PURPOSE The ectopically expressed and deregulated fibroblast growth factor receptor 3 (FGFR3) results from a t(4;14) chromosomal translocation that occurs in approximately 15% of multiple myeloma (MM) patients and confers a particularly poor prognosis. This study assesses the antimyeloma activity of CHIR-258, a small-molecule inhibitor of multiple receptor tyrosine kinases that is currently in ...

Tumor angiogenesis contributes to inferior prognosis in osteosarcoma. Apurinic/apyrimidinic endonuclease 1 (APE1) and fibroblast growth factor 2 (FGF2) and its receptor 3 (FGFR3) signaling pathway plays an important role in the angiogenic process. In this study we observed that high expression of APE1, FGF2 and FGFR3, and microvessel density are positively correlated with poor prognosis of oste...

UNLABELLED Activating mutations and/or overexpression of FGFR3 are common in bladder cancer, making FGFR3 an attractive therapeutic target in this disease. In addition, FGFR3 gene rearrangements have recently been described that define a unique subset of bladder tumors. Here, a selective HSP90 inhibitor, ganetespib, induced loss of FGFR3-TACC3 fusion protein expression and depletion of multiple...

Gain-of-function mutations in FGF receptor 3 (FGFR3) have been implicated in severe skeletal dysplasias and in a variety of cancers. In their study in this issue of the JCI, Qing et al. used specific shRNA probes to demonstrate that FGFR3 functions as an important driver of bladder carcinoma cell proliferation (see the related article beginning on page 1216). A unique anti-FGFR3 mAb was shown t...

BACKGROUND Previous evidence suggests that 25-hydroxyvitamin D(3) [25(OH)D(3)] protects against several cancers. However, little is known regarding urothelial bladder cancer (UBC). We analyzed the association between plasma 25(OH)D(3) and overall risk of UBC, as well as according to stage and FGFR3 molecular subphenotypes. METHODS Plasma concentrations of 25(OH)D(3) in 1125 cases with UBC and...

  Thanatophoricdysplasia (TD) isanosteochondrodysplasiaalwayslethalintheneonatalperiod. Thevastmajorityofcasesareduetodenovomutations. Itisdividedintotwotypes: ashortcurvedfemurcharacterizestype 1, whileastraighterfemurwithcloverleafskullcharacterizestype 2. Inthanatophoricdysplasiathelimbsareveryshort. Theribcageissmall. Thevertebralbodiesofthespinearegreatlyreducedinheightwithwidespacesbetwee...

One of the most striking aspects of the cellular pattern within the sensory epithelium of the mammalian cochlea is the presence of two rows of pillar cells in the region between the single row of inner hair cells and the first row of outer hair cells. The factors that regulate pillar cell development have not been determined; however, previous results suggested a key role for fibroblast growth ...

Endocytosis of tyrosine kinase receptors can influence both the duration and the specificity of the signal emitted. We have investigated the mechanisms of internalization of fibroblast growth factor receptor 3 (FGFR3) and compared it to that of FGFR1 which is internalized predominantly through clathrin-mediated endocytosis. Interestingly, we observed that FGFR3 was internalized at a slower rate...

Achondroplasia (ACH) is a short-limbed dwarfism resulting from gain-of-function mutations in fibroblast growth factor receptor 3 (FGFR3). Previous studies have shown that ACH patients have impaired chondrogenesis, but the effects of FGFR3 on bone formation and bone remodeling at adult stages of ACH have not been fully investigated. Using micro-computed tomography and histomorphometric analyses,...

This study aimed to determine protein expression levels of fibroblast growth factor receptors (FGFR) 1, 2 and 3 in early stage non-small cell lung cancer (NSCLC). Additionally, a screen to define the frequency of FGFR3-TACC3 translocation and FGFR3 amplification was performed. Archived tissues from 653 NSCLC samples (adenocarcinoma (AC), squamous cell carcinoma (SCC) and large cell carcinoma (L...