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Dominik Pfister, Nicolás Gonzalo Núñez, Roser Pinyol et al. · 2021 · Nature
Abstract Hepatocellular carcinoma (HCC) can have viral or non-viral causes 1–5 . Non-alcoholic steatohepatitis (NASH) is an important driver of HCC. Immunotherapy has been approved for treating HCC, but biomarker-based stratification of patients for optimal response to therapy is an unmet need 6,7 . Here we report the progressive accumulation of exhausted, unconventionally activated CD8 + PD1 + T cells in NASH-affected livers. In preclinical models of NASH-induced HCC, therapeutic immunotherapy targeted at programmed death-1 (PD1) expanded activated CD8 + PD1 + T cells within tumours but did n
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Laura Evgin, Amanda L. Huff, Phonphimon Wongthida et al. · 2020 · Nature Communications
The application of adoptive T cell therapies, including those using chimeric antigen receptor (CAR)-modified T cells, to solid tumors requires combinatorial strategies to overcome immune suppression associated with the tumor microenvironment. Here we test whether the inflammatory nature of oncolytic viruses and their ability to remodel the tumor microenvironment may help to recruit and potentiate the functionality of CAR T cells. Contrary to our hypothesis, VSVmIFNβ infection is associated with attrition of murine EGFRvIII CAR T cells in a B16EGFRvIII model, despite inducing a robust proinflam
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Kaori Kuramitsu, Deanna Sverdlov, Susan B. Liu et al. · 2013 · American Journal Of Pathology
Failure of fibrotic liver to regenerate after resection limits therapeutic options and increases demand for liver transplantation, representing a significant clinical problem. The mechanism underlying regenerative failure in fibrosis is…
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Thomas R. Lerner, Cristiane de Souza Carvalho‐Wodarz, Urška Repnik et al. · 2016 · Journal of Clinical Investigation
In extrapulmonary tuberculosis, the most common site of infection is within the lymphatic system, and there is growing recognition that lymphatic endothelial cells (LECs) are involved in immune function. Here, we identified LECs, which…
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Lauren A. Wise, Edward Ruiz-Narváez, Julie R. Palmer et al. · 2012 · American Journal of Epidemiology
Rates of uterine leiomyomata (UL) are 2-3 times higher in African Americans than in European Americans. It is unclear whether inherited factors explain the ethnic disparity. To investigate the presence of risk alleles for UL that are…
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Michael A. Castello, John D. Jeppson, Salvador Soriano · 2014 · BMC Neurology
BACKGROUND: High-profile Phase 3 clinical trials of bapineuzumab and solanezumab, antibodies targeted at amyloid-beta (Aβ) removal, have failed to meet their primary endpoints. Neither drug improves clinical outcomes in patients with late onset AD, joining a long list of unsuccessful attempts to treat AD with anti-amyloid therapies. DISCUSSION: These therapies are based on the assumption that Aβ accumulation is the primary pathogenic trigger of AD. Current evidence suggests that Aβ may actually accumulate as part of an adaptive response to long-term chronic brain stress stimuli that would make
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Darryl Falzarano, David Safronetz, Joseph Prescott et al. · 2015 · Emerging infectious diseases
The antimalarial drug chloroquine has been suggested as a treatment for Ebola virus infection. Chloroquine inhibited virus replication in vitro, but only at cytotoxic concentrations. In mouse and hamster models, treatment did not improve survival. Chloroquine is not a promising treatment for Ebola. Efforts should be directed toward other drug classes.
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Troy C. Sutton, Elaine W. Lamirande, Kevin W. Bock et al. · 2017 · Journal of Virology
ABSTRACT Influenza viruses of the H1N1, H2N2, and H3N2 subtypes have caused previous pandemics. H2 influenza viruses represent a pandemic threat due to continued circulation in wild birds and limited immunity in the human population. In…
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Nicole Armbruster, Annalisa Lattanzi, M. Jeavons et al. · 2016 · Molecular Therapy — Methods & Clinical Development
Spinal muscular atrophy (SMA) is an autosomal recessive disease of variable severity caused by mutations in the SMN1 gene. Deficiency of the ubiquitous SMN function results in spinal cord α-motor neuron degeneration and proximal muscle…
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Arafat Tfayli, Majd Al Assaad, Ghina Fakhri et al. · 2020 · Cancer Medicine
Multiple randomized studies have shown that combination of chemotherapy and immune checkpoint inhibitors (ICIs) leads to better response rates and survival as compared to chemotherapy alone in the advanced stage of NSCLC. Data suggesting a benefit to using ICIs in the neoadjuvant therapy of patients with early stage NSCLC are emerging. Eligible subjects were treatment naïve patients with stage IB, II, and resectable IIIA NSCLC. Patients received three cycles of neoadjuvant chemotherapy with four doses of avelumab every 2 weeks. Patients with squamous cell cancer received cisplatin or carboplat
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Christian Theilacker, Andrea Kropec, Felix Hammer et al. · 2012 · The Journal of Infectious Diseases
Type 1 lipoteichoic acid (LTA) is present in many clinically important gram-positive bacteria, including enterococci, streptococci, and staphylococci, and antibodies against LTA have been shown to opsonize nonencapsulated Enterococcus…
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Kristen Starbuck, Linah Al-Alem, David A. Eavarone et al. · 2018 · Oncotarget
// Kristen Starbuck 1, 4 , Linah Al-Alem 1, 4 , David A. Eavarone 2 , Silvia Fatima Hernandez 1, 4 , Chiara Bellio 1, 4 , Jillian M. Prendergast 2 , Jenna Stein 2 , Daniel T. Dransfield 2 , Bianca Zarrella 1 , Whitfield B. Growdon 1, 3, 4 , Jeff Behrens 2 , Rosemary Foster 1, 3, 4, * and Bo R. Rueda 1, 3, 4, * 1 Vincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, MA, USA 2 Siamab Therapeutics, Inc., Newton, MA, USA 3 Division of Gynecologic Oncology, Vincent Department of Obstetrics and Gynecology, Massachusetts General Hosp
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Huyen Tran, Tim Brighton, Andrew Grigg et al. · 2014 · British Journal of Haematology
The efficacy of a fixed-dose rituximab schedule was prospectively explored in primary/acute refractory, relapsed or chronic (platelet count >10 × 10(9) /l and ≤50 × 10(9) /l) idiopathic thrombocytopenic purpura (ITP). Patients received two…
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Pol Specenier, Jan B. Vermorken · 2012 · ISRN Oncology
The epidermal growth factor receptor (EGFR) is overexpressed in the vast majority of cases of squamous cell carcinoma of the head and neck (SCCHN). A high EGFR expression is associated with an unfavorable prognosis. Cetuximab is a chimeric human/murine IgG1 antibody which binds with high affinity to the EGFR. It is the only targeted agent which got approval for the treatment of SCCHN from the regulatory agencies of Europe and the United States, both in locoregionally advanced disease, in association with radiation, and in recurrent/metastatic disease. The outcome of trials involving other EGFR
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Kui Yang, Elizabeth Wills, Joel D. Baines · 2011 · Journal of Virology
Herpesvirus genomic DNA is cleaved from concatemers that accumulate in infected cell nuclei. Genomic DNA is inserted into preassembled capsids through a unique portal vertex. Extensive analyses of viral mutants have indicated that intact…
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Per Pfeiffer, Maryam B. Lustberg, Jacques Näsström et al. · 2022 · JNCI Cancer Spectrum
BACKGROUND: Calmangafodipir (CaM, PledOx) demonstrated efficacy in preventing patient-reported chemotherapy-induced peripheral neuropathy (CIPN) in a randomized phase 2 study in patients with metastatic colorectal cancer. The Preventive Treatment of OxaLiplatin Induced peripherAl neuRopathy (POLAR) program aimed to assess efficacy and safety of CaM in the prevention of CIPN in patients treated with oxaliplatin in adjuvant (POLAR-A, ClinicalTrials.gov.NCT04034355) or metastatic (POLAR-M, ClinicalTrials.gov.NCT03654729) settings. METHODS: Two randomized, placebo-controlled phase 3 trials investi
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Robert E. Coleman, Ying Zhou, Danielle Jandial et al. · 2021 · Advances in Therapy
INTRODUCTION: D-CARE, an international, phase 3, randomized, double-blind, placebo-controlled study in women with early-stage breast cancer at high risk of disease recurrence, failed to meet its primary endpoint-improvement in bone…
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John D. Morrey, Venkatraman Siddharthan, Hong Wang et al. · 2012 · PLoS ONE
West Nile virus (WNV) disease can be fatal for high-risk patients. Since WNV or its antigens have been identified in multiple anatomical locations of the central nervous system of persons or rodent models, one cannot know where to investigate the actual mechanism of mortality without careful studies in animal models. In this study, depressed respiratory functions measured by plethysmography correlated strongly with mortality. This respiratory distress, as well as reduced oxygen saturation, occurred beginning as early as 4 days before mortality. Affected medullary respiratory control cells may
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Penelope‐Georgia Papayanni, D. Chasiotis, Kiriakos Koukoulias et al. · 2021 · Clinical Infectious Diseases
BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic poses an urgent need for the development of effective therapies for coronavirus disease 2019 (COVID-19). METHODS: We first tested SARS-CoV-2-specific…
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Harm A.W.M. Tiddens, Eleni‐Rosalina Andrinopoulou, Joe McIntosh et al. · 2020 · PLoS ONE
A phase 3 randomized double blind controlled, trial in 238 people with cystic fibrosis (CF) and at least one nonsense mutation (nmCF) investigated the effect of ataluren on FEV1. The study was of 48 weeks duration and failed to meet its primary endpoint. Unexpectedly, while FEV1 declined, chest computed tomography (CT) scores using the Brody-II score as secondary outcome measures did not show progression in the placebo group. Based on this observation it was concluded that the role of CT scans in CF randomized clinical trials was limited. However, more sensitive scoring systems were developed
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Kalpana Rajanala, Farokh Dotiwala, Arun K. Upadhyay · 2023 · Frontiers in Ophthalmology
Geographic atrophy (GA) is an advanced stage of age-related macular degeneration (AMD) that leads to gradual and permanent vision loss. GA is characterized by the loss of photoreceptor cells and retinal pigment epithelium (RPE), leading to distinct atrophic patches in the macula, which tends to increase with time. Patients with geographic atrophy often experience a gradual and painless loss of central vision, resulting in difficulty reading, recognizing faces, or performing activities that require detailed vision. The primary risk factor for the development of geographic atrophy is advanced ag
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Maria Fortunata Lofiego, Francesca Piazzini, Francesca Pia Caruso et al. · 2024 · Journal of Translational Medicine
BACKGROUND: Glioblastoma multiforme (GBM) is a highly aggressive primary brain tumor, that is refractory to standard treatment and to immunotherapy with immune-checkpoint inhibitors (ICI). Noteworthy, melanoma brain metastases (MM-BM), that share the same niche as GBM, frequently respond to current ICI therapies. Epigenetic modifications regulate GBM cellular proliferation, invasion, and prognosis and may negatively regulate the cross-talk between malignant cells and immune cells in the tumor milieu, likely contributing to limit the efficacy of ICI therapy of GBM. Thus, manipulating the tumor
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Gerrit Frommeyer, Peter Milberg, C. Clauss et al. · 2014 · EP Europace
AIM: The most recent European Society of Cardiology (ESC) update on atrial fibrillation has introduced vernakalant (VER) for pharmacological cardioversion of atrial fibrillation. The aim of the present study was to investigate the safety…
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Carmine Zoccali, Francesca Mallamaci, Luca De Nicola et al. · 2023 · Clinical Kidney Journal
Resistant hypertension (RH) is linked to an increased risk of cardiovascular and renal complications. Treatment options include non-pharmacological interventions, such as lifestyle modifications, and the use of specific antihypertensive…
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James L. Wade, Corey J. Langer, Mary W. Redman et al. · 2017 · Journal of Clinical Oncology
9054 Background: Lung-MAP (S1400) is a National Clinical Trials Network “umbrella” trial for previously-treated SqNSCLC. Sub-study S1400B included patients (pts) with tumors harboring PI3K mutations.Taselisib (GDC-0032), a potent, small…
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Miguel Oliveira Santos, Mamede de Carvalho · 2024 · Expert Review of Neurotherapeutics
INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a rapidly progressive motor neuron disorder with a fatal outcome 3-5 years after disease onset due to respiratory complications. Superoxide dismutase 1 (SOD1) mutations are found in…
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Fiona Carty, Hazel Dunbar, Ian J. Hawthorne et al. · 2021 · Stem Cells Translational Medicine
Cell-based therapy for the treatment of inflammatory disorders has focused on the application of mesenchymal stromal cells (MSCs) and multipotent adult progenitor cells (MAPCs). Despite the recent positive findings in industry-sponsored…
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Weidong Zhao, Gan Zhao, Shuren Zhang et al. · 2018 · Oncotarget
// Weidong Zhao 1 , Gan Zhao 1 , Shuren Zhang 1 , Xianzheng Wang 1 , Xueping Yu 2 and Bin Wang 1 1 Key Laboratory of Medical Molecular Virology of The Ministry of Health and Ministry of Education, School of Basic Medical Sciences, Fudan University, Shanghai, China 2 Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China Correspondence to: Bin Wang, email: bwang3@fudan.edu.cn Keywords: GM-CSF; IFN-α; therapeutic vaccine; HBV; Ly6C hi monocyte Received: April 14, 2017 Accepted: October 30, 2017 Epub
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Anne Kopp, Alexandra Hübner, Florian Zirkel et al. · 2019 · Viruses
. Orthobunyaviruses and pacuviruses are mainly transmitted by blood-feeding insects and infect a variety of vertebrates whereas herbeviruses and shangaviruses have a host range restricted to insects. Here, we tested mosquitoes from a tropical rainforest in Mexico for infections with peribunyaviruses. We identified and characterized two previously unknown viruses, designated Baakal virus (BKAV) and Lakamha virus (LAKV). Sequencing and de novo assembly of the entire BKAV and LAKV genomes revealed that BKAV is an orthobunyavirus and LAKV is likely to belong to a new genus. LAKV was almost equidis
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Sahar Motamedi, Nina Ravoet, Jonas Dehairs et al. · 2025 · Nature Communications
Ferroptosis, a regulated form of cell death driven by lipid peroxidation, holds promise for targeting treatment-resistant cancer cells. Using a panel of melanoma cell lines, we uncover variability in the timing of ferroptosis onset upon…
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