Synthesis and cancer cell growth inhibitory activity of icaritin derivatives

Article abstract of DOI:10.1016/j.ejmech.2015.06.006

Abstract A series of icaritin derivatives bearing carboxylic acid or carboxylic ester groups are synthesized, and their in vitro cytotoxic activity against three cancer cell lines, MCF-7, MDA-MB-435s, and A549, are evaluated by MTT assay. Several derivati

Full text of DOI:10.1016/j.ejmech.2015.06.006

Detection of FGFR3 mutations from urine sediment DNA to predict the risk of intravesical
recurrence after radical nephroureterectomy for upper tract urothelial carcinoma
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Eur Urol Suppl 2015;14/2;e1056
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Seisen T. , Rouprêt M. , Cancel-Tassin G. , Léon P. , Compérat E. , Drouin S. , Phé V. , Renard-Penna R. , Mozer P. , Cussenot O.
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Hopital Pitié - Salpêtrière, Dept. of Urology, Paris, France, Hopital Pitié - Salpêtrière, Dept. of Cancer Research, Paris, France, Hopital
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Pitié - Salpêtrière, Dept. of Pathology, Paris, France, Hopital Pitié - Salpêtrière, Dept. of Radiology, Paris, France
INTRODUCTION & OBJECTIVES: To assess the role of FGFR3 mutations, detected from urine sediment DNA, in intravesical recurrence
(IVR) after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC).
MATERIAL & METHODS: Freshly voided urine samples were obtained from 46 patients before undergoing RNU to treat UTUC. DNA was
extracted from urine sediments to perform allele-specific PCR assays for the detection of R248C, S249C, G372C and Y375C mutations.
Kaplan Meier method and log-rank test have been used to analyse IVR-free survival according to FGFR-3 status. Univariate and
multivariate Cox regression analyses have been conducted to determine predictors of IVR.
RESULTS: Overall, FGFR3 mutations occurred in 21 (46%) patients. The mutation in codon 249 was the most frequent (13/61%), followed
by Y375C (4/19%), R248C (2/10%) and G372C (2/10%). Patients with FGFR3 mutations were more likely to develop ureteral (57% vs 40%;
p=0.04) superficial (81% vs 52%; p=0.04), low-grade (67% vs 8%; p<0.001) tumours without concomitant CIS (10% vs 40%; p<0.001) or
lymphovascular invasion (5% vs 60% ; p<0.001). An IVR was diagnosed in 13 (28%) patients within a median time of 19.9 [15-27] months.
The incidence of IVR was significantly greater in patients with FGFR3 mutations (43% vs 16%; p=0,04). The five-years IVR-free survival
rates were 52% and 82% in wild type and mutant patients, respectively (p=0,12) (Figure 1). In multivariate analysis, current smocker status
(HR=2.42; p=0.006), previous bladder cancer (HR=2.14; p<0.001), positive pre-operative urinary cytology (HR=2.25; p<0.001), ureteral
tumour location (HR=1.55; p=0.002), multifocality (HR=2.69; p<0.001), invasive pT stage (HR=1.78; p=0.004) were significantly correlated
to IVR. However, FGFR3 mutations were not an independent predictor of IVR (HR=2,39; p=0,09).

CONCLUSIONS: We found clinical evidence that supported the general idea that both the intra-luminal seeding of a single transformed cell
and the pan-urothelial field defect mechanisms are deeply involved with IVR after RNU. Furthermore, although FGFR3 mutations were not
an independent predictor of IVR, there was an increased risk for developing a bladder cancer after RNU in FGFR3 mutant patients.