Animals ; Ethanol ; therapeutic use ; HSP70 Heat-Shock Proteins ; therapeutic use ; Humans ; Ischemic Preconditioning ; Liver ; blood supply ; Reperfusion Injury ; prevention & control

Heat shock factor 1 (HSF1) is the key protein in regulating stress response. It can be activated under heat, oxidative or another stress conditions. Dominant-positive and dominant-negative HSF1 are two types of HSF1 mutants. Both of them gain the DNA binding activity in the absence of stress. In addition, dominant-positive HSF1 acquires transcriptional activity, which dominant-negative HSF1 does not acquire. In this paper, the progress of using these HSF1 mutants in the research of cancer, neurodegenerative disorders and cardiovascular diseases will be discussed.
Genetic Therapy ; Heat-Shock Proteins ; genetics ; therapeutic use ; Humans ; Mutant Proteins ; genetics ; Neoplasms ; therapy ; Neurodegenerative Diseases ; therapy

Heat-shock protein gp96 associates with antigenic peptides derived from tumor and virus. Exogenous gp96-peptide complexes are taken up by antigen-presenting cells through interaction with its receptor CD91 on the cell surface, and cross-present antigenic peptides to MHC class I molecules by a peptide relay line in the endoplasmic reticulum for specific T-cell activation. Meanwhile, gp96 has been shown to initiate innate immune responses through interaction with toll-like receptor 2 and toll-like receptor 4. Recent studies have shown a gp96-mediated immune balance between CTL and Tregs. With the further understanding of counteracting immunosuppressive mechanisms in gp96-induced cellular immune responses, and establishment of high level production of recombinant gp96 by the yeast, gp96 appears to be a promising candidate for designing effective therapeutic vaccines against tumor and infectious diseases.
Animals ; Communicable Diseases ; therapy ; Heat-Shock Proteins ; immunology ; therapeutic use ; Humans ; Immunotherapy, Active ; methods ; Neoplasms ; therapy ; T-Lymphocytes, Regulatory ; immunology

OBJECTIVETo study the significance of HSP47 gene in the development of pathological scar.

METHODSThe nude mice were used to reconstruct animal model of pathological scar. 16 days later, the mixture of recombinant HSP47siRNA and liposome was injected into the pathological scar in experimental group. In the control group, 0.25 ml PBS was injected intraperitoneally. 7 days after injection, the specimens were collected for detection of mRNA of HSP47, the collagen and for immunohistochemical study.

RESULTSIn the control and experimental group, the collagen content was (91.71 +/- 1.24)% and (82.12 +/- 4.79)%, respectively; the expression of HSP47mRNA was 1 042 862.01 +/- 604 194.36 and 306 123.68 +/- 105 857.08, respectively; the expression of collagen I mRNA was 10 228 614.70 +/- 2 532 879.04 and 6 011 841.97 +/- 2 886 897.17, respectively;the scar volume was (255.60 +/- 21.34) mm3 and (132.99 +/- 24.06) mm3, respectively. All the above results showed significant difference between the two groups (P < 0.05).

CONCLUSIONSThe collagen production can be reduced through suppression of the expression of HSP47 gene. It indicates that HSP47 gene enhance the development of keloid and could be used as the target of treatment.

Animals ; Cicatrix ; genetics ; pathology ; therapy ; Collagen ; biosynthesis ; Genetic Therapy ; Genetic Vectors ; HSP47 Heat-Shock Proteins ; genetics ; therapeutic use ; Liposomes ; therapeutic use ; Mice ; Mice, Nude ; RNA, Messenger ; genetics ; RNA, Small Interfering ; therapeutic use

Heat shock protein gp96 isolated from tumor tissues holds great promise for tumor immunotherapy. However, at present only very limited amount of gp96 protein can be isolated from tumor tissues. Here, we reconstituted the yeast-expressed gp96 (recombinant gp96, rgp96) with B16.F10 melanoma antigens in vitro to prepare new gp96 tumor vaccine on large-scale, and analyzed its induction of specific anti-tumor immunoresponses by ELISPOT, IFN-gamma intracellular staining and cytotoxicity assays. Immunization with rgp96-tumor antigen complexes significantly inhibited B16 tumor growth compared with either rgp96 or tumor antigens alone and led to enhancement of tumor-specific T-cell activities, which was found similar to that of tumor tissue derived gp96. Our results therefore may provide bases for large-scale preparation of the new generation of gp96 tumor vaccines.
Animals ; Cancer Vaccines ; biosynthesis ; genetics ; immunology ; therapeutic use ; Female ; Heat-Shock Proteins ; biosynthesis ; genetics ; immunology ; therapeutic use ; Melanoma, Experimental ; therapy ; Mice ; Mice, Inbred C57BL ; Neoplasm Transplantation ; Recombinant Fusion Proteins ; biosynthesis ; genetics ; immunology ; therapeutic use ; Skin Neoplasms ; therapy ; Yeasts ; genetics ; metabolism

OBJECTIVETo investigate the association between expressions of HSP70, HSP90 and efficacy of chemotherapy in colorectal cancer patients with unresectable liver metastasis.

METHODSData of 52 colorectal cancer cases, whose primary colorectal focuses were resected but hepatic metastatic tumors were unresectable, were reviewed retrospectively. All the patients underwent FOLFOX4 regimen well. Immunohistochemistry assay was applied to determine the expressions of HSP70 and HSP90 in primary focus tissues. The number and size of hepatic metastatic tumors pre- and post-chemotherapy were compared by CT scanning.

RESULTSPartial remission(PR) rate was 33.3% in cases with up-regulated expression of HSP70, while 64.5% in cases with down-regulated expression of HSP70, whose difference was significant. PR rate was 50% in cases with up-regulated expression of HSP90, and 53.1% in the others with down-regulated expression of HSP90, whose difference was not significant.

CONCLUSIONSFOLFOX4 regimen has advantages in cases with lower HSP70 expression over those with higher HSP70 expression. HSP90 expression level is not associated with the efficacy of FOLFOX4 regimen.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Colorectal Neoplasms ; drug therapy ; metabolism ; pathology ; Female ; HSP70 Heat-Shock Proteins ; metabolism ; HSP90 Heat-Shock Proteins ; metabolism ; Humans ; Liver Neoplasms ; drug therapy ; metabolism ; secondary ; Male ; Middle Aged ; Prognosis ; Treatment Outcome

Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Heat Stress Disorders ; drug therapy ; metabolism ; Hypothalamus ; metabolism ; Male ; Neurotensin ; metabolism ; Phytotherapy ; Rats ; Rats, Wistar ; Tablets

Myotonic dystrophy is a muscular disorder characterized by muscle weakness and myotonia. Myotonia manifests with abnormally slow relaxation after strong voluntary contraction of the muscles. In our previous study we reported that quinine sulfate provided therapeutic benefit to myotonia and a home exercise program based on muscle strengthening exercises improved muscle strength. The purpose of this study was to determine the effect of a multi-therapeutic program in patients with myotonic dystrophy. For six months, seven patients with myotonic dystrophy received heat therapy, were given psychologic intervention using relaxation techniques, were trained at home, and were given quinine sulfate. The changes in muscle strength and relaxation time between the post-six-months home exercise program combined with quinine sulfate therapy, and the post-six months multi-therapeutic program, were assessed from the first dorsal interossei, the elbow flexors, and the knee extensors. The results were as follows: 1) The mean muscle strength of the each of the three muscles after the six months multi-therapeutic program was improved but was not significant compared with the post-six-months home exercise program combined with quinine sulfate therapy. 2) The mean relaxation time of each of the three muscles after the six months multi-therapeutic program was significantly reduced compared with the home exercise program combined with quinine sulfate therapy. In conclusion, the multi-therapeutic program undertaken in this study was the better program for the patients with myotonic dystrophy.
Adolescent ; Adult ; Female ; Heat/therapeutic use ; Human ; Male ; Middle Age ; *Muscle Relaxation ; Muscles/*physiopathology ; Myotonic Dystrophy/*physiopathology/*rehabilitation ; Relaxation Techniques ; Support, Non-U.S. Gov't ; Time Factors

OBJECTIVETo develop a new vaccine expressing membrane-bound heat shock protein 70 (mbHSP70) and further study its antitumor therapeutic effect.

METHODThe pre- established vector expressing mbHSP70 was transfected into CT26 cells of colorectal cancer. After the CT26 cells were incubated with 900 microg/ml G418, the sub-clones resistant to G418 were harvested and the HSP70 positive clones were selected by limiting dilution. The clones were amplified and inactivated, thereby the vaccine expressing mbHSP70 was prepared. Lymphocyte proliferation stimulated by the vaccines, NK and CTL activity was observed. The antitumor efficacy of vaccine was observed in BALB/c mice model with colorectal cancer.

RESULTSThe laser confocal microscopy and flow cytometry showed that there existed much HSP70 on the vaccine membrane surface. The HSP70 gene-modified vaccine displayed augmented lymphocyte proliferation and higher NK and CTL activity in vitro,and marked tumor suppression and prolonged survival time of the vaccinated micein vivo, when compared with its counterpart. Furthermore, mbHSP70-expression vaccine elicited lymphocyte proliferation most intensively, generated the highest NK and CTL activity as well as the strongest antitumor effect, and prolonged survival time of the vaccinated mice.

CONCLUSIONA new vaccine expressing mbHSP70 has more potent antitumor immunity and better therapeutic efficacy than HSP70 gene-modified vaccine did.

Animals ; Cancer Vaccines ; therapeutic use ; Cell Membrane ; immunology ; metabolism ; HSP70 Heat-Shock Proteins ; immunology ; Immunotherapy ; Mice ; Mice, Inbred BALB C ; Neoplasms, Experimental ; therapy ; Transfection

OBJECTIVETo investigate the protective effect of ulinastatin (UTI) against acute lung injury induced by heatstroke in mice.

METHODSSixty C57/BL6 mice were randomly divided into 6 groups, with 10 mice in each: control group, heatstroke group, UTI pretreatment group, saline pretreatment group, UTI post-treatment group, saline post-treatment group. The control mice were housed at a controlled room temperature of (22∓1) degrees; celsius, and the other groups were placed inside a temperature and humidity controlled chamber pre-set at 37 degrees; celsius and 60%. The two UTI groups were intraperitoneally injected with UTI at 5×10(4) U/kg 10 min before or after heat stress, and the two saline groups were given then equal amounts of saline in the same manner. The core body temperature of mice was monitored by a mercury thermometer every 30 min in the first 1.5 h during heating. The core temperature was measured, then every 15 min until it reached 42.7 degrees; celsius, which was taken as the onset of heatstroke. The animals were allowed to recover passively at ambient temperature for 6 h. The lung histopathological changes, protein concentration in BALF, lung wet/dry weight ratios, lung water content, and pulmonary microvascular permeability were assayed after 6 h of recovery at 37 degrees;celsius.

RESULTSCompared with the control group, the heatstroke model group and two saline groups displayed more severe lung damage and pathological morphology changes, and the lung wet/dry weight ratio, protein concentration in BALF, lung water content and pulmonary microvascular permeability were also significantly increased. These effects were significantly alleviated in UTI treated group. Pretreat ment with UTI significantly prolonged the time to Tc≥42.7 degrees; celsius but had no effect on lung injury induced by heatstroke.

CONCLUSIONUTI can reduce the pulmonary edema and inflammatory exudation in acute lung injury caused by heatstroke.

Acute Lung Injury ; drug therapy ; physiopathology ; Animals ; Body Temperature ; Bronchoalveolar Lavage Fluid ; chemistry ; Edema ; prevention & control ; Glycoproteins ; therapeutic use ; Heat Stroke ; physiopathology ; Lung ; pathology ; Mice ; Mice, Inbred C57BL