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OBJECTIVES: Oral hairy leukoplakia (HL) is an acan-thotic, hyperparakeratotic lesion characterised by the presence of a replicative Epstein-Barr virus (EBV) infection in the superficial and adjoining layers of the epithelium. EBV or its gene products are capable of modifying epithelial differentiation. The aim of this study was to establish whether the presence of EBV was associated with an alteration in cell turnover by assessing bromodeoxyuridine (BrdU) incorporation and Ki 67 expression in lesional tissue and control mucosa.
METHODS: Biopsies of HL together with age, site and sex matched controls ( n = 7 and 8 respectively) were incubated in 200 μM BrdU in vitro , fixed in methacarn and processed to paraffin wax. Following acid hydrolysis, incorporated BrdU and Ki 67 were identified in serial 5 fim sections using a three-stage immunoperoxidase technique and cell density expressed as the number of positive cells per mm basement membrane length.
RESULTS: Overall, there was no difference in the number of BrdU positive cells per mm basement membrane length between control and HL tissue. However, within HL alone, the presence'of focal EBV replication was associated with a significant reduction in the number of basal cells incorporating BrdU compared to adjacent EBV free areas (P < 0.05). There was no significant difference between Ki 67 positive cells in control and HL tissue and no evidence of a reduction of Ki 67 positive cells in areas associated with EBV replication.
CONCLUSIONS: These results suggest that there is no evidence of a generalised alteration of the proliferative capacity of basal cells in HL, although the focal reduction in BrdU incorporation may reflect subtle changes on cell turnover by EBV infection. 相似文献
METHODS: Biopsies of HL together with age, site and sex matched controls ( n = 7 and 8 respectively) were incubated in 200 μM BrdU in vitro , fixed in methacarn and processed to paraffin wax. Following acid hydrolysis, incorporated BrdU and Ki 67 were identified in serial 5 fim sections using a three-stage immunoperoxidase technique and cell density expressed as the number of positive cells per mm basement membrane length.
RESULTS: Overall, there was no difference in the number of BrdU positive cells per mm basement membrane length between control and HL tissue. However, within HL alone, the presence'of focal EBV replication was associated with a significant reduction in the number of basal cells incorporating BrdU compared to adjacent EBV free areas (P < 0.05). There was no significant difference between Ki 67 positive cells in control and HL tissue and no evidence of a reduction of Ki 67 positive cells in areas associated with EBV replication.
CONCLUSIONS: These results suggest that there is no evidence of a generalised alteration of the proliferative capacity of basal cells in HL, although the focal reduction in BrdU incorporation may reflect subtle changes on cell turnover by EBV infection. 相似文献
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Yuki Hayata Hayato Nakagawa Shigeyuki Kurosaki Satoshi Kawamura Yuki Matsushita Yoku Hayakawa Nobumi Suzuki Masahiro Hata Mayo Tsuboi Hiroto Kinoshita Koji Miyabayashi Hiroya Mizutani Ryo Nakagomi Tsuneo Ikenoue Yoshihiro Hirata Junichi Arita Kiyoshi Hasegawa Keisuke Tateishi Kazuhiko Koike 《Gastroenterology》2021,160(6):2133-2148.e6
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维生缺B1缺乏对成体室管膜下神经发生的影响 总被引:1,自引:1,他引:0
目的:探讨维生缺B1缺乏(TD)对成年小鼠室管膜下区(SVZ)神经发生的影响。方法:TD小鼠模型按TD喂食时间分为TD7、TD14和TD21d组,正常对照组(Con)小鼠则按标准喂食及时间亦分为Con7、Con14和Con21d组(每组n=6)。小鼠处死前5d腹腔给予5-溴脱氧尿嘧啶核苷(BrdU)。用免疫荧光组化染色分别检测SVZ的BrdU和微管相关蛋白(Dcx)阳性细胞的分布和数目。结果:正常组的BrdU阳性细胞和Dcx阳性细胞在SVZ均匀分布在侧脑室背外侧角,侧脑室外侧壁亦有少量分布,TD14和TD21d组两类阳性细胞的减少主要为侧脑室背外侧角。在TD14和TD2Id组,室管膜下区BrdU标记阳性细胞数(像素/mm^2值分别为74.97±7.75和67.27±10.91)明显低于对照组(像素/mm^2值分别为122.30±8.86和122.99±5.33),Dcx标记阳性细胞数(像素/mm^2值分别为1485.98±163.21和935.73±273.66)也明显低于对照组(像素/mm^2值分别2359±155.68和2355±100.75)。结论:TD可阻碍成年小鼠SVZ的神经发生。 相似文献
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Effects of melatonin on proliferation of cancer cell lines 总被引:1,自引:0,他引:1
Konstantinos T. Papazisis Demetrios Kouretas George D. Geromichalos Efthimios Sivridis Olga K. Tsekreli Konstantinos A. Dimitriadis Alexander H. Kortsaris 《Journal of pineal research》1998,25(4):211-218
Papazisis KT, Kouretas D, Geromichalos GD, Sivridis E, Tsekreli OK, Dimitriadis KA, Kortsaris A.H. Effects of melatonin on proliferation of cancer cell lines. J. Pineal Res. 1998; 25:211–218. © Munksgaard, Copenhagen The pineal hormone melatonin has been reported to have in vitro antiproliferative effects on estrogen receptor-positive human breast cancer cell lines at concentrations near to plasma physiological concentrations (1 times 10-11 to 1 times 10-9 M). Its growth inhibitory actions have been thought to be linked to the estrogen-receptor system. We tested the cytotoxic effects of melatonin on MCF-7 and T47D human breast cancer cell lines by using the SRB (sulforhodamine-B), XTT-tetrazolium, and bromodeoxyuridine (BrdU) assays in 96-well microtiter plates. After a 3 or 4 day exposure, melatonin did not have any significant effect on breast cancer cell proliferation and survival in doses up to 1 times 10-4 M. Doses higher than 1 mM exhibited a potent cytotoxic effect, which was not mediated by the estrogen-receptor or by protein tyrosine kinases and was not specific for breast cancer cell lines. Intracellular glutathione levels did not seem to play any role in the sensitivity of breast cancer cells to melatonin, since the addition of L-buthionine-[S,R]-sulfoximine, ethacrynic acid, or exogenous glutathione did not modify our results. We conclude that under our experimental conditions melatonin has no inhibitory effects on human breast cancer cells at low (physiological or supraphysiological) concentrations. The different experimental procedures that were utilized in the present study can partially explain the divergence between our results and the literature. 相似文献
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Oshima H Matsunaga A Fujimura T Tsukamoto T Taketo MM Oshima M 《Gastroenterology》2006,131(4):1086-1095
BACKGROUND & AIMS: Accumulating evidence indicates that prostaglandin E(2) (PGE(2)), a downstream product of cyclooxygenase 2 (COX-2), plays a key role in gastric tumorigenesis. The Wnt pathway is also suggested to play a causal role in gastric carcinogenesis. However, the molecular mechanism remains poorly understood of how the Wnt and PGE(2) pathways contribute to gastric tumorigenesis. To investigate the role of Wnt and PGE(2) in gastric cancer, we have generated transgenic mice that activate both pathways and examined their phenotypes. METHODS: We constructed K19-Wnt1 transgenic mice expressing Wnt1 in the gastric mucosa using the keratin 19 promoter. We then crossed K19-Wnt1 mice with another transgenic line, K19-C2mE, to obtain K19-Wnt1/C2mE compound transgenic mice. The K19-C2mE mice express COX-2 and microsomal prostaglandin E synthase-1 (mPGES-1) in the stomach, showing an increased gastric PGE(2) level. We examined the gastric phenotypes of both K19-Wnt1 and K19-Wnt1/C2mE mice. RESULTS: K19-Wnt1 mice had a significant suppression of epithelial differentiation and developed small preneoplastic lesions consisting of undifferentiated epithelial cells with macrophage accumulation. Importantly, additional expression of COX-2 and mPGES-1 converted the preneoplastic lesions in the K19-Wnt1 mice into dysplastic gastric tumors by 20 weeks of age. Notably, we found mucous cell metaplasia in the glandular stomach of the K19-Wnt1/C2mE mice as early as 5 weeks of age, before the dysplastic tumor development. CONCLUSIONS: Wnt signaling keeps the gastric progenitor cells undifferentiated. Simultaneous activation of both Wnt and PGE(2) pathways causes dysplastic gastric tumors through the metaplasia-carcinoma sequence. 相似文献