nm23—H2mRNA表达与肾母细胞瘤临床行为的关系

应用Ｎｏｒｔｈｅｒｎｂｌｏｔ分子杂交技术，检测３０例肾母细胞瘤及其对应正常肾组织中ｎｍ２３－Ｈ１ｍＲＮＡ表达。通过ｎｍ２３－ｈ１ｍＲＮＡ水平的比较及其与临床病理的分析，发现肾母细胞瘤ｎｍ２３－Ｈ１ｎＲＮＡ呈低表达，随着病程的演进和转移的出现，肿瘤细胞中ｎｍ２３－Ｈ１ｎＲＮＡ表达水平呈显著性降低与肿瘤的病理类型无显著相关性。提示ｎｍ２３－Ｈ１ｎＲＮＡ低表达可能是肾母细胞瘤演和转移的重要因素。     

肾癌组织中CD44V6和nm23-H1蛋白表达及其临床意义

目的 探讨评估肾细胞癌预后因素的指标。方法 应用原位杂交技术检测60例肾癌组织中CD44V6 mRNA和nm23-H1 mRNA表达情况。结果 肾癌组织中CD44V6 mNRA和nm23-H1 mRNA表达阳性率分别为71．7％和56．7％。肾细胞癌的病理分级、临床分期和淋巴结转移与CD44V6 mRNA高表达和nm23-H1 mRNA低表达有关（P＜0．05）。CD44V6 mRNA表达与nm23-H1 mRNA表达呈负相关性（P＜0．05，γ=-0.42)。结论 CD44V6 mRNA高表达和nm23-H1 mRNA低表达对判断肾细胞癌分化程度、预测淋巴结转移有一定的参考价值。     

胆管癌细胞中nm23-H1蛋白的表达及临床意义

目的：探讨人胆管癌细胞中nm23－H1的表达水平与胆管癌转移的关系。方法：应用S－P免疫组化法对52例人胆管癌细胞中nm23－H1的表达水平进行研究。结果：nm23－H1低表达者淋巴结转移率（60．0％）高于正常表达者（19．0％，P＜ 0．05），并且nm23－H1基因的表达水平和胆管癌组织学类型、分化程度存在明显相关（P＜ 0．05）。结论：nm23－H1的低表达在胆管癌的淋巴转移中起重要作用。     

肾母细胞瘤动物模型相关基因和临床研究

肾母细胞瘤动物模型相关基因和临床研究是在历年临床治疗的经验和资料的基础上，应用组织病理学、免疫组织化学、原位杂交、聚合酶链反应（PCR）等现代技术，对肾母细胞瘤的亚型组织结构、WTI、p53基因缺失和突变，微卫星不稳定性（MSI），IGF－D和＂m23－H；基因mRNA表达进行了系统研究。并采用化学致癌物质诱导建立大鼠肾母细胞瘤模型，结合临床治疗和预后因素分析，晚期病例的术前化疗和延期手术等的临床的研究。以探讨肾母细胞瘤的发生、演进、转移等生物学特性和组织病理、临床特征、预后因素对提高生存率和生活质量的影响，以…     

nm23—H1蛋白和c-erbB-2蛋白在人肝细胞癌中的表达

应用免疫组化检测68例肝细胞癌（HCC）及其癌旁肝组织中nm23－H1蛋白和c－erbB－2蛋白的表达。结果显示nm23－H1蛋白在癌旁肝组织中均呈强阳性表达，肝细胞癌组织中38／68（56％）例呈阳性表达。阳性产物主要定位于肿瘤细胞胞浆，nm23－H1蛋白表达与HCC肿瘤体积、组织病理学分型及分级无关，而与肝内或肝外转移呈负相关。结果表明nm23-H1在抑制HCC肝内或肝外转移中起着重要作用。有可能成为评价HCC病人预后的一项指标。     

nm23—H1和nm23—H2在人乳腺癌中的表达及其临床意义

目的：研究nm23基因两个亚型表达与乳腺癌发生转移因素之间的关系。方法：用半定量RT-PCR方法，检测30例乳腺癌组织nm23-H1和nm23-H2mRNA的表达，分析其与乳腺癌转移的关系。结果：淋巴结阳性的原发灶组织nm23-1mRNA表达明显低于淋巴结阴性的原发灶组织，Ⅲ期乳腺癌组织nm23-H1mRNA水平较Ⅰ、Ⅱ期的明显低，多因素分析发现淋巴结转移与nm23-H1mRNA的表达有显著性相关。nm23-H2mRNA表达与乳腺癌患者肿瘤大小、淋巴结状况、绝经状况、激素受体状况、TNM分期之间无显著性相关。结论：nm23-H1mRNA的表达强度与乳腺癌淋巴结转移呈负相关，nm23-H1mRNA较nm23-H2mRNA在乳腺癌转移过程中起重要的作用。nm23-H1mRNA表达可能是淋巴结转移的一个重要预测因子。     

nm23—H1基因与乳腺癌转移和预后的关系及其突变的研究

采用免疫组化染色分析100例乳腺癌组织的nm23－H1基因表达与腋窝淋巴结转移和预后的关系，发现阳性表达者的5年无瘤生存率为84．8％（39／46），明显高于阴性表达者的52．9％（18／34），P＜0．01。进一步对20例采用RNA提取、PT－PCR、PCR－SSCP等方法检测乳腺癌组织中nm23－H1基因mRNA表达和突变情况，发现有突变的乳腺癌其基因表达均为阴性，胶窝淋巴结转移均为阳性（P＝0．036）。研究结果提示：nm23－H1基因突变可能易发生于晚期乳腺癌，同时检测nm23－H1基因mRNA表达水平和突变情况可作为判断乳腺癌（尤其是无淋巴结转移乳腺癌）的一项指标。     

鼻咽癌中CD44v6和nm23H1表达的原位杂交研究

目的　探讨CD44v6mRNA和nm2 3H1mRNA表达与鼻咽癌 (NPC)临床意义及其相关性。方法　应用催化信号放大原位杂交方法 ,检测 65例NPC中CD44v6mRNA和nm2 3H1RNA表达 ,结合临床病理指标及随访病例进行研究分析。结果　在NPC中CD44v6mRNA和nm2 3H1mRNA表达阳性率分别为 47 7%和 5 2 3 %。CD44v6mRNA阳性表达和nm2 3H1mRNA阴性表达与NPC原发病灶分期和淋巴结转移均呈正相关 ,患者 5年内复发转移率高 (P <0 0 1) ,5年存活率低 (P <0 0 5 )。CD44v6mRNA表达与nm2 3H1mRNA表达呈负相关。结论　NPC中CD44v6mRNA表达与nm2 3H1mRNA表达具有负调节的协同作用 ,均可作为预测NPC转移、复发和评估预后的重要生物学指标     

MTA1、nm23H1 mRNA表达及突变与卵巢癌淋巴结转移的关系

目的 研究MAT1、nm23H1 mRNA表达及突变与卵巢癌淋巴结转移的关系。方法 应用逆转录－PCR（RT－PCR）和逆转录－PCR－单链构像多态性分析（RT－PCR－SSCP）技术,对8例正常卵巢、20例卵巢癌及其相应的20例淋巴结组织,进行MTA1和nm23H1 mRNA表达及突变的检测。结果 转移卵巢癌原发灶MTA1 mRNA高表达率为100％(7/7),无转移为38．5％（5／13）,P＝0．0103;有癌转移淋巴结高表达率为87．5％（6／7）,无癌转移为23％（3／13）,P＝0．0043;有癌转移淋巴结低表达率为100％（7／7）,无癌转移为38．5％（5／13）,P＝0．0102。MTA1／nm23H1 mRNA表达的相对吸光度值（A值,曾称光密度OD值）的比值随转移而增加。单链构像多态性分析（SSCP）未发现突变。结论 MTA1、nm23H1基因的转录表达与卵巢癌淋巴结转移呈正负相关关系,起着下负调控的重要作用。这两个基因的异常表达是卵巢癌转移中的频发事件而与基因突变无关。     

CD15、CD44v6和nm23H1的mRNA在鼻咽癌中表达的临床意义及相关性

目的　探讨CD15mRNA及其蛋白、CD44v6和nm2 3H1的mRNA表达与鼻咽癌 (NPC)临床意义及其相关性。方法　应用免疫组化和原位杂交CSA方法 ,检测 6 5例NPC中CD15mRNA及其蛋白、CD44v6和nm2 3H 1的mRNA表达 ,结合临床病理指标及随访病例进行研究分析。结果　在NPC中CD15mRNA及其蛋白、CD44v6和nm 2 3H1的mR NA表达阳性率分别为 44.6 %、40 %、47.7%和 5 2 .3 %。CD15mRNA及其蛋白、CD44v6mRNA阳性表达和nm2 3H1mR NA阴性表达与NPC原发病灶分期和淋巴结转移均呈正相关 ,患者 5年内复发转移率高 (P <0 .0 1) ,5年存活率低 (P <0 .0 5 )。CD15mRNA与其蛋白表达和CD44v6mRNA表达呈正相关 ,与 2 3nmH1mRNA表达呈负相关。结论　 (1)NPC中CD15mRNA表达与CD44v6和nm2 3H1的mRNA表达具有调节和负调节的协同作用。 (2 )CD15、CD44v6和nm 2 3H1的mRNA均可作为预测NPC转移、复发和评估预后的重要生物学指标。     

The role of nm23-H1 in the progression of transitional cell bladder cancer.

The nm23 gene was initially cloned as a metastasis suppressor gene, but the clinical relevance of nm23-H1 as a metastasis suppressor or prognostic indicator for human cancers remains enigmatic. Given that gene expression is regulated at the tissue-specific level, we studied the molecular mechanisms of nm23-H1 expression in human bladder cancer cell lines and the clinical importance of protein product (NM23-H1) in association with patient outcome (n = 257) by immunohistochemistry. We demonstrated that nm23-H1 is expressed in bladder cancer cells without genomic alterations. High NM23-H1 expression was found in 39 cases (15.2%), intermediate expression in 119 cases (46.3%), and low NM23-H1 in 99 cases (38.5%). NM23-H1 was inversely related to staging classification or tumor size (P < 0.05), with the most significant difference being observed between pTa tumors and those of pT1-pT3 bladder cancer (P = 0.01). Reduced NM23-H1, defined as intermediate and low levels of expression, tended to have a higher risk of tumor metastasis (P = 0.06) or poor longtime survival (P = 0.07). In the subset of grade 2 bladder tumors, reduced NM23-H1 significantly correlated with the occurrence of tumor metastasis or poor patient survival (P < 0.05). These findings overall suggest that nm23-H1 may play an important role in suppressing the early step of carcinogenesis and thus act as an invasion suppressor for human bladder cancer. A prospective study is required to clarify the potential of the molecular marker in prediction of disease progression.     

Nm23 expression in human gastric cancers - possible correlation of nm23 with lymph-node metastasis

In order to elucidate the relationship between nm23 and metastasis in human gastric cancers, we analyzed gene and protein expression of nm23-H1 using Northern blot and immunohistochemical techniques. nm23-H1 gene expression was identified in 17 out of 19 gastric cancer tissues. The signals in the tumor tissues presenting regional lymph node metastasis seem to be lower than those in the tumor tissues without regional lymph node metastasis, suggesting a role of nm23-H1 in the regional lymph node metastasis in the gastric cancers. However, the protein expression detected immunohistochemically was not correlated to the gene expression, partly because of difficulty in quantifying the amount of protein. Expression of the nm23-H1 gene as well as the nm23-H1 protein in the tumor tissues was higher than those in the corresponding normal mucosae. This suggests a linkage of nm23-H1 in the process of the gastric cancer progression. We also analyzed the sequence abnormalities of the nm23-H1 gene in the gastric cancer tissues using a direct sequencing technique, no mutations were observed.     

Reappraisal of the role of NM23-H1 in colorectal cancers

BACKGROUND AND OBJECTIVES: A number of evidence indicate that downregulation of the nm23-H1 gene may be relevant to metastatic progression of many kinds of human cancer. However, its role in colorectal cancers remains controversial. To address the issue, this study was performed to investigate the clinical relevance of nm23-H1 in patients with colorectal cancers. METHODS: Immunohistochemical expression of nm23-H1 protein product (NM23-H1) was studied in a total of 146 colorectal cancer patients and compared for its prognostic value at a mean follow-up of 54 months. RESULTS: There was no apparent correlation between NM23-H1 expression and clinicopathological indicators, including Dukes category, lymphatic metastasis, distant metastasis, histological grading, and tumor location (P < 0.1, respectively). In addition, determination of NM23-H1 expression status did not provide independent prognostic information compared with conventional pathological staging. CONCLUSIONS: The results indicate that nm23-H1 gene does not play an important part in the progression of colorectal carcinogenesis.     

Somatic allelic deletion of nm23 in human cancer

Tumor progression to the metastatic phenotype is accompanied in certain cell types by reduced expression of the nm23 gene. We have localized human nm23-H1 to chromosome 17 by somatic cell hybrid analysis. Regional localization in the CEPH database and in situ hybridization is reported. Somatic allelic deletion of nm23-H1 was observed in human breast, renal, colorectal, and lung carcinoma DNA samples, as compared to DNA from matched normal tissues. A homozygous deletion of nm23-H1 was observed in a lymph node metastasis of a colorectal carcinoma, indicating that nm23-H1 can be recessively inactivated. The data identify nm23-H1 as a novel, independent locus for allelic deletion in human cancer, a characteristic shared with previously described suppressor genes.     

The association between nm23-H1 expression and survival in patients with esophageal squamous cell carcinoma.

The nm23 gene is a potential metastasis suppressor gene originally identified using a murine melanoma cell line. The expression of nm23-H1 protein was examined immunohistochemically in 50 eligible patients with esophageal squamous cell carcinoma (ESCC). The expression was not correlated with other prognostic factors including lymph node metastases; however, overall survival rates of nm23-H1-negative patients were significantly shorter than those of nm23-H1-positive patients (P < 0.05). Furthermore, reduced expression of nm23-H1 was associated with shorter overall survival in patients with involved lymph nodes (P < 0.01), but not in patients without involved lymph nodes. These data support the conclusion that reduced expression of nm23-H1 may be associated with poor prognosis of ESCC patients, suggesting the value of nm23-H1 expression as a prognostic marker for ESCC patients, especially ESCC patients with involved lymph nodes.     

Expression and mutational analysis of Nm23-H1 in liver metastases of colorectal cancer.

It has been proposed that nm23-H1, a candidate suppressor gene for metastasis, plays an important role in metastasis formation of human tumours. In order to investigate its role in the progression of colorectal cancer, we analysed 22 liver metastases of this malignancy with respect to mutational changes, loss of heterozygosity and expression levels of nm23-H1. Although genetic alterations in nm23-H1 have recently been described in those colorectal adenocarcinomas which give rise to distant metastases, we were unable to detect any mutation in the coding sequence of nm23-H1 in the metastatic tissue itself. We further analysed the metastases with respect to allelic deletions at the chromosomal locus of nm23. However, no loss of heterozygosity could be detected in ten informative cases. Moreover, the mRNA expression levels of nm23-H1 in the metastatic tissues were not significantly different from those in normal colon mucosa. Thus, although nm23-H1 might be involved in metastasis suppression of certain tumour types, in colorectal tumour progression its role remains to be determined.     

Clinical significance of nm23-H1 proteins expressed on cell surface in non-Hodgkin's lymphoma.

The nm23 gene was isolated as a metastasis suppressor gene that exhibits low expression in high-level metastatic cancer cells. Its gene is related to the prognosis of acute myelogenous leukemia (AML) and non-Hodgkin's lymphoma (NHL). In this study, we examined the expression of nm23-H1 protein on the lymphoma cell surface of NHL. In 28 of 108 cases (25.9%), we observed > or = 20% of cell surface nm23-H1 protein expression and expression was especially high in peripheral T cell lymphomas and extranodal NK/T cell lymphomas. We also observed a significant correlation between serum nm23-H1 level and cell surface nm23-H1 expression levels. In patients with high levels of cell surface nm23-H1 expression, overall and progression-free survival rates were significantly lower than those in patients with low surface nm23-H1 expression levels. When surface nm23-H1 and serum nm23-H1 were combined, patients with high levels of both exhibited a poorer prognosis than patients with a high level of one or the other. These results indicate that in addition to serum nm23-H1, cell surface nm23-H1 may be used as a prognostic factor in planning a treatment strategy. The nm23-H1 protein appears to be intimately related to biological aggressiveness of lymphoma and, therefore, might be a molecular target of NHL treatment.     

The NM23 gene and its expression in oral squamous cell carcinoma.

The murine nm23, a putative metastasis suppressor, has three human homologues, NM23-H1, -H2, and -H3b. Several reports have suggested a low metastatic potential for neoplasms with a high expression of NM23-H1 gene, while other studies have not shown this relationship. These apparent differences in the role of NM23 in metastasis suppression might be explained by unability to discriminate between the expression of the two genes NM23-H1 and NM23-H2. The NM23-H2 product is not related to tumor progression and metastasis suppression. Two studies on human oral squamous cell carcinoma (OSCC) have been reported, both showing the NM23 product to be a metastasis suppressor factor. However, none of these two studies distinguished NM23-H1 from NM23-H2. The aim of this study was to detect the protein expression pattern of NM23-H1 product in 24 OSCCs by immunohistochemistry in paraffin-embedded tissues using a monoclonal antibody non-cross-reactive with NM23-H2. The NM23-H1 positive group showed lower frequency of lymph node metastasis, and a better grading than the NM23-H1 negative group supporting the role of NM23-H1 as metastasis suppressor factor which may be useful for predicting tumor metastasis in OSCC.     

膀胱癌中nm23-H1基因突变及表达的意义

目的：探讨ｎｍ２３－Ｈ１基因在膀胱癌中突变及表达的意义。方法：应用半定量逆转录聚合酶链反应（ＲＴ－ＰＣＲ）和银染单链构象多态性（ＳＳＣＰ）方法检测ｎｍ２３－Ｈ１基因在２５例膀胱癌组织及１５例对照组织中突变和表达情况。结果：对照粘膜中未检测出ｎｍ２３－Ｈ１基因突变,而在２５例膀胱癌组织中发现６例出现ＰＣＲ产物单链泳动状态异常,异常率为２４％。癌组织和对照组织均有ｎｍ２３－Ｈ１基因ｍＲＮＡ的表达,８８     

食管鳞状细胞癌中nm23-H1和p53蛋白表达及其相互关系

目的:探讨食管鳞癌组织中p53和nm23-H1蛋白的表达与癌组织分化浸润转移的关系,以及探讨两者之间的相关性,并进一步分析癌组织中p53和nm23-H1蛋白表达对食管癌患者的预后意义。方法:采用免疫组织化学(S-P法)方法对100例人食管鳞癌组织中的p53和nm23-H1蛋白的表达情况进行检测。结果:100例食管鳞癌组织中,nm23-H1阳性表达者70例(阳性率为70%),p53阳性表达者64例(阳性率为64%)。nm23-H1蛋白表达与食管癌淋巴结转移有关(P<0.025),与食管鳞状细胞癌的分化程度、肿瘤部位、浸润深度、病变长度以及患者性别、年龄无关(P>0.05)。p53蛋白表达与食管鳞状细胞癌的分化程度、浸润深度有关(P<0.05),与食管癌淋巴结转移、肿瘤部位、病变长度、患者性别、年龄无关(P>0.05)。高分化鳞癌组织中p53明显低表达(29.2%);低分化鳞状细胞癌组织中p53表达明显增高(71.4%)。食管外膜受累者p53表达较高(56%);仅发生食管粘膜和(或)粘膜下浸润组的癌组织中未发现有p53蛋白的表达。食管癌组织中nm23-H1蛋白低(高)表达与p53高(低)表达之间有明显相关性(P<0.01)。nm23-H1和p53蛋白表达亦与食管癌的TNM分期密切相关(P<0.05)。食管癌TNM分期越晚,其癌组织中nm23-H1蛋白表达越低,p53蛋白表达越高。结论:nm23-H1基因低表达与p53基因高表达可能在食管鳞状细胞癌浸润转移过程中发挥重要作用。nm23-H1可以作为食管鳞状细胞癌患者预后的基因标记,其蛋白表达产物的检测可以用于患者预后的判断,并为患者治疗方案的制定提供参考。