2 research outputs found
A Portuguese patient homozygous for the -25G>A mutation of the HAMP promoter shows evidence of steady-state transcription but fails to up-regulate hepcidin levels by iron.
Blood. 2005 Oct 15;106(8):2922-3.
A Portuguese patient homozygous for the -25G>A mutation of the HAMP promoter shows evidence of steady-state transcription but fails to up-regulate hepcidin levels by iron.
Porto G, Roetto A, Daraio F, Pinto JP, Almeida S, Bacelar C, Nemeth E, Ganz T, Camaschella C.
PMID: 16204153 [PubMed - indexed for MEDLINE]Free Article
Publication Types, MeSH Terms, SubstancesPublication Types:
Letter
Research Support, Non-U.S. Gov't
MeSH Terms:
Antimicrobial Cationic Peptides/genetics*
Antimicrobial Cationic Peptides/urine
Glycine/genetics*
Hemochromatosis/genetics
Homozygote*
Humans
Iron/pharmacology*
Mutation/genetics
Portugal
Promoter Regions, Genetic/genetics*
Transcription, Genetic/genetics*
Up-Regulation/drug effects*
Substances:
Antimicrobial Cationic Peptides
hepcidin
Glycine
Iron
LinkOut - more resourcesFull Text Sources:
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Other Literature Sources:
COS Scholar Universe
Medical:
Genetics Home Reference - HAMP Gene - Genetics Home Reference
Molecular Biology Databases:
IRON - HSDB
GLYCINE - HSD
Prognostic value of test(s) for O6-methylguanineâDNA methyltransferase (MGMT) promoter methylation for predicting overall survival in people with glioblastoma treated with temozolomide
BACKGROUND: Glioblastoma is an aggressive form of brain cancer. Approximately five in 100 people with glioblastoma survive for five years past diagnosis. Glioblastomas that have a particular modification to their DNA (called methylation) in a particular region (the O(6)âmethylguanineâDNA methyltransferase (MGMT) promoter) respond better to treatment with chemotherapy using a drug called temozolomide. OBJECTIVES: To determine which method for assessing MGMT methylation status best predicts overall survival in people diagnosed with glioblastoma who are treated with temozolomide. SEARCH METHODS: We searched MEDLINE, Embase, BIOSIS, Web of Science Conference Proceedings Citation Index to December 2018, and examined reference lists. For economic evaluation studies, we additionally searched NHS Economic Evaluation Database (EED) up to December 2014. SELECTION CRITERIA: Eligible studies were longitudinal (cohort) studies of adults with diagnosed glioblastoma treated with temozolomide with/without radiotherapy/surgery. Studies had to have related MGMT status in tumour tissue (assessed by one or more method) with overall survival and presented results as hazard ratios or with sufficient information (e.g. KaplanâMeier curves) for us to estimate hazard ratios. We focused mainly on studies comparing two or more methods, and listed brief details of articles that examined a single method of measuring MGMT promoter methylation. We also sought economic evaluations conducted alongside trials, modelling studies and cost analysis. DATA COLLECTION AND ANALYSIS: Two review authors independently undertook all steps of the identification and data extraction process for multipleâmethod studies. We assessed risk of bias and applicability using our own modified and extended version of the QUality In Prognosis Studies (QUIPS) tool. We compared different techniques, exact promoter regions (5'âcytosineâphosphateâguanineâ3' (CpG) sites) and thresholds for interpretation within studies by examining hazard ratios. We performed metaâanalyses for comparisons of the three most commonly examined methods (immunohistochemistry (IHC), methylationâspecific polymerase chain reaction (MSP) and pyrosequencing (PSQ)), with ratios of hazard ratios (RHR), using an imputed value of the correlation between results based on the same individuals. MAIN RESULTS: We included 32 independent cohorts involving 3474 people that compared two or more methods. We found evidence that MSP (CpG sites 76 to 80 and 84 to 87) is more prognostic than IHC for MGMT protein at varying thresholds (RHR 1.31, 95% confidence interval (CI) 1.01 to 1.71). We also found evidence that PSQ is more prognostic than IHC for MGMT protein at various thresholds (RHR 1.36, 95% CI 1.01 to 1.84). The data suggest that PSQ (mainly at CpG sites 74 to 78, using various thresholds) is slightly more prognostic than MSP at sites 76 to 80 and 84 to 87 (RHR 1.14, 95% CI 0.87 to 1.48). Many variants of PSQ have been compared, although we did not see any strong and consistent messages from the results. Targeting multiple CpG sites is likely to be more prognostic than targeting just one. In addition, we identified and summarised 190 articles describing a single method for measuring MGMT promoter methylation status. AUTHORS' CONCLUSIONS: PSQ and MSP appear more prognostic for overall survival than IHC. Strong evidence is not available to draw conclusions with confidence about the best CpG sites or thresholds for quantitative methods. MSP has been studied mainly for CpG sites 76 to 80 and 84 to 87 and PSQ at CpG sites ranging from 72 to 95. A threshold of 9% for CpG sites 74 to 78 performed better than higher thresholds of 28% or 29% in two of three goodâquality studies making such comparisons