Prognostic and immunological roles of heat shock protein A4 in lung adenocarcinoma

BACKGROUND Heat shock protein A4(HSPA4)belongs to molecular chaperone protein family which plays important roles within variable cellular activities,including cancer initiation and progression.However,the prognostic and immunological significance of HSPA4 in lung adenocarcinoma(LUAD)has not been revealed yet.AIM To explore the prognostic and immunological roles of HSPA4 to identify a novel prognostic biomarker and therapeutic target for LUAD.METHODS We assessed the prognostic and immunological significance of HSPA4 in LUAD using data from The Cancer Genome Atlas database.The association between HSPA4 expression and clinical-pathological features was assessed through Kruskal-Wallis and Wilcoxon signed-rank test.Univariate/multivariate Cox regression analyses and Kaplan-Meier curves were employed to evaluate prognostic factors,including HSPA4,in LUAD.Gene set enrichment analysis(GSEA)was conducted to identify the key signaling pathways associated with HSPA4.The correlation between HSPA4 expression and cancer immune infiltration was evaluated using single-sample gene set enrichment analysis(ssGSEA).RESULTS Overexpressing HSPA4 was significantly related to advanced pathologic TNM stage,advanced pathologic stage,progression disease status of primary therapy outcome and female subgroups with LUAD.In addition,increased HSPA4 expression was found to be related to worse disease-specific survival and overall survival.GSEA analysis indicated a significant correlation between HSPA4 and cell cycle regulation and immune response,particularly through diminishing the function of cytotoxicity cells and CD8 T cells.The ssGSEA algorithm showed a positive correlation between HSPA4 expression and infiltrating levels of Th2 cells,while a negative correlation was observed with cytotoxic cell infiltration levels.CONCLUSION Our findings indicate HSPA4 is related to prognosis and immune cell infiltrates and may act as a novel prognostic biomarker and therapeutic target for LUAD.

Different Responses of Camptothecin and 10-Hydroxycamptothecin to Heat Shock in Camptotheca acuminata Seedlings

Plants interact with their environment by producing a diverse array of secondary metabolites, one of which is alkaloid. In this study, alkaloids, including camptothecin (CPT) and 10-hydroxycamptothecin (HCPT), malondialdehyde (MDA) and chlorophyll contents were measured during heat shock in seedlings of Camptotheca acuminata Decaisne unique to China. Responses of different tissues, including young leaves, old leaves, buds and barks, to heat shock were examined in alkaloid changes. CPT and HCPT concentrations reached their peak values separately at 38 degreesC and 40 degreesC, which were below the lethal heat-shock temperature indicated by MDA and chlorophyll, and their great changes took place in young leaves. These results indicated that CPT and HCPT were involved in the C acuminata resistance against heat shock from its environment. Furthermore, plant rigidly observed the cost-benefit principle and mobilized and allocated limited alkaloid sources to young and reproductive tissues preferentially. In addition, HCPT displayed well-regulated changes during incubation at sublethal temperature, and this indicated that HCPT might play a more positively defensive role in enhancement of plant thermotolerance than CPT does.

Molecular Cloning the Gene of Small Heat Shock Protein in the Mitochondria and Endoplasmic Reticulum of Tomato

A cDNA Library was constructed with the heat shocked tomato ( Lycopersicon esculentum Mill.) flowers and then was screened with the probes of mitochondrial and endoplasmic reticulum conservative regions that were cloned by using RT-PCR. The complete cDNAs of mitochondrial and endoplasmic reticulum small heat shock protein ( shsp) were selected out from the cDNA library. Furthermore, the temperature responses of these shsp genes were determined. Northern hybridization showed that the heat response temperatures of both genes in tomato flower were lower than that in leaf and that mitochondria shsp in leaf was cold-inducible. In this paper, the molecular features of the cloned genes, the causes of the uncommon heat response temperatures of sHSP in newer and the cold inducible character of mitochondria shsp gene in leaf were discussed.

Regulation of Heat Shock Factor AtHsfA1a on Ascorbate Peroxidase under Heat Stress in Arabidopsis thaliana

[Objective] This study was conducted to investigate the regulation of heat shock factor AtHsfA1a on ascorbate peroxidase under heat stress in Arabidopsis thaliana. [Method] After heat stress treatment on transgenetic A. thaliana with silenced endogenetic AtHsfA1a gene and wild A. thaliana plants as materials, the change in activity of APX enzyme was analyzed by spectrophotometry, the expression level of APX gene was investigated by real-time fluorescent quantitative PCR, and the binding condition of AtHsfAla with the promoter region of APX gene was analyzed by chromatin immunoprecipitation assay. [Result] The activity and mRNA level of APX in plants with silenced endogenetic AtHsfAla gene were higher than those in wild plants. Fragments of the promoter region of APX gene were not screened from the plants with silenced endogenetic AtHsfA1a gene, but found in wild plants. [Conclusion] This study provides a theoretical basis for the understanding of the important role of AtHsfAla in resistance to stress in plant, and is of great significance to the revealing of mechanism of resistance to stress in plant.

Heat Shock Proteins Inducement in Wheat Seedling

High temperature is an important limiting factor to the improvement of wheat yield. When suffered hot stress,wheat will produce a series of heat shock proteins to adapt this adversity. In different upgrowth phases,or different heat-resistant crop varieties,the heat shock protein exist differences. Therefore,study on differences of heat shock protein has significant theoretical and practical meaning for researching heat resistance of wheat. By using SDS-PAGE method,the inducing conditions and manifestation of heat shock protein were studied,which provided theoretical basis for yield increasing of wheat.

Prokaryotic Expression and Purification of Heat Shock Factor HSF1 in Arabidopsis thaliana

[ Objective ] This study was to express and purify Arabidopsis thaliana heat shock factor HSF1. [ Method ] Using Escherichia coli M15 harboring HSF1 （pQE32/His6-HSF1, pREP4） as experimental materials, HSF1 was induced to express with isopropyl-β-D-galactoside （IPTG） ; then the expression product was purified using Ni-NTA-agarose affinity chromatography and analyzed by SDS-PAGE. [Result] HSF1 of Arabidopsis thaliana was successfully expressed and purified. [ Conclusion] This study provides materials for understanding the blinding site of HSF1 on Arabidopsis thaliana chromosome, further laying a good foundation for revealing the regulatory mechanism and physiological function of HSF1.

Expression of heat shock proteins (HSP27, HSP60, HSP70, HSP90, GRP78, GRP94) in hepatitis B virus-related hepatocellular carcinomas and dysplastic nodules

AIM: Expression of heat shock proteins (HSPs) is frequently up-regulated in hepatocellular carcinoma (HCC), which evolves from dysplastic nodule (DN) and early HCC to advanced HCC. However, little is known about the differential expression of HSPs in multistep hepatocarcinogenesis. It was the purpose of this study to monitor the expression of HSPs in multistep hepatocarcinogenesis and to evaluate their prognostic significance in hepatitis B virus (HBV)related HCC.METHODS: Thirty-eight HCC and 19 DN samples were obtained from 52 hepatitis B surface antigen-positive Korean patients. Immunohistochemical and dot immunoblot analyses of HSP27, HSP60, HSP70, HSP90, glucoseregulated protein (GRP)78, and GRP94 were performed and their expression at different stages of HCC development was statistically analyzed.RESULTS: Expression of HSP27, HSP70, HSP90, GRP78, and GRP94 increased along with the stepwise progression of hepatocarcinogenesis. Strong correlation was found only in GRP78 (Spearman's r= 0.802). There was a positive correlation between the expressions of GRP78, GRP94, HSP90, or HSP70 and prognostic factors of HCC. Specifically, the expression of GRP78, GRP94, or HSP90 was associated significantly with vascular invasion and intrahepatic metastasis.CONCLUSION: The expressions of HSPs are commonly up-regulated in HBV-related HCCs and GRP78 might play an important role in the stepwise progression of HBVrelated hepatocarcinogenesis. GRP78, GRP94, and HSP90 may be important prognostic markers of HBV-related HCC, strongly suggesting vascular invasion and intrahepatic metastasis.

Heat-shocked tumor cell lysate-pulsed dendritic cells induce effective anti-tumor immune response in vivo

AIM. To study whether heat-shocked tumor cells could enhance the effect of tumor cell lysate-pulsed dendritic cells （DCs） in evoking anti-tumor immune response in vivo. METHODS： Mouse undifferentiated colon cancer cells （CT-26） were heated at 42℃ for 1 h and then frozenthawed. The bone marrow-derived DCs pulsed with heatshocked CT-26 cell lysate （HSCT-26 DCs） were recruited to immunize syngeneic naive BALB/c mice. The cytotoxic activity of tumor specific cytotoxic T lymphocytes （CTLs） in mouse spleen was evaluated by IFN-enzyme-linked immunospot （ELISpot） and LDH release assay. The immunoprophylactic effects induced by HSCT-26 DCs in mouse colon cancer model were compared to those induced by single CT-26 cell lysate-pulsed DCs （CT-26 DCs） on tumor volume, peritoneal metastasis and survival time of the mice. RESULTS： Heat-treated CT-26 cells showed a higher hsp70 protein expression. Heat-shocked CT-26 cell lysate pulsing elevated the co-stimulatory and MHC-Ⅱ molecule expression of bone marrow-derived DCs as well as interleukin-12 p70 secretion. The IFN-y secreting CTLs induced by HSCT-26 DCs were significantly more than those induced by CT-26 DCs （P=0.002）. The former CTLs＇ specific cytotoxic activity was higher than the latter CTLs＇ at a serial E/T ratio of 10：1, 20：1, and 40：1. Mouse colon cancer model showed that the tumor volume of HSCT-26 DC vaccination group was smaller than that of CT-26 DC vaccination group on tumor volume though there was no statistical difference between them （24 mm^3 vs 8 mm^3, P=0.480）. The median survival time of mice immunized with HSCT-26 DCs was longer than that of those immunized with CT-26 DCs （57 d vs 43 d, P = 0.0384）. CONCLUSION： Heat-shocked tumor cell lysate-pulsed DCs can evoke anti-tumor immune response in vivo effectively and serve as a novel DC-based tumor vaccine.

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.

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 clinicopathology 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% vs56.3%, 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% vs 75%, 100% CONCLUSION: The HSP70 and grp94 expression rates in colonic cancer groups are significantly higher than that in their adjacent mucous membrane. The HSP70 and grp94 expression in poorly-differentiated colonic cancers with metastasis is significantly higher than well-differentiated cancers without metastasis. The overexpression of HSP70 and grp94 can be used as diagnostic or prognostic markers for colonic cancer.

H pylori infection and systemic antibodies to CagA and heat shock protein 60 in patients with coronary heart disease

AIM: To determine the overall prevalence of H pylori and CagA positive H pylori infection and the prevalence of other bacterial and viral causes of chronic infection in patients with coronary heart disease (CHD), and the potential role of anti-heat-shock protein 60 (Hsp60) anti- body response to these proteins in increasing the risk of CHD development. METHODS: Eighty patients with CHD and 160 controls were employed. We also compared the levels of anti- heat-shock protein 60 (Hsp60) antibodies in the two groups. The H pylori infection and the CagA status were determined serologically, using commercially available enzyme-linked immunosorbent assays (ELISA), and a Western blotting method developed in our laboratory. Systemic antibodies to Hsp60 were determined by a sandwich ELISA, using a polyclonal antibody to Hsp60 to sensitise polystyrene plates and a commercially available human Hsp60 as an antigen. RESULTS: The overall prevalence of H pylori infec- tion was 78.7% (n = 63) in patients and 76.2% (n = 122) in controls (P = 0.07). Patients infected by CagA- positive (CagA+) H pylori strains were 71.4% (n = 45) vs 52.4% of infected controls (P = 0.030, OR = 2.27). Sys-temic levels of IgG to Hsp60 were increased in H pylori- negative patients compared with uninfected controls (P < 0.001) and CagA-positive infected patients compared with CagA-positive infected controls (P = 0.007). CONCLUSION: CagA positive H pylori infection may concur to the development of CHD; high levels of anti- Hsp60 antibodies may constitute a marker and/or a con- comitant pathogenic factor of the disease.

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.

Association of high expression in rat gastric mucosal heat shock protein 70 induced by moxibustion pretreatment with protection against stress injury

AIM:To study the effect of moxibustion on Zusanli or Liangmeng point on gastric mucosa injury in stress-induced ulcer rats and its correlation with the expression of heat shock protein 70 (HSP70). METHODS:Sixty healthy SD rats (30 males,30 females) were divided into control group,injury model group,Zushanli point group,Liangmeng point group. Stress gastric ulcer model was induced by binding cold stress method. Gastric mucosa ulcer injury (UI) index was calculated by Guth method. Gastric mucosa blood flow (GMBF) was recorded with a biological signal analyzer. Protein content and gene expression in gastric mucosal HSP70 were detected by immunohistochemistry (IHC) and reverse transcription polymerase chain reaction (RT-PCR). Thiobarbital method was used to determine malondialdehyde (MDA) content. Gastric mucosal endothelin (ET) and prostaglandin E2 (PGE2) were analyzed by radioimmunoassay. RESULTS:High gastric mucosal UI index,high HSP70 expression,low GMBF and PGF2,elevated MDA and ET were observed in gastric mucosa of rats subjected to cold stress. Moxibustion on Zusanli or Liangmeng point decreased rat gastric mucosal UI index,MDA and ET. Conversely,the expression of HSP70,GMBF,and PGE2 was elevated in gastric mucosa after pretreatment with moxibustion on Zusanli or Liangmeng point. The observed parameters were significantly different between Zusanli and Liangmeng points. CONCLUSION:Pretreatment with moxibustion on Zusanli or Liangmeng point protects gastric mucosa against stress injury. This protection is associated with the higher expression of HSP70 mRNA and protein,leading to release of PGE2 and inhibition of MDA and ET,impairment of gastric mucosal index.

Primary evidence for involvement of IP_(3) in heat-shock signal transduction in Arabidopsis

The role of inositol 1,4,5-trisphosphate （IP3） in transducing heat-shock （HS） signals was examined in Arabidopsis. The whole-plant IP3 level increased within 1 min of HS at 37℃. After 3 min of HS, the IP3 level reached a maximum 2.5 fold increase. Using the transgenic Arabidopsis plants that have AtHsp 18.2 promoter-β-glucuronidase （GUS） fusion gene, it was found that the level of GUS activity was up-regulated by the addition of caged IP3 at both non-HS and HS temperatures and was down-regulated by the phospholipase C （PLC） inhibitors {1-[6-（（ 1713-3-Methoxyestra-1,3,5（10）-trien- 7-yl）amino）hexyl]-2,5-pyrrolidinedione } （U-73122）. The intracellular-free calcium ion concentration （[Ca^2＋]i） increased during HS at 37℃ in suspension-cultured Arabidopsis cells expressing apoaequorin. Treatment with U-73122 prevented the increase of [Ca^2＋]i to some extent. Above results provided primary evidence for the possible involvement of IP3 in HS signal transduction in higher plants.

The mRNA Expression Profiles of Five Heat Shock Protein Genes from Frankliniella occidentalis at Different Stages and Their Responses to Temperatures and Insecticides

The westem flower thrips, Frankliniella occidental＆ （Pergande） is a highly invasive pest that is able to exploit many crops across a wide range of environmental conditions. Five full-length cDNAs of heat shock protein （HSP） genes （Fo-HSP90, Fo-HSP70, Fo-HSP60, Fo-HSP40 and Fo-HSP28.9） were cloned from F. occidentalis, and their expression profiles were investigated under conditions of thermal stress and insecticide exposure, and at different stages during development, using real-time quantitative PCR. All five gene sequences showed high similarity to homologs in other species, indicating the conserved fimction of this gene family. HSP60 represents an informative phylogenetic marker at the ordinal taxonomic level within Insecta, but HSP90, which has two homologous copies in Hymenoptera, was not informative. The expression of Fo-HSPs under thermal stress suggests that Fo-HSP90, Fo-HSP70, and Fo-HSP28.9 are inducible by both cold and heat stress, Fo-HSP40 is only heat-inducible, and Fo-HSP60 is thermally insensitive. There were two patterns of cold induction of Fo-HSPs： one is from 0 to 4℃ and the other is around -8℃. All five Fo-HSPs genes were induced by exposure to sublethal concentrations of the insecticide avermectin. The expression of the five Fo-HSPs during different developmental stages suggests that they all play a role in development of F. occidentalis.

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.

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.

Advance in Research on Biological Function and TranscriptionalControl of Heat Shock Proteins

The regulation of heat shock transcription factor to heat shock protein expression and the newest knowledge about the effect of heat shock protein on aging,immune response and the balance of cell survival and apoptosis are summarized in the paper.

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.

Recent advances in heat shock protein-based cancer vaccines

BACKGROUND: Active immunotherapy has been successful in preventing many infectious diseases, and is being explored for its anti-tumor use. Purified antigens, peptides, gene-based systems and antigens contained in whole cells or cell lysates are used in specific active immunotherapy for cancer, known as cancer vaccines. Cancer vaccines do not directly kill tumor cells, but prime a specific humoral and/or cellular immune response against the tumor. Up to date, many kinds of cancer vaccines have been tested in the world and have shown their own advantages. Heat shock protein (HSP)-based cancer vaccine is one of the outstanding representatives. In this paper, we review recent advances in HSP-based cancer vaccines. DATA SOURCES: An English-language literature search was conducted using MEDLINE (1990-2005) on HSP, cancer vaccines and other related subjects. RESULTS: Several kinds of HSP-based cancer vaccines which have been explored worldwide, include tumor derived HSP-pepdde complex cancer vaccines, artificially reconstituted HSP-peptide complex cancer vaccines, HSPpeptide fusion protein cancer vaccines and HSP-based DNA cancer vaccines, etc. Many HSP-based cancer vaccines are being tested in clinical trials, and some are being tested in phase Ⅲ clinical trials at present. CONCLUSION: The available results in preclinical tests and clinical trials indicate that HSP-based cancer vaccines are promising in cancer therapy.