Hepatitis B viral load affects prognosis of hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is a complex disease that is dually challenging to treat due to underlying chronic liver disease in addition to the cancer itself.The prognosis of patients with HCC is determined by intrahepatic tumor status and reserved hepatic function.Hepatitis B virus(HBV)is an established major risk factor of HCC development,and HBV viral load is being increasingly recognized as a prognostic factor in the presence of established HCC.High HBV viral load may affect the prognosis of HBV-related HCC patients in several ways.First,it is associated with more frequent recurrence of HBV-related HCC after treatment.Second,it is associated with more occurrence and severity of potentially life-threatening HBV reactivation.Last,it is associated with more worsened liver function,which limits the therapeutic options for HBV-related HCC.HBV,directly or indirectly,can induce hepatocarcinogenesis.In patients with a high HBV DNA level and subsequent active hepatitis,adhesion molecules expressed on the sinusoidal cells are up-regulated and may increase intrahepatic metastasis.HCC progression after treatment can lead to a poor prognosis by reducing number of normal functioning hepatocytes.Thus,high HBV viral load can affect the prognosis of patientswith HCC by frequent recurrence after treatment for HCC and deterioration of hepatic function associated with HCC progression.Recent meta-analysis showed that antiviral treatment reduces HCC recurrence and liver-related mortality after curative therapy of HCC.Given the strong relationship between high HBV DNA load and poor survival outcome of HCC patients due to cancer progression,it is expected that long-term antiviral therapy results in the sustained HBV suppression,control of inflammation,reduction in HCC progression,and eventually in improved overall survival.     

Significant correlation between expression level of HSP gp96 and progression of hepatitis B virus induced diseases

AIM:Gp96,also known as Grp94,is a member of heatshock protein (HSP) family and binds repertoires of peptidesthereof eliciting peptide-specific T cell immune responses.It predominantly locates inside the endoplasmic reticulum(ER) with some cell surface expression in certain cancerouscells.Previous studies have shown that gp96 expressionlevel was up-regulated in tumor cells,including hepatocellularcarcinoma (HCC).However,relationship between theextent of gp96 expression and disease progression especiallyHBV-induced chronic infection,cirrhosis and hepatocellularcarcinoma,has not been addressed before.As primary HCCcan be induced and progressed from chronic hepatitis Bvirus (HBV) infection and HBV-induced cirrhosis,wedesigned an immunohistochemical experiment to test thecorrelation between gp96 expression level and HBV-induceddisease progression,from chronic HBV infection,cirrhosisto HCC.METHODS:We chose liver samples from different patientsof hepatitis B virus induced diseases,including chronichepatitis B (77 patients),cirrhosis (27 patients) and primaryHCC (30 patients),to test the expression level of gp96 indifferent affected groups.Formalin-fixed,and paraffin-embedded liver tissues taken from these patients wereimmuno-stained by using an anti-gp96 monoclonal antibodyfor the expression level of gp96 protein in the sections.Inaddition,Western blotting of whole cell lysates derived fromestablished human embryonic liver cell lines and severalhuman HCC cell lines (Huh7,HepG2,SSMC-7721) wascompared with the expression of gp96.RESULTS:We found that the extent of elevated gp96expression was significantly correlated with the diseaseprogression,and was the highest in HCC patients,lowestin chronic HBV infection and was that of the cirrhosis inthe middle.CONCLUSION:Increased expression of gp96 might be usedas a diagnostic or prognostic bio-marker for the HBV infectionand HBV-induced diseases.     

Decaprenyl diphosphate synthase subunit 2 as a prognosis factor in hepatocellular carcinoma

AIM:To investigate the involvement of decaprenyl diphosphate synthase subunit 2(PDSS2) in development and progression of human hepatocellular carcinoma(HCC).METHODS:PDSS2 protein expression was examined in well-and poorly differentiated HCC tumor samples.The levels of PDSS2 expression were compared with clinical features and prognosis of HCC patients.The effects of PDSS2 on cell proliferation,cell cycle,apoptosis,cell migration,and invasion in HCC Hep G2 cells were also investigated.RESULTS:PDSS2 was downregulated in poorly differentiated cancer samples compared with welldifferentiated tumor samples,and the expression level was markedly lower in HCC tissues than in histologically normal tissue adjacent to the cancer.Reduced protein expression was negatively associated with the status of HCC progression.In addition,overexpression of PDSS2dramatically suppressed cell proliferation and colony formation,and induced apoptosis in Hep G2 cells by inducing G1-phase cell-cycle arrest.The migration and invasion capabilities of Hep G2 cells were significantly decreased following PDSS2 overexpression.CONCLUSION:Decreased PDSS2 expression is an unfavorable prognostic factor for HCC,and PDSS2 has potent anticancer activity in HCC tissues and Hep G2cells.     

Clinical significance of nerve growth factor and tropomyosin-receptor-kinase signaling pathway in intrahepatic cholangiocarcinoma

AIM:To investigate the correlation between nerve growth factor-tropomyosin-receptor-kinase(NGF-TrkA)signaling pathway and prognosis in intrahepatic cholangiocarcinoma(IHCC).METHODS:NGF and TrkA expression in 83 samples of IHCC was assessed by immunohistochemistry.Correlations between NGF-TrkA expression and clinicopathological features were analyzed byχ2 test.Moreover,we evaluated the association between NGF-TrkA and overall survival by univariate and multivariate analysis.With experiments in vitro,we investigated the crucial role of NGF-TrkA on proliferation and invasion of IHCC cells with recombinant NGF-βstimulation.RESULTS:We found that NGF and TrkA expression was significantly related with differentiation(P=0.024)and intraneural invasion(P=0.003),respectively.Additionally,double higher expression of NGF and TrkA was identified as an independent prognostic factor in IHCC(P=0.003).Moreover,we demonstrated that NGF-TrkA signaling pathway can promote IHCC proliferation and invasion.CONCLUSION:NGF-TrkA double higher expression is an independent prognostic factor in IHCC.NGF-TrkA pathway can promote IHCC progression,indicating that NGF-TrkA may become a potential drug target.     

Expression of HSP90 and HIF-1α in human colorectal cancer tissue and its significance

Objective:To investigate the expression of HSP90 and HIF-1αin human colorectal cancer tissue,the influence of HSP90 and HIF-1αon human colorectal cancer biological behavior and their related factors.Methods:The expression of HSP90 and HIF-1 a protein in human colorectal cancer as well as normal tissue were detected by imnmnohistochemical method.Results:The positive expression rates of HSP90 and HIF-1αprotein in normal human colorectal tissue as well as colorectal cancer tissue were 30%vs.63.0%,15.0%vs.71.7%,respectively.There were significant difference(P=0.035 and P=0.005 respectively).The expression of HSP90 was significantly correlated with the differentiation,Dukes stages and lymph node metastasis(P0.05),while the expression of HIF-1 a was significantly correlated with the Dukes stages and lymph node metastasis(P0.05).Association analysis showed that the expression of HSF90 protein was significantly correlated with that of HIF-1αprotein(P0.01).Conclusions:The expression of HSP90 and HIF—1αprotein may be related to the development,metastasis and invasion of human colorectal cancer,and their synergistic effects may participate in the development of the colorectal carcinoma.     

hMex-3A is associated with poor prognosis and contributes to the progression of hepatocellular carcinoma

Background: HMex-3A, an RNA-binding protein, was found to be associated with tumorigenesis. However, the roles of h Mex-3A in hepatocellular carcinoma(HCC) progression remained unclear. Methods: The different expression of h Mex-3A between HCC tissues and non-tumor tissues was evaluated using The Cancer Genome Atlas database. Thereafter, the h Mex-3A expression was evaluated in HCC tissues using Western blotting and q RT-PCR. Immunohistochemistry was performed to investigate the association between h Mex-3 A level and clinicopathological features including prognosis in HCC patients. In addition, we used si-h Mex-3A to knockdown h Mex-3A in HCC cells to test Cell Counting Kit-8, colony formation, cell migration and invasion. Results: The h Mex-3A expression was significantly elevated in HCC tissues. Analysis of the clinicopathological parameters suggested that h Mex-3A expression was significantly associated with pathological grade( P = 0.019) and TNM stage( P = 0.001) in HCC. Moreover, univariate and multivariate Coxregression analyses revealed that high h Mex-3A expression(HR = 1.491, 95% CI: 1.107–2.007; P = 0.009) was an independent risk factor for overall survival in HCC patients. Finally, we confirmed that si-h Mex-3A could significantly inhibit HCC cell proliferation, migration, and invasion in vitro. Conclusions: HMex-3A may contribute to the progression of HCC and might be used as a novel therapeutic target and prognostic marker in HCC.     

Relationship between cell adhesion molecules expression and the biological behavior of gastric carcinoma

AIM： To evaluate the relationship between the expression of cell adhesion molecules （CAMs） and the biological behavior of gastric carcinoma. METHODS： Expression of syndecan-1, E-cadherin and integrin β3 were evaluated by immunohistochemical study in a total of 118 gastric carcinomas and 20 nontumor gastric mucosas. RESULTS： The expressions of syndecan-1 and E-cadherin were significantly lower in gastric carcinoma compared to non-tumor gastric mucosa, and the low expression rates were positively correlated to the tumor invasion depth, vessel invasion, lymph node metastasis and distant metastasis （P 〈 0.01 in all cases）. However, the expression of integrin β3 was significantly higher in gastric carcinoma compared to non-tumor gastric mucosa, and the high expression rates were positively correlated to the tumor invasion depth, vessel invasion, lymph node metastasis and distant metastasis （P 〈 0.01 in all cases）. In addition, the three protein expressions were correlated to the tumor growth pattern （P 〈 0.01, P 〈 0.01, and P 〈 0.05 respectively）, but not correlated to tumor differentiation （P 〉 0.05, P 〉 0.05 and P 〉 0.05 respectively）. Positive correlation was observed between the expressions of syndecan-1 and E-cadherin, but they which were negatively correlated to the expression of integrin β3 （P 〈 0.01 in all cases）. Univariate analysis demonstrated that the mean survival time and 5-year survival rate were lower in the cases with low expressions of syndecan-1 and E-cadherin and high expression of integrin β3 （P 〈 0.01, in all cases）. COX multivariate analysis showed that the expression level of syndecan-1 could be an independent prognostic index of gastric carcinoma （P 〈 0.01）, whereas E-cadherin and integrin β3 could not be independent indexes （P 〉 0.05, P 〉 0.05 respectively）.CONCLUSION： The low expression of syndecan-1 and E-cadherin and the high expression of integrin β3 are significantly correlated with the invasion and metastasis o     

Expression and significance of heat shock protein 70 and glucose-regulated protein 94 in human esophageal carcinoma

AIM: To investigate the expression and significance of heat shock protein 70 (HSP70) and glucose-regulated protein 94 (grp94) in human esophageai carcinoma and adjacent normal tissues. METHODS: The expression of HSP70 and grp94 in 78 human esophageai cancer and adjacent normal tissues was studied by immunohistochemistry and pathology photograph analysis. RESULTS: Both esophageai cancer and adjacent normal tissues could express HSP70 and grp94. Of the 78 cases of esophageai carcinoma, 95.0%(72/78) showed positive HSP70, mainly stained in nuclei, while grp94 was mainly stained in cell plasma, and the positive rate was 71.8% (56/78).There was a significant difference in the expression of HSP70 and grp94 between esophageai cancer and adjacent normal tissues (P<0.01). Compared with adjacent normal tissues, there was a significant difference between differential types and HSP70 expression (P<0.01). CONCLUSION: HSP70 and grp94 express differently in cell plasma and nuclei. The expression intensity of HSP70 is related to the differentiation of esophageai carcinoma.     

Abnormal expression of HSP gp96 associated with HBV replication in human hepatocellular carcinoma

BACKGROUND: Heat shock protein (HSP) gp96 is a member of the HSP90 family and presumably overexpresses as a result of stimulation by mutated or abnormal proteins. Its abnormal expression correlates with carcinogenesis, progression and prognosis of hepatocellular carcinoma (HCC). In this study, we investigated the pathological characteristics of liver gp96 expression and its relationship with hepatitis B virus (HBV) replication in HCC patients. METHODS: Tumor specimens were prospectively collected from 30 HCC patients undergoing liver resection. Total RNAs were extracted from HCC or their noncancerous tissues. The distribution of gp96 expression in hepatocytes was investigated by streptavidin peroxidase (S-P) immunohistochemistry and tissue HBV-DNA was detected by the in situ molecular hybridization technique. The association of gp96 expression with HBV replication, and the histopathological characteristics of HCC were analyzed. RESULTS: The gp96 was strongly expressed in HCC (73.3%, 22 of 30) and weakly (46.7%, 14 of 30) in non-cancerous tissues. The gp96 expression in HCC tissues was correlated with degree of tumor differentiation and tumor size, but not with tumor number (P>0.05). Immunohistochemical analysis showed that 17 of 19 HCC patients with HBVDNA -positive were strongly expressed for gp96, whereas only 5 of 11 patients with HBV-DNA-negative were positive for gp96. A significant difference was found between the two groups (89.5% vs. 45.5%, P<0.05). CONCLUSIONS: The abnormal expressions of HSP gp96 in HCC tissues are associated with HBV replication. This finding indicates that HBV infection plays an important role in the development of HCC.     

Prognostic signif icance of HIF-2α/EPAS1 expression in hepatocellular carcinoma

AIM: To evaluate the prognostic signif icance of HIF- 2α/EPAS1 expression in hepatocellular carcinoma (HCC). METHODS: Surgical specimens from 315 patients with HCC as well as 196 adjacent noncancerous lesions and 22 cases of normal liver tissue were investigated by immunohistochemistry (IHC) for HIF-2α/EPAS1 using a standard detection system. Correlations with clinicopathological factors, VEGF, microvessel density (MVD), and prognosis were analyzed. RESULTS: Immunoreactivity of HIF-2α/EPAS1 was positive in 69.5% of HCC, 55.6% of adjacent noncancerous tissue, and 0% of normal liver tissue. And it was significantly correlated with tumor grade, venous invasion, intrahepatic metastasis, necrosis, and capsule infiltration. Correlation analysis of HIF-2α/EPAS1 with angiogenic factor VEGF (P < 0.001), and MVD (P = 0.016) was also noted. HIF-2α/EPAS1 protein was less frequently expressed in low MVD cases, whereas a high rate of expression was noted in cases with both medium and high MVD (P = 0.042). By Kaplan-Meier analysis, strong HIF-2α/EPAS1 staining (> 50% of tumor cells) in HCC correlated with a shortened survival in patients (Cox's regression, P < 0.001, r = 3.699). CONCLUSION: We conclude that HIF-2α/EPAS1 expression may play an important role in tumor progression and prognosis of HCC. Assessment of HIF-2α/EPAS1 expression in HCC may be used as a diagnostic tool and possibly a target in the treatment of HCC.     

Hyperthermia induces multiple pancreatic heat shock proteins and protects against subsequent arginine-induced acute pancreatitis in rats

Heat shock proteins (HSPs) which are induced by stress can provide protection against subsequent cellular damage. Whole body hyperthermia in rats leading to induction of HSP70 has been shown to protect against subsequent caerulein-induced acute pancreatitis. We studied the effect of hyperthermia on pancreatic HSP expression and found a significant increase in HSP70 (26.0-fold) and HPS27 (6.0-fold) but no change in HSP60, HSP90 or GRP78. Hyperthermia conferred significant protection against subsequent arginine-induced acute pancreatitis. More specifically, the degradation and disorganization of the actin cytoskeleton, an important early component of acute pancreatitis, was prevented. These results generalize previous work on caerulein-induced pancreatitis to another model of experimental pancreatitis, arginine-induced pancreatitis, and suggest that multiple HSPs may be involved in the cytoprotective effect in rat pancreas.     

Regional distribution of HSP 70 proteins after myocardial infarction

Hypoxia and altered hemodynamic status, both components of myocardial infarction, have been shown to be potent inducers of the 70 kD family of heat shock proteins (HSP70). We hypothesized that after infarction, the surviving myocardium would synthesize HSP70 proteins in a temporally and regionally distinct pattern. We believed that there would be a lack of an HSP70 response in the infarcted area (I), reflecting the loss of viable cells. We further postulated that tissues bordering infarctions (M) would have a compromised HSP70 response. Conversely, we proposed that HSP70 would be induced in septal tissues (S) of the infarcted heart, as a hypertrophic adaptation. A rat model of myocardial infarction was used to examine the changes in relative concentration and distribution of three major HSP70 family proteins; cytoplasmic HSP72, mitochondrial HSP75, and endoplasmic reticular GRP78 (glucose regulated protein) during 21 days of recovery. While all three HSP70 family proteins investigated were detected in all hearts from all groups at all time periods, experimental treatment (infarction) induced changes in relative protein concentrations that varied with time and sample site location. Relative concentrations of HSP72 and GRP78 were unchanged in the 24 h following infarction while relative HSP75 concentrations were halved in M tissues during the same time period. Between days 5 and 7, several changes were noted. M samples displayed nearly twice the relative concentrations of HSP75 and GRP78 after infarction, but showed no change in HSP72. S tissues showed two-fold or larger increases in all three HSP70 family proteins. I samples showed unanticipated increases in HSP75 and GRP78 during this time period. After 14 to 21 days of recovery, HSP70 family protein concentration levels in M, S, and I tissues from infarcted hearts had returned to levels similar to those seen in control animals. We conclude that the myocardium is unable to, or does not, mount an immediate HSP70 response after infarction but does recover such activity by 5–7 days after infarction.This study was supported in part by a grant from the American Heart Association-Kansas Affiliate (KS-94-GS-30)     

大鼠脑缺血后内质网伴侣蛋白GRP78和GRP94及胱冬酶12表达的改变

目的观察大鼠局灶性脑缺血时内质网分子伴侣葡萄糖调节蛋白（glucose-regulatedprotein GRP）78、GRP94及内质网凋亡因子胱冬酶（easpase）12的变化,探讨内质网分子伴侣及凋亡因子在脑缺血损伤中的作用.方法Wistar大鼠60只,雌雄各半,随机分为假手术组和缺血组,各为30只.采用线栓法制备大鼠局灶脑缺血模型.应用免疫组织化学及半定量逆转录-聚合酶链反应（RT-PCR）方法检测缺血6、12、24h大鼠纹状体GRP78、GRP94及caspase-12 mRNA表达变化.结果免疫组织化学和RT-PCR检测均发现缺血组GRP78、GRP94 mRNA表达低于假手术组（P＜0.05）;其mRNA及蛋白表达在缺血12 h达峰值,与6、24 h比较差异有显著性（P＜0.05）.缺血组缺血6h caspase-12表达升高,12 h达高峰,24h明显下降;假手术组未见caspase-12表达.结论大鼠纹状体缺血后可能通过GRP78、GRP94表达升高启动内质网自稳调节系统;严重的脑损伤GRP78、GRP94表达下降.内质网caspase-12凋亡通路的启动可能是脑缺血损伤的又一机制.     

GRP78的表达非小细胞性肺癌细胞A549对顺铂的敏感性

目的探讨下调GRP78的表达后是否增强非小细胞性肺癌细胞对顺铂的敏感性。方法通过蛋白印记的方法检测内质网应激后GRP78的表达变化;用流式细胞仪检测用siRNAGRP 78抑制GRP 78的表达上调后凋亡细胞的数目;用A549肿瘤细胞对裸鼠进行了皮下荷瘤,在体内检验GRP78的表达水平对顺铂耐药的影响;运用免疫组织化学的方法检测肺癌患者的肿瘤组织中GRP78的表达水平。结果内质网应激能上调GRP78的表达;抑制内质网应激诱导的GRP78的表达上调后,细胞对顺铂的敏感性增加;将GRP78基因表达干扰后,荷瘤组织的生长明显受到顺铂的抑制;20例肺癌患者的肿瘤组织与癌旁组织相比,存在GRP78的高表达。结论 GRP78的表达水平上调降低非小细胞性肺癌细胞对顺铂的敏感性,具体的参与调控的信号通路需要进一步的机制研究。     

Two mammalian heat shock proteins, HSP90 and HSP100, are actin-binding proteins.

Two high molecular weight heat shock proteins, HSP90 (Mr, 90,000) and HSP100 (Mr, 100,000), were separately purified from extracts of cultured cells of a mouse lymphoma cell line, L5178Y. Both of the HSPs exist in homodimeric form under physiological conditions. Their physicochemical properties are quite similar to each other. Each of the purified HSPs was shown to coprecipitate with rabbit skeletal muscle actin under actin-polymerizing conditions. Both HSP90 and HSP100 increased the low-shear viscosity of filamentous actin solutions in a dose-dependent manner, which suggests that these HSPs cross-link actin filaments. Although some molecular properties and the effects described above on actin solution of HSP90 and HSP100 resemble those of alpha-actinin, the HSPs were distinguished from alpha-actinin by various means, including visualization of molecular shapes by electron microscopy with the aid of the low-angle rotary shadowing technique. Immunofluorescence staining by specific antisera against HSP90 revealed that HSP90 was localized in ruffling membranes in addition to the cytoplasmic space.     

Significant correlation between expression level of HSP gp96 and progression of hepatitis B virus induced diseases

AIM: Gp96, also known as Grp94, is a member of heat shock protein (HSP) family and binds repertoires of peptides thereof eliciting peptide-specific T cell immune responses. It predominantly locates inside the endoplasmic reticulum (ER) with some cell surface expression in certain cancerous cells. Previous studies have shown that gp96 expression level was up-regulated in tumor cells, including hepatocellular carcinoma (HCC). However, relationship between the extent of gp96 expression and disease progression especially HBV-induced chronic infection, cirrhosis and hepatocellular carcinoma, has not been addressed before. As primary HCC can be induced and progressed from chronic hepatitis B virus (HBV) infection and HBV-induced cirrhosis, we designed an immunohistochemical experiment to test the correlation between gp96 expression level and HBV-induced disease progression, from chronic HBV infection, cirrhosis to HCC. METHODS: We chose liver samples from different patients of hepatitis B virus induced diseases, including chronic hepatitis B (77 patients), cirrhosis (27 patients) and primary HCC (30 patients), to test the expression level of gp96 in different affected groups. Formalin-fixed, and paraffin-embedded liver tissues taken from these patients were immuno-stained by using an anti-gp96 monoclonal antibody for the expression level of gp96 protein in the sections. In addition, Western blotting of whole cell lysates derived from established human embryonic liver cell lines and several human HCC cell lines (Huh7, HepG2, SSMC-7721) was compared with the expression of gp96. RESULTS: We found that the extent of elevated gp96 expression was significantly correlated with the disease progression, and was the highest in HCC patients, lowest in chronic HBV infection and was that of the cirrhosis in the middle. CONCLUSION: Increased expression of gp96 might be used as a diagnostic or prognostic bio-marker for the HBV infection and HBV-induced diseases.     

GPC3、GS、HSP70在肝细胞癌中的表达及意义

目的研究免疫组织化学套餐磷脂酰肌醇蛋白聚糖-3（glypican-3,GPC3）、热休克蛋白70（heat shock protein70,HSP70）、谷氨酰胺合成酶（glutamyne synthetase,GS）在肝细胞癌（HCC）诊断中的应用。方法对85例HCC进行组织学观察,病理学分级;免疫组织化学方法检测上述病例中GPC3、GS、HSP70的表达情况。结果 85例HCC病例中,GPC3阳性表达率为88.24%（75/85）,GPC3在肝细胞癌的阳性表达率随着分化的升高而递增,高分化与中低分化者GPC3的表达差异有统计学意义,与分化程度相关,其中7例可见癌旁再生结节个别细胞阳性表达;85例中80例HSP70均有不同程度的阳性表达,与HCC分化无明显相关,3例癌周组织中可见汇管区周围肝细胞着色;GS在HCC及周围肝组织的表达方式不同,HCC中有67.06%（57/85）阳性表达,GS的阳性表达与分化无明显相关性。结论 HSP70、GS、GPC3 3个指标的应用对于HCC的诊断具有各自的优点和缺点,在日常工作中,需在HE形态学基础上,结合上述3个指标的分布特点和表达强弱综合评估,免疫组化指标的应用可以进一步提高HCC诊断的可靠性。     

Ursodeoxycholic acid reduces expression of heat shock proteins in primary biliary cirrhosis

BACKGROUND: To identify injured cells in the liver of patients with primary biliary cirrhosis (PBC) and to determine the effects of ursodeoxycholic acid (UDCA) on these cells, we examined the cellular expression of heat shock proteins (HSPs) in PBC both before and after treatment with UDCA. METHODS: Expression of HSP70 and ubiquitin in PBC livers (n=34) was evaluated immunohistochemically as well as by immunoblot analysis, and compared with chronic viral hepatitis type C (n= 9), primary sclerosing cholangitis (n=8), and controls (n=7). RESULTS: Immunoblot analysis demonstrated a marked expression of HSP70 and ubiquitin in PBC. Immunohistochemical staining for both HSP70 and ubiquitin was observed to be strong in biliary epithelial cells (BECs) and moderate in both hepatocytes and arteries in PBC. Cellular labelling rates for HSP70 and ubiquitin of bile ducts in PBC were significantly higher (p<0.01) than those in chronic viral hepatitis type C, primary sclerosing cholangitis, or controls. The labelling rates for HSP70 and ubiquitin in bile ducts and in hepatocytes were significantly decreased (p<0.01) after treatment with UDCA in PBC. CONCLUSIONS: The present data suggest that BECs and hepatocytes significantly express HSPs even in the early stages of PBC, and that UDCA treatment significantly improves their condition. The immunohistochemical evaluation of HSPs is a valid and sensitive means to identify injured cells in PBC.     

肝细胞癌组织中HSP27、VEGF的表达变化及意义

目的观察肝细胞癌（HCC）组织中热休克蛋白27（HSP27）和血管内皮生长因子（VEGF）的表达变化,并探讨其意义。方法采用免疫组化法检测68例HCC组织及癌旁组织中的HSP27、VEGF。结果 HCC组织中HSP27、VEGF阳性表达率分别为75.0%、72.0%,癌旁组织中分别为61.8%、36.8%,两者比较,P均〈0.05。HCC组织中,HSP27表达与乙肝表面抗原（HBsAg）阳性、淋巴结转移、肿瘤分化程度有关（P均〈0.05）,VEGF表达与肿瘤直径、淋巴结转移有关（P均〈0.05）;HCC组织中,HSP27与VEGF的表达呈正相关（r=0.248,P均〈0.05）。结论 HCC组织中HSP27、VEGF表达均升高;二者在HCC发生发展中具有重要作用,检测HSP27、VEGF对HCC的预后判断有一定参考价值。