Non-core region modulates interleukin-11 signaling activity: generation of agonist and antagonist variants.

Human interleukin-11 (hIL-11) is a pleiotropic cytokine administered to patients with low platelet counts. From a structural point of view hIL-11 belongs to the long-helix cytokine superfamily, which is characterized by a conserved core motif consisting of four α-helices. We have investigated the region of hIL-11 that does not belong to the α-helical bundle motif, and that for the purpose of brevity we have termed "non-core region.

Gene expression profiling predicts response to temozolomide in malignant gliomas.

Malignant gliomas are highly lethal neoplasms that cannot be cured with currently available therapies. Temozolomide (TMZ) is a recently introduced alkylating agent that has yielded significant benefits and become a key agent in the treatment of high-grade gliomas. However, its survival benefit remains unsatisfactory.

Effect of IFN-beta on human glioma cell lines with temozolomide resistance.

Human interferon-beta (IFN-beta) is known to exhibit pleiotropic biological activities including antitumor effects. On the other hand, temozolomide (TMZ), an oral bioavailable alkylating agent with excellent tolerability, has demonstrated efficacy and has become a key therapeutic agent in patients with malignant gliomas; however, its survival benefit remains unsatisfactory. More recent studies have indicated that there might be favorable therapeutic interactions between IFN-beta and TMZ, although the therapeutic advantages of such a combination have not yet been fully explored.

A possible role of autogenous IFN-beta for cytokine productions in human fibroblasts.

It has been already known that human diploid fibroblasts are able to produce not only high levels of IFN-beta but also various kinds of cytokines by poly rI: poly rC, and some inflammatory cytokines are induced by IFN-beta gene activation. We also obtained similar results. However, in our system, cytokine productions were extremely enhanced by treating the cells with a low dose of type 1 IFN and the priming effects on cytokine productions were blocked by cycloheximide similar to those on IFN-beta productions.

[Research and development of interferons].

After interferon was discovered, it has passed in 50 years. It looks back upon the basic research which contributed to progress of clinical application in the meantime, and development of the various IFNs which made the large-scale clinical test possible.