Phase 1 study of anti-CD47 monoclonal antibody CC-90002 in patients with relapsed/refractory acute myeloid leukemia and high-risk myelodysplastic syndromes.

CC-90002 is an anti-CD47 antibody that inhibits CD47-SIRPα interaction and enables macrophage-mediated killing of tumor cells in hematological cancer cell lines. In this first clinical, phase 1, dose-escalation and -expansion study (CC-90002-AML-001; NCT02641002), we evaluated CC-90002 in patients with relapsed/refractory acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (MDS). CC-90002 was administered in escalating doses of 0.

Removal of calcium hydroxide intracanal medicament by different irrigants and irrigating techniques: a cone beam computed tomography analysis.

The aim of this study was to use cone beam computed tomography (CBCT) to evaluate the removal of calcium hydroxide (Ca[OH]2) from root canals after using different irrigation and activation protocols. Root canals (n = 128) were filled with Ca(OH)2 and scanned using CBCT. The Ca(OH)2 was removed after 1 week using 1 of 12 groups (G1-G12) according to the final irrigating solution: G1, 6% sodium hypochlorite (NaOCl) + 18% etidronic acid (EA) with no activation; G2, NaOCL + EA + passive ultrasonic irrigation (PUI); G3, NaOCl + EA + Finishing File (FF); G4, NaOCl + EA + NaviTip FX irrigation needle (NTFX); G5, 3% NaOCl + 17% ethylenediaminetetraacetic acid (EDTA) with no activation; G6, NaOCl + EDTA + PUI; G7, NaOCl + EDTA + FF; G8, NaOCl + EDTA + NTFX; G9, 3% NaOCl with no activation; G10, NaOCl + PUI; G11, NaOCl + FF; G12, NaOCL + NTFX.

Current Approaches for Absorption, Distribution, Metabolism, and Excretion Characterization of Antibody-Drug Conjugates: An Industry White Paper.

An antibody-drug conjugate (ADC) is a unique therapeutic modality composed of a highly potent drug molecule conjugated to a monoclonal antibody. As the number of ADCs in various stages of nonclinical and clinical development has been increasing, pharmaceutical companies have been exploring diverse approaches to understanding the disposition of ADCs. To identify the key absorption, distribution, metabolism, and excretion (ADME) issues worth examining when developing an ADC and to find optimal scientifically based approaches to evaluate ADC ADME, the International Consortium for Innovation and Quality in Pharmaceutical Development launched an ADC ADME working group in early 2014.

Photoactivation of curcumin and sodium hypochlorite to enhance antibiofilm efficacy in root canal dentin.

Background: To test the effect of ultrasonic or light activated curcumin and sodium hypochlorite against Enterococcus faecalis biofilms in vitro.

Methods: E. faecalis biofilms were grown within root canals (n=175) and divided into 7 groups (n=25).

Antibiofilm activity of three irrigation protocols activated by ultrasonic, diode laser or Er:YAG laser in vitro.

Aim: To investigate the impact of three irrigation protocols, activated by three different methods, on mature biofilms of Enterococcus faecalis in vitro.

Methodology: Root canals in 280 single-rooted teeth were instrumented using a rotary Ni-Ti system. Biofilms of E.

Ligand binding assay critical reagents and their stability: recommendations and best practices from the Global Bioanalysis Consortium Harmonization Team.

The L4 Global Harmonization Team on reagents and their stability focused on the management of critical reagents for pharmacokinetic, immunogenicity, and biomarker ligand binding assays. Regulatory guidance recognizes that reagents are important for ligand binding assays but do not address numerous aspects of critical reagent life cycle management. Reagents can be obtained from external vendors or developed internally, but regardless of their source, there are numerous considerations for their reliable long-term use.

New setting for the Land O'Lakes Bioanalytical Conference.

The University of Wisconsin bioanalytical conference is presented each year by the Extension Services in Pharmacy, the professional development department within the School of Pharmacy. The purpose of this 3-day conference was to provide an educational forum to discuss issues and applications associated with the analysis of xenobiotics, metabolites, biologics and biomarkers in biological matrices. The conference was designed to include and encourage an open exchange of scientific and methodological applications for bioanalysis.

Target-mediated drug disposition and prolonged liver accumulation of a novel humanized anti-CD81 monoclonal antibody in cynomolgus monkeys.

CD81 is an essential receptor for hepatitis C virus (HCV). K21 is a novel high affinity anti-CD81 antibody with potent broad spectrum anti-HCV activity in vitro. The pharmacokinetics (PK), pharmacodynamics and liver distribution of K21 were characterized in cynomolgus monkeys after intravenous (i.

High-throughput phagocytosis assay utilizing a pH-sensitive fluorescent dye.

We describe a development of a novel high-throughput phagocytosis assay based on a pH-sensitive cyanine dye, CypHer5E, which is maximally fluorescent in an acidic environment. This dye is ideally suited for the study of phagocytosis because of the acidic conditions generated in the intracellular phagocytic vesicles after particle uptake. Use of CypHer5E-labeled particles results in greatly reduced background from noninternalized particles and makes the assay more robust.

Unique architecture of the plastid ribosomal RNA operon promoter recognized by the multisubunit RNA polymerase in tobacco and other higher plants.

Expression of the plastid rRNA operon (rrn) during development is highly regulated at the level of transcription. The plastid rrn operon in most higher plants is transcribed by the plastid-encoded RNA polymerase (PEP), the multisubunit plastid RNA polymerase from PrrnP1, a sigma(70)-type promoter with conserved -10 and -35 core promoter elements. To identify functionally important sequences, the tobacco PrrnP1 was dissected in vivo and in vitro.

Epigenetic inhibition of lysyl oxidase transcription after transformation by ras oncogene.

Lysyl oxidase is an extracellular enzyme involved in connective tissue maturation that also acts as a phenotypic suppressor of the ras oncogene. To understand how this suppressor is controlled, gene transcription was studied and the promoter was characterized. Nuclear runoff transcription assays indicated that the markedly reduced amounts of lysyl oxidase message detected after ras transformation resulted from inhibition of lysyl oxidase transcription.

The phage-type PclpP-53 plastid promoter comprises sequences downstream of the transcription initiation site.

The existence of a phage-type plastid transcription machinery (NEP), related to the mitochondrial RNA polymerase, has been recognized only recently. Here we report the cis sequences required for transcription initiation by the phage-type enzyme. The promoter chosen for the study, PclpP-53, is well expressed in tobacco leaves, unlike most NEP promoters.

Transcription from heterologous rRNA operon promoters in chloroplasts reveals requirement for specific activating factors.

The plastid rRNA (rrn) operon in chloroplasts of tobacco (Nicotiana tabacum), maize, and pea is transcribed by the plastid-encoded plastid RNA polymerase from a sigma70-type promoter (P1). In contrast, the rrn operon in spinach (Spinacia oleracea) and mustard chloroplasts is transcribed from the distinct Pc promoter, probably also by the plastid-encoded plastid RNA polymerase. Primer-extension analysis reported here indicates that in Arabidopsis both promoters may be active.