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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The per-capita intakes of zinc, cadmium, copper and of chromium were estimated from food consumption data in 28 countries and were found to correlate directly with the age-corrected mortalities from cancers of intestine, prostate, breast, leukemia, skin and of other organs, suggesting that the anticarcinogenic effect of selenium is counteracted by other trace elements. Similarly calculated dietary intakes of manganese are inversely correlated, particularly with the mortalities from cancer of pancreas, an organ normally known to contain high concentrations of this element. Arsenic intakes correlate inversely with the male lung cancer mortalities. A number of other direct and inverse associations were observed which suggest that trace elements in the human diet may hav both benign and adverse effects on tumor development. The zinc concentrations in whole blood collected from healthy donors in the U.S. correlate directly with regional mortalities from cancers of intestine, breast and of other sites. The origin of these associations is discussed primarily in terms of the seleium-antagonistic effect of zinc and of some of the other elements considered. Results of animal experiments and of other studies are cited which support hypotheses that link human cancer development to possible deficiencies or excesses in the dietary trace element intakes.
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PMID:Cancer mortality correlation studies--IV: associations with dietary intakes and blood levels of certain trace elements, notably Se-antagonists. 85 92

Age-adjusted mortality rates were analyzed to examine the dose-response relation between ingested arsenic levels and risk of cancers and vascular diseases among residents in the endemic area of blackfoot disease, a unique peripheral vascular disease associated with long-term exposure to high-arsenic artesian well water and confined to the southwestern coast of Taiwan. The arsenic levels in well water determined in 1964-1966 were available in 42 villages of the study area, while mortality and population data during 1973-1986 were obtained from the local household registration offices and Taiwan Provincial Department of Health. Age-adjusted mortality rates from various cancers and vascular diseases by sex were calculated using the 1976 world population as the standard population. A significant dose-response relation was observed between arsenic levels in well water and cancers of the bladder, kidney, skin, and lung in both males and females, and cancers of the prostate and liver in males. However, there was no association for cancers of the nasopharynx, esophagus, stomach, colon, and uterine cervix, and for leukemia. Arsenic levels in well water were also associated with peripheral vascular diseases and cardiovascular diseases in a dose-response pattern, but not with cerebrovascular accidents. The dual effect of arsenic on carcinogenesis and arteriosclerosis and the interrelation between these two pathogenic mechanisms deserve more intensive study.
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PMID:Dose-response relation between arsenic concentration in well water and mortality from cancers and vascular diseases. 258 5

PML nuclear bodies (NBs) are nuclear matrix-associated structures altered by viruses and oncogenes. We show here that PML overexpression induces rapid cell death, independent of de novo transcription and cell cycling. PML death involves cytoplasmic features of apoptosis in the absence of caspase-3 activation, and caspase inhibitors such as zVAD accelerate PML death. zVAD also accelerates interferon (IFN)-induced death, suggesting that PML contributes to IFN-induced apoptosis. The death effector BAX and the cdk inhibitor p27KIP1 are novel NB-associated proteins recruited by PML to these nuclear domains, whereas the acute promyelocytic leukaemia (APL) PML/RAR alpha oncoprotein delocalizes them. Arsenic enhances targeting of PML, BAX and p27KIP1 to NBs and synergizes with PML and IFN to induce cell death. Thus, cell death susceptibility correlates with NB recruitment of NB proteins. These findings reveal a novel cell death pathway that neither requires nor induces caspase-3 activation, and suggest that NBs participate in the control of cell survival.
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PMID:PML induces a novel caspase-independent death process. 980 33

Arsenic is a human carcinogen. Our recent work showed that chronic (>18 wk), low-level (125-500 nM) arsenite exposure induces malignant transformation in normal rat liver cell line TRL1215. In these arsenic-transformed cells, thecellular S-adenosylmethionine pool was depleted from arsenic metabolism, resulting in global DNA hypomethylation. DNA methylation status in turn may affect the expression of a variety of genes. This study examined the aberrant gene expression associated with arsenic-induced transformation with the use of Atlas Rat cDNA Expression microarrays. Poly(A(+)) RNA was prepared from arsenic-transformed cells and passage-matched control cells, and (32)P-labeled cDNA probes were synthesized with Clontech Rat cDNA Synthesis primers and moloney murine leukemia virus reverse transcriptase. The hybrid intensity was analyzed with AtlasImage software and normalized with the sum of the four housekeeping genes. Four hybridizations from separate cell preparations were performed, and mean and SEM for the expression of each gene were calculated for statistical analysis. Among the 588 genes, approximately 80 genes ( approximately 13%) were aberrantly expressed. These included genes involved in cell-cycle regulation, signal transduction, stress response, apoptosis, cytokine production and growth-factor and hormone-receptor production and various oncogenes. These initial gene expression analyses for the first time showed potentially important aberrant gene expression patterns associated with arsenic-induced malignant transformation and set the stage for numerous further studies. Mol. Carcinog. 30:79-87, 2001. Published 2001 Wiley-Liss, Inc.
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PMID:Genetic events associated with arsenic-induced malignant transformation: applications of cDNA microarray technology. 1124 55

Arsenic is a natural substance that has been used medicinally for over 2,400 years. In the 19th century, it was the mainstay of the materia medica. A solution of potassium arsenite (Fowler's solution) was used for a variety of systemic illnesses from the 18th until the 20th century. This multipurpose solution was also primary therapy for the treatment of chronic myelogenous leukemia until replaced by radiation and cytotoxic chemotherapy. The past 100 years have seen a precipitous decline in arsenic use and, by the mid-1990s, the only recognized indication was the treatment of trypanosomiasis. Much of this decline was due to concerns about the toxicity and potential carcinogenicity of chronic arsenic administration. The rebirth of arsenic therapy occurred in the 1970s when physicians in China began using arsenic trioxide as part of a treatment for acute promyelocytic leukemia (APL). Their accumulated experience showed that a stable solution of arsenic trioxide given by intravenous infusion was remarkably safe and effective both in patients with newly diagnosed APL leukemia and in those with refractory and relapsed APL. The mechanisms of action of arsenic derivatives in this disease and other malignancies are many and include induction of apoptosis, partial cytodifferentiation, inhibition of proliferation, and inhibition of angiogenesis. Molecular studies and ongoing clinical trials suggest that, as a chemotherapeutic agent, arsenic trioxide shows great promise in the treatment of malignant disease.
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PMID:History of the development of arsenic derivatives in cancer therapy. 1133 34

Arsenic is generally recognized as a nonmutagenic carcinogen because sodium arsenite induces DNA damage only at very high concentrations. In this study we demonstrate that arsenite concentrations above 0.25 microM induce DNA strand breaks in both human leukemia cells and Chinese hamster ovary cells. Therefore, DNA damage may be involved in arsenic-induced carcinogenesis. Formamidopyrimidine-DNA glycosylase and proteinase K greatly increased DNA strand breaks in arsenite-treated cells, providing evidence that a large portion of arsenite-induced DNA strand breaks come from excision of oxidative DNA adducts and DNA-protein cross-links. Because DNA strand breaks appear only temporarily during excision repair, the level of detectable DNA strand breaks will be low at any given time point. For this reason many previous studies have only detected low levels of DNA strand breaks. We also show that catalase, and inhibitors of calcium, nitric oxide synthase, superoxide dismutase, and myeloperoxidase, could modulate arsenite-induced DNA damage. We conclude that arsenite induces DNA adducts through calcium-mediated production of peroxynitrite, hypochlorous acid, and hydroxyl radicals.
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PMID:Arsenite induces oxidative DNA adducts and DNA-protein cross-links in mammalian cells. 1146 69

Selenium, an essential trace element for humans, has been shown to have anticancer effects. Arsenic, a possibly essential ultratrace element for humans, has been used in the treatment of leukemia. Anticancer effects of selenium and arsenic have been related to their ability to induce apoptosis. Because humans are exposed to diverse trace elements simultaneously, it is important to learn their interrelationship. In this study, we demonstrate that sodium selenite (Na2SeO3) causes apoptosis at 3 microM and necrosis at high concentrations (> 3 microM) in HL-60 cells. Similarly, both sodium arsenite (NaAsO2) at 50 microM and sodium arsenate (Na2HAsO4) induce apoptosis at 500 microM and necrosis at higher concentrations (> 50 microM and > 500 microM, respectively) in HL-60 cells. Arsenite/arsenate, but not selenite, enhances AP-1 DNA-binding activity. This finding indicates different mechanisms through which apoptosis is induced by these two elements. Interestingly, we observed that HL-60 cell necrosis induced by a high concentration (> 3 microM) of selenite was essentially inhibited by arsenic (50 microM of NaAsO2 or 500 microM of Na2HAsO4), which resulted in a net effect of apoptosis. Because AP-1 DNA-binding activity was not induced in the presence of a combination of necrotic amount of selenite and apoptotic amount of arsenite/arsenate, the observed apoptosis apparently was through the mechanism used by selenite. Our results suggest, for the first time, that the toxic necrotic effect of selenite can be neutralized by arsenite/arsenate at the cellular level.
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PMID:Arsenic suppresses necrosis induced by selenite in human leukemia HL-60 cells. 1169 98

Arsenic is effective in the treatment of acute promyelocytic leukemia. Paradoxically, it is also carcinogenic. In the process of elucidating a mechanism of arsenic resistance in a leukemia cell line, NB4, we discovered that arsenic exposure causes chromosomal abnormalities, with a preponderance of end-to-end fusions. These chromosomal end fusions suggested that telomerase activity may be inhibited by arsenic. We found that arsenic inhibits transcription of the hTERT gene, which encodes the reverse transcriptase subunit of human telomerase. This effect may in part be explained by decreased c-Myc and Sp1 transcription factor activities. Decreased telomerase activity leads to chromosomal end lesions, which promote either genomic instability and carcinogenesis or cancer cell death. These phenomena may explain the seemingly paradoxical carcinogenic and antitumor effects of arsenic.
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PMID:Arsenic inhibition of telomerase transcription leads to genetic instability. 1171 46

Induction of differentiation and/or apoptosis is a new and promising approach to cancer therapy, well illustrated by the treatment of acute promyelocytic leukaemia with all-trans-retinoic acid and arsenic compounds. Treatment with all-transretinoic acid results in complete remission in 92 - 95% of patients with this disease. Using the recently advocated combination of all-transretinoic acid and chemotherapy, adverse effects such as retinoic acid syndrome have decreased, and long-term survival has improved. Chemotherapy in combination with all-trans-retinoic acid seems to be the best postremission treatment protocol, with a 5-year relapse-free survival rate of 50 - 60%. Arsenic compounds have recently proved effective in newly diagnosed and relapsed acute promyelocytic leukaemia, with complete remission rates of 80 - 90% according to most reports. As2O3, the most studied arsenic compound, can be given by intravenous infusion at a dose of 0.08 - 0.16 mg/kg daily. A course of 28 - 44 days is required to induce remission. Although the drug is safe in patients who have relapsed, severe liver damage has been observed in some newly diagnosed patients. Combined use of chemotherapy and arsenic as postremission treatment results in longer survival than arsenic alone. Although their mechanisms of action are distinct, both all-trans-retinoic acid and arsenic can modulate PML-RARalpha, an oncoprotein that has a central role in leukaemogenesis, and both can relieve ranscriptional repression by modifying chromatin structure.
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PMID:Differentiation and apoptosis induction therapy in acute promyelocytic leukaemia. 1190 60

Arsenic has been used since ancient times as a therapeutic agent. However, until recently its use in modern medicine has been restricted to the treatment of a limited number of parasitic infections. In the early 1990s, reports from China described impressive results with arsenic trioxide in patients with de novo, relapsed, and refractory acute promyelocytic leukemia (APL). Other investigators subsequently confirmed these results leading to approval of its use for relapsed or refractory APL in the United States. Investigations of this agent have demonstrated that its efficacy in APL and preclinical tumor models is dependent upon a number of mechanisms, including induction of apoptosis, effects on cellular differentiation, cell cycling, and tumor angiogenesis. Subsequent preclinical studies showed significant activity of arsenic trioxide in multiple myeloma (MM). Based on this, in a phase II trial, we have evaluated the activity of arsenic trioxide in 14 patients with relapsed MM, refractory to conventional salvage therapy. With the dose and schedule used, treatment with arsenic trioxide produced responses in three patients and prolonged stable disease in a fourth patient, with the longest response lasting 6 weeks. Although treatment was reasonably well tolerated, in these patients with extensive prior therapy, 11 developed cytopenia, five associated with infectious complications and three developed deep vein thromboses. The results of this small trial support further investigation of this novel drug for the treatment of patients with relapsed or refractory MM.
Leukemia 2002 Sep
PMID:Clinical activity of arsenic trioxide for the treatment of multiple myeloma. 1220 Jul


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