Browsing by Subject "glioma"

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  • Korja, Miikka; Raj, Rahul; Seppä, Karri; Luostarinen, Tapio; Malila, Nea; Seppälä, Matti; Mäenpää, Hanna; Pitkäniemi, Janne (2019)
    We assessed population-level changes in glioblastoma survival between 2000 and 2013 in Finland, with focus on elderly patients (> 70 y) in order to assess if changes in treatment of glioblastoma are reflected also in population-based survival rates. We identified all patients (age 18 y) from the Finnish Cancer Registry (FCR) with a histopathological diagnosis of primary glioblastoma in 20002013. Patients were followed up until December 2015. The accuracy of register-based search of glioblastoma patients was internally validated. We report age-standardized relative survival ratios and relative excess risks (RERs) of death in 20002006 (pre-period) and 20072013 (post-period). We identified 2045 glioblastoma patients from the FCR. The accuracy of the FCR-based search was 97%. Median age was 63.3 years, and 42% were women. Incidence increased on average by 1.6% (P = 0.004) and median age by 0.4 years per calendar year. Between the pre- and post-periods, the proportion of patients > 70 years increased from 24% to 27%. In > 70-year-old patients, the median survival time increased from 3.6 months in 20002006 to 4.5 months in 20072013 (RER 0.82, 95% CI: 0.680.98). In 70-year-old patients, the median survival time increased from 9.3 months in 20002006 to 11.7 months in 20072013 (RER 0.74, 95% CI: 0.670.82). Despite the increased proportion of elderly glioblastoma patients, population-level survival of glioblastoma patients has improved since the year 2000. However, increasing incidence, increasing age of patients, and poor survival in elderly are alarming, and future studies should perhaps focus more on elderly.
  • Peltonen, Sirkku; Kallionpaa, Roope A.; Rantanen, Matti; Uusitalo, Elina; Lähteenmäki, Päivi M.; Pöyhönen, Minna; Pitkäniemi, Janne; Peltonen, Juha (2019)
    Neurofibromatosis type 1 (NF1) is a cancer predisposition syndrome with an incidence of 1:2,000. Patients with NF1 have an increased cancer risk and mortality, but there are no population-based cohort studies specifically investigating the risk of childhood malignancies. We used the Finnish NF1 cohort to analyze the incidence, risk and prognosis of malignancies in NF1 patients
  • Cheray, Mathilde; Stratoulias, Vassilis; Joseph, Bertrand; Grabert, Kathleen (2019)
    Microglia, the immune cells of the brain, play a major role in the maintenance of brain homeostasis and constantly screen the brain environment to detect any infection or damage. Once activated by a stimulus, microglial cells initiate an immune response followed by the resolution of brain inflammation. A failure or deviation in the housekeeping function of these guardian cells can lead to multiple diseases, including brain cancer and neurodegenerative diseases such as Alzheimer's disease (AD). A small number of studies have investigated the causal relation of both diseases, thereby revealing an inverse relationship where cancer patients have a reduced risk to develop AD and vice versa. In this review, we aim to shed light on the role of microglia in the fate to develop specifically glioma as one type of cancer or AD. We will examine the common and/or opposing genetic predisposition as well as associated pathways of these diseases to unravel a possible involvement of microglia in the occurrence of either disease. Lastly, a set of guidelines will be proposed for future research and diagnostics to clarify and improve the knowledge on the role of microglia in the decision toward one pathology or another.
  • Le Joncour, Vadim; Filppu, Pauliina; Hyvönen, Maija; Holopainen, Minna; Turunen, S. Pauliina; Sihto, Harri; Burghardt, Isabel; Joensuu, Heikki; Tynninen, Olli; Jääskeläinen, Juha; Weller, Michael; Lehti, Kaisa; Käkelä, Reijo; Laakkonen, Pirjo (2019)
    The current clinical care of glioblastomas leaves behind invasive, radio- and chemo-resistant cells. We recently identified mammary-derived growth inhibitor (MDGI/FABP3) as a biomarker for invasive gliomas. Here, we demonstrate a novel function for MDGI in the maintenance of lysosomal membrane integrity, thus rendering invasive glioma cells unexpectedly vulnerable to lysosomal membrane destabilization. MDGI silencing impaired trafficking of polyunsaturated fatty acids into cells resulting in significant alterations in the lipid composition of lysosomal membranes, and subsequent death of the patient-derived glioma cells via lysosomal membrane permeabilization (LMP). In a preclinical model, treatment of glioma-bearing mice with an antihistaminergic LMP-inducing drug efficiently eradicated invasive glioma cells and secondary tumours within the brain. This unexpected fragility of the aggressive infiltrating cells to LMP provides new opportunities for clinical interventions, such as re-positioning of an established antihistamine drug, to eradicate the inoperable, invasive, and chemo-resistant glioma cells from sustaining disease progression and recurrence.