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  • 1
    Electronic Resource
    Electronic Resource
    Inhibition of proliferation and induction of apoptosis in cervical carcinoma cells by retinoids: Implications for chemoprevention (1995)
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 59 (1995), S. 80-86 
    Details
    ISSN: 0730-2312
    Keywords: Apoptosis ; cervical cancer ; chemoprevention ; N-(4-hydroxyphenyl)retinamide ; retinoids ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: The effects of retinoids including all-trans-retinoic acid (ATRA), 13-cis-retinoic acid (13CRA), and N-(4-hydroxyphenyl)retinamide (4-HPR) on several cervical carcinoma cell lines in culture were investigated as a prelude to investigating the mechanisms underlying the chemopreventive potential of retinoids in cervical cancer. We found that when used at a concentration of 1 μM, 13CRA and ATRA inhibited the proliferation of three cell lines (ME-180 [HPV 68], SiHa [HPV 18], and HT-3 [HPV-]) by about 80% after a seven-day treatment. Three other cell lines (MS-751 [HPV 18], HeLa [HPV 18], C-33A [HPV-]) were moderately inhibited (30-48%), and two (C-4 II [HPV 18], CaSki [HPV 16]) responded poorly (〈 25% inhibition). 4-HPR failed to inhibt the growth of any of these cell lines when used at 1 μM; however, when used at 5 or 10 μM, it induced apoptosis as evidenced DNA fragmentation in several of the cell lines and was more potent in this effect than 10 μM ATRA. Retinoids that induce apoptosis in malignant cells may be able to exert similar effects on premalignant cells. Such retinoids would be expected to exhibit greater potency as chemopreventive agents than retinoids that exert only cytostatic effects.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcb.240590911
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  • 2
    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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  • 3
    Electronic Resource
    Electronic Resource
    Micronuclei: A potential intermediate marker for chemoprevention of aerodigestive tract cancer (1993)
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 53 (1993), S. 250-254 
    Details
    ISSN: 0730-2312
    Keywords: chemoprevention ; intermediate markers ; micronuclei ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Because they may be used as a quantifiable estimate of the extent of recent DNA injury, micronuclei, extrachromosomal fragments of DNA, are among the most studied potential intermediate markers of cancer chemoprevention. Serial measurements of micronuclei frequency may be easily performed on scrapings from the oral cavity or on bronchial brushings. Assessment of micronuclei frequency and its response to chemopreventive agents has been incorporated into studies of upper aerodigestive tract and lung cancer chemoprevention. These studies have helped define the characteristics of micronuclei and have suggested a role for this test in future chemoprevention studies. Micronuclei frequency has been shown to be increased in the oral and bronchial mucosa of individuals with known carcinogen exposure and is higher at the site of the greatest carcinogen exposure, such as the site where tobacco quids are held, than in grossly normal-appearing mucosa. Treatment with chemopreventive agents leads to a reduction in micronuclei frequency. In oral leukoplakia studies, this effect followed treatment with β-carotene, retinol, α-tocopherol, and 13-cis-retinoic acid. The multistep process of epithelial carcinogenesis results from DNA damage and specific genetic events. That micronuclei reflect ongoing DNA injury suggests the hypothesis that long term suppression of cellular genotoxicity, as reflected by a reduction in micronuclei frequency, ultimately leads to a reduction in cancer incidence.
    Additional Material: 1 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcb.240531037
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  • 4
    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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