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Sample records for adult pilocytic astrocytoma

  1. Dissemination patterns of pilocytic astrocytoma.

    PubMed

    Faria, Andréia V; Azevedo, Geovani C A; Zanardi, Verônica A; Ghizoni, Enrico; Queiroz, Luciano S

    2006-09-01

    Two patients with multifocal pilocytic astrocytoma diagnosed by magnetic resonance imaging (MRI) and confirmed by histopathological examination are reported. They presented distinct sites and mechanisms of metastasis: to distant ventricles through the cerebral spinal fluid (CSF) in patient 1 and to contralateral parenchyma, possibly through white matter tracts, in patient 2, a pathway not so far reported in pilocytic astrocytoma. Early detection of multifocal pilocytic astrocytoma by MRI may change treatment strategies and improve prognosis.

  2. A Pilocytic Astrocytoma Mimicking a Clinoidal Meningioma

    PubMed Central

    Hong, Christopher S.; Lehman, Norman L.; Sauvageau, Eric

    2014-01-01

    Pilocytic astrocytomas and meningiomas are benign, primary brain tumors that may involve the optic tract. Classically, the presence of a dural “tail” sign may differentiate a meningioma from other intracranial lesions. In this report, we describe a mass with the typical appearance of a clinoidal meningioma on magnetic resonance imaging (MRI) but postoperatively diagnosed as a pilocytic astrocytoma. This case illustrates the rare occurrence of a pilocytic astrocytoma mimicking a meningioma on MRI. PMID:24744944

  3. Histologically Benign, Clinically Aggressive: Progressive Non-Optic Pathway Pilocytic Astrocytomas in Adults with NF1

    PubMed Central

    Strowd, Roy E.; Rodriguez, Fausto J.; McLendon, Roger E.; Vredenburgh, James J.; Chance, Aaron B.; Jallo, George; Olivi, Alessandro; Ahn, Edward S.; Blakeley, Jaishri O.

    2016-01-01

    Although optic pathway gliomas are the most common brain tumors associated with neurofibromatosis type 1 (NF1), extra-optic gliomas occur and may behave more aggressively with outcomes that differ by age. A retrospective case-control study was designed to describe the clinical course of adult NF1 patients with progressive extra-optic pilocytic astrocytomas (PAs) and compare to a pediatric cohort. Data for patients treated at the Johns Hopkins Comprehensive Neurofibromatosis Center from 2003 to 2013 were reviewed to identify cases (adults, age >18) and controls (pediatric, age <18) with clinically or radiographically progressive extra-optic PAs. Demographic, clinical, histologic, and radiographic data were collected. Three adult NF1 cases and four pediatric NF1 controls were identified. Mean age was 32.3 ± 9.5 years, 66% male (cases); 12.8±4.2 years, 100% male (controls). Symptomatic progression occurred in two-of-three adults (67%) while the majority of pediatric patients presented with isolated radiographic progression (n=3, 75%). Onset tended to be more rapid in adults (4±1 vs. 14±8.3 months, P=0.10). Subtotal resection was the treatment for all pediatric patients. Radiotherapy (n=2), chemotherapy (n=2), and targeted, biologic agents (n=2) were administered in adults. Although all pediatric patients are living, outcomes were universally poor in adults with progression to death in all (median survival 17.1 months, range 6.6–30.3). In conclusion, despite grade I histology, all three adult NF1 patients with progressive extra-optic PAs suffered an aggressive clinical course which was not seen in pediatric patients. Clinicians should be aware of this clinico-histologic discrepancy when counseling and managing adult NF1 patients with progressive extra-optic PAs. PMID:26992069

  4. Histologically benign, clinically aggressive: Progressive non-optic pathway pilocytic astrocytomas in adults with NF1.

    PubMed

    Strowd, Roy E; Rodriguez, Fausto J; McLendon, Roger E; Vredenburgh, James J; Chance, Aaron B; Jallo, George; Olivi, Alessandro; Ahn, Edward S; Blakeley, Jaishri O

    2016-06-01

    Although optic pathway gliomas are the most common brain tumors associated with neurofibromatosis type 1 (NF1), extra-optic gliomas occur and may behave more aggressively with outcomes that differ by age. A retrospective case-control study was designed to describe the clinical course of adult NF1 patients with progressive extra-optic pilocytic astrocytomas (PAs) and compare to a pediatric cohort. Data for patients treated at the Johns Hopkins Comprehensive Neurofibromatosis Center from 2003 to 2013 were reviewed to identify cases (adults, age >18) and controls (pediatric, age <18) with clinically or radiographically progressive extra-optic PAs. Demographic, clinical, histologic, and radiographic data were collected. Three adult NF1 cases and four pediatric NF1 controls were identified. Mean age was 32.3 ± 9.5 years, 66% male (cases); 12.8 ± 4.2 years, 100% male (controls). Symptomatic progression occurred in two-of-three adults (67%) while the majority of pediatric patients presented with isolated radiographic progression (n = 3, 75%). Onset tended to be more rapid in adults (4 ± 1 vs. 14 ± 8.3 months, P = 0.10). Subtotal resection was the treatment for all pediatric patients. Radiotherapy (n = 2), chemotherapy (n = 2), and targeted, biologic agents (n = 2) were administered in adults. Although all pediatric patients are living, outcomes were universally poor in adults with progression to death in all (median survival 17.1 months, range 6.6-30.3). In conclusion, despite grade I histology, all three adult NF1 patients with progressive extra-optic PAs suffered an aggressive clinical course which was not seen in pediatric patients. Clinicians should be aware of this clinico-histologic discrepancy when counseling and managing adult NF1 patients with progressive extra-optic PAs. © 2016 Wiley Periodicals, Inc.

  5. Practical molecular pathologic diagnosis of pilocytic astrocytomas.

    PubMed

    Reis, Gerald F; Tihan, Tarik

    2015-03-01

    The pilocytic astrocytoma is predominantly a tumor of childhood and the most common type of circumscribed astrocytoma. The indolent nature of this tumor allows for prolonged survival for most patients, rendering the disease a rather "chronic" one, with potential long-term sequelae that are occasionally related to treatment. Two critical features of this tumor are its tendency to remain dormant, or involute even after subtotal resection, and the exceptional anaplastic transformation, sometimes following adjuvant therapy. The biological behavior of pilocytic astrocytoma can often be related to molecular alterations in the MAPK pathway.

  6. Pilocytic astrocytoma of the velum interpositum.

    PubMed

    Ideguchi, M; Nishizaki, T; Harada, K; Kwak, T; Murakami, T; Ito, H

    1998-05-01

    A 72-year-old male presented with a pilocytic astrocytoma in the velum interpositum manifesting as a 5-day history of dizziness attacks and unstable gait. Computed tomography and T1-weighted magnetic resonance imaging with gadolinium enhancement demonstrated a small, homogeneously enhanced mass in the velum interpositum. The tumor was removed subtotally, and the structure of the splenium was intact. The histological diagnosis was pilocytic astrocytoma. The MIB-1 growth fraction was 5%. The tumor may have originated from the splenium or the thalamus. The aggressive histology indicates the need for close neuroimaging follow-up.

  7. Coexistent dysembryoplastic neuroepithelial tumour and pilocytic astrocytoma

    PubMed Central

    Nasit, Jitendra G.; Shah, Payal; Zalawadia, Himanshu

    2016-01-01

    Dysembryoplastic neuroepithelial tumour (DNET) is an uncommon mixed glioneuronal tumour. DNET is classified as Grade I neoplasm in revised World Health Organization classification of tumors of the nervous system. DNET is commonly seen in the temporal lobe of children and young adults with features of pharmacoresistant complex partial seizures. Tumors arising in association with DNETs are rare. Only two cases of pilocytic astrocytoma (PA) arising in DNETs are reported. Surgical excision is the only successful management with favourable prognosis. The development of recurrence and malignancy after subtotal or even after complete excision challenges the premise of stability and highlights the importance of close clinical follow up. Here, a case of DNET with area of PA is described which helps in understanding the pathogenesis and biological behavior of DNET. PMID:27695565

  8. Suprasellar pilocytic astrocytoma in an adult with hemorrhage and leptomeningeal dissemination: case report and review of literature.

    PubMed

    Soliman, Radwa K; Budai, Caterina; Mundada, Pravin; Aljohani, Bakar; Rushing, Elisabeth J; Kollias, Spyros S

    2016-12-01

    Pilocytic astrocytoma (PA) is a low-grade tumor. It has an excellent prognosis after total resection. Leptomeningeal dissemination and hemorrhage are very rare to be associated with PA and lead to unfavorable prognosis. A 35-year-old man was diagnosed with a hemorrhagic suprasellar PA in 2006. Subsequent examination in 2007 revealed another large subdural hemorrhagic lesion in the sacral region, which proved to be PA by histopathologic assessment. Other leptomeningeal foci were discovered mainly at the craniocervical junction. The patient underwent subtotal resection and received chemotherapy with disease control for 7 years. Progression of the disseminated disease has recently occurred; however, the patient is still alive with stable disease after radiotherapy. The radiological features, management, and relevant literature are also presented. Our report heightens the awareness of PA in the adult population and the importance of close surveillance for the leptomeningeal spread, especially for sellar region tumors.

  9. Genetic alterations related to BRAF-FGFR genes and dysregulated MAPK/ERK/mTOR signaling in adult pilocytic astrocytoma.

    PubMed

    Pathak, Pankaj; Kumar, Anupam; Jha, Prerana; Purkait, Suvendu; Faruq, Mohammed; Suri, Ashish; Suri, Vaishali; Sharma, Mehar C; Sarkar, Chitra

    2016-09-08

    Pilocytic astrocytomas occur rarely in adults and show aggressive tumor behavior. However, their underlying molecular-genetic events are largely uncharacterized. Hence, 59 adult pilocytic astrocytoma (APA) cases of classical histology were studied (MIB-1 LI: 1%-5%). Analysis of BRAF alterations using qRT-PCR, confirmed KIAA1549-BRAF fusion in 11 (19%) and BRAF-gain in 2 (3.4%) cases. BRAF-V600E mutation was noted in 1 (1.7%) case by sequencing. FGFR1-mutation and FGFR-TKD duplication were seen in 7/59 (11.9%) and 3/59 (5%) cases, respectively. Overall 36% of APAs harbored BRAF and/or FGFR genetic alterations. Notably, FGFR related genetic alterations were enriched in tumors of supratentorial region (8/25, 32%) as compared with other locations (P = 0.01). The difference in age of cases with FGFR1-mutation (Mean age ± SD: 37.2 ± 15 years) vs. KIAA1549-BRAF fusion (Mean age ± SD: 25.1 ± 4.1 years) was statistically significant (P = 0.03). Combined BRAF and FGFR alterations were identified in 3 (5%) cases. Notably, the cases with more than one genetic alteration were in higher age group (Mean age ± SD: 50 ± 12 years) as compared with cases with single genetic alteration (Mean age ± SD: 29 ± 10; P = 0.003). Immunopositivity of p-MAPK/p-MEK1 was found in all the cases examined. The pS6-immunoreactivity, a marker of mTOR activation was observed in 34/39 (87%) cases. Interestingly, cases with BRAF and/or FGFR related alteration showed significantly lower pS6-immunostatining (3/12; 25%) as compared with those with wild-type BRAF and/or FGFR (16/27; 59%) (P = 0.04). Further, analysis of seven IDH wild-type adult diffuse astrocytomas (DA) showed FGFR related genetic alterations in 43% cases. These and previous results suggest that APAs are genetically similar to IDH wild-type adult DAs. APAs harbor infrequent BRAF alterations but more frequent FGFR alterations as compared with pediatric cases. KIAA1549-BRAF fusion

  10. Radiation Therapy for Pilocytic Astrocytomas of Childhood

    SciTech Connect

    Mansur, David B.; Rubin, Joshua B.; Kidd, Elizabeth A.; King, Allison A.; Hollander, Abby S.; Smyth, Matthew D.; Limbrick, David D.; Park, T.S.; Leonard, Jeffrey R.

    2011-03-01

    Purpose: Though radiation therapy is generally considered the most effective treatment for unresectable pilocytic astrocytomas in children, there are few data to support this claim. To examine the efficacy of radiation therapy for pediatric pilocytic astrocytomas, we retrospectively reviewed the experience at our institution. Methods and Materials: Thirty-five patients 18 years old or younger with unresectable tumors and without evidence of neurofibromatosis have been treated since 1982. Patients were treated with local radiation fields to a median dose of 54 Gy. Six patients were treated with radiosurgery to a median dose of 15.5 Gy. Five patients were treated with initial chemotherapy and irradiated after progression. Results: All patients were alive after a median follow-up of 5.0 years. However, progression-free survival was 68.7%. None of 11 infratentorial tumors progressed compared with 6 of 20 supratentorial tumors. A trend toward improved progression-free survival was seen with radiosurgery (80%) compared with external beam alone (66%), but this difference did not reach statistical significance. Eight of the 9 patients progressing after therapy did so within the irradiated volume. Conclusions: Although the survival of these children is excellent, almost one third of patients have progressive disease after definitive radiotherapy. Improvements in tumor control are needed in this patient population, and the optimal therapy has not been fully defined. Prospective trials comparing initial chemotherapy to radiation therapy are warranted.

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

    PubMed

    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.

  12. Outcome of Patients With Pilocytic Astrocytoma and Leptomeningeal Dissemination

    SciTech Connect

    Mazloom, Ali; Hodges, Joseph C.; Teh, Bin S.; Chintagumpala, Murali; Paulino, Arnold C.

    2012-10-01

    Purpose: To determine the patient, tumor, and treatment characteristics of patients with pilocytic astrocytoma (PA) and leptomeningeal dissemination (LMD). Methods and Materials: A PubMed search of English-language studies pertaining to PA with LMD was performed using a combination of keywords that included juvenile pilocytic astrocytoma, low-grade astrocytoma, low-grade glioma, leptomeningeal dissemination, neuraxis spread, and radiotherapy. We found 26 studies with 58 patients between 1976 and 2005 that met these criteria. Results: The median survival for PA patients with LMD was 65 months. The 1-, 2-, and 5-year overall survival (OS) rate after the diagnosis of LMD was 81.1%, 75.7%, and 55.5%. The 1-, 2-, and 5-year progression-free survival (PFS) rate after the diagnosis of LMD was 69.3%, 66.5%, and 34.6%, respectively. Age, gender, primary site location, timing of LMD presentation (synchronous vs. metachronous), and LMD location did not significantly influence OS or PFS. No statistically significant difference was found in OS or PFS between the chemotherapy and radiotherapy groups. Likewise, no difference was found in OS or PFS according to the use of craniospinal irradiation vs. less extensive RT fields. Conclusions: Approximately one-half of PA patients were alive 5 years after the diagnosis of LMD. Both chemotherapy and radiotherapy have efficacy against LMD. Although the use of craniospinal irradiation did not have an effect on PFS, the patient numbers were small and a larger number treated with craniospinal irradiation is needed to determine its efficacy.

  13. IDH1 R132H mutation in a pilocytic astrocytoma: a case report

    PubMed Central

    Behling, Felix; Steinhilber, Julia; Tatagiba, Marcos; Bisdas, Sotirios; Schittenhelm, Jens

    2015-01-01

    We present the case of a 72-year old female with a right cerebellar pilocytic astrocytoma WHO grade I with an Isocitrate dehydrogenase 1 (IDH1) R132H mutation. The patient is recurrence-free 6 years after the initial diagnosis. Only one single case with strikingly similar clinicopathological features has been reported before. Otherwise, IDH1/2 mutations are not seen in pilocytic astrocytomas. The clinical implications of these findings are discussed. PMID:26617931

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

    PubMed Central

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

    2015-01-01

    Context: 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. Case Description: 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. Conclusions: 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. PMID:26252356

  15. Non-random aneuploidy specifies subgroups of pilocytic astrocytoma and correlates with older age

    PubMed Central

    Khuong-Quang, Dong-Anh; Bechet, Denise; Gayden, Tenzin; Kool, Marcel; De Jay, Nicolas; Jacob, Karine; Gerges, Noha; Hutter, Barbara; Şeker-Cin, Huriye; Witt, Hendrik; Montpetit, Alexandre; Brunet, Sébastien; Lepage, Pierre; Bourret, Geneviève; Klekner, Almos; Bognár, László; Hauser, Peter; Garami, Miklós; Farmer, Jean-Pierre; Montes, Jose-Luis; Atkinson, Jeffrey; Lambert, Sally; Kwan, Tony; Korshunov, Andrey; Tabori, Uri; Collins, V. Peter; Albrecht, Steffen; Faury, Damien; Pfister, Stefan M.; Paulus, Werner; Hasselblatt, Martin; Jones, David T.W.; Jabado, Nada

    2015-01-01

    Pilocytic astrocytoma (PA) is the most common brain tumor in children but is rare in adults, and hence poorly studied in this age group. We investigated 222 PA and report increased aneuploidy in older patients. Aneuploid genomes were identified in 45% of adult compared with 17% of pediatric PA. Gains were non-random, favoring chromosomes 5, 7, 6 and 11 in order of frequency, and preferentially affecting non-cerebellar PA and tumors with BRAF V600E mutations and not with KIAA1549-BRAF fusions or FGFR1 mutations. Aneuploid PA differentially expressed genes involved in CNS development, the unfolded protein response, and regulators of genomic stability and the cell cycle (MDM2, PLK2),whose correlated programs were overexpressed specifically in aneuploid PA compared to other glial tumors. Thus, convergence of pathways affecting the cell cycle and genomic stability may favor aneuploidy in PA, possibly representing an additional molecular driver in older patients with this brain tumor. PMID:26378811

  16. Stereotactic Radiosurgery for Recurrent or Unresectable Pilocytic Astrocytoma

    SciTech Connect

    Hallemeier, Christopher L.; Pollock, Bruce E.; Schomberg, Paula J.; Link, Michael J.; Brown, Paul D.; Stafford, Scott L.

    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.

  17. Diffuse Spinal Leptomeningeal Spread of a Pilocytic Astrocytoma in a 3-year-old Child.

    PubMed

    Alyeldien, Ameer; Teuber-Hanselmann, Sarah; Cheko, Azad; Höll, Tanja; Scholz, Martin; Petridis, Athanasios K

    2016-03-25

    Pilocytic astrocytomas correspond to low-grade gliomas and therefore metastasize exceedingly rare. However, pilocytic astrocytomas are able to and leptomeningeal dissemination may be seen. What are the treatment options of these cases? We present a case report of a 3-year-old child with a pilocytic astrocytoma of the optic chiasm with leptomeningeal dissemination of the spinal meninges. Partial resection of the cerebral tumor has been performed. Since the leptomeningeal dissemination was seen all over the spinal meninges, the child did not undergo further surgical treatment. A wait and watch strategy were followed. Chemotherapy was initiated, if a 25% tumor growth was seen. Leptomeningeal dissemination of a pilocytic astrocytoma is seen so infrequently that no standard therapy is established. Since these metastases may occur even up to 2 decades after primary tumor resection, long-term follow-up is indicated. In case of spinal metastases, surgical treatment should be performed if feasible. Otherwise observation should be possessed and/or chemotherapy should be initiated.

  18. Diffuse Spinal Leptomeningeal Spread of a Pilocytic Astrocytoma in a 3-year-old Child

    PubMed Central

    Alyeldien, Ameer; Teuber-Hanselmann, Sarah; Cheko, Azad; Höll, Tanja; Scholz, Martin; Petridis, Athanasios K.

    2016-01-01

    Pilocytic astrocytomas correspond to low-grade gliomas and therefore metastasize exceedingly rare. However, pilocytic astrocytomas are able to and leptomeningeal dissemination may be seen. What are the treatment options of these cases? We present a case report of a 3-year-old child with a pilocytic astrocytoma of the optic chiasm with leptomeningeal dissemination of the spinal meninges. Partial resection of the cerebral tumor has been performed. Since the leptomeningeal dissemination was seen all over the spinal meninges, the child did not undergo further surgical treatment. A wait and watch strategy were followed. Chemotherapy was initiated, if a 25% tumor growth was seen. Leptomeningeal dissemination of a pilocytic astrocytoma is seen so infrequently that no standard therapy is established. Since these metastases may occur even up to 2 decades after primary tumor resection, long-term follow-up is indicated. In case of spinal metastases, surgical treatment should be performed if feasible. Otherwise observation should be possessed and/or chemotherapy should be initiated. PMID:27162602

  19. Tandem duplication producing a novel oncogenic BRAF fusion gene defines the majority of pilocytic astrocytomas

    PubMed Central

    Jones, David T. W.; Kocialkowski, Sylvia; Liu, Lu; Pearson, Danita M.; Bäcklund, L. Magnus; Ichimura, Koichi; Collins, V. Peter

    2008-01-01

    Brain tumours are the commonest solid tumours of childhood, and pilocytic astrocytomas (PAs) are the most common central nervous system tumour in 5-19 year-olds. Little is known about the genetic alterations underlying their development. Here we describe a tandem duplication of ∼2Mb at 7q34 occurring in 66% of pilocytic astrocytomas. This rearrangement, which was not observed in a series of 244 higher-grade astrocytomas, results in an in-frame fusion gene incorporating the kinase domain of the BRAF oncogene. We further show that the resulting fusion protein has constitutive BRAF kinase activity, and is able to transform NIH3T3 cells. This is the first report of BRAF activation through rearrangement as a frequent feature in a sporadic tumor. The frequency and specificity of this change underline its potential both as a therapeutic target and a diagnostic tool. PMID:18974108

  20. Leptomeningeal dissemination of pilocytic astrocytoma in a 17-year-old boy.

    PubMed

    Jandaghi, Ali BabaeI; Bidabadi, Elham; Saadat, Seyed; Alijani, Babak; Daliri, Saeid; Reyhanian, Zoheir; Mashouf, Mehryar

    2014-01-01

    Pilocytic astrocytoma with leptomeningeal dissemination is a rare phenomenon and can be associated with obstructive hydrocephalus and an unfavorable prognosis. Herein, we report a seventeen-year-old boy with a history of ventriculo-peritoneal shunt insertion due to severe hydrocephalus who presented with progressive headache and vomiting together with ocular and cerebellar signs and symptoms. Neuroimaging confirmed the presence of multiple intracranial masses in the cerebellum and thalamus. Intracranial dissemination of tumor to the the leptomeninges was seen during neuroendoscopy. Simultaneous biopsy and endoscopic third ventriculostomy were performed and the diagnosis of low-grade pilocytic astrocytoma with leptomeningeal dissemination was made by histological examination. The patient underwent chemotherapy in combination with radiotherapy to reduce the risk of reoccurrence of the primary tumor and was followed for one year.

  1. TP53 codon 72 polymorphism may predict early tumour progression in paediatric pilocytic astrocytoma

    PubMed Central

    Mascelli, Samantha; Nozza, Paolo; Jones, David T.W.; Colin, Carole; Pistorio, Angela; Milanaccio, Claudia; Ravegnani, Marcello; Consales, Alessandro; Witt, Olaf; Morana, Giovanni; Cama, Armando; Capra, Valeria; Biassoni, Roberto; Pfister, Stefan M.; Figarella-Branger, Dominique; Garrè, Maria Luisa; Raso, Alessandro

    2016-01-01

    Pilocytic astrocytoma and ganglioglioma may occur in inaccessible or surgically difficult areas. In case of incomplete resection, the availability of biological predictors of tumour progression could be particularly important. To this end, an analysis of p53 codon 72 polymorphism and assessment of its role as prognostic marker were performed. The status of the p53 Arg72Pro polymorphism was evaluated by pyrosequencing method in a multicenter cohort of 170 paediatric patients. Genotype/phenotype associations were investigated either by means of bivariate or multivariate analyses. In the partially resected pilocytic astrocytomas, the Arg/Arg variant predicts early tumour progression (median survival time: 23.1 months) and is associated with poor event-free survival (p value = 0.0009). This finding remains true also in case of adjuvant therapies, with a 5-year event-free survival of 30.6% for cases with Arg/Arg variant vs. 78.7% for those with other genotypes. There is no association between ganglioglioma and the polymorphism. The assessment of Arg/Arg variant could improve the management of pilocytic astrocytoma. TP53 codon 72 analysis could distinguish low-risk cases, in which surgery could be conservative, from high-risk cases needing an aggressive surgery plan. PMID:27374106

  2. Preliminary observations on genetic alterations in pilocytic astrocytomas associated with neurofibromatosis 1.

    PubMed Central

    Tada, Kenji; Kochi, Masato; Saya, Hideyuki; Kuratsu, Jun-ichi; Shiraishi, Shoji; Kamiryo, Takanori; Shinojima, Naoki; Ushio, Yukitaka

    2003-01-01

    Neurofibromatosis 1 (NF1) is an autosomal dominant disorder that predisposes sufferers to various forms of neoplasia. Among affected individuals, 15%-20% develop astrocytomas, especially pilocytic astrocytomas (PA), which are benign and classified as grade I by the World Health Organization. They are generally well circumscribed, and their progression is slow. NF1-associated PAs (NF1-PAs) occasionally behave as aggressive tumors. To elucidate underlying genetic events in clinically progressive NF1-PAs, we performed molecular genetic analysis on 12 PAs, including 3 NF1-PAs, for pS3, p16, and epidermal growth factor receptor genes, as well as loss of heterozygosity (LOH) on chromosome 1p, 10, 17, and 19q. None of the obvious genetic alterations typically seen in higher grade astrocytomas were found in 9 sporadic PAs. However, in 2 of 3 NF1-PAs, microsatellite analysis showed LOH10, including the PTEN (phosphatase and tensin homolog deleted on chromosome 10) gene locus, despite the diagnosis of pilocytic astrocytoma;one of these also manifested homozygous deletion of the p16 gene. The other NF1-PA harbored only LOH of the NF1 gene locus (17q). Our preliminary results support the hypothesis that some NF1-PAs differ genetically from sporadic PAs. PMID:14565158

  3. [Leptomeningeal spread of an intramedullary cervical pilocytic astrocytoma: case report and literature review].

    PubMed

    Jusué-Torres, I; Alcázar-Vaquerizo, L; Gómez-Angulo, J C; Navarro-Torres, R; López-Serrano, R; García-Miralles, N

    2011-10-01

    BACKGROUND. The rarest location of pilocytic astrocytoma is intramedullary. Gliomas represent up to 24 - 30% of intramedullary tumors in adulthood and are second only after ependymomas. Leptomeningeal dissemination through cerebrospinal fluid is unusual and occurs predominantly in medulloblastomas, ependymoblastomas, central neuroblastomas, ependymomas, germ cell tumors and high-grade gliomas. The majority of spinal cord gliomas reporting metastasis were anaplastic astrocytomas or glioblastomas multiforme and relatively few were low-grade gliomas. The incidence of leptomeningeal spread of low-grade tumors is rare. A rare cranial extension of brain leptomeningeal dissemination in an intramedullary pilocytic astrocytoma during adulthood is reported. CASE REPORT. A 51 year-old-man with a recurrent intramedullary mass at C5-C7 level operated 4 times with all pathological anatomy reports describing the lesion as Pilocytic Astrocytoma developed, after 15 years from the diagnosis, visual hallucinations and his level of consciousness worsened to Glasgow coma score 13/15. The MRI showed highly enhanced cranial and spinal leptomeninges and paquimeninges with a micro nodular-granulomatous aspect associated with intense affectation of basal cisterns, subarachnoid spaces and convexity of both cerebral hemispheres suggestive of leptomeningeal spread of the spinal mass. The patient expired after three days. CONCLUSION. Leptomeningeal spread is a rare phenomenon and when it happens usually doesn't change the primary tumor's behavior. In our case the aggressiveness could be explained by a potential malignization of the primary tumor that it was not documented because of the partial resections from the lasts surgeries or instead the tumor was actually a monomorphous pilomyxoid tumor.

  4. Somatic neurofibromatosis type 1 (NF1) inactivation characterizes NF1-associated pilocytic astrocytoma.

    PubMed

    Gutmann, David H; McLellan, Michael D; Hussain, Ibrahim; Wallis, John W; Fulton, Lucinda L; Fulton, Robert S; Magrini, Vincent; Demeter, Ryan; Wylie, Todd; Kandoth, Cyriac; Leonard, Jeffrey R; Guha, Abhijit; Miller, Christopher A; Ding, Li; Mardis, Elaine R

    2013-03-01

    Low-grade brain tumors (pilocytic astrocytomas) arising in the neurofibromatosis type 1 (NF1) inherited cancer predisposition syndrome are hypothesized to result from a combination of germline and acquired somatic NF1 tumor suppressor gene mutations. However, genetically engineered mice (GEM) in which mono-allelic germline Nf1 gene loss is coupled with bi-allelic somatic (glial progenitor cell) Nf1 gene inactivation develop brain tumors that do not fully recapitulate the neuropathological features of the human condition. These observations raise the intriguing possibility that, while loss of neurofibromin function is necessary for NF1-associated low-grade astrocytoma development, additional genetic changes may be required for full penetrance of the human brain tumor phenotype. To identify these potential cooperating genetic mutations, we performed whole-genome sequencing (WGS) analysis of three NF1-associated pilocytic astrocytoma (PA) tumors. We found that the mechanism of somatic NF1 loss was different in each tumor (frameshift mutation, loss of heterozygosity, and methylation). In addition, tumor purity analysis revealed that these tumors had a high proportion of stromal cells, such that only 50%-60% of cells in the tumor mass exhibited somatic NF1 loss. Importantly, we identified no additional recurrent pathogenic somatic mutations, supporting a model in which neuroglial progenitor cell NF1 loss is likely sufficient for PA formation in cooperation with a proper stromal environment.

  5. Leksell Gamma Knife treatment for pilocytic astrocytomas: long-term results.

    PubMed

    Simonova, Gabriela; Kozubikova, Petra; Liscak, Roman; Novotny, Josef

    2016-07-01

    OBJECTIVE The purpose of this study was to evaluate long-term treatment results, radiation-related toxicity, and prognostic factors for the progression-free survival (PFS) of patients with pilocytic astrocytomas treated by means of stereotactic radiosurgery with a Leksell Gamma Knife. METHODS A total of 25 patients with pilocytic astrocytomas underwent Gamma Knife surgery during the period 1992-2002. The median target volume was 2700 mm(3) (range 205-25,000 mm(3)). The 18 patients treated with 5 daily fractions received a median minimum target dose of 25 Gy. Doses for the 2 patients treated with 10 fractions over 5 days (2 fractions delivered on the same day at least 6 hours apart) were 23 and 28 Gy. For the 5 patients treated with a single fraction, the minimum target dose ranged from 13 to 20 Gy (median 16 Gy). RESULTS Complete regression occurred in 10 patients (40%) and partial regression in 10 patients (40%). The 10-year overall survival rate was 96% and the 10-year PFS rate was 80%. Target volume appeared to be a significant prognostic factor for PFS (p = 0.037). Temporary Grade 3 toxicity appeared in 2 patients (8%), and these patients were treated with corticosteroids for 2 months. Permanent Grade 4 toxicity appeared in 2 patients (8%) and was associated with neurocognitive dysfunction. In these 2 individuals, the neurocognitive dysfunction was also felt to be in part the result of the additional therapeutic interventions (4 in one case and 6 in the other) required to achieve durable control of their tumors. CONCLUSIONS Radiosurgery represents an alternative treatment modality for small residual or recurrent volumes of pilocytic astrocytomas and provides long-term local control. Target volume appears to be the most important factor affecting PFS.

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

    ERIC Educational Resources Information Center

    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…

  7. Cerebellar Mutism Syndrome After Posterior Fossa Surgery: A Report of Two Cases of Pilocytic Astrocytoma

    PubMed Central

    GÜNDÜZ, Hasan Burak; YASSA, Mustafa İlker Kuntay; OFLUOĞLU, Ali Ender; POSTALCI, Lütfü; EMEL, Erhan

    2013-01-01

    Cerebellar mutism is a type of syndrome including decreased speech, hypotonia, ataxia and emotional instability which occurs after posterior fossa surgery. It has been first reported by Rekate et al. and Yonemasu in 1985. It is well known that long tract signs and lower cranial nerve involvement are not seen with this syndrome and understanding is preserved. However, the pathophysiology of cerebellar mutism has not been well clarified yet. It is mainly seen in patients with medulloblastoma and brainstem involvement. In this report, we present two extraordinary cases of cerebellar mutism after posterior fossa surgery. They were considered extraordinary because their hystopathological analysis results yielded pilocytic astrocytoma which is out of the predefined risk factors.

  8. A Case of Central Precocious Puberty Due to Concomitant Hypothalamic Hamartoma and Juvenile Pilocytic Astrocytoma

    PubMed Central

    Çatlı, Gönül; Abacı, Ayhan; Anık, Ahmet; Güleryüz, Handan; Özer, Erdener; Öcal, İrfan; Yüceer, Nurullah; Mutafoğlu, Kamer

    2014-01-01

    Central precocious puberty (CPP) is caused by premature activation of the hypothalamo-pituitary-gonadal axis. More than 50% of boys with CPP have an identifiable etiology. Hypothalamic hamartoma (HH), hydrocephalus, tumors, infections, congenital defects, ischemia, radiation, or injury of the brain are the most common causes of secondary CPP. In this report, we present the case of a 2 years and 9 months old male patient who had a 30x40 mm contrast-enhancing suprasellar mass and was histopathologically diagnosed with giant HH. However, since HHs are designated as non-enhancing masses, considering the possibility of an incomplete diagnosis of a glial tumor, the patient was followed up. Clinical and radiological follow-up revealed stable findings with no evidence of tumor growth until the third year after surgery when he presented with neurological deficit due to the rapid growth of the suprasellar mass. After the second surgery, histopathological examination of the biopsy specimen revealed the lesion to be a juvenile pilocytic astrocytoma (PA). The concomitance of HH and juvenile PA is very rare. To our knowledge, this is the first report of a patient with concomitant juvenile PA and HH who developed CPP and did not have gelastic epilepsy despite the rapidly growing giant mass. PMID:25241615

  9. OP32A COMBINED STRATEGY FOR THE DETECTION OF BRAF FUSIONS IN PILOCYTIC ASTROCYTOMA USING RT-PCR AND FISH

    PubMed Central

    Faulkner, C.; Shaw, A.; Wragg, C.; Greenslade, M.; Haynes, H.; Williams, H.; Lowis, S.; Williams, M.; Kurian, K.M.

    2014-01-01

    INTRODUCTION: Pilocytic astrocytomas can show a wide morphological spectrum making definitive histological diagnosis challenging. The FISH test for KIAA1549-BRAF fusions is most commonly used, but this is difficult to interpret. We aimed to develop a real-time PCR (RT-PCR) test as a first-line screen for the three most common KIAA1549-BRAF fusion variants. METHOD: A RT-PCR method for detecting KIAA1549-BRAF fusions from formalin-fixed paraffin-embedded (FFPE) brain tumour tissues (pilocytic astrocytoma). The three most common fusion variants are detected using this assay: exon 16 of KIAA1549 fused to exon 9 of BRAF, exon 15 of KIAA1549 fused to exon 9 of BRAF and exon 16 of KIAA1549 fused to exon 11 of BRAF fusion. GAPDH expression was used as a control. RESULTS: The RT-PCR assay was initially validated on 12 samples previously tested by FISH or RT-PCR in a different laboratory. The RT-PCR assay had a sensitivity of 89% (8/9 - one sample tested positive by FISH but negative on RT-PCR) and a specificity of 100% (2/2). The failure rate was 8.3% (1/12). Sensitivity experiments showed that the fusion can be detected when present at a least 5% of the total cDNA content. 51 Neuropathology diagnostic FFPE samples from 42 pilocytic astrocytoma patients were then tested using the BRAF fusion RT-PCR assay. The overall pick-up rate was 54% (20/37 patients) Of the positive patients (20), 55% (11/20) had the 16-9 fusion and 45% (9/20) had the 15-9 fusion. Two patients had multiple fusions (2/20 positive patients, 10%) showing the 16-9 fusion and a low-level 16-11 fusion. No patients exclusively had the 16-11 fusion. CONCLUSION: We propose RTPCR first line for fusion analysis followed by FISH, for pilocytic astrocytoma.

  10. Long survival in a child with a mutated K27M-H3.3 pilocytic astrocytoma

    PubMed Central

    Hochart, Audrey; Escande, Fabienne; Rocourt, Nathalie; Grill, Jacques; Koubi-Pick, Valérie; Beaujot, Juliette; Meignan, Samuel; Vinchon, Matthieu; Maurage, Claude Alain; Leblond, Pierre

    2015-01-01

    We report the first case of a child with a H3F3A K27M mutated pilocytic astrocytoma, who presented with a 10 years survival, and underwent spontaneous malignant transformation. The complex tumoral chromosomal rearrangements were consistent for genomic instability and for the histopathological features of malignant transformation into glioblastoma. H3F3A K27M mutations are rarely observed in benign neoplasms and may be associated with an adverse outcome. This mutation might not be the major driver that led to the onset of tumorigenesis, and we could consider that the associated TP53 mutation, would be required for malignant transformation. PMID:25909089

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

    PubMed

    Buder, Thomas; Deutsch, Andreas; Klink, Barbara; Voss-Böhme, Anja

    2015-12-01

    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.

  12. 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

    SciTech Connect

    Hou, P; Park, P; Li, H; Zhu, X; Mahajan, A; Grosshans, D

    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.

  13. Pilocytic Midbrain Astrocytoma Presenting with Fresh Bleed after Twenty-one-years Survival Following First Surgery: A Unique Case of Longest Brainstem Glioma Survival

    PubMed Central

    Satyarthee, Guru Dutta; Sudhan, M. D.; Mehta, V. S.

    2016-01-01

    Brainstem glioma usually carries a poor prognosis and prolonged survival is very infrequent. In a detailed Pubmed, Medline search for prolonged survival, authors could got a longest survival only up to seventeen years, reported by Umehara et al, who was subjected to gamma knife therapy and got symptomatic, MRI brain reveled large tumor growth during pregnancy necessitating emergency surgery and histopathological diagnosis was pilocytic astrocytoma. Authors report an interesting case of midbrain glioma diagnosed 21 years back, who underwent gross resection in the year 1993, histopathology was pilocytic astrocytoma, WHO grade I, and received gamma knife surgery for residual subsequently and he presented with sudden onset left sided hemiplegia on the current admission. The cranial MRI imaging revealed an infarct involving right hemi midbrain, contrast MRI brain revealed no residual glioma. To the best knowledge of authors such prolonged survival is not reported with a case of brainstem glioma survived twenty- one years with non residual tumor on the last imaging study represents first case of its kind in the western literature and probably developed hemiplegia due to bleed, highlighting bleed as delayed complication following gamma knife therapy for cranial tumors PMID:28163514

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

    PubMed

    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

    2016-12-17

    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

  15. BRAF Fusion Analysis in Pilocytic Astrocytomas: KIAA1549-BRAF 15-9 Fusions Are More Frequent in the Midline Than Within the Cerebellum

    PubMed Central

    Faulkner, Claire; Ellis, Hayley Patricia; Shaw, Abigail; Penman, Catherine; Palmer, Abigail; Wragg, Christopher; Greenslade, Mark; Haynes, Harry Russell; Williams, Hannah; Lowis, Stephen; White, Paul; Williams, Maggie; Capper, David; Kurian, Kathreena Mary

    2015-01-01

    Abstract Pilocytic astrocytomas (PAs) are increasingly tested for KIAA1549-BRAF fusions. We used reverse transcription polymerase chain reaction for the 3 most common KIAA1549-BRAF fusions, together with BRAF V600E and histone H3.3 K27M analyses to identify relationships of these molecular characteristics with clinical features in a cohort of 32 PA patients. In this group, the overall BRAF fusion detection rate was 24 (75%). Ten (42%) of the 24 had the 16-9 fusion, 8 (33%) had only the 15-9 fusion, and 1 (4%) of the patients had only the 16-11 fusion. In the PAs with only the 15-9 fusion, 1 PA was in the cerebellum and 7 were centered in the midline outside of the cerebellum, that is, in the hypothalamus (n = 4), optic pathways (n = 2), and brainstem (n = 1). Tumors within the cerebellum were negatively associated with fusion 15-9. Seven (22%) of the 32 patients had tumor-related deaths and 25 of the patients (78%) were alive between 2 and 14 years after initial biopsy. Age, sex, tumor location, 16-9 fusion, and 15-9 fusion were not associated with overall survival. Thus, in this small cohort, 15-9 KIAA1549-BRAF fusion was associated with midline PAs located outside of the cerebellum; these tumors, which are generally difficult to resect, are prone to recurrence. PMID:26222501

  16. BRAF Fusion Analysis in Pilocytic Astrocytomas: KIAA1549-BRAF 15-9 Fusions Are More Frequent in the Midline Than Within the Cerebellum.

    PubMed

    Faulkner, Claire; Ellis, Hayley Patricia; Shaw, Abigail; Penman, Catherine; Palmer, Abigail; Wragg, Christopher; Greenslade, Mark; Haynes, Harry Russell; Williams, Hannah; Lowis, Stephen; White, Paul; Williams, Maggie; Capper, David; Kurian, Kathreena Mary

    2015-09-01

    Pilocytic astrocytomas (PAs) are increasingly tested for KIAA1549-BRAF fusions. We used reverse transcription polymerase chain reaction for the 3 most common KIAA1549-BRAF fusions, together with BRAF V600E and histone H3.3 K27M analyses to identify relationships of these molecular characteristics with clinical features in a cohort of 32 PA patients. In this group, the overall BRAF fusion detection rate was 24 (75%). Ten (42%) of the 24 had the 16-9 fusion, 8 (33%) had only the 15-9 fusion, and 1 (4%) of the patients had only the 16-11 fusion. In the PAs with only the 15-9 fusion, 1 PA was in the cerebellum and 7 were centered in the midline outside of the cerebellum, that is, in the hypothalamus (n = 4), optic pathways (n = 2), and brainstem (n = 1). Tumors within the cerebellum were negatively associated with fusion 15-9. Seven (22%) of the 32 patients had tumor-related deaths and 25 of the patients (78%) were alive between 2 and 14 years after initial biopsy. Age, sex, tumor location, 16-9 fusion, and 15-9 fusion were not associated with overall survival. Thus, in this small cohort, 15-9 KIAA1549-BRAF fusion was associated with midline PAs located outside of the cerebellum; these tumors, which are generally difficult to resect, are prone to recurrence.

  17. Astrocytoma

    MedlinePlus

    ... Astrocytoma— These grade II astrocytomas tend to invade surrounding tissue and grow at a relatively slow pace. ... to have tentacle-like projections that grow into surrounding tissue, making them difficult to completely remove during ...

  18. Activation of mTORC1/mTORC2 signaling in pediatric low-grade glioma and pilocytic astrocytoma reveals mTOR as a therapeutic target

    PubMed Central

    Hütt-Cabezas, Marianne; Karajannis, Matthias A.; Zagzag, David; Shah, Smit; Horkayne-Szakaly, Iren; Rushing, Elisabeth J.; Cameron, J. Douglas; Jain, Deepali; Eberhart, Charles G.; Raabe, Eric H.; Rodriguez, Fausto J.

    2013-01-01

    Background Previous studies support a role for mitogen-activated protein kinase pathway signaling, and more recently Akt/mammalian target of rapamycin (mTOR), in pediatric low-grade glioma (PLGG), including pilocytic astrocytoma (PA). Here we further evaluate the role of the mTORC1/mTORC2 pathway in order to better direct pharmacologic blockade in these common childhood tumors. Methods We studied 177 PLGGs and PAs using immunohistochemistry and tested the effect of mTOR blockade on 2 PLGG cell lines (Res186 and Res259) in vitro. Results Moderate (2+) to strong (3+) immunostaining was observed for pS6 in 107/177 (59%) PAs and other PLGGs, while p4EBP1 was observed in 35/115 (30%), pElF4G in 66/112 (59%), mTOR (total) in 53/113 (47%), RAPTOR (mTORC1 component) in 64/102 (63%), RICTOR (mTORC2 component) in 48/101 (48%), and pAkt (S473) in 63/103 (61%). Complete phosphatase and tensin homolog protein loss was identified in only 7/101 (7%) of cases. In PA of the optic pathways, compared with other anatomic sites, there was increased immunoreactivity for pS6, pElF4G, mTOR (total), RICTOR, and pAkt (P < .05). We also observed increased pS6 (P = .01), p4EBP1 (P = .029), and RICTOR (P = .05) in neurofibromatosis type 1 compared with sporadic tumors. Treatment of the PLGG cell lines Res186 (PA derived) and Res259 (diffuse astrocytoma derived) with the rapalog MK8669 (ridaforolimus) led to decreased mTOR pathway activation and growth. Conclusions These findings suggest that the mTOR pathway is active in PLGG but varies by clinicopathologic subtype. Additionally, our data suggest that mTORC2 is differentially active in optic pathway and neurofibromatosis type 1–associated gliomas. MTOR represents a potential therapeutic target in PLGG that merits further investigation. PMID:24203892

  19. Efficacy of 68Ga-DOTATOC Positron Emission Tomography (PET) CT in Children and Young Adults With Brain Tumors

    ClinicalTrials.gov

    2016-09-07

    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

  20. Pilomyxoid astrocytoma of the cerebellum.

    PubMed

    Ajani, Olufemi A; Al Sulaiti, Ghanem; Al Bozom, Issam

    2011-05-01

    Pilomyxoid astrocytomas (PMAs) are low-grade (WHO Grade II) tumors for which the imaging features are similar to pilocytic astrocytomas (PAs), but for which histological features and the clinical course differ. They are classified as a variant of PA. They have only been recently recognized, and they behave more aggressively than PAs. Most cases occur in the hypothalamic-chiasmatic area, although they may be located in any part of the neuraxis. Posterior fossa PMAs are very rare. The authors report a case of a 2-year-old girl with cerebellar PMA.

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

    ClinicalTrials.gov

    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

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

    ClinicalTrials.gov

    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

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

    PubMed Central

    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

  4. Identification of high versus lower risk clinical subgroups in a group of adult patients with supratentorial anaplastic astrocytomas.

    PubMed

    Decaestecker, C; Salmon, I; Camby, I; Dewitte, O; Pasteels, J L; Brotchi, J; Van Ham, P; Kiss, R

    1995-05-01

    The present work investigates whether computer-assisted techniques can contribute any significant information to the characterization of astrocytic tumor aggressiveness. Two complementary computer-assisted methods were used. The first method made use of the digital image analysis of Feulgen-stained nuclei, making it possible to compute 15 morphonuclear and 8 nuclear DNA content-related (ploidy level) parameters. The second method enabled the most discriminatory parameters to be determined. This second method is the Decision Tree technique, which forms part of the Supervised Learning Algorithms. These two techniques were applied to a series of 250 supratentorial astrocytic tumors of the adult. This series included 39 low-grade (astrocytomas, AST) and 211 high-grade (47 anaplastic astrocytomas, ANA, and 164 glioblastomas, GBM) astrocytic tumors. The results show that some AST, ANA and GBM did not fit within simple logical rules. These "complex" cases were labeled NC-AST, NC-ANA and NC-GBM because they were "non-classical" (NC) with respect to their cytological features. An analysis of survival data revealed that the patients with NC-GBM had the same survival period as patients with GBM. In sharp contrast, patients with ANA survived significantly longer than patients with NC-ANA. In fact, the patients with ANA had the same survival period as patients who died from AST, while the patients with NC-ANA had a survival period similar to those with GBM. All these data show that the computer-assisted techniques used in this study can actually provide the pathologist with significant information on the characterization of astrocytic tumor aggressiveness.

  5. [Adolescent and Young Adults (AYAS) brain tumor national Web conference. On behalf of ANOCEF, GO-AJA and SFCE societies].

    PubMed

    Frappaz, Didier; Sunyach, Marie-Pierre; Le Rhun, Emilie; Blonski, Marie; Laurence, Valérie; Bonneville Levard, Alice; Loiseau, Hugues; Meyronnet, David; Callies, Arnaud; Laigle-Donadey, F; Faure Conter, Cecile

    2016-12-01

    The skills of adult versus pediatric neuro-oncologists are not completely similar though additive. Because the tumors and their protocols are different and the tolerance and expected sequelae are specific. Multidisciplinary meetings including adult and pediatric neuro-oncologists are warranted to share expertise. Since 2008, a weekly national web based conference was held in France. Any patient with the following criteria could be discussed: Adolescent and Young Adults aged between 15 and 25 years, and any adult with a pediatric type pathology, including medulloblastoma, germ cell tumors, embryonic tumors, ependymoma, pilocytic astrocytoma.

  6. 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

    ClinicalTrials.gov

    2016-10-10

    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

  7. The molecular biology of WHO grade I astrocytomas.

    PubMed

    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.

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

    ClinicalTrials.gov

    2016-10-19

    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

  9. Pilomyxoid astrocytoma with involvement of the sella turcica in an adolescent.

    PubMed

    Alimohamadi, Maysam; Bidabadi, Mohammad Shirani; Ayan, Zahra; Ketabchi, Ebrahim; Amirjamshidi, Abbas

    2009-12-01

    Pilomyxoid astrocytoma (PMA) is a recently described tumor typically occurring in the hypothalamic-chiasmatic region of very young children. PMA is characterized by a more aggressive course than pilocytic astrocytoma and exhibits certain differing histological features. We report a PMA in an adolescent patient with visual field disturbance. Imaging studies revealed enlargement of the sella turcica due to a homogenously enhancing sellar and suprasellar mass identifiable both on CT scans and MRI. We believe that PMA may be included in the list of differential diagnoses of the lesions expanding the sella turcica.

  10. Hemiparesis after Operation of Astrocytoma Grade II in Adults: Effects of Acupuncture on Sensory-Motor Behavior and Quality of Life

    PubMed Central

    Yu, Haibo; Schröder, Sven; Li, Zhifeng; Yang, Ying; Chen, Yu; Huang, Xingxian

    2013-01-01

    To evaluate the effect of acupuncture on hemiparesis and quality of life for adults with brain astrocytoma grade II, we conducted a randomized, observer-blinded clinical trial. Fifty-eight patients were randomized to standard rehabilitation (SR) therapy without acupuncture (n = 20), SR plus standard acupuncture (SA) (n = 19), and SR plus individualized acupuncture (IA) (n = 19). SA points were PC6, SP6, HT1, LU5, BL40, and ST36, while a special concept called “connecting and regulation Ren and Du” and “Jin-3-needling” served as IA. This treatment was individualized according to the clinical syndrome. The outcome was measured by the Barthel Index (BI), the Fugl-Meyer scale (FM), and the EORTC Core Quality of Life Questionnaire (QLQ-C30) with the Brain Cancer Module (BCM20). IA + SR reached significantly higher BI scores than SA + SR, which reached significantly higher BI scores than SR. IA + SR was significantly superior to SA + SR and to SR at the 8th week for the scores of FM motor and sensory assessments and most QLQ-C30-BCM20 items. In conclusion, the individualized acupuncture concept of “connecting and regulating Ren and Du” combined with “Jin-3-needling” offers a promising possibility for the treatment of hemiparesis due to astrocytoma, but further evaluation is mandatory. PMID:23864900

  11. Promoter Methylation of RASSF1A Associates to Adult Secondary Glioblastomas and Pediatric Glioblastomas

    PubMed Central

    Muñoz, Jorge; Inda, María del Mar; Lázcoz, Paula; Zazpe, Idoya; Fan, Xing; Alfaro, Jorge; Tuñón, Teresa; Rey, Juan A.; Castresana, Javier S.

    2012-01-01

    While allelic losses and mutations of tumor suppressor genes implicated in the etiology of astrocytoma have been widely assessed, the role of epigenetics is still a matter of study. We analyzed the frequency of promoter hypermethylation by methylation-specific PCR (MSP) in five tumor suppressor genes (PTEN, MGMT, RASSF1A, p14ARF, and p16INK4A), in astrocytoma samples and cell lines. RASSF1A was the most frequently hypermethylated gene in all grades of astrocytoma samples, in cell lines, and in adult secondary GBM. It was followed by MGMT. PTEN showed a slight methylation signal in only one GBM and one pilocytic astrocytoma, and in two cell lines; while p14ARF and p16INK4A did not show any evidence of methylation in primary tumors or cell lines. In pediatric GBM, RASSF1A was again the most frequently altered gene, followed by MGMT; PTEN, p14 and p16 showed no alterations. Lack or reduced expression of RASSF1A in cell lines was correlated with the presence of methylation. RASSF1A promoter hypermethylation might be used as a diagnostic marker for secondary GBM and pediatric GBM. Promoter hypermethylation might not be an important inactivation mechanism in other genes like PTEN, p14ARF and p16INK4A, in which other alterations (mutations, homozygous deletions) are prevalent. PMID:22389839

  12. Patterns of practice and survival in a retrospective analysis of 1722 adult astrocytoma patients treated between 1985 and 2001 in 12 Italian radiation oncology centers

    SciTech Connect

    Magrini, Stefano Maria . E-mail: magrini@med.unibs.it; Ricardi, Umberto; Santoni, Riccardo; Krengli, Marco; Lupattelli, Marco; Cafaro, Ines; Scoccianti, Silvia; Menichelli, Claudia; Bertoni, Filippo; Enrici, Riccardo Maurizi; Tombolini, Vincenzo; Buglione, Michela; Pirtoli, Luigi

    2006-07-01

    Purpose: To analyze the patterns of practice and survival in a series of 1722 adult astrocytoma patients treated in 12 Italian radiotherapy centers. Methods and Materials: A total of 1722 patients were treated with postoperative radiotherapy (90% World Health Organization [WHO] Grade 3-4, 62% male, 44% aged >60 years, 25% with severe neurologic deficits, 44% after gross total resection, 52% with high-dose radiotherapy, and 16% with chemotherapy). Variations in the clinical-therapeutic features in three subsequent periods (1985 through 2001) were evaluated, along with overall survival for the different subgroups. Results: The proportion of women, of older patients, of those with worse neurologic performance status (NPS), with WHO Grade 4, and with smaller tumors increased with time, as did the proportion of those treated with radical surgery, hypofractionated radiotherapy, and more sophisticated radiotherapy techniques, after staging procedures progressively became more accurate. The main prognostic factors for overall survival were age, sex, neurologic performance status, WHO grade, extent of surgery, and radiation dose. Conclusions: Recently, broader selection criteria for radiotherapy were adopted, together with simpler techniques, smaller total doses, and larger fraction sizes for the worse prognostic categories. Younger, fit patients are treated more aggressively, more often in association with chemotherapy. Survival did not change over time. The accurate evaluation of neurologic status is therefore of utmost importance before the best treatment option for the individual patient is chosen.

  13. Clinico-pathological feature of pilomyxoid astrocytomas: three case reports.

    PubMed

    Nagaishi, Masaya; Yokoo, Hideaki; Hirato, Junko; Yoshimoto, Yuhei; Nakazato, Yoichi

    2011-04-01

    Pilomyxoid astrocytoma (PMA) is a newly identified variant of pilocytic astrocytoma (PA). We report three cases of PMA with comparison to seven cases of PA in terms of their clinicopathological features. The three cases occurred at the ages of 2, 36 and 6 years, and their tumors were located in the left basal ganglia, the pineal gland, and the cerebellum, respectively. They were diagnosed PMA by surgical specimens that showed a characteristic monomorphous architecture with an angiocentric growth pattern and myxoid background. One patient developed localized relapse at 6 months after the surgery, but the other patients remained alive without tumor progression more than 5 years after treatment. In analysis of the immunohistochemical association in PMA and PA, no specific staining was found to be useful for differential diagnosis of PMA from PA. The expression of biomarkers including O-6-methylguanine-DNA methyltransferase, p53, MIB-1, and EGF receptor neither distinguished PMA from PA nor correlated with outcome. But almost all PMA and PA that demonstrated prominent positivity for nestin showed a high MIB-1 labelling index (LI), and four of these five patients suffered a relapse in the early phase. These results suggest that immunohistochemical expression of nestin and MIB-1 LI may correlate with the aggressiveness of the tumor in PA and PMA.

  14. IDH1 Mutations Are Early Events in the Development of Astrocytomas and Oligodendrogliomas

    PubMed Central

    Watanabe, Takuya; Nobusawa, Sumihito; Kleihues, Paul; Ohgaki, Hiroko

    2009-01-01

    IDH1 encodes isocitrate dehydrogenase 1, which participates in the citric acid cycle and was recently reported to be mutated in 12% of glioblastomas. We assessed IDH1 mutations in 321 gliomas of various histological types and biological behaviors. A total of 130 IDH1 mutations was detected, and all were located at amino acid residue 132. Of these, 91% were G→A mutations (Arg→His). IDH1 mutations were frequent in low-grade diffuse astrocytomas (88%) and in secondary glioblastomas that developed through progression from low-grade diffuse or anaplastic astrocytoma (82%). Similarly, high frequencies of IDH1 mutations were found in oligodendrogliomas (79%) and oligoastrocytomas (94%). Analyses of multiple biopsies from the same patient (51 cases) showed that there were no cases in which an IDH1 mutation occurred after the acquisition of either a TP53 mutation or loss of 1p/19q, suggesting that IDH1 mutations are very early events in gliomagenesis and may affect a common glial precursor cell population. IDH1 mutations were co-present with TP53 mutations in 63% of low-grade diffuse astrocytomas and with loss of heterozygosity 1p/19q in 64% of oligodendrogliomas; they were rare in pilocytic astrocytomas (10%) and primary glioblastomas (5%) and absent in ependymomas. The frequent presence of IDH1 mutations in secondary glioblastomas and their near-complete absence in primary glioblastomas reinforce the concept that despite their histological similarities, these subtypes are genetically and clinically distinct entities. PMID:19246647

  15. Reduced TSC2 RNA and protein in sporadic astrocytomas and ependymomas.

    PubMed

    Wienecke, R; Guha, A; Maize, J C; Heideman, R L; DeClue, J E; Gutmann, D H

    1997-08-01

    Individuals affected with tuberous sclerosis complex (TSC) develop several benign and malignant tumors at increased frequency, including astrocytomas. Tuberin, the protein product of the tuberous sclerosis complex-2 (TSC2) tumor suppressor gene, has been shown to directly inhibit cell growth and is expressed at high levels in normal central nervous system neurons and astrocytes. To determine whether TSC2 RNA and protein are reduced in astrocytomas from individuals without tuberous sclerosis, reverse transcriptase-polymerase chain reaction and immunoblotting analyses were performed on 49 adult astrocytomas, 10 pediatric astrocytomas, and 13 ependymomas. Eighteen of 40 (45%) high-grade (World Health Organization [WHO] grade III/IV) astrocytomas and 4 of 8 (50%) adult low-grade (WHO grade II) astrocytomas demonstrated reduced or absent TSC2 expression, including 1 giant cell astrocytoma, whereas none of the 10 pediatric low-grade astrocytomas analyzed showed a reduction in TSC2 expression. Reduced or absent tuberin was observed in 2 of 6 (33%) ependymomas analyzed. These data demonstrate, for the first time, that reduced or absent TSC2 expression may represent one of the critical genetic events associated with the development of sporadic adult, but not pediatric, astrocytomas.

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

    PubMed

    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

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

    PubMed Central

    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

  18. ATRX and IDH1-R132H immunohistochemistry with subsequent copy number analysis and IDH sequencing as a basis for an "integrated" diagnostic approach for adult astrocytoma, oligodendroglioma and glioblastoma.

    PubMed

    Reuss, David E; Sahm, Felix; Schrimpf, Daniel; Wiestler, Benedikt; Capper, David; Koelsche, Christian; Schweizer, Leonille; Korshunov, Andrey; Jones, David T W; Hovestadt, Volker; Mittelbronn, Michel; Schittenhelm, Jens; Herold-Mende, Christel; Unterberg, Andreas; Platten, Michael; Weller, Michael; Wick, Wolfgang; Pfister, Stefan M; von Deimling, Andreas

    2015-01-01

    Diffuse gliomas are represented in the 2007 WHO classification as astrocytomas, oligoastrocytomas and oligodendrogliomas of grades II and III and glioblastomas WHO grade IV. Molecular data on these tumors have a major impact on prognosis and therapy of the patients. Consequently, the inclusion of molecular parameters in the WHO definition of brain tumors is being planned and has been forwarded as the "ISN-Haarlem" consensus. We, here, analyze markers of special interest including ATRX, IDH and 1p/19q codeletion in a series of 405 adult patients. Among the WHO 2007 classified tumors were 152 astrocytomas, 61 oligodendrogliomas, 63 oligoastrocytomas and 129 glioblastomas. Following the concepts of the "ISN-Haarlem", we rediagnosed the series to obtain "integrated" diagnoses with 155 tumors being astrocytomas, 100 oligodendrogliomas and 150 glioblastomas. In a subset of 100 diffuse gliomas from the NOA-04 trial with long-term follow-up data available, the "integrated" diagnosis had a significantly greater prognostic power for overall and progression-free survival compared to WHO 2007. Based on the "integrated" diagnoses, loss of ATRX expression was close to being mutually exclusive to 1p/19q codeletion, with only 2 of 167 ATRX-negative tumors exhibiting 1p/19q codeletion. All but 4 of 141 patients with loss of ATRX expression and diffuse glioma carried either IDH1 or IDH2 mutations. Interestingly, the majority of glioblastoma patients with loss of ATRX expression but no IDH mutations exhibited an H3F3A mutation. Further, all patients with 1p/19 codeletion carried a mutation in IDH1 or IDH2. We present an algorithm based on stepwise analysis with initial immunohistochemistry for ATRX and IDH1-R132H followed by 1p/19q analysis followed by IDH sequencing which reduces the number of molecular analyses and which has a far better association with patient outcome than WHO 2007.

  19. Positron Emission Tomography Using Fluorine F 18 EF5 to Find Oxygen in Tumor Cells of Patients Who Are Undergoing Surgery or Biopsy for Newly Diagnosed Brain Tumors

    ClinicalTrials.gov

    2013-01-15

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Central Nervous System Germ Cell Tumor; 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 Grade III Meningioma; Adult Medulloblastoma; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Pilocytic Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Subependymoma; Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Meningeal Melanocytoma

  20. Endoscopic disconnection of hypothalamic astrocytoma causing gelastic epilepsy. Case report.

    PubMed

    Park, Young Seok; Lee, Yun Ho; Shim, Kyu-Won; Kim, Dong-Seok; Lee, Joon Soo; Kim, Heung Dong

    2009-08-01

    The authors report on a case of juvenile pilocytic astrocytoma (JPA) and concomitant hypothalamic hamartoma (HH) with gelastic epilepsy that was successfully treated with endoscopic disconnection. This 6-year-old girl presented with prolonged, medically intractable gelastic seizures that were often followed by generalized tonic seizures. An enhancing, low-grade hypothalamic tumor was identified on MR images obtained when she was 11 months old, but no surgical intervention was attempted at that time apart from bur hole drainage of a chronic subdural hemorrhage. In the first surgery, performed when she was 6 years of age, the authors attempted disconnection and tumor sampling; the lesion was revealed to be a JPA. A second endoscopic disconnection was performed 1 year later to improve seizure control and obtain a pathological specimen from the nonenhancing contralateral side. The pathological results after the second surgery revealed that the enhancing mass was a spontaneously regressing JPA and the contralateral nonenhancing mass was an HH. The HH was found as latent tumor and the JPA was the mass causing gelastic epilepsy. To the authors' knowledge, this is the first report of a patient with a spontaneously regressing JPA and concomitant HH, both of which were treated by endoscopic disconnection.

  1. RO4929097, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Malignant Glioma

    ClinicalTrials.gov

    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

  2. 18F-FDOPA PET/CT or PET/MRI in Measuring Tumors in Patients With Newly-Diagnosed or Recurrent Gliomas

    ClinicalTrials.gov

    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

  3. Natural history and management of brainstem gliomas in adults. A retrospective Italian study.

    PubMed

    Salmaggi, A; Fariselli, L; Milanesi, I; Lamperti, E; Silvani, A; Bizzi, A; Maccagnano, E; Trevisan, E; Laguzzi, E; Rudà, R; Boiardi, A; Soffietti, R

    2008-02-01

    Brainstem gliomas in adults are rare tumors, with heterogeneous clinical course; only a few studies in the MRI era describe the features in consistent groups of patients. In this retrospective study, we report clinical features at onset, imaging characteristics and subsequent course in a group of 34 adult patients with either histologically proven or clinico-radiologically diagnosed brainstem gliomas followed at two centers in Northern Italy. Of the patients 18 were male, 14 female, with a median age of 31. In 21 of the patients histology was obtained and in 20 it was informative (2 pilocytic astrocytoma, 9 low-grade astrocytoma, 8 anaplastic astrocytoma and 1 glioblastoma). Contrast enhancement at MRI was present in 14 patients. In all of the 9 patients who were investigated with MR spectroscopy, the Cho/NAA ratio was elevated at diagnosis. In 8 of the patients, an initial watch and wait policy was adopted, while 24 were treated shortly after diagnosis with either radiotherapy alone [4] or radiotherapy and chemotherapy [20] (mostly temozolomide). Only minor radiological responses were observed after treatments; in a significant proportion of patients (9 out of 15) clinical improvement during therapy occurred in the context of radiologically (MRI) stable disease. Grade III or IV myelotoxicity was observed in 6 patients. After a follow-up ranging from 9 to 180 months, all but 2 patients have progressed and 14 have died (12 for disease progression, 2 for pulmonary embolism). Median overall survival time was of 59 months. Investigation of putative prognostically relevant parameters showed that a short time between disease onset and diagnosis was related to a shorter survival. Compared with literature data, our study confirms the clinical and radiological heterogeneity of adult brainstem gliomas and underscores the need for multicenter trials in order to assess the efficacy of treatments in these tumors.

  4. P17.41CLINICAL MANAGEMENT AND OUTCOME OF HISTOLOGICALLY VERIFIED ADULT BRAINSTEM GLIOMAS IN SWITZERLAND: A RETROSPECTIVE ANALYSIS OF 21 PATIENTS

    PubMed Central

    Hundsberger, T.; Tonder, M.; Andreas, H.; Brügge, D.; Roelcke, U.; Putora, P.M.; Stupp, R.; Weller, M.

    2014-01-01

    BACKGROUND: Because of low incidence, mixed study populations and paucity of clinical and histological data, the management of adult brainstem gliomas remains non-standardized. We here describe characteristics, treatment and outcome of patients with exclusively histologically confirmed adult brainstem gliomas. METHODS: A retrospective chart review of adults (>age 18 years) was conducted. Brainstem glioma was defined as a glial tumor located in the midbrain, pons or medulla. Characteristics, management and outcome were analyzed. RESULTS: 21 patients (17 males; median age 41 years) were diagnosed between 2004 and 2012 by biopsy (n = 15), partial (n = 4) or complete resection (n = 2). Diagnoses were glioblastoma (WHO grade IV, n = 6), anaplastic astrocytoma (WHO grade III, n = 7), diffuse astrocytoma (WHO grade II, n = 6) and pilocytic astrocytoma (WHO grade I, n = 2). Diffuse gliomas were mainly located in the pons and frequently showed MRI contrast enhancement. Endophytic growth was common (16 versus 5). Postoperative therapy in low-grade (WHO grade I/II) and high-grade gliomas (WHO grade III/IV) consisted of radiotherapy alone (3 in each group), radiochemotherapy (2 versus 6), chemotherapy alone (0 versus 2) or no postoperative therapy (3 versus 1). Median PFS (24.1 versus 5.8 months; log-rank, p = 0.009) and mOS (30.5 versus 11.5 months; log-rank, p = 0.028) was significantly better in WHO grade II than in WHO grade III/IV tumors. Second-line therapy considerably varied. CONCLUSIONS: Histologically verification of adult brainstem glioma is feasible and has an impact on postoperative treatment. Low-grade gliomas can simple be followed or treated with radiotherapy alone. Radiochemotherapy with temozolomide can safely be prescribed for high-grade gliomas without additional CNS toxicities.

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

    PubMed

    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.

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

    SciTech Connect

    Yamaguchi, F.; Saya, H.; Bruner, J.M.; Morrison, R.S. )

    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.

  7. Cystic cerebellar astrocytomas in childhood.

    PubMed

    Griffin, T W; Beaufait, D; Blasko, J C

    1979-07-01

    Thirty-nine patients with low grade cystic cerebellar astrocytomas were treated at the University of Washington and Children's Orthopedic Hospital in Seattle, Washington, between 1955 and 1977; 29 were treated with partial or complete resection alone, and 10 received radiation therapy after various types of surgical procedures. With a mean follow-up time of 7 years, the survival rate for patients who had complete resections of their primary disease was 100%. The relapse-free survival rate was 82%. The relapse-free survival rate for patients treated primarily with partial resection alone was 36%. Postoperative irradiation after partial resection for both primary and recurrent disease resulted in a relapse-free survival rate of 83%. If complete tumor excision is not possible, postoperative radiation therapy is recommended following partial resection.

  8. Frontal lobe astrocytoma following radiotherapy for medulloblastoma

    SciTech Connect

    Cohen, M.S.; Kushner, M.J.; Dell, S.

    1981-05-01

    A young woman had a frontal lobe astrocytoma 14 years after successful treatment of a posterior fossa medulloblastoma by surgery and whole-neuraxis irradiation. The association of these two tumors is rare, and it is unlikely that the second tumor was the result of metastasis and differentiation of residual or recurrent medulloblastoma. We review the evidence supporting this view and also the likelihood that the astrocytoma was induced by the prior radiation.

  9. Mitotic recombination of chromosome 17 in astrocytomas

    SciTech Connect

    James, C.D.; Carlbom, E.; Nordenskjold, M.; Collins, V.P.; Cavenee, W.K. )

    1989-04-01

    Allelic combinations at seven loci on human chromosome 17 defined by restriction fragment length polymorphisms were determined in tumor and normal tissues from 35 patients with gliomas. Loss of constitutional heterozygosity at one or more of these loci was observed in 8 of the 24 tumors displaying astrocytic differentiation and in the single primitive neuroectodermal tumor examined. The astrocytomas showing these losses included examples of each adult malignancy grade of the disease, including glioblastoma (malignancy grade IV), and seven of them demonstrated concurrent maintenance of heterozygosity for at least one chromosome 17 locus. Determination of allele dosage together with the genotypic data indicated that the tumor chromosomes 17 were derived by mitotic recombination in 7 of the 9 cases with shared homozygosity of the region 17p11.2-ptr in all cases. In contrast, tumors of oligodendrocytic, ependymal, or mixed cellular differentiation did not exhibit loss of alleles at any of the loci examined. These data suggest that the somatic attainment of homozygosity for loci on chromosome 17p is frequently associated with the oncogenesis of central nervous system tumors, particularly those showing solely astrocytic differentiation, and that mitotic recombination mapping is a useful approach towards the subregional localization of a locus whose rearrangement is involved in this disease.

  10. Astrocytoma with involvement of medulla oblongata, spinal cord and spinal nerves in a raccoon (Procyon lotor)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Neoplasms affecting the central and peripheral nervous systems of wild animals are extremely rare. Described are clinical signs, pathologic and immunohistochemical findings in an adult female raccoon (Procyon lotor) with an astrocytoma which involved brainstem, cervical spinal cord and roots of the ...

  11. Spinal cord astrocytoma mimicking multifocal myelitis

    PubMed Central

    Neutel, Dulce; Teodoro, Tiago; Coelho, Miguel; Pimentel, José; Albuquerque, Luísa

    2014-01-01

    Introduction Differential diagnosis of acute/subacute intrinsic spinal cord lesions can be challenging. In addition, intramedullary neoplasms typically show gadolinium enhancement, mass effect, and cord expansion. Case report We report a patient with spinal cord and brain stem lesions resembling multifocal myelitis. Magnetic resonance imaging showed no spinal cord enlargement or gadolinium enhancing. Treatment of myelitis was undertaken without stopping the progression of the disease. Biopsy was made and led to a histological diagnosis of astrocytoma. Discussion Astrocytoma must remain as a possible diagnosis of spinal cord lesions, even without typical characteristics of neoplasms. Furthermore, biopsy should always be considered when diagnosis is uncertain. PMID:24621037

  12. BRAF V600E-mutated diffuse glioma in an adult patient: a case report and review.

    PubMed

    Suzuki, Yuta; Takahashi-Fujigasaki, Junko; Akasaki, Yasuharu; Matsushima, Satoshi; Mori, Ryosuke; Karagiozov, Kostadin; Joki, Tatsuhiro; Ikeuchi, Satoshi; Ikegami, Masahiro; Manome, Yoshinobu; Murayama, Yuichi

    2016-01-01

    Recent advances in genomic technology and genome-wide analysis have identified key molecular alterations that are relevant to the diagnosis and prognosis of brain tumors. Molecular information such as mutations in isocitrate dehydrogenase (IDH) genes or 1p/19q co-deletion status will be more actively incorporated into the histological classification of diffuse gliomas. BRAF V600E mutations are found frequently in circumscribed low-grade gliomas such as pleomorphic xanthoastrocytoma (PXA) and extra-cerebellar pilocytic astrocytoma, or epithelioid glioblastomas (E-GBM), a rare variant of GBM. This mutation is relatively rare in other types of diffuse gliomas, especially in adult onset cases. Here, we present an adult onset case of IDH wild-type/BRAF V600E-mutated diffuse glioma, evolving from grade III to grade IV. The tumor displayed atypical exophytic growth and had unusual histological features not fully compatible with, but indicative of PXA and E-GBM. We discuss differential diagnosis of the tumor, and review previously described diffuse gliomas with the BRAF V600E mutation.

  13. Bilateral Birdshot Retinochoroiditis and Retinal Astrocytoma

    PubMed Central

    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. Anaplastic astrocytoma mimicking herpes simplex encephalitis in 13-year old girl.

    PubMed

    Talathi, Saurabh; Gupta, Neha; Reddivalla, Naresh; Prokhorov, Sergey; Gold, Menachem

    2015-11-01

    Astrocytoma is the most common childhood brain tumor. Anaplastic astrocytoma (AA) are high grade gliomas (HGG), found very rarely in pediatric patients. AA mainly results from a dedifferentiation of a low grade astrocytoma. Clinical features of supra-tentorial tumors vary according to their anatomic location, biologic aggressiveness and age of the patient. They can be either completely asymptomatic or present with signs of raised intracranial pressure, seizures (about 40% of cases), behavior changes, speech disorders, declining school performance, or hemiparesis. There have been published adult cases of brain tumor misdiagnosed as viral encephalitis. Due to variety of clinical presentations, diagnosis of AA can be challenging. Here we report a case of a 13 year old girl who presented with clinical features suggestive of viral encephalitis, such as fever, headache, dizziness, and first seizure with postictal sleep and prolonged drowsiness. However, her brain MRI findings were consistent with long standing mass effect from the underlying intracranial contents and that coupled with her history of unusual taste led to further investigations and the diagnosis of the AA. In retrospect, this presentation could have been a temporal epileptic aura. High grade astrocytomas are particularly difficult to treat with a two-year survival rates range from 10% to 30%. The treatment is multimodal with gross total surgical resection of the tumor, followed by radiotherapy with or without nitrosourea-containing chemotherapy regimen. Recent promising results seen with the use of temozolamide in adults has not been yet demonstrated in the pediatric patients. The extent of tumor resection remains the most significant indicator of survival and early recognition of this tumor is essential. This case report emphasizes the fact that mass lesions in the temporal lobe, including high-grade astrocytoma, should be considered in the differential diagnosis of suspected herpes simplex encephalitis

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

    ClinicalTrials.gov

    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

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

    PubMed Central

    Aaberg-Jessen, Charlotte; Hermansen, Simon K.; Kristensen, Bjarne W.

    2017-01-01

    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 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 expression in tumor cells and blood vessels. Measurements of MMP-2 intensity increased with tumor grade, and MMP-2 expression was found to be significantly higher in glioblastomas compared to normal brain tissue (p<0.001), diffuse astrocytomas (p<0.001) and anaplastic astrocytomas (p<0.05). MMP-2 expression was associated with shorter overall survival in patients with grade II-IV astrocytic tumors (HR 1.60; 95% CI 1.03–2.48; p = 0.036). In glioblastoma, high MMP-2 was associated with poorer prognosis in patients who survived longer than 8.5 months independent of age and gender (HR 2.27; 95% CI 1.07–4.81; p = 0.033). We found a positive correlation between MMP-2 and tissue inhibitor of metalloproteinases-1 (TIMP-1), and combined MMP-2 and TIMP-1 had stronger prognostic value than MMP-2 alone also when adjusting for age and gender (HR 2.78; 95% CI 1.30–5.92; p = 0.008). These findings were validated in bioinformatics databases. In conclusion, this study indicates that MMP-2 is associated with aggressiveness in astrocytomas and may hold an unfavorable prognostic value in

  17. Young Australian adults with NF1 have poor access to health care, high complication rates, and limited disease knowledge.

    PubMed

    Oates, Emily C; Payne, Jonathan M; Foster, Sheryl L; Clarke, Nigel F; North, Kathryn N

    2013-04-01

    Neurofibromatosis type 1 (NF1) is a multisystem disease associated with a lifelong risk of debilitating and potentially life-limiting complications, however many adults with NF1 have no regular health surveillance. We interviewed and examined 17 young adults with NF1 between the ages of 25 and 33. Most had not been assessed for NF1-related complications within the previous 8 years, including patients with known serious vascular complications, for example, renal artery stenosis. Acute and/or chronic pain, particularly back and plexiform-related pain were common symptoms, and despite a significant impact on quality of life, was untreated in most instances. Symptom and examination-directed imaging revealed serious complications in 41% of the cohort. These included severe spinal cord compression (two cases), a highly SUV avid lesion suggestive of malignancy (one case), and a Juvenile Pilocytic Astrocytoma in a patient without any previous NF1-related complications. Few study participants had a good understanding of NF1, its associated risks and complications, and many had not sought appropriate medical advice as questions or problems arose. NF1-related cognitive deficits in some participants, and the lack of a clear source of expert medical advice for adults with NF1 likely contributed to poor health surveillance and management in this population. Overall, these findings suggest that many Australian adults with NF1 are at risk of serious and life-threatening medical complications, but are not accessing and receiving adequate health care. Access to multidisciplinary adult clinics that specialize in NF1 may address many of the unmet health needs of young adults with NF1.

  18. Copy Number Profiling of Brazilian Astrocytomas

    PubMed Central

    Bidinotto, Lucas Tadeu; Torrieri, Raul; Mackay, Alan; Almeida, Gisele Caravina; Viana-Pereira, Marta; Cruvinel-Carloni, Adriana; Spina, Maria Luisa; Campanella, Nathalia Cristina; Pereira de Menezes, Weder; Clara, Carlos Afonso; Becker, Aline Paixão; Jones, Chris; Reis, Rui Manuel

    2016-01-01

    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. PMID:27172220

  19. An Achilles tendinosis masking an intramedullary astrocytoma.

    PubMed

    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.

  20. Fast neutrons and misonidazole for malignant astrocytomas

    SciTech Connect

    Kurup, P.D.; Pajak, T.F.; Hendrickson, F.R.; Nelson, J.S.; Mansell, J.; Cohen, L.; Awschalom, M.; Rosenberg, I.; Ten Haken, R.K.

    1985-04-01

    Twenty-five patients with proven malignant supratentorial astrocytomas were entered into a Phase I/II study of misonidazole combined with neutron radiation at Fermilab Neutron Therapy Facility (NTF) between August 1979 and April 1981. The main objectives were to determine tissue tolerance in terms of acute and late effects, and to estimate tumor clearance and survival rates. The total dose was 18.0 Gy given in weekly fractions of 3.0 Gy over 39 days. Four hours before each irradiation, 2.5 gm/m/sup 2/ misonidazole was administered orally. The median survival for the whole group was 12.0 months; 25% were alive at 18 months with some neurological compromise. Acute toxicity was within tolerable limits. Details of toxicity and tissue analysis from post mortems and second craniotomy samples are presented.

  1. P06SUPRATENTORIAL PNET IN ADULTS: MRI CAN HELP DISTINGUISH FROM GLIOBLASTOMA - DWI IS KEY

    PubMed Central

    Eralil, George; Jones, Timothy L.; Howe, Franklyn A.; Barrick, Tom R.; MacKinnon, Andrew D.

    2014-01-01

    INTRODUCTION: Extra-pineal supratentorial primitive neuro-ectodermal tumours (sPNETs) are considered rare in adults and little is known about their radiological appearances. The most clinically relevant pre-surgical differential diagnosis is glioblastoma multiforme (GBM). We present a series of patients with sPNET over a 6 year period (2008-2014), and provide an imaging update with a review of the existing literature. METHOD: Retrospective review of CT and MRI characteristics of 7 patients with histologically proven sPNETs. Comparisons were made with similarly located and histopathologically confirmed WHO Grade 4 GBMs. RESULTS: 6 of the 7 sPNETs occurred de novo. One arose within the resection bed of a WHO Grade 1 pilocytic astrocytoma. There were 4 frontal and 3 temporal lobe incidences. Mean age was 42.8yrs (range 23 - 73 yrs, median 36 yrs). On CT the solid component of the tumour was usually hyperdense. Some of the small sPNETs contained central haemorrhage, confirmed on MRI. Larger tumours were solid/cystic. On MRI the solid component of all sPNETs was T2 hypointense, showed avid enhancement and marked restricted diffusion, typical of a high grade tumour. The degree of restricted diffusion was notably greater in the sPNET group when compared to the GBM cohort. CONCLUSION: The extreme rarity of sPNETs in adults makes for difficult interpretation of existing imaging modalities. In non-histopathologically confirmed cases, imaging could be misinterpreted as high grade glioma. However, greater restricted diffusion in sPNETs may help distinguish them from GBMs. Advanced MRI techniques and correlation with spectroscopy and molecular markers will also help in the future.

  2. Pre-irradiation chemotherapy for newly diagnosed high grade astrocytoma.

    PubMed

    Mathieu, N Tubiana; Genet, D; Labrousse, F; Bouillet, P; Denes, S Lavau; Martin, J; Labourey, J L; Venat, L; Clavere, P; Moreau, J J

    2004-01-01

    The purpose of this work was to determine the response rate and toxicity of a combination of Carmustine and Cisplatin administered before radiation in patients with newly diagnosed high grade astrocytoma. A good response rate has been published with this association in primary cerebral high grade tumor. This protocol was administered in a homogeneous population of 37 adult patients with measurable tumor on magnetic resonance imaging (MRI) or CT scan. After biopsy or subtotal resection, the patients received BCNU 40 mg/m2/d and CODP 40 mg/m2/d, for 3 days every 28 days for 3 cycles. Evaluation was performed before each cycle. Radiation therapy began 4 weeks after completing the chemotherapy or immediately if there was evidence of tumor progression on chemotherapy. Seven out of 37 (19%) demonstrated tumor regression with a median duration to progression of 11 months. Median survival was 6 months. Myelosuppression was the predominant but manageable toxicity. This work indicated that the first chemotherapy protocol gave poor results in a homogeneous group of patients, with bad prognosis.

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

    PubMed

    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

  4. KIAA1549-BRAF fusions and IDH mutations can coexist in diffuse gliomas of adults.

    PubMed

    Badiali, Manuela; Gleize, Vincent; Paris, Sophie; Moi, Loredana; Elhouadani, Selma; Arcella, Antonietta; Morace, Roberta; Antonelli, Manila; Buttarelli, Francesca Romana; Figarella-Branger, Dominique; Kim, Young-Ho; Ohgaki, Hiroko; Mokhtari, Karima; Sanson, Marc; Giangaspero, Felice

    2012-11-01

    KIAA1549-BRAF fusion gene and isocitrate dehydrogenase (IDH) mutations are considered two mutually exclusive genetic events in pilocytic astrocytomas and diffuse gliomas, respectively. We investigated the presence of the KIAA1549-BRAF fusion gene in conjunction with IDH mutations and 1p/19q loss in 185 adult diffuse gliomas. Moreover BRAF(v600E) mutation was also screened. The KIAA1549-BRAF fusion gene was evaluated by reverse-transcription polymerase chain reaction (RT-PCR) and sequencing. We found IDH mutations in 125 out 175 cases (71.4%). There were KIAA1549-BRAF fusion gene in 17 out of 180 (9.4%) cases and BRAF(v600E) in 2 out of 133 (1.5%) cases. In 11 of these 17 cases, both IDH mutations and the KIAA1549-BRAF fusion were present, as independent molecular events. Moreover, 6 of 17 cases showed co-presence of 1p/19q loss, IDH mutations and KIAA1549-BRAF fusion. Among the 17 cases with KIAA1549-BRAF fusion gene 15 (88.2%) were oligodendroglial neoplasms. Similarly, the two cases with BRAF(v600E) mutation were both oligodendroglioma and one had IDH mutations and 1p/19q co-deletion. Our results suggest that in a small fraction of diffuse gliomas, KIAA1549-BRAF fusion gene and BRAF(v600E) mutation may be responsible for deregulation of the Ras-RAF-ERK signaling pathway. Such alterations are more frequent in oligodendroglial neoplasm and may be co-present with IDH mutations and 1p/19q loss.

  5. Telomerase activity in human brain tumors: astrocytoma and meningioma.

    PubMed

    Kheirollahi, Majid; Mehrazin, Masoud; Kamalian, Naser; Mohammadi-asl, Javad; Mehdipour, Parvin

    2013-05-01

    Somatic cells do not have telomerase activity but immortalized cell lines and more than 85 % of the cancer cells show telomerase activation to prevent the telomere from progressive shortening. The activation of this enzyme has been found in a variety of human tumors and tumor-derived cell lines, but only few studies on telomerase activity in human brain tumors have been reported. Here, we evaluated telomerase activity in different grades of human astrocytoma and meningioma brain tumors. In this study, assay for telomerase activity performed on 50 eligible cases consisted of 26 meningioma, 24 astrocytoma according to the standard protocols. In the brain tissues, telomerase activity was positive in 39 (65 %) of 50 patients. One sample t test showed that the telomerase activity in meningioma and astrocytoma tumors was significantly positive entirely (P < 0.001). Also, grade I of meningioma and low grades of astrocytoma (grades I and II) significantly showed telomerase activity. According to our results, we suggest that activation of telomerase is an event that starts mostly at low grades of brain including meningioma and astrocytoma tumors.

  6. Effects of dexamethasone on C6 astrocytoma radiosensitivity

    SciTech Connect

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

    1989-05-01

    Brain-tumor patients often undergo radiation therapy while receiving corticosteroids for the treatment of cerebral edema. Studies have demonstrated that dexamethasone is radioprotective in a number of cell lines. The C6 astrocytoma cell line is well established in vitro and is modulated by dexamethasone treatment. It has therefore been hypothesized that dexamethasone-treated C6 astrocytoma cells would be more resistant to radiation-induced damage. The present study was carried out to assess this hypothesis using both the in vitro C6 astrocytoma monolayer and three-dimensional multicellular spheroid models. Dexamethasone was inhibitory to the C6 astrocytoma cells in the monolayer preparation, increasing their doubling time by 13%. In the spheroid cultures, dexamethasone treatment decreased the number of cells per spheroid by 46%. Dexamethasone did not affect the plating efficiency of either the cells from the monolayer experiment or those dissociated from spheroids, however, suggesting that the inhibitory effect was not tumoricidal. At a clinical concentration (1.94 x 10(-5) M), dexamethasone did not significantly influence plating efficiency of irradiated C6 astrocytoma cells in monolayer or three-dimensional spheroid cultures.

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

    PubMed

    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; Unterberg, Andreas; Platten, Michael; Wick, Wolfgang; Herold-Mende, Christel; Aldape, Kenneth; von Deimling, Andreas

    2015-06-01

    The WHO 2007 classification of tumors of the CNS distinguishes between diffuse astrocytoma WHO grade II (A II(WHO2007)) 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 far, classification and grading relies on morphological grounds only and does not yet take into account IDH status, a molecular marker of prognostic relevance. We here demonstrate that WHO 2007 grading performs poorly in predicting prognosis when applied to astrocytoma carrying IDH mutations. Three independent series including a total of 1360 adult diffuse astrocytic gliomas with IDH mutation containing 683 A II(IDHmut), 562 AA III(IDHmut) and 115 GBM(IDHmut) have been examined for age distribution and survival. In all three series patients with A II(IDHmut )and AA III(IDHmut) were of identical age at presentation of disease (36-37 years) and the difference in survival between grades was much less (10.9 years for A II(IDHmut), 9.3 years for AA III(IDHmut)) than that reported for A II(WHO2007) versus AA III(WHO2007). Our analyses imply that the differences in age and survival between A II(WHO2007) and AA III(WHO2007) predominantly depend on the fraction of IDH-non-mutant astrocytomas in the cohort. This data poses a substantial challenge for the current practice of astrocytoma grading and risk stratification and is likely to have far-reaching consequences on the management of patients with IDH-mutant astrocytoma.

  8. Alterations of the RRAS and ERCC1 genes at 19q13 in gemistocytic astrocytomas.

    PubMed

    Ohta, Takashi; Kim, Young-Ho; Oh, Ji-Eun; Satomi, Kaishi; Nonoguchi, Naosuke; Keyvani, Kathy; Pierscianek, Daniela; Sure, Ulrich; Mittelbronn, Michel; Paulus, Werner; Vital, Anne; Yokoo, Hideaki; McDonald, Kerrie; Kleihues, Paul; Nazaret, Nicolas; Barbet, Fabienne; Lachuer, Joel; Ohgaki, Hiroko

    2014-10-01

    Gemistocytic astrocytoma (World Health Organization grade II) is a rare variant of diffuse astrocytoma that is characterized by the presence of neoplastic gemistocytes and has a significantly less favorable prognosis. Other than frequent TP53 mutations (>80%), little is known about its molecular profile. Here, we show that gemistocytic astrocytomas carry a lower frequency of IDH mutations than fibrillary astrocytomas (74% vs 92%; p = 0.0255) but have profiles similar to those of fibrillary astrocytomas with respect to TERT promoter mutations (5% vs 0%), 1p/19q loss (10% vs 8%), and loss of heterozygosity 10q (10% vs 12%). Exome sequencing in 5 gemistocytic astrocytomas revealed homozygous deletion of genes at 19q13 (i.e. RRAS [related RAS viral oncogene homolog; 2 cases] and ERCC1 [excision repair cross-complementing rodent repair deficiency, complementation group 1; 1 case]). Further screening showed RRAS homozygous deletion in 7 of 42 (17%) gemistocytic astrocytomas and in 3 of 24 (13%) IDH1 mutated secondary glioblastomas. Patients with gemistocytic astrocytoma and secondary glioblastoma with an RRAS deletion tended to have shorter survival rates than those without deletion. Differential polymerase chain reaction and methylation-specific polymerase chain reaction revealed an ERCC1 homozygous deletion or promoter methylation in 10 of 42 (24%) gemistocytic astrocytomas and in 8 of 24 (33%) secondary glioblastomas. Alterations in RRAS and ERCC1 appear to be typical in gemistocytic astrocytomas and secondary glioblastomas, since they were not present in 49 fibrillary astrocytomas or 30 primary glioblastomas.

  9. Novel Dual-Reporter Preclinical Screen for Anti-Astrocytoma Agents Identifies Cytostatic and Cytotoxic Compounds

    PubMed Central

    Hawes, Jessica J.; Nerva, John D.; Reilly, Karlyne M.

    2009-01-01

    Astrocytoma/glioblastoma is the most common malignant form of brain cancer and is often unresponsive to current pharmacological therapies and surgical interventions. Despite several potential therapeutic agents against astrocytoma and glioblastoma (1), there are currently no effective therapies for astrocytoma, creating a great need for the identification of effective anti-tumor agents. We have developed a novel dual-reporter system in Trp53/Nf1-null astrocytoma cells to simultaneously and rapidly assay cell viability and cell cycle progression as evidenced by activity of the human E2F1 promoter in vitro. The dual-reporter high-throughput assay was used to screen experimental therapeutics for activity in Trp53/Nf1-null astrocytoma. Several compounds were identified demonstrating selectivity for astrocytoma over primary astrocytes. The dual-reporter system described here may be a valuable tool for identifying potential anti-tumor treatments that specifically target astrocytoma. PMID:18664715

  10. Progesterone Induces the Growth and Infiltration of Human Astrocytoma Cells Implanted in the Cerebral Cortex of the Rat

    PubMed Central

    Germán-Castelán, Liliana; Manjarrez-Marmolejo, Joaquín; González-Arenas, Aliesha; González-Morán, María Genoveva; Camacho-Arroyo, Ignacio

    2014-01-01

    Progesterone (P4) promotes cell proliferation in several types of cancer, including brain tumors such as astrocytomas, the most common and aggressive primary intracerebral neoplasm in humans. In this work, we studied the effects of P4 and its intracellular receptor antagonist, RU486, on growth and infiltration of U373 cells derived from a human astrocytoma grade III, implanted in the motor cortex of adult male rats, using two treatment schemes. In the first one, fifteen days after cells implantation, rats were daily subcutaneously treated with vehicle (propylene glycol, 160 μL), P4 (1 mg), RU486 (5 mg), or P4 + RU486 (1 mg and 5 mg, resp.) for 21 days. In the second one, treatments started 8 weeks after cells implantation and lasted for 14 days. In both schemes we found that P4 significantly increased the tumor area as compared with the rest of the treatments, whereas RU486 blocked P4 effects. All rats treated with P4 showed tumor infiltration, while 28.6% and 42.9% of the animals treated with RU486 and P4 + RU486, respectively, presented it. Our data suggest that P4 promotes growth and migration of human astrocytoma cells implanted in the motor cortex of the rat through the interaction with its intracellular receptor. PMID:24982875

  11. Experience With Carbon Ion Radiotherapy for WHO Grade 2 Diffuse Astrocytomas

    SciTech Connect

    Hasegawa, Azusa; Mizoe, Jun-Etsu; Tsujii, Hirohiko; Kamada, Tadashi; Jingu, Keiichi; Iwadate, Yasuo; Nakazato, Youichi; Matsutani, Masao; Takakura, Kintomo

    2012-05-01

    Purpose: To assess outcomes of carbon ion radiotherapy for diffuse astrocytomas in adults. Methods and Materials: Between October 1994 and February 2002, 14 patients with diffuse astrocytoma, identified as eligible for carbon ion radiotherapy, were enrolled in a phase I/II clinical trial. Carbon ion radiotherapy was administered in 24 fractions over 6 weeks. The normal tissue morbidity was monitored carefully, and the carbon ion dose was escalated from 50.4 Gy equivalent (GyE) to 55.2 GyE. Patients were divided into two groups according to their carbon ion doses: a low-dose group in which 2 patients were irradiated with 46.2 GyE and 7 patients were irradiated with 50.4 GyE, and a high-dose group in which 5 patients were irradiated with 55.2 GyE. Results: Toxicities were within acceptable limits, and none of the patients developed Grade 3 or higher acute or late reactions. The median progression-free survival (PFS) time was 18 months for the low-dose group and 91 months for the high-dose group (p = 0.0030). The median overall survival (OS) time was 28 months for the low-dose group and not reached for the high-dose group (p = 0.0208). Conclusion: High-dose group patients showed significant improvement in PFS and OS rates compared to those in the low-dose group, and both dose groups showed acceptable toxicity.

  12. Involvement of the neural stem cell compartment by pediatric and adult gliomas: a retrospective review of 377 cases.

    PubMed

    Marsh, James C; Goldman, Stewart; Ziel, Ellis; Bregman, Corey; Diaz, Aidnag; Byrne, Richard; Fangusaro, Jason

    2015-03-01

    To assess frequency of neural stem cell compartment (NSC) involvement in adult and pediatric gliomas [World Health Organization (WHO) grades 1-4], and to assess whether NSC involvement at presentation impacts on survival, recurrence rates, and/or transformation from low grade (WHO grade 1-2) to high grade disease (WHO grades 3-4). Cranial MRIs for 154 pediatric and 223 adult glioma patients treated from 2000 to 2012 were reviewed. NSC involvement was documented. Tumors were stratified by age (adult vs. pediatric), histology, tumor grade, tumor location, and involvement of midline structures. Odds ratios (OR) for death were calculated based on NSC status at presentation. Rates of transformation and recurrence rates (ORR) were compared using Fisher's Exact Test. Time to recurrence (TTR) was calculated using student t test. Among recurrent and transformed tumors, we also assessed the rate of NSC involvement at time of recurrence or transformation. 74.8 % of tumors had NSC involvement. Higher rates of NSC involvement were seen among adult (p = .0001); high grade (p = .0001)); grade 2 versus grade 1 (p = .0001) and other grade 1 histologies (p = .0001) versus JPA (juvenile pilocytic astrocytoma) patients); grade 2-4 tumors (p = .0001); and supratentorial tumors (p < .0001). No transformation was noted among pediatric low grade tumors or adult grade 1 tumors. 22/119 (18.5 %) adult grade 2 tumors transformed. Rates of transformation were not impacted by NSC status (p = .47). ORR was 15.1 %, and was greater for NSC+ tumors at presentation (p = .05). 36/41 recurrences (87.8 %) involved NSC at time of recurrence. OR for death was 2.62 (1.16-5.9), p = .02 for NSC+ tumors at presentation. Adult and pediatric gliomas (all grades) frequently involve NSC at presentation, although rates are lower in pediatric JPA and all infratentorial tumors. NSC involvement at presentation increases OR death and reduces TTR for pediatric gliomas (all grades) and adult low grade gliomas, and

  13. Differential expression of Notch family members in astrocytomas and medulloblastomas.

    PubMed

    Xu, Peng; Yu, Shizhu; Jiang, Rongcai; Kang, Chunsheng; Wang, Guangxiu; Jiang, Hao; Pu, Peiyu

    2009-12-01

    Notch signaling pathway plays an integral role in determining cell fates in development. Growing evidence demonstrates that Notch signaling pathway has versatile effects in tumorigenesis depending on the tumor type, grade and stage. Notch signaling pathway is deregulated in some brain tumors. To examine the differential expression of Notch family members (Notch1, 2, 3, 4) in human astrocytomas and medulloblastomas, and to evaluate their roles in the development of both tumor types. Immunohistochemical staining and Western blot analysis were used to detect Notch1, 2, 3, 4 expression in tissue microarray and freshly resected tissue samples of normal brain, astrocytomas and medulloblastomas. Notch family members were not expressed or barely detectable in normal brain tissues. Notch1, 3, 4 were highly expressed but Notch2 was not expressed in astrocytomas. The percentage of immunopositive tumor cells and level of Notch1 expression was increased with tumor grade. In addition, overexpression of Notch2 was detected in medulloblastomas in contrast to low or no expression of Notch1, 3, 4. Differential expression of Notch1, 2, 3, 4 is detected in astrocytomas and medulloblastomas, that may be related to their different roles playing in the development of brain tumors.

  14. Immunohistochemical characterization of subependymal giant cell astrocytomas.

    PubMed

    Lopes, M B; Altermatt, H J; Scheithauer, B W; Shepherd, C W; VandenBerg, S R

    1996-01-01

    Subependymal giant cell astrocytoma (SEGA) is the most common neoplastic process involving the brain in patients with tuberous sclerosis complex (TSC). Morphologically, these tumors exhibit a wide range of cytoarchitecture with spindle and epithelioid cells resembling astrocytes, and also large, occasionally giant cells, some of which have a distinctly ganglion-like appearance. Unresolved questions regarding SEGAs center on: (a) their cytogenesis, i.e., whether they are derived from single or multiple precursors; and (b) their differentiating capacity along glial or neuronal lines. We sought to determine whether SEGAs represent truly mixed tumors or whether they consist of a single population of cells with a capacity for divergent differentiation. Twenty SEGAs were assessed for immunophenotypic features of either neuronal or glial differentiation or both. Only tumors from patients with a clinically confirmed diagnosis of TSC were included. Immunoreactivity for glial fibrillary acidic protein (GFAP) and/or S-100 protein was considered indicative of a glial phenotype, whereas the presence of neuronal differentiation was assessed by staining for cytoskeletal proteins [neurofilament epitopes, class III Beta-tubulin, microtubule-associated protein 2 (MAP2), synaptophysin], neurosecretory substances [serotonin, cholecystokinin, Beta-endorphin, substance P, somatostatin, metenkephalin, neuropeptide Y, vasoactive intestinal polypeptide (VIP), and for the 28-kDa neuron-associated calcium binding protein calbindin. Of the tumors examined, 18 exhibited both glial and neuronal epitopes, the staining pattern being variable. In 19 tumors, the constituent spindle, polygonal and giant or ganglion-like cells showed variable immunoreactivity for GFAP and S-100 proteins both within the cell body and processes. Neuron-associated cytoskeletal proteins were present in 18 cases. Class III Beta-tubulin immunoreactivity was demonstrated in 17 tumors, both within the bodies of all three

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

    PubMed

    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. Regression of grade III astrocytoma during the treatment of CML with imatinib mesylate.

    PubMed

    Jayawardena, Suriya; Sooriabalan, Danushan; Indulkar, Shalaka; Kim, Hyun Ho; Matin, Abu; Maini, Archana

    2006-01-01

    Astrocytomas are central nervous system neoplasms, which are derived predominately from astrocytes. On the basis of the histopathologic characteristics astrocytomas are graded from I to IV. The cells that demonstrate the greatest degree of anaplasia are used to determine the histologic grade of the tumor. The mean age of survival are approximately 10 years from the time of diagnosis for pilocystic astrocytomas (World Health Organization grade I), more than 5 years for patients with low-grade diffuse astrocytomas (WHO grade II), 2 to 5 years for those with anaplastic astrocytomas (WHO grade III), and less than 1 year for patients with glioblastoma (WHO grade IV). The treatment is a combination of surgery, radiation, and chemotherapy depending of the grade of astrocytoma. We present a case of 31-year-old man with grade III astrocytoma with subsequent chronic myelogenous leukemia treated with imatinib mesylate as part of his chronic myelogenous leukemia treatment failing to show recurrence of the astrocytoma 10 years after standard treatment for astrocytoma.

  17. Expression of aquaporin8 in human astrocytomas: Correlation with pathologic grade

    SciTech Connect

    Zhu, Shu-juan; Wang, Ke-jian; Gan, Sheng-wei; Xu, Jin; Xu, Shi-ye; Sun, Shan-quan

    2013-10-11

    Highlights: •AQP8 is mainly distributed in the cytoplasm of human astrocytoma cells. •AQP8 over-expressed in human astrocytomas, especially glioblastoma. •The up-regulation of AQP8 is related to the pathological grade of human astrocytomas. •AQP8 may contribute to the growth and proliferation of astrocytomas. -- Abstract: Aquaporin8 (AQP8), a member of the aquaporin (AQP) protein family, is weakly distributed in mammalian brains. Previous studies on AQP8 have focused mainly on the digestive and the reproductive systems. AQP8 has a pivotal role in keeping the fluid and electrolyte balance. In this study, we investigated the expression changes of AQP8 in 75 cases of human brain astrocytic tumors using immunohistochemistry, Western blotting, and reverse transcription polymerase chain reaction. The results demonstrated that AQP8 was mainly distributed in the cytoplasm of astrocytoma cells. The expression levels and immunoreactive score of AQP8 protein and mRNA increased in low-grade astrocytomas, and further increased in high-grade astrocytomas, especially in glioblastoma. Therefore, AQP8 may contribute to the proliferation of astrocytomas, and may be a biomarker and candidate therapy target for patients with astrocytomas.

  18. Expression of neonatal Nav1.5 in human brain astrocytoma and its effect on proliferation, invasion and apoptosis of astrocytoma cells.

    PubMed

    Xing, Deguang; Wang, Jun; Ou, Shaowu; Wang, Yunjie; Qiu, Bo; Ding, Daling; Guo, Feng; Gao, Qinghua

    2014-06-01

    In the present study, we designed and conducted a series of assays to determine the expression of voltage-gated sodium channel (VGSC) neonatal isoform Nav1.5 (nNav1.5) in human brain astrocytoma and its effect on the proliferation, migration, invasion and apoptosis of astrocytoma U251 cells. The results showed that nNav1.5 mRNA and protein were expressed in both human brain astrocytoma and normal brain tissues, but their expression levels in astrocytoma were significantly higher (P<0.05). In astrocytomas, nNav1.5 mRNA and protein levels were also different (P<0.05) and were correlated with pathological grades. The immunofluorescence confocal microscopy observations demonstrated that nNav1.5 protein was expressed in the nucleus, cytoplasm and membrane of the astrocytoma cells. After transfection, the small interfering RNA (siRNA) targeted to nNav1.5 significantly reduced the expression levels of SCN5A/nNav1.5 mRNA and protein by 57.2% (P<0.05) and 66.6% (P<0.05), respectively. The MTT, wound healing, Matrigel invasion and flow cytometric assays confirmed that following siRNA downregulation of the expression of the SCN5A/nNav1.5 gene, the in vitro proliferation and in vitro invasiveness of the U251 cells were significantly reduced (P<0.05 for both comparisons), and the apoptosis rate was significantly increased (P<0.05). These results revealed that nNav1.5 expression in human brain astrocytoma was upregulated, and its expression was positively correlated with the degree of malignancy. Additionally, reduced nNav1.5 expression significantly suppressed the proliferation and invasiveness of astrocytoma cells, indicating a new target in the molecular diagnosis and therapy of astrocytoma.

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

    PubMed

    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

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

    NASA Astrophysics Data System (ADS)

    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

  1. Management of Pediatric Spinal Cord Astrocytomas: Outcomes With Adjuvant Radiation

    SciTech Connect

    Guss, Zachary D.; Moningi, Shalini; Jallo, George I.; Cohen, Kenneth J.; Wharam, Moody D.; Terezakis, Stephanie A.

    2013-04-01

    Purpose: Pediatric intramedullary spinal cord tumors are exceedingly rare; in the United States, 100 to 200 cases are recognized annually, of these, most are astrocytomas. The purpose of this study is to report the outcomes in pediatric patients with spinal cord astrocytomas treated at a tertiary care center. Methods and Materials: An institutional review board-approved retrospective single-institution study was performed for pediatric patients with spinal cord astrocytomas treated at our hospital from 1990 to 2010. The patients were evaluated on the extent of resection, progression-free survival (PFS), and development of radiation-related toxicities. Kaplan-Meier curves and multivariate regression model methods were used for analysis. Results: Twenty-nine patients were included in the study, 24 with grade 1 or 2 (low-grade) tumors and 5 with grade 3 or 4 (high-grade) tumors. The median follow-up time was 55 months (range, 1-215 months) for patients with low-grade tumors and 17 months (range, 10-52 months) for those with high-grade tumors. Thirteen patients in the cohort received chemotherapy. All patients underwent at least 1 surgical resection. Twelve patients received radiation therapy to a median radiation dose of 47.5 Gy (range, 28.6-54.0 Gy). Fifteen patients with low-grade tumors and 1 patient with a high-grade tumor exhibited stable disease at the last follow-up visit. Acute toxicities of radiation therapy were low grade, whereas long-term sequelae were infrequent and manageable when they arose. All patients with low-grade tumors were alive at the last follow-up visit, compared with 1 patient with a high-grade tumor. Conclusion: Primary pediatric spinal cord astrocytomas vary widely in presentation and clinical course. Histopathologic grade remains a major prognostic factor. Patients with low-grade tumors tend to have excellent disease control and long-term survival compared to those with high-grade tumors. This experience suggests that radiation therapy

  2. Characterization of the blood brain barrier in pediatric central nervous system neoplasms

    PubMed Central

    Hong, Christopher S.; Ho, Winson; Piazza, Martin G.; Ray-Chaudhury, Abhik; Zhuang, Zhengping; Heiss, John D.

    2016-01-01

    Objective The normal blood–brain barrier (BBB) is composed of tight junctions between endothelial cells and surrounding astrocyte foot processes. Breakdown of the physiological astrocyte-endothelial cell relationship occurs in adult metastatic and primary brain tumors. However, the astrocyte-endothelial cell relationship has not been studied in pediatric tumors. Materials and Methods Utilizing specimens from cases of pilocytic astrocytoma (n = 5), medulloblastoma (n = 5), and low-grade diffuse astrocytoma (n = 1), immunofluorescence were performed using primary antibodies against CD31, glial fibrillary acidic protein (GFAP), and aquaporin 4 (AQ4). Clinical, magnetic resonance imaging, operative, and histopathological findings were analyzed. Results Strongly-enhancing areas of medulloblastoma exhibited complete BBB breakdown with sparse GFAP and AQ4 staining around CD31-positive vessels. Moderately enhancing regions of pilocytic astrocytomas exhibited regions of intact BBB and vasculature surrounded by dense GFAP staining but reduced and disorganized AQ4 staining, suggesting tumor cells could not fulfill physiological BBB support. Non-enhancing low-grade diffuse astrocytoma demonstrated intact BBB with intense peri-microvasculature GFAP and AQ4 staining. AQ4 stained so strongly that AQ4 visualization alone delineated CD31-positive vessels. Conclusion Taken together, BBB breakdown in pediatric tumors corresponds to a loss of normal endothelial cell-astrocyte foot process relationships. Further development of pharmaceutical agents capitalizing on this disrupted BBB is warranted in medulloblastoma and pilocytic astrocytoma. However, BBB integrity remains a challenge in treating low-grade diffuse astrocytoma before progression toward secondary glioblastoma. PMID:27917302

  3. The Use of Three Long Non-Coding RNAs as Potential Prognostic Indicators of Astrocytoma.

    PubMed

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

    2015-01-01

    Long noncoding RNAs (lncRNAs) are pervasively transcribed and play a key role in tumorigenesis. The aim of the study was to determine the lncRNA expression profile in astrocytomas and to assess its potential clinical value. We performed a three-step analysis to establish the lncRNA profile for astrocytoma: a) the lncRNA expression was examined on 3 astrocytomas as well as 3 NATs (normal adjacent tissues) using the lncRNA microarray; b) the top-hits were validated in 40 astrocytomas (WHO grade II-IV) by quantitative real time-PCR (qRT-PCR); c) the hits with significant differences were re-evaluated using qRT-PCR in 90 astrocytomas. Finally, 7 lncRNAs were found to have a significantly different expression profile in astrocytoma samples compared to the NAT samples. Unsupervised clustering analysis further revealed the potential of the 7-lncRNA profile to differentiate between tumors and NAT samples. The upregulation of ENST00000545440 and NR_002809 was associated with advanced clinical stages of astrocytoma. Using Kaplan-Meier survival analysis, we showed that the low expression of BC002811 or XLOC_010967, or the high expression of NR_002809 was significantly associated with poor patient survival. Moreover, Cox proportional hazard regression analysis revealed that this prognostic impact was independent of other clinicopathological factors. Our results indicate that the lncRNA profile may be a potential prognostic biomarker for the prediction of post-surgical outcomes.

  4. Expression of AT1 and AT2 angiotensin receptors in astrocytomas is associated with poor prognosis

    PubMed Central

    Arrieta, O; Pineda-Olvera, B; Guevara-Salazar, P; Hernández-Pedro, N; Morales-Espinosa, D; Cerón-Lizarraga, T L; González-De la Rosa, C H; Rembao, D; Segura-Pacheco, B; Sotelo, J

    2008-01-01

    Astrocytomas develop intense vascular proliferation, essential for tumour growth and invasiveness. Angiotensin II (ANGII) was initially described as a vasoconstrictor; recent studies have shown its participation in cellular proliferation, vascularisation, and apoptosis. We conducted a prospective study to evaluate the expression of ANGII receptors – AT1 and AT2 – and their relationship with prognosis. We studied 133 tumours from patients with diagnosis of astrocytoma who underwent surgery from 1997 to 2002. AT1 and AT2 were expressed in 52 and 44% of the tumours, respectively, when determined by both reverse transcriptase–polymerase chain reaction and immunohistochemistry. Ten per cent of low-grade astrocytomas were positive for AT1, whereas grade III and IV astrocytomas were positive in 67% (P<0.001). AT2 receptors were positive in 17% of low-grade astrocytomas and in 53% of high-grade astrocytomas (P=0.01). AT1-positive tumours showed higher cellular proliferation and vascular density. Patients with AT1-positive tumours had a lower survival rate than those with AT1-negative (P<0.001). No association to survival was found for AT2 in the multivariate analysis. Expression of AT1 and AT2 is associated with high grade of malignancy, increased cellular proliferation, and angiogenesis, and is thus related to poor prognosis. These findings suggest that ANGII receptors might be potential therapeutic targets for high-grade astrocytomas. PMID:18594540

  5. High expression of the stem cell marker nestin is an adverse prognostic factor in WHO grade II-III astrocytomas and oligoastrocytomas

    PubMed Central

    Hatanpaa, Kimmo J.; Foong, Chan; Raisanen, Jack M.; Oliver, Dwight; Hiemenz, Matthew C.; Burns, Dennis K.; White, Charles L.; Whitworth, L. Anthony; Mickey, Bruce; Stegner, Martha; Habib, Amyn A.; Fink, Karen; Maher, Elizabeth A.; Bachoo, Robert M.

    2015-01-01

    Infiltrating astrocytomas and oligoastrocytomas of low to anaplastic grade (WHO grades II and III), in spite of being associated with a wide range of clinical outcomes, can be difficult to subclassify and grade by the current histopathologic criteria. Unlike oligodendrogliomas and anaplastic oligodendrogliomas that can be identified by the 1p/19q codeletion and the more malignant glioblastomas (WHO grade IV astrocytomas) that can be diagnosed solely based on objective features on routine hematoxylin and eosin sections, no such objective criteria exist for the subclassification of grade II-III astrocytomas and oligoastrocytomas (A+OA II-III). In this study, we evaluated the prognostic and predictive value of the stem cell marker nestin in adult A+OA II-III (n=50) using immunohistochemistry and computer-assisted analysis on tissue microarrays. In addition, the correlation between nestin mRNA level and total survival was analyzed in the NCI Rembrandt database. The results showed that high nestin expression is a strong adverse prognostic factor for total survival (p=0.0004). The strength of the correlation was comparable to but independent of the isocitrate dehydrogenase 1/2 (IDH 1/2) mutation status. Histopathological grading and subclassification did not correlate significantly with outcome, although the interpretation of this finding is limited by the fact that grade III tumors were treated more aggressively than grade II tumors. These results suggest that nestin level and IDH 1/2 mutation status are strong prognostic features in A+OA II-III and possibly more helpful for treatment planning than routine histopathological variables such as oligodendroglial component (astrocytoma vs. oligoastrocytoma) and WHO grade (grade II vs. III). PMID:24519516

  6. High expression of the stem cell marker nestin is an adverse prognostic factor in WHO grade II-III astrocytomas and oligoastrocytomas.

    PubMed

    Hatanpaa, Kimmo J; Hu, Tianshen; Vemireddy, Vamsidhara; Foong, Chan; Raisanen, Jack M; Oliver, Dwight; Hiemenz, Matthew C; Burns, Dennis K; White, Charles L; Whitworth, L Anthony; Mickey, Bruce; Stegner, Martha; Habib, Amyn A; Fink, Karen; Maher, Elizabeth A; Bachoo, Robert M

    2014-03-01

    Infiltrating astrocytomas and oligoastrocytomas of low to anaplastic grade (WHO grades II and III), in spite of being associated with a wide range of clinical outcomes, can be difficult to subclassify and grade by the current histopathologic criteria. Unlike oligodendrogliomas and anaplastic oligodendrogliomas that can be identified by the 1p/19q codeletion and the more malignant glioblastomas (WHO grade IV astrocytomas) that can be diagnosed solely based on objective features on routine hematoxylin and eosin sections, no such objective criteria exist for the subclassification of grade II-III astrocytomas and oligoastrocytomas (A+OA II-III). In this study, we evaluated the prognostic and predictive value of the stem cell marker nestin in adult A+OA II-III (n = 50) using immunohistochemistry and computer-assisted analysis on tissue microarrays. In addition, the correlation between nestin mRNA level and total survival was analyzed in the NCI Rembrandt database. The results showed that high nestin expression is a strong adverse prognostic factor for total survival (p = 0.0004). The strength of the correlation was comparable to but independent of the isocitrate dehydrogenase 1/2 (IDH 1/2) mutation status. Histopathological grading and subclassification did not correlate significantly with outcome, although the interpretation of this finding is limited by the fact that grade III tumors were treated more aggressively than grade II tumors. These results suggest that nestin level and IDH 1/2 mutation status are strong prognostic features in A+OA II-III and possibly more helpful for treatment planning than routine histopathological variables such as oligodendroglial component (astrocytoma vs. oligoastrocytoma) and WHO grade (grade II vs. III).

  7. Ki-67 immunostaining in astrocytomas: Association with histopathological grade – A South Indian study

    PubMed Central

    Shivaprasad, Nandish Vastrad; Satish, Suchitha; Ravishankar, Sunila; Vimalambike, Manjunath Gubbi

    2016-01-01

    Background: Astrocytomas are the most common primary tumor of the central nervous system. The distinction between different tumor grades can be tested despite criteria given by the World Health Organization (WHO). Ki-67 is a potent biological marker used in grading of astrocytomas, which estimates growth of the neoplasm quantitatively and will help in predicting prognosis accurately. Objectives: The aim of this was to study the proliferative activity using Ki-67 immunostaining and to assess the relationship of Ki-67 staining with the histopathological grading of astrocytomas. Patients and Methods: Thirty cases of histologically proven astrocytomas were studied. The histopathological grade was assessed using the 2007 WHO criteria. Immunohistochemistry for Ki-67 was done on paraffin-embedded wax sections. P < 0.05 was considered statistically significant. Results: Thirty cases of astrocytomas studied showed a male preponderance (M:F = 1.72:1) with a mean age of 48.1 years. Of these, Grade I, (n = 1, 3.33%), Grade II, (n = 7, 23.3%), Grade III (n = 6, 20%), and Grade IV (n = 16, 53.3%) astrocytomas were analyzed. The mean Ki-67 labeling index (LI) in Grades I, II, III, and IV was 0.02, 0.81, 9.14, and 17.81, respectively. Statistically significant difference was seen in the Ki-67 LI of low-grade (Grade II) and high-grade astrocytomas (Grades III and IV). There was concordance between histopathological grading and Ki-67 LI in 27 (90%) and discordance in 3 (10%) cases. Conclusion: Ki-67 LI varies considerably in different grades of astrocytomas and considerable overlaps can be observed between them. It can be of great help in situations where there is a lack of correlation between clinical parameters and histopathological diagnosis. Determination of Ki-67 LI should constitute a part of routine investigations in patients with astrocytomas. PMID:27695229

  8. Medium-grade astrocytoma in a cougar (Puma concolor).

    PubMed

    Kondo, Hirotaka; Leone, Angelique M; Erlacher-Reid, Claire; Gary, Joy; Kiupel, Matti; Farina, Lisa L; Abbott, Jeffrey R

    2012-12-01

    A 17-year-old, male castrated cougar (Puma concolor) was presented minimally responsive and severely depressed, with bilateral mydriasis and absent pupillary light response. On gross examination of the brain, there was a tan-to-gray, invasive mass with a central cavitation on the ventral aspect in the left cerebral hemisphere, rostral to the caudate nucleus. On histopathologic examination, the mass was composed of sheets of medium-sized, round-to-polygonal cells that were multifocally separated by islands of neuropil. Approximately 80% of the neoplastic cells showed strong cytoplasmic labeling for glial fibrillary acidic protein. These findings were consistent with a medium-grade astrocytoma. To the authors' knowledge, neoplastic disease of the central nervous system has not been previously reported in cougars.

  9. 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.

    PubMed

    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.

  10. Proliferating cell nuclear antigen, p53 and micro vessel density: Grade II vs. Grade III astrocytoma.

    PubMed

    Malhan, Priya; Husain, Nuzhat; Bhalla, Shalini; Gupta, Rakesh K; Husain, Mazhar

    2010-01-01

    Histological classification and grading are prime procedures in the management of patients with astrocytoma, providing vital data for therapeutic decision making and prognostication. However, it has limitations in assessing biological tumor behavior. This can be overcome by using newer immunohistochemical techniques. This study was carried out to compare proliferative indices using proliferating cell nuclear antigen (PCNA), extent of p53 expression and micro vessel morphometric parameters in patients with low grade and anaplastic astrocytoma. Twenty-five patients, each of grade II and grade III astrocytoma were evaluated using monoclonal antibodies to PCNA, p53 protein and factor VIII related antigen. PCNA, p53-labeling indices were calculated along with micro vessel morphometric analysis using Biovis Image plus Software. Patients with grade III astrocytoma had higher PCNA and p53 labeling indices as compared with grade II astrocytoma (29.14 plus/minus 9.87% vs. 16.84 plus/minus 6.57%, p 0.001; 18.18 plus/minus 6.14% vs. 6.14 plus/minus 7.23%, p 0.001, respectively). Micro vessel percentage area of patients with grade III astrocytoma was also (4.26 plus/minus 3.70 vs. 1.05 plus/minus 0.56, p 0.001), higher along with other micro vessel morphometric parameters. Discordance between histology and one or more IHC parameters was seen in 5/25 (20%) of patients with grade III astrocytoma and 9/25 (36%) of patients with grade II disease. PCNA and p53 labeling indices were positively correlated with Pearson's correlation, p less than 0.001 for both). Increased proliferative fraction, genetic alterations and neovascularization mark biological aggressiveness in astrocytoma. Immunohistochemical evaluation scores over meet the challenge of accurate prognostication of this potentially fatal malignancy.

  11. The expression of moesin in astrocytoma: correlation with pathologic grade and poor clinical outcome.

    PubMed

    Wu, Ming; Liu, Ding-Yang; Yuan, Xian-Rui; Liu, Qing; Jiang, Xin-Jun; Yuan, Dun; Huang, Jun; Li, Xue-Jun; Yang, Zhi-Quan

    2013-03-01

    Moesin, a member of the ERM family, acts as a linker between the actin cytoskeleton and the plasma membrane and plays a key role in the control of cell morphology, motility, adhesion and other processes of tumourigenesis. The expression pattern and clinical significance of moesin in astrocytoma remain unknown. In this study, we used RT-PCR to systematically investigate the expression of moesin in 49 astrocytomas of different pathological grade and 6 normal brain tissues. We found that the mRNA expression levels of moesin in astrocytomas were significantly higher in comparison with normal brain tissues. Furthermore, moesin up-regulation was correlated with pathological grade of astrocytomas. Subsequently, we tested 112 astrocytomas and 14 normal brain tissues by immunohistochemistry. Similar results were also confirmed. Univariate and multivariate survival analysis were used to determine the correlations of moesin expression with overall survival and progression-free survival. Our results showed the expression of moesin was strongly negatively correlated with the patient progression-free survival and overall survival. These results suggest moesin protein involved in the genesis and progression of astrocytomas and might be regarded as an independent predictor of poor prognosis.

  12. VRK2 identifies a subgroup of primary high-grade astrocytomas with a better prognosis

    PubMed Central

    2013-01-01

    Background Malignant astrocytomas are the most common primary brain tumors and one of the most lethal among human cancers despite optimal treatment. Therefore, the characterization of molecular alterations underlying the aggressive behavior of these tumors and the identification of new markers are thus an important step towards a better patient stratification and management. Methods and results VRK1 and VRK2 (Vaccinia-related kinase-1, -2) expression, as well as proliferation markers, were determined in a tissue microarray containing 105 primary astrocytoma biopsies. Kaplan Meier and Cox models were used to find clinical and/or molecular parameters related to overall survival. The effects of VRK protein levels on proliferation were determined in astrocytoma cell lines. High levels of both protein kinases, VRK1 or VRK2, correlated with proliferation markers, p63 or ki67. There was no correlation with p53, reflecting the disruption of the VRK-p53-DRAM autoregulatory loop as a consequence of p53 mutations. High VRK2 protein levels identified a subgroup of astrocytomas that had a significant improvement in survival. The potential effect of VRK2 was studied by analyzing the growth characteristics of astrocytoma cell lines with different EGFR/VRK2 protein ratios. Conclusion High levels of VRK2 resulted in a lower growth rate suggesting these cells are more indolent. In high-grade astrocytomas, VRK2 expression constitutes a good prognostic marker for patient survival. PMID:24079673

  13. Sulforhodamine 101 selectively labels human astrocytoma cells in an animal model of glioblastoma.

    PubMed

    Georges, Joseph F; Martirosyan, Nikolay L; Eschbacher, Jennifer; Nichols, Joshua; Tissot, Maya; Preul, Mark C; Feuerstein, Burt; Anderson, Trent; Spetzler, Robert F; Nakaji, Peter

    2014-05-01

    Sulforhodamine 101 (SR101) is a useful tool for immediate staining of astrocytes. We hypothesized that if the selectivity of SR101was maintained in astrocytoma cells, it could prove useful for glioma research. Cultured astrocytoma cells and acute slices from orthotopic human glioma (n=9) and lymphoma (n=6) xenografts were incubated with SR101 and imaged with confocal microscopy. A subset of slices (n=18) were counter-immunostained with glial fibrillary acidic protein and CD20 for stereological assessment of SR101 co-localization. SR101 differentiated astrocytic tumor cells from lymphoma cells. In acute slices, SR101 labeled 86.50% (±1.86; p<0.0001) of astrocytoma cells and 2.19% (±0.47; p<0.0001) of lymphoma cells. SR101-labeled astrocytoma cells had a distinct morphology when compared with in vivo astrocytes. Immediate imaging of human astrocytoma cells in vitro and in ex vivo rodent xenograft tissue labeled with SR101 can identify astrocytic tumor cells and help visualize the tumor margin. These features are useful in studying astrocytoma in the laboratory and may have clinical applications.

  14. Pre-B-cell leukemia homeobox interacting protein 1 is overexpressed in astrocytoma and promotes tumor cell growth and migration

    PubMed Central

    van Vuurden, Dannis G.; Aronica, Eleonora; Hulleman, Esther; Wedekind, Laurine E.; Biesmans, Dennis; Malekzadeh, Arjan; Bugiani, Marianna; Geerts, Dirk; Noske, David P.; Vandertop, W. Peter; Kaspers, Gertjan J.L.; Cloos, Jacqueline; Würdinger, Thomas; van der Stoop, Petra P.M.

    2014-01-01

    Background Glial brain tumors cause considerable mortality and morbidity in children and adults. Innovative targets for therapy are needed to improve survival and reduce long-term sequelae. The aim of this study was to find a candidate tumor-promoting protein, abundantly expressed in tumor cells but not in normal brain tissues, as a potential target for therapy. Methods In silico proteomics and genomics, immunohistochemistry, and immunofluorescence microscopy validation were performed. RNA interference was used to ascertain the functional role of the overexpressed candidate target protein. Results In silico proteomics and genomics revealed pre-B-cell leukemia homeobox (PBX) interacting protein 1 (PBXIP1) overexpression in adult and childhood high-grade glioma and ependymoma compared with normal brain. PBXIP1 is a PBX-family interacting microtubule-binding protein with a putative role in migration and proliferation of cancer cells. Immunohistochemical studies in glial tumors validated PBXIP1 expression in astrocytoma and ependymoma but not in oligodendroglioma. RNAi-mediated PBXIP1-knockdown in glioblastoma cell lines strongly reduced proliferation and migration and induced morphological changes, indicating that PBXIP1 knockdown decreases glioma cell viability and motility through rearrangements of the actin cytoskeleton. Furthermore, expression of PBXIP1 was observed in radial glia and astrocytic progenitor cells in human fetal tissues, suggesting that PBXIP1 is an astroglial progenitor cell marker during human embryonic development. Conclusion PBXIP1 is a novel protein overexpressed in astrocytoma and ependymoma, involved in tumor cell proliferation and migration, that warrants further exploration as a novel therapeutic target in these tumors. PMID:24470547

  15. Roles of the functional loss of p53 and other genes in astrocytoma tumorigenesis and progression.

    PubMed Central

    Nozaki, M.; Tada, M.; Kobayashi, H.; Zhang, C. L.; Sawamura, Y.; Abe, H.; Ishii, N.; Van Meir, E. G.

    1999-01-01

    Loss of function of the p53 tumor suppressor gene due to mutation occurs early in astrocytoma tumorigenesis in about 30-40% of cases. This is believed to confer a growth advantage to the cells, allowing them to clonally expand due to loss of the p53-controlled G1 checkpoint and apoptosis. Genetic instability due to the impaired ability of p53 to mediate DNA damage repair further facilitates the acquisition of new genetic abnormalities, leading to malignant progression of an astrocytoma into anaplastic astrocytoma. This is reflected by a high rate of p53 mutation (60-70%) in anaplastic astrocytomas. The cell cycle control gets further compromised in astrocytoma by alterations in one of the G1/S transition control genes, either loss of the p16/CDKN2 or RB genes or amplification of the cyclin D gene. The final progression process leading to glioblastoma multiforme seems to need additional genetic abnormalities in the long arm of chromosome 10; one of which is deletion and/or functional loss of the PTEN/MMAC1 gene. Glioblastomas also occur as primary (de novo) lesions in patients of older age, without p53 gene loss but with amplification of the epidermal growth factor receptor (EGFR) genes. In contrast to the secondary glioblastomas that evolve from astrocytoma cells with p53 mutations in younger patients, primary glioblastomas seem to be resistant to radiation therapy and thus show a poorer prognosis. The evaluation and design of therapeutic modalities aimed at preventing malignant progression of astrocytomas and glioblastomas should now be based on stratifying patients with astrocytic tumors according to their genetic diagnosis. PMID:11550308

  16. Relationship between CacyBP/SIP expression and prognosis in astrocytoma.

    PubMed

    Zhao, Wei; Wang, Chunlin; Wang, Junyu; Ge, Aiqing; Li, Yiming; Li, Weiqing; Lu, Yicheng

    2011-09-01

    The aim of this study was to investigate the expression of calcyclin-binding protein (also known as Siah-1-interacting protein [CacyBP/SIP]) in astrocytoma and to determine its prognostic value in overall survival of patients with glioblastoma multiforme (GBM). Tissue specimens were obtained from 77 Chinese patients who had undergone surgery for astrocytoma. The expression of CacyBP/SIP was examined by immunohistochemistry. The relationship between CacyBP/SIP and proliferating cell nuclear antigen index (PCNA) expression was investigated, and the prognostic value of CacyBP/SIP expression in patients with astrocytomas was analyzed. Of 77 tumors, 49 (63.6%) were negative for CacyBP/SIP expression. Loss of CacyBP/SIP expression was significantly associated with a high histological grade and with poor survival in univariate and multivariate analyses. Cox multivariable analysis showed that loss of CacyBP/SIP expression correlated with poor prognosis in patients with astrocytomas and was an independent prognostic factor (p<0.05). The mean survival time of patients with tumors that had lost expression of CacyBP/SIP was 25.58months (95% confidence interval [CI], 15.36-25.81months), compared to a mean survival time of 36.37months (95% CI, 27.90-44.84months) for patients with CacyBP/SIP-expressing tumors. CacyBP/SIP expression was also negatively correlated with PCNA expression in astrocytoma tissue (p<0.05). Our findings suggest that CacyBP/SIP may have an important role as a negative regulator of astrocytoma development and progression, and that CacyBP/SIP might be a useful molecular marker for predicting the prognosis of astrocytoma.

  17. Expression of endothelial nitric oxide synthase and vascular endothelial growth factor in association with neovascularization in human primary astrocytoma*

    PubMed Central

    Pan, Jian-wei; Zhan, Ren-ya; Tong, Ying; Zhou, Yong-qing; Zhang, Ming

    2005-01-01

    Objective: To investigate the relationship between the expression of endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF) and angiogenesis in primary astrocytoma. Methods: Thirty-seven primary astrocytomas and 4 astrocytic hyperplasia samples were collected and divided into three groups according to histological grade. The expression of eNOS, VEGF and factor VIII related antigen (FVIIIRAg) were assayed by immunohistochemistry. Microvascular density was assessed by FVIIIRAg immunoreactivity. The intensity of immunoreactivity was graded according to the percentage of positive tumor cells. Results: No eNOS and VEGF were expressed in the astrocytes and vascular endothelium in astrocytic hyperplasia. The expression of eNOS or VEGF was light in low-grade astrocytoma and strong in glioblastoma. eNOS expression in astrocytoma was very positively correlated with VEGF. eNOS and VEGF expression in anaplastic astrocytoma was median in contrast to the low grade astrocytoma and glioblastoma. Lower microvascular density was found in low grade astrocytoma than that in higher grade malignant ones. The expressions of eNOS and VEGF were correlated with microvascular density and tumor malignancy. Conclusion: This finding suggests that eNOS and VEGF may have cooperative effect in tumor angiogenesis and play an important role in the pathogenesis of primary astrocytoma. PMID:15973775

  18. Everolimus Treatment for an Early Infantile Subependymal Giant Cell Astrocytoma With Tuberous Sclerosis Complex.

    PubMed

    Fukumura, Shinobu; Watanabe, Toshihide; Takayama, Rumiko; Minagawa, Kimio; Tsutsumi, Hiroyuki

    2015-08-01

    Subependymal giant cell astrocytomas are benign tumors often observed with tuberous sclerosis complex. These tumors are rarely diagnosed during fetal life or early infancy. Until recently, the only available treatment has been surgical resection. Current clinical research has demonstrated that everolimus can induce these tumors' regression. We report a 19-month-old boy with tuberous sclerosis complex. At 2 months of age, he presented with congenital subependymal giant cell astrocytoma that was complicated by refractory epilepsy and severe mental retardation. Treatment with everolimus was started when he was 10 months old. Three months after initiating everolimus, the tumor was significantly reduced in size, and the reduction was subsequently maintained. His seizures decreased and he showed cognitive and developmental improvement. No severe adverse events have been observed to date. Everolimus has promise as an effective alternative to surgery for subependymal giant cell astrocytomas during early infancy.

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

    PubMed Central

    Tavares, Cléciton Braga; Gomes-Braga, Francisca das Chagas Sheyla Almeida; Costa-Silva, Danylo Rafhael; Escórcio-Dourado, Carla Solange; Borges, Umbelina Soares; Conde, Airton Mendes; da Conceição Barros-Oliveira, Maria; Sousa, Emerson Brandão; da Rocha Barros, Lorena; Martins, Luana Mota; Facina, Gil; da-Silva, Benedito Borges

    2016-01-01

    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. PMID:27626480

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

    PubMed Central

    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, P<0.01) and grade III (3.2-fold, P<0.05) astrocytoma, compared with controls. FMRP and Ki67 expressions were positively correlated (R2=0.877, P<0.001). Up-regulation of FMRP was associated with poorer survival among patients with FMRP integrated optical density >30 (P<0.01). In astrocytoma cell lines, FMRP knock-down slowed proliferation (P<0.05), inhibited total MEK levels P<0.05, and reduced phosphorylation of MEK (Ser217/221) and ERK (Thr202/Tyr204) (P<0.05). In mice with orthotopic tumors, FMRP knock-down decreased FMRP and Ki67 expressions, and reduced tumor volume and weight (36.3% or 61.5% on day 15, both P<0.01). Also, phosphorylation of MEK (Ser217/221) and ERK (Thr202/Tyr204), and total MEK in xenografts were decreased in sh-FMRP xenografts compared with non-transfected ones (all P<0.05). Conclusion Enhanced FMRP expression in astrocytoma may promote proliferation through activation of MEK/ERK signaling. PMID:27683117

  1. Sunitinib in Treating Patients With Recurrent Malignant Gliomas

    ClinicalTrials.gov

    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

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

    PubMed Central

    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.

  3. Expression of vascular endothelial growth factor-b in human astrocytoma.

    PubMed Central

    Gollmer, J. C.; Ladoux, A.; Gioanni, J.; Paquis, P.; Dubreuil, A.; Chatel, M.; Frelin, C.

    2000-01-01

    Growth of human malignant gliomas is stringently dependent on an angiogenic process that probably involves vascular endothelial growth factor (VEGF). Expressions of mRNA coding for the different forms of VEGF were analyzed in surgical specimens from human astrocytomas. Low levels of placental growth factor (PGF) and VEGFC mRNA were observed in polymerase chain reaction, but not in Northern blot experiments. VEGF mRNA was found in some but not all grade and grade IV astrocytomas. VEGFB mRNA was observed in all tissue samples analyzed irrespective of the tumor grade. A new splice variant of VEGFB (VEGFB155) that lacks exons 5 and 6 is described. Expressions of VEGF mRNA in cultured glioblastomas cells were upregulated by hypoxia, but the sensitivity of the cells to hypoxia was reduced as compared with normal rat astrocytes. VEGF expression was depressed by dexamethasone. Expressions of VEGFB mRNA were affected neither by hypoxia nor by dexamethasone. The results indicate a coexpression of VEGF mRNA and VEGFB mRNA in human astrocytomas. Expression of VEGFB is markedly different from that of VEGF. Possible roles of VEGFB as a cofactor for hypoxia-induced angiogenesis in human astrocytomas are discussed. PMID:11303624

  4. Impaired tooth root development after treatment of a cerebellar astrocytoma: A case report

    SciTech Connect

    Eckles, T.A.; Kalkwarf, K.L.

    1989-10-01

    A young man, previously treated by surgical resection of a grade III cerebellar astrocytoma in combination with irradiation and chemotherapy, was found to display severe generalized root agenesis. This patient also exhibited secondary hypothyroidism and decreased levels of growth hormone. These factors are discussed in relation to their possible role in impaired root development.

  5. Spatial orientation deficit in children due to cerebellum astrocytoma pediatric tumor obtained by means of the Attentional Network Test.

    PubMed

    Quintero-Gallego, E A; Gómez, C M; Morales, M; Márquez, J

    2011-10-31

    Cerebellum astrocytomas are the most typical nervous system tumors in children. Several cognitive deficits have been previously described. These deficits are probably produced by cerebellar connection and gray matter damage. The present study examines attentional deficits in children operated on for cerebellum astrocytomas, using an attentional paradigm with theoretical and clinical bases: the Attentional Network Test (ANT). This test was designed considering the attentional network theory proposed by Posner, and its usefulness has been demonstrated in clinical settings. Children operated on for cerebellar astrocytoma showed a mild attentional deficit in the orientation network.

  6. Exposure to ELF-pulse modulated X band microwaves increases in vitro human astrocytoma cell proliferation.

    PubMed

    Pérez-Castejón, C; Pérez-Bruzón, R N; Llorente, M; Pes, N; Lacasa, C; Figols, T; Lahoz, M; Maestú, C; Vera-Gil, A; Del Moral, A; Azanza, M J

    2009-12-01

    Common concern about the biological effects of electromagnetic fields (EMF) is increasing with the expansion of X-band microwaves (MW). The purpose of our work was to determine whether exposure to MW pulses in this range can induce toxic effects on human astrocytoma cells. Cultured astrocytoma cells (Clonetics line 1321N1) were submitted to 9.6 GHz carrier, 90% amplitude modulated by extremely low frequency (ELF)-EMF pulses inside a Gigahertz Transversal Electromagnetic Mode cell (GTEM-cell). Astrocytoma cultures were maintained inside a GTEM-incubator in standard culture conditions at 37+/-0.1 degrees C, 5% CO2, in a humidified atmosphere. Two experimental conditions were applied with field parameters respectively of: PW 100-120 ns; PRF 100-800 Hz; PRI 10-1.25 ms; power 0.34-0.60 mW; electric field strength 1.25-1.64 V/m; magnetic field peak amplitude 41.4-54.6 microOe. SAR was calculated to be 4.0 x 10-4 W/Kg. Astrocytoma samples were grown in a standard incubator. Reaching 70-80% confluence, cells were transferred to a GTEM-incubator. Experimental procedure included exposed human astrocytoma cells to MW for 15, 30, 60 min and 24 h and unexposed sham-control samples. Double blind method was applied. Our results showed that cytoskeleton proteins, cell morphology and viability were not modified. Statistically significant results showed increased cell proliferation rate under 24h MW exposure. Hsp-70 and Bcl-2 antiapoptotic proteins were observed in control and treated samples, while an increased expression of connexin 43 proteins was found in exposed samples. The implication of these results on increased proliferation is the subject of our current research.

  7. Is Upregulation of Aquaporin 4-M1 Isoform Responsible for the Loss of Typical Orthogonal Arrays of Particles in Astrocytomas?

    PubMed Central

    Fallier-Becker, Petra; Nieser, Maike; Wenzel, Ulrike; Ritz, Rainer; Noell, Susan

    2016-01-01

    The astrocytic endfoot membranes of the healthy blood-brain barrier—contacting the capillary—are covered with a large number of the water channel aquaporin 4 (AQP4). They form orthogonal arrays of particles (OAPs), which consist of AQP4 isoform M1 and M23. Under pathologic conditions, AQP4 is distributed over the whole cell and no or only small OAPs are found. From cell culture experiments, it is known that cells transfected only with AQP4-M1 do not form OAPs or only small ones. We hypothesized that in astrocytomas the situation may be comparable to the in vitro experiments expecting an upregulation of AQP4-M1. Quantitative Real-time PCR (qRT-PCR) of different graded astrocytomas revealed an upregulation of both isoforms AQP4 M1 and M23 in all astrocytomas investigated. In freeze fracture replicas of low-grade malignancy astrocytomas, more OAPs than in high-grade malignancy astrocytomas were found. In vitro, cultured glioma cells did not express AQP4, whereas healthy astrocytes revealed a slight upregulation of both isoforms and only a few OAPs in freeze fracture analysis. Taken together, we found a correlation between the decrease of OAPs and increasing grade of malignancy of astrocytomas but this was not consistent with an upregulation of AQP4-M1 in relation to AQP4 M23. PMID:27483250

  8. Cannabinoid and cannabinoid-like receptors in microglia, astrocytes and astrocytomas

    PubMed Central

    Stella, Nephi

    2010-01-01

    CB1 and CB2 receptors are activated by a plethora of cannabinoid compounds, be they endogenously-produced, plant-derived or synthetic. These receptors are expressed by microglia, astrocytes and astrocytomas, and their activation regulates these cells’ differentiation, functions and viability. Recent studies show that glial cells also express cannabinoid-like receptors, and that their activation regulates different cell functions, but also control cell viability. This review summarizes this evidence, and discusses how selective compounds targeting cannabinoid-like receptors constitute promising therapeutics to manage neuroinflammation and eradicate malignant astrocytomas. Importantly, the selective targeting of cannabinoid-like receptors should provide therapeutic relieve without inducing the typical psychotropic effects and possible addictive properties associated with the use of Δ9-tetrahydrocannabinol, the main psychotropic ingredient produced by the plant Cannabis sativa. PMID:20468046

  9. MicroRNA-542-3p Suppresses Tumor Cell Invasion via Targeting AKT Pathway in Human Astrocytoma*

    PubMed Central

    Cai, Junchao; Zhao, JingJing; Zhang, Nu; Xu, Xiaonan; Li, Rong; Yi, Yang; Fang, Lishan; Zhang, Le; Li, Mengfeng; Wu, Jueheng; Zhang, Heng

    2015-01-01

    The molecular mechanism underlying constitutive activation of AKT signaling, which plays essential roles in astrocytoma progression, is not fully characterized. Increasing numbers of studies have reported that microRNAs are involved in the malignant behavior of astrocytoma cells via directly targeting multiple oncogenes or tumor suppressors. Here, we found that microRNA (miR)-542-3p expression was decreased in glioblastoma cell lines and astrocytoma tissues, and reduced levels of miR-542-3p expression correlated with high histopathological grades and poor prognosis of astrocytoma patients. Exogenous miR-542-3p suppressed glioblastoma cell invasion through not only targeting AKT1 itself but also directly down-regulating its two important upstream regulators, namely, integrin-linked kinase and PIK3R1. Notably, overexpressing miR-542-3p decreased AKT1 phosphorylation and directly and indirectly repressed nuclear translocation and transactivation activity of β-catenin to exert its anti-invasive effect. Furthermore, the miR-542-3p expression level negatively correlated with AKT activity as well as levels of integrin-linked kinase and PIK3R1 in human astrocytoma specimens. These findings suggest that miR-542-3p acts as a negative regulator in astrocytoma progression and that miR-542-3p down-regulation contributes to aberrant activation of AKT signaling, leaving open the possibility that miR-542-3p may be a potential therapeutic target for high grade astrocytoma. PMID:26286747

  10. Ammonium-induced calcium mobilization in 1321N1 astrocytoma cells

    SciTech Connect

    Hillmann, Petra; Koese, Meryem; Soehl, Kristina; Mueller, Christa E.

    2008-02-15

    High blood levels of ammonium/ammonia (NH{sub 4}{sup +}/NH{sub 3}) are associated with severe neurotoxicity as observed in hepatic encephalopathy (HE). Astrocytes are the main targets of ammonium toxicity, while neuronal cells are less vulnerable. In the present study, an astrocytoma cell line 1321N1 and a neuroblastoma glioma hybrid cell line NG108-15 were used as model systems for astrocytes and neuronal cells, respectively. Ammonium salts evoked a transient increase in intracellular calcium concentrations ([Ca{sup 2+}]{sub i}) in astrocytoma (EC{sub 50} = 6.38 mM), but not in NG108-15 cells. The ammonium-induced increase in [Ca{sup 2+}]{sub i} was due to an intracellular effect of NH{sub 4}{sup +}/NH{sub 3} and was independent of extracellular calcium. Acetate completely inhibited the ammonium effect. Ammonium potently reduced calcium signaling by G{sub q} protein-coupled receptors (H{sub 1} and M3) expressed on the cells. Ammonium (5 mM) also significantly inhibited the proliferation of 1321N1 astrocytoma cells. While mRNA for the mammalian ammonium transporters RhBG and RhCG could not be detected in 1321N1 astrocytoma cells, both transporters were expressed in NG108-15 cells. RhBG and RhBC in brain may promote the excretion of NH{sub 3}/NH{sub 4}{sup +} from neuronal cells. Cellular uptake of NH{sub 4}{sup +}/NH{sub 3} was mainly by passive diffusion of NH{sub 3}. Human 1321N1 astrocytoma cells appear to be an excellent, easily accessible human model for studying HE, which can substitute animal studies, while NG108-15 cells may be useful for investigating the role of the recently discovered Rhesus family type ammonium transporters in neuronal cells. Our findings may contribute to the understanding of pathologic ammonium effects in different brain cells, and to the treatment of hyperammonemia.

  11. Inhibition of MEK Confers Hypersensitivity to X-radiation in the context of BRAF mutation in a Model of Childhood Astrocytoma

    PubMed Central

    Studebaker, Adam; Bondra, Kathryn; Seum, Star; Shen, Changxian; Phelps, Doris A.; Chronowski, Christopher; Leasure, Justin; Smith, Paul D.; Kurmasheva, Raushan T.; Mo, Xiaokui; Fouladi, Maryam; Houghton, Peter J.

    2015-01-01

    Purpose Curative therapy for childhood glioma presents challenges when complete resection is not possible. Patients with recurrent low-grade tumors or anaplastic astrocytoma may receive radiation treatment, however, the long-term sequellae from radiation treatment can be severe. As many childhood gliomas are associated with activation of BRAF, we have explored the combination of ionizing radiation with MEK inhibition in a model of BRAF-mutant anaplastic astrocytoma. Experimental Design The regulation of TORC1 signaling by BRAF was examined in BT-40 (BRAF mutant) and BT-35 (BRAF wild type) xenografts, in a cell line derived from the BT-40 xenograft and two adult BRAF mutant glioblastoma cell lines. The effect of MEK inhibition (selumetinib), XRT (total dose10 Gy as 2 Gy daily fractions), or the combination of selumetinib and XRT was evaluated in subcutaneous BT-40 xenografts. Results Inhibition of MEK signaling by selumetinib, suppressed TORC1 signaling only in the context of the BRAF-mutant both in vitro and in vivo. Inhibition of MEK signaling in BT-40 cells or in xenografts lead to a complete suppression of FANCD2 and conferred hypersensitivity to XRT in BT-40 xenografts without increasing local skin toxicity. Conclusions Selumetinib suppressed TORC1 signaling in the context of BRAF mutation. Selumetinib caused a rapid downregulation of FANCD2 and markedly potentiated the effect of XRT. These data suggest the possibility of potentiating the effect of XRT selectively in tumor cells by MEK inhibition in the context of mutant BRAF or maintaining tumor control at lower doses of XRT that would decrease long-term sequelae. PMID:25981859

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

    PubMed

    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 < 0.001). 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.

  13. Nuclear phosphorylated Y142 β-catenin accumulates in astrocytomas and glioblastomas and regulates cell invasion

    PubMed Central

    Náger, Mireia; Santacana, Maria; Bhardwaj, Deepshikha; Valls, Joan; Ferrer, Isidre; Nogués, Pere; Cantí, Carles; Herreros, Judit

    2015-01-01

    Abstract Glioblastoma multiforme (GBM) is a fast growing brain tumor characterized by extensive infiltration into the surrounding tissue and one of the most aggressive cancers. GBM is the most common glioma (originating from glial-derived cells) that either evolves from a low grade astrocytoma or appears de novo. Wnt/β-catenin and Hepatocyte Growth Factor (HGF)/c-Met signaling are hyperactive in human gliomas, where they regulate cell proliferation, migration and stem cell behavior. We previously demonstrated that β-catenin is phosphorylated at Y142 by recombinant c-Met kinase and downstream of HGF signaling in neurons. Here we studied phosphoY142 (PY142) β-catenin and dephospho S/T β-catenin (a classical Wnt transducer) in glioma biopsies, GBM cell lines and biopsy-derived glioma cell cultures. We found that PY142 β-catenin mainly localizes in the nucleus and signals through transcriptional activation in GBM cells. Tissue microarray analysis confirmed strong nuclear PY142 β-catenin immunostaining in astrocytoma and GBM biopsies. By contrast, active β-catenin showed nuclear localization only in GBM samples. Western blot analysis of tumor biopsies further indicated that PY142 and active β-catenin accumulate independently, correlating with the expression of Snail/Slug (an epithelial-mesenchymal transition marker) and Cyclin-D1 (a regulator of cell cycle progression), respectively, in high grade astrocytomas and GBMs. Moreover, GBM cells stimulated with HGF showed increasing levels of PY142 β-catenin and Snail/Slug. Importantly, the expression of mutant Y142F β-catenin decreased cell detachment and invasion induced by HGF in GBM cell lines and biopsy-derived cell cultures. Our results identify PY142 β-catenin as a nuclear β-catenin signaling form that downregulates adhesion and promotes GBM cell invasion. PMID:26654598

  14. miRNA regulation of Sirtuin-1 expression in human astrocytoma

    PubMed Central

    Romeo, Sara Giovanna; Conti, Alfredo; Polito, Francesca; Tomasello, Chiara; Barresi, Valeria; La Torre, Domenico La; Cucinotta, Maria; Angileri, Flavio Filippo; Bartolotta, Marcello; Di Giorgio, Rosa Maria; Aguennouz, M'Hammed

    2016-01-01

    Sirtuins are a family of 7 histone deacetylases largely involved in the regulation of cell proliferation, survival and death. The role of sirtuins in tumorigenesis and cancer progression has been previously studied in certain cancer types. Few studies have investigated sirtuin expression in gliomas, with controversial results. The aim of the present study was to investigate the expression of sirtuin-1 (Sirt-1) in diffuse astrocytoma [low grade astrocytoma (LGA)], anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM) and in primary glioma cell lines: PLGAC (primary LGA cells); PAAC (primary AA cells); and PGBMC (primary GBM cells). Tumor samples were obtained from patients who underwent craniotomy for microsurgical tumor resection at the Neurosurgery Unit of the University of Messina between 2011 and 2014. Sirt-1 expression was qualitatively analyzed in 30 human glial tumor samples and 5 non-neoplastic brain tissue (NBT) specimens using immunohistochemistry and western blotting techniques. Sirt-1 expression was quantitatively analyzed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). In addition, Sirt-1 expression in primary cell lines was investigated by immunoblotting and RT-qPCR. Sirt-1 expression was downregulated in gliomas compared to NBTs. Sirt-1 levels also varied among different tumor grades, with more evident downregulation in high-grade (P<0.001) than low-grade tumors (P<0.01). These data were confirmed in cell lines, with the exception of upregulation of protein level in the highest malignancy grade cell lines. The present results suggest a role for miRNA-34a, miRNA-132 and miRNA-217 in the epigenetic control of Sirt-1 during gliomagenesis and progression, and demonstrate the different implications of Sirt-1 in human tissues and cell lines. Furthermore, the present results reveal that Sirt-1 may be an intrinsic regulator of tumor progression and the regulation of Sirt-1 involves complex molecular pathways. However, the

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

    PubMed

    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.

  16. Dual effects of mastoparan on intracellular free Ca2+ concentrations in human astrocytoma cells.

    PubMed Central

    Nakahata, N.; Ishimoto, H.; Mizuno, K.; Ohizumi, Y.; Nakanishi, H.

    1994-01-01

    1. The effect of mastoparan, a wasp venom toxin, on intracellular free Ca2+ concentration ([Ca2+]i) was examined in human astrocytoma cells. Mastoparan inhibited [Ca2+]i induced by carbachol (100 microM) in a concentration-dependent manner in the absence of extracellular Ca2+, consistent with our previous results showing that mastoparan inhibits phosphoinositide hydrolysis in human astrocytoma cells. 2. In contrast, mastoparan itself increased [Ca2+]i and augmented carbachol-induced increase in the [Ca2+]i in the presence of extracellular Ca2+, suggesting that mastoparan elicited Ca2+ influx from the extracellular medium. The increase appeared to be maximum at extracellular Ca2+ concentrations of 0.1-0.2 mM. The higher concentrations of extracellular Ca2+ depressed the influx. 3. Pertussis toxin did not affect mastoparan-induced inhibition of [Ca2+]i in the absence of extracellular Ca2+, consistent with the previous results that pertussis toxin did not affect mastoparan-induced inhibition of phosphoinositide hydrolysis. 4. Pertussis toxin augmented mastoparan-induced increase in [Ca2+]i in the presence of extracellular Ca2+, suggesting that pertussis toxin substrate(s) seems to be inhibitory for Ca2+ influx induced by mastoparan. 5. Verapamil, nifedipine and diltiazem (each 10 microM), L-type Ca2+ antagonists, did not affect mastoparan-induced Ca2+ influx. However, verapamil (10 microM) slightly inhibited the increase in [Ca2+]i induced by carbachol in the presence of mastoparan. 6. The results obtained in the present study indicate that mastoparan has two opposite effects on [Ca2+]i in human astrocytoma cells and possibly has at least two sites of action. PMID:8032654

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

    PubMed

    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.

  18. Astrocytoma in an African hedgehog (Atelerix albiventris) suspected wobbly hedgehog syndrome.

    PubMed

    Nakata, Makoto; Miwa, Yasutsugu; Itou, Takuya; Uchida, Kazuyuki; Nakayama, Hiroyuki; Sakai, Takeo

    2011-10-01

    A 28-month-old African hedgehog was referred to our hospital with progressive tetraparesis. On the first presentation, the hedgehog was suspected as having wobbly hedgehog syndrome (WHS) and the animal was treated with medication and rehabilitation. The animal died 22 days after onset. Pathological examination revealed that the animal was involved in astrocytoma between the medulla oblongata and the spinal cord (C1). This report indicates that a primary central nervous system tumor should be considered as one of the differential diagnoses for hedgehogs presenting with progressive paresis, together with WHS.

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

    PubMed Central

    Vaquero, Encarna; Gómez, Carlos M; Quintero, Eliana A; González-Rosa, Javier J; Márquez, Javier

    2008-01-01

    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. Conclusion Results

  20. Ollier disease with anaplastic astrocytoma: A review of the literature and a unique case

    PubMed Central

    Gajavelli, Srikanth; Nakhla, Jonathan; Nasser, Rani; Yassari, Reza; Weidenheim, Karen M.; Graber, Jerome

    2016-01-01

    Background: Ollier disease is a rare, nonfamilial disorder that primary affects the long bones and cartilage of joints with multiple enchondromas. It is associated with a higher risk of central nervous system (CNS) malignancies; although the incidence is unknown. Case Description: Here, we present the case of a 55-year-old woman who developed an anaplastic astrocytoma with a known diagnosis of Ollier disease with a survival time of over 3 years. Conclusion: This report draws attention to the rarity of this disease and the paucity of information regarding CNS involvement in Ollier disease, as well as reviews the current literature. PMID:27656320

  1. Gelastic seizures and low-grade hypothalamic astrocytoma: a case report.

    PubMed

    Coppola, Giangennaro; Spagnoli, Diego; Sciscio, Nicola; Russo, Francesco; Villani, Roberto Matteo

    2002-04-01

    The typical, well recognized childhood epilepsy syndrome caused by hypothalamic hamartoma is characterized by early-onset, stereotyped attacks of uncontrollable laughter, frequent refractory seizures with progressive cognitive deterioration and severe behavioral problems. Here, we report a 17-year-old patient with gelastic phenomenon started in the neonatal period, later on associated with drug resistant polymorphic seizures, intellectual deficit and behavioral disorders, who improved by partial resection of an expected hypothalamic hamartoma that, in turn, resulted to be a hypothalamic low-grade astrocytoma.

  2. New world primates as a model of viral-induced astrocytomas.

    PubMed

    Houff, S A; London, W T; Zu Rhein, G M; Padgett, B L; Walker, D L; Sever, J L

    1983-01-01

    Owl and squirrel monkeys are susceptible to the oncogenic effects of JCV. These species of New World monkeys can be safely inoculated intracerebrally. Care must be taken with owl monkeys since they have an inherited clotting abnormality. Incubation times for the development of tumors range from 14 to 30 months. Anorexia was the first clinical sign of tumor development. The clinical course is rapid with death within two to three days. This model provides a means for studying diagnostic, virological, immunological and therapeutic techniques which are applicable to human patients with astrocytomas.

  3. Unusual Synchronous Presentation of Maxillary Sinus Fibrosarcoma and Gemistocytic Astrocytoma with a Complication Called Leukocytoclastic Vasculitis: A Case Report

    PubMed Central

    Cadir, Bilge; Karahan, Nermin; Nasir, Serdar; Aydin, M. Asim; Turkaslan, S. Suha

    2009-01-01

    Fibrosarcoma of the paranasal sinuses is extremely rare pathology and there is limited report in the literature. We report synchronous presentation of maxillary sinus fibrosarcoma and gemistocytic astrocytoma which is, to our knowledge, unique in the literature. Both tumors metastases to other organ rarely and the metastatic spread of gemistocytic astrocytoma to fibrosarcoma or vice versa have also not been reported in the literature yet. This report discusses the clinical course of the disease, outcome of the treatment approach and survival as well as an unusual occurrence of leukocytoclastic vasculitis during the course of radiotherapy in such unusual presentation. PMID:19756200

  4. Pleiotrophin promotes vascular abnormalization in gliomas and correlates with poor survival in patients with astrocytomas.

    PubMed

    Zhang, Lei; Kundu, Soumi; Feenstra, Tjerk; Li, Xiujuan; Jin, Chuan; Laaniste, Liisi; El Hassan, Tamador Elsir Abu; Ohlin, K Elisabet; Yu, Di; Olofsson, Tommie; Olsson, Anna-Karin; Pontén, Fredrik; Magnusson, Peetra U; Nilsson, Karin Forsberg; Essand, Magnus; Smits, Anja; Dieterich, Lothar C; Dimberg, Anna

    2015-12-08

    Glioblastomas are aggressive astrocytomas characterized by endothelial cell proliferation and abnormal vasculature, which can cause brain edema and increase patient morbidity. We identified the heparin-binding cytokine pleiotrophin as a driver of vascular abnormalization in glioma. Pleiotrophin abundance was greater in high-grade human astrocytomas and correlated with poor survival. Anaplastic lymphoma kinase (ALK), which is a receptor that is activated by pleiotrophin, was present in mural cells associated with abnormal vessels. Orthotopically implanted gliomas formed from GL261 cells that were engineered to produce pleiotrophin showed increased microvessel density and enhanced tumor growth compared with gliomas formed from control GL261 cells. The survival of mice with pleiotrophin-producing gliomas was shorter than that of mice with gliomas that did not produce pleiotrophin. Vessels in pleiotrophin-producing gliomas were poorly perfused and abnormal, a phenotype that was associated with increased deposition of vascular endothelial growth factor (VEGF) in direct proximity to the vasculature. The growth of pleiotrophin-producing GL261 gliomas was inhibited by treatment with the ALK inhibitor crizotinib, the ALK inhibitor ceritinib, or the VEGF receptor inhibitor cediranib, whereas control GL261 tumors did not respond to either inhibitor. Our findings link pleiotrophin abundance in gliomas with survival in humans and mice, and show that pleiotrophin promotes glioma progression through increased VEGF deposition and vascular abnormalization.

  5. An acid phosphatase in the plasma membranes of human astrocytoma showing marked specificity toward phosphotyrosine protein.

    PubMed

    Leis, J F; Kaplan, N O

    1982-11-01

    The plasma membrane from the human tumor astrocytoma contains an active acid phosphatase activity based on hydrolysis of p-nitrophenyl phosphate. Other acid phosphatase substrates--beta-glycerophosphate, O-phosphorylcholine, and 5'-AMP--are not hydrolyzed significantly. The phosphatase activity is tartrate insensitive and is stimulated by Triton X-100 and EDTA. Of the three known phosphoamino acids, only free O-phosphotyrosine is hydrolyzed by the membrane phosphatase activity. Other acid phosphatases tested from potato, wheat germ, milk, and bovine prostate did not show this degree of specificity. The plasma membrane activity also dephosphorylated phosphotyrosine histone at a much greater rate than did the other acid phosphatases. pH profiles for free O-phosphotyrosine and phosphotyrosine histone showed a shift toward physiological pH, indicating possible physiological significance. Phosphotyrosine histone dephosphorylation activity was nearly 10 times greater than that seen for phosphoserine histone dephosphorylation, and Km values were much lower for phosphotyrosine histone dephosphorylation (0.5 microM vs. 10 microM). Fluoride and zinc significantly inhibited phosphoserine histone dephosphorylation. Vanadate, on the other hand, was a potent inhibitor of phosphotyrosine histone dephosphorylation (50% inhibition at 0.5 microM) but not of phosphoserine histone. ATP stimulated phosphotyrosine histone dephosphorylation (160-250%) but inhibited phosphoserine histone dephosphorylation (95%). These results suggest the existence of a highly specific phosphotyrosine protein phosphatase activity associated with the plasma membrane of human astrocytoma.

  6. Variation in DNA repair gene XRCC3 affects susceptibility to astrocytomas and glioblastomas.

    PubMed

    Custódio, A C; Almeida, L O; Pinto, G R; Santos, M J; Almeida, J R W; Clara, C A; Rey, J A; Casartelli, C

    2012-02-10

    The gene XRCC3 (X-ray cross complementing group 3) has the task of repairing damage that occurs when there is recombination between homologous chromosomes. Repair of recombination between homologous chromosomes plays an important role in maintaining genome integrity, although it is known that double-strand breaks are the main inducers of chromosomal aberrations. Changes in the XRCC3 protein lead to an increase in errors in chromosome segregation due to defects in centrosomes, resulting in aneuploidy and other chromosomal aberrations, such as small increases in telomeres. We examined XRCC3 Thr241Met polymorphism using PCR-RFLP in 80 astrocytoma and glioblastoma samples. The individuals of the control group (N = 100) were selected from the general population of the São Paulo State. Odds ratio and 95%CI were calculated using a logistic regression model. Patients who had the allele Met of the XRCC3 Thr241Met polymorphism had a significantly increased risk of tumor development (odds ratio = 3.13; 95% confidence interval = 1.50-6.50). There were no significant differences in overall survival of patients. We suggest that XRCC3 Thr241Met polymorphism is involved in susceptibility for developing astrocytomas and glioblastomas.

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

    PubMed

    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.

  8. Erlotinib Hydrochloride and Isotretinoin in Treating Patients With Recurrent Malignant Glioma

    ClinicalTrials.gov

    2017-02-20

    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

  9. Effects of dexamethasone and betamethasone on in vitro cultures from human astrocytoma.

    PubMed

    Guner, M; Freshney, R I; Morgan, D; Freshney, M G; Thomas, D G; Graham, D I

    1977-04-01

    Cultures of human astrocytoma have been derived by collagenase digestion and are presumed, from their aneuploid karyotypes, to be predominantly neoplastic. Early passage cultures in proliferative phase have been cloned in the presence of dexamethasone and betamethasone, both commonly used in management of patients with brain tumours. These steroids raise both the cloning efficiency and the proliferative capacity of cells within each clone. Inhibition was detected only in very high steroid concentrations (25-50 microng/ml). Since these concentrations are unlikely to be attained in vivo it is concluded that anticipated physiological levels of these steroids enhance cell survival at low densities in culture. The significance of this in vivo is discussed.

  10. Effects of dexamethasone and betamethasone on in vitro cultures from human astrocytoma.

    PubMed Central

    Guner, M.; Freshney, R. I.; Morgan, D.; Freshney, M. G.; Thomas, D. G.; Graham, D. I.

    1977-01-01

    Cultures of human astrocytoma have been derived by collagenase digestion and are presumed, from their aneuploid karyotypes, to be predominantly neoplastic. Early passage cultures in proliferative phase have been cloned in the presence of dexamethasone and betamethasone, both commonly used in management of patients with brain tumours. These steroids raise both the cloning efficiency and the proliferative capacity of cells within each clone. Inhibition was detected only in very high steroid concentrations (25-50 microng/ml). Since these concentrations are unlikely to be attained in vivo it is concluded that anticipated physiological levels of these steroids enhance cell survival at low densities in culture. The significance of this in vivo is discussed. Images Fig. 1 Fig. 2(a) Fig. 2(b) PMID:869982

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

    PubMed

    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.

  12. Intramedullary pilomyxoid astrocytoma with intracerebral metastasis exhibiting oligoden-droglioma-like features

    PubMed Central

    Eigenbrod, Sabina; Thon, Niklas; Jansen, Nathalie; Janssen, Hendrik; Mielke, Janina; Ruiter, Michael; la Fougère, Christian; Peraud, Aurelia; Egensperger, Rupert; Kretzschmar, Hans

    2012-01-01

    Intramedullary glioma are rare and their biological behaviour can differ from their cerebral counterparts. Pilomyxoid astrocytoma (PMA, WHO grade II), predominantly occur in the hypothalamic/chiasmatic region of infants and children. The few reported cases of pediatric intramedullary PMA displayed a particularly aggressive behavior. Here, we report a diagnostically challenging case of a five year old female patient presenting with intramedullary glioma and local tumor recurrence three years later. Twelve years after the initial manifestation, a second tumor was found intracerebrally. We performed a comprehensive histological, molecular pathological and imaging analysis of the tumors from both localizations. The results revealed a metastasizing PMA with unique histological and genetic features. Our study indicates that PMA comprise a heterogeneous group including aggressive subtypes which may not be compatible with the current classification according to WHO grade II. Furthermore, the case emphasizes the increasing relevance of molecular pathological markers complementing classic histo-logical diagnosis. PMID:22826787

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

    PubMed

    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.

  14. Mastoparan-induced phosphatidylcholine hydrolysis by phospholipase D activation in human astrocytoma cells.

    PubMed Central

    Mizuno, K.; Nakahata, N.; Ohizumi, Y.

    1995-01-01

    1. The effect of mastoparan on phosphatidylcholine hydrolysis was examined in 1321N1 human astrocytoma cells. Mastoparan (3-30 microM) caused an accumulation of diacylglycerol (DG) and phosphatidic acd (PA) accompanied by choline release in a concentration- and time-dependent manner. 2. In the presence of 2% n-butanol, mastoparan (3-100 microM) induced phosphatidylbutanol (PBut) accumulation in a concentration- and time-dependent manner, suggesting that mastoparan activates phospholipase D (PLD). Propranolol (30-300 microM), a phosphatidate phosphohydrolase inhibitor, inhibited DG accumulation induced by mastoparan, supporting this idea. 3. Depletion of extracellular free calcium ion did not alter the effect of mastoparan on PLD activity. 4. A protein kinase C (PKC) inhibitor, calphostin C (1 microM), did not inhibit mastoparan-induce PLD activation but the ability of mastoparan to stimulate phospholipase D activity was decreased in the PKC down regulated cells. 5. PLD activity stimulated by mastoparan was not prevented by pretreatment of the cells with pertussis toxin (PT) or C3 ADP-ribosyltransferase. Furthermore, guanine nucleotides did not affect PLD activity stimulation by mastoparan in membrane preparations. 6. Mastoparan stimulated PLD in several cell lines such as RBL-2H3, RBL-1, HL-60, P388, endothelial cells, as well as 1321N1 human astrocytoma cells. 7. These results suggest that mastoparan induces phosphatidylcholine (PC) hydrolysis by activation of PLD, not by activation of phosphatidylcholine-specific phospholipase C (PC-PLC); mastoparan-induced PLD activation is not mediated by G proteins. PMID:8640350

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

    PubMed

    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.

  16. Diagnostic discrepancies in malignant astrocytoma due to limited surgical resection can be overcome by IDH1 testing

    PubMed Central

    Kim, Betty Y. S.; Jiang, Wen.; Beiko, Jason; Prabhu, Sujit S.; DeMonte, Franco; Gilbert, Mark R.; Sawaya, Raymond; Aldape, Kenneth D.; Cahill, Daniel P.; McCutcheon, Ian E.

    2015-01-01

    Background The accurate grading of malignant astrocytomas has significant prognostic and therapeutic implications. Traditional histopathological grading can be challenging due to regional tumor heterogeneity, especially in scenarios where small amounts of tissue are available for pathologic review. Here, we hypothesized that a critical tumor resection volume is needed for correct grading of astrocytomas by histopathology. For insufficient tissue sampling, IDH1 molecular testing can act as a complementary marker to improve diagnostic accuracy. Methods Volumetric analyses were obtained using preoperative and postoperative MRI images. Histological specimens were gathered from 403 patients with malignant astrocytoma who underwent craniotomy. IDH1 status was assessed by immunohistochemistry and sequencing. Results Patients with >20 cubic centimeters (cc) of the total tumor volume resected on MRI have higher rate of GBM diagnosis compared to <20cc (OR 2.57, 95% CI 1.6-4.06, P<0.0001). The rate of IDH1 status remained constant regardless of the tumor volume resected (OR 0.81, 95% CI 0.48-1.36, P<0.43). The rate of GBM diagnosis is 2-fold greater for individual surgical specimen >10cc than those of lower volume (OR 2.48, 95% CI 1.88-3.28, P<0.0001). Overall survival for AA patients with >20cc tumor resection on MRI is significantly better than those with <20cc tumor resected (P<0.05). No volume-dependent differences were observed in patients with GBM (P<0.4), IDH1 wild type (P<0.1) or IDH1 mutation (P<0.88). Conclusions IDH1 status should be considered when total resection volume is <20cc based on MRI analysis and for surgical specimen < 10cc to complement histopathologic diagnosis of malignant astrocytomas. In these specimens, under-diagnosis of GBM may occur when analysis is restricted to histopathology alone. PMID:24777756

  17. Sequentially Programmed Magnetic Field Therapy in the Management of Recurrent Anaplastic Astrocytoma: A Case Report and Literature Review

    PubMed Central

    Vasishta, V.G.

    2010-01-01

    Background Anaplastic astrocytomas are progressive brain tumors with a tendency to infiltrate the surrounding tissue. Recurrence is very common, with recurrent tumors being extremely refractory to existing therapies. Case Presentation: A 33-year-old woman presented with a history of an unprovoked fall, followed by seizures. An MRI scan revealed a mass in the fronto-temporo-parietal region of the brain, suggesting a primary tumor. She underwent craniotomy and surgical debulking of the tumor. The histology of the tumor tissue revealed an anaplastic astrocytoma. Follow-up MRI scans indicated the presence of a residual, rapidly progressing tumor. A 6-week course of fractionated radiation and concurrent chemotherapy with Temodar® (temozolomide capsules) did not stop tumor progression. Intervention: Due to the failure of conventional therapies in preventing rapid disease progression, the patient volunteered to undergo a 28-day course of Sequentially Programmed Magnetic Field (SPMF) therapy. Results Immediate post-therapy MRI scan showed a cessation of tumor growth, and follow-up imaging at 6, 12, 24 and 36 months revealed a gradual but steady decrease in the size of the tumor. The patient reported an alleviation of clinical symptoms and a subjective improvement in the quality of life at 6, 12, 24 and 36 months following SPMF therapy. Conclusion The remarkable improvement of this patient suggests that SPMF therapy may be a valuable option for anaplastic astrocytoma, especially in recurrent and rapidly progressing tumors. PMID:20740195

  18. Radial expansion rates and tumor growth kinetics predict malignant transformation in contrast-enhancing low-grade diffuse astrocytoma

    PubMed Central

    Hathout, Leith; Pope, Whitney B; Lai, Albert; Nghiemphu, Phioanh L; Cloughesy, Timothy F; Ellingson, Benjamin M

    2015-01-01

    Summary Background Contrast-enhancing low-grade diffuse astrocytomas are an understudied, aggressive subtype at increased risk because of few radiographic indications of malignant transformation. In the current study, we tested whether tumor growth kinetics could identify tumors that undergo malignant transformation to higher grades. Methods Thirty patients with untreated diffuse astrocytomas (WHO II) that underwent tumor progression were enrolled. Contrast-enhancing and T2 hyperintense tumor regions were segmented and the radius of tumor at two time points leading to progression was estimated. Radial expansion rates were used to estimate proliferation and invasion rates using a biomathematical model. Results Radial expansion rates for both contrast-enhancing (p = 0.0040) and T2 hyperintense regions (p = 0.0016) were significantly higher in WHO II–IV tumors compared with nontransformers. Similarly, model estimates showed a significantly higher proliferation (p = 0.0324) and invasion rate (p = 0.0050) in WHO II–IV tumors compared with nontransformers. Conclusion Tumor growth kinetics can identify contrast-enhancing diffuse astrocytomas undergoing malignant transformation. PMID:26095141

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

    PubMed

    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 < .001), whereas CREB-1 messenger 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.

  20. Optic glioma

    MedlinePlus

    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 ...

  1. Rapid increase in cystic volume of an anaplastic astrocytoma misdiagnosed as neurocysticercosis: A case report

    PubMed Central

    Li, Hong-Jiang; Han, Hong-Xiu; Feng, Dong-Fu

    2016-01-01

    Reports describing a rapid increase in the cystic volume of anaplastic astrocytoma (AA) in a short time frame are rare. The present study reports the case of a 68-year-old male who was admitted to the No. 9 People's Hospital, Shanghai Jiaotong University School of Medicine (Shanghai, China), with a small cystic brain lesion and positive immunological testing for cysticercosis. Head magnetic resonance imaging (MRI) showed a cystic lesion, 6 mm in diameter, in the left frontal lobe. Neurocysticercosis was suspected and the patient was treated with a clinical trial of albendazole and steroids. A period of 25 days later, the patient's condition had deteriorated, and MRI revealed a cystic lesion in the left frontal lobe; thereafter, the cystic lesion was removed and a diagnosis of AA was established. The tumor was soft, ivory white and gelatinous due to myxoid degeneration. In this case, tumor-related angiogenesis and microvascular extravasation (blood-brain barrier disruption) may have been the main cause of the rapid increase in the cystic volume in such a short time frame. The similarity of the glioma and cysticercus antigens may have been the cause of the positive reactions in the cystic fluid. The present study reports the rare occurrence of a rapid increase of cystic volume and potential diagnostic difficulties. PMID:27698865

  2. Regulation of muscarinic acetylcholine receptors in the 1321N1 human astrocytoma cell line

    SciTech Connect

    Hoover, R.K.

    1989-01-01

    The binding of muscarinic agonists, partial agonists and antagonists to muscarinic receptors of 1321N1 human astrocytoma cells was studied. Binding was studied in both intact cells and cell lysates. Partial agonists and antagonists exhibited similar apparent affinities in intact cell competition binding assays with either the lipophilic radioligand ({sup 3}H)QNB or the hydrophilic radioligand ({sup 3}H)NMS. In contrast, full agonists exhibited markedly lower apparent affinities in intact cells with ({sup 3}H)QNB than with ({sup 3}H)NMS. Treatment of cells with antimycin A to deplete intracellular ATP prevented agonist-induced internalization of muscarinic receptors as assessed by sucrose density gradient assays of receptor subcellular distribution. In ATP-depleted cells, the apparent affinities of full agonists vs ({sup 3}H)QNB were markedly higher. The apparent affinities of partial agonists and of antagonists were unaffected by ATP depletion. In other studies, the effects of the protein kinase C activator phorbol 12-myristate, 13-acetate (PMA) on muscarinic receptor downregulation and internalization in 1321N1 cells were determined. PMA alone did not induce muscarinic receptor downregulation but instead decreased both the rate and final extent of downregulation induced by the agonist carbachol. The specificity of other protein kinase C activators for inhibiting carbachol-induced downregulation indicated involvement of protein kinase C. Furthermore, the protein kinase C inhibitor staurosporine prevented the inhibitory effect of PMA on downregulation. However, staurosporine did not inhibit agonist-induced downregulation.

  3. Recurrent somatic mutations in ACVR1 in pediatric midline high-grade astrocytoma.

    PubMed

    Fontebasso, Adam M; Papillon-Cavanagh, Simon; Schwartzentruber, Jeremy; Nikbakht, Hamid; Gerges, Noha; Fiset, Pierre-Olivier; Bechet, Denise; Faury, Damien; De Jay, Nicolas; Ramkissoon, Lori A; Corcoran, Aoife; Jones, David T W; Sturm, Dominik; Johann, Pascal; Tomita, Tadanori; Goldman, Stewart; Nagib, Mahmoud; Bendel, Anne; Goumnerova, Liliana; Bowers, Daniel C; Leonard, Jeffrey R; Rubin, Joshua B; Alden, Tord; Browd, Samuel; Geyer, J Russell; Leary, Sarah; Jallo, George; Cohen, Kenneth; Gupta, Nalin; Prados, Michael D; Carret, Anne-Sophie; Ellezam, Benjamin; Crevier, Louis; Klekner, Almos; Bognar, Laszlo; Hauser, Peter; Garami, Miklos; Myseros, John; Dong, Zhifeng; Siegel, Peter M; Malkin, Hayley; Ligon, Azra H; Albrecht, Steffen; Pfister, Stefan M; Ligon, Keith L; Majewski, Jacek; Jabado, Nada; Kieran, Mark W

    2014-05-01

    Pediatric midline high-grade astrocytomas (mHGAs) are incurable with few treatment targets identified. Most tumors harbor mutations encoding p.Lys27Met in histone H3 variants. In 40 treatment-naive mHGAs, 39 analyzed by whole-exome sequencing, we find additional somatic mutations specific to tumor location. Gain-of-function mutations in ACVR1 occur in tumors of the pons in conjunction with histone H3.1 p.Lys27Met substitution, whereas FGFR1 mutations or fusions occur in thalamic tumors associated with histone H3.3 p.Lys27Met substitution. Hyperactivation of the bone morphogenetic protein (BMP)-ACVR1 developmental pathway in mHGAs harboring ACVR1 mutations led to increased levels of phosphorylated SMAD1, SMAD5 and SMAD8 and upregulation of BMP downstream early-response genes in tumor cells. Global DNA methylation profiles were significantly associated with the p.Lys27Met alteration, regardless of the mutant histone H3 variant and irrespective of tumor location, supporting the role of this substitution in driving the epigenetic phenotype. This work considerably expands the number of potential treatment targets and further justifies pretreatment biopsy in pediatric mHGA as a means to orient therapeutic efforts in this disease.

  4. Assay of anticancer drugs in tissue culture: cell cultures of biopsies from human astrocytoma.

    PubMed

    Morgan, D; Freshney, R I; Darling, J L; Thomas, D G; Celik, F

    1983-02-01

    A method has been developed for measuring the drug sensitivity of human gliomas in short-term culture, using scintillation counting or autofluorography. Cell cultures prepared from malignant astrocytomas were treated with anticancer drugs whilst in exponential growth in microtitration plates. After drug treatment and a recovery period, residual viability was measured by [3H] leucine incorporation followed by scintillation counting or by [35S] methionine incorporation and autofluorography in situ. In 5 glioma cell lines tested against 6 drugs, the microtitration method correlated well with monolayer cloning. Although replicate samples of the same tumour showed little variation in chemosensitivity, there was marked variation between the chemosensitivities of cultures derived from the tumours of different patients. However, as variability between replicates was apparent during drug exposure or shortly after, it is important to allow the assay to run as long as possible after drug removal. It is hoped that this assay may provide the basis of a method for the prediction of in vivo chemosensitivity or the screening of potential chemotherapeutic drugs.

  5. Assay of anticancer drugs in tissue culture: cell cultures of biopsies from human astrocytoma.

    PubMed Central

    Morgan, D.; Freshney, R. I.; Darling, J. L.; Thomas, D. G.; Celik, F.

    1983-01-01

    A method has been developed for measuring the drug sensitivity of human gliomas in short-term culture, using scintillation counting or autofluorography. Cell cultures prepared from malignant astrocytomas were treated with anticancer drugs whilst in exponential growth in microtitration plates. After drug treatment and a recovery period, residual viability was measured by [3H] leucine incorporation followed by scintillation counting or by [35S] methionine incorporation and autofluorography in situ. In 5 glioma cell lines tested against 6 drugs, the microtitration method correlated well with monolayer cloning. Although replicate samples of the same tumour showed little variation in chemosensitivity, there was marked variation between the chemosensitivities of cultures derived from the tumours of different patients. However, as variability between replicates was apparent during drug exposure or shortly after, it is important to allow the assay to run as long as possible after drug removal. It is hoped that this assay may provide the basis of a method for the prediction of in vivo chemosensitivity or the screening of potential chemotherapeutic drugs. PMID:6297528

  6. H/sub 1/-histamine receptors regulate phosphoinositide hydrolysis in human astrocytoma cells

    SciTech Connect

    Nakahata, N.; Harden, T.K.

    1986-03-05

    Activation of H/sub 1/-histamine receptors on 1321N1 human astrocytoma cells resulted in a rapid formation of the inositol phosphates (InsP), IP/sub 3/, IP/sub 2/, and IP/sub 1/. Histamine-induced mobilization of Ca/sup + +/ and stimulated of a Ca/sup + +/ calmodulin-regulated phosphodiesterase occurred concurrently with histamine-stimulated InsP formation. The K/sub 0.5/ values for histamine for activation of phosphodiesterase, mobilization of Ca/sup + +/, and stimulation of InsP formation were 3,4, and 10 ..mu..M, respectively. The K/sub i/ for histamine determined in competition binding experiments with the H/sub 1/-receptor antagonist, /sup 3/H-mepyramine, was 11 ..mu..M. As with muscarinic receptor-mediated effects in these cells, inactivation of G/sub i/ with pertussis toxin had no effect on H/sub 1/-receptor mediated responses. Both histamine and muscarinic receptor stimulation resulted in the formation of Ins 1,4,5P/sub 3/ and Ins 1,3,4P/sub 3/. In contrast to muscarinic receptor stimulation, which results in a linear accumulation of InsP for greater than 30 min, histamine-stimulated formation of InsP rapidly desensitized.

  7. Everolimus: in patients with subependymal giant cell astrocytoma associated with tuberous sclerosis complex.

    PubMed

    Curran, Monique P

    2012-02-01

    Everolimus is an orally administered inhibitor of the mammalian target of rapamycin (mTOR). Everolimus (starting dosage 3.0 mg/m(2)) was associated with a significant reduction in the volume of the largest subependymal giant cell astrocytoma (SEGA) in 28 patients aged ≥3 years with tuberous sclerosis complex (TSC) in a phase II trial (C2485). At 6 months, 32% of patients treated with everolimus had a ≥50% reduction in the volume of their largest SEGA lesion (assessed via an independent central radiology review); 75% had a ≥30% reduction. No patients developed new lesions. During the extension phase of this trial (median duration 34 months), the reduction in SEGA volume was maintained, with no everolimus recipient requiring surgery or other therapy for SEGA or hydrocephalus. In a phase III trial (EXIST-1) in 117 patients with SEGA associated with TSC, 35% of everolimus recipients (starting dosage 4.5 mg/m(2)) versus none of the placebo recipients (p < 0.0001) had an overall response (a reduction in the sum of all target SEGA volumes of ≥50% relative to baseline, nonworsening of non-target SEGA lesions, no new SEGA lesions, and no new/worsening hydrocephalus). Everolimus was generally well tolerated in patients with SEGA associated with TSC; most drug-related adverse reactions were mild to moderate in severity.

  8. Purine and pyrimidine nucleosides preserve human astrocytoma cell adenylate energy charge under ischemic conditions.

    PubMed

    Balestri, Francesco; Giannecchini, Michela; Sgarrella, Francesco; Carta, Maria Caterina; Tozzi, Maria Grazia; Camici, Marcella

    2007-02-01

    The brain depends on both glycolysis and mitochondrial oxidative phosphorylation for maintenance of ATP pools. Astrocytes play an integral role in brain functions providing trophic supports and energy substrates for neurons. In this paper, we report that human astrocytoma cells (ADF) undergoing ischemic conditions may use both purine and pyrimidine nucleosides as energy source to slow down cellular damage. The cells are subjected to metabolic stress conditions by exclusion of glucose and incubation with oligomycin (an inhibitor of oxidative phosphorylation). This treatment brings about a depletion of the ATP pool, with a concomitant increase in the AMP levels, which results in a significant decrease of the adenylate energy charge. The presence of purine nucleosides in the culture medium preserves the adenylate energy charge, and improves cell viability. Besides purine nucleosides, also pyrimidine nucleosides, such as uridine and, to a lesser extent, cytidine, are able to preserve the ATP pool. The determination of lactate in the incubation medium indicates that nucleosides can preserve the ATP pool through anaerobic glycolysis, thus pointing to a relevant role of the phosphorolytic cleavage of the N-glycosidic bond of nucleosides which generates, without energy expense, the phosphorylated pentose, which through the pentose phosphate pathway and glycolysis can be converted to energetic intermediates also in the absence of oxygen. In fact, ADF cells possess both purine nucleoside phosphorylase and uridine phosphorylase activities.

  9. Stereotactic interstitial brachytherapy of malignant astrocytomas with remarks on postimplantation computed tomographic appearance

    SciTech Connect

    Willis, B.K.; Heilbrun, M.P.; Sapozink, M.D.; McDonald, P.R.

    1988-09-01

    Seventeen patients were treated with stereotactically implanted high activity iodine-125 seeds, 12 patients for recurrent malignant astrocytomas (Protocol I) and 5 patients for newly diagnosed glioblastomas (Protocol II). Total radiation dosage to the recurrent tumors in Protocol I, including prior external beam irradiation, averaged 13,500 cGy. In the follow-up period of 6 to 50 months, the survival rate was 93% at 6 months, 60% at 12 months, 50% at 18 months, and 38% at 24 months after implantation. In Protocol II, brachytherapy was used as an interstitial radiation boost to the conventional treatment of newly diagnosed glioblastomas. External beam therapy and interstitial brachytherapy provided 11,000 cGy to these tumors. In the follow-up period of 15 to 27 months, there was a 100% survival at 12 months, 75% at 18 months, and 25% at 24 months after implantation. Eight of our 17 patients required reoperation for persistent or recurrent mass lesions at 6 to 15 months postimplantation; 7 were found to harbor masses of radionecrosis containing nests of anaplastic astrocytes; 1 had frank tumor recurrence. Median survival in this group of patients requiring reoperation was 18.7 months postimplantation. In a review of postimplantation computed tomographic scans, significant mass effect and crossover of hypodensity or enhancement into the corpus callosum or opposite hemisphere were found to have prognostic significance; persistent areas of contrast enhancement and excessive peritumoral hypodensity did not.

  10. Infective capacity of Cryptococcus neoformans and Cryptococcus gattii in a human astrocytoma cell line.

    PubMed

    Olave, M C; Vargas-Zambrano, J C; Celis, A M; Castañeda, E; González, J M

    2017-03-24

    Pathogenesis of cryptococcosis in the central nervous system (CNS) is a topic of ongoing research, including the mechanisms by which this fungus invades and infects the brain. Astrocytes, the most common CNS cells, play a fundamental role in the local immune response. Astrocytes might participate in cryptococcosis either as a host or by responding to fungal antigens. To determine the infectivity of Cryptococcus neoformans var. grubii and Cryptococcus gattii in a human astrocytoma cell line and the induction of major histocompatibility complex (MHC) molecules. A glioblastoma cell line was infected with C. neoformans var. grubii and C. gattii blastoconidia labelled with FUN-1 fluorescent stain. The percentage of infection and expression of HLA class I and II molecules were determined by flow cytometry. The interactions between the fungi and cells were observed by fluorescence microscopy. There was no difference between C. neoformans var. grubii and C. gattii in the percentage infection, but C. neoformans var. grubii induced higher expression of HLA class II than C. gattii. More blastoconidia were recovered from C. neoformans-infected cells than from C. gattii infected cells. Cryptococcus neoformans var. grubii may have different virulence mechanisms that allow its survival in human glia-derived cells.

  11. Recurrent somatic mutations in ACVR1 in pediatric midline high-grade astrocytoma

    PubMed Central

    Fontebasso, Adam M.; Papillon-Cavanagh, Simon; Schwartzentruber, Jeremy; Nikbakht, Hamid; Gerges, Noha; Fiset, Pierre-Olivier; Bechet, Denise; Faury, Damien; De Jay, Nicolas; Ramkissoon, Lori; Corcoran, Aoife; Jones, David T W; Sturm, Dominik; Johann, Pascal; Tomita, Tadanori; Goldman, Stewart; Nagib, Mahmoud; Bendel, Anne; Goumnerova, Liliana; Bowers, Daniel C.; Leonard, Jeffrey R.; Rubin, Joshua B.; Alden, Tord; Browd, Samuel; Geyer, J. Russell; Leary, Sarah; Jallo, George; Cohen, Kenneth; Gupta, Nalin; Prados, Michael D.; Carret, Anne-Sophie; Ellezam, Benjamin; Crevier, Louis; Klekner, Almos; Bognar, Laszlo; Hauser, Peter; Garami, Miklos; Myseros, John; Dong, Zhifeng; Siegel, Peter M.; Malkin, Hayley; Ligon, Azra; Albrecht, Steffen; Pfister, Stefan M.; Ligon, Keith L.; Majewski, Jacek; Jabado, Nada; Kieran, Mark W

    2014-01-01

    Midline pediatric high-grade astrocytomas (pHGAs) are incurable with few treatment targets identified. Most tumors harbor K27M mutations on histone 3 variants. In 40 treatment-naïve midline pHGAs, 39 analyzed by whole-exome sequencing, we find additional somatic mutations specific to tumor location. Gain-of-function mutations in ACVR1 occur in tumors of the pons in conjunction with H3.1 K27M, while FGFR1 mutations/fusions occur in thalamic tumors associated with H3.3 K27M. Hyper-activation of the bone morphogenetic protein (BMP)/ACVR1 developmental pathway in pHGAs harbouring ACVR1 mutations led to increased phospho-SMAD1/5/8 expression and up-regulation of BMP downstream early response genes in tumour cells. Global DNA methylation profiles were significantly associated with the K27M mutation regardless of the mutant H3 variant and irrespective of tumor location, supporting its role in driving the epigenetic phenotype. This significantly expands the potential treatment targets and further justifies pre-treatment biopsy in pHGA as a means to orient therapeutic efforts in this disease. PMID:24705250

  12. Effect of brefelamide on HGF-induced survival of 1321N1 human astrocytoma cells.

    PubMed

    Honma, Shigeyoshi; Takasaka, Sachina; Ishikawa, Takahiro; Shibuya, Takahiro; Mitazaki, Satoru; Abe, Sumiko; Yoshida, Makoto

    2016-06-01

    Malignant gliomas are characterized by their high level of resistance to chemo- and radiotherapy and new treatment options are urgently required. We previously demonstrated that brefelamide, an aromatic amide isolated from methanol extracts of cellular slime molds Dictyostelium brefeldianum and D. giganteum, had antiproliferative effects on 1321N1 human astrocytoma cells, a model of glioma. In this study, we investigated the mechanisms by which brefelamide inhibited 1321N1 and PC12 rat pheochromocytoma cell proliferation. When cells were cultured in serum-free medium, hepatocyte growth factor (HGF) increased survival of 1321N1 cells but not PC12 cells. HGF receptor, c-MET, was strongly expressed in 1321N1 cells, but not in PC12 cells. Pretreatment of 1321N1 cells with brefelamide inhibited both HGF-induced cell survival and expression of c-MET. Phosphorylation of extracellular signal-regulated kinase (ERK) and AKT was increased by HGF, but these changes were inhibited by brefelamide pretreatment. Moreover, HGF mRNA levels and secretion were reduced by brefelamide. These results suggest that brefelamide reduces survival of 1321N1 cells via multiple effects including suppression of HGF receptor expression and HGF secretion and inhibition of ERK and AKT phosphorylation.

  13. Treatment of pediatric patients and young adults with particle therapy at the Heidelberg Ion Therapy Center (HIT): establishment of workflow and initial clinical data

    PubMed Central

    2012-01-01

    Background To report on establishment of workflow and clinical results of particle therapy at the Heidelberg Ion Therapy Center. Materials and methods We treated 36 pediatric patients (aged 21 or younger) with particle therapy at HIT. Median age was 12 years (range 2-21 years), five patients (14%) were younger than 5 years of age. Indications included pilocytic astrocytoma, parameningeal and orbital rhabdomyosarcoma, skull base and cervical chordoma, osteosarcoma and adenoid-cystic carcinoma (ACC), as well as one patient with an angiofibroma of the nasopharynx. For the treatment of small children, an anesthesia unit at HIT was established in cooperation with the Department of Anesthesiology. Results Treatment concepts depended on tumor type, staging, age of the patient, as well as availability of specific study protocols. In all patients, particle radiotherapy was well tolerated and no interruptions due to toxicity had to be undertaken. During follow-up, only mild toxicites were observed. Only one patient died of tumor progression: Carbon ion radiotherapy was performed as an individual treatment approach in a child with a skull base recurrence of the previously irradiated rhabdomyosarcoma. Besides this patient, tumor recurrence was observed in two additional patients. Conclusion Clinical protocols have been generated to evaluate the real potential of particle therapy, also with respect to carbon ions in distinct pediatric patient populations. The strong cooperation between the pediatric department and the department of radiation oncology enable an interdisciplinary treatment and stream-lined workflow and acceptance of the treatment for the patients and their parents. PMID:23072718

  14. The visuospatial functions in children after cerebellar low-grade astrocytoma surgery: A contribution to the pediatric neuropsychology of the cerebellum.

    PubMed

    Starowicz-Filip, Anna; Chrobak, Adrian Andrzej; Milczarek, Olga; Kwiatkowski, Stanisław

    2015-12-07

    The aim of this study was to specify whether cerebellar lesions cause visuospatial impairments in children. The study sample consisted of 40 children with low-grade cerebellar astrocytoma, who underwent surgical treatment and 40 healthy controls matched with regard to age and sex. Visuospatial abilities were tested using the spatial WISC-R subtests (Block Design and Object Assembly), Rey-Osterrieth Complex Figure, Benton Judgment of Line Orientation Test, PEBL Mental Rotation Task, and Benton Visual Retention Test. To exclude general diffuse intellectual dysfunction, the WISC-R Verbal Intelligence IQ, Performance IQ, and Full-Scale IQ scores were analysed. Post-surgical medical consequences were measured with the International Cooperative Ataxia Rating Scale. Compared to controls, the cerebellar group manifested problems with mental rotation of objects, visuospatial organization, planning, and spatial construction processes which could not be explained by medical complications or general intellectual retardation. The intensity of visuospatial syndrome highly depends on cerebellar lesion side. Patients with left-sided cerebellar lesions display more severe spatial problems than those with right-sided cerebellar lesions. In conclusion, focal cerebellar lesions in children affect their visuospatial ability. The impairments profile is characterized by deficits in complex spatial processes such as visuospatial organization and mental rotation, requiring reconstruction of visual stimuli using the imagination, while elementary sensory analysis and perception as well as spatial processes requiring direct manipulation of objects are relatively better preserved. This pattern is analogous to the one previously observed in adult population and appears to be typical for cerebellar pathology in general, regardless of age.

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

    PubMed Central

    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. PMID:28249041

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

    PubMed

    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.

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

    PubMed

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

    2013-01-01

    Targeting of lysosomes is a novel therapeutic anti-cancer strategy for killing the otherwise apoptosis-resistant cancer cells. Such strategies are urgently needed for treatment of brain tumors, especially the glioblastoma, which is the most frequent and most malignant type. The aim of the present study was to investigate the presence of lysosomes in astrocytic brain tumors focussing also on the therapy resistant tumor stem cells. Expression of the lysosomal marker LAMP-1 (lysosomal-associated membrane protein-1) was investigated by immunohistochemistry in 112 formalin fixed paraffin embedded 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 cells, while the blood vessels were positive in all tumors. The percentage of LAMP-1 positive tumor cells and staining intensities increased with tumor grade but variations in tumors of the same grade were also found. No association was found between LAMP-1 expression and patient overall survival in the individual tumor grades. LAMP-1/GFAP showed pronounced co-expression and LAMP-1/CD133 was co-expressed as well suggesting that tumor cells including the proposed tumor stem cells contain lysosomes. The results suggest that high amounts of lysosomes are present in glioblastomas and in the proposed tumor stem cells. Targeting of lysosomes may be a promising novel therapeutic strategy against this highly malignant neoplasm.

  18. Coexpression of platelet-derived growth factor (PDGF) and PDGF-receptor genes by primary human astrocytomas may contribute to their development and maintenance.

    PubMed Central

    Maxwell, M; Naber, S P; Wolfe, H J; Galanopoulos, T; Hedley-Whyte, E T; Black, P M; Antoniades, H N

    1990-01-01

    The present studies investigated the expression of the two PDGF genes (c-sis/PDGF-2 and PDGF-1) and the PDGF-receptor b gene (PDGF-R) in 34 primary human astrocytomas. Northern blot analysis demonstrated the coexpression of the c-sis/PDGF-2 protooncogene and the PDGF-R gene in all astrocytomas examined. The majority of the tumors also expressed the PDGF-1 gene. There was no correlation between the expression of the two PDGF genes. Nonmalignant human brain tissue expressed the PDGF-R and PDGF-1 genes but not the c-sis/PDGF-2 protooncogene. In situ hybridization of astrocytoma tissue localized the expression of the c-sis and PDGF-R mRNA's in tumor cells. Capillary endothelial cells also expressed c-sis mRNA. In contrast, nonmalignant human brain tissue expressed only PDGF-R mRNA but not c-sis/PDGF-2 mRNA. The coexpression of a potent mitogenic growth factor protooncogene (c-sis) and its receptor gene in astrocytoma tumor cells suggests the presence of an autocrine mechanism that may contribute to the development and maintenance of astrocytomas. The expression of c-sis mRNA in tumor cells but not in nonmalignant brain cells may serve as an additional diagnostic criterion for the detection of astrocytomas in small tissue specimen using in situ hybridization for the detection of c-sis mRNA and/or immunostaining for the recognition of its protein product. Images PMID:2164040

  19. Increased expression of stefin B in the nucleus of T98G astrocytoma cells delays caspase activation

    PubMed Central

    Sun, Tao; Turk, Vito; Turk, Boris; Kopitar-Jerala, Nataša

    2012-01-01

    Stefin B (cystatin B) is an endogenous inhibitor of cysteine proteinases localized in the nucleus and the cytosol. Loss-of-function mutations in the stefin B gene (CSTB) gene were reported in patients with Unverricht-Lundborg disease (EPM1). Our previous results showed that thymocytes isolated from stefin B-deficient mice are more sensitive to apoptosis induced by the protein kinase C (PKC) inhibitor staurosporin (STS) than the wild-type control cells. We have also shown that the increased expression of stefin B in the nucleus of T98G astrocytoma cells delayed cell cycle progression through the S phase. In the present study we examined if the nuclear or cytosolic functions of stefin B are responsible for the accelerated induction of apoptosis observed in the cells from stefin B-deficient mice. We have shown that the overexpression of stefin B in the nucleus, but not in the cytosol of astrocytoma T98G cells, delayed caspase-3 and -7 activation. Pretreatment of cells with the pan-caspase inhibitor z-Val-Ala-Asp(OMe)-fluoromethylketone completely inhibited caspase activation, while treatment with the inhibitor of calpains- and papain-like cathepsins (2S,3S)-trans-epoxysuccinyl-leucylamido-3-methyl-butane ethyl ester did not prevent caspase activation. We concluded that the delay of caspase activation in T98G cells overexpressing stefin B in the nucleus is independent of cathepsin inhibition. PMID:23049497

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

    PubMed Central

    Bailon-Moscoso, Natalia; González-Arévalo, Gabriela; Velásquez-Rojas, Gabriela; Malagon, Omar; Vidari, Giovanni; Zentella-Dehesa, Alejandro; Ratovitski, Edward A.; Ostrosky-Wegman, Patricia

    2015-01-01

    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. PMID:26309132

  1. Prognostic significance of an apoptotic index and apoptosis/proliferation ratio for patients with high-grade astrocytomas.

    PubMed Central

    Kuriyama, Hiroko; Lamborn, Kathleen R.; O'Fallon, Judith R.; Iturria, N.; Sebo, Thomas; Schaefer, Paul L.; Scheithauer, Bernd W.; Buckner, Jan C.; Kuriyama, Nagato; Jenkins, Robert B.; Israel, Mark A.

    2002-01-01

    We evaluated the association of spontaneous apoptosis and an apoptosis/proliferation index with survival to determine the potential of such measures to serve as predictive markers for patients with glioblastoma multiforme (GBM). We examined the extent of spontaneous apoptosis in tumors from newly diagnosed patients, 75 with GBM and 21 with anaplastic astrocytoma, who were entered on treatment protocols of the North Central Cancer Treatment Group. In the group of GBM patients, those with a higher apoptotic index tended to live longer ( P = 0.04; Cox proportional hazards model including performance score, age, and extent of resection in a multivariate model). We found that the apoptotic index values for anaplastic astrocytoma patients tended to be lower than those in the GBM patients, although with small sample sizes, the result was not statistically significant ( P = 0.1). We also examined expression of the Ki-67 cell proliferation antigen immunohistochemically using the MIB-1 monoclonal antibody. Ki-67 expression did not provide additional information regarding the survival of patients with GBM. In this group of GBM patients, those patients with higher apoptotic index/proliferation ratios had a better prognosis than did those with a low ratio ( P < 0.021, same model as above). These findings suggest that both apoptosis and a cell death/cell proliferation ratio are associated with patient survival, and they may be useful for either the clinical evaluation of patients with GBM or the stratification of patients for treatment evaluation. PMID:12084348

  2. A model of a patient-derived IDH1 mutant anaplastic astrocytoma with alternative lengthening of telomeres

    PubMed Central

    Borodovsky, Alexandra; Meeker, Alan K.; Kirkness, Ewen F.; Zhao, Qi; Eberhart, Charles G.; Gallia, Gary L.; Riggins, Gregory J.

    2015-01-01

    Mutations in isocitrate dehydrogenase 1 (IDH1) have been found in the vast majority of low grade and progressive infiltrating gliomas and are characterized by the production of 2-hydroxyglutarate from α-ketoglutarate. Recent investigations of malignant gliomas have identified additional genetic and chromosomal abnormalities which cluster with IDH1 mutations into two distinct subgroups. The astrocytic subgroup was found to have frequent mutations in ATRX, TP53 and displays alternative lengthening of telomeres. The second subgroup with oligodendrocytic morphology has frequent mutations in CIC or FUBP1, and is linked to co-deletion of the 1p/19q arms. These mutations reflect the development of two distinct molecular pathways representing the majority of IDH1 mutant gliomas. Unfortunately, due to the scarcity of endogenously derived IDH1 mutant models, there is a lack of accurate models to study mechanism and develop new therapy. Here we report the generation of an endogenous IDH1 anaplastic astrocytoma in vivo model with concurrent mutations in TP53, CDKN2A and ATRX. The model has a similar phenotype and histopathology as the original patient tumor, expresses the IDH1 (R132H) mutant protein and exhibits an alternative lengthening of telomeres phenotype. The JHH-273 model is characteristic of anaplastic astrocytoma and represents a valuable tool for investigating the pathogenesis of this distinct molecular subset of gliomas and for preclinical testing of compounds targeting IDH1 mutations or alternative lengthening of telomeres. PMID:25471051

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

    PubMed

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

    2016-11-18

    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.

  4. Clinical Factors for Prognosis and Treatment Guidance of Spinal Cord Astrocytoma

    PubMed Central

    Hida, Kazutoshi; Yano, Shunsuke; Aoyama, Takeshi; Koyanagi, Izumi; Sasamori, Toru; Hamauch, Shuji; Houkin, Kiyohiro

    2016-01-01

    Study Design Retrospective study. Purpose To obtain information useful in establishing treatment guidelines by evaluating baseline clinical features and treatment outcomes of patients with spinal cord astrocytoma (SCA). Overview of Literature The optimal management of SCA remains controversial, and there are no standard guidelines. Methods The study included 20 patients with low-grade and 13 with high-grade SCA surgically treated between 1989 and 2014. Patients were classified according to the extent of surgical resection. Survival was assessed using Kaplan–Meier plots and compared between groups by log-rank tests. Neurological status was defined by the modified McCormick scale and compared between groups by Mann–Whitney U tests. Results Surgical resection was performed for 19 of 20 low-grade (95%) and 10 of 13 high-grade (76.9%) SCA patients. Only nine patients (27.3%) underwent gross total resection, all of whom had low-grade SCA. Of all patients, 51.5% showed deteriorated neurological status compared to preoperative baseline. Median overall survival was significantly longer for low-grade SCA than that (91 months, 78% at 5 years vs. 15 months, 31% at 5 years; p=0.007). Low-grade SCA patients benefited from more aggressive resection, whereas high-grade SCA patients did not. Multivariate analysis revealed histology status (hazard ratio [HR], 0.30; 95% confidence interval [CI], 0.09–0.98; p<0.05) and postoperative neurological status (HR, 0.12; CI, 0.02–0.95; p<0.05) as independent predictors of longer overall survival. Adjuvant radiotherapy had no significant impact on survival rate. However, a trend for increased survival was observed with radiation cordotomy (RCT) in high-grade SCA patients. Conclusions Aggressive resection for low-grade and RCT may prolong survival. Preservation of neurological status is an important treatment goal. Given the low incidence of SCA, establishing strong collaborative, interdisciplinary, and multi-institutional study groups

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

    PubMed

    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.

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

    PubMed Central

    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

    2016-01-01

    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. PMID:27626492

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

    PubMed

    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.

  8. Quantitative chromatin pattern description in Feulgen-stained nuclei as a diagnostic tool to characterize the oligodendroglial and astroglial components in mixed oligo-astrocytomas.

    PubMed

    Decaestecker, C; Lopes, B S; Gordower, L; Camby, I; Cras, P; Martin, J J; Kiss, R; VandenBerg, S R; Salmon, I

    1997-04-01

    The oligoastrocytoma, as a mixed glioma, represents a nosologic dilemma with respect to precisely defining the oligodendroglial and astroglial phenotypes that constitute the neoplastic cell lineages of these tumors. In this study, cell image analysis with Feulgen-stained nuclei was used to distinguish between oligodendroglial and astrocytic phenotypes in oligodendrogliomas and astrocytomas and then applied to mixed oligoastrocytomas. Quantitative features with respect to chromatin pattern (30 variables) and DNA ploidy (8 variables) were evaluated on Feulgen-stained nuclei in a series of 71 gliomas using computer-assisted microscopy. These included 32 oligodendrogliomas (OLG group: 24 grade II and 8 grade III tumors according to the WHO classification), 32 astrocytomas (AST group: 13 grade II and 19 grade III tumors), and 7 oligoastrocytomas (OLGAST group). Initially, image analysis with multivariate statistical analyses (Discriminant Analysis) could identify each glial tumor group. Highly significant statistical differences were obtained distinguishing the morphonuclear features of oligodendrogliomas from those of astrocytomas, regardless of their histological grade. When compared with the 7 mixed oligoastrocytomas under study, 5 exhibited DNA ploidy and chromatin pattern characteristics similar to grade II oligodendrogliomas, I to grade III oligodendrogliomas, and I to grade II astrocytomas. Using multifactorial statistical analyses (Discriminant Analysis combined with Principal Component Analysis). It was possible to quantify the proportion of "typical" glial cell phenotypes that compose grade II and III oligodendrogliomas and grade II and III astrocytomas in each mixed glioma. Cytometric image analysis may be an important adjunct to routine histopathology for the reproducible identification of neoplasms containing a mixture of oligodendroglial and astrocytic phenotypes.

  9. Accumulation of wild-type p53 protein in astrocytomas is not mediated by MDM2 gene amplification

    SciTech Connect

    Rubio, M.P.; Louis, D.N. Harvard Medical School, Boston, MA )

    1993-05-01

    The authors have previously described ten cases of astrocytoma (three WHO grade II, four grade III and four grade IV) with seemingly contradictory results on immunohistochemical analysis of the p53 protein and molecular genetic analysis of the p53 gene. Fixed, embedded tissues from these cases were immunohistochemically positive with the PAb 1801 antibody, which supposedly implies the presence of mutant protein. These ten cases, however, did not have mutations in exons 5 through 8 of the p53 gene, the conserved regions in which almost all human mutations have been described. The authors suggested that these cases might either represent overexpression of wild-type p53 protein (since the PAb 1801 antibody reacts with both wild-type and mutant p53 protein) or mutations in less conserved regions of the gene. To investigate these possibilities further, they performed single strand conformational polymorphism analysis and DNA sequencing on p53 exons 4, 9 and 10 in the nine cases with available DNA, since rare mutations have been noted at these loci. None of the cases showed alterations, making it highly unlikely that these tumors harbor mutations in exons of the p53 gene. They also performed immunohistochemistry on frozen sections from seven available tumors, using the mutant-specific antibody PAb 240 in addition to PAb 1801. All tumors continued to show positive staining with PAb 1801, but only one tumor reacted with PAb 240. The results support the hypothesis that the accumulated p53 protein in most cases is wild-type. Because the product of the MDM2 oncogene can bind to wild-type p53 protein, and because MDM2 amplification has recently been demonstrated in human tumors, the authors evaluated MDM2 amplification in the nine astrocytomas with available DNA. Using slot blot analysis with a 96-base pair, PCR-generated probe to the first exon of the MDM2 gene, they were unable to show MDM2 gene amplification in these tumors or in other assayed astrocytomas.

  10. Demonstration of separate phosphotyrosyl- and phosphoseryl- histone phosphatase activities in the plasma membranes of a human astrocytoma.

    PubMed

    Leis, J F; Knowles, A F; Kaplan, N O

    1985-06-01

    A plasma membrane preparation from a human astrocytoma contained p-nitrophenyl phosphate (pNPP), phosphotyrosyl histone, and phosphoseryl histone hydrolysis activities. The pNPPase and phosphotyrosyl histone phosphatase activities were inhibited by vanadate, whereas the phosphoseryl histone phosphatase activity was not; the latter activity was inhibited by pyrophosphate and nucleoside di- and triphosphates. When the membranes were solubilized by Triton X-100 and the solubilized proteins were subjected to column chromatography on DEAE-Sephadex, Sepharose 6B-C1, and wheat germ agglutinin-Sepharose 4B columns, the pNPPase activity from the phosphoseryl histone phosphatase activity. The results from column chromatography also indicated that there may be multiple phosphotyrosyl and phosphoseryl protein phosphatases in the plasma membranes.

  11. Identification and characterization of estrogen receptor-related receptor alpha and gamma in human glioma and astrocytoma cells.

    PubMed

    Gandhari, Mukesh K; Frazier, Chester R; Hartenstein, Julia S; Cloix, Jean-Francois; Bernier, Michel; Wainer, Irving W

    2010-02-05

    The purpose of this study was to examine expression and function of estrogen receptor-related receptors (ERRs) in human glioma and astrocytoma cell lines. These estrogen receptor-negative cell lines expressed ERRalpha and ERRgamma proteins to varying degree in a cell context dependent manner, with U87MG glioma cells expressing both orphan nuclear receptors. Cell proliferation assays were performed in the presence of ERR isoform-specific agonists and antagonists, and the calculated EC(50) and IC(50) values were consistent with previous reported values determined in other types of cancer cell lines. Induction of luciferase expression under the control of ERR isoform-specific promoters was also observed in these cells. These results indicate that ERRalpha and ERRgamma are differentially expressed in these tumor cell lines and likely contribute to agonist-dependent ERR transcriptional activity.

  12. Natural Triterpenic Diols Promote Apoptosis in Astrocytoma Cells through ROS-Mediated Mitochondrial Depolarization and JNK Activation

    PubMed Central

    Martín, Rubén; Ibeas, Elvira; Carvalho-Tavares, Juliana; Hernández, Marita; Ruiz-Gutierrez, Valentina; Nieto, María Luisa

    2009-01-01

    Background Triterpene alcohols and acids are multifunctional compounds widely distributed throughout the plant kingdom that exhibit a variety of beneficial health properties, being synthetic analogs of oleanolic acid under clinical evaluation as anti-tumoral therapeutic agents. However, the antineoplastic activity of two natural occuring triterpenoid alcohols extracted from olive oil, erythrodiol (an intermediate from oleanolic acid), and its isomer, uvaol, has barely been reported, particularly on brain cancer cells. Astrocytomas are among the most common and aggressive type of primary malignant tumors in the neurological system lacking effective treatments, and in this study, we addressed the effect of these two triterpenic diols on the human 1321N1 astrocytoma cell line. Principal Findings Erythrodiol and uvaol effectively affected cell proliferation, as well as cell cycle phases and induced 1321N1 cell death. Both triterpenes successfully modulated the apoptotic response, promoting nuclear condensation and fragmentation. They caused retraction and rounding of cultured cells, which lost adherence from their supports, while F-actin and vimentin filaments disappeared as an organized cytoplasmic network. At molecular level, changes in the expression of surface proteins associated with adhesion or death processes were also observed. Moreover, triterpene exposure resulted in the production of reactive oxygen species (ROS) with loss of mitochondrial transmembrane potential, and correlated with the activation of c-Jun N-terminal kinases (JNK). The presence of catalase reversed the triterpenic diols-induced mitochondrial depolarization, JNK activation, and apoptotic death, indicating the critical role of ROS in the action of these compounds. Conclusions Overall, we provide a significant insight into the anticarcinogenic action of erythrodiol and uvaol that may have a potential in prevention and treatment of brain tumors and other cancers. PMID:19543395

  13. The effect of guggulipid and nimesulide on MPTP-induced mediators of neuroinflammation in rat astrocytoma cells, C6.

    PubMed

    Niranjan, Rituraj; Rajasekar, N; Nath, Chandishwar; Shukla, Rakesh

    2012-12-05

    Oxidative stress plays an important role in the pathophysiology of Parkinson's disease (PD) but its mechanism is still not properly explored. Cyclooxygenase-2 (COX-2) inhibition has also been known a major neuroprotective strategy in the various 1-methyl-4-phenyl 1,2,3,6 tetrahydropyridine (MPTP) induced models of Parkinson's disease (PD) but its role in astrocytes is still not properly understood. The present study demonstrated that, guggulipid and nimesulide (preferentially selective COX-2 inhibitor) treatment of rat astrocytoma cells, C6 for 24 h significantly decreased MPTP (400 μM) induced nitrative and oxidative stress and intracellular calcium ion (Ca(2+)) level. Guggulipid and nimesulide also deactivated MPTP-induced P-p38 MAPK (Phosphorylated p38 mitogen-activated protein kinase) and down regulated expressions of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and CHOP (C/EBP, homologous protein 10). At transcriptional level of inflammatory cytokine genes, guggulipid and nimesulide down regulated MPTP-induced tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) mRNA expressions with up regulations in interleukin-6 (IL-6) and interleukin-1α (IL-1α) mRNA expressions. In addition to this, guggulipid and nimesulide inhibited translocation of nuclear factor kappa-B (NF-κB) from cytosol to nucleus. In conclusion, our findings elucidated the potential antioxidant and anti-neuroinflammatory effect of guggulipid and nimesulide in rat astrocytoma cells C6, which may suggest the use of these drugs in the management of neuroinflammation associated pathophysiology of PD.

  14. p53 protein in low-grade astrocytomas: a study with long-term follow-up.

    PubMed Central

    Iuzzolino, P.; Ghimenton, C.; Nicolato, A.; Giorgiutti, F.; Fina, P.; Doglioni, C.; Barbareschi, M.

    1994-01-01

    The immunohistochemical expression of p53 protein (p53) was examined in 52 patients out of a series of 66 patients with low-grade astrocytomas with long-term follow-up. All patients were also evaluated for several clinical and histological features, among which only preoperative Karnofsky score and the extent of surgery were statistically significant parameters to predict outcome on multivariate analysis. p53 accumulation was seen in 46.1% of patients, with a wide range of percentage of positive cells. Median survival for p53-positive and p53-negative patients was 41 and 37 months respectively. The survival curves of p53-positive and -negative patients were not statistically different. However, the curves showed a trend towards a more aggressive course in p53-positive patients beginning 3-4 years after surgery. Five years after diagnosis the survival estimate with the Kaplan-Meier method was 21.2% for patients with p53-positive tumours and 45.9% for patients with p53-negative tumours. This trend is not due to different distribution of major clinical prognostic factors (age, incomplete resection or Karnofsky status). The trend could be related to the time needed by the p53-positive clone to outgrow the rest of the p53-negative neoplastic cell population. This hypothesis is further supported by the fact that the five recurrences which were surgically removed (one anaplastic astrocytoma and four glioblastomas) derived from p53-positive tumours and were themselves intensely p53 positive. Images Figure 1 PMID:8123492

  15. MiR-181b-5p downregulates NOVA1 to suppress proliferation, migration and invasion and promote apoptosis in astrocytoma.

    PubMed

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

    2014-01-01

    MicroRNAs (miRNAs) are small, short noncoding RNAs that modulate the expression of numerous genes by targeting their mRNA. Numerous abnormal miRNA expression patterns are observed in various human malignancies, and certain miRNAs can act as oncogenes or tumor suppressors. Astrocytoma, the most common neuroepithelial cancer, represents the majority of malignant brain tumors in humans. In our previous studies, we found that the downregulation of miR-181b-5p in astrocytomas is associated with a poor prognosis. The aim of the present study was to investigate the functional role of miR-181b-5p and its possible target genes. miR-181b-5p was significantly downregulated in astrocytoma specimens, and the reduced expression of miR-181b-5p was inversely correlated with the clinical stage. The ectopic expression of miR-181b-5p inhibited proliferation, migration and invasion and induced apoptosis in astrocytoma cancer cells in vitro. The NOVA1 (neuro-oncological ventral antigen 1) gene was further identified as a novel direct target of miR-181b-5p. Specifically, miR-181b-5p bound directly to the 3'-untranslated region (UTR) of NOVA1 and suppressed its expression. In clinical specimens, NOVA1 was overexpressed, and its protein levels were inversely correlated with miR-181b-5p expression. Furthermore, the changing level of NOVA1 was significantly associated with a poor survival outcome. Similar to restoring miR-181b-5p expression, downregulating NOVA1 inhibited cell growth, migration and invasion. Overexpression of NOVA1 reversed the inhibitory effects of miR-181b-5p. Our results indicate that miR-181b-5p is a tumor suppressor in astrocytoma that inhibits tumor progression by targeting NOVA1. These findings suggest that miR-181b-5p may serve as a novel therapeutic target for astrocytoma.

  16. Binding of NIR-conPK and NIR-6T to Astrocytomas and Microglial Cells: Evidence for a Protein Related to TSPO

    PubMed Central

    Sexton, Michelle; Woodruff, Grace; Cudaback, Eiron; Kreitzer, Faith R.; Xu, Cong; Lin, Yi Hsing; Möller, Thomas; Bai, Mingfeng; Manning, H. Charles; Bornhop, Darryl; Stella, Nephi

    2009-01-01

    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-γ (but not TNFα and TGFβ) 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 cytokines, and thus allows for

  17. Proton Beam Radiation Therapy in Treating Patients With Low Grade Gliomas

    ClinicalTrials.gov

    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

  18. Analysis of difference of association between polymorphisms in the XRCC5, RPA3 and RTEL1 genes and glioma, astrocytoma and glioblastoma

    PubMed Central

    Jin, Tianbo; Wang, Yuan; Li, Gang; Du, Shuli; Yang, Hua; Geng, Tingting; Hou, Peng; Gong, Yongkuan

    2015-01-01

    Background: Gliomas are the most common aggressive brain tumors and have many complex pathological types. Previous reports have discovered that genetic mutations are associated with the risk of glioma. However, it is unclear whether uniform genetic mutations exist difference between glioma and its two pathological types in the Han Chinese population. Materials and methods: We evaluated 20 SNPs of 703 glioma cases (338 astrocytoma cases, 122 glioblastoma cases) and 635 controls in a Han Chinese population using χ2 test and genetic model analysis. Results: In three case-control studies, we found rs9288516 in XRCC5 gene showed a decreased risk of glioma (OR, 0.85; 95% CI, 0.73-0.99; P = 0.042) and glioblastoma (OR, 0.70; 95% CI, 0.52-0.92; P = 0.001) in the allele model. We identified rs414805 in RPA3 gene showed an increased risk of glioblastoma in allele model (OR, 1.38; 95% CI, 1.00-1.89; P = 0.047) and dominant model (OR, 1.57; 95% CI, 1.05-2.35; P = 0.027), analysis respectively. Meanwhile, rs2297440 in RTEL1 gene showed an increased risk of glioma (OR, 1.30; 95% CI, 1.10-1.54; P = 0.002) and astrocytoma (OR, 1.26; 95% CI, 1.02-1.54; P = 0.029) in the allele model. In addition, we also observed a haplotype of “GCT” in the RTEL1 gene with an increased risk of astrocytoma (P = 0.005). Conclusions: Polymorphisms in the XRCC5, RPA3 and RTEL1 genes, combinating with previous reaserches, are associated with glioma developing. However, those genes mutations may play different roles in the glioma, astrocytoma and glioblastoma, respectively. PMID:26328260

  19. Deguelins, Natural Product Modulators of NF1-Defective Astrocytoma Cell Growth Identified by High-Throughput Screening of Partially Purified Natural Product Extracts.

    PubMed

    Henrich, Curtis J; Cartner, Laura K; Wilson, Jennifer A; Fuller, Richard W; Rizzo, Anthony E; Reilly, Karlyne M; McMahon, James B; Gustafson, Kirk R

    2015-11-25

    A high-throughput screening assay for modulators of Trp53/NF1 mutant astrocytoma cell growth was adapted for use with natural product extracts and applied to a novel collection of prefractionated/partially purified extracts. Screening 68 427 samples identified active fractions from 95 unique extracts, including the terrestrial plant Millettia ichthyotona. Only three of these extracts showed activity in the crude extract form, thus demonstrating the utility of a partial purification approach for natural product screening. The NF1 screening assay was used to guide purification of active compounds from the M. ichthyotona extract, which yielded the two rotenones deguelin (1) and dehydrodeguelin (2). The deguelins have been reported to affect growth of a number of cancer cell lines. They potently inhibited growth of only one of a panel of NF1/Trp53 mutant murine astrocytoma cell lines, possibly related to epigenetic factors, but had no effect on the growth of normal astrocytes. These results suggest the potential utility of deguelins as tools for further investigating NF1 astrocytoma cell growth. These bioprobes were identified only as a result of screening partially purified natural product extracts.

  20. Evaluation of the effect of treatment on movement disorders in astrocytomas of the basal ganglia and the thalamus.

    PubMed Central

    Krauss, J K; Braus, D F; Mohadjer, M; Nobbe, F; Mundinger, F

    1993-01-01

    Twenty patients with movement disorders associated with astrocytomas (grade I-IV according to the WHO tumour classification) of the basal ganglia and the thalamus were evaluated for the effects of treatment. Five patients had more than one movement disorder when the histological diagnosis was verified by stereotactic biopsy. Twelve had tremors, eight hemidystonia, three hemichorea, and one hemichorea/ballismus, and myoclonus respectively. Ten patients died during the follow up period, and for the surviving patients follow up periods ranged from 6-21 years. The movement disorders changed over long periods of time related to therapeutic interventions. CSF shunt operations and percutaneous radiotherapy had no definite effect on the movement disorders. There was a moderate response to medical treatment in a few patients. Stereotactic aspiration of tumour cysts had a marked influence on the movement disorder in two patients, and functional stereotactic surgery abolished tumour induced tremor in one. Interstitial radiotherapy was performed in fifteen patients for treatment of the underlying neoplasm and resulted in different and variable alterations of the movement disorders. These differences may be explained by complex interactions involving structures affected primarily by the tumour, as well as by secondary functional lesions of adjacent structures. Images PMID:8410011

  1. Neutral metoclopramide sensitizes cytotoxicity induced by ionizing radiation in SCID mice xenografted with a human brain astrocytoma.

    PubMed

    Hua, J; Olsson, A R; Pero, R W

    1997-12-10

    A formulation of metoclopramide (MCA) conformationally altered by neutralization of pH (nMCA, Neu-Sensamide) has been shown to have the same efficacy of enhancing the cytotoxicity of a single dose of 1 Gy radiation as acidic formulations (e.g., Primperan, Sensamide) in a human lung adenocarcinoma (H2981) xenografted into SCID mice. In the present study, 2 x 1 Gy radiation was combined with 2 x 2 mg nMCA/kg body weight injected 2 hr before radiation treatment for evaluation of radiosensitization in SCID mice xenografted with a human brain astrocytoma (T24). Given in this treatment schedule, nMCA alone at 2 mg/kg showed no cytotoxic effect on tumor growth in vivo. When combined with 2 x 1 Gy of radiation, however, the cytotoxicity was significantly increased as measured by tumor growth delay over the radiation-only-treated group. Furthermore, nMCA was absorbed into brains of mice and rats as efficiently as acidic MCA (aMCA) when analyzed 45 min after i.m. injection by high-performance liquid chromatography.

  2. Hypofractionated high-dose irradiation for the treatment of malignant astrocytomas using simultaneous integrated boost technique by IMRT

    SciTech Connect

    Iuchi, Toshihiko; Hatano, Kazuo; Narita, Yuichiro; Kodama, Takashi; Yamaki, Tomohiro; Osato, Katsunobu

    2006-04-01

    Purpose: We evaluated the clinical significance of hypofractionated high-dose irradiation using simultaneous integrated boost technique with intensity-modulated radiation therapy (IMRT) for the treatment of malignant astrocytomas (MAs). Methods and Materials: Twenty-five patients with MAs were treated by IMRT. Three layered planning target volumes (PTVs) were contoured. PTV-1 was the area of enhanced lesion with 5-mm margin; PTV-2 was the area with 15-mm margin surrounding the PTV-1; PTV-3 was the area of perifocal edema. Irradiation was performed in 8 fractions, and only the dose for PTV-1 was escalated from 48 Gy to 68 Gy while maintaining the dose for PTV-2 (40 Gy) and PTV-3 (32 Gy). The clinical outcome of IMRT was compared with 60 MA patients treated by conventional external beam irradiation (EBI). Results: The progression-free survival of patients in the IMRT group was significantly longer than that in the EBI group (p < 0.0001). No distant failure was observed in both groups. In the IMRT group, dissemination was the most frequent cause of death (70%). The overall survival of patients in the IMRT group was better than that in the EBI group (p = 0.043). Conclusions: Our regimen of IMRT contributed to the control of both the regional and infiltrating tumors, resulting in better survival of patients.

  3. Dysphasia and Phantosmia as First Presentation of Multifocal Cerebral Anaplastic Astrocytomas: Case Report and Review of the Literatures

    PubMed Central

    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

    2015-01-01

    Abstract 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 <4 lesions supratentorially, and are lack of typical symptoms and special detections. Through a rare MCG case, we aim to present this rarity and emphasize the need to correctly diagnose multiple intracranial lesions using a variety of diagnostic modalities to ensure that the patient receives proper treatment. We present a case of multifocal cerebral anaplastic astrocytomas with a total of 8 lesions located in the left frontal lobe and invading the lateral ventricle, presenting 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. PMID:25997068

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

    SciTech Connect

    Godin, Fabienne; Villette, Sandrine; Vallee, Beatrice; Doudeau, Michel; Morisset-Lopez, Severine; Ardourel, Maryvonne; Hevor, Tobias; Pichon, Chantal; Benedetti, Helene

    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).

  5. Intrinsic tectal low grade astrocytomas: is surgical removal an alternative treatment? Long-term outcome of eight cases.

    PubMed

    Ramina, Ricardo; Coelho Neto, Mauricio; Fernandes, Yvens Barbosa; Borges, Guilherme; Honorato, Donizeti Cesar; Arruda, Walter Oleschko

    2005-03-01

    Low-grade gliomas arising in dorsal midbrain in children and young patients usually present few neurological symptoms and findings, and patients management is controversial. Some authors propose only clinical observation until the patient present signs of increased intracranial pressure when a shunt with or without biopsy, is inserted; others recommend radiotherapy after stereotactic or open biopsy. Microsurgical total removal of tumor may be curative. We present a retrospective analysis of eight patients (mean age 16.6 +/- 11.5 years-old) with low-grade astrocytoma of the tectal region operated on using an infratentorial/supracerebellar approach between 1981 and 2002. All patients presented hydrocephalus and had a shunt insertion before surgical resection of the lesion. The tumour could be totally resected in seven patients. In one case radical removal was not possible due to infiltrative pattern of the lesion. Postoperative radiotherapy was performed in two cases, one patient at the beginning of this series and in the case with infiltrative tumor. This patient presented progressive tumor growth and died five years after surgery. No recurrence occurred after total removal. Post-surgical follow-up time ranged from 2 1/2 to 22 1/2 years (mean 9.9 +/- 5.9 years). Radical microsurgical removal of non invasive tumors is possible without mortality or significant morbidity. It may be curative and should remain as an alternative to be discussed with the patient.

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

    PubMed

    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.

  7. Elevated levels of p-Mnk1, p-eIF4E and p-p70S6K proteins are associated with tumor recurrence and poor prognosis in astrocytomas.

    PubMed

    Fan, Weibing; Wang, Weiyuan; Mao, Xinfa; Chu, Shuzhou; Feng, Juan; Xiao, Desheng; Zhou, Jianhua; Fan, Songqing

    2017-02-01

    Malignant astrocytomas are able to invade neighboring and distant areas of the normal brain. Signaling pathway alterations play important role in the development of astrocytomas. Deregulation of eukaryotic translation initiation factor 4E (eIF4E) by MAP kinase-interacting kinases (Mnk) on Ser-209 directly or PI3K/mTOR/S6K pathway indirectly has a critical effect on promoting cellular proliferation, malignant transformation and metastasis. We examined and analyzed the correlation between expression of p-Mnk1, p-eIF4E and p-p70S6K proteins and clinicopathological features in 103 astrocytomas and 54 non-tumorous brain tissues. The results indicated that positive percentage of overexpression of p-Mnk1 and p-eIF4E proteins in astrocytomas were significantly higher than that of in the non-tumorous brain tissues (P < 0.05). Elevated p-Mnk1 and p-eIF4E and co-overexpressed three proteins were associated with tumor recurrence (P = 0.003, P = 0.006, P = 0.007, respectively). Overexpressed p-eIF4E significantly correlated with the tumor size (P = 0.019). In addition, overexpression of p-eIF4E and three proteins common expression were related to the WHO grade of astrocytomas (P = 0.001, P = 0.044 respectively). Spearman's rank correlation test further showed that the expression of p-Mnk1 was strongly positive correlated with the expression of p-eIF4E in astrocytomas (r = 0.294, P = 0.003). Besides, overexpression of p-eIF4E and co-expression of p-Mnk1, p-eIF4E and p-p70S6K proteins were inversely correlated with overall survival rates of astrocytomas. Multivariate Cox regression analysis further identified that the elevated p-eIF4E expression, three proteins common expression were correlated with unfavorable prognosis of astrocytomas regardless of ages and WHO grades. Taken together, overexpression of p-eIF4E and co-expression of p-Mnk1, p-eIF4E and p-p70S6K proteins could be used as novel independent poor prognostic biomarkers for patients

  8. Yes-associated protein 1 is widely expressed in human brain tumors and promotes glioblastoma growth.

    PubMed

    Orr, Brent A; Bai, Haibo; Odia, Yazmin; Jain, Deepali; Anders, Robert A; Eberhart, Charles G

    2011-07-01

    The hippo pathway and its downstream mediator yes-associated protein 1 (YAP1) regulate mammalian organ size in part through modulating progenitor cell numbers. YAP1 has also been implicated as an oncogene in multiple human cancers. Currently, little is known about the expression of YAP1 either in normal human brain tissue or in central nervous system neoplasms. We used immunohistochemistry to evaluate nuclear YAP1 expression in the fetal and normal adult human brains and in 264 brain tumors. YAP1 was expressed in fetal and adult brain regions known to harbor neural progenitor cells, but there was little YAP1 immunoreactivity in the adult cerebral cortex. YAP1 protein was also readily detected in the nuclei of human brain tumors. In medulloblastoma, the expression varied between histologic subtypes and was most prominent in nodular/desmoplastic tumors. In gliomas, it was frequently expressed in infiltrating astrocytomas and oligodendrogliomas but rarely in pilocytic astrocytomas. Using a loss-of-function approach, we show that YAP1 promoted growth of glioblastoma cell lines in vitro. High levels of YAP1 messenger RNA expression were associated with aggressive molecular subsets of glioblastoma and with a nonsignificant trend toward reduced mean survival in human astrocytoma patients. These findings suggest that YAP1 may play an important role in normal human brain development and that it could represent a new target in human brain tumors.

  9. Comparative non-cholinergic neurotoxic effects of paraoxon and diisopropyl fluorophosphate (DFP) on human neuroblastoma and astrocytoma cell lines

    SciTech Connect

    Qian Yongchang; Venkatraj, Jijayanagaram; Barhoumi, Rola; Pal, Ranadip; Datta, Aniruddha; Wild, James R.; Tiffany-Castiglioni, Evelyn . E-mail: ecastiglioni@cvm.tamu.edu

    2007-03-15

    The objective of this study was to evaluate the comparative non-cholinergic neurotoxic effects of paraoxon, which is acutely neurotoxic, and diisopropyl fluorophosphate (DFP), which induces OPIDN, in the human neuroblastoma SY5Y and the human astrocytoma cell line CCF-STTG1. SY5Y cells have been studied extensively as a model for OP-induced neurotoxicity, but CCF cells have not previously been studied. We conducted a preliminary human gene array assay of OP-treated SY5Y cells in order to assess at the gene level whether these cells can distinguish between OP compounds that do and do not cause OPIDN. Paraoxon and DFP induced dramatically different profiles of gene expression. Two genes were upregulated and 13 downregulated by at least 2-fold in paraoxon-treated cells. In contrast, one gene was upregulated by DFP and none was downregulated at the 2-fold threshold. This finding is consistent with current and previous observations that SY5Y cells can distinguish between OPs that do or do not induce OPIDN. We also examined gene array results for possible novel target proteins or metabolic pathways for OP neurotoxicity. Protein levels of glucose regulated protein 78 (GRP78) revealed that paraoxon exposure at 3 {mu}M for 24 h significantly reduced GRP78 levels by 30% in neuroblastoma cells, whereas DFP treatment had no effect. In comparison with SY5Y neuroblastoma cells, paraoxon and DFP (3 {mu}M for 24 h) each significantly increased GRP78 levels by 23-24% in CCF astrocytoma cells. As we have previously evaluated intracellular changes in Ca{sup 2+} levels in SY5Y cells, we investigated the effects of paraoxon and DFP on cellular Ca{sup 2+} homeostasis in CCF by studying cytosolic and mitochondrial basal calcium levels. A significant decrease in the ratio of mitochondrial to cytosolic Ca{sup 2+} fluorescence was detected in CCF cultures treated for either 1 or 3 days with 1, 3, 10, or 30 {mu}M paraoxon. In contrast, treatment with DFP for 1 day had no significant effect

  10. Network analysis of microRNAs, transcription factors, target genes and host genes in human anaplastic astrocytoma

    PubMed Central

    XUE, LUCHEN; XU, ZHIWEN; WANG, KUNHAO; WANG, NING; ZHANG, XIAOXU; WANG, SHANG

    2016-01-01

    Numerous studies have investigated the roles played by various genes and microRNAs (miRNAs) in neoplasms, including anaplastic astrocytoma (AA). However, the specific regulatory mechanisms involving these genes and miRNAs remain unclear. In the present study, associated biological factors (miRNAs, transcription factors, target genes and host genes) from existing studies of human AA were combined methodically through the interactions between genes and miRNAs, as opposed to studying one or several. Three regulatory networks, including abnormally expressed, related and global networks were constructed with the aim of identifying significant gene and miRNA pathways. Each network is composed of three associations between miRNAs targeted at genes, transcription factors (TFs) regulating miRNAs and miRNAs located on their host genes. Among these, the abnormally expressed network, which involves the pathways of previously identified abnormally expressed genes and miRNAs, partially indicated the regulatory mechanism underlying AA. The network contains numerous abnormal regulation associations when AA emerges. By modifying the abnormally expressed network factors to a normal expression pattern, the faulty regulation may be corrected and tumorigenesis of AA may be prevented. Certain specific pathways are highlighted in AA, for example PTEN which is targeted by miR-21 and miR-106b, regulates miR-25 which in turn targets TP53. PTEN and miR-21 have been observed to form feedback loops. Furthermore, by comparing and analyzing the pathway predecessors and successors of abnormally expressed genes and miRNAs in three networks, similarities and differences of regulatory pathways may be identified and proposed. In summary, the present study aids in elucidating the occurrence, mechanism, prevention and treatment of AA. These results may aid further investigation into therapeutic approaches for this disease. PMID:27347075

  11. The interaction of bee products with temozolomide in human diffuse astrocytoma, glioblastoma multiforme and astroglia cell lines.

    PubMed

    Borawska, Maria H; Markiewicz-Żukowska, Renata; Naliwajko, Sylwia K; Moskwa, Justyna; Bartosiuk, Emilia; Socha, Katarzyna; Surażyński, Arkadiusz; Kochanowicz, Jan; Mariak, Zenon

    2014-01-01

    In the present study, we investigated the influence of extracts from Salix spp. honey (ESH), beebread (EBB), and royal jelly (ERJ) with and without temozolomide (TMZ) on cell lines derived from a patient with diffuse astrocytoma (DASC), human glioblastoma multiforme (U87MG), and normal human astroglia (SVGp12). DASC was identified by immunocytochemistry. TMZ (20 μM) in combination with ESH (30 μg/mL), EBB (50 μg/mL), and ERJ (30 μg/mL) has stronger cytotoxic activity on U87MG cells after 72 h (20.0, 26.5, and 29.3% of control, respectively) than TMZ alone (about 6% of control). An increase of the cytotoxic effect and inhibition of DNA synthesis in SVGp12 were detected after administering TMZ with the studied extracts. NF-κB p50 subunit was reduced in U87MG cells after treatment with ESH (70.9%) and ESH + TMZ (74.7%). A significant decline of MMP-9 and MMP-2 secretion in cultured U87MG was detected after incubation with EBB (42.9% and 73.0%, respectively) and EBB + TMZ (38.4% and 68.5%, respectively). In conclusion, the use of bee products may increase the cytotoxic effect of TMZ in U87MG but also in SVGp12 cell line. It is important to note that the U87MG cells were sensitive to natural bee products, although there was no influence of natural bee products on the DASC cells.

  12. Assessment and prognostic significance of mitotic index using the mitosis marker phospho-histone H3 in low and intermediate-grade infiltrating astrocytomas.

    PubMed

    Colman, Howard; Giannini, Caterina; Huang, Li; Gonzalez, Javier; Hess, Kenneth; Bruner, Janet; Fuller, Gregory; Langford, Lauren; Pelloski, Christopher; Aaron, Joann; Burger, Peter; Aldape, Ken

    2006-05-01

    Distinguishing between grade II and grade III diffuse astrocytomas is important both for prognosis and for treatment decision-making. However, current methods for distinguishing between grades based on proliferative potential are suboptimal, making identification of clear cutoffs difficult. In this study, we compared the results from immunohistochemical staining for phospho-histone H3 (pHH3), a specific marker of cells undergoing mitosis, with standard mitotic counts (number of mitoses/10 high-power fields) and MIB-1 labeling index values for assessing proliferative activity. We tested the relationship between pHH3 staining and tumor grade and prognosis in a retrospective series of grade II and III infiltrating astrocytomas from a single institution. The pHH3 index (per 1000 cells), MIB-1 index (per 1000 cells), and number of mitoses per 10 high-power fields were determined for each of 103 cases of grade II and III diffuse astrocytomas from patients with clinical follow-up. pHH3 staining was found to be a simple and reliable method for identifying mitotic figures, allowing a true mitotic index to be determined. The pHH3 mitotic index was significantly associated both with the standard mitotic count and with the MIB-1 index. Univariate analyses revealed that all 3 measurements of proliferation were significantly associated with survival. However, the pHH3 mitotic index accounted for a larger proportion of variability in survival than standard mitotic count or MIB-1/Ki-67 labeling index. After adjusting for age, extent of resection, and performance score, the pHH3 mitotic index remained an independent predictor of survival. Thus, pHH3 staining provides a simple and reliable method for quantifying proliferative potential and for the stratification of patients with diffuse astrocytomas into typical grade II and III groups. These results also suggest that pHH3 staining may be a useful method in other neoplasms in which accurate determination of proliferation potential

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed

    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.

  16. Bevacizumab and Cediranib Maleate in Treating Patients With Metastatic or Unresectable Solid Tumor, Lymphoma, Intracranial Glioblastoma, Gliosarcoma or Anaplastic Astrocytoma

    ClinicalTrials.gov

    2014-02-14

    Adult Grade III Lymphomatoid Granulomatosis; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Childhood Burkitt Lymphoma; Childhood Diffuse Large Cell Lymphoma; Childhood Grade III Lymphomatoid Granulomatosis; Childhood Immunoblastic Large Cell Lymphoma; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Progressive Hairy Cell Leukemia, Initial Treatment; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Adult T-cell Leukemia/Lymphoma; Stage IV Childhood Anaplastic Large Cell Lymphoma; Stage IV Childhood Hodgkin Lymphoma; Stage IV

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

    PubMed

    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.

  18. Superoxide anion radical (O2(-)) degrades methylmercury to inorganic mercury in human astrocytoma cell line (CCF-STTG1).

    PubMed

    Mailloux, Ryan J; Yumvihoze, Emmanuel; Chan, Hing Man

    2015-09-05

    Methylmercury (MeHg) is a global pollutant that is affecting the health of millions of people worldwide. However, the mechanism of MeHg toxicity still remains somewhat elusive and there is no treatment. It has been known for some time that MeHg can be progressively converted to inorganic mercury (iHg) in various tissues including the brain. Recent work has suggested that cleavage of the carbon-metal bond in MeHg in a biological environment is facilitated by reactive oxygen species (ROS). However, the oxyradical species that actually mediates this process has not been identified. Here, we provide evidence that superoxide anion radical (O2(-)) can convert MeHg to iHg. The calculated second-order rate constant for the degradation of 1μM MeHg by O2(-) generated by xanthine/xanthine oxidase was calculated to be 2×10(5)M(-1)s(-1). We were also able to show that this bioconversion can proceed in intact CCF-STTG1 human astrocytoma cells exposed to paraquat (PQ), a O2(-) generating viologen. Notably, exposure of cells to increasing amounts of PQ led to a dose dependent increase in both MeHg and iHg. Indeed, a 24h exposure to 500μM PQ induced a ∼13-fold and ∼18-fold increase in intracellular MeHg and iHg respectively. These effects were inhibited by superoxide dismutase mimetic MnTBAP. In addition, we also observed that a 24h exposure to a biologically relevant concentration of MeHg (1μM) did not induce cell death, oxidative stress, or even changes in cellular O2(-) and H2O2. However, co-exposure to PQ enhanced MeHg toxicity which was associated with a robust increase in cell death and oxidative stress. Collectively our results show that O2(-) can bioconvert MeHg to iHg in vitro and in intact cells exposed to conditions that simulate high intracellular O2(-) production. In addition, we show for the first time that O2(-) mediated degradation of MeHg to iHg enhances the toxicity of MeHg by facilitating an accumulation of both MeHg and iHg in the intracellular

  19. Understanding inherited genetic risk of adult glioma – a review

    PubMed Central

    Rice, Terri; Lachance, Daniel H.; Molinaro, Annette M.; Eckel-Passow, Jeanette E.; Walsh, Kyle M.; Barnholtz-Sloan, Jill; Ostrom, Quinn T.; Francis, Stephen S.; Wiemels, Joseph; Jenkins, Robert B.; Wiencke, John K.; Wrensch, Margaret R.

    2016-01-01

    During the past six years, researchers have made major progress identifying common inherited genetic variation that increases risk for primary adult glioma. This paper summarizes knowledge about rare familial cancer syndromes that include adult glioma and reviews the available literature on the more recently discovered common inherited variation. Ten independent inherited variants in eight chromosomal regions have been convincingly associated with increased risk for adult glioma. Most of these variants increase relative risk of primary adult glioma by 20% to 40%, but the TP53 variant rs78378222 confers a two-fold relative risk (ie, 200%), and rs557505857 on chromosome 8 confers a six-fold relative risk of IDH-mutated astrocytomas and oligodendroglial tumors (ie, 600%). Even with a six-fold relative risk, the overall risk of developing adult glioma is too low for screening for the high-risk variant on chromosome 8. Future studies will help clarify which inherited adult glioma risk variants are associated with subtypes defined by histology and/or acquired tumor mutations. This review also provides an information sheet for primary adult glioma patients and their families. PMID:26941959

  20. Understanding inherited genetic risk of adult glioma - a review.

    PubMed

    Rice, Terri; Lachance, Daniel H; Molinaro, Annette M; Eckel-Passow, Jeanette E; Walsh, Kyle M; Barnholtz-Sloan, Jill; Ostrom, Quinn T; Francis, Stephen S; Wiemels, Joseph; Jenkins, Robert B; Wiencke, John K; Wrensch, Margaret R

    2016-03-01

    During the past six years, researchers have made major progress identifying common inherited genetic variation that increases risk for primary adult glioma. This paper summarizes knowledge about rare familial cancer syndromes that include adult glioma and reviews the available literature on the more recently discovered common inherited variation. Ten independent inherited variants in eight chromosomal regions have been convincingly associated with increased risk for adult glioma. Most of these variants increase relative risk of primary adult glioma by 20% to 40%, but the TP53 variant rs78378222 confers a two-fold relative risk (ie, 200%), and rs557505857 on chromosome 8 confers a six-fold relative risk of IDH-mutated astrocytomas and oligodendroglial tumors (ie, 600%). Even with a six-fold relative risk, the overall risk of developing adult glioma is too low for screening for the high-risk variant on chromosome 8. Future studies will help clarify which inherited adult glioma risk variants are associated with subtypes defined by histology and/or acquired tumor mutations. This review also provides an information sheet for primary adult glioma patients and their families.

  1. Regulation of sonic hedgehog-GLI1 downstream target genes PTCH1, Cyclin D2, Plakoglobin, PAX6 and NKX2.2 and their epigenetic status in medulloblastoma and astrocytoma

    PubMed Central

    2010-01-01

    Background The Sonic hedgehog (Shh) signaling pathway is critical for cell growth and differentiation. Impairment of this pathway can result in both birth defects and cancer. Despite its importance in cancer development, the Shh pathway has not been thoroughly investigated in tumorigenesis of brain tumors. In this study, we sought to understand the regulatory roles of GLI1, the immediate downstream activator of the Shh signaling pathway on its downstream target genes PTCH1, Cyclin D2, Plakoglobin, NKX2.2 and PAX6 in medulloblastoma and astrocytic tumors. Methods We silenced GLI1 expression in medulloblastoma and astrocytic cell lines by transfection of siRNA against GLI1. Subsequently, we performed RT-PCR and quantitative real time RT-PCR (qRT-PCR) to assay the expression of downstream target genes PTCH1, Cyclin D2, Plakoglobin, NKX2.2 and PAX6. We also attempted to correlate the pattern of expression of GLI1 and its regulated genes in 14 cell lines and 41 primary medulloblastoma and astrocytoma tumor samples. We also assessed the methylation status of the Cyclin D2 and PTCH1 promoters in these 14 cell lines and 58 primary tumor samples. Results Silencing expression of GLI1 resulted up-regulation of all target genes in the medulloblastoma cell line, while only PTCH1 was up-regulated in astrocytoma. We also observed methylation of the cyclin D2 promoter in a significant number of astrocytoma cell lines (63%) and primary astrocytoma tumor samples (32%), but not at all in any medulloblastoma samples. PTCH1 promoter methylation was less frequently observed than Cyclin D2 promoter methylation in astrocytomas, and not at all in medulloblastomas. Conclusions Our results demonstrate different regulatory mechanisms of Shh-GLI1 signaling. These differences vary according to the downstream target gene affected, the origin of the tissue, as well as epigenetic regulation of some of these genes. PMID:21059263

  2. Prognostic value of the extent of resection in supratentorial WHO grade II astrocytomas stratified for IDH1 mutation status: a single-center volumetric analysis.

    PubMed

    Jungk, Christine; Scherer, Moritz; Mock, Andreas; Capper, David; Radbruch, Alexander; von Deimling, Andreas; Bendszus, Martin; Herold-Mende, Christel; Unterberg, Andreas

    2016-09-01

    Current evidence supports a maximized extent of resection (EOR) in low-grade gliomas (LGG), regardless of different histological subtypes and molecular markers. We therefore evaluated the prognostic impact of extensive, mainly intraoperative (i)MRI-guided surgery in low-grade astrocytomas stratified for IDH1 mutation status. Retrospective assessment of 46 consecutive cases of newly diagnosed supratentorial WHO grade II astrocytomas treated during the last decade was performed. IDH1 mutation status was obtained for all patients. Volumetric analysis of tumor volumes was performed pre-, intra-, early postoperatively and at first follow-up. Survival analysis was conducted with uni-and multivariate regression models implementing clinical parameters and continuous volumetric variables. Median EOR was 90.4 % (range 17.5-100 %) and was increased to 94.9 % (range 34.8-100 %) in iMRI-guided resections (n = 33). A greater EOR was prognostic for increased progression-free survival (HR 0.23, p = 0.031) and time to re-intervention (TTR) (HR 0.23, p = 0.03). In IDH1 mutant patients, smaller residual tumor volumes were associated with increased TTR (HR 1.01, p = 0.03). IDH1 mutation (38/46 cases) was an independent positive prognosticator for overall survival (OS) in multivariate analysis (HR 0.09, p = 0.002), while extensive surgery had limited impact upon OS. In a subgroup of patients with ≥40 % EOR (n = 39), however, initial and residual tumor volumes were prognostic for OS (HR 1.03, p = 0.005 and HR 1.08, p = 0.007, respectively), persistent to adjustment for IDH1. No association between EOR and neurologic morbidity was found. In this analysis of low-grade astrocytomas stratified for IDH1, extensive tumor resections were prognostic for progression and TTR and, in patients with ≥40 % EOR, for OS.

  3. Childhood Astrocytomas Treatment

    MedlinePlus

    ... before the cancer is diagnosed and continue for months or years. Signs or symptoms caused by the ... after treatment. Some cancer treatments cause side effects months or years after treatment has ended. Side effects ...

  4. Effects of La0.2Ce0.6Eu0.2F3 nanoparticles capped with polyethylene glycol on human astrocytoma cells in vitro

    NASA Astrophysics Data System (ADS)

    Withers, Nathan J.; Brandt, Yekaterina; Rivera, Antonio C.; Armijo, Leisha M.; Cook, Nathaniel C.; Osiński, Marek

    2012-03-01

    Lanthanide fluoride colloidal nanocrystals offer a way to improve the diagnosis and treatment of cancer through the enhanced absorption of ionizing radiation, as well as providing visible luminescence. In order to explore this possibility, cytotoxicity assays need to be performed on mammalian cells in vitro, to show minimum levels of biocompatibility for future experiments. 20% lanthanum 60% cerium and 20% europium lanthanide fluoride nanocrystals were capped with polyethylene glycol (PEG) of molecular weight 4000 and suspended in deionized water. These nanocrystals were characterized by transmission electron microscopy, muffle furnace ashing, absorbance spectroscopy, dynamic light scattering, and photoluminescence spectroscopy. Visible light microscopy and trypan blue staining was performed on the cells to assay the cytotoxicity of the nanocrystal on the human astrocytoma line U-87 MG, purchased from ATCC.

  5. Guanine nucleotide-dependent, pertussis toxin-insensitive, stimulation of inositol phosphate formation by carbachol in a membrane preparation from astrocytoma cells

    SciTech Connect

    Hepler, J.R.; Harden, T.K.

    1986-03-05

    Formation of the inositol phosphates (InsP), InsP/sub 3/, InsP/sub 2/, and InsP/sub 1/ was increased in a concentration dependent manner (K/sub 0.5/ approx. 5 ..mu..M) by GTP..sigma..S in washed membranes prepared from /sup 3/H-inositol-prelabelled 1321N1 human astrocytoma cells. Both GTP..gamma..S and GppNHp stimulated InsP formation by 2-3 fold over control; GTP and GDP were much less efficacious and GMP had no effect. Although the muscarinic cholinergic receptor agonist carbachol had no effect in the absence of guanine nucleotide, in the presence of 10 ..mu..M GTP..gamma..S, carbachol stimulated (K/sub 0.5/ approx. 10 ..mu.. M) the formation of InsP above the level achieved with GTP..gamma..S alone. The effect of carbachol was completely blocked by atropine. The order of potency for a series of nucleotides for stimulation of InsP formation in the presence of 500 ..mu..M carbachol was GTP..gamma..S > GppNHp > GTP = GDP. Pertussis toxin, at concentrations that fully ADP-ribosylate and functionally inactivate G/sub i/, had no effect on InsP formation in the presence of GTP..gamma..S or GTP..gamma..S plus carbachol. Histamine and bradykinin also stimulated InsP formation in the presence of GTP..gamma..S in washed membranes from 1321N1 cells. These data are consistent with the idea that a guanine nucleotide regulatory protein that is not G/sub i/ is involved in receptor-mediated stimulation of InsP formation in 1321N1 human astrocytoma cells.

  6. Cytosolic phospholipase A2 is coupled to muscarinic receptors in the human astrocytoma cell line 1321N1: characterization of the transducing mechanism.

    PubMed Central

    Bayon, Y; Hernandez, M; Alonso, A; Nuñez, L; Garcia-Sancho, J; Leslie, C; Sanchez Crespo, M; Nieto, M L

    1997-01-01

    The cholinergic agonist carbachol induced the release of arachidonic acid in the 1321N1 astrocytoma cell line, and this was blocked by atropine, suggesting the involvement of muscarinic receptors. To assess the mechanisms of signalling involved in the response to carbachol, a set of compounds characterized by eliciting responses through different mechanisms was tested. A combination of 4beta-phorbol 12beta-myristate 13alpha-acetate and thapsigargin, an inhibitor of endomembrane Ca2+-ATPase that induces a prolonged elevation of cytosolic Ca2+ concentration, induced an optimal response, suggesting at first glance that both protein kinase C (PKC) and Ca2+ mobilization were involved in the response. This was consistent with the observation that carbachol elicited Ca2+ mobilization and PKC-dependent phosphorylation of cytosolic phospholipase A2 (cPLA2; phosphatide sn-2-acylhydrolase, EC 3.1.1.4) as measured by a decrease in electrophoretic mobility. Nevertheless, the release of arachidonate induced by carbachol was unaltered in media containing decreased concentrations of Ca2+ or in the presence of neomycin, a potent inhibitor of phospholipase C which blocks phosphoinositide turnover and Ca2+ mobilization. Guanosine 5'-[gamma-thio]triphosphate added to the cell-free homogenate induced both [3H]arachidonate release and cPLA2 translocation to the cell membrane fraction in the absence of Ca2+, thus suggesting the existence of an alternative mechanism of cPLA2 translocation dependent on G-proteins and independent of Ca2+ mobilization. From the combination of experiments utilizing biochemical and immunological tools the involvement of cPLA2 was ascertained. In summary, these data indicate the existence in the astrocytoma cell line 1321N1 of a pathway involving the cPLA2 which couples the release of arachidonate to the occupancy of receptors for a neurotransmitter, requires PKC activity and G-proteins and might operate in the absence of Ca2+ mobilization. PMID:9173894

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

    PubMed Central

    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 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. PMID:25325361

  8. Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma.

    PubMed

    Ceccarelli, Michele; Barthel, Floris P; Malta, Tathiane M; Sabedot, Thais S; Salama, Sofie R; Murray, Bradley A; Morozova, Olena; Newton, Yulia; Radenbaugh, Amie; Pagnotta, Stefano M; Anjum, Samreen; Wang, Jiguang; Manyam, Ganiraju; Zoppoli, Pietro; Ling, Shiyun; Rao, Arjun A; Grifford, Mia; Cherniack, Andrew D; Zhang, Hailei; Poisson, Laila; Carlotti, Carlos Gilberto; Tirapelli, Daniela Pretti da Cunha; Rao, Arvind; Mikkelsen, Tom; Lau, Ching C; Yung, W K Alfred; Rabadan, Raul; Huse, Jason; Brat, Daniel J; Lehman, Norman L; Barnholtz-Sloan, Jill S; Zheng, Siyuan; Hess, Kenneth; Rao, Ganesh; Meyerson, Matthew; Beroukhim, Rameen; Cooper, Lee; Akbani, Rehan; Wrensch, Margaret; Haussler, David; Aldape, Kenneth D; Laird, Peter W; Gutmann, David H; Noushmehr, Houtan; Iavarone, Antonio; Verhaak, Roel G W

    2016-01-28

    Therapy development for adult diffuse glioma is hindered by incomplete knowledge of somatic glioma driving alterations and suboptimal disease classification. We defined the complete set of genes associated with 1,122 diffuse grade II-III-IV gliomas from The Cancer Genome Atlas and used molecular profiles to improve disease classification, identify molecular correlations, and provide insights into the progression from low- to high-grade disease. Whole-genome sequencing data analysis determined that ATRX but not TERT promoter mutations are associated with increased telomere length. Recent advances in glioma classification based on IDH mutation and 1p/19q co-deletion status were recapitulated through analysis of DNA methylation profiles, which identified clinically relevant molecular subsets. A subtype of IDH mutant glioma was associated with DNA demethylation and poor outcome; a group of IDH-wild-type diffuse glioma showed molecular similarity to pilocytic astrocytoma and relatively favorable survival. Understanding of cohesive disease groups may aid improved clinical outcomes.

  9. Cerebral astroblastoma: A radiopathological diagnosis

    PubMed Central

    Singh, Deepak Kumar; Singh, Neha; Singh, Ragini; Husain, Nuzhat

    2014-01-01

    Astroblastoma is a rare glial neoplasm whose histogenesis has been clarified recently. It primarily occurs in children and young adults. We are reporting a case of 12-year-old girl child who presented with features of raised intracranial tension and generalized tonic-clonic seizures. Brain magnetic resonance imaging revealed a large well-circumscribed, cystic lesion without perifocal edema, and enhancing mural nodule in right parietal region. A radiological differential diagnosis of pilocytic astrocytoma and cerebral astroblastoma was made. A complete excision was done and histologically the lesion turned out to be an astroblastoma. We review the histology, immunohistochemistry, and imaging features of astroblastoma and survey the current literature, treatment strategies, and prognostic aspects for the management of this rare neoplasm. PMID:24891904

  10. Yoga Therapy in Treating Patients With Malignant Brain Tumors

    ClinicalTrials.gov

    2017-01-17

    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

  11. Gadobutrol Versus Gadopentetate Dimeglumine or Gadobenate Dimeglumine Before DCE-MRI in Diagnosing Patients With Multiple Sclerosis, Grade II-IV Glioma, or Brain Metastases

    ClinicalTrials.gov

    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

  12. Guggulipid and nimesulide differentially regulated inflammatory genes mRNA expressions via inhibition of NF-kB and CHOP activation in LPS-stimulated rat astrocytoma cells, C6.

    PubMed

    Niranjan, Rituraj; Nath, Chandishwar; Shukla, Rakesh

    2011-07-01

    Neuroinflammation is an integral part of neurodegenerative diseases. Lipo-polysacharide (LPS) induces reactive astrogliosis, the cellular manifestation of neuroinflammation, in various models of neurological diseases, but its mechanism of action is still not properly known. The effect of guggulipid and nimesulide on LPS-induced neuroinflammatory changes is also not properly understood. This work demonstrated the mechanism of actions of guggulipid and nimesulide on inflammatory genes expressions in LPS-stimulated rat astrocytoma cells, C6. We observed that LPS (10 μg/ml) treatment of rat astrocytoma cells, C6, for 24 h significantly increased intracellular Ca(2+) ion and expression of inducible nitric oxide synthase (iNOS), nuclear factor kappa-B (NF-kB), C/EBP homologous protein 10 (CHOP), c-fos, and c-jun proteins. At transcriptional stage, LPS upregulated mRNA levels of cyclooxygenase-2 and IL-6 with downregulation in IL-1α, IL-1β, and microsomal prostaglandin E synthase-1 (mPGES-1) through activating NF-kB translocation. Treatment with guggulipid reversed these LPS-induced changes in rat astrocytoma cells. Treatment with nimesulide also attenuated LPS-induced Ca(2+) ion, iNOS, NF-kB, and c-fos expressions, but does not significantly influence CHOP, c-jun protein expressions, and mRNA levels of IL-6, IL-1α, IL-1β, and mPGES-1 genes. In conclusion, our findings elucidated the molecular mechanism of neuroinflammation in response to LPS and its modulation by guggulipid and nimesulide in rat astrocytoma cells (C6), which suggest the use of these drugs in the treatment of neuroinflammation-associated disorders.

  13. Adult infiltrating gliomas with WHO 2016 integrated diagnosis: additional prognostic roles of ATRX and TERT.

    PubMed

    Pekmezci, Melike; Rice, Terri; Molinaro, Annette M; Walsh, Kyle M; Decker, Paul A; Hansen, Helen; Sicotte, Hugues; Kollmeyer, Thomas M; McCoy, Lucie S; Sarkar, Gobinda; Perry, Arie; Giannini, Caterina; Tihan, Tarik; Berger, Mitchel S; Wiemels, Joseph L; Bracci, Paige M; Eckel-Passow, Jeanette E; Lachance, Daniel H; Clarke, Jennifer; Taylor, Jennie W; Luks, Tracy; Wiencke, John K; Jenkins, Robert B; Wrensch, Margaret R

    2017-03-02

    The "integrated diagnosis" for infiltrating gliomas in the 2016 revised World Health Organization (WHO) classification of tumors of the central nervous system requires assessment of the tumor for IDH mutations and 1p/19q codeletion. Since TERT promoter mutations and ATRX alterations have been shown to be associated with prognosis, we analyzed whether these tumor markers provide additional prognostic information within each of the five WHO 2016 categories. We used data for 1206 patients from the UCSF Adult Glioma Study, the Mayo Clinic and The Cancer Genome Atlas (TCGA) with infiltrative glioma, grades II-IV for whom tumor status for IDH, 1p/19q codeletion, ATRX, and TERT had been determined. All cases were assigned to one of 5 groups following the WHO 2016 diagnostic criteria based on their morphologic features, and IDH and 1p/19q codeletion status. These groups are: (1) Oligodendroglioma, IDH-mutant and 1p/19q-codeleted; (2) Astrocytoma, IDH-mutant; (3) Glioblastoma, IDH-mutant; (4) Glioblastoma, IDH-wildtype; and (5) Astrocytoma, IDH-wildtype. Within each group, we used univariate and multivariate Cox proportional hazards models to assess associations of overall survival with patient age at diagnosis, grade, and ATRX alteration status and/or TERT promoter mutation status. Among Group 1 IDH-mutant 1p/19q-codeleted oligodendrogliomas, the TERT-WT group had significantly worse overall survival than the TERT-MUT group (HR: 2.72, 95% CI 1.05-7.04, p = 0.04). In both Group 2, IDH-mutant astrocytomas and Group 3, IDH-mutant glioblastomas, neither TERT mutations nor ATRX alterations were significantly associated with survival. Among Group 4, IDH-wildtype glioblastomas, ATRX alterations were associated with favorable outcomes (HR: 0.36, 95% CI 0.17-0.81, p = 0.01). Among Group 5, IDH-wildtype astrocytomas, the TERT-WT group had significantly better overall survival than the TERT-MUT group (HR: 0.48, 95% CI 0.27-0.87), p = 0.02). Thus, we present evidence that in

  14. True precocious puberty with vision loss

    PubMed Central

    Upreti, Vimal; Bhansali, Anil; Mukherjee, Kanchan K; Das, Sambit; Santosh, R; Dutta, Pinaki; Walia, Rama

    2009-01-01

    A 7-year-old boy presented with progressive vision loss and simultaneous development of precocious puberty. On evaluation he was found to have a solid cystic tumour in the sellar and suprasellar region. He underwent trans-sphenoidal resection of the tumour and histopathological examination revealed pilocytic astrocytoma. However, he later succumbed to postoperative sepsis. PMID:22140410

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

    PubMed

    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.

  16. A high throughput system for the evaluation of protein kinase C inhibitors based on Elk1 transcriptional activation in human astrocytoma cells.

    PubMed

    Sharif, T R; Sharif, M

    1999-02-01

    Protein kinase C (PKC) designates a family of kinases that regulate many essential functions including cell growth and differentiation. The tight regulation of PKC activity is crucial for maintaining normal cellular proliferation and excessive activity leads to abnormal or uncontrolled cell growth. Recent reports indicate that malignant glioma cell lines express 100 to 1000-fold higher PKC activity when compared to non-neoplastic astrocytes. This high activity correlates well with the proliferation of tumor cells in vitro. We recently reported on the anti-proliferative properties of selective PKC inhibitors on the growth of U-373MG human astrocytoma cell line, and their ability to block mitogen-activated protein (MAP) kinase pathway activated by substance P (SP) neuropeptide receptor signaling via a PKC-dependent mechanism. Therefore, inhibiting PKC activity by selective PKC inhibitors may present a promising approach for improving astroglial brain tumor therapy. For this purpose, we constructed a high throughput model cell system to evaluate the efficacy of PKC inhibitors. This system is based on the measurement of light production in U-373MG cells stably transfected with the luciferase reporter gene whose expression depends on the transcriptional activation of GAL4-Elk1 fusion protein by enzyme components of the MAP kinase pathway and the upstream activation of PKC (PKC activation-->MAP kinases-->GAL4-Elk1 phosphorylation-->luciferase expression-->luciferase activity). In brief, we have demonstrated that the PKC activator 12-O-tetradecanoyl phorbol 13-acetate (TPA)-induced luciferase activity in this cell system is mediated via the MAP kinase pathway and can be blocked in the presence of MEK1 selective inhibitors (PD 098059 or U0126). We also demonstrated that TPA-induced luciferase activity in U-373MG stable clones can be blocked by PKC inhibitors (CGP 41251, Go 6976, and GF 109203X) in a concentration dependent manner. In contrast, epidermal growth factor (EGF

  17. Neoadjuvant cisplatin plus temozolomide versus standard treatment in patients with unresectable glioblastoma or anaplastic astrocytoma: a differential effect of MGMT methylation.

    PubMed

    Capdevila, Laia; Cros, Sara; Ramirez, Jose-Luis; Sanz, Carolina; Carrato, Cristina; Romeo, Margarita; Etxaniz, Olatz; Hostalot, Cristina; Massuet, Ana; Cuadra, Jose Luis; Villà, Salvador; Balañà, Carmen

    2014-03-01

    Patients with unresectable glioblastoma or anaplastic astrocytoma have a dismal prognosis. The role of neoadjuvant chemotherapy prior to irradiation in these patients has been studied primarily in non-randomized studies. We have compared the effect of neoadjuvant chemotherapy plus radiotherapy versus concomitant radiotherapy plus temozolomide in a retrospective analysis of two consecutive series of patients in whom surgery consisted of biopsy only. From 2003 to 2005, 23 patients received two cycles of temozolomide plus cisplatin followed by radiotherapy (Cohort 1), and from 2006 to 2010, 23 additional patients received concomitant radiotherapy and temozolomide followed by adjuvant temozolomide (Cohort 2). In Cohort 1, 91.3 % of patients received all planned chemotherapy cycles. Progression-free and overall survival were 3.3 and 8.5 months, respectively. In Cohort 2, progression-free and overall survival were 5.1 and 11.2 months, respectively. No differences between the two groups were observed in rate of completion of radiotherapy, progression-free or overall survival. MGMT methylation was assessed in 91.3 % of patients. In Cohort 1, patients without MGMT methylation showed a trend towards shorter progression-free survival (P = 0.09), while in Cohort 2, patients without MGMT methylation had longer progression-free survival (P = 0.04). In the overall patient population, neoadjuvant temozolomide plus cisplatin had neither a positive nor negative influence on outcome. However, our findings indicate that patients with methylated MGMT may derive greater benefit from neoadjuvant temozolomide than those with unmethylated MGMT.

  18. D-1 dopaminergic and beta-adrenergic stimulation of adenylate cyclase in a clone derived from the human astrocytoma cell line G-CCM.

    PubMed

    Balmforth, A J; Ball, S G; Freshney, R I; Graham, D I; McNamee, H B; Vaughan, P F

    1986-09-01

    Clones have been isolated from the human astrocytoma cell line G-CCM. Homogenates of clone D384 contain an adenylate cyclase that is stimulated by 3,4-dihydroxyphenylethylamine (dopamine), noradrenaline, and isoprenaline with Ka apparent values of 4, 56, and 2.7 microM, respectively. The Ka apparent value for dopamine was increased by the D-1 antagonist cis-flupenthixol, 25 and 100 nM, to 23 and 190 microM, respectively, but was unaffected by propranolol (1 microM). Noradrenaline stimulation of adenylate cyclase was only partially inhibited by either propranolol (10 microM) or cis-flupenthixol (1 microM). Propranolol (10 microM), but not cis-flupenthixol (1 microM), prevented stimulation by isoprenaline. The stimulation of adenylate cyclase by dopamine and noradrenaline remained unchanged in the presence of phentolamine (1 microM) and sulpiride (1 microM). These results suggest that clone D384 contains both D-1 dopaminergic and beta-adrenergic receptors coupled to adenylate cyclase. Dopamine stimulates D384 adenylate cyclase through D-1 receptors, isoprenaline via beta-receptors, and noradrenaline through both receptors.

  19. The tachykinin peptide neurokinin B binds copper forming an unusual [CuII(NKB)2] complex and inhibits copper uptake into 1321N1 astrocytoma cells.

    PubMed

    Russino, Debora; McDonald, Elle; Hejazi, Leila; Hanson, Graeme R; Jones, Christopher E

    2013-10-16

    Neurokinin B (NKB) is a member of the tachykinin family of neuropeptides that have neuroinflammatory, neuroimmunological, and neuroprotective functions. In a neuroprotective role, tachykinins can help protect cells against the neurotoxic processes observed in Alzheimer's disease. A change in copper homeostasis is a clear feature of Alzheimer's disease, and the dysregulation may be a contributory factor in toxicity. Copper has recently been shown to interact with neurokinin A and neuropeptide γ and can lead to generation of reactive oxygen species and peptide degradation, which suggests that copper may have a place in tachykinin function and potentially misfunction. To explore this, we have utilized a range of spectroscopic techniques to show that NKB, but not substance P, can bind Cu(II) in an unusual [Cu(II)(NKB)2] neutral complex that utilizes two N-terminal amine and two imidazole nitrogen ligands (from each molecule of NKB) and the binding substantially alters the structure of the peptide. Using 1321N1 astrocytoma cells, we show that copper can enter the cells and subsequently open plasma membrane calcium channels but when bound to neurokinin B copper ion uptake is inhibited. This data suggests a novel role for neurokinin B in protecting cells against copper-induced calcium changes and implicates the peptide in synaptic copper homeostasis.

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

    PubMed

    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.

  1. Protein Kinase C-α–Mediated Regulation of Low-Density Lipoprotein Receptor–Related Protein and Urokinase Increases Astrocytoma Invasion

    PubMed Central

    Amos, Samson; Mut, Melike; diPierro, Charles G.; Carpenter, Joan E.; Xiao, Aizhen; Kohutek, Zachary A.; Redpath, Gerard T.; Zhao, Yunge; Wang, Jiahu; Shaffrey, Mark E.; Hussaini, Isa M.

    2008-01-01

    Aggressive and infiltrative invasion is one of the hallmarks of glioblastoma. Low-density lipoprotein receptor–related protein (LRP) is expressed by glioblastoma, but the role of this receptor in astrocytic tumor invasion remains poorly understood. We show that activation of protein kinase C-α (PKC-α) phosphorylated and down-regulated LRP expression. Pretreatment of tumor cells with PKC inhibitors, phosphoinositide 3-kinase (PI3K) inhibitor, PKC-α small interfering RNA (siRNA), and short hairpin RNA abrogated phorbol 12-myristate 13-acetate–induced down-regulation of LRP and inhibited astrocytic tumor invasion in vitro. In xenograft glioblastoma mouse model and in vitro transmembrane invasion assay, LRP-deficient cells, which secreted high levels of urokinase-type plasminogen activator (uPA), invaded extensively the surrounding normal brain tissue, whereas the LRP-overexpressing and uPA-deficient cells did not invade into the surrounding normal brain. siRNA, targeted against uPA in LRP-deficient clones, attenuated their invasive potential. Taken together, our results strongly suggest the involvement of PKC-α/PI3K signaling pathways in the regulation of LRP-mediated astrocytoma invasion. Thus, a strategy of combining small molecule inhibitors of PKC-α and PI3K could provide a new treatment paradigm for glioblastomas. PMID:17974965

  2. Expression pattern and sub-cellular distribution of phosphoinositide specific phospholipase C enzymes after treatment with U-73122 in rat astrocytoma cells.

    PubMed

    Lo Vasco, Vincenza Rita; Fabrizi, Cinzia; Panetta, Barbara; Fumagalli, Lorenzo; Cocco, Lucio

    2010-07-01

    Phosphoinositide specific phospholipase C (PI-PLC) enzymes interfere with the metabolism of inositol phospholipids (PI), molecules involved in signal transduction, a complex process depending on various components. Many evidences support the hypothesis that, in the glia, isoforms of PI-PLC family display different expression and/or sub cellular distribution under non-physiological conditions such as the rat astrocytes activation during neurodegeneration, the tumoural progression of some neoplasms and the inflammatory cascade activation after lipopolysaccharide administration, even if their role remains not completely elucidated. Treatment of a cultured established glioma cell line (C6 rat astrocytoma cell line) induces a modification in the pattern of expression and of sub cellular distribution of PI-PLCs compared to untreated cells. Special attention require PI-PLC beta3 and PI-PLC gamma2 isoforms, whose expression and sub cellular localization significantly differ after U-73122 treatment. The meaning of these modifications is unclear, also because the use of this N-aminosteroid compound remains controversial, inasmuch it has further actions which might contribute to the global effect recorded on the treated cells.

  3. A novel mutation in NF1 is associated with diverse intra-familial phenotypic variation and astrocytoma in a Chinese family.

    PubMed

    Banerjee, Santasree; Dai, Yi; Liang, Shengran; Chen, Huishuang; Wang, Yanyan; Tang, Lihui; Wu, Jing; Huang, Hui

    2016-09-01

    Neurofibromatosis type 1 (NF1) is a dysregulated neurocutaneous disorder, characterized by neurofibromas and café-au-lait spots. NF1 is caused by mutations in the NF1 gene, encoding neurofibromin. Here, we present a clinical molecular study of a three-generation Chinese family with NF1. The proband was a male patient who showed café-au-lait spots and multiple subcutaneous neurofibromas over the whole body, but his siblings only had regional lesions. The man's daughter presented with severe headache and vomiting. Neurological examination revealed an intracranial space occupying lesion. Surgery was undertaken and the histopathological examination showed a grade I-II astrocytoma. Next-Generation sequencing (Illumina HiSeq2500 Analyzers; Illumina, San Diego, CA, USA) and Sanger sequencing (ABI PRISM 3730 automated sequencer; Applied Biosystems, Foster City, CA, USA) identified the c.227delA mutation in the NF1 gene in the man. The mutation is co-segregated with the disease phenotypes among the affected members of this family and was absent in 100 healthy controls. This novel mutation results in a frameshift (p.Asn78IlefsX7) as well as truncation of neurofibromin by formation of a premature stop codon. Our results not only extended the mutational and phenotypic spectra of the gene and the disease, but also highlight the importance of the other genetic or environmental factors in the development and severity of the disease.

  4. MRI in treatment of adult gliomas.

    PubMed

    Henson, John W; Gaviani, Paola; Gonzalez, R Gilberto

    2005-03-01

    Diffuse astrocytomas of the adult cerebral hemispheres are unique among tumours in human beings in the extent to which their imaging features are related to histopathological characteristics and clinical behaviour. However, understanding is still restricted about the value of imaging features in the measurement of response and of progression in these tumours. The present approach used in clinical trials, which consists of an anatomical measurement of the enhancing tumour on MRI, has many problems, and might not be acceptable as a surrogate endpoint for survival in patients with glioblastoma who are enrolled in clinical trials. Dynamic imaging techniques, such as capillary permeability mapping, are being used in studies of new drugs that target specific molecular features of gliomas; however, the validity of these techniques has not been elucidated. Diffusion imaging can be valuable for fibre-tract mapping to assist surgical planning and might become useful in measuring early response to treatment in densely cellular tumours. Functional imaging techniques can be used to localise motor, sensory, and language-control areas before surgery. Intraoperative MRI has produced improvements in the extent of tumour resection, and molecular imaging is another technique on the horizon, which could come to have a role in clinical trials in the near future. Thus, as a rapidly expanding sphere of investigation, brain-tumour imaging is producing great excitement. The aim of these new techniques is to aid the identification of more effective treatments.

  5. Genetic alterations in uncommon low-grade neuroepithelial tumors: BRAF, FGFR1, and MYB mutations occur at high frequency and align with morphology.

    PubMed

    Qaddoumi, Ibrahim; Orisme, Wilda; Wen, Ji; Santiago, Teresa; Gupta, Kirti; Dalton, James D; Tang, Bo; Haupfear, Kelly; Punchihewa, Chandanamali; Easton, John; Mulder, Heather; Boggs, Kristy; Shao, Ying; Rusch, Michael; Becksfort, Jared; Gupta, Pankaj; Wang, Shuoguo; Lee, Ryan P; Brat, Daniel; Peter Collins, V; Dahiya, Sonika; George, David; Konomos, William; Kurian, Kathreena M; McFadden, Kathryn; Serafini, Luciano Neder; Nickols, Hilary; Perry, Arie; Shurtleff, Sheila; Gajjar, Amar; Boop, Fredrick A; Klimo, Paul D; Mardis, Elaine R; Wilson, Richard K; Baker, Suzanne J; Zhang, Jinghui; Wu, Gang; Downing, James R; Tatevossian, Ruth G; Ellison, David W

    2016-06-01

    Low-grade neuroepithelial tumors (LGNTs) are diverse CNS tumors presenting in children and young adults, often with a history of epilepsy. While the genetic profiles of common LGNTs, such as the pilocytic astrocytoma and 'adult-type' diffuse gliomas, are largely established, those of uncommon LGNTs remain to be defined. In this study, we have used massively parallel sequencing and various targeted molecular genetic approaches to study alterations in 91 LGNTs, mostly from children but including young adult patients. These tumors comprise dysembryoplastic neuroepithelial tumors (DNETs; n = 22), diffuse oligodendroglial tumors (d-OTs; n = 20), diffuse astrocytomas (DAs; n = 17), angiocentric gliomas (n = 15), and gangliogliomas (n = 17). Most LGNTs (84 %) analyzed by whole-genome sequencing (WGS) were characterized by a single driver genetic alteration. Alterations of FGFR1 occurred frequently in LGNTs composed of oligodendrocyte-like cells, being present in 82 % of DNETs and 40 % of d-OTs. In contrast, a MYB-QKI fusion characterized almost all angiocentric gliomas (87 %), and MYB fusion genes were the most common genetic alteration in DAs (41 %). A BRAF:p.V600E mutation was present in 35 % of gangliogliomas and 18 % of DAs. Pathogenic alterations in FGFR1/2/3, BRAF, or MYB/MYBL1 occurred in 78 % of the series. Adult-type d-OTs with an IDH1/2 mutation occurred in four adolescents, the youngest aged 15 years at biopsy. Despite a detailed analysis, novel genetic alterations were limited to two fusion genes, EWSR1-PATZ1 and SLMAP-NTRK2, both in gangliogliomas. Alterations in BRAF, FGFR1, or MYB account for most pathogenic alterations in LGNTs, including pilocytic astrocytomas, and alignment of these genetic alterations and cytologic features across LGNTs has diagnostic implications. Additionally, therapeutic options based upon targeting the effects of these alterations are already in clinical trials.

  6. Polymyositis - adult

    MedlinePlus

    ... rash is a sign of a similar condition, dermatomyositis . Common symptoms include: Muscle weakness in the shoulders ... in the treatment of refractory adult and juvenile dermatomyositis and adult polymyositis: a randomized, placebo-phase trial. ...

  7. Novel Proteins Regulated by mTOR in Subependymal Giant Cell Astrocytomas of Patients with Tuberous Sclerosis Complex and New Therapeutic Implications

    PubMed Central

    Tyburczy, Magdalena Ewa; Kotulska, Katarzyna; Pokarowski, Piotr; Mieczkowski, Jakub; Kucharska, Joanna; Grajkowska, Wieslawa; Roszkowski, Maciej; Jozwiak, Sergiusz; Kaminska, Bozena

    2010-01-01

    Subependymal giant cell astrocytomas (SEGAs) are rare brain tumors associated with tuberous sclerosis complex (TSC), a disease caused by mutations in TSC1 or TSC2, resulting in enhancement of mammalian target of rapamycin (mTOR) activity, dysregulation of cell growth, and tumorigenesis. Signaling via mTOR plays a role in multifaceted genomic responses, but its effectors in the brain are largely unknown. Therefore, gene expression profiling on four SEGAs was performed with Affymetrix Human Genome arrays. Of the genes differentially expressed in TSC, 11 were validated by real-time PCR on independent tumor samples and 3 SEGA-derived cultures. Expression of several proteins was confirmed by immunohistochemistry. The differentially-regulated proteins were mainly involved in tumorigenesis and nervous system development. ANXA1, GPNMB, LTF, RND3, S100A11, SFRP4, and NPTX1 genes were likely to be mTOR effector genes in SEGA, as their expression was modulated by an mTOR inhibitor, rapamycin, in SEGA-derived cells. Inhibition of mTOR signaling affected size of cultured SEGA cells but had no influence on their proliferation, morphology, or migration, whereas inhibition of both mTOR and extracellular signal-regulated kinase signaling pathways led to significant alterations of these processes. For the first time, we identified genes related to the occurrence of SEGA and regulated by mTOR and demonstrated an effective modulation of SEGA growth by pharmacological inhibition of both mTOR and extracellular signal-regulated kinase signaling pathways, which could represent a novel therapeutic approach. PMID:20133820

  8. Treatment of human astrocytoma U87 cells with silicon dioxide nanoparticles lowers their survival and alters their expression of mitochondrial and cell signaling proteins.

    PubMed

    Lai, James C K; Ananthakrishnan, Gayathri; Jandhyam, Sirisha; Dukhande, Vikas V; Bhushan, Alok; Gokhale, Mugdha; Daniels, Christopher K; Leung, Solomon W

    2010-10-05

    Recent evidence suggests silicon dioxide micro- and nanoparticles induce cytotoxic effects on lung cells. Thus, there is an increasing concern regarding their potential health hazard. Nevertheless, the putative toxicity of nanoparticles in mammalian cells has not yet been systematically investigated. We previously noted that several metallic oxide nanoparticles exert differential cytotoxic effects on human neural and nonneural cells. Therefore, we hypothesized that silicon dioxide nanoparticles induce cytotoxicity in U87 cells by lowering their survival by decreasing cell survival signaling and disturbing mitochondrial function. To investigate this hypothesis, we determined the activities of the key mitochondrial enzymes, citrate synthase and malate dehydrogenase, in astrocytoma U87 cells treated with silicon dioxide nanoparticles. In addition, we studied the expression of the mitochondrial DNA-encoded proteins, cytochrome C oxidase II and nicotinamide adenine dinucleotide (NADPH) dehydrogenase subunit 6, and cell signaling pathway protein extracellular signal-regulated kinase (ERK) and phosphorylated ERK in treated U87 cells. The activated form of ERK controls cell growth, differentiation, and proliferation. In parallel, we determined survival of U87 cells after treating them with various concentrations of silicon dioxide nanoparticles. Our results indicated that treatment with silicon dioxide nanoparticles induced decreases in U87 cell survival in a dose-related manner. The activities of citrate synthase and malate dehydrogenase in treated U87 cells were increased, possibly due to an energetic compensation in surviving cells. However, the expression of mitochondrial DNA-encoded cytochrome C oxidase subunit II and NADH dehydrogenase subunit 6 and the cell signaling protein ERK and phosphorylated ERK were altered in the treated U87 cells, suggesting that silicon dioxide nanoparticles induced disruption of mitochondrial DNA-encoded protein expression, leading to

  9. Up-regulation of NG2 proteoglycan and interferon-induced transmembrane proteins 1 and 3 in mouse astrocytoma: a membrane proteomics approach.

    PubMed

    Seyfried, Nicholas T; Huysentruyt, Leanne C; Atwood, James A; Xia, Qiangwei; Seyfried, Thomas N; Orlando, Ron

    2008-05-18

    Although brain tumors are classified as if their lineage were well understood, the relationship between the molecular events that specify neural cell lineage and brain tumors remains enigmatic. Traditionally, cell surface membrane antigens have served as biomarkers that distinguish brain tumor origin and malignancy. In this study, membrane proteins were identified from a terminally differentiated mouse astrocyte (AC) and CT-2A astrocytoma (CT-2A) cell line using liquid-chromatography coupled with tandem mass spectrometry (LC-MS/MS). A total of 321 and 297 protein groups with at least one unique peptide were identified in the AC and CT-2A cells. Using a label-free quantitative MS approach, 25 plasma membrane proteins in CT-2A were found significantly up- or down-regulated compared with those in AC. Three of the up-regulated proteins, chondroitin sulfate proteoglycan-4 (Cspg4), interferon-induced transmembrane protein-2 (IFITM2) and -3 (IFITM3) were further validated by semi-quantitative RT-PCR analysis. In addition, a third member of the IFITM family, interferon-induced transmembrane protein-1 (IFITM1) was also analyzed. Expression of Cspg4, IFITM1 and IFITM3 was significantly greater in the CT-2A cells than that in the AC cells. Interestingly, Cspg4, also known as neuronal/glial 2 (NG2) proteoglycan in human, is an oligodendrocyte progenitor marker. Therefore, our data suggest that the CT-2A tumor may be derived from NG2 glia rather than from fully differentiated astrocytes. Moreover, the CT-2A cells also express a series of interferon-induced signature proteins that may be specific to this tumor. These data highlight the utility of LC-MS/MS for the identification of brain tumor membrane biomarkers.

  10. Expression of cytokines by human astrocytomas following stimulation by C3a and C5a anaphylatoxins: specific increase in interleukin-6 mRNA expression.

    PubMed

    Sayah, S; Ischenko, A M; Zhakhov, A; Bonnard, A S; Fontaine, M

    1999-06-01

    C3a and C5a anaphylatoxins are two proinflammatory peptides generated during complement activation that act through distinct Gi protein-coupled receptors named C3aR and C5aR, respectively. We have demonstrated previously that human astrocytes expressed C3aR and C5aR constitutively and were able to produce a functional complement. In this study, we examined the effect of an anaphylatoxin stimulation on cytokine expression by human astrocyte cell lines. Interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha, and transforming growth factor-beta mRNA expression was studied by quantitative RT-PCR. Whereas IL-1beta, tumor necrosis factor-alpha, and transforming growth factor-beta mRNA levels remained unchanged, stimulation of astrocytoma cells (T98G, CB193, U118MG) by C3a, C5a, and peptidic C3aR and C5aR agonists induced an increase in the IL-6 mRNA level. The amount of IL-6 was markedly increased at 3 and 6 h and returned to the basal level at 9 h of stimulation. This response was specific, because pretreatment of cells with pertussis toxin or with polyclonal anti-C3aR or anti-C5aR antibodies completely blocked the IL-6 mRNA increase. The IL-6 response was also investigated at the protein level, but IL-6 protein was detected neither in cell lysates nor in supernatants of stimulated cells. The anaphylatoxin-mediated transcriptional activation of IL-6 gene suggests that C3a and C5a could play a role in priming glial cells during the inflammatory process in the brain.

  11. IDH mutations as an early and consistent marker in low-grade astrocytomas WHO grade II and their consecutive secondary high-grade gliomas.

    PubMed

    Juratli, Tareq A; Kirsch, Matthias; Robel, Katja; Soucek, Silke; Geiger, Kathrin; von Kummer, Rüdiger; Schackert, Gabriele; Krex, Dietmar

    2012-07-01

    This study investigated the prognostic and predictive significance of IDH1 and IDH2 mutations in low-grade astrocytomas (LGA). The presence and consistency of IDH mutations during the progression of LGA to secondary high-grade gliomas (sHGG) were detected. Samples of patients with LGA and sHGG were investigated. The genomic regions around IDH1 codon 132 and IDH2 codon 172 were PCR amplified and directly sequenced. Furthermore, the MGMT promoter status was provided using the methylation-specific PCR. Our population comprised 71 patients with a total of 45 pairs of LGA and their consecutive sHGG. Median follow-up was 9.6 years. IDH mutations were found in 36/45 LGA (80%) and their sHGG without changes in the mutation status. A total of 71 patients with LGA were analyzed according to clinical and molecular tumor-related factors: 56/71 patients (78.8%) had an IDH mutation without significant influence on the progression-free or overall survival (OS), and 22/71 (31%) of the patients received postoperative radiotherapy (RT) after diagnosis of LGA. Patients with early RT but without IDH mutations had the shortest survival. Our study shows that IDH mutation status is stable during the progression course of LGA to sHGG. The presence of IDH mutations fails to demonstrate a significant influence on survival in the multivariate analysis of LGA patients. Early RT appears to be beneficial only LGA patients with IDH-mutations.

  12. From the Cover: Vulnerability of C6 Astrocytoma Cells After Single-Compound and Joint Exposure to Type I and Type II Pyrethroid Insecticides.

    PubMed

    Romero, Delfina M; Berardino, Bruno G; Wolansky, Marcelo J; Kotler, Mónica L

    2017-01-01

    A primary mode-of-action of all pyrethroid insecticides (PYRs) is the disruption of the voltage-gated sodium channel electrophysiology in neurons of target pests and nontarget species. The neurological actions of PYRs on non-neuronal cells of the nervous system remain poorly investigated. In the present work, we used C6 astrocytoma cells to study PYR actions (0.1-50 μM) under the hypothesis that glial cells may be targeted by and vulnerable to PYRs. To this end, we characterized the effects of bifenthrin (BF), tefluthrin (TF), α-cypermethrin (α-CYP), and deltamethrin (DM) on the integrity of nuclear, mitochondrial, and lysosomal compartments. In general, 24- to 48-h exposures produced concentration-related impairment of cell viability. In single-compound, 24-h exposure experiments, effective concentration (EC)15s 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT assay) were computed as follows (in μM): BF, 16.1; TF, 37.3; α-CYP, 7.8; DM, 5.0. We found concentration-related damage in several C6-cell subcellular compartments (mitochondria, nuclei, and lysosomes) at ≥ 10(-1) μM levels. Last, we examined a mixture of all PYRs (ie, Σ individual EC15) using MTT assays and subcellular analyses. Our findings indicate that C6 cells are responsive to nM levels of PYRs, suggesting that astroglial susceptibility may contribute to the low-dose neurological effects caused by these insecticides. This research further suggests that C6 cells may provide relevant information as a screening platform for pesticide mixtures targeting nervous system cells by expected and unexpected toxicogenic pathways potentially contributing to clinical neurotoxicity.

  13. Knockdown of cytosolic 5'-nucleotidase II (cN-II) reveals that its activity is essential for survival in astrocytoma cells.

    PubMed

    Careddu, Maria Giovanna; Allegrini, Simone; Pesi, Rossana; Camici, Marcella; Garcia-Gil, Mercedes; Tozzi, Maria Grazia

    2008-08-01

    IMP preferring cytosolic 5'-nucleotidase (cN-II) is an ubiquitous nucleotide hydrolysing enzyme. The enzyme is widely distributed and its amino acid sequence is highly conserved among vertebrates. Fluctuations of cN-II activity have been associated with the pathogenesis of neurological disorders. The enzyme appears to be involved in the regulation of the intracellular availability of the purine precursor IMP and also of GMP and AMP, but the contribution of this activity and of its regulation to cell metabolism and to CNS cell functions remains uncertain. To address this issue, we used a vector based short hairpin RNA (shRNA) strategy to knockdown cN-II activity in human astrocytoma cells. Our results demonstrated that 53 h after transduction, cN-II mRNA was reduced to 17.9+/-0.03% of control cells. 19 h later enzyme activity was decreased from 0.7+/-0.026 mU/mg in control ADF cells to 0.45+/-0.046 mU/mg, while cell viability (evaluated by the MTT reduction assay) decreased up to 0.59+/-0.01 (fold vs control) and caspase 3 activity increased from 136+/-5.8 pmol min(-1) mg(-1) in control cells to 639+/-37.5 pmol min(-1) mg(-1) in silenced cells, thus demonstrating that cN-II is essential for cell survival. The decrease of enzyme activity causes apoptosis of the cultured cells without altering intracellular nucleotide and nucleoside concentration or energy charge. Since cN-II is highly expressed in tumour cells, our finding offers a new possible therapeutical approach especially against primary brain tumours such as glioblastoma, and to ameliorate chemotherapy against leukemia.

  14. (-)(125I)-iodopindolol, a new highly selective radioiodinated beta-adrenergic receptor antagonist: measurement of beta-receptors on intact rat astrocytoma cells

    SciTech Connect

    Barovsky, K.; Brooker, G.

    1980-01-01

    (-)-Pindolol, one of the most potent beta-adrenergic receptor antagonists, was radioiodinated using chloramine-T oxidation of carrier-free Na 125I and separated from unreacted pindolol to yield 2200 Ci/mmole (-)-(125I)-iodopindolol ((-)-(125I)-IPin). Mass and ultraviolet spectra confirmed that the iodination occurred on the indole ring, presumably at the 3 position. The binding of radiolabeled (-)-(125I)-IPin to beta-adrenergic receptors has been studied using intact C6 rat astrocytoma cells (2B subclone) grown in monolayer cultures. Binding of (-)(125IPin was saturable with time and concentration. Using 13 pM (-)-(125I)IPin, binding equilibrium was reached in 90 min at 21-22 degrees C. The reverse rate constant was 0.026 min-1 at 21/sup 0/C. Specific binding (expressed as 1 microM(-)-propranolol displaceable counts) of (-)-(125I)-IPin was 95% of total binding. Scatchard analysis of (-)-(125I)-I)Pin binding revealed approximately 4300 receptors/cell and a dissociation constant of 30 pM. This was in excellent agreement with the kinetically determined dissociation constant of 35 pM. Displacement by propranolol and isoproterenol showed that (-)-(125I)-IPin binding sites were pharmacologically and stereospecifically selective. These results indicate that (-)-(125I)-IPin, a pure (-)-stereoisomer, high specific activity radioligand, selectively binds to beta-adrenergic receptors in whole cells with a high percentage of specific binding and should therefore be useful in the study and measurement of cellular beta-adrenergic receptors.

  15. Coupling of the thrombin receptor to G12 may account for selective effects of thrombin on gene expression and DNA synthesis in 1321N1 astrocytoma cells.

    PubMed Central

    Post, G R; Collins, L R; Kennedy, E D; Moskowitz, S A; Aragay, A M; Goldstein, D; Brown, J H

    1996-01-01

    In 1321N1 astrocytoma cells, thrombin, but not carbachol, induces AP-1-mediated gene expression and DNA synthesis. To understand the divergent effects of these G protein-coupled receptor agonists on cellular responses, we examined Gq-dependent signaling events induced by thrombin receptor and muscarinic acetylcholine receptor stimulation. Thrombin and carbachol induce comparable changes in phosphoinositide and phosphatidylcholine hydrolysis, mobilization of intracellular Ca2+, diglyceride generation, and redistribution of protein kinase C; thus, activation of these Gq-signaling pathways appears to be insufficient for gene expression and mitogenesis. Thrombin increases Ras and mitogen-activated protein kinase activation to a greater extent than carbachol in 1321N1 cells. The effects of thrombin are not mediated through Gi, since ribosylation of Gi/Go proteins by pertussis toxin does not prevent thrombin-induced gene expression or thrombin-stimulated DNA synthesis. We recently reported that the pertussis toxin-insensitive G12 protein is required for thrombin-induced DNA synthesis. We demonstrate here, using transfection of receptors and G proteins in COS-7 cells, that G alpha 12 selectively couples the thrombin receptor to AP-1-mediated gene expression. This does not appear to result from increased mitogen-activated protein kinase activity but may reflect activation of a tyrosine kinase pathway. We suggest that preferential coupling of the thrombin receptor to G12 accounts for the selective ability of thrombin to stimulate Ras, mitogen-activated protein kinase, gene expression, and mitogenesis in 1321N1 cells. Images PMID:8930892

  16. Effect of docosahexaenoic acid and furan fatty acids on cytokinesis block micronucleus cytome assay biomarkers in astrocytoma cell lines under conditions of oxidative stress.

    PubMed

    Chua, Ann; Thomas, Philip; Wijesundera, Chakra; Clifton, Peter; Fenech, Michael

    2014-08-01

    Fatty acids from fish such as docosahexaenoic acid (DHA) are associated with improved brain function, whereas furan fatty acids (FFAs) also found in fish oil at low levels (1%) are thought to have antioxidant properties. Understanding their effects in astrocytes is important as these cells are responsible for maintaining healthy neurons via lipid homeostasis and distribution within the brain, and their decline with aging is a possible cause of dementia. We investigated the cytotoxic and genotoxic effects of DHA and FFA using the cytokinesis-block micronucleus cytome assay in in vitro cultures of U87MG (APOE ɛ3/ɛ3) and U118MG (APOE ɛ2/ɛ4) astrocytoma cell lines with and without a hydrogen peroxide (H2O2, 100 µM) challenge. U118MG was found to be more sensitive to the cytostatic, cytotoxic (i.e., apoptosis), and DNA damaging effects [micronuclei (MNi), nucleoplasmic bridges (NPBs), and nuclear buds (NBUDs)] of H2O2 (P < 0.01 and P < 0.001) when compared with U87MG. DHA at 100 µg/mL significantly affected cytostasis (P < 0.05) and increased DNA damage in the form of NPBs and MNi (P < 0.05) in both cell lines, whereas it decreased necrosis (P = 0.0251) in U87MG. Significant DHA-H2O2 interactions were observed for decreased necrosis (P = 0.0033) and DNA damage biomarkers (P < 0.0001) in the U87MG cell line and increased cytostasis (P < 0.0001) in the U118MG cell line. The effects of FFA also varied between the cell lines, with significant effects observed in decreased cytostasis (P = 0.0022) in the U87MG cell line, whereas increasing cytostasis (P = 0.0144) in the U118MG cell line. Overall, FFA exerted minimal effects on DNA damage biomarkers.

  17. CPR: Adult

    MedlinePlus

    Refresher Center Home FIRST AID, CPR and AED LIFEGUARDING Refresher Putting It All Together: CPR—Adult (2:03) Refresher videos only utilize this player QUICK LINKS Home RedCross.org Purchase Course ...

  18. 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

    SciTech Connect

    Teng, Chih-Chuan; Kuo, Hsing-Chun; Cheng, Ho-Chen; Wang, Ting-Chung; Sze, Chun-I

    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.

  19. Molecular genetics of adult grade II gliomas: towards a comprehensive tumor classification system.

    PubMed

    Figarella-Branger, Dominique; Bouvier, Corinne; de Paula, André Maues; Mokhtari, Karima; Colin, Carole; Loundou, Anderson; Chinot, Olivier; Metellus, Philippe

    2012-11-01

    Adult grade II low-grade gliomas (LGG) are classified according to the WHO as astrocytomas, oligodendrogliomas or mixed gliomas. TP53 mutations and 1p19q codeletion are the main molecular abnormalities recorded, respectively, in astrocytomas and oligodendrogliomas and in mixed gliomas. Although IDH mutations (IDH1 or IDH2) are recorded in up to 85 % of low-grade gliomas, IDH negative gliomas do occur. We have searched for p53 expression, 1p19q codeletion and IDH status (immunohistochemical detection of the common R132H IDH1 mutation and IDH direct sequencing). Internexin alpha (INA) expression previously recorded to be associated with 1p19q codeletion (1p19q+) gliomas was also analysed. Low-grade gliomas were accurately classified into four groups: group 1, IDH+/p53-/1p19q-; group 2, IDH+/p53-/1p19q+; group 3, IDH+/p53+/1p19q-; and group 4, triple negative gliomas. In contrast to the WHO classification, this molecular classification predicts overall survival on uni- and multivariate analysis (P = 0.001 and P = 0.007, respectively). Group 4 carries the worst prognosis and group 2 the best. Interestingly, p53 +/INA- expression predicts lack of 1p19q codeletion (specificity 100 %, VPP 100 %). The combined use of these three molecular markers allow for an accurate prediction of survival in LGG. These findings could significantly modify LGG classification and may represent a new tool to guide patient-tailored therapy. Moreover, immunohistochemical detection of p53, INA and mR132H IDH1 expression could represent an interesting prescreening test to be performed before 1p19q codeletion, IDH1 minor mutation and IDH2 mutation detection.

  20. Molecular interactions of ErbB1 (EGFR) and integrin-β1 in astrocytoma frozen sections predict clinical outcome and correlate with Akt-mediated in vitro radioresistance

    PubMed Central

    Petrás, Miklós; Lajtos, Tamás; Friedländer, Elza; Klekner, Álmos; Pintye, Éva; Feuerstein, Burt G.; Szöllősi, János; Vereb, György

    2013-01-01

    Introduction Treatment of astrocytoma is frequently hampered by radioresistance of the tumor. In addition to overexpression of ErbB1/EGFR, functional crosstalk between receptor tyrosine kinases and cell adhesion molecules may also contribute to therapy resistance. Methods Acceptor photobleaching FRET was implemented on frozen sections of clinical astrocytoma to check the role of ErbB1–integrin-β1 interaction. U251 glioma subclones were obtained by introducing extra CHR7 material or the ErbB1 gene to test the relevance and mechanism of this interaction in vitro. Results Grade IV tumors showed higher ErbB1 and integrin-β1 expression and greater ErbB1–integrin-β1 heteroassociation than did grade II tumors. Of these, the extent of molecular association was a single determinant of tumor grade and prognosis in stepwise logistic regression. In vitro, integrin-β1 was upregulated, and radiosensitivity was diminished by ectopic ErbB1 expression. Great excess of ErbB1 provided colony forming advantage over medium excess but did not yield better radiation resistance or faster proliferation and decreased to medium level over time, whereas integrin-β1 levels remained elevated and defined the extent of radioresistance. Increased expression of ErbB1 and integrin-β1 was paralleled by decreasing ErbB1 homoassociation and increasing ErbB1–integrin-β1 heteroassociation. Microscopic two-sided FRET revealed that pixels with higher ErbB1–integrin-β1 heteroassociation exhibited lowed ErbB1 homoassociation, indicating competition for association partners among these molecules. Boosted Akt phosphorylation response to EGF accompanied this shift toward heteroassociation, and the consequentially increased radioresistance could be reverted by inhibiting PI3K. Conclusion The clinically relevant ErbB1–integrin-β1 heteroassociation may be used as a target of both predictive diagnostics and molecular therapy. PMID:23595626

  1. Stereotactic Radiosurgery in Treating Patients With Brain Tumors

    ClinicalTrials.gov

    2012-03-21

    Adult Central Nervous System Germ Cell Tumor; Adult Malignant Meningioma; Adult Medulloblastoma; Adult Noninfiltrating Astrocytoma; Adult Oligodendroglioma; Adult Craniopharyngioma; Adult Meningioma; Brain Metastases; Adult Ependymoma; Adult Pineal Parenchymal Tumor; Adult Brain Stem Glioma; Adult Infiltrating Astrocytoma; Mixed Gliomas; Stage IV Peripheral Primitive Neuroectodermal Tumor

  2. Erlotinib in Treating Patients With Recurrent Malignant Glioma or Recurrent or Progressive Meningioma

    ClinicalTrials.gov

    2014-07-09

    Adult Anaplastic Astrocytoma; Adult Anaplastic Oligodendroglioma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade I Meningioma; Adult Grade II Meningioma; Adult Grade III Meningioma; Adult Mixed Glioma; Recurrent Adult Brain Tumor

  3. Adult Psychology.

    ERIC Educational Resources Information Center

    Bischof, Ledford J.

    This volume comprehensively reviews the research on the psychology of the middle aged (ages 40-65). Topics include the concept of maturity and maturation models, the measurement and influences of adult self image; marriage and sexual patterns; intergenerational relationships between and children; vocations and avocations (work, retirement, play,…

  4. Genetics of adult glioma.

    PubMed

    Goodenberger, McKinsey L; Jenkins, Robert B

    2012-12-01

    Gliomas make up approximately 30% of all brain and central nervous system tumors and 80% of all malignant brain tumors. Despite the frequency of gliomas, the etiology of these tumors remains largely unknown. Diffuse gliomas, including astrocytomas and oligodendrogliomas, belong to a single pathologic class but have very different histologies and molecular etiologies. Recent genomic studies have identified separate molecular subtypes within the glioma classification that appear to correlate with biological etiology, prognosis, and response to therapy. The discovery of these subtypes suggests that molecular genetic tests are and will be useful, beyond classical histology, for the clinical classification of gliomas. While a familial susceptibility to glioma has been identified, only a small percentage of gliomas are thought to be due to single-gene hereditary cancer syndromes. Through the use of linkage studies and genome-wide association studies, multiple germline variants have been identified that are beginning to define the genetic susceptibility to glioma.

  5. ADULT EDUCATION OF MIGRANT ADULTS.

    ERIC Educational Resources Information Center

    BEAL, CATHERINE; AND OTHERS

    UNITS ON MIGRANT ADULT EDUCATION, AND A UNIT ON ORGANIZING INFORMAL GROUPS OF MIGRANT WOMEN TO DISCUSS MAINTAINING AND IMPROVING THEIR TEMPORARY HOMES, ARE PRESENTED. THE GOALS OF THE UNIT ON EDUCATION FOR MIGRANT MEN ARE ECONOMIC INDEPENDENCE, BETTER HEALTH AND WELL-BEING, AND BETTER HANDLING OF RESPONSIBILITIES. THE MAIN DIVISIONS OF THE…

  6. Panic Disorder among Adults

    MedlinePlus

    ... Autism Spectrum Disorder (ASD) Eating Disorders Among Adults - Anorexia Nervosa Eating Disorders Among Adults - Binge Eating Disorder ... Autism Spectrum Disorder (ASD) Eating Disorders Among Adults - Anorexia Nervosa Eating Disorders Among Adults - Binge Eating Disorder ...

  7. Obstructive sleep apnea - adults

    MedlinePlus

    Sleep apnea - obstructive - adults; Apnea - obstructive sleep apnea syndrome - adults; Sleep-disordered breathing - adults; OSA - adults ... When you sleep, all of the muscles in your body become more relaxed. This includes the muscles that help keep your ...

  8. Biomarkers in the Detection of Prostate Cancer in African Americans

    DTIC Science & Technology

    2014-09-01

    carcinoma 10 choroid plexus carcinoma 8 lymphoma 10 neuroblastoma 8 benign neural tumor 10 colon-non neoplastic 8 dysgerminoma 10 lipoma 8...ganglioglioneuroma 10 hepatoblastoma 8 pilocytic astrocytoma 10 neuroblastoma 8 PNET 10 cellular fi broadenoma breast 8 embryonal rhabdomyosarcoma 10... neuroblastoma 8 ganglioglioneuroma 10 skull mass 8 spleen, normal 10 myxoid neoplasm-malignant 8 endodermal sinus tumor 10 Langerhans histiocytosis 8 pancreatic

  9. Bafetinib in Treating Patients With Recurrent High-Grade Glioma or Brain Metastases

    ClinicalTrials.gov

    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

  10. 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

    ClinicalTrials.gov

    2015-03-02

    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

  11. Adult Development and Learning of Older Adults

    ERIC Educational Resources Information Center

    Roberson, Donald N., Jr.

    2005-01-01

    This summary of adult development covers a wide range of authors. Adult development is one way of understanding how the internal and external changes in our lives have an impact on learning. Of particular importance in this work are the developmental issues of older adults. I present various theories of adult development such as linear and…

  12. Preparing Educators of Adults.

    ERIC Educational Resources Information Center

    Grabowski, Stanley M.; And Others

    Model programs are described for two areas of adult education--the preparation of adult educators and the training conducted by adult educators. In Chapter One, Phyllis Caldwell reviews the literature concerning the preservice training of adult educators, concentrating on the competencies of adult education administrators and teachers. In Chapter…

  13. Adults Need Vaccines, Too!

    MedlinePlus

    ... turn JavaScript on. Feature: Adult Vaccinations Adults Need Vaccines, Too! Past Issues / Summer 2015 Table of Contents ... of the millions of adults not receiving the vaccines you need? What vaccines do you need? All ...

  14. Brain tumor - primary - adults

    MedlinePlus

    ... Vestibular schwannoma (acoustic neuroma) - adults; Meningioma - adults; Cancer - brain tumor (adults) ... Primary brain tumors include any tumor that starts in the brain. Primary brain tumors can start from brain cells, ...

  15. Adult Day Care

    MedlinePlus

    ... Page Resize Text Printer Friendly Online Chat Adult Day Care Adult Day Care Centers are designed to provide care and ... adults who need assistance or supervision during the day. Programs offer relief to family members and caregivers, ...

  16. Adult Still's disease

    MedlinePlus

    Still's disease - adult; AOSD ... than 1 out of 100,000 people develop adult-onset Still's disease each year. It affects women more often than men. The cause of adult Still's disease is unknown. No risk factors for ...

  17. Adult Recruitment Practices.

    ERIC Educational Resources Information Center

    Kaufman, Juliet, Ed.; And Others

    Findings of an American College Testing Program 1981 survey on college recruitment of adult students are summarized, and 12 articles on adult recruitment are presented. Titles and authors are as follows: "Adult Recruitment Practices: A Report of a National Survey" (Patricia Spratt, Juliet Kaufmann, Lee Noel); "Three Programs for Adults in Shopping…

  18. Amyloid-β(25-35) induces a permanent phosphorylation of HSF-1, but a transitory and inflammation-independent overexpression of Hsp-70 in C6 astrocytoma cells.

    PubMed

    Calvillo, Minerva; Diaz, Alfonso; Limon, Daniel I; Mayoral, Miguel Angel; Chánez-Cárdenas, María Elena; Zenteno, Edgar; Montaño, Luis F; Guevara, Jorge; Espinosa, Blanca

    2013-10-01

    Two hallmarks of Alzheimer diseases are the continuous inflammatory process, and the brain deposit of Amyloid b (Aβ), a cytotoxic protein. The intracellular accumulation of Aβ(25-35) fractions, in the absence of Heat Shock proteins (Hsṕs), could be responsible for its cytotoxic activity. As, pro-inflammatory mediators and nitric oxide control the expression of Hsṕs, our aim was to investigate the effect of Aβ(25-35) on the concentration of IL-1β, TNF-α and nitrite levels, and their relation to pHSF-1, Hsp-60, -70 and -90 expressions, in the rat C6 astrocyte cells. Interleukin-specific ELISA kits, immunohistochemistry with monoclonal anti-Hsp and anti pHSF-1 antibodies, and histochemistry techniques, were used. Our results showed that Aβ25-35 treatment of C6 cells increased, significantly and consistently the concentration of IL-1β, TNF-α and nitrite 3 days after initiating treatment. The immunoreactivity of C6 cells to Hsp-70 reached its peak after 3 days of treatment followed by an abrupt decrease, as opposed to Hsp-60 and -90 expressions that showed an initial and progressive increase after 3 days of Aβ(25-35) treatment. pHSF-1 was identified throughout the experimental period. Nevertheless, progressive and sustained cell death was observed during all the treatment times and it was not caspase-3 dependent. Our results suggest that Hsp-70 temporary expression serves as a trigger to inhibit casapase-3 pathway and allow the expression of Hsp-60 and -90 in C6 astrocytoma cells stimulated with Aβ(25-35).

  19. Glioblastoma Multiforme and Adult Neurogenesis in the Ventricular-Subventricular Zone: A Review.

    PubMed

    Capdevila, Claudia; Rodríguez Vázquez, Lucía; Martí, Joaquín

    2017-07-01

    Brain cancers account for <1,5% of all new cancer cases reported in the United States each year. Due to their invasive and heterogeneous nature, in addition to their resistance to multimodal treatments, these tumors are usually fatal. Gliomas, and in particular high-grade astrocytomas such as glioblastoma multiforme (GBM), are the most common and lethal primary tumors of the central nervous system. The median survival of most patients is less than 1 year after application of multimodal therapies. The question is why are these cancers so injurious? And above all, how is it possible for a so carefully orchestrated area like the brain to develop such tumors? This brings us to the study of glioma stem cells, their specialized niches (perivascular and hypoxic), and the neurogenic phenomena that takes place within the adult ventricular-subventricular zone: a structure that lies at the intersection between brain development and gliomagenesis. J. Cell. Physiol. 232: 1596-1601, 2017. © 2016 Wiley Periodicals, Inc.

  20. Phase II Evaluation of Gefitinib in Patients With Newly Diagnosed Grade 4 Astrocytoma: Mayo/North Central Cancer Treatment Group Study N0074

    SciTech Connect

    Uhm, Joon H.; Ballman, Karla V.; Wu Wenting; Giannini, Caterina; Krauss, J.C.; Buckner, Jan C.; James, C.D.; Scheithauer, Bernd W.; Behrens, Robert J.; Flynn, Patrick J.; Schaefer, Paul L.; Dakhill, Shaker R.; Jaeckle, Kurt A.

    2011-06-01

    Purpose: Amplification of the epidermal growth factor receptor (EGFR) gene represents one of the most frequent gene alterations in glioblastoma (GBM). In the current study, we evaluated gefitinib, a potent EGFR inhibitor, in the treatment of adults with newly diagnosed GBM. Methods and Materials: Ninety-eight patients (96 evaluable) were accrued between May 18, 2001, and August 2, 2002. All were newly diagnosed GBM patients who were clinically and radiographically stable/improved after radiation treatment (enrollment within 5 weeks of radiation completion). No prior chemotherapy was permitted. EGFR amplification/mutation, as assessed by fluorescence in situ hybridization and immunohistochemistry, was not required for treatment with gefitinib but was studied when tissues were available. Gefitinib was administered at 500 mg each day; for patients receiving dexamethasone or enzyme-inducing (CYP3A4) agents, dose was escalated to a maximum of 1,000 mg QD. Treatment cycles were repeated at 4-week intervals with brain magnetic resonance imaging at 8-week intervals. Results: Overall survival (OS; calculated from time of initial surgery) at 1 year (primary end point) with gefitinib was 54.2%, which was not statistically different compared with that of historical control population (48.9%, data from three previous Phase III North Central Cancer Treatment Group studies of newly diagnosed GBM patients). Progression-free survival (PFS) at 1 year post-RT (16.7%) was also not significantly different to that of historical controls (30.3%). Clinical outcome was not affected by EGFR status (amplification or vIII mutation). Fatigue (41%), rash (62%), and loose stools (58%) constituted the most frequent adverse events, the majority of these being limited to Grade 1/2. Of note, the occurrence of drug-related adverse effects, such as loose stools was associated with improved OS. Conclusions: In our evaluation of nearly 100 patients with newly diagnosed GBM, treatment with adjuvant

  1. Clueless? Adult Mysteries with Young Adult Appeal.

    ERIC Educational Resources Information Center

    Charles, John; Morrison, Joanna

    1997-01-01

    Presents a list of adult mystery titles for young adult readers. Includes first titles in a series (for reading in order); new and lesser-known mystery authors' works are the focus. Annotations include plot summary. The rest of each annotation is for professional use (includes date and name of award bestowed). (AEF)

  2. Young Adult Literature for Young Adult Males.

    ERIC Educational Resources Information Center

    Gill, Sam D.

    1999-01-01

    Argues that young adult literature can play a significant role in the emotional and mental health of an adolescent as well as help young males become more literate. Offers a 19-item annotated list of young adult novels with male protagonists, sorted by themes: nature and adventure stories, sports stories, genre stories, historical stories, and…

  3. Erlotinib in Treating Patients With Solid Tumors and Liver or Kidney Dysfunction

    ClinicalTrials.gov

    2013-01-15

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Pilocytic Astrocytoma; Adult Primary Hepatocellular Carcinoma; Adult Subependymoma; Advanced Adult Primary Liver Cancer; Advanced Malignant Mesothelioma; Male Breast Cancer; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Adult Brain Tumor; Recurrent Adult Primary Liver Cancer; Recurrent Anal Cancer; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Bladder Cancer; Recurrent Breast Cancer; Recurrent Cervical Cancer; Recurrent Colon Cancer; Recurrent Esophageal Cancer; Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Recurrent Lymphoepithelioma of the Nasopharynx; Recurrent Lymphoepithelioma of the Oropharynx; Recurrent Malignant Mesothelioma; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Pancreatic Cancer; Recurrent Prostate Cancer; Recurrent Rectal Cancer; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage II Esophageal Cancer; Stage II Pancreatic Cancer; Stage III Esophageal Cancer

  4. Depression in Older Adults

    ERIC Educational Resources Information Center

    Stickle, Fred; Onedera, Jill D.

    2006-01-01

    The purpose of this article is to address selected aspects of depression in older adults. Specifically, symptoms, risk factors, diagnosis, and interventions for depression in older adults are reviewed.

  5. Immunization Schedules for Adults

    MedlinePlus

    ... ACIP Vaccination Recommendations Why Immunize? Vaccines: The Basics Immunization Schedules for Adults in Easy-to-read Formats ... previous immunizations. View or Print a Schedule Recommended Immunizations for Adults (19 Years and Older) by Age ...

  6. Adult Education Update

    ERIC Educational Resources Information Center

    Hall, Clyde W.

    1975-01-01

    Summarized are speeches dealing with adult education's stiff-necked adherence to middle-class values; the need for upgraded management skills; and a report of a study of adult education in area vocational schools in Georgia. (Author/AJ)

  7. O8.04TEMOZOLOMIDE AFTER RADIOTHERAPY IN RECURRENT “LOW-GRADE” DIFFUSE BRAINSTEM GLIOMA IN ADULTS

    PubMed Central

    Reyes-Botero, G.; Laigle-Donadey, F.; Mokhtari, K.; Martin-Duverneuil, N.; Delattre, J.Y.

    2014-01-01

    INTRODUCTION: Diffuse brainstem glioma is a rare disease in adults. Radiotherapy (RT) is frequently used as initial treatment. However, only limited data is available concerning chemotherapy efficacy at relapse after RT. Temozolomide (TMZ) is frequently used in progressive supratentorial gliomas after RT, but its efficacy in diffuse brainstem gliomas in adults has not been reported. PATIENTS AND METHODS: We conducted a retrospective analysis including patients from our database with non-enhancing diffuse brainstem glioma (histological or MRI criteria compatible with low-grade glioma) who received TMZ at relapse after RT. Tumors localized in the pons, medulla oblongata or midbrain were analyzed excluding supratentorial or infratentorial tumors secondary infiltrating the brainstem. Clinical and radiological responses were assessed and progression-free survival (PFS) and overall survival (OS) time were estimated. RESULTS: In total, 15 adult patients (median age 34 years) were selected. Histological analysis was available in 5 cases showing grade II oligodendroglioma (2 cases), grade II oligoastrocytoma (2 cases), grade II astrocytoma (1 case). Ten patients were selected by MRI criteria only. All patients received RT as initial treatment obtaining a median PFS of 34.2 months (95% CI 24.1-44.2). Median KPS at the time of relapse after RT was 80. TMZ was administered orally at 150-200mg/m2 for 5 days every 28 days at progression disease after RT. Clinical improvement after TMZ was observed in 9 cases (60%) whereas radiological assessment detected 6 partial responses. Estimated median PFS after TMZ was 9.5 months (95% CI 7.9-11) and median OS was 14.4 months (95% CI 10.5-18.2). Grade 3 thrombocytopenia was observed in 26% of cases. CONCLUSIONS: TMZ could be useful in adult patients with progressive diffuse low-grade brainstem glioma after RT failure. Further studies are warranted to detect clinical and biological markers of response to TMZ.

  8. Adult Education in Sweden.

    ERIC Educational Resources Information Center

    Miller, Harry; And Others

    Folk high schools, study circles, labor market training, union education, and municipal adult schools are the major providers of adult education in Sweden. For the most part, these programs are financed by the government and are tuition free. Folk high schools, which are the oldest type, were founded to provide young adults with a general civic…

  9. The Adult Experience.

    ERIC Educational Resources Information Center

    Belsky, Janet

    The 14 chapters of this textbook chronicle adult development from youth through old age, emphasizing both research and interviews with adults at various stages in their lives. Topics covered include the following: (1) the academic field of adult development; (2) theories and research methods; (3) aging and disease prevention; (4) sexuality and…

  10. Adult Survival Skills Assessment.

    ERIC Educational Resources Information Center

    Walsko, Gregory M.

    The purpose of this instrument is to supplement data from the Adult Basic Learning Examination in assessing the functional level of adults in daily situations. It may also be used as a teaching tool for adults requesting tutoring in specific concepts and skills presented in the instrument. This instrument is an informal assessment instrument and…

  11. Kids Who Outwit Adults.

    ERIC Educational Resources Information Center

    Seita, John R.; Brendtro, Larry K.

    Kids who distrust adults are highly skilled at hiding their real nature and resisting change. Most adults shun such youths or get mired in conflict with them. Punitive get tough practices as well as traditional flaw-fixing treatment are reactive strategies that often drive these youths further from adult bonds and reinforce oppositional and…

  12. Urbanization and Adult Education

    ERIC Educational Resources Information Center

    Short, W. Fisher

    1974-01-01

    The impact of urbanization, the main tasks facing the adult educator in an urban context, identifying the casualties of urbanization, recognizing and dealing with social deprivation, and the various agencies involved in adult education are relevant considerations for adult educators. (MW)

  13. Dimensions of Adult Learning

    ERIC Educational Resources Information Center

    Foley, Griff, Ed.

    2004-01-01

    This broad introduction to adult and postcompulsory education offers an overview of the field for students, adult educators and workplace trainers. The book establishes an analytical framework to emphasize the nature of learning and agency of learners; examines the core knowledge and skills that adult educators need; discusses policy, research and…

  14. Adult Learning: A Reader.

    ERIC Educational Resources Information Center

    Sutherland, Peter, Ed.

    This book on adult learning is divided into six sections. Section 1, Cognitive Processes, includes the following chapters: "Cognitive Processes: Contemporary Paradigms of Learning" (Jack Mezirow); "Information Processing, Memory, Age and Adult Learning" (Gillian Boulton-Lewis); "Adult Learners' Metacognitive Behaviour in Higher Education" (Barry…

  15. Adult Education in Israel.

    ERIC Educational Resources Information Center

    Kirmayer, Paul, Ed.; And Others

    This volume contains 13 articles that reflect the development of adult education in Israel during recent years. The material relates to the principal areas with which the Division of Adult Education deals: formal and nonformal education for adults, language and cultural absorption of new immigrants, and training of facilitators for parental…

  16. Adults Role in Bullying

    ERIC Educational Resources Information Center

    Notar, Charles E.; Padgett, Sharon

    2013-01-01

    Do adults play a role in bullying? Do parents, teachers, school staff, and community adult leaders influence bullying behavior in children and teenagers? This article will focus on research regarding all adults who have almost daily contact with children and teens and their part in how bullying is identified, addressed, and prevented. This article…

  17. Adult Education in Greece

    ERIC Educational Resources Information Center

    Kokkos, Alexios

    2008-01-01

    The central aim of this article is to analyse the current situation of adult education in Greece. The article focuses on the following points: (a) the degree of participation in programmes of continuing professional training and general adult education courses, (b) the quality and the outcomes of the adult education provision in Greece, and (c)…

  18. Adult Competency Education Profile.

    ERIC Educational Resources Information Center

    Bureau of Occupational and Adult Education (DHEW/OE), Washington, DC. Div. of Adult Education.

    A compilation of abstracts of 120 current Adult Performance Level (APL) and Adult Competency Education (ACE) federally supported projects being conducted in 34 States and the District of Columbia, this project profile was developed for adult and secondary education administrators, teachers, and program developers who are beginning or are currently…

  19. Adult Competency Education Resources.

    ERIC Educational Resources Information Center

    Bureau of Occupational and Adult Education (DHEW/OE), Washington, DC. Div. of Adult Education.

    A compilation of brief descriptions of 20 current resources for Adult Performance Level (APL) and Adult Competency Education (ACE) programs, this guide was developed for adult and secondary education administrators, teachers, and program developers who are beginning or are already involved with APL/ACE programs. Each citation contains information…

  20. Adult Academy Volunteer Manual.

    ERIC Educational Resources Information Center

    Cora, Marie T., Ed.; Wood, Nicole R., Ed.

    This handbook was written specifically for volunteer tutors but is appropriate for teachers, student interns, coordinators, and others working with Adult Basic Education (ABE) and English-as-a-Second-Language (ESL) adult learners. It presents an overview of adult and non-traditional education models, some principles of reading and writing, a…

  1. Canadian Adult Basic Education.

    ERIC Educational Resources Information Center

    Brooke, W. Michael, Comp.

    "Trends," a publication of the Canadian Association for Adult Education, is a collection of abstracts on selected subjects affecting adult education; this issue is on adult basic education (ABE). It covers teachers and teacher training, psychological factors relating to the ABE teacher and students, manuals for teachers, instructional…

  2. Young Adult Services Manual.

    ERIC Educational Resources Information Center

    Boegen, Anne, Ed.

    Designed to offer guidelines, ideas and help to those who provide library service to young adults, this manual includes information about the provision of young adult (YA) services in six sections. The first section, which addresses planning and administration, includes a definition of a young adult and a checklist for determining community needs…

  3. Adult Educators' Core Competences

    ERIC Educational Resources Information Center

    Wahlgren, Bjarne

    2016-01-01

    Which competences do professional adult educators need? This research note discusses the topic from a comparative perspective, finding that adult educators' required competences are wide-ranging, heterogeneous and complex. They are subject to context in terms of national and cultural environment as well as the kind of adult education concerned…

  4. An Adult ESL Curriculum.

    ERIC Educational Resources Information Center

    South Carolina Literacy Resource Center, Columbia.

    This curriculum framework for adult literacy was written by 21 South Carolina adult English-as-a-Second-Language (ESL) instructors, as submitted to the South Carolina Literacy Resource Center. It is based on current theories in the fields of adult education and second language acquisition and is designed to be flexible so that it may be adapted to…

  5. 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.

    PubMed

    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

  6. Obsessive Compulsive Disorder among Adults

    MedlinePlus

    ... Autism Spectrum Disorder (ASD) Eating Disorders Among Adults - Anorexia Nervosa Eating Disorders Among Adults - Binge Eating Disorder ... Autism Spectrum Disorder (ASD) Eating Disorders Among Adults - Anorexia Nervosa Eating Disorders Among Adults - Binge Eating Disorder ...

  7. Intraoperative Radiotherapy in Childhood Malignant Astrocytoma

    PubMed Central

    Rana, Sohail R.; Haddy, Theresa B.; Ashayeri, Ebrahim; Goldson, Alfred L.

    1984-01-01

    A 12-year-old black male patient with glioblastoma multiforme was treated with intraoperative radiotherapy followed by conventional external beam radiation and chemotherapy. The authors' clinical experience with these therapeutic measures is discussed. PMID:6330375

  8. Adult Education Regional Planning

    ERIC Educational Resources Information Center

    California Community Colleges, Chancellor's Office, 2015

    2015-01-01

    For more than one hundred and fifty years, until 2008, California was an undisputed national leader in its commitment to adult education. The state's investment in adult learners topped $750 million, a sum greater than the combined total of every other state in the nation. However, for the past several years recession and fiscal crisis have left…

  9. Young Adult Library Services.

    ERIC Educational Resources Information Center

    The Bookmark, 1985

    1985-01-01

    Eight articles in this Spring 1985 issue of The Bookmark focus on young adult library services. In addition to these thematic articles, an introduction and three reports are presented. The issue contains: (1) "In Perspective" (E. J. Josey); (2) "Young Adult Literature in the 1980's--Awesome!" (Ellin Chu); (3) "Young Adult…

  10. Toward Transpersonal Adult Development

    ERIC Educational Resources Information Center

    Boucouvalas, Marcie

    2016-01-01

    As a foundation for discussing transpersonal adult development, the author traces her trajectory, involvement in, and contribution to the modern transpersonal movement and her introduction of it to the adult learning literature, beginning during the early 1980s. Highlighted are the transpersonal domain and a differentiation between transpersonal…

  11. Adult Day Services

    MedlinePlus

    A Smart Choice Adult Day Services Comparison At-a-Glance 1 Adult Day Services Assisted Living Home Care Nursing Homes Live at home with family ... supervision Nursing care available as needed during the day Flexibility to receive care only on days when ...

  12. Adult Tech Prep.

    ERIC Educational Resources Information Center

    Schaad, Donna

    For over 2 years, Blak Hawk College (Illinois) has provided high school equivalency (GED) candidates and recipients, older returning students, and underprepared high school graduates with a Tech Prep curriculum to give them the skills to make the transition from adult basic education to college or work. The Adult Tech Prep (ATP) core curriculum…

  13. Authenticity in Adult Learning

    ERIC Educational Resources Information Center

    Ashton, Sam

    2010-01-01

    This paper is concerned with the relationship between authenticity and adult learning and prompted by some studies in which adult "authentic learning" is a central concept. The implication revealed by them is that real-worldness of learning contexts, learning content and learning tasks is perceived as conferring authenticity on learning. Here,…

  14. Adult Learning and Education

    ERIC Educational Resources Information Center

    Rubenson, Kjell, Ed.

    2011-01-01

    As individuals and societies try to respond to fundamental economic and social transformation, the field of adult learning and education is rapidly getting increased attention and new topics for research on adult learning have emerged. This collection of articles from the International Encyclopedia of Education 3e offers practitioners and…

  15. Today's Adult Students

    ERIC Educational Resources Information Center

    Reese, Susan

    2012-01-01

    Who are the adult students in career and technical education (CTE) today? There is not one simple answer to that question. Some are young with little life experience, while others are returning to the workforce and learning new skills to reinvent themselves. Whatever the case, educating adult students is an integral part of ACTE's mission, and the…

  16. Adult Literacy in Zanzibar.

    ERIC Educational Resources Information Center

    Saadat, Ahmed H.

    The philosophy behind adult literacy in Zanzibar is that adult literacy is a process whereby the illiterate is empowered to become aware of his or her potential. Literacy activities emphasize a relation to work, sometimes known as functional literacy. Specific objectives of literacy programs are to improve living conditions, impart self-reliant…

  17. Adult Vocational Trajectory.

    ERIC Educational Resources Information Center

    Riverin-Simard, Danielle

    1990-01-01

    Proposes a "spatial-temporal" model conceiving adult vocational development as a complex and constant readjustment in always changing perception of personal space-time, based on interviews of 786 adults. Presents two propositions of this model: the continuous alternation between states of instability and interaction of influences.…

  18. Counseling Adult Adoptees

    ERIC Educational Resources Information Center

    Corder, Kate

    2012-01-01

    This review presents various resources about working with adult adoptees in order to inform counselors in their practice. Topics covered include basics of adoption, including types of adoption and adoption statistics; possible issues adult adoptees may face; and suggestions and implications for counselors. The article addresses some of the serious…

  19. Alternative Programming for Adults.

    ERIC Educational Resources Information Center

    Flint, Thomas A.; Frey, Ruth

    2003-01-01

    The Council for Adult and Experiential Learning is currently cataloguing alternative programming features that are most effective with adult students in a best practices inventory organized around a framework of high-level descriptive principles of effectiveness. This chapter identifies a few interesting features from a quick survey of this…

  20. Adult Education and Development.

    ERIC Educational Resources Information Center

    Hinzen, Heribert, Ed.

    2002-01-01

    This document contains 19 papers on adult education and development worldwide. The following papers are included: "Editorial" (Heribert Hinzen); "Lifelong Learning in Europe: Moving towards EFA (Dakar Framework for Action on Education for All) Goals and the CONFINTEA V Agenda" (Sofia Conference on Adult Education);…

  1. Adult Education in Finland

    ERIC Educational Resources Information Center

    Szekely, Radu

    2006-01-01

    Ever since the first ideas of national independence appeared in Finland, adult education has played an essential role in shaping the destiny of the Finns. With a history of almost 130 years, during which it has continuously increased in quality and quantity, the Finnish adult education system has ensured that Finland stays among the most…

  2. Financing of Adult Education

    ERIC Educational Resources Information Center

    Archer, David

    2007-01-01

    The 2008 EFA Global Monitoring Report recognises adult literacy as the most neglected of the EFA goals. It is neglected most obviously in respect of the financial allocations made by governments and donors. This shortage of financing creates a dangerous situation in which adult educators seek to convince politicians to invest, based on false…

  3. Gender Dysphoria in Adults.

    PubMed

    Zucker, Kenneth J; Lawrence, Anne A; Kreukels, Baudewijntje P C

    2016-01-01

    Gender dysphoria (GD), a term that denotes persistent discomfort with one's biologic sex or assigned gender, replaced the diagnosis of gender identity disorder in the Diagnostic and Statistical Manual of Mental Disorders in 2013. Subtypes of GD in adults, defined by sexual orientation and age of onset, have been described; these display different developmental trajectories and prognoses. Prevalence studies conclude that fewer than 1 in 10,000 adult natal males and 1 in 30,000 adult natal females experience GD, but such estimates vary widely. GD in adults is associated with an elevated prevalence of comorbid psychopathology, especially mood disorders, anxiety disorders, and suicidality. Causal mechanisms in GD are incompletely understood, but genetic, neurodevelopmental, and psychosocial factors probably all contribute. Treatment of GD in adults, although largely standardized, is likely to evolve in response to the increasing diversity of persons seeking treatment, demands for greater client autonomy, and improved understanding of the benefits and limitations of current treatment modalities.

  4. Depression in Older Adults

    PubMed Central

    Fiske, Amy; Wetherell, Julie Loebach; Gatz, Margaret

    2010-01-01

    Depression is less prevalent among older adults than among younger adults but can have serious consequences. Over half of cases represent a first onset in later life. Although suicide rates in the elderly are declining, they are still higher than in younger adults and more closely associated with depression. Depressed older adults are less likely to endorse affective symptoms and more likely to display cognitive changes, somatic symptoms, and loss of interest than are younger adults. Risk factors leading to the development of late life depression likely comprise complex interactions among genetic vulnerabilities, cognitive diathesis, age-associated neurobiological changes, and stressful events. Insomnia is an often overlooked risk factor for late life depression. We suggest that a common pathway to depression in older adults, regardless of which predisposing risks are most prominent, may be curtailment of daily activities. Accompanying self-critical thinking may exacerbate and maintain a depressed state. Offsetting the increasing prevalence of certain risk factors in late life are age-related increases in psychological resilience. Other protective factors include higher education and socioeconomic status, engagement in valued activities, and religious or spiritual involvement. Treatments including behavioral therapy, cognitive behavioral therapy, cognitive bibliotherapy, problem-solving therapy, brief psychodynamic therapy, and life review/reminiscence therapy are effective but too infrequently used with older adults. Preventive interventions including education for individuals with chronic illness, behavioral activation, cognitive restructuring, problem-solving skills training, group support, and life review have also received support. PMID:19327033

  5. Mosquito, adult (image)

    MedlinePlus

    This illustration shows an adult southern house mosquito. This mosquito feeds on blood and is the carrier of many diseases, such as encephalitis, West Nile, dengue fever, yellow fever, and others. ( ...

  6. Older Adults and Alcohol

    MedlinePlus

    ... Alcohol Exposure Support & Treatment Alcohol Policy Special Populations & Co-occurring Disorders Publications & Multimedia Brochures & Fact Sheets NIAAA ... are here Home » Alcohol & Your Health » Special Populations & Co-occurring Disorders » Older Adults In this Section Underage ...

  7. Speech impairment (adult)

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/003204.htm Speech impairment (adult) To use the sharing features on ... 2017, A.D.A.M., Inc. Duplication for commercial use must be authorized in writing by ADAM ...

  8. Motivation and Adult Education

    ERIC Educational Resources Information Center

    Veeraraghavan, J.

    1974-01-01

    The paper examines the role of adult education and the contribution it can make to the solution of current problems in developing countries, particularly the problems of economic under-development and over-population. (Author/AG)

  9. Motivation and Adult Education.

    ERIC Educational Resources Information Center

    Taylor, J. Rodney

    1982-01-01

    The author reviews theories of human motivation: Lewin's force field analysis, Skinner's operant reinforcement theory, and Maslow's hierarchy of needs. He then extracts the implications of these theories for adult learning. SK)

  10. Older Adults and Depression

    MedlinePlus

    ... find more information? Reprints Share Older Adults and Depression Download PDF Download ePub Order a free hardcopy ... depression need treatment to feel better. Types of Depression There are several types of depression. The most ...

  11. Young Adult Books.

    ERIC Educational Resources Information Center

    Epstein, Connie C.

    1987-01-01

    Considers the similarities between science fiction writing and young adult literature, and points out that several well-known authors, such as Robert Heinlein and Jane Yolen, write in both genres. (NKA)

  12. Cardiac imaging in adults

    SciTech Connect

    Jaffe, C.C.

    1987-01-01

    This book approaches adult cardiac disease from the correlative imaging perspective. It includes chest X-rays and angiographs, 2-dimensional echocardiograms with explanatory diagrams for clarity, plus details on digital radiology, nuclear medicine techniques, CT and MRI. It also covers the normal heart, valvular heart disease, myocardial disease, pericardial disease, bacterial endocarditis, aortic aneurysm, cardiac tumors, and congenital heart disease of the adult. It points out those aspects where one imaging technique has significant superiority.

  13. Adult educators' core competences

    NASA Astrophysics Data System (ADS)

    Wahlgren, Bjarne

    2016-06-01

    Which competences do professional adult educators need? This research note discusses the topic from a comparative perspective, finding that adult educators' required competences are wide-ranging, heterogeneous and complex. They are subject to context in terms of national and cultural environment as well as the kind of adult education concerned (e.g. basic education, work-related education etc.). However, it seems that it is possible to identify certain competence requirements which transcend national, cultural and functional boundaries. This research note summarises these common or "core" requirements, organising them into four thematic subcategories: (1) communicating subject knowledge; (2) taking students' prior learning into account; (3) supporting a learning environment; and (4) the adult educator's reflection on his or her own performance. At the end of his analysis of different competence profiles, the author notes that adult educators' ability to train adult learners in a way which then enables them to apply and use what they have learned in practice (thus performing knowledge transfer) still seems to be overlooked.

  14. [Orthodontic treatment for adults].

    PubMed

    Kuitert, R B

    2000-04-01

    The number of adults undergoing orthodontic treatment has increased strongly and the average age that adult patients undergo orthodontic treatment increased steadily although 3/4 is still younger than 27 years. In adults the facial skeletal pattern can only be changed in a very confined way, consequently in case of an abnormal skeletal pattern one has to choose between a combined orthodontic-surgical approach (which is the case in 18% of the patients) and a compromised orthodontic treatment, if necessary combined with other disciplines. It is still controversial whether tooth movement in adults is slower and more difficult than in adolescents. The same holds true for the risk for loss of periodontal support, for root resorption, for gnathologic problems and for relapse. As related to these variables there appears to be a large individual variation. Many adults show one or more problems in their dentition that may influence their orthodontic treatment. About 60% of the adult patients need a multidisciplinary approach. The development of implantology and of bone regeneration and bone grafting has lead to more combined treatments. The risks of such complex treatment plans are generally larger than those for more simple kinds of treatment. A very careful treatment planning and good communication between the different specialists is essential. Moreover the treatment plan with all its (dis)advantages has to be extensively discussed with the patient.

  15. The State of Adult Education

    ERIC Educational Resources Information Center

    Fleming, Ted

    2004-01-01

    In this paper, the author looks at the state of adult education in Ireland. He is suggesting that the state here means both the condition in which one now finds adult education and the role of the Irish State in adult education. He briefly outlines some recent developments in adult education, makes some critical comments on the state of adult…

  16. The ABC's of Adult Ed

    ERIC Educational Resources Information Center

    Roehrig, Lucy

    2010-01-01

    According to the 2003 National Assessment of Adult Literacy, it is estimated that 93 million adults in the United States have basic or below basic literacy skills. Those individuals found most lacking in literacy skills were adults living in poverty, adults lacking a high school diploma, seniors and the elderly aged 65 and older, the more than one…

  17. Designing an Adult Education Program.

    ERIC Educational Resources Information Center

    Rand, Margaret

    Intended for planners of adult education curriculums, this literature review explains the concepts involved in designing an adult education program, provides information about the roles of the people involved in the adult education process, cites some program planning models, and applies the program planning principles to an Adult Basic Education…

  18. The Adult Learner: Four Aspects.

    ERIC Educational Resources Information Center

    Lucas, John A., Ed.

    1986-01-01

    Topics concerning the adult learner that are relevant to institutional researchers are addressed in four articles: marketing, predicting success for adult students, enrollment projection, and follow-up studies of adult learners. In "Institutional Research in Support of Marketing the Adult Student," Lydia Jurand notes the importance of…

  19. Rich Environments for Adult Learners

    ERIC Educational Resources Information Center

    Bentham, Renee

    2008-01-01

    Unaware of the messages a bare adult learning environment sends and its effect on adult learners, a trainer attends an intensive Reggio Emilia course and learns that the physical environment is the "third teacher"--for adults as well as for children. Using principles of Reggio, she offers suggestions for enhancing adult learning spaces and…

  20. Posterior Fossa Tumors.

    PubMed

    Brandão, Lara A; Young Poussaint, Tina

    2017-02-01

    Pediatric brain tumors are the leading cause of death from solid tumors in childhood. The most common posterior fossa tumors in children are medulloblastoma, atypical teratoid/rhabdoid tumor, cerebellar pilocytic astrocytoma, ependymoma, and brainstem glioma. Location, and imaging findings on computed tomography (CT) and conventional MR (cMR) imaging may provide important clues to the most likely diagnosis. Moreover, information obtained from advanced MR imaging techniques increase diagnostic confidence and help distinguish between different histologic tumor types. Here we discuss the most common posterior fossa tumors in children, including typical imaging findings on CT, cMR imaging, and advanced MR imaging studies.

  1. Long-tunnelled external ventricular drain as a long-term treatment option for hydrocephalus in a child with an unresectable low-grade supratentorial tumor: case report.

    PubMed

    Emelifeonwu, John A; Sokol, Drahoslav; Gallo, Pasquale; Kandasamy, Jothy; Kaliaperumal, Chandrasekaran

    2016-10-01

    The authors report a case of a child with hypothalamic-origin pilocytic astrocytoma and hydrocephalus, which was refractory to treatment with a ventriculoperitoneal shunt due to high CSF protein content. With parental education, the child's hydrocephalus was managed long-term in the community with a long-tunnelled external ventricular drain, which was maintained by his parents. To the authors' knowledge this is the first report of this management option as a long-term measure. No harm has come to the patient. The authors propose long-term, long-tunnelled external ventricular drain as a viable treatment option for such patients.

  2. Adult-onset Atopic Dermatitis

    PubMed Central

    Kanwar, Amrinder Jit

    2016-01-01

    Adult-onset atopic dermatitis is still an under recognized condition as there are only few studies regarding this entity. As compared to childhood onset atopic dermatitis, clinical features of adult onset atopic dermatitis are still not categorized. Adult atopic dermatitis can present for the first time in adult age with atypical morphology or may progress from childhood onset. This article reviews the characteristic clinical features of adult atopic dermatitis, associated risk factors and management. PMID:27904186

  3. Adult onset retinoblastoma

    PubMed Central

    Sengupta, Sabyasachi; Pan, Utsab; Khetan, Vikas

    2016-01-01

    Retinoblastoma (RB) is the most common primary malignant intraocular tumor of childhood presenting usually before 5 years of age. RB in adults older than 20 years is extremely rare. A literature search using PubMed/PubMed Central, Scopus, Google Scholar, EMBASE, and Cochrane databases revealed only 45 cases till date. Over the past decade, there has been a significant increase in the number of such reports, indicating heightened level of suspicion among ophthalmologists. Compared to its pediatric counterpart, adult onset RB poses unique challenges in diagnosis and treatment. This article summarizes available literature on adult onset RB and its clinical and pathologic profile, genetics, association with retinocytoma, diagnostics, treatment, and outcomes. PMID:27609158

  4. Adult Seborrheic Dermatitis

    PubMed Central

    2011-01-01

    Seborrheic dermatitis is a common chronic-recurrent inflammatory disorder that most commonly affects adults; however, a more transient infantile form also occurs. The definitive cause of seborrheic dermatitis is unknown. However, proliferation of Malassezia species has been described as a contributing factor. The adult form of seborrheic dermatitis affects up to approximately five percent of the general population. The disorder commonly affects the scalp, face, and periauricular region, with the central chest, axillae, and genital region also involved in some cases. Pruritus is not always present and is relatively common, especially with scalp disease. A variety of treatments are available including topical corticosteroids, topical antifungal agents, topical calcineurin inhibitors, and more recently, a nonsteroidal “device ”cream. This article reviews the practical topical management of seborrheic dermatitis in the United States, focusing on the adult population. PMID:21607192

  5. Electroporation of adult zebrafish.

    PubMed

    Rao, N Madhusudhana; Rambabu, K Murali; Rao, S Harinarayana

    2008-01-01

    We generated transient transgenic zebrafish by applying electrical pulses subsequent to injection of DNA into muscle tissue of 3-6-month old adult zebrafish. Electroporation parameters, such as number of pulses, voltage, and amount of plasmid DNA, were optimized and found that 6 pulses of 40 V/cm at 15 mug/fish increased the luciferase expression by 10-fold compared with those in controls. By measuring the expression of luciferase, in vivo by electroporation in adult zebrafish and in vitro using fish cell line (Xiphophorus xiphidium A2 cells), the strength of three promoters (CMV, human EF-1alpha, and Xenopus EF-1alpha) was compared. Subsequent to electroporation after injecting DNA in the mid region of zebrafish, expression of green fluorescent protein was found far away from the site of injection in the head and the tail sections. Thus, electroporation in adult zebrafish provides a rapid way of testing the behavior of gene sequences in the whole organism.

  6. Back pain in adults.

    PubMed

    Becker, Jonathan A; Stumbo, Jessica R

    2013-06-01

    This article provides a summary of the many causes of back pain in adults. There is an overview of the history and physical examination with attention paid to red flags that alert the clinician to more worrisome causes of low back pain. An extensive differential diagnosis for back pain in adults is provided along with key historical and physical examination findings. The various therapeutic options are summarized with an emphasis on evidence-based findings. These reviewed treatments include medication, physical therapy, topical treatments, injections, and complementary and alternative medicine. The indications for surgery and specialty referral are also discussed.

  7. [Adult oligosymptomatic coeliac disease].

    PubMed

    Cabral Rodríguez, R; Arrieta Blanco, F J; Vicente Sánchez, F; Cordobés Martín, F J; Moreno Caballero, B

    2004-12-01

    Coeliac disease is a chronic pathology of the small intestine. The pathogenic mechanism is caused by gluten intolerance. This disease present a characteristic and unspecific injury that causes nutrients and vitamins malabsorption. In adults is an underdiagnosed entity due to atypical forms. To make a premature diagnosis is basic because gluten-free diet prevent the complications after long-term like the intestinal T lymphoma and other digestives malignancies, and decrease the mortality of these patients. We present a case of adult oligosymptomatic coeliac disease in a patient with iron deficiency anaemia and vaginal bleeding. We study the clinic-nutrition and the alterations evolution of the patient.

  8. Adult Learning Matters

    ERIC Educational Resources Information Center

    Adults Learning, 2009

    2009-01-01

    The Campaigning Alliance for Lifelong Learning is to lobby parliament for the restoration of the 1.5 million adult learning places lost over the past two years. The campaign has attracted supporters from an astonishingly wide range of backgrounds. In this article, Gordon Marsden, Caroline Biggins, Beth Walker, Mike Chaney, Peter Davies, Sian…

  9. Facilitation of Adult Development

    ERIC Educational Resources Information Center

    Boydell, Tom

    2016-01-01

    Taking an autobiographical approach, I tell the story of my experiences facilitating adult development, in a polytechnic and as a management consultant. I relate these to a developmental framework of Modes of Being and Learning that I created and elaborated with colleagues. I connect this picture with a number of related models, theories,…

  10. Hearing Loss in Adults.

    ERIC Educational Resources Information Center

    House, John W.

    1997-01-01

    This article discusses hearing loss in adults. It begins with an explanation of the anatomy of the ear and then explains the three types of hearing loss: conductive hearing loss, sensorineural hearing loss, and mixed conductive-sensorineural hearing loss. Tinnitus, hearing aids, and cochlear implants are also addressed. (CR)

  11. Older Adult Education.

    ERIC Educational Resources Information Center

    Forman, Jeffrey

    In an effort to improve the quality of life for area senior citizens, De Anza College has established an older adult education program which combines adaptive physical education with holistic health care principles to instruct students in relaxation, nutrition, and physical activity. Classes are held in convalescent hospitals, retirement homes,…

  12. Adult Education in Brazil.

    ERIC Educational Resources Information Center

    Ministerio da Educacao e Cultura, Rio de Janeiro (Brazil).

    The status and goals of adult education programs in Brazil are discussed in this report. Supplemental systems such as the Brazilian Literacy Movement (Mobral) and their results are described and evaluated. Charts detailing the evolution of literacy are shown and priorities in education are suggested. The progress of other educational entities is…

  13. Adult Basic Education Curriculum.

    ERIC Educational Resources Information Center

    Massachusetts Career Development Inst., Springfield.

    This booklet, aimed at adult basic education students, pinpoints and summarizes a few common spelling rules to help make spelling easier, and includes a component on using the dictionary. In the text, each rule is presented with many examples. Exercises follow each spelling rule, allowing students the opportunity to apply the rule to specific…

  14. Police and Adult Education.

    ERIC Educational Resources Information Center

    Sims, Vic

    The literature on adult education for police is reviewed and criticized. Among the publications that have been influential in debating the need for police education are Charles B. Saunder's "The Challenge of Crime in a Free Society" (1976), which endorses the Presidential Commission on Law Enforcement's recommendations regarding the vital…

  15. Dance for Older Adults.

    ERIC Educational Resources Information Center

    Pruett, Diane Milhan, Ed.; And Others

    1983-01-01

    Dance programs for older adults that encourage exercise and socializing are described in six articles. Program guidelines of the American Alliance Committee on Aging are explained, and other articles emphasize a movement education approach that may involve intergenerational contact. A dance program held in a worship setting is also discussed. (PP)

  16. Migration and Adult Education

    ERIC Educational Resources Information Center

    Gois, William

    2007-01-01

    The objective of this paper is to highlight the role of adult education as a tool in addressing labour migration issues, specifically those concerning the protection of migrant workers' rights and the transformation of the impact of migration into positive holistic developmental gains. The view of labour migration as a means to forge the economic…

  17. How Do Adults Learn?

    ERIC Educational Resources Information Center

    Rogers, Alan; Illeris, Knud

    2003-01-01

    This dialog between Alan Rogers and Knud Illeris debates arguments Rogers made in a previous article about the differences between adult and child learning. Rogers emphasizes differences in teacher-learner relationships. Illeris believes the differences result from different motivations for learning. (SK)

  18. Encyclopedia of Adult Development.

    ERIC Educational Resources Information Center

    Kastenbaum, Robert, Ed.

    This encyclopedia contains 106 articles on adult development that were written by more than 75 specialists in such diverse fields as anthropology, communication, education, health sciences, history, and psychology. In a guide to related topics that is presented at the beginning of the encyclopedia, the 106 articles are grouped under the following…

  19. Sinusitis in adults - aftercare

    MedlinePlus

    ... this page: //medlineplus.gov/ency/patientinstructions/000563.htm Sinusitis in adults - aftercare To use the sharing features on this page, please enable JavaScript. Your sinuses are chambers in ... They are filled with air. Sinusitis is an infection of these chambers, which causes ...

  20. Helping Adults to Spell.

    ERIC Educational Resources Information Center

    Moorhouse, Catherine

    This book presents a range of strategies for adult literacy tutors and offers a wealth of practical advice on teaching spelling within the context of writing. Chapters 1-3 offer basic information on talking with the student about spelling, finding out how the student spells and helping the student to see himself/herself as a "good" speller, and…

  1. Immigration and Adult Transitions

    ERIC Educational Resources Information Center

    Rumbaut, Ruben G.; Komaie, Golnaz

    2010-01-01

    Almost 30 percent of the more than 68 million young adults aged eighteen to thirty-four in the United States today are either foreign born or of foreign parentage. As these newcomers make their transitions to adulthood, say Ruben Rumbaut and Golnaz Komaie, they differ significantly not only from one another but also from their native-parentage…

  2. Profiles of Adult Learners.

    ERIC Educational Resources Information Center

    Illinois State Library, Springfield.

    Since January 1986, when the Illinois Secretary of State Literacy Grant Program began funding a wide variety of adult literacy programs, more than 30,000 students have sought help with reading. They have been matched with 25,000 tutors who have provided more than 2 million hours of volunteer instruction. The profiles in this booklet are stories of…

  3. Adult Literacy Perspectives.

    ERIC Educational Resources Information Center

    Taylor, Maurice C., Ed.; Draper, James A., Ed.

    This book, intended to serve as a professional reference work, proposes to define the field of Adult Basic Education in its evolution, its contribution to professional education, and the principal problems and issues. The volume contains the following treatises: "Definitions and Evolution of the Concepts" (Thomas); "Selected…

  4. Depression - older adults

    MedlinePlus

    ... slowly than in younger adults. To better manage depression at home: Exercise regularly, if the provider says it is OK. Surround yourself with caring, positive people and do fun activities. ... signs of depression, and know how to react if these occur. ...

  5. TRENDS IN ADULT READING.

    ERIC Educational Resources Information Center

    MILLER, JUSTIN H.

    TRENDS EVIDENT IN ADULT READING DURING THE 1960'S IN THE AREAS OF ADMINISTRATION, PROGRAMS, TEACHING, TECHNIQUES, RESEARCH PROJECTS, AND METHODS OF PROMOTION OF READING PROGRAMS ARE DISCUSSED. TWO INSTANCES OF COMMERCIAL EXPLOITATION BASED ON INTENSE AND OFTEN FALLACIOUS ADVERTISING AND ON PUBLIC IGNORANCE ARE CITED. A POSITIVE TREND IN THE AREA…

  6. Newly Diagnosed: Older Adults

    MedlinePlus

    ... Children Newly Diagnosed: Older Adults Related Topics on AIDS.gov Aging with HIV/AIDS National HIV/AIDS ... an Emerging Challenge Last revised: 07/10/2015 AIDS.gov HIV/AIDS Basics • Federal Resources • Using New ...

  7. Utah Adult Education Services. Adult Education Report 1968-69.

    ERIC Educational Resources Information Center

    Utah State Board of Education, Salt Lake City.

    Major purposes for the preparation of this report on public school adult education in Utah were: to provide the public with a description of achievements, trends, and needs, and with meaningful cost accounting information; to make comparisons and analyses of adult education by program, school district, and year; and to provide the adult education…

  8. What is Young Adult Literature? (Young Adult Literature).

    ERIC Educational Resources Information Center

    Crowe, Chris, Ed.

    1998-01-01

    Outlines some of the many confusions about young adult literature. Sheds some light on what young adult literature is (defining it as all genres of literature published since 1967 that are written for and marketed to young adults). Discusses briefly how it can be used in schools. Offers a list of the author's 20 favorite books for teenagers. (SR)

  9. Teaching Nontraditional Adult Students: Adult Learning Theories in Practice

    ERIC Educational Resources Information Center

    Chen, Joseph C.

    2014-01-01

    As the USA experiences rapid growth of nontraditional adult students in higher education, educators and institutions will increasingly need to look beyond the traditional youth-centric educational models to better address adult learning needs. To date, no research has been conducted examining the learning experiences of adult students enrolled in…

  10. Congenital Heart Disease in Adults

    MedlinePlus

    ... and genetics may play a role. Why congenital heart disease resurfaces in adulthood Some adults may find that ... in following adults with congenital heart disease. Congenital heart disease and pregnancy Women with congenital heart disease who ...

  11. Adult Education for Social Mobilization.

    ERIC Educational Resources Information Center

    Echeverria, Luis

    1981-01-01

    Suggests some ideas that could stimulate and be incentives for defining programs of adult education in the future. These involve changing priorities, developing a framework which allows adult education programs to be established, and managing decision-making processes. (CT)

  12. College-Age & Young Adults

    MedlinePlus

    ... Adolescent Brain Comorbidity College-Age & Young Adults Criminal Justice Drugged Driving Drug Testing Drugs and the Brain ... Age & Young Adults College Addiction Studies Programs Criminal Justice Drugged Driving Drug Testing Drugs and the Brain ...

  13. Renal Disease and Adult Vaccination

    MedlinePlus

    ... Resources for Healthcare Professionals Renal Disease and Adult Vaccination Recommend on Facebook Tweet Share Compartir Vaccines are ... have immunity to this disease Learn about adult vaccination and other health conditions Asplenia Diabetes Type 1 ...

  14. Alcohol Use and Older Adults

    MedlinePlus

    ... version of this page please turn Javascript on. Alcohol Use and Older Adults Alcohol and Aging Adults of any age can have ... Escape (Esc) button on your keyboard.) What Is Alcohol? Alcohol, also known as ethanol, is a chemical ...

  15. Liver Disease and Adult Vaccination

    MedlinePlus

    ... Vaccination Recommendations Adult Vaccination Resources for Healthcare Professionals Liver Disease and Adult Vaccination Recommend on Facebook Tweet ... critical for people with health conditions such as liver disease. If you have chronic liver disease, talk ...

  16. Enhancing Older Adults' Reading Comprehension.

    ERIC Educational Resources Information Center

    Kemper, Susan; And Others

    1993-01-01

    Investigates older adults' reading comprehension skills through syntactic measures and measures of sentence content. Analyzes the apparent reading difficulties of older adults. Provides guidelines for the preparation of prose materials for older readers. (HB)

  17. Adult Development and the Workplace.

    ERIC Educational Resources Information Center

    Heffernan, James M.

    Little attention has been given to how adults develop through their lifetimes and what roles their workplace environments play in that development. Research and theory regarding adult psychosocial development have confirmed the developmental life-cycle phases of adulthood. These are: leaving the family (ages 16-22), getting into the adult world…

  18. Facilitating Creativity in Adult Learners

    ERIC Educational Resources Information Center

    Tsai, Kuan Chen

    2013-01-01

    Creativity in education research has received increasing attention, although the major focus of this research has been on children. Despite pleas by several adult educators for promoting creativity, very few studies have focused on adult learners, leaving to it to be explored what approaches are useful for adult educators to facilitate creativity…

  19. Adult Learning. ARIS Information Sheet.

    ERIC Educational Resources Information Center

    National Languages and Literacy Inst. of Australia, Melbourne. Adult Education Resource and Information Service.

    This information sheet provides a summary of general observations regarding adult learners. Adults from different walks of life may seek out learning at different times in their lives, for different reasons, and for vastly different purposes. Adult learning groups may include students of different ages, cultures, and educational and socioeconomic…

  20. Assessment Tools for Adult Education.

    ERIC Educational Resources Information Center

    Shefrin, Carol; Shafer, Dehra; Forlizzi, Lori

    The Assessment Tools for Adult Education project was designed to provide training and support to staff of the Pennsylvania Bureau of Adult Basic and Literacy Education (ABLE) funded programs to help them use assessment tools and procedures to document the learning gains of the adult students they serve. The following candidate assessment…

  1. The Politics of Adult Education

    ERIC Educational Resources Information Center

    Adam, Roy

    1974-01-01

    All educational levels have been attacked by politicians and haunted by suspicion, and adult education has drawn more than its share. Interest groups have had a large effect on adult education. The construction of a theoretical model of the politics of adult education is suggested. (DS)

  2. Adult Multiple Intelligences and Math.

    ERIC Educational Resources Information Center

    Costanzo, Meg Ryback

    In the Adult Multiple Intelligences (AMI) study, 10 teachers of adults from the northeastern region of the United States explored for 18 months the ways that multiple intelligences (MI) theory could support instruction and assessment in various adult learning contexts. The results of this research were published in a book by Julie Viens called MI…

  3. New Thrusts in Adult Education.

    ERIC Educational Resources Information Center

    Worthington, Robert M.

    The Associate Commissioner of the Bureau of Adult, Vocational, and Technical Education is responsible for two broad and important programs, career education and broader and better services in adult education. Career education is a lifelong educational process beginning in kindergarten and extending through adult and continuing education. Career…

  4. Adult Education and Development, 1994.

    ERIC Educational Resources Information Center

    Adult Education and Development, 1994

    1994-01-01

    The publication is a half-yearly journal for adult education in Africa, Asia, and Latin America. Issue 42 includes the following: "Adult Education for Self-Reliance in Community Health Education Programmes" (Kweka); "Promoting Good Nutrition" (Mangvwat); "Incorporating Health-Improvement Activities in Adult Education…

  5. Adult Learning and HRD. Symposium.

    ERIC Educational Resources Information Center

    2002

    This symposium on adult learning and human resource development consists of three presentations. "Adult Learning Principles and Concepts in the Workplace: Implications for Training in HRD" (Margot B. Weinstein) reports on findings from interviews with restaurant employees who reported that training practices using adult learning…

  6. Adult Education through World Collaboration.

    ERIC Educational Resources Information Center

    Cassara, Beverly Benner, Ed.

    This book contains the following papers about development/delivery of adult education through the efforts of multinational and bilateral government donors and the International Council for Adult Education (ICAE): "Preface" (Beverly Benner Cassara); "Introduction: Adult Education and Democracy" (Francisco Vio Grossi);…

  7. Diarrhoea in adults (acute)

    PubMed Central

    2011-01-01

    Introduction An estimated 4.6 billion cases of diarrhoea occurred worldwide in 2004, resulting in 2.2 million deaths. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for acute diarrhoea in adults living in resource-rich countries? What are the effects of treatments for acute mild-to-moderate diarrhoea in adults from resource-rich countries travelling to resource-poor countries? What are the effects of treatments for acute mild-to-moderate diarrhoea in adults living in resource-poor countries? What are the effects of treatments for acute severe diarrhoea in adults living in resource-poor countries? We searched: Medline, Embase, The Cochrane Library, and other important databases up to January 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 72 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotics, antimotility agents, antisecretory agents, bismuth subsalicylate, diet, intravenous rehydration, nasogastric tube rehydration, oral rehydration solutions (amino acid oral rehydration solution, bicarbonate oral rehydration solution, reduced osmolarity oral rehydration solution, rice-based oral rehydration solution, standard oral rehydration solution), vitamin A supplementation, and zinc supplementation. PMID:21718555

  8. Increased fluorine-18 2-fluoro-2-deoxy-D-glucose (FDG) uptake in childhood CNS tumors is correlated with malignancy grade: a study with FDG positron emission tomography/magnetic resonance imaging coregistration and image fusion.

    PubMed

    Borgwardt, Lise; Højgaard, Liselotte; Carstensen, Henrik; Laursen, Henning; Nowak, Markus; Thomsen, Carsten; Schmiegelow, Kjeld

    2005-05-01

    PURPOSE Positron emission tomography (PET) has been used in grading of CNS tumors in adults, whereas studies of children have been limited. PATIENTS AND METHODS Nineteen boys and 19 girls (median age, 8 years) with primary CNS tumors were studied prospectively by fluorine-18 2-fluoro-2-deoxy-D-glucose (FDG) PET with (n = 16) or without (n = 22) H(2)(15)O-PET before therapy. Image processing included coregistration to magnetic resonance imaging (MRI) in all patients. The FDG uptake in tumors was semiquantitatively calculated by a region-of-interest-based tumor hotspot/brain index. Eight tumors without histologic confirmation were classified as WHO grade 1 based on location, MRI, and clinical course (22 to 42 months). Results Four grade 4 tumors had a mean index of 4.27 +/- 0.5, four grade 3 tumors had a mean index of 2.47 +/- 1.07, 10 grade 2 tumors had a mean index of 1.34 +/- 0.73, and eight of 12 grade 1 tumors had a mean index of -0.31 +/- 0.59. Eight patients with no histologic confirmation had a mean index of 1.04. For these 34 tumors, FDG uptake was positively correlated with malignancy grading (n = 34; r = 0.72; P < .01), as for the 26 histologically classified tumors (n = 26; r = 0.89; P < .01). The choroid plexus papilloma (n = 1) and the pilocytic astrocytomas (n = 3) had a mean index of 3.26 (n = 38; r = 0.57; P < .01). H(2)(15)O-uptake showed no correlation with malignancy. Digitally performed PET/MRI coregistration increased information on tumor characterization in 90% of cases. CONCLUSION FDG PET of the brain with MRI coregistration can be used to obtain a more specific diagnosis with respect to malignancy grading. Improved PET/MRI imaging of the benign hypermetabolic tumors is needed to optimize clinical use.

  9. CDC Vital Signs: Adults with Disabilities

    MedlinePlus

    ... Problem More adults with disabilities need to get physical activity. Adults with disabilities who get no physical activity ... Adults with disabilities are more likely to get physical activity if doctors recommend it. Only 44% of adults ...

  10. An Undergraduate Course in Adult Development: When the Virtual Adult Is an Adult

    ERIC Educational Resources Information Center

    Williams, Robert B.

    2014-01-01

    An aspect of an undergraduate psychology course on adult development was the preparation of case records on adults who consented to be studied. Participants (1) developed their abilities to observe and accurately record adult behavior across a variety of ages and contexts; (2) withheld judgments about behavior when evidence was lacking; (3)…

  11. Updated therapeutic strategy for adult low-grade glioma stratified by resection and tumor subtype.

    PubMed

    Nitta, Masayuki; Muragaki, Yoshihiro; Maruyama, Takashi; Iseki, Hiroshi; Ikuta, Soko; Konishi, Yoshiyuki; Saito, Taichi; Tamura, Manabu; Chernov, Michael; Watanabe, Atsushi; Okamoto, Saori; Maebayashi, Katsuya; Mitsuhashi, Norio; Okada, Yoshikazu

    2013-01-01

    The importance of surgical resection for patients with supratentorial low-grade glioma (LGG) remains controversial. This retrospective study of patients (n = 153) treated between 2000 to 2010 at a single institution assessed whether increasing the extent of resection (EOR) was associated with improved progression-free survival (PFS) and overall survival (OS). Histological subtypes of World Health Organization grade II tumors were as follows: diffuse astrocytoma in 49 patients (32.0%), oligoastrocytoma in 45 patients (29.4%), and oligodendroglioma in 59 patients (38.6%). Median pre- and postoperative tumor volumes and median EOR were 29.0 cm(3) (range 0.7-162 cm(3)) and 1.7 cm(3) (range 0-135.7 cm(3)) and 95%, respectively. Five- and 10-year OS for all LGG patients were 95.1% and 85.4%, respectively. Eight-year OS for diffuse astrocytoma, oligoastrocytoma, and oligodendroglioma were 70.7%, 91.2%, and 98.3%, respectively. Five-year PFS for diffuse astrocytoma, oligoastrocytoma, and oligodendroglioma were 42.6%, 71.3%, and 62.7%, respectively. Patients were divided into two groups by EOR ≥90% and <90%, and OS and PFS were analyzed. Both OS and PFS were significantly longer in patients with ≥90% EOR. Increased EOR resulted in better PFS for diffuse astrocytoma but not for oligodendroglioma. Multivariate analysis identified age and EOR as parameters significantly associated with OS. The only parameter associated with PFS was EOR. Based on these findings, we established updated therapeutic strategies for LGG. If surgery resulted in EOR <90%, patients with astrocytoma will require second-look surgery, whereas patients with oligodendroglioma or oligoastrocytoma, which are sensitive to chemotherapy, will be treated with chemotherapy.

  12. The adult scoliosis.

    PubMed

    Aebi, Max

    2005-12-01

    Adult scoliosis is defined as a spinal deformity in a skeletally mature patient with a Cobb angle of more than 10 degrees in the coronal plain. Adult scoliosis can be separated into four major groups: Type 1: Primary degenerative scoliosis, mostly on the basis of a disc and/or facet joint arthritis, affecting those structures asymmetrically with predominantly back pain symptoms, often accompanied either by signs of spinal stenosis (central as well as lateral stenosis) or without. These curves are often classified as "de novo" scoliosis. Type 2: Idiopathic adolescent scoliosis of the thoracic and/or lumbar spine which progresses in adult life and is usually combined with secondary degeneration and/or imbalance. Some patients had either no surgical treatment or a surgical correction and fusion in adolescence in either the thoracic or thoracolumbar spine. Those patients may develop secondary degeneration and progression of the adjacent curve; in this case those curves belong to the type 3a. Type 3: Secondary adult curves: (a) In the context of an oblique pelvis, for instance, due to a leg length discrepancy or hip pathology or as a secondary curve in idiopathic, neuromuscular and congenital scoliosis, or asymmetrical anomalies at the lumbosacral junction; (b) In the context of a metabolic bone disease (mostly osteoporosis) combined with asymmetric arthritic disease and/or vertebral fractures. Sometimes it is difficult to decide, what exactly the primary cause of the curve was, once it has significantly progressed. However, once an asymmetric load or degeneration occurs, the pathomorphology and pathomechanism in adult scoliosis predominantly located in the lumbar or thoracolumbar spine is quite predictable. Asymmetric degeneration leads to increased asymmetric load and therefore to a progression of the degeneration and deformity, as either scoliosis and/or kyphosis. The progression of a curve is further supported by osteoporosis, particularly in post-menopausal female

  13. Adult respiratory distress syndrome.

    PubMed

    Cutts, S; Talboys, R; Paspula, C; Prempeh, E M; Fanous, R; Ail, D

    2017-01-01

    Adult respiratory distress syndrome (ARDS) has now been described as a sequela to such diverse conditions as burns, amniotic fluid embolism, acute pancreatitis, trauma, sepsis and damage as a result of elective surgery in general. Patients with ARDS require immediate intubation, with the average patient now being ventilated for between 8 and 11 days. While the acute management of ARDS is conducted by the critical care team, almost any surgical patient can be affected by the condition and we believe that it is important that a broader spectrum of hospital doctors gain an understanding of the nature of the pathology and its current treatment.

  14. Adult hereditary fructose intolerance.

    PubMed

    Burmeister, L A; Valdivia, T; Nuttall, F Q

    1991-04-01

    Hereditary fructose intolerance was diagnosed in a 69-year-old man on the basis of his medical history and the response to an intravenous fructose tolerance test. Three men of the same age as our patient were used as control subjects. Since the severity may vary and affected individuals self-impose fructose and sucrose restriction, they are essentially symptom free. The diagnosis can only be suspected by taking a careful dietary history. The prevalence of this condition in adults is unknown. It is rare but is likely to be more common than data in the literature would indicate.

  15. Intestinal lymphangiectasia in adults.

    PubMed

    Freeman, Hugh James; Nimmo, Michael

    2011-02-15

    Intestinal lymphangiectasia in the adult may be characterized as a disorder with dilated intestinal lacteals causing loss of lymph into the lumen of the small intestine and resultant hypoproteinemia, hypogammaglobulinemia, hypoalbuminemia and reduced number of circulating lymphocytes or lymphopenia. Most often, intestinal lymphangiectasia has been recorded in children, often in neonates, usually with other congenital abnormalities but initial definition in adults including the elderly has become increasingly more common. Shared clinical features with the pediatric population such as bilateral lower limb edema, sometimes with lymphedema, pleural effusion and chylous ascites may occur but these reflect the severe end of the clinical spectrum. In some, diarrhea occurs with steatorrhea along with increased fecal loss of protein, reflected in increased fecal alpha-1-antitrypsin levels, while others may present with iron deficiency anemia, sometimes associated with occult small intestinal bleeding. Most lymphangiectasia in adults detected in recent years, however, appears to have few or no clinical features of malabsorption. Diagnosis remains dependent on endoscopic changes confirmed by small bowel biopsy showing histological evidence of intestinal lymphangiectasia. In some, video capsule endoscopy and enteroscopy have revealed more extensive changes along the length of the small intestine. A critical diagnostic element in adults with lymphangiectasia is the exclusion of entities (e.g. malignancies including lymphoma) that might lead to obstruction of the lymphatic system and "secondary" changes in the small bowel biopsy. In addition, occult infectious (e.g. Whipple's disease from Tropheryma whipplei) or inflammatory disorders (e.g. Crohn's disease) may also present with profound changes in intestinal permeability and protein-losing enteropathy that also require exclusion. Conversely, rare B-cell type lymphomas have also been described even decades following initial

  16. Immigration and adult transitions.

    PubMed

    Rumbaut, Rubén G; Komaie, Golnaz

    2010-01-01

    Almost 30 percent of the more than 68 million young adults aged eighteen to thirty-four in the United States today are either foreign born or of foreign parentage. As these newcomers make their transitions to adulthood, say Rubén Rumbaut and Golnaz Komaie, they differ significantly not only from one another but also from their native-parentage counterparts, including blacks and whites. The authors document the demographic changes in the United States over the past forty years and describe the ways in which generation and national origin shape the experiences of these newcomers as they become adults. Rumbaut and Komaie point out that immigrant groups experience gaps in social, economic, and legal status that are even greater than the gaps between native whites and blacks. By far the most-educated (Indians) and the least-educated (Mexicans) groups in the United States today are first-generation immigrants, as are the groups with the lowest poverty rate (Filipinos) and the highest poverty rate (Dominicans). These social and economic divides reflect three very different ways immigrants enter the country: through regular immigration channels, without legal authorization, or as state-sponsored refugees. For many ethnic groups, significant progress takes place from the first to the second generation. But, say the authors, for millions of young immigrants, a lack of legal permanent residency status blocks their prospects for social mobility. Having an undocumented status has become all the more consequential with the failure of Congress to pass comprehensive federal immigration reforms. In the coming two decades, as the U.S. native-parentage labor force continues to shrink, immigrants and their children are expected to account for most of the growth of the nation's labor force, with the fastest-growing occupations requiring college degrees. Rumbaut and Komaie stress that one key to the nation's future will be how it incorporates young adults of immigrant origin in its

  17. [Hearing loss in adults].

    PubMed

    Eshraghi, Adrien A; Frachet, Bruno; Van De Water, Tom R; Eter, Elias

    2009-05-20

    The management of hearing loss in adults depends of etiology and its severity. It can be as simple as treating an external otitis, removing an impacted cerumen or a more complex one such as a surgery for otosclerosis. The hearing loss is managed mainly by new advances in hearing aids technology and implantable hearing devices which include BAHA, middle ear implant and cochlear implants. The research is focused on developing new molecules for intracochlear drug therapy to treat noise induced hearing loss, drug ototoxicity as well as hearing loss related to cochlear implant insertion trauma. Antioxidant molecules, molecules against apoptosis are at this time the most promising molecules than need further investigations.

  18. [Genetics and brain gliomas].

    PubMed

    Alentorn, Agusti; Labussière, Marianne; Sanson, Marc; Delattre, Jean-Yves; Hoang-Xuan, Khê; Idbaih, Ahmed

    2013-05-01

    Chromosome arms 1p and 19q codeletion, corresponding to an unbalanced reciprocal translocation t(1;19)(q10;p10), is seen in oligodendroglial tumours and is associated with better prognosis and better chemosensitivity. BRAF abnormalities are observed in pilocytic astrocytomas (tandem duplication-rearrangement) and in pleomorphic xanthoastrocytomas (BRAF V600E mutation). The vast majority of primary or de novo glioblastomas exhibit genetic abnormalities disrupting the intracellular signaling pathways of: transmembrane tyrosine kinase receptors to growth factors and their downstream signaling pathways (i.e. NF1-RAS-RAF-MAPK and PTEN-PI3K-AKT-TSC-mTOR); RB and; TP53. IDH1 and IDH2 mutations are frequent in diffuse grade II and grade III gliomas and in secondary glioblastomas. They are diagnostic and favorable independent prognostic biomarkers. In contrast, they are rare in primary or de novo glioblastomas and not reported in pilocytic astrocytomas. Germlin mutations in MSH2/MLH1/PMS2/MSH6, CDKN2A, TSC1/TSC2, PTEN, TP53 and NF1/NF2 predispose to glial tumors in the setting of hereditary cancer predisposition syndromes. Single nucleotide polymorphisms in TERT,CCDC26, CDKN2A/CDKN2B, RTEL, EGFR and PHLDB1 confer an inherited susceptibility to glial tumors.

  19. Detection of KIAA1549-BRAF Fusion Transcripts in Formalin-Fixed Paraffin-Embedded Pediatric Low-Grade Gliomas

    PubMed Central

    Tian, Yongji; Rich, Benjamin E.; Vena, Natalie; Craig, Justin M.; MacConaill, Laura E.; Rajaram, Veena; Goldman, Stewart; Taha, Hala; Mahmoud, Madeha; Ozek, Memet; Sav, Aydin; Longtine, Janina A.; Lindeman, Neal I.; Garraway, Levi A.; Ligon, Azra H.; Stiles, Charles D.; Santagata, Sandro; Chan, Jennifer A.; Kieran, Mark W.; Ligon, Keith L.

    2011-01-01

    Alterations of BRAF are the most common known genetic aberrations in pediatric gliomas. They frequently are found in pilocytic astrocytomas, where genomic duplications involving BRAF and the poorly characterized gene KIAA1549 create fusion proteins with constitutive B-Raf kinase activity. BRAF V600E point mutations are less common and generally occur in nonpilocytic tumors. The development of BRAF inhibitors as drugs has created an urgent need for robust clinical assays to identify activating lesions in BRAF. KIAA1549-BRAF fusion transcripts have been detected in frozen tissue, however, methods for FFPE tissue have not been reported. We developed a panel of FFPE-compatible quantitative RT-PCR assays for the most common KIAA1549-BRAF fusion transcripts. Application of these assays to a collection of 51 low-grade pediatric gliomas showed 97% sensitivity and 91% specificity compared with fluorescence in situ hybridization or array comparative genomic hybridization. In parallel, we assayed samples for the presence of the BRAF V600E mutation by PCR pyrosequencing. The data further support previous observations that these two alterations of the BRAF, KIAA1549 fusions and V600E point mutations, are associated primarily with pilocytic astrocytomas and nonpilocytic gliomas, respectively. These results show that fusion transcripts and mutations can be detected reliably in standard FFPE specimens and may be useful for incorporation into future studies of pediatric gliomas in basic science or clinical trials. PMID:21884820

  20. Case Report: A Rosette-forming Glioneuronal Tumor in the Tectal Plate in a Patient with Neurofibromatosis Type I

    PubMed Central

    Payne, Russell; Langan, Sara; Specht, Charles S

    2016-01-01

    We report the case of a 41–year-old female with neurofibromatosis Type 1 (NF1) who developed a rosette-forming glioneuronal tumor (RGNT) in the tectal plate. This tumor was diagnosed in 2002 when the patient presented with obstructive hydrocephalus, which was subsequently treated with a ventriculoperitoneal shunt and then an endoscopic third ventriculostomy. Initially thought to be a pilocytic astrocytoma, it was followed with serial magnetic resonance imaging (MRI) until tumor progression and development of a large fourth ventricular cystic component prompted resection via suboccipital craniotomy. Histological examination demonstrated an RGNT, a WHO Grade 1 tumor, with neurocytic rosettes, perivascular pseudorosettes, and elements resembling a pilocytic astrocytoma. Initially, the patient did well after her craniotomy, but postoperative complications set in that eventually led to her death. In this case report, we describe a relatively rare tumor that, despite its benign nature, leads to frequent complications and deficits due to its surgically challenging location. Along with previously reported examples, this cases raises the possibility of a causal relationship between NF1 and RGNT.  PMID:27917325

  1. The diagnostic accuracy of multiparametric MRI to determine pediatric brain tumor grades and types.

    PubMed

    Koob, Mériam; Girard, Nadine; Ghattas, Badih; Fellah, Slim; Confort-Gouny, Sylviane; Figarella-Branger, Dominique; Scavarda, Didier

    2016-04-01

    Childhood brain tumors show great histological variability. The goal of this retrospective study was to assess the diagnostic accuracy of multimodal MR imaging (diffusion, perfusion, MR spectroscopy) in the distinction of pediatric brain tumor grades and types. Seventy-six patients (range 1 month to 18 years) with brain tumors underwent multimodal MR imaging. Tumors were categorized by grade (I-IV) and by histological type (A-H). Multivariate statistical analysis was performed to evaluate the diagnostic accuracy of single and combined MR modalities, and of single imaging parameters to distinguish the different groups. The highest diagnostic accuracy for tumor grading was obtained with diffusion-perfusion (73.24%) and for tumor typing with diffusion-perfusion-MR spectroscopy (55.76%). The best diagnostic accuracy was obtained for tumor grading in I and IV and for tumor typing in embryonal tumor and pilocytic astrocytoma. Poor accuracy was seen in other grades and types. ADC and rADC were the best parameters for tumor grading and typing followed by choline level with an intermediate echo time, CBV for grading and Tmax for typing. Multiparametric MR imaging can be accurate in determining tumor grades (primarily grades I and IV) and types (mainly pilocytic astrocytomas and embryonal tumors) in children.

  2. Dehydration in the Older Adult.

    PubMed

    Miller, Hayley J

    2015-09-01

    Dehydration affects 20% to 30% of older adults. It has a greater negative outcome in this population than in younger adults and increases mortality, morbidity, and disability. Dehydration is often caused by water deprivation in older adults, although excess water loss may also be a cause. Traditional markers for dehydration do not take into consideration many of the physiological differences present in older adults. Clinical assessment of dehydration in older adults poses different findings, yet is not always diagnostic. Treatment of dehydration should focus on prevention and early diagnosis before it negatively effects health and gives rise to comorbidities. The current article discusses what has most thoroughly been studied; the best strategies and assessment tools for evaluation, diagnosis, and treatment of dehydration in older adults; and what needs to be researched further. [Journal of Gerontological Nursing, 41(9), 8-13.].

  3. Coeliac disease in adults.

    PubMed

    Corazza, G R; Gasbarrini, G

    1995-06-01

    Coeliac disease is a chronic disease characterized by small bowel villous atrophy which impairs nutrient absorption and improves on withdrawal of wheat gliadins and barley, rye and oat prolamins from the diet. Knowledge of the adult form of coeliac disease has greatly improved in recent years. Although this knowledge is not yet sufficiently widespread among referring clinicians, it has, over the past few years, allowed an increasing number of patients to be diagnosed with subclinical forms characterized by minor, transient or apparently unrelated symptoms. As a consequence, our views on the clinical and epidemiological aspects of this condition, the prevalence of which in the general population is believed to be close to 1 in 300, have changed and are still changing. Since it has been demonstrated that a strict gluten-free diet is protective against the complications of adult coeliac disease, it is important that even subclinical and silent forms are diagnosed and treated as early as possible. Non-invasive screening tests, such as anti-gliadin and anti-endomysium antibody estimation, should therefore be used systematically in groups considered to be at risk of coeliac disease. These include first-degree relatives of coeliac patients and patients with insulin-dependent diabetes mellitus, iron-deficiency anaemia, epilepsy with cerebral calcification, recurrent aphthous stomatitis and dental enamel hypoplasia. Other conditions will probably be identified in the near future.

  4. Human metapneumovirus in adults.

    PubMed

    Haas, Lenneke E M; Thijsen, Steven F T; van Elden, Leontine; Heemstra, Karen A

    2013-01-08

    Human metapneumovirus (HMPV) is a relative newly described virus. It was first isolated in 2001 and currently appears to be one of the most significant and common human viral infections. Retrospective serologic studies demonstrated the presence of HMPV antibodies in humans more than 50 years earlier. Although the virus was primarily known as causative agent of respiratory tract infections in children, HMPV is an important cause of respiratory infections in adults as well. Almost all children are infected by HMPV below the age of five; the repeated infections throughout life indicate transient immunity. HMPV infections usually are mild and self-limiting, but in the frail elderly and the immunocompromised patients, the clinical course can be complicated. Since culturing the virus is relatively difficult, diagnosis is mostly based on a nucleic acid amplification test, such as reverse transcriptase polymerase chain reaction. To date, no vaccine is available and treatment is supportive. However, ongoing research shows encouraging results. The aim of this paper is to review the current literature concerning HMPV infections in adults, and discuss recent development in treatment and vaccination.

  5. Sexting among young adults

    PubMed Central

    Gordon-Messer, Deborah; Bauermeister, Jose Arturo; Grodzinski, Alison; Zimmerman, Marc

    2012-01-01

    Purpose Sexting has stirred debate over its legality and safety, but few researchers have documented the relationship between sexting and health. We describe the sexting behavior of young adults in the United States, and examine its association with sexual behavior and psychological well-being. Methods Using an adapted web version of Respondent-Driven Sampling (webRDS) we recruited a sample of U.S. young adults (ages 18 to 24; N=3447). We examined participant sexting behavior using 4 categories of sexting: 1) Non-Sexters, 2) Receivers, 3) Senders, and 4) Two-way Sexters. We then assessed the relationships between sexting categories and sociodemographic characteristics, sexual behavior and psychological well-being. Results Over half (57%) of respondents were Non-Sexters, 28.2% of the sample were Two-way Sexters, 12.6% were Receivers, and 2% were Senders. Males were more likely to be Receivers than females. Sexually active respondents were more likely to be Two-way Sexters than non-sexually active respondents. Among participants who were sexually active in the past 30 days, we found no differences across sexting groups in number of sexual partners, or number of unprotected sex partners in the past 30 days. We also found no relationship between sexting and psychological well-being. Conclusions Our results suggest that sexting is not related to sexual risk behavior or psychological well-being. We discuss the findings of this study and propose directions for further research on sexting. PMID:23299018

  6. Adult Acute Leukaemia

    PubMed Central

    Atkinson, K.; Wells, D. G.; Clink, H. McD.; Kay, H. E. M.; Powles, R.; McElwain, T. J.

    1974-01-01

    Seventy-eight adult patients with acute leukaemia were classified cytologically into 3 categories: acute lymphoblastic leukaemia (ALL), acute myelogenous leukaemia (AML) or acute undifferentiated leukaemia (AUL). The periodic acid-Schiff stain was of little value in differentiating the 3 groups. The treatment response in each group was different: 94% of patients with ALL (16/17) achieved complete remission with prednisone, vincristine and other drugs in standard use in childhood ALL; 59% of patients with AML (27/46) achieved complete remission with cytosine arabinoside and daunorubicin (22 patients), or 6-thioguanine and cyclophosphamide (2 patients), 6-thioguanine, cyclophosphamide and Adriamycin (1 patient), and cytosine and Adriamycin (1 patient); only 2 out of 14 patients (14%) with acute undifferentiated leukaemia achieved complete remission using cytosine and daunorubicin after an initial trial of prednisone and vincristine had failed. Prednisone and vincristine would seem to be of no value in acute undifferentiated leukaemia. It would seem also that no benefit is obtained by classifying all patients with acute leukaemia over 20 years of age as “adult acute leukaemia” and treating them with the same polypharmaceutical regimen. The problems posed by each disease are different and such a policy serves only to obscure them. ImagesFig. 1Fig. 2Fig. 3 PMID:4141625

  7. Human Metapneumovirus in Adults

    PubMed Central

    Haas, Lenneke E. M.; Thijsen, Steven F. T.; van Elden, Leontine; Heemstra, Karen A.

    2013-01-01

    Human metapneumovirus (HMPV) is a relative newly described virus. It was first isolated in 2001 and currently appears to be one of the most significant and common human viral infections. Retrospective serologic studies demonstrated the presence of HMPV antibodies in humans more than 50 years earlier. Although the virus was primarily known as causative agent of respiratory tract infections in children, HMPV is an important cause of respiratory infections in adults as well. Almost all children are infected by HMPV below the age of five; the repeated infections throughout life indicate transient immunity. HMPV infections usually are mild and self-limiting, but in the frail elderly and the immunocompromised patients, the clinical course can be complicated. Since culturing the virus is relatively difficult, diagnosis is mostly based on a nucleic acid amplification test, such as reverse transcriptase polymerase chain reaction. To date, no vaccine is available and treatment is supportive. However, ongoing research shows encouraging results. The aim of this paper is to review the current literature concerning HMPV infections in adults, and discuss recent development in treatment and vaccination. PMID:23299785

  8. Fecal incontinence in older adults.

    PubMed

    Tariq, Syed H

    2007-11-01

    Fecal incontinence is an underreported and underappreciated problem in older adults. Although fecal incontinence is more common in women than in men, this difference narrows with aging. Risk factors that lead to the development of fecal incontinence include dementia, physical disability, and fecal impaction. Treatment options include medical or conservative therapy for older adults who have mild incontinence, and surgical options can be explored in selected older adults if surgical expertise is available.

  9. The Varieties of Adult Civic Engagement in Adult Learning

    ERIC Educational Resources Information Center

    Munoz, Linda; Wrigley, Heide Spruck

    2012-01-01

    Civic engagement, or the practice of democratic deliberation in adult education and learning, asks that adults use their experiences to cooperatively build solutions to the difficult social, economic, and political problems that affect their lives and communities now and into the future. The articles presented in this issue look at the…

  10. Responding to Young Adult Literature. Young Adult Literature Series.

    ERIC Educational Resources Information Center

    Monseau, Virginia R.

    This book focuses on how readers respond to the power of young adult literature--negating the assumption that because such literature appeals to adolescents it cannot possibly be worthy of a place in the language arts curriculum. The book serves two purposes: it describes and discusses the oral and written response of adolescents and adults to…

  11. Impact of Authentic Adult Literacy Instruction on Adult Literacy Practices.

    ERIC Educational Resources Information Center

    Purcell-Gates, Victoria; Degener, Sophie C.; Jacobson, Erik; Soler, Marta

    2002-01-01

    Investigates relationships between two dimensions of adult literacy instruction and change in the literacy practices of adult literacy students. Finds that authenticity of class literacy activities and texts had a statistically significant effect on change in student literacy practices; and increases in types of texts involved reading and writing…

  12. Young Adult Literature for Less Able Adult Readers.

    ERIC Educational Resources Information Center

    Radebaugh, Muriel Rogie

    1982-01-01

    Presents an annotated bibliography of 20 recent young adult novels that are also appropriate for use with adult readers in community college reading programs. Suggests ways of helping such students improve their reading comprehension by analyzing the novels' themes, conflicts, settings, characterization, and symbolism. (AEA)

  13. Adult Literacy and Numeracy: Assessing Change. Adult Literacy Research Network.

    ERIC Educational Resources Information Center

    Cumming, J. Joy, Ed.; van Kraayenoord, Christina E., Ed.

    This document contains eight papers from an action research program to foster good practice in adult literacy provision and policy. "Introduction" (J. Joy Cumming, Christina E. van Kraayenoord) presents an overview of the action research project and individual reports. "Assessment: Making a Difference in Adult Literacy and Numeracy…

  14. Oakland Adult Reading Lab. Building Comprehension in Adult Education Students.

    ERIC Educational Resources Information Center

    Johnston, Suzanne

    Many adult poor readers do not organize what they read in a way that best facilitates good comprehension. To help students overcome this problem, the Adult Day and Evening School in Oakland, California, organized a reading laboratory for their mostly low-income, educationally disadvantaged students with a diverse range of needs. Instruction in the…

  15. Adult Education in Australia: The Council of Adult Education.

    ERIC Educational Resources Information Center

    Randell, Shirley

    Liberal adult education in Victoria, Australia, takes its ideals, if not its form, from the pre-war university and Workers Education Association (WEA) partnerships: the university providing tutors and content, the WEA providing contact with unions and workers. Unique to Victoria is the level to which community-based adult education has been…

  16. Atomoxetine Treatment for ADHD: Younger Adults Compared with Older Adults

    ERIC Educational Resources Information Center

    Durell, Todd; Adler, Lenard; Wilens, Timothy; Paczkowski, Martin; Schuh, Kory

    2010-01-01

    Objective: Atomoxetine is a nonstimulant medication for treating child, adolescent, and adult ADHD. This meta-analysis compared the effects in younger and older adults. Method: A post hoc analysis was conducted using data from two double-blind, placebo-controlled clinical trials. Data from patients aged 18-25 years were compared with data from…

  17. Evaluation of Adult Education Programs. California Adult Education.

    ERIC Educational Resources Information Center

    California State Dept. of Education, Sacramento.

    To assist adult educators in finding meaningful ways to measure the effectiveness of instruction, this monograph provides selected illustrations of specific methods used by adult education instructors to verify student learning. Obtained from teachers in the field, the examples are from programs in (1) dental assisting, (2) instrument pilot ground…

  18. Building Resilience: Helping Young Adults in the Adult Education Classroom.

    ERIC Educational Resources Information Center

    Robinson, Elly

    2000-01-01

    Because of changes in welfare eligibility, the education system, and employment and training opportunities, it has become more likely that young people who have had difficulty with the mainstream schooling system and who face a lack of employment options will end up in adult education. Educators in the adult education classroom have an opportunity…

  19. [Hemolytic anemias in adults].

    PubMed

    Müller, A; Zimmermann, R; Krause, S W

    2011-11-01

    The erythrocyte lifespan in haemolytic anemia is shortened while erythropoesis is increased. Important labaratory findings are increased reticulocytes, LDH, indirect bilirubin and a decreased haptoglobin level. The most important diagnostic tool for further work up of hemolytic anemia is the direct antiglobulin test (DAT, Coombs test) to differentiate autoimmune hemolytic anemia (AIHA) from other causes. Another important group are fragmentation syndroms (hemolytic uremic syndrome and thrombotic thrombocytopenic purpura). In these forms of haemolytic anemia fragmented red blood cells can be found in the blood smear together with thrombocytopenia. A severe problem in paroxysmal nocturnal hematuria is the incidence of thrombosis. The following review describes the most important forms of hemolytic anemia in the adult and the diagnostic and therapeutic strategies.

  20. [Cochlear implant in adults].

    PubMed

    Bouccara, D; Mosnier, I; Bernardeschi, D; Ferrary, E; Sterkers, O

    2012-03-01

    Cochlear implant in adults is a procedure, dedicated to rehabilitate severe to profound hearing loss. Because of technological progresses and their applications for signal strategies, new devices can improve hearing, even in noise conditions. Binaural stimulation, cochlear implant and hearing aid or bilateral cochlear implants are the best opportunities to access to better level of comprehension in all conditions and space localisation. By now minimally invasive surgery is possible to preserve residual hearing and use a double stimulation modality for the same ear: electrical for high frequencies and acoustic for low frequencies. In several conditions, cochlear implant is not possible due to cochlear nerve tumour or major malformations of the inner ear. In these cases, a brainstem implantation can be considered. Clinical data demonstrate that improvement in daily communication, for both cochlear and brainstem implants, is correlated with cerebral activation of auditory cortex.

  1. Adult feminine hygiene practices.

    PubMed

    Czerwinski, B S

    1996-08-01

    Adult feminine hygiene practices are the focus of this exploratory descriptive study. In a sample of 193 women, the typical respondent lived in the Southeast and was a single student who was 23 years of age, and White. Body cleansing, feminine hygiene, and menses management practices were examined. It was found that handwashing varied according to bodily involvement or specific feminine hygiene practices. Assorted menses management products were used for menses management and were used when the woman was not menstruating. The results of this study suggest that it might be possible for health care providers to teach women safe and economical health care practices, such as not douching and handwashing before and after use of menses management products to prevent infections.

  2. Secondary hypertension in adults

    PubMed Central

    Puar, Troy Hai Kiat; Mok, Yingjuan; Debajyoti, Roy; Khoo, Joan; How, Choon How; Ng, Alvin Kok Heong

    2016-01-01

    Secondary hypertension occurs in a significant proportion of adult patients (~10%). In young patients, renal causes (glomerulonephritis) and coarctation of the aorta should be considered. In older patients, primary aldosteronism, obstructive sleep apnoea and renal artery stenosis are more prevalent than previously thought. Primary aldosteronism can be screened by taking morning aldosterone and renin levels, and should be considered in patients with severe, resistant or hypokalaemia-associated hypertension. Symptoms of obstructive sleep apnoea should be sought. Worsening of renal function after starting an angiotensin-converting enzyme inhibitor suggests the possibility of renal artery stenosis. Recognition, diagnosis and treatment of secondary causes of hypertension lead to good clinical outcomes and the possible reversal of end-organ damage, in addition to blood pressure control. As most patients with hypertension are managed at the primary care level, it is important for primary care physicians to recognise these conditions and refer patients appropriately. PMID:27211205

  3. [Vesicoureteral reflux in adults].

    PubMed

    Rollino, Cristiana; D'Urso, Leonardo; Beltrame, Giulietta; Ferro, Michela; Quattrocchio, Giacomo; Quarello, Francesco

    2011-01-01

    Vesicoureteral reflux (VUR) may be congenital or acquired. The most frequent form of congenital VUR is primary VUR. Its prevalence in adults is not exactly known, but it is higher in women, whose greater propensity for urinary tract infections increases the likelihood of an instrumental examination leading to the diagnosis of less severe cases. In men, even severe VUR may go undiagnosed for a long time. Primary VUR is due to a defect in the valve mechanism of the ureterovesical junction. In physiological conditions, the terminal ureter enters the bladder wall obliquely and bladder contraction leads to compression of this intravesical portion. Abnormal length of the intravesical portion of the ureter due to a genetic mutation (whose location is yet to be established) leads to VUR. In its less severe forms VUR may be asymptomatic, but in 50-70% of cases it manifests with recurrent cystitis or pyelonephritis. The manifestations leading to a diagnosis of VUR in adults, besides urinary tract infections, are proteinuria, renal failure and hypertension. The gold-standard diagnostic examination is a micturating cystourethrogram. Reflux nephropathy develops as a result of a pathogenetic mechanism unrelated to high cavity pressure or urinary tract infections but due to reduced formation of the normal renal parenchyma (hypoplasia or dysplasia). Abnormal renal parenchyma development is attributable to the same genes that control the development of the ureters and ureterovesical junction. VUR is considered only a marker of this abnormal development, playing no role in scar formation. There is no conclusive evidence regarding the indications for VUR correction. However, the risk that VUR leads to recurrent pyelonephritis and reflux nephropathy must be kept in mind. VUR certainly has to be corrected in women who contemplate pregnancy.

  4. An overview of adult-learning processes.

    PubMed

    Russell, Sally S

    2006-10-01

    Part of being an effective instructor involves understanding how adults learn best. Theories of adult education are based on valuing the prior learning and experience of adults. Adult learners have different learning styles which must be assessed prior to initiating any educational session. Health care providers can maximize teaching moments by incorporating specific adult-learning principles and learning styles into their teaching strategies.

  5. Native American Adult Reader I.

    ERIC Educational Resources Information Center

    King, Lovern Root, Ed.

    Aspects of Native American history and culture as well as issues and concerns of American Indians are presented in the twelve short articles in this reader for adults. Intended for use in an adult basic education/GED program, the reader features simply written stories (for grades 0-3), illustrations, vocabulary lists and student study questions.…

  6. Perceived Stress among Deaf Adults

    ERIC Educational Resources Information Center

    Jones, Elaine G.; Ouellette, Sue E.; Kang, Youngmi

    2006-01-01

    The Present Article describes the effectiveness of stress management classes in decreasing perceived stress among Deaf adults. Deaf adults may experience unique stressors, in addition to circumstances associated with increased stress in the general population. The Perceived Stress Scale (S. Cohen, Kamarck, & Mermelstein, 1983) was used as a…

  7. Senior Adult Consumer Advisory Manual,

    ERIC Educational Resources Information Center

    Ater, E. Carolyn, Ed.

    This manual is intended for use by senior adult peer advisors (age 60 and over) engaged in helping relationships in providing consumer education to other senior adults. The advisory procedures are based on a problem solving approach which incorporates the development of a self-help concept. Chapter 1 provides information on consumer advising. It…

  8. Adult Academy Tutor Training Manual.

    ERIC Educational Resources Information Center

    Isserlis, Janet; And Others

    This handbook is for volunteer tutors, student interns, and VISTA volunteers working with adult basic education (ABE) and English-as-a-Second-Language (ESL) learners. The community-based handbook contains information about adult literacy and tutoring--what tutors do, who the learners are, and how the literacy learning process works. Introductory…

  9. Adult Education at a Distance.

    ERIC Educational Resources Information Center

    Gaudet, Alphonse

    This document, which examines the use of educational technologies for distance education for adults in Canada, consists of five narrative sections and a bibliography. The first section introduces the topic and the document's objectives (to describe those technologies used in Canadian adult distance education, paying particular attention to those…

  10. Segmenting the Adult Education Market.

    ERIC Educational Resources Information Center

    Aurand, Tim

    1994-01-01

    Describes market segmentation and how the principles of segmentation can be applied to the adult education market. Indicates that applying segmentation techniques to adult education programs results in programs that are educationally and financially satisfying and serve an appropriate population. (JOW)

  11. Women, Class and Adult Education.

    ERIC Educational Resources Information Center

    Southampton Univ. (England).

    This collection of working papers deals with the relationship among women, social class, and adult education. In her paper entitled "Women and University Extension," Pat Usher argues that by sustaining the dominant cultural, ideological, and social relationships of production in capitalist Britain, university adult education contributes…

  12. Book Display as Adult Service.

    ERIC Educational Resources Information Center

    Moore, Matthew S.

    1997-01-01

    Defines book display as an adult service as choosing and positioning adult books from the library collection to increase their circulation. The author contrasts bookstore arrangement for sales versus library arrangement for access, including contrasting missions, genre grouping, weeding, problems, and dimensions. (Author/LRW)

  13. Journey to International Adult Education

    ERIC Educational Resources Information Center

    Sun, Qi

    2005-01-01

    In this article, the author describes her journey to international adult education and shares some lessons learned from her journey. The author developed her interest in international adult education through the Scientific Research Institute of International and Comparative Education (SRIICE) at Beijing Normal University and discovered its…

  14. Curriculum Models in Adult Education.

    ERIC Educational Resources Information Center

    Langenbach, Michael

    This book describes several curriculum models currently used in the field of adult education in an effort to assist adult educators who develop curricula as a routine part of their jobs. The book is divided into 14 chapters that are grouped into 7 sections. Each section covers a type of educational program, and each chapter describes a specific…

  15. The Politics of Adult Education

    ERIC Educational Resources Information Center

    Ellison, Art

    2016-01-01

    Art Ellison is longtime advocate for adult education, having managed numerous advocacy campaigns over the past forty years on the state and national levels. Prior to his employment in 1980 as the NH State Director of Adult Education he worked for many years as a high school teacher and as a community organizer. In this article, Ellison offers some…

  16. Re-thinking Adult Literacy.

    ERIC Educational Resources Information Center

    Draper, James A.

    A study was conducted to examine the literature on literacy and adult basic education and to identify various issues, trends, problems, possible solutions, and basic principles that might guide programs and policies in adult literacy and basic education in Canada. More than 120 documents were examined, raising such issues as what is literacy and…

  17. ESOL and the Adult Learner.

    ERIC Educational Resources Information Center

    Regan, Timothy F.

    Problems of adult basic education in the United States, symptomatic of the connection between poverty, poor education, and unemployment, have forged for the disadvantaged adult most of the links in the unbreakable chain of deprivation, frustration, and despair. The problem of ESOL (English for Speakers of Other Languages) instruction is…

  18. Cultural Influences on Adult Learning.

    ERIC Educational Resources Information Center

    Conti, Gary J., Ed.; Fellenz, Robert A., Ed.

    Five projects are reported that examined factors related to adult learning in nontraditional environments. "Conrad, Montana: A Community of Memories" (Janice Counter, Lynn Paul, and Gary Conti) reports on a group of adults who for over 40 years have been active in building a better community for friends, relatives, and themselves. A…

  19. Adult Learning Opportunities in Nepal

    ERIC Educational Resources Information Center

    Regmi, Krishna; Regmi, Sharada

    2008-01-01

    This paper presents the initial findings from a study of education system in Nepal. This paper examines the adult learning opportunities within the educational and cultural contexts by reviewing available literature relevant to Nepal. Findings show that there are wider opportunities for adult learning than those considered from education and…

  20. Creating Adult Basic Education Programs.

    ERIC Educational Resources Information Center

    Harris, Dolores M.

    Adult basic education programs must teach the "social living skills" disadvantaged adults need, as well as basic literacy skills. In creating an ABE program, one must first assess the needs of the target population--through surveys, group meetings, an advisory council of members of the target population, demographic studies, and consideration of…

  1. Neuropsychological Assessment of Adult Offenders

    ERIC Educational Resources Information Center

    Marceau, Roger; Meghani, Rehana; Reddon, John R.

    2008-01-01

    This report is primarily concerned with reporting on the normative results obtained on a large sample of serious adult offenders. An expanded Halstead-Reitan Neuropsychological Test Battery was administered to 584 adult offenders (OF), 132 normal controls (NC), and 494 acute psychiatric patients (PP). Subjects were between 18 and 44 years of age.…

  2. Examining Controversies in Adult Education.

    ERIC Educational Resources Information Center

    Kreitlow, Burton W.; And Others

    Controversies over adult education purposes, methods, audiences, and procedures are examined. After outlining a procedure for reviewing competing positions on controversial topics, the book pairs the contrasting views of two authors on each of 10 key issues facing adult education. Chapters cover: philosophies at issue (David L. Boggs); identifying…

  3. Predictive Modeling in Adult Education

    ERIC Educational Resources Information Center

    Lindner, Charles L.

    2011-01-01

    The current economic crisis, a growing workforce, the increasing lifespan of workers, and demanding, complex jobs have made organizations highly selective in employee recruitment and retention. It is therefore important, to the adult educator, to develop models of learning that better prepare adult learners for the workplace. The purpose of…

  4. Travel and Adult Transformative Learning

    ERIC Educational Resources Information Center

    Lindstrom, Steven K.

    2011-01-01

    This phenomenological research study examines the lived experience of individual adult transformation in the context of travel. Adults throughout history have experienced profound personal and perception changes as a result of significant travel events. Transformative learning occurs through experience, crisis, and reflection, all of which are…

  5. Adult Transition Program without Walls

    ERIC Educational Resources Information Center

    Moberg, Eric

    2010-01-01

    Best practices in adult transition special education for moderate to severe students suggest student-centered planning that maximizes independence in adult life. Based on the above sources, school districts and governing boards would best serve moderate to severe transition special education students with increasing integration into the community…

  6. Assessment Models for Adult Education.

    ERIC Educational Resources Information Center

    Snow, Ellen; And Others

    This handbook was developed to provide adult educators in Texas with sufficient background in assessment models to ensure confidence in recognizing and/or selecting appropriate measurement techniques and in using evaluation results to individualize and improve instruction for adult students. The handbook is based on information derived from a…

  7. Literature for Today's Young Adults.

    ERIC Educational Resources Information Center

    Donelson, Kenneth L.; Nilsen, Alleen Pace

    Defining young adult literature to include any book freely chosen for reading by a person between the ages of 12 and 20, this book is intended to help educate professionals in related fields about the growing body of such literature. The first section of the book provides an introduction to young adult literature, including a discussion of the…

  8. The History of Adult Education.

    ERIC Educational Resources Information Center

    Hudson, J. W.

    Beginning with such movements as the eighteenth century moral reformation societies and Welsh Sunday schools, and the first adult schools for both men and women in the early 1800's, this historical review traces British adult education up to 1850. Emphasis is on the extensive and widespread programs of the Mechanics' (workingmen's) Institutes and…

  9. Adult Functional Competency: A Summary.

    ERIC Educational Resources Information Center

    Texas Univ., Austin. Div. of Extension.

    The Adult Performance Level (APL) project summary specifies the competencies which are functional to economic and educational success in society and describes devices developed for assessing those competencies. The APL theory of functional competency identifies adult needs in general knowledge areas (consumer economics, occupational knowledge,…

  10. Adult Education in India & Abroad.

    ERIC Educational Resources Information Center

    Roy, Nikhil Ranjan

    A survey is made of various aspects of adult education in India since 1947, together with comparative accounts of the origin, development, and notable features of adult education in Denmark, Great Britain, the Soviet Union, and the United States. Needs and objectives in India, largely in the eradication of illiteracy, are set forth, and pertinent…

  11. Recruiting and Retaining Adult Students.

    ERIC Educational Resources Information Center

    Hadfield, Janice

    2003-01-01

    Adult learners, long the stepchildren of colleges and universities, have nearly become the norm, and they spend billions of dollars each year on education. This chapter takes a customer-oriented approach to recruiting and retaining adult students in higher education. (GCP)

  12. Understanding Adult Education and Training.

    ERIC Educational Resources Information Center

    Foley, Griff, Ed.

    This book introduces readers to issues, debates and literatures related to a number of central areas of practice in adult education and training, especially in Australia. It is intended as a first attempt to define the field of adult education in Australia in an analytical and theoretical, as opposed to a theoretical and practical sense. Written…

  13. Adult Learning Disorders: Contemporary Issues

    ERIC Educational Resources Information Center

    Wolf, Lorraine E., Ed.; Schreiber, Hope E., Ed.; Wasserstein, Jeanette, Ed.

    2008-01-01

    Recent advances in neuroimaging and genetics technologies have enhanced our understanding of neurodevelopmental disorders in adults. The authors in this volume not only discuss such advances as they apply to adults with learning disorders, but also address their translation into clinical practice. One cluster of chapters addresses developmental…

  14. Sibling Status Effects: Adult Expectations.

    ERIC Educational Resources Information Center

    Baskett, Linda Musun

    1985-01-01

    This study attempted to determine what expectations or beliefs adults might hold about a child based on his or her sibling status alone. Ratings on 50 adjective pairs for each of three sibling status types, only, oldest, and youngest child, were assessed in relation to adult expectations, birth order, and parental status of rater. (Author/DST)

  15. Books for Adult New Readers.

    ERIC Educational Resources Information Center

    O'Brien, Roberta Luther, Comp.

    This document is an annotated bibliography of recommended print materials for English-speaking adults reading at the seventh grade level or below. (Sixty percent of the titles are at fifth grade level or below). The titles were selected for their broad appeal to the average adult new reader. In the selection, special consideration was given to…

  16. Adult Learners in the Academy

    ERIC Educational Resources Information Center

    Bash, Lee

    1999-01-01

    Adult learners comprise almost 50 percent of all students enrolled in higher Education. Some argue they are pioneering change in today's higher educational landscape. This book is designed to assist faculty members and administrators who want to understand how the impact of adult learning programs has and is helping to transform the academy and…

  17. Adult Learners in the Academy.

    ERIC Educational Resources Information Center

    Bash, Lee

    Adult learning programs are becoming increasingly important. This book is designed to serve as a wake-up call for members of the academy who prefer to work with traditional students. It provides practical advice for adult learning programs with insights drawn from case studies and the author's experience. Part 1, "Context and Overview," contains:…

  18. Research Perspectives in Adult Education.

    ERIC Educational Resources Information Center

    Garrison, D. Randy, Ed.

    This book focuses on understanding the epistemological foundation of adult education, the research process, policy issues, and directions for the future. "An Epistemological Overview of the Field" (Garrison) provides an overview of adult education research: the historical development, issues, the scope of the knowledge base, and approaches to…

  19. Clinical Interviewing with Older Adults

    ERIC Educational Resources Information Center

    Mohlman, Jan; Sirota, Karen Gainer; Papp, Laszlo A.; Staples, Alison M.; King, Arlene; Gorenstein, Ethan E.

    2012-01-01

    Over the next few decades the older adult population will increase dramatically, and prevalence rates of psychiatric disorders are also expected to increase in the elderly cohort. These demographic projections highlight the need for diagnostic instruments and methods that are specifically tailored to older adults. The current paper discusses the…

  20. Adult attachment and declining birthrates.

    PubMed

    Draper, Thomas W; Holman, Thomas B; White, Whitney; Grandy, Shannon

    2007-02-01

    Attachment scores for 658 young adults living in the U.S.A. were obtained using the Experiences in Close Relationships scale. The participants came from a subsample of the RELATE data set, who had also filled out the adult attachment measure. Those young adults living in Utah County, Utah, an area of the country with a higher than normal birthrate (88% members of the Church of Jesus Christ of Latter-day Saints), also had higher than average adult attachment scores. While the methodology was not sufficient to assess causal direction nor eliminate the possibility of unidentified influences, an undiscussed psychological factor, adult attachment, may play a role in the numerical declines observed among nonimmigrant communities in the USA and Europe.

  1. Just How Adult Is This Young Adult Book: Young Adult Books for the Junior High Readers.

    ERIC Educational Resources Information Center

    Decker, Charlotte

    1999-01-01

    Discusses young adult novels and presents a bibliography to acquaint librarians with titles and authors that are suitable for emerging young adult readers in grades five through nine. Subject categories include realistic fiction, in the news, historical fiction, short stories, legendary characters, mysteries, science fiction/fantasy/horror, and…

  2. The day of your surgery - adult

    MedlinePlus

    Same-day surgery - adult; Ambulatory surgery - adult; Surgical procedure - adult; Preoperative care - day of surgery ... meet with them at an appointment before the day of surgery or on the same day of ...

  3. Coaching as a Strategy for Helping Adults

    ERIC Educational Resources Information Center

    Wax, Dorothy M.; Wertheim, Judith

    2015-01-01

    This chapter focuses on the use of coaching for adult learners, the specific characteristics adults bring to the learning environment, and strategies for dealing with the obstacles adult learners may face.

  4. The structure of adult ADHD.

    PubMed

    Adler, Lenard A; Faraone, Stephen V; Spencer, Thomas J; Berglund, Patricia; Alperin, Samuel; Kessler, Ronald C

    2017-03-01

    Although DSM-5 stipulates that symptoms of attention-deficit hyperactivity disorder (ADHD) are the same for adults as children, clinical observations suggest that adults have more diverse deficits than children in higher-level executive functioning and emotional control. Previous psychometric analyses to evaluate these observations have been limited in ways addressed in the current study, which analyzes the structure of an expanded set of adult ADHD symptoms in three pooled US samples: a national household sample, a sample of health plan members, and a sample of adults referred for evaluation at an adult ADHD clinic. Exploratory factor analysis found four factors representing executive dysfunction/inattention (including, but not limited to, all the DSM-5 inattentive symptoms, with non-DSM symptoms having factor loadings comparable to those of DSM symptoms), hyperactivity, impulsivity, and emotional dyscontrol. Empirically-derived multivariate symptom profiles were broadly consistent with the DSM-5 inattentive-only, hyperactive/impulsive-only, and combined presentations, but with inattention including executive dysfunction/inattention and hyperactivity-only limited to hyperactivity without high symptoms of impulsivity. These results show that executive dysfunction is as central as DSM-5 symptoms to adult ADHD, while emotional dyscontrol is more distinct but nonetheless part of the combined presentation of adult ADHD.

  5. Craniopharyngioma in Adults

    PubMed Central

    Zoicas, Flavius; Schöfl, Christof

    2012-01-01

    Craniopharyngiomas are slow growing benign tumors of the sellar and parasellar region with an overall incidence rate of approximately 1.3 per million. During adulthood there is a peak incidence between 40 and 44 years. There are two histopathological types, the adamantinomatous and the papillary type. The later type occurs almost exclusively in adult patients. The presenting symptoms develop over years and display a wide spectrum comprising visual, endocrine, hypothalamic, neurological, and neuropsychological manifestations. Currently, the main treatment option consists in surgical excision followed by radiation therapy in case of residual tumor. Whether gross total or partial resection should be preferred has to be balanced on an individual basis considering the extent of the tumor (e.g., hypothalamic invasion). Although the overall long-term survival is good it is often associated with substantial morbidity. Preexisting disorders are often permanent or even exacerbated by treatment. Endocrine disturbances need careful replacement and metabolic sequelae should be effectively treated. Regular follow-up by a multidisciplinary team is a prerequisite for optimal outcome of these patients. PMID:22654868

  6. Adult hereditary fructose intolerance.

    PubMed

    Yasawy, Mohamed Ismail; Folsch, Ulrich Richard; Schmidt, Wolfgang Eckhard; Schwend, Michael

    2009-05-21

    Hereditary fructose intolerance (HFI) is an under-recognized, preventable life-threatening condition. It is an autosomal recessive disorder with subnormal activity of aldolase B in the liver, kidney and small bowel. Symptoms are present only after the ingestion of fructose, which leads to brisk hypoglycemia, and an individual with continued ingestion will exhibit vomiting, abdominal pain, failure to thrive, and renal and liver failure. A diagnosis of HFI was made in a 50-year-old woman on the basis of medical history, response to IV fructose intolerance test, demonstration of aldolase B activity reduction in duodenal biopsy, and molecular analysis of leukocyte DNA by PCR showed homozygosity for two doses of mutant gene. HFI may remain undiagnosed until adult life and may lead to disastrous complications following inadvertent fructose or sorbitol infusion. Several lethal episodes of HFI following sorbitol and fructose infusion have been reported. The diagnosis can only be suspected by taking a careful dietary history, and this can present serious complications.

  7. Vitalistic thinking in adults.

    PubMed

    Wilson, Stuart

    2013-11-01

    Vitalistic thinking has traditionally been associated with reasoning about biological phenomena. The current research aimed to investigate a broader range of vitalistic thinking than previously studied. Esoteric notions of 'energy' are frequently used by individuals when making causal attributions for strange occurrences, and previous literature has linked such thinking with paranormal, magical, and superstitious beliefs. Two experiments are described that aim to investigate whether adults are vitalistic when asked to make causal judgments, and whether this can be predicted by thinking styles and prior paranormal belief. Experiment 1 asked participants to rate three causal options (one of which was vitalistic) for six vignettes. Scores on one dimension of paranormal belief (New Age Philosophy) and analytical thinking significantly predicted vitalism, but scores on intuitive thinking and Traditional Paranormal Beliefs did not. Experiment 2 extended the findings by asking participants to generate their own causal responses. Again, paranormal belief was found to be the best predictor of vitalism, but this time Traditional Paranormal Beliefs were associated with vitalistic responses whilst both intuitive and analytical thinking were unable to significantly predict classification. Results challenge previous findings, suggesting that vitalistic thinking may operate differently when applied to everyday causal reasoning.

  8. Occupation and adult gliomas.

    PubMed

    Carozza, S E; Wrensch, M; Miike, R; Newman, B; Olshan, A F; Savitz, D A; Yost, M; Lee, M

    2000-11-01

    Lifetime job histories from a population-based, case-control study of gliomas diagnosed among adults in the San Francisco Bay area between August 1991 and April 1994 were evaluated to assess occupational risk factors. Occupational data for 476 cases and 462 controls were analyzed, with adjustment for age, gender, education, and race. Imprecise increased risks were observed for physicians and surgeons (odds ratio (OR) = 3.5, 95% confidence interval (CI): 0.7, 17.6), artists (OR = 1.9, 95% CI: 0.5, 6.5), foundry and smelter workers (OR = 2.6, 95% CI: 0.5, 13.1), petroleum and gas workers (OR = 4.9, 95% CI: 0.6, 42.2), and painters (OR = 1.6, 95% CI: 0.5, 4.9). Legal and social service workers, shippers, janitors, motor vehicle operators, and aircraft operators had increased odds ratios only with longer duration of employment. Physicians and surgeons, foundry and smelter workers, petroleum and gas workers, and painters showed increased risk for both astrocytic and nonastrocytic tumors. Artists and firemen had increased risk for astrocytic tumors only, while messengers, textile workers, aircraft operators, and vehicle manufacturing workers showed increased risk only for nonastrocytic tumors. Despite study limitations, including small numbers for many of the occupational groups, a high percentage of proxy respondents among cases, and lack of specific exposure information, associations were observed for several occupations previously reported to be at higher risk for brain tumors generally and gliomas specifically.

  9. Clueless: Adult Mysteries with Young Adult Appeal 2002.

    ERIC Educational Resources Information Center

    Charles, John; Morrison, Joanna

    2002-01-01

    This annotated bibliography includes adult mysteries that appeal to teen readers under the categories of Sherlock Holmes; reference sources; private investigators; amateur sleuths; historical sleuths; suspense and thrillers; police procedurals; mystery blends; and anthologies. (LRW)

  10. Adult outcomes of preterm children.

    PubMed

    Hack, Maureen

    2009-10-01

    The survivors of the initial years of neonatal intensive care of preterm infants reached adulthood during the last decade. Reports of their adult outcomes examined have included neurodevelopmental, behavioral and health outcomes as well as social functioning and reproduction. Despite statistically significant differences between preterm young adults and controls in most outcomes studied, the majority of preterm survivors do well and live fairly normal lives. The two major predictors of adult outcomes are lower gestational age that reflect perinatal injury and family sociodemographic status which reflects both genetic and environmental effects.

  11. Computational models of adult neurogenesis

    NASA Astrophysics Data System (ADS)

    Cecchi, Guillermo A.; Magnasco, Marcelo O.

    2005-10-01

    Experimental results in recent years have shown that adult neurogenesis is a significant phenomenon in the mammalian brain. Little is known, however, about the functional role played by the generation and destruction of neurons in the context of an adult brain. Here, we propose two models where new projection neurons are incorporated. We show that in both models, using incorporation and removal of neurons as a computational tool, it is possible to achieve a higher computational efficiency that in purely static, synapse-learning-driven networks. We also discuss the implication for understanding the role of adult neurogenesis in specific brain areas like the olfactory bulb and the dentate gyrus.

  12. Nonverbal learning disability: adult outcomes.

    PubMed

    Dugbartey, A T

    2000-07-01

    There are few empirical studies of the adult outcomes of nonverbal learning disability (NLD). An overwhelming majority of NLD studies has been devoted to the nature of academic difficulties of school children, whereas the few follow-up studies have tended to be limited to college-age young adults. Herein, it is argued that the problems of adults with NLD do not fall solely in academic areas, and that early academic remediation programs might do well to include intervention in emotional and social skills enhancement.

  13. Adult Learners' Week in Australia.

    ERIC Educational Resources Information Center

    Cross, John

    2002-01-01

    Promotional materials and activities for Australia's Adult Learners Week, which are shaped by a variety of stakeholders , include media strategies and a website. Activities are evaluated using a market research company and website and telephone hotline statistics. (SK)

  14. Therapeutic Recreation and Adult Education.

    ERIC Educational Resources Information Center

    Jones, David

    1993-01-01

    Therapeutic recreation is a means of empowering individuals with disabilities through arts or sports. The field has developed differently in the United States and the United Kingdom; the former emphasizes professionalization and the latter the right to adult education. (SK)

  15. Interstitial lung disease - adults - discharge

    MedlinePlus

    ... lung disease Pulmonary alveolar proteinosis Rheumatoid lung disease Sarcoidosis Patient Instructions Eating extra calories when sick - adults ... team. Related MedlinePlus Health Topics Interstitial Lung Diseases Sarcoidosis Browse the Encyclopedia A.D.A.M., Inc. ...

  16. Vaccinations for Adults with Diabetes

    MedlinePlus

    Vaccinations for Adults with Diabetes The table below shows which vaccinations you should have to protect your health if ... sure you and your healthcare provider keep your vaccinations up to date. Vaccine Do you need it? ...

  17. Recommended Immunizations for Adults 50+

    MedlinePlus

    ... page please turn Javascript on. Health Screenings and Immunizations Recommended Immunizations For Adults 50+ The content in this section ... out more, visit How Vaccines Prevent Disease . Vaccines, Vaccinations, and Immunizations Understanding the difference between vaccines, vaccinations, ...

  18. Split liver transplantation in adults

    PubMed Central

    Hashimoto, Koji; Fujiki, Masato; Quintini, Cristiano; Aucejo, Federico N; Uso, Teresa Diago; Kelly, Dympna M; Eghtesad, Bijan; Fung, John J; Miller, Charles M

    2016-01-01

    Split liver transplantation (SLT), while widely accepted in pediatrics, remains underutilized in adults. Advancements in surgical techniques and donor-recipient matching, however, have allowed expansion of SLT from utilization of the right trisegment graft to now include use of the hemiliver graft as well. Despite less favorable outcomes in the early experience, better outcomes have been reported by experienced centers and have further validated the feasibility of SLT. Importantly, more than two decades of experience have identified key requirements for successful SLT in adults. When these requirements are met, SLT can achieve outcomes equivalent to those achieved with other types of liver transplantation for adults. However, substantial challenges, such as surgical techniques, logistics, and ethics, persist as ongoing barriers to further expansion of this highly complex procedure. This review outlines the current state of SLT in adults, focusing on donor and recipient selection based on physiology, surgical techniques, surgical outcomes, and ethical issues. PMID:27672272

  19. Adult Education and Public Policy

    ERIC Educational Resources Information Center

    Fay, Francis A.

    1972-01-01

    Author discussed American public's shifts in values and priorities" and suggests that adult educators become involved in 'real politique'" in order to help form public policy in the future. (Author/SP)

  20. Hip Fractures among Older Adults

    MedlinePlus

    ... training for health care providers. Learn More Hip Fractures Among Older Adults Recommend on Facebook Tweet Share ... older. What You Can Do to Prevent Hip Fractures You can prevent hip fractures by taking steps ...

  1. Collaborative Writing for Young Adults.

    ERIC Educational Resources Information Center

    Hadley, Lee; Irwin, Annabelle

    1992-01-01

    Presents a dialogue between the authors on what it is like to collaborate in writing young adult fiction. Discusses their writing processes, how they come up with ideas for their books, and how they get the books published. (RS)

  2. Diabetes: Unique to Older Adults

    MedlinePlus

    ... Stroke Urinary Incontinence Related Documents PDF Choosing Wisely: Diabetes Tests and Treatments Download Related Video Join our e-newsletter! Aging & Health A to Z Diabetes Unique to Older Adults This section provides information ...

  3. Youths Transitioning as Adult Learners

    ERIC Educational Resources Information Center

    Davis, C. Amelia

    2014-01-01

    This chapter considers how transitions to adulthood have been historically represented and presents alternative ways of thinking about transitions to adulthood through the context of adult basic education programs.

  4. Osteoporosis: Unique to Older Adults

    MedlinePlus

    ... of fractures if needed annual flu shots. Protein-Calorie Malnutrition Many older adults living at home eat ... so serious that a condition known as protein-calorie malnutrition (PCM) develops. Sometimes, PCM occurs after a ...

  5. Older Adults and Mental Health

    MedlinePlus

    ... and Resources Clinical Trials Share Older Adults and Mental Health Overview It’s just as important for an older ... this helpline, sponsored by the Substance Abuse and Mental Health Services Administration (SAMHSA), to receive immediate counseling. Calling ...

  6. Prosthetic aspects in adult osteopetrosis.

    PubMed

    Ogino, Yoichiro; Ayukawa, Yasunori; Tomita, Yoko; Koyano, Kiyoshi

    2014-10-01

    Osteopetrosis (OP) is a rare condition characterized by skeletal sclerosis caused by dysfunctional osteoclasts. Though many reports have described severe infantile-malignant autosomal recessive OP, few have described the prosthetic management of adult OP. This report discusses the prosthetic treatment of adult OP. Although prosthodontists should try to reconstruct occlusal function as much as possible, a conservative prosthodontic approach may be a reasonable and recommended treatment option for minimizing the risk of further osteomyelitis and osteonecrosis.

  7. Adult Learning Program Service (ALPS).

    ERIC Educational Resources Information Center

    Carlisle, Robert

    The Adult Learning Program Service (ALPS) aims to reach eight and a half million adults between ages 25 and 44 and teach them reading and math skills they can use at home and on the job. ALPS proposes to reach those who have never finished high school but do have at least a sixth-grade reading level. They could use their new skills to prepare for…

  8. A multivariate analysis of factors determining tumor progression in childhood low-grade glioma: a population-based cohort study (CCLG CNS9702)

    PubMed Central

    Stokland, Tore; Liu, Jo-Fen; Ironside, James W.; Ellison, David W.; Taylor, Roger; Robinson, Kathryn J.; Picton, Susan V.; Walker, David A.

    2010-01-01

    The purpose of this study was to identify risk factors for the progression of low-grade glioma in children from a large population-based cohort. Patient and tumor details of a national cohort of children with low-grade glioma, recruited into an international multidisciplinary clinical strategy, were subjected to univariate and multivariate analyses of progression-free survival and overall survival. From the cohort of 798 patients, 639 patients were eligible, with a median age 6.71 years (0.26–16.75 years); 49% were males; 15.9% had neurofibromatosis type 1, 63.7% pilocytic astrocytoma, 5.9% fibrillary astrocytoma, 4.2% mixed neuronal-glial tumors, and 3.6% others; 21.1% were diagnosed clinically. Anatomically implicated were 31.6% cerebellum, 24.6% chiasma/hypothalamus, 16.0% cerebral hemispheres, 9.9% brain stem, 6.1% other supratentorial midline structures, 5.9% optic nerve only, 4.5% spinal cord, and 1.4% others. The 5-year overall survival and progression-free survival in the whole cohort were 94.6% and 69.4%, respectively. There was a significant association between age and site (P < .001) and extent of tumor resection and site (P < .001). Multivariate analysis identified young age, fibrillary astrocytoma, and extent of surgical resection as significant independent risk factors for progression. Hypothalamic/chiasmatic tumors demonstrated the most sustained tendency to progress. In conclusion, the influence of age and anatomical site upon the risk of tumor progression suggests that these factors strongly influence tumor behavior for the majority of pilocytic tumors. Age <1 year and 1–5 years, fibrillary histology, completeness of resection, and chiasmatic location are candidates for stratification in future studies. PMID:20861086

  9. Severe sepsis in older adults.

    PubMed

    Umberger, Reba; Callen, Bonnie; Brown, Mary Lynn

    2015-01-01

    Severe sepsis may be underrecognized in older adults. Therefore, the purpose of this article is to review special considerations related to early detection of severe sepsis in older adults. Normal organ changes attributed to aging may delay early detection of sepsis at the time when interventions have the greatest potential to improve patient outcomes. Systems are reviewed for changes. For example, the cardiovascular system may have a limited or absent compensatory response to inflammation after an infectious insult, and the febrile response and recruitment of white blood cells may be blunted because of immunosenescence in aging. Three of the 4 hallmark responses (temperature, heart rate, and white blood cell count) to systemic inflammation may be diminished in older adults as compared with younger adults. It is important to consider that older adults may not always manifest the typical systemic inflammatory response syndrome. Atypical signs such as confusion, decreased appetite, and unsteady gait may occur before sepsis related organ failure. Systemic inflammatory response syndrome criteria and a comparison of organ failure criteria were reviewed. Mortality rates in sepsis and severe sepsis remain high and are often complicated by multiple organ failures. As the numbers of older adults increase, early identification and prompt treatment is crucial in improving patient outcomes.

  10. Anaphor Comprehension in Younger and Older Adults.

    ERIC Educational Resources Information Center

    Zelinski, Elizabeth M.; Miura, Shari A.

    1990-01-01

    Evaluated adult age differences in language comprehension with groups of young adults (age 20-35), young old adults (age 55-69), and old old adults (age 70-87). The results suggest that speed of comprehension processes required to match related terms in sentence pairs is not impaired with age as long as terms do not have to be remembered.…

  11. Adult Education and Development, No. 47.

    ERIC Educational Resources Information Center

    Adult Education and Development, 1996

    1996-01-01

    This serial issue contains a total of 26 articles grouped under five headings: "Adult Learning: A Key for the Twenty-First Century (Fifth International Conference on Adult Education (Confintea V))"; "Trends in Adult Education Policy" (Belanger); "Adult Education in Modern Times" (Geissler); "From Criticism to…

  12. Dealing with Disruptive Behavior of Adult Learners

    ERIC Educational Resources Information Center

    Dobmeier, Robert; Moran, Joseph

    2008-01-01

    The adult education literature on disruptive behavior of adult learners was reviewed and a survey on disruptive behavior of adult learners was conducted with adult educators. The findings are synthesized in a conceptual framework for understanding the types and causes of disruptive behavior, which fall into the categories of inattention,…

  13. Competency-Based Adult Education Report.

    ERIC Educational Resources Information Center

    Bureau of Occupational and Adult Education (DHEW/OE), Washington, DC. Div. of Adult Education.

    This resource guide for adult education personnel describes programs and publications on APL (Adult Performance Level) and Competency-Based Adult Education (CBAE). Includes: (1) Descriptions of APL examination programs developed by the American College Testing Program, (2) brief description of Missouri project on the identification of adult basic…

  14. The Faith Development of Selected Adult Couples.

    ERIC Educational Resources Information Center

    Gorman, Margaret

    Theories and studies of adult development are largely confined to adult male career development and ignore a moral or faith dimension of adult development. To determine the faith and moral dimension of adult couples, three hypotheses were examined, i.e.,: (1) religion is a significant dimension in their consciousness; (2) the family is integrally…

  15. Instructional Resources. Training and Adult Education Resources.

    ERIC Educational Resources Information Center

    Wurster, Susann L., Ed.

    1995-01-01

    Describes training and adult education resources available from ERIC: "Applications of an Adult Motivational Instructional Design Model"; "Visual and Digital Technologies for Adult Learning"; "Applications of Computer-Aided Instruction in Adult Education and Literacy"; and "The San Diego CWELL Project. Report of…

  16. Literacy Education in Adult Basic Education

    ERIC Educational Resources Information Center

    Kruidenier, John

    2002-01-01

    Adult basic education programs, sometimes called adult basic and secondary education programs, typically serve adults over the age of sixteen who do not have a high school diploma and are no longer eligible for traditional secondary education programs. Although adult basic education (ABE) is situated apart from the elementary, secondary, and…

  17. 38 CFR 18.438 - Adult education.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2014-07-01 2014-07-01 false Adult education. 18.438 Section 18.438 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS (CONTINUED... Adult Education § 18.438 Adult education. A recipient that provides adult education may not, on...

  18. 38 CFR 18.438 - Adult education.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2011-07-01 2011-07-01 false Adult education. 18.438 Section 18.438 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS (CONTINUED... Adult Education § 18.438 Adult education. A recipient that provides adult education may not, on...

  19. 38 CFR 18.438 - Adult education.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2013-07-01 2013-07-01 false Adult education. 18.438 Section 18.438 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS (CONTINUED... Adult Education § 18.438 Adult education. A recipient that provides adult education may not, on...

  20. 38 CFR 18.438 - Adult education.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Adult education. 18.438 Section 18.438 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS (CONTINUED... Adult Education § 18.438 Adult education. A recipient that provides adult education may not, on...