131 research outputs found
Induction Chemotherapy Followed by Concurrent Chemoradiation Therapy Versus Concurrent Chemoradiation Therapy Upfront in Locally Advanced Oral Cavity Cancer: Systematic Review and Meta-Analysis of Individual Data
Univ Sao Paulo, Hosp Siriolibanes, Dept Radiat Oncol, Sao Paulo, BrazilUniv Sao Paulo, Fac Med, Inst Canc Estado Sao Paulo, Sao Paulo, BrazilUniv Fed Sao Paulo, Escola Paulista Med UNIFESP EPM, Brazilian Cochrane Ctr, Sao Paulo, BrazilUniv Fed Sao Paulo, Escola Paulista Med UNIFESP EPM, Discipline Emergency Med & Evidence Based Med, Sao Paulo, BrazilHarvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USABrigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USAUniv Calif San Diego, La Jolla, CA 92093 USAHarvard Univ, Sch Med, Dana Farber Canc Inst, Head & Neck Oncol Program, 44 Binney St, Boston, MA 02115 USAAC Camargo Canc Ctr, Dept Head & Neck Surg & Otorhinolaryngol, Sao Paulo, BrazilUniv Fed Sao Paulo, Escola Paulista Med UNIFESP EPM, Brazilian Cochrane Ctr, Sao Paulo, BrazilUniv Fed Sao Paulo, Escola Paulista Med UNIFESP EPM, Discipline Emergency Med & Evidence Based Med, Sao Paulo, BrazilWeb of Scienc
Circulating Antinuclear Antibodies in Patients with Pelvic Masses Are Associated with Malignancy and Decreased Survival
BACKGROUND: Circulating autoantibodies occur more frequently in cancer patients than in patients without cancer. METHODS AND FINDINGS: We examined sera from patients referred for pelvic mass symptoms to a tertiary university clinic. A total of 127 were diagnosed with epithelial ovarian cancer while 386 had a benign condition. A screen for IgG anti-nuclear antibodies (ANA) by indirect immunofluorescence on HEp-2 cells confirmed a highly significant overrepresentation of ANA in the cancer group where 40% had detectable (i.e., a titer ≥160) ANA compared with less than 12% in the benign group. The overrepresentation of ANA in the cancer group persisted (p<0.0001) after matching the age-profile of the benign group with the ovarian cancer group. Only 19 out of 127 patients in the age-matched benign subgroup were positive for ANA corresponding to an 85% specificity at 40% sensitivity of ANA as the only marker for malignancy. No correlation of ANA positivity in either group with specific bands in immunoblots could be demonstrated even though immunoblot positivity was clearly increased in the malignant group (41% vs. 3%). The presence, strength, and type of ANA did not correlate with serum CA-125 values or with staging, and ANA outcome did not contribute with independent diagnostic information. However, survival was significantly shorter in ANA-positive compared with ANA-negative cancer patients and patients with CA-125 below the median CA-125 value in the cancer group had a significantly decreased survival when positive for ANA. ANA status made no difference in the group with CA-125 values above the median. Also, there was a significant correlation between speckled ANA-strength and histological tumor grade. CONCLUSIONS: Circulating antibodies are a promising source for new biomarkers in cancer. Characterization of epitope specificities and measurements of consecutive samples will be important for further elucidating the role of ANA in evaluating ovarian cancer patients
Evaluation of two commercial global miRNA expression profiling platforms for detection of less abundant miRNAs
<p>Abstract</p> <p>Background</p> <p>microRNAs (miRNA) are short, endogenous transcripts that negatively regulate the expression of specific mRNA targets. miRNAs are found both in tissues and body fluids such as plasma. A major perspective for the use of miRNAs in the clinical setting is as diagnostic plasma markers for neoplasia. While miRNAs are abundant in tissues, they are often scarce in plasma. For quantification of miRNA in plasma it is therefore of importance to use a platform with high sensitivity and linear performance in the low concentration range. This motivated us to evaluate the performance of three commonly used commercial miRNA quantification platforms: GeneChip miRNA 2.0 Array, miRCURY Ready-to-Use PCR, Human panel I+II V1.M, and TaqMan Human MicroRNA Array v3.0.</p> <p>Results</p> <p>Using synthetic miRNA samples and plasma RNA samples spiked with different ratios of 174 synthetic miRNAs we assessed the performance characteristics reproducibility, recovery, specificity, sensitivity and linearity. It was found that while the qRT-PCR based platforms were sufficiently sensitive to reproducibly detect miRNAs at the abundance levels found in human plasma, the array based platform was not. At high miRNA levels both qRT-PCR based platforms performed well in terms of specificity, reproducibility and recovery. At low miRNA levels, as in plasma, the miRCURY platform showed better sensitivity and linearity than the TaqMan platform.</p> <p>Conclusion</p> <p>For profiling clinical samples with low miRNA abundance, such as plasma samples, the miRCURY platform with its better sensitivity and linearity would probably be superior.</p
Identification of lung cancer gene markers through kernel maximum mean discrepancy and information entropy
© 2019 The Author(s). Background: The early diagnosis of lung cancer has been a critical problem in clinical practice for a long time and identifying differentially expressed gene as disease marker is a promising solution. However, the most existing gene differential expression analysis (DEA) methods have two main drawbacks: First, these methods are based on fixed statistical hypotheses and not always effective; Second, these methods can not identify a certain expression level boundary when there is no obvious expression level gap between control and experiment groups. Methods: This paper proposed a novel approach to identify marker genes and gene expression level boundary for lung cancer. By calculating a kernel maximum mean discrepancy, our method can evaluate the expression differences between normal, normal adjacent to tumor (NAT) and tumor samples. For the potential marker genes, the expression level boundaries among different groups are defined with the information entropy method. Results: Compared with two conventional methods t-test and fold change, the top average ranked genes selected by our method can achieve better performance under all metrics in the 10-fold cross-validation. Then GO and KEGG enrichment analysis are conducted to explore the biological function of the top 100 ranked genes. At last, we choose the top 10 average ranked genes as lung cancer markers and their expression boundaries are calculated and reported. Conclusion: The proposed approach is effective to identify gene markers for lung cancer diagnosis. It is not only more accurate than conventional DEA methods but also provides a reliable method to identify the gene expression level boundaries
Haemolysis during Sample Preparation Alters microRNA Content of Plasma
The presence of cell-free microRNAs (miRNAs) has been detected in a range of body fluids. The miRNA content of plasma/serum in particular has been proposed as a potential source of novel biomarkers for a number of diseases. Nevertheless, the quantification of miRNAs from plasma or serum is made difficult due to inefficient isolation and lack of consensus regarding the optimal reference miRNA. The effect of haemolysis on the quantification and normalisation of miRNAs in plasma has not been investigated in great detail. We found that levels of miR-16, a commonly used reference gene, showed little variation when measured in plasma samples from healthy volunteers or patients with malignant mesothelioma or coronary artery disease. Including samples with evidence of haemolysis led to variation in miR-16 levels and consequently decreased its ability to serve as a reference. The levels of miR-16 and miR-451, both present in significant levels in red blood cells, were proportional to the degree of haemolysis. Measurements of the level of these miRNAs in whole blood, plasma, red blood cells and peripheral blood mononuclear cells revealed that the miRNA content of red blood cells represents the major source of variation in miR-16 and miR-451 levels measured in plasma. Adding lysed red blood cells to non-haemolysed plasma allowed a cut-off level of free haemoglobin to be determined, below which miR-16 and miR-451 levels displayed little variation between individuals. In conclusion, increases in plasma miR-16 and miR-451 are caused by haemolysis. In the absence of haemolysis the levels of both miR-16 and miR-451 are sufficiently constant to serve as normalisers
Let-7 MicroRNA Family Is Selectively Secreted into the Extracellular Environment via Exosomes in a Metastatic Gastric Cancer Cell Line
Background: Exosomes play a major role in cell-to-cell communication, targeting cells to transfer exosomal molecules including proteins, mRNAs, and microRNAs (miRNAs) by an endocytosis-like pathway. miRNAs are small noncoding RNA molecules on average 22 nucleotides in length that regulate numerous biological processes including cancer pathogenesis and mediate gene downregulation by targeting mRNAs to induce RNA degradation and/or interfering with translation. Recent reports imply that miRNAs can be stably detected in circulating plasma and serum since miRNAs are packaged by exosomes to be protected from RNA degradation. Thus, profiling exosomal miRNAs are in need to clarify intercellular signaling and discover a novel disease marker as well. Methodology/Principal Findings: Exosomes were isolated from cultured cancer cell lines and their quality was validated by analyses of transmission electron microscopy and western blotting. One of the cell lines tested, a metastatic gastric cancer cell line, AZ-P7a, showed the highest RNA yield in the released exosomes and distinctive shape in morphology. In addition, RNAs were isolated from cells and culture media, and profiles of these three miRNA fractions were obtained using microarray analysis. By comparing signal intensities of microarray data and the following validation using RT-PCR analysis, we found that let-7 miRNA family was abundant in both the intracellular and extracellular fractions from AZ-P7a cells, while low metastatic AZ-521, the parental cell line of AZ-P7a, as well as other cancer cell lines showed no such propensity. Conclusions/Significance: The enrichment of let-7 miRNA family in the extracellular fractions, particularly, in the exosome
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