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간 세포암에서 VEGF, TGF-β1, b-FGF 발현의 의의
김성용,남충현,주종우,채만규,백무준,이문수,김형철,안현철,김홍수,김창진,김창호 순천향의학연구소 2001 Journal of Soonchunhyang Medical Science Vol.7 No.1
Purpose: Angiogenesis is important for the proliferation and the metastasis of solid tumors. The growth of a solid tumor is widely recognized to depend on the process of neovascularrozation. Without angiogenesis, tumors cease to grow beyond even a few milimeters in diameter. It has been shown that tumor vascular density is an independent prognostic marker in several types of human tumors and is known to correlate with poor prognosis. To date, many angiogenic factors have been identified, such as transforming growth factor-α(TGF-α), transforming growth factor-β(TGF-β), fibroblast growth factor family(FGF), vascular endothelial growth factor(VEGF), platelet derived endothelial cell growth factor(PD-ECGF), tumor necrosis factor-α(TNF-α), and angiogenin. Hepatocellular carcinoma(HCC) is the second most common tumor in Korean males and is known as a typical hypervascular tumor with frequent portal vein invastion. The authors identified the expreesion of VEGF, TGF-β1, and b-FGF in HCC specimens and evaluated the relationship between these growth factors and the clinicopathologic characteristics of HCC. Method: We reviewed the medical records of 30 patients who were diagnosed as hepatocellular carinoma treated with hepatic resection between January 1994 and December 1998 in Soonchunhyang University Chunan Hospital. The selection of the cases was decided according to the condition of paraffin block fixation. The prognostic factors such as age, sex, tumor size, concentration of serum α-fetoprotein, presence of liver cirrhosis, presence of tumor emboli in portal vein, TMN stage, amount of transfusion during the operation, hepatitis B virus(HBV) infection, and Edmonson-Steiner(E-S) grade were investigated. Relationship between the prognostic factors and the immunopathologic expression of the TGF-β1, b-FGF, and VEGF was examined. Result: Thirty patients (24 males, 6 females) were included in the current study. The patient's mean age was 50.6 years and the age ranged from 36 to 65 years. The mean size of the tumor was found to be 5.2cm. All the patients were follewed up for 7 to 63 months. Child's classification A patients were 23(76.7%)cases, B patients were 7(23.3%)cases, and C was none. Immunohistochemical staining of HCC tumor mass in VEGF expression patients were 17(56.7%), b-FGF expression patients were 10(33.3%), and TGF-β1 expression patients were 10(33.3%). VEGF expression or more than one positive expression among the three factors correlated with tumor size and the stage of HCC but did not correlated with other clinicopathological characteristics. TGF-β1 and b-FGF did not correlate with any clinicopathological characteristics. Conclusion: The results suggest that the expression of VEGF or more than one positive expression among the three factors in HCC cells may be a significant prognostic factor of HCC.
Fibroblast Growth Factor 11 Inhibits Hepatitis B Virus Gene Expression Through FXRα Suppression
Seong Mi So,Jang Jeong Ah,Jeong Ye Rim,Kim Ye Bin,Kyaw Yi Yi,Kong Hee Jeong,Lee Jung-Hyun,Cheong JaeHun 한국미생물학회 2023 The journal of microbiology Vol.61 No.7
Fibroblast growth factor 11 (FGF11) is a member of the intracellular FGF family, which shows different signal transmission compared with other FGF superfamily members. The molecular function of FGF11 is not clearly understood. In this study, we identified the inhibitory effect of FGF11 on hepatitis B virus (HBV) gene expression through transcriptional suppression. FGF11 decreased the mRNA and protein expression of HBV genes in liver cells. While the nuclear receptor FXRα1 increased HBV promoter transactivation, FGF11 decreased the FXRα-mediated gene induction of the HBV promoter by the FXRα agonist. Reduced endogenous levels of FXRα by siRNA and the dominant negative mutant protein (aa 1–187 without ligand binding domain) of FXRα expression indicated that HBV gene suppression by FGF11 is dependent on FXRα inhibition. In addition, FGF11 interacts with FXRα protein and reduces FXRα protein stability. These results indicate that FGF11 inhibits HBV replicative expression through the liver cell-specific transcription factor, FXRα, and suppresses HBV promoter activity. Our findings may contribute to the establishment of better regimens for the treatment of chronic HBV infections by including FGF11 to alter the bile acid mediated FXR pathway.
Yoo Hwa Seung,Lee Nam Heon,Cho Jung Hyo,Lee Yeon Weol,Son Chang Gue,Kang Wee Chang,Cho Chong Kwan The Society of Korean Medicine 2005 대한한의학회지 Vol.26 No.4
Objectives: Recently, angiogenesis has gained an increasing interest as a prognostic factor in breast cancer. In this study we aimed to assess the anti angiogenic effects of HAD, a botanical anticancer remedy which has been prescribed in Daejeon University Oriental Hospital in Korea, on patients with breast carcinoma by measuring the serum vascular endothelial growth factor (VEGF), basic fibroblast growth factor (b-FGF) and platelets levels. Methods: The study included 26 consecutive breast cancer patients (mean age$\pm$standard deviation: 47.5$\pm$8.7 years) with stage II to IV disease who were treated with HAD (mean duration $\pm$ standard deviation: 264.5$\pm$121.6 days). In addition to routine laboratory and staging procedures, serum VEGF, b-FGF levels and platelet counts were determined as antiangiogenic markers. The antiangiogenic effects of HAD were evaluated by analyzing the differences between the values of the antiangiogenic markers before and after the treatment with HAD. Results: Serum b-FGF concentrations were significantly reduced after the treatment with HAD (P=0.042). Serum VEGF concentrations were found to have a somewhat decreasing change, though the change was not statistically significant (P=0.229). Platelet counts had little changes (P=O.80). Conclusions: It is supposed that HAD has effects on decreasing the serum b-FGF levels related with the clinical outcome of breast cancer patients.
Tyrosine Hydroxylase 유전자가 주입된 인간 배아줄기세포의 체외 신경세포 분화
신현아,김은영,이금실,조황윤,김용식,이원돈,박세필,임진호,Shin, Hyun-Ah,Kim, Eun-Young,Lee, Keum-Sil,Cho, Hwang-Yoon,Kim, Yong-Sik,Lee, Won-Don,Park, Se-Pill,Lim, Jin-Ho 대한생식의학회 2004 Clinical and Experimental Reproductive Medicine Vol.31 No.1
Objective: This study was to examine in vitro neural cell differentiation pattern of the genetically modified human embryonic stem cells expressing tyrosine hydroxylase (TH). Materials and Methods: Human embryonic stem (hES, MB03) cell was transfected with cDNAs cording for TH. Successful transfection was confirmed by western immunoblotting. Newly transfected cell line (TH#2/MB03) was induced to differentiate by two neurogenic factors retinoic acid (RA) and b-FGF. Exp. I) Upon differentiation using RA, embryoid bodies (EB, for 4 days) derived from TH#2/MB03 cells were exposed to RA ($10^{-6}M$)/AA ($5{\times}10^{-2}mM$) for 4 days, and were allowed to differentiate in N2 medium for 7, 14 or 21 days. Exp. II) When b-FGF was used, neuronal precursor cells were expanded at the presence of b-FGF (10 ng/ml) for 6 days followed by a final differentiation in N2 medium for 7, 14 or 21 days. Neuron differentiation was examined by indirect immunocytochemistry using neuron markers (NF160 & NF200). Results: After 7 days in N2 medium, approximately 80% and 20% of the RA or b-FGF induced Th#2/MB03 cells were immunoreactive to anti-NF160 and anti-NF200 antibodies, respectively. As differentiation continued, NF200 in RA treated cells significantly increased to 73.0% on 14 days compared to that in b-FGF treated cells (53.0%, p<0.05), while the proportion of cells expressing NF160 was similarly decreased between two groups. However, throughout the differentiation, expression of TH was maintained ($\sim$90%). HPLC analyses indicated the increased levels of L-DOPA in RA treated genetically modified hES cells with longer differentiation time. Conclusion: These results suggested that a genetically modified hES cells (TH#2/MB03) could be efficiently differentiated in vitro into mature neurons by RA induction method.
The Effects of Gamisipjeon-tang on the Skin Regeneration of Deep Second Degree Burns in Mice
Yu, Hyun-Jung,Hong, Seung-Ug The Society of Korean Medicine 2010 대한한의학회지 Vol.31 No.3
Objective: This study aimed to ascertain the curative effects of Gamisipjeon-tang (GST) used for wound healing on the skin regeneration of deep second degree burns in mice. Material & Methods: In vitro, the $I{\kappa}B$ kinase (IKK) mRNA expression, inducible nitric oxide synthase (iNOS) mRNA expression, and cyclooxygenase-2 (COX-2) mRNA expression in the GST concentration from 1 mg/$m{\ell}$ to 10 mg/$m{\ell}$ were measured. In vivo, the mice were divided into four groups : the normal group, the BE group (burn-elicited group, control group), the DC group (Duoderm CGF-treated group after burn elicitation), and the GST group (Gamisipjeon-tang treated group after burn elicitation). To determine the anti-inflammatory effects, nuclear factor (NF)-${\kappa}B$ p65, iNOS, COX-2 positive reaction were measured by immunohistochemistry. To estimate the skin regenerative effects, change of burn area, 5-bromo-2'-deoxyuridine (BrdU), and fibroblast growth factor (FGF) positive reaction were analyzed. Results: In vitro, the iNOS, IKK, COX-2 mRNA expression decreased according to the increase of GST concentration. The significant decrease of COX-2, iNOS, NF-${\kappa}B$ positive reaction were the highest in the GST group, followed by the DC group and the BE group (p<0.05). The diameter of burn area was significantly decreased in the GST group as compared to that in the DC and BE group (p<0.05). The BrdU and FGF positive reaction increased more significantly in the GST group than in the DC group, and more significantly in the DC group than in the BE group on the 3rd and 7th day after burn (p<0.05). FGF positive reaction increased in the BE and DC group, whereas it decreased significantly in the GST group on the 14th day (p<0.05). The BrdU positive reaction increased in the BE group, whereas it decreased significantly in the DC and GST group on the 14th day (p<0.05). Conclusions: This study shows that GST could decrease the inflammatory response and accelerate the skin regeneration as compared to the duoderm CGF in mice with deep second degree burns.
Lee Keum-Sil,Shin Hyun-Ah,Cho Hwang-Yoon,Kim Eun-Young,Lee Young-Jae,Wang Kyu-Chang,Kim Yong-Sik,Lee Hoon-Taek,Chung Kil-Saeng 한국발생생물학회 2003 한국발생생물학회 학술발표대회 Vol.2003 No.1
Embryonic stem (ES) cells proliferate extensively in the undifferentiated state and have the potential to differentiate into a variety of cell types in response to various environmental cues. The generation of functional dopaminergic neurons from ES cells is promising for cell replacement therapy to treat Parkinson's disease. We compared the in vitro differentiation potential of pluripotent human embryonic stem (hES, MB03) cells induced with basic fibroblast growth factor (bFGF) or retinoic acid (RA). Both types of treatment resulted in similar neural cell differentiation patterns at the terminal differentiation stage, specifically, 75% neurons and 11% glial cells. Additionally, treatment of hES cells with brain derived neurotrophic factor (BDNF) or transforming growth factor (TGF)- during the terminal differentiation stage led to significantly increased tyrosine hydroxylase (TH) expression, compared to control (P<0.05). In contrast, no effect was observed on the rate of mature or glutamic acid decarboxylase-positive neurons. Immunostaining and HPLC analyses revealed the higher levels of TH (20.3%) and dopamine in bFGF and TGF- treated hES cells than in RA or BDNF treated hES cells. The results indicate that TGF- may be successfully used in the bFGF induction protocol to yield higher numbers of functional dopaminergic neurons from hES cells.