Immunotherapy with check-point inhibitors (CPI) in adult malignancies: a protocol for the systematic review of the quality of economic analyses.

Background: Immuno-oncology, and in particular, check-point inhibitors (CPIs), have led to a paradigm shift in the field of cancer care. The cost of new drug development is high, and many novel agents in oncology are significantly more expensive than older agents. Therefore, healthcare funders have factored measures of cost-effectiveness into decisions concerning drug reimbursement and incorporation of new agents into treatment algorithms.

A Real-World Comparison of FOLFIRINOX, Gemcitabine Plus nab-Paclitaxel, and Gemcitabine in Advanced Pancreatic Cancers.

Purpose: FOLFIRINOX (FFN), nab-paclitaxel plus gemcitabine (GN), and gemcitabine are three systemic therapies that provide clinically meaningful benefit to patients with unresectable pancreatic cancer (UPC). There are no clinical trials that directly compare the efficacy of all three regimens. In this study, we aim to examine and compare the real-world effectiveness of these treatments.

Toll-Like Receptor 7/8 Ligand, S28463, Suppresses Ascaris suum-induced Allergic Asthma in Nonhuman Primates.

S28463 (S28), a ligand for Toll-like receptor 7/8, has been shown to have antiinflammatory properties in rodent models of allergic asthma. The principle goal of this study was to assess whether these antiinflammatory effects can also be observed in a nonhuman primate (NHP) model of allergic asthma. NHPs were sensitized then challenged with natural allergen, Ascaris suum extract.

Mouse Chromosome 4 Is Associated with the Baseline and Allergic IgE Phenotypes.

Regulation of IgE concentration in the blood is a complex trait, with high concentrations associated with parasitic infections as well as allergic diseases. A/J strain mice have significantly higher plasma concentrations of IgE, both at baseline and after ovalbumin antigen exposure, when compared to C57BL/6J strain mice. Our objective was to determine the genomic regions associated with this difference in phenotype.

Mapping of a chromosome 12 region associated with airway hyperresponsiveness in a recombinant congenic mouse strain and selection of potential candidate genes by expression and sequence variation analyses.

In a previous study we determined that BcA86 mice, a strain belonging to a panel of AcB/BcA recombinant congenic strains, have an airway responsiveness phenotype resembling mice from the airway hyperresponsive A/J strain. The majority of the BcA86 genome is however from the hyporesponsive C57BL/6J strain. The aim of this study was to identify candidate regions and genes associated with airway hyperresponsiveness (AHR) by quantitative trait locus (QTL) analysis using the BcA86 strain.

Secretory leukocyte protease inhibitor plays an important role in the regulation of allergic asthma in mice.

Secretory leukocyte protease inhibitor (SLPI) is an anti-inflammatory protein that is observed at high levels in asthma patients. Resiquimod, a TLR7/8 ligand, is protective against acute and chronic asthma, and it increases SLPI expression of macrophages in vitro. However, the protective role played by SLPI and the interactions between the SLPI and resiquimod pathways in the immune response occurring in allergic asthma have not been fully elucidated.

Polymorphisms in TOLL-like receptor genes and their roles in allergic asthma and atopy.

Allergic asthma is a chronic inflammatory disease of the lung airways cause by genetic and environmental factors. Two quantifiable phenotypes of this disease are airway hyperresponsiveness and atopy. TOLL-like receptors (TLRs) are a family of intracellular and cell surface receptors that can respond to pathogen associated molecular patterns involved in the pathogenesis of asthma.

Identification of novel chromosomal regions associated with airway hyperresponsiveness in recombinant congenic strains of mice.

Airway responsiveness is the ability of the airways to respond to bronchoconstricting stimuli by reducing their diameter. Airway hyperresponsiveness has been associated with asthma susceptibility in both humans and murine models, and it has been shown to be a complex and heritable trait. In particular, the A/J mouse strain is known to have hyperresponsive airways, while the C57BL/6 strain is known to be relatively refractory to bronchoconstricting stimuli.

Modulation of the allergic asthma transcriptome following resiquimod treatment.

Resiquimod is a compound belonging to the imidazoquinoline family of compounds known to signal through Toll-like receptor 7. Resiquimod treatment has been demonstrated to inhibit the development of allergen induced asthma in experimental models. The aim of the present study was to elucidate the molecular processes that were altered following resiquimod treatment and allergen challenge in a mouse model of allergic asthma.

Protein tyrosine phosphatases regulate asthma development in a murine asthma model.

Allergic asthma is a chronic inflammatory disease characterized by Th2-type inflammation. Although the cellular interactions are now well studied, the intracellular signaling involved in asthma development is still a developing field. Protein tyrosine kinases are one focus of such research and their inhibition shows improvement of asthmatic features.

Chronic asthma-induced airway remodeling is prevented by toll-like receptor-7/8 ligand S28463.

Rationale: Allergic asthma is a heterogeneous disease, the pathology of which is a result of improper immune responses to innocuous antigens. We and others have previously shown that one of the Toll-like receptor (TLR)-7/8 ligands, the synthetic compound S28463 (resiquimod, R-848), is able to inhibit acute allergic asthma in mice.

Objectives: Given that the efficiency of this pharmacologic compound against the smooth muscle mass increase and goblet cell hyperplasia that are characteristic of chronic allergic asthma has not been previously assessed, we investigated the ability of this compound to prevent these aspects of chronic airway remodeling.