直肠癌组织中表达内皮抑素与血管生成的关系

目的研究内皮抑素（ES）与直肠癌血管生成的关系,探讨其在直肠癌侵袭行为中的作用。方法应用免疫组织化学方法,检测10例正常直肠组织与40例直肠癌组织中ES蛋白的表达以及微血管密度（MVD）的关系。结果ES阳性评分表达主要在正常直肠黏膜组织,正常黏膜组织的表达高于直肠癌组织[（3．7±0．5）分比（2．6±0．9）分],MVD低于直肠癌组织[（21±4）比（42±7）,P〈0．05]。直肠癌浸润越深,直肠癌组织中Es表达越低[黏膜层（4．0±0．2）分,肌层（3．3±0．2）分,全层（2．4±0．2）分,P〈0．05],MVD逐渐增加[黏膜层（17．5±1．3）、肌层（28．6±2．3）、全层（46．8±3．1）,P〈0．05]。无淋巴结转移的直肠癌组织中ES表达高于有淋巴结转移的直肠癌组织[（3．1±0．2）分比（2．1±0．2）分,P〈0．05],MVD明显低于有淋巴结转移的直肠癌组织中[（30．0±1．5）比（56．2±3．1）,P〈0．05]。随直肠癌浸润深度的增加及淋巴结转移的发生,组织中ES蛋白的表达降低,MVD表达升高（P〈0．05）。结论ES表达降低,肿瘤血管生成增加,MVD升高,可促进直肠癌的局部浸润及淋巴结转移。     

子宫内膜癌组织中内皮抑素VEGF 微血管密度的表达

目的研究内皮抑素、血管内皮生长因子(VEGF)、微血管密度(MVD)在子宫内膜癌中的表达及临床应用价值。方法采用免疫组织化学SP法检测46例子宫内膜癌、34例子宫内膜增殖症和12例正常子宫内膜组织中内皮抑素、VEGF、及MVD的表达情况。结果①内皮抑素在子宫内膜癌组织中的阳性率为80.4%,与在子宫内膜增殖症(29.4%)和正常子宫内膜组织(16.7%)中的阳性表达率差异有统计学意义(P<0.001);②VEGF在子宫内膜癌组织中阳性率为89.1%,与在子宫内膜增殖症(26.5%)与正常子宫内膜(8.3%)中阳性表达率差异有统计学意义(P<0.001);③子宫内膜癌与子宫内膜增殖症、正常子宫内膜之间MVD差异有统计学意义(P<0.001);④内皮抑素和VEGF在子宫内膜癌组织中的表达与临床手术分期相关(P<0.05),MVD与临床手术分期、组织学分级、淋巴结转移和肌层浸润均有关(P<0.001);⑤内皮抑素与VEGF、MVD的表达均有相关性(rs=0.708,P<0.001;rs=0.335,P<0.007),且VEGF与MVD的表达也具有相关性(rs=0.323,P<0.01)。结论内皮抑素、VEGF与子宫内膜癌的发生、发展有关。     

非小细胞肺癌组织中内皮抑素、血管内皮生长因子受体的表达

目的：检测非小细胞肺癌（NSCLC）组织标本中内皮抑素（endostatin）、血管内皮生长因子受体‐2（VEGFR‐2、KDR／FLK‐1）的表达,探讨两者在NSCLC血管新生中的作用及其与临床及病理指标的关系。方法应用免疫组织化学法检测内皮抑素和KDR在28例NSCLC患者癌组织和对照组织中的表达;通过标记CD34的表达情况,计数微血管密度（MVD）。结果肺癌组内皮抑素、KDR表达阳性率分别为60．71％、64．29％,与正常对照组的不表达,差异有统计学意义（P＜0．05）。肺癌组织、对照组织MVD分别为（29．30±3．80）、（98．86±18．87）,差异有统计学意义（P＜0．05）。癌组织中内皮抑素阳性表达的MVD显著低于阴性表达的 MVD ,KDR阳性表达的MVD显著高于其阴性表达的MVD（P＜0．05）。肺癌组织中内皮抑素和KDR有一定的共表达率,内皮抑素和KDR共表达为32．14％,与对照组无共表达比较,差异有统计学意义（P＜0．05）。有淋巴结转移者内皮抑素表达显著低于无淋巴结转移者。结论 NSCLC组织中内皮抑素升高,KDR降低与抑制肿瘤血管新生密切相关。内皮抑素表达与淋巴结转移有关。     

内皮抑素的研究新进展

肿瘤是一种多基因、多因素疾病,它的生长需要多种癌基因和抑癌基因的调节,目前仍是人类死亡的主要原因之一,传统的肿瘤治疗包括手术、化疗、放疗等,主要直接以肿瘤细胞为靶点,存在术后残留肿瘤细胞,药物传递和穿透性问题,及对化疗、放疗不敏感、耐药以及明显的毒副作用和远期治疗效果不佳等问题,因此,研究除手术、化疗、放疗之外的新治疗方法成为医学研究的重点.     

内皮抑素研究进展

内皮抑素是近年发现的血管生成抑制剂 ,具有强大的抑制血管生成作用。此文简要介绍了该药的发现命名、生物学效应、作用机制、药物开发等方面的研究及存在的问题     

血管抑素对口腔鳞癌移植瘤抑制作用的研究

目的:(1)建立口腔鳞状细胞癌裸鼠移植瘤模型。(2)血管抑素(angiostatin)对口腔鳞癌移植瘤抑制作用的研究。方法:建立口腔鳞状细胞癌裸鼠移植瘤模型:将人Tca8113细胞系培养并接种至20只裸小鼠皮下,1周后移植瘤模型建立。再将裸鼠分为一个对照组和3个治疗组,治疗组用3个不同浓度重组人血管抑素干扰。对照组用PBS液注射。每周测量1次肿瘤大小。35天后取标本并称重。结果:rhAGN处理剂量为50mg/(kg·d)、100mg/(kg·d)和200mg/(kg·d)时,肿瘤体积分别为(4945±364)mm3、(2423±258)mm3和(472±48)mm3,与对照组相比,治疗组的体积和重量明显减小(P<0.05,P<0.01);其抑瘤率分别为31.5%、62.0%和85.5%。结论:血管抑素能显著抑制人Tca8113移植瘤的生长,且作用呈剂量依赖性。     

内皮抑素在肿瘤治疗中的研究进展

实体瘤的生长与转移离不开肿瘤血管的生成。当肿瘤生长超过 3ｍｍ3、细胞数达 10 7数量后就必须依赖肿瘤组织中的新生血管形成 (ａｎｇｉｏｇｅｎｅｓｉｓ)来提供生长所必须的养分。如果肿瘤超过这样的体积还缺乏毛细血管和小血管的生成 ,肿瘤将发生退化 ,一旦新生的血管进入肿瘤组织 ,肿瘤则加速生长[1] 。肿瘤血管缺乏周细胞 ,基底膜不完整 ,肿瘤细胞借助肿瘤血管离开原发部位进入血循环 ,易发生浸润和转移。如果抑制肿瘤新生血管的生成 ,肿瘤细胞则因缺血缺氧而部分坏死 ,可抑制肿瘤的生长[2 ] 。因此 ,抑制血管生成可能是抑制肿瘤生长、…     

血管内皮抑素抗肿瘤研究进展综述

内皮抑素作为治疗肿瘤的一种有效手段,近几年来得到一定的发展。本文从内皮抑素的发现及作用机理、内皮抑素的临床试验及应用以及应用中存在的问题、展望等方面对国内外内皮抑素治疗肿瘤的进展进行综述。     

内皮抑素与恶性黑素瘤治疗

<正>黑素瘤是重要的人类恶性肿瘤,占皮肤恶性肿瘤的第三位,占所有恶性肿瘤的1%～2%,且发病率呈上升趋势。随着分子生物学的发展、肿瘤免疫学研究的深入,基因治疗恶性     

重组人内抑素对大鼠佐剂性关节炎继发性炎症的抑制作用

目的　观察重组人内抑素对大鼠佐剂性关节炎 (AA)继发性炎症是否有抑制作用。方法　用足容积测量仪检测足爪容积并对关节炎症程度进行目测评分 ;HE染色检测非致炎侧膝关节的病理改变。结果　福氏完全佐剂 (CFA)致炎后d 1 0 ,继发性炎症出现 ,同时给予不同剂量的内抑素(0 1、0 5、2 5mg·kg- 1 ·d- 1 ,sc) ,连续 7d。结果发现 ,内抑素 2 5mg·kg- 1 对AA大鼠的继发性足肿胀有明显的抑制作用 ;致炎后d 30病理检查显示AA大鼠的关节内滑膜增厚 ,滑膜衬层细胞增生并伴有新生血管形成 ,滑膜细胞有不同程度的脂肪变性 ;软骨及骨遭到破坏 ,且透明软骨内基质降解及新生血管形成。给予不同剂量的内抑素对AA大鼠关节组织的上述病理改变有不同程度的改善作用 ,内抑素 2 5mg·kg- 1 对AA大鼠的关节病理损伤有完全的抑制作用 ,同时可见滑膜组织内大量胶原沉积和滑膜细胞的脂肪变性。结论　重组人内抑素对大鼠佐剂性关节炎的继发性炎症有显著的抑制作用 ,并能阻止关节炎的病理改变     

重组人内抑素对大鼠佐剂性关节炎的影响

目的　观察重组人内抑素对大鼠佐剂性关节炎 (adju vantarthritis,AA)的影响及其作用机制。方法　用福氏完全佐剂 (CFA)诱导大鼠AA模型 ,MTT法检测脾淋巴细胞增殖反应 ,IL 1、IL 2活性的检测采用小鼠胸腺细胞增殖法 ,用放免法检测滑膜细胞培养上清液中IL 1和TNF α水平。结果　CFA致炎后d10 ,AA大鼠出现继发性炎症 ,给予不同剂量的内抑素 0 1、0 5、2 5mg·kg- 1·d- 1,sc ,连续 7d。结果发现 ,内抑素对AA大鼠的继发性足肿胀有抑制作用 ;进一步研究表明内抑素明显抑制AA大鼠过高的ConA诱导的脾细胞增殖反应 ,降低脾细胞IL 2的产生 ;对腹腔巨噬细胞(peritonealmacrophage ,PMΦ)产生过高的IL 1有抑制作用 ;另外 ,内抑素也可明显抑制AA大鼠滑膜细胞产生过高的IL 1和TNF水平。结论　重组人内抑素对AA大鼠具有治疗作用 ,其机制可能与其调节机体异常的免疫有关     

Inhibitory effects of naringenin on tumor growth in human cancer cell lines and sarcoma S-180-implanted mice

We have investigated the effect of naringenin (NGEN) on tumor growth in various human cancer cell lines and sarcoma S-180-implanted mice. NGEN showed cytotoxicity in cell lines derived from cancer of the breast (MCF-7, MDA-MB-231), stomach (KATOIII, MKN-7), liver (HepG2, Hep3B, Huh7), cervix (Hela, Hela-TG), pancreas (PK-1), and colon (Caco-2) as well as leukemia (HL-60, NALM-6, Jurkat, U937). NGEN-induced cytotoxicity was low in Caco-2 and high in leukemia cells compared to other cell lines. NGEN dose-dependently induced apoptosis, with hypodiploid cells detected in both Caco-2 and HL-60 by flow cytometric analysis. In vivo, NGEN inhibited tumor growth in sarcoma S-180-implanted mice, following intraperitoneal or peroral injection once a day for 5 d. Naringin (NG) also inhibited tumor growth by peroral injection but not intraperitoneal injection. NGEN, one of the most abundant flavonoids in citrus fruits, may have a potentially useful inhibitory effect on tumor growth.     

Inhibitory effects of fusarochromanone on melanoma growth

Fusarochromanone is a toxic metabolite produced by Fusarium equiseti, a fungus present in decaying cereal plants in northern latitudes; it has been detected in various food grains. Fusarochromanone has been shown to have both stimulatory and inhibitory effects on various mammalian cells, depending on the concentration used. Whether these cytotoxic effects can be used in the clinical treatment of tumors remains to be established. Here, we evaluated the effects of fusarochromanone on the growth of human melanoma cells both in vitro and in vivo. In vitro, low concentrations (0.1-1 nmol/l) of fusarochromanone were found to be cytotoxic to many melanoma cell lines. In contrast, growth of normal melanocytes was inhibited only at much higher fusarochromanone concentrations (100-200 nmol/l). In vivo, the growth of melanoma cells implanted subcutaneously in immuno-compromised mice was significantly (P<0.05) reduced by daily administration of fusarochromanone. Immunohistological analyses indicated a significant (P<0.05) increase in the expression of active caspase-3 in tumor masses of mice treated with fusarochromanone, compared with controls. Together, these observations show that fusarochromanone increased apoptosis of tumor cells and reduced tumor growth in vivo. Therefore, the effects of fusarochromanone warrant further investigation as an adjuvant molecule to prevent growth and recurrence of melanomas.     

Ad-ING4抑制人A549肺癌细胞及其裸鼠移植瘤的生长

目的 研究腺病毒介导的ING4基因(Ad-ING4)对肺癌体内外的抑制作用及其潜在的分子机制.方法 体外采用50 MOI的Ad-ING4感染A549肺癌细胞,并用MTT法检测Ad-ING4对A549细胞的抑制作用,流式细胞仪检测肿瘤细胞的凋亡率.采用A549细胞株建立人肺癌裸鼠模型,瘤体局部注射干预用药,每隔5天测量一次肿瘤体积,并计算瘤重抑瘤率;瘤块免疫组化检测ING4、生存素(survivin)、CD34、HIF-1等基因的表达.结果 Ad-ING4感染A549细胞抑制率可达47.62%;72 h凋亡率为18.5%;荷瘤裸鼠经治疗后,Ad-ING4组和顺铂(DDP)组的肿瘤体积、瘤重均明显缩小,其抑瘤率分别达到42.43%和46.47%,DDP组出现不良反应;免疫组化检测Ad-ING4组和DDP组与对照组比较,生存素、CD34、HIF-1的表达下调(P<0.01).结论 Ad-ING4对人A549肺癌细胞及其裸鼠移植瘤的生长具有明显的抑制作用.其抑瘤机制可能与下调生存素、CD34、HIF-1的基因表达进而诱导肿瘤细胞凋亡和抑制肿瘤血管形成等有关.     

Inhibitory effects of diet-reduction on monocrotaline intoxication in rats

The effect of diet-reduction on monocrotaline intoxication was studied in male Sprague—Dawley rats. Restriction of the diet (to 8 g/rat/day) inhibited the progression of cardiopulmonary changes resulting from single subcutaneous injections of 60 mg/kg of monocrotaline and significantly prolonged survival.     

蒲黄煎液的抗大鼠实验性血栓作用

目的研究蒲黄对大鼠血栓形成的影响。方法分别采用大鼠动静脉吻合血栓形成模型和电刺激损伤颈总动脉血栓模型实验方法,将SD大鼠随机分为空白对照组、阿司匹林阳性对照组(0.3 g/kg)、蒲黄煎液高剂量组(8 g/kg)、中剂量组(4 g/kg)、低剂量组(2 g/kg),各组动物连续灌胃给药7 d,末次给药后1 h建立模型,测定各组动物血栓湿重及血栓栓塞率;测定血浆凝血酶原时间(PT)、活化部分凝血酶时间(APTT)及凝血酶时间(TT)。结果蒲黄能抑制动静脉吻合血栓的形成,使血栓湿重降低,血栓抑制率达15%~43%;同时蒲黄降低了大鼠电刺激动脉血栓栓塞率,使大鼠APTT、PT、TT明显延长,且具有剂量依赖关系。结论蒲黄能够对抗在体实验性血栓的形成,其抗血栓机制可能与APTT、PT、TT指标的改变有关。     

Inhibitory effects of idoxifene on hepatic fibrosis in rats

AIM: To investigate the effects of a tissue-specific selective estrogen receptor modulator, idoxifene, on hepatic fibrosis in rats. METHODS: Hepatic fibrosis was induced by dimethylnitrosamine (DMN) in male rats. The DMN model of hepatic fibrosis and the hepatocytes undergoing oxidative stress were treated with idoxifene respectively. The effect of idoxifene on hepatic fibrosis in the DMN model was examined by immunohistochemistry. Effects of idoxifene on antioxidant enzyme levels of copper, zinc-dependent superoxide dismutase (CuZn-SOD), and cellular glutathione peroxidase (GSHPx) were measured by ELISA. Effects of idoxifene on activation, proliferation, and apoptosis of culture-activated hepatic stellate cells (HSC) were analysed by immunohistochemistry, bromodeoxyuridine (BrdU) uptake, and flow cytometry, respectively. RESULTS: Idoxifene could markedly suppress DMN-induced hepatic fibrosis in male rats. A treatment of 0.4 mg x kg(-1) x d(-1) of idoxifene reduced the protein levels of collagen in the DMN model by 41.19% (P<0.05). Protein level of CuZn-SOD and activitiy of GSHPx in liver treated with DMN plus 0.4 mg/kg/d of idoxifene were 2.65 times (P<0.05) and 2.08 times greater (P<0.05) than that of liver treated with DMN alone respectively. The protein level of CuZn-SOD and activity of GSHPx in cultured rat hepatocytes treated with ferric nitrilotriacetate (FeNTA) plus 1 multiply 10(-7) mol/L of idoxifene were 3.43 times (P<0.05) and 2.52 times (P<0.05) greater than that treated with FeNTA alone. Idoxifene could inhibit HSC activation. Compared with the control, the uptake of BrdU in HSC cultured with 1 multiply 10(-7) mol/L of idoxifene was reduced by 51.87 % (P<0.05), and the number of apoptotic HSCs cultured with 1 multiply 10(-7) mol/L of idoxifene increased by 94.52% (P<0.05). CONCLUSION: Idoxifene showed inhibitory action on hepatic fibrosis in male rats.     

Inhibitory effects of bromocriptine on corticosterone secretion in male rats

Bromocriptine, a dopamine D2 receptor agonist, is widely used for treating prolactinoma, Parkinson's disease and galactorrhea. However, the influence of bromocriptine on the endocrine system, especially adrenal function, is not clear. The present study was aimed to investigate the effects of bromocriptine on corticosterone production in rats. Male rats were treated or not treated by bromocriptine (5 mg/kg, s.c.) twice per day for 2 days before decapitation. The adrenal zona fasciculata-reticularis cells were prepared and incubated with adrenocorticotropic hormone (ACTH), forskolin (an adenylyl cyclase activator), 8-bromo-adenosine 3':5' cyclic monophosphate (8-Br-cAMP, a membrane-permeable analogue of cAMP), and steroidogenic precursors including 25-OH-cholesterol and pregnenolone. The concentrations of prolactin, corticosterone and pregnenolone in the plasma and/or medium were measured by radioimmunoassay (RIA). The protein expression of cytochrome P450 side-chain cleavage (P450scc) enzyme and steroidogenic acute regulatory protein (StAR) was analyzed by Western blotting. Administration of bromocriptine in vivo resulted in a decrease in the levels of plasma prolactin and corticosterone. Basal-and ACTH-as well as forskolin-stimulated corticosterone secretion by zona fasciculata-reticularis cells was also lower in bromocriptine-treated rats than in control animals. The decreased production of corticosterone in zona fasciculata-reticularis cells could be reversed by administration of 8-Br-cAMP. The corticosterone and pregnenolone release induced by 25-OH-cholesterol in zona fasciculata-reticularis cells was reduced by administration of bromocriptine. The protein expression of both StAR protein and P450scc in zona fasciculata-reticularis cells was inhibited in the bromocriptine-treated group. Administration of bromocriptine in vitro reduced the release of corticosterone stimulated by ACTH and forskolin in rat zona fasciculata-reticularis cells. These results suggested that bromocriptine caused adrenal dysfunction through inhibition of ACTH action and of the activity of adenylyl cyclase, and impaired the early steps of corticosterone biosynthesis.     

Inhibitory effects of different galanin compounds and fragments on osmotically and histamine-induced enhanced vasopressin secretion in rats

The effects of rat, porcine and human galanin, and the human 1-16 and human 16-30 terminal galanin fragments on vasopressin secretion were studied in rat. The plasma vasopressin level was determined by radioimmunoassay (RIA). There were no changes in the basal vasopressin secretion after galanin administration. A significant increase in vasopressin concentration was detected following 2.5% NaCl or histamine administration. I.c.v. injected rat, porcine or human galanin or the 1-16 N-terminal galanin fragment prevented the plasma vasopressin level enhancement. Following the i.v. administration of rat galanin or the i.c.v. injected 16-30 C-terminal galanin fragment, the vasopressin concentration did not return to the normal level. Administration of the galanin antagonist galantid (M15) i.c.v. before the rat galanin i.c.v. injection prevented the inhibitory effect on the increased plasma vasopressin level following 2.5% NaCl solution or histamine administration. The results indicate that there is no significant difference in the inhibitory effect of rat, porcine or human galanin or the 1-16 galanin fragment on the enhanced plasma vasopressin secretion induced by hyperosmosis or histamine administration.Our findings suggest that galanin, as a peptide modulator, is physiologically involved in the regulation of vasopressin release following different forms of stimulation: an osmotic response or histamine administration.