We describe the landscape of somatic genomic alterations based on multidimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors, including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer.

The somatic genomic landscape of glioblastoma

正しい方法がわかる臨床基本手技 : from the New England journal of medicine

European Organization for Research and Treatment of Cancer

Moyamoya disease is an uncommon cerebrovascular disease that is characterised by progressive stenosis of the terminal portion of the internal carotid artery and its main branches. The disease is associated with the development of dilated, fragile collateral vessels at the base of the brain, which are termed moyamoya vessels. The incidence of moyamoya disease is high in east Asia, and familial forms account for about 15% of patients with this disease. Moyamoya disease has several unique clinical features, which include two peaks of age distribution at 5 years and at about 40 years. Most paediatric patients have ischaemic attacks, whereas adult patients can have ischaemic attacks, intracranial bleeding, or both. Extracranial-intracranial arterial bypass, including anastomosis of the superficial temporal artery to the middle cerebral artery and indirect bypass, can help prevent further ischaemic attacks, although the beneficial effect on haemorrhagic stroke is still not clear. In this Review, we summarise the epidemiology, aetiology, clinical features, diagnosis, surgical treatment, and outcomes of moyamoya disease. Recent updates and future perspectives for moyamoya disease will also be discussed.

https://www.thelancet.com/pdfs/journals/laneur/PIIS1474-4422(08)70240-0.pdf

Moyamoya disease: current concepts and future perspectives

Temozolomide (TMZ) is an oral alkylating agent used to treat glioblastoma multiforme (GBM) and astrocytomas. However, at least 50% of TMZ treated patients do not respond to TMZ. This is due primarily to the over-expression of O6-methylguanine methyltransferase (MGMT) and/or lack of a DNA repair pathway in GBM cells. Multiple GBM cell lines are known to contain TMZ resistant cells and several acquired TMZ resistant GBM cell lines have been developed for use in experiments designed to define the mechanism of TMZ resistance and the testing of potential therapeutics. However, the characteristics of intrinsic and adaptive TMZ resistant GBM cells have not been systemically compared. This article reviews the characteristics and mechanisms of TMZ resistance in natural and adapted TMZ resistant GBM cell lines. It also summarizes potential treatment options for TMZ resistant GBMs.

Temozolomide resistance in glioblastoma multiforme

The authors describe a series of 15 intracranial germ cell tumors (IGCTs) excluding mature teratomas; 3 cases in children younger than 3 years of age who were treated at 3 different international institutions over the course of 20 years, and 12 from a PubMed search. These tumors, with possible in utero origins, often occur in atypical locations. The clinical behavior differed significantly from these tumors' counterparts in older children. In this young age group germinoma is highly aggressive, whereas nongerminomatous germ cell tumors may be cured without radiotherapy. Ongoing genomic studies reveal insights to attain an understanding of the biology of these tumors. New treatment strategies are needed to improve outcomes for IGCTs in this age group, particularly for germinomas.

Atypical location and clinical behavior of a subset of intracranial germ cell tumors in children younger than 3 years of age

Clinical images: myositis ossificans of the upper extremity.

This study aimed to describe the survival trajectory of dental restorations placed in an outpatient population of geriatric and adult special needs patients over a 15-year span, with particular interest in longevity of subsequent restorations in teeth that received multiple restorations over time. Dental restorations of different types and sizes in patients age ≥65 years treated between 2000-14 at the University of Iowa, College of Dentistry were followed until they incurred an event (i.e., restoration replacement, extraction of the tooth, or endodontic treatment of the tooth). Survival analysis and extended Cox regression models were used to generate hazards ratios for selected predictor variables. A total of 9184 restorations were followed in 1551 unique patients. During the follow-up period, 28.7% of these restorations incurred an event; and overall the restorations had a median lifespan of 6.25 years. In multivariable regression models, after controlling for gender and age, composite restorations and greater number of restoration surfaces were associated with higher risks of failure; and the initial restoration recorded in the database for each subject tended to have lower risk of failure than restorations placed later that included any of those same surfaces. This information potentially could be helpful to elderly patients considering various restorative treatment options during the dental treatment planning and informed consent process.

https://www.biorxiv.org/content/biorxiv/early/2018/04/03/202069.full.pdf

Dental restoration longevity among geriatric and adult special needs patients

Exth-28. 5-aminolevulinic acid-based photodynamic therapy of glioblastoma tumorsphere and acquired resistance by tumor mesenchymal stem-like cells


 
 
 In glioblastoma (GBM) patients, controlling the microenvironment around the tumor using various treatment modalities, including surgical intervention, is essential in determining the outcome of treatment. This study was conducted to elucidate whether recurrence patterns differ according to the extent of resection (EOR) and whether this difference affects prognosis.
 
 
 
 This single-center study included 358 eligible patients with histologically confirmed isocitrate dehydrogenase (IDH)-wild-type GBM from November 1, 2005, to December 31, 2018. Patients were assigned to one of three separate groups according to EOR: supratotal resection (SupTR), gross-total resection (GTR), and subtotal resection (STR) groups. The patterns of recurrence were classified as local, marginal, and distant based on the range of radiation. The relationship between EOR and recurrence pattern was statistically analyzed.
 
 
 
 Observed tumor recurrence rates for each group were as follows: SupTR group, 63.4%; GTR group, 75.3%; and STR group, 80.5% (p = 0.072). Statistically significant differences in patterns of recurrences among groups were observed with respect to local recurrence (SupTR, 57.7%; GTR, 76.0%; STR, 82.8%; p = 0.036) and distant recurrence (SupTR, 50.0%; GTR, 30.1%; STR, 23.2%; p = 0.028). Marginal recurrence showed no statistical difference between groups. Both overall survival and progression-free survival were significantly increased in the SupTR group compared with the STR and GTR groups (p < 0.0001).
 
 
 
 In this study, the authors investigated the association between EOR and patterns of recurrence in patients with IDH-wild-type GBM. The findings not only show that recurrence patterns differ according to EOR but also provide clinical evidence supporting the hypothesized mechanism by which distant recurrence occurs.


/pdf/surg-25-patterns-of-recurrences-according-to-the-extent-of-1e6y6f49.pdf

Surg-25. patterns of recurrences according to the extent of resection in parietns with glioblastoma, idh-wildtype: a retrospective study

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