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. 相似文献
HER2 receptor dimerization is a critical step in the HER2 activation process. Here, we demonstrated that heat shock protein gp96 on cell membrane interacts with HER2, facilitates HER2 dimerization and promotes cell proliferation. Cell membrane gp96 levels were observed to correlate with HER2 phosphorylation in primary breast tumors. Finally, we provide evidence that targeting gp96 with a specific monoclonal antibody led to decreased cell growth and increased apoptosis in vitro, and suppression of tumor growth in vivo. Our work represents a new therapeutic strategy for inhibiting HER2 signaling in cancer. 相似文献
Brain metastasis is a devastating problem in patients with breast, lung and melanoma tumors. GRP94 and FN14 are predictive biomarkers over-expressed in primary breast carcinomas that metastasized in brain. To further validate these brain metastasis biomarkers, we performed a multicenter study including 318 patients with breast carcinomas. Among these patients, there were 138 patients with metastasis, of whom 84 had brain metastasis. The likelihood of developing brain metastasis increased by 5.24-fold (95%CI 2.83–9.71) and 2.55- (95%CI 1.52–4.3) in the presence of FN14 and GRP94, respectively. Moreover, FN14 was more sensitive than ErbB2 (38.27 vs. 24.68) with similar specificity (89.43 vs. 89.55) to predict brain metastasis and had identical prognostic value than triple negative patients (p < 0.0001). Furthermore, we used GRP94 and FN14 pathways and GUILD, a network-based disease-gene prioritization program, to pinpoint the genes likely to be therapeutic targets, which resulted in FN14 as the main modulator and thalidomide as the best scored drug. The treatment of mice with brain metastasis improves survival decreasing reactive astrocytes and angiogenesis, and down-regulate FN14 and its ligand TWEAK. In conclusion our results indicate that FN14 and GRP94 are prediction/prognosis markers which open up new possibilities for preventing/treating brain metastasis. 相似文献
An annealing procedure is a heat treatment process to improve the mechanical properties of cobalt-chromium (Co-Cr) alloys. However, information is lacking about the effect of the annealing process on the bonding ability of ceramic to Co-Cr alloys fabricated by rapid prototyping.
Purpose
The purpose of this in vitro study was to evaluate the effects of the fabrication techniques and the annealing procedure on the shear bond strength of ceramic to Co-Cr alloys fabricated by different techniques.
Material and methods
Ninety-six cylindrical specimens (10-mm diameter, 10-mm height) made of Co-Cr alloy were prepared by casting (C), milling (M), direct process powder-bed (LaserCUSING) with and without annealing (CL+, CL), and direct metal laser sintering (DMLS) with annealing (EL+) and without annealing (EL). After the application of ceramic to the metal specimens, the metal-ceramic bond strength was assessed using a shear force test at a crosshead speed of 0.5 mm/min. Shear bond strength values were statistically analyzed by 1-way ANOVA and Tukey multiple comparison tests (α=.05).
Results
Although statistically significant differences were found among the 3 groups (M, 29.87 ±2.06; EL, 38.92 ±2.04; and CL+, 40.93 ±2.21; P=.002), no significant differences were found among the others (P>.05). The debonding surfaces of all specimens exhibited mixed failure mode.
Conclusions
These results showed that the direct process powder-bed method is promising in terms of metal-ceramic bonding ability. The manufacturing technique of Co-Cr alloys and the annealing process influence metal-ceramic bonding. 相似文献
Objective: The onset of essential hypertension is the result of a combination of genetic factors and the environment. The nuclear factor (NF)-κB1-94ins/del ATTG locus polymorphism is associated with the occurrence of various diseases. The purpose of this study was to find out the relationship between the NF-κB1-94ins/del ATTG locus polymorphism and the risk of hypertension in the Chinese Han population.
Methods: A total of 585 Chinese Han patients with essential hypertension and 585 Chinese Han healthy volunteers were recruited. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to analyze the genotype of the NF-κB1-94ins/del ATTG locus in all the subjects.
Results: For the NF-κB1-94ins/del ATTG locus, the dominant (adjusted odds ratio [OR] = 1.31, 95% confidence interval [CI] = 1.13–1.54, P < 0.001), recessive (adjusted OR = 1.17, 95% CI = 1.02–1.32, P = 0.03) and additive (adjusted OR = 1.19, 95% CI = 1.03–1.36, P = 0.01) models showed significant increase in the risk of hypertension. The NF-κB1-94ins/del ATTG locus II genotype was an independent risk factor for hypertension (OR = 1.15, 95% CI = 0.78–1.69, P = 0.02). The interaction between the NF-κB1-94ins/del ATTG locus polymorphism and BMI, alcohol consumption, and diabetes significantly increased the risk of hypertension (OR = 1.71, 95% CI = 1.26–1.86, P < 0.01).
Conclusion: The NF-κB1-94ins/del ATTG polymorphism is an independent risk factor for essential hypertension. The NF-κB1-94ins/del ATTG locus, obesity, drinking, and diabetes also interact to yield a higher risk of hypertension. 相似文献
Bacteriophage (phage), viruses that infect bacteria only, have become promising vectors for targeted systemic delivery of genes to cancer, although, with poor efficiency. We previously designed an improved phage vector by incorporating cis genetic elements of adeno-associated virus (AAV). This novel AAV/phage hybrid (AAVP) specifically targeted systemic delivery of therapeutic genes into tumors. To advance the AAVP vector, we recently introduced the stress-inducible Grp78 tumor specific promoter and found that this dual tumor-targeted AAVP provides persistent gene expression, over time, in cancer cells compared to silenced gene expression from the CMV promoter in the parental AAVP. Herein, we investigated the effect of histone deacetylation and DNA methylation on AAVP-mediated gene expression in cancer cells and explored the effect of cell confluence state on AAVP gene expression efficacy. Using a combination of AAVP expressing the GFP reporter gene, flow cytometry, inhibitors of histone deacetylation, and DNA methylation, we have demonstrated that histone deacetylation and DNA methylation are associated with silencing of gene expression from the CMV promoter in the parental AAVP. Importantly, inhibitors of histone deacetylases boost gene expression in cancer cells from the Grp78 promoter in the dual tumor-targeted AAVP. However, cell confluence had no effect on AAVP-guided gene expression. Our findings prove that combination of histone deacetylase inhibitor drugs with the Grp78 promoter is an effective approach to improve AAVP-mediated gene expression in cancer cells and should be considered for AAVP-based clinical cancer gene therapy. 相似文献
Summary The pathogenicity of a strain of parainfluenza type 1 virus, isolated from the cultured brain cells from multiple sclerosis patients and designated as 6/94 virus, was studied in mouse brain.Selective degeneration of cerebral white matter, preceded by mononuclear cell infiltration, and ependymitis were prominent pathological features of the mouse intracerebrally inoculated with 6/94 virus. After inactivation by ultraviolet light the virus was still capable of producing the inflammatory and degenerative white matter lesions, although the severity of ependymitis was substantially reduced.This investigation was supported in part by funds from the National Multiple Sclerosis Society, research grant NS-11036 from the National Institute of Neurological Disease and Stroke and funds from the John A. Hartford Foundation, Inc. 相似文献