胰岛素样生长因子-Ⅰ受体在人皮肤血管瘤不同分期的表达

目的：探讨胰岛素样生长因子-Ⅰ受体与血管瘤发生发展的关系。方法：采用免疫组化SP法和半定量RT-PCR检测不同分期血管瘤中IGF-IR的表达水平，并与血管畸形及正常皮肤进行比较。结果：SP法和半定量RT-PCR结果均显示增殖期血管瘤内皮细胞IGF-IR表达水平增高，与血管畸形及正常皮肤组织间差异显著；而消退期的IGF-IR表达水平降低与血管畸形及正常皮肤相比，差异无显著性。结论：IGF-IR与血管瘤的发生发展有密切关系，为寻找皮肤血管瘤的诊断与治疗的新靶点提供了新的思路。     

PI3K/AKT信号转导通路和VEGF在子宫内膜异位症中的表达

目的:探讨子宫内膜异位症(EMs)患者中磷脂酰肌醇-3激酶/蛋白激酶B(PI3K/AKT)和血管内皮生长因子(VEGF)表达水平。方法:采用EMs患者32例,取在位子宫内膜和异位内膜,无EMs患者34例,取子宫内膜,作为对照组。采用半定量RT-PCR法检测PI3K/AKT与VEGFmRNA表达,ELISA法检测PI3K/AKT蛋白和VEGF蛋白表达。结果:正常子宫内膜、异位子宫内膜和在位子宫内膜PI3K、AKT和VEGF mRNA和蛋白表达水平差异有统计学意义(P0.01)。异位内膜PI3K、AKT和VEGF的mRNA和蛋白的表达均高于在位内膜及正常内膜(P0.01)。EMs中,Ⅰ、Ⅱ期PI3K、AKT和VEGF mRNA和蛋白的表达与Ⅲ、Ⅳ期异位内膜相比,均无显著性差异(P0.05)。结论:PI3K/AKT信号转导通路和VEGF共同参与EMs的发生和发展。     

血管生成素-2及其受体在子宫内膜异位症发生发展中的作用

目的:探究血管生成素-2及其受体在子宫内膜异位症中的表达。方法:搜集孝感市中心医院与广东省妇幼保健院2014年4月至2015年4月诊治的82例患有子宫内膜异位症病患作为研究组,包括研究A组在位内膜和研究B组异位内膜,再选取20例正常子宫内膜的女性作为参照组,分析血管生成素为-2及其受体的表达。结果:(1)研究A组和B组的增生期和分泌期血管生成素-2的平均光密度显著高于参照组;研究A、B组分泌期的血管生成素-2的平均光密度显著高于增生期,而参照组增生期高于分泌期,P0.05;(2)研究A组和B组的增生期和分泌期受体Tie-2的平均光密度显著高于参照组;研究A、B组增生期的受体Tie-2的平均光密度显著高于分泌期,P0.05;(3)研究A、B组血管生成素-2的阳性表达率81.0%、66.7%显著高于参照组30.0%;研究A组的血管生成素-2的阳性表达率80.5%显著高于研究B组65.9%,P0.05。(4)研究A、B组受体Tie-2的阳性表达率53.6%、61.0%显著高于参照组25.0%;研究B组受体Tie-2的阳性表达率61.0%显著高于研究A组53.6%,P0.05。结论:通过检测血管生成素-2及其受体Tie-2在子宫内膜异位症中的表达,可以有效诊断病情的发生和发展情况,为临床治疗提供依据。     

胰岛素样生长因子-Ⅰ受体蛋白在瘕痕疙瘩中的表达

研究发现胰岛素样生长因子（IGF）-Ⅰ能降低烧伤后增生性瘢痕中成纤维细胞合成胶原酶mRNA的水平和胶原酶的活性。IGF-Ⅰ的功能主要靠与IGF-Ⅰ受体（IGF-Ⅰ R）结合来介导完成，成熟的IGF-Ⅰ 由4个亚基（α2β2)组成，位于细胞外的α链具有配体结合部位，通过二硫链与β链共价连接。β链与跨膜和胞内部分，具有酪氨酸激酶活性部位。     

检测子宫内膜异位症中PI3K/Akt通路和VEGF的临床意义

目的:探讨子宫内膜异位症患者中血管内皮生长因子(VEGF)、磷脂酰肌醇-3激酶/蛋白激酶B(PI3K/Akt)表达水平及其与血管生成的关系,并且探讨VEGF与PI3K在调控血管生成过程中的相互关系。方法:利用S-P方法对32例EM手术标本和30例子宫肌瘤中VEGF、Akt及微血管密度(MVD)的表达进行检测。结果:EM中正常内膜、在位内膜和异位内膜Akt、VEGF阳性表达率分别为20.0%(6/30)、37.5%(12/32)、84.4%(27/32)、60.0%(18/30)、75.0%(24/32)、87.5%(28/32);EM中正常内膜、在位内膜和异位内膜MVD分别是(10.37±5.24)、(19.14±7.10)、(48.24±10.54)。Akt、VEGF和血管密度在EM中异位内膜较正常内膜组高表达,在调控血管生成过程中,Akt与VEGF呈正相关。结论:PI3K/Akt、VEGF均参与EM的发生发展,在EM血管生成中发挥关键作用,共同参与EM过程。     

阿维A对HaCaT细胞体外凋亡和胰岛素样生长因子结合蛋白7及血管内皮生长因子表达的影响

目的 探讨阿维A对HaCaT细胞体外凋亡和胰岛素样生长因子结合蛋白7（IGFBP7）及血管内皮生长因子（VEGF）表达的影响。 方法 将10-5、10-6、10-7、10-8 mol/L的阿维A分别作用于HaCaT细胞24、48、72 h后,采用CCK8法检测细胞增殖情况;流式细胞仪检测阿维A对HaCaT细胞凋亡率的影响;Western印迹和RT-PCR法检测阿维A对HaCaT细胞IGFBP7、VEGF蛋白及其mRNA表达的影响。 结果 10-8 mol/L阿维A处理HaCaT细胞48 h时表现出对细胞增殖的抑制作用,随着时间延长和药物浓度升高,抗增殖作用亦增强,当药物浓度增加到10-5 mol/L时,48 h和72 h的抑制率分别为39.94% ± 2.27%和49.77% ± 1.87%。与对照组相比,10-5 mol/L阿维A作用48 h后,凋亡率由1.803% ± 0.313%（对照组）上升至7.617% ± 0.767%（阿维A组）（P ＜ 0.05）,IGFBP7的表达由0.436 ± 0.013上升至0.939 ± 0.040（P ＜ 0.05）,IGFBP7 mRNA的表达由0.190 ± 0.056上升至0.872 ± 0.079（P ＜ 0.05）,VEGF的表达由0.798 ± 0.036下降至0.213 ± 0.032（P ＜ 0.05）,VEGF mRNA的表达由0.933 ± 0.054下降至0.274 ± 0.041（P ＜ 0.05）。 结论 阿维A可促进HaCaT细胞的体外凋亡,并可在蛋白及mRNA水平上调IGFBP7及下调VEGF的表达。     

子宫内膜异位症与不孕

子宫内膜异位症(EM)临床表现多种多样,为不孕症诊治中最常遇到的疾患之一。该症引起不孕的机理尚不十分明了,诊断与治疗存在的问题尚多。本文将近几年对该症的研究进展加以综述,指出目前主要的病因学说有体腔上皮化生说、移植说、免疫说等。EM的治疗目标为去除疼痛症状、去除异位的内膜组织、恢复其妊孕能力。具体疗法有期待疗法、药物治疗、外科疗法以及人工辅助受孕技术(ART))等。     

子宫内膜异位症生育指数预测促性腺激素释放激素激动剂治疗子宫内膜异位症效果的价值探讨

目的:探讨子宫内膜异位症生育指数预测促性腺激素释放激素激动剂治疗子宫内膜异位症的临床效果。方法:选择2011年1月至2013年6月我院收治的子宫内膜异位症合并不孕者232例(观察组112例、对照组120例),所有患者均实施腹腔镜手术治疗,对照组于术后月经来潮前5d采用GnRH-a行肌肉注射,观察组则结合EFI对使用GnRH-a治疗效果进行评估,调整GnRH-a治疗持续时间、剂量及是否联合雌孕激素治疗等,比较两组治疗后6个月时生殖相关激素水平、治疗过程中发生的不良反应、不同EFI评分累积妊娠率及妊娠方式。结果:治疗后,观察组E2和PRL水平均基本处于正常,且显著低于对照组(P0.05),骨密度水平高于对照组(P0.05),观察组发生潮热、生殖道干涩、闭经及骨质疏松的比例显著低于对照组(P0.05),观察组0~4分、5~7分及8~10分各EFI评分累积妊娠率均显著高于对照组(P0.05),观察组自然妊娠比例显著高于对照组(P0.05),使用促排卵治疗后妊娠比例及人工受精妊娠比例均显著低于对照组(P0.05)。结论:在使用GnRHa治疗时,对于EFI评分超过7分者,可在严格监测体内激素水平的同时继续GnRHa治疗;而针对EFI评分低于4分者,建议停止GnRHa治疗,早期人工辅助生殖措施。     

会阴部子宫内膜异位症1例

患者女,29岁.会阴部丘疹、结节伴疼痛8个月余.患者大约8个月前会阴后联合部出现小的丘疹,局部有轻微疼痛感, 未引起重视,丘疹逐渐增多并增大至绿豆、黄豆大小,相邻的左侧大阴唇处也出现一青灰色黄豆大皮下结节.随皮损增大增多,局部疼痛感明显,并且与月经周期相一致,于2009年7月29日先后来我院妇产科和皮肤科就诊.患者平素体健,无其他疾病史,3年前有分娩时会阴侧切史,家族史无特殊.     

血管内皮生长因子和血管生成素在斑秃皮损中的表达

目的:探讨血管内皮生长因子(VEGF)和血管生成素在斑秃患者皮损处的表达情况.方法:取新鲜斑秃患者皮损和正常人头皮行冰冻切片,采用免疫组化的方法检测VEGF和血管生成素蛋白的分布和表达.结果:人毛囊的毛乳头、真皮鞘,皮脂腺等处均表达VEGF和血管生成素蛋白.斑秃患者此两种因子表达明显低于正常对照(P<0.05),且表达强度与斑秃严重程度呈负相关.结论:VEGF和血管生成素表达下调可能与斑秃的发病有关.     

血管内皮生长因子和转化生长因子β1在尖锐湿疣组织中的表达

目的:探讨血管内皮生长因子(vascularendothelialgrowthfactor,VEGF)和转化生长因子β1(transforminggrowthfactorbeta1,TGFβ1)在尖锐湿疣(condylomaacuminatum,CA)组织中的表达及其可能作用。方法:观察并定量计数27例CA病变组织的血管数,应用逆转录(RT)-PCR和免疫组化方法检测VEGF和TGFβ1的表达情况,同时以17例正常包皮组织作为对照。结果:CA组织的血管数比正常包皮组织明显增多(t=5.059,P<0.01);VEGF和TGFβ1的mRNA在CA的表达水平分别为0.880±0.054、1.136±0.145;而二者在正常包皮组织内表达水平分别为0.448±0.095、0.784±0.085(P<0.05);VEGF和TGFβ1在CA组织除角质层外的表皮全层细胞均有强表达,正常包皮组织中为弱表达,且主要位于基底层细胞;VEGF和TGFβ1的表达呈显著正相关(r=0.792,P<0.001)。结论:CA组织细胞可产生并分泌较多的TGFβ1和VEGF,两者可能与CA组织中的血管生成有关。     

Modulation of vascular endothelial growth factor receptors in melanocytes

Vascular endothelial growth factor (VEGF) is constitutively produced by keratinocytes, but has no known epidermal target cell. We now report that normal human melanocytes (Mc) maintained in serum-free, hormone-, and growth factor-supplemented medium lacking phorbol ester and choleragen constitutively express VEGF receptor-1 (VEGFR-1), VEGFR-2, and neuropilin-1. Furthermore, stimulation of Mc with VEGF165 isoform leads to phosphorylation of VEGFR-2, the receptor responsible for most of the VEGF-mediated effects in endothelial cells, suggesting that the receptor is functional. Interestingly, in Mc, VEGFR-2 expression is induced by ultraviolet irradiation and is downregulated by VEGF and tumor necrosis factor-alpha. Prolonged culture (>8 weeks) in the presence of phorbol ester abrogates VEGFR-2 expression, explaining previous reports that Mc do not express VEGFR-1 and VEGFR-2. These data suggest that VEGF may play a role in Mc behavior in skin.     

Levels of endothelial cell stimulating angiogenesis factor and vascular endothelial growth factor are elevated in psoriasis

Neovascularization appears to play an early and important part in the evolution of psoriatic plaques. We studied the distribution and production of two known angiogenesis factors, endothelial cell stimulating angiogenesis factor (ESAF) and vascular endothelial growth factor (VEGF), in the skin of patients with chronic plaque psoriasis and normal control subjects. Our results showed that tissue levels of ESAF and VEGF were significantly elevated in involved as compared with normal control skin (P = 0.006 and P < 0. 0001, respectively). Tissue levels of ESAF and VEGF were also raised in involved skin as compared with uninvolved skin in patients with psoriasis (P = 0.001 and P < 0.0001, respectively). Tissue levels of ESAF and VEGF in plaques of psoriasis correlated closely with the clinical severity of psoriasis (r = 0.6 and r = 0.9, respectively). Serum levels of ESAF and VEGF were significantly raised in patients with psoriasis as compared with control subjects (P = 0.001 and P = 0.02, respectively). In vitro culture studies revealed that ESAF is produced by both keratinocytes and fibroblasts in approximately equal quantities in normal skin, whereas VEGF is secreted predominately by keratinocytes. A similar pattern is seen in both involved and uninvolved skin of patients with psoriasis. However, there is increased secretion of both factors in keratinocytes and fibroblasts from involved and uninvolved skin as compared with normal control skin (P < 0.001). The increased levels and secretion in plaques of psoriasis of two molecules, ESAF and VEGF, known to promote new blood vessel formation, suggest a pathogenetic role for them in this disease.     

The value of blood group-specific lectin and endothelial associated antibodies in the diagnosis of vascular proliferations

Blood vascular and lymphatic tumors were evaluated immunohistochemically by studying a spectrum of endothelial associated antigens. UEA-1 lectin reacted with the tumor cells of one patient with malignant angioendothelioma in the non-metastatic stage. However, when metastasis occurred, the binding sites of this lectin completely disappeared from the surface of the tumor cells in both original and metastatic lesions, suggesting the loss of blood group H antigen from the tumor cells could be used as an indicator of metastasis in this tumor. Reaction with anti-HLA-A, B, C, intense in normal blood vessels, remained intensely positive in pyogenic granuloma and Kaposi's sarcoma, whereas it did not react with normal lymphatics and lymphangioma. This indicates that anti-HLA-A, B, C is useful in differentiating blood vascular structures from lymphatic structures in both normal and pathological conditions. OKM5 reacted intensely with benign hyperplasias in pyogenic granuloma, while barely reacting with proliferating parts in Kaposi's sarcoma, suggesting the difference in staining patterns can be used to distinguish vascular proliferation or malignancy. Reaction with anti-Type IV collagen and anti-laminin was intense in normal blood vessels, pyogenic granuloma and Kaposi's sarcoma, whereas reaction with these antibodies in normal lymphatics was patchy and irregular in its thickness.     

Expression and localization of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 in human epidermal appendages: a comparison study by immunofluorescence

Background.  Vascular endothelial growth factor (VEGF) promotes angiogenesis and plays important roles in neovascularization and development of tissues. VEGF receptors (VEGFRs) are high-affinity receptors for VEGF and are originally considered specific to endothelial cells. We have previously shown that keratinocytes from human normal skin express VEGFRs. This poses the question of whether these receptors are also expressed by epidermal appendages, as epidermal appendages are lined with epithelial cells.
Objective.  To investigate the expression of VEGFR-2 compare with VEGF in epidermal appendages, including hair follicles, eccrine sweat glands and sebaceous glands.
Methods.  Monoclonal antibodies to VEGF and VEGFR-2 were used for immunohistochemical examination of cryostat-cut sections of normal human skin specimens from 11 donors undergoing cosmetic surgery.
Results.  Immunoreactivities for VEGF and VEGFR-2 principally showed parallel intense expression in anagen hair follicle (including outer root sheat, inner root sheath, dermal papillae epidermal matrix), sebaceous glands (ductal and secretory portions) and eccrine sweat glands (ductal and secretory portions), respectively. In particular, abundant expression of VEGF was found in the follicular basement membrane zone surrounding the bulb matrix and in the ductal and secretory portions of eccrine sweat glands.
Conclusion.  A potential VEGF/VEGFR-2 autocrine pathway may be defined by the coexpression of VEGF and VEGFR-2 in human skin epidermal appendages.     

Circulating vascular endothelial growth factor in cutaneous malignant melanoma

BACKGROUND: Angiogenesis has been reported as a parameter of potential prognostic value in solid tumours, as it may facilitate tumour growth and metastasis. One of the most important growth factors involved in angiogenesis is vascular endothelial growth factor (VEGF). OBJECTIVES: To determine the predictive value of circulating VEGF levels in a cohort of patients with melanoma. METHODS: In a prospective cohort study, 324 patients with cutaneous melanoma at different clinical stages were investigated over 2 years (2002-04). VEGF was measured in plasma using enzyme-linked immunosorbent assay. Two hundred and eight patients were able to be followed up for progression of their disease and for blood sample collection (mean +/- SD follow-up 13.4 +/- 0.8 months). Data were compared with the extent of the disease and the clinical course. RESULTS: A significant increase in plasma VEGF levels was found in patients with melanoma compared with healthy controls, with statistically significant differences between patients in stages I, II and III vs. those in stage IV, but not between patients in stages I, II and III. When considering the 237 patients in stages I and II, no statistical correlation was found between plasma VEGF levels and tumour thickness. Baseline plasma VEGF levels were not significantly higher in patients who relapsed compared with nonprogressing patients. Among the 35 patients (two stage I, eight stage II and 25 stage III) who experienced a progression during follow-up, an increase in plasma VEGF level to > 100 pg mL(-1) was found in 20 (sensitivity 57.1%), while 38 of the 173 remaining nonprogressing patients demonstrated an increase in VEGF level, indicating a specificity of 78%. In addition, an increase in plasma VEGF level was found in 58 patients during follow-up, of whom 20 showed evidence of progression, indicating a positive predictive value of 34.5%. However, among the 150 remaining patients who did not demonstrate any increase in plasma VEGF level during follow-up, only 15 experienced a progression, indicating a negative predictive value of 90%. CONCLUSIONS: Our data confirm that blood VEGF levels are significantly increased in patients with melanoma and, more interestingly, that the absence of plasma VEGF level increase during follow-up appears to be associated with remission.