Th17 cells in multiple sclerosis express higher levels of JAK2, which increases their surface expression of IFN-γR2.

IFN-β inhibits the expansion of Th17 cells in active multiple sclerosis (AMS), and this might contribute to improve the clinical symptoms. The effectiveness of this inhibition, however, requires intact IFN-γ signaling in T cells. In this study, we report that both mRNA and cell surface expression of the signaling chain of the IFN-γ receptor (IFN-γR2) and its cognate tyrosine kinase JAK2 are enhanced in peripheral blood Th17 cells and clones from patients with AMS compared with those with inactive multiple sclerosis (IMS) or healthy subjects (HS).

Synergistic antitumor activity of sorafenib in combination with epidermal growth factor receptor inhibitors in colorectal and lung cancer cells.

Purpose: Cancer cell survival, invasion, and metastasis depend on cancer cell proliferation and on tumor-induced angiogenesis. We evaluated the efficacy of the combination of sorafenib and erlotinib or cetuximab.

Experimental Design: Sorafenib, erlotinib, and cetuximab, alone or in combination, were tested in vitro in a panel of non-small cell lung cancer (NSCLC) and colorectal cancer cell lines and in vivo in H1299 tumor xenografts.

beta(3) Integrin subunit mediates the bone-resorbing function exerted by cultured myeloma plasma cells.

alpha(v)beta(3) integrin was investigated in multiple myeloma in relation to the in vitro osteoclast-like activity of malignant plasma cells. Myeloma cells from patients with skeleton involvement overexpressed alpha(v)beta(3) and produced erosion pits on bone substrates, whereas this effect was not observed by cells from patients with no evidence of bone disease. We therefore explored the alpha(v)beta(3) transcriptional pathway in the bone-resorbing cells.

Human interleukin 17-producing cells originate from a CD161+CD4+ T cell precursor.

We demonstrate that CD161 is a highly up-regulated gene in human interleukin (IL) 17 T helper cell (Th17) clones and that all IL-17-producing cells are contained in the CD161(+) fraction of CD4(+) T cells present in the circulation or in inflamed tissues, although they are not CD1-restricted natural killer T cells. More importantly, we show that all IL-17-producing cells originate from CD161(+) naive CD4(+) T cells of umbilical cord blood, as well as of the postnatal thymus, in response to the combined activity of IL-1 beta and IL-23. These findings implicate CD161 as a novel surface marker for human Th17 cells and demonstrate the exclusive origin of these cells from a CD161(+)CD4(+) T cell progenitor.

Synergistic anti-proliferative and pro-apoptotic activity of combined therapy with bortezomib, a proteasome inhibitor, with anti-epidermal growth factor receptor (EGFR) drugs in human cancer cells.

The proteasome plays a pivotal role in the turnover of regulatory transduction proteins induced by activated cell membrane growth factor receptors. The epidermal growth factor receptor (EGFR) pathway is crucial in the development and progression of human epithelial cancers. Proteasome inhibition may sensitize human cancer cell lines to EGFR inhibitors.

Myocardial strain analysis in a doxorubicin-induced cardiomyopathy model.

The aim of our study was to determine if strain (S) and strain rate (SR) imaging are more sensitive indices with respect to standard echocardiographic parameters to assess cardiac function in an experimental model of doxorubicin (DOX)-induced cardiomyopathy. DOX was administered intraperitoneally 4x/wk at the dose of 1.25 mg/kg/d over four weeks in Wistar rats (n = 26).