Spatial Mapping and Immunomodulatory Role of the OX40/OX40L Pathway in Human Non-Small Cell Lung Cancer.

Purpose: To evaluate the tissue distribution and clinical significance of OX40 and OX40L in human non-small cell lung cancer (NSCLC).

Experimental Design: Using multiplexed quantitative immunofluorescence, we conducted simultaneous and localized measurements of OX40 and OX40L proteins, major T-cell subsets, and conventional type 1 dendritic cells (cDC1) in 614 primary NSCLCs from three independent cohorts represented in tissue microarrays. We also measured OX40L protein in samples from a phase I clinical trial of intratumor administration of a lipid nanoparticle encapsulated mRNA encoding OX40L (mRNA-2416) in human solid tumors.

Differential immunomodulatory effect of PARP inhibition in BRCA1 deficient and competent tumor cells.

Poly-ADP-ribose polymerase (PARP) inhibitors are active against cells and tumors with defects in homology-directed repair as a result of synthetic lethality. PARP inhibitors (PARPi) have been suggested to act by either catalytic inhibition or by PARP localization in chromatin. In this study, we treat BRCA1 mutant cells derived from a patient with triple negative breast cancer and control cells for three weeks with veliparib, a PARPi, to determine if treatment with this drug induces increased levels of mutations and/or an inflammatory response.

The impact of supine hypertension on target organ damage and survival in patients with synucleinopathies and neurogenic orthostatic hypotension.

Introduction: In addition to neurogenic orthostatic hypotension (nOH), patients with synucleinopathies frequently have hypertension when supine. The long-term consequences of both abnormalities are difficult to disentangle. We aimed to determine if supine hypertension is associated with target organ damage and worse survival in patients with nOH.

Burnout Syndrome in Family Health Strategy Managers.

This paper analyzed the Burnout Syndrome (BS) among the managers of the Family Health Strategy (ESF) in the city of Rio de Janeiro and its associations with factors that influence the presence/absence of BS among these professionals. This is a descriptive study that used data from a questionnaire consisting of two parts: 1) manager profile and factors that could influence the presence of Burnout; 2) Maslach Burnout Inventory. The return rate was 63.

Uncoupling the Senescence-Associated Secretory Phenotype from Cell Cycle Exit via Interleukin-1 Inactivation Unveils Its Protumorigenic Role.

Cellular senescence has emerged as a potent tumor suppressor mechanism in numerous human neoplasias. Senescent cells secrete a distinct set of factors, collectively termed the senescence-associated secretory phenotype (SASP), which has been postulated to carry both pro- and antitumorigenic properties depending on tissue context. However, the effect of the SASP is poorly understood due to the difficulty of studying the SASP independently of other senescence-associated phenotypes.