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Neoadjuvant anti-PD1 immunotherapy for surgically accessible recurrent glioblastoma: clinical and molecular outcomes of a stage 2 single-arm expansion cohort.
Nat Commun
December 2024
Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Glioblastoma is immunologically "cold" and resistant to single-agent immune-checkpoint inhibitors (ICI). Our previous study of neoadjuvant pembrolizumab in surgically-accessible recurrent glioblastoma identified a molecular signature of response to ICI and suggested that neoadjuvant pembrolizumab may improve survival. To increase the power of this observation, we enrolled an additional 25 patients with a primary endpoint of evaluating the cell cycle gene signature associated with neoadjuvant pembrolizumab and performed bulk-RNA seq on resected tumor tissue (NCT02852655).
View Article and Find Full Text PDFComprehensive molecular characterization to predict immunotherapy response in advanced biliary tract cancer: a phase II trial of pembrolizumab.
Oncol Res
December 2024
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Background: Immune checkpoint inhibitors (ICIs) are effective in a subset of patients with metastatic solid tumors. However, the patients who would benefit most from ICIs in biliary tract cancer (BTC) are still controversial.
Materials And Methods: We molecularly characterized tissues and blood from 32 patients with metastatic BTC treated with the ICI pembrolizumab as second-line therapy.
Reduced gut microbiota diversity in ulcerative colitis patients with latent tuberculosis infection during vedolizumab therapy: insights on prophylactic anti-tuberculosis effects.
BMC Microbiol
December 2024
Department of Gastroenterology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, No.365 Renming East Road, Jinhua, Zhejiang, P. R. China.
Background: The gut microbiota plays a pivotal role in ulcerative colitis (UC) development. This study explores the impact of latent tuberculosis infection (LTBI) on the gut microbiota in UC and assesses changes during vedolizumab treatment, investigating prophylactic anti-tuberculosis therapy.
Results: This cohort study included adult patients with UC receiving vedolizumab treatment at Jinhua Hospital, Zhejiang University from April 2021 to December 2022.
Mevalonate kinase inhibits anti-tumor immunity by impairing the tumor cell-intrinsic interferon response in microsatellite instability colorectal cancer.
Oncogene
December 2024
Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China.
Article Synopsis
- Insufficient interferon response in tumor cells limits the effectiveness of immune checkpoint blockade (ICB) therapy, particularly in anti-PD-1 treatment for microsatellite instability (MSI) colorectal cancer (CRC).
- Through screening, the study identified mevalonate kinase (MVK) as a key negative regulator of this interferon response in MSI CRC cells, where its genetic removal led to better immune cell infiltration and tumor growth suppression in mice.
- The research highlighted that lowered MVK expression in human tumor samples associates with improved responses to anti-PD-1 therapy, indicating that targeting MVK could enhance ICB therapy by boosting interferon signaling in MSI CRC patients.
In vivo hyperphosphorylation of tau is associated with synaptic loss and behavioral abnormalities in the absence of tau seeds.
Nat Neurosci
December 2024
Laboratory for Proteolytic Neuroscience, RIKEN Center for Brain Science, Wako, Japan.
Tau pathology is a hallmark of several neurodegenerative diseases, including frontotemporal dementia and Alzheimer's disease. However, the sequence of events and the form of tau that confers toxicity are still unclear, due in large part to the lack of physiological models of tauopathy initiation and progression in which to test hypotheses. We have developed a series of targeted mice expressing frontotemporal-dementia-causing mutations in the humanized MAPT gene to investigate the earliest stages of tauopathy.
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