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

Bone marrow cells from leukemic and nonleukemic patients were examined for chromosome breakage in cultures treated with fluorodeoxyuridine (FUdR) and FUdR plus caffeine. The results indicate that the leukemic cells have more chromosome breakage than the nonleukemic cells when thymidylic synthetase is inhibited by FUdR. Addition of caffeine did not enhance this chromosome breakage. These findings of enhanced breakage by FUdR exposure in vitro, nevertheless, may suggest that leukemic cells in general are more susceptible to breakage than normal cells, thereby predisposing the former to secondary chromosome rearrangements.
Cancer Genet Cytogenet 1988 Jul 01
PMID:Chromosome breaks and fragile sites in leukemic bone marrow cells. 296 51

A high concordance has been reported between fragile sites and breakpoints involved in chromosomal rearrangements in cancer. A prospective study on the role of fragile sites in the etiology of childhood acute lymphocytic leukemia (ALL), with appropriate comparisons to results obtained from normal controls, analyzed fluorodeoxyuridine-, aphidicolin-, and caffeine-induced fragile sites in the peripheral blood of seven ALL patients (three with cytogenetically normal karyotype and four with pseudodiploid karyotype) and eight normal controls. While extensive variations in the number and distribution of fragile sites was observed within each group, there was no significant difference in the mean total fragile sites and mean fragile sites per cell between the two groups (P greater than 0.05) in all three treatments. Similarly, within the ALL patients, the two karyotypic groups did not exhibit any significant difference in fragility (P greater than 0.05).
 ...
PMID:Expression of fragile sites in childhood acute lymphoblastic leukemia patients and normal controls. 297 Apr 24

Effects of compounds that inhibit repair of DNA lesions in cells have been reported frequently. The consequences include altered incidence of carcinogenicity in vivo, tumorigenic transformation of cultured cells, mutations, and increased lethality as well as sister-chromatid exchanges and chromosome aberrations. This literature is reviewed here, with major emphasis on methylxanthines (caffeine in particular) and nicotinamide analogs. Existing information is also summarized on a novel potent repair inhibitor, beta-lapachone. Compounds that inhibit both DNA replication and repair are not discussed in detail since they have been reviewed often, but miscellaneous inhibitors of repair are summarized in a table. The relatively small number of experiments performed on the anticarcinogenic effects of methyl-xanthines and nicotinamide analogs gave very conflicting results. Some investigators report decreased carcinogenicity of DNA-damaging agents when caffeine was provided, but others obtained the opposite effect. The three studies with nicotinamide analogs all reported enhanced tumorigenicity of carcinogens. The data are too few to enable firm conclusions to be drawn regarding the possibility of using repair inhibitors to prevent cancer in humans. Variations of experimental conditions, carcinogens, cells, etc. have provided conflicting results. The possibility of cancer prevention is, nevertheless, so important that further investigations with DNA-repair inhibitors, particularly with human cells, seem very well justified.
 ...
PMID:Anticarcinogenic potential of DNA-repair modulators. 297 63

The phosphodiesterase inhibitors caffeine, theophylline, aminophylline and isobutyl-methylxanthine (IBMX) were found to inhibit induction of morphologically transformed hamster embryo cell colonies by sequential exposure to benzo[a]pyrene (BaP) and the tumor promoter TPA. Almost complete inhibition of cell transformation was observed when 50 micrograms/ml theophylline, aminophylline, IBMX, or 200 micrograms/ml caffeine was present together with the tumor promoter. The compounds had no effect on the transformation frequency when present together with the initiator, BaP, in the first exposure period. Substances that stimulate the adenylate cyclase and the addition of exogenous dibutyryl-cAMP had similar inhibitory effects.
Cancer Lett 1985 Aug
PMID:Caffeine and other phosphodiesterase inhibitors are potent inhibitors of the promotional effect of TPA on morphological transformation of hamster embryo cells. 299 64

The antitumor antibiotic neocarzinostatin (NCS), which produces single-strand breaks in mammalian cell DNA in vivo, stimulated the activity of chromatin bound enzyme, poly(ADP-ribose) polymerase in HeLa-S3 cells. Because of the possible causal relationship between the poly ADP-ribosylation of chromatin protein and NCS-induced temporary G2 arrest in the cell cycle, several classes of inhibitors of poly(ADP-ribose) polymerase were examined to evaluate the effect on NCS-induced polymerase activity as well as on progression in the cell cycle of synchronized HeLa cells which had been treated with NCS in G2. Compared at the same concentration of 2 mM, the polymerase-inhibiting activity was larger in the order of thymidine, 3-aminobenzamide, nicotinamide, theophylline, and caffeine. Among these agents, caffeine, theophylline, and thymidine caused a reduction in the G2 delay in this order by stimulating the cells to undergo mitosis after NCS treatment. However, 3-aminobenzamide and nicotinamide were poor reducers, if any, of NCS-induced G2 delay. These results suggest that there is not a direct involvement of poly ADP-ribosylation of chromatin protein in the mechanism of NCS-induced G2 delay. The effect of caffeine on G2 delay will probably be independent of its activity as a poly(ADP-ribose) polymerase inhibitor.
Cancer Res 1985 Sep
PMID:Effect of poly(adenosine diphosphate-ribose) polymerase inhibitors on neocarzinostatin-induced G2 delay in HeLa-S3 cells. 299 74

In an effort to understand the mechanism of action of the DNA-intercalating antitumor agent 9-hydroxyellipticine (9-OH-E), we have examined the effects of this drug on the cell survival, macromolecular syntheses, and cell cycle progression in sensitive and resistant cells. Our results show that 9-OH-E toxicity on sensitive and resistant cells involves different mechanisms of action: the drug toxicity in the sensitive cells appears to result from lethal lesions mediated through the interaction of the drug with an intracellular protein, independently of any effect of the drug on the macromolecular syntheses; in the resistant cells, the cell death occurs concomitantly with the inhibition of these syntheses. Cell cycle progression analysis after 9-OH-E treatment showed that, in the sensitive cells, the drug is inducing a G1 and a G2 block, which are both released in the presence of 1 mM caffeine, without any effect on the 9-OH-E toxicity. In the resistant cells, a G2 block was also observed but only when the cells were resuming their growth after about a 30- to 40-h growth arrest. Caffeine release of this block, which again had no effect on 9-OH-E toxicity, was only observed when it was added from 40 to 60 h after 9-OH-E treatment, when the cells resumed their growth. Finally in the sensitive cells, cycloheximide exerted an inhibitory effect on 9-OH-E toxicity when it was added before and during the cell exposure to the drug. This effect was interpreted as indicating that 9-OH-E toxicity in the sensitive cells relies on a protein which is not induced by the drug but has to be present in the cells when the drug is added. The possible implication of DNA topoisomerases in 9-OH-E toxicity mechanism is discussed.
Cancer Res 1985 Sep
PMID:Effects of 9-OH-ellipticine on cell survival, macromolecular syntheses, and cell cycle progression in sensitive and resistant Chinese hamster lung cells. 299 75

Experiments were performed to determine whether the expression and/or repair of potentially lethal damage could be observed in mammalian cells exposed to hemataporphyrin derivative (HPD) photodynamic therapy (PDT). Photodynamic therapy was combined with posttreatment protocols known to inhibit the repair of potentially lethal damage in cells treated with X-rays, ultraviolet radiation, or alkylating agents. Potentiation of lethal damage from photodynamic therapy was induced by hypothermia (4 degrees C) following short (1 h) or extended (16 h) HPD incubation conditions. Caffeine potentiated the lethal effects of PDT only when cells were incubated with HPD for extended time periods. However, 3-aminobenzamide had no effect on the cytotoxic actions of PDT following either short or extended HPD incubations. Recovery from potentially lethal damage expressed by posttreatment hypothermia was complete within 1 h, while recovery from potentially lethal damage expressed by posttreatment caffeine required time periods of up to 24 h. The lack of effect of 3-aminobenzamide on expression of potentially lethal damage following photodynamic therapy may be related to direct inhibition of adenosine diphosphoribose transferase by photodynamic therapy. These results indicate that the expression and repair of potentially lethal damage can be observed in cells treated with PDT and will vary as a function of porphyrin incubation conditions.
Cancer Res 1986 Jul
PMID:Expression of potentially lethal damage in Chinese hamster cells exposed to hematoporphyrin derivative photodynamic therapy. 301 Dec 47

The various risk factors for breast cancer have been recognized for many years. A table lists these established breast cancer risk factors together with the approximate magnitude of the increase in risk associated with them. Breast cancer incidence rates increase with age throughout the life span in Western countries, although the rate of increase is greater up to age 50 years than after 50 years. Breast cancer is more common among women in upper rather than lower social classes, among women who never have been married, among women living in urban areas, among women living in the northern US than in the southern US, and among whites than blacks, at least among those over age 50. Women in North American and Northern European countries have the highest risk for breast cancer, women in Southern European and Latin American countries are at intermediate risk, and women in Africa and Asian countries have the lowest risk. Yet, rapid rates of increase in incident rates have been noted in recent years in many Asian, Central European, and some South American countries. The later the age at which a woman has her 1st full-term pregnancy, the higher her risk for breast cancer; the earlier the age at menarche and the later the age at menopause the higher the risk; and among women who have a premenopausal oophorectomy, the earlier the age at which this occurs the lower the risk. Among postmenopausal women, obesity is associated with an increase in risk. Lactation is negatively associated with subsequent breast cancer risk. Some current research is considering potential risk factors that have not been well studied in the past, including alcohol consumption, cigarette smoking, caffeine consumption, exposure to diethylstilbestrol (DES), emotional stress, exposure to electric power, and lack of physical activity. Other areas of current research reviewed here include radiation, mammographic parenchymal patterns, a high-fat diet, use of oral contraceptives (OCs), use of estrogen replacement therapy, and endogenous hormones. Cigarette smoking and caffeine consumption do not appear promising as potential etiologic agents. The studies of the DES-exposed women and of OC users suggest that the timing of exposure may be critical, since the possible effect of both these hormonal agents may be limited to specific time periods of rapid breast development. If such a critical period does not exist in postmenopausal women, then there may be little effect of hormones used at this time. Studies with long-term follow-up and that include long-term users are essential to studies of effects of hormones and other exposures.
Cancer Res 1988 Oct 15
PMID:Breast cancer epidemiology. 304 46

Caffeine is ubiquitous in our environment and is the most widely used psychoactive drug in the world. Caffeine works on every system in the body mediated by the central nervous system. Caffeine has the opposite effect of adenosine and is the antagonist at the inhibitory A1-receptor. Caffeine elevates the free fatty acid mobilization and could enhance weight loss through pre-exercise caffeine ingestion. However, this hypothesis remains to be proven until an increase in fat oxidation is found. Caffeine is metabolized to more than 25 metabolites in man. Less than 5% of the caffeine is found in the urine as unchanged drug. The half-life of caffeine ranges from 1.5 to 9.5 hours. Smoking decreases the half-life of caffeine. Caffeine is used for the treatment of apnea of prematurity and as an additive in several analgesics and migraine remedies, and as a panacea for hyperkinetic children. Although much work has been done to establish the relationship between caffeine and cancer and mutagenicity, none of these have established a cause-effect relationship. The consumption of caffeine products in moderation appears to be safe at this point.
 ...
PMID:Caffeine: a new look at an age-old drug. 307 3

Human tumor cells, like rodent cells, are sensitive to effects of methylxanthines (MEX) on lethality, cell cycle delays, and chromosome aberrations after DNA damage by anticancer drugs. Enhanced cytotoxicity of alkylating agents was observed when T24 human bladder tumor cells in culture were exposed to nontoxic concentrations of MEX such as caffeine or pentoxifylline. Tumor cell lethality was increased up to 10-fold by either caffeine or pentoxifylline (1 mM) present during the first cell cycle (16-24 h) after exposure to nitrogen mustard (HN2) or thiotepa. Cycloheximide, a protein synthesis inhibitor, abolished the enhanced lethality produced by MEX. In these synchronized human tumor cells further kinetic studies revealed that HN2 (0.5 microM X 1 h) delayed transit through S phase by about 1-2 h, and this delay was prevented by MEX. After completion of S phase, HN2-treated cells were delayed 3-6 h in G2, and MEX also prevented this delay, leading to mitoses at the rate of controls. Chromosome analysis of these mitotic cells revealed dramatic increases in aberrations induced by alkylator + MEX combinations. The greatest number of aberrations was seen in HN2-treated cells exposed briefly to MEX in late S-G2. In contrast, no increased chromosome damage was seen in cells exposed to MEX in mid-S phase. Taken together, our results are consistent with the model that MEX enhance lethality of alkylator-treated human tumor cells by preventing delays in cell cycle transit through G2, leading to chromosome aberrations which are lethal. G2 delays in human tumor cells may provide time for repair processes that are critical for survival after sublethal DNA damage by HN2 or other anticancer alkylating agents.
Cancer Res 1986 May
PMID:Cytotoxic, cell cycle, and chromosomal effects of methylxanthines in human tumor cells treated with alkylating agents. 308 68


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>