Association with nitric oxide synthase expression, p53 alteration and TGF β signal-transduction abnormality in human tumors

一氧化氮(NO)是一种自由基气体，与细胞生物学中的许多事件有关，包括血管生成、神经传递和细胞毒性。诱导型一氧化氮合酶在多种类型的癌中均有频繁表达。INOS的免疫反应性也提示iNOS可能在肿瘤的行为中发挥重要作用。应用免疫组织化学方法检测iNOS在尿路上皮癌、食道癌、肺癌和肾癌中的表达，以确定iNOS在肿瘤行为中的意义。未发现iNOS免疫染色阴性的尿路上皮癌。105例肿瘤中，55例食管癌iNOS抗体阳性。80%以上的肺癌组织中iNOS免疫反应阳性。未发现诱导型一氧化氮合酶免疫反应与任何临床病理因素以及P53免疫反应之间的显著关联。人们普遍认为，P53基因突变起着关键的…作用在人类癌症的发生过程中有更多的OLE。少量的体内研究表明，P53基因突变与诱导型一氧化氮合酶(INOS)在人类软骨病中的存在有很强的正相关关系，提示内源性NO过量直接导致P53基因突变。通过对肾癌患者的基因组DNA进行VHL基因分析，以确定突变的基因类型及其参与诱导型一氧化氮合酶或p53表达的频率。在17例VLH型突变的肾癌中，15例(88.3%)呈胞浆免疫染色，其中5例为同质性，10例为异质性。在9例无VHL突变的肾癌中，4例(44.4%)呈胞浆免疫染色，其中2例为同质性，2例为异质性。未发现肾癌中P53的过度表达与iNOS免疫反应或VHL改变之间的关系。这些发现为VHL突变的肾癌中iNOS蛋白的频繁表达提供了证据。较少

Nitric oxide (NO) is free radical gas which is associated with several events in cell biology, including angiogenesis, neural transmission and cytotoxicity. Frequent iNOS expressions have been observed in many types of carcinomas. Immunoreactivity of iNOS has also suggested that iNOS might play an important role in the behavior of tumors. We immunohistochemically examined the expression of iNOS in patients with urothelial cancer, esophageal cancer, lung cancer and renal cancer to determine the significance for the tumor behavior. No urothelial cancers exhibited negative iNOS immunostaining were found. Of 105 tumors, fifty-five esophageal cancers were positive with anti-iNOS antibody. Positive immunoreaction of iNOS was also found more than 80% of lung cancers. No significant association between iNOS immunoreactivity and any clinicopathological factors as well as p53 immunoreactivity were found in each human cancer examined.It is accepted that mutation of the p53 gene plays a critical r … More ole in the process of the carcinogenesis of human cancer. Small numbers of in vivo studies have revealed that there was strong positive relationship between p53 gene mutation and the presence of iNOS in human malinancy, suggesting that an excess of endogenously formed NO directly generates a p53 gene mutation. We present here that there was significant relationship between p53 alterations not in urothelial cancers but in esophageal cancers.Genomic DNA from the RCC patients was examined by VHL gene analysis to characterize the genotype of alterations and their frequency of involvement in iNOS or p53 expression. Of 17 RCCs with VLH mutations, fifteen tumors (88.3%) exhibited cytoplasmic immunostaining, including five homogenous and ten heterogeneous. Of 9 RCCs without VHL mutations, four tumors (44.4%) exhibited cytoplasmic immunostaining, including two homogenous and two heterogeneous. No association between p53 overexpression and iNOS immunoreactivity or VHL alteration in RCCs examined were found. These findings provide evidence for frequent iNOS protein expression in RCCs with VHL mutations. Less