1. Expression of LOC285758, a potential long non-coding biomarker, is methylation- dependent and correlates with glioma malignancy gradeAlenka Matjašič, Mara Popović, Boštjan Matos, Damjan Glavač, 2017, izvirni znanstveni članek Povzetek: Background. Identifying the early genetic drivers can help diagnose glioma tumours in their early stages, before becoming malignant. However, there is emerging evidence that disturbance of epigenetic mechanisms also con- tributes to cell's malignant transformation and cancer progression. Long non-coding RNAs are one of key epigenetic modulators of signalling pathways, since gene expression regulation is one of their canonical mechanisms. The aim of our study was to search new gliomagenesis-specific candidate lncRNAs involved in epigenetic regulation. Patients and methods. We used a microarray approach to detect expression profiles of epigenetically involved lncRNAs on a set of 12 glioma samples, and selected LOC285758 for further qPCR expression validation on 157 glioma samples of different subtypes. To establish if change in expression is a consequence of epigenetic alterations we determined methylation status of lncRNA's promoter using MS-HRM. Additionally, we used the MLPA analysis for de- termining the status of known glioma biomarkers and used them for association analyses. Results. In all glioma subtypes levels of LOC285758 were significantly higher in comparison to normal brain reference RNA, and expression was inversely associated with promoter methylation. Expression substantially differs between astrocytoma and oligodendroglioma, and is elevated in higher WHO grades, which also showed loss of methylation. Conclusions. Our study revealed that lncRNA LOC285758 changed expression in glioma is methylation-dependent and methylation correlates with WHO malignancy grade. Methylation is also distinctive between astrocytoma I-III and other glioma subtypes and may thus serve as an additional biomarker in glioma diagnosis.
Ključne besede: glioma, epigenetics, methylation
Objavljeno v DiRROS: 03.06.2024; Ogledov: 30; Prenosov: 26
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2. Long-term survival in glioblastoma : methyl guanine methyl transferase (MGMT) promoter methylation as independent favourable prognostic factorUroš Smrdel, Mara Popović, Matjaž Zwitter, Emanuela Boštjančič, Andrej Zupan, Viljem Kovač, Damjan Glavač, Drago Bokal, Janja Jerebic, 2016, izvirni znanstveni članek Povzetek: In spite of significant improvement after multi-modality treatment, prognosis of most patients with glioblastoma remains poor. Standard clinical prognostic factors (age, gender, extent of surgery and performance status) do not clearly predict long-term survival. The aim of this case-control study was to evaluate immuno-histochemical and genetic characteristics of the tumour as additional prognostic factors in glioblastoma. Long-term survivor group were 40 patients with glioblastoma with survival longer than 30 months. Control group were 40 patients with shorter survival and matched to the long-term survivor group according to the clinical prognostic factors. All patients underwent multimodality treatment with surgery, postoperative conformal radiotherapy and temozolomide during and after radiotherapy. Biopsy samples were tested for the methylation of MGMT promoter (with methylation specific polymerase chain reaction), IDH1 (with immunohistochemistry), IDH2, CDKN2A and CDKN2B (with multiplex ligation-dependent probe amplification), and 1p and 19q mutations (with fluorescent in situ hybridization). Methylation of MGMT promoter was found in 95% and in 36% in the long-term survivor and control groups, respectively (p < 0.001). IDH1 R132H mutated patients had a non-significant lower risk of dying from glioblastoma (p= 0.437), in comparison to patients without this mutation. Other mutations were rare, with no significant difference between the two groups. Molecular and genetic testing offers additional prognostic and predictive information for patients with glioblastoma. The most important finding of our analysis is that in the absence of MGMT promoter methylation, longterm survival is very rare. For patients without this mutation, alternative treatments should be explored.
Ključne besede: glioblastoma, long-term survival, methyl guanine methyl transferase, MGMT, prognostic factor
Objavljeno v DiRROS: 30.04.2024; Ogledov: 133; Prenosov: 117
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3. Glioblastoma patients in Slovenia from 1997 to 2008Uroš Smrdel, Viljem Kovač, Mara Popović, Matjaž Zwitter, 2014, izvirni znanstveni članek Povzetek: Glioblastoma is the most common primary brain tumour. It has a poor prognosis despite some advances in treatment that have been achieved over the last ten years. In Slovenia, 50 to 60 glioblastoma patients are diagnosed each year. In order to establish whether the current treatment options have any influence on the survival of the Slovenian glioblastoma patients, their data in the period from the beginning of the year 1997 to the end of the year 2008 have been analysed. Patients and methods. All patients treated at the Institute of Oncology Ljubljana from 1997 to 2008 were included in the retrospective study. Demographics, treatment details, and survival time after the diagnosis were collected and statistically analysed for the group as a whole and for subgroups. Results. From 1997 to 2008, 527 adult patients were diagnosed with glioblastoma and referred to the Institute of Oncology for further treatment. Their median age was 59 years (from 20 to 85) and all but one had the diagnosis confirmed by a pathologist. Gross total resection was reported by surgeons in 261 (49.5%) patients; good functional status (WHO 0 or 1) after surgery was observed in 336 (63.7%) patients, radiotherapy was performed in 422 (80.1%) patients, in 317 (75.1%) of them with radical intent, and 198 (62.5 %) of those received some form of systemic treatment (usually temozolomide). The median survival of all patients amounted to 9.7 months. There was no difference in median survival of all patients or of all treated patients before or after the chemo-radiotherapy era. However, the overall survival of patients treated with radical intent was significantly better (11.4 months; p < 0.05). A better survival was also noticed in radically treated patients who received additional temozolomide therapy (11.4 vs. 13.1 months; p = 0.014). The longer survival was associated with a younger age and a good performance status as well as with a more extensive tumour resection. In patients treated with radical intent, having a good performance status, and receiving radiotherapy and additional temozolomide therapy, the survival was significantly longer, based on multivariate analysis.
Ključne besede: glioblastoma, treatment, survival, surgery, radiotherapy, termozolomide
Objavljeno v DiRROS: 11.04.2024; Ogledov: 338; Prenosov: 383
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4. Genetic markers in oligodendroglial tumoursTomaž Velnar, Uroš Smrdel, Mara Popović, Gorazd Bunc, 2010, pregledni znanstveni članek Povzetek: Background. Oliogodendrogliomas are brain tumours composed of the cells resembling oligodendrocytes. They represent the third most common glial tumour, comprising 2.5% of all primary brain tumours and 5-20% of all gliomas. Conclusions. Oligodendroglial tumours with 1p and 19q loss demonstrate a better overall prognosis due to more indolent clinical behaviour and higher sensitivity to treatment. Additionally, 1p and 19q loss is a marker of clinical utility, helping to assess tumour sensitivity to chemotherapy and harbouring the potential for improving the diagnosis and survival of oligodendroglioma patients as well as future clinical practice.
Objavljeno v DiRROS: 15.03.2024; Ogledov: 142; Prenosov: 35
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7. Progresivna multifokalna levkoencefalopatija po rituksimabu pri bolniku z recidivnim limfomom plaščnih celic v popolni remisijiTanja Roš-Opaškar, Matej Horvat, Mara Popović, Barbara Jezeršek Novaković, 2012, izvirni znanstveni članek Povzetek: Progresivna multifokalna levkoencefalopatija (PML) je redko in običajno smrtno demielinizacijsko obolenje možganov, ki se razvije skoraj izključno pri bolnikih z imunsko pomanjkljivostjo in je posledica reaktivacije latentne okužbe s polioma virusom JC. V zadnjih letih so opisani tudi primeri PML po zdravljenju z rituksimabom. Predstavljamo naš prvi potrjeni primer PML pri 55-letnem HIV-negativnem bolniku z recidivnim limfomom plaščnih celic, pri katerem smo raka uspešno zdravili s kemoterapijo in rituksimabom ter z avtologno presaditvijo perifernih krvotvornih matičnih celic (PKMC). S primerom želimo opozoriti na pomembnost PML v diferencialni diagnozi pri bolnikih z napredujočo nevrološko simptomatiko in imunsko pomanjkljivostjo po zdravljenju limfoma z rituksimabom ter pomembnost zgodnjega prepoznavanja te bolezni z dokazom JC-virusne okužbe v likvorju ali v vzorcu stereotaktične biopsije možganov.
Objavljeno v DiRROS: 31.08.2018; Ogledov: 3347; Prenosov: 820
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