人胰腺癌组织LYVE-1表达与癌组织淋巴管转移关系研究

目的观察胰腺癌组织淋巴管内皮细胞LYVE-1的表达,为研究癌淋巴管转移的分子机制提供形态学依据。方法用免疫组化的方法对人胰腺癌和正常胰腺组织中LYVE-1的表达情况进行观察,用LYVE-1来标记淋巴管,检测癌组织中微淋巴管密度（LMVD）。结果胰腺癌组织血管内皮细胞LYVE-1不染色,淋巴管内皮细胞LYVE-1阳性表达,经计数微淋巴管数量,癌组织中的LMVD明显高于癌旁正常胰腺组织（P〈0.01）,并且LMVD的表达与VEGF-C、VEGF-D的表达具有显著相关性（P〈0.01）。结论LYVE-1可选择性的表达在胰腺癌组织淋巴管内皮上,能明确的区分血管及淋巴管成分,可作为一个淋巴管内皮细胞较特异的标记物。由于LMVD在癌组织中的表达明显增高,说明淋巴管数量的增加可能与胰腺癌的淋巴转移有关。     

Lymphangiogenesis Occurring in Transplanted Corneas

Immunological rejection is the major cause ofcorneal allograft failure .Corneal newblood vessels(hemangiogenesis) and lymphatic vessels (lym-phangiogenesis) are well-known high-risk factorsin corneal transplantation. Although i mmunosup-pressive-agents have been used systematically andlocally ,survival rate of corneal grafts placed intovascularized recipient beds is only 51 %[1].In con-trast to the studies with respect to processes ofblood vessel proliferation,the reports on corneallymphangiog…     

VEGFR-3、LYVE-1在胃癌中的表达研究

目的比较VEGFR-3、LYVE-1在胃癌组织中的表达,选择较为可靠的淋巴管内皮标志物。方法利用免疫组织化学方法检测CD34、VEGFR-3和LYVE-1在53例胃癌组织及正常胃粘膜组织中的表达,并进行微淋巴管密度（lymphatic vessel density,MLD）及微血管密度（microvessel density,MVD）计数;与公认的血管内皮标志物CD34作比较,评价VEGFR-3和LYVE-1两种淋巴管内皮标志物的表达情况。结果 CD34和VEGFR-3阳性脉管密度具有相关性（r=0.387,P=0.003）;而LYVE-1与CD34阳性管数不相关（r=-0.181,P=0.232）,表明VEGFR-3阳性管多数是血管,LY-VE-1阳性管多数是淋巴管而极少数是血管,提示LYVE-1是较为特异的淋巴管内皮标志物。结论 LYVE-1是较为特异的淋巴管内皮标志物,肿瘤瘤周淋巴管生成可能促进了淋巴结转移的发生。     

人直肠癌淋巴管生成相关因子与癌转移关系的探讨

目的 探讨血管内皮生长因子C在直肠腺癌淋巴管生成中的作用。方法 用免疫组化SABC染色法观察63例直肠腺癌组织中VEGF-C和淋巴管内皮透明质酸受体1蛋白表达的情况。结果 直肠腺癌组织周边部淋巴管密度比内部明显增高（P〈0．01）；直肠腺癌组织周边部VEGF-C阳性细胞数比内部明显增多（P〈0．01）。VEGF-C表达阳性细胞密度和淋巴管密度呈正相关；直肠腺癌组织中VEGF-C异位表达在淋巴管内皮细胞上，而在血管中未见表达，差异有显著性（P〈0．01）。结论 VEGF-C促进直肠腺癌淋巴管的病理生成，淋巴管生成提示在为肿瘤细胞提供养分的同时，也为肿瘤转移创造了条件。     

血管内皮生长因子C与肿瘤转移的研究

恶性肿瘤的转移依赖于新生血管和淋巴管的形成。血管内皮生长因子C(VEGF-C)是一种特异性血管、淋巴管内皮细胞调节因子,能与受体VEGFR-2和VEGFR-3结合从而促进血管和淋巴管生长。近年来的研究表明,VEGF-C能促进多种恶性肿瘤的侵袭和转移。现对VEGF-C的结构、功能,及其与在恶性肿瘤、血道转移、淋巴道转移中的可能机制进行综述。     

VEGF-C介导的乳腺癌肿瘤淋巴管生成及定位

目的：探讨血管内皮生长因子C（vascular endothelial growth factor C，VEGF-C）介导的乳腺癌肿瘤淋巴管生成及定位。方法：分子生物学原位杂交方法检测VEGF-C mRNA基因在89例原发性乳腺癌组织中的表达；免疫组化SP法对乳腺癌肿瘤淋巴管进行血管内皮生长因子受体3（vascular endothelial growth factor receptor-3，VEG-FR-3）标记。结果：在89例原发性乳腺癌组织中，49例表达VEGF-C mRNA，表达率为55．06％。VEGF-C mRNA的表达与乳腺癌淋巴管密度（lymphatic vessel density，LVD）和腋淋巴结转移呈正相关；与VEGF-CmRNA阴性组相比，VEGF-C mRNA阳性组的肿瘤淋巴管密度大、腋淋巴结转移率高（均P〈0．05）；所有病例都有不同程度的淋巴管生成，但以肿瘤间质组织中淋巴管生成为主，癌巢中未见到明显的成形淋巴管。肿瘤淋巴管密度与乳腺癌临床分期和腋淋巴结转移呈正相关，临床分期越晚，肿瘤淋巴管密度越高（P〈0．05）；腋淋巴结转移组的肿瘤淋巴管密度比无淋巴结转移组高（P〈0．05）。结论：原发性乳腺癌组织VEGF-C mRNA的表达与乳腺癌肿瘤淋巴管生成、腋淋巴结转移呈正相关；VEGF-C介导的乳腺癌肿瘤淋巴管生成主要发生在肿瘤间质组织中。     

VEGF-C/Flt-4和Podoplanin 在人直肠癌淋巴管生成中的表达

目的探讨血管内皮生长因子C及其受体VEGF—R3（fms—like tyrosine kinase-4,Fit-4）在人直肠腺癌淋巴管生成中的作用。方法用免疫组化SABC染色法观察32例人直肠腺癌组织中VEGF—C及其受体VEGF—R3（fms—like tyrosine kinase-4,Fh-4）和Podoplanin表达的情况。结果直肠腺癌组织周边部淋巴管密度比内部明显增高（P〈0．01）;直肠腺癌组织周边部VEGF—C及其受体VEGF—R3阳性细胞数比内部明显增多（P〈0．01）。VEGF—C及其受体VEGF—R3表达阳性细胞密度和淋巴管密度呈正相关;直肠腺癌组织中VEGF—C及其受体VEGF—R3异位表达在淋巴管内皮细胞上,而在血管中未见表达,差异有显著性（P〈0．01）。结论VEGF—C及其受体VEGF—R3促进直肠腺癌淋巴管的病理生成,淋巴管生成提示在为肿瘤细胞提供养分的同时,也为肿瘤转移创造了条件。     

心脏淋巴管新生及其与心血管疾病预后的关系

 心脏淋巴管的生理病理作用一直未引起人们的重视。但近年来,随着血管内皮生长因子受体-3(vascular endothelial growth factor receptor 3,VEGFR-3)、淋巴管内皮细胞透明质酸受体(lymphatic vessel endothelial hyaluronan receptor 1,LYVE-1)、果蝇同源基因转录因子(prospero homeobox protein 1,Prox-1)、肾小球足细胞膜黏蛋白(podoplanin)等淋巴管内皮细胞标志物的发现,心脏淋巴管的研究迅速发展。心脏淋巴管引流淋巴液,其功能异常可引起心肌水肿、动脉硬化、心律失常、间质纤维化等。深入认识心脏淋巴管的生理病理作用,对于治疗心肌梗死、改善心血管功能、预防心脏手术后并发症等有着重要意义。本文综述了心脏淋巴管的发生、分布以及与心血管疾病预后的关系。     

血管内皮生长因子C及其受体血管内皮生长因子受体3在食管癌淋巴转移中的作用

血管内皮生长因子C(VEGF-C)属于血管内皮生长因子(VEGF)家族成员,是迄今为止发现的第一个淋巴管生成因子,通过与其受体血管内皮生长因子受体3(VEGFR-3)结合后,主要参与肿瘤的淋巴管生成和区域淋巴结转移。VEGFR-3是VEGF-C在淋巴管内皮细胞上较特异的受体,对淋巴管生成发挥重要作用。胚胎时期表达于小静脉及淋巴管,成年后,仅限制表达于淋巴管内皮细胞,可作为成人淋巴管内皮细胞的标志物。本文将对VEGF-C、VEGFR-3的结构、功能及在食管癌淋巴转移中的作用及研究现状予以综述。     

血管内皮生长因子C及其受体3在胃癌组织中的表达及意义

日的探讨血管内皮生长因子C（VEGF-C）和受体（VEGFR-3）在人胃癌组织中的表达及其与微血管，微淋巴管形成，淋巴转移，预后之间的关系。方法应用免疫组织化学染色S-P法对125例胃癌及相应癌旁组织行VEGF-C，VEGFR-3，CD31检测，进行淋巴管密度计数，微血管密度（MVD）计数，并结合临床和病理资料进行分析。结果胃癌中VEGF-C，VEGFR-3的表达与胃癌分化程度呈负相关（均P〈0．01）。VEGF-C，VEGFR-3的表达水平与淋巴转移呈正相关（均P〈0．05）。VEGF-C与VEGFR-3在胃癌中的表达呈正相关（P〈0．01）。淋巴管密度与淋巴结转移（P=0．009），远处转移（P=0．006），临床分期（P〈0．1301），VEGF-C表达（P〈0．1301），VEGFR-3表达（P〈0．001）呈正相关。淋巴管密度与MYD呈正相关（P〈0．01）。VEGF-C，VEGFR-3阳性表达与生存时间，2年生存率呈负相关（P〈0．001）。结论VEGF-C促使胃癌内淋巴管形成，促进胃癌淋巴结转移；VEGF-C，VEGFR-3表达增高，淋巴管密度增加是促使胃癌发生淋巴结转移的重要原因；VEGF-C促进微血管的形成，VEGF—C的表达有推测预后的作用。     

VEGF-C及其受体VEGFR-3在胃癌淋巴转移中的作用

目的:研究胃癌组织中血管内皮生长因子C(VEGF-C)及其受体3(VEGFR-3)的表达与淋巴管生成和淋巴结转移的关系,探讨其在胃癌淋巴转移中的作用和意义.方法:采用RT-PCR检测67例胃癌及正常胃组织中VEGF-C及VEGFR-3 mRNA表达,酶组织化学方法行淋巴管染色并计数,同时分析胃癌淋巴结转移情况.结果:胃癌组织中VEGF-C及VEGFR-3 mRNA阳性表达分别为62.69%(42/67)、58.21%(39/67),显著高于在正常胃组织中的表达[23/67(34.3%)、21/67(31.3%),P＜0.01],胃癌组织中两者表达有密切联系(P＜0.01);在两者阳性表达的病例中,癌组织淋巴管计数和淋巴结转移显著增多(P＜0.05或0.01).结论:VEGF-C作用于VEGFR-3可诱导胃癌组织淋巴管生成,促进淋巴道转移;阻断两者信号转导、抑制胃癌淋巴管生成有望成为抗胃癌淋巴道转移治疗的新靶点.     

肿瘤淋巴管生成及其与宫颈癌关系的研究进展

血管内皮生长因子-C(VEGF-C)和血管内皮生长因子D(VEGF-D)可以诱导肿瘤新生淋巴管形成,并促进肿瘤淋巴道转移。抗肿瘤淋巴管生成成为肿瘤治疗的新策略。宫颈癌早期即可发生盆腔淋巴结转移,其肿瘤淋巴管生成的研究受到重视。研究表明,VEGF-C和D与宫颈癌的淋巴管生成和盆腔淋巴结转移相关,VEGF-C为宫颈癌的不利预后因素。     

Molecular regulation mechanisms of lymphangiogenesis

1Introduction Thelymphaticvascularsystemisahierarchicalnet workofvessels,whichinitiateasblind endedlymphatic capillariesthattakeupexcessfluidandmacromolecules fromtissues.Lymphaticvesselsarealsoessentialforthe uptakeofdietaryfat.Moreover,thelymphaticvascula tureplaysanimportantroleinimmunosurveillanceasa pathwayfortraffickingoflymphocytesandantigen pre sentingcells,whichenterlymphaticcapillariesinthepe ripheryandmigratetothelymphnodestoelicitacquired immuneresponsesinthebody.Thespecialstructur…     

VEGF-C和LYVE-1在卵巢上皮性肿瘤中的表达及其临床意义

目的    探讨血管内皮生长因子-C （VEGF-C）和淋巴管内皮透明质酸受体-1（LYVE-1）在卵巢上皮性肿瘤中的表达及其与临床病理因素之间的关系。方法    免疫组织化学SP法检测61例卵巢肿瘤患者手术标本中VEGF-C及LYVE-1的表达,分析其与临床病理因素的关系。结果   ①VEGF-C及LYVE-1在卵巢上皮性癌中的表达均明显高于卵巢交界性肿瘤和卵巢良性肿瘤（P＜0.01）;②VEGF-C及LYVE-1的表达与卵巢上皮性癌患者年龄、组织学分级、组织学类型无关（P＞0.05）,但与临床分期、淋巴结转移相关（P＜0.05）。结论    VEGF-C和LYVE-1在卵巢上皮性肿瘤淋巴转移过程中发挥了重要作用。     

Progress on antilymphangiogenesis of colorectal cancer

1 IntroductionThe major cause of cancer mortality is themetastatic spread of tumor cells that can occur viamultiple routes ,including the lymphatic vasculature .Recent research has indicated that growth of lym-phatic vessels (lymphangiogenesis) in the vicinity ofsolid tumors correlates with lymphatic metastasis ,and has identified protein growth factors and recep-tors ,principally vascular endothelial growth factor C(VEGF -C) , VEGF -D,and VEGF receptor -3( VEGFR -3) , as drivers of ly…     

急性炎症淋巴管变化与血管内皮生长因子-C表达关系的实验研究

目的 :观察急性炎症组织不同时期血管内皮生长因子 (VEGF- C)的表达及淋巴管变化。方法 :通过急性炎症动物模型炎症组织 VEGF- C免疫组化染色、淋巴管酶组化染色、光镜及图像分析观察淋巴管体视学参数 :包括总体面数密度 (TNa)、有腔淋巴管面数密度 (ONa)。结果 :不同时期 (周 )急性炎症与正常对照相比 ,VEGF- C、TNa无统计学差异 (P >0 .0 5 ) ,Ona有明显增加 (P <0 .0 5 ) ,不同时期之间差异无统计学意义 (P >0 .0 5 )。结论 :急性炎症不仅没有明显的淋巴管增生 ,而且也没有明显的 VEGF- C表达增高 ,管腔增大仅是适应功能的改变。     

Lymphoscintigraphic evaluation of chronic lower limb oedema

Ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), venography, lymphoscinti-graphy (LS) and contrast lymphography are frequently utilized in the evaluation of lower limb oedema but no clinical data from the Caribbean have been published on the role of LS despite its well-recognized clinical application. The successful clinical application of CT, colour doppler sonography and MRI in differentiating the various causes of lower limb oedema is well understood. Lymphoscintigraphy has found less acceptability especially in the Caribbean where nuclear imaging techniques are only now currently being developed. This paper describes the initial experience with this technique in 15 patients over a five-year period and discusses its value when lower limb lymphoedema is suspected. Scintigrams were analyzed for visualization of lymph vessels and lymph nodes, dilatation of lymphatic vessels, collaterals and dermal back flow. Lymphoscintigrams were classified as normal (n = 5) or consistent with lymphoedema (n = 10). Failure to visualize lymphatic vessels occurred in two cases of suspected primary lymphoedema. In the remaining eight cases of secondary lymphoedema, a positive study based on altered lymphatic flow and anatomy was recorded. An alternative explanation was offered in three out of five cases in which a normal lymphoscintigram was obtained.     

Inhibition of lymphangiogenesis,nodal and lung metastasis by dihydroartemisinin in mice bearing Lewis lung carcinoma

Objective：To investigate the activity of anti-malarial dihydroartemisinin （DHA） on tumor growth, lymphangiogenesis, nodal and lung metastasis and survival in mice bearing Lewis lung carcimoma （LLC）. Methods： The models of C57BL/6 mice transplantation tumors were established via subcutaneous injection of LLC cells and divided into 4 groups： control group, DHA group, DHA＋ferrous sulfate （FS） group and FS group, with 25 mice in each group. Tumor volumes and weights, nodal and lung metastasis, and survival were monitored. Tumor lymphatic microvessel density （LMVD） was determined by lymphatic vessel endothelial hyaluronan receptor-1 （LYVE-1） immnohistochemistry. After LLC cells were treated with DHA or DHA＋FS, protein and mRNA levels of vascular endothelial growth factor （VEGF） -C were evaluated by Western blotting and real time quantitative RT-PCR, respectively. Results： Oral administration of DHA or DHA＋FS inhibited lymph node and lung metastasis, and prolonged survival. However, no significant tumor growth retardation effect was observed when mice were treated with DHA alone. The inhibited tumor metastasis was related to the decreased LMVD in the peritumoral regions, but not in the intratumoral regions. DHA significantly down-regulated the expression of VEGF-C protein and mRNA in LLC cells. Conclusion： DHA effectively inhibits LLC transplantation tumor lymphangiogenesis, nodal and lung metastasis, and may be a promising chemotherapeutic agent for controlling lung cancer metastasis by decreasing VEGF-C expression.     

非小细胞肺癌中VEGF-C?PDGF-BB与淋巴管生成和淋巴结转移的关系

目的:探讨血管内皮生长因子C(VEGF-C)和血小板衍生生长因子BB(PDGF-BB)在非小细胞肺癌(NSCLC)中的表达与淋巴管生成和淋巴结转移的关系.方法:分别应用免疫组化SP法和Envision System法检测40例NSCLC和10例肺良性病变组织中VEGF-C和PDGF-BB的表达;应用淋巴管特异标志 Podoplanin 检测NSCLC中淋巴管密度(LVD),并做相关统计分析.结果:VEGF-C和PDGF-BB在NSCLC中阳性表达率均显著高于肺良性病变(VEGF-C:62.5% vs 10%,P<0.05;PDGF-BB:60% vs 10%,P<0.05).淋巴结阳性组的VEGF-C阳性表达率显著高于淋巴结阴性组 (94.1%vs 39.1%,P<0.05),但未发现PDGF-BB表达与淋巴结有关(76.5%vs 47.8%,P>0.05).NSCLC中淋巴结阳性组的LVD显著高于淋巴结阴性组(16.58±2.38vs 9.88±1.93,P<0.05),VEGF-C 和 PDGF-BB阳性表达组的LVD均显著高于阴性表达组(VEGF-C:14.74±3.62 vs 9.37±1.35,P<0.05;PDGF-BB:13.84±4.23 vs 11.06±2.90,P<0.05).NSCLC中 VEGF-C与PDGF-BB的表达具有显著相关性(rs=0.422,P<0.05).结论:淋巴管生成是淋巴结转移的一个重要因素;PDGF-BB参与了淋巴管生成,但对于促进淋巴结转移可能不是必要的:VEGF-C通过参与淋巴管生成而促进淋巴结转移,其预测NSCLC发生淋巴结转移可能性的价值优于PDGF-BB;PDGF-BB和VEGF-C在促进淋巴管生成的作用上可能具有相关性.     

Quantitative analysis of lymphangiogenic markers in human gastroenteric tumor

BACKGROUND: Lymphatic spread of gastroenteric tumor cells to regional lymph nodes is one of the early events in metastatic cancers and is often associated with distant metastatic spread and poor prognosis. Expression levels of newly described lymphatic endothelial markers, LYVE-1, VEGF-C, VEGF-D and the VEGF receptors VEGFR-3 were assessed in our study. METHODS: Paired (tumor and corresponding normal tissue) samples were obtained. The expression level of each factor was determined using RT-PCR and quantified by using a real-time quantitative PCR (RT-QPCR) technique, with respective cloned cDNA plasmids as internal standards. RESULTS: The expression of VEGF-C and lymphatic endothelial marker VEGFR-3 was significantly greater in patients with lymph node metastasis than in those without metastasis, but no different expression level of VEGF-D and LYVE-1 was detected in both groups of patients. Lymphatic vessel density (LVD), which was assessed by immunohistochemistry for LYVE-1, was correlated with lymphangiogenesis factors and lymph node metastasis. Expression of VEGF-C and VEGFR-3 was significantly associated with higher peritumoral LVD than normal group, and LVD was found greater in the node-positive group than in the node-negative group. CONCLUSIONS: These results indicate that quantitative analysis of lymphangiogenic marker VEGF-C and VEGFR-3 in gastroenteric specimens may be useful in predicting metastasis of gastroenteric cancer to regional lymph nodes, but the role of LYVE-1 in predicting metastasis of gastroenteric cancer requires further analysis.