Safety, tolerability, pharmacokinetics, and antitumour activity of oleclumab in Japanese patients with advanced solid malignancies: a phase I, open-label study.

Background: Cluster of differentiation (CD) 73-targeted immunotherapy and CD73 inhibition may reduce adenosine production, which can augment the host and/or immunotherapy response to tumours. We aimed to assess the safety and tolerability, pharmacokinetics, and antitumour activity of oleclumab, an anti-CD73 monoclonal antibody, in adult Japanese patients with advanced solid malignancies resistant to standard therapy.

Methods: In this phase I, single-centre, open-label study, patients received oleclumab 1500 mg (Cohort 1) or 3000 mg (Cohort 2) intravenously every 2 weeks.

Safety, tolerability, pharmacokinetics and preliminary antitumour activity of an antisense oligonucleotide targeting STAT3 (danvatirsen) as monotherapy and in combination with durvalumab in Japanese patients with advanced solid malignancies: a phase 1 study.

Objectives: We assessed the safety, tolerability, pharmacokinetics, preliminary antitumour activity and pharmacodynamics of danvatirsen, an antisense oligonucleotide targeting signal transducer and activator of transcription 3 (STAT3), monotherapy and danvatirsen plus durvalumab, an antiprogrammed cell death ligand 1 monoclonal antibody, in patients with advanced solid malignancies.

Design: Phase 1, open-label study with two cohorts.

Setting: Two centres in Japan.

Savolitinib ± Osimertinib in Japanese Patients with Advanced Solid Malignancies or EGFRm NSCLC: Ph1b TATTON Part C.

Background: Preliminary data suggest that combining savolitinib, a potent and highly selective MET-tyrosine kinase inhibitor (TKI), with osimertinib, a third-generation, irreversible, oral epidermal growth factor receptor-TKI (EGFR-TKI), may overcome MET-based resistance to EGFR-TKIs.

Objective: To investigate the safety and tolerability of savolitinib in Japanese patients with advanced solid malignancies.

Patients And Methods: In Part C of the phase Ib, multi-arm, open-label, multicenter TATTON study, two cohorts of Japanese adult patients were evaluated across six study centers in Japan.

A molded hyaluronic acid gel as a micro-template for blood capillaries.

Fabrication of blood capillaries in tissue-engineered tissue is necessary for creating thick three-dimensional (3D) tissue with a high cellular density. For inducing blood capillaries in the tissue in vitro, a molded hyaluronic acid (HA) capillary-shaped gel was made as a template for blood capillaries by photolithography and power free pumping techniques. The fabricated HA capillary-shaped gel was sandwiched between two cell sheets consisting of neonatal normal human dermal fibroblasts (NHDFs), human umbilical vein endothelial cells (HUVECs), or co-cultured NHDFs and HUVECs, and eventually covered with the cells.

Displacement of tight junction proteins from detergent-resistant membrane domains by treatment with sodium caprate.

We have investigated the effect of sodium salt of capric acid (C10) on major tight junction proteins such as claudin and occludin, and also examined the involvement of lipid rafts with C10-induced alterations on these proteins. We firstly examined the C10 effect on the barrier function of tight junctions by measuring transepithelial electrical resistance (TER) and the flux of FITC dextran 4400 (FD-4). As a result, the increase in the FD-4 flux and decrease in the TER value were observed by incubation with C10 (10 mM) for 30 min, suggesting loss of the barrier function.

Specific effect of polyunsaturated fatty acids on the cholesterol-poor membrane domain in a model membrane.

To understand more fully the effect of polyunsaturated fatty acids (PUFAs) on lipid bilayers, we investigated the effects of treatment with fatty acids on the properties of a model membrane. Three kinds of liposomes comprising dipalmitoylphosphatidylcholine (DPPC), dioleylphosphatidylcholine (DOPC), and cholesterol (Ch) were used as the model membrane, and the fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH) and detergent insolubility were determined. Characterization of the liposomes clarified that DPPC, DPPC/Ch, and DPPC/DOPC/Ch existed as solid-ordered phase (L beta), liquid-ordered phase (l o), and a mixture of l o and liquid-disordered phase (L alpha) membranes at room temperature.