Digital Commons Network^™

Tp53 Gain-Of-Function Mutation Modulates The Immunosuppressive Microenvironment In Non-Hpv-Associated Oral Squamous Cell Carcinoma, Yewen Shi, Xiaoyong Ren, Shaolong Cao, Xi Chen, Bo Yuan, Fabio Henrique Brasil Da Costa, Alanis E Rodriguez Rosario, Arnoldo Corona, Chieko Michikawa, Ratna Veeramachaneni, Abdullah A Osman, Tongxin Xie, Wenyi Wang, Andrew G Sikora, Jeffrey N Myers, Roberto Rangel

Faculty, Staff and Student Publications

BACKGROUND: TP53, the most mutated gene in solid cancers, has a profound impact on most hallmarks of cancer. Somatic TP53 mutations occur in high frequencies in head and neck cancers, including oral squamous cell carcinoma (OSCC). Our study aims to understand the role of TP53 gain-of-function mutation in modulating the tumor immune microenvironment (TIME) in OSCC.

METHODS: Short hairpin RNA knockdown of mutant p53R172H in syngeneic oral tumors demonstrated changes in tumor growth between immunocompetent and immunodeficient mice. HTG EdgeSeq targeted messenger RNA sequencing was used to analyze cytokine and immune cell markers in tumors with inactivated mutant p53R172H …

Role Of Circulating Mitochondria In Venous Thrombosis In Glioblastoma, Ricardo Gonzalez-Delgado, Nina M Muñoz, Wendolyn Carlos-Alcalde, Min Soon Cho, Hani Lee, Jeff Jin, Victoria Serpas, Olga Gorlova, Rahul A Sheth, Vahid Afshar-Kharghan

Faculty, Staff and Student Publications

Background: Many patients with glioblastoma multiforme (GBM) develop deep venous thrombosis or pulmonary emboli. Cell-free circulating mitochondria increase after brain injury and are associated with coagulopathy.

Objectives: This study evaluated whether mitochondria play a role in the GBM-induced hypercoagulable state.

Methods: We examined the correlation between cell-free circulating mitochondria and venous thrombosis in patients with GBM and the impact of mitochondria on venous thrombosis in mice with inferior vena cava stenosis.

Results: Using plasma samples of 82 patients with GBM, we found that patients with GBM had a higher number of mitochondria in their plasma (GBM with venous thromboembolism [VTE],: …

Outcomes Of Young Adults (Aged ≤ 40 Years) With Newly Diagnosed Multiple Myeloma After Up-Front Autologous Stem Cell Transplant, Oren Pasvolsky, Curtis Marcoux, Denái R Milton, Mark R Tanner, Qaiser Bashir, Samer Srour, Neeraj Saini, Paul Lin, Jeremy Ramdial, Yago Nieto, Hans C Lee, Krina K Patel, Partow Kebriaei, Priti Tewari, Lindsay Crawford-Suber, Sheeba K Thomas, Donna M Weber, Robert Z Orlowski, Elizabeth J Shpall, Richard E Champlin, Muzaffar H Qazilbash

Faculty, Staff and Student Publications

Multiple myeloma (MM) primarily affects older patients. There are scarce data on the outcomes of young adults undergoing autologous transplantation (auto-HCT). In this single-centre analysis, we included 117 younger patients, with a median age of 37 years (range 22-40) at transplant. Seventeen (15%) patients had high-risk cytogenetics. Before transplant, 10% of patients achieved ≥CR and 44% achieved ≥VGPR. At best post-transplant response, 56% and 77% of patients achieved ≥CR and ≥VGPR respectively. With a median follow-up for survivors of 72.6 months (range 0.9-238.0), median PFS and OS were 43.1 months (95% CI 31.2-65.0) and 146.6 months (95% CI 100.0-208.1) respectively. …

A Review Of A Strategic Roadmapping Exercise To Advance Clinical Translation Of Photoacoustic Imaging: From Current Barriers To Future Adoption, Hisham Assi, Rui Cao, Madhura Castelino, Ben Cox, Fiona J Gilbert, Janek Gröhl, Kurinchi Gurusamy, Lina Hacker, Aoife M Ivory, James Joseph, Ferdinand Knieling, Martin J Leahy, Ledia Lilaj, Srirang Manohar, Igor Meglinski, Carmel Moran, Andrea Murray, Alexander A Oraevsky, Mark D Pagel, Manojit Pramanik, Jason Raymond, Mithun Kuniyil Ajith Singh, William C Vogt, Lihong Wang, Shufan Yang, Members Of Ipasc, Sarah E Bohndiek

Faculty, Staff and Student Publications

Photoacoustic imaging (PAI), also referred to as optoacoustic imaging, has shown promise in early-stage clinical trials in a range of applications from inflammatory diseases to cancer. While the first PAI systems have recently received regulatory approvals, successful adoption of PAI technology into healthcare systems for clinical decision making must still overcome a range of barriers, from education and training to data acquisition and interpretation. The International Photoacoustic Standardisation Consortium (IPASC) undertook an community exercise in 2022 to identify and understand these barriers, then develop a roadmap of strategic plans to address them. Here, we outline the nature and scope of …

Analysis Of Genomic And Immune Intratumor Heterogeneity In Linitis Plastica Via Multiregional Exome And T-Cell Receptor Sequencing, Jin Huang, Guofeng Zhao, Qiu Peng, Xin Yi, Liyan Ji, Jing Li, Pansong Li, Yanfang Guan, Jie Ge, Ling Chen, Runzhe Chen, Xin Hu, Won-Chul Lee, Alexandre Reuben, P Andrew Futreal, Xuefeng Xia, Jian Ma, Jianjun Zhang, Zihua Chen

Faculty, Staff and Student Publications

The molecular landscape and the intratumor heterogeneity (ITH) architecture of gastric linitis plastica (LP) are poorly understood. We performed whole-exome sequencing (WES) and T-cell receptor (TCR) sequencing on 40 tumor regions from four LP patients. The landscape and ITH at the genomic and immunological levels in LP tumors were compared with multiple cancers that have previously been reported. The lymphocyte infiltration was further assessed by immunohistochemistry (IHC) in LP tumors. In total, we identified 6339 non-silent mutations from multi-samples, with a median tumor mutation burden (TMB) of 3.30 mutations per Mb, comparable to gastric adenocarcinoma from the Cancer Genome Atlas …

Brief Report: Clinical Response, Toxicity, And Resistance Mechanisms To Osimertinib Plus Met Inhibitors In Patients With Egfr-Mutant Met-Amplified Nsclc, Kaiwen Wang, Robyn Du, Sinchita Roy-Chowdhuri, Ziping T Li, Lingzhi Hong, Natalie Vokes, Yasir Y Elamin, Celyne Bueno Hume, Ferdinandos Skoulidis, Carl M Gay, George Blumenschein, Frank V Fossella, Anne Tsao, Jianjun Zhang, Niki Karachaliou, Aurora O'Brate, Claudia-Nanette Gann, Jeff Lewis, Waree Rinsurongkawong, J Jack Lee, Don Lynn Gibbons, Ara A Vaporciyan, John V Heymach, Mehmet Altan, Xiuning Le

Faculty, Staff and Student Publications

INTRODUCTION:MET amplification is a known resistance mechanism to EGFR tyrosine kinase inhibitor (TKI) treatment in EGFR-mutant NSCLC. Dual EGFR-MET inhibition has been reported with success in overcoming such resistance and inducing clinical benefit. Resistance mechanisms to dual EGFR-MET inhibition require further investigation and characterization.

METHODS: Patients with NSCLC with both MET amplification and EGFR mutation who have received crizotinib, capmatinib, savolitinib, or tepotinib plus osimertinib (OSI) after progression on OSI at MD Anderson Cancer Center were included in this study. Molecular profiling was completed by means of fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS). Radiological response …

Risk Of Cancer After Diagnosis Of Cardiovascular Disease, Caitlin F Bell, Xiudong Lei, Allen Haas, Richard A Baylis, Hua Gao, Lingfeng Luo, Sharon H Giordano, Mackenzie R Wehner, Kevin T Nead, Nicholas J Leeper

Faculty, Staff and Student Publications

BACKGROUND: Cardiovascular disease (CVD) and cancer share several risk factors. Although preclinical models show that various types of CVD can accelerate cancer progression, clinical studies have not determined the impact of atherosclerosis on cancer risk.

OBJECTIVES: The objective of this study was to determine whether CVD, especially atherosclerotic CVD, is independently associated with incident cancer.

METHODS: Using IBM MarketScan claims data from over 130 million individuals, 27 million cancer-free subjects with a minimum of 36 months of follow-up data were identified. Individuals were stratified by presence or absence of CVD, time-varying analysis with multivariable adjustment for cardiovascular risk factors was …

Tmbim6 Deficiency Leads To Bone Loss By Accelerating Osteoclastogenesis, Sun-Ju Yi, You-Jee Jang, Seokchan Lee, Sung-Jin Cho, Kyuho Kang, Jae-Il Park, Han-Jung Chae, Hyung-Ryong Kim, Kyunghwan Kim

Faculty, Staff and Student Publications

TMBIM6 is an endoplasmic reticulum (ER) protein that modulates various physiological and pathological processes, including metabolism and cancer. However, its involvement in bone remodeling has not been investigated. In this study, we demonstrate that TMBIM6 serves as a crucial negative regulator of osteoclast differentiation, a process essential for bone remodeling. Our investigation of Tmbim6-knockout mice revealed an osteoporotic phenotype, and knockdown of Tmbim6 inhibited the formation of multinucleated tartrate-resistant acid phosphatase-positive cells, which are characteristic of osteoclasts. Transcriptome and immunoblot analyses uncovered that TMBIM6 exerts its inhibitory effect on osteoclastogenesis by scavenging reactive oxygen species and preventing p65 nuclear localization. …

Association Of Patient-Reported Health-Related Quality Of Life With Physician-Reported Toxicities In Adolescents And Young Adults Receiving Radiation Therapy For Cancer, Kelsey L Corrigan, Bryce B Reeve, John M Salsman, Elizabeth J Siembida, Grace L Smith, Maria C Swartz, Kamaria L Lee, Faraz Afridi, Lauren M Andring, Andrew J Bishop, Jillian R Gunther, J Andrew Livingston, Susan K Peterson, Susan K Parsons, Michael Roth

Faculty, Staff and Student Publications

PURPOSE: Radiation therapy (RT) may cause toxicities in adolescents and young adults (AYAs, age 15-39 years) with cancer. However, the range of RT-related toxicities in AYAs and the affect on health-related quality of life (HRQOL) has not been well studied. We performed a cross-sectional study in AYAs with cancer who received RT to identify RT-related toxicities and examine their impact on HRQOL.

MATERIALS AND METHODS: A total of 178 AYAs received RT and completed PROMIS HRQOL instruments from 2018 to 2022. Acute and late physician-graded Common Terminology Criteria for Adverse Events RT-related toxicities were extracted and described. Multivariable linear regression …

Prame And Lef1 In Combined Deep Penetrating Nevus And Combined Blue Nevus: Utility And Pitfall, Kaitlin Vanderbeck, Aimi T Rothrock, Woo Cheal Cho, Priyadharsini Nagarajan, Phyu P Aung, Courtney Hudgens, Roland L Bassett, Doina Ivan, Victor G Prieto, Jonathan L Curry, Carlos A Torres-Cabala

Faculty, Staff and Student Publications

Deep penetrating nevi (DPN), particularly those showing combined features, or combined deep penetrating nevi (CDPN), may show histopathological resemblance to blue nevus (BN) and melanoma. Preferentially Expressed Antigen in MElanoma (PRAME) is a marker that helps distinguish melanoma from benign melanocytic lesions. Lymphoid enhancer-binding factor 1 (LEF1) has been proposed to be used in conjunction with β-catenin for diagnosis of DPN. The immunohistochemical expression of PRAME and LEF1 was evaluated in 10 DPN (including 6 CDPN and 2 DPN-like proliferations with atypical features), 16 BN (including combined and cellular BN), and 2 melanomas with features of DPN or BN. PRAME …

The Initial Age-Associated Decline In Early T-Cell Progenitors Reflects Fewer Pre-Thymic Progenitors And Altered Signals In The Bone Marrow And Thymus Microenvironments, Jayashree Srinivasan, Anusha Vasudev, Carolyn Shasha, Hilary J Selden, Encarnacion Perez, Bonnie Lafleur, Shripad A Sinari, Andreas Krueger, Ellen R Richie, Lauren I R Ehrlich

Faculty, Staff and Student Publications

Age-related thymus involution results in decreased T-cell production, contributing to increased susceptibility to pathogens and reduced vaccine responsiveness. Elucidating mechanisms underlying thymus involution will inform strategies to restore thymopoiesis with age. The thymus is colonized by circulating bone marrow (BM)-derived thymus seeding progenitors (TSPs) that differentiate into early T-cell progenitors (ETPs). We find that ETP cellularity declines as early as 3 months (3MO) of age in mice. This initial ETP reduction could reflect changes in thymic stromal niches and/or pre-thymic progenitors. Using a multicongenic progenitor transfer approach, we demonstrate that the number of functional TSP/ETP niches does not diminish with …

Definitive Liver Radiotherapy For Intrahepatic Cholangiocarcinoma With Extrahepatic Metastases, Brian De, Rituraj Upadhyay, Kaiping Liao, Tiffany Kumala, Christopher Shi, Grace Dodoo, Joseph Abi Jaoude, Kelsey L Corrigan, Gohar S Manzar, Kathryn E Marqueen, Vincent Bernard, Sunyoung S Lee, Kanwal P S Raghav, Jean-Nicolas Vauthey, Ching-Wei D Tzeng, Hop S Tran Cao, Grace Lee, Jennifer Y Wo, Theodore S Hong, Christopher H Crane, Bruce D Minsky, Grace L Smith, Emma B Holliday, Cullen M Taniguchi, Albert C Koong, Prajnan Das, Milind Javle, Ethan B Ludmir, Eugene J Koay

Faculty, Staff and Student Publications

INTRODUCTION: Tumor-related liver failure (TRLF) is the most common cause of death in patients with intrahepatic cholangiocarcinoma (ICC). Though we previously showed that liver radiotherapy (L-RT) for locally advanced ICC is associated with less frequent TRLF and longer overall survival (OS), the role of L-RT for patients with extrahepatic metastatic disease (M1) remains undefined. We sought to compare outcomes for M1 ICC patients treated with and without L-RT.

METHODS: We reviewed ICC patients that found to have M1 disease at initial diagnosis at a single institution between 2010 and 2021 who received L-RT, matching them with an institutional cohort by …

Smooth Muscle Α-Actin Missense Variant Promotes Atherosclerosis Through Modulation Of Intracellular Cholesterol In Smooth Muscle Cells, Kaveeta Kaw, Abhijnan Chattopadhyay, Pujun Guan, Jiyuan Chen, Suravi Majumder, Xue-Yan Duan, Shuangtao Ma, Chen Zhang, Callie S Kwartler, Dianna M Milewicz

Faculty, Staff and Student Publications

AIMS: The variant p.Arg149Cys in ACTA2, which encodes smooth muscle cell (SMC)-specific α-actin, predisposes to thoracic aortic disease and early onset coronary artery disease in individuals without cardiovascular risk factors. This study investigated how this variant drives increased atherosclerosis.

METHODS AND RESULTS: Apoe-/- mice with and without the variant were fed a high-fat diet for 12 weeks, followed by evaluation of atherosclerotic plaque formation and single-cell transcriptomics analysis. SMCs explanted from Acta2R149C/+ and wildtype (WT) ascending aortas were used to investigate atherosclerosis-associated SMC phenotypic modulation. Hyperlipidemic Acta2R149C/+Apoe-/- mice have a 2.5-fold increase in atherosclerotic plaque burden compared to Apoe-/- mice …

Assessing Cocaine Motivational Value: Comparison Of Brain Reactivity Bias Toward Cocaine Cues And Cocaine Demand, Heather E Webber, Jin H Yoon, Constanza De Dios, Robert Suchting, Vincent Dang, Francesco Versace, Charles E Green, Margaret C Wardle, Scott D Lane, Joy M Schmitz

Faculty, Staff and Student Publications

The behavioral economic measure drug demand and the neural measure late positive potential (LPP) are two measures of motivational value that have been associated with drug relapse risk and treatment outcomes. Despite having overlapping themes, no studies have directly compared drug demand and LPP. Participants (N = 59) included treatment-seeking individuals with cocaine use disorder that had completed both a baseline cocaine demand task and an electroencephalogram (EEG) picture-viewing task of drug-related and pleasant picture cues. Associations between the LPP difference score amplitude (drug-pleasant) and five demand indices (Q₀, essential value [EV], Omax, Pmax, and …

Heterozygous Midnolin Knockout Attenuates Severity Of Nonalcoholic Fatty Liver Disease In Mice Fed A Western-Style Diet High In Fat, Cholesterol, And Fructose, Soo-Mi Kweon, Jose Irimia-Dominguez, Gayeoun Kim, Patrick T Fueger, Kinji Asahina, Keith K Lai, Daniela S Allende, Quincy R Lai, Chih-Hong Lou, Walter M Tsark, Ju Dong Yang, Dominic S Ng, Ju-Seog Lee, Patrick Tso, Wendong Huang, Keane K Y Lai

Faculty, Staff and Student Publications

Although midnolin has been studied for over 20 years, its biological roles in vivo remain largely unknown, especially due to the lack of a functional animal model. Indeed, given our recent discovery that the knockdown of midnolin suppresses liver cancer cell tumorigenicity and that this antitumorigenic effect is associated with modulation of lipid metabolism, we hypothesized that knockout of midnolin in vivo could potentially protect from nonalcoholic fatty liver disease (NAFLD) which has become the most common cause of chronic liver disease in the Western world. Accordingly, in the present study, we have developed and now report on the first …

Lipid Droplet Biogenesis And Functions In Health And Disease, Armella Zadoorian, Ximing Du, Hongyuan Yang

Faculty, Staff and Student Publications

Ubiquitous yet unique, lipid droplets are intracellular organelles that are increasingly being recognized for their versatility beyond energy storage. Advances uncovering the intricacies of their biogenesis and the diversity of their physiological and pathological roles have yielded new insights into lipid droplet biology. Despite these insights, the mechanisms governing the biogenesis and functions of lipid droplets remain incompletely understood. Moreover, the causal relationship between the biogenesis and function of lipid droplets and human diseases is poorly resolved. Here, we provide an update on the current understanding of the biogenesis and functions of lipid droplets in health and disease, highlighting a …

Vincristine Enhances The Efficacy Of Mek Inhibitors In Preclinical Models Of Kras-Mutant Colorectal Cancer, Susmita Ghosh, Fan Fan, Reid T Powell, Jason Roszik, Yong Sung Park, Clifford Stephan, Manu Sebastian, Lin Tan, Alexey V Sorokin, Philip L Lorenzi, Scott Kopetz, Lee M Ellis, Rajat Bhattacharya

Faculty, Staff and Student Publications

Mutations in KRAS are found in more than 50% of tumors from patients with metastatic colorectal cancer (mCRC). However, direct targeting of most KRAS mutations is difficult; even the recently developed KRASG12C inhibitors failed to show significant benefit in patients with mCRC. Single agents targeting mitogen-activated protein kinase kinase (MEK), a downstream mediator of RAS, have also been ineffective in colorectal cancer. To identify drugs that can enhance the efficacy of MEK inhibitors, we performed unbiased high-throughput screening using colorectal cancer spheroids. We used trametinib as the anchor drug and examined combinations of trametinib with the NCI-approved Oncology Library version …

Zeb1 Is Regulated By K811 Acetylation To Promote Stability, Nurd Complex Interactions, Emt, And Nsclc Metastasis, Mabel Perez-Oquendo, Roxsan Manshouri, Yanhua Tian, Jared J Fradette, B Leticia Rodriguez, Samrat T Kundu, Don L Gibbons

Faculty, Staff and Student Publications

Epithelial-to-mesenchymal transition results in loss of specialized epithelial cell contacts and acquisition of mesenchymal invasive capacity. The transcription repressor zinc finger E-box-binding homeobox 1 (ZEB1) binds to E-boxes of gene promoter regions to suppress the expression of epithelial genes. ZEB1 has inconsistent molecular weights, which have been attributed to posttranslational modifications (PTM). We performed mass spectrometry and identified K811 acetylation as a novel PTM in ZEB1. To define the role of ZEB1 acetylation in regulating function, we generated ZEB1 acetyl-mimetic (K811Q) and acetyl-deficient (K811R) mutant-expressing non-small cell lung cancer cell lines (NSCLC). We demonstrate that the K811R ZEB1 (125 kDa) …

Myelodysplastic Syndromes: 2023 Update On Diagnosis, Risk-Stratification, And Management, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

Disease overview: The myelodysplastic syndromes (MDS) are a very heterogeneous group of myeloid disorders characterized by peripheral blood cytopenias and increased risk of transformation to acute myelogenous leukemia (AML). MDS occurs more frequently in older males and in individuals with prior exposure to cytotoxic therapy.

Diagnosis: Diagnosis of MDS is based on morphological evidence of dysplasia upon visual examination of a bone marrow aspirate and biopsy. Information obtained from additional studies such as karyotype, flow cytometry, and molecular genetics is usually complementary and may help refine diagnosis. A new WHO classification of MDS was proposed in 2022. Under this classification, …

Cell-Type-Specific Prediction Of 3d Chromatin Organization Enables High-Throughput In Silico Genetic Screening, Jimin Tan, Nina Shenker-Tauris, Javier Rodriguez-Hernaez, Eric Wang, Theodore Sakellaropoulos, Francesco Boccalatte, Palaniraja Thandapani, Jane Skok, Iannis Aifantis, David Fenyö, Bo Xia, Aristotelis Tsirigos

Faculty, Staff and Student Publications

Investigating how chromatin organization determines cell-type-specific gene expression remains challenging. Experimental methods for measuring three-dimensional chromatin organization, such as Hi-C, are costly and have technical limitations, restricting their broad application particularly in high-throughput genetic perturbations. We present C.Origami, a multimodal deep neural network that performs de novo prediction of cell-type-specific chromatin organization using DNA sequence and two cell-type-specific genomic features-CTCF binding and chromatin accessibility. C.Origami enables in silico experiments to examine the impact of genetic changes on chromatin interactions. We further developed an in silico genetic screening approach to assess how individual DNA elements may contribute to chromatin organization and …

Diverse Clonal Fates Emerge Upon Drug Treatment Of Homogeneous Cancer Cells, Yogesh Goyal, Gianna T Busch, Maalavika Pillai, Jingxin Li, Ryan H Boe, Emanuelle I Grody, Manoj Chelvanambi, Ian P Dardani, Benjamin Emert, Nicholas Bodkin, Jonas Braun, Dylan Fingerman, Amanpreet Kaur, Naveen Jain, Pavithran T Ravindran, Ian A Mellis, Karun Kiani, Gretchen M Alicea, Mitchell E Fane, Syeda Subia Ahmed, Haiyin Li, Yeqing Chen, Cedric Chai, Jessica Kaster, Russell G Witt, Rossana Lazcano, Davis R Ingram, Sarah B Johnson, Khalida Wani, Margaret C Dunagin, Alexander J Lazar, Ashani T Weeraratna, Jennifer A Wargo, Meenhard Herlyn, Arjun Raj

Faculty, Staff and Student Publications

Even among genetically identical cancer cells, resistance to therapy frequently emerges from a small subset of those cells1-7. Molecular differences in rare individual cells in the initial population enable certain cells to become resistant to therapy7-9; however, comparatively little is known about the variability in the resistance outcomes. Here we develop and apply FateMap, a framework that combines DNA barcoding with single-cell RNA sequencing, to reveal the fates of hundreds of thousands of clones exposed to anti-cancer therapies. We show that resistant clones emerging from single-cell-derived cancer cells adopt molecularly, morphologically and …

Radiotherapy Use And Incidence Of Locoregional Recurrence In Patients With Favorable-Risk, Node-Positive Breast Cancer Enrolled In The Swog S1007 Trial, Reshma Jagsi, William E Barlow, Wendy A Woodward, Eileen Connolly, Reshma Mahtani, Dean Shumway, Corey Speers, Shane R Stecklein, Youssef Zeidan, Hong Zhang, Priyanka Sharma, Lajos Pusztai, Gabriel N Hortobagyi, Kevin Kalinsky

Faculty, Staff and Student Publications

IMPORTANCE: Little is known about regional nodal irradiation (RNI) practice patterns or rates of locoregional recurrence (LRR) with and without RNI in patients with limited nodal disease and favorable biology treated with modern surgical and systemic therapy, including approaches that de-escalate those latter treatments.

OBJECTIVE: To investigate how often patients with low-recurrence score breast cancer with 1 to 3 nodes involved receive RNI, incidence and predictors of LRR, and associations between locoregional therapy and disease-free survival.

DESIGN, SETTING, AND PARTICIPANTS: In this secondary analysis of the SWOG S1007 trial, patients with hormone receptor-positive, ERBB2-negative breast cancer, and a Oncotype DX …

Clinical, Endoscopic, And Histopathologic Gastrointestinal Disease In An American Cohort With Behçet's Disease, Bryan F Curtin, Kareen L Hill, Sumona Bhattacharya, Astin Powers, Aradhana Venkatesan, Preet Bagi, Elizabeth Joyal, Meghna Alimchandani, Raphaela Goldbach-Mansky, Peter Grayson, Martha Quezado, Cailin Sibley, Theo Heller

Faculty, Staff and Student Publications

INTRODUCTION: Behçet's disease (BD) is a chronic systemic vasculitis characterized by oral and genital ulcers, uveitis, and skin lesions. Patients with BD may develop gastrointestinal (GI) disease; however, characterization of GI disease in American cohorts is lacking. In this article, we present clinical, endoscopic, and histopathologic GI findings in an American cohort of patients with BD.

METHODS: Patients with established BD were evaluated prospectively at the National Institutes of Health. Demographic and clinical data were collected including BD manifestations and GI symptoms. Endoscopy with histopathologic sampling was performed for both clinical and research indications with written consent.

RESULTS: Eighty-three patients …

Blastoid And Pleomorphic Mantle Cell Lymphoma Demonstrate Distinct Clinicopathologic And Genetic Features, Mahsa Khanlari, Huan Mo, Do Hwan Kim, Ali Sakhdari, Ken H Young, Preetesh Jain, Michael Wang, Shaoying Li, Rashmi Kanagal-Shamanna, Roberto N Miranda, Francisco Vega, L Jeffrey Medeiros, Chi Young Ok

Faculty, Staff and Student Publications

The blastoid (B) and pleomorphic (P) variants of mantle cell lymphoma (MCL) are associated with aggressive clinical behavior. In this study, we collected 102 cases of B-MCL and P-MCL from untreated patients. We reviewed clinical data, analyzed morphologic features using an image analysis tool (ImageJ) and we assessed mutational and gene expression profiles. The chromatin pattern of lymphoma cells was assessed quantitatively by the pixel value. Cases of B-MCL showed a greater median pixel value with lower variation compared with P-MCL, indicating a homogeneously euchromatin-rich pattern in B-MCL. In addition, the Feret diameter of the nuclei was significantly smaller (median …

Prospective Evaluation Of In Vivo And Phantom Repeatability And Reproducibility Of Diffusion-Weighted Mri Sequences On 15 T Mri-Linear Accelerator (Mr-Linac) And Mr Simulator Devices For Head And Neck Cancers, Brigid A Mcdonald, Travis Salzillo, Samuel Mulder, Sara Ahmed, Alex Dresner, Kathryn Preston, Renjie He, John Christodouleas, Abdallah S R Mohamed, Marielle Philippens, Petra Van Houdt, Daniela Thorwarth, Jihong Wang, Amita Shukla Dave, Michael Boss, Clifton D Fuller

Faculty, Staff and Student Publications

INTRODUCTION: Diffusion-weighted imaging (DWI) on MRI-linear accelerator (MR-linac) systems can potentially be used for monitoring treatment response and adaptive radiotherapy in head and neck cancers (HNC) but requires extensive validation. We performed technical validation to compare six total DWI sequences on an MR-linac and MR simulator (MR sim) in patients, volunteers, and phantoms.

METHODS: Ten human papillomavirus-positive oropharyngeal cancer patients and ten healthy volunteers underwent DWI on a 1.5 T MR-linac with three DWI sequences: echo planar imaging (EPI), split acquisition of fast spin echo signals (SPLICE), and turbo spin echo (TSE). Volunteers were also imaged on a 1.5 T …

Multi-Parametric Mri For Radiotherapy Simulation, Tian Li, Jihong Wang, Yingli Yang, Carri K Glide-Hurst, Ning Wen, Jing Cai

Faculty, Staff and Student Publications

Magnetic resonance imaging (MRI) has become an important imaging modality in the field of radiotherapy (RT) in the past decade, especially with the development of various novel MRI and image-guidance techniques. In this review article, we will describe recent developments and discuss the applications of multi-parametric MRI (mpMRI) in RT simulation. In this review, mpMRI refers to a general and loose definition which includes various multi-contrast MRI techniques. Specifically, we will focus on the implementation, challenges, and future directions of mpMRI techniques for RT simulation.

Dynamics And Steering Of A Vibration-Driven Bristle Bot In A Pipe System, Ian Stewart

All Theses

Soft vibrational robots are robots that incorporate compliant structures into their design and are driven by oscillating actuators. A recent, popular version of a soft vibrational robot is the bristle bot, which uses flexible bristles and a vibration motor to propel itself across surfaces and through pipes. This motion is primarily driven by stick-slip dynamics resulting from asymmetric frictional forces applied at the bristle tips. Depending on the frequency of vibration of the motor, the robot experiences various resonance regions allowing it to maneuver in different directions. Attaching bristles to all sides of the robot and placing it in a …

Photodynamic Therapy To Treat Triple Negative Breast Cancer In Vitro, Hunter S. Warren

All Theses

Triple negative breast cancer (TNBC) is the most resilient form of breast cancer, being one of the leading causes of death for women and making up 7% of all cancer deaths. Photodynamic therapy (PDT) offers a minimally invasive solution to TNBC as a passive-targeting treatment that reduces the need for other well established yet harsh treatments that can be taxing on the patient. PDT involves the use of a high-energy red light on the area of a tumor injected with photosensitizers (PS) that generate reactive oxygen species (ROS) in the tumor, triggering cell death. The PS tetra(hydroxyphenyl)chlorin (m-THPC) was used …

"Things Can Get Unsavory": Professional Interactions, Social Capital, Organizational Identification Among University Resident Assistants, Michael L. Tidwell

All Theses

University resident assistants (RAs) have become a central component of modern higher education and community-oriented residential student experiences. RAs are increasingly responsible for not only community development and engagement of residential students, but also administrative and disciplinarian responsibilities (Boone et al., 2016; Conn, 2020). As a result, RAs face increased feelings of burnout (DuBose, 2020; Stoner, 2017), which research connects to higher turnover intentions and lower job satisfaction (Stoner, 2016, 2017). While most literature on RAs focuses on identification with various social groups (e.g., race, gender, sexuality), organizational identification (OI) – a deep-rooted sense of connection with an organization’s goals …

Multiplex Gene Editing In Hepatocytes As A Therapeutic Approach For Familial Hypercholesterolemia, Sarah Minich

All Theses

Familial hypercholesterolemia (FH) is a genetic disorder associated with elevated levels of low-density lipoprotein cholesterol (LDL-C) that increases the risk of atherosclerotic cardiovascular disease. FH affects 1 in 250 people.¹ Most FH cases are caused by loss-of-function mutations in the either one or both copies of the LDLR gene, which encodes for the LDL-C receptor protein and is responsible for removing excess LDL from the circulating blood plasma.² Current treatments for FH include medications that reduce LDL from the bloodstream.

Angiopoietin-like 3 (ANGPTL3) is a lipoprotein lipase inhibitor. Studies show that loss-of-function mutations in ANGPTL3 are associated with …