Purpose.To assess FGF-β, TGF-β, and COX2 expression and immunocompetent cells in the orbital tissue of patients with severe and mild Graves’ orbitopathy.Patients and Methods.Orbital tissue was taken from 27 patients with GO: (1) severe GO (n=18), the mean clinical activity score (CAS) being 8.5 (SD 2.5); and (2) mild GO (n=9), the mean CAS being 2.2 (SD 0.8), and from 10 individuals undergoing blepharoplasty. The expression of CD4+, CD8+, CD20+, and CD68 and FGF-β, TGF-β, and COX2 in the orbital tissue was evaluated by immunohistochemical methods.Results.We demonstrated predominant CD4+ T cells in severe GO. CD68 expression was observed in the fibrous connective area of mild GO and was robust in severe GO, while the prominent TGF-βexpression was seen in all GO. Increased FGF-βexpression was observed in the fibroblasts and adipocytes of severe GO. No expression of COX2 was found in patients with GO.Conclusions.Macrophages and CD4 T lymphocytes are both engaged in the active/severe and long stage of inflammation in the orbital tissue. FGF-βand TGF-βexpression may contribute to tissue remodeling, fibrosis, and perpetuation of inflammation in the orbital tissue of GO especially in severe GO.

Meningiomas constitute up to 13% of all intracranial tumors. The predictive factors for meningioma have not been unambiguously defined; however some limited data suggest that the expression of matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) may be associated with the presence of peritumoral brain edema (PTBE) and worse clinical outcome. The aim of this study was to analyze the expressions of MMP-9 and VEGF in a group of meningiomas of various grades and to study associations between these two markers and PTBE. The study included patients with supratentorial meningiomas. The patients were divided into low- (G1) and high-grade meningiomas (G2 and G3). PTBE was assessed on MRI. The expressions of VEGF and MMP-9 were determined immunohistochemically. The expression of MMP-9 was observed significantly more often in G3 meningiomas than in lower grade tumors. The presence of stage II or III PTBE was associated with a significant increase in MMP-9 expression. The expression of VEGF did not differ across the PTBE stages. Our findings point to a significant role of MMP-9 and VEGF in the pathogenesis of peritumoral brain edema in low- and high-grade meningiomas.

Meningiomas are common primary brain tumors. However, they are often complicated by significant peritumoral brain edema, which leads to surgery difficulties and prolonged hospitalization. The aim of this study was to evaluate the presence of mast cells and expression of hypoxia inducible factor-1 (HIF-1) in correlation with the grade of meningioma and presence of peritumoral brain edema. Immunohistochemistry was performed with specific antibodies against tryptase (mast cells) and HIF-1 in low grade meningiomas (estimated as G1) and high grade meningiomas (estimated as G2 or G3). Peritumoral brain edema observed in MRI was graded using Steinhoff classification. Tryptase expression was observed in 40.4 % low grade meningiomas and in 90 % high grade cases; HIF-1 in 55.7 % low grade and in 84 % high grade meningiomas. There was a statistically significant correlation between HIF-1 and tryptase expression in both groups (p = 0.003). Presence of peritumoral brain edema statistically correlated with tryptase (p = 0.001) and HIF-1 expression (p = 0.004). Mast cells as well as hypoxia are involved in meningioma progression, and may be associated with the formation of peritumoral brain edema leading to surgery complication and recovery. Therefore, they may be useful markers in predicting the clinical course of meningioma cases.

Background: The tissue-mechanics environment plays a crucial role in human brain physiological development and the pathogenesis of different diseases, especially cancer. Assessment of alterations in brain mechanical properties during cancer progression might provide important information about possible tissue abnormalities with clinical relevance. Methods: With atomic force microscopy (AFM), the stiffness of freshly removed human brain tumor tissue was determined on various regions of the sample and compared to the stiffness of healthy human brain tissue that was removed during neurosurgery to gain access to tumor mass. An advantage of indentation measurement using AFM is the small volume of tissue required and high resolution at the single-cell level. Results: Our results showed great heterogeneity of stiffness within metastatic cancer or primary high-grade gliomas compared to healthy tissue. That effect was not clearly visible in lower-grade tumors like meningioma. Conclusion: Collected data indicate that AFM might serve as a diagnostic tool in the assessment of human brain tissue stiffness in the process of recognizing tumors.

(1) Background: The novel hybrid of positron emission tomography/magnetic resonance (PET/MR) examination has been introduced to clinical practice. The aim of our study was to evaluate PET/MR usefulness in preoperative staging of head and neck cancer (HNC) patients (pts); (2) Methods: Thirty eight pts underwent both computed tomography (CT) and PET/MR examination, of whom 21 pts underwent surgical treatment as first-line therapy and were further included in the present study. Postsurgical tissue material was subjected to routine histopathological (HP) examination with additional evaluation of p16, human papillomavirus (HPV), Epstein-Barr virus (EBV) and Ki67 status. Agreement of clinical and pathological T staging, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) of CT and PET/MR in metastatic lymph nodes detection were defined. The verification of dependences between standardized uptake value (SUV value), tumor geometrical parameters, number of metastatic lymph nodes in PET/MR and CT, biochemical parameters, Ki67 index, p16, HPV and EBV status was made with statistical analysis of obtained results; (3) Results: PET/MR is characterized by better agreement in T staging, higher specificity, sensitivity, PPV and NPV of lymph nodes evaluation than CT imaging. Significant correlations were observed between SUVmax and maximal tumor diameter from PET/MR, between SUVmean and CT tumor volume, PET/MR tumor volume, maximal tumor diameter assessed in PET/MR. Other correlations were weak and insignificant; (4) Conclusions: Hybrid PET/MR imaging is useful in preoperative staging of HNC. Further studies are needed.

Identification of the NSCLC subtype at an early stage is still quite sophisticated. Metabolomics analysis of tissue and plasma of NSCLC patients may indicate new, and yet unknown, metabolic pathways active in the NSCLC. Our research characterized the metabolomics profile of tissue and plasma of patients with early and advanced NSCLC stage. Samples were subjected to thorough metabolomics analyses using liquid chromatography-mass spectrometry (LC-MS) technique. Tissue and/or plasma samples from 137 NSCLC patients were analyzed. Based on the early stage tissue analysis, more than 200 metabolites differentiating adenocarcinoma (ADC) and squamous cell lung carcinoma (SCC) subtypes as well as normal tissue, were identified. Most of the identified metabolites were amino acids, fatty acids, carnitines, lysoglycerophospholipids, sphingomyelins, plasmalogens and glycerophospholipids. Moreover, metabolites related to N-acyl ethanolamine (NAE) biosynthesis, namely glycerophospho (N-acyl) ethanolamines (GP-NAE), which discriminated early-stage SCC from ADC, have also been identified. On the other hand, the analysis of plasma of chronic obstructive pulmonary disease (COPD) and NSCLC patients allowed exclusion of the metabolites related to the inflammatory state in lungs and the identification of compounds (lysoglycerophospholipids, glycerophospholipids and sphingomyelins) truly characteristic to cancer. Our results, among already known, showed novel, thus far not described, metabolites discriminating NSCLC subtypes, especially in the early stage of cancer. Moreover, the presented results also indicated the activity of new metabolic pathways in NSCLC. Further investigations on the role of NAE biosynthesis pathways in the early stage of NSCLC may reveal new prognostic and diagnostic targets.