全反式维甲酸诱导肝癌细胞SNU-398表达nm23-H1

目的 研究全反式维甲酸(all Hans retinoic acid,ATRA)诱导肝癌细胞SNU-398表达nm23H1及其可能的分子机制.方法 ATRA处理肝癌细胞株SNU-398后不同时间采用定量RT-PCR检测nm23-H1的表达水平.用ATRA受体(retinoic acid receptor,RAR)的选择性激动剂与阻滞剂处理SNU-398细胞,观察nm23-H1表达与细胞侵袭力的变化.克隆nm23-H1启动子系列缺失突变片断,Luciferase报告基因检测ATRA对启动子活性的影响.结果 ATRA能够明显上调nm23-H1的转录水平,并具有时间依赖关系.RARγ激动剂能够明显促进nm23-H1转录水平的上调,并抑制SNU-398的体外侵袭力.启动子片断-1 260 bp的活性在ATRA的诱导下较对照上调3.5倍左右.结论 ATRA能够通过RARγ上调nm23-H1的转录以及体外抑制肝癌细胞株SNU-398的侵袭力.nm23-H1启动子潜在的ATRA调控位点位于-478至-1 260bp之间.     

老年结肠癌病人外周血CK-20 mRNA表达与癌组织中nm23-H1表达的关系

目的探讨老年结肠癌病人手术前后外周血CK-20 mRNA表达情况,以及与nm23-H1表达之间的关系。方法采用逆转录多聚酶链式反应方法（RT-PCR）,以CK-20 mRNA为靶基因,检测了结肠癌病人48例,结肠良性疾病组病人20例;同时采用免疫组化法检测48例结肠癌病人术后肿瘤标本中nm23-H1的表达情况。结果结肠良性疾病组（20例）,术前术后CK-20 mRNA表达均为阴性。结肠癌组（48例）术前CK-20 mR-NA阳性率25%（12/48）,术后阳性率41%（20/48）,术后明显高于术前（P〈0.05）。nm23-H1在CK-20 mRNA表达阳性病例中表达率为15%（3/20）,在CK-20 mmRNA表达阴性病例中,阳性率为64%（18/25）,二者差异非常显著（P〈0.01）。结论结肠癌病人（B期、C期）术前有部分病人血中CK-20 mRNA表达阳性,说明血中有游离癌细胞。术后阳性率明显升高,说明术中牵拉、刺激、挤压,可能增加癌细胞扩散的可能性。nm23-H1的表达与血中CK-20 mRNA的表达呈负相关。     

Loss of heterozygosity of thenm23-H1 gene in human renal cell carcinomas

This study evaluates the potential contribution of thenm23-H1 gene to malignant transformation in patients with renal cell carcinoma. Using specific oligonucleotide primers for thenm23-H1 microsatellite repetitive sequence, gene instability was followed by polymerase chain reaction/loss of heterozygosity assay on 54 tumor specimens and the corresponding normal tissue samples. We also determined, immunohistochemically, the relative concentration and localization of thenm23-H1 protein product. From 77.7% informative cases, DNA from 6 tumors exhibited loss of heterozygosity, regardless of the tumor stage (TNM). Out of 39 samples analyzed, 30 were negative for Nm23-H1 protein, while the others were only slightly positive. No correlation with tumor stage was found. Normal renal tissue was also negative for this protein. Our results provide the evidence for loss of heterozygosity, followed by means of microsatellite tandem-repeat polymorphism, at thenm23-H1 locus in renal cell carcinoma. However, since no correlation was found between the tumor stage or metastatic potential on the one hand, and allelic loss and specific protein expression on the other, it seems thatnm23-H1 does not play a key role in the invasiveness of this tumor type.Abbreviations PCR polymerase chain reaction - LOH loss of heterozygosity     

nm23—H1的表达与大肠癌淋巴结转移的关系

应用S-P免疫组织化学染色观察nm(23)基因亚型nm(23)-H1在大肠癌中的表达,结果大肠癌中nm(23)-H1表达的阳性率为72.2%(39/54),相应的癌旁正常组织为阴性。在与临床病理指标相关性分析中发现无淋巴结转移者nm(23)-H1表达阳性率高于有淋巴结转移者,差别有显著意义(P<0.025)。结果表明nm(23)-H1基因低表达与肿瘤进展与预后不良有关。     

胃癌组织KAI 1和nm23-H1蛋白的表达意义

目的:观察胃癌组织中KAI 1和nm23-H1蛋白的表达与临床病理生物学的关系,探讨KAI 1蛋白在胃癌发生、发展中的作用．方法:应用兔抗人KAI 1多克隆抗体和鼠抗人nm23-H1 单克隆抗体对87例手术切除胃癌标本以PV-9000免疫组化二步法进行染色,用x2检验进行统计学分析．结果:伴有淋巴结转移的胃癌组织中KAI 1蛋白表达阳性率(60％,39／65)明显低于无淋巴结转移的胃癌组织(95％,21／22,P<0．05),早中期胃癌组织中KAI 1蛋白表达阳性率(94％,16／17)显著高于晚期胃癌组织(63％, 44／70,P<0．05),KAI 1蛋白高表达者其生存期亦较长 (P<0．05);伴有淋巴结转移的胃癌组织中nm23-H1蛋白表达阳性率明显低于无淋巴结转移的胃癌组织(18％ vs 77％,P<0．05),早中期胃癌组织nm23-H1蛋白表达阳性率明显高于晚期胃癌组织(65％vs26％,P<0．05)．结论:KAI 1和nm23-H1蛋白均与胃癌侵袭转移有关, 且KAI 1表达与胃癌患者预后密切相关,将两种指标联合检测,可作为正确判断胃癌患者预后,指导临床治疗的分子生物学指标．     

p16和nm23-H1在胃癌中的表达及其临床应用

目的 探讨p16和nm23-H1在胃癌中的表达规律及其临床意义。方法 应用免疫组织化学LSAB方法,对65例胃癌中p16和nm23-H1蛋白的表达进行了观察。结果 p16的表达与胃癌的分化程度和预后呈正相关,与浸润、淋巴结转移呈负相关。生物学行为有关,可能成为胃癌诊断和判断预后的重要的分析生物学检测指标。     

大肠癌中nm23-H1的表达及其与临床病理特征的关系

目的:观察nm23-H1的表达与临床病理特征的关系,探讨nm23-H1的表达与大肠癌发生、发展、转移的作用.方法:选取行结、直肠癌根治术的患者63例,并取腺瘤组织16例做对照.应用免疫组化S-P法检测大肠癌患者癌组织、同源癌旁组织及正常黏膜组织和大肠腺瘤组织nm23-H1的表达.结果:nm23-H1在癌组织中表达(58.7%)显著低于癌旁组织(90.5%)、正常黏膜组织(96.0%)及腺瘤组织(93.8%)(P＜0.05).在大肠癌组织中,无淋巴结转移者nm23-H1表达(73.3%)显著高于有淋巴结转移者(45.5%)(P＜0.05).大肠癌中nm23-H1表达与肿瘤分化程度呈正相关(r=0.192,P＜0.05),与肿瘤浸润深度呈负相关(r=-0.263,P＜0.05).nm23-H1表达程度与患者年龄、性别、肿瘤大体分型、组织学类型、同期肿瘤大小均无关.结论:nm23-H1表达下调是大肠癌发生、发展中的重要分子生物学事件,可作为提示肿瘤分化、侵袭和淋巴结转移的一项指标.     

Relationship between expression of CD44v6 and nm23-H1 and tumor invasion and metastasis in hepatocellular carcinoma

ＩＮＴＲＯＤＵＣＴＩＯＮＣＤ４４ｉｓａｃｅｌｓｕｒｆａｃｅｔｒａｎｓｍｅｍｂｒａｎｅｇｌｙｃｏｐｒｏｔｅｉｎ．Ａｓａｋｉｎｄｏｆａｄｈｅｓｉｖｅｍｏｌｅｃｕｌｅ,ｉｔｐａｒｔｉｃｉｐａｔｅｓｉｎｃｅｌｃｅｌａｎｄｃｅｌｍａｔｒｉｘａｄｈｅｓｉｏｎ...     

胃癌细胞周期和nm23-H1基因表达与淋巴结转移的关系

目的:探讨胃癌组织nm23- H1 基因表达与细胞周期及其淋巴转移的关系。方法:收集手术切除正常胃黏膜及胃癌组织标本各28 例,采用流式细胞技术进行细胞周期分析及nm23 -H1蛋白半定量检测。结果:细胞周期分析显示正常胃黏膜组织均为二倍体;28例胃癌组织中有18 例为异倍体,14/18例(77.78%)异倍体瘤中有发生淋巴结转移,10 例非异倍体瘤中仅有3 例出现淋巴结转移(30%),两者比较有显著性差异(P<0.05)。正常胃粘膜组织增殖指数(PI)为2.04%,胃癌组织PI为12.69%±6.78%。其中淋巴结转移阳性组胃癌组织PI为14.86%±8.41%,显著高于淋巴结转移阴性组胃癌组织(PI为10.51%±4.89%)(P<0.05)。正常胃粘膜组织nm23 基因表达为阴性,胃癌组织nm23 基因表达(FI)为0.73±0.36,其中淋巴结转移阳性组FI 为0.42±0.24,淋巴结转移阴性FI 为1.04±0.17,两者比较有显著性差异(P< 0.05)。非异倍体组胃癌nm23基因表达(FI)为1.01±0.21,显著高于异倍体组胃癌(FI为0.45±0.29)(P<0.05)。结论:胃癌淋巴转移与胃癌组织的异倍性、高增殖活性及nm23 H1基因表达缺失有关。     

nm23-H_1、CerbB-2的表达与食管癌预后的关系

用免疫组化的方法分析 91例食管癌 (鳞癌 84例 ,腺癌 3例 ,未分化癌 4例 )转移抑制基因 ( nm2 3)和癌基因 Cerb B- 2蛋白表达与肿瘤临床、病理各指标间的关系 ,探讨其在食管癌发生中的相互关系和影响。结果显示 :转移抑制基因 nm2 3- H1 和原癌基因 Cerb B- 2染色均定位于细胞浆 ,两者均与淋巴结转移、预后有显著相关性 ,两者表达无相关关系。在无淋巴结转移组 ,Cerb B- 2蛋白表达亦和预后有显著负相关。认为 nm2 3- H1 高表达或 Cerb B- 2低表达者 ,淋巴结转移率低 ,术后生存率高 ,预后较好 ;Cerb B- 2可作为一个独立的预后指标 ,无论有无淋巴结转移 ,Cerb B- 2蛋白高表达预后均差     

Role of intrahepatic tumor control in the prognosis of patients with hepatocellular carcinoma and extrahepatic metastases

Background and Aim: There has been little information about the long‐term outcome and prognostic factors in patients with hepatocellular carcinoma (HCC) and extrahepatic metastases. The purpose of this study was to investigate the clinical factors affecting survival after extrahepatic metastasis and to determine the survival benefit of controlling intrahepatic HCC. Methods: Between 2004 and 2009, a total of 240 consecutive patients with HCC and extrahepatic metastasis were recruited. Based on tumor extent, performance, and hepatic function, the patients underwent locoregional and/or systemic treatments. The treatment response of the intrahepatic tumor after extrahepatic metastasis and other prognostic parameters were analyzed retrospectively. Results: During the mean follow up of 276 days, 222 patients died; the median survival time was 146 days. Multivariate analysis revealed that Child–Pugh class A, smaller hepatic tumor size, absence of portal venous invasion, single metastatic organ involvement, and objective treatment response of the intrahepatic tumor were the favorable prognostic factors for survival. Of the 183 evaluable patients, 24 achieved complete or partial response for intrahepatic tumors after treatment. The overall survival for the 24 responders was significantly improved, with a median of 521 days, as compared to 170 days for the remaining 159 patients without objective tumor response. The leading cause of death was progressive intrahepatic tumor. Conclusions: Intrahepatic tumor status and hepatic reserve are among the significant predictors of survival in patients with HCC and extrahepatic metastases. This study indicates that even in patients with metastases from advanced HCC, therapeutic approaches to control intrahepatic tumors are important in improving patient survival.     

Clinical features of hepatocellular carcinoma with extrahepatic metastases

BACKGROUND: There are few detailed clinical reports about extrahepatic metastases of hepatocellular carcinoma (HCC). The purpose of the present study was to elucidate the clinical features of extrahepatic metastases of HCC. METHODS: The clinical records of 482 patients who had been diagnosed as having HCC during the period from January 1995 to March 2001 were retrospectively reviewed. Extrahepatic metastases had been detected in 65 patients. Clinical features of those 65 patients were analyzed. RESULTS: Patients with extrahepatic metastases had more advanced intrahepatic tumors at the first diagnosis of HCC: 73.8% of the patients with extrahepatic metastases had tumors of intrahepatic tumor stage T3 or T4 according to the TNM classification, while only 28.5% of the patients without extrahepatic metastases had tumors of T3 or T4 (P < 0.001). Vessel invasion was also detected at the first diagnosis of HCC more frequently in the patients with extrahepatic metastasis (P < 0.001). The frequent metastatic sites were lung (53.8%), bone (38.5%), and lymph node (33.8%). Other metastatic sites were the adrenal gland, peritoneum, skin, brain and muscle. The median survival time and 1-year survival rate were 7 months (range: 1-59 months) and 24.9%, respectively. Patients with Child-Pugh grade B and C (P = 0.0018) and patients with positive serum alpha-fetoprotein (P = 0.011) had significantly poor prognosis. CONCLUSIONS: Extrahepatic metastases of HCC are not rare. The possibility of extrahepatic metastases and the clinical features of extrahepatic metastases should be considered when examining patients with HCC, particularly those with advanced intrahepatic tumors, to enable precise evaluation of the spread of HCC and determination of the appropriate treatment method.     

肝细胞癌p53及nm23-H1 mRNA表达的意义

目的探讨ｐ５３,ｎｍ２３Ｈ１与原发性肝细胞癌（ＨＣＣ）发生发展的关系．方法运用原位分子杂交技术对４９例ＨＣＣ中ｐ５３和ｎｍ２３Ｈ１基因ｍＲＮＡ进行检测,并结合临床病理特征进行分析．结果ｐ５３ｍＲＮＡ杂交阳性２３例,占４６９％;ｐ５３ｍＲＮＡ过表达与肿瘤的肝内转移．包膜侵犯及Ｅｄｍｏｎｄｓｏｎ分级相关（Ｐ＜００５）;ｎｍ２３Ｈ１ｍＲＮＡ阳性表达２７例,占５５１％;ｎｍ２３Ｈ１ｍＲＮＡ表达与肿瘤肝内转移及ＴＮＭ分期呈负相关（Ｐ＜００５）;同时发现ｐ５３ｍＲＮＡ过表达和ｎｍ２３Ｈ１ｍＲＮＡ低表达在ＨＣＣ肝内转移中具有协同作用．结论ｐ５３和ｎｍ２３Ｈ１参与ＨＣＣ的发生发展,ｐ５３过表达及ｎｍ２３Ｈ１低表达提示ＨＣＣ肝内转移．     

原发性肝细胞癌中CD44v6和nm23H1基因的转录表达及临床意义

研究CD44v6 mRNA和nm23H1 mRNA表达与肝细胞癌（HCC）侵袭转移和预后的关系。应用原位杂交方法，检测分析HCC组织中CD44v6 mRNA和nm23H mRNA表达。99例HCC中，CD44v6 mRNA和nm23H1 mRNA表达阳性率分别为41．4％和76．8％。CD44v6mRNA表达与nm23H1mRNA表达呈负相关。CD44v6和nm23HmRNA表达均与HCC侵袭转移倾向和预后相关。检测CD44v6和nm23H1表达有可能成为HCC 侵袭转移和预后判断的病理生物学指标。     

Prognostic significance of co‐expression of nm23 and p57 protein in hepatocellular carcinoma

Aim: To investigate the unbalance of proliferation and apoptosis and the functions of cell‐cycle proteins and apoptotic factor in metastasis of hepatocellular carcinoma (HCC) and their effect in prognosis. Methods: Proliferation index and apoptosis index, as well as seven relatively molecular markers, namely p15, p34, p53, p57, p73, survivin and nm23, were evaluated by immunohistochemistry and TUNEL in HCC tissues and compared to adjacent non‐cancerous tissues and normal liver tissues. Furthermore, the prognostic significance by follow‐up and mutual relationships for each clinicopathologic factor and molecular marker were analysed. Results: The dysregulation between proliferation and apoptosis and the abnormal expression of seven molecular markers were observed in HCC tissues. The unbalance of proliferation and apoptosis and abnormal expressions of p15, p34, p57 and nm23 were correlated with TNM stage and extrahepatic metastasis. In particular, the abnormal co‐expression of nm23/p57 correlated with advanced TNM stage and bigger tumor size and was an independent prognostic factor of HCC. Conclusion: The unbalance of proliferation and apoptosis and abnormal expression of cell‐cycle proteins promote metastasis of HCC. Moreover, the abnormal co‐expression of nm23/p57 may be a useful molecular marker for metastasis and unfavourable prognosis for HCC.     

大肠癌组织nm23-HI p53 PCNA的表达

目的研究大肠癌组织ｎｍ２３ＨＩ，ｐ５３，ＰＣＮＡ的表达意义及其与肿瘤浸润转移的关系．方法１９９１年３月～１９９６年５月采用免疫组织化学方法检测７４例（男３９例，女３５例，平均年龄５３２岁，术前未做化疗及放疗）大肠癌组织（石蜡切片，厚４μｍ）中ｎｍ２３Ｈ１，ｐ５３，ＰＣＮＡ以及Ⅳ型胶原的表达情况．结果大肠癌ｎｍ２３Ｈ１，ｐ５３，ＰＣＮＡ的阳性率分别为７１６％、５２７％和８１１％．ｎｍ２３Ｈ１低表达与淋巴结转移有关（Ｐ＜００５），在Ⅳ型胶原表达不同的肠癌中ｎｍ２３－Ｈ１的表达无明显差异；ｐ５３和ＰＣＮＡ过表达与浸润程度和淋巴结转移有关（Ｐ＜００５）．结论ｎｍ２３ＨＩ低表达可作为预测大肠癌转移的较好指标．ｐ５３过表达在浸润转移过程及细胞增殖中均起重要作用．     

Expression of nm23 gene in hepatocellular carcinoma tissue and its relation with metastasis

Ｅｘｐｒｅｓｓｉｏｎｏｆｎｍ２３ｇｅｎｅｉｎｈｅｐａｔｏｃｅｌｕｌａｒｃａｒｃｉｎｏｍａｔｉｓｓｕｅａｎｄｉｔｓｒｅｌａｔｉｏｎｗｉｔｈｍｅｔａｓｔａｓｉｓＨＵＡＮＧＢｅｉ,ＷＵＺｈｏｎｇＢｉａｎｄＲＵＡＮＹｏｕＢｉｎｇＳｕｂｊｅｃｔｈｅａｄｉ...