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21.
Radiolabeled nucleosides, specifically 5-iodo-2'-deoxyuridine (IUdR) radioiodinated with the Auger-electronemitting 123I or 125I, have been shown to produce extensive DNA damage in mammalian cell systems in vitro. Such nucleosides are cycle-dependent agents that are taken up by mitotically dividing cells in the S phase of the cell cycle. The degree of damage that occurs is related to the fact that these nucleosides bind covalently to DNA bringing the decaying Augerelectron-emitting radionuclide in close proximity to the genome. The use of these radiohalogenated nucleosides in vivo is associated with several problems. The first relates to their extremely short biologic half-life in blood (T1/2 of minutes in humans). The second involves achieving therapeutic ratios in tumor cells in the face of efficient hepatic dehalogenation. The third concerns the uptake of these radiopharmaceuticals by actively proliferating normal cell renewal systems, thus potentially causing toxic side effects. The fourth, one shared with other cycle-dependent drugs, relates to the matter of labeling the whole tumor cell population. To facilitate targeting to tumors, investigators have been examining the direct introduction of these agents into the targeted area or into an arterial blood supply that immediately precedes the target. For example, radiopharmaceutical administration could be intracavitary (bladder, spinal fluid, peritoneum), intralesional (brain tumor, breast mass) or intra-arterial (liver, pancreas). In all these situations, the following conditions must be met: (a) once within the vicinity of the tumor the agent can freely diffuse through the tissues and is selectively taken up by cancerous cells; (b) once the agent has left the target area it is converted quickly into a nontoxic form and/or excreted from the body; and finally, (c) the biologic behavior of the agent is not altered by repeated injections. We report herein our experience and that of others with [123I/125I/131I]IUdR in cultured cells, animal tumor-model systems, and patients. In vitro, DNA incorporation of 123I- and 125I-labeled IUdR leads to an exponential decrease in cell survival (no shoulder on the survival curve). However, the total number of decays needed to produce a given lethal effect with [123I]IUdR is approximately twice that required with [125I]IUdR. In vivo, the scintigraphic and antineoplastic capabilities of radioiodinated IUdR have been demonstrated in an intraperitoneal murine ovarian tumor model following intraperitoneal injection; in an intracerebral rat gliosarcoma model after intracranial administration; in an intrathecal rat gliosarcoma model after intrathecal infusion; and in a rat transitional cell bladder cancer model following intravesicular infusion. [123I]IUdR, [125I]IUdR, and/or [131I]IUdR have been administered to patients with brain, breast, colorectal, or gastrointestinal cancers (intratumorally); ovarian cancer (intraperitoneally); bladder cancer (intravesically); liver metastases from colorectal cancer (through the hepatic artery, permanent intra-arterial catheter). These studies have confirmed the observations made in animal models. The data indicate that 5-iodo-2'-deoxyuridine radiolabeled with an Auger electron emitter (123I or 125I) may be a useful agent for the scintigraphic diagnosis and/or therapy of neoplastic diseases that are accessible to direct radiopharmaceutical administration. This radiopharmaceutical should serve as a prototype for, and facilitate the development of, other radiolabeled nucleoside analogs. Further investigations are certainly warranted. 相似文献
22.
AI Robles ML Rodriguez-Puebla AB Glick C Trempus L Hansen P Sicinski RW Tennant RA Weinberg SH Yuspa CJ Conti 《Canadian Metallurgical Quarterly》1998,12(16):2469-2474
Cyclin D1 is part of a cell cycle control node consistently deregulated in most human cancers. However, studies with cyclin D1-null mice indicate that it is dispensable for normal mouse development as well as cell growth in culture. Here, we provide evidence that ras-mediated tumorigenesis depends on signaling pathways that act preferentially through cyclin D1. Cyclin D1 expression and the activity of its associated kinase are up-regulated in keratinocytes in response to oncogenic ras. Furthermore, cyclin D1 deficiency results in up to an 80% decrease in the development of squamous tumors generated through either grafting of retroviral ras-transduced keratinocytes, phorbol ester treatment of ras transgenic mice, or two-stage carcinogenesis. 相似文献
23.
泾河流域受土壤侵蚀的影响,水土流失较为严重,为对流域水土流失风险评估和防治等提供参考依据,根据1957-2017年泾河流域5个气象站点的日降水资料,运用ArcGIS空间插值、小波分析、R/S分析等方法,分析了该时段降雨量及降雨侵蚀力时空变化规律。结果表明:泾河流域及各气象站点的降雨量与降雨侵蚀力均呈显著正相关关系;泾河流域降雨量与降雨侵蚀力年内分布不均,主要集中在夏季,分别占全年的67.80%和52.86%;泾河流域年均降雨量和降雨侵蚀力分别为496.83 mm和1 481.24 (MJ·mm)/(hm~2·h),年际总体呈波动上升趋势且未来降雨侵蚀力将延续增加趋势,两者均在1996和2009年出现突变点且第一主周期分别为27和17 a;泾河流域降雨量和降雨侵蚀力在空间上均呈从西北到东南递增的趋势。 相似文献
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介绍了如何提高甲醇触媒的活性及寿命,进一步降低电耗。文中对“精脱硫新工艺”的研发及设备的选取作了详细的论述。 相似文献
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介绍了啤酒废水的特点,阐述了UASB—SBR工艺处理啤酒废水的工艺流程。经工程实际运行表明,可稳定达到国家二级排放标准,同时获得了显著的经济效益。 相似文献
29.
基于FPGA的光栅尺位置速度反馈模块设计 总被引:1,自引:0,他引:1
利用FPGA的高速运算能力,建立一个数据采集处理模块,该模块的任务是采集光栅尺输入信号,对采集到的信号进行分析处理,得出速度、位移、方向等物理量.并对该模块进行了仿真,结果表明模块可以很好地完成预定任务. 相似文献
30.
以广西某高校170名医学高职生为研究对象,通过问卷、访谈和B级成绩调查高职生英语学习策略的运用特点,结果表明高职生较多运用组织性计划、联想和自我交谈策略,较少运用听觉再现策略;女生比男生更多地运用自我交谈策略来降低学习的焦虑;高分组比低分组更熟练地运用推断策略;学生B级成绩的21.2%直接受到联想策略运用水平的影响.对造成这些差异的原因进行了分析,并指出在教学中要加强对学生的学习策略的培训. 相似文献