应用奥曲肽预防胰十二指肠切除术后胰漏作用的研究

目的:预防性使用奥曲肽是否能减少胰十二指肠切除术后胰漏发生率存在着争议。本研究旨在研究奥曲肽在不同胰腺情况下预防胰十二指肠切除术后胰漏发生的作用。方法:本研究将"软胰腺"、"细胰管"作为术后胰漏发生的高危险因素,将184例胰十二指肠切除术病例分为4组:低危险/非奥曲肽组、低危险/奥曲肽组、高危险/非奥曲肽组、高危险/奥曲肽组。观察术后胰漏等术后并发症情况。结果:共发生术后胰漏35例(19%),其中高危险组胰漏发生率是低危险组2倍以上(27%versus 10%,P<0.01)。在胰漏发生低危险胰腺情况下,奥曲肽组与非奥曲肽组术后胰漏发生无显著差别;在胰漏发生高危险胰腺情况下,奥曲肽能显著降低术后胰漏发生率。结论:在胰十二指肠切除术围手术期应根据胰腺的具体情况选择性使用奥曲肽既能有效预防术后胰漏的发生,又能避免不必要的浪费。     

兰索拉唑联合奥曲肽治疗急性非静脉曲张性上消化道出血的临床效果及安全性分析

目的:探讨兰索拉唑联合奥曲肽治疗急性非静脉曲张性上消化道出血的临床疗效以及安全性。方法:选取自2014年1月到2017年1月我院收治的急性非静脉曲张性上消化道出血患者102例,随机分为A组、B组和C组,每组各34例。A组使用兰索拉唑进行治疗,B组使用奥曲肽进行治疗,C组联合使用兰索拉唑和奥曲肽进行治疗。对比三组患者的临床疗效、止血时间、血压稳定时间、胃管引流量、胃液PH值以及不良反应的发生情况。结果:治疗后,C组的显效率为61.76%,显著高于A组和B组(均P0.05);C组的总有效率为97.06%,显著高于B组(P0.05);C组的止血时间为(15.37±4.38)h,血压稳定时间为(7.23±1.18)h,胃管引流量为(236.59±29.81)mL,均显著少于A组和B组,而胃液PH值为(5.91±0.57),显著高于A组和B组(均P0.05)。三组患者不良反应发生率的对比差异均没有统计学意义(P0.05)。结论:兰索拉唑联合奥曲肽治疗急性非静脉曲张性上消化道出血可显著提高止血效果,临床疗效明显优于单用兰索拉唑或奥曲肽治疗,且安全性相当。     

A molecular dynamics simulation investigation of the relative stability of the cyclic peptide octreotide and its deprotonated and its (CF3)-Trp substituted analogs in different solvents

The cyclic octa-peptide octreotide and its derivatives are used as diagnostics and therapeutics in relation to particular types of cancers. This led to investigations of their conformational properties using spectroscopic, NMR and CD, methods. A CF₃-substituted derivative, that was designed to stabilize the dominant octreotide conformer responsible for receptor binding, turned out to have a lower affinity. The obtained spectroscopic data were interpreted as to show an increased flexibility of the CF₃ derivative compared to the unsubstituted octreotide, which could then explain the lower affinity.In this article, we use MD simulation without and with time-averaged NOE distance and time-averaged local-elevation ³J-coupling restraining representing experimental NMR data to determine the conformational properties of the different peptides in the different solvents for which experimental data are available, that are compatible with the NOE atom–atom distance bounds and the ³J_HNHα-couplings as derived from the NMR measurements. The conformational ensembles show that the CF₃ substitution in combination with the change of solvent from water to methanol leads to a decrease in flexibility and a shift in the populations of the dominant conformers that are compatible with the experimental data.     

Cytoplasmic expression of SSTR2 and 5 by immunohistochemistry and by RT/PCR is not associated with the pharmacological response to octreotide

ObjectiveTo evaluate expression of somatostatin receptor subtypes 2 and 5 (SSTR 2 and 5) by RT/PCR and immunohistochemistry (IHC) in GH-secreting adenomas, seeking correlations with response to octreotide.MethodsSSTR2 and 5 expression was tested by IHC (n = 37), RT/PCR (n = 36) or both (n = 13) in GH-secreting adenomas from 60 patients with acromegaly who had undergone pituitary surgery; 36 had been treated preoperatively with octreotide LAR for 3–6 months, and were categorized as responders (achievement of GH <2.5 ng/mL and a normal age-adjusted IGF-1), partial responders (GH and IGF-1 reduction >50% and >30%, respectively) or non-responders. IHC was performed on a tissue microarray using specific antibodies directed to the carboxyl terminus of SSTR2 and 5.ResultsSSTR5 was the predominantly expressed receptor subtype by both IHC and RT/PCR in all tumors tested, regardless of whether they came from octreotide-naïve, octreotide-responsive, or octreotide-resistant patients. Immunostaining was concentrated in the cytoplasm. Neither SSTR2 nor SSTR5 expression correlated with baseline or post-octreotide GH or IGF-1 levels or tumor volume by either method. The agreement rate between RT/PCR and IHC was 77% in all 13 adenomas in which both methods were used.ConclusionExpression of these receptors does not guarantee an adequate response to somatostatin analogs; other functional aspects of this interaction, such as receptor homo- and heterodimerization, and the resulting signaling cascade, probably play a role in determining whether a patient will respond or not to these agents.     

选择性环氧合酶-2抑制剂联合奥曲肽诱导人胃癌细胞的凋亡

目的探讨选择性环氧合酶-2抑制剂NS-398与奥曲肽联合应用对人胃癌细胞株BGC-823生长、凋亡的影响。方法体外培养BGC-823细胞,分别用NS-398(100μmol/L)与奥曲肽(1μmol/L)单独及联合处理不同时间后,倒置显微镜观察细胞形态学变化;观察生长曲线的变化;流式细胞仪检测细胞凋亡率;实时定量(Real-time)PCR检测COX-2mRNA的表达;Western blot法检测Caspase-3蛋白表达。结果倒置显微镜下,对照组BGC-823细胞生长良好,药物处理后,细胞变小、变圆,悬浮,联合组细胞形态学改变显著强于单纯用药组;药物作用后,细胞生长受抑制,出现负增长,联合组作用明显强于单纯用药组;流式细胞仪检测表明联合用药组诱导BGC-823细胞的凋亡率明显高于单一用药组和对照组(P0.01);各处理组均使BGC-823细胞COX-2mRNA表达下调(P0.05);药物处理后细胞Caspase-3蛋白表达明显增加。结论 NS-398、奥曲肽联合可协同抑制BGC-823细胞生长、增殖,其机制可能与下调COX-2mRNA表达、诱导肿瘤细胞凋亡相关。     

Design,synthesis and biological activity of cell‐penetrating peptide‐modified octreotide analogs

Four novel octreotide analogs with cell‐penetrating peptides (CPPs) at the N‐terminus or C‐terminus were synthesized by a stepwise Fmoc solid‐phase synthesis strategy. The synthesized peptides were analyzed and characterized using reverse phase HPLC and MALDI‐TOF mass spectrometry. The antiproliferative activity of the analogs was tested in vitro on human gastric (SGC‐7901) and hepatocellular cancer (BEL7402) cell lines using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay. Interestingly, these analogs showed a higher anticancer activities than the parent octreotide except CMTPT03 analog. The results demonstrate that the designed octreotide analogs enhance their anticancer activity after linking together the CPPs to octreotide at the N‐terminus, and are potential molecules for future use in cancer therapy and drug targeting. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd.     

丙氨酰谷氨酰胺联合奥曲肽对重症急性胰腺炎患者的临床疗效

目的:探讨丙氨酰谷氨酰胺(Ala-Gln)联合奥曲肽治疗重症急性胰腺炎(SAP)的临床疗效及对患者血清白细胞介素-6(IL-6)、C反应蛋白(CRP)水平及相关生化指标的影响。方法:选取我院2013年1月~2016年12月收治的100例SAP患者,根据随机数字表法均分为两组。对照组仅予以奥曲肽治疗,观察组给予Ala-Gln联合奥曲肽治疗。记录比较两组的临床疗效、治疗前后血清IL-6、CRP、淀粉酶(AMY)、乳酸脱氢酶(LDH)、前清蛋白(PA)和白蛋白(ALB)水平的变化情况。结果:治疗10 d后,观察组总有效率为88.0%,明显高于对照组的64.0%(P0.05)。两组治疗10 d后血清IL-6、CRP、AMY、LDH水平均显著低于治疗前(P0.01),且与对照组对比,观察组血清IL-6、CRP、AMY、LDH水平的改善程度均更为显著(P0.01)。与治疗前相比,两组治疗10 d后血清PA、ALB水平均明显上升(P0.05),且观察组治疗10 d后血清PA和ALB水平的改善程度均显著优于对照组(P0.01)。结论:丙氨酰谷氨酰胺联合奥曲肽治疗更能有效消除或缓解重症急性胰腺炎患者的症状与体征,控制机体炎症反应,提高营养代谢水平,改善预后。     

Reactions of PtII diamine anticancer complexes with trypanothione and octreotide

The products formed in reactions of the square-planar platinum(II) anticancer complexes, [Pt(en)Cl₂] and [Pt(R,R-dach)Cl₂] where en = ethylenediamine and dach = diaminocyclohexane, with trypanothione, a glutathione analogue found in some parasites, and octreotide, a synthetic analogue of the hormone somatostatin, have been investigated. Mononuclear and binuclear platinum adducts were formed in reactions of the cyclic disulfides in their oxidised and reduced forms, and were analysed by UV–visible spectroscopy and liquid chromatography–mass spectrometry (LC–MS). NMR and molecular modelling studies were carried out on the mononuclear adducts.     

生长抑素类似物治疗肿瘤化疗相关性腹泻的临床观察

目的评价生长抑素类似物(奥曲肽,下同)对肿瘤化疗相关性腹泻的疗效。方法对58例出现化疗相关性腹泻(CID)的患者给予奥曲肽治疗。按照NCI CTC标准,全组患者出现Ⅱ级腹泻12例,Ⅲ级腹泻38例,Ⅳ级腹泻8例。Ⅱ级、Ⅲ级CID给予皮下注射奥曲肽100μg bid或静脉持续泵入奥曲肽25μg/h,每天8 h,Ⅳ级CID给予静脉持续泵入奥曲肽25μg/h,每天12 h。结果全组58例患者的总有效率为89.7%。Ⅱ级CID奥曲肽治疗平均有效时间为2.6 d;Ⅲ级CID皮下注射奥曲肽的治疗有效时间平均为4.7 d,而静脉持续泵入奥曲肽的治疗天数平均为3.9 d,二者差异有统计学意义(P<0.05);Ⅳ级CID静脉持续泵入奥曲肽治疗平均有效时间为7.5 d。不良反应表现为5例皮下注射的患者出现一过性面部潮红,恶心,未作处理自行缓解。结论奥曲肽能有效地控制肿瘤化疗相关性腹泻,Ⅱ级以上CID患者宜采用静脉持续滴注治疗为宜。     

奥曲肽治疗急性粘连性肠梗阻疗效观察

目的:探讨生长抑素对腹部手术后急性粘连性肠梗阻的治疗作用。方法:70例急性粘连性肠梗阻患者随机分为观察组与对照组各35例。对照组予胃肠减压、灌肠、补液及抗感染治疗等常规治疗;观察组在此基础上加用奥曲肽(生长抑素类似物)0.1 mg皮下注射,每8h一次,治疗72 h。观察两组患者腹痛评分、腹痛缓解时间、胃肠减压量、肛门恢复排气时间、立卧位腹部平片、临床缓解情况。结果:观察组34例(97.1%)临床缓解,明显高于对照组的28例(80.0%)(P<0.05)。与对照组相比,观察组在治疗第1、2天后腹痛评分明显下降(均为P<0.01),腹痛缓解时间显著缩短(P<0.01),治疗第1、2、3天的胃肠减压量均显著减少(均为P<0.01),恢复排气时间也明显缩短(P<0.01)。结论:急性粘连性肠梗阻在常规治疗基础上加用生长抑素,可明显改善临床症状,提高疗效。