乳腺癌组织蛋白酶D、c-erbB-2、P53、P16、nm23蛋白表达与淋巴结转移的关系

目的:探讨乳腺癌组织蛋白酶D(Cath-D)、c-erbB-2、P53、P16、nm23蛋白的表达与淋巴结转移的关系。方法:应用免疫组织化学S-P法,检测100例乳腺癌Cath-D、c-erbB-2、P53、P16、nm23蛋白的表达情况。结果:Cath-D、c-erbB-2、P53、P16、nm23蛋白阳性表达率分别为61%、55%、60%、47%、58%。有腋窝淋巴结转移患者的Cath-D、c-erbB-2、P53阳性表达率明显高于无转移者(P<0.01),有腋窝淋巴结转移患者的P16、nm23蛋白阳性表达率明显低于无转移者(P<0.01)。结论:Cath-D、c-erbB-2、P53的高表达与P16、nm23蛋白的低表达可能促进乳腺癌的淋巴结转移,联合检测以上生物学指标有助于提高对乳腺癌预后评价和治疗的正确性。     

大肠癌nm23、p53、CerbB-2基因表达与淋巴结转移的关系

目的探讨大肠癌nm23、p53、CerbB-2基因表达与淋巴结转移的关系。方法采用免疫组织化学Envision法检测84例大肠癌组织中的nm23、p53、CerbB-2的表达。结果大肠癌中nm23、p53、CerbB-2的阳性表达分别是41.7%、64.3%、59.5%。nm23阴性、p53、CerbB-2阳性者淋巴结转移率分别是89.8%、85.2%、88.0%,均高于nm23阳性、p53、CerbB-2阴性者淋巴结转移率(57.1%、53.3%、58.8%),差异有显著性(P<0.01)。同时有两个及以上指标表达异常者淋巴结转移率为84.0%,高于一个指标表达异常或三个指标均不表达异常者淋巴结转移率(64.7%),差异有显著性(P<0.05)。结论nm23、p53、CerbB-2在大肠癌中的表达与大肠癌淋巴结转移密切相关,nm23、p53、CerbB-2的表达在大肠癌淋巴结转移中可能起协同作用,可作为临床检测转移和估计预后的重要指标。     

nm23、C-erbB-2和p53蛋白表达对乳腺癌预后的多因素分析

【目的】探讨乳腺癌组织中nm23、C-erbB-2和p53基因蛋白表达及其与临床病理指标和预后的关系。【方法】应用免疫组化S-P方法检测157例乳腺癌石蜡切片中nm23、C-erbB-2和p53蛋白的表达;应用Kaplan-Meier法及多变量Cox比例风险模型分析3种蛋白表达与预后的关系。【结果】①nm23表达率为58．0％,与肿瘤大小、TNM分期、腋淋巴结状态和远处转移有关;C-erbB-2表达率为40．8％,与患者年龄、月经状况、肿瘤大小、TNM分期和腋淋巴结状态相关;p53表达率为42．7％,与TNM分期和腋淋巴结状态及远处转移有关;②nm23阳性表达与C-erbB-2阳性表达呈负相关,与p53阳性表达呈正相关;C-erbB-2阳性表达与p53阳性表达呈负相关;③nm23阳性组生存率高于阴性组;C-erbB-2阳性组生存率低于阴性组;p53阳性组生存率高于阴性组;④多因素Cox回归分析显示,nm23、C-erbB-2不同表达及TNM分期3项指标反映乳腺癌预后情况,危险度分别为0．395、2．009及1.446。【结论】nm23、C-erbB-2表达和TNM分期是乳腺癌的独立的预后指标,检测nm23、C-erbB-2有助于筛选出具有高复发及转移危险的患者。     

beclin-1、LC3及ki67在青年女性乳腺癌中的表达及临床意义

目的研究beclin-1、LC3以及ki67在青年女性乳腺癌中的表达及临床意义。方法临床纳入2008年1月至2015年12月乳腺癌青年女性(35岁)患者121例作为研究组。另选取133例同期乳腺癌中老年女性(≥35岁)患者作为对照组。使用免疫组织化学法对两组患者标本进行检测,观察beclin-1、LC3以及ki67的表达情况。结果研究组患者TNM分期与对照组对比差异有统计学意义(P0.05)。研究组腋窝淋巴结转移≥4个的89例(73.55%),明显高于对照组的68例(51.13%,P0.05)。观察组beclin-1、LC3阳性表达率明显低于对照组,ki67高表达率明显高于对照组(均P0.05)。beclin-1、LC3、ki67表达情况与TNM分期以及腋窝淋巴结转移相关,且TNM分期越高,腋窝淋巴结转移数目越多,beclin-1、LC3阳性表达率越低,ki67高表达率越高。结论青年女性乳腺癌组织中beclin-1以及LC3表达阳性率明显较低,ki67表达水平明显较高,与淋巴结转移数目和TNM分期有关,可有效预测患者淋巴结转移风险。     

p53过表达、nm23低表达与卵巢癌浸润、转移关系的探讨

目的探讨p53、nm23与卵巢上皮性恶性肿瘤的发生、发展和转移的关系。方法应用LSAB免疫组化染色方法检测p53和nm23的表达。结果p53和nm23在良性、交界性、卵巢癌Ⅲ期及Ⅳ期各组中的表达率分别为0、0、45%、46%和40%、40%、55%、23%。nm23在卵巢癌Ⅲ期有淋巴结转移组的表达率为18%(5/28),较无淋巴结转移组83%(10/12)明显低(P<0.01);p53在无淋巴结转移组的表达率50%(6/12)与有淋巴结转移组40%的差异不显著(11/28)(P>0.05)。结论提示p53过表达与卵巢癌的浸润和增殖有关,与淋巴结转移无关。nm23低表达在卵巢癌的转移中起重要作用,与癌组织表面的种植及局部扩散关系不密切。     

Ki-67、P53在乳腺癌腋窝淋巴结转移中的表达与意义

目的探讨Ki-67、P53在Her-2阴性乳腺癌腋窝淋巴结转移中的表达及临床意义。方法选取收治的60例Her-2阴性浸润性乳腺癌患者的临床资料,根据ER表达分为阴性组28例与阳性组32例,研究Ki-67、P53在Her-2阴性乳腺癌组织中的表达及与ER、腋窝淋巴结转移的相关性。结果 ER阳性组乳腺癌组织中Ki-67增殖指数、P53表达明显低于阴性组(P0.05),腋窝淋巴结阳性组中Ki-67增值指数、P53表达明显高于淋巴结阴性组(P0.05)。结论Ki-67增殖指数、P53表达在Her-2阴性乳腺癌组织中与ER阴性呈正相关,且Ki-67增殖指数与腋窝淋巴结转移可能性大,由此提示P53、Ki-67可是Her-2阴性乳腺癌不良预后的相关因素。     

nm23基因表达对乳腺癌患者生存期等预后指标的影响

目的:探讨nm23基因表达对乳腺癌患者预后的影响。方法:选择哈尔滨医科大学附属第二医院普外科1997-06/1998-12行根治性治疗的乳腺癌患者60例。均为女性,年龄2663岁。有腋淋巴结转移30例,无腋淋巴结转移30例。依国际抗癌协会临床分期标准,Ⅰ期30例,Ⅱ期16例,Ⅲ期14例,无Ⅳ期患者。随机选取同期乳腺囊性增生症患者20例作对照。应用免疫组织化学SP法检测两组患者标本中nm23基因的表达情况,观察nm23阳性表达与临床病理参数、远处转移及生存率的关系。nm23基因表达以细胞浆呈棕黄色为阳性。结果:乳腺癌患者60例,乳腺囊性增生症患者20例,均进入结果分析。①nm23基因在乳腺癌及乳腺囊性增生症中的阳性表达:乳腺癌中nm23阳性表达显著高于乳腺囊性增生症中nm23阳性表达(60.0%,30.0%,P<0.05)。②nm23阳性表达与临床病理参数的关系:临床Ⅰ～Ⅱ期患者nm23阳性表达率著性高于Ⅲ期患者(67.4%,35.7%,P<0.05);无淋巴结转移者nm23的阳性表达率显著高于有淋巴结转移者(86.7%,33.3%,P<0.05);雌激素受体(+)者nm23的阳性表达率显著高于雌激素受体(-)者(72.7%,25.0%,P<0.05);孕激素受体(+)者nm23的阳性表达率显著高于孕激素受体(-)者(75.0%,30.0%,P<0.05)。③nm23阳性表达与远处转移及生存率的关系:无远处转移者nm23的阳性表达率显著高于有远处转移者(73.4%,14.3%,P<0.05);nm23阳性表达者5年生存率显著高于nm23阴性表达者(94.4%,50.0%,P<0.05)。结论:检测乳腺癌组织中nm23基因对评价乳腺癌患者的预后和指导临床治疗有重要价值。     

p53蛋白、ki-67抗原和表皮生长因子受体在胃癌组织的表达及意义

目的探讨胃癌组织中p53蛋白、ki-67抗原和表皮生长因子受体(EGFR)表达与TNM分期的关系。方法回顾性分析胃癌手术标本66例,采用免疫组织化学MaxVisionTM2/HRP法检测66例胃癌组织中p53、ki-67和EGFR的表达,分析其临床病理特征及与预后的关系。结果各分子标记物在胃癌组织中的阳性表达率为:p53蛋白53.03%(35/66),ki-67抗原62.12%(41/66),EGFR 42.42%(28/66)。P53蛋白表达与胃癌病灶直径、淋巴结转移密切相关(P<0.05),ki-67抗原阳性表达与胃癌分化密切相关(P<0.05),EGFR阳性表达与胃癌浸润深度、淋巴结转移密切相关(P<0.05)。p53、ki-67、EGFR三者联合检测与胃癌TNM分期密切相关(P<0.05)。结论 p53、ki-67、EGFR三者联合检测优于单独检测,与胃癌TNM分期相关。     

P53、nm23蛋白和血管内皮生长因子在鼻咽癌微血管生成中的作用

目的探讨p53、nm23基因和血管内皮生长因子(VEGF)在鼻咽癌微血管生成及转移中的作用。方法通过免疫组化SP法对64例鼻咽癌标本中p53、nm23蛋白、VEGF及CD34抗体进行了检测。结果鼻咽癌中P53、nm23蛋白及VEGF的阳性表达率分别为65.63%、53.12%和68.75%。p53蛋白表达和VEGF有一致性,呈正相关(P<0.01)。在有淋巴结转移的肿瘤中p53蛋白和VEGF阳性表达率及微血管密度(MVD)明显高于非转移组(P<0.05)。nm23基因和VEGF在鼻咽癌标本中无一致性和直接相关性,在nm23基因表达阴性和VEGF阳性标本中MVD较高,这种现象多见于有淋巴结转移的鼻咽癌中。结论p53基因通过调控VEGF的表达影响瘤内MVD,促使鼻咽癌发生转移;而nm23基因可能不是通过调控VEGF的表达,而是通过其它途径影响鼻咽癌转移。     

不同分子亚型的浸润性乳腺癌中nm23表达及与腋窝淋巴结转移的关系

目的探讨不同分子亚型浸润性乳腺癌中nm23的表达及其与腋窝淋巴结转移的关系。方法采用免疫组化法检测275例浸润性乳腺癌中nm23的表达水平。结果 nm23在激素受体阳性组、HER2受体阳性组、三阴性乳腺癌组中的表达率分别为84.3%、67.6%和54.5%(P0.05);nm23的阳性率在无腋窝淋巴结转移组中高于有腋窝淋巴结转移组(P0.05)。结论在乳腺癌的分子亚型中检测nm23的表达水平可以作为乳腺癌发生、发展的评价指标,更有助于指导其临床治疗和判断预后。     

Lipid messenger, diacylglycerol, and its regulator, diacylglycerol kinase, in cells, organs, and animals: history and perspective

Diacylglycerol kinase (DGK) metabolizes diacylglycerol (DG), a glycerolipid containing two acyl chains, to convert phosphatidic acid. DG is produced through phosphoinositide turnover within the membrane and is well known to act as a second messenger that modulates the activity of protein kinase C in the cellular signal transduction. Recent studies have revealed that DG also activates several proteins, including Ras guanine-nucleotide releasing protein and ion channels such as transient receptor potential proteins. Therefore, DGK is thought to participate in a number of signaling cascades by modulating levels of DG. Previous studies have disclosed that DGK is composed of a family of the isozymes, which differ in the structure, enzymological property, gene expression and localization, subcellular localization, and binding molecules. The present review focuses on the stories of phosphoinositide turnover and DG, including historical views, structural features, metabolism, and relevant cellular phenomena, together with the characteristics of DGK isozymes and the pathophysiological findings on animal studies using knockout mice and models for human diseases. Now it is being revealed that the structural and functional diversity and heterogeneity of and around DGK support the proper arrangement of the complex signal transduction machinery.     

NO and HNO donors,nitrones, and nitroxides: Past,present, and future

The biological effects attributed to nitric oxide (^?NO) and nitroxyl (HNO) have been extensively studied, propelling their array of putative clinical applications beyond cardiovascular disorders toward other age‐related diseases, like cancer and neurodegenerative diseases. In this context, the unique properties and reactivity of the N‐O bond enabled the development of several classes of compounds with potential clinical interest, among which ^?NO and HNO donors, nitrones, and nitroxides are of particular importance. Although primarily studied for their application as cardioprotective agents and/or molecular probes for radical detection, continuous efforts have unveiled a wide range of pharmacological activities and, ultimately, therapeutic applications. These efforts are of particular significance for diseases in which oxidative stress plays a key pathogenic role, as shown by a growing volume of in vitro and in vivo preclinical data. Although in its early stages, these efforts may provide valuable guidelines for the development of new and effective N‐O‐based drugs for age‐related disorders. In this report, we review recent advances in the chemistry of NO and HNO donors, nitrones, and nitroxides and discuss its pharmacological significance and potential therapeutic application.     

Heat, cold, noise, and vibration

Exposure to a cold environment induces a number of physiological alterations, the most serious being hypothermia. This state can occur in all individuals, but the very young and the elderly are more susceptible. Environmental and industrially generated high ambient temperature can place further stress on aged individuals and workers, resulting in a complex symptom picture. Morbidity and death may result from such exposures. Causative factors have been identified. Noise exposure induces hearing losses above those secondary to the aging process. Psychophysiological effects during noise exposure are considered to result from the sympathetic activity secondary to a general stress reaction. Vibration from the use of power tools results in Raynaud's phenomenon. However, modification of power tools has reduced the symptoms associated with vibration exposure. Termination of exposure to vibration appears eventually to reduce symptoms related to white-finger spasms. Interaction between these stressors has not been clarified because of the complex effects of each. The need for additional information about the response to these stressors is evident.