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1.
靶向Survivin的siRNA联合吉西他滨抑制胰腺癌细胞增殖   总被引:1,自引:0,他引:1  
目的 构建靶向Survivin基因的siRNA真核表达载体,观察其对吉西他滨化疗抑制胰腺癌Pane-1细胞增殖的影响.方法 构建靶向Survivin基因的siRNA真核表达载体psiRNA-Survivin,行酶切和测序鉴定.用重组质粒转染Pane-1细胞并筛选稳定转染的细胞株,绘制细胞生长曲线.采用逆转录.聚合酶链反应(RT-PCR)、Western blot检测Survivin的mRNA和蛋白表达变化.以吉西他滨分别作用于对照组和转染组Panc-1细胞24 h,噻唑蓝(MTY)比色法检测细胞的增殖,流式细胞仪检测细胞的凋亡.结果 酶切和测序鉴定表明,成功构建了psiRNA-Survivin重组质粒.重组质粒稳定转染胰腺癌细胞株后,Survivin的mRNA和蛋白表达分别下调了79.2%和83.6%(P<0.05),生长曲线明显变平缓,并能显著增强吉西他滨对Panc-1细胞的增殖抑制[(24.6±4.5)%/(38.7±5.2)%]和凋亡诱导作用[(16.7±2.5)%/(26.8±3.4)%,P<0.05).结论 构建Survivin的siRNA表达载体可明显下调Survivin的表达,抑制Panc-1细胞增殖,并能提高细胞对吉西他滨的化疗敏感性.  相似文献   

2.
目的 运用基因转染技术,观察DPC4基因转染对胰腺癌细胞化疗敏感性的影响.方法 构建表达DPC4基因的逆转录病毒载体,转染胰腺癌细胞BxPC-3,获取稳定表达DPC4的子代胰腺癌的细胞株BxPC-3/DPC4.观察5-Fu、吉西他滨(作用72 h)对胰腺癌细胞的抑制作用.同时应用半定量RT-PCR检测胰腺癌细胞内Mdr-1、Chk1基因的表达情况.结果 DPC4基因转染并稳定表达后,BxPC-3细胞对5-Fu、吉西他滨的IC50浓度(72 h)分别降低了1倍左右.同一浓度下,5-Fu、吉西他滨联合DPC4基因转染对BxPC-3细胞的体外抑制作用也明显增强,癌细胞内的Mdr-1、Chk1基因的mRNA表达明显下调.显示单独使用pLXSN/DPC4、5-Fu、吉西他滨,均能在体外抑制胰腺癌细胞的生长,但pLXSN/DPC4联合化疗药物,对癌细胞生长的抑制作用更为明显.结论 DPC4基因转染能够提高胰腺癌细胞对化疗药物的敏感性,其机制可能是通过下调Mdr-1、Chkl的表达来实现的.  相似文献   

3.
目的 运用基因转染技术,观察DPC4基因转染对胰腺癌细胞化疗敏感性的影响.方法 构建表达DPC4基因的逆转录病毒载体,转染胰腺癌细胞BxPC-3,获取稳定表达DPC4的子代胰腺癌的细胞株BxPC-3/DPC4.观察5-Fu、吉西他滨(作用72 h)对胰腺癌细胞的抑制作用.同时应用半定量RT-PCR检测胰腺癌细胞内Mdr-1、Chk1基因的表达情况.结果 DPC4基因转染并稳定表达后,BxPC-3细胞对5-Fu、吉西他滨的IC50浓度(72 h)分别降低了1倍左右.同一浓度下,5-Fu、吉西他滨联合DPC4基因转染对BxPC-3细胞的体外抑制作用也明显增强,癌细胞内的Mdr-1、Chk1基因的mRNA表达明显下调.显示单独使用pLXSN/DPC4、5-Fu、吉西他滨,均能在体外抑制胰腺癌细胞的生长,但pLXSN/DPC4联合化疗药物,对癌细胞生长的抑制作用更为明显.结论 DPC4基因转染能够提高胰腺癌细胞对化疗药物的敏感性,其机制可能是通过下调Mdr-1、Chkl的表达来实现的.  相似文献   

4.
目的 运用基因转染技术,观察DPC4基因转染对胰腺癌细胞化疗敏感性的影响.方法 构建表达DPC4基因的逆转录病毒载体,转染胰腺癌细胞BxPC-3,获取稳定表达DPC4的子代胰腺癌的细胞株BxPC-3/DPC4.观察5-Fu、吉西他滨(作用72 h)对胰腺癌细胞的抑制作用.同时应用半定量RT-PCR检测胰腺癌细胞内Mdr-1、Chk1基因的表达情况.结果 DPC4基因转染并稳定表达后,BxPC-3细胞对5-Fu、吉西他滨的IC50浓度(72 h)分别降低了1倍左右.同一浓度下,5-Fu、吉西他滨联合DPC4基因转染对BxPC-3细胞的体外抑制作用也明显增强,癌细胞内的Mdr-1、Chk1基因的mRNA表达明显下调.显示单独使用pLXSN/DPC4、5-Fu、吉西他滨,均能在体外抑制胰腺癌细胞的生长,但pLXSN/DPC4联合化疗药物,对癌细胞生长的抑制作用更为明显.结论 DPC4基因转染能够提高胰腺癌细胞对化疗药物的敏感性,其机制可能是通过下调Mdr-1、Chkl的表达来实现的.  相似文献   

5.
Survivin反义寡核苷酸诱导肝癌细胞凋亡及细胞结构的变化   总被引:5,自引:0,他引:5  
目的采用反义寡核苷酸封闭肝癌细胞中Survivin基因的表达,研究其诱导细胞凋亡过程中对细胞超微结构与细胞骨架的作用及其机理。方法采用脂质体介导Survivin反义寡核苷酸转染人肝癌细胞株SMMC-7721细胞,Western—blot及原位杂交方法检测Survivin蛋白及mRNA表达,流式细胞仪检测细胞凋亡比率,透射电子显微镜观察细胞超微结构变化,激光共聚焦显微镜观察细胞骨架微丝系统变化,激酶活性检测方法测定细胞内Caspase-3活性变化。结果脂质体介导Survivin反义寡核苷酸转染肝癌细胞后Survivin蛋白及mRNA表达分别由69.59及75.60降低至10.71及22.90,Caspase-3活性由0.0153升高至0.0992,同时细胞结构呈典型凋亡改变,细胞内微丝形态结构破坏,细胞凋亡比率由0.7%增加至31.4%。结论脂质体介导转染Survivin反义寡核苷酸可以有效降低细胞内Survivin基因的表达,并激活Caspase-3。活化的Caspase-3可以切割破坏细胞内骨架微丝系统的结构,进而诱导细胞凋亡。  相似文献   

6.
目的: 观察反义缺氧诱导因子-1α(HIF-1α)对胰腺癌细胞BxPC-3化疗敏感性的影响。方法:实验分组:(1)缺氧条件下(0.5% O2)体外培养4h,未转染反义HIF-1α质粒的BxPC-3细胞设为缺氧对照组;(2)常氧条件下体外培养,未转染反义HIF-1α质粒的BxPC-3 细胞设为常氧对照组;(3)缺氧条件下(0.5% O2)体外培养4h,稳定转染反义HIF-1α质粒的BxPC-3细胞设为实验组。采用逆转录聚合酶链反应 (RT-PCR)和免疫印迹(Western Blot)检测各组的HIF-1α和survivin表达情况。 流式细胞术和MTT比色法检测不同剂量的化疗药物(5-氟尿嘧啶、阿霉素、吉西他宾)对各组的凋亡率和生长抑制率的影响。 结果:实验组HIF-1α和survivin的表达明显降低 (P<0.05),与对照组相比,实验组的凋亡率、抑制率与剂量成正比,高剂量引起高抑制(P<0.05)。 结论:反义HIF-1α可能通过阻断survivin的表达而增强胰腺癌对化疗的敏感性。据此可望通过阻断HIF-1α的表达为胰腺癌基因治疗提供一种新途径。  相似文献   

7.
目的研究生存素(Survivin)反义寡核苷酸(ASODN)对胃癌细胞系HS746T的抑制作用。方法应用SurvivinASODN转染胃癌细胞,设空白、脂质体和正义链对照组,100、200和400nmol/L反义链组。电镜下观察细胞超微结构,流质细胞术、四甲基偶氮唑盐(MTT)法、逆转录聚合酶链反应(RTPCR)及Westernblot法检测转染后2~48h细胞凋亡指数(AI),生长抑制率(IR),SurvivinmRNA和蛋白表达的变化。结果转染后反义链组均能够下调SurvivinmRNA含量和蛋白表达,凋亡细胞增多。转染后24h100、200和400nmol/L反义链组AI为14.8%、19.4%及53.8%;IR(%)为45.98±2.99、50.96±3.38、72.79±2.48,反义链组高于其他对照组。结论Survivin反义寡核苷酸能够抑制胃癌细胞增殖。  相似文献   

8.
目的 观察RNA干扰(RNAi)抑制膀胱癌T24细胞中血管内皮生长因子C(VEGF-C)表达和提高化疗敏感性.方法 根据转染效率最高时pEGFPN1质粒与脂质体的比例,转染T24细胞,实验分为3组,逆转录-聚合酶链反应(RT-PCR)检测VEGF-C mRNA的表达,流式细胞仪分析细胞凋亡率.结果 转染后24 h,即有mRNA表达水平的下降,Quantity one半定量:24 h 0.57±0.17,48 h 0.42±0.11,72 h0.33±0.09.VEGF-C抑制后,吉西他滨诱导的凋亡率明显升高,转染组为(41.38±1.54)%,明显高于未转染组(22.87±1.40)%与脂质体组(23.47±1.58)%(P<0.05).结论 RNAi可高效稳定抑制膀胱癌T24细胞中VEGF-C的表达,明显提高吉西他滨诱导膀胱癌T24细胞凋亡的药物敏感性.  相似文献   

9.
[目的]研究人骨肉瘤细胞MG63中反义RNA对Survivin表达的抑制作用。[方法]培养骨肉瘤细胞MG63,采用RT—PCR的方法克隆人Survivin基因编码区cDNA。构建Survivin的反义诱导表达载体。转染MG63细胞,G418筛选稳定转染的细胞系。稳定转染的细胞系,以ZnSO4 120μmol/L诱导,HE染色、Survivin免疫细胞化学染色透射电镜等形态学观察。绘制生长曲线。RT—PCR检测各组细胞Survivin的表达。Annexin V法检测细胞凋亡。[结果]RT—PCR从MG63细胞mRNA扩增了Survivin编码区cDNA,约420bp。构建了pMDNA3-anti—Survivin重组质粒。转染MG63细胞,G4181000μg/ml筛选4周后,建成稳定转染细胞系。通过ZnSO4 120μmol/L诱导,电子显微镜观察可见MG63/pMDNA3-anti—Survivin细胞出现凋亡。免疫细胞化学染色可见诱导后的MG63/pMDNA3-anti—Survivin Survivin蛋白表达明显降低。AnnexinV染色后发现pMDNA3-anti—Survivin细胞,在ZnSO4诱导48h后凋亡率达到11%,较对照组高出3倍。[结论]Survivin的反义RNA能够有效的抑制Survivin的表达,从而抑制肿瘤生长,并促进肿瘤细胞凋亡.  相似文献   

10.
目的 探讨外源性Smac/DIABLO对人胰腺癌SW1990细胞生物学特性和对TRAIL及吉西他滨化疗敏感性的影响. 方法 利用脂质体2000介导Smac/DIABLO基因转染胰腺癌SW1990细胞获得细胞SW1990/Smac,转染空载体为对照组(SW1990/neo);在不同浓度和时间下以肿瘤坏死因子相关凋亡诱导配体(TRAIL)和吉西他滨处理2组细胞株并分为TRAIL组、吉西他滨组和联合组.MTT法检测细胞株的生长抑制率,流式细胞仪检测细胞凋亡率及凋亡细胞形态,Western blot检测凋亡相关蛋白Smac/DIABLO、抑制凋亡蛋白XIAP、细胞色素C及细胞凋亡因子caspase-3的表达.结果 转染Smac/DIABLO的细胞生长明显落后于转染空载体的细胞.TRAIL浓度为200、500、1000、2500 ng/ml时,作用24 h对SW1990/neo和SW1990/Smac细胞的抑制率分别为11.11%、46.03%、67.08%、76.19%及22.11%、42.67%、56.63%、67.6% (P <0.05).吉西他滨浓度分别为10、20、40、60μmol/L作用24 h对SW1990/neo和SW1990/Smac的抑制率分别为15.2%、34.6%、55.16%、76.4%和22.65%、36.85%、55.11%、79.99% (P<0.05).以TRAIL(500 ng/ml)、吉西他滨(20 μmol/L)及TRAIL(500 ng/ml)+吉西他滨(20 μmol/L)作用24 h后,SW1990/neo和SW1990/Smac细胞的凋亡率分别为5.64%、15.30%、27.27%和20.37%、23.27%、67.30% (P <0.05).SW1990/Smac细胞在TRAIL及吉西他滨作用后,细胞内促凋亡蛋白Smac/DIABLO、细胞色素C及caspase-3活化片段表达均显著升高,而抑制凋亡蛋白XIAP表达显著降低(P<0.05).结论 Smac/DIABLO可诱导SW1990细胞的凋亡、抑制细胞增殖,并增强胰腺癌细胞对TRAIL及吉西他滨的化疗敏感性,其机制可能与Smac/DIABLO、细胞色素C、XIAP及caspase-3的活性有关.  相似文献   

11.
Background : We investigated the vasopressor hormone response following mesenteric traction (MT) with hypotension due to prostacyclin (PGI2) release in patients undergoing abdominal surgery with a combined general and epidural anesthesia. Methods : In a prospective, randomized, placebo-controlled study we administered 400 mg ibuprofen (i.v.) in 42 patients scheduled for abdominal surgery. General anesthesia was combined with epidural anesthesia (T4-L1). Before as well as 5, 15, 30, 45, and 90 min after MT we recorded plasma osmolality, hemodynamics and measured 6-keto-PGFlα (stabile metabolite of PGI2), TXB2 (stabile metabolite of thromboxane A2) active renin, and arginine vasopressin (AVP) plasma concentrations by radioimmunoassay. Catecholamine levels were assessed by high-pressure liquid chromatography (HPLC) with electrochemical detection. Results : Following MT, arterial hypotension occurred along with a substantial PGI2 release. This was completely abolished by ibuprofen administration. Although plasma levels of 6-keto-PGF (1133 (708) vs. 60 (3) ng/L, median (median absolute deviation), P=0.0001, placebo vs. ibuprofen) remained significantly elevated, blood pressure was restored within 30 min after MT in the placebo group. At the same point in time plasma concentrations of TXB2 (164 (87) vs. 58 (1) ng/L, P=0.0001), epinephrine (46 (33) vs. 14 (6) ng/L, P=0.001), AVP (41 ± (18) vs. 12 (7) ng/L, P=0.0004), and active renin (27 (12) vs. 12 (4) ng/L, P = 0.001) were significantly higher in placebo-treated patients. Conclusion : Under combined general and epidural anesthesia arterial hypotension following MT due to endogenous PGI2 release is associated with enhanced release of AVP, active renin, epinephrine and thromboxane A2, presumably contributing to hemodynamic stability within 30 min after MT.  相似文献   

12.
Don Dame 《Artificial organs》1996,20(5):613-617
Abstract: Virtually all blood pumps contain some kind of rubbing, sliding, closely moving machinery surfaces that are exposed to the blood being pumped. These valves, internal bearings, magnetic bearing position sensors, and shaft seals cause most of the problems with blood pumps. The original teaspoon pump design prevented the rubbing, sliding machinery surfaces from contacting the blood. However, the hydraulic efficiency was low because the blood was able to "slip around" the rotating impeller so that the blood itself never rotated fast enough to develop adequate pressure. An improved teaspoon blood pump has been designed and tested and has shown acceptable hydraulic performance and low hemolysis potential. The new pump uses a nonrotating "swinging" hose as the pump impeller. The fluid enters the pump through the center of the swinging hose; therefore, there can be no fluid slip between the revolving blood and the revolving impeller. The new pump uses an impeller that is comparable to a flexible garden hose. If the free end of the hose were swung around in a circle like half of a jump rope, the fluid inside the hose would rotate and develop pressure even though the hose impeller itself did not "rotate"; therefore, no rotating shaft seal or internal bearings are required.  相似文献   

13.
Abstract: A variety of protein-bound or hydrophobic substances, accumulating as a result of pathologic conditions such as exogenous or endogenous intoxications, are removed poorly by conventional detoxification methods because of low accessibility (hemodialysis), insufficient adsorption capabilities (hemosorption), low efficiency (peritoneal dialysis), or economic limitations (high-volume plasmapheresis). Combining advantages of existing methods with microspheric technology, a module-based system was designed. Major operating parameters of the latter can be modified to allow for adjustment to individual clinical situations. An extracorporeal blood circuit including a plasmafilter is combined with a secondary high-velocity plasma circuit driven by a centrifugal pump. Different microspheric adsorbers can be combined in one circuit or applied in sequence. Thus, a prolonged treatment can be tailored using specially designed selective adsorber materials. Comparing this system with existing methods (high-flux hemodialysis, molecular adsorbent recycling system), results from our in vitro studies and animal experiments demonstrate the superior efficiency of substance removal.  相似文献   

14.
Background : Our objective was to determine whether administration of propranolol or verapamil modifies the hemodynamic adaptation to continuous positive-pressure ventilation (CPPV), in particular the regional distribution of cardiac output (CO).
Methods : General hemodynamics and regional blood flows assessed by microsphere technique (15 (μm) were recorded in 16 anesthetized pigs during spontaneous breathing (SB) and CPPV with 8 cm H2O end-expiratory pressure (CPPV8) before and after intravenous administration of propranolol (0.3 mg · kg−1 followed by 0.15 mg · kg−1 · h−1, n=8) or verapamil (0.1 mg · kg−1 followed by 0.3 mg · kg−1 · h−1, n=8).
Results : CPPV8 depressed CO by 25% without shifts in its relative distribution with the exception of a noteworthy increase in adrenal perfusion. Propranolol increased arterial blood pressure, and due to a fall in heart rate, CO dropped by 25%. The kidneys and, to a lesser extent, the splanchic region and central nervous system received increased fractions of the remaining CO at the expense of skeletal muscle flow. Similar patterns were seen during SB and CPPV8 such that the combination of propranolol and CPPV8 depressed CO by 50%. The circulatory effects of verapamil were less evident but myocardial perfusion tended to increase.
Conclusions : The combination of propranolol or verapamil with CPPV does not result in any specific hemodynamic interaction in anesthetized pigs, except that the combined effect of propranolol and CPPV may severely reduce CO.  相似文献   

15.
Background : Inhibitory effects of volatile anaesthetics on platelet aggregation have been demonstrated in several studies. However, the influence of volatile anaesthetics on intracoronary platelet adhesion has not been elucidated so far.
Methods : Isolated hearts of guinea pigs were perfused with buffer in the absence or presence of volatile anaesthetics (0.5 and 1 MAC) at constant coronary flow rates of 5 ml/min for 25 min, then 1 ml/min for 30 min and again 5 ml/min for 10 min. Before, during and after low-flow perfusion, a bolus of human platelets was applied into the coronary system. To simulate thrombogenic conditions, 0.3 U/ml human thrombin was infused during low-flow perfusion and reperfusion. The number of platelets sequestered to the endothelium was calculated from the difference between coronary in- and output of platelets. The myocardial production of lactate and consumption of pyruvate and coronary perfusion pressure were also determined.
Results : At a flow rate of 5 ml/min only about 3% of the applied platelets did not emerge from the coronary system, in any group. In contrast, 13.1±1.2% (mean±SEM) of infused platelets became adherent in low-flow perfusion in the control group without anaesthetic. The adherence was reduced with each 1 MAC isoflurane (to 6.2±1.2%), sevoflurane (to 4.4±0.9%) or halothane (to 3.2±1.5%) (each P <0.05 vs. control). Volatile anaesthetic, 0.5 MAC, did not inhibit platelet adhesion to a statistically significant extent in any case. Perfusion pressure and metabolic parameters were not statistically different between the control and the hearts exposed to anaesthetics.
Conclusion : Volatile anaesthetics in a concentration of 1 MAC can reduce the adhesion of platelets in the coronary system under reduced flow conditions. This action does not arise from vasodilation or inhibition of ischaemic stress.  相似文献   

16.
Background: Obesity is increasing globallly, including in the formerly "Eastern Bloc" countries. Methods: A survey was made of obesity and bariatric surgery. Results: In the 8 East and Central European countries studied, with total population 300 million, roughly 43% of the population was overweight (BMI 25-30), 23% obese (BMI > 30), with about 15 million people morbidly obese (BMI > 40). From 0-10 morbidly obese individuals/100,000/year undergo bariatric surgery. Conclusion: Most countries were found to provide inadequate treatment for obesity.The majority of the morbidly obese are not treated effectively. However, health-care awareness of obesity and bariatric surgeons are slowly increasing.  相似文献   

17.
Background: It has been shown that the depressive effects of both propofol and midazolam on consciousness are synergistic with opioids, but the nature of their interactions on other physiological systems, e. g. respiration, has not been fully investigated. The present study examined the effect of propofol and midazolam alone and in combination with fentanyl on phrenic nerve activity (PNA) and whether such interactions are additive or synergistic. Methods: PNA was recorded in 27 anaesthetised and artificially ventilated rabbits. In three groups, propofol, fentanyl and midazolam were administered intravenously in incremental doses to construct dose-response curves for the depressant effects of each one on PNA. In another two groups, the effect of pretreatment with either fentanyl 1 μg · kg?1 i. v. or midazolam 0.05 mg · kg?1 i. v. on the effects of propofol and fentanyl respectively on PNA were studied. Results: Propofol and fentanyl caused a dose-dependent depression of PNA with complete abolition at the highest total doses of 16 mg · kg?1 i. v. and 32 μg · kg?1 i. v., respectively. In contrast, midazolam in incremental doses to a total of 0.8 mg · kg?1 reduced mean PNA by 63%, but approximately 12% of PNA remained at a total dose as high as 6.4 mg · kg?1. The mean ED50s, calculated from dose-response curves, were 5.4 mg · kg?1, 3.9 μg · kg?1 and 0.4 mg · kg?1 for propofol, fentanyl and midazolam, respectively. Initial doses of either fentanyl 1 μg · kg?1 i. v. or midazolam 0.05 mg · kg?1 i. v. acted synergistically with subsequent doses of either propofol or fentanyl to abolish PNA at total doses of 8 mg · kg?1 and 8 μg · kg?1, respectively. Conclusion: Fentanyl has a synergistic interaction with both propofol and midazolam on PNA and hence potentially on respiration.  相似文献   

18.
Background: Catecholaminergic support is often used to improve haemodynamics in patients undergoing major abdominal surgery. Dopexamine is a synthetic vasoactive catecholamine with beneficial microcirculatory properties. Methods: The influence of perioperative administration of dopexamine on cardiorespiratory data and important regulators of macro- and microcirculation were studied in 30 patients undergoing Whipple pancreaticduodenectomy. The patients received randomized and blinded either 2 μg · kg?1 · min?1 of dopexamine (n=15) or placebo (n=15, control group). The infusion was started after induction of anaesthesia and continued until the morning of the first postoperative day. Endothelin-1 (ET-1), vasopressin, atrial natriuretic peptide (ANP), and catecholamine plasma levels were measured from arterial blood samples. Measurements were carried out after induction of anaesthesia, 2 h after onset of surgery, at the end of surgery, 2 h after surgery, and on the morning of the first postoperative day. Results: Cardiac index (CI) increased significantly in the dopexamine group (from 2.61±0.41 to 4.57±0.78 1 · min?1 · m?2) and remained elevated until the morning of the first postoperative day. Oxygen delivery index (DO2I) and oxygen consumption index (VO2I) were also significantly increased in the dopexamine group (DO2I: from 416±91 to 717±110 ml/m2 · m2; VO2I: from 98±25 to 157±22 ml/m2 · m2), being significantly higher than in the control group. pHi remained stable only in the dopexamine patients, indicating adequate splanchnic perfusion. Vasopressive regulators of circulation increased significantly only in the untreated control patients (vasopressin: from 4.37±1.1 to 35.9±12.1 pg/ml; ET-1: from 2.88±0.91 to 6.91±1.20 pg/ml). Conclusion: Patients undergoing major abdominal surgery may profit from prophylactic perioperative administration of dopexamine hydrochloride in the form of improved haemodynamics and oxygenation as well as beneficial influence on important regulators of organ blood flow.  相似文献   

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Abstract: Photopheresis is a technique in which peripheral blood mononuclear cells, in the presence of a photoacti-vatable compound, are exposed extracorporeally to ultraviolet A light and reinfused, inducing a host autoregula-tory immune response. Experimental work and ongoing clinical studies are helping to define the role of this novel, safe, and non-toxic immunomodulating technology in the field of transplantation.  相似文献   

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