• Molecules and Cells
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• 제23권1호
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• pp.23-29
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• 2007

Cyclic AMP-responsive element binding protein (CREB) is known to be associated with angiogenesis. In the present study we investigated the possible role of CREB in the expression of vascular endothelial growth factor (VEGF) by mouse macrophages. Over-expression of CREB increased VEGF secretion by cells of the RAW264.7 mouse macrophage cell line. It also increased the promoter activity of a mouse reporter driven by the VEGF promoter, while a dominant negative CREB (DN-CREB) abrogated the activity, suggesting that CREB mediates VEGF transcription. Forskolin, an adenylyl cyclase activator, stimulated VEGF transcription, and the PKA inhibitor H89 abolished this effect. IFN-${\gamma}$, a potent cytokine, stimulated VEGF expression only in part through the PKA-CREB pathway. These results indicate that PKA phosphorylates CREB and so induces VEGF gene expression. An analysis of mutant promoters revealed that one of the putative CREB responsive elements (CREs), at -399 ~ -388 in the promoter, is critical for CREB-mediated VEGF promoter activity, and the significance of this CRE was confirmed by chromatin immunoprecipitation assays.

• Toxicological Research
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• 제29권3호
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• pp.195-201
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• 2013

The anti-inflammatory effects of glycosaminoglycan (GAG) derived from Isaria sinclairii (IS) and of IS extracts were investigated in a complete Freund's adjuvant (CFA)-treated chronic arthritis rat model. Groups of rats were treated orally with 30 mg/kg one of the following: [1] saline control, extracts of [2] water-IS, [3] methanol-IS, [4] butanol-IS, [5] ethyl acetate-IS, or [6] Indomethacin(R) as the positive control for a period of two weeks. The anti-paw edema effects of the individual extracts were in the following order: water-IS ex. > methanol ex. > butanol ex. > ethyl acetate ex. The water/methanol extract from I. sinclairii remarkably inhibited UV-mediated upregulation of NF-${\kappa}B$ activity in transfected HaCaT cells. GAG as a water-soluble alcohol precipitated fraction also produced a noticeable anti-edema effect. This GAG also inhibited the pro-inflammatory cytokine levels of prostaglandin $E_2$-stimulated lipopolysaccharide in LAW 264.7 cells, cytokine TNF-${\alpha}$ production in splenocytes, and atherogenesis cytokine levels of vascular endothelial growth factor (VEGF) production in HUVEC cells in a dose-dependent manner. In the histological analysis, the LV dorsal root ganglion, including the articular cartilage, and linked to the paw-treated IS GAG, was repaired against CFA-induced cartilage destruction. Combined treatment with Indomethacin(R) (5 mg/kg) and IS GAG (10 mg/kg) also more effectively inhibited CFA-induced paw edema at 3 hr, 24 hr, and 48 hr to levels comparable to the anti-inflammatory drug, indomethacin. Thus, the IS GAG described here holds great promise as an anti-inflammatory drug in the future.

• 대한한방내과학회지
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• 제24권2_4호
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• pp.1067-1074
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• 2003

Objectives : This study was designed to evaluate the effects of traditional oriental therapies(TOT) on advanced gastric cancer(AGC) patient with metastasis to liver. Methods : We retrospectively analyzed the medical record of a case of AGC patient in stage IV with metastasis to liver who had been treated with TOT for 5 months continuously in East-West Cancer Center of Oriental Hospital of Daejeon University from 5 March 2003 through 22 July 2003. Results : After treated with TOT for the 5 months, most of symptoms were disappeared or improved and tumor size was decreased on abdominal CT compared with the previous result. The hematological results and tumor markers were not increased. Conclusions : From the above results, it could be suggested that TOT have effects on improving symptoms and quality of life as a supportive or curative therapy for AGC patients.

• Journal of Korean Neurosurgical Society
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• 제40권6호
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• pp.428-433
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• 2006

Objective : We investigated the pattern of glucose uptake in meningiomas using $^{18}F$-fluoro-2-deoxy-D-glucose[FDG] PET/CT. It was hypothesized that the degree of glucose uptake in each tumor could predict the histologic grade. Methods : In 19 patients with meningiomas, the Ki-67 proliferative index, standardized uptake values[SUV] of FDG uptake, tumor to contralateral gray matter ratio[TGR] of SUV, tumor size, edema grade, vascular endothelial growth factor[VEGF] expression, histopathologic grade and the blood supply pattern were assessed. Results : Of the 19 meningiomas, 8 were meningothelial, 1 fibrous, 2 transitional, 1 psammomatous, 2 angiomatous, and 5 atypical. The tumor proliferative index of Ki-67, tumor size, and peritumoral edema were larger in the histopathologic grade-2 meninigiomas than in the grade-1 meningioma group. There were no significant differences in SUV and TGR between two groups. Tumor size and peritumoral edema were significantly larger in VEGF-positive tumors than in negative tumors. Conventional angiography was performed in 12 patients. Dural supply was noted predominantly in 2 patients. Four patients had mainly pial cortical supply patterns. In tumors with more pial supply, VEGF was more frequently positive. There was a significant relation between SUV and Ki-67 and between SUV and peritumoral edema. Conclusion : We found FOG uptake in meningiomas is associated with proliferative potential, however, no clear limits of SUV and TGR can be set to distinguish between grade-1 and grade-2 meningiomas, which makes the assessment of malignancy grade using PET scan metabolic imaging difficult in individual cases.

• The Journal of Korean Physical Therapy
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• 제15권3호
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• pp.16-44
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• 2003

Skeletal muscle regeneration is a vital process for various muscle myopathies and muscular adaptation to physiological overload. Angiogenesis is the key event in the process of muscle regeneration, and vascular endothelial growth factor(VEGF) plays an important role in it. The purpose of this study was to evaluate the effect of GaAlAs(830nm) laser and immunoreactivity of VEGF on angiogenesis after muscle contusion injury. Muscle contusion injury was induced in the triceps surae muscle by dropping a metal bead(31.4g). GaAlAs laser irradiation(power 20 mW, frequency 2000 Hz, treatment time 15 min) was applied directly to the skin of injured muscle daily for seven days. The experimental group I was irradiated immediately by laser after injury, whereas the experimental group II was irradiated after 1 day of injury. The control group was non-irradiated. The results of this study were as follows. 1. In morphological observation, there were no significant changes in experimental and control groups for 7 days. At 3 days, however, the splited muscle fibers were observed in experimental groups, and the muscle atrophy and granular tissue viewed at 7 days in control group. 2. The VEGF was expressed in muscle fiber that located in the interspace between gastrocnemius and soleus muscles. As the time coursed, the immunoreactivity of VEGF also seemed to be strong in the individual muscle fibers. 3. The experimental group I & II showed higher immunoreactivity of VEGF than control group(p<0.05). Then, the experimental group I showed higher than group II especially(p<0.05). These data suggest GaAlAs semiconduct diode laser irradiation(830nm) enhanced angiogenesis in the skeletal muscle induced contusion injury, and immediate laser irradiation after injury promoted the angiogenesis greatly than after 1 day of injury.

• 생약학회지
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• 제37권2호통권145호
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• pp.110-115
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• 2006

Melittia inouei (Yuri Nabang) larvae are used as a crude drug in East Asia for treating stomach cancer and inflammation, and currently reared as a pharmaceutical insect in Jejudo, Korea. This study evaluated the immuno-modulating activity of these extracts, by determining the level of, cytokine production from mouse splenocytes stimulated with the extracts. The Melittia inouei larvae extracts did not induce the splenocyte proliferation. On the other hand, they stimulated the splenocytes to produce cytokines such as $TNF-{\alpha}$, whereas they did not stimulate IL10, IL12 or $IFN-{\gamma}$. The aqueous portion of its plant (Tri-chosanthis kirilowii) extract (sap) was found to be a potent inducer of NO production from the CPAE cells. However, it showed weak inhibitory effects on vascular endothelial growth factor (VEGF) production from splenocytes. These data suggests that a Melittia inouei larvae extract immune modulatory activity in cytokine prodcutions such as $TNF-{\alpha}$ and VEGF which might be related its anticancer effect.

• Journal of Microbiology and Biotechnology
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• 제28권3호
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• pp.367-374
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• 2018

RNA interference provides an effective tool for developing antitumor therapies. Cell-penetrating peptides (CPPs) are delivery vectors widely used to efficiently transport small-interfering RNA (siRNA) to intracellular targets. In this study, we investigated the efficacy of the cancer-specific CPP carrier BR2 to specifically transport siRNA to cancer-target cells. Our results showed that BR2 formed a complex with anti-vascular endothelial growth factor siRNA (siVEGF) that exhibited the appropriate size and surface charge for in vivo treatment. Additionally, the BR2-VEGF siRNA complex exhibited significant serum stability and high levels of gene-silencing effects in vitro. Moreover, the transfection efficiency of the complex into a cancer cell line was higher than that observed in non-cancer cell lines, resulting in downregulated intracellular VEGF levels in HeLa cells and comprehensively improved antitumor efficacy in the absence of significant toxicity. These results indicated that BR2 has significant potential for the safe, efficient, and specific delivery of siRNA for diverse applications.

• Asian Pacific Journal of Cancer Prevention
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• 제15권16호
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• pp.6565-6570
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• 2014

Objective: To observe the curative effects of rh-endostatin combined with DP regimen in treating patients with advanced esophageal cancer and analyze the correlation of CT perfusion (CTP) parameters and the expression of vascular endothelial growth factor (VEGF). Methods: Twenty patients with esophageal cancer confirmed pathologically were randomly divided into combined treatment (rh-endostatin+DP regimen) group and single chemotherapy group, 10 patients in each group, respectively. All patients were given conventional CT examination and CTP imaging for primary tumor. The level of VEGF, the size of tumor and CTP parameters (BF, BV, PS and MTT) before treatment and after 2 cycles of treatment were determined for the comparison and the correlation between CTP parameters and VEGF expression was analyzed. Results: the therapeutic effect of rh-endostatin+DP regimen group was superior to single chemotherapy group. VEGF level after treatment in rh-endostatin+DP regimen group was obviously lower than single chemotherapy group (P<0.01). The expression of VEGF had positive correlation with BF and BV but negative correlation with MTT. Compared with treatment before for rh-endostatin+DP regimen group, BF, BV and PS decreased while MTT increased after treatment (P<0.05). However, there were no significant differences between treatment before and after treatment in single chemotherapy (P>0.05). Conclusions: Rh-endostatin can down-regulate the expression of VEGF in esophageal cancer, change the state of hypertransfusion and high permeability of tumor vessels and had the better curative effect and slighter adverse reactions when combined with chemotherapy.

• 대한의용생체공학회:의공학회지
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• 제31권1호
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• pp.81-86
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• 2010

Laser irradiation is known to affect various tissues such as skin, bone, nerve, and skeletal muscle. Laser irradiation promotes ATP synthesis, facilitates wound healing, and stimulates cell proliferation and angiogenesis. In skeletal muscle, laser irradiation is related to the proliferation of skeletal muscle satellite cells. Normal skeletal muscle contains remodeling capacity from myogenic cells that are derived from mononuclear satellite cells. Their processes are activated by the expression of genes related with myogenesis such as muscle-specific transcription factors (MyoD and Myf5) and VEGF (vascular endothelial growth factor). In this study, we hypothesized that laser irradiation would enhance and regulate muscle cell proliferation and regeneration through modulation of the gene expressions related with the differentiation of skeletal muscle satellite cells. $C_2C_{12}$ myoblastic cells were exposed to continuous/non-continuous laser irradiation (660nm/808nm) for 10 minutes daily for either 1 day or 5 days. After laser irradiation, cell proliferation and gene expression (MyoD, Myf5, VEGF) were quantified. Continuous 660nm laser irradiation significantly increased cell proliferation and gene expression compared to control, continuous 808nm laser irradiation, and non-continuous 660nm laser irradiation groups. These results indicate that continuous 660nm laser irradiation can be applied to the treatment and regeneration of skeletal muscle tissue.

• Tuberculosis and Respiratory Diseases
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• 제78권3호
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• pp.239-245
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• 2015

Background: Chronic obstructive pulmonary disease is characterized by emphysema, chronic bronchitis, and small airway remodeling. The alveolar destruction associated with emphysema cannot be repaired by current clinical practices. Stem cell therapy has been successfully used in animal models of cigarette smoke- and elastase-induced emphysema. However, the optimal dose of mesenchymal stem cells (MSCs) for the most effective therapy has not yet been determined. It is vital to determine the optimal dose of MSCs for clinical application in emphysema cases. Methods: In the present study, we evaluated the therapeutic effects of various doses of MSCs on elastase-induced emphysema in mice. When 3 different doses of MSCs were intravenously injected into mice treated with elastase, only $5{\times}10^4$ MSCs showed a significant effect on the emphysematous mouse lung. We also identified action mechanisms of MSCs based on apoptosis, lung regeneration, and protease/antiprotease imbalance. Results: The MSCs were not related with caspase-3/7 dependent apoptosis. But activity of matrix metalloproteinase 9 increased by emphysematous lung was decreased by intravenously injected MSCs. Vascular endothelial growth factor were also increased in lung from MSC injected mice, as compared to un-injected mice. Conclusion: This is the first study on the optimal dose of MSCs as a therapeutic candidate. This data may provide important basic data for determining dosage in clinical application of MSCs in emphysema patients.