超重/肥胖合并2型糖尿病患者血清ANGPTL4、HSP70、IL-34水平与胰岛素抵抗的相关性

目的 探讨超重/肥胖合并2型糖尿病(T2DM)患者血清血管生成素样蛋白4(ANGPTL4)、热休克蛋白(HSP)70、白细胞介素-34(IL-34)水平与胰岛素抵抗的相关性。方法 选取2020年5月—2022年5月保定市第一中心医院T2DM患者182例(T2DM组)。参考相关诊断标准,将T2DM患者分为超重/肥胖T2DM组(90例)和体重正常T2DM组(92例)。另选取同期健康体检者90名作为正常对照组,其中超重/肥胖者40名(超重/肥胖对照组)、体重正常者50名(体重正常对照组)。检测所有研究对象血清ANGPTL4、HSP70、IL-34、胰岛素和血糖水平,计算稳态模型胰岛素抵抗指数(HOMA-IR)。T2DM患者治疗3个月后,再次检测其血清ANGPTL4、HSP70、IL-34水平和HOMA-IR。采用Pearson相关分析评估血清ANGPTL4、HSP70、IL-34与HOMA-IR的相关性。结果 与正常对照组和体重正常T2DM组比较,超重/肥胖T2DM组血清ANGPTL4和HSP70显著降低(P<0.05),血清IL-34和HOMA-IR显著升高(P<0.05)。与正常对照组比较,体重正常T2DM组血清ANGPTL4和HSP70显著降低(P<0.05),血清IL-34和HOMA-IR显著升高(P<0.05)。Pearson相关分析结果显示,血清ANGPTL4、HSP70与HOMA-IR呈负相关(r值分别为-0.733、-0.758,P<0.001),IL-34和HOMA-IR呈正相关(r=0.705,P<0.001)。治疗后,超重/肥胖T2DM组和体重正常T2DM组血清ANGPTL4和HSP70均明显升高,血清IL-34和HOMA-IR明显降低;且相对于超重/肥胖T2DM组,体重正常T2DM组血清ANGPTL4和HSP70升高更显著(P<0.05),血清IL-34和HOMA-IR降低更显著(P<0.05)。结论 超重/肥胖合并T2DM患者ANGPTL4、HSP70和IL-34与胰岛素抵抗显著相关,或可作为超重/肥胖合并T2DM的疗效监测指标。

血清CF-6、HSP-70表达对慢性心力衰竭患者病情及预后的评估价值

目的探究血清线粒体偶联因子-6(CF-6)、热休克蛋白70(HSP-70)表达对慢性心力衰竭(CHF)患者病情及预后的评估价值。方法选取2020年12月至2021年12月我院收治的CHF患者106例(CHF组),根据美国纽约心脏病协会(NYHA)心功能分级标准分为:NYHAⅡ级36例(Ⅱ级组),NYHAⅢ级38例(Ⅲ级组),NYHAⅣ级32例(Ⅳ级组);根据预后情况分为预后良好组54例,预后不良组52例;选择同期我院体检健康的106例志愿者为对照组。采用酶联免疫吸附测定(ELISA)法检测血清中CF-6、HSP-70的表达水平;多因素Logistic回归分析影响CHF预后的危险因素;受试者工作特征(ROC)曲线分析血清中CF-6、HSP-70对CHF预后的评估价值。结果与对照组相比,CHF组血清中CF-6、HSP-70表达水平显著升高(P<0.05)。CHF患者Ⅳ级组血清CF-6、HSP-70表达水平显著高于Ⅱ级组和Ⅲ级组,Ⅲ级组表达水平显著高于Ⅱ级组(P<0.05)。与预后良好组相比,预后不良组CF-6、HSP-70水平显著升高(P<0.05)。预后不良组血肌酐水平显著高于预后良好组(P<0.05)。多因素Logistic回归分析显示,CF-6、HSP-70、血肌酐表达水平是影响CHF预后的危险因素;ROC分析显示,血清CF-6、HSP-70水平联合预测CHF预后的AUC高于CF-6、HSP-70单独预测的AUC值(P<0.05)。结论CHF患者血清CF-6、HSP-70表达水平显著升高,并随着病情加重而升高,二者对CHF患者的预后评估有一定的临床价值。

Abrogation of heat-shock protein (HSP)70 expression induced cell growth inhibition and apoptosis in human androgen-independent prostate cancer cell line PC-3m

Aim: To investigate the effect of abrogating heat shock protein (HSP) 70 expression by antisense HSP70 oligonucleotides treatment on human androgen-independent prostate cancer cell line PC-3m growth. Methods: PC-3m cells were treated with 0-16 μmol/L antisense HSP70 oligomers for 0-100 hr. Cell growth inhibition was analyzed using a trypan blue dye exclusion test. Apoptotic cells were detected and confirmed by flow cytometric analysis and DNA fragmentation analysis. The protein expression of HSP70 and bcl-2 affected by antisense HSP70 oligomers were determined using Western blot. Results: Antisense HSP70 oligomer induced apoptosis and then inhibited proliferation of PC-3m cells in a dose- and time-dependent manner. Ladder-like patterns of DNA fragments were observed in PC-3m cells treated with 10 μmol/L antisense HSP70 oligomer for 48 hr or 8 μmol/L for 72 hr on agarose gel electrophoresis. Antisense HSP70 oligomer pretreatment enhanced the subsequent induction of apoptosis by heat shock in PC-3m cells. In addition, undetectable HSP70 expression was observed at a concentration of 10 μmol/L antisense HSP70 oligomer treatment for 48 hr or 8 μmol/L for 72 hr in Western blot, which was paralleled by decreased expression levels of anti-apoptotic protein bcl-2. Conclusion: HSP70 antisense oligomer treatment abrogates the expression of HSP70, which may disrupt HSP70-bcl-2-interactions and further down-regulate bcl-2 expression, in turn inducing apoptosis and inhibiting cell growth in PC-3m cells.

Effect of Ultraviolet Radiation on Hsp70 Protein Expression in HaCaT Cells

Ultraviolet radiation by its wavelength is divided into: UVA, UVB and UVC. Only UVA and UVB manage to penetrate the ozone layer, but due to anthropological activities, all of them are capable of interacting with humans to a greater or lesser extent, and can generate adverse effects such as cellular stress when interacting with intra-and extracellular biomolecules. The skin is the first organ in contact with UV radiation, and the stress it generates can be analyzed by the expression of a bioindicator of cellular damage such as Hsp70. Therefore, the objective of the project was: to determine the effect of UVA, UVB and UVC radiation on HaCaT epithelial cells, by analyzing the expression of Hsp70. Materials and methods: HaCaT cells were cultured in vitro, which were irradiated with UVA, UVB and UVC light at different doses, to subsequently determine the degree of Hsp70 expression by Immunodetection by PAGE-SDS and Western Blot. Results: Basal expression of Hsp70 was observed in no irradiated HaCaT cells. When HaCaT cells were irradiated with UVA, UVB, UVC, an increase in this Hsp70 protein was observed. With UVA, a higher degree of expression was observed at a time of 30 minutes of irradiation. With UVB the highest expression shifted to a time of 20 minutes. With UVC, overexpression was observed after 10 minutes. Conclusion: UV radiation generates cellular stress on HaCaT cells, evaluated by the stress bioindicator Hsp70. According to the wavelength of UV radiation, those that have a shorter wavelength have a greater potential for cellular damage, such as UVC.

血清HSP70、PKD1、YKL-40对绝经后早期子宫内膜癌淋巴结转移的预测效能

目的:探讨血清热休克蛋白70(HSP70)、蛋白激酶D1(PKD1)、甲壳质酶蛋白40(YKL-40)与绝经后早期子宫内膜癌淋巴结转移的关系及预测效能。方法:选取2021年3月至2023年3月中国人民解放军联勤保障部队第九八〇医院收治的126例绝经后早期子宫内膜癌患者(研究组),根据术后病理诊断结果分为淋巴结转移组(n=22)和非淋巴结转移组(n=104)。另选取114例健康体检者作为对照组。比较各组血清HSP70、PKD1和YKL-40水平。采用多因素logistic回归分析方法分析影响患者发生淋巴结转移的因素,受试者工作特征(ROC)曲线分析血清HSP70、PKD1和YKL-40水平对患者淋巴结转移的预测价值。结果:研究组血清HSP70、PKD1和YKL-40水平均高于对照组(P<0.05)。淋巴结转移组患者低分化、子宫肌层浸润≥50%及血清CA125、HE4、HSP70、PKD1和YKL-40水平高于非淋巴结转移组(P<0.05)。多因素logistic回归分析显示,血清HE4、HSP70、PKD1和YKL-40水平及子宫肌层浸润≥50%均为绝经后早期子宫内膜癌患者发生淋巴结转移的独立危险因素(均P<0.05)。血清HSP70、PKD1和YKL-40水平预测绝经后早期子宫内膜癌患者发生淋巴结转移的最佳截断点分别为90.82μg/L、132.23μg/L、75.32μg/L,三者联合预测的灵敏度、特异度和ROC曲线下面积(AUC)分别为81.82%、96.15%、0.940。结论:早期子宫内膜癌患者血清HSP70、PKD1、YKL-40水平可作为预测淋巴结转移的敏感指标,且三者联合预测的预测效能更高。

来曲唑联合地塞米松对多囊卵巢综合征患者血清Galectin-3及HSP70的影响

目的 探讨来曲唑联合地塞米松对多囊卵巢综合征(PCOS)患者血清半乳糖凝集素-3(Galectin-3)及热休克蛋白(HSP70)表达的影响。方法 选择2019年6月—2021年6月在我院治疗的PCOS患者220例为研究对象,按随机数表法分为对照组(n=110)和观察组(n=110),对照组常规给予来曲唑治疗。观察组在对照组的基础上加用地塞米松联合治疗。观察并比较两组患者的激素水平,促排卵情况,血清抗苗勒管激素(AMH)、Galectin-3、HSP70及单核细胞趋化蛋白-1(MCP-1)水平及不良反应发生率。结果 治疗后两组患者的性激素水平均改善,且观察组变化幅度高于对照组(P<0.05)。观察组患者雌二醇(E_(2))用量低于对照组,成熟卵泡数量和最大卵泡直径均高于对照组(均P<0.05)。两组患者的早期流产率差异无统计学意义(P>0.05);观察组患者的妊娠率高于对照组(P<0.05)。治疗前两组患者AMH、Galectin-3、HSP70、MCP-1水平差异无统计学意义(P>0.05),治疗后两组患者的AMH、Galectin-3、HSP70、MCP-1水平均降低,且观察组低于对照组(P<0.05)。观察组和对照组分别有35例和34例出现胃肠道反应、头痛、乳房胀痛等不良反应,两组差异无统计学意义(χ^(2)=0.021,P=0.885)。结论 来曲唑联合地塞米松可能减轻氧化应激反应,减轻胰岛素抵抗,调节激素水平,促进排卵,安全性高,值得推广应用。

原发性肝癌患者高强度聚焦超声治疗前后HSP70、PTN、PIVKA-Ⅱ水平变化及对早期复发的预测效能

目的探究原发性肝癌(PHC)患者在高强度聚焦超声(HIFU)治疗前后热休克蛋白70(HSP70)、多效生长因子(PTN)、异常凝血酶原Ⅱ(PIVKA-Ⅱ)水平变化及对早期复发的影响和预测效能。方法选取2021年1月—2023年1月收治的PHC 120例,均行HIFU治疗,根据术后6个月是否复发分为复发组(26例)与未复发组(94例)。比较2组临床资料、治疗前后血清HSP70、PTN、PIVKA-Ⅱ水平及变化值(ΔHSP70、ΔPTN、ΔPIVKA-Ⅱ值),分析ΔHSP70、ΔPTN、ΔPIVKA-Ⅱ与HIFU治疗后早期复发的相关性,并评价预测效能。结果2组治疗后血清HSP70、PTN、PIVKA-Ⅱ水平较治疗前下降(P<0.05);复发组治疗前、治疗后血清HSP70、PTN、PIVKA-Ⅱ水平高于未复发组(P<0.01)。复发组血清ΔHSP70、ΔPTN、ΔPIVKA-Ⅱ值低于未复发组(P<0.01)。Spearman相关性分析显示,治疗前血清HSP70、PTN、PIVKA-Ⅱ与肿瘤直径、CNLC分期呈正相关,与分化程度呈负相关(P<0.01)。多因素Logistic回归分析显示,校正肿瘤直径、CNLC分期、分化程度因素前后血清ΔHSP70、ΔPTN、ΔPIVKA-Ⅱ值均与PHC患者HIFU治疗后早期复发独立相关(P<0.01);血清ΔHSP70、ΔPTN、ΔPIVKA-Ⅱ值联合预测PHC患者HIFU治疗后早期复发的曲线下面积为0.916(95%CI:0.851,0.958),敏感度为0.923,特异度为0.872,优于三者单独预测。结论PHC患者HIFU治疗前后HSP70、PTN、PIVKA-Ⅱ水平变化值与早期复发独立相关,且联合预测效能较高。

Hcy、HSP70、H-FABP对脑梗死患者的疗效评估作用

目的探讨同型半胱氨酸(Hcy)、热休克蛋白70(HSP70)、心型脂肪酸结合蛋白(H-FABP)对丁苯酞联合通窍活血汤治疗脑梗死患者的疗效评估作用。方法选取鹿邑县人民医院2021年10月至2022年10月收治的82例脑梗死患者作为研究对象,给予丁苯酞联合通窍活血汤治疗。比较有效组和无效组的临床资料及血清学指标,Logistic回归分析影响治疗效果的因素,分析血清Hcy、HSP70、H-FABP单独及联合检测预测治疗效果的价值并编制ROC曲线。结果治疗14 d后,显效38例、有效30例、无效14例,治疗有效率为82.93%。其中有效组68例,无效组14例;有效组Hcy、HSP70、H-FABP水平均低于无效组;Hcy、HSP70、H-FABP均是影响脑梗死患者治疗效果的危险因素;血清Hcy、HSP70、H-FABP联合检测预测治疗效果的AUC值高于单项检测,差异有统计学意义(Z_(Hcy)=3.038,Z_(HSP70)=2.411,Z_(H-FABP)=2.352,P<0.05)。结论血清Hcy、HSP70、H-FABP联合检测对丁苯酞联合通窍活血汤治疗的脑梗死患者的临床疗效具有一定预测价值。

Glutamine supplementation attenuates intestinal apoptosis by inducing heat shock protein 70 in heatstroke rats

BACKGROUND:Heatstroke is the most hazardous heat-related illness and has a high fatality rate.We investigated whether glutamine supplementation could have a protective effect on heatstroke rats.METHODS:Twenty-five 12-week-old male Wistar rats(weight 305±16 g)were randomly divided into a control group(n=5),heatstroke(HS)group(n=10),and heatstroke+glutamine(HSG)group(n=10).Seven days before heat exposure,glutamine(0.4 g/[kg·d])was administered to the rats in the HSG group by gavage every day.Three hours after heat exposure,serum samples were collected to detect white blood cells,coagulation indicators,blood biochemical indicators,and inflammatory cytokines in the rats.The small intestine tissue was stained to analyze pathological structural changes and apoptosis.Finally,immunohistochemistry and Western blotting were used to analyze the expression levels of heat shock protein 70(HSP70).Multiple comparisons were analyzed by using one-way analysis of variance,and the Bonferroni test was conducted for the post hoc comparisons.RESULTS:After heat exposure,the core temperature of the HS group(40.65±0.31°C)was higher than the criterion of heatstroke,whereas the core temperature of the HSG group(39.45±0.14°C)was lower than the criterion.Glutamine supplementation restored the increased white blood cells,coagulation indicators,blood biochemical indicators,and inflammatory cytokines that were induced by heatstroke to normal levels.The intestinal mucosa was injured,and the structure of tight junctions was damaged in the HS group;however,the structure of intestinal mucosal epithelial cells was stable in the HSG group.Glutamine supplementation alleviated intestinal apoptosis and up-regulated HSP70 expression.CONCLUSION:Glutamine supplementation may alleviate intestinal apoptosis by inducing the expression of HSP70 and have a protective effect on heatstroke rats.

老年糖尿病合并肺部感染患者病原菌分布及血清HSP70、HMGB1水平与病情严重程度和预后的关系

目的探讨老年糖尿病合并肺部感染患者病原菌分布情况,分析血清热休克蛋白70(HSP70)、高迁移率族蛋白B1(HMGB1)水平与病情严重程度和预后的关系。方法选择2021年1月—2023年11月西安交通大学第一附属医院呼吸内科与危重症医学科收治的2型糖尿病(T2DM)合并肺部感染患者253例为研究对象,根据出院时预后情况分为预后良好组(n=191)和预后不良组(n=62)。鉴定患者痰液中病原菌并检测血清HSP70和HMGB1水平;采用多因素Logistic回归分析老年T2DM合并肺部感染预后的影响因素;受试者工作特征曲线(ROC)分析血清HSP70和HMGB1水平对老年T2DM合并肺部感染预后的预测价值。结果预后不良组患者年龄、空腹血糖(FPG)、高血压、慢性阻塞性肺疾病(COPD)及病情重度占比显著高于预后良好组(t/χ^(2)/P=6.251/<0.001、14.949/<0.001、4.666/0.031、5.827/0.016、16.530/<0.001)。253例患者痰标本中共检出病原菌株298株,其中革兰阴性菌占比65.10%(194/298)、革兰阳性菌占比28.86%(86/298)、真菌占比6.04%(18/298)。预后不良组血清HSP70和HMGB1水平明显高于预后良好组(t=11.672、13.069,P均<0.001)。血清HSP70和HMGB1水平比较,重度>中度>轻度患者(F=54.146、231.257,P均<0.001);多因素Logistic回归显示,年龄大、HSP70高、HMGB1高、FPG高、COPD及严重程度重均为老年T2DM合并肺部感染预后的危险因素[OR(95%CI)=1.322(1.015~1.722)、1.993(1.336~2.973)、1.754(1.302~2.363)、1.876(1.401~2.512)、3.016(1.798~5.060)、3.956(2.208~7.718)];血清HSP70、HMGB1及二者联合预测老年T2DM合并肺部感染预后的曲线下面积(AUC)分别为0.785、0.772、0.897,二者联合优于各自单独预测效能(Z=3.452、3.297,P均<0.001)。结论血清HSP70、HMGB1水平与老年T2DM合并肺部感染严重程度和预后密切相关,二者联合对其预后具有较高预测价值。

血清HSP60、HSP70水平与原发性免疫性血小板减少症患儿Th17/Treg细胞和预后的关系

目的分析血清热休克蛋白60(HSP60)、热休克蛋白70(HSP70)与原发性免疫性血小板减少症(ITP)患儿辅助性T细胞17/调节性T细胞(Th17/Treg)和预后的关系。方法选取2020年6月—2022年6月保山市人民医院儿科诊治的ITP患儿128例作为病例组,另选同期体检健康儿童60例作为健康对照组。检测并比较2组血清HSP60、HSP70与Th17/Treg细胞水平。Pearson法分析血清HSP60、HSP70与Th17/Treg细胞的相关性。ITP患儿出院后随访1年,根据不同预后情况分为预后良好亚组(107例)和预后不良亚组(21例)。收集ITP患儿的临床资料,采用单因素、多因素Logistic回归模型分析ITP患儿预后的影响因素,并构建风险预测列线图模型。建立受试者工作特征(ROC)曲线分析血清HSP60、HSP70与Th17/Treg细胞对ITP患儿预后的预测价值。结果病例组血清HSP60、HSP70水平及Th17/Treg细胞显著高于健康对照组(t/Z/P=20.445/<0.001、17.467/<0.001、5.823/<0.001)。Pearson相关分析显示,血清HSP60、HSP70与Th17/Treg细胞呈正相关(r/P=0.417/<0.001、0.348/<0.001)。多因素Logistic回归分析显示,HSP60高、HSP70高、Th17/Treg高为ITP患儿预后不良的独立危险因素[OR(95%CI)=1.177(1.041~1.331),1.181(1.038~1.343),9.895(2.171~68.177)],初诊时PLT计数偏高则为保护因素[OR(95%CI)=0.848(0.726~0.990)]。ROC曲线分析结果显示,初诊时PLT、HSP60、HSP70、Th17/Treg水平及列线图模型的曲线AUC分别为0.793、0.730、0.787、0.840、0.975;Bootstrap法(B=1000)对列线图模型进行内部验证显示,Bias-corrected预测曲线与Ideal线基本重合,该模型预测能力较好。决策曲线显示,该模型的阈值概率范围为0.01~0.98,其净收益率>0,高于两条无效线。结论IPT患儿血清HSP60、HSP70、Th17/Treg水平均明显升高,血清HSP60、HSP70与Th17/Treg呈显著正相关。初诊时PLT、HSP60、HSP70、Th17/Treg水平是ITP患儿预后不良的影响因素,且基于HSP60、HSP70等独立危险因素构建的列线图模型对ITP患儿预后不良具有较好的预测价值。

Influence of Tanshinone lla on heat shock protein 70,Bcl-2 and Bax expression in rats with spinal ischemia/reperfusion injury

Tanshinone lla is an effective monomer component of Danshen, which is a traditional Chinese medicine for activating blood circulation to dissipate blood stasis. Tanshinone Ila can effectively improve brain tissue ischemia/hypoxia injury. The present study established a rat model of spinal cord ischemia/reperfusion injury and intraperitoneally injected Tanshinone lla, 0.5 hour prior to model establishment. Results showed that Tanshinone Ila promoted heat shock protein 70 and Bcl-2 protein expression, but inhibited Bax protein expression in the injured spinal cord after ischemia/reperfusion injury. Furthermore, Nissl staining indicated a reduction in nerve cell apoptosis and fewer pathological lesions in the presence of Tanshinone Ila, compared with positive control Danshen injection.

Purification of heat shock protein 70-associated tumor peptides and their antitumor immunity to hepatoma in mice

AIM:To purify the heat shock protein (HSP) 70-associated tumor peptides and to observe its non-MHC-I molecule restrictive antitumor effect.METHODS:By ConA-sepharose affinity chromatography,ADP-agarose affinity chromatography, and DEAE anion exchange chromatography, we were able to purify HSP70-associated peptides from mouse hepatoma (HCaF) cells treated in heat shock at 42℃. Specific active immunization and adoptive cellular immunization assay were adopted to observe the immunoprotective effect elicited by HSP70-associated peptide complexes isolated from HcaF.RESULTS: The finally purified HSP-associated peptides had a very high purity and specificity found by SDS-PAGE and Western blot. Mice immunized with HSP70-associated peptide complexes purified from HCaF cells were protected from HCaF living cell challenge. This effect was dose dependent.Adoptive immunization of immune spleen cells of mice immunized with HSP70-associated peptide complexes could elicit immunity against HCaF challenge, and the tumor-free mice could resist repeated challenges. This effect could be continuously enhanced by repeated challenge with HCaF living cells. The tumor-free mice could tolerate the challenge for as high as 1×10^7 HCaF cells. The mice immunized once with spleen cells pulsed with HSP70-associated peptide complexes in vitro could also result in a certain adoptive immunity against HCaF.CONCLUSION:High purity and specificity of HSP70-associated peptides could be achieved from tumor cells by the low-pressure affinity chromatography method used in this study. HSP70-associated peptide complexes derived from the HCaF can elicit non-MHC-I molecule restrictive immunoprotective effect against HCaF.This effect can be transferred by adoptive immunization to mice and enhanced by repeated challenge with HCaF live cells.

Radiofrequency ablation,heat shock protein 70 and potential anti-tumor immunity in hepatic and pancreatic cancers:a minireview

BACKGROUND: Radiofrequency ablation (RFA) is a minimally invasive surgical procedure which has widespread popularity in the treatment of hepatic and pancreatic cancers. Increased evidence indicates that RFA stimulates anti-tumor immunity, possibly through the induction heat shock protein 70 (HSP70) expression. HSP70 has the capacity to affect the immunogenicity of tumor cells, to chaperone antigenic peptides and deliver these into antigen presentation pathways within antigen-presenting cells, and to activate and regulate innate and adaptive immunity, which makes it useful in immunotherapeutic strategies for the treatment of cancers. DATA SOURCES: An English-language literature search was conducted using MEDLINE (1991-2010) on anti-tumor immunity, heat shock protein 70, radiofrequency ablation, hepatic cancer, pancreatic cancer, and other related subjects. RESULTS: RFA has an increasing application in the surgical treatment of hepatic and pancreatic cancers. Increased evidence indicates that RFA can induce the expression of HSP70 which possesses properties that enable it to influence a variety of immunological processes. Tumor-derived HSP70 is regarded as a potent adjuvant facilitating presentation of tumor antigens and induction of anti-tumor immunity. CONCLUSIONS: This review addresses the potential association of RFA, HSP70, and anti-tumor immunity in treatment of hepatic and pancreatic cancers. To establish direct evidence of a potential association of RFA, HSP70, and anti-tumor immunity in hepatic and pancreatic cancers, further investigations should be conducted.

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 esophageal carcinoma and adjacent normal tissues.METHODS: The expression of HSP70 and grp94 in 78human esophageal cancer and adjacent normal tissues was studied by immunohistochemistry and pathology photograph analysis.RESULTS: Both esophageal cancer and adjacent normal tissues could express HSP70 and grp94. Of the 78 cases of esophageal 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 esophageal 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 HSP70is related to the differentiation of esophageal carcinoma.

Correlation between clinicopathology and expression of heat shock protein 70 and glucose-regulated protein 94 in human colonic adenocarcinoma

AIM: To investigate the correlation between dinicopathology and expression of heat shock protein 70 (HSP70) and glucose-regulated protein 94 (grp94) in human colonic carcinoma.METHODS: The expression of HSP70 and grp94 was studied in 80 human colonic cancers with or without metastasis as well as in their adjacent mucous membrane by way of immunohistochemistry and pathology photograph analysis.RESULTS: The expression of HSP70 and grp94 was significantly higher in cancer than that in adjacent mucous membrane (92.5%, 85.0% vs 56.3%, 42.5%, P＜0.01).HSP70 and grp94 expressed higher in moderately- and poorly-differentiated colonic cancers than that in their adjacent tissues (93.7%, 87.5%; 100%, 90% vs 56.3%,42.5%; P＜0.01). Dukes C and D stages of colonic cancers showed higher positive rates than Dukes A and B stage groups (97.1%, 91.2%; 100%, 90.9%; vs 80%, 70%;78.6%, 71.4%; P＜0.05). There were definite differences in HSP70 and grp94 expression between metastasis groups and non-metastasis groups (100% vs75%, 100%vs 50%, P＜0.05).CONCLUSION: The HSP70 and grp94 expression rates in colonic cancer groups are significantly higher than that in their adjacent mucous membrane. The HSP70 and grp94expression in poorly-differentiated colonic cancers with metastasis is significantly higher than well-differentiated cancers without metastasis. The overexpression of HSP70and grp94 can be used as diagnostic or prognostic markers for colonic cancer.

Heat shock protein 70 antisense oligonucleotide inhibits cell growth and induces apoptosis in human gastric cancer cell line SGC-7901

AIM: Heat shock protein (HSP)70 is over-expressed in human gastric cancer and plays an important role in the progression of this cancer. We investigated the effects of antisense HSP70 oligomer on human gastric cancer cell line SGC-7901, and its potential role in gene therapy for this cancer.METHODS: Human gastric cancer cell line SGC-7901 was treated in vitro with various concentrations of antisense HSP70 oligonucleotides at different intervals. Growth inhibition was determined as percentage by trypan blue dye exclusion test. Extracted DNA was electrophoresed on agarose gel, and distribution of cell cycle and kinetics of apoptosis induction were analyzed by propidium iodide DNA incorporation using flow cytometry, which was also used to detect the effects of antisense oligomer pretreatment on the subsequent apoptosis induced by heat shock in SGC-7901 cells. Proteins were extracted for simultaneous measurement of HSP70 expression level by SDS-PAGE Western blotting.RESULTS: The number of viable cells decreased in a doseand time-dependent manner, and ladder-like patterns of DNA fragments were observed in SGC-7901 cells treated with antisense HSP70 oligomers at a concentration of 10 μmol/L for 48 h or 8 μmol/L for 72 h, which were consistent with inter-nucleosomal DNA fragmentation. Flow cytometric analysis showed a dose- and time-dependent increase in apoptotic rate by HSP70 antisense oligomers. This response was accompanied with a decrease in the percentage of cells in the G1 and S phases of the cell cycle, suggesting inhibition of cell proliferation. In addition, flow cytometry also showed that pretreatment of SGC-7901 cells with HSP70 antisense oligomers enhanced the subsequent apoptosis induced by heat shock treatment. Western blotting demonstrated that HSP70 antisense oligomers inhibited HSP70 expression, which preceded apoptosis, and HSP70 was undetectable at the concentration of 10 μmol/L for 48 h or 8 μmol/L for 72 h.CONCLUSION: Antisense HSP70 oligomers can abrogate HSP70 expression in SGC-7901 cells, which may in turn induce apoptosis and inhibit cell proliferation, conversely suggesting that HSP70 is required for the proliferation and survival of human gastric cancer cells under normal conditions.

Expression of Heat Shock Protein 70 and 27 in Non-small Cell Lung Cancer and Its Clinical Significance

The heat shock proteins （HSPs） 70 and HSP 27 expression in patients with non-small cell lung cancer （NSCLC） was studied and the relation.ship between HSP 70 and HSP 27 with the clinicopathological features of NSCLC was investigated. The expression of HSP 70 and HSP 27 was detected in tumor tissues from 60 patients with NSCLC by S-P immunohistochemistry. The findings were analyzed in combination with the histological types, histopathological differentiation, lymph node metastasis, patients＇ clinical stages, smoking history and gender. The results showed that of the 60 NSCLC tissue specimens studied, the immunoreactivity of HSP 70 and HSP 27 was detected in 47 （78.3 %） and 43 （71.7 %） specimens, respectively. A positive correlation was found between the overexpression of HSP 70 and HSP 27. The histopathological differentiation, lymph node metastasis, clinical stages and smoking history were correlated to the expression of HSP 70, but not to the expression of HSP 27. No statistical significance was observed in histological types and gender with respect to both HSP 70 and HSP 27 expression. It is suggested that the HSP 70 expression is a powerful and significant prognostic indicator and is related to histopathological differentiation, lymph node metastasis, patients＇ clinical stages, smoking history, whereas HSP 27 expression is not.

Co-expression of heat shock protein 70 and glucose-regulated protein 94 in human gastric carcinoma cell line BGC-823

AIM: To investigate the co-expression and significance of heat shock protein 70 (HSP70) and glucose-regulatedprotein 94 (grp94) in human gastric carcinoma cell line BGC-823.METHODS: The expression and localization of HSP70 and grp94 in human gastric carcinoma cell line BGC-823 were determined by immunocytochemistry and indirect immunofiuorescence cytochemical staining. Flow cytometry was used to analyze the correlation between expression of HSP70, grpg4 and cell cycle in BGC-823 cell line.RESULTS: Gastric cancer cell line BGC-823 expressed high level of HSP70 and grp94. The positive rate of HSP70 and grp94 was 84.9±4.94% and 79.6±5.16%, respectively. Bothof them were stained in cell plasma. There was a significant difference compared with control group (1.9±0.94%,P＜0.01). During the cell cycle, HSP70 and grp94 were continuously expressed in BGC-823.CONCLUSION: HSP70 and grp94 are highly expressed in human gastric carcinoma BGC-823 cells through the whole cell cycle. There is no relationship between expression of HSP70, grp94 and cell cycle.

Heat shock protein 70 chaperoned alpha-fetoprotein in human hepatocellular carcinoma cell line BEL-7402

AIM: To investigate the interaction between heat shock protein 70 (HSP70) and α-fetoprotein (AFP) in human hepatocellular carcinoma (HCC) cell line BEL7402.METHODS: The expression and localization of HSP70 and AFP in human HCC cell line BEL-7402 were determined by immunocytochemistry and indirect immunofluorescence cytochemical staining. The interaction between HSP70 and AFP in HCC cells was analyzed by immunoprecipitation and Western blot.RESULTS: Immunocytochemical staining detection showed that HCC cell BEL-7402 expressed a high level of HSP70 and AFP synchronously. Both were stained in cell plasma.AFP existed in the immunoprecipitate of anti-HSP70 mAb,while there was HSP70 in the immunoprecipitate of antiAFP mAb.CONCLUSION: HSP70 chaperones AFP in human HCCcell BEL-7402. The interaction between HSP70 and AFP in human HCC cell can be a new route to study the pathogenesis and immunotherapy of HCC.