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T Sugimura

Publications and source records attributed to T Sugimura.

At least 559 records · Page 31Linked to original sources
PubMed1987

Analysis of tumor-promoter-induced inflammation in rats: participation of histamine and prostaglandin E2.

Inflammatory reactions induced by TPA (12-O-tetradecanoylphorbol 13-acetate)-type tumor promoters, including TPA, teleocidin and aplysiatoxin, and chemical mediators responsible for such inflammatory reactions were analyzed. The tumor promoter dissolved in a 0.8% sodium carboxymethyl cellulose solution was injected into a subcutaneous air pouch preformed on the dorsum of rats. Within 30 min after the injection, vascular permeability as measured by the leakage of labeled albumin into the pouch fluid was increased, with a concomitant increase in histamine level. This increase in vascular permeability was inhibited by a histamine antagonist, pyrilamine, and a serotonin antagonist, methysergide. Vascular permeability at 4 h was not inhibited by pyrilamine or methysergide but was inhibited by a cyclooxygenase inhibitor, indomethacin, with a parallel decrease in the prostaglandin E2 level in the pouch fluid. These results suggest that the TPA-type tumor promoters induce inflammation by the mechanism of mast cell degranulation within a short period, this being followed by the stimulation of arachidonic acid metabolism. The mechanism of the in vivo effect of the TPA-type tumor promoters is discussed and compared with in vitro effects that we have previously reported.

Animals↗
PubMed1987

Activation of human c-raf-1 by replacing the N-terminal region with different sequences.

Two transformants of NIH 3T3 cells, obtained by the transfection of human colon cancer and normal colon DNAs, contained activated c-raf-1. In both the activated c-raf-1, the 5' half of the c-raf-1 sequence was replaced by sequences other than c-raf-1 as a result of recombinations which occurred at the intron between exons 7 and 8. It was suggested, however, that these recombinations, which conferred the transforming activity on the c-raf-1, occurred during the transfection. In one case analyzed, characteristic sequences were found near the breakpoint and these may be involved in the recombination. It was found, upon analysing the structure of the cDNA derived from one of the activated c-raf-1, that fused mRNA had been transcribed from the recombined gene comprising the non-raf gene and c-raf-1. The mRNA possibly encodes a fused protein. One cDNA clone was derived from alternatively spliced mRNA, although its physiological role is unclear. On comparing the structure of the two human activated c-raf-1 and the rat activated c-raf which we have reported previously, it was revealed that, in these three cases, the sequences joined to the truncated c-raf(-1)1 were different. It was suggested from data which we and others have previously reported that various sequences could be capable of activating c-raf(-1) by replacing its 5' half.

Amino Acid Sequence↗
PubMed1987

Conservation of E6 and E7 regions of human papillomavirus types 16 and 18 present in cervical cancers.

The E6 and E7 regions of human papillomavirus (HPV) type 16 were present in the DNA samples from cervical cancer cell lines, SKG-IIIa and SKG-IIIb, and those from cervical cancer tissues of three different patients. T601 cells, an NIH3T3 transformant obtained by transfection of DNA from a surgical specimen of a cervical cancer, also contained the E6 and E7 regions. The E6 region of HPV type 16 was expressed as mRNA in SKG-IIIa, SKG-IIIb and T601 cells. The E6 and E7 regions of HPV type 18 were present in the DNA samples from cervical cancer cell lines, SKG-I and SKG-II, and those from cervical cancer tissues of two different patients. SKG-I and SKG-II cells expressed the E6 region of HPV type 18 as mRNAs. These results strongly suggest that the E6 and E7 regions or the sequence surrounding these regions are important for maintaining malignant phenotype of cervical cancer cells.

Cell Line↗
PubMed1987

Stimulation of superoxide anion formation by the non-TPA type tumor promoters palytoxin and thapsigargin in porcine and human neutrophils.

The non-12-O-tetradecanoylphorbol-13-acetate (TPA) type tumor promoters palytoxin and thapsigargin provoked a respiratory burst in porcine and human neutrophils. The amounts of oxygen consumed and superoxide anion (O2-) produced were found to be stoichiometric. Concentrations of 6.5 X 10(-8) M palytoxin and 1.2 X 10(-6) M thapsigargin were required for half-maximal stimulation to 3 X 10(6) porcine cells/ml in Hanks' solution. Combinations of palytoxin and thapsigargin, and of one non-TPA type and one TPA-type tumor promoter, had synergistic effects in stimulating O2- formation in neutrophils, suggesting that these compounds activate the cells by different signal transduction mechanisms.

Acrylamides↗
PubMed1987

Genomic clone of hst with transforming activity from a patient with acute leukemia.

We have previously reported the identification of a novel transforming gene, hst, in DNA samples taken from human stomach cancers and a noncancerous portion of stomach. Five clones, containing the genomic hst gene, were isolated from a human cosmid library constructed from leukocyte DNA from a patient with acute leukemia. All clones possessed transforming activity when transfected to NIH3T3 cells. From one clone, an 8.7 kb BamHI fragment was subcloned into pBR322, and this subclone was active in transforming NIH3T3 cells. This is the first isolation of transformation-competent genomic hst clones directly from a human genomic library, that is, without prior passage through NIH3T3 cells.

Acute Disease↗
PubMed1987

Tumor promoting activity of teleocidin in skin and forestomach of mice initiated transplacentally with 7,12-dimethylbenz(a)anthracene.

Experiments on the effect of transplacental initiation with 7,12-dimethylbenz(a)anthracene (DMBA) and postnatal promotion with teleocidin were carried out in mice. The percentage of tumor-bearing mice among females treated with DMBA transplacentally on day 17 of gestation and postnatally by topical application of teleocidin to the skin of the back was 73.3% in week 30, whereas that among females treated with DMBA on day 10 of gestation and postnatally by topical application of teleocidin was 20.0%. This indicates that teleocidin shows potent tumor promoting activity on mouse skin in a transplacental initiation and postnatal promotion protocol. Furthermore, in the males treated with DMBA transplacentally on day 17 of gestation and given diet containing 0.01% teleocidin postnatally five tumors of the forestomach were found in 5 of 19 effective mice (26.3%) in week 52. One of these five tumors was a squamous cell carcinoma, and the others were papillomas. This indicates that teleocidin also has tumor promoting activity in the forestomach of mice.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1987

Stimulation of arachidonic acid metabolism in rat peritoneal macrophages by thapsigargin, a non-(12-O-tetradecanoylphorbol-13-acetate) (TPA)-type tumor promoter.

The effects of thapsigargin, which is a histamine secretagogue and has recently been found to be a non-(12-O-tetradecanoylphorbol-13-acetate) (TPA)-type tumor promoter in two-stage carcinogenesis using mouse skin, on arachidonic acid metabolism in rat peritoneal macrophages were examined. The release of radioactivity from 3H arachidonic acid-labeled macrophages was increased at doses more than 10 ng/ml. Prostaglandin E2 production was also increased dose-dependently without inducing prominent changes in cell morphology. The potency to stimulate prostaglandin E2 production by thapsigargin was stronger than that by TPA at a dose of 10 ng/ml when measured 6 h after the incubation. HPLC analysis revealed that thapsigargin stimulated the production of lipoxygenase products such as leukotriene B4 and 12-hydroxyeicosatetraenoic acid as well as cyclooxygenase products such as prostaglandin E2 and 6-keto prostaglandin F 1 alpha. Thapsigargin, an analogue of thapsigargin, also stimulated prostaglandin E2 production. The mechanism of the action of thapsigargin was discussed. It was confirmed that the tumor promoters are associated with the activity to stimulate arachidonic acid metabolism irrespective of their type, TPA-type or non-TPA-type.

Animals↗
PubMed1987

Active H-ras and N-ras in rat fibrosarcomas induced by 1,6-dinitropyrene.

The activated oncogenes in rat fibrosarcomas induced by subcutaneous injection of 1,6-dinitropyrene (1,6-DNP), an environmental mutagen-carcinogen, were examined by NIH3T3 cell transfection assay and Southern blot analysis. DNAs from two of eleven fibrosarcomas, 1,6-DNP6 and 1,6-DNP9T, induced transformants which contained rat specific repetitive sequences. Three primary transformants, obtained with DNA from 1,6-DNP6, and two secondary transformants of one of these primary transformants tested, contained rat H-ras. DNA from 1,6-DNP9T; a fourth transplant of 1,6-DNP9, also induced transformants. All the primary transformants with DNA from 1,6-DNP9T, and three secondary transformants of one of them, contained rat N-ras. The DNA from the original tumor, 1,6-DNP9, however, did not give any transformants by several transfection assays. Activation of N-ras oncogene during serial transplantations is discussed.

Animals↗
PubMed1987

Genomic sequence of hst, a transforming gene encoding a protein homologous to fibroblast growth factors and the int-2-encoded protein.

hst is a transforming gene first identified from transformed NIH 3T3 cells that were transfected with DNA of a human stomach cancer. A genomic fragment of hst obtained directly from a human genomic library also has transforming activity. This fragment has a coding sequence identical to that of the hst cDNA prepared from an NIH 3T3 transformant induced by DNA from a stomach cancer. The deduced amino acid sequence of the hst protein is 43%, 38%, and 40% homologous, respectively, to human basic fibroblast growth factor, human acidic fibroblast growth factor, and mouse int-2 protein in selected regions. This suggests that hst encodes a protein related to fibroblast growth factors, which are wide-spectrum mitogens, and to the int-2 protein, a potential oncogene product implicated in murine mammary carcinogenesis.

Amino Acid Sequence↗
PubMed1987

Loss of heterozygosity on chromosomes 3, 13, and 17 in small-cell carcinoma and on chromosome 3 in adenocarcinoma of the lung.

By a molecular genetic approach using polymorphic DNA markers that detect allelic deletion of specific chromosomal regions, we analyzed for possible loss of chromosomal heterozygosity in five different histological types of lung cancers obtained from 47 patients. In small-cell carcinomas, the incidence of allelic deletions at three different chromosomal loci was extremely high; loss of heterozygosity was detected on chromosomes 3p in 7 of 7 patients (100%), 13q in 10 of 11 patients (91%), and 17p in 5 of 5 patients (100%). The deletions at these loci in small-cell carcinomas were observed even in the tumors without any clinical evidence of metastasis. Furthermore, loss of heterozygosity on chromosomes 3p and 13q occurred prior to NMYC amplification and chromosome 11p deletion. Loss of heterozygosity on chromosome 3p was also detected with high frequency in adenocarcinomas [5 of 6 patients (83%)]. Heterozygosity of chromosomes 13q and 17p was lost in 10 of 31 patients (32%) and in 3 of 12 patients (25%), respectively, of lung cancers other than small-cell carcinomas. These results indicate that recessive genetic changes involving sequences on chromosomes 3p, 13q, and 17p may play important roles in the genesis of small-cell carcinoma, and those on chromosome 3p may play an important role in the genesis of adenocarcinoma.

Adenocarcinoma↗
PubMed1987

cDNA sequence of human transforming gene hst and identification of the coding sequence required for transforming activity.

The hst gene was originally identified as a transforming gene in DNAs from human stomach cancers and from a noncancerous portion of stomach mucosa by DNA-mediated transfection assay using NIH3T3 cells. cDNA clones of hst were isolated from the cDNA library constructed from poly(A)+ RNA of a secondary transformant induced by the DNA from a stomach cancer. The sequence analysis of the hst cDNA revealed the presence of two open reading frames. When this cDNA was inserted into an expression vector containing the simian virus 40 promoter, it efficiently induced the transformation of NIH3T3 cells upon transfection. It was found that one of the reading frames, which coded for 206 amino acids, was responsible for the transforming activity.

Amino Acid Sequence↗
PubMed1987

Activated N-ras oncogene in a transformant derived from a rat small intestinal adenocarcinoma induced by 2-aminodipyrido[1,2-a:3',2'-d]imidazole.

DNAs from five intestinal adenocarcinomas induced by 2-aminodipyrido[1,2-a:3',2'-d]imidazole, which is present in broiled fish, were subjected to transfection assay using NIH3T3 cells as recipients. The DNA from only one adenocarcinoma induced a morphologically transformed focus. Rat N-ras sequences were detected in the primary transformant and in three tested secondary transformants. In the activated N-ras oncogene, a G----T transversion at the first letter of codon 12 was detected. The original tumor DNA did not hybridize with the oligonucleotide representing the mutated allele, but did hybridize with the one representing the normal allele. From these data we concluded either that the activation of the N-ras oncogene had occurred during the transfection or that the activated N-ras oncogene had been present in a minor population of cells in the original tumor.

Adenocarcinoma↗
PubMed1987

Induction of oral cavity cancer by 3-diazotyramine, a nitrosated product of tyramine present in foods.

A mutagenic nitrosation product of tyramine, 4-(2-aminoethyl)-6-diazo-2,4-cyclohexadienone (3-diazotyramine, 3-DT) preferentially induced tumors of the oral cavity. Squamous-cell carcinomas of the mucosa of the oral cavity floor developed in 19 out of 28 male F344 rats administered 0.1% 3-DT in their drinking water. Tyramine and nitrite are found at fairly high concentrations in various foods. This demonstration of the carcinogenicity of 3-DT indicates that although the implications of 3-DT for human cancer are not clear, other nitrosable mutagen precursors need to be tested as possible risk factors in human cancer.

Animals↗
PubMed1987

Carcinogenicity in mice of a mutagenic compound, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) from cooked foods.

2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), which is a mutagenic compound present in fried beef and beef extracts, was given orally to CDF1 mice at a concentration of 0.06% in the diet for 84 weeks. Liver tumors were induced in 43% of males and 91% of females fed MeIQx. The incidences of liver tumors in mice of both sexes were significantly higher in groups fed MeIQx than in control groups. The incidences of lung tumors in females fed MeIQx and of lymphomas and leukemias in both sexes fed MeIQx were also significantly higher than in the respective controls.

Animals↗
PubMed1987

Production and characterization of serovar-specific monoclonal antibodies to serovars 4, 8, and 9 of Mycobacterium intracellulare.

Serovar-specific monoclonal antibodies against Mycobacterium avium-Mycobacterium intracellulare-Mycobacterium scrofulaceum complex serovars 4, 8, and 9 were prepared. Nine, four, and one monoclonal antibodies, respectively, to the serovars were prepared by the usual cell fusion technique. All nine monoclonal antibodies to serovar 4 were monospecific for their homologous serovar and reacted with several native glycopeptidolipids (GPLs) and one major deacylated GPL from the homologous serovar. One of the four monoclonal antibodies to serovar 8 seemed to be monospecific for its homologous serovar, but the other cross-reacted with serovar 6 because serovar 6 organisms contain the same components as does the major deacylated GPL from serovar 8. One monoclonal antibody to serovar 9 was monospecific for its homologous serovar and reacted with one of the two major deacylated GPLs from this serovar. These antibody preparations proved useful for serovar identification.

Agglutination Tests↗
PubMed1987

Rat c-raf oncogene activation by a rearrangement that produces a fused protein.

In a previous study, activated rat c-raf was detected by an NIH 3T3 cell transfection assay, and a rearrangement was demonstrated in the 5' half of the sequence of the gene. In the present study, the cDNAs of normal and activated rat c-raf were analyzed. Results showed that the activated c-raf gene is transcribed to produce a fused mRNA, in which the 5' half of the sequence is replaced by an unknown rat sequence. This mRNA codes a fused c-raf protein. The normal and activated c-raf cDNAs were each connected to the long terminal repeat of Rous sarcoma virus and transfected into NIH 3T3 cells. Only the activated form had transforming activity. We conclude that the rearrangement is responsible for the activation of c-raf.

Amino Acid Sequence↗
PubMed1987

Identification of transforming genes as hst in DNA samples from two human hepatocellular carcinomas.

In a DNA-mediated transfection assay using NIH3T3 cells, the DNAs from two out of twelve human hepatocellular carcinomas gave transformants. The transforming gene was identified as hst, which was originally found in DNAs from stomach cancers and a noncancerous portion of stomach mucosa, the putative product being a growth factor. Transcripts were not detected in the original HCC 1 and HCC2 upon Northern blot analysis. The possible mechanisms involved in the hst gene activation are discussed.

Carcinoma, Hepatocellular↗