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71.
Yabin Cheng Jing Lu Guangdi Chen Gholamreza Safaee Ardekani Anand Rotte Magdalena Martinka Xuezhu Xu Kevin J. McElwee Guohong Zhang Youwen Zhou 《Oncotarget》2015,6(6):4180-4189
The melanoma staging system proposed by the American Joint Committee on Cancer (AJCC) (which classifies melanoma patients into four clinical stages) is currently the most widely used tool for melanoma prognostication, and clinical management decision making by clinicians. However, multiple studies have shown that melanomas within specific AJCC Stages can exhibit varying progression and clinical outcomes. Thus, additional information, such as that provided by biomarkers is needed to assist in identifying the patients at risk of disease progression.Having previously found six independent prognostic biomarkers in melanoma, including BRAF, MMP2, p27, Dicer, Fbw7 and Tip60, our group has gone on to investigate if these markers are useful in risk stratification of melanoma patients in individual AJCC stages. First, we performed Kaplan-Meier survival and Cox proportional multivariate analyses comparing prognostication power of these markers in 254 melanoma patients for whom the expression levels were known, identifying the best performing markers as candidates for stage-specific melanoma markers. We then verified the results by incorporating an additional independent cohort (87 patients) and in a combined cohort (341 patients).Our data indicate that BRAF and MMP2 are optimal prognostic biomarkers for AJCC Stages I and II, respectively (P = 0.010, 0.000, Log-rank test); whereas p27 emerged as a good marker for AJCC Stages III/IV (0.018, 0.046, respectively, log-rank test). Thus, our study has identified stage-specific biomarkers in melanoma, a finding which may assist clinicians in designing improved personalized therapeutic modalities. 相似文献
72.
Venkatesh Pilla Reddy Magdalena Kozielska Rik de Greef An Vermeulen Johannes H. Proost 《Journal of pharmacokinetics and pharmacodynamics》2013,40(3):377-388
High and variable placebo effect (PE) within and among clinical trials can substantially affect conclusions about the efficacy of new drugs in the treatment of schizophrenia and other neuropsychiatric disorders. In recent years, it has become increasingly difficult to prove drug efficacy against placebo, and one of the reasons is that the placebo response has increased over recent years. The increased placebo response over the years is partly explained by unidentified parallel interventions, patient factors, issues with trial designs, and regional variability or demographic differences. In addition, a nocebo effect, which is undesirable effects a subject manifests after receiving placebo, e.g. extrapyramidal side effects, in placebo arms of antipsychotic trials could also influence the PE and clinical trial outcomes. Placebo effects (PEs) are a natural phenomenon and cannot be avoided completely in clinical trials. However, accounting for the PE via mixed effects modelling approaches could reduce bias in quantifying the overall effect size of the drug treatment. This review article focuses on the PE and its impact on schizophrenia clinical trial outcomes. The authors briefly describe the factors that lead to high and variable PE. Next, pharmacometric approaches to account for the PE and dropouts in schizophrenia clinical trials are described. Finally, some points are provided that could be considered while designing and optimizing antipsychotic trials via simulation approaches. 相似文献
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Magdalena Groblewska Barbara Mroczko Mariusz Gryko Anna Pryczynicz Katarzyna Guzińska-Ustymowicz Bogusław Kędra Andrzej Kemona Maciej Szmitkowski 《Tumour biology》2014,35(4):3793-3802
The objective of the study was the assessment of serum levels and tissue expression of matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of matrix metalloproteinases 2 (TIMP-2) in patients with colorectal cancer (CRC). The study included 72 CRC patients and 68 healthy subjects. The serum levels of MMP-2 and TIMP-2 were measured using enzyme-linked immunosorbent assay (ELISA) method, whereas tissue expression of MMP-2 and TIMP-2 in cancer cells, interstitial inflammatory cells, and adjacent normal colorectal mucosa were examined by immunohistochemical staining of tumor samples. The serum levels of MMP-2 and TIMP-2 in cancer patients were significantly lower than those in control group, but the percentage of positive immunoreactivity of these proteins were higher in malignant and inflammatory cells as compared to normal tissue. There was a significant correlation between MMP-2 immunoreactivity in inflammatory cells and the presence of distant metastases and between TIMP-2 expression in inflammatory cells and tumor size, nodal involvement, and distant metastases. Area under receiver operating characteristic (ROC) curve (AUC) for serum MMP-2 was higher than for serum TIMP-2. Moreover, positive tissue expression of MMP-2 was a significant prognostic factor for CRC patients’ survival. Our findings suggest that MMP-2 and TIMP-2 might play a role in the process of colorectal cancer invasion and metastasis, but the significance of their interactions with tumor stroma and interstitial inflammatory infiltration in colorectal neoplasia require further elucidation. 相似文献
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Olfaction in patients with allergic rhinitis: an indicator of successful MP‐AzeFlu therapy 下载免费PDF全文
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Anna Brillowska‐Dąbrowska Magdalena Wianecka Sławomir Dąbrowski Zuzana Mladenovska Józef Kur Birgitte K. Ahring 《Scandinavian journal of clinical and laboratory investigation》2013,73(8):720-730
A DNA fingerprinting method known as ALIS‐FLP (amplified ligation selected fragment‐length polymorphism) has been developed for selective and specific amplification of restriction fragments from TspRI restriction endonuclease digested genomic DNA. The method is similar to AFLP, but differs in that only one specific restriction enzyme (TspRI) is used. The cohesive ends of the DNA fragments are ligated with two types of oligonucleotide. A long oligonucleotide containing the primer site and the specific 9 nt 3 prime end, which is complementary to specific 9 nt, cohesive 3 prime end of the TspRI genomic DNA fragment, and a short, degenerated, oligonucleotide covering the remaining TspRI cohesive ends. Other cohesive ends are covered by a short degenerated oligonucleotide lacking the primer site. The ligation mixture is used as a template for amplification using a single primer corresponding to the 5 prime end of the long, specific oligonucleotide. The selection of TspRI digested genomic DNA fragments for amplification is achieved by sequence selective ligation of the specific long oligonucleotide carrying the primer site to both ends of the specific target fragment. This technique allows for differentiation of the organisms without previous knowledge of their DNA sequence. The usefulness of the method is confirmed by genotyping of 70 previously characterized clinical E. coli isolates. The grouping obtained was identical to the results of REA‐PFGE. Versatility of the method is highlighted, i.e. its combining the advantages of the AFLP technique with a simple, rapid and cheap polymerase chain reaction product detection method. 相似文献
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