Abstract. BACKGROUND:Although the development of novel diagnostic and treatment strategies concerning laryngeal cancer is highly intensive, the survival rate remains virtually unchanged. Small non-coding RNAs appear to be very promising biomarkers -and so remain the focus of extensive investigation in laryngeal cancer. OBJECTIVE: We examined the expression of five miRNA and five genes related to cancer whether they could be potential laryngeal cancer biomarkers. METHODS:We performed an analysis in 47 patients diagnosed with laryngeal cancer. The qPCR technique was used to investigate the expression profile. RESULTS: While miR-21-3p and miR-525-5p were found to be significantly up-regulated, miR-139-3p and miR-885-5p expression is lower in laryngeal cancer. Moreover, PIK3R1 and HACE1 were found to be also down-regulated. CONCLUSIONS: The change in miRNA expression is frequent than the expression of other tested genes. The expression of passenger strands such as miR-21-3p and miR-139-3p, which are rarely investigated, is also significantly affected in laryngeal cancer. While PIK3R1, HACE1, miR-139-3p, and miR-885-5p may act as tumor suppressor genes in the studied tumour type, miR-21-3p and miR-525-5p seem to have oncogenic properties. Our findings suggest that miR-885-5p and PIK3R1 are the best indicators for the classification of laryngeal cancer tissue and normal mucosa.
Background The aim of the present study was to identify specific serum miRNAs (preoperative serum samples compared to healthy controls) as potential diagnostic markers for detection in laryngeal squamous cell carcinoma (LSCC). Serum samples obtained from 66 patients with LSCC were compared with 100 healthy control subjects. Additionally, miRNA levels were evaluated to identify possible correlations with clinicopathological features. Methods The expression of 377 miRNAs (screening set) was evaluated by microarray screening. The most differentially expressed miRNAs were validated by high-throughput real-time quantitative polymerase chain reaction (RT-qPCR) in the group of LSCC patients and healthy controls. Receiver-operator characteristic (ROC) curve analysis was conducted to evaluate the diagnostic accuracy of the highly and significantly identified deregulated miRNA(s) as potential candidate biomarker(s). Results According to the array analysis, eleven miRNAs revealed an altered expression profile. The levels of serum expression of miR-31, miR-141, miR-149a, miR-182, LET-7a, miR-4853p, miR-122 and miR-33 were up-regulated, and those of miR-145, miR-223 and miR-133a down-regulated, in the LSCC group compared to healthy controls. ROC curve analyses revealed an AUC (area under the ROC curve) of 1.00 (95%Cl: 0.999–1.00; P < 0.001) for miR-31 and LET-7a, 1.00 (95%Cl: 1.00–1.00; P < 0.001) for miR-33 respectively, indicating that these three miRNAs had an additive effect regarding diagnostic value. No statistically significant differences were found between the serum levels of these eleven miRNAs and the tested clinicopathological features. Conclusion Our findings outline a distinct miRNA expression profile in laryngeal cancer (LC) cases which can be used to diagnose LSCC patients with high sensitivity and specificity. Particular miRNA signatures (miR-31, LET-7a and miR-33) may be considered as novel, non-invasive biomarkers for LC diagnosis. Trial registration Registration number: RNN/203/13/KE. Date of registration 18.06.2013r.
Introduction The aim of the study was to investigate the mRNA expression and protein levels of matrix metalloproteinases (MMP) 2 (MMP-2), 9 (MMP-9), 7 (MMP-7) and their tissue inhibitor TIMP-2 in patients with laryngeal squamous cell carcinoma and control subjects and additionally to evaluate a possible correlation with clinicopathological features. Material and methods The expression levels of MMP-2, MMP-9, MMP-7, and TIMP-2 mRNA were detected by the real-time quantitative real time polymerase chain reaction method in 96 cases of laryngeal carcinoma vs. non-tumor tissue. The blood serum levels of MMP-2, MMP-9, MMP-7, and TIMP-2 in patients with laryngeal cancer and 100 healthy subjects were measured using the enzyme-linked immunosorbent assay (ELISA) method. Results The present study demonstrated that MMP-2, MMP-7, MMP-9 and TIMP-2 mRNA expression levels in carcinoma tissue vs. non-tumor tissue and protein levels in the preoperative serum vs. those obtained in healthy controls were statistically significantly higher than in the healthy controls ( p = 0.001). The only significant correlation between mRNA or concentration of measured MMPs and TIMP and the clinicopathological features was found for TIMP-2 protein and for patients with lymph node metastasis. Serum levels of TIMP-2 were higher in cases with lymph node metastasis than in those without lymph node metastasis ( p < 0.05). Conclusions The results may suggest that MMPs and TIMP-2 are associated with laryngeal tumorigenesis, but we did not find any distinct correlation between the clinicopathological features of laryngeal squamous cell carcinoma patients and expression levels of MMPs and TIMP. The results suggest that the measurement of serum MMP-2, MMP-7, MMP-9 and TIMP-2 concentration might be helpful to diagnose laryngeal squamous cell carcinoma.
This review summarizes current knowledge about the occurrence of hearing and balance disorders after antimalarial drugs treatment. It also examines the clinical applications of antimalarials, their mechanisms behind this ototoxicity and how it can be monitored. It includes studies with larger numbers of patients and those in which auditory function was assessed using audiological tests. Some antimalarials have been repurposed for other conditions like autoimmune disorders, rheumatic diseases, some viral diseases and cancers. While old antimalarial drugs, such as quinoline derivatives, are known to demonstrate ototoxicity, a number of new synthetic antimalarial agents particularly artemisinin derivatives, demonstrate unknown ototoxicity. Adverse audiovestibular effects vary depending on the medication itself, its dose and route of administration, as well as the drug combination, treated disease and individual predispositions of the patient. Dizziness was commonly reported, while vestibular symptoms, hearing loss and tinnitus were observed much less frequently, and most of these symptoms were reversible. As early identification of ototoxic hearing loss is critical to introducing possible alternative treatments with less ototoxic medications, therefore monitoring systems of those drugs ototoxic side effects are much needed.
Introduction.To investigate the mRNA and protein expression of MMP-2, MMP-9, MMP-7 and their tissue inhibitor TIMP-2 in tissue specimens with oral squamous cell cancer (OSCC) and in healthy tissues. Material and methods. The expression genes of MMP-2, MMP-9, MMP-7 and TIMP-2 on mRNA levels were detected by the RT-PCR method in 31 samples with oral squamous cell carcinoma and in 31 healthy, control tissues. Secondly, the concentration of the analysed metalloproteinases and their inhibitor was assessed in tumor and non-tumor tissues using the enzyme-linked immunosorbent assay (ELISA) method. Results. The mean values of gene expression of MMP-2, MMP-7, MMP-9 and TIMP in tissues with oral squamous cell cancer were significantly higher in comparison to normal ones (p < 0.0001). Similar observations were found for concentration levels of analysed MMPs and TIMP in tissues with and without oral cancer (p < 0.0001).Conclusions. The present study demonstrated that MMP-2, MMP-7, MMP-9 and TIMP-2 gene expression on protein and mRNA levels is higher in oral squamous cell carcinoma tissues than in healthy control tissues. This may suggest that MMPs and TIMP play an important role in tumorogenesis. We did not observe any correlation between the clinicopathological characteristics of patients with OSCC and expression levels of MMPs and TIMP.
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