ribose) polymerase (PARP) inhibition. However, the impact of HRD and related therapies on the tumor microenvironment (TME) remains elusive. Our study generates single-cell gene expression and T cell receptor profiles, along with validatory multimodal datasets from >100 high-grade serous ovarian cancer (HGSOC) samples, primarily from a phase II clinical trial (NCT04507841). Neoadjuvant monotherapy with the PARP inhibitor (PARPi) niraparib achieves impressive 62.5% and 73.6% response rates per RECIST v.1.1 and GCIG CA125, respectively. We identify effector regulatory T cells (eTregs) as key responders to HRD …

Landmark-Based Auto-Contouring Of Clinical Target Volumes For Radiotherapy Of Nasopharyngeal Cancer, Carlos Sjogreen, Tucker J Netherton, Anna Lee, Moaaz Soliman, Skylar S Gay, Callistus Nguyen, Raymond Mumme, Ivan Vazquez, Dong Joo Rhee, Carlos E Cardenas, Mary K Martel, Beth M Beadle, Laurence Edward Court

Faculty, Staff and Student Publications

Background: The delineation of clinical target volumes (CTVs) for radiotherapy for nasopharyngeal cancer is complex and varies based on the location and extent of disease.

Purpose: The current study aimed to develop an auto-contouring solution following one protocol guidelines (NRG-HN001) that can be adjusted to meet other guidelines, such as RTOG-0225 and the 2018 International guidelines.

Methods: The study used 2-channel 3-dimensional U-Net and nnU-Net framework to auto-contour 27 normal structures in the head and neck (H&N) region that are used to define CTVs in the protocol. To define the CTV-Expansion (CTV1 and CTV2) and CTV-Overall (the outer envelope of …

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

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 …

Breast Cancer (Bc) And Severe Covid-19 (C-19) Outcomes: A Matched Analysis, Marija Sullivan, Xiudong Lei, Sharon H Giordano, Mariana Chavez-Macgregor

Faculty, Staff and Student Publications

Purpose: Patients with cancer receiving anticancer treatment have a higher risk of severe COVID-19 (C-19) outcomes. We examine the association between breast cancer (BC), recent treatment (systemic therapy, surgery, radiation), and C-19 outcomes.

Methods: Retrospective matched cohort study using the Optum® de-identified C-19 Electronic Health Record dataset (2007-2022). Patients with C-19 were categorized into: no cancer, BC with recent treatment, and BC without recent treatment and matched based on age, C-19 diagnosis date, and comorbidity score. We evaluated 30-day mortality, mechanical ventilation, intensive care unit (ICU) stay, and hospitalization. A composite outcome including all outcomes was analyzed. Multivariable logistic regression …

Loss Of Hormone Receptor Expression After Exposure To Fluid Shear Stress In Breast Cancer Cell Lines, Jonathan Cuccia, Braulio Andres Ortega Quesada, Ethan P. Littlefield, Alejandra M. Ham, Matthew E. Burow, Adam T. Melvin, Elizabeth C. Martin

School of Medicine Faculty Publications

Following metastatic spread, many hormone receptor positive (HR(+)) patients develop a more aggressive phenotype with an observed loss of the HRs estrogen receptor (ER) and progesterone receptor (PR). During metastasis, breast cancer cells are exposed to high magnitudes of fluid shear stress (FSS). Unfortunately, the role for FSS on the regulation of HR expression and function during metastasis is not fully understood. This study was designed to elucidate the impact of FSS on HR(+) breast cancer. Utilizing a microfluidic platform capable of exposing breast cancer cells to FSS that mimics in situ conditions, we demonstrate the impact of FSS exposure …

An Essential Gene Signature Of Breast Cancer Metastasis Reveals Targetable Pathways, Yiqun Zhang, Fengju Chen, Marija Balic, Chad J Creighton

Faculty, Staff and Students Publications

BACKGROUND: The differential gene expression profile of metastatic versus primary breast tumors represents an avenue for discovering new or underappreciated pathways underscoring processes of metastasis. However, as tumor biopsy samples are a mixture of cancer and non-cancer cells, most differentially expressed genes in metastases would represent confounders involving sample biopsy site rather than cancer cell biology.

METHODS: By paired analysis, we defined a top set of differentially expressed genes in breast cancer metastasis versus primary tumors using an RNA-sequencing dataset of 152 patients from The Breast International Group Aiming to Understand the Molecular Aberrations dataset (BIG-AURORA). To filter the genes …

Development Of A Novel Comprehensive Hepatocellular Carcinoma Outcome Prognostic Scoring System With Integration Of Imaging Features, Hop S Tran Cao, Russell G Witt, Khaled M Elsayes, Ali A Baiomy, Lianchun Xiao, Sarah Palmquist, Sunyoung S Lee, Yehia I Mohamed, Armeen Mahvash, Ching-Wei D Tzeng, Yun Shin Chun, Eugene Jon Koay, Asif Rashid, Manal M Hassan, James C Yao, Jean-Nicolas Vauthey, Ahmed O Kaseb

Faculty, Staff and Student Publications

Background: Accurate prognostic stratification of hepatocellular carcinoma (HCC) is vital for clinical trial enrollment and treatment allocation. Multiple scoring systems have been created to predict patient survival, but no standardized scoring systems account for radiologic tumor features. We sought to create a generalizable scoring system for HCC which incorporates standardized radiologic tumor features and more accurately predicts overall survival (OS) than established systems.

Methods: Clinicopathologic parameters were collected from a prospectively collected cohort of patients with HCC treated at a single institution. Imaging studies were evaluated for tumor characteristics. Patients were randomly divided into a training set for identification of …

Focal Adhesion Kinase-Yap Signaling Axis Drives Drug-Tolerant Persister Cells And Residual Disease In Lung Cancer, Franziska Haderk, Yu-Ting Chou, Lauren Cech, Celia Fernández-Méndez, Johnny Yu, Victor Olivas, Ismail M Meraz, Dora Barbosa Rabago, D Lucas Kerr, Carlos Gomez, David V Allegakoen, Juan Guan, Khyati N Shah, Kari A Herrington, Oghenekevwe M Gbenedio, Shigeki Nanjo, Mourad Majidi, Whitney Tamaki, Yashar K Pourmoghadam, Julia K Rotow, Caroline E Mccoach, Jonathan W Riess, J Silvio Gutkind, Tracy T Tang, Leonard Post, Bo Huang, Pilar Santisteban, Hani Goodarzi, Sourav Bandyopadhyay, Calvin J Kuo, Jeroen P Roose, Wei Wu, Collin M Blakely, Jack A Roth, Trever G Bivona

Faculty, Staff and Student Publications

Targeted therapy is effective in many tumor types including lung cancer, the leading cause of cancer mortality. Paradigm defining examples are targeted therapies directed against non-small cell lung cancer (NSCLC) subtypes with oncogenic alterations in EGFR, ALK and KRAS. The success of targeted therapy is limited by drug-tolerant persister cells (DTPs) which withstand and adapt to treatment and comprise the residual disease state that is typical during treatment with clinical targeted therapies. Here, we integrate studies in patient-derived and immunocompetent lung cancer models and clinical specimens obtained from patients on targeted therapy to uncover a focal adhesion kinase (FAK)-YAP signaling …

Mortality After Major Cardiovascular Events In Survivors Of Childhood Cancer, Wendy Bottinor, Cindy Im, David R Doody, Saro H Armenian, Alexander Arynchyn, Borah Hong, Rebecca M Howell, David R Jacobs, Kirsten K Ness, Kevin C Oeffinger, Alexander P Reiner, Gregory T Armstrong, Yutaka Yasui, Eric J Chow

Faculty, Staff and Student Publications

Background: Adult survivors of childhood cancer are at risk for cardiovascular events.

Objectives: In this study, we sought to determine the risk for mortality after a major cardiovascular event among childhood cancer survivors compared with noncancer populations.

Methods: All-cause and cardiovascular cause-specific mortality risks after heart failure (HF), coronary artery disease (CAD), or stroke were compared among survivors and siblings in the Childhood Cancer Survivor Study (CCSS) and participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Cox proportional hazard regression models were used to estimate HRs and 95% CIs between groups, adjusted for demographic and clinical …

Pan-Cancer Genomic Characterization Of Human Papillomavirus Associated Tumors, Jeremiah Ray Holt

Theses and Dissertations (ETD)

Infection with high-risk human papillomavirus (HPV) accounts for nearly all cervical cancers (CESC), a subset of other anogenital squamous cancers, and increasing rates of head and neck squamous cell carcinomas (HNSC), with each cancer type having heterogenous outcomes due to a general lack of personalized care. Large scale genomic analyses have catalogued the somatic alterations occurring frequently among squamous tumor types including HNSC and CESC, but few studies have incorporated a thorough analysis of HPV genomics. High-risk HPVs are double-stranded DNA (dsDNA) viruses capable of integrating their genomes into host chromosomes, a phenomenon known to promote HPV-associated cancer formation. HPV …

Steroid Receptor Coactivators In Treg And Th17 Cell Biology And Function, Yosi Gilad, Ortal Shimon, Sang Jun Han, David M Lonard, Bert W O'Malley

Faculty, Staff and Students Publications

Steroid receptor coactivators (SRCs) are master regulators of transcription that play key roles in human physiology and pathology. SRCs are particularly important for the regulation of the immune system with major roles in lymphocyte fate determination and function, macrophage activity, regulation of nuclear factor κB (NF-κB) transcriptional activity and other immune system biology. The three members of the p160 SRC family comprise a network of immune-regulatory proteins that can function independently or act in synergy with each other, and compensate for - or moderate - the activity of other SRCs. Recent evidence indicates that the SRCs are key participants in …

Single-Cell Dissection Of Tumor Microenvironmental Response And Resistance To Cancer Therapy, Yikai Luo, Han Liang

Faculty, Staff and Student Publications

Cancer treatment strategies have evolved significantly over the years, with chemotherapy, targeted therapy, and immunotherapy as major pillars. Each modality leads to unique treatment outcomes by interacting with the tumor microenvironment (TME), which imposes a fundamental selective pressure on cancer progression. The advent of single-cell profiling technologies has revolutionized our understanding of the intricate and heterogeneous nature of the TME at an unprecedented resolution. This review delves into the commonalities and differential manifestations of how cancer therapies reshape the microenvironment in diverse cancer types. We highlight how groundbreaking immune checkpoint blockade (ICB) strategies alone or in combination with tumor-targeting treatments …

Pca-Clf: A Classifier Of Prostate Cancer Patients Into Patients With Indolent And Aggressive Tumors Using Machine Learning, Yashwanth Karthik Kumar Mamidi, Tarun Karthik Kumar Mamidi, Md Wasi Ul Kabir, Jiande Wu, Md Tamjidul Hoque, Chindo Hicks

School of Medicine Faculty Publications

A critical unmet medical need in prostate cancer (PCa) clinical management centers around distinguishing indolent from aggressive tumors. Traditionally, Gleason grading has been utilized for this purpose. However, tumor classification using Gleason Grade 7 is often ambiguous, as the clinical behavior of these tumors follows a variable clinical course. This study aimed to investigate the application of machine learning techniques (ML) to classify patients into indolent and aggressive PCas. We used gene expression data from The Cancer Genome Atlas and compared gene expression levels between indolent and aggressive tumors to identify features for developing and validating a range of ML …

Her3 Targeting Augments The Efficacy Of Panobinostat In Claudin-Low Triple-Negative Breast Cancer Cells, Hui Lyu, Defu Hou, Hao Liu, Sanbao Ruan, Congcong Tan, Jiande Wu, Chindo Hicks, Bolin Liu

School of Medicine Faculty Publications

Patients with triple-negative breast cancer (TNBC) have a poor prognosis and high relapse rate due to limited therapeutic options. This study was conducted to determine the mechanisms of action of panobinostat, a pan-inhibitor of histone deacetylase (HDAC) and FDA-approved medication for multiple myeloma, in TNBC and to provide a rationale for effective drug combinations against this aggressive disease. RNA sequencing analyses of the claudin-low (CL) TNBC (MDA-MB-231) cells untreated or treated with panobinostat were performed to identify the differentially expressed genes. Adaptive alterations in gene expression were analyzed and validated in additional CL TNBC cells. Tumor xenograft models were used …

Targeting Glutaminase Is Therapeutically Effective In Ibrutinib-Resistant Mantle Cell Lymphoma, Lingzhi Li, Lei Nie, Alexa Jordan, Qingsong Cai, Yang Liu, Yijing Li, Yuxuan Che, Jovanny Vargas, Zhihong Chen, Angela Leeming, Wei Wang, Yixin Yao, Michael Wang, Vivian Changying Jiang

Faculty, Staff and Student Publications

Mantle cell lymphoma (MCL) is an incurable B-cell non-Hodgkin lymphoma characterized by frequent relapses. The development of resistance to ibrutinib therapy remains a major challenge in MCL. We previously showed that glutaminolysis is associated with resistance to ibrutinib. In this study, we confirmed that glutaminase (GLS), the first enzyme in glutaminolysis, is overexpressed in ibrutinib-resistant MCL cells, and that its expression correlates well with elevated glutamine dependency and glutaminolysis. Furthermore, we discovered that GLS expression correlates with MYC expression and the functioning of the glutamine transporter ASCT2. Depletion of glutamine or GLS significantly reduced cell growth, while GLS overexpression enhanced …

Using Cancer Proteomics Data To Identify Gene Candidates For Therapeutic Targeting, Diana Monsivais, Sydney E Parks, Darshan S Chandrashekar, Sooryanarayana Varambally, Chad J Creighton

Faculty, Staff and Students Publications

Gene-level associations obtained from mass-spectrometry-based cancer proteomics datasets represent a resource for identifying gene candidates for functional studies. When recently surveying proteomic correlates of tumor grade across multiple cancer types, we identified specific protein kinases having a functional impact on uterine endometrial cancer cells. This previously published study provides just one template for utilizing public molecular datasets to discover potential novel therapeutic targets and approaches for cancer patients. Proteomic profiling data combined with corresponding multi-omics data on human tumors and cell lines can be analyzed in various ways to prioritize genes of interest for interrogating biology. Across hundreds of cancer …

A Distinct Pattern Of Growth And Rac1 Signaling In Melanoma Brain Metastasis Cells, Ioana Stejerean-Todoran, Phyllis A Gimotty, Andrea Watters, Patricia Brafford, Clemens Krepler, Tetiana Godok, Haiyin Li, Zuriñe Bonilla Del Rio, Anke Zieseniss, Dörthe M Katschinski, Sinem M Sertel, Silvio O Rizzoli, Bradley Garman, Katherine L Nathanson, Xiaowei Xu, Qing Chen, Jack H Oswald, Michal Lotem, Gordon B Mills, Michael A Davies, Michael P Schön, Ivan Bogeski, Meenhard Herlyn, Adina Vultur

Faculty, Staff and Student Publications

Background: Melanoma, the deadliest of skin cancers, has a high propensity to form brain metastases that are associated with a markedly worsened prognosis. In spite of recent therapeutic advances, melanoma brain lesions remain a clinical challenge, biomarkers predicting brain dissemination are not clear and differences with other metastatic sites are poorly understood.

Methods: We examined a genetically diverse panel of human-derived melanoma brain metastasis (MBM) and extracranial cell lines using targeted sequencing, a Reverse Phase Protein Array, protein expression analyses, and functional studies in vitro and in vivo.

Results: Brain-specific genetic alterations were not detected; however, MBM cells in vitro …

Myo1e Overexpression In Lung Adenocarcinoma Is Associated With Increased Risk Of Mortality, Ignacio Jusue-Torres, Richies Tiv, Julio C. Ricarte-Filho, Apurva Mallisetty, Leglys Contreras-Vargas, Maria Jose Godoy-Calderon, Karam Khaddour, Kathleen Kennedy, Klara Valyi-Nagy, Odile David, Martha Menchaca, Anastasia Kottorou, Angelos Koutras, Foteinos Dimitrakopoulos, Khaled M. Abdelhady, Malek Massad, Israel Rubinstein, Lawrence Feldman, John Stewart, Takeshi Shimamura, Ludmila Danilova, Alicia Hulbert

School of Medicine Faculty Publications

This study aims to perform a comprehensive genomic analysis to assess the influence of overexpression of MYO1E in non-small cell lung carcinoma (NSCLC) and whether there are differences in survival and mortality risk in NSCLC patients depending on both DNA methylation and RNA expression of MYO1E. The DNA methylation probe cg13887966 was inversely correlated with MYO1E RNA expression in both LUAD and LUSC subpopulations showing that lower MYO1E RNA expression was associated with higher MYO1E DNA methylation. Late stages of lung cancer showed significantly lower MYO1E DNA methylation and significantly higher MYO1E RNA expression for LUAD but not for LUSC. …

Interactions Of Snps In Folate Metabolism Related Genes On Prostate Cancer Aggressiveness In European Americans And African Americans, Hui Yi Lin, Susan E. Steck, Indrani Sarkar, Elizabeth T.H. Fontham, Alan Diekman, Lora J. Rogers, Calvin T. Ratliff, Jeannette T. Bensen, James L. Mohler, L. Joseph Su

School of Public Health Faculty Publications

Background: Studies showed that folate and related single nucleotide polymorphisms (SNPs) could predict prostate cancer (PCa) risk. However, little is known about the interactions of folate-related SNPs associated with PCa aggressiveness. The study’s objective is to evaluate SNP–SNP interactions among the DHFR 19-bp polymorphism and 10 SNPs in folate metabolism and the one-carbon metabolism pathway associated with PCa aggressiveness. Methods: We evaluated 1294 PCa patients, including 690 European Americans (EAs) and 604 African Americans (AAs). Both individual SNP effects and pairwise SNP–SNP interactions were analyzed. Results: None of the 11 individual polymorphisms were significant for EAs and AAs. Three SNP–SNP …

Inhibition Of Ribosome Assembly Factor Pno1 By Crispr/Cas9 Technique Suppresses Lung Adenocarcinoma And Notch Pathway: Clinical Application, Sanjit K. Roy, Shivam Srivastava, Andrew Hancock, Anju Shrivastava, Jason Morvant, Sharmila Shankar, Rakesh K. Srivastava

School of Medicine Faculty Publications

Growth is crucially controlled by the functional ribosomes available in cells. To meet the enhanced energy demand, cancer cells re-wire and increase their ribosome biogenesis. The RNA-binding protein PNO1, a ribosome assembly factor, plays an essential role in ribosome biogenesis. The purpose of this study was to examine whether PNO1 can be used as a biomarker for lung adenocarcinoma and also examine the molecular mechanisms by which PNO1 knockdown by CRISPR/Cas9 inhibited growth and epithelial–mesenchymal transition (EMT). The expression of PNO1 was significantly higher in lung adenocarcinoma compared to normal lung tissues. PNO1 expression in lung adenocarcinoma patients increased with …