Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006826 (cancer)
 1,092,456 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recognition thresholds for the four basic tastes (salt, sour, sweet and bitter) were tested by the forced-choice technique in 27 patients with small-cell lung cancer, and 22 weight-matched control patients with non-malignant diseases. No significant differences in threshold concentrations could be demonstrated. When patients who were losing weight were compared with weight-stable patients, significantly lower taste thresholds for bitter substances were found in weight losing groups in both cancer and control patients. Small-cell lung cancer patients who responded to therapy had obtained an increased threshold for bitter taste at the time of reevaluation than at the time of diagnosis, an effect that may be explained by the chemotherapeutic regimen. The results suggest that in patients with small-cell lung cancer it is not the cancer disease per se but the weight loss that often accompanies it that causes an increased taste sensitivity for bitter substances.
J Cancer Res Clin Oncol 1991
PMID:Taste thresholds in patients with small-cell lung cancer. 184 1

Terpentecin and clerocidin, microbial terpenoides, have been known to be potent antitumor antibiotics. However, the critical biochemical target of these terpenoides has not been identified. Our present studies, using purified mammalian topoisomerase II, have shown that terpentecin and clerocidin induce topoisomerase II-mediated DNA cleavage in vitro with comparable potency to that of demethylepipodophyllotoxin ethylidene-beta-D-glucoside. These terpenoides produced a similar DNA cleavage pattern which is distinctly different from those generated in the presence of the known topoisomerase poisons, demethylepipodophyllotoxin ethylidene-beta-D-glucoside and 4'-(9-acridinylamino)methanesulfon-m-anisidide. Brief heating at 65 degrees C, which abolishes completely the cleavable complex with demethylepipodophyllotoxin ethylidene-beta-D-glucoside, of the reaction mixture containing these terpenoides resulted in slight reduction in DNA cleavage. Thus, differently from other topoisomerase II-active antitumor agents, terpentecin and clerocidin induce formation of a cleavable complex which is stable for heat or salt treatments. The lack of significant DNA binding or intercalation activity of terpentecin and clerocidin suggests that topoisomerase II is a cellular target for these drugs.
Cancer Res 1991 Jun 01
PMID:Induction of a heat-stable topoisomerase II-DNA cleavable complex by nonintercalative terpenoides, terpentecin and clerocidin. 185 67

A new tetrazolium analog of 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) was evaluated as a substitute for MTT in the microculture screening assay for in vitro cell growth. This new tetrazolium compound, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2- (4-sulfophenyl)-2H-tetrazolium, inner salt (MTS), in the presence of phenazine methosulfate (PMS), gave a water-soluble formazan product that had an absorbance maximum at 490-500 nm in phosphate-buffered saline. The amount of colored product formed was proportional to the number of cells and the time of incubation of the cells with MTS/PMS. MTS/PMS was reactive in all the cell lines tested which included mouse leukemia L1210 cells, mouse Ehrlich tumor cells, mouse 3T3 fibroblasts, and human colon tumor cells (HT-29). HT-29 and 3T3 fibroblasts reduced MTS/PMS more efficiently than they reduced MTT. Comparable to the amount of product formed from MTT, MTS/PMS gave excellent product formation. The IC50 value for pyrazoloimidazole obtained using MTS/PMS was 200 microM; for 5-fluoro-2'-deoxyuridine, the IC50 value was 0.9 nM. These values compared very favorably with the IC50 values obtained by direct cell counts. Further, the same IC50 values were obtained when the absorbances of the formazan product in the 96-well plates were determined after different times of incubation.
Cancer Commun 1991 Jul
PMID:Use of an aqueous soluble tetrazolium/formazan assay for cell growth assays in culture. 186 54

A relationship between salt intake and the occurrence of stomach cancer has been suggested by both epidemiologic and experimental data. To test this hypothesis, urinary excretion of salt in 24 hours and dietary intake of salt were measured in four male populations with different levels of stomach cancer mortality. Age-adjusted mortality rate of stomach cancer showed a high correlation (r2 = 0.995) with the average amount of salt excretion in 24-hour urine. This strong correlation, however, was not shown (r2 = 0.265) with dietary salt intake calculated from the standard food-composition table. The results confirmed the important role of salt in the development of stomach cancer in Japan, and raised the problem of evaluating the level of salt intake by using the uniform composition table.
Cancer Causes Control 1991 May
PMID:Urinary salt excretion and stomach cancer mortality among four Japanese populations. 187 46

A hospital-based, multicenter, case-control study has been performed in Poland covering 741 incident stomach-cancer cases (520 males and 221 females) and the same number of controls. All stomach-cancer diagnoses were evaluated for histologic type according to the Lauren criteria. Fifty-one percent were of the intestinal type, 35 percent of the diffuse type, and 8.5 percent of the mixed type. The frequency of consumption of individual food items and several food groups was analyzed and the association of various foods with stomach cancer risk was evaluated after controlling for sex, age, occupation, education, and residency. Increased consumption of sausages was related significantly to gastric cancer risk, whereas increased consumption of cheese products, nonwhite bread, vegetables, and fruit was associated with decreased risk. A particularly strong decrease in risk was associated with consumption of radishes and onions. When consumption of fruits and vegetables, sausages, nonwhite bread, and cheese were introduced simultaneously in a multivariate model, independent effects were found only for fruit and vegetables, sausages, and nonwhite bread. The use of table salt, the frequency of eating hot meals, and an irregular eating pattern were also associated with increased risk, while additional consumption of fruit between meals showed reduced risk. If a reduction in vegetable and fruit consumption took place after marriage, an increased risk for stomach cancer was found, whereas augmented consumption of these food items after marriage decreased the risk. Separate risk models were calculated for stomach cancer of the intestinal and diffuse types, but both histologic varieties showed the same pattern of associations with dietary risk factors.
Cancer Causes Control 1991 Jul
PMID:Dietary risk factors in intestinal and diffuse types of stomach cancer: a multicenter case-control study in Poland. 187 52

The structures of the mirror image (+)- and (-)-trans-anti-adducts of 7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene to guanine N2 have been of great interest because the high biological activity of 7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene in mammalian mutagenesis and tumorigenesis has been attributed to the predominant (+)-trans-anti-adduct. We have carried out new potential energy minimization studies, involving wide-scale conformational searches on small modified DNA subunits, followed by energy-minimized build-up techniques, to generate atomic resolution views of these adducts. These energy-minimized duplex dodecamers were then subjected to 100-ps molecular dynamic simulations with solvent and salt to yield animated molecular structures. The most favored computed structure for the (+)-adduct places the pyrenyl moiety in the B-DNA minor groove, with its long axis directed toward the 5' end of the modified strand, and with a pronounced bend in the helix axis. In the (-)-adduct, there are 2 favored structures. One places the pyrenyl moiety in the minor groove, whereas the other positions it in the major groove; in both cases, the pyrenyl long axis is directed more toward the 3' end of the modified strand, and with much less helix axis bend. Structures with intercalation character computed for these adducts are less preferred. The favored computed structures agree with spectroscopic data on the (+)- and (-)-trans-anti-adducts, whereas recent experimental evidence suggests that cis-adducts assume intercalation-type structures. Perhaps the conformational distinctions elucidated for the (+)- and (-)-trans anti-adducts play a role in their differential tumorigenic properties in mammalian systems.
Cancer Res 1991 Jul 01
PMID:Structures of the (+)- and (-)-trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyre ne adducts to guanine-N2 in a duplex dodecamer. 190 97

We have studied adduct formation of the antineoplastic agent diaziquone (AZQ; NSC 182986) with DNA and nucleotides in vitro. The aziridine moieties of AZQ can be expected to interact covalently with DNA which, in turn, presumably elicits the antitumor activity. We analyzed AZQ-DNA adducts by a modified 32P-postlabeling assay involving purification of the nuclease P1-enriched labeled adducts by high-salt C18 reversed-phase thin-layer chromatography and separation of the eluted adducts on a polyethyleneimine-cellulose layer using non-urea salt solutions. Modification of calf thymus DNA with AZQ produced two major (22% and 40%) and at least eight minor adducts. At equal concentrations of AZQ and DNA (1 micrograms/microliters each), peak binding was observed in about 2 h [1926 +/- 378 (SD) fmol/micrograms of DNA] with the binding levels remaining practically unchanged through 4 h. However, incubation for 24 h resulted in over 40% decline, indicating adduct instability. AZQ was found to be highly reactive in vitro as evidenced by its substantial binding (49 +/- 14 fmol/micrograms of DNA) even at a DNA:AZQ ratio of 100:1. When incubated with mononucleotides, AZQ reacted extensively with adenine, guanine, and cytosine but only slightly with thymine. Cochromatography of the modified DNA and nucleotides revealed that one of the major adducts and several minor adducts were guanine derived. The aziridine rings of AZQ were found to be the main reactive sites as its monoaminoalcohol derivative showed as much DNA reactivity as did the parent compound, but no activity was observed when both aziridine groups were hydrolyzed to diaminoalcohols. The improved 32P-postlabeling assay seems capable of detecting relatively polar adducts such as those formed with AZQ at a level of one adduct/10(9) nucleotides.
Cancer Res 1991 Oct 01
PMID:DNA adducts of the antitumor agent diaziquone. 191 43

Noncommunicable diseases--cardiovascular and cerebrovascular disease, pulmonary diseases, liver disease, cancer, diabetes, osteoporosis and trauma--constitute the major cause of death in developed countries and are predictably emerging as significant threats to health in countries at intermediate stages of the epidemiological transition. Based on the philosophy that diseases with common risk factors (inadequate prevention/control services, smoking, fat/salt diet, alcohol use, etc.) require common preventive strategies, the INTERHEALTH demonstration projects are designed to build regional capacities and to exchange social and medical technologies for broad-gauged noncommunicable disease prevention and control. Projects are at various stages of planning and implementation in all WHO regions: Africa (Mauritius, United Republic of Tanzania); the Americas (Chile, Cuba, United States); Eastern Mediterranean (Cyprus); Europe (Finland, Malta, USSR); South-East Asia (Sri Lanka, Thailand); the Western Pacific (Australia, China, Fiji, Japan). This article presents selected data which illustrate the long-term mortality trends and present noncommunicable disease risk-factor levels in participating countries at different stages of the epidemiological transition. The shift towards noncommunicable diseases as a cause of death is readily apparent and combinations of risk factors are present in each of the populations studied in the baseline phase of this research and demonstration programme. The use of data to estimate the noncommunicable disease-related mortality burden from different lifestyles and risk factors is illustrated and findings from the most advanced demonstration studies are briefly outlined.
 ...
PMID:Demonstration projects for the integrated prevention and control of noncommunicable diseases (INTERHEALTH programme): epidemiological background and rationale. INTERHEALTH Sterring Committee. 192 92

Cerebrovascular diseases (CVD) claim 1.5 million lives each year in industrialized countries; in developing countries, estimates suggest the same distressing trends. CVD rank as the third leading cause of death after ischaemic heart disease and cancer. Surviving patients are left disabled and paralysed, dependent on their families and on society. Lifestyle, an issue of concern both for the individual and the community, can play an important role in the primary prevention of CVD when combined with dietary adjustments and appropriate drug therapy; it can prevent and slow down the development of atheroma, help to regulate blood pressure and contribute to the prevention of heart diseases likely to cause embolic strokes. The preventive treatment and management of other conditions, such as rheumatic heart disease, coronary artery disease with myocardial infarction and cardiac arrhythmias (embolic strokes), combined with healthy eating habits that tend to reduce the intake of saturated fats (atherosclerosis) and salt (high blood pressure) and the avoidance of smoking and alcohol (ischaemic and haemorrhagic strokes) will help to lower the incidence of mortality and morbidity due to CVD.
 ...
PMID:[Life style and prevention of cerebrovascular accidents]. 192 96

(+-)-2-[Hydroxy[tetrahydro-2-(octadecyloxy)methylfuran-2- yl]methoxyl]phosphinyloxy-N,N,N-trimethylethaniminium hydroxide, inner salt (SRI 62-834) is a tetrahydrofuran analogue of platelet activating factor (PAF) that is currently entering clinical trial. Like other ether lipids it is of interest as a membrane-active antitumor agent. Here, we have used two-color multiparameter flow cytometry to study simultaneously its effects on cell membrane permeability, intracellular pH, and cell size/structure of EMT6 mouse mammary tumor cells and HL-60 human promyelocytic leukemia cells in vitro. Concentrations as low as 1 microM up to 100 microM SRI 62-834 caused a rapid, dose-dependent increase in membrane permeability, initially towards outward efflux of the preloaded fluorescein probe bis(carboxyethyl)carboxyfluorescein (green fluorescence) and then towards influx of extracellular propidium (red fluorescence). At the same time, median cell size from light scatter was reduced with an increased coefficient of variation, and the proportion of cell debris was elevated. In vitro antitumor activity was seen over the same concentration range, as measured by tetrazolium dye reduction and cell growth curves. Neither low concentrations of PAF (50 nM) nor the potent PAF antagonist 3-[4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-f][1,2,4]tria- zolo[4,3a][1,4]diazepin-2-yl]-1-(4-morpholinyl)-1-propanone (0.5-100 microM) had any influence on the membrane effects of SRI 62-834, and at higher concentrations (1-200 microM) PAF mimicked the behavior of SRI 62-834. In addition, the PAF antagonist did not modulate the cytotoxicity of SRI 62-834 or PAF. HL-60 cells were more sensitive to SRI 62-834 than were EMT6 cells in terms of both cytotoxicity and membrane permeability. However, PAF was more potent than SRI 62-834 in causing membrane permeabilization with both cell lines, whereas PAF was less active than SRI 62-834 in cytotoxicity assays. The results support a membrane-damaging role in the cytotoxicity of SRI 62-834 but suggest that additional factors are also involved. Membrane permeabilization may be related to its reported effects on protein kinase C-dependent intracellular calcium signaling but apparently does not involve a conventional PAF receptor in HL-60 or EMT6 cells.
Cancer Res 1991 Feb 01
PMID:Multiparametric flow cytometry of the modulation of tumor cell membrane permeability by developmental antitumor ether lipid SRI 62-834 in EMT6 mouse mammary tumor and HL-60 human promyelocytic leukemia cells. 198 20


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