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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ataxia telangiectasia (AT) is a primary immunodeficiency syndrome characterized by oculocutaneous telangiectasia, ataxia, recurrent infection and development of malignancies. Epstein-Barr virus (EBV) is a B-cell lymphocytotropic virus which causes infectious mononucleosis and is also highly associated with Burkitt's lymphoma, nasopharyngeal carcinoma and lymphoproliferative disorders in immunodeficient patients. 10 Japanese patients with AT were studied concerning the status of EBV infection by specific EBV serology, and reactivity of peripheral lymphocytes to EBV. All the AT patients had high EBV antibody titers of IgG to viral capsid antigen (VCA) and early antigen (EA), while low titers of IgG to EBV-associated nuclear antigen (EBNA), compared with age and sex matched healthy controls. However, significant differences were not apparent with antibodies to several other viruses between the AT patients and controls. These antibody characteristics were thought to be that an activated EBV infection occurred in AT patients. Then the lymphocytes were exposed to B95-8 strain EBV. There was no significant differences in EBNA induction frequency at 24 hours prior to cellular DNA synthesis, between the AT and controls. EBV-specific T cell killer function was very low as judged with the days of establishment of lymphoblastoid cells expressing EBNA on all cells after EBV exposure, when compared with the lymphocytes from controls. These AT lymphoblastoid cells easily expressed EA and VCA by cultivation at lower temperature of 33 degrees C, 12-0-tetradecanoyl-phorbol-13-acetate treatment, 60Co irradiation and by P3HR-1 strain EBV infection. Malignant transformation with high colony forming efficiency in soft agarose and tumor formation in nude mice easily occurred with some of AT lymphoblastoid cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Studies on Epstein-Barr virus (EBV) infection and reactivity of peripheral B lymphocytes to EBV in patients with ataxia telangiectasia]. 301 55

Three human T-cell clones with activated killer activity (5B5, 5C1, and 7B5) which could lyse various tumor cell lines were established. The cytotoxic activity of these clones was decreased by incubation with anti-CD3 monoclonal antibody, suggesting that they recognized tumor cells by T-cell antigen receptor. A monoclonal antibody which blocked the cytotoxic activity of clone 5B5 was obtained. This antibody (N1977) blocked the binding and cytotoxic activity of clone 5B5 at the target cell level, suggesting that the antigen defined by N1977 antibody, designated as ATM-1, was a target molecule recognized by 5B5 cells. ATM-1 in the conditioned medium of a cancer cell line (NBT-2) and serum from a patient with lung cancer was characterized by following its immunoreactivity. On gel filtration, both the conditioned medium and the serum gave three peaks of ATM-1 immunoreactivity, corresponding to approximate molecular weights of 1,200,000, 700,000, and 120,000, respectively. They were chromatofocused at pH 4.0, 4.8, and 6.5, respectively. The high molecular weight forms were shown to be molecules with the disulfide-linked elementary glycoprotein with ATM-1 immunoreactivity and approximate molecular weight of 120,000. Most of the molecules with ATM-1 immunoreactivity bound to both concanavalin A and wheat germ agglutinin, and their binding activity to the antibodies was lost by treatment at 60 degrees C for 30 min. An assay of ATM-1 level in sera was performed by a sandwich enzyme immunoassay. The following positive percentages were obtained from preliminary clinical studies: breast cancer, 67% (8 of 12 cases); hepatocellular carcinoma, 83% (10 of 12 cases); gastric cancer, 58% (7 of 12 cases); lung cancer, 41% (5 of 12 cases); hematological malignancies, 0% (0 of 9 cases); systemic lupus erythematosus, 0% (0 of 8 cases); rheumatoid arthritis, 0% (0 of 8 cases).
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PMID:Identification of a tumor-associated target antigen, ATM-1, for a human T-cell clone with activated killer activity and its existence in sera of cancer patients. 304 79

Steady-state levels of c-Ha-ras mRNA were measured in eight sublines of the Dunning R3327 rat prostatic adenocarcinoma. As a control, normal dorsal prostate tissue was studied. Increased expression of c-Ha-ras is associated with tumor progression in one lineage of the Dunning R3327 system (H to AT1 to MAT-Lu and MAT-Ly-Lu). Here ras mRNA increases as the tumor advances from androgen dependence and a high degree of differentiation to an anaplastic aneuploid phenotype with high metastatic potential. However, in the other Dunning lineage (H to HI to HI-F to AT3), expression of c-Ha-ras is variable and does not correlate with tumor progression. Immunocytochemistry showed that levels of the c-Ha-ras p21 protein paralleled steady-state mRNA levels in variants. Transfection assays, using NIH/3T3 cells, suggested that the ras loci were not activated in the R3327 tumors. Levels of c-Ki-ras mRNA were also measured in the Dunning tumors; these did not correlate with tumor progression in either lineage. Expression of N-ras mRNA was not detected in the Dunning tumors.
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PMID:Expression of ras proto-oncogenes in the Dunning R3327 rat prostatic adenocarcinoma system. 306 50

An increased incidence of malignancies occurs in ataxia telangiectasia. These are most frequently hematopoietic in children and epithelial in adults. Both cellular immunodeficiency and chromosome damage have been implicated in their etiology. There has been only one report of a salivary malignancy, a parotid mucoepidermoid carcinoma. We describe a second salivary malignancy, a metastasizing acinic cell carcinoma of the parotid gland, that developed in a 33-yr-old woman with ataxia telangiectasia. The marked chromosomal abnormalities that were present may have been involved in the pathogenesis of her tumor.
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PMID:Ataxia telangiectasia and acinic cell carcinoma of the parotid gland. 317 93

Cytogenetic abnormalities involving chromosome 14 band q32 are consistently observed in human T-cell tumors. Patients with ataxia-telangiectasia (AT) are especially prone to development of these tumors, which frequently carry either inversion inv(14)(q11;q32) or translocation t(14;14) (q11;q32) chromosomes. We have previously shown that the cytogenetic breakpoints of one t(14;14)(q11;q32) chromosome and two inv(14)(q11;q32) chromosomes in T-cell tumors from AT and non-AT patients join the T-cell receptor alpha chain locus, at chromosome band 14q11, with a region(s) at 14q32 centromeric of the immunoglobulin heavy chain variable region (VH) gene IGHV. We now show that these two inv(14) breakpoints are linked by 2.1 kb of germ-line 14q32 DNA and that the three breakpoints define, by in situ hybridization analysis, a single locus at chromosome band 14q32.1 located about 15-20 million base pairs on the centromeric side of the IGH locus. Sequence analysis of the 14q32.1 breakpoint regions indicates that abnormal recombination does not universally result from mistaken V-D-J joining (D = diversity region; J = joining region). Therefore, we invoke a tumor selection model to describe the role of the 14q32.1 locus in tumor development.
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PMID:Analysis of a T-cell tumor-specific breakpoint cluster at human chromosome 14q32. 319 18

At the beginning of this century Theodor Boveri predicted that specific chromosome changes would be found to have a causal role in neoplasia. We are now beginning to acquire the evidence to substantiate this hypothesis. The evidence comes from two particular sources, (i) genetic environmental interactions and (ii) specific constitutional chromosome aberrations. Cancer incidence varies throughout the world. This is often due to the interaction of an environmental agent with a genetically varied population. Using UV and ionising radiation as examples it is argued that some individuals are more susceptible to genetic damage by these agents. Moreover, the genetic lesions which are caused by these agents are now being shown to be relevant to cancer. In the radiosensitive syndrome ataxia-telangiectasia for example, specific chromosome rearrangements have been defined which seem likely to be directly involved in the development of leukaemia in these patients. The second line of evidence comes from the study of patients who have constitutional chromosome abnormalities associated with susceptibility to specific cancers. It has now been shown that these chromosome changes mark the location of genes which are involved in the development of cancer and that these same loci are also important in the non-familial forms of these diseases. Thus we are beginning to understand for the first time the mechanistic pathway that leads from environmental agents, through chromosome damage, to the alteration of specific genes which control the neoplastic process.
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PMID:Chromosomes and cancer families. 333 94

Human genotypes are known "that confer both increased susceptibility or resistance to DNA damage and increased cancer risk after exposure to carcinogenic agents, including ionizing radiation" (NAS 1980). The existence of sensitive subgroups at elevated risk, if they are of appreciable size, could have significant impact on the actual distribution of risk. The radiosensitive disorder ataxia-telangiectasia (A-T) serves as a good example: the significant "at risk" group, A-T heterozygotes, is estimated to comprise between 0.5% and 5% of the total population, and has a twofold elevated lifetime risk of fatal neoplasia. Other genetic syndromes that manifest abnormal radiosensitivity are also known, but no estimates are available for the population frequency of all such phenotypes, or for their overall degree of increased risk. As the first part of a program addressing these questions, we have developed a rapid and inexpensive assay for screening members of the general population for abnormal radiosensitivity; such persons would be regarded as at presumptive elevated risk of radiogenic cancer. Our method utilizes lymphoblastoid cell lines and chronic as opposed to acute gamma-ray exposure to amplify the difference between normal and somewhat sensitive strains. A simple "grow-back" assay assesses the survival response. Information on the extent of natural variation in inherited susceptibility to radiogenic cancers could be most useful for radiation protection in the future.
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PMID:Impact on radiogenic cancer risk of persons exhibiting abnormal sensitivity to ionizing radiation. 341 Jul 13

Dose response curves were obtained for normal human fibroblasts and for several cell lines derived from human tumors, including melanomas and an osteosarcoma. Most of the tumor lines are similar in radiosensitivity to the normal fibroblasts, except for the melanoma lines, which are significantly more resistant. The two melanoma lines differ, one being much more radioresistant than the other. Potentially lethal damage repair (PLDR) has been studied in these cell lines as well. The extent of PLDR does not appear to correlate with radioresistance; for example, the most resistant melanoma line shows very little repair of PLD. In addition, the normal fibroblasts repair PLD at least as well as any of the tumor derived lines, which casts doubts on the wisdom of introducing into clinical practice inhibitors of PLD until a clear differential between normal tissues and tumors has been demonstrated in vivo. Low dose-rate studies with normal human fibroblasts indicate a smaller dose-rate effect than for most established cell lines of rodent origin. Indeed, in the human cells studied, the effect of sublethal damage repair is quantitatively similar to the repair of potentially lethal damage. Dose response curves for acute and protracted exposures have been obtained for cells derived from patients with cancer-prone syndromes including ataxia telangiectasia (AT) and Bloom's syndrome. Both cell lines are much more radiosensitive than normal human fibroblasts; the AT cells show a dose-rate effect, while Bloom's syndrome cells do not.
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PMID:Response of cells of human origin, normal and malignant, to acute and low dose rate irradiation. 351 54

Ataxia telangiectasia is a genetically determined disease with multi-system abnormalities and a high incidence of neoplasia. In order to define the nature of the association between ataxia telangiectasia and malignancy, we investigated a patient with the disease and heterozygote for the Mediterranean variant of the X-linked marker glucose 6-phosphate dehydrogenase. Enzymatic mosaicism in hemopoietic and nonhemopoietic cells was evaluated with the 2-deoxy glucose 6-phosphate technique. While erythrocytes, platelets, and lymphocytes expressed the same double-enzyme phenotype as tissues of nonhemopoietic origin, granulocytes and monocytes expressed almost exclusively the Mediterranean-type enzyme. We suggest that, as the result of genetic instability at the hemopoietic stem-cell level, the granulocytic/monocytic progeny enjoyed a proliferative advantage and became the predominant clone.
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PMID:A case of ataxia telangiectasia with unbalanced glucose 6-phosphate dehydrogenase mosaicism in the granulocytic/monocytic lineages. 381 85

We reported previously that human cells after neoplastic transformation in culture had acquired an increased susceptibility to chromatid damage induced by x-irradiation during the G2 phase of the cell cycle. Evidence suggested that this results from deficient DNA repair during G2 phase. Cells derived from human tumors also showed enhanced G2-phase chromosomal radiosensitivity. Furthermore, skin fibroblasts from individuals with genetic diseases predisposing to a high risk of cancer, including ataxia-telangiectasia, Bloom syndrome, Fanconi anemia, and xeroderma pigmentosum exhibited enhanced G2-phase chromosomal radiosensitivity. The present study shows that apparently normal skin fibroblasts from individuals with familial cancer--i.e., from families with a history of neoplastic disease--also exhibit enhanced G2-phase chromosomal radiosensitivity. This radiosensitivity appears, therefore, to be associated with both a genetic predisposition to cancer and a malignant neoplastic state. Furthermore, enhanced G2-phase chromosomal radiosensitivity may provide the basis for an assay to detect genetic susceptibility to cancer.
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PMID:Chromosomal radiosensitivity during the G2 cell-cycle period of skin fibroblasts from individuals with familial cancer. 386 Aug 70


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