Circulating tumour DNA biomarkers in savolitinib-treated patients with non-small cell lung cancer harbouring exon 14 skipping alterations: a analysis of a pivotal phase 2 study.

Background: Savolitinib, a selective MET inhibitor, showed efficacy in patients with non-small cell lung cancer (NSCLC), including pulmonary sarcomatoid carcinoma (PSC), harbouring exon 14 skipping alteration (ex14).

Objective: To analyse , the association between circulating tumour DNA (ctDNA) biomarkers and clinical outcomes, including resistance, with savolitinib.

Design: A multicentre, single-arm, open-label phase 2 study.

Long-Term Efficacy, Safety, and Subgroup Analysis of Savolitinib in Chinese Patients With NSCLCs Harboring Exon 14 Skipping Alterations.

Introduction: Savolitinib has been found to have encouraging antitumor activity and a favorable safety profile in Chinese patients with pulmonary sarcomatoid carcinoma and other NSCLCs with exon 14 skipping alterations ( ex14 positive) at the primary analysis of a phase 2 study. Here, we present the long-term efficacy and safety data of savolitinib, including subgroup analyses.

Methods: This multicenter, single-arm, open-label, phase 2 study in the People's Republic of China enrolled MET inhibitor-naive adults with locally advanced or metastatic ex14-positive NSCLC (NCT02897479).

Safety and Efficacy of Epitinib for EGFR-Mutant Non-Small Cell Lung Cancer With Brain Metastases: Open-Label Multicentre Dose-Expansion Phase Ib Study.

Background: Non-small-cell lung cancer (NSCLC) had poor prognosis in patients with brain metastasis. The trial evaluated the safety and efficacy of epitinib (HMPL-813), an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), for EGFR-mutant NSCLC with brain metastasis.

Patients And Methods: This open-label, dose-expansion phase Ib study (ClinicalTrials.

The circulating ANGPTL8 levels show differences among novel subgroups of adult patients with diabetes and are associated with mortality in the subsequent 5 years.

ANGPTL8, an important regulator of glucose and lipid metabolism, is associated with diabetes, but the role of ANGPTL8 in the outcomes of novel subgroups of diabetes remains unclear. To assess the circulating ANGPTL8 levels in novel subgroups of diabetes and their association with health outcomes, we performed a data-driven cluster analysis (k-means) of patients with newly diagnosed diabetes (741 patients enrolled from 2011 through 2016) from the Risk Evaluation of Cancers in Chinese Diabetic Individuals: a longitudinal (REACTION) study. The primary outcomes were mortality from all causes and cardiovascular diseases (CVD), and the secondary outcome was any cardiovascular event.

Insulin upregulates betatrophin expression via PI3K/Akt pathway.

Betatrophin is regarded as a liver-produced hormone induced by insulin resistance (IR). However, it remains largely unknown how IR regulates betatrophin expression. To study whether IR could regulate betatrophin expression and the corresponding molecular mechanisms, betatrophin levels were examined in 6 in vitro IR models which were established using human hepatocytes L02 with different agents, including tumor necrosis factor-α, interleukin-1β, dexamethasone, palmitate, high glucose and insulin and betatrophin levels were elevated only in the insulin group.

Incretin-based agents in type 2 diabetic patients at cardiovascular risk: compare the effect of GLP-1 agonists and DPP-4 inhibitors on cardiovascular and pancreatic outcomes.

Background: Incretin-based agents, including dipeptidyl peptidase-4 inhibitors (DPP-4Is) and glucagon-like peptide-1 agonists (GLP-1As), work via GLP-1 receptor for hyperglycemic control directly or indirectly, but have different effect on cardiovascular (CV) outcomes. The present study is to evaluate and compare effects of incretin-based agents on CV and pancreatic outcomes in patients with type 2 diabetes mellitus (T2DM) and high CV risk.

Methods: Six prospective randomized controlled trials (EXMAINE, SAVOR-TIMI53, TECOS, ELIXA, LEADER and SUSTAIN-6), which included three trials for DPP-4Is and three trials for GLP-1As, with 55,248 participants were selected to assess the effect of different categories of incretin-based agents on death, CV outcomes (CV mortality, major adverse CV events, nonfatal myocardial infarction, nonfatal stroke, heart failure hospitalization), pancreatic events (acute pancreatitis and pancreatic cancer) as well as on hypoglycemia.

TIGIT negatively regulates inflammation by altering macrophage phenotype.

Macrophages function as an essential component of innate immune system, contributing to both the initiation and appropriate resolution of inflammation. The exposure of macrophages to the microbial products, such as lipopolysaccharide (LPS), can strongly shift the balance between tissue homeostasis and inflammation in favor of causing systemic damage, in which macrophage M1 polarization play important roles. Strategies aiming at restoring the balance of macrophage polarization remain to be further explored.

Circulating betatrophin levels are increased in patients with type 2 diabetes and associated with insulin resistance.

Context: Betatrophin has recently attracted increasing interests as a potential β-cell regenerative therapy in diabetes. However, differences in betatrophin profiles in patients with type 2 diabetes mellitus (T2DM) remain unclear.

Objective: The objective of the study was to examine circulating betatrophin levels in subjects with different glucose tolerance status and its correlation with insulin resistance.