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At least 235 records · Page 13Linked to original sources
PubMed1999

Diffuse bony metastasis from transitional cell carcinoma of urinary bladder: a case report and review of literature.

The incidence and mortality rate of bladder carcinoma remains high and is in fact increasing despite the application of new treatment strategies. Transitional cell carcinoma (TCC) is the most common carcinoma of the bladder (> 90% of cases). We report a case of a 60 year-old man with multiple bony metastases of TCC affecting the humerus, femur, spine, iliac wing, and ribs. The metastases were discovered within a year after first presentation of hematuria with a subsequent biopsy diagnosis of TCC of bladder, Grade 3 of 3 with no definite muscle invasion. Metastasis of TCC of bladder to bone is an uncommon occurrence when compared with breast and prostate carcinoma. This may be due to intrinsic properties of tumor cells and/or mechanisms of metastases. Recent studies confirm that bone is the preferred site of metastasis (35%) of TCC outside of the pelvis, with the spine being the most common site (40% of bony metastases). Histologic grading, emphasizing the presence of invasion, is generally accepted as being very important prognostically. The importance of diagnostic screening tests including urothelial biomarkers profile in reducing the mortality rate from first onset of hematuria is discussed such as tumor-associated antigen M344 and DD23.

Biopsy, Needle↗
PubMed2005

From single cell gene-based diagnostics to diagnostic genomics: current applications and future perspectives.

Molecular diagnostics is a branch of clinical diagnostics that uses primarily DNA or RNA as a biomarker for clinical testing. It combines various gene-based amplification technologies with highly sophisticated detection methods for the clinical diagnosis of a vast variety of diseases including infectious diseases, cancer, and inherited diseases. The principal application of gene-based amplification technology is to identify pathogen or gene-specific nucleic acid sequences that are used as surrogate markers for the identification of either infectious pathogens or alteration of disease-related genes. There are generally three classes of gene-based amplification technologies: target-based, e.g., PCR; probe-based, e.g., LCR; and signal-based, e.g., bDNA. Real-time detection of PCR allows us to quantify amplified amplicons with a broad dynamic range and it offers a unique way to detect genetic mutations. Other technologies such as immuno-PCR and bio-barcode assay (BCA) combine different amplification tactics offering extreme detection sensitivity ranging from femtogram (10(-15)) to zeptogram (10(-21)). Even though quantum dots technology is in its infant stage, its potential to further increase diagnostic sensitivity and specificity is likely beyond our current imagination. Future diagnostic technologies include the use of genomic and proteomic approaches especially in pure cell types or even in the single-cell level, which open up endless new possibilities for gene-based diagnostics at entirely different levels. In this article, principles of various current gene-based amplification and detection technologies along with their clinical applications are discussed. New technologies that could potentially be used in future gene-based diagnosis are introduced.

Genetics, Medical↗
PubMed1997

Contemporary non-imaging methods in diagnosis of bladder cancer: a review.

The early diagnosis of bladder cancer is central to the effective treatment of the disease. Presently, the detection of bladder tumors relies on cystoscopy and there are no methods available to easily and specifically identify the presence of bladder cancer cells. A variety of new technologies and potential tumor markers are being studied in bladder cancer and some are being translated into clinical use. It is important to realise that all available results on the diagnostic value of tumor markers do not allow firm clinical recommendations, but tests based on biomarkers will undoubtedly influence the management of bladder cancer in the near future.

Antigens, Neoplasm↗
PubMed1997

Differences in the urinary metabolites of the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in black and white smokers.

Incidence and mortality rates for lung cancer in the United States are significantly greater in blacks than in whites. This disparity cannot be explained by differences in smoking behavior. We hypothesize that the observed racial differences in risk may be due to differences in the metabolic activation or detoxification of the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). To test this, different biomarkers of NNK exposure and metabolism, including the urinary metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and the presumed detoxification product [4-(methylnitrosamino)-1-(3-pyridyl)but-1-yl]-beta-O-D-glucosiduronic acid (NNAL-Gluc), were examined along with questionnaire data on lifestyle habits and diet in a metabolic epidemiological study of 34 black and 27 white healthy smokers. Results demonstrated that urinary NNAL-Gluc:NNAL ratios, a likely indicator of NNAL glucuronidation and detoxification, were significantly greater in whites than in blacks (P < 0.02). In addition, two phenotypes were apparent by probit analysis representing poor (ratio < 6) and extensive (ratio > or = 6) glucuronidation groups. The proportion of blacks falling into the former, potentially high-risk group was significantly greater than that of whites (P < 0.05). The absolute levels of urinary NNAL, NNAL-Gluc, and cotinine were also greater in blacks than in whites when adjusted for the number of cigarettes smoked. None of the observed racial differences could be explained by dissimilarities in exposure or other sociodemographic or dietary factors. Also, it is unlikely that the dissimilarities are due to racial differences in preference for mentholated cigarettes, because chronic administration of menthol to NNK-treated rats did not result in either increases in urinary total NNAL or decreases in NNAL-Gluc:NNAL ratios. Altogether, these results suggest that racial differences in NNAL glucuronidation, a putative detoxification pathway for NNK, may explain in part the observed differences in cancer risk.

Adult↗
PubMed2006

Large-scale human metabolomics studies: a strategy for data (pre-) processing and validation.

A large metabolomics study was performed on 600 plasma samples taken at four time points before and after a single intake of a high fat test meal by obese and lean subjects. All samples were analyzed by a liquid chromatography-mass spectrometry (LC-MS) lipidomic method for metabolic profiling. A pragmatic approach combining several well-established statistical methods was developed for processing this large data set in order to detect small differences in metabolic profiles in combination with a large biological variation. Such metabolomics studies require a careful analytical and statistical protocol. The strategy included data preprocessing, data analysis, and validation of statistical models. After several data preprocessing steps, partial least-squares discriminant analysis (PLS-DA) was used for finding biomarkers. To validate the found biomarkers statistically, the PLS-DA models were validated by means of a permutation test, biomarker models, and noninformative models. Univariate plots of potential biomarkers were used to obtain insight in up- or downregulation. The strategy proposed proved to be applicable for dealing with large-scale human metabolomics studies.

Chromatography, Liquid↗
PubMedDate not supplied

Use of a complex approach for assessment of metamizole sodium and acetylsalicylic acid toxicity, genotoxicity and cytotoxicity.

A complex approach based on the use of test organisms belonging to different systematic groups (plants, invertebrates and vertebrates), as well as the nucleolar biomarker and the micronucleus test on their cells, was applied to assess the toxicity, cytotoxicity and genotoxicity of two pharmaceutical substances (metamizole sodium and acetylsalicylic acid) applied at ic(50) concentrations for mammalian cells. The compound acetylsalicylic acid was evaluated at a concentration (1.6 x 10(3) mg l(-1)) that was non-toxic for bioassays based on fish (Carassius auratus gibelio) and hydra (Hydra attenuata) and acutely toxic for bioassays with ceriodaphnia (Ceriodaphnia affinis) and onion (Allium cepa). The metamizole sodium solution (6.25%) demonstrated acute toxicity for the whole set of test organisms. Both drugs, after their 30-360 min influence on the test organisms, first changed the nucleolar size in plant and animal cells (i.e. the transcriptional activity of ribosomal genes was affected most significantly). Moreover, the metamizole sodium solution caused nucleolar structural damage in 90% of hydra cells as early as after 30 min of exposure. The acetylsalicylic acid solution inhibited essentially the rate of cell division in the meristem of onion roots (the mitotic index decreased to 9.6 per thousand, as compared 51.7 per thousand for the control). The carp incubation and the onion germination in the acetylsalicylic acid solution showed a reproducible increase in the frequency of cells with micronuclei (2 and 5.5 times, respectively) and double nuclei (3 and 1.5 times, respectively). The approach described herein may be applied for obtaining rapid, cost-efficient and useful supplementary data on different types of toxicity for marketed drugs as well as for drugs under development.

Allium↗
PubMed2026

Pulmonary fibrosis after COVID-19 is characterized by airway abnormalities and elevated club cell secretory protein-16.

BACKGROUNDThere are no known serum biomarkers that provide mechanistic insight or prognostic enrichment for post-COVID-19 pulmonary fibrosis.METHODSWe tested associations of serum biomarkers with radiographic fibrosis-like abnormalities (reticulation, traction bronchiectasis, or honeycombing) on thoracic computed tomography (CT) scans 4 months, 15 months, and 3 years after hospitalization in an American discovery cohort of severe-to-critical COVID-19 survivors, and externally validated findings in 2 Canadian cohorts of moderate-to-critical COVID-19 survivors. In the discovery cohort, we investigated the dose-response relationship of the biomarker with CT-derived airway-to-lung ratio. We performed single-cell RNA sequencing (scRNA-seq) of transbronchial lung biopsies from COVID-19 survivors obtained 3 years after COVID-19 hospitalization and conducted immunofluorescence analysis of COVID-19 lung explants.RESULTSAmong 150 discovery cohort participants, only higher levels of circulating club cell secretory protein-16 (CC16, encoded by the SCGB1A1 gene) at hospital discharge, 4 months, 15 months, and 3 years were associated with thoracic CT fibrosis-like abnormalities in cross-sectional and longitudinal analyses. Higher CC16 levels were associated with thoracic CT fibrosis-like abnormalities in 2 validation cohorts (n = 56 and n = 37). CC16 levels were linearly associated with increased airway-to-lung ratio. scRNA-seq revealed increased proportions of epithelial cells expressing SCGB1A1 and SCGB1A1/MUC5B in COVID-19 survivors with fibrosis. Immunofluorescence analysis of COVID-19 lung explants demonstrated increased numbers of SCGB1A1-expressing epithelial cells only in small (<100 &#x3bc;m) airways, with 3-fold more CC16/MUC5B-coexpressing cells in respiratory bronchioles..CONCLUSION. Higher CC16 levels are associated with CT fibrosis-like abnormalities for up to 3 years following moderate-to-critical COVID-19. Increased CC16 reflects dysregulated small airway epithelial progenitor cell remodeling and increased expansion of CC16+MUC5B+ epithelial cells in respiratory bronchioles after COVID-19.TRIAL REGISTRATIONNot applicable.FUNDINGDepartment of Defense, NIH, and Japan Society for the Promotion of Science for Young Scientists.

Humans↗
PubMed2006

Bayesian detection of abnormal values in longitudinal biomarkers with an application to T/E ratio.

We developed a test that compares sequential measurements of a biomarker against previous readings performed on the same individual. A probability mass function expresses prior information on interindividual variations of intraindividual parameters. Then, the model progressively integrates new readings to more accurately quantify the characteristics of the individual. This Bayesian framework generalizes the two main approaches currently used in forensic toxicology for the detection of abnormal values of a biomarker. The specificity is independent of the number n of previous test results, with a model that gradually evolves from population-derived limits when n = 0 to individual-based cutoff thresholds when n is large. We applied this model to detect abnormal values in an athlete's steroid profile characterized by the testosterone over epitestosterone (T/E) marker. A cross-validation procedure was used for the estimation of prior densities as well as model validation. The heightened sensitivity/specificity relation obtained on a large data set shows that longitudinal monitoring of an athlete's steroid profile may be used efficiently to detect the abuse of testosterone and its precursors in sports. Mild assumptions make the model interesting for other areas of forensic toxicology.

Bayes Theorem↗
PubMed2005

Epidermal growth factor receptor, protein kinase B/Akt, and glioma response to erlotinib.

BACKGROUND: The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib (also known as Tarceva or OSI-774) has shown promising response rates in malignant gliomas. We investigated the association between expression of EGFR and downstream signaling components and the response of malignant gliomas to erlotinib in a phase I trial of erlotinib administered either alone or with the alkylating agent temozolomide. METHODS: Expression of EGFR and ligand-independent EGFRvIII mutant proteins and of phosphorylated protein kinase B (PKB)/Akt in specimens from glioma patients were assessed by immunohistochemistry. EGFR gene amplification was evaluated by fluorescence in situ hybridization. Mutations in PTEN and EGFR were assessed by polymerase chain reaction amplification and sequencing. Response was evaluated by sequential magnetic resonance imaging every 2 months. The Cochran-Mantel-Haenzel test was used to assess associations between biomarker status and response. All statistical tests were two-sided. RESULTS: Of 41 glioma patients, eight responded to treatment. Response to erlotinib was associated with EGFR expression (P = .07) and EGFR amplification (P = .08). These associations were stronger and statistically significant among the 29 patients initially diagnosed with glioblastoma multiforme (P = .03 and P = .02, respectively). Among six responders with sufficient tumor tissue, none had EGFRvIII mutations. None of the 22 tumors with high levels of phosphorylated PKB/Akt responded to erlotinib treatment, whereas eight of the 18 tumors with low levels of phosphorylated PKB/Akt responded to erlotinib treatment (P < .001). The level of phosphorylated PKB/Akt was also associated with time to progression (P < .001). CONCLUSIONS: Among glioma patients, those with glioblastoma multiforme tumors who have high levels of EGFR expression and low levels of phosphorylated PKB/Akt had better response to erlotinib treatment than those with low levels of EGFR expression and high levels of phosphorylated PKB/Akt.

Adult↗
PubMed2000

Preliminary evaluation of an in vitro test for assessment of excitotoxicity by measurement of early gene (c-fos mRNA) levels.

Using primary cultures of mouse cerebellar granule cells as an in vitro model system, it has been demonstrated that different profiles of temporal expression of the c-fos proto-oncogene are observed under non-excitotoxic and excitotoxic conditions. A ratio has been derived previously for the steady-state level of c-fos mRNA after 30 min and 240 min which suggests that a 240 min/30 min ratio of greater than 1 correlates with excitotoxicity, whereas a ratio of less than 1 correlates with a non-excitotoxic outcome. Moreover, a positive correlation is seen with abrogation of excitotoxicity in response to selective excitatory amino acid receptor antagonists. This test, proposed as a specific biomarker for excitotoxicity is undergoing prevalidation. Excitotoxicity is defined as neuronal cell death mediated by hyperactivation of glutamate receptor subtypes and therefore might be expected to be prevented by selective glutamate receptor antagonists. In preliminary evaluation studies, we have conducted work under the direction of the European Center for Validation of Alternate Methods (ECVAM) using compounds specified by ECVAM that have been subdivided into four groups based on known or presumed actions. These groups comprise: Group 1-endogenous/synthetic excitotoxins; Group 2-environmental, putative excitotoxins; Group 3-neurotoxic but non-excitotoxic compounds, and Group 4-non-toxic compounds. The results of this study support the proposal that the c-fos mRNA time-ratio test is a specific biomarker of excitotoxicity. Just as importantly, this test has the potential for application in screening newly-designed EAA receptor antagonists in the search for clinically relevant drugs to treat a variety of neuropathologies.

Animals↗
PubMed1994

Laboratory tests in rheumatology.

The most commonly used laboratory tests in the diagnosis and monitoring of rheumatic diseases are reviewed. Particular emphasis is placed on antinuclear antibodies as markers of specific rheumatic disorders and disease subsets. The use of synovial fluid tests to differentiate between inflammatory and noninflammatory rheumatic disorders is described as well as the use of common hematological tests.

Antibodies, Antinuclear↗