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.

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.

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.

Novel heat shock protein Hsp70L1 activates dendritic cells and acts as a Th1 polarizing adjuvant

Heat shock proteins (HSPs) are reported to act as effective adjuvants to elicit anti-tumor and anti-infection immunity. Here, we report that Hsp70-like protein 1 (Hsp70L1), a novel HSP derived from human dendritic cells (DCs), has potent adjuvant effects that polarize responses toward Th1. With a calculated molecular weight of 54.8 kDa, Hsp70L1 is smaller in size than Hsp70 but resembles it both structurally and functionally. Hsp70L1 shares common receptors on DCs with Hsp70 and can interact with DCs, promoting DC maturation and stimulating secretion of the proinflammatory cytokines interleukin 12p70 (IL-12p70), IL-1beta, tumor necrosis factor-alpha (TNF-alpha), and the chemokines IP-10, macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, and normal T cell expressed and secreted (RANTES). The induction of interferon-gamma-inducible protein 10 (IP-10) secretion by Hsp70L1 is not shared by Hsp70, and other functional differences include more potent stimulation of DC IL-12p70, CC-chemokine, and CCR7 and CXCR4 expression by Hsp70L1. Immunization of mice with the hybrid peptide Hsp70L1-ovalbumin(OVA)(257-264) induces an OVA(257-264)-specific Th1 response and cytotoxic T lymphocyte (CTL) that results in significant inhibition of E.G7-OVA tumor growth. The ability of Hsp70L1 to activate DCs indicates its potential as a novel adjuvant for use with peptide immunizations; the Hsp70L1 antigen peptide hybrid may serve as a more effective vaccine for the control of cancer and infectious diseases.

EXPERIMENTAL STUDY ON MOXIBUSTION AT ZUSANLI(ST 36) AND LIANGMEN (ST 21) INDUCING HEAT SHOCK PROTEIN 70 (HSP70) EXPRESSION TO RESIST OXIDATIVE INJURY OF GASTRIC MUCOSA

To observe effect of moxibustion at Zusanli （足三里 ST 36） and Liangmen （梁门 ST 21 ） on expression of heat shock protein 70 （HSP70） in gastric mucosa of the rat of stress ulcer （SU） to explore the mechanism of moxibustion in resisting oxidative injury of the gastric mucosa. Methods： Sixty SD rats were evenly randomized into 4 groups, a blank group, a model group, an acupoint moxibustion group and a non-acupoint moxibustion group. Water restraint stress （WRS） method was used to make stress gastric ulcer rat model. The ulcerative index （Ul） of gastric mucosa was evaluated by using GUTH method, the gastric mu- cosa blood flux （GMBF） was detected by a laser Doppler bloodflow monitor, and HSP70 expression and malondialdehyde （MDA） content in the gastric mucosa were determined respectively with immunohistochemical and thiobarbiturate methods. Results： Moxibustion at Zusanli （ST 36） and Liangmen （ST 21 ） significantly de- creased Ul, up-regulated HSP70 expression, increased GMBF, and decreased MDA content in the gastric mucosa in the rat of stress gastric ulcer, with significant differences as compared with the model group and the non-acupoint moxibustion group （P 〈 0.05 or P 〈 0.01 ）. Conclusion： Moxibustion at Zusanli （ST 36） and Liangmen （ST 21 ） can induce high expression of HSP70 and decrease MDA content in the gastric mucosa, so as to resist oxidative injury, with relative acupoint specificity.

Study of Heat Shock Protein HSP90α，HSP70，HSP27 mRNA Expression in Human Acute Leukemia Cells

The expression of three heat shock proteins (HSPs)-HSP90, HSP70,HSP27 in cells obtained from 22 patients with leukemia, K562 erythroleukemia cell line, and normal blood cells was observed by means of RNA dot blot analysis.The results showed that the expression of the HSP27 gene was enhanced in 4 cases of acute lymphoid leukemia (ALL), 7 cases of acute nonlymphoid leukemia (ANLL) and 2 cases of myelodysplastic syndrome (MDS) as compared with that of the normal blood cells, yet there was no significant difference in the HSP27 expression between the ALL and ANLL cells. The expression of HSP70 in all the 5 ALL and ANLL patients was much lower than that of the normal subjects, except 1 case of ALL and 1 case of MDS, in which the expression was obviously enhanced. All the cases including 11 ANLL, 5 ALL and 1 MDS had higher HSP90α expression than the normal subjects. The enhanced expression of HSP90α in leukemia cells may be associated with the active and indefinite proliferation of leukemia cells. Our results also suggest that the high expression of the HSP27gene may not be confined to a specific type of acute leukemia.

Cloning and Expression Analysis of Heat Shock Protein Gene DpHsp70 in Dahlia

[Objectives]This study was conducted to investigate the relationship between HSPs and the response of high temperature stress.[Methods]Molecular biological techniques were applied to clone and analyze the gene sequence of DpHsp70 gene.The changes in the expression of DpHsp70 gene under high temperature stress and exogenous salicylic acid(SA)were observed and further analyzed by qRT PCR.[Results]The coding region of the Dahlia DpHsp70 gene was 705 bp,encoding 234 amino acid residues(GenBank accession number:MH102288).Aligned with Compositae plants,the Dahlia DpHsp70 gene shared more than 83%homology in gene sequence while 99%-100%homology in amino acid sequence.Under the 35℃high temperature stress,the expression of DpHsp70 gene in Dahlia petals significantly increased.Meanwhile,the expression of DpHsp70 gene further increased under SA at 35℃temperature,which was significantly higher than those of the control group and the 35℃high temperature stress treatment group.It was demonstrated that the Hsp70 gene in Compositae is with highly conservative property and its expression could be up-regulated in response to high temperature stress.It can also be concluded that applying exogenous SA can improve the high temperature resistance of Dahlia.[Conclusions]This study provides a new experimental basis for elucidating the physiological function and mechanism of Dahlia in response to high temperature stress.

cDNA Cloning of Heat Shock Protein Genes and Their Expression in an Indigenous Cryptic Species of the Whitefly Bemisia tabaci Complex from China

Thermal adaptation plays a fundamental role in shaping the distribution and abundance of insects,and heat shock proteins（Hsps）play important roles in the temperature adaptation of various organisms.To better understand the temperature tolerance of the indigenous ZHJ2-biotype of whitefly Bemisia tabaci species complex,we obtained complete cDNA sequences for hsp90,hsp70,and hsp20 and analyzed their expression profiles under different high temperature treatments by real-time quantitative polymerase chain reaction.The high temperature tolerance of B.tabaci ZHJ2-biotype was determined by survival rate after exposure to different high temperatures for 1 h.The results showed that after 41°C heat-shock treatment for 1 h,the survival rates of ZHJ2 adults declined significantly and the estimated temperature required to cause 50% mortality（LT50）is 42.85°C for 1 h.Temperatures for onset（Ton）or maximal（Tmax）induction of hsps expression in B.tabaci ZHJ2-biotype were 35 and 39°C（or 41°C）.Compared with previous studies,indigenous ZHJ2-biotype exhibits lower heat temperature stress tolerance and Ton（or Tmax）than the invasive B-biotype.

Heat shock protein inhibitor, quercetin, as a novel adjuvant agent to improve radiofrequency ablation-induced tumor destruction and its molecular mechanism

Background： We investigated the effect of a small molecular inhibitor of heat shock protein （HSP）, qnercetin, on tumor radiofrequency （RF） ablation, and explored the underlying molecular mechanisms. Methods： In in vivo study, rats with R3230 breast adenocarcinoma were sacrificed 24 h post-treatment and gross coagulation areas were compared, and next, randomized into four treatment arms （control, quercetin alone, RF alone, and combination） for Kaplan-Meier analysis of defined endpoint survival. Then the distribution and expression levels of heat shock protein 70 （HSP70）, cleaved caspase-3 and heat shock factor 1 （HSF1） were analyzed after different treatments. In in vitro study, we used quercetin to promote SK- HEP-I （hepatic） and MCF-7 （breast） cancer cell apoptosis in heat shock cell model, and siRNA was used to block c-Jun and to explore the role of activating protein-1 （AP-1） signaling pathways. Results： We found the effects of quercetin plus RFA resulted in increase on the tumor destruction/ endpoint survival （26.5±3.4 d） in vivo, compared with RF alone （17.6±2.5 d） and quercetin alone （15.7±3.1 d）. Most importantly, quercetin-induced cancer cell death required the presence of HSF1 in animal model. Furthermore, quercetin directly down-regulated expression of HSF1 in vitro, which our findings have revealed, required the activation of AP-1 signaling pathways by loss-of-function analysis using siRNA mediated targeting of c-Jun. Conclusions： These results indicated a protective role of quercetin in tumor ablation and highlighted a novel mechanism involving HSP70 with HSF1 pathway in thermal ablation of solid tumors.

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.

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.

What we know about ST13, a co-factor of heat shock protein, or a tumor suppressor?

This article is to summarize the molecular and functional analysis of the gene “suppression of tumorigenicity 13” (ST13). ST13 is in fact the gene encoding Hsp70 interacting protein (Hip), a co-factor (co-chaperone) of the 70-kDa heat shock proteins (Hsc/Hsp70). By collaborating with other positive co-factors such as Hsp40 and the Hsp70-Hsp90 organizing protein (Hop), or competing with negative co-factors such as Bcl2-associated athanogen 1 (Bag1), Hip facilitates may facilitate the chaperone function of Hsc/Hsp70 in protein folding and repair, and in controlling the activity of regulatory proteins such as steroid receptors and regulators of proliferation or apoptosis. Although the nomenclature of ST13 implies a role in the suppression of tumorigenicity (ST), to date available experimental data are not sufficient to support its role in cancer development, except for the possible down-regulation of ST13 in gastric and colorectal cancers. Further investigation of this gene at the physiological level would benefit our understanding of diseases such as endocrinological disorders, cancer, and neurodegeneration commonly associated with protein misfolding.

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.

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.

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 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.

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.

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.