• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3517-3522
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• 2015

Background: Glucose regulated protein 78 (GRP78) is a type of molecular chaperone. It is a possible candidate protein that contributes to development of drug resistance. We first examined the involvement of GRP78 in chemotherapy-resistance in human ovarian cancer cell. Materials and Methods: The expression of GRP78 mRNA and protein were examined by RT-PCR and western blotting, respectively, in human ovarian cancer cells line (HO-8910). Sensitivity of HO-8910 to paclitaxel was determined with methyl thiazolyl tetrazolium (MTT). Suppression of GRP78 expression was performed using specific small-interfering RNA (siRNA) in HO-8910 cells, and cell apoptosis was assessed by flow cytometry. Statistical analysis was performed using the SPSS 15.0 statistical package. Results: HO-8910 cells, with high basal levels of GRP78, exhibited low sensitivity to paclitaxel. The mRNA and protein levels of GRP78 were dramatically decreased at 24h, 48h and 72h after transfection and the sensitivity to paclitaxel was increased when the GRP78 gene was disturbed by specific siRNA transfection. Conclusions: The results suggested that high GRP78 expression might be one of the molecular mechanisms causing resistance to paclitaxel, and therefore siRNA of GRP78 may be useful in tumor-specific gene therapy for ovarian cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.12
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• pp.5179-5183
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• 2016

Background: Prior series investigated the expression of prepro-gastrin releasing peptide (prepro-GRP) in the peripheral blood of lung cancer patients. Our aim was to assess any prepro-GRP role as a prognostic factor for small cell lung cancer (SCLC) and NSCLC and correlations with clinical presentation and treatment outcome. Methods: A prospective study was conducted during the time period from the beginning of January 2012 till the end of January 2014. Prepro-GRP expression was analysed using a nested RT-PCR assay in peripheral blood of 62 untreated lung cancer patients attending the National Cancer Institute (NCI), Cairo University, and 30 age and sex matched healthy volunteers. Results: Among the 62 lung cancer cases, there were 24 (38.7%) SCLC, and 38 (61.3%) NSCLC (10 squamous cell carcinomas, 12 adenocarcinomas, 11 large cell carcinomas, 4 undifferentiated carcinomas, and 1 adenosquamous carcinoma). Twenty six patients (41.9%) were prepro-GRP positive. Prepro-GRP expression was higher (58.3%) among SCLC patients compared to NSCLC (squamous cell carcinoma (15.4%), large cell carcinoma (36.4%), and adenocarcinoma (25%)). Mean OS among prepro-GRP negative cases was longer than that among preprogastrin positive cases (17.6 vs 14.9 months). The mean PFS durations among preprogastrin negative versus positive cases were 7.7 vs 4.6 months (p= 0.041). No difference in response to chemotherapy was identified between the groups (p=0.983). Conclusion: Prepro-GRP is suggested to be a useful prognostic marker for lung cancer patients, especially with the fast- growing, bad prognostic SCLC type. More studies should aim at detailed understanding of the mechanisms of prepro-GRP action and its use in monitoring the response to treatment in a larger cohort.

• Biomedical Science Letters
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• v.11 no.3
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• pp.311-318
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• 2005

Grp78, discovered as one of the putative target genes of Hoxc8, is a highly conserved stress protein and functions as a molecular chaperone in the endoplasmic reticulum (ER). In order to see the stage-specific expression pattern of Grp78 during development, mouse embryos from day 7.5 to 17.5 p.c. were isolated, and RT-PCR as well as in situ hybridization was performed. When RT-PCR was performed using Grp78 specific primers, periodic expression pattern was detected. And also a region-specific expression pattern was detected with a strong expression in the trunk part of day 11.5 p.c. embryo, like that of Hoxc8. When in situ hybridization was performed, Grp78 was revealed to be expressed in the endoderm, somite, neuroepithelium cells of neural tube in early embryos. In the case of late embryos, Grp78 expression was detected in the liver, segmental bronchus within cranial lobe of lung, ossification center within the cartilage primordium of rib and vertebra, submandibular gland, as well as metanephros. These expression patterns are very much similar to those of Hoxc8. Since Hoxc8 has been reported to regulate apoptosis during organogenesis, it might be possible that the apoptotic function could have been conveyed through the expression of Grp78, implying that the Grp78 is one of the Hoxc8 downstream target genes.

• Journal of the Korean Society for Advanced Composite Structures
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• v.2 no.3
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• pp.18-24
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• 2011

In this paper, we present the load-deflection behavior of GRP pipes. GRP buried pipes are widely used in construction in the advantage of their superior mechanical and physical characteristics such as high chemical resistance, high corrosion resistance, right weight, smooth surface of the pipe, and cost effectiveness from soil-structure interaction. To design flexible pipes to be buried underground, it should be based on the ASTM D2412(2010). When applying ASTM D 2412(2010) to the design, pipe stiffness(PS) must be predetermined by the parallel-plate test which requires tedious and laborious working process. To overcome such problems, the finite element simulations for finding the load-deflection behavior of the GRP flexible pipes is installed at UTM testing machine. In the finite element simulations, basic data, such as the modulus of elasticity of the material and cross-sectional dimension, is used. From the investigation, we found that the difference between experimental result and analytical prediction is less than 15% when the pipe deflected 3% and 5% of its vertical diameter although the pipe material is not uniform across the cross-section.

• Steel and Composite Structures
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• v.30 no.5
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• pp.417-432
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• 2019

This paper presents the results of axial compression testing and numerical modeling on reinforced concrete columns (RCC) with normal concrete (NC) and high-strength concrete (HSC), RCC confined by glass-fiber reinforced plastic pipes (GRP) casing as well as carbon fiber reinforced polymer (CFRP), The major parameters evaluated in the experiments were the effects of concrete type, GRP casing and CFRP wrapping, as well as the number of CFRP layers. 12 cylindrical RCC ($150{\times}600mm$) were prepared and divided into two groups, NC and HSC. Each group was divided into two parts; with and without GRP casing. In each part, one column was without CFRP strengthening layer, a column was wrapped with one CFRP layer and another column with two CFRP layers. All columns were tested under concentrated compression load. Numerical modeling was performed using ABAQUS software and the results of which were compared with experimental findings. A good agreement was found between the results. Results indicated that the utilization of CFRP wrapping and GRP casing improved compression capacity and ductility of RCC. The addition of one and two layer-FRP wrapping increased capacity in the NC group to an average of 18.5% and 26.5% and in the HSC group to an average of 10.2% and 24.8%. Meanwhile, the utilization of GRP casing increased the capacity of the columns by 3 times in the NC group and 2.38 times in the HSC group. The results indicated that although both CFRP wrapping and GRP casing increased confinement, the GRP casing gave more increase capacity and ductility of the RCC due to higher confinement. Furthermore, the confinement effect was higher on NC group.

• Smart Structures and Systems
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• v.23 no.5
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• pp.495-506
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• 2019

This paper presents the results of axial pressure testing on reinforced concrete columns (RCCs) filled with confined normal concrete (NC) and high-strength concrete (HSC) using glass-fiber reinforced plastic pipes (GRP) casing as well as fiber reinforced polymer (FRP). This study aims to evaluate the behavior and mechanical properties of columns confined with GRP casing and FRP wrapping under pressure loads. The major parameters in the experiments were the type of concrete, the effect of GRP casing and FRP wrapping, as well as the number of FRP layers. 12 cylindrical RCCs (150*600) mm were prepared and divided into two groups, NC and HSC, and each group was divided into two parts. In each part, one column was without FRP strengthening layer, a column was wrapped with one FRP layer and another column with two FRP layers. All columns were tested under concentrated compression load. The results of the study showed that the utilization of FRP wrapping and GRP casing improved compression capacity and ductility of RCCs. The addition of one and two layers-FRP wrapping increased compression capacity in the NC group to an average of 18.5% and 26.5% and to an average of 10.2% and 24.8% in the HSC group. Meanwhile, the utilization of GRP casing increased the compression capacity of the columns by 4 times in the NC group and 3.38 times in the HSC group. The results indicated that although both FRP wrapping and GRP casing result in confinement, the GRP casing resulted in increased compression capacity and ductility of the RCCs due to higher confinement. Furthermore, the confinement effect was higher on columns made with NC.

• BMB Reports
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• v.57 no.4
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• pp.188-193
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• 2024

Gastric cancer (GC), a leading cause of cancer-related mortality, remains a significant challenge despite recent therapeutic advancements. In this study, we explore the potential of targeting cell surface glucose-regulated protein 94 (GRP94) with antibodies as a novel therapeutic approach for GC. Our comprehensive analysis of GRP94 expression across various cancer types, with a specific focus on GC, revealed a substantial overexpression of GRP94, highlighting its potential as a promising target. Through in vitro and in vivo efficacy assessments, as well as toxicological analyses, we found that K101.1, a fully human monoclonal antibody designed to specifically target cell surface GRP94, effectively inhibits GC growth and angiogenesis without causing in vivo toxicity. Furthermore, our findings indicate that K101.1 promotes the internalization and concurrent downregulation of cell surface GRP94 on GC cells. In conclusion, our study suggests that cell surface GRP94 may be a potential therapeutic target in GC, and that antibody-based targeting of cell surface GRP94 may be an effective strategy for inhibiting GRP94-mediated GC growth and angiogenesis.

• The Korean Journal of Zoology
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• v.35 no.4
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• pp.456-465
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• 1992

The 94 KDa glucose-resulsted Protein (SH 94), one of stress Proteins, is a Ca2+-binding protein in the endoplasmic reticulum (ER). In this study, the possible effect of Ca2+ on the native conformation of grp 94 was examined. When the purified grp 94 was analyzed by Sel filtration in the presence of either EGTA or CaCl2, it was eluted with apparent molecular weight (MW) of 100 KDa in both cases. When similarly analyzed with microtome or cell Ivsate, however, srp 94 was eluted with apparent IW of 200 KDa in the presence of E6TA, while with apparent MW of 100 KDa in the presence of CaCl2, indicating possible association of grp 94 with one or more other proteins in the absence of CaCl2. Consequently, immunoprecipitation with anti-grp 94 was carried out to determine which proteins specifically interact with grp 94. It is sho%un that srp 94 may interact, in a Ca2+_dependent manner. with other proteins including BiP (grp 78) which is also a stress protein in the ER.

• Journal of Life Science
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• v.15 no.1 s.68
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• pp.87-93
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• 2005

This study investigated the response of GLUT -4 and GRP-78 expression in soleus muscle of streptozotocin-induced diabetic rats by imposing different exercise intensities. F344 rats were randomly divided into 4 groups (n=15 in each group): Control (Control), diabetes-operation (DO), diabetes with low intensity exercise (DLE) and diabetes with high intensity exercise (DHE). The rats in DLE and DHE groups were exercised for 8 weeks by treadmill running. Blood glucose levels in DO were significantly higher compared to that in NORMAL whereas DLE showed the most lowest level in blood glucose among diabetic groups. Diabetic groups exhibited significantly lower level in insulin change and DLE showed significantly higher insulin level among diabetic groups. GRP-78 in DO was significantly $(167.05\%)$ higher than that in Control. GRP-78 in DLE was $139.41\%$ which is significantly higher compared to Control but when compared to DO and DHE, it was significant low. GRP-78 in DHE was $194.64\%$ which doubled the protein level in Control and showed the most highest level in all groups. GLUT-4 in DO was significantly $(33.58\%)$ higher compared to Control. GLUT-4 in DLE showed $124.58\%$ which was significant high compared to Control, DO and DHE. GLUT-4 in DHE showed $26.91\%$ compared to Control and was the most lowest level among all groups. It seems clear that chiefly low intensity exercise benefits diabetic patients in controlling blood glucose. It was concluded that low intensity exercise induces translocation of GLUT-4 which results in increased blood inflow, thus GRP-78 expression is decreased.

• BMB Reports
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• v.50 no.12
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• pp.628-633
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• 2017

Gastrin-releasing peptide (GRP) has been reported to be implicated in the pathogenesis of inflammatory disorders. The migration and proliferation of vascular smooth muscle cells (VSMCs) are key components of vascular inflammation that leads to the development of atherosclerosis. The present study aimed to investigate the molecular effect of GRP on VSMC proliferation and migration. We report that GRP significantly enhanced the proliferation and migration of rat VSMCs. GRP increased mRNA and protein expression of matrix metalloproteinase-2 and -9 (MMP-2/9) in VSMCs. The induction of MMP-2/9 by GRP was regulated by the activation of the signal transducer and activator of transcription-3 (STAT3). In addition, STAT3-knockdown of VSMCs by siRNA or blockade of the GRP receptor inhibited GRP-induced migration of VSMCs. Taken together, our findings indicate that GRP promotes the migration of VSMCs through upregulation of MMP-2/9 via STAT3 activation.