UMLS:C0027651 - FACTA Search

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)

We developed a method for production of antigen-specific, H-2-restricted T cell hybrids. The tumor cell partner in the fusions was itself a T cell hybrid, FS6-14.13.AG2 (or its derivatives), which could be induced to produce the growth factor, interleukin-2 (IL-2), in response to a challenge with concanavalin A, but had no known antigen specificity. The normal T cell partner in the fusions was a population of lymph node T cell blasts that had been highly enriched in antigen-specific, H-2-restricted T cells by in vivo immunization, followed by in vitro challenge with antigen and clonal expansion in IL-2-containing medium. These fusions produced hybrids that grew constitutively in culture. A sizable proportion of the hybrids demonstrated the ability to produce IL-2 in response to a challenge with specific antigen presented by irradiated spleen cells of the appropriate H-2 type. Four cloned antigen/H-2-specific hybrid lines were produced. AO-40.10 responded to chicken ovalbumin (OVA) when presented by I-A(k)-bearing cells. DC1.18.3 responded to the apo form of beef cytochrome c when presented with I-A(d). AODK-10.4 responded to keyhole limpet hemocyanin (KLH) presented with I-A (d). AODK-1.16 also responded to KLH presented by a product of the I region of H-2(d), but the data were consistent with either a product of the I-J-I-E(d) region or a combinatorial molecule with elements from both I-A(d) and I-E(d)/I-C(d). Coincidentally, AO-40.10 was shown to have an unexpected alloreactivity with a product of H-2(b) mapping to the K-I-A region. These hybrids should prove invaluable as sources of monoclonal material for the study of the receptor(s) on T cells with H-2-restricted antigen specificities. We also generated T cell hybrids with two antigen/H-2 specificities by fusing an azaguanine-resistant clone of AO-40.10 to normal T cells with a different antigen/H-2 specificity. Many of the hybrids retained reactivity to OVA plus H-2(a) and to the second antigen/H-2 combination. None reacted to either OVA plus the second H-2 type or to the second antigen plus H-2(a). One of these hybrids was successfully cloned to produce the line AOFK- 11.11.1. It retained the ability to recognize OVA plus I-A(k) inherited from one parent, and KLH plus IA(f) inherited from the other. It did not recognize OVA plus IA(f) or KLH plus I-A(k). These results have some bearing on models describing the nature of T cell receptors for antigen recognized in association with H-2 products. They do not support models in which antigen and H-2 are recognized separately by two independent T cell receptors.
...
PMID:Antigen-inducible, H-2-restricted, interleukin-2-producing T cell hybridomas. Lack of independent antigen and H-2 recognition. 616 12

Blood samples from closely monitored patients at the Veterans Administration Hospital in Houston, Texas, were collected, coded, and sent to Microbiological Associates over an 8-month period. Lymphocytes were isolated and cryopreserved at -190 degrees. Lymphocyte samples were simultaneously thawed, phytohemagglutinin activated, and analyzed for benz(a)anthracene-induced aryl hydrocarbon hydroxylase (AHH) levels, [3H]thymidine incorporation, and reduced nicotinamide adenine dinucleotide-dependent cytochrome b5 (cytochrome c) reductase activity. Determinations were made at both 96 and 120 hr in culture, and peak activities were compared among a total of 51 individuals who expressed such lesions as squamous cell carcinomas (22%), adenocarcinomas (14%), oat cell carcinomas (6%), chronic obstructive pulmonary disease (22%), and other nonmalignant diseases. Of the 14 highest AHH/cytochrome c activities observed, all were found in patients with primary lung cancer. Mean AHH/cytochrome c activities were 0.89 for lung cancer patients (a total of 21) and 0.47 for noncancer patients (a total of 30) (p less than 0.001). No relationship was observed between AHH/cytochrome c activity and age of patient, numbers of cigarettes smoked, family history of cancer, location or histological type of tumor, or level of phytohemagglutinin blastogenesis ([3H]thymidine cpm/cytochrome c). Whether the higher AHH levels are the cause or the result of the primary lung cancer remains to be determined.
...
PMID:Positive correlation between high aryl hydrocarbon hydroxylase activity and primary lung cancer as analyzed in cryopreserved lymphocytes. 629 46

The mechanism(s) of natural killer (NK) cell-mediated cytotoxicity (CMC) remains largely unknown. In this study, we investigated the possibility of human NK cells to exhibit an oxidative burst (OB) after stimulation by K562, an NK-sensitive target cell (TC). The addition of catalase (CAT) or superoxide dismutase (SOD) to the NK-mediated cytotoxic assay had no effect on NK-CMC. In contrast, CAT and SOD effectively modulated the cytotoxicity mediated by phorbol-12-myristate-13-acetate (PMA)-activated polymorphonuclear leukocytes (PMNL) against three different tumor TC, including K562. CAT abrogated, while SOD enhanced PMA-activated PMNL-mediated cytotoxicity. The synergistic effect of SOD and PMA was suppressed in a dose-dependent fashion by CAT. Furthermore, by chemiluminescence (CL) and SOD-inhibitable reduction of cytochrome c, we failed to detect an OB associated with K562-stimulated NK cells. PMNL, however, rapidly responded to PMA (10 ng/ml), generating almost 10(6) cpm within 20 min and 26.7 nM O-2/10(6) cells/30 min, as detected by CL and reduction of cytochrome c, respectively. Finally, K562 alone, at cell concentrations corresponding to effector cell:target cell (EC:TC) ratios of 1:1 and 1:10, reduced cytochrome c, but this reduction was not inhibited by SOD, thus suggesting a diaphorase activity. Overall, we show that: a) tumor cell destruction by human NK cells and by PMA-activated PMNL is mediated by different mechanisms; and b) NK-CMC against a sensitive TC does not involve an OB.
...
PMID:Compared mechanisms of tumor cytolysis by human natural killer cells and activated polymorphonuclear leukocytes. 632 20

Metabolic or synthetic N-hydroxylation of N-arylamides yields N-arylacylhydroxamic acids considerably more carcinogenic for the rat mammary gland than the parent amides both by systemic and topical administration. The size of the aryl moiety, the position of the nitrogen relative to the aryl moiety and the type of acyl group are determinants of the carcinogenic potency of N-arylacylhydroxamic acids. Induction of mammary tumors required ovarian hormones. Receptors for estrogen, androgen and progesterone were shown in the N-hydroxy-N-2-fluorenylacetamide (N-OH-2-FAA)-induced mammary carcinoma. This tumor involved epithelial and stromal components of the mammary gland that were separated in culture and produced tumors of their respective origin in the isologous host. Both mammary epithelial cells and fibroblasts are capable of metabolism of carcinogens. The enzymes potentially involved in metabolic activation of N-arylamides and N-arylacylhydroxamic acids in the mammary gland include: a cytochrome P-450(P(1)-450) system, UDP-glucuronyltransferase, N,O-acyltransferases and peroxidases. Mammary microsomes in which cytochrome P(1)-450 was induced generated small amounts of N-OH-2-FAA from 2-FAA. N-OH-2-FAA and its carcinogenic isomer, N-OH-3-FAA, were oxidized by cytochrome c/H(2)O(2) to the nitroxyl free radicals which dismutated to the respective acetate esters and nitrosofluorenes. The addition of unsaturated lipid to either the free radicals or to the nitrosofluorenes gave electron spin resonance signals characteristic of immobilized radicals. It is proposed that interactions of carcinogens with lipids and with DNA play a role in mammary tumorigenesis.
...
PMID:Pathobiologic and metabolic aspects of mammary gland tumorigenesis by N-substituted aryl compounds. 633 24

Mouse peritoneal macrophages (MPM) from C57BL/6J, BALB/c, A strains, and (BALB/ cfemale X C57BL/ 6Jmale )F1 offspring were treated with the oxidative burst (OB)-stimulant 12-O-tetradecanoylphorbol 13-acetate, and their in vitro tumoricidal, tumorostatic , and OB activities were examined. Paraffin oil-elicited, but not thioglycollate (TG)-elicited, MPM exhibited cytotoxicity only toward Yac-1 cells and cytostatic activity toward Yac-1, EL 4, RBL-5, and RLmale 1 lymphoma cells. This activity was in correlation with the reduced capacity of TG-elicited cells to generate OB products. The toxic effect of such activated MPM was partially inhibited by catalase, superoxide dismutase, cytochrome c, and vitamin E (alpha-tocopherol) and was augmented by horseradish peroxidase and the catalase inhibitor aminotriazole (3-amino-1H-1,2,4-triazole), thus indicating the involvement of oxygen-derived toxic reagents, mainly hydrogen peroxide, in the MPM-mediated damage inflicted on the tumor cells. EL 4 cells incubated with nonstimulated MPM exhibited enhanced growth both in vitro and in vivo, whereas OB-stimulated MPM inhibited the growth of such cells in the same experimental systems.
...
PMID:Oxidative burst-dependent tumoricidal and tumorostatic activities of paraffin oil-elicited mouse macrophages. 658 55

We have established a system in which a human cell line generated reactive oxygen species (ROS), using a dimethyl sulfoxide-differentiated promyelocytic leukemia cell line HL60 (DMSO-HL60), which has characteristics similar to those of human neutrophils. DMSO-HL60 generated O2- upon stimulation with a tumor promoter, phorbol myristate acetate (PMA). O2- generation, determined as O2- release from the PMA-stimulated cells by the reduction of cytochrome c, was dependent on the dose of PMA and reached almost maximal with 2.0 nM PMA. PMA dose-dependently increased 8-hydroxydeoxyguanosine (8OHdG) in DMSO-HL60, typical of mutagenic oxidative DNA damage. The 8OHdG level, determined by electrochemical detection with high performance liquid chromatography, also became almost maximal with 2.0 nM PMA. The amount of O2- generation and that of the 8OHdG induction by PMA in human neutrophils were similar to those in DMSO-HL60. Superoxide dismutase inhibited the 8OHdG induction by about 60%, whereas catalase, deferoxamine, or thiols inhibited it almost completely. Dilution of PMA-stimulated DMSO-HL60 decreased the concentration of ROS releasing to the media from the cells. However, it did not decrease the ROS generation per cell or the 8OHdG induction. The addition of H2O2 to unstimulated DMSO-HL60 did not increase the 8OHdG level. These findings indicate that DMSO-HL60 could be used as a substitute for human neutrophils, that the concentration of ROS is not the only determinant for the 8OHdG induction, but that it requires both acquisition of susceptibility to ROS by reduction of iron by O2- and formation of H2O2, and that ROS increase 8OHdG by attacking the ROS-generating cell.
...
PMID:Establishment of a human system that generates O2- and induces 8-hydroxydeoxyguanosine, typical of oxidative DNA damage, by a tumor promotor. 795 11

Mitomycin C (MC), a clinically used natural antitumor agent, was shown to form three monoconjugates (11a-13a) and two bisconjugates (14a, 15a) with GSH upon reductive activation by rat liver microsomes, purified NADPH-cytochrome c reductase, or NADH-cytochrome c reductase or chemical reduction using H2/PtO2. Rat liver cytosol/NADH activated MC only at acidic pH (5.8), resulting in the formation of a single GSH-MC monoconjugate, 13a. The reductase responsible for cytosolic activation of MC to form this conjugate was DT-diaphorase. GSH itself did not reduce MC, and unreduced MC did not form conjugates with GSH. A moderate catalytic effect by glutathione S-transferase was demonstrated on the cytosol-activated reaction. Mercaptoethanol and N-acetylcysteine gave analogous sets of five MC-thiol conjugates under cytochrome c reductase or H2/PtO2 activation conditions. The structures of all 15 MC-thiol conjugates (five each with GSH, mercaptoethanol, and N-acetylcysteine, respectively) were determined, using 1H-NMR, UV, and mass spectroscopies, combined with analytical chemical and radiolabeling methods. The mechanism of formation of the conjugates features SN2 displacement of the carbamate of the reduced MC by GS-. The MC-GSH conjugates were noncytotoxic to the tumor cells tested. The conjugation of GSH with activated MC is likely to represent detoxication in mammalian cells. As another effect, GSH accelerates the rate of reduction of MC by "slow" reducing agents such as cytochrome c reductases and H2/PtO2. A mechanism is proposed to explain this effect, which involves further reduction of the initially formed MC semiquinone free radical by GSH.
...
PMID:Conjugation of glutathione and other thiols with bioreductively activated mitomycin C. Effect of thiols on the reductive activation rate. 807 71

The induction of apoptosis of tumor cells by the colonic fermentation product butyrate is thought to be an important mechanism in protection against colorectal cancer. Because a major action of butyrate is to inhibit histone deacetylase (leading to chromatin relaxation and altered gene expression), butyrate may induce apoptosis by derepression of specific cell death genes. Here we show that butyrate and trichostatin A (a more selective inhibitor of histone deacetylase) induce the same program of apoptosis in Jurkat lymphoid and LIM 1215 colorectal cancer cell lines that is strictly dependent on new protein synthesis (within 10 h) and that leads to the conversion of the proenzyme form of caspase-3 to the catalytically active effector protease (within 16 h) and apoptotic death (within 24 h). Cells primed with a low concentration of butyrate that itself did not induce activation of caspase-3 or apoptosis were, nevertheless, rendered highly susceptible to induction of apoptosis by staurosporine (an agent that has recently been shown to act by causing mitochondrial release of cytochrome c). Synergy between butyrate and staurosporine was due to the presence of a factor in the cytosol of butyrate-primed cells which enhanced over 7-fold the activation of caspase-3 induced by the addition of cytochrome c and dATP to isolated cytosol. We propose that changes at the level of chromatin structure, induced by a physiological substance butyrate, lead to the expression of a protein that facilitates the pathway by which mitochondria activate caspase-3 and trigger apoptotic death of lymphoid and colorectal cancer cells.
...
PMID:Induction of caspase-3 protease activity and apoptosis by butyrate and trichostatin A (inhibitors of histone deacetylase): dependence on protein synthesis and synergy with a mitochondrial/cytochrome c-dependent pathway. 928 76

There is currently much interest in the possibility that dietary antioxidants may confer protection from certain diseases, such as atherosclerosis and cancer. The importance of alpha-tocopherol (vitamin E) as a biological antioxidant is widely recognized. However, pro-oxidant properties of alpha-tocopherol have been observed in chemical systems, and it has been reported that the vitamin can induce tumor formation and act as a complete tumor promotor in laboratory animals. In the present communication, we find that alpha-tocopherol can act as a potent DNA-damaging agent in the presence of copper(II) ions, using a simplified, in vitro model. alpha-Tocopherol was found to promote copper-dependent reactive oxygen species formation from molecular oxygen, resulting in DNA base oxidation and backbone cleavage. Neither alpha-tocopherol nor Cu(II) alone induced DNA damage. Bathocuproine, a Cu(I)-specific chelator, and catalase inhibited the DNA damage, whereas free hydroxyl radical scavengers did not. The order of DNA cleavage sites was thymine, cytosine > guanine residues. Examinations using an oxygen electrode and cytochrome c indicate that molecular oxygen was consumed in the reaction of alpha-tocopherol and Cu(II) and that superoxide was formed. Stoichiometry studies showed that two Cu(II) ions could be reduced by each alpha-tocopherol molecule. Electron spin resonance spin-trapping investigations were then used to demonstrate that hydrogen peroxide interacts with Cu(I) to generate the reactive species responsible for DNA damage, which is either the hydroxyl radical or a species of similar reactivity. These findings may be of relevance to the tumorigenic properties of the vitamin reported in the literature. However, further studies are required to establish the significance of these reactions under in vivo conditions.
...
PMID:Alpha-tocopherol induces oxidative damage to DNA in the presence of copper(II) ions. 970 46

In multicellular organisms, the control of cell proliferation occurs, in part, by modulating the progress in differentiation. In normal and neoplastic cells, for example, progress towards terminal differentiation concludes cell proliferation, whereas arrest of progress in differentiation causes uncontrolled cell proliferation. Evidence is presented according to which the progress in differentiation depends on an increase in the ratio between mitochondrial differentiation promoting activity and nuclear differentiation preventing activity. This ratio is low in embryonic cells and in stem cells, due to low mitochondrial content, but increases by a rate of mitochondrial multiplication that is larger than a doubling of mitochondrial content per cell cycle. The rate of mitochondrial multiplication, thus, decides on the progress in differentiation and controls the number of amplification divisions between cell determination and terminal differentiation. This rate is modifiable by extracellular signals and cellular defects. Mutations, for example in nuclear genes coding for mitochondrial proteins, are likely to decrease the rate so much that differentiation is arrested with ensuing neoplastic growth. Agents used in differentiation therapy and ionizing radiation overcome this arrest: the cell cycle is sensitive to these agents, but not the mitochondria which multiply during the transitory cell cycle inhibition, thus increasing the differentiation promoting activity. Differentiation arrest can be circumvented also by direct inhibition of nuclear differentiation preventing activity at the level of transcription or translation, whereas corresponding inhibition of mitochondrial differentiation promoting activity prevents differentiation. Accumulation of non-specific genetic damage causes persisting cell cycle prolongation and enhancement of differentiation which, apparently, are involved in senescence. The recent finding of increase in mitochondrial mass prior to release of cytochrome c, induction of differentiation, and apoptosis points to similarities in the initial molecular pathways of differentiation and apoptosis.
...
PMID:Control of cell proliferation by progress in differentiation: clues to mechanisms of aging, cancer causation and therapy. 974 59

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