40 research outputs found

    Overexpression of metastasis-associated MTA1 mRNA in invasive oesophageal carcinomas

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    The MTA1 gene is a recently identified novel candidate breast cancer metastasis-associated gene which has been implicated in the signal transduction or regulation of gene expression. We examined the mRNA expression levels of the MTA1, the human homologue of the rat mta1 gene in 47 surgically resected oesophageal squamous cell carcinomas by quantitative reverse transcription polymerase chain reaction. The relative overexpression of MTA1 mRNA (tumour/normal ratio ≥ 2) was observed in 16 out of 47 (34.0%) oesophageal carcinomas. Oesophageal tumours overexpressing MTA1 mRNA (T/N ratio ≥ 2) showed significantly higher frequencies of adventitial invasion (P < 0.05) and lymph node metastasis (P < 0.05), and tended to have a higher rate of lymphatic involvement than the remaining tumours. Thus, the data suggest that the MTA1 gene might play an important role in invasion and metastasis of oesophageal carcinomas. © 1999 Cancer Research Campaig

    Comprehensive microRNA profiling in acetaminophen toxicity identifies novel circulating biomarkers for human liver and kidney injury

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    Our objective was to identify microRNA (miRNA) biomarkers of drug-induced liver and kidney injury by profiling the circulating miRNome in patients with acetaminophen overdose. Plasma miRNAs were quantified in age- and sex-matched overdose patients with (N=27) and without (N=27) organ injury (APAP-TOX and APAP-no TOX, respectively). Classifier miRNAs were tested in a separate cohort (N=81). miRNA specificity was determined in non-acetaminophen liver injury and murine models. Sensitivity was tested by stratification of patients at hospital presentation (N=67). From 1809 miRNAs, 75 were 3-fold or more increased and 46 were 3-fold or more decreased with APAP-TOX. A 16 miRNA classifier model accurately diagnosed APAP-TOX in the test cohort. In humans, the miRNAs with the largest increase (miR-122-5p, miR-885-5p, miR-151a-3p) and the highest rank in the classifier model (miR-382-5p) accurately reported non-acetaminophen liver injury and were unaffected by kidney injury. miR-122-5p was more sensitive than ALT for reporting liver injury at hospital presentation, especially combined with miR-483-3p. A miRNA panel was associated with human kidney dysfunction. In mice, miR-122-5p, miR-151a-3p and miR-382-5p specifically reported APAP toxicity - being unaffected by drug-induced kidney injury. Profiling of acetaminophen toxicity identified multiple miRNAs that report acute liver injury and potential biomarkers of drug-induced kidney injury

    The 10-item kessler psychological distress measure (K10) as a screening instrument in older individuals

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    OBJECTIVE: To provide population-based Kessler Psychological Distress scale (K10) normative data for older adults and cut scores for screening. PARTICIPANTS: Adults age ≥ 65 years who participated in either the 1997 or 2007 Australian National Surveys of Mental Health and Well-being (N = 3,697). MEASUREMENTS: The proportion of respondents who reported psychological distress, and the correspondence of K10 scores with diagnosis of mental disorder, disability, and service use. RESULTS: Scores on the K10 corresponded well with rates of mental disorder. Higher K10 scores were associated with increased levels of internalizing disorder, comorbidity, functional disability, and service use. Receiver operating characteristic curve analysis revealed an area under the curve score of 0.86, suggesting good predictive power. For screening purposes, a cut score of 15 was found to be associated with the best balance between sensitivity (0.77) and specificity (0.78). Similar levels of predictive power were observed across various subgroups of the population. Score ranges for groups who met criteria for a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition affective or anxiety disorder showed that for those age 65-75, a score of 20 or greater and a score of 17 or greater for those older than 75 years warrant heightened clinical interest. CONCLUSIONS: The K10 exhibits sensitivity to internalizing disorders as they occur across the lifespan and can be used with confidence when assessing psychological distress in old-age community dwellers. The significant association between higher K10 scores and disability suggests that the presence of psychological distress, regardless of diagnostic status, requires clinician attention
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