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61.
Astuti D Douglas F Lennard TW Aligianis IA Woodward ER Evans DG Eng C Latif F Maher ER 《Lancet》2001,357(9263):1181-1182
The genetic basis for familial phaeochromocytoma is unknown in many cases. Since the disorder has been reported in some cases of familial head and neck paraganglioma, which is caused by a mutation in the gene encoding succinate dehydrogenase complex subunit D (SDHD), we investigated this gene in kindreds with familial phaeochromocytoma. A germline SDHD frameshift mutation was identified in a two-generation family consisting of four children with phaeochromocytoma, but somatic mutations were not detected in 24 sporadic phaeochromocytoma tumours. Germline SDHD mutation analysis should be done in individuals with familial, multiple, or early-onset phaeochromocytomas even if a personal or family history of head and neck paraganglioma is absent. 相似文献
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Astuti D Morris M Krona C Abel F Gentle D Martinsson T Kogner P Neumann HP Voutilainen R Eng C Rustin P Latif F Maher ER 《British journal of cancer》2004,91(10):1835-1841
Germline mutations in the succinate dehydrogenase (SDH) (mitochondrial respiratory chain complex II) subunit B gene, SDHB, cause susceptibility to head and neck paraganglioma and phaeochromocytoma. Previously, we did not identify somatic SDHB mutations in sporadic phaeochromocytoma, but SDHB maps to 1p36, a region of frequent loss of heterozygosity (LOH) in neuroblastoma as well. Hence, to evaluate SDHB as a candidate neuroblastoma tumour suppressor gene (TSG) we performed mutation analysis in 46 primary neuroblastomas by direct sequencing, but did not identify germline or somatic SDHB mutations. As TSGs such as RASSF1A are frequently inactivated by promoter region hypermethylation, we designed a methylation-sensitive PCR-based assay to detect SDHB promoter region methylation. In 21% of primary neuroblastomas and 32% of phaeochromocytomas (32%) methylated (and unmethylated) alleles were detected. Although promoter region methylation was also detected in two neuroblastoma cell lines, this was not associated with silencing of SDHB expression, and treatment with a demethylating agent (5-azacytidine) did not increase SDH activity. These findings suggest that although germline SDHB mutations are an important cause of phaeochromocytoma susceptibility, somatic inactivation of SDHB does not have a major role in sporadic neural crest tumours and SDHB is not the target of 1p36 allele loss in neuroblastoma and phaeochromocytoma. 相似文献
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Ruth A Jonathan Karien I E M Wijffels Wenny Peeters Peter C M de Wilde Henri A M Marres Matthias A W Merkx Egbert Oosterwijk Albert J van der Kogel Johannes H A M Kaanders 《Radiotherapy and oncology》2006,79(3):288-297
BACKGROUND AND PURPOSE: Hypoxic radioresistance is an important cause for treatment failure in a number of tumor types including head and neck cancers. Recent studies suggest that outcome can be improved by oxygenation modifying treatments such as ARCON. A robust endogenous marker of hypoxia might be a valuable aid to select patients for such treatments. The aim of this investigation was to study associations between the putative endogenous hypoxia markers CA-IX, Glut-1 and Glut-3 and clinical tumor and patient characteristics and to evaluate the prognostic value of these markers. PATIENTS AND METHODS: Tumor biopsies from 58 patients treated with ARCON in a phase II trial were included. Tumor sections were immunohistochemically stained for CA-IX, Glut-1 and Glut-3. Sections were scored for relative tumor area stained by the markers (CA-IX and Glut-3) and for intensity of staining (Glut-1 and Glut-3). Further, sections were stained for CD34, an endothelial marker to assess microvascular density. RESULTS: Staining of CA-IX and Glut-3 was observed at some distance from vessels and adjacent to necrosis. Glut-1 staining was generally very diffuse. The distribution of clinical characteristics was equal between tumors with high and low marker expression. Significant differences were found for locoregional control (P = 0.04) and for freedom of distant metastases (P = 0.02) in favour of patients with high CA-IX positivity (>25% of tumor area). High Glut-3 expression was associated with a better locoregional control (P = 0.04). Higher Glut-1 intensity was associated with an increased rate of distant metastases (P = 0.0005) and a worse overall survival (P = 0.001). CONCLUSIONS: The inconsistent associations with outcome of CA-IX and the glucose transporters indicate that different factors play a role in up-regulation of these markers. Compared to studies with conventional treatment, the correlation between CA-IX expression and Glut-3 expression and outcome was reversed after treatment with ARCON. This does not support the potential of any of these proteins as very specific and robust hypoxia markers. 相似文献
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Circulating Prostate‐Specific Antigen and Telomere Length in a Nationally Representative Sample of Men Without History of Prostate Cancer
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Rodiansono Heny Puspita Dewi Kamilia Mustikasari Maria Dewi Astuti Sadang Husain Sutomo 《RSC advances》2022,12(21):13319
Molybdenum oxide-modified ruthenium on titanium oxide (Ru–(y)MoOx/TiO2; y is the loading amount of Mo) catalysts show high activity for the hydroconversion of carboxylic acids to the corresponding alcohols (fatty alcohols) and aliphatic alkanes (biofuels) in 2-propanol/water (4.0/1.0 v/v) solvent in a batch reactor under mild reaction conditions. Among the Ru–(y)MoOx/TiO2 catalysts tested, the Ru–(0.026)MoOx/TiO2 (Mo loading amount of 0.026 mmol g−1) catalyst shows the highest yield of aliphatic n-alkanes from hydroconversion of coconut oil derived lauric acid and various aliphatic fatty acid C6–C18 precursors at 170–230 °C, 30–40 bar for 7–20 h. Over Ru–(0.026)MoOx/TiO2, as the best catalyst, the hydroconversion of lauric acid at lower reaction temperatures (130 ≥ T ≤ 150 °C) produced dodecane-1-ol and dodecyl dodecanoate as the result of further esterification of lauric acid and the corresponding alcohols. An increase in reaction temperature up to 230 °C significantly enhanced the degree of hydrodeoxygenation of lauric acid and produced n-dodecane with maximum yield (up to 80%) at 230 °C, H2 40 bar for 7 h. Notably, the reusability of the Ru–(0.026)MoOx/TiO2 catalyst is slightly limited by the aggregation of Ru nanoparticles and the collapse of the catalyst structure.Ru–(y)MoOx/TiO2 catalysed the hydroconversion of lauric acid to allow a remarkable yield of n-dodecane (up to 80%) under mild reaction conditions. 相似文献