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

Recently, Volk, Geiger, and Raz (Cancer Res., 44: 811-824, 1984) addressed the question of whether variations in actin organization in clones of the murine K-1735 melanoma tumor correlated with their metastatic capability. Using immunofluorescence techniques, they found that clones which had a more ordered actin network were less metastatic, whereas clones having a diffuse actin staining pattern were more metastatic. Similarly, we have found that in the Dunning rat R3327 prostatic adenocarcinoma tumor system, the non-metastatic (less than 0.1%) H-prostatic tumor cell line has a prominent network of actin filament bundles, whereas the highly metastatic (greater than 90%) MatLyLu cell line has a diffuse actin staining pattern. In the low-metastatic (less than 10%) AT1 cell line an intermediate actin organization between H and MatLyLu was observed. Analysis of cell extracts from H- and MatLyLu-cells revealed differences in the level of activity of cellular proteins which affect actin filament assembly and structure in a manner similar to that of the cytochalasins, fungal metabolites which bind with high affinity to the fast-growing end of actin filaments. Extracts of MatLyLu were significantly more effective than those of H-cells in decreasing the extent of actin filament network formation and in inhibiting the rate of filament assembly by blocking monomer addition onto the fast-growing end. Measurements of spin-lattice nuclear magnetic resonance water proton relaxation times (T1) were made in surgically removed tumor tissue from four sublines (H, AT1, MatLyLu, and MatLu) of the Dunning R3327 tumor system. The highly metastatic cell lines had significantly longer water proton T1 relaxation times than did the lines with low metastatic potential. These differences in T1 may reflect the observed alterations in organization of actin filaments within these various sublines of the Dunning R3327 prostatic adenocarcinoma tumor system.
 ...
PMID:Actin filament organization of the Dunning R3327 rat prostatic adenocarcinoma system: correlation with metastatic potential. 394 Jun 53

Fibroblast strains from 6 patients with ataxia telangiectasia (A-T) were found to be markedly hypersensitive to the cytotoxic action of the tumor promoter phorbol-12-myristate-13-acetate (PMA), their D37 values being 5 times lower than those of two normal controls. Two A-T heterozygous strains were slightly hypersensitive to PMA, while a third one showed normal sensitivity. It is concluded that the DNA lesion which is critical in A-T cells is an important component of the damage caused by PMA-induced free radicals and may play a role both in the tumor-promoting activity of PMA and the cancer proneness of A-T patients.
 ...
PMID:Cells from patients with ataxia telangiectasia are abnormally sensitive to the cytotoxic effect of a tumor promoter, phorbol-12-myristate-13-acetate. 398 47

Skin fibroblasts were cultured from 15 patients with primary immunodeficiency diseases associated with a high cancer risk, including sex-linked agammaglobulinemia, IgA deficiency, variable immunodeficiency, ataxia-telangiectasia (cerebellar malfunction and abnormalities of blood vessels and immune response), Wiskott-Aldrich syndrome (low platelet count, eczema, and abnormal immune mechanism), and severe combined system (cellular and humoral) immunodeficiency. Fourteen of 15 cell strains were found to have low or regular susceptibility to transformation with the tumor virus, simian virus 40. The data are consistent with the view that the frequent occurrence of malignancy in patients with primary immunodeficiency is due to abnormalities of the immunologic surveillance mechanism.
 ...
PMID:Susceptibility of cells from patients with primary immunodeficiency diseases to transformation by simian virus 40. 411 42

This paper reports the occurrence of renal cell carcinoma, hepatoma and malignant hepatic mixed tumor in a 22-year-old male with ataxia-telangiectasia (AT). Incidence of various malignant neoplasms is high in the patients with AT. The majority of these are lymphoreticular tumors and leukemia, and epithelial tumors are rare. This report is the first case with renal cell carcinoma and the second with hepatoma. The reason for a low incidence of epithelial tumors in AT is still obscure. It is possible that as the result of abnormal aging the tumors expected in the aged will occur in longer survivors with AT.
 ...
PMID:Ataxia-telangiectasia with renal cell carcinoma and hepatoma. 625 35

The dysplastic nevus syndrome (DNS) is a preneoplastic melanocyte abnormality which occurs in families affected by hereditary cutaneous malignant melanoma (HCMM). A putative role of host-environmental interactions in the etiology of hereditary melanoma has been strengthened by the recent finding that fibroblasts derived from HCMM/DNS patients demonstrated enhanced sensitivity to u.v.-irradiation in vitro. We report here an extension of these studies in which we have examined the in vitro responses to a model environmental carcinogen, 4-nitroquinoline 1-oxide (4NQO), of six non-tumor skin fibroblast strains from HCMM/DNS patients representing five families. Three of the six HCMM/DNS strains showed enhanced cell killing with sensitivities greater than that of a xeroderma pigmentosum (XP) variant strain but less than those of ataxia telangiectasia and XP Group D cell strains. The inhibition and recovery of de novo DNA synthesis, together with the expression of repair synthesis, following 4NQO exposure appeared to be normal in HCMM/DNS strains, irrespective of their subsequent clonogenic potential. Our data point to a metabolic anomaly which may contribute to the carcinogenic risk of the melanoma prone preneoplastic state presented by some DNS patients.
 ...
PMID:Abnormal responses to the carcinogen 4-nitroquinoline 1-oxide of cultured fibroblasts from patients with dysplastic nevus syndrome and hereditary cutaneous malignant melanoma. 640 40

The in vitro production of interferon-alpha and -gamma (IFN) by peripheral blood mononuclear cells from four patients with ataxia-telangiectasia was compared to that of healthy controls. Normal values of IFN-alpha were obtained in all cases. However, patients with ataxia-telangiectasia showed a great reduction or absence of IFN-gamma production after induction with either staphylococcal enterotoxin B or galactose oxidase. This defect was accompanied by the absence of secretion of another lymphokine, namely, interleukin 2 (IL-2), in one case. Lymphoproliferative response to phytohemagglutinin (PHA) was severely depressed in all patients. Near normal values of T lymphocytes were found, but the ratio of OKT4+/OKT8+ subsets was reduced in most patients, due to a decrease of OKT4+ lymphocytes. Deficiency of IFN-gamma may contribute to the abnormalities of immune functions and immunoregulation observed in ataxia-telangiectasia, and it may represent an additional cause of the high incidence of viral infections and neoplasia in this disease.
 ...
PMID:Defective interferon-gamma production in ataxia-telangiectasia. 643 89

A defect in DNA repair coupled to anomalous DNA synthesis after induction of certain radiogenic DNA damage is suspected to underlie the radiosensitivity of cells from patients with ataxia-telangiectasia (A-T). The response of cultured skin fibroblasts from A-T patients and A-T heterozygotes to six agents inducing various levels of DNA strand breakage by different mechanisms was studied to obtain further information on the nature of the 'A-T critical DNA lesion'. The A-T cells showed varying degrees of hypersensitivity to the cytotoxic action of the quinone-containing anti-tumor antibiotics streptonigrin and adriamycin and to hydrogen peroxide. This hypersensitivity was accompanied by reduced inhibition of DNA synthesis compared to normal cells after treatment with these agents. A limited degree of cellular hypersensitivity that was not sufficient to allow for definition of a separate sensitivity range was shown by A-T heterozygous cells. On the other hand, the A-T cells showed a normal response to paraquat, saframycin A and ellipticine. Taken together with previous results showing hypersensitivity of A-T cells to ionizing radiation, bleomycin and neocarzinostatin, these data indicate that the critical DNA lesion in A-T cells is a strand break caused by deoxyribose destruction following the action of free radicals targeted into the DNA.
 ...
PMID:Abnormal response of ataxia-telangiectasia cells to agents that break the deoxyribose moiety of DNA via a targeted free radical mechanism. 661 60

Organ cultures of chick and rabbit embryonic skin were used to assess the tumorigenicity of cultured human cell lines. Cell lines were from patients with (1) specific chromosomal abnormalities and an increased risk of cancer (Down's syndrome, Klinefelter's syndrome, Partial D Trisomy, Bloom's syndrome, Franconi's anemia, ataxia telangiectasia and xeroderma pigmentosum); (2) a specific chromosomal abnormality but no increased risk for cancer (Cri du chat), and (3) a biochemical defect (galactosemia). In addition, tumor cell lines and cell lines of normal origin were used as positive and negative standards. Mitotic ability was quantified by dividing the total number of mitoses in the cell inoculum seen in histologic sections by the number of sections examined to give a computed mean number of mitoses per section (MMS). Neoplastic cell lines showed MMS values greater than 1.0 while cell lines of normal origin were less than 0.25. The cell lines derived from patients with chromosomal abnormalities and the patient with a biochemical defect, whether the individuals were at an increased risk for cancer or not, gave the same range of MMS values as obtained for cells of normal origin. These results that chromosomal aberrations per se do not enhance the cell's capability for proliferation on a xenogenic substrate.
 ...
PMID:Tumorigenicity of chromosomally abnormal human cultured cells in two xenogenic organ culture assays. 720 52

It has been reported that the p53 gene mediates an ionizing radiation-induced G1 arrest in mammalian cells. To further characterize this important phenomenon, a panel of seven human diploid fibroblast cell strains and 14 human tumor cell lines from a variety of sources with both wild-type and mutant p53 status were assayed for their susceptibility to G1 arrest after gamma-ray irradiation by a continuous labeling [3H]thymidine incorporation technique. An irreversible G1-block involving 20-70% of the cell population was observed in diploid fibroblasts irradiated with 4 Gy. The block was abolished by transfection with the Human Papilloma Virus E6 gene and in an ataxia telangiectasia (AT) cell line, indicating a role for the AT and p53 genes respectively in this process. In contrast to wild-type normal fibroblast cell strains, the G1-block in all tumor cell lines was significantly reduced, irrespective of their p53 status. None of the nine human tumor cell lines with mutant p53 genes showed a significant G1-block following irradiation with 4 Gy. Among the five tumor cell lines expressing wild-type p53, two showed no apparent G1-block. The remaining three showed a G1-block involving only 8-15% of the cell population, a block much smaller in magnitude than that seen in diploid fibroblasts. Finally, a diploid fibroblast cell strain and a tumor cell line, both showing a normal p53 and p21/WAF1 expression pattern, were examined for pRb phosphorylation before and after irradiation. The diploid fibroblast cell strain showed a significant G1-arrest and a clear inhibition of pRb phosphorylation by irradiation whereas the tumor cells showed no G1-arrest and no inhibition of pRb phosphorylation. These results suggest that (1) multiple genetic factors may modulate the occurrence and magnitude of the G1-arrest induced by exposure to ionizing radiation, (2) the capacity for p53 to mediate a radiation-induced G1 arrest is significantly reduced in tumor cells, (3) the disruption of G1-block modulating factor(s) other than p53 may be an important step in carcinogenesis.
 ...
PMID:Diminished capacity for p53 in mediating a radiation-induced G1 arrest in established human tumor cell lines. 747 18

Within months of Roentgen's discovery of X rays, severe adverse effects were reported, but not well publicized. As a result, over the next two decades, fluoroscope operators suffered lethal skin carcinomas. Later, case reports appeared concerning leukemia in radiation workers, and infants born with severe mental retardation after their mothers had been given pelvic radiotherapy early in pregnancy. Fluoroscopy and radiotherapy for benign disorders continued to be used with abandon until authoritative reports were published on the adverse effects of ionizing radiation by the U.S. NAS-NRC and the UK MRC in 1956. Meanwhile, exposure to the atomic bombs in Japan had occurred and epidemics of delayed effects began to be recognized among the survivors: cataracts (1949), leukemia (1952) and severe mental retardation among newborn infants after intrauterine exposure (1952). No statistically significant excess of germ-cell genetic effects was detected by six clinical measurements (1956), the F1 mortality (1981), cytogenetic studies (1987) or biochemical genetic studies (1988). Somatic cell effects were revealed by long-lasting chromosomal aberrations in peripheral lymphocytes (1968), and somatic cell mutations were found at the glycophorin A locus in erythrocytes (1992). Molecular biology is a likely focus of new studies based on the function of the gene for ataxia telangiectasia (1995), a disorder in which children have severe, even lethal acute radiation reactions when given conventional doses of radiotherapy for lymphoma, to which they are prone. Also, obligate heterozygote female relatives can be studied for increased susceptibility to radiation-induced breast cancer, as suggested by clinical studies. The tumor registries in Hiroshima and Nagasaki now provide incidence data that show the extent of increases in eight common cancers and no increase in eight others (1994). The possibility of very late effects of A-bomb exposure is suggested by recent reports of increased frequencies of hyperparathyroidism, parathyroid cancers and certain causes of death other than cancer.
 ...
PMID:Delayed effects of external radiation exposure: a brief history. 748 Jun 42


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>