Pembrolizumab Plus Carboplatin and Paclitaxel as First-Line Therapy for Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (KEYNOTE-B10): A Single-Arm Phase IV Trial.

Purpose: Standard-of-care first-line treatment for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) is pembrolizumab plus platinum and fluorouracil (FU). However, FU is associated with potential challenges (continuous 4-day infusion, high administration costs, and cardiovascular and gastrointestinal toxicities), creating a clinical need for alternative chemotherapy combinations. We evaluated the efficacy and safety of first-line pembrolizumab plus carboplatin and paclitaxel for R/M HNSCC in the open-label, single-arm, phase IV KEYNOTE-B10 study (ClinicalTrials.

Clinical outcomes and prognostic factors in cisplatin versus cetuximab chemoradiation for locally advanced p16 positive oropharyngeal carcinoma.

Objectives: Randomized trials evaluating cisplatin versus cetuximab chemoradiation (CRT) for p16+ oropharyngeal cancer (OPC) have yet to report preliminary data. Meanwhile, as a preemptive step toward morbidity reduction, the off-trial use of cetuximab in p16+ patients is increasing, even in those who could potentially tolerate cisplatin. The purpose of this study was to compare the efficacy of cisplatin versus cetuximab CRT in the treatment of p16+ OPC and to identify prognostic factors and predictors of tumor response.

Phase II evaluation of docetaxel-modulated capecitabine in previously treated patients with non-small cell lung cancer.

Purpose: Based on the preclinical observation of upregulation of thymidine phosphorylase, the last enzymatic step in the conversion of capecitabine to 5-fluorouracil, by docetaxel along with good clinical tolerability of the combination of docetaxel and capecitabine using an optimized schedule in a previous phase I trial, we conducted this phase II study of this combination in patients with refractory or relapsed non-small cell lung cancer (NSCLC).

Patients And Methods: Patients with NSCLC previously treated with at least one platinum- or paclitaxel-based regimen received docetaxel 36 mg/m(2) on days 1, 8, and 15 and capecitabine 625 mg/m(2) twice daily on days 5 to 18, every 4 weeks. The primary objective of the study was evaluation of progression-free survival (PFS) 26 weeks from initiation of treatment.

Bidirectional regulation of neurite elaboration by alternatively spliced metabotropic glutamate receptor 5 (mGluR5) isoforms.

Alternative splicing in the mGluR5 gene generates two different receptor isoforms, of which expression is developmentally regulated. However, little is known about the functional significance of mGluR5 splice variants. We have examined the functional coupling, subcellular targeting, and effect on neuronal differentiation of epitope-tagged mGluR5 isoforms by expression in neuroblastoma NG108-15 cells.

Competitive interaction of seven in absentia homolog-1A and Ca2+/calmodulin with the cytoplasmic tail of group 1 metabotropic glutamate receptors.

Background: Group 1 metabotropic glutamate receptors (mGluR1 and mGluR5) are coupled to inositol trisphosphate/Ca2+ signaling via G proteins and play an important role in excitatory synaptic transmission. To explore the regulation of group 1 mGluR function, we applied the yeast two-hybrid system using the intracellular carboxy-terminal domain of group 1 mGluRs (group 1 ct-mGluRs) and attempted to identify novel protein-protein interactions of group 1 mGluRs.

Results: The two-hybrid screening revealed a specific interaction between group 1 ct-mGluRs and Siah-1A, the mammalian homolog of Drosophila seven in absentia which is involved in photoreceptor cell differentiation via the ubiquitin/proteasome-dependent mechanism.