联合检测术前、术后血浆骨桥蛋白表达预测肝细胞癌切除术预后

目的:分析肝细胞癌(HCC)患者肿瘤切除术前、术后血浆骨桥蛋白(OPN)表达水平和术后转移复发及其与生存预后之间的关系,评价联合检测术前、术后血浆OPN表达在预测肝癌术后复发及预后中的作用.方法:测定56例HCC患者术前、术后血浆OPN表达水平,并收集其临床病理资料及随访资料,统计分析血浆OPN表达水平和患者术后肿瘤复发及生存预后的关系,并根据术前、术后OPN表达水平进行分组,分析其与HCC患者术后转移、复发及生存的关系.结果:术前OPN高、低表达组患者术后1年复发率分别为52.6%和24.3%(P<0.05);累积无瘤生存率为43.9%和70.5%(P<0.05);术后OPN高、低表达组患者术后1年复发率为58.3%和15.6%(P<0.01);累积无瘤生存率为36.7%和81.7%(P<0.01).联合术前、术后OPN表达对患者进行分组,高、中、低表达组患者术后1年复发率分别为70.0%、41.7%和9.1%(P<0.01);累积无瘤生存率为26.7%、54.7%和85.9%(P<0.01).术前、术后OPN单独预测1年复发的特异度分别为75.7%、72.9%,联合两指标筛选高复发风险患者的特异度为91.9%,高于相应的单个指标(P<0.05).结论:术前、术后血浆OPN表达水平与HCC患者预后相关,联合分析术前、术后OPN表达,可以筛选出更高复发风险患者.     

螺旋CT与MMP-2在肝癌复发的诊断价值

目的 探讨螺旋CT和基质金属蛋白酶2(MMP-2)在肝癌复发或转移诊断中的应用价值.方法 对82例肝癌术后的患者按预后分为复发组39例及未复发组43例,进行螺旋CT扫描及MMP-2测定,比较两组检查结果.结果 CT平扫所见病灶均为圆形或类似圆形的低密度灶,病灶直径1.1～9.6 cm.复发组MMP-2的阳性表达率为84.62%(33/39),明显高于未复发组的48.83%(21/43)(P<0.01).39例复发组中螺旋CT、MMP-2均为阳性有36例,阳性率为92.31%,明显高于未复发组的25.58%(11/43)(P<0.01).结论 螺旋CT与MMP-2在肝癌复发或转移的诊断中具有重要的意义,两者相结合判定肝癌复发或转移的价值远高于单个指标.     

肝细胞癌患者血浆MMP-2表达水平与术后复发及预后的关系

目的 回顾性分析肝细胞癌(HCC)患者血浆基质金属蛋白酶-2(MMP-2)表达水平和术后转移复发及生存预后之间的关系,评价血浆MMP-2在预测肝癌术后复发及预后中的作用.方法 应用ELISA法测定HCC病人的血浆MPP-2表达水平,统计分析血浆MMP-2表达水平和术后复发以及生存预后的关系.结果 72例HCC患者外周血浆中MMP-2平均水平为(260.18±87.18)ng/ml,MMP-2高表达组患者的1年及2年复发率明显高于低表达组患者(P=0.063,P=0.037),有末后复发的患者比无复发患者血浆MMP-2表达明显增高(P-0.042).MMP-2低表达组患者(≤260 ng/m1)的总生存(OS)时间和无瘤生存(DFS)时间均明显高于MMP-2高表达组(>260 ng/ml)(P=0.003,P=0.014),MMP-2低表达组病人的OS和DFS时间分别为(754.62±138.08)天和(627.69±230.37)天;而MMP-2高表达组病人的OS和DFS时间分别为(619.69±240.17)天和(465.86±299.48)天.应用COX回归模型进行多因素分析表明,血浆MMP-2浓度是影响肝癌患者生存和无瘤生存的一个独立危险因素(P＝0.001,P=0.004).结论 血浆MMP-2表达水平与肝细胞癌患者术后复发和生存预后密切有关,有望成为一个临床有用的预测指标.     

哮喘大鼠血管内皮生长因子表达与γ-干扰素、白介素-4变化的相关性及地塞米松的干预

目的:观察血管内皮生长因子(vascular endothelial growthfactor,VEGF)、γ-干扰素(IFN-γ)、白介素-4(IL-4)在大鼠哮喘急性模型中的表达情况,探讨Th细胞亚群的失衡与其表达的相关性.方法:36只清洁级雄性sD大鼠随机分为生理盐水对照组(C组)、哮喘组(A组)和地塞米松干预组(D组),以卵清白蛋白(ovalbumin,OVA)致敏激发法制备大鼠哮喘急性模型.末次激发24 h后腹腔注射麻醉,心脏取血,右肺行支气管肺泡灌洗留取灌洗液(BALD.应用酶联免疫吸附(ELISA)法测定血清和BALF中IL-4、IFN-γ和VEGF的浓度.结果:A组血清和BALF中IL-4、VEGF的水平均分别显著高于C组,D组血清和BALF中IL-4、VEGF的水平均分别显著低于A组(P<0.01),C组和D组相比差异均无统计学意义(P>0.05).A组血清和BALF中IFN.,的水平均显著低于C组(P<0.01),D组血清、BALF中的IFN-γ水平均显著高于A组(P<0.01)而低于C组(P<0.01).大鼠BALF中IL-4浓度与VEGF浓度呈显著正相关(r=0.797,P<0.01),IFN-γ浓度与VEGF浓度呈显著负相关(r=-0.568,P相似文献   

卵巢上皮性癌患者血清和腹水中血管上皮因子测定的临床价值

目的 测定卵巢上皮性癌患者血清和腹水中血管上皮生长因子(VEGF)的含量,探讨VEGF在卵巢上皮性癌的诊断、病情监测、预测复发中的价值.方法 采用酶联免疫吸附试验测定卵巢上皮性良性肿瘤(良性组)30例、交界性肿瘤(交界性组)7例、恶性肿瘤(恶性组)33例患者血清和腹水(或腹腔冲洗液)中VEGF的含量.结果 恶性组术前血清和腹水中VEGF的量明显高于交界性组和良性组(P＜0.05);交界性组、恶性组术后血清VEGF的量较术前明显下降(P＜0.05);恶性组Ⅲ～Ⅳ期术前血清VEGF的含量明显高于Ⅰ～Ⅱ期(P＜0.05),病理分级G2-G3的明显高于G1(P＜0.01);10例复发患者血清VEGF的含量明显高于23例未复发者(P＜0.05).结论 血清VEGF水平与卵巢上皮性癌的生长、预后有关,具有肿瘤标记物特性,可作为卵巢上皮性癌的诊断和病情监测指标.     

原发性肝癌患者血清血管内皮生长因子水平及临床意义

目的探讨原发性肝癌患者血清血管内皮生长因子(VEGF)水平与原发性肝癌患者临床病理及肿瘤侵袭转移的关系。方法应用ELISA方法对30例原发性肝癌(PHC)患者、15例肝脏良性疾病患者及15例正常人血清中VEGF水平进行检测。结果PHC组血清VEGF的含量为233.40±158.49 pg/ml,与良性肝脏疾病及正常对照组中血清VEGF的含量比较,3组间有显著性差异(P<0.01);无门脉瘤栓组患者血清VEGF含量为182.67±110.90 pg/ml,合并门脉瘤栓组患者血清VEGF含量为296.80±184.02 pg/ml,后者含量较高(P<0.05);无肝内转移组患者血清VEGF含量为194.10±131.02 pg/ml,发生肝内转移组患者血清VEGF含量为331.00±180.38 pg/ml,后者含量也较高(P<0.05);不同PHC组织VEGF表达的3组间,患者血清VEGF含量亦有显著性差异(P<0.05)。结论PHC患者血清中VEGF水平显著高于正常人和良性肝病患者;PHC患者血清VEGF水平升高是其相应组织高表达的结果;患者血清中VEGF的高表达预示着PHC的高侵袭转移能力,可以作为评估PHC转移潜能、预测患者预后的有效指标之一。     

胃切除后血清Hcy、VEGF表达水平及其影响因素的Logistic分析

目的探讨胃癌患者切除术血清同型半胱氨酸(Hcy)、血管内皮生长因子(VEGF)表达水平及其影响因素。方法选取2014年12月~2016年12月于我院行手术切除术的43例胃癌患者为研究对象,同期选取39例健康体检者为对照,利用酶联免疫吸附试验(ELISA)检测血清Hcy水平、VEGF水平。结果术前胃癌组血清Hcy、VEGF水平明显高于健康对照组,差异有统计学意义(P<0.05),术后1个月,胃癌组与健康对照组血清Hcy、VEGF水平比较,差异无统计学意义(P>0.05)。术后随访6个月,本研究43例胃癌患者中,7例复发。复发组血清Hcy、VEGF水平明显高于未复发组(P<0.05)。不同年龄、性别、肿瘤大小、肿瘤部位胃癌患者血清Hcy、VEGF水平比较,差异无统计学意义(P>0.05),不同TNM分期、分化程度、淋巴结转移胃癌患者血清Hcy、VEGF水平比较,差异有统计学意义(P<0.05)。多因素Logistic回归分析结果显示,TNM分期、淋巴结转移是影响胃癌血清Hcy、VEGF水平的独立预测因素。结论检测胃癌患者血清Hcy、VEGF水平对于病情观察、疗效观察、预后判断具有重要临床价值。     

术前血清sICAM-1和VEGF的表达水平对胃癌患者预后的判断价值

目的研究胃癌患者术前血清可溶型细胞间粘附分子-1(sICAM-1)和血管内皮生长因子(VEGF)表达与临床病理学参数、术后肿瘤复发和生存率的关系。方法运用ELISA法定量检测sICAM-1和VEGF在胃癌及正常人血清中含量。结果胃癌组术前血清sICAM-1和VEGF水平高于健康人组(P＜0.01),术后1周血清sICAM-1水平显著下降(P＜0.01),VEGF无明显变化(P＞0．05);胃癌组术前血清sICAM-1和VEGF水平,在浆膜侵及者均高于未侵及者(P＜0．05和＜0．01),在TNMⅢ期、Ⅳ期者高于TNMⅠ期、Ⅱ期者(P均＜0．01);伴淋巴结转移组血清sICAM-1水平高于不伴有淋巴结转移组(P＜0．01),血清VEGF水平与淋巴结转移状态无关(P＞0．05);胃癌组术前sICAM-1和VEGF水平高表达者容易出现肿瘤复发(P＜0．005),其二年生存率亦较低表达者低(P＜0．005);两者与患者组织学分型、性别、年龄等无关(P均＞0．05)。结论血清sICAM-1和VEGF可能参与胃癌发生、发展和侵润、转移的调控。联合检测可能有助于预测胃癌是否发生淋巴结转移及侵润程度,可作为术前判断胃癌患者预后的指标。     

PCNA、nm23在鼻腔鼻窦恶性肿瘤中的表达与肿瘤预后的关系

目的:通过检测PCNA、nm23在鼻腔鼻窦恶性肿瘤中的表达,探讨二者表达与肿瘤预后的关系。方法:用免疫组化法检测60例鼻腔鼻窦恶性肿瘤石蜡包埋组织中PCNA、nm23的表达,分析其与肿瘤的T分级、组织病理学类型、淋巴结转移和预后的关系。结果:PCNA、nm23在恶性肿瘤不同T分级和组织病理学类型组织中表达阳性率差异无统计学意义(P>0.05)。PCNA的表达在淋巴结转移组(72.00%)较未转移组(40.00%)明显增强(P<0.05),且与转移呈正相关(r=0.261,P<0.05)。而nm23的表达在转移组(40.00%)较未转移组(80.00%)明显减弱(P<0.05),且与转移呈负相关(r=-0.353,P<0.01);PCNA表达在复发组(82.35%)高于未复发组(41.86%),差异有统计学意义(χ2=8.026,P<0.01),且与复发呈正相关(r=0.366,P<0.01)。而nm23的表达在复发组(41.17%)低于未复发组(72.09%),差异有统计学意义(χ2=5.015,P<0.05),且与复发呈负相关(r=-0.289,P<0.01);不同PCNA和nm23表达水平的1年、3年和5年生存率差异无统计学意义(P>0.05)。结论:PCNA、nm23的表达可作为预测鼻腔鼻窦恶性肿瘤淋巴结转移和术后局部复发的指标,可提示肿瘤预后,并与肿瘤的T分级和组织病理学类型无关。     

人肝癌组织及外周血VEGF表达水平定量分析的临床价值

目的:定量分析肝癌(HCC)组织及血中血管内皮生长因子(VEGF)表达,并探讨其临床意义.方法:按自身配对法收集人肝癌的癌灶、癌旁及远癌组织各36份;并收集肝癌、慢性肝炎、肝硬化患者和正常对照的外周血标本181份.以免疫组化法分析肝癌组织中VEGF表达、胞内分布和临床病理学特征,并以酶联免疫吸附法对肝癌组织和血VEGF浓度进行定量分析.结果:VEGF阳性表达呈棕黄色或棕褐色,分布于肝癌细胞胞浆中;肝癌组织、HCC无包膜者和HCC伴远处转移者VEGF阳性率分别为63.9%、78.3%和90.9%,不同直径HCC间及不同分化程度HCC间VEGF阳性率差异均无统计学意义(P>0.05);肝癌组织VEGF比浓度(ng/g肝)明显高于癌旁和远癌组织(P<0.01).血VEGF如以>280 ng/L为界,肝癌、慢性肝炎、肝硬化患者及正常对照组的阳性率分别为88.4%、14.3%、10.0%和0;血VEGF与AFP联检对肝癌的诊断阳性率为94.2%.结论:VEGF是反映肝癌侵袭生长及转移的有效指标.     

Interaction of estrone and estradiol with DNA and protein of liver and kidney in rat and hamster in vivo and in vitro

[6,7-³H] Estrone (E) and [6,7-³H]estradiol-17 (E₂) have been synthesized by reduction of 6-dehydroestrone and 6-dehydroestradiol with tritium gas. Tritiated E and E₂ were administered by oral gavage to female rats and to male and female hamsters on a dose level of about 300 g/kg (54 mCi/kg). After 8 h, the liver was excised from the rats; liver and kidneys were taken from the hamsters. DNA was purified either directly from an organ homogenate or via chromatin. The radioactivity in the DNA was expressed in the units of the Covalent Binding Index, CBI = (mol chemical bound per mol DNA-P)/(mmol chemical administered per kg b.w.). Rat liver DNA isolated via chromatin exhibited the very low values of 0.08 and 0.09 for E and E₂, respectively. The respective figures in hamster liver were 0.08 and 0.11 in females and 0.21 and 0.18 in the males. DNA isolated from the kidney revealed a detectable radioactivity only in the female, with values of 0.03 and 0.05 for E and E₂, respectively. The values for male hamster kidney were < 0.01 for both hormones. The minute radioactivity detectable in the DNA samples does not represent covalent binding to DNA, however, as indicated by two sets of control experiments. (A) Analysis by HPLC of the nucleosides prepared by enzyme digest of liver DNA isolated directly or via chromatin did not reveal any consistent peak which could have been attributed to a nucleoside-steroid adduct. (B) All DNA radioactivity could be due to protein contaminations, because the specific activity of chromatin protein was determined to be more than 3,000 times higher than of DNA. The high affinity of the hormone to protein was also demonstrated by in vitro incubations, where it could be shown that the specific activity of DNA and protein was essentially proportional to the concentration of radiolabelled hormone in the organ homogenate, regardless of whether the animal was treated or whether the hormone was added in vitro to the homogenate.Carcinogens acting by covalent DNA binding can be classified according to potency on the basis of the Covalent Binding Index. Values of 10³–10⁴ have been found for potent, 10² for moderate, and 1–10 for weak carcinogens. Since estrone is moderately carcinogenic for the kidney of the male hamster, a CBI of about 100 would be expected. The actually measured limit of detection of 0.01 places covalent DNA binding among the highly unlikely mechanisms of action. Similar considerations can be made for the liver where any true covalent DNA binding must be below a level of 0.01. It is concluded that an observable tumor induction by estrone or estradiol is unlikely to be due to DNA binding.Paper presented at the Satellite Symposium of the European Society of Toxicology, Rome, March 29, 1983     

Arsenic induced changes in growth development and apoptosis in neonatal and adult brain cells in vivo and in tissue culture

Arsenic at a nonlethal level in drinking water consumed over a period of time has been reported to produce chronic toxicity and various types of health problems ranging from skin cancer to disturbance in memory. Neurotoxic effects have been reported in clinical cases with chronic exposure to arsenic. Physiological detoxication of arsenic occurs partially through methylation. Arsenic and its methylated derivatives are distributed in different organs and systems. The present study examined the possible interference in the neuronal development and differentiation due to the exposure to arsenic during gestation. The experiments were carried out to examine short and long term effects of arsenic on brain explants and cells grown and maintained in tissue culture system. The effects of arsenic exposure showed changes in brain cell membrane function indicated by generation and release of reactive oxygen-nitrogen intermediates. On the morphological aspect the explants' growth was reduced, ground matrix was lost and neural networking was inhibited. Cells showed signs of apoptotic changes. Arsenic toxicity may induce damage to brain cells prior to more visible clinical conditions. The deleterious effects also pass from the maternal to fetal tissue across the transplacental barrier.     

Nicotine metabolism and urinary elimination in mouse: in vitro and in vivo

This study aimed at elucidating the in vivo metabolism of nicotine both with and without inhibitors of nicotine metabolism. Second, the role of mouse CYP2A5 in nicotine oxidation in vitro was studied as such information is needed to assess whether the mouse is a suitable model for studying chemical inhibitors of the human CYP2A6. The oxidation of nicotine to cotinine was measured and the ability of various inhibitors to modify this reaction was determined. Nicotine and various inhibitors were co-administered to CD2F1 mice, and nicotine and urinary levels of nicotine and four metabolites were determined. In mouse liver microsomes anti-CYP2A5 antibody and known chemical inhibitors of the CYP2A5 enzyme blocked cotinine formation by 85–100%, depending on the pre-treatment of the mice. The amount of trans-3-hydroxycotine was five times higher than cotinine N-oxide, and ten times higher than nicotine N-1-oxide and cotinine. Methoxsalen, an irreversible inhibitor of CYP2A5, significantly reduced the metabolic elimination of nicotine in vivo, but the reversible inhibitors had no effect. It is concluded that the metabolism of nicotine in mouse is very similar to that in man and, therefore, that the mouse is a suitable model for testing novel chemical inhibitors of human CYP2A6.     

Circulating nucleic acids in plasma and serum: roles in diagnosis and prognosis in diabetes and cancer

The presence of DNA and RNA circulating in human plasma and serum is described. The possible sources of the DNA/RNA in blood, their ability to enter other cells and to express in the recipient cells are discussed and the relationship with metastases considered. The possible role(s) of the DNA/RNA in clinical diagnosis, in monitoring treatment and in prognosis are considered for diabetes and oncology.     

SalB stimulates neurogenesis and angiogenesis in vitro and in vivo

Aims： Previous studies suggested that Salvianolic acid B （SalB） has strong protective effect against cerebral ischemia. Recently, Sal B has been reported to enhance angiogenesis in vitro. Based on the information above, in this study we are interested in the effect of SalB on neurogenesis and angiogenesis. Methods：In vitro study, we used embryonic mouse （El6） primary cortical neural cultures. Neuron was recognized by anti-MAP2 with immunocytochemistry. Neurogenesis was tested with BrdU incorporation by ELSA method. SalB（ 10 -6 -10 -8M） or vehicle was added to the culture medium 24 hrs before BrdU addition. In vivo, middle cerebral artery occlusion （MCAO） rats were used as focal cerebral ischemia model.     

Metabolic interaction between imipramine and carbamazepine in vivo and in vitro in rats

Summary The pharmacokinetic consequences of the combination of carbamazepine with imipramine in male Wistar rats have been investigated. It was found that a 2-week treatment with the combination resulted in the increase of the concentrations of the parent compounds and a simultaneous decrease in their metabolites in blood plasma i.e. carbamazepine inhibited imipramine demethylation in the side chain while imipramine inhibited carbamazepine 10,11-epoxidation. The velocity of imipramine 2-hydroxylation and 10,11-epoxy-carbamazepine hydration did not seem to be changed by the combination. On the basis of studies in vitro it is concluded that the observed metabolic interaction between carbamazepine and imipramine is due to the competition of the drugs for the active centre of cytochrome P 450 and to a certain qualitative alteration of the enzyme by imipramine as can be deducted from the decrease of carbamazepine binding to the cytochrome. Send offprint requests to K. J. Netter     

Nicotine metabolism and urinary elimination in mouse: in vitro and in vivo

This study aimed at elucidating the in vivo metabolism of nicotine both with and without inhibitors of nicotine metabolism. Second, the role of mouse CYP2A5 in nicotine oxidation in vitro was studied as such information is needed to assess whether the mouse is a suitable model for studying chemical inhibitors of the human CYP2A6. The oxidation of nicotine to cotinine was measured and the ability of various inhibitors to modify this reaction was determined. Nicotine and various inhibitors were co-administered to CD2F1 mice, and nicotine and urinary levels of nicotine and four metabolites were determined. In mouse liver microsomes anti-CYP2A5 antibody and known chemical inhibitors of the CYP2A5 enzyme blocked cotinine formation by 85-100%, depending on the pre-treatment of the mice. The amount of trans-3-hydroxycotine was five times higher than cotinine N-oxide, and ten times higher than nicotine N-1-oxide and cotinine. Methoxsalen, an irreversible inhibitor of CYP2A5, significantly reduced the metabolic elimination of nicotine in vivo, but the reversible inhibitors had no effect. It is concluded that the metabolism of nicotine in mouse is very similar to that in man and, therefore, that the mouse is a suitable model for testing novel chemical inhibitors of human CYP2A6.     

Pharmacokinetic and pharmacogenetic determinants and considerations in chemotherapy selection and dosing in infants

INTRODUCTION: There is a lack of high-quality data regarding optimal chemotherapy dosage regimens among infants. Dosing regimens for chemotherapy during the first year of life are commonly based on empiric recommendations extrapolated from older children; however, balancing efficacy and toxicity is critical as severe adverse drug reactions may lead to treatment failure or reduced adherence to needed medications. AREAS COVERED: This review describes pharmacokinetic and pharmacogenetic considerations when administering chemotherapeutic agents to infants. Examples of commonly used agents are provided with practical recommendations for dosing adjustments. EXPERT OPINION: Optimal chemotherapy for children and infants in particular has lagged behind the remarkable progress in cancer treatment and it is clear that far more basic and clinical research are needed with respect to the mechanistic basis of age-dependent differences in pharmacokinetic parameters. More recent studies which have combined pharmacokinetic data with clinical toxicity and outcome data have resulted in a number of more evidence-based guidelines at least for the initial chemotherapy dosing; however, at present, the dosing of chemotherapy drugs in neonates and infants remains largely empiric.     

Consistency in catecholamine and cortisol excretion in males and females

Data from a series of experiments performed on 24 female and 24 male subjects were used to evaluate the consistency in urinary catecholamine and cortisol excretion. Data were available from 8 laboratory situations of varying activity level and content, spaced at intervals of maximum 3 months. Correlational analyses showed that for cortisol, interindividual consistency was higher for measures obtained on the same day than for measures obtained on different days. Interindividual consistency was generally high in catecholamine and cortisol excretion during non-stressful situations in both sexes. During experimental stress, however, consistency was as high as during nonstress for males, while it was lower for females. Analysis of variance components confirmed these results and showed that in males variation due to interindividual differences was high during both baseline and experimental-stress situations, while in females it was high during baseline situations only. During experimental stress, variation for females was due primarily to interaction. It is suggested that the males showed a more generalized stress response over situations than the females.     

Penetration and action of edoxudine in vitro and in vivo

The penetration of 5-ethyl-2'-deoxyuridine (edoxudine, Aedurid) from gel base with and without the addition of urea and other adjuvant has been studied in an in vitro model using guinea pig skin. The formulation of 3% edoxudine gel with 5% urea showed the best results. In vivo experiments on hairless mice infected intracutaneously with herpes simplex virus type 1 also showed this formulation's good efficacy as compared to other formulations.