Effect of vascular endothelial growth factors A,C, and D in HIV-associated pre-eclampsia

Objective: To measure and correlate the level of vascular endothelial growth factors A, C, and D in HIV-associated pre-eclampsia.

Methods: VEGF-A, VEGF-C, and VEGF-D were measured in serum of 76 normotensive and pre-eclamptic pregnant women stratified by HIV status using Bio-Plex.

Results: No significant difference was shown between pre-eclamptic and normotensive and between HIV negative and positive women. A strong significant positive correlation was demonstrated between VEGF-A and VEGF-C, VEGF-A and VEGF-D, and VEGF-C and VEGF D (p < 0.0001).

Conclusion: This study demonstrates a significant correlation between VEGF-A, VEGF-C, and VEGF-D and no difference in pre-eclamptic and normotensive pregnant women stratified by HIV status suggesting some neutralization of the immune response in HIV-associated pre-eclampsia.     

ＨＭＧＢ１表达载体转染结肠癌细胞对ＶＥＧＦ-Ｄ表达的影响

目的：构建ＨＭＧＢ１表达载体,转染结肠癌细胞,研究其对结肠癌细胞中血管内皮生长因子Ｄ（ＶＥＧＦ-Ｄ）表达的影响。方法：将分离得到的淋巴细胞总ＲＮＡ反转录合成ｃＤＮＡ,以此为模板进行ＰＣＲ扩增得到ＨＭＧＢ１基因;随后酶切转入载体ｐＭＤ１８Ｔ,通过亚克隆转入载体ｐＬｘｓｎ,得到重组质粒。重组体质粒经酶切鉴定后,并对插入的ＨＭＧＢ１基因片段进行测序,将已鉴定的阳性重组质粒用脂质体介导转染ＨＣＴ１１６细胞。通过ＲＴ-ＰＣＲ和Ｗｅｓｔｅｒｎｂｌｏｔｔｉｎｇ检测ＨＭＧＢ１和ＶＥＧＦ-Ｄ的表达情况。结果：成功构建含ＨＭＧＢ１的表达载体。ＲＴ-ＰＣＲ和Ｗｅｓｔｅｒｎｂｌｏｔｔｉｎｇ检测发现转染表达ＨＭＧＢ１载体的ＨＣＴ１１６细胞中ＨＭＧＢ１和ＶＥＧＦ-Ｄ的表达均增高。结论：ＨＭＧＢ１可以通过促进结肠癌细胞中ＶＥＧＦ-Ｄ的表达,诱导淋巴管生成,从而促进其淋巴结转移。     

细胞因子IL-2和IL-6对胰腺癌细胞表达VEGF-D的调节

目的探讨细胞因子白细胞介素2（IL-2）和白细胞介素6（IL-6）对胰腺癌细胞表达VEGF-D的调节。方法以细胞因子IL-2或IL-6分别刺激胰腺癌细胞株SW1990和BXPC-3后用逆转录 聚合酶链式反应技术（RT-PCR）分析其VEGF-D基因的表达。结果IL-2使细胞株SW1990和BXPC-3产生VEGF-D mRNA减少;IL 6使细胞株SW1990产生VEGF-D mRNA增加,但对细胞株BXPC-3产生VEGF-D mRNA无明显影响。结论IL-2抑制胰腺癌细胞VEGF-D mRNA的表达,从而抑制胰腺癌淋巴结转移;IL-6促进某些胰腺癌细胞VEGF-D mRNA的表达,但对胰腺癌细胞生物学特性的影响有待于进一步深入研究。     

血清血管内皮生长因子-D (VEGF-D)在多发囊泡性肺疾病(PLD)鉴别诊断中的价值

 目的    探讨血清血管内皮生长因子-D(vascular endothelial growth factor-D,VEGF-D)在淋巴管平滑肌瘤病(lymphangioleiomyomatosis,LAM)中的表达及其在多发囊泡性肺疾病(polycystic lung disease,PLD)鉴别诊断中的价值。方法    采用酶联免疫吸附试验检测50例LAM患者、34例其他多发囊泡性肺疾病(other polycystic lung disease,OPLD)和20例健康对照者的血清VEGF-D水平。结果    50例LAM均为确诊患者,其中33例通过病理确诊,23例为肺活检,5例为腹膜后肿物活检,5例为肾血管平滑肌脂肪瘤(renal angiomyolipoma,AML)活检。50例LAM患者中21例伴有乳糜胸,2例伴有乳糜腹,17例伴有AML,3例伴有结节性硬化症。50例LAM患者首发症状的年龄为19～60岁,34例OPLD患者首发症状的年龄为30～69岁,20例健康对照者的年龄为24～49岁。LAM组和健康对照组的血清VEGF-D水平分别为(3 986.1±361.2) pg/mL和(413.4±33.2) pg/mL,差异有统计学意义(P<0.001)。ROC曲线的AUC为0.995,最佳临界值为692.5 pg/mL,其敏感性和特异性分别为98%和100%。OPLD组的血清VEGF-D水平为(505.7±25.6) pg/mL,与LAM组相比差异有统计学意义(P<0.001)。ROC曲线的AUC为0.991,最佳临界值为901.0 pg/mL,其敏感性和特异性分别为94%和100%。结论    LAM患者血清VEGF-D水平显著升高,具有较高的敏感性和特异性,在LAM和OPLD鉴别诊断中有重要价值。     

Chronic VEGFR-3 signaling preserves dendritic arborization and sensitization under stress

Dendritic arborization is critical for the establishment and maintenance of precise neural circuits. Vascular endothelial growth factor D (VEGF-D), well-characterized as a “lymphangiogenic” growth factor, reportedly maintains dendritic arborization and synaptic strength in the hippocampus of adult mice through VEGF receptor (VEGFR-3) signaling. Here, we investigated the effect of chronic VEGFR-3-specific activation on adipose arbor morphometry using the Adipo-VD mouse, a model of inducible, adipose-specific VEGF-D overexpression. We examined whether adipose tissue innervation was preserved or functionally different in Adipo-VD mice during stress in vivo and if VEGFR-3 signaling afforded neuroprotection to challenged neurons in vitro. Chronic VEGFR-3 signaling in Adipo-VD subcutaneous adipose tissue resulted in a reduction in the dendrite length, dendritic terminal branches (filament length), and dendritic terminal branch volume (filament volume), but increased dendrite branching. We also identified reduced stimulus-evoked excitatory sympathetic nerve activity in Adipo-VD mice. Following 6-hydroxydopamine (6-OHDA) denervation, Adipo-VD dendritic arbors were preserved, including improved dendritic branch volume, length, and dendritic branches than in wildtype tissues. In vitro, we found that chronic elevation of VEGFR-3 signaling in developing mVC neurons changes the dendritic arbor complexity and improves stress-induced structure remodeling. Developing neurons are conferred neuroprotection against stress, potentially by upregulation of proteolytic conversion of pro-BDNF to mature BDNF. Mature neurons, however, display improved dendritic arbor complexity, and unaltered dendritic structural remodeling and improved resistance to stress with VEGFR-3 signaling. Overall, chronically increasing VEGFR-3 signaling in neurons has a synergistic impact on neurosensitization and neuroprotection during stress.     

circEHBP1 promotes lymphangiogenesis and lymphatic metastasis of bladder cancer via miR-130a-3p/TGFβR1/VEGF-D signaling

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The relevance of cell type- and tumor zone-specific VEGFR-2 activation in locally advanced colon cancer

Background

For the successful therapeutic use of inhibitors of the vascular endothelial growth factor receptor (VEGFR) pathway detailed knowledge of the mechanisms leading to tumor progression is indispensable. The main goal of this study was to determine the relevance of the VEGFR-2 activating pathway for colon carcinoma (CC) metastasis. The initial event is ligand-induced receptor activation through tyrosine autophosphorylation.

Methods

VEGFR-2, its ligands VEGF-C and VEGF-D and the phosphorylated (activated) receptor forms pVEGFR-2^Tyr1175 and pVEGFR-2^Tyr1214 were investigated immunohistochemically in different tumor compartments (intratumoral (zone 1) - invasive front (zone 2) – extratumoral soft tissue (zone 3)) and various cell types (tumor cells, inflammatory cells, macro- and microvasculature) in 84 non-metastatic, lymphogenous-metastatic and haematogenous-metastatic CC.

Results

VEGF-D produced by tumor cells has an autocrine affinity for its receptor VEGFR-2. In tumor budding regions VEGF-D-induced receptor activation by autophosphorylation at Tyr1214 seems to be a possible initial event of the VEGFR-2-mediated signaling pathway, but without effect on metastatic behaviour. In inflammatory cells of almost all CC VEGFR-2 phosphorylation at Tyr 1175 and Tyr 1214 was detectable without accompanying receptor expression, suggesting receptor activation without cell surface expression. Peritumoral inflammatory cells also expressed paracrine acting VEGF-C. The autocrine VEGF-D/VEGFR-2 signaling axis and receptor autophosphorylation at Tyr1214 appear to be main events for capillaries in all three tumor zones and for small vessels in zone 1 and 2. Independent of the metastatic status a large number of cases with capillary immunopositivity in the angiogenically active invasive front was documented, especially for VEGF-D, VEGFR-2 and pVEGFR-2^Tyr1214. VEGFR-2 positive extratumoral capillaries were significantly more common in distant metastatic CC. In all tumor compartments the investigated biomolecules were also detected in different frequencies in the macrovasculature, which is responsible for sufficient tumor vascularization. In addition, vascular paracrine-acting VEGF-C production was widely detected, but without zone and vessel-type dependence.

Conclusions

The VEGFR-2 activating pathway is closely involved in tumor cell-associated, vessel-mediated and immuno-inflammatory processes in colon carcinoma and appears to contribute to tumor survival and growth as well as maintenance of the infiltrative phenotype rather than to promote metastasis.     

血管内皮生长因子VEGF-C和VEGF-D在卵巢上皮癌的表达及其预后研究

目的：观察血管内皮生长因子（VEGF）-C 和 VEGF-D 在卵巢上皮癌组织内的表达情况及其与临床病理特征的关系,为临床抗淋巴管生成治疗肿瘤及评价患者预后提供理论依据。方法收集2011－2013年新疆医科大学第一附属医院和阿克苏地区第一人民医院2004－2014年1月确诊为卵巢癌患者78例的手术切除组织标本,其中淋巴结转移组41例,无淋巴结转移组37例。应用免疫组化技术观察 VEGF-C 和 VEGF-D 在卵巢癌组织内的表达。以 D2-40作为淋巴管内皮特异性标记物。结果无淋巴结转移组的 VEGF-C 和 VEGF-D 表达率和表达强度明显低于淋巴结转移组（P ＜0．01）。D2-40在无淋巴结转移组癌组织内淋巴管数密度明显低于淋巴结转移组（P ＜0．05）。结论VEGF-C 和 VEGF-D 高表达可以促进卵巢上皮癌组织淋巴管生成,进而促进卵巢上皮癌发生淋巴道的侵袭和转移。     

联合检测MMP-7 VEGF-D和KAI1在胰腺癌预后判断中的价值

目的：探讨将基质金属蛋白酶-7（MMP-7）、血管内皮生长因子-D（VEGF-D）和KAI1进行联合检测（简称MVK1在胰腺癌预后判断中的价值。方法：应用免疫组化法检测胰腺癌中MMP-7、VEGF—D和KAI1的表达，分析MVK的联合表达模式对预后的影响。结果：MVK的联合表达模式中无不利预后因素组，其胰腺癌术后中位生存时间为12个月；单个不利预后因素组，其术后中位生存时间为8个月；两个不利预后因素组，其术后中位生存时间为6个月；3个不利预后因素组．其术后中位生存时间为5个月。各组间均具有显著性差异（P=0．0045，P=0．0003，P=0．0015）多因素分析结果表明，MVK为胰腺癌独立预后指标。结论：MVK的联合表达模式对更准确反映胰腺癌的预后有价值．值得进一步研究。