Advances in Targeted Therapy: Addressing Resistance to BTK Inhibition in B-Cell Lymphoid Malignancies.

B-cell lymphoid malignancies are a heterogeneous group of hematologic cancers, where Bruton's tyrosine kinase (BTK) inhibitors have received FDA approval for several subtypes. The first-in-class covalent BTK inhibitor, Ibrutinib, binds to the C481 amino acid residue to block the BTK enzyme and prevent the downstream signaling. Resistance to covalent BTK inhibitors (BTKi) can occur through mutations at the BTK binding site (C481S) but also other BTK sites and the phospholipase C gamma 2 (PLCγ2) resulting in downstream signaling.

Pericardiocentesis Outcomes in Patients With Pulmonary Hypertension: A Nationwide Analysis from the United States.

Pericardiocentesis (PC) in patients with pulmonary hypertension (PH) and pericardial effusions has unclear benefits because it has been associated with acute hemodynamic collapse and increased mortality. Data on in-hospital outcomes in this population are limited. The National Inpatient Sample database was used to identify adult patients who underwent PC during hospitalizations between 2016 and 2020.

3D Bioprintable Hydrogel with Tunable Stiffness for Exploring Cells Encapsulated in Matrices of Differing Stiffnesses.

In vitro cell models have undergone a shift from 2D models on glass slides to 3D models that better reflect the native 3D microenvironment. 3D bioprinting promises to progress the field by allowing the high-throughput production of reproducible cell-laden structures with high fidelity. The current stiffness range of printable matrices surrounding the cells that mimic the extracellular matrix environment remains limited.

Post-functionalization of drug-loaded nanoparticles prepared by polymerization-induced self-assembly (PISA) with mitochondria targeting ligands.

Herein, the postfunctionalization of different non-fouling PISA particles, prepared from either poly(oligo ethylene glycol methyl ether methacrylate) (pPEGMA) and the anticancer drug PENAO (4-(-(-penicillaminylacetyl)amino)phenylarsenonous acid) or zwitterionic 2-methacryloyloxyethyl phosphorylcholine (MPC) and PENAO were reported. Both PISA particles were reacted with triphenylphosphonium (TPP) as mitochondria targeting units in order to evaluate the changes in cellular uptake or the toxicity of the conjugated arsenic drug. Attachment of TPP onto the PISA particles however was found not to enhance the mitochondrial accumulation, but it did influence overall the biological activity of pMPC-based particles in 2D and 3D cultured sarcoma SW982 cells.

Direct Comparison of Poly(ethylene glycol) and Phosphorylcholine Drug-Loaded Nanoparticles In Vitro and In Vivo.

Phosphorylcholine is known to repel the absorption of proteins onto surfaces, which can prevent the formation of a protein corona on the surface of nanoparticles. This can influence the fate of nanoparticles used for drug delivery. This material could therefore serve as an alternative to poly(ethylene glycol) (PEG).