肿瘤微循环的新形式--血管生成拟态

血管生成拟态是在少数高度恶性肿瘤中新发现的一种血管生成方式,使得肿瘤极易侵袭和转移,其特征是管腔由癌细胞覆盖。血管生成拟态的发生与肿瘤细胞胚胎样特性、基质蛋白、金属基质蛋白酶等表达有关,血管生成拟态应与纤维血管隔、肿瘤内微出血等区别。     

不同微环境对黑色素瘤细胞侵袭能力和局部微循环模式形成的影响

目的明确不同微环境对肿瘤细胞侵袭能力和微循环模式的影响,并阐述其相关分子机制。方法将恶性黑色素瘤单细胞悬液B16分别接种至C57小鼠腹腔和后肢肌肉组织中,于接种肿瘤后第18天后处死动物,取腹腔内肿瘤组织和小鼠后肢肿瘤组织,免疫组织化学（sP法）CK18染色对后肢组和腹腔组肿瘤细胞恶性侵袭表型进行比较,并比较在不同微环境生长下肿瘤细胞缺氧诱导因子（HIF）．1仅的表达,免疫组织化学染色和RealtimePCR方法从蛋白水平和mRNA水平比较腹腔组和后肢组肿瘤细胞基质金属蛋白酶（MMP）-2和MMP-9的表达差别;并对肿瘤组织内不同微循环模式进行计数。结果免疫组织化学染色结果显示与腹腔组相比,后肢组肿瘤细胞CKl8、HIF-1仅表达明显增高（t=8．142,t=3．645,P均〈0．05）,同时也表达更高的肿瘤侵袭相关蛋白,肿瘤细胞表达MMP-2和MMP-9均明显高于腹腔组（t=4．916,t=7．782,P均〈0．05）,RealtimePCR检测结果也显示后肢组MMP-2和MMP-9mRNA表达也明显高于腹腔组（t=36．814,t=26．025,P均〈0．05）。在后肢组肿瘤组织中,血管生成拟态是肿瘤细胞获得营养的主要方式,而腹腔组肿瘤细胞获得营养供应方式主要通过内皮依赖性血管。结论不同生长微环境影响黑色素瘤细胞的恶性表型转化,致使肿瘤细胞分泌更多肿瘤侵袭转移相关蛋白,促进肿瘤细胞向周围组织浸润,肿瘤细胞侵袭能力的增高促进了肿瘤血管生成拟态的形成。     

肝细胞癌微循环与血供

肝细胞癌微循环与血供文／赵文龙，段积华１正常肝脏微循环及调节肝脏的微循环单位是肝小叶，它是由肝细胞围绕终末门静脉支、肝微动脉、胆小管、淋巴管及神经为轴心而组成的，亦是肝脏的功能单位。肝动脉血和门静脉血首先流入汇管区，并在汇管区带与肝窦充分混合，呈放射...     

血管内皮生长因子与肝细胞癌

血管内皮生长因子 (VEGF)具有促进内皮细胞增殖 ,加速新生血管形成及增加血管通透性等作用 ,在多血管型的肝细胞癌 (HCC)中起重要作用 ,包括肿瘤的生长、转移和复发 ,是判断HCC预后的良好指标。控制VEGF将有助于治疗HCC。     

CD133和CD34在肝细胞癌血管生成拟态形成中的表达及意义

背景：在恶性肿瘤中血管生成拟态的形成过程与肿瘤干细胞有密切联系。 目的：分析肝癌干细胞标志物CD133和CD34在肝细胞癌血管生成拟态形成中的表达及意义。 方法：建立肝癌细胞HCC97H、SMMC7721和正常肝细胞L02三维培养体系,结合激光捕获显微切割技术分离形成血管生成拟态的肝癌细胞,分别利用RT-PCR和Western blot技术检测CD133和CD34表达水平。 结果与结论：三维培养条件下,肝癌细胞HCC97H细胞形成血管生成拟态,肝癌细胞SMMC7721以及正常肝细胞L02未形成血管生成拟态。形成血管生成拟态的肝癌细胞HCC97H中CD133、CD34在mRNA及蛋白表达水平上均高于未形成血管生成拟态的肝癌细胞SMMC7721和正常肝细胞L02(P < 0.05)。表明高侵袭性肝癌细胞在三维培养下形成血管生成拟态,而低侵袭性肝癌细胞及正常肝细胞不能形成血管生成拟态;肝癌细胞形成血管生成拟态的过程中与表达肝癌干细胞有关。     

微循环概念的延伸及争议

近20年来 ,由于内皮细胞和血管生物学的研究发生了突破性进展 ,改变了过去内皮功能被动交换和血管“机械管道”调节血流的传统观念。现代生理学、药理学、蛋白组学、基因工程、影像诊断技术等不断创新 ,促进临床医学的迅速发展 ,微循环对于边缘学科的渗透 ,必将赋予新的内涵。本文就微循环概念的延伸 ,涉及微循环血管网络的解剖结构、生理功能和某些病理生理改变及其争议问题 ,复习文献进行综述性评价。1微血管网络解剖结构的基本概念动脉分支进入器官称微动脉(arteriole)。微动脉不断分支为1、2、3、4级微动脉(即A1、A2、A3、A4)。按解剖…     

syndecan-1表达对肝细胞癌增殖、血管生成和转移的影响

目的探讨syndecan-1在肝细胞癌（hepatocellular carcinoma,HCC）表达的临床病理意义,及其与肿瘤转移、增殖和血管生成的关系。方法用免疫组织化学染色检测了syndecan-1在30例HCC原发癌组织、癌旁组织和肝内转移灶的表达,血管内皮生长因子（vascularendothelial growth factor,VEGF）和CD34-微血管密度（microvessel density,MVD）在原发灶和肝内转移灶的表达,及Ki-67在原发灶的表达。结果与HCC癌旁组织相比,syndecan-1在原发癌组织表达水平明显增高,syndecan-1在肝内转移灶表达水平明显下降（χ2=25.62,P〈0.001）。在HCC原发癌组织中,syndecan-1表达强度与Ki-67指数呈正相关（r=0.386,P〈0.05）。在肝内转移灶中,syndecan-1表达强度与CD34-MVD呈正相关（r=0.370,P〈0.05）。结论 HCC组织syndecan-1表达可能影响肿瘤转移、增殖和血管生成,提示syndecan-1在HCC生长和转移中的特殊作用可能为HCC有效治疗策略提供新思路。     

肝细胞肝癌中LOXL2过表达与转移及预后的相关性

目的检测LOXL2和上皮-间质转化(epithelial-mesenchymal transition,EMT)相关基因在肝细胞肝癌组织中的表达,揭示LOXL2和EMT之间的关系,从而阐明LOXL2对肝细胞肝癌转移及预后的影响。方法采用免疫组化法检测106例肝细胞肝癌组织中LOXL2、Snail、E-cadherin和vimentin的表达,采用CD31/PAS双染法检测肝细胞肝癌中血管生成拟态(vasculogenic mimicry,VM)的情况,并分析LOXL2与EMT分子之间的相关性。采用χ~2和Spearman相关分析来分析其与VM形成和临床病理资料之间的关系。采用Kaplan-Meier法评估LOXL2对肝细胞肝癌患者生存时间的影响。采用Cox比例风险模型分析LOXL2对肝细胞肝癌预后的价值。结果 LOXL2表达与Snail、vimentin和E-cadherin的表达密切相关,LOXL2表达与肿瘤分级和VM形成相关。LOXL2阳性表达或VM形成的患者其总体生存期和无病生存期比LOXL2阴性表达和无VM形成的患者短(P0.05);同时具有LOXL2阳性表达和VM形成的患者预后最差。结论 LOXL2表达与EMT标记蛋白相关,并与肝细胞肝癌分级和VM形成密切相关,且对预后有一定的影响。     

原发性肝细胞癌的免疫标志物

原发性肝细胞癌是威胁人类生命健康的常见恶性肿瘤之一。肝细胞在长期诱癌因素的诱导下发生一系列改变,由肝细胞再生结节、低级别异型增生结节、高级别异型增生结节、早期肝细胞癌到进展期肝细胞癌。患者的预后及生存质量随着这一系列病变的发生、发展逐渐降低。因此,肝细胞癌的早期诊断显得尤为重要。但是由于这些病变的形态多样,具有一定的重叠,仅仅依靠形态学有时很难进行鉴别与诊断。临床工作中,有选择性的联合应用多种免疫标志物,可以有效提高肝细胞癌的检出率。本文将对Glypican-3、HepPar-1、AFP、CD34、Arg-1、CENPF、IMP-2和HSP 60等免疫标志物进行阐述,便于临床工作者选择性的进行组合,寻找个体化的组化Pannel。肝细胞癌术后复发率高是困扰医学界的难题之一。本文介绍了目前热门的相关免疫标志物,如SLeX、SUZ12、HP1BP3、CCR1、DCP。临床检测这些免疫标志物的表达情况,可以预测患者的预后情况,针对性的选择辅助治疗方法,提高患者的无瘤生存时间及生活质量。     

用图像分析仪对人肝细胞癌AgNORs的形态计量学研究

本研究采用图像分析仪对肝癌高发７０例人肝细胞（Ⅰ－Ⅳ级）测定以下四项指标参数：（１）细胞核面积，（２）ＡｇＮＯＲｓ银染颗粒计数；（３）银染颗粒面积；（４）比率。研究发现银染颗粒面积与癌细胞核面积呈正相关（Ｐ＜０．０００１）。不同分化的肝细胞癌各组之间及癌与正常肝组织之间ＡｇＮＯＲｓ各项参数均有明显差异（Ｐ＜０．００１）。并认为仅用人工目测银染颗粒计数是不全面的，应采用图像分析仪检测四项参数综合考虑     

Erythropoietin and erythropoietin receptor in hepatocellular carcinoma: correlation with vasculogenic mimicry and poor prognosis

To evaluate erythropoietin (Epo) and erythropoietin receptor (EpoR) expression, its relationship with vasculogenic mimicry (VM) and its prognostic value in human hepatocellular carcinoma (HCC), we examined Epo/EpoR expression and VM formation using immunohistochemistry and CD31/PAS (periodic acid-Schiff) double staining on 92 HCC specimens. The correlation between Epo/EpoR expression and VM formation was analyzed using two-tailed Chi-square test and Spearman correlation analysis. Survival curves were generated using Kaplan-Meier method. Multivariate analysis was performed using Cox regression model to assess the prognostic values. Results showed positive correlation between Epo/EpoR expression and VM formation (P < 0.05). Patients with Epo or EpoR expression exhibited poorer overall survival (OS) than Epo-negative or EpoR-negative patients (P < 0.05). Epo-positive/VM-positive and EpoR-positive/VM-positive patients had the worst OS (P < 0.05). In multivariate survival analysis, age, Epo and EpoR were independent prognostic factors related to OS. These results will provide evidence for further research on HCC microcirculation patterns and also will provide new possible targets for HCC diagnosis and treatment.     

Growth patterns and interstitial invasion of small hepatocellular carcinoma

Twenty-five caw of small hepatocellular carcinoma (HCC; dhmeter ≥30mm) were evaluated for overall morphologic features and growth patterns. The tumors often showed a uelldtfferentlated, normotrabecular histologic pattern and insidious interstitial invasion, which resembled benign hepetocytes scattered in connective tissues. As the tumor grew, B less-differentiated tumor area became predominant. Portal tracts Included in small HCC nodules were quantitatively assessed, revealing that they progressively reduced in number with tumor growth. The tumor margin was often reported to be unclear. The present results indicate that the histologk grade of tumor differentiation, capsular formation, existence of liver cirrhosis and patterns of interstitial invaslon are important factors for determining the nature of the margin. The score of argyrophilic nuclear organizer regions (AgNOR) was examined in 5 cases showing typical interstitial imaslon with the insidious type. In each case, the AgNOR score of the invading tumor cells was lower than that of turnor cells within the HCC nodules, but higher than benign hepatocytes in cirrhotic parenchyma. It clarified that the growth activity of well-differentiated HCC was rather suppressed upon their interstitial invasion.     

肝细胞癌细胞外基质的分布形式及其临床意义

目的：了解细胞外基质在肝细胞癌的分布形式；探讨其与肝细胞癌恶性程度的关系。方法：用５种细胞外基质抗体对４０例肝细胞癌作免疫组化染色。结果：显示４种分布形式：连续梁周腺泡型、断续梁周腺泡周型、血管间质型、胞膜胞浆型。前３型与肿瘤生长方式、细胞分化和增殖密切相关。结论：提示细胞外基质在评价肝细胞癌的恶性程度是有用的标志物。     

microRNA与肝癌

肝癌是世界上最常见的恶性肿瘤之一,其发病率和病死率极高。microRNA(miRNA)是一类单链的非编码RNA,通常在转录后水平调控基因的表达。最近多项研究表明miRNA在肝癌中发挥着重要作用,已经成为肝癌诊断、治疗中的一个靶标。     

Notch信号通路与肝癌的研究进展

Notch信号通路是一种高度保守的信号通路,在调节细胞分化、增殖和凋亡等一系列生理病理过程中都起着关键性的作用。Notch信号在肝癌中频繁发生异常表达及激活突变,其通过多种机制促进肝癌的发生发展,且与肝癌的侵袭、转移和预后密切相关。因此,Notch信号可作为肝癌治疗的一个靶标,为肝癌的治疗提供新的方向和机遇。     

Clinicopathologic study on clear cell hepatocellular carcinoma

In order to study the clinicopathologic characteristics of the clear cell variant of hepatocellular carcinoma (HCC), 215 consecutive cases measuring less than 5 cm in diameter were reviewed. The cases were divided into clear cell HCC (20 cases); focal clear cell HCC (77 cases); and non-clear cell HCC (118 cases). Clinical and pathological findings were compared among these groups. Clear cell HCC was moderately differentiated in 80% of cases and the incidence was not related to tumor size. The male to female ratio was 2.3:1, lower than the 6.9:1 of non-clear cell HCC. The association rate with liver cirrhosis was 90%, higher than the 59.3% of non-clear cell HCC. Three- and five-year survival rates, and no recurrence time were 54.5%, 33.3%, and 564 days, respectively, lower than the findings of 74.3%, 46.1%, and 770 days for non-clear cell HCC. But there is no significant difference in prognosis between both groups. Ultrastructurally, clear cells showed abundant glycogen storage and a variable degree of fat vacuoles, with a marked reduction of the number and size of organelles in the 8 cases examined. Non-clear cells of focal clear cell and non-clear cell HCC showed a moderate degree of glycogen storage in 85.7% and 28.6% of the seven cases examined from each group, with significant difference. It was concluded that clear cell HCC occurs mostly in the moderately differentiated form and is characterized by high female prevalence, high rate of association with liver cirrhosis, and has no significant difference in prognosis compared with non-clear cell HCC.