Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In vitro studies have suggested that vitamin A lowers invasive potential of squamous cell carcinoma. Epidemiological data have also indicated that high dose vitamin A may improve survival in patients with previously resected lung carcinoma. To our knowledge, no studies have attempted to test the in vivo effect of vitamin A on the morphology and growth rate of lung and head and neck cancer. Freshly resected tumor cell suspensions were obtained by ex vivo fine needle aspiration and injected subcutaneously in duplicate in athymic male nude mice. Two to six weeks post-engraftment tests and controls were separated for each xenograft. Mice with test xenografts were given water soluble vitamin A (Aquasol ATM, Astra pharmaceutical, Westborough, MA, U.S.A) at a dose of 10,000 U/Kg/day intraperitoneally for 6 to 10 weeks (median 8 weeks). One to two hours prior to sacrifice bromodexouridine (BrdU) was injected intraperitoneally to assess the S-phase fraction in both test and control xenografts. Blood vitamin A levels in test and control animals were measured after sacrifice using high performance liquid chromatography (HPLC). Sections of test and control xenografts were routinely stained to assess morphologic differentiation and mitotic counts. Unstained sections of xenografts were immunostained by the antibody to BrdU to test for BrdU labeling index (BLI) reflecting S-phase fraction (SPF) and also by the MIB-1 antibody to assess proliferative activity. Eighteen tumors were studied. These included 9 squamous cell carcinomas of the lung, 5 squamous cell carcinomas of the head and neck, and 4 adenocarcinomas of the lung. Blood levels of vitamin A in test animals were 7 to 23 times those of the control animals (median 13 times). Neovascularization of the xenografts was seen in all cases. The morphology and mitotic activity of the test and control xenografts showed no significant difference. SPF and proliferative activity measured by BrdU and MIB-1 immunolabelling respectively showed no significant difference between test and control xenografts. Our study suggests that there is no significant in vivo effect of high dose vitamin A on the morphology and growth rate of xenografted non small cell carcinoma of the lung or squamous cell carcinoma of the head and neck.
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PMID:The effect of high dose vitamin A on the morphology and proliferative activity of xenograft lung and head and neck cancer. 879 35

Ataxia-telangiectasia (A-T) is a multisystem recessive disease characterized clinically by cerebellar ataxia, oculocutaneous telangiectasias, immunodeficiency, sensitivity to radiomimetic agents, and cancer predisposition. This pleiotropic disorder is caused by mutations in the ATM (mutated in A-T) gene, which is located in the human chromosomal region 11q22-q23. The ATM gene product is a member of a novel family of large proteins implicated in the regulation of the cell cycle and response to DNA damage. Heterozygosity for A-T was previously suggested to be associated with an increased risk of tumors, particularly female breast cancer. Because of loss of constitutional heterozygosity at 11q22-q23 is a frequent event in breast and other tumors, suggesting the presence of a tumor suppressor gene(s) in this region, we screened blood DNA samples from 88 unrelated breast cancer patients of Swedish cancer families for ATM mutations using single-strand conformation polymorphism analysis. All patients had a family history of tumors previously associated with A-T heterozygosity or homozygosity. We demonstrate the first three germ-line mutations in ATM identified by screening of breast cancer patients. Two mutations were previously found in A-T homozygotes and one mutation was a 1-bp insertion. All mutations were found in families with a large number of tumors, however, they did not cosegregate with malignancies. Although the proportion of A-T carriers in this sample seems to be higher than expected by chance, larger studies and pooled data sets will be required to establish that an A-T allele confers cancer susceptibility in heterozygotes.
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PMID:ATM mutations in cancer families. 879 79

Breast-carcinoma development presumably results from multiple mutational events in tumor-associated genes. Certain results indicate that some tumor-suppressor genes may combine their pathogenetic potential to synergistically promote tumor growth. In an effort to identify such mechanisms in breast tumors, a series of 77 (group I) paired blood tumor samples from patients with sporadic mammary carcinomas was analyzed for loss of heterozygosity with 15 polymorphic markers on the chromosomal arms 7q, 11q, 13q, 16q, 17p and 17q. A significant association was observed for the combination of allelic losses on chromosomes 11q and 16q. In order to confirm these findings, we studied a second independent series of 189 breast-tumor patients (group 2) with comparable histopathological tumor stages. Group 2 was examined for the same genetic alterations using the identical set of polymorphic markers. The data from this group confirmed the detected association of loss of heterozygosity on chromosomes 11q and 16q and indicate the cooperation of putative tumor-suppressor genes on the chromosomal arms 11q and 16q in a sub-set of breast carcinomas. The regions involved harbor the candidate genes ATM (mutated in ataxiatelangiectasia) on chromosome 11q23 and UVO (uvomorulin, cadherin E) and BBCI (breast basic conserved I) on chromosome 16q22-q24.
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PMID:Association of allelic losses on human chromosomal arms 11Q and 16Q in sporadic breast cancer. 879 73

The p53 gene product is part of a pathway regulating growth arrest at the G1 checkpoint of the cell cycle. Mutation of other components of this pathway, including the products of the ataxia telangiectasia (AT), GADD45, mdm2, and p21WAF1/CIP1 genes may have effects comparable to mutations in the p53 gene. The GADD45 gene is induced by ionizing radiation and several DNA-damaging xenobiotics. Induction requires the binding of wild-type p53 to an evoulutionarily highly conserved putative intronic p53 binding site in intron 3 of GADD45. We recently analyzed the entire coding region of the p53 gene in primary breast cancers of Midwestern white women and found 21 mutations among 53 tumors (39.6%). We now have shown by direct sequencing that there are no mutations in the intronic p53 binding site of the GADD45 gene in any of the 53 primary breast cancers and no mutations in the entire coding region of the GADD45 gene in a subset of 26 consecutive tumors (12 with p53 mutation and 14 without p53 mutation). The only sequence variation detected was a common polymorphism in intron 3. The absence of mutations in the GADD45 gene, including the putative p53-binding intronic site, suggests that this gene is not a frequent target of mutations in breast cancer. Although mutations of the p53 gene have been studied in a wide spectrum of human cancers, GADD45 has not been examined in any tumor or cell line to the best of our knowledge. Our results raise the possibility that mutation of the GADD45 gene alone is not functionally equivalent to loss of wild-type p53 activity.
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PMID:A polymorphism but no mutations in the GADD45 gene in breast cancers. 883 60

ATM, the gene mutated in the inherited human disease ataxia-telangiectasia, is a member of a family of kinases involved in DNA metabolism and cell-cycle checkpoint control. To help clarify the physiological roles of the ATM protein, we disrupted the ATM gene in mice through homologous recombination. Initial evaluation of the ATM knockout animals indicates that inactivation of the mouse ATM gene recreates much of the phenotype of ataxia-telangiectasia. The homozygous mutant (ATM-/-) mice are viable, growth-retarded, and infertile. The infertility of ATM-/- mice results from meiotic failure. Meiosis is arrested at the zygotene/pachytene stage of prophase I as a result of abnormal chromosomal synapsis and subsequent chromosome fragmentation. Immune defects also are evident in ATM-/- mice, including reduced numbers of B220+CD43- pre-B cells, thymocytes, and peripheral T cells, as well as functional impairment of T-cell-dependent immune responses. The cerebella of ATM-/- mice appear normal by histologic examination at 3 to 4 months and the mice have no gross behavioral abnormalities. The majority of mutant mice rapidly develop thymic lymphomas and die before 4 months of age. These findings indicate that the ATM gene product plays an essential role in a diverse group of cellular processes, including meiosis, the normal growth of somatic tissues, immune development, and tumor suppression.
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PMID:Targeted disruption of ATM leads to growth retardation, chromosomal fragmentation during meiosis, immune defects, and thymic lymphoma. 884 91

We have surveyed the sensitivity of the spin lattice relaxation rates of the 19F resonances of several perfluorocarbons to changes in oxygen tension and temperature. Hexafluorobenzene was found to exhibit exceptional sensitivity to changes in oxygen tension, and we have exploited this phenomenon to measure tumor oxygen tension following intratumoral injection. When 20 microliters hexaflourobenzene were injected they remained localized and the biodistribution was readily assessed on the basis of combined 1H and 19F three-dimensional MRI. Relaxation measurements indicated a typical baseline oxygen tension of 4.0 +/- 1.5 torr in the central region of a Dunning prostate R3327-AT1 tumor when the rat breathed 66% oxygen. Altering the inspired oxygen concentration to 100% produced a modest increase in pO2 (5.6 +/- 0.7 torr; p < 0.1). Significantly, the precision of these measurements should facilitate NMR investigations of radiobiological hypoxia. Intra-tumoral injection allowed measurements from regions not normally accessible to infused perfluorocarbons and provides an additional approach to measuring tumor oxygenation.
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PMID:Hexafluorobenzene: a sensitive 19F NMR indicator of tumor oxygenation. 889 99

Murine models of human carcinogenesis are exceedingly valuable tools to understand genetic mechanisms of neoplastic growth. The identification of recurrent chromosomal rearrangements by cytogenetic techniques serves as an initial screening test for tumour specific aberrations. In murine models of human carcinogenesis, however, karyotype analysis is technically demanding because mouse chromosomes are acrocentric and of similar size. Fluorescence in situ hybridization (FISH) with mouse chromosome specific painting probes can complement conventional banding analysis. Although sensitive and specific, FISH analyses are restricted to the visualization of only a few mouse chromosomes at a time. Here we apply a novel imaging technique that we developed recently for the visualization of human chromosomes to the simultaneous discernment of all mouse chromosomes. The approach is based on spectral imaging to measure chromosome-specific spectra after FISH with differentially labelled mouse chromosome painting probes. Utilizing a combination of Fourier spectroscopy, CCD-imaging and conventional optical microscopy, spectral imaging allows simultaneous measurement of the fluorescence emission spectrum at all sample points. A spectrum-based classification algorithm has been adapted to karyotype mouse chromosomes. We have applied spectral karyotyping (SKY) to chemically induced plasmocytomas, mammary gland tumours from transgenic mice overexpressing the c-myc oncogene and thymomas from mice deficient for the ataxia telangiectasia (Atm) gene. Results from these analyses demonstrate the potential of SKY to identify complex chromosomal aberrations in mouse models of human carcinogenesis.
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PMID:Multicolour spectral karyotyping of mouse chromosomes. 889 61

The authors present a clinical case of leiomyoma, localized in the anterior margin of the masticator muscle. The clinical diagnosis was formulated following the histological test on the operating part. It is a case a rare pathology of the oral cavity that isn't commonly suspected. The symptoms of the patient let think a pathology of ATM and it was not typical of benign or malign neoplasm of the soft tissue of oral cavity. Only the use of a special clinical test, permitted the possibility to diagnose the exceptional case of masseter muscle on the left. The surgical therapy, being the neoplasm case benign and well capsuled resulted to be treatable and permitted the definitive resolution of the case.
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PMID:[Leiomyoma of the masseter muscle. Report of a case]. 896 74

To appreciate the involvement of known or potential susceptibility genes in sporadic breast tumors, we have searched for chromosomal deletions by studying loss of heterozygosity (LOH) at 43 microsatellite (CA)n markers from human chromosomes 10, 11 and 17, in 115 unselected consecutive samples of breast carcinoma with particular emphasis on specific regions. No site of consistent LOH was identified on chromosome 10. Five regions of LOH were contained within bands q22-24 of chromosome 11 for which nearly 50% of the tumors had LOH at at least one marker. This region is thus a major site of deletion in breast cancer and several tumor suppressor genes seem to be involved. One of them may be the ataxia telangiectasia (ATM) gene which is located in one of the affected regions. Five regions of LOH, one of which is within the BRCA1 gene area, were recognized along chromosome 17. LOH at three of these regions were found in highly proliferative tumors. When combined with a previous study of chromosome 13 with emphasis on BRCA2 and Rb1 genes, this work allowed to distinguish a total of 12 regions of LOH, variably affected in breast tumors and correlated with prognostic parameters.
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PMID:Loss of heterozygosity in human breast carcinomas in the ataxia telangiectasia, Cowden disease and BRCA1 gene regions. 901 20

A simplified model for tumorigenesis, locoregional growth, and metastases is proposed for carcinoma of the cervix. With the use of this model, four potential areas for future directions for radiobiologic-clinical research are identified. The first area concerns the influence of human papillomavirus infection and p53 mutations on tumor biology, with particular reference to radiosensitivity and metastatic potential. Research in this area should be most fruitful. The second area focuses on the influence of hypoxia on clinical outcome in carcinoma of the cervix. The use of selective hypoxic cell toxins (e.g., tirapazamine) for phase II testing in hypoxic tumors is recommended. The third area concerns the development and clinical confirmation of assays for the prediction of intrinsic tumor radiosensitivity (e.g., surviving fraction after 2 Gy) and normal tissue radiosensitivity. The need exists for more rapid assays so that their results can be available prior to institution of therapy. The influence of the intrinsic radiosensitivity of normal tissues (especially in patients who are heterozygotes for ataxia-telangiectasia and patients with autoimmune disease) may permit identification of those at increased risk for complications so that alternative, less toxic treatment can be allocated. The fourth area for additional study concerns the influence of both intrinsic (c-myc amplification, matrix metalloproteinase levels) and extrinsic factors (fever, immunosuppression) on the development of distant metastases. Such investigations will permit identification of patients at high risk of developing distant metastases so that adjuvant treatments (e.g., chemotherapy or metalloproteinase inhibitors) can be explored. It is believed that future clarification of our proposed model will lead to other worthwhile areas for therapeutic intervention.
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PMID:New directions for radiation biology research in cancer of the uterine cervix. 902 43


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