Background: It has recently been reported by several sources that original (i.e., present in vivo) glioma cell phenotypes or genotypes cannot be maintained in vitro. For example, glioblastoma cell lines presenting EGFR amplification cannot be established. Methods and results: IDH1 sequencing and loss of heterozygosity analysis was performed for 15 surgery samples of astrocytoma and early and late passages of cells derived from those and for 11 archival samples. We were not able to culture tumour cells presenting IDH1 mutations originating from currently proceeded 10 tumours; the same results were observed in 7 samples of archival material. Conclusion: The IDH1 mutation is expected to be almost mutually exclusive with EGFR amplification, so glioma cells with IDH1 mutations seem to represent a new group of tumour cells, which cannot be readily analysed in vitro because of their elimination. The reasons for this intriguing phenomenon should be investigated since its understanding can help to define a new therapeutic approach based on simulating in vivo conditions, responsible for tumour cells elimination in vitro. Moreover, a new model for culturing glioma cells in vitro should be designed since the current one does not provide conditions corresponding to in vivo growth.

Glutamine (Gln) is a growth determinant in neoplastic tissues. We analysed by RT-PCR the expression of mRNAs coding for the human variants of Gln transporters: ASCT2 (system ASC), SNAT1 [ATA1] (system A), SNAT3 [SN1] and SNAT5 [SN2] (system N), in samples of human malignant gliomas WHO grades III/IV (anaplastic astrocytoma and glioblastoma), glioma-derived cell cultures, brain metastases from peripheral organs, and control brain tissue. (Transporters designated according to the nomenclature recently proposed by Mckenzie and Ericksson [1]. Original designations in square brackets.) SNAT3 mRNA showed a 3–5 times stronger expression in gliomas than in metastases or control tissue, and was virtually absent from glioma cultures. Native glioblastoma immunostained positively with anti-SNAT3 antibody. The expression of ASCT2 mRNA, but not SNAT5 or SNAT1 mRNAs, was increased in all neoplastic tissues studied. Hence, increased expression of SNAT3 is a marker of primary malignant gliomas in situ.

The rupture of saccular intracranial aneurysms (IA) is the commonest cause of non-traumatic subarachnoid hemorrhage (SAH)—the most serious form of stroke with a high mortality rate. Aneurysm walls are usually characterized by an active inflammatory response, and NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) has been identified as the main transcription factor regulating the induction of inflammation-related genes in IA lesions. This transcription factor has also been related to IA rupture and resulting SAH. We and others have shown that autophagy interacts with inflammation in many diseases, but there is no information of such interplay in IA. Moreover, NF-κB, which is a pivotal factor controlling inflammation, is regulated by autophagy-related proteins, and autophagy is regulated by NF-κB signaling. It was also shown that autophagy mediates the normal functioning of vessels, so its disturbance can be associated with vessel-related disorders. Early brain injury, delayed brain injury, and associated cerebral vasospasm are among the most serious consequences of IA rupture and are associated with impaired function of the autophagy–lysosomal system. Further studies on the role of the interplay between autophagy and NF-κB-mediated inflammation in IA can help to better understand IA pathogenesis and to identify IA patients with an increased SAH risk.

Tumour necrosis factor‐related apoptosis‐inducing ligand (TRAIL) has been reported to induce apoptosis in various tumour cell lines and, recently, also in normal cells. TRAIL interacts with four receptors: two signalling receptors (TRAIL‐R1 and TRAIL‐R2) and two decoy receptors (TRAIL‐R3 and TRAIL‐R4). We have shown that both signalling receptors are present on the surface of oligodendrocytes isolated from adult human brain (ahOL), whereas the decoy receptors are expressed at a low level on ahOL. TRAIL induces ahOL apoptosis—as characterized by Annexin V staining prior to propidium iodide cell uptake—under conditions of protein synthesis inhibition. However, pre‐treatment of ahOL with interferon γ (IFNγ) evoked susceptibility to TRAIL‐induced death, which did not require inhibition of protein synthesis. A blocking experiment with monoclonal antibodies directed against TRAIL‐R1 and TRAIL‐R2 revealed that TRAIL‐R1 is mainly involved in TRAIL‐induced apoptosis of ahOL. In contrast to ahOL, microglial cells were completely resistant to cell death induced by TRAIL. Microglial cells had high surface expression of the decoy receptor TRAIL‐R3, suggesting that resistance of these glial cells to TRAIL‐induced death depends on the presence of the protective effect of TRAIL‐R3. Stimulation of microglia with TRAIL increased further expression of TRAIL‐R3, but it had no effect on the expression of TRAIL receptors by ahOL. This result may implicate TRAIL as an effector‐immune molecule in selective ahOL demise in inflammatory/demyelinating conditions.

Although features of variable differentiation in glioblastoma cell cultures have been reported, a comparative analysis of differentiation properties of normal neural GFAP positive progenitors, and those shown by glioblastoma cells, has not been performed.

Von Hippel-Lindau (VHL) disease is a rare autosomal dominant disorder characterised by a predisposition to haemangioblastomas of the central nervous system (cHAB) and retina (rHAB), renal cell carcinomas (RCC), phaeochromocytomas and paragangliomas, endolymphatic sac tumours (ELST), pancreatic neuroendocrine tumours (PNET), papillary cystadenomas of epididymis, and adnexal papillary tumours of probable mesonephric origin (APMO). Renal, pancreatic, epididymal, and broad ligament cysts also occur frequently.1 It is caused by germline mutations in the VHL tumour suppressor gene on chromosome 3p25-26.2,3 VHL disease occurs with an estimated incidence of 1:36 000 live births and shows variable expression and age dependent penetrance that is almost complete by the age of 65.4 Median actuarial life expectancy of VHL subjects is reduced to 49 years, renal cell carcinoma5 or CNS haemangioblastoma6 being the most common cause of death. At present, early diagnosis and treatment of VHL associated tumours result in improved prognosis for VHL subjects.7 The disease can be diagnosed on the basis of clinical criteria in the presence of a single haemangioblastoma, phaeochromocytoma, multiple pancreatic cysts, or renal cell carcinoma in a member of a VHL family. For clinical diagnosis of isolated cases of VHL, at least two haemangioblastomas or a single haemangioblastoma in association with a visceral manifestation are required.8 In early studies, using standard Southern analysis and sequencing of the VHL coding region, disease causing mutations were detected in 38-80% of families fulfilling clinical VHL criteria.1 More recently, the development of quantitative Southern analysis (QSA) to detect partial and complete deletions has improved VHL mutation detection. QSA analysis in conjunction with direct sequencing of the coding region showed germline mutations in 100% of 93 families with definite VHL.9 However, the results implying that all cases fulfilling clinical VHL criteria are related to mutations …