• Biodesign
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• 제6권4호
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• pp.92-95
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• 2018

API5 is a unique oncogenic, non-BIR type IAP nuclear protein and is up-regulated in several cancers. It exerts several functions, such as apoptosis inhibition, cell cycle progression, cancer immune escape, and anticancer drug resistance. Although structural studies of API have revealed that API5 mediates protein-protein interactions, its detailed molecular functions remain unknown. Since FGF2 is one of API5's major interacting proteins, structural studies of the API5-FGF2 complex will provide insight into both proteins' molecular function. We overexpressed and purified API5 and FGF2 in Escherichia coli and crystallized the API-FGF2 complex using polyethylene glycol (PEG) 6000 as a precipitant. Diffraction data were collected to a $2.7{\AA}$ resolution using synchrotron X-rays. Preliminary diffraction analysis revealed that the API5-FGF2 complex crystal belongs to the space group $P2_12_12_1$ with the following unit cell parameters: a = 46.862, b = 76.523, $c=208.161{\AA}$. One asymmetric unit with 49.9% solvent contains one API5-FGF2 complex. Molecular replacement calculation, using API5 and FGF2 coordinates, provided a clear electron density map for an API5-FGF2 complex.

• Bulletin of the Korean Chemical Society
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• 제28권9호
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• pp.1613-1614
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• 2007

• Clinical and Experimental Reproductive Medicine
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• 제24권3호
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• pp.355-359
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• 1997

Leiomyomas, which are the commonest pelvic tumors in women, are originated from myometrial cells. Although the exact initial pathophysiologic event of the leiomyoma is not known, recent evidences suggested that the effects of sex steroid hormones in the process of tumor growth are mediated by local production of growth factors including epidermal growth factor (EGF), insulin-like growth factor-I (IGF-I) and insulin-like growth factor-II (IGF-II). If we look at the effects of other cytokines, it was suggested that basic fibroblast growth factor (bFGF) may stimulate the proliferation of myometrial and leiomyomas cells. And it was reported that interferon-${\alpha}$ inhibit the action of bFGF. Therefore, we examined the effect of bFGF and interferon-${\alpha}$ on the proliferation of leiomyoma and myometrial cells. bFGF stimulated the myometrial and leiomyoma cells significantly at the concentration of 1ng/ml (p<0.05) and 5ng/ml (p<0.05). However, Interferon-${\alpha}$ inhibited the cell proliferation of myometrial and leiomyoma cells significantly at the concentration of 100U/ml (p<0.05) and 1000U/ml (p<0.05). And the stimulated effects of bFGF with the various concentration on the myometrial and leiomyoma cells ware inhibited by interferon-${\alpha}$ with 100U/ml. Therefore, we concluded that bFGF may stimulate the myometrial and leiomyoma cell proliferation and interferon-${\alpha}$ may inhibit the myometrial and leiomyoma cell proliferation through blocking the effect of basic fibroblast growth factor.

• 대한한의학회지
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• 제26권4호
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• pp.22-30
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• 2005

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.

• 한국생물공학회:학술대회논문집
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• 한국생물공학회 2000년도 추계학술발표대회 및 bio-venture fair
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• pp.429-432
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• 2000

생체 적합성, 생분해성, 항균성 등의 특징을 갖는 키토산 지지체는 type I -p collagen과 bFGF 또는 fibronectin을 함께 코팅함으로써 세포적합성을 향상시켜 섬유아세포의 증식과 ECM의 분비를 증가시킬 수 있으며, 인공피부를 위한 적합한 지지체로 사용될 수 있다고 사료된다.

• Molecules and Cells
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• 제28권1호
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• pp.13-17
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• 2009

Basic fibroblast growth factor (bFGF) plays an important role in angiogenesis. However, the underlying mechanisms are not clear. $Mg^{2+}$ is the most abundant intracellular divalent cation in the body and plays critical roles in many cell functions. We investigated the effect of bFGF on the intracellular $Mg^{2+}$ concentration ($[Mg^{2+}]_i$) in human umbilical vein endothelial cells (HUVECs). bFGF increased ($[Mg^{2+}]_i$) in a dose-dependent manner, independent of extracellular $Mg^{2+}$. This bFGF-induced $[Mg^{2+}]_i$ increase was blocked by tyrosine kinase inhibitors (tyrphostin A-23 and genistein), phosphatidylinositol 3-kinase (PI3K) inhibitors (wortmannin and LY294002) and a phospholipase $C{\gamma}$ ($PLC{\gamma}$) inhibitor (U73122). In contrast, mitogen-activated protein kinase inhibitors (SB202190 and PD98059) did not affect the bFGF-induced $[Mg^{2+}]_i$ increase. These results suggest that bFGF increases the $[Mg^{2+}]_i$ from the intracellular $Mg^{2+}$ stores through the tyrosine kinase/PI3K/$PLC{\gamma}$-dependent signaling pathways.

• Clinical and Experimental Reproductive Medicine
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• 제31권1호
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• pp.19-27
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• 2004

Objective: This study was to examine the in vitro neural cell differentiation patterns of human embryonic stem (hES) cells following treatment of various neurotrophic factors [basic fibroblast growth factor (bFGF), retinoic acid (RA), brain derived neurotrophic factor (BDNF) and transforming growth factor (TGF)-$\alpha$], particulary in dopaminergic neuron formation. Methods: The hES cells were induced to differentiate by bFGF and RA. Group I) In bFGF induction method, embryoid bodies (EBs, for 4 days) derived from hES were plated onto gelatin dish, selected for 8 days in ITSFn medium and expanded at the presence of bFGF (10 ng/ml) for another 6 days followed by a final differentiation in N2 medium for 7, 14 and 21 days. Group II) For RA induction, EBs were exposed of RA ($10^{-6}M$) for 4 days and allowed to differentiate in N2 medium for 7, 14 and 21 days. Group III) To examine the effects of additional neurotrophic factors, bFGF or RA induced cells were exposed to either BDNF (10 ng/ml) or TGF-$\alpha$ (10 ng/ml) during the 21 days of final differentiation. Neuron differentiation and dopamine secretion were examined by indirect immunocytochemistry and HPLC, respectively. Results: The bFGF or RA treated hES cells were 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 BDNF or TGF-$\alpha$ during the terminal differentiation stage led to significantly increased tyrosine hydroxylase (TH) expression of a dopaminergic neuron marker, compared to control (p<0.05). In contrast, no effect was observed on the rate of mature neuron (NF-200) or glutamic acid decarboxylase-positive neurons. Immunocytochemistry and HPLC analyses revealed the higher levels of TH expression (20.3%) and dopamine secretion (265.5 $\pm$ 62.8 pmol/mg) in bFGF and TGF-sequentially treated hES cells than those in $\alpha$ RA or BDNF treated hES cells. Conclusion: These results indicate that the generation of dopamine secretory neurons from in vitro differentiated hES cells can be improved by TGF-$\alpha$ addition in the bFGF induction protocol.

• Clinical and Experimental Reproductive Medicine
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• 제34권4호
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• pp.239-252
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• 2007

목 적: 사람의 HAD와 HUC를 심근세포로 분화 유도하고자 하였다. 연구방법: 사람의 HAD와 HUC를 분리하여 5-azacytidine을 24시간 처리하고 여러 가지 BMP와 FGF을 첨가하여 배양하였다. 또한 HUC은 BMP와 FGF와 함께 activin A 또는 TGF-$\beta$1 또는 Wnt inhibitor를 첨가하여 배양한 후 심근세포 특이 유전자의 발현을 조사하였다. 결 과: HAD를 5-azacytidine 처리하고 기본배양액에서 4주 동안 배양하였을 때 TnT 유전자가 새로이 발현하였으며 Cmlc1과 kv4.3의 발현 양이 증가하였다. 5-azacytidine 처리 후에 BMP-4와 함께 FGF-4 (B4/F4) 또는 FGF-8 (B4/F8)을 첨가하여 배양하였을 때는 $\beta$-MHC 유전자 발현이 새로이 유도되었으며, Cmlc1, TnT, TnI 그리고 Kv4.3 유전자 발현 양이 더 많이 증가하였다. HUC은 5-azacytidine 및 BMP와 FGF 처리에 의해 유전자 발현 변화가 없었다. 그러나 BMP와 FGF와 함께 activin A 또는 TGF-$\beta$1을 첨가하여 배양하였을 때, BMP-2와 FGF-8 (B2/F8)을 첨가하여 배양한 세포에서 $\beta$-MHC 발현이 새로이 유도되었으며 $\alpha$-CA, TnT 그리고 Kv4.3 유전자의 발현이 증가하였다. 또한 BMP와 FGF와 함께 Wnt inhibitor를 처리하여 1주 동안 배양하였을 때 Cinlc1 유전자 발현이 새로이 유도되었으며 $\alpah$-CA, TnT, TnI 그리고 Kv4.3의 발현이 증가되었다. 결 론: HAD는 BMP와 FGF 처리에 의해 심근세포 특이 유전자의 발현증가를 유도할 수 있었으며 HUC는 BMP와 FGF와 함께 activin A 또는 TGF-$\beta$1 또는 Wnt inhibitor를 처리함으로써 심근세포 특이 유전자의 발현증가를 유도할 수 있었다. 따라서 HAD와 HUC는 심장질환 치료를 목적으로 하는 세포 치료에 이용될 수 있을 것으로 사료된다.

• BMB Reports
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• 제46권12호
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• pp.617-622
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• 2013

Rac1 plays a key role in neurite outgrowth via reorganization of the actin cytoskeleton. The molecular mechanisms underlying Rac1-mediated actin dynamics in the cytosol and plasma membrane have been intensively studied, but the nuclear function of Rac1 in neurite outgrowth has not yet been addressed. Using subcellular fractionation and immunocytochemistry, we sought to explore the role of nuclear Rac1 in neurite outgrowth. bFGF, a strong agonist for neurite outgrowth in PC12 cells, stimulated the nuclear accumulation of an active form of Rac1. Rac1-PBR (Q) mutant, in which six basic residues in the polybasic region at the C-terminus were replaced by glutamine, didn't accumulate in the nucleus. In comparison with control cells, cells expressing this mutant form of Rac1 displayed a marked defect in extending neurites that was concomitant with reduced expression of MAP2 and MEK-1. These results suggest that Rac1 translocation to the nucleus functionally correlates with bFGF-induced neurite outgrowth.

• Plant Resources
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• 제8권3호
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• pp.209-216
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• 2005

Persicaria thunbergii has been utilized for the treatment of cancer as a folk medicine. We examined the effect of isorhamnetin, a flavonoid isolated from Persicaria thunbergii, on angiogenesis in vitro and in vivo. Basic fibroblast growth factor (bFGF) is a potent angiogenic factor found in various tumors. In this study, we found that the isorhamnetin decreased bFGF-induced human umbilical vein endothelial cells (HUVECs) proliferation and migration in a concentration-dependent manner (5, 10 and $20\;{\mu}M$) whereas, it did not inhibit bFGF-induced capillary-like formation of HUVECs. The chicken chorioallantoic membrane assay revealed that addition of isorhamnetin (10, 20 and $40\;{\mu}M$) displayed an antiangiogenic effect in vivo. These results suggest that the isorhamnetin inhibits the proliferation and migration of endothelial cells induced by bFGF, which may explain its anti-angiogenic properties.