The proneural subtype was identified by frequent positive IDH1 expression and high Olig2 and Ki67 expression. Immune-phenotyping showed that mesenchymal and IGS 23 tumors exhibited a higher positive effector cell score, a higher negative suppressor cell score, and lower levels of immune checkpoint molecules. The cell-type deconvolution analysis revealed that these tumors are highly enriched in M2 macrophages, resting memory CD4
T cells, and activated dendritic cells, indicating that they may be ideal candidates for immunotherapy, especially with anti-M2 and/or dendritic cell vaccination.
There is a subset of tumors, frequently classified as mesenchymal or IGS cluster 23, that may be identified with IHC and could well be optimal candidates for immunotherapy.
There is a subset of tumors, frequently classified as mesenchymal or IGS cluster 23, that may be identified with IHC and could well be optimal candidates for immunotherapy.
Statins are cholesterol-depleting drugs used to treat patients with hypercholesterolemia. Preclinically, statins disrupt trafficking of receptors present at the cell membrane. Membrane receptors, defined as tumor biomarkers and therapeutic targets, are often internalized by an endocytic pathway. Indeed, receptor endocytosis and recycling are dynamic mechanisms that often affect receptor density at the cell surface. In therapies using monoclonal antibodies (mAb), a downregulation in receptor density at the cell surface decreases antibody binding to the extracellular domain of the membrane receptor. learn more Here, we determined the potential of lovastatin, simvastatin, and rosuvastatin in preclinically modulating epidermal growth factor receptor (EGFR) and prostate-specific membrane antigen (PSMA) receptor density at the tumor cell surface.
Small-animal PET was used to study the binding of
Zr-labeled antibodies in ectopic xenografts.
analyses were performed to determine changes in endocytic proteins, EGFR, and associated with poor response in tumors to therapeutic antibodies.The APOLLO investigators showed that next-generation sequencing of cerebrospinal fluid can reveal molecular alterations-how should this affect our management approach?See related article by Xing et al., p. 6168.
To evaluate the effect of triglyceride deposit cardiomyovasculopathy (TGCV) on the cardiovascular outcomes in haemodialysis (HD) patients with suspected coronary artery disease (CAD).
This retrospective single-centre observational study included data from the cardiac catheter database of Narita Memorial Hospital between April 2011 and March 2017. Among 654 consecutive patients on HD, the data for 83 patients with suspected CAD who underwent both [
I]-β-methyl-iodophenyl-pentadecanoic acid scintigraphy and coronary angiography were analysed. Patients were divided into three groups definite TGCV (17 patients), probable TGCV (22 patients) and non-TGCV control group (44 patients). The primary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction and non-fatal stroke assessed for up to 5 years of follow-up.
The prevalence of definite TGCV was approximately 20% and 2.6% among consecutive HD patients with suspected CAD and among all HD patients, respectively. At the end of the median follow-up period of 4.7 years, the primary endpoint was achieved in 52.9% of the definite TGCV patients (HR, 7.45; 95% CI 2.28 to 24.3; p<0.001) and 27.3% of the probable TGCV patients (HR, 3.28; 95% CI 0.93 to 11.6; p=0.066), compared with that in 9.1% of the non-TGCV control patients. Definite TGCV was significantly and independently associated with cardiovascular mortality and outcomes among HD patients in all multivariate models.
TGCV is not uncommon in HD patients and is associated with an increased risk of cardiovascular events including cardiovascular death. Thus, TGCV might be a potential therapeutic target.
TGCV is not uncommon in HD patients and is associated with an increased risk of cardiovascular events including cardiovascular death. Thus, TGCV might be a potential therapeutic target.Accumulating evidence has established a firm role for synaptic plasticity in the pathogenesis of neuropathic pain. Recent advances have highlighted the importance of dendritic spine remodeling in driving synaptic plasticity within the CNS. Identifying the molecular players underlying neuropathic pain induced structural and functional maladaptation is therefore critical to understanding its pathophysiology. This process of dynamic reorganization happens in unique phases that have diverse pathologic underpinnings in the initiation and maintenance of neuropathic pain. Recent evidence suggests that pharmacological targeting of specific proteins during distinct phases of neuropathic pain development produces enhanced antinociception. These findings outline a potential new paradigm for targeted treatment and the development of novel therapies for neuropathic pain. We present a concise review of the role of dendritic spines in neuropathic pain and outline the potential for modulation of spine dynamics by targeting two proteins, srGAP3 and Rac1, critically involved in the regulation of the actin cytoskeleton.
Several Chinese cities have implemented dispatcher-assisted cardiopulmonary resuscitation (DA-CPR), although out-of-hospital cardiac arrest (OHCA) survival rates remain low. We aimed to assess the process compliance, barriers and outcomes of OHCA in one of the earliest implemented (DA-CPR) programmes in China.
We retrospectively reviewed OHCA emergency dispatch records of Suzhou emergency medical service from 2014 to 2015 and included adult OHCA victims (>18 years) with a bystander-witnessed atraumatic OHCA that was subsequently confirmed by on-site emergency physician. The circumstances and DA-CPR process related to the OHCA event were analysed. Dispatch audio records were reviewed to identify potential barriers to implementation during the DA-CPR process.
Of the 151 OHCA victims, none survived. The median time from patient collapse to call for emergency services and that from call to provision of cardiopulmonary resuscitation instructions was 30 (IQR 20-60) min and 115 (IQR 90-153) s, respectively.learn more
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