• Journal of Animal Science and Technology
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• v.52 no.6
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• pp.521-527
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• 2010

Fibroblast growth factor receptor 1 (FGFR1) plays roles in angiogenesis, wound healing, and embryonic development via the regulation of cell proliferation, differentiation, and survival. It is well known that ectopic expression of FGFR1 is associated with cancer development. To characterize the function of FGFR1 in the normal and cancer cell lines DF-1 and DT40, respectively, we performed FGFR1 knockdown by RNA interference. In the DT40 cells, FGFR1 knockdown induced upregulation of FGFR2 and FGFR3 expression, downregulation of pro-apoptosis-related genes, and upregulation of anti-apoptosis-related genes. However, in DF-1 cells, FGFR1 knockdown induced upregulation of pro-apoptosis-related genes and downregulation of anti-apoptosis-related genes. Our data suggest that repression of FGFR1 induced upregulation of other FGF receptors and anti-apoptosis-related genes in cancer cells and pro-apoptosis-related genes in normal cells.

• Journal of Korean Neurosurgical Society
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• v.52 no.1
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• pp.7-13
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• 2012

Objective : The aim of this study was to determine whether single nucleotide polymorphisms (SNPs) of fibroblast growth factor (FGF) 2 gene and fibroblast growth factor receptor (FGFR) genes are associated with ossification of the posterior longitudinal ligament (OPLL). Methods : A total of 157 patients with OPLL and 222 controls were recruited for a case control association study investigating the relationship between SNPs of FGF2, FGFR1, FGFR2 and OPLL. To identify the association among polymorphisms of FGF2 gene, FGFR1, FGFR2 genes and OPLL, the authors genotyped 9 SNPs of the genes (FGF2 : rs1476217, rs308395, rs308397, and rs3747676; FGFR1 : rs13317 and rs2467531; FGFR2 : rs755793, rs1047100, and rs3135831) using direct sequencing method. SNPs data were analyzed using the SNPStats, SNPAnalyzer, Haploview, and Helixtree programs. Results : Of the SNPs, a SNP (rs13317) in FGFR1 was significantly associated with the susceptibility of OPLL in the codominant (odds ratio=1.35, 95% confidence interval=1.01-1.81, p=0.048) and recessive model (odds ratio=2.00, 95% confidence interval=1.11-3.59, p=0.020). The analysis adjusted for associated condition showed that the SNP of rs1476217 (p=0.03), rs3747676 (p=0.01) polymorphisms in the FGF2 were associated with diffuse idiopathic skeletal hyperostosis (DISH) and rs1476217 (p=0.01) in the FGF2 was associated with ossification of the ligament flavum (OLF). Conclusion : The results of the present study revealed that an FGFR1 SNP was significantly associated with OPLL and that a SNP in FGF2 was associated with conditions that were comorbid with OPLL (DISH and OLF).

• Journal of the korean academy of Pediatric Dentistry
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• v.26 no.4
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• pp.652-663
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• 1999

Craniosynostosis, the premature fusion of cranial sutures, presumably involves disturbance of the interactions between different tissues within the cranial sutures. Interestingly, point mutaions in the genes encoding for the fibroblast growth factor receptors(FGFRs), especially FGFR2, cause various types of human craniosynostosis syndromes. To elucidate the function of these genes in the early morphogenesis of mouse cranial sutures, we first analyzed by in situ hybridization the expression of FGFR2(BEK) and osteopontin, an early marker of osteogenic differentiation, in the sagittal suture of calvaria during embryonic(E15-E18) and postnatal stage(P1-P3). FGFR2(BEK) was intensely expressed in the osteogenic fronts, whose cells undergo differentiation into osteoprogenitor cells that ultimately lay down the bone matrix. Osteopontin was expressed throughout the parietal bones excluding the osteogenic fronts, the periphery of the parietal bones. To further examine the role of FGF-mediated FGFR signaling in cranial suture, we did in vitro experiments in E15.5 mouse calvarial explants. Interestingly, implantation of FGF2 soaked beads onto both the osteogenic fronts and mid-mesenchyme of sagittal suture after 36 hours organ culture resulted in the increase of the tissue thickness and cell number around FGF2 beads, moreover FGF4-soaked beads implanted onto the osteogenic fronts stimulated suture closure due to an accelerated bone growth, compared to FGF4 beads placed onto mid-mesenchyme of sagittal suture and BSA control beads. In addition FGF2 induced the ectopic expression of osteopontin and Msx1 genes. Taken together, these data indicate that FGF-mediated FGFR signaling has a important role in regulating the cranial bone growth and maintenance of cranial suture, and suggest that FGF-mediated FGFR signaling is involved in regulating the balance between the cell proliferation and differentiation through inducing the expression of osteopontin and Msx1 genes.

• The korean journal of orthodontics
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• v.36 no.4
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• pp.284-294
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• 2006

Objective: Activating mutations in the fibroblast growth factor receptor-2 (FGFR2) have been shown to cause syndromic craniosynostosis such as Apert and Crouzon syndromes. The purpose of this pilot study was to investigate the resultant phenotypes induced by the two distinctive bone-targeted gene constructs of FGFR2, Pro253Arg and Cys278Phe, corresponding to human Apert and Crouzon syndromes respectively. Methods: Wild type and a transgenic mouse model with normal FGFR2 were used as controls to examine the validity of the microinjection. Micro-CT and morphometric analysis on the skull revealed the following results. Results: Both Apert and Crouzon mutants of FGFR2 induced fusion of calvarial sutures and anteroposteriorly constricted facial dimension, with anterior crossbite present only in Apert mice. Apert mice differed from Crouzon mice and transgenic mice with normal FGFR2 in the anterior cranial base flexure and calvarial flexure angle which implies a possible difference in the pathogenesis of the two mutations. In contrast, the transgenic mice with normal FGFR2 displayed normal craniofacial phenotype. Conclusion: Apert and Crouzon mutations appear to lead to genotype-specific phenotypes, possibly causing the distinctive sites and sequence of synostosis in the calvaria and cranial base. The exact function of the altered FGFR2 at each suture needs further investigation.

• Food Science of Animal Resources
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• v.43 no.6
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• pp.1017-1030
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• 2023

Fetal bovine serum (FBS), which contains various nutrients, comprises 20% of the growth medium for cell-cultivated meat. However, ethical, cost, and scientific issues, necesitates identification of alternatives. In this study, we investigated commercially manufactured serum-free media capable of culturing Hanwoo satellite cells (HWSCs) to identify constituent proliferation enhancing factors. Six different serum-free media were selected, and the HWSC proliferation rates in these serum-free media were compared with that of control medium supplemented with 20% FBS. Among the six media, cell proliferation rates were higher only in StemFlex^TM Medium (SF) and Mesenchymal Stem Cell Growth Medium DXF (MS) than in the control medium. SF and MS contain high fibroblast growth factor 2 (FGF2) concentrations, and we found upregulated FGF2 protein expression in cells cultured in SF or MS. Activation of the fibroblast growth factor receptor 1 (FGFR1)-mediated signaling pathway and stimulation of muscle satellite cell proliferation-related factors were confirmed by the presence of related biomarkers (FGFR1, FRS2, Raf1, ERK, p38, Pax7, and MyoD) as indicated by quantitative polymerase chain reaction, western blotting, and immunocytochemistry. Moreover, PD173074, an FGFR1 inhibitor suppressed cell proliferation in SF and MS and downregulated related biomarkers (FGFR1, FRS2, Raf1, and ERK). The promotion of cell proliferation in SF and MS was therefore attributed to FGF2, which indicates that FGFR1 activation in muscle satellite cells may be a target for improving the efficiency of cell-cultivated meat production.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.6
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• pp.2787-2793
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• 2016

Background: Urinary bladder cancer is a common malignancy in the West and ranks as the $7^{th}$ most common cancer in our region of Kashmir, India. FGFR3 mutations are frequent in superficial urothelial carcinoma (UC) differing from the RAS gene mutational pattern. The aim of this study was to analyze the frequency and association of FGFR3 and RAS gene mutations in UC cases. Materials and Methods: Paired tumor and adjacent normal tissue specimens of 65 consecutive UC patients were examined. DNA preparations were evaluated for the occurrence of FGFR3 and RAS gene mutations by PCR-SCCP and DNA sequencing. Results: Somatic point mutations of FGFR3 were identified in 32.3% (21 of 65). The pattern and distribution were significantly associated with low grade/stage (p<0.05). The overall mutations in exon 1 and 2 in all the forms of RAS genes aggregated to 21.5% and showed no association with any clinic-pathological parameters. In total, 53.8% (35 of 65) of the tumors studied had mutations in either a RAS or FGFR3 gene, but these were totally mutually exclusive in and none of the samples showed both the mutational events in mutually exclusive RAS and FGFR3. Conclusions: We conclude that RAS and FGFR3 mutations in UC are mutually exclusive and non-overlapping events which reflect activation of oncogenic pathways through different elements.

• Clinical and Experimental Pediatrics
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• v.53 no.7
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• pp.774-777
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• 2010

Pfeiffer syndrome is a rare autosomal dominant disorder characterized by coronal craniosynostosis, brachycephaly, mid-facial hypoplasia, and broad and deviated thumbs and great toes. Pfeiffer syndrome occurs in approximately 1:100,000 live births. Clinical manifestations and molecular genetic testing are important to confirm the diagnosis. Mutations of the fibroblast growth factor receptor 1 ($FGFR1$) gene or $FGFR2$ gene can cause Pfeiffer syndrome. Here, we describe a case of Pfeiffer syndrome with a novel c833_834GC>TG mutation (encoding Cys278Leu) in the $FGFR2$ gene associated with a coccygeal anomaly, which is rare in Pfeiffer syndrome.

• Journal of Korean Neurosurgical Society
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• v.59 no.3
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• pp.187-191
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• 2016

Craniosynostosis is defined as the premature fusion of one or more of the cranial sutures. It leads not only to secondary distortion of skull shape but to various complications including neurologic, ophthalmic and respiratory dysfunction. Craniosynostosis is very heterogeneous in terms of its causes, presentation, and management. Both environmental factors and genetic factors are associated with development of craniosynostosis. Nonsyndromic craniosynostosis accounts for more than 70% of all cases. Syndromic craniosynostosis with a certain genetic cause is more likely to involve multiple sutures or bilateral coronal sutures. FGFR2, FGFR3, FGFR1, TWIST1 and EFNB1 genes are major causative genes of genetic syndromes associated with craniosynostosis. Although most of syndromic craniosynostosis show autosomal dominant inheritance, approximately half of patients are de novo cases. Apert syndrome, Pfeiffer syndrome, Crouzon syndrome, and Antley-Bixler syndrome are related to mutations in FGFR family (especially in FGFR2), and mutations in FGFRs can be overlapped between different syndromes. Saethre-Chotzen syndrome, Muenke syndrome, and craniofrontonasal syndrome are representative disorders showing isolated coronal suture involvement. Compared to the other types of craniosynostosis, single gene mutations can be more frequently detected, in one-third of coronal synostosis patients. Molecular diagnosis can be helpful to provide adequate genetic counseling and guidance for patients with syndromic craniosynostosis.

• Journal of Integrative Natural Science
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• v.10 no.2
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• pp.85-94
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• 2017

Fibroblast growth factor receptor (FGFR) belongs to the family of receptor tyrosine kinase. They play important roles in cell proliferation, differentiation, development, migration, survival, wound healing, haematopoiesis and tumorigenesis. FGFRs are reported to cause several types of cancers in humans which make it an important drug target. In the current study, HQSAR analysis was performed on a series of recently reported 1H-Pyrazolo [3,4-b]pyridine derivatives as FGFR antagonists. The model was developed with Atom (A) and bond (B) connection (C), chirality (Ch), hydrogen (H) and donor/acceptor (DA) parameters and with different set of atom counts to improve the model. A reasonable HQSAR model ($q^2=0.701$, SDEP=0.654, NOC=5, $r^2=0.926$, SEE=0.325, BHL=71) was generated which showed good predictive ability. The contribution map depicted the atom contribution in inhibitory effect. A contribution map for the most active compound (compound 24) indicated that hydrogen and nitrogen atoms in the side chains of ring B as well as hydrogen atoms in the side chain of ring C and the nitrogen atom in the ring D contributed positively to the activity in inhibitory effect whereas, the lowest active compound (compound 04) showed negative contribution to inhibitory effect. Thus results of our study can provide insights in the designing potent and selective FGFR kinase inhibitors.

• Journal of Genetic Medicine
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• v.7 no.2
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• pp.151-155
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• 2010

Apert syndrome is a rare congenital anomaly characterized by craniofacial malformations and severe symmetrical syndactyly of fingers and toes. This syndrome is caused by a genetic mutation; the S253 mutation is common, though the P253R mutation is not as frequent. Common symptoms include skeletal malformations, poor joint mobility, eye and ear problems, cleft palate, and orthodontic and other dental problems. We report a case of an infant with the common morphological features of Apert syndrome. Interestingly, she was found to have the P253R mutation in FGFR2 exon VIII, which has been less commonly observed in Korea. A brief review of the literature is included.