Ondrej Topolcan

Relevance of miR-21 and miR-143 expression in tissue samples of colorectal carcinoma and its liver metastases

MicroRNAs, which are endogenously expressed regulatory noncoding RNAs, have an altered expression in colorectal cancer. The aim of our study was to assess the relationship of miR-21 and miR-143 expression to the prognostic/clinicopathological features of colorectal carcinoma (CRC) and colorectal liver metastases (CLM). The estimation was performed in 46 paired (tumor and control) tissue samples of CRC. Further, we studied 30 tissue samples of CLM. MiR-21 and miR-143 expressions were quantified by using the quantitative reverse transcription polymerase chain reaction method. Relation of miR-21 and miR-143 expression to disease-free interval (DFI) (Wilcoxon; P = 0.0026 and P = 0.0191, respectively) was recorded. There was shorter DFI in patients with a higher expression of miR-21 and, surprisingly, also in patients with a higher expression of miR-143, which is a putative tumor suppressor. There was a higher expression of miR-21 and lower expression of miR-143 in CRC tissue in comparison with adjacent normal colon tissue (P < 0.0001; P < 0.0001, respectively). Similarly, we observed a higher expression of miR-21 and a lower expression of miR-143 in CLM in comparison with normal colon tissue (P < 0.0001; P < 0.0001, respectively). Our results support the hypothesis about oncogenic function of miR-21 and show its relation to DFI. The role of miR-143 in carcinogenesis seems to be more complex.

Inflammation in the wall of abdominal aortic aneurysm and its role in the symptomatology of aneurysm.

Cytosol levels of cytokines [interleukins 1b, 6, 8 (IL-1b, 6, 8), tumor necrosis factor-alpha (TNF-alpha)] in aneurysm walls were evaluated in a prospective non-randomized study of 57 patients. The group was divided into two subgroups: Subgroup I (ruptured aneurysms, n=11) and Subgroup II (asymptomatic aneurysms, n=32). A control group consisted of 14 kidney donors. Aortic walls were examined by immunohistochemistry and microscopy to detect inflammatory cells. More pronounced inflammatory changes and higher cytosol cytokine levels [IL6 (p<0.001), IL8 (p<0.0003) and TNFalpha (p<0.002)] were found in the walls of ruptured aneurysms than in the asymptomatic aneurysms. Immunohistochemically, most cells within the inflammatory infiltrates stained positively with the monoclonal antibody to the leucocyte common antigen (CD 45). The majority were of B-cell origin, which was demonstrated by positive staining with the monoclonal antibody L26 directed against the CD 20 antigen. These results show that an inflammatory process plays a significant role in patients with ruptured abdominal aortic aneurysms (AAA). A means of modifying the inflammatory process in the wall of AAAs might play an important role in preventing aneurysm rupture.

The role of thymidine kinase in cancer diseases

Thymidine kinase 1 (TK 1-fetal) is a cell cycle-dependent marker that increases dramatically during the S-phase of the cell cycle. In this review, the authors discuss serum levels of thymidine kinase in a variety of neoplasias. Determination of thymidine kinase helps to monitor the follow-up of solid tumours and haematological malignancies as well as indicating the efficacy of adjuvant and palliative chemotherapy. Elevated levels of thymidine kinase must always be interpreted together with a detailed knowledge of the patients condition because nonspecific elevations of serum levels (inflammatory and autoimmune diseases) must be excluded.

Clinical Relevance of the Expression of mRNA of MMP-7, MMP-9, TIMP-1, TIMP-2 and CEA Tissue Samples from Colorectal Liver Metastases

Background: Nowadays we know that survival rates do not differ between repeated and single liver resections for colorectal liver metastases (CLM). To be able to determine patients prone to early recurrence, the use of different markers with a better prognostic value than the routinely employed tumor markers is required. Aim of Study: The aim of our study was to assess mRNA expression of MMP-7, MMP-9, TIMP-1, TIMP-2 and CEA in tissue samples from CLM and their relationship to disease-free interval (DFI) and overall survival (OS). Patients and Methods: The liver tumor biopsies were obtained from 40 patients suffering from CLM treated with radical surgery. mRNA expression levels of CEA, MMPs and TIMPs and a housekeeping gene (GAPDH) were quantified using RT-PCR. Results: The increased expression of CEA, MMP-9 and TIMP-1 in CLM was associated with a short DFI and a high tendency to early CLM recurrence. Statistical analysis confirmed CEA, MMP-9 and TIMP-1 expression as prognostic factors of survival. Conclusion: This study demonstrated the importance of CEA, MMP-9 and TIMP-1 in the prognostication of DFI and OS.

May CTC technologies promote better cancer management

In the case of cancer, death is usually not due to the primary tumor itself but due to dissemination. Analysis of the circulating tumor cells (CTCs), i.e., cells responsible for a formation of metastases, should provide information useful for the management of cancer patients, fulfilling the objectives of predictive, preventive, and personalized medicine (PPPM). Despite promising results, the decisions on stage of disease and how to guide the adjuvant treatment still do not include results of CTC assessment. We want to describe two major reasons why the recent diagnostic value of CTC analysis is not sufficient for clinical use. The first reason arises from the biological nature of the tumor itself and the second reason is associated with an interdisciplinary status of CTC diagnostics in the sense that it is neither a theme purely for pathologists nor for haemato-oncologists nor clinical biochemists. We anticipate that there are at least three areas where CTCs can be useful for clinical practice. The first is monitoring of treatment efficacy of cancer patients. The second is a molecular characterization of captured CTCs for targeted treatment, and the third is a cultivation of captured CTCs for drug sensitivity testing. All of these approaches allow researchers recognize and respond to changes of phenotype of cancer cells during disease progression and introduce PPPM into clinical practice.

Differential Acute Postprandial Effects of Processed Meat and Isocaloric Vegan Meals on the Gastrointestinal Hormone Response in Subjects Suffering from Type 2 Diabetes and Healthy Controls: A Randomized Crossover Study

Background The intake of meat, particularly processed meat, is a dietary risk factor for diabetes. Meat intake impairs insulin sensitivity and leads to increased oxidative stress. However, its effect on postprandial gastrointestinal hormone (GIH) secretion is unclear. We aimed to investigate the acute effects of two standardized isocaloric meals: a processed hamburger meat meal rich in protein and saturated fat (M-meal) and a vegan meal rich in carbohydrates (V-meal). We hypothesized that the meat meal would lead to abnormal postprandial increases in plasma lipids and oxidative stress markers and impaired GIH responses. Methods In a randomized crossover study, 50 patients suffering from type 2 diabetes (T2D) and 50 healthy subjects underwent two 3-h meal tolerance tests. For statistical analyses, repeated-measures ANOVA was performed. Results The M-meal resulted in a higher postprandial increase in lipids in both groups (p<0.001) and persistent postprandial hyperinsulinemia in patients with diabetes (p<0.001). The plasma glucose levels were significantly higher after the V-meal only at the peak level. The plasma concentrations of glucose-dependent insulinotropic peptide (GIP), peptide tyrosine-tyrosine (PYY) and pancreatic polypeptide (PP) were higher (p<0.05, p<0.001, p<0.001, respectively) and the ghrelin concentration was lower (p<0.001) after the M-meal in healthy subjects. In contrast, the concentrations of GIP, PYY and PP were significantly lower after the M-meal in T2D patients (p<0.001). Compared with the V-meal, the M-meal was associated with a larger increase in lipoperoxidation in T2D patients (p<0.05). Conclusion/Interpretation Our results suggest that the diet composition and the energy content, rather than the carbohydrate count, should be important considerations for dietary management and demonstrate that processed meat consumption is accompanied by impaired GIH responses and increased oxidative stress marker levels in diabetic patients. Trial Registration ClinicalTrials.gov NCT01572402

The Measurement of Intraocular Biomarkers in Various Stages of Proliferative Diabetic Retinopathy Using Multiplex xMAP Technology

Purpose. To determine the intraocular levels of growth factors and cytokines in patients with various degrees of severity of proliferative diabetic retinopathy (PDR) using multiplex xMAP technology. Methods. A prospective cohort study of 61 eyes from 56 patients who were divided into 3 groups based on the severity of PDR. Patients in group number 1 are those who presented PDR with no need of repeated surgical intervention; patients in group number 2 had repeated vitreous bleeding; and patients in group number 3 had refractory neovascular glaucoma. The concentrations of proangiogenic, antiangiogenic, inflammatory, and neurotrophic factors were measured in intraocular fluid. The results were also compared with levels of factors measured in 50 eyes from 50 patients prior to senile cataract surgery (control group). Results. Patients with refractory neovascular glaucoma (the highest clinical severity group) had higher levels of interleukin 6 (IL-6) (median1 37.19; median3 384.74; P = .00096), transforming growth factor beta 1 (TGFβ-1) (median1 49.00; median3 414.40; P = .0017), and vascular endothelial growth factor (VEGF) (median1 211.62; median3 352.82; P = .0454) compared with other PDR patients. Conclusions. Results of our study imply that levels of IL-6, TGFβ-1, and VEGF correlate with the severity of PDR.

Sperm antibodies, intra-acrosomal sperm proteins, and cytokines in semen in men from infertile couples.

Problem  The aim of this study was to investigate seminal sperm‐agglutinating antibodies, intra‐acrosomal proteins, sperm head abnormalities, and cytokines (IL‐1β, IL‐2, IL‐4, IL‐5, IL‐6, IL‐8, IL‐10, IL‐12p70 TNF‐α, and IFN‐γ) in men from infertile couples.

Current status of biomarker research in neurology

Neurology is one of the typical disciplines where personalized medicine has been recently becoming an important part of clinical practice. In this article, the brief overview and a number of examples of the use of biomarkers and personalized medicine in neurology are described. The various issues in neurology are described in relation to the personalized medicine and diagnostic, prognostic as well as predictive blood and cerebrospinal fluid biomarkers. Such neurological domains discussed in this work are neuro-oncology and primary brain tumors glioblastoma and oligodendroglioma, cerebrovascular diseases focusing on stroke, neurodegenerative disorders especially Alzheimer’s and Parkinson’s diseases and demyelinating diseases such as multiple sclerosis. Actual state of the art and future perspectives in diagnostics and personalized treatment in diverse domains of neurology are given.

ORIGINAL ARTICLE: Sperm Antibodies, Intra-Acrosomal Sperm Proteins, and Cytokines in Semen in Men from Infertile Couples

Problem  The aim of this study was to investigate seminal sperm‐agglutinating antibodies, intra‐acrosomal proteins, sperm head abnormalities, and cytokines (IL‐1β, IL‐2, IL‐4, IL‐5, IL‐6, IL‐8, IL‐10, IL‐12p70 TNF‐α, and IFN‐γ) in men from infertile couples.