生长抑素受体显像在消化系肿瘤诊断与治疗中的应用

生长抑素受体(SSTR)在多种消化系统肿瘤组织高度表达。生长抑素及其类似物能通过配体与受体的相互作用与SSTR特异性结合,采用放射性核素标记的生长抑素类似物可与靶向肿瘤表面高密度的SSTR结合的特性所开发的生长抑素受体显像(SRS)、生长抑素受体介导放射性核素靶向治疗等技术,对表达SSTR的消化道肿瘤及其转移瘤的诊断及鉴别诊断较其他常规方法敏感性高,特异性强。并能对此类肿瘤进行治疗及监测疗效,故应用前景广阔。     

生长抑素受体显像在消化系肿瘤诊断与治疗中的应用

生长抑素受体(SSTR)在多种消化系统肿瘤组织高度表达。生长抑素及其类似物能通过配体与受体的相互作用与SSTR特异性结合，采用放射性核素标记的生长抑素类似物可与靶向肿瘤表面高密度的SSTR结合的特性所开发的生长抑素受体显像(SRS)、生长抑素受体介导放射性核素靶向治疗等技术，对表达SSTR的消化道肿瘤及其转移瘤的诊断及鉴别诊断较其他常规方法敏感性高，特异性强。并能对此类肿瘤进行治疗及监测疗效，故应用前景广阔。     

生长抑素受体介导的靶向放疗与消化系肿瘤治疗

生长抑素(SST)受体介导的靶向放疗建立在对SST、生长抑素类似物(SSTA)及其受体(SSTR)的研究基础之上。国外对SST及SSTA治疗肿瘤的研究已有多年的历史，而国内研究从2002年开始有大量报道，主要是奥曲肽(octreotide)抗各类肿瘤机制的体内、外实验，以及部分临床试验。目前已经证实SSTA如奥曲肽确有良好的抗肿瘤效应。国外从     

生长抑素对消化系非内分泌肿瘤的治疗作用及机制

生长抑素是一种具有广泛生物学活性的物质 ,近年来生长抑素及其类似物的抗肿瘤作用日渐引起人们的重视 ,并取得一定的疗效。现就生长抑素及生长抑素受体在肿瘤组织中的表达 ,生长抑素及其类似物的抗肿瘤机制以及对胃肠道非内分泌肿瘤的治疗作一综述。     

不同亚型生长抑素受体在消化系肿瘤诊断及治疗中的应用进展

生长抑素受体 (SSTR)是一种G蛋白偶联受体 ,包括 5个亚型 :SSTR1～ 5 ,各亚型通过不同的传导途径发挥抗肿瘤细胞增殖作用。人类消化系统肿瘤组织可表达多种SSTR ,且大多数情况下同时表达两种以上的SSTR ,其中以SSTR2和SSTR5最为常见 ,同一肿瘤不同分期状态下SSTR的表达状态也有所不同。SSTR5′C末端缺失长度与抗细胞增殖作用成正比。临床应用与不同亚型SSTR具有高亲和力的生长抑素类似物有助于某些消化系统肿瘤的诊断与治疗     

不同亚型生长抑素受体在消化系肿肿瘤诊断及治疗中的应用进展

生长抑素受体(SSTR)是一种G蛋白偶联受体，包括5个亚型：SSTRl～5，各亚型通过不同的传导途径发挥抗肿瘤细胞增殖作用。人类消化系统肿瘤组织可表达多种SSTR，且大多数情况下同时表达两种以上的SSTR，其中以SSTR2和SSTR5最为常见，同一肿瘤不同分期状态下SSTR的表达状态也有所不同。SSTR5’C末端缺失长度与抗细胞增殖作用成正比。临床应用与不同亚型SSTR具有高亲和力的生长抑素类似物有助于某些消化系统肿瘤的诊断与治疗。     

生长抑素对消化系非内分泌肿瘤的治疗作用及机制

生长抑素是一种具有广泛生物学活性的物质，近年来生长抑素及其类似物的抗肿瘤作用日渐引起人们的重视，并取得一定的疗效。现就生长抑素及生长抑素受体在肿瘤组织中的表达，生长抑素及其类似物的抗肿瘤机制以及对胃肠道非内分泌肿瘤的治疗作一综述。     

生长抑素类似物的抗肿瘤机制

生长抑素及其类似物对肿瘤的作用越来越引起人们的关注.其抗肿瘤的机制可能为直接抑制肿瘤细胞增殖,拮抗促肿瘤生长的激素或细胞因子,诱导肿瘤细胞凋亡,抑制肿瘤血管生成,增强机体对肿瘤细胞的免疫力等.生长抑素类似物可望在肿瘤治疗方面开辟新的途径.     

生长抑素及其类似物对肝癌及胰腺癌的治疗研究进展

近年发现,生长抑素及其类似物能够抑制肿瘤细胞增殖,诱导肿瘤细胞凋亡,不仅能抑制具有神经内分泌功能肿瘤的增殖,对普通的实体瘤亦有抑制作用,现已初步应用于临床。其生物学活性是通过靶细胞膜上的特异性受体介导,不同组织受体表达量及种类不同,抑瘤效果也不同。肝癌和胰腺癌是消化系统两大恶性肿瘤,对其治疗及防治具有重要意义。     

胰腺癌中生长抑素及其受体的研究现状

胰腺癌早期诊断困难,对化疗、放疗均不敏感。至今尚无理想的治疗措施。近年研究表明,生长抑素具有抗细胞增殖作用,并发现胰腺癌中有许多生长抑素受体亚型表达。生长抑素类似物(somatostatin analogue,SSA)可以抑制胰腺、胃肠激素分泌,阻碍肿瘤细胞生长,并已应用于临床治疗某些肿瘤,如:胰腺癌及其它多种恶性肿瘤,取得了一定的疗效。本文综述生长抑素和受体及其类似物在胰腺癌中的研究进展。     

生长抑素受体1～5与消化系统疾病关系的研究进展

生长抑素受体(SSTR)作为与生长抑素(SST)及其类似物特异性结合的受体在体内广泛分布,尤其是消化系统。SST发挥生理作用需要与其受体结合。SSTR主要有5种亚型(即SSTR1～5),在不同的种属和组织中分布与表达的亚型及量均不同。研究表明,SSTR在相关疾病的诊断与治疗中起重要作用。本文就SSTR各亚型在消化系统疾病中的分布特点及其与相关疾病的关系进行综述。     

Biology of somatostatin in breast cancer

The biological effects of the neuropeptide somatostatin (SST) are mediated via a family of five somatostatin receptors (SSTRs) belonging to a family of G-protein-coupled receptors (GPCRs). SSTR regulate the secretion of hormones, growth factors, neurotransmission and cell growth in receptor-specific manner. In addition, SST plays an inhibitory role in several mammary cancer models. These effects are mediated both indirectly through inhibition of hormones and growth factors which promote tumor growth as well as directly via SSTRs present on tumor cells to inhibit mitogenic signaling of growth factor receptor kinases leading to growth arrest and induction of apoptosis. Here, we present an overview on the role of SST and its analogs in breast cancer.     

Effects of selective somatostatin analogs and cortistatin on cell viability in cultured human non-functioning pituitary adenomas

Clinically "non-functioning" human pituitary adenomas (NFPA) constitute about 35% of pituitary adenomas. Somatostatin receptors (SSTR) expression in these adenomas has previously been described both in vitro and in vivo, without evidence for a correlation with tumor volume or the therapeutic efficacy of somatostatin analogs. This study was performed on 13 surgically removed pituitary macroadenomas, diagnosed before surgery as "non-functioning". In addition, 3 growth hormone (GH)-secreting adenomas served as controls. A specimen from each tumor was dispersed and digested to isolate and culture the tumor cells, and the in vitro effects of SSTR2 and SSTR5 selective analogs and Cortistatin (CST) (100nM) on cell viability were studied. The quantity of viable cells was estimated using the XTT method. RNA purification of tumor samples and subsequent RT-PCR studies for SSTR2 and SSTR5 expression were performed. Somatostatin analog with high affinity for SSTR2 reduced cell viability by 20-80% in 8 of 13 NFPAs studied, all expressing the SSTR2. The inhibitory effect on cell viability of SSTR5-selective analog was 15-80% in 10 of 13 NFPAs studied, all but three expressing the SSTR5. CST, however, effectively reduced cell viability in only 6 NFPAs. Cell viability was inhibited by all peptides studied in 2 out of 3 GH-secreting adenomas, expressing both receptors. The third adenoma responded to SSTR2 analog and expressed only SSTR2. These results suggest the involvement of SSTR2 and SSTR5 in the anti-proliferative effects of somatostatin; however, CST is less potent in reducing cell viability in these tumors.     

生长抑素对Oddi括约肌功能的影响

天然生长抑素(somatostatin,SST)是一种胃肠激素及神经肽,主要分布于神经和消化系统中,具有广泛的生物学效应. 消化系SST大多由胰腺和胃肠黏膜中的D细胞分泌,能抑制胃肠运动及多种激素分泌. SST调节作用由G蛋白偶联受体,即生长抑素受体(somatostatin receptor,SSTR)介导. Oddi括约肌(sphincter of Oddi,SO)位于十二指肠乳头周围,是一结构和功能相对独立的器官,其运动主要受神经、激素、Cajal间质细胞的调节. SST对SO的作用尚存在争议,本文就生长抑素对SO功能的影响进行综述.     

Comparative analyses of sequence structure,evolution, and expression of four somatostatin receptors in orange-spotted grouper (Epinephelus coioides)

Somatostatins (SSs) and somatostatin receptors (SSTRs) play important roles in the growth, development and metabolism of vertebrates. In the present study, four SSTRs were isolated from orange-spotted grouper (Epinephelus coioides), a coral fish of high commercial value cultivated in Southeast Asia. Phylogenetic tree analysis grouped the four SSTRs as two distinct groups of SSTR1 and SSTR2/3/5. Four SSTRs exhibited high homology across the vertebrates. The expression of four grouper SSTR mRNAs was studied in 11 tissues. The highest level of SSTR1 mRNA was found in forebrain. The mRNAs of SSTR2 and SSTR3 were highly expressed in pituitary, forebrain and liver. The levels of SSTR5 mRNA were low in most tissues except for pituitary and intestine. The expression of four grouper SSTR mRNAs was investigated in seven embryonic stages and five early larval development stages. The highest levels of SSTR1 and 2 mRNAs appeared during hatching, while the highest levels of SSTR3 and 5 mRNAs were found in brain vesicle stage. Intraperitoneal injection of SS14 significantly increased the levels of all four SSTR mRNAs in pituitary and SSTR1, 3 mRNAs in liver in a dose-dependent manner, but no effect on SSTR2 and 5 in liver. These observations contribute to the understanding of the evolution of SSTR family and offer information on structure, distribution and function of fish SSTRs.     

Relationship between somatostatin receptor subtype expression and clinicopathology, Ki-67, Bcl-2 and p53 in colorectal cancer

AIM: To study the SSTR1, 2, 3, 4, 5 expression and their relationships with clinico-pathological factors, cell proliferation, Bcl-2 and p53 expression in colorectal cancer cells. METHODS: Immunohistochemical staining of five SSTR subtypes, Ki-67, Bcl-2 and p53 was performed by the standard streptavidin-peroxidase (SP) technique for the paraffin sections of 127 colorectal cancers, and expression of five SSTR subtypes in 40 specimens of normal colorectal mucosae was detected with the same method. RESULTS: Positive staining for five SSTR subtypes was observed in colorectal cancer cells and normal colorectal mucosae. SSTR1 was the most predominant subtype in both colorectal cancer and normal colorectal mucosa, and the second was SSTR5 or SSTR2. As compared with normal colorectal mucosa, SSTR4 was more frequently expressed in colorectal cancer cells (2.5% vs 18.9%, P< 0.05); the expression of SSTR2, 4, 5 in moderately to well differentiated colorectal adenocarcinoma was significantly higher than that in poorly differentiated ones (P< 0.05), the SSTR1 expression in colorectal cancer with positive lymph node metastasis was significantly higher than that with negative lymph node metastasis (72.2% and 54.5%, P< 0.05). In addition, in the ulcerative type of colorectal cancer, SSTR2 expression was obviously decreased (P < 0.05); the correlation did not reach a statistical significance between the five SSTR subtypes expression and Dukes'stages (P> 0.05), but the frequency of SSTR1 expression increased with Dukes' stage, while SSTR3 and SSTR5 expression decreased with Dukes' stage. Moreover, there was no correlation between expression of the five SSTR subtypes and other clinicopathological factors such as age, sex, tumor site, tumor depth, distant metastasis. The proliferative indexes in colorectal cancer cells with negative expression of SSTR2 and SSTR3 were significantly higher than that with positive expression (P<0.05). The Bcl-2 expression in colorectal cancer cells with positive expression of SSTRl, 2, 3, 5 was significantly lower than that with negative expression (P<0.05). There was no correlation between five SSTR subtypes and p53 expression. CONCLUSION: The most predominant SSTR subtype is SSTR1, and the second is SSTR2 or SSTR5. Five SSTR subtypes play different roles in the development of colorectal cancer. SSTR2 and SSTR3 can inhibit the proliferation and promote apoptosis of tumor cells.     

Gene transfer of somatostatin receptor type 2 by intratumoral injection inhibits established pancreatic carcinoma xenografts

AIM: To investigate the therapeutic effect of somatostatin receptor type 2 (SSTR2) gene transfection on pancreatic carcinoma xenografts in vivo in experimental cancers. METHODS: Human pancreatic cancer cell line Panc-1 was inoculated subcutaneously into the back of nude mice. When tumor nodules were grown as large as about 5 mmx5 mm days after inoculation, the mice were randomly divided into 3 groups (6 mice in each group). Group Ⅰ served as untreated control group. Group Ⅱ received an intratumoral injection of a combination of human cytomegalovirus promoter-6C (pCMV-6C) and lipofectamine 2000. Group Ⅲ received an intratumoral injection of a combination of pCMV-6C-SSTR2 and lipofectamine 2000. The rate of tumor growth was compared among these three groups. The expression of SSTR2 in these tumors was detected by immunohistochemistry and Western-blot. Apoptosis index (AI) in these tumors was examined by using TUNEL in situ. RESULTS: Intratumoral injection of a combination of pCMV-6C-SSTR2 and lipofectamine 2000 resulted in the expression of SSTR2 protein. The tumor size and weight in group Ⅲ (0.318±0.098 cm3, and 0.523±0.090 g, respectively) were significantly lower than those in group I (2.058±0.176 cms, and 1.412±0.146 g, respectively) and group Ⅱ (2.025±0.163 cm3, and 1.365±0.116 g, respectively) (P<0.05) The AI in group Ⅲ (1.47±0.13%) was significantly higher than that in groupⅠ(0.56±0.09%) and group Ⅱ (0.57±0.11%) (P<0.05). But there were no significant differences between groups Ⅰ and Ⅱ. CONCLUSION: Our data demonstrate that re-expression of SSTR2 gene has antitumor effects on experimental pancreatic cancer. Restoration of SSTR2 gene expression through gene transfer in vivo might be a potential gene therapy strategy for human pancreatic cancer.     

Regression of liver metastases of occult carcinoid tumor with slow release lanreotide therapy

Few clinical studies have demonstrated an anti-proliferative activity of somatostatin (SST) analogs in carcinoids. We report the case of a woman with liver metastases of neuroendocrine tumor and no evidence of the primary tumor. The liver metastases were characterized by high proliferation index, immunoreactiviy for somatostatin receptor (SSTR)-l, 2, 3 and 5 and positive octreoscan. Urinary 5-hydroxyindolacetic acid, serum serotonin and chromogranin A were elevated. Slow release lanreotide (SR-LAN) therapy for 3 mo controlled clinical and biochemical signs of carcinoid tumor and caused a clear-cut reduction in the diameter of two liver metastases and disappearance of another lesion, with further reduction after 6 and 18 mo. We demonstrated a clear-cut long-lasting anti-proliferative effect of SR-LAN on liver metastases of occult carcinoid with high proliferation index and immunoreactivity for SSTR-1, 2, 3, and 5. Immunohistochemistry for SSTRs could be a suitable method for the selection of patients with metastatic carcinoid that may benefit from SST analog therapy.     

SSTR1和SSTR2在肠易激综合征和活动期溃疡性结肠炎患者结肠黏膜中的表达及其临床意义

生长抑素是胃肠道重要神经递质之一,其功能的发挥是由生长抑素受体（SSTR）介导的,SSTR表达水平与多种胃肠道疾病有关。目的：研究SSTR1、SSTR2在肠易激综合征（IBS）和活动期溃疡性结肠炎（UC）患者结肠黏膜中的表达及其临床意义。方法：收集腹泻型IBS（IBS—D）、便秘型IBS（IBS—C）、活动期UC患者和正常对照者各30例,记录患者的症状发生时间、严重程度并评分。以免疫组化方法检测活检结肠黏膜中SSTR1、SSTR2的表达。结果：SSTR1、SSTR2的表达位于上皮组织的上皮细胞和间质淋巴细胞的细胞膜和细胞核中。正常结肠黏膜组织中两者均为弱阳性表达,IBS组和UC组SSTR2表达阳性率和免疫组化评分显著高于正常对照组（P〈0．05）。各组中SSTR1、SSTR2免疫组化评分均呈线性正相关（P〈0．05）。SSTR1、SSTR2的表达与IBS—D的腹泻病程和程度以及UC的便血程度相关（P〈0．05）,SSTR2的表达与IBS-C的便秘病程和程度相关（P〈0．05）。结论：SSTR1、SSTR2在正常结肠黏膜中为弱阳性表达．两者在IBS和UC的发病中起有一定作用。UC与IBS—D在发病机制上可能存在一定关联。