Digital Commons Network^™

Prevalence, Incidence, And Clearance Of Human Papillomavirus Types Covered By Current Vaccines In Men With Human Immunodeficiency Virus In The Sun Study, Pragna Patel, Tim Bush, Lois Conley, Elizabeth R Unger, Teresa M Darragh, Keith Henry, Gerome Escota, John T Brooks, Erna Milunka Kojic

2020-Current year OA Pubs

BACKGROUND: High-risk anal human papillomavirus (HPV) infection is prevalent among men living with human immunodeficiency virus (HIV); the association between 9-valent (9v) high-risk HPV (HR-HPV) vaccine types and abnormal cytology has not been well characterized.

METHODS: We followed a prospective cohort study of persons with HIV at 7 HIV clinics in 4 US cities from March 2004 through June 2012. Annually, providers collected separate anal swabs for HPV detection and cytopathologic examination. Among men, we examined prevalence, incidence, and clearance of 9v HR-HPV vaccine types, compared with other HR types, and associations with abnormal cytology to assess potential vaccine impact. …

Phenotypic Profiling In Subjects Heterozygous For 1 Of 2 Rare Variants In The Hypophosphatasia Gene (Alpl), Daniel R Tilden, Jonathan H Sheehan, John H Newman, Jens Meiler, John A Capra, Andrea Ramirez, Jill Simmons, Kathryn Dahir

Open Access Publications

CONTEXT: Hypophosphatasia (HPP) is a syndrome marked by low serum alkaline phosphatase (AlkP) activity as well as musculoskeletal and/or dental disease. While the majority of subjects with HPP carry a pathogenic variant in the

METHODS: Through BioVU, a DNA biobank that pairs individuals' genetic information with their de-identified medical records, we identified subjects with 2 rare variants with distinct reported clinical phenotypes (p.D294A and p.T273M). We then performed a manual review of these subjects' de-identified medical records along with computational modeling of protein structure to construct a genetic, biochemical and clinical phenotype for each subject and variant.

RESULTS: Twenty subjects …

Exploiting The Circuit Breaker Cancer Evolution Model In Human Clear Cell Renal Cell Carcinoma, James J Hsieh, Emily H Cheng

Open Access Publications

The incessant interactions between susceptible humans and their respective macro/microenvironments registered throughout their lifetime result in the ultimate manifestation of individual cancers. With the average lifespan exceeding 50 years of age in humans since the beginning of 20

Development Of A Single-Stranded Dna-Binding Protein Fluorescent Fusion Toolbox, Katarzyna Dubiel, Camille Henry, Lisanne M. Spenkelink, Alexander G. Kozlov, Elizabeth A. Wood, Slobodan Jergic, Nicholas E. Dixon, Antoine M. Van Oijen, Michael M. Cox, Timothy M. Lohman, Steven J. Sandler, James L. Keck

Open Access Publications

Bacterial single-stranded DNA-binding proteins (SSBs) bind single-stranded DNA and help to recruit heterologous proteins to their sites of action. SSBs perform these essential functions through a modular structural architecture: the N-terminal domain comprises a DNA binding/tetramerization element whereas the C-terminus forms an intrinsically disordered linker (IDL) capped by a protein-interacting SSB-Ct motif. Here we examine the activities of SSB-IDL fusion proteins in which fluorescent domains are inserted within the IDL of Escherichia coli SSB. The SSB-IDL fusions maintain DNA and protein binding activities in vitro, although cooperative DNA binding is impaired. In contrast, an SSB variant with a fluorescent protein …

Pet Radiopharmaceuticals For Imaging Chemotherapy-Induced Cardiotoxicity, Jothilingam Sivapackiam, Monica Sharma, Thomas H Schindler, Vijay Sharma

Open Access Publications

PURPOSE OF REVIEW: Currently, cardiotoxicity is monitored through echocardiography or multigated acquisition scanning and is defined as 10% or higher LVEF reduction. The latter stage may represent irreversible myocardium injury and limits modification of therapeutic paradigms at earliest stages. To stratify patients for anthracycline-related heart failure, highly sensitive and molecularly specific probes capable of interrogating cardiac damage at the subcellular levels have been sought.

RECENT FINDINGS: PET tracers may provide noninvasive assessment of earliest changes within myocardium. These tracers are at nascent stages of development and belong primarily to (a) mitochondrial potential-targeted and (b) general ROS (reactive oxygen species)-targeted radiotracers. …

25-Hydroxycholesterol Amplifies Microglial Il-1Β Production In An Apoe Isoform-Dependent Manner, Man Ying Wong, Michael Lewis, James J Doherty, Yang Shi, Anil G Cashikar, Anna Amelianchik, Svitlana Tymchuk, Patrick M Sullivan, Mingxing Qian, Douglas F Covey, Gregory A Petsko, David M Holtzman, Steven M Paul, Wenjie Luo

2020-Current year OA Pubs

BACKGROUND: Genome-wide association studies of Alzheimer's disease (AD) have implicated pathways related to lipid homeostasis and innate immunity in AD pathophysiology. However, the exact cellular and chemical mediators of neuroinflammation in AD remain poorly understood. The oxysterol 25-hydroxycholesterol (25-HC) is an important immunomodulator produced by peripheral macrophages with wide-ranging effects on cell signaling and innate immunity. Cholesterol 25-hydroxylase (CH25H), the enzyme responsible for 25-HC production, has also been found to be one of the disease-associated microglial (DAM) genes that are upregulated in the brain of AD and AD transgenic mouse models.

METHODS: We used real-time PCR and immunoblotting to examine …

Cumulative Exposure To Long Working Hours And Occurrence Of Ischemic Heart Disease: Evidence From The Constances Cohort At Inception, Marc Fadel, Jian Li, Grace Sembajwe, Diana Gagliardi, Fernando Pico, Anna Ozguler, Bradley A Evanoff, Michel Baer, Akizumi Tsutsumi, Sergio Iavicoli, Annette Leclerc, Yves Roquelaure, Johannes Siegrist, Alexis Descatha

Open Access Publications

Background Long-working hours (LWH) are a probable risk factor for ischemic heart diseases (IHD); however, no previous study has considered duration of exposure to LWH when addressing this topic. We aimed to determine the association between cumulative exposure to LWH and IHD while accounting for relevant confounders. Methods and Results In this retrospective study, we included all baseline participants from the French population-based cohort CONSTANCES. Part-time employees and those who reported a cardiac event in the 5 years before LWH exposure were excluded. From self-administered questionnaires and clinical examinations, we obtained participants' age, sex, body mass index, occupational status, smoking …

Oligomerization Of The Vesicular Stomatitis Virus Phosphoprotein Is Dispensable For Mrna Synthesis But Facilitates Rna Replication, Louis-Marie Bloyet, Benjamin Morin, Vesna Brusic, Erica Gardner, Robin A. Ross, Tegy Vadakkan, Tomas Kirchhausen, Sean P. J. Whelan

Open Access Publications

Nonsegmented negative-strand (NNS) RNA viruses possess a ribonucleoprotein template in which the genomic RNA is sequestered within a homopolymer of nucleocapsid protein (N). The viral RNA-dependent RNA polymerase (RdRP) resides within an approximately 250-kDa large protein (L), along with unconventional mRNA capping enzymes: a GDP:polyribonucleotidyltransferase (PRNT) and a dual-specificity mRNA cap methylase (MT). To gain access to the N-RNA template and orchestrate the L

A Survey-Based Analysis Of The Academic Job Market, Jason D. Fernandes, Sarvenaz Sarabipour, Christopher T. Smith, Natalie M. Niemi, Nafisa M. Jadavji, Ariangela J. Kozik, Alex S. Holehouse, Vikas Pejaver, Orsolya Symmons, Alexandre W. Bisson Filho, Amanda Haage

Open Access Publications

Many postdoctoral researchers apply for faculty positions knowing relatively little about the hiring process or what is needed to secure a job offer. To address this lack of knowledge about the hiring process we conducted a survey of applicants for faculty positions: the survey ran between May 2018 and May 2019, and received 317 responses. We analyzed the responses to explore the interplay between various scholarly metrics and hiring outcomes. We concluded that, above a certain threshold, the benchmarks traditionally used to measure research success - including funding, number of publications or journals published in - were unable to completely …

The Neurons That Mistook A Hat For A Face, Michael J. Arcaro, Carlos Ponce, Margaret Livingstone

Open Access Publications

Despite evidence that context promotes the visual recognition of objects, decades of research have led to the pervasive notion that the object processing pathway in primate cortex consists of multiple areas that each process the intrinsic features of a few particular categories (e.g. faces, bodies, hands, objects, and scenes). Here we report that such category-selective neurons do not in fact code individual categories in isolation but are also sensitive to object relationships that reflect statistical regularities of the experienced environment. We show by direct neuronal recording that face-selective neurons respond not just to an image of a face, but also …

Implications Of New Understandings Of Gliomas In Children And Adults With Nf1: Report Of A Consensus Conference, Roger J Packer, David H Gutmann, Et Al.

2020-Current year OA Pubs

Gliomas are the most common primary central nervous system tumors occurring in children and adults with neurofibromatosis type 1 (NF1). Over the past decade, discoveries of the molecular basis of low-grade gliomas (LGGs) have led to new approaches for diagnosis and treatments. However, these new understandings have not been fully applied to the management of NF1-associated gliomas. A consensus panel consisting of experts in NF1 and gliomas was convened to review the current molecular knowledge of NF1-associated low-grade "transformed" and high-grade gliomas; insights gained from mouse models of NF1-LGGs; challenges in diagnosing and treating older patients with NF1-associated gliomas; and …

Cd56 Regulates Human Nk Cell Cytotoxicity Through Pyk2, Justin T. Gunesch, Amera L. Dixon, Tasneem A.M. Ebrahim, Melissa M. Berrien-Elliott, Swetha Tatineni, Tejas Kumar, Everardo Hegewisch-Solloa, Todd A. Fehniger, Emily M. Mace

Open Access Publications

Human natural killer (NK) cells are defined as CD56

Multidimensional Imaging Of Liver Injury Repair In Mice Reveals Fundamental Role Of The Ductular Reaction, Kenji Kamimoto, Yasuhiro Nakano, Kota Kaneko, Atsushi Miyajima, Tohru Itoh

Open Access Publications

Upon severe and/or chronic liver injury, ectopic emergence and expansion of atypical biliary epithelial-like cells in the liver parenchyma, known as the ductular reaction, is typically induced and implicated in organ regeneration. Although this phenomenon has long been postulated to represent activation of facultative liver stem/progenitor cells that give rise to new hepatocytes, recent lineage-tracing analyses have challenged this notion, thereby leaving the pro-regenerative role of the ductular reaction enigmatic. Here, we show that the expanded and remodelled intrahepatic biliary epithelia in the ductular reaction constituted functional and complementary bile-excreting conduit systems in injured parenchyma where hepatocyte bile canalicular networks …

Ccdc61/Vfl3 Is A Paralog Of Sas6 And Promotes Ciliary Functions, Takashi Ochi, Huawen Lin, Susan K Dutcher, Et Al.

2020-Current year OA Pubs

Centrioles are cylindrical assemblies whose peripheral microtubule array displays a 9-fold rotational symmetry that is established by the scaffolding protein SAS6. Centriole symmetry can be broken by centriole-associated structures, such as the striated fibers in Chlamydomonas that are important for ciliary function. The conserved protein CCDC61/VFL3 is involved in this process, but its exact role is unclear. Here, we show that CCDC61 is a paralog of SAS6. Crystal structures of CCDC61 demonstrate that it contains two homodimerization interfaces that are similar to those found in SAS6, but result in the formation of linear filaments rather than rings. Furthermore, we show …

Stage-Specific Requirement For Eomes In Mature Nk Cell Homeostasis And Cytotoxicity, Julia A Wagner, Pamela Wong, Timothy Schappe, Melissa M Berrien-Elliott, Celia Cubitt, Natalia Jaeger, Madeline Lee, Cassie R Keppel, Nancy D Marin, Jennifer A Foltz, Lynne Marsala, Carly C Neal, Ryan P Sullivan, Stephanie E Schneider, Molly P Keppel, Nermina Saucier, Megan A Cooper, Todd A Fehniger

Open Access Publications

Natural killer (NK) cells are cytotoxic innate lymphoid cells (ILCs) that mediate antiviral and antitumor responses and require the transcriptional regulator Eomesodermin (Eomes) for early development. However, the role of Eomes and its molecular program in mature NK cell biology is unclear. To address this, we develop a tamoxifen-inducible, type-1-ILC-specific (Ncr1-targeted) cre mouse and combine this with Eomes-floxed mice. Eomes deletion after normal NK cell ontogeny results in a rapid loss of NK cells (but not ILC1s), with a particularly profound effect on penultimately mature stage III NK cells. Mechanisms responsible for stage III reduction include increased apoptosis and impaired …

Covid-19 Clinical Trials: A Primer For The Cardiovascular And Cardio-Oncology Communities, Bonnie Ky, Douglas L Mann

Open Access Publications

The coronavirus disease-2019 (COVID-19) pandemic has resulted in a proliferation of clinical trials designed to slow the spread of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Many therapeutic agents that are being used to treat patients with COVID-19 are repurposed treatments for influenza, Ebola, or for malaria that were developed decades ago and are unlikely to be familiar to the cardiovascular and cardio-oncology communities. Here, we provide a foundation for cardiovascular and cardio-oncology physicians on the front line providing care to patients with COVID-19, so that they may better understand the emerging cardiovascular epidemiology and the biological rationale for the clinical trials …

Efficacy Of Bezlotoxumab In Participants Receiving Metronidazole, Vancomycin, Or Fidaxomicin For Treatment Of Clostridioides (Clostridium) Difficile Infection, Erik R. Dubberke, Dale N. Gerding, Ciarán P. Kelly, Kevin W. Garey, Galia Rahav, Audrey Mosley, Robert Tipping, Mary Beth Dorr

Open Access Publications

Background: In phase 3 MODIFY I/II trials, bezlotoxumab significantly reduced recurrence of

Methods: In MODIFY I/II (NCT01241552/NCT01513239), participants received a single infusion of bezlotoxumab (10 mg/kg) or placebo during anti-CDI treatment. Using pooled data from MODIFY I/II, initial clinical cure (ICC) and rCDI were assessed in metronidazole-, vancomycin-, and fidaxomicin-treated subgroups.

Results: Of 1554 participants in MODIFY I/II, 753 (48.5%) received metronidazole, 745 (47.9%) vancomycin, and 56 (3.6%) fidaxomicin. Fewer participants receiving metronidazole had a prior CDI episode in the previous 6 months (12.9%) or ≥1 risk factor for rCDI (66.0%) vs participants receiving vancomycin (41.2% and 83.6%, respectively) and …

The Wrinkling Of Time: Aging, Inflammation, Oxidative Stress, And The Circadian Clock In Neurodegeneration, Brian V Lananna, Erik S Musiek

2020-Current year OA Pubs

A substantial body of research now implicates the circadian clock in the regulation of an array of diverse biological processes including glial function, metabolism, peripheral immune responses, and redox homeostasis. Sleep abnormalities and other forms of circadian disruption are common symptoms of aging and neurodegeneration. Circadian clock disruption may also influence the aging processes and the pathogenesis of neurodegenerative diseases. The specific mechanisms governing the interaction between circadian systems, aging, and the immune system are still being uncovered. Here, we review the evidence supporting a bidirectional relationship between aging and the circadian system. Further, we explore the hypothesis that age-related …

Growth Velocity In Children With Environmental Enteric Dysfunction Is Associated With Specific Bacterial And Viral Taxa Of The Gastrointestinal Tract In Malawian Children, Chandni Desai, Scott A. Handley, Rachel Rodgers, Cynthia Rodriguez, Maria I. Ordiz, Mark J. Manary, Lori R. Holtz

Open Access Publications

Environmental enteric dysfunction (EED) is characterized by diffuse villous atrophy of the small bowel. EED is strongly associated with stunting, a major public health problem linked to increased childhood morbidity and mortality. EED and subsequent stunting of linear growth are surmised to have microbial origins. To interrogate this relationship, we defined the comprehensive virome (eukaryotic virus and bacteriophage) and bacterial microbiome of a longitudinal cohort of rural Malawian children with extensive metadata and intestinal permeability testing at each time point. We found thirty bacterial taxa differentially associated with linear growth. We detected many eukaryotic viruses. Neither the total number of …

Potent, Specific Mepicides For Treatment Of Zoonotic Staphylococci, Rachel L. Edwards, Isabel Heueck, Soon Goo Lee, Ishaan T. Shah, Justin J. Miller, Andrew J. Jezewski, Marwa O. Mikati, Xu Wang, Robert C. Brothers, Kenneth M. Heidel, Damon M. Osbourn, Carey-Ann D. Burnham, Sophie Alvarez, Stephanie A. Fritz, Cynthia S. Dowd, Joseph M. Jez, Audrey R. Odom John

Open Access Publications

Coagulase-positive staphylococci, which frequently colonize the mucosal surfaces of animals, also cause a spectrum of opportunistic infections including skin and soft tissue infections, urinary tract infections, pneumonia, and bacteremia. However, recent advances in bacterial identification have revealed that these common veterinary pathogens are in fact zoonoses that cause serious infections in human patients. The global spread of multidrug-resistant zoonotic staphylococci, in particular the emergence of methicillin-resistant organisms, is now a serious threat to both animal and human welfare. Accordingly, new therapeutic targets that can be exploited to combat staphylococcal infections are urgently needed. Enzymes of the methylerythritol phosphate pathway (MEP) …

Repository Corticotropin Injection For Active Rheumatoid Arthritis Despite Aggressive Treatment: A Randomized Controlled Withdrawal Trial., Roy Fleischmann, Daniel E Furst, Erin Connolly-Strong, Jingyu Liu, Julie Zhu, Richard Brasington

Open Access Publications

INTRODUCTION: The objective of this study was to assess efficacy and safety of repository corticotropin injection (RCI) in subjects with active rheumatoid arthritis (RA) despite treatment with a corticosteroid and one or two disease-modifying antirheumatic drugs (DMARDs).

METHODS: All subjects received open-label RCI (80 U) twice weekly for 12 weeks (part 1); only those with low disease activity [LDA; i.e., Disease Activity Score 28 joint count and erythrocyte sedimentation rate (DAS28-ESR) < 3.2] were randomly assigned to receive either RCI (80 U) or placebo twice weekly during the 12-week double-blind period (part 2). The primary efficacy endpoint was the proportion of subjects who achieved LDA at week 12. Secondary efficacy endpoints included proportions of subjects who maintained LDA during weeks 12 through 24 and achieved Clinical Disease Activity Index (CDAI) ≤ 10 at weeks 12 and 24. Safety was assessed via adverse event reports.

RESULTS: Of the 259 enrolled subjects, 235 completed part 1; 154 subjects (n = 77 each for RCI and placebo) entered part 2, and 127 (RCI, n = 71; …

Tfeb Is A Master Regulator Of Tumor-Associated Macrophages In Breast Cancer, Yong Li, Johnie Hodge, Qing Liu, Junfeng Wang, Yuzhen Wang, Trent D Evans, Diego Altomare, Yongzhong Yao, E. Angela Murphy, Babak Razani, Daping Fan

2020-Current year OA Pubs

BACKGROUND: Tumor-associated macrophages (TAMs) play key roles in the development of many malignant solid tumors including breast cancer. They are educated in the tumor microenvironment (TME) to promote tumor growth, metastasis, and therapy resistance. However, the phenotype of TAMs is elusive and how to regulate them for therapeutic purpose remains unclear; therefore, TAM-targeting therapies have not yet achieved clinical success. The purposes of this study were to examine the role of transcription factor EB (TFEB) in regulating TAM gene expression and function and to determine if TFEB activation can halt breast tumor development.

METHODS: Microarrays were used to analyze the …

Epigenomic Programming In Early Fetal Brain Development, Luolan Li, Ting Wang, Et Al

2020-Current year OA Pubs

No abstract provided.

Conformational Distributions Of Isolated Myosin Motor Domains Encode Their Mechanochemical Properties, Justin R. Porter, Artur Meller, Maxwell I. Zimmerman, Michael J. Greenberg, Gregory R. Bowman

Open Access Publications

Myosin motor domains perform an extraordinary diversity of biological functions despite sharing a common mechanochemical cycle. Motors are adapted to their function, in part, by tuning the thermodynamics and kinetics of steps in this cycle. However, it remains unclear how sequence encodes these differences, since biochemically distinct motors often have nearly indistinguishable crystal structures. We hypothesized that sequences produce distinct biochemical phenotypes by modulating the relative probabilities of an ensemble of conformations primed for different functional roles. To test this hypothesis, we modeled the distribution of conformations for 12 myosin motor domains by building Markov state models (MSMs) from an …

Plasmodium Falciparum Translational Machinery Condones Polyadenosine Repeats, Slavica Pavlovic Djuranovic, Jessey Erath, Ryan J. Andrews, Peter O. Bayguinov, Joyce J. Chung, Douglas L. Chalker, James A.J. Fitzpatrick, Walter N. Moss, Pawel Szczesny, Sergej Djuranovic

Open Access Publications

No abstract provided.

In Utero Exposure To Transient Ischemia-Hypoxemia Promotes Long-Term Neurodevelopmental Abnormalities In Male Rat Offspring, Arvind Palanisamy, Tusar Giri, Jia Jiang, Annie Bice, James D Quirk, Sara B Conyers, Susan E Maloney, Nandini Raghuraman, Adam Q Bauer, Joel R Garbow, David F Wozniak

Open Access Publications

The impact of transient ischemic-hypoxemic insults on the developing fetal brain is poorly understood despite evidence suggesting an association with neurodevelopmental disorders such as schizophrenia and autism. To address this, we designed an aberrant uterine hypercontractility paradigm with oxytocin to better assess the consequences of acute, but transient, placental ischemia-hypoxemia in term pregnant rats. Using MRI, we confirmed that oxytocin-induced aberrant uterine hypercontractility substantially compromised uteroplacental perfusion. This was supported by the observation of oxidative stress and increased lactate concentration in the fetal brain. Genes related to oxidative stress pathways were significantly upregulated in male, but not female, offspring 1 …

Quantitative Analysis Of Transcription Factor Binding And Expression Using Calling Cards Reporter Arrays, Jiayue Liu, Christian A. Shively, Robi D. Mitra

Open Access Publications

We report a tool, Calling Cards Reporter Arrays (CCRA), that measures transcription factor (TF) binding and the consequences on gene expression for hundreds of synthetic promoters in yeast. Using Cbf1p and MAX, we demonstrate that the CCRA method is able to detect small changes in binding free energy with a sensitivity comparable to in vitro methods, enabling the measurement of energy landscapes in vivo. We then demonstrate the quantitative analysis of cooperative interactions by measuring Cbf1p binding at synthetic promoters with multiple sites. We find that the cooperativity between Cbf1p dimers varies sinusoidally with a period of 10.65 bp and …

Sex-Specific Impact Of Patterns Of Imageable Tumor Growth On Survival Of Primary Glioblastoma Patients, Paula Whitmire, Joshua B Rubin, Et Al

Open Access Publications

BACKGROUND: Sex is recognized as a significant determinant of outcome among glioblastoma patients, but the relative prognostic importance of glioblastoma features has not been thoroughly explored for sex differences.

METHODS: Combining multi-modal MR images, biomathematical models, and patient clinical information, this investigation assesses which pretreatment variables have a sex-specific impact on the survival of glioblastoma patients (299 males and 195 females).

RESULTS: Among males, tumor (T1Gd) radius was a predictor of overall survival (HR = 1.027, p = 0.044). Among females, higher tumor cell net invasion rate was a significant detriment to overall survival (HR = 1.011, p < 0.001). Female extreme survivors had significantly smaller tumors (T1Gd) (p = 0.010 t-test), but tumor size was not correlated with female overall survival (p = 0.955 CPH). Both male and female extreme survivors had significantly lower tumor cell net proliferation rates than other patients (M p = 0.004, F p = 0.001, t-test).

CONCLUSION: Despite …

Site-Specific Siderocalin Binding To Ferric And Ferric-Free Enterobactin As Revealed By Mass Spectrometry, Chunyang Guo, Lindsey K Steinberg, Ming Cheng, Jong Hee Song, Jeffrey P Henderson, Michael L Gross

Open Access Publications

Both host and pathogen competitively manipulate coordination environments during bacterial infections. Human cells release the innate immune protein siderocalin (Scn, also known as lipocalin-2/Lcn2, neutrophil gelatinase-associated lipocalin/NGAL) that can inhibit bacterial growth by sequestering iron in a ferric complex with enterobactin (Ent), the ubiquitous

A Randomized Controlled Phase Iii Study Of Vb-111 Combined With Bevacizumab Vs Bevacizumab Monotherapy In Patients With Recurrent Glioblastoma (Globe), Timothy F Cloughesy, Andrew Brenner, John F De Groot, Nicholas A Butowski, Leor Zach, Jian L Campian, Benjamin M Ellingson, Laurence S Freedman, Yael C Cohen, Noa Lowenton-Spier, Tamar Rachmilewitz Minei, Shifra Fain Shmueli, Globe Study Investigators, Patrick Y Wen

2020-Current year OA Pubs

BACKGROUND: Ofranergene obadenovec (VB-111) is an anticancer viral therapy that demonstrated in a phase II study a survival benefit for patients with recurrent glioblastoma (rGBM) who were primed with VB-111 monotherapy that was continued after progression with concomitant bevacizumab.

METHODS: This pivotal phase III randomized, controlled trial compared the efficacy and safety of upfront combination of VB-111 and bevacizumab versus bevacizumab monotherapy. Patients were randomized 1:1 to receive VB-111 1013 viral particles every 8 weeks in combination with bevacizumab 10 mg/kg every 2 weeks (combination arm) or bevacizumab monotherapy (control arm). The primary endpoint was overall survival (OS), and secondary …