Validation of the graded prognostic assessment and recursive partitioning analysis as prognostic tools using a modern cohort of patients with brain metastases.

Background: Prognostic indices for patients with brain metastases (BM) are needed to individualize treatment and stratify clinical trials. Two frequently used tools to estimate survival in patients with BM are the recursive partitioning analysis (RPA) and the diagnosis-specific graded prognostic assessment (DS-GPA). Given recent advances in therapies and improved survival for patients with BM, this study aims to validate and analyze these 2 models in a modern cohort.

Alpha- to Beta-Cell Transdifferentiation in Neonatal Compared with Adult Mouse Pancreas in Response to a Modest Reduction in Beta-Cells Using Streptozotocin.

Following the near-total depletion of pancreatic beta-cells with streptozotocin (STZ), a partial recovery of beta-cell mass (BCM) can occur, in part due to the alpha- to beta-cell transdifferentiation with an intermediary insulin/glucagon bi-hormonal cell phenotype. However, human type 2 diabetes typically involves only a partial reduction in BCM and it is not known if recovery after therapeutic intervention involves islet cell transdifferentiation, or how this varies with age. Here, we used transgenic mouse models to examine if islet cell transdifferentiation contributes to BCM recovery following only a partial depletion of BCM.

Tumour-selective activity of RAS-GTP inhibition in pancreatic cancer.

Broad-spectrum RAS inhibition has the potential to benefit roughly a quarter of human patients with cancer whose tumours are driven by RAS mutations. RMC-7977 is a highly selective inhibitor of the active GTP-bound forms of KRAS, HRAS and NRAS, with affinity for both mutant and wild-type variants. More than 90% of cases of human pancreatic ductal adenocarcinoma (PDAC) are driven by activating mutations in KRAS.