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1.
《肿瘤代谢与营养电子杂志》2018,5(2):144-150
目的 研究 MTX 对 RAS 蛋白定位改变以及下游信号途径的影响,并探讨 MTX 抑制人胶质母细胞瘤细胞株 U87 生长的可能机制。方法 不同浓度的MTX(75nmol/L、375nmol/L、750nmol/L、7,500nmol/L、15,000nmol/L)处理 U87细胞后, 采用MTT 法和FCM 法分别检测细胞活力,细胞凋亡率及细胞周期。RAS-GFP 和蛋白质印迹法分别检测RAS 蛋白的分布 定位和其下游MAPK/ERK 蛋白的表达水平。采用逆转录病毒法将RAS-GFP 融合基因转导至U87 细胞,共聚焦显微镜技 术能检测到RAS 活化后定位分布,与不同的MAKP/ERK 信号途径特异性抑制剂(U0126 和 PD98059)共培养,采用蛋白 质印迹法检测MTX 对 P-P42/P44 MARK 蛋白磷酸化水平的影响以及其调控转录因子c-MYC 表达水平发的影响。50nmol/L 的 MTX 处理 U87 细胞后,进一步用 FCM 法检测细胞表面分子 CD47 的表达水平。结果 不同浓度的 MTX(75nmol/L、 375nmol/L、750nmol/L、7,500nmol/L、15,000nmol/L)均能抑制人神经胶质母细胞瘤细胞株 U87 的增殖,呈剂量依赖性, 不同浓度的MTX 可将U87 细胞阻滞于个G2/S 期,并不能直接诱导细胞发生凋亡。转导RAS-GFP 融合基因到U87 细胞 (100% GFP),同对照组相比,用MTX 处理后发现RAS 蛋白从细胞膜转移到细胞质,从而通过降低或者抑制P-p42/p44 MARK 蛋白磷酸化水平(P < 0.05),以及抑制转录因子 c-MYC 的表达水平(P < 0.05),导致 U87 细胞生长受到抑制。 我们还近一步证明了 MTX 抑制与神经胶质母细胞瘤生长密切相关的细胞表面分子 CD47 在不同时间的表达水平。结论 我 们首次证明MTX通过改变RAS蛋白定位抑制MAPK/ERK/C-MYC信号导致神经胶质母细胞瘤U87细胞株的生长收到抑制, 细胞停滞在 G2/S 期,提示 MTX 有可能作为复发胶质瘤患者可选的治疗药物。 相似文献
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细胞因子与OPG/RANK/RANKL系统 总被引:1,自引:1,他引:1
骨骼不断地进行新陈代谢,骨形成与骨吸收贯穿于骨代谢的全过程,二的平衡维持着骨量稳定。成骨细胞与破骨细胞是骨形成与吸收的执行体,受循环激素及细胞因子的凋控。而骨保护素(osteoprotegerin)、核因素子.KB受体活化因子(receptor activator of nuclear factor-[Kappa]B)、核因子-KB受体活化因子配体(receptor activator of nuclear factor-[Kappa]B ligand)系统即OPG/RANK/RANKL系统, 相似文献
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目的:分析T1micN0M0、T1aN0M0和T1bN0M0乳腺癌患者的临床病理学特征,了解其生存状态,探讨与预后相关的独立影响因素。方法:收集2002年1月—2005年12月4487例可手术的乳腺癌患者的临床病理学资料,回顾性分析其中376例T1micN0M0、T1aN0M0和T1bN0M0患者的临床病理学特征、复发和转移以及生存情况。结果:376例患者中,66例(17.6%)为T1mic(pT≤0.1cm),122例(32.4%)为T1a(0.1cm相似文献
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Background
Data on Human Papilloma virus (HPV) vaccine immune response in sub-Saharan Africa is still sparse yet such knowledge is critical for optimal implementation and monitoring of HPV vaccines. Our primary objective was to evaluate levels of anti-HPV-16/18 antibodies and six other ‘high risk’ HPV (hrHPV) types among the vaccinated and unvaccinated Ugandan girls.Methods
We conducted a cross sectional study among AS04-adjuvanted HPV-16/18 vaccinated and unvaccinated school girls aged 10–16 years in Western Uganda using purposive sampling. The vaccinated girls were at 18 months post vaccination. After consenting and assenting, data was collected using interviewer administered questionnaires for demographics and sexual history. Blood was drawn from which serum samples were analysed by the multiplex HPV serology technology to determine anti-HPV antibody levels to HPV-16/18 and six other hrHPV types (31, 33, 35, 45, 52 and 58). The antibody levels were expressed as Median Fluorescent Intensity (MFI).A total of 207 vaccinated [mean age 13.1 years (SD 1.5); range 10-16 years] and 197 unvaccinated girls [mean age 13.6 years (SD 1.3); range 10-16 years] participated in the study. Sexual activity was self reported among 14/207 (6.8%) vaccinated and 5/197 (2.5%) unvaccinated girls. The MFI levels for HPV-16 and HPV-18 were 15 and 20 times higher respectively in the vaccinated girls than in the unvaccinated girls. HPV-16 mean MFI level was 4691(SD 1812; 95% CI: 4438-4958) among the vaccinated compared to 218 (SD 685; 95% CI: 190-252) among the unvaccinated girls. For HPV-18 the mean MFI level was 1615 (SD 1326; 95% CI: 1470-1776) among the vaccinated compared to MFI 103 (SD 506; 95% CI: 88 -121) among unvaccinated girls.In addition antibody levels to non vaccine hrHPV types (31, 33, 35, 45, 52 and 58) were all significantly higher in the vaccinated group than in the unvaccinated group (p<0.01).Conclusion
The AS04-Adjuvanted HPV-16/18 vaccinated girls showed a higher level of antibodies to HPV-16/18 and other non-vaccine hrHPV types compared to the unvaccinated girls. This may translate into protection against HPV-16/18 and other hrHPV types.5.
胃粘膜上皮分泌的粘液系一类糖蛋白,其中包括中性和酸性粘液,后者又分为硫酸和诞酸粘液,自Spicer等报道AB(pH2.5)—PAS方法以来,多采用该染色方法对中性和酸性粘液物质加以鉴别,并已广泛应用于肠化类型研究和病理诊断。以后又发明了高铁双胺(HID)—AB(pH2.5)法,可鉴别硫酸和诞酸粘液,tess等指出硫酸粘液 相似文献
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目的探讨多孔聚丙烯晴基碳纤维/壳聚糖/双相磷酸钙/聚乳酸-羟基乙酸(PAN/CS/BCP/PLGA)复合支架作为骨组织工程支架材料的可行性。方法采用湿法合成双相磷酸钙,真空冷冻干燥技术制备多孔PAN/CS/BCP/PLGA复合支架,测定抗压强度、阿基米德法测定孔隙率及体外模拟生物活性,并采用XRD、SEM分析相结构及形貌特征。结果 PAN/CS/BCP/PLGA复合支架中添加4wt%PAN后,平均孔隙率大于85%,抗压强度大于5.9 MPa,提高了6倍,生物可降解速率低于9.5%,呈现多孔贯通形貌,孔径平均为400~500μm,PAN分布均匀,体外模拟实验表明支架表面生成类骨磷灰石。结论多孔PAN/CS/BCP/PLGA复合支架具备良好的生物活性和生物可降解性,为其成为骨组织工程支架材料提供理论依据。 相似文献
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Marina Inés Flamini Ivonne Denise Uzair Gisela Erika Pennacchio Flavia Judith Neira Joselina Magali Mondaca Fernando Dario Cuello-Carrión Graciela Alma Jahn Tommaso Simoncini Angel Matías Sanchez 《Hormones & cancer》2017,8(1):16-27
Thyroid hormones (TH) play a fundamental role in diverse processes, including cellular movement. Cell migration requires the integration of events that induce changes in cell structure towards the direction of migration. These actions are driven by actin remodeling and stabilized by the development of adhesion sites to extracellular matrix via transmembrane receptors linked to the actin cytoskeleton. Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that promotes cell migration and invasion through the control of focal adhesion turnover. In this work, we demonstrate that the thyroid hormone triiodothyronine (T3) regulates actin remodeling and cell movement in breast cancer T-47D cells through the recruitment of FAK. T3 controls FAK phosphorylation and translocation at sites where focal adhesion complexes are assembled. This process is triggered via rapid signaling to integrin αV/β3, Src, phosphatidylinositol 3-OH kinase (PI3K), and FAK. In addition, we established a cellular model with different concentration of T3 levels: normal, absence, and excess in T-47D breast cancer cells. We found that the expression of Src, FAK, and PI3K remained at normal levels in the excess of T3 model, while it was significantly reduced in the absence model. In conclusion, these results suggest a novel role for T3 as an important modulator of cell migration, providing a starting point for the development of new therapeutic strategies for breast cancer treatment. 相似文献
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暴露于环境危险因素对人群健康的影响广泛,检测有效的生物标志物有助于评估人群暴露的健康风险。近年来,PIG-A基因突变测定被尝试用于评估人群暴露于环境因素的致突变效应。本文综述了健康人群中PIG-A基因突变测定方法、突变水平、影响因素以及应用现状的研究进展,发现目前PIG-A基因突变测定方法技术可行,但检测结果的个体间变异较大,多项研究发现PIG-A基因突变率与年龄、性别等因素的关联并不一致,更多潜在的影响因素仍在探索中。今后有必要进行更大样本量的人群研究,获得人群的基线水平,明确机体因素和环境因素对个体间变异的作用。在应用时需结合同期健康对照和暴露前后的数据进行综合分析,促进该方法应用于人体真实暴露后的健康风险评估。 相似文献
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胸部肿瘤放疗过程中正常肺组织不可避免受到照射,发生放射性肺损伤,主要病理表现为受照区域炎性细胞聚集、细胞因子释放、成纤维细胞聚集和增殖以及肺泡间隔胶原过度沉积。放射性肺损伤严重影响胸部放疗患者治疗顺应性和生存质量,甚至威胁其生命。近年来,大量研究发现Th1、Th2免疫失衡与放射性肺损伤的发生发展关系密切,相关细胞因子网络在放射性肺损伤进展过程中发挥执行作用,因此恢复体内Th1、Th2免疫平衡可能为防治放射性肺损伤提供新途径。 相似文献
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神经母细胞瘤是第二常见的儿童颅外实体肿瘤,一般发现时70%已出现侵袭/转移,而骨侵袭/转移是其致残致死的关键原因.在这一过程中神经母细胞瘤细胞、成骨细胞及其前体细胞、破骨细胞及其前体细胞和骨髓基质细胞通过一系列相关因子促进骨侵袭/转移发生,其中RANK/RANKL/OPG通路在骨侵袭/转移过程中的作用至关重要.本文通过RANK/RANKL/OPG信号转导通路对神经母细胞瘤骨侵袭/转移机制的研究进展做一综述. 相似文献
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Purpose
Low α/β ratio for breast cancer has drawn a growing interest for exploring hypofractionation for breast irradiation. This work is to confirm the low α/β ratio based on large randomized clinical trials of breast irradiation.Methods and materials
A model based on the generalized linear-quadratic (LQ) model and Poisson statistical model was developed to calculate disease-free survival with consideration of clonogen proliferation during the course of radiation treatment and exponential behavior of survival rate with follow-up time. Outcome data from a series of randomized clinical trials of early-stage breast radiotherapy were fitted to estimate the model parameters. Other clinical outcomes, including treatments with surgery alone or radiotherapy alone were used to validate the model and the estimated parameters. Hypofractionation regimens were proposed based on the newly estimated LQ parameters.Results
Plausible population averaged radiobiologic parameters for breast cancer (95% confidence level) are α/β = 2.88 (0.75–5.01) Gy; α = 0.08 ± 0.02 Gy−1; potential doubling time Td = 14.4 ± 7.8 day. The analysis of the radiation-alone data suggested an α/β ratio of 3.89 ± 6.25 Gy, verifying the low α/β ratio based on the post-lumpectomy irradiation data. The hypofractionation regimens that are equivalent to the conventional regimen of 2.0 Gy × 25 in 5 weeks include 2.26 Gy × 20, 3.34 Gy × 10, 4.93 Gy × 5 or 3.39 Gy × 10 (BID).Conclusions
The analysis of the available clinical data from multiple institutions support that breast cancer has a low ratio of α/β, encouraging hypofractionated radiotherapy regimens for breast cancer. 相似文献16.
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目的 比较内镜黏膜下剥离术(ESD)联合放疗与食管鳞癌根治术在Tis/T1N0M0期食管鳞癌患者中的疗效和安全性。方法 回顾性选取2015-08-01-2019-10-31在东南大学附属中大医院行ESD联合放疗(ESD+放疗组,n=48)与行食管鳞癌根治术(手术组,n=36)的Tis/T1N0M0期食管鳞癌患者,采用t检验、χ2检验或Fisher’s精确检验比较2组患者基本特征和不良反应,采用Kaplan-Meier法及Cox回归模型进行生存分析,观察ESD联合放疗与食管鳞癌根治术相比的安全性及有效性。同时评估ESD联合放疗对于老年患者的安全性。结果 2组中位生存期均未达到,ESD+放疗组平均无进展生存期为82个月,手术组为88个月。ESD+放疗组平均总生存期为80个月,手术组为86个月。ESD+放疗组的3年无进展生存率和总生存率分别为95.7%和93.7%,手术组分别为91.1%和91.2... 相似文献
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由ESTRO/ESMO/EHNS与中华医学会放射肿瘤治疗学分会主办,中国医学科学院肿瘤医院承办的“头颈部肿瘤综合治疗(MULTIDISCIPLINARY MANAGEMENT OF HEAD & NECK CANCER)”培训课程将于2015年6月14—17日在北京举办。一、培训内容:头颈部肿瘤综合治疗课程将由欧洲ESTRO/ESMO/EHNS三大学会联合举办,聘请头颈部肿瘤各个专业的专家授课,将围绕头颈部肿瘤的影像诊断、手术治疗、放射治疗、化疗、靶向治疗等方面进行有针对性培训,旨在指导正确合理地治疗头颈部肿瘤。二、培训对象:该培训课程主要针对从事头颈部肿瘤诊断、治疗的外科医生、放疗科医生、肿瘤内科医生、影像科医生,以及参与到头颈部肿瘤诊疗工作的其他人员。会议配有中英文双语幻灯和现场翻译。参会学员将获得国家级继续教育学分。三、会议日程:报到:2015年6月13日(星期六)12:00AM-8:00PM(京瑞大厦前台)日程:2015年6月14日(星期日)9:00AM-2015年6月17日(星期三)6:00PM四、会议地点:京瑞大厦:北京市朝阳区东三环南路17号(距离肿瘤医院三公里左右)。电话:010-67668866;网址:http://www.kingwing.com.cn五、注册方式:会议采用网上注册方式(请登录中华医学会网站)。网上注册费用为1500元。费用包含学费、场租费、专家授课及交通费,以及会议期间午、晚餐、茶歇费用。学员交通费、住宿费等自理(京瑞大厦标间费用为450元/间夜)。详细信息请关注微信公众号“放疗微达人”。为保证培训班的授课质量,沿用限制参会人数的方式,本班限定300人,以完成注册为准。不周之处,敬请谅解!六、会务联系:联系人:田凤华,Email: fhtian@hotmail.com;Tel:010-87788280;传真:67706153;张涛,Email:zhangt10@126.com。负责人:金晶,Email: jingjin1025@163.com。 相似文献
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Shujun Liu Lai-Chu Wu Jiuxia Pang Ramasamy Santhanam Sebastian Schwind Yue-Zhong Wu Christopher J. Hickey Jianhua Yu Heiko Becker Kati Maharry Michael D. Radmacher Chenglong Li Susan P. Whitman Anjali Mishra Nicole Stauffer Anna M. Eiring Roger Briesewitz Robert A. Baiocchi Kenneth K. Chan Peter Paschka Guido Marcucci 《Cancer cell》2010,17(4):333-347