Fibroblast growth factors, their receptors and signaling.
TL;DR: FGF signaling also appears to play a role in tumor growth and angiogenesis, and autocrine FGF signaling may be particularly important in the progression of steroid hormone-dependent cancers to a hormone-independent state.
Abstract: Fibroblast growth factors (FGFs) are small polypeptide growth factors, all of whom share in common certain structural characteristics, and most of whom bind heparin avidly. Many FGFs contain signal peptides for secretion and are secreted into the extracellular environment, where theycan bind to the heparan-like glycosaminoglycans (HLGAGs) of the extracellular matrix (ECM). From this reservoir, FGFs mayact directlyon target cells, or theycan be released through digestion of the ECM or the activityof a carrier protein, a secreted FGF binding protein. FGFs bind specific receptor tyrosine kinases in the context of HLGAGs and this binding induces receptor dimerization and activation, ultimatelyresulting in the activation of various signal transduction cascades. Some FGFs are potent angiogenic factors and most playimportant roles in embry onic development and wound healing. FGF signaling also appears to playa role in tumor growth and angiogenesis, and autocrine FGF signaling maybe particularlyimportant in the progression of steroid hormone-dependent cancers to a hormone-independent state.
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TL;DR: In this article, the FGFR4 Gly388Arg polymorphism in the transmembrane domain of the fibroblast growth factor-4 receptor (FGFR4) has been shown to increase genetic susceptibility to cancers.
Abstract: The fibroblast growth factor-4 receptor (FGFR4) is a member of receptor tyrosine kinase. The FGFR4 Gly388Arg polymorphism in the transmembrane domain of the receptor has been shown to increase genetic susceptibility to cancers. However, its prognostic impact in cancer patients still remains controversial. Herein, we performed this meta-analysis to evaluate the clinicopathological and prognostic impacts of the FGFR4 Gly388Arg polymorphism in patients with cancer. We carried out a computerized extensive search using PubMed, Medline, and Ovid Medline databases up to July 2021. From 44 studies, 11,574 patients were included in the current meta-analysis. Regardless of the genetic models, there was no significant correlation of the FGFR4 Gly388Arg polymorphism with disease stage 3/4. In the homozygous model (Arg/Arg vs. Gly/Gly), the Arg/Arg genotype tended to show higher rate of lymph node metastasis compared with the Gly/Gly genotype (odds ratio = 1.21, 95% confidence interval (CI): 0.99-1.49, p = 0.06). Compared to patients with the Arg/Gly or Arg/Arg genotype, those with the Gly/Gly genotype had significantly better overall survival (hazard ratios (HR) = 1.19, 95% CI: 1.05-1.35, p = 0.006) and disease-free survival (HR = 1.25, 95% CI: 1.03-1.53, p = 0.02). In conclusion, this meta-analysis showed that the FGFR4 Gly388Arg polymorphism was significantly associated with worse prognosis in cancer patients. Our results suggest that this polymorphism may be a valuable genetic marker to identify patients at higher risk of recurrence or mortality.
2 citations
01 Jan 2008
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TL;DR: In this article , the authors used a combination of cultures, keratinocyte sheets, and collagen-gelatin sponge containing basic fibroblast growth factors to improve cell survival in athymic nude rats with staged skin reconstruction.
Abstract: Commercially available cultured epithelial keratinocyte sheets (KSs) have played an essential role in wound healing over the past four decades. Despite the initial uptake by the dermal elements, the survival rate of KS on the dermis-like tissue generated by conventional artificial dermis (AD) is low, making this method unsuitable for standard treatments. Therefore, an innovative AD such as collagen-gelatin sponge (CGS) that maintains the release of human recombinant basic fibroblast growth factor (bFGF) may promote wound healing. In this study, we examined whether combination therapy with KSs and CGS with bFGF (bFGF-CGS) could enhance KS survival by heterologous grafting by transplantation of human-derived KSs in an athymic nude rat wound model of staged skin reconstruction. The CGSs were implanted into skin defect wounds on athymic nude rats, which were then divided into two experimental groups: the bFGF group (CGSs containing bFGF, n = 8) and the control group (CGSs with saline, n = 8). Two weeks after implantation, human epithelial cell-derived KSs were grafted onto the dermis-like tissue, followed by assessment of the survival and morphology at 1 week later using digital imaging, histology (hematoxylin and eosin and Masson's trichrome staining), immunohistology (von Willebrand factor), immunohistochemistry (cytokeratin 1-5-6, Ki-67), and immunofluorescence (collagen IV, pan-cytokeratins) analyses. The bFGF group showed a significantly higher KS survival area (86 ± 58 mm2 vs. 32 ± 22 mm2; p < 0.05) and increased epidermal thickness (158 ± 66 μm vs. 86 ± 40 μm; p < 0.05) compared with the control group, along with higher dermis-like tissue regeneration, neovascularization, epidermal maturation, and basement membrane development. These results indicate that the survival rate of KSs in the dermis-like tissue formed by bFGF-CGS was significantly increased. Therefore, combination treatment of bFGF-CGS and KSs shows potential for full-thickness skin defect reconstruction in clinical situations. Impact statement This study highlights how using a combination of cultures, keratinocyte sheets, and collagen-gelatin sponge containing basic fibroblast growth factors can significantly improve cell survival in athymic nude rats with staged skin reconstruction. Our study makes a significant contribution to the literature because it highlights a novel and improved strategy for treating a very common condition such as skin wounds arising from many conditions. Clinical translation of this study may be useful for treating skin wounds.
2 citations
TL;DR: The numerical results demonstrated that the concentration gradients will induce the heterogeneous growth of the cells and the MTSs, which should be taken into account in designing the continuous-flow perfusion bioreactor for the cell coculture research.
Abstract: A theoretical model has been developed to investigate the microfluidic transport of the signaling chemicals in the cell coculture chips. Using an epidermal growth factor (EGF)-like growth factor as the sample chemical, the effects of velocities and channel geometry were studied for the continuous-flow microchannel bioreactors. It is found that different perfusion velocities must be applied in the parallel channels to facilitate the communication, i.e., transport of the signaling component, between the coculture channels. Such communication occurs in a unidirectional way because the signaling chemicals can only flow from the high velocity area to the low velocity area. Moreover, the effect of the transport of the signaling component between the coculture channels on the growth of the monolayer cells and the multicellular tumor spheroid (MTS) in the continuous-flow coculture environment were simulated using 3D models. The numerical results demonstrated that the concentration gradients will induce the heterogeneous growth of the cells and the MTSs, which should be taken into account in designing the continuous-flow perfusion bioreactor for the cell coculture research.
2 citations
01 Jan 2016
TL;DR: The purpose of this study was to evaluate the economic efficacy and cosmetic satisfaction of wound closure with an absorbable subcuticular stapling system, and compare these results obtained with conventional dermal sutures in breast reconstruction patients.
Abstract: Posters located in the same county as a level 1 trauma center provided 24/7 hand care. ConClusions: There is a discrepancy between emergency and elective hand care in New Jersey. Similar findings across Florida, Massachusetts, upstate New York, and Tennessee suggest a concerning trend of gaps in access to hand healthcare. As disproportionate availability between emergency and elective care lead to suboptimal patient care and unnecessary transfers, a nationwide system that can appropriately triage and treat patients is warranted. inTRoDuCTion: In abdominal based autologous breast reconstructions, abdominal closure is a time-consuming procedure. The time cost of the skin closure process is difficult to reduce. However, skin suture using absorbable sub-cuticular staples, which allow for increased rapid closure can provide equivalent healing capacity in various situations of incision closure. 1 The purpose of this study was to evaluate the economic efficacy and cosmetic satisfaction of wound closure with an absorbable subcuticular stapling system , and compare these results obtained with conventional dermal sutures in breast reconstruction patients. MATERiAls AnD METHoDs: The A total 94 patients undergoing autologous breast reconstruction were included the study. Of these, INSORB® was used in 64 patients and we compared 30 patient's clinical data as a conventional suture group. We provided a controlled surgical environment for evaluate effect of choice of closure material. For exclude the possibility of surgical procedure variety, we divide into free flap and pedicle flap groups and each group has stapler and control groups. For analysis of cost-effectivenss we applied endotracheal anesthesia expenses, and objective assessment by resident and questionnaire by patient was made for scar evaluation. REsulTs: Using paired t test, statistical analysis was made. An pedicle flap group represents 387.2hrs (stapler), 480.5hrs(control) (t-value-2.031, p-value 0.043) and free flap group represents 442.0hrs(stapler), 514.8hrs(control) (t-value-2.037, p-value 0.025) as average anesthesia time. A gap of time reduction is 93.3hrs in pedicle flap group and 72.8hrs in free flap group for absorbable stapler used groups. These reduce time of total general anesthesia in absorbable groups, which is equivalent to a 135.67$ in pedicle group and 128.35$ in free flap group. In regards to the expenses of INSORB®, only the group that used 1 stapler is significant. The complication rate, duration of healing period and the patient's satisfaction of the scar did not differ between each group. ConClusion: An absorbable staples are effective materials that allow cost-effective closure when used appropriately. While dealing with cutting-edge technology, …
2 citations
Cites background from "Fibroblast growth factors, their re..."
...FGF-2 works as a 9 fibroblast stimulus in an autocrine manner (Powers et al., 2000)....
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...9 fibroblast stimulus in an autocrine manner (Powers et al., 2000)....
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References
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TL;DR: It is demonstrated that free heparin and heparan sulfate can reconstitute a low affinity receptor that is, in turn, required for the high affinity binding of bFGF.
2,448 citations
TL;DR: This work highlights conserved protein domains that act as key regulatory participants in many of these different signalling pathways in multicellular organisms.
Abstract: Communication between cells assumes particular importance in multicellular organisms. The growth, migration and differentiation of cells in the embryo, and their organization into specific tissues, depend on signals transmitted from one cell to another. In the adult, cell signalling orchestrates normal cellular behaviour and responses to wounding and infection. The consequences of breakdowns in this signalling underlie cancer, diabetes and disorders of the immune and cardiovascular systems. Conserved protein domains that act as key regulatory participants in many of these different signalling pathways are highlighted.
2,433 citations
"Fibroblast growth factors, their re..." refers background in this paper
...One way these recruited target proteins may be localized to the activated receptor is through the interaction between their Src-homology 2 (SH2) domains and specific phosphotyrosine residues on the activated receptor (Pawson 1995)....
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...Phosphorylated tyrosine residues, in turn, recruit other signaling molecules to the activated receptors and propagate the signal through many possible transduction pathways (Pawson 1995)....
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TL;DR: Electron microscopic examination of the corneal neovascularization of thalidomide-treated rabbits revealed specific ultrastructural changes similar to those seen in the deformed limb bud vasculature of Thalidomid-treated embryos.
Abstract: Thalidomide is a potent teratogen causing dysmelia (stunted limb growth) in humans. We have demonstrated that orally administered thalidomide is an inhibitor of angiogenesis induced by basic fibroblast growth factor in a rabbit cornea micropocket assay. Experiments including the analysis of thalidomide analogs revealed that the antiangiogenic activity correlated with the teratogenicity but not with the sedative or the mild immunosuppressive properties of thalidomide. Electron microscopic examination of the corneal neovascularization of thalidomide-treated rabbits revealed specific ultrastructural changes similar to those seen in the deformed limb bud vasculature of thalidomide-treated embryos. These experiments shed light on the mechanism of thalidomide's teratogenicity and hold promise for the potential use of thalidomide as an orally administered drug for the treatment of many diverse diseases dependent on angiogenesis.
2,364 citations
TL;DR: It is demonstrated that FGF 1 is the only FGF that can activate all FGF receptor splice variants and the relative activity of all the other members of the FGF family is determined.
2,066 citations
"Fibroblast growth factors, their re..." refers background in this paper
...†From Ornitz et al. (1996), except where stated; ‡From Koga et al. (1995); §From Miralles et al. (1999); ¶From Xu et al. (1999). topologically identical to interleukin-1β (IL-1β) (Zhu et al. 1991), with which some members also share the feature of secretion by an endoplasmic reticulum…...
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...Mutation of all four cysteines to serines results in a protein with the same secondary structure and equally mitogenic for 3T3 cells as the wild-type FGF-2 (Foxet al. 1988), suggesting that the formation of disulfide bridges is not important for the secondary structure and mitogenic activity of…...
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...Ornitz et al. (1996) determined the specificity of different FGFs for different receptor isoforms by overexpressing these isoforms in Baf3 cells, which do not normally express FGFRs, and assaying for [3H]thymidine incorporation in these cells following treatment with different FGFs (see Table 2)....
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...1, IIIb 100 60 34 16 4 5 6 4 4 1, IIIc 100 104 0 102 59 55 0 1 21 2, IIIb 100 9 45 15 5 5 81 4 7 2, IIIc 100 64 4 94 25 61 2.5 16 89 3, IIIb 100 1 2 1 1 1 1 1 42 3, IIIc 100 107 1 69 12 9 1 41 96 4 100 113 6 108 7 79 2 76 75 Modified from Ornitz et al. (1996)....
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1,994 citations
"Fibroblast growth factors, their re..." refers background in this paper
...Defining features of the FGF family are a strong affinity for heparin and HLGAGs (Burgess & Maciag 1989), as well as a central core of 140 amino acids that is highly homologous between different family members....
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