HSP70在骨巨细胞瘤中的表达及其意义的研究
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摘要
目的检测热休克蛋白70(HSP70)在骨巨细胞瘤中的表达，探讨其与骨巨细胞瘤Jaffe病理分级和Enneking外科分期的关系，给临床诊断治疗提供帮助。
方法收集30例骨巨细胞瘤患者的手术标本，与10例骨软骨瘤进行对照，采用免疫组化S—P法检测HSP70在不同肿瘤中的表达情况，分析其与骨巨细胞瘤分期的关系。
结果
1．HSP70在骨巨细胞瘤组中表达高于骨软骨瘤组，二者有显著差异(P＜0.05)。
2．按照Enneking外科分期：(1)．HSP70在骨巨细胞瘤1级组与骨软骨瘤组中的表达无差异性(P=1.000)，无统计学意义；(2)．HSP70在骨巨细胞瘤2级组和3级组中表达均显著高于骨软骨瘤组中表达(P＜0.05)；(3)．HSP70在骨巨细胞瘤2级组和3级组中表达均显著高于骨巨细胞瘤1级组(P＜0.05)；(4)．HSP70在骨巨细胞瘤2级组与骨巨细胞瘤3级组中表达差异性不显著(P＞0.05)。
3．按照Jaffe分级，HSP70在骨巨细胞瘤3级组中表达与骨巨细胞瘤1级&2级组差异性不显著(P＞0.05)。
结论
1．HSP70在骨巨细胞瘤中表达显著高于骨软骨瘤，认为HSP70可能在骨巨细胞瘤发生发展中起作用。
2．Enneking外科分期中，HSP70阳性表达率在骨巨细胞瘤2、3级显著高于骨巨细胞瘤1级，且差异有统计学意义，认为HSP70可作为判定骨巨细胞瘤侵袭性辅助指标。
3．HSP70表达对于骨巨细胞瘤Jaffe病理分级无指导意义。
OBJECTIVE In order to guide the treatment of GCT, this study is aimed to investigate the relation between the expression of HSP70 in GCT and classification (Jaffe & Enneking), by detecting expression of HSP70.
METHODS 30 cases of GCT were collected including surgical operation spcimens,10 cases of osteochondroma were taken as control group. we detected the exprssion of HSP70 ,and analyzed the relation between the expression of HSP70 and classification(Jaffe & Enneking) of GCT.
RESULTS
1.The expression of HSP70 was significantly higher in GCT group than osteochondroma group,P<0.05.
2.According to Enneking Grade: (1) .There was no statistical significance in the expression of HSP70 between GCT 1 group and osteochondroma group,P=1.000; (2) .The expression of HSP70 were significantly higher in both GCT 2 and GCT 3 group than osteochondroma group,P<0.05; (3) .The expression of HSP70 were significantly higher in both GCT 2 and GCT 3 group than GCT 1 group,P<0.05;(4). There was no significant difference in the expression of HSP70 between GCT 2 group and GCT 3 group,P>0.05.
3.According to Jaffe Grade, There was no significant difference in the expression of HSP70 between GCT 3 group and GCT 1 & 2 group, P>0.05.
CONCLUSION
1.The expression of HSP70 in GCT is higher than osteochondroma , there is statistical significance ,HSP70 play a role in the occurence and develop course of GCT.
2.On the premise of Enneking Grade,there is statistical significance between GCT 1 group and GCT 2, 3 groups in the expression of HSP70.The expression of HSP70 can indicated the invasion of giant cell tumor of bone.
3.The expression of HSP70 is of no use for Jaffe Grade in GCT.
方法收集30例骨巨细胞瘤患者的手术标本，与10例骨软骨瘤进行对照，采用免疫组化S—P法检测HSP70在不同肿瘤中的表达情况，分析其与骨巨细胞瘤分期的关系。
结果
1．HSP70在骨巨细胞瘤组中表达高于骨软骨瘤组，二者有显著差异(P＜0.05)。
2．按照Enneking外科分期：(1)．HSP70在骨巨细胞瘤1级组与骨软骨瘤组中的表达无差异性(P=1.000)，无统计学意义；(2)．HSP70在骨巨细胞瘤2级组和3级组中表达均显著高于骨软骨瘤组中表达(P＜0.05)；(3)．HSP70在骨巨细胞瘤2级组和3级组中表达均显著高于骨巨细胞瘤1级组(P＜0.05)；(4)．HSP70在骨巨细胞瘤2级组与骨巨细胞瘤3级组中表达差异性不显著(P＞0.05)。
3．按照Jaffe分级，HSP70在骨巨细胞瘤3级组中表达与骨巨细胞瘤1级&2级组差异性不显著(P＞0.05)。
结论
1．HSP70在骨巨细胞瘤中表达显著高于骨软骨瘤，认为HSP70可能在骨巨细胞瘤发生发展中起作用。
2．Enneking外科分期中，HSP70阳性表达率在骨巨细胞瘤2、3级显著高于骨巨细胞瘤1级，且差异有统计学意义，认为HSP70可作为判定骨巨细胞瘤侵袭性辅助指标。
3．HSP70表达对于骨巨细胞瘤Jaffe病理分级无指导意义。
OBJECTIVE In order to guide the treatment of GCT, this study is aimed to investigate the relation between the expression of HSP70 in GCT and classification (Jaffe & Enneking), by detecting expression of HSP70.
METHODS 30 cases of GCT were collected including surgical operation spcimens,10 cases of osteochondroma were taken as control group. we detected the exprssion of HSP70 ,and analyzed the relation between the expression of HSP70 and classification(Jaffe & Enneking) of GCT.
RESULTS
1.The expression of HSP70 was significantly higher in GCT group than osteochondroma group,P<0.05.
2.According to Enneking Grade: (1) .There was no statistical significance in the expression of HSP70 between GCT 1 group and osteochondroma group,P=1.000; (2) .The expression of HSP70 were significantly higher in both GCT 2 and GCT 3 group than osteochondroma group,P<0.05; (3) .The expression of HSP70 were significantly higher in both GCT 2 and GCT 3 group than GCT 1 group,P<0.05;(4). There was no significant difference in the expression of HSP70 between GCT 2 group and GCT 3 group,P>0.05.
3.According to Jaffe Grade, There was no significant difference in the expression of HSP70 between GCT 3 group and GCT 1 & 2 group, P>0.05.
CONCLUSION
1.The expression of HSP70 in GCT is higher than osteochondroma , there is statistical significance ,HSP70 play a role in the occurence and develop course of GCT.
2.On the premise of Enneking Grade,there is statistical significance between GCT 1 group and GCT 2, 3 groups in the expression of HSP70.The expression of HSP70 can indicated the invasion of giant cell tumor of bone.
3.The expression of HSP70 is of no use for Jaffe Grade in GCT.
引文
[1] Fletcher CDM,Unni KK, Mertens F.Pathology and genetics of tumors of soft tissue and bone [M]. World Health Organization Classification of Tumors.Lyon:IARC Press. 2002, 210.
[2] Saiz P, Virkus W, Piasecki P, et al. Results of giant cell tumor of bone treated with intralesional excision. Clin Orthop, 2004, (424) :221-226.
[3] Sung HW, Kuo DP, Shu WP,et al.Giant cell tumor of bone: analysis of two hundred and eight cases in chinese patients. J Bone Joint Surg, 1982,64-A:755-761.
[4] Mcdonald DJ, Sin FH, Mcleod RA, et al.Giant cell tumor. J Bone Joint Surg, 1986,68-A:235-242.
[5] Campacci M, Baldini N, Boriani S, et al.Giant cell tumor of bone. J Bone Joint Surg, 1987,69-A:106-113.
[6] 周建伟，姜建元．骨巨细胞瘤的治疗．中华肿瘤杂志，1990，12：389-391．
[7] Schwartz HS.Update on giant cell tumor of one. ComprTher, 1998, 24(10):488-493.
[8] Koyasuu S,N is hidaE ,KadoeakiT, et al. Two mammalian heat shock proteins,HSP90 and HSP100,are actin-binding proteins. Pro Natl Acad Sci U SA, 1986, 83: 8054-8058.
[9] 曲军，祝学光，顾晋，等．HSP70mRNA在大肠癌中的高表达及其临床意义．中华实外科杂志，1998，15(6)：559-560．
[10] 徐先发，赵玫，施一江，等．热休克蛋白在喉癌中的表达．中华耳鼻喉科杂志，1998，33(4)：232-234．
[11] 李淳，程继东，蔡维佳，等．热休克蛋白70在食管鳞癌中的表达．汕头大学医学院学报，1998，11：5-6．
[12] 内藤善哉，乔炎，浅野五郎．热休克蛋白在乳腺癌中的作用．中华病理学杂志，1998．27：35-39．
[13] Sugahara K, Yamada Y, Hiragata Y,et al.Soluble and membrane isoforms of Fas/CD95 in fresh adult T-cell leukemia (ATL) cells and ATL-cell lines. Int J Cancer, 1997,72:128-132.
[14] Munker R, Midis G, Owen-Schanb L, et al.Soluble Fas (CD95) is not elevated in the serum of patients with myeloid leukemias, myeloproliferative and yelodysplastie syndromes.Leukemia, 1996,10:1531-1533.
[15] Present D, Bertoni F, Hundson T,et al.The correlation between the radiologic staging studies and histopathologic findings in aggressive stage 3 giant cell tumor of bone. Cancer, 1986,57:237-244.
[16] 孙振球主编．医学统计学(供研究生用)。北京：人民卫生出版社，2002，103-119．
[17] 王翔朴主编．卫生学．第三版．北京：人民卫生出版社，1993，289-296。
[18] Miyamoto N, Higuchi Y, Tajima M, et al. Spindle shaped cells derived from giant cell tumor of bone support differentiation of blood monocyts to osteoclastlike cells. J Orthop Res, 2000, 18: 6472654.
[19] Wulling M, Engels C, Jesse N, et al. The nature of giant cell tumor of bone. J cancer Res Clin Oncol, 2001, 127: 467-474.
[20] 刘彤华主编．诊断病理学．第1版．北京：人民卫生出版社,1994．790-807．
[21] Larsson SE, Lorentzon R,Boqudst L, et al.Giant cell tumor of bone.J Bone Joint Surg,1975,57A:167-173.
[22] Schajowicz F. Histological typing of bone tumors. Berlin: Springer Verlag, 1993. 202-222.
[23] Jiang YG, Wang YM, Li QF. Expression significance of HLA-DR antigen and heat shock protein 70 in hepatocellular carcinoma [J]. World J Gastroenterol, 2001, 9:1139-1142.
[24] Stangl K, Gunther C, Frank T, et al. Inhibition of the Ublquitln-Proteasome Path-way Induces Differential Heat-Shock Protein Response in Cardiomyocytes and Renders Early Cardiac Protection [J]. Biochem Bio- phys Res Commun, 2002, 291:542-549.
[25] Lu AL, Xu CS. Effects of heat shock on change of HSC70/HSP68, acid and alkaline phpsphatases before and after rat partial hepatectomy [J]. World J Gastroenterol, 2000, 6: 730-733.
[26] Nylandsted J,Brand K,Jaattela M.Heat shock protein 70 is required for the survival of cancer cells.Ann N Y Acad Sci,2000,926:122-125.
[27] Anderson KM,Sdvastava PK.Heat, heat shock, heat shock proteins and death: A central link in innate and adaptive immune responses, Immunol Lett,2000,74:35-39.
[28] Todryk SM, Melcher AA, Dalgleish AG, et al.Heat shock proteins refine the danger theory. Immunology,2000,99:334-337.
[29] Massa C, Guiducci C, Adoli I, et al. Enhanced efficacy of tumor cell vaccines transfected with secretable hsp70. Cancer Res,2004,64:1502-1508.
[30] Yamazaki K, Nguyen T, Podack ER.Cutting edge: Tumor secreted heat shock-fusion protein elicits CD8cells for rejection. J Immunol,1999,163:5178-5182.
[31] Melcher A, Todryk A, Hardwick N, et al.Tumor immunogenicity is determined by the mechanism of cell death via induction of heat shock protein expression. Nat Med,1998,4:581-587.
[32] Wells AD, Rai SK, Salvato MS, et al.HSP72-mediated augmentation of MHC class Ⅰ surface expression and endogenous antigen presentation. Int Immunol, 1998, 10: 609-617.
[33] PengP, MenoretA, Srivastava PK. Purifi-cation of immunogenic heat shock protein 70-peptide complexes by ADP-affinity chro-matography [J]. J Immunol Methods, 1997, 204 (1): 13-21.
[34] 张永幸，贺涵贞，邻堂春，等．职业性肺癌中热应激蛋白70，热应激蛋白27与P53表达的相关性的研究．中华劳动卫生职业病杂志，1998，16(2)：78-80．
[35] 廖文俊，叶荃，浏彦仿，等．热休克蛋白72在皮肤鳞癌中的表达．临床皮肤科杂志，1999，28(4)：225-227．
[36] 刘涛，梁传余，田聆，等．鼻咽癌HSP70和HSP90β的表达及临床意义．临床耳鼻喉科杂志．2005，19(14)：640-645．
[37] 唐伟，李家兵．HSP70和HSP90α在人膀胱癌中的表达及意义．第三军医大学学报．2005，27(6)：560-562．
[38] 董忠根，龙茂林，李贺君，等．骨巨细胞瘤的外科分期及手术类型与树后复发的关系．湖南医科大学学报．1999，24(2)：174-176．
[39] Enneking WF. A system of staging musculoskeletal neoplasma. Clin Orthop, 1986, 204:9-24.
[40] Juan Rosai．回允中译．阿克曼外科病理学．第8版．沈阳：辽宁教育出版社，1999．1957-1962．
[1] De Carcer G. Heat shock protein 90 regulates the metaphase-an-aphase transition in polo-like kinase dependent manner[J].Cancer Res.2004.64(15):5106-5112.
[2] Jiang YG, Wang YM, Li QF. Expression significance of HLA-DR antigen and heat shock protein 70 in hepatocellular carcinoma [J]. World J Gastroenterol, 2001, 9:1139-1142.
[3] Zhu X, Zhao X, Burkhold1er W F,et al. Structural analysis of substrate binding bythemolecular chaperone DnaK[J]. Science, 1996, 272(5268):1606-1614.
[4] Stangl K, Gunther C, Frank T, et al. In-hibition of the Ublquitln-Proteasome Path-way induces Differential Heat-Shock Protein Response in Cardiomyocytes and Renders Early Cardiac Protection [J]. Biochem Bio- phys Res Commun, 2002, 291: 542-549.
[5] PengP, MenoretA, Srivastava PK. Purifi-cation of immunogenic heat shock protein 70-peptide complexes by ADP-affinity chro-matography [J]. J Immunol Methods,1997, 204 (1): 13-21.
[6] Jones E L, Zhao M J,Stevenson M A, et al.The 70 kilodalton heat shock protein is an inhibitor of apoptosis in prostate cancer [J].Int J Hyperthermia. 2004. 20(8): 835-849.
[7] Wang X P,Qiu F R,Liu G Z, et al.Correlation between clinicopathology arid expression of heat shiock protein 70 and glucose-regulated protein 94 in human clinic adenocarcinoma [J].Word J Gastroenterol.2005.11(7):1056-1059.
[8] Lu AL, Xu CS. Effects of heat shock on change of HSC70/HSP68, acid arid alkaline phpsphatases before and after rat partial hepatectomy [J]. World J Gastroenterol,2000, 6: 730-733.
[9] Michils A, Redivo M, Zegers de Beyl V, et al. Increased expression Of high but not lowmolecular weight heat shock proteins in resectable lung carcinoma [J]. Lung Cancer, 2001,33(1):59-67.
[10] Hu W, Wu W, Yeung SC, et al.Increased express of heat shock protein 70 in adherent ovarian cancer and mesothelioma following treatment with manumycin a famesyl transferase inhibiyor [J].Anticancer Res,2002,22(2A):665-672.
[11] 徐先发，赵玫，施一江，等．热休克蛋白在喉癌中的表达[J]．中华耳鼻咽喉科杂志，1998，33(4)：232-234。
[12] 张永幸，贺涵贞，邻堂春，等．职业性肺癌中热应激蛋白70，热应激蛋白27 与P53表达的相关性的研究．中华劳动卫生职业病杂志，1998，16(2)：78-80．
[13] 廖文俊，叶荃，浏彦仿，等．热休克蛋白72在皮肤鳞癌中的表达．临床皮肤科杂志，1999，28(4)：225-227．
[14] Canoz O, Belenli O, Patiroglu TE.General features of gastric carcinomas and comparison of HSP70and NK cell immunoreactivity with prognostic factors. Pathol Oncol Res,2002,8:262-269.
[15] Elpek GO, Karaveli S, Simsek T, et al.Expression of heat-shock proteins hsp27, hsp70 and hsp90 in malignant epithelial tumour of the ovaries. APMIS,2003,111:523-530.
[16] Noguchi T, Takeno S, Shibata T, et al. Expression of heat shock protein70 in grossly resected esophageal squamous cell carcinoma.Ann Thorac Surg, 2002, 74:222-226.
[17] Chuma M,Sakamoto M,Yamazaki K, et al.Expression profiling in multistage hepatocarcinogenesis: identification of HSP70 as a molecular marker of early hepatocellular carcinoma.Hepatology,2003,37:198-207.
[18] Nanbu K, Konishi I,Mandai M,et al.Prognostic significance of heat shock protein HSP70 and HSP90 in endometrial carcinoma.Cancer Detect Prey, 1998, 22:549-555.
[19] Gefeller O, Jakse G, Fuzesi L. Differential expression of the heat shock protein70in the histological compartments of nephroblastomas.Anticancer Res, 2001, 21(4B):2915-2920.
[20] Nylandsted J,Rohde M, Brand K, et al.Selective depletion of heat shock protein 70 (Hsp 70) activates a tumor-specific death program that is independent of caspases and bypasses Bcl-2.Proc Natl Acad Sci USA,2000,97:7871-7876.
[21] Nylandsted J,Brand K, Jaattela M.Heat shock protein 70 is required for the survival of cancer cells.Ann N Y Acad Sci,2000,926:122-125.
[22] 赵霞，魏于全，彭芝兰．HSP70反义寡聚核苷酸诱导卵巢癌细胞凋亡．中华医学遗传学杂志，2000，17(1)：32-35．
[23] Jolly C,Morimoto RI.Role of the heat shock response and molecular chaperones in oncogenesis and cell death.J Natl Cancer Inst,2000,92(19):1564-1572.
[24] Blagosklormy M V, Toretsky J, Bohen S,et al. Mutant conformation of p53 translatedin vitroorin vivorequires functional HSP90[J]. Proc Natl Acad Sci USA, 1996, 93(16): 8379-8383.
[25] Mofified from Polla,B.S.Feige U and Polla B.S.Heat shock proteins:the Hsp70 families Experientia 1994;50:979-986.
[26] Mosser DD.Caron AW,Bourget L, et al.Role of the human heat shock prote, in hsp70 in protection against stress-induced apoptosis [J].Mol Cell Biol, 1997, 17(9):5317-5327.
[27] Chant ID,Rose PE,Morris AG.Susceptibility of AML cells to in vitro apoptosis correlates with heat shock protein70(hsp70) expression [J].Br J Haematol. 1996. 93(4):898-902.
[28] Cardoso F, Di Leo A, Larsimont D,et al. Evaluation of HER2, p53,bcl-2, topoisomerase Ⅱ-alpha, heat shock protein 27 and 70 in primary breast cancer and metastatic ipsilateral axillary lymph nodes [J]. Ann Oncol,2001,12(5):615-620.
[29] Lee YL, Corry PM. Metabolic oxidative stress-induced HSP70 geae expression is mediated through SAPK pathway [J]. J Biol Chem, 1998, 273(45): 29857-29863.
[30] Gabai VL, Meriin AB,Mcaser DD,et al.Hsp70 prevents activation of stress kinases:Anovel pathway of cellular thermotolerance [J].J Biol Chem, 1997, 272(29): 18033-18037.
[31] Blachere NE, Udono H, Janetzki S, et al.Heat shock protein vaccines against cancer [J]. J Immunother, 1993, 14 (4): 352-356.
[32] Udono H, Srivastava PK. Heat shock pro-tein 70-associated elicit specific cancer immunity [J]. J Exp Med, 1993, 178 (4):1391-1396.
[33] Blachere NE, Li Z, Chandawarkar RY, et al. Heat shock protein-peptide complexes,reconstituted in vitro, elicit peptide-specific cytotoxic T lymphocyte response and turmor immunity [J]. J Exp Med, 1997, 186(8): 1315-1322.
[34] Wells AD, Malkovsky M. Heat shock proteins, tumor immunogenicity and antigenpresentation: an integrated view [J]. Immunol Today, 2000, 21 (3): 129.
[35] Romagnani S. The Th1/Th2 Paradigm [J].Immunol Today, 1997, 18 (6): 263-266.
[36] HuangM, Wang J, Lee P, et al. Human non-small cell lung cancer cell express a type 2 cytokine pattern [J]. Cancer Res, 1995,5: 3847-3853.
[37] 傅庆国，孟凡东，郭仁宣．热休克蛋白70诱导抗肿瘤免疫的机制研究[J]．细胞与分子免疫学杂志，2002，18(4)：393-395．
[38] 黄常志，周纯。反义热休克蛋白90β对HeLa细胞恶性表型和药敏感性的影响[J]．中华肿瘤杂志，2000，22(1)：14-16．
[39] Janetzki S, Palla D, Rosenhauer V, et al.Immunization of cancer patients with autologous cancer-derived heat shock protein gp96 preparations: A pilot study [J]. Int J Cancer, 2000, 88 (2): 232-238.
[40] Multhoff G, Pfister K, Gehrmann M,et al. A 14-mer Hsp70 peptide stimulates natural killer (NK) cell activity [J]. Cell Stress Chaperones, 2001, 6(4):337-344.
[41] 傅庆国，沈晓东，孟凡东，等．热休克蛋白70与1L2抗肿瘤作用的对比研究[J]．中华肿瘤杂志，2002，24(4)：351-352．
[42] Menoret A, Chandawarkar R. Heat-shock Protein-based anticancer immunotherapy: An idea whose time has come [J]. Semin On-col, 1998, 25 (6): 654-660.
[2] Saiz P, Virkus W, Piasecki P, et al. Results of giant cell tumor of bone treated with intralesional excision. Clin Orthop, 2004, (424) :221-226.
[3] Sung HW, Kuo DP, Shu WP,et al.Giant cell tumor of bone: analysis of two hundred and eight cases in chinese patients. J Bone Joint Surg, 1982,64-A:755-761.
[4] Mcdonald DJ, Sin FH, Mcleod RA, et al.Giant cell tumor. J Bone Joint Surg, 1986,68-A:235-242.
[5] Campacci M, Baldini N, Boriani S, et al.Giant cell tumor of bone. J Bone Joint Surg, 1987,69-A:106-113.
[6] 周建伟，姜建元．骨巨细胞瘤的治疗．中华肿瘤杂志，1990，12：389-391．
[7] Schwartz HS.Update on giant cell tumor of one. ComprTher, 1998, 24(10):488-493.
[8] Koyasuu S,N is hidaE ,KadoeakiT, et al. Two mammalian heat shock proteins,HSP90 and HSP100,are actin-binding proteins. Pro Natl Acad Sci U SA, 1986, 83: 8054-8058.
[9] 曲军，祝学光，顾晋，等．HSP70mRNA在大肠癌中的高表达及其临床意义．中华实外科杂志，1998，15(6)：559-560．
[10] 徐先发，赵玫，施一江，等．热休克蛋白在喉癌中的表达．中华耳鼻喉科杂志，1998，33(4)：232-234．
[11] 李淳，程继东，蔡维佳，等．热休克蛋白70在食管鳞癌中的表达．汕头大学医学院学报，1998，11：5-6．
[12] 内藤善哉，乔炎，浅野五郎．热休克蛋白在乳腺癌中的作用．中华病理学杂志，1998．27：35-39．
[13] Sugahara K, Yamada Y, Hiragata Y,et al.Soluble and membrane isoforms of Fas/CD95 in fresh adult T-cell leukemia (ATL) cells and ATL-cell lines. Int J Cancer, 1997,72:128-132.
[14] Munker R, Midis G, Owen-Schanb L, et al.Soluble Fas (CD95) is not elevated in the serum of patients with myeloid leukemias, myeloproliferative and yelodysplastie syndromes.Leukemia, 1996,10:1531-1533.
[15] Present D, Bertoni F, Hundson T,et al.The correlation between the radiologic staging studies and histopathologic findings in aggressive stage 3 giant cell tumor of bone. Cancer, 1986,57:237-244.
[16] 孙振球主编．医学统计学(供研究生用)。北京：人民卫生出版社，2002，103-119．
[17] 王翔朴主编．卫生学．第三版．北京：人民卫生出版社，1993，289-296。
[18] Miyamoto N, Higuchi Y, Tajima M, et al. Spindle shaped cells derived from giant cell tumor of bone support differentiation of blood monocyts to osteoclastlike cells. J Orthop Res, 2000, 18: 6472654.
[19] Wulling M, Engels C, Jesse N, et al. The nature of giant cell tumor of bone. J cancer Res Clin Oncol, 2001, 127: 467-474.
[20] 刘彤华主编．诊断病理学．第1版．北京：人民卫生出版社,1994．790-807．
[21] Larsson SE, Lorentzon R,Boqudst L, et al.Giant cell tumor of bone.J Bone Joint Surg,1975,57A:167-173.
[22] Schajowicz F. Histological typing of bone tumors. Berlin: Springer Verlag, 1993. 202-222.
[23] Jiang YG, Wang YM, Li QF. Expression significance of HLA-DR antigen and heat shock protein 70 in hepatocellular carcinoma [J]. World J Gastroenterol, 2001, 9:1139-1142.
[24] Stangl K, Gunther C, Frank T, et al. Inhibition of the Ublquitln-Proteasome Path-way Induces Differential Heat-Shock Protein Response in Cardiomyocytes and Renders Early Cardiac Protection [J]. Biochem Bio- phys Res Commun, 2002, 291:542-549.
[25] Lu AL, Xu CS. Effects of heat shock on change of HSC70/HSP68, acid and alkaline phpsphatases before and after rat partial hepatectomy [J]. World J Gastroenterol, 2000, 6: 730-733.
[26] Nylandsted J,Brand K,Jaattela M.Heat shock protein 70 is required for the survival of cancer cells.Ann N Y Acad Sci,2000,926:122-125.
[27] Anderson KM,Sdvastava PK.Heat, heat shock, heat shock proteins and death: A central link in innate and adaptive immune responses, Immunol Lett,2000,74:35-39.
[28] Todryk SM, Melcher AA, Dalgleish AG, et al.Heat shock proteins refine the danger theory. Immunology,2000,99:334-337.
[29] Massa C, Guiducci C, Adoli I, et al. Enhanced efficacy of tumor cell vaccines transfected with secretable hsp70. Cancer Res,2004,64:1502-1508.
[30] Yamazaki K, Nguyen T, Podack ER.Cutting edge: Tumor secreted heat shock-fusion protein elicits CD8cells for rejection. J Immunol,1999,163:5178-5182.
[31] Melcher A, Todryk A, Hardwick N, et al.Tumor immunogenicity is determined by the mechanism of cell death via induction of heat shock protein expression. Nat Med,1998,4:581-587.
[32] Wells AD, Rai SK, Salvato MS, et al.HSP72-mediated augmentation of MHC class Ⅰ surface expression and endogenous antigen presentation. Int Immunol, 1998, 10: 609-617.
[33] PengP, MenoretA, Srivastava PK. Purifi-cation of immunogenic heat shock protein 70-peptide complexes by ADP-affinity chro-matography [J]. J Immunol Methods, 1997, 204 (1): 13-21.
[34] 张永幸，贺涵贞，邻堂春，等．职业性肺癌中热应激蛋白70，热应激蛋白27与P53表达的相关性的研究．中华劳动卫生职业病杂志，1998，16(2)：78-80．
[35] 廖文俊，叶荃，浏彦仿，等．热休克蛋白72在皮肤鳞癌中的表达．临床皮肤科杂志，1999，28(4)：225-227．
[36] 刘涛，梁传余，田聆，等．鼻咽癌HSP70和HSP90β的表达及临床意义．临床耳鼻喉科杂志．2005，19(14)：640-645．
[37] 唐伟，李家兵．HSP70和HSP90α在人膀胱癌中的表达及意义．第三军医大学学报．2005，27(6)：560-562．
[38] 董忠根，龙茂林，李贺君，等．骨巨细胞瘤的外科分期及手术类型与树后复发的关系．湖南医科大学学报．1999，24(2)：174-176．
[39] Enneking WF. A system of staging musculoskeletal neoplasma. Clin Orthop, 1986, 204:9-24.
[40] Juan Rosai．回允中译．阿克曼外科病理学．第8版．沈阳：辽宁教育出版社，1999．1957-1962．
[1] De Carcer G. Heat shock protein 90 regulates the metaphase-an-aphase transition in polo-like kinase dependent manner[J].Cancer Res.2004.64(15):5106-5112.
[2] Jiang YG, Wang YM, Li QF. Expression significance of HLA-DR antigen and heat shock protein 70 in hepatocellular carcinoma [J]. World J Gastroenterol, 2001, 9:1139-1142.
[3] Zhu X, Zhao X, Burkhold1er W F,et al. Structural analysis of substrate binding bythemolecular chaperone DnaK[J]. Science, 1996, 272(5268):1606-1614.
[4] Stangl K, Gunther C, Frank T, et al. In-hibition of the Ublquitln-Proteasome Path-way induces Differential Heat-Shock Protein Response in Cardiomyocytes and Renders Early Cardiac Protection [J]. Biochem Bio- phys Res Commun, 2002, 291: 542-549.
[5] PengP, MenoretA, Srivastava PK. Purifi-cation of immunogenic heat shock protein 70-peptide complexes by ADP-affinity chro-matography [J]. J Immunol Methods,1997, 204 (1): 13-21.
[6] Jones E L, Zhao M J,Stevenson M A, et al.The 70 kilodalton heat shock protein is an inhibitor of apoptosis in prostate cancer [J].Int J Hyperthermia. 2004. 20(8): 835-849.
[7] Wang X P,Qiu F R,Liu G Z, et al.Correlation between clinicopathology arid expression of heat shiock protein 70 and glucose-regulated protein 94 in human clinic adenocarcinoma [J].Word J Gastroenterol.2005.11(7):1056-1059.
[8] Lu AL, Xu CS. Effects of heat shock on change of HSC70/HSP68, acid arid alkaline phpsphatases before and after rat partial hepatectomy [J]. World J Gastroenterol,2000, 6: 730-733.
[9] Michils A, Redivo M, Zegers de Beyl V, et al. Increased expression Of high but not lowmolecular weight heat shock proteins in resectable lung carcinoma [J]. Lung Cancer, 2001,33(1):59-67.
[10] Hu W, Wu W, Yeung SC, et al.Increased express of heat shock protein 70 in adherent ovarian cancer and mesothelioma following treatment with manumycin a famesyl transferase inhibiyor [J].Anticancer Res,2002,22(2A):665-672.
[11] 徐先发，赵玫，施一江，等．热休克蛋白在喉癌中的表达[J]．中华耳鼻咽喉科杂志，1998，33(4)：232-234。
[12] 张永幸，贺涵贞，邻堂春，等．职业性肺癌中热应激蛋白70，热应激蛋白27 与P53表达的相关性的研究．中华劳动卫生职业病杂志，1998，16(2)：78-80．
[13] 廖文俊，叶荃，浏彦仿，等．热休克蛋白72在皮肤鳞癌中的表达．临床皮肤科杂志，1999，28(4)：225-227．
[14] Canoz O, Belenli O, Patiroglu TE.General features of gastric carcinomas and comparison of HSP70and NK cell immunoreactivity with prognostic factors. Pathol Oncol Res,2002,8:262-269.
[15] Elpek GO, Karaveli S, Simsek T, et al.Expression of heat-shock proteins hsp27, hsp70 and hsp90 in malignant epithelial tumour of the ovaries. APMIS,2003,111:523-530.
[16] Noguchi T, Takeno S, Shibata T, et al. Expression of heat shock protein70 in grossly resected esophageal squamous cell carcinoma.Ann Thorac Surg, 2002, 74:222-226.
[17] Chuma M,Sakamoto M,Yamazaki K, et al.Expression profiling in multistage hepatocarcinogenesis: identification of HSP70 as a molecular marker of early hepatocellular carcinoma.Hepatology,2003,37:198-207.
[18] Nanbu K, Konishi I,Mandai M,et al.Prognostic significance of heat shock protein HSP70 and HSP90 in endometrial carcinoma.Cancer Detect Prey, 1998, 22:549-555.
[19] Gefeller O, Jakse G, Fuzesi L. Differential expression of the heat shock protein70in the histological compartments of nephroblastomas.Anticancer Res, 2001, 21(4B):2915-2920.
[20] Nylandsted J,Rohde M, Brand K, et al.Selective depletion of heat shock protein 70 (Hsp 70) activates a tumor-specific death program that is independent of caspases and bypasses Bcl-2.Proc Natl Acad Sci USA,2000,97:7871-7876.
[21] Nylandsted J,Brand K, Jaattela M.Heat shock protein 70 is required for the survival of cancer cells.Ann N Y Acad Sci,2000,926:122-125.
[22] 赵霞，魏于全，彭芝兰．HSP70反义寡聚核苷酸诱导卵巢癌细胞凋亡．中华医学遗传学杂志，2000，17(1)：32-35．
[23] Jolly C,Morimoto RI.Role of the heat shock response and molecular chaperones in oncogenesis and cell death.J Natl Cancer Inst,2000,92(19):1564-1572.
[24] Blagosklormy M V, Toretsky J, Bohen S,et al. Mutant conformation of p53 translatedin vitroorin vivorequires functional HSP90[J]. Proc Natl Acad Sci USA, 1996, 93(16): 8379-8383.
[25] Mofified from Polla,B.S.Feige U and Polla B.S.Heat shock proteins:the Hsp70 families Experientia 1994;50:979-986.
[26] Mosser DD.Caron AW,Bourget L, et al.Role of the human heat shock prote, in hsp70 in protection against stress-induced apoptosis [J].Mol Cell Biol, 1997, 17(9):5317-5327.
[27] Chant ID,Rose PE,Morris AG.Susceptibility of AML cells to in vitro apoptosis correlates with heat shock protein70(hsp70) expression [J].Br J Haematol. 1996. 93(4):898-902.
[28] Cardoso F, Di Leo A, Larsimont D,et al. Evaluation of HER2, p53,bcl-2, topoisomerase Ⅱ-alpha, heat shock protein 27 and 70 in primary breast cancer and metastatic ipsilateral axillary lymph nodes [J]. Ann Oncol,2001,12(5):615-620.
[29] Lee YL, Corry PM. Metabolic oxidative stress-induced HSP70 geae expression is mediated through SAPK pathway [J]. J Biol Chem, 1998, 273(45): 29857-29863.
[30] Gabai VL, Meriin AB,Mcaser DD,et al.Hsp70 prevents activation of stress kinases:Anovel pathway of cellular thermotolerance [J].J Biol Chem, 1997, 272(29): 18033-18037.
[31] Blachere NE, Udono H, Janetzki S, et al.Heat shock protein vaccines against cancer [J]. J Immunother, 1993, 14 (4): 352-356.
[32] Udono H, Srivastava PK. Heat shock pro-tein 70-associated elicit specific cancer immunity [J]. J Exp Med, 1993, 178 (4):1391-1396.
[33] Blachere NE, Li Z, Chandawarkar RY, et al. Heat shock protein-peptide complexes,reconstituted in vitro, elicit peptide-specific cytotoxic T lymphocyte response and turmor immunity [J]. J Exp Med, 1997, 186(8): 1315-1322.
[34] Wells AD, Malkovsky M. Heat shock proteins, tumor immunogenicity and antigenpresentation: an integrated view [J]. Immunol Today, 2000, 21 (3): 129.
[35] Romagnani S. The Th1/Th2 Paradigm [J].Immunol Today, 1997, 18 (6): 263-266.
[36] HuangM, Wang J, Lee P, et al. Human non-small cell lung cancer cell express a type 2 cytokine pattern [J]. Cancer Res, 1995,5: 3847-3853.
[37] 傅庆国，孟凡东，郭仁宣．热休克蛋白70诱导抗肿瘤免疫的机制研究[J]．细胞与分子免疫学杂志，2002，18(4)：393-395．
[38] 黄常志，周纯。反义热休克蛋白90β对HeLa细胞恶性表型和药敏感性的影响[J]．中华肿瘤杂志，2000，22(1)：14-16．
[39] Janetzki S, Palla D, Rosenhauer V, et al.Immunization of cancer patients with autologous cancer-derived heat shock protein gp96 preparations: A pilot study [J]. Int J Cancer, 2000, 88 (2): 232-238.
[40] Multhoff G, Pfister K, Gehrmann M,et al. A 14-mer Hsp70 peptide stimulates natural killer (NK) cell activity [J]. Cell Stress Chaperones, 2001, 6(4):337-344.
[41] 傅庆国，沈晓东，孟凡东，等．热休克蛋白70与1L2抗肿瘤作用的对比研究[J]．中华肿瘤杂志，2002，24(4)：351-352．
[42] Menoret A, Chandawarkar R. Heat-shock Protein-based anticancer immunotherapy: An idea whose time has come [J]. Semin On-col, 1998, 25 (6): 654-660.