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21.
hTERT启动子调控hNIS基因介导肺癌细胞碘摄取和131I治疗的实验研究 总被引:1,自引:1,他引:0
目的 构建含人端粒酶反转录酶(hTERT)核心启动子调控的人钠/碘同向转运体(hNIS)基因重组腺病毒,并靶向转染至肺癌A549细胞中特异性表达.探讨hTERT启动子调控的hNIS基因介导放射性碘治疗肿瘤的可能性.方法 应用AdEasy系统构建重组腺病毒Ad-hTERT-hNIS,同时构建巨细胞病毒(CMV)启动子调控的hNIS重组腺病毒Ad-CMV.hNIS作为阳性对照,不含hNIS的重组腺病毒Ad-CMV作为阴性对照.应用反转录.聚合酶链反应(RT-PCR)方法验证hTERT在转染肿瘤细胞中的转录活性,摄碘实验检测表达的hNIS蛋白功能,细胞克隆形成实验评价131I对转染肿瘤细胞的毒性作用.结果 成功构建重组腺病毒Ad-hTERT-hNIS、Ad-CMV-hNIS及Ad-CMV,并经PCR验证正确.RT-PCR证实hNIS cDNA能从Ad-hTERT-hNIS转染的细胞中扩增出来.Ad-hTERT-hNIS和Ad-CMV-hNIS转染的肺癌A549细胞摄碘能力比阴性对照组Ad-CMV转染的细胞分别提高了23和31倍,且摄碘能力可以被NaClO4抑制.Ad-hTERT-hNIS和Ad-CMV-hNIS转染的肺癌A549细胞均可被131I杀死,2组细胞成活率分别为(31.2±1.45)%和(23.6±4.08)%,而阴性对照组和未转染病毒组分别为(89.0 ±2.99)%和(91.2 ±4.63)%.结论 hTERT启动子调控的hNIS重组腺病毒转染肿瘤细胞后,应用131I治疗有望成为一种新的基因靶向治疗手段. 相似文献
22.
Despite the use of gold complexes in modern medicine for over 100 years and the use of gold complexes in the management of
rheumatoid disease for more than 60 years, the definitive mechanisms of action for efficacy and for toxicity have not been
established.
Gold is a group 1b metal in the periodic table with several oxidation states but it is only Au(I) which is active in the biological
milieu. Gold sodium thiomalate is not only a polymeric structure, but also has the chiral ligand, thiomalic acid. Gold sodium
thiomalate thus can exist in several different physical states which may have different biological activity. In addition the
pharmacokinetic profile of gold complexes has been of little value in the understanding of either the mechanism of action,
efficacy or toxicity for both the injectable and the oral gold complexes. Many authors have misinterpreted research data on
the activities of gold complexes because they compared gold complexes of different structures, and gold complexes which exist
at different pH.
Experimental work in our laboratory has identified that gold sodium thiomalate is a mixture and can exist as either a yellow
or a colourless solution. These have some similar but several different biological activities.
Many factors contribute to the lack of understanding of the action of gold complexes. Some of these factors are related to
the wide variation in physical structure and biological activities exhibited by these compounds. 相似文献
23.
4-甲氧基-2-巯基-N-氧化吡啶钠的抗肿瘤及免疫抑制作用 总被引:1,自引:0,他引:1
4-个甲氧基-2-巯基-N-氧化吡啶钠(4-甲氧基巯氧吡啶钠,SodiumMethoxypyridinethione,SMPT)在试管内0.01mg·L-1可抑制多种传代人癌细胞林,抑制细胞有丝分裂和损害细胞膜相结构,单用对动物移植性肿瘤无效,但明显增强氟脲嘧啶对小鼠S180的抑癌作用。使胸腺和脾脏重量明显减轻,抑制SRBC诱导的小鼠血清溶血素反应,抑制DNCB诱导的豚鼠皮肤迟发型超敏反应,抑制PHA诱导的大鼠3H-TdR参入的淋巴细胞转化。与2-巯基-N-氧化吡啶钠(巯氧吡啶钠,SodiumPyridinethione.SPT)比较,小鼠LD50(ip)增大,而试管内抑瘤的IC50相近。 相似文献
24.
Shelley A. Klemm Richard D. Gordon Terry J. Tunny Wendy L. Finn 《Clinical and experimental pharmacology & physiology》1990,17(3):191-195
1. Plasma potassium and chloride concentrations were raised and plasma renin activity, aldosterone, bicarbonate and arterial pH were reduced in two brothers with the syndrome of hypertension and hyperkalaemia with normal glomerular filtration rate (Gordon's syndrome), on unrestricted or moderately restricted sodium diets. 2. These abnormalities were corrected in both patients within 10 days of severe sodium restriction. 3. Pressor sensitivity to cold and angiotensin II decreased on low sodium diet, associated with a fall in blood pressure. 4. Increasing distal tubular sodium delivery by infusion of normal saline increased fractional excretion of potassium when aldosterone had been stimulated by severely restricted sodium diet, but not when aldosterone levels were low on unrestricted sodium diet. 5. These findings are consistent with excessive sodium reabsorption as the primary renal lesion in Gordon's syndrome, leading to volume expansion and suppression of renin and aldosterone. Severe dietary sodium restriction leading to volume contraction, by stimulating renin and aldosterone and promoting kaliuresis, corrects the abnormalities. 相似文献
25.
本实验用C_(57)BL/6j小鼠CFU-GM集落形成的方法观察了三种CSF和氢化可的松、锂盐及硒盐对CFU-GM的影响及其对IFN的CFU-GM抑制作用的阻断作用。结果表明,三种CSF能部分拮抗IFN的CFU-GM抑制效应;微量的硒酸钠,碳酸锂均可刺激CFU-GM增殖,并使IFN200IU抑制的CFU-GM产率提高200%以上;微量的氢化可的松也能部分阻断IFN的CFU-GM抑制。 相似文献
26.
应用标准微电极技术,研究了关附甲素对豚鼠右心室乳头肌动作电位最大除极速率(Vmax)的频率依赖性抑制作用(RDB),并与美西律,奎尼丁,劳卡尼进行了比较. 在相同刺激间隔(300 ms),产生50%左右RDB的药物浓度下,美西律的RDB开始最快,其第2个Vmax所产生的抑制已占RDB的64%,奎尼丁,劳卡尼和关附甲素的RDB开始速率常数分别为每个动作电位0.165, 0.076和0.136. 美西律,奎尼丁,劳卡尼和关附甲素产生RDB的恢复时间常数分别为1.4, 9.0, 18.2和44.0 s,而且它们的恢复时间常数是不依赖于药物浓度而变化的,结果提示,关附甲素是一个慢动力学钠通道阻滞剂. 相似文献
27.
采用高效液相色谱法测定双氯芬酸钠滴眼液的含量,方法简便,准确,能将药与杂质峰完全分离。应用化学动力学原理以恒温加试验预测双氯芬酸钠滴眼液稳定性及有效期,室温下有效期t^25℃0.9约为2.57年,与留样观察结果相符。 相似文献
28.
29.
Ingrid Gouldsborough Nick Ashton 《Clinical and experimental pharmacology & physiology》1998,25(12):1024-1031
1. The aim of the present study was to compare electrolyte handling in naturally reared neonatal spontaneously hypertensive rats (SHR) with those reared by a Wistar-Kyoto (WKY) rat foster mother (denoted SHRX), as cross-fostering SHR pups to a WKY rat dam lowers adult blood pressure in the SHR. 2. The electrolyte content of WKY rat and SHR dams’ milk was determined and electrolyte intake and urinary excretion rates were calculated in both naturally reared and cross-fostered WKY rat and SHR pups. 3. The milk sodium concentration fell in both strains (WKY rat: 31.8 ± 2.0 to 15.2 ± 1.2 mmol/L; SHR 31.9 ± 2.5 to 18.2 ± 1.6 mmol/L; P < 0.001), as did potassium (P < 0.001), over lactation, but there were no differences between strains. Calcium and magnesium concentrations increased (P< 0.001), although SHR dam's milk contained less calcium (P < 0.001) than that of WKY rat dams during the third week of lactation. 4. Spontaneously hypertensive rat pups ingested less milk (P<0.05) than WKY rat pups; therefore, their cumulative sodium intake over postnatal days 4–15 was significantly lower than that of WKY rat pups (WKY rat vs SHR: 84.4 ± 3.6 vs 59.7 ± 2.6 μmol/g bodyweight, respectively; P < 0.05) and fostered SHRX pups (77.7 ± 7.0 μmol/g bodyweight; P < 0.05). Potassium and magnesium intakes were comparable between SHR, WKY rat and SHRX pups, but SHR pups ingested significantly less calcium than either WKY rat pups (136.1 ± 6.4 vs 200.1 ± 9.5p, mol/g bodyweight, respectively; P<0.05) or SHRX pups (200.0 ± 18.0 μmol/g bodyweight; P<0.05). 5. These data show that the neonatal SHR experiences a period of sodium deficiency during the developmental stage when cross-fostering is effective in lowering blood pressure. This is consistent with the reported up-regulation of the renin-angiotensin system observed in SHR at this time and may have a long-term influence on blood pressure. 相似文献
30.
Satomi Kitagawa Yu Yamaguchi Emiko Sameshima Masaru Kunitomo 《Clinical and experimental pharmacology & physiology》1994,21(12):963-970
1. Endothelium-dependent relaxation in response to acetylcholine (ACh) and the calcium ionophore A 23187 was examined in aorta, coronary, basilar and renal arteries isolated from Watanabe heritable hyperlipidaemic (WHHL) rabbits of 2, 6 and 12 months of age, with normolipidaemic heterozygous WHHL rabbits as controls. 2. In the rings of WHHL rabbit aortae and coronary arteries preconstricted with vasoconstrictors, endothelium-dependent relaxation in response to ACh was attenuated with age compared to the heterozygous WHHL rabbits. A significant negative correlation was found between the total cholesterol content and the relaxation response to ACh in the aortae or coronary arteries from 6 and 12 month old WHHL rabbits. 3. In the rings of basilar arteries, endothelium-dependent relaxations to ACh were not modified with age. Similarly, in the rings of renal arteries, the relaxation response to ACh was not changed with age, but in the 6 and 12 month preparations, after the age of 6 months, a contraction following the relaxation appeared at higher concentrations of ACh (10?7 to 10?6 mol/L). The contraction was endothelium-dependent and inhibited by indomethacin. 4. A 23187-induced endothelium-dependent relaxations were also markedly attenuated in the aorta and significantly in the coronary artery with age. 5. Endothelium-independent relaxation to sodium nitroprusside was not changed in all arteries from WHHL rabbits of different ages. 6. These findings indicate that in the aorta and coronary artery of the WHHL rabbit, the endothelium-dependent relaxation to ACh and A 23187 becomes impaired with increasing age (i.e., with the progression of cholesterol deposition in the arterial wall) but is preserved in the basilar and renal artery. 相似文献