A Meta-Analysis of the Relationship between FGFR3 and TP53 Mutations in Bladder Cancer

TP53 and FGFR3 mutations are the most common mutations in bladder cancers. FGFR3 mutations are most frequent in low-grade low-stage tumours, whereas TP53 mutations are most frequent in high-grade high-stage tumours. Several studies have reported FGFR3 and TP53 mutations to be mutually exclusive events, whereas others have reported them to be independent. We carried out a meta-analysis of published findings for FGFR3 and TP53 mutations in bladder cancer (535 tumours, 6 publications) and additional unpublished data for 382 tumours. TP53 and FGFR3 mutations were not independent events for all tumours considered together (OR = 0.25 [0.18–0.37], p = 0.0001) or for pT1 tumours alone (OR = 0.47 [0.28–0.79], p = 0.0009). However, if the analysis was restricted to pTa tumours or to muscle-invasive tumours alone, FGFR3 and TP53 mutations were independent events (OR = 0.56 [0.23–1.36] (p = 0.12) and OR = 0.99 [0.37–2.7] (p = 0.35), respectively). After stratification of the tumours by stage and grade, no dependence was detected in the five tumour groups considered (pTaG1 and pTaG2 together, pTaG3, pT1G2, pT1G3, pT2-4). These differences in findings can be attributed to the putative existence of two different pathways of tumour progression in bladder cancer: the CIS pathway, in which FGFR3 mutations are rare, and the Ta pathway, in which FGFR3 mutations are frequent. TP53 mutations occur at the earliest stage of the CIS pathway, whereas they occur would much later in the Ta pathway, at the T1G3 or muscle-invasive stage.     

A new locus for otosclerosis, OTSC8, maps to the pericentromeric region of chromosome 9

Otosclerosis is a common disorder of the otic capsule resulting in hearing impairment in 0.3–0.4% of the Caucasian population. The aetiology of the disease remains unclear. In most cases, otosclerosis can be considered as a complex disease. In some cases, the disease is inherited as an autosomal dominant trait, sometimes with reduced penetrance. To date, seven autosomal dominant loci have been reported, but none of the disease-causing genes has been identified. In this study, we present the results of a genome-wide linkage analysis in a large Tunisian family segregating autosomal dominant otosclerosis. Linkage analysis localised the responsible gene to chromosome 9p13.1-9q21.11 with a maximal LOD score of 4.13, and this locus was named OTSC8. Using newly generated short tandem repeat polymorphism markers, we mapped this new otosclerosis locus to a 34.16 Mb interval between the markers D9S970 and D9S1799. This region comprises the pericentromeric region on both arms of chromosome 9, a highly complex region containing many duplicated sequences. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Contribution of silver nanoparticles to extend <Emphasis Type="Italic">Salmonella typhimurium</Emphasis> growth under various respiration regimes

Living cells interact with different forms of metal; the resulted biochemical alteration depends on the dose. Over an average dose in ionic form, metals interact with respiration processes at various levels, and it induces oxidative stress by shifting the whole oxydoreduction equilibrium. To correct the toxicity, cell develops different ways to cancel the effect of the exceeded charges, and it reduces the ion to get a more stable form. In the case of nanoparticles, the reactivity of surface has been enhanced that can alter the biological mechanisms; the cell may develop different strategies to minimize this reactivity. The current study is focused on the pursuing of cell behavior regarding the presence of nanoparticles and their associated metals. Nanoparticles have been synthesized using bio-reducing agents and then were structurally characterized using X-ray diffraction, UV–Vis, and infra-red spectroscopy. The oxydoreduction flexibility of the post-synthesis modified nanoparticles was tested in vitro. Interactions with cells were done using Salmonella under various respiration conditions. The final results show the possible correction of oxidative stress effects and the recuperation of respiration.     

miR-143 expression profiles in urinary bladder cancer: correlation with clinical and epidemiological parameters

Molecular Biology Reports - Hsa-mir-143 and hsa-let-7c have been reported to be deregulated in multiple neoplasms. The main purpose of this study was to investigate the expression of these miRNAs...     

Composition and intraspecific chemical variability of the essential oil from Artemisia herba-alba growing wild in a Tunisian arid zone

The intraspecific chemical variability of essential oils (50 samples) isolated from the aerial parts of Artemisia herba-alba Asso growing wild in the arid zone of Southeastern Tunisia was investigated. Analysis by GC (RI) and GC/MS allowed the identification of 54 essential oil components. The main compounds were β-thujone and α-thujone, followed by 1,8-cineole, camphor, chrysanthenone, trans-sabinyl acetate, trans-pinocarveol, and borneol. Chemometric analysis (k-means clustering and PCA) led to the partitioning into three groups. The composition of two thirds of the samples was dominated by α-thujone or β-thujone. Therefore, it could be expected that wild plants of A. herba-alba randomly harvested in the area of Kirchaou and transplanted by local farmers for the cultivation in arid zones of Southern Tunisia produce an essential oil belonging to the α-thujone/β-thujone chemotype and containing also 1,8-cineole, camphor, and trans-sabinyl acetate at appreciable amounts.     

The prevalence and prognostic significance of KRAS mutation in bladder cancer, chronic myeloid leukemia and colorectal cancer

Mutations in the KRAS gene have been shown to play a key role in the pathogenesis of a variety of human tumours. However the mutational spectrum of KRAS gene differs by organ site. In this study, we have analysed the mutational spectrum of KRAS exon 1 in bladder tumours, colorectal cancer (CRC) and chronic myeloid leukemia (CML). A total of 366 patients were included in the present study (234 bladder tumours, 48 CRC and 84 CML). The KRAS mutations are absent in BCR/ABL1 positive CML. This result suggests that BCR/ABL1 fusion gene and KRAS mutations were mutually exclusive. The frequency of KRAS mutations in bladder cancer was estimated at 4.27 %. All of mutations were found in codon 12 and 90 % of them were detected in advanced bladder tumours. However the correlation between KRAS mutations and tumour stage and grade does not report a statistical significant association. The KRAS mutations occur in 35.41 % of patients with CRC. The most frequent mutations were G12C, G12D and G13D. These mutations were significantly correlated with histological differentiation of CRC (p = 0.024). Although the high frequency of KRAS in CRC in comparison to bladder cancer, these two cancers appear to have the same mutational spectrum (p > 0.05).