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- Kang, E. Y., et al.
(author)
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CCNE1 and survival of patients with tubo-ovarian high-grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study
- 2023
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In: Cancer. - : Wiley. - 0008-543X .- 1097-0142. ; 129:5, s. 697-713
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Journal article (peer-reviewed)abstract
- Background: Cyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo-ovarian high-grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1 amplification and CCNE1 overexpression with survival, but to date no large-scale, histotype-specific validation has been performed. The hypothesis was that high-level amplification of CCNE1 and CCNE1 overexpression, as well as a combination of the two, are linked to shorter overall survival in HGSC. Methods: Within the Ovarian Tumor Tissue Analysis consortium, amplification status and protein level in 3029 HGSC cases and mRNA expression in 2419 samples were investigated. Results: High-level amplification (>8 copies by chromogenic in situ hybridization) was found in 8.6% of HGSC and overexpression (>60% with at least 5% demonstrating strong intensity by immunohistochemistry) was found in 22.4%. CCNE1 high-level amplification and overexpression both were linked to shorter overall survival in multivariate survival analysis adjusted for age and stage, with hazard stratification by study (hazard ratio [HR], 1.26; 95% CI, 1.08-1.47, p = .034, and HR, 1.18; 95% CI, 1.05-1.32, p = .015, respectively). This was also true for cases with combined high-level amplification/overexpression (HR, 1.26; 95% CI, 1.09-1.47, p = .033). CCNE1 mRNA expression was not associated with overall survival (HR, 1.00 per 1-SD increase; 95% CI, 0.94-1.06; p = .58). CCNE1 high-level amplification is mutually exclusive with the presence of germline BRCA1/2 pathogenic variants and shows an inverse association to RB1 loss. Conclusion: This study provides large-scale validation that CCNE1 high-level amplification is associated with shorter survival, supporting its utility as a prognostic biomarker in HGSC.
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- Ortigoza-Escobar, Juan Darío, et al.
(author)
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Free-thiamine is a potential biomarker of thiamine transporter-2 deficiency: a treatable cause of Leigh syndrome.
- 2016
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In: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156. ; 139:Pt 1, s. 31-8
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Journal article (peer-reviewed)abstract
- Thiamine transporter-2 deficiency is caused by mutations in the SLC19A3 gene. As opposed to other causes of Leigh syndrome, early administration of thiamine and biotin has a dramatic and immediate clinical effect. New biochemical markers are needed to aid in early diagnosis and timely therapeutic intervention. Thiamine derivatives were analysed by high performance liquid chromatography in 106 whole blood and 38 cerebrospinal fluid samples from paediatric controls, 16 cerebrospinal fluid samples from patients with Leigh syndrome, six of whom harboured mutations in the SLC19A3 gene, and 49 patients with other neurological disorders. Free-thiamine was remarkably reduced in the cerebrospinal fluid of five SLC19A3 patients before treatment. In contrast, free-thiamine was slightly decreased in 15.2% of patients with other neurological conditions, and above the reference range in one SLC19A3 patient on thiamine supplementation. We also observed a severe deficiency of free-thiamine and low levels of thiamine diphosphate in fibroblasts from SLC19A3 patients. Surprisingly, pyruvate dehydrogenase activity and mitochondrial substrate oxidation rates were within the control range. Thiamine derivatives normalized after the addition of thiamine to the culture medium. In conclusion, we found a profound deficiency of free-thiamine in the CSF and fibroblasts of patients with thiamine transporter-2 deficiency. Thiamine supplementation led to clinical improvement in patients early treated and restored thiamine values in fibroblasts and cerebrospinal fluid.
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- Chavez-Caiza, J., et al.
(author)
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Unveiling the effect of sacrificial agent amount in the CO2 photoreduction performed in a flow reactor
- 2024
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In: Journal of CO2 Utilization. - : Elsevier BV. - 2212-9820 .- 2212-9839. ; 83
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Journal article (peer-reviewed)abstract
- The use of sacrificial agents in photocatalysis is a powerful resource to enhance the performance of photoactive materials. Despite its importance, the effect of the amount of sacrificial agent is not properly described in the literature. In this paper, we have focused on the role of EtOH in the photoreduction of CO2 to CH4 using Cu-P25 photocatalysts in a flow reactor. We found that the production of CH4 increased with the concentration of EtOH, achieving an outstanding CH4 production yield of 235 mu mol/(g & sdot;h) for a flow of 0.25 mu mol/min of EtOH in the gas stream, hinting at the important role of the sacrificial agent in the reaction. The catalytic results together with the characterization of the materials highlight the need to achieve a minimum surface coverage of EtOH on the surface of the catalyst to control the reaction pathway. The adsorption of EtOH is a key factor in boosting the catalytic activity of the best-performing catalyst and producing CH4 from CO2 photoreduction and C2H4O from the photooxidation of EtOH, obtaining two easily separable interesting products for industrial applications in one reaction.
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