BACKGROUND: Signal transducer and activator of transcription 3 (STAT3) regulates the expression of genes that mediate cell survival, proliferation, and angiogenesis and is aberrantly activated in various types of malignancies, including renal cell carcinoma (RCC). We examined whether it could be a novel therapeutic target for RCC by using the STAT3 inhibitor WP1066. METHODS: The antitumour activities and related mechanisms of WP1066 were investigated in vitro on renal cancer cell lines and in vivo on murine xenografts. RESULTS: In Caki-1 and 786-O renal cancer cells, 5 mM WP1066 prevented the phosphorylation of STAT3, and 2.5 mM WP1066 significantly (Po0.01) inhibited cell survival and proliferation. WP1066 suppressed the expression of Bcl-2, induced apoptosis, and inhibited the basal and hypoxia-induced expression of HIF1a and HIF2a, as well as vascular endothelial growth factor secretion into cell culture medium. Human umbilical vascular endothelial cells cocultured with media from WP1066-treated cells showed significantly reduced tubulogenesis (Po0.05). Systemic oral administration of WP1066 to mice for 19 days significantly inhibited the growth of Caki-1 xenograft tumours (Po0.05), and pathological analysis of xenografts of WP1066-treated mice showed decreased immunostaining of phosphorylated STAT3 and reduced length of CD34-positive vessels (Po0.05). CONCLUSIONS: Our results suggest that using WP1066 to inhibit the STAT3 signalling pathway could be a novel therapeutic strategy against RCC.

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The present findings coincide with our hypothesis that circulating mtDNA contributes to the inflammation in MDD. Further studies are needed to conclude whether plasma mtDNA would be a biomarker of mood disorders.

While DOC did not affect PSMA expression, it was unexpectedly found to down-regulate AR and PSA. DOC-induced down-regulation of AR might be one of the anti-tumor mechanisms active in PC. Down-regulation of PSA may account for the significantly higher PSA response rates (45-50%) relative to measurable response rates (8-17%) reported in DOC PC trials and have implications for PSA surrogacy observations derived from DOC trials.

Neurotrophins such as the brain-derived neurotrophic factor (BDNF) are reportedly related to the pathogenesis of Alzheimer's disease (AD). Several studies have revealed an alteration in BDNF expression in the postmortem brains of AD patients. BDNF has great potential as a therapeutic agent because of its ability to cross the blood-brain barrier and due to its wide in vivo distribution. However, little is known about in vivo BDNF in dementia patients. Moreover, the immunological function of neurotrophins such as BDNF has received great interest. Therefore, we investigated the serum levels of BDNF and cytokines such as TNF-alpha and IL-1beta in dementia patients by the enzyme-linked immunosorbent assay (ELISA). The following subjects were included in this study: 60 AD patients, 60 vascular dementia (VaD) patients and 33 healthy controls. AD and VaD patients were matched for age, gender and severity of dementia. Serum BDNF levels in AD patients were significantly lower than those in VaD patients and controls. TNF-alpha and IL-1beta levels showed no significant difference among the three groups. In the dementia groups, neither the TNF-alpha nor the IL-1beta levels correlated with the BDNF levels. Our results suggest that BDNF may play a pathological role in some cases of AD.

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Purpose: To investigate the prevalence of cervical and intracranial atherosclerosis and silent brain infarction in patients with coronary artery disease (CAD). Methods: Cervical and intracranial atherosclerotic lesions on magnetic resonance angiography (MRA) and silent brain infarctions on magnetic resonance imaging (MRI) were investigated in comparison with the findings of coronary angiography in 133 consecutive patients with CAD. Results: The mean severity scores of cervical and intracranial MRA lesions were significantly higher in the three-vessel CAD (0.40 and 0.53, respectively) than in the zero-vessel CAD group (0.04 and 0.11). The mean scores of the maximal size and multiplicity of MRI lesion were also significantly greater in the two-vessel (1.00 and 1.44) and three-vessel CAD (0.94 and 1.26) than in the zero-vessel CAD group (0.27 and 0.50). The incidence of MRA lesion was markedly higher in patients with brain MRI lesion than in those without (51.1 vs. 6.5%). Conclusions: Serious coronary artery lesions were commonly accompanied by latent atherosclerotic lesions in the cervical and intracranial arteries besides silent brain infarction in patients with CAD.

Public health nurses visited and followed up for more than one year 438 patients with Parkinson's disease living in Osaka. The follow-up period averaged 4.1 years, during which 71 deaths were observed. The patients were classified according to the degree of physical exercise they performed, and the ratios of observed to expected deaths were calculated. The exercising group showed the lowest ratio of 1.68 (1.45 for patients able to walk independently, and 1.89 for those could not) while all patients exhibited a ratio of 2.47. Multivariate analysis using Cox's proportional hazard model, adjusted for age, sex, walking ability and duration of disease at study entry, showed that, compared with the exercising group, the non-exercising patients had a hazard ratio of 1.83.