5,708 research outputs found

    Chromosome 9p deletion in clear cell renal cell carcinoma predicts recurrence and survival following surgery

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    BACKGROUND: Wider clinical applications of 9p status in clear cell renal cell carcinoma (ccRCC) are limited owing to the lack of validation and consensus for interphase fluorescent in situ hybridisation (I-FISH) scoring technique. The aim of this study was to analytically validate the applicability of I-FISH in assessing 9p deletion in ccRCC and to clinically assess its long-term prognostic impact following surgical excision of ccRCC. METHODS: Tissue microarrays were constructed from 108 renal cell carcinoma (RCC) tumour paraffin blocks. Interphase fluorescent in situ hybridisation analysis was undertaken based on preset criteria by two independent observers to assess interobserver variability. 9p status in ccRCC tumours was determined and correlated to clinicopathological variables, recurrence-free survival and disease-specific survival. RESULTS: There were 80 ccRCCs with valid 9p scoring and a median follow-up of 95 months. Kappa statistic for interobserver variability was 0.71 (good agreement). 9p deletion was detected in 44% of ccRCCs. 9p loss was associated with higher stage, larger tumours, necrosis, microvascular and renal vein invasion, and higher SSIGN (stage, size, grade and necrosis) score. Patients with 9p-deleted ccRCC were at a higher risk of recurrence (P=0.008) and RCC-specific mortality (P=0.001). On multivariate analysis, 9p deletion was an independent predictor of recurrence (hazard ratio 4.323; P=0.021) and RCC-specific mortality (hazard ratio 4.603; P=0.007). The predictive accuracy of SSIGN score improved from 87.7% to 93.1% by integrating 9p status to the model (P=0.001). CONCLUSIONS: Loss of 9p is associated with aggressive ccRCC and worse prognosis in patients following surgery. Our findings independently confirm the findings of previous reports relying on I-FISH to detect 9p (CDKN2A) deletion

    Advanced Technologies for Oral Controlled Release: Cyclodextrins for oral controlled release

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    Cyclodextrins (CDs) are used in oral pharmaceutical formulations, by means of inclusion complexes formation, with the following advantages for the drugs: (1) solubility, dissolution rate, stability and bioavailability enhancement; (2) to modify the drug release site and/or time profile; and (3) to reduce or prevent gastrointestinal side effects and unpleasant smell or taste, to prevent drug-drug or drug-additive interactions, or even to convert oil and liquid drugs into microcrystalline or amorphous powders. A more recent trend focuses on the use of CDs as nanocarriers, a strategy that aims to design versatile delivery systems that can encapsulate drugs with better physicochemical properties for oral delivery. Thus, the aim of this work was to review the applications of the CDs and their hydrophilic derivatives on the solubility enhancement of poorly water soluble drugs in order to increase their dissolution rate and get immediate release, as well as their ability to control (to prolong or to delay) the release of drugs from solid dosage forms, either as complexes with the hydrophilic (e.g. as osmotic pumps) and/ or hydrophobic CDs. New controlled delivery systems based on nanotechonology carriers (nanoparticles and conjugates) have also been reviewed

    Prognostic Outcomes and Risk Factors for Patients with Renal Cell Carcinoma and Venous Tumor Thrombus after Radical Nephrectomy and Thrombectomy: The Prognostic Significance of Venous Tumor Thrombus Level.

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    IntroductionTo evaluate the prognostic outcomes and risk factors for renal cell carcinoma (RCC) patients with venous tumor thrombus in China.Materials and methodsWe reviewed the clinical information of 169 patients who underwent radical nephrectomy and thrombectomy. Overall and cancer-specific survival rates were analyzed. Univariate and multivariate analyses were used to investigate the potential prognostic factors.ResultsThe median survival time was 63 months. The five-year overall survival and cancer-specific survival rate were 53.6% and 54.4% for all patients. For all patients, significant survival difference was only observed between early (below hepatic vein) and advanced (above hepatic vein) tumor thrombus. However, significant differences existed between both RV/IVC and early/advanced tumor thrombus groups in N0M0 patients. Multivariate analysis demonstrated that higher tumor thrombus level (p = 0.016, RR = 1.58), N (p = 0.013, RR = 2.60), and M (p < 0.001, RR = 4.14) stages and adrenal gland invasion (p = 0.001, RR = 4.91) were the most significant negative prognostic predictors.ConclusionsIn this study, we reported most cases of RCC patients with venous extension in China. We proved that patients with RCC and venous tumor thrombus may have relative promising long-term survival rate, especially those with early tumor thrombus

    One Decade of Development and Evolution of MicroRNA Target Prediction Algorithms

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    Nearly two decades have passed since the publication of the first study reporting the discovery of microRNAs (miRNAs). The key role of miRNAs in post-transcriptional gene regulation led to the performance of an increasing number of studies focusing on origins, mechanisms of action and functionality of miRNAs. In order to associate each miRNA to a specific functionality it is essential to unveil the rules that govern miRNA action. Despite the fact that there has been significant improvement exposing structural characteristics of the miRNA-mRNA interaction, the entire physical mechanism is not yet fully understood. In this respect, the development of computational algorithms for miRNA target prediction becomes increasingly important. This manuscript summarizes the research done on miRNA target prediction. It describes the experimental data currently available and used in the field and presents three lines of computational approaches for target prediction. Finally, the authors put forward a number of considerations regarding current challenges and future direction

    Moral Considerations on Autopsy

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    X-ray Spectral Survey of WGACAT Quasars, II: Optical and Radio Properties of Quasars with Low Energy X-ray Cut-offs

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    We have selected quasars with X-ray colors suggestive of a low energy cut-off, from the ROSAT PSPC pointed archive. We examine the radio and optical properties of these 13 quasars. Five out of the seven quasars with good optical spectra show associated optical absorption lines, with two having high delta-v candidate systems. Two other cut-off quasars show reddening associated with the quasar. We conclude that absorption is highly likely to be the cause of the X-ray cut-offs, and that the absorbing material associated with the quasars, not intervening along the line-of-sight. The suggestion that Gigahertz Peaked Sources are associated with X-ray cut-offs remains unclear with this expanded sample.Comment: 17 pages, LaTeX, including 2 Tables and 1 figure. Ap.J. in pres
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