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Biomedical subjects

T Sugimura

Publications and source records attributed to T Sugimura.

At least 613 records · Page 34Linked to original sources
PubMed1986

Structure of HTLV and its biological function in leukemogenesis of adult T-cell leukemia.

There is a high homology of nucleotide sequence between 3' two-thirds of the X (or pX) regions of human T-cell leukemia virus (HTLV)-I, and of HTLV-II. Monoclonal antibody against p41 coded from X-IV, an open reading frame of X region of HTLV-I, was established. Two proteins coded by Xb, one of the open reading frames in X region of HTLV-II, were newly identified as p24 and p26. The expression of X protein of HTLV-II in the reconstituted mouse embryonal carcinoma cell line, which shows myoblastic morphology, reverted the morphology to that of the original embryonal carcinoma cells. This suggests that the function of X protein is to disturb the regulation of cell lineage determination. Leukemogenesis of adult T-cell leukemia (ATL) is also considered to consist of multisteps, in which HTLV-I constitutes one step, other factors also being involved. Even the role of HTLV-I factor could be similarly played by other factor(s). In agreement with this hypothesis, there are patients with ATL without associated HTLV-I.

Adult↗
PubMed1986

Glycyrrhetic acid inhibits tumor-promoting activity of teleocidin and 12-O-tetradecanoylphorbol-13-acetate in two-stage mouse skin carcinogenesis.

Glycyrrhetic acid suppressed tumor promoter-induced effects in vitro, such as stimulation of 32Pi-incorporation into phospholipids of cultured cells and down-regulation of the epidermal growth factor receptor. Glycyrrhetic acid inhibited the promoting activity of both 12-O-tetradecanoylphorbol-13-acetate (TPA) and teleocidin on skin tumor formation in mice initiated with 7,12-dimethylbenz[a]anthracene (DMBA). The percentage of tumor-bearing mice in the group treated with DMBA plus teleocidin was 88% at week 18, whereas that in the group treated with DMBA plus teleocidin and glycyrrhetic acid (10 mumol/painting) was 6%. Similarly, the percentage of tumor-bearing mice of the group treated with DMBA plus TPA was 97% at week 20, whereas that of the group treated with DMBA plus TPA and glycyrrhetic acid was 40%. Therefore, glycyrrhetic acid was proved to inhibit the activity of two different tumor promoters, teleocidin and TPA, in mouse skin.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1986

Amplifications of both c-Ki-ras with a point mutation and c-myc in a primary pancreatic cancer and its metastatic tumors in lymph nodes.

Activated c-Ki-ras with a point mutation (GGT to CGT) at codon 12, resulting in the substitution of arginine for glycine, was found in DNA from metastatic pancreatic adenocarcinoma in a lymph node. By means of restriction endonuclease length polymorphism with SacI digestion, we were able to demonstrate that the same point mutation of c-Ki-ras was present in the primary tumor and in metastases in lymph nodes. DNA from the normal spleen of the patient did not have this type of point mutation. Moreover, amplifications of 3- to 6-fold of the activated c-Ki-ras and 50-fold of c-myc were found in the primary tumor and the metastases in the two lymph nodes, indicating that point mutation had occurred at a relatively early stage of the tumor development, before amplification of the gene. This is the first clear demonstration of amplification of activated c-Ki-ras accompanied by amplification of c-myc in both primary and metastatic human tumors in vivo.

Base Sequence↗
PubMed1986

Induction of gastric carcinomas in nonhuman primates by N-ethyl-N'-nitro-N-nitrosoguanidine.

N-Ethyl-N'-nitro-N-nitrosoguanidine [(ENNG) CAS: 63885-23-4] was administered to 5 Macaca monkeys (Macaca mulatta and M. irus) at a concentration of 200 or 300 micrograms/ml for 11-26 months in their drinking water. Gastric carcinomas in the pyloric region were observed in all 5 monkeys between experimental months 11 and 38. Histologically, these carcinomas were mainly poorly differentiated adenocarcinomas and signet-ring cell carcinomas, and a few moderately and well-differentiated adenocarcinomas were also found. The macroscopic and histologic appearances of these carcinomas were similar to those in humans.

Adenocarcinoma↗
PubMed1986

Mouse 3T3-L1 cell variants unable to respond to mitogenic stimulation of dihydroteleocidin B: genetic evidence for the synergism of tumor promoters with growth factors.

Dihydroteleocidin B, an indole alkaloid tumor promoter, stimulates confluent, quiescent mouse 3T3-L1 fibroblasts to initiate DNA synthesis and undergo cell division. Using a mitotic shakeoff technique, we have isolated 12 clones of genetic variants which are unable to respond to the mitogenic stimulation of dihydroteleocidin B from a total of 12 million cells. Biochemical characterization of these nonresponsive variants to dihydroteleocidin B revealed that there is no change in the ability to bind [3H]phorbol dibutyrate, the activity of protein kinase C, and the turnover of phosphatidylinositol. The evidence indicates that nonresponsiveness to dihydroteleocidin B is caused by several different lesions, including defects in receptors for insulin or epidermal growth factor and in the postreceptor mechanisms. The evidence also suggests that mitogenic signal transfer via the epidermal growth factor receptor system appears to share a common step with dihydroteleocidin B whereas the signal transfer for insulin seems separate from these. These results suggest that phosphatidylinositol turnover followed by protein kinase C activation alone is not sufficient for mitogenic stimulation and that the coordination of the protein kinase C system with the receptor systems for growth factors may be necessary for "full" mitogenic response.

Animals↗
PubMed1986

Presence of albumin-positive cells in the liver of analbuminemic rats and their increase on treatment with hepatocarcinogens.

The analbuminemic rat is a mutant in which albumin mRNA processing is blocked owing to a seven-base-pair deletion in the 9th intron of the albumin gene. A small amount of albumin is detected in the serum of this rat. Production of serum albumin in the liver of this mutant rat was studied by an immunohistochemical method. The results showed that a few albumin-positive cells were present in the liver of the mutant rat, whereas all the hepatocytes in normal rat liver were albumin-positive. In the mutant the number of albumin-positive cells increased with age: their frequency was 10(-5) at birth and 6 X 10(-3) at 45 weeks of age. On administration of 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) and 2-acetylaminofluorene, albumin-positive cells increased dramatically. Their numbers were 7 to 10 times those of untreated rats after 10 to 16 weeks of carcinogen treatment. The number of albumin-positive cells did not decrease after 3'-Me-DAB feeding was discontinued. In regenerating liver after partial hepatectomy, clusters of albumin-positive cells increased while the number of singlet albumin-positive cells decreased. These observations suggest that the appearance of albumin-positive cells in analbuminemic rat liver may be due to a somatic mutation of the hepatocytes.

2-Acetylaminofluorene↗
PubMed1986

Modulation of phorbol ester receptors in mouse skin by application of quercetin.

The topical application of quercetin, an anti-tumor promoter, to mouse skin reduced the number of phorbol ester receptors, although quercetin did not inhibit specific 3H-12-O-tetradecanoylphorbol-13-acetate binding to a mouse skin particulate fraction. Quercetin, morin, kaempferol and luteolin inhibited activation of protein kinase C by teleocidin, and caused half-maximal activation at 25 microM. (+)-Catechin, which has been reported not to inhibit tumor-promoting activity, did not have any effect on these reactions. The modulation of phorbol ester receptors and inhibition of activation of protein kinase C are considered to be involved in the anti-tumor-promoting effect of quercetin in mouse skin. Diet containing 4% or 1% quercetin did not influence the action of teleocidin on mouse skin in a two-stage carcinogenesis experiment.

Animals↗
PubMed1986

Rearrangement of the c-myc gene in two giant cell carcinomas of the lung.

The c-myc oncogene was found to be rearranged in a human cell line of giant cell carcinoma of the lung (C-Lu65) and in a human primary giant cell carcinoma of the lung (LuC38C). The rearrangements in C-Lu65 and LuC38C were in regions about 7.5 kb and 6 kb, respectively, upstream from the transcription initiation site. No rearrangement of the c-myc gene was observed in a non-cancerous portion (LuC38N) of the lung of the patient who carried LuC38C. These results suggest that rearrangement of the c-myc gene may play some role in tumorigenesis of giant cell carcinoma of the lung.

Carcinoma↗
PubMed1986

Cysteine-rich regions conserved in amino-terminal halves of raf gene family products and protein kinase C.

The predicted amino acid sequences of rat c-raf and A-raf products were subjected to homology search against other known amino acid sequences. We found that characteristic, cysteine-rich regions present in the amino-terminal halves of c-raf and A-raf products had striking homologies with the cysteine-rich regions present in protein kinase C. These cysteine-rich regions had been shown to be deleted in the activated raf products and in the catalytically active protein kinase C produced by proteolysis. These facts suggest the significance of the cysteine-rich regions of raf products as well as those of protein kinase C in the regulation of kinase activities.

Amino Acid Sequence↗
PubMed1986

Activation of rat and human c-raf(-1) by rearrangement.

Activated c-raf(-1) gene was found in three transformants obtained by transfecting DNAs from rat hepatocellular carcinoma, metastasis of human colon cancer in mesocolon and normal mucosa from a different colon cancer patient. Rat and human activated c-raf(-1) genes were cloned into cosmid vectors; restriction enzyme mapping revealed both activated c-raf(-1) genes to have rearrangement in the center of the normal form of the gene, and the upstream sequences were replaced by unrelated sequences. Using genomic DNA fragments located immediately downstream of the recombination points, the activations of all these c-raf(-1) were shown to have occurred during the transfection process. The recombination points in both the rat and human clones isolated were located in the intron between exons 7 and 8, and nucleotide sequencing around these recombination points showed there to be an inverted repeat which could be involved in inducing in vitro recombination. Nucleotide sequencing of rat and human c-raf(-1) cDNAs revealed the upstream sequences, recombined to the 3' half of c-raf(-1), to be expressed as fusion mRNAs; the production of fused proteins was predicted from a long open reading frame, which is in-frame with the kinase domain encoded from the 3' half of the c-raf(-1) gene. There is a cysteine clustering region in an N-terminal region of the c-raf(-1) product deduced from the nucleotide sequence, and this cysteine clustering region was found to be highly homologous to that present in an N-terminal region of protein kinase C, although, in the latter cysteine clusters are present in duplicate. From analogy with the activation mechanism of protein kinase C, the N-terminal region of serine/threonine kinase coded by the c-raf(-1) gene is suggested to be a regulatory part of the enzyme activity, and it proposed that the replacement or truncation of this regulatory part could be the mechanism whereby c-raf(-1) is activated.

Amino Acid Sequence↗
PubMed1986

A novel transforming gene, hst, from human stomach cancers and a non-cancerous portion of stomach mucosa.

DNAs from 21 human stomach cancers, 16 metastatic stomach cancers to lymph nodes, and 21 non-cancerous mucosae of the stomach from a total number of 26 patients with stomach cancer were assayed for their transforming activity to NIH3T3 cells. Three samples of DNA were positive in transfection assay; one was from a primary stomach cancer of one patient (No. 361), the second was from a non-cancerous portion of stomach mucosa of the same patient (No. 363) and the third was from a lymph node metastasis of stomach cancer from another patient (No. 51). A portion of the transforming gene was cloned and a cDNA clone for this gene was isolated. The reading frame essential for the transforming activity was identified. From the results of sequence analysis of cDNA and Southern blot analysis, this transforming gene did not have homology with any oncogene reported previously. We applied the term, hst (human stomach cancer), to this novel transforming gene. This hst gene was not only responsible for acquisition of transforming activity of No. 361 DNA, but also for that of No. 363 and No. 51 DNAs; all the transformants induced by Nos. 361, 363, and 51 DNAs contained hst gene.

Cell Transformation, Neoplastic↗