A Mouse Model to Assess STAT3 and STAT5A/B Combined Inhibition in Health and Disease Conditions.

Genetically-engineered mouse models (GEMMs) lacking diseased-associated gene(s) globally or in a tissue-specific manner represent an attractive tool with which to assess the efficacy and toxicity of targeted pharmacological inhibitors. and transcription factors have been implicated in several pathophysiological conditions, and pharmacological inhibition of both transcription factors has been proposed to treat certain diseases, such as malignancies. To model combined inhibition of and we have developed a GEMM harboring a flox - allele ( mice) and generated mice lacking and in hepatocytes ().

Anticoagulation strategy in a patient on the HeartMate III® left ventricular assist device with acquired von Willebrand syndrome and recurring gastrointestinal bleeding episodes: sometimes less is more.

Acquired von Willebrand syndrome is a frequently encountered complication of continuous flow ventricular assist devices, which may lead to clinically relevant bleeding in up to 30% of patients after continuous flow ventricular assist device implantation. As standard anticoagulation strategies may be detrimental, individualized treatment is called for, as described in our patient on the HeartMate III® left ventricular assist device.

CDK6 coordinates mutant MPN via NF-κB and apoptotic networks.

Over 80% of patients with myeloproliferative neoplasms (MPNs) harbor the acquired somatic mutation. JAK inhibition is not curative and fails to induce a persistent response in most patients, illustrating the need for the development of novel therapeutic approaches. We describe a critical role for CDK6 in MPN evolution.

Afatinib restrains K-RAS-driven lung tumorigenesis.

On the basis of clinical trials using first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), it became a doctrine that V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog () mutations drive resistance to EGFR inhibition in non-small cell lung cancer (NSCLC). Conversely, we provide evidence that EGFR signaling is engaged in K-RAS-driven lung tumorigenesis in humans and in mice. Specifically, genetic mouse models revealed that deletion of quenches mutant K-RAS activity and transiently reduces tumor growth.

AKT3 drives adenoid cystic carcinoma development in salivary glands.

Salivary gland cancer is an aggressive and painful cancer, but a rare tumor type accounting for only ~0.5% of cancer cases. Tumors of the salivary gland exhibit heterogeneous histologic and genetic features and they are subdivided into different subtypes, with adenoid cystic carcinomas (ACC) being one of the most abundant.