Medical Specialties Commons^™

Mechanism And Rational Combinations With Gp-2250, A Novel Oxathiazine Derivative, In Ovarian Cancer, Mark S Kim, Deanna Glassman, Katelyn F Handley, Adrian Lankenau Ahumada, Nicholas B Jennings, Emine Bayraktar, Katherine Foster, Robiya Joseph, Sanghoon Lee, Robert L Coleman, Anil K Sood

Faculty, Staff and Student Publications

BACKGROUND: GP-2250, a novel analog of taurultam (TRLT), has emerged as a potent anti-neoplastic drug; however, the mechanisms underlying its effects are not well understood. Here, we investigated the mechanism of action and the biological effects of GP-2250 using in vitro and in vivo models.

METHODS: We carried out a series of in vitro (MTT assay, Annexin V/PI assay, colony formation assay, reverse-phase protein array [RPPA], and HRLC/IC analysis) to determine the biological activity of GP-2250 and investigate the mechanism of action. In vivo experiments were carried out to determine the therapeutic efficacy of GP-2250 alone and in combination with …

Autophagic Signaling Promotes Systems-Wide Remodeling In Skeletal Muscle Upon Oncometabolic Stress By D2-Hg, Yaqi Gao, Kyoungmin Kim, Heidi Vitrac, Rebecca L Salazar, Benjamin D Gould, Daniel Soedkamp, Weston Spivia, Koen Raedschelders, An Q Dinh, Anna G Guzman, Lin Tan, Stavros Azinas, David J R Taylor, Walter Schiffer, Daniel Mcnavish, Helen B Burks, Roberta A Gottlieb, Philip L Lorenzi, Blake M Hanson, Jennifer E Van Eyk, Heinrich Taegtmeyer, Anja Karlstaedt

Faculty, Staff and Student Publications

OBJECTIVES: Cachexia is a metabolic disorder and comorbidity with cancer and heart failure. The syndrome impacts more than thirty million people worldwide, accounting for 20% of all cancer deaths. In acute myeloid leukemia, somatic mutations of the metabolic enzyme isocitrate dehydrogenase 1 and 2 cause the production of the oncometabolite D2-hydroxyglutarate (D2-HG). Increased production of D2-HG is associated with heart and skeletal muscle atrophy, but the mechanistic links between metabolic and proteomic remodeling remain poorly understood. Therefore, we assessed how oncometabolic stress by D2-HG activates autophagy and drives skeletal muscle loss.

METHODS: We quantified genomic, metabolomic, and proteomic changes in …

#Hashtagthis – Everything You Need To Know About Launching Your Gynecologic Oncology Social Media Research Career: A Report From Gynecologic Oncology Reports And Society Of Gynecologic Oncology Education Committee, Megan L Hutchcraft, Eric Rios-Doria, Tiffany Y Sia, Eleonora Teplinsky, Shannon N Westin, Gregg Nelson

Faculty, Staff and Student Publications

On February 6th, 2024, Gynecologic Oncology Reports and the Society of Gynecologic Oncology Education Committee co-hosted a webinar about ways to use social media for career enhancement and for dissemination of research. During the discussion, we reviewed:i.how to identify one's goals, target audience, and select a social media platform.ii.how to navigate the negatives of social media.iii.how to develop one's online academic brand.iv.how to use social media for academic promotion and career advancement.v.how to use social media as a research tool.vi.how to use visual tools to bring attention to one's research.The objective of this report is to review the literature on …

A Biallelic Variant Of The Rna Exosome Gene, Exosc4, Associated With Neurodevelopmental Defects Impairs Rna Exosome Function And Translation, Milo B Fasken, Sara W Leung, Lauryn A Cureton, Maha Al-Awadi, Adila Al-Kindy, Ambro Van Hoof, Sohail Khoshnevis, Homa Ghalei, Almundher Al-Maawali, Anita H Corbett

Faculty, Staff and Student Publications

The RNA exosome is an evolutionarily conserved complex required for both precise RNA processing and decay. Pathogenic variants in EXOSC genes, which encode structural subunits of this complex, are linked to several autosomal recessive disorders. Here, we describe a missense allele of the EXOSC4 gene that causes a collection of clinical features in two affected siblings. This missense variant (NM_019037.3: exon3:c.560T>C) changes a leucine residue within a conserved region of EXOSC4 to proline (p.Leu187Pro). The two affected individuals show prenatal growth restriction, failure to thrive, global developmental delay, intracerebral and basal ganglia calcifications, and kidney failure. Homozygosity for the …

Nf1 Mutation Disrupts Activity-Dependent Oligodendroglial Plasticity And Motor Learning In Mice, Yuan Pan, Jared D Hysinger, Belgin Yalçın, James J Lennon, Youkyeong Gloria Byun, Preethi Raghavan, Nicole F Schindler, Corina Anastasaki, Jit Chatterjee, Lijun Ni, Haojun Xu, Karen Malacon, Samin M Jahan, Alexis E Ivec, Benjamin E Aghoghovwia, Christopher W Mount, Surya Nagaraja, Suzanne Scheaffer, Laura D Attardi, David H Gutmann, Michelle Monje

Faculty, Staff and Student Publications

Neurogenetic disorders, such as neurofibromatosis type 1 (NF1), can cause cognitive and motor impairments, traditionally attributed to intrinsic neuronal defects such as disruption of synaptic function. Activity-regulated oligodendroglial plasticity also contributes to cognitive and motor functions by tuning neural circuit dynamics. However, the relevance of oligodendroglial plasticity to neurological dysfunction in NF1 is unclear. Here we explore the contribution of oligodendrocyte progenitor cells (OPCs) to pathological features of the NF1 syndrome in mice. Both male and female littermates (4-24 weeks of age) were used equally in this study. We demonstrate that mice with global or OPC-specific Nf1 heterozygosity exhibit defects …

A Visualization And Radiation Treatment Plan Quality Scoring Method For Triage In A Population-Based Context, Alexandra O Leone, Abdallah S R Mohamed, Clifton D Fuller, Christine B Peterson, Adam S Garden, Anna Lee, Lauren L Mayo, Amy C Moreno, Jay P Reddy, Karen Hoffman, Joshua S Niedzielski, Laurence E Court, Thomas J Whitaker

Faculty, Staff and Student Publications

PURPOSE: Our purpose was to develop a clinically intuitive and easily understandable scoring method using statistical metrics to visually determine the quality of a radiation treatment plan.

METHODS AND MATERIALS: Data from 111 patients with head and neck cancer were used to establish a percentile-based scoring system for treatment plan quality evaluation on both a plan-by-plan and objective-by-objective basis. The percentile scores for each clinical objective and the overall treatment plan score were then visualized using a daisy plot. To validate our scoring method, 6 physicians were recruited to assess 60 plans, each using a scoring table consisting of a …

Safety And Activity Of Lenalidomide In Combination With Obinutuzumab In Patients With Relapsed Indolent Non-Hodgkin Lymphoma: A Single Group, Open-Label, Phase 1/2 Trial, Ashwath Gurumurthi, Collin K Chin, Lei Feng, Nathan H Fowler, Paolo Strati, Fredrick B Hagemeister, Luis E Fayad, Jason R Westin, Chizobam Obi, Janine Arafat, Ranjit Nair, Raphael E Steiner, Sattva S Neelapu, Christopher R Flowers, Loretta J Nastoupil

Faculty, Staff and Student Publications

BACKGROUND: Rituximab and lenalidomide is a preferred option for relapsed indolent B cell non-Hodgkin lymphoma. Obinutuzumab may be a superior combination partner with lenalidomide given enhanced antibody dependent cellular cytotoxicity and phagocytosis compared to rituximab. Our aim was to determine the recommended phase 2 dose, safety, and activity of lenalidomide in combination with fixed dose of obinutuzumab in relapsed and refractory indolent B cell non-Hodgkin lymphoma.

METHODS: In this single-arm, open-label, phase 1/2 trial, we enrolled patients with relapsed or refractory WHO Grade 1-3A follicular lymphoma, marginal zone lymphoma and small lymphocytic lymphoma and adequate performance status (ECOG 0-2) at …

Molecular Responses In Decitabine- And Decitabine/ Venetoclax-Treated Patients With Acute Myeloid Leukemia And Myelodysplastic Syndromes, Agata Gruszczynska, Abhishek Maiti, Christopher A Miller, Sai Mukund Ramakrishnan, Daniel C Link, Geoffrey L Uy, Allegra A Petti, Kala Hayes, Courtney D Dinardo, Farhad Ravandi, Timothy J Ley, David H Spencer, Feng Gao, Marina Y Konopleva, John S Welch

Faculty, Staff and Student Publications

No abstract provided.

Enolase Inhibitors As Therapeutic Leads For Naegleria Fowleri Infection, Jillian E Milanes, Victoria C Yan, Cong-Dat Pham, Florian Muller, Samuel Kwain, Kerrick C Rees, Brian N Dominy, Daniel C Whitehead, Steven W Millward, Madison Bolejack, Roger Shek, Logan Tillery, Isabelle Q Phan, Bart Staker, E Ashley Moseman, Xiang Zhang, Xipeng Ma, Audriy Jebet, Xinmin Yin, James C Morris

Faculty, Staff and Student Publications

Infections with the pathogenic free-living amoebae Naegleria fowleri can lead to life-threatening illnesses including catastrophic primary amoebic meningoencephalitis (PAM). Efficacious treatment options for these infections are lacking and the mortality rate remains >95% in the US. Glycolysis is very important for the infectious trophozoite lifecycle stage and inhibitors of glucose metabolism have been found to be toxic to the pathogen. Recently, human enolase 2 (ENO2) phosphonate inhibitors have been developed as lead agents to treat glioblastoma multiforme (GBM). These compounds, which cure GBM in a rodent model, are well-tolerated in mammals because enolase 1 (ENO1) is the predominant isoform used …

Mapping The Single-Cell Differentiation Landscape Of Osteosarcoma, Danh D Truong, Corey Weistuch, Kevin A Murgas, Prasad Admane, Bridgette L King, Jes Chauviere Lee, Salah-E Lamhamedi-Cherradi, Jyothishmathi Swaminathan, Najat C Daw, Nancy Gordon, Vidya Gopalakrishnan, Richard G Gorlick, Neeta Somaiah, Joseph O Deasy, Antonios G Mikos, Allen Tannenbaum, Joseph Ludwig

Faculty, Staff and Student Publications

Purpose: The genetic intratumoral heterogeneity observed in human osteosarcomas poses challenges for drug development and the study of cell fate, plasticity, and differentiation, which are processes linked to tumor grade, cell metastasis, and survival.

Experimental design: To pinpoint errors in osteosarcoma differentiation, we transcriptionally profiled 31,527 cells from a tissue-engineered model that directs mesenchymal stem cells toward adipogenic and osteoblastic fates. Incorporating preexisting chondrocyte data, we applied trajectory analysis and non-negative matrix factorization to generate the first human mesenchymal differentiation atlas.

Results: This "roadmap" served as a reference to delineate the cellular composition of morphologically complex osteosarcoma tumors and quantify …

A 3d Dual-Echo Spiral Sequence For Simultaneous Dynamic Susceptibility Contrast And Dynamic Contrast-Enhanced Mri With Single Bolus Injection, Zhiqiang Li, Dinghui Wang, Melvyn B Ooi, Poonam Choudhary, Sudarshan Ragunathan, John P Karis, James G Pipe, C Chad Quarles, Ashley M Stokes

Faculty, Staff and Student Publications

Purpose: Perfusion MRI reveals important tumor physiological and pathophysiologic information, making it a critical component in managing brain tumor patients. This study aimed to develop a dual-echo 3D spiral technique with a single-bolus scheme to simultaneously acquire both dynamic susceptibility contrast (DSC) and dynamic contrast-enhanced (DCE) data and overcome the limitations of current EPI-based techniques.

Methods: A 3D spiral-based technique with dual-echo acquisition was implemented and optimized on a 3T MRI scanner with a spiral staircase trajectory and through-plane SENSE acceleration for improved speed and image quality, in-plane variable-density undersampling combined with a sliding-window acquisition and reconstruction approach for increased …

A Randomised, Parallel-Group, Double-Blind, Placebo-Controlled Phase 3 Study To Determine The Effectiveness Of The Type I Interferon Receptor Antibody, Anifrolumab, In Systemic Sclerosis: Daisy Study Design And Rationale, Dinesh Khanna, Christopher P Denton, Shervin Assassi, Masataka Kuwana, Yannick Allanore, Robyn T Domsic, Christi Kleoudis, John Xu, Eszter Csomor, Caroline Seo, Marius Albulescu, Raj Tummala, Hussein Al-Mossawi, Rubana N Kalyani, Francesco Del Galdo

Faculty, Staff and Student Publications

Objectives: The type I interferon pathway is a promising target for treatment of patients with systemic sclerosis (SSc). Here, we describe the design of a multinational, randomised phase 3 study to Determine the effectiveness of the type I interferon receptor antibody, Anifrolumab, In SYstemic sclerosis (DAISY).

Methods: DAISY includes a 52-week double-blind, placebo-controlled treatment period, a 52-week open-label active treatment period, and a 12-week safety follow-up period. The patient population includes a planned 306 adults with limited or diffuse cutaneous active SSc who satisfied American College of Rheumatology/European Alliance of Associations for Rheumatology 2013 SSc criteria. Use of standard immunosuppressants, …

Ephb2 Receptor Promotes Dermal Fibrosis In Systemic Sclerosis, Erika S A Egal, Severin Donald Kamdem, Masaaki Yoshigi, Ching-Chu Yang, Sarah Pellizzari, Ernest M Kameni, My N Helms, Shervin Assassi, Mark Henkemeyer, Tracy M Frech, Patrice N Mimche

Faculty, Staff and Student Publications

Objective: Erythropoietin-producing hepatocellular (Eph)/Ephrin cell-cell signaling is emerging as a key player in tissue fibrogenesis. The aim of this study was to test the hypothesis that the receptor tyrosine kinase EphB2 mediates dermal fibrosis in systemic sclerosis (SSc).

Methods: We assessed normal and SSc human skin biopsies for EphB2 expression. The in vivo role of EphB2 in skin fibrosis was investigated by subjecting EphB2-knockout mice to both bleomycin-induced and tight skin (Tsk1/+) genetic mouse models of skin fibrosis. EphB2 kinase-dead and overactive point mutant mice were used to evaluate the role of EphB2 forward signaling in bleomycin-induced dermal fibrosis. In …

From Disorder Comes Function: Regulation Of Small Gtpase Function By Intrinsically Disordered Lipidated Membrane Anchor, Chase M Hutchins, Alemayehu A Gorfe

Faculty, Staff and Student Publications

The intrinsically disordered, lipid-modified membrane anchor of small GTPases is emerging as a critical modulator of function through its ability to sort lipids in a conformation-dependent manner. We reviewed recent computational and experimental studies that have begun to shed light on the sequence-ensemble-function relationship in this unique class of lipidated intrinsically disordered regions (LIDRs).

Electrical Stimulation Of The Dorsal Motor Nucleus Of The Vagus In Male Mice Can Regulate Inflammation Without Affecting The Heart Rate, Aidan Falvey, Santhoshi P Palandira, Sangeeta S Chavan, Michael Brines, Robert Dantzer, Kevin J Tracey, Valentin A Pavlov

Faculty, Staff and Student Publications

Background: The vagus nerve plays an important role in neuroimmune interactions and in the regulation of inflammation. A major source of efferent vagus nerve fibers that contribute to the regulation of inflammation is the brainstem dorsal motor nucleus of the vagus (DMN), as recently shown using optogenetics. In contrast to optogenetics, electrical neuromodulation has broad therapeutic implications. However, the anti-inflammatory effectiveness of electrical stimulation of the DMN (eDMNS) and the possible heart rate (HR) alterations associated with this approach have not been investigated. Here, we examined the effects of eDMNS on HR and cytokine levels in mice administered with lipopolysaccharide …

Collaborative Filtering For The Imputation Of Patient Reported Outcomes, Eric Ababio Anyimadu, Clifton David Fuller, Xinhua Zhang, G Elisabeta Marai, Guadalupe Canahuate

Faculty, Staff and Student Publications

This study addresses the prevalent issue of missing data in patient-reported outcome datasets, particularly focusing on head and neck cancer patient symptom ratings sourced from the MD Anderson Symptom Inventory. Given that many data mining and machine learning algorithms necessitate complete datasets, the accurate imputation of missing data as an initial step becomes crucial. In this study we propose, for the first time, the use of collaborative filtering for imputing missing head and neck cancer patient symptom ratings. Two configurations of collaborative filtering, namely patient-based and symptom-based, leverage known ratings to infer the missing ones. Additionally, this study compares the …

Targeting Adenosine A2b Receptor Promotes Penile Rehabilitation Of Refractory Erectile Dysfunction, Yang Xiong, Feng Qin, Shanzun Wei, Xingliang Yang, Jun Li, Changjing Wu, Fuxun Zhang, Jiuhong Yuan

Faculty, Staff and Student Publications

The mechanisms of adenosine and specific adenosine receptor subtypes in promoting penile rehabilitation remain unclear. Single‐cell RNA sequencing of human corpus cavernosum,  adenosine deaminase (ADA) and adenosine receptors knock‐out mice (ADA−/−, A1−/−, A2a−/−, A2b−/−, and A3−/−), and primary corpus cavernosum smooth muscle cells are used to determine receptor subtypes responsible for adenosine‐induced erection. Three rat models are established to characterize refractory erectile dysfunction (ED): age‐related ED, bilateral cavernous nerve crush related ED (BCNC), and diabetes mellitus‐induced ED. In single‐cell RNA sequencing data, the corpus cavernosum of ED patients show a decrease in adenosine A1, A2a and A2b receptors. In vivo, …

Candida Albicans Natural Diversity: A Resource To Dissect Fungal Commensalism And Pathogenesis, Elena Lindemann-Perez, J Christian Perez

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Candida albicans is a ubiquitous fungus of humans. It is not only a component of the oral and intestinal microbiota of most healthy adults but also a major cause of mucosal disorders and life-threatening disseminated infections. Until recently, research on the biology and pathogenesis of the fungus was largely based on a single clinical isolate. We review investigations that have started to dissect a diverse set of C. albicans strains. Using different approaches to leverage the species' phenotypic and/or genetic diversity, these studies illuminate the wide range of interactions between fungus and host. While connecting genetic variants to phenotypes of …

Comparative Toxicological Assessment Of 2 Bisphenols Using A Systems Approach: Evaluation Of The Behavioral And Transcriptomic Responses Of Danio Rerio To Bisphenol A And Tetrabromobisphenol A, Michael G Morash, Morgan W Kirzinger, John C Achenbach, Ananda B Venkatachalam, Jessica Nixon, Susanne Penny, Joëlle Pinsonnault Cooper, Deborah E Ratzlaff, Cindy L A Woodland, Lee D Ellis

Faculty, Staff and Student Publications

The zebrafish (Danio rerio) is becoming a critical component of new approach methods (NAMs) in chemical risk assessment. As a whole organism in vitro NAM, the zebrafish model offers significant advantages over individual cell-line testing, including toxicokinetic and toxicodynamic competencies. A transcriptomic approach not only allows for insight into mechanism of action for both apical endpoints and unobservable adverse outcomes, but also changes in gene expression induced by lower, environmentally relevant concentrations. In this study, we used a larval zebrafish model to assess the behavioral and transcriptomic alterations caused by subphenotypic concentrations of 2 chemicals with the same structural backbone, …

A Qualitative Narrative Study Of Rescue And Recovery Workers Responding To The Terrorist Bombing Of Oklahoma City's Murrah Building, E Whitney Pollio, Jennifer Wang, Edward Randle, David E Pollio, Carol S North

Faculty, Staff and Student Publications

OBJECTIVE: Much of disaster mental health research uses quantitative methods, focusing on numerical prevalence, services, and outcomes.

METHODS: Qualitative methods can provide more detailed, rich, and spontaneous insights into personal disaster experiences, yielding important insights beyond deductive methods. This large-scale qualitative narrative study examined experiences of 181 Oklahoma City bombing rescue/recovery workers.

RESULTS: Thematic narrative content of the bombing experience arose from personal accounts of the bomb blast by rescue/recovery workers proceeding chronologically from initial awareness and deployment to harrowing onsite search and rescue/recovery missions to the aftermath with reflections on the bombing.

CONCLUSIONS: Beyond disaster recovery/rescue worker stories published …

Patient-Derived Organoids As Therapy Screening Platforms In Cancer Patients, Danial Khorsandi, Jia-Wei Yang, Samuel Foster, Safoora Khosravi, Negar Hosseinzadeh Kouchehbaghi, Fahimeh Zarei, Yun Bin Lee, Farhana Runa, Ankit Gangrade, Leon Voskanian, Darbaz Adnan, Yangzhi Zhu, Zhaohui Wang, Vadim Jucaud, Mehmet Remzi Dokmeci, Xiling Shen, Faraz Bishehsari, Jonathan A Kelber, Ali Khademhosseini, Natan Roberto De Barros

Faculty, Staff and Student Publications

Patient-derived organoids (PDOs) developed ex vivo and in vitro are increasingly used for therapeutic screening. They provide a more physiologically relevant model for drug discovery and development compared to traditional cell lines. However, several challenges remain to be addressed to fully realize the potential of PDOs in therapeutic screening. This paper summarizes recent advancements in PDO development and the enhancement of PDO culture models. This is achieved by leveraging materials engineering and microfabrication technologies, including organs-on-a-chip and droplet microfluidics. Additionally, this work discusses the application of PDOs in therapy screening to meet diverse requirements and overcome bottlenecks in cancer treatment. …

Social Determinants Of Long-Term Opioid Use Following Total Knee Arthroplasty, Katherine Hadlandsmyth, Brian C Lund, Yubo Gao, Andrea L Strayer, Heather Davila, Leslie R M Hausmann, Susanne Schmidt, Paula K Shireman, Michael A Jacobs, Michael J Mader, Robert A Tessler, Carly A Duncan, Daniel E Hall, Mary Vaughan Sarrazin

Faculty, Staff and Student Publications

Total knee arthroplasty (TKA) risks persistent pain and long-term opioid use (LTO). The role of social determinants of health (SDoH) in LTO is not well established. We hypothesized that SDoH would be associated with postsurgical LTO after controlling for relevant demographic and clinical variables. This study utilized data from the Veterans Affairs Surgical Quality Improvement Program, VA Corporate Data Warehouse, and Centers for Medicare and Medicaid Services, including Veterans aged ≥ 65 who underwent elective TKA between 2013 and 2019 with no postsurgical complications or history of significant opioid use. LTO was defined as > 90 days of opioid use beginning …

Care Fragmentation, Social Determinants Of Health, And Postoperative Mortality In Older Veterans, Carly A Duncan, Michael A Jacobs, Yubo Gao, Michael Mader, Susanne Schmidt, Heather Davila, Katherine Hadlandsmyth, Paula K Shireman, Leslie R M Hausmann, Robert A Tessler, Andrea Strayer, Mary Vaughan Sarrazin, Daniel E Hall

Faculty, Staff and Student Publications

Introduction: Veterans Affairs Surgical Quality Improvement Program (VASQIP) benchmarking algorithms helped the Veterans Health Administration (VHA) reduce postoperative mortality. Despite calls to consider social risk factors, these algorithms do not adjust for social determinants of health (SDoH) or account for services fragmented between the VHA and the private sector. This investigation examines how the addition of SDoH change model performance and quantifies associations between SDoH and 30-d postoperative mortality.

Methods: VASQIP (2013-2019) cohort study in patients ≥65 y old with 2-30-d inpatient stays. VASQIP was linked to other VHA and Medicare/Medicaid data. 30-d postoperative mortality was examined using multivariable logistic …

Molecular Pathways And Cellular Subsets Associated With Adverse Clinical Outcomes In Overlapping Immune-Related Myocarditis And Myositis, Bilal A Siddiqui, Nicolas L Palaskas, Sreyashi Basu, Yibo Dai, Zhong He, Shalini S Yadav, James P Allison, Rahul A Sheth, Sudhakar Tummala, Maximilian Buja, Meenakshi B Bhattacharjee, Cezar Iliescu, Anishia Rawther-Karedath, Anita Deswal, Linghua Wang, Padmanee Sharma, Sumit K Subudhi

Faculty, Staff and Student Publications

Immune checkpoint therapies (ICT) can induce life-threatening immune-related adverse events, including myocarditis and myositis, which are rare but often concurrent. The molecular pathways and immune subsets underlying these toxicities remain poorly understood. To address this need, we performed single-cell RNA sequencing of heart and skeletal muscle biopsies obtained from living patients with cancers treated with ICTs and admitted to the hospital with myocarditis and/or myositis (overlapping myocarditis plus myositis, n = 10; myocarditis-only, n = 1) or ICT-exposed patients ruled out for toxicity utilized as controls (n = 9). All biopsies were obtained within 96 hours of clinical presentation. Analyses …

Combination Of Dasatinib And Venetoclax In Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia, Elias Jabbour, Fadi G Haddad, Koji Sasaki, Bing Z Carter, Yesid Alvarado, Cedric Nasnas, Lewis Nasr, Lucia Masarova, Naval Daver, Naveen Pemmaraju, Nicholas J Short, Jeffrey Skinner, Tapan Kadia, Gautam Borthakur, Guillermo Garcia-Manero, Farhad Ravandi, Ghayas C Issa, Michael Andreeff, Hagop Kantarjian

Faculty, Staff and Student Publications

Background: The dual inhibition of the BCR::ABL1 tyrosine kinase and BCL-2 could potentially deepen the response rates of chronic myeloid leukemia in chronic phase (CML-CP). This study evaluated the safety and efficacy of the combination of dasatinib and venetoclax.

Methods: In this phase 2 trial, patients with CML-CP or accelerated phase (clonal evolution) received dasatinib 50 mg/day for three courses; venetoclax was added in course 4 for 3 years. The initial venetoclax dose was 200 mg/day continuously but reduced later to 200 mg/day for 14 days, and to 100 mg/day for 7 days per course once a molecular response (MR)4.5 …

Trends In Outcomes After Upfront Autologous Transplant For Multiple Myeloma Over Three Decades, Oren Pasvolsky, Curtis Marcoux, Jianliang Dai, Denái R Milton, Mark R Tanner, Naureen Syed, Qaiser Bashir, Samer Srour, Neeraj Saini, Paul Lin, Jeremy Ramdial, Yago Nieto, Guilin Tang, Yosra Aljawai, Hans C Lee, Mahmoud R Gaballa, Krina K Patel, Partow Kebriaei, Sheeba K Thomas, Robert Z Orlowski, Elizabeth J Shpall, Richard E Champlin, Muzaffar H Qazilbash

Faculty, Staff and Student Publications

Upfront autologous stem cell transplantation (auto-SCT) remains standard of care for eligible patients with newly diagnosed multiple myeloma (NDMM), although recently its role has been questioned. The aim of the study was to evaluate trends in patient characteristics, treatment, and outcomes of NDMM who underwent upfront auto-SCT over three decades. We conducted a single-center retrospective analysis of patients with NDMM who underwent upfront auto-SCT at MD Anderson Cancer Center between 1988 to 2021. Primary end points were progression-free survival (PFS) and overall survival (OS). Patients were grouped by the year of auto-SCT: 1988-2000 (n = 249), 2001-2005 (n = 373), …

Why Do Patients With Cancer Die?, Adrienne Boire, Katy Burke, Thomas R Cox, Theresa Guise, Mariam Jamal-Hanjani, Tobias Janowitz, Rosandra Kaplan, Rebecca Lee, Charles Swanton, Matthew G Vander Heiden, Erik Sahai

Faculty, Staff and Student Publications

Cancer is a major cause of global mortality, both in affluent countries and increasingly in developing nations. Many patients with cancer experience reduced life expectancy and have metastatic disease at the time of death. However, the more precise causes of mortality and patient deterioration before death remain poorly understood. This scarcity of information, particularly the lack of mechanistic insights, presents a challenge for the development of novel treatment strategies to improve the quality of, and potentially extend, life for patients with late-stage cancer. In addition, earlier deployment of existing strategies to prolong quality of life is highly desirable. In this …

Pbi-05204, A Supercritical Co2 Extract Of Nerium Oleander, Suppresses Glioblastoma Stem Cells By Inhibiting Grp78 And Inducing Programmed Necroptotic Cell, Sharmistha Chakraborty, Daoyan Wei, Megan Tran, Frederick F Lang, Robert A Newman, Peiying Yang

Faculty, Staff and Student Publications

Successful treatment of glioblastoma multiforme (GBM), an aggressive form of primary brain neoplasm, mandates the need to develop new therapeutic strategies. In this study, we investigated the potential of PBI-05204 in targeting GBM stem cells (GSCs) and the underlying mechanisms. Treatment with PBI-05204 significantly reduced both the number and size of tumor spheres derived from patient-derived GSCs (GBM9, GSC28 and TS543), and suppressed the tumorigenesis of GBM9 xenografts. Moreover, PBI-05204 treatment led to a significant decrease in the expression of CD44 and NANOG, crucial markers of progenitor stem cells, in GBM9 and GSC28 GSCs. This treatment also down-regulated GRP78 expression …

Inhibition Of Lysine Acetyltransferase Kat6 In Er+Her2− Metastatic Breast Cancer: A Phase 1 Trial, Toru Mukohara, Yeon Hee Park, David Sommerhalder, Kan Yonemori, Erika Hamilton, Sung-Bae Kim, Jee Hyun Kim, Hiroji Iwata, Toshinari Yamashita, Rachel M Layman, Monica Mita, Timothy Clay, Yee Soo Chae, Catherine Oakman, Fengting Yan, Gun Min Kim, Seock-Ah Im, Geoffrey J Lindeman, Hope S Rugo, Marlon Liyanage, Michelle Saul, Christophe Le Corre, Athanasia Skoura, Li Liu, Meng Li, Patricia M Lorusso

Faculty, Staff and Student Publications

Inhibition of histone lysine acetyltransferases (KATs) KAT6A and KAT6B has shown antitumor activity in estrogen receptor-positive (ER+) breast cancer preclinical models. PF-07248144 is a selective catalytic inhibitor of KAT6A and KAT6B. In the present study, we report the safety, pharmacokinetics (PK), pharmacodynamics, efficacy and biomarker results from the first-in-human, phase 1 dose escalation and dose expansion study (n = 107) of PF-07248144 monotherapy and fulvestrant combination in heavily pretreated ER+ human epidermal growth factor receptor-negative (HER2−) metastatic breast cancer (mBC). The primary objectives of assessing the safety and tolerability and determining the recommended dose for expansion of PF-07248144, as …

Metronidazole May Display Anti-Inflammatory Features In Periodontitis Treatment: A Scoping Review, Lina J Suárez, Roger M Arce, Cristiane Gonçalves, Camila Pinheiro Furquim, Nidia Castro Dos Santos, Belén Retamal-Valdes, Magda Feres

Faculty, Staff and Student Publications

Aim: Metronidazole (MTZ) is an antimicrobial agent used to treat anaerobic infections. It has been hypothesized that MTZ may also have anti-inflammatory properties, but the evidence is limited and has not been previously reviewed. Thus, this scoping review aimed to answer the following question: "What is the evidence supporting anti-inflammatory properties of metronidazole that are not mediated by its antimicrobial effects?"

Methods: A scoping review was conducted according to the PRISMA-ScR statement. Five databases were searched up to January 2023 for studies evaluating the anti-inflammatory properties of MTZ used as monotherapy for treating infectious and inflammatory diseases.

Results: A total …