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

Adipose tissue-derived stem cell (ASCs) are an attractive source of stem cells with therapeutic applicability in various fields for regenerating damaged tissues because of their stemness characteristics. However, little has reported on evaluating adverse responses caused by human ASC therapy. Therefore, in the present study, a clinical assessment after human ASC transplantation into dogs was undertaken. A total of 12 healthy male dogs were selected and divided into four groups: saline infusion, saline bolus, ASC infusion, and ASC bolus groups. Physical assessment and blood analysis were performed following ASC transplantation, and the concentrations of angiogenic factors, and pro- and anti-inflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA). There were no adverse vital sign responses among the dogs. Blood analyses revealed no remarkable complete blood count or serum chemistry results. ELISA results for angiogenic and anti-inflammatory factors including matrix metalloproteinase 9 (MMP9), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), and interleukin-10 (IL-10) were significantly higher in the two ASCs groups than in the controls. In conclusion, this study demonstrated that transplantation of human ASCs produced no adverse effects and could be used safely in dogs. In addition, human ASCs could be involved in modulating secretions of angiogenic factors including MMP9, VEGF, bFGF, and HGF and anti-inflammatory factor IL-10.
Angiogenesis Inducing Agents ; Animals ; Blood Cell Count ; Chemistry ; Cytokines ; Dogs ; Enzyme-Linked Immunosorbent Assay ; Fibroblast Growth Factor 2 ; Hepatocyte Growth Factor ; Humans ; Interleukin-10 ; Male ; Matrix Metalloproteinase 9 ; Stem Cell Transplantation ; Stem Cells ; Transplantation ; Vascular Endothelial Growth Factor A ; Vital Signs

BACKGROUNDThe aim of this study was to prospectively study the changes in neutrophil elastase (NE), fibroblast growth factor 9 (Fgf9), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase 1 (TIMP-1) in sputum induced during the early period after lung volume reduction surgery (LVRS).

METHODSFrom April to October 2005, ten consecutive patients with chronic obstructive pulmonary disease (COPD) underwent LVRS. Ten non-small cell lung cancer patients (stage II - IIIa) received lobectomy as a control group. The induced sputum was collected from both groups at six different times (two weeks before operation and postoperatively at 1, 2, 4, 6 and 10 days). The level of NE, Fgf9, MMP-9 and TIMP-1 were measured using enzyme-linked immunosorbent assay.

RESULTSThe pulmonary function (FEV(1)%) and arterial blood gases (PaO(2) and PaCO(2)) were significantly different between the groups. There were no significant differences in age, ejection fraction (EF), and operation duration, but hemoglobin in the LVRS group was statistically higher than in the controls. At certain times, there were significant differences in NE, MMP-9, TIMP-1 and MMP-9/TIMP-1 (P < 0.05) but not in Fgf9 between the two groups. The levels of NE and TIMP-1 were maximal at 2 days postoperatively and that of MMP-9 and MMP-9/TIMP-1 at 4 days postoperatively in the LVRS group. In the control group, maximal levels of NE and TIMP-1 occurred at 2 days postoperatively and that of MMP-9 and MMP-9/TIMP-1 at 1 day postoperatively. Ten days after surgery, all values of the control group were not significantly different from the baseline. In the LVRS group, the levels were significantly different from the pre-operative values (P < 0.05) apart from TIMP-1.

CONCLUSIONThe levels of NE, MMP-9, TIMP-1 and MMP-9/TIMP-1 of the LVRS group were different from those of the control group. The time course of these changes may be related to LVRS and the underlying process of COPD.

Female ; Fibroblast Growth Factor 9 ; analysis ; Humans ; Leukocyte Elastase ; analysis ; Lung Neoplasms ; surgery ; Male ; Matrix Metalloproteinase 9 ; analysis ; Middle Aged ; Pneumonectomy ; Prospective Studies ; Pulmonary Disease, Chronic Obstructive ; surgery ; Sputum ; chemistry ; Tissue Inhibitor of Metalloproteinase-1 ; analysis

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: In order to investigate the interaction between the cytokines and keratinocyte and determine the role of cytokines in hyperproliferative of chronic otitis media with cholesteatoma, we observe the expression of matrix metalloproteinase 9 (MMP9), vascular endothelial growth factor (VEGF), keratinocyte growth factor (KGF) and its receptor (KGFR) in middle ear cholesteatoma. METHOD: We examined the expression of MMP9, VEGF, KGF, KGFR and Ki-67 by immunohistochemistry in 50 specimens from chronic otitis media with cholesteatoma and 15 specimens from the normal skin of external auditory meatus. Ki-67 as an evaluation of cholesteatoma proliferation markers were used to detect the keratinocyte proliferative activity. RESULT: (1) The expression of VEGF and MMP9 in cholesteatoma specimens was higher than normal skin, and the difference was statistically significant (t = 4.914, P < 0.01; t = 3.284, P < 0.01). (2) The expression of KGF and KGFR in middle ear tissues was higher than normal skin, and the difference was statistically significant (t = 4.814, P < 0.01; t = 3.104, P < 0.01); The expression of KGF and KGFR increased, and the expression of Ki-67 also correspondly increased in the cholesteatoma. (3) In the tissue MMP9 and VEGF were positive. Mean optical density increased as well. KGF expression also increased accordingly. CONCLUSION MMP9, VEGF, KGF and KGFR proteins played an important role in hyperproliferation of cholesteatoma tissues. VEGF, MMP9 and KGF had a synergistic effect in hyperproliferation of cholesteatoma tissues.
Cholesteatoma, Middle Ear ; pathology ; Cytokines ; metabolism ; Ear Canal ; metabolism ; Ear, Middle ; metabolism ; Fibroblast Growth Factor 7 ; metabolism ; Humans ; Immunohistochemistry ; Keratinocytes ; cytology ; Ki-67 Antigen ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Otitis Media ; pathology ; Receptor, Fibroblast Growth Factor, Type 2 ; metabolism ; Vascular Endothelial Growth Factor A ; metabolism

BACKGROUNDFibroblast growth factor 9 (FGF9), expressed in brain, kidney and developing skeletal tissues, can physiologically inhibit endochondral ossification; but little is known about how FGF9 affects osteoblasts and its detailed regulatory mechanism. Here we examined the effect of FGF9 on the activity of the murine Runt-related transcription factor 2 (Runx2) gene promoter in preosteoblast MC3T3-E1 and premyoblast C2C12 cells.

METHODSPlasmids containing the Runx2 promoter region were transfected into MC3T3-E1 and C2C12 cells and stably transfected cell lines were established. The method of luciferase reporter gene activation was used to examine the effects of FGF9 on the promoter activity.

RESULTSFGF9 (10 ng/ml) increased Runx2 promoter activity in MC3T3-E1 cells. When MC3T3-E1 cells were treated with FGF9 plus the various inhibitors or activator of the intracellular signaling transducation pathways, including 10 micromol/L U0126 (the inhibitor of mitogen-activated protein kinase kinase), 10 micromol/L SB203580 (the inhibitor of p38/mitogen activated protein kinase), or 1 micromol/L C6 ceramide (an activator of mitogen activated protein kinase), the luciferase expression did not change significantly compared with that of the cells treated with FGF9 only. However, when C2C12 cells were treated with 10 ng/ml FGF9, Runx2 gene promoter activity first decreased and then increased over a period of 1 to 5 days. Among the above inhibitors, only U0126 (10 micromol/L) completely blocked the effects of FGF9 on Runx2 gene promoter activity.

CONCLUSIONSOur data showed that FGF9 can affect Runx2 gene promoter activity in MC3T3-E1 and C2C12 cells. The action of FGF9 appears to depend partly on the mitogen-activated protein kinase kinase/mitogen-activated protein kinase pathways in C2C12 cells.

Animals ; Cells, Cultured ; Core Binding Factor Alpha 1 Subunit ; genetics ; Fibroblast Growth Factor 9 ; pharmacology ; MAP Kinase Signaling System ; Mice ; Myoblasts ; drug effects ; metabolism ; Osteoblasts ; drug effects ; metabolism ; Promoter Regions, Genetic

OBJECTIVETo measure plasma levels of VEGF, bFGF and MMP-9 in advanced non-small-cell lung cancer (NSCLC) patients and evaluate their prognostic value.

METHODSThe plasma levels of VEGF, bFGF and MMP-9 in 46 cases with advanced NSCLC were measured by ELISA before chemotherapy and in 30 cases after chemotherapy.

RESULTSThe plasma levels of VEGF, bFGF and MMP-9 in patients before chemotherapy were significantly higher than those in healthy control persons (P < 0.05). The correlation between plasma levels of VEGF and bFGF was significant, Spearman's r = 0.329 (P = 0.027). No correlation was found among the levels of angiogenic factors studied above and the following clinical parameters such as age, sex, histological subtype, differentiation of tumor cells, TNM-stage and also blood leukocyte, hemoglobin and platelet counts. The plasma level of MMP-9 in patients with extensive metastasis (including bone metastasis) was significantly higher than that in patients with bone metastasis only (P = 0.013). Reduction of plasma bFGF level after chemotherapy was a unique independent good prognostic factor (RR = 11.737, P = 0.02).

CONCLUSIONThe measurement of plasma levels of such angiogenic factors as VEGF, bFGF and MMP-9 in advanced NSCLC is helpful for prediction of metastasis tendency and evaluation of prognosis.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Non-Small-Cell Lung ; blood ; secondary ; Enzyme-Linked Immunosorbent Assay ; Female ; Fibroblast Growth Factor 2 ; blood ; Humans ; Lung Neoplasms ; blood ; pathology ; Male ; Matrix Metalloproteinase 9 ; blood ; Middle Aged ; Neoplasm Metastasis ; Prognosis ; Vascular Endothelial Growth Factor A ; blood

BACKGROUNDIn multiple myeloma (MM), bone marrow angiogenesis parallels tumour progression and correlates with disease activity. Recent studies have proved resveratrol possesses antiangiogenic activity in vitro and in vivo. In this study, we examined the effects of resveratrol on myeloma cell dependent angiogenesis and the effects of resveratrol on some important angiogenic factors of RPMI 8226 cells.

METHODSRPMI 8226 cells were cocultured with human umbilical vein endothelial cells (HUVECs) to evaluate the effects of myeloma cells on angiogenesis. The RPMI 8226 cells were treated with various concentrations of resveratrol (6.25 - 50.00 micromol/L) for different times (12 - 72 hours). Reverse transcriptase polymerase chain reaction (RT-PCR) was used to assay vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), metalloproteinases (MMP)-2 and MMP-9 mRNA. Gelatin zymography was used to analyze MMP-2 and MMP-9 activity. VEGF and bFGF proteins secreted by the cells in the medium were quantified by enzyme linked immunosorbent assay (ELISA).

RESULTSCell proliferation, migration and differentiation of HUVECs markedly increased by coculture with RPMI 8226 cells. Resveratrol inhibited proliferation, migration and tube formation of HUVECs cocultured with myeloma cells in a dose dependent manner. Treatment of RPMI 8226 cells with resveratrol caused a decrease in MMP-2 and MMP-9 activity. Resveratrol inhibited VEGF and bFGF protein expression in a dose and time dependent manner. Furthermore, decreased levels of VEGF, bFGF, MMP-2 and MMP-9 mRNA from cells treated with various concentrations of resveratrol confirmed its antiangiogenic action at the level of gene expression.

CONCLUSIONSResveratrol inhibits multiple myeloma angiogenesis by regulating expression and secretion of VEGF, bFGF, MMP-2 and MMP-9. Resveratrol may be a potential candidate for the treatment of multiple myeloma.

Angiogenesis Inhibitors ; pharmacology ; Antineoplastic Agents, Phytogenic ; pharmacology ; Cell Line, Tumor ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Fibroblast Growth Factor 2 ; analysis ; genetics ; Humans ; Matrix Metalloproteinase 2 ; analysis ; Matrix Metalloproteinase 9 ; analysis ; Multiple Myeloma ; blood supply ; drug therapy ; pathology ; RNA, Messenger ; analysis ; Stilbenes ; pharmacology ; Vascular Endothelial Growth Factor A ; analysis ; genetics

OBJECTIVETo investigate the mRNA expression of bFGF and MMP-9 in gastric carcinomas and to find their correlation with tumor microvascular density (MVD), invasion, metastasis and patients survival.

METHODSIn situ hybridization and immunohistochemistry technique were used to test the expression of bFGF mRNA and MMP-9 mRNA and protein of CD34 in 105 specimens of gastric carcinoma.

RESULTSIn situ hybridization revealed that the positive rates of bFGF mRNA and MMP-9 mRNA were 60.95 and 58.1%, respectively; The mean MVD (46.09 +/- 11.52, 43.75 +/- 13.41 piece/0.72 mm(2)) in tumors with bFGF mRNA and MMP-9 mRNA positive expression was significantly higher than that (29.41 +/- 12.47; 33.45 +/- 13.92 piece/0.72 mm(2)) in tumors with their negative expression, respectively; The positive expression rates of bFGF and MMP-9 mRNA were correlated to invasion depth (r(s) = 0.211, P = 0.031; r(s) = 0.335, P = 0.001, respectively), growing pattern (r(s) = 0.324, P = 0.001; r(s) = 0.267, P = 0.006, respectively), vessel invasion (r(s) = 0.579, P = 0.001; r(s) = 0.209, P = 0.032, respectively), lymph node metastasis (r(s) = 0.405, P = 0.001; r(s) = 0.343, P = 0.001, respectively) and distant metastasis (r(s) = 0.474, P = 0.001; r(s) = 0.468, P = 0.001, respectively), but not correlated to tumor type (r(s) = 0.134, P = 0.173; r(s) = 0.103, P = 0.145, respectively) and differentiation (r(s) = 0.096, P = 0.332; r(s) = 0.102, P = 0.298, respectively); And then, the mean MVD in tumors with infiltrating type, stage T(3)-T(4), vessel invasion, lymph node metastasis and distant metastasis was significantly higher than that in tumors with expanding type (t = 10.105, P = 0.001), stage T(1)-T(2) (t = 5.961, P = 0.001), non-vessel invasion (t = 7.394, P = 0.001), non-lymph node metastasis (t = 3.819, P = 0.01) and non-distant metastasis (r = 10.578, P = 0.001); There was a positive relationship between MVD and bFGF mRNA and MMP-9 mRNA (t = 3.207, P = 0.002; t = 7.035, P = 0.001), respectively; the mean survival time in cases with positive bFGF mRNA and MMP-9 mRNA and MVD value >/= 39.5 was significantly shorter than that in cases with their negative expression and MVD value < 39.5.

CONCLUSIONSbFGF and MMP-9 promote angiogenesis in gastric cancer. Test of the expression of bFGF and MMP-9 may act as an useful index to determine angiogenesis, invasion, metastasis and patients survival.

Adult ; Aged ; Biomarkers, Tumor ; biosynthesis ; genetics ; Female ; Fibroblast Growth Factor 2 ; biosynthesis ; genetics ; Humans ; In Situ Hybridization ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; Male ; Matrix Metalloproteinase 9 ; biosynthesis ; genetics ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; RNA, Messenger ; biosynthesis ; Stomach Neoplasms ; metabolism ; mortality ; pathology ; Survival Rate

OBJECTIVETo investigate the effects of hydroxy safflor yellow A (HSYA) on the expression of bFGF protein and MMP-9 mRNA or protein of transplantation tumor of gastric adenocarcinoma cell line BGC-823 in nude mice.

METHODThe BGC-823 cells were subcutaneously injected into the right anterior armpit of BALB/C nu/nu nude mice, and the animal model of transplantation tumor was established. The experimental groups were treated with HSYA at concentration of 0.056 and 0.028 g x L(-1) and cyclophosphamide at 2 g x L(-1), or with physiologic saline. The tumor inhibitory effect was observed, and the mRNA expression of MMP-9 of transplantation tumor was detected by real time-fluorescent quantitation PCR and the protein expression of MMP-9 and bFGF were detected by enzyme linked immunosorbent assay.

RESULTThe IR in the group with HSYA at the concentration of 0.028 g x L(-1) is higher than in the group with normal sodium. After treatment with HSYA, the mRNA expression of MMP-9 has significant difference at the concentration of 0.028 g x L(-1) as compared with physiologic saline-treated group (P < 0.05), but the protein expression of MMP-9 and bFGF is obviously less than that in the physiologic saline-treated group (P < 0.05).

CONCLUSIONThe possible mechanism of HSYA in given concentration to antagonize tumor angiogenesis may be related with inhibiting the protein expression of MMP-9 and bFGF or the mRNA expression of MMP-9 in tumor tissue to reduce the degradation of blood vessel basilar membrane, and to restrain the migration of blood vessel and decrease the tumor vascularization.

Animals ; Cell Line, Tumor ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Fibroblast Growth Factor 2 ; genetics ; metabolism ; Gene Expression Regulation, Neoplastic ; drug effects ; Humans ; Matrix Metalloproteinase 9 ; genetics ; metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Neovascularization, Pathologic ; Stomach Neoplasms ; drug therapy ; genetics ; metabolism ; pathology