Prox-1与淋巴管新生和肿瘤转移的关系

侵袭和转移是恶性肿瘤的重要生物学行为之一,淋巴道转移是恶性肿瘤难以根治以及高病死率的主要原因,也是判断患者预后的主要指标。果蝇prospero同源异形盒蛋白1（prospero homeobox protein 1,Prox-1）在胚胎时期淋巴管形成过程中具有重要作用,可以作为淋巴管内皮细胞标志物,显示肿瘤新生淋巴管,并与肿瘤淋巴道转移密切相关。尽管Prox-1促进胚胎淋巴管形成机制的研究较为深入,但是在肿瘤淋巴管新生和淋巴道转移的作用机制方面仍有待于进一步探讨,Prox-1可能作为抑制肿瘤淋巴管新生和治疗肿瘤的新靶点,用于阻断肿瘤转移和改善患者预后。现就Prox-1与胚胎淋巴管形成、肿瘤淋巴管新生以及与肿瘤淋巴道转移关系的相关研究现状综述如下。     

肿瘤淋巴管形成与肿瘤转移关系的研究进展

恶性肿瘤是严重危害人类健康的常见疾病 ,造成恶性肿瘤治疗困难的主要原因之一是恶性肿瘤常发生远处部位的转移。如果肿瘤只局限在原发部位 ,则通过手术等方法可使患者治愈 ,转移是肿瘤患者死亡的主要原因。肿瘤发生播散和转移的途径主要有 :(1)局部浸润 ,体腔、体表种植 ;(2 )通过血管的血行转移 ;(3)通过淋巴管的淋巴转移等。其中通过淋巴管常常是某些肿瘤初始转移阶段的最主要途径 ,肿瘤细胞进入引流淋巴结 ,继而再进入血流 ,造成更广泛的远处转移 ,威胁患者的生命。在过去的 10余年中 ,肿瘤新生血管的研究成为肿瘤研究的一个热点。自 19…     

肿瘤转移相关蛋白1在小鼠肝癌诱发过程中的表达与意义

目的:建立BALB/c小鼠肝癌动物模型,观察分析肿瘤转移相关蛋白1(MTA1)在建模过程中表达的变化及可能的意义。方法:采用联合二乙基亚硝胺(DEN)/四氯化碳(CCl4)/乙醇的方法诱导正常成年BALB/c雄性小鼠150 d,HE染色观察小鼠肝脏病变情况,免疫组化染色观察MTA1在肝脏病变部位的表达情况。结果:实验组小鼠肝脏镜下依次出现炎症、纤维化和肿瘤性改变。在肝脏病变进展的进程中,MTA1的表达量增加;且肝硬化期,MTA1主要在胞质中表达。结论:MTA1在DEN诱发小鼠肝肿瘤过程中表达量增加、表达位置改变,提示MTA1可能在肝脏肿瘤形成的全程均具有重要作用。     

肿瘤转移相关蛋白1表达的降低在银屑病发病中的可能作用

目的:探讨肿瘤转移相关蛋白1在银屑病发生发展过程中的作用及其临床价值.方法:免疫组化方法检测36例银屑病组织和12例正常皮肤组织中肿瘤转移相关蛋白1(MTAI)的表达水平;并分析MTAI与银屑病临床病理特征的关系以及两者之间的相关性.结果:银屑病中MTAI蛋白表达阳性率为22.2% (8/36),明显低于正常皮肤组织(100%,P＜0.05).结论:结果提示MTAI的表达与银屑病密切相关,提示MTA1表达的降低可能是银屑病发展中的一个关键步骤.     

人直肠癌组织淋巴管的微细分布

目的研究人直肠癌淋巴管的微细分布和结构特征,为进一步探讨癌组织的淋巴道转移机理提供形态学依据。方法取直肠癌手术切除的组织,按不同部位取材,812树脂包埋,半薄切片光镜观察淋巴管的形态及结构特征。结果在癌中心区未见淋巴管,癌周围区的淋巴管密度较正常区增多,直肠癌周边区淋巴管的体密度和数密度均明显高于正常区(P<0.05,P<0.01)且管腔扩张,管壁常见到溶解、破坏,并见癌细胞团靠近扩张的毛细淋巴管。结论癌周围区的淋巴管有数量及形态结构的改变,增加了癌细胞淋巴道转移的机会。直肠癌的淋巴道转移可能以溶解、破坏淋巴管壁而进入淋巴管为主要途径。     

肿瘤淋巴管与肿瘤转移的研究进展

肿瘤细胞浸润淋巴管并发生淋巴结转移是导致肿瘤患者死亡的主要原因。研究表明,肿瘤中存在结构和分布异常的淋巴管,其生成与肿瘤细胞产生的细胞因子（如VEGF-C、Cox-2）有关。目前,随着特异性的淋巴内皮的标记物VEG—FR-3、LYVE-1、podoplanin、D2-40等的发现,肿瘤淋巴管已成为当前研究热点。笔者就近来有关肿瘤淋巴管和肿瘤转移的研究进展综述如下。[第一段]     

肿瘤淋巴管生成与淋巴道转移的相关研究进展

在肿瘤转移机制的研究中,有关淋巴管生成与肿瘤转移关系的研究近年来已逐渐成为热点,肿瘤淋巴系统作为肿瘤尤其是实体瘤转移的重要通道的研究意义也不断被认识。临床病理学研究显示实体瘤播散的最早途径是经淋巴道的区域性淋巴结播散,但目前对此转移途径的相关研究仍处于比较基础的阶段,不像对肿瘤血管系统的研究那样广泛和深入。现就肿瘤淋巴管生成与淋巴道转移的研究现状作一简要综述。     

肿瘤淋巴管生成与肿瘤转移研究进展

现已证实淋巴管是肿瘤细胞转移播散至局部淋巴结的主要通路。但关于淋巴管发生的分子机制却了解甚少。新近研究证明血管内皮生长因子(VEGF)-C和VEGF-D及其受体VEGFR-3信号通路是淋巴管形成的基础,并在转基因动物模型观察到VEGF-C和VEGF-D可诱导肿瘤淋巴管生成,并促进其淋巴结转移。然而,VEGF-C和-D如何调节肿瘤相关淋巴管生成,对于肿瘤细胞如何从原发肿瘤逃逸,并怎样进入淋巴管,目前仍不清楚。为此,现就近期淋巴管生成与肿瘤转移研究进展作一简要综述。     

结肠直肠癌cyclin D1及p16蛋白表达与预后的关系

我们应用ＳＰ方法检测结肠直肠癌ｃｙｃｌｉｎＤ１、ｐ１６蛋白的表达情况,探讨二者与肿瘤临床、病理因素及预后关系。一、材料与方法１．标本：８９例石蜡组织取自１９９１～１９９４年期间本院结、直肠腺癌手术切除标本,并进行术后３～６年的随访。其中高分化腺癌３０例,中分化腺癌４４例,低分化腺癌１５例。按Ｄｕｋｅｓ临床分期,无Ａ期病例,Ｂ期４２例,Ｃ期３７例,Ｄ期１０例。正常结肠直肠粘膜为纤维结肠镜及病理检查未发现明显异常的结肠直肠粘膜活检标本共１２例。２．免疫组化染色：采用ＳＰ法,鼠抗ｃｙｃｌｉｎＤ１（ＨＤ…     

结直肠癌中TGF-β1表达与肿瘤浸润转移和血管形成的关系

目的　探讨结直肠癌中转化生长因子 β1(TGF β1)的表达与肿瘤浸润转移和血管形成的关系。 方法　免疫组化S P法检测 12 6例结直肠癌中TGF β1和血管内皮生长因子 (VEGF)的表达 ,同时应用CD34标记肿瘤间质中微血管密度 (MVD)。结果　 12 6例结直肠癌中TGF β1和VEGF的阳性表达率分别为 4 2 1%和 6 3 5 %。结直肠癌中TGF β1、VEGF蛋白的表达和MVD与肿瘤的浸润深度、淋巴结转移和Dukes分期呈正相关 (P <0 0 5 ) ;VEGF在TGF β1表达阳性的结直肠癌中的阳性表达率高于TGF β1表达阴性的结直肠癌 (P <0 0 5 ) ,TGF β1表达阳性的结直肠癌MVD高于TGF β1表达阴性的结直肠癌(P <0 0 5 )。结论　TGF β1可能通过间接或直接刺激肿瘤血管形成而促进结直肠癌的浸润转移     

大肠肿瘤中Tiam1的表达及临床意义

目的探讨T淋巴瘤侵袭转移诱导因子1(T lymphom a invasion and m etastasis induc ing factor 1,Tiam1)表达与大肠癌发生、发展和转移的关系。方法应用免疫组化方法检测大肠正常组织、大肠腺瘤、大肠癌和大肠淋巴结转移癌石蜡组织标本中Tiam1蛋白的表达情况。应用RT-PCR和免疫组化方法检测大肠癌细胞株中Tiam1 mRNA和蛋白的表达情况。结果Tiam1蛋白在大肠正常组织、腺瘤、癌及淋巴结转移癌中表达差异有显著性(2χ=23.561,P<0.01);两两比较发现,腺瘤Tiam1表达比大肠正常组织高(Z=-2.423,P<0.05),淋巴结转移癌组织Tiam1表达比大肠癌组织高(Z=-2.051,P<0.05),而大肠癌组织与腺瘤组织Tiam1表达差异无显著性(Z=-0.938,P>0.05)。在大肠癌组织中,伴发转移的大肠癌组织比未发生转移的大肠癌组织Tiam1表达明显增强,差异具有显著性(Z=-3.176,P<0.01)。RT-PCR结果显示Tiam1基因在高转移的LoVo和SW 620中呈高表达,在低转移的LS174T和HT29中呈低或不表达,在SW 480、HCT116等呈中度表达。结论Tiam1表达与大肠癌转移存在密切关系,Tiam1表达可作为大肠癌转移过程中一个有价值的指标。     

Clusterin expression is associated with decreased disease‐free survival of patients with colorectal carcinomas

Redondo M, Rodrigo I, Alcaide J, Tellez T, Roldan M J, Funez R, Diaz‐Martin A, Rueda A & Jiménez E
(2010) Histopathology 56, 932–936
Clusterin expression is associated with decreased disease‐free survival of patients with colorectal carcinomas Aims: It has been demonstrated that increased clusterin expression is involved in malignant progression and that anticlusterin treatment leads to selective apoptosis. The aim of this study was to determine the clinicopathological significance of clusterin expression in human colorectal carcinomas. Methods and results: The expression of clusterin was examined in 31 adenomas and 103 colorectal carcinomas. Normal epithelial cells were always negative for clusterin expression, but clusterin expression was present in 16% (5/31) of adenomas and this percentage increased in colorectal carcinomas (30%, 31/103). Immunopositivity always presented an apical cytoplasmic pattern. The expression level of clusterin did not correlate with age, gender, grade or stage. However, its expression was significantly associated with a decrease in disease‐free survival (P < 0.05). In a multivariate Cox proportional hazards model, clusterin expression remained a significant independent predictor. Conclusions: Clusterin expression may have a role in colonic carcinogenesis and may help identify patients with more aggressive tumours who may benefit from targeted therapy.     

Expression of MTA2 and Ki-67 in hepatocellular carcinoma and their correlation with prognosis

The aim of this study was to investigate the relationship among MTA2, Ki-67 and HCC patient prognosis. Tissue microarray and immunohistochemistry were used to detect the expression of MTA2 and Ki-67 in HCC samples and corresponding adjacent samples. We found MTA2 and Ki-67 were both increased in HCC tissues than those in adjacent tissues and nuclear MTA2 was associated with Ki-67 (P = 0.019). Moreover, nuclear MTA2 was a risk factor of distant metastasis in patients with HCC andKi-67 showed a negative correlation with histological grade (P < 0.05, P < 0.01, respectively). Multivariate Cox model analysis revealed that Ki-67 expression was an independent prognosis factor in HCC patients (P = 0.020). These results indicated there might be a tight correlation among MTA2, Ki-67 and HCC prognosis. MTA2 combined with Ki-67 might be used to predict HCC patient prognosis.     

VEGF-A和C在人结肠癌淋巴管生成和淋巴道转移中的作用

目的分析血管内皮生长因子(VEGF)-A和VEGF-C在人结肠癌组织的表达及与结肠癌淋巴管生成和淋巴道转移的关系。方法取人结肠癌组织91例,应用免疫组化方法检测VEGF-A和VEGF-C在结肠癌组织中的表达。应用D2-40标记结肠癌组织的淋巴管,观察结肠癌组织的淋巴管生成情况。结果结肠癌组织中VEGF-A和VEGF-C的表达水平明显高于正常组织,VEGF-A和VEGF-C表达阳性的结肠癌组织的淋巴管密度(LVD)明显高于阴性组织,VEGF-A和VEGF-C的表达及LVD均与淋巴结转移及Duke's分期相关。结论结肠癌组织VEGF-A和VEGF-C过表达与结肠癌的淋巴管生成和淋巴道转移相关。     

Metastasis-associated protein 1 (MTA1) in gastric cancer tissues is positively associated with poorer prognosis

Background

The present study examined the clinical significance of metastasis-associated protein 1 (MTA1) in the progression and patient survival of gastric cancer.

Expression and distribution of insulin-like growth factor-1 receptor in human carcinomas

The insulin-like growth factor-1 receptor (IGF1-R) is a cellular receptor overexpressed in many tumor cell lines and in some human tumors that seems to play a critical role in transformation, tumorigenicity, and metastasis. To date, a comprehensive evaluation of tissue distribution of IGF1-R in human carcinomas from different anatomical sites has been lacking. Using stage-oriented human cancer tissue microarrays, we studied IGF1-R expression and distribution in a group of 152 human carcinomas from a variety of anatomical sites and from 63 normal tissues through immunohistochemistry. The tumors included carcinomas from breast (8), ovary (9), endometrium (7), esophagus (5), stomach (7), pancreas (7), liver (4), colon (10), kidney (14), bladder (17), prostate (11), head and neck (31), salivary glands (8), lung (13), and skin (1). Formalin-fixed, paraffin embedded tissues of each case were immuno-stained using the avidin-biotin peroxidase method and an anti-IGF1-R rabbit polyclonal antibody. High-membranous IGF1-R staining was observed in 7 of 8 (87.5%) breast carcinomas, in 9 of 9 (100%) ovarian carcinomas, in 7 of 7 (100%) endometrial carcinomas, in 5 of 7 (71.1%) gastric carcinomas, in 4 of 7 (57.1%) pancreatic carcinomas, in 9 of 10 (90%) colon adenocarcinomas, in 11 of 13 (84.6%) lung carcinomas, in 6 of 11 (54.5%) prostatic adenocarcinomas, and in 17 of 17 (100%) transitional cell carcinomas of the bladder. Only a minority of squamous cell carcinomas of the head and neck and esophagus (34), salivary gland tumors (5), and renal cell carcinomas (14) were IGF1-R positive. This study demonstrates the overexpression of IGF1-R across a wide variety of human carcinomas of glandular or transitional cell origin.     

非小细胞肺癌中Abi1的表达及其与预后的关系

目的:探讨Abi1在人非小细胞肺癌(NSCLC)组织中表达的临床意义及其与肺癌转移和预后的关系。方法:采用RT-PCR检测41例肺癌及其对应癌旁组织Abi1 mRNA的表达;免疫组织化学检测112例人NSCLC石蜡切片中的表达,采用x~2检验检测其与临床病理学特征的关系,Log-rank检验Abi1表达与生存时间的关系,Cox模型作单因素和多因素预后分析。结果:41例肺癌中Abi1 mRNA的表达较癌旁肺组织高,光密度比值分别为1.9±1.0和1.0±0.6,差异有显著性;肺癌Abi1 mRNA的过表达与肺癌的分期、血管浸润、淋巴结转移有关。免疫组织化学染色证实Abi1主要表达在癌细胞胞质,Abi1阳性表达患者生存率明显低于阴性组。结论:Abi1与肺癌的侵袭转移关系密切并有可能成为新的预后指标。     

大肠癌PARP表达与P-selectin和ICAM-1表达的相关性

目的初步探讨聚腺苷二磷酸核糖聚合酶(PARP)与大肠癌侵袭转移的关系及其可能机制。方法采用SP免疫组化法检测PAR(聚腺苷二磷酸核糖,系PARP产物)、P-selectin及ICAM-1的表达;并应用免疫荧光双标法检测PAR与P-selectin、ICAM-1的共表达。结果大肠癌组织内PAR、P-selectin及ICAM-1的表达均明显高于对照肠黏膜(P<0.05);3种蛋白的表达仅与大肠癌转移有关(P<0.05),而与其他临床病理因素无关;PAR与P-selectin和ICAM-1的表达均呈正相关关系(P<0.05)。结论大肠癌组织内PARP活性增强,并可能通过上调P-selectin和ICAM-1的表达而有利于大肠癌侵袭转移,有望成为判断大肠癌转移的参考指标之一。     

Increased expression of Rab5A predicts metastasis and poor prognosis in colorectal cancer patients

Rab5A is reported to correlate with cancer development and progression. The purpose of this study is to explore the association between Rab5A expression and the clinical characteristics of colorectal cancer (CRC). Data containing three independent investigations from Oncomine database demonstrated that Rab5A is overexpression in CRC compared with normal tissue, similar result was also found in 32 matched CRC tissue samples by qPCR. The protein expression of Rab5A was examined in 390 CRC specimens and the results showed that high expression of Rab5A was significantly correlated with tumor size (P = 0.008), serum CEA (P = 0.002), liver metastasis (P = 0.014) and clinical stage (P = 0.010). Kaplan-Meier method suggested that overexpression of Rab5A protein expression had shorter overall survival times in CRC patients (P < 0.001). Multivariate Cox regression analysis confirmed Rab5A expression, tumor size and clinical stage as independent prognostic factor in CRC. In conclusion, the data indicated that higher expression of Rab5A was observed in CRC tissues and Rab5A may be identified as a useful predictor of metastasis and prognosis for CRC.