The performance of three oncogeriatric screening tools - G8, optimised G8 and CARG - in predicting chemotherapy-related toxicity in older patients with cancer. A prospective clinical study.

Background: Older patients are vulnerable to chemotherapy-related toxicity (CRT). Therefore we evaluated screening tools in their power to predict CRT.

Methods: Patients with cancer aged ≥65 years completed three screening questionnaires (G8, optimised G8 and Cancer and Ageing Research Group (CARG).

Tie2 as a novel key factor of microangiopathy in systemic sclerosis.

Background: The angiopoietin(Ang)/Tie2 system is a key regulator of vascular biology. The expression of membrane bound (mb) Tie2 and Ang-1 ensures vessel stability, whereas Ang-2, inducible by vascular endothelial growth factor (VEGF), hypoxia, and inflammation, acts as an antagonist. Tie2 signalling is also attenuated by soluble Tie2 (sTie2), the extracellular domain of the receptor, which is shed upon stimulation with VEGF.

Trichostatin A prevents the accumulation of extracellular matrix in a mouse model of bleomycin-induced skin fibrosis.

Objective: Tissue fibrosis is a hallmark compromising feature of many disorders. In this study, we investigated the antifibrogenic effects of the histone deacetylase inhibitor trichostatin A (TSA) on cytokine-driven fibrotic responses in vitro and in vivo.

Methods: Skin fibroblasts from patients with systemic sclerosis (SSc) and normal healthy control subjects were stimulated with profibrotic cytokines in combination with TSA.

Histone deacetylase/acetylase activity in total synovial tissue derived from rheumatoid arthritis and osteoarthritis patients.

Objective: Rheumatoid arthritis (RA) is a chronic inflammatory disorder of unknown origin. Histone deacetylase (HDA) activity is considered to play a major role in the transcriptional regulation of proinflammatory genes. We undertook this study to investigate the balance of histone acetylase and HDA activity in synovial tissue from RA patients compared with that from patients with osteoarthritis (OA) and normal controls.

The role of membrane lipids in the induction of macrophage apoptosis by microparticles.

Microparticles are membrane-derived vesicles that are released from cells during activation or cell death. These particles can serve as mediators of intercellular cross-talk and induce a variety of cellular responses. Previous studies have shown that macrophages undergo apoptosis after phagocytosing microparticles.

Technology insight: gene transfer and the design of novel treatments for rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by systemic inflammation and joint destruction. Novel therapies have emerged during the past decade, marking a new era in the treatment of RA. Meanwhile, in vivo and in vitro gene-transfer studies have provided valuable insights into mechanisms of disease pathogenesis.

Ex vivo homeostatic proliferation of CD4+ T cells in rheumatoid arthritis is dysregulated and driven by membrane-anchored TNFalpha.

The systemic CD4(+) T cell compartment in patients with rheumatoid arthritis (RA) is characterized by TCR repertoire contraction, shortened telomere lengths, and decreased numbers of recent thymic emigrants, suggesting a disturbed CD4(+) T cell homeostasis. In mice, homeostatic proliferation of peripheral CD4(+) T cells is regulated by TCR interaction with self peptide-MHC complexes (pMHC) and can be reproduced in vitro. We have established an ex vivo model of homeostatic proliferation, in which self-replication of human CD4(+) T cells is induced by cell-cell contact with autologous monocytes.