Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A case-control study was conducted 1) to determine whether maternal prenatal drug consumption increases the risk of neuroblastoma in the child and, if so, 2) to see if the size of the risk depends on whether the case is inherited or sporadic. Mothers of children with newly diagnosed neuroblastoma (n = 101) were compared with mothers of children newly diagnosed with other forms of childhood cancer (n = 690). Cases and controls were selected from the population of childhood cancer patients at St. Jude Children's Research Hospital, Memphis, Tennessee, between 1979 and 1986. The patients' mothers were interviewed to ascertain their prenatal medication, alcohol, and tobacco consumption patterns. Unconditional logistic regression models were used to adjust for maternal age at birth, patient age at diagnosis, race, social class, exposure to x-ray, miscarriage, and other confounding variables. Adjusted odds ratios were estimated for the total sample and for subgroups that had a higher probability of containing inherited cases. Drugs associated with neuroblastoma case status include diuretics for hypertension (odds ratio (OR) = 4.1, 95 percent confidence interval (CI) 1.0-16.9), tranquilizers (OR = 2.1, 95 percent CI 1.1-4.3), nonprescription pain relievers (OR = 1.9, 95 percent CI 1.1-3.1), and cigarettes (OR = 1.9, 95 percent CI 1.1-3.2). The odds ratios for maternal prenatal drug consumption for the group with inherited cases and the total sample were approximately the same. This equality is inconsistent with predictors based on Knudson's two-stage model of carcinogenesis.
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PMID:Influence of the mother's prenatal drug consumption on risk of neuroblastoma in the child. 151 82

The chance that alternatives will completely replace animals for toxicology research in the foreseeable future is nil. Continual refinement of animal toxicity and carcinogenesis studies, however, can be an effective means of reducing the numbers of animals used and conserving time and resources without compromising scientific quality. We must continue to strive to find species and strains that can metabolize chemicals similar to humans, are small enough to be housed in large numbers, and have low prevalence of spontaneous lesions with sufficient life span to express the toxic and carcinogenic potential of chemicals. Adequate care of animals with control of variables such as light, temperature, diet, bedding, diseases, and genetic characters of laboratory animals will decrease the variability. Humane considerations and euthanasia of animals with large masses and other conditions interfering with eating and drinking, major injuries and ulcers related to husbandry and treatment, and diseases indicating pain and suffering will help not only to alleviate further pain and distress but also to facilitate collection of tissues without secondary complications for detection of chemical treatment-related lesions. Limiting the duration of studies to decrease the variability due to age-associated changes will also refine long-term studies. Other considerations for refinement of carcinogenesis studies include selection of the most sensitive sex of one or more species for evaluation of selected chemicals in a class where toxic and carcinogenic potential of other representative chemicals are known. Genetically engineered animal models with known oncogenes may reduce the duration and increase the sensitivity of carcinogenesis studies with a reduction in the use of animals.
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PMID:Refinement of long-term toxicity and carcinogenesis studies. 185 28

The current therapeutic approach to peptic ulcer disease includes agents that reduce gastric acidity and hence peptic activity, inactivate or adsorb pepsin, create a physical barrier against the effects of acid and pepsin, or enhance mucosal defence. Profound gastric acid reduction may predispose to infection, and it has been suggested that carcinogenesis is possible, although a cause-effect relationship has never been established. The side-effects of therapy are well-described, and may limit the therapeutic approach. Healing rates correlate closely with acid suppression in duodenal ulcer, but not entirely in gastric ulcer. Maintenance therapy lowers the relapse rate, but does not alter the ulcer diathesis. The optimal strategy for long-term management remains unclear, but in the future one should consider outcome measures which include a decrease in pain, improvement in the quality of life, reduction work loss, and a reduction of complications, in addition to ulcer healing. The ideal therapy should be efficacious, safe, and convenient--with no side-effects--and cost-effective. New agents should suppress acid and peptic activity, while enhancing the gastric mucosal defence mechanisms (such as mucosal blood flow, mucus, and bicarbonate secretion) and stimulating gastric cellular regeneration and restitution.
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PMID:The limitations of current therapy in peptic ulcer disease. 330 47

These experiments were designed to define the conditions necessary for the modification of radiation-induced transformation in C3H/10T1/2 cells by TPA and protease inhibitors. The results show that: (i) the lowest effective dose of various protease inhibitors to suppress transformation in vitro varies over several orders of magnitude; on a molar basis, the inhibitors of chymotrypsin appear to be the most effective protease inhibitors at suppression of radiation-induced transformation in vitro, (ii) the protease inhibitors antipain and the Bowman-Birk (soybean) protease inhibitor have no effect on radiation transformation when present only during irradiation, (iii) the protease inhibitor antipain can suppress radiation transformation in vitro when applied to proliferating "initiated' cells as late as 10 days and 13 cell divisions post-irradiation, and (iv) TPA treatment following a 10-day protease inhibitor (anti-pain) exposure of X-irradiated "initiated' cells does not lead to promotion in vitro. These results suggest that protease inhibitor treatment of the initiated cells has irreversibly reverted cells to their original or "uninitiated' condition which existed before irradiation.
Carcinogenesis 1985 Oct
PMID:The conditions for the modification of radiation transformation in vitro by a tumor promoter and protease inhibitors. 404 73

This review article touches on various categories of research that have been expanded or made possible predominantly by funding through the National Cancer Program of the National Cancer Institute and the American Cancer Society. Under diagnosis, categories mentioned are biological markers, chromosome banding techniques, fluorescent-activated cell sorter identification of cell surface antigens, ultrastructural studies with electron microscopy, histochemical, radiologic, ultrasonographic, thermographic, angiographic techniques, nuclear magnetic resonance imaging, radioactively labeled compounds that attach to specific tumor cell surface receptors, and other agents that are preferentially taken up by tumor tissues. Predictive tests include human tumor stem cell assays, sister chromatid exchange assay, and hormone receptor assays. The techniques listed under therapy include hyperthermia, immunotherapy, chemotherapy, radiosensitizing compounds, and the supportive measures of hyperalimentation and other nutritional manipulations, psychological reinforcement, rehabilitative efforts, bone marrow transplants, blood component therapy, protective "germ-free" environments, and pain control. Drug delivery systems, animal and cell culture models, and prevention of carcinogenesis are also mentioned.
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PMID:Cancer 1980: achievements, challenges, and prospects. 617 12

An increasing amount of clinical data indicates that low-dose methotrexate therapy for rheumatoid arthritis is both effective and free of serious side effects. Since 1967 we treated 78 patients with definite or classic rheumatoid arthritis who showed inadequate response to conventional therapy. Up to 15 mg of methotrexate was given weekly by the intramuscular route. Morning stiffness, severity of pain at rest and with activity, extent of active synovitis, functional capacity, change in steroid dosage, complete blood count, erythrocyte sedimentation rate, and gamma glutamyl transpeptidase were monitored. Overall assessment indicated that 45 of the 78 (58 percent) patients showed marked improvement or complete remission, usually within four weeks. When maximum improvement was obtained, most patients were switched to oral therapy with a variable degree of success, and dosage was decreased as tolerated. No serious toxicity was noted. In 34 patients a total of 67 liver biopsy specimens were obtained, some after as long as 15 years of therapy. Minor changes observed are the same as in patients with rheumatoid arthritis not treated with methotrexate. Because the risks did not appear justified, routine annual biopsies were discontinued. In contrast to other cytotoxic drugs, no carcinogenesis has been demonstrated with methotrexate. It appears that methotrexate is approximately as effective as intramuscular gold and D-penicillamine but that it has a quicker onset of response and less serious toxicity.
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PMID:Methotrexate therapy in rheumatoid arthritis: 15 years experience. 666 Feb 41

The introduction of the oral steroid pill and the intrauterine device represents an improved, effective and acceptable means of regulating fertility, but this has been tempered by concern over their safety. Although the Pill frequently is associated with minor side effects, serious complications are rare. The issues of greatest concern are the relationship to carcinogenesis, for which there is no evidence of greater risk in general, and that to the circulatory system diseases, with evidence to indicate an increased risk, albeit relatively small, but more particularly in older women who smoke. The device, although frequently not tolerated because of pain and bleeding, very rarely carries the risk of serious consequences, and its relationship to infection, both in early pregnancy and in the oviduct, is yet to be resolved. The benefits derived from these methods should not go unnoticed, through providing the woman with a freedom from fear of pregnancy previously not possible.
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PMID:Safety of modern contraceptive technology. Current status. 698 81

Forty-one patients who underwent one technic of fiber implantation for pattern baldness were studied. Complications were frequent and included rejection of fibers, infection, facial swelling, pain, pruritus, and scarring. In addition, patients incurred risks of carcinogenesis from deeply embedded bits of fiber and also loss of their own natural hair. Fiber implantation is an unsuccessful method of hair restoration, and its use has been discouraged by state and federal agencies.
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PMID:Fiber implantation for pattern baldness. Review of complications in forty-one patients. 701 3

Research on contraceptive implants began when it was learned that steroids could be released from Silastic rubber capsules. The six-capsule Silastic drug delivery system, which would eventually be called Norplant, was by 1974 perfected and prepared for clinical trials. By 1978, data had accumulated to indicate a failure rate for Norplant after two years of only 0.6%, so Leiras Pharmaceuticals of Turku, Finland, was licensed in 1983 to manufacture Norplant, and Finland became the first country to give regulatory approval for distribution of the new contraceptive. The World Health Organization, after a 1984 evaluation, concluded that the Norplant system is an effective, reversible, long-term method of fertility regulation which is particularly appropriate for women in need of long-term contraceptive protection. Wyeth-Ayerst Laboratories began to distribute the device in the US after it met US Food and Drug Administration approval. 24 countries have now approved Norplant for distribution and use among women. This paper describes the Norplant contraceptive system, its mechanism of action, insertion and removal, effectiveness, contraindications, and adverse effects with regard to menstrual problems, medical problems, infection or pain, drug interactions, ectopic pregnancy, foreign body carcinogenesis, and other adverse reactions. It also notes use benefits in terms of contraceptive action, convenience, the reduction of adverse reactions for former oral contraception users, and the prevention of anemia, and lists categories of potential acceptors and women who may not wish to use Norplant.
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PMID:Implantable contraception. 770 29

Capsaicin (8-methyl-N-vanillyl-6-nonenamide) is a primary pungent and irritating principle present in chilies and red peppers which are widely used as spices. Because of its selective effects on the functions of a defined subpopulation of sensory neurons, capsaicin is currently used as a versatile tool for the study of pain mechanisms and also for pharmacotherapy to treat several pain disorders. Considering the frequent consumption of capsaicin as a food additive and its current medicinal use, correct assessment of hazardous effects of this compound is important. Mutagenic and carcinogenic activities of capsaicin and chili extracts have been studied, but results are conflicting. Mammalian metabolism of capsaicin has been also reported. Capsaicin appears to interact with xenobiotic metabolizing enzymes, particularly microsomal cytochrome P450-dependent monooxygenases which are involved in activation as well as detoxification of various chemical carcinogens and mutagens. Recent studies have shown that hepatic cytochrome P450 2E1 catalyzes the conversion of capsaicin to reactive species such as the phenoxy radical intermediate capable of covalently binding to the active site of the enzyme as well as tissue macromolecules. While covalent modification of protein and nucleic acids leads to toxicity including necrosis, mutagenesis, and carcinogenesis, suicidal inhibition of microsomal cytochrome P450 may prohibit further activation of capsaicin and also of other toxic xenobiotics. Results from recent studies indicate that capsaicin possesses the chemoprotective activity against some chemical carcinogens and mutagens.
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PMID:Capsaicin, a double-edged sword: toxicity, metabolism, and chemopreventive potential. 774 93


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