Altered expression of cell proliferation-related and interferon-stimulated genes in colon cancer cells resistant to SN38.

Irinotecan is a topoisomerase I inhibitor widely used as an anticancer agent in the treatment of metastatic colon cancer. However, its efficacy is often limited by the development of resistance. We have isolated a colon carcinoma cell line, HCT116-SN6, which displays a 6-fold higher resistance to SN38, the active metabolite of irinotecan.

ABCG2 overexpression in colon cancer cells resistant to SN38 and in irinotecan-treated metastases.

Overcoming drug resistance has become an important issue in cancer chemotherapy. Among all known mechanisms that confer resistance, active efflux of chemotherapeutic agents by proteins from the ATP-binding cassette family has been extensively reported. The aim of the present study was to determine the involvement of ABCG2 in resistance to SN38 (the active metabolite of irinotecan) in colorectal cancer.

Human Th2-like cell clones induce IL-12 production by dendritic cells and may express several cytokine profiles.

Previous studies have shown that human Th2 cells, unlike their murine counterparts, retain the ability to produce IFN-gamma upon activation in the presence of exogenous IL-12. Here we first extended this notion by showing that Th2-like cell clones (Th2C) are also capable of inducing IL-12 production by physiological antigen-presenting cells (APC); we next showed that these cells may express several distinct cytokine profiles depending upon the activation signal and the type of APC with which they interact. We have analyzed the production of IL-4, IL-5 and IFN-gamma by Th2C stimulated by either anti-CD3 mAb or exogenous IL-2, using peripheral blood monocytes or dendritic cells (DC) as accessory cells.

CD31 (PECAM-1) is a differentiation antigen lost during human CD4 T-cell maturation into Th1 or Th2 effector cells.

The CD31 antigen (PECAM-1) has been reported to be a stable marker for a human CD4 T-cell subpopulation unable to produce interleukin-4 (IL-4). We show here that CD31 expression is not stable inasmuch as CD4 T-cell lines and clones derived from cell-sorted neonatal CD31+ cells lose CD31 upon repetitive cycles of stimulation and IL-2 expansion. Moreover, various cytokines (IL-1 alpha, IL-4, IL-6, transforming growth factor-beta) fail to reinduce CD31 on CD31- clones.

Maturation of neonatal human CD4 T cells: III. Role of B7 co-stimulation at priming.

We previously reported that human naive CD4 T cells differentiate into effector cells producing type 1 (IL-2, IFN-gamma) and type 2 (IL-4, IL-5, IL-10) cytokines after priming with anti-CD3 mAb presented on irradiated CD32-transfected mouse L fibroblasts, in the absence of exogenous cytokine. Here we first show that the CD32 L fibroblasts act not only by cross-linking anti-CD3 mAb but also by providing a B7-mediated co-stimulation signal which is required for the activation of naive T cells. Using a selected anti-CD3 mAb (64.