Digital Commons Network^™

Targeting Mirnas And Other Non-Coding Rnas As A Therapeutic Approach: An Update, Emine Bayraktar, Recep Bayraktar, Hulya Oztatlici, Gabriel Lopez-Berestein, Paola Amero, Cristian Rodriguez-Aguayo

Faculty, Staff and Student Publications

Since the discovery of the first microRNAs (miRNAs, miRs), the understanding of miRNA biology has expanded substantially. miRNAs are involved and described as master regulators of the major hallmarks of cancer, including cell differentiation, proliferation, survival, the cell cycle, invasion, and metastasis. Experimental data indicate that cancer phenotypes can be modified by targeting miRNA expression, and because miRNAs act as tumor suppressors or oncogenes (oncomiRs), they have emerged as attractive tools and, more importantly, as a new class of targets for drug development in cancer therapeutics. With the use of miRNA mimics or molecules targeting miRNAs (i.e., small-molecule inhibitors such …

Targeting Of Epigenetic Co-Dependencies Enhances Anti-Aml Efficacy Of Menin Inhibitor In Aml With Mll1-R Or Mutant Npm1, Warren Fiskus, Christopher P Mill, Christine Birdwell, John A Davis, Kaberi Das, Steffen Boettcher, Tapan M Kadia, Courtney D Dinardo, Koichi Takahashi, Sanam Loghavi, Michael J Soth, Tim Heffernan, Gerard M Mcgeehan, Xinjia Ruan, Xiaoping Su, Christopher R Vakoc, Naval Daver, Kapil N Bhalla

Faculty, Staff and Student Publications

Monotherapy with Menin inhibitor (MI), e.g., SNDX-5613, induces clinical remissions in patients with relapsed/refractory AML harboring MLL1-r or mtNPM1, but most patients either fail to respond or eventually relapse. Utilizing single-cell RNA-Seq, ChiP-Seq, ATAC-Seq, RNA-Seq, RPPA, and mass cytometry (CyTOF) analyses, present pre-clinical studies elucidate gene-expression correlates of MI efficacy in AML cells harboring MLL1-r or mtNPM1. Notably, MI-mediated genome-wide, concordant, log2 fold-perturbations in ATAC-Seq and RNA-Seq peaks were observed at the loci of MLL-FP target genes, with upregulation of mRNAs associated with AML differentiation. MI treatment also reduced the number of AML cells expressing the stem/progenitor cell signature. A …

Characterization Of Recurrence Patterns And Outcomes Of Medulloblastoma In Adults: The University Of Texas Md Anderson Cancer Center Experience, Timothy A Gregory, Maximilian Mastall, Heather Lin, Kenneth R Hess, Ying Yuan, Manuela Martin-Bejarano Garcia, Gregory N Fuller, Kristin D Alfaro, Maria K Gule-Monroe, Jason T Huse, Soumen Khatua, Ganesh Rao, David I Sandberg, Jeffrey S Wefel, Debra N Yeboa, Arnold C Paulino, Susan L Mcgovern, Wafik Zaky, Anita Mahajan, Dima Suki, Shiao-Pei Weathers, Rebecca A Harrison, John F De Groot, Vinay K Puduvalli, Marta Penas-Prado, Nazanin K Majd

Faculty, Staff and Student Publications

BACKGROUND: Medulloblastoma in adults is rare and treatment decisions are largely driven from pediatric literature. We sought to characterize recurrent medulloblastoma in adults.

METHODS: From a single-institution dataset of 200 adult patients diagnosed with medulloblastoma during 1978-2017, those with recurrence were analyzed for clinical features, treatment, and outcome.

RESULTS: Of the 200 patients, 82 (41%) with median age of 29 years (18-59) had recurrence after a median follow-up time of 8.4 years (95% CI = 7.1, 10.3). Of these, 30 (37%) were standard-risk, 31 (38%) were high-risk, and 21 (26%) had unknown-risk diseases at the time of initial diagnosis. Forty-eight …

Cancer Neuroscience: State Of The Field, Emerging Directions, Frank Winkler, Humsa S Venkatesh, Moran Amit, Tracy Batchelor, Ihsan Ekin Demir, Benjamin Deneen, David H Gutmann, Shawn Hervey-Jumper, Thomas Kuner, Donald Mabbott, Michael Platten, Asya Rolls, Erica K Sloan, Timothy C Wang, Wolfgang Wick, Varun Venkataramani, Michelle Monje

Faculty, Staff and Student Publications

The nervous system governs both ontogeny and oncology. Regulating organogenesis during development, maintaining homeostasis, and promoting plasticity throughout life, the nervous system plays parallel roles in the regulation of cancers. Foundational discoveries have elucidated direct paracrine and electrochemical communication between neurons and cancer cells, as well as indirect interactions through neural effects on the immune system and stromal cells in the tumor microenvironment in a wide range of malignancies. Nervous system-cancer interactions can regulate oncogenesis, growth, invasion and metastatic spread, treatment resistance, stimulation of tumor-promoting inflammation, and impairment of anti-cancer immunity. Progress in cancer neuroscience may create an important new …

One Population, Multiple Lifestyles: Commensalism And Pathogenesis In The Human Mycobiome, Diana M Proctor, Rebecca A Drummond, Michail S Lionakis, Julia A Segre

Faculty, Staff and Student Publications

Candida auris and Candida albicans can result in invasive fungal diseases. And yet, these species can stably and asymptomatically colonize human skin and gastrointestinal tracts. To consider these disparate microbial lifestyles, we first review factors shown to influence the underlying microbiome. Structured by the damage response framework, we then consider the molecular mechanisms deployed by C. albicans to switch between commensal and pathogenic lifestyles. Next, we explore this framework with C. auris to highlight how host physiology, immunity, and/or antibiotic receipt are associated with progression from colonization to infection. While treatment with antibiotics increases the risk an individual will succumb …

Development Of A Corticosteroid-Immunosuppressed Mouse Model To Study The Pathogenesis And Therapy Of Influenza-Associated Pulmonary Aspergillosis, Sebastian Wurster, Jezreel Pantaleón García, Nathaniel D Albert, Ying Jiang, Keerthi Bhoda, Vikram V Kulkarni, Yongxing Wang, Thomas J Walsh, Scott Evans, Dimitrios P Kontoyiannis

Faculty, Staff and Student Publications

Influenza-associated pulmonary aspergillosis (IAPA) is a feared complication in patients with influenza tracheobronchitis, especially those receiving corticosteroids. Herein, we established a novel IAPA mouse model with low-inoculum Aspergillus infection and compared outcomes in mice with and without cortisone acetate (CA) immunosuppression. CA was an independent predictor of increased morbidity/mortality in mice with IAPA. Early antifungal treatment with liposomal amphotericin B was pivotal to improve IAPA outcomes in CA-immunosuppressed mice, even after prior antiviral therapy with oseltamivir. In summary, our model recapitulates key clinical features of IAPA and provides a robust preclinical platform to study the pathogenesis and treatment of IAPA.

Physio-Psycho-Social Interaction Mechanism In Dyadic Health Of Young And Middle-Aged Stroke Survivors And Their Spousal Caregivers: A Longitudinal Observational Study Protocol, Dandan Xiang, Zhen-Xiang Zhang, Song Ge, Wen Na Wang, Bei-Lei Lin, Su-Yan Chen, Er-Feng Guo, Peng-Bo Zhang, Zhi-Wei Liu, Hui Li, Yong-Xia Mei

Faculty, Staff and Student Publications

Introduction: In recent years, stroke has become more common among young people. Stroke not only has a profound impact on patients' health but also incurs stress and health threats to their caregivers, especially spousal caregivers. Moreover, the health of stroke survivors and their caregivers is interdependent. To our knowledge, no study has explored dyadic health of young and middle-aged stroke survivors and their spousal caregivers from physiological, psychological and social perspectives. Therefore, this proposed study aims to explore the mechanism of how physiological, psychological and social factors affect dyadic health of young and middle-aged stroke survivors and their spousal caregivers. …

Quantitative Proteomic Screening Uncovers Candidate Diagnostic And Monitoring Serum Biomarkers Of Ankylosing Spondylitis, Mark Hwang, Shervin Assassi, Jim Zheng, Jessica Castillo, Reyna Chavez, Kamala Vanarsa, Chandra Mohan, John Reveille

Faculty, Staff and Student Publications

BACKGROUND: We sought to discover serum biomarkers of ankylosing spondylitis (AS) for diagnosis and monitoring disease activity.

METHODS: We studied biologic-treatment-naïve AS and healthy control (HC) patients' sera. Eighty samples matched by age, gender, and race (1:1:1 ratio) for AS patients with active disease, inactive disease, and HC were analyzed with SOMAscan™, an aptamer-based discovery platform. T-tests tests were performed for high/low-disease activity AS patients versus HCs (diagnosis) and high versus low disease activity (Monitoring) in a 2:1 and 1:1 ratio, respectively, to identify differentially expressed proteins (DEPs). We used the Cytoscape Molecular Complex Detection (MCODE) plugin to find clusters …

Risk Of Early Death In Adolescents And Young Adults With Cancer: A Population-Based Study, Amy M Berkman, Clark R Andersen, Michelle A T Hildebrandt, J A Livingston, Adam L Green, Vidya Puthenpura, Susan K Peterson, Joel Milam, Kimberly A Miller, David R Freyer, Michael E Roth

Faculty, Staff and Student Publications

BACKGROUND: Advancements in treatment and supportive care have led to improved survival for adolescents and young adults (AYAs) with cancer; however, a subset of those diagnosed remain at risk for early death (within 2 months of diagnosis). Factors that place AYAs at increased risk of early death have not been well studied.

METHODS: The Surveillance, Epidemiology, and End Results registry was used to assess risk of early death in AYAs with hematologic malignancies, central nervous system tumors, and solid tumors. Associations between age at diagnosis, sex, race, ethnicity, socioeconomic status, insurance status, rurality, and early death were assessed.

RESULTS: A …

Effect Of Angiotensin-Converting Enzyme Inhibitor And Angiotensin Receptor Blocker Initiation On Organ Support-Free Days In Patients Hospitalized With Covid-19: A Randomized Clinical Trial, Patrick R Lawler, Lennie P G Derde, Frank L Van De Veerdonk, Bryan J Mcverry, David T Huang, Lindsay R Berry, Elizabeth Lorenzi, Roland Van Kimmenade, Frank Gommans, Muthiah Vaduganathan, David E Leaf, Rebecca M Baron, Edy Y Kim, Claudia Frankfurter, Slava Epelman, Yvonne Kwan, Richard Grieve, Stephen O'Neill, Zia Sadique, Michael Puskarich, John C Marshall, Alisa M Higgins, Paul R Mouncey, Kathryn M Rowan, Farah Al-Beidh, Djillali Annane, Yaseen M Arabi, Carly Au, Abi Beane, Wilma Van Bentum-Puijk, Marc J M Bonten, Charlotte A Bradbury, Frank M Brunkhorst, Aidan Burrell, Adrian Buzgau, Meredith Buxton, Maurizio Cecconi, Allen C Cheng, Matthew Cove, Michelle A Detry, Lise J Estcourt, Justin Ezekowitz, Mark Fitzgerald, David Gattas, Lucas C Godoy, Herman Goossens, Rashan Haniffa, David A Harrison, Thomas Hills, Christopher M Horvat, Nao Ichihara, Francois Lamontagne, Kelsey M Linstrum, Daniel F Mcauley, Anna Mcglothlin, Shay P Mcguinness, Zoe Mcquilten, Srinivas Murthy, Alistair D Nichol, David R J Owen, Rachael L Parke, Jane C Parker, Katrina M Pollock, Luis Felipe Reyes, Hiroki Saito, Marlene S Santos, Christina T Saunders, Christopher W Seymour, Manu Shankar-Hari, Vanessa Singh, Alexis F Turgeon, Anne M Turner, Ryan Zarychanski, Cameron Green, Roger J Lewis, Derek C Angus, Scott Berry, Anthony C Gordon, Colin J Mcarthur, Steve A Webb

Faculty, Staff and Student Publications

IMPORTANCE: Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19.

OBJECTIVE: To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19.

DESIGN, SETTING, AND PARTICIPANTS: In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non-critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022).

INTERVENTIONS: Patients were randomized to receive open-label initiation of an ACE inhibitor …

Upper Age Limits For Us Male Human Papillomavirus Vaccination For Oropharyngeal Cancer Prevention: A Microsimulation-Based Modeling Study, Rebecca Landy, Gregory Haber, Barry I Graubard, Nicole G Campos, Stephen Sy, Jane J Kim, Emily A Burger, Li C Cheung, Hormuzd A Katki, Maura L Gillison, Anil K Chaturvedi

Faculty, Staff and Student Publications

BACKGROUND: Human papillomavirus (HVP)-positive oropharyngeal cancer is the most common HPV-associated cancer in the United States. The age at acquisition of oral HPV infections that cause oropharyngeal cancer (causal infections) is unknown; consequently, the benefit of vaccination of US men aged 27-45 years remains uncertain.

METHODS: We developed a microsimulation-based, individual-level, state-transition model of oral HPV16 and HPV16-positive oropharyngeal cancer among heterosexual US men aged 15-84 years, calibrated to population-level data. We estimated the benefit of vaccination of men aged 27-45 years for prevention of oropharyngeal cancer, accounting for direct- and indirect effects (ie, herd effects) of male and female …

Molecular Mechanisms Of Ferroptosis And Updates Of Ferroptosis Studies In Cancers And Leukemia, Hiroki Akiyama, Bing Z Carter, Michael Andreeff, Jo Ishizawa

Faculty, Staff and Student Publications

Ferroptosis is a mode of cell death regulated by iron-dependent lipid peroxidation. Growing evidence suggests ferroptosis induction as a novel anti-cancer modality that could potentially overcome therapy resistance in cancers. The molecular mechanisms involved in the regulation of ferroptosis are complex and highly dependent on context. Therefore, a comprehensive understanding of its execution and protection machinery in each tumor type is necessary for the implementation of this unique cell death mode to target individual cancers. Since most of the current evidence for ferroptosis regulation mechanisms is based on solid cancer studies, the knowledge of ferroptosis with regard to leukemia is …

A Phase 1/2 Study Of Lenalidomide And Obinutuzumab With Chop For Newly Diagnosed Dlbcl, Hua-Jay J Cherng, Stefan K Alig, Yasuhiro Oki, Loretta J Nastoupil, Luis Fayad, Sattva S Neelapu, Francesco Turturro, Fredrick Hagemeister, Alexander F M Craig, Charles W Macaulay, Maria Alma Rodriguez, Hun Ju Lee, Timothy J Mcdonnell, Christopher R Flowers, Francisco Vega, Michael R Green, Lei Feng, David M Kurtz, Ash A Alizadeh, R Eric Davis, Jason R Westin

Faculty, Staff and Student Publications

Diffuse large B-cell lymphoma (DLBCL) can be cured with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP); however, one-third of patients experience refractory or relapsed disease. Studies comparing R-CHOP with modified regimens replacing R with obinutuzumab (O) or adding lenalidomide (L) did not result in improved outcomes; however, L and O together may enhance natural killer-cell mediated antibody-dependent cellular toxicity when paired with CHOP. Here, we report on a phase 1b/2 study of 53 patients with newly diagnosed DLBCL who received 6 cycles of LO-CHOP. The end of treatment overall and complete response rates of the 50 evaluable patients were 98% …

Hypoxia Increases Atx Expression By Histone Crotonylation In A Hif-2Α-Dependent Manner, Mengxia Qu, Yang Long, Yuqin Wang, Nan Yin, Xiaotian Zhang, Junjie Zhang

Faculty, Staff and Student Publications

Autotaxin (ATX), the key enzyme that generates lysophosphatidic acid (LPA) from lysophosphatidylcholine (LPC), is involved in tumorigenesis through the ATX-LPA axis and is regarded as a valuable target in tumor therapy. Hypoxia is a major feature of solid tumors and contributes to tumor development with striking alterations in the gene expression profile. Here, we show that hypoxia induces ATX expression in a hypoxia-inducible factor (HIF) 2α-dependent fashion in human colon cancer SW480 cells. HIF-2α is directly bound to specific hypoxia response elements (HREs) in the ATX promoter. Under hypoxic conditions, knockout or inhibition of ATX suppressed the migration of SW480 …

Structural Foundations Of Potassium Selectivity In Channelrhodopsins, Sukyeong Lee, Sang Bum Lee, Nuri Sung, Wendy W Xu, Changsoo Chang, Hyun-Eui Kim, Andre Catic, Francis T F Tsai

Faculty, Staff and Student Publications

Mitochondria are critical to cellular and organismal health. To prevent damage, mitochondria have evolved protein quality control machines to survey and maintain the mitochondrial proteome. SKD3, also known as CLPB, is a ring-forming, ATP-fueled protein disaggregase essential for preserving mitochondrial integrity and structure. SKD3 deficiency causes 3-methylglutaconic aciduria type VII (MGCA7) and early death in infants, while mutations in the ATPase domain impair protein disaggregation with the observed loss-of-function correlating with disease severity. How mutations in the non-catalytic N-domain cause disease is unknown. Here, we show that the disease-associated N-domain mutation, Y272C, forms an intramolecular disulfide bond with Cys267 and …

Fruit And Vegetable Intake And Home Nutrition Environment Among Low-Income Minority Households With Elementary-Aged Children, Brittni Naylor Metoyer, Ru-Jye Chuang, Minjae Lee, Christine Markham, Eric L Brown, Maha Almohamad, Jayna M Dave, Shreela V Sharma

Faculty, Staff and Student Publications

Racial/ethnic and socioeconomic differences were shown to have an influence on child fruit and vegetable intake. This study examined the associations between parent and child fruit and vegetable intake and the home nutrition environment among Hispanic/Latino and African American families. Through a cross-sectional study design, self-reported surveys (

Mapping The Metabolic Reprogramming Induced By Sodium-Glucose Cotransporter 2 Inhibition, Aviram Kogot-Levin, Yael Riahi, Ifat Abramovich, Ofri Mosenzon, Bella Agranovich, Liat Kadosh, Rachel Ben-Haroush Schyr, Doron Kleiman, Liad Hinden, Erol Cerasi, Danny Ben-Zvi, Ernesto Bernal-Mizrachi, Joseph Tam, Eyal Gottlieb, Gil Leibowitz

Faculty, Staff and Student Publications

Diabetes is associated with increased risk for kidney disease, heart failure, and mortality. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) prevent these adverse outcomes; however, the mechanisms involved are not clear. We generated a roadmap of the metabolic alterations that occur in different organs in diabetes and in response to SGLT2i. In vivo metabolic labeling with 13C-glucose in normoglycemic and diabetic mice treated with or without dapagliflozin, followed by metabolomics and metabolic flux analyses, showed that, in diabetes, glycolysis and glucose oxidation are impaired in the kidney, liver, and heart. Treatment with dapagliflozin failed to rescue glycolysis. SGLT2 inhibition increased glucose oxidation …

Influence Of Trpm4 Rs8104571 Genotype On Intracranial Pressure And Outcomes In African Americans With Traumatic Brain Injury, Joseph D Krocker, Madeline E Cotton, Jacob B Schriner, Baron K Osborn, Michael M Talanker, Yao-Wei W Wang, Charles S Cox, Charles E Wade

Faculty, Staff and Student Publications

The TRPM4 gene codes for a membrane ion channel subunit related to inflammation in the central nervous system. Recent investigation has identified an association between TRPM4 single nucleotide polymorphisms (SNPs) rs8104571 and rs150391806 and increased intracranial (ICP) pressure following traumatic brain injury (TBI). We assessed the influence of these genotypes on clinical outcomes and ICP in TBI patients. We included 292 trauma patients with TBI. DNA extraction and real-time PCR were used for TRPM4 rs8104571 and rs150391806 allele discrimination. Five participants were determined to have the rs8104571 homozygous variant genotype, and 20 participants were identified as heterozygotes; 24 of these …

Acute Traumatic Dural Arteriovenous Fistula Of The Superior Sagittal Sinus: Illustrative Case, Mitchell L Pryce, K H Carlos Chung, Hussein A Zeineddine, Bryden H Dawes

Faculty, Staff and Student Publications

Background: Dural arteriovenous fistulas (dAVFs) are aberrant vascular communications between meningeal arteries and venous sinuses or cortical veins. dAVF pathogenesis is incompletely understood; however, formation likely occurs as a result of angioneogensis.

Observations: A 78-year-old man presented after trauma with basal and cortical subarachnoid hemorrhage (SAH). Computed tomography revealed a parietal bone fracture overlying the superior sagittal sinus (SSS). Catheter angiography performed within 24 hours of the injury demonstrated an SSS dAVF supplied by the middle meningeal artery, adjacent to the fracture.

Lessons: The authors present the case of an acute traumatic dAVF adjacent to a calvarial fracture. In this …

Neuronal Birthdate Reveals Topography In A Vestibular Brainstem Circuit For Gaze Stabilization, Dena Goldblatt, Stephanie Huang, Marie R Greaney, Kyla R Hamling, Venkatakaushik Voleti, Citlali Perez-Campos, Kripa B Patel, Wenze Li, Elizabeth M C Hillman, Martha W Bagnall, David Schoppik

Faculty, Staff and Student Publications

Across the nervous system, neurons with similar attributes are topographically organized. This topography reflects developmental pressures. Oddly, vestibular (balance) nuclei are thought to be disorganized. By measuring activity in birthdated neurons, we revealed a functional map within the central vestibular projection nucleus that stabilizes gaze in the larval zebrafish. We first discovered that both somatic position and stimulus selectivity follow projection neuron birthdate. Next, with electron microscopy and loss-of-function assays, we found that patterns of peripheral innervation to projection neurons were similarly organized by birthdate. Finally, birthdate revealed spatial patterns of axonal arborization and synapse formation to projection neuron outputs. …

Targeting The Mevalonate Pathway Suppresses Arid1a-Inactivated Cancers By Promoting Pyroptosis, Wei Zhou, Heng Liu, Zhe Yuan, Joseph Zundell, Martina Towers, Jianhuang Lin, Simona Lombardi, Hao Nie, Brennah Murphy, Tyler Yang, Chen Wang, Liping Liao, Aaron R Goldman, Toshitha Kannan, Andrew V Kossenkov, Ronny Drapkin, Luis J Montaner, Daniel T Claiborne, Nan Zhang, Shuai Wu, Rugang Zhang

Faculty, Staff and Student Publications

ARID1A, encoding a subunit of the SWI/SNF complex, is mutated in ∼50% of clear cell ovarian carcinoma (OCCC) cases. Here we show that inhibition of the mevalonate pathway synergizes with immune checkpoint blockade (ICB) by driving inflammasome-regulated immunomodulating pyroptosis in ARID1A-inactivated OCCCs. SWI/SNF inactivation downregulates the rate-limiting enzymes in the mevalonate pathway such as HMGCR and HMGCS1, which creates a dependence on the residual activity of the pathway in ARID1A-inactivated cells. Inhibitors of the mevalonate pathway such as simvastatin suppresses the growth of ARID1A mutant, but not wild-type, OCCCs. In addition, simvastatin synergizes with anti-PD-L1 antibody in a genetic OCCC …

Metabolic Dysregulation Impairs Lymphocyte Function During Severe Sars-Cov-2 Infection, Sanjeev Gurshaney, Anamaria Morales-Alvarez, Kevin Ezhakunnel, Andrew Manalo, Thien-Huong Huynh, Jun-Ichi Abe, Nhat-Tu Le, Daniela Weiskopf, Alessandro Sette, Daniel S Lupu, Stephen J Gardell, Hung Nguyen

Faculty, Staff and Student Publications

Cellular metabolic dysregulation is a consequence of SARS-CoV-2 infection that is a key determinant of disease severity. However, how metabolic perturbations influence immunological function during COVID-19 remains unclear. Here, using a combination of high-dimensional flow cytometry, cutting-edge single-cell metabolomics, and re-analysis of single-cell transcriptomic data, we demonstrate a global hypoxia-linked metabolic switch from fatty acid oxidation and mitochondrial respiration towards anaerobic, glucose-dependent metabolism in CD8+Tc, NKT, and epithelial cells. Consequently, we found that a strong dysregulation in immunometabolism was tied to increased cellular exhaustion, attenuated effector function, and impaired memory differentiation. Pharmacological inhibition of mitophagy with mdivi-1 reduced excess glucose …

Progressive Muscle Relaxation Exercises In Patients With Covid-19: Systematic Review And Meta-Analysis, Abubeker Alebachew Seid, Ahmed Adem Mohammed, Aragaw Asfaw Hasen

Faculty, Staff and Student Publications

BACKGROUND: Patients with COVID-19 will experience high levels of anxiety and depression and poor levels of sleep and quality of life (QoL) due to isolation treatment and uncertain outcomes. Progressive muscle relaxation (PMR) exercises show promising treatment effects on mental health and sleep problems and overall QoL in COVID-19 patients. This study aimed to evaluate the efficacy and safety of PMR exercises in patients with COVID-19.

METHODS: Both experimental and non-experimental studies related to PMR and COVID-19 were systematically searched in the PubMed, Cochrane Library, PEDro and HINARI databases for studies published from the occurrence of the pandemic to December …

Distribution Of Serum Uric Acid Concentration And Its Association With Lipid Profiles: A Single-Center Retrospective Study In Children Aged 3 To 12 Years With Adenoid And Tonsillar Hypertrophy, Jiating Yu, Xin Liu, Honglei Ji, Yawei Zhang, Hanqiang Zhan, Ziyin Zhang, Jianguo Wen, Zhimin Wang

Faculty, Staff and Student Publications

BACKGROUND: Presently, there is no consensus regarding the optimal serum uric acid (SUA) concentration for pediatric patients. Adenoid and tonsillar hypertrophy is considered to be closely associated with pediatric metabolic syndrome and cardiovascular risk and is a common condition in children admitted to the hospital. Therefore, we aimed to evaluate the relationship between SUA and dyslipidemia and propose a reference range for SUA concentration that is associated with a healthy lipid profile in hospitalized children with adenoid and tonsillar hypertrophy.

METHODS: Preoperative data from 4922 children admitted for elective adenoidectomy and/or tonsillectomy surgery due to adenoid and tonsillar hypertrophy were …

Prmt3-Mediated Arginine Methylation Of Igf2bp1 Promotes Oxaliplatin Resistance In Liver Cancer, Yunxing Shi, Yi Niu, Yichuan Yuan, Kai Li, Chengrui Zhong, Zhiyu Qiu, Keren Li, Zhu Lin, Zhiwen Yang, Dinglan Zuo, Jiliang Qiu, Wei He, Chenwei Wang, Yadi Liao, Guocan Wang, Yunfei Yuan, Binkui Li

Faculty, Staff and Student Publications

Although oxaliplatin-based chemotherapy has been effective in the treatment of hepatocellular carcinoma (HCC), primary or acquired resistance to oxaliplatin remains a major challenge in the clinic. Through functional screening using CRISPR/Cas9 activation library, transcriptomic profiling of clinical samples, and functional validation in vitro and in vivo, we identify PRMT3 as a key driver of oxaliplatin resistance. Mechanistically, PRMT3-mediated oxaliplatin-resistance is in part dependent on the methylation of IGF2BP1 at R452, which is critical for the function of IGF2BP1 in stabilizing the mRNA of HEG1, an effector of PRMT3-IGF2BP1 axis. Also, PRMT3 overexpression may serve as a biomarker for oxaliplatin resistance …

A Dynamic Risk Model For Multitype Recurrent Events, Alokananda Ghosh, Wenyaw Chan, Naji Younes, Barry R Davis

Faculty, Staff and Student Publications

Recurrent events can occur more than once in the same individual; such events may be of different types, known as multitype recurrent events. They are very common in longitudinal studies. Often there is a terminating event, after which no further events can occur. The risk of any event, including terminating events such as death or cure, is typically affected by prior events. We propose a flexible joint multitype recurrent-events model that explicitly provides estimates of the change in risk for each event due to subject characteristics, including number and type of prior events and the absolute risk for every event …

A Distinct Pattern Of Growth And Rac1 Signaling In Melanoma Brain Metastasis Cells, Ioana Stejerean-Todoran, Phyllis A Gimotty, Andrea Watters, Patricia Brafford, Clemens Krepler, Tetiana Godok, Haiyin Li, Zuriñe Bonilla Del Rio, Anke Zieseniss, Dörthe M Katschinski, Sinem M Sertel, Silvio O Rizzoli, Bradley Garman, Katherine L Nathanson, Xiaowei Xu, Qing Chen, Jack H Oswald, Michal Lotem, Gordon B Mills, Michael A Davies, Michael P Schön, Ivan Bogeski, Meenhard Herlyn, Adina Vultur

Faculty, Staff and Student Publications

Background: Melanoma, the deadliest of skin cancers, has a high propensity to form brain metastases that are associated with a markedly worsened prognosis. In spite of recent therapeutic advances, melanoma brain lesions remain a clinical challenge, biomarkers predicting brain dissemination are not clear and differences with other metastatic sites are poorly understood.

Methods: We examined a genetically diverse panel of human-derived melanoma brain metastasis (MBM) and extracranial cell lines using targeted sequencing, a Reverse Phase Protein Array, protein expression analyses, and functional studies in vitro and in vivo.

Results: Brain-specific genetic alterations were not detected; however, MBM cells in vitro …

Mutation-Agnostic Detection Of Colorectal Cancer Using Liquid Biopsy-Based Methylation-Specific Signatures, Mohamed A Gouda, Dzifa Y Duose, Morten Lapin, Stephanie Zalles, Helen J Huang, Yuanxin Xi, Xiaofeng Zheng, Amira I Aldesoky, Alshimaa M Alhanafy, Mohamed A Shehata, Jing Wang, Scott Kopetz, Funda Meric-Bernstam, Ignacio I Wistuba, Rajyalakshmi Luthra, Filip Janku

Faculty, Staff and Student Publications

Detection of methylation patterns in circulating tumor DNA (ctDNA) can offer a novel approach for cancer diagnostics given the unique signature for each tumor type. We developed a next-generation sequencing (NGS)-based assay targeting 32 CpG sites to detect colorectal cancer-specific ctDNA. NGS was performed on bisulfite-converted libraries and status dichotomization was done using median methylation ratios at all targets. We included plasma samples from patients with metastatic colorectal (n = 20) and non-colorectal cancers (n = 8); and healthy volunteers (n = 4). Median methylation ratio was higher in colorectal cancer compared with non-colorectal cancers (P = .001) and normal …

An Expedited Strategy For Accurate And Timely Integrated Molecular Diagnosis Of Gliomas, Timothy A Gregory, Garret L Williford, Jacob M Maronge, Kristin Alfaro, Gregory N Fuller, John De Groot, Vinay K Puduvalli, Leomar Y Ballester, Nazanin K Majd

Faculty, Staff and Student Publications

No abstract provided.

Brain Metastases From Biliary Tract Cancer: Case Series And Clinicogenomic Analysis, Grace N Dodoo, Brian De, Sunyoung S Lee, Joseph Abi Jaoude, Jean-Nicolas Vauthey, Ching-Wei D Tzeng, Hop S Tran Cao, Kalman A Katlowitz, Jacob J Mandel, Thomas H Beckham, Bruce D Minsky, Grace L Smith, Emma B Holliday, Albert C Koong, Prajnan Das, Cullen M Taniguchi, Milind Javle, Eugene J Koay, Ethan B Ludmir

Faculty, Staff and Student Publications

BACKGROUND: Limited data from small series have suggested that brain metastases from biliary tract cancers (BrM-BTC) affect ≤2% of patients with BTC. We sought to review our experience with patients with BrM-BTC and to identify associations of tumor-related molecular alterations with outcomes.

MATERIALS AND METHODS: A retrospective review of patients with BTC seen at a tertiary referral center from 2005 to 2021 was performed; patients with BrM-BTC were identified, and clinical and molecular data were collected.

RESULTS: Twenty-one of 823 patients with BTC (2.6%) developed BrM. For patients with BrM-BTC, median follow-up time was 27.9 months after primary BTC diagnosis …