The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signalling pathway is one of the most important in transducing signals from the cell surface to the nucleus in response to cytokines. In the present study, we investigated chronological alteration and cellular location of JAK1, STAT3, phosphorylated (p)-Tyr1022/1023-JAK1, p-Tyr705-STAT3, and interleukin-6 (IL-6) following spinal cord injury (SCI) in mice. Western blot analysis showed JAK1 to be significantly phosphorylated at Tyr1022/1023 from 6 h after SCI, peaking at 12 h and gradually decreasing thereafter, accompanied by phosphorylation of STAT3 at Tyr705 with a similar time course. ELISA analysis showed the concentration of IL-6 in injured spinal cord to also significantly increase from 3 h after SCI, peaking at 12 h, then gradually decreasing. Immunohistochemistry revealed p-Tyr1022/1023-JAK1, p-Tyr705-STAT3, and IL-6 to be mainly expressed in neurons of the anterior horns at 12 h after SCI. Pretreatment with a JAK inhibitor, AG-490, suppressed phosphorylation of JAK1 and STAT3 at 12 h after SCI, reducing recovery of motor functions. These findings suggest that SCI at the acute stage produces IL-6 mainly in neurons of the injured spinal cord, which activates the JAK/STAT pathway, and that this pathway may be involved with neuronal response to SCI. Keywords: interleukin-6, Janus kinase 1, phosphorylation, signal transducer and activator of transcription 3, spinal cord injury.

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Transfer of interferon beta gene via cationic liposomes has been found to induce regression of experimental glioma. We performed a pilot clinical trial of safety and effectiveness of this interferon beta gene therapy in five patients with malignant glioma (glioblastoma multiforme or anaplastic astrocytoma). Transgene expression and antitumor activity were detected in four patients. Two patients showed a partial response (>50% tumor reduction) and two others had stable disease 10 weeks after beginning therapy. One patient could not be evaluated because of previous treatment with gamma-knife therapy. This study suggests the feasibility and safety of interferon beta gene therapy, which may become an important treatment option for patients with malignant glioma.

Gefitinib--a specific inhibitor of epidermal growth factor receptor (EGFR)-associated tyrosine kinase--has demonstrated efficacy in a subgroup of patients with non-small-cell lung carcinoma (NSCLC) who fail conventional chemotherapy. It is also reported to have an antitumor effect in brain metastases from NSCLC. Additionally, EGFR mutations have shown a strong association with gefitinib sensitivity for NSCLC. Here, we assessed the efficacy of gefitinib in brain metastases from NSCLC and evaluated the association of this efficacy with EGFR mutations. We retrospectively reviewed eight cases in which patients were suffering from brain metastases before the initiation of gefitinib treatment. Brain tumor response could be evaluated by MRI in these patients; EGFR gene analyses were also available. We evaluated whether objective tumor response was observed after gefitinib treatment and assessed the efficacy of gefitinib as effective, noneffective, or not assessable in consideration of the influence of previous radiotherapy. Of the eight patients, the efficacy of gefitinib was assessed as effective in three and as noneffective in three. All three patients demonstrating effective efficacy had EGFR mutations in the tyrosine kinase domain (deletion mutation in two patients and point mutation in one patients), whereas none of the three patients demonstrating noneffective efficacy had EGFR mutations. Gefitinib appears to be effective in treating brain metastases in a subgroup of patients. Our data suggested a possible association between the efficacy of gefitinib in the treatment of brain metastases and EGFR mutations.