2.Research Progress of Fibroblast Growth Factor Receptor Signaling Pathway in Breast Cancer.
Qiu-Sheng GUO ; Wen-Ming CAO ; Xiao-Jia WANG
Acta Academiae Medicinae Sinicae 2022;44(1):136-141
Breast cancer,one of the common malignant tumors in women,has shown rising incidence in recent years,posing a serious threat to women's health.The advancement of molecular biology facilitates the revealing of the relationships between signaling pathways and breast cancer.Fibroblast growth factor receptor (FGFR) signaling pathway plays an important role in the proliferation,survival,differentiation,migration,and apoptosis of breast cancer cells.Strategies targeting the FGFR signaling pathway thus exhibit a promising prospect in breast cancer treatment.
Apoptosis
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Breast Neoplasms/metabolism*
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Female
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Humans
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Receptors, Fibroblast Growth Factor/metabolism*
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Signal Transduction
3.The effects of Ligustrazine on the expression of bFGF and bFGFR in bone marrow in radiation injured mice.
Ning, WU ; Hanying, SUN ; Wenli, LIU ; Huizhen, XU ; Wu, LU
Journal of Huazhong University of Science and Technology (Medical Sciences) 2003;23(4):348-51
To study the expression of the bFGF and its receptor in the mouse bone marrow by treatment with acute radioactive injury and Ligustrazine, 56 mice were divided into 3 groups: normal group, radiation-injured group and Ligustrazine group. After irradiation by 6.0 Gy 60Co gamma-ray, each mouse was orally given 0.1 ml Ligustrazine twice a day for 13 days in Ligustrazine group, and each mouse in radiation injured group was orally given equal amount of saline. On the 3rd, 7th, 14th day after irradiation, bone marrow mono-nuclear cells (BMMNC) were counted, and the expression levels of bPGF and bFGFR in bone marrow were evaluated by immunohistochemistry and flow cytometry analysis respectively. On the 3rd, 7th, 14th day after irradiation, expression of bFGF in bone marrow were significantly lower than in normal group (P<0.05 or P<0.01). Expressions of bFGF and bFGFR were much higher in Ligustrazine treated group than that in the control group (P<0.05 or P<0.01). Ligustrazine potentiate the expression of bFGF and bFGFR in bone marrow MNC to recover the bone marrow hematopoiesis inductive microenvironment, which is one of the mechanisms by which Ligustrazine rebuild the bone marrow hematopoiesis after acute radioactive injury.
Bone Marrow Cells/metabolism
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Fibroblast Growth Factor 2/*biosynthesis
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Hematopoiesis/drug effects
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Pyrazines/*pharmacology
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Radiation Injuries, Experimental/*metabolism
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Radiation-Protective Agents/pharmacology
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Receptors, Fibroblast Growth Factor/*biosynthesis
4.Expression of aFGF, bFGF, and FGFR1 in ovarian epithelial neoplasm.
Yi ZHANG ; Ke-Jun GUO ; Hai SHANG ; Ya-Jun WANG ; Li-Guang SUN
Chinese Medical Journal 2004;117(4):601-603
Adult
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Aged
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Female
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Fibroblast Growth Factor 1
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genetics
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Fibroblast Growth Factor 2
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genetics
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Humans
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Middle Aged
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Neoplasm Staging
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Neoplasms, Glandular and Epithelial
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metabolism
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pathology
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Ovarian Neoplasms
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metabolism
;
pathology
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RNA, Messenger
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analysis
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Receptor Protein-Tyrosine Kinases
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genetics
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Receptor, Fibroblast Growth Factor, Type 1
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Receptors, Fibroblast Growth Factor
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genetics
5.The effects of Ligustrazine on the expression of bFGF and bFGFR in bone marrow in radiation injured mice.
Ning WU ; Hanying SUN ; Wenli LIU ; Huizhen XU ; Wu LU
Journal of Huazhong University of Science and Technology (Medical Sciences) 2003;23(4):348-351
To study the expression of the bFGF and its receptor in the mouse bone marrow by treatment with acute radioactive injury and Ligustrazine, 56 mice were divided into 3 groups: normal group, radiation-injured group and Ligustrazine group. After irradiation by 6.0 Gy 60Co gamma-ray, each mouse was orally given 0.1 ml Ligustrazine twice a day for 13 days in Ligustrazine group, and each mouse in radiation injured group was orally given equal amount of saline. On the 3rd, 7th, 14th day after irradiation, bone marrow mono-nuclear cells (BMMNC) were counted, and the expression levels of bPGF and bFGFR in bone marrow were evaluated by immunohistochemistry and flow cytometry analysis respectively. On the 3rd, 7th, 14th day after irradiation, expression of bFGF in bone marrow were significantly lower than in normal group (P<0.05 or P<0.01). Expressions of bFGF and bFGFR were much higher in Ligustrazine treated group than that in the control group (P<0.05 or P<0.01). Ligustrazine potentiate the expression of bFGF and bFGFR in bone marrow MNC to recover the bone marrow hematopoiesis inductive microenvironment, which is one of the mechanisms by which Ligustrazine rebuild the bone marrow hematopoiesis after acute radioactive injury.
Animals
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Bone Marrow Cells
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metabolism
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Female
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Fibroblast Growth Factor 2
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biosynthesis
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Hematopoiesis
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drug effects
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Male
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Mice
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Pyrazines
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pharmacology
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Radiation Injuries, Experimental
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metabolism
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Radiation-Protective Agents
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pharmacology
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Receptors, Fibroblast Growth Factor
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biosynthesis
6.Effect of ligustrazine on expressions of basic fibroblast growth factor and its receptor in bone marrow of mice with acute radiation injury.
Ning WU ; Han-ying SUN ; Wen-li LIU
Chinese Journal of Integrated Traditional and Western Medicine 2004;24(5):439-441
OBJECTIVETo study the expressions of basic fibroblast growth factor (bFGF) and its receptor (bFGFR) in bone marrow of mice with acute radiation injury, and to evaluate the effect of Ligustrazine (Lt) on them.
METHODSFifty-six Kunming mice of clean grade were randomly divided into 3 groups, the normal group, the control group and the Lt group. Mice in the latter two groups were once homogeneously systemic irradiated with 6.0 Gy of 60Co, with the absorption dose rate of 0.56 Gy/min, then treated with saline (0.2 ml/mice) or Lt (2 mg/mice) respectively, twice a day through gastrogavage for successive 13 days. Mice were sacrificed in batch on the 3rd, 7th and 14th day by cervical dislocation to collect the bilateral femoral bone marrow for preparing bone marrow mono-nuclear cell (BMMNC) suspension. The bFGFR expression on surface of BMMNC was determined by flow cytometry; and the bFGF expression level in one side of femoral bone marrow tissue was detected by immunohistochemistry with SABC-AP assay.
RESULTSThe bFGF expression in bone marrow of mice on the 3rd, 7th and 14th day after acute radiation injury all were significantly lower than that of the normal mice (P < 0.05 or P < 0.01). The expressions of bFGF and bFGFR in the Lt group detected were significantly higher than that in the control group detected at the corresponding time points (P < 0.05 or P < 0.01).
CONCLUSIONBy way of enhancing bFGF expression in bone marrow and bFGFR expression on surface of BMMNC to accelerate the repairing of homopoietic micro-environment in bone marrow might be one of the mechanisms of Lt in promoting hemopoietic function reconstitution after acute radiation injury.
Animals ; Bone Marrow Cells ; metabolism ; Female ; Fibroblast Growth Factor 2 ; biosynthesis ; genetics ; Hematopoiesis ; drug effects ; Male ; Mice ; Pyrazines ; pharmacology ; Radiation Injuries, Experimental ; metabolism ; Random Allocation ; Receptors, Fibroblast Growth Factor ; biosynthesis ; genetics
7.Relationship of overexpression of angiogenesis factors and their receptors with invasive growth of keloid.
Du-yin JIANG ; Xiao-bing FU ; Wei CHEN ; Tong-zhu SUN
Chinese Journal of Plastic Surgery 2004;20(2):128-131
OBJECTIVETo study the relationship between invasive growth and the angiogenesis factors and their receptors in keloid.
METHODSBiopsies from 17 keloid (Ke) were divided into atrophy group (Ke-A, n = 9), proliferating group (Ke-P, n = 13), infiltrating group (Ke-I, n = 9), normal skin around Ke (Ke-N, n = 10) and normal skin (NS, n = 10). The histology, immunohistochemistry and computerized imaging analysis were used for the study. The levels of basic fibroblast growth factor (bFGF) and its receptor-Flg, vascular endothelial growth factor (VEGF) and VEGF/KDR complex (11B5), and platelet derived growth factor (PDGF-A) and its receptor-PDGFR-alpha, and alpha-smooth muscle actin (alpha-SMA) were determined in specimens with immuneohistochemical staining.
RESULTSIn all 5 groups, bFGF, Flg, VEGF, 11B5, PDGF-A, and PDGFR-alpha were all expressed in fibroblasts (Fb), monocyte-phagocytes, vascular endothelial cells, adventitial cells, epidermal (cells and epithelial cells in appendage. The intensities of staining ranked as follows: Ke-I > Ke-N approximately equal to Ke-P > Ke-A approximately equal to NS, Flg > hFGF approximately equal to PDGFR-alpha > PDGF-A approximately equal to 11B5 > VEGF (P < 0.05 to approximately 0.01). 11B5 and VEGF were expressed (intensively in alpha-SMA positive myofibroblasts only in Ke-I group. The histological observation showed hyperplasia of endothelial cells and obliteration of microvessels.
CONCLUSIONThe invasive growth of keloid may be related to the overexpression of angiogenesis factors and their receptors. The abnormal expression of 11B5 in myofibroblasts may be one of the important factors associated with tumor-like growth feature in the invasive parts sites of keloid. The results suggest that inhibition of these biological activities would be of significance in clinical therapy.
Adolescent ; Adult ; Aged ; Angiogenesis Inducing Agents ; analysis ; Child ; Child, Preschool ; Female ; Fibroblast Growth Factors ; analysis ; Fibroblasts ; chemistry ; pathology ; Humans ; Immunohistochemistry ; Infant ; Keloid ; metabolism ; pathology ; Male ; Middle Aged ; Platelet-Derived Growth Factor ; analysis ; Receptor Protein-Tyrosine Kinases ; analysis ; Receptor, Fibroblast Growth Factor, Type 1 ; Receptor, Platelet-Derived Growth Factor alpha ; analysis ; Receptors, Fibroblast Growth Factor ; analysis ; Receptors, Growth Factor ; analysis ; Skin ; chemistry ; pathology ; Vascular Endothelial Growth Factor A ; analysis
8.Pulmonary expression levels of fibroblast growth factor receptors and lung fibrosis in mice at different ages.
Xiaoxi LI ; Hongen CHANG ; Wenqing NAI ; Xiaoyan BAI ; Ying SUN ; Yanlin YU ; Meng DAI
Journal of Southern Medical University 2013;33(4):607-610
OBJECTIVETo explore the correlation of pulmonary expressions of fibroblast growth factor receptors (FGFR1-4) with lung fibrosis and aging.
METHODSReal-time fluorescence quantitative PCR was used to detect the expression levels of FGFR1-4 in the lung tissues, and lung fibrosis was observed by HE and Masson staining in mice at different ages.
RESULTSThe 4 subtypes of FGFR showed different expression levels in the lung tissues of mice, and FGFR2 had the highest expressions. The expression levels of all the 4 FGFR subtypes in 8-month-old mice were significantly lower than those in 5-week-old mice. The 8-month-old mice tended to present with histological changes of lung fibrosis.
CONCLUSIONFGFR expressions is down-regulated with aging in mice. Among the FGFR subtypes, FGFR2 is expressed at the highest level. The occurrence of lung fibrosis with aging is probably associated with down-regulated FGFR expression. FGF/FGFR signaling may participate in the aging process and regulation of lung fibrosis.
Aging ; physiology ; Animals ; Lung ; metabolism ; pathology ; Male ; Mice ; Mice, Inbred C57BL ; Pulmonary Fibrosis ; metabolism ; pathology ; physiopathology ; Receptors, Fibroblast Growth Factor ; classification ; metabolism ; Signal Transduction
9.Insulin-like growth factor-II and basic fibroblast growth factor affect periodontal ligament cells expressing osteoprotegerin in vitro.
West China Journal of Stomatology 2004;22(5):366-369
OBJECTIVEThis study was carried out to investigate the effects of insulin-like growth factor-II (IGF-II) and basic fibroblast growth factor (bFGF) on osteoprotegerin (OPG) secretion of periodontal ligament cells (PDLCs).
METHODSHealthy human premolars extracted for orthodontic reasons from 12-14 years old donators were obtained, and periodontal tissues were collected and cultured to obtain PDL cells. Primary or first passage PDLCs were cloned by means of limited dilutions. PDLCs with osteoblastic phenotypes were characterized as follows: Alkaline phosphatase activity, collagen III production and bone-like nodules formation. IGF-II and bFGF were added into culture media and their effects on PDLCs proliferation and OPG secretion were observed. The OPG concentrations in cell culture supernatants were detected by sandwich ELISA. Living cell numbers were demonstrated by MTT test. The average levels of OPG secretion by a single cell were calculated by dividing OPG concentration with MTT-test result.
RESULTSBoth IGF-II and bFGF upregulated the mtt values (P < 0.05), but ICF-II downregulated the opg/mtt values (P < 0.05), whereas bFGF had no significant effect on opg/mtt values (P > 0.05).
CONCLUSIONIGF-II enhances the proliferation of PDL cells but prohibits OPG secretion. Although bFGF has the same effect on the proliferation of PDL cells, it has no effect on OPG secretion. Before cytokines were used to enhance periodontal regeneration, their effects on local bone balance should also be studied.
Adolescent ; Cells, Cultured ; Child ; Fibroblast Growth Factor 2 ; pharmacology ; Glycoproteins ; biosynthesis ; Humans ; Insulin-Like Growth Factor II ; pharmacology ; Osteoprotegerin ; Periodontal Ligament ; cytology ; drug effects ; metabolism ; Receptors, Cytoplasmic and Nuclear ; biosynthesis ; Receptors, Tumor Necrosis Factor ; biosynthesis
10.Functional defect of partial homing receptor on human cord blood hematopoietic stem/progenitor cells.
Xu-Han ZHANG ; Zi-Min SUN ; Hui-Lan LIU ; Xing-Bing WANG ; Liang-Quan GENG
Journal of Experimental Hematology 2010;18(2):445-449
This study was aimed to investigate the function defect of partial homing receptor on cord blood hematopoietic stem cells (CBHSC) and explore efficacy and feasibility of intervention in vitro. The expression and activity of active groups in P, E-selectin ligands on CD34+ cells from cord blood, bone marrow and peripheral blood were detected by flow cytometry; meanwhile the expression of active groups in selectin ligands on CD34+ cells treated by fucosyl transferase in vitro was determined by flow cytometry. The results indicated that the expression levels of CD26 on the surface of stem/progenitor cells (CD34+) from cord blood, bone marrow and peripheral blood were (7.62+/-0.63)%, (6.35+/-0.89)% and (6.18+/-0.91)% (p>0.05) respectively. And the activities of CD26 of the three sources of stem cells were 67.15 U/1000 cells (1 U=1 pmol/min), 26.85 U/1000 cells and 20.95 U/1000 cells respectively, in which the activity of CD26 on surface of CD34+ from cord blood was significantly higher than that from other both sources (p<0.01). The expression levels of P-selectin ligand on the stem/progenitor cells three kinds were (83.46+/-6.33)%, (15.65+/-0.89)% and (80.17+/-6.85)%, and the expression levels of E-selectin ligand on stem/progenitor cells of three kinds were (25.31+/-1.03)%, (26.34+/-0.89)% and (29.79+/-1.78)% respectively. The expression of E-selectin ligand on the surface of cord blood stem/progenitor cell CD34+ increased from (25.31+/-1.03)% to (63.23+/-1.08)% after glycosylation engineering. It is concluded that there is no significant difference of the expression of CD26 between the three sources of stem/progenitor cells, but the activity of CD26 in cord blood was obviously higher than that in bone marrow and peripheral blood. The expression of P-selectin ligand on bone marrow stem/progenitor cell was lower than that on stem cells of cord blood and peripheral blood. Glycosylation engineering can promote and elevate the expression of E-selectin ligand on the surface of CD34+ cells from cord blood.
Antigens, CD34
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metabolism
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Bone Marrow Cells
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cytology
;
metabolism
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Cells, Cultured
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Dipeptidyl Peptidase 4
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metabolism
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Fetal Blood
;
cytology
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Hematopoietic Stem Cells
;
cytology
;
metabolism
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Humans
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Receptors, Fibroblast Growth Factor
;
metabolism
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Sialoglycoproteins
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metabolism
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Stem Cells
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cytology
;
metabolism