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)

In RBL-2H3 rat basophilic leukemia cells, cholera toxin does not per se stimulate secretion but it enhances secretion stimulated by antigens that crosslink IgE receptors, by the Ca2+ ionophore, ionomycin, and by thapsigargin, a tumor promoter that releases cytoplasmic Ca2+ stores. Calmodulin inhibitors reduce both the basal and cholera toxin-enhanced secretory responses to antigen and Ca2(+)-mobilizing agents. These synergistic effects suggest that the activation of a Gs-like GTP-binding protein, together with a (probably calmodulin-dependent) event activated by an increase in cytoplasmic Ca2+ levels, may jointly provide a sufficient signal for secretion. Antigen-stimulated secretion is inhibited by depleting cells of GTP with mycophenolic acid but is maximal in cells treated with mycophenolic acid plus cholera toxin. The simplest explanation is that cholera toxin selectively reactivates the Gs-coupled pathway leading to secretion in GTP-depleted cells without restoring the activity of a separate GTP-binding protein(s) that constrains antigen-stimulated secretion.
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PMID:Regulation of IgE receptor-mediated secretion from RBL-2H3 mast cells by GTP binding-proteins and calcium. 182 63

Our recent studies have shown that polyphenols present in green tea (GTP) possess significant antigenotoxic activity and afford protection against polycyclic aromatic hydrocarbon-induced skin tumor initiation in mice. In this study we assessed the effect of oral feeding and topical application of GTP on ultraviolet B (UVB) radiation-induced skin carcinogenesis in female SKH-1 hairless mice. Chronic oral feeding of GTP (0.1%, w/v) in drinking water resulted in significantly (P less than 0.01) lower tumor yield (percent of animals with tumors and number of tumors per mouse) and extended TDT50 (P less than 0.05), as compared to animals receiving normal drinking water. Topical application of GTP before UVB irradiation also afforded protection against photocarcinogenesis; however, the protective response was lower than that observed by oral feeding of GTP in drinking water. These results, in conjunction with our prior publications, suggest that consumption of green tea may reduce the risk of some forms of human cancer induced by both physical and chemical environmental carcinogens.
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PMID:Protection against ultraviolet B radiation-induced photocarcinogenesis in hairless mice by green tea polyphenols. 186 Jan 73

Data generated in the new National Cancer Institute drug evaluation program, which is based on inhibition of cell growth in 60 human tumor cell lines, were used to compare new compounds with agents of known mechanism of action in terms of their differential cytotoxicity. Two marine natural products, halichondrin B and homohalichondrin B, appeared repeatedly when the data base was probed with known antimitotic agents. We confirmed that both compounds were highly cytotoxic (IC50 values for L1210 murine leukemia cells of 0.3 and 1 nM, respectively), with accumulation of cells arrested in mitosis at toxic concentrations, that both inhibited the polymerization of purified tubulin, and that both inhibited microtubule assembly dependent on microtubule-associated proteins. Limited amounts of homohalichondrin B, the less active agent, were available, so only halichondrin B was studied in detail. Halichondrin B did not interfere with colchicine binding to tubulin, but it was a noncompetitive inhibitor of the binding of vinblastine to tubulin (apparent Ki, 5.0 microM). Halichondrin B was therefore compared with other agents which interfere with the binding of vinca alkaloids to tubulin (vinblastine, maytansine, dolastatin 10, phomopsin A, rhizoxin) in terms of its effects on tubulin polymerization, inhibition of GTP hydrolysis, inhibition of nucleotide exchange, and stabilization of tubulin, as well as the quantitative assessment of its effects on vinca alkaloid binding and inhibition of cell growth. Since halichondrin B was originally isolated from the same organism as the phosphatase inhibitor okadaic acid, and since it is about 50-fold more effective than okadaic acid as an inhibitor of L1210 cell growth, perturbations of cellular microtubules observed following treatment with okadaic acid should be interpreted cautiously.
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PMID:Halichondrin B and homohalichondrin B, marine natural products binding in the vinca domain of tubulin. Discovery of tubulin-based mechanism of action by analysis of differential cytotoxicity data. 187 39

A 30-residue peptide corresponding to the amino acid sequence of steroidogenesis activator peptide (SAP) from rat Leydig tumor cells has been synthesized by the solid-phase method using Boc protection. SAP is the putative cycloheximide-sensitive, cAMP-regulated mediator of ACTH-stimulated conversion of cholesterol to pregnenolone in adrenal cortex. N alpha-acetyl-SAP(11-30), an NH2-terminally truncated steroidogenesis activator peptide analog that is missing the most hydrophobic portion of SAP, was also prepared. In addition to these two peptides, N alpha-acetyl-(Cys0)SAP was synthesized in both non-radiolabeled and tritiated forms for coupling to carrier proteins for use as an immunogen to raise anti-SAP antibodies. Chain elongation during synthesis of SAP on PAM resin proceeded with an average coupling yield of 99.3% as determined by quantitative ninhydrin tests. After HF cleavage at -7 degrees, the crude products were purified by semi-preparative HPLC. Peptides were analyzed by analytical HPLC, amino acid analysis, tryptic peptide mapping, and by UV and CD spectroscopy. As determined by CD spectra, SAP showed little evidence of preferred structure either in aqueous solution in the presence of divalent cations or in micelles of reduced Triton X-100 in the absence or presence of either cholesterol or phosphatidylcholine. SAP, in conjunction with GTP, enhanced side chain cleavage activity in isolated adrenal mitochondria.
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PMID:Chemical synthesis, initial conformational studies, and activity of rat steroidogenesis activator peptide and a truncated analog. 187 80

Interferons have been shown to be potential anti-cancer agents and to inhibit tumor cell growth in culture. The in vivo mechanism of the anti-proliferative effect may be direct or indirect through the immune system; however, in vitro a primary mechanism of cytotoxicity is through the depletion of tryptophan. In particular, interferon-gamma (IFN-gamma) induces an enzyme of tryptophan catabolism, indoleamine 2,3-dioxygenase (IDO), which is responsible for conversion of tryptophan and other indole derivatives to kynurenine. The inhibitory effect of interferon on many intracellular parasites such as Toxoplasma gondii and Chlamydia trachomatis is by the same mechanism. Elevated kynurenine levels have been found in humans in a number of diseases and after interferon treatment, and the enzyme is induced in rodents after administration of interferon inducers, or influenza virus. IDO induction also occurs in vivo during rejection of allogeneic tumors, indicating a possible role for this enzyme in the tumor rejection process. The gene for IDO has been cloned and shown to be differentially regulated by IFN-alpha and IFN-gamma. IDO induction has been correlated with induction of GTP-cyclohydrolase, the key enzyme in pteridine biosynthesis. A direct role for IDO in pteridine synthesis has not been shown, and this parallel induction may reflect coordinate regulation of genes induced by IFN-gamma. A possible role for IDO in O2-radical scavenging and in inflammation is discussed.
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PMID:Relationship between interferon-gamma, indoleamine 2,3-dioxygenase, and tryptophan catabolism. 175 66

To identify new DNA markers around the neurofibromatosis-2 gene on human chromosome 22, the critical region (22q12-q13.1) was microdissected and microcloned from GTG-banded metaphase chromosomes. Eighteen thousand recombinant clones were obtained. Twenty-seven of 55 clones tested (50%) detected single-copy DNA sequences. Nine of nine clones analyzed in detail were found to map to chromosome 22. Interestingly one clone (EAN04) is part of the leukemia inhibitory factor gene which has previously been mapped to 22q11.2-q13.1. Four clones (EAN01, EAN47, EAN57, and EAN68) detect DNA polymorphisms. These probes were used to compare constitutional and tumor genotypes of 41 patients with acoustic neurinoma. Loss of constitutional heterozygosity was identified in 17 of 31 informative cases (55%). From our data we conclude that the microdissection library is a valuable resource for physical and genetic mapping studies in neurofibromatosis-2.
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PMID:New markers for the neurofibromatosis-2 region generated by microdissection of chromosome 22. 190 84

The neurofibromatosis type 1 (NF1) gene has been localized to the pericentromeric region of the long arm of chromosome 17. A chronology of events leading to the cloning of the NF1 gene is offered as a summary of modern gene hunting techniques. The gene was identified by its location rather than its function using positional cloning. Linkage analysis, based on DNA polymorphisms, is already available for prenatal and presymptomatic testing. This technique works only in cases when affected family members are available and is useless in spontaneous cases. The complete NF1 gene is huge, has a large number of exons, and is approximately 240,000 base pairs long. Its large size is consistent with the very high spontaneous mutation rate. The NF1 gene is evolutionarily conserved and expressed ubiquitously, not just in neural crest derivatives. Functional and structural homology with GAP (GTP [guanosine triphosphate]ase-activating protein) has been described. The GAP controls (or is controlled by) the ras oncogene. Aberration of ras function, which plays a fundamental role in growth, development, and differentiation, may play a role in the NF1 phenotype. Direct DNA diagnosis of mutations in the NF1 gene in clinical practice is premature. Current data suggest that the NF1 gene product may act as a tumor suppressor.
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PMID:The hunt for the neurofibromatosis gene. 195 78

The effects of Na+, K+, Mg2+ and Ca2+ on the agonist binding sites of D2 dopamine (DA) receptors were studied in 7315a pituitary tumors. The agonist high and low affinity states of the D2 receptors were investigated with apomorphine competition for [3H]spiperone binding at 25 degrees. In the tumor, all cations markedly increased the affinity of the high affinity binding site, while the affinity of the low affinity binding site was increased only by Na+. The proportion of high to low affinity states was not affected significantly by K+ and Ca2+, whereas it was decreased by Na+ and increased by Mg2+; none of these cations affected the total density of the D2 receptors. The in vitro regulation of D2 receptors by 17 beta-estradiol (E2) was next studied in 7315a tumors and bovine intact adenohypophysis. In intact anterior pituitary, a partial conversion of the high to the low affinity state was obtained in the presence of GTP, while in tumoral pituitary, a complete conversion was observed. Addition of 1 nM E2 to the in vitro incubation mixture prevented these conversions and resulted in a partial return of the high affinity state of the D2 receptors to their control values in both normal and tumoral pituitary. In another experiment, using increasing concentrations of E2 (0.01 to 100 nM) and GTP (10(-8) to 10(-3) nM) on [3H]n-propylnorapomorphine [( 3H]NPA) binding to the D2 receptors in bovine intact adenohypophysis, 1 and 10 nM E2 doubled the IC50 of GTP to decrease [3H]NPA binding. The results show that agonist high and low affinity states of D2 receptors in 7315a tumors are regulated normally by cations. In addition, E2 inhibited the effect of GTP on the agonist sites of the D2 receptors in both intact anterior pituitary tissue and 7315a tumors.
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PMID:Modulation of dopamine receptor agonist binding sites by cations and estradiol in intact pituitary and 7315a tumors. 195 34

IMP dehydrogenase (EC 1.1.1.205), the rate-limiting enzyme of de novo GTP biosynthesis, is a promising target in antileukemic chemotherapy. We have isolated two distinct cDNA clones (types I and II) encoding IMP dehydrogenase from a human spleen cDNA library. Both clones encode closely related proteins of 514 residues showing 84% sequence identity. Northern hybridization analyses of poly(A)+ RNA from human normal leukocytes and human ovarian tumors demonstrated a striking contrast in mRNA expression in that type I mRNA is the main species in normal leukocytes and type II predominates over type I in the tumor. This is the first report suggesting the existence of two distinct types of human IMP dehydrogenase molecular species which may have different sensitivities to the drugs targeted against IMP dehydrogenase.
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PMID:Two distinct cDNAs for human IMP dehydrogenase. 196 16

gamma-Glutamyl transpeptidase (gamma-GTP) has been noticed as one of the useful markers for malignant transformation of the skin. But the role and mechanism of the induction of gamma-GTP in skin carcinogenesis had not yet been studied. In this report, the authors studied the relationship between gamma-GTP activity and tumor differentiation in squamous cell carcinoma of human skin (SCC). Ten cases of SCC were examined on intensity and localization of the activity of gamma-GTP histochemically by the method of Rutenberg. gamma-GTP activity was found to be more intense in well differentiated SCC than in poorly differentiated SCC. On the other hand, localization pattern of gamma-GTP activity in SCC was not always related to the tumor grade. We concluded that expression of gamma-GTP activity in SCC may reflects the modulating cell differentiation rather than cell proliferation in malignant transformation of the skin. And some of the typical cases were presented.
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PMID:[Expression of gamma-glutamyl transpeptidase related to the tumor differentiation on squamous cell carcinoma of human skin]. 197 39


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