Medicine and Health Sciences Commons^™

Sensitivity Enhancement Of An Experimental Benchtop X-Ray Fluorescence Imaging System By Deploying A Single Crystal Cadmium Telluride Detector System Optimized For High Flux X-Ray Operations, Hem Moktan, Sandun Jayarathna, Sang Hyun Cho

Faculty, Staff and Student Publications

In this work, an energy-resolving thermoelectrically cooled single crystal cadmium telluride (CdTe) detector system upgraded with the latest firmware was optimized for high x-ray flux operations using high bias voltage and fast peaking time. This detector system was deployed into an experimental benchtop x-ray fluorescence (XRF) imaging/computed tomography (XFCT) system developed for quantitative imaging of metal nanoprobes such as gold nanoparticles (GNPs). Using the firmware-upgraded and existing/old CdTe detector systems, the Compton/XRF spectra from small (8 mm diameter) GNP-containing phantoms were acquired. The phantoms were irradiated with 1.8 mm Sn-filtered 125 kVp cone beam x-rays at 24 mA. The firmware-upgraded …

Effective Therapy For Aml With Runx1 Mutation By Cotreatment With Inhibitors Of Protein Translation And Bcl2, Christopher P Mill, Warren Fiskus, Courtney D Dinardo, Christine Birdwell, John A Davis, Tapan M Kadia, Koichi Takahashi, Nicholas Short, Naval Daver, Maro Ohanian, Gautam Borthakur, Steven M Kornblau, Michael R Green, Yuan Qi, Xiaoping Su, Joseph D Khoury, Kapil N Bhalla

Faculty, Staff and Student Publications

The majority of RUNX1 mutations in acute myeloid leukemia (AML) are missense or deletion-truncation and behave as loss-of-function mutations. Following standard therapy, AML patients expressing mtRUNX1 exhibit inferior clinical outcome than those without mutant RUNX1. Studies presented here demonstrate that as compared with AML cells lacking mtRUNX1, their isogenic counterparts harboring mtRUNX1 display impaired ribosomal biogenesis and differentiation, as well as exhibit reduced levels of wild-type RUNX1, PU.1, and c-Myc. Compared with AML cells with only wild-type RUNX1, AML cells expressing mtRUNX1 were also more sensitive to the protein translation inhibitor homoharringtonine (omacetaxine) and BCL2 inhibitor venetoclax. Homoharringtonine treatment repressed …

Lipid-Loaded Tumor-Associated Macrophages Sustain Tumor Growth And Invasiveness In Prostate Cancer, Michela Masetti, Roberta Carriero, Federica Portale, Giulia Marelli, Nicolò Morina, Marta Pandini, Marta Iovino, Bianca Partini, Marco Erreni, Andrea Ponzetta, Elena Magrini, Piergiuseppe Colombo, Grazia Elefante, Federico Simone Colombo, Joke M M Den Haan, Clelia Peano, Javier Cibella, Alberto Termanini, Paolo Kunderfranco, Jolanda Brummelman, Matthew Wai Heng Chung, Massimo Lazzeri, Rodolfo Hurle, Paolo Casale, Enrico Lugli, Ronald A Depinho, Subhankar Mukhopadhyay, Siamon Gordon, Diletta Di Mitri

Faculty, Staff and Student Publications

Tumor-associated macrophages (TAMs) are correlated with the progression of prostatic adenocarcinoma (PCa). The mechanistic basis of this correlation and therapeutic strategies to target TAMs in PCa remain poorly defined. Here, single-cell RNA sequencing was used to profile the transcriptional landscape of TAMs in human PCa, leading to identification of a subset of macrophages characterized by dysregulation in transcriptional pathways associated with lipid metabolism. This subset of TAMs correlates positively with PCa progression and shorter disease-free survival and is characterized by an accumulation of lipids that is dependent on Marco. Mechanistically, cancer cell-derived IL-1β enhances Marco expression on macrophages, and reciprocally, …

Home-Based Spirometry Telemonitoring After Allogeneic Hematopoietic Cell Transplantation: Mixed Methods Evaluation Of Acceptability And Usability, Ajay Sheshadri, Sukh Makhnoon, Amin M Alousi, Lara Bashoura, Rene Andrade, Christopher J Miller, Karen R Stolar, Muhammad Hasan Arain, Laila Noor, Amulya Balagani, Akash Jain, David Blanco, Abel Ortiz, Michael S Taylor, Alex Stenzler, Rohtesh Mehta, Uday R Popat, Chitra Hosing, David E Ost, Richard E Champlin, Burton F Dickey, Susan K Peterson

Faculty, Staff and Student Publications

Background: Home-based spirometry (HS) allows for the early detection of lung complications in recipients of an allogeneic hematopoietic cell transplant (AHCT). Although the usability and acceptability of HS are critical for adherence, patient-reported outcomes of HS use remain poorly understood in this setting.

Objective: The aim of this study is to design a longitudinal, mixed methods study to understand the usability and acceptability of HS among recipients of AHCT.

Methods: Study participants performed HS using a Bluetooth-capable spirometer that transmitted spirometry data to the study team in real time. In addition, participants completed usability questionnaires and in-depth interviews and reported …

Srgn-Triggered Aggressive And Immunosuppressive Phenotype In A Subset Of Ttf-1-Negative Lung Adenocarcinomas, Ichidai Tanaka, Delphine Dayde, Mei Chee Tai, Haruki Mori, Luisa M Solis, Satyendra C Tripathi, Johannes F Fahrmann, Nese Unver, Gargy Parhy, Rekha Jain, Edwin R Parra, Yoshiko Murakami, Clemente Aguilar-Bonavides, Barbara Mino, Muge Celiktas, Dilsher Dhillon, Julian Phillip Casabar, Masahiro Nakatochi, Francesco Stingo, Veera Baladandayuthapani, Hong Wang, Hiroyuki Katayama, Jennifer B Dennison, Philip L Lorenzi, Kim-Anh Do, Junya Fujimoto, Carmen Behrens, Edwin J Ostrin, Jaime Rodriguez-Canales, Tetsunari Hase, Takayuki Fukui, Taisuke Kajino, Seiichi Kato, Yasushi Yatabe, Waki Hosoda, Koji Kawaguchi, Kohei Yokoi, Toyofumi F Chen-Yoshikawa, Yoshinori Hasegawa, Adi F Gazdar, Ignacio I Wistuba, Samir Hanash, Ayumu Taguchi

Faculty, Staff and Student Publications

BACKGROUND: Approximately 20% of lung adenocarcinoma (LUAD) is negative for the lineage-specific oncogene Thyroid transcription factor 1 (TTF-1) and exhibits worse clinical outcome with a low frequency of actionable genomic alterations. To identify molecular features associated with TTF-1-negative LUAD, we compared the transcriptomic and proteomic profiles of LUAD cell lines. SRGN , a chondroitin sulfate proteoglycan Serglycin, was identified as a markedly overexpressed gene in TTF-1-negative LUAD. We therefore investigated the roles and regulation of SRGN in TTF-1-negative LUAD.

METHODS: Proteomic and metabolomic analyses of 41 LUAD cell lines were done using mass spectrometry. The function of SRGN was investigated …

The Online Ordering Behaviors Among Participants In The Oklahoma Women, Infants, And Children Program: A Cross-Sectional Analysis, Qi Zhang, Kayoung Park, Junzhou Zhang, Chuanyi Tang

Department of Marketing Faculty Scholarship and Creative Works

The Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) is a nutrition assistance program in the United States (U.S.). Participants in the program redeem their prescribed food benefits in WIC-authorized grocery stores. Online ordering is an innovative method being pilot-tested in some stores to facilitate WIC participants’ food benefit redemption, which has become especially important in the COVID-19 pandemic. The present research aimed to examine the online ordering (OO) behaviors among 726 WIC households who adopted WIC OO in a grocery chain, XYZ (anonymous) store, in Oklahoma (OK). These households represented approximately 5% of WIC households who redeemed …

Performance Determinants Of Unsupervised Clustering Methods For Microbiome Data, Yushu Shi, Liangliang Zhang, Christine B Peterson, Kim-Anh Do, Robert R Jenq

Faculty, Staff and Student Publications

Background: In microbiome data analysis, unsupervised clustering is often used to identify naturally occurring clusters, which can then be assessed for associations with characteristics of interest. In this work, we systematically compared beta diversity and clustering methods commonly used in microbiome analyses. We applied these to four published datasets where highly distinct microbiome profiles could be seen between sample groups, as well a clinical dataset with less clear separation between groups.

Results: Although no single method outperformed the others consistently, we did identify the key scenarios where certain methods can underperform. Specifically, the Bray Curtis (BC) metric resulted in poor …

Multiple Approaches Converge On Three Biological Subtypes Of Meningioma And Extract New Insights From Published Studies, James C Bayley, Caroline C Hadley, Arif O Harmanci, Akdes S Harmanci, Tiemo J Klisch, Akash J Patel

Faculty, Staff and Student Publications

One-fifth of meningiomas classified as benign by World Health Organization (WHO) histopathological grading will behave malignantly. To better diagnose these tumors, several groups turned to DNA methylation, whereas we combined RNA-sequencing (RNA-seq) and cytogenetics. Both approaches were more accurate than histopathology in identifying aggressive tumors, but whether they revealed similar tumor types was unclear. We therefore performed unbiased DNA methylation, RNA-seq, and cytogenetic profiling on 110 primary meningiomas WHO grade I and II). Each technique distinguished the same three groups (two benign and one malignant) as our previous molecular classification; integrating these methods into one classifier further improved accuracy. Computational …

Interplay Between Soluble Cd74 And Macrophage-Migration Inhibitory Factor Drives Tumor Growth And Influences Patient Survival In Melanoma, Yasunari Fukuda, Matias A Bustos, Sung-Nam Cho, Jason Roszik, Suyeon Ryu, Victor M Lopez, Jared K Burks, Jeffrey E Lee, Elizabeth A Grimm, Dave S B Hoon, Suhendan Ekmekcioglu

Faculty, Staff and Student Publications

Soluble forms of receptors play distinctive roles in modulating signal-transduction pathways. Soluble CD74 (sCD74) has been identified in sera of inflammatory diseases and implicated in their pathophysiology; however, few relevant data are available in the context of cancer. Here we assessed the composition and production mechanisms, as well as the clinical significance and biological properties, of sCD74 in melanoma. Serum sCD74 levels were significantly elevated in advanced melanoma patients compared with normal healthy donors, and the high ratio of sCD74 to macrophage-migration inhibitory factor (MIF) conferred significant predictive value for prolonged survival in these patients (p = 0.0035). Secretion of …

Verticox: Vertically Distributed Cox Proportional Hazards Model Using The Alternating Direction Method Of Multipliers, Wenrui Dai, Xiaoqian Jiang, Luca Bonomi, Yong Li, Hongkai Xiong, Lucila Ohno-Machado

Faculty, Staff and Student Publications

The Cox proportional hazards model is a popular semi-parametric model for survival analysis. In this paper, we aim at developing a federated algorithm for the Cox proportional hazards model over vertically partitioned data (i.e., data from the same patient are stored at different institutions). We propose a novel algorithm, namely VERTICOX, to obtain the global model parameters in a distributed fashion based on the Alternating Direction Method of Multipliers (ADMM) framework. The proposed model computes intermediary statistics and exchanges them to calculate the global model without collecting individual patient-level data. We demonstrate that our algorithm achieves equivalent accuracy for the …

Examining Rural-Urban Differences In Fatalism And Information Overload: Data From 12 Nci-Designated Cancer Centers, Jakob D Jensen, Jackilen Shannon, Ronaldo Iachan, Yangyang Deng, Sunny Jung Kim, Wendy Demark-Wahnefried, Babalola Faseru, Electra D Paskett, Jinxiang Hu, Robin C Vanderpool, Deann Lazovich, Jason A Mendoza, Sanjay Shete, Linda B Robertson, Rajesh Balkrishnan, Katherine J Briant, Benjamin Haaland, David A Haggstrom, Bernard F Fuemmeler, Rural Workgroup Of The Population Health Assessment In Cancer Center Catchment Areas Consortium

Faculty, Staff and Student Publications

BACKGROUND: Rural populations experience a disproportionate cancer burden relative to urban populations. One possibility is that rural populations are more likely to hold counterproductive cancer beliefs such as fatalism and information overload that undermine prevention and screening behaviors.

METHODS: Between 2016 and 2020, 12 U.S. cancer centers surveyed adults in their service areas using online and in-person survey instruments. Participants (

RESULTS: Compared with urban residents, rural residents were more likely to believe that (i) everything causes cancer (OR = 1.29; 95% CI, 1.17-1.43); (ii) prevention is not possible (OR = 1.34; 95% CI, 1.19-1.51); and (iii) there are too …

Breast Radiation Therapy-Related Treatment Outcomes In Patients With Or Without Germline Mutations On Multigene Panel Testing, Bhavana V Chapman, Diane Liu, Yu Shen, Oluwafikayo O Olamigoke, David S Lakomy, Angelica M Gutierrez Barrera, Shane R Stecklein, Gabriel O Sawakuchi, Scott J Bright, Isabelle Bedrosian, Jennifer K Litton, Benjamin D Smith, Wendy A Woodward, George H Perkins, Karen E Hoffman, Michael C Stauder, Eric A Strom, Banu K Arun, Simona F Shaitelman

Faculty, Staff and Student Publications

PURPOSE: Multigene panel testing has increased the detection of germline mutations in patients with breast cancer. The implications of using radiation therapy (RT) to treat patients with pathogenic variant (PV) mutations are not well understood and have been studied mostly in women with only BRCA1 or BRCA2 PVs. We analyzed oncologic outcomes and toxicity after adjuvant RT in a contemporary, diverse cohort of patients with breast cancer who underwent genetic panel testing.

METHODS AND MATERIALS: We retrospectively reviewed the records of 286 women with clinical stage I-III breast cancer diagnosed from 1995 to 2017 who underwent surgery, breast or chest …

Construction And Validation Of Prognostic Nomogram For Metaplastic Breast Cancer, Yongfeng Li, Daobao Chen, Haojun Xuan, Mihnea P Dragomir, George A Calin, Xuli Meng, Meng Chen, Hongchuan Jin

Faculty, Staff and Student Publications

In this study we aimed to develop nomogram models for predicting the overall survival (OS) and cancer-specific survival (CSS) of patients with metaplastic breast cancer (MBC). Data of patients diagnosed with MBC from 1973 to 2015 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox analyses were performed to identify independent prognostic factors for OS and CSS of MBC patients. The obtained prognostic variables were combined to construct nomogram models for predicting OS and CSS in patients with MBC. Model performance was evaluated using concordance index (C-index) and calibration plots. Data from 1125 patients …

Combined Il-2, Agonistic Cd3 And 4–1bb Stimulation Preserve Clonotype Hierarchy In Propagated Non-Small Cell Lung Cancer Tumor-Infiltrating Lymphocytes, Parin Shah, Marie-Andrée Forget, Meredith L Frank, Peixin Jiang, Donastas Sakellariou-Thompson, Lorenzo Federico, Roohussaba Khairullah, Chantal Alexia Neutzler, Ignacio Wistuba, Chi-Wan B Chow, Yan Long, Junya Fujimoto, Shiaw-Yih Lin, Anirban Maitra, Marcelo V Negrao, Kyle Gregory Mitchell, Annikka Weissferdt, Ara A Vaporciyan, Tina Cascone, Jack A Roth, Jianjun Zhang, Boris Sepesi, Don L Gibbons, John V Heymach, Cara L Haymaker, Daniel J Mcgrail, Alexandre Reuben, Chantale Bernatchez

Faculty, Staff and Student Publications

Background: Adoptive cell transfer (ACT) of tumor-infiltrating lymphocytes (TIL) yielded clinical benefit in patients with checkpoint blockade immunotherapy-refractory non-small cell lung cancer (NSCLC) prompting a renewed interest in TIL-ACT. This preclinical study explores the feasibility of producing a NSCLC TIL product with sufficient numbers and enhanced attributes using an improved culture method.

Methods: TIL from resected NSCLC tumors were initially cultured using (1) the traditional method using interleukin (IL)-2 alone in 24-well plates (TIL 1.0) or (2) IL-2 in combination with agonistic antibodies against CD3 and 4-1BB (Urelumab) in a G-Rex flask (TIL 3.0). TIL subsequently underwent a rapid expansion …

Evaluation Of Programmed Death Ligand 1 Expression In Cytology To Determine Eligibility For Immune Checkpoint Inhibitor Therapy In Patients With Head And Neck Squamous Cell Carcinoma, Zhonghua Liu, Michelle Williams, John Stewart, Bonnie S Glisson, Clifton Fuller, Sinchita Roy-Chowdhuri

Faculty, Staff and Student Publications

Background: Immune checkpoint inhibitors targeting the programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway have recently emerged as a frontline treatment for head and neck squamous cell carcinoma (HNSCC). The evaluation of PD-L1 expression by immunohistochemistry in histologic samples is used to determine the eligibility of patients with HNSCC for immunotherapy. Patients with newly diagnosed HNSCC are frequently diagnosed by fine-needle aspiration (FNA) of lymph nodes with metastatic disease. However, the evaluation of PD-L1 expression with the proposed combined positive score (CPS) has not been well established in cytology specimens.

Methods: This study retrospectively identified 21 …

Corticosteroid-Refractory Myositis After Dual Braf And Mek Inhibition In A Patient With Braf V600e-Mutant Metastatic Intrahepatic Cholangiocarcinoma, Timothy P Diperi, Mehmet Demirhan, Daniel D Karp, Siqing Fu, David S Hong, Vivek Subbiah, Joann Lim, Leomar Y Ballester, Jean H Tayar, Maria E Suarez-Almazor, Milind Javle, Funda Meric-Bernstam

Faculty, Staff and Student Publications

Intrahepatic cholangiocarcinoma is a rare malignancy, which is rich in actionable alterations. Genomic aberrations in the mitogen-activated protein kinase (MAPK) pathway are common, and

Body Region-Specific 3d Age-Scaling Functions For Scaling Whole-Body Computed Tomography Anatomy For Pediatric Late Effects Studies, Aashish C Gupta, Constance A Owens, Suman Shrestha, Choonsik Lee, Susan A Smith, Rita E Weathers, Tucker Netherton, Peter A Balter, Stephen F Kry, David S Followill, Keith T Griffin, James P Long, Gregory T Armstrong, Rebecca M Howell

Faculty, Staff and Student Publications

Purpose:

Radiation epidemiology studies of childhood cancer survivors treated in the pre-computed tomography (CT) era reconstruct the patients’ treatment fields on computational phantoms. For such studies, the phantoms are commonly scaled to age at the time of radiotherapy treatment because age is the generally available anthropometric parameter. Several reference size phantoms are used in such studies, but reference size phantoms are only available at discrete ages (e.g.: newborn, 1, 5, 10, 15, and Adult). When such phantoms are used for RT dose reconstructions, the nearest discrete-aged phantom is selected to represent a survivor of a specific age. In this work, …

A Mechanistic Modeling Framework Reveals The Key Principles Underlying Tumor Metabolism, Shubham Tripathi, Jun Hyoung Park, Shivanand Pudakalakatti, Pratip K Bhattacharya, Benny Abraham Kaipparettu, Herbert Levine

Faculty, Staff and Student Publications

While aerobic glycolysis, or the Warburg effect, has for a long time been considered a hallmark of tumor metabolism, recent studies have revealed a far more complex picture. Tumor cells exhibit widespread metabolic heterogeneity, not only in their presentation of the Warburg effect but also in the nutrients and the metabolic pathways they are dependent on. Moreover, tumor cells can switch between different metabolic phenotypes in response to environmental cues and therapeutic interventions. A framework to analyze the observed metabolic heterogeneity and plasticity is, however, lacking. Using a mechanistic model that includes the key metabolic pathways active in tumor cells, …

Clinical And Molecular Characterization Of Pole Mutations As Predictive Biomarkers Of Response To Immune Checkpoint Inhibitors In Advanced Cancers, Benjamin Garmezy, Jinesh Gheeya, Heather Y Lin, Yuefan Huang, Taebeom Kim, Xianli Jiang, Kyaw Z Thein, Patrick G Pilié, Fadl Zeineddine, Wanlin Wang, Kenna R Shaw, Jordi Rodon, John Paul Shen, Ying Yuan, Funda Meric-Bernstam, Ken Chen, Timothy A Yap

Faculty, Staff and Student Publications

Purpose: DNA polymerase epsilon is critical to DNA proofreading and replication. Mutations in POLE have been associated with hypermutated tumors and antitumor response to immune checkpoint inhibitor (ICI) therapy. We present a clinicopathologic analysis of patients with advanced cancers harboring POLE mutations, the pattern of co-occurring mutations, and their response to ICI therapy within the context of mutation pathogenicity.

Methods: We conducted a retrospective analysis of next-generation sequencing data at MD Anderson Cancer Center to identify patient tumors with POLE mutations and their co-occurring mutations. The pathogenicity of each mutation was annotated using InterVar and ClinVar. Differences in therapeutic response …

Ces2 Sustains Hnf4Α Expression To Promote Pancreatic Adenocarcinoma Progression Through An Epoxide Hydrolase-Dependent Regulatory Loop, Yihui Chen, Michela Capello, Mayrim V Rios Perez, Jody V Vykoukal, David Roife, Ya'an Kang, Laura R Prakash, Hiroyuki Katayama, Ehsan Irajizad, Alia Fleury, Sammy Ferri-Borgogno, Dodge L Baluya, Jennifer B Dennison, Kim-Anh Do, Oliver Fiehn, Anirban Maitra, Huamin Wang, Paul J Chiao, Matthew H G Katz, Jason B Fleming, Samir M Hanash, Johannes F Fahrmann

Faculty, Staff and Student Publications

Objective: Intra-tumoral expression of the serine hydrolase carboxylesterase 2 (CES2) contributes to the activation of the pro-drug irinotecan in pancreatic ductal adenocarcinoma (PDAC). Given other potential roles of CES2, we assessed its regulation, downstream effects, and contribution to tumor development in PDAC.

Methods: Association between the mRNA expression of CES2 in pancreatic tumors and overall survival was assessed using The Cancer Genome Atlas. Cell viability, clonogenic, and anchorage-independent growth assays as well as an orthotopic mouse model of PDAC were used to evaluate the biological relevance of CES2 in pancreatic cancer. CES2-driven metabolic changes were determined by untargeted and targeted …

Effects Of Placebo Administration On Immune Mechanisms And Relationships With Central Endogenous Opioid Neurotransmission, Alan Prossin, Alisa Koch, Phillip Campbell, Geoffroy Laumet, Christian S Stohler, Robert Dantzer, Jon-Kar Zubieta

Faculty, Staff and Student Publications

Behavioral conditioning and expectation can have profound impact on animal and human physiology. Placebo, administered under positive expectation in clinical trials, can have potent effects on disease pathology, obscuring active medications. Emerging evidence suggests placebo-responsive neurotransmitter systems (e.g., endogenous opioid) regulate immune function by manipulating inflammatory proteins including IL-18, a potent pro-inflammatory, nociceptive cytokine implicated in pathophysiology of various diseases. Validation that neuroimmune interactions involving brain μ-opioid receptor (MOR) activity and plasma IL-18 underlie placebo analgesic expectation could have widespread clinical applications. Unfortunately, current lack of mechanistic clarity obfuscates clinical translation. To elucidate neuroimmune interactions underlying placebo analgesia, we exposed …

Final Results Of The Choroid Plexus Tumor Study Cpt-Siop-2000, Johannes E Wolff, Stefaan W Van Gool, Tezer Kutluk, Blanca Diez, Rejin Kebudi, Beate Timmermann, Miklos Garami, Jaroslav Sterba, Gregory N Fuller, Brigitte Bison, Uwe R Kordes

Faculty, Staff and Student Publications

INTRODUCTION: Standards for chemotherapy against choroid plexus tumors (CPT) have not yet been established.

METHODS: CPT-SIOP-2000 (NCT00500890) was an international registry for all CPT nesting a chemotherapy randomization for high-risk CPT with Carboplatin/Etoposide/Vincristine (CarbEV) versus Cyclophosphamide/Etoposide/Vincristine (CycEV). Patients older than three years were recommended to receive irradiation: focal fields for non-metastatic CPC, incompletely resected atypical choroid plexus papilloma (APP) or metastatic choroid plexus papilloma (CPP); craniospinal fields for metastatic CPC/APP and non-responsive CPC. High risk was defined as choroid plexus carcinoma (CPC), incompletely resected APP, and all metastatic CPT. From 2000 until 2010, 158 CPT patients from 23 countries were …

A Predictive Model For Geographical Location Using Microbiome Composition And Covid-19 Based Analysis, Ahmed Adel Aboushanab

Theses and Dissertations

The human microbiome is a main contributor for the health and welfare of the human body. It is affected by many factors like diet and hygiene. These factors differ between different populations. Testing the population-microbiome differences using healthy samples from different countries is the first objective of this study. This data was then used in training and testing machine learning models (Random Forest and L2-logistic Regression Classifiers) for the prediction of the geographical location based on the microbiome data. Random Forest Classifier had the highest accuracy. Feature importance analysis showed that the data for Proteobacteria, Actinobacteria, and Bacteroidetes improved the …

Identifying The Metabolic Signatures Of Ppard-Overexpressing Gastric Tumors, Shivanand Pudakalakatti, Mark Titus, José S Enriquez, Sumankalai Ramachandran, Niki M Zacharias, Imad Shureiqi, Yi Liu, James C Yao, Xiangsheng Zuo, Pratip K Bhattacharya

Faculty, Staff and Student Publications

Peroxisome proliferator-activated receptor delta (PPARD) is a nuclear receptor known to play an essential role in regulation of cell metabolism, cell proliferation, inflammation, and tumorigenesis in normal and cancer cells. Recently, we found that a newly generated villin-PPARD mouse model, in which PPARD is overexpressed in villin-positive gastric progenitor cells, demonstrated spontaneous development of large, invasive gastric tumors as the mice aged. However, the role of PPARD in regulation of downstream metabolism in normal gastric and tumor cells is elusive. The aim of the present study was to find PPARD-regulated downstream metabolic changes and to determine the potential significance of …

Gene-Gene Interaction Of Ahrwith And Within The Wntcascade Affects Susceptibility To Lung Cancer, Albert Rosenberger, Nils Muttray, Rayjean J Hung, David C Christiani, Neil E Caporaso, Geoffrey Liu, Stig E Bojesen, Loic Le Marchand, Demetrios Albanes, Melinda C Aldrich, Adonina Tardon, Guillermo Fernández-Tardón, Gad Rennert, John K Field, Michael P A Davies, Triantafillos Liloglou, Lambertus A Kiemeney, Philip Lazarus, Bernadette Wendel, Aage Haugen, Shanbeh Zienolddiny, Stephen Lam, Matthew B Schabath, Angeline S Andrew, Eric J Duell, Susanne M Arnold, Gary E Goodman, Chu Chen, Jennifer A Doherty, Fiona Taylor, Angela Cox, Penella J Woll, Angela Risch, Thomas R Muley, Mikael Johansson, Paul Brennan, Maria Teresa Landi, Sanjay S Shete, Christopher I Amos, Heike Bickeböller, Integral-Ilcco Consortium

Faculty, Staff and Student Publications

Background: Aberrant Wnt signalling, regulating cell development and stemness, influences the development of many cancer types. The Aryl hydrocarbon receptor (AhR) mediates tumorigenesis of environmental pollutants. Complex interaction patterns of genes assigned to AhR/Wnt-signalling were recently associated with lung cancer susceptibility.

Aim: To assess the association and predictive ability of AhR/Wnt-genes with lung cancer in cases and controls of European descent.

Methods: Odds ratios (OR) were estimated for genomic variants assigned to the Wnt agonist and the antagonistic genes DKK2, DKK3, DKK4, FRZB, SFRP4 and Axin2. Logistic regression models with variable selection were trained, validated and tested to predict lung …

Impact Of Frontline Treatment Approach On Outcomes In Patients With Secondary Aml With Prior Hypomethylating Agent Exposure, Nicholas J Short, Sangeetha Venugopal, Wei Qiao, Tapan M Kadia, Farhad Ravandi, Walid Macaron, Courtney D Dinardo, Naval Daver, Marina Konopleva, Gautam Borthakur, Elizabeth J Shpall, Uday Popat, Richard E Champlin, Rohtesh Mehta, Gheath Al-Atrash, Betul Oran, Elias Jabbour, Guillermo Garcia-Manero, Ghayas C Issa, Guillermo Montalban-Bravo, Musa Yilmaz, Abhishek Maiti, Hagop Kantarjian

Faculty, Staff and Student Publications

BACKGROUND: Treated secondary acute myeloid leukemia (ts-AML)-i.e., AML arising from a previously treated antecedent hematologic disorder-is associated with very poor outcomes. The optimal frontline treatment regimen for these patients is uncertain.

METHODS: We retrospectively analyzed 562 patients who developed AML from preceding myelodysplastic syndrome or chronic myelomonocytic leukemia for which they had received a hypomethylating agent (HMA). Patients with ts-AML were stratified by frontline AML treatment with intensive chemotherapy (IC, n = 271), low-intensity therapy (LIT) without venetoclax (n = 237), or HMA plus venetoclax (n = 54).

RESULTS: Compared with IC or LIT without venetoclax, HMA plus venetoclax resulted …

Transcribed Ultraconserved Regions Are Associated With Clinicopathological Features In Breast Cancer, Erika Pereira Zambalde, Douglas Adamoski, Daniela Fiori Gradia, Iris Rabinovich, Ana Carolina Rodrigues, Cristina Ivan, Enilze M S F Ribeiro, George Adrian Calin, Jaqueline Carvalho De Oliveira

Faculty, Staff and Student Publications

Ultraconserved regions (UCRs) are 481 genome segments, with length longer than 200 bp, that are 100% conserved among humans, mice, and rats. The majority of UCRs are transcriptionally active (T-UCRs) as many of them produce non-coding RNAs. In a previous study, we evaluated the expression level of T-UCRs in breast cancer (BC) patients and found that 63% of transcripts correlated with some clinical and/or molecular parameter of BC. In this study, we delved into the expression levels of 12 T-UCRs and correlated them with clinicopathological parameters, immunohistochemical markers, and overall survival in two breast cancer cohorts: TCGA and Brazilian patients. …

Machine Learning For Predicting Risk Of Early Dropout In A Recovery Program For Opioid Use Disorder, Assaf Gottlieb, Andrea Yatsco, Christine Bakos-Block, James R Langabeer, Tiffany Champagne-Langabeer

Faculty, Staff and Student Publications

BACKGROUND: An increase in opioid use has led to an opioid crisis during the last decade, leading to declarations of a public health emergency. In response to this call, the Houston Emergency Opioid Engagement System (HEROES) was established and created an emergency access pathway into long-term recovery for individuals with an opioid use disorder. A major contributor to the success of the program is retention of the enrolled individuals in the program.

METHODS: We have identified an increase in dropout from the program after 90 and 120 days. Based on more than 700 program participants, we developed a machine learning …

Systematic Decomposition Of Sequence Determinants Governing Crispr/Cas9 Specificity, Rongjie Fu, Wei He, Jinzhuang Dou, Oscar D Villarreal, Ella Bedford, Helen Wang, Connie Hou, Liang Zhang, Yalong Wang, Dacheng Ma, Yiwen Chen, Xue Gao, Martin Depken, Han Xu

Faculty, Staff and Student Publications

The specificity of CRISPR/Cas9 genome editing is largely determined by the sequences of guide RNA (gRNA) and the targeted DNA, yet the sequence-dependent rules underlying off-target effects are not fully understood. To systematically explore the sequence determinants governing CRISPR/Cas9 specificity, here we describe a dual-target system to measure the relative cleavage rate between off- and on-target sequences (off-on ratios) of 1902 gRNAs on 13,314 synthetic target sequences, and reveal a set of sequence rules involving 2 factors in off-targeting: 1) a guide-intrinsic mismatch tolerance (GMT) independent of the mismatch context; 2) an "epistasis-like" combinatorial effect of multiple mismatches, which are …

Efficacy And Safety Of Enasidenib And Azacitidine Combination In Patients With Idh2 Mutated Acute Myeloid Leukemia And Not Eligible For Intensive Chemotherapy, Sangeetha Venugopal, Koichi Takahashi, Naval Daver, Abhishek Maiti, Gautam Borthakur, Sanam Loghavi, Nicholas J Short, Maro Ohanian, Lucia Masarova, Ghayas Issa, Xuemei Wang, Bueso-Ramos Carlos, Musa Yilmaz, Tapan Kadia, Michael Andreeff, Farhad Ravandi, Marina Konopleva, Hagop M Kantarjian, Courtney D Dinardo

Faculty, Staff and Student Publications

Preclinically, enasidenib and azacitidine (ENA + AZA) synergistically enhance cell differentiation, and venetoclax (VEN), a small molecule Bcl2 inhibitor (i) is particularly effective in IDH2 mutated acute myeloid leukemia (IDH2mutAML). This open label phase II trial enrolled patients (pts) with documented IDH2mutAML. All patients received AZA 75 mg/m2/d x 7 d/cycle and ENA 100 mg QD continuously. Concomitant Bcl2i and FLT3i were allowed (NCT03683433).Twenty-six pts received ENA + AZA (median 68 years, range, 24-88); 7 newly diagnosed (ND) and 19 relapsed/refractory (R/R). In R/R AML patients, three had received prior ENA and none had received prior VEN. The …