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  • 1
    ISSN: 1520-4995
    Source: ACS Legacy Archives
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 554 (1989), S. 0 
    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: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] To better understand genetic alterations in oral premalignant lesions, we examined 84 oral leukoplakia samples from 37 patients who had been enrolled in a chemoprevention trial. The samples were analyzed for two microsatellite markers located at chromosomes 9p21 and 3p14. Loss of heterozygosity ...
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0886
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Prematurely condensed chromosomes (PCC) of HeLa cells synchronized in different phases of the cell cycle were analyzed by high-resolution scanning electron microscopy. The purpose of this study was to examine changes in the arrangement of the basic 30-nm chromatin fiber within interphase chromosomes associated with progression through the cell cycle. These studies revealed that highly condensed metaphase chromosomes and early G1-PCC consisted of tightly packed looping fibers. Early to mid G1-PCC were more extended and exhibited gyres suggestive of a despiralized chromonema. Further attenuation of PCC during progression through G1 was associated with a gradual transition from packed looping fibers to single extended longitudinal fibers. This process occurs prior to the initiation of DNA synthesis which appears to be localized within single longitudinal fibers. Following replication of a chromosome segment, extended longitudinal fibers were rapidly reorganized into packed looping fiber clusters concomitant with the formation of a multifibered chromosome axis. This results in the characteristic “pulverized” appearance of S-PCC when viewed by light microscopy. Subsequently, adjacent looping fiber domains coalesce, resulting in the uniformly packed, looping fiber arrangement observed in G2-PCC. Spiralization of the chromonema during the G2-mitotic transition results in the formation of highly compact metaphase chromosomes.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1573-7217
    Keywords: breast cancer ; in situ hybridization ; interphase cytogenetics ; paraffin-embedded sections ; multistep carcinogenesis ; tumor cytogenetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Fluorescentin situ hybridization techniques have provided an important tool for interphase cytogenetic studies of human neoplasms. However, these techniques are difficult to use on formalin-fixed archival tissue sections. We describe here a non-fluorescent, non-isotopicin situ hybridization (ISH) approach that is easily applicable to paraffin-embedded breast tissue sections. The technical steps that must be monitored and individualized to optimize signal generation and detection are discussed. This ISH technique has several advantages over fluorescent detection methods. The signal obtained can be viewed using an ordinary light microscope and does not fade with time. More importantly, the signal is observed and analyzed in the context of tissue morphology. The technique permits detection of numerical chromosomal abnormalities not only in malignant but also in apparently normal and potentially premalignant mammary tissue. This may allow identification of focal genetic abnormalities as well as field-defects and enable analysis of their evolution during the multistep transformation to mammary neoplasm. This technique is also suitable for analysis of tumor heterogeneity and the correlation of numerical chromosomal aberrations with histologic, immunocytochemical, and clinical features of breast tumors.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 95 (1978), S. 333-341 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The object of this study was to develop a map of G1 phase on the basis of the progressive changes taking place in the morphology of the prematurely condensed chromosomes as the cells traverse through G1 and then use this technique to determine the cell cycle location of normal and transformed cell populations in plateau phase. The morphology of the prematurely condensed chromosomes (PCC) of G1 cells in random populations was found to be highly variable. For a better understanding of the relationship between the morphology of the G1-PCC and their position within G1 phase, synchronized populations of Chinese hamster ovary (CHO) cells in early, mid-, and late G1 phase were fused with mitotic cells. Early G1 cells resulted in highly condensed G1-PCC, while late G1 cells gave very extended G1-PCC. Mid-G1 cells resulted in PCC of intermediate condensation. To test the validity of these criteria for mapping the position of a cell in the cell cycle, synchronous G1 cell populations were treated with a variety of metabolic inhibitors. Cycloheximide and actinomycin D were shown to block cell in early G1 phase, while excess thymidine and hydroxyurea blocked cells in early S phase. The results presented here indicate that, upon reaching plateau phase, normal cell populations (BALB-C mouse 3T3, human PA-2, and WI 38) stop in early G1, while most cells in transformed cell lines (CHO, HeLa, and mouse SV-3T3) accumulate in late G1.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 63 (1996), S. 57-62 
    ISSN: 0730-2312
    Keywords: cancer risk ; genetic instability ; in situ hybridization ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Many human tumors are thought to develop along a multistep pathway in tissues that have encountered long periods of carcinogen exposure and thus have accumulated genetic hits in functional targets relevant to tumor evolution. The cumulative degree of genetic change is dependent on both exogenous (e.g., degree of carcinogen exposure) and endogenous factors (e.g., metabolism of procarcinogens, repair or misrepair capacity, proliferation properties of the tissue, capability of damaged cells to survive). Thus one approach to risk estimation is to measure the accumulated amount of genetic damage in a target tissue at risk for tumor development. Since one cannot predict the exact site of the future tumor, the risk assay must detect a generalized ongoing process of genetic instability from small, random biopsies. The technique of chromosome in situ hybridization involves the use of chromosome- or region-specific probes and provides an ability to directly visualize genetic change (e.g., random or clonal chromosome polysomy and monosomy) on thin tissue sections (where tissue architecture is maintained) or exfoliated cells. Analyses of normal and premalignant lesions adjacent to tumors (e.g., head and neck, lung, bladder, cervix, breast) have demonstrated that chromosome instability can be detected in the field of the tumor (i.e., in normal and premalignant cells in a tissue at 100% risk of tumor development) and the degree of chromosome instability increases with the degree of histologic progression toward cancer. Analyses of premalignant lesions (e.g., oral leukoplakia and erythroplakia from individuals at risk for aerodigestive tract cancer) by chromosome in situ hybridization have uncovered varying degrees of chromosome instability. However, approximately half of those individuals who showed a high degree of chromosome instability in biopsies subsequently developed aerodigestive tract cancer. Of interest, half of these tumors have developed away from the biopsied site, suggesting that the detection of a chromosome instability process in one aspect of the tissue might yield risk information for the total tissue field. These studies also suggest that chromosome in situ hybridization might be useful for identifying individuals with high tumor risk who might benefit from chemopreventive intervention. J. Cell. Biochem. 25S:57-62. © 1997 Wiley-Liss, Inc.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
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  • 8
    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
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  • 9
    Electronic Resource
    Electronic Resource
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 67 (1997), S. 125-132 
    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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  • 10
    Electronic Resource
    Electronic Resource
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 53 (1993), S. 233-236 
    ISSN: 0730-2312
    Keywords: head and neck cancer ; leukoplakia ; in situ hybridization ; field cancerization ; multistep carcinogenesis ; polysomy ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Upper aerodigestive tract tumorigenesis has been hypothesized to represent a field cancerization process with multistep events based on its association with known carcinogens, its frequent associated premalignant lesions, and its multifocal clinical manifestation. To further explore this working hypothesis, we have examined normal tissue and premalignant lesions in the field of tumors for evidence of genetic change. Paraffin sections of head and neck tumors harboring neighboring premalignant lesions were explored for the presence of chromosome polysomies using in situ hybridization and chromosome-specific centromeric probes. Cell exhibiting random polysomy were observed in the premalignant regions near the tumors. The frequency of polysomy in the tumor field increased as the tissue progressed from normal morphology (33%), to hyperplasia (67%), to dysplasia (95%), and to squamous cell carcinoma (96%). These results support the notions of field cancerization and multistep tumorigenesis in the aerodigestive tract. To determine whether the degree of accumulated genetic alterations might serve as a biomarker for risk of developing malignancy, a set of biopsies of oral premalignant lesions (leukoplakia, erythroplakia) were retrospectively chosen for polysomy analysis from two groups of individuals: one group who subsequently developed oral cancer and one group who did not develop oral cancer. Three of the five individuals who showed significant chromosome polysomies in their biopsies subsequently developed oral cancer, whereas only one of eight individuals with little evidence of polysomy subsequently progressed to oral cancer. These results suggest that evidence of generalized genetic change or instability might be useful as a genetic biomarker for risk assessment.
    Additional Material: 1 Tab.
    Type of Medium: Electronic Resource
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