Basic Fibroblast Growth Factor and Fibroblast Growth Factor Receptor-1 in Human Meningiomas

The expression of basic fibroblast growth factor (bFGF) and fibroblast growth factor receptor-1 (FGFR-1) in human meningiomas and the relationships between their expression and the tumors' histological features and angiogenesis were investigated by means of immunohistochemical technique. The expression of bFGF and FGFR-1 was detected by antibody of bFGF or FGFR-1. The tumors' angiogenesis was evaluated by microvascular density (MVD) and, which was observed by use of CD34-antibody immunohistochemically. The results showed that there were varied degrees of the expression of bFGF and FGFR-1 proteins in meningiomas. The expression was correlated with the tumors' histological characters and angiogenesis. It was concluded that bFGF and FGFR-1 might play important roles in meningiomas' angiogenesis and proliferation. The expression positive rate of bFGF and FGFR-1 may provide an indication of evaluating the histological and malignant degree of the tumor.

Role of fibroblast growth factor receptor 1 in the bone development and skeletal diseases

Accumulating data suggest that FGFs/FGFR1 plays essential roles in the bone development and human skeletal diseases. Conditional inactivation of fgfrl caused different phenotypes displaying in different cells or specific organs and revealed some novel functions of FGFR1 in bone development. Fgfrl mutation mainly induced 2 types of human skeletal diseases, craniosynostosis syndrome and dysplasias. Similar mutation of fgfrl in mouse model just mimicked the phenotype that happened in human. These fa- cilitate the investigation on the underlying mechanism of the diseases. Here we mainly focused on the ad- vance of FGFR1 function in the bone development and its mutation caused skeletal diseases.

Expression of fibroblast growth factor-2 and fibroblast growth factor receptor-1 protein in the hippocampus in rats exhibiting chronic stress-induced depression

There is evidence that the expression of members of the fibroblast growth factor （FGF） protein family is altered in post-mortem brains of humans suffering from major depressive disorder. The present study examined whether the expression of fibroblast growth factor-2 （FGF2） and fibroblast growth factor receptor-1 （FGFR1） protein is altered following chronic stress in an animal model. Rats were exposed to 35 days of chronic unpredictable mild stress, and then tested using open-field and sucrose consumption tests. Compared with the control group, rats in the chronic stress group exhibited obvious depressive-like behaviors, including anhedonia, anxiety and decreased mobility. The results of western blot analysis and immunohistochemical analysis revealed a downregulation of the expression of FGF2 and FGFR1 in the hippocampus of rats, particularly in the CA1, CA3 and dentate gyrus. This decreased expression is in accord with the results of post-mortem studies in humans with major depressive disorder. These findings suggest that FGF2 and FGFR1 proteins participate in the pathophysiology of depressive-like behavior, and may play an important role in the mechanism of chronic stress-induced depression.

Are there fibroblast growth factor receptor 1 mutations in a Chinese Kallmann syndrome family?

The present study examined 58 members of a Kallmann syndrome family and investigated whether there are fibroblast growth factor receptor 1 （FGFR1） gene mutations in this family. Genomic DNA from the proband and family members was subjected to PCR to amplify 18 exons of FGFR1, and the amplified products were sequenced to identify potential mutations. MRI of the olfactory bulb region was performed on suspected subjects. The patient and his father were diagnosed with Kallmann syndrome. A polymorphic site was found at 39542, with the proband and his parents being heterozygous （guanine ＋ cytosine）. However, healthy controls and the other members of this family were homozygous for guanine at this position.

Leukocyte cell-derived chemotaxin-2 and fibroblast growth factor 21 in alcohol-induced liver cirrhosis

BACKGROUND The importance of early diagnosis of alcoholic liver disease underscores the need to seek better and especially non-invasive diagnostic procedures.Leukocyte cellderived chemotaxin-2(LECT2)has been widely studied to determine its usefulness in monitoring the course of non-alcoholic fatty liver disease but not for alcoholic liver cirrhosis(ALC).AIM To determine the concentration of LECT2 in the blood serum of patients in relation to progressive stages of ALC,its relation to fibroblast growth factor 1(FGF-1)and FGF-21,and to examine the possible wider use of LECT2 in diagnosing ALC.METHODS A retrospective case-control study was conducted with 69 ALC cases and 17 controls with no ALC.Subjects were recruited from the region of Lublin(eastern Poland).Liver cirrhosis was diagnosed based on clinical features,history of heavy alcohol consumption,laboratory tests,and abdominal ultrasonography.The degree of ALC was evaluated according to Pugh-Child criteria(the Pugh-Child score).Blood was drawn and,after centrifugation,serum was collected for analysis.LECT2,FGF-1,and FGF-21 were determined using enzyme-linked immunosorbent assay kits.RESULTS The LECT2 Levels in the control group were 18.99±5.36 ng/mL.In the study groups,they declined with the progression of cirrhosis to 11.06±6.47 ng/mL in one group and to 8.06±5.74 ng/mL in the other(P<0.0001).Multiple comparison tests confirmed the statistically significant differences in LECT2 Levels between the control group and both test groups(P=0.006 and P<0.0001).FGF-21 Levels were 44.27±64.19 pg/mL in the first test group,45.4±51.69 pg/mL in the second(P=0.008),and 13.52±7.51 pg/mL in the control group.The difference between the control group and the second test group was statistically significant(P=0.007).CONCLUSION We suggest that LECT2 may be a non-invasive diagnostic factor for alcoholinduced liver cirrhosis.The usefulness of LECT2 for non-invasive monitoring of alcohol-induced liver cirrhosis was indirectly confirmed by the multiple regression model developed on the basis of our statistical analysis.

EXPRESSION AND SIGNIFICANCE OF BASIC FIBROBLAST GWOWTH FACTOR AND FIBROBLAST GROWTH FACTOR RECEPTOR-1 IN OVARIAN EPITHELIAL NEOPLASM

Objective To study the relevance of expression of basic fibroblast growth factor (bFGF), fibroblast growth factor receptor 1 (FGFR 1) and carcinogenesis and progression of ovarian epithelial neoplasm. Methods Ten cases of normal ovarian tissues and 75 cases of ovarian epithelial neoplasm tissues were detected by immunohistochemical methods: S P for bFGF, FGFR 1,double immunohistochemistry Lab SA for Ki 67 antigen and bFGF. Results The expression level of bFGF, FGFR 1in ovarian epithelium and ovarian epithelial neoplasm showed a step wise increase in the following order:normal <benign <borderline <malignant; The expression level and intensity of bFGF and FGFR 1 were increased with the decrease of differentiation degree and increase of clinical stage in ovarian carcinoma; There was no statistical difference between the expression of bFGF, FGFR 1 in serous cystadenocarcinoma and that of mucinous cystadenocarcinoma; The expression of bFGF was correlated with that of FGFR 1 in neoplastic tissues; There were positive expression rates of bFGF and Ki 67 antigen in ovarian epithelial neoplasm. Conclusion As an important proliferative factor, bFGF plays an important role in carcinogenisis and progression of ovarian epithelial neoplasm.

Overexpression of the receptor tyrosine kinase EphA4 in human gastric cancers

AIM: To clarify the expression and role of Ephrin receptor A4 (EphA4) in gastric cancer in relation to clinicopathological characteristics and the expression of fibroblast growth factor receptor 1 (FGFR1) and ephrin ligands. METHODS: Eleven gastric carcinoma cell lines, 24 paired surgical fresh specimens of gastric adenocarcinoma and adjacent nontumor tissue, 74 conventional formalin-fixed, paraffin-embedded tumor specimens, and 55 specimens spotted on tissue microarray (TMA) were analyzed. Reverse transcription-PCR (RT-PCR), real-time RT-PCR, immunohistochemistry, and cell growth assays were performed. RESULTS: Overexpression of EphA4 mRNA expres-sion was observed in 8 (73%) of 11 gastric cancer cell lines and 10 (42%) of 24 gastric cancer tissues. Over-expression of EphA4, analyzed by immunohistochemistry, was observed in 62 (48%) of 129 gastric cancer tissues. EphA4 overexpression, at the protein level, was significantly associated with depth of invasion and recurrence. EphA4 overexpression was also correlated with FGFR1 overexpression. Patients with EphA4-positive cancer had significantly shorter overall survival periods than did those with EphA4-negative cancer (P = 0.0008). The mRNAs for ephrin ligands were coexpressed in various combinations in gastric cancer cell lines and cancer tissues. Downregulation of EphA4 expression by siRNA in EphA4-overexpressing gastric cancer cell lines resulted in a significant decrease in cell growth. CONCLUSION: Our results suggest that overexpres-sion of EphA4 plays a role in gastric cancer.

Fibroblast Growth Factor Receptor 1 Gene Amplification in Nonsmall Cell Lung Cancer

Objective： To review the prevalence and prognostic significance of fibroblast growth factor receptor 1 （FGFRI） amplification and to establish an association between FGFRI amplification and the clinical characteristics of nonsmall cell lung cancer （NSCLC）. Data Sources： We searched PubMed for English-language studies published between January 2010 and May 2016. Study Selection： We included all relevant articles, with no limitation of study design. Results： FGFRI amplification was reported in 8.7-20.0% of NSCLC cases and was significantly more frequent in squamous cell carcinomas （SCCs） （9.7-28.3%） than in adenocarcinomas （ADCs） （0-15.0%）. The rates of FGFRI amplification were as follows： males, 13.9-22.1%; females, 0-20.1%; Stage 1 NSCLC, 9.3-24.1%; Stage II NSCLC, 12.9-25.0%; Stage 111 NSCLC, 8.2-19.5%： Stage IV NSCLC, 0-12.5%; current smokers, 13.3-29.0%; former smokers, 2.5-23.0%; and nonsmokers, 0-22.2%. Overall survival was 43.9-70.8 months in patients with FGFRI amplification and 42.4-115.0 months in patients with no FGFRI amplification; disease-free survival was 22.5-58.5 months and 52.4-94.6 months, respectively. Conclusions： FGFR1 amplification is more frequent in SCCs than in ADCs. The association between FGFRI amplification and clinical characteristics （gender, smoking status, and disease stage） and the prognostic significance of FGFRI amplification in NSCLC remain controversial.

Vaccination with a Recombinant Chicken FGFR-1 Bypasses Immunological Tolerance against Self-FGFR-1 in Mice

The possibility that a recombinant protein vaccine based on xenogeneic homologous FGFR-1 of chicken induces production of autoantibodies against self-FGFR-1 in BALB/c mice was examined by using ELISA, Western blot analysis and ELISPOT assay respectively. Autoantibodies against mouse FGFR-1 were identified by Western blot analysis and ELISA. Compared with the two control groups, the number of APBCs, which were detected by ELISPOT assay, was significantly in- creased in the spleens of mice immunized with cFR1 （P〈0.05）. IgG1 and IgG2b, which were detected by ELISA, were the major subclasses and were substantially increased in response to chicken FGFR-1 when compared with control group. The recombinant chicken FGFR-1 protein used as a vaccine can induce autoantibodies against self-FGFR-1 in mice and provide a basis for the active immunotherapy of tumor angiogenesis.

Comparison of FGFR1 expression on lens epithelial cells between adults and fetuses

AIM: To study the differences of fibroblast growth factor receptor 1 (FGFR1) gene on human lens epithelial cells (HLECs) of adults and fetuses. METHODS: Indirect in situ RT-PCR was adopted for detection of FGFR1 gene. The cDNA of the nnRNA in the paraffin sections of fetus and adult HLEC was synthesized by reverse transcription reaction. After PCR amplification, in situ hybridization test was performed with synthesized oligonucleotide probe and relative quantification was carried out using image analysis. RESULTS: HLECs of adults and fetuses expressed FGFR1 gene, the expression level was higher in fetuses than in adults. The difference between them had significance (P<0.05). CONCLUSION: FGFR1 Exist in HLEC and the expression is age-related, which could be one of causes of the high occurrence of post operational after-cataract in children.

Anti-tumor Angiogenesis with a Recombinant Ag43/FGFR1 Chimeric Protein As a Model Antigen

In order to investigate the anti-tumor angiogenesis activity with a recombinant Ag43/FGFR1 chimeric protein(AF)vaccine in a mouse H22 hepatoma model,tumor volume and survival rate of the mice were studied at a 3-day interval.Microvessel density(MVD)was detected by immunohistochemistry.The endothelial deposition of autoantibodies within tumor tissues was examined by immunofluorescent staining,and anti-FGFR1 antibody-producing B cells(APBCs)were tested by enzyme-linked immunospot(ELISPOT)assay.Compared with t...

Expressions of TGF-β2, bFGF and ICAM-1 in lens epithelial cells of complicated cataract with silicone oil tamponade

AIM： To investigate the expression differences of transforming growth factor-β2（TGF-β2）, basic fibroblast growth factor（b FGF） and intercellular cell-adhesion molecule-1（ICAM-1） in lens epithelial cells（LECs） of complicated cataract with silicone oil tamponade and agerelated cataract. METHODS： Totally 150 eyes of 150 patients（aged 35 to 77y） were investigated, including 75 patients with complicated cataract after silicone oil tamponade and 75 patients with age-related cataract. The central piece of anterior capsules was collected during cataract surgery. TGF-β2, b FGF and ICAM-1 were detected in the 60 specimens of the two groups by immunohistochemistry. The expression levels of the three kinds of messenger ribonucleic acid（m RNA） were determined by real-time quantitative reverse transcriptionpolymerase chain reaction in the 90 specimens of the two groups.RESULTS： TGF-β2 was detected in the cytomembrane and cytoplasm of the LECs and b FGF was detected in the nucleus. ICAM-1 was positive in the cytomembrane of the LECs and the distribution of positive cells was uneven. The m RNA genes expression of the TGF-β2, b FGF and ICAM-1 was significant differences between the two groups and markedly increased in complicated cataract group（P〈0.05）.CONCLUSION： The up-regulated TGF-β2, b FGF and ICAM-1 maybe associate with the occurrence and development of complicated cataract with silicone oil tamponade.

FGF1纳米脂质体结合超声靶向微泡爆破技术治疗糖尿病心肌病的实验研究

目的 研究酸性成纤维细胞生长因子1（FGF1）纳米脂质体结合超声靶向微泡爆破技术（UTMD）对于糖尿病心肌病（DCM）的治疗效果.方法 健康雄性Sprague Dawley大鼠75只,随机数字表法选择15只作为正常对照组（对照组）,其余大鼠腹腔注射链脲佐菌素（70 mg/kg）建立糖尿病模型,成模后继续饲养16周,通过超声心动图筛选出DCM大鼠模型.将DCM大鼠按随机数字表法分为4组,即DCM模型组（DCM组,给予生理盐水治疗）、FGF1溶液治疗组（FGF1溶液组）、FGF1纳米脂质体治疗组（FGF1纳米脂质体组）和FGF1纳米脂质体＋UTMD治疗组（FGF1纳米脂质体＋UTMD组）,每组15只.采用水包水型乳化法结合冷冻干燥技术制备FGF1载药纳米脂质体.药物干预2周再继续饲养2周后,采用心导管评价各组大鼠心功能.处死大鼠后取出心肌组织,分别通过Masson胶原染色、TUNEL凋亡染色及CD31免疫组织化学染色测定各组大鼠心肌胶原容积分数（CVF）、心肌凋亡指数及心肌微血管密度（MVD）.结果 （1）FGF1纳米脂质体质量评价结果：扫描电镜观察空白及载药纳米脂质体均呈标准的椭球形,分散均匀且包封率高稳定性好.（2）各组大鼠心功能的心导管检测结果：FGF1纳米脂质体＋UTMD组大鼠左心室收缩末期压力、左心室内压最大上升和下降速率均明显高于DCM组、FGF1溶液组和FGF1纳米脂质体组（P均＜0.05）,而左心室舒张末期压力则明显低于DCM组、FGF1溶液组和FGF1纳米脂质体组（P均＜0.05）.（3）各组大鼠心肌CVF的测定结果：DCM组大鼠心肌CVF明显大于对照组（P＜0.05）.FGF1溶液组、FGF1纳米脂质体组和FGF1纳米脂质体＋UTMD组大鼠心肌CVF均明显小于DCM组（P均＜0.05）.而FGF1纳米脂质体＋UTMD组大鼠心肌CVF则进一步小于FGF1溶液组和FGF1纳米脂质体组（P均＜0.05）.（4）各组大鼠心肌组织MVD的检测结果：DCM组大鼠心肌组织MVD明显低于对照组（P＜0.05）.FGF1溶液组、FGF1纳米脂质体组和FGF1纳米脂质体＋UTMD组大鼠心肌组织MVD均明显高于DCM组（P均＜0.05）.FGF1纳米脂质体＋UTMD组大鼠心肌组织MVD则明显高于FGF1溶液组和FGF1纳米脂质体组（P均＜0.05）.（5）各组大鼠心肌细胞凋亡情况的检测结果：DCM组大鼠心肌细胞凋亡指数明显高于对照组（P＜0.05）.FGF1溶液组、FGF1纳米脂质体组和FGF1纳米脂质体＋UTMD组大鼠心肌细胞凋亡指数均明显低于DCM组（P均＜0.05）.而FGF1纳米脂质体＋UTMD组大鼠心肌细胞凋亡指数则进一步低于FGF1溶液组和FGF1纳米脂质体组（P均＜0.05）.结论 FGF1纳米脂质体结合UTMD可有效改善DCM大鼠心功能和心肌结构,有望成为治疗DCM的一种新方法.