肝癌患者中nm23-H_1表达与转移 复发的关系

目的探讨肿瘤转移抑制因子nm23-H1基因在肝癌组织中的表达以及与转移、复发、预后的关系。方法应用免疫组织化学SP法对36例肝癌组织、30例正常组织进行nm23-H1基因蛋白检测,并追踪随访1年。结果肝癌低分化组中nm23-H1基因蛋白表达阳性率为26%,明显低于高、中分化组及正常组织(P<0.05),nm23-H1基因蛋白表达在肝内转移组明显低于无肝内转移组,两组间差异有统计学意义(P<0.01);nm23-H1基因蛋白表达在术后复发组明显低于术后无复发组。结论nm23-H1基因蛋白与肝癌的转移、复发及预后密切相关。     

乳腺肿瘤中nm23-H1、MTA1蛋白表达与癌浸润转移的关系

目的探讨nm23-H1、MTA1蛋白在乳腺肿瘤中的表达情况,研究其在乳腺癌发生、发展中的生物学意义并观察其与乳腺癌浸润及转移的内在关系。方法采用免疫组化SP法检测50例乳腺肿瘤组织中nm23-H1和MTA1蛋白的表达情况。结果乳腺浸润性导管癌组织nm23-H1蛋白阳性表达率明显低于乳腺纤维腺瘤(P<0.05);乳腺浸润性导管癌组织MTA1蛋白阳性表达率明显高于乳腺纤维腺瘤(P<0.05);乳腺肿瘤中nm23-H1和MTA1蛋白表达呈负相关(P<0.05)。结论MTA1蛋白高表达及nm23-H1蛋白低表达与乳腺癌发生浸润转移有关,二者在乳腺癌发生浸润转移过程中可能起着正负调控作用。联合检测此指标的表达状况将有助于乳腺癌的早期诊断和预后判断。     

nm23-H1和MTA1蛋白在卵巢内膜样腺癌中的表达及临床意义

目的探讨nm23-H1和肿瘤转移相关基因(MTA1)蛋白表达与卵巢内膜样腺癌之间的关系。方法运用免疫组化S-P法检测66例卵巢内模样腺癌组织中nm23-H1和MTA1蛋白的表达。结果肿瘤转移相关基因表达高低与卵巢癌-内膜样腺癌临床分期、组织学分级及淋巴结转移情况关系密切(P<0.05);nm23-H1低表达与卵巢内膜样腺癌临床分期、组织学分级及淋巴结转移关系密切(P<0.05);卵巢内膜样腺癌组织中MTA1、nm23-H1蛋白表达呈负相关(P<0.05)。结论 MTA1和nm23-H1蛋白表达与卵巢内膜样腺癌淋巴结转移、分化程度及预后关系密切,可作为卵巢内膜样腺癌患者转移复发的重要指标。     

nm23-H1、P53及COX-2与大肠癌浸润转移的关系

目的：研究76例大肠癌组织中nm23—H1、P^53及COX—2的表达与大肠癌浸润转移的关系。方法：应用免疫组化S～P法。结果：①大肠癌组织中nm23-H1的表达与大肠癌淋巴结转移相关（P〈0．05）;P^53与大肠癌分化程度、浸润深度及淋巴结转移相关（P〈0．05）;COX-2与大肠癌浸润深度及淋巴结转移相关（P〈0．05）。②大肠癌组织中nm23-H1与P^53表达呈负相关（P〈0．05,rs=-0．402）。结论：nm23-H1低表达反作用于大肠癌的转移过程,可作为预测转移的良好指标。nm23-H1、P^53及COX-2的联合检测对判断大肠癌转移和估计预后有重要价值。     

nm23-H_1基因与非小细胞肺癌转移的关系

目的探讨nm23-H1基因表达与非小细胞肺癌转移的关系。方法选择笔者所在医院2006年2月～2011年10月收治的肺癌手术患者46例,应用免疫组织化学SABC方法对46例NSCLC组织标本进行nm23-H1表达的检测。结果 46例NSCLC中nm23-H1过度表达为50%(23/46),其中鳞癌nm23-H1过度表达为47.62%(10/21),腺癌为58.33%(7/12),两者比较差异有统计学意义(P<0.05);nm23-H1的阳性表达与淋巴结转移呈负相关(P<0.01)。结论 nm23-H1可作为预测NSCLC淋巴结转移及预后的指标。     

nm23-H1——胃肠道间质瘤新的预后标记物

目的探讨nm23-H1在胃肠道间质瘤(GISTs)中的表达情况,为GISTs的预后判断提供新的病理学依据。方法应用免疫组织化学EnVision法检测nm23-H1和Ki-67在52例GISTs(转移组17例,非转移组35例)中的表达情况,对二者与Fletcher分级、临床指标及与GISTs转移的关系进行统计学分析。结果nm23-H1和Ki-67表达与Fletcher分级之间均有显著相关性(P<0.01),而与GISTs肿瘤部位及细胞类型均未见相关(P>0.05)。转移组与非转移组比较:nm23-H1阳性细胞数<50%的病例数与>50%的二组(50%～75%,>75%)之间分别比较,差异均有统计学意义(P<0.05);Ki-67增殖指数<5%的病例数与>5%的两组(5%～10%,>10%)之间比较差异有统计学意义(P<0.05)。对nm23-H1和Ki-67阳性表达例数进行统计比较,二者间有正相关关系(P<0.05)。结论nm23-H1可能是预测GISTs有无转移的有效标记物;联合检测nm23-H1和Ki-67表达,估计GISTs预后可能是一项有用指标。     

Tiam1和nm23H1在胃癌中的表达

目的探讨Tiam1和nm23H1与胃癌发生、发展过程中的相关性,从而有助于进一步探讨胃癌侵袭与转移的分子机制。方法收集胃癌标本60例,用免疫组化Max-Vision法测定Tiam1和nm23H1蛋白的表达。结果胃癌临床病理学特征与Tiam1和nm23H1表达的关系:1 Tiam1蛋白在胃癌组织中的表达水平与胃癌组织的淋巴结转移、分化程度以及浸润深度,存在显着相关性,组间比较差异具有显著性(P<0.05)。2 nm23H1蛋白在胃癌组织中的表达水平与胃癌组织的淋巴结转移、浸润深度以及分化程度存在明显相关性,组间比较差异具有显著性(P<0.05)。3 Tiam1与nm23H1蛋白表达呈负相关。结论 1 Tiam1在胃癌组织中的表达随着胃癌组织的病理分化程度的降低,淋巴结的转移,浸润深度的加深而明显增高。2 nm23H1在胃癌组织表达较低,与胃癌的浸润程度、淋巴结转移及病理分化程度有关。     

nm23—H1基因在甲状腺乳头状癌的表达及临床意义

目的：探讨nm23-H1基因在甲状腺乳头状癌的表达及其与临床病理指标的关系。方法：采用免疫组化S－P法检测201例例甲状腺乳头状癌,30例甲状腺良性增生及30例正常甲状腺组织中nm23-H1的表达情况。结果：（1）nm23-H1在甲状腺乳头状癌的表达阳性率为62．7％,明显低于两对照组（P＜0．01或P＜0．05）。（2）在甲状腺乳头状 nm23-H1在Ⅰ型、Ⅱ型、Ⅲ型间及包膜内型、腺内型、腺外型间的表达均有显著性差异。（3）有淋巴结转移组nm23-H1的阳性率为54．5％,低于无淋巴结转移组（75．0％）,其蛋白表达与颈淋巴结转移呈负相关。nm23-H1阴性表达的患者发生颈淋巴结转移的可能性大。结论：nm23-H1基因的表达与甲状腺乳状癌的发和发展、浸润和颈淋巴结转移关系密切,检测nm23-H1可作为预测甲状腺乳头状癌颈淋巴、转移肾的有价值的参考指标。     

宫颈癌组织中caspase-3与nm23-H1 基因的表达及其意义

目的探讨宫颈癌组织中caspase-3与nm23-H1基因表达的特征及相关性.方法应用免疫组织化学方法(SP法)分别检测caspase-3和nm23-H4基因在41例宫颈癌组织、17例宫颈上皮内瘤样病变(CIN)和10例正常宫颈组织中的表达,分析其与临床病理特征的相关性.结果caspase-3在宫颈癌组织和CIN中的阳性表达率均明显低于正常宫颈组织中的阳性表达率(P＜0.05);caspase-3的表达与宫颈癌的组织类型、病理分级和临床分期无相关性(P＞0.05).nm23-H4基因在宫颈癌组织中的阳性表达率与CIN及正常宫颈组织相比均具有显著性差异(P＜0.05);nm23-H1的阳性表达与宫颈癌的临床分期、组织类型、病理分级无相关性(P＞0.05).caspase-3基因的表达与nm23-H1基因的表达无相关性(P＞0.05).结论caspase-3和/或nm23-H1基因的表达降低与宫颈癌的发生密切相关.     

COX-2及nm23-H1在结直肠癌中的表达及其临床意义

目的 探讨环氧化酶2(COX-2)和肿瘤转移抑制基因H1(nm23-H1)在结直肠癌中的表达及其临床意义.方法 应用免疫组化检测COX-2、nm23-H1在62例结直肠癌中的表达.结果 COX-2的高表达与淋巴结转移、Dukes分期和浸润深度有相关性(P＜0.05);nm23-H1的低表达与分化类型、浸润深度、淋巴结转移密切相关(P＜0.05).结论 COX-2和nm23-H1的表达与结直肠癌侵袭转移密切相关,联合检测COX-2和nm23-H1有助于评估病情、判断预后和选择适当治疗手段.     

Vascular sphingosine-1-phosphate S1P1 and S1P3 receptors

The sphingolipid sphingosine-1-phosphate (S1P) acts on five subtypes of G-protein- coupled receptors, termed S1P(1) (formerly endothelial differentiation gene-1 [Edg-1]), S1P(2) (Edg-5), S1P(3) (Edg-3), S1P(4) (Edg-6) and S1P(5) (Edg-8), and possibly several other "orphan" receptors, such as GPR3, GPR6 and GPR12. These receptors are coupled to different intracellular second messenger systems, including adenylate cyclase, phospholipase C, phosphatidylinositol 3-kinase/protein kinase Akt, mitogen-activated protein kinases, as well as Rho- and Ras-dependent pathways. Consistently with this receptor multiplicity and pleiotropic signaling mechanisms, S1P influences numerous cell functions. S1P(1)1, S1P(2) and S1P(3) receptors are the major S1P receptor subtypes in the cardiovascular system, where they mediate the effects of S1P released from platelets, and possibly other tissues (such as brain). Thus S1P(1) and S1P(3) receptors enhance endothelial and vascular smooth muscle cell proliferation and migration, playing a key role in developmental and pathological angiogenesis. In contrast, S1P(2) receptors inhibit migration of these cell types, probably because of their unique stimulatory effect on a GTPase-activating protein inhibiting the activity of Rac. S1P receptors can also cause relaxation and constriction of blood vessels. The former effect is mediated by pertussis toxin-sensitive receptors (possibly S1P(1)) located on the endothelium and stimulating phosphatidylinositol 3-kinase/Akt/endothelial nitric oxide synthase (eNOS). The vasoconstricting effect of S1P is likely to be mediated by S1P(2) and/or S1P(3) receptors, via Rho-Rho-kinase, and is more potent in coronary and cerebral blood vessels. Finally, S1P also protects endothelial cells from apoptosis through activation of phosphatidylinositol 3-kinase/Akt/eNOS via S1P(1) and S1P(3) receptors. The variety of these effects, taken together with the existence of multiple receptor subtypes, provides an abundance of therapeutic targets that currently still await the development of selective agents.     

Antimykobakterielle 1-Phenyl-1-alkylaminoalkane

Antimycobacterial 1-Phenyl-1-alkylaminoalkanes Synthesis and testing for antimycobacterial properties (M. tuberculosis H 37 Ra, Middlebrook-7H9-broth) of 1-phenyl-1-alkylaminoalkanes, which differ from antimycobacterial N-alkylbenzylamines by an additional alkyl chain in α-position, is described. By variation of both alkyl chains and introduction of one or two Cl-substituents in the aromatic ring the activity increases up to an optimum within the homologous series. Overstepping optimal lipophilicity or ramification of the alkyl chains decrease activity. Compounds 19, 20, 33-35, 51-53, 61-63, 65-67, 70-73, 96 and 102 - 104 inhibit the growth of M. tuberculosis in concentrations of 2 to 4 μg/ml.     

Sulfation of iodothyronines by human sulfotransferase 1C1 (SULT1C1)*

Sulfation is an important component of human thyroid hormone metabolism. The role of the human sulfotransferase 1C1 (SULT1C1) is not known. Because SULT1C1 is present in the adult thyroid, intra-thyroidal sulfation of thyroid hormones and their metabolites might occur. We tested this hypothesis by determining the ability of recombinant human SULT1C1 to catalyze iodothyronine sulfation. Apparent K(m) values for 3,3',5-triiodothyronine (T(3)), 3, 3'-diiodothyronine (3,3'-T(2)), 3',5',3-triiodothyronine (rT(3)), and 3,3',5,5'-tetraiodothyronine (T(4)) with SULT1C1 were 28.7, 10.3, 10.2, and 59.3 microM, respectively. Thermal stability and responses to inhibitors also were tested with T(3) as the substrate. Enzyme aliquots were measured simultaneously to determine SULT1C1 substrate preferences at optimal iodothyronine concentrations. SULT1C1 activity obtained with T(3) was used as 100%, and the activities with 3,3'-T(2), rT(3), T(4), and 3,5-diiodothyronine (3, 5-T(2)) were 614, 314, 25, and 4%, respectively. We report for the first time the characterization of human SULT1C1 with T(3) and the preferences of the enzyme for various iodothyronines. The presence of SULT1C1 in the adult thyroid gland raises the possibilities that the enzyme can contribute to intraglandular thyroid hormone processing and iodide reutilization.     

Phenotype of the Cyp1a1/1a2/1b1-/- triple-knockout mouse

Crossing the Cyp1a1/1a2(-/-) double-knockout mouse with the Cyp1b1(-/-) single-knockout mouse, we generated the Cyp1a1/1a2/1b1(-/-) triple-knockout mouse. In this triple-knockout mouse, statistically significant phenotypes (with incomplete penetrance) included slower weight gain and greater risk of embryolethality before gestational day 11, hydrocephalus, hermaphroditism, and cystic ovaries. Oral benzo[a]pyrene (BaP) daily for 18 days in the Cyp1a1/1a2(-/-) produced the same degree of marked immunosuppression as seen in the Cyp1a1(-/-) mouse; we believe this reflects the absence of intestinal CYP1A1. Oral BaP-treated Cyp1a1/1a2/1b1(-/-) mice showed the same "rescued" response as that seen in the Cyp1a1/1b1(-/-) mouse; we believe this reflects the absence of CYP1B1 in immune tissues. Urinary metabolite profiles were dramatically different between untreated triple-knockout and wild-type; principal components analysis showed that the shifts in urinary metabolite patterns in oral BaP-treated triple-knockout and wild-type mice were also strikingly different. Liver microarray cDNA differential expression (comparing triple-knockout with wild-type) revealed at least 89 genes up- and 62 genes down-regulated (P-value < or = 0.00086). Gene Ontology "classes of genes" most perturbed in the untreated triple-knockout (compared with wild-type) include lipid, steroid, and cholesterol biosynthesis and metabolism; nucleosome and chromatin assembly; carboxylic and organic acid metabolism; metal-ion binding; and ion homeostasis. In the triple-knockout compared with the wild-type mice, response to zymosan-induced peritonitis was strikingly exaggerated, which may well reflect down-regulation of Socs2 expression. If a single common molecular pathway is responsible for all of these phenotypes, we suggest that functional effects of the loss of all three Cyp1 genes could be explained by perturbations in CYP1-mediated eicosanoid production, catabolism and activities.     

间质作用因子1通过正调控窖蛋白1抑制FBJ-S1-H的迁移性

目的证明间质作用因子(stromal interaction molecule1,Stim1)在FBJ诱导的小鼠骨肉瘤细胞中的抑癌作用。方法在Stim1高表达的FBJ-S1-H细胞采用Stim1以siRNA干扰技术得到Stim1沉默的几株S1-H单克隆细胞株,通过细胞行为学方法和RT-PCR技术对其mRNA进行研究,通过明胶酶谱法对细胞基质金属酶活性进行研究。结果通过细胞行为学方法证明,Stim1的沉默提高了细胞的迁移性,通过对mRNA表达的研究发现,Stim1沉默引起了多种基因表达的变化,其中包括基质金属酶9(matrix mexalloprotelnase 9,MMP-9)的升高,窖蛋白(caveolinl,Cav1),甾醇调控因子Srebf1的降低等,提高单克隆细胞中的Cav1含量可以使细胞迁移性降低。结论实验结果证明在FBJ-S1-H细胞中,Stim1能够抑制细胞的移动性,沉默Stim1的表达能够提高细胞的迁移性。