Targeting BCL2 with Venetoclax Enhances the Efficacy of the KRASG12D Inhibitor MRTX1133 in Pancreatic Cancer.

MRTX1133 is currently being evaluated in patients with pancreatic ductal adenocarcinoma (PDAC) tumors harboring a KRASG12D mutation. Combination strategies have the potential to enhance the efficacy of MRTX1133 to further promote cell death and tumor regression. In this study, we demonstrated that MRTX1133 increased the levels of the proapoptotic protein BIM in PDAC cells and conferred sensitivity to the FDA-approved BCL2 inhibitor venetoclax.

Loss of STK11 Suppresses Lipid Metabolism and Attenuates KRAS-Induced Immunogenicity in Patients with Non-Small Cell Lung Cancer.

Unlabelled: As many as 30% of the patients with non-small cell lung cancer harbor oncogenic KRAS mutations, which leads to extensive remodeling of the tumor immune microenvironment. Although co-mutations in several genes have prognostic relevance in KRAS-mutated patients, their effect on tumor immunogenicity are poorly understood. In the present study, a total of 189 patients with non-small cell lung cancer underwent a standardized analysis including IHC, whole-exome DNA sequencing, and whole-transcriptome RNA sequencing.

Diabetic ketoacidosis masked by both Euglycemia and a primary metabolic alkalosis.

Diabetic ketoacidosis (DKA) is an acute, life-threatening metabolic complication of diabetes classically associated with hyperglycemia, metabolic acidosis, and ketosis. Though relatively uncommon, patients can also develop DKA with relative euglycemia, further complicating diagnosis. Here, we describe the case of a patient who presented with intractable vomiting secondary to diabetic gastroparesis.

Hereditary Spherocytosis with Mitochondrial Retention, Increased Oxidative Stress, and Alterations to Bioactive Membrane Lipids.

The clinical course for Hereditary Spherocytosis (HS) patients is highly varied, even within families with identical driving mutations. Here, we describe four siblings with HS attributed to an unreported SPTB mutation. All patients displayed an increased fraction of mitochondria-positive erythrocytes.

Chromium (VI) promotes lung cancer initiation by activating EGF/ALDH1A1 signalling.

Lung cancer is the leading cause of cancer-related death worldwide and is strongly associated with tobacco smoke exposure. Though smoking remains the most important and best studied risk factor, recent data suggests that several other carcinogens have a driving role in lung cancer development, particularly in select populations at risk of high or prolonged exposure. Hexavalent chromium [Cr(VI)] is a known carcinogen that is widely used in the manufacturing industry.