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5 result(s) for "Hakozaki, Nozomi"
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Helicobacter pylori, Homologous-Recombination Genes, and Gastric Cancer
Infection with Helicobacter pylori is known to confer a risk of gastric cancer. In this study, persons who carried certain genetic variants and were infected with H. pylori had an excess risk of gastric cancer.
Prognostic significance of pathogenic variants in BRCA1, BRCA2, ATM and PALB2 genes in men undergoing hormonal therapy for advanced prostate cancer
BackgroundThe prognostic significance of germline variants in homologous recombination repair genes in advanced prostate cancer (PCa), especially with regard to hormonal therapy, remains controversial.MethodsGermline DNA from 549 Japanese men with metastatic and/or castration-resistant PCa was sequenced for 27 cancer-predisposing genes. The associations between pathogenic variants and clinical outcomes were examined. Further, for comparison, DNA from prostate biopsy tissue samples from 80 independent patients with metastatic PCa were analysed.ResultsForty-four (8%) patients carried germline pathogenic variants in one of the analysed genes. BRCA2 was most frequently altered (n = 19), followed by HOXB13 (n = 9), PALB2 (n = 5) and ATM (n = 5). Further, the BRCA1, BRCA2, PALB2 and ATM variants showed significant association with a short time to castration resistance and overall survival (hazard ratio = 1.99 and 2.36; 95% CI, 1.15–3.44 and 1.23–4.51, respectively), independent of other clinical variables. Based on log-rank tests, the time to castration resistance was also significantly short in patients with BRCA1, BRCA2, PALB2 or ATM somatic mutations and TP53 mutations.ConclusionsGermline variants in BRCA1, BRCA2, PALB2 or ATM are independent prognostic factors of the short duration of response to hormonal therapy in advanced PCa.
Nrf2 Activation by 5-lipoxygenase Metabolites in Human Umbilical Vascular Endothelial Cells
5-hydroxyeicosatetraenoic acid (5-HETE) and 5-hydroxyeicosapentaenoic acid (5-HEPE) are major metabolites produced by 5-lipoxygenase (5-LOX) from arachidonic acid (AA) and eicosapentaenoic acid (EPA). Effects of hydroxides on endothelial cells are unclear, although 5-LOX is known to increase at arteriosclerotic lesions. To investigate the effects of hydroxides on human umbilical vein endothelial cells (HUVECs), the cells were treated with 50 μM each of AA, EPA, 5-HETE, and 5-HEPE. Treatment of HUVECs with 5-HETE and 5-HEPE, rather than with AA and EPA, increased the nuclear translocation of NF-E2 related factor 2 (Nrf2) and upregulated the expression of heme oxygenase-1 and cystine/glutamate transporter regulated by Nrf2. Reactive oxygen species (ROS) generation was markedly elevated in HUVECs after treatment with 5-HETE and 5-HEPE, and the pretreatment with α-tocopherol abrogated ROS levels similar to those in the vehicle control. However, ROS generation was independent of Nrf2 activation induced by 5-HETE and 5-HEPE. 5-HETE was converted to 5-oxo-eicosatetraenoic acid (5-oxo-ETE) in HUVECs, and 5-oxo-ETE increased Nrf2 activation. These results suggest that 5-HETE works as an Nrf2 activator through the metabolite 5-oxo-ETE in HUVECs. Similarly, 5-HEPE works in the same way, because 5-HEPE is metabolized to 5-oxo-eicosapentaenoic acid through the same pathway as that for 5-HETE.
Lipids, fatty acids and hydroxy-fatty acids of Euphausia pacifica
Euphausia pacifica is a good candidate for a resource of marine n-3 PUFA. However, few reports exist of the lipid and fatty acid composition of E. pacifica . To examine the potential of E. pacifica as a resource of marine n-3 PUFA, we analyzed E. pacifica oil. We extracted lipids from E. pacifica harvested from the Pacific Ocean near Sanriku, Japan. Lipid classes of E. pacifica oil were analyzed by TLC-FID and the fatty acid composition of the oil was analyzed by GC/MS. Free fatty acids and hydroxy-fatty acids were analyzed by LC/QTOFMS. The lipid content of E. pacifica ranged from 1.30% to 3.57%. The ratios of triacylglycerols, phosphatidylcholine, phosphatidylethanolamine and free fatty acids in E. pacifica lipids were 5.3–23.0%, 32.6–53.4%, 8.5–25.4% and 2.5–7.0%, respectively. The content of n-3 PUFA in E. pacifica lipids was 38.6–46.5%. We also showed that E. pacifica contains unusual fatty acids and derivatives: C16-PUFAs (9,12-hexadecadienoic acid, 6,9,12-hexadecatrienoic acid and 6,9,12,15-hexadecatetraenoic acid) and hydroxy-PUFAs (8-HETE and 10-HDoHE). E. pacifica is a good resource of marine n-3 PUFA. Moreover, E. pacifica can provide C16-PUFA and hydroxy-PUFAs.