MicroRNAs in colorectal cancer: translation of molecular biology into clinical application

MicroRNAs (miRNAs) are small non-coding RNAs 18-25 nucleotides in length that downregulate gene expression during various crucial cell processes such as apoptosis, differentiation and development. Changes in the expression profiles of miRNAs have been observed in a variety of human tumors, including colorectal cancer (CRC). Functional studies indicate that miRNAs act as tumor suppressors and oncogenes. These findings significantly extend Vogelstein's model of CRC pathogenesis and have shown great potential for miRNAs as a novel class of therapeutic targets. Several investigations have also described the ability of miRNA expression profiles to predict prognosis and response to selected treatments in CRC patients, and support diagnosis of CRC among cancer of unknown primary site. miRNAs' occurrence has been repeatedly observed also in serum and plasma, and miRNAs as novel minimally invasive biomarkers have indicated reasonable sensitivity for CRC detection and compare favorably with the fecal occult blood test. In this review, we summarize the knowledge regarding miRNAs' functioning in CRC while emphasizing their significance in pathogenetic signaling pathways and their potential to serve as disease biomarkers and novel therapeutic targets

Expression of miRNA-106b in conventional renal cell carcinoma is a potential marker for prediction of early metastasis after nephrectomy

<p>Abstract</p> <p>Background</p> <p>MicroRNAs are endogenously expressed regulatory noncoding RNAs. Previous studies have shown altered expression levels of several microRNAs in renal cell carcinoma.</p> <p>Methods</p> <p>We examined the expression levels of selected microRNAs in 38 samples of conventional renal cell carcinoma (RCC) and 10 samples of non-tumoral renal parenchyma using TaqMan real-time PCR method.</p> <p>Results</p> <p>The expression levels of miRNA-155 (p < 0.0001), miRNA-210 (p < 0.0001), miRNA-106a (p < 0.0001) and miRNA-106b (p < 0.0001) were significantly over-expressed in tumor tissue, whereas the expression of miRNA-141 (p < 0.0001) and miRNA-200c (p < 0.0001) were significantly decreased in RCC samples. There were no significant differences between expression levels of miRNA-182 and miRNA-200b in tumor samples and renal parenchyma. Our data suggest that expression levels of miRNA-106b are significantly lower in tumors of patients who developed metastasis (p = 0.030) and miR-106b is a potential predictive marker of early metastasis after nephrectomy in RCC patients (long-rank p = 0.032).</p> <p>Conclusions</p> <p>We have confirmed previous observations obtained by miRNA microarray analysis using standardized real-time PCR method. For the first time, we have identified a prognostic significance of miRNA-106b, which, after validation on a larger group of patients, maybe useful as a promising biomarker in patients with RCC.</p

Bunecna imunoterapie nadoru. Identifikace antigen-specifickych T lymfocytu.

The thesis contains 4 publicated articles in English.Available from STL Prague, CZ / NTK - National Technical LibrarySIGLECZCzech Republi

Dynamiczna echokardiografia obciążeniowa u bezobjawowych chorych, którzy byli leczeni w dzieciństwie chemioterapią z powodu choroby nowotworowej

Background: Introducing anthracycline antibiotics into the treatment of children's malignancies contributed enormously to the excellent outcome in children and adolescents. Nevertheless, the cardiotoxicity of such was discovered as early as in the 1970's. Only recently stress tests have been used to detect late cardiotoxic effects of anti-neoplastic drugs.Aim: To determine the function of the left ventricle (LV) in asymptomatic patients who were treated with chemotherapy containing anthracyclines in childhood or adolescence.Methods: We examined 137 patients (81 men, 56 women), aged 16.6&#177;4.8 years, in whom a malignant disease was diagnosed at the age of 9.1&#177;4.8 years and who were treated with a cumulative dose of anthracyclines of 242&#177;110 mg/m2. The control group comprised 30 subjects (14 men, 16 women, mean age 19.5&#177;5.2 years). The echocardiographic examination was carried out at rest and also immediately after a dynamic stress test.Results: A decrease in the fractional shortening (FS

Stromal Vascular Fraction Cell Therapy for a Stroke Patient—Cure without Side Effects

A 48-year-old male, who suffered from a stroke resulting in cerebellum damage and occlusion of the left vertebral artery, underwent stromal vascular fraction therapy. The clinical status of the patient was monitored by a modified Stroke Specific Quality of Life Scale before therapy and at 3, 9, 12, 18, 24, and 32 months after therapy. Three months after therapy, the patient felt a reduction in pain, vertigo, and fatigue. After 9 months, he was able to walk safely on his own. After 24 months, he was able to ride a bicycle. After 32 months, he felt completely healthy without any limitations or handicaps. Therefore, intravenous application of stromal vascular fraction cells represents a promising strategy for the treatment of patients after a stroke

TiAlV/Al2O3/TiNi shape memory alloy smart composite biomaterials for orthopedic surgery

The structure and properties of TiNi/Al2O3/Ti-alloy composite implant materials consisting of a Ti-alloy body and active TiNi shape memory elements is discussed The structure of composites and ceramic/metal interfaces were evaluated by scanning electron microscopy (SEM), transmission electron microscopy (TEM), accompanied with energy and wave dispersive X-ray microanalysis (EDX, WDX). Mechanical testing of composite materials was performed using an Inova tensile/compression test machine. Bone/implant interaction and design parameters are also discussed. The structure of the TiNi alloy is modified in the casting process. Similar effects to those observed in the annealing process occurred in TiNi materials during casting and cooling of composites. The Ti-alloy matrix is composed of a mixture of α and β phases. The interaction between the ceramic layer and the metallic components depends on the cooling rate in the casting process. Different reaction products were identified on the Al2O3/metal interface with dependence on the applied cooling rate of the composite. The fatigue life of the investigated composites is greater than 10(7) cycles, and mechanical properties are sufficient to carry loads expected in human medicine. A newly developed smart implant enables quasielastic fixation with an active role of bone tissue in load carrying process, which has a positive impact on treatment