缺氧诱导因子1 α、血管内皮生长因子和成纤维细胞生长因子在胰腺癌中的表达及意义

目的:研究胰腺癌组织中缺氧诱导因子la|pha(Hypoxia-inducible factor-laipha,HIF-1α)、血管内皮生长因子(vascular endothelial growth factor,VEGF)和成纤维细胞生长因子(fibroblast growth factor,FGF)的表达并探讨其意义.方法:Western blot法检测22例胰腺癌及癌旁组织中HIF-1α、VEGF和FGF蛋白的表达,分析HIF-1α与VEGF、FGF之间的相关性以及与性别、年龄、肿瘤大小、淋巴结转移和TNM分期之间的关系.结果:HIF-1α、VEGF和FGF在胰腺癌组织中的蛋白表达水平明显高于胰腺癌周组织(P＜0.01),HIF-1α与VEGF、FGF之间的表达具有显著相关性(P＜0.01).HIF-1α的表达与胰腺癌的TNM分期、肿瘤大小和淋巴结转移有关(P＜0.01),VEGF和FGF的表达与胰腺癌的肿瘤大小和淋巴结转移有关(P＜0.05).结论:HIF-1α可以上调VEGF和FGF的表达,在胰腺癌的发生、发展中起着重要作用.     

VEGF、HIF-1α、Vasohibin在子宫内膜腺癌血管生成中的作用及与预后的关系

目的通过研究血管内皮生长因子(vascular endometrial growth factor,VEGF)、缺氧诱导因子1α(hypoxia-inducible factor-1α,HIF-1α)和vasohibin在正常子宫内膜(normal endometrium,NE)和子宫内膜样腺癌(endom-etrioid adenocarcinoma,EA)组织中的表达,探讨上述指标与间质微血管密度(microvessel density,MVD)、EA临床病理特性及预后的关系。方法采用免疫组化Envision二步法检测105例EA和20例NE组织中VEGF、HIF-1α、vasohibin和MVD的表达。分析各指标相互之间及与EA临床病理特性和预后间的关系。结果(1)EA组中,VEGF、HIF-1α和MVD的表达明显高于NE组(P0.05),vasohibin的表达明显低于NE组(P0.01)。(2)VEGF、HIF-1α和MVD的表达与EA的手术病理分期相关(P0.05)。(3)在EA组,除vasohibin外,VEGF、HIF-1α和MVD三者的表达量两两间均呈正相关(P0.05)。(4)98例有完整随访资料患者的5年生存率为87.8%,VEGF、HIF-1α及vasohibin表达阳性组与阴性组5年生存率无显著性差异;MVD高表达组5年生存率明显低于MVD低表达组(P0.05)。结论异常增生的微血管与EA发生、发展及预后有关。VEGF、HIF-1α、vasohibin三者间动态平衡的失调促进了EA组织中的微血管生成,重建三者间的正常调节关系,刺激vasohibin的表达,可能是EA治疗的一个靶点。     

稽留流产患者血清和绒毛中HIF-1α和VEGF表达水平及其相关性分析

目的:探讨缺氧诱导因子-1α(HIF-1α)和血管内皮生长因子(VEGF)在稽留流产患者血清和绒毛中的表达水平及其相关性分析。方法:选择2014年8月至2015年8月我院妇产科76例稽留流产患者为观察组及行人工流产的60例正常早产孕妇为对照组;根据患者稽留流产时间将稽留流产患者分为稽留时间2周组(12例),2~4周组(33例),4周组(31例);采用酶联免疫吸附(ELISA)和免疫组化SP法检测并分析患者血清与绒毛中HIF-1α与VEGF的表达水平。结果:观察组血清中HIF-1α与VEGF表达水平均显著低于对照组,差异有统计学意义(P0.05);观察组和对照组绒毛VEGF和HIF-1α均表达,其中VEGF主要表达于滋养层细胞细胞质和细胞间质,HIF-1α主要表达于滋养层细胞的细胞核与细胞质,且观察组患者绒毛HIF-1α与VEGF表达水平均显著低于对照组,差异有统计学意义(P0.05);不同稽留时间患者绒毛HIF-1α与VEGF表达水平间比较,差异均无统计学意义(P0.05)观察组患者血清HIF-1α与VEGF的表达水平呈现正相关关系(r=0.601;P0.05);且绒毛HIF-1α与VEGF的表达水平也呈现正相关关系(r=0.401;P0.05)。结论:HIF-1α和VEGF在血清和绒毛中的低表达可能是稽留流产的发生的重要原因,临床上可以通过检测患者血清和绒毛组织中HIF-1α和VEGF的水平,有针对性的对患者进行监护和治疗,预防稽留流产的发生。     

2-甲氧基雌二醇对乳腺癌MCF-7细胞HIF-1α、CXCR4、VEGF表达的影响

目的:探讨2-甲氧基雌二醇(2-Methoxyestradiol,2ME2)对乳腺癌MCF-7细胞生长及缺氧诱导因子-1α(Hypoxia-inducible factor1 α,HIF-1α)、趋化因子受体-4(CXC chemokine receptor-4,CXCR4)、血管内皮生长因子(Vascular endothelial growth factor,VEGF)表达的影响.方法:采用MTT法检测不同浓度2ME2对MCF-7细胞的增殖抑制作用;Hoechest 33258染色观察细胞凋亡形态学改变;RT-PCR、Western blot分别检测不同浓度2ME2对乳腺癌MCF-7细胞中HIF-1α、CXCR4、VEGF mRNA及蛋白表达水平的影响.结果:2ME2可较强的抑制MCF-7细胞增殖,并呈时间和剂量依赖性;经2ME2作用48h后MCF-7细胞表现出典型的凋亡形态特征;不同浓度2ME2作用于MCF-7细胞48小时后,随着药物浓度的增加细胞中HIF-1α、CXCR4、VEGF在mRNA及蛋白表达水平逐渐降低,与对照组相比有统计学意义(P＜0.05).结论:2ME2可通过降低HIF-1α、CXCR4、VEGFmRNA及蛋白表达,抑制乳腺癌MCF-7细胞的增殖及肿瘤血管生成和侵袭转移相关因子的表达.     

TGF-β1、HIF-1α、VEGF在胃癌组织及癌旁组织中的表达及临床意义

目的：研究TGF-β1（转化生长因子-β1）、HIF-1α（低氧诱导因子-1α）、VEGF（血管内皮生长因子）在胃癌组织及癌旁组织中的表达及临床意义。方法：选取于我院就诊的160例胃癌手术患者切除的组织,采用免疫组化技术检测手术切除的胃癌组织中的TGF-β1、HIF-1α及VEGF的表达,分析其与患者临床病理参数的关系。结果：免疫组化结果显示：TGF-β1、HIF-1α及VEGF在胃癌组织中的表达均高于癌旁组织,差异均有统计学意义（P〈0.05）;TGF-β1、HIF-1α及VEGF的表达均与肿瘤分期、淋巴结转移及浸润深度有关（P〈0.05）;VEGF的表达分别与TGF-β1、HIF-1α的表达呈相关关系（P〈0.05）。结论：TGF-β1、HIF-1α及VEGF在胃癌组织中的表达与胃癌的病理学特征有关,检测TGF-β1、HIF-1α及VEGF的表达将有助于临床诊治胃癌患者。     

缺氧诱导因子1α、血管内皮生长因子和成纤维细胞生长因子在胰腺癌中的表达及意义

目的：研究胰腺癌组织中缺氧诱导因子1alpha（Hypoxia-inducible factor-1alpha,HIF-1α）、血管内皮生长因子（vascular endothelial growth factor,VEGF）和成纤维细胞生长因子（fibroblast growth factor,FGF）的表达并探讨其意义。方法：Western blot法检测22例胰腺癌及癌旁组织中HIF-1α、VEGF和FGF蛋白的表达,分析HIF-1α与VEGF、FGF之间的相关性以及与性别、年龄、肿瘤大小、淋巴结转移和TNM分期之间的关系。结果：HIF-1α、VEGF和FGF在胰腺癌组织中的蛋白表达水平明显高于胰腺癌周组织（P〈0.01）,HIF-1α与VEGF、FGF之间的表达具有显著相关性（P〈0.01）。HIF-1α的表达与胰腺癌的TNM分期、肿瘤大小和淋巴结转移有关（P〈0.01）,VEGF和FGF的表达与胰腺癌的肿瘤大小和淋巴结转移有关（P〈0.05）。结论：HIF-1α可以上调VEGF和FGF的表达,在胰腺癌的发生、发展中起着重要作用。     

益气活血解毒中药联合奥沙利铂对晚期肝癌AFP, VEGF的影响

目的:探讨益气活血解毒中药联合奥沙利铂治疗晚期肝癌的临床疗效。方法:选择在我院接受治疗的晚期肝癌患者56例,随机分为对照组和观察组,每组28例。对照组患者采用奥沙利铂栓塞治疗,观察组患者采用奥沙利铂栓塞联合益气活血解毒中药治疗。观察并比较两组患者治疗前后血清缺氧诱导因子-1α(HIF-1α)、甲胎蛋白(AFP)、脯氨酸羟化酶2(PHD2)、血管内皮生长因子(VEGF)水平的变化情况以及临床总有效率。结果:与治疗前相比,两组治疗后患者血清AFP,VEGF,HIF-1α及PHD2水平均降低,差异具有统计学意义(P0.05);与对照组比较,观察组患者治疗后血清AFP,VEGF,HIF-1α及PHD2水平较低,差异具有统计学意义(P0.05);观察组临床总有效率(92.59%)高于对照组(71.43%),差异具有统计学意义(P0.05)。结论:益气活血解毒中药联合奥沙利铂能够降低肝癌晚期患者血清AFP,VEGF,HIF-1α及PHD2水平,提高临床疗效。     

术前血清VEGF、HMGB1及HIF-1α对无法切除的肝细胞癌患者TACE术后预后的预测价值

摘要 目的：探讨术前血清血管内皮生长因子（VEGF）、高迁移率族蛋白B1（HMGB1）及缺氧诱导因子-1α（HIF-1α）对无法切除的肝细胞癌（HCC）患者经动脉化疗栓塞（TACE）术后预后的预测价值。方法：选取2018年6月～2021年6月湖南中医药高等专科学校附属第一医院收治的240例无法行根治性切除术的HCC患者,根据TACE术后1年预后情况分为预后不良组和预后良好组。采用酶联免疫吸附法检测术前血清VEGF、HMGB1及HIF-1α水平,分析三者与HCC患者临床病理特征的关系。采用多因素Logistic回归分析HCC患者TACE术后预后不良的影响因素,采用受试者工作特征（ROC）曲线分析术前血清VEGF、HMGB1及HIF-1α水平对HCC患者TACE术后预后不良的预测价值。结果：HCC患者术前VEGF、HMGB1及HIF-1α水平与Child-Pugh分级、分化程度和血管侵犯有关（P＜0.05）。随访1年,240例HCC患者TACE术后预后不良发生率为25.42％（61/240）。多因素Logistic回归分析显示,Child-Pugh分级B级、甲胎蛋白≥400 μg/L、血管侵犯和VEGF、HMGB1、HIF-1α升高为HCC患者TACE术后预后不良的独立危险因素（P＜0.05）。ROC曲线分析显示,术前血清VEGF、HMGB1及HIF-1α水平联合预测HCC患者TACE术后预后不良的曲线下面积大于VEGF、HMGB1、HIF-1α单独预测。结论：术前血清VEGF、HMGB1及HIF-1α水平升高与HCC患者TACE术后预后不良有关,三者联合预测HCC患者TACE术后预后不良的价值较高。     

HIF-2α、VEGF在子宫颈鳞癌组织中的表达及其临床意义

目的检测宫颈鳞癌组织及正常宫颈组织中HIF-2α、VEGF基因与蛋白的表达情况,探讨其在子宫颈鳞癌的临床意义。方法随机选取64例子宫颈鳞癌组织和22例正常宫颈组织,收集年龄、FIGO分期和淋巴结转移等临床相关指标,采用实时荧光定量PCR法及免疫组织化学法(Elivision法)检测各组织中HIF-2α、VEGF的表达。结果实时荧光定量PCR分析结果表明HIF-2α、VEGF mRNA表达较正常宫颈组织显著增加,差异有统计学意义(P0.05),且二者mRNA水平呈正相关(r=0.778,P0.001)。免疫组织化学法结果表明HIF-2α、VEGF蛋白在宫颈组织中的阳性表达率分别为宫颈鳞癌组93.8%、正常宫颈组18.2%,两组比较差异有统计学意义,且HIF-2α与VEGF呈显著相关(r=0.514,P0.05)。HIF-2α、VEGF的mRNA表达均与年龄无关,但与FIGO分期、淋巴结转移关系密切(P0.05),FIGO分期高、有淋巴结转移的子宫颈癌组织HIF-2α、VEGFmRNA表达水平均相应对照组升高。结论与正常宫颈组织相比,HIF-2α、VEGF mRNA和蛋白在宫颈鳞癌中均呈高表达。     

幽门螺杆菌感染对胃癌治疗靶基因表达的影响

胃癌发病及进展机制与多种致癌因素有关,其中幽门螺杆菌(Helicobacter pylori, Hp)的感染是不可或缺的因素。近年来,越来越多的胃癌靶向及免疫治疗靶点被发现,其中人表皮生长因子受体2(human epidermal growth factor receptor, HER-2)、表皮生长因子受体(epithelial growth factor receptor, EGFR)、血管内皮生长因子(vascular endothelial growth factor, VEGF)、程序性死亡配体-1(programmed death ligand-1, PD-L1)作为癌症靶向治疗和免疫治疗常见的靶基因,在胃癌中的异常表达与Hp感染间的密切关系已逐渐被人们所认识。现就Hp感染诱导靶向治疗和免疫治疗相关靶基因异常表达的作用机制作一概述,旨在为Hp感染的胃癌患者靶向治疗和免疫治疗方案的制定提供新的思路。     

Definitions,measurements, and classifications of stimuli,situations, and environments

A review is presented of issues relevant to the definition, measurement, and classification of stimuli, situations, and environments. Problems such as the lack of adequate definitions of concepts, error and bias in measurement procedures, confusion between measurement of a concept and measurement of its behavioral effects, and the lack of agreement among alternative measures are emphasized. It is suggested that concepts be defined in terms of objective characteristics while allowing for the study of the transactional relationship between organism and environment. The work of the ethologists in defining stimuli while studying their relationship to different organismic states and situational contexts is emphasized in this regard. Following Brunswik, it is also suggested that wherever possible there be a representative sampling of variables in natural settings. Note from the editors: From time to time, Human Ecology will publish a review article. Our first in this series is a review by a psychologist of basic definitional and conceptual problems in environmental studies.This paper was prepared while the author was a Visiting Research Fellow at the Educational Testing Service. The support of ETS and my colleagues in the Division of Psychological Studies is gratefully acknowledged. The review was also supported in part by a grant from the Rutgers University Research Council.     

Synthesis,tautomerism, and antimicrobial,anti-HCV,anti-SSPE,antioxidant, and antitumor activities of arylazobenzosuberones

2-Dimethylaminomethylene-1-benzosuberone 1 was coupled with diazotized aniline derivatives to afford a series of the hitherto unreported 2-arylazo-1-benzosuberones 3a–i. The tautomeric structure and the effect of substituents on the tautomeric form (s) of the products 3a–i were discussed. Similar coupling of the enaminone 1 with diazonium salts of heterocyclic amines gave the respective fused azolotriazino-benzosuberones. Some of the newly synthesized compounds showed potent antimicrobial, anti-HCV, antioxidant, antitumor (as topoisomerase I inhibitors), and antimicrobial activities.     

The effect of malathion,diazinon, and various concentrations of zinc,copper, nickel,lead, iron,and mercury on fish

Acute and chronic toxicity tests for malathion, diazinon, copper (Cu), mercury (Hg), lead (Pb), zinc (Zn), nickel (Ni), and iron (Fe) were conducted. Mortalities ofBarilius vagra andCyprinus carpio (common carp) were variable but LC50-96 hr were similar for pesticides. AdultB. vagra seem to be more sensitive to malathion than juvenile carp. Both juvenile carp and adultB. vagra were extremely sensitive to diazinon. Long-term exposure to pesticides modified morphology and behavior. The LC50-96 values for Cu, Hg, and Pb were 0.3, 0.16, and 0.44, respectively, for smaller fish and 1.0, 0.77, and 1.33, respectively, for larger fish. Replicate LC50 values for Zn, Ni, and Fe were somewhat variable, and for these metals, the size of the fish seemed to affect response because LC50 values increased as fish size increased. Cooper, Pb, Zn, and Fe residues following exposure to sublethal concentrations of these metals for 15 d were significantly greater in whole juvenile common carp than in controls.     

Synthesis and properties of N-, O-, and S-phospho derivatives of amino acids, peptides, and proteins

The literature on chemical (i.e., nonenzymic) phosphorylation of amino acids, peptides, and proteins is reviewed through 1982. The review covers synthetic methods, chemical reactions, and physical properties, with emphasis on the techniques used for separation and characterization of the products. Synthetic methods are classified by reagent rather than product, and are illustrated by experimental procedures for the most important methods. Chemical reactions are classified into four groups depending on whether the reaction site is the phospho group, the amino group, the carboxyl group, or in the case of serine the hydroxyl group. Physical data are given for all of the known N-, O-, and S-phospho derivatives of the amino acids, peptides, and proteins, within certain limitations, and are discussed in detail in the section on physical properties. Emphasis is given to the techniques used for separation of the products, such as chromatography and electrophoresis, and for characterization of the products, particularly spectroscopy. Medical and other uses of the products are mentioned.     

Low-frequency dynamics and Raman scattering of crystals, of B-, A-, and Z-DNA, and fibers of C-DNA

Normal modes of vibration of DNA in the low-frequency region (10-300 cm-1 interval) have been identified from Raman spectra of crystals of B-DNA [d(CGCAAATTTGCG)], A-DNA [r(GCG)d(CGC) and d(CCCCGGGG)], and Z-DNA [d(CGCGCG) and d(CGCGTG)]. The lowest vibrational frequencies detected in the canonical DNA structures--at 18 +/- 2 cm-1 in the B-DNA crystal, near 24 +/- 2 cm-1 in A-DNA crystals, and near 30 +/- 2 cm-1 in Z-DNA crystals--are shown to correlate well with the degree of DNA hydration in the crystal structures, as well as with the level of hydration in calf thymus DNA fibers. These findings support the assignment [H. Urabe et al. (1985) J. Chem. Phys. 82, 531-535; C. Demarco et al. (1985) Biopolymers 24, 2035-2040] of the lowest frequency Raman band of each DNA to a helix mode, which is dependent primarily upon the degree of helix hydration, rather than upon the intrahelical conformation. The present results show also that B-, A-, C-, and Z-DNA structures can be distinguished from one another on the basis of their characteristic Raman intensity profiles in the region of 40-140 cm-1, even though all structures display two rather similar and complex bands centered within the intervals of 66-72 and 90-120 cm-1. The similarity of Raman frequencies for B-, A-, C-, and Z-DNA suggests that these modes originate from concerted motions of the bases (librations), which are not strongly dependent upon helix backbone geometry or handedness. Correlation of the Raman frequencies and intensities with the DNA base compositions suggests that the complex band near 90-120 cm-1 in all double-helix structures is due to in-plane librational motions of the bases, which involve stretching of the purine-pyrimidine hydrogen bonds. This would explain the centering of the band at higher frequencies in structures containing G.C pairs (greater than 100 cm-1) than in structures containing A.T pairs (less than 100 cm-1), consistent with the strengths of G.C and A.T hydrogen bonding.     

Synthesis,spectroscopic, and antibacterial activity of tetraazamacrocyclic complexes of trivalent chromium,manganese, and iron

A new series of macrocyclic complexes of type [M(TML)X]X₂, where M = Cr(III), Mn(III), or Fe(III), TML is tetradentate macrocyclic ligand, and X = Cl^?, NO₃^?, CH₃COO^? for Cr(III), Fe(III) and X = CH₃COO^? for Mn (III), has been synthesized by condensation of benzil and succinyldihydrazide in the presence of metal salt. The complexes have been so formulated due to the 1:2 electrolytic nature of these complexes as shown by conductivity measurements. The complexes have been characterized with the help of various physicochemical techniques such as elemental analysis, molar conductance, electronic and infrared spectral studies, and magnetic susceptibility. On the basis of these studies, a five-coordinate distorted square pyramidal geometry, in which two nitrogens and two carbonyl oxygen atoms are suitably placed for coordination toward the metal ion, has been proposed for all the complexes. The complexes have been tested for their in vitro antibacterial activity. Some of the complexes show remarkable antibacterial activities against some selected bacterial strains. The minimum inhibitory concentrations shown by these complexes have been compared with those shown by some standard antibiotics such as linezolid and cefaclor.