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

The distribution of carrier-free 203Pb-acetate, 203HgCl2, 57 CoCl2, 137CsCl and 201TlCl was investigated in rats bearing thigh-implanted Morris 7777 hepatomas. Viable and nonviable tumor tissue was collected in order to determine the relative affinities of the radiopharmaceuticals for these tissues. The animals were sacrificed at 4, 24, 48, 72 and 96 hrs following intravenous injection. Washout of the radioisotope from the viable tumor tissue was rapid, the maximum concentration being reached on or before 4 hrs following injection. In contrast, residual activity within the nonviable tumor tissue decreased much more slowly and in some cases even increased with time. Viable tumor-to-muscle and nonviable tumor-to-muscle ratios for 203Pb, 203Hg and 57Co were comparable to the analogous ratios reported for 67Ga. However, none of these isotopes approached 67Ga as a potential tumor imaging agent because the large ratios were the result of low muscle uptake rather than high tumor uptake. Blood clearance of 67Ga was faster than any of the five cations, while viable and nonviable tumor affinity for 67Ga was greater than for any of the radiopharmaceuticals studied.
 ...
PMID:Distributions of 137Cs, 201Tl, 203Hg, 203Pb and 57Co in a rat hepatoma model. Comparison with 67Ga. 20 98

A comparison of the intracellular DNA strand scission activities of the antitumor drug bleomycin, three of its metal complexes, demethyl bleomycin A2, and iron-containing, redox-inactivated bleomycin in Ehrlich ascites tumor cells was performed by means of the alkaline elution technique. This comparison was aided by use of CoCl2 to eliminate or minimize post-cell lysis strand scission by bleomycin in aliquots of treated cultures. No strand scission resulted from treatment of cells with the cobalt complex. The levels of intracellular DNA degradation by copper bleomycin and iron bleomycin were equivalent to those produced by metal-free bleomycin. The findings are correlated with previous measurements of growth inhibition by these three bleomycins as well as by cobalt bleomycin and related to the concentrations of radiolabeled bleomycin bound to DNA after treatment of cells with each form of drug. In comparison, both demethyl bleomycin A2 and iron-containing, redox-inactivated bleomycin showed marked, concentration-dependent reductions in random DNA strand scission, as compared with unmodified bleomycin or iron bleomycin prepared from Fe(III) and bleomycin. However, the fraction of DNA from cells treated with these two bleomycins, which eluted through filters prior to alkaline denaturation, was equivalent to that for unmodified bleomycin and Fe(III)bleomycin. The generation of this class of damaged DNA correlates more closely with concentration-dependent growth inhibition by each of the six forms of bleomycin than the degree of random strand scission.
 ...
PMID:Intracellular DNA strand scission and growth inhibition of Ehrlich ascites tumor cells by bleomycins. 169 48

The insect growth regulator diflubenzuron (DFB), which also inhibits growth of experimental tumors in mice, was studied to determine the influence of in vivo microsomal metabolism on its antitumor activity. DFB inhibits chitin synthesis and growth of imaginal epidermis in insects and suppresses melanogenesis and uptake of nucleosides in mouse melanoma cells, but the means of cell growth regulation and the role of metabolism of DFB in such regulation have not been established. Five daily injections of DFB (total of 4000 mg/kg) into C57BL/6 mice with B16 melanomas induced an acute 11-20% decrease in tumor volume and a 2-3 day increase in the initial tumor volume doubling time (Td), but at mid-treatment tumors regained maximum (control-like) rate of volume increase. Tumors in mice conditioned with a mixed function oxidase inhibitor (CoCl2) and treated with DFB did not decrease in mean volume, but their rate of volume increase was reduced by about 75% and the Td was increased by 4.2 days. In contrast, induction of mixed function oxidase with 3-methylcholanthrene (3-MC) or beta-napthaflavone (B-NF) enhanced the effects of DFB by a factor of 1.5 to 2.0. Therefore, aromatic hydroxylation of DFB may be required for tumor growth regulation. Three metabolites of DFB--two hydroxylated forms and a scission product, 4-chlorophenylurea (CPU), were also tested for tumor growth regulation. CPU was ineffective; a form oxidized at the 3 carbon of the phenyl ring (3-OH-DFB) was only marginally effective; but the 2-carbon form (2-OH-DFB) induced a 24% decrease in mean tumor volume and a 2.4 day increase in Td. Pretreatment with 3-MC and treatment with 2-OH-DFB also resulted in a 24% decrease in tumor volume and a 2.2 day increase in Td, but also reduced tumor volume increase to 20% between the 5th and 10th days after the initial 2-OH-DFB injection, compared to a 125% increase without 3-MC. Further, 3-MC pretreatment caused the otherwise marginally effective 3-OH-DFB to become almost as effective as 2-OH-DFB. These data support our previous report that DFB alters tumor growth and show that mixed function oxidase enhances effects of DFB, 2-OH-DFB and 3-OH-DFB.
 ...
PMID:Role of metabolism in effects of diflubenzuron on growth of B16 melanomas in mice. 310 86

Various modulation factors for the cytotoxic action of epigallocatechin gallate (EGCG) against two human oral tumor cell lines (HSC-2, HSG) were investigated. Three anticancer drugs (tamoxifen, sulindac, doxorubicin), two metals (CuCl2, FeCl3) and two antioxidants (sodium ascorbate, tiopronin) did not significantly affect the cytotoxic activity of EGCG, Catalase and N-acetyl-L-cysteine only marginally reduced the cytotoxic activity of EGCG. On the other hand, CoCl2 significantly protected the cell injury induced by EGCG. This suggests that the site of EGCG action might be intracellular rather than extracellular. Possible involvement of the expression of transcription factor (s) for EGCG-induced cytotoxicity is discussed.
 ...
PMID:Effect of anticancer drugs, metals and antioxidants on cytotoxic activity of epigallocatechin gallate. 1062 98

Epigallocatechin gallate (EGCG) induced apoptotic cell death in two human oral tumor cell lines (HSC-2, HSG), as judged by TUNEL method which detects DNA nick. Furthermore, the cytoplasm of EGCG-treated HSG cells was stained by M30 monoclonal antibody, which detects the degradation product of cytokeratin by activated caspase. The apoptosis-inducing activity of EGCG was significantly reduced by millimolar concentrations of CoCl2. CoCl2 also inhibited the cytotoxic activity of sodium ascorbate, gallic acid and curcumin, but not that of sodium-5, 6-benzylidene-L-ascorbate (SBA). This suggests that SBA, an antitumor agent, induces cell death by a different mechanism from that of other antioxidants used in this study. The possible role of CoCl2 for cell survival was discussed.
 ...
PMID:Inhibition of epigallocatechin gallate-induced apoptosis by CoCl2 in human oral tumor cell lines. 1069 34

Dopamine dose-dependently reduced the viable cell number of both human salivary gland tumor HSG and oral squamous cell carcinoma HSC-2, HSC-4, and NA cells. CoCl2 significantly reduced both the cytotoxic activity and radical intensity of dopamine (determined by ESR spectroscopy). Dopamine produced DNA fragments (demonstrated by TUNEL method) and induced degradation of cytokeratin by activated caspase in HSG cells (detected by an immunocytochemical method, using a specific M30 monoclonal antibody). FACS analysis demonstrated that dopamine induced DNA fragmentation, a biochemical hallmark of apoptosis, in human promyelocytic leukemia HL-60 cells. The addition of catalase did not prevent the apoptosis-inducing activity of dopamine, reducing the possibility of the involvement of H2O2 for dopamine-induced apoptosis. Dopamine transiently induced p38 mitogen-activated protein kinase (MAP kinase) phosphorylation. However, an inhibitor of p38 MAP kinase phosphorylation, SB203680, failed to inhibit the dopamine-induced apoptosis. These data suggest that p38 phosphorylation at an early stage may not be a causative event for apoptosis.
 ...
PMID:Induction of apoptosis by dopamine in human oral tumor cell lines. 1076 62

Little is known about the molecular mechanisms that control adrenomedullin (AM) production in human cancers. We demonstrate here that the expression of AM mRNA in a variety of human tumor cell lines is highly induced in a time-dependent manner by reduced oxygen tension (1% O2) or exposure to hypoxia mimetics such as desferrioxamine mesylate (DFX) or CoCl2. This AM expression seems to be under hypoxia-inducible factor-1 (HIF-1) transcriptional regulation, since HIF-1alpha and HIF-1beta knockout mouse cell lines had an ablated or greatly reduced hypoxia AM mRNA induction. Similarly, inhibition or enhancement of HIF-1 activity in human tumor cells showed an analogous modulation of AM mRNA. Under hypoxic conditions, immunohistochemical analysis of tumor cell lines revealed elevated levels of AM and HIF-1alpha as compared with normoxia, and we also found an increase of immunoreactive AM in the conditioned medium of tumor cells analyzed by RIA. AM mRNA stabilization was shown to be partially responsible for the hypoxic up-regulated expression of AM. In addition, we have identified several putative hypoxia response elements (HREs) in the human AM gene, and reporter studies with selected HREs were capable of enhancing luciferase expression after exposure to DFX. Furthermore, transient coexpression of HIF-1alpha resulted in an augmented transactivation of the reporter gene after DFX treatment. Given that most solid human tumors have focal hypoxic areas and that AM functions as a mitogen, angiogenic factor, and apoptosis-survival factor, our findings implicate the HIF-1/AM link as a possible promotion mechanism of carcinogenesis.
 ...
PMID:Hypoxia-inducible factor-1 (HIF-1) up-regulates adrenomedullin expression in human tumor cell lines during oxygen deprivation: a possible promotion mechanism of carcinogenesis. 1084 87

The effect of CoCl2 on the cytotoxic activity of various antioxidants against human oral tumor cell lines (HSC-2, HSG) and normal human gingival fibroblasts (HGF) was investigated. Noncytotoxic concentrations of CoCl2 significantly reduced the cytotoxic activity of sodium ascorbate, gallic acid, epigallocatechin gallate (EGCG), curcumin and dopamine, but not that of sodium 5,6-benzylidene-L-ascorbate (SBA) and benzaldehyde. Among these compounds, benzaldehyde showed the most prominent tumor-specific cytotoxic action. ESR spectroscopy showed that these antioxidants produced radicals under alkaline condition and that their radical intensity was transiently enhanced and finally disappeared by addition of CoCl2. Antioxidants which are sensitive to CoCl2 generally had higher cytotoxic activity and oxidation potential (measured by NO monitor) and addition of CoCl2 significantly reduced their oxidation potential. The present study suggests that cobalt ion stimulates the oxidation of antioxidants to their inactive products.
 ...
PMID:Effect of cobalt ion on radical intensity and cytotoxic activity of antioxidants. 1106 35

Millimolar concentrations of chlorogenic acid (CGA) showed higher cytotoxic activity against human oral squamous cell carcinoma (HSC-2) and salivary gland tumor (HSG) cell lines, as compared with that against human gingival fibroblast (HGF). The cytotoxic activity of CGA was significantly reduced by catalase or CoCl2, but not affected by FeCl3 or CuCl2. ESR spectroscopy showed that higher (millimolar) concentrations of CGA produced radicals under alkaline conditions, acting as a prooxidant, whereas lower concentrations of CGA scavenged superoxide and hydroxyl radical. CGA produced large DNA fragments (as identified by slightly faster migrating band of DNA on agarose gel electrophoresis) and nuclear condensation (as demonstrated by Hoechst (No. 33258) staining) in tumor cell lines. Activation of caspase was demonstrated by staining with M30 monoclonal antibody, which reacts with degradation products of cytokeratin 18. Contact with CGA for at least 6 h was necessary for irreversible cytotoxicity induction. Pretreatment of the cells with caspase 3 inhibitor partially inhibited the cytotoxic action of CGA. These date suggest that CGA induces cytotoxicity in oral tumor cell lines, possibly by hydrogen peroxide-mediated oxidation mechanism.
 ...
PMID:Induction of cytotoxicity by chlorogenic acid in human oral tumor cell lines. 1119 77

A total of 24 benzoylimidazoles and structurally-related compounds were investigated for their cytotoxic activity against oral tumor cells and normal gingival fibroblast. Compound 23 (5-(2-hydroxylbenzoyl)-2-phenylimidazole) showed the highest cytotoxic activity against both human oral tumor cell lines (human squamous cell carcinoma HSC-2, human salivary gland tumor HSG) and normal human gingival fibroblast (HGF). Compounds 7 (2-(2-hydroxybenzoyl)benz imidazo[2,1-b]thiazole), 14 (1,3-diethyl-5-(2-hydroxybenzoyl)-4-imidazoline-2-thione) and 18 (5-(2-hydroxy-4-methoxybenzoyl)-3-methyl-2-methylimino-4-thiazoline) showed slightly lower cytotoxic activity, but higher tumor-specific cytotoxic action. The cytotoxic activity of compound 23 was significantly reduced by CuCl2, but not by CoCl2, FeCl3, or by antioxidants (N-acetyl-L-cysteine, sodium ascorbate, catalase). Compound 23 did not show any detectable oxidation potential (determined by NO monitor). Agarose gel electrophoresis demonstrated that compound 23 induced DNA fragmentation in human promyelocytic leukemia cells HL-60, but not in HSG cells. These data suggested that the response to compound 23 might be different from cell to cell.
 ...
PMID:Cytotoxic activity of 5-benzoylimidazole and related compounds against human oral tumor cell lines. 1139 43


1 2 3 4 5 6 7 Next >>