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 inhibitory effects of 151 natural products, representing most of the frequently occurring types, on the cytotoxicity to MM2 tumor cells of polymorphonuclear leucocytes (PMN) induced by TAK, a polysaccharide immunomodulator, were examined. Forty-two compounds inhibited the TAK-induced activation of PMN. Among them, some naturally occurring quinones and various alkaloids (nicotine, Cinchona alkaloids, isoquinoline alkaloids such as cepharanthine, and indole alkaloids such as ajmaline) exhibited potent inhibitory effects. Using the inhibition assay for monitoring, the extracts of Hydrangea Dulcis folium, Scopoliae rhizoma, Cinchona cortex, Magnoliae cortex, Stephania tuber, and Rauwolfia radix were analysed to characterize the active constituents.
 ...
PMID:Inhibitory effects of plant secondary metabolites on cytotoxic activity of polymorphonuclear leucocytes. 152 25

The antitumor activity of mouse polymorphonuclear leukocyte (PMN) treated with a beta-1,3-D-glucan from Alcaligenes faecalis var. myxogenes IFO 13140 (TAK-N) and its carboxymethylated derivative (CM-TAK) was investigated in vitro and in vivo. ICR mouse PMN showed strong cytotoxicity against sarcoma 180 cells and inhibition of the growth of the tumor cells in vitro in the presence of TAK-N but not in the presence of CM-TAK. Since the cytotoxicity induced by TAK-N was almost completely inhibited by catalase, it seems to be mediated by H2O2 production by PMN. On the other hand, TAK-N induced no cytotoxicity in macrophages and neither did CM-TAK in PMN or in macrophage. Intraperitoneal injection of TAK-N into ICR mice induced a large number of PMN and macrophages in the peritoneal cavity. The peritoneal exudate PMN which were harvested at 10 to 72 h after TAK-N injection showed cytotoxicity against sarcoma 180 cells, but the peritoneal exudate macrophages did not. Treatment of sarcoma 180 ascites tumor-bearing ICR mice with TAK-N at a dose of 100 mg/kg prolonged significantly the survival time over that of the control. These results indicate that TAK-N induces PMN cytotoxicity against sarcoma 180 cells not only in vitro but also in vivo. The antitumor effect of TAK-N on sarcoma 180 ascites tumor seems to be derived from PMN stimulated with TAK-N.
 ...
PMID:Antitumor activity of polymorphonuclear leukocytes activated by a beta-1,3-D-glucan. 177 6

A potent tumor-regressing activity was found in the serum of mice with S180 tumor undergoing rapid regression caused by antitumor polysaccharides. Beta (1-3) glucan including CM-TAK and lentinan and mannoglucan MGA induced such activity. It causes a rapid decrease in the number of tumor cells accompanied with a marked increase in neutrophiles in solid tumors. The entity of the activity was named as tumor-regressing factor (TRF) and was partially purified revealing a proteinaceous nature with an approximate molecular weight of 250,000. The factor was induced in a serum of tumor-bearing mice in various host-tumor combinations after the tumor growth had been established but only weakly in normal mice. The sensitivity of tumors to the factor was also dependent on the stage of tumor growth. The serum of normal mice or tumor-bearing mice without polysaccharide treatment exhibited similar activity as TRF after definite chromatographic step. The chromatographic behavior of the revealed activity was closely similar to that of the induced factor. It was postulated that a TRF-like activity exists in normal serum in a inactivated form being bound by antagonist(s) and the appropriate chromatography might remove the antagonist resulting in the active form of the factor. The concept was confirmed by reconstituting the chromatographic fractions, the revealed activity was again obscured after mixing with a certain fraction.
 ...
PMID:[Tumor-regressing factor induced by antitumor polysaccharide in the serum of tumor-bearing mice]. 208 76

It has been reported that beta-1,3-D-glucan isolated from Alcaligenes faecalis (TAK) promoted tumor cytolysis by mouse polymorphonuclear leukocytes (PMN). We investigated the effect of serum on mouse PMN tumor cytolysis induced by TAK and other PMN stimulators. Addition of fetal calf serum (FCS) to the cytolysis assay enhanced tumor cytolysis by PMN in a dose-dependent manner. Sera obtained from horses, mice, and rats were also effective enhancers of PMN tumor cytolysis. When FCS was added after the assay was under way, the enhancing effect decreased proportionally to the time elapsed. The enhancing activity was detected over a broad range of fractions with a peak at 170 kD by fractionation on a Superose 6 column. The responsible factor(s) in serum was stable after treatment at 60 degrees C, 30 min or after lowering the pH to 2. Mouse PMN stimulated with TAK increased production of hydrogen peroxide in the presence of FCS.
 ...
PMID:Enhancement of polymorphonuclear leukocyte-mediated tumor cytotoxicity by serum factor(s). 210 49

Polymorphonuclear leukocytes (PMN) of mice can destroy tumor cells effectively in vitro in the presence of antitumor polysaccharide, linear beta-1, 3-D-glucan from Alcaligenes faecalis var. myxogenes IFO 13140 (TAK), and some other immunomodulators. In the present study, we investigated the mechanism of the tumoricidal activity of PMN induced by these immunomodulators and especially TAK. The TAK-induced PMN cytotoxicity was concluded to involve hydrogen peroxide from the following results: (a) the cytotoxicity depended on glucose consumption; (b) it was almost completely inhibited by catalase but not affected by superoxide dismutase; (c) it was not reduced by cyanide or azide, which are inhibitors of myeloperoxidase; (d) it was not affected by scavengers of singlet oxygen or hydroxyl radical; (e) release of hydrogen peroxide from PMN was observed by the addition of TAK; (f) MM46 target cells were lysed directly by hydrogen peroxide in the absence of myeloperoxidase; (g) the supernatant of PMN in the presence of TAK, tested as a stable cytotoxic factor, did not have cytotoxic activity, and protease inhibitors had no effect on this cytotoxicity. These results suggest that hydrogen peroxide is a direct cytotoxic mediator in TAK-induced PMN cytotoxicity. Next, the mechanism of PMN cytotoxicities induced by other immunomodulators was also examined and was compared with that induced by TAK. The results suggest that hydrogen peroxide is also important for these cytotoxicities whereas, unlike the results with TAK, the H2O2:halide:myeloperoxidase system may partly participate in the cytotoxicities with some immunomodulators.
 ...
PMID:Hydrogen peroxide as a tumoricidal mediator of murine polymorphonuclear leukocytes induced by a linear beta-1,3-D-glucan and some other immunomodulators. 299 Jun 72

Tumor promoters were tested for the ability to induce cytocidal activity of polymorphonuclear leukocytes (PMNs), and the extracellular calcium-dependency of their PMN cytotoxicities were examined in comparison with that by some immunomodulators. Immunomodulators such as linear beta-1, 3-D-glucan (TAK) induced potent cytocidal activity of PMNs. The induction was dependent on extracellular Ca2+. Tumor promoters such as phorbol 12-myristate 13-acetate (PMA) and its derivatives, teleocidin which is structurally unrelated to PMA, and croton oil as an example of mixture also induced potent PMN cytotoxicities. In the latter cases, however, the induction was not dependent on extracellular Ca2+. The ability of these tumor promoters to induce PMN cytotoxicity correlated well with their skin-tumor promoting activities. These results indicate that inductions by PMA-like tumor promoters are distinguishable from those by TAK-like immunomodulators in not being Ca2+-dependent. The application of Ca2+-independent PMN cytotoxicity to detect PMA-like tumor promoters is discussed.
 ...
PMID:Calcium-independent induction of cytocidal activity of polymorphonuclear leukocytes by phorbol myristate acetate-like tumor promoters. 308 66

Local induction of a cytotoxic factor (CF), which was reported by us to be a tumor necrosis factor (TNF)-like molecule, in murine tumor tissues by i.v. administration of antitumor polysaccharides was studied. The CF was measured by cytolysis assay against L929 fibroblasts in vitro. The antitumor polysaccharides mannoglucan polyalcohol (MGA), lentinan, carboxymethyl-(1----3)-beta-D-linear glucan DP540 (CM-TAK) and yeast mannan induced the CF in MH134 hepatoma tissues inoculated intradermally, with MGA inducing the highest level of the CF. MGA induced the CF in MM46 mammary carcinoma, Ehrlich carcinoma, and MH134 hepatoma, the growth of which were all inhibited by MGA, but not in Lewis lung carcinoma and EL-4 lymphoma, which are therapeutically resistant to MGA. MGA induced the CF in solid MH134 hepatoma tissues inoculated subcutaneously or intramuscularly as well as intradermally, but not in ascitic fluids with intraperitoneal MH134 hepatoma on which MGA is ineffective. These findings suggest that CF induction is correlated with the antitumor activity of polysaccharides. CF induction in tumor tissues was detectable 6 h after i.d. inoculation of MH134 hepatoma. Even in nontumorous inflammatory skin tissues produced by injection of TAK, the CF was induced by MGA. Thus, the early inflammatory reaction with accumulation of host cells and MGA treatment act cooperatively in local induction of the CF.
 ...
PMID:Local induction of a tumor necrosis factor (TNF)-like cytotoxic factor in murine tissues with tumorous and nontumorous inflammation after systemic administration of antitumor polysaccharides. 318 25

Marked tumor-regressing activity was induced in the serum of S180 tumor-bearing mice by injection of an antitumor polysaccharide, CM-TAK [carboxymethylated beta(1-3)glucan]. Maximal activity was induced 7-14 days after the tumor transplantation and 10-12 h after CM-TAK treatment. A quantitative assay for the activity was established on the basis of the initial decrease in the number of the tumor cells within 24 h. The factor with tumor-regressing activity was purified 10,000-fold by the series of hydroxylapatite chromatography, ammonium sulfate precipitation, anion-exchange chromatography, gel filtration, and boronate-mediated affinity chromatography. The molecular weight was estimated to be 250,000 by gel filtration. The activity was proteinase K sensitive, but relatively resistant to trypsin. Neuraminidase did not affect the activity. It is believed that the tumor-regressing factor is different from the tumor necrosis factor.
 ...
PMID:Antitumor polysaccharide-induced tumor-regressing factor in the serum of tumor-bearing mice: purification and characterization. 372 39

The antitumor polysaccharide CM-TAK [carboxymethylated beta(1-3)glucan] caused immediate and rapid loss of viable tumor cells from S180 solid tumors in ICR mice if it was given after a week of tumor growth. We found marked tumor-regressing activity in the serum of mice with S180 tumors undergoing CM-TAK-induced regression. When injected intravenously into S180-bearing mice, 0.1 ml of serum/mouse induced complete regression of day-14 tumors. However, in vitro cytotoxic activity against L929 and S180 cells was not detected. After the injection of CM-TAK or serum, along with the rapid decrease in tumor cells there was a marked increase in polymorphonuclear leukocytes. The serum was also active against fibrosarcoma Meth A in BALB/c mice, inducing partial regression or significant decrease in growth of the tumor. The properties of the factor in the serum seem to be different from those reported for tumor-necrotizing factor and other endogenous cytotoxic substances.
 ...
PMID:Rapid tumor regression caused by antitumor polysaccharide and induction of tumor-regressing factor in the serum of tumor-bearing mice. 373 42

A rapid decrease in the number of tumor cells from S180 tumors was caused by several antitumor polysaccharides including the beta (1-3)glucans lentinan and TAK-N and a mannoglucan MGA, but not by those lacking antitumor activity. MGA was demonstrated to induce potent tumor-regressing activity in the serum of tumor-bearing mice similar to that reported previously to be induced after an injection of CM-TAK, a carboxymethylated beta (1-3)glucan. It is probable that the induction of rapid regression of established tumors is a phenomenon common to antitumor polysaccharides and some microbiological products and that the tumor-regressing factor in the serum underlies a common mechanism.
 ...
PMID:Rapid tumor regression and induction of tumor-regressing activity in serum by various immune-modulating agents. 379 24


1 2 3 4 5 6 7 8 Next >>