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  • 1
    Electronic Resource
    Electronic Resource
    Intermediate biomarkers in upper aerodigestive tract and lung chemoprevention trials (1992)
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 50 (1992), S. 33-38 
    Details
    ISSN: 0730-2312
    Keywords: chemoprevention ; field cancerization ; intermediate biomarker ; premalignant lesions ; upper aerodigestive tract cancer ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Chemoprevention trials in lung and upper aerodigestive tract (UADT) cancer are guided by the field cancerization hypothesis. Inhaled carcinogens place the entire epithelial lining at risk for the development of cancer. The hypothesis is supported by the occurrence of premalignant lesions, such as leukoplakia or squamous metaplasia, and multiple primary tumors within the field. The concept of carcinogenesis as a multistep process suggests the possibility of blocking or reversing the progression to invasive cancer with systemic treatment. A series of ongoing clinical trials will determine the efficacy of retinoid chemoprevention and will attempt to develop intermediate biomarkers. Biomarkers which reliably reflect progression towards cancer could be used to dramatically improve the efficiency of chemoprevention trials and also would aid in screening potential chemoprevention agents. Genomic biomarkers include non-specific estimates of ongoing DNA injury, such as micronuclei, as well as development of aneuploidy and alterations in oncogenes. A class of biomarkers of increasing importance assess proliferation and growth regulation, and include proliferating cell nuclear antigen (PCNA), TGF-β, EGFR and retinoid receptors. Other markers, such as the blood group antigens, reflect differentiation and may be associated with the development of premalignant lesions. Preliminary data from several of these markers has suggested and association with carcinogenic exposures and premalignant lesions, but none of these markers either alone or in panels have yet been validated as a reliable surrogate for the development of invasive cancer. © 1992 Wiley-Liss, Inc.
    Additional Material: 1 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcb.240501106
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  • 2
    Electronic Resource
    Electronic Resource
    Strategies for the application of biomarkers for risk assessment and efficacy in breast cancer chemoprevention trials (1993)
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 53 (1993), S. 37-43 
    Details
    ISSN: 0730-2312
    Keywords: Breast cancer ; chemoprevention ; genetic instability ; intermediate biomarkers ; multistep carcinogenesis ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Current chemoprevention trial designs based on epidemiological risk assessment and occurrence of cancer as an endpoint are inefficient and expensive. Novel biomarkers are needed to facilitate the development of chemopreventive interventions. The following four categories of biomarkers may be useful in prevention trials: histologic and morphometric markers; phenotypic markers of dysregulated proliferation, differentiation, and cell loss; specific oncogenes and growth regulators which are qualitatively or quantitatively altered in breast cancers; and markers of genetic and epigenetic instability. Some of these markers will be generally useful regardless of the chemopreventive approach used, whereas others may be uniquely useful in trials of specific chemopreventive agents [e.g., upregulation of progesterone receptor (PR) expression in response to tamoxifen]. The development of these markers requires three phases of study: “Phase I”: assessing the prevalence of the putative marker in malignant and premalignant tissue from individuals who have developed breast cancer; “Phase II”: assessing in vivo modulation of the biomarker by the proposed chemopreventive agent; and “Phase III”: applying the proposed biomarker in larger-scale trials of chemopreventive agent in high-risk populations, either before or after the development of a primary breast malignancy. The use of these biomarkers may also allow identification of novel targets for chemoprevention.
    Additional Material: 1 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcb.240531106
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  • 3
    Electronic Resource
    Electronic Resource
    Polyamine measurements in the uterine cervix (1997)
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 67 (1997), S. 125-132 
    Details
    ISSN: 0730-2312
    Keywords: chemoprevention ; cervical intraepithelial neoplasia (CIN) ; surrogate endpoint biomarker (SEB) ; α-difluoromethylornithine (DFMO) ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Cervical cancer remains a significant health problem. New strategies based on the molecular aspects of cervical carcinogenesis are needed. Chemoprevention represents a novel strategy for cervical cancer prevention. Our group plans phase I and II trials using α-difluoromethylornithine, a suicide inhibitor of ornithine decarboxylase and potent antiproliferative chemopreventive agent. We conducted a study to identify which polyamines in tissue could best serve as surrogate endpoint biomarkers for future trials. Thirty patients with biopsy-proven cervical intraepithelial neoplasia grade 3 underwent colposcopically directed biopsies of normal and abnormal areas of the uterine cervix for analysis of polyamine synthesis biomarkers. Statistically significant differences were found in the ornithine decarboxylase value and the spermidine:spermine ratio between normal and abnormal areas of the cervix. In general, the ranges in measurements varied widely. Differences in polyamine synthesis biomarkers between colposcopically normal and abnormal areas can be demonstrated. However, studies using polyamine synthesis biomarkers in the cervix would require large numbers of patients to achieve significance. J. Cell. Biochem. Suppls. 28/29:125-132. Published 1998 Wiley-Liss, Inc.This article is a US Government work and, as such, is in the public domain in the United States of America.
    Additional Material: 1 Ill.
    Type of Medium: Electronic Resource
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