HSP90α和HSP90β在肝癌中共同上调表达

[目的]探讨热休克蛋白90α(HSP90α)和HSP90β在肝癌中的表达及意义.[方法]采用免疫组化法检测103例肝癌组织和79例非肝癌相关组织(正常肝组织,肝炎,肝硬化)中HSP90α和HSP90β的表达,并分析其与肝癌临床病理特征的关系.[结果]肝癌组织中,HSP90α和HSP90β的阳性表达率分别为82.52％和85.44％,均显著高于非癌组织(P＜0.05).HSP90α高表达与肝癌分化程度相关(P＜0.05),而与患者性别、病理类型、病理分期无关(P＞0.05).HSP90β高表达与肝癌分化程度和TNM分期相关(P＜0.05),而与患者性别、病理类型无关(P＞0.05).Spearman相关性分析显示,HSP90α和HSP90β在肝癌组织中协同表达(r=0.535,P＜0.001).[结论]HSP90α和HSP90β在肝癌组织中共同表达上调,可能可作为肝癌潜在的诊断和治疗靶点.     

FGA、HSP90α、SPP1联合对HBV相关性肝细胞癌的早期诊断价值

目的 探讨FGA、HSP90α、SPP1联合对HBV相关性肝细胞癌的早期诊断价值.方法 纳入早期HBV相关性肝细胞癌患者70例为肿瘤组、肝硬化患者70例为肝硬化组、健康体检者70例为对照组;检测肿瘤组、肝硬化组和对照组血清中FGA、HSP90α、SPP1的表达量;用受试者工作特征曲线(receiver operatin...     

HBV DNA阳性肝癌患者血清HBeAg检测与肝细胞癌复发转移的关系

目的:研究HBV DNA阳性肝癌(HCC)患者血清HBeAg检测与肝细胞癌复发转移的关系.方法: HBV DNA阳性HCC肝切除术患者60例,HBV DNA阴性HCC肝切除术患者60例.60例HBV DNA阳性HCC患者中依据肿瘤病灶局限、肉眼以及镜下均无肝内播散和门静脉浸润的低侵袭组,共28例;肿瘤组织伴有多发性肝内播散和(或)门静脉主肝癌栓者为高侵袭组,共32例.检测患者术前及术后1周血清HBV DNA水平,观察肝功能变化并检测血清HBeAg水平.结果:HBV DNA阳性组与HBV DNA阴性组比较,60例HBV DNA阳性HCC患者中HBeAg阳性患者为48例,阳性率为80%,60例HBV DNA阴性HCC患者中HBeAg阳性患者为12例,阳性率为20%,(P<0.05).不同侵袭组HBeAg表达比较: 32例高侵袭组中29例HBeAg检测阳性,阳性率为90.62% ,28例低侵袭组中19例HBeAg检测阳性, 阳性率为67.86%,(P<0.05).结论:早期肝癌患者血清HBV DNA和HBeAg可作为肝细胞癌复发转移监测指标.     

HSP90α和HSP90β蛋白在人骨肉瘤组织中的表达及临床意义

目的:探讨热休克蛋白HSP90α和HSP90β在骨肉瘤中的表达及意义。方法:采用免疫组化法检测90例骨肉瘤组织和21例癌旁组织中HSP90α和HSP90β的表达,并分析其与骨肉瘤临床病理特征的关系。结果:在骨肉瘤组织中,HSP90α和HSP90β的阳性表达率分别为57.78%和77.78%,均显著高于癌旁组织(P＜0.05)。HSP90α高表达与骨肉瘤Enneking外科分期相关(P＜0.05),而与患者性别、年龄、肿瘤位置无关(P＞0.05)。HSP90β高表达与骨肉瘤Enneking外科分期相关(P＜0.05),而与患者年龄、性别、肿瘤位置无关(P＞0.05)。Spearman相关性分析显示,HSP90α和HSP90β在骨肉瘤中协同表达(r=0.247,P＜0.05)。结论:HSP90α和HSP90β在骨肉瘤组织中共同表达上调,可能作为骨肿瘤潜在的诊断和治疗靶点。     

细胞表面热休克蛋白90与肿瘤转移

热休克蛋白90(Hsp90)调控其多种底物蛋白的稳定及功能,是抗肿瘤治疗的独特靶蛋白.Hsp90不仅位于细胞表面,甚至分泌至细胞外发挥一定功能,且与肿瘤高侵袭性及转移密切相关.     

不同转移潜能人肝癌细胞系的基因表达分析

目的：比较不同转移潜能人肝癌细胞系的基因表达谱,寻找与癌转移相关的基因表达改变。方法：采用基因芯片技术,比较遗传背景相同但转移力有明显差异的两个细胞系MHCC97－L和HCCLM3,分析其基因表达谱的差异。结果：在1626个候选基因中,筛选出25个差异表达基因。HCCLM3与MHCC97－L相比,表达上调的基因有8个,包括细胞增生基因E25、信号传导基因NKK6和免疫相关基因SP40,40等;下调的有17个,包括细胞周期调控基因Rb2、信号传导基因PKCβ2和错配修复基因hMSH2等。结论：肝癌转移是多基因作用的综合结果,筛选的基因对预测转移和抗转移干预措施可能有指导意义。     

细胞表面热休克蛋白90与肿瘤转移

热休克蛋白90(Hsp90)调控其多种底物蛋白的稳定及功能,是抗肿瘤治疗的独特靶蛋白.Hsp90不仅位于细胞表面,甚至分泌至细胞外发挥一定功能,且与肿瘤高侵袭性及转移密切相关.     

细胞表面热休克蛋白90与肿瘤转移

热休克蛋白90(Hsp90)调控其多种底物蛋白的稳定及功能,是抗肿瘤治疗的独特靶蛋白.Hsp90不仅位于细胞表面,甚至分泌至细胞外发挥一定功能,且与肿瘤高侵袭性及转移密切相关.     

热休克蛋白90α在肿瘤、食管癌中的研究

热休克蛋白90α（HSP90α）能够辅助蛋白折叠和维持细胞内多种信号传导蛋白的稳定,从而促进细胞存活和生长。在肿瘤细胞中,HSP90α能够使过度激活或突变的信号传导蛋白保持活性,加速肿瘤细胞的恶性转变。同时HSP90α还能被分泌到细胞外,可促进肿瘤的侵袭和转移。本文对HSP90α在肿瘤、食管癌中的表达、功能和分子作用机制作一综述。     

热休克蛋白90在食管鳞癌中的表达及临床意义

食管鳞状细胞癌(Esophagus squamous cell carcinoma,ESCC)是我国食管癌的主要病理分型,它起病隐匿、转移速度快,且给予治疗时产生耐药的速度快,导致预后不理想。热休克蛋白90(Heat shock protein 90,HSP90)调控的众多下游蛋白参与细胞的增殖等过程,所以在恶性肿瘤的发生发展中常扮演重要角色。越来越多的研究证实HSP90在多种恶性肿瘤中高表达并可影响肿瘤耐药性。近年来,对HSP90在ESCC中相关作用的探索也收获了许多值得关注的成果,本文将对HSP90在ESCC中的表达及临床意义做一综述。     

Targeting the molecular chaperone heat shock protein 90 (HSP90): Lessons learned and future directions

Due to the critical role of heat shock protein 90 (HSP90) in regulating the stability, activity and intracellular sorting of its client proteins involved in multiple oncogenic processes, HSP90 inhibitors are promising therapeutic agents for cancer treatment. In cancer cells, HSP90 client proteins play a major role in oncogenic signal transduction (i.e., mutant epidermal growth factor receptor), angiogenesis (i.e., vascular endothelial growth factor), anti-apoptosis (i.e., AKT), and metastasis (i.e., matrix metalloproteinase 2 and CD91), processes central to maintaining the cancer phenotype. Thus, HSP90 has emerged as a viable target for antitumor drug development, and several HSP90 inhibitors have transitioned to clinical trials. HSP90 inhibitors include geldanamycin and its derivatives (i.e., tanespimycin, alvespimycin, IPI-504), synthetic and small molecule inhibitors (i.e., AUY922, AT13387, STA9090, MPC3100), other inhibitors of HSP90 and its isoforms (i.e., shepherdin and 5′-N-ethylcarboxamideadenosine). With more than 200 “client” proteins, many of them meta-stable and oncogenic, HSP90 inhibition can affect an array of tumors. Here we review the molecular structure of HSP90, structural features of HSP90 inhibition, pharmacodynamic effects and tumor responses in clinical trials of HSP90 inhibitors. We also discuss lessons learned from completed clinical trials of HSP90 inhibitors, and future directions for these promising therapeutic agents.     

肝细胞肝癌血清AFP值与HBV感染的关系

目的:探索肝细胞肝癌患者血清AFP值与HBV感染模式的关系.方法:回顾性分析2009年1月到2011年6月于我院就诊并手术的所有肝脏恶性肿瘤患者的临床资料.结果:共有217例肝脏恶性肿瘤患者纳入研究:肝细胞肝癌(HCC)组176例,非HCC组41例.HCC组中HBV感染模式前三位的分别是HBsAg,HBeAb和HBcAb阳性(小三阳)(30.7％),HBsAg和HBcAb阳性(25.6％)及HBsAg,HBeAg和HBcAb阳性(大三阳)(20.5％).HCC组血清AFP值高于非HCC组血清AFP值(P ＜0.001),但HCC组内HBV感染组与非HBV感染组之间血清AFP水平无统计学差异(P =0.147),三种主要HBV感染模式之间血清AFP值也无统计学差异(P=0.578).同样的,无论在AFP阴性组(＜20ng/ml)还是AFP阳性组(≥20ng/ml),三种主要的HBV感染模式之间的血清AFP值均无统计学差异.结论:HCC的血清AFP值明显高于其他类型的肝脏恶性肿瘤血清AFP值,但HCC组内HBV的各种感染模式之间AFP值水平无差异.     

Radioembolization with Yttrium-90 microspheres for patients with unresectable hepatocellular carcinoma

Background

Hepatocellular carcinoma (HCC) is aggressive primary malignancy of the liver that most commonly presents late in the disease course. As a result, the majority of patients are not candidates for curative therapies. Locoregional therapies including Yttrium-90 (Y-90) radioembolization play an important role in management of the vast majority of patients with HCC.

Methods

Patients with unnresectable HCC (n=17) treated with Y-90 radioembolization from 2005 to 2014 were evaluated retrospectively. Data was abstracted from medical records including patient charts, laboratory data, and imaging. Toxicities were recorded using Common Terminology Criteria 3.0. Response was recorded according to modified RECIST (mRECIST) criteria.

Results

Seventeen patients received 33 treatments with Y-90 radioembolization. A majority (65%) received TheraSphere with a minority (35%) receiving SIR-Spheres. The median treatment activity delivered was 1.725 gBq (range, 1.4-2.5 gBq). The median treatment dose delivered was 100 Gy (range, 90-120 Gy). The median lung shunt fraction was 2.02% (range, 1.5-4.1%). The most common clinical toxicity among all patients was nausea and vomiting (59%), primarily grade 1 and 2. Other post-treatment findings included abdominal pain (29%), fatigue (53%), and weight loss (18%). One patient developed a grade 5 gastric ulcer after the treatment. A clinical benefit, defined as patients achieving complete response (CR), partial response (PR) or stable disease (SD), was seen in 48% of patients. PR was seen in 24% of cases; progressive disease (PD) was noted in 35%. Patients survived for a median of 8.4 months (range, 1.3 to 21.1 months) after the first radioembolization treatment. Median survival after Y-90 treatment was 8.4 months among patients treated TheraSphere as compared with 7.8 months in patients treated with SIR-Spheres. The mean overall survival from the time of diagnosis was 11.7 months (range, 3.4 to 43.2 months).

Conclusions

For patients with unresectable HCC, Y-90 radioembolization is a safe and well-tolerated procedure. Our experience suggests that a significant percentage of patients achieve clinical benefit including many with PR. Survival after treatment from this single-center, transplant center is in line with prior reports. Prospective, randomized data is required to compare radioembolization with other therapies including chemoembolization and systemic therapy with sorafenib.     

人胰腺癌高肝转移细胞株的建立及其意义

背景与目的：胰腺癌肝转移是胰腺癌晚期常见的症状，也是主要的致死原因。肿瘤转移是一个相当复杂的过程，建立胰腺癌肝转移模型是研究胰腺癌肝转移机理关键的一步。本研究通过连续人胰腺癌SW1990细胞脾脏移植法筛选出高肝转移胰腺癌细胞株，并对其转移相关特性进行分析。方法：人胰腺癌SW1990细胞脾内注射出现肝转移病灶后，将肝转移病灶肿瘤细胞体外原代培养扩增，再脾内注射出现肝转移病灶，此过程重复4次筛选到SW1990H4；然后比较SW1990H4和SW1990细胞株的核型、细胞体外增殖、细胞周期、体外侵袭、体内成瘤性、转移性和部分转移相关基因MMP-2、MMP-9、VEGF、bFGF和E—cadherin mRNA表达水平的差异。结果：SW1990H4和SW1990细胞株的核型及周期差异无显著性（P〉0．05）；SW1990H4体外细胞增殖速度、体外侵袭能力、移植瘤增长速度和肝转移率均显著高于SW1990细胞株（P〈0．05），SW1990H4细胞MMP-2、VEGF、bFGF和E—cadherin mRNA表达水平均高于SW1990，只有MMP-9 mRNA表达水平低于SW1990。结论：SW1990H4是人胰腺癌高肝转移细胞株，可应用于胰腺癌肝转移机制研究和抗肝转移药物的筛选。     

GRP94在HBV感染的人肝细胞肝癌中的表达及意义

目的:探讨葡萄糖调节蛋白(glucose-regulated protein 94,GRP94)在乙型肝炎病毒(hepatitis B virus,HBV)感染的人肝细胞肝癌(human hepatocellular carcinomas,HCC)中的表达及其意义。方法:酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)和实时荧光定量PCR（real-time fluorescence quantitative polymerase chain reaction,RTQF-PCR）方法来检测HCC患者血清。采用免疫组织化学(immunohistochemistry,IHC)方法、蛋白质印迹(Western blot)方法及半定量逆转录聚合酶链反应(reverse transcrition-polymerase chain reaction,RT-PCR),来探讨GRP94在HBV病毒感染的HCC和癌旁组织中的表达。结果:GRP94在癌旁组织中低表达,而在HCC中高表达,两者在Western blot、IHC及RT-PCR中的表达,其差异有统计学意义。同时HCC中GRP94的表达强度与肝癌患者肿瘤TNM分期(P=0.02)、肿瘤大小(P=0.01)、肿瘤结节的数目(P=0.02)、HBV-DNA的拷贝数值(P＜0.01)和血清甲胎蛋白（alpha-fetal protein,AFP）水平(P=0.02)相关,但与患者的性别、年龄差异无关。结论:GRP94与HCC临床病理特征存在一定的相关性,对HCC治疗、预后判定具有一定指导意义。     

Involvement of human heat shock protein 90 alpha in nicotine-induced apoptosis

There have been conflicting reports of the apoptotic effects of nicotine on human cells and those studies reporting nicotine-induced apoptosis have not unequivocally clarified the molecular mechanisms underlying the effect. However, we found here that human RSa cells, established from embryonic fibroblastic cells doubly infected with Rous sarcoma virus and Simian virus 40, underwent apoptosis when cultured with medium containing 0.06-0.6 microM nicotine. The apoptosis was assessed by cellular DNA fragmentation and caspase-3 protease activation. Viability of RSa cells was reduced by nicotine treatment, as analyzed by MTT assay and the reduction was lessened by combination treatment with a caspase-3 inhibitor, acetyl-L-aspartyl-L-glutamyl-L-valyl-L-aspart-1-al (Ac-DEVD-CHO). Levels of expression of heat shock protein 90 alpha (Hsp90 alpha) were found to be increased 20 min after the nicotine treatment, as analyzed by polymerase chain reaction-based mRNA differential display after Northern blotting analysis of mRNA amounts. Cellular contents of Hsp90 alpha were furthermore increased in the nicotine-treated RSa cells, as quantitated by Western immunoblot analysis. By contrast, in RSa cells treated with nicotine in combination with geldanamycin (GA), an inhibitor of Hsp90 alpha function, DNA fragmentation was not detected and caspase-3 protease activity levels were the same as those of mock-treated cells. Nicotine-induced caspase-3 activation and Hsp90 alpha expression, as well as suppression of the induction by GA, were also observed in a xeroderma pigmentosum patient-derived cell line, XP2OS cells. Thus, it was suggested that nicotine induces apoptosis, possibly via Hsp90 alpha expression, in human cells tested.     

人食管鳞癌组织中热休克蛋白72和糖蛋白96的表达及其意义

目的：探讨热休克蛋白72（HSP72）和糖蛋白96（gp96）在人食管鳞癌组织中的表达及其意义。方法：利用EnVision免疫组织化学和图像分析方法检测人食管鳞癌组织及其癌旁组织中HSP72和gp96的表达与临床病理的关系。结果：90例食管鳞癌中85例（94．4％）HSP72呈现阳性，主要定位于细胞核，而gp96主要表达于胞浆，其阳性率为80．0％（72／90）。HSP72和gp96在食管鳞癌和癌旁组织中的表达存在明显的差异（P〈0．01）。与癌旁组织相比，HSP72的表达与肿瘤的分化程度具有一定的相关性。结论：食管鳞癌组织存在HSP72和sp96的高表达。HSP72和gp96在人食管鳞癌细胞中的表达对于研究食管鳞癌的进展和预后具有一定的意义。