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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Parental occupational exposures might affect childhood cancer in the offspring through genetic changes in the ovum or sperm or through transplacental carcinogenesis. The 24 published epidemiologic studies of this association have all used case-control designs, with controls generally selected from birth certificates or from general population sampling. Occupational exposures were inferred from job titles on birth certificates or through interviews. A large number of occupation-cancer associations have been reported, many of which were not addressed or not confirmed in other studies. Several associations have been found with consistency: paternal exposures in hydrocarbon-associated occupations, the petroleum and chemical industries, and especially paint exposures have been associated with brain cancer; paint exposures have also been linked to leukemias. Maternal exposures have received much less attention, but studies have yielded strongly suggestive results linking a variety of occupational exposures to leukemia and brain cancer. The primary limitations in this literature are the inaccuracy inherent in assigning exposure based on job title alone and imprecision due to limited study size. Although no etiologic associations have been firmly established by these studies, the public health concerns and suggestive data warrant continued research.
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PMID:Parental occupation and childhood cancer: review of epidemiologic studies. 227 30

Over the past two decades, marked shifts have occurred in cancer mortality in the United States, the United Kingdom, and the Federal Republic of Germany. Stomach cancer mortality has declined sharply, while brain cancer and multiple myeloma increased nearly twofold for persons ages 75 to 84. Total cancer incidence in the United States, excluding lung cancer, has risen 27% since 1950, adjusted to the aging of the population. The origins of these trends are not known. The diet in the developed countries includes a number of naturally occurring, powerful anticarcinogens and carcinogens. To evaluate the role of these substances in the prevention and causation of human cancer, this paper reviews existing toxicologic and epidemiologic data. These data indicate that naturally occurring substances in food influence cancer initiation, promotion, progression, and demotion by a number of mechanisms, including (1) covalent binding to DNA of naturally occurring anticarcinogenic compounds to block the initiation of carcinogenesis; (2) induction of biotransforming enzymes such as cytochrome P450 and mixed-function oxidase (MFO) which can reduce carcinogenicity; (3) inhibition of tumor promotion by compounds such as retinol, tocopherol, and organosulfates found in garlic, onions, fruits, and vegetables; and (4) physical alteration of carcinogens by food constituents or by food preparation and handling so as to alter carcinogenicity. Systems have been proposed for estimating the relative ranking for humans of individually tested, experimental carcinogens, including some constituents of food. While qualitatively useful, such systems as the HERP Index do not take into account important interactions among naturally occurring and synthetic constituents in foods, nor do they permit examination of the possible role of evolved resistance. Common mixtures in food must be tested for carcinogenicity in human tissue cultures and in long-term rodent bioassays. Such studies need to examine whether the action of synthetic organic carcinogens may be inhibited by potent naturally occurring anticarcinogens.
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PMID:Natural anticarcinogens, carcinogens, and changing patterns in cancer: some speculation. 268 27

Many investigations suggested relations between fat soluble vitamin levels in blood and incidence of cancer. These studies are concerning both therapeutical efficiency of vitamins intake, seric levels and cancer risk, and the supposed correlation between blood fat soluble vitamin levels and the cancer localization. The purpose of the present study was to investigate whether the alterations of fat soluble vitamin levels (A-vitamin, beta-carotene and alpha-tocopherol) were correlated not only to carcinogenic processes but also to the localizations of their developments. In a former article, we have found that an abnormal ketone derivative of D3 vitamin (1-keto-24-methyl-25-hydroxycholecalciferol) or carcinomedin was present in the serum of all cancer patients and absent in that of healthy control subjects. Serum levels of the four above substances were determined in 1068 subjects suffering from differently localized cancers and in 880 healthy subjects. A statistical multidimensional analysis of data led a separate five groups of cancer types (p less than 0.001). Within each group alterations of vitamin spectra, compared to controls, were identical; between groups they were significantly different. These groups were: anal and intestinal cancer; pancreatic, hepatic, oesophageal and gastric cancer; laryngeal and lung cancer; uro-genital and breast cancer; brain cancer. All these groups are statistically different from the reference one (p less than 0.001). This grouping roughly corresponds to the embryologic origin of affected organs. This suggests that carcinogenesis may alter fat soluble vitamin metabolism, specifically in various forms of cancer, or these alterations of vitamin metabolism are in some way involved in the carcinogenic process.
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PMID:Fat soluble vitamins and cancer localization associated to an abnormal ketone derivative of D3 vitamin: carcinomedin. 344 Jul 11

The questions of whether and how N-nitroso compounds (NOC) may be inducing cancer in humans are discussed. The principal subjects covered include nitrite-derived alkylating agents that are not NOC, reasons for the wide tissue specificity of carcinogenesis by NOC, the acute toxicity of nitrosamines in humans, mechanisms of in vivo formation of NOC by chemical and bacterial nitrosation in the stomach and via nitric oxide (NO) formation during inflammation, studies on nitrite esters, use of the nitrosoproline test to follow human gastric nitrosation, correlations of nitrate in food and water with in vivo nitrosation and the inhibition of gastric nitrosation by vitamin C and polyphenols. Evidence that specific cancers are caused by NOC is reviewed for cancer of the stomach, esophagus, nasopharynx, urinary bladder in bilharzia and colon. I review the occurrence of nitrosamines in tobacco products, nitrite-cured meat (which might be linked with childhood leukemia and brain cancer) and other foods, and in drugs and industrial situations. Finally, I discuss clues from mutations in ras and p53 genes in human tumors about whether NOC are etiologic agents and draw some general conclusions.
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PMID:Role of N-nitroso compounds (NOC) and N-nitrosation in etiology of gastric, esophageal, nasopharyngeal and bladder cancer and contribution to cancer of known exposures to NOC. 760 May 41

Aging-related carcinogenesis has been attributed to inherent genetic instability, which manifests in a multistep fashion by activation of oncogenes and inactivation of tumor suppressor genes. Malignant brain tumor cells display multiple-characteristic acquired genetic abnormalities in oncogenes and tumor suppressor genes. Age-specific malignant brain tumor mortality rates in the United States from 1962 to 1988 were interpreted by longitudinal Gompertzian analysis. Utilizing a thermodynamic perspective of the Strehler-Mildvan modification of the Gompertz relationship between mortality and aging, a measure of the rate of increase in informational entropy for those genetic factors involved in the carcinogenesis of malignant brain tumor was determined. Aging-related carcinogenesis can be viewed as a natural consequence of increasing informational entropy of the genome.
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PMID:Carcinogenesis, genetic instability and genomic entropy: insight derived from malignant brain tumor age specific mortality rate dynamics. 799 60

The expression of Bfl-1 gene, a novel Bcl-2 related gene, was determined by Northern blot analysis using a radiolabeled cDNA specific for Bfl-1 gene in 82 surgically resected tissue specimens of 28 gastric cancers, 15 colon cancers, nine breast cancers, eight bone and soft tissue sarcomas, five ovarian cancers, nine colon adenomas and eight gastric adenomas. A high rate of expression was observed in gastric and colon cancer, at 86 and 93%, respectively. In breast cancer, bone and soft tissue sarcoma and ovarian cancer, the expression rate was 33, 25 and 40%, respectively. In stomach cancer, the expression rate of Bfl-1 gene in metastatic lymph nodes was 82%, which was higher than 50% of the primary sites (p < 0.02). The intensity of RNA bands of the gastric cancer specimens was compared according to the stage, demonstrating that there was no difference in the expression levels of Bfl-1 gene between the stages in both primary sites and metastatic lymph nodes. Bfl-1 gene was expressed in three (33%) out of nine adenomas of the colon, while it was not detected in all eight gastric adenomas, We also examined the RNA expression of Bfl-1 gene in 22 human cancer cell lines consisting of five stomach cancer, four squamous cell carcinoma, three lung cancer, three cervical cancer, two colon cancer, two brain cancer, two leukemia and one osteosarcoma cell lines. Bfl-1 gene band was detected in one (5%) cervical cancer cell line, SiHa. The results of cancer tissue specimens indicate that Bfl-1 gene may play an important role in carcinogenesis of human cancers and may be involved in a relatively early phase of the adenoma-carcinoma sequence in colon cancer development. However, the mechanism responsible for the very low rate of expression in established cell lines is not clearly understood and further investigation is necessary to clarify the mechanism involved.
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PMID:Expression of a novel Bcl-2 related gene, Bfl-1, in various human cancers and cancer cell lines. 949 79

We update our 1997 publication by reviewing 29 new reports of tests of magnetic fields (MFs) in six different in vivo animal models of carcinogenesis: 2-year, lifetime, or multigeneration exposure studies in rats or mice; and promotion/progression models (rat mammary carcinoma, rat liver focus, mouse skin, several models of human leukemia/lymphoma in rats and mice, and brain cancer in rats). Individual experiments are evaluated using a set of data quality criteria, and summary judgments are made across multiple experiments by applying a criterion of rough reproducibility. The potential for carcinogenicity of MFs is discussed in light of the significant body of carcinogenesis data from animal bioassays that now exists. Excluding abstracts, approximately 80% of the 41 completed studies identified in this and our previous review roughly satisfy data quality criteria. Among these studies, the criterion for independent reproducibility is not satisfied for any positive results but is satisfied for negative results in chronic bioassays in rats and mice and for negative results in both promotion and co-promotion assays using the SENCAR mouse skin model. Results of independent replication studies using the rat mammary carcinoma model were conflicting. We conclude that long-term exposure to continuous 50- or 60-Hz MFs in the range of 0.002-5 mT is unlikely to result in carcinogenesis in rats or mice. Though results of most promotion/progression assays are negative, a weak promoting effect of MFs under certain exposure conditions cannot be ruled out based on available data.
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PMID:Assessing the potential carcinogenic activity of magnetic fields using animal models. 1069 25

Electric and magnetic fields (EMF) are associated with the production, transmission, and use of electricity; thus, the potential for human exposure is high. These electric and magnetic fields are predominantly of low frequency (60 Hz in the United States and 50 Hz in Europe) and generally of low intensity. Epidemiology studies have suggested a potential for increased breast cancer, brain cancer, and leukemia rates with increasing magnetic field exposure. Therefore, given the widespread exposure to low-intensity, 60-Hz magnetic fields in industrialized societies, standard toxicology studies and long-term carcinogenesis studies were conducted using traditional rodent models. Male and female F344/N rats and B6C3F1mice were exposed to 60-Hz magnetic fields by whole-body exposure for 2 years. 2-YEAR STUDY IN RATS: Groups of 100 male and 100 female rats were exposed to 60-Hz magnetic fields at intensities of 0.02, 2, or 10 G for 18.5 hours per day, 7 days per week, for 106 weeks. Groups of 100 male and 100 female control rats were housed in the same exposure chambers without applied magnetic fields. Additional groups of 100 male and 100 female rats were intermittently exposed (1 hour on and 1 hour off) to a 10 G 60-Hz field 18.5 hours per day, 7 days per week, for 106 weeks. The highest field intensity (10 G) is approximately 5,000-fold greater than what was considered high intensity for homes in epidemiology studies in humans. Survival and Body Weights: Survival and mean body weights of exposed groups of male and female rats was similar to those of the control groups. Pathology Findings: The incidences of thyroid gland C-cell adenoma and carcinoma in 0.02 G male rats, adenoma in 2 G males, and adenoma or carcinoma (combined) in 0.02 and 2 G males were significantly greater than in the control group. The incidence of mononuclear cell leukemia in males in the 10 G intermittent group was significantly less than in the control group. 2-YEAR STUDY IN MICE: Groups of 100 male and 100 female mice were exposed to 60-Hz magnetic fields at intensities of 0.02, 2, or 10 G for 18.5 hours per day, 7 days per week, for 106 weeks. Groups of 100 male and 100 female control mice were housed in the same exposure chambers without applied magnetic fields. Additional groups of 100 male and 100 female mice were intermittently exposed (1 hour on and 1 hour off) to a 10 G 60-Hz field 18.5 hours per day, 7 days per week, for 106 weeks. Survival and Body Weights: Survival of male mice exposed to 10 G was significantly less than that of control mice after 2 years; survival of all other exposed groups of mice was similar to that of control mice. Mean body weights of exposed groups of male and female mice were similar to those of the control groups throughout the study. Pathology Findings: The incidences of alveolar/bronchiolar adenoma were significantly decreased in 0.02 and 2 G male mice and 2 G female mice relative to the control groups; the incidences of alveolar/bronchiolar adenoma or carcinoma (combined) were significantly less in males and females exposed to 2 G than in the control groups. In female mice, the incidence of malignant lymphoma in the 10 G intermittent group was significantly less than in the controls. CONCLUSIONS: Under the conditions of these 2-year whole-body exposure studies, there was equivocal evidence of carcinogenic activity of 60-Hz magnetic fields in male F344/N rats based on increased incidences of thyroid gland C-cell neoplasms in the 0.02 and 2G groups. There was no evidence of carcinogenic activity in female F344/N rats or male or female B6C3F1 mice exposed to 0.02, 2, or 10 G, or 10 G intermittent 60-Hz magnetic fields. In exposed rats and mice there were no increased incidences of neoplasms at sites for which epidemiology studies have suggested an association with magnetic fields (brain, mammary gland, leukemia).
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PMID:NTP Toxicology and Carcinogenesis Studies of 60-HZ Magnetic Fields IN F344/N Rats and B6C3F1 Mice (Whole-body Exposure Studies). 1256 43

Epigallocatechin-3-gallate (EGCG), the major green tea polyphenol, can reach the brain following oral intake and could thus act as an anti-tumoral agent targeting several key steps of brain cancer cells invasive activity. Because integrin-mediated extracellular matrix recognition is crucial during the cell adhesion processes involved in carcinogenesis, we have investigated the effects of EGCG on different cellular integrins of the pediatric brain tumor-derived medulloblastoma cell line DAOY. Using flow cytometry, we report the levels of expression of several cell surface integrins in DAOY. These include high expression of alpha2, alpha3, and beta1 integrins, as well as alphav and beta3 integrins. Moreover, we provide evidence that EGCG can antagonize DAOY cell migration specifically on collagen by increasing cell adhesive ability through specific gene and protein upregulation of the beta1 integrin subunit. Our results suggest that this naturally occurring green tea polyphenol may thus be used as a nutraceutical therapeutic agent in targeting the invasive character of medulloblastomas.
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PMID:Medulloblastoma cell invasion is inhibited by green tea (-)epigallocatechin-3-gallate. 1458 30

Identifying gene-specific alterations in cancer genomes has revealed molecules that are causal effectors of carcinogenesis and specific targets for cancer molecular diagnosis and molecular-based cancer therapies. Whole-genome analyses of many cancer genomes at the resolution of single genes is thus a desirable yet incompletely realized goal that could expedite progress in cancer diagnosis and treatment. Although methods for routine whole-genome sequencing or high-resolution epigenetic measurements are currently under development, high-resolution measurements of gene copy number, or 'gene dosage', are now underway in several laboratories. Digital karyotyping, array comparative genomic hybridization, and single nucleotide polymorphism arrays are techniques that have the potential to detect gene amplification, homozygous deletion and loss of heterozygosity at or below the average length of single genes. Recently, digital karyotyping of a small number (<20) of colon and brain cancer genomes has revealed tumor cases with significant genetic dosage alterations affecting few and, in some cases, only one complete gene. These experiments suggest that gene-specific gene dosage alterations may be sufficiently frequent to enable the identification of promising tumor gene candidates in small-scale experiments. The purpose of this review is to describe our understanding of cancer as a genetic disease, review the basic principles, methodologies and interpretational issues of traditional and high-resolution whole-genome screens, and describe the potential of our first detailed look at whole cancer genomes for progress in the understanding and treatment of cancer.
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PMID:Digital karyotyping technology: exploring the cancer genome. 1625 33


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