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  • 1
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    Hepatocyte nuclear factor-1β (HNF-1β) promotes glucose uptake and glycolytic activity in ovarian clear cell carcinoma (2013)
    Wiley-Blackwell
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    Publication Date: 2013-09-18
    Description: Ovarian clear cell carcinoma (OCCC) is a morphologically and biologically distinct subtype of ovarian carcinomas that often arises in ovarian endometriosis. We previously reported that a unique carcinogenic environment, especially iron-induced oxidative stress in endometriotic cysts may promote development of OCCC. We also identified a gene expression profile characteristic of OCCC (the “OCCC signature”). This 320-gene OCCC signature is enriched in genes associated with stress response and sugar metabolism. However, the biological implication of this profile is unclear. In this study, we have focused on the biological role of the HNF-1β gene within the OCCC signature, which was previously shown to be overexpressed in OCCC. Suppression of HNF-1β in the HNF-1β-overexpressing human ovarian cancer cell line RMG2 using short hairpin RNA resulted in a significant increase in proliferation. It also facilitated glucose uptake, glycolytic activity, and lactate secretion along with increased expression of the glucose transporter-1 ( GLUT-1 ) gene and several key enzymes in the glycolytic process. Conversely, forced expression of HNF-1β in the serous ovarian cancer cell line, Hey, resulted in slowed cellular growth and repressed glycolytic activity. These data suggest that HNF-1β represses cell growth, and at the same time, it promotes aerobic glycolysis which is known as the “Warburg effect.” As the Warburg effect is regarded as a characteristic metabolic process in cancer which may contribute to cell survival under hypoxic conditions or in a stressful environment, overexpression of HNF-1β may play an inevitable role in the occurrence of OCCC in stressful environment. © 2013 Wiley Periodicals, Inc.
    Print ISSN: 0899-1987
    Electronic ISSN: 1098-2744
    Topics: Medicine
    Published by Wiley-Blackwell
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  • 2
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    Clinical features and prognostic impact of PRDM16 expression in adult acute myeloid leukemia (2017)
    Wiley-Blackwell
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    Publication Date: 2017-07-16
    Description: High PRDM16 (also known as MEL1 ) expression is a representative marker of acute myeloid leukemia (AML) with NUP98-NSD1 and is a significant predictive marker for poor prognosis in pediatric AML. However, the clinical features of adult AML with PRDM16 expression remain unclear. PRDM16 is highly homologous to MDS1/EVI1 , which is an alternatively spliced transcript of MECOM (also known as EVI1 ). We investigated PRDM16 expression in 151 AML patients, with 47 (31%) exhibiting high PRDM16 expression ( PRDM16/ABL1 ratio ≥ 0.010). High PRDM16 expression significantly correlated with DNMT3A (43% vs. 15%, P  〈 0.001) and NPM1 (43% vs. 21%, P = 0.010) mutations and partial tandem duplication of KMT2A (22% vs. 1%, P  〈 0.001). Remarkably, high- PRDM16 -expression patients were frequent in the non-complete remission group (48% vs. 21%, P = 0.002). Overall survival (OS) was significantly worse in high- PRDM16 -expression patients than in low- PRDM16 -expression patients (5-year OS, 18% vs. 34%; P = 0.002). This trend was observed more clearly among patients aged 〈65 years (5-year OS, 21% vs. 50%; P = 0.001), particularly in FLT3 -ITD-negative patients in the intermediate cytogenetic risk group (5-year OS, 25% vs. 59%; P = 0.009). These results suggest that high PRDM16 expression is a significant predictive marker for poor prognosis in adult AML patients, similar to pediatric AML patients. This article is protected by copyright. All rights reserved.
    Print ISSN: 1045-2257
    Electronic ISSN: 1098-2264
    Topics: Biology , Medicine
    Published by Wiley-Blackwell
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  • 3
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    Novel neuroprotective action of prothymosin alpha-derived peptide against retinal and brain ischemic damages (2012)
    Wiley-Blackwell
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    Publication Date: 2012-12-20
    Description: Prothymosin alpha (ProTα), a nuclear protein, is implicated in the inhibition of ischemia-induced necrosis as well as apoptosis in the brain and retina. Although ProTα has multiple biological functions through distinct regions in its sequence, it has remained which region is involved in this neuroprotection. The present study reported that the active core peptide sequence P 30 (amino acids 49–78) of ProTα exerts its full survival effect in cultured cortical neurons against ischemic stress. Our in vivo study revealed that intravitreous administration of P 30 at 24 h after retinal ischemia significantly blocks the ischemia-induced functional damages of retina at day 7. In addition, P 30 completely rescued the retinal ischemia-induced ganglion cell damages at day 7 after the ischemic stress, along with partial blockade of the loss of bipolar, amacrine and photoreceptor cells. On the other hand, intracerebroventricular (3 nmol) or systemic (1 mg/kg; i.v.) injection of P 30 at 1 h after cerebral ischemia (1 h tMCAO) significantly blocked the ischemia-induced brain damages and disruption of blood vessels. Systemic P 30 delivery (1 mg/kg; i.v.) also significantly ameliorated the ischemic brain caused by photochemically induced thrombosis. Taken together, this study confers a precise demonstration about the novel protective activity of ProTα-derived small peptide P 30 against the ischemic damages in vitro and in vivo . © 2012 International Society for Neurochemistry, J. Neurochem. (2012) 10.1111/jnc.12132
    Print ISSN: 0022-3042
    Electronic ISSN: 1471-4159
    Topics: Medicine
    Published by Wiley-Blackwell on behalf of The International Society for Neurochemistry.
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  • 4
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    Management of breast papillary lesions diagnosed at ultrasound-guided vacuum-assisted and core needle biopsies (2014)
    Wiley-Blackwell
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    Publication Date: 2014-07-06
    Description: Aim To assess the diagnostic accuracy and outcome of breast papillary lesions diagnosed by ultrasound-guided core needle biopsy (CB) or vacuum-assisted “mammotome” biopsy (MT), and whether no surgical excision is justified in non-malignant papillary lesions so diagnosed. Methods and Results Among totally 3219 (MT2195/CB1024, respectively) breast biopsies spanning 5 years, 185 (5.7%) papillary lesions [MT162(88%)/CB23(12%)] were identified. Of these, (i) 142 cases (77%. MT/CB:125/17) were benign, 24 (13%. 23/1) were atypical and 19 (10%. 14/5) were malignant. (ii) Of the 142 benign cases, 114 had imaging follow-up (FU) [FU period 2-81 months] and 17/114 cases were excised and four were malignant (3.5%) [FU period 4-57 months]. Of the 24 atypical cases (23 had FU), 19 were excised [benign in 6 (32%) and malignant in 13 (68%)]. The remaining four cases were considered non-malignant [FU period 7-54 months]. Conclusions Benign papillary lesions diagnosed by MT or CB might not require immediate excision, but should receive imaging FU for at least five years. Excision should be performed in cases showing changes in imaging features as the possibilities of carcinoma co-existing with papilloma or carcinoma developing from papilloma cannot be excluded, as illustrated by the 4% upgrade rate at excision in this study. This article is protected by copyright. All rights reserved.
    Print ISSN: 0309-0167
    Electronic ISSN: 1365-2559
    Topics: Medicine
    Published by Wiley-Blackwell
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  • 5
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    Structural reorganization of the bacterial cell-division protein FtsZ from Staphylococcus aureus (2012)
    Wiley-Blackwell
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    Publication Date: 2012-09-06
    Description: FtsZ is a key molecule in bacterial cell division. In the presence of GTP, it polymerizes into tubulin-like protofilaments by head-to-tail association. Protofilaments of FtsZ seem to adopt a straight or a curved conformation in relation to the bound nucleotide. However, although several bacterial and archaeal FtsZ structures have been determined, all of the structures reported previously are considered to have a curved conformation. In this study, structures of FtsZ from Staphylococcus aureus ( Sa FtsZ) were determined in apo, GDP-bound and inhibitor-complex forms and it was found that Sa FtsZ undergoes marked conformational changes. The accumulated evidence suggests that the GDP-bound structure has the features of the straight form. The structural change between the curved and straight forms shows intriguing similarity to the eukaryotic cytoskeletal protein tubulin. Furthermore, the structure of the apo form showed an unexpectedly large conformational change in the core region. FtsZ has also been recognized as a novel target for antibacterial drugs. The structure of the complex with the inhibitor PC190723, which has potent and selective antistaphylococcal activity, indicated that the inhibitor binds at the cleft between the two subdomains.
    Print ISSN: 0907-4449
    Electronic ISSN: 1399-0047
    Topics: Chemistry and Pharmacology , Geosciences , Physics
    Published by Wiley-Blackwell on behalf of International Union of Crystallography (IUCr).
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