Targeting GOF p53 and c-MYC through LZK Inhibition or Degradation Suppresses Head and Neck Tumor Growth.

The worldwide frequency of head and neck squamous cell carcinoma (HNSCC) is approximately 800,000 new cases, with 430,000 deaths annually. We determined that LZK (encoded by ) is a therapeutic target in HNSCC and showed that inhibition with small molecule inhibitors decreases the viability of HNSCC cells with amplified . A drug-resistant mutant of LZK blocks decreases in cell viability due to LZK inhibition, indicating on-target activity by two separate small molecules.

Selective Degradation of MLK3 by a Novel CEP1347-VHL-02 PROTAC Compound Limits the Oncogenic Potential of TNBC.

Triple-negative breast cancer (TNBC) is associated with poor prognosis because of the lack of effective therapies. Mixed-lineage protein kinase 3 (MLK3) is a protein that is often upregulated in TNBC and involved in driving the tumorigenic potential of cancer cells. Here, we present a selective MLK3 degrader, CEP1347-VHL-02, based on the pan-MLK inhibitor CEP1347 and a ligand for E3 ligase von Hippel-Lindau (VHL) by employing proteolysis-targeting chimera (PROTAC) technology.

Exposure to chemical pollutants and biological aerosol in indoor facilities for recreational and sport horses.

Background: Due to the increasing prevalence of equine non-infectious respiratory disease, the air contamination in equine housing (Stables A-C) and training facilities (indoor riding arenas A - C) was investigated. The aim of the study was to monitor gaseous pollutants, bioaerosols, and dust concentrations at three different sites (stables and riding halls), where different floor materials were used in the riding halls.

Materials And Methods: Air quality was monitored in housing for horses and in riding halls in terms of dust concentration, the presence of gaseous chemical pollutants, and concentrations of biological aerosol.

Pilot Study: FSHR Expression in Neuroendocrine Tumors of the Appendix.

Appendix neuroendocrine neoplasm (ANEN) treatment is based on tumor size and proliferation markers. Recently, the role of the follicle-stimulating hormone receptor (FSHR) from the clinical perspective has also been increasingly discussed. The FSHR is expressed in the endothelial cells of both intratumoral and peritumoral blood vessels, where it contributes to neoangiogenesis and blood vessel remodeling.

SARS-COVID-19 TRIGGERED WERNICKE'S ENCEPHALOPATHY (CLINICAL CASE).

Patient P., born in 1956, was found by relatives in a state of confused consciousness, an act of involuntary urination and defecation, numbness and weakening of the strength of both lower limbs were recorded. He was taken by ambulance to the reception room of the Regional Clinical Center of Neurosurgery and Neurology.