四种热休克蛋白/肽混合物预防小鼠肉瘤发生、发展的作用研究

目的 探讨四种热休克蛋白(heat shock protein,HSP)/肽混合物防治小鼠肉瘤的作用及其机制.方法 小鼠S180肉瘤及MCA-207肉瘤组织,分别剪碎,裂解,离心,取上清上Sephacryl S-200HR层析柱,截取相对分子质量相当于50×10~3～200×10~3段,再经Con A、ADP亲和层析,SDS-PAGE电泳及Western-blot鉴定.分别用HSP-70、HSP-60及热休克蛋白/肽混合物(HSP-70、HSP-60、HSP-110、Gp-96)免疫小鼠,观察无瘤生存率、抑瘤生长率及存活期.用流氏细胞仪检测"T"细胞亚群,ELISPOT检测IFN-γ,乳酸脱氢酶检测混合淋巴细胞杀伤作用等方法观察免疫功能的变化.结果 HSP-70、HSP-60及热休克蛋白/肽混合物均有预防性免疫治疗效果,热休克蛋白/肽混合物防治S180肉瘤达到41.2%的无瘤长期生存,抑瘤生长率为83.3%,优于单一的HSP哑型.热休克蛋白/肽混合物防治MCA肉瘤达到50.0%的无瘤长期生存,抑瘤生长率为79.0%;多种方法检测表明热休克蛋白/肽混合物疫苗可诱发小鼠的细胞免疫功能.结论 热休克蛋白/肽混合物可诱发机体细胞的免疫功能,其抑制肉瘤生长效果优于单一的HSP-70或HSP-60,具有临床应用前景.     

混合热休克蛋白/肽复合物疫苗疫防治小鼠肉瘤

我们从肿瘤细胞提取的不同类型的HSPs／肽复合物对小鼠S180肉瘤模型进行了免疫防治研究。现将结果报道如下。     

热休克蛋白27、70与恶性肿瘤

热休克蛋白(heat shock protein,HSP)广泛存在于生物体内,是一类在进化上高度保守的细胞应激蛋白.其中HSP27和HSP70在抗凋亡过程中发挥重要的作用,在多种肿瘤细胞中异常高表达,尤其是腺癌起源的肿瘤.HSP27和HSP70在恶性肿瘤的发生、发展中的作用及其机制是近年来研究的热点,有望对肿瘤的治疗提供新的平台.     

热休克蛋白90与前列腺癌

雄激素阻断疗法虽然对前列腺癌有显著疗效,但是大多数肿瘤仍会进展为雄激素非依赖性生长阶段.分子伴侣热休克蛋白90的多种底物蛋白与前列腺癌的发生、发展密切相关.以热休克蛋白90作为治疗靶点,能够同时阻断对前列腺癌生长具有重要作用的多条信号通路,为前列腺癌的治疗提供新的思路.     

热休克蛋白90与前列腺癌

雄激素阻断疗法虽然对前列腺癌有显著疗效,但是大多数肿瘤仍会进展为雄激素非依赖性生长阶段。分子伴侣热休克蛋白90的多种底物蛋白与前列腺癌的发生、发展密切相关。以热休克蛋白90作为治疗靶点,能够同时阻断对前列腺癌生长具有重要作用的多条信号通路,为前列腺癌的治疗提供新的思路。     

应用热休克蛋白/肽复合物疫苗防治肿瘤

肿瘤手术切除后能否根治 ,最关键的是防止复发和转移 ,目前所用的化疗或放疗往往不仅杀死了肿瘤细胞 ,也摧毁了机体的免疫功能 ,最终难以根治。如何调动机体的免疫功能来杀伤肿瘤细胞是人们长期以来的设想 ,这方面的研究持续了百年的历史 ,仅在近 10余年来 ,随着免疫学和分子生物学等基础医学的突破性进展 ,开始展现了调动机体特异性免疫功能杀伤肿瘤细胞 (肿瘤疫苗 )的可喜的苗头。机体能识别和杀灭非我的外来微生物 ,而不能消灭自身的肿瘤 ,这一现象归结为肿瘤细胞逃逸了机体的免疫监视。因此 ,长期以来人们从事于两个方面的研究 ,一是肿…     

热休克蛋白gp96与肾癌

热休克蛋白gp96(HSPgp96)是一种高度保守和呈单态性的蛋白质。它能与细胞内大量多肽非共价结合 ,参与MHCⅠ类抗原的提呈。用肿瘤源HSPgp96 肽复合物免疫小鼠可诱发抗相应肿瘤细胞的MHCⅠ类限制性CD8+ 细胞毒性T细胞免疫应答 ,并能产生记忆性T细胞应答 ,具备了作为疫苗的一个关键要素 ,为肿瘤免疫治疗开辟了一个新的途径。本文对HSPgp96与肾癌免疫治疗的研究作一概述。     

热休克蛋白47与肾脏纤维化

热休克蛋白47(HSP47)是胶原特异性“分子伴侣”，可能在不同器官的纤维化进程中起重要作用。本文综述了HSP47的基因结构、分子特点、功能及在肾脏纤维化中的作用。     

热休克因子1及其与热休克蛋白表达的关系研究进展

This article reviews the advances in the research of the structural characteristics and the activating process of heat shock factor 1(HSF-1),the factors that influence the expression of HSF-1,and the r...     

热休克蛋白家族与肿瘤的相关性及其临床应用的研究进展

热休克蛋白是一组应激蛋白,在多数肿瘤细胞中表达增高,并参与肿瘤的生长、侵袭、转移等,与患者预后密切相关。本文就HSPs的特点、功能、与肿瘤发生发展的关系及临床应用分别进行介绍,深入了解和认识热休克蛋白与肿瘤之间发生作用的机制和规律,对研究肿瘤的防治策略具有重要意义。     

热休克蛋白在子宫颈癌中的表达及其意义

目的探讨热休克蛋白(heat shock proteins,HSPs)在子宫颈癌组织中的表达情况及意义。方法采用PT—PCRH和免疫印迹法检测HSPs在子宫颈癌组织及正常子宫组织中的蛋白和mRNA的表达水平。结果癌组织中HSP70、HSP86及αB晶状体蛋白表达较正常组织明显增多(P<0.05),且HSP70表达最高(P<0.01)。结论 HSP70在子宫颈癌组织中表达显著增高。     

ATPase inhibition by omeprazole reveals role of heat shock proteins on testicular torsion

Testicular torsion leads ischaemic injury and generates reactive oxygen species. Reactive oxygen species triggers lipid peroxidation, protein degradation and DNA damage. These biochemical processes trigger tissue damage. Heat shock proteins (HSPs) are important in spermatogenesis, and this work elucidates role of HSPs at the testicular torsion–detorsion process. A proton-pump inhibitor, omeprazole, tested to reveal the drug's curative effect since HSP functions through ATP hydrolysis. Thirty-two male Wistar Albino rats were divided into four groups: sham, control, omeprazole and serum physiologic groups. Right testis was torsed, while left ones remained untorsed. Protein peroxidation, DNA damage and lipid hydroperoxide levels as well as HSP expression were measured. Further, the effects were visualised with histopathologic imaging. HSP expression increases at the torsed right testis compared to the contralateral testis. Although HSP70 and HSP90 help antioxidant enzymes to keep their native structure, their anti-apoptotic properties accelerate the tissue damage. Omeprazole a proton-pump inhibitor employed to impair electron transfer chain and to inhibit HSP ATPase function. Omeprazole effectively inhibits HSPs and alleviates lipid peroxidation and DNA damage levels both at molecular and at tissue level, and the drug has profound curative effect on testicular torsion recovery.     

热休克蛋白在肝细胞癌形成、增殖、复发、转移及抗肿瘤免疫中的作用研究

【摘要】 热休克蛋白(heat shock proteins, HSPs)是一类结构高度保守的蛋白质,主要参与蛋白的转运、折叠、维持蛋白质自身稳定及免疫应答。大量研究表明,HSPs中多个成员如HSP27、HSP70及HSP90,在肝细胞癌(hepatocellular carcinoma, HCC)中呈过表达。本文就HSPs在肝细胞癌的形成、增殖、复发、转移及抗肿瘤免疫的作用进行综述。     

O-ClcNAc修饰在谷氨酰胺诱导内毒素休克大鼠心肌组织HSP70表达中的作用

目的 探讨O位-N-乙酰葡糖胺(O-GlcNAc)修饰在谷氨酰胺诱导内毒素休克大鼠心肌组织热休克蛋白70(HSP70)表达中的作用.方法 健康雄性SD大鼠32只,随机分为4组(n=8),正常对照组(C组)仅静脉输注乳酸钠林格氏液;LPS组、G+LPS组和A+G+LPS组均静脉注射LPS10 mg/kg,G+LPS组给予LPS前1 h静脉注射谷氨酰胺0.75 g/kg,A+G+LPS组给予LPS前1h依次静脉注射谷氨酰胺0.75 g/kg和O-位-N-乙酰葡萄糖胺糖基转移酶抑制剂四氧嘧啶50 mg/kg.注射LPS后6 h处死大鼠,取心肌组织,测定O-GlcNAc和HSP70的表达水平.结果 与C比较,其他各组心肌O-GlcNAc和HSP70的表达水平均上调(P＜0.05);与LPS组比较,G+LPS组心肌O-GlcNAc和HSP70的表达水平上调(P＜0.05);与G+LPS组比较,A+G+LPS组心肌O-GlcNAc和HSP70的表达水平下调(P＜0.05).结论 O-GlcNAc修饰参与了谷氨酰胺诱导内毒素休克大鼠心肌HSP70表达上调.     

The role of heat shock proteins in reproduction

Heat shock proteins (hsp) were first discovered in cells exposed to elevated temperature. They are preferentially expressed in response to an array of insults, including hyperthermia, free oxygen radicals, heavy metals, inflammation and infection. In addition hsp are involved in several processes essential for cellular function under physiological conditions. Heat shock proteins are expressed during oogenesis and spermatogenesis. In the early stages of the pregnancy they are expressed both in embryo and maternal decidua. Antibodies to bacterial and human hsp are present at high titers in serum of many patients undergoing in vitro fertilization. Several studies provided evidence that immune sensitization to hsp is associated with unsuccessful embryo development and implantation failure in in-vitro-fertilization (IVF) patients.     

中药对烧伤患者免疫功能及急性期蛋白的影响

目的观察中药对伤后细胞免疫功能和４种急性期反应蛋白（ＡＲＰ）的作用。方法在过去动物实验的基础上,将中药配伍后用于烧伤患者。结果能使受损严重的患者淋巴细胞增殖反应及白细胞介素２产生能力,得到显著的改善。对伤后患者血中变化的触珠蛋白、前白蛋白、α１酸性糖蛋白和转铁蛋白均有不同程度的影响。结论中药合用对烧伤患者失衡的免疫防御系统功能和ＡＲＰ具有调理功效     

Expression of major heat shock proteins in prostate cancer: correlation with clinicopathological outcomes in patients undergoing radical prostatectomy

PURPOSE: We evaluated expression levels of major heat shock proteins in radical prostatectomy specimens to clarify the significance of heat shock protein expression in prostate cancer. MATERIALS AND METHODS: Expression levels of heat shock proteins 27, 70 and 90 in radical prostatectomy specimens from 172 patients with clinically organ confined prostate cancer who had not received neoadjuvant hormonal therapy were measured by immunohistochemical staining. Cell proliferative activities and apoptotic features in these specimens were investigated using Ki-67 immunostaining and TUNEL assay, respectively. These findings were analyzed with respect to several clinicopathological factors. RESULTS: Various levels of heat shock protein 27 expression were noted in all prostate cancer specimens. Expression levels of heat shock protein 27 in prostate cancer tissues was significantly associated with pathological stage, Gleason score, surgical margin status, lymph node metastasis and tumor volume but not with other parameters, including patient age, serum prostate specific antigen and perineural invasion. Similarly most prostate cancer tissues showed heat shock protein 70 and 90 expression. However, there was no significant correlation between expression levels of these 2 heat shock proteins and several clinicopathological factors examined. Cell proliferative activity in prostate cancer specimens was significantly associated with heat shock protein 27 expression but not with that of heat shock proteins 70 and 90, while there was no significant correlation between the apoptotic index and the expression of these 3 heat shock proteins. Furthermore, despite the lack of prognostic significance in heat shock proteins 70 and 90 expression, biochemical recurrence-free survival in patients with strong heat shock protein 27 expression in radical prostatectomy specimens was significantly lower than that in those with weak heat shock protein 27 expression. However, multivariate analysis showed that strong heat shock protein 27 expression could not be an independent predictor of biochemical recurrence after radical prostatectomy. CONCLUSIONS: These findings suggest that, despite the limited significance of heat shock proteins 70 and 90 expression, heat shock protein 27 may be involved in the progression of prostate cancer. The expression level of heat shock protein 27 in prostate cancer tissue could be used as a useful predictor of biochemical recurrence in patients undergoing radical prostatectomy.     

Role of heat shock proteins in the pathogenesis of cystic fibrosis arthritis

BACKGROUND: Arthritis is a well recognised complication of cystic fibrosis. The cause of this arthritis is not yet clear but it is likely to be an immunological reaction to one of the many bacterial antigens to which the lungs are exposed. One such group, the heat shock proteins, (hsp), was investigated. These are immunodominant antigens of a wide variety of infectious microorganisms and have varying amino acid chain sequences, some of which are similar to those found in human tissues. METHODS: Antibodies to human hsp 27 and hsp 90 in the serum of patients with cystic fibrosis, with and without arthritis, and in normal age and sex matched healthy controls were measured. The severity of the cystic fibrosis was assessed by lung function tests and chest radiographs. The nature of the organisms colonising the lungs was determined by bacteriological examination of sputum. RESULTS: Higher mean titres of serum IgG anti-human hsp 27 and hsp 90 antibodies were found in 50 patients with cystic fibrosis than in healthy controls (hsp 27, 0.25 (95% CI 0.19 to 0.33) versus 0.05 (95% CI 0.04 to 0.07); hsp 90, 0.27 (95% CI 0.22 to 0.32) versus 0.11 (95% CI 0.08 to 0.14)). These antibodies were higher in patients in whom the lungs were colonised with Pseudomonas aeruginosa than in those without infection (hsp 27, 0.41 (95% CI 0.17 to 0.63) versus 0.18 (95% CI 0.10 to 0.27); hsp 90, 0.37 (95% CI 0.18 to 0.57) versus 0.22 (95% CI 0.16 to 0.29)). The eight patients with cystic fibrosis with arthritis had higher anti- hsp 27 antibodies (0.48 (95% CI 0.13 to 0.92)) than the 42 patients without arthritis (0.22 (95% CI 0.17 to 0.30)). CONCLUSIONS: These findings suggest that the arthritis associated with cystic fibrosis, despite being seronegative for rheumatoid factor, was associated with more severe lung disease and with a greater inflammatory response to heat shock proteins.