一氧化氮与肿瘤转移

一氧化氮(NO)的生物学活性广泛,多种肿瘤组织存在一氧化氮合成酶(NOS)表达异常和(或)NO产生异常.宿主和肿瘤细胞的NOS表达及NO合成差异,对肿瘤细胞的生存和转移潜能有不同影响.研究NO及NOS在肿瘤细胞转移过程中的效应机制,有望发现防治肿瘤转移的潜在靶点.     

骨桥蛋白及诱导型一氧化氮合成酶在胃癌中的表达

目的　研究骨桥蛋白在胃癌组织中的表达及其与诱导型一氧化氮合成酶表达的关系。方法　应用免疫组织化学方法检测胃癌组织中骨桥蛋白和诱导型一氧化氮合成酶的表达 ,并进行随访。结果　 66例胃癌组织中骨桥蛋白和诱导型一氧化氮合成酶表达的阳性率分别为 72 .7% ( 4 8/66)、75 .7% ( 5 0 /66) ,骨桥蛋白的表达与肿瘤浸润深度、肿瘤直径、淋巴结转移程度及有无远处转移有关 ,iNOS的表达与肿瘤浸润深度、肿瘤直径、淋巴结转移程度有关。结论　骨桥蛋白在胃癌组织中表达均增强 ,能够作为反映肿瘤的生物学特性 ,评估预后的重要参考指标。骨桥蛋白和iNOS表达有协同作用。     

一氧化氮在肿瘤治疗中的研究进展

一氧化氮是一种人体内广泛存在的气体信号分子,在肿瘤细胞中,可根据其浓度高低发挥抗瘤和促瘤双重作用。基于这种特性,高浓度一氧化氮被认为是一种新的肿瘤治疗方式,称为一氧化氮气体疗法。在肿瘤微环境中,一氧化氮气体不仅自身发挥抗瘤作用,还可以生成具有更强氧化性的活性氮,共同介导DNA损伤、诱导线粒体功能障碍,调控细胞因子导致细胞死亡。一氧化氮气体疗法可以与多种肿瘤治疗方式协同,实现增加药物累积,控制气体释放,抑制肿瘤侵袭和转移等效果,进而提高疗效。这篇综述主要从介导遗传毒性和诱导凋亡效应两方面讨论一氧化氮的抗肿瘤作用以及一氧化氮气体疗法在肿瘤联合治疗中的应用。     

癌症患者血NOS、NO水平变化及临床意义

目的探讨恶性肿瘤患者血一氧化氮合成酶(NOS)和一氧化氮(NO)的水平变化及其临床意义.方法测定106例肿瘤患者和50例健康人血的NOS、NO水平,进行统计学分析,比较它们之间的差异.结果肿瘤患者的NOS、NO水平明显高于健康人(P＜0.01)、未手术切除者NO比手术切除者高(P＜0.05).结论 NO与肿瘤的发生、发展有密切的关系,检测NOS、NO的水平,可作为肿瘤诊断以及判断病情变化和预后的指标之一.     

肿瘤患者血清一氧化氮(NO)水平

一氧化氮(ｎｉｔｒｉｅｏｘｉｄｅＮＯ)是一种小分子物质,在生物体内作为重要的信使分子和效应分子是在80年代的后期才被发现与证实。一氧化氮(ＮＯ)在体内参与众多的生理病理过程,作用极为广泛。随着研究的深入,一氧化氮(ＮＯ)与肿瘤的生物学关系亦受到关注。研究表明诱导肿瘤中产生高浓度的一氧化氮(ＮＯ),可以增加对瘤细胞的杀伤作用。为此,我们检测了肿瘤患者的血清,以了解肿瘤病人一氧化氮(ＮＯ)水平。病例来源:53例肿瘤病人均为我院肿瘤放疗科初治病例,男30例,女23例,其中食道及胃部肿瘤34例,肺癌10例,肠癌6例,乳腺癌1例,神经胶质瘤2…     

骨桥蛋白及诱导型一氧化氮合成酶在胃癌中的表达

目的 研究骨桥蛋白在胃癌组织中的表达及其与诱导型一氧化氮合成酶表达的关系。方法 应用免疫组织化学方法检测胃癌组织中骨桥蛋白和诱导型一氧化氮合成酶的表达，并进行随访。结果 66例胃癌组织中骨桥蛋白和诱导型一氧化氮合成酶表达的阳性率分别为72．7％(48／66)、75．7％(50／66)，骨桥蛋白的表达与肿瘤浸润深度、肿瘤直径、淋巴结转移程度及有无远处转移有关，iNOS的表达与肿瘤浸润深度、肿瘤直径、淋巴结转移程度有关。结论 骨桥蛋白在胃癌组织中表达均增强，能够作为反映肿瘤的生物学特性，评估预后的重要参考指标。骨桥蛋白和iNOS表达有协同作用。     

一氧化氮与肿瘤转移

一氧化氮(NO)的生物学活性广泛，多种肿瘤组织存在一氧化氮合成酶(NOS)表达异常和(或)NO产生异常。宿主和肿瘤细胞的NOS表达及NO合成差异，对肿瘤细胞的生存和转移潜能有不同影响。研究NO及NOS在肿瘤细胞转移过程中的效应机制，有望发现防治肿瘤转移的潜在靶点。     

化疗对多发性骨髓瘤血清一氧化氮、一氧化氮合成酶影响的探讨

近年来,人们发现一氧化氮(NO)、一氧化氮合成酶(NOS)不仅在细胞间信息传递及免疫功能调节方面有重要作用,而且在肿瘤所致的免疫抑制方面也有重要意义.为探讨化疗对多发性骨髓瘤患者血清NO、NOS的影响,我们对10例MM患者于化疗前及第1次至第4次化疗后,分别测定NO、NOS,现将结果报告如下.     

一氧化氮的产生与肿瘤血管形成

一氧化氮是最小及最简单的生物合成产物，可调节人体一系列的生理功能及病理过程。本文综述了一氧化氮的产生在肿瘤血管形成中所起的作用及其临床应用前景。     

VEGF, b-FGF,NOS2 和 NOS3在非小细胞肺癌的表达及其临床意义

目的 :研究血管内皮生长因子 (VEGF)、碱性成纤维细胞生长因子 (b -FGF)、一氧化氮合酶 2 (诱生型 ,NOS2 )、一氧化氮合酶 3(内皮型 ,NOS3)在非小细胞肺癌 (NSCLC)中的表达及其与肿瘤血管形成和淋巴结转移的关系。方法 :用免疫组化 (S -P法 )染色技术对 95例NSCLC石腊组织标本的VEGF、b -FGF、NOS2 和NOS3及肿瘤内微血管密度 (IMVD)进行检测和分析。结果 :VEGF、b FGF表达与TNM分期、IMVD及淋巴结转移有关 (P<0 .0 5) ,两者共表达与IMVD有关 (P <0 .0 1 )。NOS3与组织学分型、IMVD和淋巴结转移有关 (P <0 .0 5) ;NOS2与IMVD有关 (P <0 .0 5)。相关分析显示促血管形成因子 (VEGF、b FGF)与一氧化氮合酶 (NOS2 、NOS3)的表达呈正相关 (r=0 .30 1 8,P <0 .0 5)。结论 :VEGF和b FGF在促进血管形成和促进肿瘤转移方面可能起到协同作用 ,并且有NO的参与 ;VEGF、b FGF、NOS2 和NOS3的检测对于判断NSCLC转移和预后及具有临床应用价值     

一氧化氮/一氧化氮合酶信号系统与前列腺癌

一氧化氮(NO)作为体内重要的信使分子,其生物学作用复杂、多样,与一氧化氮合酶(NOS)活性及表达密切相关.NO通过G蛋白受体激活的信号转导途径参与肿瘤细胞增殖、迁移和血管新生,与前列腺癌的发生、发展密切相关.NO供体药物及NOS抑制剂具有抗肿瘤和放化疗增敏的作用.     

内皮型一氧化氮合酶来源的NO调节肿瘤血管的生成

背景与目的:内皮型一氧化氮合酶(endothelial nitric oxide synthase,eNOS)来源的一氧化氮(nitric oxicle,NO)广泛表达于肿瘤组织,调节着肿瘤血管的生长,但研究结果并不一致。本研究中探讨NO对肿瘤血管形成的作用及其机制。方法:将C57BL/6小鼠随机分为3组:NO组小鼠右胁下接种eNOS基因转染的Lewis肺癌细胞;eNOS拮抗组小鼠接种Lewis肺癌细胞后腹腔注射eNOS拮抗剂L-NAME;对照组接种Lewis肺癌细胞后注射同等体积的生理盐水。处理3周后,测定血浆内NO含量,计数外周血中内皮祖细胞(EPC)数;取肿瘤组织测定每高倍视野下(HPF)血管密度、EPC细胞数量和血管内皮细胞生长因子及其受体复合物(VEGF-VEGFR)的表达。结果:接种Lewis细胞4周后,对照组肿瘤体积为(3022±401)mm3,而L-NAME组和eNOS组分别为(1204±97)mm3和(1824±239)mm3,三组比较有显著性差异(P<0.01)。eNOS基因转染组肿瘤组织内eNOS蛋白表达和NO的生成显著高于对照组,但肿瘤组织中EPC数量[(48±19)/HPF]、血管密...     

Overexpressed beta-catenin blocks nitric oxide-induced apoptosis in colonic cancer cells

Beta-catenin plays an important role in colonic tumorigenesis whereas inducible nitric oxide synthase and nitric oxide are elevated in colonic inflammation. Resistance of colonic epithelial cells to the induction of apoptosis may contribute to tumor development. Nitric oxide can stimulate apoptosis and, paradoxically, is implicated in the development of colon cancer. Our hypothesis was that beta-catenin could increase the resistance of colonic cancer cells to nitric oxide-induced apoptotic cell death. Here we show, using a beta-catenin overexpression system, that increased cytosolic beta-catenin renders colonic epithelial cells more resistant to nitric oxide-induced apoptotic cell death, independently of nitric oxide-induced accumulation of p53. Furthermore, we show that this occurs through inhibition of nitric oxide-induced release of cytochrome c from mitochondria and by blocking both the nitric oxide-induced suppression of the antiapoptotic protein, Bcl-xL, and the phosphorylation of Akt. We contend that increased nitric oxide production, such as that which occurs in chronic colonic inflammation, may select the cells with oncogenic mutant beta-catenin regulatory genes and contribute to human colonic carcinogenesis and tumor progression.     

胃癌组织和血清一氧化氮及一氧化氮合成酶定量分析

目的：探讨一氧化氮（ＮＯ）与胃癌的关系。方法：应用比色法测定了３１例胃癌患者血清和组织的ＮＯ及一氧化氮合成酶（ＮＯＳ）含量，并设２５例正常人和２６例胃十二批肠溃疡为血清对照组。结果：胃癌患者血清ＮＯ水平明显低于正常对照组及胃十二指肠溃疡组（Ｐ〈０．０１）；而溃疡组则明显高于正常对照组（Ｐ〈０．０５）；胃癌组织中ＮＯ及ＮＯＳ含量则高于癌旁组织（Ｐ〈０．０５）。结论：当胃癌发生时，巨噬细胞产大大量的Ｎ     

Phagocytic activity and nitric oxide production of circulating polymorphonuclear leukocytes from patients with peritoneal carcinomatosis

Many studies have demonstrated an increase of neutrophils in patients with advanced cancer. However, the possible role of increased neutrophils in various neoplasms studied to date varies considerably. The authors examined the changes in white blood cell counts in patients with peritoneal carcinomatosis. Malonildialdehyde and nitric oxide (NO) plasma and ascitic fluid levels, phagocitic activity and the ability of the polymorphonuclear cells (PMNCs) to produce nitric oxide were also measured. An increase in PMNCs and decrease in lymphocytes was found in cancer patients. Compared with healthy controls, cancer PMNCs showed significant enhancement of phagocytosis. Similarly, pretreatment of healthy PMNCs with crude supernatants from short-term cultures of the peritoneal cells from ascitic fluid of patients with peritoneal carcinomatosis caused marked stimulation of PMNC phagocytosis. In addition, plasma and ascitic fluid nitric oxide levels in cancer patients were significantly higher than those found in control one. Most importantly, it was found that PMNCs from cancer patients release significantly more nitric oxide than corresponding normal controls. Therefore, considering the fact that neutrophils make up more than 50% of total leukocytes, these cells can play one of the most important roles in tumor biology.     

Oxidative stress contributes to the anti-proliferative effects of flavone acetic acid on endothelial cells

The synthetic flavonoid flavone acetic acid (FAA) has anti-tumor activity against a variety of transplanted tumors in mice through mechanisms which likely involve effects on tumor vasculature and the host immune system. The aims of the present in vitro study were to compare the sensitivity of tumor and endothelial cells to FAA treatment and to assess if nitric oxide and superoxide are involved in the FAA-mediated suppression of cell proliferation. FAA at 1 mM concentration was approximately two times more effective in suppressing proliferation of endothelial than tumor cells. The anti-proliferative effect of 1 mM FAA on endothelial cells was partially blocked by inhibitors to various superoxide-producing enzymes (xanthine oxidase, cyclooxygenase, poly-ADP-ribose polymerase, ribonucleotide reductase) and completely inhibited by the direct scavengers of superoxide lucigenin and Tiron. In contrast, inhibitors of nitric oxide were unable to prevent the effects of FAA on proliferation. FAA induced apoptosis of endothelial cells, which was not affected by inhibitors of nitric oxide or superoxide. Our data imply that FAA inhibits proliferation of endothelial cells by a superoxide-dependent mechanism and induces apoptosis by a nitric oxide and superoxide-independent mechanism.     

Expression of inducible nitric oxide synthase and cyclooxygenase-2 in angiogenesis and clinical outcome of human gastric cancer

BACKGROUND AND OBJECTIVES: It has been recognized that inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) produce important endogenous factors of human tumors such as nitric oxide (NO) and prostaglandins, which is involved in the process of carcinogenesis and tumor progression. This study aimed to evaluate the association of clinicopathologic factors, microvessel density, and patient survival with the expression of iNOS and COX-2 in patients with gastric adenocarcinoma. MATERIALS AND METHODS: Seventy-nine specimens, resected from patients with gastric adenocarcinoma, were investigated by immunohistochemical stain against iNOS and COX-2. Microvessels were stained using anti-CD34 antibody and counted as microvessel density. RESULTS: Positive iNOS and COX-2 expressions were significantly correlated with microvessel density by multivariate analysis, respectively (P = 0.0127 vs. P = 0.0214). There was significant difference among the four groups (both iNOS and COX-2 positive, iNOS positive only, COX-2 positive only, and both negative) in serosal invasion (P = 0.038), lymph node metastasis (P = 0.038), Helicobacter pylori infection (P = 0.025), vascular invasion (P = 0.035), and microvessel density (P = 0.019). In patients with gastric cancer that co-expressed iNOS and COX-2, prognosis was significantly poorer than in those that expressed either iNOS or COX-2, or did not express both of them (P = 0.01738). The Cox proportional hazard regression analysis indicated that iNOS expression, vascular invasion, serosal invasion, and microvessel density are independent prognostic factors for patients with gastric cancer. CONCLUSIONS: iNOS and COX-2 expression of gastric cancer are related to tumor angiogenesis, tumor progression, and patient survival in human gastric cancer.     

卵巢肿瘤一氧化氮合酶的活性研究

目的　探讨一氧化氮合酶 (nitricoxidesynthase ,NOS)与卵巢肿瘤间的关系 ,并观察其在卵巢肿瘤组织中的分布。方法　NOS的比活性用分光光度法 ,NOS在组织中的分布用NADPH 黄递酶组化染色法。结果　 (1)卵巢恶性肿瘤组织中NOS活性较正常卵巢组织和卵巢良性肿瘤组织显著增高 (P <0 0 1)。 (2 )卵巢良性肿瘤和正常卵巢组织中NOS含量差异无显著性 (P >0 0 5 )。 (3)NOS活性随卵巢恶性肿瘤组织分化程度降低而增高 (P <0 0 1)。 (4)恶性肿瘤患者血清中NOS活性高于正常对照。 (5 )在卵巢恶性肿瘤组织中NADPH 黄递酶染色呈阳性 ,而间质呈阴性 ;癌组织中染色深度高于正常卵巢及卵巢良性肿瘤组织 (P <0 0 1)。 (6 )NOS主要分布于癌细胞的胞膜和胞浆 ,胞核基本不着色。结论　一氧化氮 (nitricoxide,NO)合成的增多 ,可能与卵巢恶性肿瘤生长及恶性行为有关 ,卵巢恶性肿瘤组织中NOS含量增高是NO合成增多的重要原因之一。     

Ovariectomy aggravates hypersensitivity reactions to paclitaxel in rats

The incidence of hypersensitivity reactions is still a matter of serious concern during chemotherapy with paclitaxel, particularly in patients with ovarian cancer. We recently reported that intravenous injection of paclitaxel causes acute lung injury characterized by vascular hyperpermeability, edema and respiratory dysfunction in rats. In the present study, we investigated the influence of ovariectomy on the paclitaxel-induced acute lung injury in rats. Ovariectomy worsened paclitaxel-induced acute lung injury, which was reversed by 17beta-estradiol. The mRNA expression for endothelial nitric oxide synthase was reduced in lungs of ovariectomized rats. To determine the role for nitric oxide, we examined the effects of several agents that modulate nitric oxide concentration on the pulmonary response to paclitaxel. In ovary-intact rats, a nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester exaggerated paclitaxel-induced acute lung injury, while nitric oxide donors such as sodium nitroprusside and isosorbide dinitrate attenuated the lung injury. Sodium nitroprusside was also effective in alleviating the paclitaxel-induced acute lung injury in ovariectomized rats. These findings suggest that ovariectomy enhances the susceptibility to paclitaxel hypersensitivity, in which decrease in estrogen and subsequent reduction in nitric oxide synthesis may be involved.