抑制血管生成对颊粘膜鳞癌微血管构筑的影响

目的 了解抑制血管生成对颊癌微血系统空间配布的影响,进而了解对肿瘤局部生长、浸润及转移的作用。方法 应用鱼精蛋白进行实验治疗,结合扫描电镜肿瘤生血管系统的变化规律。结果 鱼精蛋白确有抑制智力;这生成的作用,主要表现为延缓肿瘤血管生成的发和因管空间结构的建立,促进血管成熟,因此而抑制肿瘤生长、浸润和转移。结论 通过抑制血和生成有可效地阻止肿瘤生长和转移所依赖的血和系统建立和发展,从而限制肿瘤细胞局部     

Inhibition of inflammatory angiogenesis in rats by loco-regional administration of hydrocortisone and protamine

We have studied the antiangiogenetic effects of hydrocortisone and protamine given intra-arterially. The cornea of male, Sprague-Dawley rats were cauterized with silver nitrate. The following treatments were given :30 g hydrocortisone topical (t.p.), b.i.d., 50 mg/kg/day intraperitoneally (i.p.) or intra-arterially (i.a.), 10 mg/ kg/day protamine i.p. or i.a. Saline was administered to the control groups. In separate experiments we also evaluated the anti-inflammatory effects of hydrocortisone, i.p., on the cauterized corneas.Five days after cauterization, the animals were killed, exsanguinated and India ink was injected to show the network of neovessels. The percentage area of the cornea covered by neovessels was measured morphometrically and evaluated statistically. Hydrocortisone t.p. (–84%), i.a. (–60%) and protamine i.a. (–44%) significantly inhibited angiogenesis in the cauterized cornea. Either drugs, i.p., had any antiangiogenetic effects, but hydrocortisone significantly reduced cell infiltration of the corneas. The results suggest that locoregional administration of antiangiogenetic drugs might be clinically useful.     

卵巢异位囊肿囊内液中VEGF、IL-8的测定及其意义

目的了解卵巢子宫内膜异位症患者异位囊肿囊内液中血管内皮生长因子(VEGF)、白细胞介素8(IL-8)的水平。方法收集13例卵巢异位囊肿的囊内液为内异症组,以12例卵巢单纯囊肿为对照,应用酶联免疫吸附分析法(ELISA)分别测定VEGF、IL-8水平。结果①内异症组分别为82.6±17.6ng/L和207.3±33.3ng/L,高于对照组的19.4±10.0ng/L和80.2±11.3ng/L,有显著性差异(P<0.01);②IL-8水平与异位囊肿直径呈负相关,VEGF水平与囊肿直径无相关性(r=-0.401,P>0.05);③VEGF、IL-8水平与RAS评分无相关性,P>0.05。结论VEGF和IL-8两种血管生成因子可能是卵巢子宫内膜异位症发病机制中的一个重要因素。     

乳腺癌肿瘤血管生成的临床病理学意义

肿瘤血管生成（ＴｕｍｏｒＡｎｇｉｏｇｅｎｅｓｉｓ，ＴＡ）是目前肿瘤研究的重要课题，其研究目的在于探讨ＴＡ的预后价值以及预测肿瘤对抗血管生成药物的反应。本文应用第八因子相关抗原多克隆抗体对６５例乳腺浸润性导管癌（以下简称乳腺癌）进行了微血管的定量研究。结果显示：腋下淋巴结阳性病例组织的微血管密度（ＭｉｃｒｏｖｅｓｓｅｌＤｅｎｓｉｔｙ，ＭＶＤ）（１２９．７±４４．９）明显高于腋下淋巴结阴性（ＮｏｄｅＮｅｇａｔｉｖｅＢｒｅａｓｔＣａｎｃｅｒ，ＮＮＢＣ）病例组的ＭＶＤ（７９．６±３３．６），差异呈极显著性（Ｐ＜０．００１）；发生术后复发及远处转移的病例的ＭＶＤ均值高达１４５．３；以上结果提示乳腺癌ＭＶＤ与肿瘤转移、复发均密切相关。我们认为乳腺癌ＭＶＤ可反映其血供状态，ＭＶＤ高的病例微血管丰富，肿瘤组织生长快，癌细胞易于进入微循环而发生转移     

促红细胞生成素在子宫内膜异位症组织的表达

目的探讨促红细胞生成素(Epo)在子宫内膜异位症(EMs)发生中的病理生理作用及其临床意义。方法应用免疫组织化学SABC法、mRNA原位杂交法检测39例子宫内膜异位症的异位内膜及35例正常子宫内膜Epo的组织定位和表达强度,并对比其差异。结果Epo、EpomRNA的表达主要定位于腺体细胞胞质、胞核,间质细胞表达不明显。异位内膜组织Epo、EpomRNA表达分别为9.68±2.90,3.08±0.48,明显高于正常对照的4.54±2.86,0.55±0.46,差异有高度显著性(P<0.01);Epo、EpoRNA在EMs组、正常对照组的增殖期和分泌期表达相比,差异均无显著性(P>0.05);EMs组EpomRNA与AFS分期呈正相关(r=0.979,P=0.013)。结论Epo通过旁分泌或自分泌方式过度转录表达引起的局部新生血管生成增强可能是子宫内膜异位症发生的机制之一。     

Cytochrome P450 epoxygenases as EDHF synthase(s)

The metabolism of arachidonic acid by cytochrome P450 (CYP) epoxygenases generates epoxyeicosatrienoic acids (EETs) which affect numerous cellular process including Ca(2+) signaling and the activity of Ca(2+)-dependent K(+) channels. The expression of the CYP epoxygenase(s) that generate EETs in endothelial cells is not constitutive but is determined by a number of physical (fluid shear stress and cyclic stretch) and pharmacological stimuli which also affect responses attributed to an endothelium-derived hyperpolarizing factor (EDHF). This review summarizes the role played by EETs, and the enzymes that generate and metabolize them, in EDHF-mediated responses.     

Early increase of plasma soluble VEGFR-2 is associated with clinical benefit from second-line treatment of paclitaxel and ramucirumab in advanced gastric cancer

Ramucirumab plus paclitaxel is considered the standard of care in the second-line treatment of gastric carcinoma (GC). The aim of this study was to evaluate plasma vascular endothelial growth factor-A (VEGF-A), VEGF-D, and circulating soluble VEGF receptor-2 (sVEGFR-2) as possible markers of resistance or response to ramucirumab administered with paclitaxel in pretreated metastatic GC patients. Plasma samples were collected at different time points (on days 1 and 15 of the first 3 cycles, at best radiologic response and at disease progression). VEGF-A, VEGF-D and sVEGFR-2 were analysed by ELISA. Correlations of biomarker baseline levels or dynamic changes with outcome measures were assessed. Progression-free survival (PFS) was the primary endpoint of the study. Forty-one patients were enrolled. VEGF-A and VEGF-D, but not sVEGFR-2, values significantly increased during treatment compared to baseline (P < 0.001). A positive correlation between VEGF-A and sVEGFR-2 at cycle 2 was found (P=0.045). At univariate analysis, higher baseline levels of VEGF-A were associated with worse OS (P=0.015). Early increase of sVEGFR-2 levels after the first treatment cycle was the only factor associated with longer PFS (6.6 vs. 3.6 months, P=0.049) and OS (18.6 vs. 5.2 months, P=0.008). Significance of sVEGFR-2 early increase was retained at multivariate analysis for OS (HR 0.32; 95% CI 0.12-0.91; P=0.032). The reported results confirmed the prognostic role of baseline VEGF-A and, with the limitations of the limited sample size and the lack of a control arm, suggested that the early increase of sVEGFR-2 after 1 cycle of treatment could be a potential predictive biomarker of benefit from second-line ramucirumab plus paclitaxel in GC.     

水通道蛋白1在喉癌组织中的表达及分布

目的：明确水通道蛋白1（AQP1）在喉癌组织中的表达和分布,并探讨其在喉癌发病中可能的作用机制及意义。方法：取喉癌组织20例及癌旁正常组织15例,应用RT-PCR,Western blot,免疫组织化学技术检测AQP1蛋白在喉癌和正常对照组织中的表达及分布。结果：AQP1表达于正常喉黏膜固有层的血管内皮细胞及喉黏膜腺体上。在喉癌组中主要表达于肿瘤的血管内皮细胞,在肿瘤上皮细胞和癌巢中亦有表达。喉癌中AQP1 mRNA及蛋白表达水平较癌旁正常组织增多,二者之间差异有统计学意义。结论：AQP1在喉癌组织中表达增高,在癌旁正常组织中较低,提示AQP1在喉癌发病中的重要作用有待深入研究。     

南蛇藤总萜对Hepal-6荷瘤小鼠VEGF、CECs的影响

目的 观察南蛇藤总萜对Hepal-6荷瘤小鼠外周血VEGF、CECs的影响.方法 采用常规无菌接种技术制作小鼠肝癌Hepal-6移植性肿瘤模型,观察南蛇藤总萜高、中、低剂量(40 mg/kg、20 mg/kg、10 mg/kg)对Hepal-6荷瘤小鼠外周血VEGF、CECs表达的影响.结果 南蛇藤总萜在20 mg/kg时,外周血VEGF (45.24±21.36) pg/ml、CECs (0.83±0.10)％表达明显降低,与阴性对照组(0.9％生理盐水)比较,差异有统计学意义(P＜0.01).结论 南蛇藤总萜可明显降低VEGF、CECs表达,这一作用可能与南蛇藤总萜抑制肝癌血管生成有关.     

Tumor’host interaction in the optimization of paclitaxel-based combination therapies with vascular targeting compounds

Targeting of the tumor stroma, including the tumor vasculature, represents a new frontier in the treatment of malignancy. Preclinical studies and clinical experiences have established that stroma-directed novel agents must be combined with conventional therapies in order to achieve relevant therapeutic efficacy. Here we review our preclinical experience on combinations of paclitaxel with a tyrosine kinase receptor inhibitor of angiogenesis (SU6668) and a vascular disrupting agent (VDA, ZD6126), and discuss the critical factors that determine the outcome of these treatments. We also analyze the relevance of the intrinsic sensitivity of the tumor to the drugs, as well as the possibility that the two combined agents synergistically affect the vasculature or independently target the host and the tumor compartments. Finally, we discuss the need to carefully optimize scheduling and sequencing, through the use of reliable end points, in order to avoid negative pharmacological interactions and to improve the antineoplastic efficacy of paclitaxel-based combination treatments.