Up-regulation and co-expression of fibroblast growth factor receptors in human gastric cancer

2000 ◽  
Vol 126 (9) ◽  
pp. 519-528 ◽  
Author(s):  
Eun-Young Shin ◽  
Bin-Ho Lee ◽  
Jong-Ho Yang ◽  
Kyeong-Sun Shin ◽  
Geon-Kook Lee ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Growth Factor Receptors ◽  
Human Gastric Cancer ◽  
Fibroblast Growth ◽  
Fibroblast Growth Factor Receptors

scholarly journals Therapeutic Targeting of Fibroblast Growth Factor Receptors in Gastric Cancer

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Mikito Inokuchi ◽  
Yoshitaka Fujimori ◽  
Sho Otsuki ◽  
Yuya Sato ◽  
Masatoshi Nakagawa ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Growth Factor ◽  
Tyrosine Kinase ◽  
Signaling Pathways ◽  
Fibroblast Growth Factor ◽  
Growth Factor Receptor ◽  
Growth Factor Receptors ◽  
Fibroblast Growth ◽  
Fibroblast Growth Factor Receptors ◽  
Genomic Amplification

Chemotherapy has become the global standard treatment for patients with metastatic or unresectable gastric cancer (GC), although outcomes remain unfavorable. Many molecular-targeted therapies inhibiting signaling pathways of various tyrosine kinase receptors have been developed, and monoclonal antibodies targeting human epidermal growth factor receptor 2 (HER2) have become standard therapy for HER2-positive GC. An inhibitor of vascular endothelial growth factor receptor 2 or MET has also produced promising results in patients with GC. Fibroblast growth factor receptors (FGFR) play key roles in tumor growth via activated signaling pathways in GC. Genomic amplification of FGFR2 leads to the aberrant activation found in GC tumors and is related to survival in patients with GC. This review discusses the clinical relevance of FGFR in GC and examines FGFR as a potential therapeutic target in patients with GC. Preclinical studies in animal models suggest that multitargeted tyrosine kinase inhibitors (TKIs), including FGFR inhibitor, suppress tumor cell proliferation and delay tumor progression. Several TKIs are now being evaluated in clinical trials as treatment for metastatic or unresectable GC harboring FGFR2 amplification.

scholarly journals Prognostic significance of the co-overexpression of fibroblast growth factor receptors 1, 2 and 4 in gastric cancer

2014 ◽  
Vol 2 (4) ◽  
pp. 509-517 ◽  
Author(s):  
HIDEAKI MURASE ◽  
MIKITO INOKUCHI ◽  
YOKO TAKAGI ◽  
KEIJI KATO ◽  
KAZUYUKI KOJIMA ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Prognostic Significance ◽  
Growth Factor Receptors ◽  
Fibroblast Growth ◽  
Fibroblast Growth Factor Receptors

scholarly journals Targeting fibroblast growth factor receptors to combat aggressive ependymoma

2021 ◽  
Author(s):  
Daniela Lötsch ◽  
Dominik Kirchhofer ◽  
Bernhard Englinger ◽  
Li Jiang ◽  
Konstantin Okonechnikov ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Molecular Mechanisms ◽  
Radial Glia ◽  
Growth Factor Receptors ◽  
Dominant Negative ◽  
Mrna Levels ◽  
Fibroblast Growth ◽  
Cell Models ◽  
Fibroblast Growth Factor Receptors

AbstractEpendymomas (EPN) are central nervous system tumors comprising both aggressive and more benign molecular subtypes. However, therapy of the high-risk subtypes posterior fossa group A (PF-A) and supratentorial RELA-fusion positive (ST-RELA) is limited to gross total resection and radiotherapy, as effective systemic treatment concepts are still lacking. We have recently described fibroblast growth factor receptors 1 and 3 (FGFR1/FGFR3) as oncogenic drivers of EPN. However, the underlying molecular mechanisms and their potential as therapeutic targets have not yet been investigated in detail. Making use of transcriptomic data across 467 EPN tissues, we found that FGFR1 and FGFR3 were both widely expressed across all molecular groups. FGFR3 mRNA levels were enriched in ST-RELA showing the highest expression among EPN as well as other brain tumors. We further identified high expression levels of fibroblast growth factor 1 and 2 (FGF1, FGF2) across all EPN subtypes while FGF9 was elevated in ST-EPN. Interrogation of our EPN single-cell RNA-sequencing data revealed that FGFR3 was further enriched in cycling and progenitor-like cell populations. Corroboratively, we found FGFR3 to be predominantly expressed in radial glia cells in both mouse embryonal and human brain datasets. Moreover, we detected alternative splicing of the FGFR1/3-IIIc variant, which is known to enhance ligand affinity and FGFR signaling. Dominant-negative interruption of FGFR1/3 activation in PF-A and ST-RELA cell models demonstrated inhibition of key oncogenic pathways leading to reduced cell growth and stem cell characteristics. To explore the feasibility of therapeutically targeting FGFR, we tested a panel of FGFR inhibitors in 12 patient-derived EPN cell models revealing sensitivity in the low-micromolar to nano-molar range. Finally, we gain the first clinical evidence for the activity of the FGFR inhibitor nintedanib in the treatment of a patient with recurrent ST-RELA. Together, these preclinical and clinical data suggest FGFR inhibition as a novel and feasible approach to combat aggressive EPN.

Semirational design of a potent, artificial agonist of fibroblast growth factor receptors

10.1038/70746 ◽  
1999 ◽  
Vol 17 (12) ◽  
pp. 1199-1204 ◽  
Author(s):  
Marcus D. Ballinger ◽  
Venkatakrishna Shyamala ◽  
Louise D. Forrest ◽  
Maja Deuter-Reinhard ◽  
Laura V. Doyle ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Growth Factor Receptors ◽  
Fibroblast Growth ◽  
Fibroblast Growth Factor Receptors

scholarly journals Role of Klotho in Hyperglycemia: Its Levels and Effects on Fibroblast Growth Factor Receptors, Glycolysis, and Glomerular Filtration

2021 ◽  
Vol 22 (15) ◽  
pp. 7867
Author(s):  
Marlena Typiak ◽  
Tomasz Kulesza ◽  
Patrycja Rachubik ◽  
Dorota Rogacka ◽  
Irena Audzeyenka ◽  
...  
Keyword(s):  
Growth Factor ◽  
Urinary Excretion ◽  
Glomerular Filtration ◽  
Fibroblast Growth Factor ◽  
Growth Factor Receptors ◽  
Renal Tissue ◽  
Proper Function ◽  
Fibroblast Growth ◽  
Fibroblast Growth Factor Receptors ◽  
Plasma Filtration

Hyperglycemic conditions (HG), at early stages of diabetic nephropathy (DN), cause a decrease in podocyte numbers and an aberration of their function as key cells for glomerular plasma filtration. Klotho protein was shown to overcome some negative effects of hyperglycemia. Klotho is also a coreceptor for fibroblast growth factor receptors (FGFRs), the signaling of which, together with a proper rate of glycolysis in podocytes, is needed for a proper function of the glomerular filtration barrier. Therefore, we measured levels of Klotho in renal tissue, serum, and urine shortly after DN induction. We investigated whether it influences levels of FGFRs, rates of glycolysis in podocytes, and albumin permeability. During hyperglycemia, the level of membrane-bound Klotho in renal tissue decreased, with an increase in the shedding of soluble Klotho, its higher presence in serum, and lower urinary excretion. The addition of Klotho increased FGFR levels, especially FGFR1/FGFR2, after their HG-induced decrease. Klotho also increased levels of glycolytic parameters of podocytes, and decreased podocytic and glomerular albumin permeability in HG. Thus, we found that the decrease in the urinary excretion of Klotho might be an early biomarker of DN and that Klotho administration may have several beneficial effects on renal function in DN.

Mapping of Murine Fibroblast Growth Factor Receptors Refines Regions of Homology between Mouse and Human Chromosomes

Genomics ◽  
1994 ◽  
Vol 21 (3) ◽  
pp. 656-658 ◽  
Author(s):  
Karen B. Avraham ◽  
David Givol ◽  
Aaron Avivi ◽  
Avner Yayon ◽  
Neal G. Copeland ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Growth Factor Receptors ◽  
Fibroblast Growth ◽  
Human Chromosomes ◽  
Fibroblast Growth Factor Receptors ◽  
Murine Fibroblast
Sign in / Sign up

Export Citation Format

Share Document