66 例晚期黑色素瘤患者组织中磷酸化成视网膜细胞瘤蛋白表达水平分析及其临床意义评价

[摘要] 目的：分析晚期黑色素瘤组织中磷酸化成视网膜细胞瘤蛋白（phosphorylated retinoblastoma,p-Rb）的表达情况,并探讨其与临床病理特征及预后之间的相关性。方法：收集2011 至2014 年在北京大学肿瘤医院肾癌黑色素瘤科住院治疗并符合纳入和排除标准的66 例晚期黑色素瘤患者的临床资料及其石蜡包埋组织切片,采用免疫组化方法检测患者原发灶肿瘤组织中p-Rb 的表达情况,结合患者临床病理特征、总生存期等临床数据进行相关性分析。结果：晚期黑色素瘤组织中p-Rb 的阳性表达率为57.6%(38/66)。非肢端的皮肤型、肢端型及黏膜型的p-Rb阳性率分别为73.7%（14/19）、63.0%（17/27）和35.0%（7/20）,差异有统计学意义（P=0.039）。p-Rb 在不同基因突变亚组中的阳性率亦不同,BRAF突变组为83.3%（5/6）,C-KIT 突变组为100.0%（2/2）,N-RAS突变组为100.0%(9/9),PDGFRA突变组为50.0%（1/2）,2 个基因突变组为50.0%（1/2）,基因野生型为44.4%（20/45）,差异有统计学意义（P=0.004）。p-Rb表达水平与年龄、性别、分期、溃疡、血清LDH水平无相关性（P>0.05)。p-Rb 阳性患者的中位总生存期（OS）较阴性患者略短（30.0 vs 39.2 个月）,但差异无统计学意义（P=0.555）。结论：超过半数的晚期黑色素瘤组织中有p-Rb 的阳性表达,非肢端的皮肤型中p-Rb阳性率高于肢端型、黏膜型,且携带c-KIT 和N-RAS突变的患者黑色素瘤组织中p-Rb阳性率较高。     

人参皂苷Rb3对中国仓鼠肺细胞染色体畸变作用

目的研究人参皂苷Rb3对中国仓鼠肺细胞(CHL)染色体畸变作用。方法测定人参皂苷Rb3对CHL细胞的半数抑制浓度(IC50),根据IC50设立不同剂量组,进行染色体畸变试验,分别观察人参皂苷Rb3接触CHL细胞6 h、24 h及加S9后6 h染色体的畸变情况,根据标准进行结果判定。结果染毒6 h、24 h及加S9后染毒6 h染色体畸变为阴性。结论人参皂苷Rb3不能引起CHL细胞染色体产生畸变作用。     

Rb与cyclinD1在骨肉瘤中的表达及其意义

目的 研究Ｒｂ与ｃｙｃｌｉｎＤ１蛋白在骨肉瘤中的表达及其意义。方法 采用免疫组织化学方法对４７例骨肉瘤及１８例良性骨肿瘤组织标本进行Ｒｂ、ｃｙｃｌｉｎＤ１蛋白表达检测。结果 ｃｙｃｌｉｎＤ１在骨肉瘤标本中的表达高于良性骨肿瘤组织中的表达（Ｐ〈０．０５）,其差异有显著性。Ｒｂ蛋白在骨肉瘤标本中的表达低于良性骨肿瘤标本中的表达（Ｐ〈０．０５）,其差异有显著性。Ｒｂ蛋白表达在骨肉瘤临床分期ⅡＡ与Ⅲ期之间     

Necdin蛋白与神经元的生长分化

在神经系统 ,Necdin只在成熟神经元的细胞核中表达 ,可能与成熟神经元分裂静止状态的保持有关。近年的研究表明 ,Necdin是一种生长抑制蛋白 ,能与多种因子如SV4 0大T抗原 ,腺病毒E1A ,转录因子E2F1以及肿瘤抑制蛋白p5 3等结合 ,在功能上类似于成视网膜瘤蛋白Rb。necdin基因缺陷时 ,会引起脑内 ,特别是下丘脑神经元分化障碍。人类necdin基因位于PWS综合征的基因缺失区 ,可能与PWS的一些症状有关。本文从Necdin蛋白的基本概况 ,生物功能以及Necdin与疾病三个方面进行了综述     

三七叶与茎HPLC的比较分析及Rb3含量的测定

目的：比较三七叶和三七茎的皂苷成分,为叶苷相关产品的质量提供技术保障。方法采用HPLC,对三七叶和三七茎的皂苷成分进行比较,其中主要以人参皂苷Rb3、Rb1的含量为考察指标。结果三七叶中主要成分为Rb3,其中三个产地的三七叶中Rb3平均含量为1.025%.三七茎秆中以Rb1为主,Rb3微量。结论三七叶和三七茎中主要皂苷成分有显著的差异,为保证叶苷产品的质量稳定,应重视生产原料的选择,控制三七叶和茎的比例。     

人参皂苷Rg3逆转人食管癌耐顺铂细胞Eca109／DDP的作用机制

目的研究人参皂苷Rg3（ginsenosideRg3,Rg3）对人食管癌耐顺铂细胞Eca109／DDP的耐药性的逆转作用及可能机制,为提高食管癌化疗疗效提供新方法。方法应用MTr法及流式细胞检测Rg3和（或）顺铂（cisplatin,DDP）对细胞Eca109／DDP增殖的影响;免疫组织化学法及Westernblot印迹法检测细胞P糖蛋白（p-glycoprotein,P—gP）的变化。结果Rg3显著降低了DDP对Eca109／DDP细胞的Ic50,逆转倍数为2．0倍,细胞周期分析显示,Eca109／DDP细胞被阻滞在G,期的数量显著增加;而Rg3和DDP联合作用肿瘤48h后P-gP表达水平显著下降。结论低细胞毒剂量Rg3可部分逆转Eca109／DDP对食管癌的耐药性,下调的P-gP表达可能是逆转作用的机制之一。     

Hepatoprotective effect of ginsenoside Rb1 and compound K on tert-butyl hydroperoxide-induced liver injury.

BACKGROUND/AIM: The main component of Panax ginseng, which have been reported by many researchers, are ginsenoside Rb1, Rb2 and Rc. Orally administered ginsenosides are metabolized to 20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol (compound K) by intestinal bacteria and absorbed to blood. To understand its hepatoprotective effect and its mechanism, the effects of ginsenoside Rb1 and its metabolite compound K on chemically injured HepG2 cells and mice were investigated. METHODS: Ginsenoside Rb1 and compound K were isolated from ginseng. Hepatotoxicity of HepG2 cells and mice was induced by tert-butyl hydroperoxide (t-BHP). Cytotoxicity for HepG2 cells and serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) for mice as markers of hepatoprotective activity were measured. RESULTS: Compound K protected HepG2 cell cytotoxicity induced by t-BHP. However, ginsenoside Rb1 did not inhibit cytotoxicity. Nevertheless, both ginsenoside Rb1 and compound K significantly inhibited the increment of ALT and AST induced by t-BHP in mice, when it was orally administered. However, intraperitoneally administered ginsenoside Rb1 did not inhibit the increment of plasma ALT and AST induced by t-BHP in mice. These compounds did not exhibit antioxidant activity. However, compound K showed the potent membrane stabilizing activity more than ginsenoside Rb1. CONCLUSION: Compound K, which was produced from ginsenosides of Panax ginseng in intestine, could protect liver injury.     

人参皂甙Rg3对子宫内膜异位症模型大鼠疗效观察

目的探讨人参皂甙Rg3治疗子宫内膜异位症模型大鼠后对血清CA125水平的影响。方法参照Jones方法建立Wistar大鼠EMs动物模型,3周后将建模成功的大鼠随机分为三组,空白对照组,人参皂甙Rg3组,孕三烯酮组,每组各20只,观察不同时期异位囊肿体积的变化,采用ELISA法检测血清中CA125变化。结果用药后人参皂甙Rg3组、孕三烯酮组与空白对照组有效率比较差异显著（P〈0.05）;人参皂甙Rg3组与孕三烯酮组有效率比较差异显著（P〈0.05）;人参皂甙Rg3组、孕三烯酮组与空白对照组血清CA125水平比较差异有统计学意义（P〈0.05）;停药8周,人参皂甙Rg3组与孕三烯酮组比较差异有统计学意义（P〈0.05）。结论人参皂甙Rg3对子宫内膜异位症有较好治疗效果,治疗后复发率低,值得在临床上推广应用。     

Targeting Rb inactivation in cancers by synthetic lethality

The retinoblastoma protein, pRb, is a key regulator of cell proliferation, differentiation, apoptosis, as well as checkpoint and stress responses. The function of Rb is often inactivated in many types of cancers, a feature that can potentially be used to target this specific subset of cancers. However little is known about how the loss of Rb function can be exploited in cancer therapies. In this review, we overview the functions of Rb, and discuss a genetic screen that led to the finding that inactivation of TSC2 and Rb induces synergistic cell death in both Drosophila developing tissues and human cancer cells. The mechanisms for synergistic cell death involve the accumulation of cellular stress, suggesting that inactivation of TSC2 and chemotherapeutic agents that result in induction of cellular stress can potentially be combined to treat cancers harboring inactivated Rb.     

人参皂苷Rg3含量的变化

目的:建立经真菌转化前后三七中人参皂苷Rg3的含量测定方法。方法:采用HPLC法,色谱柱为Phenomex C18(250mm×4.6mm,5μm),流动相为乙腈-水,梯度洗脱;柱温30℃,检测波长为203nm,流速1.0mL/min,进样量为20μL。结果:人参皂苷Rg3的回归方程:Y=35672013X-2413,r=0.99992,在0.0019～0.2488 mg/mL范围内有良好的线性关系,平均回收率为99.56%,RSD=1.48%(n=8)。结论:该方法简便、快捷、准确、重复性好,可用于三七发酵产物中人参皂苷Rg3的含量测定。