UMLS:C0699790 - FACTA Search

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Query: UMLS:C0699790 (colon cancer)
28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A non-concurrent prospective study was made on deaths from cancer and other causes occurring among 2,675 male workers at a metal refinery from 1949 to 1971. The expected number of deaths computed by applying age- and cause-specific death rates of Japanese males to these workers was compared with the observed number of deaths. Among 839 copper smelters, significantly increased mortalities were noted for lung cancer (SMR = 1,189) and colon cancer, but nor for cancer of the stomach, liver (primary) and biliary passages, pancreas and skin or for leukemia, tuberculosis, cerebrovascular diseases, heart diseases and liver cirrhosis. A dose-response relationship was demonstrated between the mortality from lung cancer and the degree of exposure. A very high excess mortality from lung cancer (SMR = 2,500) was seen among copper smelters who were considered to have been most heavily exposed to arsenic or workers who had engaged in sintering and blast furnace operations for 15 years of more before 1949. The latent period of lung cancer was 37.6 years on average, and not related to level of exposure. Twenty-six of 29 deaths from lung cancer among copper smelters occurred after they had left the refinery. Other production workers and clerical workers showed no significant excess mortality from any kind of cancer.
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PMID:A cohort study on mortality from cancer and other causes among workers at a metal refinery. 125 55

A population-based case-control study including 726 patients with colon cancer, 575 with rectum cancer, and 1400 population controls matched on age (+/- 5 yrs.) and sex was carried out to evaluate the association of ten inorganic elements, including potassium, sodium, calcium, magnesium, iron, manganese, zinc, copper, phosphorus and selenium, and other dietary factors with colorectal cancer. Single variable analysis adjusted for age and sex showed most of the ten elements, except sodium and selenium, may reduce the risk of the development of colorectal cancer. Correlation analysis indicated these eight elements correlated closely to the "vegetable factors", e.g., dietary fibre, and so on, since the major sources (about 80%) of these elements were from vegetables. Multi-variable logistic regression analysis showed nine elements (except sodium) may confound the effects of some dietary factors (such as dietary fibre and vitamin C) on the occurrence of colorectal cancer and only contribute to it. The results showed a close association between saturated fatty acid, mono-unsaturated fatty acid, dietary fibre, vitamins C and E, and colorectal cancer.
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PMID:[Relationship between colorectal cancer and ten inorganic elements]. 813 59

In the art glass industry workers run increased risks of dying from several types of cancer, cardiovascular diseases, and cerebrovascular diseases. This paper considers the diseases of glass workers in relation to exposure to particular elements, a high degree of correlation being found for some of them. Case-referent evaluations showed an association between stomach cancer and exposure to a mixture of elements, namely, arsenic, copper, nickel, and manganese, and to some extent also to lead and chromium. For colon cancer, a clearly increasing trend in risk was seen with increasing use of antimony, and to some extent also with increasing use of lead, the two elements being strongly correlated. For lung cancer no obvious correlation with any metal could be found. In addition, the risk for death from cardiovascular disease was fairly evenly distributed, although slightly more related to increasing consumption of the strongly correlated metals nickel and copper.
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PMID:Epidemiologic studies of occupational cancer as related to complex mixtures of trace elements in the art glass industry. 815 83

The bifunctional chelating agents (BFCs), 6-[p-(bromoacetamido)benzyl]-1,4,8,11-tetraazacyclotetradecane-1,4 ,8, 11-tetraacetic acid (BAT), 6-[p-(isothiocyanato)benzyl]-1,4,8, 11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid (SCN-TETA), 4-[(1,4,8,11-tetraazacyclotetradec-1-yl)methyl]benzoic acid (CPTA), and 1-[(1,4, 7,10,13-pentaazacyclopentadec-1-yl)methyl]benzoic acid (PCBA), were synthesized and conjugated to the anti-colorectal monoclonal antibody (mAB), 1A3, and antibody fragments, 1A3-F(ab')2, for radiolabeling with 64,67CU and comparison in animal models. In vivo metabolism studies were carried out in liver and kidneys in order to correlate the nature of the metabolites formed to the uptake and retention of the radiolabel in each organ. Animal biodistribution studies were performed in Golden Syrian hamsters bearing the GW39 human colon cancer tumors and in normal Sprague-Dawley rats. All conjugates showed good tumor uptake in hamsters. Biodistribution in rats showed that 64CU-BAT-2IT-1A3 had the lowest liver and kidney uptake of the intact 1A3 conjugates (p < 0.03), whereas in hamsters, there were no significant differences in liver and kidney uptake between the four intact BFC-1A3 conjugates. Tumor-bearing hamsters injected with 64CU-CPTA-1A3-F(ab')2 and 64CU-PCBA-1A3-F(ab')2 had from 3 to 7 times greater uptake in the kidneys than hamsters given 64CU-labeled BAT and SCN-TETA 1A3-F(ab')2 conjugates, while rats injected with 64Cu-CPTA-1A3-F(ab')2 and 64Cu-PCBA-1A3-F(ab')2 had nearly twice the uptake. The in vivo metabolism of the mAbs 1A3 and 1A3-F(ab')2 radiolabeled with 67Cu through the SCN-TETA, CPTA, and PCBA BFCs was investigated by excising the livers and kidneys of normal rats from 1-5 days post-injection of the radiolabeled conjugates. Liver and kidney homogenates were analyzed by size exclusion chromatography and thin layer chromatography (TLC). The size exclusion chromatography data showed that all of the 67Cu-labeled 1A3-F(ab')2 conjugates were > 85% degraded in the kidneys to small molecular weight metabolites by 1 day post-injection. In contrast, in the liver at 1 day post-injection, greater than 70% of the 67Cu-labeled 1A3 conjugates were unmetabolized. By day 5, a 35 kDa peak appeared in the liver of rats injected with the 67 Cu-labeled 1A3 conjugates, possibly due to transchelation of the 67Cu to proteins. Superoxide dismutase chromatographically elutes at the same retention time as this 67Cu-labeled metabolite. The TLC data indicate that the low molecular weight metabolite (< 5 kDa) of both 67Cu-CPTA-1A3 and 67Cu-CPTA-1A3-F(ab')2 conjugates co-chromatographed with a 67Cu-CPTA-epsilon-lysine standard. Our data suggest that chelate charge and lipophilicity play a large role in kidney retention of 64/67Cu-labeled BFC-1A3-F(ab')2 conjugates, while transchelation of the copper label appears to be the major factor for liver accumulation of 64/67Cu-labeled BFC-1A3 conjugates.
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PMID:Comparison of four bifunctional chelates for radiolabeling monoclonal antibodies with copper radioisotopes: biodistribution and metabolism. 885 65

Copper-64 (T 1/2 = 12.7 h) is an intermediate-lived positron-emitting radionuclide that is a useful radiotracer for positron emission tomography (PET) as well as a promising radiotherapy agent for the treatment for cancer. Currently, copper-64 suitable for biomedical studies is produced in the fast neutron flux trap (irradiation of zinc with fast neutrons) at the Missouri University Research Reactor. Access to the fast neutron flux trap is only possible on a weekly basis, making the availability of this tracer very limited. In order to significantly increase the availability of this intermediate-lived radiotracer, we have investigated and developed a method for the efficient production of high specific activity Cu-64 using a small biomedical cyclotron. It has been suggested that it may be possible to produce Cu-64 on a small biomedical cyclotron utilizing the 64Ni(p,n)64Cu nuclear reaction. We have irradiated both natural nickel and enriched (95% and 98%) Ni-64 plated on gold disks. Nickel has been electroplated successfully at thicknesses of approximately 20-300 mm and bombarded with proton currents of 15-45 microA. A special water-cooled target had been designed to facilitate the irradiations on a biomedical cyclotron up to 60 microA. We have shown that it is possible to separate Cu-64 from Ni-64 and other reaction byproducts rapidly and efficiently by using ion exchange chromatography. Production runs using 19-55 mg of 95% enriched Ni-64 have yielded 150-600 mCi of Cu-64 (2.3-5.0 mCi/microAh) with specific activities of 94-310 mci/microgram Cu. The cyclotron produced Cu-64 had been used to radiolabel PTSM [pyruvaldehyde bis-(N4-methylthiosemicarbazone), used to quantify myocardial, cerebral, renal, and tumor blood flow], MAb 1A3 [monoclonal antibody MAb to colon cancer], and octreotide. A recycling technique for the costly Ni-64 target material has been developed. This technique allows the nickel eluted off the column to be recovered and reused in the electroplating of new targets with an overall efficiency of greater than 90%.
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PMID:Efficient production of high specific activity 64Cu using a biomedical cyclotron. 908 Apr 73

The otherwise slow pace of contraceptive research developments has recently quickened, with new products developed, more on the way, and encouraging new data emerging about existing methods. While the 1995 UK pill scare called attention to a differential in the risk of venous thromboembolism (VTE) between pills containing levonorgestrel or norethisterone and those containing desogestrel or gestodene, there is only an extremely small level of excess mortality attributable to third-generation progestogens, less than 2 per million women per year. Tentative evidence suggests that pills with less anti-estrogenic progestogens are neutral with regard to coronary artery disease. The pill remains extremely safe for healthy young women, although additional research with larger numbers of participants is warranted. Salient research findings are that the combined oral contraceptive pill may protect against colon cancer, the pill appears to offer no protection against bone fractures, new products contain less estrogen and have a shortened pill-free interval, a WHO paper showed no significant association between cardiovascular disease and the use of oral or injectable progestogens, a UK study showed no correlation between bone density and plasma estrogen concentrations among long-term users of depot medroxyprogesterone acetate, and a WHO controlled trial found a progestogen-only method of emergency contraception to be considerably more effective in preventing expected pregnancies than the Yuzpe regimen. The T 380 copper IUD provides very high protection against intrauterine and extrauterine pregnancies for 10 years and is now available in an improved inserting mechanism, the Mirena levonorgestrel-releasing IUD system is now licensed for 5 years, and the GyneFIX IUD implant is a frameless device fixed during insertion to the fundal myometrium.
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PMID:Contraception. Slow train gathers speed. 987 50

Aberrant crypt foci (ACF) are preneoplastic lesions for colon cancer. Altered amounts of copper-zinc (CuZnSOD) and manganese (MnSOD) superoxide dismutases have been implicated in multistage carcinogesis of both rodents and humans. Dietary factors are potential modulators of both CuZnSOD and MnSOD activity. The purpose of this study was to investigate the interactive effects of dietary copper, manganese, and iron on 3,2'-dimethyl-4-aminobiphenyl (DMABP)-induced ACF and superoxide dismutase activities in weanling rats fed low or adequate copper (0.8 or 5.1 microg Cu/g diet), low or adequate manganese (0.6 or 17 microg Mn/g diet), and adequate or high iron (37 or 140 microg Fe/g diet). Twelve rats were allowed free access to each of these eight diets for 3.5 wk prior to DMABP administration and for an additional 8 wk after the first DMABP injection. Rats fed low dietary copper had 105% (P < 0.0001) higher formation of DMABP-induced ACF than those fed adequate dietary copper. Rats ingesting low rather than adequate dietary manganese had 23% higher formation of ACF, and rats ingesting high rather than adequate dietary iron had 18% higher formation of ACF. Heart total superoxide dismutase activity was significantly correlated with the number of ACF (r = -0.43, P < 0.0001) in rats administered DMABP. These results suggest that dietary alterations that affect superoxide dismutase activity may affect cancer susceptibility.
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PMID:Dietary copper, manganese and iron affect the formation of aberrant crypts in colon of rats administered 3,2'-dimethyl-4-aminobiphenyl. 1022

Previous work from our laboratory indicated that the bile salt sodium deoxycholate (NaDOC) induced apoptosis in cultured cells and in normal goblet cells of the colonic mucosa. We also reported that the normal-appearing flat mucosa of patients with colon cancer exhibited apoptosis resistance. Using immunofluorescence in conjunction with confocal microscopy, we now report that high physiological concentrations (0.5 mM) of NaDOC result in the formation of nitrotyrosine residues, a footprint for the formation of reactive nitrogen species, including peroxynitrite, in plasma membrane-associated proteins of HT-29 cells. Because peroxynitrite is formed from the reaction between nitric oxide and superoxide anion, we specifically looked at the role of nitric oxide and superoxide anion in NaDOC-induced apoptosis. Pretreatment of cells with the inhibitor/antioxidants, N-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase, copper (II) 3,5-diisopropyl salicylate hydrate, a superoxide dismutase mimetic compound, and Trolox, a water-soluble analog of alpha-tocopherol, alone or in combination, sensitized cells to apoptosis induced by 0.5 mM NaDOC. These results suggest that nitric oxide may be part of a signaling pathway that is responsible for apoptosis resistance. The results also indicate that nitric oxide does not appear to protect cells against NaDOC-induced apoptosis by scavenging superoxide anion.
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PMID:Role of nitric oxide and peroxynitrite in bile salt-induced apoptosis: relevance to colon carcinogenesis. 1069 73

Low dietary copper has been shown to decrease the expression of various protein kinase C (PKC) isozymes and increase the risk of colon cancer development in experimental animals. The purpose of this study was to investigate the relationship between dietary copper and carcinogen administration on PKC isozyme accumulation and aberrant crypt foci (ACF) formation in rats fed 0.9 and 7.7 microg Cu/g diet. After 24 and 31 d on the diets, the rats were injected with either dimethylhydrazine (DMH) (25 mg/kg i.p.) or saline and killed at two time points (2 wk and 8 wk after DMH). Rats fed low dietary copper had significantly lower (p<0.0001) hematocrits, hemoglobin, ceruloplasmin activity and plasma and liver copper concentrations than rats fed adequate dietary copper. Ingestion of low dietary copper significantly (p<0.005) increased the formation of DMH-induced ACF (116.8 vs 59.6). Low dietary copper significantly (p<0.05) decreased the concentration of PKC alpha, delta, and zeta in the colon at 2 wk but not at 8 wk. Thus, changes in PKC isoform protein concentration may be related to increased susceptibility of copper-deficient animals to colon cancer.
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PMID:Dietary copper and dimethylhydrazine affect protein kinase C isozyme protein and mRNA expression and the formation of aberrant crypts in colon of rats. 1167 41

Lysyl oxidase (LOX), a copper-dependent amine oxidase, has been implicated in tumor suppression and cell growth regulation. The chromosomal locus of LOX, 5q23, is affected by loss of heterozygosity (LOH) in colon cancer, suggesting that the LOX gene could be affected by LOH and consequently, loss or reduction of LOX function contribute to the tumorigenic process. Identification of microsatellite markers within the LOX locus has allowed us to map the LOX gene within the 5q23.1 region. Analysis of this locus and flanking loci in matched tumor and blood DNA samples from a panel of colorectal cancer patients, demonstrated that 38% (16/42) of informative samples were affected by LOH or allelic imbalance. Furthermore, 75% (6/8) of these tumor samples were shown to have significantly reduced LOX mRNA levels. Similar reduction in LOX levels were detected in a panel of matched normal colon and colon tumor samples. Tumor samples demonstrating LOH by RFLP, were subject to mutational analysis, including RT-PCR, exonic deletion detection by PCR, cDNA and genomic DNA sequencing, and were found to have a spectrum of alterations and mutations affecting the LOX gene. These results confirm that loss or reduction of LOX function during tumor development is a direct consequence of somatic mutations and is associated with colon tumor pathogenesis.
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PMID:Somatic mutations of the lysyl oxidase gene on chromosome 5q23.1 in colorectal tumors. 1180 90

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