Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Thorotrast is an alpha-particle-emitting radiological contrast medium that caused chronic exposure to internal alpha-particle radiation when it was administered systemically. Cancer incidence in 432 Swedish patients exposed to Thorotrast was evaluated by computerized linkage of the cohort with the Swedish Cancer Register. Standardized incidence ratios (SIRs) were calculated as the ratio of observed cases in the cohort to expected cases in the general population. A total of 170 cancers occurring in 152 individuals were reported, whereas only 57 cases were expected. The SIR was significantly increased for cancer at all sites (3.0), with the largest excesses noted for primary liver and gallbladder cancer (SIR = 39.2). Other significantly elevated risks were observed for liver cancer not specified as primary, small intestine cancer, stomach cancer, leukemia, kidney cancer, CNS tumors, and pancreatic cancer. Among women, there was a significantly increased risk for lung cancer, based on a small number. Our results show that cumulative radiation exposure is directly related to carcinogenesis in the liver and gallbladder, which is consistent with earlier findings. In addition, there may be a relationship between radiation exposure and the development of other solid tumors.
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PMID:Cancer incidence among Swedish patients exposed to radioactive thorotrast: a forty-year follow-up survey. 1189 44

Trends in mortality rates are usually presented per tumour site or per country without an overall analysis of the complete data encompassing all three aspects (tumour sites, countries, trends). This paper presents a methodology for such an overall analysis using three-way methods applied to a data set on female mortality rates for 17 tumour sites of 43 countries for the years 1968-1985. Multivariate techniques like biplots and three-mode principal component analysis within an overall three-way analysis-of-variance framework were used. We confirmed the known patterns of comparatively high mortality for women due to cancer of the bladder, intestines, pancreas, rectum, breast, ovary, skin and leukaemia and the relatively low mortality rates for liver cancer in Western and Northern Europe, the USA, Australia and New Zealand. Also, the reverse pattern was observed for Middle and Southern Europe, Hong Kong, Singapore, and in Japan, and in some but not all Latin American countries. The relatively mortality due to cancer was high in the lungs, mouth, larynx and oesophagus in the British Isles, but was much less in other European countries. Mortality due to cancer of the thyroid, uterus, gall bladder and stomach was high in Middle European countries, as was the case in Japan, Chile and Costa Rica. Rates were low for Southern European countries, North America, Australia and New Zealand. Specific deviating patterns in the data were the more rapidly decreasing mortality rates for stomach cancer in Chile and Japan and the more rapidly increasing mortality rates for lung cancer in the USA, Scotland and Denmark. In conclusion, using three-way methods, it was feasible to analyse the cancer mortality data in their entirety. This enabled the simultaneous comparison of trends in relative mortality rates between all countries due to all tumour sites, as well as the identification of specific deviating trends for specific tumour sites in specific countries.
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PMID:Added value of three-way methods for the analysis of mortality trends illustrated with worldwide female cancer mortality (1968-1985). 1209 59

Maitake mushroom (Grifola frondosa) MD-fraction containing beta-1,6 glucan with beta-1,3 branched chains has previously exhibited strong anticancer activity by increasing immune-competent cell activity.1,2 In this non-random case series, a combination of MD-fraction and whole maitake powder was investigated to determine its effectiveness for 22- to 57-year-old cancer patients in stages II-IV. Cancer regression or significant symptom improvement was observed in 58.3 percent of liver cancer patients, 68.8 percent of breast cancer patients, and 62.5 percent of lung cancer patients. The trial found a less than 10-20 percent improvement for leukemia, stomach cancer, and brain cancer patients. Furthermore, when maitake was taken in addition to chemotherapy, immune-competent cell activities were enhanced 1.2-1.4 times, compared with chemotherapy alone. Animal studies have supported the use of maitake MD-fraction for cancer.
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PMID:Can maitake MD-fraction aid cancer patients? 1249 70

The subjects for the present study were 270 patients with prostate cancer who underwent initial treatment at our hospital over the 14 years from 1986 to 1999. They were investigated to assess the relationship between their treatment and metachronous tumors. Sixteen patients (5.9%) developed cancer of other organs after starting treatment for prostate cancer. These metachronous tumors included gastric cancer in six patients as well as lung cancer, esophageal cancer, colorectal cancer, liver cancer, renal cancer, bladder cancer, skin cancer, leukemia, and mediastinal adenocarcinoma. Treatment for prostate cancer other than surgery included radiotherapy in eight patients, administration of estramustine phosphate sodium in nine patients, and LH-RH analogues in six patients. The chi-square test showed no significant difference in the incidence of metachronous cancer in relation to the presence/absence of these three therapies. The present study therefore ruled out the possible induction of other tumors by treatment for prostate cancer.
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PMID:[Second cancer after starting treatment for prostate cancer]. 1221 69

Boswellic acids are the compounds isolated from the gum resin of Boswellia serrata and have been used for the treatment of inflammatory diseases for many years in the countries of the east. Recently, a few studies showed that the acids may have anti-cancer effect on leukemia and brain tumours. We investigated the apoptotic and anti-proliferative effects of two types of boswellic acids, keto-beta-boswellic acid and acetyl-keto-beta-boswellic acid, on liver cancer Hep G2 cells. After treating the cells with the boswellic acids, cell proliferation, DNA synthesis, and apoptosis were analysed. The activities of caspase-3, -8 and -9 were assayed. To explore the apoptotic pathway, specific caspase inhibitors were employed. It was found that boswellic acids decreased cell viability and [3H]thymidine incorporation, checked the cells in the G1 phase, and increased percentage of sub-G1. Boswellic acids strongly induced apoptosis accompanied by activation of caspase-3, -8 and -9. The apoptosis was blocked completely by caspase-8 or caspase-3 inhibitor, but inhibited partly by caspase-9 inhibitor. However, these caspase inhibitors did not show any effect on the alternations of cell viability caused by boswellic acids. In conclusion, boswellic acids have anti-proliferation and anti-cancer effects on Hep G2 cells. The apoptotic effect is mediated by a pathway dependent on caspase-8 activation. The acids may be a promising drug for the chemoprevention of liver cancer.
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PMID:Keto- and acetyl-keto-boswellic acids inhibit proliferation and induce apoptosis in Hep G2 cells via a caspase-8 dependent pathway. 1223 1


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