Medical Sciences Commons^™

Colorectal Surveillance Outcomes From An Institutional Longitudinal Cohort Of Lynch Syndrome Carriers, Gabriel Del Carmen, Laura Reyes-Uribe, Daniel Goyco, Kyera Evans, Charles M Bowen, Jennifer L Kinnison, Valerie O Sepeda, Diane M Weber, Julie Moskowitz, Maureen E Mork, Selvi Thirumurthi, Patrick M Lynch, Miguel A Rodriguez-Bigas, Melissa W Taggart, Y Nancy You, Eduardo Vilar

Faculty, Staff and Student Publications

OBJECTIVE: Lynch Syndrome (LS) carriers have a significantly increased risk of developing colorectal cancer (CRC) during their lifetimes. Further stratification of this patient population may help in identifying additional risk factors that predispose to colorectal carcinogenesis. In most LS patients CRC may arise from adenomas, although an alternative non-polypoid carcinogenesis pathway has been proposed for

DESIGN: We collected demographics, genetic, colonoscopy, and pathology results from a total of 163 LS carriers who obtained regular screening care at MD Anderson Cancer Center. Data were extracted from the electronic health records into a REDCap database for analysis. Logistic regressions were performed to …

Factors Associated With Nonsyndromic Anotia And Microtia, Texas, 1999–2014, Jeremy M Schraw, J P Woodhouse, Renata H Benjamin, Charles J Shumate, Joanne Nguyen, Mark A Canfield, A J Agopian, Philip J Lupo

Faculty, Staff and Students Publications

BACKGROUND: Few risk factors have been identified for nonsyndromic anotia/microtia (A/M).

METHODS: We obtained data on cases and a reference population of all livebirths in Texas for 1999-2014 from the Texas Birth Defects Registry (TBDR) and Texas vital records. We estimated prevalence ratios (PRs) and 95% confidence intervals (CIs) for A/M (any, isolated, nonisolated, unilateral, and bilateral) using Poisson regression. We evaluated trends in prevalence rates using Joinpoint regression.

RESULTS: We identified 1,322 cases, of whom 982 (74.3%) had isolated and 1,175 (88.9%) had unilateral A/M. Prevalence was increased among males (PR: 1.3, 95% CI: 1.2-1.4), offspring of women with …

Hras Mutations Define A Distinct Subgroup In Head And Neck Squamous Cell Carcinoma, Niamh Coleman, Kathrina L Marcelo, Julia F Hopkins, Nusrat Israr Khan, Robyn Du, Lingzhi Hong, Edward Park, Binaifer Balsara, Mollie Leoni, Curtis Pickering, Jeffrey Myers, John Heymach, Lee A Albacker, David Hong, Maura Gillison, Xiuning Le

Faculty, Staff and Student Publications

Purpose: In head and neck squamous cell carcinoma (HNSCC), HRAS mutation is a new actionable oncogene driver. We aimed to evaluate HRAS mutational variants, comutation profile, and survival outcomes of this molecularly defined population.

Methods: We leveraged four deidentified patient data sets with HRAS-mutant HNSCC, MD Anderson Cancer Center, Kura Oncology, Inc trial, Foundation Medicine, and American Association for Cancer Research GENIE v.12. Patient demographic information and clinical courses were extracted, when available, in addition to HRAS mutation type and co-occurring mutations. Survival outcomes were analyzed (Kaplan-Meier method).

Results: Two hundred forty-nine patients with HRAS-mutant HNSCC were identified …

Financial Toxicity In Cancer Patients And Subsequent Risk Of Repeat Acute Care Utilization, Julia J Shi, J Alberto Maldonado, Chi-Fang Wu, Susan K Peterson, Ying-Shiuan Chen, Kevin Diao, Robert J Volk, Sharon H Giordano, Ya-Chen T Shih, Kelsey Kaiser, Grace L Smith

Faculty, Staff and Student Publications

BACKGROUND: Acute care (AC) visits by cancer patients are costly sources of healthcare resources and can exert a financial burden of oncology care both for individuals with cancer and healthcare systems. We sought to identify whether cancer patients who reported more severe initial financial toxicity (FT) burdens shouldered excess risks for acute care utilization.

METHODS: In 225 adult patients who participated in the Economic Strain and Resilience in Cancer (ENRICh) survey study of individuals receiving ambulatory cancer care between March and September 2019, we measured the baseline FT (a multidimensional score of 0-10 indicating the least to most severe global, …

Pilot Study Of A Spanish Language Measure Of Financial Toxicity In Underserved Hispanic Cancer Patients With Low English Proficiency, Julia J Shi, Gwendolyn J Mcginnis, Susan K Peterson, Nicolette Taku, Ying-Shiuan Chen, Robert K Yu, Chi-Fang Wu, Tito R Mendoza, Sanjay S Shete, Hilary Ma, Robert J Volk, Sharon H Giordano, Ya-Chen T Shih, Diem-Khanh Nguyen, Kelsey W Kaiser, Grace L Smith

Faculty, Staff and Student Publications

BACKGROUND: Financial toxicity (FT) reflects multi-dimensional personal economic hardships borne by cancer patients. It is unknown whether measures of FT-to date derived largely from English-speakers-adequately capture economic experiences and financial hardships of medically underserved low English proficiency US Hispanic cancer patients. We piloted a Spanish language FT instrument in this population.

METHODS: We piloted a Spanish version of the Economic Strain and Resilience in Cancer (ENRICh) FT measure using qualitative cognitive interviews and surveys in un-/under-insured or medically underserved, low English proficiency, Spanish-speaking Hispanics (UN-Spanish,

RESULTS: UN-Spanish Hispanic participants reported high acceptability of the instrument (only 0% responded that the …

Self-Administered Meditation Application Intervention For Cancer Patients With Psychosocial Distress: A Pilot Study, Gabriel Lopez, Alejandro Chaoul, Carla L Warneke, Aimee J Christie, Catherine Powers-James, Wenli Liu, Santhosshi Narayanan, Marvin Delgado-Guay, Yisheng Li, Eduardo Bruera, Lorenzo Cohen

Faculty, Staff and Student Publications

BACKGROUND: We explored the use of a novel smart phone-based application (APP) for delivery and monitoring of meditation to treat mood symptoms experienced by cancer patients.

METHODS: We assessed the feasibility of using a meditation delivery and tracking APP over 2-weeks and its impact on cancer patients' self-reported anxiety and depression. Outpatients reporting depression and/or anxiety were recruited and randomized to the APP or waitlist control group. Assessments included an expectancy scale, exit survey, mood rating before and after each meditation, and the Edmonton Symptom Assessment Scale (ESAS-FS), Hospital Anxiety and Depression Scale (HADS), and Pittsburgh Sleep Quality Index (PSQI) …

Novornabreak: Local Assembly For Novel Splice Junction And Fusion Transcript Detection From Rna-Seq Data, Yukun Tan, Vakul Mohanty, Shaoheng Liang, Jinzhuang Dou, Jun Ma, Kun Hee Kim, Marc Jan Bonder, Xinghua Shi, Charles Lee, Zechen Chong, Ken Chen

Faculty, Staff and Student Publications

We present novoRNABreak, a unified framework for cancer specific novel splice junction and fusion transcript detection in RNA-seq data obtained from human cancer samples. novoRNABreak is based on a local assembly model, which offers a tradeoff between the alignment-based and de novo whole transcriptome assembly (WTA) methods. This approach is accurate and sensitive in assembling novel junctions that are difficult to directly align or have multiple alignments. Additionally, it is more efficient due to the strategy that focuses on junctions rather than full length transcripts. The performance of novoRNABreak is demonstrated by a comprehensive set of experiments using synthetic data …

Editorial: Prion-Like Transmission Of Pathogenic Proteins In Neurodegenerative Diseases: Structural And Molecular Bases, Victor Banerjee, Fei Wang, Daniela Sarnataro, Claudio Soto

Faculty, Staff and Student Publications

No abstract provided.

Easy Nanostring Ncounter Data Analysis With The Nanotube, Caleb A Class, Caiden J Lukan, Christopher A Bristow, Kim-Anh Do

Faculty, Staff and Student Publications

Summary: The NanoTube is an open-source pipeline that simplifies the processing, quality control, normalization and analysis of NanoString nCounter gene expression data. It is implemented in an extensible R library, which performs a variety of gene expression analysis techniques and contains additional functions for integration with other R libraries performing advanced NanoString analysis techniques. Additionally, the NanoTube web application is available as a simple tool for researchers without programming expertise.

Availability and implementation: The NanoTube R package is available on Bioconductor under the GPL-3 license (https://www.bioconductor.org/packages/NanoTube/). The R-Shiny application can be downloaded at https://github.com/calebclass/Shiny-NanoTube, or a simplified …

Targeting Immunosuppressive Ly6c+ Classical Monocytes Reverses Anti-Pd-1/Ctla-4 Immunotherapy Resistance, B Leticia Rodriguez, Limo Chen, Yanli Li, Shucheng Miao, David H Peng, Jared J Fradette, Lixia Diao, Jessica M Konen, Frank R Rojas Alvarez, Luisa M Solis, Xiaohui Yi, Aparna Padhye, Laura A Gibson, Joshua K Ochieng, Xiaofei Zhou, Jing Wang, Don L Gibbons

Faculty, Staff and Student Publications

Introduction: Despite significant clinical advancement with the use of immune checkpoint blockade (ICB) in non-small cell lung cancer (NSCLC) there are still a major subset of patients that develop adaptive/acquired resistance. Understanding resistance mechanisms to ICB is critical to developing new therapeutic strategies and improving patient survival. The dynamic nature of the tumor microenvironment and the mutational load driving tumor immunogenicity limit the efficacy to ICB. Recent studies indicate that myeloid cells are drivers of ICB resistance. In this study we sought to understand which immune cells were contributing to resistance and if we could modify them in a way …

Multi-Organ Spatial Stratification Of 3-D Dose Distributions Improves Risk Prediction Of Long-Term Self-Reported Severe Symptoms In Oropharyngeal Cancer Patients Receiving Radiotherapy: Development Of A Pre-Treatment Decision Support Tool, Andrew Wentzel, Abdallah S R Mohamed, Mohamed A Naser, Lisanne V Van Dijk, Katherine Hutcheson, Amy M Moreno, Clifton D Fuller, Guadalupe Canahuate, G Elisabeta Marai

Faculty, Staff and Student Publications

Purpose: Identify Oropharyngeal cancer (OPC) patients at high-risk of developing long-term severe radiation-associated symptoms using dose volume histograms for organs-at-risk, via unsupervised clustering.

Material and methods: All patients were treated using radiation therapy for OPC. Dose-volume histograms of organs-at-risk were extracted from patients' treatment plans. Symptom ratings were collected via the MD Anderson Symptom Inventory (MDASI) given weekly during, and 6 months post-treatment. Drymouth, trouble swallowing, mucus, and vocal dysfunction were selected for analysis in this study. Patient stratifications were obtained by applying Bayesian Mixture Models with three components to patient's dose histograms for relevant organs. The clusters with the …

Overview Of The Hecktor Challenge At Miccai 2022: Automatic Head And Neck Tumor Segmentation And Outcome Prediction In Pet/Ct, Vincent Andrearczyk, Valentin Oreiller, Moamen Abobakr, Azadeh Akhavanallaf, Panagiotis Balermpas, Sarah Boughdad, Leo Capriotti, Joel Castelli, Catherine Cheze Le Rest, Pierre Decazes, Ricardo Correia, Dina El-Habashy, Hesham Elhalawani, Clifton D Fuller, Mario Jreige, Yornna Khamis, Agustina La Greca, Abdallah Mohamed, Mohamed Naser, John O Prior, Su Ruan, Stephanie Tanadini-Lang, Olena Tankyevych, Yazdan Salimi, Martin Vallières, Pierre Vera, Dimitris Visvikis, Kareem Wahid, Habib Zaidi, Mathieu Hatt, Adrien Depeursinge

Faculty, Staff and Student Publications

This paper presents an overview of the third edition of the HEad and neCK TumOR segmentation and outcome prediction (HECKTOR) challenge, organized as a satellite event of the 25th International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI) 2022. The challenge comprises two tasks related to the automatic analysis of FDG-PET/CT images for patients with Head and Neck cancer (H&N), focusing on the oropharynx region. Task 1 is the fully automatic segmentation of H&N primary Gross Tumor Volume (GTVp) and metastatic lymph nodes (GTVn) from FDG-PET/CT images. Task 2 is the fully automatic prediction of Recurrence-Free Survival (RFS) …

Segmentation Stability Of Human Head And Neck Cancer Medical Images For Radiotherapy Applications Under De-Identification Conditions: Benchmarking Data Sharing And Artificial Intelligence Use-Cases, Jaakko Sahlsten, Kareem A Wahid, Enrico Glerean, Joel Jaskari, Mohamed A Naser, Renjie He, Benjamin H Kann, Antti Mäkitie, Clifton D Fuller, Kimmo Kaski

Faculty, Staff and Student Publications

BACKGROUND: Demand for head and neck cancer (HNC) radiotherapy data in algorithmic development has prompted increased image dataset sharing. Medical images must comply with data protection requirements so that re-use is enabled without disclosing patient identifiers. Defacing, i.e., the removal of facial features from images, is often considered a reasonable compromise between data protection and re-usability for neuroimaging data. While defacing tools have been developed by the neuroimaging community, their acceptability for radiotherapy applications have not been explored. Therefore, this study systematically investigated the impact of available defacing algorithms on HNC organs at risk (OARs).

METHODS: A publicly available dataset …

The Contemporary Management Of Cancers Of The Sinonasal Tract In Adults, Rajat Thawani, Myung Sun Kim, Asad Arastu, Zizhen Feng, Malinda T West, Nicholas F Taflin, Kyaw Zin Thein, Ryan Li, Mathew Geltzeiler, Nancy Lee, Clifton David Fuller, Jennifer R Grandis, Charalampos S Floudas, Michael C Heinrich, Ehab Hanna, Ravi A Chandra

Faculty, Staff and Student Publications

Sinonasal malignancies make up <5% of all head and neck neoplasms, with an incidence of 0.5-1.0 per 100,000. The outcome of these rare malignancies has been poor, whereas significant progress has been made in the management of other cancers. The objective of the current review was to describe the incidence, causes, presentation, diagnosis, treatment, and recent developments of malignancies of the sinonasal tract. The diagnoses covered in this review included sinonasal undifferentiated carcinoma, sinonasal adenocarcinoma, sinonasal squamous cell carcinoma, and esthesioneuroblastoma, which are exclusive to the sinonasal tract. In addition, the authors covered malignances that are likely to be encountered in the sinonasal tract-primary mucosal melanoma, NUT (nuclear protein of the testis) carcinoma, and extranodal natural killer cell/T-cell lymphoma. For the purpose of keeping this review as concise and focused as possible, sarcomas and malignancies that can be classified as salivary gland neoplasms were excluded.

Construction Of The Interaction Network Of Hub Genes In The Progression Of Barrett's Esophagus To Esophageal Adenocarcinoma, Kai Li, Peipei Duan, Haifa He, Ruijuan Du, Qian Wang, Pengju Gong, Hua Bian

Faculty, Staff and Student Publications

Introduction: Esophageal adenocarcinoma (EAC) is one of the histologic types of esophageal cancer with a poor prognosis. The majority of EAC originate from Barrett's esophagus (BE). There are few studies focusing on the dynamic progression of BE to EAC.

Methods: R software was used to analyze differentially expressed genes (DEGs) based on RNA-seq data of 94 normal esophageal squamous epithelial (NE) tissues, 113 BE tissues and 147 EAC tissues. The overlapping genes of DEGs between BE and EAC were analyzed by Venn diagram tool. The hub genes were selected by Cytoscape software based on the protein-protein interaction network of the …

Autologous T Cell Therapy For Mage-A4+ Solid Cancers In Hla-A*02+ Patients: A Phase 1 Trial, David S Hong, Brian A Van Tine, Swethajit Biswas, Cheryl Mcalpine, Melissa L Johnson, Anthony J Olszanski, Jeffrey M Clarke, Dejka Araujo, George R Blumenschein, Partow Kebriaei, Quan Lin, Alex J Tipping, Joseph P Sanderson, Ruoxi Wang, Trupti Trivedi, Thejo Annareddy, Jane Bai, Stavros Rafail, Amy Sun, Lilliam Fernandes, Jean-Marc Navenot, Frederic D Bushman, John K Everett, Derin Karadeniz, Robyn Broad, Martin Isabelle, Revashnee Naidoo, Natalie Bath, Gareth Betts, Zohar Wolchinsky, Dzmitry G Batrakou, Erin Van Winkle, Erica Elefant, Armin Ghobadi, Amanda Cashen, Anne Grand'maison, Philip Mccarthy, Paula M Fracasso, Elliot Norry, Dennis Williams, Mihaela Druta, David A Liebner, Kunle Odunsi, Marcus O Butler

Faculty, Staff and Student Publications

Affinity-optimized T cell receptors can enhance the potency of adoptive T cell therapy. Afamitresgene autoleucel (afami-cel) is a human leukocyte antigen-restricted autologous T cell therapy targeting melanoma-associated antigen A4 (MAGE-A4), a cancer/testis antigen expressed at varying levels in multiple solid tumors. We conducted a multicenter, dose-escalation, phase 1 trial in patients with relapsed/refractory metastatic solid tumors expressing MAGE-A4, including synovial sarcoma (SS), ovarian cancer and head and neck cancer ( NCT03132922 ). The primary endpoint was safety, and the secondary efficacy endpoints included overall response rate (ORR) and duration of response. All patients (N = 38, nine tumor types) experienced …

Risk Prediction Of Pancreatic Cancer In Patients With Recent-Onset Hyperglycemia: A Machine-Learning Approach, Wansu Chen, Rebecca K Butler, Eva Lustigova, Suresh T Chari, Anirban Maitra, Jo A Rinaudo, Bechien U Wu

Faculty, Staff and Student Publications

Background: New-onset diabetes (NOD) has been suggested as an early indicator of pancreatic cancer. However, the definition of NOD by the American Diabetes Association requires 2 simultaneous or consecutive elevated glycemic measures. We aimed to apply a machine-learning approach using electronic health records to predict the risk in patients with recent-onset hyperglycemia.

Materials and methods: In this retrospective cohort study, health plan enrollees 50 to 84 years of age who had an elevated (6.5%+) glycated hemoglobin (HbA1c) tested in January 2010 to September 2018 with recent-onset hyperglycemia were identified. A total of 102 potential predictors were extracted. Ten imputation datasets …

A Comparative Analysis Of Radical Cystectomy With Perioperative Chemotherapy, Chemoradiation Therapy, Or Systemic Therapy In Patients With Clinically Advanced Node-Positive Bladder Cancer (Cn2/N3), Harshit Garg, Mukund Bhandari, Furkan Dursun, Michael A Liss, Dharam Kaushik, Robert S Svatek, Ahmed M Mansour

Faculty, Staff and Student Publications

Introduction: The management of non-metastatic clinically advanced lymph nodal (cN2/N3) bladder cancer (Stage IIIB) could involve radical cystectomy, chemoradiation, or systemic therapy alone. However, a definitive comparison between these approaches is lacking. This study aims to compare the outcomes of patients undergoing radical cystectomy with pelvic lymph node dissection (RC-PLND), chemoradiation therapy (CRT) or systemic therapy (including immunotherapy) (ST) only in patients with stage IIIB bladder cancer.

Materials and methods: A retrospective analysis of the National Cancer Database for patients with stage IIIB urothelial bladder cancer was done from 2004-2019. Patients were classified as Group A: Those who received RC-PLND …

3,3′-Diindolylmethane Augments 5-Fluorouracil-Inducedgrowth Suppression In Gastric Cancer Cells Through Suppression Of The Akt/Gsk-3Β And Wnt/Beta-Catenin, Cong Shan Li, Thi Van Nguyen, Ok Hee Chai, Byung Hyun Park, Ju-Seog Lee, Soo Mi Kim

Faculty, Staff and Student Publications

Gastric cancer (GC) is one of the most lethal cancers in South Korea, and it is a cancer of concern worldwide. 5-fluorouracil (5-Fu) is commonly used as the first-line therapy for advanced GC; however, its side effects often limit the dosage range and impair patients' quality of life. Due to the limitations of current chemotherapy, new anticancer therapies are urgently needed. 3,3'-diindolylmethane (DIM) has been reported to have the ability to protect against various types of cancer. Our study aimed to elucidate the anticancer effect of DIM in GC when treated with the chemotherapeutic agent 5-Fu. In our results, combined …

Stellettin B Sensitizes Glioblastoma To Dna-Damaging Treatments By Suppressing Pi3k-Mediated Homologous Recombination Repair, Xin Peng, Shaolu Zhang, Yingying Wang, Zhicheng Zhou, Zixiang Yu, Zhenxing Zhong, Liang Zhang, Zhe-Sheng Chen, Francois X Claret, Moshe Elkabets, Feng Wang, Fan Sun, Ran Wang, Han Liang, Hou-Wen Lin, Dexin Kong

Faculty, Staff and Student Publications

Glioblastoma (GBM) is the most aggressive type of cancer. Its current first-line postsurgery regimens are radiotherapy and temozolomide (TMZ) chemotherapy, both of which are DNA damage-inducing therapies but show very limited efficacy and a high risk of resistance. There is an urgent need to develop novel agents to sensitize GBM to DNA-damaging treatments. Here it is found that the triterpene compound stellettin B (STELB) greatly enhances the sensitivity of GBM to ionizing radiation and TMZ in vitro and in vivo. Mechanistically, STELB inhibits the expression of homologous recombination repair (HR) factors BRCA1/2 and RAD51 by promoting the degradation of PI3Kα …

Bayesian Single-To-Double Arm Transition Design Using Both Short-Term And Long-Term Endpoints, Tianlin Xu, Haolun Shi, Ruitao Lin

Faculty, Staff and Student Publications

The choice between single-arm designs versus randomized double-arm designs has been contentiously debated in the literature of phase II oncology trials. Recently, as a compromise, the single-to-double arm transition design was proposed, combining the two designs into one trial over two stages. Successful implementation of the two-stage transition design requires a suspension period at the end of the first stage to collect the response data of the already enrolled patients. When the evaluation of the primary efficacy endpoint is overly long, the between-stage suspension period may unfavorably prolong the trial duration and cause a delay in treating future eligible patients. …

Evolutionary History Of Transformation From Chronic Lymphocytic Leukemia To Richter Syndrome, Erin M Parry, Ignaty Leshchiner, Romain Guièze, Connor Johnson, Eugen Tausch, Sameer A Parikh, Camilla Lemvigh, Julien Broséus, Sébastien Hergalant, Conor Messer, Filippo Utro, Chaya Levovitz, Kahn Rhrissorrakrai, Liang Li, Daniel Rosebrock, Shanye Yin, Stephanie Deng, Kara Slowik, Raquel Jacobs, Teddy Huang, Shuqiang Li, Geoff Fell, Robert Redd, Ziao Lin, Binyamin A Knisbacher, Dimitri Livitz, Christof Schneider, Neil Ruthen, Liudmila Elagina, Amaro Taylor-Weiner, Bria Persaud, Aina Martinez, Stacey M Fernandes, Noelia Purroy, Annabelle J Anandappa, Jialin Ma, Julian Hess, Laura Z Rassenti, Thomas J Kipps, Nitin Jain, William Wierda, Florence Cymbalista, Pierre Feugier, Neil E Kay, Kenneth J Livak, Brian P Danysh, Chip Stewart, Donna Neuberg, Matthew S Davids, Jennifer R Brown, Laxmi Parida, Stephan Stilgenbauer, Gad Getz, Catherine J Wu

Faculty, Staff and Student Publications

Richter syndrome (RS) arising from chronic lymphocytic leukemia (CLL) exemplifies an aggressive malignancy that develops from an indolent neoplasm. To decipher the genetics underlying this transformation, we computationally deconvoluted admixtures of CLL and RS cells from 52 patients with RS, evaluating paired CLL-RS whole-exome sequencing data. We discovered RS-specific somatic driver mutations (including IRF2BP2, SRSF1, B2M, DNMT3A and CCND3), recurrent copy-number alterations beyond del(9p21)(CDKN2A/B), whole-genome duplication and chromothripsis, which were confirmed in 45 independent RS cases and in an external set of RS whole genomes. Through unsupervised clustering, clonally related RS was largely distinct from diffuse large B cell lymphoma. …

Acute Myeloid Leukemia With Concurrent Npm1 And Runx1 Mutations, Zhuang Zuo, L Jeffrey Medeiros, C Cameron Yin

Faculty, Staff and Student Publications

NPM1 mutation, as a founding genetic event, cooperates with other gene mutations, such as DNMT3A and FLT3, to promote the development of acute myeloid leukemia. NPM1 mutation, however, has been reported to be mutually exclusive with RUNX1 mutation in acute myeloid leukemia cases. In this study, we analyzed mutation panel testing data from a relatively large cohort of rare AML cases with both NPM1 and RUNX1 mutations. We describe the dynamic process of the emergence of these mutations, as well as molecular genetic features and clinical outcome of these patients. We show that concurrence of both mutations in acute …

Revolutionizing Bone Regeneration: Advanced Biomaterials For Healing Compromised Bone Defects, Kamal Awad, Neelam Ahuja, Ahmed S Yacoub, Leticia Brotto, Simon Young, Antonios Mikos, Pranesh Aswath, Venu Varanasi

Faculty, Staff and Student Publications

In this review, we explore the application of novel biomaterial-based therapies specifically targeted towards craniofacial bone defects. The repair and regeneration of critical sized bone defects in the craniofacial region requires the use of bioactive materials to stabilize and expedite the healing process. However, the existing clinical approaches face challenges in effectively treating complex craniofacial bone defects, including issues such as oxidative stress, inflammation, and soft tissue loss. Given that a significant portion of individuals affected by traumatic bone defects in the craniofacial area belong to the aging population, there is an urgent need for innovative biomaterials to address the …

Self-Assembling Peptides As Immunomodulatory Biomaterials, Andrea Hernandez, Jeffrey D Hartgerink, Simon Young

Faculty, Staff and Student Publications

Self-assembling peptides are a type of biomaterial rapidly emerging in the fields of biomedicine and material sciences due to their promise in biocompatibility and effectiveness at controlled release. These self-assembling peptides can form diverse nanostructures in response to molecular interactions, making them versatile materials. Once assembled, the peptides can mimic biological functions and provide a combinatorial delivery of therapeutics such as cytokines and drugs. These self-assembling peptides are showing success in biomedical settings yet face unique challenges that must be addressed to be widely applied in the clinic. Herein, we describe self-assembling peptides' characteristics and current applications in immunomodulatory therapeutics.

Cancer-Associated Pyroptosis: A New License To Kill Tumor, Qing Kong, Zhibin Zhang

Faculty, Staff and Student Publications

Pyroptosis is a programmed necrotic cell death mediated by pore-forming Gasdermin (GSDM) proteins. After being unleashed from the C-terminal auto-inhibitory domains by proteolytic cleavage, the N-terminal domains of GSDMs oligomerize and perforate on the plasma membrane to induce cytolytic pyroptosis, releasing immune mediators and alarming the immune system. Upon infection or danger signal perception, GSDMD that functions downstream of the inflammasome, a supramolecular complex for inflammatory caspase activation, is cleaved and activated by inflammasome-activated caspase-1/4/5/11 in immune cells and epithelial cells to trigger pyroptosis and exert anti-infection protection. Unlike this inflammasome-activated pyroptosis (IAP), recent studies also suggest an emerging role …

Feasibility Of Quantitative Diffusion-Weighted Imaging During Intra-Procedural Mri-Guided Brachytherapy Of Locally Advanced Cervical And Vaginal Cancers, Megan C Jacobsen, Bastien Rigaud, Samantha J Simiele, Gaiane M Rauch, Matthew S Ning, Sastry Vedam, Ann H Klopp, R Jason Stafford, Kristy K Brock, Aradhana M Venkatesan

Faculty, Staff and Student Publications

Purpose: To determine the feasibility of quantitative apparent diffusion coefficient (ADC) acquisition during magnetic resonance imaging-guided brachytherapy (MRgBT) using reduced field-of-view (rFOV) diffusion-weighted imaging (DWI).

Methods and materials: T2-weighted (T2w) MR and full-FOV single-shot echo planar (ssEPI) DWI were acquired in 7 patients with cervical or vaginal malignancy at baseline and prior to brachytherapy, while rFOV-DWI was acquired during MRgBT following brachytherapy applicator placement. The gross target volume (GTV) was contoured on the T2w images and registered to the ADC map. Voxels at the GTV's maximum Maurer distance comprised a central sub-volume (GTVcenter). Contour ADC mean and standard deviation were …

Comparing The Microbiomes Of Dental Plaques In 19th Century Ancestral Remains, Ananya Udyaver

Undergraduate Research Posters

During the construction of VCU’s Hermes A. Kontos Medical Sciences Building in April 1994, nineteenth century ancestral remains were found in an abandoned well on the Medical College of Virginia (MCV) campus. This well, now known as the East Marshall Street Well (EMSW), is thought to have been used as a disposal location for cadaver dissection for surgical and other medical waste in the past. VCU is now seeking to use DNA sequencing technology to match and assemble bones from each individual for a proper burial, uncover the cultural and historical context in which these people lived, and bring a …

Investigation Of The Dyrk1a Regulation By Lzts2-Sipa1l1 Complex, Rebecca Gunnin, Austin Witt B.S., Larisa Litovchick M.D.,Ph.D.

Undergraduate Research Posters

A region on chromosome 21, the Down Syndrome critical region (DSCR), is associated with major defects found in Down Syndrome, such as craniofacial malformations. DYRK1A is a gene found on chromosome 21 within the DSCR that encodes an enzyme, dual specificity tyrosine-phosphorylation-regulated kinase 1A. DYRK1A is known to phosphorylate many substrate proteins and is thought to be involved in tumor suppression, neurological development, cell cycle regulation, and aging. Recently, the Litovchick lab and others reported that DYRK1A also plays a role in the double-strand break repair of DNA, which could lead to mutations and tumorigenesis, if deregulated.

The Litovchick lab …

A Single-Case Alternating Treatments Design Utilzing Quantitative Electroencephalography To Observe And Measure Mental State Trends During Individual Participant Non-Nature-Based Small Initiative Adventure Therapy Experiences, Patrick Lane Robert Mcmillion

Graduate Research Theses & Dissertations

This single-case alternating-treatments design research study observed and measured mental state trends during the counseling approach known as Adventure Therapy (AT) using quantitative electroencephalography (qEEG). Participants wore a qEEG headset while participating in a multi-stage AT experience. Two problems were addressed in this study. The first was the lack of research in AT utilizing other empirical measures beyond subjective report surveys and the outcomes of specific programs. The second was the lack of neuroscientific measurement of counseling approaches and interventions within the field of counseling in general. There is a need for empirical evidence supporting AT to address access barriers …