Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aziridinyl substituted cyclophosphazenes are a new group of inorganic chemical agents with in vitro and in vivo cytotoxic activity. We investigated the mode of action on DNA of three different compounds, 1,3,3,5,5-pentakis (1-aziridinyl)-1 lambda 6,2,4,6,3 lambda 5,5 lambda 5-thiatriazadiphosphorine -1-oxide (SOAz), trans-1,3-bis(1-aziridinyl)-1,3,5,5-tetrakis (methylamino)-2,4,6,1 lambda 5,3 lambda 5,5 lambda 5-triazatriphosphorine (AZP), and 1,trans-5-bis(1-azaridinyl)-gem-1,3,3'-cis-5,7,7'-hexakis (methylamino)-2,4,6,8,1 lambda 5,3 lambda 5,5 lambda 5,7 lambda 5 -tetraazatetraphosophocine (AZM), of this group in the Ehrlich ascites tumor cell line (EAT) and a human small cell carcinoma cell line. The DNA damage was evaluated by alkaline elution and ethidium bromide fluorescence assay. Each compound gave a different pattern of DNA damage. SOAz caused neither single strand breaks nor cross-links, AZP gave cross-links, and AZM gave single strand breaks and cross-links in both cell lines after drug incubation for 6 h. The range of concentrations leading to cytoxicity of AZP and AZM in the clonogenic assay coincided with the concentrations leading to DNA damage. Cell kill occurred with SOAz in the same range of concentrations, however, without detectable evidence of DNA damage. It was concluded that cyclophosphazenes are probably a heterogeneous group as far as their mode of action as cytostatic agents is concerned.
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PMID:Different type of DNA damage caused by three aziridinyl substituted cyclophosphazenes in a human small cell lung carcinoma cell line. 300 99

The proliferation activity of adherent, tumor-associated macrophages (TAM) from three related murine mammary carcinoma lines was measured by fluorescence-activated cell sorter (FACS) analysis of the incorporation of 5'-Bromo-2'deoxyuridine (BrdU) in vivo during a 1 hr period prior to tumor removal. The tumor lines examined were line 67 which is nonmetastatic following either subcutaneous (SC) or intravenous (IV) injection, line 168 which colonizes the lung after IV injection but not SC, and line 66 which can colonize the lung from either site. The percentage of total cells identified morphologically as macrophages were similar for tumors from lines 66 and 67 (41% and 38%, respectively), as compared to line 168 tumors, in which, after digestion, 27% of cells were identified as macrophages (P less than or equal to 0.05). Adherent TAM from line 66 tumors had the greatest percentage of BrdU incorporating cells, with an average of 22%. This was statistically significant (P less than or equal to 0.01) from TAM from tumors of line 67, which were 13% positive. The percentage of adherent TAM from line 168 tumors (18% positive) was also significantly different from 67 TAM (P less than or equal to 0.01). These results demonstrate a possible correlation between the percentage of TAM undergoing replication and the ability of the host tumor to colonize the lung. There is no apparent relationship between the percentage of TAM in replication and the number of macrophages associated with a tumor.
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PMID:FACS analysis of tumor-associated macrophage replication: differences between metastatic and nonmetastatic murine mammary tumors. 347 Apr 15

Cultured MGH-U1 (human urinary bladder carcinoma) cells were treated with doxycycline (DOTC) and long-wave UV radiation (UVA). At UVA doses of 1 J/cm2 and above, the cells showed mitochondrial damage, reflected by altered localization of the fluorescent probe rhodamine-123, and striking vacuolization of the cytoplasm. Cell membrane integrity, as monitored by exclusion of ethidium bromide, was maintained for several hours after mitochondrial damage was evident. These changes were potentiated by irradiation in the presence of deuterium oxide, and diminished by irradiation in the presence of sodium azide. Addition of catalase, superoxide dismutase, or mannitol did not alter the damage threshold. These data indicate that the mitochondrion is an earlier target of DOTC photosensitization than the cell membrane. The critical photochemistry appears to involve singlet oxygen.
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PMID:Mitochondrial phototoxicity sensitized by doxycycline in cultured human carcinoma cells. 373 84

Total potassium was assayed in 150 normal weight and obese females (cervical carcinoma-52, endometrial carcinoma-25 and breast cancer-73) by measurements of 40K spontaneous radiation in a low-background chamber. Control group included 30 healthy and 25 obese females. Computations of body cell and extracellular mass and fat were carried out on the basis of the said measurements. Extracellular fluid volume was measured in 38 patients by X-ray fluorescence method using sodium bromide. The results pointed to a body cell mass deficit matched by increased extracellular mass due to a higher fat level in patients with breast, endometrial and cervical carcinoma. The said correlation was particularly pronounced in obese patients. The beneficial effect of treatment was more often observed in patients with normal body weight.
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PMID:[Study of body composition by potassium-40 measurement in patients with breast and uterine cancer]. 373 95

There is continuing concern about the role of irritation in cancer development. Methyl bromide, a widely used fumigant and known irritant reported to cause forestomach carcinomas in rats, was dissolved in peanut oil and given by gavage at 50 mg/kg body wt to Wistar rats five times per week for 13 to 25 weeks. Starting at Week 13, methyl bromide administration was discontinued for half of the methyl bromide-treated rats (stop treatment group). After that, rats from both the continuous treatment and stop treatment groups were terminated at 4-week intervals to follow the progression of the stomach lesions. Forestomach lesions were not found in control rats receiving peanut oil and killed at 13 or 25 weeks. At 13 weeks the forestomachs from rats receiving methyl bromide were contracted and adherent to the liver and spleen. Inflammation, acanthosis, fibrosis, and a high incidence of pseudoepitheliomatous hyperplasia were found microscopically in treated animals. At 25 weeks, 100% of the rats receiving methyl bromide continuously had hyperplastic lesions of the forestomach which were more severe than those at 13 weeks. Evidence of malignancy was seen in one rat and the lesion was considered a very early carcinoma. In the stop treatment group that received methyl bromide for 13 weeks, there was regression of the stomach lesions, but at the 12-week final sacrifice, adhesions, fibrosis, and mild acanthosis remained. This study illustrates the need for regression experiments for complex forestomach lesions in rodents, especially when an irritating chemical is given by gavage.
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PMID:Regression of methyl bromide-induced forestomach lesions in the rat. 376 33

The DNase I digestion kinetics of DNA in isolated nuclei (from HeLa or murine mammary carcinoma, 67 cells) were assayed flow cytometrically by measuring the changes in ethidium bromide (EtBr) fluorescence following various digestion time intervals. The DNase I digestion curve was characterized by an initial 25-30% increase in fluorescence upon addition of the enzyme, a rapid reduction in fluorescence to approximately 50-55% in 30 minutes, and a limit digest of 45-50% beyond 45 minutes. Throughout digestion, the DNA histogram retained its characteristic bimodal shape, showing that histogram rearrangement was not responsible for the changes in EtBr fluorescence. Irradiation with 5 X 10(6) rads (137Cs-gamma-rays) or exposure to 50 mM EDTA caused an increase in EtBr fluorescence similar to that caused by DNase I, suggesting that DNA nicking and/or chromatin loosening were responsible for this increase. Residual DNA assayed by the solubilization of 14C-TdR (thymidine)-labeled DNA indicated a similar kinetic pattern without the initial increase. However, at the limit digest, the fraction of DNA remaining trichloroacetic acid (TCA) insoluble (10%) was smaller than that measured by loss of EtBr fluorescence (50% of initial, 40% of maximum). Part of this difference was due to the presence of TCA soluble DNA trapped within the nuclear matrix (15-20%). This trapped DNA was released when the digested nuclei were exposed to 0.5-1.0 M NaCl just prior to EtBr staining. Exposure of HeLa cells to three agents that are believed to cause changes in chromatin structure resulted in alterations in the DNase I digestion kinetics measured flow cytometrically.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:DNase I sensitivity of nuclear DNA measured by flow cytometry. 397 14

The tritium-labelled acyclonucleoside, N-[2-(hydroxyethoxy)methyl]-5-[3H]methyluracil (3H-3), was synthesized for evaluation as a tumor diagnostic agent. 5-[3H]-Methyluracil, 3H-1, was converted to the 2,4-bis-trimethylsilyl intermediate which was coupled with 2-acetoxyethoxymethyl bromide to afford 1-[(2-acetoxyethoxy)methyl-5-[3H]methyluracil (3H-2). Treatment of 3H-2 with sodium methoxide in methanol afforded 3H-3 (specific activity 188 MBq mmol-1. The tissue distribution of 3H-3 was examined in male BDF1 mice bearing Lewis Lung (LL) carcinomas. Long bone exhibited the highest tumor: tissue ratios. The kidney contained the highest radioactivity level relative to the tumor. This suggested a major urinary route of excretion. The major radioactive blood component (89.21%) was found to have a biological half-life of 0.19 min. The title compound is unsuitable for use as a diagnostic agent for LL carcinoma because of low tumor uptake and rapid urinary elimination of injected radioactivity from the body.
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PMID:Tumor uptake of radiolabelled pyrimidine bases and pyrimidine nucleosides in animal models--VIII. Synthesis and tissue distribution of N-[2-(hydroxyethoxy) methyl]-5-[3H]methyluracil. 401

Electron immunohistochemical studies demonstrate that cultured embryo-derived parietal yolk sac (ED-PYS) carcinoma cells synthesize type IV collagen. This material has been isolated and characterized. The collagen obtained after limited pepsin digestion from the medium in which the cells are grown is composed of homogeneous components with a molecular mass of approximately 95 000 daltons. When chromatographed on (carboxymethyl)cellulose under denaturing conditions, the chains elute as acidic components slightly before the human alpha 1(I) chain and coincident with the position of elution of the pepsin-derived human alpha 1(IV) chain. This analysis indicates the presence of a single type of collagen chain in the pepsin-derived ED-PYS synthesized material. In addition, the profile of cyanogen bromide (CNBr) cleavage products obtained from the pepsin-derived ED-PYS cell collagen chains is essentially identical with that derived from the human alpha 1(IV) chain. Isolation of the medium collagen in the absence of pepsin digestion reveals the presence of two high molecular weight components equivalent in size to procollagen alpha chains. However, both high molecular weight products yield CNBr cleavage products that correspond to those obtained from the pepsin-derived alpha 1(IV) chain. The ED-PYS cell-associated collagens obtained with or without the use of pepsin contain components that are essentially identical with those isolated from the culture-medium collagen. These data provide definitive evidence for the existence of type IV collagen molecules composed solely of alpha 1(IV) procollagen chains and further document the usefulness of ED-PYS cells for investigating the biosynthesis of basement membrane components.
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PMID:Synthesis of [pro alpha 1(IV)]3 collagen molecules by cultured embryo-derived parietal yolk sac cells. 408 92

2 cases of acanthosis nigricans associated with an adenocarcinoma (signet ring cell carcinoma) of the stomach and a metastasizing small-cell carcinoma of unknown origin are reported. In both cases the skin lesions preceded the diagnosis of the carcinoma by months and acanthosis nigricans maligna was suspected by onset and localization of the dermatosis. There was no evidence of a papillomavirus etiology of the warty skin lesions. Virus particles could not be demonstrated either in ultrathin sections or in buffer extracts. Virus-specific DNA was not detectable after CsCL-ethidium bromide gradient centrifugation and cellular DNA did not hybridize under stringent or relaxed conditions with 32P-labelled human papillomavirus 6 or human papillomavirus 8 DNA.
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PMID:Acanthosis nigricans maligna. Clinical and virological investigations. 608 13

The primary structures of three polypeptides, possessing high intrinsic growth hormone-releasing activity and derived from a human pancreatic carcinoma which had caused acromegaly, were established by sequence analyses of the intact peptides and their cyanogen bromide digestion fragments with a gas-phase sequenator. The three human pancreas growth hormone-releasing factors contain 44 (hpGRF-44), 40 (hpGRF-40), and 37 (hpGRF-37) amino acids in identical sequences from their NH2 termini. High pressure liquid chromatography of the native peptides and their synthetic replicates showed that hpGRF-37 and hpGRF-40 possess free carboxyl termini while that of hpGRF-44 is amidated. The structure of hpGRF-44 was established as: Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-Gln-Gln-Gly-Glu-Ser-Asn-Gln-Glu-Arg-Gly Ala-Arg-Ala-Arg-Leu-NH2.
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PMID:Primary structures of three human pancreas peptides with growth hormone-releasing activity. 613 96


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