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  • 1
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Cell lines of non-small cell lung cancer (nonSCLC) have been shown to contain activating mutation of the K-ras oncogene in about 30% of cases, whereas no small cell lung cancer (SCLC) cell lines displayed these mutations. Biochemically, these mutations result in the ras gene product (p21) being constitutively activated in its GTP-bound form and insensitive to the hydrolytic action of the ras-specific GTPase-activating protein (ras GAP). We hypothesized that, if tumor development is related to the p21 ras being in the active GTP-bound state, then a similar malignant phenotype may result from an inactivating mutation in the ras GAP gene in the region that interacts with ras p21 (so-called catalytic domain). To test this hypothesis, we screened a panel of SCLC and non-SCLC cell lines for major genetic alterations in the catalytic domain of the GAP gene with the Sothern blot technique, and for minor genetic abnormalities (e.g., point mutations) with denaturing gradient gel electrophoresis and single-strand conformation polymorphism. Mutations in the catalytic domain of the GAP gene could not be demonstrated by any technique in any cell line examined. We conclude that mutational inactivation of the catalytic domain of the GAP gene probably does not contribute to the development of lung cancer.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Somatic alterations in cellular DNA underlie almost all human cancers. The prospect of targeted therapies and the development of high-resolution, genome-wide approaches are now spurring systematic efforts to characterize cancer genomes. Here we report a large-scale project to characterize ...
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 262 (1976), S. 696-698 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Here we describe the marked elevation of ODC levels which occurs in murine sarcoma virus (MSV)-infected cells. The continuous, contact inhibited, non-tumorigenic cell line BALB/3T3 (ref. 9) was used for these studies because it has a short doubling time and is readily transformed by MSV. Gz-MSV ...
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pathology: Mechanisms of Disease (2006) 1 (2006), S. 331-348 
    ISSN: 1553-4006
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine
    Notes: From histological and biological perspectives, lung cancer is a complex neoplasm. Although the sequential preneoplastic changes have been defined for centrally arising squamous carcinomas of the lung, they have been poorly documented for the other major forms of lung cancers, including small cell lung carcinoma and adenocarcinomas. There are three main morphologic forms of preneoplastic lesions recognized in the lung: squamous dysplasias, atypical adenomatous hyperplasia, and diffuse idiopathic pulmonary neuroendocrine cell hyperplasia. However, these lesions account for the development of only a subset of lung cancers. Several studies have provided information regarding the molecular characterization of lung preneoplastic changes, especially for squamous cell carcinoma. These molecular changes have been detected in the histologically normal and abnormal respiratory epithelium of smokers. Two different molecular pathways have been detected in lung adenocarcinoma pathogenesis: smoking-associated activation of RAS signaling, and nonsmoking-associated activation of EGFR signaling; the latter is detected in histologically normal respiratory epithelium.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Physiology 64 (2002), S. 681-708 
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Abstract Lung cancer is the most common cause of cancer death in the United States, killing more than 156,000 people every year. In the past two decades, significant progress has been made in understanding the molecular and cellular pathogenesis of lung cancer. Abnormalities of proto-oncogenes, genetic and epigenetic changes of tumor suppressor genes, the role of angiogenesis in the multistage development of lung cancer, as well as detection of molecular abnormalities in preinvasive respiratory lesions, have recently come into focus. Efforts are ongoing to translate these findings into new clinical strategies for risk assessment, chemoprevention, early diagnosis, treatment selection, and prognosis and to provide new targets and methods of treatment for lung cancer patients. All these strategies should aid in reducing the number of newly diagnosed lung cancer cases and in increasing the survival and quality of life of patients with lung cancer.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-1335
    Keywords: Non-small-cell lung cancer ; Squamous cell carcinoma ; Loss of heterozygosity ; Chromosome 9
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We analyzed 87 Japanese non-small-cell lung carcinomas (NSCLC), including 30 squamous cell, 51 adenocarcinomas and 6 large-cell carcinomas for loss of heterozygosity (LOH) on the short arm of chromosome 9, and we correlated our findings with clinicopathological features. We used four polymorphic microsatellite markers on 9p (interferon A gene, D9S171, D9S126, and D9S169), which flank the critical region (9p21-22) involved in lung cancer. We observed alterations of DNA sequences at 9p in NSCLC (27 of 82 informative cases or 33%). Concordance among the four markers was high (87%), indicating that the deletions often were relatively large. The 27 genetic alterations observed on 9p include 26 examples of LOH, 1 homozygous deletion, and 1 case with LOH and evidence of microsatellite alteration characterized by shift in band mobility. We noted a high frequency of LOH at 9p especially in, squamous cell carcinoma (17 of 29 informative cases or 59%) and in poorly differentiated NSCLC (12 of 23 informative cases or 52%). There was no correlation between LOH at 9p and the other clinical parameters, including survival, gender, tumor size and the presence of regional or distant metastases. In contrast to other reports we found only rare instances of homozygous deletions (1%) and microsatellite alteration showed as a mobility shift (1%). Our findings demonstrate that LOH at the short arm of chromosome 9 is correlated with squamous cell and poorly differentiated carcinomas in Japanese patients with NSCLC.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1573-7217
    Keywords: breast cancer ; in vivo tumor models ; Her-2/neu ; metastasis ; SCID mice ; soluble Her-2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract HER-2/neu is overexpressed on a variety of human adenocarcinomas and overexpression has been associated with a poor prognosis. For this reason, HER-2 has become an attractive target for immunotherapy. To facilitate testing of anti-HER-2-monoclonal antibodies (MAbs) and immunotoxins (ITs), we have evaluated the in vivo growth and metastatic spread of three HER-2-overexpressing human breast cancer cell lines (BT474, MDA-MB-453 and HCC1954) and one ovarian cancer cell line (SKOV3.ip1) in pre-irradiated male SCID mice using subcutaneous (s.c.), intravenous (i.v.) and intraperitoneal (i.p.) routes of injection. All the cell lines tested grew as s.c. tumors and the growth of BT474 and MDA-MB-453 cells after s.c. injection was improved by co-inoculation with Matrigel. Metastases to the lungs were detectable by PCR or histopathology after s.c. injection of BT474 and to a much lesser extent after s.c. injection of HCC1954, MD-MB-453 and SKOV3.ip1cells. I.P. injection of HCC1954 and SKOV3.ip1 cells produced fatal ascites while i.v. injection of SKOV3.ip1, but not BT474 or MDA-MB-453 cells, resulted in infiltration of lungs and death within 9–11 weeks.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Our laboratory has established and characterized several human lung cancer cell lines for their histological, amine precursor uptake and decarboxylation (APUD) and karyotypic properties (Table I)10, There are two major classes of lung cancer: non-small cell lung cancers (NSCLC) which ...
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] While examining genomic DNA from human SCLC cell lines for evidence of c-myc and N-myc amplification, we occasionally observed a number of additional EcoRl fragments, including 10.0- and 6.6-kb fragments that hybridized to either a second-exon c-myc probe14 or to the homologous region of the N-myc ...
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Accurate molecular analysis of tumors and their precursor lesions requires the extraction of specific subpopulations of cells (normal, preneoplastic and tumor) from a composite background of multiple cell types. Attempts to obtain pure tumor cell samples have resulted in the genesis of several ...
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