Long-term persistence of glycemic dysregulation in patients with a history of pheochromocytoma/paraganglioma.

Context: Pheochromocytomas and paragangliomas (PPGLs) are rare endocrine tumors that frequently produce catecholamines. Catecholamine-induced cardiometabolic complications substantially contribute to increased morbidity and mortality in PPGL patients prior to surgical resection.

Objective: To determine whether markers of elevated cardiometabolic risk persist in patients following PPGL resection.

Detection rate of colorectal cancer by routine colonoscopy is comparable in patients aged 45-49 and 50-54 years.

Objectives: Colorectal carcinoma remains one of the most common malignancies worldwide. Colonoscopy screening is most effective for early detection and tumour prevention and is currently recommended in Europe for adults aged over 50 years. However, given that an increasing proportion of patients are diagnosed before the age of 50, we set out to determine the detection rate of colorectal carcinoma in patients younger than 50 years and to determine the best threshold for starting colonoscopy screening.

Ex vivo modeling of acquired drug resistance in BRAF - mutated pancreatic cancer organoids uncovers individual therapeutic vulnerabilities.

Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis due to late detection and limited treatment options. Some PDAC patients harbor alterations that qualify for targeted treatment strategies but develop acquired resistance, leading to treatment failure. We here report the ex vivo modeling of acquired drug resistance by creating a PDAC patient-derived tumor organoid (PDTO) model harboring a rare BRAF R506_K507ins VLR mutation resulting in a resistance to trametinib, a MEK inhibitor.

In-depth mechanistic analysis including high-throughput RNA sequencing in the prediction of functional and structural cardiotoxicants using hiPSC cardiomyocytes.

Background: Cardiotoxicity remains one of the most reported adverse drug reactions that lead to drug attrition during pre-clinical and clinical drug development. Drug-induced cardiotoxicity may develop as a functional change in cardiac electrophysiology (acute alteration of the mechanical function of the myocardium) and/or as a structural change, resulting in loss of viability and morphological damage to cardiac tissue.

Research Design And Methods: Non-clinical models with better predictive value need to be established to improve cardiac safety pharmacology.

Impact of the PI3K-alpha inhibitor alpelisib on everolimus resistance and somatostatin receptor expression in an orthotopic pancreatic NEC xenograft mouse model.

The mechanistic target of rapamycin complex 1 (mTORC1) inhibitor everolimus is one of the few approved therapies for locally advanced and metastatic neuroendocrine tumours (NETs). However, after initial disease stabilisation, most patients develop resistance within 1 year. Our aim was to overcome resistance to everolimus by additional treatment with the PI3K-alpha inhibitor alpelisib in an everolimus-resistant orthotopic pancreatic neuroendocrine carcinoma xenograft mouse model.