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 peptide N-formyl-Met-Leu-Phe stimulates chemotaxis and metastasis in rat Walker carcinosarcoma cells by a receptor-mediated pathway. Since oxygen radical generation follows chemotactic stimulation in leukocytes, we looked for similar responses in the Walker tumor. Upon incubation with 10(-6) M N-formyl-Met-Leu-Phe, Walker cells elicited chemiluminescence in the presence of 5 X 10(-5) M luminol. The response peaked within 2 min and was maintained for greater than 20 min; it was dose dependent with a 50% maximal effective dose (ED50) value of 4.5 X 10(-8) comparable to the 50% maximal effective dose value for chemotaxis. The responses were significantly reduced but not abolished in the absence of calcium in the external medium and were elicited by the ionophore A23187. The lipoxygenase inhibitor nordihydroguaiaretic acid had almost no effect in decreasing the response, while flurbiprofen, a cyclooxygenase inhibitor was very effective at 10(-6) M. Evidence for the generation of oxygen radicals included: (a) marked inhibition of light emission in the absence of oxygen; (b) inhibition in the presence of superoxide dismutase, catalase, and mannitol; and (c) dose-dependent reduction of acetylated cytochrome c. We postulate that activation of circulating tumor cells may facilitate metastasis by the release of toxic oxygen species.
 ...
PMID:Chemiluminescence and oxygen radical generation by Walker carcinosarcoma cells following chemotactic stimulation. 304 Feb 30

In an attempt to characterize metabolism enzymes of the estrogen-induced kidney tumor in male Syrian hamsters, the activities of enzymes involved in drug and glutathione metabolism were determined in tumor tissue. Kidney tumors were induced in male Syrian hamsters by treatment with estradiol for 8 months. Cytochrome P-450 and cytochrome b5 concentrations in tumors were below detectable levels. However, when cytochrome P-450-mediated oxidation was analyzed by product formation assays, the oxidation of E-diethylstilbestrol to diethylstilbestrol-4',4"-quinone by tumor microsomes was 10-20% of the rate found in control microsomes. In kidney tissue surrounding estrogen-induced tumors, cytochrome P-450 and b5 contents were 50-60% less than those in untreated kidney. Activities of reducing enzymes of drug metabolism (cytochrome P-450, cytochrome b5 and NADH:cytochrome c reductases), glutathione metabolism enzymes (glutathione peroxidase, glutathione transferase, glutathione reductase, and gamma-glutamyl transpeptidase), and free radical scavenging enzymes (superoxide dismutase, catalase, and quinone reductase) in tumor were significantly lower than in untreated kidney tissue. The activities of these enzymes in renal tumor surrounding tissue were between those observed in tumor and control kidney. Glucose-6-phosphate dehydrogenase activity was increased by 50% in surrounding tissue and 430% in tumor compared to values in untreated controls. The decreased enzyme activity levels in hormone-exposed tissue surrounding tumors likely represented an adaptation of this tissue to the neoplastic environment induced by chronic estrogen treatment.
 ...
PMID:Characterization of drug metabolism enzymes in estrogen-induced kidney tumors in male Syrian hamsters. 304 47

The present study was designed to characterize the production of chemoattractants by human melanoma lines with high (M4Be, M3Da, NTerDa) or low tumorigenic (Doc8, M1Do) potential when heterotransplanted in nude mice. Supernatants from the Doc8 and M1Do cell lines were strongly chemotactic in vitro for mononuclear phagocytes. Chemotactic activity was destroyed by proteolytic enzymes, and upon gel filtration on Sephadex G75, it eluted in the cytochrome c region corresponding to an apparent m.w. of 12,000. Upon chromatofocusing, the Sephadex-separated tumor-derived chemotactic factor (TDCF) showed an isoelectric point of 5.5 to 6. Cell lines with high tumorigenic potential contained low or no detectable chemotactic activity. When culture supernatants of cell lines with modest (M3Da) or no (M4Be) chemotactic activity were exposed to immobilized monoclonal antibodies directed against the retroviral transmembrane protein P15E, appreciable chemotactic activity was detectable (M4Be) or preexisting levels increased (M3Da). The material eluted from Sepharose-bound anti-P15E antibodies inhibited the migration of monocytes in response to chemoattractants. These findings demonstrate the coexistence in some human melanoma cell line supernatants of factors (TDCF and P15E-related inhibitor) with opposite influence on monocyte chemotaxis. That tumor cell products play a pivotal role in regulating the extravasation of monocytes into neoplastic tissues is suggested by the close correlation observed between macrophage levels in melanomas grown in nude mice and levels of chemotactic activity detectable in culture supernatants.
 ...
PMID:Chemotactic factor and P15E-related chemotaxis inhibitor in human melanoma cell lines with different macrophage content and tumorigenicity in nude mice. 310 64

We have investigated the nitroreduction of the 2-nitroimidazole benznidazole (BENZO) to its corresponding amine by murine normal tissues and tumours. In vivo concentrations of BENZO and its amine metabolite were measured by HPLC 3 hr after BENZO, 2.5 mmoles kg-1 i.p. This gave plasma and tissue BENZO concentrations of 96-160 micrograms ml-1 or g-1. Mouse plasma, KHT and RIF-1 tumour BENZO amine concentrations were very low (0.3-1.4 micrograms g-1); kidney and EMT6 tumours had intermediate levels; and liver contained very high amine levels (approximately 50 micrograms g-1). Three per cent of the BENZO dose was recovered as amine in the 24 hr urine, compared to 5% for the parent compound. Nitroreduction to the amine was demonstrated with liver and tumour preparations under N2 in vitro. The reaction was highly dependent on NADPH, and inhibited extensively in air. With liver microsomes and whole homogenates 2 and 3 moles respectively of BENZO were consumed per mole of amine formed. Inhibitor studies showed that NADPH: cytochrome P-450 (cytochrome c) reductase and cytochrome P-450 were both involved in BENZO reduction, predominantly at early and late reduction steps respectively. Aldehyde oxidase contributed to the cytosolic nitroreduction. Purified buttermilk xanthine oxidase also reduced BENZO to its amine under anaerobic conditions in vitro, but very inefficiently. The apparent Km and Vmax for BENZO amine production by whole liver homogenates were 0.148 mM and 1.45 nmole min-1 mg-1 protein respectively. Tumour homogenates were less active than liver; e.g. Vmax for the KHT tumour was 6-10-fold lower.
 ...
PMID:Nitroimidazole bioreductive metabolism. Quantitation and characterisation of mouse tissue benznidazole nitroreductases in vivo and in vitro. 310 39

When a streptococcal preparation, OK-432, was administered intraperitoneally to patients with malignant ascites, the number of neutrophils with cytotoxic activity against tumor cells was increased in the peritoneal cavity immediately after the OK-432 injection. In order to investigate the underlying mechanisms of such neutrophil accumulation, a possible neutrophil chemotactic activity in ascitic fluid was assayed by a modified Boyden method. The chemotactic activity for neutrophils was found significantly higher 6 hr after the OK-432 injection. OK-432 along had no direct chemotactic activity for neutrophils. The chemotactic activity was generated in vitro when ascitic fluid from patients without OK-432 treatment was incubated with OK-432 for 30 min at 37 degrees C. However, preheating of the fluid at 56 degrees C for 30 min or the addition of EDTA to the fluid resulted in the failure of generation of the chemotactic activity after the incubation with OK-432. The addition of EGTA did not show a significant effect. The chemotactic activity in ascitic fluid was found near cytochrome c marker (MW 12,400 D), when fractionated by Sephadex G-200 gel chromatography. The chemotactic activity was heat stable, nondialyzable, and neutralized completely with anti-human complement C5 antibodies. These results suggest that C5a generated via the alternative pathway activated by OK-432 may be responsible for the infiltration of killer neutrophils in the peritoneal cavity in patients with malignant ascites when they are treated by the intraperitoneal injection of OK-432.
 ...
PMID:Neutrophil-mediated tumor cell destruction in cancer ascites. II. A OK-432 attracts killer neutrophils through activation of complement C5. 310 38

The effects of PSK and Propionibacterium acnes (anaerobic Corynebacterium) on hepatic drug-metabolizing enzymes were studied using sarcoma-180 bearing and non-tumor bearing mice. PSK had no influence on aminopyrine N-demethylase and aniline hydroxylase activities, cytochrome P-450 concentration in hepatic microsomes, and the reductase activity of cytochrome c in normal mice. The content of cytochrome P-450 was not significantly reduced in S-180 bearing mice. On the other hand, P. acnes administration significantly decreased the amount of cytochromes P-450 and b5 and aminopyrine N-demethylase activity. When FT-207 (Tegafur) was administered orally to S-180 bearing mice combined with the immunoadjuvants, only P. acnes significantly reduced the 5-FU levels in the serum and some organs.
 ...
PMID:Effect of PSK, a protein-bound polysaccharide from Coriolus versicolor, on drug-metabolizing enzymes in sarcoma-180 bearing and normal mice. 313 76

Rheumatoid arthritis (RA) sera were evaluated for anti-idiotypic (anti-id) antibodies to HLA-DR antigens (anti-DR) using an ELISA method with murine monoclonal anti-DR antibody-coated microtiter plates incubated serially with either normal or RA sera and peroxidase-conjugated goat anti-human IgG (Fc specific). Specificity was examined using other monoclonal antibodies including anti-Leu 3a, OKM5, OKT8, anti-cytochrome c, and anti-breast tumor antigen. Significant binding of 11/33 (33%) RA to anti-DR was found compared with 0/44 normals (P less than 0.001). Two groups were identified: RA sera reacting with anti-DR and anti-Leu 3a and sera which did not bind to anti-DR but bound to irrelevant monoclonal antibodies. Anti-DR reactivity was differentiated from anti-Leu 3a by competitive inhibition studies. Binding of whole sera and IgG from RA patients to anti-DR was significantly inhibited by DR+ cell extract. The same extract was not inhibitory after selective removal of DR antigen by adsorption on an anti-DR-Sepharose column. These data suggest that anti-id antibodies are directed against the antigen-binding site of id. We conclude that some RA patients have anti-id antibodies potentially involved in immunoregulation of anti-DR antibodies.
 ...
PMID:Anti-idiotypic antibodies to anti-DR in patients with rheumatoid arthritis. 349 18

Liver microsomes of the rat contain a group of hydroxylating enzymes which are coupled to a greater or lesser degree to the electron flow system. In our studies, enzymes believed to be directly associated with the electron flow chain of NADPH, ferricyanide reduction, cytochrome c, cytochrome P-450 and substrate hydroxylation have been observed in livers obtained from normal, tumor-bearing and whole body irradiated rats as well as in Morris hepatoma 7777 and dimethyl-amino-biphenyl induced breast tumors.A significant difference appeared to exist in the activity of NADPH oxidase, NADP-ferricyanide reductase and benzopyrene hydroxylase when normal liver was compared with the liver obtained from a breast-tumor-bearing animal. Both cytochrome P-450 and cytochrome b(5) were decreased in the tumor-bearing animal.Tissue distribution of benzopyrene hydroxylase in normal, lactating and tumor-bearing Wistar rats has been studied.With the exception of NADPH oxidase, the activities of NADP-cytochrome c reductase, NADPH-ferricyanide reductase, benzopyrene hydroxylase and P-450 were markedly different in liver from Morris hepatoma 7777-bearing Buffalo rat when this was compared with homologous tissue obtained from normal Buffalo rat.Whole-body irradiated animals showed increased P-450 and NADPH oxidase activity in liver as a function of irradiation and there further appeared to be a correlation with decreased ferricyanide reductase activity.
 ...
PMID:Mixed-function oxidation in tumors. 439 26

When human neutrophils (PMNs) are activated by appropriate stimuli, they aggregate, generate superoxide anion (O2-) and secrete lysosomal enzymes. Pre-incubation of PMNs in vitro with the cyclo-oxygenase (COx) inhibitor piroxicam (50 microM) before stimulation with the chemotactic peptide f-met-leu-phe (FMLP, 10(-7)M) inhibited all of these responses. The COx inhibitor ibuprofen inhibited FMLP-induced aggregation and lysozyme secretion, leaving O2- generation unaffected. Binding of 3H-FMLP was inhibited by piroxicam. When the plant lectin concanavalin A (Con-A, 30 micrograms/ml) or the tumor promoter phorbol myristate acetate (PMA, 50 micrograms/ml) was used as a stimulus, ibuprofen had no effect on PMN response, while piroxicam inhibited only O2- generation. To determine whether such inhibition might also occur in vivo, we tested neutrophil aggregation and O2- generation in response to FMLP in 26 normal subjects. These subjects were then administered therapeutic doses of piroxicam (20 mg/day), ibuprofen (2400 mg/day) or indomethacin (100 mg/day), and neutrophil functions were retested after 3 days. Piroxicam inhibited FMLP-induced aggregation by 31% (5.2 cm2/min versus 3.6 cm2/min, P less than 0.004) and O2- generation by 35% (15.8 nmol cytochrome c reduced versus 10.2 nmol, P less than 0.002). Ibuprofen inhibited FMLP-induced aggregation by 44% (5.2 versus 3.0, P less than 0.03) but had no effect on O2- production. Indomethacin inhibited FMLP-induced aggregation (6.4 versus 2.9, P less than 0.01) but had no effect on O2- generation.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:The inactivation of the polymorphonuclear leukocyte by non-steroidal anti-inflammatory drugs. 609 Mar 11

The microsomal stearoyl-CoA desaturase system was examined in both the Morris hepatoma 7288CTC, maintained in the host Buffalo strain rat, and the Morris hepatoma 7288C, maintained in tissue culture. In vitro examination shows the stearoyl-CoA desaturase system to be similar in the 2 tissues. Both show extremely low overall stearoyl-CoA desaturase activity, having 4% and 8% of normal liver values respectively. Examination of the electron transport system showed both tissues have decreased electron transport components cytochrome b5 and cytochrome b5 reductase. Particularly noticeable were the extremely low levels of cytochrome b5 (2% compared with normal liver). Microsomes from both tissues showed a decreased ability to reduce an artificial electron acceptor, cytochrome c. With the low levels of cytochrome b5 observed in these tissues, the low levels of overall desaturase activity may be caused by lack of terminal enzyme, lack of sufficient cytochrome b5, or both. Analysis of the stearoyl-CoA desaturase system in cultured hepatoma cells suggests that these cells are similar to the host-grown tumor in this respect and may be used as a model in further examinations of the stearoyl-CoA desaturase system.
 ...
PMID:Analysis of the stearoyl-CoA desaturase system in the Morris hepatoma 7288C and 7288CTC. 614 13


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