The transcription factor nuclear factor-kB (NF-kB) regulates genes important for tumor invasion, metastasis and chemoresistance. Normally, NF-kB remains sequestered in an inactive state by cytoplasmic inhibitor-of-kB (IkB) proteins. NF-kB translocates to nucleus and activates gene expression upon exposure of cells to growth factors and cytokines. We and others have shown previously that NF-kB is constitutively active in a subset of breast cancers. In this study, we show that constitutive activation of NF-kB leads to overexpression of the antiapoptotic genes c-inhibitor of apoptosis 2 (c-IAP2) and manganese superoxide dismutase (Mn-SOD) in breast cancer cells. Furthermore, expression of the antiapoptotic tumor necrosis factor receptor associated factor 1 (TRAF1) and defender-against cell death (DAD-1) is regulated by NF-kB in certain breast cancer cells. We also demonstrate that NF-kB-inducible genes protect cancer cells against paclitaxel as MDA-MB-231 breast cancer cells modi®ed to overexpress IkBa required lower concentrations of paclitaxel to arrest at the G2/M phase of the cell cycle and undergo apoptosis when compared to parental cells. The eect of NF-kB on paclitaxel-sensitivity appears to be speci®c to cancer cells because normal ®broblasts derived from embryos lacking p65 subunit of NF-kB and wild type littermate embryos were insensitive to paclitaxel-induced G2/M cell cycle arrest. Parthenolide, an active ingredient of herbal remedies such as feverfew (tanacetum parthenium), mimicked the eects of IkBa by inhibiting NF-kB DNA binding activity and Mn-SOD expression, and increasing paclitaxel-induced apoptosis of breast cancer cells. These results suggest that active ingredients of herbs with anti-in¯ammatory properties may be useful in increasing the sensitivity of cancers with constitutively active NF-kB to chemotherapeutic drugs. Oncogene (2000) 19, 4159 ± 4169.

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Based on 5-HTT occupancy, 40 mg and more of duloxetine was needed to attain 80% occupancy, and 60 mg of duloxetine could maintain a high level of 5-HTT occupancy with a once-a-day administration schedule.

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Systematic review of observational studies has revealed that fish consumption and levels of n-3 polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid are associated with a reduced risk of depression. A reverse J-shaped effect of n-3 PUFAs was suggested. However, there is limited evidence from populations with high fish consumption and no studies have used a standard psychiatrist-based diagnosis of major depressive disorder (MDD). Therefore, this population-based, prospective study investigated the association of dietary fish, n-3 PUFA, and n-6 PUFA consumption with risk of psychiatrist-diagnosed MDD in Japan. A total of 12 219 subjects were enrolled from the Saku area in 1990. Of these, we extracted 1181 participants aged 63–82 years who completed food frequency questionnaires in both 1995 and 2000 and also underwent a mental health examination in 2014–2015. Odds ratios (ORs) and 95% confidence intervals (CIs) for MDD according to fish intake and PUFA quartiles were calculated. Current MDD was diagnosed in 95 patients. We found a reduced risk of MDD in the third quartile for fish intake (111.1 g per day, OR=0.44, 95% CI=0.23–0.84), second quartile for EPA (307.7 mg per day, OR=0.54, 95% CI=0.30–0.99) and third quartile for docosapentaenoic acid (DPA) (123.1 mg per day, OR=0.42, 95% CI=0.22–0.85). ORs adjusted for cancer, stroke, myocardial infarction and diabetes remained significant for fish and DPA intake. Our results suggest that moderate fish intake could be recommended for the prevention of MDD in aged Japanese individuals.