组织因子 mRNA在肝癌患者组织中表达升高的意义

目的 检测组织因子(TF)在肝癌组织中的表达并探讨其临床意义.方法 采用RT-PCR方法检测肝癌、癌旁及对照组肝组织(各27例)中TF mRNA的表达,并结合临床病理资料进行分析.结果 TF在肝癌组织中的表达阳性率及相对表达强度分别为62.96%(17/27)和0.567±0.268,均较癌旁组织的33.33%(9/27)和0.469±0.184及对照组肝组织的29.63%(8/27)和0.353±0.121高(P＜0.05),其相对表达强度与肿瘤大小、肝内和肝外转移及门静脉癌栓有关(P＜0.05),而与患者性别、AFP、HBsAg、是否合并肝硬变、肿瘤分化程度、癌灶数目、包膜浸润及淋巴转移均无关(P＞0.05).结论 TF在肝癌组织中的表达升高与部分侵袭转移指标有关,提示其可能参与了肝细胞癌的发生及侵袭、转移.     

Expression of Hepatocyte Growth Factor Activator Inhibitor Type 1 in Human Hepatocellular Carcinoma and Postoperative Outcomes

Background  

Hepatocyte growth factor activator inhibitor type 1 (HAI-1), one of the Kunitz-type serine protease inhibitors, has an important role in cancer progression through regulation of the activity of hepatocyte growth factor. HAI-1 is expressed in hepatocellular carcinoma (HCC) to various degrees. Investigation of the relationship between HAI-1 expression and clinicopathological features of HCC may contribute to improved treatment outcomes for HCC through understanding the mechanism of tumor progression or improvement in the prediction of tumor malignancy.     

COX-2与HIF-1α在肝癌中的表达与相关性

目的研究肝癌中环氧合酶-2(COX-2)和缺氧诱导因子-1α(HIF-1α)表达的相关性,探讨选择性COX-2抑制剂抑癌作用的可能机理。方法通过免疫组化染色检测53例肝癌标本中COX-2和HIF-1α的表达;利用不同浓度的选择性COX-2抑制剂美洛昔康对在正常和氯化钴模拟缺氧条件下培养的肝癌SMMC-7721细胞进行处理,Western blot法分别检测各组HIF-1α的表达情况。结果53例标本中COX-2表达强阳性率为41.5%(22/53),表达弱阳性率为20.8%(11/53),表达阴性率为37.7%(20/53);HIF-1α表达强阳性率为34.0%(18/53),表达弱阳性率为34.0%(18/53),表达阴性率为32.1%(17/53)。COX-2和HIF-1α的表达呈正相关(r=0.44,P<0.01)。常氧条件下HIF-1α表达相对值为0.185±0.057,经美洛昔康处理后HIF-1α不表达。缺氧刺激下HIF-1α表达相对值升高至1.011±0.131,而加入美洛昔康后明显降低(P<0.05),且随着美洛昔康浓度的增加,降低越明显(P<0.05)。结论美洛昔康不仅能够抑制常氧条件下HIF-1α的表达,而且呈浓度依赖性地抑制缺氧条件下HIF-1α表达的上调,选择性COX-2抑制剂的抑癌作用机理可能部分是由HIF-1α介导的。     

Normoxically Overexpressed Hypoxia Inducible Factor 1-Alpha is Involved in Arsenic Trioxide Resistance Acquisition in Hepatocellular Carcinoma

Background

The aim of this study was to examine the underlying signaling mechanisms of arsenic trioxide (ATO)-mediated anticancer effects and the responsible biomarker(s) for the acquired resistance in human heptatocellular carcinoma (HCC).

Materials and Methods

The therapeutic effects of ATO were examined using 2 characteristically distinct HCC cell lines, Hep-J5 (overexpressing HIF-1α/GRP78) and SK-Hep-1 (the matched control). ATO-mediated proliferation inhibition, oxidative stress, and apoptosis were analyzed using flowcytometric analysis and western blotting. The role of HIF-1α and GRP78 in HCC resistance to ATO treatment was determined using RNA silencing and inhibitor approaches.

Results

SK-Hep-1 cells, lacking both HIF-1α and GRP78 expressions were responsive to ATO-induced apoptosis via an oxidative-nitrosative mechanism. Intracellular glutathione depletion and lipid peroxidation have been identified as the early cascade of events preceding apoptosis via cytochrome c release and the severe drop of mitochondrial membrane potential (MMP). Conversely, Hep-J5 cells, with normoxic coexpression of HIF-1α and GRP78, were resistant to ATO-induced apoptosis. GRP78-silenced Hep-J5 cells remained resistant to ATO treatment. In contrast, ATO resistance in Hep-J5 cells was overcome by the addition of YC-1, a HIF-1α inhibitor.

Conclusions

HIF-1α was identified as the major positive modifier for ATO resistance acquisition in HCC, and it represents a prime molecular target for overcoming ATO resistance.     

肾细胞癌中转录因子E2F-1表达的意义

目的探讨转录因子E2F-1在肾癌中的表达及其临床意义。方法应用免疫组化方法检测E2F-1在48例肾癌组织和12例正常肾组织中表达；应用DNA图像定量分析技术进行肾癌中DNA含量检测和细胞周期分析。结果肾癌组织中E2F-1阳性表达率为72．9％，显著高于正常肾组织的41．7％（P〈O．05）；E2F-1表达与肾癌的临床分期、肿瘤大小、淋巴结转移、DNA含量和S期细胞比率均密切相关，但与肾癌病理类型无显著相关性。结论E2F-1异常高表达在肾癌发病机制中起着重要作用，对肾癌生物学行为有-定的预测评估价值。     

血管内皮生长因子和基质金属蛋白酶-9在肝细胞癌中的表达及其意义

目的研究血管内皮生长因子(VEGF)与基质金属蛋白酶-9(MMP-9)在肝细胞癌中的表达,并探讨其与肝细胞癌复发、转移的关系.方法采用免疫组化ABC法对50例肝细胞癌组织和30例正常肝组织中VEGF及MMP-9蛋白的表达进行检测.结果VEGF和MMP-9在肝细胞癌组织中的表达阳性率分别为86.0%(43/50)和68.0%(34/50),明显高于正常肝组织中的表达阳性率53.3%(16/30)和33.3%(10/30).差异有统计学意义(P＜0.05);VEGF的表达与MMP-9的表达呈显著正相关(r＝0.98,P＜0.01),二者的协同表达与肝细胞癌的淋巴结转移及包膜形成有关(P＜0.05).结论VEGF和MMP-9在肝细胞癌的生长、侵袭和转移过程中起着重要作用,对预测肝细胞癌复发、转移有一定意义.     

E2F1蛋白在病理性瘢痕组织中的表达

目的增生性瘢痕和瘢痕疙瘩是临床上常见的病理性瘢痕,是创伤后过度愈合反应的结果,以成纤维细胞的异常增殖及合成分泌大量细胞外基质为特征,其形成机理尚不清楚,研究表明基因失调是其中的关键.E2F基因是细胞周期G1向S期过渡的重要调控因子,在调节细胞周期进程和调节细胞增殖过程中起着关键作用.本实验的目的是检测E2F1基因在病理性瘢痕组织中的表达,以正常皮肤组织做对照,初步探讨E2F1在病理性瘢痕形成中的生物学作用.方法利用免疫组化ABC法检测正常皮肤、成熟瘢痕、增生性瘢痕和瘢痕疙瘩组织中E2F1蛋白的表达,并进行统计学分析.结果增生性瘢痕和瘢痕疙瘩组织中E2F1蛋白表达两组间无明显差异,与正常皮肤、成熟瘢痕对照组比较均有显著性差异(P＜0.01).结论 E2F1蛋白表达在病理性瘢痕组织中增高,促进瘢痕组织中细胞的增生,对病理性瘢痕的形成可能起着重要作用.     

E2F1蛋白在病理性瘢痕组织中的表达

目的　增生性瘢痕和瘢痕疙瘩是临床上常见的病理性瘢痕 ,是创伤后过度愈合反应的结果 ,以成纤维细胞的异常增殖及合成分泌大量细胞外基质为特征 ,其形成机理尚不清楚 ,研究表明基因失调是其中的关键。E2F基因是细胞周期G1向S期过渡的重要调控因子 ,在调节细胞周期进程和调节细胞增殖过程中起着关键作用。本实验的目的是检测E2F1基因在病理性瘢痕组织中的表达 ,以正常皮肤组织做对照 ,初步探讨E2F1在病理性瘢痕形成中的生物学作用。方法　利用免疫组化ABC法检测正常皮肤、成熟瘢痕、增生性瘢痕和瘢痕疙瘩组织中E2F1蛋白的表达 ,并进行统计学分析。结果　增生性瘢痕和瘢痕疙瘩组织中E2F1蛋白表达两组间无明显差异 ,与正常皮肤、成熟瘢痕对照组比较均有显著性差异 (P <0 .0 1)。结论　E2F1蛋白表达在病理性瘢痕组织中增高 ,促进瘢痕组织中细胞的增生 ,对病理性瘢痕的形成可能起着重要作用     

抗血管内皮生长因子抗体对实验性肝癌的生长抑制作用

目的了解抗血管内皮生长因子(VEGF)抗体对人肝癌的生长抑制作用.方法在已建立的人肝癌裸鼠皮下种植瘤的瘤灶旁,注射抗VEGF抗体,观察肿瘤生长情况,用CD31的免疫组化方法检测肿瘤内部的微血管密度(iMVD),用原位末端转移酶标记技术检测凋亡的肿瘤细胞.结果实验结束后1周,实验组和对照组肿瘤大小(长×宽)是(26.46±19.81) mm2和(105.77±17.40) mm2(P<0.001),2周后是(45.20±23.02) mm2和(150.77±77.41) mm2(P<0.05),而此时肿瘤的iMVD是(2 311±120)个/mm2和(3 900±328)个/mm2 (P<0.001); 肿瘤细胞凋亡指数是15.31% 和 6.83%(P<0.005).结论抗VEGF抗体能通过抑制肿瘤微血管的生长,抑制实验性人肝癌的生长,其实质是增加了肿瘤细胞凋亡.     

多药耐药基因mdr1在肝细胞性肝癌中的表达及其意义

目的　探讨肝细胞性肝癌 (HCC)中多药耐药基因mdr1的表达及其与肝癌临床病理特征、肿瘤多药耐药和患者预后的关系。方法　用免疫组化染色方法检测 5 6例HCC细胞中mdr1基因的表达 ,并结合临床病理指标进行统计分析。结果　 5 6例HCC病例中mdr1基因的表达 :癌旁组织中 19例阳性 (3 3 .9% ) ,癌组织中 3 0例阳性 (5 3 .6% ) ,两者比较差异有显著性 (χ2 =4.3 9,P<0 .0 5 )。 48例初治患者中 2 2例阳性 (4 5 .8% ) ,8例复发者均为阳性 (10 0 % )。按肿瘤大小、数目、包膜有无、癌栓有无、分化程度、HBsAg等分组 ,其间mdr1表达差异无统计学意义。mdr1表达阳性组与阴性组 1、2、3年生存率比较 ,其差异无统计学意义。结论　mdr1在HCC中表达阳性率为 5 3 .6% ,其表达与肿瘤大小、数目、包膜有无、癌栓有无、分化程度、HBsAg和肝硬变情况无关 ;HCC具有原发性耐药。     

Response of the isolated human seminiferous tubule to prostaglandins F1 alpha, F2 alpha, E1 and E2

In an attempt to ascertain whether prostaglandins alter the in vitro contractile activity of the human seminiferous tubule, the effects of prostaglandins on the isolated human seminiferous tubule were examined by recording the intratubular pressure with a servonull pressure with a servonull pressure measuring device. We describe here the first response of the human seminiferous tubule to prostaglandins. Prostaglandin F2 alpha (10(-9) M to 10(-6) M) produced contractions of the seminiferous tubules in a dose-dependent manner. In contrast, prostaglandins F1 alpha (10(-8) M to 10(-6) M), E1 (10(-9) M to 10(-6) M) and E2 (10(-8) M to 10(-6) M) produced relaxations of the seminiferous tubules which were dose dependent. The results from these experiments suggest that prostaglandins modulate the in vitro contractility of the human seminiferous tubules and thus may regulate the transport of spermatozoa and tubular fluid to the rete testis.     

Prolactin Promotes Hepatocellular Carcinoma through Janus Kinase 2

Background  

Hepatocelluar carcinoma (HCC) is one human cancer with obvious gender disparity. This study investigated the association of aberrant prolactin levels with HCC risk and the potential impacts on HCC of the prolactin receptor (PRLR)/Janus kinase 2 (JAK2) signaling.     

肝细胞肝癌中p27KIP1基因的表达及意义

目的 探讨p27^KIP1与原发性肝细胞癌(HCC)发生、发展的关系。方法 应用SASC(链霉 素亲和康—生物康复合物)免疫组化染色和mRNA原位杂交方法，对52例肝细胞肝癌中p27^KIP1蛋白和mRNA的表达进行了检测。结果 p27^KIP1基因的表达主要位于肝或肝癌细胞的细胞核中，呈纫颗粒状分布。p27^KIP1蛋白在癌旁肝组织中的阳性细胞指数为(10．7士7．6)％，明显高于癌组织的(1．5士o．9)％，并且p27^KIP1蛋白表达的阳性细胞指数与HCC细胞的分化程度呈正相关。p27^KIP1mRNA杂交阳性物呈蓝色纫颗粒状，主要位于肝或肝癌细胞的细胞核和细胞浆中，mRNA阳性的细胞分布更广泛，但在癌旁肝组织和不同分化程度的HCC组织中，p27^KIP1mRNA的阳性细胞指数差异无显著性意义。结论p27^KIP1蛋白与HCC的发生及细胞分级有关。     

Advanced Hepatocellular Carcinoma in a Patient with Type 1 Neurofibromatosis

The rare case is reported of advanced hepatocellular carcinoma (HCC) in a 50-year-old male with type 1 neurofibromatosis (NF 1). The patient presented in the surgical outpatient department with a 4-year history of multiple neurofibromas over the trunk and complaints of pain in the right upper abdomen for 4 months, progressive weight loss and loss of appetite. Investigation for both the abdominal complaints and the multiple neurofibromas led to the diagnosis of advanced HCC (according to the Barcelona Clinic Liver Cancer Sstaging and Treatment Strategy) with NF 1, and the patient is being managed on oral Sorafenib as palliative treatment. NF 1 occurs due to mutation in the NF 1 gene located on 17q, which codes for the protein neurofibromin, which has a tumor suppressor function. NF1 presents rarely with malignancy, in which case tumors of the central nervous system are the most common type. To the best of our knowledge this is only the second documented case of NF 1 presenting with HCC.     

Autotaxin Expression in Hepatocellular Carcinoma

ABSTRACT

Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. Despite the important progress observed in liver surgery, the survival rates are discouraging. The aim of this study was to investigate the expression of autotaxin in hepatocellular carcinoma. Materials and Methods: Liver tissues from 28 human hepatocellular carcinomas were evaluated for the expression of autotaxin by immunohistochemistry. The gender, age, histological grade, lymphovascular invasion, number of tumors, levels of serum alpha-fetoprotein (aFP), presence of liver cirrhosis, hepatitis, surgery and survival rates were recorded. Results: Immunohistochemistry confirmed the expression of autotaxin in hepatocellular carcinoma. The histological grade seems to be the only independent predictor of stronger autotaxin expression, as significantly higher levels of autotaxin were detected in histological grades II and III. In addition, levels of autotaxin seem to be the most important independent prognostic factor related to poor survival. There was an eight-fold higher risk of death in patients with high levels of autotaxin compared to patients with low levels. Conclusions: Autotaxin expression in hepatocellular carcinoma could be of great importance. High autotaxin expression in HCC is detected in patients with histological grade II and III. Further, patients with elevated expression levels were found to possess an eight-fold higher risk of death. Autotaxin role in HCC should be further elucidated.     

转录因子E2F1在非梗阻性无精症睾丸组织中的表达

目的旨在探讨E2F1核转录因子在人类睾丸组织中的表达与生精功能的关系。方法选取32例人类非梗阻性无精子症睾丸组织石蜡标本，采用HE染色观察曲细精管病理变化，同时用免疫组化SP法检测睾丸组织中核转录因子E2F1的表达;对照组选取13例人类正常睾丸组织。通过分析病理组HE染色，比较E2F1阳性染色范围及程度，评价E2F1核转录因子与生精功能的关系。结果非梗阻性无精子症睾丸组织HE染色显示精曲小管中无或仅少量精子，精曲小管的生精上皮脱落、排列紊乱，精曲小管壁部分有玻变、纤维变，生精细胞萎缩。32例非梗阻性无精子症睾丸组织中E2F1阳性表达8例，阴性表达24例，阳性率25%;13例正常睾丸组织中E2F1的阳性表达9例，阴性表达4例，阳性率69.23%;x2=7.694，差异有显著性（P〈0.01）。结论（1）E2F1核转录因子表达缺失与睾丸生精功能障碍密切相关;（2）非梗阻性无精子症睾丸组织精曲小管的生精上皮脱落、排列紊乱，生精阻滞。