Effect of cyclo-oxygenase inhibitor use during checkpoint blockade immunotherapy in patients with metastatic melanoma and non-small cell lung cancer.

Background: Immune checkpoint inhibitors (ICIs) improve survival outcomes in metastatic melanoma and non-small cell lung cancer (NSCLC). Preclinical evidence suggests that overexpression of cyclo-oxygenase-2 (COX2) in tumors facilitates immune evasion through prostaglandin E2 production and that COX inhibition synergizes with ICIs to promote antitumor T-cell activation. This study investigates whether concurrent COX inhibitor (COXi) use during ICI treatment compared with ICI alone is associated with improved time-to-progression (TTP), objective response rate (ORR) and overall survival (OS) in patients with metastatic melanoma and NSCLC.

Quantitative comparison of tumor delivery for multiple targeted nanoparticles simultaneously by multiplex ICP-MS.

Given the rapidly expanding library of disease biomarkers and targeting agents, the number of unique targeted nanoparticles is growing exponentially. The high variability and expense of animal testing often makes it unfeasible to examine this large number of nanoparticles in vivo. This often leads to the investigation of a single formulation that performed best in vitro.

ICP-MS analysis of lanthanide-doped nanoparticles as a non-radiative, multiplex approach to quantify biodistribution and blood clearance.

Recent advances in material science and chemistry have led to the development of nanoparticles with diverse physicochemical properties, e.g. size, charge, shape, and surface chemistry.

pH-titratable superparamagnetic iron oxide for improved nanoparticle accumulation in acidic tumor microenvironments.

A wide variety of nanoparticle platforms are being developed for the diagnosis and treatment of malignancy. While many of these are passively targeted or rely on receptor-ligand interactions, metabolically directed nanoparticles provide a complementary approach. It is known that both primary and secondary events in tumorigenesis alter the metabolic profile of developing and metastatic cancers.

Conformation of the Group II intron branch site in solution.

Group II introns are multidomain ribozymes that catalyze their own removal from pre-mRNA. The nucleophile for the first cleavage step is the 2'OH of a specific adenosine within domain 6 (D6), called the branch site. Mechanistic parallels and limited secondary structural similarity with the eukaryotic spliceosome lead many to speculate that the two systems have a common ancestry.