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Biomedical subjects

A Komori

Publications and source records attributed to A Komori.

At least 55 records · Page 3Linked to original sources
PubMed1993

Tumor necrosis factor acts as a tumor promoter in BALB/3T3 cell transformation.

Tumor necrosis factor (TNF), a cytokine, and okadaic acid, a tumor promoter, strongly phosphorylated the same proteins, vimentin and heat shock protein 27, although their time courses were different. Human TNF-alpha at a concentration of 0.6 nM markedly stimulated transformation of BALB/3T3 cells initiated with 3-methylcholanthrene. The human TNF-alpha was about 1000 times more effective than the chemical tumor promoters, okadaic acid and 12-O-tetradecanoylphorbol-13-acetate. TNF induced growth of v-Ha-ras transfected BALB/3T3 cells (Bhas 42 cells), whereas it did not induce growth of nontransfected BALB/3T3 cells. Okadiac acid induced mouse TNF-alpha from Bhas 42 and BALB/3T3 cells. The results suggest that a chemical tumor promoter induces the secretion of TNF-alpha from various cells. The TNF then acts as an endogenous tumor promoter in vivo.

3T3 Cells↗
PubMed1993

Hyperphosphorylation of cytokeratins by okadaic acid class tumor promoters in primary human keratinocytes.

Okadaic acid, dinophysistoxin-1 (35-methylokadaic acid), and calyculin A are potent tumor promoters on mouse skin (H. Fujiki, M. Suganuma, S. Nishiwaki, S. Yoshizawa, J. Yatsunami, R. Matsushima, H. Furuya, S. Okabe, S. Matsunaga, and T. Sugimura. In: R. D'Amato, T. J. Slaga, W. Farland, and C. Henry (eds.), Relevance of Animal Studies to the Evaluation of Human Cancer Risk, pp. 337-350. New York: John Wiley and Sons, Inc., 1992). These tumor promoters, which are also inhibitors of protein phosphatases 1 and 2A, induced hyperphosphorylation of M(r) 60,000, M(r) 58,000, M(r) 56,000, M(r) 52,000, M(r) 42,000, and M(r) 27,000 proteins in PHK 16-I cells, human keratinocytes immortalized by human papillomavirus type 16. Except for the M(r) 27,000 protein, these hyperphosphorylated proteins were identified to be cytokeratin peptides (CK) CK 5, CK 6, CK 7, CK 16, and CK 19, by anti-cytokeratin antibodies. CK 5 and CK 6 were more strongly phosphorylated than CK 16 and CK 19. The in vitro hyperphosphorylation of these cytokeratins was also found by incubation with an enzyme fraction containing a mixture of protein phosphatase 2A and protein kinases isolated from mouse brain and various concentrations of dinophysistoxin-1. Indirect immunofluorescence microscopy with anti-cytokeratin antibodies revealed that the hyperphosphorylated cytokeratins had retracted to the perinuclear area. The hyperphosphorylated M(r) 27,000 protein was identified as a heat shock protein, HSP27. Hyperphosphorylation of HSP27 and intermediate filaments, such as cytokeratins, is one of the early biochemical changes, or pleiotropic effects, in cells induced by the okadaic acid class of tumor promoters.

Blotting, Western↗
PubMed1993

Hyperphosphorylation of retinoblastoma protein and p53 by okadaic acid, a tumor promoter.

A potent tumor promoter, okadaic acid, induced hyperphosphorylation of tumor suppressor proteins, retinoblastoma protein and p53, by in vitro incubation with nuclei isolated from rat regenerating liver as well as by incubation with primary human fibroblasts. Most of the retinoblastoma protein migrated to a hyperphosphorylated position in electrophoresis. The phosphorylation of p53 was increased at a rate 8 times that in non-treated primary human fibroblasts. Hyperphosphorylation of tumor suppressor proteins, mediated through inhibition of protein phosphatases 1 and 2A, is involved in tumor promotion by okadaic acid. The significance of hyperphosphorylation of the retinoblastoma protein and p53 is discussed in relation to the regulation of the cell cycle.

Animals↗
PubMed1993

Effects of rapamycin in experimental organ allografting.

The immunosuppressive effect of rapamycin (RAPA), a macrolide antibiotic produced by Streptomyces hygroscopicus, was tested using allografts in the rat and dog. It was immunosuppressive at a dose of 3.0 mg/kg/day for 8 days in skin allografts and 0.1 mg/kg/day for 11 days using cardiac allografts in the rat. It prevented rejection of renal allografts in beagle dogs at a dose of 0.3 mg/kg; however, emaciation and gastrointestinal toxicity resulted in some deaths in dogs. Mucosal necrosis and vasculitis in the submucosal layer were the predominant findings at autopsy in dogs receiving RAPA. Serum amylase values rose soon after commencement of RAPA treatment. Combined drug treatment with CsA at a nonimmunosuppressive dose of 3.2 mg/kg in the rat or 2.5 mg/kg in the dog was synergistic, with a low dose of 0.1 mg/kg/week RAPA. Combined therapy of CsA and RAPA also inhibited the frequency of vasculitis and emaciation in dogs. The present data suggest that RAPA is immunosuppressive in organ allografting and that the combination of CsA and RAPA would be effective clinically.

Animals↗
PubMed1993

Anticarcinogenic activity of green tea polyphenols.

The main physiologically active polyphenol in green tea extract is (-)-epigallocatechin gallate (EGCG). Green tea extract has an advantage over EGCG as a cancer chemopreventive agent for humans, as is apparent from the Japanese custom of injesting green tea on a daily basis. Green tea extract similarly inhibited protein kinase C activation by teleocidin, a tumor promoter, as did EGCG. In addition, EGCG and green tea extract showed inhibitory effects on the growth of lung and mammary cancer cell lines with similar potencies. An experiment using the estrogen-dependent MCF-7 cell line showed the mechanisms of action of these compounds to be inhibiting the interaction of estrogen with its receptors. Considering our previous results of a single application of EGCG to mouse skin inhibiting the specific binding of 3H-12-0-tetradecanoylphorbol-13-acetate (3H-TPA) and 3H-okadaic acid, we postulated that EGCG and compounds in green tea extracts would block the interaction of tumor promoters, hormones and growth factors with their receptors: a kind of sealing effect. The sealing effect would account for reversible growth arrest, and may be induced by various kinds of compound.

Animals↗
PubMed1992

Hyperphosphorylation of cytokeratins 8 and 18 by microcystin-LR, a new liver tumor promoter, in primary cultured rat hepatocytes.

Microcystin-LR (MC-LR), an inhibitor of protein phosphatases 1 and 2A, is a potent tumor promoter in rat liver initiated with diethylnitrosamine. To understand its biochemical process in hepatocytes, primary cultured rat hepatocytes were treated with MC-LR. MC-LR (1 microM) induced phosphorylation of various proteins. Two 55 and 49 kDa proteins were phosphorylated at a 3-fold higher rate than other proteins, and these proteins were identified to be cytokeratins 8 and 18 respectively, by immunoprecipitation and Western blot analysis using monoclonal anti-cytokeratin 8 and 18 antibodies. The basic cytokeratins 8 and 18 showed pI 6.4 and 5.4 respectively, in two-dimensional gel electrophoresis. MC-LR dose dependently increased phosphorylation of cytokeratins 8 and 18 in a cell-free system by incubation with a cytosolic fraction of rat liver containing both protein kinases and protein phosphatases 1 and 2A, and with [gamma-32P]ATP. Cytokeratins 8 and 18 were target proteins for phosphorylation induced by inhibition of protein phosphatases 1 and 2A, in vitro and in rat hepatocytes. Thus, the treatment of rat hepatocytes with MC-LR induced hyperphosphorylation of cytokeratins 8 and 18 associated with morphological changes, indicating that intermediate filament networks were rearranged in the cytoplasm. The hyperphosphorylation of cytokeratins is a significant biochemical process associated with liver tumor promotion.

Animals↗
PubMed1992

Marine natural products against tumor development.

This review article deals with significant effects of marine natural products in carcinogenesis, namely as chemical probes to understand the process of carcinogenesis and as possible cancer preventive agents in humans.

Amphibian Proteins↗
PubMed1991

Mechanism of action of newly developed vitamin D analogue.

26,27-F6-1,25(OH)2D3 has a higher potency both in vivo and in vitro systems, and longer duration of action in vivo, instead of almost equal binding to 1,25(OH)2D3 receptor and comparatively short serum half-life. To date, the mechanism of higher action is not known, but using these analogues as a mirror we might be able to elucidate the mechanism of action or the metabolism of the kidney hormone, 1,25(OH)2D3.

Animals↗
PubMed1987

Osteosarcoma mimicking fibrous dysplasia of the jaw.

An unusual case of osteosarcoma of the jaw in a 53-year-old man is reported. The tumor primarily occurred in the right maxilla, and spread to the right mandible. Finally, the patient died of an intracranial extension of the tumor after about 4 years. Microscopically, the tumor was well-differentiated osteosarcoma, but was suspected at first to be fibrous dysplasia.

Diagnosis, Differential↗
PubMed1986

Focal lymphocytic infiltration in the human labial salivary glands: a postmortem study.

Focal lymphocytic infiltration in the human labial salivary glands was examined in a series of 190 postmortem subjects after suitable exclusion had been made. Focal lymphocytic infiltration, with or without a slight degree of parenchymal atrophic change, was found in 22.4% of the males and in 35.7% of the females. Of these, 9.0% (12 subjects) of the males and 10.7% (6 subjects) of the females with focal lymphocytic infiltration did not show any atrophic changes of the parenchyma. In the series reported here, the prevalence of focal lymphocytic infiltration apparently differs from the results of earlier investigators who had reported that none of the postmortem subjects without autoimmune diseases or connective tissue diseases showed focal lymphocytic infiltration in minor salivary glands. Although the pathological significance of focal lymphocytic infiltration in the minor salivary glands remains obscure, its diagnostic value for Sjögren's syndrome is discussed.

Adult↗
PubMed1984

Central intravascular papillary endothelial hyperplasia of the mandible.

Light and electron microscopic findings in papillary endothelial hyperplasia of the mandible in a 49-year-old female are reported. The endothelial cell-lined papillary projection into a cystic lumen was examined by light microscopy and characteristic features of the endothelial cells were found by electron microscopy. Factor VIII-related antigen was demonstrated in the endothelial cells by the immunoperoxidase technique.

Antigens↗