UMLS:C0023418 - FACTA Search

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Query: UMLS:C0023418 (leukemia)
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The 150 male patients exposed to Thorotrast who were confirmed by a 1975-1978 national survey with diagnostic X rays of 50,860 war-wounded soldiers were followed up between 1979 and 1998 (Aichi series or second series). Age-adjusted rate ratios of deaths from all causes were 3.0 times higher in Thorotrast patients compared to controls; this was statistically significant. Rate ratios for liver cancer, liver cirrhosis and leukemia were 35.0, 7.5 and 18.2, respectively.
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PMID:Cancer mortality of thorotrast patients in Japan: the second series updated 1998. 1056 42

Updated data from two series in a cancer mortality study for a total of 412 Japanese Thorotrast patients were combined. The rate ratio for all deaths of Thorotrast patients, compared to controls, started to increase after a latent period of 20 years after injection of Thorotrast. Rate ratios for liver cancer, liver cirrhosis, leukemia and lung cancer were 35.9, 6.9, 12.5 and 2.0 times higher, respectively, than those for controls.
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PMID:Summary of entire Japanese thorotrast follow-up study: updated 1998. 1056 43

The Portuguese Thorotrast study cohort consists of a group of patients who received Thorotrast for diagnostic reasons between 1929 and 1956, and a group of similar patients who were given nonradioactive contrast agents. The cohort members were identified from medical records that contained information on reasons for the radiological investigation, type of procedure employed, and name and dose of the contrast medium used. This cohort was assembled in 1961, but its follow-up was interrupted in 1976. We have now reactivated this cohort and extended its follow-up through the end of 1996. Similar methods were used to follow up and ascertain cause of death for the Thorotrast-exposed and unexposed subjects. A total of 1931 patients who received Thorotrast systemically and 2258 unexposed subjects were initially identified from medical records. We were able to successfully follow up 58.6% (1131) of the Thorotrast patients and 45.7% (1032) of the unexposed patients. By the end of 1996, 92.2% of the Thorotrast patients and 75.2% of the unexposed patients were dead. Mortality from all causes was increased in the Thorotrast patients compared to those who were not exposed. This excess in mortality increased with time since exposure, peaking 30 years after administration of Thorotrast. The rise in overall mortality was essentially due to neoplasms [relative risk (RR) adjusted for sex, age and period = 6.04, 95% CI = 4.42-8.26], nonmalignant liver disorders (RR = 5.67, 95% CI 3.13-10.3) and nonmalignant hematological conditions (RR = 14.2, 95% CI = 2.54-79.3). The increase in mortality from neoplasms was explained mainly by increases in the risk of liver cancer (RR = 70.8, 95% CI = 19.9-251.3) and, to a much lesser extent, leukemia (RR = 15.2, 95% CI = 1. 28-181.7).
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PMID:Mortality in the Portuguese thorotrast study. 1056 44

Vinyl chloride (VC) is both a known carcinogen and a regulated chemical, and its production capacity has almost doubled over the last 20 years, currently 27 million tons/year worldwide. According to recent reports it is still a cause for concern. VC has been found as a degradation product of chloroethylene solvents (perchloroethylene and trichloroethylene) and in landfill gas and groundwater at concentrations up to 200 mg/m(3) and 10 mg/L, respectively. Worldwide occupational exposure to VC still seems to be high in some countries (e.g., averages of approximately 1,300 mg/m(3) until 1987 in one factory), and exposure may also be high in others where VC is not regulated. By combining the most relevant epidemiologic studies from several countries, we observed a 5-fold excess of liver cancer, primarily because of a 45-fold excess risk from angiosarcoma of the liver (ASL). The number of ASL cases reported up to the end of 1998 was 197 worldwide. The average latency for ASL is 22 years. Some studies show a small excess risk for hepatocellular carcinoma, and others suggest a possible risk of brain tumors among highly exposed workers. Lung cancer, lymphomas, or leukemia do not seem to be related to VC exposure according to recent results. The mutation spectra observed in rat and human liver tumors (ASL and/or hepatocellular carcinoma) that are associated with exposure to VC are clearly distinct from those observed in sporadic liver tumors or hepatic tumors that are associated with other exposures. In rats, the substitution mutations found at A:T base pairs in the ras and p53 genes are consistent with the promutagenic properties of the DNA adduct 1,N(6)-ethenoadenine formed from VC metabolites. Risk assessments derived from animal studies seem to overestimate the actual risk of cancer when comparing estimated and reported cases of ASL.
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PMID:Vinyl chloride: still a cause for concern. 1090 93

Cycloprodigiosin hydrochloride (cPrG * HCl), a novel H(+)/Cl(-) symporter, induces acidification of the cytosol and leads to apoptosis in rat and human liver cancer cells. In the present study, the effect of cPrG * HCl on a promyelocytic leukemia cell line (HL-60) was examined. cPrG * HCl lowered intracellular pH and induced apoptosis through up-regulation of Fas ligand, activation of stress-activated protein kinase (SAPK/JNK) and caspase. Apoptosis induced by cPrG * HCl was strongly suppressed when a cell-permeable weak base, imidazole, was present, indicating that cytosol acidification introduced by cPrG * HCl triggered caspase activation, leading to apoptosis. Concomitantly, cell differentiation into monocyte was also induced by cPrG * HCl both morphologically and functionally. However, the cPrG * HCl-induced differentiation was not suppressed by addition of imidazole, indicating that the differentiation process is unrelated to cytosol acidification. Further, the differentiation induced by cPrG * HCl was blocked by tyrosine kinase inhibitors (lavendustin A and HMA) but unaffected by the inhibitors of A-kinase (H-89) or C-kinase (H-7). Taken together, these findings suggest that cPrG * HCl, through apoptosis and differentiation induction, may be useful in leukemia treatment.
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PMID:Cycloprodigiosin hydrochloride, H(+)/CL(-) symporter, induces apoptosis and differentiation in HL-60 cells. 1096 49

1,3-Butadiene, isoprene and chloroprene have all been evaluated more than once by the IARC Monographs Programme on the Evaluation of Carcinogenic Risks to Humans, most recently in February 1998 (Volume 71). Summaries are available on-line at http://monographs.iarc.fr. 1,3-Butadiene is currently classified in Group 2A (probably carcinogenic to humans), on the basis of limited evidence for increased occupational cancer risk in humans plus sufficient evidence of carcinogenicity at multiple organ sites in rats and especially in mice exposed by inhalation. Four epidemiologic studies are available on cancer risk among workers exposed to 1,3-butadiene, one large study among styrene-butadiene rubber (SBR) workers, and one large and two small studies among 1,3-butadiene production workers. The results of the study of SBR workers suggest an association between butadiene exposure and leukaemia risk, which is consistent with the results of the large study of production workers. This latter study also suggested an increased risk of lymphoreticulosarcoma (ICD-8, 200). The major factors hampering the assessment of the available results are (i) possible misclassification of lymphoid and haematopoietic neoplasms, (ii) limitations in the assessment of past exposure (with the exception of the study of SBR workers) and (iii) a potential confounding effect of agents other than butadiene. Future research priorities include (i) the incorporation of newly developed biomarkers of exposure, (ii) the possible application of intermediate biomarkers, (iii) the replication of the study among SBR workers, possibly in Europe, and (iv) reanalysis of existing data in light of revisions of the classifications of leukaemias and lymphomas in the International Classification of Diseases for Oncology, Third Edition (2000). Isoprene is classified in Group 2B (possibly carcinogenic to humans), on the basis of sufficient evidence for carcinogenicity at multiple organ sites in both mice and rats, especially male mice, exposed by inhalation. No epidemiologic studies are available on cancer risk from occupational exposure to isoprene. Such studies could be conducted within the framework of existing or future studies of SBR workers, assuming that isoprene exposure can be disentangled from butadiene and styrene exposure. Chloroprene is classified in Group 2B on the basis of sufficient evidence for carcinogenicity at multiple organ sites in both mice and rats exposed by inhalation. Studies of chloroprene exposed workers now include chemical workers from the United States, China and Armenia as well as shoe workers from Russia. The results of the studies from China, Armenia and Russia suggest an excess risk of liver cancer. The risk of other neoplasms was not consistently increased. Limitations of available studies include possible bias from cohort enumeration, follow-up, and choice of reference population. In most studies the exposure assessment was poor, the possible confounding effect of co-exposures was not addressed and the statistical power was low. The pathology of the cases of liver cancer should be reviewed. Future research priorities include a replication of available studies in well-defined populations and the development of biomarkers of exposure.
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PMID:1,3-Butadiene, isoprene and chloroprene: reviews by the IARC monographs programme, outstanding issues, and research priorities in epidemiology. 1139 78

Two retrospective cohort studies were conducted to assess the risk of cancer among workers exposed to chloroprene (2-chloro-1,3-butadiene) (CP). One is a study of incidence and mortality among 2314 production workers employed in the CP production plant in Yerevan, Armenia, between 1940 and 1988. The cohort was followed up for cancer incidence for the years 1979-1990 and for cancer mortality for 1979-1988. The second study is a mortality study among 5185 shoe manufacturing workers in Moscow who used polychloroprene latex and glue. Shoe workers were employed between 1940 and 1976, and followed from 1979 through 1993. The standardized incidence ratios (SIR) and standardized mortality ratios (SMR) were calculated using the Armenian and Moscow population as reference. An internal comparison analysis based on Poisson regression modeling was conducted. In the Yerenan cohort, incidence and mortality from all cancers were below expectation, but increased incidence (SIR, 3.27; 95% confidence interval (CI), 1.47-7.27), and mortality (SMR, 3.39; CI, 1.09-10.5) from liver cancer were noted. A dose-response relationship was suggested between the risk of liver cancer and indices of CP exposure. For the entire Moscow cohort, all-cause mortality was close to expectation and all-cancer mortality was increased. There was an increase in the mortality from liver cancer (SMR, 2.4; CI, 1.1-4.3), kidney cancer (SMR, 1.8; CI, 0.9-3.4), and leukemia (SMR, 1.9; CI, 1.0-3.3). Mortality from liver cancer and leukemia was associated with various indicators of CP exposure. A similar, although less consistent, pattern was found for kidney cancer. The association between CP exposure and risk of leukemia may be due to concomitant exposure to benzene. The results for liver cancer point towards a carcinogenic effect of CP.
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PMID:Cohort studies of chloroprene-exposed workers in Russia. 1139 8

Epidemiological studies have suggested that ataxia-telangiectasia (AT) heterozygotes have a predisposition to cancer, especially breast cancer in women. Now, haplotyping can identify heterozygotes for AT mutation (ATM) in AT families, allowing the risk of cancer associated with ATM heterozygosity status to be better assessed. We report a family study of AT patients, in which we estimated the risk of cancer according to ATM heterozygosity status. We analyzed demographic characteristics and occurrence of cancer in 1,423 relatives of AT patients. Haplotyping was performed in living relatives. The probability of being heterozygotes for ATM was calculated for deceased relatives. The risk of developing cancer was estimated in the cohort of relatives, and expected numbers of cancer cases were calculated from French age period-specific incidence rates. The number of cancers at all sites in the total population of relatives was not higher than expected. However, significant heterogeneity was found according to ATM heterozygosity status. This is mainly due to the increased risk of breast cancer previously observed in obligate heterozygotes. In obligate heterozygotes, relative risk (RR) was non-significantly increased for thyroid cancer, leukemia and liver cancer. Risks of ovarian, lung, pancreatic, kidney, stomach and colorectal cancers were non-significantly increased in the group with 0.5 probability of being heterozygotes. The RR was not significantly increased for any site of cancer, except for breast. Therefore, there is no evidence that specific screening of relatives of AT patients would be justified at particular sites other than the breast. However, the amplitude of the risk of breast cancer estimated in heterozygous women does not appear to justify a separate screening program from that already available to women with a first-degree relative affected by breast cancer.
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PMID:Cancer risk in heterozygotes for ataxia-telangiectasia. 1141 Aug 79

We studied the alpha-radiation risks in patients who received injections of Thorotrast, an X-ray contrast medium used in Europe, Japan, and the United States from 1930 to 1955. Thorotrast was composed of thorium dioxide (ThO2) and Th-232, a naturally occurring radionuclide. Because the physical half-life of ThO2 is 14 billion years and Thorotrast is hardly eliminated from the body, tissues in which it was deposited are irradiated by alpha-radiation for the entire lifetime of the subject. The dosimetry of Thorotrast patients is very complicated, but currently its reliability is quite high compared with other irradiated populations. The major causes of the death of Thorotrast patients are liver cancer, liver cirrhosis, leukemia, and other cancers. Three histologies of liver cancer are found: cholangiocarcinoma, hepatocellular carcinoma, and angiosarcoma. Although cholangiocarcinoma is the most frequent, angiosarcoma is characteristic of alpha-radiation. Among blood neoplasms with a higher incidence of increase than the general population, erythroleukemia and myelodysplastic syndrome were remarkable. Thorotrast patients exhaled a high concentration of radon (Rn-220), a progeny of Th-232, but no excesses of lung cancer in the patients of Japan, Germany, and Denmark were reported. Mutation analyses of p53 genes and loss of heterozygosity (LOH) studies at 17p locus were performed to characterize the genetic changes in Thorotrast-induced liver tumors. Interestingly, LOH, supposedly corresponding to large deletions was not frequent; most mutations were transitions, also seen in tumors of the general population, suggesting that genetic changes of Thorotrast-induced cancers are mainly delayed mutations, and not the result of the direct effects of radiation.
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PMID:Alpha-particle carcinogenesis in Thorotrast patients: epidemiology, dosimetry, pathology, and molecular analysis. 1179 40

We have designed and synthesized new 5-lipoxygenase inhibitors, fluorinated 3,4-dihydroxychalcones, and evaluated their biological activities with respect to antiperoxidation activity and in vitro antitumor activities. All fluorinated chalcones tested showed 5-lipoxygenase inhibition on rat basophilic leukemia-1 (RBL-1) cells and inhibitory action on Fe(3+)-ADP induced NADPH-dependent lipid peroxidation in rat liver microsomes. The potencies were comparable or better to that of the lead 3,4-dihydroxychalcone. 6-Fluoro-3,4-dihydroxy-2',4'-dimethoxy chalcone (7) was the most effective compound in the in vitro assay using a human cancer cell line panel (HCC panel) consisting of 39 systems.
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PMID:Synthesis and biological activities of fluorinated chalcone derivatives. 1181 58

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