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Sample records for astrocytoma

  1. Anaplastic astrocytoma.

    Science.gov (United States)

    Grimm, Sean A; Chamberlain, Marc C

    2016-07-01

    Anaplastic astrocytoma (AA) is a diffusely infiltrating, malignant, astrocytic, primary brain tumor. AA is currently defined by histology although future classification schemes will include molecular alterations. AA can be separated into subgroups, which share similar molecular profiles, age at diagnosis and median survival, based on 1p/19q co-deletion status and IDH mutation status. AA with co-deletion of chromosomes 1p and 19q and IDH mutation have the best prognosis. AA with IDH mutation and no 1p/19q co-deletion have intermediate prognosis and AA with wild-type IDH have the worst prognosis and share many molecular alterations with glioblastoma. Treatment of noncodeleted AA based on preliminary results from the CATNON clinical trial consists of maximal safe resection followed by radiotherapy with post-radiotherapy temozolomide (TMZ) chemotherapy. The role of concurrent TMZ and whether IDH1 subgroups benefit from TMZ is currently being evaluated in the recently completed randomized, prospective Phase III clinical trial, CATNON.

  2. Pilomyxoid astrocytoma of the brainstem

    Directory of Open Access Journals (Sweden)

    Marco Antonio Zanini

    2013-04-01

    Full Text Available A pilomyxoid astrocytoma is a recently described tumor that occurs predominantly in the hypothalamic-chiasmatic region and is rarely found elsewhere. It has similar features as pilocytic astrocytomas, but has distinct histological characteristics and a poorer prognosis. A pilomyxoid astrocytoma is an aggressive tumor, and increased awareness is necessary with a suspect case. We present the first case of a pilomyxoid astrocytoma of the brainstem described after the newest World Health Organization classification of central nervous system tumors.

  3. Prognostic parameters in benign astrocytomas

    DEFF Research Database (Denmark)

    Westergaard, L; Gjerris, F; Klinken, L

    1993-01-01

    To elucidate the prognosis of different types of benign astrocytomas and to ascertain whether patients with partially resected benign astrocytomas, or any subtype of these, would benefit from postoperative radiotherapy, we studied retrospectively material comprising 300 patients with benign astro...... time of patients with non-pilocytic supratentorial benign astrocytomas. The study emphasizes the necessity of a prospective combined multicenter analysis of the effect of radiation on benign astrocytomas....

  4. Prognostic parameters in benign astrocytomas

    DEFF Research Database (Denmark)

    Westergaard, L; Gjerris, F; Klinken, L

    1993-01-01

    To elucidate the prognosis of different types of benign astrocytomas and to ascertain whether patients with partially resected benign astrocytomas, or any subtype of these, would benefit from postoperative radiotherapy, we studied retrospectively material comprising 300 patients with benign...... astrocytomas treated in the period 1956 to 1991. The pilocytic type of astrocytoma was found to have an outstandingly good prognosis and should be regarded as a distinct nosological entity. For the non-pilocytic supratentorial astrocytomas, a multivariate regression analysis showed that age, tumour site...... time of patients with non-pilocytic supratentorial benign astrocytomas. The study emphasizes the necessity of a prospective combined multicenter analysis of the effect of radiation on benign astrocytomas....

  5. and astrocyte and astrocytoma cells

    DEFF Research Database (Denmark)

    Tfelt-Hansen, J.

    2008-01-01

    -transforming gene (PTTG), was found to be upregulated by the CaR in the H-500 cells, whereas calcium had no effect on PTTG expression in the U-87 astrocytoma cell line, but other proproliferative agents did upregulate PTTG in the U-87 cells. This makes PTTG a potential marker of malignancy and a therapeutic target...

  6. Retinal astrocytoma in a dog.

    Science.gov (United States)

    Kuroki, Keiichi; Kice, Nathan; Ota-Kuroki, Juri

    2017-09-01

    A miniature schnauzer dog presenting with hyphema and glaucoma of the right eye had a retinal neoplasm. Neoplastic cells stained positively for glial fibrillary acidic protein, vimentin, and S-100 and largely negatively for oligodendrocyte transcription factor 2 by immunohistochemistry. The clinical and histopathological features of canine retinal astrocytomas are discussed.

  7. Bevacizumab Therapy for Pilomyxoid Astrocytoma.

    Science.gov (United States)

    Metts, Ryan D; Bartynski, Walter; Welsh, Cynthia T; Kinsman, Stephen; Bredlau, Amy-Lee

    2017-05-01

    Pilomyxoid astrocytoma is a rare tumor of the central nervous system generally found in young children near the hypothalamus. Herein, we report a 19-month-old female infant with a pilomyxoid astrocytoma, who underwent surgery as well as carboplatin and vincristine chemotherapy in an attempt to delay radiation therapy to the brain. Magnetic resonance imaging revealed that the tumor had increased in tumor volume on therapy. Chemotherapy with carboplatin and vincristine was stopped and bevacizumab therapy (10 mg/kg every other week) was initiated. After 15 months of bevacizumab therapy, the patient's tumor was significantly smaller. Bevacizumab therapy was discontinued for 6 months due to stability in tumor size but was resumed after tumor growth was observed. Patient was again placed on bevacizumab therapy with subsequent magnetic resonance imagings revealing a decrease in tumor size.

  8. Cerebral astrocytoma in a sheep

    Science.gov (United States)

    Farjanikish, Ghasem; Khodakaram-Tafti, Azizollah; Dezfoulian, Omid

    2017-01-01

    Astrocytoma as one of the most common central nervous system (CNS) tumors is rarely reported in veterinary literature. A 7-year-old Persian Lori-Bakhtiari ewe was presented to the clinic with a two months history of progressive blindness, nystagmus to the right, bilaterally decreased pupillary reflexes, head pressing and paddling. At necropsy, a whitish well-circumscribed mass with dimensions of 3.50×2.50×1.50 cm was observed in the dorsal parietal lobe of the left cerebral hemisphere. Microscopically, the mass was well-circumscribed and highly cellular, consisted of round to elongated cells with scant and vacuolated cytoplasm with few, flaccid processes. The nuclei were round to oval with densely stippled chromatin and indistinct nucleoli. Immunohistochemical analyses showed positive staining for vimentin, S100 and glial fibrillary acidic protein. Definitive diagnosis of cerebral protoplasmic astrocytoma was made on the basis of the histopathological and immunohistochemical findings. This type of neoplasm should be included in the differential diagnosis of CNS lesions in the sheep. PMID:29085617

  9. Perinatal (fetal and neonatal) astrocytoma: a review.

    Science.gov (United States)

    Isaacs, Hart

    2016-11-01

    The purpose of this review is to document the various types of astrocytoma that occur in the fetus and neonate, their locations, initial findings, pathology, and outcome. Data are presented that show which patients are likely to survive or benefit from treatment compared with those who are unlikely to respond. One hundred one fetal and neonatal tumors were collected from the literature for study. Macrocephaly and an intracranial mass were the most common initial findings. Overall, hydrocephalus and intracranial hemorrhage were next. Glioblastoma (GBM) was the most common neoplasm followed in order by subependymal giant cell astrocytoma (SEGA), low-grade astrocytoma, anaplastic astrocytoma, and desmoplastic infantile astrocytoma (DIA). Tumors were detected most often toward the end of the third trimester of pregnancy. A number of patients were considered inoperable since their tumor occupied much of the intracranial cavity involving large areas of the brain. High-grade astrocytomas were more common than low-grade ones in this review. Fetuses and neonates with astrocytoma have a mixed prognosis ranging from as low as 20 % (GBM) to a high of 90 %. The overall survival was 47/101 or 46 %.

  10. Astrocytoma

    Science.gov (United States)

    ... Brain Tumor Facts Brain Tumor Dictionary Webinars Anytime Learning ... tissue of the brain. These tumors are “graded” on a scale from I to IV based on how normal or abnormal the cells look. ...

  11. Diffuse Infiltrating Oligodendroglioma and Astrocytoma.

    Science.gov (United States)

    van den Bent, Martin J; Smits, Marion; Kros, Johan M; Chang, Susan M

    2017-07-20

    The new 2016 WHO brain tumor classification defines different diffuse gliomas primarily according to the presence or absence of IDH mutations ( IDH-mt) and combined 1p/19q loss. Today, the diagnosis of anaplastic oligodendroglioma requires the presence of both IDH-mt and 1p/19q co-deletion, whereas anaplastic astrocytoma is divided into IDH wild-type ( IDH-wt) and IDH-mt tumors. IDH-mt tumors have a more favorable prognosis, and tumors with low-grade histology especially tend evolve slowly. IDH-wt tumors are not a homogeneous entity and warrant further molecular testing because some have glioblastoma-like molecular features with poor clinical outcome. Treatment consists of a resection that should be as extensive as safely possible, radiotherapy, and chemotherapy. Trials of patients with newly diagnosed grade II or III glioma have shown survival benefit from adding chemotherapy to radiotherapy compared with initial treatment using radiotherapy alone. Both temozolomide and the combination of procarbazine, lomustine, and vincristine provide survival benefit. In contrast, trials that compare single modality treatment of chemotherapy alone with radiotherapy alone did not observe survival differences. Currently, for patients with grade II or III gliomas who require postsurgical treatment, the preferred treatment consists of a combination of radiotherapy and chemotherapy. Low-grade gliomas with favorable characteristics are slow-growing tumors. When deciding on the timing of postsurgical treatment with radiotherapy and chemotherapy, both clinical and molecular factors should be taken into account, but a more conservative approach can be considered initially in some of these patients. The factor that best predicts benefit of chemotherapy in grade II and III glioma remains to be established.

  12. [Clinical course of a solitary retinal astrocytoma].

    Science.gov (United States)

    Töteberg-Harms, M; Paulsen, F; Duncker, G I W; Sel, S

    2009-10-01

    Retinal astrocytomas are benign tumors of the retina. Their localization can be solitary, multiple, or bilateral in both eyes. It is also known that they can be part of a phakomatosis syndrome (i.e., tuberous sclerosis or neurofibromatosis). Because retinal astrocytomas have a slow growth rate, yearly controls by an ophthalmologist with interdisciplinary consultation are adequate. Some uncommon cases have been reported in which the tumor has grown more aggressively. These tumors may require therapeutic interventions (e.g., vitreoretinal surgery, brachytherapy, photodynamic therapy, or cryotherapy).

  13. Bilateral Birdshot Retinochoroiditis and Retinal Astrocytoma

    Science.gov (United States)

    Wong, Yun; Bell, Dugald

    2017-01-01

    Background. This case highlights the importance of recognising multiple pathologies within the eye which may not necessarily be linked. Both birdshot retinochoroiditis and astrocytoma are rare conditions. The case underlines the need for early identification and treatment of birdshot retinochoroiditis with steroids and disease modifying drugs. Astrocytoma in the absence of tuberous sclerosis is also uncommon. Case Presentation. A 36-year-old male presented with 3-month history of bilateral progressive flashing lights and floaters. He was systemically well with no significant past medical history. Fundal examination revealed retinal vasculitis and active creamy lesions in the choroid radiating from the optic nerve. In the supranasal periphery of the right eye there was a raised white, jagged lesion protruding into the vitreous. Fluorescein angiogram and indocyanine green showed marked venous vasculitis, hypofluorescence, and disc leakage in keeping with birdshot retinochoroiditis. The supranasal lesion features were in keeping with astrocytoma and this was thought to be a coincidental finding. Conclusions. Retinal astrocytoma may be present as an isolated ocular finding; however, patients must still be investigated for tuberous sclerosis which is the most common association. Birdshot retinochoroiditis typically responds well to steroid therapy, and disease modifying drugs should be considered as soon as possible. PMID:28321351

  14. Current treatment of low grade astrocytoma

    DEFF Research Database (Denmark)

    Pedersen, Christina Louise; Romner, Bertil

    2013-01-01

    Through a comprehensive review of the current literature, the present article investigates several aspects of low grade astrocytomas (LGA), including prognostic factors, treatment strategies and follow-up regimes. LGA are in general relatively slow-growing primary brain tumours, but they have...

  15. Stem cells and models of astrocytomas.

    Science.gov (United States)

    Kamnasaran, Deepak

    2009-04-01

    To provide a critical assessment of current stem-cell based pre-clinical models of astrocytomas (gliomas). Data were archived from MEDLINE using Boolean formatted keyword queries. Top articles were selected for critical analyses depending on the qualitative assessment of the citation index, novelty of the findings, reputation of the research group and relevance to stem-cell based pre-clinical models of astrocytomas. The emergence of stem-cell based pre-clinical models of gliomas offers advantages for cellular transformation studies over other current in-vitro cell cultured based models. Cells utilized in these stem-cell based pre-clinical models are easier to transform, with the induced tumours demonstrating very high molecular and pathological recapitulations of astrocytomas that are derived from humans. These stem-cell based models fall into two categories. In the first, synthetic astrocytes can be differentiated from various stem cell sources such as the nervous system and embryos, and utilized in elegant forward genetic strategies to develop novel astrocytoma pre-clinical models. The second category represents a cancer stem cell pre-clinical model. In this model, glioma stem cells exhibit very high pathological recapitulations of the human tumours, and can be very informative to comprehend the basis of radio-chemoresistance among patients. The quest to develop robust pre-clinical models of astrocytomas is on an ongoing basis. The models are of clinical importance for the discovery of effective treatment modalities that can considerably improve the health of patients with this deadly disease.

  16. Pilomyxoid astrocytoma in the adult cerebellum.

    Science.gov (United States)

    Chen, Annie S; Paldor, Iddo; Tsui, Alpha E; Yuen, Tanya I

    2016-05-01

    Pilomyxoid astrocytoma (PMA) is a recently recognised World Health Organization (WHO) Grade II tumour that was previously characterised as a subtype of the WHO Grade I pilocytic astrocytoma (PA). PMA has a histological appearance distinct from PA and a poorer prognosis due to its greater propensity for local recurrence and cerebrospinal dissemination. Although originally considered a paediatric tumour involving mainly the hypothalamic and chiasmatic region, reports of the lesion occurring in the adult population and other areas of the neuroaxis are emerging. We review the literature on PMA within the adult population and present the first case of PMA in the cerebellum of an adult female. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  17. Perinatal (fetal and neonatal) astrocytoma: a review

    OpenAIRE

    Isaacs, Hart

    2016-01-01

    Introduction The purpose of this review is to document the various types of astrocytoma that occur in the fetus and neonate, their locations, initial findings, pathology, and outcome. Data are presented that show which patients are likely to survive or benefit from treatment compared with those who are unlikely to respond. Materials and methods One hundred one fetal and neonatal tumors were collected from the literature for study. Results Macrocephaly and an intracranial mass were the most co...

  18. Effects of diphenylhydantoin on murine astrocytoma radiosensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Lordo, C.D.; Stroude, E.C.; Del Maestro, R.F.

    1987-01-01

    Diphenylhydantoin is a well known anticonvulsant used primarily in the treatment of epilepsy. The prophylactic use of diphenylhydantoin has been suggested for certain cerebral metastases, and it is routinely administered to prevent seizures induced by intracranial neoplasms and/or surgery. Patients with malignant gliomas treated with diphenylhydantoin frequently receive radiation therapy. The effects of a clinical concentration of diphenylhydantoin in combination with gamma radiation was investigated using the C6 astrocytoma cell line in both monolayer and three dimensional multicellular spheroid cultures. Diphenylhydantoin at 7.2 X 10(-5) M (20 micrograms/ml) significantly increased the doubling time (23%) of the C6 astrocytoma cells in monolayer, but did not affect their survival as measured by plating efficiency. No changes were seen in spheroid growth or plating efficiency of the cells dissociated from spheroids at this concentration. Diphenylhydantoin at the clinical concentration tested was not associated with an alteration in radiation sensitivity of C6 astrocytoma cells in monolayer or three dimensional multicellular spheroid cultures.

  19. A 16-gene signature distinguishes anaplastic astrocytoma from glioblastoma.

    Directory of Open Access Journals (Sweden)

    Soumya Alige Mahabala Rao

    Full Text Available Anaplastic astrocytoma (AA; Grade III and glioblastoma (GBM; Grade IV are diffusely infiltrating tumors and are called malignant astrocytomas. The treatment regimen and prognosis are distinctly different between anaplastic astrocytoma and glioblastoma patients. Although histopathology based current grading system is well accepted and largely reproducible, intratumoral histologic variations often lead to difficulties in classification of malignant astrocytoma samples. In order to obtain a more robust molecular classifier, we analysed RT-qPCR expression data of 175 differentially regulated genes across astrocytoma using Prediction Analysis of Microarrays (PAM and found the most discriminatory 16-gene expression signature for the classification of anaplastic astrocytoma and glioblastoma. The 16-gene signature obtained in the training set was validated in the test set with diagnostic accuracy of 89%. Additionally, validation of the 16-gene signature in multiple independent cohorts revealed that the signature predicted anaplastic astrocytoma and glioblastoma samples with accuracy rates of 99%, 88%, and 92% in TCGA, GSE1993 and GSE4422 datasets, respectively. The protein-protein interaction network and pathway analysis suggested that the 16-genes of the signature identified epithelial-mesenchymal transition (EMT pathway as the most differentially regulated pathway in glioblastoma compared to anaplastic astrocytoma. In addition to identifying 16 gene classification signature, we also demonstrated that genes involved in epithelial-mesenchymal transition may play an important role in distinguishing glioblastoma from anaplastic astrocytoma.

  20. Inhibition of STAT3 reduces astrocytoma cell invasion and constitutive activation of STAT3 predicts poor prognosis in human astrocytoma.

    Directory of Open Access Journals (Sweden)

    Qinchuan Liang

    Full Text Available Astrocytoma cells characteristically possess high invasion potentials. Recent studies have revealed that knockdown of signal transducers and activators of transcription 3 (STAT3 expression by RNAi induces apoptosis in astrocytoma cell. Nevertheless, the distinct roles of STAT3 in astrocytoma's invasion and recurrence have not been elucidated. In this study, we silenced STAT3 using Small interfering RNAs in two human glioblastoma multiforme (GBM cell lines (U251 and U87, and investigated the effect on GBM cell adhesion and invasion. Our results demonstrate that disruption of STAT3 inhibits GBM cell's adhesion and invasion. Knockdown of STAT3 significantly increased E-cadherin but decreased N-cadherin, vascular endothelial growth factor, matrix metalloproteinase 2 and matrix metalloproteinase 9. Additionally, expression of pSTAT3(Tyr705 correlates with astrocytoma WHO classification, Karnofsky performance status scale score, tumor recurrence and survival. Furthermore, pSTAT3(Tyr705 is a significant prognostic factor in astrocytoma. In conclusion, STAT3 may affect astrocytoma invasion, expression of pSTAT3(Tyr705 is a significant prognostic factor in tumor recurrence and overall survival in astrocytoma patients. Therefore, STAT3 may provide a potential target for molecular therapy in human astrocytoma, and pSTAT3(Tyr705could be an important biomarker for astrocytoma prognosis.

  1. Diffuse Astrocytoma, IDH-Wildtype: A Dissolving Diagnosis.

    Science.gov (United States)

    Hasselblatt, Martin; Jaber, Mohammed; Reuss, David; Grauer, Oliver; Bibo, Annkatrin; Terwey, Stephanie; Schick, Uta; Ebel, Heinrich; Niederstadt, Thomas; Stummer, Walter; von Deimling, Andreas; Paulus, Werner

    2018-02-09

    The histological and molecular features and even the mere existence of diffuse astrocytoma, IDH-wildtype, remain unclear. We therefore examined 212 diffuse astrocytomas (grade II WHO) in adults using IDH1(R132H) immunohistochemistry followed by IDH1/IDH2 sequencing and neuroimaging review. DNA methylation status and copy number profiles were assessed by Infinium HumanMethylation450k BeadChip. Only 25/212 patients harbored tumors without IDH1/IDH2 hotspot mutations and without contrast enhancement. By DNA methylation profiling, 10/25 tumors were classified as glioblastoma, IDH-wildtype, and an additional 7 cases could not be classified using methylome analysis, but showed genetic characteristics of glioblastoma. Histologically, all of these 17 tumors were low-grade diffuse astrocytomas. Nevertheless, 10/17 patients experienced early malignant progression. Other methylation classes included diffuse midline glioma, H3 K27M-mutant, diffuse astrocytoma, IDH-mutant, pilocytic astrocytoma, and normal or reactive brain tissue (total n = 8). In conclusion, no convincing diffuse astrocytoma, IDH-wildtype, was identified. Most IDH-wildtype tumors showing histopathological and radiological features of low-grade diffuse astrocytoma exhibit molecular and clinical features of high-grade glioma and may represent an early stage of primary glioblastoma. Our findings have implications for the biology, classification and neuropathological diagnosis of diffuse astrocytoma, IDH-wildtype in adults. © 2018 American Association of Neuropathologists, Inc. All rights reserved.

  2. Pilocytic astrocytoma: A rare presentation as intraventricular tumor

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    Sattar, Sidra; Akhunzada, Naveed Z.; Javed, Gohar; Uddin, Zeeshan; Khan, Yasir A.

    2017-01-01

    Background: Pilocytic astrocytoma (PA) is the most prevalent central nervous system (CNS) tumor in pediatric population and accounts for an approximate of 5–6% of all gliomas. This neoplasm can occur at all levels of the neuraxis, with majority (67%) arising in the cerebellum and optic pathway. PAs are World Health Organization Grade I tumors and are the most benign of all astrocytomas characterized by an excellent prognosis. Other differentials include subependymal giant cell astrocytoma (SEGA), ependymoma, meningioma, and low-grade gliomas such as pilocytic or diffuse astrocytoma; calcification is more commonly regarded as a feature of benign or slow-growing tumors. Case Description: We present a case of a 17-year-old female presenting with an unusual cause of hydrocephalus, a rare case of a calcified pilocytic astrocytoma as an intraventricular tumor. Conclusion: PA rarely presents as an intraventricular tumor and should be included in the differential diagnosis of a large mass with massive intratumoral calcification. PMID:28680735

  3. Copy Number Profiling of Brazilian Astrocytomas

    Directory of Open Access Journals (Sweden)

    Lucas Tadeu Bidinotto

    2016-07-01

    Full Text Available Copy number alterations (CNA are one of the driving mechanisms of glioma tumorigenesis, and are currently used as important biomarkers in the routine setting. Therefore, we performed CNA profiling of 65 astrocytomas of distinct malignant grades (WHO grade I–IV of Brazilian origin, using array-CGH and microsatellite instability analysis (MSI, and investigated their correlation with TERT and IDH1 mutational status and clinico-pathological features. Furthermore, in silico analysis using the Oncomine database was performed to validate our findings and extend the findings to gene expression level. We found that the number of genomic alterations increases in accordance with glioma grade. In glioblastomas (GBM, the most common alterations were gene amplifications (PDGFRA, KIT, KDR, EGFR, and MET and deletions (CDKN2A and PTEN. Log-rank analysis correlated EGFR amplification and/or chr7 gain with better survival of the patients. MSI was observed in 11% of GBMs. A total of 69% of GBMs presented TERT mutation, whereas IDH1 mutation was most frequent in diffuse (85.7% and anaplastic (100% astrocytomas. The combination of 1p19q deletion and TERT and IDH1 mutational status separated tumor groups that showed distinct age of diagnosis and outcome. In silico validation pointed to less explored genes that may be worthy of future investigation, such as CDK2, DMRTA1, and MTAP. Herein, using an extensive integrated analysis, we indicated potentially important genes, not extensively studied in gliomas, that could be further explored to assess their biological and clinical impact in astrocytomas.

  4. An Achilles tendinosis masking an intramedullary astrocytoma.

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    Stappers, Jeroen; Herregods, Piet; Chappel, Rudi; Surgeloose, Didier De; Stassijns, Gaëtane

    2015-01-01

    We report the case of a 53-year-old male with a right Achilles tendinosis, who complains about a mild gait disorder starting after walking several kilometers. In the following months he develops neurological symptoms. MRI lumbar spine shows an intramedullary tumor at level Th12. A biopsy confirms the diagnosis of an intramedullary astrocytoma. Primary intramedullary tumors are relatively rare. Clinical presentation is often insidious. The authors want to make a point to reconsider a diagnosis in case it does not explain completely the anamnestic or clinical findings. According to the literature there is no optimal approach to the management of these tumors.

  5. Integrated analysis of mismatch repair system in malignant astrocytomas.

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    Irene Rodríguez-Hernández

    Full Text Available Malignant astrocytomas are the most aggressive primary brain tumors with a poor prognosis despite optimal treatment. Dysfunction of mismatch repair (MMR system accelerates the accumulation of mutations throughout the genome causing uncontrolled cell growth. The aim of this study was to characterize the MMR system defects that could be involved in malignant astrocytoma pathogenesis. We analyzed protein expression and promoter methylation of MLH1, MSH2 and MSH6 as well as microsatellite instability (MSI and MMR gene mutations in a set of 96 low- and high-grade astrocytomas. Forty-one astrocytomas failed to express at least one MMR protein. Loss of MSH2 expression was more frequent in low-grade astrocytomas. Loss of MLH1 expression was associated with MLH1 promoter hypermethylation and MLH1-93G>A promoter polymorphism. However, MSI was not related with MMR protein expression and only 5% of tumors were MSI-High. Furthermore, the incidence of tumors carrying germline mutations in MMR genes was low and only one glioblastoma was associated with Lynch syndrome. Interestingly, survival analysis identified that tumors lacking MSH6 expression presented longer overall survival in high-grade astrocytoma patients treated only with radiotherapy while MSH6 expression did not modify the prognosis of those patients treated with both radiotherapy and chemotherapy. Our findings suggest that MMR system alterations are a frequent event in malignant astrocytomas and might help to define a subgroup of patients with different outcome.

  6. Atypical imaging in a desmoplastic non-infantile astrocytoma.

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    Gupta, Abhishek; Karthigeyan, Madhivanan; Gupta, Kirti; Salunke, Pravin

    2017-03-01

    Desmoplastic infantile tumors, especially desmoplastic astrocytomas, are uncommon neoplasms that are generally seen within first 2 years of life. Their occurrence in slightly older children is very rare. The typical radiological appearance is a large cystic lesion with small enhancing solid part. In the present report, we describe a 10-year-old child with atypical appearance of desmoplastic non-infantile astrocytoma which was predominantly solid on imaging. Although rare, desmoplastic astrocytomas may present even in older children and should be considered in the differential diagnoses. These tumors may present as predominantly solid enhancing lesions and add to the radiological dilemma.

  7. Pilomyxoid Astrocytoma Occurring in the Third Ventricle

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    Sanghyeon Kim

    2015-01-01

    Full Text Available Pilomyxoid astrocytoma (PMA is a rare central nervous system tumor that has been included in the 2007 World Health Organization Classification of Tumors of the Central Nervous System. Due to its more aggressive behavior, PMA is classified as Grade II neoplasm by the World Health Organization. PMA predominantly affects the hypothalamic/chiasmatic region and occurs in children (mean age of occurrence = 10 months. We report a case of a 24-year-old man who presented with headache, nausea, and vomiting. Brain CT and MRI revealed a mass occupying only the third ventricle. We performed partial resection. Histological findings, including monophasic growth with a myxoid background, and absence of Rosenthal fibers or eosinophilic granular bodies, as well as the strong positivity for glial fibrillary acidic protein were consistent with PMA.

  8. Postoperative surveillance of pediatric cerebellar pilocytic astrocytoma.

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    Alford, Raphael; Gargan, Lynn; Bowers, Daniel C; Klesse, Laura J; Weprin, Bradley; Koral, Korgun

    2016-10-01

    The purpose of this study was to identify the optimal frequency and duration of magnetic resonance imaging follow-up in children who had gross totally resected cerebellar pilocytic astrocytomas (CPAs). Our hypothesis was that following two MR examinations, separated by at least 3 months, showing no evidence of tumor, gross totally resected CPAs did not recur and no further imaging follow-up was necessary. Retrospective review of Neuro-Oncology database from 1/2000 to 7/2013 yielded 53 patients with CPAs that had preoperative imaging and >2 years post-operative imaging follow-up available. Pilocytic astrocytomas with brainstem involvement and patients with neurofibromatosis type I were excluded. Preoperative tumor volumes were calculated. The dates and reports of the examinations were tabulated. The median number of follow-up examinations was 9 over a median follow-up time of 6.05 years (2.07-12.28 years). Two consecutive MR examinations over at least a 3 month span demonstrated the smallest negative likelihood ratio of future recurrence (0.15). There was no association of recurrence with preoperative tumor volume. Among the 35 patients with gross total resection of their tumor and greater than two negative follow-up examinations, one recurrence (2.9 %) was identified, occurring 6.4 years after initial resection. Gross totally resected pediatric CPAs can recur, but this is exceedingly rare. Frequent surveillance (every 3-6 months) is suggested in patients with CPAs until absence of tumor is concluded on imaging and documented on two consecutive studies spaced at least 3 months apart. The likelihood of recurrence thereafter is low.

  9. Mislocalization of the exitatory amino-acid transporters (EAATs in human astrocytoma and non-astrocytoma cancer cells: effect of the cell confluence

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    Varini Karine

    2012-02-01

    Full Text Available Abstract Background Astrocytomas are cancers of the brain in which high levels of extracellular glutamate plays a critical role in tumor growth and resistance to conventional treatments. This is due for part to a decrease in the activity of the glutamate transporters, i.e. the Excitatory Amino Acid Transporters or EAATs, in relation to their nuclear mislocalization in astrocytoma cells. Although non-astrocytoma cancers express EAATs, the localization of EAATs and the handling of L-glutamate in that case have not been investigated. Methods We looked at the cellular localization and activity of EAATs in human astrocytoma and non-astrocytoma cancer cells by immunofluorescence, cell fractionation and L-glutamate transport studies. Results We demonstrated that the nuclear mislocalization of EAATs was not restricted to astrocytoma and happened in all sub-confluent non-astrocytoma cancer cells we tested. In addition, we found that cell-cell contact caused the relocalization of EAATs from the nuclei to the plasma membrane in all human cancer cells tested, except astrocytoma. Conclusions Taken together, our results demonstrated that the mislocalization of the EAATs and its associated altered handling of glutamate are not restricted to astrocytomas but were also found in human non-astrocytoma cancers. Importantly, we found that a cell contact-dependent signal caused the relocalization of EAATs at the plasma membrane at least in human non-astrocytoma cancer cells, resulting in the correction of the altered transport of glutamate in such cancer cells but not in astrocytoma.

  10. Treatment of progression of diffuse astrocytoma by herbal medicine ...

    African Journals Online (AJOL)

    year-old woman who, after finishing the oncological treatment of diffuse astrocytoma, had tumour progression. Material and methods: Phytotherapy was introduced after the tumour had progressed. It consisted of 4 types of herbal medicine which ...

  11. Expression of neuronal markers, NFP and GFAP, in malignant astrocytoma.

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    Hashemi, Forough; Naderian, Majid; Kadivar, Maryam; Nilipour, Yalda; Gheytanchi, Elmira

    2014-01-01

    Immunohistochemical markers are considered as important factors in diagnosis of malignant astrocytomas. The aim of the current study was to investigate the frequency of the immunohistochemical markers neurofilament protein (NFP) and glial fibrillary acidic protein (GFAP) in malignant astrocytoma tumors in Firoozgar and Rasool-Akram hospitals from 2005 to 2010. In this cross-sectional study, immunohistochemical analysis of NFP and GFAP was performed on 79 tissue samples of patients with the diagnosis of anaplastic and glioblastoma multiform (GBM) astrocytomas. The obtained results demonstrated that all patients were positive for GFAP and only 3.8% were positive for NFP. There was no significant association between these markers and clinical, demographic, and prognostic features of patients (p>0.05). NFP was expressed only in GBMs and not in anaplastic astrocytomas. It would be crucial to confirm the present findings in a larger number of tumors, especially in high grade gliomas.

  12. Intermediate pilomyxoid astrocytoma and diencephalic syndrome: imaging findings

    Directory of Open Access Journals (Sweden)

    Olavo Kyosen Nakamura

    2012-06-01

    Full Text Available Pilomyxoid astrocytoma, an entity described as a histological variantof pilocytic astrocytoma, is a rare primary tumor of the centralnervous system. It is usually located in the hypothalamic-chiasmaticarea, affecting children with a mean age of 10 months. It has ahigh rate of recurrence and cerebrospinal fluid dissemination,which may be present throughout the neuroaxis. Due to itstopography, it may present developmental delay in childhood anddiencephalic syndrome, characterized by extreme weight loss, lackof fat accumulation, hyperactivity, euphoria and alertness. Magneticresonance imaging has an important role in its diagnosis, stagingand follow-up of pilomyxoid astrocytoma. However, for a definitivediagnosis, anatomopathology is particularly important to differentiateit from pilocytic astrocytoma. Some cases, as in this present one,have simultaneous histological features of pilocytic and pilomyxoidastrocytomas, constituting a group called intermediate pilomyxoidastrocytoma. Surgery is the best treatment option and it usuallyrequires adjuvant therapy.

  13. Juvenile Pilocytic Astrocytoma in Association with Arteriovenous Malformation

    OpenAIRE

    Soltanolkotabi, M.; Schoeneman, S.E.; Dipatri, A.J.; Hurley, M C; Ansari, S A; Rajaram, V.; Tomita, T.; Shaibani, A

    2012-01-01

    Pilocytic astrocytomas are highly vascular, relatively common primary brain tumors in the pediatric population, but their association with a true arteriovenous malformation (AVM) is extremely rare. We describe an eight-year-old girl with a right supratentorial juvenile pilocytic astrocytoma (WHO grade I) with an angiographically documented AVM entangled in the tumor mass who presented with intracranial hemorrhage due to a ruptured anterior choroidal artery pseudoaneurysm encased in the lesion...

  14. Cytologic characteristics of subependymal giant cell astrocytoma in squash smears: morphometric comparisons with gemistocytic astrocytoma and giant cell glioblastoma.

    Science.gov (United States)

    Kim, Se Hoon; Lee, Kwang-Gil; Kim, Tai Seung

    2007-01-01

    To evaluate the squash smear features of subependymal giant cell astrocytoma (SEGA) in comparison with gemistocytic astrocytoma and giant cell glioblastoma. We compared the squash smear features of 3 cases of SEGA, 9 cases of gemistocytic astrocytoma and 3 cases of giant cell glioblastoma with the morphometric findings. SEGA had, on average, a 15.84 +/- 5.03-microm nucleus, 33.22 +/- 12.05-microm cytoplasm and 0.50 +/- 0.12 nuclear/cytoplasmic ratio in squash smears. In addition, SEGA showed hairlike processes distributed along the squash direction like strap cells. While the gemistocytic astrocytoma had several tumor cells showing a vertically located nucleus, the tumor cells of SEGA showed nuclei oriented mainly in parallel. These squash cytologic features of SEGA can be very helpful in the differential diagnosis by excluding mimics.

  15. MR imaging of brain pilocytic astrocytoma: beyond the stereotype of benign astrocytoma.

    Science.gov (United States)

    Gaudino, Simona; Martucci, Matia; Russo, Rosellina; Visconti, Emiliano; Gangemi, Emma; D'Argento, Francesco; Verdolotti, Tommaso; Lauriola, Libero; Colosimo, Cesare

    2017-01-01

    Pilocytic astrocytoma (PA) is the most common pediatric brain glioma and is considered the prototype of benign circumscribed astrocytoma. Despite its low malignancy, the CT and MRI features of brain PA may resemble those of much more aggressive brain tumors. Misdiagnosis of PA is particularly easy when it demonstrates MR morphological and non-morphological findings that are inconsistent with its non-aggressive nature and that overlap with the features of more aggressive brain tumors. Basing on the evidence that the variation in the histological, genetic, and metabolic "fingerprint" for brain PA is dependent on tumor location, and the hypothesis that tumor location is related to the broad spectrum of morphological and non-morphological MR imaging findings, the authors discuss the MR imaging appearance of brain PA using a location-based approach to underline the typical and less typical imaging features and the main differential diagnosis of brain PA. A brief summary of the main pathological and clinical features, the natural history, and the treatment of brain PA is also provided. A combination of morphological and non-morphological MR imaging features and a site-based approach to differential diagnosis are required for a pre-operative diagnosis. The new "cutting-edge" MR imaging sequences have the potential to impact the ease and confidence of pediatric brain tumor interpretation and offer a more efficient diagnostic work-up. Although the typical imaging features of brain pilocytic astrocytoma make radiological diagnosis relatively easy, an atypical and more aggressive appearance can lead to misdiagnosis. Knowing the broad spectrum of imaging characteristics on conventional and advanced MR imaging is important for accurate pre-operative radiological diagnosis and correctly interpreting changes during follow-up.

  16. Transcriptional analysis of aggressiveness and heterogeneity across grades of astrocytomas.

    Science.gov (United States)

    Wang, Chunjing; Funk, Cory C; Eddy, James A; Price, Nathan D

    2013-01-01

    Astrocytoma is the most common glioma, accounting for half of all primary brain and spinal cord tumors. Late detection and the aggressive nature of high-grade astrocytomas contribute to high mortality rates. Though many studies identify candidate biomarkers using high-throughput transcriptomic profiling to stratify grades and subtypes, few have resulted in clinically actionable results. This shortcoming can be attributed, in part, to pronounced lab effects that reduce signature robustness and varied individual gene expression among patients with the same tumor. We addressed these issues by uniformly preprocessing publicly available transcriptomic data, comprising 306 tumor samples from three astrocytoma grades (Grade 2, 3, and 4) and 30 non-tumor samples (normal brain as control tissues). Utilizing Differential Rank Conservation (DIRAC), a network-based classification approach, we examined the global and individual patterns of network regulation across tumor grades. Additionally, we applied gene-based approaches to identify genes whose expression changed consistently with increasing tumor grade and evaluated their robustness across multiple studies using statistical sampling. Applying DIRAC, we observed a global trend of greater network dysregulation with increasing tumor aggressiveness. Individual networks displaying greater differences in regulation between adjacent grades play well-known roles in calcium/PKC, EGF, and transcription signaling. Interestingly, many of the 90 individual genes found to monotonically increase or decrease with astrocytoma grade are implicated in cancer-affected processes such as calcium signaling, mitochondrial metabolism, and apoptosis. The fact that specific genes monotonically increase or decrease with increasing astrocytoma grade may reflect shared oncogenic mechanisms among phenotypically similar tumors. This work presents statistically significant results that enable better characterization of different human astrocytoma grades

  17. Characterization of a novel anti-cancer compound for astrocytomas.

    Directory of Open Access Journals (Sweden)

    Sang Y Lee

    Full Text Available The standard chemotherapy for brain tumors is temozolomide (TMZ, however, as many as 50% of brain tumors are reportedly TMZ resistant leaving patients without a chemotherapeutic option. We performed serial screening of TMZ resistant astrocytoma cell lines, and identified compounds that are cytotoxic to these cells. The most cytotoxic compound was an analog of thiobarbituric acid that we refer to as CC-I. There is a dose-dependent cytotoxic effect of CC-I in TMZ resistant astrocytoma cells. Cell death appears to occur via apoptosis. Following CC-I exposure, there was an increase in astrocytoma cells in the S and G2/M phases. In in vivo athymic (nu/nu nude mice subcutaneous and intracranial tumor models, CC-I completely inhibited tumor growth without liver or kidney toxicity. Molecular modeling and enzyme activity assays indicate that CC-I selectively inhibits topoisomerase IIα similar to other drugs in its class, but its cytotoxic effects on astrocytoma cells are stronger than these compounds. The cytotoxic effect of CC-I is stronger in cells expressing unmethylated O6-methylguanine methyltransferase (MGMT but is still toxic to cells with methylated MGMT. CC-I can also enhance the toxic effect of TMZ on astrocytoma when the two compounds are combined. In conclusion, we have identified a compound that is effective against astrocytomas including TMZ resistant astrocytomas in both cell culture and in vivo brain tumor models. The enhanced cytotoxicity of CC-I and the safety profile of this family of drugs could provide an interesting tool for broader evaluation against brain tumors.

  18. Tissue thioredoxin reductase-1 expression in astrocytomas of different grades.

    Science.gov (United States)

    Esen, Hasan; Erdi, Fatih; Kaya, Bulent; Feyzioglu, Bahadır; Keskin, Fatih; Demir, Lutfi Saltuk

    2015-02-01

    Thioredoxin (Trx) is a redox active protein that regulates several physiological and biochemical functions, such as growth, apoptosis and cellular defense. The function of Trx itself is regulated by thioredoxin reductase (TrxR). Studies performed in a variety of human primary tumors have shown that thioredoxin reductase 1 (TrxR1) is overexpressed in tumoral tissues compared with corresponding normal tissues. This study was designed to determine the expression of TrxR1 in astrocytoma tissues of different World Health Organization (WHO) grades (grade I-IV). The proliferative (Ki-67) and apoptotic indices of the specimens were also investigated for correlation analysis. Astrocytoma tissues were extracted from the histopathological specimens of 40 patients. These samples included seven histologically normal brain tissues that served as a control group and ten tumoral samples for each grade of astrocytoma (grade I-IV). The histologically normal brain tissues were obtained from the non-tumoral portions of the pathological specimens of grade I (2 cases), grade II (2 cases), grade III (2 cases) and grade IV (1 case) astrocytomas. TrxR1 expression was evaluated using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunostaining. The proliferative and apoptotic indices of the specimens were investigated by Ki-67 immunostaining and TUNEL assay, respectively. TrxR1 expression, as assessed by qRT-PCR, increased significantly with astrocytoma grade (p = 0.01). The immunostaining intensity of TrxR1 in grade IV astrocytomas was significantly greater than that in the control tissue and all other astrocytoma grades (p grade III astrocytomas was significantly greater than that in the control group and grade I astrocytomas (p grades, but the differences between grade I and the control, grade II and the control, grades II and I, grades III and II were not statistically significant (p > 0.05). Ki-67 index values increased significant in accordance with grade

  19. The molecular biology of WHO grade I astrocytomas.

    Science.gov (United States)

    Marko, Nicholas F; Weil, Robert J

    2012-12-01

    World Health Organization (WHO) grade I astrocytomas include pilocytic astrocytoma (PA) and subependymal giant cell astrocytoma (SEGA). As technologies in pharmacologic neo-adjuvant therapy continue to progress and as molecular characteristics are progressively recognized as potential markers of both clinically significant tumor subtypes and response to therapy, interest in the biology of these tumors has surged. An updated review of the current knowledge of the molecular biology of these tumors is needed. We conducted a Medline search to identify published literature discussing the molecular biology of grade I astrocytomas. We then summarized this literature and discuss it in a logical framework through which the complex biology of these tumors can be clearly understood. A comprehensive review of the molecular biology of WHO grade I astrocytomas is presented. The past several years have seen rapid progress in the level of understanding of PA in particular, but the molecular literature regarding both PA and SEGA remains nebulous, ambiguous, and occasionally contradictory. In this review we provide a comprehensive discussion of the current understanding of the chromosomal, genomic, and epigenomic features of both PA and SEGA and provide a logical framework in which these data can be more readily understood.

  20. Microscopic thrombi in anaplastic astrocytoma predict worse survival?

    Science.gov (United States)

    Prayson, Nicholas F; Koch, Paul; Angelov, Lilyana; Prayson, Richard A

    2011-12-01

    The purpose of this study is to determine whether anaplastic astrocytoma patients with intratumoral vascular thrombi have a worse survival than anaplastic astrocytoma patients without thrombi. A retrospective review of 101 patients (60 males; mean age, 53.3 years) with anaplastic astrocytoma (World Health Organization grade III) was conducted. Thrombi were counted relative to the number of involved blood vessels in the initially resected tumor (69 biopsies, 32 subtotal resections) and were correlated with survival and development of postoperative deep venous thrombosis (DVT). Of tumors with thrombi (n = 17), the percentage of blood vessels with thrombi ranged from 1.5% to 20% (mean, 5.6%). Of these patients, 16 died of tumor (mean survival, 15.4 months), and 1 patient was alive with tumor at 180 months. Eighty-four patients with anaplastic astrocytoma had no intravascular tumor thrombi; 75 of these patients died of tumor (mean survival, 26.5 months), 4 patients were alive, and 5 patients were lost to follow-up. Evidence of DVT was found in 2 (18.2%) of 11 tested patients with thrombi vs 10 (18.5%) of 54 patients without thrombi. Patients with microscopic intratumoral thrombi (17% of anaplastic astrocytoma) had a worse survival compared with patients without thrombi; the difference did not reach statistical significance. There was no correlation between the presence of intratumoral thrombi and the development of DVT. Copyright © 2011 Elsevier Inc. All rights reserved.

  1. Cerebral Pilocytic Astrocytoma with Spontaneous Intracranial Hemorrhage in Adults

    Directory of Open Access Journals (Sweden)

    Hao-Ming Li

    2008-11-01

    Full Text Available Pilocytic astrocytomas are found predominantly in the pediatric population; reports of these tumors are extremely rare in adults. We report 2 cases of adult pilocytic astrocytoma with intracranial hemorrhage. A 32-year-old male presented with neck stiffness and severe headache, and a 34-year-old male was referred for headache and double vision. Computed tomography (CT and magnetic resonance imaging (MRI revealed a well-enhanced and circumscribed cystic hemorrhagic tumor with mural nodule over the cerebral hemisphere region. Perfusion-weighted MRI (PWI was also performed in both patients. The measured relative cerebral blood volume ratios of the mural nodules in these 2 cases were, respectively, 1.34 and 2.81 when compared with normal white matter. After surgical resection, microscopic examination of the lesions showed pilocytic astrocytomas. Since pilocytic astrocytoma and other cystic tumors with mural nodule (such as hemangioblastoma have similar findings on conventional CT and MRI, PWI is helpful in the differential diagnosis. The literature on hemorrhagic pilocytic astrocytoma is also reviewed.

  2. Multiple solid pilocytic astrocytomas in cerebleiium with neurofibromatosis type: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Seo Young; Kim, Myung Soon; Kim, Young Ju [Dept. of Radiology, Yonsei University Wonju College of Medicine, Wonju Severance Christian Hospital, Wonju (Korea, Republic of)

    2014-02-15

    Pilocytic astrocytoma usually has a classic imaging manifestation of a solitary, cyst-like mass with a strong contrast-enhancing mural nodule. There is only one published report so far of multiple solid and cyst type pilocytic astrocytomas in the cerebellum in neurofibromatosis type 1 (NF1) patient from the United States in 2007. We report a case of pilocytic astrocytoma presenting with only solid, multiple pilocytic astrocytomas in the cerebellum in NF1 patient.

  3. GFAPδ/GFAPα ratio directs astrocytoma gene expression towards a more malignant profile

    NARCIS (Netherlands)

    Stassen, Oscar M J A; van Bodegraven, Emma J.; Giuliani, Fabrizio; Moeton, Martina; Kanski, Regina; Sluijs, Jacqueline A.; van Strien, Miriam E.; Kamphuis, Willem; Robe, Pierre A.J.; Hol, Elly M.

    2017-01-01

    Astrocytomas are the most common malignant brain tumours and are to date incurable. It is unclear how astrocytomas progress into higher malignant grades. The intermediate filament cytoskeleton is emerging as an important regulator of malignancy in several tumours. The majority of the astrocytomas

  4. TOTAL REGRESSION OF ACQUIRED RETINAL ASTROCYTOMA USING PHOTODYNAMIC THERAPY.

    Science.gov (United States)

    House, Robert J; Mashayekhi, Arman; Shields, Jerry A; Shields, Carol L

    2016-01-01

    To report successful treatment of a fine-needle aspiration biopsy-proven acquired retinal astrocytoma with photodynamic therapy. Case report. A 50-year-old man complaining of decreased vision of his right eye was found to have a visual acuity of 20/100 and an amelanotic juxtapapillary retinal tumor with surrounding subretinal fluid and lipid exudation extending into the fovea. Fine-needle aspiration biopsy showed an astrocytic lesion consistent with retinal astrocytoma. The lesion was treated with one session of photodynamic therapy. At 20 months after photodynamic therapy, visual acuity had improved to 20/20 with complete tumor regression and normal foveal contour on optical coherence tomography. This report confirms that photodynamic therapy of symptomatic acquired retinal astrocytoma may be effective in causing tumor regression and stabilizing or improving visual acuity by reducing tumor leakage.

  5. Differential proteomics analysis of low- and high-grade of astrocytoma using iTRAQ quantification

    Science.gov (United States)

    Ren, Tong; Lin, Shide; Wang, Zhongfeng; Shang, Aijia

    2016-01-01

    Astrocytoma is one of the most common types of brain tumor, which is histologically and clinically classified into four grades (I–IV): I (pilocytic astrocytoma), II (diffuse astrocytoma), III (anaplastic astrocytoma), and IV (glioblastoma multiforme). A higher grade astrocytoma represents a worse prognosis and is more aggressive. In this study, we compared the differential proteome profile of astrocytoma from grades I to IV. The protein samples from clinical specimens of grades I, II, III, and IV astrocytoma were analyzed by two-dimensional liquid chromatography–tandem mass spectrometry and isobaric tags for relative and absolute quantitation and quantification. A total of 2,190 proteins were identified. Compared to grade I astrocytoma, 173 (12.4%), 304 (14%), and 462 (21.2%) proteins were aberrantly expressed in grades II, III, and IV, respectively. By bioinformatics analysis, the cell proliferation, invasion, and angiogenesis-related pathways increase from low- to high-grade of astrocytoma. Five differentially expressed proteins were validated by Western blot. Within them, matrix metalloproteinase-9 and metalloproteinase inhibitor 1 were upregulated in glioblastoma multiforme group; whereas fibulin-2 and -5 were downregulated in grade II/III/IV astrocytoma, and the negative expression was significantly associated with advanced clinical stage. Functional analysis showed that both fibulin-2 and -5 may exert an antitumor effect by inhibiting cell proliferation, in vitro migration/invasion in glioma cells. New molecular biomarkers are likely to be used for accurate classification of astrocytoma and likely to be the target for drug development. PMID:27713642

  6. Long-Term Sequelae after Cerebellar Astrocytoma Surgery

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2004-05-01

    Full Text Available The long-term effects on neurologic, neuropsychological, and behavioral functioning in a consecutive series of 23 children treated surgically for cerebellar pilocytic astrocytoma without additional radio- and chemotherapy are determined in a study at Sophia Children’s Hospital, Rotterdam, The Netherlands, and other medical centers.

  7. Malignant astrocytoma in elderly patients: where do we stand?

    Science.gov (United States)

    Tabatabai, Ghazaleh; Stupp, Roger; Wick, Wolfgang; Weller, Michael

    2013-12-01

    Age is inversely correlated with clinical outcome and a strong prognostic factor for the course of most primary brain tumors including malignant astrocytoma, i.e. anaplastic astrocytoma and glioblastoma. We here review available clinical outcome data and discuss future directions of clinical research. The standard of care in patients with malignant astrocytoma above the range of 65-70 years was considered radiotherapy, preferentially using a hypofractionated regimen (15 × 2.66 Gy). Two phase III clinical trials, the NOA-08 and Nordic trials, demonstrated that temozolomide (TMZ) therapy alone was not inferior to radiotherapy alone, and methylation of the O-methylguanine-DNA-methyltransferase (MGMT) gene promoter was predictive with a methylated MGMT promoter indicating a benefit from TMZ chemotherapy. Ongoing clinical trials in this patient population include the National Cancer Institute of Canada/European Organisation for Research and Treatment of Cancer intergroup trial, investigating the combination of hypofractionated radiotherapy and TMZ chemotherapy, and the Swiss ARTE trial, investigating the combination of bevacizumab and hypofractionated radiotherapy. Recent translational studies indicate that prognostically favorable factors in malignant astrocytoma from younger patients are virtually absent in the elderly. Current standard of care for elderly patients with malignant astrocytoma involves a treatment strategy based on the MGMT gene promoter methylation status. The role of combined radiotherapy and TMZ chemotherapy and a potential role for the addition of anti-VEGF therapy to radiotherapy are currently addressed in ongoing trials. The lack of favorable prognostic factors in tumor tissue might in part explain the poorer clinical outcome of elderly patients.

  8. Circulating microRNAs as Biomarkers for Pediatric Astrocytomas.

    Science.gov (United States)

    López-Aguilar, Javier Enrique; Velázquez-Flores, Miguel A; Simón-Martínez, Luis A; Ávila-Miranda, Richard; Rodríguez-Florido, Marco A; Ruiz-Esparza Garrido, Ruth

    2017-05-01

    Since MicroRNAs (miRNAs) are potent regulators of gene expression, their expression and function alterations are associated with different types of cancer, including pediatric astrocytoma. Since the secretion of miRNAs by tumors into corporal fluids has made it possible to identify biomarkers in cancer, their deter mination in pediatric astrocytoma is vital. In order to gain insight into the mechanisms controlled by miRNAs in these neoplasms, we tested the expression of miRNAs 130a, 145, 335, 1303, and let-7g-3p by qPCR in tumors and blood serum from pediatric patients with astrocytoma. The data was analyzed with the DIANA-miRPath v3.0 platform. The data represented expression changes of all mirRNAs tested in both tumors and blood serum, which strongly suggest their use as circulating biomarkers for astrocytic tumors. The bioinformatic analysis -with DIANA-miRPath v3.0- showed the involvement of these miRNAs in extracellular matrix (ECM)-receptor interaction and proteoglycans in cancer, which control many hallmarks of cancer. In fact, the expression of the proteoglycan syndecan 4 (SDC4) and that of its biosynthetic enzymes, Exostosin Glycosyltransferase 1 (EXT1) and Xylosyltransferase 1 (XYLT1), were altered in pediatric astrocytoma. Our results highlight the role of microRNAs in the biology of pediatric astrocytoma and demonstrated for the first time the potential use of some circulating microRNAs as non-invasive biomarkers for this type of tumors, particularly miRs 130a, 145, and 335. Copyright © 2017 IMSS. Published by Elsevier Inc. All rights reserved.

  9. Anorexia: an early sign of fourth ventricle astrocytoma in children.

    Science.gov (United States)

    Leroy, Henri-Arthur; Baroncini, Marc; Delestret, Isabelle; Florent, Vincent; Vinchon, Matthieu

    2014-12-01

    Paediatric low-grade astrocytomas of the fourth ventricle are rare tumours, generally revealed by hydrocephalus. However, some patients present with a history of severe anorexia. It might be a harbinger, which if recognized, could lead to earlier diagnosis. We decided to examine our database in order to evaluate the incidence and signification of anorexia in this context. Retrospective monocentric study of cases of low-grade astrocytomas of the fourth ventricle operated between 1991 and 2012 in our paediatric neurosurgery department. We particularly observed the clinical presentation and long-term clinical, oncological and radiological evolution. Non-parametrical tests were used (Mann-Whitney, Fisher). We reviewed 34 cases, 31 pilocytic astrocytomas and 3 diffuse astrocytomas, 16 boys and 18 girls, (M/F ratio 0.89). Mean age at diagnosis was 8 years old. Seven presented with notable anorexia, the average BMI in this group was ≤2 standard deviation (SD); with clinical signs evolving for 11.5 months. Twenty-seven children had no anorexia; average BMI in this group was +1 SD, with clinical evolution for 6 months on an average of p anorexia, body mass index improved markedly in the postoperative follow-up, which lasted, on average, for 6 years. Anorexia with stunted body weight curve is a non-exceptional presentation in children with low-grade astrocytomas of the fourth ventricle. Unexplained or atypical anorexia with negative etiologic assessment should prompt cerebral imaging. Clinical improvement after surgical resection, could suggest a possible interaction between tumour tissue and appetite-suppressing peptide secretion.

  10. Neurotrophin receptors expression and JNK pathway activation in human astrocytomas

    Directory of Open Access Journals (Sweden)

    Maraziotis Theodore

    2007-10-01

    Full Text Available Abstract Background Neurotrophins are growth factors that regulate cell growth, differentiation and apoptosis in the nervous system. Their diverse actions are mediated through two different transmembrane – receptor signaling systems: Trk receptor tyrosine kinases (TrkA, TrkB, TrkC and p75NTR neurotrophin receptor. Trk receptors promote cell survival and differentiation while p75NTR induces, in most cases, the activity of JNK-p53-Bax apoptosis pathway or suppresses intracellular survival signaling cascades. Robust Trk activation blocks p75NTR -induced apoptosis by suppressing the JNK-p53-Bax pathway. The aim of this exploratory study was to investigate the expression levels of neurotrophin receptors, Trks and p75NTR, and the activation of JNK pathway in human astrocytomas and in adjacent non-neoplastic brain tissue. Methods Formalin-fixed paraffin-embedded serial sections from 33 supratentorial astrocytomas (5 diffuse fibrillary astrocytomas, WHO grade II; 6 anaplastic astrocytomas, WHO grade III; 22 glioblastomas multiforme, WHO grade IV were immunostained following microwave pretreatment. Polyclonal antibodies against TrkA, TrkB, TrkC and monoclonal antibodies against p75NTR and phosphorylated forms of JNK (pJNK and c-Jun (pc-Jun were used. The labeling index (LI, defined as the percentage of positive (labeled cells out of the total number of tumor cells counted, was determined. Results Moderate to strong, granular cytoplasmic immunoreactivity for TrkA, TrkB and TrkC receptors was detected in greater than or equal to 10% of tumor cells in the majority of tumors independently of grade; on the contrary, p75NTR receptor expression was found in a small percentage of tumor cells (~1% in some tumors. The endothelium of tumor capillaries showed conspicuous immunoreactivity for TrkB receptor. Trk immunoreactivity seemed to be localized in some neurons and astrocytes in non-neoplastic tissue. Phosphorylated forms of JNK (pJNK and c-Jun (pc-Jun were

  11. Juvenile pilocytic astrocytoma in association with arteriovenous malformation.

    Science.gov (United States)

    Soltanolkotabi, M; Schoeneman, S E; Dipatri, A J; Hurley, M C; Ansari, S A; Rajaram, V; Tomita, T; Shaibani, A

    2012-06-01

    Pilocytic astrocytomas are highly vascular, relatively common primary brain tumors in the pediatric population, but their association with a true arteriovenous malformation (AVM) is extremely rare. We describe an eight-year-old girl with a right supratentorial juvenile pilocytic astrocytoma (WHO grade I) with an angiographically documented AVM entangled in the tumor mass who presented with intracranial hemorrhage due to a ruptured anterior choroidal artery pseudoaneurysm encased in the lesion. The AVM nidus as well as the hemorrhage site was embolized with Onyx. A literature review revealed only one previous report of a true intermixture of these two lesions. We hypothesize whether the association of vascular malformations and primary brain tumors are merely coincidental or if they point to the existence of a distinct entity and/or a common etiologic factor.

  12. Pilocytic Astrocytoma Enlargement Following Irradiation: Relapse or Pseudoprogression?

    Science.gov (United States)

    Golanov, Andrey V.; Kostjuchenko, Valery V; Galkin, Mikhail; Konovalov, Alexander N

    2017-01-01

    Pilocytic astrocytomas are the most common gliomas (World Health Organization (WHO) grade 1) in children. According to many authors, stereotactic irradiation (radiotherapy and radiosurgery) is an effective method that provides a prolonged, recurrence-free survival in patients who have had partial tumor removal or in patients with an unresectable tumor. We present a case of a patient with midbrain pilocytic astrocytoma that enlarged considerably in the first six months after irradiation and then diminished in size during the next six months without any antitumor treatment. The clinical and radiological follow-up data for this patient, the surgery results for similar patients, and the data from other authors led us to the conclusion that early tumor volume enlargement after irradiation is usually pseudoprogression. PMID:28367384

  13. {sup 201}Thallium SPECT, accuracy in astrocytoma diagnosis and treatment evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Kaellen, K

    1999-10-01

    The aims of the studies included in this thesis were: - to investigate the reliability of {sup 201}Thallium single photon emission computed tomography. Tl SPECT for preoperative diagnosis and histological staging of malignant astrocytomas in comparison with CT; - to develop a method for quantification of cerebral thallium uptake, and to evaluate the quantitative measurement in comparison with CT, for astrocytoma treatment follow-up purposes; - to compare quantitative Tl SPECT and proton magnetic resonance spectroscopy (H-MRS) with conventional MR imagingfor astrocytoma monitoring, and to evaluate associations between change of morphological tumour characteristics during treatment and changes of cerebral thallium uptake and metabolic ratios. Results and conclusions: - High TI-index, calculated as a ratio comparing tumour uptake to uptake in the contralateral hemisphere, is an indicator of highly malignant astrocytoma. Differentiation between the high-grade astrocytomas, the low-grade astrocytomas, and infectious lesions is only partial, with an overlap of Tl-indexes between these groups. High-grade astrocytomas that do not show contrast enhancement on CT, and astrocytomas with central necrosis and moderate ring-enhancement, tend to be underestimated when evaluated by Tl-index calculation. Tl SPECT is not a reliable method for non-invasive tumour staging among the group of highly malignant astrocytomas. - Quantification of cerebral TI-uptake, defining the volume of viable tumour tissue, is a new method for astrocytoma chemotherapy monitoring. Results suggest that the method provides prognostic information, and information of treatment efficacy, at an earlier stage than CT. - We did not find a higher accuracy of quantitative Tl SPECT than of MR for monitoring purposes and our results indicated that treatment induced MR changes were interrelated with TI-uptake variations. - Multi-voxel H-MRS was difficult to apply for astrocytoma treatment monitoring, due to the

  14. Astrocytoma of the pituitary gland (pituicytoma): case report

    Energy Technology Data Exchange (ETDEWEB)

    Uesaka, T.; Miyazono, M.; Nishio, S. [Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka (Japan); Iwaki, T. [Department of Neuropathology, Graduate School of Medical Sciences, Kyushu University (Japan)

    2002-02-01

    A 34-year-old man presented with a 4-month history of visual obscuration. Magnetic resonance imaging showed a solid, discrete, contrast-enhancing pituitary mass with suprasellar extension. Surgery, which was performed via a transsphenoidal approach, disclosed the pituitary tumor to be a fibrillary astrocytoma (pituicytoma). This case report contains the clinical and neuroimaging features of this rare tumor of the neurohypophysis, which masqueraded as a pituitary adenoma. (orig.)

  15. Effect of cognitive rehabilitation in a case of thalamic astrocytoma.

    Science.gov (United States)

    Lo Buono, Viviana; Corallo, Francesco; De Cola, Maria Cristina; Chillemi, Antonino; Grugno, Rosario; Bramanti, Placido; Marino, Silvia

    2016-01-01

    We describe the effectiveness of rehabilitative training for a neuropsychological deficit following the removal and treatment of a fibrillary astrocytoma (Grade II) in a young man. The rehabilitative training was based on cognitive and motivational techniques and has been carried out for a period of 3 months (2 times per week). The results, even if limited to a single case, seem to support the idea that cognitive rehabilitation should facilitate the brain's reorganization of basic cognitive functions in the neuro-oncologic field.

  16. Clinical prognostic factors in adults with astrocytoma: Historic cohort.

    Science.gov (United States)

    Wegman-Ostrosky, Talia; Reynoso-Noverón, Nancy; Mejía-Pérez, Sonia I; Sánchez-Correa, Thalía E; Alvarez-Gómez, Rosa María; Vidal-Millán, Silvia; Cacho-Díaz, Bernardo; Sánchez-Corona, José; Herrera-Montalvo, Luis A; Corona-Vázquez, Teresa

    2016-07-01

    To explore the clinical prognostic factors for adults affected with astrocytoma. Using a historic cohort, we selected 155 clinical files from patients with astrocytoma using simple randomization. The main outcome variable was overall survival time. To identify clinical prognostic factors, we used bivariate analysis, Kaplan Meier, the log rank test and the Cox regression models. The number of lost years lived with disability (DALY) based on prevalence, was calculated. The mean age at diagnosis was 45.7 years. Analysis according to tumour stage, including grades II, III and IV, also showed a younger age of presentation. Kaplan-Meier survival estimates showed that tumour grade, Karnofsky status (KPS) ≥70, resection type, chemotherapy, radiotherapy, alcohol consumption, familial history of cancer and clinical presentation were significantly associated with survival time. Using a proportional hazard model, age, grade IV, resection, chemotherapy+radiotherapy and KPS were identified as prognostic factors.The amount of life lost due to premature death in this population was 28 years. In our study, astrocytoma was diagnosed in young adults. The overall survival was 15 months, 9% (n=14) of patients presented a survival of 2 years, and 3% of patients survived 3 years. On average the number of years lost due to premature death and disability was 28.53 years. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Anticancer activity of glucomoringin isothiocyanate in human malignant astrocytoma cells.

    Science.gov (United States)

    Rajan, Thangavelu Soundara; De Nicola, Gina Rosalinda; Iori, Renato; Rollin, Patrick; Bramanti, Placido; Mazzon, Emanuela

    2016-04-01

    Isothiocyanates (ITCs) released from their glucosinolate precursors have been shown to inhibit tumorigenesis and they have received significant attention as potential chemotherapeutic agents against cancer. Astrocytoma grade IV is the most frequent and most malignant primary brain tumor in adults without any curative treatment. New therapeutic drugs are therefore urgently required. In the present study, we investigated the in vitro antitumor activity of the glycosylated isothiocyanate moringin [4-(α-l-rhamnopyranosyloxy)benzyl isothiocyanate] produced from quantitative myrosinase-induced hydrolysis of glucomoringin (GMG) under neutral pH value. We have evaluated the potency of moringin on apoptosis induction and cell death in human astrocytoma grade IV CCF-STTG1 cells. Moringin showed to be effective in inducing apoptosis through p53 and Bax activation and Bcl-2 inhibition. In addition, oxidative stress related Nrf2 transcription factor and its upstream regulator CK2 alpha expressions were modulated at higher doses, which indicated the involvement of oxidative stress-mediated apoptosis induced by moringin. Moreover, significant reduction in 5S rRNA was noticed with moringin treatment. Our in vitro results demonstrated the antitumor efficacy of moringin derived from myrosinase-hydrolysis of GMG in human malignant astrocytoma cells. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Transcriptome analysis reveals distinct gene expression profiles in astrocytoma grades II-IV.

    Science.gov (United States)

    Narsia, Nato; Ramagiri, Pradeep; Ehrmann, Jiri; Kolar, Zdenek

    2017-09-01

    Astrocytoma is the most prevalent form of primary brain cancer categorized into four histological grades by the World Health Organization. Investigation into individual grades of astrocytoma by previous studies has provided some insight into dysregulation of regulatory networks associated with increasing astrocytoma grades. However, further understanding of key mechanisms that distinguish different astrocytoma grades is required to facilitate targeted therapies. In this study, we utilized a large cohort of publicly available RNA sequencing data from patients with diffuse astrocytoma (grade II), anaplastic astrocytoma (grade III), primary glioblastoma (grade IV), secondary glioblastoma (grade IV), recurrent glioblastoma (grade IV), and normal brain samples to identify genetic similarities and differences between these grades using bioinformatics applications. Our analysis revealed a distinct gene expression pattern between grade II astrocytoma and grade IV glioblastoma (GBM). We also identified genes that were exclusively expressed in each of the astrocytoma grades. Furthermore, we identified known and novel genes involved in key pathways in our study. Gene set enrichment analysis revealed a distinct expression pattern of transcriptional regulators in primary GBM. Further investigation into molecular processes showed that the genes involved in cell proliferation and invasion were shared across all subtypes of astrocytoma. Also, the number of genes involved in metastasis, regulation of cell proliferation, and apoptosis increased with tumor grade. We confirmed existing findings and shed light on some important genes and molecular processes that will improve our understanding of glioma biology.

  19. Potential Utility of Visually AcceSAble Rembrandt Images Assessment in Brain Astrocytoma Grading.

    Science.gov (United States)

    Yu, Jing; Wang, Min; Song, Jiacheng; Huang, DongYa; Hong, Xunning

    2016-01-01

    The aim of this study was to evaluate the predictive value of multivariate factors of Visually AcceSAble Rembrandt Images (VASARI) in brain astrocytoma grading. Presurgical magnetic resonance images of 126 patients with brain astrocytomas (World Health Organization grade 2, n = 38; grade 3, n = 36; grade 4, n = 52) were rated by 2 neuroradiologists for tumor size, location, and tumor morphology by using a standardized imaging feature set VASARI. Significant differences were noted in 12 factors of VASARI including enhancement quality, enhancing proportion, noncontrast enhancing tumor proportion, necrosis proportion, edema proportion, hemorrhage, thickness of enhancing margin, definition of the enhancing margin, pial and ependymal invasion, enhanced tumor crossing midline, and satellites between brain astrocytoma grades (grades 1-IV, P astrocytoma, whereas edema proportion was an independent diagnostic factor in differentiating grade 2 and grade 3. Noncontrast enhancing tumor proportion was a predictive factor in the diagnosis of grade 4 astrocytoma. Receiver operating characteristic analysis illustrates edema proportion score higher than 2 with sensitivity of 86.1% in differentiating grade 2 and grade 3 astrocytoma. Noncontrast enhancing tumor proportion scores 4 or lower has high sensitivity (92.3%) but moderate specificity (50.0%) in differentiating grade 3 and grade 4 astrocytoma. Our data illustrate that magnetic resonance features of VASARI especially enhancement quality, edema proportion, and noncontrast enhancing tumor proportion provided precise and detailed information of astrocytoma grading and suggested that prediction of astrocytoma grading is based on VASARI as an adjunct to biopsy.

  20. Expression of the lysosomal-associated membrane protein-1 (LAMP-1) in astrocytomas

    DEFF Research Database (Denmark)

    Jensen, Stine Skov; Christensen, Karina; Aaberg-Jessen, Charlotte

    recently been suggested to possess innate resistance mechanisms against radiation and chemotherapy possibly explaining the high level of therapeutic resistance of these tumors. Since the presence and distribution of lysosomes in tumor cells and especially in tumor stem cells in astrocytomas is unknown......, the aim of this study was to investigate the immunohistochemical expression of LAMP-1, a membrane bound protein in lysosomes, in formalin fixed paraffin embedded tumor tissue from 23 diffuse astrocytomas, 17 anaplastic astrocytomas and 72 glioblastomas. The LAMP-1 expression was scored and compared...... cells, cell clusters and in blood vessel endothelial cells. The LAMP-1 expression in glioblastomas was significantly higher than in diffuse and anaplastic astrocytomas (p

  1. Overexpression of Fli-1 in astrocytoma is associated with poor prognosis.

    Science.gov (United States)

    Tsai, Hung-Pei; Tsai, Tai-Hsin; Hsieh, Ya-Ju; Chen, Yi-Ting; Lee, Chih-Ling; Tsai, Yi-Cheng; She, Ting-Chang; Lin, Chih-Lung; Chai, Chee-Yin; Kwan, Aij-Lie

    2017-04-25

    Astrocytoma, a common and highly malignant type of brain tumor, is associated with poor overall survival despite advances in surgical treatment, radiotherapy, and chemotherapy. The nuclear transcription factor Fli-1 has been shown to increase cellular proliferation and tumorigenesis in many types of cancer; however, previous reports have not described a correlation between clinical outcomes and Fli-1 in astrocytoma patients. The present study aimed to elucidate the clinical role of Fli-1 in astrocytoma. High-level of Fli-1 protein expression was significantly association with World Health Organization (WHO) high grade and poor prognosis. A multivariate analysis revealed that the WHO grade and Fli-1 protein expression were independent factor of prognostic factors of patients with astrocytoma. In addition, Fli-1 silencing inhibited proliferation, migration, and invasion and led to the downregulation of Ki-67, VEGF, and cyclin D1 expression in the astrocytoma cells. Fli-1 protein expression in astrocytoma tissue samples were detected via immunohistochemistry, and potential correlations between clinical parameters and Fli-1 expression were assessed in patients with astrocytoma. Additionally, proliferation, invasion, and migration assays of astrocytoma cell lines were conducted to evaluate the effects of short interfering RNA (siRNA) on these processes; in addition, these cells were subjected to western blotting to detect the expression levels of Fli-1, Ki-67, VEGF, and Cyclin D1. Fli-1 shows promise as a potential prognostic biomarker and therapeutic molecular target for astrocytoma patients.

  2. Familial melanoma-astrocytoma syndrome: synchronous diffuse astrocytoma and pleomorphic xanthoastrocytoma in a patient with germline CDKN2A/B deletion and a significant family history

    Science.gov (United States)

    Chan, Andrew K.; Han, Seunggu J.; Choy, Winward; Beleford, Daniah; Aghi, Manish K.; Berger, Mitchel S.; Shieh, Joseph T.; Bollen, Andrew W.; Perry, Arie; Phillips, Joanna J.; Butowski, Nicholas; Solomon, David A.

    2017-01-01

    Familial melanoma-astrocytoma syndrome is a tumor predisposition syndrome caused by inactivating germline alteration of the CDKN2A tumor suppressor gene on chromosome 9p21. While some families with germline CDKN2A mutations are prone to development of just melanomas, other families develop both melanomas, astrocytomas, and occasionally other nervous-system neoplasms including peripheral nerve sheath tumors and meningiomas. The histologic spectrum of the astrocytomas that arise as part of this syndrome is not well described, nor are the additional genetic alterations that drive these astrocytomas apart from the germline CDKN2A inactivation. Herein, we report the case of a young man with synchronous development of a pleomorphic xanthoastrocytoma, diffuse astrocytoma, and paraspinal mass radiographically consistent with a peripheral nerve sheath tumor. His paternal family history is significant for melanoma, glioblastoma, and oral squamous cell carcinoma. Genomic profiling revealed that he harbors a heterozygous deletion in the germline of chromosome 9p21.3 encompassing the CDKN2A and CDKN2B tumor suppressor genes. Both the pleomorphic xanthoastrocytoma and diffuse astrocytoma were found to have homozygous deletion of CDKN2A/B due to somatic loss of the other copy of chromosome 9p containing the remaining intact alleles. Additional somatic alterations included BRAF p.V600E mutation in the pleomorphic xanthoastrocytoma and PTPN11, ATRX, and NF1 mutations in the diffuse astrocytoma. The presence of germline CDKN2A/B inactivation together with the presence of multiple anatomically, histologically, and genetically distinct astrocytic neoplasms, both with accompanying somatic loss of heterozygosity for the CDKN2A/B deletion, led to a diagnosis of familial melanoma-astrocytoma syndrome. This remarkable case illustrates the histologic and genetic diversity that astrocytomas arising as part of this rare glioma predisposition syndrome can demonstrate. PMID:28699883

  3. Nitroproteins in Human Astrocytomas Discovered by Gel Electrophoresis and Tandem Mass Spectrometry

    Science.gov (United States)

    Peng, Fang; Li, Jianglin; Guo, Tianyao; Yang, Haiyan; Li, Maoyu; Sang, Shushan; Li, Xuejun; Desiderio, Dominic M.; Zhan, Xianquan

    2015-12-01

    Protein tyrosine nitration is involved in the pathogenesis of highly fatal astrocytomas, a type of brain cancer. To understand the molecular mechanisms of astrocytomas and to discover new biomarkers/therapeutic targets, we sought to identify nitroproteins in human astrocytoma tissue. Anti-nitrotyrosine immunoreaction-positive proteins from a high-grade astrocytoma tissue were detected with two-dimensional gel electrophoresis (2DGE)-based nitrotyrosine immunoblots, and identified with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Fifty-seven nitrotyrosine immunopositive protein spots were detected. A total of 870 proteins (nitrated and non-nitrated) in nitrotyrosine-immunopositive 2D gel spots were identified, and 18 nitroproteins and their 20 nitrotyrosine sites were identified with MS/MS analysis. These nitroproteins participate in multiple processes, including drug-resistance, signal transduction, cytoskeleton, transcription and translation, cell proliferation and apoptosis, immune response, phenotypic dedifferentiation, cell migration, and metastasis. Among those nitroproteins that might play a role in astrocytomas was nitro-sorcin, which is involved in drug resistance and metastasis and might play a role in the spread and treatment of an astrocytoma. Semiquantitative immune-based measurements of different sorcin expressions were found among different grades of astrocytomas relative to controls, and a semiquantitative increased nitration level in high-grade astrocytoma relative to control. Nitro-β-tubulin functions in cytoskeleton and cell migration. Semiquantitative immunoreactivity of β-tubulin showed increased expression among different grades of astrocytomas relative to controls and semiquantitatively increased nitration level in high-grade astrocytoma relative to control. Each nitroprotein was rationalized and related to the corresponding functional system to provide new insights into tyrosine nitration and its potential role in the

  4. Nucleolar and spindle associated protein 1 promotes the aggressiveness of astrocytoma by activating the Hedgehog signaling pathway

    OpenAIRE

    Wu, Xianqiu; Xu, Benke; Yang, Chao; Wang, Wentao; Zhong, Dequan; Zhao, Zhan; He, Longshuang; Hu, Yuanjun; JIANG, LILI; Li, Jun; Song, Libing; Zhang, Wei

    2017-01-01

    Background The prognosis of human astrocytoma is poor, and the molecular alterations underlying its pathogenesis still needed to be elucidated. Nucleolar and spindle associated protein 1 (NUSAP1) was observed in several types of cancers, but its role in astrocytoma remained unknown. Methods The expression of NUSAP1 in astrocytoma cell lines and tissues were measured with western blotting and Real-Time PCR. Two hundred and twenty-one astrocytoma tissue samples were analyzed by immunochemistry ...

  5. Association of Myelinated Retinal Nerve Fibers With Acquired Mulberry Retinal Astrocytoma: Coincidental or Relational?

    Science.gov (United States)

    Bypareddy, Ravi; Takkar, Brijesh; Lohchab, Monica; Azad, Shorya Vardhan; Chawla, Rohan

    2017-05-01

    Retinal astrocytoma is an important ocular finding for diagnosis of tuberous sclerosis complex and is also an association of neurofibromatosis. The authors present findings of a case of acquired astrocytoma associated with myelinated retinal nerve fibers. The authors also discuss the images and possible cause-effect relationship between them. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:441-442.]. Copyright 2017, SLACK Incorporated.

  6. The pilocytic astrocytoma : immunohistochemical and genetic studies in relation to tumor behavior

    NARCIS (Netherlands)

    Dirven, Clemens Maria Franciscus

    1998-01-01

    The tumors, studied in this thesis, were named "pilocytic astrocytomas" in the WHO classification of 1979, before that time they had been described under different names, such as gliocytoma embryonale and spongioblastoma. Pilocytic astrocytomas account for 6% of all brain tumors and occur mainly in

  7. Evaluation of miR-362 Expression in Astrocytoma of Human Brain Tumors

    Science.gov (United States)

    Kheirollahi, Majid; Moodi, Mahdiye; Ashouri, Saeideh; Nikpour, Parvaneh; Kazemi, Mohammad

    2017-01-01

    Background: Patients affected by gliomas have a poor prognosis. Astrocytoma is a subtype of glioma. Identification of biomarkers could be an effective way to an early diagnosis of tumor or to distinguish more aggressive tumors that need more intensive therapy. In this study, we investigated whether the expression of miR-362 was increased or decreased in patients with different grades of astrocytoma. Materials and Methods: miR-362 expression was compared in 25 patients with astrocytoma with that of 4 normal nonneoplastic brain tissues. Results: In all tumor tissues, the expression of miR-362 was significantly decreased relative to its expression in normal brain tissues. However, there was no significant difference between miR-362 expressions in high and low grades of astrocytoma. Conclusions: In conclusion, miR-362 showed a down-regulation pattern in astrocytoma tissues that was different from the pattern obtained from previously published microarray studies. PMID:29142892

  8. Spinal Cord Astrocytoma with Isocitrate Dehydrogenase 1 Gene Mutation.

    Science.gov (United States)

    Takai, Keisuke; Tanaka, Shota; Sota, Takashi; Mukasa, Akitake; Komori, Takashi; Taniguchi, Makoto

    2017-12-01

    In 2016, the World Health Organization updated its classification of tumors, adding genetic profiles to the conventional histopathologic typing. The authors present herein the first case of a 44-year-old female with isocitrate dehydrogenase-mutant World Health Organization grade II diffuse spinal astrocytoma diagnosed on the basis of both histopathologic and genetic findings. The present case underscores the significant role of a molecular genetic analysis in the differential diagnosis of intramedullary spinal gliomas. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Rab23 is overexpressed in human astrocytoma and promotes cell migration and invasion through regulation of Rac1.

    Science.gov (United States)

    Wang, Minghao; Dong, Qianze; Wang, Yunjie

    2016-08-01

    Rab23 overexpression has been implicated in several human cancers. However, its biological roles and molecular mechanism in astrocytoma have not been elucidated. The aim of this study is to explore clinical significance and biological roles of Rab23 in astrocytoma. We observed negative Rab23 staining in normal astrocytes and positive staining in 39 out of 86 (45 %) astrocytoma specimens using immunohistochemistry. The positive rate of Rab23 was higher in grades III and IV (56.5 %, 26/46) than grades I + II astrocytomas (32.5 %, 13/40, p astrocytoma by regulating cell invasion and migration through Rac1 activity.

  10. Intraoperative squash cytologic features of subependymal giant cell astrocytoma

    Directory of Open Access Journals (Sweden)

    Jitendra Nasit

    2016-01-01

    Full Text Available Subependymal giant cell astrocytoma (SEGA is a low grade (WHO Grade I tumor, usually seen in patients with tuberous sclerosis complex and commonly occurs at a lateral ventricular location. Intraoperative squash cytologic features can help in differentiating SEGA from gemistocytic astrocytoma (GA, giant cell glioblastoma and ependymoma, in proper clinical context and radiological findings, which may alter the surgical management. Here, we present a case of SEGA with squash cytologic findings and a review of cytology findings of SEGA presently available in the literature. Loose cohesive clusters of large polygonal cells containing an eccentric nucleus, evenly distributed granular chromatin, distinct to prominent nucleoli, and moderate to the abundant eosinophilic cytoplasm in a hair-like fibrillar background are the key cytologic features of SEGA. Other important features are moderate anisonucleosis and frequent binucleation and multinucleation. The absence of mitoses, necrosis, and vascular endothelial proliferation are important negative features. Other consistent features are cellular smears, few dispersed cells, few spindly strap-like cells, rare intranuclear cytoplasmic inclusion, and perivascular pseudorosettes.

  11. Intraoperative Squash Cytologic Features of Subependymal Giant Cell Astrocytoma.

    Science.gov (United States)

    Nasit, Jitendra; Vaghsiya, Viren; Hiryur, Srilaxmi; Patel, Smita

    2016-01-01

    Subependymal giant cell astrocytoma (SEGA) is a low grade (WHO Grade I) tumor, usually seen in patients with tuberous sclerosis complex and commonly occurs at a lateral ventricular location. Intraoperative squash cytologic features can help in differentiating SEGA from gemistocytic astrocytoma (GA), giant cell glioblastoma and ependymoma, in proper clinical context and radiological findings, which may alter the surgical management. Here, we present a case of SEGA with squash cytologic findings and a review of cytology findings of SEGA presently available in the literature. Loose cohesive clusters of large polygonal cells containing an eccentric nucleus, evenly distributed granular chromatin, distinct to prominent nucleoli, and moderate to the abundant eosinophilic cytoplasm in a hair-like fibrillar background are the key cytologic features of SEGA. Other important features are moderate anisonucleosis and frequent binucleation and multinucleation. The absence of mitoses, necrosis, and vascular endothelial proliferation are important negative features. Other consistent features are cellular smears, few dispersed cells, few spindly strap-like cells, rare intranuclear cytoplasmic inclusion, and perivascular pseudorosettes.

  12. A Novel Syndrome of Generalized Lipodystrophy Associated With Pilocytic Astrocytoma.

    Science.gov (United States)

    Patni, Nivedita; Alves, Crésio; von Schnurbein, Julia; Wabitsch, Martin; Tannin, Grace; Rakheja, Dinesh; Garg, Abhimanyu

    2015-10-01

    A rare presentation of hypothalamic tumors in infants and young children is profound emaciation and generalized loss of sc adipose tissue, also known as "diencephalic syndrome." Similar loss of sc fat can be observed in children with acquired generalized lipodystrophy or congenital generalized lipodystrophy. Precise diagnosis may be challenging early in the course of the disease, especially in the absence of metabolic abnormalities. We report three males who presented with poor weight gain and generalized loss of sc fat at birth to 3 years of age consistent with generalized lipodystrophy, with subsequent development of pilocytic astrocytoma. Two of them had hypothalamic tumors, and one had a multicentric tumor with a large right parietal mass. Our patients are unique because the onset of lipodystrophy occurred 2.5 to 7.3 years before the diagnosis of brain tumor, and all of them gained body fat or weight after surgical removal and/or chemotherapy. One patient had hepatosplenomegaly and impaired glucose tolerance, and another patient had severe hyperglycemia and hypertriglyceridemia during the course of the disease. Two patients presented with central precocious puberty and advanced bone age at the chronological age of 6 years. It is likely that pilocytic astrocytoma may induce generalized lipodystrophy by paraneoplastic antiadipocyte antibody formation or by excessive hormones or cytokine secretion resulting in excess lipolysis from adipocytes. We conclude that young children presenting with idiopathic acquired generalized lipodystrophy or atypical congenital generalized lipodystrophy, with or without metabolic abnormalities, should prompt investigation for brain tumors.

  13. GFAPδ/GFAPα ratio directs astrocytoma gene expression towards a more malignant profile

    Science.gov (United States)

    Giuliani, Fabrizio; Moeton, Martina; Kanski, Regina; Sluijs, Jacqueline A.; van Strien, Miriam E.; Kamphuis, Willem; Robe, Pierre A.J.; Hol, Elly M.

    2017-01-01

    Astrocytomas are the most common malignant brain tumours and are to date incurable. It is unclear how astrocytomas progress into higher malignant grades. The intermediate filament cytoskeleton is emerging as an important regulator of malignancy in several tumours. The majority of the astrocytomas express the intermediate filament protein Glial Fibrillary Acidic Protein (GFAP). Several GFAP splice variants have been identified and the main variants expressed in human astrocytoma are the GFAPα and GFAPδ isoforms. Here we show a significant downregulation of GFAPα in grade IV astrocytoma compared to grade II and III, resulting in an increased GFAPδ/α ratio. Mimicking this increase in GFAPδ/α ratio in astrocytoma cell lines and comparing the subsequent transcriptomic changes with the changes in the patient tumours, we have identified a set of GFAPδ/α ratio-regulated high-malignant and low-malignant genes. These genes are involved in cell proliferation and protein phosphorylation, and their expression correlated with patient survival. We additionally show that changing the ratio of GFAPδ/α, by targeting GFAP expression, affected expression of high-malignant genes. Our data imply that regulating GFAP expression and splicing are novel therapeutic targets that need to be considered as a treatment for astrocytoma. PMID:29152145

  14. Knockdown of STAT3 expression by RNAi induces apoptosis in astrocytoma cells

    Directory of Open Access Journals (Sweden)

    Kruger Mathew M

    2003-09-01

    Full Text Available Abstract Background Astrocytomas are the most common type of primary central nervous system tumors. They are frequently associated with genetic mutations that deregulate cell cycle and render these tumors resistant to apoptosis. STAT3, signal transducer and activator of transcription 3, participates in several human cancers by inducing cell proliferation and inhibiting apoptosis and is frequently activated in astrocytomas. Methods RNA interference was used to knockdown STAT3 expression in human astrocytes and astrocytoma cell lines. The effect of STAT3 knockdown on apoptosis, cell proliferation, and gene expression was then assessed by standard methods. Results We have found that STAT3 is constitutively activated in several human astrocytoma cell lines. Knockdown of STAT3 expression by siRNA induces morphologic and biochemical changes consistent with apoptosis in several astrocytoma cell lines, but not in primary human astrocytes. Moreover, STAT3 is required for the expression of the antiapoptotic genes survivin and Bcl-xL in the A172 glioblastoma cell line. Conclusion These results show that STAT3 is required for the survival of some astrocytomas. These studies suggest STAT3 siRNA could be a useful therapeutic agent for the treatment of astrocytomas.

  15. Subependymal giant cell astrocytoma (SEGA): a case report and review of the literature.

    Science.gov (United States)

    Tahiri Elousrouti, Layla; Lamchahab, Meryem; Bougtoub, Nawal; Elfatemi, Hinde; Chbani, Laila; Harmouch, Taoufik; Maaroufi, Mustapha; Amarti Riffi, Afaf

    2016-02-09

    Subependymal giant cell astrocytoma is a rare tumor that occurs in the wall of the lateral ventricle and foramen of Monro and, rarely, in the third ventricle. It is one of the intracranial lesions found in tuberous sclerosis complex (which include subependymal nodules, cortical tubers, retinal astrocytoma and subependymal giant cell astrocytoma), but cases without such lesions have also been reported in the literature. It was described for the first time in 1908 by Vogt as part of the typical triad of tuberous sclerosis complex. At the 2012 Washington Consensus Conference, it was decided by the invited expert panel to document the definition of subependymal giant cell astrocytoma as a lesion at the caudothalamic groove with either a size of more than 1 cm in any direction or a subependymal lesion at any location that has shown serial growth on consecutive imaging regardless of size. Most subependymal giant cell astrocytomas will show avid enhancement after contrast administration; however, a growing subependymal lesion even in the absence of enhancement should be considered a subependymal giant cell astrocytoma. We report a case of subependymal giant cell astrocytoma in a 10-year-old white girl, who had no clinical symptoms of tuberous sclerosis. A computed tomography scan revealed a voluminous mass in her perilateral ventricle. An extemporaneous examination was in favor of a benign ganglioglioma tumor. After fixation in 10 % neutral-buffered formalin, embedding in paraffin and staining with hematoxylin, eosin and safran, the definitive diagnosis was subependymal giant cell astrocytoma. Subependymal giant cell astrocytoma is a rare tumor of the central nervous system whose diagnosis is based on clinical, radiological, histological and immunohistochemical arguments. For its rarity, we must consider this diagnosis when faced with a mass near the foramen of Monro in the pediatric population even if there are no other features of tuberous sclerosis complex.

  16. Nucleolar and spindle associated protein 1 promotes the aggressiveness of astrocytoma by activating the Hedgehog signaling pathway.

    Science.gov (United States)

    Wu, Xianqiu; Xu, Benke; Yang, Chao; Wang, Wentao; Zhong, Dequan; Zhao, Zhan; He, Longshuang; Hu, Yuanjun; Jiang, Lili; Li, Jun; Song, Libing; Zhang, Wei

    2017-09-12

    The prognosis of human astrocytoma is poor, and the molecular alterations underlying its pathogenesis still needed to be elucidated. Nucleolar and spindle associated protein 1 (NUSAP1) was observed in several types of cancers, but its role in astrocytoma remained unknown. The expression of NUSAP1 in astrocytoma cell lines and tissues were measured with western blotting and Real-Time PCR. Two hundred and twenty-one astrocytoma tissue samples were analyzed by immunochemistry to demonstrate the correlation between the NUSAP1 expression and clinicopathological characteristics. 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) assay, colony formation, transwell matrix penetration assay, wound healing assay and anchorage-independent growth assay were used to investigate the biological effect of NUSAP1 in astrocytoma. An intracranial brain xenograft tumor model was used to confirm the oncogenic role of NUSAP1 in human astrocytoma. Luciferase reporter assay was used to investigate the effect of NUSAP1 on Hedgehog signaling pathway. NUSAP1 was markedly overexpressed in astrocytoma cell lines and tissues compared with normal astrocytes and brain tissues. NUSAP1 was found to be overexpressed in 152 of 221 (68.78%) astrocytoma tissues, and was significantly correlated to poor survival. Further, ectopic expression or knockdown of NUSAP1 significantly promoted or inhibited, respectively, the invasive ability of astrocytoma cells. Moreover, intracranial xenografts of astrocytoma cells engineered to express NUSAP1 were highly invasive compared with the parental cells. With regard to its molecular mechanism, upregulation of NUSAP1 in astrocytoma cells promoted the nuclear translocation of GLI family zinc finger 1 (GLI1) and upregulated the downstream genes of the Hedgehog pathway. These findings indicate that NUSAP1 contributes to the progression of astrocytoma by enhancing tumor cell invasiveness via activation of the Hedgehog signaling pathway, and that NUSAP1

  17. CD133 identifies perivascular niches in grade II-IV astrocytomas

    DEFF Research Database (Denmark)

    Christensen, Karina; Schrøder, Henrik; Kristensen, Bjarne

    2008-01-01

    The aim of the present study was to investigate the localization and distribution of the putative brain tumour stem cell marker CD133 in formalin fixed paraffin embedded astrocytomas. A retrospective analysis of 114 grade II, III and IV astrocytomas was undertaken. The immunohistochemical...... volume fraction of CD133(+) niches and all CD133(+) tumour cells and tumour grade. However, the volume fraction of CD133(+) blood vessels increased significantly from 0.4% in diffuse astrocytomas to 2.2% in glioblastomas. Neither of them was related to patient survival. Double immunofluorescence...... stainings showed that the CD133(+) niches both contained CD133(+) cells with and without co-expression of the intermediate filament protein marker nestin, and only few CD133(+)/MIB-1(+) proliferating cells were found. In conclusion, a CD133(+) perivascular stem cell-like entity exists in astrocytomas. CD133...

  18. Expression and prognostic impact of matrix metalloproteinase-2 (MMP-2) in astrocytomas

    DEFF Research Database (Denmark)

    Ramachandran, Rahimsan K.; Sørensen, Mia D.; Aaberg-Jessen, Charlotte

    2017-01-01

    of this tumor. Matrix metalloproteinase-2 (MMP-2) is an extracellular matrix degrading enzyme which has been shown to play important roles in different cancers. The aim of this study was to investigate the expression and prognostic potential of MMP-2 in astrocytomas. Tissue samples from 89 patients diagnosed...... with diffuse astrocytoma, anaplastic astrocytoma and glioblastoma were stained immunohistochemically using a monoclonal MMP-2 antibody. The MMP-2 intensity in cytoplasm/membrane was quantified by a trained software-based classifier using systematic random sampling in 10% of the tumor area. We found MMP-2......Astrocytomas are the most frequent primary brain tumors in adults, and despite aggressive treatment patients often experience recurrence. Survival decreases with increasing tumor grade, and especially patients with grade IV glioblastoma have poor prognosis due to the aggressive character...

  19. Recurrent somatic alterations of FGFR1 and NTRK2 in pilocytic astrocytoma

    NARCIS (Netherlands)

    Jones, David T. W.; Hutter, Barbara; Jäger, Natalie; Korshunov, Andrey; Kool, Marcel; Warnatz, Hans-Jörg; Zichner, Thomas; Lambert, Sally R.; Ryzhova, Marina; Quang, Dong Anh Khuong; Fontebasso, Adam M.; Stütz, Adrian M.; Hutter, Sonja; Zuckermann, Marc; Sturm, Dominik; Gronych, Jan; Lasitschka, Bärbel; Schmidt, Sabine; Seker-Cin, Huriye; Witt, Hendrik; Sultan, Marc; Ralser, Meryem; Northcott, Paul A.; Hovestadt, Volker; Bender, Sebastian; Pfaff, Elke; Stark, Sebastian; Faury, Damien; Schwartzentruber, Jeremy; Majewski, Jacek; Weber, Ursula D.; Zapatka, Marc; Raeder, Benjamin; Schlesner, Matthias; Worth, Catherine L.; Bartholomae, Cynthia C.; von Kalle, Christof; Imbusch, Charles D.; Radomski, Sylwester; Lawerenz, Chris; van Sluis, Peter; Koster, Jan; Volckmann, Richard; Versteeg, Rogier; Lehrach, Hans; Monoranu, Camelia; Winkler, Beate; Unterberg, Andreas; Herold-Mende, Christel; Milde, Till; Kulozik, Andreas E.; Ebinger, Martin; Schuhmann, Martin U.; Cho, Yoon-Jae; Pomeroy, Scott L.; von Deimling, Andreas; Witt, Olaf; Taylor, Michael D.; Wolf, Stephan; Karajannis, Matthias A.; Eberhart, Charles G.; Scheurlen, Wolfram; Hasselblatt, Martin; Ligon, Keith L.; Kieran, Mark W.; Korbel, Jan O.; Yaspo, Marie-Laure; Brors, Benedikt; Felsberg, Jörg; Reifenberger, Guido; Collins, V. Peter; Jabado, Nada; Eils, Roland; Lichter, Peter; Pfister, Stefan M.

    2013-01-01

    Pilocytic astrocytoma, the most common childhood brain tumor, is typically associated with mitogen-activated protein kinase (MAPK) pathway alterations. Surgically inaccessible midline tumors are therapeutically challenging, showing sustained tendency for progression and often becoming a chronic

  20. Overexpression of Fli-1 in astrocytoma is associated with poor prognosis

    OpenAIRE

    Tsai, Hung-Pei; Tsai, Tai-Hsin; Hsieh, Ya-Ju; Chen, Yi-Ting; Lee, Chih-Ling; Tsai, Yi-Cheng; She, Ting-Chang; Lin, Chih-Lung; Chai, Chee-Yin; Kwan, Aij-Lie

    2017-01-01

    Background Astrocytoma, a common and highly malignant type of brain tumor, is associated with poor overall survival despite advances in surgical treatment, radiotherapy, and chemotherapy. The nuclear transcription factor Fli-1 has been shown to increase cellular proliferation and tumorigenesis in many types of cancer; however, previous reports have not described a correlation between clinical outcomes and Fli-1 in astrocytoma patients. The present study aimed to elucidate the clinical role of...

  1. miR-137 acts as a tumor suppressor in astrocytoma by targeting RASGRF1.

    Science.gov (United States)

    Deng, Danni; Xue, Lian; Shao, Naiyuan; Qu, Hongtao; Wang, Qiang; Wang, Suinuan; Xia, Xiwei; Yang, Yilin; Zhi, Feng

    2016-03-01

    Astrocytoma is one of the most common primary central nervous system tumors and has both high mortality and a poor 5-year survival rate. MicroRNAs (miRNAs) play important roles in carcinogenesis by acting on multiple signaling pathways. Although we have demonstrated that miR-137 is downregulated in astrocytoma tissues, the role of miR-137 in astrocytoma still remains unknown. In the present study, we aimed to investigate the function of miR-137 and its possible target genes in astrocytoma. miR-137 was significantly downregulated in astrocytoma tissues, and its expression level was inversely correlated with the clinical stage. Restoring miR-137 was able to dramatically inhibit cell proliferation, migration, and invasion and enhance apoptosis in vitro, whereas silencing its expression inhibited these processes. By overexpressing or inhibiting miR-137 in cancer cells, we experimentally confirmed that miR-137 directly recognized the 3'-UTR (3'-untranslated region) of the RASGRF1 (Ras protein-specific guanine nucleotide-releasing factor 1) transcript and regulated RASGRF1 expression. Furthermore, an inverse correlation was observed between miR-137 levels and RASGRF1 protein levels, but not mRNA levels, in astrocytoma samples. The silencing of RASGRF1 resulted in similar effects to miR-137 restoration in cancer cells. Finally, overexpression of RASGRF1 rescued the inhibitory effects of miR-137. Taken together, our results indicate that miR-137 acts as a tumor suppressor in astrocytoma by targeting RASGRF1. These findings suggest that miR-137 may serve as a novel therapeutic target in astrocytoma treatment.

  2. Adult Pilomyxoid Astrocytoma Mimicking a Cortical Brain Tumor: MR Imaging Findings

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    Jang, Jong Chang; Weon, Young Cheol; Suh, Jae Hee; Kim, Young; Hwang, Jae Cheol [Ulsan University Hospital, Ulsan (Korea, Republic of)

    2010-08-15

    A pilomyxoid astrocytoma (PMA) is a recently identified low-grade neoplasm that was previously classified as a pilocytic astrocytoma (PA), yet demonstrates unique histological features and more aggressive behavior. Although a PMA is generally a tumor of early childhood and typically occurs in the hypothalamic/chiasmatic region, it can mimic cortical tumors, especially in adults. We report the MR findings of a PMA presenting as a cortical brain tumor in an adult with neurofibromatosis 1 (NF1)

  3. Prevention against diffuse spinal cord astrocytoma: can the Notch pathway be a novel treatment target?

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    Jian-jun Sun

    2015-01-01

    Full Text Available This study was designed to investigate whether the Notch pathway is involved in the development of diffuse spinal cord astrocytomas. BALB/c nude mice received injections of CD133 + and CD133− cell suspensions prepared using human recurrent diffuse spinal cord astrocytoma tissue through administration into the right parietal lobe. After 7-11 weeks, magnetic resonance imaging was performed weekly. Xenografts were observed on the surfaces of the brains of mice receiving the CD133 + cell suspension, and Notch-immunopositive expression was observed in the xenografts. By contrast, no xenografts appeared in the identical position on the surfaces of the brains of mice receiving the CD133− cell suspension, and Notch-immunopositive expression was hardly detected either. Hematoxylin-eosin staining and immunohistochemical staining revealed xenografts on the convex surfaces of the brains of mice that underwent CD133 + astrocytoma transplantation. Some sporadic astroglioma cells showed pseudopodium-like structures, which extended into the cerebral white matter. However, it should be emphasized that the subcortex xenograft with Notch-immunopositive expression was found in the fourth mouse received injection of CD133− astrocytoma cells. However, these findings suggest that the Notch pathway plays an important role in the formation of astrocytomas, and can be considered a novel treatment target for diffuse spinal cord astrocytoma.

  4. The relationship between polymorphisms of XRCC5 genes with astrocytoma prognosis in the Han Chinese population

    Science.gov (United States)

    Li, Lei; Zhang, Jiayi; Wu, Ruipeng; Zhang, Yuan; Kang, Longli; Yuan, Dongya; Jin, Tianbo

    2016-01-01

    Background Gliomas are highly malignant with a poor prognosis. Studies have reported that DNA repair genes influence risk for glioma, but its relationship with prognosis is unclear. In this study, we want to explore the relationship between DNA repair genes (XRCC3, XRCC4 and XRCC5) and prognosis of astrocytoma in the Chinese Han population. Materials and Methods 160 astrocytoma cases were recruited in our study. Survival probabilities were estimated by using Kaplan–Meier analysis, and significant differences were analyzed by using the log-rank test. Cox proportional hazards models were used to analyze the associations between genotypes with astrocytoma survival. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using multivariable models. All tests were two-sided and p astrocytoma prognosis. Further, the “A/A” genotype of rs9288516 in XRCC5 (HR: 1.67, 95%CI: 1.02 - 2.72, p = 0.042) had significantly outcomes after adjusting for potential confounders, patients with poor tumor differentiation and the coexistence of the unfavorable genotypes. Conclusion These results suggest that polymorphisms of XRCC5 play an important role in astrocytoma prognosis in the Chinese Han population which could be used in the determination of astrocytoma prognosis in clinical researches. PMID:27852033

  5. Biochemical Signatures of Doppel Protein in Human Astrocytomas to Support Prediction in Tumor Malignancy

    Directory of Open Access Journals (Sweden)

    Paola Rognoni

    2010-01-01

    Full Text Available Doppel (Dpl is a membrane-bound glycoprotein mainly expressed in the testis of adult healthy people. It is generally absent in the central nervous system, but its coding gene sequence is ectopically expressed in astrocytoma specimens and in derived cell lines. In this paper, we investigated the expression and the biochemical features of Dpl in a panel of 49 astrocytoma specimens of different WHO malignancy grades. As a result, Dpl was expressed in the majority of the investigated specimens (86%, also including low grade samples. Importantly, Dpl exhibited different cellular localizations and altered glycan moieties composition, depending on the tumor grade. Most low-grade astrocytomas (83% showed a membrane-bound Dpl, like human healthy testis tissue, whereas the majority of high-grade astrocytomas (75% displayed a cytosolic Dpl. Deglycosylation studies with N-glycosidase F and/or neuraminidase highlighted defective glycan moieties and an unexpected loss of sialic acid. To find associations between glial tumor progression and Dpl biochemical features, predictive bioinformatics approaches were produced. In particular, Decision tree and Nomogram analysis showed well-defined Dpl-based criteria that separately clustered low-and high-grade astrocytomas. Taken together, these findings show that in astrocytomas, Dpl undergoes different molecular processes that might constitute additional helpful tools to characterize the glial tumor progression.

  6. [Clinical effects of microsurgery in spinal cord anaplastic astrocytoma].

    Science.gov (United States)

    Zhang, L; Jia, W Q; Kong, D S; Zhang, Z F; Yang, J

    2017-06-01

    Objective: To investigate the surgical outcomes and prognosis of spinal cord anaplastic astrocytoma (AA). Methods: A total of 27 consecutive patients diagnosed as spinal cord AA between January 2008 and May 2015 in Department of Neurosurgery of Beijing Tiantan Hospital were retrospectively reviewed. There were 18 males and 9 females, the mean age was (30.7±13.0) years (ranging from 5 to 52 years). The lesions were located at cervical level in 8 patients, at thoracic level in 9 patients, at cervicothoracic level in 3 patients, and at thoracolumbar level in 7 patients, the average number of vertebral was 3.3±1.3.The median time from onset of symptom to surgery was 4 months, ranging from 3 days to 48 months. The clinical presentations were weakness (23 cases), paresthesia (22 cases), pain (20 cases), sphincter disorder (15 cases) and paralysis (7 cases). The preoperative modified McCormick scale was as follows: grade Ⅱ for 6 cases, grade Ⅲ for 7 cases, grade Ⅳ for 7 cases, grade Ⅴ for 7 cases. The tumors were surgically removed via posterior median approach with the monitoring of the somatosensory-evoked potentials to minimize the neurological injury. All of the patients were recommonded to receive adjuvant chemotherapy and radiotherapy postoperatively after pothological verified and followed up by clinic interview or telephone postoperatively. Log-rank test was used to calculate the survival rate. Results: Gross total resection and subtotal resection were achieved in 18 patients and partial resection in 9. Twenty patients received adjuvant chemotherapy and (or) radiotherapy, 7 patients did not received chemoradiation postoperatively. Nineteen patients died and 8 were alive at the last follow-up. The median survival time was 23 months with 1 and 2-year survival rates of 85.2% and 50.0%.There was no statistical significance between subtotal resection group and partial resection group(χ(2)=0.089, P=0.880), the survival rates of patients in chemotherapy group

  7. WHO grade-specific comparative genomic hybridization pattern of astrocytoma - a meta-analysis.

    Science.gov (United States)

    Holland, Heidrun; Koschny, Thomas; Ahnert, Peter; Meixensberger, Jürgen; Koschny, Ronald

    2010-10-15

    To detect novel genetic alterations, many astrocytomas have been investigated by comparative genomic hybridization (CGH). To identify aberration profiles characteristic of World Health Organization (WHO) grade I, II, III, and IV astrocytoma, we performed a meta-analysis of detailed genome wide CGH data of all 467 cases published so far. After expansion of all given aberrations to the maximum of 850 GTG-band resolution, the frequencies of genetic imbalances were calculated for each chromosomal band, separately for all four WHO grades. Low-grade astrocytoma has already demonstrated one characteristic of glioblastoma multiforme, gain of chromosome 7 with a hot spot at 7q32, but without loss of chromosome 10. In anaplastic astrocytoma, a more complex aberration pattern emerges from diffuse genetic imbalances. Gains of 7q32-q36 and 7p12 become the most frequent aberrations at chromosome 7. In glioblastoma multiforme, coarse aberrations like +7, -9p, -10, and -13 represent the most frequent aberrations as a characteristic pattern. In contrast to lower tumor grades, glioblastoma multiforme demonstrates +7p12 as the most frequently affected band on chromosome 7. To quantify the gradual transition from WHO grade II-IV astrocytoma, we calculated the relative increase and decrease in frequency for each detected aberration of the tumor genome. The most pronounced and diverse changes of genetic material occur at the virtual transition from low-grade to anaplastic astrocytoma. Further transition to glioblastoma multiforme is characterized by gain of 1p, chromosome 7, and loss of chromosome 10. Summing up, the expansion of the CGH results to the 850 GTG-band resolution enabled a meta-analysis to visualize WHO grade-specific aberration profiles in astrocytoma. Copyright © 2010 Elsevier GmbH. All rights reserved.

  8. Aspecific inflammatory lesion (histiocytosis?) simulating intramedullary astrocytoma. Case report.

    Science.gov (United States)

    Palma, L; Rizzo, G; Lio, R; Mariottini, A; Mazzocchio, R

    1999-03-01

    We report an exceptional case of aspecific inflammatory lesion of the thoracic spinal cord simulating an intramedullary glial tumor. Patient history was characterized by progressive spastic paraparesis with urinary incontinence; MR imaging (T4-T5) showed an enhancing intrinsic mass lesion. Myelotomy enabled partial resection of grayish astrocytoma-like tissue. Only light microscope examination was possible and disclosed aspecific inflammatory tissue composed of eosinophils, lymphocytes and histiocytes. After the operation, the patient improved promptly and no further therapy was administered. Control MRI after four months, one year and two years showed complete disappearance of the intramedullary mass lesion and the patient remained clinically stable with no other signs of disease. Since electron microscopic as well as immunohistochemical studies were not available, a definitive histological diagnosis was not possible. However on the basis of some clinical similarities with cases of isolated histiocytosis X of the CNS reported in the literature, we suggest that a diagnosis of isolated intramedullary eosinophilic granuloma could be reasonable.

  9. PHAKOMATOSIS : INTRESTING CASES OF TUBEROUS SCLEROSIS WITH RETINAL ASTROCYTOMA

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    Srinivasa Rao

    2015-05-01

    Full Text Available NTRODUCTION: Tuberous sclerosis complex (TSC or Morbus Bourneville - Pringle disease is an autosomal dominant phakomatosis, first described by Desiree - Magloire Bourneville in 1880. Tuberous sclerosis is a genetic disorder characterized by the growth of numerous benign tumours in many parts of the body caused by mutations on either of two genes, TSC1 and TSC2. This rare genetic disorder is usually associated with a triad of seizures, mental retardation and cutaneous lesions. Approximately one half of all patients affected by TS develop at least one retinal astrocytoma in one eye. PRESENTATION OF CASES: In the department of ophthalmology, G.S.L M edical C ollege, Rajahmundry, we came across 3 cases of tuberous sclerosis involving multi organ systems. Out of 3 cases, 2 cases were reported to be familial and 1case is sporadic, with a history of epilepsy with angiofibromatosis lesions over the face, multiple ash - leaf lesions over the abdomen, renal angiomyolipomas, multiple subependymal nodules in brain and retinal astrocytic hamartomas in the retina. CONCLUSION: It is important to be cognizant of the likely presence of systemic and ocular pathology in a child with mental retardation and skin lesions. Identification of retinal phakomatosis during ocular evaluation in any suspected case of Tuberous sclerosis can aid in the establishment of the diagnosis of the disease

  10. Diagnostic value of susceptibility-weighted imaging in grading diffusely infiltrating astrocytomas

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    SHEN Jun-lin

    2012-12-01

    Full Text Available Objective To investigate the diagnostic value of susceptibility-weighted imaging (SWI in grading diffusely infiltrating astrocytomas. Methods Forty-three patients with pathologically proven diffusely infiltrating astrocytomas were collected, and underwent preoperative MRI conventional sequences (including axial T1WI, T2WI and FLAIR and axial SWI. The ability of showing intratumoral small vessels and hemorrhagic focuses were compared between SWI and conventional techniques. The signal intensities, distribution of venules and bleeding incidence of the tumors were observed respectively on SWI, and the numbers of intratumoral small vessels and cerebral microbleeds, and the sectional areas of bleedings were compared within the three grades of astrocytomas. Results There were significant differences between SWI and conventional sequences in displaying numbers of small vessels and microbleeds and sizes of bleedings (P < 0.01, for all. Low-grade astrocytomas (WHO Ⅱ displayed mainly as hyperintense, while high-grade (WHO Ⅲ, Ⅳ ones showed mainly equisignal or low intensities; venules inside low-grade astrocytomas were sparse, but abundant inside high-grade ones; the incidence of hemorrhage in low-grade astrocytomas was less frequent than that in high-grade ones. The numbers of venules in three groups were 3.77 ± 1.11, 11.86 ± 1.22 and 20.00 ± 1.32, respectively. The numbers of cerebral microbleeds were 0.47 ± 0.39, 3.32 ± 0.42 and 4.38 ± 0.46, respectively. The sectional areas of bleedings were (0.78 ± 1.31 cm2, (3.05 ± 4.40 cm2 and (4.23 ± 4.55 cm2, respectively. The differences among the three groups were all statistically significant (P < 0.01, for all. Conclusion SWI was more sensitive than conventional techniques in showing small vessels and bleeding sites in astrocytomas. The signal intensities, distribution of venules and bleeding incidence of tumors were significantly different between low-grade and high-grade astrocytomas. The

  11. Expression patterns of Wnt signaling component, secreted frizzled‑related protein 3 in astrocytoma and glioblastoma.

    Science.gov (United States)

    Pećina-Šlaus, Nives; Kafka, Anja; Varošanec, Ana Maria; Marković, Leon; Krsnik, Željka; Njirić, Niko; Mrak, Goran

    2016-05-01

    Secreted frizzled-related protein 3 (SFRP3) is a member of the family of soluble proteins, which modulate the Wnt signaling cascade. Novel research has identified aberrant expression of SFRPs in different types of cancer. In the present study the expression intensities and localizations of the SFRP3 protein across different histopathological grades of astrocytic brain tumors were investigated by immunohistochemistry, digital scanning and image analysis. The results demonstrated that the differences between expression levels and malignancy grades were statistically significant. Tumors were classified into four malignancy grades according to the World Health Organization guidelines. Moderate (P=0.014) and strong (P=0.028) nuclear expression levels were significantly different in pilocytic (grade I) and diffuse (grade II) astrocytomas demonstrating higher expression values, as compared with anaplastic astrocytoma (grade III) and glioblastoma (grade IV). When the sample was divided into two groups, the moderate and high cytoplasmic expression levels were observed to be significantly higher in glioblastomas than in the group comprising astrocytoma II and III. Furthermore, the results indicated that high grade tumors were associated with lower values of moderate (P=0.002) and strong (P=0.018) nuclear expression in comparison to low grade tumors. Analysis of cytoplasmic staining demonstrated that strong cytoplasmic expression was significantly higher in the astrocytoma III and IV group than in the astrocytoma I and II group (P=0.048). Furthermore, lower grade astrocytomas exhibited reduced membranous SFRP3 staining when compared with higher grade astrocytomas and this difference was statistically significant (P=0.036). The present results demonstrated that SFRP3 protein expression levels were decreased in the nucleus in higher grade astrocytoma (indicating the expected behavior of an antagonist of Wnt signaling), whereas when the SFRP3 was located in the

  12. Expression patterns of Wnt signaling component, secreted frizzled-related protein 3 in astrocytoma and glioblastoma

    Science.gov (United States)

    PEĆINA-ŠLAUS, NIVES; KAFKA, ANJA; VAROŠANEC, ANA MARIA; MARKOVIĆ, LEON; KRSNIK, ŽELJKA; NJIRIĆ, NIKO; MRAK, GORAN

    2016-01-01

    Secreted frizzled-related protein 3 (SFRP3) is a member of the family of soluble proteins, which modulate the Wnt signaling cascade. Novel research has identified aberrant expression of SFRPs in different types of cancer. In the present study the expression intensities and localizations of the SFRP3 protein across different histopathological grades of astrocytic brain tumors were investigated by immunohistochemistry, digital scanning and image analysis. The results demonstrated that the differences between expression levels and malignancy grades were statistically significant. Tumors were classified into four malignancy grades according to the World Health Organization guidelines. Moderate (P=0.014) and strong (P=0.028) nuclear expression levels were significantly different in pilocytic (grade I) and diffuse (grade II) astrocytomas demonstrating higher expression values, as compared with anaplastic astrocytoma (grade III) and glioblastoma (grade IV). When the sample was divided into two groups, the moderate and high cytoplasmic expression levels were observed to be significantly higher in glioblastomas than in the group comprising astrocytoma II and III. Furthermore, the results indicated that high grade tumors were associated with lower values of moderate (P=0.002) and strong (P=0.018) nuclear expression in comparison to low grade tumors. Analysis of cytoplasmic staining demonstrated that strong cytoplasmic expression was significantly higher in the astrocytoma III and IV group than in the astrocytoma I and II group (P=0.048). Furthermore, lower grade astrocytomas exhibited reduced membranous SFRP3 staining when compared with higher grade astrocytomas and this difference was statistically significant (P=0.036). The present results demonstrated that SFRP3 protein expression levels were decreased in the nucleus in higher grade astrocytoma (indicating the expected behavior of an antagonist of Wnt signaling), whereas when the SFRP3 was located in the cytoplasm an

  13. Epigenetic Silencing of the Protocadherin Family Member PCDH-γ-All in Astrocytomas

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    Anke Waha

    2005-03-01

    Full Text Available In a microarray-based methylation analysis of astrocytomas [World Health Organization (WHO grade II], we identified a CpG island within the first exon of the protocadherin-γ subfamily A11 (PCDH-γ-A11 gene that showed hypermethylation compared to normal brain tissue. Bisulfite sequencing and combined bisulfite restriction analysis (COBRA was performed to screen low- and high-grade astrocytomas for the methylation status of this CpG island. Hypermethylation was detected in 30 of 34 (88% astrocytomas (WHO grades II and III, 20 of 23 (87% glioblastomas (WHO grade IV, 8 of 8 (100% glioma cell lines. There was a highly significant correlation (P = .00028 between PCDH-γ-A11 hypermethylation and decreased transcription as determined by competitive reverse transcription polymerase chain reaction in WHO grades II and III astrocytomas. After treatment of glioma cell lines with a demethylating agent, transcription of PCDH-γ-A11 was restored. In summary, we have identified PCDH-γ-A11 as a new target silenced epigenetically in astrocytic gliomas. The inactivation of this cell-cell contact molecule might be involved in the invasive growth of astrocytoma cells into normal brain parenchyma.

  14. Correlation of Altered Expression of the Autophagy Marker LC3B with Poor Prognosis in Astrocytoma

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    Daniel Winardi

    2014-01-01

    Full Text Available Glioblastoma multiforme is one of the most serious malignant brain tumors and is characterized by resistance to chemotherapy and radiation therapy. Recent studies suggest that autophagy may play an important role not only in the regulation of cancer development and progression but also in determining the response of cancer cells to anticancer therapy. The purpose of the present study was to assess the relationship between protein expressions of two autophagy markers, LC3B and Beclin-1, with clinical parameters in astrocytoma patients. Furthermore, the expression of CD133, a marker of the cancer stem-like cells, in astrocytoma patients was also investigated. A total of 106 thin-section slides were retrospectively collected from astrocytoma patients. LC3B, but not Beclin-1, protein expression was found to significantly correlate with resistance to radiation- or chemotherapy. In addition, high intensity of LC3B staining was predictive of poor prognosis. Furthermore, survival time of patients with high-level expression in both CD133 and LC3B was significantly shorter than those with weak expression in both CD133 and LC3B. These results suggest that astrocytoma cancer stem-like cells together with enhanced autophagy may cause resistance to radiation therapy/chemotherapy and that targeting the cancer stem-like cell in astrocytoma may offer a viable therapeutic approach.

  15. Three meta-analyses define a set of commonly overexpressed genes from microarray datasets on astrocytomas.

    Science.gov (United States)

    Liu, Zhongyu; Xie, Mengyu; Yao, Zhiqiang; Niu, Yulong; Bu, Youquan; Gao, Chunfang

    2013-02-01

    Glioma is one of the most common tumors of the central nervous system, and one of its main types is astrocytoma. Microarray technology has been widely used to explore the molecular mechanism of cancer. It is universally accepted that meta-analysis considerably improves the statistical robustness of results, particularly in clinical research. To obtain the maximum reliability, we used three different meta-analyses to integrate the four microarray datasets, GSE16011, GSE4290, GSE2223, and GSE19728 (local), and defined the common differentially expressed genes (DEGs) in astrocytomas compared with normal brain tissue. Four DEGs, PCNA, CDC2, CDK2 and CCNB2, which are components of the cell cycle pathway, were chosen for Real-Time Polymerase Chain Reaction (RT-PCR) and immunohistochemistry validation. PCNA is similar to the P53 gene and has been widely implicated in various cancers including gliomas. Therefore, the expression status of PCNA in our study was considered as a reference to test our whole experimental scheme, and the results indicate that our methodology is valid. Although a few studies have reported the overexpression of the CDC2, CDK2 and CCNB2 genes in glioma cell lines, we are the first to identify the statuses of these genes in human astrocytoma tissues at the mRNA and protein levels. The results of the gene validations strongly suggested that the genes play an important role in astrocytomas and could potentially be valuable in the diagnosis and treatment of astrocytoma.

  16. Expression of estrogen and progesterone receptors in astrocytomas: a literature review

    Directory of Open Access Journals (Sweden)

    Cléciton Braga Tavares

    Full Text Available Gliomas are the most common type of primary central nervous system neoplasm. Astrocytomas are the most prevalent type of glioma and these tumors may be influenced by sex steroid hormones. A literature review for the presence of estrogen and progesterone receptors in astrocytomas was conducted in the PubMed database using the following MeSH terms: “estrogen receptor beta” OR “estrogen receptor alpha” OR “estrogen receptor antagonists” OR “progesterone receptors” OR “astrocytoma” OR “glioma” OR “glioblastoma”. Among the 111 articles identified, 13 studies met our inclusion criteria. The majority of reports showed the presence of estrogen and progesterone receptors in astrocytomas. Overall, higher tumor grades were associated with decreased estrogen receptor expression and increased progesterone receptor expression.

  17. Stereotactic Radiosurgery for Recurrent or Unresectable Pilocytic Astrocytoma

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    Hallemeier, Christopher L. [Department of Radiation Oncology, Mayo Clinic, Rochester, MN (United States); Pollock, Bruce E. [Department of Radiation Oncology, Mayo Clinic, Rochester, MN (United States); Department of Neurological Surgery, Mayo Clinic, Rochester, MN (United States); Schomberg, Paula J. [Department of Radiation Oncology, Mayo Clinic, Rochester, MN (United States); Link, Michael J. [Department of Neurological Surgery, Mayo Clinic, Rochester, MN (United States); Brown, Paul D. [Department of Radiation Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX (United States); Stafford, Scott L., E-mail: Stafford.scott@mayo.edu [Department of Radiation Oncology, Mayo Clinic, Rochester, MN (United States)

    2012-05-01

    Purpose: To report the outcomes in patients with recurrent or unresectable pilocytic astrocytoma (PA) treated with Gamma Knife stereotactic radiosurgery (SRS). Methods and Materials: Retrospective review of 18 patients (20 lesions) with biopsy-confirmed PA having SRS at our institution from 1992 through 2005. Results: The median patient age at SRS was 23 years (range, 4-56). Thirteen patients (72%) had undergone one or more previous surgical resections, and 10 (56%) had previously received external-beam radiation therapy (EBRT). The median SRS treatment volume was 9.1 cm{sup 3} (range, 0.7-26.7). The median tumor margin dose was 15 Gy (range, 12-20). The median follow-up was 8.0 years (range, 0.5-15). Overall survival at 1, 5, and 10 years after SRS was 94%, 71%, and 71%, respectively. Tumor progression (local solid progression, n = 4; local solid progression + distant, n = 1; distant, n = 2; cyst development/progression, n = 4) was noted in 11 patients (61%). Progression-free survival at 1, 5, and 10 years was 65%, 41%, and 17%, respectively. Prior EBRT was associated with inferior overall survival (5-year risk, 100% vs. 50%, p = 0.03) and progression-free survival (5-year risk, 71% vs. 20%, p = 0.008). Nine of 11 patients with tumor-related symptoms improved after SRS. Symptomatic edema after SRS occurred in 8 patients (44%), which resolved with short-term corticosteroid therapy in the majority of those without early disease progression. Conclusions: SRS has low permanent radiation-related morbidity and durable local tumor control, making it a meaningful treatment option for patients with recurrent or unresectable PA in whom surgery and/or EBRT has failed.

  18. Imaging Features of Pilocytic Astrocytoma in Cerebral Ventricles.

    Science.gov (United States)

    Xia, Jg; Yin, B; Liu, L; Lu, Yp; Geng, Dy; Tian, Wz

    2016-09-01

    Our aim was to identify imaging characteristics of pilocytic astrocytomas (PAs) in the cerebral ventricles to help radiologists distinguish PAs from other brain tumors preoperatively. Twelve postsurgery patients with a pathological PA diagnosis were included. Among them, 10 had submitted to surgery based on 3.0-T magnetic resonance imaging sequences and 7 because of computed tomography (CT) results. We analyzed their clinical and radiological records retrospectively. The 12 patients (7 were male) had 13 lesions (11 with a single focus, 1 with multiple foci). Average age was 26.5 years (range, 6-49 years). Clinical symptoms included headache, dizziness, vomiting, and unstable gait. Tumor locations were the lateral ventricle (4), fourth ventricle (7), or both ventricles (1, but multifocal). One tumor had disseminated. PA diameters were 18.7-63.0 mm (mean ± standard deviation, 36.5 ± 12.4 mm). Nine had a round margin, and four had irregular margins. Two were cystic lesions. Eleven were mixed cystic and solid. CT showed the tumors as low-density masses. Two had calcifications. Their cystic portions showed low signal intensity (SI) on T1-weighted imaging (T1WI) and high SI on T2-weighted imaging (T2WI). The cystic walls and solid portions of the PAs showed slightly low SI on T1WI and slightly high SI on T2WI. After gadopentetate dimeglumine administration, the solid portion showed heterogeneous enhancement, whereas the cystic portion showed no enhancement. Radiological features of intraventricular and extraventricular PAs were similar to typical ones, including enhanced nodules within cysts. Radiological findings can usually diagnose PAs correctly.

  19. Management of optic chiasmatic/hypothalamic astrocytomas in children

    Energy Technology Data Exchange (ETDEWEB)

    Steinbok, P.; Hentschel, S.; Almqvist, P.; Cochrane, D.D. [Univ. of British Columbia, British Columbia' s Children' s Hospital, Div. of Pediatric Neurosurgery, Dept. of Surgery, Vancouver, British Columbia (Canada); Poskitt, K. [Univ. of British Columbia, British Columbia' s Children' s Hospital, Dept. of Radiology, Vancouver, British Columbia (Canada)

    2002-05-01

    The management of optic chiasmatic gliomas is controversial, partly related to failure to separate out those tumors involving the optic chiasm only (chiasmatic tumors) from those also involving the hypothalamus (chiasmatic/hypothalamic tumors). The purpose of this study was: (i) to analyze the outcomes of chiasmatic and chiasmatic/hypothalamic tumors separately; and (ii) to determine the appropriateness of recommending radical surgical resection for the chiasmatic/hypothalamic tumors. A retrospective chart review of all newly diagnosed tumors involving the optic chiasm from 1982-1996 at British Columbia's Children's Hospital was performed. There were 32 patients less than 16 years of age, 14 with chiasmatic and 18 with chiasmatic/hypothalamic astrocytomas, with an average duration of follow-up of 5.8 years and 6.3 years, respectively. Ten of the patients with chiasmatic tumors and none with chiasmatic/hypothalamic tumors had neurofibromatosis I. Thirteen of the 14 chiasmatic tumors were managed with observation only, and none had progression requiring active intervention. For the chiasmatic/hypothalamic tumors. eight patients had subtotal resections (>95% resection), six had partial resections (50-95%), three had limited resections (<50%), and one had no surgery. There were fewer complications associated with the limited resections, especially with respect to hypothalamic dysfunction. There was no correlation between the extent of resection (subtotal, partial, or limited) and the time to tumor progression (average 18 months). In conclusion, chiasmatic and chiasmatic/hypothalamic tumors are different entities, which should be separated out for the Purposes of any study. For the chiasmatic/hypothalamic tumors, there was more morbidity and no prolongation of time to progression when radical resections were compared to more limited resections. Therefore, if surgery is performed, it may be appropriate to do a surgical procedure that strives only to provide a

  20. Hydrogel Environment Supports Cell Culture Expansion of a Grade IV Astrocytoma.

    Science.gov (United States)

    Jogalekar, Manasi P; Cooper, Leigh G; Serrano, Elba E

    2017-09-01

    Malignant astrocytomas are aggressive cancers of glial origin that can develop into invasive brain tumors. The disease has poor prognosis and high recurrence rate. Astrocytoma cell lines of human origin are an important tool in the experimental pathway from bench to bedside because they afford a convenient intermediate system for in vitro analysis of brain cancer pathogenesis and treatment options. We undertook the current study to determine whether hydrogel culture methods could be adapted to support the growth of astrocytoma cell lines, thereby facilitating a system that may be biologically more similar to in vivo tumor tissue. Our experimental protocols enabled maintenance of Grade IV astrocytoma cell lines in conventional monolayer culture and in the extracellular matrix hydrogel, Geltrex™. Light and fluorescence microscopy showed that hydrogel environments promoted cellular reorganization from dispersed cells into multilayered aggregates. Transmission electron microscopy revealed the prevalence of autophagy and nuclear membrane distortions in both culture systems. Analysis of microarray Gene Expression Omnibus (GEO) DataSets highlighted expression of genes implicated in pathways for cancer progression and autophagy. A pilot quantitative polymerase chain reaction (qPCR) analysis of the autophagic biomarkers, Beclin 1 (BECN1) and microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B), with two reference genes (beta actin, ACTB; glyceraldehyde 3-phosphate dehydrogenase, GAPDH), uncovered a relative increase of BECN1 and LC3B in hydrogel cultures of astrocytoma as compared to the monolayer. Taken together, results establish that ultrastructural and molecular characteristics of autophagy are features of this astrocytoma cell line, and that hydrogel culture systems can afford novel opportunities for in vitro studies of glioma.

  1. Conformal proton radiation therapy for pediatric low-grade astrocytomas

    Energy Technology Data Exchange (ETDEWEB)

    Hug, E.B. [Loma Linda Univ. Medical Center, Loma Linda, CA (United States). Dept. of Radiation Medicine; Loma Linda Univ. Medical Center, Loma Linda, CA (United States). Dept. of Pediatrics and Dept. of Pathology; Darthmouth-Hitchcock Medical Center, Lebanon, New Hampshire (United States). Section of Radiation Oncology; Muenter, M.W.; Archambeau, J.O.; DeVries, A.; Loredo, L.N.; Grove, R.I.; Slater, J.D. [Loma Linda Univ. Medical Center, Loma Linda, CA (United States). Dept. of Radiation Medicine; Liwnicz, B. [Loma Linda Univ. Medical Center, Loma Linda, CA (United States). Dept. of Pathology

    2002-01-01

    Background: To evaluate the safety and efficacy of proton radiation therapy (PRT) for intracranial low-grade astrocytomas, the authors analyzed the first 27 pediatric patients treated at Loma Linda University Medical Center (LLUMC). Patients and Method: Between September 1991 and August 1997, 27 patients (13 female, 14 male) underwent fractionated proton radiation therapy for progressive or recurrent low-grade astrocytoma. Age at time of treatment ranged from 2 to 18 years (mean: 8.7 years). Tumors were located centrally (diencephatic) in 15 patients, in the cerebral and cerebellar hemispheres in seven patients, and in the brainstem in five patients. 25/27 patients (92%) were treated for progressive, unresectable, or residual disease following subtotal resection. Tissue diagnosis was available in 23/27 patients (85%). Four patients with optic pathway tumors were treated without histologic confirmation. Target doses between 50.4 and 63.0 CGE (cobalt gray equivalent, mean: 55.2 CGE) were prescribed at 1.8 CGE per fraction, five treatments per week. Results: At a mean follow-up period of 3.3 years (0.6-6.8 years), 6/27 patients experienced local failure (all located within the irradiated field), and 4/27 patients had died. By anatomic site these data translated into rates of local control and survival of 87% (13/15 patients) and 93% (14/15 patients) for central tumors, 71% (5/7 patients) and 86% (6/7 patients) for hemispheric tumors, and 60% (3/5 patients) and 60% (3/5 patients) for tumors located in the brainstem. Proton radiation therapy was generally well tolerated. All children with local control maintained their performance status. One child with associated neurofibromatosis, Type 1, developed Moyamoya disease. All six patients with optic pathway tumors and useful vision maintained or improved their visual status. Conclusions: This report on pediatric low-grade astrocytomas confirms proton radiation therapy as a safe and efficacious 3-D conformal treatment

  2. Elevated expression of HSP10 protein inhibits apoptosis and associates with poor prognosis of astrocytoma.

    Science.gov (United States)

    Fan, Weibing; Fan, Shuang-Shi; Feng, Juan; Xiao, Desheng; Fan, Songqing; Luo, Jiadi

    2017-01-01

    Astrocytoma is the most common type of primary malignant brain tumor, with pretty lowly 5-year survival rate in patients. Although extended surgical removal of the tumor and postoperative chemotherapy/radiotherapy executed, still there is large recurrence rate, mainly because diffuse glioma tumor cells ubiquitously infiltrate into normal parenchyma. So it becomes a priority to hunt novel molecular and signaling pathway targets to suppress astrocyma progression. HSP10, an important member of Heat shock proteins (Hsps) family, classically works as molecular chaperone folding or degradating of target proteins. Evolutionarily, HSP10 is also reported to be involved in immunomodulation and tumor progression. Poly (ADP-ribose) polymerase (PARP), important in DNA repair, is one of the main cleavage targets of caspase. And cleaved PARP (c-PARP) can serve as a marker of cells undergoing apoptosis. So far, whether the expression of HSP10 or c-PARP is associated with clinicopathologic implication for astrocytoma has not been reported. Meanwhile, it is unclear about the relationship between HSP10 and cell apoptosis. The purpose of this research is to elucidate the association between the expression of HSP10 and c-PARP and clinicopathological characteristics of astrocytoma by immunohistochemistry. The results showed that positive percentage of high HSP10 expression in astrocytoma 42/103, 40.8%) was significantly higher than that in the non-tumor control brain tissues (8/43, 18.6%) (P = 0.01). While no apparent difference of high c-PARP expression existed between astrocytoma and non-tumor control brain tissues. Furthermore, elevated expression of HSP10 was negative related to low expression of c-PARP (r = -0.224, P = 0.023), indicating high expression of HSP10 in astrocytoma inhibited apoptosis process effectively. And overexpression of HSP10 was proved to be the independent poor prognostic factor for astrocytoma by multivariate analysis. Taken together, our results suggest that

  3. Regression of Subependymal Giant Cell Astrocytoma With Rapamycin in Tuberous Sclerosis Complex

    Science.gov (United States)

    Koenig, Mary Kay; Butler, Ian J.; Northrup, Hope

    2011-01-01

    The authors present a 21-year-old woman who has been receiving rapamycin for 5 months for bilateral subependymal giant cell astrocytomas. The patient was started at a dose of 0.2 mg/kg/day. Levels were maintained between 11 and 13 ng/mL. Magnetic resonance imaging of the brain 2½ months after initiating rapamycin demonstrated a decrease in size of both astrocytomas (11 to 7.5 mm on the right and 8 to 5 mm on the left). Further studies are needed with prolonged observation to confirm these findings, determine the length of necessary treatment, and evaluate recurrence risk after discontinuation of rapamycin. PMID:18952591

  4. Prognostic relevance of gemistocytic grade II astrocytoma: gemistocytic component and MR imaging features compared to non-gemistocytic grade II astrocytoma

    Energy Technology Data Exchange (ETDEWEB)

    Heo, Young Jin [Inje University, Busan Paik Hospital, Department of Radiology, Busan (Korea, Republic of); Park, Ji Eun; Kim, Ho Sung; Lee, Ji Ye; Jung, Seung Chai; Choi, Choong Gon; Kim, Sang Joon [University of Ulsan College of Medicine, Asan Medical Center, Department of Radiology and Research Institute of Radiology, Seoul (Korea, Republic of); Nam, Soo Jeong [University of Ulsan College of Medicine, Asan Medical Center, Department of Pathology, Seoul (Korea, Republic of)

    2017-07-15

    To determine if gemistocytic grade II astrocytoma (GemA) and its MR imaging characteristics are associated with a shorter time-to-progression (TTP) compared with non-gemistocytic grade II astrocytoma (non-GemA). We enrolled 78 patients who were followed up more than 5 years (29 pathologically proven GemA and 49 non-GemA) during a 10-year period. Contrast-enhanced T1-weighted, diffusion-weighted imaging (DWI), dynamic susceptibility contrast (DSC), and MR spectroscopy (MRS) and clinical data were retrospectively reviewed. Clinical and MR imaging features were analyzed as possible prognostic factors of high-grade transformation, and multivariate analysis of TTP was performed using Cox proportional modeling. GemA showed more frequent high-grade features than non-GemA, including diffusion restriction (P <.001), increased choline/creatine (P =.02), and increased choline/NAA ratio (P =.015). Patients with GemA had a significantly shorter median TTP (53.1 vs 68 months; P <.001). A gemistocytic histopathology (hazard ratio = 3.42; P =.015) and low ADC (hazard ratio = 3.61; P =.001) were independently associated with a shorter TTP. GemA can present with MR imaging findings mimicking high-grade glioma at initial diagnosis and transforms to high-grade disease earlier than non-GemA. Low ADC on DWI might be useful in stratifying the risk of progression in patients with grade II astrocytoma. (orig.)

  5. Differential expression of two fibroblast growth factor-receptor genes is associated with malignant progression in human astrocytomas

    Energy Technology Data Exchange (ETDEWEB)

    Yamaguchi, F.; Saya, H.; Bruner, J.M.; Morrison, R.S. (Univ. of Texas M.D. Anderson Cancer Center, Houston, TX (United States))

    1994-01-18

    Malignant astrocytomas, which are highly invasive, vascular neoplasms, compose the majority of nervous system tumors in humans. Elevated expression of fibroblast growth factors (FGFs) in astrocytomas has implicated the FGF family of mitogens in the initiation and progression of astrocyte-derived tumors. In this study, the authors demonstrated that human astrocytomas undergo parallel changes in FGF-receptor (FGFR) expression during their progression from a benign to a malignant phenotype. FGFR type 2 (BEK) expression was abundant in normal white matter and in all low-grade astrocytomas but was not seen in malignant astrocytomas. Conversely, FGFR type 1 (FLG) expression was absent or barely detectable in normal white matter but was significantly elevated in malignant astrocytomas. Malignant astrocytomas also expressed an alternatively spliced form of FGFR-1 (FGFR-1[beta]) containing two immunoglobulin-like disulfide loops, whereas normal human adult and fetal brains expressed a receptor form (FGFR-1[alpha]) containing three immunoglobulin-like disulfide loops. Intermediate grades of astrocytic tumors exhibited a gradual loss of FGFR-2 and a shift in expression from FGFR-1[alpha] to FGFR-2 and a shift in expression from FGFR-1[alpha] to FGFR-1[beta] as they progressed from benign to malignant phenotype. These results suggest that differential expression and alternative splicing of FGFRs may be critical in the malignant progression of astrocytic tumors.

  6. The relationship between MRI quantitative parameters and the expression of hypoxia inducible factor-1 alpha in cerebral astrocytoma.

    Science.gov (United States)

    Shu, Chang; Wang, Jinhuan

    2017-02-01

    Astrocytoma is the common type of glioma. But the MRI scanning for astrocytoma preoperation pathological diagnosis is not exact. The purpose of this study was to use the MRI multi quantitative parameters to improve the diagnosis of astrocytoma and exploit their molecular mechanism related to the expression of HIF-1α. Superconducting MR scanner and its work station were used to calculate the MRI multi quantitative parameters of the selected patients in this experiment. Scion Image Beta4.03 software was used to get the cellular density of tumor tissue. The expression of HIF-1α in astrocytoma specimens was detected by immunohistochemistry method. The correlation of MRI multi quantitative parameters and the expression of HIF-1α was analyzed by statistical software. The values of ADC, RSIGd, EP, EI, cellular density and the expression of HIF-1α were changed with the malignant degree of astrocytoma to some extent, but not every quantitative parameter was related to the expression of HIF-1α. The MRI multi quantitative parameters binding with conventional MRI imaging can significantly raise the diagnostic accuracy of astrocytoma preoperatively. MRI features could indirectly reflect the biological behavior of astrocytoma. The peritumoral edema can't be explained by only one theory. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Gene Expression Profiling of Chemokines and Their Receptors in Low and High Grade Astrocytoma

    Science.gov (United States)

    Sharma, Ira; Singh, Avninder; Sharma, Karam Chand; Saxena, Sunita

    2017-05-01

    Background: Despite intense interest in molecular characterization and searches for novel therapeutic targets, the glioblastoma remains a formidable clinical challenge. Among many contributors to gliomagenesis, chemokines have drawn special attention due to their involvement in a plethora of biological processes and pathological conditions. In the present study we aimed to elucidate any pro-gliomagenic chemokine axis and probable roles in development of glioblastoma multiforme (GBM). Method: An array of 84 chemokines, chemokine receptors and related genes were studied by real time PCR with comparison between low grade astrocytoma (diffuse astrocytoma – grade II) and high grade astrocytoma (glioblastoma multiforme – grade IV). Gene ontology analysis and database mining were performed to funnel down the important axis in GBM followed by validation at the protein level by immunohistochemistry on tissue microarrays. Results: Gene expression and gene ontology analysis identified CXCL8 as an important chemokine which was more frequently up-regulated in GBM as compared to diffuse astrocytoma. Further we demonstrated localization of CXCL8 and its receptors in glioblastoma possibly affecting autocrine and paracrine signalling that promotes tumor cell proliferation and neovascularisation with vascular mimicry. Conclusion: From these results CXCL8 appears to be an important gliomagenic chemokine which may be involved in GBM growth by promoting tumor cell proliferation and neovascularization via vascular mimicry. Further in vitro and in vivo investigations are required to explore its potential candidature in anti-GBM therapy. Creative Commons Attribution License

  8. Tumour vasculature and angiogenic profile of paediatric pilocytic astrocytoma; is it much different from glioblastoma?

    NARCIS (Netherlands)

    Sie, M.; de Bont, E. S. J. M.; Scherpen, F. J. G.; Hoving, E. W.; den Dunnen, W. F. A.

    2010-01-01

    Aims: Pilocytic astrocytomas are the most frequent brain tumours in children. Because of their high vascularity, this study aimed to obtain insights into potential angiogenic related therapeutic targets in these tumours by characterization of the vasculature and the angiogenic profile. In this study

  9. Tracer transport and metabolism in a patient with juvenile pilocytic astrocytoma. A PET study

    NARCIS (Netherlands)

    Roelcke, U; Radu, EW; Hausmann, O; Vontobel, P; Maguire, RP; Leenders, KL

    We studied a patient with juvenile pilocytic astrocytoma (JPA) using positron emission tomography (PET), F-18-fluorodeoxyglucose (FDG), C-11-methionine (MET), and (82)Rubidium (RUB). Non-linear fitting and multiple time graphical plotting of the dynamic PET data revealed values for tumor plasma

  10. Rapid malignant transformation of low-grade astrocytoma in a pregnant woman.

    Science.gov (United States)

    Hanada, Tomoko; Rahayu, Tri Uji; Yamahata, Hitoshi; Hirano, Hirofumi; Yoshioka, Takako; Arita, Kazunori

    2016-10-01

    We report rapid malignant transformation of diffuse astrocytoma to glioblastoma during pregnancy in a young woman. A 21-year-old woman was found to have a non-enhancing right frontal lesion, supposed to be a low-grade astrocytoma according to magnetic resonance imaging (MRI) studied for chronic headache. Due to the absence of clinical symptoms, the patient refused further investigations and delivered a baby and then became pregnant with a second baby. At first, she refused the biopsy because she was afraid, although the size of the lesion on MRI was increasing; however, due to repeated persuasion, she underwent a biopsy during the 4th month of her second gestation, with a result of diffuse astrocytoma (WHO grade II). At 1 month after the second delivery and 6 months after the biopsy, MRI revealed further enlargement of the tumor and a heterogeneous kenhancement effect. A gross tumor removal was carried out, and the tumor was histologically diagnosed as glioblastoma (WHO grade IV). This is the quickest ever malignant transformation of diffuse astrocytoma during pregnancy in the published reports. © 2016 Japan Society of Obstetrics and Gynecology.

  11. Vascular Endothelial Growth Factor as an Angiogenic Marker in Malignant Astrocytoma and Oligodendroglioma: An Indian Scenario

    Science.gov (United States)

    Vokuda, Ramya S; Srinivas, Bheemanathi Hanuman; Madhugiri, Venkatesh S

    2017-01-01

    Introduction The role of Vascular Endothelial Growth Factor (VEGF) in angiogenesis has been extensively studied in gliomas, such as astrocytoma and oligodendrogliomas, worldwide. However, there is limited information available with regard to the Indian population. Aim To study, whether VEGF is expressed in the Indian population in a pattern similar to that in other population. Materials and Methods In this prospective study approved by the Institute Ethics Committee for Human Studies at Jawaharlal Institute of Post Graduate Medical Education and Research (JIPMER) the patients operated for glioma in 2014 and 2015 (n = 60) were included. Tumours were graded as per the World Health Organization (WHO) grading system. VEGF expression in various grades was analysed using immunohistochemistry. Results Of the 60 patients included in this study, 15 were Grade II- (diffuse astrocytomas – 12; oligodendrogliomas- 3), 15 were Grade III-(anaplastic astrocytomas- 2; anaplastic oligodendrogliomas – 13) and 30 were Grade IV-glioblastomas. For VEGF antibody staining, two patients (3.33%) showed negative results and 58 patients (96%) showed positive results. VEGF positivity was 100% in Grade II and III, while it was 93.3% (28/30) in Grade IV tumours (p=0.012). Conclusion The expression of VEGF was associated with the grade of tumour, which gradually increased from Grade II to Grade IV. We conclude that VEGF-regulated angiogenesis plays an important role in tumour progression of astrocytomas and oligodendrogliomas in the Indian population as observed worldwide. PMID:28384867

  12. Imaging Manifestations of a Subependymal Giant Cell Astrocytoma in Tuberous Sclerosis

    OpenAIRE

    Stein, Joseph R.; Reidman, Daniel A.

    2016-01-01

    Tuberous sclerosis is a rare genetic disorder resulting in benign tumor growth in various organs including the brain, heart, skin, eyes, kidney, and lung as well as systemic manifestations including seizures, cognitive impairment, and dermatologic abnormalities. This report shows the radiological findings and differentiation between a subependymal nodule and subependymal giant cell astrocytoma in a patient with tuberous sclerosis presenting with new onset seizures.

  13. Gene Expression Profiling of Chemokines and Their Receptors in Low and High Grade Astrocytoma

    Science.gov (United States)

    Sharma, Ira; Singh, Avninder; Sharma, Karam Chand; Saxena, Sunita

    2017-01-01

    Background: Despite intense interest in molecular characterization and searches for novel therapeutic targets, the glioblastoma remains a formidable clinical challenge. Among many contributors to gliomagenesis, chemokines have drawn special attention due to their involvement in a plethora of biological processes and pathological conditions. In the present study we aimed to elucidate any pro-gliomagenic chemokine axis and probable roles in development of glioblastoma multiforme (GBM). Method: An array of 84 chemokines, chemokine receptors and related genes were studied by real time PCR with comparison between low grade astrocytoma (diffuse astrocytoma – grade II) and high grade astrocytoma (glioblastoma multiforme – grade IV). Gene ontology analysis and database mining were performed to funnel down the important axis in GBM followed by validation at the protein level by immunohistochemistry on tissue microarrays. Results: Gene expression and gene ontology analysis identified CXCL8 as an important chemokine which was more frequently up-regulated in GBM as compared to diffuse astrocytoma. Further we demonstrated localization of CXCL8 and its receptors in glioblastoma possibly affecting autocrine and paracrine signalling that promotes tumor cell proliferation and neovascularisation with vascular mimicry. Conclusion: From these results CXCL8 appears to be an important gliomagenic chemokine which may be involved in GBM growth by promoting tumor cell proliferation and neovascularization via vascular mimicry. Further in vitro and in vivo investigations are required to explore its potential candidature in anti-GBM therapy. PMID:28610419

  14. Expression of the lysosomal-associated membrane protein-1 (LAMP-1) in astrocytomas

    DEFF Research Database (Denmark)

    Jensen, Stine S; Aaberg-Jessen, Charlotte; Christensen, Karina G

    2013-01-01

    astrocytomas and compared with tumor grade and overall patient survival. Moreover, double immunofluorescence stainings were performed with LAMP-1 and the astrocytic marker GFAP and the putative stem cell marker CD133 on ten glioblastomas. Most tumors expressed the LAMP-1 protein in the cytoplasm of the tumor...

  15. Recurrent somatic alterations of FGFR1 and NTRK2 in pilocytic astrocytoma

    Science.gov (United States)

    Jones, David T.W.; Hutter, Barbara; Jäger, Natalie; Korshunov, Andrey; Kool, Marcel; Warnatz, Hans-Jörg; Zichner, Thomas; Lambert, Sally R.; Ryzhova, Marina; Quang, Dong Anh Khuong; Fontebasso, Adam M.; Stütz, Adrian M.; Hutter, Sonja; Zuckermann, Marc; Sturm, Dominik; Gronych, Jan; Lasitschka, Bärbel; Schmidt, Sabine; Şeker-Cin, Huriye; Witt, Hendrik; Sultan, Marc; Ralser, Meryem; Northcott, Paul A.; Hovestadt, Volker; Bender, Sebastian; Pfaff, Elke; Stark, Sebastian; Faury, Damien; Schwartzentruber, Jeremy; Majewski, Jacek; Weber, Ursula D.; Zapatka, Marc; Raeder, Benjamin; Schlesner, Matthias; Worth, Catherine L.; Bartholomae, Cynthia C.; von Kalle, Christof; Imbusch, Charles D.; Radomski, Sylwester; Lawerenz, Chris; van Sluis, Peter; Koster, Jan; Volckmann, Richard; Versteeg, Rogier; Lehrach, Hans; Monoranu, Camelia; Winkler, Beate; Unterberg, Andreas; Herold-Mende, Christel; Milde, Till; Kulozik, Andreas E.; Ebinger, Martin; Schuhmann, Martin U.; Cho, Yoon-Jae; Pomeroy, Scott L.; von Deimling, Andreas; Witt, Olaf; Taylor, Michael D.; Wolf, Stephan; Karajannis, Matthias A.; Eberhart, Charles G.; Scheurlen, Wolfram; Hasselblatt, Martin; Ligon, Keith L.; Kieran, Mark W.; Korbel, Jan O.; Yaspo, Marie-Laure; Brors, Benedikt; Felsberg, Jörg; Reifenberger, Guido; Collins, V. Peter; Jabado, Nada; Eils, Roland; Lichter, Peter; Pfister, Stefan M.

    2014-01-01

    Pilocytic astrocytoma, the most common childhood brain tumor1, is typically associated with mitogen-activated protein kinase (MAPK) pathway alterations2. Surgically inaccessible midline tumors are therapeutically challenging, showing sustained tendency for progression3 and often becoming a chronic disease with substantial morbidities4. Here we describe whole-genome sequencing of 96 pilocytic astrocytomas, with matched RNA sequencing (n=73), conducted by the International Cancer Genome Consortium (ICGC) PedBrain Tumor Project. We identified recurrent activating mutations in FGFR1 and PTPN11 and novel NTRK2 fusion genes in non-cerebellar tumors. New BRAF activating changes were also observed. MAPK pathway alterations affected 100% of tumors analyzed, with no other significant mutations, indicating pilocytic astrocytoma as predominantly a single-pathway disease. Notably, we identified the same FGFR1 mutations in a subset of H3F3A-mutated pediatric glioblastoma with additional alterations in NF15. Our findings thus identify new potential therapeutic targets in distinct subsets of pilocytic astrocytoma and childhood glioblastoma. PMID:23817572

  16. Pilocytic astrocytoma of the cerebellopontine angle mimicking vestibular schwannoma: report of a rare entity.

    Science.gov (United States)

    Dutta, Gautam; Singh, Daljit; Singh, Hukum; Sachdeva, Deepashu; Kumar, Vikas; Chaturvedi, Ashutosh

    2017-12-26

    We present a rare case of a 55-yr old patient of pilocytic astrocytoma of the cerebello-pontine angle mimicking a vestibular schwannoma. The tumor protruded into the porus acusticus causing enlargement of the internal auditory meatus, which is quite an unusual feature of glial tumours.

  17. [Pilocytic astrocytoma of the cerebrum presenting in an elderly patient: a case report].

    Science.gov (United States)

    Yoshida, Yuya; Tsukada, Toshiyuki; Hashimoto, Masaaki; Hayashi, Yutaka

    2011-09-01

    We report a case of pilocytic astrocytoma of the cerebrum presenting in an elderly patient. A 76-year-old man was admitted to our department due to the development of dysarthria. MRI showed a cystic mass with an enhanced small mural nodule in the left frontal lobe. At surgery, the cyst contents were aspirated, and the mural nodule was excised. Histological examination showed a pattern that is usually seen in pilocytic astrocytoma of the cerebellum, including loose and compact areas composed of pilocytic and stellate cells, a few eosinophilic granular bodies, but not Rosenthal fibers. Pilocytic astrocytoma is a common type of pediatric brain tumor that can arise within either the cerebellum or the hypothalamic/chiasmatic region, but rarely seen in the cerebral hemisphere at an advanced age. To our knowledge, only 45 cases of pilocytic astrocytoma of the cerebrum developing in an adult are reported. In those cases, the symptoms of the disease developed during the third decade of life. The onset at a most advanced age as in the present case is thought to be extremely rare.

  18. Recurrent astrocytoma in a child : A report of cytogenetics and TP53 gene mutation screening

    NARCIS (Netherlands)

    Dam, A.; Fock, Johanna M.; Hayes, VM; Molenaar, WM; van den Berg, E

    An 8-year-old girl presented with a cerebral tumor and 3 recurrences within 15 months, The primary tumor was a low-grade astrocytoma, but the recurrences showed progressively malignant phenotypes with increasing mitotic activity and MIB-1 labeling indices. Radiotherapy was given between the first

  19. Progesterone promotes cell migration, invasion and cofilin activation in human astrocytoma cells.

    Science.gov (United States)

    Piña-Medina, Ana Gabriela; Hansberg-Pastor, Valeria; González-Arenas, Aliesha; Cerbón, Marco; Camacho-Arroyo, Ignacio

    2016-01-01

    Astrocytomas are the most common and aggressive primary brain tumors in humans. Invasiveness of these tumors has been attributed in part to deregulation of cell motility-dependent cytoskeletal dynamics that involves actin-binding proteins such as cofilin. Progesterone (P4) has been found to induce migration and invasion of cells derived from breast cancer and endothelium. However, the role of P4 in migration and invasion of astrocytoma cells as well as its effects on astrocytomas cytoskeleton remodeling is not known. In this work we evaluated these aspects in D54 and U251 cells derived from human astrocytomas from the highest degree of malignancy (grade IV, glioblastoma). Our results showed that in scratch-wound assays P4 increased the number of D54 and U251 cells migrating from 3 to 48 h. Both RU486, a P4 receptor (PR) antagonist, and an oligonucleotide antisense against PR significantly blocked P4 effects. Transwell assays showed that P4 significantly increased the number of invasive cells at 24h. As in the case of migration, this effect was blocked by RU486. Finally, by Western blotting, an increase in the cofilin/p-cofilin ratio at 15 and 30 min and a decrease at 30 and 60 min in U251 and D54 cells, respectively, was observed after P4, P4+RU486 and RU486 treatments. These data suggest that P4 increases human astrocytoma cells migration and invasion through its intracellular receptor, and that cofilin activation by P4 is independent of PR action. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. LOX expression and functional analysis in astrocytomas and impact of IDH1 mutation.

    Directory of Open Access Journals (Sweden)

    Roseli da Silva

    Full Text Available Lysyl oxidase (LOX is involved in vital biological processes such as cell motility, cell signaling and gene regulation. Deregulation of this protein can contribute to tumor formation and progression. Although it is known that LOX is involved in invasion, proliferation and tumor migration in other types of tumors, studies of LOX in astrocytomas of different grades are scarce. The purpose of our study was to characterize LOX, BMP1 and HIF1A expression by real-time PCR in astrocytomas with WHO grades I to IV compared to non-neoplastic brain tissue. IDH1 mutational status was determined by PCR and sequencing. LOX protein expression was also analyzed by immunohistochemistry. LOX functional analyses were performed using siRNA knockdown and the specific inhibitor BAPN in two glioblastoma cell lines. The expression levels of LOX, BMP1 and HIF1A were correlated and analyzed according to IDH1 mutation status and to the clinical end-point of overall survival of glioblastoma patients. The results demonstrate that increased expression and activity of LOX, BMP1 and HIF1A were positively correlated with the malignant grade of astrocytomas. LOX protein expression also increased according to the degree of malignancy, with localization in the cytoplasm and nucleus and staining observed in endothelial cells. Glioblastoma with a mutation in IDH1 expressed lower levels of LOX in the nucleus, and IDH1-mutated cases showed lower LOX expression levels when compared to wild-type IDH1 cases. LOX knockdown and inhibition by BAPN in U87MG and A172 cell lines affected migration, invasion and soft agar colony formation. Taken together, these results corroborate the role of LOX in the migration, invasion and angiogenesis of astrocytomas. Furthermore, LOX expression is influenced by IDH1 mutational status. This work provides new insights for researchers aiming to design targeted therapies to control astrocytomas.

  1. Surgical and clinical aspects of cerebellar pilomyxoid-spectrum astrocytomas in children.

    Science.gov (United States)

    El Beltagy, Mohamed A; Atteya, Mostafa M E; El-Haddad, Alaa; Awad, Madiha; Taha, Hala; Kamal, Mohamed; El Naga, Sherif Abou

    2014-06-01

    Cerebellar pilomyxoid astrocytomas (PMAs) and intermediate pilomyxoid astrocytomas (IPAs) are collectively called "pilomyxoid-spectrum astrocytomas (PMSAs)." Cerebellar PMSAs are thought to behave more aggressively than pilocytic astrocytomas (PAs). Our objective is to compare PMSAs to PAs in terms of surgical and clinical profiles. This retrospective study included 66 cases (35 males and 31 females) with cerebellar astrocytomas treated between July 2007 and December 2012 at Children's Cancer Hospital Egypt (CCHE 57357) with a mean age of 7 (±1.5) years. Cases were divided into three subgroups as follows: 44 PAs, 10 IPAs, and 12 PMAs. Comparison between all groups was focusing on brain stem invasion, intrinsic necrotic cavitation, extent of resection, recurrence, leptomeningeal dissemination (LD), metastases, need for CSF diversion, and cerebellar mutism (CM). Cerebellar PMAs and IPAs separately and collectively had higher incidence of brain stem invasion, intrinsic necrotic cavitation, tumor recurrence, and LD when compared to PAs (P < 0.001). Gross total resection was 13.6 % in PMSAs versus 90.9 % in PAs (P < 0.001). PMAs had a higher incidence of tumor recurrence than IPAs (66.7 versus 20 %, P < 0.001). Incidence of recurrence in PAs was 9.1 % in partially resected cases. Mean interval to recurrence was 9 (±1.5) months in PMSAs and 42 (±2) months in PAs. Cerebellar PMSAs express an aggressive clinical behavior and impose more operative challenges than PAs. These tumors may represent a clinical spectrum-at its benign end lies PA, while PMA lies at the aggressive end, with IPA lying just behind. Such concepts could be used to guide management in the future.

  2. Unusual presentation of unilateral intra-orbital optic nerve pilocytic astrocytoma of the juvenile type in a geriatric patient.

    Science.gov (United States)

    Dua, Sonal; Sharma, Kanika; Juneja, Rakesh; Kalakoti, Piyush; Kamble, Mala; Subramanian, Prem

    2016-03-01

    Optic nerve gliomas (ONG) are rare and seldom encountered in clinical practice. The pilocytic (astrocytoma) variant of ONG almost always presents during the first two decades of life. In this report, the authors discuss an unusual presentation of pilocytic astrocytoma of the juvenile type in an elderly Indian male. With this unusual presentation, ONG affecting the visual pathway should be considered as a possible differential of visual diminution in the elderly population. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Stereotaxic gamma knife surgery in treatment of critically located pilocytic astrocytoma: preliminary result

    Directory of Open Access Journals (Sweden)

    Hafez Raef FA

    2007-03-01

    Full Text Available Abstract Background Low-grade gliomas are uncommon primary brain tumors, located more often in the posterior fossa, optic pathway, and brain stem and less commonly in the cerebral hemispheres. Case presentations Two patients with diagnosed recurrent cystic pilocytic astrocytoma critically located within the brain (thalamic and brain stem were treated with gamma knife surgery. Gamma knife surgery (GKS did improve the patient's clinical condition very much which remained stable later on. Progressive reduction on the magnetic resonance imaging (MRI studies of the solid part of the tumor and almost disappearance of the cystic component was achieved within the follow-up period of 36 months in the first case with the (thalamic located lesion and 22 months in the second case with the (brain stem located lesion. Conclusion Gamma knife surgery represents an alternate tool in the treatment of recurrent and/or small postoperative residual pilocytic astrocytoma especially if they are critically located

  4. Gemistocytic astrocytoma in the spinal cord in a dog: a case report

    Directory of Open Access Journals (Sweden)

    R.O. Chaves

    2016-08-01

    Full Text Available ABSTRACT This paper reports a case of a rare variant of the cervical spinal cord astrocytoma diagnosed in a dog with progressive neurological signs, initially asymmetrical, not ambulatory tetraparesis, segmental reflexes and normal muscle tone in all four limbs and absence of pain upon palpation of the cervical spine. Myelography revealed attenuation of the ventral and dorsal contrast line in the third region of the fifth cervical vertebra. At necropsy intramedullary cylindrical mass that stretched from the third to the sixth cervical vertebra, which replaced all the gray matter of the spinal cord was observed. In the histological study, there was the replacement of the substance by neoplastic cells mantle arranged loosely. The cells were large and slightly rounded. The eosinophilic cytoplasm was well defined, sometimes forming processes interconnecting cells. The nucleus was eccentric, round, oval or kidney-shaped, and the nucleolus was evident. Thus, the microscopic changes observed in the cervical spinal cord were consistent with gemistocytic astrocytoma.

  5. Mixed granular cell astrocytoma and fibrosarcoma of the brain: a case report.

    Science.gov (United States)

    Yao, Kun; Wang, Haixiang; Duan, Zejun; Bian, Yu; Xia, Lei; Ma, Zhong; Qi, Xueling

    2014-01-01

    We describe a rare primary mixed granular cell astrocytoma and fibrosarcoma neoplasm, occurring in a 52-year-old female, with morphologic, immunohistochemical and molecular genetic features, whose tumor was entirely composed of granular cells and fibrosarcoma competent. This represents, to the best of our knowledge, the first report of the mixed granular cell astrocytoma and fibrosarcoma neoplasm. Moreover, two parts forming a complex arrangement that excluded it being assessed as a coincidental collision tumor. We discuss the relationship of two parts of this rare tumor by fluorescence in situ hybridization (FISH). Sarcomatous components in this tumor had the same aberrations of chromosomes to the gliomatous components of neoplasms, consisting of 1p 19q loss and no evidence of PTEN allele loss and amplification of EGFR. It was suggested that the sarcomatous component may be derived from glioma cells i this case.

  6. Supratentorial juvenile pilocytic astrocytoma in a young adult with Silver-Russell syndrome.

    LENUS (Irish Health Repository)

    Fenton, E

    2008-12-01

    Silver-Russell syndrome is a rare genetically heterogeneous disorder in which patients demonstrate intrauterine and postnatal growth retardation, triangular facies, excessive sweating during early childhood, late closure of the anterior fontanelle and skeletal asymmetry. An association with malignancy exists and only one previous intracranial tumour has been reported, a craniopharyngioma. We report the first case of Silver-Russell syndrome associated with a supratentorial juvenile pilocytic astrocytoma.

  7. Tumor Grade versus Expression of Invasion-Related Molecules in Astrocytoma.

    Science.gov (United States)

    Virga, József; Bognár, László; Hortobágyi, Tibor; Zahuczky, Gábor; Csősz, Éva; Kalló, Gergő; Tóth, Judit; Hutóczki, Gábor; Reményi-Puskár, Judit; Steiner, László; Klekner, Almos

    2018-01-01

    Peritumoral infiltration is characteristic of astrocytomas even in low-grade tumors. Tumor cells migrate to neighbouring tissue and cause recurrence. The extracellular matrix (ECM) plays a role in tumor invasion; expression levels of its components' have been linked to tumor invasion. This study determines the mRNA and protein expression of 20 invasion-related ECM components by examining non-tumor brain; grade I-II-III astrocytoma and glioblastoma samples. Expression levels were measured by QRT-PCR and mass-spectroscopy. The connection between the expression pattern and tumor grade is statistically analyzed. During the analysis of data, key molecules (brevican, cadherin-12, fibronectin and integrin-β1) correlating the most with tumor grade were selected. While the mRNA level of brevican, ErbB2, fibronectin, integrin-β1 and versican discriminates low-grade from high-grade gliomas, of proteins RHAMM, integrin-α1 and MMP2 seems important. The expression pattern was found to be distinctive for tumor grade, as statistical classifiers are capable of identifying an unknown sample's grade using them. Furthermore, normal brain and glioma expression patterns, along with low-grade astrocytoma and glioblastoma samples, differ the most. Determining the invasion-related molecules' expression profile provides extra information regarding the tumor's clinical behavior. Additionally, identifying molecules playing a key role in glioma invasion could uncover potential therapeutic targets in the future.

  8. MicroRNA-132 targets PEA-15 and suppresses the progression of astrocytoma in vitro.

    Science.gov (United States)

    Geng, Fei; Wu, Jian-Lin; Lu, Gui-Feng; Liang, Zhi-Ping; Duan, Zhuo-Li; Gu, Xi

    2016-09-01

    Gliomas are highly malignant tumors, the most common of which are astrocytomas. A growing number of studies suggest that dysregulation of miRNAs is a frequent event contributing to the pathogenesis of gliomas. In this study, we found that over-expression of miR-132 inhibited cell proliferation and migration and triggered apoptosis, while knockdown of miR-132 showed opposite effects. PEA-15 was identified as a direct target of miR-132. Reintroduction of PEA-15 without 3'UTR region reversed the inhibitory effects of miR-132 on cell proliferation, migration, and apoptosis. MiR-132 was inversely correlated with the PEA-15 expression. CREB (cAMP response element binding protein) and KLF (Krüppel-like factor 8) were conformed as transcription factors of miR-132, which bidirectionally regulate the expression of miR-132. Our study suggests that miR-132 is an important tumor suppressor of astrocytoma progression by targeting PEA-15, while CREB and KLF can modulate the expression of miR-132, thus providing new insight into the molecular mechanisms underlying astrocytoma progression in vitro.

  9. Expression signatures of DNA repair genes correlate with survival prognosis of astrocytoma patients.

    Science.gov (United States)

    de Sousa, Juliana Ferreira; Torrieri, Raul; Serafim, Rodolfo Bortolozo; Di Cristofaro, Luis Fernando Macedo; Escanfella, Fábio Dalbon; Ribeiro, Rodrigo; Zanette, Dalila Lucíola; Paçó-Larson, Maria Luisa; da Silva, Wilson Araujo; Tirapelli, Daniela Pretti da Cunha; Neder, Luciano; Carlotti, Carlos Gilberto; Valente, Valeria

    2017-04-01

    Astrocytomas are the most common primary brain tumors. They are very resistant to therapies and usually progress rapidly to high-grade lesions. Here, we investigated the potential role of DNA repair genes in astrocytoma progression and resistance. To this aim, we performed a polymerase chain reaction array-based analysis focused on DNA repair genes and searched for correlations between expression patters and survival prognoses. We found 19 genes significantly altered. Combining these genes in all possible arrangements, we found 421 expression signatures strongly associated with poor survival. Importantly, five genes (DDB2, EXO1, NEIL3, BRCA2, and BRIP1) were independently correlated with worse prognoses, revealing single-gene signatures. Moreover, silencing of EXO1, which is remarkably overexpressed, promoted faster restoration of double-strand breaks, while NEIL3 knockdown, also highly overexpressed, caused an increment in DNA damage and cell death after irradiation of glioblastoma cells. These results disclose the importance of DNA repair pathways for the maintenance of genomic stability of high-grade astrocytomas and suggest that EXO1 and NEIL3 overexpression confers more efficiency for double-strand break repair and resistance to reactive oxygen species, respectively. Thereby, we highlight these two genes as potentially related with tumor aggressiveness and promising candidates as novel therapeutic targets.

  10. Fragile X mental retardation protein promotes astrocytoma proliferation via the MEK/ERK signaling pathway

    Science.gov (United States)

    Zhang, Hui; Hao, Zhuofang; Long, Yuesheng; Chen, Shengqiang; Su, Hang; Yuan, Zhongmin; Xu, Meng; Chen, Jingqi

    2016-01-01

    Objective To examine the association between fragile X mental retardation protein (FMRP) expression and astrocytoma characteristics. Methods Pathologic grade and expressions of glial fibrillary acidic protein (GFAP), Ki67 (proliferation marker), and FMRP were determined in astrocytoma specimens from 74 patients. Kaplan-Meier survival analysis was undertaken. Pathologic grade and protein levels of FMRP were determined in 24 additional patients with astrocytoma and 6 controls (cerebral trauma). In cultured U251 and U87 cell lines, the effects of FMRP knock-down on cell proliferation, AKT/mTOR/GSK-3β and MEK/ERK signaling were studied. The effects of FMRP knock-down on the volumes and weights of U251 cell-derived orthotopic tumors in mice were investigated. Results In patients, FMRP expression was increased in grade IV (5.1-fold, Pastrocytoma, compared with controls. FMRP and Ki67 expressions were positively correlated (R2=0.877, P30 (Pastrocytoma cell lines, FMRP knock-down slowed proliferation (Pastrocytoma may promote proliferation through activation of MEK/ERK signaling. PMID:27683117

  11. A Biobehavioral Perspective on Depressive Symptoms in Patients with a Cerebral Astrocytoma

    Science.gov (United States)

    Starkweather, Angela; Sherwood, Paula; Lyon, Debra E.; McCain, Nancy L.; Bovbjerg, Dana Howard; Broaddus, William C.

    2013-01-01

    Over 51,000 individuals are diagnosed with a primary brain tumor in the United States each year, and for those with the most common type of malignant tumor, an astrocytoma, almost 75% will die within five years of diagnosis. While surgery, radiation, and chemotherapy have improved length of survival, mortality remains high, which underscores the need to understand how other factors affect the disease trajectory. Several recent studies have shown that depressive symptoms are independently associated with reduced quality of life and survival time after controlling for medial variables in patients with an astrocytoma. Thus, depressive symptoms represent a significant risk factor for adverse outcomes in this patient population. A growing body of evidence indicates that depressive symptoms are linked to underlying biological phenomena, particularly inflammatory activation modulated through increased peripheral levels of proinflammatory cytokines. Recent research has shown that neoplastic astrocytes respond to elevated proinflammatory cytokine levels by secreting immune mediators within the central nervous system, including cytokines and glial fibrillary acidic protein (GFAP) that promote astrogliosis and angiogenesis, and may increase tumor growth and metastasis. However, because these biological factors have not as yet been measured in conjunction with depressive symptoms in these patients, little is known about the interactions that potentially influence the treatment trajectory. In order to guide future research and provide a deeper understanding of the factors that may influence depressive symptoms and length of survival in patients with an astrocytoma, a review of the literature was undertaken. Publications over the past ten years were analyzed to examine the theoretical models and measures of depressive symptoms used in previous research. While numerous studies have documented the relationship between depression and reduced length of survival, there were several

  12. Primary ciliogenesis defects are associated with human astrocytoma/glioblastoma cells

    Directory of Open Access Journals (Sweden)

    Rattner Jerome B

    2009-12-01

    Full Text Available Abstract Background Primary cilia are non-motile sensory cytoplasmic organelles that have been implicated in signal transduction, cell to cell communication, left and right pattern embryonic development, sensation of fluid flow, regulation of calcium levels, mechanosensation, growth factor signaling and cell cycle progression. Defects in the formation and/or function of these structures underlie a variety of human diseases such as Alström, Bardet-Biedl, Joubert, Meckel-Gruber and oral-facial-digital type 1 syndromes. The expression and function of primary cilia in cancer cells has now become a focus of attention but has not been studied in astrocytomas/glioblastomas. To begin to address this issue, we compared the structure and expression of primary cilia in a normal human astrocyte cell line with five human astrocytoma/glioblastoma cell lines. Methods Cultured normal human astrocytes and five human astrocytoma/glioblastoma cell lines were examined for primary cilia expression and structure using indirect immunofluorescence and electron microscopy. Monospecific antibodies were used to detect primary cilia and map the relationship between the primary cilia region and sites of endocytosis. Results We show that expression of primary cilia in normal astrocytes is cell cycle related and the primary cilium extends through the cell within a unique structure which we show to be a site of endocytosis. Importantly, we document that in each of the five astrocytoma/glioblastoma cell lines fully formed primary cilia are either expressed at a very low level, are completely absent or have aberrant forms, due to incomplete ciliogenesis. Conclusions The recent discovery of the importance of primary cilia in a variety of cell functions raises the possibility that this structure may have a role in a variety of cancers. Our finding that the formation of the primary cilium is disrupted in cells derived from astrocytoma/glioblastoma tumors provides the first

  13. Loss of inhibitor of growth (ING-4) is implicated in the pathogenesis and progression of human astrocytomas.

    Science.gov (United States)

    Klironomos, George; Bravou, Vasiliki; Papachristou, Dionysios J; Gatzounis, George; Varakis, John; Parassi, Ekaterini; Repanti, Maria; Papadaki, Helen

    2010-03-01

    Inhibitor of growth 4 (ING-4) is a tumor suppressor gene that interacts with nuclear factor-kappaB (NF-kappaB) and represses its transcriptional activity. Several lines of evidence suggest that the tumor suppressor gene ING-4, the transcription factor NF-kappaB and its target genes matrix metalloproteases MMP-2, MMP-9 and urokinase plasminogen activator (u-PA) are critically involved in tumor invasion. The aim of the present study was to investigate immunohistochemically the expression pattern of ING-4, NF-kappaB and the NF-kappaB downstream targets MMP-2, MMP-9 and u-PA in human astrocytomas from 101 patients. We found that ING-4 expression was significantly decreased in astrocytomas, and ING-4 loss was associated with tumor grade progression. Expression of p65, a NF-kappaB subunit, was significantly higher in grade IV than in grade III and grade I/II tumors, and a statistical significant negative correlation between expression of ING-4 and expression of nuclear p65 was noticed. MMP-9, MMP-2 and u-PA were overexpressed in human astrocytomas. Of note, astrocytomas of advanced histologic grades (grade III, IV) displayed significantly higher expression levels of these proteins compared to tumors of lower grades (grade I, II). Collectively, our data suggest an essential role for ING-4 in human astrocytoma development and progression possibly through regulation of the NF-kappaB-dependent expression of genes involved in tumor invasion.

  14. Combination of AQP1 and β-catenin expression is an independent prognosis factor in astrocytoma patients

    Science.gov (United States)

    Zhang, Huikun; Qin, Fengxia; Yang, Limin; He, Jia; Liu, Xiaoli; Shao, Ying; Guo, Zhifang; Zhang, Ming; Li, Wenliang; Fu, Li; Gu, Feng; Ma, Yongjie

    2017-01-01

    Previous research usually focused on single protein or gene in tumor development, actually highly heterogeneous nature and different signaling pathways largely contribute to tumor progression and tumor patients’ outcomes. Therefore, using combinatorial biomarkers to evaluate the prognostic features and guide management is gradually accepted and urgently needed. β-catenin is a well-known crucial factor in astrocytoma progression and it is involved in aquaporin1 (AQP1) mediated cell migration. In this study, we revealed the function of AQP1 in astrocytoma progression and provided the first clinical evidence that AQP1 expression was positively correlated with β-catenin. Furthermore, we proved the functional role of AQP1/β-catenin pathway in astrocytoma progression. More importantly, we discovered that combination of AQP1 and β-catenin expression was an independent prognosis factor for astrocytoma patients and it was a better survival predictor than either AQP1 or β-catenin alone. In conclusion, our study provided a novel more precise prognostication for predicting astrocytoma prognosis based on combinatorial analysis of AQP1 and β-catenin expression. PMID:29245912

  15. IDH mutant diffuse and anaplastic astrocytomas have similar age at presentation and little difference in survival: a grading problem for WHO

    NARCIS (Netherlands)

    Reuss, D.E.; Mamatjan, Y.; Schrimpf, D.; Capper, D.; Hovestadt, V.; Kratz, A.; Sahm, F.; Koelsche, C.; Korshunov, A.; Olar, A.; Hartmann, C.; Reijneveld, J.C.; Wesseling, P.; Unterberg, A.; Platten, M.; Wick, W.; Herold-Mende, C.; Aldape, K.; Deimling, A. von

    2015-01-01

    The WHO 2007 classification of tumors of the CNS distinguishes between diffuse astrocytoma WHO grade II (A IIWHO2007) and anaplastic astrocytoma WHO grade III (AA III WHO2007). Patients with A II WHO2007 are significantly younger and survive significantly longer than those with AA III WHO2007. So

  16. IDH mutant diffuse and anaplastic astrocytomas have similar age at presentation and little difference in survival : a grading problem for WHO

    NARCIS (Netherlands)

    Reuss, David E.; Mamatjan, Yasin; Schrimpf, Daniel; Capper, David; Hovestadt, Volker; Kratz, Annekathrin; Sahm, Felix; Koelsche, Christian; Korshunov, Andrey; Olar, Adriana; Hartmann, Christian; Reijneveld, Jaap C.; Wesseling, Pieter|info:eu-repo/dai/nl/157872866; Unterberg, Andreas; Platten, Michael; Wick, Wolfgang; Herold-Mende, Christel; Aldape, Kenneth; von Deimling, Andreas

    2015-01-01

    The WHO 2007 classification of tumors of the CNS distinguishes between diffuse astrocytoma WHO grade II (A IIWHO2007) and anaplastic astrocytoma WHO grade III (AA IIIWHO2007). Patients with A IIWHO2007 are significantly younger and survive significantly longer than those with AA IIIWHO2007. So far,

  17. Report of effective trametinib therapy in 2 children with progressive hypothalamic optic pathway pilocytic astrocytoma: documentation of volumetric response.

    Science.gov (United States)

    Miller, Catherine; Guillaume, Daniel; Dusenbery, Kathryn; Clark, H Brent; Moertel, Christopher

    2017-03-01

    Brain tumors are the most common solid tumor in childhood, and astrocytomas account for the largest proportion of these tumors. Increasing sophistication in genetic testing has allowed for the detection of specific mutations within tumor subtypes that may represent targets for individualized tumor treatment. The mitogen-activating protein kinase (MAPK) pathway and, more specifically, BRAF mutations have been shown to be prevalent in pediatric pilocytic astrocytomas and may represent one such area to target. Herein, the authors describe 2 cases of inoperable, chemotherapy-resistant pediatric pilocytic astrocytomas with a documented response to trametinib, an MAPK pathway inhibitor. While these cases were not treated in the setting of a clinical trial, their data support further ongoing clinical trial investigation to evaluate the safety and efficacy of this agent in pediatric low-grade gliomas.

  18. The expression level of CB1 and CB2 receptors determines their efficacy at inducing apoptosis in astrocytomas.

    Directory of Open Access Journals (Sweden)

    Eiron Cudaback

    2010-01-01

    Full Text Available Cannabinoids represent unique compounds for treating tumors, including astrocytomas. Whether CB(1 and CB(2 receptors mediate this therapeutic effect is unclear.We generated astrocytoma subclones that express set levels of CB(1 and CB(2, and found that cannabinoids induce apoptosis only in cells expressing low levels of receptors that couple to ERK1/2. In contrast, cannabinoids do not induce apoptosis in cells expressing high levels of receptors because these now also couple to the prosurvival signal AKT. Remarkably, cannabinoids applied at high concentration induce apoptosis in all subclones independently of CB(1, CB(2 and AKT, but still through a mechanism involving ERK1/2.The high expression level of CB(1 and CB(2 receptors commonly found in malignant astrocytomas precludes the use of cannabinoids as therapeutics, unless AKT is concomitantly inhibited, or cannabinoids are applied at concentrations that bypass CB(1 and CB(2 receptors, yet still activate ERK1/2.

  19. Relationship Between Cytogenetic Complexity and Peritumoral Edema in High-Grade Astrocytoma.

    Science.gov (United States)

    Jeong, Kyung Ho; Song, Young Jin; Han, Jin Yeong; Kim, Ki Uk

    2016-11-01

    The purpose of the study is to reveal the association of cytogenetic compltyexi and peritumoral edema volume (PTEV) and its prognostic significance in high-grade astrocytoma patients by culturing patient tumor cells. Twenty-seven high-grade astrocytoma patients were divided into three groups according to karyotype complexity: normal, non-complex karyotype (NCK), and complex karyotype (CK). Endothelial growth factor receptor (EGFR) amplification was detected by FISH, and its association with chromosome 7 abnormalities was analyzed. Mean PTEV of each group was compared by ANOVA to evaluate the relationship between PTEV and cytogenetic complexity. The PTEV of patients in normal (n=6), NCK (n=8), and CK (n=13) groups were 24.52±17.73, 34.26±35.04, and 86.31±48.7 cm³, respectively (P=0.005). Ten out of 11 patients with EGFR amplification showed abnormalities in chromosome 7. The mean PTEV of EGFR-amplified and non-amplified groups were 80.4±53.7 and 41.3±37.9 cm³, respectively (P=0.035). The average survival of patients with PTEV less than 90 cm³ was 30.52±26.11 months, while in patients with PTEVs over or equal to 90 cm³, it was 10.83±5.53 months (P=0.007). The results show an association of complex karyotype with the PTEV of high-grade astrocytoma. EGFR amplification plays a significant role in the formation of peritumoral edema, causing PTEV to increase, which is related with survival. This implies that cytogenetic karyotype can be applied as a prognostic factor.

  20. The emerging role of m-TOR up-regulation in brain Astrocytoma.

    Science.gov (United States)

    Ryskalin, Larisa; Limanaqi, Fiona; Biagioni, Francesca; Frati, Alessandro; Esposito, Vincenzo; Calierno, Maria Teresa; Lenzi, Paola; Fornai, Francesco

    2017-05-01

    The present manuscript is an overview of various effects of mTOR up-regulation in astrocytoma with an emphasis on its deleterious effects on the proliferation of Glioblastoma Multiforme. The manuscript reports consistent evidence indicating the occurrence of mTOR up-regulation both in experimental and human astrocytoma. The grading of human astrocytoma is discussed in relationship with mTOR up-regulation. In the second part of the manuscript, the biochemical pathways under the influence of mTOR are translated to cell phenotypes which are generated by mTOR up-regulation and reverted by its inhibition. A special section is dedicated to the prominent role of autophagy in mediating the effects of mTOR in glioblastoma. In detail, autophagy inhibition produced by mTOR up-regulation determines the fate of cancer stem cells. On the other hand, biochemical findings disclose the remarkable effects of autophagy activators as powerful inducers of cell differentiation with a strong prevalence towards neuronal phenotypes. Thus, mTOR modulation acts on the neurobiology of glioblastoma just like it operates in vivo at the level of brain stem cell niches by altering autophagy-dependent cell differentiation. In the light of such a critical role of autophagy we analyzed the ubiquitin proteasome system. The merging between autophagy and proteasome generates a novel organelle, named autophagoproteasome which is strongly induced by mTOR inhibitors in glioblastoma cells. Remarkably, when mTOR is maximally inhibited the proteasome component selectively moves within autophagy vacuoles, thus making the proteasome activity dependent on the entry within autophagy compartment.

  1. Heterogeneity of histopathological presentation of pilocytic astrocytoma - diagnostic pitfalls. A review.

    Science.gov (United States)

    Matyja, E; Grajkowska, W; Stępień, K; Naganska, E

    2016-01-01

    Pilocytic astrocytomas (PAs) are the most frequent primary astroglial tumours affecting children and adolescents. They occur sporadically or in association with a genetically determined syndrome - neurofibromatosis type 1. Classic PA usually manifests as a well-circumscribed, often cystic, slowly growing tumour, which corresponds to WHO grade I. The majority of pilocytic tumours arise along the neuraxis, predominantly in the cerebellum. They are associated with favourable long-term outcome or spontaneous regression, even after incomplete resection. However, the behaviour and prognosis might also be related to tumour histology and location. Pilomyxoid astrocytoma (PMA) represents a variant of classical PA with more invasive growth and increased risk of recurrences and dissemination. Typically, PAs exhibit distinct histology with biphasic architecture of loose, microcystic and compact, fibrillary areas. However, some tumours arise in an uncommon location and display heterogeneous histopathological appearance. The morphological pattern of PA can mimic some other glial neoplasms, including oligodendroglioma, pleomorphic xanthoastrocytoma, ependymoma or diffuse astrocytoma. Not infrequently, the advanced degenerative changes, including vascular fibrosis, and recent and old haemorrhages, may mimic vascular pathology. Sometimes, the neoplastic piloid tissue can resemble reactive gliosis, related to long-standing non neoplastic lesions. Not infrequently, PA exhibits histological features typical for anaplasia, including necrosis, mitoses and glomeruloid vascular proliferation that can suggest a diffuse high-grade glioma. However, even those PAs that lack distinct histological features of anaplasia can behave unpredictably, in a more aggressive manner, with leptomeningeal spreading. Genetic alterations resulting in aberrant signalling of the mitogen-activated protein kinase (MAPK) pathway have been considered to underlie the development of PAs. The most commonly identified

  2. Adult anaplastic pilocytic astrocytoma - a diagnostic challenge? A case series and literature review.

    Science.gov (United States)

    Fiechter, Michael; Hewer, Ekkehard; Knecht, Urspeter; Wiest, Roland; Beck, Jürgen; Raabe, Andreas; Oertel, Markus F

    2016-08-01

    Anaplastic pilocytic astrocytoma (APA) is an exceptionally rare type of high-grade glioma in adults. Establishing histopathological diagnosis is challenging and its clinical and radiological appearance insidious. By this case series and first literature review we investigated the various clinical, neuroradiological, and histopathological features of APA in adults. An in hospital screening of the database from the Institute of Pathology was conducted to identify cases of APA. Further, we performed a literature review in PubMed using the keywords "anaplastic/malignant/atypical AND pilocytic astrocytoma" and "anaplastic astrocytoma/glioblastoma AND Rosenthal fibers" and summarized the current knowledge about APA in adults. Over the last decade we were able to identify 3 adult patients with APA in our hospital. According to the pertinent literature, the prognosis of APA in adults (documented survival of up to 10 years) appears to be better than in other high-grade gliomas. Few cases were associated with neurofibromatosis type 1, which seems to predispose for development of APA. Although molecular genetics is still of limited value for differentiation of APA from other high-grade glioma, advanced neuroimaging techniques such as magnetic resonance perfusion imaging and spectroscopy allow improved differential work-up. In particular, APA in adults has the ability to mimic various neurological diseases such as tumefactive demyelinating lesions, low-, or high-grade gliomas. Although currently not explicitly recognized as a distinct clinico-pathologic entity it seems that adult APA behaves differently from conventional high-grade glioma and should be included in differential diagnostics to enable adequate patient care. However, further studies are needed to better understand this extremely rare disease. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  3. Promotion of astrocytoma cell invasion by micro RNA-22 targeting of tissue inhibitor of matrix metalloproteinase-2.

    Science.gov (United States)

    Ohnishi, Yu-Ichiro; Iwatsuki, Koichi; Ishihara, Masahiro; Ohkawa, Toshika; Kinoshita, Manabu; Shinzawa, Koei; Fujimoto, Yasunori; Yoshimine, Toshiki

    2017-03-01

    OBJECTIVE Diffuse astrocytomas (DAs) have a high recurrence rate due to diffuse infiltration into the brain and spinal cord. Micro RNAs (miRNAs) are small noncoding RNAs that regulate gene expression by binding to complementary sequences of target messenger RNA (mRNA). It has been reported that miRNA-22 (miR-22) is involved in the invasion of some cancer cell lines. The aim of this study was to identify the biological effects of miR-22 in regard to the invasion of human DAs. METHODS The authors evaluated whether the level of miR-22 is elevated in human spinal DAs by using miRNA chips. Next, the role of miR-22 in 1321N1 human astrocytoma cells was investigated. Finally, to elucidate whether miR-22 promotes invasion by astrocytoma cells in vivo, the authors transplanted miR-22 overexpressed astrocytoma cells into mouse thoracic spinal cord. RESULTS The miR-22 significantly upregulated the invasion capacity of 1321N1 cells. Computational in silico analysis predicted that tissue inhibitor of matrix metalloproteinase-2 (TIMP2) is a target gene of miR-22. This was confirmed by quantitative reverse transcription polymerase chain reaction and Western blotting, which showed that miR-22 inhibited TIMP2 mRNA and protein expression, respectively. Luciferase reporter assays demonstrated that miR-22 directly bound the 3'-untranslated regions of TIMP2. The authors further showed that miR-22 promoted invasiveness in 1321N1 astrocytoma cells when transplanted into mouse spinal cord. CONCLUSIONS These data suggest that miR-22 acts to regulate invasion of 1321N1 astrocytoma cells by targeting TIMP2 expression. Additional studies with more cases and cell lines are required to elucidate the findings of this study for a novel treatment target for spinal DAs.

  4. Extracranial bone metastases from recurrent anaplastic astrocytoma on FDG PET/CT: A case report a care-compliant article.

    Science.gov (United States)

    Li, Zu-Gui; Mu, Hai-Yu

    2017-06-01

    Extracranial bone metastases from astrocytoma are rare and frequently detected as part of multiorgan metastases. It is extremely rare for astrocytoma to have extracranial bone metastases alone. The importance of whole-body fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) imaging in evaluating extracranial metastasis (ECMs) has not been described effectively due to the rarity of this event. The purpose of our case report is to emphasize the role of FDG PET/CT in the assessment of tumor recurrence and extracranial bone metastases from anaplastic astrocytoma. A 25-year-old woman was firstly admitted with a 4-month history of progressive blurred vision, and 2-month history of intermittent headache. Presurgical MRI imaging revealed a large mass in the left trigone of lateral ventricle. Subsequently, she underwent tumor resection, radiotherapy and chemotherapy. A final pathological diagnosis of anaplastic astrocytoma (WHO III) was made. Nearly 12 months after the surgery, the follow-up brain MR imaging revealed a contrast-enhanced lesion in the site of operative region. Whole-body FDG PET/CT imaging was performed to evaluate the situation. Postoperative brain FDG PET/CT showed an abnormal focal FDG uptake corresponding to the contrast-enhanced lesion in the operative area, suggesting a tumor recurrence. Whole-body FDG PET/CT also showed multiple FDG-avid osteosclerotic lesions in the body. It was highly suggestive of extracranial bone metastases. A subsequent open bone biopsy of FDG-avid lesion in right iliac crest was performed. Histopathological and immunohistochemical findings indicated characteristic of glioma. The patient died 1 month later, nearly 13 months after the initial diagnosis. ECMs from anaplastic astrocytoma are extremely rare but they do occur. Whole-body FDG PET/CT imaging with inclusion of brain was valuable in differentiating tumor recurrence from radiation necrosis and in detecting uncommon extracranial bone metastases

  5. Longitudinal mutational analysis of a cerebellar pilocytic astrocytoma recurring as a ganglioglioma.

    Science.gov (United States)

    Fiset, Pierre O; Fontebasso, Adam M; De Jay, Nicolas; Gayden, Tenzin; Nikbakht, Hamid; Majewski, Jacek; Jabado, Nada; Albrecht, Steffen

    2017-02-01

    A cerebellar pilocytic astrocytoma (PA) in a child recurred first with a PA histology and then with features of a ganglioglioma (GG). Molecular genetic analyses of the tumors confirmed a BRAF V600E mutation in all. They also all harbored a T202M mutation in ERK1, a kinase downstream of BRAF that is implicated in glial versus neuronal differentiation. The GG sample contained several variants that were not present in the PA samples; in particular, it had a truncating mutation in MAP2. These findings not only underscore the role of BRAF as oncogenic driver but also suggest that other genes may influence tumor morphology. © 2016 Wiley Periodicals, Inc.

  6. A case report on paraneoplastic encephalitis associated with astrocytoma - An unknown entity

    Directory of Open Access Journals (Sweden)

    Yogeshwari S Deshmukh

    2016-01-01

    Full Text Available Paraneoplastic encephalitis is a multifocal inflammatory disorder of the central nervous system (CNS that is associated with remote neoplasias. The most common malignancy associated with it is bronchial carcinoma, typically small cell carcinoma of lung. It has never been described in association with intracranial neoplasm. We present and discuss the clinical, radiological, and histopathological findings of paraneoplastic encephalitis with intracranial space-occupying lesions (SOLs in a 55-year-old man. He was thoroughly investigated and biopsy revealed presence of astrocytoma with changes of paraneoplastic encephalitis.

  7. IDH1 mutated low grade astrocytoma occurring in MSH2 mutated Lynch syndrome family

    Directory of Open Access Journals (Sweden)

    Alaa Alkhotani

    2016-12-01

    Full Text Available Lynch syndrome (LS is an autosomal dominant tumour predisposition syndrome caused by a germline mutation in one of the DNA mismatch repair (MMR genes.Patients with these mutations have an increased risk of brain tumours, the vast majority of which are glioblastomas and medulloblastomas, and their occurrence has been termed Turcot Syndrome. The case presented herein of a member of a Lynch syndrome family with an MSH2 mutation expands the spectrum of brain tumours occurring in Lynch syndrome to include low grade astrocytomas, and is the first reported case of an IDH1 (R132H mutated brain tumour occurring in a Lynch syndrome family.

  8. Differential prefrontal-like deficit in children after cerebellar astrocytoma and medulloblastoma tumor

    Directory of Open Access Journals (Sweden)

    Quintero Eliana A

    2008-04-01

    Full Text Available Abstract Background This study was realized thanks to the collaboration of children and adolescents who had been resected from cerebellar tumors. The medulloblastoma group (CE+, n = 7 in addition to surgery received radiation and chemotherapy. The astrocytoma group (CE, n = 13 did not receive additional treatments. Each clinical group was compared in their executive functioning with a paired control group (n = 12. The performances of the clinical groups with respect to controls were compared considering the tumor's localization (vermis or hemisphere and the affectation (or not of the dentate nucleus. Executive variables were correlated with the age at surgery, the time between surgery-evaluation and the resected volume. Methods The executive functioning was assessed by means of WCST, Complex Rey Figure, Controlled Oral Word Association Test (letter and animal categories, Digits span (WISC-R verbal scale and Stroop test. These tests are very sensitive to dorsolateral PFC and/or to medial frontal cortex functions. The scores for the non-verbal Raven IQ were also obtained. Direct scores were corrected by age and transformed in standard scores using normative data. The neuropsychological evaluation was made at 3.25 (SD = 2.74 years from surgery in CE group and at 6.47 (SD = 2.77 in CE+ group. Results The Medulloblastoma group showed severe executive deficit (≤ 1.5 SD below normal mean in all assessed tests, the most severe occurring in vermal patients. The Astrocytoma group also showed executive deficits in digits span, semantic fluency (animal category and moderate to slight deficit in Stroop (word and colour tests. In the astrocytoma group, the tumor's localization and dentate affectation showed different profile and level of impairment: moderate to slight for vermal and hemispheric patients respectively. The resected volume, age at surgery and the time between surgery-evaluation correlated with some neuropsychological executive variables

  9. Spontaneous intratumoural and intraventricular haemorrhage associated with a pilomyxoid astrocytoma in the hypothalamic/chiasmatic region.

    Science.gov (United States)

    Wang, Zhe; Yan, Hong-Mei; Zhou, Xiu-Rong; Liu, Jin-Kai; Chang, Jian-Yong; Wang, Yu-Ting

    2016-11-01

    Pilomyxoid astrocytoma (PMA) is a rare, low-grade glioma that is recognised as a variant of pilocytic astrocytoma. There have been few reports on this pathologic entity presenting with spontaneous haemorrhage. In this study, we report a rare case of PMA in the hypothalamic/chiasmatic region presenting with intratumoural and intraventricular haemorrhage. An external ventricular drain was urgently inserted. A ventriculo-peritoneal shunt (VP) was undergone 4weeks thereafter. The patient received fractionated Gamma Knife radiosurgery in another hospital 3weeks after the VP shunt. Three months later, subtotal resection of the tumour was performed in our hospital via a pterional approach. The pathological diagnosis was PMA. Postoperatively, no adjuvant therapy was given, and the neurologic deficits were improved. However, the presentation of endocrine deficits remained. Notably, PMAs in the hypothalamic/chiasmatic region presenting with massive intratumoural and intraventricular haemorrhage may result in a severe condition and long-term impairment of endocrine function. Long-term follow-up is required to monitor the recurrence of the tumour and endocrinopathy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Malignant transformation of diffuse astrocytoma to glioblastoma associated with newly developed BRAF V600E mutation.

    Science.gov (United States)

    Kanamori, Masayuki; Suzuki, Hiroyoshi; Takei, Hidehiro; Sonoda, Yukihiko; Uenohara, Hiroshi; Tominaga, Teiji

    2016-01-01

    A 29-year-old man presented with scintillation scotoma. MR imaging demonstrated a diffuse lesion in right parahippocampal gyrus. He underwent a biopsy, and the diagnosis was diffuse astrocytoma. Because of enlargement and new areas of gadolinium enhancement, the tumor was resected 18 months after biopsy. Histological examination revealed malignant transformation to glioblastoma with small areas of epithelioid component. He received radiation and temozolomide chemotherapy. Local recurrence was found 20 months after first resection. He underwent second resection, and the diagnosis was glioblastoma. DNA from the micro-dissected paraffin-embedded sections were analyzed for the mutation of the isocitrate dehydrogenase1 (IDH1) and IDH2 and v-RAF murine sarcoma viral oncogene homolog B1 (BRAF) genes. No mutations of the IDH genes were detected in any tumor specimen. In contrast, missense mutation at codon 600 in the BRAF gene (BRAF V600E) was found exclusively in the malignant areas from both resected glioblastoma specimens. We screened other genetic aberrations commonly seen in glioblastoma with multiplex ligation-dependent probe analysis. Deletion of CDKN2A and CDKN2B loci was found both in diffuse astrocytoma and glioblastoma component, but no other significant alterations were found. This case suggests that the BRAF V600E mutation may be involved in the malignant transformation to glioblastoma.

  11. Multimodal target point assessment for stereotactic biopsy in children with diffuse bithalamic astrocytomas.

    Science.gov (United States)

    Messing-Jünger, A M; Floeth, F W; Pauleit, D; Reifenberger, G; Willing, R; Gärtner, J; Coenen, H H; Langen, K J

    2002-08-01

    Diffuse glial tumors with bithalamic involvement are rare in children. Diagnostic assessment can be difficult as the radiological findings can be unspecific. In order to enhance the diagnostic yield metabolic imaging with MRS and PET using FET ( O-(2-[(18)F]fluoroethyl)- L-tyrosine) was performed in two children (2 and 10 years of age). Co-registered images were used for image-guided biopsy, which was planned with neuronavigation and stereotaxy simultaneously. Biopsies from the right thalamus were planned, but locations were changed in both cases after metabolic imaging was available. MRS (thalamic voxel) was typical for a glial tumor in one child. In the older girl FET-PET revealed an unexpected lesion in the left cerebellar hemisphere, with a tumor-to-cortex ratio of 3.8, as against 1.7 in the thalamus. Accordingly, a stereotactic biopsy specimen was taken from the left cerebellar hemisphere, and a final diagnosis of anaplastic astrocytoma was made. The other patient showed a higher uptake (tumor-to-cortex ratio 1.6) in the left dorsal thalamus, compared with bilateral homogeneous hyperintensity of the thalamus structures on MRI. Stereotactic biopsy revealed a low-grade diffuse astrocytoma. Stereotactic biopsy using metabolic imaging and image fusion can enhance the diagnostic yield in cases of diffuse pediatric gliomas disclosing unexpected 'hot spots'.

  12. Detection of novel genomic aberrations in anaplastic astrocytomas by GTG-banding, SKY, locus-specific FISH, and high density SNP-array.

    Science.gov (United States)

    Holland, Heidrun; Ahnert, Peter; Koschny, Ronald; Kirsten, Holger; Bauer, Manfred; Schober, Ralf; Meixensberger, Jürgen; Fritzsch, Dominik; Krupp, Wolfgang

    2012-06-15

    Astrocytomas represent the largest and most common subgroup of brain tumors. Anaplastic astrocytoma (WHO grade III) may arise from low-grade diffuse astrocytoma (WHO grade II) or as primary tumors without any precursor lesion. Comprehensive analyses of anaplastic astrocytomas combining both cytogenetic and molecular cytogenetic techniques are rare. Therefore, we analyzed genomic alterations of five anaplastic astrocytomas using high-density single nucleotide polymorphism arrays combined with GTG-banding and FISH-techniques. By cytogenetics, we found 169 structural chromosomal aberrations most frequently involving chromosomes 1, 2, 3, 4, 10, and 12, including two not previously described alterations, a nonreciprocal translocation t(3;11)(p12;q13), and one interstitial chromosomal deletion del(2)(q21q31). Additionally, we detected previously not documented loss of heterozygosity (LOH) without copy number changes in 4/5 anaplastic astrocytomas on chromosome regions 5q11.2, 5q22.1, 6q21, 7q21.11, 7q31.33, 8q11.22, 14q21.1, 17q21.31, and 17q22, suggesting segmental uniparental disomy (UPD), applying high-density single nucleotide polymorphism arrays. UPDs are currently considered to play an important role in the initiation and progression of different malignancies. The significance of previously not described genetic alterations in anaplastic astrocytomas presented here needs to be confirmed in a larger series. Copyright © 2012 Elsevier GmbH. All rights reserved.

  13. CASC2c as an unfavorable prognosis factor interacts with miR-101 to mediate astrocytoma tumorigenesis.

    Science.gov (United States)

    Liu, Changhong; Sun, Yingnan; She, Xiaoling; Tu, Chaofeng; Cheng, Xiping; Wang, Lin; Yu, Zhibin; Li, Peiyao; Liu, Qing; Yang, Honghui; Li, Guiyuan; Wu, Minghua

    2017-03-02

    miR-101 has been suggested as a tumor suppressor, but the promoter methylation and loss of heterozygosity didn't contribute to its low expression in astrocytoma. We investigated the role of a new long non-coding RNA CASC2c binding with miR-101. High CASC2c was positively correlated with astrocytoma progression, and an unfavorable prognosis factor for patients. Knockdown CASC2c inhibited proliferation and tumorgenesis. Overexpression of CASC2c promotes the malignant characteristic of astrocytoma cells.CASC2c directly bound miR-101 and mediated pre-miR-101 processing into mature miR-101, and functions as a competitor of miR-101 target genes such as CPEB1. Patients who possessed both low CASC2c and high miR-101 had a longer survival than those of low CASC2c alone or high miR-101 alone. In summary, CASC2c plays the onco-RNA role in the tumorgenesis of astrocytoma by acting as a decoy miR-101 sponge. Combination of low expression of CASC2c and high expression of miR-101 has an important referential significance to evaluate the prognosis of patients.

  14. Impaired RNA splicing of 5'-regulatory sequences of the astroglial glutamate transporter EAAT2 in human astrocytoma

    NARCIS (Netherlands)

    Münch, C.; Penndorf, A.; Schwalenstöcker, B.; Troost, D.; Ludolph, A. C.; Ince, P.; Meyer, T.

    2001-01-01

    A loss of the glutamate transporter EAAT2 has been reported in the neoplastic transformation of astrocytic cells and astrocytoma. The RNA expression of EAAT2 and five 5'-regulatory splice variants was investigated to identify alterations of the post-transcriptional EAAT2 gene regulation in human

  15. Cloning of a novel transcription factor-like gene amplified in human glioma including astrocytoma grade I

    NARCIS (Netherlands)

    Fischer, U.; Heckel, D.; Michel, A.; Janka, M.; Hulsebos, T.; Meese, E.

    1997-01-01

    Gene amplification, which is generally considered to occur late in tumor development, is a common feature of high grade glioma. Up until now, there have been no reports on amplification in astrocytoma grade I. In this study, we report cloning and sequencing of a cDNA termed glioma-amplified sequence

  16. Pilocytic Astrocytoma of the Optic Pathway: A Tumour Deriving from Radial Glia Cells with a Specific Gene Signature

    Science.gov (United States)

    Tchoghandjian, Aurelie; Fernandez, Carla; Colin, Carole; El Ayachi, Ikbale; Voutsinos-Porche, Brigitte; Fina, Frederic; Scavarda, Didier; Piercecchi-Marti, Marie-Dominique; Intagliata, Dominique; Ouafik, L'Houcine; Fraslon-Vanhulle, Caroline; Figarella-Branger, Dominique

    2009-01-01

    Pilocytic astrocytomas are WHO grade I gliomas that occur predominantly in childhood. They share features of both astroglial and oligodendroglial lineages. These tumours affect preferentially the cerebellum (benign clinical course) and the optic pathway, especially the hypothalamo-chiasmatic region (poor prognosis). Understanding the molecular…

  17. Hemosiderin pigmentation of tumour cells in cerebellar pilocytic astrocytoma associated with post-traumatic hemorrhage in adults.

    Science.gov (United States)

    Taraszewska, Anna; Czernicki, Zbigniew; Andrychowski, Jarosław

    2005-01-01

    The pilocytic astrocytoma is only rarely associated with gross intratumoral hemorrhage despite rich vasculature and blood vessel changes, accompanied often by perivascular depots of hemosiderin. We report an unusual case of pigmented cerebellar pilocytic astrocytoma presenting with posttraumatic hemorrhage in a 38-year-old man with no history related to the tumor. CT and MRI examination after head injury demonstrated unexpectedly the cystic lesion of 2 cm in diameter in the region of the right cerebellar hemisphere and vermis. The lesion was associated with hematoma and it was surgically removed 3 weeks after trauma. Histopathological examination revealed pilocytic astrocytoma tissue with broad hemorrhagic changes and with an unusual pattern of massive pigmentation of the cytoplasm of pilocytic astrocytes, consistent with hemosiderosis. Positive stains for iron and ferritin and ultrastructural study confirmed deposition of hemosiderin granules in the tumour cells. There was no evidence of melanin or melanosomes. This finding of hemosiderin accumulation in the cytoplasm of neoplastic astroglia seems to be analogous to post-hemorrhagic pigmentation of the normal Bergmann glia and subpial astrocytes. In the literature, the examples of neuroepithelial tumors with hemosiderin pigmentation of tumor cells have been rarely documented. To our knowledge, this is the first reported case of pigmented pilocytic astrocytoma exhibiting extensive intracellular hemosiderin deposition.

  18. A retrospective observational study on the treatment outcomes of 26 patients with spinal cord astrocytoma including two cases of malignant transformation.

    Science.gov (United States)

    Ryu, Seong Jun; Kim, Jong Yul; Kim, Kyung Hyun; Park, Jeong Yoon; Kuh, Sung Uk; Chin, Dong Kyu; Kim, Keun Su; Cho, Yong Eun; Kim, Se Hoon

    2016-12-01

    To determine the biologic behavior and prognostic factors of spinal cord astrocytoma, we reviewed surgical and clinical outcomes. Due to the rarity of spinal cord astrocytoma, there is a lack of research regarding this type of tumor and malignant transformation. We retrospectively reviewed the data from all patients on whom we performed spinal cord tumor removal between 1983 and 2014. Twenty-six patients were pathologically confirmed to have spinal cord astrocytoma or glioblastoma. Surgical extent and disease progression were confirmed by the surgeon based on operative findings, postoperative MRI, and outpatient department (OPD) follow-up. Pain or neurological deficit was the chief complaint for all patients. With MRI studies, there is a tendency for high-grade astrocytomas to show as enhanced and heterogeneous images. Two of the low-grade astrocytomas showed malignant transformation over the course of 4 and 11 months, respectively. The overall survival (OS) for low-grade astrocytoma was 28-480 months (mean 156.38 months); the OS for high-grade astrocytoma was 1-36 months (mean 12.00 months). Two of 12 low-grade cases showed malignant transformations at 4 and 11 months, respectively, based on pathological confirmation. With spinal cord astrocytomas, enhanced MRI results appeared similar to those of a malignant lesion. We suggest close observation and image correlation of low-grade astrocytomas, even when pathologically confirmed as low-grade. In this review, we found that histologic grade is the most important prognostic factor, although it is not always concordant with biologic behaviors.

  19. Eya2 overexpression promotes the invasion of human astrocytoma through the regulation of ERK/MMP9 signaling

    Science.gov (United States)

    Wen, Zhifeng; Liang, Chuansheng; Pan, Qichen; Wang, Yunjie

    2017-01-01

    The overexpression of eyes absent (Eya) 2 has been found in several human cancers. However, its biological roles and clinical significance in human astrocytoma have not yet been explored. This study investigated the clinical significance and biological roles of Eya2 in human astrocytoma tissues and cell lines. Using immunohistochemistry, we found Eya2 overexpression in 33 out of 90 (36.7%) astrocytoma specimens. The rate of Eya2 overexpression was higher in grade III–IV (48.1%) than in grade I+II astrocytomas (21.1%). Transfection with an Eya2 expression plasmid was performed in A172 cells with a low endogenous expression of Eya2 and the knockdown of Eya2 was carried out in U251 cells with a high endogenous expression using siRNA. Eya2 overexpres-sion induced A172 cell proliferation and invasion, while the knockdown of Eya2 using siRNA decreased the proliferation and invasion of U251 cells. In addition, we found that transfection with the Eya2 expression plasmid facilitated cell cycle progression, and that the knockdown of Eya2 inhibited cell cycle progression, accompanied by a change in the expression of cell cycle-related proteins, including cyclin D1 and cyclin E. Eya2 also positively regulated extracellular signal-regulated kinase (ERK) activity and matrix metalloproteinase (MMP)9 expression. The blockade of ERK signaling using an inhibitor abolished the effects of Eya2 on A172 cell invasion and MMP9 production. In addition, we found that there was a positive correlation between Eya2 and Six1 in the astrocytoma cell lines. Immunoprecipitation revealed that Eya2 interacted with Six1 protein in the U251 cell line, which exhibited a high expression of both proteins. Eya2 failed to upregulate MMP expression in the A172 cells in which Six1 was silenced. On the whole, our data indicate that Eya2 may serve as a potential oncoprotein in human astrocytoma. Eya2 regulates astrocytoma cell proliferation and invasion, possibly through the regulation of ERK signaling

  20. Drug/diet synergy for managing malignant astrocytoma in mice: 2-deoxy-D-glucose and the restricted ketogenic diet

    Directory of Open Access Journals (Sweden)

    Mukherjee Purna

    2008-11-01

    Full Text Available Abstract Background Astrocytomas are largely dependent on glycolysis to satisfy their bioenergetic requirements for growth and survival. Therapies that target glycolysis can potentially manage astrocytoma growth and progression. Dietary restriction of the high fat/low carbohydrate ketogenic diet (KD-R reduces glycolysis and is effective in managing experimental mouse and human astrocytomas. The non-metabolizable glucose analogue, 2-deoxy-D-glucose (2-DG, is a potent glycolytic inhibitor that can mimic effects of energy restriction both in vitro and in vivo, but can also produce adverse effects when administered at doses greater than 200 mg/kg. The goal here was to determine if low doses of 2-DG could act synergistically with the KD-R to better manage growth of the CT-2A malignant mouse astrocytoma. Methods The therapeutic effect of a KD-R supplemented with a low dose of 2-DG (25 mg/kg was examined in adult C57BL/6J mice bearing the syngeneic CT-2A malignant astrocytoma grown orthotopically. Mice were fed the standard unrestricted diet for the first 3 days after tumor implantation prior to their separation into one of four diet groups fed either a standard rodent diet in unrestricted amounts (SD-UR or a KD-R with or without 2-DG for 10 days. The KD-R was restricted to reduce body weight by about 20%. 2-DG was initiated 6 days after tumor implantation and was continued for 7 days. Brain tumors were excised and weighed. Results Energy intake, body weights, and CT-2A tumor weights were similar in the SD-UR and the SD-UR+2-2DG mouse groups over the dietary treatment period (days 3–13. Tumor weights were about 48% and 80% lower in the KD-R and in the KD-R+2-DG groups, respectively, than in the SD-UR group. Mouse health and vitality was better in the KD-R group than in the KD-R+2-DG group. Conclusion Astrocytoma growth was reduced more in the KD-R mouse group supplemented with 2-DG than in the mouse groups receiving either dietary restriction or 2-DG

  1. MicroRNA-124-3p regulates cell proliferation, invasion, apoptosis, and bioenergetics by targeting PIM1 in astrocytoma.

    Science.gov (United States)

    Deng, Danni; Wang, Lei; Chen, Yao; Li, Bowen; Xue, Lian; Shao, Naiyuan; Wang, Qiang; Xia, Xiwei; Yang, Yilin; Zhi, Feng

    2016-07-01

    The PIM1 protein is an important regulator of cell proliferation, the cell cycle, apoptosis, and metabolism in various human cancers. MicroRNAs (miRNAs) are powerful post-transcriptional gene regulators that function through translational repression or transcript destabilization. Therefore, we aimed to identify whether a close relationship exists between PIM1 and miRNAs. PIM1 protein levels and mRNA levels were significantly upregulated in astrocytoma tissues, indicating the oncogenic role of PIM1 in astrocytoma. Further bioinformatics analysis indicated that miR-124-3p targeted the 3'-UTR of PIM1. We also observed an inverse correlation between the miR-124-3p levels and PIM1 protein or mRNA levels in astrocytoma samples. Next, we experimentally confirmed that miR-124-3p directly recognizes the 3'-UTR of the PIM1 transcript and regulates PIM1 expression at both the protein and mRNA levels. Furthermore, we examined the biological consequences of miR-124-3p targeting PIM1 in vitro. We showed that the repression of PIM1 in astrocytoma cancer cells by miR-124-3p suppressed proliferation, invasion, and aerobic glycolysis and promoted apoptosis. We observed that the restoration or inhibition of PIM1 activity resulted in effects that were similar to those induced by miR-124-3p inhibitors or mimics in cancer cells. Finally, overexpression of PIM1 rescued the inhibitory effects of miR-124-3p. In summary, these findings aid in understanding the tumor-suppressive role of miR-124-3p in astrocytoma pathogenesis through the inhibition of PIM1 translation. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  2. Rapid progression to glioblastoma in a subset of IDH-mutated astrocytomas: a genome-wide analysis.

    Science.gov (United States)

    Richardson, Timothy E; Snuderl, Matija; Serrano, Jonathan; Karajannis, Matthias A; Heguy, Adriana; Oliver, Dwight; Raisanen, Jack M; Maher, Elizabeth A; Pan, Edward; Barnett, Samuel; Cai, Chunyu; Habib, Amyn A; Bachoo, Robert M; Hatanpaa, Kimmo J

    2017-05-01

    According to the recently updated World Health Organization (WHO) classification (2016), grade II-III astrocytomas are divided into IDH-wildtype and IDH-mutant groups, the latter being significantly less aggressive in terms of both progression-free and total survival. We identified a small cohort of WHO grade II-III astrocytomas that harbored the IDH1 R132H mutation, as confirmed by both immunohistochemistry and molecular sequence analysis, which nonetheless had unexpectedly rapid recurrence and subsequent progression to glioblastoma. Among these four cases, the mean time to recurrence as glioblastoma was only 16 months and the mean total survival among the three patients who have died during the follow-up was only 31 months. We hypothesized that these tumors had other, unfavorable genetic or epigenetic alterations that negated the favorable effect of the IDH mutation. We applied genome-wide profiling with a methylation array (Illumina Infinium Human Methylation 450k) to screen for genetic and epigenetic alterations in these tumors. As expected, the methylation profiles of all four tumors were found to match most closely with IDH-mutant astrocytomas. Compared with a control group of four indolent, age-similar WHO grade II-III astrocytomas, the tumors showed markedly increased levels of overall copy number changes, but no consistent specific genetic alterations were seen across all of the tumors. While most IDH-mutant WHO grade II-III astrocytomas are relatively indolent, a subset may rapidly recur and progress to glioblastoma. The precise underlying cause of the increased aggressiveness in these gliomas remains unknown, although it may be associated with increased genomic instability.

  3. Expression of CD133 as a putative prognostic biomarker to predict intracranial dissemination of primary spinal cord astrocytoma.

    Science.gov (United States)

    Inoue, Tomoo; Endo, Toshiki; Nakamura, Taigen; Shibahara, Ichiyo; Endo, Hidenori; Tominaga, Teiji

    2017-11-24

    Spinal cord astrocytoma with intracranial dissemination carries a poor prognosis. The mechanisms leading to dissemination remain to be elucidated. A stem cell marker, CD133, was reported to predict recurrence patterns in intracranial glioblastoma. We evaluated the significance of CD133 as a putative prognostic biomarker to predict intracranial dissemination in spinal cord astrocytoma. This study included 14 consecutive patients with primary spinal cord astrocytoma treated from 1998 to 2014. Six of the patients were women and the patients' ages ranged from 12 to 75 years. Seven and 6 patients underwent open biopsy and partial resection of the tumors, respectively. After confirmation of the histological diagnoses, all patients were treated either with postoperative radiotherapy, chemotherapy, or a combination of both. To identify factors predictive of intracranial dissemination, we ranalyzed their clinical data including Ki-67 labeling index (LI), and CD133 expression. Intracranial dissemination was observed in 6 out of 14 patients. All 6 patients died during the follow-up period. Among the 8 patients without intracranial dissemination, 5 survived (p = 0.02). Median survival for the patients with intracranial dissemination was 22.7 months. CD133 expression was significantly higher in patients with intracranial dissemination (p = 0.04), while other variables did not indicate the dissemination. The expression of CD133 can be an efficient biomarker to predict intracranial dissemination in spinal cord astrocytoma. Recognition of high CD133 expression in surgical specimens and early detection of intracranial dissemination is important for the clinical management of spinal cord astrocytoma. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Laser interstitial thermal therapy for subependymal giant cell astrocytoma: technical case report.

    Science.gov (United States)

    Dadey, David Y A; Kamath, Ashwin A; Leuthardt, Eric C; Smyth, Matthew D

    2016-10-01

    Subependymal giant cell astrocytoma (SEGA) is a rare tumor occurring almost exclusively in patients with tuberous sclerosis complex. Although open resection remains the standard therapy, complication rates remain high. To minimize morbidity, less invasive approaches, such as endoscope-assisted resection, radiosurgery, and chemotherapy with mTOR pathway inhibitors, are also used to treat these lesions. Laser interstitial thermal therapy (LITT) is a relatively new modality that is increasingly used to treat a variety of intracranial lesions. In this report, the authors describe two pediatric cases of SEGA that were treated with LITT. In both patients the lesion responded well to this treatment modality, with tumor shrinkage observed on follow-up MRI. These cases highlight the potential of LITT to serve as a viable minimally invasive therapeutic approach to the management of SEGAs in the pediatric population.

  5. A new NFIA:RAF1 fusion activating the MAPK pathway in pilocytic astrocytoma

    DEFF Research Database (Denmark)

    Yde, Christina Westmose; Sehested, Astrid; Regué, Àngels Mateu

    2016-01-01

    are more rarely found. However, in some cases, no apparent cancer driver events can be identified. Here, we describe a novel fusion between the transcription factor nuclear factor 1A (NFIA) and Raf-1 proto-oncogene (RAF1) in a 5-year old boy with PA. The novel fusion was identified as part......Pilocytic astrocytoma (PA) is one of the most common brain cancers among children and activation of the Mitogen-Activated Protein Kinase (MAPK) pathway is considered the hallmark. In the majority of cases, oncogenic BRAF fusions or BRAF V600E mutations are observed, while RAF1 or NF1 alterations...... of a comprehensive genomic tumor profiling. We show that the NFIA:RAF1 fusion results in constitutive Raf1 kinase activity, leading to activation of downstream MEK1/2 cascade and increased proliferation of cancer cells. The NFIA:RAF1 fusion displayed distinct subcellular localization towards the plasma membrane...

  6. [Problems with flute playing: an otological problem? Case report of a peculiar cerebellar astrocytoma].

    Science.gov (United States)

    Forton, G; Verlooy, J; Cras, P; Parizel, P; Van de Heyning, P

    1992-01-01

    A rare case of cerebellar astrocytoma presenting as a cerebellopontine angle tumour is discussed. A 35-year old woman noticed a bizarre twitching and fatigability of the left upper lip while playing the flute. There was also a mild hearing loss on the left side and she sometimes felt unsure of herself when walking. A thorough examination by means of speech audiometry, electronystagmography, ABR, CT-scan and MRI revealed a large, partly calcified mass occupying the cerebellopontine angle. Only the histological examination of the surgical specimen revealed the true nature of the tumour. The special characteristics of this tumour and the unusual clinical course are discussed. The importance of a good histological diagnosis is stressed.

  7. High accuracy of arterial spin labeling perfusion imaging in differentiation of pilomyxoid from pilocytic astrocytoma

    Energy Technology Data Exchange (ETDEWEB)

    Nabavizadeh, S.A.; Assadsangabi, R.; Hajmomenian, M.; Vossough, A. [Perelman School of Medicine of the University of Pennsylvania, Department of Radiology, Children' s Hospital of Philadelphia, Philadelphia, PA (United States); Santi, M. [Perelman School of Medicine of the University of Pennsylvania, Department of Pathology, Children' s Hospital of Philadelphia, Philadelphia, PA (United States)

    2015-05-01

    Pilomyxoid astrocytoma (PMA) is a relatively new tumor entity which has been added to the 2007 WHO Classification of tumors of the central nervous system. The goal of this study is to utilize arterial spin labeling (ASL) perfusion imaging to differentiate PMA from pilocytic astrocytoma (PA). Pulsed ASL and conventional MRI sequences of patients with PMA and PA in the past 5 years were retrospectively evaluated. Patients with history of radiation or treatment with anti-angiogenic drugs were excluded. A total of 24 patients (9 PMA, 15 PA) were included. There were statistically significant differences between PMA and PA in mean tumor/gray matter (GM) cerebral blood flow (CBF) ratios (1.3 vs 0.4, p < 0.001) and maximum tumor/GM CBF ratio (2.3 vs 1, p < 0.001). Area under the receiver operating characteristic (ROC) curves for differentiation of PMA from PA was 0.91 using mean tumor CBF, 0.95 using mean tumor/GM CBF ratios, and 0.89 using maximum tumor/GM CBF. Using a threshold value of 0.91, the mean tumor/GM CBF ratio was able to diagnose PMA with 77 % sensitivity, 100 % specificity, and a threshold value of 0.7, provided 88 % sensitivity and 86 % specificity. There was no statistically significant difference between the two tumors in enhancement pattern (p = 0.33), internal architecture (p = 0.15), or apparent diffusion coefficient (ADC) values (p = 0.07). ASL imaging has high accuracy in differentiating PMA from PA. The result of this study may have important applications in prognostication and treatment planning especially in patients with less accessible tumors such as hypothalamic-chiasmatic gliomas. (orig.)

  8. Subependymal giant cell astrocytoma: one case report and review of literature

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    Juan WANG

    2014-12-01

    Full Text Available Background Subependymal giant cell astrocytoma (SEGA is a rare kind of central nervous system tumor typically occurring in children or adolescents under the age of 20. The tumor commonly arises in the region of the foramen of Monro. Most SEGA patients present distinctive histopathological and immunohistochemical characteristics.  Methods The clinical features, histopathological findings and immunohistochemical staining in one case of SEGA were analyzed, and the diagnosis and differential diagnosis of this disease with literature review were studied.  Results A 13-year-old female patient presented dizziness, headache and vomiting. Cranial MRI examination showed abnormal signals in the left lateral ventricle near the foramen of Monro, and exhibited heterogeneous enhancement after contrast. Histologically, the tumor was composed of clustering of fibrillated spindle cells and giant cells with abundant cytoplasm, and they were mixed. Glassy hyaline cytoplasm and eccentric vesicular nuclei with prominent nucleoli were frequently seen in the giant tumor cells. Some of the giant cells appeared to resemble gemistocytic astrocytes or ganglion cells. Considerable nuclear pleomorphism and multinuclear cells were frequently seen. There was no significant microvascular proliferation or necrosis. Immunohistochemical findings showed diffuse and strong positivity in tumor cells for vimentin (Vim, and partial positivity for S-100 protein (S-100, epithelial membrane antigen (EMA and glial fibrillary acidic protein (GFAP. A few giant tumor cells were positive for synaptophysin (Syn, but negative for neurofilament protein (NF, neuronal nuclei (NeuN and cytokeratin (CK. Ki-67 labeling index was very low (< 1%.  Conclusions SEGA is a benign central nervous system tumor (WHOⅠ. It has distinctive clinical and histopathological features, and should be differentiated from gemistocytic astrocytoma, ependymoma, gangliocytoma and giant cell glioblastoma. doi: 10

  9. The effect of IDH1 mutation on the structural connectome in malignant astrocytoma.

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    Kesler, Shelli R; Noll, Kyle; Cahill, Daniel P; Rao, Ganesh; Wefel, Jeffrey S

    2017-02-01

    Mutation of the IDH1 gene is associated with differences in malignant astrocytoma growth characteristics that impact phenotypic severity, including cognitive impairment. We previously demonstrated greater cognitive impairment in patients with IDH1 wild type tumor compared to those with IDH1 mutant, and therefore we hypothesized that brain network organization would be lower in patients with wild type tumors. Volumetric, T1-weighted MRI scans were obtained retrospectively from 35 patients with IDH1 mutant and 32 patients with wild type malignant astrocytoma (mean age = 45 ± 14 years) and used to extract individual level, gray matter connectomes. Graph theoretical analysis was then applied to measure efficiency and other connectome properties for each patient. Cognitive performance was categorized as impaired or not and random forest classification was used to explore factors associated with cognitive impairment. Patients with wild type tumor demonstrated significantly lower network efficiency in several medial frontal, posterior parietal and subcortical regions (p < 0.05, corrected for multiple comparisons). Patients with wild type tumor also demonstrated significantly higher incidence of cognitive impairment (p = 0.03). Random forest analysis indicated that network efficiency was inversely, though nonlinearly associated with cognitive impairment in both groups (p < 0.0001). Cognitive reserve appeared to mediate this relationship in patients with mutant tumor suggesting greater neuroplasticity and/or benefit from neuroprotective factors. Tumor volume was the greatest contributor to cognitive impairment in patients with wild type tumor, supporting our hypothesis that greater lesion momentum between grades may cause more disconnection of core neurocircuitry and consequently lower efficiency of information processing.

  10. Epithelial Cell Transforming 2 and Aurora Kinase B Modulate Formation of Stress Granule-Containing Transcripts from Diverse Cellular Pathways in Astrocytoma Cells.

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    Weeks, Adrienne; Agnihotri, Sameer; Lymer, Jennifer; Chalil, Alan; Diaz, Roberto; Isik, Semra; Smith, Christian; Rutka, James T

    2016-06-01

    Stress granules are small RNA-protein granules that modify the translational landscape during cellular stress to promote survival. The RhoGTPase RhoA is implicated in the formation of RNA stress granules. Our data demonstrate that the cytokinetic proteins epithelial cell transforming 2 and Aurora kinase B (AurkB) are localized to stress granules in human astrocytoma cells. AurkB and its downstream target histone-3 are phosphorylated during arsenite-induced stress. Chemical (AZD1152-HQPA) and siRNA inhibition of AurkB results in fewer and smaller stress granules when analyzed using high-throughput fluorescent-based cellomics assays. RNA immunoprecipitation with the known stress granule aggregates TIAR and G3BP1 was performed on astrocytoma cells, and subsequent analysis revealed that astrocytoma stress granules harbor unique mRNAs for various cellular pathways, including cellular migration, metabolism, translation, and transcriptional regulation. Human astrocytoma cell stress granules contain mRNAs that are known to be involved in glioma signaling and the mammalian target of rapamycin pathway. These data provide evidence that RNA stress granules are a novel form of epigenetic regulation in astrocytoma cells, which may be targetable by chemical inhibitors and enhance astrocytoma susceptibility to conventional therapy, such as radiation and chemotherapy. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  11. Deciphering the finger prints of brain cancer astrocytoma in comparison to astrocytes by using near infrared Raman spectroscopy.

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    Banerjee, Hirendra Nath; Zhang, L

    2007-01-01

    To explore the biochemical differences between brain cancer cells Astrocytoma and normal cells Astrocyte, we investigated the Raman spectra of single cell from these two cell types and analyzed the difference in spectra and intensity. Raman spectrum shows the banding pattern of different compounds as detected by the laser. Raman intensity measures the intensity of these individual bands. The Raman spectra of brain cancer cells was similar to those of normal cells, but the Raman intensity of cancer cells was much higher than that of normal cells. The Raman spectra of brain cancer Astrocytoma shows that the structural changes of cancer cells happen so that many biological functions of these cells are lost. The results indicate that Raman spectra can offer the experimental basis for the cancer diagnosis and treatment.

  12. Pilocytic Astrocytoma of Fornix Mimicking a Colloid Cyst: Report of 2 Cases and Review of the Literature.

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    Sharifi, Guive; Rahmanzadeh, Reza; Lotfinia, Mahmoud; Rahmanzade, Ramin

    2018-01-01

    Colloid cyst is a gelatin-containing cyst in the brain almost always found in the third ventricle. The specific shape and location of these cysts, a round well-delineated mass in the rostral part of the third ventricle adjacent to the foramen of Monro, on imaging are the main findings for diagnosis. Several masses of the third ventricle masquerading colloid cysts on images have been reported. Based on different surgical approaches, preoperative misdiagnosis of colloid cyst may have great impact on prognosis. We report 2 cases that presented with severe headache and hydrocephalus, and their preoperative images were highly indicative of colloid cyst. Histopathologic investigations after tumor resection showed pilocytic astrocytoma of fornix in both cases. Fifteen cases of colloid cyst misdiagnosis with other masses have been reported thus far; among them, 2 cases were pilocytic astrocytoma. In this study we report 2 other cases. Furthermore, we discuss additional clues helping to differentiate pilocytic astrocytoma from colloid cyst on images. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Surgical Management of Pilocytic Astrocytoma of the Optic Nerve: A Case Report and Review of the Literature

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    Ifeoluwa Apanisile

    2017-01-01

    Full Text Available Optic nerve astrocytomas (ONAs are frequent types of optic nerve gliomas (ONGs, which can affect the visual pathway. An 18-year-old male patient was admitted to our department with right-sided intraorbital/retrobulbar swelling, which progressively grew over several months. Clinical examination showed right-sided diplopia, mydriasis, low visual acuity (0.4, exophthalmus (3 cm, epiphora, and severe retrobulbar pain. There was a family history of high-grade (IV astrocytomas in which two of the family members died due to the disease. Preoperative MRI scan revealed a soft tissue mass around the retrobulbar area of the right eye with intact orbital bony walls. Surgery was performed whereby it was dissected freely from the muscles and was separated from the optic nerve and the globe. Histopathologic analysis confirmed a benign astrocytoma. The follow-up examination revealed no recurrent or residual tumor. A systemic review of the literature indicates that early diagnosis and experienced multidisciplinary management are required in case of unilateral, resectable forms of ONAs with no distant metastasis, in order to provide a long-time survival of patients. Surgical intervention of unilateral ONAs is a relatively safe procedure, allowing complete or partial tumor removal with minimal morbidity and low recurrence rate.

  14. Malignant Trigeminal Nerve Sheath Tumor and Anaplastic Astrocytoma Collision Tumor with High Proliferative Activity and Tumor Suppressor P53 Expression

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    Maher Kurdi

    2014-01-01

    Full Text Available Background. The synchronous development of two primary brain tumors of distinct cell of origin in close proximity or in contact with each other is extremely rare. We present the first case of collision tumor with two histological distinct tumors. Case Presentation. A 54-year-old woman presented with progressive atypical left facial pain and numbness for 8 months. MRI of the brain showed left middle cranial fossa heterogeneous mass extending into the infratemporal fossa. At surgery, a distinct but intermingled intra- and extradural tumor was demonstrated which was completely removed through left orbitozygomatic-temporal craniotomy. Histopathological examination showed that the tumor had two distinct components: malignant nerve sheath tumor of the trigeminal nerve and temporal lobe anaplastic astrocytoma. Proliferative activity and expressed tumor protein 53 (TP53 gene mutations were demonstrated in both tumors. Conclusions. We describe the first case of malignant trigeminal nerve sheath tumor (MTNST and anaplastic astrocytoma in collision and discuss the possible hypothesis of this rare occurrence. We propose that MTNST, with TP53 mutation, have participated in the formation of anaplastic astrocytoma, or vice versa.

  15. Everolimus in the treatment of subependymal giant cell astrocytomas, angiomyolipomas, and pulmonary and skin lesions associated with tuberous sclerosis complex

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    Franz DN

    2013-10-01

    Full Text Available David Neal Franz Department of Pediatrics, Tuberous Sclerosis Clinic, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA Abstract: Tuberous sclerosis complex (TSC is an autosomal dominant genetic disorder caused by inactivating mutations in either the TSC1 or TSC2 genes. It is characterized by the development of multiple, benign tumors in several organs throughout the body. Lesions occur in the brain, kidneys, heart, liver, lungs, and skin and result in seizures and epilepsy, mental retardation, autism, and renal and pulmonary organ system dysfunction, as well as other complications. Elucidation of the molecular pathways and etiological factors responsible for causing TSC has led to a paradigm shift in the management and treatment of the disease. TSC1 or TSC2 mutations lead to constitutive upregulation of the mammalian target of rapamycin pathway, which affects many cellular processes involved in tumor growth. By targeting mammalian target of rapamycin with everolimus, an orally active rapamycin derivative, clinically meaningful and statistically significant reductions in tumor burden have been achieved for the main brain (subependymal giant cell astrocytoma and renal manifestations (angiomyolipoma associated with TSC. This review provides an overview of TSC, everolimus, and the clinical trials that led to its approval for the treatment of TSC-associated subependymal giant cell astrocytoma and renal angiomyolipoma. Keywords: everolimus, subependymal giant cell astrocytoma, angiomyolipomas, lymphangioleiomyomatosis, facial angiofibromas, tuberous sclerosis complex

  16. Pilocytic astrocytoma with angiocentric arrangement: a case report and literature review

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    WANG Yin

    2013-04-01

    Full Text Available Background Pilocytic astrocytoma (PA is a low-grade glioma that occurs mainly in the cerebellum of children and young adults. This article is to report a rare case of PA with angiocentricarrangement in the supratentorial region of a 28-year-old male. The pathomorphism of this tumor isdifferent from that of typical PA, since most tumor cells grow in single layer around the hyalinized degenerative vessels, that is to say, angiocentric pattern. This paper aims to discuss the clinical, imaging and pathological features of PA with angiocentric arrangement and clinicopathological differentiations from relevant tumors, so as to improve the ability of diagnosing and differentiating this kind of tumor. Methods and Results A 28-year-old male with no significant past history presented with repeated grand mal seizures and did not recover in the treatment with antiepileptic drugs. Physical and neurological examinations were normal. Electroencephalography (EEG found no typical epileptic wave or focal δ wave. CT and MRI showed a superficial cystic mass with a mural nodule and clear boundary in the left frontal cortex. During the resection of the tumor, the lesion was identified as cystic structure on the surface and solid structure within the cyst wall. Optical microscopy findings revealed that tumour cells with round or oval nuclei and cytoplasm showing slender hair-like protuberance of both ends were arranged in single layer around hyalinized blood vessels. Some tumor cells with fusiform nuclei showed compact fascicles or loose stellate reticulum. Rosenthal fibers and eosinophilic granular bodies were occasionally seen. According to immunohistochemical staining, the tumor cells were diffusely positive for glial fibrillary acidic protein (GFAP, Vimentin (Vim, S-100 protein (S-100, Nestin, CD56, and focally positive for Olig2, while the tumor cells were negative for epithelial membrane antigen (EMA, isocitrate dehydrogenase 1 (IDH1, P53, neuronal nuclei

  17. Supratentorial tumors typical of the infantile age: desmoplastic infantile ganglioglioma (DIG) and astrocytoma (DIA). A review.

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    Bianchi, F; Tamburrini, G; Massimi, L; Caldarelli, M

    2016-10-01

    Desmoplastic infantile gangliogliomas (DIGs) and desmoplastic infantile astrocytomas (DIAs) are tumors typical of the infantile age. A large size, with a mixed solid and cystic component, clinical presentation with progressing signs of increased intracranial pressure, a prominent benign desmoplastic structure at histological examination, and a favorable clinical course in the majority of cases are the prominent features of these tumors. The objective of the present paper was to review the pertinent literature on the topic together with our personal experience, with the aim of an updated review of the subject. Only 28 papers are present in the literature devoted to DIGs and DIAs, most of them reporting on single cases or small series, with a total of 107 patients aged from 5 days to 48 months with a slight male prevalence. Most of the reported cases refer to supratentorial and hemispheric locations, a few cases involving the hypothalamic region, the posterior fossa, and the spinal cord. The typical MRI appearance is of large mixed solid and cystic tumors with a spontaneous hyperintense T2 appearance of the solid part which also shows a strong contrast enhancement. Mixed ganglionic and astrocytic cells are identifiable in DIGs, whereas DIAs are typically featured by the exclusive presence of glial cells. In both cases, more primitive cells may be observed, which present a higher number of mitoses and these areas can mimic the features of malignant astrocytomas. Surgery represents the treatment of choice; however, radical removal has been reported as possible only in around 30 % of the cases: the low age of the patients together with their low weight and the large size of and the hyper-vascularized structure of the tumors represent the main factors limiting surgery. Pure observation is considered as first choice in children undergoing a partial/subtotal tumor resection, chemotherapic regimens being considered in cases of recurrences after a second look surgery

  18. Prognostic value of coexistence of abnormal expression of micro-RNA-200b and cyclic adenosine monophosphate-responsive element-binding protein 1 in human astrocytoma.

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    Zhang, Jun-qing; Yao, Qing-he; Kuang, Yong-qin; Ma, Yuan; Yang, Li-bin; Huang, Hai-dong; Cheng, Jing-ming; Yang, Tao; Liu, En-yu; Liang, Liang; Fan, Ke-xia; Zhao, Kai; Xia, Xun; Gu, Jian-wen

    2014-10-01

    Our aim was to investigate the expression of micro-RNA-200b (miR-200b) and cAMP-responsive element-binding protein 1 (CREB-1) in astrocytoma and its efficacy for predicting outcome. Both miR-200b and CREB-1 messenger RNA expression was measured in 122 astrocytomas and 30 nonneoplastic brain specimens by quantitative real-time polymerase chain reaction. Expression of miR-200b was significantly lower in astrocytoma than in nonneoplastic brain (P RNA expression was significantly elevated in the tumors (P < .001). Both miR-200b down-regulation and CREB-1 up-regulation were significantly associated with advanced pathologic grade (P = .002 and P = .006, respectively). Low miR-200b expression correlated negatively with Karnofsky performance score (P = .03), and high CREB-1 expression correlated positively with mean tumor diameter (P = .03). By Kaplan-Meier analysis, low miR-200b, high CREB-1, and coexistence of abnormal miR-200b and CREB-1 expression (low miR-200b/high CREB-1) were predictive of shorter progression-free survival and overall survival in both grade III and grade IV astrocytoma. By multivariate analysis, only low miR-200b/high CREB-1 expression was an independent prognostic factor for poor prognosis in astrocytoma of advanced grade. Both miR-200b and CREB-1 may play important cooperative roles in the progression of human astrocytoma. The efficacy of miR-200b and CREB-1 together as a predictor of prognosis in astrocytoma patients is shown for the first time. Copyright © 2014. Published by Elsevier Inc.

  19. Pediatric high-grade astrocytomas: a distinct neuro-oncological paradigm.

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    Gerges, Noha; Fontebasso, Adam M; Albrecht, Steffen; Faury, Damien; Jabado, Nada

    2013-01-01

    Brain tumors are the leading cause of cancer-related death in children. High-grade astrocytomas (HGAs), in particular, are lethal in children across all ages. Integrative genome-wide analyses of the tumor's genome, transcriptome and epigenome, using next-generation sequencing technologies and genome-wide DNA methylation arrays, have provided valuable breakthroughs in our understanding of the pathogenesis of HGAs across all ages. Recent profiling studies have provided insight into the epigenetic nature of gliomas in young adults and HGAs in children, particularly with the identification of recurrent gain-of-function driver mutations in the isocitrate dehydrogenase 1 and 2 genes (IDH1/2) and the epigenetic influence of their oncometabolite 2-hydroxyglutarate, as well as mutations in the histone 3 variant 3 gene (H3F3A) and loss-of-function mutations in the histone 3 lysine 36 trimethyltransferase gene (SETD2). Mutations in H3F3A result in amino acid substitutions at residues thought to directly (K27M) or indirectly (G34R/V) affect histone post-translational modifications, suggesting they have the capacity to affect the epigenome in a profound manner. Here, we review recent genomic studies, and discuss evidence supporting the molecular characterization of pediatric HGAs to complement traditional approaches, such as histology of resected tumors. We also describe newly identified molecular mechanisms and discuss putative therapeutic approaches for HGAs specific to pediatrics, highlighting the necessity for the evolution of HGA disease management approaches.

  20. Low-grade astrocytoma: surgical outcomes in eloquent versus non-eloquent brain areas

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    André de Macedo Bianco

    2013-01-01

    Full Text Available A retrospective study of 81 patients with low-grade astrocytoma (LGA comparing the efficacy of aggressive versus less aggressive surgery in eloquent and non-eloquent brain areas was conducted. Extent of surgical resection was analyzed to assess overall survival (OS and progression- free survival (PFS. Degree of tumor resection was classified as gross total resection (GTR, subtotal resection (STR or biopsy. GTR, STR and biopsy in patients with tumors in non-eloquent areas were performed in 31, 48 and 21% subjects, whereas in patients with tumors in eloquent areas resections were 22.5, 35 and 42.5%. Overall survival was 4.7 and 1.9 years in patients with tumors in non-eloquent brain areas submitted to GTR/STR and biopsy (p=0.013, whereas overall survival among patients with tumors in eloquent area was 4.5 and 2.1 years (p=0.33. Improved outcome for adult patients with LGA is predicted by more aggressive surgery in both eloquent and non-eloquent brain areas.

  1. Cranial Pilocytic Astrocytoma With Spinal Drop Metastasis in an Adult: Case Report and Literature Review.

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    Munshey, Aasheen; Moore, Justin; Maclean, Catriona; Longano, Anthony; Goldschlager, Tony

    2017-02-01

    Pilocytic astrocytoma (PA) is a benign neoplasm that typically occurs in the brain within the pediatric and adolescent age groups and is uncommon in adults. It rarely occurs within the ventricles, and the overall prognosis is favorable. A PA of the brain with spinal metastasis at presentation has never been reported in an adult. We report a case of a 47-year-old man presenting with sudden-onset frontal headache associated with nausea and lethargy in addition to a background of a longer history of back pain and headache. Radiologic imaging revealed an acute intraparenchymal hemorrhage in the right parieto-occipital lobes with intraventricular extension within a peripherally enhancing heterogeneous lesion. Magnetic resonance imaging of the spine revealed a sacral intradural tumor. The patient underwent surgical resection of the intracranial mass followed by debulking of the spinal lesion. Histopathologic study revealed that both the cranial and spinal tumors were PA. This case illustrates a unique instance of hemorrhage into a cerebral PA with a spinal metastasis. To our knowledge, this is the first such case reported in an adult. We review the literature on the subject. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Subependymal Giant Cell Astrocytoma Presenting with Tumoral Bleeding: A Case Report

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    Kim, Jae-Young; Lee, Kyung-Hwa; Kim, Seul-Kee

    2017-01-01

    We report a rare case of subependymal giant cell astrocytoma (SEGA) associated with tumoral bleeding in a pediatric patient without tuberous sclerosis complex (TSC). A 10-year-old girl presented with a 2-week history of an increasingly aggravating headache. Brain magnetic resonance imaging revealed an approximately 3.6-cm, well-defined, heterogeneously enhancing mass with multistage hemorrhages on the right-sided foramen of Monro. The tumor was completely resected using a transcallosal approach. Intraoperatively, the mass presented as a gray-colored firm tumor associated with acute and subacute hemorrhages. The origin of the mass was identified as the ventricular septum adjacent to the foramen of Monro. A pathological analysis revealed pleomorphic multinucleated eosinophilic tumor cells with abundant cytoplasm. These cells showed positive staining for the glial fibrillary acidic protein and S100 protein. A diagnosis of SEGA was established. The patient recovered without any neurological symptoms. There was no evidence of TSC. The radiological follow-up showed no recurrence for 2 years. This was a case of SEGA with intratumoral hemorrhage, for which a favorable outcome was achieved, without any neurological deficit after tumoral resection. PMID:28516078

  3. A new NFIA:RAF1 fusion activating the MAPK pathway in pilocytic astrocytoma.

    Science.gov (United States)

    Yde, Christina Westmose; Sehested, Astrid; Mateu-Regué, Àngels; Østrup, Olga; Scheie, David; Nysom, Karsten; Nielsen, Finn Cilius; Rossing, Maria

    2016-10-01

    Pilocytic astrocytoma (PA) is one of the most common brain cancers among children and activation of the Mitogen-Activated Protein Kinase (MAPK) pathway is considered the hallmark. In the majority of cases, oncogenic BRAF fusions or BRAF V600E mutations are observed, while RAF1 or NF1 alterations are more rarely found. However, in some cases, no apparent cancer driver events can be identified. Here, we describe a novel fusion between the transcription factor nuclear factor 1A (NFIA) and Raf-1 proto-oncogene (RAF1) in a 5-year old boy with PA. The novel fusion was identified as part of a comprehensive genomic tumor profiling. We show that the NFIA:RAF1 fusion results in constitutive Raf1 kinase activity, leading to activation of downstream MEK1/2 cascade and increased proliferation of cancer cells. The NFIA:RAF1 fusion displayed distinct subcellular localization towards the plasma membrane indicative of Raf-1 activation, in contrast to both wild type NFIA and Raf-1, which were localized in the nucleus and cytoplasm, respectively. In conclusion, our data support the existence of rare oncogenic RAF1 fusions with constitutive Raf-1 activity. This highlights the need for broad genetic testing in order to refine diagnostics of PA and to unravel potential treatment options, e.g. with MEK inhibitors. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  4. Desmoplastic astrocytoma: new insights into its clinical profile, diagnosis, and treatment.

    Science.gov (United States)

    Rojas-Medina, L M; Carrasco-Moro, R; Rivero-Garvía, M; Esteban-Fernández, L; Rivas-Infante, E; Márquez-Rivas, J

    2016-09-01

    Desmoplastic astrocytoma (DA) is a rare intracranial tumor which usually affects pediatric patients. The aim of this study is to describe the clinical features and management of DA based on a joint analysis of the cases reported in the scientific literature. A thorough review was carried out, gathering those pathologically proven DAs reported since the first description of this entity. Two new own cases were included in order to illustrate this review. Epidemiological, clinical, radiological, therapeutic, and follow-up data were analyzed with the software SPSS version 20. A total of 52 DAs were recorded. Most cases occurred in the first 2 years of life, although older patients were also reported. Patients mainly presented symptoms and signs of elevated intracranial pressure. According to their radiological features, we were able to classify DAs in four main groups, with distinct differential diagnosis and prognosis. After treatment, 14.2 % of patients presented persistent neurological impairment and the mortality rate was close to 10 %. DAs can be diagnosed at any age from birth to adolescence. These neoplasms can show up a wider range of radiological morphologies than previously thought. Surgery represents the treatment of choice for DAs, although chemotherapy can also be useful in the setting of recurrence or progression of the disease. Those DAs lacking classic radiological features, especially type 4 tumors, were linked with a poorer clinical outcome.

  5. Flow cytometric analysis of cellular DNA content in human astrocytomas and oligodendrogliomas.

    Science.gov (United States)

    Ahyai, A

    1988-01-01

    This report presents a flow-cytometric analysis of cellular DNA in biopsies and primary cell cultures of 21 human astrocytomas and 19 oligodendrogliomas. A distinct correlation between histological dedifferentiation and pathological DNA distribution was found. Classification was made according to increasing histological anaplasia, corresponding to a four-grade scale and proliferation index (PI). Four types of gliomas were defined according to characteristic DNA patterns and proliferative activities in comparison to their histological grading: 1. purely diploid DNA patterns with low 4C (premitotic) peaks and PI values up to 10 in well-differentiated gliomas; 2. increase of tetraploid cells and PI of 10-16 in tumors with histological grades II or II-III; 3. diploid-tetraploid DNA distribution with PI values up to 30-31 and malignancy grade III; 4. polyploid and aneuploid karyograms with excessive 4C increase, emerging in grade III and especially grade III-IV of these gliomas. Varying DNA distribution during tumor development could be observed in a malignant transformation of an oligodendroglioma I to a glioblastoma after a course of 3 1/2 years. A more detailed subdivision of these tumors according to their DNA content and proliferative activity was achieved. With the exception of occasional variation in karyograms, DNA distribution usually remained stable in primary tissue cultures (PTC).

  6. Effectiveness of interferon-beta and temozolomide combination therapy against temozolomide-refractory recurrent anaplastic astrocytoma

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    Arai Hajime

    2007-08-01

    Full Text Available Abstract Background Malignant gliomas recur even after extensive surgery and chemo-radiotherapy. Although a relatively novel chemotherapeutic agent, temozolomide (TMZ, has demonstrated promising activity against recurrent glioma, the effects last only a few months and drug resistance develops thereafter in most cases. Induction of O6-methylguanine-DNA methyltransferase (MGMT in tumors is considered to be responsible for resistance to TMZ. Interferon-beta has been reported to suppress MGMT in an experimental glioma model. Here we report a patient with TMZ-refractory anaplastic astrocytoma (AA who was treated successfully with a combination of interferon-beta and TMZ. Case presentation A patient with recurrent AA after radiation-chemotherapy and stereotactic radiotherapy was treated with TMZ. After 6 cycles, the tumor became refractory to TMZ, and the patient was treated with interferon-beta at 3 × 106 international units/body, followed by 5 consecutive days of 200 mg/m2 TMZ in cycles of 28 days. After the second cycle the tumor decreased in size by 50% (PR. The tumor showed further shrinkage after 8 months and the patient's KPS improved from 70% to 100%. The immunohistochemical study of the initial tumor specimen confirmed positive MGMT protein expression. Conclusion It is considered that interferon-beta pre-administration increased the TMZ sensitivity of the glioma, which had been refractory to TMZ monotherapy.

  7. MULTIFOCAL GLIOBLASTOMA MULTIFORME PRECEDED BY A GEMISTOCYTIC ASTROCYTOMA AND DYSREGULATED IMMUNE RESPONSE.

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    Ilian Koev

    2014-06-01

    Full Text Available Glioblastoma multiforme (GBM is known to be the most common malignant form of astroglial brain tumors. The etiology, cellular and molecular pathogenic mechanisms remain unclear to a great extent. Recent research indicates the role of the immune system in malignant glioma and especially in triggering the mechanisms of local resistance and systemic immune suppression. There is accumulating evidence that the concept of the CNS as an immune-privileged organ is no longer valid. Recent advances demonstrate that it is an immunologically active site, with complex immune responses mostly based on innate immune processes. Multifocal gliomas with varying histopathological appearance are extremely rare. We report the only case of GBM preceded by a gemistocytic astrocytoma with a very short survival time of just 3 months after the onset of complaints. Interestingly, a normal CD4/CD8 ratio but prominent change in the regulatory T cell lineage was recorded. The elevation of the suppressor CD8+CD11b+ cells and the reduction of cytotoxic CD8+CD11b- cells indicate the prevalence of a suppressor phenotype which provides an explanation for the occurrence of the second malignant tumor, the rapid tumor progression and fatal outcome.

  8. Secondary Glioblastoma Multiforme in a Child with Disseminated Juvenile Pilocytic Astrocytoma

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    C. S. Amene

    2012-01-01

    Full Text Available Secondary glioblastoma multiforme (sGBM can occur after a long latency period following radiation treatment of various diseases including brain tumors, leukemia, and more benign disorders like tinea capitis. Outcomes of radiation-induced sGBM remain poor in both children and adults. We report a case of a 16-year-old girl with a history of disseminated juvenile pilocytic astrocytoma treated with chemotherapy and craniospinal radiation 9 years prior who developed sGBM in the absence of a tumor predisposition syndrome. She presented with a several-week history of headaches and no acute findings on computed tomography compared to baseline neuroimaging 3 months prior. Repeat computed tomography performed just 3 weeks later for worsening headaches revealed a new large posterior fossa tumor where pathology confirmed the diagnosis of sGBM. In spite of maximal surgical resection, reirradiation, and adjuvant chemotherapy, she died 1 year postdiagnosis. Our case highlights the potential late effects of high-dose cranial radiation, how symptomatology may precede neuroimaging findings, and the rapid formation of sGBM that mirrors that of de novo Glioblastoma Multiforme.

  9. Induction of cellular proliferation in a human astrocytoma cell line by a Trypanosoma cruzi-derived antigen: a mechanism of pathogenesis?

    Science.gov (United States)

    Duran-Rehbein, G A; Vargas-Zambrano, J C; Cuéllar, A; Puerta, C J; Gonzalez, J M

    2017-01-30

    Trypanosoma cruzi can compromise the human central nervous system (CNS) during acute infection or reactivation in immune-suppressed hosts. Astrocytes have been identified as targets of T. cruzi's CNS infection in humans. Despite a high degree of parasitism and cellular lysis by T. cruzi in vitro the number of astrocytoma cells did not change when compared to uninfected cultures. This work evaluated cellular proliferation, changes in Major Histocompatibility Complex (MHC) expression as a reflection of antigen processing, and cytokine (IL-6 & IL-8) secretion in a human astrocytoma cell line exposed to a trypomastigote-derived antigen. Light microscopy was used to evaluate the number of cells; MHC molecule expression, cell cycle and cytokine secretion were assessed by flow cytometry. The number of astrocytoma cells increased proportional to the amount of antigen used and the percentage of cells in G2/M phase was higher when compared to control cultures. Antigen exposure increased expression of MHC class II, but not MHC class I in comparison to cultures incubated without antigen. Astrocytoma cell secretion of IL-6 and IL-8 was unaffected by antigen exposure. These results suggest the participation of a trypomastigote-derived mediator that induces astrocytoma cell proliferation without an inflammatory response; which may contribute to the pathogenesis of neurologic Chagas disease.

  10. EGR-1 is regulated by N-methyl-D-aspartate-receptor stimulation and associated with patient survival in human high grade astrocytomas.

    Science.gov (United States)

    Mittelbronn, Michel; Harter, Patrick; Warth, Arne; Lupescu, Adrian; Schilbach, Karin; Vollmann, Henning; Capper, David; Goeppert, Benjamin; Frei, Karl; Bertalanffy, Helmut; Weller, Michael; Meyermann, Richard; Lang, Florian; Simon, Perikles

    2009-04-01

    Early growth response-1 (EGR-1) is considered a central regulator in tumor cell proliferation, migration and angiogenesis and a promising candidate for gene therapy in human astrocytomas. However, conflicting data have been reported suggesting that both tumor promoting and anti-tumor activity of EGR-1 and its regulation, expression and prognostic significance still remain enigmatic. Our study explored EGR-1 expression and regulation in astrocytomas and its association with patient survival. As we detected two EGR-1 mRNA variants, one containing a N-methyl-D-aspartate-receptor (NMDA-R) responsive cytoplasmic polyadenylation element (CPE), further experiments were performed to determine the functional role of this pathway. After NMDA stimulation of SV-FHAS and neoplastic astrocytes, real-time polymerase chain reaction showed an increase of the CPE, containing EGR-1 splice variant only in astrocytoma cells. The surface expression and functionality of NMDA-R were demonstrated by flow cytometric analysis and measurement of increased intracellular Ca(2+). EGR-1 was mainly restricted to tumor cells expressing NMDA-R and significantly up-regulated in astrocytic tumors compared with normal brain. Further, EGR-1 expression was significantly (P < 0.007) associated with enhanced patient survival and was an independent prognostic factor in multivariate analysis in high grade astrocytomas. The NMDA-R-mediated EGR-1 expression, therefore, seems to be a promising target for novel clinical approaches to astrocytoma treatment.

  11. Hypothalamic-Optochiasmatic Pilocytic Astrocytoma Associated with Occipital and Sacral Spinal Cavernomas: A Mere Coincidence or a True Association?

    Science.gov (United States)

    Abou Al-Shaar, Hussam; Raheja, Amol; Palmer, Cheryl A; Schmidt, Meic H; Couldwell, William T

    2016-06-01

    The co-occurrence of cerebral gliomas and cavernous angiomas is rarely encountered in clinical practice. All reported cases with such association have occurred within the brain with none involving the spinal cord. The authors report the case of a hypothalamic-optochiasmatic pilocytic astrocytoma coexisting with right occipital and sacral spinal cavernomas. This 30-year-old man had an 8-year history of chronic lower back pain. Spinal magnetic resonance imaging (MRI) demonstrated an 8.2-cm expansile multilobulated heterogeneously enhancing intradural mass within the sacral spinal canal, extending into the bilateral S1 and left S2 foramina. Brain MRI depicted a 2.9-cm lobulated heterogeneously enhancing sellar-suprasellar solid and cystic mass expanding the sella and displacing the infundibulum to the right, with a normal-appearing pituitary gland inside the sella, and an extensive supratentorial and infratentorial superficial hemosiderosis. L5-S4 laminectomy and pterional craniotomy were performed for the resection of these lesions. Histopathologic examination revealed a sacral spinal cavernoma and a suprasellar hypothalamic-optochiasmatic pilocytic astrocytoma. The coexistence of hypothalamic-optochiasmatic pilocytic astrocytoma and occipital and sacral spinal cavernomas has not been reported previously. Especially for radiologically atypical suprasellar lesions, hypothalamic-optochiasmatic glioma should be included in the differential diagnosis of masses that can expand the sella. Besides previously postulated hypotheses of viral-induced or angiogenic factor-induced glial growth, we hypothesize that neoplastic origins of hypothalamic-optochiasmatic glioma might be due to the irritative mechanisms resulting from the frequent bleeds occurring from the spinal or cranial cavernoma. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. A dangerous liaison: Leptin and sPLA2-IIA join forces to induce proliferation and migration of astrocytoma cells.

    Science.gov (United States)

    Martín, Rubén; Cordova, Claudia; Gutiérrez, Beatriz; Hernández, Marita; Nieto, María L

    2017-01-01

    Glioblastoma, the most aggressive type of primary brain tumour, shows worse prognosis linked to diabetes or obesity persistence. These pathologies are chronic inflammatory conditions characterized by altered profiles of inflammatory mediators, including leptin and secreted phospholipase A2-IIA (sPLA2-IIA). Both proteins, in turn, display diverse pro-cancer properties in different cell types, including astrocytes. Herein, to understand the underlying relationship between obesity and brain tumors, we investigated the effect of leptin, alone or in combination with sPLA2-IIA on astrocytoma cell functions. sPLA2-IIA induced up-regulation of leptin receptors in 1321N1 human astrocytoma cells. Leptin, as well as sPLA2-IIA, increased growth and migration in these cells, through activation/phosphorylation of key proteins of survival cascades. Leptin, at concentrations with minimal or no activating effects on astrocytoma cells, enhanced growth and migration promoted by low doses of sPLA2-IIA. sPLA2-IIA alone induced a transient phosphorylation pattern in the Src/ERK/Akt/mTOR/p70S6K/rS6 pathway through EGFR transactivation, and co-addition of leptin resulted in a sustained phosphorylation of these signaling regulators. Mechanistically, EGFR transactivation and tyrosine- and serine/threonine-protein phosphatases revealed a key role in this leptin-sPLA2-IIA cross-talk. This cooperative partnership between both proteins was also found in primary astrocytes. These findings thus indicate that the adipokine leptin, by increasing the susceptibility of cells to inflammatory mediators, could contribute to worsen the prognosis of tumoral and neurodegenerative processes, being a potential mediator of some obesity-related medical complications.

  13. Axial MR diffusion tensor imaging and tractography in clinical diagnosed and pathology confirmed cervical spinal cord astrocytoma.

    Science.gov (United States)

    Zhao, Mangsuo; Shi, Bingxin; Chen, Tuoyu; Zhang, Yuqi; Geng, Tongchao; Qiao, Liyan; Zhang, Mingjie; He, Le; Zuo, Huancong; Wang, Guihuai

    2017-04-15

    To evaluate the diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) features of cervical spinal cord astrocytoma. Eleven patients with cervical spinal cord astrocytomas and 10 healthy volunteers were recruited in this study. Conventional magnetic resonance imaging (MRI) and axial DTI were performed on a 3.0T MRI system. Apparent diffusion coefficient (ADC), fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) values for the lesions were measured. DTT was performed using the principal diffusion direction method. ADC values of the lesions and the normal-appearing tissue around the tumour (NATAT) on T2-weighted imaging (T2WI) increased. The ADC values of the lesions were higher. The FA values of the lesions and the NATAT decreased significantly, with the lesions having lower FA values. The RD value (1.36±0.49) of the tumours was significantly higher than those found in the healthy controls, but similar for the AD value (1.84±0.56). There were no differences in ADC or FA values between lesions and NATAT in McCormick Type I vs. Type II patients. Based on the DTT, 7 patients with solid mass tumours were classified as Type I. One patient with a solid mass, 2 patients with cystic degeneration inside the lesions, and 1 patient with a cyst around the mass were classified as Type II. FA values of the cervical spinal cord astrocytoma decreased, but the ADC values increased. DTI was sensitive for the evaluation of pathological changes that could not be visualized on T2WI. Our preliminary study indicates that DTT can be used to guide operation planning, and that axial images of DTT may be more valuable. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Combined "Infiltrating Astrocytoma/Pleomorphic Xanthoastrocytoma" Harboring IDH1 R132H and BRAF V600E Mutations.

    Science.gov (United States)

    Yamada, Seiji; Kipp, Benjamin R; Voss, Jesse S; Giannini, Caterina; Raghunathan, Aditya

    2016-02-01

    Pleomorphic xanthoastrocytoma (PXA) has rarely been reported in combination with infiltrating glioma, historically interpreted as a "collision tumor." Isocitrate dehydrogenase 1 (IDH1) and BRAF V600E mutations are usually not concurrent. The former is typical of adult infiltrating gliomas, and the latter is identified in a variety of primary central nervous system neoplasms, including PXA, ganglioglioma, pilocytic astrocytoma, and rarely infiltrating gliomas. We report the case of a 56-year-old man presenting with seizures and headaches. Magnetic resonance imaging revealed a large right temporal lobe mass with low T1 and high T2/FLAIR signal and a discrete contrast-enhancing focus. Histologically, the tumor showed 2 distinct components: an infiltrating astrocytoma harboring 5 mitoses/10 high-power fields and a relatively circumscribed focus, resembling PXA with, at most, 2 mitoses/10 high-power fields. No microvascular proliferation or necrosis was present in either component. The infiltrating astrocytoma component contained numerous axons, whereas the PXA-like component had sparse axons, as demonstrated by the neurofilament immunostain. Both components were positive for the mutant IDH1 R132H and showed loss of ATRX expression, whereas BRAF V600E was restricted to the PXA-like component. On sequencing of the 2 components separately after microdissection, both showed identical IDH1 R132H and TP53 R273C point mutations, whereas the BRAF V600E mutation was limited to the PXA-like component. These findings are consistent with clonal expansion of a morphologically distinct focus, harboring a private BRAF V600E mutation within an IDH1-mutant glioma. Intratumoral heterogeneity and clonal evolution, as seems to have occurred here, suggest reevaluation of "collision tumors" as a concept.

  15. Inhibition of autophagy by 3-methyladenine protects 1321N1 astrocytoma cells against pyocyanin- and 1-hydroxyphenazine-induced toxicity.

    Science.gov (United States)

    McFarland, Amelia J; Anoopkumar-Dukie, Shailendra; Perkins, Anthony V; Davey, Andrew K; Grant, Gary D

    2012-02-01

    Central nervous system (CNS) infections due to Pseudomonas aeruginosa are difficult to treat and have a high mortality rate. Pyocyanin, a virulence factor produced by P. aeruginosa, has been shown to be responsible for the majority of P. aeruginosa's pathogenicity in mammalian cells. Several lines of evidence in respiratory cells suggest that this damage is primarily mediated by pyocyanin's ability to generate ROS and deplete host antioxidant defense mechanisms. However, it has yet to be established whether pyocyanin or 1-hydroxyphenazine have potential toxicity to the CNS. Therefore, the aim of this study was to compare the CNS toxicity of pyocyanin and 1-hydroxyphenazine in vitro and to provide insight into mechanisms that underlie this toxicity using 1321N1 astrocytoma cells. To achieve this, we investigated the contribution of oxidative stress and other mediators of cell death including autophagy, senescence and apoptosis. We show that oxidative stress is not a primary mediator of pyocyanin (0-100 μM) and 1-hydroxyphenazine (0-100 μM) induced toxicity in 1321N1 cells. Instead, our results suggest that autophagy may play a central role. The autophagy inhibitor 3-methyladenine (5 mM) protected 1321N1 astrocytoma cells against both pyocyanin and 1-hydroxyphenazine-induced cell injury and increased accumulation of acidic vesicular organelles, a hallmark of autophagy. Furthermore, apoptosis and senescence events may be secondary to autophagy in pyocyanin and 1-hydroxyphenazine-mediated cell injury. In conclusion, this study provides the first evidence on mechanisms underlying the toxicity of both pyocyanin and 1-hydroxyphenazine to astrocytoma cells and provides novel evidence suggesting that this toxicity may be mediated by the formation of acidic vesicular organelles, a hallmark of autophagic cell death.

  16. Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human astrocytoma cells.

    Science.gov (United States)

    Mori, Koichiro; Obara, Yutaro; Hirota, Mitsuru; Azumi, Yoshihito; Kinugasa, Satomi; Inatomi, Satoshi; Nakahata, Norimichi

    2008-09-01

    Neurotrophic factors are essential to maintain and organize neurons functionally; thereby neurotrophic factor-like substances or their inducers are expected to be applied to the treatment of neurodegenerative diseases such as Alzheimer's disease. In the present study, we firstly examined the effects of ethanol extracts of four edible mushrooms, Hericium erinaceus (Yamabushitake), Pleurotus eryngii (Eringi), Grifola frondosa (Maitake), and Agaricus blazei (Himematsutake), on nerve growth factor (NGF) gene expression in 1321N1 human astrocytoma cells. Among the four mushroom extracts, only H. erinaceus extract promoted NGF mRNA expression in a concentration-dependent manner. In addition, secretion of NGF protein from 1321N1 cells was enhanced by H. erinaceus extracts, and the conditioned medium of 1321N1 cells incubated with H. erinaceus extract enhanced the neurite outgrowth of PC12 cells. However, hericenones C, D and E, constituents of H. erinaceus, failed to promote NGF gene expression in 1321N1 cells. The enhancement of NGF gene expression by H. erinaceus extracts was inhibited by the c-jun N-terminal kinase (JNK) inhibitor SP600125. In addition, H. erinaceus extracts induced phosphorylation of JNK and its downstream substrate c-Jun, and increased c-fos expression, suggesting that H. erinaceus promotes NGF gene expression via JNK signaling. Furthermore we examined the efficacy of H. erinaceus in vivo. ddY mice given feed containing 5% H. erinaceus dry powder for 7 d showed an increase in the level of NGF mRNA expression in the hippocampus. In conclusion, H. erinaceus contains active compounds that stimulate NGF synthesis via activation of the JNK pathway; these compounds are not hericenones.

  17. BRAF V600E mutations are frequent in dysembryoplastic neuroepithelial tumors and subependymal giant cell astrocytomas.

    Science.gov (United States)

    Lee, Dakeun; Cho, Young Hye; Kang, So Young; Yoon, Nara; Sung, Chang Ohk; Suh, Yeon-Lim

    2015-03-01

    BRAF mutation has received a great deal of attention in neuro-oncology field, recently. This study aimed to investigate the incidence and the clinical significance of BRAF(V600E) in low-grade glial tumors. An institutional cohort of 105 brain tumors (51 dysembryoplastic neuroepithelial tumors (DNTs), 14 subependymal giant cell astrocytomas (SEGAs), 12 glioblastoma with neuronal marker expression (GBM-N), and 28 pleomorphic xanthoastrocytomas (PXAs)) from 100 patients were investigated for the presence of BRAF(V600E) by direct sequencing. We found frequent BRAF(V600E) in DNTs (26/51, 51%), SEGAs (6/14, 42.9%), and PXAs (14/28, 50%). In DNTs, BRAF(V600E) was more commonly detected in tumors with extra-temporal location (68.2% vs. 37.9%; P = 0.032). The diagnostic subgroups of tuberous sclerosis complex were not correlated with BRAF(V600E) in patients with SEGA (P = 0.533). One PXA case revealed a unique duplication mutation (p.Thr599dup) of codon 599. All GMB-N cases did not carry BRAF mutation. Our data indicate that BRAF(V600E) is a common genetic alteration in low-grade glial tumors with neuronal component or differentiation. High frequency of BRAF(V600E) in DNTs and SEGAs would be useful in the differential diagnosis, and also offers a potential specific treatment targeting BRAF(V600E) . © 2014 Wiley Periodicals, Inc.

  18. 4-Aminopyridine causes apoptosis and blocks an outward rectifier K+ channel in malignant astrocytoma cell lines.

    Science.gov (United States)

    Chin, L S; Park, C C; Zitnay, K M; Sinha, M; DiPatri, A J; Perillán, P; Simard, J M

    1997-04-15

    Among the ion channels and pumps activated by growth factor stimulation, K+ channels have been implicated in the growth and proliferation of several cancer cell lines. The role of these channels in central nervous system tumors, however, has not been described. This study used the malignant astrocytoma cell lines U87 and A172. 4-Aminopyridine (4-AP) inhibition of proliferation was dose dependent, and assessment using a TUNEL in situ assay revealed that apoptosis occurred in U87 cells with wild-type p53 but not in A172 cells with mutant p53 (24-hr incubation with mM 4-AP). In patch clamp experiments, we identified two types of K+ currents in both cell lines, a charybdotoxin-sensitive Ca2(+)-activated K+ channel and a 4-AP-sensitive outward rectifier K+ current. The outward rectifier current was blocked by 4-AP in a dose-dependent manner, with half-maximal block occurring at 3.9 mM. The blocking effect of 4 mM 4-AP was noticeable at potentials as low as -65 mV and was statistically significant at -60 mV and above, suggesting that 4-AP-sensitive current is active at physiological potentials. By contrast, charybdotoxin (1 microM) and tetraethylammonium. Cl (2 mM) blocked the Ca2(+)-activated K+ channel in both cell lines but had no appreciable effect on cell growth. Our findings reveal that 4-AP inhibits proliferation and the outward rectifier K+ channel in both U87 and A172 cells. More studies are needed, however, to describe the mechanism by which K+ channels influence proliferation and induce apoptosis.

  19. Desmoplastic infantile astrocytoma/ganglioglioma with rare BRAF V600D mutation.

    Science.gov (United States)

    Greer, Ashley; Foreman, Nicholas K; Donson, Andrew; Davies, Kurtis D; Kleinschmidt-DeMasters, B K

    2017-06-01

    Desmoplastic infantile astrocytoma (DIA) and desmoplastic infantile gangliogliomas (DIGs) are rare, massive, cystic and solid tumors of infants usually found in superficial cerebral hemispheres. They manifest prominent desmoplastic stroma, admixed neoplastic astrocytes, primitive-appearing small cells, and additional neoplastic ganglion cells in the case of DIGs. While v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutation is found in up to 50% of pediatric gangliogliomas, two recent studies found that it was rare in DIA/DIGs; we sought to assess BRAF status in DIA/DIGs from our institution. Departmental files from 2000 to 2016 were reviewed to identify cases. Clinical, neuroimaging, histological, and immunohistochemistry (IHC) features were assessed; the latter included IHC for astrocytic and neuronal markers and BRAF VE1. BRAF mutational assessment by Sanger and next-generation sequencing was attempted in all cases. All six identified cases (four males-two females; three DIA-three DIG) occurred in children <1-year old, were large, cerebral-hemispheric, cystic and solid, and enhancing tumors. Only one case, a DIG with prominent aggregates of neoplastic ganglion cells, showed either BRAF VE1 IHC positivity or mutation by Sanger and next-generation sequencing (rare c. 1799_1800delinsAT; p. V600D). Four of six archival cases were BRAF VE1 IHC negative, but failed mutational sequencing. Five of six classic DIA/DIGs were negative for BRAF mutation; previous series have identified BRAF mutation in two of 18 and one of 14 cases, although all were the more common BRAF V600E. We were unable to find other examples of glial tumors in public databases with this rare BRAF V600D mutation. Identification of BRAF mutational opens the possibility of BRAF-targeted therapies for the subset of DIA/DIG that clinically progress postresection. © 2016 Wiley Periodicals, Inc.

  20. Model-Based Evaluation of Spontaneous Tumor Regression in Pilocytic Astrocytoma.

    Directory of Open Access Journals (Sweden)

    Thomas Buder

    2015-12-01

    Full Text Available Pilocytic astrocytoma (PA is the most common brain tumor in children. This tumor is usually benign and has a good prognosis. Total resection is the treatment of choice and will cure the majority of patients. However, often only partial resection is possible due to the location of the tumor. In that case, spontaneous regression, regrowth, or progression to a more aggressive form have been observed. The dependency between the residual tumor size and spontaneous regression is not understood yet. Therefore, the prognosis is largely unpredictable and there is controversy regarding the management of patients for whom complete resection cannot be achieved. Strategies span from pure observation (wait and see to combinations of surgery, adjuvant chemotherapy, and radiotherapy. Here, we introduce a mathematical model to investigate the growth and progression behavior of PA. In particular, we propose a Markov chain model incorporating cell proliferation and death as well as mutations. Our model analysis shows that the tumor behavior after partial resection is essentially determined by a risk coefficient γ, which can be deduced from epidemiological data about PA. Our results quantitatively predict the regression probability of a partially resected benign PA given the residual tumor size and lead to the hypothesis that this dependency is linear, implying that removing any amount of tumor mass will improve prognosis. This finding stands in contrast to diffuse malignant glioma where an extent of resection threshold has been experimentally shown, below which no benefit for survival is expected. These results have important implications for future therapeutic studies in PA that should include residual tumor volume as a prognostic factor.

  1. TREATMENT OF PROGRESSION OF DIFFUSE ASTROCYTOMA BY HERBAL MEDICINE: CASE REPORT.

    Science.gov (United States)

    Trogrlić, Ivo; Trogrlić, Dragan; Trogrlić, Zoran

    2016-01-01

    The paper presents the results of the use of phytotherapy in a 33-year-old woman who, after finishing the oncological treatment of diffuse astrocytoma, had tumour progression. Phytotherapy was introduced after the tumour had progressed. It consisted of 4 types of herbal medicine which the subject was taking in form of tea once a day at regular intervals. The patient started phytotherapy along with temozolomide, which was the only oncological treatment she was under after the tumour had progressed. Following the finished chemotherapy, the patient continued the treatment with herbal medicine only. She regularly took phytotherapy without interruption and to the fullest extent for 30 months, and the results of treatment were monitored by periodic scanning using nuclear magnetic resonance technique. The control scanning that was conducted after the end of combined treatment with temozolomide and phytotherapy showed tumour regression. The patient continued with phytotherapy after finishing chemotherapy and, during the following 24 months, it was the sole treatment option. In that period, the regression of the tumour continued, until a control examination 30 months after the introduction of phytotherapy showed no clinical and radiological signs of tumour. The results presented in this research paper clearly indicate the potential of phytotherapy in the treatment of some types of brain tumours. A complete regression of tumour following the treatment with nothing but herbal medicine offers support for such claim. Future research should demonstrate the effectiveness of phytotherapy, as a supplementary form of brain tumour treatment, and the results of this research should be compared with the existing information on the effectiveness of the protocols currently used in the treatment of these types of tumour.

  2. Subependymal giant cell astrocytoma in a genetically negative tuberous sclerosis complex adult: Case report.

    Science.gov (United States)

    Konakondla, Sanjay; Jayarao, Mayur; Skrade, Jami; Giannini, Caterina; Workman, Michael J; Morgan, Chad J

    2016-11-01

    The well-described entity of Subependymal Giant Cell Astrocytoma (SEGA) in the setting of Tuberous Sclerosis Complex (TSC) is profound in current literature. It has been described in children as well as adults with or without identifiable clinical presentations of tuberous sclerosis. To our knowledge there has not been any report of a negative genetic workup of Tuberous Sclerosis Complex in an adult patient presenting with an isolated SEGA. We present a case of a 25-year-old female with no medical history who presented to the emergency room for headaches. Further workup included gadolinium enhanced MRI of the brain which revealed a homogenously enhancing mass in the left lateral ventricle with eccentric calcification and resultant obstructive hydrocephalus. A left frontal craniotomy with an interhemispheric transcallosal approach was taken for complete removal of the mass. Final pathological diagnosis was SEGA with suggestive cell population, positive GFAP and positive synaptophysin. Genetic testing included TSC1 (MLPA, DNA Sequencing) and TSC2 (MLPA, DNA Sequencing), which were all negative. The panel did not identify mutations associated with Tuberous Sclerosis. Rare cases of isolated SEGA have been reported in patients who do not have typical features of tuberous sclerosis, and may represent minimal penetrance of the disease with an attenuated phenotype. Negative genetic testing, as demonstrated, can be seen in adults with isolated SEGA. With a negative genetic workup of TSC, regular follow up may still be necessary; however this may prove to be low yield for identifying any TSC features in the future. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. A new GTF2I-BRAF fusion mediating MAPK pathway activation in pilocytic astrocytoma.

    Science.gov (United States)

    Tomić, Tajana Tešan; Olausson, Josefin; Wilzén, Annica; Sabel, Magnus; Truvé, Katarina; Sjögren, Helene; Dósa, Sándor; Tisell, Magnus; Lannering, Birgitta; Enlund, Fredrik; Martinsson, Tommy; Åman, Pierre; Abel, Frida

    2017-01-01

    Pilocytic astrocytoma (PA) is the most common pediatric brain tumor. A recurrent feature of PA is deregulation of the mitogen activated protein kinase (MAPK) pathway most often through KIAA1549-BRAF fusion, but also by other BRAF- or RAF1-gene fusions and point mutations (e.g. BRAFV600E). These features may serve as diagnostic and prognostic markers, and also facilitate development of targeted therapy. The aims of this study were to characterize the genetic alterations underlying the development of PA in six tumor cases, and evaluate methods for fusion oncogene detection. Using a combined analysis of RNA sequencing and copy number variation data we identified a new BRAF fusion involving the 5' gene fusion partner GTF2I (7q11.23), not previously described in PA. The new GTF2I-BRAF 19-10 fusion was found in one case, while the other five cases harbored the frequent KIAA1549-BRAF 16-9 fusion gene. Similar to other BRAF fusions, the GTF2I-BRAF fusion retains an intact BRAF kinase domain while the inhibitory N-terminal domain is lost. Functional studies on GTF2I-BRAF showed elevated MAPK pathway activation compared to BRAFWT. Comparing fusion detection methods, we found Fluorescence in situ hybridization with BRAF break apart probe as the most sensitive method for detection of different BRAF rearrangements (GTF2I-BRAF and KIAA1549-BRAF). Our finding of a new BRAF fusion in PA further emphasis the important role of B-Raf in tumorigenesis of these tumor types. Moreover, the consistency and growing list of BRAF/RAF gene fusions suggests these rearrangements to be informative tumor markers in molecular diagnostics, which could guide future treatment strategies.

  4. Genomic Deletions Correlate with Underexpression of Novel Candidate Genes at Six Loci in Pediatric Pilocytic Astrocytoma

    Directory of Open Access Journals (Sweden)

    Nicola Potter

    2008-08-01

    Full Text Available The molecular pathogenesis of pediatric pilocytic astrocytoma (PA is not well defined. Previous cytogenetic and molecular studies have not identified nonrandom genetic aberrations. To correlate differential gene expression and genomic copy number aberrations (CNAs in PA, we have used Affymetrix GeneChip HG_U133A to generate gene expression profiles of 19 pediatric patients and the SpectralChip 2600 to investigate CNAs in 11 of these tumors. Hierarchical clustering according to expression profile similarity grouped tumors and controls separately. We identified 1844 genes that showed significant differential expression between tumor and normal controls, with a large number clearly influencing phosphatidylinositol and mitogen-activated protein kinase signaling in PA. Most CNAs identified in this study were single-clone alterations. However, a small region of loss involving up to seven adjacent clones at 7q11.23 was observed in seven tumors and correlated with the underexpression of BCL7B. Loss of four individual clones was also associated with reduced gene expression including SH3GL2 at 9p21.2-p23, BCL7A (which shares 90% sequence homology with BCL7B at 12q24.33, DRD1IP at 10q26.3, and TUBG2 and CNTNAP1 at 17q21.31. Moreover, the down-regulation of FOXG1B at 14q12 correlated with loss within the gene promoter region in most tumors. This is the first study to correlate differential gene expression with CNAs in PA.

  5. Differential expression and methylation of brain developmental genes define location-specific subsets of pilocytic astrocytoma.

    Science.gov (United States)

    Lambert, Sally R; Witt, Hendrik; Hovestadt, Volker; Zucknick, Manuela; Kool, Marcel; Pearson, Danita M; Korshunov, Andrey; Ryzhova, Marina; Ichimura, Koichi; Jabado, Nada; Fontebasso, Adam M; Lichter, Peter; Pfister, Stefan M; Collins, V Peter; Jones, David T W

    2013-08-01

    Pilocytic astrocytomas (PAs) are the most common brain tumors in pediatric patients and can cause significant morbidity, including chronic neurological deficiencies. They are characterized by activating alterations in the mitogen-activated protein kinase pathway, but little else is known about their development. To map the global DNA methylation profiles of these tumors, we analyzed 62 PAs and 7 normal cerebellum samples using Illumina 450K microarrays. These data revealed two subgroups of PA that separate according to tumor location (infratentorial versus supratentorial), and identified key neural developmental genes that are differentially methylated between the two groups, including NR2E1 and EN2. Integration with transcriptome microarray data highlighted significant expression differences, which were unexpectedly associated with a strong positive correlation between methylation and expression. Differentially methylated probes were often identified within the gene body and/or regions up- or downstream of the gene, rather than at the transcription start site. We also identified a large number of differentially methylated genes between cerebellar PAs and normal cerebellum, which were again enriched for developmental genes. In addition, we found a significant association between differentially methylated genes and SUZ12 binding sites, indicating potential disruption of the polycomb repressor complex 2 (PRC2). Taken together, these data suggest that PA from different locations in the brain may arise from region-specific cells of origin, and highlight the potential disruption of key developmental regulators during tumorigenesis. These findings have implications for future basic research and clinical trials, as therapeutic targets and drug sensitivity may differ according to tumor location.

  6. Manganese superoxide dismutase (MnSOD) is a malignant astrocytoma specific biomarker and associated with adverse prognosis in p53 expressing glioblastoma.

    Science.gov (United States)

    Shwetha, Shivayogi D; Shastry, Arun H; Arivazhagan, Arimappamagan; Santosh, Vani

    2016-01-01

    Manganese super oxide dismutase (MnSOD) has been previously identified as one of the top regulated genes associated with poor survival in glioblastoma (GBM) patients. In the current study we have evaluated the protein expression of MnSOD across various grades of astrocytoma, studied its influence on survival of GBM patients and following recurrence. The protein expression of MnSOD was analyzed on tumor tissue sections by immunohistochemistry on 30 diffuse astrocytomas (DA), 50 anaplastic astrocytomas (AA), 30 paired (primary and recurrent) GBM samples and 30 non-tumor brain tissues. The protein expression among the different grades of diffusely infiltrating astrocytoma (DIA) was evaluated by Kruskal-Wallis one-way ANOVA followed by post hoc test. Wilcoxon matched pair test was employed to assess MnSOD protein expression across 30 paired GBM samples (primary and recurrent). The prognostic impact of MnSOD protein expression individually and following stratification with p53 expression was evaluated in a cohort of 123 GBM patients. Both over-all survival (OS) and progression free survival (PFS) analysis were performed by employing Cox regression analysis and Kaplan-Meier survival analysis on GBM patients. A significantly increased protein expression of MnSOD was observed among malignant astrocytomas (GBM and AA) in comparison with either DA or non-tumor brain tissues (pastrocytoma and GBM compared to low grade astrocytoma and control brain. An increase in MnSOD expression following GBM tumor recurrence strengthens its putative role in tumor aggressiveness. Further, MnSOD emerges as a poor prognostic biomarker in p53 expressing GBMs, rendering this molecule as a potential therapeutic target in such patients. Copyright © 2015 Elsevier GmbH. All rights reserved.

  7. Impact of Resection on Survival of Isocitrate Dehydrogenase 1-Mutated World Health Organization Grade II Astrocytoma After Malignant Progression.

    Science.gov (United States)

    Grau, Stefan J; Hampl, Juergen A; Kohl, Ann-Cathrin; Timmer, Marco; Duval, Inga V; Blau, Tobias; Ruge, Maximilian I; Goldbrunner, Roland H

    2017-07-01

    To evaluate the impact of surgical resection and adjuvant treatment on the course of patients after malignant progression of previously treated isocitrate dehydrogenase 1 (IDH1)-mutated World Health Organization (WHO) grade II astrocytoma. This retrospective study explored 56 patients undergoing tumor resection for malignant progression after previously treated IDH1-mutated WHO grade II astrocytoma. We analyzed survival after malignant progression, analyzed overall survival (OS), and identified prognostic factors using Kaplan-Meier estimates and log-rank test. By the time of malignant transformation, median age was 44 years, and median Karnofsky Performance Status (KPS) score was 90. Complete resection of contrast-enhancing tissue was achieved in 18 (32.1%) patients. Median survival after re-resection was 33 months (95% confidence interval [CI], 20-46); median OS was 123 months (95% CI, 77-170). Gross total tumor resection, postoperative KPS score ≥80, adjuvant radiochemotherapy, and prior radiotherapy significantly correlated with post-malignant progression survival. Patients in good clinical condition with malignant progression of previously treated low-grade gliomas should receive aggressive treatment, including re-resection. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Long-term daily temozolomide with dose-dependent efficacy in MGMT promotor methylation negative recurrent high-grade astrocytoma.

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    Zhou, Zhengqiu; Howard, Tracy A; Villano, John L

    2017-11-01

    Temozolomide (TMZ) for malignant gliomas is traditionally dosed in 5 out of a 28-day cycle, however alternative regimens exist, including dose-dense. Continuous daily dosing is available, but the acceptable dose and duration of therapy is unknown. We document a 40-year-old male with recurrent anaplastic astrocytoma, IDH mutant and MGMT promotor methylation negative, who has well-tolerated continuous daily TMZ for 20 months at 100 mg per day for nearly the length of this period. A trial at 80 mg per day demonstrated disease progression with response upon return to 100 mg per day. Prior to the daily TMZ, the patient underwent three surgical resections, radiation therapy with concurrent TMZ according to the EORTC-NCIC protocol, and subsequently bevacizumab in combination with use of the Optune device. Long-term survival of patients with recurrent malignant gliomas is uncommon, and currently no standard treatment strategies exist for these patients. We present this case to demonstrate the tolerability and dose dependency of prolonged daily TMZ dosing as a therapeutic option for recurrent anaplastic astrocytomas.

  9. Phytometabolite Dehydroleucodine Induces Cell Cycle Arrest, Apoptosis, and DNA Damage in Human Astrocytoma Cells through p73/p53 Regulation.

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    Natalia Bailon-Moscoso

    Full Text Available Accumulating evidence supports the idea that secondary metabolites obtained from medicinal plants (phytometabolites may be important contributors in the development of new chemotherapeutic agents to reduce the occurrence or recurrence of cancer. Our study focused on Dehydroleucodine (DhL, a sesquiterpene found in the provinces of Loja and Zamora-Chinchipe. In this study, we showed that DhL displayed cytostatic and cytotoxic activities on the human cerebral astrocytoma D384 cell line. With lactone isolated from Gynoxys verrucosa Wedd, a medicinal plant from Ecuador, we found that DhL induced cell death in D384 cells by triggering cell cycle arrest and inducing apoptosis and DNA damage. We further found that the cell death resulted in the increased expression of CDKN1A and BAX proteins. A marked induction of the levels of total TP73 and phosphorylated TP53, TP73, and γ-H2AX proteins was observed in D384 cells exposed to DhL, but no increase in total TP53 levels was detected. Overall these studies demonstrated the marked effect of DhL on the diminished survival of human astrocytoma cells through the induced expression of TP73 and phosphorylation of TP73 and TP53, suggesting their key roles in the tumor cell response to DhL treatment.

  10. Influence of insurance status and income in anaplastic astrocytoma: an analysis of 4325 patients.

    Science.gov (United States)

    Shin, Jacob Y; Yoon, Ja Kyoung; Diaz, Aidnag Z

    2017-03-01

    To determine the impact of insurance status and income for anaplastic astrocytoma (AA). Data were extracted from the National Cancer Data Base. Chi square test, Kaplan-Meier method, and Cox regression models were employed in SPSS 22.0 (Armonk, NY: IBM Corp.) for data analyses. 4325 patients with AA diagnosed from 2004 to 2013 were identified. 2781 (64.3%) had private insurance, 925 (21.4%) Medicare, 396 (9.2%) Medicaid, and 223 (5.2%) were uninsured. Those uninsured were more likely to be Black or Hispanic versus White or Asian (p < 0.001), have lower median income (p < 0.001), less educated (p < 0.001), and not receive adjuvant chemoradiation (p < 0.001). 1651 (38.2%) had income ≥$63,000, 1204 (27.8%) $48,000-$62,999, 889 (20.5%) $38,000-$47,999, and 581 (13.4%) had income <$38,000. Those with lower income were more likely to be Black or Hispanic versus White or Asian (p < 0.001), uninsured (p < 0.001), reside in a rural area (p < 0.001), less educated (p < 0.001), and not receive adjuvant chemoradiation (p < 0.001). Those with private insurance had significantly higher overall survival (OS) than those uninsured, on Medicaid, or on Medicare (p < 0.001). Those with income ≥$63,000 had significantly higher OS than those with lower income (p < 0.001). On multivariate analysis, age, insurance status, income, and adjuvant therapy were independent prognostic factors for OS. Being uninsured and having income <$38,000 were independent prognostic factors for worse OS in AA. Further investigations are warranted to help determine ways to ensure adequate medical care for those who may be socially disadvantaged so that outcome can be maximized for all patients regardless of socioeconomic status.

  11. A review of current and future treatment strategies for malignant astrocytomas in adults

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    Nieder, C. [Texas Univ., Houston, TX (United States). Dept. of Experimental Radiation Oncology; Nestle, U. [Universitaet des Saarlandes, Homburg/Saar (Germany). Radiologische Klinik

    2000-06-01

    This review discusses available laboratory and clinical data as well as recent advances in our knowledge about prognostic factors and their implications for the design of future clinical trials. Results: Elucidation of the biology of malignant astrocytomas allowed for development of rational new approaches, such as gene therapy and immunotherapy, which could interfere with established treatment regimens or being used independently. Possible strategies include the restoration of defective cancer-inhibitory genes, cell transduction or transfection with antisense DNA corresponding to genes coding for growth factors and their receptors, or with the so-called suicide genes. Several antiangiogenic approaches such as administration of thalidomide, protamine, or monoclonal antibodies against vascular endothelial growth factor have been developed, too. Further treatment possibilities include modulation of drug resistance, e.g. by P-glycoprotein antagonists or O6-alkyl-guanine-DNA-transferase inhibitors, inhibition of matrix metalloproteinases, inhibition of protein kinase C, and administration of agents such as phenylbutyrate or valproic acid that showed promising antiproliferative effects in vitro. Conclusions: Several rational new approaches are now entering clinical trials. In the light of limited survival after standard treatment it is recommended that patients should be offered participation in such trials. (orig.) [German] In dieser Arbeit werden sowohl die verfuegbaren Labor- und klinischen Daten als auch die aktuellen Fortschritte auf dem Gebiet prognostischer Faktoren und deren Bedeutung fuer das Design kuenftiger klinischer Studien diskutiert. Ergebnisse: Die Aufklaerung der Biologie dieser Tumoren ermoeglichte die Entwicklung rationaler neuer Strategien, zum Beispiel basierend auf der Gen- und Immuntherapie, die entweder zusammen mit etablierten Methoden oder allein anwendbar sind. Moegliche Strategien bestehen in der Wiederherstellung defekter

  12. CT and MR findings in pilocytic astrocytomas; Computertomographische und magnetresonanztomographische Befunde des pilozytischen Astrozytoms

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    Huber, G. [Universitaet des Saarlandes, Homburg/Saar (Germany). Abt. fuer Neuroradiologie; Glas, B. [Universitaet des Saarlandes, Homburg/Saar (Germany). Abt. fuer Neuroradiologie; Hermes, M. [Universitaet des Saarlandes, Homburg/Saar (Germany). Abt. fuer Neuroradiologie

    1997-02-01

    Purpose: In a retrospective study we examined the predilection sites, the CT and MR morphology and the contrast behaviour of intracranial pilocytic astrocytoma (PA) in a large number of patients. Material and methods: The study consists of 47 patients (18 male, 29 female, mean age 10.1 years) with histologically proven PA. Results: The chief predilection site turned out to be the hypothalamic region (15/47=32%). The other regions involved were (in descending order): Brain hemispheres 8/47=17%; cerebellar vermis 7/47=15%, cerebellar hemispheres; thalamic nuclei and pontomedullar region 4/47=8.5% each; pineal gland 2/47=4%; pons, lamina tecti and optic fascicle 1/47=2% each. The PA presented 24/47=51% cysts; 7/47=15% calcifications; 2/47=4% necrosis and 1/47=2% perifocal oedema. In three cases (3/47=6%) CT and MRI showed no contrast enhancement. Conclusion: PA appear in almost all brain regions but there is a clear preference of the hypothalamic region. PA of the hypothalamic region are a special subgroup. They are often associated with neurofibromatosis 1, tend to infiltrate surrounding structures, and to dissiminate into the intracranial and spinal subarachnoid space. (orig.) [Deutsch] Ziel: Retrospectiv sollen an einem groesseren Patientenklientel Praedilektionsorte, CT- und MR-Morphologie sowie das Kontrastmittelverhalten intrakranieller pilozytischer Astrozytome untersucht werden. Material und Methode: Die Studie stuetzt sich auf die CT- und MR-Befunde von 47 Patienten (18 m, 27 w) mit einem mittleren Alter von 10,1 Jahren, bei denen jeweils ein pilozytisches Astrozytom histologisch gesichert war. Ergebnisse: Als eindeutiger Praedilektionsort erwies sich die Hypothalamusregion (15/47=32%). Die Grosshirnhemisphaeren waren 8mal (8/47=17%), der Kleinhirnwurm 7mal (7/47=15%), die Kleinhirnhemisphaeren, das Thalamuskerngebiet und die pontomedullaere Region je 4mal (4/47=8,5%), die Glandula pinealis zweimal (2/47=4%), der Pons, die Lamina tecti und der Fasciculus

  13. Biocytin and biotin uptake into NB2a neuroblastoma and C6 astrocytoma cells.

    Science.gov (United States)

    Baur, Barbara; Suormala, Terttu; Baumgartner, E Regula

    2002-01-25

    Uptake of biocytin and biotin was investigated in cultured transformed variants of neuronal (NB2a neuroblastoma) and glial (C6 astrocytoma) CNS cells. NB2a cells took up both compounds but biocytin was transported more efficiently than biotin in the nanomolar concentration range. In NB2a cells a single transport mechanism was found for biocytin with different kinetic parameters in the presence of high extracellular Na+ (Km 0.4 microM, Vmax 20 pmol/min/mg), K+ (Km 1.7 microM, Vmax 32 pmol/min/mg), or choline+ (Km 0.1 microM, Vmax 5 pmol/min/mg). Two transport systems (Km1 17 microM, Vmax1 53 pmol/min/mg; Km2 314 microM, Vmax2 360 pmol/min/mg) were identified for biotin with only system 1 being Na+-dependent. Biocytin uptake was competitively inhibited by excess biotin but not vice versa. Inhibition studies with structural analogs indicated different specificities for biotin and biocytin uptake. Biocytin uptake into C6 cells was hardly detectable whereas biotin was taken up by diffusion (kD 0.6 microl/min/mg) and a single saturable mechanism (Km 70 microM, Vmax 119 pmol/min/mg) at high extracellular Na+. High extracellular K+ enhanced biotin diffusion into C6 cells. Inhibition studies with structural analogs revealed a less specific biotin uptake mechanism in C6 than in NB2a cells. Biocytin normalized deficient biotin-dependent propionyl-CoA carboxylase activity within 4 h in biotin-deficient NB2a cells whereas in C6 cells reactivation was biocytin is only poorly transported into C6 cells. Specific biocytin uptake into NB2a cells is to our knowledge the first demonstration of a carrier-mediated transport mechanism for this compound. Neuronal biocytin uptake might contribute to the pathogenesis of biotinidase deficiency where biocytin is present in elevated levels.

  14. A case of an epithelioid glioblastoma with the BRAF V600E mutation colocalized with BRAF intact low-grade diffuse astrocytoma.

    Science.gov (United States)

    Kuroda, Jun-Ichiro; Nobusawa, Sumihito; Nakamura, Hideo; Yokoo, Hideaki; Ueda, Ryuta; Makino, Keishi; Yano, Shigetoshi; Kuratsu, Jun-ichi

    2016-04-01

    Epithelioid glioblastomas are one of the rarest histological variants of glioblastomas, which are not formally recognized by the World Health Organization (WHO) classification. Epithelioid glioblastomas usually occur as primary lesions, but there have been several reports of secondary epithelioid glioblastomas or epithelioid glioblastomas with pre- or co-existing lesions to date. The serine/threonine-protein kinase B-Raf (BRAF) V600E mutation has been found at a high frequency of 54% in epithelioid glioblastomas. We present a case of a 26-year-old female patient with an epithelioid glioblastoma with the BRAF V600E mutation in her right frontal lobe. In the present case, a low-grade diffuse astrocytoma component had colocalized with the epithelioid glioblastoma. The component presented prominent calcification on neuroimages as well as by histology, and low-grade diffuse astrocytoma was considered to be a precursor lesion of an epithelioid glioblastoma. However, the BRAF V600E mutation was detected only in epithelioid glioblastoma but not in low-grade diffuse astrocytoma. To the best of our knowledge, this is the first report demonstrating a discrepancy in the BRAF V600E mutation states between epithelioid glioblastoma and colocalized low-grade astrocytoma. © 2015 Japanese Society of Neuropathology.

  15. miR-106a-5p inhibits the proliferation and migration of astrocytoma cells and promotes apoptosis by targeting FASTK.

    Directory of Open Access Journals (Sweden)

    Feng Zhi

    Full Text Available Astrocytomas are common malignant intracranial tumors that comprise the majority of adult primary central nervous system tumors. MicroRNAs (miRNAs are small, non-coding RNAs (20-24 nucleotides that post-transcriptionally modulate gene expression by negatively regulating the stability or translational efficiency of their target mRNAs. In our previous studies, we found that the downregulation of miR-106a-5p in astrocytomas is associated with poor prognosis. However, its specific gene target(s and underlying functional mechanism(s in astrocytomas remain unclear. In this study, we used mRNA microarray experiments to measure global mRNA expression in the presence of increased or decreased miR-106a-5p levels. We then performed bioinformatics analysis based on multiple target prediction algorithms to obtain candidate target genes that were further validated by computational predictions, western blot analysis, quantitative real-time PCR, and the luciferase reporter assay. Fas-activated serine/threonine kinase (FASTK was identified as a direct target of miR-106a-5p. In human astrocytomas, miR-106a-5p is downregulated and negatively associated with clinical staging, whereas FASTK is upregulated and positively associated with advanced clinical stages, at both the protein and mRNA levels. Furthermore, Kaplan-Meier analysis revealed that the reduced expression of miR-106a-5p or the increased expression of FASTK is significantly associated with poor survival outcome. These results further supported the finding that FASTK is a direct target gene of miR-106a-5p. Next, we explored the function of miR-106a-5p and FASTK during astrocytoma progression. Through gain-of-function and loss-of-function studies, we demonstrated that miR-106a-5p can significantly inhibit cell proliferation and migration and can promote cell apoptosis in vitro. The knockdown of FASTK induced similar effects on astrocytoma cells as those induced by the overexpression of miR-106a-5p. These

  16. PROX1 is a novel pathway-specific prognostic biomarker for high-grade astrocytomas; results from independent glioblastoma cohorts stratified by age and IDH mutation status.

    Science.gov (United States)

    Roodakker, Kenney R; Elsir, Tamador; Edqvist, Per-Henrik D; Hägerstrand, Daniel; Carlson, Joseph; Lysiak, Malgorzata; Henriksson, Roger; Pontén, Fredrik; Rosell, Johan; Söderkvist, Peter; Stupp, Roger; Tchougounova, Elena; Nistér, Monica; Malmström, Annika; Smits, Anja

    2016-11-08

    PROX1 is a transcription factor with an essential role in embryonic development and determination of cell fate. In addition, PROX1 has been ascribed suppressive as well as oncogenic roles in several human cancers, including brain tumors. In this study we explored the correlation between PROX1 expression and patient survival in high-grade astrocytomas. For this purpose, we analyzed protein expression in tissue microarrays of tumor samples stratified by patient age and IDH mutation status. We initially screened 86 unselected high-grade astrocytomas, followed by 174 IDH1-R132H1 immunonegative glioblastomas derived from patients aged 60 years and older enrolled in the Nordic phase III trial of elderly patients with newly diagnosed glioblastoma. Representing the younger population of glioblastomas, we studied 80 IDH-wildtype glioblastomas from patients aged 18-60 years. There was no correlation between PROX1 protein and survival for patients with primary glioblastomas included in these cohorts. In contrast, high expression of PROX1 protein predicted shorter survival in the group of patients with IDH-mutant anaplastic astrocytomas and secondary glioblastomas. The prognostic impact of PROX1 in IDH-mutant 1p19q non-codeleted high-grade astrocytomas, as well as the negative findings in primary glioblastomas, was corroborated by gene expression data extracted from the Cancer Genome Atlas. We conclude that PROX1 is a new prognostic biomarker for 1p19q non-codeleted high-grade astrocytomas that have progressed from pre-existing low-grade tumors and harbor IDH mutations.

  17. miR-101 reverses hypomethylation of the PRDM16 promoter to disrupt mitochondrial function in astrocytoma cells.

    Science.gov (United States)

    Lei, Qianqian; Liu, Xiaoping; Fu, Haijuan; Sun, Yingnan; Wang, Liping; Xu, Gang; Wang, Wei; Yu, Zhibin; Liu, Changhong; Li, Peiyao; Feng, Jianbo; Li, Guiyuan; Wu, Minghua

    2016-01-26

    Our previous report identified PR domain containing 16 (PRDM16), a member of the PR-domain gene family, as a new methylation associated gene in astrocytoma cells. This previous study also reported that miR-101 is a tumor suppressor in glioma. The present study confirms that PRDM16 is a hypomethylated gene that can be overexpressed in astrocytoma patients and demonstrates that the hypomethylation status of the PRDM16 promoter can predict poor prognoses for astrocytoma patients. The results reported herein show that PRDM16 was inhibited by miR-101 directly and also through epigenetic regulation. PRDM16 was confirmed as a new target of miR-101 and shown to be directly inhibited by miR-101. miR-101 also decreased the expression of PRDM16 by altering the methylation status of the PRDM16 promoter. miR-101 was associated with a decrease in the methylation-related histones H3K4me2 and H3K27me3 and an increase in H3K9me3 and H4K20me3 on the PRDM16 promoter. In addition, EZH2, EED and DNMT3A were identified as direct targets of miR-101, and miR-101 suppressed PRDM16 expression by targeting DNMT3A which decreases histone H3K27me3 and H3K4me2 at the PRDM16 core promoter. The results reported here demonstrate that miR-101 disrupted cellular mitochondrial function and induced cellular apoptosis via the mitochondrial pathway; for example, MMP and ATP levels decreased, while there was an increase in ADP/ATP ratios and ROS levels, levels of cleaved Caspase-9 and cleaved-PARP, the Bax/Bcl-2 ratios, and Smac release from the mitochondria to the cytoplasm. Knockdown of PRDM16 reversed the anti-apoptotic effect of miR-101 inhibition. In summary, miR-101 reversed the hypomethylation of the PRDM16 promoter which suppressed the expression of PRDM16, disrupted cellular mitochondrial function, and induced cellular apoptosis.

  18. [Hemorrhagic Onset of Subependymal Giant Cell Astrocytoma Associated with Tuberous Sclerosis:A Case Report and Review of Literature].

    Science.gov (United States)

    Adachi, Masayo; Nakamura, Michio; Shinozaki, Natsuki; Miyazaki, Tadashi

    2017-05-01

    We report on a case of subependymal giant cell astrocytoma(SEGA)in a patient with tuberous sclerosis(TSC)that presented with intratumoral hemorrhage and acute hydrocephalus. Initial treatment was external ventricular drainage to control the intracranial pressure;however, the tumor increased in size due to recurrent hemorrhage. Subsequently, the tumor was successfully removed via the transcortical-transventricular approach without neurological deterioration. Although intratumoral hemorrhage is extremely rare in patients with SEGA, subsequent acute hydrocephalus resulting from obstruction of the foramen of Monro will be fatal if prompt surgical treatment is not available. Careful and periodical radiographic examination of the central nervous system will be mandatory in patients with TSC, especially in those who have subependymal nodules(SEN)or SEGA around the foramen of Monro. Radical surgical removal should be considered before they become symptomatic.

  19. Anaplastic oligo-astrocytoma occurring after resection of a cerebral cavernous malformation; malignant transformation? Case report and review on etiology.

    Science.gov (United States)

    Schreuder, Tobien; Te Lintelo, Merijn; Kubat, Bela; Koehler, Peter

    2010-03-01

    We report a 71-year-old woman who presented with a cerebral cavernous malformation in the right frontal lobe for which she underwent total resection. Three years later, she was admitted with seizures and neuroimaging revealed a partially calcified lesion in the area of the earlier cavernous malformation, consistent with a residual malformation. A few months later she presented with cognitive decline and neuroimaging now revealed a large mass lesion in the same area as the cavernous malformation, irregularly enhancing, spreading through the corpus callosum to the left frontal lobe. Histological examination showed an anaplastic oligo-astrocytoma. These findings suggest that cerebral cavernous malformations, or at least a subgroup, have the potential for oligodendrocytic and astrocytic transformation. Various hypotheses to explain the etiology of these rare cases are discussed.

  20. Spontaneous Involution of a Non-Optic Astrocytoma in Neurofibromatosis Type I: Serial Magnetic Resonance Imaging Evaluation

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    Cakirer, S. [Istanbul Sisli Etfal Hospital (Turkey). Dept. of Radiology; Karaarslan, E. [VKV American Hospital, Istanbul (Turkey). Dept. of Radiology

    2004-10-01

    A patient with neurofibromatosis type I (NF1) was followed-up with serial magnetic resonance imaging (MRI) studies over a period of 6 years. A contrast-enhancing lesion of the internal capsule, histologically proven to be pilocytic astrocytoma through stereotactic brain biopsy with mass effect and associated edema, was detected to reveal spontaneous involution on follow-up MRI studies. Although spontaneous regression of gliomas of the optic pathway-hypothalamus in patients with NF1 is relatively common in the literature, spontaneous involution of non-optic (i.e. areas other than optic pathways and hypothalamus) gliomas is rarely reported. Conservative management with follow-up MRI studies should be considered for non-optic glial tumors and tumor-like masses in patients with NF1, and surgical treatment should not be considered unless the lesions exhibit a rapid or unrelenting growth on serial MRI studies or produce significant clinical deterioration.

  1. Binding of NIR-conPK and NIR-6T to astrocytomas and microglial cells: evidence for a protein related to TSPO.

    Directory of Open Access Journals (Sweden)

    Michelle Sexton

    Full Text Available PK 11195 and DAA1106 bind with high-affinity to the translocator protein (TSPO, formerly known as the peripheral benzodiazepine receptor. TSPO expression in glial cells increases in response to cytokines and pathological stimuli. Accordingly, [(11C]-PK 11195 and [(11C]-DAA1106 are recognized molecular imaging (MI agents capable of monitoring changes in TSPO expression occurring in vivo and in response to various neuropathologies.Here we tested the pharmacological characteristics and TSPO-monitoring potential of two novel MI agents: NIR-conPK and NIR-6T. NIR-conPK is an analogue of PK 11195 conjugated to the near-infrared (NIR emitting fluorophore: IRDye 800CW. NIR-6T is a DAA1106 analogue also conjugated to IRDye 800CW.We found that NIR-6T competed for [(3H]-PK 11195 binding in astrocytoma cell homogenates with nanomolar affinity, but did not exhibit specific binding in intact astrocytoma cells in culture, indicating that NIR-6T is unlikely to constitute a useful MI agent for monitoring TSPO expression in intact cells. Conversely, we found that NIR-conPK did not compete for [(3H]-PK 11195 binding in astrocytoma cell homogenate, but exhibited specific binding in intact astrocytoma cells in culture with nanomolar affinity, suggesting that NIR-conPK binds to a protein distinct, but related to, TSPO. Accordingly, treating intact astrocytoma cells and microglia in culture with cytokines led to significant changes in the amount of NIR-conPK specific binding without corresponding change in TSPO expression. Remarkably, the cytokine-induced changes in the protein targeted by NIR-conPK in intact microglia were selective, since IFN-gamma (but not TNFalpha and TGFbeta increased the amount of NIR-conPK specific binding in these cells.Together these results suggest that NIR-conPK binds to a protein that is related to TSPO, and expressed by astrocytomas and microglia. Our results also suggest that the expression of this protein is increased by specific

  2. Paradoxical role of 3-methyladenine in pyocyanin-induced toxicity in 1321N1 astrocytoma and SH-SY5Y neuroblastoma cells.

    Science.gov (United States)

    McFarland, Amelia J; Grant, Gary D; Perkins, Anthony V; Flegg, Cameron; Davey, Andrew K; Allsopp, Tristan J; Renshaw, Gillian; Kavanagh, Justin; McDermott, Catherine M; Anoopkumar-Dukie, Shailendra

    2013-01-01

    The role of autophagy in pyocyanin (PCN)-induced toxicity in the central nervous system (CNS) remains unclear, with only evidence from our group identifying it as a mechanism underlying toxicity in 1321N1 astrocytoma cells. Therefore, the aim of this study was to further examine the role of autophagy in PCN-induced toxicity in the CNS. To achieve this, we exposed 1321N1 astrocytoma and SH-SY5Y neuroblastoma cells to PCN (0-100 μmol/L) and tested the contribution of autophagy by measuring the impact of the autophagy inhibitor 3-methyladenine (3-MA) using a series of biochemical and molecular markers. Pretreatment of 1321N1 astrocytoma cells with 3-MA (5 mmol/L) decreased the PCN-induced acidic vesicular organelle and autophagosome formation as measured using acridine orange and green fluorescent protein-LC3 -LC3 fluorescence, respectively. Furthermore, 3-MA (5 mmol/L) significantly protected 1321N1 astrocytoma cells against PCN-induced toxicity. In contrast pretreatment with 3-MA (5 mmol/L) increased PCN-induced toxicity in SH-SY5Y neuroblastoma cells. Given the influence of autophagy in inflammatory responses, we investigated whether the observed effects in this study involved inflammatory mediators. The PCN (100 μmol/L) significantly increased the production of interleukin-8 (IL-8), prostaglandin E2 (PGE₂), and leukotriene B4 (LTB₄) in both cell lines. Consistent with its paradoxical role in modulating PCN-induced toxicity, 3-MA (5 mmol/L) significantly reduced the PCN-induced production of IL-8, PGE₂, and LTB₄ in 1321N1 astrocytoma cells but augmented their production in SH-SY5Y neuroblastoma cells. In conclusion, we show here for the first time the paradoxical role of autophagy in mediating PCN-induced toxicity in 1321N1 astrocytoma and SH-SY5Y neuroblastoma cells and provide novel evidence that these actions may be mediated by effects on IL-8, PGE₂, and LTB₄ production.

  3. Cathepsin L silencing increases As2O3 toxicity in malignantly transformed pilocytic astrocytoma MPA58 cells by activating caspases 3/7.

    Science.gov (United States)

    Primon, Monika; Huszthy, Peter C; Motaln, Helena; Talasila, Krishna M; Miletic, Hrvoje; Atai, Nadia A; Bjerkvig, Rolf; Lah Turnšek, Tamara

    2017-07-01

    Low-grade, pilocytic astrocytomas are treated by resection, but additional therapy is necessary for those tumors with anaplastic features. Arsenic trioxide (As2O3) is emerging as an effective chemotherapeutic agent for treatment of malignant glioblastoma multiforme, where Cathepsin L silencing enables lower, less harmful As2O3 concentrations to achieve the desired cytotoxic effect. Here, we evaluated the effects of As2O3 combined with stable Cathepsin L shRNA silencing on cell viability/metabolic activity, and apoptosis in primary cultures of recurrent malignantly transformed pilocytic astrocytoma (MPA). These cells expressed high Cathepsin L levels, and when grown as monolayers and spheroids, they were more resistant to As2O3 than the U87MG glioblastoma cell line. Caspases 3/7 activity in MPA58 spheroids was not significantly affected by As2O3, possibly due to higher chemoresistance of primary biopsy tissue of less malignant astrocytoma versus the malignant U87MG cell line. However, As2O3 treatment was cytotoxic to MPA spheroids after silencing of Cathepsin L expression. While Cathepsin L silencing only slightly decreased the live/dead cell ratio in As2O3-treated MPA-si spheroids under our experimental conditions, there was an increase in As2O3-mediated apoptosis in MPA-si spheroids, as indicated by elevated caspases 3/7 activity. Therefore, Cathepsin L silencing by gene manipulation can be applied when a more aggressive approach is needed in treatment of pilocytic astrocytomas with anaplastic features. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Pre-surgical integration of FMRI and DTI of the sensorimotor system in transcortical resection of a high-grade insular astrocytoma

    Directory of Open Access Journals (Sweden)

    Chelsea eEkstrand

    2016-03-01

    Full Text Available Herein we report on a patient with a WHO Grade III astrocytoma in the right insular region in close proximity to the internal capsule who underwent a right frontotemporal craniotomy. Total gross resection of insular gliomas remains surgically challenging based on the possibility of damage to the corticospinal tracts. However, maximizing the extent of resection has been shown to decrease future adverse outcomes. Thus, the goal of such surgeries should focus on maximizing extent of resection while minimizing possible adverse outcomes. In this case, pre-surgical planning included integration of functional magnetic resonance imaging (fMRI and diffusion tensor imaging (DTI, to localize motor and sensory pathways. Novel fMRI tasks were individually developed for the patient to maximize both somatosensory and motor activation simultaneously in areas in close proximity to the tumor. Information obtained was used to optimize resection trajectory and extent, facilitating gross total resection of the astrocytoma. Across all three motor-sensory tasks administered, fMRI revealed an area of interest just superior and lateral to the astrocytoma. Further, DTI analyses showed displacement of the corona radiata around the superior dorsal surface of the astrocytoma, extending in the direction of the activation found using fMRI. Taking into account these results, a transcortical superior temporal gyrus surgical approach was chosen in order to avoid the area of interest identified by fMRI and DTI. Total gross resection was achieved and minor post-surgical motor and sensory deficits were temporary. This case highlights the utility of comprehensive pre-surgical planning, including fMRI and DTI, to maximize surgical outcomes on a case-by-case basis.

  5. Noninvasive Assessment ofIDHMutational Status in World Health Organization Grade II and III Astrocytomas Using DWI and DSC-PWI Combined with Conventional MR Imaging.

    Science.gov (United States)

    Xing, Z; Yang, X; She, D; Lin, Y; Zhang, Y; Cao, D

    2017-06-01

    Isocitrate dehydrogenase ( IDH ) has been shown to have both diagnostic and prognostic implications in gliomas. The purpose of this study was to examine whether DWI and DSC-PWI combined with conventional MR imaging could noninvasively predict IDH mutational status in World Health Organization grade II and III astrocytomas. We retrospectively reviewed DWI, DSC-PWI, and conventional MR imaging in 42 patients with World Health Organization grade II and III astrocytomas. Minimum ADC, relative ADC, and relative maximum CBV values were compared between IDH -mutant and wild-type tumors by using the Mann-Whitney U test. Receiver operating characteristic curve and logistic regression were used to assess their diagnostic performances. Minimum ADC and relative ADC were significantly higher in IDH -mutated grade II and III astrocytomas than in IDH wild-type tumors ( P IDH mutation provided a sensitivity, specificity, positive predictive value, and negative predictive value of 100.0%, 60.9%, 85.6%, and 100.0%, respectively. A combination of DWI, DSC-PWI, and conventional MR imaging for the identification of IDH mutations resulted in a sensitivity, specificity, positive predictive value, and negative predictive value of 92.3%, 91.3%, 96.1%, and 83.6%. A combination of conventional MR imaging, DWI, and DSC-PWI techniques produces a high sensitivity, specificity, positive predictive value, and negative predictive value for predicting IDH mutations in grade II and III astrocytomas. The strategy of using advanced, semiquantitative MR imaging techniques may provide an important, noninvasive, surrogate marker that should be studied further in larger, prospective trials. © 2017 by American Journal of Neuroradiology.

  6. Low-Grade Astrocytoma Mutations in IDH1, P53, and ATRX Cooperate to Block Differentiation of Human Neural Stem Cells via Repression of SOX2

    Directory of Open Access Journals (Sweden)

    Aram S. Modrek

    2017-10-01

    Full Text Available Summary: Low-grade astrocytomas (LGAs carry neomorphic mutations in isocitrate dehydrogenase (IDH concurrently with P53 and ATRX loss. To model LGA formation, we introduced R132H IDH1, P53 shRNA, and ATRX shRNA into human neural stem cells (NSCs. These oncogenic hits blocked NSC differentiation, increased invasiveness in vivo, and led to a DNA methylation and transcriptional profile resembling IDH1 mutant human LGAs. The differentiation block was caused by transcriptional silencing of the transcription factor SOX2 secondary to disassociation of its promoter from a putative enhancer. This occurred because of reduced binding of the chromatin organizer CTCF to its DNA motifs and disrupted chromatin looping. Our human model of IDH mutant LGA formation implicates impaired NSC differentiation because of repression of SOX2 as an early driver of gliomagenesis. : In a human neural stem cell model of low-grade astrocytoma, Modrek et al. show that mutant IDH1 and loss of P53 and ATRX together block differentiation via disassociation of SOX2 from putative enhancers. This occurs because of disruption of chromatin looping secondary to hypermethylation at CTCF motifs. Keywords: low-grade glioma, astrocytoma, IDH, P53, ATRX, neural stem cells, SOX2, chromatin looping, CTCF, DNA methylation

  7. Targeting the MAP kinase pathway in astrocytoma cells using a recombinant anthrax lethal toxin as a way to inhibit cell motility and invasion.

    Science.gov (United States)

    Al-Dimassi, Saleh; Salloum, Gilbert; Saykali, Bechara; Khoury, Oula; Liu, Shihui; Leppla, Stephen H; Abi-Habib, Ralph; El-Sibai, Mirvat

    2016-05-01

    Malignant astrocytomas are highly invasive into adjacent and distant regions of the normal brain. Understanding and targeting cancer cell invasion is an important therapeutic approach. Cell invasion is a complex process that replies on many signaling pathways including the mitogen-activated protein (MAP) kinase (MAPK). In many cell lines, the use of MAPK-targeted drugs proved to be a potential method to inhibit cancer cell motility. In the present study, we use a recombinant anthrax lethal toxin (LeTx), which selectively inhibits the MAPK pathway, in order to target invasion. LeTx proved ineffective on cell survival in astrocytoma (as well as normal cells). However, astrocytoma cells that were treated with LeTx showed a significant decrease in cell motility as seen by wound healing as well as random 2D motility in serum. The cells also showed a decrease in invasion across a collagen matrix. The effect of LeTx on cell migration was mediated though the deregulation of Rho GTPases, which play a role in cell motility. Finally, the effect of LeTx on cell migration and Rho GTPases was mimicked by the inhibition of the MAPK pathway. In this study, we describe for the first time the effect of the LeTx on cancer cell motility and invasion not cell survival making it a potentially selective brain tumor invasion inhibitor.

  8. Immediate disappearance of hemifacial spasm after partial removal of ponto-medullary junction anaplastic astrocytoma: case report.

    Science.gov (United States)

    Castiglione, Melina; Broggi, Morgan; Cordella, Roberto; Acerbi, Francesco; Ferroli, Paolo

    2015-04-01

    Hemifacial spasm (HFS) is generally caused by a neurovascular conflict (NC) at the root exit zone (REZ) of the facial nerve at the brainstem. Although a direct compression to the seventh cranial nerve (CN) by the anterior inferior cerebellar artery (AICA) is generally the most frequent cause, secondary HFS may be related to other pathological conditions. HFS due to an intracranial mass lesion is exceptionally rare and it has been reported in very few cases. The online database was searched for English-language articles reporting cases of HFS due to brainstem mass lesions and the possible pathophysiological mechanisms involved in its genesis. A 47-year-old man affected by an anaplastic astrocytoma of the brainstem at the level of the ponto-medullary junction developed right HFS. He underwent a subtotal surgical removal of the tumor with complete resolution of the HFS. This is the ninth reported case of HFS caused by an intrinsic brainstem tumor. The exceptional rarity of the relationship between intra-axial tumors and peripheral HFS was analyzed.

  9. Emotional Functioning and School Contentment in Adolescent Survivors of Acute Myeloid Leukemia, Infratentorial Astrocytoma, and Wilms Tumor.

    Science.gov (United States)

    Jóhannsdóttir, Inga M; Moum, Torbjørn; Hjermstad, Marianne J; Wesenberg, Finn; Hjorth, Lars; Schrøder, Henrik; Lähteenmäki, Päivi M; Jónmundsson, Gudmundur; Loge, Jon H

    2011-09-01

    Purpose: Cancer in childhood may disrupt normal developmental processes and cause psychosocial problems in adolescent survivors of childhood cancers (ACCSs). Previous studies report inconsistent findings. Study aims were to assess subjective well-being (SWB), psychological distress, and school contentment in survivors of three dissimilar childhood cancers. Patients and methods: Nordic patients treated for acute myeloid leukemia (AML), infratentorial astrocytoma (IA), and Wilms tumor (WT) in childhood from 1985 to 2001, aged ≥1 year at diagnosis, and aged 13-18 years at the time of study were eligible for this questionnaire-based survey that included items on SWB, psychological distress, school contentment, self-esteem, and personality traits; 65% (151/231) responded. An age-equivalent group from a Norwegian health survey (n=7910) served as controls. Results: The median age of ACCSs was 16 years; 52% were males. ACCSs reported better SWB (p=0.004) and self-esteem (pself-esteem. However, ACCSs reported higher levels of psychological distress (p=0.002), mostly attributable to general worrying. No significant differences in outcomes were found across diagnoses, and time since diagnosis did not significantly affect the results. Conclusion: The overall emotional functioning of ACCSs was good, possibly due to changes in their perception of well-being after having survived a life-threatening disease. However, they seemed more worried than their peers. This may cause an additional strain at a vulnerable period in life.

  10. Pan-mutant IDH1 inhibitor BAY 1436032 for effective treatment of IDH1 mutant astrocytoma in vivo.

    Science.gov (United States)

    Pusch, Stefan; Krausert, Sonja; Fischer, Viktoria; Balss, Jörg; Ott, Martina; Schrimpf, Daniel; Capper, David; Sahm, Felix; Eisel, Jessica; Beck, Ann-Christin; Jugold, Manfred; Eichwald, Viktoria; Kaulfuss, Stefan; Panknin, Olaf; Rehwinkel, Hartmut; Zimmermann, Katja; Hillig, Roman C; Guenther, Judith; Toschi, Luisella; Neuhaus, Roland; Haegebart, Andrea; Hess-Stumpp, Holger; Bauser, Markus; Wick, Wolfgang; Unterberg, Andreas; Herold-Mende, Christel; Platten, Michael; von Deimling, Andreas

    2017-04-01

    Mutations in codon 132 of isocitrate dehydrogenase (IDH) 1 are frequent in diffuse glioma, acute myeloid leukemia, chondrosarcoma and intrahepatic cholangiocarcinoma. These mutations result in a neomorphic enzyme specificity which leads to a dramatic increase of intracellular D-2-hydroxyglutarate (2-HG) in tumor cells. Therefore, mutant IDH1 protein is a highly attractive target for inhibitory drugs. Here, we describe the development and properties of BAY 1436032, a pan-inhibitor of IDH1 protein with different codon 132 mutations. BAY 1436032 strongly reduces 2-HG levels in cells carrying IDH1-R132H, -R132C, -R132G, -R132S and -R132L mutations. Cells not carrying IDH mutations were unaffected. BAY 1436032 did not exhibit toxicity in vitro or in vivo. The pharmacokinetic properties of BAY 1436032 allow for oral administration. In two independent experiments, BAY 1436032 has been shown to significantly prolong survival of mice intracerebrally transplanted with human astrocytoma carrying the IDH1R132H mutation. In conclusion, we developed a pan-inhibitor targeting tumors with different IDH1R132 mutations.

  11. The sarin-like organophosphorus agent bis(isopropyl methyl)phosphonate induces ER stress in human astrocytoma cells.

    Science.gov (United States)

    Arima, Yosuke; Shiraishi, Hiroaki; Saito, Atsushi; Yoshimoto, Kanji; Namera, Akira; Makita, Ryosuke; Murata, Kazuhiro; Imaizumi, Kazunori; Nagao, Masataka

    2016-01-01

    Organophosphorus (OP) compounds such as sarin are toxic agents that irreversibly inhibit the enzyme acetylcholinesterase. A recent study showed that OP compounds also have multiple toxicity mechanisms, and another suggested that endoplasmic reticulum (ER) dysfunction contributes to OP toxicity. However, the signaling pathway and mechanisms involved are poorly understood. We examined whether the sarin-like OP agent bis(isopropyl methyl)phosphonate (BIMP), which exhibits toxicity similar to that of sarin, induced ER stress in human astrocytoma CCF-STTG1 cells. Our results demonstrate that BIMP exposure reduced cell viability. Moreover, it induced changes in mitochondrial membrane potential and increased cleavage of caspase 3. Treatment with BIMP increased the mRNA levels of the ER stress marker genes binding immunoglobulin protein (BiP) and the transcription factor C/EBP homologous protein (CHOP). Furthermore, BIMP increased the protein expressions and phosphorylation of BiP, CHOP, and protein kinase RNA-like ER kinase and the phosphorylation of eukaryotic translation initiation factor 2. Compared to BIMP treatment alone, pretreatment with the CHOP siRNA, siCHOP, decreased BIMP-dependent CHOP expression and improved CCF-STTG1 cell viability. Our findings suggest that BIMP induced mitochondrial dysfunction and apoptotic cell death event mediated by ER stress in CCF-STTG1 cells and that treatment targeted at managing ER stress has the potential to attenuate the toxicity of OP nerve agents.

  12. Concurrent TERT promoter and BRAF V600E mutation in epithelioid glioblastoma and concomitant low-grade astrocytoma.

    Science.gov (United States)

    Matsumura, Nozomi; Nakajima, Nozomi; Yamazaki, Tatsuya; Nagano, Takuro; Kagoshima, Kaie; Nobusawa, Sumihito; Ikota, Hayato; Yokoo, Hideaki

    2017-02-01

    Epithelioid glioblastoma (E-GBM) is a rare variant of glioblastoma (GBM), characterized by epithelioid cells with eosinophilic round cytoplasm devoid of stellate cytoplasmic processes. A number of studies have demonstrated that more than half of E-GBMs harbor a valine to glutamic acid substitution at position 600 of the serine/threonine-protein kinase BRAF (BRAF V600E). However, there are no previous reports on E-GBM with telomerase reverse transcriptase (TERT) promoter mutation in addition to BRAF V600E mutation. Here, we report an E-GBM case in an 18-year-old man with BRAF V600E and TERT promoter mutations. The tumor composed of 80% E-GBM and 20% diffuse astrocytoma-like components, and BRAF V600E and TERT promoter mutations were detected in both. E-GBM generally arises as a primary lesion; however, a few previous cases have been demonstrated to accompany low-grade areas. Demonstration of concurrent BRAF V600E and TERT promoter mutations in low- and high-grade lesions strongly suggested their identical origin, and acquisition of each mutation may be an early event, possibly playing a pivotal role in the genesis and subsequent progression to E-GBM. © 2016 Japanese Society of Neuropathology.

  13. HIV-1 Gp120 clade B/C induces a GRP78 driven cytoprotective mechanism in astrocytoma

    Science.gov (United States)

    López, Sheila N.; Rodríguez-Valentín, Madeline; Rivera, Mariela; Rodríguez, Maridaliz; Babu, Mohan; Cubano, Luis A.; Xiong, Huangui; Wang, Guangdi; Kucheryavykh, Lilia; Boukli, Nawal M.

    2017-01-01

    HIV-1 clades are known to be one of the key factors implicated in modulating HIV-associated neurocognitive disorders. HIV-1 B and C clades account for the majority of HIV-1 infections, clade B being the most neuropathogenic. The mechanisms behind HIV-mediated neuropathogenesis remain the subject of active research. We hypothesized that HIV-1 gp120 clade B and C proteins may exert differential proliferation, cell survival and NeuroAIDS effects in human astrocytoma cells via the Unfolded Protein Response, an endoplasmic reticulum- based cytoprotective mechanism. The differential effect of gp120 clade B and C was evaluated using for the first time a Tandem Mass Tag isobaric labeling quantitative proteomic approach. Flow cytometry analyses were performed for cell cycle and cell death identification. Among the proteins differentiated by HIV-1 gp120 proteins figure cytoskeleton, oxidative stress, UPR markers and numerous glycolytic metabolism enzymes. Our results demonstrate that HIV-1 gp120 B induced migration, proliferative and protective responses granted by the expression of GRP78, while HIV-1 gp120 C induced the expression of key inflammatory and pro-apoptotic markers. These novel findings put forward the first evidence that GRP78 is a key player in HIV-1 clade B and C neuropathogenic discrepancies and can be used as a novel target for immunotherapies. PMID:28978127

  14. Presurgical Administration of mTOR Inhibitors in Patients with Large Subependymal Giant Cell Astrocytoma Associated with Tuberous Sclerosis Complex.

    Science.gov (United States)

    Jiang, Tao; Du, Jiang; Raynald; Wang, Junmei; Li, Chunde

    2017-11-01

    Direct surgical resection remains the standard treatment for patients with tuberous sclerosis complex (TSC) with a large subependymal giant cell astrocytoma (SEGA). Rapamycin or everolimus is seldom used in these patients because of the risk of increased intracranial pressure and possibility of sudden death. Three patients with TSC and a large intracranial SEGA received oral rapamycin (0.5 mg/day) or everolimus (2.5 mg/day) before surgery for tumor resection. After mTOR inhibitor therapy, computed tomography scans and magnetic resonance imaging revealed tumor reduction. Tumor bleeding was easy to control during surgery, and the border between tumor and surrounding brain tissue was clearly differentiated. Analysis of postsurgical tumor specimens showed low blood density and focal necrosis. Preoperative mTOR inhibitors could be a potentially novel treatment modality in large TSC-SEGA with hydrocephalus. In this series, mTOR inhibitors were not only safe and well tolerated, but also beneficial for tumor resection. Copyright © 2017. Published by Elsevier Inc.

  15. Serial changes in lymphocyte subsets in patients with newly diagnosed high grade astrocytomas treated with standard radiation and temozolomide.

    Science.gov (United States)

    Campian, Jian L; Piotrowski, Anna F; Ye, Xiaobu; Hakim, Frances T; Rose, Jeremy; Yan, Xiao-Yi; Lu, Yao; Gress, Ronald; Grossman, Stuart A

    2017-11-01

    The immune system plays a significant role in cancer prevention and outcome. In high grade astrocytomas (HGA), severe lymphopenia is associated with shortened survival due to tumor progression. This study was performed to quantify serial changes in lymphocyte subsets in HGA following standard radiation (RT) and temozolomide (TMZ). Adults (KPS >60, HIV negative) with newly diagnosed HGA scheduled to receive concurrent RT and TMZ and adjuvant TMZ were eligible. Blood was collected before beginning concurrent RT/TMZ and at weeks 6, 10, 18, and 26, and 3 months after completing adjuvant TMZ. Lymphocyte subsets were analyzed by flow cytometry. Twenty patients (70% glioblastoma, median age 53, 50% male, 80% Caucasian) who enrolled from January 2014 to August 2014 were followed until April 2016. Baseline dexamethasone dose was 0.5 mg/day and 15% had absolute lymphocyte counts (ALC) <1000 cells/mm3 before starting RT/TMZ. However, 75% developed lymphopenia with ALC <1000 cells/mm3 after completion of RT/TMZ. NK cells, B cells and all T lymphocytes subsets dropped significantly after concurrent RT/TMZ and remained depressed for the 48 weeks of observation. The CD4+/CD8+ ratio was not affected significantly during follow-up. Severe lymphopenia involving all subsets occurred early in treatment and remained present for nearly 1 year. To our knowledge, this is the first report of serial trends in lymphocyte subsets following standard RT and TMZ for HGA.

  16. A Case of Therapy-Related Acute Myeloid Leukemia Associated with Adjuvant Temozolomide Chemotherapy for Anaplastic Astrocytoma.

    Science.gov (United States)

    Kosugi, Kenzo; Saito, Katsuya; Takahashi, Wataru; Tokuda, Yukina; Tomita, Hideyuki

    2017-05-01

    Temozolomide (TMZ) is now standard adjuvant therapy in combination with radiotherapy for patients with newly diagnosed malignant glioma. Treatment-related myelodysplastic syndrome and acute treatment-related leukemia (t-AML) associated with TMZ chemotherapy for patients with glioma is quite a rare complication. A 43-year-old man with an anaplastic astrocytoma received radiation therapy synchronized with ranimustine and adjuvant TMZ chemotherapy for 15 cycles. Close follow-up magnetic resonance imaging of the head during TMZ chemotherapy showed no evidence of tumor progression. One year after the completion of TMZ chemotherapy, a bone-marrow aspiration was performed because the patient's white blood cell count decreased. He was diagnosed with t-AML based on the bone marrow examination, and then he was referred to the cancer center for the treatment of t-AML. In this case study, we continued adjuvant TMZ therapy beyond the recommended 6 cycles. Currently, there is no consensus as to how long the adjuvant TMZ therapy should be continued for the treatment of residual tumor showing no apparent interval change. A new decision-making tool to assess the clinical benefits against the side effects for long-term adjuvant TMZ therapy is needed. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. A fraction of neurofibromin interacts with PML bodies in the nucleus of the CCF astrocytoma cell line

    Energy Technology Data Exchange (ETDEWEB)

    Godin, Fabienne; Villette, Sandrine; Vallee, Beatrice; Doudeau, Michel; Morisset-Lopez, Severine [Centre de Biophysique Moleculaire, Centre National de la Recherche Scientifique (CNRS), UPR 4301, Universite d' Orleans et INSERM, rue Charles Sadron, 45071 Orleans Cedex 2 (France); Ardourel, Maryvonne; Hevor, Tobias [Laboratoire de Neurobiologie, Universite d' Orleans, BP 6759, 45067 Orleans Cedex 2 (France); Pichon, Chantal [Centre de Biophysique Moleculaire, Centre National de la Recherche Scientifique (CNRS), UPR 4301, Universite d' Orleans et INSERM, rue Charles Sadron, 45071 Orleans Cedex 2 (France); Benedetti, Helene, E-mail: helene.benedetti@cnrs-orleans.fr [Centre de Biophysique Moleculaire, Centre National de la Recherche Scientifique (CNRS), UPR 4301, Universite d' Orleans et INSERM, rue Charles Sadron, 45071 Orleans Cedex 2 (France)

    2012-02-24

    Highlights: Black-Right-Pointing-Pointer We validate the use of specific anti-Nf1 antibodies for immunofluorescence studies. Black-Right-Pointing-Pointer We detect Nf1 in the cytoplasm and nucleus of CCF cells. Black-Right-Pointing-Pointer We demonstrate that Nf1 partially colocalizes with PML nuclear bodies. Black-Right-Pointing-Pointer We demonstrate that there is a direct interaction between a fraction of Nf1 and the PML bodies. -- Abstract: Neurofibromatosis type 1 is a common genetic disease that causes nervous system tumors, and cognitive deficits. It is due to mutations within the NF1 gene, which encodes the Nf1 protein. Nf1 has been shown to be involved in the regulation of Ras, cAMP and actin cytoskeleton dynamics. In this study, using immunofluorescence experiments, we have shown a partial nuclear localization of Nf1 in the astrocytoma cell line: CCF and we have demonstrated that Nf1 partially colocalizes with PML (promyelocytic leukemia) nuclear bodies. A direct interaction between Nf1 and the multiprotein complex has further been demonstrated using 'in situ' proximity ligation assay (PLA).

  18. Expression of Telomeres in Astrocytoma WHO Grade 2 to 4: TERRA Level Correlates with Telomere Length, Telomerase Activity, and Advanced Clinical Grade12

    Science.gov (United States)

    Sampl, Sandra; Pramhas, Sibylle; Stern, Christian; Preusser, Matthias; Marosi, Christine; Holzmann, Klaus

    2012-01-01

    Cancer cells bypass replicative senescence, the major barrier to tumor progression, by using telomerase or alternative lengthening of telomeres (ALT) as telomere maintenance mechanisms (TMMs). Correlation between ALT and patient survival was demonstrated for high-grade astrocytomas. Transcription from subtelomeres produces telomeric repeat-containing RNA (TERRA), a natural inhibitor of telomerase activity (TA). This led us to evaluate correlations of TERRA and TMM with tumor grade and outcome in astrocytoma patients. SYBR Green real-time reverse transcription-polymerase chain reaction assays for quantitation of total and chromosome 2p and 18p specific TERRA levels were developed. Tumor samples from 46 patients with astrocytoma grade 2 to 4, tissue controls, and cell lines were assessed. TMMs were evaluated by measuring TA and by detecting long telomeres due to ALT. In glioblastoma multiforme (GBM) grade 4, total TERRA levels were similar to cell lines but 14-, 31-, and 313-fold lower compared with grade 3, grade 2, and nonmalignant tissue, respectively. Total TERRA levels differed from chromosomal levels. Low 2p TERRA levels correlated with dense promoter methylation of subtelomeric CpG islands, indicating that TERRA expression in gliomas may be chromosome specific and epigenetically regulated. Total TERRA levels correlated with diagnosis, with low or absent TA and the presence of ALT, and were tentatively associated with favorable patient prognosis in our cohort (P = .06). TA and short telomeres identified a subset of GBM with a median survival of only 14.8 months. TERRA and TA may be prognostic in astrocytic tumors. PMID:22348177

  19. Expression of telomeres in astrocytoma WHO grade 2 to 4: TERRA level correlates with telomere length, telomerase activity, and advanced clinical grade.

    Science.gov (United States)

    Sampl, Sandra; Pramhas, Sibylle; Stern, Christian; Preusser, Matthias; Marosi, Christine; Holzmann, Klaus

    2012-02-01

    Cancer cells bypass replicative senescence, the major barrier to tumor progression, by using telomerase or alternative lengthening of telomeres (ALT) as telomere maintenance mechanisms (TMMs). Correlation between ALT and patient survival was demonstrated for high-grade astrocytomas. Transcription from subtelomeres produces telomeric repeat-containing RNA (TERRA), a natural inhibitor of telomerase activity (TA). This led us to evaluate correlations of TERRA and TMM with tumor grade and outcome in astrocytoma patients. SYBR Green real-time reverse transcription-polymerase chain reaction assays for quantitation of total and chromosome 2p and 18p specific TERRA levels were developed. Tumor samples from 46 patients with astrocytoma grade 2 to 4, tissue controls, and cell lines were assessed. TMMs were evaluated by measuring TA and by detecting long telomeres due to ALT. In glioblastoma multiforme (GBM) grade 4, total TERRA levels were similar to cell lines but 14-, 31-, and 313-fold lower compared with grade 3, grade 2, and nonmalignant tissue, respectively. Total TERRA levels differed from chromosomal levels. Low 2p TERRA levels correlated with dense promoter methylation of subtelomeric CpG islands, indicating that TERRA expression in gliomas may be chromosome specific and epigenetically regulated. Total TERRA levels correlated with diagnosis, with low or absent TA and the presence of ALT, and were tentatively associated with favorable patient prognosis in our cohort (P = .06). TA and short telomeres identified a subset of GBM with a median survival of only 14.8 months. TERRA and TA may be prognostic in astrocytic tumors.

  20. Post-treatment changes of tumour perfusion parameters can help to predict survival in patients with high-grade astrocytoma

    Energy Technology Data Exchange (ETDEWEB)

    Sanz-Requena, Roberto; Marti-Bonmati, Luis [Hospital Quironsalud Valencia, Radiology Department, Valencia (Spain); Hospital Universitari i Politecnic La Fe, Grupo de Investigacion Biomedica en Imagen, Valencia (Spain); Revert-Ventura, Antonio J.; Salame-Gamarra, Fares [Hospital de Manises, Radiology Department, Manises (Spain); Garcia-Marti, Gracian [Hospital Quironsalud Valencia, Radiology Department, Valencia (Spain); Hospital Universitari i Politecnic La Fe, Grupo de Investigacion Biomedica en Imagen, Valencia (Spain); CIBER-SAM, Instituto de Salud Carlos III, Madrid (Spain); Perez-Girbes, Alexandre [Hospital Universitari i Politecnic La Fe, Grupo de Investigacion Biomedica en Imagen, Valencia (Spain); Molla-Olmos, Enrique [Hospital La Ribera, Radiology Department, Alzira (Spain)

    2017-08-15

    Vascular characteristics of tumour and peritumoral volumes of high-grade gliomas change with treatment. This work evaluates the variations of T2*-weighted perfusion parameters as overall survival (OS) predictors. Forty-five patients with histologically confirmed high-grade astrocytoma (8 grade III and 37 grade IV) were included. All patients underwent pre- and post-treatment T2*-weighted contrast-enhanced magnetic resonance (MR) imaging. Tumour, peritumoral and control volumes were segmented. Relative variations of cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), K{sup trans-T2*}, k{sub ep-T2*}, v{sub e-T2*} and v{sub p-T2*} were calculated. Differences regarding tumour grade and surgical resection extension were evaluated with ANOVA tests. For each parameter, two groups were defined by non-supervised clusterisation. Survival analysis were performed on these groups. For the tumour region, the 90th percentile increase or stagnation of CBV was associated with shorter survival, while a decrease related to longer survival (393 ± 189 vs 594 ± 294 days; log-rank p = 0.019; Cox hazard-ratio, 2.31; 95% confidence interval [CI], 1.12-4.74). K{sup trans-T2*} showed similar results (414 ± 177 vs 553 ± 312 days; log-rank p = 0.037; hazard-ratio, 2.19; 95% CI, 1.03-4.65). The peritumoral area values showed no relationship with OS. Post-treatment variations of the highest CBV and K{sup trans-T2*} values in the tumour volume are predictive factors of OS in patients with high-grade gliomas. (orig.)

  1. The extrinsic and intrinsic apoptotic pathways are involved in manganese toxicity in rat astrocytoma C6 cells.

    Science.gov (United States)

    Alaimo, Agustina; Gorojod, Roxana M; Kotler, Mónica L

    2011-08-01

    Manganese (Mn) is a trace element known to be essential for maintaining the proper function and regulation of many biochemical and cellular reactions. However, chronic exposure to high levels of Mn in occupational or environmental settings can lead to its accumulation in the brain resulting in a degenerative brain disorder referred to as Manganism. Astrocytes are the main Mn store in the central nervous system and several lines of evidence implicate these cells as major players in the role of Manganism development. In the present study, we employed rat astrocytoma C6 cells as a sensitive experimental model for investigating molecular mechanisms involved in Mn neurotoxicity. Our results show that C6 cells undergo reactive oxygen species-mediated apoptotic cell death involving caspase-8 and mitochondrial-mediated pathways in response to Mn. Exposed cells exhibit typical apoptotic features, such as chromatin condensation, cell shrinkage, membrane blebbing, caspase-3 activation and caspase-specific cleavage of the endogenous substrate poly (ADP-ribose) polymerase. Participation of the caspase-8 dependent pathway was assessed by increased levels of FasL, caspase-8 activation and Bid cleavage. The involvement of the mitochondrial pathway was demonstrated by the disruption of the mitochondrial membrane potential, the opening of the mitochondrial permeability transition pore, cytochrome c release, caspase-9 activation and the increased mitochondrial levels of the pro-apoptotic Bcl-2 family proteins. In addition, our data also shows for the first time that mitochondrial fragmentation plays a relevant role in Mn-induced apoptosis. Taking together, these findings contribute to a deeper elucidation of the molecular signaling mechanisms underlying Mn-induced apoptosis. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. Methylmercury alters glutathione homeostasis by inhibiting glutaredoxin 1 and enhancing glutathione biosynthesis in cultured human astrocytoma cells.

    Science.gov (United States)

    Robitaille, Stephan; Mailloux, Ryan J; Chan, Hing Man

    2016-08-10

    Methylmercury (MeHg) is a neurotoxin that binds strongly to thiol residues on protein and low molecular weight molecules like reduced glutathione (GSH). The mechanism of its effects on GSH homeostasis particularly at environmentally relevant low doses is not fully known. We hypothesized that exposure to MeHg would lead to a depletion of reduced glutathione (GSH) and an accumulation of glutathione disulfide (GSSG) leading to alterations in S-glutathionylation of proteins. Our results showed exposure to low concentrations of MeHg (1μM) did not significantly alter GSH levels but increased GSSG levels by ∼12-fold. This effect was associated with a significant increase in total cellular glutathione content and a decrease in GSH/GSSG. Immunoblot analyses revealed that proteins involved in glutathione synthesis were upregulated accounting for the increase in cellular glutathione. This was associated an increase in cellular Nrf2 protein levels which is required to induce the expression of antioxidant genes in response to cellular stress. Intriguingly, we noted that a key enzyme involved in reversing protein S-glutathionylation and maintaining glutathione homeostasis, glutaredoxin-1 (Grx1), was inhibited by ∼50%. MeHg treatment also increased the S-glutathionylation of a high molecular weight protein. This observation is consistent with the inhibition of Grx1 and elevated H2O2 production however; contrary to our original hypothesis we found few S-glutathionylated proteins in the astrocytoma cells. Collectively, MeHg affects multiple arms of glutathione homeostasis ranging from pool management to protein S-glutathionylation and Grx1 activity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Association between the growth rate of subependymal giant cell astrocytoma and age in patients with tuberous sclerosis complex.

    Science.gov (United States)

    Tsai, Jeng-Dau; Wei, Chang-Ching; Tsao, Teng-Fu; Hsiao, Yu-Ping; Tsai, Henry J; Yang, Sheng-Hui; Tsai, Min-Ling; Sheu, Ji-Nan

    2016-01-01

    The most common neurological complications associated with tuberous sclerosis complex (TSC) include intractable seizures that begin in infancy and subependymal giant cell astrocytoma (SEGA) complicated by hydrocephalus with increasing age. Information on SEGA growth of TSC patients is limited. This study aimed to examine the TSC-SEGA growth rates by periodic neuroimaging. This study evaluated the TSC-SEGA growth rates by serial neuroimaging. Fifty-eight patients with TSC underwent systematic evaluation, including a review of medical history and serial brain neuroimaging. While magnetic resonance imaging was more sensitive in detecting cortical tubers than computed tomography (73.1 vs. 0 %, p < 0.001), its efficacy in identifying intracranial lesions was comparable to that of computed tomography (96.2 vs. 100 %, p = 0.658). Significant tumor growth was observed in children (p = 0.012) and adults (p = 0.028) during follow-up periods, respectively (median for children 23.5 months, interquartile range 18-40 months and median for adults 23 months, interquartile range 12-34 months). Further, the SEGA growth rate in children was significantly higher than that in adults (75.6 vs. 16.5 %, p = 0.03). The results of the study show that SEGA has a significantly higher growth rate in children using serial follow-up brain imaging, suggesting the importance of performing follow-up neuroimaging at yearly intervals in childhood to identify and prevent potential comorbidities.

  4. Unique findings of subependymal giant cell astrocytoma within cortical tubers in patients with tuberous sclerosis complex: a histopathological evaluation.

    Science.gov (United States)

    Katz, Joel S; Frankel, Hyman; Ma, Tracy; Zagzag, David; Liechty, Benjamin; Zeev, Bruria Ben; Tzadok, Michal; Devinsky, Orrin; Weiner, Howard L; Roth, Jonathan

    2017-04-01

    Tuberous sclerosis is associated with three central nervous system pathologies: cortical/subcortical tubers, subependymal nodules (SENs), and subependymal giant cell astrocytomas (SEGAs). Tubers are associated with epilepsy, which is often medication-resistant and often leads to resective surgery. Recently, mammalian target of rapamycin inhibitors (mTORi) have been shown to be effective reducing seizure burden in some patients with tuberous sclerosis complex (TSC)-related refractory epilepsy. mTORi have also been shown to be an alternative for surgery treating SEGAs. We describe several cases of resected tubers that contained SEGA tissue without an intraventricular SEGA. After institutional review board (IRB) protocol approval, we retrospectively reviewed the surgical-pathological data for all TSC patients who underwent cortical resections for treatment of refractory epilepsy at NYU Langone Medical Center and Tel Aviv Medical Center between 2003 and 2013. Data included demographics, epilepsy type, MRI characteristics, epilepsy outcome, and histopathological staining. We reviewed cortical resections from 75 patients with complete pathological studies. In three patients, cortical lesions demonstrated histopathological findings consistent with a SEGA within the resected tuber tissue, with no intraventricular SEGA. All lesions were cortically based and none had any intraventricular extension. No patient had been treated before surgery with an mTORi. Two of the three patients remain Engel grade I-II. All lesions stained positive for glial fibrillary acidic protein (GFAP), synaptophysin, and neuronal nuclear antigen (NeuN). This is the first description of cortical tubers harboring SEGA tissue. This observation though preliminary may suggest a subgroup of patients with intractable epilepsy in whom mTORi may be considered before surgical intervention.

  5. Differentiation of hemangioblastomas from pilocytic astrocytomas using 3-T magnetic resonance perfusion-weighted imaging and MR spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    She, D.J.; Xing, Z.; Zeng, Z.; Cao, D.R. [First Affiliated Hospital of Fujian Medical University, Department of Radiology, Fuzhou, Fujian (China); Shang, X.Y. [University of California, San Diego, Department of Medicine and the Moores UCSD Cancer Center, La Jolla, CA (United States)

    2015-03-01

    Hemangioblastomas and pilocytic astrocytomas (PAs) present similar imaging features on conventional MR imaging, making differential diagnosis a challenge. The purpose of this study was to evaluate the usefulness of dynamic susceptibility-weighted contrast-enhanced perfusion-weighted imaging (DSC-PWI) and proton MR spectroscopic imaging in the differentiation of hemangioblastomas and PAs. A 3.0-T MR imaging unit was used to perform DSC-PWI and conventional MR imaging on 14 patients with hemangioblastomas and 22 patients with PAs. Four patients with hemangioblastomas and 10 PA patients also underwent proton MR spectroscopy. Parameters of relative peak height (rPH) and relative percentage of signal intensity recovery (rPSR) were acquired by DSC-PWI and variables of N-acetylaspasrtate (NAA)/creatine (Cr), choline (Cho)/Cr, and lactate-lipid (Lac-Lip)/Cr by MR spectroscopy. The sensitivity, specificity, and the area under the receiver operating characteristic curve of all analyzed parameters at respective cutoff values were determined. Higher rPH but lower rPSR values were detected in hemangioblastomas compared to PAs. The NAA/Cr ratio was significantly lower in hemangioblastomas compared with PAs. The threshold values ≥3.2 for rPH provide sensitivity, specificity, positive predictive values, and negative predictive values of 85.7, 95.5, 92.3, and 91.3 %, respectively, for differentiating hemangioblastomas from PAs. The optimal threshold values were ≤0.9 for rPSR and ≤1.5 for NAA/Cr ratios in tumor. Significantly higher rPH and lower NAA/Cr were seen in patients with hemangioblastomas when compared with PA patients, suggesting that DSC-PWI and proton MR spectroscopy are helpful in the characterization and differentiation of these two types of tumors. (orig.)

  6. The impact of concurrent temozolomide with adjuvant radiation and IDH mutation status among patients with anaplastic astrocytoma.

    Science.gov (United States)

    Kizilbash, Sani H; Giannini, Caterina; Voss, Jesse S; Decker, Paul A; Jenkins, Robert B; Hardie, John; Laack, Nadia N; Parney, Ian F; Uhm, Joon H; Buckner, Jan C

    2014-10-01

    This study assesses the controversial role of temozolomide (TMZ) concurrent with adjuvant radiation (RT) in patients with anaplastic astrocytoma (AA). The impact of isocitrate dehydrogenase (IDH) status on therapy and outcomes is also examined. All adult patients diagnosed with AA from 2001 to 2011 and treated with standard doses of adjuvant RT were identified retrospectively for clinical data extraction. IDH status was determined by IDH1-R132H immunostain and sequencing for other mutations in IDH1/IDH2. Cumulative survival probabilities were estimated using the Kaplan-Meier method. Cox proportional hazards regression models were fit for univariable/multivariable analyses. 136 patients had received concurrent TMZ while 29 had not. Of these, IDH status was determined on 114 and 27 patients, respectively. On univariable analysis, improved five-year survival was independently associated with concurrent TMZ (46.2 vs. 29.3%, p = 0.02) and IDH mutation (78.9 vs. 22.0%, p IDH mutation was additionally associated with a greater likelihood of extensive resection possibly secondary to a more favorable tumor location. Gross total/subtotal resections also led to improved survival when compared to biopsy alone on univariable analysis. On multivariable analysis, the association with five-year survival persisted for both concurrent TMZ and IDH mutation, but not with extent of surgery. Both IDH mutation and concurrent TMZ are associated with improved five-year survival in patients with AA who are receiving adjuvant RT. Secondarily, the association between five-year survival and extent of resection is lost on multivariable analysis. This suggests a possible association between IDH mutation, tumor location and consequent resectability.

  7. Mechanisms of U87 astrocytoma cell uptake and trafficking of monomeric versus protofibril Alzheimer's disease amyloid-β proteins.

    Directory of Open Access Journals (Sweden)

    Yali Li

    Full Text Available A significant hallmark of Alzheimer's disease is the formation of senile plaques in the brain due to the unbalanced levels of amyloid-beta (Aβ. However, although how Aβ is produced from amyloid precursor proteins is well understood, little is known regarding the clearance and metabolism of various Aβ aggregates from the brain. Similarly, little is known regarding how astrocytes internalize and degrade Aβ, although astrocytes are known to play an important role in plaque maintenance and Aβ clearance. The objective of this study is to investigate the cellular mechanisms that mediate the internalization of soluble monomeric versus oligomeric Aβ by astrocytes. We used a combination of laser confocal microscopy and genetic and pharmacological experiments to dissect the internalization of sAβ42 and oAβ42 and their postendocytic transport by U87 human brain astrocytoma cell line. Both Aβ42 species were internalized by U87 cells through fluid phase macropinocytosis, which required dynamin 2. Depleting LDL receptor-related protein 1 (LRP1 decreased sAβ42 uptake more significantly than that of oAβ42. We finally show that both Aβ42 species were rapidly transported to lysosomes through an endolytic pathway and subjected to proteolysis after internalization, which had no significant toxic effects to the U87 cells under relatively low concentrations. We propose that macropinocytic sAβ42 and oAβ42 uptake and their subsequent proteolytic degradation in astroglial cells is a significant mechanism underlying Aβ clearance from the extracellular milieu. Understanding the molecular events involved in astrocytic Aβ internalization may identify potential therapeutic targets for Alzheimer's disease.

  8. Mammalian Target of Rapamycin Inhibitor Induced Complete Remission of a Recurrent Subependymal Giant Cell Astrocytoma in a Patient Without Features of Tuberous Sclerosis Complex.

    Science.gov (United States)

    Appalla, Deepika; Depalma, Andres; Calderwood, Stanley

    2016-07-01

    The majority of patients with subependymal giant cell astrocytoma (SEGA) have tuberous sclerosis complex (TSC). In such patients, the mammalian target of rapamycin (mTOR) inhibitor everolimus has been shown to induce responses. Isolated SEGA have been reported in patients without clinical or genetic features of TSC. The treatment of these patients with everolimus has not previously been reported. We treated a patient with a recurrent isolated SEGA with an mTOR inhibitor. The patient tolerated therapy well and had a sustained complete remission. MTOR inhibitors may be useful for the treatment of isolated SEGA. Further study is warranted. © 2016 Wiley Periodicals, Inc.

  9. Somatic BRAF c.1799T>A p.V600E Mosaicism syndrome characterized by a linear syringocystadenoma papilliferum, anaplastic astrocytoma, and ocular abnormalities.

    Science.gov (United States)

    Watanabe, Yuko; Shido, Kosuke; Niihori, Tetsuya; Niizuma, Hidetaka; Katata, Yu; Iizuka, Chie; Oba, Daiju; Moriya, Kunihiko; Saito-Nanjo, Yuka; Onuma, Masaei; Rikiishi, Takeshi; Sasahara, Yoji; Watanabe, Mika; Aiba, Setsuya; Saito, Ryuta; Sonoda, Yukihiko; Tominaga, Teiji; Aoki, Yoko; Kure, Shigeo

    2016-01-01

    Genetic mosaicism for somatic mutations of oncogenes is common in genodermatoses, which can be complicated with extra-cutaneous abnormalities. Here we describe an infant with a congenital anaplastic astrocytoma, a linear syringocystadenoma papilliferum, and ocular abnormalities. The BRAF c.1799T>A p.V600E mutation was detected in both the brain and skin tumor cells but not in the blood or normal skin cells, suggesting somatic mosaicsism for the mutation. Clinically, the brain tumor gradually became life threatening without any response to conventional chemotherapies including carboplatin, etoposide, and temozolomide. Vemurafenib, a BRAF p.V600E inhibitor, was administered daily after the detection of the BRAF mutation. This single-agent therapy was dramatically effective against the anaplastic astrocytoma; the tumor regressed, the cerebrospinal fluid cell count and protein levels decreased to normal levels, and hydrocephalus resolved. Moreover, other lesions including a corneal cyst also responded to vemurafenib. The brain tumor continued shrinking after 6 months of treatment. We present a genodermatosis syndrome associated with BRAF c.1799T>A p.V600E mosaicism. This syndrome may represent a new entity in the mosaic RASopathies, partly overlapping with Schimmelpenning-Feuerstein-Mims syndrome, which is driven by mosaicism of HRAS and/or KRAS activating mutations. Screening for BRAF c.1799T>A p.V600E is especially useful for those with malignant tumors, because it is one of the most-druggable targets. © 2015 Wiley Periodicals, Inc.

  10. Hydrogen sulfide generation from l-cysteine in the human glioblastoma-astrocytoma U-87 MG and neuroblastoma SHSY5Y cell lines.

    Science.gov (United States)

    Bronowicka-Adamska, Patrycja; Bentke, Anna; Wróbel, Maria

    2017-01-01

    Hydrogen sulfide (H2S) is endogenously synthesized from l-cysteine in reactions catalyzed by cystathionine beta-synthase (CBS, EC 4.2.1.22) and gamma-cystathionase (CSE, EC 4.4.1.1). The role of 3-mercaptopyruvate sulfurtransferase (MPST, EC 2.8.1.2) in H2S generation is also considered; it could be important for tissues with low CTH activity, e.g. cells of the nervous system. The expression and activity of CBS, CTH, and MPST were detected in the human glioblastoma-astrocytoma (U-87 MG) and neuroblastoma (SHSY5Y) cell lines. In both cell lines, the expression and activity of MPST were the highest among the investigated enzymes, suggesting its possible role in the generation of H2S. The RP-HPLC method was used to determine the concentration of cystathionine and alpha-ketobutyrate, products of the CBS- and CTH-catalyzed reactions. The difference in cystathionine levels between cell homogenates treated with totally CTH-inhibiting concentrations of dl-propargylglycine and without the inhibitor was used to evaluate the activity of CBS. The higher expression and activity of CBS, CTH and MPST in the neuroblastoma cells were associated with more intensive generation of H2S in the presence of 2 mM cysteine. A threefold higher level of sulfane sulfur, a potential source of hydrogen sulfide, was detected in the astrocytoma cells in comparison to the neuroblastoma cells.

  11. Improving accuracy in astrocytomas grading by integrating a robust least squares mapping driven support vector machine classifier into a two level grade classification scheme.

    Science.gov (United States)

    Glotsos, Dimitris; Kalatzis, Ioannis; Spyridonos, Panagiota; Kostopoulos, Spiros; Daskalakis, Antonis; Athanasiadis, Emmanouil; Ravazoula, Panagiota; Nikiforidis, George; Cavouras, Dionisis

    2008-06-01

    Grading of astrocytomas is an important task for treatment planning; however, it suffers from significantly great inter-observer variability. Computer-assisted diagnosis systems have been propose to assist towards minimizing subjectivity, however, these systems present either moderate accuracy or utilize specialized staining protocols and grading systems that are difficult to apply in daily clinical practice. The present study proposes a robust mathematical formulation by integrating state-of-art technologies (support vector machines and least squares mapping) in a cascade classification scheme for separating low from high and grade III from grade IV astrocytic tumours. Results have indicated that low from high-grade tumours can be correctly separated with a certainty as high as 97.3%, whereas grade III from grade IV tumours with 97.8%. The overall performance was 95.2%. These high rates have been a result of applying the least squares mapping technique to features prior to classification. A significant byproduct of least squares mapping is that the number of support vectors of the SVM classifiers dropped dramatically from about 80% when no mapping was used to less than 5% when mapping was used. The latter is a clear indication that the SVM classifier has a greater potential to generalize well to new data. In this way, digital image analysis systems for automated grading of astrocytomas are brought closer to clinical practice.

  12. Decreased survival of glioma patients with astrocytoma grade IV (glioblastoma multiforme) associated with long-term use of mobile and cordless phones.

    Science.gov (United States)

    Carlberg, Michael; Hardell, Lennart

    2014-10-16

    On 31 May 2011 the WHO International Agency for Research on Cancer (IARC) categorised radiofrequency electromagnetic fields (RF-EMFs) from mobile phones, and from other devices that emit similar non-ionising electromagnetic fields, as a Group 2B, i.e., a "possible", human carcinogen. A causal association would be strengthened if it could be shown that the use of wireless phones has an impact on the survival of glioma patients. We analysed survival of 1678 glioma patients in our 1997-2003 and 2007-2009 case-control studies. Use of wireless phones in the >20 years latency group (time since first use) yielded an increased hazard ratio (HR) = 1.7, 95% confidence interval (CI) = 1.2-2.3 for glioma. For astrocytoma grade IV (glioblastoma multiforme; n = 926) mobile phone use yielded HR = 2.0, 95% CI = 1.4-2.9 and cordless phone use HR = 3.4, 95% CI = 1.04-11 in the same latency category. The hazard ratio for astrocytoma grade IV increased statistically significant per year of latency for wireless phones, HR = 1.020, 95% CI = 1.007-1.033, but not per 100 h cumulative use, HR = 1.002, 95% CI = 0.999-1.005. HR was not statistically significant increased for other types of glioma. Due to the relationship with survival the classification of IARC is strengthened and RF-EMF should be regarded as human carcinogen requiring urgent revision of current exposure guidelines.

  13. High-Definition Fiber Tractography in Evaluation and Surgical Planning of Thalamopeduncular Pilocytic Astrocytomas in Pediatric Population: Case Series and Review of Literature.

    Science.gov (United States)

    Celtikci, Emrah; Celtikci, Pinar; Fernandes-Cabral, David Tiago; Ucar, Murat; Fernandez-Miranda, Juan Carlos; Borcek, Alp Ozgun

    2017-02-01

    Thalamopeduncular tumors (TPTs) of childhood present a challenge for neurosurgeons due to their eloquent location. Preoperative fiber tracking provides total or near-total resection, without additional neurologic deficit. High-definition fiber tractography (HDFT) is an advanced white matter imaging technique derived from magnetic resonance imaging diffusion data, shown to overcome the limitations of diffusion tensor imaging. We aimed to investigate alterations of corticospinal tract (CST) and medial lemniscus (ML) caused by TPTs and to demonstrate the application of HDFT in preoperative planning. Three pediatric patients with TPTs were enrolled. CSTs and MLs were evaluated for displacement, infiltration, and disruption. The relationship of these tracts to tumors was identified and guided surgical planning. Literature was reviewed for publications on pediatric thalamic and TPTs that used diffusion imaging. Two patients had histologic diagnosis of pilocytic astrocytoma. One patient whose imaging suggested a low-grade glioma was managed conservatively. All tracts were displaced (1 CST anteriorly, 2 CSTs, 1 ML anteromedially, 1 ML medially, and 1 ML posteromedially). Literature review revealed 2 publications with 15 pilocytic astrocytoma cases, which investigated CST only. The condition of sensory pathway or anteromedial displacement of the CST in these tumors was not reported previously. Displacement patterns of the perilesional fiber bundles by TPTs are not predictable. Fiber tracking, preferably HDFT, should be part of preoperative planning to achieve maximal extent of resection for longer survival rates in this young group of patients, while preserving white matter tracts and thus quality of life. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Predominant role of plasma membrane monoamine transporters in monoamine transport in 1321N1, a human astrocytoma-derived cell line.

    Science.gov (United States)

    Naganuma, Fumito; Yoshikawa, Takeo; Nakamura, Tadaho; Iida, Tomomitsu; Harada, Ryuichi; Mohsen, Attayeb S; Miura, Yamato; Yanai, Kazuhiko

    2014-05-01

    Monoamine neurotransmitters should be immediately removed from the synaptic cleft to avoid excessive neuronal activity. Recent studies have shown that astrocytes and neurons are involved in monoamine removal. However, the mechanism of monoamine transport by astrocytes is not entirely clear. We aimed to elucidate the transporters responsible for monoamine transport in 1321N1, a human astrocytoma-derived cell line. First, we confirmed that 1321N1 cells transported dopamine, serotonin, norepinephrine, and histamine in a time- and dose-dependent manner. Kinetics analysis suggested the involvement of low-affinity monoamine transporters, such as organic cation transporter (OCT) 2 and 3 and plasma membrane monoamine transporter (PMAT). Monoamine transport in 1321N1 cells was not Na(+) /Cl(-) dependent but was inhibited by decynium-22, an inhibitor of low-affinity monoamine transporters, which supported the importance of low-affinity transporters. RT-PCR assays revealed that 1321N1 cells expressed OCT3 and PMAT but no other neurotransmitter transporters. Another human astrocytoma-derived cell line, U251MG, and primary human astrocytes also exhibited the same gene expression pattern. Gene-knockdown assays revealed that 1321N1 and primary human astrocytes could transport monoamines predominantly through PMAT and partly through OCT3. These results might indicate that PMAT and OCT3 in human astrocytes are involved in monoamine clearance. © 2014 International Society for Neurochemistry.

  15. Anaplastic astrocytoma: prognostic factors and survival in 4807 patients with emphasis on receipt and impact of adjuvant therapy.

    Science.gov (United States)

    Shin, Jacob Y; Diaz, Aidnag Z

    2016-09-01

    To determine the receipt and impact of adjuvant therapy on overall survival (OS) for anaplastic astrocytoma (AA). Data were extracted from the National Cancer Data Base (NCDB). Chi square test, Kaplan-Meier method, and Cox regression models were employed in SPSS 22.0 (Armonk, NY: IBM Corp.) for data analyses. 4807 patients with AA diagnosed from 2004 to 2013 who underwent surgery were identified. 3243 (67.5 %) received adjuvant chemoRT, 525 (10.9 %) adjuvant radiotherapy (RT) alone, 176 (3.7 %) adjuvant chemotherapy alone and 863 (18.0 %) received no adjuvant therapy. Patients were more likely to receive adjuvant chemoRT if they were diagnosed in 2009-2013 (p = 0.022), were ≤ 50 years (p < 0.001), were male (p = 0.043), were Asian or White race (p < 0.001), had private insurance (p < 0.001), had income ≥$38,000 (p < 0.001), or underwent total resection (p < 0.003). Those who received adjuvant chemoRT had significantly better 5-year OS than the other adjuvant treatment types (41.8 % vs. 31.2 % vs. 29.8 % vs. 27.4 %, p < 0.001). This significant 5-year OS benefit was also observed regardless of age at diagnosis. Of those undergoing adjuvant chemoRT, those receiving ≥59.4 Gy had significantly better 5-year OS than those receiving <59.4 Gy (44.4 % vs. 25.9 %, p < 0.001). There was no significant difference in OS when comparing 59.4 Gy to higher RT doses. On multivariate analysis, receipt of adjuvant chemoRT, age at diagnosis, extent of disease, and insurance status were independent prognostic factors for OS. Adjuvant chemoRT is an independent prognostic factor for improved OS in AA and concomitant chemoRT should be considered for all clinically suitable patients who have undergone surgery for the disease.

  16. EFFECTS: an expanded access program of everolimus for patients with subependymal giant cell astrocytoma associated with tuberous sclerosis complex.

    Science.gov (United States)

    Fogarasi, Andras; De Waele, Liesbeth; Bartalini, Gabriella; Jozwiak, Sergiusz; Laforgia, Nicola; Verhelst, Helene; Petrak, Borivoj; Pedespan, Jean-Michel; Witt, Olaf; Castellana, Ramon; Crippa, Stefania; Gislimberti, Gabriella; Gyorsok, Zsuzsanna

    2016-08-08

    Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, has been shown to be effective and safe in the treatment of subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis complex (TSC). The Everolimus For Fast Expanded aCcess in TSC SEGA (EFFECTS) study was designed to provide everolimus access to patients with SEGA associated with TSC and to mainly assess the safety and also efficacy of everolimus in a real-world setting. EFFECTS was a phase 3b, open-label, noncomparative, multicenter, expanded access study. Eligible patients were ≥ 3 years of age, with a definite diagnosis of TSC, and with at least one SEGA lesion identified by MRI or CT scan. Patients received once daily everolimus (dose adjusted to attain a trough level of 5-15 ng/mL). Safety evaluation was the primary objective and included collection of adverse events (AEs) and serious AEs, with their severity and relationship to everolimus. Efficacy evaluation, which was the secondary objective, was based on the best overall response as per medical judgment. Of the 120 patients enrolled, 100 (83.3%) completed the study. Median age of patients was 11 years (range, 1-47). Median daily dose of everolimus was 5.82 mg (range, 2.0-11.8). Median duration of exposure was 56.5 weeks (range, 0.3-130). The overall incidence of AEs was 74.2%. Aphthous stomatitis (18 [15.0%]), pyrexia (18 [15.0%]), bronchitis (11 [9.2%]), and stomatitis (10 [8.3%]) were the most common AEs reported. Overall, 25 patients had grade 3 AEs; most frequent was stomatitis (4 [3.3%]). Grade 4 AEs were reported in three (2.5%) patients. A total of 62 (51.7%) patients had suspected drug-related AEs, of which 15 (12.5%) were of grade 3 or 4. In eight (6.7%) patients, AEs led to drug discontinuation. With regard to efficacy, 81 (67.5%) patients had a partial response, 35 (29.2%) had a stable disease, and one (0.8%) had progressive disease. The response was unknown in three (2.5%) patients. This study confirms the

  17. Caveolin-1 Regulates the P2Y2 Receptor Signaling in Human 1321N1 Astrocytoma Cells*

    Science.gov (United States)

    Ayala, Alondra M.; Martinez, Magdiel; Martinez-Rivera, Freddyson J.; Miranda, Jorge D.; Silva, Walter I.

    2016-01-01

    Damage to the CNS can cause a differential spatio-temporal release of multiple factors, such as nucleotides, ATP and UTP. The latter interact with neuronal and glial nucleotide receptors. The P2Y2 nucleotide receptor (P2Y2R) has gained prominence as a modulator of gliotic responses after CNS injury. Still, the molecular mechanisms underlying these responses in glia are not fully understood. Membrane-raft microdomains, such as caveolae, and their constituent caveolins, modulate receptor signaling in astrocytes; yet, their role in P2Y2R signaling has not been adequately explored. Hence, this study evaluated the role of caveolin-1 (Cav-1) in modulating P2Y2R subcellular distribution and signaling in human 1321N1 astrocytoma cells. Recombinant hP2Y2R expressed in 1321N1 cells and Cav-1 were found to co-fractionate in light-density membrane-raft fractions, co-localize via confocal microscopy, and co-immunoprecipitate. Raft localization was dependent on ATP stimulation and Cav-1 expression. This hP2Y2R/Cav-1 distribution and interaction was confirmed with various cell model systems differing in the expression of both P2Y2R and Cav-1, and shRNA knockdown of Cav-1 expression. Furthermore, shRNA knockdown of Cav-1 expression decreased nucleotide-induced increases in the intracellular Ca2+ concentration in 1321N1 and C6 glioma cells without altering TRAP-6 and carbachol Ca2+ responses. In addition, Cav-1 shRNA knockdown also decreased AKT phosphorylation and altered the kinetics of ERK1/2 activation in 1321N1 cells. Our findings strongly suggest that P2Y2R interaction with Cav-1 in membrane-raft caveolae of 1321N1 cells modulates receptor coupling to its downstream signaling machinery. Thus, P2Y2R/Cav-1 interactions represent a novel target for controlling P2Y2R function after CNS injury. PMID:27129210

  18. Childhood Astrocytomas Treatment

    Science.gov (United States)

    ... to grow. If fluid builds up around the brain and spinal cord, a cerebrospinal fluid diversion procedure may be done. Cerebrospinal fluid diversion is a method used to drain fluid that has built up around the brain ...

  19. Adjuvant temozolomide-based chemoradiotherapy versus radiotherapy alone in patients with WHO III astrocytoma. The Mainz experience

    Energy Technology Data Exchange (ETDEWEB)

    Mayer, Arnulf; Schwanbeck, Carina; Stockinger, Marcus; Vaupel, Peter; Schmidberger, Heinz [University Medical Center, Department of Radiooncology and Radiotherapy, Mainz (Germany); Sommer, Clemens [University Medical Center, Department of Neuropathology, Mainz (Germany); Giese, Alf; Renovanz, Mirjam [University Medical Center, Department of Neurosurgery, Mainz (Germany)

    2015-08-15

    It is currently unclear whether adjuvant therapy for WHO grade III anaplastic astrocytomas (AA) should be carried out as combined chemoradiotherapy with temozolomide (TMZ) - analogous to the approach for glioblastoma multiforme - or as radiotherapy (RT) alone. A retrospective analysis of data from 90 patients with AA, who were treated between November 1997 and February 2014. Assessment of overall (OS) and progression-free survival (PFS) was performed according to treatment categories: (1) 50 %, RT + TMZ according to protocol, (2) 11 %, RT + TMZ with dose reduction, (3) 26 %, RT alone, and (4) 13 %, individualized, primarily palliative therapy. No dose reduction was necessary in the RT alone group. Median OS was 85, 69, and 43 months for treatment categories 1/2, 3, and 4, respectively. These differences were not statistically significant. PFS was 35, 29, 48, and 33 months for categories 1, 2, 3, and 4, respectively; again without significant differences between categories. In a subgroup of 39 patients with known IDH1 R132H status, the presence of this mutation correlated with significantly longer OS (p = 0.01) and PFS (p = 0.002). Complete or partial tumor resection and younger age also correlated with a significantly better prognosis, and this influence persisted in multivariate analysis. In the IDH1 R132H subgroup analysis, only this marker retained an independent prognostic value. A general superiority of combined chemoradiotherapy compared to RT alone could not be demonstrated. Biomarkers for predicting the benefits of combination therapy using RT and TMZ are needed for patients with AA. (orig.) [German] Es ist derzeit unklar, ob bei anaplastischen Astrozytomen (AA) vom WHO-Grad III eine adjuvante Therapie analog zur Therapiestrategie beim Glioblastoma multiforme als kombinierte Radiochemotherapie mit Temozolomid (TMZ) oder als alleinige Radiotherapie (RT) durchgefuehrt werden sollte. Retrospektiv wurden die Daten von 90 Patienten mit AA, die zwischen November

  20. Exophytic pilocytic astrocytoma of the brain stem in an adult with encasement of the caudal cranial nerve complex (IX-XII): presurgical anatomical neuroimaging using MRI

    Energy Technology Data Exchange (ETDEWEB)

    Yousry, Indra; Yousry, Tarek A. [Department of Neuroradiology, Klinikum Grosshadern, Ludwig-Maximilians University, Marchioninistr. 15, 81377, Munich (Germany); Muacevic, Alexander; Olteanu-Nerbe, Vlad [Department of Neurosurgery, Klinikum Grosshadern, Ludwig-Maximilians University, Munich (Germany); Naidich, Thomas P. [Department of Radiology, Section of Neuroradiology, Mount Sinai Hospital, New York (United States)

    2004-07-01

    We describe a rare case of adult pilocytic astrocytoma in which exophytic growth from the brain stem presented as a right cerebellopontine angle mass. An initial MRI examination using T2- and T1-weighted images without and with contrast suggested the diagnosis of schwannoma. Subsequent use of 3D CISS (three-dimensional constructive interference in steady state) and T1-weighted contrast-enhanced 3D MP-RAGE (three-dimensional magnetization prepared rapid acquisition gradient echo) sequences led to the diagnosis of an exophytic brain stem tumor, documented the precise relationships of the tumor to cranial nerve VIII, revealed encasement of cranial nerves IX-XII (later confirmed intraoperatively), and provided the proper basis for planning surgical management. (orig.)

  1. Decreased Survival of Glioma Patients with Astrocytoma Grade IV (Glioblastoma Multiforme Associated with Long-Term Use of Mobile and Cordless Phones

    Directory of Open Access Journals (Sweden)

    Michael Carlberg

    2014-10-01

    Full Text Available On 31 May 2011 the WHO International Agency for Research on Cancer (IARC categorised radiofrequency electromagnetic fields (RF-EMFs from mobile phones, and from other devices that emit similar non-ionising electromagnetic fields, as a Group 2B, i.e., a “possible”, human carcinogen. A causal association would be strengthened if it could be shown that the use of wireless phones has an impact on the survival of glioma patients. We analysed survival of 1678 glioma patients in our 1997–2003 and 2007–2009 case-control studies. Use of wireless phones in the >20 years latency group (time since first use yielded an increased hazard ratio (HR = 1.7, 95% confidence interval (CI = 1.2–2.3 for glioma. For astrocytoma grade IV (glioblastoma multiforme; n = 926 mobile phone use yielded HR = 2.0, 95% CI = 1.4–2.9 and cordless phone use HR = 3.4, 95% CI = 1.04–11 in the same latency category. The hazard ratio for astrocytoma grade IV increased statistically significant per year of latency for wireless phones, HR = 1.020, 95% CI = 1.007–1.033, but not per 100 h cumulative use, HR = 1.002, 95% CI = 0.999–1.005. HR was not statistically significant increased for other types of glioma. Due to the relationship with survival the classification of IARC is strengthened and RF-EMF should be regarded as human carcinogen requiring urgent revision of current exposure guidelines.

  2. Radiotherapy in pediatric pilocytic astrocytomas. A subgroup analysis within the prospective multicenter study HIT-LGG 1996 by the German Society of Pediatric Oncology and Hematology (GPOH)

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, K. [Leipzig Univ. (Germany). Dept. of Radiotherapy and Radiation Oncology; Gnekow, A.; Falkenstein, F. [General Hospital of Augsburg (Germany). Hospital for Children and Adolescents] [and others

    2013-08-15

    Purpose: We evaluated clinical outcomes in the subset of patients who underwent radiotherapy (RT) due to progressive pilocytic astrocytoma within the Multicenter Treatment Study for Children and Adolescents with a Low Grade Glioma HIT-LGG 1996. Patients and methods: Eligibility criteria were fulfilled by 117 patients. Most tumors (65 %) were located in the supratentorial midline, followed by the posterior fossa (26.5 %) and the cerebral hemispheres (8.5 %). Median age at the start of RT was 9.2 years (range 0.7-17.4 years). In 75 cases, external fractionated radiotherapy (EFRT) was administered either as first-line nonsurgical treatment (n = 58) or after progression following primary chemotherapy (n = 17). The median normalized total dose was 54 Gy. Stereotactic brachytherapy (SBT) was used in 42 selected cases. Results: During a median follow-up period of 8.4 years, 4 patients (3.4 %) died and 33 (27.4 %) experienced disease progression. The 10-year overall (OS) and progression-free survival (PFS) rates were 97 and 70 %, respectively. No impact of the RT technique applied (EFRT versus SBT) on progression was observed. The 5-year PFS was 76 {+-} 5 % after EFRT and 65 {+-} 8 % after SBT. Disease progression after EFRT was not influenced by gender, neurofibromatosis type 1 (NF1) status, tumor location (hemispheres versus supratentorial midline versus posterior fossa), age or prior chemotherapy. Normalized total EFRT doses of more than 50.4 Gy did not improve PFS rates. Conclusion: EFRT plays an integral role in the treatment of pediatric pilocytic astrocytoma and is characterized by excellent tumor control. A reduction of the normalized total dose from 54 to 50.4 Gy appears to be feasible without jeopardizing tumor control. SBT is an effective treatment alternative. (orig.)

  3. Platform-Independent Genome-Wide Pattern of DNA Copy-Number Alterations Predicting Astrocytoma Survival and Response to Treatment Revealed by the GSVD Formulated as a Comparative Spectral Decomposition.

    Science.gov (United States)

    Aiello, Katherine A; Alter, Orly

    2016-01-01

    We use the generalized singular value decomposition (GSVD), formulated as a comparative spectral decomposition, to model patient-matched grades III and II, i.e., lower-grade astrocytoma (LGA) brain tumor and normal DNA copy-number profiles. A genome-wide tumor-exclusive pattern of DNA copy-number alterations (CNAs) is revealed, encompassed in that previously uncovered in glioblastoma (GBM), i.e., grade IV astrocytoma, where GBM-specific CNAs encode for enhanced opportunities for transformation and proliferation via growth and developmental signaling pathways in GBM relative to LGA. The GSVD separates the LGA pattern from other sources of biological and experimental variation, common to both, or exclusive to one of the tumor and normal datasets. We find, first, and computationally validate, that the LGA pattern is correlated with a patient's survival and response to treatment. Second, the GBM pattern identifies among the LGA patients a subtype, statistically indistinguishable from that among the GBM patients, where the CNA genotype is correlated with an approximately one-year survival phenotype. Third, cross-platform classification of the Affymetrix-measured LGA and GBM profiles by using the Agilent-derived GBM pattern shows that the GBM pattern is a platform-independent predictor of astrocytoma outcome. Statistically, the pattern is a better predictor (corresponding to greater median survival time difference, proportional hazard ratio, and concordance index) than the patient's age and the tumor's grade, which are the best indicators of astrocytoma currently in clinical use, and laboratory tests. The pattern is also statistically independent of these indicators, and, combined with either one, is an even better predictor of astrocytoma outcome. Recurring DNA CNAs have been observed in astrocytoma tumors' genomes for decades, however, copy-number subtypes that are predictive of patients' outcomes were not identified before. This is despite the growing number of

  4. Establishment and application of a novel patient-derived KIAA1549:BRAF-driven pediatric pilocytic astrocytoma model for preclinical drug testing.

    Science.gov (United States)

    Selt, Florian; Hohloch, Juliane; Hielscher, Thomas; Sahm, Felix; Capper, David; Korshunov, Andrey; Usta, Diren; Brabetz, Sebastian; Ridinger, Johannes; Ecker, Jonas; Oehme, Ina; Gronych, Jan; Marquardt, Viktoria; Pauck, David; Bächli, Heidi; Stiles, Charles D; von Deimling, Andreas; Remke, Marc; Schuhmann, Martin U; Pfister, Stefan M; Brummer, Tilman; Jones, David T W; Witt, Olaf; Milde, Till

    2017-02-14

    Pilocytic astrocytoma (PA) is the most frequent pediatric brain tumor. Activation of the MAPK pathway is well established as the oncogenic driver of the disease. It is most frequently caused by KIAA1549:BRAF fusions, and leads to oncogene induced senescence (OIS). OIS is thought to be a major reason for growth arrest of PA cells in vitro and in vivo, preventing establishment of PA cultures. Hence, valid preclinical models are currently very limited, but preclinical testing of new compounds is urgently needed. We transduced the PA short-term culture DKFZ-BT66 derived from the PA of a 2-year old patient with a doxycycline-inducible system coding for Simian Vacuolating Virus 40 Large T Antigen (SV40-TAg). SV40-TAg inhibits TP53/CDKN1A and CDKN2A/RB1, two pathways critical for OIS induction and maintenance. DNA methylation array and KIAA1549:BRAF fusion analysis confirmed pilocytic astrocytoma identity of DKFZ-BT66 cells after establishment. Readouts were analyzed in proliferating as well as senescent states, including cell counts, viability, cell cycle analysis, expression of SV40-Tag, CDKN2A (p16), CDKN1A (p21), and TP53 (p53) protein, and gene-expression profiling. Selected MAPK inhibitors (MAPKi) including clinically available MEK inhibitors (MEKi) were tested in vitro. Expression of SV40-TAg enabled the cells to bypass OIS and to resume proliferation with a mean doubling time of 45h allowing for propagation and long-term culture. Withdrawal of doxycycline led to an immediate decrease of SV40-TAg expression, appearance of senescent morphology, upregulation of CDKI proteins and a subsequent G1 growth arrest in line with the re-induction of senescence. DKFZ-BT66 cells still underwent replicative senescence that was overcome by TERT expression. Testing of a set of MAPKi revealed differential responses in DKFZ-BT66. MEKi efficiently inhibited MAPK signaling at clinically achievable concentrations, while BRAF V600E- and RAF Type II inhibitors showed paradoxical

  5. Radio-chemotherapy improves survival in IDH-mutant, 1p/19q non-codeleted secondary high-grade astrocytoma patients.

    Science.gov (United States)

    Juratli, Tareq A; Lautenschläger, Tim; Geiger, Kathrin D; Pinzer, Thomas; Krause, Mechthild; Schackert, Gabriele; Krex, Dietmar

    2015-09-01

    Isocitrate dehydrogenase (IDH) mutations are beginning to drive decisions on therapy for glioma patients. Here we sought to determine the impact of adjuvant treatment in patients with IDH-mutant, 1p/19q non-codeleted secondary high-grade astrocytoma (sHGA) WHO grades III/IV. Clinical data of 109 sHGA patients grades III/IV, in addition to IDH mutation-, 1p/19q-codeletion- and MGMT-promoter methylation status-were retrospectively analyzed. Survival analysis in relation to adjuvant treatment modalities and molecular profiling were performed. Out of 109 patients, 88 patients (80.7 %) harbored IDH mutations, 30 patients had a 1p/19q-codeletion (27.5 %) and 69 patients (63.3 %) exhibited a methylated MGMT-promoter status. At a median follow-up of 9.8 years, 62 patients (57 %) died. The postsurgical treatment included: radio-chemotherapy (RT-CT; 54.5 %), RT alone (19.3 %), and CT alone (22.7 %). The median overall survival (OS) in the entire group was 3.4 years (1.9-6.7 years). Patients who received RT-CT had a significantly longer OS compared with those who underwent RT alone (6.5 vs. 1.2 years, HR 0.35, CI 0.32-0.51, p = 0.011). In the IDH-mutant 1p/19q non-codeleted sHGA subgroup the RT-CT cohort had a significantly longer OS in comparison to the RT cohort (6.4 vs. 1.2 years, HR 2.7, CI 1.1-6.5, p = 0.022). In the stepwise multivariable Cox model for OS of all 88 IDH-mutant sHGA patients, survival was strongly associated with only one factor, namely, adjuvant RT-CT at diagnosis of a sHGA. This retrospective long-term study demonstrates that RT and CT (mostly PCV) significantly improves progression-free and overall survival in IDH-mutant secondary high-grade astrocytoma patients, regardless of 1p/19q-codeletion status.

  6. AUTOCOUNTER, an ImageJ JavaScript to analyze LC3B-GFP expression dynamics in autophagy-induced astrocytoma cells

    Directory of Open Access Journals (Sweden)

    L. Fassina

    2012-10-01

    Full Text Available An ImageJ JavaScript, AUTOCOUNTER, was specifically developed to monitor and measure LC3B-GFP expression in living human astrocytoma cells, namely T98G and U373-MG. Discrete intracellular GFP fluorescent spots derived from transduction of a Baculovirus replication-defective vector (BacMam LC3B-GFP, followed by microscope examinations at different times. After viral transgene expression, autophagy was induced by Rapamycin administration and assayed in ph-p70S6K/p70S6K and LC3B immunoblotting expression as well as by electron microscopy examinations. A mutated transgene, defective in LC3B lipidation, was employed as a negative control to further exclude fluorescent dots derived from protein intracellular aggregation. The ImageJ JavaScript was then employed to evaluate and score the dynamics changes of the number and area of LC3B-GFP puncta per cell in time course assays and in complex microscope examinations. In conclusion, AUTOCOUNTER enabled to quantify LC3B-GFP expression and to monitor dynamics changes in number and shapes of autophagosomal-like vesicles: it might therefore represent a suitable algorithmic tool for in vitro autophagy modulation studies.

  7. Anti-tumor immune response correlates with neurological symptoms in a dog with spontaneous astrocytoma treated by gene and vaccine therapy.

    Science.gov (United States)

    Pluhar, G Elizabeth; Grogan, Patrick T; Seiler, Charlie; Goulart, Michelle; Santacruz, Karen S; Carlson, Cathy; Chen, Wei; Olin, Mike R; Lowenstein, Pedro R; Castro, Maria G; Haines, Stephen J; Ohlfest, John R

    2010-04-26

    Gene therapy and vaccination have been tested in malignant glioma patients with modest, albeit encouraging results. The combination of these therapies has demonstrated synergistic efficacy in murine models but has not been reported in large animals. Gemistocytic astrocytoma (GemA) is a low-grade glioma that typically progresses to lethal malignancy despite conventional therapies. Until now there has been no useful animal model of GemA. Here we report the treatment of a dog with spontaneous GemA using the combination of surgery, intracavitary adenoviral interferon gamma (IFNgamma) gene transfer, and vaccination with glioma cell lysates mixed with CpG oligodeoxynucleotides. Surgical tumor debulking and delivery of Ad-IFNgamma into the resection cavity were performed. Autologous tumor cells grew slowly in culture, necessitating vaccination with allogeneic tumor lysate in four of the five vaccinations. Transient left-sided blindness and hemiparesis occurred following the fourth and fifth vaccinations. These neurological symptoms correlated with a peak in the levels of tumor-reactive IgG and CD8(+) T cells measured in the blood. All symptoms resolved and this dog remains tumor-free over 450 days following surgery. This case report preliminarily demonstrates the feasibility of treating dogs with spontaneous glioma using immune-based therapy and warrants further study using this therapeutic approach. Copyright 2010 Elsevier Ltd. All rights reserved.

  8. AUTOCOUNTER, an ImageJ JavaScript to analyze LC3B-GFP expression dynamics in autophagy-induced astrocytoma cells.

    Science.gov (United States)

    Fassina, L; Magenes, G; Inzaghi, A; Palumbo, S; Allavena, G; Miracco, C; Pirtoli, L; Biggiogera, M; Comincini, S

    2012-10-11

    An ImageJ JavaScript, AUTOCOUNTER, was specifically developed to monitor and measure LC3B-GFP expression in living human astrocytoma cells, namely T98G and U373-MG. Discrete intracellular GFP fluorescent spots derived from transduction of a Baculovirus replication-defective vector (BacMam LC3B-GFP), followed by microscope examinations at different times. After viral transgene expression, autophagy was induced by Rapamycin administration and assayed in ph-p70S6K/p70S6K and LC3B immunoblotting expression as well as by electron microscopy examinations. A mutated transgene, defective in LC3B lipidation, was employed as a negative control to further exclude fluorescent dots derived from protein intracellular aggregation. The ImageJ JavaScript was then employed to evaluate and score the dynamics changes of the number and area of LC3B-GFP puncta per cell in time course assays and in complex microscope examinations. In conclusion, AUTOCOUNTER enabled to quantify LC3B-GFP expression and to monitor dynamics changes in number and shapes of autophagosomal-like vesicles: it might therefore represent a suitable algorithmic tool for in vitro autophagy modulation studies.

  9. Spontaneous complete regression of hypothalamic pilocytic astrocytoma after partial resection in a child, complicated with Stevens-Johnson syndrome: a case report and literature review.

    Science.gov (United States)

    Samadian, Mohammad; Bakhtevari, Mehrdad Hosseinzadeh; Haddadian, Karim; Alavi, Hossein Afshin; Rezaei, Omidvar

    2016-04-01

    Pilocytic astrocytoma (PA) is the most common pediatric central nervous system glial neoplasm and the most common pediatric cerebellar tumor. The spontaneous regression that occurs after partial/subtotal resection is multifactorial, depending on multiple factors, as for the case of humoral and cell-mediated immune responses of the host to the implanted tumor. A 7-year-old boy was referred to a neurosurgery clinic with headache. Further imaging workup revealed hypothalamic PA. Partial resection of the lesions was performed with right-side pterional approach. The patient developed a severe panmucositis [Stevens-Johnson syndrome (SJS)] and respiratory failure plus conjunctivitis, due to phenytoin allergy. During the patient's 6-month follow-up, postoperative magnetic resonance imaging (MRI) revealed a residual tumor, and about 9 months later (at 15 months postoperatively), the MRI showed total regression of the tumor. Clinically, symptomatic PA may undergo spontaneous regression after partial resection. We report a well-documented case of spontaneous regression hypothalamic PA after partial resection that complicated with SJS. Immune system reaction in SJS may have a role in tumor behavior and spontaneous regression. Multiple studies confirmed spontaneous regression in PA after partial/subtotal resection. This phenomenon occurs due to humoral and cell-mediated host immune responses to the implanted tumor. The immune system reaction in SJS may have a role in tumor behavior and spontaneous regression.

  10. Noradrenaline increases intracellular glutathione in human astrocytoma U-251 MG cells by inducing glutamate-cysteine ligase protein via β3-adrenoceptor stimulation.

    Science.gov (United States)

    Yoshioka, Yasuhiro; Kadoi, Hisatsugu; Yamamuro, Akiko; Ishimaru, Yuki; Maeda, Sadaaki

    2016-02-05

    Glutathione (GSH) plays a critical role in protecting cells from oxidative damage. Since neurons rely on the supply of GSH from astrocytes to maintain optimal intracellular GSH concentrations, the GSH concentration of astrocytes is important for the survival of neighboring neurons against oxidative stress. The neurotransmitter noradrenaline is known to modulate the functions of astrocytes and has been suggested to have neuroprotective properties in neurodegenerative diseases. To elucidate the mechanisms underlying the neuroprotective properties of noradrenaline, in this study, we investigated the effect of noradrenaline on the concentrations of intracellular GSH in human U-251 malignant glioma (MG; astrocytoma) cells. Treatment of the cells with noradrenaline for 24h concentration-dependently increased their intracellular GSH concentration. This increase was inhibited by a non-selective β-adrenoceptor antagonist propranolol and by a selective β3-adrenoceptor antagonist SR59230A, but not by a non-selective α-adrenoceptor antagonist phenoxybenzamine, or by a selective β1-adrenoceptor antagonist atenolol or by a selective β2-adrenoceptor antagonist butoxamine. In addition, the selective β3-adrenoceptor agonist CL316243 increased the intracellular GSH in U-251 MG cells. Treatment of the cells with noradrenaline (10μM) for 24h increased the protein level of the catalytic subunit of glutamate-cysteine ligase (GCLc), the rate-limiting enzyme of GSH synthesis; and this increase was inhibited by SR59230A. These results thus suggest that noradrenaline increased the GSH concentration in astrocytes by inducing GCLc protein in them via β3-adrenoceptor stimulation. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. The differential diagnosis of pilocytic astrocytoma with atypical features and malignant glioma: an analysis of 16 cases with emphasis on distinguishing molecular features.

    Science.gov (United States)

    Cykowski, Matthew D; Allen, Richard A; Kanaly, Angela C; Fung, Kar-Ming; Marshall, Roxanne; Perry, Arie; Stolzenberg, Ethan D; Dunn, S Terence

    2013-12-01

    Rare pilocytic astrocytomas (PA) have atypical histologic and clinicoradiologic features that raise the differential diagnosis of glioblastoma. Whether ancillary studies can supplement histopathologic examination in placing these cases accurately on the spectrum of WHO Grade I PA to higher-grade glioma is not always clear, partly because these cases are not common. Here, ten PAs with atypical clinicoradiologic and histologic features and six pediatric glioblastoma multiforme (pGBMs) were analyzed for BRAF V600E, IDH1, IDH2, and TP53 mutations. Ki-67, p53, and p16 protein expression were also examined by immunohistochemistry. BRAF-KIAA1549 fusion status was assessed in the PA subgroup. The rate of BRAF-KIAA1549 fusion was high in these PAs (5/7 tumors) including four extracerebellar examples. A single BRAF V600E mutation was identified in the fusion-negative extracerebellar PA of a very young child who succumbed to the disease. TP53 mutations were present only in malignant gliomas, including three pGBMs and one case designated as PA with anaplastic features (with consultation opinion of pGBM). IDH1 and IDH2 were wild type in all cases, consistent with earlier findings that IDH mutations are not typical in high-grade gliomas of patients ≤14 years of age. Immunohistochemical studies showed substantial overlap in Ki-67 labeling indices, an imperfect correlation between p53 labeling and TP53 mutation status, and complete p16 loss in only two pGBMs but in no PAs. These results suggest that (a) BRAF-KIAA1549 fusion may be common in PAs with atypical clinicoradiologic and histologic features, including those at extracerebellar sites, (b) BRAF V600E mutation is uncommon in extracerebellar PAs, and (c) TP53 mutation analysis remains a valuable tool in identifying childhood gliomas that will likely behave in a malignant fashion.

  12. Phase III randomized study of radiation and temozolomide versus radiation and nitrosourea therapy for anaplastic astrocytoma: results of NRG Oncology RTOG 9813.

    Science.gov (United States)

    Chang, Susan; Zhang, Peixin; Cairncross, J Gregory; Gilbert, Mark R; Bahary, Jean-Paul; Dolinskas, Carol A; Chakravarti, Arnab; Aldape, Kenneth D; Bell, Erica H; Schiff, David; Jaeckle, Kurt; Brown, Paul D; Barger, Geoffrey R; Werner-Wasik, Maria; Shih, Helen; Brachman, David; Penas-Prado, Marta; Robins, H Ian; Belanger, Karl; Schultz, Christopher; Hunter, Grant; Mehta, Minesh

    2017-02-01

    The primary objective of this study was to compare the overall survival (OS) of patients with anaplastic astrocytoma (AA) treated with radiotherapy (RT) and either temozolomide (TMZ) or a nitrosourea (NU). Secondary endpoints were time to tumor progression (TTP), toxicity, and the effect of IDH1 mutation status on clinical outcome. Eligible patients with centrally reviewed, histologically confirmed, newly diagnosed AA were randomized to receive either RT+TMZ (n = 97) or RT+NU (n = 99). The study closed early because the target accrual rate was not met. Median follow-up time for patients still alive was 10.1 years (1.9-12.6 y); 66% of the patients died. Median survival time was 3.9 years in the RT/TMZ arm (95% CI, 3.0-7.0) and 3.8 years in the RT/NU arm (95% CI, 2.2-7.0), corresponding to a hazard ratio (HR) of 0.94 (P = .36; 95% CI, 0.67-1.32). The differences in progression-free survival (PFS) and TTP between the 2 arms were not statistically significant. Patients in the RT+NU arm experienced more grade ≥3 toxicity (75.8% vs 47.9%, P < .001), mainly related to myelosuppression. Of the 196 patients, 111 were tested for IDH1-R132H status (60 RT+TMZ and 51 RT+NU). Fifty-four patients were IDH negative and 49 were IDH positive with a better OS in IDH-positive patients (median survival time 7.9 vs 2.8 y; P = .004, HR = 0.50; 95% CI, 0.31-0.81). RT+TMZ did not appear to significantly improve OS or TTP for AA compared with RT+ NU. RT+TMZ was better tolerated. IDH1-R132H mutation was associated with longer survival.

  13. Low rates of recurrence and slow progression of pediatric pilocytic astrocytoma after gross-total resection: justification for reducing surveillance imaging.

    Science.gov (United States)

    Dodgshun, Andrew J; Maixner, Wirginia J; Hansford, Jordan R; Sullivan, Michael J

    2016-05-01

    OBJECTIVE Pilocytic astrocytomas (PAs) are common brain tumors in children. Optimal management of PA is gross-total resection (GTR), after which event-free survival (EFS) is excellent. The tempo of recurrences, when they do occur, is relatively sparsely reported, and there is no agreed upon surveillance recommendation for patients in this category. It has been suggested that surveillance MRI is performed too frequently and could be safely reduced in both frequency and duration. The authors conducted a retrospective review of pediatric patients with PA who underwent GTR at a single institution over an 18-year period and who had documented recurrences. METHODS All patients under 18 years of age who had undergone GTR of a PA between 1996 and 2013 were included in the study. Clinical, radiological, and tumor characteristics were recorded. RESULTS Sixty-seven patients met the criteria for GTR over the period studied. The 5-year EFS rate was 95% (95% CI 89%-100%) and overall survival was 100%. Recurrences showed a nonsignificant trend of occurring more commonly in patients with persistent nonenhancing FLAIR abnormalities after surgery, but there was no difference with regard to tumor location. All recurrences occurred before 3 years postresection, all were asymptomatic, and all patients were observed for at least one additional scan after the initial detection during routine surveillance MRI before further therapy was undertaken. CONCLUSIONS EFS and overall survival are excellent after GTR in this population with PAs. Progression after recurrence occurs slowly and is asymptomatic. A less intensive schedule of MRI surveillance in this group of patients would result in time and cost savings, without compromising safety. The authors suggest a schedule of 6 MRI scans to be obtained postoperatively, at 3-6 months, then at 1, 2, 3.5, and 5 years.

  14. Using urinary bFGF and TIMP3 levels to predict the presence of juvenile pilocytic astrocytoma and establish a distinct biomarker signature.

    Science.gov (United States)

    Pricola Fehnel, Katie; Duggins-Warf, Micah; Zurakowski, David; McKee-Proctor, Maxwell; Majumder, Rajarshi; Raber, Michael; Han, Xuezhe; Smith, Edward R

    2016-10-01

    OBJECTIVE The authors report the use of urinary biomarkers as a novel, noninvasive technique to detect juvenile pilocytic astrocytomas (JPAs), capable of distinguishing JPAs from other CNS diseases, including other brain tumors. Preliminary screening of an array of tumors implicated proteases (including matrix metalloproteinases [MMPs]) and their inhibitors (tissue inhibitors of metalloproteinase [TIMPs]) as well as growth factors (including basic fibroblast growth factor [bFGF]) as candidate biomarkers. These data led the authors to hypothesize that tissue inhibitor of metalloproteinase 3 (TIMP3) and bFGF would represent high-probability candidates as JPA-specific biomarkers. METHODS Urine was collected from 107 patients, which included children with JPA (n = 21), medulloblastoma (n = 17), glioblastoma (n = 9), arteriovenous malformations (n = 25), moyamoya (n = 14), and age- and sex-matched controls (n = 21). Biomarker levels were quantified with enzyme-linked immunosorbent assay, tumor tissue expression was confirmed with immunohistochemical analysis, and longitudinal biomarker expression was correlated with imaging. Results were subjected to univariate and multivariate statistical analyses. RESULTS Using optimal urinary cutoff values of bFGF > 1.0 pg/μg and TIMP3 > 3.5 pg/μg, multiplexing bFGF and TIMP3 predicts JPA presence with 98% accuracy. Multiplexing bFGF and MMP13 distinguishes JPA from other brain tumor subtypes with up to 98% accuracy. Urinary biomarker expression correlated with both tumor immunohistochemistry and in vitro tumor levels. Urinary bFGF and TIMP3 decrease following successful tumor treatment and correlate with changes in tumor size. CONCLUSIONS This study identifies 2 urinary biomarkers-bFGF and TIMP3-that successfully detect one of the most common pediatric brain tumors with high accuracy. These data highlight potential benefits of urinary biomarkers and support their utility as diagnostic tools in the treatment of children with JPA.

  15. Ketamine suppresses the substance P-induced production of IL-6 and IL-8 by human U373MG glioblastoma/astrocytoma cells.

    Science.gov (United States)

    Yamaguchi, Keisuke; Kumakura, Seiichiro; Murakami, Taisuke; Someya, Akimasa; Inada, Eiichi; Nagaoka, Isao

    2017-03-01

    The neuropeptide substance P (SP) is an important mediator of neurogenic inflammation within the central and peripheral nervous systems. SP has been shown to induce the expression of pro-inflammatory cytokines implicated in the pathogenesis of several disorders of the human brain via the neurokinin-1 receptor (NK-1R). Ketamine, an intravenous anesthetic agent, functions as a competitive antagonist of the excitatory neurotransmission N-methyl-D‑aspartate (NMDA) receptor, and also antagonizes the NK-1R by interfering with the binding of SP. In the present study, we investigated the anti-inflammatory effects of ketamine on the SP-induced activation of a human astrocytoma cell line, U373MG, which expresses high levels of NK-1R. The results from our experiments indicated that ketamine suppressed the production of interleukin (IL)-6 and IL-8 by the U373MG cells. Furthermore, ketamine inhibited the SP-induced activation of extracellular signal‑regulated kinase (ERK)1/2, p38 mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB). Taken together, these observations suggest that ketamine may suppress the SP-induced activation (IL-6 and IL-8 production) of U373MG cells by inhibiting the phosphorylation of signaling molecules (namely ERK1/2, p38 MAPK and NF-κB), thereby exerting anti‑inflammatory effects. Thus, ketamine may modulate SP-induced inflammatory responses by NK-1R‑expressing cells through the suppression of signaling molecules (such as ERK1/2, p38 MAPK and NF-κB).

  16. SU-E-J-212: MR Diffusion Tensor Imaging for Assessment of Tumor and Normal Brain Tissue Responses of Juvenile Pilocytic Astrocytoma Treated by Proton Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Hou, P; Park, P; Li, H; Zhu, X; Mahajan, A; Grosshans, D [M.D. Anderson Cancer Center, Houston, TX (United States)

    2015-06-15

    Purpose: Diffusion tensor imaging (DTI) can measure molecular mobility at the cellular level, quantified by the apparent diffusion coefficient (ADC). DTI may also reveal axonal fiber directional information in the white matter, quantified by the fractional anisotropy (FA). Juvenile pilocytic astrocytoma (JPA) is a rare brain tumor that occurs in children and young adults. Proton therapy (PT) is increasingly used in the treatment of pediatric brain tumors including JPA. However, the response of both tumors and normal tissues to PT is currently under investigation. We report tumor and normal brain tissue responses for a pediatric case of JPA treated with PT assessed using DTI. Methods: A ten year old male with JPA of the left thalamus received passive scattered PT to a dose of 50.4 Gy (RBE) in 28 fractions. Post PT, the patient has been followed up in seven years. At each follow up, MRI imaging including DTI was performed to assess response. MR images were registered to the treatment planning CT and the GTV mapped onto each MRI. The GTV contour was then mirrored to the right side of brain through the patient’s middle line to represent normal brain tissue. ADC and FA were measured within the ROIs. Results: Proton therapy can completely spare contra lateral brain while the target volume received full prescribed dose. From a series of MRI ADC images before and after PT at different follow ups, the enhancement corresponding to GTV had nearly disappeared more than 2 years after PT. Both ADC and FA demonstrate that contralateral normal brain tissue were not affect by PT and the tumor volume reverted to normal ADC and FA values. Conclusion: DTI allowed quantitative evaluation of tumor and normal brain tissue responses to PT. Further study in a larger cohort is warranted.

  17. The inhibitory effect of CIL-102 on the growth of human astrocytoma cells is mediated by the generation of reactive oxygen species and induction of ERK1/2 MAPK

    Energy Technology Data Exchange (ETDEWEB)

    Teng, Chih-Chuan [Institute of Nursing and Department of Nursing, Chang Gung University of Science and Technology, Chronic Diseases and Health Promotion Research Center, CGUST, Taiwan (China); Institute of Basic Medicine Science, National Cheng Kung University, Tainan, Taiwan (China); Kuo, Hsing-Chun [Institute of Nursing and Department of Nursing, Chang Gung University of Science and Technology, Chronic Diseases and Health Promotion Research Center, CGUST, Taiwan (China); Cheng, Ho-Chen [Department of General Education, Chang Gung University of Science and Technology, CGUST, Taiwan (China); Wang, Ting-Chung [Department of Neurosurgery, Chang Gung Memorial Hospital, Chia-Yi Center, Chiayi, Taiwan (China); Graduate Institute of Clinical Medical Sciences, Chang Gung University, Gueishan, Taiwan (China); Sze, Chun-I, E-mail: szec@mail.ncku.edu.tw [Institute of Basic Medicine Science, Department of Cell Biology and Anatomy and Pathology, National Cheng Kung University, Tainan, Taiwan (China)

    2012-08-15

    CIL-102 (1-[4-(furo[2,3-b]quinolin-4-ylamino)phenyl]ethanone) is the major active agent of the alkaloid derivative of Camptotheca acuminata, with multiple pharmacological activities, including anticancer effects and promotion of apoptosis. The mechanism by which CIL-102 inhibits growth remains poorly understood in human astrocytoma cells. Herein, we investigated the molecular mechanisms by which CIL-102 affects the generation of reactive oxygen species (ROS) and cell cycle G2/M arrest in glioma cells. Treatment of U87 cells with 1.0 μM CIL-102 resulted in phosphorylation of extracellular signal-related kinase (ERK1/2), downregulation of cell cycle-related proteins (cyclin A, cyclin B, cyclin D1, and cdk1), and phosphorylation of cdk1Tyr{sup 15} and Cdc25cSer{sup 216}. Furthermore, treatment with the ERK1/2 inhibitor PD98059 abolished CIL-102-induced Cdc25cSer{sup 216} expression and reversed CIL-102-inhibited cdk1 activation. In addition, N-acetyl cysteine (NAC), an ROS scavenger, blocked cell cycle G2/M arrest and phosphorylation of ERK1/2 and Cdc25cSer{sup 216} in U87 cells. CIL-102-mediated ERK1/2 and ROS production, and cell cycle arrest were blocked by treatment with specific inhibitors. In conclusion, we have identified a novel CIL-102-inhibited proliferation in U87 cells by activating the ERK1/2 and Cdc25cSer{sup 216} cell cycle-related proteins and inducing ROS production; this might be a new mechanism in human astrocytoma cells. -- Highlights: ► We show the effects of CIL-102 on the G2/M arrest of human astrocytoma cells. ► ROS and the Ras/ERK1/2 triggering pathways are involved in the CIL-102 treatment. ► CIL-102 induces sustained activation of ERK1/2 and Cdc25c and ROS are required.

  18. {sup 18}F-FDG PET/CT-Negative Recurrent High-Grade Anaplastic Astrocytoma Detected by {sup 18}F-FDOPA PET-CT

    Energy Technology Data Exchange (ETDEWEB)

    Karunanithi, Sellam; Singh, Harmandeep; Sharma, Punit; Gupta, Deepak Kumar; Bal, Chandrasekhar [All India Institute of Medical Sciences, New Delhi (India)

    2013-12-15

    A 37-year-old woman with grade 3 anaplastic astrocytoma (AA) of the left frontal lobe, underwent surgical excision, chemotherapy and external beam radiation therapy in 2004. After being in remission for 5 years, recurrence was suspected clinically when she presented with seizures. The result of contrast-enhanced magnetic resonance imaging (MRI) was equivocal for recurrence and radiation necrosis (not available ). The patient was then referred for {sup 18}F-fluorodeoxyglucose ({sup 18}F-FDG) positron emission tomography-computed tomography (PET-CT), as the initial primary tumour was high grade in nature. {sup 18}F-FDG PET-CT was negative for recurrence and demonstrated only post-operative changes in the left frontal region (Fig. 1a, b, arrow). Due to strong clinical suspicion, 3,4-dihydroxy-6-{sup 18}F-fluoro-L-phenylalanine ({sup 18}F-FDOPA) PET-CT was done, 5 days after {sup 18}F-FDG PET-CT. The study revealed an {sup 18}F-FDOPA-avid mass lesion in the left frontal region (Fig. 1c, d, arrow), thereby confirming the presence of recurrent disease. The patient underwent surgical resection of the mass, and it was confirmed by histopathology as grade 3 AA. However, after a short asymptomatic period of 4 months the patient became symptomatic again. Follow-up MRI after 6 months of surgery revealed presence of ipsilateral and contralateral multifocal contrast enhancing recurrent mass lesions (Fig. 1e, f, arrow), suggesting the progression of disease. The patient was started on temozolamide but she died after 8 months' follow-up. Though MRI is routinely used in assessment of brain tumours, its ability to differentiate between treatment-induced changes and residual or recurrent tumour is limited. {sup 18}F-FDG PET was the first tracer used for assessment of brain tumours; however, it has a low tumour-to-background ratio in brain, limiting its utility. {sup 18}F-FDG uptake correlates with tumour grade, with high-grade gliomas (grades III and IV) showing higher uptake

  19. Everolimus for subependymal giant cell astrocytoma in patients with tuberous sclerosis complex: 2-year open-label extension of the randomised EXIST-1 study.

    Science.gov (United States)

    Franz, David Neal; Belousova, Elena; Sparagana, Steven; Bebin, E Martina; Frost, Michael; Kuperman, Rachel; Witt, Olaf; Kohrman, Michael H; Flamini, J Robert; Wu, Joyce Y; Curatolo, Paolo; de Vries, Petrus J; Berkowitz, Noah; Anak, Oezlem; Niolat, Julie; Jozwiak, Sergiusz

    2014-12-01

    In the EXIST-1 trial, initiated on Aug 10, 2009, more than 35% of patients with subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis complex had at least 50% reduction in SEGA volume after 9·6 months of treatment with everolimus. In this Article, we report interim data (up to Jan 11, 2013) to support longer-term tolerability and efficacy of everolimus from the continuing 4-year extension phase of EXIST-1. We assessed data from a prospective, open-label extension of a multicentre, phase 3, randomised, double-blind, placebo-controlled study in patients with tuberous sclerosis complex who had SEGA that was growing and needed treatment. In this extension study, we included all patients who had been assigned everolimus during the double-blind, randomised phase of the trial and those patients who crossed over from the placebo group to receive everolimus during the randomised phase or at the start of the extension phase. All patients received oral everolimus at a starting dose of 4·5 mg/m(2) per day. Everolimus dose was subsequently adjusted subject to tolerability to attain blood trough concentrations of 5-15 ng/mL. An independent central radiology review team assessed SEGA response (at least a 50% reduction from baseline in total volume of all target SEGAs; the primary endpoint) by MRI at 12, 24, and 48 weeks, then every year thereafter in all patients who received at least one dose of everolimus. This study was registered with ClinicalTrials.gov, number NCT00789828. Of the original 117 randomly assigned patients, 111 were given everolimus between Aug 20, 2009, and Jan 11, 2013 (date of data cutoff); we included these patients in our longer-term analysis. Median duration of everolimus exposure was 29·3 months (IQR 19·4-33·8). Median follow-up was 28·3 months (IQR 19·3-33·0). 54 (49%) patients had a response of 50% or greater reduction in SEGA volume (95% CI 39·0-58·3), and duration of response was between 2·1 and 31·1 months (median

  20. Using co-registration of single photon emission computed tomography and magnetic resonance imaging to place an intracranial grid for electrode monitoring, leading to resection of a frontal lobe astrocytoma

    Energy Technology Data Exchange (ETDEWEB)

    Hughes, T.; Barnden, L.; Rowe, C.C. [the Queen Elizabeth Hospital , Adelaide, SA (Australia). Department of Nuclear Medicine

    1998-06-01

    Full text: A 24 year old female had previously been treated with radiotherapy for a low-grade astrocytoma of the left frontal lobe. Despite medication, she had since suffered increasingly frequent partial seizures which dramatically reduced her quality of life. She was assessed for resection of the epileptic focus. Inter-ictal and ictal single photon emission computed tomography (SPECT) were acquired following injections of {sup 99m}Tc HMPAO (CERETEC). Routine image interpretation did not allow confident localization of the seizure focus. However, when these images were superimposed and subtracted, an area of ictal hyperperfusion on the posterior margin of the tumour was identified. The resultant image was co-registered with magnetic resonance imaging (MRI). A subdural electrode grid was implanted over this area and adjacent frontal cortex. Subsequent ictal electroencephalogram (EEG) recordings confirmed that this area was the seizure focus. Local cortical stimulation through the grid indicated that it could be safely resected. Following left frontal lobectomy using margins defined by the subdural grid, the patient has been seizure free and suffered no neurological deficits. This case study is an example of the benefits to be gained by the co-registration of functional and anatomical imaging

  1. Leptomeningeal dissemination of pilocytic astrocytoma at diagnosis in childhood: two cases report Disseminação leptomeníngea de astrocitoma pilocítico ao diagnóstico: relato de dois casos

    Directory of Open Access Journals (Sweden)

    Eberval Gadelha Figueiredo

    2003-09-01

    Full Text Available Pilocytic astrocytoma (PA is a benign tumor that rarely spread along the neuraxis. At the moment there are no more than five cases of leptomeningeal dissemination (LD from PA at diagnosis described in the literature. Different patterns of presentation or recurrence may be noted: local recurrence, malignant transformation, multicentric disease or metastatic disease. LD and multicentric disease can be distinct pathological entities. We report two cases and analyse literature, emphasizing leptomeningeal spread at presentation. Hydrocephalus, biopsy and parcial ressection are likely to be favorable factors to the occurrence of LD. Otherwise, LD may be part of natural history of PA, as evidenced by its ocurrence in non-treated cases.Astrocitoma pilocítico (AP é tumor benigno que raramente se dissemina ao longo do neuroeixo. Até o momento não há mais que cinco casos de AP que se tenham apresentado com disseminação leptomeníngea (DL descritos na literatura. Diferentes padrões de apresentação ou recorrência podem ser observados: recorrência local, transformação maligna, doença multicêntrica ou doença metastática. DL e doença multicêntrica podem ser entidades diferentes. Relatamos dois casos e analisamos a literatura. Hidrocefalia, biópsia e ressecção parcial são provavelmente fatores predisponentes à DL. Por outro lado, DL pode ser parte da história natural de AP, como pode ser evidenciado pela sua ocorrência em casos não tratados.

  2. The role of temozolomide in the management of patients with newly diagnosed anaplastic astrocytoma: a comparison of survival in the era prior to and following the availability of temozolomide.

    Science.gov (United States)

    Strowd, Roy E; Abuali, Inas; Ye, Xiaobu; Lu, Yao; Grossman, Stuart A

    2016-03-01

    Adding temozolomide (TMZ) to radiation for patients with newly-diagnosed anaplastic astrocytomas (AAs) is common clinical practice despite the lack of prospective studies demonstrating a survival advantage. Two retrospective studies, each with methodologic limitations, provide conflicting advice regarding treatment. This single-institution retrospective study was conducted to determine survival trends in patients with AA. All patients ≥18 years with newly-diagnosed AA treated at Johns Hopkins from 1995 to 2012 were included. As we incorporated TMZ into high-grade glioma treatment regimens in 2004, patients were divided into pre-2004 and post-2004 groups for analysis. Clinical, radiographic, and pathologic data were collected. Median overall survival (OS) was calculated using Kaplan-Meier estimates. A total of 196 patients were identified; 74 pre-2004 and 122 post-2004; mean age 47 ± 15 years; 57 % male; 87 % white, 69 % surgical debulking. Mean RT dose 5676 + 746 cGy; duration of concurrent chemoradiation 5.8 ± 0.8 weeks; and mean adjuvant chemotherapy 4.3 + 2.8 cycles. Baseline prognostic factors did not differ between groups. Chemotherapy was administered to 12 % of patients pre-2004 (TMZ = 1, procarbazine, lomustine and vincristine = 2, carmustine wafer = 6) and 94 % post-2004 (TMZ in all, p < 0.001). Median OS was 32 months (95 % CI 23-43). Survival was longer in the post-2004 cohort (37 mo, 24-64) than pre-2004 (27 mo, 19-40; HR 0.75, 0.53-1.06, p = 0.11). Multivariate analysis controlling for age, Karnofsky performance status, and extent of resection revealed a 36 % reduced risk of death (HR 0.64, 0.44-0.91, p = 0.015) in patients treated post-2004. This retrospective review found survival in newly diagnosed patients with AA improved with the addition of temozolomide to standard radiation. Until prospective randomized phase III data are available, these data support the practice of incorporating TMZ in the management of

  3. The effect of everolimus on renal angiomyolipoma in patients with tuberous sclerosis complex being treated for subependymal giant cell astrocytoma: subgroup results from the randomized, placebo-controlled, Phase 3 trial EXIST-1

    Science.gov (United States)

    Kingswood, J. Chris; Jozwiak, Sergiusz; Belousova, Elena D.; Frost, Michael D.; Kuperman, Rachel A.; Bebin, E. Martina; Korf, Bruce R.; Flamini, J. Robert; Kohrman, Michael H.; Sparagana, Steven P.; Wu, Joyce Y.; Brechenmacher, Thomas; Stein, Karen; Berkowitz, Noah; Bissler, John J.; Franz, David N.

    2014-01-01

    Background Tuberous sclerosis complex (TSC) is characterized by benign tumours in multiple organs, including the brain, kidneys, skin, lungs and heart. Our objective was to evaluate everolimus, an mTOR inhibitor, in the treatment of angiomyolipoma in patients with subependymal giant cell astrocytoma (SEGA) associated with TSC. Methods EXamining everolimus In a Study of Tuberous Sclerosis Complex-1 (NCT00789828), a prospective, double-blind, randomized, placebo-controlled, Phase 3 study, examined everolimus in treating SEGA associated with TSC. Patients with serial SEGA growth from pre-baseline to baseline scans were randomly assigned (2:1) to receive 4.5 mg/m2/day everolimus (target blood trough: 5–15 ng/mL; n = 78) or placebo (n = 39). Angiomyolipoma response rates were analysed in patients (n = 44) with target baseline angiomyolipoma lesions (≥1 angiomyolipoma; longest diameter ≥1.0 cm). An angiomyolipoma response rate, defined as the proportion of patients with confirmed angiomyolipoma response, was assessed by kidney CT or MRI screening at baseline, at 12, 24 and 48 weeks and annually. Results Angiomyolipoma response rates were 53.3% (16/30) and 0% (0/14) for everolimus- and placebo-treated patients, respectively. Angiomyolipoma reductions ≥50% in the sum of volumes of all target lesions were seen only in everolimus-treated patients (56.5, 78.3 and 80.0%) compared with placebo-treated patients (0% at each time point) at Weeks 12, 24 and 48, respectively. Greater percentages of everolimus-treated patients had angiomyolipoma reductions ≥30% at these same time points (82.6, 100 and 100% versus 8.3, 18.2 and 16.7% for everolimus versus placebo, respectively). Conclusions Everolimus showed efficacy in reducing angiomyolipoma lesion volume in patients with SEGA associated with TSC. The trial is registered with ClinicalTrials.gov, number NCT00789828; http://clinicaltrials.gov/ct2/show/NCT00789828?term=EXIST-1&rank=1. PMID:24729041

  4. Índice de astrócitos gemistocíticos e imuno-expressão da proteína p53 em astrocitomas, grau II e III OMS Fraction of gemistocytic astrocytes and immunoexpression of p53 protein in astrocytomas grade II and III (WHO

    Directory of Open Access Journals (Sweden)

    Dely Cristina Martins

    2001-12-01

    Full Text Available Foram estudados, retrospectivamente, 22 pacientes com diagnóstico de astrocitomas grau II (n=17 e III (n=5, OMS, no período de 1990 a 1998, cujos laudos histopatológicos descreviam a presença gemistocitos com o objetivo de determinar o índice de astrócitos gemistocíticos, investigar a imuno-expressão da proteína p53 e confrontá-los com o intervalo até a recorrência da neoplasia. O índice de astrócitos gemistocíticos, em cada caso, foi calculado a partir da razão entre o número de gemistocitos e o número total de células neoplásicas contadas, no mínimo 1000. Imuno-expressão nuclear da proteína p53 foi avaliada em astrócitos e gemistocitos neoplásicos; tanto a freqüência (7/22, como o índice de imuno-expressão positiva da p53 em gemistocitos, independentemente do grau histológico da neoplasia, foram inferiores aos relatados na literatura. Não se observou correlação entre o índice de astrócitos gemistocíticos e a imuno-expressão positiva da p53.Twenty-two patients with astrocytomas, grade II or III WHO, were studied from 1990 to 1998. In all cases, histopathology showed that the astrocytomas had a gemistocytic component. The aims of this study were to establish the fraction of gemistocytic astrocytes, to investigate p53 protein immunoexpression and to evaluate correlations between these two parameters with the tumour outcome. Tumor cells were quantified at high-power magnification (x400. At least 1000 neoplastic cells (small neoplastic astrocytes plus gemistocytes were counted in each specimen. The percentage of gemistocytes was defined as the gemistocytic index. Nuclear expression of p53 protein was evaluated in neoplastic astrocytes and gemistocytes. Both the frequency (7/22 as well the p53 immunoexpression indices in gemistocytes, regardless of the grade of the astrocytomas, were inferior from those reported in the literature. No correlation was found between the gemistocytic indices and the p53

  5. Low-grade astrocytoma: surgical outcomes in eloquent versus non-eloquent brain areas Astrocitoma de baixo grau: resultado cirúrgico em área eloquente versus não eloquente

    Directory of Open Access Journals (Sweden)

    André de Macedo Bianco

    2012-01-01

    Full Text Available A retrospective study of 81 patients with low-grade astrocytoma (LGA comparing the efficacy of aggressive versus less aggressive surgery in eloquent and non-eloquent brain areas was conducted. Extent of surgical resection was analyzed to assess overall survival (OS and progression- free survival (PFS. Degree of tumor resection was classified as gross total resection (GTR, subtotal resection (STR or biopsy. GTR, STR and biopsy in patients with tumors in non-eloquent areas were performed in 31, 48 and 21% subjects, whereas in patients with tumors in eloquent areas resections were 22.5, 35 and 42.5%. Overall survival was 4.7 and 1.9 years in patients with tumors in non-eloquent brain areas submitted to GTR/STR and biopsy (p=0.013, whereas overall survival among patients with tumors in eloquent area was 4.5 and 2.1 years (p=0.33. Improved outcome for adult patients with LGA is predicted by more aggressive surgery in both eloquent and non-eloquent brain areas.Foi realizado estudo retrospectivo em 81 pacientes com astrocitoma de baixo grau (LGA comparando a eficácia da ressecção cirúrgica com cirurgia menos agressiva em relação à área eloquente e não eloquente do cérebro. A extensão da ressecção cirúrgica foi analisada para avaliar a sobrevida geral (OS e o tempo livre de doença (PFS. O grau da ressecção cirúrgica foi classificado como ressecção total (GTR, subtotal (STR e biópsia. Nos pacientes com lesão em área não eloquente foram realizadas GTR, STR e biópsia em 31, 48 e 21% dos casos, enquanto, naqueles com lesão em área eloquente, em 22,5, 35 e 42,5%, respectivamente. A sobrevida geral foi de 4,7 e 1,9 anos em pacientes com lesões em área não eloquente submetidos à GTR/STR e biópsia (p=0,013. Nos pacientes com lesão em áreas eloquentes, a sobrevida geral foi de 4,5 e 2,1 anos (p=0,33, respectivamente. A extensão da ressecção é fator preditivo de sobrevida tanto nas lesões em áreas eloquentes quanto nas n

  6. Complejo nódulo subependimario-astrocitoma subependimario gigantocelular en niños con esclerosis tuberosa Subependymal nodules-subependymal giant cell astrocytoma complex in children with tuberous sclerosis

    Directory of Open Access Journals (Sweden)

    Lucas Bongiorni

    2009-01-01

    Full Text Available El objetivo fue describir las características clínico imagenológicas de niños con esclerosis tuberosa que presentaron el complejo Nódulo Subependimario (NS-Astrocitoma Subependimario Gigantocelular(ASGC y analizar el comportamiento evolutivo de dicho "complejo" para detectar precozmente su crecimiento y evitar las complicaciones de la hipertensión endocraneana (HTE. Evaluamos 22 pacientes con diagnóstico anátomo patológico de ASGC. El diagnóstico del tumor se realizó a una media de 10.1 años. Pudimos observar la evolución de NS a ASGC; estos NS se ubicaron adyacentes al agujero de Monro y con el tiempo tuvieron un importante crecimiento con intensa captación de contraste e hidrocefalia. La aceleración en el crecimiento de estos NS y su "transformación" en ASGC se produjo a los 10 años de edad promedio, con un diámetro medio de 9 mm. Ningún NS alejado de los forámenes de Monro evolucionó a ASGC. Quince pacientes (68% fueron operados con síntomas de hipertensión endocraneana. La edad media de la cirugía fue 10.8 años. Seis pacientes presentaron déficit visual. En estos últimos, el diámetro medio mayor del tumor fue 31.5 mm, mayor que los 18.7 mm del grupo de pacientes que no presentó secuela visual. El seguimiento clínico imagenológico periódico de toda lesión subependimaria próxima a los agujeros de Monro, permitiría en etapa presintomática anticipar un tratamiento quirúrgico, que reduciría la incidencia de HTE. Estudios prospectivos podrían determinar si el complejo NS-ASGC corresponde a una misma entidad en distinta etapa evolutiva, o son dos lesiones con diferente potencial de crecimiento.The object of this paper is to describe the imaging and clinical characteristics of subependymal nodule (SN - subependymal giant cell astrocytoma (SGCA complex in tuberous sclerosis and analyze its evolution in order to attempt early detection and the prevention of intracranial hypertension. We evaluated 22 patients with

  7. Asbestos as a possible major cause of malignant lung tumors (including small cell carcinoma, adenocarcinoma & mesothelioma), brain tumors (i.e. astrocytoma & glioblastoma multiforme), many other malignant tumors, intractable pain including fibromyalgia, & some cardio-vascular pathology: Safe & effective methods of reducing asbestos from normal & pathological areas.

    Science.gov (United States)

    Omura, Yoshiaki

    2006-01-01

    High incidences of Small Cell Carcinoma & Adenocarcinoma of the lung, Astrocytoma & Glioblastoma Multiforme of the brain and Mesothelioma of the lung were found in those who had a high accumulation of Asbestos in the eyes and upper respiratory system (nose, larynx, trachea, etc.). When measured non-invasively using the Bi-Digital O-Ring Test (BDORT), brain tumors had the highest concentration of Asbestos (0.2 approximately 2.1 mg BDORT units). Relatively high levels of Asbestos (0.2 approximately 0.6 mg BDORT units) were found in: Squamous Cell Carcinoma of the lungs & esophagus, Adenocarcinoma of the larynx & breast, myelogenic leukemia, arteries of these cancers, left ventricle of failing heart, myocardial infarction, some of the narrowed arteries, varicose veins, cataracts, balding heads, hot flashes, Alzheimer's Disease and Autism. A small, round or ellipsoidal area, with diameter of 5 mm or less, was found near the center of every cancer tissue with a higher level of Asbestos (1 approximately 3 mg), As, Zn, Cr and Se, than in the rest of the tumor; this small area may be where the cancer initiated. Among areas of intractable pain with frequent recurrence and gradual worsening, about 0.2 approximately 0.5 mg BDORT units (or higher) of Asbestos were found. The author found that in the Astrocytoma and many other cancer patients, the optimal dose of DHEA produced very significant reductions of cancer cell telomere from over 1400 ng in the brain tumors (and over 900 ng in other cancers) to close to or less than 1 yg (=10(-24) g), with circulatory improvement by reduction of TXB2. Unlike the standard, widely used treatment with DHEA 25 approximately 50 mg daily, which is an overdose; we only gave one optimal dose (1.5 approximately 12.5 mg) and the beneficial effects usually lasted anywhere between 3-6 months, unless inhibiting factors were introduced. In addition, once one optimal dose of DHEA was given, the amount of Asbestos from these tumors decreased very

  8. Cerebellar Pilomyxoid Astrocytoma | Biluts | East and Central African ...

    African Journals Online (AJOL)

    East and Central African Journal of Surgery. Journal Home · ABOUT · Advanced Search · Current Issue · Archives · Journal Home > Vol 21, No 3 (2016) >. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register · Download this PDF file. The PDF file you selected should load ...

  9. Low grade astrocytoma causing dural and calvarial destruction.

    Science.gov (United States)

    Handzhiev, Deyan D; Kalevski, Svetoslav K; Handzhieva, Stanislava V; Dzhenkov, Deyan L; Salieva-Badi, Suna

    2017-06-01

    This case report describes destruction of overlying dura and calvaria by a low grade glioma in the absence of prior surgery or radiation. Bone and dural involving is known to occur with some malignant tumors, but due to low grade glioma is very rare. The initial radiologic examinations demonstrated a heterogeneous mass in the right parietal region with both extra- and intra-axial components. No inward displacement of the adjacent dura was observed. Initial consideration for extra-axial lesions includes metastatic lesions, lymphoma, or an aggressive meningioma. The pathologic findings demonstrated a glial cell origin. To our knowledge, destruction of the dura and calvaria from a low-grade glioma, without prior surgery or radiation, has not been well documented previously. Calvarial destruction with associated intra-axial lesions on imaging may prompt the diagnosis of extra-axial tumors such as aggressive meningiomas, metastasis and lymphoma. We report an unusual case of parietal low-grade glioma with destruction of the dura and calvaria in the absence of prior surgery or radiation. The erosion probably is due to pressure atrophy of the dura and inner table and thinning of the diploe. The mechanism of skull erosion in these superficial gliomas relates to their chronic mass effect (8). The mass displaces the CSF, which normally cushions and diffuses brain pulsations over a wide area. Once the CSF space is effaced, the brain may directly transmit these pulsations to the inner table. Over time, this localized elevated pressure may erode the cortical bone of the inner table. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Cerebellar astrocytoma with extensive lipidization mimicking adipose tissue

    NARCIS (Netherlands)

    Walter, A.; Dingemans, K. P.; Weinstein, H. C.; Troost, D.

    1994-01-01

    We report the case of an elderly woman with a history of headache, vomiting and dizziness while walking. On CT scans a mass was identified in the right cerebellar hemisphere exhibiting radiological characteristics of lipomatous tissue. Surgery revealed a compact lesion consisting of whitish-yellow

  11. Cerebellar Pilomyxoid Astrocytoma | Biluts | East and Central African ...

    African Journals Online (AJOL)

    To increase awareness of PMA within the neurosurgical community, the authors reviewed a case of 11-year-old male child who presented with truncal and cerebellar ataxia and vomiting and right cerebellar tumor diagnosed as PA radiologically but PMA on histopathology examination. These findings indicate that PMA may ...

  12. Glioblastomas, astrocytomas and oligodendrogliomas linked to Lynch syndrome

    DEFF Research Database (Denmark)

    Therkildsen, C; Ladelund, S; Rambech, E

    2015-01-01

    BACKGROUND AND PURPOSE: Brain tumors represent a rare and relatively uncharacterized tumor type in Lynch syndrome. METHODS: The national Danish Hereditary Nonpolyposis Colorectal Cancer Register was utilized to estimate the cumulative life-time risk for brain tumors in Lynch syndrome...... staining suggestive of the IDH1 R132H mutation. CONCLUSION: In Lynch syndrome brain tumors occurred in 14% of the families with significantly higher risks for individuals with MSH2 gene mutations and development of childhood brain tumors in individuals with constitutional MMR defects....

  13. Astrocitoma subependimário de células gigantes em pacientes com esclerose tuberosa: achados em ressonância magnética de dez casos Subependymal giant cell astrocytoma in patients with tuberous sclerosis: magnetic resonance imaging findings in ten cases

    Directory of Open Access Journals (Sweden)

    Karina Takata

    2007-06-01

    Full Text Available OBJETIVO: Relatar os achados de ressonância magnética (RM em 10 casos de astrocitoma subependimário de células gigantes (ASCG em pacientes com esclerose tuberosa (ET. MÉTODO: Foram estudados de forma retrospectiva 10 pacientes com ET e diagnóstico histológico comprovado de ASCG. Quatro pacientes eram do sexo masculino e seis do feminino, com idade média de 15,7 anos. Todos os pacientes foram investigados com RM, sendo os exames revisados por dois radiologistas, havendo decisão por consenso sobre os achados de imagem. Foram analisados os seguintes achados: localização, dimensões, intensidade de sinal em T1/T2, realce pós-contraste e outros achados associados. RESULTADOS: Todos os pacientes apresentaram lesão única sugestiva de ASCG, medindo entre 1,5 cm e 8 cm em seu maior diâmetro. Oito lesões foram encontradas junto ao forame de Monro (80% e duas adjacentes ao corpo do ventrículo lateral (20%. Os tumores apresentavam nas imagens pesadas em T1 médio sinal (70% e em T2 alto sinal (100%, com realce intenso após a administração do gadolínio (100%. CONCLUSÃO: Os astrocitomas subependimários de células gigantes em pacientes com ET em geral apresentam-se como lesão única próxima ao forame de Monro, com médio sinal nas imagens ponderadas em T1, alto sinal em T2 e realce intenso após a administração de contraste.OBJECTIVE: To report the magnetic resonance imaging (MRI findings in 10 patients with subependimal giant cell astrocytoma (SGCA and tuberous sclerosis (TS. METHOD: Ten patients were retrospectively studied, presenting TS and histologically proven SGCA. Four patients were male and six female, with mean age 15.7 years. All patients underwent MRI, which was analyzed by two radiologists, final diagnosis was reached by consensus. The following findings were studied: topography, size, signal intensity on T1/T2-weighted images, contrast enhancement and associated findings. RESULTS: All patients presented a single lesion

  14. Childhood Brain and Spinal Cord Tumors Treatment Overview

    Science.gov (United States)

    ... Choroid glioma of the third ventricle Diffuse astrocytoma, IDH -mutant, IDH -wild type, or NOS Pilocytic astrocytoma Pleomorphic xanthoastrocytoma ... giant cell astrocytoma – High-Grade Astrocytomas Anaplastic astrocytoma, IDH -mutant or IDH -wild type See Childhood Astrocytomas ...

  15. General Information about Childhood Brain and Spinal Cord Tumors

    Science.gov (United States)

    ... Choroid glioma of the third ventricle Diffuse astrocytoma, IDH -mutant, IDH -wild type, or NOS Pilocytic astrocytoma Pleomorphic xanthoastrocytoma ... giant cell astrocytoma – High-Grade Astrocytomas Anaplastic astrocytoma, IDH -mutant or IDH -wild type See Childhood Astrocytomas ...

  16. Erlotinib and Temsirolimus in Treating Patients With Recurrent Malignant Glioma

    Science.gov (United States)

    2015-05-29

    Adult Anaplastic Astrocytoma; Adult Anaplastic Oligodendroglioma; Adult Diffuse Astrocytoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Subependymal Giant Cell Astrocytoma; Recurrent Adult Brain Tumor

  17. A Phase I Study of Mebendazole for the Treatment of Pediatric Gliomas

    Science.gov (United States)

    2017-01-30

    Pilomyxoid Astrocytoma; Pilocytic Astrocytoma; Glioma, Astrocytic; Optic Nerve Glioma; Pleomorphic Xanthoastrocytoma; Glioblastoma Multiforme; Anaplastic Astrocytoma; Gliosarcoma; Diffuse Intrinsic Pontine Glioma; DIPG; Low-grade Glioma; Brainstem Glioma

  18. Sunitinib in Treating Patients With Recurrent Malignant Gliomas

    Science.gov (United States)

    2016-01-29

    Adult Anaplastic Astrocytoma; Adult Diffuse Astrocytoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Pineal Gland Astrocytoma

  19. 18F-FDOPA PET/CT or PET/MRI in Measuring Tumors in Patients With Newly-Diagnosed or Recurrent Gliomas

    Science.gov (United States)

    2017-01-30

    Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Diffuse Astrocytoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Subependymal Giant Cell Astrocytoma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Recurrent Adult Brain Tumor; Recurrent Childhood Anaplastic Astrocytoma; Recurrent Childhood Anaplastic Oligoastrocytoma; Recurrent Childhood Anaplastic Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Diffuse Astrocytoma; Recurrent Childhood Fibrillary Astrocytoma; Recurrent Childhood Gemistocytic Astrocytoma; Recurrent Childhood Giant Cell Glioblastoma; Recurrent Childhood Glioblastoma; Recurrent Childhood Gliomatosis Cerebri; Recurrent Childhood Gliosarcoma; Recurrent Childhood Oligoastrocytoma; Recurrent Childhood Oligodendroglioma; Recurrent Childhood Pilomyxoid Astrocytoma; Recurrent Childhood Protoplasmic Astrocytoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Untreated Childhood Anaplastic Astrocytoma; Untreated Childhood Anaplastic Oligoastrocytoma; Untreated Childhood Anaplastic Oligodendroglioma; Untreated Childhood Brain Stem Glioma; Untreated Childhood Cerebellar Astrocytoma; Untreated Childhood Cerebral Astrocytoma; Untreated Childhood Diffuse Astrocytoma; Untreated Childhood Fibrillary Astrocytoma; Untreated Childhood Gemistocytic Astrocytoma; Untreated Childhood Giant Cell Glioblastoma; Untreated Childhood Glioblastoma; Untreated Childhood Gliomatosis Cerebri; Untreated Childhood Gliosarcoma; Untreated Childhood

  20. The combined incidence of Grade II and Grade IV astrocytoma in the ...

    African Journals Online (AJOL)

    capsaicin, piperine and monosodium glutamate, have excitotoxic, apoptotic or tumourigenic potentials. The focus of this histological study however, is to determine the tumourigenic potentials of Yaji in the brain of rats. Eight weeks old white ...

  1. ABERRANT P53 EXPRESSION DOES NOT CORRELATE WITH THE PROGNOSIS IN ANAPLASTIC ASTROCYTOMA

    NARCIS (Netherlands)

    DANKS, RA; CHOPRA, G; GONZALES, MF; ORIAN, JM; KAYE, AH

    MUTATIONS OF THE p53 tumor-suppressor gene, as determined by the immunohistochemistry of archival formalin-fixed specimens, have been correlated with the prognosis for patients with many different types of malignancy. Similar correlations have been shown in series including patients with all grades

  2. Differential proteomics analysis of low- and high-grade of astrocytoma using iTRAQ quantification

    OpenAIRE

    Ren T; Lin SD; Wang ZF; Shang AJ

    2016-01-01

    Tong Ren,1,* Shide Lin,2,* Zhongfeng Wang,3 Aijia Shang4 1Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, 2Department of Spinal Cord Injury, Institute of Orthopedics and Traumatology of Chinese PLA, General Hospital of Jinan Military Area Command, Jinan, 3State Key Laboratory of Medical Neurobiology, Shanghai Medical College, Fudan University, Shanghai, 4Department of Neurosurgery, General Hospital of Chinese People’s Lib...

  3. Long-term neuropsychologic outcome in children diagnosed with a low-grade astrocytoma

    NARCIS (Netherlands)

    F.K. Aarsen (Femke)

    2012-01-01

    textabstractCentral nervous system (CNS) tumors in children have a relatively high frequency. They are the second most common form of cancer in childhood only exceeded by acute lymphoblastic leukemia (ALL). However, prognosis is more severe and at present more children die because of CNS tumor

  4. Successful Management of Intraoperative Acute Bilateral Pulmonary Embolism in a High Grade Astrocytoma Patient.

    Science.gov (United States)

    Khraise, Wail N; Allouh, Mohammed Z; Hiasat, Mohammad Y; Said, Raed S

    2016-08-31

    BACKGROUND Intraoperative pulmonary embolism (PE) is a rare life-threatening complication in patients undergoing surgical intervention. Generally, cancer patients have a higher risk for developing this complication. Unfortunately, there is no standard procedure for its management. CASE REPORT We report the case of a 39-year-old woman with high-grade glioma in the right frontal lobe who was admitted to the surgical theater for craniotomy and excision of the tumor. During the general anesthesia procedure and just before inserting the central venous line, her end-tidal CO2 and O2 saturation dropped sharply. The anesthesiologist quickly responded with an aggressive resuscitation procedure that included aspiration through the central venous line, 100% O2, and IV administration of ephedrine 6 mg, colloid 500 mL, normal saline 500 mL, and heparin 5000 IU. The patient was extubated and remained in the supine position until she regained consciousness and her vital signs returned to normal. Subsequent radiological examination revealed a massive bilateral PE. A retrievable inferior vena cava (IVC) filter was inserted, and enoxaparin anticoagulant therapy was prescribed to stabilize the patient's condition. After 3 weeks, she underwent an uneventful craniotomy procedure and was discharged a week later under the enoxaparin therapy. CONCLUSIONS The successful management of intraoperative PE requires a quick, accurate diagnosis accompanied with an aggressive, fast response. Anesthesiologists are usually the ones who are held accountable for the diagnosis and early management of this complication. They must be aware of the possibility of such a complication and be ready to react properly and decisively in the operation theater.

  5. Silencing GFAP isoforms in astrocytoma cells disturbs laminin-dependent motility and cell adhesion

    NARCIS (Netherlands)

    Moeton, Martina; Kanski, Regina; Stassen, Oscar M J A; Sluijs, Jacqueline A; Geerts, Dirk; van Tijn, P.; Wiche, Gerhard; van Strien, Miriam E; Hol, Elly M

    Glial fibrillary acidic protein (GFAP) is an intermediate filament protein expressed in astrocytes and neural stem cells. The GFAP gene is alternatively spliced, and expression of GFAP is highly regulated during development, on brain damage, and in neurodegenerative diseases. GFAPα is the canonical

  6. Use of EF5 to Measure the Oxygen Level in Tumor Cells of Patients Undergoing Surgery or Biopsy for Newly Diagnosed Supratentorial Malignant Glioma

    Science.gov (United States)

    2013-01-15

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Diffuse Astrocytoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Subependymoma

  7. Alisertib and Fractionated Stereotactic Radiosurgery in Treating Patients With Recurrent High Grade Gliomas

    Science.gov (United States)

    2017-10-25

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Diffuse Astrocytoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Subependymal Giant Cell Astrocytoma; Recurrent Adult Brain Tumor

  8. Fluorine F 18 Fluorodopa-Labeled PET Scan in Planning Surgery and Radiation Therapy in Treating Patients With Newly Diagnosed High- or Low-Grade Malignant Glioma

    Science.gov (United States)

    2017-11-14

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Diffuse Astrocytoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Subependymal Giant Cell Astrocytoma; Adult Subependymoma

  9. The investigation of changes in proteins expression (Apolipoprotein A1 and albumin in malignant astrocytoma brain tumor

    Directory of Open Access Journals (Sweden)

    Mehrdad Hashemi

    2014-01-01

    Conclusion: The vascular microenvironment of glioma play a major role in determining the pathophysiological character is tics of the tumor. apo A1 and albumin are very significant due to their functional consequences in glioma tumor growth, migration and angiogenesis.

  10. Mitochondrial lactate dehydrogenase is involved in oxidative-energy metabolism in human astrocytoma cells (CCF-STTG1.

    Directory of Open Access Journals (Sweden)

    Joseph Lemire

    Full Text Available Lactate has long been regarded as an end product of anaerobic energy production and its fate in cerebral metabolism has not been precisely delineated. In this report, we demonstrate, for the first time, the ability of a human astrocytic cell line (CCF-STTG1 to consume lactate and to generate ATP via oxidative phosphorylation. (13C-NMR and HPLC analyses aided in the identification of tricarboxylic acid (TCA cyle metabolites and ATP in the astrocytic mitochondria incubated with lactate. Oxamate, an inhibitor of lactate dehydrogenase (LDH, abolished mitochondrial lactate consumption. Electrophoretic and fluorescence microscopic analyses helped localize LDH in the mitochondria. Taken together, this study implicates lactate as an important contributor to ATP metabolism in the brain, a finding that may significantly change our notion of how this important organ manipulates its energy budget.

  11. Multicenter, Phase 1, Dose Escalation Study of Hypofractionated Stereotactic Radiation Therapy With Bevacizumab for Recurrent Glioblastoma and Anaplastic Astrocytoma.

    Science.gov (United States)

    Clarke, Jennifer; Neil, Elizabeth; Terziev, Robert; Gutin, Philip; Barani, Igor; Kaley, Thomas; Lassman, Andrew B; Chan, Timothy A; Yamada, Josh; DeAngelis, Lisa; Ballangrud, Ase; Young, Robert; Panageas, Katherine S; Beal, Kathryn; Omuro, Antonio

    2017-11-15

    To establish the maximum tolerated dose of a 3-fraction hypofractionated stereotactic reirradiation schedule when delivered with concomitant bevacizumab to treat recurrent high-grade gliomas. Patients with recurrent high-grade glioma with Karnofsky performance status ≥60, history of standard fractionated initial radiation, tumor volume at recurrence ≤40 cm3, and absence of brainstem or corpus callosum involvement were eligible. A standard 3+3 phase 1 dose escalation trial design was utilized, with dose-limiting toxicities defined as any grade 3 to 5 toxicities possibly, probably, or definitely related to radiation. Bevacizumab was given at a dose of 10 mg/kg every 2 weeks. Hypofractionated stereotactic reirradiation was initiated after 2 bevacizumab doses, delivered in 3 fractions every other day, starting at 9 Gy per fraction. A total of 3 patients were enrolled at the 9 Gy × 3 dose level cohort, 5 in the 10 Gy × 3 cohort, and 7 in the 11 Gy × 3 cohort. One dose-limiting toxicity of grade 3 fatigue and cognitive deterioration possibly related to hypofractionated stereotactic reirradiation was observed in the 11 Gy × 3 cohort, and this dose was declared the maximum tolerated dose in combination with bevacizumab. Although no symptomatic radionecrosis was observed, substantial treatment-related effects and necrosis were observed in resected specimens. The intent-to-treat median overall survival was 13 months. Reirradiation using a 3-fraction schedule with bevacizumab support is feasible and reasonably well tolerated. Dose-escalation was possible up to 11 Gy × 3, which achieves a near doubling in the delivered biological equivalent dose to normal brain, in comparison with our previous 6 Gy × 5 schedule. Promising overall survival warrants further investigation. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Postoperative neoadjuvant temozolomide before radiotherapy versus standard radiotherapy in patients 60 years or younger with anaplastic astrocytoma or glioblastoma

    DEFF Research Database (Denmark)

    Malmström, Annika; Poulsen, Hans Skovgaard; Grønberg, Bjørn Henning

    2017-01-01

    that NeoTMZ AA patients had a median survival of 95.1 months compared to 35.2 months for RT (p = .022). For patients with GBM, no difference in survival was observed (p = .10). MGMT and IDH status affected outcome. CONCLUSIONS: No advantage of NeoTMZ was noted for the overall study population or subgroup...

  13. Dysphasia and phantosmia as first presentation of multifocal cerebral anaplastic astrocytomas: case report and review of the literatures.

    Science.gov (United States)

    Kong, Xiangyi; Wang, Yu; Liu, Shuai; Lu, Zhaohui; Wu, Huanwen; Mao, Xinxin; Cheng, Xin; Gao, Jun; Guan, Jian; Yang, Yi; Li, Yongning; Xing, Bing; Ma, Wenbin; Wang, Renzhi

    2015-05-01

    Multifocal cerebral gliomas (MCGs) represent approximately 10% of gliomas and are frequently mistaken as metastases of an unknown primary cancer site. Most MCGs are glioblastomas with dysphasia and phantosmia. The disease course, including diagnosis and treatment, is presented and analyzed in detail. The pertinent literature is reviewed regarding this uncommon entity.After an initial impression of brain metastasis from lung cancer because of the magnetic resonance imaging (MRI) resemblance and history of chronic bronchitis, we were able to use positron emission tomography (PET) and excisional biopsy to get the final diagnosis. After 10 months, the patient's overall condition deteriorated and succumbed to his disease.MCGs are easy to be misdiagnosed as metastatic diseases. In addition to MRI, PET adds more biochemical and molecular information and is helpful in the differentiation. Although uncommon, if multiple lesions are present in various locations in the hemispheres, MCG should be kept in mind.

  14. Tipifarnib in Treating Young Patients With Recurrent or Progressive High-Grade Glioma, Medulloblastoma, Primitive Neuroectodermal Tumor, or Brain Stem Glioma

    Science.gov (United States)

    2013-10-07

    Childhood High-grade Cerebral Astrocytoma; Childhood Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

  15. Erlotinib Hydrochloride and Isotretinoin in Treating Patients With Recurrent Malignant Glioma

    Science.gov (United States)

    2017-05-25

    Adult Anaplastic Astrocytoma; Adult Anaplastic Oligodendroglioma; Adult Diffuse Astrocytoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Oligodendroglioma; Recurrent Adult Brain Tumor

  16. Efficacy of 68Ga-DOTATOC Positron Emission Tomography (PET) CT in Children and Young Adults With Brain Tumors

    Science.gov (United States)

    2017-04-27

    Acoustic Schwannoma; Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Meningioma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Choroid Plexus Tumor; Adult Craniopharyngioma; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade I Meningioma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Subependymal Giant Cell Astrocytoma; Adult Subependymoma; Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Childhood Supratentorial Ependymoma; Meningeal Melanocytoma; Newly Diagnosed Childhood Ependymoma; Recurrent Adult Brain Tumor; Recurrent Childhood Anaplastic Astrocytoma; Recurrent Childhood Anaplastic Oligoastrocytoma; Recurrent Childhood Anaplastic Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Diffuse Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Fibrillary Astrocytoma; Recurrent Childhood Gemistocytic Astrocytoma; Recurrent Childhood Giant Cell Glioblastoma; Recurrent Childhood Glioblastoma; Recurrent Childhood Gliomatosis Cerebri; Recurrent Childhood Gliosarcoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood

  17. Palbociclib Isethionate in Treating Younger Patients With Recurrent, Progressive, or Refractory Central Nervous System Tumors

    Science.gov (United States)

    2017-09-27

    Childhood Choroid Plexus Tumor; Childhood Ependymoblastoma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Recurrent Childhood Anaplastic Astrocytoma; Recurrent Childhood Anaplastic Oligoastrocytoma; Recurrent Childhood Anaplastic Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Giant Cell Glioblastoma; Recurrent Childhood Glioblastoma; Recurrent Childhood Gliomatosis Cerebri; Recurrent Childhood Gliosarcoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor

  18. Human U87 astrocytoma cell invasion induced by interaction of βig-h3 with integrin α5β1 involves calpain-2.

    Directory of Open Access Journals (Sweden)

    Jie Ma

    Full Text Available It is known that βig-h3 is involved in the invasive process of many types of tumors, but its mechanism in glioma cells has not been fully clarified. Using immunofluorescent double-staining and confocal imaging analysis, and co-immunoprecipitation assays, we found that βig-h3 co-localized with integrin α5β1 in U87 cells. We sought to elucidate the function of this interaction by performing cell invasion assays and gelatin zymography experiments. We found that siRNA knockdowns of βig-h3 and calpain-2 impaired cell invasion and MMP secretion. Moreover, βig-h3, integrins and calpain-2 are known to be regulated by Ca(2+, and they are also involved in tumor cell invasion. Therefore, we further investigated if calpain-2 was relevant to βig-h3-integrin α5β1 interaction to affect U87 cell invasion. Our data showed that βig-h3 co-localized with integrin α5β1 to enhance the invasion of U87 cells, and that calpain-2, is involved in this process, acting as a downstream molecule.

  19. Decreased Survival of Glioma Patients with Astrocytoma Grade IV (Glioblastoma Multiforme) Associated with Long-Term Use of Mobile and Cordless Phones

    OpenAIRE

    Carlberg, Michael; Hardell, Lennart

    2014-01-01

    On 31 May 2011 the WHO International Agency for Research on Cancer (IARC) categorised radiofrequency electromagnetic fields (RF-EMFs) from mobile phones, and from other devices that emit similar non-ionising electromagnetic fields, as a Group 2B, i.e., a “possible”, human carcinogen. A causal association would be strengthened if it could be shown that the use of wireless phones has an impact on the survival of glioma patients. We analysed survival of 1678 glioma patients in our 1997–2003 and...

  20. Peroxynitrite decomposition catalyst prevents apoptotic cell death in a human astrocytoma cell line incubated with supernatants of HIV-infected macrophages

    Directory of Open Access Journals (Sweden)

    Perno Carlo

    2002-09-01

    Full Text Available Abstract Background Oxidative stress has shown to contribute in the mechanisms underlying apoptotic cell death occuring in AIDS-dementia complex. Here we investigated the role of peroxynitrite in apoptosis occurring in astroglial cells incubated with supernatants of HIV-infected human primary macrophages (M/M. Results Flow cytometric analysis (FACS of human cultured astrocytes shortly incubated with HIV-1-infected M/M supernatants showed apoptotic cell death, an effect accompanied by pronounced staining for nitrotyrosine (footprint of peroxynitrite and by abnormal formation of malondialdehyde (MDA. Pretreatment of astrocytes with the peroxynitrite decomposition catalyst FeTMPS antagonized HIV-related astrocytic apoptosis, MDA formation and nitrotyrosine staining. Conclusions Taken together, our results suggest that inibition of peroxynitrite leads to protection against peroxidative stress accompanying HIV-related apoptosis of astrocytes. Overall results support the role of peroxynitrite in HIV-related programmed death of astrocytes and suggest the use of peroxynitrite decomposition catalyst to counteract HIV-1-related neurological disorders.

  1. Intensity-modulated proton therapy, volumetric-modulated arc therapy, and 3D conformal radiotherapy in anaplastic astrocytoma and glioblastoma. A dosimetric comparison

    Energy Technology Data Exchange (ETDEWEB)

    Adeberg, S.; Debus, J. [Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg (Germany); Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg (Germany); University Hospital Heidelberg, Department of Radiation Oncology, Heidelberg (Germany); German Cancer Research Center (DKFZ), Clinical Cooperation Unit Radiation Oncology, Heidelberg (Germany); Harrabi, S.B.; Bougatf, N.; Rieber, J.; Koerber, S.A.; Herfarth, K.; Rieken, S. [Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg (Germany); Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg (Germany); University Hospital Heidelberg, Department of Radiation Oncology, Heidelberg (Germany); Bernhardt, D.; Syed, M.; Sprave, T.; Mohr, A. [Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg (Germany); University Hospital Heidelberg, Department of Radiation Oncology, Heidelberg (Germany); Abdollahi, A. [University Hospital Heidelberg, Department of Radiation Oncology, Heidelberg (Germany); Haberer, T. [Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg (Germany); Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg (Germany); Combs, S.E. [Technische Universitaet Muenchen, Department of Radiation Oncology, Muenchen (Germany); Helmholtz Zentrum Muenchen, Institut fuer Innovative Radiotherapie (iRT), Department of Radiation Sciences (DRS), Neuherberg (Germany)

    2016-11-15

    The prognosis for high-grade glioma (HGG) patients is poor; thus, treatment-related side effects need to be minimized to conserve quality of life and functionality. Advanced techniques such as proton radiation therapy (PRT) and volumetric-modulated arc therapy (VMAT) may potentially further reduce the frequency and severity of radiogenic impairment. We retrospectively assessed 12 HGG patients who had undergone postoperative intensity-modulated proton therapy (IMPT). VMAT and 3D conformal radiotherapy (3D-CRT) plans were generated and optimized for comparison after contouring crucial neuronal structures important for neurogenesis and neurocognitive function. Integral dose (ID), homogeneity index (HI), and inhomogeneity coefficient (IC) were calculated from dose statistics. Toxicity data were evaluated. Target volume coverage was comparable for all three modalities. Compared to 3D-CRT and VMAT, PRT showed statistically significant reductions (p < 0.05) in mean dose to whole brain (-20.2 %, -22.7 %); supratentorial (-14.2 %, -20,8 %) and infratentorial (-91.0 %, -77.0 %) regions; brainstem (-67.6 %, -28.1 %); pituitary gland (-52.9 %, -52.5 %); contralateral hippocampus (-98.9 %, -98.7 %); and contralateral subventricular zone (-62.7 %, -66.7 %, respectively). Fatigue (91.7 %), radiation dermatitis (75.0 %), focal alopecia (100.0 %), nausea (41.7 %), cephalgia (58.3 %), and transient cerebral edema (16.7 %) were the most common acute toxicities. Essential dose reduction while maintaining equal target volume coverage was observed using PRT, particularly in contralaterally located critical neuronal structures, areas of neurogenesis, and structures of neurocognitive functions. These findings were supported by preliminary clinical results confirming the safety and feasibility of PRT in HGG. (orig.) [German] Die Prognose bei ''High-grade''-Gliomen (HGG) ist infaust. Gerade bei diesen Patienten sollten therapieassoziierte Nebenwirkungen minimiert werden, um die Lebensqualitaet und Funktionalitaet zu erhalten. Moderne Radiotherapietechniken, wie die Protonenradiotherapie (PRT) und die volumenmodulierte Arc-Therapie (VMAT), haben das Potential, die Dosisbelastung von Risikoorganen weiter zu reduzieren. 12 HGG-Patienten, die eine postoperative intensitaetsmodulierten Protonentherapie (IMPT) erhalten hatten, wurden retrospketiv bewertet. Zum Vergleich wurden VMAT- und 3D-konformale Radiotherapieplaene (3D-CRT) generiert, in denen die Dosisverteilung in wichtigen Arealen der Neurogenese und neurokognitiven Funktion bestimmt wurden. Anhand von Dosisstatistiken wurden die Integraldosis (ID), der Homogenitaetsindex (HI) und der Inhomogenitaetskoeffizient (IC) berechnet und die therapieassoziierte Toxizitaet bestimmt. Fuer alle drei Techniken war die Zielvolumenabdeckung vergleichbar gut. PRT reduzierte die D{sub mean} im Vergleich zur 3D-CRT und VMAT im Ganzhirn (-20,2 %; -22,7 %), im supratentoriellen (-14,2 %; -20,8 %) und infratentoriellen Hirn (-91 %; -77,0 %), im Hirnstamm (-67,6 %; -28, %), in der Hypophyse (-52,9 %; -52,5 %), im kontralateralen Hippokampus (-98,9 %; -98,7 %) und in der kontralateralen subventrikulaeren Zone (-62,7 %; -66,7 %) signifikant (p < 0,05). Die haeufigsten akuten Nebenwirkungen waren Fatigue (91,7 %), radiogene Dermatitis (75,0 %), fokale Alopezie (100,0 %), Nausea (41,7 %), Cephalgien (58,3 %) und voruebergehende zerebrale Oedeme (16,7 %). Durch die PRT konnte bei Aufrechterhaltung der Zielvolumenabdeckung eine signifikante Dosisreduktion insbesondere in kontralateralen kritischen neuronalen Strukturen sowie in essentiellen Arealen fuer die neurokognitiven Funktionen und Neurogenese beobachtet werden. Die vorlaeufigen klinischen Ergebnisse bestaetigen die sichere Durchfuehrbarkeit und Praktikabilitaet der PRT bei HGG. (orig.)

  2. Bortezomib sensitizes primary human astrocytoma cells of WHO grades I to IV for tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis

    NARCIS (Netherlands)

    Koschny, Ronald; Holland, Heidrun; Sykora, Jaromir; Haas, Tobias L.; Sprick, Martin R.; Ganten, Tom M.; Krupp, Wolfgang; Bauer, Manfred; Ahnert, Peter; Meixensberger, Jürgen; Walczak, Henning

    2007-01-01

    Malignant gliomas are the most aggressive human brain tumors without any curative treatment. The antitumor effect of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in gliomas has thus far only been thoroughly established in tumor cell lines. In the present study, we investigated the

  3. Perfusion MRI (dynamic susceptibility contrast imaging) with different measurement approaches for the evaluation of blood flow and blood volume in human gliomas

    DEFF Research Database (Denmark)

    Thomsen, H; Steffensen, E; Larsson, Elna-Marie

    2012-01-01

    CBV maps, with contralateral normal appearing white matter and cerebellum as reference regions. Larger ROIs were drawn for histogram analyses. The type and grade of the gliomas were obtained by histopathology. Statistical comparison was made between diffuse astrocytomas, anaplastic astrocytomas...

  4. Cysts

    Science.gov (United States)

    ... of Tumors Astrocytoma Atypical Teratoid Rhaboid Tumor (ATRT) Chondrosarcoma Choroid Plexus Craniopharyngioma Cysts Ependymoma Germ Cell Tumor ... of Tumors Astrocytoma Atypical Teratoid Rhaboid Tumor (ATRT) Chondrosarcoma Choroid Plexus Craniopharyngioma Cysts Ependymoma Germ Cell Tumor ...

  5. Glioblastoma

    Science.gov (United States)

    ... of Tumors Astrocytoma Atypical Teratoid Rhaboid Tumor (ATRT) Chondrosarcoma Choroid Plexus Craniopharyngioma Cysts Ependymoma Germ Cell Tumor ... of Tumors Astrocytoma Atypical Teratoid Rhaboid Tumor (ATRT) Chondrosarcoma Choroid Plexus Craniopharyngioma Cysts Ependymoma Germ Cell Tumor ...

  6. Oligoastrocytoma

    Science.gov (United States)

    ... of Tumors Astrocytoma Atypical Teratoid Rhaboid Tumor (ATRT) Chondrosarcoma Choroid Plexus Craniopharyngioma Cysts Ependymoma Germ Cell Tumor ... of Tumors Astrocytoma Atypical Teratoid Rhaboid Tumor (ATRT) Chondrosarcoma Choroid Plexus Craniopharyngioma Cysts Ependymoma Germ Cell Tumor ...

  7. Oligodendroglioma

    Science.gov (United States)

    ... of Tumors Astrocytoma Atypical Teratoid Rhaboid Tumor (ATRT) Chondrosarcoma Choroid Plexus Craniopharyngioma Cysts Ependymoma Germ Cell Tumor ... of Tumors Astrocytoma Atypical Teratoid Rhaboid Tumor (ATRT) Chondrosarcoma Choroid Plexus Craniopharyngioma Cysts Ependymoma Germ Cell Tumor ...

  8. Choroid Plexus

    Science.gov (United States)

    ... of Tumors Astrocytoma Atypical Teratoid Rhaboid Tumor (ATRT) Chondrosarcoma Choroid Plexus Craniopharyngioma Cysts Ependymoma Germ Cell Tumor ... of Tumors Astrocytoma Atypical Teratoid Rhaboid Tumor (ATRT) Chondrosarcoma Choroid Plexus Craniopharyngioma Cysts Ependymoma Germ Cell Tumor ...

  9. Schwannoma

    Science.gov (United States)

    ... of Tumors Astrocytoma Atypical Teratoid Rhaboid Tumor (ATRT) Chondrosarcoma Choroid Plexus Craniopharyngioma Cysts Ependymoma Germ Cell Tumor ... of Tumors Astrocytoma Atypical Teratoid Rhaboid Tumor (ATRT) Chondrosarcoma Choroid Plexus Craniopharyngioma Cysts Ependymoma Germ Cell Tumor ...

  10. Medulloblastoma

    Science.gov (United States)

    ... of Tumors Astrocytoma Atypical Teratoid Rhaboid Tumor (ATRT) Chondrosarcoma Choroid Plexus Craniopharyngioma Cysts Ependymoma Germ Cell Tumor ... of Tumors Astrocytoma Atypical Teratoid Rhaboid Tumor (ATRT) Chondrosarcoma Choroid Plexus Craniopharyngioma Cysts Ependymoma Germ Cell Tumor ...

  11. Glioma

    Science.gov (United States)

    ... of Tumors Astrocytoma Atypical Teratoid Rhaboid Tumor (ATRT) Chondrosarcoma Choroid Plexus Craniopharyngioma Cysts Ependymoma Germ Cell Tumor ... of Tumors Astrocytoma Atypical Teratoid Rhaboid Tumor (ATRT) Chondrosarcoma Choroid Plexus Craniopharyngioma Cysts Ependymoma Germ Cell Tumor ...

  12. Craniopharyngioma

    Science.gov (United States)

    ... of Tumors Astrocytoma Atypical Teratoid Rhaboid Tumor (ATRT) Chondrosarcoma Choroid Plexus Craniopharyngioma Cysts Ependymoma Germ Cell Tumor ... of Tumors Astrocytoma Atypical Teratoid Rhaboid Tumor (ATRT) Chondrosarcoma Choroid Plexus Craniopharyngioma Cysts Ependymoma Germ Cell Tumor ...

  13. Pituitary Tumors

    Science.gov (United States)

    ... of Tumors Astrocytoma Atypical Teratoid Rhaboid Tumor (ATRT) Chondrosarcoma Choroid Plexus Craniopharyngioma Cysts Ependymoma Germ Cell Tumor ... of Tumors Astrocytoma Atypical Teratoid Rhaboid Tumor (ATRT) Chondrosarcoma Choroid Plexus Craniopharyngioma Cysts Ependymoma Germ Cell Tumor ...

  14. Ependymoma

    Science.gov (United States)

    ... of Tumors Astrocytoma Atypical Teratoid Rhaboid Tumor (ATRT) Chondrosarcoma Choroid Plexus Craniopharyngioma Cysts Ependymoma Germ Cell Tumor ... of Tumors Astrocytoma Atypical Teratoid Rhaboid Tumor (ATRT) Chondrosarcoma Choroid Plexus Craniopharyngioma Cysts Ependymoma Germ Cell Tumor ...

  15. Proton Beam Radiation Therapy in Treating Patients With Low Grade Gliomas

    Science.gov (United States)

    2015-12-14

    Adult Brain Tumor; Adult Brain Stem Glioma; Adult Diffuse Astrocytoma; Adult Ependymoma; Adult Grade II Meningioma; Adult Melanocytic Lesion; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Pineal Gland Astrocytoma; Adult Pineocytoma; Recurrent Adult Brain Tumor

  16. Phase I Study of Cellular Immunotherapy for Recurrent/Refractory Malignant Glioma Using Intratumoral Infusions of GRm13Z40-2, An Allogeneic CD8+ Cytolitic T-Cell Line Genetically Modified to Express the IL 13-Zetakine and HyTK and to be Resistant to Glucocorticoids, in Combination With Interleukin-2

    Science.gov (United States)

    2015-06-03

    Anaplastic Astrocytoma; Anaplastic Ependymoma; Anaplastic Meningioma; Anaplastic Oligodendroglioma; Brain Stem Glioma; Ependymoblastoma; Giant Cell Glioblastoma; Glioblastoma; Gliosarcoma; Grade III Meningioma; Meningeal Hemangiopericytoma; Mixed Glioma; Pineal Gland Astrocytoma; Brain Tumor

  17. RO4929097, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Malignant Glioma

    Science.gov (United States)

    2015-09-28

    Acoustic Schwannoma; Adult Anaplastic (Malignant) Meningioma; Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Brain Stem Glioma; Adult Choroid Plexus Neoplasm; Adult Craniopharyngioma; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade I Meningioma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Primary Melanocytic Lesion of Meninges; Adult Subependymal Giant Cell Astrocytoma; Adult Subependymoma; Adult Supratentorial Primitive Neuroectodermal Tumor; Malignant Adult Intracranial Hemangiopericytoma

  18. Clinical evidence of the role of the cerebellum in the suppression of overt articulatory movements during reading. A study of reading in children and adolescents treated for cerebellar pilocytic astrocytoma.

    Science.gov (United States)

    Ait Khelifa-Gallois, N; Puget, S; Longaud, A; Laroussinie, F; Soria, C; Sainte-Rose, C; Dellatolas, G

    2015-04-01

    It has been suggested that the cerebellum is involved in reading acquisition and in particular in the progression from automatic grapheme-phoneme conversion to the internalization of speech required for silent reading. This idea is in line with clinical and neuroimaging data showing a cerebellar role in subvocal rehearsal for printed verbalizable material and with computational "internal models" of the cerebellum suggesting its role in inner speech (i.e. covert speech without mouthing the words). However, studies examining a possible cerebellar role in the suppression of articulatory movements during silent reading acquisition in children are lacking. Here, we report clinical evidence that the cerebellum plays a part in this transition. Reading performances were compared between a group of 17 paediatric patients treated for benign cerebellar tumours and a group of controls matched for age, gender, and parental socio-educational level. The patients scored significantly lower on all reading, but the most striking difference concerned silent reading, perfectly acquired by almost all controls, contrasting with 41 % of the patients who were unable to read any item silently. Silent reading was correlated with the Working Memory Index. The present findings converge with previous reports on an implication of the cerebellum in inner speech and in the automatization of reading. This cerebellar implication is probably not specific to reading, as it also seems to affect non-reading tasks such as counting.

  19. Yoga Therapy in Treating Patients With Malignant Brain Tumors

    Science.gov (United States)

    2017-07-27

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Meningioma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Choroid Plexus Tumor; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Recurrent Adult Brain Tumor

  20. Gadobutrol Versus Gadopentetate Dimeglumine or Gadobenate Dimeglumine Before DCE-MRI in Diagnosing Patients With Multiple Sclerosis, Grade II-IV Glioma, or Brain Metastases

    Science.gov (United States)

    2017-03-22

    Adult Anaplastic (Malignant) Meningioma; Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Choroid Plexus Neoplasm; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Primary Melanocytic Lesion of Meninges; Adult Supratentorial Primitive Neuroectodermal Tumor; Malignant Adult Intracranial Hemangiopericytoma; Metastatic Malignant Neoplasm in the Brain; Multiple Sclerosis; Recurrent Adult Brain Neoplasm

  1. Overexpression of Eg5 correlates with high grade astrocytic neoplasm.

    Science.gov (United States)

    Liu, Liqiong; Liu, Xichun; Mare, Marcus; Dumont, Aaron S; Zhang, Haitao; Yan, Dong; Xiong, Zhenggang

    2016-01-01

    To investigate the relationship between Eg5 and histopathological grade of astrocytoma, Eg5 expression was evaluated by immunohistochemical examination on 88 specimens including 25 cases of glioblastoma (WHO grade IV), 22 cases of anaplastic astrocytoma (WHO grade III), 20 cases of diffuse astrocytoma (WHO grade II), and 21 cases of pilocytic astrocytoma (WHO grade I). The histopathological characteristics and Eg5 expression level of each tumor were assessed and statistically analyzed. Astrocytic tumors exhibited significant correlation of expression of Eg5 with higher WHO histopathological grades (p neoplasm, and it may represent an independent diagnostic and prognostic factor in grading astrocytic tumors and predicting prognosis of astrocytic tumor patients.

  2. p28 in Treating Younger Patients With Recurrent or Progressive Central Nervous System Tumors

    Science.gov (United States)

    2017-08-03

    Teratoid Tumor, Atypical; Choroid Plexus Neoplasms; Anaplastic Astrocytoma; Anaplastic Oligodendroglioma; Brainstem Tumors; Giant Cell Glioblastoma; Glioblastoma; Gliosarcoma; Medulloblastoma; Neuroectodermal Tumor, Primitive

  3. Bevacizumab and Irinotecan in Treating Young Patients With Recurrent, Progressive, or Refractory Glioma, Medulloblastoma, Ependymoma, or Low Grade Glioma

    Science.gov (United States)

    2017-10-23

    Childhood Cerebral Anaplastic Astrocytoma; Childhood Oligodendroglioma; Childhood Spinal Cord Neoplasm; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma

  4. Collecting and Storing Blood and Brain Tumor Tissue Samples From Children With Brain Tumors

    Science.gov (United States)

    2016-11-21

    Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Newly Diagnosed Childhood Ependymoma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma

  5. A PROSPECTIVE HISTOPATHOLOGICAL-BASED STUDY OF BRAIN TUMOURS IN A REFERRAL CENTRE

    National Research Council Canada - National Science Library

    Prathima Gujjaru; N. Saila Rekha; Syam Sunder Rao Uttarakar

    2016-01-01

    .... Most of the tumours encountered are not related to any identifiable risk factors except for irradiation and some hereditary syndromes like subependymal giant cell astrocytoma, glioblastoma multiforme...

  6. Glioblastoma following radiotherapy in a patient with tuberous sclerosis. Case report

    Energy Technology Data Exchange (ETDEWEB)

    Matsumura, Hirotaka; Takimoto, Hiroshi; Shimada, Nobumitsu; Hirata, Masayuki [Suita Municipal Hospital, Osaka (Japan); Ohnishi, Takanori; Hayakawa, Toru

    1998-05-01

    A 26-year-old male with tuberous sclerosis developed a glioblastoma in the right temporal lobe 8 years after surgical excision and irradiation of a subependymal giant cell astrocytoma. The glioblastoma was probably an irradiation-induced tumor. Irradiation should not be given routinely for subependymal giant cell astrocytoma. (author)

  7. Astroglial c-Myc overexpression predisposes mice to primary malignant gliomas

    DEFF Research Database (Denmark)

    Jensen, Niels Aagaard; Pedersen, Karen-Marie; Lihme, Frederikke

    2003-01-01

    Malignant astrocytomas are common human primary brain tumors that result from neoplastic transformation of astroglia or their progenitors. Here we show that deregulation of the c-Myc pathway in developing astroglia predisposes mice to malignant astrocytomas within 2-3 weeks of age. The genetically...

  8. Role of proton magnetic resonance spectroscopy in diagnosis of ...

    African Journals Online (AJOL)

    Mohammed Mahmoud Donia

    2012-01-23

    Jan 23, 2012 ... Aim of the work: To study the role of proton magnetic resonance spectroscopy in diagnosis of pil- ocytic astrocytoma in children. Subjects and methods: This study included seven pediatric patients with histopathologically proven pilocytic astrocytoma. All patients were subjected to full history taking and ...

  9. Role of proton magnetic resonance spectroscopy in diagnosis of ...

    African Journals Online (AJOL)

    Background: Pilocytic astrocytomas are the second overall most common pediatric brain tumor. Magnetic resonance (MR) imaging is widely used in the diagnosis and follow up of pediatric patients with pilocytic astrocytomas because of its ability to provide anatomical detail. However conventional MR imaging does not ...

  10. Gliomatosis cerebri--an appropriate diagnosis? Case reports

    DEFF Research Database (Denmark)

    Fallentin, E; Skriver, E; Herning, Gudrun Margrethe

    1997-01-01

    PURPOSE: To evaluate the premises for the diagnosis gliomatosis cerebri in relation to diffuse astrocytomas. MATERIAL AND METHODS: CT, MR images and pathological analyses were used to assess the cases of 4 patients with diffusely infiltrating astrocytic tumours that radiologically, clinically...... and pathologically resembled gliomatosis cerebri. RESULTS AND CONCLUSION: Some astrocytomas have an immense potential for diffuse infiltration and they would seem to be more frequent than recognized hitherto. The definition of gliomatosis cerebri as a separate entity is questionable, and a diagnosis of diffusely...... infiltrating astrocytoma is recommended in such cases...

  11. Early genetic changes involved in low-grade astrocytic tumor development.

    Science.gov (United States)

    Arjona, Dolores; Rey, Juan Antonio; Taylor, Shirley M

    2006-09-01

    Astrocytomas represent the most common form of glial tumors. The most malignant grade of these tumors, glioblastoma multiforme, may arise as a malignant progression from low-grade astrocytoma through anaplastic astrocytoma to secondary GBM, or else it may arise "de novo" as primary GBM. Both types of glioblastoma are usually histologically indistinguishable. However, distinct molecular alterations have been described between them that potentially allow differentiation between the two mechanisms of origin. Since malignant transformation is a multistep process, we summarize in this review the earliest genetic changes that seem to be involved in the appearance and development of low-grade astrocytic tumors, where early detection and treatment could be possible.

  12. Optic glioma

    Science.gov (United States)

    Glioma - optic; Optic nerve glioma; Juvenile pilocytic astrocytoma; Brain cancer - optic glioma ... Optic gliomas are rare. The cause of optic gliomas is unknown. Most optic gliomas are slow-growing ...

  13. Experiment list: SRX377962 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available SRX377962 hg19 TFs and others CHD4 Neural Glioblastoma MeSH Description=A malignant form of astrocytoma hist...ologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage,

  14. Experiment list: SRX377960 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available tologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage...SRX377960 hg19 TFs and others ZFHX4 Neural Glioblastoma MeSH Description=A malignant form of astrocytoma his

  15. Experiment list: SRX377963 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available SRX377963 hg19 TFs and others CHD4 Neural Glioblastoma MeSH Description=A malignant form of astrocytoma hist...ologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage,

  16. Experiment list: SRX377961 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available tologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage...SRX377961 hg19 TFs and others ZFHX4 Neural Glioblastoma MeSH Description=A malignant form of astrocytoma his

  17. Spectrum of intracranial tumours in a tertiary health carefacility: Our ...

    African Journals Online (AJOL)

    Medulloblastoma accounted for 18%.(10).Of the cases of Gliomas, majority(52%) fell under WHO grade II. (38%)of the Meningioma were of the mixed type while 25% had transitional type. Conclusion: astrocytomas was the commonest brain tumour.

  18. Diagnosis, monitoring and treatment of tuberous sclerosis complex ...

    African Journals Online (AJOL)

    mammalian target of rapamycin) inhibitors to treat subependymal giant cell astrocytomas not amenable to surgery and renal angiomyolipomas larger than 3 cm, and as adjunctive treatment for refractory focal seizures. We await with interest results from ...

  19. A Pilot Feasibility Study of Oral 5-Fluorocytosine and Genetically-Modified Neural Stem Cells Expressing E.Coli Cytosine Deaminase for Treatment of Recurrent High Grade Gliomas

    Science.gov (United States)

    2017-11-07

    Adult Anaplastic Astrocytoma; Recurrent Grade III Glioma; Recurrent Grade IV Glioma; Adult Anaplastic Oligodendroglioma; Adult Brain Tumor; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Recurrent Adult Brain Tumor; Adult Anaplastic Oligoastrocytoma; Recurrent High Grade Glioma

  20. "Suicide" Gen Therapy for Malignant Central Nervous System Tumors

    NARCIS (Netherlands)

    A.J.P.E. Vincent (Arnoud)

    1998-01-01

    textabstractDespite development in surgical techniques, chemotherapy and radiotherapy, most malignancies of the central nervous system are still devastating tumors with a poor prognosis. For example, median survival of patients with malignant gliomas (astrocytoma, oligodendroglioma or mixed rype) is

  1. Experiment list: SRX103002 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage,...SRX103002 hg19 TFs and others CTCF Neural Glioblastoma MeSH Description=A malignant form of astrocytoma hist

  2. Bafetinib in Treating Patients With Recurrent High-Grade Glioma or Brain Metastases

    Science.gov (United States)

    2013-03-18

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Recurrent Adult Brain Tumor; Tumors Metastatic to Brain; Adult Anaplastic Oligoastrocytoma

  3. Phase II Pediatric Study With Dabrafenib in Combination With Trametinib in Patients With HGG

    Science.gov (United States)

    2018-01-24

    Anaplastic Astrocytoma; Glioblastoma; Giant Cell Glioblastoma; Gliosarcoma; Anaplastic Oligodendroglioma; Anaplastic Oligoastrocytoma; Anaplastic Ependymoma; Choroid Plexus Carcinoma; Anaplastic Ganglioglioma; Pineal Parenchymal Tumor; Pineoblastoma; Medulloblastoma; PNET; Rhabdoid Tumor; Perineurioma; MPNST; Malignant Meningloma; Anaplastic Hemangiopericytoma

  4. Dolor cervical incoercible

    Directory of Open Access Journals (Sweden)

    Adrián F Narváez-Muñoz

    2014-03-01

    Astrocytomas are relatively common glial neoplasm of the central nervous system, but only a small percentage of them are located in the spinal cord, with a predilection for the cervical and dorsal regions. In most cases, extend longitudinally, affecting several cord segments. Pain is a frequent symptom of local character bone segments involving the tumor, associated with sensory deficit and / or motor. The following is the case of a 60 year old woman with cervical cord astrocytoma extended to the brainstem.

  5. Candidate genes for the progression of malignant gliomas identified by microarray analysis.

    Science.gov (United States)

    Bozinov, Oliver; Köhler, Sylvia; Samans, Birgit; Benes, Ludwig; Miller, Dorothea; Ritter, Markus; Sure, Ulrich; Bertalanffy, Helmut

    2008-01-01

    Malignant astrocytomas of World Health Organization (WHO) grade III or IV have a reduced median survival time, and possible pathways have been described for the progression of anaplastic astrocytomas and glioblastomas, but the molecular basis of malignant astrocytoma progression is still poorly understood. Microarray analysis provides the chance to accelerate studies by comparison of the expression of thousands of genes in these tumours and consequently identify targeting genes. We compared the transcriptional profile of 4,608 genes in tumours of 15 patients including 6 anaplastic astrocytomas (WHO grade III) and 9 glioblastomas (WHO grade IV) using microarray analysis. The microarray data were corroborated by real-time reverse transcription-polymerase chain reaction analysis of two selected genes. We identified 166 gene alterations with a fold change of 2 and higher whose mRNA levels differed (absolute value of the t statistic of 1.96) between the two malignant glioma groups. Further analyses confirmed same transcription directions for Olig2 and IL-13Ralpha2 in anaplastic astrocytomas as compared to glioblastomas. Microarray analyses with a close binary question reveal numerous interesting candidate genes, which need further histochemical testing after selection for confirmation. IL-13Ralpha2 and Olig2 have been identified and confirmed to be interesting candidate genes whose differential expression likely plays a role in malignant progression of astrocytomas.

  6. Tbx2 confers poor prognosis in glioblastoma and promotes temozolomide resistance with change of mitochondrial dynamics

    Science.gov (United States)

    Yi, Fuxin; Du, Jianzhou; Ni, Weimin; Liu, Weixian

    2017-01-01

    Tbx2 is a cancer-related protein that was found to be overexpressed in several human malignancies. The present study aims to investigate the clinical significance and biological role of Tbx2 in human astrocytoma. We examined its protein expression in 102 cases of astrocytoma tissues using immunohistochemical staining. Negative Tbx2 staining was observed in normal astrocytes, and positive nuclear staining was found in 41 out of 102 astrocytoma specimens. The rate of Tbx2 overexpression in pylocytic astrocytoma, diffuse astrocytoma, anaplastic astrocytoma, and glioblastoma multiform (GBM) were 0%, 26.1%, 40%, and 52%, respectively. Tbx2 overexpression correlated with poor prognosis in patients with astrocytoma or GBM. Tbx2 plasmid transfection was performed in A172 cells, and Tbx2 siRNA knockdown was carried out in U251 cells. Cell Counting Kit-8, cell cycle analysis, and matrigel invasion assay showed that Tbx2 overexpression upregulated cell proliferation, G1-S transition, and invasion, with corresponding change of cyclin D1, p21, and MMP 2 and 9. Importantly, we demonstrated that Tbx2 reduced apoptosis and conferred resistance to temozolomide in GBM cell lines. Further experiments showed that Tbx2 could regulate mitochondrial fission/fusion balance. Western blot showed that Tbx2 overexpression reduced caspase 3 cleavage, while it induced Bcl-2 and p-Drp1 upregulation. In conclusion, our results indicated that Tbx2 might serve as an indicator for poor prognosis and also be useful as an important therapeutic in human GBM, which inhibits apoptosis through regulation of mitochondrial function. PMID:28260920

  7. Imaging of adult astrocytic brain tumours with 7 T MRI: preliminary results

    Energy Technology Data Exchange (ETDEWEB)

    Moenninghoff, Christoph; Forsting, Michael; Wanke, Isabel [University Hospital Essen, Department of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); University Duisburg-Essen, Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen (Germany); Maderwald, Stefan; Theysohn, Jens M.; Kraff, Oliver; Ladd, Mark E. [University Duisburg-Essen, Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen (Germany); University Hospital Essen, Department of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); El Hindy, Nicolai [University Hospital Essen, Department of Neurosurgery, Essen (Germany); Nes, Johannes van de [University Hospital Essen, Department of Neuropathology, Essen (Germany)

    2010-03-15

    In this study tumour vascularity and necrosis of intracranial astrocytomas were compared using 7 T and 1.5 T magnetic resonance imaging (MRI). Fifteen patients with histologically proven astrocytomas (WHO grades II-IV) were prospectively examined at 1.5 T (Magnetom Espree or Sonata) and 7 T (Magnetom 7 T, Siemens, Erlangen, Germany) with T2*-w (weighted), T1-w with (only a subset of five patients at 7 T) and without contrast medium, T2-w and proton-density (PD)-w MRI. Clinically used 1.5 T sequences were adapted to 7 T. Histological findings and T2*-w MR images at both field strengths were compared for the presence of assumed tumour microvascularity and necrosis. Two diffusely infiltrating astrocytomas, four anaplastic astrocytomas and nine glioblastomas were included. T2*-w images depicted susceptibility patterns representing presumed tumour microvascularity in 8 out of 15 (53%) gliomas at 7 T compared with 5 out of 15 (33%) gliomas at 1.5 T. Compared with 1.5 T MRI three additional necrotic tumour areas were depicted only on 7 T T2- and T2*-w images of one glioblastoma. On T1-w MR images, contrast enhancement of five out of five glioblastomas was similar at both field strengths. 7 T gradient-echo sequences provide excellent image contrast of presumed microvasculature and necrosis in astrocytomas. (orig.)

  8. Treatments of intramedullary spinal cord tumors

    Energy Technology Data Exchange (ETDEWEB)

    Ueyama, Kazumasa; Okada, Akihiro; Echigoya, Naoki; Yokoyama, Toru; Harata, Seiko [Hirosaki Univ., Aomori (Japan). School of Medicine

    2001-04-01

    In order to establish a treatment for intramedullary spinal cord tumors, histology, symptoms (preoperative, upon discharge from the hospital, and at the final follow-up examination), postoperative combination therapy, postoperative complications, and recurrence were assessed in patients with intramedullary spinal cord tumors treated in the author's hospital during the past 19 years. There were 26 subjects (astrocytoma in 8, ependymoma in 6, intramedullary neurinoma in 3, lipoma in 3, hemangioblastoma in 3, cavernous angioma in 1, capillary hemangioma in 1, and enterogenous cyst in 1). Surgery had been performed in 24 of them, and 7 of the tumors were completely resected, 6 were incompletely resected, and 3 were partially resected. Radiotherapy had been performed to treat 7 astrocytomas and 2 ependymomas. Kyphosis was noted as a postoperative complication in 1 patient with an astrocytoma who had received postoperative radiotherapy. Postoperative improvement was better in the patients who had the ependymomas, lipoma, and angioma, and in 1 patient with an astrocytoma. The astrocytomas were very difficult to completely remove surgically, and postoperative radiotherapy was thought to be indispensable. The ependymomas, hemangioblastomas, and angiomas could be surgically resected, but the surgeon must has to exercise sufficient care during the operation. The lipomas were also difficult to resect surgically and intratumoral decompression or decompression should be performed. For adolescents spinal deformity should be considered as one of the postoperative complications. (K.H.)

  9. Established and emerging variants of glioblastoma multiforme: review of morphological and molecular features.

    Science.gov (United States)

    Karsy, Michael; Gelbman, Marshall; Shah, Paarth; Balumbu, Odessa; Moy, Fred; Arslan, Erol

    2012-01-01

    Since the recent publication of the World Health Organization brain tumour classification guidelines in 2007, a significant expansion in the molecular understanding of glioblastoma multiforme (GBM) and its pathological as well as genomic variants has been evident. The purpose of this review article is to evaluate the histopathological, molecular and clinical features surrounding emerging and currently established GBM variants. The tumours discussed include classic glioblastoma multiforme and its four genomic variants, proneural, neural, mesenchymal, classical, as well as gliosarcoma (GS), and giant cell GBM (gcGBM). Furthermore, the emerging variants include fibrillary/epithelial GBM, small cell astrocytoma (SCA), GBM with oligodendroglial component (GBMO), GBM with primitive neuroectodermal features (GBM-PNET), gemistocytic astrocytoma (GA), granular cell astrocytoma (GCA), and paediatric high-grade glioma (HGG) as well as diffuse intrinsic pontine glioma (DIPG). Better understanding of the heterogeneous nature of GBM may provide improved treatment paradigms, prognostic classification, and approaches towards molecularly targeted treatments.

  10. Transferrin receptor-1 and ferritin heavy and light chains in astrocytic brain tumors

    DEFF Research Database (Denmark)

    Rosager, Ann Mari; Sørensen, Mia D; Dahlrot, Rikke H

    2017-01-01

    /macrophage morphology. Neither FTH nor FTL increased with malignancy grade, but low FTH expression by both tumor cells (p = 0.03) and microglia/macrophages (p = 0.01) correlated with shorter survival in patients anaplastic astrocytoma. FTL-positive microglia/macrophages were frequent in glioblastomas, and high FTL...... levels correlated with shorter survival in the whole cohort (p = 0.01) and in patients with anaplastic astrocytoma (p = 0.02). Double-immunofluorescence showed that TfR1, FTH, and FTL were co-expressed to a limited extent with the stem cell-related marker CD133. FTH and FTL were also co-expressed by IBA...... in anaplastic astrocytomas, while high amounts of FTL-positive microglia/macrophages had a negative prognostic value. The results suggest that regulation of the iron metabolism in astrocytic brain tumors is complex involving both autocrine and paracrine signaling....

  11. Finding of IDH1 R132H mutation in histologically non-neoplastic glial tissue changes surgical strategies, a case report

    DEFF Research Database (Denmark)

    Søndergaard, Christian Baastrup; Scheie, David; Sehested, Astrid Marie

    2017-01-01

    INTRODUCTION: In 2016, the WHO classification of diffuse astrocytoma began to include isocitrate dehydrogenase (IDH) mutation in addition to histology. RESULTS: We here demonstrate a case where a 14-year-old boy presented with a parietal tumor with no histological evidence of neoplasia but with a......INTRODUCTION: In 2016, the WHO classification of diffuse astrocytoma began to include isocitrate dehydrogenase (IDH) mutation in addition to histology. RESULTS: We here demonstrate a case where a 14-year-old boy presented with a parietal tumor with no histological evidence of neoplasia...... but with an IDH1 mutation. Due to the IDH1 R132H mutation, the patient was diagnosed with diffuse astrocytoma WHO grade II and underwent successful gross total resection of this near-eloquently located tumor. CONCLUSION: This case exemplifies how inclusion of immunohistochemistry in tumor classification alters...

  12. Flavopiridol in Treating Children With Relapsed or Refractory Solid Tumors or Lymphomas

    Science.gov (United States)

    2013-07-01

    Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Liver Cancer; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Medulloblastoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Recurrent Retinoblastoma; Recurrent Wilms Tumor and Other Childhood Kidney Tumors; Recurrent/Refractory Childhood Hodgkin Lymphoma; Unspecified Childhood Solid Tumor, Protocol Specific

  13. Predicting the "usefulness" of 5-ALA-derived tumor fluorescence for fluorescence-guided resections in pediatric brain tumors

    DEFF Research Database (Denmark)

    Stummer, Walter; Rodrigues, Floriano; Schucht, Philippe

    2014-01-01

    . Fluorescence was found useful in 12 of 14 glioblastomas (85 %), four of five anaplastic astrocytomas (60 %), and eight of ten ependymomas grades II and III (80 %). Fluorescence was found inconsistently useful in PNETs (three of seven; 43 %), gangliogliomas (two of five; 40 %), medulloblastomas (two of eight......, 25 %) and pilocytic astrocytomas (two of 13; 15 %). RPA of pre-operative factors showed tumors with supratentorial location, strong contrast enhancement and first operation to have a likelihood of useful fluorescence of 64.3 %, as opposed to infratentorial tumors with first surgery (23...

  14. Stereological estimates of nuclear volume and other quantitative variables in supratentorial brain tumors. Practical technique and use in prognostic evaluation

    DEFF Research Database (Denmark)

    Sørensen, Flemming Brandt; Braendgaard, H; Chistiansen, A O

    1991-01-01

    the practical technique. The continuous variables were correlated with the subjective, qualitative WHO classification of brain tumors, and the prognostic value of the parameters was assessed. Well differentiated astrocytomas (n = 14) had smaller estimates of the volume-weighted mean nuclear volume and mean...... was significantly increased in glioblastomas (2p = 0.01). Three-dimensional, shape-independent estimates of macroscopical tumor volume were not different in anaplastic astrocytomas and glioblastomas (2p = 0.39). Histological type of tumor and mitotic index were of significant prognostic value (2p = 8.2.10(-6) and 2...... techniques in the prognostic evaluation of primary brain tumors....

  15. Supratentorial tumors; Supratentorielle Tumoren

    Energy Technology Data Exchange (ETDEWEB)

    Grunwald, I.; Dillmann, K.; Roth, C.; Backens, M.; Reith, W. [Universitaetsklinikum Saarland, Homburg (Germany). Klinik fuer Diagnostische und Interventionelle Neuroradiologie

    2007-06-15

    Magnetic resonance imaging is a routine diagnostic measure for a suspected intracerebral mass. Computed tomography is usually also indicated. Further diagnostic procedures as well as the interpretation of the findings vary depending on the tumor location. This contribution discusses the symptoms and diagnostics for supratentorial tumors separated in relation to their intra- or extracranial location. Supratentorial tumors include astrocytoma, differentiated by their circumscribed and diffuse growth, ganglioglioma, ependyoma, neurocytoma, primitive neuroectodermal tumors (PNET), oligodendroglioma, dysembryoplastic neuroepithelial tumors (DNET), meningoangiomatosis, pineal tumors, hamartoma, lymphoma, craniopharyngeoma and metastases. The supratentorial extracranial tumors include the choroid plexus, colloid cysts, meningeoma, infantile myofibromatosis and lipoma. The most common subforms, especially of astrocytoma, will also be presented. (orig.)

  16. Malignant glioma after bombshell injury.

    Science.gov (United States)

    Troost, D; Tulleken, C A

    1984-01-01

    A case of post-traumatic glioma is presented. The patient, wounded in the head in World War II by a bombshell, developed symptoms of an intracranial tumor in 1982. Histopathologically the tumor was an astrocytoma grade III. The tumor was in direct continuity with an old abscess membrane.

  17. D:\\African Health Sciences\\New

    African Journals Online (AJOL)

    user

    sions is reported to have improved following removal of a right frontal lobe mixed oligoastrocytoma or dysembryoplastic neuroepithelial tumour 5. A case is reported of a 19-year-old female who had undergone resection of an astrocytoma of the left basal temporal lobe which had initially presented with psy- chomotor and ...

  18. Untitled

    African Journals Online (AJOL)

    All patients with spinal tumors under— went lamineetomy only. Sixty five percent of those with intracranial tumors underwent craniotomy; 34% under— went stereotactic biopsy. The most common intracranial tumor was high—grade astrocytoma (HGA), 23%. The Ieft frontal lobe was the most common location of the intracra-.

  19. Author Details

    African Journals Online (AJOL)

    The Histological effects of microwave oven on bone decalcification using gooding and stewart fluid at varying temperatures and concentrations. Abstract PDF · Vol 1, No 4 (2012) - Articles The combined incidence of Grade II and Grade IV astrocytoma in the brain of rats fed with diet containing Yaji: A complex Nigerian Suya ...

  20. Boron neutron capture therapy (BNCT). Recent aspect, a change from thermal neutron to epithermal neutron beam and a new protocol

    Energy Technology Data Exchange (ETDEWEB)

    Nakagawa, Yoshinobu [Dept. of Neurosurgery National Kagawa Children' s Hospital, Zentsuji, Kagawa (Japan)

    1999-08-01

    Since 1968, One-hundred seventy three patients with glioblastoma (n=81), anaplastic astrocytoma (n=44), low grade astrocytoma (n=16) or other types of tumor (n=32) were treated by boron-neutron capture therapy (BNCT) using a combination of thermal neutron and BSH in 5 reactors (HTR n=13, JRR-3 n=1, MuITR n=98, KUR n=28, JRR-2 n=33). Out of 101 patients with glioma treated by BNCT under the recent protocol, 33 (10 glioblastoma, 14 anaplastic astrocytoma, 9 low grade astrocytoma) patients lived or have lived longer than 3 years. Nine of these 33 lived or have lived longer than 10 years. According to the retrospective analysis, the important factors related to the clinical results were tumor dose radiation dose and maximum radiation dose in thermal brain cortex. The result was not satisfied as it was expected. Then, we decided to introduce mixed beams which contain thermal neutron and epithermal neutron beams. KUR was reconstructed in 1996 and developed to be available to use mixed beams. Following the shutdown of the JRR-2, JRR-4 was renewed for medical use in 1998. Both reactors have capacity to yield thermal neutron beam, epithermal neutron beam and mixed beams. The development of the neutron source lead us to make a new protocol. (author)

  1. Drug: D08891 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available PPREDLR (Disulfide bridge: 32-60; 48-74; 136-158) Peptide Treatment of malignant glioma, including gliobla...stoma multiforme and anaplastic astrocytoma interleukin 13 (IL13) [HSA:3596] [KO:K05435] analogue CAS: 372075-36-0 PubChem: 96025574 ...

  2. The prevalence of cervical ribs in Enugu, Nigeria

    African Journals Online (AJOL)

    2015-11-18

    Nov 18, 2015 ... cancer patients, especially acute lymphoblastic leukemia, astrocytoma, and germ cell tumors.[6,11,12] In cases of suspected child abuse, cervical rib presence may be mistaken for fracture of the first rib.[1]. The majority of patients with cervical ribs are asymptomatic and in patients requiring operation for ...

  3. Author Details

    African Journals Online (AJOL)

    Zewdie, Kibruyisfaw. Vol 21, No 3 (2016) - Articles Cerebellar Pilomyxoid Astrocytoma Abstract PDF. ISSN: 2073-9990. AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors · FAQ's · More about AJOL · AJOL's Partners · Terms and Conditions of Use · Contact AJOL · News. OTHER ...

  4. Enhancing predicted efficacy of tumor treating fields therapy of glioblastoma using targeted surgical craniectomy: A computer modeling study

    DEFF Research Database (Denmark)

    Korshoej, Anders Rosendal; Saturnino, Guilherme Bicalho; Rasmussen, Line Kirkegaard

    2016-01-01

    with deeply seated right thalamic anaplastic astrocytoma. Field strength was assessed in the tumor regions before and after virtual removal of bone areas of varying shape and size (10 to 100 mm) immediately above the tumor. Field strength was evaluated before and after tumor resection to assess realistic...

  5. Author Details

    African Journals Online (AJOL)

    Ujaddughe, MO. Vol 1, No 4 (2012) - Articles The combined incidence of Grade II and Grade IV astrocytoma in the brain of rats fed with diet containing Yaji: A complex Nigerian Suya meat sauce. Abstract PDF · Vol 3, No 3 (2014) - Articles Liver weight changes in wistar rats treated with crude aqueous extracts of Mangifera ...

  6. Regional cerebral blood flow in various types of brain tumor. Effect of the space-occupying lesion on blood flow in brain tissue close to and remote from tumor site

    DEFF Research Database (Denmark)

    Kuroda, K; Skyhøj Olsen, T; Lassen, N A

    1982-01-01

    Regional cerebral blood flow (rCBF) was measured in 23 patients with brain tumors using the 133Xe intra-carotid injection method and a 254 channel gamma camera. The glioblastomas (4) and astrocytomas (4) all showed hyperemia in the tumor and tumor-near region. This was also seen in several...

  7. Characteristic and surgical results of multisegment intramedullary cervical spinal cord tumors

    Directory of Open Access Journals (Sweden)

    Jian-jun Sun, M.D.

    2017-03-01

    Conclusion: This series of MSICCT showed that high extent of surgical resection could be achieved in most ependymomas with good long-term outcome. Astrocytomas, in contrary remained challenging with 25% achieved gross total resection. Overall, compared to previous surgical series, we showed encouraging improvement in the clinical outcome of these patients managed surgically.

  8. Author Details

    African Journals Online (AJOL)

    Obwolo, M J. Vol 28, No 1 (1997) - Articles Original Papers Ostertagia ostertagi infection in cattle on an irrigated farm on the highveld of Zimbabwe Abstract · Vol 28, No 2 (1997) - Articles Undifferentiated astrocytoma in a Doberman Pinscher bitch. Abstract · Vol 28, No 3 (1997) - Articles Spinal malacia, abscess and ...

  9. Kynurenic acid synthesis by human glioma

    DEFF Research Database (Denmark)

    Vezzani, A; Gramsbergen, J B; Versari, P

    1990-01-01

    , 200 or 1000 microM L-kynurenine, the immediate bioprecursor of KYNA, freshly prepared tissue slices in a dose-dependent fashion produced KYNA which was detected in the incubation medium. De novo synthesized KYNA was identified by several chromatographic procedures. Astrocytomas produced significantly...

  10. Transient mutism after anterior transcallosal approach | Naama ...

    African Journals Online (AJOL)

    Postoperative mutism is an infrequent complication of brain surgery. We report a third ventricular astrocytoma in a 16-year-old boy. The tumor was totally removed via anterior transcallosal approach. The operation was uneventful. On the second postoperative day he became mute. He could follow verbal commands, and ...

  11. Author Details

    African Journals Online (AJOL)

    Murondoti, A. Vol 28, No 2 (1997) - Articles Undifferentiated astrocytoma in a Doberman Pinscher bitch. Abstract · Vol 31, No 3 (2000) - Articles Syndactylysim in a Mashona calf: A case report. Abstract. ISSN: 1016-1511. AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors · FAQ's ...

  12. Author Details

    African Journals Online (AJOL)

    Samkange, A. Vol 28, No 2 (1997) - Articles Undifferentiated astrocytoma in a Doberman Pinscher bitch. Abstract. ISSN: 1016-1511. AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors · FAQ's · More about AJOL · AJOL's Partners · Terms and Conditions of Use · Contact AJOL ...

  13. Author Details

    African Journals Online (AJOL)

    Abstract PDF · Vol 1, No 3 (2012) - Articles The effect of L-arginine on contralateral testes following 7200 Torsion - Detorsion of the Ipsilateral testes. Abstract PDF · Vol 1, No 4 (2012) - Articles The combined incidence of Grade II and Grade IV astrocytoma in the brain of rats fed with diet containing Yaji: A complex Nigerian ...

  14. Low expression of tissue inhibitor of metalloproteinases-1 (TIMP-1) in glioblastoma predicts longer patient survival

    DEFF Research Database (Denmark)

    Aaberg-Jessen, Charlotte; Christensen, Karina; Offenberg, Hanne Kjær

    2009-01-01

    but whether TIMP-1 is a prognostic marker in gliomas has not previously been investigated. In the present study, the TIMP-1 expression was investigated immunohistochemically in 112 formalin-fixed paraffin embedded astrocytomas and related to tumour grade and overall patient survival by scoring the TIMP-1...

  15. Author Details

    African Journals Online (AJOL)

    Trogrlić, Ivo. Vol 13, No 6 (2016) - Articles Treatment of progression of diffuse astrocytoma by herbal medicine: case report. Abstract PDF. ISSN: 0189-6016. AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors · FAQ's · More about AJOL · AJOL's Partners · Terms and Conditions of ...

  16. Cholecystokinin expression in tumors

    DEFF Research Database (Denmark)

    Rehfeld, Jens F

    2016-01-01

    in different neuroendocrine tumors; cerebral gliomas and astrocytomas and specific pediatric tumors. Tumor hypersecretion of CCK was recently reported in a patient with a metastatic islet cell tumor and hypercholecystokininemia resulting in a novel tumor syndrome, the cholecystokininoma syndrome. This review...

  17. Nogo-A expression in glial CNS tumors - A tool to differentiate between oligodendrogliomas and other gliomas?

    NARCIS (Netherlands)

    Kuhlmann, Tanja; Gutenberg, Angelika; Schulten, Hans-Juergen; Paulus, Werner; Rohde, Veit; Bruck, Wolfgang

    2008-01-01

    Gliomas are the most frequent primary brain tumors. In a minority of cases, the differentiation between astrocytomas and oligodendrogliomas based on morphologic characteristics alone can be difficult; though it is important, as patients with ohgodendrogliomas follow a more favorable clinical course.

  18. ISSN 2073-9990 East Cent. Afr. J. surg

    African Journals Online (AJOL)

    Hp 630 Dual Core

    when only a subtotal resection is achieved.1 These highly treatable and potentially curable pediatric tumors are ... Earlier reports pointed out unusual features of some pediatric astrocytomas, particularly ... to neurosurgical referral clinics at which time he presented with global headache,projectile vomiting of ingested matter ...

  19. POSTERIOR CRANIAL FOSSA TUMOURS IN CHILDREN AT ...

    African Journals Online (AJOL)

    hi-tech

    2004-05-05

    May 5, 2004 ... symptoms were the most common mode of presentation (30%) followed by headaches and vomiting. Twenty percent of our patients ... paediatric posterior fossa tumours are medulloblastoma. (20%) astrocytoma (15%) ... cranial nerve palsies, headaches, vomiting and blindness due to raised intracranial ...

  20. Role of proton magnetic resonance spectroscopy in diagnosis of ...

    African Journals Online (AJOL)

    Mohammed Mahmoud Donia

    2012-01-23

    Jan 23, 2012 ... pediatric patients with pilocytic astrocytomas because of its ability to provide anatomical detail. ... Subjects and methods: This study included seven pediatric patients with histopathologically proven ..... Case (4): A 15-year-old male patient presented by headache and disturbed level of consciousness.

  1. Static and dynamic18F-FET PET for the characterization of gliomas defined by IDH and 1p/19q status.

    Science.gov (United States)

    Verger, Antoine; Stoffels, Gabriele; Bauer, Elena K; Lohmann, Philipp; Blau, Tobias; Fink, Gereon R; Neumaier, Bernd; Shah, Nadim J; Langen, Karl-Josef; Galldiks, Norbert

    2018-03-01

    The molecular features isocitrate dehydrogenase (IDH) mutation and 1p/19q co-deletion have gained major importance for both glioma typing and prognosis and have, therefore, been integrated in the World Health Organization (WHO) classification in 2016. The aim of this study was to characterize static and dynamic O-(2- 18 F-fluoroethyl)-L-tyrosine ( 18 F-FET) PET parameters in gliomas with or without IDH mutation or 1p/19q co-deletion. Ninety patients with newly diagnosed and untreated gliomas with a static and dynamic 18 F-FET PET scan prior to evaluation of tumor tissue according to the 2016 WHO classification were identified retrospectively. Mean and maximum tumor-to-brain ratios (TBR mean/max ), as well as dynamic parameters (time-to-peak and slope) of 18 F-FET uptake were calculated. Sixteen (18%) oligodendrogliomas (IDH mutated, 1p/19q co-deleted), 27 (30%) astrocytomas (IDH mutated only), and 47 (52%) glioblastomas (IDH wild type only) were identified. TBR mean , TBR max , TTP and slope discriminated between IDH mutated astrocytomas and IDH wild type glioblastomas (P IDH mutated, 1p/19q co-deleted) and glioblastomas or astrocytomas. Furthermore, TBR mean , TBR max , TTP, and slope discriminated between gliomas with and without IDH mutation (p IDH mutation status. However, IDH mutated and 1p/19q co-deleted oligodendrogliomas cannot be differentiated from glioblastomas and astrocytomas by 18 F-FET PET.

  2. Gliomatosis cerebri--an appropriate diagnosis? Case reports

    DEFF Research Database (Denmark)

    Fallentin, E; Skriver, E; Herning, Gudrun Margrethe

    1997-01-01

    PURPOSE: To evaluate the premises for the diagnosis gliomatosis cerebri in relation to diffuse astrocytomas. MATERIAL AND METHODS: CT, MR images and pathological analyses were used to assess the cases of 4 patients with diffusely infiltrating astrocytic tumours that radiologically, clinically and...

  3. Cellular Consequences of Telomere Shortening in Histologically Normal Breast Tissues

    Science.gov (United States)

    2011-09-01

    mechanism. Cytogenet Genome Res 2008, 122:281–291 12. Cesare AJ, Reddel RR: Alternative lengthening of telomeres: models, mechanisms and implications......astrocytomas. Clin. Cancer Res. 11, 217 (2005). Medline 21. M. A. Cerone, C. Autexier, J. A. Londoño- Vallejo , S. Bacchetti, A human cell line that maintains

  4. Download this PDF file

    African Journals Online (AJOL)

    2001-03-03

    Mar 3, 2001 ... neurone palsy of the VII nerve and sensori—neural deafness were recorded in the two patients with acoustic neuromas. Cerebellar ataxia was recorded in one patient suspected of having had a cerebellar astrocytoma. Metastatic lesions to the brain and skull manifested as multiple cranial masses.

  5. Neurology; Neurologie

    Energy Technology Data Exchange (ETDEWEB)

    Schlienger, M.; Nataf, F.; Foulquier, J.N.; Gres, B.; Keraudy, K.; Orthuon, A.; Huguet, F.; Ghossoub, M.; Roux, F.X.; Touboul, E.; El Morjani, T.; Mharrech, A.; Benchakroun, N.; Jouhadi, H.; Tawfiq, N.; Sahraoui, S.; Benider, A.; Berges, O.; Abrous, S.; Lang, P.; Toubiana, T.; Ontkova, M.; Boustany, R.; Lopez, S.; Brun, B.; Mazeron, J.J.; Simon, J.M.; Toledano, I.; Khalil, T.; Gilliot, O.; Durando, X.; Bay, J.O.; Tortochaux, J.; Bourry, N.; Kemeny, J.L.; Lapeyre, M.; Verrelle, P.; Malkoun-Mongenot, N.; Greve, E.; Schmitt, T.; Mazloum, W.; Mazzola, L.; Duthel, R.; Brunon, J.; Sunyach, M.S.; Ghesquiere, H.G.; Carrie, C.C.; Blay, J.Y

    2007-11-15

    7 articles concern cerebral metastases, medulloblastomas, glioblastomas,astrocytomas, cerebral lymphomas and study the different therapies between radiotherapy and chemotherapy, concomitant or adjuvant with different drugs as carbo-platin, etoposide, temozolomid, methotrexate. Tolerance and toxicity are noticed. (N.C.)

  6. Type and frequency of IDH1 and IDH2 mutations are related to astrocytic and oligodendroglial differentiation and age: a study of 1,010 diffuse gliomas.

    NARCIS (Netherlands)

    Hartmann, C.; Meyer, J.; Balss, J.; Capper, D.; Mueller, W.; Christians, A.; Felsberg, J.; Wolter, M.; Mawrin, C.; Wick, W.; Weller, M.; Herold-Mende, C.; Unterberg, A.; Jeuken, J.W.M.; Wesseling, P.; Reifenberger, G.; Deimling, A. Von

    2009-01-01

    Somatic mutations in the IDH1 gene encoding cytosolic NADP+-dependent isocitrate dehydrogenase have been shown in the majority of astrocytomas, oligodendrogliomas and oligoastrocytomas of WHO grades II and III. IDH2 encoding mitochondrial NADP+-dependent isocitrate dehydrogenase is also mutated in

  7. The pathogenesis of cysts accompanying intra-axial primary and metastatic tumors of the central nervous system

    NARCIS (Netherlands)

    Lohle, PNM; Wurzer, HAL; Seelen, PJ; Kingma, LM; Go, KG

    1998-01-01

    Recent reports have suggested that cyst formation accompanying astrocytomas in the central nervous system (CNS) is due to an edematous process caused by blood-brain barrier (BBB) disruption and not a result of necrosis. This study is performed to investigate whether the hypothesis of cyst formation

  8. Correlations between in vivo (1)H MRS and ex vivo (1)H HRMAS metabolite measurements in adult human gliomas.

    NARCIS (Netherlands)

    Opstad, K.S.; Wright, A.J.; Bell, B.A.; Griffiths, J.R.; Howe, F.A.

    2010-01-01

    PURPOSE: To assess how accurately ex vivo high-resolution magic angle spinning (HRMAS) proton magnetic resonance spectroscopy ((1)H MRS) from small biopsy tissues relate to in vivo (1)H MRS (from larger tumor volumes) in human astrocytomas. MATERIALS AND METHODS: In vivo (PRESS, TE = 30 msec) and ex

  9. Characterization of Cancer Stem Cells in Patients with Brain ...

    African Journals Online (AJOL)

    Background: Gliomas, in general, and astrocytomas, in particular, represent the most frequent primary brain tumors. Nowadays, it is increasingly believed that gliomas may arise from cancer stem cells, which share several characteristics with normal neural stem cells. Brain tumor stem cells have been found to express a ...

  10. African Journal of Neurological Sciences - 2009 Vol. 28 No 1

    African Journals Online (AJOL)

    RESUME. Postoperative mutism is an infrequent complication of brain surgery. We report a third ventricular astrocytoma in a 16-year-old boy. The tumor was totally removed via anterior transcallosal approach. The operation was uneventful. On the second postoperative day he became mute. He could follow verbal.

  11. GFAP isoforms control intermediate filament network dynamics, cell morphology, and focal adhesions

    NARCIS (Netherlands)

    Moeton, M.; Stassen, O.M.J.A.; Sluijs, J.A.; van der Meer, V.W.N.; Kluivers, L.J.; van Hoorn, H.; Schmidt, T.; Reits, E.A.J.; van Strien, M.E.; Hol, E.M.

    2016-01-01

    Glial fibrillary acidic protein (GFAP) is the characteristic intermediate filament (IF) protein in astrocytes. Expression of its main isoforms, GFAPα and GFAPδ, varies in astrocytes and astrocytoma implying a potential regulatory role in astrocyte physiology and pathology. An IF-network is a dynamic

  12. INTRACRANIAL NEOPLASMS IN IBADAN, NIGERIA B.J. OLASODE ...

    African Journals Online (AJOL)

    hi-tech

    2000-01-01

    Jan 1, 2000 ... One hundred and thirty five neoplasms occurred in adults and 75 in children. There was no gender difference, the ratio being 1:1. Gliomas accounted for the largest group of tumours followed by metastases to the brain. Of the gliomas, astrocytoma was the commonest. Craniopharyngiomas were found to be.

  13. Intracranial neoplasmin Ibadan, Nigeria | Olasode | East African ...

    African Journals Online (AJOL)

    There was no gender difference, the ratio being 1:1. Gliomas accounted for the largest group of tumours followed by metastases to the brain. Of the gliomas, astrocytoma was the commonest. Craniopharyngiomas were found to becommon in children. Germ cell tumours were found to be uncommon. Conclusion: Gliomas are ...

  14. Characterization of Cancer Stem Cells in Patients with Brain ...

    African Journals Online (AJOL)

    ... 26-70 years) who were operated for brain astrocytomas. Immunohistochemical staining for Nestin, TP53, and Ki 67 was carried out on paraffin embedded tissue samples from the resected gliomas. Scores for markers' expression were statistically correlated with patients' age and gender, tumor grade, and patients' survival ...

  15. Astrocitoma de grado I en glándula pineal

    OpenAIRE

    Iglesias Rozas, José Rafael, 1942-

    1985-01-01

    Tres imágenes de un astrocitoma de grado I situado en la glándula pineal de un paciente de 10 años. Three pictures of a grade I astrocytoma located in the pineal gland of a 10-year-old male patient.

  16. Immunoblot analysis of the placental form of glutathione S-transferase in protein extracted from paraffin-embedded human glioma tissue.

    Science.gov (United States)

    Hara, A; Sakai, N; Yamada, H; Yoshimi, N; Tanaka, T; Mori, H

    1993-01-01

    Protein extracted from conventional formalin-fixed and paraffin-embedded tissue sections of human gliomas was examined for immunoblot analysis using antibody against the placental form of glutathione S-transferase (GST-pi). Four benign astrocytomas, five anaplastic astrocytomas and four glioblastomas were used in this study. The preliminary study demonstrated that immunoreactivity of GST-pi was well preserved in normal brain tissue and normal term placenta fixed in acetone, formalin or buffered formalin (pH 7.4). GST-pi in gliomas fixed in formalin also had a good immunoreactivity and showed clear bands on nitrocellulose membranes processed by the method of Western blotting using anti-GST-pi antibody. The results of immunoblot analysis for GST-pi indicate that the intensity of immunoreactivity of benign astrocytoma, anaplastic astrocytoma and glioblastoma increases with the advance of malignancy of these neoplasms. Western blot analysis for GST-pi can be performed using protein extracted from formalin-fixed and paraffin-embedded tissue sections, and the immunoreactive bands can be analyzed quantitatively by densitometric scanning.

  17. Separation and isolation of tautomers of 2-hydroxy-4 ...

    Indian Academy of Sciences (India)

    and absorption band at 406 nm. Compounds 3 and 4 were screened for selective antiproliferative activity in three cancer cell lines of different tissue types (COLO 205 (human colorectal adenocarcinoma), U87 MG (glioblastoma astrocytoma) and MIAPaCa-2 (human pancreatic carcinoma). Geometry-optimized structures for ...

  18. Central nervous system tumors: Radiologic pathologic correlation and diagnostic approach

    Directory of Open Access Journals (Sweden)

    Ishita Pant

    2015-01-01

    Full Text Available Objective: This study was conducted to formulate location-wise radiologic diagnostic algorithms and assess their concordance with the final histopathological diagnosis so as to evaluate their utility in a rural setting where only basic facilities are available. Materials and Methods: A retrospective analysis to assess the concordance of radiology (primarily MRI with final histopathology report was done. Based on the most common incidence of tumor location and basic radiology findings, diagnostic algorithms were prepared. Results: For supratentorial intraaxial parenchymal location concordance was seen in all high-grade astrocytomas, low- and high-grade oligodendrogliomas, metastatic tumors, primitive neuroectodermal tumors, high-grade ependymomas, neuronal and mixed neuro-glial tumors and tumors of hematopoietic system. Lowest concordance was seen in low-grade astrocytomas. In the supratentorial intraaxial ventricular location, agreement was observed in choroid plexus tumors, ependymomas, low-grade astrocytomas and meningiomas; in the supratentorial extraaxial location, except for the lack of concordance in the only case of metastatic tumor, concordance was observed in meningeal tumors, tumors of the sellar region, tumors of cranial and paraspinal nerves; the infratentorial intraaxial parenchymal location showed agreement in low- as well as high-grade astrocytomas, metastatic tumors, high-grade ependymoma, embryonal tumors and hematopoietic tumors; in the infratentorial intraaxial ventricular location, except for the lack of concordance in one case of low-grade astrocytoma and two cases of medulloblastomas, agreement was observed in low- and high-grade ependymoma; infratentorial extraaxial tumors showed complete agreement in all tumors of cranial and paraspinal nerves, meningiomas, and hematopoietic tumors. Conclusion: A location-based approach to central nervous system (CNS tumors is helpful in establishing an appropriate differential diagnosis.

  19. Potential Role of Methylation Marker in Glioma Supporting Clinical Decisions

    Directory of Open Access Journals (Sweden)

    Krzysztof Roszkowski

    2016-11-01

    Full Text Available The IDH1/2 gene mutations, ATRX loss/mutation, 1p/19q status, and MGMT promoter methylation are increasingly used as prognostic or predictive biomarkers of gliomas. However, the effect of their combination on radiation therapy outcome is discussable. Previously, we demonstrated that the IDH1 c.G395A; p.R132H mutation was associated with longer survival in grade II astrocytoma and GBM (Glioblastoma. Here we analyzed the MGMT promoter methylation status in patients with a known mutation status in codon 132 of IDH1, followed by clinical and genetic data analysis based on the two statuses. After a subtotal tumor resection, the patients were treated using IMRT (Intensity-Modulated Radiation Therapy with 6 MeV photons. The total dose was: 54 Gy for astrocytoma II, 60 Gy for astrocytoma III, 60 Gy for glioblastoma, 2 Gy per day, with 24 h intervals, five days per week. The patients with MGMT promoter methylation and IDH1 somatic mutation (OS = 40 months had a better prognosis than those with MGMT methylation alone (OS = 18 months. In patients with astrocytoma anaplasticum (n = 7 with the IDH1 p.R132H mutation and hypermethylated MGMT, the prognosis was particularly favorable (median OS = 47 months. In patients with astrocytoma II meeting the above criteria, the prognosis was also better than in those not meeting those criteria. The IDH1 mutation appears more relevant for the prognosis than MGMT methylation. The IDH1 p.R132H mutation combined with MGMT hypermethylation seems to be the most advantageous for treatment success. Patients not meeting those criteria may require more aggressive treatments.

  20. ADAR2-editing activity inhibits glioblastoma growth through the modulation of the CDC14B/Skp2/p21/p27 axis.

    Science.gov (United States)

    Galeano, F; Rossetti, C; Tomaselli, S; Cifaldi, L; Lezzerini, M; Pezzullo, M; Boldrini, R; Massimi, L; Di Rocco, C M; Locatelli, F; Gallo, A

    2013-02-21

    Grade IV astrocytoma or glioblastoma multiforme (GBM) is one of the most aggressive and lethal tumors affecting humans. ADAR2-mediated A-to-I RNA editing, an essential post-transcriptional modification event in brain, is impaired in GBMs and astrocytoma cell lines. However, the role of ADAR2 editing in astrocytomas remains to be defined. Here, we show that ADAR2 editing rescue in astrocytomas prevents tumor growth in vivo and modulates an important cell cycle pathway involving the Skp2/p21/p27 proteins, often altered in glioblastoma. We demonstrate that ADAR2 deaminase activity is essential to inhibit tumor growth. Indeed, we identify the phosphatase CDC14B, which acts upstream of the Skp2/p21/p27 pathway, as a novel and critical ADAR2 target gene involved in glioblastoma growth. Specifically, ADAR2-mediated editing on CDC14B pre-mRNA increases its expression with a consequent reduction of the Skp2 target protein, as shown both in vitro and in vivo. We found that, compared to normal brain, both CDC14B editing and expression are progressively impaired in astrocytomas from grade I to IV, being very low in GBMs. These findings (1) demonstrate that post-transcriptional A-to-I RNA editing might be crucial for glioblastoma pathogenesis, (2) identify ADAR2-editing enzyme as a novel candidate tumor suppressor gene and (3) provide proof of principle that ADAR2 or its substrates may represent a suitable target(s) for possible novel, more effective and less toxic approaches to the treatment of GBMs.

  1. Surgical management of tumors producing the thalamopeduncular syndrome of childhood.

    Science.gov (United States)

    Broadway, S Jared; Ogg, Robert J; Scoggins, Matthew A; Sanford, Robert; Patay, Zoltan; Boop, Frederick A

    2011-06-01

    Thalamopeduncular tumors arise at the junction of the inferior thalamus and cerebral peduncle and present with a common clinical syndrome of progressive spastic hemiparesis. Pathologically, these lesions are usually juvenile pilocytic astrocytomas and are best treated with resection with the intent to cure. The goals of this study are to define a common clinical syndrome produced by thalamopeduncular tumors and to discuss imaging characteristics as well as surgical adjuncts, intraoperative nuances, and postoperative complications relating to the resection of these neoplasms. The authors present a retrospective review of their experience with 10 children presenting between 3 and 15 years of age with a thalamopeduncular syndrome. Formal preoperative MR imaging was obtained in all patients, and diffusion tensor (DT) imaging was performed in 9 patients. Postoperative MR imaging was obtained to evaluate the extent of tumor resection. A prospective analysis of clinical outcomes was then conducted by the senior author. Pilocytic astrocytoma was the pathological diagnosis in 9 cases, and the other was fibrillary astrocytoma. Seven of 9 pilocytic astrocytomas were completely resected. Radical surgery was avoided in 1 child after DT imaging revealed that the corticospinal tract (CST) coursed through the center of the tumor, consistent with the infiltrative nature of fibrillary astrocytoma as identified by stereotactic biopsy. In 8 patients, tractography served as an important adjunct for designing a surgical approach that spared the CST. In 6 cases the CSTs were pushed anterolaterally, making a transsylvian approach a poor choice, as was evidenced by the first patient in the series, who underwent operation prior to the advent of tractography, and who awoke with a dense contralateral hemiparesis. Thus, subsequent patients with this deviation pattern underwent a transcortical approach via the middle temporal gyrus. One patient exhibited medial deviation of the tracts and

  2. Glioblastoma multiforme in a child with tuberous sclerosis complex.

    Science.gov (United States)

    Vignoli, Aglaia; Lesma, Elena; Alfano, Rosa Maria; Peron, Angela; Scornavacca, Giulia Federica; Massimino, Maura; Schiavello, Elisabetta; Ancona, Silvia; Cerati, Michele; Bulfamante, Gaetano; Gorio, Alfredo; Canevini, Maria Paola

    2015-10-01

    Tuberous Sclerosis Complex (TSC) is characterized by the presence of benign tumors in the brain, kidneys, heart, eyes, lungs, and skin. The typical brain lesions are cortical tubers, subependimal nodules and subependymal giant-cell astrocytomas. The occurrence of malignant astrocytomas such as glioblastoma is rare. We report on a child with a clinical diagnosis of TSC and a rapidly evolving glioblastoma multiforme. Genetic analysis identified a de novo mutation in TSC2. Molecular characterization of the tumor was performed and discussed, as well as a review of the literature where cases of TSC and glioblastoma multiforme are described. Although the co-occurrence of TSC and glioblastoma multiforme seems to be rare, this possible association should be kept in mind, and proper clinical and radiological follow up should be recommended in these patients. © 2015 Wiley Periodicals, Inc.

  3. Rapid progression of gliomatosis cerebri to secondary glioblastoma, factors that affects the progression rate: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hee Kyung; Yu, In Kyu; Kim, Seung Min; Kim, Joo Heon; Lee, Seung Hoon; Lee, Seung Yeon [Eulji University Hospital, Daejeon (Korea, Republic of)

    2017-03-15

    Glioblastomas may develop de novo or through progression from low-grade or anaplastic astrocytomas. The term 'primary glioblastoma' refers to a glioblastoma that lacks a precursor lesion and has a clinical history of less than three months. On the other hand, the term 'secondary glioblastoma' indicates that the glioblastoma has progressed from a low-grade tumor after a long latency period and often manifests in younger patients. These subtypes of glioblastoma develop via different genetic pathways, and they differ in prognosis and response to therapy. Thus, differential diagnosis of these subtypes and prediction of the factors that affect the progression from low-grade diffuse astrocytoma to secondary glioblastoma would be clinically very important. We present a rare case of secondary glioblastoma, which developed only three months after the follow up imaging evaluations, with a history of low grade glioma, and present the factors that cause rapid progression.

  4. Application of NMR tomography to diagnosis of cerebral diseases. Results of two years experience

    Energy Technology Data Exchange (ETDEWEB)

    Fiegler, W.; Schoerner, W.; Felix, R.

    1987-01-05

    The current paper demonstrates our experience of 1200 examinations of the brain, using magnetic resonance tomography (MRT). The MRT-characteristics of oedema haemorrhage, fatty tumors, calcifications, demyelinisation and tumors are described. A significant advantage of MRT is its excellent contrast resolution of soft tissues, this results in better demonstration of corticomedullary contrast, areas of demyelinization, astrocytomas and gliosis. Demonstration of lesions near the skull base and the middle and posterior fossa is improved with magnetic resonance tomography by the ability of obtaining coronal and sagittal images and by the absence of artefacts due to bone. MRT is especially indicated in patients with tumors (astrocytomas, midline lesions, tumors of the posterior fossa) temporal lobe epilepsy and multiple sclerosis.

  5. DIFFERENTIATION OF RETINAL ASTROCYTIC HAMARTOMA FROM OTHER RETINAL NEOPLASMS: A CASE REPORT

    Directory of Open Access Journals (Sweden)

    A. S. Olshanskaya

    2017-01-01

    Full Text Available Astrocytic retinal hamartoma (phacoma, astrocytoma is a benign tumor, formed through proliferation of glial astrocytes and blood vessels of the sensory part of the retina. For the first time, eye involvement in tuberous sclerosis (TS was described by J. van der Hoeva, Dutch ophthalmologist in 1921. A characteristic glial tumor is still considered a classic manifestation of this disease, however, retinal astrocytoma can be observed in practically healthy young people or children. We present the case of a 19-year-old woman diagnosed with multiple retinal hamartomas in the right eye. In addition to ophthalmoscopy, we used the additional diagnostic methods to determine the form of hamartomas (calcined or uncalcined and differentiate astrocytic retinal hamartoma from other tumors of the retina and choroid as well as to exclude pathological changes in the central nervous system. 

  6. Intracranial Demyelinating Pseudotumor: A Case Report and Review of the Literature.

    Science.gov (United States)

    Ning, Xianbin; Zhao, Changfu; Wang, Caiqin; Zhang, Duo; Luo, Qi

    2017-01-01

    Demyelinating pseudotumor is a rare inflammatory demyelinating disease of the central nervous system (CNS) that has a similar clinical presentation and computed tomography (CT) and magnetic resonance imaging (MRI) imaging findings as brain tumors or abscesses. Unlike brain tumors, demyelinating pseudotumors respond well to steroid hormones. There are only a few reported cases of intracranial demyelinating pseudotumors in the literature. In this case report, we present the diagnosis and treatment of demyelinating pseudotumor in a patient whose condition was initially misdiagnosed as an astrocytoma. Based on the literature and our case, we formulated an outline for the differential diagnosis of demyelinating pseudotumor and astrocytoma. A timely and correct diagnosis of demyelinating pseudotumor would avoid blind surgery, radiotherapy and chemotherapy, which are used to treat brain tumors.

  7. EGFR intragenic loss and gene amplification in astrocytic gliomas.

    Science.gov (United States)

    Arjona, Dolores; Bello, M Josefa; Rey, Juan A

    2006-01-01

    We have studied EGFR gene amplification and allelic status of chromosome 7 in 68 tumors consisting of 34 WHO grade IV glioblastomas (26 primary and 8 secondary), 14 WHO grade III anaplastic astrocytomas, and 20 WHO grade II astrocytomas, by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP), quantitative PCR, and microsatellite analysis. EGFR gene amplification was present in 27 of these tumors (40%), and we identified allelic losses at 7p11 approximately p14 in 38 of the 68 cases (56%), including 17 tumors displaying loss for EGFR intragenic markers. The positive correlation (P < 0.05, chi(2)) between tumors with EGFR intragenic loss and EGFR gene amplification, frequently displaying the EGFR vIII form, suggests that EGFR gene rearrangement leading to intragenic loss is a molecular event that participates in the amplification process of this gene.

  8. Rare mutations of the DMBT1 gene in human astrocytic gliomas

    DEFF Research Database (Denmark)

    Mueller, Wolf; Mollenhauer, Jan; Stockhammer, Florian

    2002-01-01

    The Deleted in Malignant Brain Tumors 1 gene (DMBT1) has been proposed as a tumor suppressor gene candidate in human brain tumors, based on the observation of homozygous deletions affecting the DMBT1 region or part of the gene. In order to support this hypothesis, we performed a mutational analysis...... of the entire coding region of DMBT1, employing SSCP analysis and direct DNA sequencing in a series of 79 astrocytic gliomas. Five somatic mutations were detected. Two mutations, one of which resulted in an amino acid exchange, occurred in glioblastomas. One pilocytic astrocytoma carried two missense mutations...... and another pilocytic astrocytoma contained a somatic mutation, not affecting the presumed protein. In addition, 21 of the 27 single nucleotide polymorphisms identified in this study have not been recognized previously. The data indicate, that small mutations are not a frequent finding in gliomas....

  9. Research progress of IDH1 and IDH2 mutations in gliomas

    Directory of Open Access Journals (Sweden)

    Shan-shan ZHANG

    2015-11-01

    Full Text Available The gene mutations of isocitrate dehydrogenase 1 and 2 (IDH1/2 mainly occur in astrocytoma, anaplastic astrocytoma, oligodendroglioma, anaplastic oligodendroglioma, oligoastrocytoma, anaplastic oligoastrocytoma and secondary glioblastoma. The IDH1/2 gene mutation can alter proteinase function, consume α-ketoglutarate and nicotinamide adenine dinucleotide phosphate-reduced (NADPH and thus produce carcinogenic metabolite, 2-hydroxyglutarate. The intracellular accumulation of 2-hydroxyglutarate will induce a series of downstream effects which may result in the development of gliomas mentioned above. Both IDH1/2 mutations and other concomitant hereditary variations are biomarkers for differential diagnosis and IDH1/2 mutations are also independent factors for the prognosis of gliomas. The molecular targeting therapy for IDH1/2 mutations has become the research focus of glioma treatment. This review summarizes the recent progress of this field. DOI: 10.3969/j.issn.1672-6731.2015.11.017

  10. Quantitation of glial fibrillary acidic protein in human brain tumours

    DEFF Research Database (Denmark)

    Rasmussen, S; Bock, E; Warecka, K

    1980-01-01

    The glial fibrillary acidic protein (GFA) content of 58 human brain tumours was determined by quantitative immunoelectrophoresis, using monospecific antibody against GFA. Astrocytomas, glioblastomas, oligodendrogliomas, spongioblastomas, ependymomas and medulloblastomas contained relatively high...... amounts of GFA, up to 85 times the concentration in parietal grey substance of normal human brain. GFA was not found in neurinomas, meningiomas, adenomas of the hypophysis, or in a single case of metastasis of adenocarcinoma. Non-glial tumours of craniopharyngioma and haemangioblastoma were infiltrated...

  11. Diffusion kurtosis imaging of gliomas grades II and III - a study of perilesional tumor infiltration, tumor grades and subtypes at clinical presentation

    Directory of Open Access Journals (Sweden)

    Delgado Anna F.

    2017-05-01

    Full Text Available Diffusion kurtosis imaging (DKI allows for assessment of diffusion influenced by microcellular structures. We analyzed DKI in suspected low-grade gliomas prior to histopathological diagnosis. The aim was to investigate if diffusion parameters in the perilesional normal-appearing white matter (NAWM differed from contralesional white matter, and to investigate differences between glioma malignancy grades II and III and glioma subtypes (astrocytomas and oligodendrogliomas.

  12. Reverse engineering of modified genes by Bayesian network analysis defines molecular determinants critical to the development of glioblastoma.

    Directory of Open Access Journals (Sweden)

    Brian W Kunkle

    Full Text Available In this study we have identified key genes that are critical in development of astrocytic tumors. Meta-analysis of microarray studies which compared normal tissue to astrocytoma revealed a set of 646 differentially expressed genes in the majority of astrocytoma. Reverse engineering of these 646 genes using Bayesian network analysis produced a gene network for each grade of astrocytoma (Grade I-IV, and 'key genes' within each grade were identified. Genes found to be most influential to development of the highest grade of astrocytoma, Glioblastoma multiforme were: COL4A1, EGFR, BTF3, MPP2, RAB31, CDK4, CD99, ANXA2, TOP2A, and SERBP1. All of these genes were up-regulated, except MPP2 (down regulated. These 10 genes were able to predict tumor status with 96-100% confidence when using logistic regression, cross validation, and the support vector machine analysis. Markov genes interact with NFkβ, ERK, MAPK, VEGF, growth hormone and collagen to produce a network whose top biological functions are cancer, neurological disease, and cellular movement. Three of the 10 genes - EGFR, COL4A1, and CDK4, in particular, seemed to be potential 'hubs of activity'. Modified expression of these 10 Markov Blanket genes increases lifetime risk of developing glioblastoma compared to the normal population. The glioblastoma risk estimates were dramatically increased with joint effects of 4 or more than 4 Markov Blanket genes. Joint interaction effects of 4, 5, 6, 7, 8, 9 or 10 Markov Blanket genes produced 9, 13, 20.9, 26.7, 52.8, 53.2, 78.1 or 85.9%, respectively, increase in lifetime risk of developing glioblastoma compared to normal population. In summary, it appears that modified expression of several 'key genes' may be required for the development of glioblastoma. Further studies are needed to validate these 'key genes' as useful tools for early detection and novel therapeutic options for these tumors.

  13. Primary cerebellar glioblastoma multiforme.

    Science.gov (United States)

    Demir, Mustafa Kemal; Hakan, Tayfun; Akinci, Okan; Berkman, Zafer

    2005-06-01

    Primary glioblastoma multiforme of cerebellar hemispheres in adults is a rare condition. Most of them result from dedifferentiation of astrocytoma to glioblastoma. We present two cases of unusual de novo cerebellar glioblastomas, one of which is the giant-cell variant. We review their clinical behaviour with conventional MR imaging features and discuss the key findings that can lead to the correct diagnosis in sight of new MR imaging technologies.

  14. Analysis of Brain Tumors Due to the Usage of Mobile Phones

    OpenAIRE

    SOOBIA SAEED; ASADULLAH SHAIKH; SHABAZ AHMED NOOR

    2017-01-01

    The impact of cellular phone radiation on human health is the subject of current mindfulness and is an outcome of the huge increase in phone usage throughout the world. Phones use electromagnetic radiation in the microwave range. The issue is associated with wireless use for 50 minutes and above. The excessive use of mobile phone may cause brain tumors. Nowadays the most commonly developed brain tumor type is GBM (Glioblastoma) in multiform and Malignant Astrocytoma. In this paper, we focus ...

  15. The right amygdalar tumor presenting with symptoms of separation anxiety disorder (SAD): a case report.

    Science.gov (United States)

    Chen, Huang-Chen; Lin, Chun-Fu; Lee, Ying-Chiao

    2015-01-01

    A patient with an astrocytoma of the right-sided amygdala developed symptoms of separation anxiety disorders (SADs). These symptoms significantly subsided after tumor resection. The temporal relationship suggested that the amygdalar tumor could result in the specific symptoms. To our knowledge, this is the first report of SAD as one manifestation of the amygdalar tumor. The tumorigenesis of amygdala resulted in impaired regulation and abnormal activity associated with anticipating anxiety and conditioning. It deserves clinical attention to early detection and intervention.

  16. Pathology, Molecular Genetics, and Epigenetics of Diffuse Intrinsic Pontine Glioma

    OpenAIRE

    Buczkowicz, Pawel; Hawkins, Cynthia

    2015-01-01

    Diffuse intrinsic pontine glioma (DIPG) is a devastating pediatric brain cancer with no effective therapy. Histological similarity of DIPG to supratentorial high-grade astrocytomas of adults has led to assumptions that these entities possess similar underlying molecular properties and therefore similar therapeutic responses to standard therapies. The failure of all clinical trials in the last 30 years to improve DIPG patient outcome has suggested otherwise. Recent studies employing next-gener...

  17. Two-year drinking water carcinogenicity study of methyl tertiary-butyl ether (MTBE) in Wistar rats.

    Science.gov (United States)

    Dodd, Darol; Willson, Gabrielle; Parkinson, Horace; Bermudez, Edilberto

    2013-07-01

    Methyl tertiary-butyl ether (MTBE) has been used as a gasoline additive to reduce tailpipe emissions and its use has been discontinued. There remains a concern that drinking water sources have been contaminated with MTBE. A two-year drinking water carcinogenicity study of MTBE was conducted in Wistar rats (males, 0, 0.5, 3, 7.5 mg ml(-1); and females, 0, 0.5, 3, and 15 mg ml(-1)). Body weights were unaffected and water consumption was reduced in MTBE-exposed males and females. Wet weights of male kidneys were increased at the end of two years of exposure to 7.5 mg ml(-1) MTBE. Chronic progressive nephropathy was observed in males and females, was more severe in males, and was exacerbated in the high MTBE exposure groups. Brain was the only tissue with a statistically significant finding of neoplasms. One astrocytoma (1/50) was found in a female rat (15 mg ml(-1)). The incidence of brain astrocytomas in male rats was 1/50, 1/50, 1/50 and 4/50 for the 0, 0.5, 3 and 7.5 mg ml(-1) exposure groups, respectively. This was a marginally significant statistical trend, but not statistically significant when pairwise comparisons were made or when multiple comparisons were taken into account. The incidence of astrocytoma fell within historical control ranges for Wistar rats, and the brain has not been identified as a target organ following chronic administration of MTBE, ethyl tert-butyl ether, or tertiary butyl alcohol (in drinking water) to mice and rats. We conclude that the astrocytomas observed in this study are not associated with exposure to MTBE. Copyright © 2011 John Wiley & Sons, Ltd.

  18. Impact of MACC1 on human malignant glioma progression and patients' unfavorable prognosis.

    Science.gov (United States)

    Hagemann, Carsten; Fuchs, Steffen; Monoranu, Camelia M; Herrmann, Pia; Smith, Janice; Hohmann, Tim; Grabiec, Urszula; Kessler, Almuth F; Dehghani, Faramarz; Löhr, Mario; Ernestus, Ralf-Ingo; Vince, Giles H; Stein, Ulrike

    2013-12-01

    Metastasis-associated in colon cancer 1 (MACC1) has been established as an independent prognostic indicator of metastasis formation and metastasis-free survival for patients with colon cancer and other solid tumors. However, no data are available concerning MACC1 expression in human astrocytic tumors. Glioblastoma multiforme (GBM) is the most prevalent primary brain tumor of adulthood, and due to its invasive and rapid growth, patients have unfavorable prognoses. Although these tumors rarely metastasize, their invasive and migratory behavior is similar to those of metastatic cells of tumors of different origin. Thus, we hypothesized that MACC1 may be involved in progression of human gliomas. We performed real-time measurements of proliferation and migration in MACC1-transfected GBM cell lines (U138, U251) and evaluated tumor formation in organotypic hippocampal slice cultures of mice. Semiquantitative and quantitative real-time reverse transcription PCR analyses were performed for MACC1 and for its transcriptional target c-Met in human astrocytoma of World Health Organization grade II (low-grade astrocytoma) and GBM biopsies. Data were validated by MACC1 immunohistochemistry in independent matched samples of low-grade astrocytoma and GBM. MACC1 increases the proliferative, migratory, and tumor-formation abilities of GBM cells. The c-Met inhibitor crizotinib reduced MACC1-induced migration and tumor formation in organotypic hippocampal slice cultures of mice. Analyzing patients' biopsies, MACC1 expression increased concomitantly with increasing World Health Organization grade. Moreover, MACC1 expression levels allowed discrimination of dormant and recurrent low-grade astrocytomas and of primary and secondary GBM. Strong MACC1 expression correlated with reduced patient survival. MACC1 may represent a promising biomarker for prognostication and a new target for treatment of human gliomas.

  19. Prechiasmatic transection of the optic nerve in optic nerve glioma: technical description and surgical outcome.

    Science.gov (United States)

    Borghei-Razavi, Hamid; Shibao, Shunsuke; Schick, Uta

    2017-01-01

    Optic pathway glioma (OPG) encompasses a spectrum of findings ranging from lesions confined to the optic nerve only, lesions affecting the optic chiasm and hypothalamus, and lesions with diffuse involvement of a large part of the optic pathway and neighboring structures. The majority of pediatric low-grade astrocytomas in the optic/chiasmatic region are typical pilocytic astrocytoma. The rest of them (10 %) may be other gliomas such as fibrillary pilomyxoid astrocytoma (grade 2 WHO). The postsurgical local recurrence rate of 55 to 76 % has been reported in some histological subtypes such as pilomyxoid astrocytoma (grade 2). Performing a prechiasmatic transection might offer a new surgical option to avoid further tumor growth toward the chiasm in the optic nerve glioma with predominantly orbital manifestations. In this retrospective study, four patients (three children, two without neurofibromatosis type 1 (NF1), and one with NF1 and one adult without NF1) with optic nerve glioma without involvement of the chiasm but blindness, disfiguring proptosis, and pain of the affected eye were included. The surgical approach was performed as a combined approach from pterional extradural and intradural. Without any exceptions, vision of the contralateral eye could be preserved and did not show any deterioration after surgery or during the follow-up time between 17 and 106 months. Furthermore, in all patients, gross total tumor resection could be achieved. During follow-up observation in all patients, no further tumor progress or recurrences could be observed. None of the patients were treated postoperatively by radiotherapy or chemotherapy. Prechiasmatic transection of the optic nerve in optic nerve glioma without affecting the chiasm might offer a surgical treatment option to control tumor growth and to preserve vision of the contralateral eye.

  20. A PROSPECTIVE HISTOPATHOLOGICAL-BASED STUDY OF BRAIN TUMOURS IN A REFERRAL CENTRE

    OpenAIRE

    Prathima Gujjaru; N. Saila Rekha; Syam Sunder Rao Uttarakar

    2016-01-01

    BACKGROUND Brain neoplasms occur at all ages and account for around 2-3 percent of all deaths in adults. In children, the frequency increases to more than twenty percent. In children, it forms the second most common type of malignancy. Most of the tumours encountered are not related to any identifiable risk factors except for irradiation and some hereditary syndromes like subependymal giant cell astrocytoma, glioblastoma multiforme, cerebellar haemangioblastoma, meningioma, Sc...

  1. Gamma-Secretase Inhibitor RO4929097 in Treating Young Patients With Relapsed or Refractory Solid Tumors, CNS Tumors, Lymphoma, or T-Cell Leukemia

    Science.gov (United States)

    2014-11-04

    Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Choriocarcinoma; Childhood Central Nervous System Germinoma; Childhood Central Nervous System Mixed Germ Cell Tumor; Childhood Central Nervous System Teratoma; Childhood Central Nervous System Yolk Sac Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood Infratentorial Ependymoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Gonadotroph Adenoma; Pituitary Basophilic Adenoma; Pituitary Chromophobe Adenoma; Pituitary Eosinophilic Adenoma; Prolactin Secreting Adenoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Central Nervous System Embryonal Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Spinal Cord Neoplasm; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Recurrent Pituitary Tumor; Recurrent/Refractory Childhood Hodgkin Lymphoma; T-cell Childhood Acute Lymphoblastic Leukemia; T-cell Large Granular Lymphocyte Leukemia; TSH Secreting Adenoma; Unspecified Childhood Solid Tumor, Protocol Specific

  2. Putative Structural and Functional Coupling of the Mitochondrial BKCa Channel to the Respiratory Chain.

    Directory of Open Access Journals (Sweden)

    Piotr Bednarczyk

    Full Text Available Potassium channels have been found in the inner mitochondrial membranes of various cells. These channels regulate the mitochondrial membrane potential, the matrix volume and respiration. The activation of these channels is cytoprotective. In our study, the single-channel activity of a large-conductance Ca(2+-regulated potassium channel (mitoBKCa channel was measured by patch-clamping mitoplasts isolated from the human astrocytoma (glioblastoma U-87 MG cell line. A potassium-selective current was recorded with a mean conductance of 290 pS in symmetrical 150 mM KCl solution. The channel was activated by Ca(2+ at micromolar concentrations and by the potassium channel opener NS1619. The channel was inhibited by paxilline and iberiotoxin, known inhibitors of BKCa channels. Western blot analysis, immuno-gold electron microscopy, high-resolution immunofluorescence assays and polymerase chain reaction demonstrated the presence of the BKCa channel β4 subunit in the inner mitochondrial membrane of the human astrocytoma cells. We showed that substrates of the respiratory chain, such as NADH, succinate, and glutamate/malate, decrease the activity of the channel at positive voltages. This effect was abolished by rotenone, antimycin and cyanide, inhibitors of the respiratory chain. The putative interaction of the β4 subunit of mitoBKCa with cytochrome c oxidase was demonstrated using blue native electrophoresis. Our findings indicate possible structural and functional coupling of the mitoBKCa channel with the mitochondrial respiratory chain in human astrocytoma U-87 MG cells.

  3. Addition of IFN-{alpha}to treatment of malignant brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Jereb, B. [Clinical Center, Ljubljana (Slovenia). Inst. of Oncology; Petric-Grabnar, G. [Clinical Center, Ljubljana (Slovenia). Inst. of Oncology; Klun, B. [Clinical Center, Ljubljana (Slovenia). Clinic of Neurosurgery; Lamovec, J. [Clinical Center, Ljubljana (Slovenia). Inst. of Oncology; Skrbec, M. [Clinical Center, Ljubljana (Slovenia). Inst. of Radiology; Soos, E. [Inst. of Immunology, Zagreb (Croatia)

    1994-12-31

    Despite many attempts to improve the survival after surgery of patients with malignant astrocytoma the prognosis is poor. We have used natural IFN-{alpha} in 16 patients with malignant astrocytoma treated between 1987 and 1990; 6 for recurrent tumors. Radiation therapy was given in 2 Gy fractions daily to a total dose of 50 Gy in the tumor area, 5 fractions per week and IFN twice per week, cisplatinum 60 mg/m{sup 2} i.v. every second week and vincristine 2 mg every week in 12-h i.v. infusions. Eight patients were reoperated when clinical deterioration suggested recurrent tumor; histological examination showed no residual tumor in 7 of them. Of these 8 patients 3 are alive and well, 2 of them after more than 5 years. The study suggests that malignant astrocytoma can be successfully eradicated with surgery, irradiation, IFN-{alpha} and chemotherapy. The treatment had, however, unacceptably high neurotoxicity. Earlier removal of the tumor necrosis, before clinical deterioration, could possibly diminish the high complication rate and consequently improve survival. (orig.).

  4. Expression of iron-related genes in human brain and brain tumors

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    Britton Robert S

    2009-04-01

    Full Text Available Abstract Background Defective iron homeostasis may be involved in the development of some diseases within the central nervous system. Although the expression of genes involved in normal iron balance has been intensively studied in other tissues, little is known about their expression in the brain. We investigated the mRNA levels of hepcidin (HAMP, HFE, neogenin (NEO1, transferrin receptor 1 (TFRC, transferrin receptor 2 (TFR2, and hemojuvelin (HFE2 in normal human brain, brain tumors, and astrocytoma cell lines. The specimens included 5 normal brain tissue samples, 4 meningiomas, one medulloblastoma, 3 oligodendrocytic gliomas, 2 oligoastrocytic gliomas, 8 astrocytic gliomas, and 3 astrocytoma cell lines. Results Except for hemojuvelin, all genes studied had detectable levels of mRNA. In most tumor types, the pattern of gene expression was diverse. Notable findings include high expression of transferrin receptor 1 in the hippocampus and medulla oblongata compared to other brain regions, low expression of HFE in normal brain with elevated HFE expression in meningiomas, and absence of hepcidin mRNA in astrocytoma cell lines despite expression in normal brain and tumor specimens. Conclusion These results indicate that several iron-related genes are expressed in normal brain, and that their expression may be dysregulated in brain tumors.

  5. Remote intracranial recurrence of IDH mutant gliomas is associated with TP53 mutations and an 8q gain

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    Nakae, Shunsuke; Kato, Takema; Murayama, Kazuhiro; Sasaki, Hikaru; Abe, Masato; Kumon, Masanobu; Kumai, Tadashi; Yamashiro, Kei; Inamasu, Joji; Hasegawa, Mitsuhiro; Kurahashi, Hiroki; Hirose, Yuichi

    2017-01-01

    Most IDH mutant gliomas harbor either 1p/19q co-deletions or TP53 mutation; 1p/19q co-deleted tumors have significantly better prognoses than tumors harboring TP53 mutations. To investigate the clinical factors that contribute to differences in tumor progression of IDH mutant gliomas, we classified recurrent tumor patterns based on MRI and correlated these patterns with their genomic characterization. Accordingly, in IDH mutant gliomas (N = 66), 1p/19 co-deleted gliomas only recurred locally, whereas TP53 mutant gliomas recurred both locally and in remote intracranial regions. In addition, diffuse tensor imaging suggested that remote intracranial recurrence in the astrocytomas, IDH-mutant with TP53 mutations may occur along major fiber bundles. Remotely recurrent tumors resulted in a higher mortality and significantly harbored an 8q gain; astrocytomas with an 8q gain resulted in significantly shorter overall survival than those without an 8q gain. OncoScan® arrays and next-generation sequencing revealed specific 8q regions (i.e., between 8q22 and 8q24) show a high copy number. In conclusion, only tumors with TP53 mutations showed patterns of remote recurrence in IDH mutant gliomas. Furthermore, an 8q gain was significantly associated with remote intracranial recurrence and can be considered a poor prognostic factor in astrocytomas, IDH-mutant. PMID:29156679

  6. Remote intracranial recurrence ofIDHmutant gliomas is associated withTP53mutations and an 8q gain.

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    Nakae, Shunsuke; Kato, Takema; Murayama, Kazuhiro; Sasaki, Hikaru; Abe, Masato; Kumon, Masanobu; Kumai, Tadashi; Yamashiro, Kei; Inamasu, Joji; Hasegawa, Mitsuhiro; Kurahashi, Hiroki; Hirose, Yuichi

    2017-10-17

    Most IDH mutant gliomas harbor either 1p/19q co-deletions or TP53 mutation; 1p/19q co-deleted tumors have significantly better prognoses than tumors harboring TP53 mutations. To investigate the clinical factors that contribute to differences in tumor progression of IDH mutant gliomas, we classified recurrent tumor patterns based on MRI and correlated these patterns with their genomic characterization. Accordingly, in IDH mutant gliomas ( N = 66), 1p/19 co-deleted gliomas only recurred locally, whereas TP53 mutant gliomas recurred both locally and in remote intracranial regions. In addition, diffuse tensor imaging suggested that remote intracranial recurrence in the astrocytomas, IDH-mutant with TP53 mutations may occur along major fiber bundles. Remotely recurrent tumors resulted in a higher mortality and significantly harbored an 8q gain; astrocytomas with an 8q gain resulted in significantly shorter overall survival than those without an 8q gain. OncoScan ® arrays and next-generation sequencing revealed specific 8q regions (i.e., between 8q22 and 8q24) show a high copy number. In conclusion, only tumors with TP53 mutations showed patterns of remote recurrence in IDH mutant gliomas. Furthermore, an 8q gain was significantly associated with remote intracranial recurrence and can be considered a poor prognostic factor in astrocytomas, IDH-mutant.

  7. Real-time quantitative PCR analysis of regions involved in gene amplification reveals gene overdose in low-grade astrocytic gliomas.

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    Arjona, Dolores; Bello, M Josefa; Alonso, M Eva; Isla, Alberto; De Campos, Jose M; Vaquero, Jesus; Sarasa, Jose L; Gutierrez, Manuel; Rey, Juan A

    2005-12-01

    We have studied gene amplification of genes located in 1q32 (GAC1, ELF3, MDM4, and ren1), 4q11 (PDGFR-alpha), and in 12q13-14 (MDM2 and CDK4) using quantitative real-time PCR in a group of 86 tumors consisting of 44 WHO grade IV glioblastomas (GBM) (34 primary and 10 secondary tumors), 21 WHO grade III anaplastic astrocytomas (AA), and 21 WHO grade II astrocytomas (AII). Gene amplification was present in 56 of the 86 samples (65%) in at least 1 gene in our series. GAC1 (51%) and MDM4 (27%) were the most frequently amplified genes within the 1q32 amplicon, and their higher amplification frequency was statistically significant (P<0.05, chi) in the low-grade astrocytomas. Concordant co-amplification was determined for ELF3 and ren1 or ren1 and MDM4 in the grade III-IV tumors. MDM2 amplification was significantly more frequent in primary GBM (16%) than was in secondary GBM (0%). The present study shows that gene amplification in the studied regions is already present in low-grade astrocytic tumors and that amplification of some genes may represent another molecular marker to differentiate primary from secondary GBM.

  8. [Value of the nucleolar organizers (AgNOR) in brain gliomas].

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    Ducrot, P; Joundi, A; Diebold, M D; Pluot, M

    1991-01-01

    The aim of the study was to evaluate the feasibility and possible contribution of silver stained nucleolar organizer regions (AgNORs) to prognostic considerations, in a series of 55 supratentorial gliomas: eight grade II astrocytomas, twelve grade III astrocytomas, thirty grade IV astrocytomas, two glioblastomas, one anaplastic oligodendroglioma, one oligodendroglioma and one ependymoma. Silver NORs (AgNORs) were demonstrated according to the method of Crocker et al. A difference between AgNOR sizes in peritumor and tumor tissue is noted. The mean NOR numbers in the tumor areas range from 0.871 to 2.677, without overlap between peritumor gliosis and glial tumors. A comparative analysis reveals significant correlations between the mean NOR number per nucleus and histological grading. This technique can play a practical role in the diagnosis and grading of tumors sampled by stereotactic biopsies: a count higher than 0.8 is highly suggestive of malignancy. In addition, the distribution of NORs may be important: intratumoral heterogeneity expresses various degrees of transcriptional activity between different glial tumors of the same grade. This technique provides information about the biological behaviour of glial tumors supplementary to that obtained from growth fraction analysis.

  9. Immunohistochemical characterization of spontaneous and acrylonitrile-induced brain tumors in the rat.

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    Kolenda-Roberts, Holly Meredith; Harris, Nancy; Singletary, Emily; Hardisty, Jerry F

    2013-01-01

    Twenty-eight spontaneously occurring glial tumors (previously diagnosed as astrocytomas, oligodendrogliomas, and gliomas) and eleven granular cell tumors (GCTs) were selected for evaluation using a panel of immunohistochemistry (IHC) stains (Ricinus communis agglutinin type 1 [RCA-1], ionized calcium-binding adapter molecule 1 [Iba-1], OX-6/major immunohistocompatibility complex class II, oligodendrocytes transcription factor 2 [Olig2], glial fibrillary acidic protein [GFAP], S100 beta, glutamine synthetase, neurofilament, proliferating cell nuclear antigen). In addition, nine brain tumors from a 2-year drinking water study for acrylonitrile were obtained from the Acrylonitrile Group, Inc. Based on IHC staining characteristics, Olig2+ oligodendrogliomas were the most commonly diagnosed spontaneous tumor in these animals. Many of the spontaneous tumors previously diagnosed as astrocytomas were RCA-1+, Iba-1+ and negative for GFAP, S100beta, and glutamine synthetase; the diagnosis of malignant microglial tumor is proposed for these neoplasms. Three mixed tumors were identified with Olig2+ (oligodendrocytes) and Iba-1+ (macrophage/microglia) cell populations. The term mixed glioma is not recommended for these tumors, as it is generally used to refer to oligoastrocytomas, which were not observed in this study. GCT were positive for RCA-1 and Iba-1. All acrylonitrile tumors were identified as malignant microglial tumors. These results may indicate that oligodendrogliomas are more common as spontaneous tumors, while acrylonitrile-induced neoplasms are microglial/histiocytic in origin. No astrocytomas (GFAP, S100 beta, and/or glutamine synthetase-positive neoplasms) were observed.

  10. Differential expression of ID4 and its association with TP53 mutation, SOX2, SOX4 and OCT-4 expression levels.

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    Thais Fernanda de Almeida Galatro

    Full Text Available Inhibitor of DNA Binding 4 (ID4 is a member of the helix-loop-helix ID family of transcription factors, mostly present in the central nervous system during embryonic development, that has been associated with TP53 mutation and activation of SOX2. Along with other transcription factors, ID4 has been implicated in the tumorigenic process of astrocytomas, contributing to cell dedifferentiation, proliferation and chemoresistance. In this study, we aimed to characterize the ID4 expression pattern in human diffusely infiltrative astrocytomas of World Health Organization (WHO grades II to IV of malignancy (AGII-AGIV; to correlate its expression level to that of SOX2, SOX4, OCT-4 and NANOG, along with TP53 mutational status; and to correlate the results with the clinical end-point of overall survival among glioblastoma patients. Quantitative real time PCR (qRT-PCR was performed in 130 samples of astrocytomas for relative expression, showing up-regulation of all transcription factors in tumor cases. Positive correlation was found when comparing ID4 relative expression of infiltrative astrocytomas with SOX2 (r = 0.50; p<0.005, SOX4 (r = 0.43; p<0.005 and OCT-4 (r = 0.39; p<0.05. The results from TP53 coding exon analysis allowed comparisons between wild-type and mutated status only in AGII cases, demonstrating significantly higher levels of ID4, SOX2 and SOX4 in mutated cases (p<0.05. This pattern was maintained in secondary GBM and further confirmed by immunohistochemistry, suggesting a role for ID4, SOX2 and SOX4 in early astrocytoma tumorigenesis. Combined hyperexpression of ID4, SOX4 and OCT-4 conferred a much lower (6 months median survival than did hypoexpression (18 months. Because both ID4 alone and a complex of SOX4 and OCT-4 activate SOX2 transcription, it is possible that multiple activation of SOX2 impair the prognosis of GBM patients. These observational results of associated expression of ID4 with SOX4 and OCT-4 may be used as a

  11. Tumour risk associated with use of cellular telephones or cordless desktop telephones

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    Söderqvist Fredrik

    2006-10-01

    Full Text Available Abstract Background The use of cellular and cordless telephones has increased dramatically during the last decade. There is concern of health problems such as malignant diseases due to microwave exposure during the use of these devices. The brain is the main target organ. Methods Since the second part of the 1990's we have performed six case-control studies on this topic encompassing use of both cellular and cordless phones as well as other exposures. Three of the studies concerned brain tumours, one salivary gland tumours, one non-Hodgkin lymphoma (NHL and one testicular cancer. Exposure was assessed by self-administered questionnaires. Results Regarding acoustic neuroma analogue cellular phones yielded odds ratio (OR = 2.9, 95 % confidence interval (CI = 2.0–4.3, digital cellular phones OR = 1.5, 95 % CI = 1.1–2.1 and cordless phones OR = 1.5, 95 % CI = 1.04–2.0. The corresponding results were for astrocytoma grade III-IV OR = 1.7, 95 % CI = 1.3–2.3; OR = 1.5, 95 % CI = 1.2–1.9 and OR = 1.5, 95 % CI = 1.1–1.9, respectively. The ORs increased with latency period with highest estimates using > 10 years time period from first use of these phone types. Lower ORs were calculated for astrocytoma grade I-II. No association was found with salivary gland tumours, NHL or testicular cancer although an association with NHL of T-cell type could not be ruled out. Conclusion We found for all studied phone types an increased risk for brain tumours, mainly acoustic neuroma and malignant brain tumours. OR increased with latency period, especially for astrocytoma grade III-IV. No consistent pattern of an increased risk was found for salivary gland tumours, NHL, or testicular cancer.

  12. Molecular Alterations of KIT Oncogene in Gliomas

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    Ana L. Gomes

    2007-01-01

    Full Text Available Gliomas are the most common and devastating primary brain tumours. Despite therapeutic advances, the majority of gliomas do not respond either to chemo or radiotherapy. KIT, a class III receptor tyrosine kinase (RTK, is frequently involved in tumourigenic processes. Currently, KIT constitutes an attractive therapeutic target. In the present study we assessed the frequency of KIT overexpression in gliomas and investigated the genetic mechanisms underlying KIT overexpression. KIT (CD117 immunohistochemistry was performed in a series of 179 gliomas of various grades. KIT activating gene mutations (exons 9, 11, 13 and 17 and gene amplification analysis, as defined by chromogenic in situ hybridization (CISH and quantitative real-time PCR (qRT-PCR were performed in CD117 positive cases. Tumour cell immunopositivity was detected in 15.6% (28/179 of cases, namely in 25% (1/4 of pilocytic astrocytomas, 25% (5/20 of diffuse astrocytomas, 20% (1/5 of anaplastic astrocytomas, 19.5% (15/77 of glioblastomas and one third (3/9 of anaplastic oligoastrocytomas. Only 5.7% (2/35 of anaplastic oligodendrogliomas showed CD117 immunoreactivity. No association was found between tumour CD117 overexpression and patient survival. In addition, we also observed CD117 overexpression in endothelial cells, which varied from 0–22.2% of cases, being more frequent in high-grade lesions. No KIT activating mutations were identified. Interestingly, CISH and/or qRT-PCR analysis revealed the presence of KIT gene amplification in 6 glioblastomas and 2 anaplastic oligoastrocytomas, corresponding to 33% (8/24 of CD117 positive cases. In conclusion, our results demonstrate that KIT gene amplification rather than gene mutation is a common genetic mechanism underlying KIT expression in subset of malignant gliomas. Further studies are warranted to determine whether glioma patients exhibiting KIT overexpression and KIT gene amplification may benefit from therapy with anti-KIT RTK

  13. Seizure prognosis of patients with low-grade tumors.

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    Kahlenberg, Cynthia A; Fadul, Camilo E; Roberts, David W; Thadani, Vijay M; Bujarski, Krzysztof A; Scott, Rod C; Jobst, Barbara C

    2012-09-01

    Seizures frequently impact the quality of life of patients with low grade tumors. Management is often based on best clinical judgment. We examined factors that correlate with seizure outcome to optimize seizure management. Patients with supratentorial low-grade tumors evaluated at a single institution were retrospectively reviewed. Using multiple regression analysis the patient characteristics and treatments were correlated with seizure outcome using Engel's classification. Of the 73 patients with low grade tumors and median follow up of 3.8 years (range 1-20 years), 54 (74%) patients had a seizure ever and 46 (63%) had at least one seizure before tumor surgery. The only factor significantly associated with pre-surgical seizures was tumor histology. Of the 54 patients with seizures ever, 25 (46.3%) had a class I outcome at last follow up. There was no difference in seizure outcome between grade II gliomas (astrocytoma grade II, oligodendroglioma grade II, mixed oligo-astrocytoma grade II) and other pathologies (pilocytic astrocytoma, ependymomas, DNET, gangliocytoma and ganglioglioma). Once seizures were established seizure prognosis was similar between different pathologies. Chemotherapy (p=0.03) and radiation therapy (p=0.02) had a positive effect on seizure outcome. No other parameter including significant tumor growth during the follow up period predicted seizure outcome. Only three patients developed new-onset seizures after tumor surgery that were non-perioperative. Anticonvulsant medication was tapered in 14 patients with seizures and 10 had no further seizures. Five patients underwent additional epilepsy surgery with a class I outcome in four. Two patients received a vagal nerve stimulator with >50% seizure reduction. Seizures at presentation are the most important factor associated with continued seizures after tumor surgery. Pathology does not influence seizure outcome. Use of long term prophylactic anticonvulsants is unwarranted. Chemotherapy and

  14. ADAM 12: A Putative Marker of Oligodendrogliomas?

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    Dimitrios Kanakis

    2013-01-01

    Full Text Available ADAM 12 (meltrin alpha belongs to a large family of molecules, consisting of members with both disintegrin and metalloproteinase properties. ADAMs have been implicated in several cell physiological processes including cell adhesion, cell fusion, proteolysis and signalling. ADAM 12 is widely expressed, including skeletal muscle, testis, bone, intestine, heart and kidney. In addition, a variety of tumours show elevated expression of ADAM12; among them being breast-, colon-, gastric- and lung-carcinoma. As to the brain, ADAM 12 has been shown previously to be expressed in rat and human oligodendrocytes. However, little is known about the expression of this protease in brain tumours. This study demonstrates the presence of ADAM 12 in non-neoplastic oligodendroglial cells of normal human brain as well as in neoplastic oligodendroglia and minigemistocytes arising from four pure oligodendrogliomas and three mixed oligoastrocytomas. Double stainings revealed a notable preference of ADAM 12 for the oligodendroglial over astroglial components. The results of immunohistochemistry are in accordance with the results obtained from the RT-PCR, which further demonstrated a mild difference concerning the mRNA concentration of ADAM 12 between similar grades of eight astrocytomas and eight oligodendrogliomas (namely four astrocytomas grade II versus four oligodendrogliomas grade II and four astrocytomas grade III versus four oligodendrogliomas grade III. Both cellular immunostaining for ADAM 12 and ADAM 12 mRNA content decrease with higher histologic grade of the tumour. Surprisingly, the latter parameter (ADAM12 mRNA showed a significant opposite correlation to the degree of histologic tumour malignancy. From our data showing that ADAM 12 is highly expressed in, but not restricted to, oligodendrogliomas, we conclude that ADAM 12 immunohistochemistry may be a helpful tool in the diagnosis of brain tumours.

  15. SU-D-207A-02: Possible Characterization of the Brain Tumor Vascular Environment by a Novel Strategy of Quantitative Analysis in Dynamic Contrast Enhanced MR Imaging: A Combination of Both Patlak and Logan Analyses

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    Yee, S; Chinnaiyan, P; Wloch, J; Pirkola, M; Yan, D [Beaumont Health System, Royal Oak, MI (United States)

    2016-06-15

    Purpose: The majority of quantitative analyses involving dynamic contrast enhanced (DCE) MRI have been performed to obtain kinetic parameters such as Ktrans and ve. Such analyses are generally performed assuming a “reversible” tissue compartment, where the tracer is assumed to be rapidly equilibrated between the plasma and tissue compartments. However, some tumor vascular environments may be more suited for a “non-reversible” tissue compartment, where, as with FDG PET imaging, the tracer is continuously deposited into the tissue compartment (or the return back to the plasma compartment is very slow in the imaging time scale). Therefore, Patlak and Logan analyses, which represent tools for the “non-reversible” and “reversible” modeling, respectively, were performed to better characterize the brain tumor vascular environment. Methods: A voxel-by-voxel analysis was performed to generate both Patlak and Logan plots in two brain tumor patients, one with grade III astrocytoma and the other with grade IV astrocytoma or glioblastoma. The slopes of plots and the r-square were then obtained by linear fitting and compared for each voxel. Results: The 2-dimensional scatter plots of Logan (Y-axis) vs. Patlak slopes (X-axis) clearly showed increased Logan slopes for glioblastoma (Figure 3A). The scatter plots of goodness-of-fit (Figure 3B) also suggested glioblastoma, relative to grade III astrocytoma, might consist of more voxels that are kinetically Logan-like (i.e. rapidly equilibrated extravascular space and active vascular environment). Therefore, the enhanced Logan-like behavior (and the Logan slope) in glioblastoma may imply an increased fraction of active vascular environment, while the enhanced Patlak-like behavior implies the vascular environment permitting a relatively slower washout of the tracer. Conclusion: Although further verification is required, the combination of Patlak and Logan analyses in DCE MRI may be useful in characterizing the tumor

  16. Clonal mutations in primary human glial tumors: evidence in support of the mutator hypothesis

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    Sarkar Chitra

    2007-10-01

    Full Text Available Abstract Background A verifiable consequence of the mutator hypothesis is that even low grade neoplasms would accumulate a large number of mutations that do not influence the tumor phenotype (clonal mutations. In this study, we have attempted to quantify the number of clonal mutations in primary human gliomas of astrocytic cell origin. These alterations were identified in tumor tissue, microscopically confirmed to have over 70% neoplastic cells. Methods Random Amplified Polymorphic DNA (RAPD analysis was performed using a set of fifteen 10-mer primers of arbitrary but definite sequences in 17 WHO grade II astrocytomas (low grade diffuse astrocytoma or DA and 16 WHO grade IV astrocytomas (Glioblastoma Multiforme or GBM. The RAPD profile of the tumor tissue was compared with that of the leucocyte DNA of the same patient and alteration(s scored. A quantitative estimate of the overall genomic changes in these tumors was obtained by 2 different modes of calculation. Results The overall change in the tumors was estimated to be 4.24% in DA and 2.29% in GBM by one method and 11.96% and 6.03% in DA and GBM respectively by the other. The difference between high and lower grade tumors was statistically significant by both methods. Conclusion This study demonstrates the presence of extensive clonal mutations in gliomas, more in lower grade. This is consistent with our earlier work demonstrating that technique like RAPD analysis, unbiased for locus, is able to demonstrate more intra-tumor genetic heterogeneity in lower grade gliomas compared to higher grade. The results support the mutator hypothesis proposed by Loeb.

  17. Prognostic value of epidermal growth factor receptor amplification and EGFRvIII in glioblastoma: meta-analysis.

    Science.gov (United States)

    Chen, J-R; Xu, H-Z; Yao, Y; Qin, Z-Y

    2015-11-01

    Epidermal growth factor receptor (EGFR) gene amplification and the EGFRvIII mutation may have prognostic value in patients with glioblastoma. This meta-analysis was to determine whether EGFR gene amplification or the EGFRvIII mutation are predictors of survival in patients with glioblastoma and anaplastic astrocytoma. Medline, the Cochrane Central Register of Controlled Trials, EMBASE, and Google Scholar databases were searched until July 31, 2014. Studies were selected for inclusion in the analysis if they included patients with anaplastic astrocytoma and/or glioblastoma, EGFR and/or EGFRvIII mutation status was reported, and overall survival (OS) data were reported. Of 113 articles initially identified, only eight contained data with respect to the outcome of interest and were included in the meta-analysis. The number of cases ranged from 14 to 268, and the majority of patients were 60 or more years of age. There was no significant difference in OS between EGFR amplification-positive and EGFR amplification-negative glioblastoma patients (pooled hazard ratio [HR] = 1.101, 95% confidence interval [CI] 0.845, 1.434, P = 0.475) or anaplastic astrocytoma patients (pooled HR = 1.455, 95% CI 0.852, 2.482, P = 0.169). There was no significant difference in OS between EGFRvIII-positive and EGFRvIII-negative glioblastoma patients (pooled HR = 1.321, 95% CI: 0.881-1.981, P = 0.178). Significant heterogeneity existed between the studies, and the significance changed when the analysis was performed with studies removed in turn. There is insufficient evidence that either EGFR amplification or the EGFRvIII mutation has prognostic value in patients with glioblastoma. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Fluorescence-guided surgery in high grade gliomas using an exoscope system.

    Science.gov (United States)

    Belloch, José Piquer; Rovira, Vicente; Llácer, Jose L; Riesgo, Pedro A; Cremades, Antonio

    2014-04-01

    Fluorescence-guided microsurgical resections of high-grade gliomas using 5-aminolevulinic acid (5-ALA) is superior to conventional microsurgery. An optical device, usually a modified microscope, is needed for these procedures. However, an exoscope may be implemented for fluorescence techniques. We present the use of an exoscope to perform tumor resection guided by 5-ALA fluorescence in 21 consecutive patients with high-grade glioma and two neuronavigation-guided biopsies. Twenty-three patients underwent operations. Tumor volume and localization were quantified with pre- and postoperative volumetric MRI in non-biopsy cases. In non-biopsy cases, the age range was 20 to 79 years, with a median of 56 (interquartile range = 45-66). Histological analysis indicated that 14 had glioblastoma multiforme, 2 grade-III oligodendrogliomas and 1 anaplastic astrocytoma, 3 metastases and 1 low-grade astrocytoma. Total resection was achieved in 15 cases; subtotal resection was performed in 5 patients. The result was partial resection in one case. There was no perioperative mortality. The median fluorescence intensity, on a scale of 1-5, was 4.5 in the GBM group (IQR = 4-5), 3 (IQR = 2.5-3.5) in anaplastic glioma, and 2.5 (IQR = 2.25-2.75) for oligodendrogliomas. Of the three metastases, one showed fluorescence level 4. As for the two biopsy cases, one was anaplastic astrocytoma and one glioblastoma multiforme. The samples obtained were fluorescent in both cases. An exoscope can be also used for fluorescence-guided surgery with 5-aminolevulinic acid (5-ALA) and neuronavigation-guided biopsy. With an important advantage of low cost, this allows the surgeon to perform collaborative surgeries and adds agility to the procedure.

  19. CD47 activation-induced UHRF1 over-expression is associated with silencing of tumor suppressor gene p16INK4A in glioblastoma cells.

    Science.gov (United States)

    Boukhari, Abdelaziz; Alhosin, Mahmoud; Bronner, Christian; Sagini, Krizia; Truchot, Cécile; Sick, Emilie; Schini-Kerth, Valerie B; André, Philippe; Mély, Yves; Mousli, Marc; Gies, Jean-Pierre

    2015-01-01

    CD47, an integrin-associated protein is over-expressed in several tumors including glioblastomas. Activation of CD47 induces proliferation of human astrocytoma cells but not normal astrocytes via an Akt-dependent way. However, the pathways mediating this process are still unknown. The epigenetic integrator UHRF1 (Ubiquitin-like containing PHD and RING Finger 1) is over-expressed in various cancers and plays a vital role in the silencing of numerous tumor suppressor genes including p16(INK4A), thereby promoting cell proliferation. The aim of the present study was to investigate the role of UHRF1 and p16(INK4A) in CD47-induced effects. Herein we showed that activation of CD47 in human astrocytoma cell lines U87 and CCF- STTG1 (Grade IV), up-regulated the expression of UHRF1 with subsequent down-regulation of p16(INK4A), thus promoting cell proliferation. Blockage of CD47 using a blocking antibody down-regulated UHRF1 expression, accompanied by a re-expression of p16(INK4A), conducting to decreased cell proliferation in both cancer cell lines. Neither CD47 activation nor its blocking has any effect on UHRF1/p16(INK4A) expression in normal human astrocytes. Depletion of CD47 in the U87 cell line resulted in down-regulation of UHRF1. We also found that CD47 activated the inflammatory genes IL-6, IL-7 and MCP-1 by a NF-κB-dependent mechanism in human astrocytoma but not in normal astrocytes. In conclusion, the present findings indicate that CD47 activation increases expression of UHRF1 and suggest, for the first time, that CD47 regulates the epigenetic code by targeting UHRF1. This could represent a new pathway towards cell proliferation and metastasis. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  20. Analysis of p53- immunoreactivity in astrocytic brain tumors

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    Shinkarenko T.V.

    2016-12-01

    Full Text Available P53 is an antioncogene with the frequently occured mutations in human tumor cells, leading to corresponding protein overexpression which can be detected by immunohistochemistry. Researches dedicated to the investigation of possibilities of using this technique gave controversial results. The authors investigated features of p53 protein expression in astrocytic brain tumors with different degrees of malignancy. Analyzed the relationship of the expression level of p53 by tumor cells with clinical parameters and Ki-67 proliferation index (PI as well. Tissues were collected from 52 cases with diagnosed astrocytic brain tumors. The sections were immunohistochemically stained with p53 and Ki-67. For each marker, 1000 tumor cells were counted and the ratio of positive tumor cells was calculated using software package ImageJ 1,47v. In normal brain tissue p53- expression was not identified. p53-immunoreactive tumor cells were detected in 25% (1/4 pilocytic astrocytomas, 33.3% (2/6 of diffuse astrocytomas, 53.8% (7/13 anaplastic astrocytomas, 58.6% (17/29 glioblastomas. A high proportion of p53-immunoreactive cells (> 30% was observed only in glioblastomas. The level of p53-imunoreactivity was not related to the age, gender and Grade WHO (p> 0,05. Spearman correlation coefficient between the relative quantity of ki-67- and p53-immunoreactive nuclei showed weak direct correlation (0.023, but the one was not statistically significant (p> 0,05. The level of p53-imunoreactivity is not dependent from age and sex of patients, Grade (WHO and proliferative activity (p>0,05 but the high level of p53-immunoreactive cells (>30% is found in glioblastoma specimens only, that may be due to the accumulation of mutations in DNA of tumor cells. There is insignificant weak relationship between relative quantities of ki-67- and p53-immunoreactive tumor cells (p>0,05.

  1. Trends in childhood brain tumor incidence, 1973-2009.

    Science.gov (United States)

    McKean-Cowdin, Roberta; Razavi, Pedram; Barrington-Trimis, Jessica; Baldwin, Rachel Tobias; Asgharzadeh, Shahab; Cockburn, Myles; Tihan, Tarik; Preston-Martin, Susan

    2013-11-01

    In the mid-1980s, there was a rise in incidence rates of childhood brain tumors (CBT) in the United States that appeared to stabilize at a higher rate in the early 1990 s. An updated analysis of the pattern of CBT over the past 2 decades, with commentary on whether the elevated incidence rate has continued, is past due. We used Surveillance, Epidemiology and End Results (SEER) data to examine trends in incidence of CBT from 1973 through 2009. We examined age-adjusted incidence rates (AAIRs) and secular trends for all malignant brain tumors combined (SEER classification) by histologic tumor type and anatomic site. The incidence of CBT remained stable from 1987 to 2009 [annual percent change (APC) = 0.10; 95 % confidence intervals (CI) -0.39 to 0.61] with an AAIR for all CBT of 3.32 (95 % CI 3.22-3.42). The stability of rates in these two decades contrast the change that occurred in the mid-1980s (1983-1986), when the incidence of CBT increased by 53 % (APC = 14.06; 95 % CI 4.05-25.0). From 1983 to 1986, statistically significant rate increases were observed for pilocytic astrocytoma, PNET/medulloblastoma, and mixed glioma. Further, the rate of increase in pilocytic astrocytoma was similar to the rate of decrease for astrocytomas NOS from 1981 to 2009, suggesting a change from a more general to more specific classification. After the increase in rates in the mid-1980s, rates of CBT over the past two decades have stabilized. Changes in incidence rates of subtypes of tumors over this time period reflect changes both in classification of CBT and in diagnostic techniques.

  2. Neuroglial intramedullary tumors: The collaboration between neurosurgeons and neuropathologists.

    Science.gov (United States)

    Cossu, G; Lacroix, C; Adams, C; Daniel, R T; Parker, F; Messerer, M

    2017-11-01

    Intramedullary tumors constitute approximately 5% of spinal tumors and about 80% are of neuroglial origin. We reviewed our series of adult patients with spinal neuroglial intramedullary tumors operated on between 1984 and 2011 at the neurosurgical department of Bicêtre hospital. The histopathological records for 196 patients were retrospectively analyzed. The majority of tumors were ependymomas (68%) and astrocytomas (27.5%). The importance of a proper and detailed neuropathological diagnosis is the key to define patient management. The available literature data about the genetic profiles of these rare tumors are summarized and reviewed. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  3. Role of astrocytic leptin receptor subtypes on leptin permeation across hCMEC/D3 human brain endothelial cells

    OpenAIRE

    Hsuchou, Hung; Kastin, Abba J.; Tu, Hong; Abbott, N. Joan; Couraud, Pierre-Olivier; Pan, Weihong

    2010-01-01

    Astrocytic leptin receptors (ObR) can be upregulated in conditions such as adult-onset obesity. To determine whether the levels and subtypes of astrocytic ObR modulate leptin transport, we co-cultured hCMEC/D3 human brain endothelial cells and C6 astrocytoma cells in the Transwell system, and tested leptin permeation from apical to basolateral chambers. In comparison with hCMEC alone, co-culture of C6 cells reduced the permeability of paracellular markers and leptin. Unexpectedly, ObRb overex...

  4. Characterization of cells recovered from the xenotransplanted NG97 human-derived glioma cell line subcultured in a long-term in vitro

    Directory of Open Access Journals (Sweden)

    Heinrich Juliana K

    2008-10-01

    Full Text Available Abstract Background In order to elucidate tumoral progression and drug resistance, cultured cell lines are valuable tools applied on tumor related assays provided they are well established and characterized. Our laboratory settled the NG97 cell line derived from a human astrocytoma grade III, which started to develop and express important phenotypical characteristics of an astrocytoma grade IV after injection in the flank of nude mice. Astrocytomas are extremely aggressive malignancies of the Central Nervous System (CNS and account for 46% of all primary malignant brain tumors. Progression to worse prognosis occurs in 85% of the cases possibly due to changes in cell tumor microenvironment and through biological pathways that are still unclear. Methods This work focused on characterizing the NG97 cell line specifically after being recovered from the xenotransplant, who maintained their undifferentiated characteristics along the following 60th passages in vitro. These cells were subcultivated to evaluate the possible contribution of these undifferentiated characteristics to the malignant progression phenotype. These characteristics were the expression of molecules involved in the processes of migration, dedifferentiation and chromosomal instability. Results Results showed that NG97(ht had an decrease in doubling time through sub cultivation, which was characterized by a converse modulation between the expression of glial fibrillary acidic protein (GFAP and vimentin. In addition, β1 integrins were present in intermediate levels while α5 integrins had a high expression profile as well as fibronectin and laminin. Cytogenetic analysis of NG97(ht revealed several chromosomal abnormalities, 89% of the cells showed to be hyperdiploid and the modal number was assigned to be 63. Several acrocentric chromosomes were visualized and at least 30 figures were attributed to be murine. These findings suggest a possible fusion between the original NG97 cells

  5. CT and MR imaging of cerebral cavernous angiomas. Scanographie et IRM des angiomes caverneux cerebraux

    Energy Technology Data Exchange (ETDEWEB)

    Silbermann, O.; Dietemann, J.L.; Tajahmady, T.; Jeung, M.Y.; Granel de Solignac, M.; Vouge, M.; Badoz, A.; Dosch, J.C. (Centre Hospitalier Regional Universitaire 67 - Strasbourg (FR)) (and others); Froideveaux, J.C.; Kiesmann, M.

    1991-01-01

    Computed tomography, then MRI, have completely changed the diagnostic approach of cavernous hemangiomas. The CT image of these vascular malformations may still be misleading, as the lesion usually is naturally hyperdense and often enhances with an iodine injection; the differential diagnosis with low-grade astrocytoma or oligodendroglioma may be difficult. MRI produces a more characteristic image by demonstrating the peripheral rim of hemosiderin and the hemorrhagic sequellae in the center of the lesion. On T1- as well as T2-weighted images, the center of the lesion is hyperintense, while its periphery is hypointense.

  6. Hard Retinal exudates and visual loss due to papilledema

    Energy Technology Data Exchange (ETDEWEB)

    Rush, J.A.

    1982-02-01

    Bilateral papilledema developed in a patient with a cystic, grade 3 astrocytoma of the right frontal lobe. Despite successful neurosurgical treatment, /sup 60/Co radiotherapy, and oral corticosteroid therapy, progressive visual loss occurred. At examination one year later, visual activity was 20/200 and 20/70, and extensive lipid exudates in the peripapillary retina and central macula of each eye were noted. Retinal lipid exudates rarely complicate the course of surviving patients who had papilledema from intracranial tumor; physicians involved in the multispecialty care of such patients should be aware of the possible ocular residuals of persistent papilledema in an otherwise successfully treated patient.

  7. Molecular mechanisms in gliomagenesis

    DEFF Research Database (Denmark)

    Hulleman, Esther; Helin, Kristian

    2005-01-01

    , in order to design novel therapies and treatments for GBM, research has recently intensified to identify the cellular and molecular mechanisms leading to GBM formation. Modeling of astrocytomas by genetic manipulation of mice suggests that deregulation of the pathways that control gliogenesis during normal...... brain development, such as the differentiation of neural stem cells (NSCs) into astrocytes, might contribute to GBM formation. These pathways include growth factor-induced signal transduction routes and processes that control cell cycle progression, such as the p16-CDK4-RB and the ARF-MDM2-p53 pathways...

  8. Mutant Metabolic Enzymes Are at the Origin of Gliomas

    OpenAIRE

    Yan, Hai; Bigner, Darell D.; Velculescu, Victor; Parsons, D.Williams

    2009-01-01

    Mutations of the isocitrate dehydrogenase (IDH) metabolic enzymes IDH1 and IDH2 have been found to be frequent and early genetic alterations in astrocytomas and oligodendrogliomas. All mutations identified to date affect a single amino acid located within the isocitrate binding site (R132 of IDH1 and the analogous R172 residue of IDH2). IDH1 and IDH2 mutations define a specific subtype of gliomas and may have significant utility for the diagnosis, prognosis, and treatment of patients with the...

  9. Intracranial pathology of the visual pathway

    Energy Technology Data Exchange (ETDEWEB)

    Mueller-Forell, W. E-mail: mueller-forell@neuroradio.klinik.uni-mainz.de

    2004-02-01

    Intracranial pathologies involving the visual pathway are manifold. Aligning to anatomy, the most frequent and/or most important extrinsic and intrinsic intracranial lesions are presented. Clinical symptoms and imaging characteristics of lesions of the sellar region are demonstrated in different imaging modalities. The extrinsic lesions mainly consist of pituitary adenomas, meningeomas, craniopharyngeomas and chordomas. In (asymptomatic and symptomatic) aneurysms, different neurological symptoms depend on the location of aneurysms of the circle of Willis. Intrinsic tumors as astrocytoma of any grade, ependymoma and primary CNS-lymphoma require the main pathology in the course of the visual pathway. Vascular and demyelinating diseases complete this overview of intracranial lesions.

  10. Direct intratumoral application of radioactive substances (/sup 32/P-colloid) and chemotherapeutic agents (BCNU) as a multimodal treatment of brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Pannek, H.W.; Brock, M.; Franke, A.

    1987-12-01

    The multimodal approach to the treatment of inoperable gliomas is exemplified by the report of a case of astrocytoma IV (WHO). This ist the first application of a liquid nucleid (/sup 32/P) in combination with a chemotherapeutic substance (BCNU). This treatment was performed on a comatose patient who had already been given up, and who was suffering from a right-sided cystic temporal glioblastoma. An improvement of the life quality and of neurological symptoms over a period of 2 1/2 months resulted.

  11. Brain tumors in children; Hirntumoren beim Kind

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    Harting, I.; Seitz, A. [Universitaetsklinikum Heidelberg (Germany). Abt. Neuroradiologie

    2009-06-15

    Brain tumors are common in children; in Germany approximately 400 children are diagnosed every year. In the posterior fossa, cerebellar neoplasms outnumber brainstem gliomas. In contrast to their rarity in adults, brainstem gliomas are not uncommon in children. Supratentorial tumors can be subdivided by location into neoplasms of the cerebral hemispheres, suprasellar and pineal tumors. Astrocytoma is the most common pediatric brain tumor followed by medulloblastoma, ependymoma and craniopharyngeoma. The combination of imaging morphology, tumor localisation and patient age at manifestation form the basis of the neuroradiological differential diagnosis. (orig.)

  12. Stereological estimates of nuclear volume and other quantitative variables in supratentorial brain tumors. Practical technique and use in prognostic evaluation

    DEFF Research Database (Denmark)

    Sørensen, Flemming Brandt; Braendgaard, H; Chistiansen, A O

    1991-01-01

    the practical technique. The continuous variables were correlated with the subjective, qualitative WHO classification of brain tumors, and the prognostic value of the parameters was assessed. Well differentiated astrocytomas (n = 14) had smaller estimates of the volume-weighted mean nuclear volume and mean......p approximately 0.05, respectively). Age above the median and short duration of symptoms were significantly associated with short survival (2p = 0.01). Further investigations of larger series of patients are needed to define the clinical usefulness of these objective, reproducible, and quantitative...

  13. Histone H3.3 and cancer: A potential reader connection

    OpenAIRE

    Lan, Fei; Shi, Yang

    2014-01-01

    The building block of chromatin is nucleosome, which consists of 146 base pairs of DNA wrapped around a histone octamer composed of two copies of histone H2A, H2B, H3, and H4. Significantly, the somatic missense mutations of the histone H3 variant, H3.3, are associated with childhood and young-adult tumors, such as pediatric high-grade astrocytomas, as well as chondroblastoma and giant-cell tumors of the bone. The mechanisms by which these histone mutations cause cancer are by and large uncle...

  14. Carotid angiography

    Directory of Open Access Journals (Sweden)

    Arne Torkildsen

    1950-03-01

    Full Text Available After a brief review of the history of cerebral angiography, some of the most important points concerning the percutaneous angiographic technique have been described. The value of the angiographic examination in cases of cerebral gliomas has been studied, based upon a consecutive series of 127 verified cases of hemispherical gliomas. Of 31 cases of frontal glioma, 28 could be diagnosed by the angiographic method; of 33 cases of parietal glioma, the angiograms revealed the neoplasm in 27 instances; of 39 cases of temporal glioma, the tumor could be localized in 38 cases; of 13 cases of occipital glioma, the angiographic localization of the tumor was successfull in 9 instances; of 11. cases of glioma infiltrating the corpus callosum and (or the basal ganglia, the angiographic examination was successful in only 3 cases. The angiographic examination in cases of cerebral glioma, in my experience, yields a more satisfactory result as to the localization than does the pneumography. The only exception concerns the gliomas growing in the thalamus or in the basal ganglia. These are more easily localized by means of ventriculography. As to the differential diagnosis of the gliomas, tumor vessels could, be seen both in astrocytomas and in glioblastomas. Most cases of astrocytomas were however devoid of specific tumor vessels. When present they could not be definitely distinguished from those seen in glioblastomas, but the abnormal findings were far less numerous and definitely less pronounced in astrocytomas than in glioblastomas. In most cases the astrocytomas were characterized only by displacement of blood vessels of normal appearance, while the glioblastomas frequently-presented both displacement of normal appearing blood vessels and new formed blood vessels within the neoplasm itself. The pathological blood vessels in the tumor were frequently abnormal both regarding their topographical appearance and their type. Frequent findings were arterio

  15. A case of early-onset radiation retinopathy

    Energy Technology Data Exchange (ETDEWEB)

    Sato, Yoko; Den, Seika; Shimizu, Kazuhiro; Ikeda, Tsunehiko [Osaka Medical Coll., Takatsuki (Japan)

    2001-12-01

    We encountered a 27-year-old male early caused by radiation retinopathy five months after radiotherapy (51 Gy) for astrocytoma. The retinopathy was the proliferative retinopathy, with several dot and blot hemorrhages, hard and soft exudate, increased capillary permeability, macula edema and avasucular areas. So it was treated with panretial photocoagulation like diabetic retinopathy. Now hemorrhage, exudate, edema and avascular areas were improved. Photocoagulation treatment is effective to stop the progression of radiation retinopathy. Radiation retinopathy is sometimes early caused, therefore long-term follow up is recommended on starting radiotherapy. (author)

  16. Mucocutaneous complications of intraarterial 5-bromodeoxyuridine and radiation

    Energy Technology Data Exchange (ETDEWEB)

    McCuaig, C.C.; Ellis, C.N.; Greenberg, H.S.; Hegarty, T.J.; Page, M.A. (Univ. of Michigan Medical Center, Ann Arbor (USA))

    1989-12-01

    5-Bromodeoxyuridine (BUDR), a halopyrimidine thymidine analogue, is incorporated into the DNA of dividing cells and causes photoradiosensitization. Twenty-five patients with malignant astrocytomas were treated with continuous intracarotid BUDR radiosensitization and radiotherapy for 8 1/2 weeks. Unique dose-limiting mucocutaneous complications were encountered. Ipsilateral facial dermatitis with epilation of eyebrows and eyelashes, ocular irritation, and bilateral nail dystrophy developed in all patients. Less common reactions included oral ulceration in six patients, body exanthem on the trunk in five, and atypical erythema multiforme major in one.

  17. Reverse Engineering of Modified Genes by Bayesian Network Analysis Defines Molecular Determinants Critical to the Development of Glioblastoma

    Science.gov (United States)

    Kunkle, Brian W.; Yoo, Changwon; Roy, Deodutta

    2013-01-01

    In this study we have identified key genes that are critical in development of astrocytic tumors. Meta-analysis of microarray studies which compared normal tissue to astrocytoma revealed a set of 646 differentially expressed genes in the majority of astrocytoma. Reverse engineering of these 646 genes using Bayesian network analysis produced a gene network for each grade of astrocytoma (Grade I–IV), and ‘key genes’ within each grade were identified. Genes found to be most influential to development of the highest grade of astrocytoma, Glioblastoma multiforme were: COL4A1, EGFR, BTF3, MPP2, RAB31, CDK4, CD99, ANXA2, TOP2A, and SERBP1. All of these genes were up-regulated, except MPP2 (down regulated). These 10 genes were able to predict tumor status with 96–100% confidence when using logistic regression, cross validation, and the support vector machine analysis. Markov genes interact with NFkβ, ERK, MAPK, VEGF, growth hormone and collagen to produce a network whose top biological functions are cancer, neurological disease, and cellular movement. Three of the 10 genes - EGFR, COL4A1, and CDK4, in particular, seemed to be potential ‘hubs of activity’. Modified expression of these 10 Markov Blanket genes increases lifetime risk of developing glioblastoma compared to the normal population. The glioblastoma risk estimates were dramatically increased with joint effects of 4 or more than 4 Markov Blanket genes. Joint interaction effects of 4, 5, 6, 7, 8, 9 or 10 Markov Blanket genes produced 9, 13, 20.9, 26.7, 52.8, 53.2, 78.1 or 85.9%, respectively, increase in lifetime risk of developing glioblastoma compared to normal population. In summary, it appears that modified expression of several ‘key genes’ may be required for the development of glioblastoma. Further studies are needed to validate these ‘key genes’ as useful tools for early detection and novel therapeutic options for these tumors. PMID:23737970

  18. Maternal smoking during pregnancy and the risk of childhood brain tumors: Results from a Swedish cohort study.

    Science.gov (United States)

    Tettamanti, Giorgio; Ljung, Rickard; Mathiesen, Tiit; Schwartzbaum, Judith; Feychting, Maria

    2016-02-01

    Tobacco metabolites and carcinogens can be found in placental and umbilical cord tissues of fetuses exposed to maternal smoking. However, studies regarding maternal smoking during pregnancy and childhood brain tumor (CBT) have shown inconsistent results. All children born in Sweden between 1983 and 2010 and with information about maternal smoking during pregnancy, obtained from the Swedish Medical Birth Register, were included in this population based cohort study (n=2,577,305). CBT cases were identified from the National Cancer Register. Cox regression models were used to estimate the effect of maternal smoking during pregnancy on the risk of CBTs. We identified 1039 cases of CBT in the cohort. Overall, there was little or no effect of maternal smoking during pregnancy on the risk of CBTs. However, in analyses stratified by age at diagnosis and child's sex, positive associations were found among 5-9 years old children. In this age interval, maternal smoking during pregnancy was associated with an increased risk of all CBTs combined only among male children (RR=1.50, 95% CI 0.96-2.34), while for astrocytoma there was a positive association in both male (RR=2.00, 95% CI 1.02-3.91) and female children (RR=1.80, 95% CI 0.85-3.82). Results from this large Swedish cohort study suggest that even though maternal smoking during pregnancy has a limited overall effect on CBTs, it may increase the risk of astrocytomas. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Malignant Transformation in Glioma Steered by an Angiogenic Switch: Defining a Role for Bone Marrow-Derived Cells.

    Science.gov (United States)

    Xu, Raymond; Pisapia, David; Greenfield, Jeffrey P

    2016-01-27

    Low-grade gliomas, such as pilocytic astrocytoma and subependymoma, are often characterized as benign tumors due to their relative circumscription radiologically and typically non-aggressive biologic behavior. In contrast, low-grades that are by their nature diffusely infiltrative, such as diffuse astrocytomas and oligodendrogliomas, have the potential to transform into malignant high-grade counterparts and, given sufficient time, invariably do so. These high-grade gliomas carry very poor prognoses and are largely incurable, warranting a closer look at what causes this adverse transition. A key characteristic that distinguishes low- and high-grade gliomas is neovascularization: it is absent in low-grade gliomas, but prolific in high-grade gliomas, providing the tumor with ample blood supply for exponential growth. It has been well described in the literature that bone marrow-derived cells (BMDCs) may contribute to the angiogenic switch that is responsible for malignant transformation of low-grade gliomas. In this review, we will summarize the current literature on BMDCs and their known contribution to angiogenesis-associated tumor growth in gliomas.

  20. Isolated third ventricle glioblastoma.

    Science.gov (United States)

    Yılmaz, Baran; Ekşi, Murat Şakir; Demir, Mustafa Kemal; Akakın, Akın; Toktaş, Zafer Orkun; Yapıcıer, Özlem; Kılıç, Türker

    2016-01-01

    Glioblastoma is the most common and the most malignant type of gliomas. Cerebral hemispheres are usual locations for gliomas. Isolated third ventricular presentation is very rare for glioblastomas. A new case of isolated third ventricular glioblastoma has been presented in this report. A 36-year-old woman was admitted to outpatient clinic with headache, blurred vision and confusion. A head CT scan and MRI had showed third ventricular mass lesion with obstructive hydrocephalus. Previous to her admission to our clinic, a ventriculo-peritoneal shunt had been inserted and her hydrocephalus had been relieved to some extent in acute settings. In our clinic, stereotactic biopsy was performed and a second ventriculoperitoneal shunt was inserted from the opposite site. Histopathological diagnosis was glioblastoma. Radiotherapy and chemotherapy were started immediately after the surgery. Patient's hydrocephalus has resolved and she was well at post-operative 6th month. In differential diagnosis list of the tumors presenting in the third ventricle, there are plenty of tumors such as colloid cyst, meningioma, germinoma, craniopharyngioma, lymphoma, choroid plexus papilloma, subependymal giant cell astrocytoma, chiasmatic and hypothalamic benign astrocytoma. Ring enhancement of this region pathology is a peculiar sign for glioblastoma, yet not pathognomonic. Tumor histology is crucial to yield the final diagnosis. Management of obstructive hydrocephalus, making histopathological diagnosis, starting adjuvant radiotherapy and chemotherapy in isolated third ventricular glioblastomas is a safe and effective approach when we consider malignant nature and intractable progress of glioblastomas.

  1. Genetic Alterations in Gliosarcoma and Giant Cell Glioblastoma.

    Science.gov (United States)

    Oh, Ji Eun; Ohta, Takashi; Nonoguchi, Naosuke; Satomi, Kaishi; Capper, David; Pierscianek, Daniela; Sure, Ulrich; Vital, Anne; Paulus, Werner; Mittelbronn, Michel; Antonelli, Manila; Kleihues, Paul; Giangaspero, Felice; Ohgaki, Hiroko

    2016-07-01

    The majority of glioblastomas develop rapidly with a short clinical history (primary glioblastoma IDH wild-type), whereas secondary glioblastomas progress from diffuse astrocytoma or anaplastic astrocytoma. IDH mutations are the genetic hallmark of secondary glioblastomas. Gliosarcomas and giant cell glioblastomas are rare histological glioblastoma variants, which usually develop rapidly. We determined the genetic patterns of 36 gliosarcomas and 19 giant cell glioblastomas. IDH1 and IDH2 mutations were absent in all 36 gliosarcomas and in 18 of 19 giant cell glioblastomas analyzed, indicating that they are histological variants of primary glioblastoma. Furthermore, LOH 10q (88%) and TERT promoter mutations (83%) were frequent in gliosarcomas. Copy number profiling using the 450k methylome array in 5 gliosarcomas revealed CDKN2A homozygous deletion (3 cases), trisomy chromosome 7 (2 cases), and monosomy chromosome 10 (2 cases). Giant cell glioblastomas had LOH 10q in 50% and LOH 19q in 42% of cases. ATRX loss was detected immunohistochemically in 19% of giant cell glioblastomas, but absent in 17 gliosarcomas. These and previous results suggest that gliosarcomas are a variant of, and genetically similar to, primary glioblastomas, except for a lack of EGFR amplification, while giant cell glioblastoma occupies a hybrid position between primary and secondary glioblastomas. © 2015 International Society of Neuropathology.

  2. MRI of high-grade astrocytic tumors: early appearance and evolution

    Energy Technology Data Exchange (ETDEWEB)

    Okamoto, K.; Takahashi, N.; Ishikawa, K.; Furusawa, T.; Sakai, K. [Department of Radiology, Niigata University Faculty of Medicine (Japan); Ito, J.; Tokiguchi, S. [Department of Radiology, Niigata University Faculty of Dentistry (Japan)

    2002-05-01

    The clinical management and prognosis of patients with diffusely infiltrating astrocytomas are dependent on neuropathological grading of the tumors. The characteristics of MR images of high-grade astrocytic tumors are well known, but the early MRI appearance and the MRI evolution of high-grade astrocytic tumors have rarely been examined. We retrospectively reviewed MR images obtained from 4 months to 3 years and 3 months before admission, as well as MR images on admission, for five patients with pathologically proven high-grade astrocytic tumors (two glioblastomas and three anaplastic astrocytomas). In two patients, neoplastic lesions were not detectable on initial MRI, even retrospectively. In the remaining three patients, however, hyperintense areas with little or no mass effect were demonstrated on T2-weighted imaging. These lesions were misinterpreted as non-neoplastic processes, such as ischemic lesion or infarction, or demyelinating processes. All tumors showed gadolinium enhancement on admission, that emerged from the previously existing hyperintense areas on T2-weighted images without gadolinium enhancement, except for one de novo glioblastoma. Development of a small central cyst without gadolinium enhancement was demonstrated in one case before the emergence of an enhancing area. (orig.)

  3. How specific is the MRI appearance of supratentorial atypical teratoid rhabdoid tumors?

    Energy Technology Data Exchange (ETDEWEB)

    Au Yong, Kong Jung; Jaremko, Jacob L.; Bhargava, Ravi [University of Alberta Hospital, Department of Radiology and Diagnostic Imaging, Edmonton (Canada); Jans, Lennart [Ghent University Hospital, Department of Radiology and Medical Imaging, Gent (Belgium); Coleman, Lee T. [University of Melbourne and Murdoch Children' s Research Institute, Department of Radiology and Pediatrics, Melbourne (Australia); Medical Imaging, Royal Children' s Hospital, Parkville (Australia); Mehta, Vivek [University of Alberta Hospital, Department of Neurosurgery, Edmonton (Canada); Ditchfield, Michael R. [Monash Children' s and Monash University, Monash Medical Centre, Diagnostic Imaging, Clayton (Australia)

    2013-03-15

    Supratentorial atypical teratoid rhabdoid tumor (ATRT) in many cases has a distinctive appearance on post-gadolinium MRI. We sought to determine whether this is a unique appearance allowing ATRT to be distinguished accurately from other types of pediatric supratentorial tumors. Retrospective review of all available preoperative MRI of pediatric supratentorial tumors at two tertiary children's hospitals, and systematic literature review of case series and reports describing the MRI imaging appearances of supratentorial ATRT. We had 61 supratentorial tumors, including 32 gliomas, 6 ATRT, 8 ependymomas, 6 gangliogliomas, 2 pilomyxoid astrocytomas, 3 primitive neuro-ectodermal tumors, 2 choroid plexus papillomas, and 2 meningiomas. ATRT presented in significantly younger patients than astrocytomas (mean age 2.6 years vs. 9.9 years, P < 0.05). The visual pattern of a thick, wavy (irregular) heterogeneously enhancing wall around a cystic center was seen in 5/6 (83%) ATRTs and only 3/55 (5.4%) other tumors (P < 0.0001), for specificity of 95%, sensitivity of 83%, positive predictive value of 63% and a negative predictive value of 95%. A supratentorial tumor with a thick, wavy (irregular) heterogeneously enhancing wall surrounding a central cystic region is suggestive of ATRT in the appropriate clinical setting, especially in a child of preschool age. (orig.)

  4. Proliferative and Invasive Effects of Progesterone-Induced Blocking Factor in Human Glioblastoma Cells

    Directory of Open Access Journals (Sweden)

    Araceli Gutiérrez-Rodríguez

    2017-01-01

    Full Text Available Progesterone-induced blocking factor (PIBF is a progesterone (P4 regulated protein expressed in different types of high proliferative cells including astrocytomas, the most frequent and aggressive brain tumors. It has been shown that PIBF increases the number of human astrocytoma cells. In this work, we evaluated PIBF regulation by P4 and the effects of PIBF on proliferation, migration, and invasion of U87 and U251 cells, both derived from human glioblastomas. PIBF mRNA expression was upregulated by P4 (10 nM from 12 to 24 h. Glioblastoma cells expressed two PIBF isoforms, 90 and 57 kDa. The content of the shorter isoform was increased by P4 at 24 h, while progesterone receptor antagonist RU486 (10 μM blocked this effect. PIBF (100 ng/mL increased the number of U87 cells on days 4 and 5 of treatment and induced cell proliferation on day 4. Wound-healing assays showed that PIBF increased the migration of U87 (12–48 h and U251 (24 and 48 h cells. Transwell invasion assays showed that PIBF augmented the number of invasive cells in both cell lines at 24 h. These data suggest that PIBF promotes proliferation, migration, and invasion of human glioblastoma cells.

  5. Imaging feature of infratentorial desmoplastic infantile and non-infantile tumors

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyun Gi; Lee, Seung Koo [Dept. of Radiology and Research Institute of Radiological Science, Severance Children' s Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Kim, Se Hoon [Dept. of Pathology, Yonsei University College of Medicine, Severance Hospital, Seoul (Korea, Republic of)

    2016-07-15

    To describe imaging features of infratentorial desmoplastic infantile or non-infantile tumors (DIT/DNIT). Four cases with infratentorial DIT/DNIT from our hospital and 5 cases from literature review were analyzed. Clinical data and MR imaging features were evaluated including location, size, shape, margin, composition, dural attachment, perilesional edema, and metastasis or multiplicity. The mean age was 9.2 years (range, 1-18 years). Most of the patients presented with headache or vomiting (4/9, 44.4%) and had no underlying disease (8/9, 88.9%). The major pathologic subtype was astrocytoma (6/9, 66.7%). On MR, majority of the tumors involved cerebellum and/or spinal cord (8/9, 88.9%) and the mean size of the tumors was 4.2 cm (range, 3.2-5 cm). The tumors were mainly solid (4/9, 44.4%) or mixed (4/9, 44.4%) in composition with lobulated shape (7/9, 77.8%) and well-defined margin (7/9, 77.8%). Two cases (2/7, 28.6%) showed dural attachment and all the cases had no or minimal perilesional edema (100%). Metastasis or multiplicity was frequently seen in 44.4% (4/9). Infratentorial DIT/DNIT occurred in relatively older children and the major tumor type was astrocytoma. They also had atypical imaging features showing mainly solid or mixed in composition with frequent metastasis or multiplicity.

  6. Right hemispheric frontal lesions as a cause for anorexia nervosa report of three cases.

    Science.gov (United States)

    Trummer, M; Eustacchio, S; Unger, F; Tillich, M; Flaschka, G

    2002-08-01

    Aetiology and pathogenesis of eating disorders is a matter of controversy. In some cases they can occur in association with tumours involving the temporal cortex, in temporal lobe epilepsy or in the advanced state of degenerative diseases involving temporal structures. We report about three patients with right frontal intracerebral lesions, one oligo-astrocytoma and two vascular malformations, associated with partial seizures and anorexia nervosa. 3 patients, one female and two men with anorexia nervosa and right frontal intracerebral lesions were admitted to our wards due to focal seizures or loss of consciousness. They were treated either microsurgically or by endovascular embolization after neuro-imaging. In our retrospective analysis of the patients' reports and course we investigated the histopathology of the lesions, duration of the eating disorder and the clinical outcome. Two patients underwent craniotomy with extirpation of the lesion. In one case histology revealed an oligo-astrocytoma, in the other haemorrhagic infarction due to a venous malformation. The patient with the arteriovenous malformation (AVM) was embolized with microparticles. The patients with the oligoastrocytoma and AVM totally recovered. They gained weight and stayed seizure free. The patient with the infarction remained in a vegetative state. Right frontal intracerebral lesions with their close relationship to the limbic system could be causative for eating disorders. We therefore recommend performing a cranial MRI in all patients with suspected eating disorders, especially if they occur in combination with focal seizures.

  7. Paradoxical perfusion metrics of high-grade gliomas with an oligodendroglioma component: quantitative analysis of dynamic susceptibility contrast perfusion MR imaging

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    Sunwoo, Leonard; Park, Sun-Won [Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Seoul Metropolitan Government - Seoul National University Boramae Medical Center, Department of Radiology, Seoul (Korea, Republic of); Choi, Seung Hong [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Seoul National University, Center for Nanoparticle Research, Institute for Basic Science, and School of Chemical and Biological Engineering, Seoul (Korea, Republic of); Yoo, Roh-Eul; Kang, Koung Mi; Yun, Tae Jin; Kim, Ji-hoon; Sohn, Chul-Ho [Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Kim, Tae Min; Lee, Se-Hoon [Seoul National University Hospital, Department of Internal Medicine, Seoul (Korea, Republic of); Park, Chul-Kee [Seoul National University Hospital, Department of Neurosurgery, Seoul (Korea, Republic of); Won, Jae-Kyung; Park, Sung-Hye [Seoul National University Hospital, Department of Pathology, Seoul (Korea, Republic of); Kim, Il Han [Seoul National University Hospital, Department of Radiation Oncology, Seoul (Korea, Republic of)

    2015-11-15

    The aim of this study is to investigate perfusion characteristics of glioblastoma with an oligodendroglioma component (GBMO) compared with conventional glioblastoma (GBM) using dynamic susceptibility contrast (DSC) perfusion magnetic resonance (MR) imaging and microvessel density (MVD). The study was approved by the institutional review board. Newly diagnosed high-grade glioma patients were enrolled (n = 72; 20 GBMs, 14 GBMOs, 19 anaplastic astrocytomas (AAs), 13 anaplastic oligodendrogliomas (AOs), and six anaplastic oligoastrocytomas (AOAs)). All participants underwent preoperative MR imaging including DSC perfusion MR imaging. Normalized cerebral blood volume (nCBV) values were analyzed using a histogram approach. Histogram parameters were subsequently compared across each tumor subtype and grade. MVD was quantified by immunohistochemistry staining and correlated with perfusion parameters. Progression-free survival (PFS) was assessed according to the tumor subtype. GBMO displayed significantly reduced nCBV values compared with GBM, whereas grade III tumors with oligodendroglial components (AO and AOA) exhibited significantly increased nCBV values compared with AA (p < 0.001). MVD analyses revealed the same pattern as nCBV results. In addition, a positive correlation between MVD and nCBV values was noted (r = 0.633, p < 0.001). Patients with oligodendroglial tumors exhibited significantly increased PFS compared with patients with pure astrocytomas in each grade. In contrast to grade III tumors, the presence of oligodendroglial components in grade IV tumors resulted in paradoxically reduced perfusion metrics and MVD. In addition, patients with GBMO exhibited a better clinical outcome compared with patients with GBM. (orig.)

  8. A Novel Molecular Diagnostic of Glioblastomas: Detection of an Extracellular Fragment of Protein Tyrosine Phosphatase μ

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    Susan M. Burden-Gulley

    2010-04-01

    Full Text Available We recently found that normal human brain and low-grade astrocytomas express the receptor protein tyrosine phosphatase mu (PTPμ and that the more invasive astrocytomas, glioblastoma multiforme (GBM, downregulate full-length PTPμ expression. Loss of PTPμ expression in GBMs is due to proteolytic cleavage that generates an intracellular and potentially a cleaved and released extracellular fragment of PTPμ. Here, we identify that a cleaved extracellular fragment containing the domains required for PTPμ-mediated adhesion remains associated with GBM tumor tissue. We hypothesized that detection of this fragment would make an excellent diagnostic tool for the localization of tumor tissue within the brain. To this end, we generated a series of fluorescently tagged peptide probes that bind the PTPμ fragment. The peptide probes specifically recognize GBM cells in tissue sections of surgically resected human tumors. To test whether the peptide probes are able to detect GBM tumors in vivo, the PTPμ peptide probes were tested in both mouse flank and intracranial xenograft human glioblastoma tumor model systems. The glial tumors were molecularly labeled with the PTPμ peptide probes within minutes of tail vein injection using the Maestro FLEX In Vivo Imaging System. The label was stable for at least 3 hours. Together, these results indicate that peptide recognition of the PTPμ extracellular fragment provides a novel molecular diagnostic tool for detection of human glioblastomas. Such a tool has clear translational applications and may lead to improved surgical resections and prognosis for patients with this devastating disease.

  9. Pathology, molecular genetics and epigenetics of diffuse intrinsic pontine glioma

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    Pawel eBuczkowicz

    2015-06-01

    Full Text Available Diffuse intrinsic pontine glioma (DIPG is a devastating pediatric brain cancer with no effective therapy. Histological similarity of DIPG to supratentorial high-grade astrocytomas of adults has led to assumptions that these entities possess similar underlying molecular properties and therefore similar therapeutic responses to standard therapies. The failure of all clinical trials in the last 30 years to improve DIPG patient outcome has suggested otherwise. Recent studies employing next-generation sequencing and microarray technologies have provided a breadth of evidence highlighting the unique molecular genetics and epigenetics of this cancer, distinguishing it from both adult and pediatric cerebral high-grade astrocytomas. This review describes the most common molecular genetic and epigenetic signatures of DIPG in the context of molecular subgroups and histopathological diagnosis, including this tumor entity’s unique mutational landscape, copy number alterations and structural variants as well as epigenetic changes on the global DNA and histone levels. The increased knowledge of DIPG biology and histopathology has opened doors to new diagnostic and therapeutic avenues.

  10. Imaging of Brain Tumors with Copper-64 Chloride: Early Experience and Results.

    Science.gov (United States)

    Panichelli, Paola; Villano, Carlo; Cistaro, Angelina; Bruno, Andrea; Barbato, Francesco; Piccardo, Arnoldo; Duatti, Adriano

    2016-06-01

    To conduct the first investigational study that is aimed at evaluating the ability of the simple salt (64)CuCl2 to diagnose cerebral tumors in patients affected by glioblastoma multiforme (GBM). Nineteen patients with a documented history and radiologic evidence of brain tumors were enrolled in the study. Eighteen patients were diagnosed with GBM, and one patient was diagnosed with grade II astrocytoma. After initial cerebral magnetic resonance imaging (MRI), patients were administered with (64)CuCl2 (13 MBq/kg) and brain positron emission tomography (PET)/computed tomography (CT) imaging was performed at 1, 3, and 24 hours after administration. Standardized uptake values (SUVs) were calculated and used to figure out the pharmacokinetic profile of the tracer. Absorbed radiation doses were estimated using OLINDA/EXM. Copper-64 chloride clearly visualized brain cancerous lesions within 1 hour after injection, with stable retention of radioactivity at 3 and 24 hours. Excellent agreement was found between PET/CT and MRI. No uptake of the tracer was observed in low-grade astrocytoma. The agent cleared rapidly from the blood and was mostly excreted through the liver, without significant kidney washout. Analysis of time variation of SUVmax values showed persistent uptake in malignant tissues with a slight increase of radioactive concentration at 24 hours. Copper-64 chloride has favorable biological properties for brain imaging and warrants further investigation as a diagnostic tracer for GBM.

  11. Serum alpha 2-HS glycoprotein predicts survival in patients with glioblastoma.

    Science.gov (United States)

    Petrik, Vladimir; Saadoun, Samira; Loosemore, Alison; Hobbs, Josie; Opstad, Kirstie S; Sheldon, Joanna; Tarelli, Edward; Howe, Franklyn A; Bell, B Anthony; Papadopoulos, Marios C

    2008-04-01

    Glioblastoma, the most common primary brain tumor, has variable prognosis. We aimed to identify serum biomarkers that predict survival of patients with glioblastoma. In phase 1 (biomarker discovery), SELDI-TOF mass spectra were studied in 200 serum samples from 58 control subjects and 36 patients with grade II astrocytoma, 15 with anaplastic astrocytoma, and 91 with glioblastoma. To identify potential biomarkers, we searched for peptide peaks that changed progressively in size with increasing malignancy. One peak, identified as the B-chain of alpha 2-Heremans-Schmid glycoprotein (AHSG), was less prominent with increasing tumor grade. We therefore investigated AHSG as a survival predictor in glioblastoma. We measured serum AHSG by turbidimetry and determined indices of malignancy, including tumor proliferation (Ki67 immunolabel) and necrosis (tumor lipids on magnetic resonance spectroscopy). In phase 2 (biomarker validation), the prognostic power of AHSG was validated in an independent group of 72 glioblastoma patients. Median survival was longer (51 vs 29 weeks) in glioblastoma patients with normal vs low serum AHSG concentrations (hazard ratio 2.7, 95% CI 1.5-5.0, P AHSG inversely correlated with Ki-67 immunolabeling and tumor lipids. A prognostic index combining serum AHSG with patient age and Karnofsky score separated glioblastoma patients with short (2 years) median survival. The prognostic value of serum AHSG was validated in a different cohort of glioblastoma patients. We conclude that serum AHSG concentration, measured before starting treatment, predicts survival in patients with glioblastoma.

  12. Gene Expression Analysis of an EGFR Indirectly Related Pathway Identified PTEN and MMP9 as Reliable Diagnostic Markers for Human Glial Tumor Specimens

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    Sergio Comincini

    2009-01-01

    Full Text Available In this study the mRNA levels of five EGFR indirectly related genes, EGFR, HB-EGF, ADAM17, PTEN, and MMP9, have been assessed by Real-time PCR in a panel of 37 glioblastoma multiforme specimens and in 5 normal brain samples; as a result, in glioblastoma, ADAM17 and PTEN expression was significantly lower than in normal brain samples, and, in particular, a statistically significant inverse correlation was found between PTEN and MMP9 mRNA levels. To verify if this correlation was conserved in gliomas, PTEN and MMP9 expression was further investigated in an additional panel of 16 anaplastic astrocytoma specimens and, in parallel, in different human normal and astrocytic tumor cell lines. In anaplastic astrocytomas PTEN expression was significantly higher than in glioblastoma multiforme, but no significant correlation was found between PTEN and MMP9 expression. PTEN and MMP9 mRNA levels were also employed to identify subgroups of specimens within the different glioma malignancy grades and to define a gene expression-based diagnostic classification scheme. In conclusion, this gene expression survey highlighted that the combined measurement of PTEN and MMP9 transcripts might represent a novel reliable tool for the differential diagnosis of high-grade gliomas, and it also suggested a functional link involving these genes in glial tumors.

  13. Cerebral glial tumors and human immunodeficiency virus-1 infection. More than a coincidental association.

    Science.gov (United States)

    Moulignier, A; Mikol, J; Pialoux, G; Eliaszewicz, M; Thurel, C; Thiebaut, J B

    1994-07-15

    The authors describe the clinical and morphologic patterns in four patients with acquired immune deficiency syndrome (AIDS) who developed intracranial glial tumors. This retrospective study reports 70 patients at various stages of human immunodeficiency virus-1 (HIV-1) infection who underwent stereotactic brain biopsy for an intracerebral space-occupying lesion. Of these patients, four had glial tumors: one astroblastoma, two astrocytomas, and one glioblastoma. Glial tumors probably arise from a complex interplay of factors; possibilities include the activation of a dominant oncogene or viral inactivation of a tumor suppressor gene by a viral promoter (like the tat protein), impairment of immune defenses (which facilitates the growth of astrocytomas in acute lymphoblastic leukemia), production of cellular growth factors, cytokines, possible infection of glial cells by HIV, and the potentiation of a coinfectious agent. These cases illustrate that glial tumors should be considered in the differential diagnosis of brain masses in HIV-1 infection, especially because specific treatment for these tumors is available. Moreover, the occurrence of glial tumors in AIDS patients is not only an important event from a clinical point of view, but may also have implications for the pathogenesis of tumors in AIDS.

  14. Neurofibromatosis type 1: brain stem tumours

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    Bilaniuk, L.T. [Department of Radiology, The Children`s Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, PA (United States); Molloy, P.T. [Division of Neurology, Children`s Hospital of Philadelphia, PA (United States); Zimmerman, R.A. [Department of Radiology, The Children`s Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, PA (United States); Phillips, P.C. [Division of Neurology, Children`s Hospital of Philadelphia, PA (United States); Vaughan, S.N. [Division of Neurology, Children`s Hospital of Philadelphia, PA (United States); Liu, G.T. [Division of Neuro-Ophthalmology, Children`s Hospital of Philadelphia, PA (United States); Sutton, L.N. [Division of Neurosurgery, Children`s Hospital of Philadelphia, PA (United States); Needle, M. [Division of Oncology, The Children`s Hospital of Philadelphia. PA (United States)

    1997-09-01

    We describe the clinical and imaging findings of brain stem tumours in patients with neurofibromatosis type 1 (NF1). The NF1 patients imaged between January 1984 and January 1996 were reviewed and 25 patients were identified with a brain stem tumour. Clinical, radiographical and pathological results were obtained by review of records and images. Brain stem tumour identification occurred much later than the clinical diagnosis of NF1. Medullary enlargement was most frequent (68 %), followed by pontine (52 %) and midbrain enlargement (44 %). Patients were further subdivided into those with diffuse (12 patients) and those with focal (13 patients) tumours. Treatment for hydrocephalus was required in 67 % of the first group and only 15 % of the second group. Surgery was performed in four patients and revealed fibrillary astrocytomas, one of which progressed to an anaplastic astrocytoma. In 40 % of patients both brain stem and optic pathway tumours were present. The biological behaviour of brain stem tumours in NF1 is unknown. Diffuse tumours in the patients with NF1 appear to have a much more favourable prognosis than patients with similar tumours without neurofibromatosis type 1. (orig.). With 7 figs., 3 tabs.

  15. Lipoprotein internalisation induced by oncogenic AMPK activation is essential to maintain glioblastoma cell growth.

    Science.gov (United States)

    Ríos, M; Foretz, M; Viollet, B; Prieto, A; Fraga, M; García-Caballero, T; Costoya, J A; Señarís, R

    2014-12-01

    Metabolic adaptations are essential during tumour growth to maintain the high proliferation levels exhibited by cancer cells. In this study, we examined the transformations that occurred in the lipid metabolism in astrocytic tumours, and the possible role of the fuel-sensing enzyme AMPK. Metabolic targets might help design new and effective drugs for cancer. To accomplish this objective, we studied both mice and human astrocytic tumours. We first used a mouse model of astrocytoma driven by oncogenic H-RasV12 and/or with PTEN deletion based on the common constitutive activation of the Raf/MEK/ERK and PI3K/AKT cascades in human astrocytomas. We then confirmed the results in human glioblastoma cell lines and in glioblastoma tissue samples from patients. We show that the high levels of activated AMPK, observed in astrocytic tumours, increase extracellular lipid internalisation and reduce energy expenditure by inhibiting 'de novo' fatty acid (FA) synthesis, which allows tumour cells to obtain building blocks and energy to be able to create new organelles and new cells. Our findings demonstrate that AMPK plays a crucial role in glioblastoma cell growth and suggest that blocking lipoprotein receptors could potentially be used as a plausible therapeutic approach for these and other type of tumours with high levels of AMPK. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. The molecular biology of WHO grade II gliomas.

    Science.gov (United States)

    Marko, Nicholas F; Weil, Robert J

    2013-02-01

    The WHO grading scheme for glial neoplasms assigns Grade II to 5 distinct tumors of astrocytic or oligodendroglial lineage: diffuse astrocytoma, oligodendroglioma, oligoastrocytoma, pleomorphic xanthoastrocytoma, and pilomyxoid astrocytoma. Although commonly referred to collectively as among the "low-grade gliomas," these 5 tumors represent molecularly and clinically unique entities. Each is the subject of active basic research aimed at developing a more complete understanding of its molecular biology, and the pace of such research continues to accelerate. Additionally, because managing and predicting the course of these tumors has historically proven challenging, translational research regarding Grade II gliomas continues in the hopes of identifying novel molecular features that can better inform diagnostic, prognostic, and therapeutic strategies. Unfortunately, the basic and translational literature regarding the molecular biology of WHO Grade II gliomas remains nebulous. The authors' goal for this review was to present a comprehensive discussion of current knowledge regarding the molecular characteristics of these 5 WHO Grade II tumors on the chromosomal, genomic, and epigenomic levels. Additionally, they discuss the emerging evidence suggesting molecular differences between adult and pediatric Grade II gliomas. Finally, they present an overview of current strategies for using molecular data to classify low-grade gliomas into clinically relevant categories based on tumor biology.

  17. Decreasing expression of the interleukin-13 receptor IL-13Ralpha2 in treated recurrent malignant gliomas.

    Science.gov (United States)

    Bozinov, Oliver; Kalk, Jens-Martin; Krayenbühl, Niklaus; Woernle, Christoph Michael; Sure, Ulrich; Bertalanffy, Helmut

    2010-01-01

    The IL-13Ralpha2 gene encodes for a 65 kDa protein that forms one of the subunits of the interleukin-13 (IL-13) receptor. This gene is highly expressed in various types of human tumors including malignant gliomas. The expression level of IL-13Ralpha2 was examined in a total of 45 tissue samples of anaplastic astrocytomas (AAs) World Health Organization (WHO) grade III, glioblastomas (GBMs) WHO grade IV, and first-recurrent glioblastomas (frGBMs) after treatment with radiation and chemotherapy. IL-13Ralpha2 expression was detected by semiquantitative reverse transcription real-time polymerase chain reaction (PCR) using ABI PRISM 7700 and Qiagen QuantiTect SYBR Green PCR kits. The expression level of IL-13Ralpha2 (15 fold) was significantly reduced in frGBMs compared to the primary GBMs (p = 0.014), and significantly reduced by more than 15 fold (p = 0.003) in all untreated malignant astrocytomas (AAs and GBMs) compared with treated frGBMs. Expression of IL-13Ralpha2 seems to be lower in frGBMs compared to GBMs. The promising antitumor effect of IL-13 cytotoxin could be greatly reduced in frGBM or only achievable with higher amounts of cytotoxin, due to the significantly lower expression of the cytotoxin's target structure.

  18. Chromosomal Aberrations in Canine Gliomas Define Candidate Genes and Common Pathways in Dogs and Humans.

    Science.gov (United States)

    Dickinson, Peter J; York, Dan; Higgins, Robert J; LeCouteur, Richard A; Joshi, Nikhil; Bannasch, Danika

    2016-07-01

    Spontaneous gliomas in dogs occur at a frequency similar to that in humans and may provide a translational model for therapeutic development and comparative biological investigations. Copy number alterations in 38 canine gliomas, including diffuse astrocytomas, glioblastomas, oligodendrogliomas, and mixed oligoastrocytomas, were defined using an Illumina 170K single nucleotide polymorphism array. Highly recurrent alterations were seen in up to 85% of some tumor types, most notably involving chromosomes 13, 22, and 38, and gliomas clustered into 2 major groups consisting of high-grade IV astrocytomas, or oligodendrogliomas and other tumors. Tumor types were characterized by specific broad and focal chromosomal events including focal loss of the INK4A/B locus in glioblastoma and loss of the RB1 gene and amplification of the PDGFRA gene in oligodendrogliomas. Genes associated with the 3 critical pathways in human high-grade gliomas (TP53, RB1, and RTK/RAS/PI3K) were frequently associated with canine aberrations. Analysis of oligodendrogliomas revealed regions of chromosomal losses syntenic to human 1p involving tumor suppressor genes, such as CDKN2C, as well as genes associated with apoptosis, autophagy, and response to chemotherapy and radiation. Analysis of high frequency chromosomal aberrations with respect to human orthologues may provide insight into both novel and common pathways in gliomagenesis and response to therapy. © 2016 American Association of Neuropathologists, Inc. All rights reserved.

  19. Expressão das proteínas BCL-2 e BAX em tumores astrocíticos humanos Expression of BCL-2 and BAX proteins in human astrocytic tumors

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    Mário Henrique Girão Faria

    2006-08-01

    Full Text Available INTRODUÇÃO: Os astrocitomas constituem os mais freqüentes tumores primários do sistema nervoso central (SNC. Admite-se que parte do crescimento tumoral seja resultante da inibição da morte celular programada: a apoptose. Tal fenômeno é basicamente regulado pelo equilíbrio entre moléculas antiapoptóticas (ex.: B-cell lymphoma protein 2 [BCL-2] e pró-apoptóticas (ex.: BCL-2 associated protein X [BAX]. OBJETIVO: O presente estudo objetivou avaliar a expressão de BCL-2 e BAX em tumores astrocíticos humanos. MATERIAL E MÉTODOS: Procedeu-se ao estudo imuno-histoquímico dessas proteínas utilizando-se o método da avidina-biotina-peroxidase em 55 astrocitomas (13 do grau I, 14 do II, sete do III e 21 do grau IV e cinco amostras de tecido cerebral não-tumoral (grupo controle. RESULTADOS: Os índices de positividade para BCL-2 e BAX demonstraram propensão ao acréscimo, de acordo com a gradação tumoral, com positividade geral de 43,26% e 24,67%, respectivamente. Essas proteínas não foram detectadas entre os espécimes não-tumorais. Os escores de marcação para BCL-2 apresentaram tendência ao aumento conforme a progressão histológica, enquanto os para BAX mostraram-se semelhantes nas diversas graduações. A análise conjunta dessas proteínas demonstrou significativa correlação com a gradação tumoral (p BACKGROUND: Astrocytomas represent the most frequent primary tumors of the central nervous system. Admittedly, part of tumor growth is due to inhibition of programmed cell death: the apoptosis. This phenomenon is basically regulated by the balance between anti-apoptotic (e.g.: B-cell lymphoma protein 2 [BCL-2] and pro-apoptotic (e.g.: BCL-2 associated protein X [BAX] molecules. OBJECTIVE: The present study aimed to evaluate the expression of BCL-2 and BAX in human astrocytic tumors of different histopathological grades. MATERIAL AND METHOD: An immunohistochemical study of those proteins using the avidin

  20. Temozolomide in malignant glioma

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    Gregor Dresemann

    2010-07-01

    Full Text Available Gregor DresemannCenter for Neurooncology at Aerztehaus Velen, Velen, GermanyAbstract: Glioblastoma multiforme WHO grade IV (GBM is the most aggressive ­malignant glioma and the most frequent primary tumor of the central nervous system. The median ­survival of newly diagnosed GBM patients was between 9 to 12 months prior to treatment with ­temozolomide being introduced. Primary resection that is as complete as possible is recommended for malignant glioma. Conventional fractionated irradiation 55 to 60 gy with concomitant temozolomide followed by standard temozolomide 6 cycles (5/28 (EORTC/NCIC-regime published by R Stupp in 2005 is the standard of care for newly diagnosed GBM after surgery, independent of the methylation status of the MGM-T gene promoter. Age is no ­contraindication for treatment with temozolomide, although comorbidity and performance status have to be ­considered. For temozolomide naive GBM and astrocytoma grade III patients with disease progression, temozolomide is still the treatment of choice outside of clinical studies. A ­general consensus regarding the schedule of choice has not yet been achieved; so far the 5 out of 28 days regimen (5/28 is the standard of care in most countries. Patients with disease progression after standard temozolomide (5/28 are candidates for clinical studies. Outside of clinical ­studies, dose-dense (7/7, prolonged (21/28, or metronomic (28/28 temozolomide, or alternatively a nitrosourea-based regimen can be an option. The excellent toxicity profile of ­temozolomide allows for various combinations with antitumor agents. None of these ­combinations, however, have been demonstrated to be statistically significantly superior compared to temozolomide alone. The role of lower dosed, dose-dense, or continuous regimen with or without drug combination and the role of temozolomide for newly diagnosed astrocytoma grade III and low grade glioma still has to be determined.Keywords: glioblastoma