A Phase III Randomized Trial of Integrated Genomics and Avatar Models for Personalized Treatment of Pancreatic Cancer: the AVATAR Trial.

Purpose: Pancreatic adenocarcinoma (PDAC) has limited treatment options. We compared the efficacy of comprehensive precision medicine against the conventional treatment in PDAC.

Methods: Phase III trial of advanced PDAC where patients were randomized (1:2) to a conventional treatment treated at physician's discretion (arm A), or to precision medicine (arm B).

In vivo phosphoproteomics reveals kinase activity profiles that predict treatment outcome in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) lacks prognostic and predictive markers. Here, we use high-throughput phosphoproteomics to build a functional TNBC taxonomy. A cluster of 159 phosphosites is upregulated in relapsed cases of a training set (n = 34 patients), with 11 hyperactive kinases accounting for this phosphoprofile.

Ghrelin's Effects on Proinflammatory Cytokine Mediated Apoptosis and Their Impact on β-Cell Functionality.

Ghrelin is a peptidic hormone, which stimulates cell proliferation and inhibits apoptosis in several tissues, including pancreas. In preclinical stage of type 1 diabetes, proinflammatory cytokines generate a destructive environment for β-cells known as insulitis, which results in loss of β-cell mass and impaired insulin secretion, leading to diabetes. Our aim was to demonstrate that ghrelin could preserve β-cell viability, turnover rate, and insulin secretion acting as a counter balance of cytokines.

Cyclin C stimulates β-cell proliferation in rat and human pancreatic β-cells.

Activation of pancreatic β-cell proliferation has been proposed as an approach to replace reduced functional β-cell mass in diabetes. Quiescent fibroblasts exit from G0 (quiescence) to G1 through pRb phosphorylation mediated by cyclin C/cdk3 complexes. Overexpression of cyclin D1, D2, D3, or cyclin E induces pancreatic β-cell proliferation.

Epoxypukalide induces proliferation and protects against cytokine-mediated apoptosis in primary cultures of pancreatic β-cells.

There is an urgency to find new treatments for the devastating epidemic of diabetes. Pancreatic β-cells viability and function are impaired in the two most common forms of diabetes, type 1 and type 2. Regeneration of pancreatic β-cells has been proposed as a potential therapy for diabetes.

Increased Aβ production prompts the onset of glucose intolerance and insulin resistance.

Type 2 diabetes (T2D) mellitus and Alzheimer's disease (AD) are two prevalent diseases with comparable pathophysiological features and genetic predisposition. Patients with AD are more susceptible to develop T2D. However, the molecular mechanism linking AD and T2D remains elusive.