CDH13表达下调对膀胱癌细胞增殖、克隆形成及PI3K/Akt表达的影响

目的 研究膀胱癌5637细胞中CDHI3表达下调后对细胞增殖、克隆形成及PI3K/Akt表达的影响.方法 应用RNA干扰技术抑制5637细胞中CDH13的表达,细胞克隆形成实验检测细胞克隆形成率,MTT法检测细胞增殖能力,Western Blot检测CDH13、PI3K及Akt的表达水平.结果 膀胱癌5637细胞中CDH13表达下调后细胞克隆形成及增殖能力增强,PI3K及Akt的表达增加.结论 膀胱癌细胞中CDH13表达下调后可能通过激活PI3K/Akt通路促进肿瘤细胞增殖和克隆形成.     

Mu阿片受体抑制肿瘤细胞增殖和促血管生成作用研究进展

Mu阿片受体（Mu opioid receptor, MOR）是阿片类药物的主要作用受体,在肿瘤细胞中高度表达。有研究认为MOR对肿瘤的复发和转移有影响。MOR影响肿瘤复发和转移的作用机制繁杂,不同研究之间也存在争议。文章综述MOR及其亚型对肿瘤细胞的作用,不同的药物浓度差异对肿瘤细胞带来的不同影响,以及MOR通过多种...     

国外期刊摘译

联合应用周期素依赖性蛋白激酶与AKT抑制剂诱导转移性前列腺癌细胞凋亡;肿瘤蛋白D52的表达变化对前列腺癌细胞凋亡与迁移影响的研究;抑制NF-κB与激活AP-1可增强前列腺癌细胞的凋亡;厚朴酚通过抑制EGFR／PI3K／Akt信号通路诱导人前列腺癌细胞凋亡;转移性前列腺癌细胞中PI3K／Akt依赖的转录调控与NF-κB介导的BMP-2-Smad信号通路的激活……     

TRAIL联合HSP90抑制剂17-AAG诱导肝癌细胞凋亡的研究

目的 探讨17-AAG增加TRAIL诱导肝癌细胞HepG2凋亡的分子机制.方法 应用流式细胞仪分析17-AAG联用TRAIL对肝癌细胞HepG2细胞周期的影响;Western blot检测HepG2细胞在17-AAG作用前后凋亡信号传导蛋白Caspase-8、caspa8e-3、c-FLIP、RIP及NF-KB上游调节激酶Akt、IKb-α蛋白的表达变化.结果 联合用药组的细胞生存率为(17.25±2.34)%,显著低于17-AAG单独用药组的[(93.14±5.25)%,P<0.01];17-AAG预处理,随其浓度和时间的增加能明显下调RIP的表达,进而影响Akt的磷酸化,但对c-FLIP的表达无明显影响.结论 TRAIL联合17-AAG可以诱导肝癌细胞凋亡,其机制是通过下调RIP的表达,活化凋亡发生的死亡受体通路及阻断NF-κB通路来实现的.     

PTEN基因转染对人膀胱癌细胞BIU-87中PI3K-Akt信号通路的影响

目的 研究抑癌基因PTEN转染对人膀胱癌细胞BIU-87中PI3K-Akt信号通路的作用.方法 将携有PTEN基因的重组真核表达质粒pBp-PTEN转化大肠杆菌DH5α并扩增,抽提纯化质粒并进行酶切鉴定,pBp-PTEN体外转染BIU-87细胞(pBp-PTEN-BIU87),筛选稳定转染的细胞并扩增培养,以转染了空质粒pBp的BIU-87细胞(pBp-BIU87)和正常BIU-87细胞为对照,用RT-PCR检测PTEN的表达情况.将PTEN基因的真核表达质粒转染膀胱癌细胞BIU-87(pBp-PTEN-BIU87),以BIU87细胞和pBp-BIU87细胞为对照,应用Wester blot方法 检测三组细胞P110(PI3K的催化亚单位)、磷酸化P110、Akt和磷酸化Akt表达的情况.结果 3种细胞P110和Akt蛋白总水平没有变化,但磷酸化P110和磷酸化Akt在PTEN转染细胞中的表达明显弱于对照组.结论 PTEN是通过对PI3K-Akt信号传导途径的负调控而抑制肿瘤的形成.PTEN-PI3K-Akt途径可能是PTEN抑癌作用的重要机制.     

信号通路在肝细胞癌发展中的作用

目的 探讨EGFR信号通路、MAPK信号通路、IKB/NF-κB信号通路、PI3K/Akt信号通路、WNT/β-catenin信号通路和Hedgehog信号通路在肝细胞癌发展中的作用。方法 采用文献复习的方法,对信号通路在肝细胞癌发展中作用的相关文献进行综述。结果 在肝癌的发生发展过程中,EGFR、MAPK、IKB/NF-κB、PI3K/Akt、WNT/β-catenin、Hedgehog等信号通路之间复杂交织和相互作用,并且可能存在一些肿瘤标志物、抑癌基因、原癌基因和miRNA的协同作用。结论 分子信号通路的异常改变是肿瘤发生及发展的必要条件,并且信号通路在肝细胞癌发病中有着复杂的交叉和冗余。     

PI3K/Akt途径在前列腺癌中的治疗前景

磷脂酰肌醇-3羟基激酶/蛋白激酶B(PI3K/Akt)信号通路是肿瘤、炎症等发生发展过程中一条重要的信号通路。研究发现,在许多肿瘤组织中,PI3K/Akt信号通路的活化和过度表达与肿瘤的发生发展密切相关。在前列腺癌中,这种途径的激活似乎是许多侵袭性前列腺癌的特征。该途径的生物标志物将其与疾病进展风险相关联。本文回顾了PI3K/Akt途径的共同靶向方法的基本原理和相关性,以期通过更好地了解前列腺癌中PI3K/Akt途径的生物学特征,相关生物标志物和联合治疗来优化该靶向途径,从而改善侵袭性前列腺癌患者的结局。     

血管紧张素Ⅱ对增生性瘢痕成纤维细胞PI3K/Akt信号通路的影响

目的 观察血管紧张素Ⅱ(angiotensin Ⅱ,Ang Ⅱ)对增生性瘢痕成纤维细胞磷脂酰肌醇-3激酶/蛋白激酶B(phosphoinositide 3-kinase/Akt,PI3K/Akt)信号通路的影响.方法 体外培养人增生性瘢痕成纤维细胞,用免疫荧光组织化学染色检测细胞Ang Ⅱ受体AT,和AT_2的表达.以PI3k活性测定法和Western Blotting法检测细胞PI3K的活性和Akt的磷酸化.结果 免疫荧光组织化学染色结果显示培养的增生性瘢痕成纤维细胞同表达AT_1和AT_2受体.Ang Ⅱ(10~(-9)～10~(-7)mol/L)刺激可增加细胞Akt的磷酸化和P13K的活性.AT_2受体拮抗剂PD1233191可显著增强AngⅡ诱导的细胞Akt磷酸化和PDK活性增加(P<0.05);AT_1受体拮抗剂Valsartan可显著抑制AngⅡ诱导的细胞Akt磷酸化和PDK活性增加(P<0.05).结论 Ang Ⅱ通过其受体AT_1和AT_2可调控增生性瘢痕成纤维细胞Akt磷酸化和PI3K的活性.     

抑制PI_3 K/Akt信号通路对Ephrin-A1介导的肝癌细胞运动和侵袭能力的影响

目的 探讨PI_3K/Akt信号传导通路在Ephrin-A1介导的肝癌细胞侵袭、转移过程中的作用.方法 Western blot法检测Ephrin-A1/Fc融合蛋白作用人肝癌细胞系Huh-7细胞前后丝裂原激活的蛋白激酶(MAPK)和磷脂酰肌醇3激酶(PI_3K)信号分子的表达,利用LY294002特异性的阻断PI_3K/Akt信号通路后,检测细胞运动能力、细胞侵袭能力的变化.结果 Ephrin-A1/Fc融合蛋白作用后p-Akt磷酸化蛋白的表达与对照组比较明显上升(t=4.564,P＜0.05),PI_3K/Akt信号通路可能为Ephrin-A1/EphA1作用的下游信号传导通路;LY294002明显抑制Ephrin-A1/Fc融合蛋白对Huh7细胞中PI_3K/Akt信号通路的激活,p-Akt磷酸化蛋白的含量与对照组比较明显减少(P＜0.05);Ephrin-A1介导肝癌细胞的运动能力及侵袭能力明显受到抑制(P＜0.05). 结论 PI_3K/Akt信号通路在Ephrin-A1介导的肝癌细胞侵袭、转移过程中起重要的作用.     

肝细胞生长因子及其受体在膀胱癌中的表达及意义

目的探讨肝细胞生长因子及其受体c-Met在人膀胱移行细胞癌中的表达及临床意义。方法采用免疫组化方法检测8例正常膀胱黏膜标本及45例膀胱移行细胞癌标本中HGF及c-Met的表达;并以分级、分期、复发、转移等临床特征分组,比较各组的阳性表达率。结果8例正常膀胱黏膜中HGF均为阴性表达,c-Met仅1例为弱阳性表达。而45例膀胱移行细胞癌标本中,两者阳性表达率分别为64.4%和62.2%,共表达率42.2%。肿瘤组织与正常膀胱黏膜比较,HGF及c-Met的表达差异均有统计学意义。肿瘤初发和复发组HGF阳性表达率差异有统计学意义(P<0.01);Tis~T1组及T2~T4组c-Met的阳性表达率差异有统计学意义(P<0.01)。结论HGF及其受体c-Met在膀胱移行细胞癌中呈过度表达,该信号传导通路主要以自分泌方式激活,在膀胱移行细胞癌的发生、发展及术后复发中可能起重要作用。     

Vasopressor hormone response following mesenteric traction during major abdominal surgery

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_1α (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.     

A Teaspoon Pump for Pumping Blood with High Hydraulic Efficiency and Low Hemolysis Potential

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.     

Microspheres Based Detoxification System: A New Method in Convective Blood Purification

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.     

Tissue perfusion in relation to cardiac output during continuous positive-pressure ventilation and administration of propranolol or verapamil

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.     

Volatile anaesthetics reduce adhesion of blood platelets under low-flow conditions in the coronary system of isolated guinea pig hearts

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.     

Bariatric Surgery in Some "Central and East-European (former Eastern bloc)"Countries - Current Status and Prediction for the Next Millennium

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.     

Is the recovery profile of mivacurium independent of the rate of decay of its plasma concentration in patients with normal plasma cholinesterase activity?

Background: The duration of action of muscle relaxants is poorly correlated to the rate of decay of their plasma concentration. The plasma concentration of mivacurium may rapidly decrease below its active concentration because of the extensive hydrolysis of mivacurium. By inflating a tourniquet on one upper limb for 3 min after the administration of atracurium, mivacurium or vecuronium, we studied the influence of the initial decline of their plasma concentration on their effect. Methods: In 50 patients anaesthetised with thiopental, isoflurane and fentanyl, the effect of bolus doses of 0.15 or 0.25 mg . kg^?1 mivacurium (MIV 15, MIV 25), 0.3 or 0.5 mg . kg^?1 atracurium (ATR 30, ATR 50) and 0.06 or 0.1 mg . kg^?1 vecuronium (VEC 06, VEC 10) were measured on both arms (evoked response of the adductor pollicis to train-of-four stimulation every 12 s), a tourniquet being applied on one arm just before and during 3 min after the muscle relaxant bolus. Results: Tourniquet inflation of 3 min almost abolished the neuromuscular effect of mivacurium. In the vecuronium groups and in the ATR 50 group, tourniquet inflation did not modify the maximum degree of depression of the twitch response. Also, the duration of action of vecuronium was unaffected by the tourniquet. In the ATR 30 group, times to return of the twitch response to 25% (duration 25%) and 75% (duration 75%) of control response were significantly shorter in the cuffed arm, 23 min vs 27 min, and 41 min vs 45 min, respectively. In the ATR 50 group, only duration 25% was significantly shorter in the cuffed arm (41 min vs 45 min). Conclusion: The results suggest that the rate of decline of the plasma concentration of mivacurium is so rapid, that a very low and almost clinically ineffective concentration is present as soon as 3 min after its administration. The results also indicate that the recovery from a mivacurium-induced neuromuscular blockade is not influenced by the rate of decay of its plasma concentration in patients with genotypically normal plasma cholinesterase.     

Membranes in Artificial Organs

Abstract: Membrane processes play a pivotal and enabling role in modern replacement therapy for acute and chronic organ failure and in the management of immunologic diseases. In fact, virtually all contemporary extracorporeal blood purification methods employ membrane devices, and the next generation of artificial organs and tissue engineering therapies are almost certain to be similarly grounded in membrane technology. In this short essay, we comment on the similarities and differences among synthetic membranes and their natural counterparts and also provide a critical overview of the demographics and technology of hemodialysis, hemofiltration, apheresis, oxygenation, and emerging membrane technologies and applications.     

Synergistic interaction between the effects of propofol and midazolam with fentanyl on phrenic nerve activity in rabbits

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.     

Influence of dopexamine hydrochloride on haemodynamics and regulators of circulation in patients undergoing major abdominal surgery

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.