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81.
82.
2-Deoxy-L-ribose inhibits the invasion of thymidine phosphorylase-overexpressing tumors by suppressing matrix metalloproteinase-9 总被引:1,自引:0,他引:1
Nakajima Y Haraguchi M Furukawa T Yamamoto M Nakanishi H Tatematsu M Akiyama S 《International journal of cancer. Journal international du cancer》2006,119(7):1710-1716
Thymidine phosphorylase (TP), an enzyme involved in pyrimidine metabolism, is identical with an angiogenic factor, platelet-derived endothelial cell growth factor. 2-Deoxy-D-ribose (D-dRib), the degradation product of thymidine generated by TP activity, has been suggested to be a downstream mediator of TP function. 2-Deoxy-L-ribose (L-dRib), a stereoisomer of D-dRib, inhibited the promotion of angiogenesis, tumor growth and metastasis by TP. In our study, we have shown that nude mice inoculated with TP-overexpressing KB/TP cells had shorter survival times than those injected with control KB/CV cells. KB/TP tumors were also more highly invasive than KB/CV tumors in mice. The expression levels of matrix metalloproteinase (MMP)-9 in KB/TP tumors were significantly higher than those in KB/CV tumors. L-dRib and a TP inhibitior, TPI, extended the survival period of KB/TP tumor-bearing mice. L-dRib also reduced MMP-9 mRNA levels in KB/TP tumors. Furthermore, L-dRib suppressed the mRNA level of MMP-9 in cultured KB/TP cells, and the invasive activity of the cells. L-dRib may be useful for the suppression of invasion of TP-expressing tumor cells. 相似文献
83.
Horikoshi T Kikuchi A Matsumoto Y Tatematsu M Takae K Ogiso Y Nakayama M Unno N 《The journal of obstetrics and gynaecology research》2005,31(6):552-555
Abstract We report on a fetus with a congenital pulmonary myofibroblastic tumor, the prenatal detection of which with imaging modalities has not been reported up until now. A 32-year-old woman was referred to our hospital at 29 weeks' gestation because of severe fetal hydrops. Sonograms and magnetic resonance imaging showed a large solid tumor in the left thorax. The fetus died in utero the next day. Autopsy confirmed that the tumor was confined to the lower lobe of the left lung, and circulatory insufficiency from compression by the tumor was considered to be the cause of fetal hydrops and demise. Histologic examination revealed that the tumor was composed of uniform short spindle cells with no atypia and a large number of vessels. In addition, with immunohistochemical studies, the tumor cells were stained for calponin but not for cluster differentiation (CD)-31, CD-34, alpha-smooth muscle actin or S-100. 相似文献
84.
Tatematsu Masae Takahashi Michihito Tsuda Hiroyuki Ogiso Tadashi Ito Nobuyuki 《Toxicology letters》1978,1(4):201-205
The chronic toxicity and carcinogenicity of an antihypertensive agent, reserpine, on oral administration was examined in Wistar strain rats. Male and female rats were given diets containing 0, 30 or 60 ppm of reserpine for 75 weeks. The body weights of male and female rats on diets containing 60 ppm and 30 ppm reserpine were significantly lower (P < 0.001) than those of the controls. Benign and malignant tumors were found, but their incidences were not statistically significant. Moreover, no histopathological changes were found that were significantly related to reserpine administration. 相似文献
85.
Dose responses of five hepatocarcinogens for the initiation of rat hepatocarcinogenesis 总被引:2,自引:0,他引:2
Using the Solt and Farber model (Nature, 263 (1976) 701), dose-response relationships between initiating agents and the induction of hyperplastic nodules in rat liver were investigated. Male Fischer 344 rats were initiated by a single application of 1 of 5 carcinogens at 3 doses: 200.0, 50.0 and 12.5 mg/kg of diethylnitrosamine (DEN); 1.00, 0.25 and 0.062 mg/kg of aflatoxin B1 (Af-B1); 60.0, 15.0 and 3.75 mg/kg of N-2-fluorenylacetamide (2-FAA); 600.0, 150.0 and 37.5 mg/kg of 3'-methyl-4-dimethylaminobenzene (3'-me-DAB); 40.0, 10.0 and 2.5 mg/kg of dimethylnitrosamine (DMN) and their vehicles. Two weeks after initiation, animals were placed on a 0.02% 2-FAA diet for 2 weeks. Partial hepatectomy was performed at the end of the third week of the experiment. All rats were killed 4 weeks after the initiation, and the hyperplastic nodules of the liver were counted and their areas measured. Dose responses were observed in both numbers and areas of hyperplastic nodules per unit area of sections with all of the 5 carcinogens examined. 相似文献
86.
The dose-dependence effects of 3 antioxidants, butylated hydroxyanisole (BHA: 2.0%, 1.0% and 0.5%), butylated hydroxytoluene (BHT: 1.0%, 0.5% and 0.25%) and ethoxyquin (EQ: 0.5%, 0.25% and 0.125%) combined with partial hepatectomy on the development of preneoplastic lesions in the liver of diethylnitrosamine (DEN, 200 mg/kg body wt)-treated rats were investigated. Feeding of the antioxidants commenced 2 weeks after the single dose of DEN used to initiate the lesions. gamma-Glutamyl transpeptidase (gamma-GT) and the placental form of glutathione S-transferase (GST-P) were used for quantitation of altered focal populations. Results with both markers demonstrated a dose-dependent decrease of foci in BHA-treated rats relative to those in control rats. Morphometric analysis of gamma-GT-positive lesions also revealed decrease in both the number and area of foci in BHT- and EQ-treated groups. The discrepancy between results of quantitation of gamma-GT- and GST-P-positive foci was attributable to the induction of a background, periportal zone staining for gamma-GT, which made differentiation of smaller foci difficult. Comparison of results with the 2 markers suggested that GST-P is the more accurate marker for quantitative studies on enzyme altered foci in rat liver. 相似文献
87.
Fukushima S Wanibuchi H Morimura K Nakae D Tsuda H Imaida K Shirai T Tatematsu M Tsukamoto T Hirose M Furukawa F 《Cancer letters》2005,222(1):11-15
Induction of liver lesions in male F344 rats by the genotoxic and carcinogenic N-nitrosodimethylamine (NDMA) was studied at a wide range of dose levels, i.e. from 0.001 to 10 ppm, in drinking water for 16 weeks. Dose related and statistically significant increase of glutathione S-transferase placental form-positive foci, endpoint markers for hepatocarcinogenesis in rats, at 1 and 10 ppm dose groups was obtained, but no increment in foci could be detected with the lower doses (0.001, 0.01, and 0.1 ppm). This finding of a no-observed effect level supports our hypothesis that a threshold, at least in practical terms, exists in carcinogenesis proposed on the basis of extensive wide range dose-dependence studies of other genotoxic carcinogens. 相似文献
88.
Asaoka Y Sakai H Takahashi N Hirata A Tsukamoto T Yamamoto M Yanai T Masegi T Tatematsu M 《Journal of applied toxicology : JAT》2005,25(6):554-561
In an in vivo 5-week initiation assay model, chemical hepatectomy by hepato-toxicant administration was utilized as a cell proliferation stimulus as an alternative to the two-thirds partial hepatectomy. The study investigated the effect of an intraperitoneal (i.p.) injection of D-galactosamine (D-gal) for this purpose in a medium-term liver bioassay, with a further focus on cell proliferation kinetics and cytochrome P450 (CYP) expression. In experiment I, cell proliferation in rat liver after a single administration of D-gal (700 mg kg(-1), i.p.) was analysed by the bromodeoxyuridine (BrdU) labeling method, and CYP isozymes were quantified by immunoblotting. In experiment II, the induction of glutathione S-transferase placental form (GST-P) positive foci by 1,2-dimethylhydrazine (DMH) was evaluated in a modified in vivo 5-week initiation assay model. At 84 hours after single administration of d-gal (i.p.) the BrdU index was markedly elevated (27.5% +/- 9.5%). Although CYP 2E1 and 1A2 apoprotein contents decreased transiently to less than 20% of the control level, subsequently they recovered to 60% and 40% of the control level, respectively, at 84 hours. Induction of GST-P positive foci in the group given DMH at 84 hours after a single administration of d-gal was significantly greater than in the control group, correlating with the kinetics of cell proliferation. In conclusion, the sensitivity of the present initiation assay using D-gal i.p. is high, so that D-gal i.p. can be considered an effective cell proliferation stimulus. 相似文献
89.
90.
Ken-ichi Inada Hayao Nakanishi Yasunobu Fujimitsu Nobuyuki Shimizu Masao Ichinose Kazumasa Miki Shigeo Nakamura Masae Tatematsu 《Pathology international》1997,47(12):831-841
To generate a novel understanding of Intestinal metaplasia (IM) on the basis of cellular differentiation status, a total of 132 gastric surgical specimens were studied using gastric and small intestinal cell markers by much histochemical and Immunohistochemical techniques. The cases were divided into two types: (i) gastric and intestinal (GI) mixed type; and (ii) solely intestinal (I) type, with the reference to the presence of gastric and/or intestinal cell markers. The GI mixed type was subdivided into six subtypes: (i) a subtype consisting of surface mucous (Su), pyloric gland (Py), Intestinal absorptive (Ab), and goblet (Go) cells, but lacking Paneth (Pa) cells, GI(Pa-); (ii) a GI(Pa-) subtype without Py cells, GI(Py-, Pa-); (iii) a GI(Pa-) subtype without Su cells, GI(Su-, Pa-); (iv) a GI(Su-, Pa-) subtype with Pa cells, GI(Su-, Pa+); (v) a Gi(Pa-) subtype with Pa cells, GI(Pa+); and (vi) a GI(Pa+) subtype without Py cells, GI(–, Pa+).The I type was subdivided Into: (I) a subtype consisting of cells with Ab and Go cells, I(Pa-); and (ii) a I(Pa-) subtype with Paneth cells, I(Pa+). The GI mixed subtypes, except for the GI(Py-, Pa-) and GI(Py-, Pa+), were characterized by Intestinalized gastric plts connected with underlying pyloric glands. Immunohistochemical staining of proliferating cell nuclear antigen (PCNA) revealed a common prolifemtive cell zone between the two. The GI mixed type, especially the GI(Pa-) subtype, predominated in the pyloric mucose, while the I type was most frequent In the fundle region, suggesting that the pathogenesis of IM differs between these two locations. The results of the study confirm that IM is an abnormal and unstable differentiation status between the stomach and small Intestine. 相似文献