Romana Richterová

Most frequent molecular and immunohistochemical markers present in selected types of brain tumors

Tumors of brain tissue and meninges create a heterogeneous group with various biological behavior, therapy management and differing prognosis. Some of these do not require treatment, some can be cured by surgery and some are rapidly fatal despite treatment. Despite huge progress in tumor research, innovations in diagnostic tools and therapy, prognosis remains, in case of malignant tumor types, very serious. There has been an increased understanding of molecular abnormalities occurring in primary brain tumors. Genome-wide analyses of tumors have improved the knowledge in tumor biology. The aim of the research is to explain the oncogenesis features thus leading to the use of new therapeutic modalities in order to prolong survival rate of patients and at the same time providing satisfactory life quality. This article offers a short review of the basic genetic alterations present with some histological types of brain tumors.

Apoptosis-related gene expression in tumor tissue samples obtained from patients diagnosed with glioblastoma multiforme.

Tumors of the brain are very diverse in their biological behavior and are therefore considered a major issue in modern medicine. The heterogeneity of gliomas, their clinical presentation and their responses to treatment makes this type of tumor a challenging area of research. Glioblastoma multiforme (GBM) is the most common, and biologically the most aggressive, primary brain tumor in adults. The standard treatment for patients with newly diagnosed GBM consists of surgical resection, radiotherapy and chemotherapy. However, resistance to chemotherapy is a major obstacle to successful treatment. The aim of this study was to examine the changes occurring in the expression levels of apoptosis-associated genes in tumor tissue biopsy samples from 7 patients diagnosed with GBM and compare our results with a human astrocyte cell line (used as a reference) cultured under basic conditions. For molecular analysis, we used a commercial pre-designed microfluidic array to quantify the expression of 93 apoptosis-associated human genes. Significant changes in the expression levels of genes were observed in the tumor tissue samples obtained from patients with GBM. We determined significant changes in gene expression (n=32) in all apoptotic signaling pathways (BCl-2, TNF, Caspases, NF-κB, IAP and CARD), while the most pronounced deregulation (>5-fold) were observed in 46.9% events. The results of this study underline the importance of apoptosis in heterogenous tumor tissue. The identification of the apoptotic gene panel in tissue biopsies from patients with GBM may help improve the effectiveness of treatments for GBM in clinical practice and may broaden our understanding of brain tumor cell metabolism. Recognizing the changes in the expression of pro-apoptotic and anti-apoptotic genes may aid in the development of novel treatment strategies founded on a molecular basis.

The assessment of intracranial dynamics by transcranial Doppler sonography in perioperative period in paediatric hydrocephalus

PurposeTo evaluate Doppler parameters of anterior cerebral artery (ACA) and relationship to morphological parameters of cerebral ventricles and periventricular brain tissue in paediatric hydrocephalus before and after drainage procedure.MethodsForty newborns with hydrocephalus were evaluated before and after the drainage procedure. The morphological parameters of brain (ventricular index, width of ventricles, haemorrhagic lesions, asymmetric ventricular dilatation and dynamics of ventricles) were measured by transcranial ultrasonography. The haemodynamic parameters of ACA (peak systolic blood flow velocity, end-diastolic blood flow velocity and resistance index/RI/) were evaluated by Doppler ultrasonography. The correlation between morphological and haemodynamic parameters was analysed.ResultsWe found significant decrease of ventricular dilatation, which was accompanied with significant decrease of basal and compressive RI-ACA after drainage procedure. The correlation between basal RI-ACA, compressive RI-ACA and the dynamics of ventricular dilatation was not significant before and after drainage operation, as well. The significant correlation between preoperative basal RI-ACA, postoperative compressive RI-ACA and asymmetry of cerebral ventricles was confirmed. Statistical analysis showed significant correlation between basal RI-ACA, compressive RI-ACA and haemorrhagic lesions after drainage operation.ConclusionsThe results of our study showed the alteration of Doppler parameters of cerebral circulation in newborns with hydrocephalus before the drainage procedure. The successful drainage operation leads to the improvement of haemodynamic parameters of cerebral circulation. However, the statistical analysis showed the influence of some intracranial factors—the asymmetry of dilatation of lateral cerebral ventricles and periventricular haemorrhagic lesions on the Doppler parameters of cerebral circulation.

Proton MR spectroscopic imaging of human glioblastomas at 1.5 Tesla

In this study we evaluated clinical feasibility of proton magnetic resonance spectroscopy metabolite mapping (1H MRSI) by using 1.5 Tesla MR-scanner in 10 patients with high-grade glioblastoma. In vivo 1H MRSI performed with a relatively short scan time of 20 minutes enabled to obtain comprehensive information about metabolic changes in glioblastoma and adjacent tissues namely in the peritumoral edema, in the middle and solid part of the tumor, and in the normal-appearing brain tissue. Spectroscopically it was possible to identify initiation of neuronal cell death in the solid tumorous tissue via decreased N-acetyl-aspartate to creatine ratio (↓ tNAA/tCr) and expanding carcinogenesis reflected in elevated choline ratios (↑ tCho/tCr and tCho/tNAA). We showed also the central necrosis of glioblastoma accompanied by the tissue hypoxia, which were apparent as increased lactate and lipids ratios (↑ Lac/tCr and lip/Lac). Metabolic changes were noticeable also in the peritumoral area, showing the glioblastoma infiltration into the surrounding tissues. In intracranial tumors, 1H MRSI performed on 1.5 Tesla field strength was sufficient to provide information about the stage of carcinogenesis, tumor expansion or necrotization and thus it could be considered as a useful diagnostic tool in oncology.

Efficiency and Limitations of Decompressive Craniectomy in Patients after Traumatic Brain Injury – Preliminary Results

Abstract Introduction: Decompressive craniectomy (DC) has been recently proven effective tier II therapeutic procedure in the treatment of refractory posttraumatic intracranial hypertension. However, its full potential and effectivity is yet to be described and this surgery remains controversial. The goals of our study include analysis of efficiency of DC and description of risk factors associated with unfavourable outcome. Methods: 24 patients who underwent DC at the Clinic of Neurosurgery, JFM CU in Martin, during years 2015–2016 were prospectively observed. Selected demographic, clinical, and radiographic factors were analysed and compared with patient’s GOS (Glasgow Outcome Scale) at the time of their first ambulatory control (after 3.5 months in average). Results: We observed mortality of 29.17 %. Good outcome (GOS 4–5) was achieved by 29.17 % of the patients as well. Preoperative GCS ≤ 5 (p = 0.049), intraventricular bleeding (p = 0.0268), midline shift ≥ 15 mm (p = 0.0067), and the volume of intracranial lesion (R = −0.41, p = 0.046), especially its extracerebral component (R = −0.46, p = 0.02), were identified as statistically significant negative prognostic factors. Conclusion: DC is effective in the management of patients with traumatic brain injury. Good outcome is achieved by 29.17 % of the patients. Described negative prognostic factors (preoperative GCS ≤ 5, intraventricular bleeding, midline shift ≥ 15 mm, and increasing the volume of traumatic mass lesion) could help in targeting this surgery only to patients who are expected to benefit from it.

Genetic Alterations of Glioblastoma

The current research in oncology is focused on genetics and molecular oncology in order to obtain better understanding of the etiology of tumor disease. Detailed knowledge of oncogenesis mechanisms could lead to invention of effective therapeutic tools against cancer. Under healthy conditions, cell cycle is regulated by oncogenes and tumor suppressor genes, which should be in strict balance. Genesis of tumor is a consequence of the accumulation of genetic alterations, which help the cell to escape normal cellular regulatory mechanisms and destruction by immune system. Glioblastoma (GBM) is a highly malignant primary brain tumor occurring mostly in population of adults. Patients suffering from GBM have very poor prognosis. Despite development in radiology methods promising earlier diagnosis and development of clinical and radiation oncology with newer treatment regimes, the effect of therapy remains limited and prognosis of patients has not improved as expected. Target of GBM research are genes involved in response to oxidative stress and DNA damage, genes regulating cell cycle, genes determining immune response, growth factors, and others. Genetic alterations are studied in connection to their possible relationship to susceptibility of brain tissue for tumor formation, to sensitivity of brain tissue for various environmental etiology factors, to effect of anticancer treatment or resistance of tumor tissue to therapy, to overall survival, and progression-free interval.