Medical Specialties Commons^™

Synovial Fibroblast Gene Expression Is Associated With Sensory Nerve Growth And Pain In Rheumatoid Arthritis, Zilong Bai, Nicholas Bartelo, Maryam Aslam, Elisabeth A Murphy, Caryn R Hale, Nathalie E Blachere, Salina Parveen, Edoardo Spolaore, Edward Dicarlo, Ellen M Gravallese, Melanie H Smith, Accelerating Medicines Partnership Ra/Sle Network, Mayu O Frank, Caroline S Jiang, Haotan Zhang, Christina Pyrgaki, Myles J Lewis, Shafaq Sikandar, Costantino Pitzalis, Joseph B Lesnak, Khadijah Mazhar, Theodore J Price, Anne-Marie Malfait, Rachel E Miller, Fan Zhang, Susan Goodman, Robert B Darnell, Fei Wang, Dana E Orange

Faculty, Staff and Student Publications

It has been presumed that rheumatoid arthritis (RA) joint pain is related to inflammation in the synovium; however, recent studies reveal that pain scores in patients do not correlate with synovial inflammation. We developed a machine-learning approach (graph-based gene expression module identification or GbGMI) to identify an 815-gene expression module associated with pain in synovial biopsy samples from patients with established RA who had limited synovial inflammation at arthroplasty. We then validated this finding in an independent cohort of synovial biopsy samples from patients who had early untreated RA with little inflammation. Single-cell RNA sequencing analyses indicated that most of …

Funcpep V20: An Updated Database Of Functional Short Peptides Translated From Non-Coding Rnas, Swati Mohapatra, Anik Banerjee, Paola Rausseo, Mihnea P Dragomir, Ganiraju C Manyam, Bradley M Broom, George A Calin

Faculty, Staff and Student Publications

Over the past decade, there have been reports of short novel functional peptides (less than 100 aa in length) translated from so-called non-coding RNAs (ncRNAs) that have been characterized using mass spectrometry (MS) and large-scale proteomics studies. Therefore, understanding the bivalent functions of some ncRNAs as transcripts that encode both functional RNAs and short peptides, which we named ncPEPs, will deepen our understanding of biology and disease. In 2020, we published the first database of functional peptides translated from non-coding RNAs-FuncPEP. Herein, we have performed an update including the newly published ncPEPs from the last 3 years along with the …

Author Correction: Comparative Analysis Of Dimension Reduction Methods For Cytometry By Time-Of-Flight Data, Kaiwen Wang, Yuqiu Yang, Fangjiang Wu, Bing Song, Xinlei Wang, Tao Wang

Faculty, Staff and Student Publications

No abstract provided.

The Roles Of Ferroptosis In Cancer: Tumor Suppression, Tumor Microenvironment, And Therapeutic Interventions, Guang Lei, Li Zhuang, Boyi Gan

Faculty, Staff and Student Publications

In cancer treatment, the recurrent challenge of inducing apoptosis through conventional therapeutic modalities, often thwarted by therapy resistance, emphasizes the critical need to explore alternative cell death pathways. Ferroptosis, an iron-dependent form of regulated cell death triggered by the lethal accumulation of lipid peroxides on cellular membranes, has emerged as one such promising frontier in oncology. Induction of ferroptosis not only suppresses tumor growth but also holds potential for augmenting immunotherapy responses and surmounting resistance to existing cancer therapies. This review navigates the role of ferroptosis in tumor suppression. Furthermore, we delve into the complex role of ferroptosis within the …

Arid1a Orchestrates Swi/Snf-Mediated Sequential Binding Of Transcription Factors With Arid1a Loss Driving Pre-Memory B Cell Fate And Lymphomagenesis, Darko Barisic, Christopher R Chin, Cem Meydan, Matt Teater, Ioanna Tsialta, Coraline Mlynarczyk, Amy Chadburn, Xuehai Wang, Margot Sarkozy, Min Xia, Sandra E Carson, Santo Raggiri, Sonia Debek, Benedikt Pelzer, Ceyda Durmaz, Qing Deng, Priya Lakra, Martin Rivas, Christian Steidl, David W Scott, Andrew P Weng, Christopher E Mason, Michael R Green, Ari Melnick

Faculty, Staff and Student Publications

ARID1A, a subunit of the canonical BAF nucleosome remodeling complex, is commonly mutated in lymphomas. We show that ARID1A orchestrates B cell fate during the germinal center (GC) response, facilitating cooperative and sequential binding of PU.1 and NF-kB at crucial genes for cytokine and CD40 signaling. The absence of ARID1A tilts GC cell fate toward immature IgM+CD80-PD-L2- memory B cells, known for their potential to re-enter new GCs. When combined with BCL2 oncogene, ARID1A haploinsufficiency hastens the progression of aggressive follicular lymphomas (FLs) in mice. Patients with FL with ARID1A-inactivating mutations preferentially display an immature memory B cell-like state with …

Smarca4 Is A Haploinsufficient B Cell Lymphoma Tumor Suppressor That Fine-Tunes Centrocyte Cell Fate Decisions, Qing Deng, Priya Lakra, Panhong Gou, Haopeng Yang, Cem Meydan, Matthew Teater, Christopher Chin, Wenchao Zhang, Tommy Dinh, Usama Hussein, Xubin Li, Estela Rojas, Weiguang Liu, Patrick K Reville, Atish Kizhakeyil, Darko Barisic, Sydney Parsons, Ashley Wilson, Jared Henderson, Brooks Scull, Channabasavaiah Gurumurthy, Francisco Vega, Amy Chadburn, Branko Cuglievan, Nader Kim El-Mallawany, Carl Allen, Christopher Mason, Ari Melnick, Michael R Green

Faculty, Staff and Student Publications

SMARCA4 encodes one of two mutually exclusive ATPase subunits in the BRG/BRM associated factor (BAF) complex that is recruited by transcription factors (TFs) to drive chromatin accessibility and transcriptional activation. SMARCA4 is among the most recurrently mutated genes in human cancer, including ∼30% of germinal center (GC)-derived Burkitt lymphomas. In mice, GC-specific Smarca4 haploinsufficiency cooperated with MYC over-expression to drive lymphomagenesis. Furthermore, monoallelic Smarca4 deletion drove GC hyperplasia with centroblast polarization via significantly increased rates of centrocyte recycling to the dark zone. Mechanistically, Smarca4 loss reduced the activity of TFs that are activated in centrocytes to drive GC-exit, including SPI1 …

Arterial Spin-Labeling And Dsc Perfusion Metrics Improve Agreement In Neuroradiologists' Clinical Interpretations Of Posttreatment High-Grade Glioma Surveillance Mr Imaging-An Institutional Experience, Ghiam Yamin, Eric Tranvinh, Bryan A Lanzman, Elizabeth Tong, Syed S Hashmi, Chirag B Patel, Michael Iv

Faculty, Staff and Student Publications

Background and purpose: MR perfusion has shown value in the evaluation of posttreatment high-grade gliomas, but few studies have shown its impact on the consistency and confidence of neuroradiologists' interpretation in routine clinical practice. We evaluated the impact of adding MR perfusion metrics to conventional contrast-enhanced MR imaging in posttreatment high-grade glioma surveillance imaging.

Materials and methods: This retrospective study included 45 adults with high-grade gliomas who had posttreatment perfusion MR imaging. Four neuroradiologists assigned Brain Tumor Reporting and Data System scores for each examination on the basis of the interpretation of contrast-enhanced MR imaging and then after the addition …

The Hallmarks Of Precancer, Mary M Stangis, Zhengyi Chen, Jimin Min, Sarah E Glass, Jordan O Jackson, Megan D Radyk, Xen Ping Hoi, W Nathaniel Brennen, Ming Yu, Huy Q Dinh, Robert J Coffey, Martha J Shrubsole, Keith S Chan, William M Grady, Srinivasan Yegnasubramanian, Costas A Lyssiotis, Anirban Maitra, Richard B Halberg, Neelendu Dey, Ken S Lau

Faculty, Staff and Student Publications

Research on precancers, as defined as at-risk tissues and early lesions, is of high significance given the effectiveness of early intervention. We discuss the need for risk stratification to prevent overtreatment, an emphasis on the role of genetic and epigenetic aging when considering risk, and the importance of integrating macroenvironmental risk factors with molecules and cells in lesions and at-risk normal tissues for developing effective intervention and health policy strategies.

T-Cell Dysfunctions In Myelodysplastic Syndromes, Juan Jose Rodriguez-Sevilla, Simona Colla

Faculty, Staff and Student Publications

Escape from immune surveillance is a hallmark of cancer. Immune deregulation caused by intrinsic and extrinsic cellular factors, such as altered T-cell functions, leads to immune exhaustion, loss of immune surveillance, and clonal proliferation of tumoral cells. The T-cell immune system contributes to the pathogenesis, maintenance, and progression of myelodysplastic syndrome (MDS). Here, we comprehensively reviewed our current biological knowledge of the T-cell compartment in MDS and recent advances in the development of immunotherapeutic strategies, such as immune checkpoint inhibitors and T-cell- and antibody-based adoptive therapies that hold promise to improve the outcome of patients with MDS.

Oncogenic Oral Human Papillomavirus Clearance Patterns Over 10 Years, Gypsyamber D'Souza, Sakshi R Tewari, Tanya Troy, Jennifer Webster-Cyriaque, Dorothy J Wiley, Cecile Delille Lahiri, Frank Joseph Palella, Maura L Gillison, Howard D Strickler, Linda Struijk, Tim Waterboer, Ken Ho, Jennafer Kwait, Jason Lazar, Kathleen M Weber, Carole Fakhry

Faculty, Staff and Student Publications

Background: Effective screening for oropharyngeal cancer is lacking. Four oncogenic HPV clearance definitions were explored to understand long-term natural history for persistent oncogenic oral HPV (oncHPV), the precursor of oropharyngeal cancer.

Methods: Prospective multicenter cohort of participants living with/at-risk for HIV, with oral rinse and gargle samples collected every 6 to 12 months for up to 10 years and tested for oncHPV. HPV clearance definitions included 1 (clear1), 2 (clear2), 3 (clear3) consecutive negatives, or being negative at last two visits (clearlast).

Results: Median time to clearance of oncHPV exceeded 2 years for conservative definitions (clear3: 2.38, clearlast: 2.43), but …

Nodal Variants Are Associated With A Continuum Of Laterality Defects From Simple D-Transposition Of The Great Arteries To Heterotaxy, Zain Dardas, Jawid M Fatih, Angad Jolly, Moez Dawood, Haowei Du, Christopher M Grochowski, Edward G Jones, Shalini N Jhangiani, Xander H T Wehrens, Pengfei Liu, Weimin Bi, Eric Boerwinkle, Jennifer E Posey, Donna M Muzny, Richard A Gibbs, James R Lupski, Zeynep Coban-Akdemir, Shaine A Morris

Faculty, Staff and Student Publications

BACKGROUND: NODAL signaling plays a critical role in embryonic patterning and heart development in vertebrates. Genetic variants resulting in perturbations of the TGF-β/NODAL signaling pathway have reproducibly been shown to cause laterality defects in humans. To further explore this association and improve genetic diagnosis, the study aims to identify and characterize a broader range of NODAL variants in a large number of individuals with laterality defects.

METHODS: We re-analyzed a cohort of 321 proband-only exomes of individuals with clinically diagnosed laterality congenital heart disease (CHD) using family-based, rare variant genomic analyses. To this cohort we added 12 affected subjects with …

Author Correction: Automating Data Analysis For Hydrogen/Deuterium Exchange Mass Spectrometry Using Data-Independent Acquisition Methodology, Frantisek Filandr, Vladimir Sarpe, Shaunak Raval, D Alex Crowder, Morgan F Khan, Pauline Douglas, Stephen Coales, Rosa Viner, Aleem Syed, John A Tainer, Susan P Lees-Miller, David C Schriemer

Faculty, Staff and Student Publications

No abstract provided.

Glial Lipid Droplets Resolve Ros During Sleep, Lindsey D Goodman, Matthew J Moulton, Hugo J Bellen

Duncan NRI Faculty and Staff Publications

The Sehgal lab presents data showing that the non-cell autonomous pathway of glial lipid droplet formation occurs during sleep and helps to resolve neuronal reactive oxygen species (ROS). This promotes neuronal function after an active day. Hence, this pathway has an important physiological function beyond its previously described role in ROS-associated diseases, including Alzheimer’s disease.

Unveiling Gene Interactions In Alzheimer's Disease By Integrating Genetic And Epigenetic Data With A Network-Based Approach, Keith L Sanders, Astrid M Manuel, Andi Liu, Boyan Leng, Xiangning Chen, Zhongming Zhao

Faculty, Staff and Student Publications

Alzheimer’s Disease (AD) is a complex disease and the leading cause of dementia in older people. We aimed to uncover aspects of AD’s pathogenesis that may contribute to drug repurposing efforts by integrating DNA methylation and genetic data. Implementing the network-based tool, a dense module search of genome-wide association studies (dmGWAS), we integrated a large-scale GWAS dataset with DNA methylation data to identify gene network modules associated with AD. Our analysis yielded 286 significant gene network modules. Notably, the foremost module included the BIN1 gene, showing the largest GWAS signal, and the GNAS gene, the most significantly hypermethylated. We conducted …

Social And Behavior Factors Of Alzheimer's Disease And Related Dementias: A National Study In The Us, David Ciciora, Elizabeth Vásquez, Edward Valachovic, Lifang Hou, Yinan Zheng, Hua Xu, Xiaoqian Jiang, Kun Huang, Kelley Pettee Gabriel, Hong-Wen Deng, Mary P Gallant, Kai Zhang

Faculty, Staff and Student Publications

Introduction: Considerable research has linked many risk factors to Alzheimer's Disease and Related Dementias (ADRD). Without a clear etiology of ADRD, it is advantageous to rank the known risk factors by their importance and determine if disparities exist. Statistical-based ranking can provide insight into which risk factors should be further evaluated.

Methods: This observational, population-based study assessed 50 county-level measures and estimates related to ADRD in 3,155 counties in the U.S. using data from 2010 to 2021. Statistical analysis was performed in 2022-2023. The machine learning method, eXtreme Gradient Boosting, was utilized to rank the importance of these variables by …

Signaling Mechanisms Underlying Activity-Dependent Integration Of Adult-Born Neurons In The Mouse Olfactory Bulb, Suyang Bao, Juan M Romero, Benjamin D W Belfort, Benjamin R Arenkiel

Duncan NRI Faculty and Staff Publications

Adult neurogenesis has fascinated the field of neuroscience for decades given the prospects of harnessing mechanisms that facilitate the rewiring and/or replacement of adult brain tissue. The subgranular zone of the hippocampus and the subventricular zone of the lateral ventricle are the two main areas in the brain that exhibit ongoing neurogenesis. Of these, adult-born neurons within the olfactory bulb have proven to be a powerful model for studying circuit plasticity, providing a broad and accessible avenue into neuron development, migration, and continued circuit integration within adult brain tissue. This review focuses on some of the recognized molecular and signaling …

Systemic Neutrophil Gelatinase-Associated Lipocalin Alterations In Chronic Pancreatitis: A Multicenter, Cross-Sectional Study, Kristyn Gumpper-Fedus, Kaylin Chasser, Valentina Pita-Grisanti, Molly Torok, Timothy Pfau, Thomas A Mace, Rachel M Cole, Martha A Belury, Stacey Culp, Phil A Hart, Somashekar G Krishna, Luis F Lara, Mitchell L Ramsey, William Fisher, Evan L Fogel, Chris E Forsmark, Liang Li, Stephen Pandol, Walter G Park, Jose Serrano, Stephen K Van Den Eeden, Santhi Swaroop Vege, Dhiraj Yadav, Darwin L Conwell, Zobeida Cruz-Monserrate, Consortium For The Study Of Chronic Pancreatitis, Diabetes, And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Student Publications

Introduction: Chronic pancreatitis (CP) is a progressive fibroinflammatory disorder lacking therapies and biomarkers. Neutrophil gelatinase-associated lipocalin (NGAL) is a proinflammatory cytokine elevated during inflammation that binds fatty acids (FAs) such as linoleic acid. We hypothesized that systemic NGAL could serve as a biomarker for CP and, with FAs, provide insights into inflammatory and metabolic alterations.

Methods: NGAL was measured by immunoassay, and FA composition was measured by gas chromatography in plasma (n = 171) from a multicenter study, including controls (n = 50), acute and recurrent acute pancreatitis (AP/RAP) (n = 71), and CP (n = 50). Peripheral blood mononuclear …

Premastectomy Radiotherapy And Immediate Breast Reconstruction: A Randomized Clinical Trial, Mark V Schaverien, Puneet Singh, Benjamin D Smith, Wei Qiao, Catherine L Akay, Elizabeth S Bloom, Mariana Chavez-Macgregor, Carrie K Chu, Mark W Clemens, Jessica S Colen, Richard A Ehlers, Rosa F Hwang, Melissa M Joyner, Rene D Largo, Alexander F Mericli, Melissa P Mitchell, John W Shuck, Nina Tamirisa, Debasish Tripathy, Mark T Villa, Wendy A Woodward, Rensi Zacharia, Henry M Kuerer, Karen E Hoffman

Faculty, Staff and Student Publications

Importance: Premastectomy radiotherapy (PreMRT) is a new treatment sequence to avoid the adverse effects of radiotherapy on the final breast reconstruction while achieving the benefits of immediate breast reconstruction (IMBR).

Objective: To evaluate outcomes among patients who received PreMRT and regional nodal irradiation (RNI) followed by mastectomy and IMBR.

Design, setting, and participants: This was a phase 2 single-center randomized clinical trial conducted between August 3, 2018, and August 2, 2022, evaluating the feasibility and safety of PreMRT and RNI (including internal mammary lymph nodes). Patients with cT0-T3, N0-N3b breast cancer and a recommendation for radiotherapy were eligible.

Intervention: This …

Flexible Bayesian Product Mixture Models For Vector Autoregressions, Suprateek Kundu, Joshua Lukemire

Faculty, Staff and Student Publications

Bayesian non-parametric methods based on Dirichlet process mixtures have seen tremendous success in various domains and are appealing in being able to borrow information by clustering samples that share identical parameters. However, such methods can face hurdles in heterogeneous settings where objects are expected to cluster only along a subset of axes or where clusters of samples share only a subset of identical parameters. We overcome such limitations by developing a novel class of product of Dirichlet process location-scale mixtures that enables independent clustering at multiple scales, which results in varying levels of information sharing across samples. First, we develop …

Fear Antiviral Response Pathway Is Independent Of Interferons And Countered By Poxvirus Proteins, Emily A Rex, Dahee Seo, Sruthi Chappidi, Chelsea Pinkham, Sabrynna Brito Oliveira, Aaron Embry, David Heisler, Yang Liu, Moiz Munir, Karolin Luger, Neal M Alto, Flávio Guimarães Da Fonseca, Robert Orchard, Dustin C Hancks, Don B Gammon

Faculty, Staff and Student Publications

The human facilitates chromatin transcription (FACT) complex is a chromatin remodeller composed of human suppressor of Ty 16 homologue (hSpt16) and structure-specific recognition protein-1 subunits that regulates cellular gene expression. Whether FACT regulates host responses to infection remained unclear. We identify a FACT-mediated, interferon-independent, antiviral pathway that restricts poxvirus replication. Cell culture and bioinformatics approaches suggest that early viral gene expression triggers nuclear accumulation of SUMOylated hSpt16 subunits required for the expression of E26 transformation-specific sequence-1 (ETS-1)-a transcription factor that activates virus restriction programs. However, biochemical studies show that poxvirus-encoded A51R proteins block ETS-1 expression by outcompeting structure-specific recognition protein-1 …

Delta Radiomic Features Predict Resection Margin Status And Overall Survival In Neoadjuvant-Treated Pancreatic Cancer Patients, Kai Wang, John D Karalis, Ahmed Elamir, Alessandro Bifolco, Megan Wachsmann, Giovanni Capretti, Paola Spaggiari, Sebastian Enrico, Kishore Balasubramanian, Nafeesah Fatimah, Giada Pontecorvi, Martina Nebbia, Adam Yopp, Ravi Kaza, Ivan Pedrosa, Herbert Zeh, Patricio Polanco, Alessandro Zerbi, Jing Wang, Todd Aguilera, Matteo Ligorio

Faculty, Staff and Student Publications

Background: Neoadjuvant therapy (NAT) emerged as the standard of care for patients with pancreatic ductal adenocarcinoma (PDAC) who undergo surgery; however, surgery is morbid, and tools to predict resection margin status (RMS) and prognosis in the preoperative setting are needed. Radiomic models, specifically delta radiomic features (DRFs), may provide insight into treatment dynamics to improve preoperative predictions.

Methods: We retrospectively collected clinical, pathological, and surgical data (patients with resectable, borderline, locally advanced, and metastatic disease), and pre/post-NAT contrast-enhanced computed tomography (CT) scans from PDAC patients at the University of Texas Southwestern Medical Center (UTSW; discovery) and Humanitas Hospital (validation cohort). …

Recurrent Lymphoid And Myeloid Relapses Due To Treatment Cessations Reveal Natural History Of Ph-Positive B-All And Pose A Diagnostic Challenge, Shimin Hu, Elias J Jabbour, Collin Y Hu, Guilin Tang, Wei Wang, L Jeffrey Medeiros, Carlos Bueso-Ramos

Faculty, Staff and Student Publications

No abstract provided.

Bone Marrow-Restricted Aberrant Myeloperoxidase Expression In B-Acute Lymphoblastic Leukemia: A Diagnostic Dilemma And Mimicry Of Mixed Phenotype Acute Leukemia, Wei J Wang, Brandon T Gehris, Daniel Rivera, Sibel Ak, David Feng, Wei Wang, Zhihong Hu

Faculty, Staff and Student Publications

Myeloperoxidase (MPO) is the most specific marker of the myeloid lineage, essential for diagnosing acute myeloid leukemia and mixed phenotype acute leukemia with myeloid components. In this regard, we present a unique case of B-acute lymphoblastic leukemia (B-ALL) with isolated MPO expression in bone marrow blasts detected by flow cytometry and immunohistochemistry, while peripheral blood blasts were negative for MPO expression. In this report, our discussion encompasses diagnostic pitfalls from a laboratory testing perspective in similar cases and includes a literature review. Furthermore, we emphasize the necessity of conducting a comprehensive analysis for the accurate diagnosis of MPO-positive B-ALL cases.

Diagnostic Utility Of Immunohistochemistry In Detection Of Npm1 Mutations In Acute Myeloid Leukemia With A Patchy Distribution, Qing Wei, Sa A Wang, Sanam Loghavi, Hong Fang, L Jeffrey Medeiros, Wei Wang

Faculty, Staff and Student Publications

Nucleophosmin 1 (NPM1) mutations occur in approximately one‐third cases of adult de novo acute myeloid leukemia (AML). Identification of NPM1 mutations is important for classification, risk stratification, tailored therapy, and monitoring minimal residual disease. Mutational analysis is widely used for detecting NPM1 mutations. Immunochemistry assessing abnormal cytoplasmic localization of NPM1 protein has been used as a surrogate marker for NPM1 mutations. We present a case of AML with mutated NPM1 that was missed by sequencing analysis but detected by immunohistochemistry. This case highlights the value of immunohistochemistry in identifying NPM1 mutations in a subset of AML cases.

Alk-Positive Histiocytosis Of External Auditory Canal In A 3-Year-Old Boy, Shu-Hsien Wang, Hsuan-Ying Huang, L Jeffrey Medeiros, Kung-Chao Chang

Faculty, Staff and Student Publications

No abstract provided.

Socioeconomic Status And Chronic Health Conditions In Asian Survivors Of Adolescent And Young Adult Cancers, Amy M Berkman, Eunju Choi, Christabel K Cheung, John M Salsman, Susan K Peterson, Clark R Andersen, Qian Lu, J Andrew Livingston, Michelle A T Hildebrandt, Susan K Parsons, Michael E Roth

Faculty, Staff and Student Publications

Purpose: While there are known disparities in socioeconomic status (SES) and health outcomes among racially and ethnically minoritized adolescent and young adult (AYA; ages 15-39 years at diagnosis) cancer survivors compared with White survivors, outcomes in the Asian survivor population are understudied. To better understand the association of an AYA cancer diagnosis with SES and health outcomes within a minoritized population, the current study makes comparisons between individuals of the same race or ethnicity with and without a history of AYA cancer.

Methods: Non-Hispanic, Asian AYA cancer survivors and non-Hispanic, Asian age- and sex-matched controls were identified from self-reported data …

Temporal Changes In Treatment And Late Mortality And Morbidity In Adult Survivors Of Childhood Glioma: A Report From The Childhood Cancer Survivor Study, Peter M K De Blank, Katharine R Lange, Mengqi Xing, Sedigheh Mirzaei Salehabadi, Deokumar Srivastava, Tara M Brinkman, Kirsten K Ness, Kevin C Oeffinger, Joseph Neglia, Kevin R Krull, Paul C Nathan, Rebecca Howell, Lucie M Turcotte, Wendy Leisenring, Gregory T Armstrong, M Fatih Okcu, Daniel C Bowers

Faculty, Staff and Student Publications

Pediatric glioma therapy has evolved to delay or eliminate radiation for low-grade tumors. This study examined these temporal changes in therapy with long-term outcomes in adult survivors of childhood glioma. Among 2,501 5-year survivors of glioma in the Childhood Cancer Survivor Study diagnosed 1970-1999, exposure to radiation decreased over time. Survivors from more recent eras were at lower risk of late mortality (≥5 years from diagnosis), severe/disabling/life-threatening chronic health conditions (CHCs) and subsequent neoplasms (SNs). Adjusting for treatment exposure (surgery only, chemotherapy, or any cranial radiation) attenuated this risk (for example, CHCs (1990s versus 1970s), relative risk (95% confidence interval), …

Survival Outcomes And Toxicity Of Adjuvant Immunotherapy After Definitive Concurrent Chemotherapy With Proton Beam Radiation Therapy For Patients With Inoperable Locally Advanced Non-Small Cell Lung Carcinoma, Kelsey L Corrigan, Ting Xu, Yuki Sasaki, Ruitao Lin, Aileen B Chen, James W Welsh, Steven H Lin, Joe Y Chang, Matthew S Ning, Saumil Gandhi, Michael S O'Reilly, Carl M Gay, Mehmet Altan, Charles Lu, Tina Cascone, Efstratios Koutroumpakis, Ajay Sheshadri, Xiaodong Zhang, Li Liao, X Ronald Zhu, John V Heymach, Quynh-Nhu Nguyen, Zhongxing Liao

Faculty, Staff and Student Publications

Introduction: Adjuvant immunotherapy (IO) following concurrent chemotherapy and photon radiation therapy confers an overall survival (OS) benefit for patients with inoperable locally advanced non-small cell lung carcinoma (LA-NSCLC); however, outcomes of adjuvant IO after concurrent chemotherapy with proton beam therapy (CPBT) are unknown. We investigated OS and toxicity after CPBT with adjuvant IO versus CPBT alone for inoperable LA-NSCLC.

Materials and methods: We analyzed 354 patients with LA-NSCLC who were prospectively treated with CPBT with or without adjuvant IO from 2009 to 2021. Optimal variable ratio propensity score matching (PSM) matched CPBT with CPBT + IO patients. Survival was estimated …

Loss-Of-Function Mutation In Prmt9 Causes Abnormal Synapse Development By Dysregulation Of Rna Alternative Splicing, Lei Shen, Xiaokuang Ma, Yuanyuan Wang, Zhihao Wang, Yi Zhang, Hoang Quoc Hai Pham, Xiaoqun Tao, Yuehua Cui, Jing Wei, Dimitri Lin, Tharindumala Abeywanada, Swanand Hardikar, Levon Halabelian, Noah Smith, Taiping Chen, Dalia Barsyte-Lovejoy, Shenfeng Qiu, Yi Xing, Yanzhong Yang

Faculty, Staff and Student Publications

Protein arginine methyltransferase 9 (PRMT9) is a recently identified member of the PRMT family, yet its biological function remains largely unknown. Here, by characterizing an intellectual disability associated PRMT9 mutation (G189R) and establishing a Prmt9 conditional knockout (cKO) mouse model, we uncover an important function of PRMT9 in neuronal development. The G189R mutation abolishes PRMT9 methyltransferase activity and reduces its protein stability. Knockout of Prmt9 in hippocampal neurons causes alternative splicing of ~1900 genes, which likely accounts for the aberrant synapse development and impaired learning and memory in the Prmt9 cKO mice. Mechanistically, we discover a methylation-sensitive protein-RNA interaction between …

Oral Decitabine And Cedazuridine Plus Venetoclax For Older Or Unfit Patients With Acute Myeloid Leukaemia: A Phase 2 Study, Alexandre Bazinet, Guillermo Garcia-Manero, Nicholas Short, Yesid Alvarado, Alex Bataller, Tareq Abuasab, Rabiul Islam, Kathryn Montalbano, Ghayas Issa, Abhishek Maiti, Musa Yilmaz, Nitin Jain, Lucia Masarova, Steven Kornblau, Elias Jabbour, Guillermo Montalban-Bravo, Caitlin R Rausch, Sherry Pierce, Courtney D Dinardo, Tapan Kadia, Naval Daver, Marina Konopleva, Xuelin Huang, Hagop Kantarjian, Farhad Ravandi

Faculty, Staff and Student Publications

Background: Hypomethylating agents combined with venetoclax are effective regimens in patients with acute myeloid leukaemia who are ineligible for intensive chemotherapy. Decitabine and cedazuridine (ASTX727) is an oral formulation of decitabine that achieves equivalent area-under-curve exposure to intravenous decitabine. We performed a single centre phase 2 study to evaluate the efficacy and safety of ASTX727 plus venetoclax.

Methods: This study enrolled patients with newly diagnosed (frontline treatment group) acute myeloid leukaemia who were ineligible for intensive chemotherapy (aged ≥75 years, an Eastern Cooperative Oncology Group [ECOG] performance status of 2-3, or major comorbidities) or relapsed or refractory acute myeloid leukaemia. …