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  • 1
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 0730-2312
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: To confirm the results of a previous report on the use of monoclonal antibodies in immunocytochemical assays of sputums for the early detection of lung cancer, we designed a new prospective trial in an independent clinical trial population. Since well-characterized Stage I resected non-small cell lung cancer patients have a low rate of tumor relapse and a high (1-3%/year) chance of developing a second primary lung cancer, they comprise a very favorable group for conducting an early lung cancer detection trial. The rate of new lung cancer is about 10-fold in excess of a standard “high” risk population of smokers.To optimize the chance for a favorable outcome, all of the technical components for the trial have been systematically evaluated to ensure that optimal procedures are employed. For example, automated immunostaining of the sputum specimens will be performed.Bronchial lavages will be analyzed in a subset of the trial participants to define additional targets for early lung cancer detection. Two markers will be quantitated, including gastrin releasing peptide and peptidyl glycine α-amidating monooxygenase activity. These two markers assess the epithelium's capacity to produce growth factors which may be central to the biology of tumor promotion. Since these assays have not been performed in this context before, we attempted to optimize the specimen handling to permit the receipt of the material from a range of collaborating clinical sites in a condition that permits accurate quantitation of these two biomarkers.Efforts to standardize the assay endpoint stimulated the development of computer-assisted methods of immunocytochemical analysis. An algorithm for image analysis was developed as a result of systematic analysis of a range of potentially quantifiable assay endpoints with a panel of teaching cases. When a sampling of the original immunostained material from the first monoclonal antibody-based early lung cancer detection report was reanalyzed using the image analysis algorithm, a 90% concurrence with the original immunostaining interpretation was observed. These results suggest that there was an objective basis to the first report and that image analysis can greatly refine the process of early lung cancer detection research.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 0730-2312
    Keywords: carcinogenesis ; chemoprevention ; intermediate end point ; biomarkers ; differentiation ; growth factors ; lung cancer ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: The need for validate intermediate end point markers to facilitate lung cancer chemointervention research is competing. Three major classes of lung markers are relevant for this application. Since lung cancer includes four distinct hitologies, markers that map degrees of histologic differentiation are important. Many of the markers for squamous differentiation overlap with the candidates for application in the study of head and neck cancer. Production of tissue-specific cell product especially for surfactant or CEA is of interest, because the gene structure is known and many differentiation-related polymorphisms exist. This strategy would be useful for adenomatous type of tissue. A second type of marker is the broad group of differentiation markers. The carbohydrates or blood group-like antigens comprise a representative example. Carbohydrate structures are expressed in a specific sequence during fetal processes, and this sequence appears to reverse with the development of a cancer. Retrodifferentiation of specific differentiation markers is the basis of a major effort to effect earlier lung cancer detection using sputum immunocytochemistry. The final class includes markers which affects either positive or negative aspects of growths. Candidates in this area include growth factors or their receptors or genes that regulate growth. If the intermediate end point marker reflects tumor biology and is in that casual path of tumor progression, serial observation of that parameter should indicate the success of the intervention. In all three of these examples the clinical material to be analyzed could be sputum specimens bonrchial biopsies or resected lung tissue. Systematic analysis of these markers in context of intervention trials required to validate their utility. Long term clinical follow up will demonstrate the degree of concordance between biomarkers and more traditional clinical trial end points and will establish if such tools can play a role in catalyzing the rate of prevention research. © 1992 Wiley-Liss, Inc.
    Additional Material: 1 Tab.
    Type of Medium: Electronic Resource
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