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)

Complexes of 5-iodouracil (5IU) with Mn(II), Co(II), Cu(II), Zn(II), and Cd(II) ions have been prepared, characterized, and subjected to a screening system for evaluation of antitumor activity against Sarcoma-180 (S-180) and L 929 tumor cells. The complexes were characterized by their elemental analysis, infrared spectra, electronic spectra, magnetic measurements, and powder x-ray diffraction. The antitumor activity results indicate that some complexes have good antitumor activity both in vivo and in vitro against S-180 and L 929 tumor cells.
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PMID:Synthesis, characterization, and antitumor activity of 5-iodouracil complexes. 166 11

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.
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PMID:Intracellular DNA strand scission and growth inhibition of Ehrlich ascites tumor cells by bleomycins. 169 48

Microvascular proliferation, a hallmark of malignant brain tumors, represents an attractive target of anticancer research, especially because of the quiescent nonproliferative endothelium of the normal brain. Cerebral neoplasms sequester copper, a trace metal that modulates angiogenesis. Using a rabbit brain tumor model, normocupremic animals developed large vascularized VX2 carcinomas. By contrast, small, circumscribed, relatively avascular tumors were found in the brains of rabbits copper-depleted by diet and penicillamine treatment (CDPT). The CDPT rabbits showed a significant decrease in serum copper, copper staining of tumor cell nuclei, microvascular density, the tumor volume, endothelial cell turnover, and an increase in the vascular permeability (breakdown of the blood-brain barrier), as well as peritumoral brain edema. In non-tumor-bearing animals, CDPT did not alter the vascular permeability or the brain water content. CDPT also inhibited the intracerebral growth of the 9L gliosarcoma in F-344 rats, with a similar increase of the peritumoral vascular permeability and the brain water content. CDPT failed to inhibit tumor growth and the vascularization of the VX2 carcinoma in the thigh muscle or the metastases to the lung, findings that may reflect regional differences in the responsiveness of the endothelium, the distribution of copper, or the activity of cuproenzymes. Metabolic and pharmacologic withdrawal of copper suppresses intracerebral tumor angiogenesis; angiosuppression is a novel biologic response modifier for the in situ control of tumor growth in the brain.
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PMID:Inhibition of angiogenesis and tumor growth in the brain. Suppression of endothelial cell turnover by penicillamine and the depletion of copper, an angiogenic cofactor. 170 Jun 17

The report summarizes the work of our laboratory aimed at improving the understanding of the angiogenic response of adult tissues, an event that transforms a micro-embolus of neoplastic cells into a growing metastasis. Attention has been focused on tumor-induced angiogenesis. The following aspects of the subject are discussed: (a) relationship between size of vascular network and tumor growth rate or tumor cell population; (b) angiogenic capacity of tumors and role that prostaglandin E1 may have as an angiogenesis factor; (c) relationship between acquisition of angiogenic capacity and neoplastic transformation of a cell population; (d) modification of tissue composition at the onset of angiogenesis; (e) behaviour of copper ions and copper carriers in the course of the angiogenic response; (f) the influence of gangliosides on endothelial cell motility, survival and growth in vitro; (g) modulation of the angiogenic response by gangliosides (GM1, GT1b) in vivo.
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PMID:Gangliosides, copper ions and angiogenic capacity of adult tissues. 170 87

Methods were developed to test the angiogenic response to human tumor implants and various biologic agents in the cornea of rabbits and non-human primates (Macaca arctoides). Human malignant melanoma tissue and crude platelet derived growth factor (PDGF) preparations had significant angiogenic effects. Purified, recombinant PDGF preparations were also effective initiators. Hemorheologic agents which also inhibit platelet aggregation [e.g. pentoxifylline (Px) (Trental) (also found to release PgI2 and tissue plasminogen activator (t-PA)] inhibited human tumor implant-induced angiogenesis. Sodium diethyldithiocarbamate (DDTC), a metal complexing agent with special affinity to copper and anti-thyroid as well as immune stimulating activity, was shown to be anti-angiogenic and to increase the effect of Px. The anti-fibrinolytic agents epsilon amino caproic acid (EACA) and tranexamic acid (t-AMCHA) were anti-angiogenic.
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PMID:Studies on tumor induced angiogenesis. 172 79

Ternary Cu(II) complexes with bidentate malonato- and heterocyclic amine ligands were tested with regard to cytotoxicity and potentiation of x-ray induced cell killing in V79 cells. Two lead complexes were also tested in a tumor assay using the MTG-B murine adenocarcinoma model growing in the flanks of female C3H/HeJ mice. One complex, [2,2'-bipyridyl malonatoCu(II)] (RL-5077), produced sensitizer enhancement ratios (SER's) of 1.8 (hypoxic conditions) and 1.0 (oxic conditions) in vitro when irradiation followed 1 hr exposure to the drug at 100 microM. When RL-5077 was administered at doses of 1/2 (11.65 mg/kg) or 1/4 (5.25 mg/kg) the maximum tolerated dose (MTD), 15 min prior to a locally delivered dose of 20 Gy, enhancement ratios (ER's) of 1.6 and 2, respectively, resulted. The second lead complex, [1,10 phenanthroline (malonato)Cu(II)hydrate] (RL-5027), produced SER's of 1.8 and 1.2 under hypoxic and oxic conditions, respectively, at a concentration of 25 microM. Injection of RL-5027 (5 mg/kg) resulted in toxicity without enhancement in combination with radiation. Analogues of these two complexes have been synthesized in an effort to optimize the potentiation of radiation effects while minimizing toxicity to drug alone and increasing water solubility of the drug. Further studies of the structure-activity relationship of Cu(II) ternary complexes using in vitro radiosensitization as the endpoint have identified four classes of ligands with varying biological activity and have supplied information about the effects of group substitution on solubility, toxicity, and radiation potentiation. This group of complexes represents a new class of radiopotentiators that deserves further investigation into its potential for clinical use.
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PMID:Combined modality treatment with ternary Cu(II) complexes and X rays. 173

Two new strategies for increasing tumor uptake have been investigated. First the effect of interleukin-2 (IL-2) on tumor uptake of 125I-Lym-1 antibody in nude mice was investigated. Secondly, the use of 67Cu-labeled Lym-1 was evaluated in patients. In nude mice implanted with Raji human lymphoma, a greater than 2-fold enhancement of tumor uptake of 125I-Lym-1 was observed after administration of PEG-interleukin-2 (PEG-IL-2). The macrocycle 1,4,8,11-tetraazacylcotetradecane-N,N',N",N"'-tetraacetic acid (TETA), synthesized specifically for copper chelation, has been conjugated to Lym-1 for 67Cu labeling of the monoclonal antibody (MoAb). There was no evidence for bone or normal marrow uptake and the residence time in the tumor was prolonged. Surprisingly, a dose of 4.4 mCi that was intended for imaging induced substantial tumor regression in a patient.
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PMID:Strategies for enhancement of radioimmunotherapy. 174 86

Benzoyl peroxide (BzPO) is both a tumor promoter and progressor in mouse skin; however, BzPO is neither an initiator nor a complete carcinogen in this tissue. Although not mutagenic, BzPO has been observed to produce strand breaks in DNA of exposed cells. These actions are presumed to be mediated by free-radical derivatives of BzPO. Previous studies suggested that the metabolism of BzPO in keratinocytes proceeds via the initial cleavage of the peroxide bond, yielding benzoyloxy radicals which, in turn, can either fragment to form phenyl radicals and carbon dioxide or abstract H atoms from biomolecules to yield benzoic acid. Benzoic acid is the major stable metabolite of BzPO produced by keratinocytes. In the present study we have investigated the role of BzPO and its metabolites in the generation of strand scissions in a cell-free system using phi X-174 plasmid DNA. In this system BzPO produced DNA damage that was dose-dependent over a concentration range of 0.1-1 mM and required the presence of copper but not other transition metals. By contrast, benoic acid did not produce DNA damage in this system, either in the presence or in the absence of copper. The inclusion of spin trapping agents, such as N-tert-butyl-alpha-phenylnitrone (PBN), 3,5-dibromo-4-nitrosobenzenesulfonate, and nitrosobenzene, in incubations was found to significantly reduce the extent of DNA damage generated via the copper-mediated activation of BzPO. Electron paramagnetic resonance spectroscopy studies suggested that the primary radical trapped by PBN following copper-mediated decomposition of BzPO was the benzoyloxy radical.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of the benzoyloxyl radical in DNA damage mediated by benzoyl peroxide. 178 51

Copper-PTSM has been shown in previous studies to act as a fluid microsphere and to be useful in quantitating blood flow in brain, myocardium, and kidneys. In this study we have evaluated this agent as a PET tumor blood flow agent. 64Cu- or 67Cu-labeled Cu-PTSM was administered (i.v.) to Golden Syrian hamsters with colorectal carcinoma cell implants (GW39). One minute prior to sacrifice (10-60 min after Cu-PTSM was administered) 125I-iodoantipyrine (125I-IAP), an agent known to measure tumor blood flow, was administered intravenously by a 3-stage, 1 min ramp infusion. Following sacrifice, samples of tumor and brain were removed (within 40s) and the tumor and brain levels of Cu-PTSM and iodoantipyrine determined. Since the brain uptake of both Cu-PTSM and IAP is perfusion rate limited, the brain was used as a reference organ to normalize tumor levels of the two tracers. The plot of Cu-PTSM versus 125I-IAP tumor/brain ratios showed a good linear correlation (r value of 0.97), suggesting that Cu-PTSM could be used to quantify tumor blood flow. Since the mechanism of Cu-PTSM trapping is likely to be due to glutathione levels in the tissue, and because tumor tissue glutathione levels might vary, the temporal uptake of Cu-PTSM was investigated by PET imaging both the tumor-bearing hamsters and approximately 300 g Copenhagen rats bearing R3227 prostate tumors. The tumors were clearly visualized and the retained copper radioactivity in the tumor was constant over the 30 min imaging period.
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PMID:Investigation of copper-PTSM as a PET tracer for tumor blood flow. 178 92

The high kinetic stability of the Cu2+ complex of the chelator 4-[(1,4,8,11-tetraazacyclotetradec-1-yl)-methyl]benzoic acid was demonstrated at physiological pH as well as under acidic conditions. The chelating agent was conjugated to AB35, a monoclonal antibody directed against CEA, without a significant loss of immunoreactivity. The conjugate could, under optimal labeling conditions, be labeled with 67Cu in acetate buffer with a full occupancy of ligands within 20 min. This radiolabeled conjugate showed no transfer of radiocopper to serum proteins in human serum over 7 days. The biodistribution in tumor-bearing mice was measured and compared to that of iodinated AB35. Tumor uptake was high with 15 +/- 3% ID (injected dose)/g after 24 h and 32 +/- 7% ID/g after 96 h for the 67Cu-labeled antibody and 13 +/- 4% ID/g after 24 h and 14 +/- 2% ID/g after 96 h for the 125I-labeled antibody. Whereas radioactivity in normal organs decreased with time after 24 h, increased residence time was shown up to 4 days with the 67Cu-labeled AB35.
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PMID:Antibody labeling with copper-67 using the bifunctional macrocycle 4-[(1,4,8,11-tetraazacyclotetradec-1-yl)methyl]benzoic acid. 180 38


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