Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chlorpromazine (CPZ) and caffeine (CFN) enhance the cytotoxicity of nitrosoureas in conventional murine tumor systems, but this effect was not confirmed in a randomized clinical trial which compared the action of semustine (MeCCNU) against the combination of MeCCNU, CPZ, and CFN. Since differences in repair systems are known to exist between cells of human or murine origin, we have employed a human melanoma xenograft system to quantify the drug interaction. The enhancement in human melanoma cells was similar to that observed with conventional murine tumor systems. Alkaline elution studies and determination of radioactivity from labeled MeCCNU pointed to increased drug retention and fixation of DNA damage as the mechanism of enhancement. Although toxicity studies were limited to murine tissues, there was evidence of increased toxicity, especially if MeCCNU was combined with both CPZ and CFN. Thus, a true therapeutic synergism may not be present for the combination. Some explanations for the failure to detect such drug interaction in clinical trials and the relevance of advanced preclinical tumor systems are discussed.
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PMID:Enhancement of semustine-induced cytotoxicity by chlorpromazine and caffeine in a human melanoma xenograft. 375 39

The conclusion drawn in a recent paper by Minton and associates (Cancer 1983; 51:1249-1253), that caffeine and an unsaturated fat diet significantly promoted dimethylbenz(a)anthracene (DMBA)-induced breast cancer in rats, is based on fallacious statistical reasoning. Minton and associates based their conclusion on the mean latency to first tumor appearance for rats diagnosed with tumors. However, evaluation of percentages of tumor-bearing rats yields contrary results. Using data from a totally negative hypothetical two-group experiment, we demonstrate how such "conflicting" results could arise from differential intercurrent mortality in the two groups. The correct statistical analysis of this hypothetical experiment allows for differential intercurrent mortality and no conflict arises; the data of Minton and associates need to be analyzed by these methods.
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PMID:Statistical errors invalidate conclusions in "Caffeine and unsaturated fat diet significantly promotes DMBA-induced breast cancer in rats". 391 18

Studies have associated coffee and/or caffeine with human fibrocystic breast disease. Two animal studies have implicated caffeine as a promoter in rat mammary cancer. The current investigation examines the effect of two caffeine doses in ACI rats with and without diethylstilbestrol (DES). Without DES, cancer did not develop in any of the rats receiving either of the two caffeine dosages. With DES, increasing caffeine dosage lengthened the time to first cancer, decreased the number of rats that developed cancers, and decreased the number of cancers overall. The presence or amount of caffeine did not cause detectable histologic differences in the breast cancers. The presence or amount of caffeine did not influence animal weight or mortality, although the rats without DES weighed more and survived better into old age. The presence or amount of caffeine did not influence pituitary weights and prolactin levels, although values of the DES groups were three times higher than the values for the group without DES (P less than 0.05). In conclusion, chronic caffeine ingestion inhibits rat breast cancer, neither by interfering with the high prolactin levels--a necessary step in murine tumor development--nor by causing hypocaloric intake.
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PMID:The inhibitory effect of caffeine on hormone-induced rat breast cancer. 402 28

In order to gain an insight into the nature of the radiomimetic activity by which the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) alters cell cycle parameters in HeLa cells, possibilities of modifying the TPA-induced G2 block and recovery from it were studied. TPA-induced G2 blockage was analysed by counting mitotic figures. It was not influenced by hydroxyurea (10(-3) M) thus indicating that it is independent of DNA synthesis. TPA-induced decrease of mitotic activity occurred faster than that caused by cycloheximide (10(-5) M) indicating that the TPA-sensitive transition point in G2 is closer to mitosis than that for cycloheximide. Superoxide dismutase, catalase, alpha-tocopherol, the radioprotector S-(2-aminoethyl)isothiuroniumbromide.HBr (AET), caffeine and indomethacin and eicosatetraynoic acid (ETYA), both inhibitors of oxygenases in the arachidonic acid cascade, were not capable of reducing the TPA-induced G2 response. Under certain conditions small concentrations of AET (10(-8) M) and ETYA (10(-8) M) appeared to improve recovery slightly. Mannitol and sorbitol, however, both hydroxyl radical scavengers at 0.1 M concentration reduced TPA-effectiveness to a large degree (0.1 M D- and L-mannose were ineffective). Dimethylsulfoxide (0.1 M), another hydroxyl radical scavenger, was ineffective.
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PMID:Mechanistic aspects of the delay in the G2 phase of the cell cycle caused by tumor promoter 12-O-tetradecanoylphorbol-13-acetate in HeLa cells. 402 35

We demonstrated previously that the effect of cis-diamminedichloroplatinum(II) (cisplatin) against pancreatic cancer was substantially enhanced by the addition to the chemotherapeutic regimen of 1-beta-D-arabinofuranosylcytosine and caffeine. To obtain information on the factors influencing tumor response to this combination treatment, we investigated two adenocarcinomas of the exocrine pancreas grown in the nude mouse, tumors Capan-1 and SW-1990. Tumor response to cisplatin, characterized by tumor regression and tumor growth arrest, was observed when it was given in the upper limits of tolerance (5 mg/kg). Caffeine and 1-beta-D-arabinofuranosylcytosine singly and in combination had no effect on tumor growth; neither did they influence the effect of cisplatin when combined singly with the latter. However, the triple combination of cisplatin, 1-beta-D-arabinofuranosylcytosine, and caffeine resulted in complete tumor regression. The enhancing effect of the triple combination depended on tumor sensitivity to cisplatin and the amount of cisplatin administered and required rather large amounts of caffeine. The present report indicates that certain combination regimens may enhance the therapeutic effect of cisplatin against pancreatic carcinoma.
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PMID:Enhanced therapeutic effect of cis-diamminedichloroplatinum(II) against nude mouse grown human pancreatic adenocarcinoma when combined with 1-beta-D-arabinofuranosylcytosine and caffeine. 406 65

The effect of phorbol ester tumor promoters on the communication between individual cells in confluent culture was studied using a fluorescent dye transfer method. Cell-cell communication between mouse Balb/c 3T3 cells and between Chinese hamster V79 cells was inhibited almost completely by tumor-promoting phorbol esters, but not by nonpromoting derivatives; the effect was reversed upon removal of the promoter. Intercellular communication between Balb/c 3T3 cells, but not Chinese hamster V79 cells, was increased significantly in the presence of dbcAMP and caffeine, and these compounds counteracted the effects of tumor promoters. Inhibition of cell communication by phorbol esters appears to be receptor-mediated, since specific binding of 3H-phorbol-12,13-dibutyrate to Balb/c 3T3 cells was inhibited only by compounds that also inhibit intercellular dye transfer. A study with cycloheximide suggests that the reversible inhibition of intercellular communication by phorbol esters may not need de novo protein synthesis, while upregulation of communication by cAMP requires protein synthesis.
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PMID:Inhibition of cell communication between Balb/c 3T3 cells by tumor promoters and protection by cAMP. 609 91

Studies were performed to define conditions under which propagation, assay and stabilization of the Delta herpesvirus (DHV) strain of simian varicella virus might be improved, and to compare biological properties of DHV with those of human varicella zoster virus (VZV). A mycoplasma contaminant was successfully eliminated from the DHV seed virus by treatment with a specific anti-serum. DHV was found to replicate more efficiently in the BS-C-1 line of African green monkey kidney cells than in Vero cells, and seed virus preparations in the form of virus-infected cells were produced which had infectivity titers greater than or equal to 1 X 10(6) p.f.u./ml. Greater yields of virus were produced in cultures infected as dispersed cells than as preformed monolayers. Infectious DHV could be released from host cells by sonic treatment of heavily infected cultures at 48 h post infection. Certain agents reported to enhance replication of herpes viruses (caffeine, carbaryl, the tumor promoter 12-0-tetra-decanoyl-phorbol-13-acetate, and DEAE-dextran) had no enhancing effect on replication of DHV. However, DEAE-dextran in the maintenance medium enhanced spontaneous release of DHV into culture fluids. Plaquing efficiency and plaque size of DHV were greater in BS-C-1 than in Vero cells, and plaque assays and plaque reduction neutralization tests were developed in this cell system using a solid overlay medium with neutral red vital stain. Neutralization of DHV was markedly enhanced by fresh guinea pig complement. The newly developed neutralization test demonstrated more vigorous antibody responses to DHV in active and latent VZV infections than were demonstrated with previous procedures. In addition to their preferential growth in monkey and human cells respectively, DHV and VZV were found to differ markedly in their rates of attachment to host cells, with DHV requiring over 6 h of adsorption, while VZV adsorption was essentially complete at 1 h. Also, cell-free DHV was much more resistant than cell-free VZV to repeated cycles of freezing and thawing.
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PMID:Improved yields and assay of simian varicella virus, and a comparison of certain biological properties of simian and human varicella viruses. 629 81

The large tumor antigen (T antigen) is a genome regulation protein, coded by simian virus 40, that binds with high affinity to specific binding sites on viral DNA. The specifically bound T antigen is released from these sites in 0.2-0.3 M NaCl. Immunoprecipitation techniques were used to show that T antigen also dissociates in 0.2-0.3 M NaCl from mature viral chromatin but not from replicating viral chromatin. In fact, a considerable fraction of T antigen remains associated with replicating chromatin at NaCl concentrations as high as 1.2 M NaCl when most chromatin proteins, including histones, dissociate. However, T antigen binding to both replicating DNA and mature DNA is sensitive to intercalating drugs such as caffeine and ethidium bromide. We consider the possibility that the unexpectedly tight binding of T antigen to replicating DNA is related to the function that T antigen performs during viral DNA replication.
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PMID:The simian-virus-40 large-tumor antigen in replicating viral chromatin. A salt-resistant protein-DNA interaction. 630 57

Previous work has shown that the presence of a phorbol ester tumor promoter, phorbol 12-myristate 13-acetate (PMA), during a single-step selection for methotrexate (MTX)-resistant mouse 3T6 cells results in an up to 100-fold increase in the incidence of MTX-resistant, colony-forming cells. MTX resistance of most of these cells is due to amplification of the gene for dihydrofolate reductase (DHFR), the target enzyme for MTX. We show here that other active, noncytotoxic phorbol ester tumor promoters, such as phorbol 12, 13-didecanoate and 20-phorbol 12,13-butyrate, at their optimal concentrations (approximately equal to 0.1 microM) are approximately equal to PMA in increasing the incidence of MTX-resistant 3T6 colonies. Mezerein, a potent second-stage tumor promoter, but a weak complete promoter, increases the incidence of MTX resistance up to 350-fold, the strongest effect for any of the agents so far tested. PMA analogs that are inactive as tumor promoters, such as phorbol or phorbol 12,13,20-triacetate, have no effect on the incidence of MTX-resistant 3T6 colonies. Anthralin, a nonphorbol tumor promoter, is approximately equal to 40% as active as PMA in the MTX selection assay. Remarkably, the hormones insulin, arginine vasopressin, and epidermal growth factor, all of which are mitogenic for 3T6 cells, also exert a strong PMA-like effect on the incidence of MTX-resistant 3T6 colonies under conditions of MTX selection. The effect of insulin at its optimal concentration (approximately equal to 1 microgram/ml) is approximately equal to 70% that of PMA. Although the effect of PMA on the incidence of MTX-resistant 3T6 colonies does not significantly depend on the initial density of seeded cells or volume of the medium added, the analogous effect of insulin is strongly influenced by these parameters. Mevalonic acid, arachidonic acid, thymidine, caffeine, and nicotine, all of which are known to influence patterns of DNA synthesis in mammalian cells, were tested at their highest noncytotoxic concentrations and failed to produce any significant effect on the incidence of MTX-resistant 3T6 colonies. We discuss possible mechanisms of hormone- and tumor promoter-facilitated gene amplification in mammalian cells, relationship of mitogenic hormones to tumor promoters, and also implications of our findings for the problem of drug resistance in cancer chemotherapy.
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PMID:Mitogenic hormones and tumor promoters greatly increase the incidence of colony-forming cells bearing amplified dihydrofolate reductase genes. 635 Oct 57

The following study was carried out to determine the possibility of caffeine being a promoter of breast cancer development in animals consuming vegetable fat. A controlled study, comparing the time of mammary tumor development and the number of tumors was carried out in Sprague-Dawley rats which had been given 20 mg of DMBA at seven weeks of age. This study evaluated the tumor promotional effects of caffeine alone, caffeine and unsaturated fat in combination, unsaturated fat alone, and a standard rat chow diet. The results show that the rats which consumed caffeine and unsaturated fat had the earliest development of tumor and the most multiple tumor occurrence. Average time to tumor development was 95 days. The fat or standard chow rats had an average time to tumor development of 134 and 140 days, respectively. The caffeine-alone rats had a mean time to tumor development of 188 days. The combination of an unsaturated fat diet and caffeine significantly shortened the time to tumor development when compared with the other three groups.
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PMID:Caffeine and unsaturated fat diet significantly promotes DMBA-induced breast cancer in rats. 640 86


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