乳腺癌组织内微血管分布的定量研究

用ＦⅧ相关抗原免疫组化染色定量观察４８例乳腺浸润癌。结果表明：有腋窝淋巴结转移组血管密度为每ｍｍ２１３５．４±４７．８个，无腋窝淋巴结转移组血管密度为每ｍｍ２９６．１±３１．４个，两组间的差异有显著意义（Ｐ＜０．０１）。同时血管的分布在癌组织旁每ｍｍ２１４２．４±４９．５个，在癌肿中央为每ｍｍ２９３．５±２８．６个，两组差异亦具有显著意义。结果揭示乳腺癌组织内血管生成与肿瘤的生长及腋窝淋巴结的转移关系密切。     

原发性肝癌组织中巨噬细胞与微血管的计数及其临床意义

目的: 研究原发性肝癌(primary hepatocarcinoma,PHC)组织中肿瘤相关巨噬细胞(tumor-associated macrophage,TAM)、微血管(microvessel,MV)的计数及其临床病理意义,并探讨二者之间的相互关系.方法: 应用ABC免疫组化法对47例PHC手术切除标本常规石蜡包埋切片分别检测MV和TAM并高倍镜下计数.结果: 47例PHC癌组织中MV与TAM计数均显著高于癌旁组织;MV(67.30±13.68)个/HP vs (37.20±10.58)个/HP (P<0.01); TAM(70.27±17.93)个/HP vs (44.15±9.10)个/HP (P<0.01).TAM与MV在术前AFU(α-岩藻糖) ≤10 μg/L病例的计数显著高于AFU>10 μg/L病例计数; TAM (74.13±18.33) 个/HP vs (61.15±13.54)个/HP (P<0.05); MV(70.41±13.03)个/HP vs (59.97±12.69)个/HP (P<0.05).伴转移病例癌组织中的MV计数(73.50±13.77)个/HP显著高于无转移病例(64.10±12.68)个/HP (P<0.05);TAM与MV在PHC中的计数与PHC的其他临床病理特征均无明显关系;癌组织中TAM计数与MV计数呈密切正相关(r=0.686,P<0.01).结论: TAM与MV计数与PHC的发生、进展关系密切;MV计数高的PHC易于发生浸润和转移;TAM与PHC的血管生成可能有着密切的关系.     

血管内皮生长因子-C表达、微血管及淋巴管密度与原发性肝细胞癌临床病理特征的关系

原发性肝细胞癌是常见的恶性肿瘤.肝癌的发生、发展、浸润、转移与其脉管系统(包括微血管、微淋巴管)密切相关[1].     

Macrophage migration inhibitory factor promotes intestinal tumorigenesis

BACKGROUND & AIMS: The cytokine macrophage migration inhibitory factor (MIF) is expressed throughout the human gastrointestinal tract. Recently, protumorigenic activity of MIF has been described in several cancer models. Therefore, we investigated the expression and function of MIF during the early stages of intestinal tumorigenesis. METHODS: MIF messenger RNA, protein, and tautomerase activity were measured in normal intestinal mucosa and adenomas from patients with sporadic colorectal adenomas and in the adenomatous polyposis coli (Apc)Min/+ mouse model of intestinal tumorigenesis. MIF function was investigated by using VACO-235 human colorectal adenoma cells in vitro and by testing the effect of genetic deletion of Mif on ApcMin/+ mouse intestinal tumorigenesis. RESULTS: MIF expression and tautomerase activity were increased in human and ApcMin/+ mouse intestinal adenomas compared with adjacent normal mucosa. Up-regulation of MIF occurred mainly in epithelial cells (associated with an increasing grade of dysplasia), but also in stromal plasma cells. Exogenous MIF inhibited apoptosis and promoted anchorage-independent growth of VACO-235 cells (maximal at 100 ng/mL). Homozygous deletion of Mif was associated with a reduction in the number and size of ApcMin/+ mouse adenomas (P = .025 for the difference in large [>7-mm] tumors) and decreased angiogenesis (43% decrease in mean tumor microvessel density), but there was no alteration in epithelial cell apoptosis or proliferation. CONCLUSIONS: MIF expression is increased in sporadic human colorectal adenomas, and exogenous MIF drives tumorigenic behavior of epithelial cells in vitro. Mif also promotes intestinal tumorigenesis (predominantly via angiogenesis) in the ApcMin/+ mouse. Therefore, MIF is a potential colorectal cancer chemoprevention target.     

肝细胞肝癌微血管密度与雌激素受体表达的临床病理意义

研究肝细胞肝癌(Hepatocellular Carcinoma,HCC)微血管密度(Microvessel Density,MVD)与雌激素受体(Estrogen Receptor,ER)表达之间的关系,以及此二者与临床病理学特征之间的关系.36例HCC的患者分为ER(+)组和ER(-)组.按MVD值分为MVD＜中位值组和MVD＞中位值组,比较各组有预后意义的临床病理学参数之间的差别.ER(+)14例,ER(-)22例.全组MVD自3至121(44.67±32.15中位值为36).ER(+)的HCC为直径较小、多有完整的包膜和较低的血清AFP浓度.MVD较低的HCC多为单结节、直径较小、细胞分化较好、血清AFP浓度较低.ER含量与MVD呈负相关.由此可见(1)ER(+)或MVD较低的HCC分别比ER(-)或MVD较高的HCC恶性度较低.(2)ER与MVD均是有价值的预后指标.     

Tumour angiogenesis and c-Met pathway activation – implications in breast cancer

Breast cancer is a heterogeneous disease with wide range of clinical behaviour. Tumour angiogenesis and metastasis have been considered as prognostic markers of the breast carcinoma, and c-Met, a transmembrane receptor tyrosine kinase has been implicated in both these processes of tumour progression. This study was conducted to elucidate c-Met and downstream signalling pathways in breast cancer and correlate with angiogenesis as assessed by microvessel density (MVD) and other prognostic parameters including lymph node metastases. Microvessel density (MVD) was assessed by endothelial cell (CD34) marker in breast cancers. c-Met was evaluated by immunohistochemistry for protein expression and by copy number assay for amplification at gene level. PCR array for gene expression related to c-Met, RAS-MAPK, PI3K-AKT and angiogenesis pathway was performed by real-time PCR. c-Met protein, copy number and mRNA expression did not differ significantly with the lymph node status or MVD. However, Her-2 overexpressing group showed c-Met protein overexpression and amplification. c-Met protein overexpression was also noted in the Luminal B subtype though no amplification was noted. Thus, the c-Met immunohistochemistry score and the c-MET copy numbers did not correlate with each other. c-Met downstream pathway genes (RAS-MAPK, PI3K-AKT and angiogenesis pathway) showed significant upregulation in Luminal B molecular subtype, lymph node-positive cases and cases with high MVD. The downstream signalling pathways (angiogenesis, RAS-MAPK and PI3K-AKT) were associated high MVD, lymph node metastases, and Her-2 and Luminal B subtype. Since inhibitors of these pathways are commercially available, these can be of therapeutic significance.     

Increased angiogenesis in bone marrow of children with acute lymphoblastic leukaemia has no prognostic significance

The importance of angiogenesis for the growth and viability of solid tumours has been established. Similarly, prognostic information may be gained from the extent of angiogenesis in these tumours. Haematopoietic malignancies should have equal requirements for angiogenesis and important prognostic information may be derived from quantification of bone marrow angiogenic activity. We retrospectively investigated 82 bone marrow trephine biopsies from 41 children with acute lymphoblastic leukaemia (ALL) at diagnosis and following treatment. Nine normal bone marrow trephines from age-matched children were also analysed as controls. The microvessels were stained immunohistochemically with anti-Factor VIII-related antigen (antivWF) and antithrombomodulin (anti-THR). Angiogenesis was quantified manually by two independent observers and was highly reproducible (Pearson's r = 0.91). Staining with anti-vWF and anti-THR was highly specific for microvessels and thetwo stains closely correlated (r = 0.68). Microvessel densities (MVD) at presentation were significantly increased in the majority of patients in comparison with controls (P < 0.0001) and MVD dropped towards normal in remission (P < 0.0001). Of interest, the difference in total vessel counts between leukaemic and normal/remission marrows was contributed solely by small microvessels. There was no significant difference in MVD at presentation or remission from children in poor prognostic groups or those who subsequently relapsed. Similarly, we could not find an association with age, sex, cytogenetic abnormality or disease phenotype.     

兔VX2肝癌超声造影定量指标与肿瘤微血管密度及血管内皮生长因子的相关性分析

目的研究肝癌超声造影定量指标与肿瘤微血管密度（MVD）及血管内皮生长因子（VEGF）的相关性。方法25只VX2成年兔肝癌模型,兔龄3个月,体质量（2．9±0．1）kg。行超声造影检查,利用Qkab软件对造影动态图像进行时间-强度分析,得出肝癌组织与周边正常肝组织曲线增强上升斜率（AS）、开始增强时间（AT）、达峰时间（TTP）、峰值强度（PI）、曲线下面积（AUC）及相对参数,造影后对标本做MVD和VEGF检测,分析超声造影各定量指标与肝癌组织内部MVD及VEGF的相关性。结果在超声造影定量指标中,肝癌组织的AT、TTP及PI与周边正常肝组织相比[（7．29±0．73）svs（10．15±0．44）s,（10．02±0．73）s vs（17．01±0．81）S,24．24±4．29YS16．83±1．511,差异有显著统计学意义（P〈0．01）。肝癌组织的各项定量指标中,相对TTP与MVD、VEGF呈正相关（r分别为0．517、0．528,P〈0．05）,相对PI与MVD呈正相关（r=0．564,P〈0．01）。MVD与VEGF表达呈正相关,相关系数为0．641（P=0．01）。结论超声造影定量指标可在一定程度上反映肝癌组织内部微血管分布情况。有一定临床实用价值。     

Expression of various multidrug resistance-associated protein (MRP) homologues in brain microvessel endothelial cells

Multidrug resistance-associated protein (MRP) actively transports a broad range of anionic compounds out of the cell. To date, six different homologues of MRP (i.e. MRP1-MRP6) have been identified. The current study examines the expression of the various MRP homologues in both primary cultured bovine brain microvessel endothelial cells (BBMEC) and the capillary-enriched fraction from bovine brain homogenates. RT-PCR analysis demonstrated the presence of MRP1, MRP4, MRP5 and MRP6 in both BBMEC and the capillary-enriched fractions of brain homogenates. While low levels of MRP3 were detected in the BBMEC, it was not observed in the capillary-enriched fraction. In addition, RT-PCR and Western blot studies indicated an absence of MRP2 expression in both blood-brain barrier preparations. The presence of several different MRP homologues in the brain microvessel endothelial cells may be important in controlling the permeability of the blood-brain barrier to organic anions.