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61.
Iris Barshack Gila Lithwick-Yanai Arnon Afek Kinneret Rosenblatt Hila Tabibian-Keissar Merav Zepeniuk Lahav Cohen Harel Dan Orit Zion Yulia Strenov Sylvie Polak-Charcon Marina Perelman 《Pathology, research and practice》2010
For surgical pathologists, distinguishing whether a pulmonary neoplasm is primary or metastatic can be challenging, and current biomarkers do not always aid lung tumor classification. The tissue-associated expression of microRNA likely explains the remarkable finding that many tumors can be classified based solely on their microRNA expression signature. Here we show that microRNAs can serve as biomarkers for lung tumor classification. Using microRNA microarray data generated from 76 formalin-fixed, paraffin-embedded (FFPE) samples of either primary lung cancer or metastatic tumors to the lung, we have identified a set of microRNAs expressed differentially between these two groups. This set includes hsa-miR-182, which was most strongly over-expressed in the lung primary tumors, and hsa-miR-126, which was over-expressed in the metastatic tumors. The differential expression of this set of microRNAs was confirmed using qRT-PCR on a set of 54 samples. In light of our data, microRNA expression should be considered as a potential clinical biomarker for surgical pathologists faced with discerning the tumor type of an inscrutable lung neoplasm. 相似文献
62.
Haochang Hu Cong Zhou Bin Li Yanfei Chen Jie Dai Yiyi Mao Tianyi Huang Hang Yu Min Chen Jun Zhao Shiwei Duan 《Pathology, research and practice》2018,214(10):1572-1578
Purpose
Ras association domain family 1 isoform A (RASSF1A), a member of Ras association domain family, plays an important role in tumorigenesis. The goal of our meta-analysis was to assess the diagnostic value of RASSF1A hypermethylation in colorectal cancer (CRC).Methods
PubMed, Embase, CNKI and Wanfang databases were used to conduct literature selection. The association between RASSF1A methylation and CRC risk was evaluated by odds ratios (ORs) and 95% confidence intervals (CIs). Summary receiver operating characteristics (SROC) test was used to estimate the diagnostic value of RASSF1A methylation for CRC.Results
A total of 22 articles among 1736 CRC and 811 non-tumor samples were included in the current meta-analysis. Our results showed that RASSF1A hypermethylation was found more frequently in CRC than non-tumor samples (OR?=?6.02, 95% CI?=?4.57–7.93, P?<? 0.001). Our SROC test showed that RASSF1A hypermethylation had an area under the curve (AUC) of 0.71 with a pooled sensitivity of 0.33 (95% CI?=?0.31–0.36), a pooled specificity of 0.86 (95% CI?=?0.84–0.89), a positive-likelihood ratio of 3.18 (95% CI?=?1.99–5.09), a negative-likelihood ratio of 0.71 (95% CI?=?0.63–0.80), and a diagnostic odds ratio of 5.53 (95% CI?=?3.40–9.00). Data mining study indicated that a trend of increased RASSF1A expression was found in the CRC cell line C2C12 after 5-AZA treatment.Conclusions
Our study established that RASSF1A hypermethylation might have a potential value in the clinical diagnosis of CRC. 相似文献63.
64.
Cuneyt Tayman Ufuk Cakir Cigdem Yucel Buse Ozer Bekmez 《Archivos de bronconeumologia》2019,55(9):465-471
IntroductionEndocan levels were found to be associated with severity and mortality of the respiratory system diseases.ObjectiveWe aimed to figure out whether endocan was an important marker for the diagnosis, severity and follow-up of bronchopulmonary dysplasia (BPD).Materials and methodsInfants with moderate/severe BPD, and who required hydrocortisone treatment were included in the study group. Infants without BPD were allocated in the control group. Endocan levels were compared between the control group and the study group, and before and after the treatment in the study group.ResultsA total of 148 infants, 74 infants in the control group and 74 infants in the BPD group, were included. The endocan level was higher in the BPD group than in the control group (P = .001). Endocan levels before treatment in the BPD group was found to be higher than endocan level after treatment (P = .021).ConclusionOur study found that endocan levels increased in moderate/severe BPD. Serum endocan levels may be a safe and novel indicator for the follow-up of response to treatment and the prognosis of the severity of the disease. 相似文献
65.
66.
Serum markers detect the presence of liver fibrosis: a cohort study 总被引:47,自引:0,他引:47
Rosenberg WM Voelker M Thiel R Becka M Burt A Schuppan D Hubscher S Roskams T Pinzani M Arthur MJ;European Liver Fibrosis Group 《Gastroenterology》2004,127(6):1704-1713
BACKGROUND & AIMS: Histologic examination of a liver biopsy specimen is regarded as the reference standard for detecting liver fibrosis. Biopsy can be painful and hazardous, and assessment is subjective and prone to sampling error. We developed a panel of sensitive automated immunoassays to detect matrix constituents and mediators of matrix remodeling in serum to evaluate their performance in the detection of liver fibrosis. METHODS: In an international multicenter cohort study, serum levels of 9 surrogate markers of liver fibrosis were compared with fibrosis stage in liver biopsy specimens obtained from 1021 subjects with chronic liver disease. Discriminant analysis of a test set of samples was used to identify an algorithm combining age, hyaluronic acid, amino-terminal propeptide of type III collagen, and tissue inhibitor of matrix metalloproteinase 1 that was subsequently evaluated using a validation set of biopsy specimens and serum samples. RESULTS: The algorithm detected fibrosis (sensitivity, 90%) and accurately detected the absence of fibrosis (negative predictive value for significant fibrosis, 92%; area under the curve of a receiver operating characteristic plot, .804; standard error, .02; P < .0001; 95% confidence interval, .758-.851). Performance was excellent for alcoholic liver disease and nonalcoholic fatty liver disease. The algorithm performed equally well in comparison with each of the pathologists. In contrast, pathologists' agreement over histologic scores ranged from very good to moderate (kappa = .97-.46). CONCLUSIONS: Assessment of liver fibrosis with multiple serum markers used in combination is sensitive, specific, and reproducible, suggesting they may be used in conjunction with liver biopsy to assess a range of chronic liver diseases. 相似文献
67.
Martin Domnowski Takahiro Maruno Kanta Enomoto Felix Kummer Alina Kulakova Pernille Harris Susumu Uchiyama Jan Jaehrling Wolfgang Friess 《Journal of pharmaceutical sciences》2021,110(5):1979-1988
Attractive self-interaction processes in antibody formulations increase the risk of aggregation and extraordinarily elevated viscosity at high protein concentrations. These challenges affect manufacturing and application. This study aimed to understand the self-interaction process of Infliximab as a model system with pronounced attractive self-interaction. The association mechanism was studied by a multi-method approach comprising analytical ultracentrifugation, dynamic light scattering, small angle X-ray scattering, self-interaction bio-layer interferometry and hydrogen-deuterium exchange mass spectrometry. Based on our results, both Fab and Fc regions of Infliximab are involved in self-interaction. We hypothesize a mechanism based on electrostatic interactions of polar and charged residues within the identified areas of the heavy and the light chain of the mAb. The combination of fast and reliable screening methods and low throughput but high resolution methods can contribute to detailed characterization and deeper understanding of specific self-interaction processes. 相似文献
68.
Christine Schulze 《European journal of pharmaceutics and biopharmaceutics》2011,77(3):376-383
The alveolar lining fluid (ALF) covering the respiratory epithelium of the deep lung is the first biological barrier encountered by nanoparticles after inhalation. We here report for the first time significant differences for metal oxide nanoparticles to the binding of surfactant protein A (SP-A), the predominant protein component of ALF. SP-A is a physiologically most relevant protein and provides important biological signals. Also, it is involved in the lung’s immune defence, controlling e.g. particle binding, uptake or transcytosis by epithelial cells and macrophages. In our study, we could prove different particle-protein interaction for eight different nanoparticles, whereas particles of the same bulk material revealed different adsorption patterns. In contrast to other proteins as bovine serum albumin (BSA), SP-A does not seem to significantly deagglomerate large agglomerates of particles, indicating different adsorption mechanisms as in the well-investigated model protein BSA. These findings may have important consequences for biological fate and toxicological effects of inhaled nanomaterials. 相似文献
69.
Receiver operating characteristic (ROC) analysis plots true positive rates over false positive rates to describe the discriminatory power of a test to differentiate between two specifiable populations (that is 'normal' from 'abnormal') using a continuous dichotomous threshold. This assumes that the test separates cases into observed 'normal' or 'abnormal'. However, in practice many tests have some uninterpretable results as an inherent feature of the test itself, whether independent or dependent on the sample populations. This paper defines a method to describe the ability of tests to discriminate between specifiable populations when uninterpretable results occur non-informatively about disease status. A mixed model modified ROC curve is developed. Formulae to estimate the area under the modified ROC curve are given. Comparisons of conventional with the mixed model ROC analysis are shown in mathematical formulae as well as simulated experiments. An example of diagnosis of spinal fracture in renal transplant patients is presented. 相似文献
70.
Endrenyi Laszlo Csizmadia Ferenc Tothfalusi Laszlo Balch Alfred H. Chen Mei-Ling 《Pharmaceutical research》1998,15(3):399-404
Purpose. To determine favourable sampling conditions for assessing bioequivalence by the comparison of partial AUCs in the early phase of concentration-time profiles.
Methods. Two-period crossover trials were simulated. They assumed a wide range of the ratios of absorption rate constants of the test (T) and reference (R) formulations (kaT/kaR). Averages and standard deviations of the corresponding ratios of simulated partial AUCs (AUCpT/AUCpR) were determined together with the statistical power of assessing bioequivalence, i.e., the percentage of simulated trials in which bioequivalence was declared.
Results. The power for stating bioequivalence was high when AUCP was recorded until the earlier rather than the later of two peaks in each subject. Similarly, power was comparatively high when AUCP was measured until the time of the reference peak instead of multiples of this time. Power was high also when AUCp was determined until the fixed true, population mean time of the reference formulation instead of multiples of this time. The pattern for the kinetic sensitivity parallelled that found for the power, while the standard deviations changed generally in the opposite direction.
Conclusions. The effectiveness (power) of evaluating bioequivalence in the early phase of concentration-time profiles by partial AUCs generally decreases when the duration for measuring the metric is extended. Among the investigated designs, determination of partial AUCs until the earlier of two peaks in each subject is the most powerful. 相似文献