OBJECTIVETo improve the understanding of patients with 8p11 myeloproliferative syndrome (EMS) harboring ins(13;8)(q12;p11p23)/ZNF198 -FGFR1.

METHODSWe reported here a 8p11 EMS case and provided more details on the clinical and molecular features of ins(13;8)(q12;p11p23)/ZNF198-FGFR1，full length ZNF198-FGFR1 was cloned by overlap extension PCR method，and the literatures on this topic were reviewed.

RESULTSClinically, the case with ins(13;8)(q12;p11p23)/ZNF198-FGFR1 had distinct hematological and clinical characteristics: hyperleukocytosis, myeloid hyperplasia，widespread adenopathy and lymphoma; Fluorescence in situ hybridization (FISH) disclosed the positive FGFR1 gene rearrangement; Further molecular studies confirmed a mRNA in-frame fusion between exon 17 of the ZNF198 gene and exon 9 of FGFR1 gene ，the full length ZNF198-FGFR1 was composed of a NH2 terminus of ZNF198 including the ZNF and proline-rich domains, whereas the COOH terminus of FGFR1 included 2 tyrosine kinase domains.

CONCLUSIONEMS with ins(13;8)(q12;p11p23)/ZNF198 -FGFR1 was a very rare， distinct myeloproliferative neoplasm, the fusion gene and chimeric protein with constitutive activation of the FGFR1 tyrosine kinase.

Chromosomes, Human, Pair 13 ; Chromosomes, Human, Pair 8 ; DNA-Binding Proteins ; Exons ; Humans ; In Situ Hybridization, Fluorescence ; Myeloproliferative Disorders ; Receptor, Fibroblast Growth Factor, Type 1 ; Receptors, Fibroblast Growth Factor ; Transcription Factors ; Translocation, Genetic

PURPOSE: Few cells with stem cell characteristics possess capabilities of self-renewal and differentiation, which leads to high tumorigenesis and resistance to standard chemotherapeutic agents. These cells are mostly quiescent, and arrest occurs at the mitotic G0/G1 phase in mitosis. We explored the effects of basic fibroblast growth factor (bFGF) on the MCF-7 cell cycle with CD44+/CD24-. METHODS: Cancer-initiating cells were propagated as mammospheres. The CD44+/CD24- subpopulation was sorted by a fluorescence activating cell sorter-Vantage flow cytometer. A cell cycle analysis was performed with different bFGF concentrations. RESULTS: Differences in the CD44+/CD24- cell proliferation under different bFGF concentrations were observed (p=0.001). When the bFGF concentration was increased, the proportion of CD44+/CD24- at G0/G1 decreased (p=0.023). CONCLUSION: We conclude that bFGF may sustain CD44+/CD24- cell proliferation and could promote cell progression through the G0/G1-->G2/S phase transition.
Breast Neoplasms ; Cell Cycle ; Cell Proliferation ; Cell Transformation, Neoplastic ; Fibroblast Growth Factor 2 ; Fibroblast Growth Factors ; Fluorescence ; MCF-7 Cells ; Mitosis ; Phase Transition ; Stem Cells

BACKGROUND: A growth factor cocktail (GFC) including fibroblast growth factor 9 (FGF9) in combination with microneedling is an effective and safe treatment for patients with androgenetic alopecia (AGA). However, there is a lack of studies evaluating its effects based on microneedle depth. OBJECTIVE: This study aimed to evaluate the effects of a GFC including FGF9 on hair growth in patients with AGA, and compare the differences in efficacy according to microneedle depth. METHODS: The study was performed on patients with AGA who were treated with topical GFC including FGF9 with microneedling once every 2 weeks for 3 months. The scalp was divided into right and left sides, and treated with GFC including FGF9 (right side) and normal saline (left side). The microneedle depth was 0.8 mm for both sides. A total of 22 patients (11 males and 11 females) were enrolled. GFC including FGF9 was topically applied with a microneedle medical device. Treatment efficacy was evaluated through phototrichogram and digital photograph analyses after 6 repeated treatments for 3 months. RESULTS: The phototrichogram images showed that 3 months of treatment with GFC including FGF9 with microneedling increased hair density (27.4±4.4/cm²) and diameter (2.7±2.7 µm); increases in hair density (5.7±4.4/cm²) and diameter (2.2±2.3 µm) were also seen in the region of the scalp that received normal saline. These results were statistically significant (p < 0.05). The treatment effect was not significantly different between microneedle depths of 0.8 mm (used in this study) and 0.5 mm (used in our previous study) in terms of both hair density and hair diameter. CONCLUSION: GFC including FGF9 with microneedling is an effective and safe treatment for patients with AGA. According to the results of this study and our previous report, we believe that microneedle depths of 0.5∼0.8 mm can sufficiently stimulate the scalp to increase drug-delivery.
Alopecia ; Fibroblast Growth Factor 9* ; Fibroblast Growth Factors* ; Fibroblasts* ; Hair* ; Humans ; Male ; Scalp ; Therapeutic Uses* ; Treatment Outcome

OBJECTIVETo investigate the effect of topical propranolol gel on the levels of plasma vascular endothelial growth factor (VEGF), basic fibroblastic growth factor (bFGF) and matrix metalloproteinases-9 (MMP-9) in proliferating infantile hemangiomas (IHs) of superficial type.

METHODS33 consecutive children with superficial IHs were observed pre-treatment, 1 and 3 months after application of topical propranolol gel for the levels of plasma VEGF, MMP-9 and bFGF by enzyme-linked immunosorbent assay (ELISA) in Department of General Surgery of Dongfang Hospital from February 2013 to February 2014. The plasma results of IHs were compared with those of 30 healthy infants. The clinical efficacy in IHs was evaluated by Achauer system. Differences of plasma results between the healthy group and the IHs group pre-treatment were analyzed using Mann-Whitney U-test. Paired sample comparisons of any two time points of pre-treatment, 1 month and 3 months after treatment in IHs were evaluated by Wilcoxon signed-rank test.

RESULTSThe clinical efficiency of topical propranolol gel at 1, 3 months after application were 45.45%, 81.82% respectively. The levels of plasma VEGF and MMP-9 in patients pre- treatment were higher than those in healthy infants [(362.16 ± 27.29) pg/ml vs (85.63 ± 8.14) pg/ml, (1376.41 ± 42.15) pg/ml vs (687.27 ± 44.1) pg/ml, P < 0.05], but the level of bFGF did not show significant difference [(176.03 ± 13.60 ) pg/ml vs (235.94 ± 35.43 ) pg/ml, P > 0. 05 ]. The concentrations of VEGF and bFGF at 1, 3 months after treatment decreased obviously [(271.51 ± 18.59) pg/ml vs (362.16 ± 27.29 ) pg/ml, (135.85 ± 12.66) pg/ml vs (176.03 ± 13.60) pg/ml], 1 month after treatment vs pre-treatment, P < 0.05; (240.80 ± 19.89) pg/ml vs (362.16 ± 27.29) pg/ml, (107.31 ± 5.82) pg/ml vs (176.03 ± 13.60) pg/ml, 3 month after treatment vs pre-treatment, P < 0.05, whereas the levels of plasma MMP-9 declined slightly [(1321.18 ± 48.74) pg/ml vs (1376.41 ± 42.15 ) pg/ml, (1468.68 ± 32.78) pg/ml vs (1376.41 ± 42 2.15 ) pg/ml, P > 0.05 ].

CONCLUSIONSPropranolol gel may suppress the proliferation of superficial infantile bemangiomas by reducing VEGF and bFGF.

Administration, Topical ; Case-Control Studies ; Child ; Enzyme-Linked Immunosorbent Assay ; Fibroblast Growth Factor 2 ; blood ; Gels ; Hemangioma ; blood ; drug therapy ; Humans ; Infant ; Matrix Metalloproteinase 9 ; blood ; Propranolol ; pharmacology ; Time Factors ; Vascular Endothelial Growth Factor A ; blood

OBJECTIVE: Supplementation with vitamin E is able to protect bone against free radical-induced elevation of bone-resorbing cytokines. We examined gene expression by microarray analysis during the differentiation of human mesenchymal stem cells treated with vitamin E into osteoblasts in vitro. METHODS: Human bone marrow stem cells were cultured in osteogenic differentiation medium and vitamin E was added. A colorimetric immunoassay for the quantification of cell proliferation was used to measure osteoblast differentiation. Gene expression was analyzed using a microarray technique. We also used a real time reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: It was found that vitamin E enhanced cell proliferation when compared to cells cultured in media without vitamin E. We focused on 68 genes which are related to osteogenesis and osteoclastogenesis. Alkaline phosphatase, transforming growth factor-beta 1, fibroblast growth factor receptor 1, matrix metalloproteinase 2, muscle segment homeobox 2, bone morphogenetic protein 1, biglycan, vascular endothelial growth factor B, dentin sialophosphoprotein, cartilage oligomeric matrix protein, runt-related transcription factor 2, fibroblast growth factor receptor 3, and SMAD2 were upregulated > 2-fold compared to the control. Conversely, osteopetrosis-associated transmembrane protein 1, microphthalmia-associated transcription factor, and epidermal growth factor receptor were downregulated > 2-fold compared to the control. Vitamin E produced a 1.5-fold increase in the expression of runt-related transcription factor 2 and transforming growth factor-beta 1 as determined by real time RT-PCR. CONCLUSION: Vitamin E had a positive effect on the gene expressions regarding osteogenic differentiation of mesenchymal stem cells.
Alkaline Phosphatase ; Biglycan ; Bone Marrow ; Bone Morphogenetic Protein 1 ; Cartilage ; Cell Proliferation ; Cytokines ; Dentin ; Durapatite ; Extracellular Matrix Proteins ; Gene Expression ; Genes, Homeobox ; Glycoproteins ; Humans ; Immunoassay ; Matrix Metalloproteinase 2 ; Mesenchymal Stromal Cells ; Microarray Analysis ; Microphthalmia-Associated Transcription Factor ; Muscles ; Osteoblasts ; Osteogenesis ; Phosphoproteins ; Receptor, Epidermal Growth Factor ; Receptor, Fibroblast Growth Factor, Type 1 ; Receptor, Fibroblast Growth Factor, Type 3 ; Sialoglycoproteins ; Stem Cells ; Transcription Factors ; Vascular Endothelial Growth Factor B ; Vitamin E ; Vitamins

Fibroblast growth factor(FGF) is a mitogen and a potent antigenic factor. It is also known as a differentiation factor for neuroectodermal-derived cell. It has been observed to be expressed in more than 90% of m-RNA of human meningiomas and gliomas. Progesterone receptor(PR) is well known surface receptor of meningioma and its number is greater than that of estrogen receptor. It is one os the known prognostic factors of meningioma. Meningiomas themselves are regarded as benign tumors in general, however some types show aggressive features. In the present study, authors examined the expression of FGF-1 and PR in meningioma tissues using immunohistochemical techniques with monoclonal antibody against human FGF-1 and PR. FGF-1 was detected in 25 of 35 classic meningiomas and in 7 of 9 aggressive ones. PR is expressed in 5 cases of classic and 2 cases of aggressive meningiomas. These results suggest FGF-1 may be involved in aggressive progression of meningioma. There was no significant difference of aggressiveness and expression of FGFR-1 and PR between classic and aggressive meningiomas, including their subtypes.
Estrogens ; Fibroblast Growth Factor 1 ; Fibroblast Growth Factors* ; Fibroblasts* ; Glioma ; Humans ; Meningioma* ; Progesterone*

OBJECTIVE: To determine the time course and potential mechanism of fibroblast growth factor-1 (FGF-1) in the regulation of adipogenesis.
 METHODS: We cultured human Simpson-Golabi-Behmel syndrome (SGBS) pre-adipocytes with recombinant FGF-1 and harvested cells at various stages prior to and during differentiation; at cell proliferation (D-3), confluence (D0), early (D3), middle (D7) and mature (D14) stages of differentiation. We determined lipid accumulation in mature adipocytes by morphological observation and quantitative measurement of oil red O staining. We also examined the expression of adipogenic genes and related markers involved in the Wnt/β-catenin pathway using quantitative Real-time PCR and Western blot.
 RESULTS: Compared to control SGBS cells, treatment with FGF-1 increased lipid accumulation; induced a sustained increase in the mRNA for peroxisome proliferater-activated receptor γ (PPARγ), glyceraldehyde-3-phosphate dehydrogenase (G3PDH), adiponectin and glucose transporter type 4 (GLUT4); and promoted a sustained decrease in expression of markers of the Wnt/β-catenin pathway, β-catenin and transcription factor 4 (TCF4).
 CONCLUSION The adipogenic effects of FGF-1 are apparent throughout the whole priming and differentiation period in human SGBS pre-adipocytes. Furthermore, our results suggest that FGF-1 
promotes adipogenesis, at least in part, via a sustained decrease in activity of the Wnt/β-catenin pathway.
Adipocytes ; drug effects ; metabolism ; Adipogenesis ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ; metabolism ; Cell Differentiation ; Cells, Cultured ; Fibroblast Growth Factor 1 ; pharmacology ; Humans ; Recombinant Proteins ; pharmacology ; Transcription Factor 4 ; Transcription Factors ; metabolism ; Wnt Signaling Pathway ; beta Catenin ; metabolism

OBJECTIVE: Recently, cultured myoblast transplantation has been extensively studied as a gene complementation approach in such genetic diseases as Duchenne muscular dystrophy (DMD). In the present work we investigated the stimulating effects of the growth factors, such as basic fibroblast growth factor (bFGF), leukemia inhibitory factor (LIF) and interleukin-1 (IL-1), on growth rate and differentiation of myoblast. METHOD: Human myoblasts were cultured from biopsy and treated in vitro with various concentration of bFGF, LIF and IL-1. In serum-free defined medium the following observation were made to evaluate differentiation. RESULTS: bFGF and LIF except IL-1 were found to have stimulating effect of myoblast proliferation comparing to control group (p<0.05), yet there were no statistically significant differences among each growth factors (p<0.05). The most significant growth stimulation of myoblasts in culture was achieved by adding 3.0 ng/ml of bFGF, producing a stimulation effect up to 2.01-fold. All myoblasts treated with growth factors differentiated into myotube. CONCLUSION: Our findings indicate that bFGF and LIF stimulate the proliferation of myoblast, which may result in an effective way in producing large numbers of myoblasts for clinical myoblast transplantation in DMD patients.
Biopsy ; Complement System Proteins ; Fibroblast Growth Factor 2 ; Fibroblast Growth Factors* ; Fibroblasts* ; Genes, vif ; Humans ; Intercellular Signaling Peptides and Proteins ; Interleukin-1* ; Leukemia Inhibitory Factor* ; Leukemia* ; Muscle Fibers, Skeletal ; Muscular Dystrophy, Duchenne ; Myoblasts*

The aim of this project is to establish a fibroblast growth factor-21 (FGF-21) signaling pathway targeted cell model, for screening a class of FGF-21 receptor agonists as anti-diabetic candidates. FGF-21 requires beta klotho transmembrane proteins as co-receptor for the activation of tyrosine kinase FGF receptor (FGFR) signaling, thereby activating a series of intracellular signaling pathways and regulating gene transcription for glucose metabolism. Firstly a recombinant plasmid expressing co-receptor beta klotho and EGFP reporter genes was constructed. After introducing the recombinant plasmid into package cells, the cell culture supernatant was used to infect 3T3-L1 cells, which were then screened for stably expressing beta klotho gene. Administration of FGF-21 increased the expression of GLUT1 and stimulated GLUT1-mediated glucose uptake. This novel cell model can be conveniently used in high-throughput drug screening of FGF-21 or FGF-21 analogues.
3T3-L1 Cells ; Animals ; Drug Evaluation, Preclinical ; Fibroblast Growth Factors ; metabolism ; pharmacology ; Glucose ; metabolism ; Glucose Transporter Type 1 ; genetics ; metabolism ; Glucose Transporter Type 4 ; genetics ; metabolism ; HEK293 Cells ; Humans ; Hypoglycemic Agents ; metabolism ; Membrane Proteins ; genetics ; metabolism ; Mice ; NIH 3T3 Cells ; Plasmids ; RNA, Messenger ; metabolism ; Receptors, Fibroblast Growth Factor ; agonists ; Recombinant Proteins ; genetics ; metabolism ; Retroviridae ; genetics ; Signal Transduction ; Transfection

OBJECTIVETo study the difference in the expression of VEGF, bFGF and their receptors between young and postmenopausal women with breast cancer.

METHODSThe expression of VEGF, FLK-1, bFGF and FLG in 40 young and 30 postmenopausal women with breast cancer was studied by immunohistochemical method (SABC), with its relation with axillary lymph node metastasis and the clinical and pathologic characteristics. The expression index between these two groups was compared.

RESULTSThe positive axillary lymph node rate and the mean expression of VEGF, bFGF in the young group were higher than postmenopausal group (P < 0.01 and P < 0.05), respectively. The mean expression of VEGF, bFGF, FLK-1 and FLG of axillary lymph node positive patients was higher than the negative ones both in young and postmenopausal women groups (P < 0.05 and P < 0.01). There was also a significant difference in VEGF, bFGF, FLK-1, FLG and MVC between the stage 0 - II and stage III - IV (P < 0.05 and P < 0.01) in both groups.

CONCLUSIONBreast cancer angiogenesis, characterized by the high expression of VEGF and bFGF, is directly correlated with the high tumor aggressiveness in the young women.

Adult ; Age Factors ; Aged ; Breast Neoplasms ; chemistry ; pathology ; Female ; Fibroblast Growth Factor 2 ; analysis ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Middle Aged ; Postmenopause ; Receptor, Fibroblast Growth Factor, Type 1 ; analysis ; Receptors, Estrogen ; analysis ; Vascular Endothelial Growth Factor A ; analysis ; Vascular Endothelial Growth Factor Receptor-2 ; analysis