生长抑素及Octreotide对急性胰腺炎胰腺细胞凋亡的作用机制

目的 :探讨生长抑素 (SS)及其类似物 (Octreotide)治疗小鼠急性胰腺炎对胰腺细胞凋亡及凋亡调控基因 bax、p5 3的作用。方法 :以雨蛙肽诱导 CD 1小鼠急性胰腺炎模型 ,并应用细胞凋亡原位标记检测(TU NEL)染色、免疫组化技术等检测胰腺细胞凋亡及凋亡调控基因 bax、p5 3的蛋白表达 ,以及生长抑素及其类似物治疗后对胰腺细胞凋亡及凋亡调控基因 bax和 p5 3蛋白表达的影响。结果 :HE染色见胰腺组织中典型的细胞核固缩及凋亡小体形成。 SS治疗后 1小时及 Octreotide治疗后 5、14小时胰腺细胞凋亡指数显著高于非治疗组 1、5和 14小时各时间点 (P均 <0 .0 1)。正常胰腺组织未见凋亡调控基因 bax、p5 3的表达 ,SS治疗后1小时胰腺细胞 p5 3染色阳性率明显高于非治疗组 ,P<0 .0 1,而非治疗组和 SS治疗组 1小时的胰腺细胞 bax染色阳性率无显著差异 ;Octreotide治疗后 5、14小时胰腺细胞 bax染色阳性率明显高于非治疗组相应时间点 ,P均 <0 .0 1,而非治疗组和 Octreotide治疗组 5、14小时的胰腺细胞 p5 3染色阳性率无显著差异。结论 :生长抑素及其类似物治疗急性胰腺炎的相同机制之一可能是诱导损伤的胰腺细胞凋亡以减轻炎症反应 ,但前者诱导胰腺细胞凋亡机制可能与凋亡调控基因 p5 3的表达有关而与 bax的表达无关 ;

肿瘤生长抑素受体显像剂^(99)Tc^m-octreotide的制备及鉴定

目的 建立99Tcm 直接标记octreotide的最佳方法 ,评价其受体介导结合特性以及作为肿瘤生长抑素受体显像剂的可能性。方法 采用抗坏血酸钠和连二亚硫酸钠作为还原剂 ,对oct reotide进行标记 ;用大鼠脑皮质细胞膜进行体外受体结合分析 ;进行动物体内分布、药代动力学、毒性实验和临床受体显像。结果 99Tcm octreotide放化纯达 78 5 % ,纯化后为 93 8% ,室温下放置 4h为92 1%。细胞膜体外放射受体结合分析证实99Tcm octreotide与octreotide具有相同的受体介导结合特性。 3例肺癌患者临床受体显像均获得阳性结果。结论 99Tcm 直接法标记octreotide方法可行 ,稳定性好 ;99Tcm

^(99)Tc^m直接法标记Octreotide

建立了 99Tcm直接标记 Octreotide的方法 ,并选出了最佳标记条件。在最佳标记条件下 ,标记率为 78.6 % ,纯化后放化纯度为 93.8%。纯化后的标记物室温下放置 4 h,或分别与过量 DTPA、HSA和 L-半胱氨酸 37℃孵育 4 h,其放化纯度为 92 .1%～ 93.6 % ,无显著改变。 99Tcm 直接标记Octreotide方法可行 ,标记肽稳定性好 ,可望用于生长抑素受体显像。

NCI-H446细胞的^(125)Ⅰ-[Tyr^3]octreotide受体分析

目的 :探讨小细胞肺癌与 [Tyr3 ]octreotide (TOC)的亲和力。方法 :用氯胺T方法标记的12 5I-TOC作为配基 ,检测小细胞肺癌细胞株NCl-H4 4 6与其结合的受体位点数及亲和常数。结果 :氯胺T法标记的12 5I-TOC经SephadexG - 10纯化后放化纯大于 95 % ;受体分析显示NCI-H4 4 6表达的生长抑素受体多 (Bmax =1 17× 10 5受体位点 /细胞 ) ,与12 5I-TOC亲和力强 (Kd =0 5 8nM)。结论 :TOC的标记物可用于小细胞肺癌肿瘤的受体显像及放射治疗。

Octreotide的^(131)I标记及Graves眼病炎症细胞的体外摄取

将octreotide中的苯丙氨酸用酪氨酸替换合成[Tyr3]octreotide,对其进行了131I标记。考察了氯胺T标记法中氯胺T和[Tyr3]octreotide的用量对标记率的影响,观察了Graves眼病相关炎症细胞对131I-[Tyr3]octrotide的体外摄取情况。结果表明,对octreotide进行结构修饰后得到的[Tyr3]octreotide可以用于131I标记;氯胺T法对[Tyr3]octreotide进行131I标记时,氯胺T和[Tyr3]octreotide的最佳用量分别为1.6和1.4μg,最高标记率为85%;T淋巴细胞、活化的成纤维细胞及血管内皮细胞均能够摄取131I-[Tyr3]octreoti-de,而脂肪细胞的摄取则明显较少。以上结果表明,131I-[Tyr3]octreotide能够被Graves眼病发病过程中的炎症细胞摄取,具有用于Graves眼病发病过程中炎症反应程度评估的应用潜力。但由于摄取量还很小,需要进一步深入研究。

^(188)Re直接标记octreotide的方法学

188Re标记octreotide可用直接标记法或间接标记法。直接标记法包括预锡化法和分步还原法,分步还原法需先用还原剂还原octreotide,然后用SnCl2还原188ReO4-进行直接标记;预锡化法则直接以SnCl2还原octreotide和188ReO4-,打开octreotide分子内双硫键,使188Re直接标记octreotide。预锡化直接标记法简便快速,能够得到较高的放化纯度,无须进一步纯化,适合用于制备药盒。

非小细胞肺癌荷瘤鼠^(99m)Tc-acetate-octreotide显像与生长抑素受体表达水平的实验研究

目的:探讨非小细胞肺癌(NSCLC)荷瘤鼠模型肿瘤组织中生长抑素受体(SSTR)的表达水平与99mTc-acetate-octreotide显像的相关性研究。方法:体外培养NSCLC细胞株SPC-A1,种植于balb/c裸鼠皮下成瘤,建立人NSCLC荷瘤鼠模型;行99mTc-acetate-octreotide显像,勾画ROI计算肿瘤与对侧正常组织(N/NT)放射性比值,并测定肿瘤及主要脏器单位组织的放射性摄取百分值(%ID/g),采用逆转录-聚合酶反应(RT-PCR)检测肿瘤组织中各SSTR亚型mRNA的表达水平,对SSTR亚型表达水平与T/NT放射性摄取比值进行相关性研究。结果:99mTc-acetate-octreotide NSCLC荷瘤鼠模型显像示肿瘤部位有较高的放射性浓聚,与对侧正常组织T/NT比值较高,4h达2.38±0.09;99mTc-acetate-octreotide荷瘤鼠体内生物学分布示药物在肿瘤部位有较高的摄取;RT-PCR示NSCLC组织中有着丰富的SSTR表达,SSTR3、SSTR5亚型表达水平较高,其中SSTR5的mRNA表达水平与肿瘤显像阳性荷瘤鼠T/NT比值呈正相关(r=0.93,P<0.01)。结论:NSCLC细胞株SPC-A1高表达SSTR3和SSTR5,其中SSTR5表达水平与肿瘤组织对99mTc-acetate-octreotide的摄取呈正相关。99mTc-acetate-octreotide受体显像对NSCLC有较好的影像诊断价值。

Efficacy of octreotide in the prevention of complications after pancreaticoduodenectomy in patients with soft pancreas and non-dilated pancreatic duct: A prospective randomized trial

Background: The efficacy of octreotide to prevent postoperative pancreatic fistula(POPF) of pancreaticoduodenectomy(PD) is still controversial. This study aimed to evaluate the effect of postoperative use of octreotide on the outcomes after PD.Methods: This is a prospective randomized controlled trial for postoperative use of octreotide in patients undergoing PD. Patients with soft pancreas and pancreatic duct < 3 mm were randomized to 2 groups.Group I did not receive postoperative octreotide. Group II received postoperative octreotide. The primary end of the study is to compare the rate of POPF.Results: A total of 104 patients were included in the study and were divided into two randomized groups.There were no significant difference in overall complications and its severity. POPF occurred in 11 patients(21.2%) in group I and 10(19.2%) in group II, without statistical significance(P = 0.807). Also, there was no significant differences between both groups regarding the incidence of biliary leakage(P = 0.083), delayed gastric emptying(P = 0.472), and early postoperative mortality(P = 0.727).Conclusions: Octreotide did not reduce postoperative morbidities, reoperation and mortality rate. Also, it did not affect the incidence of POPF and its clinically relevant variants.

Effects of octreotide on gallbladder pressure and myoelectric activity of Oddi sphincter in rabbits

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Pathological changes in multiple organs of rats with severe acute pancreatitis treated by baicalin and octreotide

BACKGROUND:Severe acute pancreatitis(SAP)features fatal pathogenetic conditions and high mortality rate.The study of SAP complicated with multiple organ injuries is of important significance.In this study,we explored the protective effect of baicalin on multiple organs of SAP rats and compared it with that of octreotide through light and electron microscopic observations of the pathological changes. METHODS:The improved Aho method was used to prepare SAP rat models.These rats were then randomly divided into a sham-operated group(n=45),a model control group(n=45), baicalin-treated group(n=45)and octreotide-treated group (n=45).Based on the difference in time points after operation, these groups were subdivided into 3,6 and 12 hour subgroups (n=15).At the corresponding time point after operation,the mortality rate of rats was recorded,and then the rats were humanely killed to take samples of multiple organs that were subsequently examined for pathological changes under light and electron microscopy. RESULTS:At 12 hours after operation,the mortality rate of rats in the baicalin-and octreotide-treated groups was lower than that in the model control group(P【0.05).Compared to the model control group,the pathological changes and pathological scores in the baicalin-and octreotide-treated groups were mitigated and relieved to varying degrees.The pathological changes under electron microscopy were also improved.CONCLUSIONS:Both baicalin and octreotide show good protective effects on multiple organs of SAP rats.Baicalin as a new drug has good prospects in the treatment of SAP.

Effect of Octreotide on cell-cycle kinetics and serum CEA level in hepatic metastases of colonic adenocarcinoma

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Effect of octreotide on angiogenesis induced by hepatocellular carcinoma in vivo

OBJECTIVE: To investigate the effect of somatostatin analogue octreotide on angiogenesis induced byhepatocellular carcinoma (HCC) in vivo.METHODS: LCI-D20 corneal micropocket model in nude mouse was used to dynamically observeangiogenesis under a stereoscopic zoom microscope and a digital camera system and to evaluate the effectof octreotide on angiogenesis. Male nude mice were subcutaneously implanted with LCI-D20 tumor tissuesfor tumor xenograft studies. Microvessel density in CD34-stained tumor sections was analyzed byimmunohistochemical SP method.RESULTS: Tumor tissues from LCI-D20 implanted into the corneal micropocket induced angiogenesis.When animals received systemic octreotide treatment, angiogenesis response in the cornea of mice wasmoderate, the appearance of vascular buds was delayed, and the new capillaries were sparse and grewslowly. Compared with the control group, the neovascularization induced by HCC in the cornea of micewas markedly inhibited on day 7, 9, 12, 15, 18 and 21 after implantation in the octreotide-treated group(P【0.05). Systemic administration of octreotide produced a significant suppression of the growth ofLCI-D20. Immunohistochemical studies of tumor tissues revealed decreased microvessel density in theoctreotide-treated animals as compared with the controls (21.7±4.27 versus 31.8±3.87, P【0. 01).CONCLUSION: Somatostatin analogue octreotide is able to inhibit angiogenesis induced by HCC invivo and may provide a new approach to the treatment of HCC.

Octreotide-induced acute life-threatening gallstones after vicarious contrast medium excretion:A case report

BACKGROUND Octreotide is widely used for the treatment of acromegaly,neuroendocrine tumors,and secretory diarrhea.However,long-term octreotide treatment can increase the incidence of gallstones.Vicarious contrast medium excretion(VCME)through the hepatobiliary system is well known.However,few studies have reported octreotide-induced acute gallstones following VCME.CASE SUMMARY A 69-year-old man presented with left lower back pain and hematuria caused by a fall.The patient had a history of polycystic kidney disease.VCME occurred following renal artery embolization for a ruptured polycystic kidney.After 5 d of treatment with octreotide,the patient developed acute gallstones and intrahepatic cholestasis which further induced pancreatitis and cholangitis.He was discharged after hemodialysis,antibiotics,and supportive treatments.CONCLUSION For patients with a high-risk of VCME,octreotide should be cautiously administered and carefully monitored.

Pancreatic parenchymal injection of ethanol and octreotide to induce focal pancreatic fibrosis in rats: Strategies to eliminate postoperative pancreatic fistula

Background: Postoperative pancreatic fistula(POPF) is more likely to occur in a soft pancreas compared to a hard pancreas in which fibrosis has progressed. There is almost no leakage at the anastomosis site or cut surface of a hard pancreas. The aim of this study was to induce localized fibrosis at the cut surface of the pancreas in a rat model.Methods: Thirty-six rats were divided into three groups(group S: normal saline group; group E: ethanol group; and group O: octreotide group). Each rat was directly injected with a particular compound at the duodenal lobe of the pancreatic parenchyma. Each group was divided into three subgroups according to the time of post-injection sacrifice(1, 2, or 4 weeks). The hardness, suture holding capacity(SHC), and histological fibrosis grade of each pancreas were measured.Results: The hardness, SHC, and fibrosis grade of groups E and O were increased at week 1, with greater increases in group E(all P < 0.001). In a subgroup comparison, the hardness, SHC, and fibrosis grade of group E tended to decrease gradually over time, with no regular pattern evident in group O. A comparison between the injected site(duodenal lobe) and non-injected site(splenic lobe) of the pancreas revealed increases in the three parameters of group E only in the duodenal lobe, with increases in group O at both the duodenal and splenic lobes.Conclusions: Parenchymal injection of ethanol and octreotide increased pancreatic fibrosis. Unlike octreotide, ethanol provoked localized fibrosis that was maintained over time. It is expected that ethanol injection could eliminate POPF during pancreatic surgery.

Role of octreotide in small bowel bleeding

Gastrointestinal bleeding accounts for a drastic negative impact on the quality of the patients’lives as it requires multiple diagnostic and therapeutic interventions to identify the source of the bleeding.Small bowel bleeding is the least common cause of gastrointestinal bleeding.However,it is responsible for the majority of complaints from patients with persisting or recurring bleeding where the primary source of bleeding cannot be identified despite investigation.A somatostatin analog known as octreotide is among the medical treatment modalities currently used to manage small bowel bleeding.This medication helps control symptoms of gastrointestinal bleeding by augmenting platelet aggregation,decreasing splanchnic blood flow,and antagonizing angiogenesis.In this review article,we will highlight the clinical efficacy of octreotide in small bowel bleeding and its subsequent effect on morbidity and mortality.

Systematic literature review of the antitumor effect of octreotide in neuroendocrine tumors

AIM To provide a comprehensive examination of the existing evidence of the antitumor effect of long-acting octreotide in neuroendocrine tumors(NETs).METHODS A systematic literature review of clinical trials and observational studies was conducted in PubM ed, EMBASE, and Cochrane through January 18, 2017. Conference abstracts for 2015 and 2016 from 5 scientific meetings were also searched.RESULTS Of 41 articles/abstracts identified, 13 unique studies compared octreotide with active or no treatment. Two of the 13 studies were clinical trials; the remaining were observational studies. The phase 3 Placebo-Controlled, Double-Blind, Prospective, Randomized Study of the Effect of Octreotide long-acting repeatable(LAR) in the Control of Tumor Growth in Patients with MetastaticNeuroendocrine Midgut Tumors clinical trial showed that long-acting octreotide significantly prolonged time to tumor progression compared with placebo in patients with functionally active and inactive metastatic midgut NETs; no statistically significant difference in overall survival(OS) was observed, possibly due to the crossover of placebo patients to octreotide. Retrospective observational studies found that long-acting octreotide use was associated with significantly longer OS than no octreotide use for patients with distant metastases although not for those with local/regional disease. CONCLUSION The clinical trial and observational studies with informative evidence support long-acting octreotide's antitumor effect on time to tumor progression and OS. This review showed the rarity of existing studies assessing octreotide's antitumor effect and recommends that future research is warranted.

Prolonged Radiographic Stabilization of a Metastatic Octreotide Scan-Positive Poorly Differentiated Neuroendocrine Tumor Using Octreotide Acetate Therapy Alone

Pancreatic poorly differentiated neuroendocrine tumors (PDNETs) are a subtype of neuroendocrine Tumors (NETs) clinically distinguished by their much more rapid growth and immunohistochemically diagnosed by having a higher Ki-67 cancer cell staining percentage compared to their well or intermediately differentiated NET counterparts. While standard first line treatment for metastatic well or intermediately differentiated pancreatic NETs typically involves octreotide acetate therapy, here I report, to my knowledge, the first case of a patient with a pancreatic PDNET with radiographic stabilization of his disease with octreotide acetate use alone. Octreotide acetate was chosen after first establishing that, based on his octreotide scan, receptors might be targeted using the octreotide analog.

Effect of octreotide combined with carthamin yellow on the blood biochemical indexes of severe acute pancreatitis

Objective:To study the effect of octreotide combined with carthamin yellow on inflammatory cytokines, endocrine hormones and signaling molecules in patients with severe acute pancreatitis.Methods: The patients who were diagnosed with severe acute pancreatitis in our hospitals between June 2014 and October 2017 were selected and randomly divided into the experimental group who accepted octreotide combined with carthamin yellow + conventional symptomatic treatment and the control group who accepted octreotide + conventional symptomatic treatment. Before treatment as well as 5 d and 10 d after treatment, the contents of inflammatory cytokines and endocrine hormones in serum as well as the expression of signaling molecules in peripheral blood were measured.Results: At 5 d and 10 d after treatment, serum TNF-α, ICAM-1, MCP-1, IL-8, sTREM-1, COR, PCT, copeptin, AT-II and ghrelin contents as well as peripheral blood FasL, NOX2, TLR4, TLR9 and p38MAPK expression intensity of both groups were significantly lower than those before treatment, and serum TNF-α, ICAM-1, MCP-1, IL-8, sTREM-1, COR, PCT, copeptin, AT-II and ghrelin contents as well as peripheral blood FasL, NOX2, TLR4, TLR9 and p38MAPK expression intensity of experimental group at 5 d and 10 d after treatment were significantly lower than those of control group.Conclusion: Octreotide combined with carthamin yellow therapy for severe acute pancreatitis can significantly improve the inflammatory response activation and endocrine hormone disorder.

Effects of octreotide combined with gabexate on related cytokines in patients with severe acute pancreatitis

Objective:To study the effects of octreotide combined with gabexate on related cytokines in patients with severe acute pancreatitis (SAP).Methods:A total of 92 patients with SAP from January 2014 to December 2017 in our hospital were enrolled in this study. According to random number table method, the patients were divided into the control group and the treatment group, each groups has 46 patients. The control group were treated with octreotide, the treatment group were treated with octreotide combined with gabexate. To compare the serum B7-H3, PCT, sICAM-1, NF-κB, sTREM-1, BAFF, SAA, NGAL, ghrelin, hs-CRP, MDA and SOD of the two groups before and after treatment.Results: The serum B7-H3, PCT, sICAM-1, NF-κB, sTREM-1, BAFF, SAA, NGAL, ghrelin, hs-CRP, MDA and SOD of the two groups before treatment have no no significantly differences. The serum B7-H3, PCT, sICAM-1, NF-κB, sTREM-1, BAFF, SAA, NGAL, ghrelin, hs-CRP, MDA of the two groups after treatment were significantly lower than before treatment, the serum SOD of the two groups after treatment were significantly better than before treatment, and that of the treatment group were significantly better than the control group after treatment.Conclusion: Octreotide combined with gabexate for patients with SAP can reduce the serum B7-H3, PCT, sICAM-1, NF-κB, sTREM-1, BAFF, SAA, NGAL, ghrelin, hs-CRP, MDA levels, improve serum SOD levels, and it was worthy clinical application.

Effects of ulinastatin combined with octreotide therapy on systemic inflammatory response and intestinal mucosal function in patients with severe pancreatitis

Objective: To investigate the effects of ulinastatin combined with octreotide therapy on systemic inflammatory response and intestinal mucosal function in patients with severe pancreatitis. Methods: A total of 82 patients with severe pancreatitis who were treated in the First People's Hospital of Liangshan Prefecture between March 2015 and August 2017 were reviewed and divided into control group (n=43) and ulinastatin group (n=39), control group received conventional + octreotide therapy, ulinastatin group received conventional +octreotide + ulinastatin therapy, and both groups were treated for 1 week. The differences in systemic inflammatory response and intestinal mucosal function were compared between the two groups before and after treatment. Results: Before treatment, the differences in serum levels of inflammatory mediators and intestinal mucosal function indexes were not statistically significant between the two groups. After 1 week of treatment, serum levels of inflammatory mediators IL-1β, IL-8, HMGB-1 and MCP-1 as well as intestinal mucosal function indexes ET, DAO and D-lactose of ulinastatin group were lower than those of control group. Conclusion: Ulinastatin combined with octreotide therapy on the basis of conventional treatment can further inhibit the systemic inflammatory response and actively protect the intestinal mucosal function in patients with severe pancreatitis.