PubMed Health⌕ Search

Biomedical subjects

T Sugimura

Publications and source records attributed to T Sugimura.

At least 433 records · Page 24Linked to original sources
PubMed1990

Calyculin A, an inhibitor of protein phosphatases, a potent tumor promoter on CD-1 mouse skin.

Calyculin A, isolated from a marine sponge, has a novel spiro ketal skeleton. Structurally unrelated to okadaic acid, calyculin A bound to the okadaic acid receptors in particulate and soluble fractions of mouse skin. The biochemical and tumor-promoting activities of calyculin A were studied with those of okadaic acid. Calyculin A inhibited the activity of protein phosphatases, which serve as the okadaic acid receptors. The effective dose of calyculin A for 50% inhibition was 0.3 nM, similar to that of okadaic acid. Like okadaic acid, calyculin A induced ornithine decarboxylase in mouse skin and hyperphosphorylation of a Mr 60,000 protein in human papilloma virus type 16-transformed human keratinocytes. A two-stage carcinogenesis experiment on mouse skin, initiated by 100 micrograms (390 nmol) of 7,12-dimethylbenz(a)anthracene and followed by 1 microgram (1.0 nmol) of calyculin A, revealed that calyculin A is an additional member of the okadaic acid class of tumor promoters. The percentages of tumor-bearing mice in the groups treated with DMBA plus calyculin A, and with DMBA followed by 1 microgram (1.2 nmol) of okadaic acid were 86.7 and 80.0%, respectively, in week 30. The mechanisms of action of calyculin A and okadaic acid, in addition to dinophysistoxin-1 (35-methylokadaic acid), are discussed. Calyculin A is the first tumor promoter to be screened by the okadaic acid receptor binding test.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1990

cDNA cloning and characterization of ret activated in a human papillary thyroid carcinoma cell line.

We obtained activated ret cDNAs (retTPC) from a human papillary thyroid carcinoma cell line, TPC-1, and characterized its structure. The nucleotide sequence indicated that the recombination had occurred just upstream of the kinase domain of ret proto-oncogene and that the position, where the conserved sequence of ret proto-oncogene starts in retTPC transcripts, was exactly the same as that of ret-II which we have previously analyzed. Furthermore, a unique 13-glycine stretch, which is also present in a small subunit of the calcium dependent protease, calpain, was detected in the replaced sequence of retTPC. The aberrant tyrosine kinase activity induced by the rearrangement of ret proto-oncogene could be involved in the development of papillary thyroid carcinoma.

Amino Acid Sequence↗
PubMed1990

Characterization of a putative promoter region of the human poly(ADP-ribose) polymerase gene: structural similarity to that of the DNA polymerase beta gene.

The 5'-flanking region of the human poly(ADP-ribose) polymerase gene was isolated and characterized. The nucleotide sequence of a part of the poly(ADP-ribose) polymerase gene completely matched that of the cDNA. The transcriptional initiation sites (cap sites) of this gene, located about 166-bp upstream from the translational initiation site, were identified by S1 mapping analysis. Neither CAAT box nor TATA box was found within 500-bp upstream from the cap sites of poly(ADP-ribose) polymerase gene. The 200-bp immediately upstream of the cap site had a high G+C content (76.5%) and contained double repeats of the sequence CCGCCC, putative Sp1 binding sites, and a palindromic structure. The 5'-flanking region of poly(ADP-ribose) polymerase gene also showed promoter activity in chloramphenicol acetyltransferase assay and structural similarity to that of DNA polymerase beta gene.

Base Sequence↗
PubMed1990

Human papillomavirus DNA in squamous cell carcinoma of the upper aerodigestive tract.

Nineteen samples of DNA from squamous cell carcinoma of the upper aerodigestive tract were analyzed by Southern blot hybridization for the presence of human papillomavirus (HPV) DNA. Two samples of DNA contained HPV 16 DNA or its homologous sequence. In one maxillary carcinoma, the sequences homologous to HPV 16 were detected. In one tonsillar carcinoma, HPV 16 sequence was also shown to be present. The patients positive for HPV DNA were female and had neither smoking nor drinking habits. These results indicate that HPV infections may play a role in the development of some types of squamous cell carcinomas of the upper aerodigestive tract.

Adult↗
PubMed1990

Molecular biology of the hst-1 gene.

The hst-1 gene (or HSTF1 by human gene nomenclature) was originally identified in our laboratory by an NIH/3T3 focus formation assay using DNA from a human gastric cancer. Sequence analysis predicted the hst-1 product to be a novel growth factor with 30-50% homology with six other heparin-binding growth factors: basic and acidic fibroblast growth factors (FGFs), the int-2 protein, FGF5, the hst-2/FGF6 protein and keratinocyte growth factor (KGF). A recombinant hst-1 protein was synthesized in silkworm cells and found to be a potent heparin-binding mitogen for murine fibroblasts and human vascular endothelial cells. Although hst-1 expression cannot be detected in most cancer cells, including gastric cancers, it is expressed in mouse embryos and in some germ cell tumours. Both hst-1 and int-2 are located on band q13.3 of human chromosome 11 within a distance of 35 kbp; in the mouse genome these two genes are separated by less than 20 kbp. They are differentially transcribed in the F9 mouse teratocarcinoma cell line; hst-1 is expressed in undifferentiated stem cells and int-2 in differentiated endodermal cells. The hst-1 and int-2 genes were coamplified in a variety of cancer cells, most notably in more than 50% of oesophageal cancers.

Amino Acid Sequence↗
PubMed1990

Okadaic acid, a potent inhibitor of type 1 and type 2A protein phosphatases, activates cdc2/H1 kinase and transiently induces a premature mitosis-like state in BHK21 cells.

When BHK21 cells synchronized in early S phase were exposed to okadaic acid (OA), an inhibitor of protein phosphatases 1 and 2A, mitosis specific events such as premature chromosome condensation, the production of MPM-2 antigens, dispersion of nuclear lamins and the appearance of mitotic asters were induced, and then disappeared upon further incubation. These mitosis specific events occurred even in the presence of cycloheximide. Within 1 h of exposure to OA, cdc2/histone H1 kinase activity rose 10-fold compared with untreated controls, but returned to the control level upon further incubation. Using antibodies against either p34cdc2 or cyclin B it was found that p34cdc2 complexed with cyclin B was dephosphorylated after OA treatment concomitant with the activation of cdc2 kinase, and that cyclin B was subsequently degraded concomitant with a decrease in cdc2 kinase activity, as in normal mitosis. In contrast, when cells in G1 phase were treated with OA no increase in cdc2 kinase activity was observed. Moreover when cells in pseudo-metaphase induced by nocodazole were treated with OA, cdc2 kinase was inactivated. These results suggest that OA sensitive protein phosphatases control both the activation and inactivation of the p34cdc2 kinase.

Animals↗
PubMed1990

New antitumor promoters: (-)-epigallocatechin gallate and sarcophytols A and B.

EGCG, the main constituent of green tea, and sarcophytols A and B, isolated from a soft coral, inhibited tumor promotion by teleocidin in a two-stage carcinogenesis experiment on mouse skin. EGCG and sarcophytols showed inhibition of tumor development by chemical carcinogenesis. A possibility of developing these compounds as cancer chemopreventives for human beings is discussed.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1990

Presence of human papillomavirus type-6-related sequences in inverted nasal papillomas.

Twenty DNA samples obtained from seven cases of inverted papillomas, eight cases of nasal polyps and five cases of chronic sinusitis were investigated by Southern blot hybridization for the possible presence of sequences homologous to human papillomavirus (HPV) types 6, 11, 16 and 18. HPV type-6-related DNA was identified in one of the seven inverted papillomas. The restriction endonuclease cleavage patterns showed that this latter DNA is a new subtype of HPV type 6 DNA. In the other six papillomas and in all cases of nasal polyps and chronic sinusitis, no HPV sequence could be demonstrated, even under low stringent conditions (Tm-40 degrees C). These results indicate that HPV infection might be one of the possible causative factors in the pathogenesis of inverted papillomas but is not essential for the induction of the tumor.

Aged↗
PubMed1990

Gastric carcinogenesis: diet as a causative factor.

Gastric cancer is a very typical cancer related to life styles, including nutrition and dietary conditions. Cigarette smoking has also been pointed out as an enhancing factor in gastric cancer development. Improvement of dietary conditions, regular dietary habits including lower salt, nitrite and nitrite intake and balanced nutritious food may be factors suppressing the incidence of gastric cancer. At the same time, advances in technology for early diagnosis and early surgical treatment have elevated the cure rate of gastric cancers. From both primary and secondary cancer prevention aspects, gastric cancer is now a conquerable disease.

Animals↗
PubMed1990

N-2 acetylation of 2'-deoxyguanosine by coffee mutagens, methylglyoxal and hydrogen peroxide.

Coffee shows direct-acting mutagenicity in Salmonella typhimurium TA100 and most of this mutagenicity is due to the synergistic effects of methylglyoxal and hydrogen peroxide. The modifications of deoxyribonucleosides by methylglyoxal plus hydrogen peroxide were studied in vitro. When 2'-deoxyguanosine (6.25 mumole) was treated with methylglyoxal (125 mumole) and hydrogen peroxide (125 mumole) in 5 ml of 0.1 M phosphate buffer (pH 7.4) at 37 degrees C for 3 h, N2-acetyl-2'-deoxyguanosine was formed with a yield of 1.1%. Its formation increased time-dependently. By contrast, no appreciable modification of other deoxynucleosides was detected after their incubation with methylglyoxal and hydrogen peroxide under similar conditions. N2-Acetyl-2'-deoxyguanosine was also formed during incubation of 2'-deoxyguanosine with instant coffee.

Acetylation↗
PubMed1990

K-sam, an amplified gene in stomach cancer, is a member of the heparin-binding growth factor receptor genes.

DNA fragments amplified in a stomach cancer-derived cell line, KATO-III, were previously identified by the in-gel DNA renaturation method, and a 0.2-kilobase-pair fragment of the amplified sequence was subsequently cloned. By genomic walking, a portion of the exon of the gene flanking this 0.2-kilobase-pair fragment was cloned, and the gene was designated as K-sam (KATO-III cell-derived stomach cancer amplified gene). The K-sam cDNAs, corresponding to the 3.5-kilobase K-sam mRNA, were cloned from the KATO-III cells. Sequence analysis revealed that this gene coded for 682 amino acid residues that satisfied the characteristics of the receptor tyrosine kinase. The K-sam gene had significant homologies with bek, FLG, and chicken basic fibroblast growth factor receptor gene. The K-sam gene was amplified in KATO-III cells with the major transcript of 3.5-kilobases in size. This gene was also expressed in some other stomach cancer cells, a small cell lung cancer, and germ cell tumors.

Amino Acid Sequence↗
PubMed1990

Allele loss on chromosome 16 associated with progression of human hepatocellular carcinoma.

Loss of heterozygosity on chromosome 16 is a common genetic alteration in human hepatocellular carcinoma (HCC). To clarify the pathogenetic significance of allele loss on chromosome 16, we performed restriction fragment length polymorphism analysis of 70 surgically resected tumors by using 15 polymorphic DNA markers for chromosome 16. Loss of heterozygosity on chromosome 16 was detected in 36 (52%) of 69 informative cases, and the common region of allele loss in these 36 tumors was located between the HP locus (16q22.1) and the CTRB locus (16q22.3-q23.2). These losses occurred more frequently in HCCs of poor differentiation, of larger size, and with metastasis, whereas they were not detected in HCC at the earliest stage. In addition, these losses were not associated with presence or absence of hepatitis B virus DNA integration or hepatitis C virus infection. These results show that loss of heterozygosity on chromosome 16 is a late event occurring after hepatocarcinogenesis and strongly suggest that this phenomenon is involved in enhancement of tumor aggressiveness during progression of HCC.

Alleles↗
PubMed1990

Molecular cloning of the human hepatitis C virus genome from Japanese patients with non-A, non-B hepatitis.

The nucleotide sequence of the Japanese type of hepatitis C virus (HCV-J) genome, consisting of 9413 nucleotides, was determined by analyses of cDNA clones from plasma specimens from Japanese patients with chronic hepatitis. HCV-J genome contains a long open reading frame that can encode a sequence of 3010 amino acid residues. Comparison of HCV-J with the American isolate of HCV showed 22.6% difference in nucleotide sequence and 15.1% difference in amino acid sequence. Thus HCV-J and the American isolate of HCV are probably different subtypes of HCV. The relationship of HCV-J with other animal RNA virus families and the putative organization of the HCV-J genome are discussed.

Amino Acid Sequence↗
PubMed1990

Formation of a nitro derivative of 2-amino-3,4-dimethylimidazo[4,5-f]quinoline by photo-irradiation.

A direct-acting mutagen to Salmonella typhimurium TA98 was found to be formed by exposing 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) in acetone to sunlight for 60 min. The direct-acting mutagen in the irradiated sample was purified by HPLC and identified as 3,4-dimethyl-2-nitroimidazo-[4,5-f]quinoline (NO2-MeIQ). The yield of NO2-MeIQ from MeIQ was estimated to be 0.3%.

Chromatography, High Pressure Liquid↗
PubMed1990

Early gastric cancer induced by N-ethyl-N'-nitro-N-nitrosoguanidine in a cynomolgus monkey six years after initial diagnosis of the lesion.

A signet ring cell carcinoma in the gastric antrum of a Cynomolgus monkey induced by N-ethyl-N'-nitro-N-nitrosoguanidine was sequentially studied by endoscopy, biopsy, and autopsy. The carcinoma was first detected on the angulus of the stomach at the 38th month as a slightly elevated lesion. Sixty-one months later this tumor was found to be still in the "early" (intramucosal) stage. Another, independent, initial gastric cancer was also discovered. This is the first example of an induced gastric carcinoma remaining in the "early" stage during a six-year follow-up period after the initial histologic diagnosis.

Adenocarcinoma, Mucinous↗