Relationship between the Expression of Matrix Metalloproteinases and Their Tissue Inhibitors in Patients with Brain Tumors.

Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) play critical roles in regulating processes associated with malignant behavior. These endopeptidases selectively degrade components of the extracellular matrix (ECM), growth factors, and their receptors, contributing to cancer cell invasiveness and migratory characteristics by disrupting the basal membrane. However, the expression profile and role of various matrix metalloproteinases remain unclear, and only a few studies have focused on differences between diagnoses of brain tumors. Using quantitative real-time PCR analysis, we identified the expression pattern of ECM modulators (n = 10) in biopsies from glioblastoma (GBM; n = 20), astrocytoma (AST; n = 9), and meningioma (MNG; n = 19) patients. We found eight deregulated genes in the glioblastoma group compared to the benign meningioma group, with only MMP9 (FC = 2.55; p = 0.09) and TIMP4 (7.28; p < 0.0001) upregulated in an aggressive form. The most substantial positive change in fold regulation for all tumors was detected in matrix metalloproteinase 2 (MNG = 30.9, AST = 4.28, and GBM = 4.12). Notably, we observed an influence of TIMP1, demonstrating a positive correlation with MMP8, MMP9, and MMP10 in tumor samples. Subsequently, we examined the protein levels of the investigated MMPs (n = 7) and TIMPs (n = 3) via immunodetection. We confirmed elevated levels of MMPs and TIMPs in GBM patients compared to meningiomas and astrocytomas. Even when correlating glioblastomas versus astrocytomas, we showed a significantly increased level of MMP1, MMP3, MMP13, and TIMP1. The identified metalloproteases may play a key role in the process of gliomagenesis and may represent potential targets for personalized therapy. However, as we have not confirmed the relationship between mRNA expression and protein levels in individual samples, it is therefore natural that the regulation of metalloproteases will be subject to several factors.

Incidence and severity of dysphagia after anterior cervical discectomy and fusion with zero-profile spacer: prospective study with 3-years follow-up.

INTRODUCTION: Dysphagia after anterior cervical discectomy and fusion (ACDF) is a regular complication. The aim of this study was to identify risk factors for incidence and severity of dysphagia after ACDF with zero-profile spacer. METHODS: Incidence and severity of dysphagia was evaluated preoperatively and for time of three years after ACDF (regular outpatient check-ups) ‒ prospective study with 3-years follow-up. Severity of dysphagia was assessed subjectively using Bazaz‒Yoo dysphagia score. Influence of selected factors on the incidence and severity of postoperative dysphagia was evaluated. Following statistical methods were used: Fisher's exact test, unpaired Student's t-test, one-way ANOVA and Spearman's correlation coefficient. Level of significance was defined as p ˂ 0.05. Correlations between paired parameters were evaluated according to Spearman's correlation. RESULTS: Our study included 133 patients who underwent one-, two- or three-level ACDF with zero-profile spacer in years 2013‒2018. Myelopathy and GERD had significant impact on incidence and severity of pre-existing dysphagia. Risk factors for incidence of dysphagia after ACDF were number of treated segments, myelopathy, pre-existing dysphagia and surgery of C4/5 segment. Age of patients, duration of surgery and pre-existing dysphagia correlated positively very weakly to weakly with severity of dysphagia after ACDF. Number of treated segments, myelopathy, GERD and surgery of the C4/5 segment were risk factors for greater severity of postoperative dysphagia. CONCLUSION: Risk factors for incidence and severity of pre-existing dysphagia were myelopathy and GERD. Risk factors for dysphagia incidence after ACDF were number of treated segments, pre-existing dysphagia, myelopathy and surgery of C4/5 segment (Tab. 6, Fig. 1, Ref. 30).

Non-acute subdural hematoma: estimation of recurrence using CT-volumetric measurements.

OBJECTIVES: To identify risk factors for unilateral non-acute subdural hematomas NASH recurrence, as well as to perform volumetric quantitative analysis of hematoma, postoperative pneumocephalus and extent of hematoma evacuation. BACKGROUND: Recurrence of NASH increases morbidity and mortality and has negative socio-economic consequences. Its accurate prediction could improve patient specific care. METHODS: Records of 102 patients after unilateral NASH evacuation during the period from 2014 to 2020 with a 4-month follow-up were evaluated. Impacts of preoperative clinical signs and factors on the incidence of NASH recurrence were evaluated, namely those of age, gender, timing of surgery, hematoma side, surgical technique (number of burr holes, trepanation versus craniotomy), duration of drainage, antithrombotic agents, morphological type of hematoma, preoperative hematoma volume (PHV), post-evacuation hematoma cavity volume (PHCV), pneumocephalus volume (PCV) and extent of hematoma evacuation (EHE) on the incidence of NASH recurrence were evaluated. RESULTS: An overall recurrence rate of 13.7 % was observed. Preoperative hematoma volume, postoperative hematoma cavity volume and postoperative pneumocephalus volume had a significant impact on incidence of recurrence. CONCLUSIONS: Pre- and postoperative volumetric evaluations, of patients with NASH, particularly the measurements of preoperative hematoma volume and postoperative volume of hematoma cavity and pneumocephalus have a potential to improve the prediction of clinically significant recurrence (Tab. 6, Fig. 3, Ref. 51). Text in PDF www.elis.sk Keywords: subdural hematoma, recurrence, pneumocephalus, risk factors.

Metabolomic profiling of blood plasma in patients with primary brain tumours: Basal plasma metabolites correlated with tumour grade and plasma biomarker analysis predicts feasibility of the successful statistical discrimination from healthy subjects - a preliminary study.

The brain tumours represent a complex tissue that has its own characteristic metabolic features and is interfaced with the whole organism. We investigated changes in basal blood plasma metabolites in the presence of primary brain tumour, their correlation with tumour grade, as well as the feasibility of statistical discrimination based on plasma metabolites. Together 60 plasma samples from patients with clinically defined glioblastoma, meningioma, oligodendrioglioma, astrocytoma, and non-specific glial tumour and plasma samples from 28 healthy volunteers without any cancer history were measured by NMR spectroscopy. In blood plasma of primary brain tumour patients, we found significantly increased levels of glycolytic metabolites glucose and pyruvate, and significantly decreased level of glutamine and also metabolites participating in tricarboxylic acid (TCA) cycle, citrate and succinate, when compared with controls. Further, plasma metabolites levels: tyrosine, phenylalanine, glucose, creatine and creatinine correlated significantly with tumour grade. In general, observed changes are parallel to the biochemistry expected for tumourous tissue and metabolic changes in plasma seem to follow the similar rules in all primary brain tumours, with very subtle variations among tumour types. Only two plasma metabolites tyrosine and phenylalanine were increased exclusively in blood plasma of patients with glioblastoma. Based on metabolite levels, an excellent discrimination between plasma from patient's tumours and controls was attainable. The metabolites creatine, pyruvate, glucose, formate, creatinine and citrate were of the highest discriminatory power.

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.

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.

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.

Benign fibroepithelial polyp of the ureter.

Benign tumors of the ureter are rare and most often appear in the form of fibroepithelial polyps [1]. Fibroepithelial polyps represent from 2 to 6% of all benign tumors of the urinary tract [2]. The Authors report on two cases of fibroepithelial polyps of the ureter, which they treated between 1993-2009. One case was presented by acute urinary retention and gross hematuria. In the second case, hematuria and flank pain were observed. The first case was treated with open surgery and partial resection of the ureter, the second was treated endoscopically when the base of the polyp was well identified.

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

PURPOSE: To 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. METHODS: Forty 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. RESULTS: We 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. CONCLUSIONS: The 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.

Measurement of the blood flow velocity in the pericallosal artery of children with hydrocephalus by transcranial Doppler ultrasonography--preliminary results.

AIM: The goal of this study was to evaluate selected parameters of the Doppler curve of the pericallosal artery at children with hydrocephalus. METHODS: 12 patients with hydrocephalus were divided into two groups. Group 1 comprised children needing cerebrospinal fluid drainage, and group 2 comprised children without any indication for drainage or with an already inserted well-functioning drainage system. Dilatation of the cerebral ventricles was determined by transcranial ultrasonography. Following parameters of a blood flow of the pericallosal branch of the anterior cerebral artery: peak systolic blood flow velocity (PSFV), end-diastolic blood flow velocity (EDFV) and resistive index (RI) were observed by transcranial Doppler ultrasonography. Parameters of The Doppler curve were measured without pressure (baseline parameters) and during compression of the anterior fontanelle (pressure provocation test). RESULTS: Group 1: baseline parameters: PSFV 68.9 +/- 13.52 cm/s, EDFV 18.26 +/- 10.39 cm/s, RI 0.76 +/- 0.12; parameters during pressure provocation test: PSFV 66.92 +/- 19.75 cm/s, EDFV 10.88 +/- 11.18 cm/s, RI 0.86 +/- 0.14. Group 2: baseline parameters: PSFV 59.95 +/- 19.38 cm/s, EDFV 20.65 +/- 8 cm/s, RI 0.65 +/- 0.04; parameters during the pressure provocation test: PSFV 57.14 +/- 18.91 cm/s, EDFV 17.7 +/- 8.3 cm/s, RI 0.68 +/- 0.05. CONCLUSION: The results show increased baseline and postcompressive values of RI of pericallosal artery in infants with hydrocephalus before drainage procedure and normal values of RI at children without the need for cerebrospinal fluid drainage or with a well-functioning drainage system.