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

Lack of prognostic significance of C-erbB-2 expression in low- and high- grade astrocytomas.

PubMed

Muallaoglu, Saik; Besen, Ali Ayberk; Ata, Alper; Mertsoylu, Huseyin; Arican, Ali; Kayaselcuk, Fazilet; Ozyilkan, Ozgur

2014-01-01

Astrocytic tumors, the most common primary glial tumors of the central nervous system, are classified from low to high grade according to the degree of anaplasia and presence of necrosis. Despite advances in therapeutic management of high grade astrocytic tumors, prognosis remains poor. In the present study, the frequency and prognostic significance of c-erb-B2 in astrocytic tumors was investigated. Records of 72 patients with low- and high-grade astrocytic tumors were evaluated. The expression of C-erbB-2 was determined immunohistochemically and intensity was recorded as 0 to 3+. Tumors with weak staining (1+) or no staining (0) were considered Her-2 negative, while tumors with moderate (2+) and strong (3+) staining were considered Her-2 positive. Of the 72 patients, 41 (56.9%) had glioblastoma (GBM), 10 (13.9%) had diffuse astrocytoma, 15 (20.8%) had anaplastic astrocytoma, 6 (8.3%) had pilocytic astrocytoma. C-erbB-2 overexpression was detected in the tumor specimens of 17 patients (23.6%). Six (8.3%) tumors, all GBMs, exhibited strong staining, 2 (2.7%) specimens, both GBMs, exhibited moderate staining, and 9 specimens, 5 of them GBMs (12.5%), exhibited weak staining. No staining was observed in diffuse astrocytoma and pilocytic astrocytoma specimens. Median overall survival of patients with C-erbB-2 negative and C-erbB-2 positive tumors were 30 months (95%CI: 22.5-37.4 months) and 16.9 months (95%CI: 4.3-29.5 months), respectively (p=0.244). Although there was no difference in survival, C-erbB-2 overexpression was observed only in the GBM subtype.

[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.

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

Yoga Therapy in Treating Patients With Malignant Brain Tumors

ClinicalTrials.gov

2017-07-27

Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Meningioma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Choroid Plexus Tumor; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Recurrent Adult Brain Tumor

Survival Associations Using Perfusion and Diffusion Magnetic Resonance Imaging in Patients With Histologic and Genetic Defined Diffuse Glioma World Health Organization Grades II and III.

PubMed

Latysheva, Anna; Eeg Emblem, Kyrre; Server, Andrés; Brandal, Petter; Meling, Torstein R; Pahnke, Jens; Hald, John K

2018-06-12

According to the new World Health Organization 2016 classification for tumors of the central nervous system, 1p/19q codeletion defines the genetic hallmark that differentiates oligodendrogliomas from diffuse astrocytomas. The aim of our study was to evaluate whether relative cerebral blood volume (rCBV) and apparent diffusion coefficient (ADC) histogram analysis can stratify survival in adult patients with genetic defined diffuse glioma grades II and III. Sixty-seven patients with untreated diffuse gliomas World Health Organization grades II and III and known 1p/19q codeletion status were included retrospectively and analyzed using ADC and rCBV maps based on whole-tumor volume histograms. Overall survival and progression-free survival (PFS) were analyzed by using Kaplan-Meier and Cox survival analyses adjusted for known survival predictors. Significant longer PFS was associated with homogeneous rCBV distribution-higher rCBVpeak (median, 37 vs 26 months; hazard ratio [HR], 3.2; P = 0.02) in patients with astrocytomas, and heterogeneous rCBV distribution-lower rCBVpeak (median, 46 vs 37 months; HR, 5.3; P < 0.001) and higher rCBVmean (median, 44 vs 39 months; HR, 7.9; P = 0.003) in patients with oligodendrogliomas. Apparent diffusion coefficient parameters (ADCpeak, ADCmean) did not stratify PFS and overall survival. Tumors with heterogeneous perfusion signatures and high average values were associated with longer PFS in patients with oligodendrogliomas. On the contrary, heterogeneous perfusion distribution was associated with poor outcome in patients with diffuse astrocytomas.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Spontaneous anaplasia in pilocytic astrocytoma of cerebellum.

PubMed

Lach, B; Al Shail, E; Patay, Z

2003-06-01

We report a cystic cerebellar astrocytoma with a mural nodule that contained an additional focus of astrocytoma with the histological features of anaplasia, and showed up to 48% of aneuploid and 3% S-phase cells on flow cytometry. This focus was detectable on the enhanced, as well as non-enhanced T1 and T2 images. This appears to be the first case of pilocytic astrocytoma of cerebellum with focal anaplasia detected on histological and radiological studies.

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

Differentially Expressed Long Non-Coding RNAs Were Predicted to Be Involved in the Control of Signaling Pathways in Pediatric Astrocytoma.

PubMed

Ruiz Esparza-Garrido, Ruth; Rodríguez-Corona, Juan Manuel; López-Aguilar, Javier Enrique; Rodríguez-Florido, Marco Antonio; Velázquez-Wong, Ana Claudia; Viedma-Rodríguez, Rubí; Salamanca-Gómez, Fabio; Velázquez-Flores, Miguel Ángel

2017-10-01

Expression changes for long non-coding RNAs (lncRNAs) have been identified in adult glioblastoma multiforme (GBM) and in a mixture of adult and pediatric astrocytoma. Since adult and pediatric astrocytomas are molecularly different, the mixture of both could mask specific features in each. We determined the global expression patterns of lncRNAs and messenger RNA (mRNAs) in pediatric astrocytoma of different histological grades. Transcript expression changes were determined with an HTA 2.0 array. lncRNA interactions with microRNAs and mRNAs were predicted by using an algorithm and the LncTar tool, respectively. Interactomes were constructed with the HIPPIE database and visualized with the Cytoscape platform. The array showed expression changes in 156 and 207 lncRNAs in tumors (versus the control) and in pediatric GBM (versus low-grade astrocytoma), respectively. Predictions identified lncRNAs that have putative microRNA binding sites, which might suggest that they function as sponges in these tumors. Also, lncRNAs were shown to interact with many mRNAs, such as Pleckstrin homology-like domain, family A, member 1 (PHLDA1) and sulfatase 2 (SULF2). For example, qPCR found long intergenic non-coding RNA regulator of reprogramming (linc-RoR) expression levels upregulated in pediatric GBM when they were compared with control tissues or with low-grade tumors. Meanwhile, PHLDA1 and ELAV-like RNA binding protein 1 (ELAV1) showed expression changes in tumors relative to the control. Our data showed many lncRNAs with expression changes in pediatric astrocytoma, which might be involved in the regulation of different signaling pathways.

Anaplasia in pilocytic astrocytoma predicts aggressive behavior.

PubMed

Rodriguez, Fausto J; Scheithauer, Bernd W; Burger, Peter C; Jenkins, Sarah; Giannini, Caterina

2010-02-01

The clinical significance of anaplastic features, a rare event in pilocytic astrocytoma (PA), is not fully established. We reviewed 34 PA with anaplastic features (Male = 21, Female = 13; median age 35 y, 5 to 75) among approximately 2200 PA cases (1.7%). Tumors were included which demonstrated brisk mitotic activity [at least 4 mitoses/10 high power fields (400 x )], in addition to hypercellularity and moderate-to-severe cytologic atypia, with or without necrosis. The tumors either had a PA precursor, coexistent (n = 14) (41%) or documented by previous biopsy (n = 10) (29%), or exhibited typical pilocytic features in an otherwise anaplastic astrocytoma (n = 10) (29%). Clinical features of neurofibromatosis type-1 were present in 24% and a history of radiation for PA precursor in 12%. Histologically, the anaplastic component was classified as pilocytic like (41%), small cell (32%), epithelioid (15%), or fibrillary (12%). Median MIB1 labeling index was 24.7% in the anaplastic component and 2.6% in the precursor, although overlapping values were present. Strong p53 staining (3+) was limited to areas with anaplasia (19%), with overlapping values for 1 and 2+ in areas without anaplasia. Median overall and progression-free survivals after diagnosis for the entire study group were 24 and 14 months, respectively. Overall and progression-free survivals were shorter in the setting of prior radiation for a PA precursor (P = 0.007, 0.028), increasing mitotic activity (P = 0.03, 0.02), and presence of necrosis (P = 0.02, 0.02), after adjusting for age and site. The biologic behavior of PAs with high-mitotic rates and those with necrosis paralleled that of St Anne-Mayo grades 2 and 3 diffuse astrocytomas, respectively. In summary, PA with anaplastic features exhibits a spectrum of morphologies and is associated with decreased survival when compared with typical PA.

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

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

PubMed

Trogrlić, Ivo; Trogrlić, Dragan; Trogrlić, Zoran

2016-01-01

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

Childhood Astrocytoma Treatment (PDQ®)—Patient Version

Cancer.gov

Childhood astrocytoma treatment options include surgery, observation, radiation therapy, chemotherapy, high-dose chemotherapy with stem cell transplant, and targeted therapy. Learn more about the treatment of newly diagnosed and recurrent astrocytoma in this expert-reviewed summary.

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

PubMed

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

2012-06-15

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

Prognosis and Treatment of Spinal Cord Astrocytoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Minehan, Kiernan J.; Section of Radiation Oncology, Franciscan Skemp Healthcare, Mayo Health System, La Crosse, WI; Brown, Paul D.

2009-03-01

Purpose: To identify the prognostic factors for spinal cord astrocytoma and determine the effects of surgery and radiotherapy on outcome. Methods and Materials: This retrospective study reviewed the cases of consecutive patients with spinal cord astrocytoma treated at Mayo Clinic Rochester between 1962 and 2005. Results: A total of 136 consecutive patients were identified. Of these 136 patients, 69 had pilocytic and 67 had infiltrative astrocytoma. The median follow-up for living patients was 8.2 years (range, 0.08-37.6), and the median survival for deceased patients was 1.15 years (range, 0.01-39.9). The extent of surgery included incisional biopsy only (59%), subtotal resectionmore » (25%), and gross total resection (16%). Patients with pilocytic tumors survived significantly longer than those with infiltrative astrocytomas (median overall survival, 39.9 vs. 1.85 years; p < 0.001). Patients who underwent resection had a worse, although nonsignificant, median survival than those who underwent biopsy only (pilocytic, 18.1 vs. 39.9 years, p = 0.07; infiltrative, 19 vs. 30 months, p = 0.14). Postoperative radiotherapy, delivered in 75% of cases, gave no significant survival benefit for those with pilocytic tumors (39.9 vs. 18.1 years, p = 0.33) but did for those with infiltrative astrocytomas (24 vs. 3 months; Wilcoxon p = 0.006). On multivariate analysis, pilocytic histologic type, diagnosis after 1984, longer symptom duration, younger age, minimal surgical extent, and postoperative radiotherapy predicted better outcome. Conclusion: The results of our study have shown that histologic type is the most important prognostic variable affecting the outcome of spinal cord astrocytomas. Surgical resection was associated with shorter survival and thus remains an unproven treatment. Postoperative radiotherapy significantly improved survival for patients with infiltrative astrocytomas but not for those with pilocytic tumors.« less

WEE1 Inhibitor AZD1775 and Local Radiation Therapy in Treating Children With Newly Diagnosed Diffuse Intrinsic Pontine Gliomas

ClinicalTrials.gov

2018-06-11

Anaplastic Astrocytoma; Anaplastic Oligoastrocytoma; Diffuse Intrinsic Pontine Glioma; Diffuse Midline Glioma, H3 K27M-Mutant; Glioblastoma; Gliosarcoma; Untreated Childhood Anaplastic Astrocytoma; Untreated Childhood Anaplastic Oligoastrocytoma; Untreated Childhood Glioblastoma; Untreated Childhood Gliosarcoma

Expression of aquaporin8 in human astrocytomas: Correlation with pathologic grade

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhu, Shu-juan; Wang, Ke-jian; Gan, Sheng-wei

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 ofmore » 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.« less

The value of multi ultra high-b-value DWI in grading cerebral astrocytomas and its association with aquaporin-4.

PubMed

Tan, Yan; Zhang, Hui; Wang, Xiao-Chun; Qin, Jiang-Bo; Wang, Le

2018-06-01

To investigate the value of multi-ultrahigh-b-value diffusion-weighted imaging (UHBV-DWI) in differentiating high-grade astrocytomas (HGAs) from low-grade astrocytomas (LGAs), analyze its association with aquaporin (AQP) expression. 40 astrocytomas divided into LGAs (N = 15) and HGAs (N = 25) were studied. Apparent diffusion coefficient (ADC) and UHBV-ADC values in solid parts and peritumoral edema were compared between LGAs and HGAs groups by the t-test. Using receiver operating characteristic curves to identify the better parameter. Using real time polymerase chain reaction to assess AQP messenger ribonucleic acid (mRNA). Using spearman correlation analysis to assess the correlation of AQP mRNA with each parameter. ADC values in solid parts of HGAs were significantly lower than LGAs (p = 0.02), while UHBV-ADC values of HGAs were significantly higher than LGAs (p < 0.01). Area under the curve (AUC) of UHBV-ADC (0.810) was larger than ADC (0.713), and the area under the curve of UHBV-ADC was significantly higher than that of ADC (p = 0.041). AQP4 mRNA was significantly higher in HGAs than that in LGAs (p < 0.01); there was less AQP9 mRNA and no AQP1 mRNA in LGAs and HGAs groups (p > 0.05); ADC value showed a negative correlation with AQP4 mRNA (r = -0.357; p = 0.024). UHBV-ADC value positively correlated with the AQP4 mRNA (r = 0.646; p < 0.01). UHBV-DWI allowed for a more accurate grading of cerebral astrocytoma than DWI, and UHBV-ADC value may be related with the AQP4 mRNA levels. UHBV-DWI could be of value in the assessment of astrocytoma. Advances in knowledge: UHBV-DWI generated by multi UHBV could have particular value for astrocytoma grading, and the level of AQP4 mRNA might be potentially linked to the change of UHBV-DWI parameter, and we might find the exact reason for the difference of UHBV-ADC between the LGAs and HGAs.

Childhood Astrocytomas Treatment

MedlinePlus

... symptoms and almost all need treatment. The central nervous system controls many important body functions. Astrocytomas are most common in these parts of the central nervous system (CNS): Cerebrum : The largest part of the brain, ...

Effects of dexamethasone on C6 astrocytoma radiosensitivity

DOE Office of Scientific and Technical Information (OSTI.GOV)

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 timemore » 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.« less

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.

New study tests the safety and efficacy of combination therapy in adults with astrocytoma and glioblastoma | Center for Cancer Research

Cancer.gov

A two-part clinical trial of a multikinase inhibitor plus chemotherapy in patients with two types of brain tumors is enrolling in Bethesda, MD. The study will be open to patients with anaplastic astrocytoma, an uncommon malignant brain tumor that develops from star-shaped brain cells called astrocytes and glioblastoma, the most common and aggressive form of astrocytoma. Learn

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

ECT2 and RASAL2 mediate mesenchymal-amoeboid transition in human astrocytoma cells.

PubMed

Weeks, Adrienne; Okolowsky, Nadia; Golbourn, Brian; Ivanchuk, Stacey; Smith, Christian; Rutka, James T

2012-08-01

Malignant astrocytomas are highly invasive brain tumors. The Rho family of cytoskeletal GTPases are key regulators of astrocytoma migration and invasion; expression of the guanine nucleotide exchange factor ECT2 is elevated in primary astrocytomas and predicts both survival and malignancy. Mice bearing orthotopically implanted astrocytoma cells with diminished ECT2 levels following ECT2 knockdown exhibit longer survival. Although ECT2 is normally expressed in the nucleus, we show that ECT2 is aberrantly localized to the cytoplasm in both astrocytoma cell lines and primary human astrocytomas, and colocalizes with RAC1 and CDC42 at the leading edge of migrating astrocytoma cells. Inhibition of ECT2 expression by RNA interference resulted in decreased RAC1 and CDC42 activity, but no change in RHO activity, suggesting that ECT2 is capable of activating these pro-migratory Rho family members. ECT2 overexpression in astrocytoma cells resulted in a transition to an amoeboid phenotype that was abolished with the ROCK inhibitor, Y-27632. Cytoplasmic fractionation of astrocytoma cells followed by ECT2 immunoprecipitation and mass spectrometry were used to identify protein-binding partners that modulate the activity of ECT2 toward RAC1 and RHO/ROCK. We identified RASAL2 as an ECT2-interacting protein that regulates RHO activity in astrocytoma cells. RASAL2 knockdown leads to a conversion to an amoeboid phenotype. Our studies reveal that ECT2 has a novel role in mesenchymal-amoeboid transition in human astrocytoma cells. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

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

Fas ligand expression by astrocytoma in vivo: maintaining immune privilege in the brain?

PubMed Central

Saas, P; Walker, P R; Hahne, M; Quiquerez, A L; Schnuriger, V; Perrin, G; French, L; Van Meir, E G; de Tribolet, N; Tschopp, J; Dietrich, P Y

1997-01-01

Astrocytomas are among the most common brain tumors that are usually fatal in their malignant form. They appear to progress without significant impedance from the immune system, despite the presence of intratumoral T cell infiltration. To date, this has been thought to be the result of T cell immunosuppression induced by astrocytoma-derived cytokines. Here, we propose that cell contact-mediated events also play a role, since we demonstrate the in vivo expression of Fas ligand (FasL/CD95L) by human astrocytoma and the efficient killing of Fas-bearing cells by astrocytoma lines in vitro and by tumor cells ex vivo. Functional FasL is expressed by human, mouse, and rat astrocytoma and hence may be a general feature of this nonlymphoid tumor. In the brain, astrocytoma cells can potentially deliver a death signal to Fas+ cells which include infiltrating leukocytes and, paradoxically, astrocytoma cells themselves. The expression of FasL by astrocytoma cells may extend the processes that are postulated to occur in normal brain to maintain immune privilege, since we also show FasL expression by neurons. Overall, our findings suggest that FasL-induced apoptosis by astrocytoma cells may play a significant role in both immunosuppression and the regulation of tumor growth within the central nervous system. PMID:9077524

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.

Frontal lobe astrocytoma following radiotherapy for medulloblastoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

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.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hou, P; Park, P; Li, H

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 withmore » 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.« less

Alterations of the levels of primary antioxidant enzymes in different grades of human astrocytoma tissues.

PubMed

Yen, Hsiu-Chuan; Lin, Chih-Lung; Chen, Bing-Shian; Chen, Chih-Wei; Wei, Kuo-Chen; Yang, Mei-Lin; Hsu, Jee-Ching; Hsu, Yung-Hsing

2018-06-03

Malignant astrocytoma is the most commonly occurring brain tumor in humans. Oxidative stress is implicated in the development of cancers. Superoxide dismutase 2 (SOD2) was found to exert tumor suppressive effect in basic research, but increased SOD2 protein level was associated with higher aggressiveness of human astrocytomas. However, studies reporting alterations of antioxidant enzymes in human astrocytomas often employed less accurate methods or included different types of tumors. Here we analyzed the mRNA levels, activities, and protein levels of primary antioxidant enzymes in control brain tissues and various grades of astrocytomas obtained from 40 patients. SOD1 expression, SOD1 activity, and SOD1 protein level were lower in Grade IV astrocytomas. SOD2 expression was lower in low-grade (Grades I and II) and Grade III astrocytomas than in controls, but SOD2 expression and SOD2 protein level were higher in Grade IV astrocytomas than in Grade III astrocytomas. Although there was no change in SOD2 activity and a lower activity of citrate synthase (CS), the MnSOD:CS ratio increased in Grade IV astrocytomas compared with controls and low-grade astrocytomas. Furthermore, SOD1 activity, CS activity, SOD1 expression, GPX4 expression, and GPX4 protein level were inversely correlated with the malignancy, whereas catalase activity, catalase protein, SOD2 protein level, and the SOD2:CS ratio were positively correlated with the degree of malignancy. Lower SOD2:CS ratio was associated with poor outcomes for Grade IV astrocytomas. This is the first study to quantify changes of various primary antioxidant enzymes in different grades of astrocytomas at different levels concurrently in human astrocytomas.

Determining the relationship between "microvessel density" and different grades of astrocytoma based on immunohistochemistry for "factor VIII-related antigen" (von Willebrand factor) expression in tumor microvessels.

PubMed

Mahzouni, Parvin; Mohammadizadeh, Fereshteh; Mougouei, Kourosh; Moghaddam, Noushin Afshar; Chehrei, Ali; Mesbah, Alireza

2010-01-01

Astrocytic brain tumors are the most common primary central nervous system tumors, which are classified into four grades. One of the most important pathologic criteria for the diagnosis of higher-grade astrocytomas (especially glioblastoma multiforme) is microvessel proliferation, particularly in the form of glomeruloid complex. Because tumor angiogenesis is a necessary factor for growth and invasiveness of malignancies, microvessel density (MVD) and intensity of angiogenesis may be used to determine the grade of astrocytomas and plan therapy accordingly. We have planned this study to evaluate the relationship between vwf expression in microvessels and different grades of astrocytoma. Sixty-four formalin-fixed and paraffin-embedded blocks of surgical specimens with diagnosis of astrocytoma (grades I to IV, each of them 16 blocks) were selected in a simple-nonrandom sampling. Thin sections of tissue blocks underwent immunohistochemical staining for vwf. The stained slides were examined using a light microscope at low (100) and high (400) magnifications. MVD was estimated by calculating the mean number of stained microvessels in three areas of highest vascularization in the high-power field (400). The intensity of staining was determined based on a 3 scale model, in which scores 0, 1, 2, and 3 mean no detectable stain, trace staining, moderate amount of diffuse stain, and strong diffuse staining, respectively. Thirty-six (56%) patients were male and 28 (44%) were female. Scores 0 and 1 of microvessel staining intensity were not observed in any grades studied, but severe staining intensity (score 3) was observed in 18.8%, 37.5%, 56.3%, and 87.5% of grades I, II, III, and IV astrocytomas, respectively. "Vwf vessel index" (MVD staining intensity of microvessels) was 23.84, 25.62, 31.62, and 62.43 in grades I, II, III, and IV astrocytomas, respectively. We found a significant relationship between staining intensity of vwf in microvessels and different grades of

Transcriptional Analysis of Aggressiveness and Heterogeneity across Grades of Astrocytomas

PubMed Central

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

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

Histogram Analysis of Diffusion Tensor Imaging Parameters in Pediatric Cerebellar Tumors.

PubMed

Wagner, Matthias W; Narayan, Anand K; Bosemani, Thangamadhan; Huisman, Thierry A G M; Poretti, Andrea

2016-05-01

Apparent diffusion coefficient (ADC) values have been shown to assist in differentiating cerebellar pilocytic astrocytomas and medulloblastomas. Previous studies have applied only ADC measurements and calculated the mean/median values. Here we investigated the value of diffusion tensor imaging (DTI) histogram characteristics of the entire tumor for differentiation of cerebellar pilocytic astrocytomas and medulloblastomas. Presurgical DTI data were analyzed with a region of interest (ROI) approach to include the entire tumor. For each tumor, histogram-derived metrics including the 25th percentile, 75th percentile, and skewness were calculated for fractional anisotropy (FA) and mean (MD), axial (AD), and radial (RD) diffusivity. The histogram metrics were used as primary predictors of interest in a logistic regression model. Statistical significance levels were set at p < .01. The study population included 17 children with pilocytic astrocytoma and 16 with medulloblastoma (mean age, 9.21 ± 5.18 years and 7.66 ± 4.97 years, respectively). Compared to children with medulloblastoma, children with pilocytic astrocytoma showed higher MD (P = .003 and P = .008), AD (P = .004 and P = .007), and RD (P = .003 and P = .009) values for the 25th and 75th percentile. In addition, histogram skewness showed statistically significant differences for MD between low- and high-grade tumors (P = .008). The 25th percentile for MD yields the best results for the presurgical differentiation between pediatric cerebellar pilocytic astrocytomas and medulloblastomas. The analysis of other DTI metrics does not provide additional diagnostic value. Our study confirms the diagnostic value of the quantitative histogram analysis of DTI data in pediatric neuro-oncology. Copyright © 2015 by the American Society of Neuroimaging.

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. © 2012 The Authors; Brain Pathology © 2012 International Society of Neuropathology.

Testin (TES) as a candidate tumour suppressor and prognostic marker in human astrocytoma.

PubMed

Steponaitis, Giedrius; Kazlauskas, Arunas; Skiriute, Daina; Valiulyte, Indre; Skauminas, Kestutis; Tamasauskas, Arimantas; Vaitkiene, Paulina

2016-11-01

Astrocytomas are one of the most common brain tumours; however, the current methods used to characterize these tumours are inadequate. The establishment of molecular markers may identify variables required to improve tumour characterization and subtyping, and may aid to specify targets for improved treatment with essential prognostic value for patient survival. One such candidate is testin (TES), which was reported to have prognostic value for glioblastoma patients. However, the role of TES protein in gliomagenesis is currently unknown. In the present study, the methylation status of the TES promoter was investigated in post-operative astrocytoma tumours of different malignancy grade, and its association with the survival of astrocytoma patients was evaluated. In addition, the expression of TES protein was investigated in the same set of astrocytoma tumours tissue, and the association of protein expression with glioma patients survival was evaluated. The methylation status of TES was assessed by methylation-specific polymerase chain reaction in 138 different grade astrocytoma samples. Western blot analysis was used to characterize the expression pattern of TES in 86 different grade astrocytoma specimens: 13 of pathological grade I, 31 of pathological grade II, 17 of pathological grade III and 25 of pathological grade IV (glioblastoma). Statistical analyses were conducted to investigate the association between tumour molecular pattern, patient clinical variables and overall survival. The methylation analysis of the TES promoter exhibited a distinct profile between astrocytomas of different malignancy grade (P<0.001). Furthermore, gene promoter methylation was significantly associated with patients' age, survival and pathological grade (P<0.001). The protein expression level of TES was significantly lower in glioblastoma (grade IV astrocytoma) than in lower grade (II-III) astrocytoma tissue (P=0.028 and P=0.04, respectively). Additionally, short overall survival of

Testin (TES) as a candidate tumour suppressor and prognostic marker in human astrocytoma

PubMed Central

Steponaitis, Giedrius; Kazlauskas, Arunas; Skiriute, Daina; Valiulyte, Indre; Skauminas, Kestutis; Tamasauskas, Arimantas; Vaitkiene, Paulina

2016-01-01

Astrocytomas are one of the most common brain tumours; however, the current methods used to characterize these tumours are inadequate. The establishment of molecular markers may identify variables required to improve tumour characterization and subtyping, and may aid to specify targets for improved treatment with essential prognostic value for patient survival. One such candidate is testin (TES), which was reported to have prognostic value for glioblastoma patients. However, the role of TES protein in gliomagenesis is currently unknown. In the present study, the methylation status of the TES promoter was investigated in post-operative astrocytoma tumours of different malignancy grade, and its association with the survival of astrocytoma patients was evaluated. In addition, the expression of TES protein was investigated in the same set of astrocytoma tumours tissue, and the association of protein expression with glioma patients survival was evaluated. The methylation status of TES was assessed by methylation-specific polymerase chain reaction in 138 different grade astrocytoma samples. Western blot analysis was used to characterize the expression pattern of TES in 86 different grade astrocytoma specimens: 13 of pathological grade I, 31 of pathological grade II, 17 of pathological grade III and 25 of pathological grade IV (glioblastoma). Statistical analyses were conducted to investigate the association between tumour molecular pattern, patient clinical variables and overall survival. The methylation analysis of the TES promoter exhibited a distinct profile between astrocytomas of different malignancy grade (P<0.001). Furthermore, gene promoter methylation was significantly associated with patients' age, survival and pathological grade (P<0.001). The protein expression level of TES was significantly lower in glioblastoma (grade IV astrocytoma) than in lower grade (II–III) astrocytoma tissue (P=0.028 and P=0.04, respectively). Additionally, short overall survival of

A comprehensive review of paediatric low-grade diffuse glioma: pathology, molecular genetics and treatment.

PubMed

Ryall, Scott; Tabori, Uri; Hawkins, Cynthia

2017-04-01

Gliomas are the most common central nervous system neoplasms affecting children and can be both high- and low-grade. Paediatric low-grade glioma may be either World Health Organization grade I or grade II. Despite being classified as grade II diffuse astrocytoma, these neoplasms arising in children are distinct clinically and molecularly from their adult counterparts. They do not tend to progress to higher grade lesions and only rarely harbour an IDH mutation. Here, we review the clinical, histologic and molecular features of paediatric grade II diffuse glioma, highlighting their diagnostic criteria, prevalence across brain locations, their most common molecular features and how to test for them, and lastly the current status of therapeutic options available for their treatment.

Genomic analysis of diffuse pediatric low-grade gliomas identifies recurrent oncogenic truncating rearrangements in the transcription factor MYBL1

PubMed Central

Ramkissoon, Lori A.; Horowitz, Peleg M.; Craig, Justin M.; Ramkissoon, Shakti H.; Rich, Benjamin E.; Schumacher, Steven E.; McKenna, Aaron; Lawrence, Michael S.; Bergthold, Guillaume; Brastianos, Priscilla K.; Tabak, Barbara; Ducar, Matthew D.; Van Hummelen, Paul; MacConaill, Laura E.; Pouissant-Young, Tina; Cho, Yoon-Jae; Taha, Hala; Mahmoud, Madeha; Bowers, Daniel C.; Margraf, Linda; Tabori, Uri; Hawkins, Cynthia; Packer, Roger J.; Hill, D. Ashley; Pomeroy, Scott L.; Eberhart, Charles G.; Dunn, Ian F.; Goumnerova, Liliana; Getz, Gad; Chan, Jennifer A.; Santagata, Sandro; Hahn, William C.; Stiles, Charles D.; Ligon, Azra H.; Kieran, Mark W.; Beroukhim, Rameen; Ligon, Keith L.

2013-01-01

Pediatric low-grade gliomas (PLGGs) are among the most common solid tumors in children but, apart from BRAF kinase mutations or duplications in specific subclasses, few genetic driver events are known. Diffuse PLGGs comprise a set of uncommon subtypes that exhibit invasive growth and are therefore especially challenging clinically. We performed high-resolution copy-number analysis on 44 formalin-fixed, paraffin-embedded diffuse PLGGs to identify recurrent alterations. Diffuse PLGGs exhibited fewer such alterations than adult low-grade gliomas, but we identified several significantly recurrent events. The most significant event, 8q13.1 gain, was observed in 28% of diffuse astrocytoma grade IIs and resulted in partial duplication of the transcription factor MYBL1 with truncation of its C-terminal negative-regulatory domain. A similar recurrent deletion-truncation breakpoint was identified in two angiocentric gliomas in the related gene v-myb avian myeloblastosis viral oncogene homolog (MYB) on 6q23.3. Whole-genome sequencing of a MYBL1-rearranged diffuse astrocytoma grade II demonstrated MYBL1 tandem duplication and few other events. Truncated MYBL1 transcripts identified in this tumor induced anchorage-independent growth in 3T3 cells and tumor formation in nude mice. Truncated transcripts were also expressed in two additional tumors with MYBL1 partial duplication. Our results define clinically relevant molecular subclasses of diffuse PLGGs and highlight a potential role for the MYB family in the biology of low-grade gliomas. PMID:23633565

RTEL1 and TERT polymorphisms are associated with astrocytoma risk in the Chinese Han population.

PubMed

Jin, Tian-Bo; Zhang, Jia-Yi; Li, Gang; Du, Shu-Li; Geng, Ting-Ting; Gao, Jing; Liu, Qian-Ping; Gao, Guo-Dong; Kang, Long-Li; Chen, Chao; Li, Shan-Qu

2013-12-01

Common variants of multiple genes play a role in glioma onset. However, research related to astrocytoma, the most common primary brain neoplasm, is rare. In this study, we chose 21 tagging SNPs (tSNPs), previously reported to be associated with glioma risk in a Chinese case-control study from Xi'an, China, and identified their contributions to astrocytoma susceptibility. We found an association with astrocytoma susceptibility for two tSNPs (rs6010620 and rs2853676) in two different genes: regulator of telomere elongation helicase 1 (RTEL1) and telomerase reverse transcriptase (TERT), respectively. We confirmed our results using recessive, dominant, and additive models. In the recessive model, we found two tSNPs (rs2297440 and rs6010620) associated with increased astrocytoma risk. In the dominant model, we found that rs2853676 was associated with increased astrocytoma risk. In the additive model, all three tSNPs (rs2297440, rs2853676, and rs6010620) were associated with increased astrocytoma risk. Our results demonstrate, for the first time, the potential roles of RTEL1 and TERT in astrocytoma development.

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.

PDGFRA amplification is common in pediatric and adult high-grade astrocytomas and identifies a poor prognostic group in IDH1 mutant glioblastoma

PubMed Central

Phillips, Joanna J.; Aranda, Derick; Ellison, David W.; Judkins, Alexander R.; Croul, Sidney E.; Brat, Daniel J.; Ligon, Keith L.; Horbinski, Craig; Venneti, Sriram; Zadeh, Gelareh; Santi, Mariarita; Zhou, Shengmei; Appin, Christina L.; Sioletic, Stefano; Sullivan, Lisa M.; Martinez-Lage, Maria; Robinson, Aaron E.; Yong, William H.; Cloughesy, Timothy; Lai, Albert; Phillips, Heidi S.; Marshall, Roxanne; Mueller, Sabine; Haas-Kogan, Daphne A.; Molinaro, Annette M.; Perry, Arie

2013-01-01

High-grade astrocytomas (HGAs), corresponding to WHO grades III (AA) and IV (GBM), are biologically aggressive and their molecular classification is increasingly relevant to clinical management. PDGFRA amplification is common in HGAs, although its prognostic significance remains unclear. Using fluorescence in situ hybridization (FISH), the most sensitive technique for detecting PDGFRA copy number gains, we determined PDGFRA amplification status in 123 pediatric and 263 adult HGAs. A range of PDGFRA FISH patterns were identified and cases were scored as non-amplified (normal and polysomy) or amplified (low-level and high-level). PDGFRA amplification was frequent in pediatric (29.3%) and adult (20.9%) tumors. Amplification was not prognostic in pediatric HGAs. In adult tumors diagnosed initially as GBM, the presence of combined PDGFRA amplification and IDH1R132H mutation was a significant independent prognostic factor (p=0.01). In HGAs, PDGFRA amplification is common and can manifest as high-level and focal or low-level amplifications. Our data indicate that the latter is more prevalent than previously reported with copy number averaging techniques. To our knowledge, this is the largest survey of PDGFRA status in adult and pediatric HGAs and suggests PDGFRA amplification increases with grade and is associated with a less favorable prognosis in IDH1 mutant de novo GBMs. PMID:23438035

Retinal astrocytoma in a dog.

PubMed

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

2017-09-01

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

Recurrent somatic alterations of FGFR1 and NTRK2 in pilocytic astrocytoma

PubMed Central

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

2014-01-01

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

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

EMMPRIN expression positively correlates with WHO grades of astrocytomas and meningiomas.

PubMed

Tsai, Wen-Chiuan; Chen, Ying; Huang, Li-Chun; Lee, Herng-Sheng; Ma, Hsin-I; Huang, Shih-Ming; Sytwu, Huey-Kang; Hueng, Dueng-Yuan

2013-09-01

High-grade primary brain tumors possessed poor outcome due to invasiveness. Extracellular matrix metalloproteinase inducer (EMMPRIN) stimulates peri-tumoral fibroblasts to secrete matrix metalloproteinase and promote invasiveness. This study hypothesized that high-grade brain tumors overexpress EMMPRIN. Analyzing the public delinked database from the Gene Expression Omnibus profile, the results showed that the EMMPRIN mRNA level was higher in WHO grade IV (n = 81) than in grade III (n = 19, p < 0.0005) astrocytomas and non-tumor brain tissue controls (n = 23, p < 0.00001). The results of tissue microarray-based immunohistochemical (IHC) staining revealed that EMMPRIN levels positively correlated with WHO grades for astrocytomas (p = 0.008) and meningiomas (p = 0.048). EMMPRIN mRNA levels in conventional glioma cell lines (n = 36) was not less than those in glioma primary culture cells (n = 27) and glioblastoma stem-like cells (n = 12). The GBM8401, U87MG, and LN229 human glioma cell lines also overexpressed EMMPRIN. Hematoxylin and eosin, IHC, and immunofluorescence staining of xenografts confirmed that high-grade brain tumors overexpressed EMMPRIN. Lastly, Kaplan-Meier analysis revealed poorer survival in WHO grade IV (n = 56) than in grade III astrocytomas (n = 21, by log-rank test; p = 0.0001, 95 % CI: 1.842-3.053). However, in high-grade astrocytomas, there was no difference in survival between high and low EMMPRIN mRNA levels. Thus, this study identified that high-grade brain tumors overexpress EMMPRIN, which positively correlates with WHO grades in human astrocytomas and meningiomas, and suggests that EMMPRIN may be a therapeutic target of brain tumor.

Extracranial bone metastases from recurrent anaplastic astrocytoma on FDG PET/CT

PubMed Central

Li, Zu-Gui; Mu, Hai-Yu

2017-01-01

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

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. Copyright © 2016 Elsevier Inc. All rights reserved.

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

PubMed

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

2014-06-01

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

Retrobulbar anaplastic astrocytoma in a dog: clinicopathological and ultrasonographic features.

PubMed

Martín, E; Pérez, J; Mozos, E; López, R; Molleda, J M

2000-08-01

An 11-year-old entire female German shepherd dog was presented with a progressive non-painful exophthalmos of the right eye. Ultrasonographic examination revealed a solid and well-defined orbital mass compressing the globe. Thoracic radiography revealed multiple pulmonary metastases of different sizes. The histopathological and immunohistochemical features of both the retrobulbar tumour and pulmonary metastases were consistent with an anaplastic astrocytoma. This represents an unusual case of an extracranial astrocytoma with multiple pulmonary metastases. The clinical features and the ultrasonographic, histopathological and immunohistochemical findings are described.

Pre-Surgical Integration of fMRI and DTI of the Sensorimotor System in Transcortical Resection of a High-Grade Insular Astrocytoma

PubMed Central

Ekstrand, Chelsea L.; Mickleborough, Marla J. S.; Fourney, Daryl R.; Gould, Layla A.; Lorentz, Eric J.; Ellchuk, Tasha; Borowsky, Ron W.

2016-01-01

Herein we report on a patient with a WHO Grade III astrocytoma in the right insular region in close proximity to the internal capsule who underwent a right frontotemporal craniotomy. Total gross resection of insular gliomas remains surgically challenging based on the possibility of damage to the corticospinal tracts. However, maximizing the extent of resection has been shown to decrease future adverse outcomes. Thus, the goal of such surgeries should focus on maximizing extent of resection while minimizing possible adverse outcomes. In this case, pre-surgical planning included integration of functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI), to localize motor and sensory pathways. Novel fMRI tasks were individually developed for the patient to maximize both somatosensory and motor activation simultaneously in areas in close proximity to the tumor. Information obtained was used to optimize resection trajectory and extent, facilitating gross total resection of the astrocytoma. Across all three motor-sensory tasks administered, fMRI revealed an area of interest just superior and lateral to the astrocytoma. Further, DTI analyses showed displacement of the corona radiata around the superior dorsal surface of the astrocytoma, extending in the direction of the activation found using fMRI. Taking into account these results, a transcortical superior temporal gyrus surgical approach was chosen in order to avoid the area of interest identified by fMRI and DTI. Total gross resection was achieved and minor post-surgical motor and sensory deficits were temporary. This case highlights the utility of comprehensive pre-surgical planning, including fMRI and DTI, to maximize surgical outcomes on a case-by-case basis. PMID:27013996

Progesterone induces the growth and infiltration of human astrocytoma cells implanted in the cerebral cortex of the rat.

PubMed

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  μ L), 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.

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

Unusual MR spectroscopic imaging pattern of an astrocytoma: lack of elevated choline and high myo-inositol and glycine levels.

PubMed

Londoño, Ana; Castillo, Mauricio; Armao, Diane; Kwock, Lester; Suzuki, Kinuko

2003-05-01

We present the case of a patient with an MR imaging study showing an ill-defined intra-axial mass in the right insula and frontal lobe. The mass showed high signal intensity on T2-weighted and fluid-attenuated inversion recovery images and an unusual proton MR spectroscopic imaging pattern characterized by the presence of high levels of myo-inositol/glycine, no significant elevation of choline, and mildly reduced N-acetylaspartate. The histopathologic diagnosis was of diffuse astrocytoma with oligodendroglial components (World Health Organization grade II).

[Diagnostic imaging of high-grade astrocytoma: heterogeneity of clinical manifestation, image characteristics, and histopathological findings].

PubMed

Okajima, Kaoru; Ohta, Yoshio

2012-10-01

Recent developments in diagnostic radiology, which have enabled accurate differential diagnoses of brain tumors, have been well described in the last three decades. MR and PET imaging can also provide information to predict histological grades and prognoses that might influence treatment strategies. However, high-grade astrocytomas consist of many different subtypes that are associated with different imaging and histological characteristics. Hemorrhage and necrosis results in a variety of imaging features, and infiltrative tumor growth entrapping normal neurons may cause different clinical manifestations. We reviewed patients with high-grade astrocytomas that showed various imaging characteristics, with special emphasis on initial symptoms and histological features. Clinicopathological characteristics of astrocytomas were also compared with other malignant tumors. Neurological deficits were not notable in patients with grade 3-4 astrocytomas when they showed infiltrative tumor growth, while brain metastases with compact cellular proliferation caused more neurological symptoms. Infiltrative tumors did not show any enhancing masses on MR imaging, but these tumors may show intratumor heterogeneity. Seizures were reported to be more frequent in low-grade glioma and in secondary glioblastoma. Tumor heterogeneity was also reported in molecular genetic profile, and investigators identified some subsets of astrocytomas. They investigated IHD1/2 mutation, EGFR amplification, TP53 mutation, Ki-67 index, etc. In summary, high-grade astrocytomas are not homogenous groups of tumors, and this is associated with the heterogeneity of clinical manifestation, image characteristics, and histopathological findings. Molecular studies may explain the tumor heterogeneity in the near future.

Inhibition of formyl peptide receptor in high-grade astrocytoma by CHemotaxis Inhibitory Protein of S. aureus

PubMed Central

Boer, J C; Domanska, U M; Timmer-Bosscha, H; Boer, I G J; de Haas, C J C; Joseph, J V; Kruyt, F A E; de Vries, E G E; den Dunnen, W F A; van Strijp, J A G; Walenkamp, A M E

2013-01-01

Background: High-grade astrocytomas are malignant brain tumours that infiltrate the surrounding brain tissue and have a poor prognosis. Activation of formyl peptide receptor (FPR1) on the human astrocytoma cell line U87 promotes cell motility, growth and angiogenesis. We therefore investigated the FPR1 inhibitor, Chemotaxis Inhibitory Protein of S. aureus (CHIPS), as a potential anti-astrocytoma drug. Methods and results: FPR1 expression was studied immunohistochemically in astrocytomas WHO grades I–IV. With intracellular calcium mobilisation and migration assays, human ligands were tested for their ability to activate FPR1 on U87 cells and on a cell line derived from primary astrocytoma grade IV patient material. Thereafter, we selectively inhibited these ligand-induced responses of FPR1 with an anti-inflammatory compound called Chemotaxis Inhibitory Protein of S. aureus (CHIPS). U87 xenografts in NOD-SCID mice served to investigate the effects of CHIPS in vivo. FPR1 was expressed in 29 out of 32 (90%) of all grades of astrocytomas. Two human mitochondrial-derived formylated peptides, formyl-methionil-leucine-lysine-isoleucine-valine (fMLKLIV) and formyl-methionil-methionil-tyrosine-alanine-leucine-phenylalanine (fMMYALF), were potent activators of FPR1 on tumour cells. Ligand-induced responses of FPR1-expressing tumour cells could be inhibited with FPR1 inhibitor CHIPS. Treatment of tumour-bearing mice with CHIPS slightly reduced tumour growth and improved survival as compared to non-treated animals (P=0.0019). Conclusion: Targeting FPR1 with CHIPS reduces cell motility and tumour cell activation, and prolongs the survival of tumour-bearing mice. This strategy could be explored in future research to improve treatment results for astrocytoma patients. PMID:23322202

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

Low-Grade Astrocytoma within a Mature Cystic Teratoma in an Adolescent Patient.

PubMed

Yoder, Nicole; Marks, Asher; Hui, Pei; Litkouhi, Babak; Cron, Julia

2018-06-01

Mature cystic teratomas are the most common ovarian neoplasm in adolescents. They are typically benign, however, malignant transformation rarely occurs. We report a low-grade astrocytoma arising from a mature cystic teratoma in an adolescent patient. The patient was a 12-year-old girl with an asymptomatic ovarian cyst and subsequent cystectomy. Final pathology identified a solid tumor with glial tissue within the cyst, reported as low-grade astrocytoma arising in a mature cystic teratoma. There are few data on astrocytomas in the gynecologic tract. Risk factors for malignant transformation in a mature cystic teratoma include increased age, postmenopausal status, elevated carcinoma antigen 125, and large tumor size. Interestingly, this patient had a history of partial trisomy 20, which has been associated with teratoma formation in a mouse model. Copyright © 2017 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2017-02-01

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

Dominant-negative mutants of platelet-derived growth factor revert the transformed phenotype of human astrocytoma cells.

PubMed Central

Shamah, S M; Stiles, C D; Guha, A

1993-01-01

Malignant astrocytoma is the most common primary human brain tumor. Most astrocytomas express a combination of platelet-derived growth factor (PDGF) and PDGF receptor which could close an autocrine loop. It is not known whether these autocrine loops contribute to the transformed phenotype of astrocytoma cells or are incidental to that phenotype. Here we show that dominant-negative mutants of the PDGF ligand break the autocrine loop and revert the phenotype of BALB/c 3T3 cells transformed by the PDGF-A or PDGF-B (c-sis) gene. Then, we show that these mutants are selective in that they do not alter the phenotype of 3T3 cells transformed by an activated Ha-ras or v-src gene or by simian virus 40. Finally, we show that these mutants revert the transformed phenotype of two independent human astrocytoma cell lines. They have no effect on the growth of human medulloblastoma, bladder carcinoma, or colon carcinoma cell lines. These observations are consistent with the view that PDGF autocrine loops contribute to the transformed phenotype of at least some human astrocytomas. Images PMID:8246942

Childhood Astrocytomas Treatment (PDQ®)—Health Professional Version

Cancer.gov

Astrocytoma is the most common type of glioma in children. Get detailed information about the clinical features, molecular and diagnostic evaluation, classification, prognosis, and treatment of newly diagnosed and recurrent disease low-grade and high-grade gliomas in this comprehensive summary for clinicians.

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

PubMed

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.

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

Farewell to oligoastrocytoma: in situ molecular genetics favor classification as either oligodendroglioma or astrocytoma.

PubMed

Sahm, Felix; Reuss, David; Koelsche, Christian; Capper, David; Schittenhelm, Jens; Heim, Stephanie; Jones, David T W; Pfister, Stefan M; Herold-Mende, Christel; Wick, Wolfgang; Mueller, Wolf; Hartmann, Christian; Paulus, Werner; von Deimling, Andreas

2014-10-01

Astrocytoma and oligodendroglioma are histologically and genetically well-defined entities. The majority of astrocytomas harbor concurrent TP53 and ATRX mutations, while most oligodendrogliomas carry the 1p/19q co-deletion. Both entities share high frequencies of IDH mutations. In contrast, oligoastrocytomas (OA) appear less clearly defined and, therefore, there is an ongoing debate whether these tumors indeed constitute an entity or whether they represent a mixed bag containing both astrocytomas and oligodendrogliomas. We investigated 43 OA diagnosed in different institutions employing histology, immunohistochemistry and in situ hybridization addressing surrogates for the molecular genetic markers IDH1R132H, TP53, ATRX and 1p/19q loss. In all but one OA the combination of nuclear p53 accumulation and ATRX loss was mutually exclusive with 1p/19q co-deletion. In 31/43 OA, only alterations typical for oligodendroglioma were observed, while in 11/43 OA, only indicators for mutations typical for astrocytomas were detected. A single case exhibited a distinct pattern, nuclear expression of p53, ATRX loss, IDH1 mutation and partial 1p/19q loss. However, this was the only patient undergoing radiotherapy prior to surgery, possibly contributing to the acquisition of this uncommon combination. In OA with oligodendroglioma typical alterations, the portions corresponding to astrocytic part were determined as reactive, while in OA with astrocytoma typical alterations the portions corresponding to oligodendroglial differentiation were neoplastic. These data provide strong evidence against the existence of an independent OA entity.

Hsp27 and its expression pattern in diffusely infiltrating astrocytomas.

PubMed

Mäkelä, Katri S; Haapasalo, Joonas A; Ilvesaro, Joanna M; Parkkila, Seppo; Paavonen, Timo; Haapasalo, Hannu K

2014-09-01

Heat shock protein 27 (Hsp27) is induced by cell stress conditions. In the presence of oxidative stress it functions as an antioxidant. To study the putative expression patterns and clinical significance of Hsp27, we assessed the associations between Hsp27, R132H mutation of Isocitrate dehydrogenase1 (IDH1-R132H), Hypoxia-inducible factor subunit alpha (HIF-1 alpha), Carbonic anhydrase IX (CA IX), and patient prognosis in astrocytic gliomas. Tissue micro-array samples of 295 grade II-IV astrocytomas were stained immunohistochemically for Hsp27, IDH1-R132H, HIF-1 alpha, and CA IX. We tested their relationship with clinicopathological features and patient survival. There was a significant correlation between Hsp27 expression and increasing WHO grade (p<0.001). Hsp27 expression correlated significantly with IDH1 mutation when studied within the entire cohort (p<0.001) as well as separately in WHO grade II and III tumors (p=0.006 and 0.002, respectively). IDH1 mutation and HIF-1 alpha positive staining were detected simultaneously (p<0.001). In IDH1 mutated tumors, positive HIF-1 alpha staining correlated with CA IX expression (p=0.027), whereas no such correlation was found in IDH1 non-mutated tumors. IDH1 mutation was associated with a low cell proliferation index (p=0.001) and HIF-1 alpha with increasing proliferation (p = 0.003). Hsp27 expression was associated with a shorter rate of patient survival in univariate survival analysis (p=0.001). In multivariate survival analysis, patient age, IDH1 mutation and HIF-1 alpha appeared as independent prognostic factors (p<0.000, <0.000 and 0.011 respectively) Hsp27 expression is associated with increasing WHO grade and patient prognosis in astrocytic gliomas. The results suggest that IDH1 mutation may have an effect on the expression pathways of Hsp27 and CA IX.

TCGA_LowerGradeGliomas

Cancer.gov

TCGA researchers analyzed nearly 300 cases of diffuse low- and intermediate-grade gliomas, which together comprise lower-grade gliomas. LGGs occur mainly in adults and include astrocytomas, oligodendrogliomas and oligoastrocytomas.

Genomic underpinnings of brain tumors - TCGA

Cancer.gov

TCGA researchers analyzed nearly 300 cases of diffuse low- and intermediate-grade gliomas, which together comprise lower-grade gliomas. LGGs occur mainly in adults and include astrocytomas, oligodendrogliomas and oligoastrocytomas.

CCNG2 Overexpression Mediated by AKT Inhibits Tumor Cell Proliferation in Human Astrocytoma Cells.

PubMed

Zhang, Danfeng; Wang, Chunhui; Li, Zhenxing; Li, Yiming; Dai, Dawei; Han, Kaiwei; Lv, Liquan; Lu, Yicheng; Hou, Lijun; Wang, Junyu

2018-01-01

The cyclin family protein CCNG2 has an important inhibitory role in cancer initiation and progression, but the exact mechanism is still unknown. In this study, we examined the relationship between CCNG2 and the malignancy of astrocytomas and whether the AKT pathway, which is upregulated in astrocytomas, may inhibit CCNG2 expression. CCNG2 expression was found to be negatively associated with the pathological grade and proliferative activity of astrocytomas, as the highest expression was found in control brain tissue ( N  = 31), whereas the lowest expression was in high-grade glioma tissue ( N  = 31). Additionally, CCNG2 overexpression in glioma cell lines, T98G and U251 inhibited proliferation and arrested cells in the G0/G1 phase. Moreover, CCNG2 overexpression could increase glioma cells apoptosis. In contrast, AKT activity increased in glioma cells that had low CCNG2 expression. Expression of CCNG2 was higher in cells treated with the AKT kinase inhibitor MK-2206 indicating that the presence of phosphorylated AKT may inhibit the expression of CCNG2. Inhibition of AKT also led to decreased colony formation in T98G and U251 cells and knocked down of CCNG2 reversed the result. Finally, overexpression of CCNG2 in glioma cells reduced tumor volume in a murine model. To conclude, low expression of CCNG2 correlated with the severity astrocytoma and CCNG2 overexpression could induce apoptosis and inhibit proliferation. Inhibition of AKT activity increased the expression of CCNG2. The present study highlights the regulatory consequences of CCNG2 expression and AKT activity in astrocytoma tumorigenesis and the potential use of CCNG2 in anticancer treatment.

MRS of pilocytic astrocytoma: The peak at 2 ppm may not be NAA.

PubMed

Tamrazi, Benita; Nelson, Marvin D; Blüml, Stefan

2017-08-01

To determine whether the chemical shift of residual N-acetylaspartate (NAA) signal in pilocytic astrocytomas (PA) is consistent with the position of the NAA peak in controls. MR spectra from 27 pediatric World Health Organization (WHO) grade I pilocytic astrocytoma patients, fifteen patients with WHO grade II and high-grade (III-IV) astrocytomas, and 36 controls were analyzed. All spectra were acquired with a short echo time (35 ms), single voxel point-resolved spectroscopy sequence on clinical 3 tesla scanners. Fully automated LCModel software was used for processing, which included the fitting of peak positions for NAA and creatine (Cr). The chemical shift difference between the NAA and Cr peaks was significantly smaller (by 0.016 ± 0.005 parts per million, P < 1e-10) in PAs than in controls and was also smaller than what was observed in infiltrative astrocytomas. The chemical shift position of the residual NAA peak in PAs is not consistent with NAA. The signal likely originates from an N-acetyl group of one or more other chemicals such as N-acetylated sugars. Magn Reson Med 78:452-456, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Management of Pediatric Spinal Cord Astrocytomas: Outcomes With Adjuvant Radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guss, Zachary D.; Moningi, Shalini; Jallo, George I.

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 weremore » 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

Outcome of Patients With Pilocytic Astrocytoma and Leptomeningeal Dissemination

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mazloom, Ali; Hodges, Joseph C.; Teh, Bin S.

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%, andmore » 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.« less

Axial diffusivity of the corona radiata correlated with ventricular size in adult hydrocephalus.

PubMed

Cauley, Keith A; Cataltepe, Oguz

2014-07-01

Hydrocephalus causes changes in the diffusion-tensor properties of periventricular white matter. Understanding the nature of these changes may aid in the diagnosis and treatment planning of this relatively common neurologic condition. Because ventricular size is a common measure of the severity of hydrocephalus, we hypothesized that a quantitative correlation could be made between the ventricular size and diffusion-tensor changes in the periventricular corona radiata. In this article, we investigated this relationship in adult patients with hydrocephalus and in healthy adult subjects. Diffusion-tensor imaging metrics of the corona radiata were correlated with ventricular size in 14 adult patients with acute hydrocephalus, 16 patients with long-standing hydrocephalus, and 48 consecutive healthy adult subjects. Regression analysis was performed to investigate the relationship between ventricular size and the diffusion-tensor metrics of the corona radiata. Subject age was analyzed as a covariable. There is a linear correlation between fractional anisotropy of the corona radiata and ventricular size in acute hydrocephalus (r = 0.784, p < 0.001), with positive correlation with axial diffusivity (r = 0.636, p = 0.014) and negative correlation with radial diffusivity (r = 0.668, p = 0.009). In healthy subjects, axial diffusion in the periventricular corona radiata is more strongly correlated with ventricular size than with patient age (r = 0.466, p < 0.001, compared with r = 0.058, p = 0.269). Axial diffusivity of the corona radiata is linearly correlated with ventricular size in healthy adults and in patients with hydrocephalus. Radial diffusivity of the corona radiata decreases linearly with ventricular size in acute hydrocephalus but is not significantly correlated with ventricular size in healthy subjects or in patients with long-standing hydrocephalus.

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.

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

PubMed

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

2016-02-01

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

Genomic analysis of the origins and evolution of multicentric diffuse lower-grade gliomas.

PubMed

Hayes, Josie; Yu, Yao; Jalbert, Llewellyn E; Mazor, Tali; Jones, Lindsey E; Wood, Matthew D; Walsh, Kyle M; Bengtsson, Henrik; Hong, Chibo; Oberndorfer, Stefan; Roetzer, Thomas; Smirnov, Ivan V; Clarke, Jennifer L; Aghi, Manish K; Chang, Susan M; Nelson, Sarah J; Woehrer, Adelheid; Phillips, Joanna J; Solomon, David A; Costello, Joseph F

2018-04-09

Rare multicentric lower-grade gliomas (LGGs) represent a unique opportunity to study the heterogeneity among distinct tumor foci in a single patient and to infer their origins and parallel patterns of evolution. In this study, we integrate clinical features, histology, and immunohistochemistry for 4 patients with multicentric LGG, arising both synchronously and metachronously. For 3 patients we analyze the phylogeny of the lesions using exome sequencing, including one case with a total of 8 samples from the 2 lesions. One patient was diagnosed with multicentric isocitrate dehydrogenase 1 (IDH1) mutated diffuse astrocytomas harboring distinct IDH1 mutations, R132H and R132C; the latter mutation has been associated with Li-Fraumeni syndrome, which was subsequently confirmed in the patient's germline DNA and shown in additional cases with The Cancer Genome Atlas data. In another patient, phylogenetic analysis of synchronously arising grade II and grade III diffuse astrocytomas demonstrated a single shared mutation, IDH1 R132H, and revealed convergent evolution via non-overlapping mutations in ATRX and TP53. In 2 cases, there was divergent evolution of IDH1-mutated and 1p/19q-codeleted oligodendroglioma and IDH1-mutated and 1p/19q-intact diffuse astrocytoma, occurring synchronously in one case and metachronously in a second. Each tumor in multicentric LGG cases may arise independently or may diverge very early in their development, presenting as genetically and histologically distinct tumors. Comprehensive sampling of these lesions can therefore significantly alter diagnosis and management. Additionally, somatic IDH1 R132C mutation in either multicentric or solitary LGG identifies unsuspected germline TP53 mutation, validating the limited number of published cases.

[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.

Human herpesvirus multiplex ddPCR detection in brain tissue from low- and high-grade astrocytoma cases and controls.

PubMed

Lin, Cheng-Te Major; Leibovitch, Emily C; Almira-Suarez, M Isabel; Jacobson, Steven

2016-01-01

Glioblastoma (GBM) is a fatal CNS malignancy, representing 50 % of all gliomas with approximately 12-18 months survival time after initial diagnosis. Recently, the human herpesvirus cytomegalovirus (CMV) has been suggested to have an oncogenic role, yet this association remains controversial. In addition, human herpesvirus 6 (HHV-6) and Epstein-Barr virus (EBV) have also been associated with low-grade gliomas, but few studies have examined HHV-6 and EBV in glioblastomas. Droplet digital PCR (ddPCR) is a highly precise diagnostic tool that enables the absolute quantification of target DNA. This study examines the association between multiple human herpesviruses and astrocytomas. This study analyzed 112 brain tissue specimens, including 45 glioblastoma, 12 astrocytoma grade III, 2 astrocytoma grade II, 4 astrocytoma grade I, and 49 controls. All brain tissue samples were de-identified and pathologically confirmed. Each tissue block was sectioned for DNA extraction and CMV, EBV, HHV-6A and HHV-6B, and a cellular housekeeping gene were amplified by ddPCR. Neither CMV nor HHV-6A were detected in any of the astrocytoma samples. However, HHV-6B (p = 0.147) and EBV (p = 0.049) had a higher positivity frequency in the GBM compared to the controls. The undetectable CMV DNA in the astrocytoma cohort does not support the observation of an increased prevalence of CMV DNA in GBM, as reported in other studies. EBV has a significantly higher positivity in the GBM cohort compared to the controls, while HHV-6B has a higher but not statistically significant positivity in the case cohort. Whether these viruses play an oncogenic role in GBM remains to be further investigated.

The role of chemotherapy in the treatment of malignant astrocytomas.

PubMed

Mathieu, David; Fortin, David

2006-05-01

Malignant astrocytomas are aggressive neoplasms with a dismal prognosis despite optimal treatment. Maximal resective surgery is traditionally complemented by radiation therapy. Chemotherapy is now used on patients as initial therapy when their functional status is congruent with further treatment. The classic agents used are nitrosoureas, but temozolomide has taken the front seat recently, with recent data demonstrating increased survival when this agent is used concurrently with radiation therapy in newly diagnosed glioblastoma patients. A new class of agents, refered to as biological modifiers, are increasingly used in clinical trials in an effort to affect the intrinsic biologic aberrations harboured by tumor cells. These drugs comprise differentiation agents, anti-angiogenic agents, matrix-metalloproteinase inhibitors and signal transduction inhibitors, among others. This article reviews the standard cytotoxic agents that have been used to treat malignant astrocytomas, and the different combination regimens offering promise. In addition, recent advances with biological modifiers are also discussed.

β2-Adrenergic Receptor Agonists Inhibit the Proliferation of 1321N1 Astrocytoma CellsS⃞

PubMed Central

Toll, L.; Jimenez, L.; Waleh, N.; Jozwiak, K.; Woo, A.Y.-H.; Xiao, R.-P.; Bernier, M.

2011-01-01

Astrocytomas and glioblastomas have been particularly difficult to treat and refractory to chemotherapy. However, significant evidence has been presented that demonstrates a decrease in astrocytoma cell proliferation subsequent to an increase in cAMP levels. The 1321N1 astrocytoma cell line, as well as other astrocytomas and glioblastomas, expresses β2-adrenergic receptors (β2-ARs) that are coupled to Gs activation and consequent cAMP production. Experiments were conducted to determine whether the β2-AR agonist (R,R′)-fenoterol and other β2-AR agonists could attenuate mitogenesis and, if so, by what mechanism. Receptor binding studies were conducted to characterize β2-AR found in 1321N1 and U118 cell membranes. In addition, cells were incubated with (R,R′)-fenoterol and analogs to determine their ability to stimulate intracellular cAMP accumulation and inhibit [3H]thymidine incorporation into the cells. 1321N1 cells contain significant levels of β2-AR as determined by receptor binding. (R,R′)-fenoterol and other β2-AR agonists, as well as forskolin, stimulated cAMP accumulation in a dose-dependent manner. Accumulation of cAMP induced a decrease in [3H]thymidine incorporation. There was a correlation between concentration required to stimulate cAMP accumulation and inhibit [3H]thymidine incorporation. U118 cells have a reduced number of β2-ARs and a concomitant reduction in the ability of β2-AR agonists to inhibit cell proliferation. These studies demonstrate the efficacy of β2-AR agonists for inhibition of growth of the astrocytoma cell lines. Because a significant portion of brain tumors contain β2-ARs to a greater extent than whole brain, (R,R′)-fenoterol, or some analog, may be useful in the treatment of brain tumors after biopsy to determine β2-AR expression. PMID:21071556

A brain-penetrant RAF dimer antagonist for the noncanonical BRAF oncoprotein of pediatric low-grade astrocytomas.

PubMed

Sun, Yu; Alberta, John A; Pilarz, Catherine; Calligaris, David; Chadwick, Emily J; Ramkissoon, Shakti H; Ramkissoon, Lori A; Garcia, Veronica Matia; Mazzola, Emanuele; Goumnerova, Liliana; Kane, Michael; Yao, Zhan; Kieran, Mark W; Ligon, Keith L; Hahn, William C; Garraway, Levi A; Rosen, Neal; Gray, Nathanael S; Agar, Nathalie Y; Buhrlage, Sara J; Segal, Rosalind A; Stiles, Charles D

2017-06-01

Activating mutations or structural rearrangements in BRAF are identified in roughly 75% of all pediatric low-grade astrocytomas (PLGAs). However, first-generation RAF inhibitors approved for adult melanoma have poor blood-brain penetrance and are only effective on tumors that express the canonical BRAFV600E oncoprotein, which functions as a monomer. These drugs (type I antagonists that target the "DFG-in" conformation of the kinase) fail to block signaling via KIAA1549:BRAF, a truncation/fusion BRAF oncoprotein which functions as a dimer and is found in the most common form of PLGA. A panel of small molecule RAF inhibitors (including type II inhibitors, targeting the "DFG-out" conformation of the kinase) was screened for drugs showing efficacy on murine models of PLGA and on authentic human PLGA cells expressing KIAA1549:BRAF. We identify a type II RAF inhibitor that serves as an equipotent antagonist of BRAFV600E, KIAA1549:BRAF, and other noncanonical BRAF oncoproteins that function as dimers. This drug (MLN2480, also known as TAK-580) has good brain penetrance and is active on authentic human PLGA cells in brain organotypic cultures. MLN2480 may be an effective therapeutic for BRAF mutant pediatric astrocytomas. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Molecular analysis of pediatric brain tumors identifies microRNAs in pilocytic astrocytomas that target the MAPK and NF-κB pathways.

PubMed

Jones, Tania A; Jeyapalan, Jennie N; Forshew, Tim; Tatevossian, Ruth G; Lawson, Andrew R J; Patel, Sheena N; Doctor, Gabriel T; Mumin, Muhammad A; Picker, Simon R; Phipps, Kim P; Michalski, Antony; Jacques, Thomas S; Sheer, Denise

2015-12-18

Pilocytic astrocytomas are slow-growing tumors that usually occur in the cerebellum or in the midline along the hypothalamic/optic pathways. The most common genetic alterations in pilocytic astrocytomas activate the ERK/MAPK signal transduction pathway, which is a major driver of proliferation but is also believed to induce senescence in these tumors. Here, we have conducted a detailed investigation of microRNA and gene expression, together with pathway analysis, to improve our understanding of the regulatory mechanisms in pilocytic astrocytomas. Pilocytic astrocytomas were found to have distinctive microRNA and gene expression profiles compared to normal brain tissue and a selection of other pediatric brain tumors. Several microRNAs found to be up-regulated in pilocytic astrocytomas are predicted to target the ERK/MAPK and NF-κB signaling pathways as well as genes involved in senescence-associated inflammation and cell cycle control. Furthermore, IGFBP7 and CEBPB, which are transcriptional inducers of the senescence-associated secretory phenotype (SASP), were also up-regulated together with the markers of senescence and inflammation, CDKN1A (p21), CDKN2A (p16) and IL1B. These findings provide further evidence of a senescent phenotype in pilocytic astrocytomas. In addition, they suggest that the ERK/MAPK pathway, which is considered the major driver of these tumors, is regulated not only by genetic aberrations but also by microRNAs.

A tissue microarray study of toll-like receptor 4, decoy receptor 3, and external signal regulated kinase 1/2 expressions in astrocytoma.

PubMed

Lin, Chih-Kung; Ting, Chun-Chieh; Tsai, Wen-Chiuan; Chen, Yuan-Wu; Hueng, Dueng-Yuan

2016-01-01

Decoy receptor 3 (DcR3) functions as a death decoy inhibiting apoptosis mediated by the tumor necrosis factor receptor family. It is highly expressed in many tumors and its expression can be regulated by the MAPK/ERK signaling pathway and ERK is a vital member of this pathway. Toll-like receptor 4 (TLR4) is expressed on immune cells. Increased TLR4 expression has been associated with various types of cancers. The study was conducted to investigate the expression of DcR3, ERK1/2, and TLR4 in astrocytomas and evaluate if they are validating markers for discriminating glioblastoma from anaplastic astrocytoma in limited surgical specimen. Expression of DcR3, ERK1/2, and TLR4 was determined by immunohistochemical staining of tissue microarray from 48 paraffin-embedded tissues. A binary logistic regression method was used to generate functions that discriminate between anaplastic astrocytomas and glioblastomas. The expression of TLR4 and DcR3 was significantly higher in glioblastomas than in anaplastic astrocytomas. DcR3 could discriminate anaplastic astrocytomas from glioblastomas with high sensitivity (93.8%), specificity (90%), and accuracy (92.3%). Our results suggest that DcR3 may be a useful marker for discriminating anaplastic astrocytomas from glioblastomas.

DNA methylation in adult diffuse gliomas.

PubMed

LeBlanc, Veronique G; Marra, Marco A

2016-11-01

Adult diffuse gliomas account for the majority of primary malignant brain tumours, and are in most cases lethal. Current therapies are often only marginally effective, and improved options will almost certainly benefit from further insight into the various processes contributing to gliomagenesis and pathology. While molecular characterization of these tumours classifies them on the basis of genetic alterations and chromosomal abnormalities, DNA methylation patterns are increasingly understood to play a role in glioma pathogenesis. Indeed, a subset of gliomas associated with improved survival is characterized by the glioma CpG island methylator phenotype (G-CIMP), which can be induced by the expression of mutant isocitrate dehydrogenase (IDH1/2). Aberrant methylation of particular genes or regulatory elements, within the context of G-CIMP-positive and/or negative tumours, has also been shown to be associated with differential survival. In this review, we provide an overview of the current knowledge regarding the role of DNA methylation in adult diffuse gliomas. In particular, we discuss IDH mutations and G-CIMP, MGMT promoter methylation, DNA methylation-mediated microRNA regulation and aberrant methylation of specific genes or groups of genes. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Intraarterial Infusion Of Erbitux and Bevacizumab For Relapsed/Refractory Intracranial Glioma In Patients Under 22

ClinicalTrials.gov

2018-01-26

Glioblastoma Multiforme; Fibrillary Astrocytoma of Brain; Glioma of Brainstem; Anaplastic Astrocytoma; Pilomyxoid Astrocytoma; Mixed Oligodendroglioma-Astrocytoma; Brain Stem Glioma; Diffuse Intrinsic Pontine Glioma

Task Inhibition and Response Inhibition in Older vs. Younger Adults: A Diffusion Model Analysis

PubMed Central

Schuch, Stefanie

2016-01-01

Differences in inhibitory ability between older (64–79 years, N = 24) and younger adults (18–26 years, N = 24) were investigated using a diffusion model analysis. Participants performed a task-switching paradigm that allows assessing n−2 task repetition costs, reflecting inhibitory control on the level of tasks, as well as n−1 response-repetition costs, reflecting inhibitory control on the level of responses. N−2 task repetition costs were of similar size in both age groups. Diffusion model analysis revealed that for both younger and older adults, drift rate parameters were smaller in the inhibition condition relative to the control condition, consistent with the idea that persisting task inhibition slows down response selection. Moreover, there was preliminary evidence for task inhibition effects in threshold separation and non-decision time in the older, but not the younger adults, suggesting that older adults might apply different strategies when dealing with persisting task inhibition. N−1 response-repetition costs in mean RT were larger in older than younger adults, but in mean error rates tended to be larger in younger than older adults. Diffusion-model analysis revealed longer non-decision times in response repetitions than response switches in both age groups, consistent with the idea that motor processes take longer in response repetitions than response switches due to persisting response inhibition of a previously executed response. The data also revealed age-related differences in overall performance: Older adults responded more slowly and more accurately than young adults, which was reflected by a higher threshold separation parameter in diffusion model analysis. Moreover, older adults showed larger non-decision times and higher variability in non-decision time than young adults, possibly reflecting slower and more variable motor processes. In contrast, overall drift rate did not differ between older and younger adults. Taken together

Radiation Therapy for Pilocytic Astrocytomas of Childhood

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mansur, David B., E-mail: mansur@radonc.wustl.ed; Rubin, Joshua B.; Kidd, Elizabeth A.

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 initialmore » 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.« less

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.

Comparison of the Diagnostic Accuracy of DSC- and Dynamic Contrast-Enhanced MRI in the Preoperative Grading of Astrocytomas.

PubMed

Nguyen, T B; Cron, G O; Perdrizet, K; Bezzina, K; Torres, C H; Chakraborty, S; Woulfe, J; Jansen, G H; Sinclair, J; Thornhill, R E; Foottit, C; Zanette, B; Cameron, I G

2015-11-01

Dynamic contrast-enhanced MR imaging parameters can be biased by poor measurement of the vascular input function. We have compared the diagnostic accuracy of dynamic contrast-enhanced MR imaging by using a phase-derived vascular input function and "bookend" T1 measurements with DSC MR imaging for preoperative grading of astrocytomas. This prospective study included 48 patients with a new pathologic diagnosis of an astrocytoma. Preoperative MR imaging was performed at 3T, which included 2 injections of 5-mL gadobutrol for dynamic contrast-enhanced and DSC MR imaging. During dynamic contrast-enhanced MR imaging, both magnitude and phase images were acquired to estimate plasma volume obtained from phase-derived vascular input function (Vp_Φ) and volume transfer constant obtained from phase-derived vascular input function (K(trans)_Φ) as well as plasma volume obtained from magnitude-derived vascular input function (Vp_SI) and volume transfer constant obtained from magnitude-derived vascular input function (K(trans)_SI). From DSC MR imaging, corrected relative CBV was computed. Four ROIs were placed over the solid part of the tumor, and the highest value among the ROIs was recorded. A Mann-Whitney U test was used to test for difference between grades. Diagnostic accuracy was assessed by using receiver operating characteristic analysis. Vp_ Φ and K(trans)_Φ values were lower for grade II compared with grade III astrocytomas (P < .05). Vp_SI and K(trans)_SI were not significantly different between grade II and grade III astrocytomas (P = .08-0.15). Relative CBV and dynamic contrast-enhanced MR imaging parameters except for K(trans)_SI were lower for grade III compared with grade IV (P ≤ .05). In differentiating low- and high-grade astrocytomas, we found no statistically significant difference in diagnostic accuracy between relative CBV and dynamic contrast-enhanced MR imaging parameters. In the preoperative grading of astrocytomas, the diagnostic accuracy of dynamic

Subventricular zone predicts high velocity of tumor expansion and poor clinical outcome in patients with low grade astrocytoma.

PubMed

Wen, Bing; Fu, Feixian; Hu, Liangbo; Cai, Qiuyi; Xie, Junshi

2018-05-01

The aim of this study is to clarify the association between subventricular zone (SVZ) involvement and velocity of diametric expansion(VDE) in patients with low-grade astrocytoma and also assessed the clinical outcome of those patients. A total of 168 adult patients with newly diagnosed supratentorial low-grade astrocytoma were studied retrospectively. There were 73 patients had SVZ involvement. Patients with SVZ involvement(7.16 ± 6.53 mm/y) had a higher VDE than patients without SVZ involvement(4.38 ± 5.35 mm/y). VDE was modeled as a categorical variable(＜4, ≥4 and, ＜8, ≥8 and, ＜12, ≥12 mm/y). Logistic regression showed that SVZ involvement was associated with high VDE after adjusting by confounding variables. On the univariate analysis, the results showed that tumor involved with SVZ, VDE ≥ 4 mm/y, VDE ≥ 8 mm/y, and VDE ≥ 8 mm/y were significant predictors of a shorter OS, progression-free survival (PFS) and malignant progression-free survival (MFS)(all p ＜0.05). The categorical variables of VDE (＜4 mm/y, ≥4 mm/y and, ＜8 mm/y, ≥8 mm/y and, ＜12 mm/y, ≥12 mm/y) were adjusted by confounding variables in multivariate analysis, respectively. The results indicated that VDE ≥ 8 mm/y, VDE ≥ 12 mm/y were worse prognostic factors for OS, while VDE ≥ 4 mm/y, VDE ≥ 8 mm/y and VDE ≥ 12 mm/y were related to shorter PFS and MFS. In addition, SVZ involvement was prognostic factors in predicting OS and PFS except MFS. Our results demonstrated that SVZ involvement predicted high VDE and worse clinical outcome, and high VDE was associated with poor prognosis in patients with low-grade astrocytoma. Copyright © 2018 Elsevier B.V. All rights reserved.

Quantitative Proteomics Reveals Fundamental Regulatory Differences in Oncogenic HRAS and Isocitrate Dehydrogenase (IDH1) Driven Astrocytoma.

PubMed

Doll, Sophia; Urisman, Anatoly; Oses-Prieto, Juan A; Arnott, David; Burlingame, Alma L

2017-01-01

Glioblastoma multiformes (GBMs) are high-grade astrocytomas and the most common brain malignancies. Primary GBMs are often associated with disturbed RAS signaling, and expression of oncogenic HRAS results in a malignant phenotype in glioma cell lines. Secondary GBMs arise from lower-grade astrocytomas, have slower progression than primary tumors, and contain IDH1 mutations in over 70% of cases. Despite significant amount of accumulating genomic and transcriptomic data, the fundamental mechanistic differences of gliomagenesis in these two types of high-grade astrocytoma remain poorly understood. Only a few studies have attempted to investigate the proteome, phosphorylation signaling, and epigenetic regulation in astrocytoma. In the present study, we applied quantitative phosphoproteomics to identify the main signaling differences between oncogenic HRAS and mutant IDH1-driven glioma cells as models of primary and secondary GBM, respectively. Our analysis confirms the driving roles of the MAPK and PI3K/mTOR signaling pathways in HRAS driven cells and additionally uncovers dysregulation of other signaling pathways. Although a subset of the signaling changes mediated by HRAS could be reversed by a MEK inhibitor, dual inhibition of MEK and PI3K resulted in more complete reversal of the phosphorylation patterns produced by HRAS expression. In contrast, cells expressing mutant IDH1 did not show significant activation of MAPK or PI3K/mTOR pathways. Instead, global downregulation of protein expression was observed. Targeted proteomic analysis of histone modifications identified significant histone methylation, acetylation, and butyrylation changes in the mutant IDH1 expressing cells, consistent with a global transcriptional repressive state. Our findings offer novel mechanistic insight linking mutant IDH1 associated inhibition of histone demethylases with specific histone modification changes to produce global transcriptional repression in secondary glioblastoma. Our

Management of diffuse low-grade gliomas in adults - use of molecular diagnostics.

PubMed

Buckner, Jan; Giannini, Caterina; Eckel-Passow, Jeanette; Lachance, Daniel; Parney, Ian; Laack, Nadia; Jenkins, Robert

2017-06-01

Diffuse WHO grade II gliomas are histologically and genetically heterogeneous. The 2016 WHO classification redefines grade II gliomas with respect to morphological and molecular tumour alterations: grade II oligodendrogliomas are defined by the presence of whole-arm codeletion in chromosomal arms 1p/19q, whereas isocitrate dehydrogenase (IDH) mutations define subclasses of astrocytoma. Although histological grade remains useful, the prognoses of patients with glioma are more tightly associated with molecular alterations than with grade, and chromosomal and gene array technologies are becoming increasingly beneficial in understanding tumour genetic heterogeneity. The indolent nature of the disease often creates subtle neurological symptoms that can be overlooked or misunderstood, resulting in delayed diagnosis. Seizures often herald the diagnosis, especially in patients who have IDH mutations, which are associated with an increased production of 2-hydroxyglutarate. Treatment paradigms have shifted, owing to new diagnostic criteria and new clinical trial evidence. Patients benefit more from chemoradiation than radiation alone, especially those with tumour IDH1 Arg132His mutations; gross total resection of the tumour, including tumours with IDH mutations, is associated with prolonged survival. Initial observation remains appropriate in patients whose rate of disease growth is not yet completely defined; such patients could include those with completely resected disease and those with 1p/19q codeleted tumours.

The MicroRNA and MessengerRNA Profile of the RNA-Induced Silencing Complex in Human Primary Astrocyte and Astrocytoma Cells

PubMed Central

Moser, Joanna J.; Fritzler, Marvin J.

2010-01-01

Background GW/P bodies are cytoplasmic ribonucleoprotein-rich foci involved in microRNA (miRNA)-mediated messenger RNA (mRNA) silencing and degradation. The mRNA regulatory functions within GW/P bodies are mediated by GW182 and its binding partner hAgo2 that bind miRNA in the RNA-induced silencing complex (RISC). To date there are no published reports of the profile of miRNA and mRNA targeted to the RISC or a comparison of the RISC-specific miRNA/mRNA profile differences in malignant and non-malignant cells. Methodology/Principal Findings RISC mRNA and miRNA components were profiled by microarray analysis of malignant human U-87 astrocytoma cells and its non-malignant counterpart, primary human astrocytes. Total cell RNA as well as RNA from immunoprecipitated RISC was analyzed. The novel findings were fourfold: (1) miRNAs were highly enriched in astrocyte RISC compared to U-87 astrocytoma RISC, (2) astrocytoma and primary astrocyte cells each contained unique RISC miRNA profiles as compared to their respective cellular miRNA profiles, (3) miR-195, 10b, 29b, 19b, 34a and 455-3p levels were increased and the miR-181b level was decreased in U-87 astrocytoma RISC as compared to astrocyte RISC, and (4) the RISC contained decreased levels of mRNAs in primary astrocyte and U-87 astrocytoma cells. Conclusions/Significance The observation that miR-34a and miR-195 levels were increased in the RISC of U-87 astrocytoma cells suggests an oncogenic role for these miRNAs. Differential regulation of mRNAs by specific miRNAs is evidenced by the observation that three miR34a-targeted mRNAs and two miR-195-targeted mRNAs were downregulated while one miR-195-targeted mRNA was upregulated. Biological pathway analysis of RISC mRNA components suggests that the RISC plays a pivotal role in malignancy and other conditions. This study points to the importance of the RISC and ultimately GW/P body composition and function in miRNA and mRNA deregulation in astrocytoma cells and possibly in

The microRNA and messengerRNA profile of the RNA-induced silencing complex in human primary astrocyte and astrocytoma cells.

PubMed

Moser, Joanna J; Fritzler, Marvin J

2010-10-18

GW/P bodies are cytoplasmic ribonucleoprotein-rich foci involved in microRNA (miRNA)-mediated messenger RNA (mRNA) silencing and degradation. The mRNA regulatory functions within GW/P bodies are mediated by GW182 and its binding partner hAgo2 that bind miRNA in the RNA-induced silencing complex (RISC). To date there are no published reports of the profile of miRNA and mRNA targeted to the RISC or a comparison of the RISC-specific miRNA/mRNA profile differences in malignant and non-malignant cells. RISC mRNA and miRNA components were profiled by microarray analysis of malignant human U-87 astrocytoma cells and its non-malignant counterpart, primary human astrocytes. Total cell RNA as well as RNA from immunoprecipitated RISC was analyzed. The novel findings were fourfold: (1) miRNAs were highly enriched in astrocyte RISC compared to U-87 astrocytoma RISC, (2) astrocytoma and primary astrocyte cells each contained unique RISC miRNA profiles as compared to their respective cellular miRNA profiles, (3) miR-195, 10b, 29b, 19b, 34a and 455-3p levels were increased and the miR-181b level was decreased in U-87 astrocytoma RISC as compared to astrocyte RISC, and (4) the RISC contained decreased levels of mRNAs in primary astrocyte and U-87 astrocytoma cells. The observation that miR-34a and miR-195 levels were increased in the RISC of U-87 astrocytoma cells suggests an oncogenic role for these miRNAs. Differential regulation of mRNAs by specific miRNAs is evidenced by the observation that three miR34a-targeted mRNAs and two miR-195-targeted mRNAs were downregulated while one miR-195-targeted mRNA was upregulated. Biological pathway analysis of RISC mRNA components suggests that the RISC plays a pivotal role in malignancy and other conditions. This study points to the importance of the RISC and ultimately GW/P body composition and function in miRNA and mRNA deregulation in astrocytoma cells and possibly in other malignancies.

First-line nitrosourea-based chemotherapy in symptomatic non-resectable supratentorial pure low-grade astrocytomas.

PubMed

Frenay, M P; Fontaine, D; Vandenbos, F; Lebrun, C

2005-09-01

At the present time, there are no proven beneficial effects of chemotherapy (CT) for the treatment of pure low-grade astrocytomas. Brain radiotherapy (RT) still remains the standard treatment in order to reduce or delay tumor progression or symptoms, despite possible long-term neurologic complications. We report 10 patients, with histologically proven pure low-grade fibrillary astrocytomas, to which we administered a first-line nitrosourea-based CT. All patients were symptomatic with pharmaco-resistant epilepsy or neurologic symptoms, and had been rejected for neurosurgical resection. All patients with epilepsy had a clinical improvement with reduction in seizure frequency and 60% became seizure-free. CT was well tolerated; all patients developed myelosuppression with 40% of grade III/IV hematotoxicity. Seven were alive at the time of writing with a mean follow-up of 6.5 years (3.5-12) from first recorded symptoms. The three deceased patients died 7.5, 7.5, and 8.5 years from first symptoms. These results demonstrate that some patients with symptomatic non-resectable fibrillary low-grade astrocytomas can be treated with up-front CT to improve their neurologic status. This report suggests that benefits of CT on symptoms, survival, and quality of life should be prospectively compared with RT.

Diffuse Gliomas for Nonneuropathologists: The New Integrated Molecular Diagnostics.

PubMed

Lee, Sunhee C

2018-05-18

Diffuse gliomas comprise the bulk of "brain cancer" in adults. The recent update to the 4th edition of the World Health Organization's classification of tumors of the central nervous system reflects an unprecedented change in the landscape of the diagnosis and management of diffuse gliomas that will affect all those involved in the management and care of patients. Of the recently discovered gene alterations, mutations in the Krebs cycle enzymes isocitrate dehydrogenases (IDHs) 1 and 2 have fundamentally changed the way the gliomas are understood and classified. Incorporating information on a few genetic parameters (IDH, ATRX and/or p53, and chromosome 1p19q codeletion), a relatively straightforward diagnostic algorithm has been generated with robust and reproducible results that correlate with patients' survival far better than relying on conventional histology alone. Evidence also supports the conclusion that the vast majority of diffuse gliomas without IDH mutations (IDH-wild-type astrocytomas) behave like IDH-wild-type glioblastomas ("molecular GBM"). Together, these changes reflect a big shift in the practice of diagnostic neuropathology in which tumor risk stratification aligns better with molecular information than histology/grading. The purpose of this review is to provide the readers with a brief synopsis of the changes in the 2016 World Health Organization update with an emphasis on diffuse gliomas and to summarize key gene abnormalities on which these classifications are based. Practical points involved in day-to-day diagnostic workup are also discussed, along with a comparison of the various diagnostic tests, including immunohistochemistry, with an emphasis on targeted next-generation sequencing panel technology as a future universal approach.

Nuclear magnetic resonance diagnosis of an anaplastic astrocytoma.

PubMed

Jackson, J A; Derman, H S; Harper, R L; Willcott, M R; Ford, J J; Schneiders, N J; McCrary, J A; Kelly, A; Bryan, R N

1984-01-01

A patient presented with an 8-month history of a progressive left homonymous visual field deficit, left hemiparesis, and a left thalamocortical sensory deficit that was not detectable by repeated conventional neurodiagnostic evaluations. Proton nuclear magnetic resonance (NMR) imaging revealed a right parietal lesion characterized by a prolonged T2 (spin-spin relaxation time). At surgery, the mass proved to be an anaplastic astrocytoma. NMR appears to be more sensitive than x-ray computerized tomography scanning in some patients with malignant gliomas and offers the clinician an additional probe with which to evaluate these patients.

Intracellular tortuosity underlies slow cAMP diffusion in adult ventricular myocytes.

PubMed

Richards, Mark; Lomas, Oliver; Jalink, Kees; Ford, Kerrie L; Vaughan-Jones, Richard D; Lefkimmiatis, Konstantinos; Swietach, Pawel

2016-06-01

3',5'-Cyclic adenosine monophosphate (cAMP) signals in the heart are often confined to concentration microdomains shaped by cAMP diffusion and enzymatic degradation. While the importance of phosphodiesterases (degradative enzymes) in sculpting cAMP microdomains is well established in cardiomyocytes, less is known about cAMP diffusivity (DcAMP) and factors affecting it. Many earlier studies have reported fast diffusivity, which argues against sharply defined microdomains. [cAMP] dynamics in the cytoplasm of adult rat ventricular myocytes were imaged using a fourth generation genetically encoded FRET-based sensor. The [cAMP]-response to the addition and removal of isoproterenol (β-adrenoceptor agonist) quantified the rates of cAMP synthesis and degradation. To obtain a read out of DcAMP, a stable [cAMP] gradient was generated using a microfluidic device which delivered agonist to one half of the myocyte only. After accounting for phosphodiesterase activity, DcAMP was calculated to be 32 µm(2)/s; an order of magnitude lower than in water. Diffusivity was independent of the amount of cAMP produced. Saturating cAMP-binding sites with the analogue 6-Bnz-cAMP did not accelerate DcAMP, arguing against a role of buffering in restricting cAMP mobility. cAMP diffused at a comparable rate to chemically unrelated but similar sized molecules, arguing for a common physical cause of restricted diffusivity. Lower mitochondrial density and order in neonatal cardiac myocytes allowed for faster diffusion, demonstrating the importance of mitochondria as physical barriers to cAMP mobility. In adult cardiac myocytes, tortuosity due to physical barriers, notably mitochondria, restricts cAMP diffusion to levels that are more compatible with microdomain signalling. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.

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

ClinicalTrials.gov

2018-03-07

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

Huge heterogeneity in survival in a subset of adult patients with resected, wild-type isocitrate dehydrogenase status, WHO grade II astrocytomas.

PubMed

Poulen, Gaëtan; Gozé, Catherine; Rigau, Valérie; Duffau, Hugues

2018-04-20

OBJECTIVE World Health Organization grade II gliomas are infiltrating tumors that inexorably progress to a higher grade of malignancy. However, the time to malignant transformation is quite unpredictable at the individual patient level. A wild-type isocitrate dehydrogenase (IDH-wt) molecular profile has been reported as a poor prognostic factor, with more rapid progression and a shorter survival compared with IDH-mutant tumors. Here, the oncological outcomes of a series of adult patients with IDH-wt, diffuse, WHO grade II astrocytomas (AII) who underwent resection without early adjuvant therapy were investigated. METHODS A retrospective review of patients extracted from a prospective database who underwent resection between 2007 and 2013 for histopathologically confirmed, IDH-wt, non-1p19q codeleted AII was performed. All patients had a minimum follow-up period of 2 years. Information regarding clinical, radiographic, and surgical results and survival were collected and analyzed. RESULTS Thirty-one consecutive patients (18 men and 13 women, median age 39.6 years) were included in this study. The preoperative median tumor volume was 54 cm 3 (range 3.5-180 cm 3 ). The median growth rate, measured as the velocity of diametric expansion, was 2.45 mm/year. The median residual volume after surgery was 4.2 cm 3 (range 0-30 cm 3 ) with a median volumetric extent of resection of 93.97% (8 patients had a total or supratotal resection). No patient experienced permanent neurological deficits after surgery, and all patients resumed a normal life. No immediate postoperative chemotherapy or radiation therapy was given. The median clinical follow-up duration from diagnosis was 74 months (range 27-157 months). In this follow-up period, 18 patients received delayed chemotherapy and/or radiotherapy for tumor progression. Five patients (16%) died at a median time from radiological diagnosis of 3.5 years (range 2.6-4.5 years). Survival from diagnosis was 77.27% at 5 years. None of the

Clinical multiplexed exome sequencing distinguishes adult oligodendroglial neoplasms from astrocytic and mixed lineage gliomas.

PubMed

Cryan, Jane B; Haidar, Sam; Ramkissoon, Lori A; Bi, Wenya Linda; Knoff, David S; Schultz, Nikolaus; Abedalthagafi, Malak; Brown, Loreal; Wen, Patrick Y; Reardon, David A; Dunn, Ian F; Folkerth, Rebecca D; Santagata, Sandro; Lindeman, Neal I; Ligon, Azra H; Beroukhim, Rameen; Hornick, Jason L; Alexander, Brian M; Ligon, Keith L; Ramkissoon, Shakti H

2014-09-30

Classifying adult gliomas remains largely a histologic diagnosis based on morphology; however astrocytic, oligodendroglial and mixed lineage tumors can display overlapping histologic features. We used multiplexed exome sequencing (OncoPanel) on 108 primary or recurrent adult gliomas, comprising 65 oligodendrogliomas, 28 astrocytomas and 15 mixed oligoastrocytomas to identify lesions that could enhance lineage classification. Mutations in TP53 (20/28, 71%) and ATRX (15/28, 54%) were enriched in astrocytic tumors compared to oligodendroglial tumors of which 4/65 (6%) had mutations in TP53 and 2/65 (3%) had ATRX mutations. We found that oligoastrocytomas harbored mutations in TP53 (80%, 12/15) and ATRX (60%, 9/15) at frequencies similar to pure astrocytic tumors, suggesting that oligoastrocytomas and astrocytomas may represent a single genetic or biological entity. p53 protein expression correlated with mutation status and showed significant increases in astrocytomas and oligoastrocytomas compared to oligodendrogliomas, a finding that also may facilitate accurate classification. Furthermore our OncoPanel analysis revealed that 15% of IDH1/2 mutant gliomas would not be detected by traditional IDH1 (p.R132H) antibody testing, supporting the use of genomic technologies in providing clinically relevant data. In all, our results demonstrate that multiplexed exome sequencing can support evaluation and classification of adult low-grade gliomas with a single clinical test.

Parietal pilomyxoid astrocytoma with recurrence in 10 months: A case report and review of literature

PubMed Central

Patibandla, Mohana Rao; Thotakura, Amit K.; Uppin, Megha; Challa, Sundaram; Addagada, Gokul Chowdary; Nukavarapu, Manisha

2016-01-01

Pilomyxoid astrocytoma (PMA) is a new entity described in WHO 2007 classification of brain tumors. Pilocytic astrocytoma (PA) and PMA share many histopathological features with a few differences in histopathology and behavior of the tumor. This tumor is commonly located in the hypothalamic chiasmatic region. PMA behaves more aggressively than PA, with shorter progression-free survival as well as a higher rate of recurrence and CNS dissemination. We describe a case of PMA in a 10-year-old male involving left parietal lobe presenting with raised ICP features along with the follow-up. Patient was symptom free after 7 months of postoperative and 5½ months of post-radiation. The unusual site and atypical Magnetic resonance imaging features are distinctive in this case report. PMID:27366287

The fine structure of intracranial neoplasms induced by the inoculation of avian sarcoma virus in neonatal and adult rats.

PubMed Central

Copeland, D. D.; Talley, F. A.; Bigner, D. D.

1976-01-01

Groups of F-344 rats were inoculated with the Bratislava-77 strain of avian sarcoma virus (B-77 ASV) within 24 hours of birth, at 9 days of age, or between 97 and 119 days of age. Intracranial tumors developed in each age group. Multiple tumors with mixed histologic patterns developed in rats inoculated at 1 or 9 days of age. Solitary tumors with a uniform histologic pattern developed in rats inoculated as adults. On the basis of light and electron microscopic study, the majority of tumors in each age group were classified as astrocytomas and divided into either poorly differentiated, gemistocytic, pilocytic, or polymorphic varieties. The polymorphic astrocytomas were most common among neonatally inoculated rats, while the pilocytic astrocytomas were most common among rats inoculated as adults. Ultrastructural characteristics of astrocytes, including gap junctions and 7- to 9-nm filaments, were present in the majority of tumors in each age groups. Astrocytomas induced in adult rats were remarkable for the presence of extensive basement membrane alone the astrocytic cell surfaces. Intracytoplasmic virus-like particles (R particles) were common in the tumor cells. These virus-like particles are morphologically distinct from C-type B-77 ASV, and no morphologic evidence of C-type virus replication was observed in any of the tumors. Images Figure 16 Figure 17 Figure 1 Figure 2 Figure 18 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 Figure 15 PMID:179328

Awake surgery for hemispheric low-grade gliomas: oncological, functional and methodological differences between pediatric and adult populations.

PubMed

Trevisi, Gianluca; Roujeau, Thomas; Duffau, Hugues

2016-10-01

Brain mapping through a direct cortical and subcortical electrical stimulation during an awake craniotomy has gained an increasing popularity as a powerful tool to prevent neurological deficit while increasing extent of resection of hemispheric diffuse low-grade gliomas in adults. However, few case reports or very limited series of awake surgery in children are currently available in the literature. In this paper, we review the oncological and functional differences between pediatric and adult populations, and the methodological specificities that may limit the use of awake mapping in pediatric low-grade glioma surgery. This could be explained by the fact that pediatric low-grade gliomas have a different epidemiology and biologic behavior in comparison to adults, with pilocytic astrocytomas (WHO grade I glioma) as the most frequent histotype, and with WHO grade II gliomas less prone to anaplastic transformation than their adult counterparts. In addition, aside from the issue of poor collaboration of younger children under 10 years of age, some anatomical and functional peculiarities of children developing brain (cortical and subcortical myelination, maturation of neural networks and of specialized cortical areas) can influence direct electrical stimulation methodology and sensitivity, limiting its use in children. Therefore, even though awake procedure with cortical and axonal stimulation mapping can be adapted in a specific subgroup of children with a diffuse glioma from the age of 10 years, only few pediatric patients are nonetheless candidates for awake brain surgery.

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

PubMed Central

Hafez, Raef FA

2007-01-01

Background Low-grade gliomas are uncommon primary brain tumors, located more often in the posterior fossa, optic pathway, and brain stem and less commonly in the cerebral hemispheres. Case presentations Two patients with diagnosed recurrent cystic pilocytic astrocytoma critically located within the brain (thalamic and brain stem) were treated with gamma knife surgery. Gamma knife surgery (GKS) did improve the patient's clinical condition very much which remained stable later on. Progressive reduction on the magnetic resonance imaging (MRI) studies of the solid part of the tumor and almost disappearance of the cystic component was achieved within the follow-up period of 36 months in the first case with the (thalamic located lesion) and 22 months in the second case with the (brain stem located lesion). Conclusion Gamma knife surgery represents an alternate tool in the treatment of recurrent and/or small postoperative residual pilocytic astrocytoma especially if they are critically located PMID:17394660

Anaplastic astrocytoma in the spinal cord of an African pygmy hedgehog (Atelerix albiventris).

PubMed

Gibson, C J; Parry, N M A; Jakowski, R M; Eshar, D

2008-11-01

A 2-year-old, female hedgehog presented with an 8-month history of progressive, ascending paresis/paralysis and was tentatively diagnosed with wobbly hedgehog syndrome. She died awaiting further diagnostic tests, and the owners consented to postmortem examination. Grossly, the bladder was large and flaccid and the cervical and lumbar spinal cord were regionally enlarged, light grey, and friable with multifocal hemorrhages. The thoracic spinal cord was grossly normal. Microscopically all regions of the spinal cord had similar changes, although the cervical and lumbar sections were most severely affected. These regions were completely effaced by a moderately cellular infiltration of highly pleomorphic polygonal to spindle shaped cells, mineralization, and necrosis, which were most consistent with anaplastic astrocytoma. The thoracic spinal cord white matter was similarly infiltrated by the neoplastic cells, with perivascular extension into the otherwise normal grey matter. A diagnosis of anaplastic astrocytoma was confirmed using immunohistochemical stains that were positive for glial fibrillary acidic protein and S100.

Low grade astrocytoma in children under the age of three years: a report from the Canadian pediatric brain tumour consortium.

PubMed

Johnston, Donna L; Keene, Daniel; Bartels, Ute; Carret, Anne-Sophie; Crooks, Bruce; Eisenstat, David D; Fryer, Chris; Lafay-Cousin, Lucie; Larouche, Valerie; Moghrabi, Albert; Wilson, Beverly; Zelcer, Shayna; Silva, Mariana; Bouffet, Eric

2015-08-01

In children under the age of 3 years, the most common solid tumors are brain tumors. Low grade astrocytomas represent 30-40 % of brain tumours in this age group. This study reviewed the incidence, characteristics, therapy, and outcome of children less than 36 months of age diagnosed with a low grade astrocytoma from 1990 to 2005 in Canada. A data bank was established using data collected from Canadian pediatric oncology centers on children less than age 3 diagnosed with brain tumors between 1990 and 2005. Cases of low grade astrocytoma were extracted from this data bank and their characteristics summarized. From the 579 cases in the data bank, 153 cases of low grade astrocytoma (26 %) were identified. The mean duration of symptoms prior to presentation was 13 weeks, and 53 % of patients underwent a greater than 90 % resection of their tumor, while 30 % underwent 10-90 % resection. Seventy-one percent of patients received no further therapy after surgery and of the 45 who received therapy following surgery, 43 received chemotherapy, and 5 received radiation therapy. Sixty-eight patients had recurrence or progression of their tumor. Eighty-seven percent of patients were alive at the time of the survey with a 2 year survival rate of 95.3 ± 1.8 %, 5 year survival rate of 93.1 ± 2.1 % and 10 year survival rate of 89.1 ± 2.8 %. The 5 year survival rate for Canadian children less than 36 months of age with a low grade astrocytoma was 93.0 ± 2.8 % which is similar to that for older children with this tumor.

Promoter hypermethylation of mismatch repair gene hMLH1 predicts the clinical response of malignant astrocytomas to nitrosourea.

PubMed

Fukushima, Takao; Katayama, Yoichi; Watanabe, Takao; Yoshino, Atsuo; Ogino, Akiyoshi; Ohta, Takashi; Komine, Chiaki

2005-02-15

In certain types of human cancers, transcriptional inactivation of hMLH1 by promoter hypermethylation plays a causal role in the loss of mismatch repair functions that modulate cytotoxic pathways in response to DNA-damaging agents. The aim of the present study was to investigate the role of promoter methylation of the hMLH1 gene in malignant astrocytomas. We examined the hMLH1 promoter methylation in a homogeneous cohort of patients with 41 malignant astrocytomas treated by 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-2(2-chloroethyl)-3-nitrosourea chemotherapy in combination with radiation and interferon therapy, and assessed the correlation of such methylation with clinical outcome. hMLH1 promoter methylation was found in 6 (15%) of the 41 newly diagnosed malignant astrocytomas. Hypermethylation of the hMLH1 promoter corresponded closely with a loss of immunohistochemical staining for hMLH1 protein (P = 0.0013). Patients with hMLH1-methylated tumors displayed a greater chance of responding to adjuvant therapy as compared with those with hMLH1-unmethylated tumors (P = 0.0150). The presence of hMLH1 hypermethylation was significantly associated with a longer progression-free survival on both univariate analysis (P = 0.0340) and multivariate analysis (P = 0.0161). The present study identified hMLH1 methylation status as a predictor of the clinical response of malignant astrocytomas to chloroethylnitrosourea-based adjuvant therapy. The findings obtained suggest that determination of the methylation status of hMLH1 could provide a potential basis for designing rational chemotherapeutic strategies, as well as for predicting prognosis.

Adult recurrent pilocytic astrocytoma: Clinical, histopathological and molecular study.

PubMed

Trabelsi, S; Mama, N; Ladib, M; Popov, S; Burford, A; Mokni, M; Tlili, K; Krifa, H; Varella-Garcia, M; Jones, C; Tahar Yacoubi, M; Saad, A; H'mida Ben Brahim, D

2015-12-01

PA is a grade I glial tumor that mostly occurs in children. However, although apparently similar to paediatric PA, adult PA presents a different clinical follow-up that could arise from specific molecular alterations. A variety of genetic alterations have been identified as diagnostic or prognostic glioma molecular markers. We describe a right infratentorial tumor that occurred in a 58-year-old man. Neuroimaging and neuropathological examination suggested PA as an initial diagnosis. The tumor was completely resected. Unexpectedly, two years later, a rapidly growing tumor on the operative site was observed with a second location in the pineal region. Immunohistochemical reactions (IHC), Multiplex ligation probe amplification (MLPA) and fluorescence in situ hybridization (FISH) was performed in both primary and relapse tumor. Neuroimaging and neuropathological examinations suggested an unusual diagnosis for adult patients: a recurrent PA. Both MLPA and FISH analysis contribute to diagnostic confirmation by KIAA1549: BRAF fusion detection. Additional genetic results revealed interesting findings that justified the tumor aggressivity. Molecular analysis of adult PA cases should be routinely combined with histopathological and neuroimaging examination to further refine prognostic diagnoses. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

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

Optic nerve pilomyxoid astrocytoma in a patient with Noonan syndrome.

PubMed

Nair, Sushmita; Fort, John A; Yachnis, Anthony T; Williams, Charles A

2015-06-01

Noonan syndrome (NS; MIM 163950) is an autosomal dominant syndrome which is clinically diagnosed by the distinct facial features, short stature, cardiac anomalies and developmental delay. About 50% of cases are associated with gain of function mutations in PTPN11 gene which leads to activation of the RAS/mitogen-activated protein kinase signaling pathway. This is known to have a role in tumorigenesis. Despite this, only limited reports of solid tumors (Fryssira H, Leventopoulos G, Psoni S, et al. Tumor development in three patients with Noonan syndrome. Eur J Pediatr 2008;167:1025-1031; Schuettpelz LG, McDonald S, Whitesell K et al. Pilocytic astrocytoma in a child with Noonan syndrome. Pediatr Blood Cancer 2009;53:1147-1149; Sherman CB, Ali-Nazir A, Gonzales-Gomez I, et al. Primary mixed glioneuronal tumor of the central nervous system in a patient with Noonan syndrome. J Pediatr Hematol Oncol 2009;31:61-64; Sanford RA, Bowman R, Tomita T, et al. A 16 year old male with Noonan's syndrome develops progressive scoliosis and deteriorating gait. Pediatr Neurosurg 1999;30:47-52) and no prior reports of optic gliomas have been described in patients with NS. We present here a patient with NS with a PTPN11 mutation and an optic pathway pilomyxoid astrocytoma. © 2015 Wiley Periodicals, Inc.

Metrics and textural features of MRI diffusion to improve classification of pediatric posterior fossa tumors.

PubMed

Rodriguez Gutierrez, D; Awwad, A; Meijer, L; Manita, M; Jaspan, T; Dineen, R A; Grundy, R G; Auer, D P

2014-05-01

Qualitative radiologic MR imaging review affords limited differentiation among types of pediatric posterior fossa brain tumors and cannot detect histologic or molecular subtypes, which could help to stratify treatment. This study aimed to improve current posterior fossa discrimination of histologic tumor type by using support vector machine classifiers on quantitative MR imaging features. This retrospective study included preoperative MRI in 40 children with posterior fossa tumors (17 medulloblastomas, 16 pilocytic astrocytomas, and 7 ependymomas). Shape, histogram, and textural features were computed from contrast-enhanced T2WI and T1WI and diffusivity (ADC) maps. Combinations of features were used to train tumor-type-specific classifiers for medulloblastoma, pilocytic astrocytoma, and ependymoma types in separation and as a joint posterior fossa classifier. A tumor-subtype classifier was also produced for classic medulloblastoma. The performance of different classifiers was assessed and compared by using randomly selected subsets of training and test data. ADC histogram features (25th and 75th percentiles and skewness) yielded the best classification of tumor type (on average >95.8% of medulloblastomas, >96.9% of pilocytic astrocytomas, and >94.3% of ependymomas by using 8 training samples). The resulting joint posterior fossa classifier correctly assigned >91.4% of the posterior fossa tumors. For subtype classification, 89.4% of classic medulloblastomas were correctly classified on the basis of ADC texture features extracted from the Gray-Level Co-Occurence Matrix. Support vector machine-based classifiers using ADC histogram features yielded very good discrimination among pediatric posterior fossa tumor types, and ADC textural features show promise for further subtype discrimination. These findings suggest an added diagnostic value of quantitative feature analysis of diffusion MR imaging in pediatric neuro-oncology. © 2014 by American Journal of Neuroradiology.

Veliparib, Radiation Therapy, and Temozolomide in Treating Younger Patients With Newly Diagnosed Diffuse Pontine Gliomas

ClinicalTrials.gov

2018-03-30

Anaplastic Astrocytoma; Brain Stem Glioma; Childhood Mixed Glioma; Fibrillary Astrocytoma; Giant Cell Glioblastoma; Glioblastoma; Gliosarcoma; Untreated Childhood Anaplastic Astrocytoma; Untreated Childhood Brain Stem Glioma; Untreated Childhood Fibrillary Astrocytoma; Untreated Childhood Giant Cell Glioblastoma; Untreated Childhood Glioblastoma; Untreated Childhood Gliosarcoma

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

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

PubMed Central

Dam, A.; Fock, J. M.; Hayes, V. M.; Molenaar, W. M.; van den Berg, E.

2000-01-01

An 8-year-old girl presented with a cerebral tumor and 3 recurrences within 15 months. The primary tumor was a low-grade astrocytoma, but the recurrences showed progressively malignant phenotypes with increasing mitotic activity and MIB-1 labeling indices. Radiotherapy was given between the first and the second recurrences. Cytogenetic analysis of the first and the second recurrences showed abnormal karyotypes. There seemed to be 2 common breakpoints in these 2 recurrences. TP53 gene mutation screening, using comprehensive denaturing gradient gel electrophoresis, revealed among others a possibly causative mutation of exon 5 in 3 of 4 tumor samples. The meaning of TP53 mutations in low-grade astrocytomas is still unclear, but the highly abnormal karyotypes, which are unusual in these tumors, probably provide genetic evidence for the unexpected aggressive behavior of the tumor in this patient. PMID:11302339

Extent of resection and timing of surgery in adult low grade glioma.

PubMed

A Mirza, Farhan; Shamim, Muhammad Shahzad

2017-06-01

Low grade glioma is a group of WHO grade II tumours including diffuse astrocytoma, oligodendroglioma, and oligoastrocytoma. Strong evidence exists in literature now to support early surgery and higher extent of safe resection in improving outcomes. In this review, we are highlighting some of the important studies done in the last few years specifically addressing timing of surgery and extent of resection.

Preliminary individualized chemotherapy for malignant astrocytomas based on O6-methylguanine-deoxyribonucleic acid methyltransferase methylation analysis.

PubMed

Watanabe, Takao; Katayama, Yoichi; Ogino, Akiyoshi; Ohta, Takashi; Yoshino, Atsuo; Fukushima, Takao

2006-08-01

O(6)-methylguanine-deoxyribonucleic acid methyltransferase gene (MGMT) methylation is apparently correlated with responsiveness to nitrosourea chemotherapy, suggesting this alkylating agent should be effective against MGMT-methylated tumors. MGMT appears not to be linked to platinum resistance, so platinum chemotherapy should be used for MGMT-unmethylated tumors. This study was a preliminary trial of individualized chemotherapy based on MGMT methylation status in a total of 20 patients with newly diagnosed malignant astrocytomas (9 anaplastic astrocytomas and 11 glioblastomas multiforme). The procarbazine, 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-2(2-chloroethyl)-3-nitrosourea, and vincristine (PAV) regimen was administered to seven patients with MGMT-methylated tumors, and the carboplatin and etoposide (CE) regimen was administered to 13 patients with MGMT-unmethylated tumors. Objective response to the PAV therapy was noted in all three patients with measurable residual tumor (2 complete responses and 1 partial response). Five of the seven patients continued to be disease-free after initiation of the PAV therapy. Objective response to the CE therapy was seen in only one of seven patients with measurable residual tumor (1 partial response). Three of the 13 patients were free from progression, whereas the remaining 10 patients showed early progression. The PAV regimen is effective against MGMT-methylated malignant astrocytomas, but the CE regimen is not useful at the given dose and schedule in MGMT-unmethylated tumors.

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.

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

Reference values for pulmonary diffusing capacity for adult native Finns.

PubMed

Kainu, Annette; Toikka, Jyri; Vanninen, Esko; Timonen, Kirsi L

2017-04-01

Measurement standards for pulmonary diffusing capacity were updated in 2005 by the ATS/ERS Task Force. However, in Finland reference values published in 1982 by Viljanen et al. have been used to date. The main aim of this study was to produce updated reference models for single-breath diffusing capacity for carbon monoxide for Finnish adults. Single-breath diffusing capacity for carbon monoxide was measured in 631 healthy non-smoking volunteers (41.5% male). Reference values for diffusing capacity (DLCO), alveolar volume (VA), diffusing capacity per unit of lung volume (DLCO/VA), and lung volumes were calculated using a linear regression model. Previously used Finnish reference values were found to produce too low predicted values, with mean predicted DLCO 111.0 and 104.4%, and DLCO/VA of 103.5 and 102.7% in males and females, respectively. With the European Coalition for Steel and Coal (ECSC) reference values there was a significant sex difference in DLCO/VA with mean predicted 105.4% in males and 92.8% in females (p < .001). New reference values for DLCO, DLCO/VA, VA, vital capacity (VC), inspiratory vital capacity (IVC), and inspiratory capacity (IC) are suggested for clinical use to replace technically outdated reference values for clinical applications.

AGGRESSIVE RETINAL ASTROCYTOMAS IN FOUR PATIENTS WITH TUBEROUS SCLEROSIS COMPLEX

PubMed Central

Shields, Jerry A; Eagle, Ralph C; Shields, Carol L; Marr, Brian P

2004-01-01

ABSTRACT Objective To report the clinical and histopathologic findings of retinal astrocytic tumors that showed progressive growth in four patients with tuberous sclerosis complex (TSC). Methods Four young children each developed an enlarging retinal neoplasm that eventually necessitated enucleation of the affected eye. The systemic findings, clinical course, and histopathologic findings were reviewed. Results Each patient had a progressively enlarging retinal mass associated with a total exudative retinal detachment and neovascular glaucoma. Enucleation was necessary in each case because the affected eye became blind and painful. The mean patient age at enucleation was 7 years, and the median age was 3 years. At the time of enucleation the tumors ranged from 10 to 20 mm in basal diameter and from 10 to 25 mm in thickness. Histopathologic studies of each eye revealed a giant cell astrocytoma that had produced a total exudative retinal detachment. The tumor cells showed positive immunoreactivity to neuron-specific enolase and glial fibrillary acidic protein. The retinal neoplasms in these cases were identical histopathologically to the subependymal giant cell astrocytoma that typifies TSC in the brain. One tumor filled the entire eye and perforated the globe. Although the lesions simulated retinoblastoma clinically, each patient had ocular and systemic findings of TSC, supporting the diagnosis of astrocytic hamartoma. Conclusions Although retinal astrocytic lesions of TSC generally are stationary, they can sometimes grow relentlessly and cause severe ocular complications. Patients with retinal astrocytic hamartomas should have serial ophthalmic evaluations because of this possibility. PMID:15747752

Diffusion-tensor imaging of white matter tracts in patients with cerebral neoplasm.

PubMed

Witwer, Brian P; Moftakhar, Roham; Hasan, Khader M; Deshmukh, Praveen; Haughton, Victor; Field, Aaron; Arfanakis, Konstantinos; Noyes, Jane; Moritz, Chad H; Meyerand, M Elizabeth; Rowley, Howard A; Alexander, Andrew L; Badie, Behnam

2002-09-01

Preserving vital cerebral function while maximizing tumor resection is a principal goal in surgical neurooncology. Although functional magnetic resonance imaging has been useful in the localization of eloquent cerebral cortex, this method does not provide information about the white matter tracts that may be involved in invasive, intrinsic brain tumors. Recently, diffusion-tensor (DT) imaging techniques have been used to map white matter tracts in the normal brain. The aim of this study was to demonstrate the role of DT imaging in preoperative mapping of white matter tracts in relation to cerebral neoplasms. Nine patients with brain malignancies (one pilocytic astrocytoma, five oligodendrogliomas, one low-grade oligoastrocytoma, one Grade 4 astrocytoma, and one metastatic adenocarcinoma) underwent DT imaging examinations prior to tumor excision. Anatomical information about white matter tract location, orientation, and projections was obtained in every patient. Depending on the tumor type and location, evidence of white matter tract edema (two patients), infiltration (two patients), displacement (five patients), and disruption (two patients) could be assessed with the aid of DT imaging in each case. Diffusion-tensor imaging allowed for visualization of white matter tracts and was found to be beneficial in the surgical planning for patients with intrinsic brain tumors. The authors' experience with DT imaging indicates that anatomically intact fibers may be present in abnormal-appearing areas of the brain. Whether resection of these involved fibers results in subtle postoperative neurological deficits requires further systematic study.

Investigating task inhibition in children versus adults: A diffusion model analysis.

PubMed

Schuch, Stefanie; Konrad, Kerstin

2017-04-01

One can take n-2 task repetition costs as a measure of inhibition on the level of task sets. When switching back to a Task A after only one intermediate trial (ABA task sequence), Task A is thought to still be inhibited, leading to performance costs relative to task sequences where switching back to Task A is preceded by at least two intermediary trials (CBA). The current study investigated differences in inhibitory ability between children and adults by comparing n-2 task repetition costs in children (9-11years of age, N=32) and young adults (21-30years of age, N=32). The mean reaction times and error rate differences between ABA and CBA sequences did not differ between the two age groups. However, diffusion model analysis revealed that different cognitive processes contribute to the inhibition effect in the two age groups: The adults, but not the children, showed a smaller drift rate in ABA than in CBA, suggesting that persisting task inhibition is associated with slower response selection in adults. In children, non-decision time was longer in ABA than in CBA, possibly reflecting longer task preparation in ABA than in CBA. In addition, Ex-Gaussian functions were fitted to the distributions of correct reaction times. In adults, the ABA-CBA difference was reflected in the exponential parameter of the distribution; in children, the ABA-CBA difference was found in the Gaussian mu parameter. Hence, Ex-Gaussian analysis, although noisier, was generally in line with diffusion model analysis. Taken together, the data suggest that the task inhibition effect found in mean performance is mediated by different cognitive processes in children versus adults. Copyright © 2016 Elsevier Inc. All rights reserved.

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

Expression of pERK and pAKT in human astrocytomas: correlation with IDH1-R132H presence, vascular endothelial growth factor, microvascular characteristics and clinical outcome.

PubMed

Saetta, Angelica A; Levidou, Georgia; El-Habr, Elias A; Panayotidis, Ioannis; Samaras, Vassilis; Thymara, Irene; Sakellariou, Stratigoula; Boviatsis, Efstathios; Patsouris, Efstratios; Korkolopoulou, Penelope

2011-06-01

Although pERK and pAKT are reportedly activated in various neoplasms, little information is available about their significance in astrocytomas. Paraffin-embedded tissue from 82 patients with diffuse infiltrating astrocytomas (grades II to IV) was investigated for the association of pERK and pAKT activation with clinicopathological features, vascular endothelial growth factor (VEGF), isocitrate dehydrogenase 1 and microvascular parameters. Nuclear pERK labelling index (LI) increased with increasing cytoplasmic pERK LI and nuclear and cytoplasmic pAKT LI (p = 0.0019, p = 0.0260 and p = 0.0012, respectively). Accordingly, cytoplasmic pERK increased with increasing levels of nuclear (p = 0.0001) and marginally with cytoplasmic pAKT LI (p = 0.0526). Nuclear and cytoplasmic pERK LI and nuclear pAKT LI were positively correlated with tumour histological grade (p = 0.0040, p = 0.0238 for pERK and p = 0.0004 for pAKT, respectively). VEGF expression was correlated with nuclear pERK (p = 0.0099) and nuclear pAKT LI (p = 0.0002). Interestingly, pERK cytoplasmic LI increased with microvessel calibre (p = 0.0287), whereas pAKT nuclear LI was marginally related to microvessel density (p = 0.0685). The presence of IDH1-R132H was related only to histological grade and lower microvessel calibre. Multivariate survival analysis in the entire cohort selected cytoplasmic pAKT LI (p = 0.045), histological grade, microvessel calibre (p = 0.028), patients' age, gender and surgical excision as independent predictors of survival. Moreover, in glioblastomas, pERK nuclear LI emerged as a favourable prognosticator in the presence of IDH1-R132H. pERK and pAKT in astrocytomas are interrelated and associated with tumour grade and angiogenesis. Moreover, the importance of cytoplasmic pAKT immunoexpression in patients' prognosis and nuclear pERK immunoexpression in glioblastomas is confirmed.

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

A Diffusion Model Analysis of Adult Age Differences in Episodic and Semantic Long-Term Memory Retrieval

ERIC Educational Resources Information Center

Spaniol, Julia; Madden, David J.; Voss, Andreas

2006-01-01

Two experiments investigated adult age differences in episodic and semantic long-term memory tasks, as a test of the hypothesis of specific age-related decline in context memory. Older adults were slower and exhibited lower episodic accuracy than younger adults. Fits of the diffusion model (R. Ratcliff, 1978) revealed age-related increases in…

[The heterogeneity of blood flow on magnetic resonance imaging: a biomarker for grading cerebral astrocytomas].

PubMed

Revert Ventura, A J; Sanz Requena, R; Martí-Bonmatí, L; Pallardó, Y; Jornet, J; Gaspar, C

2014-01-01

To study whether the histograms of quantitative parameters of perfusion in MRI obtained from tumor volume and peritumor volume make it possible to grade astrocytomas in vivo. We included 61 patients with histological diagnoses of grade II, III, or IV astrocytomas who underwent T2*-weighted perfusion MRI after intravenous contrast agent injection. We manually selected the tumor volume and peritumor volume and quantified the following perfusion parameters on a voxel-by-voxel basis: blood volume (BV), blood flow (BF), mean transit time (TTM), transfer constant (K(trans)), washout coefficient, interstitial volume, and vascular volume. For each volume, we obtained the corresponding histogram with its mean, standard deviation, and kurtosis (using the standard deviation and kurtosis as measures of heterogeneity) and we compared the differences in each parameter between different grades of tumor. We also calculated the mean and standard deviation of the highest 10% of values. Finally, we performed a multiparametric discriminant analysis to improve the classification. For tumor volume, we found statistically significant differences among the three grades of tumor for the means and standard deviations of BV, BF, and K(trans), both for the entire distribution and for the highest 10% of values. For the peritumor volume, we found no significant differences for any parameters. The discriminant analysis improved the classification slightly. The quantification of the volume parameters of the entire region of the tumor with BV, BF, and K(trans) is useful for grading astrocytomas. The heterogeneity represented by the standard deviation of BF is the most reliable diagnostic parameter for distinguishing between low grade and high grade lesions. Copyright © 2011 SERAM. Published by Elsevier Espana. All rights reserved.

FGFR1 tyrosine kinase domain duplication in pilocytic astrocytoma with anaplasia

PubMed Central

Ballester, Leomar Y.; Penas-Prado, Marta; Leeds, Norman E.; Huse, Jason T.; Fuller, Gregory N.

2018-01-01

We report the case of a 27-yr-old male with visual field loss who had a 4.9-cm complex cystic mass in the right occipital lobe. Histologic examination showed pilocytic astrocytoma (PA) with anaplasia, and molecular characterization revealed FGFR1 duplication with additional variants of unknown significance in several genes (ARID1A, ARID1B, CHEK2, EPHA5, and MLL2). This is one of only a very few reported cases of anaplastic PA with characterization of molecular alterations. PMID:29610389

White matter integrity in Asperger syndrome: a preliminary diffusion tensor magnetic resonance imaging study in adults.

PubMed

Bloemen, Oswald J N; Deeley, Quinton; Sundram, Fred; Daly, Eileen M; Barker, Gareth J; Jones, Derek K; van Amelsvoort, Therese A M J; Schmitz, Nicole; Robertson, Dene; Murphy, Kieran C; Murphy, Declan G M

2010-10-01

Autistic Spectrum Disorder (ASD), including Asperger syndrome and autism, is a highly genetic neurodevelopmental disorder. There is a consensus that ASD has a biological basis, and it has been proposed that it is a "connectivity" disorder. Diffusion Tensor Magnetic Resonance Imaging (DT-MRI) allows measurement of the microstructural integrity of white matter (a proxy measure of "connectivity"). However, nobody has investigated the microstructural integrity of whole brain white matter in people with Asperger syndrome. We measured the fractional anisotropy (FA), mean diffusivity (MD) and radial diffusivity (RD) of white matter, using DT-MRI, in 13 adults with Asperger syndrome and 13 controls. The groups did not differ significantly in overall intelligence and age. FA, MD and RD were assessed using whole brain voxel-based techniques. Adults with Asperger syndrome had a significantly lower FA than controls in 13 clusters. These were largely bilateral and included white matter in the internal capsule, frontal, temporal, parietal and occipital lobes, cingulum and corpus callosum. Adults with Asperger syndrome have widespread significant differences from controls in white matter microstructural integrity.

Diffuse intrinsic pontine gliomas in children: Interest of robotic frameless assisted biopsy. A technical note.

PubMed

Coca, H A; Cebula, H; Benmekhbi, M; Chenard, M P; Entz-Werle, N; Proust, F

2016-12-01

Diffuse intrinsic pontine gliomas (DIPG) constitute 10-15% of all brain tumors in the pediatric population; currently prognosis remains poor, with an overall survival of 7-14 months. Recently the indication of DIPG biopsy has been enlarged due to the development of molecular biology and various ongoing clinical and therapeutic trials. Classically a biopsy is performed using a stereotactic frame assisted procedure but the workflow may sometimes be heavy and more complex especially in children. In this study the authors present their experience with frameless robotic-guided biopsy of DIPG in a pediatric population. Retrospective study on a series of five consecutive pediatric patients harboring DIPG treated over a 4-year period. All patients underwent frameless robotic-guided biopsy via a transcerebellar approach. Among the 5 patients studied 3 were male and 2 female with a median age of 8.6 years [range 5 to 13 years]. Clinical presentation included ataxia, hemiparesis and cranial nerve palsy in all patients. MRI imaging of the lesion showed typical DIPG features (3 of them located in the pons) with hypo-intensity on T1 and hyper-intensity signal on T2 sequences and diffuse gadolinium enhancement. The mean procedure time was 56minutes (range 45 to 67minutes). No new postoperative neurological deficits were recorded. Histological diagnosis was achieved in all cases as follows: two anaplastic astrocytomas (grade III), two glioblastomas, and one diffuse astrocytoma (grade III). Frameless robotic assisted biopsy of DIPG in pediatric population is an easier, effective, safe and highly accurate method to achieve diagnosis. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

A pediatric trial of radiation/cetuximab followed by irinotecan/cetuximab in newly diagnosed diffuse pontine gliomas and high-grade astrocytomas: A Pediatric Oncology Experimental Therapeutics Investigators' Consortium study.

PubMed

Macy, Margaret E; Kieran, Mark W; Chi, Susan N; Cohen, Kenneth J; MacDonald, Tobey J; Smith, Amy A; Etzl, Michael M; Kuei, Michele C; Donson, Andrew M; Gore, Lia; DiRenzo, Jennifer; Trippett, Tanya M; Ostrovnaya, Irina; Narendran, Aru; Foreman, Nicholas K; Dunkel, Ira J

2017-11-01

Diffuse intrinsic pontine gliomas (DIPGs) and high-grade astrocytomas (HGA) continue to have dismal prognoses. The combination of cetuximab and irinotecan was demonstrated to be safe and tolerable in a previous pediatric phase 1 combination study. We developed this phase 2 trial to investigate the safety and efficacy of cetuximab given with radiation therapy followed by adjuvant cetuximab and irinotecan. Eligible patients of age 3-21 years had newly diagnosed DIPG or HGA. Patients received radiation therapy (5,940 cGy) with concurrent cetuximab. Following radiation, patients received cetuximab weekly and irinotecan daily for 5 days per week for 2 weeks every 21 days for 30 weeks. Correlative studies were performed. The regimen was considered to be promising if the number of patients with 1-year progression-free survival (PFS) for DIPG and HGA was at least six of 25 and 14 of 26, respectively. Forty-five evaluable patients were enrolled (25 DIPG and 20 HGA). Six patients with DIPG and five with HGA were progression free at 1 year from the start of therapy with 1-year PFS of 29.6% and 18%, respectively. Fatigue, gastrointestinal complaints, electrolyte abnormalities, and rash were the most common adverse events and generally of grade 1 and 2. Increased epidermal growth factor receptor copy number but no K-ras mutations were identified in available samples. The trial did not meet the predetermined endpoint to deem this regimen successful for HGA. While the trial met the predetermined endpoint for DIPG, overall survival was not markedly improved from historical controls, therefore does not merit further study in this population. © 2017 Wiley Periodicals, Inc.

FGFR1 tyrosine kinase domain duplication in pilocytic astrocytoma with anaplasia.

PubMed

Ballester, Leomar Y; Penas-Prado, Marta; Leeds, Norman E; Huse, Jason T; Fuller, Gregory N

2018-04-01

We report the case of a 27-yr-old male with visual field loss who had a 4.9-cm complex cystic mass in the right occipital lobe. Histologic examination showed pilocytic astrocytoma (PA) with anaplasia, and molecular characterization revealed FGFR1 duplication with additional variants of unknown significance in several genes ( ARID1A, ARID1B, CHEK2, EPHA5, and MLL2 ). This is one of only a very few reported cases of anaplastic PA with characterization of molecular alterations. © 2018 Ballester et al.; Published by Cold Spring Harbor Laboratory Press.

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.

Low expression of p27 indicates a poor prognosis in patients with high-grade astrocytomas.

PubMed

Kirla, Ruut M; Haapasalo, Hannu K; Kalimo, Hannu; Salminen, Eeva K

2003-02-01

Two families of tumor suppressor genes, Cip/Kip (p21, p27, and 57) and INK4 (p15, p16, p18, and p19), regulate cell proliferation and neoplastic transformation. p27 exerts its suppressor effect through cyclin E-dependent kinase (CDK2) by inhibiting the phosphorylation of pRb by CDK2, which, in turn, arrests cells in the G1-phase. p21 has a similar effect in addition to participating in the p53 dependent CDK4-mediated and CDK6-mediated pathway. The authors studied the prognostic significance of p21 and p27 in patients with high-grade astrocytomas who were treated with radiotherapy. The expression of p27 and p21 was analyzed immunohistochemically in 52 glioblastomas and 25 anaplastic astrocytomas. All patients underwent surgery for the first time and were treated with adjuvant external radiotherapy. The p27 labeling index (LI) was < 30% in 36% of tumors, 30-50% in 25% of tumors, and > 50% in 39% of tumors. A significant difference in cumulative survival was observed between these groups (P = 0.0072; log-rank test). The p21 LI was < 30% in 48% of tumors, 30-50% in 39% of tumors, and > 50% in 13% of tumors; these groups did not differ significantly in survival. In multivariate Cox analysis, p27 LI was an independent prognostic factor (P = 0.0008). The grade of malignancy and proliferation activity also were independent prognostic factors. Although p27 and p21 are parallel cell-cycle regulators, only p27 has independent prognostic value in patients with malignant astrocytomas. It appears that decreased levels of p21/p27 are associated with a poor prognosis and short survival. Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11079

Adult Instructors' Perceptions on ICT and Diffusion Practices: Implications for Equity of Access

ERIC Educational Resources Information Center

Salinas-Amescua, Bertha

2007-01-01

This study suggests equity of access goes beyond technological availability. Based on a larger exploratory study of the initial implementation stage of the Mexican government's community technology centers, CTCs ("plazas comunitarias"), adult education instructors' perceptions and diffusion practices are described as a mediating factor…

Insight from uncertainty: bootstrap-derived diffusion metrics differentially predict memory function among older adults.

PubMed

Vorburger, Robert S; Habeck, Christian G; Narkhede, Atul; Guzman, Vanessa A; Manly, Jennifer J; Brickman, Adam M

2016-01-01

Diffusion tensor imaging suffers from an intrinsic low signal-to-noise ratio. Bootstrap algorithms have been introduced to provide a non-parametric method to estimate the uncertainty of the measured diffusion parameters. To quantify the variability of the principal diffusion direction, bootstrap-derived metrics such as the cone of uncertainty have been proposed. However, bootstrap-derived metrics are not independent of the underlying diffusion profile. A higher mean diffusivity causes a smaller signal-to-noise ratio and, thus, increases the measurement uncertainty. Moreover, the goodness of the tensor model, which relies strongly on the complexity of the underlying diffusion profile, influences bootstrap-derived metrics as well. The presented simulations clearly depict the cone of uncertainty as a function of the underlying diffusion profile. Since the relationship of the cone of uncertainty and common diffusion parameters, such as the mean diffusivity and the fractional anisotropy, is not linear, the cone of uncertainty has a different sensitivity. In vivo analysis of the fornix reveals the cone of uncertainty to be a predictor of memory function among older adults. No significant correlation occurs with the common diffusion parameters. The present work not only demonstrates the cone of uncertainty as a function of the actual diffusion profile, but also discloses the cone of uncertainty as a sensitive predictor of memory function. Future studies should incorporate bootstrap-derived metrics to provide more comprehensive analysis.

Children Are Not like Older Adults: A Diffusion Model Analysis of Developmental Changes in Speeded Responses

ERIC Educational Resources Information Center

Ratcliff, Roger; Love, Jessica; Thompson, Clarissa A.; Opfer, John E.

2012-01-01

Children (n = 130; M[subscript age] = 8.51-15.68 years) and college-aged adults (n = 72; M[subscript age] = 20.50 years) completed numerosity discrimination and lexical decision tasks. Children produced longer response times (RTs) than adults. R. Ratcliff's (1978) diffusion model, which divides processing into components (e.g., quality of…

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

PubMed

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

2015-01-01

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. We evaluated 20 SNPs of 703 glioma cases (338 astrocytoma cases, 122 glioblastoma cases) and 635 controls in a Han Chinese population using χ(2) test and genetic model analysis. 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). 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.

Safety and efficacy of high-dose chemotherapy with autologous stem cell transplantation for patients with malignant astrocytomas.

PubMed

Chen, Benjamin; Ahmed, Tauseef; Mannancheril, Anney; Gruber, Michael; Benzil, Deborah L

2004-05-15

Malignant astrocytomas are among the most resistant tumors to curative treatments. Mean survival without treatment is measured in weeks, and even with maximal surgery and radiation, the mean reported survival is < 1 year. The advent of supportive treatments and newer agents has resulted in benefits for many patients with cancer. The authors investigated the safety and effect on survival of a high-dose thiotepa and carboplatin regimen with autologous stem cell transplantation (ASCT) in patients with malignant astrocytomas who were enrolled in a prospective trial approved by an institutional review board (IRB). Twenty-one patients were enrolled in an IRB-approved, prospective trial. After baseline testing was completed, patients underwent peripheral stem cell mobilization with cyclophosphamide (4 g/m2) and etoposide (450 mg/m2) followed by granulocyte-colony-stimulating factor (10 microg/kg). Peripheral stem cells were harvested when leukocyte counts recovered. Patients received 2 cycles of thiotepa (750 mg/m2) and carboplatin (1600 mg/m2) followed by infusion of the preserved stem cells. The cycles were administered 6-10 weeks apart. Primary outcome measures were patient survival (Kaplan-Meier analysis) and treatment toxicity (using National Cancer Institute common toxicity criteria). Autologous stem cells were harvested effectively and transfused in all patients. Kaplan-Meier survival analysis demonstrated a survival time of 34.3 +/- 5.5 months (range, 9-94 months). Despite significant myelosuppression, only three patients experienced Grade 4 complications and eight experienced Grade 3 complications. High-dose chemotherapy with thiotepa and carboplatin with concomitant ASCT was used safely to treat patients with malignant astrocytomas and may provide a survival advantage. Copyright 2004 American Cancer Society.

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…

Pion radiation for high grade astrocytoma: results of a randomized study.

PubMed

Pickles, T; Goodman, G B; Rheaume, D E; Duncan, G G; Fryer, C J; Bhimji, S; Ludgate, C; Syndikus, I; Graham, P; Dimitrov, M; Bowen, J

1997-02-01

This study attempted to compare within a randomized study the outcome of pion radiation therapy vs. conventional photon irradiation for the treatment of high-grade astrocytomas. Eighty-four patients were randomized to pion therapy (33-34.5 Gy pi), or conventional photon irradiation (60 Gy). Entry criteria included astrocytoma (modified Kernohan high Grade 3 or Grade 4), age 18-70, Karnofsky performance status (KPS) > or = 50, ability to start irradiation within 30 days of surgery, unifocal tumor, and treatment volume < 850 cc. The high-dose volume in both arms was computed tomography enhancement plus a 2-cm margin. The study was designed with the power to detect a twofold difference between arms. Eighty-one eligible patients were equally balanced for all known prognostic variables. Pion patients started radiation 7 days earlier on average than photon patients, but other treatment-related variables did not differ. There were no significant differences for either early or late radiation toxicity between treatment arms. Actuarial survival analysis shows no differences in terms of time to local recurrence or overall survival where median survival was 10 months in both arms (p = 0.22). The physician-assessed KPS and patient-assessed quality of life (QOL) measurements were generally maintained within 10 percentage points until shortly before tumor recurrence. There was no apparent difference in the serial KPS or QOL scores between treatment arms. In contrast to high linear energy transfer (LET) therapy for central nervous system tumors, such as neutron or neon therapy, the safety of pion therapy, which is of intermediate LET, has been reaffirmed. However, this study has demonstrated no therapeutic gain for pion therapy of glioblastoma.

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

Diffusion tensor spectroscopic imaging of the human brain in children and adults.

PubMed

Fotso, Kevin; Dager, Stephen R; Landow, Alec; Ackley, Elena; Myers, Orrin; Dixon, Mindy; Shaw, Dennis; Corrigan, Neva M; Posse, Stefan

2017-10-01

We developed diffusion tensor spectroscopic imaging (DTSI), based on proton-echo-planar-spectroscopic imaging (PEPSI), and evaluated the feasibility of mapping brain metabolite diffusion in adults and children. PRESS prelocalized DTSI at 3 Tesla (T) was performed using navigator-based correction of movement-related phase errors and cardiac gating with compensation for repetition time (TR) related variability in T 1 saturation. Mean diffusivity (MD) and fractional anisotropy (FA) of total N-acetyl-aspartate (tNAA), total creatine (tCr), and total choline (tCho) were measured in eight adults (17-60 years) and 10 children (3-24 months) using b max  = 1734 s/mm 2 , 1 cc and 4.5 cc voxel sizes, with nominal scan times of 17 min and 8:24 min. Residual movement-related phase encoding ghosting (PEG) was used as a regressor across scans to correct overestimation of MD. After correction for PEG, metabolite slice-averaged MD estimated at 20% PEG were lower (P < 0.042) for adults (0.17/0.20/0.18 × 10 -3 mm 2 /s) than for children (0.26/0.27/0.24 × 10 -3 mm 2 /s). Extrapolated to 0% PEG, the MD estimates decreased further (0.09/0.11/0.11 × 10 -3 mm 2 /s versus 0.15/0.16/0.15 × 10 -3 mm 2 /s). Slice-averaged FA of tNAA (P = 0.049), tCr (P = 0.067), and tCho (P = 0.003) were higher in children. This high-speed DTSI approach with PEG regression allows for estimation of metabolite MD and FA with improved tolerance to movement. Our preliminary data suggesting age-related changes support DTSI as a sensitive technique for investigating intracellular markers of biological processes. Magn Reson Med 78:1246-1256, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

c-erbB-2 in astrocytomas: infrequent overexpression by immunohistochemistry and absence of gene amplification by fluorescence in situ hybridization.

PubMed Central

Haapasalo, H.; Hyytinen, E.; Sallinen, P.; Helin, H.; Kallioniemi, O. P.; Isola, J.

1996-01-01

Recent studies suggest that aberrations of c-erbB-2 may be involved in astrocytic brain tumours. We screened immunohistochemically c-erbB2 protein (p185) expression in 94 astrocytic grade 1-4 neoplasms of the brain. The amplification of the c-erbB-2 oncogene was investigated in protein overexpression cases by dual colour fluorescence in situ hybridisation (FISH). p185 overexpression was correlated with p53 and epidermal growth factor receptor (EGFR) expression, as well as with clinicopathological features. Only two anaplastic (grade 3) astrocytomas and one glioblastoma (grade 4) showed overexpression of p185 protein by immunohistochemistry (monoclonal MAb1 antibody TA250), whereas none of the grade 1-2 astrocytomas was positive. Interestingly, the expression of p185 was confined solely to the cytoplasm of neoplastic astrocytic cells and not to the cell membranes as found in malignancies with amplification of the c-erbB-2 oncogene. Two of the three overexpression cases were also positive by EGFR. No amplification of the c-erbB-2 gene was observed by FISH in the three tumours with immunohistochemical p185 overexpression or seven weakly positive/negative tumours. In conclusion, our results suggest that p185 overexpression is infrequent in astrocytomas, that it is of no important diagnostic or prognostic value and that c-erbB-2 oncogene amplification is not seen in the few cases in which there is overexpression. Images Figure 1 Figure 2 PMID:8605096

Prognostic significance of MYCN gene amplification and protein expression in primary brain tumors: Astrocytoma and meningioma.

PubMed

Estiar, Mehrdad Asghari; Javan, Firouzeh; Zekri, Ali; Mehrazin, Masoud; Mehdipour, Parvin

2017-07-04

Astrocytoma and meningioma are the most common primary brain tumors. MYCN as a member of MYC proto-oncogenes has recently appeared as an attractive therapeutic target. Functions of MYCN are critical for growth of nervous system and neural differentiation. We examined MYCN amplification and protein expression in astrocytoma and meningioma cases. In this study, we used real-time PCR, FISH assay and flowcytometry to analyze DNA amplification and protein expression of MYCN. Among 30 samples of brain tumor, 14 cases (46.6%) revealed MYCN amplification. High-protein expression of MYCN was also observed in 43.3% of patients. There was a significant correlation between MYCN gene amplification and protein expression (r= 0.523; p= 0.003), interestingly five case showed discrepancy between the gene amplification and protein expression. Although MYCN amplification fails to show correlation with poor prognosis (p= 0.305), protein high-expression of MYCN significantly reduce disease-free survival (p= 0.019). Our results challenge the concept of the neural specificity of MYCN by demonstrating contribution of MYCN in meningioma. Moreover, this study highlights the importance of research at both level of DNA and protein, to determine the biological functions and medical impacts of MYCN.

[Surgical treatment of diffuse adult orbital lymphangioma: two case studies].

PubMed

Berthout, A; Jacomet, P V; Putterman, M; Galatoire, O; Morax, S

2008-12-01

Orbital lymphangioma is a rare vascular malformation; it is a benign but severe anomaly because of its infiltrative, diffuse, and hemorrhagic nature, and its high morbidity rate. Surgical resection is a real challenge on account of the intricate architecture of the lesion. The authors report their surgical experience concerning two cases of diffuse orbital lymphangioma whose diagnosis was established in adulthood and whose surgical treatment was successful. Two patients presented with adult orbital lymphangioma. Progression was slow during the first decade and then was quickly followed by complications: major exorbitism, compressive optic neuropathy, and corneal exposure. Neuroimaging showed a diffuse and cystic orbital malformation. Surgical resection was performed as completely as possible, in one case with a Krönlein orbitotomy and in the other case only via a conjunctive route. An aspirate drain was put in the orbit for 48 h so as to prevent dead spaces forming after resection, an essential risk factor of hemorrhagic or cystic recurrence. Systemic corticotherapy was administered for the 5 days following surgery. The resection was total in one case and subtotal in the other. The surgical follow-up was uneventful with an excellent aesthetic result and an improvement in visual acuity. After 12 months, no tumoral or hemorrhagic recurrence was noted. The surgical treatment of orbital lymphangiomas is challenging because of their infiltrative nature. In diffuse forms, a complete resection is rarely possible because of the risk of sacrificing visual function. In the two cases reported herein, the resection of the extraconal portion was complete, but the intraconal portion was completely removed only in one case. Using the aspirate drain, negative pressure was maintained in the orbital cavity, preventing the formation of chocolate cysts induced by surgery. Although the clinical result was very satisfying, long-term follow-up is necessary to evaluate recurrence

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.

Diffusion and ADC-map images detect ongoing demyelination on subcortical white matter in an adult metachromatic leukodystrophy patient with autoimmune Hashimoto thyroiditis

PubMed Central

Miura, Akiko; Kumabe, Yuri; Kimura, En; Yamashita, Satoshi; Ueda, Akihiko; Hirano, Teruyuki; Uchino, Makoto

2010-01-01

Adult-onset metachromatic leukodystrophy (MLD) often shows schizophrenia- or encephalopathy-like symptoms at an early stage, such as behavioural abnormalities, cognitive impairment, mood disorders and hallucinations. The authors report the case of an adult woman with MLD who had been given antipsychotic medication for schizophrenia. In the differential diagnosis, screening of auto-antibodies was important for ruling out other encephalopathies as she had a euthyroid Hashimoto thyroiditis. Diagnosis was based the results of MRI, nerve conduction velocity, sensory evoked potential, motor evoked potential, lysosomal enzyme activity and gene analysis studies. Brain MRI showed diffuse demyelination spreading from the deep white matter to subcortical area as high signals at the edges of these lesions in diffusion and apparent diffusion coefficient-map images with the U-fibres conserved. The authors diagnosed adult-onset MLD coexisting with euthyroid autoimmune Hashimoto thyroiditis. PMID:22798296

Amide proton transfer imaging of adult diffuse gliomas: correlation with histopathological grades.

PubMed

Togao, Osamu; Yoshiura, Takashi; Keupp, Jochen; Hiwatashi, Akio; Yamashita, Koji; Kikuchi, Kazufumi; Suzuki, Yuriko; Suzuki, Satoshi O; Iwaki, Toru; Hata, Nobuhiro; Mizoguchi, Masahiro; Yoshimoto, Koji; Sagiyama, Koji; Takahashi, Masaya; Honda, Hiroshi

2014-03-01

Amide proton transfer (APT) imaging is a novel molecular MRI technique to detect endogenous mobile proteins and peptides through chemical exchange saturation transfer. We prospectively assessed the usefulness of APT imaging in predicting the histological grade of adult diffuse gliomas. Thirty-six consecutive patients with histopathologically proven diffuse glioma (48.1 ± 14.7 y old, 16 males and 20 females) were included in the study. APT MRI was conducted on a 3T clinical scanner and was obtained with 2 s saturation at 25 saturation frequency offsets ω = -6 to +6 ppm (step 0.5 ppm). δB0 maps were acquired separately for a point-by-point δB0 correction. APT signal intensity (SI) was defined as magnetization transfer asymmetry at 3.5 ppm: magnetization transfer ratio (MTR)asym = (S[-3.5 ppm] - S[+3.5 ppm])/S0. Regions of interest were carefully placed by 2 neuroradiologists in solid parts within brain tumors. The APT SI was compared with World Health Organization grade, Ki-67 labeling index (LI), and cell density. The mean APT SI values were 2.1 ± 0.4% in grade II gliomas (n = 8), 3.2 ± 0.9% in grade III gliomas (n = 10), and 4.1 ± 1.0% in grade IV gliomas (n = 18). Significant differences in APT intensity were observed between grades II and III (P < .05) and grades III and IV (P < .05), as well as between grades II and IV (P < .001). There were positive correlations between APT SI and Ki-67 LI (P = .01, R = 0.43) and between APT SI and cell density (P < .05, R = 0.38). The gliomas with microscopic necrosis showed higher APT SI than those without necrosis (P < .001). APT imaging can predict the histopathological grades of adult diffuse gliomas.

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. Copyright © 2015, American Association for the Advancement of Science.

Carfilzomib, Rituximab, and Combination Chemotherapy in Treating Patients With Diffuse Large B-Cell Lymphoma

ClinicalTrials.gov

2018-05-16

Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma

Strong FGFR3 staining is a marker for FGFR3 fusions in diffuse gliomas

PubMed Central

Annala, Matti; Lehtinen, Birgitta; Kesseli, Juha; Haapasalo, Joonas; Ruusuvuori, Pekka; Yli-Harja, Olli; Visakorpi, Tapio; Haapasalo, Hannu; Nykter, Matti; Zhang, Wei

2017-01-01

Abstract Background Inhibitors of fibroblast growth factor receptors (FGFRs) have recently arisen as a promising treatment option for patients with FGFR alterations. Gene fusions involving FGFR3 and transforming acidic coiled-coil protein 3 (TACC3) have been detected in diffuse gliomas and other malignancies, and fusion-positive cases have responded well to FGFR inhibition. As high FGFR3 expression has been detected in fusion-positive tumors, we sought to determine the clinical significance of FGFR3 protein expression level as well as its potential for indicating FGFR3 fusions. Methods We performed FGFR3 immunohistochemistry on tissue microarrays containing 676 grades II–IV astrocytomas and 116 grades II–III oligodendroglial tumor specimens. Fifty-one cases were further analyzed using targeted sequencing. Results Moderate to strong FGFR3 staining was detected in gliomas of all grades, was more common in females, and was associated with poor survival in diffuse astrocytomas. Targeted sequencing identified FGFR3-TACC3 fusions and an FGFR3-CAMK2A fusion in 10 of 15 strongly stained cases, whereas no fusions were found in 36 negatively to moderately stained cases. Fusion-positive cases were predominantly female and negative for IDH and EGFR/PDGFRA/MET alterations. These and moderately stained cases show lower MIB-1 proliferation index than negatively to weakly stained cases. Furthermore, stronger FGFR3 expression was commonly observed in malignant tissue regions of lower cellularity in fusion-negative cases. Importantly, subregional negative FGFR3 staining was also observed in a few fusion-positive cases. Conclusions Strong FGFR3 protein expression is indicative of FGFR3 fusions and may serve as a clinically applicable predictive marker for treatment regimens based on FGFR inhibitors. PMID:28379477

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

PubMed

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

2017-02-01

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

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

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.

Practical and adequate approach to modeling light propagation in an adult head with low-scattering regions by use of diffusion theory.

PubMed

Koyama, Tatsuya; Iwasaki, Atsushi; Ogoshi, Yosuke; Okada, Eiji

2005-04-10

A practical and adequate approach to modeling light propagation in an adult head with a low-scattering cerebrospinal fluid (CSF) region by use of diffusion theory was investigated. The diffusion approximation does not hold in a nonscattering or low-scattering regions. The hybrid radiosity-diffusion method was adopted to model the light propagation in the head with a nonscattering region. In the hybrid method the geometry of the nonscattering region is acquired as a priori information. In reality, low-level scattering occurs in the CSF region and may reduce the error caused by the diffusion approximation. The partial optical path length and the spatial sensitivity profile calculated by the finite-element method agree well with those calculated by the Monte Carlo method in the case in which the transport scattering coefficient of the CSF layer is greater than 0.3 mm(-1). Because it is feasible to assume that the transport scattering coefficient of a CSF layer is 0.3 mm(-1), it is practical to adopt diffusion theory to the modeling of light propagation in an adult head as an alternative to the hybrid method.

Practical and adequate approach to modeling light propagation in an adult head with low-scattering regions by use of diffusion theory

NASA Astrophysics Data System (ADS)

Koyama, Tatsuya; Iwasaki, Atsushi; Ogoshi, Yosuke; Okada, Eiji

2005-04-01

A practical and adequate approach to modeling light propagation in an adult head with a low-scattering cerebrospinal fluid (CSF) region by use of diffusion theory was investigated. The diffusion approximation does not hold in a nonscattering or low-scattering regions. The hybrid radiosity-diffusion method was adopted to model the light propagation in the head with a nonscattering region. In the hybrid method the geometry of the nonscattering region is acquired as a priori information. In reality, low-level scattering occurs in the CSF region and may reduce the error caused by the diffusion approximation. The partial optical path length and the spatial sensitivity profile calculated by the finite-element method agree well with those calculated by the Monte Carlo method in the case in which the transport scattering coefficient of the CSF layer is greater than 0.3 mm^-1. Because it is feasible to assume that the transport scattering coefficient of a CSF layer is 0.3 mm^-1, it is practical to adopt diffusion theory to the modeling of light propagation in an adult head as an alternative to the hybrid method.

Neurosurgical treatment of low-grade cerebellar astrocytoma in children and adolescents: a single consecutive institutional series of 100 patients.

PubMed

Due-Tønnessen, Bernt Johan; Lundar, Tryggve; Egge, Arild; Scheie, David

2013-03-01

The objective of this study was to delineate the long-term results of surgical treatment of pediatric low-grade cerebellar astrocytoma. One hundred consecutive children and adolescents (0-19 years old) who underwent primary tumor resection for a low-grade cerebellar astrocytoma during the years 1980-2011 were included in this retrospective study on surgical morbidity, mortality rate, academic achievement, and/or work participation. Gross motor function and activities of daily living were scored according to the Barthel Index. Of the 100 patients, 61 children were in the 1st decade, and 39 were 10-19 years old. The male/female ratio was 1.13:1 (53 males, 47 females). No patients were lost to follow-up. There were no deaths in this series and all 100 patients are currently alive. In 29 patients, the follow-up duration was less than 10 years, in 37 it was between 10 and 19 years, and in 34 it was between 20 and 31 years. The Barthel Index was 100 (normal) in 97 patients, 90 in 2 patients, and 40 in the last patient. A total of 113 tumor resections were performed. Two patients underwent further tumor resection due to MRI-confirmed residual tumor demonstrated on the immediate postoperative MR image (obtained the day after the initial procedure). Furthermore, 9 children underwent repeat tumor resection after MRI-confirmed progressive tumor recurrence up to 10 years after the initial operation. Two of these patients also underwent a third resection, without subsequent radiation therapy, and have experienced 8 and 12 years of tumor-free follow-up thereafter, respectively. A total of 15% of the patients required treatment for persistent hydrocephalus. Low-grade cerebellar astrocytoma is a surgical disease, in need of long-term follow-up, but with excellent long-term results. Nine percent of the children in this study underwent repeated surgery due to progressive tumor recurrence, and 15% were treated for persistent hydrocephalus.

Common pediatric cerebellar tumors: correlation between cell densities and apparent diffusion coefficient metrics.

PubMed

Koral, Korgün; Mathis, Derek; Gimi, Barjor; Gargan, Lynn; Weprin, Bradley; Bowers, Daniel C; Margraf, Linda

2013-08-01

To test whether there is correlation between cell densities and apparent diffusion coefficient (ADC) metrics of common pediatric cerebellar tumors. This study was reviewed for issues of patient safety and confidentiality and was approved by the Institutional Review Board of the University of Texas Southwestern Medical Center and was compliant with HIPAA. The need for informed consent was waived. Ninety-five patients who had preoperative magnetic resonance imaging and surgical pathologic findings available between January 2003 and June 2011 were included. There were 37 pilocytic astrocytomas, 34 medulloblastomas (23 classic, eight desmoplastic-nodular, two large cell, one anaplastic), 17 ependymomas (13 World Health Organization [WHO] grade II, four WHO grade III), and seven atypical teratoid rhabdoid tumors. ADCs of solid tumor components and normal cerebellum were measured. Tumor-to-normal brain ADC ratios (hereafter, ADC ratio) were calculated. The medulloblastomas and ependymomas were subcategorized according to the latest WHO classification, and tumor cellularity was calculated. Correlation was sought between cell densities and mean tumor ADCs, minimum tumor ADCs, and ADC ratio. When all tumors were considered together, negative correlation was found between cellularity and mean tumor ADCs (ρ = -0.737, P < .05) and minimum tumor ADCs (ρ = -0.736, P < .05) of common pediatric cerebellar tumors. There was no correlation between cellularity and ADC ratio. Negative correlation was found between cellularity and minimum tumor ADC in atypical teratoid rhabdoid tumors (ρ = -0.786, P < .05). In atypical teratoid rhabdoid tumors, no correlation was found between cellularity and mean tumor ADC and ADC ratio. There was no correlation between the ADC metrics and cellularity of the pilocytic astrocytomas, medulloblastomas, and ependymomas. Negative correlation was found between cellularity and ADC metrics of common pediatric cerebellar tumors. Although ADC metrics are

Molecular Classification of Low-Grade Diffuse Gliomas

PubMed Central

Kim, Young-Ho; Nobusawa, Sumihito; Mittelbronn, Michel; Paulus, Werner; Brokinkel, Benjamin; Keyvani, Kathy; Sure, Ulrich; Wrede, Karsten; Nakazato, Yoichi; Tanaka, Yuko; Vital, Anne; Mariani, Luigi; Stawski, Robert; Watanabe, Takuya; De Girolami, Umberto; Kleihues, Paul; Ohgaki, Hiroko

2010-01-01

The current World Health Organization classification recognizes three histological types of grade II low-grade diffuse glioma (diffuse astrocytoma, oligoastrocytoma, and oligodendroglioma). However, the diagnostic criteria, in particular for oligoastrocytoma, are highly subjective. The aim of our study was to establish genetic profiles for diffuse gliomas and to estimate their predictive impact. In this study, we screened 360 World Health Organization grade II gliomas for mutations in the IDH1, IDH2, and TP53 genes and for 1p/19q loss and correlated these with clinical outcome. Most tumors (86%) were characterized genetically by TP53 mutation plus IDH1/2 mutation (32%), 1p/19q loss plus IDH1/2 mutation (37%), or IDH1/2 mutation only (17%). TP53 mutations only or 1p/19q loss only was rare (2 and 3%, respectively). The median survival of patients with TP53 mutation ± IDH1/2 mutation was significantly shorter than that of patients with 1p/19q loss ± IDH1/2 mutation (51.8 months vs. 58.7 months, respectively; P = 0.0037). Multivariate analysis with adjustment for age and treatment confirmed these results (P = 0.0087) and also revealed that TP53 mutation is a significant prognostic marker for shorter survival (P = 0.0005) and 1p/19q loss for longer survival (P = 0.0002), while IDH1/2 mutations are not prognostic (P = 0.8737). The molecular classification on the basis of IDH1/2 mutation, TP53 mutation, and 1p/19q loss has power similar to histological classification and avoids the ambiguity inherent to the diagnosis of oligoastrocytoma. PMID:21075857

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

ClinicalTrials.gov

2018-04-12

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

Evaluation of guggulipid and nimesulide on production of inflammatory mediators and GFAP expression in LPS stimulated rat astrocytoma, cell line (C6).

PubMed

Niranjan, Rituraj; Kamat, Pradeep Kumar; Nath, Chandishwar; Shukla, Rakesh

2010-02-17

The present study was designed to investigate effect of guggulipid, a drug developed by CDRI and nimesulide on LPS stimulated neuroinflammatory changes in rat astrocytoma cell line (C6). Rat astrocytoma cells (C6) were stimulated with LPS (10 microg/ml) alone and in combinations with different concentrations of guggulipid or nimesulide for 24h of incubation. Nitrite release in culture supernatant, ROS in cells, expressions of COX-2, GFAP and TNF-alpha in cell lysate were estimated. LPS (10 microg/ml) stimulated C6 cells to release nitrite, ROS generation, up regulated COX-2 and GFAP expressions at protein level and TNF-alpha at mRNA level. Both guggulipid and nimesulide significantly attenuated nitrite release, ROS generation and also down regulated expressions of COX-2, GFAP and TNF-alpha. Guggulipid and nimesulide per se did not have any significant effect on C6 cells. Results demonstrate the anti-inflammatory effect of guggulipid comparable to nimesulide which suggest potential use of guggulipid in neuroinflammation associated conditions in CNS disorders. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Prognostic Relevance of Histomolecular Classification of Diffuse Adult High-Grade Gliomas with Necrosis.

PubMed

Figarella-Branger, Dominique; Mokhtari, Karima; Colin, Carole; Uro-Coste, Emmanuelle; Jouvet, Anne; Dehais, Caroline; Carpentier, Catherine; Villa, Chiara; Maurage, Claude-Alain; Eimer, Sandrine; Polivka, Marc; Vignaud, Jean-Michel; Laquerriere, Annie; Sevestre, Henri; Lechapt-Zalcman, Emmanuelle; Quintin-Roué, Isabelle; Aubriot-Lorton, Marie-Hélène; Diebold, Marie-Danièle; Viennet, Gabriel; Adam, Clovis; Loussouarn, Delphine; Michalak, Sophie; Rigau, Valérie; Heitzmann, Anne; Vandenbos, Fanny; Forest, Fabien; Chiforeanu, Danchristian; Tortel, Marie-Claire; Labrousse, François; Chenard, Marie-Pierre; Nguyen, Anh Tuan; Varlet, Pascale; Kemeny, Jean Louis; Levillain, Pierre-Marie; Cazals-Hatem, Dominique; Richard, Pomone; Delattre, Jean-Yves

2015-07-01

Diffuse adult high-grade gliomas (HGGs) with necrosis encompass anaplastic oligodendrogliomas (AOs) with necrosis (grade III), glioblastomas (GBM, grade IV) and glioblastomas with an oligodendroglial component (GBMO, grade IV). Here, we aimed to search for prognostic relevance of histological classification and molecular alterations of these tumors. About 210 patients were included (63 AO, 56 GBM and 91 GBMO). GBMO group was split into "anaplastic oligoastrocytoma (AOA) with necrosis grade IV/GBMO," restricted to tumors showing intermingled astrocytic and oligodendroglial component, and "GBM/GBMO" based on tumors presenting oligodendroglial foci and features of GBM. Genomic arrays, IDH1 R132H expression analyses and IDH direct sequencing were performed. 1p/19q co-deletion characterized AO, whereas no IDH1 R132H expression and intact 1p/19q characterized both GBM and GBM/GBMO. AOA with necrosis/GBMO mainly demonstrated IDH1 R132H expression and intact 1p/19q. Other IDH1 or IDH2 mutations were extremely rare. Both histological and molecular classifications were predictive of progression free survival (PFS) and overall survival (OS) (P < 10(-4) ). Diffuse adult HGGs with necrosis can be split into three histomolecular groups of prognostic relevance: 1p/19q co-deleted AO, IDH1 R132H-GBM and 1p/19q intact IDH1 R132H+ gliomas that might be classified as IDH1 R132H+ GBM. Because of histomolecular heterogeneity, we suggest to remove the name GBMO. © 2014 International Society of Neuropathology.

Vorinostat and Radiation Therapy Followed by Maintenance Therapy With Vorinostat in Treating Younger Patients With Newly Diagnosed Diffuse Intrinsic Pontine Glioma

ClinicalTrials.gov

2018-06-19

Anaplastic Astrocytoma; Anaplastic Oligoastrocytoma; Brain Stem Glioma; Childhood Glioblastoma; Giant Cell Glioblastoma; Gliosarcoma; Untreated Childhood Anaplastic Astrocytoma; Untreated Childhood Anaplastic Oligoastrocytoma; Untreated Childhood Brain Stem Glioma; Untreated Childhood Giant Cell Glioblastoma; Untreated Childhood Gliosarcoma

Finding of IDH1 R132H mutation in histologically non-neoplastic glial tissue changes surgical strategies, a case report.

PubMed

Søndergaard, Christian Baastrup; Scheie, David; Sehested, Astrid Marie; Skjøth-Rasmussen, Jane

2017-07-01

In 2016, the WHO classification of diffuse astrocytoma began to include isocitrate dehydrogenase (IDH) mutation in addition to histology. We here demonstrate a case where a 14-year-old boy presented with a parietal tumor with no histological evidence of neoplasia but with an IDH1 mutation. Due to the IDH1 R132H mutation, the patient was diagnosed with diffuse astrocytoma WHO grade II and underwent successful gross total resection of this near-eloquently located tumor. This case exemplifies how inclusion of immunohistochemistry in tumor classification alters surgical strategy and might improve accuracy and time to diagnosis.

Rituximab and Combination Chemotherapy in Treating Patients With Previously Untreated High- or High-Intermediate-Risk Diffuse Large B-Cell Lymphoma

ClinicalTrials.gov

2016-03-01

Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma

Resection of a Pediatric Thalamic Juvenile Pilocytic Astrocytoma with Whole Brain Tractography

PubMed Central

Weiner, Howard L

2017-01-01

The resection of deep-seated brain tumors has been associated with morbidity due to injury to critical neural structures during the approach. Recent technological advancements in navigation and stereotaxy, surgical planning, brain tractography and minimal-access brain ports present the opportunity to overcome such limitations. Here, we present the case of a pediatric patient with a left thalamic/midbrain juvenile pilocytic astrocytoma (JPA). The tumor displaced the corticospinal fibers posteriorly and resulted in hemiparesis. Using whole brain tractography to plan a corridor for the approach, neuronavigation, a tubular retractor and an exoscope for visualization, we obtained gross total resection of the tumor, while minimizing injury to white matter bundles, including the corticospinal fibers. We propose that surgical planning with whole brain tractography is essential for reducing morbidity while accessing deep-lying brain lesions via retractor tubes, by means of sparing critical fiber tracts. PMID:29234572

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

PubMed

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.

Diffusion tensor imaging (DTI) findings in adult civilian, military, and sport-related mild traumatic brain injury (mTBI): a systematic critical review.

PubMed

Asken, Breton Michael; DeKosky, Steven T; Clugston, James R; Jaffee, Michael S; Bauer, Russell M

2018-04-01

This review seeks to summarize diffusion tensor imaging (DTI) studies that have evaluated structural changes attributed to the mechanisms of mild traumatic brain injury (mTBI) in adult civilian, military, and athlete populations. Articles from 2002 to 2016 were retrieved from PubMed/MEDLINE, EBSCOhost, and Google Scholar, using a Boolean search string containing the following terms: "diffusion tensor imaging", "diffusion imaging", "DTI", "white matter", "concussion", "mild traumatic brain injury", "mTBI", "traumatic brain injury", and "TBI". We added studies not identified by this method that were found via manually-searched reference lists. We identified 86 eligible studies from English-language journals using, adult, human samples. Studies were evaluated based on duration between injury and DTI assessment, categorized as acute, subacute/chronic, remote mTBI, and repetitive brain trauma considerations. Since changes in brain structure after mTBI can also be affected by other co-occurring medical and demographic factors, we also briefly review DTI studies that have addressed socioeconomic status factors (SES), major depressive disorder (MDD), and attention-deficit hyperactivity disorder (ADHD). The review describes population-specific risks and the complications of clinical versus pathophysiological outcomes of mTBI. We had anticipated that the distinct population groups (civilian, military, and athlete) would require separate consideration, and various aspects of the study characteristics supported this. In general, study results suggested widespread but inconsistent differences in white matter diffusion metrics (primarily fractional anisotropy [FA], mean diffusivity [MD], radial diffusivity [RD], and axial diffusivity [AD]) following mTBI/concussion. Inspection of study designs and results revealed potential explanations for discrepant DTI findings, such as control group variability, analytic techniques, the manner in which regional differences were reported, and

relationship between diffusion tensor imaging findings and cognitive outcomes following adult traumatic brain injury: A meta-analysis.

PubMed

Wallace, E J; Mathias, J L; Ward, L

2018-05-24

Cognitive impairments are common following a traumatic brain injury (TBI) and frequently result from white matter (WM) damage. This damage can be quantified using diffusion tensor imaging (DTI), which measures the directionality (fractional anisotropy: FA) and amount (mean diffusivity/apparent diffusion coefficient: MD/ADC) of water diffusion in WM, with high FA and low MD/ADC thought to indicate greater WM integrity. However, the relationship between DTI and cognitive outcomes is currently unclear. The data from 20 studies that examined the relationship between WM integrity (measured using DTI) and cognition (categorised into seven domains) following mild-severe adult TBI were meta-analysed. Overall, high FA and low MD/ADC in most brain regions was associated with better cognitive performance, with memory and attention most strongly related to DTI findings. Specifically, memory and/or attention were very strongly related to DTI findings in the corpus callosum, fornix, internal capsule, arcuate and uncinate fasciculi. However, most findings were based on single studies and therefore await replication. Larger-scale, longitudinal studies are now needed to determine the predictive utility of DTI. Copyright © 2018. Published by Elsevier Ltd.

A huge intraventricular congenital anaplastic astrocytoma: case report with histopathological and genetic consideration.

PubMed

Yamashita, Shinji; Ryu, Shinitsu; Miyata, Shiro; Uchinokura, Syunrou; Yokogami, Kiyotaka; Uehara, Hisao; Moriguchi, Sayaka; Iwakiri, Takashi; Marutsuka, Kousuke; Ikenoue, Makoto; Sawa, Daisuke; Yamada, Naoshi; Kodama, Yuki; Takeshima, Hideo

2012-04-01

Congenital malignant gliomas are rare brain tumors about which few reports have been published. We present the clinical course and genetic alterations in an infant with a congenital malignant glioma detected incidentally by ultrasonography at 36 weeks. The tumor occupied the right temporoparietal region, extended to the posterior fossa, and significantly compressed surrounding structures. The female infant was entirely normal without macrocrania, tense fontanel, or sucking difficulties. The tumor was subtotally resected by two-stage surgery; pathological diagnosis was anaplastic astrocytoma. Immunohistochemical staining was positive for p53 and negative for epidermal growth factor receptor. There was no O(6)-methylguanine-DNA methyltransferase (MGMT) gene promoter methylation, no 1p/19q loss of heterozygosity, and no isocitrate dehydrogenase 1 (IDH1) mutation. She underwent postoperative chemotherapy and is alive and well 12 months after surgery.

Diffusion abnormalities in adolescents and young adults with a history of heavy cannabis use.

PubMed

Ashtari, Manzar; Cervellione, Kelly; Cottone, John; Ardekani, Babak A; Sevy, Serge; Kumra, Sanjiv

2009-01-01

There is growing evidence that adolescence is a key period for neuronal maturation. Despite the high prevalence of marijuana use among adolescents and young adults in the United States and internationally, very little is known about its impact on the developing brain. Based on neuroimaging literature on normal brain developmental during adolescence, we hypothesized that individuals with heavy cannabis use (HCU) would have brain structure abnormalities in similar brain regions that undergo development during late adolescence, particularly the fronto-temporal connection. Fourteen young adult males in residential treatment for cannabis dependence and 14 age-matched healthy male control subjects were recruited. Patients had a history of HCU throughout adolescence; 5 had concurrent alcohol abuse. Subjects underwent structural and diffusion tensor magnetic resonance imaging. White matter integrity was compared between subject groups using voxelwise and fiber tractography analysis. Voxelwise and tractography analyses revealed that adolescents with HCU had reduced fractional anisotropy, increased radial diffusivity, and increased trace in the homologous areas known to be involved in ongoing development during late adolescence, particularly in the fronto-temporal connection via arcuate fasciculus. Our results support the hypothesis that heavy cannabis use during adolescence may affect the trajectory of normal brain maturation. Due to concurrent alcohol consumption in five HCU subjects, conclusions from this study should be considered preliminary, as the DTI findings reported here may be reflective of the combination of alcohol and marijuana use. Further research in larger samples, longitudinal in nature, and controlling for alcohol consumption is needed to better understand the pathophysiology of the effect of cannabis on the developing brain.

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

2017-11-07

Adult Anaplastic Astrocytoma; Recurrent Grade III Glioma; Recurrent Grade IV Glioma; Adult Anaplastic Oligodendroglioma; Adult Brain Tumor; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Recurrent Adult Brain Tumor; Adult Anaplastic Oligoastrocytoma; Recurrent High Grade Glioma

Participation and Diffusion Effects of a Peer-Intervention for HIV Prevention among Adults in Rural Malawi

PubMed Central

Crittenden, Kathleen S.; Kaponda, Chrissie P. N.; Jere, Diana L.; McCreary, Linda L.; Norr, Kathleen F.

2015-01-01

This paper examines whether a peer group intervention that reduced self-reported risky behaviors for rural adults in Malawi also had impacts on non-participants in the same communities. We randomly assigned two districts to the intervention and control conditions, and conducted surveys at baseline and 18 months post-intervention using unmatched independent random samples of intervention and control communities in 2003-2006. The six-session peer group intervention was offered to same-gender groups by trained volunteers. In this analysis, we divided the post-intervention sample into three exposure groups: 243 participants and 170 non-participants from the intervention district (total n=415) and 413 control individuals. Controlling for demographics and participation, there were significant favorable diffusion effects on five partially overlapping behavioral outcomes: partner communication, ever used condoms, unprotected sex, recent HIV test, and a community HIV prevention index. Non-participants in the intervention district had more favorable outcomes on these behaviors than survey respondents in the control district. One behavioral outcome, community HIV prevention, showed both participation and diffusion effects. Participating in the intervention had a significant effect on six psychosocial outcomes: HIV knowledge (two measures), hope, condom attitudes, and self-efficacy for community HIV prevention and for safer sex; there were no diffusion effects. This pattern of results suggests that the behavioral changes promoted in the intervention spread to others in the same community, most likely through direct contact between participants and non-participants. These findings support the idea that diffusion of HIV-related behavior changes can occur for peer group interventions in communities, adding to the body of research supporting diffusion of innovations theory as a robust approach to accelerating change. If diffusion occurs, peer group intervention may be more cost

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

Human neuroblastoma growth inhibitory factor (h-NGIF), derived from human astrocytoma conditioned medium, has neurotrophic properties.

PubMed

Eksioglu, Y Z; Iida, J; Asai, K; Ueki, T; Nakanishi, K; Isobe, I; Yamagata, K; Kato, T

1994-05-02

Investigations on the general characteristics of human astrocytoma cell line NAC-1 revealed neuroblastoma growth inhibitory activity in conditioned medium. Neuroblastoma growth inhibitory factor (NGIF) was partially purified by Econo Q, Econo CM, and Superose 12 column chromatography. The protein is weakly basic with an estimated M(r) of 120,000, possibly having an M(r) 60,000 dimeric structure. NGIF inhibits the growth of human neuroblastoma cell lines but has no effect on morphology nor does it produce any change in the growth of human glioblastoma cell lines. Interestingly, NGIF appears to promote survival and neurite outgrowth of embryonal rat cortical neurons. These neurotrophic properties suggest a role for NGIF in the development of the nervous system.

Brain Perfusion and Diffusion Abnormalities in Children Treated for Posterior Fossa Brain Tumors.

PubMed

Li, Matthew D; Forkert, Nils D; Kundu, Palak; Ambler, Cheryl; Lober, Robert M; Burns, Terry C; Barnes, Patrick D; Gibbs, Iris C; Grant, Gerald A; Fisher, Paul G; Cheshier, Samuel H; Campen, Cynthia J; Monje, Michelle; Yeom, Kristen W

2017-06-01

To compare cerebral perfusion and diffusion in survivors of childhood posterior fossa brain tumor with neurologically normal controls and correlate differences with cognitive dysfunction. We analyzed retrospectively arterial spin-labeled cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) in 21 patients with medulloblastoma (MB), 18 patients with pilocytic astrocytoma (PA), and 64 neurologically normal children. We generated ANCOVA models to evaluate treatment effects on the cerebral cortex, thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala, nucleus accumbens, and cerebral white matter at time points an average of 5.7 years after original diagnosis. A retrospective review of patient charts identified 12 patients with neurocognitive data and in whom the relationship between IQ and magnetic resonance imaging variables was assessed for each brain structure. Patients with MB (all treated with surgery, chemotherapy, and radiation) had significantly lower global CBF relative to controls (10%-23% lower, varying by anatomic region, all adjusted P?diffusion abnormalities of the mesial temporal lobe structures. Despite significant perfusion abnormalities in patients with MB, diffusion, but not perfusion, correlated with cognitive outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

Diffusion tensor imaging reveals adolescent binge ethanol-induced brain structural integrity alterations in adult rats that correlate with behavioral dysfunction.

PubMed

Vetreno, Ryan P; Yaxley, Richard; Paniagua, Beatriz; Crews, Fulton T

2016-07-01

Adolescence is characterized by considerable brain maturation that coincides with the development of adult behavior. Binge drinking is common during adolescence and can have deleterious effects on brain maturation because of the heightened neuroplasticity of the adolescent brain. Using an animal model of adolescent intermittent ethanol [AIE; 5.0 g/kg, intragastric, 20 percent EtOH w/v; 2 days on/2 days off from postnatal day (P)25 to P55], we assessed the adult brain structural volumes and integrity on P80 and P220 using diffusion tensor imaging (DTI). While we did not observe a long-term effect of AIE on structural volumes, AIE did reduce axial diffusivity (AD) in the cerebellum, hippocampus and neocortex. Radial diffusivity (RD) was reduced in the hippocampus and neocortex of AIE-treated animals. Prior AIE treatment did not affect fractional anisotropy (FA), but did lead to long-term reductions of mean diffusivity (MD) in both the cerebellum and corpus callosum. AIE resulted in increased anxiety-like behavior and diminished object recognition memory, the latter of which was positively correlated with DTI measures. Across aging, whole brain volumes increased, as did volumes of the corpus callosum and neocortex. This was accompanied by age-associated AD reductions in the cerebellum and neocortex as well as RD and MD reductions in the cerebellum. Further, we found that FA increased in both the cerebellum and corpus callosum as rats aged from P80 to P220. Thus, both age and AIE treatment caused long-term changes to brain structural integrity that could contribute to cognitive dysfunction. © 2015 Society for the Study of Addiction.

Oblimersen Sodium and Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage I, Stage II, Stage III, or Stage IV Diffuse Large B-Cell Lymphoma

ClinicalTrials.gov

2012-10-11

Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma

Tectal gliomas: assessment of malignant progression, clinical management, and quality of life in a supposedly benign neoplasm.

PubMed

Mohme, Malte; Fritzsche, Friederike S; Mende, Klaus C; Matschke, Jakob; Löbel, Ulrike; Kammler, Gertrud; Westphal, Manfred; Emami, Pedram; Martens, Tobias

2018-06-01

OBJECTIVE Tectal gliomas constitute a rare and inhomogeneous group of lesions with an uncertain clinical course. Because these supposedly benign tumors are frequently followed up by observation over many years, the authors undertook this analysis of their own case series in an effort to demonstrate that the clinical course is highly variable and that there is a potential for a progressive biology. METHODS Clinical data analysis of 23 cases of tectal glioma (involving 9 children and 14 adults) was performed retrospectively. Radiographic data were analyzed longitudinally and MR images were evaluated for tumor volume, contrast enhancement, and growth progression. Quality of life was assessed using the EORTC BN20 and C30 questionnaires during follow-up in a subgroup of patients. RESULTS The patients' mean age at diagnosis was 29.2 years. The main presenting symptom at diagnosis was hydrocephalus (80%). Six patients were treated by primary tumor resection (26.1%), 3 patients underwent biopsy followed by resection (13.1%), and 3 patients underwent biopsy only (13.1%). For additional treatment of hydrocephalus, 14 patients (60.9%) received shunts and/or endoscopic third ventriculostomy. Radiographic tumor progression was observed in 47.9% of the 23 cases. The mean time between diagnosis and growth progression was 51.5 months, and the mean time to contrast enhancement was 69.7 months. Histopathological analysis was obtained in 12 cases (52.2%), resulting in 5 cases of high-grade glioma (3 cases of glioblastoma multiforme [GBM], grade IV, and 2 of anaplastic astrocytoma, grade III), 5 cases of pilocytic astrocytoma, 1 diffuse astrocytoma, and 1 ganglioglioma. Malignant progression was observed in 2 cases, with 1 case progressing from a diffuse astrocytoma (grade II) to a GBM (grade IV) within a period of 13 years. Quality-of-life measurements demonstrated distinct functional deficits compared to a healthy sample as well as glioma control cohorts. CONCLUSIONS Analysis of

Vorinostat, Rituximab, and Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage II, Stage III, or Stage IV Diffuse Large B-Cell Lymphoma

ClinicalTrials.gov

2017-09-12

Stage II Contiguous Adult Diffuse Large Cell Lymphoma; Stage II Non-Contiguous Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma

Glioneuronal tumor with neuropil-like islands of the spinal cord with diffuse leptomeningeal neuraxis dissemination.

PubMed

Ruppert, Bree; Welsh, Cynthia T; Hannah, Jessica; Giglio, Pierre; Rumboldt, Zoran; Johnson, Ian; Fortney, John; Jenrette, Joseph M; Patel, Sunil; Scheithauer, Bernd W

2011-09-01

A 54-year-old Caucasian female presented with a 1 year history of intermittent numbness of the left leg progressing to bilateral, lower extremity sensory loss that advanced to include impaired vibration and proprioception. The subsequent thoracic spine magnetic resonance imaging (MRI) scan revealed a heterogeneous, avidly enhancing, centrally situated spinal cord mass involving T7 through T10 in association with thick linear enhancement of the anterior and posterior cord surfaces extending both superiorly and inferiorly. Both the cervical and lumbar spine MRI demonstrated diffuse leptomeningeal disease as well. A brain MRI revealed focal leptomeningeal enhancement in the left and right sylvian fissures, the suprasellar cistern, and the posterior fossa; a pattern consistent with metastatic disease. The patient underwent a T6-T10 laminectomy for tumor biopsy and debulking. Histology revealed a WHO grade III glioneuronal tumor with rosetted neuropil-like islands. Synaptophysin and neurofilament (NF) positive staining was noted within the neural appearing component, whereas, glial fibrillary acidic protein (GFAP) immunopositivity was evident in the fibrillary astrocytoma component of the tumor. The Ki-67 labeling index was 7%. This tumor pattern, now included in the 2007 World Health Organization (WHO) classification of central nervous system tumours as a pattern variation of anaplastic astrocytoma (Kleihues et al. In: Louis et al. (eds) WHO classification of tumours of the central nervous system, 2007), was first described in a four-case series by Teo et al. in 1999. The majority of subsequently reported cases described them as primary tumors of the cerebrum. Herein, we report a unique example of a spinal glioneuronal tumor with neuropil-like islands with associated leptomeningeal dissemination involving the entire craniospinal axis.

Imaging findings of anaplastic astrocytoma in a child with maple syrup urine disease: a case report.

PubMed

Aw-Zoretic, Jessie; Wadhwani, Nitin R; Lulla, Rishi R; Rishi, Lulla R; Ryan, Maura E

2015-09-01

Maple syrup urine disease (MSUD) is an inborn error of branched-chain amino acid metabolism, which usually presents in childhood with encephalopathy due to cerebral edema and dysmyelination. Even with treatment, metabolic stressors may precipitate later episodes of acute decompensation. Changes related to cerebral and white matter edema have been described by magnetic resonance imaging (MRI), and imaging can aid in both initial diagnosis and evaluation of decompensation. To date, there are no published known reports of cancer in patients with MSUD. Here, we present the first case report of an anaplastic astrocytoma in a teenager with MSUD, with a discussion of imaging findings and the use of magnetic resonance spectroscopy (MRS) to help distinguish between tumor and metabolic changes.

Participation and diffusion effects of a peer-intervention for HIV prevention among adults in rural Malawi.

PubMed

Crittenden, Kathleen S; Kaponda, Chrissie P N; Jere, Diana L; McCreary, Linda L; Norr, Kathleen F

2015-05-01

This paper examines whether a peer group intervention that reduced self-reported risky behaviors for rural adults in Malawi also had impacts on non-participants in the same communities. We randomly assigned two districts to the intervention and control conditions, and conducted surveys at baseline and 18 months post-intervention using unmatched independent random samples of intervention and control communities in 2003-2006. The six-session peer group intervention was offered to same-gender groups by trained volunteers. In this analysis, we divided the post-intervention sample into three exposure groups: 243 participants and 170 non-participants from the intervention district (total n = 415) and 413 control individuals. Controlling for demographics and participation, there were significant favorable diffusion effects on five partially overlapping behavioral outcomes: partner communication, ever used condoms, unprotected sex, recent HIV test, and a community HIV prevention index. Non-participants in the intervention district had more favorable outcomes on these behaviors than survey respondents in the control district. One behavioral outcome, community HIV prevention, showed both participation and diffusion effects. Participating in the intervention had a significant effect on six psychosocial outcomes: HIV knowledge (two measures), hope, condom attitudes, and self-efficacy for community HIV prevention and for safer sex; there were no diffusion effects. This pattern of results suggests that the behavioral changes promoted in the intervention spread to others in the same community, most likely through direct contact between participants and non-participants. These findings support the idea that diffusion of HIV-related behavior changes can occur for peer group interventions in communities, adding to the body of research supporting diffusion of innovations theory as a robust approach to accelerating change. If diffusion occurs, peer group intervention may be more

S0349 Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone With or Without Oblimersen in Treating Patients With Advanced Diffuse Large B-Cell Non-Hodgkin's Lymphoma

ClinicalTrials.gov

2013-01-04

Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma

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.

Brain tumour cells interconnect to a functional and resistant network.

PubMed

Osswald, Matthias; Jung, Erik; Sahm, Felix; Solecki, Gergely; Venkataramani, Varun; Blaes, Jonas; Weil, Sophie; Horstmann, Heinz; Wiestler, Benedikt; Syed, Mustafa; Huang, Lulu; Ratliff, Miriam; Karimian Jazi, Kianush; Kurz, Felix T; Schmenger, Torsten; Lemke, Dieter; Gömmel, Miriam; Pauli, Martin; Liao, Yunxiang; Häring, Peter; Pusch, Stefan; Herl, Verena; Steinhäuser, Christian; Krunic, Damir; Jarahian, Mostafa; Miletic, Hrvoje; Berghoff, Anna S; Griesbeck, Oliver; Kalamakis, Georgios; Garaschuk, Olga; Preusser, Matthias; Weiss, Samuel; Liu, Haikun; Heiland, Sabine; Platten, Michael; Huber, Peter E; Kuner, Thomas; von Deimling, Andreas; Wick, Wolfgang; Winkler, Frank

2015-12-03

Astrocytic brain tumours, including glioblastomas, are incurable neoplasms characterized by diffusely infiltrative growth. Here we show that many tumour cells in astrocytomas extend ultra-long membrane protrusions, and use these distinct tumour microtubes as routes for brain invasion, proliferation, and to interconnect over long distances. The resulting network allows multicellular communication through microtube-associated gap junctions. When damage to the network occurred, tumour microtubes were used for repair. Moreover, the microtube-connected astrocytoma cells, but not those remaining unconnected throughout tumour progression, were protected from cell death inflicted by radiotherapy. The neuronal growth-associated protein 43 was important for microtube formation and function, and drove microtube-dependent tumour cell invasion, proliferation, interconnection, and radioresistance. Oligodendroglial brain tumours were deficient in this mechanism. In summary, astrocytomas can develop functional multicellular network structures. Disconnection of astrocytoma cells by targeting their tumour microtubes emerges as a new principle to reduce the treatment resistance of this disease.

[Guidelines for adult diffuse gliomas WHO grade II, III and IV: pathology and biology. Société franc¸aise de neuropathologie . Réseau de neuro-oncologie pathologique].

PubMed

Figarella-Branger, Dominique; Labrousse, François; Mohktari, Karima

2012-10-01

Pathological diagnosis plays a major role in the therapeutic management of adult diffuse gliomas. It is based on the histopathological analysis of a representative specimen. Therefore pathologists might be aware of the neuroradiological features of the lesions. Pathologists play a major role in the management of biological resources. Pathologists should classify adult gliomas according to WHO 2007 classification (histological subtype and grade). In addition, in order to provide the histomolecular classification of adult gliomas, search for molecular markers of diagnostic, prognostic or predictive of therapeutic responses must be performed by appropriate and validated immunohistochemical and molecular techniques. In all diffuse gliomas, whatever their grade, search for IDH1 R132H and P53 expression is required. Search for IDH1 minor mutations and IDH2 mutations is required in grade II and III IDH1 R132H negative gliomas whereas 1p19q codeletion should be searched for in grade II and III gliomas with an oligodendroglial component. Search for EGFR amplification and MGMT promoter methylation is recommended. It is strongly recommended to fill the standardized form for pathology and molecular features (validated by the French Society of Neuropathology) in all adult diffuse gliomas. Copyright © 2012. Published by Elsevier Masson SAS.

Anaplasic astrocytoma with exophytic growth in Sylvian fissure in a pediatric patient: a case report.

PubMed

Guerra-Mora, José Raúl; Bravo-Ángel, Ulises; Hernández-Reséndiz, Rodrigo Efraín; Vicuña-González, Rosa María; Frías-Guillén, Jessica; Bercholc-Urinowsky, Irina Jeanette; Bravo-Reyna, Carlos Cesar; García-González, Ulises

2018-04-01

Gliomas are the most frequent supratentorial intracranial tumors in the pediatric population. Usually, they are intra-axial lesions with a characteristic image pattern, however, there are few reported cases of gliomas with exophytic growth. There are no previous reports in the literature of gliomas with exophytic growth in the Sylvian fissure. Fourteen year-old female patient who started with seizures. In imaging studies, a neoplasic mass with an exophytic portion in the left Sylvian fissure was found. Macroscopically, total resection was performed, definitive diagnosis was anaplastic astrocytoma. She presented recurrence and is currently receiving adjuvant treatment. Supratentorial gliomas with exophytic growth are extremely rare. We report the first case in the pediatric population, and we consider it is important to know its imaging and macroscopic characteristics for its initial management and to take it into account as a differential diagnosis of exophytic lesions.

Everolimus Alleviates Obstructive Hydrocephalus due to Subependymal Giant Cell Astrocytomas.

PubMed

Moavero, Romina; Carai, Andrea; Mastronuzzi, Angela; Marciano, Sara; Graziola, Federica; Vigevano, Federico; Curatolo, Paolo

2017-03-01

Subependymal giant cell astrocytomas (SEGAs) are low-grade tumors affecting up to 20% of patients with tuberous sclerosis complex (TSC). Early neurosurgical resection has been the only standard treatment until few years ago when a better understanding of the molecular pathogenesis of TSC led to the use of mammalian target of rapamycin (mTOR) inhibitors. Surgical resection of SEGAs is still considered as the first line treatment in individuals with symptomatic hydrocephalus and intratumoral hemorrhage. We describe four patients with symptomatic or asymptomatic hydrocephalus who were successfully treated with the mTOR inhibitor everolimus. We collected the clinical data of four consecutive patients presenting with symptomatic or asymptomatic hydrocephalus due to a growth of subependymal giant cell atrocytomas and who could not undergo surgery for different reasons. All patients experienced a clinically significant response to everolimus and an early shrinkage of the SEGA with improvement in ventricular dilatation. Everolimus was well tolerated by all individuals. Our clinical series demonstrate a possible expanding indication for mTOR inhibition in TSC, which can be considered in patients with asymptomatic hydrocephalus or even when the symptoms already appeared. It offers a significant therapeutic alternative to individuals that once would have undergone immediate surgery. Everolimus might also allow postponement of a neurosurgical resection, making it elective with an overall lower risk. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

Pneumopathie interstitielle diffuse révélant la leucémie-lymphome à cellules T de l’adulte HTLV1+

PubMed Central

Bouanani, Nouama; Lamchahab, Mouna

2016-01-01

La leucémie/lymphome à cellules T de l'adulte est une prolifération tumorale de cellules lymphoïdes T matures activées, dont l'agent étiologique est le rétrovirus humain T cell-leukemia virus type 1, ce virus entraine rarement des désordres inflammatoires bronchioloalveolaires. Nous rapportons l'observation d'un patient hospitalisé pour une pneumopathie interstitielle diffuse et dont le bilan étiologique a révélé une leucémie lymphome à cellules T de l'adulte HTLV1+. PMID:28292112

Roel Verhaak, Ph.D., Presents the Somatic Genomic Landscape of Glioblastoma - TCGA

Cancer.gov

Diffuse lower grade gliomas (LGGs) are infiltrative neoplasms of the central nervous system that include astrocytoma, oligodendroglioma and oligo-astrocytoma histologies of grades II and III. Roel G.W. Verhaak, Ph.D., presents a comprehensive analysis of 293 LGGs using multiple advanced genomic, transcriptomic and proteomic platforms from The Cancer Genome Atlas to provide a deeper understanding of the molecular features of this group of neoplasms, to classify them in a clinically-relevant manner, and to provide a public resource that identifies potential targets for emerging therapies.

Anaplasic astrocytoma with exophytic growth in Sylvian fissure in a pediatric patient: a case report

PubMed Central

Bravo-Ángel, Ulises; Hernández-Reséndiz, Rodrigo Efraín; Vicuña-González, Rosa María; Frías-Guillén, Jessica; Bercholc-Urinowsky, Irina Jeanette; Bravo-Reyna, Carlos Cesar; García-González, Ulises

2018-01-01

Abstract Gliomas are the most frequent supratentorial intracranial tumors in the pediatric population. Usually, they are intra-axial lesions with a characteristic image pattern, however, there are few reported cases of gliomas with exophytic growth. There are no previous reports in the literature of gliomas with exophytic growth in the Sylvian fissure. Fourteen year-old female patient who started with seizures. In imaging studies, a neoplasic mass with an exophytic portion in the left Sylvian fissure was found. Macroscopically, total resection was performed, definitive diagnosis was anaplastic astrocytoma. She presented recurrence and is currently receiving adjuvant treatment. Supratentorial gliomas with exophytic growth are extremely rare. We report the first case in the pediatric population, and we consider it is important to know its imaging and macroscopic characteristics for its initial management and to take it into account as a differential diagnosis of exophytic lesions. PMID:29732137

Wild-Type Reovirus in Combination With Sargramostim in Treating Younger Patients With High-Grade Relapsed or Refractory Brain Tumors

ClinicalTrials.gov

2018-03-16

Childhood Astrocytoma; Childhood Atypical Teratoid/Rhabdoid Tumor; Diffuse Intrinsic Pontine Glioma; Glioma; Recurrent Childhood Anaplastic Oligodendroglioma; Recurrent Childhood Brain Neoplasm; Recurrent Childhood Glioblastoma; Recurrent Childhood Medulloblastoma; Recurrent Primitive Neuroectodermal Tumor; Refractory Brain Neoplasm

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

Delayed hemorrhage after surgery and radiation in suprasellar pilocytic astrocytomas

PubMed Central

Turel, Mazda K.; Kiehl, Tim-Rasmus; Gentili, Fred

2016-01-01

Delayed intracranial hemorrhage is a rare complication of treatment for central nervous system tumors. This may be secondary to malignant transformation of the tumor or vasculopathy related to radiation therapy (RT). While most reports on radiation-induced vasculopathy in children with optic pathway gliomas are associated with ischemic complications, there are only two reports of hemorrhagic complications in these patients. In both cases, the hemorrhage was asymptomatic and remote from the site of the original tumor but within the field of irradiation. We describe a female patient who underwent surgery for an optico-chiasmatic pilocytic astrocytoma (PA) at the age of 12 followed by RT at the age of 17 for tumor progression. The patient was followed with serial magnetic resonance imaging (MRI) scans showing marginal regression and no subsequent evidence of tumor recurrence, including the most recent MRI done only 6 months before the latest presentation. She then developed a symptomatic intratumoral hemorrhage at the age of 32 for which she underwent emergent surgery. To our knowledge, this is the first report of a nonaneurysmal-delayed hemorrhage within the site of previous surgery, several years after RT for a suprasellar PA. We review literature on delayed vasculopathy following the treatment of pediatric optic pathway gliomas and discuss the possible mechanisms of hemorrhage in our case. These long-term follow-up outcomes add significant insight and have implications in patient management. PMID:27857781

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

C-terminally truncated form of αB-crystallin is associated with IDH1 R132H mutation in anaplastic astrocytoma.

PubMed

Avliyakulov, Nuraly K; Rajavel, Kavitha S; Le, Khanh Minh T; Guo, Lea; Mirsadraei, Leili; Yong, William H; Liau, Linda M; Li, Sichen; Lai, Albert; Nghiemphu, Phioanh L; Cloughesy, Timothy F; Linetsky, Michael; Haykinson, Michael J; Pope, Whitney B

2014-03-01

Malignant gliomas are the most common human primary brain tumors. Point mutation of amino acid arginine 132 to histidine (R132H) in the IDH1 protein leads to an enzymatic gain-of-function and is thought to promote gliomagenesis. Little is known about the downstream effects of the IDH1 mutation on protein expression and how and whether changes in protein expression are involved in tumor formation or propagation. In the current study, we used 2D DIGE (difference gel electrophoresis) and mass spectrometry to analyze differences in protein expression between IDH1(R132H) mutant and wild type anaplastic (grade III) astrocytoma from human brain cancer tissues. We show that expression levels of many proteins are altered in IDH1(R132H) mutant anaplastic astrocytoma. Some of the most over-expressed proteins in the mutants include several forms of αB-crystallin, a small heat-shock and anti-apoptotic protein. αB-crystallin proteins are elevated up to 22-fold in IDH1(R132H) mutant tumors, and αB-crystallin expression appears to be controlled at the post-translational level. We identified the most abundant form of αB-crystallin as a low molecular weight species that is C-terminally truncated. We also found that overexpression of αB-crystallin can be induced by transfecting U251 human glioblastoma cell lines with the IDH1(R132H) mutation. In conclusion, the association of a C-terminally truncated form of αB-crystallin protein with the IDH1(R132H) mutation is a novel finding that could impact apoptosis and stress response in IDH1 mutant glioma.

Absence of IDH1-R132H mutation predicts rapid progression of nonenhancing diffuse glioma in older adults.

PubMed

Olar, Adriana; Raghunathan, Aditya; Albarracin, Constance T; Aldape, Kenneth D; Cahill, Daniel P; Powell, Suzanne Z; Goodman, J Clay; Fuller, Gregory N

2012-06-01

Advanced age and contrast enhancement portend a poor prognosis in diffuse glioma (DG). Diffuse glioma may present as nonenhancing tumors that rapidly progress in weeks to months to a pattern of ring enhancement, characteristic of glioblastoma (GBM). Mutations involving isocitrate dehydrogenase 1 (IDH1) have recently emerged as important diagnostic and prognostic markers in DG. R132H is the most common mutation, expressed in more than 80% of DG and secondary GBM but in less than 10% of primary GBM. Adults older than 50 years with nonenhancing, rapidly progressing DG were identified. A comparison group comprised randomly selected, age-matched patients with nonenhancing, nonprogressing DG. Isocitrate dehydrogenase 1 status was evaluated using anti-IDH1-R132H antibodies (Dianova, Hamburg, Germany). The results were correlated with the clinical outcomes. We identified 4 patients who presented with nonenhancing DG that rapidly progressed to ring-enhancing lesions that were subsequently diagnosed on surgical resection as GBM. This group showed absent IDH1-R132H expression, which is characteristic of primary GBM. The comparison group of 5 patients presented with nonenhancing, nonprogressing DG, and all 5 tumors showed IDH1-R132H expression. In conclusion, negative IDH1-R132H mutation status in nonenhancing DG of older adults is a poor prognostic factor associated with rapid progression to ring-enhancing GBM. The shorter interval of progression and negative IDH1-R132H mutation status suggest a similar molecular pathway as seen in primary GBM. Copyright © 2012 Elsevier Inc. All rights reserved.

Palliative Care Options for a Young Adult Patient with a Diffuse Intrinsic Pontine Glioma.

PubMed

Sison, Julian; Tran, Hung; Margol, Ashley; Tiwari, Nishant; Garcia, Karla M; Cotter, Jennifer; Kiehna, Erin; Olch, Arthur J; Wong, Kenneth

2017-08-18

Diffuse intrinsic pontine gliomas (DIPGs) are rare but devastating brain tumors that occur primarily in children. These gliomas have poor prognoses and present options focus on palliation of symptoms and prolongation of life. Here, we present a case of a 16-year-old female diagnosed with a DIPG whose age group has been mostly left out of discussions regarding psychosocial support options. This report is meant to start a conversation about the different support options available at our institution that have shown promising results in the literature for palliative care applications. These options can include camps for patients with brain tumors, psychological counseling, the Ronald McDonald House, and other psychosocial programs. Many of these programs can be tailored to meet the specific needs of adolescent and young adult (AYA) patients and will hopefully be integrated into a comprehensive palliative care regimen in future studies.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Teng, Chih-Chuan; Institute of Basic Medicine Science, National Cheng Kung University, Tainan, Taiwan; Kuo, Hsing-Chun

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{supmore » 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.« less

Subependymal giant cell astrocytoma: clinical and neuroimaging features of four cases.

PubMed

Nishio, S; Morioka, T; Suzuki, S; Kira, R; Mihara, F; Fukui, M

2001-01-01

The clinical history, neuroimaging features, treatments, and outcome of 4 patients with histologically verified subependymal giant cell astrocytomas (SEGA) were retrospectively reviewed. The average age at the time of surgery was 13.3 years. Headache related to raised intracranial pressure was the first and only sign in 2 patients, with the remaining 2 being admitted because of sequential neuroimaging studies over several years revealing the growth of 'subependymal nodules' into intraventricular tumours. In each case the tumour was in the region of Monro's foramen and was associated with ventricular dilatation. On computed tomography (CT), multiple subependymal nodules were found in 3 patients, and these well circumscribed isodense SEGAs were markedly enhanced by contrast medium. On magnetic resonance imaging (MRI), which was obtained in 3 patients, 2 SEGAs were isointense with the cerebral cortex and one with the white matter on T1-weighted images, and on T2-weighted images, 2 were isointense with the cortex and one with the white matter. At surgery the tumours appeared to originate from the inferolateral wall of the lateral ventricle in the region of the head of the caudate nuclei. Total macroscopic removal was achieved in 3 patients, and subtotal removal in one patient. Follow up ranged from 4.6 to 13.2 years, and all patients have exhibited similar physical and mental conditions to preoperative. So far there has been no evidence of any recurrences. The diagnosis and the surgical indications for SEGA are discussed, with periodic monitoring with neuroimaging studies being recommended even for asymptomatic patients with 'subependymal nodules'.

Immunohistochemical comparative analysis of GFAP, MAP - 2, NOGO - A, OLIG - 2 and WT - 1 expression in WHO 2016 classified neuroepithelial tumours and their prognostic value.

PubMed

Schwab, David Emanuel; Lepski, Guilherme; Borchers, Christian; Trautmann, Katrin; Paulsen, Frank; Schittenhelm, Jens

2018-01-01

Immunohistochemistry is routinely used in differential diagnosis of tumours of the central nervous system (CNS). The latest 2016 WHO 2016 revision now includes molecular data such as IDH mutation and 1p/19q codeletion thus restructuring glioma classification. Direct comparative information between commonly used immunohistochemical markers for glial tumours GFAP, MAP - 2, NOGO - A, OLIG - 2 and WT - 1 concerning quality and quantity of expression and their relation to the new molecular markers are lacking. We therefore compared the immunohistochemical staining results of all five antibodies in 34 oligodendrogliomas, 106 ependymomas and 423 astrocytic tumours. GFAP expression was reduced in cases with higher WHO grade, oligodendroglial differentiation and in IDH wildtype diffuse astrocytomas. By contrast MAP - 2 expression was significantly increased in diffuse astrocytomas with IDH mutation, while NOGO - A expression was not associated with any molecular marker. WT - 1 expression was significantly decreased in tumours with IDH mutation and ATRX loss. OLIG - 2 was increased in IDH-mutant grade II astrocytomas and in cases with higher proliferation rate. In univariate survival analysis high WT - 1 expression was significantly associated with worse outcome in diffuse astrocytic tumours (log rank p < 0.0001; n = 211; median time: 280 days vs 562 days). None of the markers was prognostic in multivariate survival analysis. Among the evaluated markers MAP - 2, OLIG - 2 and WT - 1 showed the best potential to separate between glioma entities and can be recommended for a standardized immunohistochemical panel. Copyright © 2017 Elsevier GmbH. All rights reserved.

Thinking outside the shunt-sterile CSF malabsorption in pilocytic astrocytomas: case series and review of the literature.

PubMed

Johnson, J A; O'Halloran, P J; Crimmins, D; Caird, J

2016-11-01

Ventriculoperitoneal (VP) shunt insertion is the most common cerebrospinal fluid (CSF) diversionary procedure used for the treatment of chronic hydrocephalus. Sterile CSF ascites is a rare complication of VP shunt insertion. This can arise from either an overproduction of CSF or inadequate filtration of CSF at the level of the peritoneum. By either mechanism, the development of CSF ascites requires an intact VP shunt. The authors discuss two paediatric cases diagnosed with suprasellar pilocytic astrocytomas treated with platinum-based chemotherapy, who subsequently developed sterile CSF ascites. We review the literature with regard to CSF malabsorption and discuss it as a contributing factor to shunt malfunction. CSF malabsorption with resultant ascites is a rare complication of VP shunting with many etiologies. Two common predisposing factors included the use of platinum-based chemotherapeutic agents, as well as the specific neuropathology. Further analysis of these two entities is needed in order to elucidate their role in contributing to the development of CSF ascites in this patient cohort.

Abnormal cholesterol is associated with prefrontal white matter abnormalities among obese adults, a diffusion tensor imaging study

PubMed Central

Cohen, Jessica I.; Cazettes, Fanny; Convit, Antonio

2011-01-01

The brain is the most cholesterol-rich organ in the body. Although most of the cholesterol in the brain is produced endogenously, some studies suggest that systemic cholesterol may be able to enter the brain. We investigated whether abnormal cholesterol profiles correlated with diffusion-tensor-imaging-based estimates of white matter microstructural integrity of lean and overweight/obese (o/o) adults. Twenty-two lean and 39 obese adults underwent magnetic resonance imaging, kept a 3-day food diary, and had a standardized assessment of fasting blood lipids. The lean group ate less cholesterol rich food than o/o although both groups ate equivalent servings of food per day. Voxelwise correlational analyses controlling for age, diabetes, and white matter hyperintensities, resulted in two significant clusters of negative associations between abnormal cholesterol profile and fractional anisotropy, located in the left and right prefrontal lobes. When the groups were split, the lean subjects showed no associations, whereas the o/o group expanded the association to three significant clusters, still in the frontal lobes. These findings suggest that cholesterol profile abnormalities may explain some of the reductions in white matter microstructural integrity that are reported in obesity. PMID:22163070

Lévy-like diffusion in eye movements during spoken-language comprehension.

PubMed

Stephen, Damian G; Mirman, Daniel; Magnuson, James S; Dixon, James A

2009-05-01

This study explores the diffusive properties of human eye movements during a language comprehension task. In this task, adults are given auditory instructions to locate named objects on a computer screen. Although it has been convention to model visual search as standard Brownian diffusion, we find evidence that eye movements are hyperdiffusive. Specifically, we use comparisons of maximum-likelihood fit as well as standard deviation analysis and diffusion entropy analysis to show that visual search during language comprehension exhibits Lévy-like rather than Gaussian diffusion.

Lévy-like diffusion in eye movements during spoken-language comprehension

NASA Astrophysics Data System (ADS)

Stephen, Damian G.; Mirman, Daniel; Magnuson, James S.; Dixon, James A.

2009-05-01

This study explores the diffusive properties of human eye movements during a language comprehension task. In this task, adults are given auditory instructions to locate named objects on a computer screen. Although it has been convention to model visual search as standard Brownian diffusion, we find evidence that eye movements are hyperdiffusive. Specifically, we use comparisons of maximum-likelihood fit as well as standard deviation analysis and diffusion entropy analysis to show that visual search during language comprehension exhibits Lévy-like rather than Gaussian diffusion.

Spatial dynamics of a population with stage-dependent diffusion

NASA Astrophysics Data System (ADS)

Azevedo, F.; Coutinho, R. M.; Kraenkel, R. A.

2015-05-01

We explore the spatial dynamics of a population whose individuals go through life stages with very different dispersal capacities. We model it through a system of partial differential equations of the reaction-diffusion kind, with nonlinear diffusion terms that may depend on population density and on the stage. This model includes a few key biological ingredients: growth and saturation, life stage structure, small population effects, and diffusion dependent on the stage. In particular, we consider that adults exhibit two distinct classes: one highly mobile and the other less mobile but with higher fecundity rate, and the development of juveniles into one or the other depends on population density. We parametrize the model with estimated parameters of an insect species, the brown planthopper. We focus on a situation akin to an invasion of the species in a new habitat and find that the front of invasion is led by the most mobile adult class. We also show that the trade-off between dispersal and fecundity leads to invasion speed attaining its maximum at an intermediate value of the diffusion coefficient of the most mobile class.

Changes in diffusion path length with old age in diffuse optical tomography

NASA Astrophysics Data System (ADS)

Bonnéry, Clément; Leclerc, Paul-Olivier; Desjardins, Michèle; Hoge, Rick; Bherer, Louis; Pouliot, Philippe; Lesage, Frédéric

2012-05-01

Diffuse, optical near infrared imaging is increasingly being used in various neurocognitive contexts where changes in optical signals are interpreted through activation maps. Statistical population comparison of different age or clinical groups rely on the relative homogeneous distribution of measurements across subjects in order to infer changes in brain function. In the context of an increasing use of diffuse optical imaging with older adult populations, changes in tissue properties and anatomy with age adds additional confounds. Few studies investigated these changes with age. Duncan et al. measured the so-called diffusion path length factor (DPF) in a large population but did not explore beyond the age of 51 after which physiological and anatomical changes are expected to occur [Pediatr. Res. 39(5), 889-894 (1996)]. With increasing interest in studying the geriatric population with optical imaging, we studied changes in tissue properties in young and old subjects using both magnetic resonance imaging (MRI)-guided Monte-Carlo simulations and time-domain diffuse optical imaging. Our results, measured in the frontal cortex, show changes in DPF that are smaller than previously measured by Duncan et al. in a younger population. The origin of these changes are studied using simulations and experimental measures.

Nestin expression in neuroepithelial tumors.

PubMed

Schiffer, Davide; Manazza, Andrea; Tamagno, Ilaria

2006-05-29

Nestin is a marker of early stages of neurocytogenesis. It has been studied in 50 neuroepithelial tumors, mostly gliomas of different malignancy grades, by immunohistochemistry, immunofluorescence, immunoblotting, and confocal microscopy and compared with GFAP and Vimentin. As an early marker of differentiation, Nestin is almost not expressed in diffuse astrocytomas, variably expressed in anaplastic astrocytomas and strongly and irregularly expressed in glioblastomas. Negative in oligodendrogliomas, it stains ependymomas and shows a gradient of expression in pilocytic astrocytomas. In glioblastomas, Nestin distribution does not completely correspond to that of GFAP and Vimentin with which its expression varies in tumor cells in a complementary way, as confirmed by confocal microscopy. Tumor cells can thus either derive from or differentiate toward the neurocytogenetic stages. Hypothetically, they could be put in relation with radial glia where during embriogenesis the three antigens are successively expressed. Completely negative cells of invasive or recurrent glioblastomas may represent malignant selected clones after accumulation of mutations or early stem cells not expressing antigens.

The effects of ageing on mouse muscle microstructure: a comparative study of time-dependent diffusion MRI and histological assessment.

PubMed

Porcari, Paola; Hall, Matt G; Clark, Chris A; Greally, Elizabeth; Straub, Volker; Blamire, Andrew M

2018-03-01

The investigation of age-related changes in muscle microstructure between developmental and healthy adult mice may help us to understand the clinical features of early-onset muscle diseases, such as Duchenne muscular dystrophy. We investigated the evolution of mouse hind-limb muscle microstructure using diffusion imaging of in vivo and in vitro samples from both actively growing and mature mice. Mean apparent diffusion coefficients (ADCs) of the gastrocnemius and tibialis anterior muscles were determined as a function of diffusion time (Δ), age (7.5, 22 and 44 weeks) and diffusion gradient direction, applied parallel or transverse to the principal axis of the muscle fibres. We investigated a wide range of diffusion times with the goal of probing a range of diffusion lengths characteristic of muscle microstructure. We compared the diffusion time-dependent ADC of hind-limb muscles with histology. ADC was found to vary as a function of diffusion time in muscles at all stages of maturation. Muscle water diffusivity was higher in younger (7.5 weeks) than in adult (22 and 44 weeks) mice, whereas no differences were observed between the older ages. In vitro data showed the same diffusivity pattern as in vivo data. The highlighted differences in diffusion properties between young and mature muscles suggested differences in underlying muscle microstructure, which were confirmed by histological assessment. In particular, although diffusion was more restricted in older muscle, muscle fibre size increased significantly from young to adult age. The extracellular space decreased with age by only ~1%. This suggests that the observed diffusivity differences between young and adult muscles may be caused by increased membrane permeability in younger muscle associated with properties of the sarcolemma. Copyright © 2018 John Wiley & Sons, Ltd.

Acrylamide-induced apoptosis in rat primary astrocytes and human astrocytoma cell lines.

PubMed

Lee, Jiann-Gwu; Wang, Yan-Shiu; Chou, Chin-Cheng

2014-06-01

This study aimed to evaluate the acrylamide (ACR)-induced apoptotic effects on rat primary astrocytes and three human astrocytoma-derived cell lines (U-1240 MG, U-87 MG, and U-251 MG). As determined through the MTT assay, treatment with 1 and 2 mM ACR for 24-72 h resulted in decreased cell viability in all cells. Decreases in cell viability could be blocked in all cells with the exception of U-251 MG cells by Z-DEVD FMK. ACR-induced dose-dependent apoptotic effects were also demonstrated by increases in the sub-G1 phase cell population in all cells. The decreased expressions of pro-caspase 3, 8, and 9 and the interruption of the mitochondrial membrane potential were observed in all cells. Exposure to 2 mM ACR for 48 h resulted in increased Bax/Bcl-2 ratios in primary astrocytes and U-87 MG cells, whereas the overexpression of Bcl-2 was observed in U-1240 MG and U-251 MG cells. The ACR-induced increases in the levels of p53 and pp53 in primary astrocytes could be attenuated by caffeine. These results suggest the existence of a common apoptotic pathway among all cell types and that U-87 MG cells may be a suitable substitute in vitro model for primary astrocytes in future studies on ACR-induced neurotoxicity. Copyright © 2014 Elsevier Ltd. All rights reserved.

The case for DNA methylation based molecular profiling to improve diagnostic accuracy for central nervous system embryonal tumors (not otherwise specified) in adults.

PubMed

Halliday, Gail C; Junckerstorff, Reimar C; Bentel, Jacqueline M; Miles, Andrew; Jones, David T W; Hovestadt, Volker; Capper, David; Endersby, Raelene; Cole, Catherine H; van Hagen, Tom; Gottardo, Nicholas G

2018-01-01

Central nervous system primitive neuro-ectodermal tumors (CNS-PNETs), have recently been re-classified in the most recent 2016 WHO Classification into a standby catch all category, "CNS Embryonal Tumor, not otherwise specified" (CNS embryonal tumor, NOS) based on epigenetic, biologic and histopathologic criteria. CNS embryonal tumors (NOS) are a rare, histologically and molecularly heterogeneous group of tumors that predominantly affect children, and occasionally adults. Diagnosis of this entity continues to be challenging and the ramifications of misdiagnosis of this aggressive class of brain tumors are significant. We report the case of a 45-year-old woman who was diagnosed with a central nervous system embryonal tumor (NOS) based on immunohistochemical analysis of the patient's tumor at diagnosis. However, later genome-wide methylation profiling of the diagnostic tumor undertaken to guide treatment, revealed characteristics most consistent with IDH-mutant astrocytoma. DNA sequencing and immunohistochemistry confirmed the presence of IDH1 and ATRX mutations resulting in a revised diagnosis of high-grade small cell astrocytoma, and the implementation of a less aggressive treatment regime tailored more appropriately to the patient's tumor type. This case highlights the inadequacy of histology alone for the diagnosis of brain tumours and the utility of methylation profiling and integrated genomic analysis for the diagnostic verification of adults with suspected CNS embryonal tumor (NOS), and is consistent with the increasing realization in the field that a combined diagnostic approach based on clinical, histopathological and molecular data is required to more accurately distinguish brain tumor subtypes and inform more effective therapy. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Regulation of glutamate in cultures of human monocytic THP-1 and astrocytoma U-373 MG cells.

PubMed

Klegeris, A; Walker, D G; McGeer, P L

1997-09-01

Glutamate, an excitatory neurotransmitter, is neurotoxic at high concentrations. Neuroglial cells, including astrocytes and microglia, play an important role in regulating its extracellular levels. Cultured human monocytic THP-1 cells increased their glutamate secretion following 18 and 68 h exposure to the inflammatory mediators zymosan, phorbol myristate acetate (PMA), lipopolysaccharide, interferon-gamma, tumor-necrosis factor-alpha and interleukin-1beta. Cultured astrocytoma U-373 MG cells increased their glutamate secretion following similar exposure to zymosan and PMA. DL-Alpha-aminopimelic acid, an inhibitor of the glutamate secretion system, reduced extracellular glutamate in both cell culture systems, while the high-affinity glutamate uptake inhibitors D-Aspartic acid, DL-threo-beta-hydroxyaspartic acid and L-trans-pyrrolidine-2,4-dicarboxylic acid increased extracellular glutamate in U-373 MG, but not THP-1 cell cultures. In co-cultures of THP-1 and U-373 MG cells, extracellular glutamate levels were increased significantly by the Alzheimer beta-amyloid peptide (1-40) and were decreased significantly by the anti-inflammatory drug dexamethasone. These data indicate that inflammatory stimuli may increase extracellular glutamate while antiinflammatory drugs decrease it.

Cytotoxicity Effects of Different Surfactant Molecules Conjugated to Carbon Nanotubes on Human Astrocytoma Cells

NASA Astrophysics Data System (ADS)

Dong, Lifeng; Witkowski, Colette M.; Craig, Michael M.; Greenwade, Molly M.; Joseph, Katherine L.

2009-12-01

Phase contrast and epifluorescence microscopy were utilized to monitor morphological changes in human astrocytoma cells during a time-course exposure to single-walled carbon nanotube (SWCNT) conjugates with different surfactants and to investigate sub-cellular distribution of the nanotube conjugates, respectively. Experimental results demonstrate that cytotoxicity of the nanotube/surfactant conjugates is related to the toxicity of surfactant molecules attached on the nanotube surfaces. Both sodium dodecyl sulfate (SDS) and sodium dodecylbenzene sulfonate (SDBS) are toxic to cells. Exposure to CNT/SDS conjugates (0.5 mg/mL) for less than 5 min caused changes in cell morphology resulting in a distinctly spherical shape compared to untreated cells. In contrast, sodium cholate (SC) and CNT/SC did not affect cell morphology, proliferation, or growth. These data indicate that SC is an environmentally friendly surfactant for the purification and dispersion of SWCNTs. Epifluorescence microscopy analysis of CNT/DNA conjugates revealed distribution in the cytoplasm of cells and did not show adverse effects on cell morphology, proliferation, or viability during a 72-h incubation. These observations suggest that the SWCNTs could be used as non-viral vectors for diagnostic and therapeutic molecules across the blood-brain barrier to the brain and the central nervous system.

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

2017-07-01

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. © 2017 Blackwell Verlag GmbH.

Modeling of Diffuse-Diffuse Photon Coupling via a Nonscattering Region: a Comparative Study

NASA Astrophysics Data System (ADS)

Lee, Jae Hoon; Kim, Seunghwan; Kim, Youn Tae

2004-06-01

It is well established that diffusion approximation is valid for light propagation in highly scattering media, but it breaks down in nonscattering regions. The previous methods that manipulate nonscattering regions are essentially boundary-to-boundary coupling (BBC) methods through a nonscattering void region based on the radiosity theory. We present a boundary-to-interior coupling (BIC) method. BIC is based on the fact that the collimated pencil beam incident on the medium can be replaced by an isotropic point source positioned at one reduced scattering length inside the medium from an illuminated point. A similar replacement is possible for the nondiffuse lights that enter the diffuse medium through the void, and it is formulated as the BIC method. We implemented both coupling methods using the finite element method (FEM) and tested for the circle with a void gap and for a four-layer adult head model. For mean time of flight, the BIC shows better agreement with Monte Carlo (MC) simulation results than BBC. For intensity, BIC shows a comparable match with MC data compared with that of BBC. The effect of absorption of the clear layer in the adult head model was investigated. Both mean time and intensity decrease as absorption of the clear layer increases.

Modeling of diffuse-diffuse photon coupling via a nonscattering region: a comparative study.

PubMed

Lee, Jae Hoon; Kim, Seunghwan; Kim, Youn Tae

2004-06-20

It is well established that diffusion approximation is valid for light propagation in highly scattering media, but it breaks down in nonscattering regions. The previous methods that manipulate nonscattering regions are essentially boundary-to-boundary coupling (BBC) methods through a nonscattering void region based on the radiosity theory. We present a boundary-to-interior coupling (BIC) method. BIC is based on the fact that the collimated pencil beam incident on the medium can be replaced by an isotropic point source positioned at one reduced scattering length inside the medium from an illuminated point. A similar replacement is possible for the nondiffuse lights that enter the diffuse medium through the void, and it is formulated as the BIC method. We implemented both coupling methods using the finite element method (FEM) and tested for the circle with a void gap and for a four-layer adult head model. For mean time of flight, the BIC shows better agreement with Monte Carlo (MC) simulation results than BBC. For intensity, BIC shows a comparable match with MC data compared with that of BBC. The effect of absorption of the clear layer in the adult head model was investigated. Both mean time and intensity decrease as absorption of the clear layer increases.

Novel glioblastoma markers with diagnostic and prognostic value identified through transcriptome analysis.

PubMed

Reddy, Sreekanth P; Britto, Ramona; Vinnakota, Katyayni; Aparna, Hebbar; Sreepathi, Hari Kishore; Thota, Balaram; Kumari, Arpana; Shilpa, B M; Vrinda, M; Umesh, Srikantha; Samuel, Cini; Shetty, Mitesh; Tandon, Ashwani; Pandey, Paritosh; Hegde, Sridevi; Hegde, A S; Balasubramaniam, Anandh; Chandramouli, B A; Santosh, Vani; Kondaiah, Paturu; Somasundaram, Kumaravel; Rao, M R Satyanarayana

2008-05-15

Current methods of classification of astrocytoma based on histopathologic methods are often subjective and less accurate. Although patients with glioblastoma have grave prognosis, significant variability in patient outcome is observed. Therefore, the aim of this study was to identify glioblastoma diagnostic and prognostic markers through microarray analysis. We carried out transcriptome analysis of 25 diffusely infiltrating astrocytoma samples [WHO grade II--diffuse astrocytoma, grade III--anaplastic astrocytoma, and grade IV--glioblastoma (GBM)] using cDNA microarrays containing 18,981 genes. Several of the markers identified were also validated by real-time reverse transcription quantitative PCR and immunohistochemical analysis on an independent set of tumor samples (n = 100). Survival analysis was carried out for two markers on another independent set of retrospective cases (n = 51). We identified several differentially regulated grade-specific genes. Independent validation by real-time reverse transcription quantitative PCR analysis found growth arrest and DNA-damage-inducible alpha (GADD45alpha) and follistatin-like 1 (FSTL1) to be up-regulated in most GBMs (both primary and secondary), whereas superoxide dismutase 2 and adipocyte enhancer binding protein 1 were up-regulated in the majority of primary GBM. Further, identification of the grade-specific expression of GADD45alpha and FSTL1 by immunohistochemical staining reinforced our findings. Analysis of retrospective GBM cases with known survival data revealed that cytoplasmic overexpression of GADD45alpha conferred better survival while the coexpression of FSTL1 with p53 was associated with poor survival. Our study reveals that GADD45alpha and FSTLI are GBM-specific whereas superoxide dismutase 2 and adipocyte enhancer binding protein 1 are primary GBM-specific diagnostic markers. Whereas GADD45alpha overexpression confers a favorable prognosis, FSTL1 overexpression is a hallmark of poor prognosis in GBM

Suggestions for a Realistic Adult Education Policy.

ERIC Educational Resources Information Center

Coombs, Philip H.

1985-01-01

Five sets of implementation problems of adult education are examined: (1) diffusion of organizational responsibility, (2) lack of an integrated approach, (3) aims and priorities of adult education and the lack of learner motivation, (4) resource requirements, and (5) the imposition by formal education of constraints upon adult education. (RM)

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

PubMed Central

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. PMID:23826410

An analysis of the prognostic value of IDH1 (isocitrate dehydrogenase 1) mutation in Polish glioma patients.

PubMed

Lewandowska, Marzena Anna; Furtak, Jacek; Szylberg, Tadeusz; Roszkowski, Krzysztof; Windorbska, Wiesława; Rytlewska, Joanna; Jóźwicki, Wojciech

2014-02-01

IDH1 (isocitrate dehydrogenase 1) is a potential biomarker and drug target. Genomic and epigenetic data on astrocytoma have demonstrated that the IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype. Furthermore, recent studies have also indicated that a mutant IDH1 inhibitor induced demethylation of histone H3K9me3 and expression of genes associated with gliogenic differentiation. As the presence of the p.R132H mutation in the IDH1 gene seems to be a more powerful prognostic marker than O(6)-methylguanine-DNA methyltransferase promoter status, we evaluated the presence of IDH1 mutation in Polish patients with astrocytoma, glioblastoma, oligoastrocytoma, ganglioglioma, oligodendroglioma, and ependymoma. The IDH1 mutation status at codon 132 was determined using a mouse monoclonal antibody specific for the R132H mutation, direct sequencing, and Co-amplification at Lower Denaturation Temperature (COLD) polymerase chain reaction (PCR) high-resolution melting-curve analysis (HRM). Wild-type (WT) IDH1 was detected in cases with a World Health Organization (WHO) grade I astrocytoma. The IDH1 c.G395A; p.R132H mutation was observed in 56 and 94 % of grade II and grade III astrocytoma cases, respectively. Significant differences in the median overall survival were observed in astrocytoma patients grouped on the basis of the presence of IDH1 mutation: survival was 24 months longer in grade II astrocytoma and 12 months longer in glioblastoma. Overall survival was compared between grade II astrocytoma patients with low or high expression of the mutant protein. Interestingly, lower R132H expression correlated with better overall survival. Our results indicate the usefulness of assessing the R132H IDH1 mutation in glioma patients: the presence or absence of the R132H mutation can help pathologists to distinguish pilocytic astrocytomas (IDH1 WT) from diffuse ones (R132H IDH1/WT). Moreover, low IDH1 p.R132H expression was related to better prognosis

Diffusion of Technology: Frequency of Use for Younger and Older Adults

PubMed Central

Olson, Katherine E.; O’Brien, Marita A.; Rogers, Wendy A.; Charness, Neil

2012-01-01

Objectives When we think of technology-savvy consumers, older adults are typically not the first persons that come to mind. The common misconception is that older adults do not want to use or cannot use technology. But for an increasing number of older adults, this is not true (Pew Internet and American Life Project, 2003). Older adults do use technologies similar to their younger counterparts, but perhaps at different usage rates. Previous research has identified that there may be subgroups of older adults, “Silver Surfers”, whose adoption patterns mimic younger adults (Pew Internet and American Life Project, 2003). Much of the previous research on age-related differences in technology usage has only investigated usage broadly -- from a “used” or “not used” standpoint. The present study investigated age-related differences in overall usage of technologies, as well as frequency of technology usage (i.e., never, occasional, or frequent). Methods The data were gathered through a questionnaire from younger adults (N=430) and older adults (N=251) in three geographically separate and ethnically diverse areas of the United States. Results We found that younger adults use a greater breadth of technologies than older adults. However, age-related differences in usage and the frequency of use depend on the technology domain. Conclusion This paper presents technology usage and frequency data to highlight age-related differences and similarities. The results provide insights into older and younger adults’ technology-use patterns, which in turn provide a basis for expectations about knowledge differences. Designers and trainers can benefit from understanding experience and knowledge differences. PMID:22685360

Low values of 5-hydroxymethylcytosine (5hmC), the "sixth base," are associated with anaplasia in human brain tumors.

PubMed

Kraus, Theo F J; Globisch, Daniel; Wagner, Mirko; Eigenbrod, Sabina; Widmann, David; Münzel, Martin; Müller, Markus; Pfaffeneder, Toni; Hackner, Benjamin; Feiden, Wolfgang; Schüller, Ulrich; Carell, Thomas; Kretzschmar, Hans A

2012-10-01

5-Methylcytosine (5 mC) in genomic DNA has important epigenetic functions in embryonic development and tumor biology. 5-Hydroxymethylcytosine (5 hmC) is generated from 5 mC by the action of the TET (Ten-Eleven-Translocation) enzymes and may be an intermediate to further oxidation and finally demethylation of 5 mC. We have used immunohistochemistry (IHC) and isotope-based liquid chromatography mass spectrometry (LC-MS) to investigate the presence and distribution of 5 hmC in human brain and brain tumors. In the normal adult brain, IHC identified 61.5% 5 hmC positive cells in the cortex and 32.4% 5 hmC in white matter (WM) areas. In tumors, positive staining of cells ranged from 1.1% in glioblastomas (GBMs) (WHO Grade IV) to 8.9% in Grade I gliomas (pilocytic astrocytomas). In the normal adult human brain, LC-MS also showed highest values in cortical areas (1.17% 5 hmC/dG [deoxyguanosine]), in the cerebral WM we measured around 0.70% 5 hmC/dG. levels were related to tumor differentiation, ranging from lowest values of 0.078% 5 hmC/dG in GBMs (WHO Grade IV) to 0.24% 5 hmC/dG in WHO Grade II diffuse astrocytomas. 5 hmC measurements were unrelated to 5 mC values. We find that the number of 5 hmC positive cells and the amount of 5 hmC/dG in the genome that has been proposed to be related to pluripotency and lineage commitment in embryonic stem cells is also associated with brain tumor differentiation and anaplasia. Copyright © 2012 UICC.

Atypical white-matter microstructure in congenitally deaf adults: A region of interest and tractography study using diffusion-tensor imaging.

PubMed

Karns, Christina M; Stevens, Courtney; Dow, Mark W; Schorr, Emily M; Neville, Helen J

2017-01-01

Considerable research documents the cross-modal reorganization of auditory cortices as a consequence of congenital deafness, with remapped functions that include visual and somatosensory processing of both linguistic and nonlinguistic information. Structural changes accompany this cross-modal neuroplasticity, but precisely which specific structural changes accompany congenital and early deafness and whether there are group differences in hemispheric asymmetries remain to be established. Here, we used diffusion tensor imaging (DTI) to examine microstructural white matter changes accompanying cross-modal reorganization in 23 deaf adults who were genetically, profoundly, and congenitally deaf, having learned sign language from infancy with 26 hearing controls who participated in our previous fMRI studies of cross-modal neuroplasticity. In contrast to prior literature using a whole-brain approach, we introduce a semiautomatic method for demarcating auditory regions in which regions of interest (ROIs) are defined on the normalized white matter skeleton for all participants, projected into each participants native space, and manually constrained to anatomical boundaries. White-matter ROIs were left and right Heschl's gyrus (HG), left and right anterior superior temporal gyrus (aSTG), left and right posterior superior temporal gyrus (pSTG), as well as one tractography-defined region in the splenium of the corpus callosum connecting homologous left and right superior temporal regions (pCC). Within these regions, we measured fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity (AD), and white-matter volume. Congenitally deaf adults had reduced FA and volume in white matter structures underlying bilateral HG, aSTG, pSTG, and reduced FA in pCC. In HG and pCC, this reduction in FA corresponded with increased RD, but differences in aSTG and pSTG could not be localized to alterations in RD or AD. Direct statistical tests of hemispheric asymmetries in these

Vorinostat and Bortezomib in Treating Young Patients With Refractory or Recurrent Solid Tumors, Including Central Nervous System Tumors and Lymphoma

ClinicalTrials.gov

2013-07-01

Childhood Burkitt Lymphoma; Childhood Central Nervous System Choriocarcinoma; Childhood Central Nervous System Germ Cell Tumor; Childhood Central Nervous System Germinoma; Childhood Central Nervous System Mixed Germ Cell Tumor; Childhood Central Nervous System Teratoma; Childhood Central Nervous System Yolk Sac Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Medulloepithelioma; Childhood Meningioma; Childhood Mixed Glioma; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Childhood Oligodendroglioma; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Central Nervous System Embryonal Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Unspecified Childhood Solid Tumor, Protocol Specific

A Diffusion Model Analysis of Episodic Recognition in Individuals with a Family History for Alzheimer Disease: The Adult Children Study

PubMed Central

Aschenbrenner, Andrew J.; Balota, David A.; Gordon, Brian A.; Ratcliff, Roger; Morris, John C.

2015-01-01

Objective A family history of Alzheimer disease (AD) increases the risk of developing AD and can influence the accumulation of well-established AD biomarkers. There is some evidence that family history can influence episodic memory performance even in cognitively normal individuals. We attempted to replicate the effect of family history on episodic memory and used a specific computational model of binary decision making (the diffusion model) to understand precisely how family history influences cognition. Finally, we assessed the sensitivity of model parameters to family history controlling for standard neuropsychological test performance. Method Across two experiments, cognitively healthy participants from the Adult Children Study completed an episodic recognition test consisting of high and low frequency words. The diffusion model was applied to decompose accuracy and reaction time into latent parameters which were analyzed as a function of family history. Results In both experiments, individuals with a family history of AD exhibited lower recognition accuracy and this occurred in the absence of an apolipoprotein E (APOE) ε4 allele. The diffusion model revealed this difference was due to changes in the quality of information accumulation (the drift rate) and not differences in response caution or other model parameters. This difference remained after controlling for several standard neuropsychological tests. Conclusions These results confirm that the presence of a family history of AD confers a subtle cognitive deficit in episodic memory as reflected by decreased drift rate that cannot be attributed to APOE. This measure may serve as a novel cognitive marker of preclinical AD. PMID:26192539

Trapped ventricle after laser ablation of a subependymal giant cell astrocytoma complicated by intraventricular gadolinium extravasation: case report.

PubMed

Karsy, Michael; Patel, Daxa M; Bollo, Robert J

2018-05-01

Magnetic resonance imaging-guided stereotactic laser ablation of intracranial targets, including brain tumors, has expanded dramatically over the past decade, but there have been few reports of complications, especially those occurring in a delayed fashion. Laser ablation of subependymal giant cell astrocytomas (SEGAs) is an attractive alternative to maintenance immunotherapy in some children with tuberous sclerosis complex (TSC); however, the effect of treatment on disease progression and the nature and frequency of potential complications remains largely unknown. The authors report the case of a 5-year-old boy with TSC who underwent stereotactic laser ablation of a SEGA at the right foramen of Monro on 2 separate occasions. After the second ablation, immediate posttreatment MRI revealed gadolinium extravasation from the tumor into the lateral ventricle. Nine months later, the patient presented with papilledema and delayed obstructive hydrocephalus secondary to intraventricular adhesions causing a trapped right lateral ventricle. This was successfully treated with endoscopic septostomy. The authors discuss the potential cause and clinical management of a delayed complication not previously reported after a relatively novel surgical therapy.

Magnetic resonance diffusion tensor imaging of optic nerve and optic radiation in healthy adults at 3T.

PubMed

Sun, Hong-Hong; Wang, Dong; Zhang, Qiu-Juan; Bai, Zhi-Lan; He, Ping

2013-01-01

To investigate the diffusion characteristics of water of optic nerve and optic radiation in healthy adults and its related factors by diffusion tensor imaging (DTI) at 3T. A total of 107 healthy volunteers performed head conventional MRI and bilateral optic nerve and optic radiation DTI. The primary data of DTI was processed by post-processing software of DTI studio 2.3, obtaining fractional anisotropy value, mean diffusivity value, principal engine value, orthogonal engine value by measuring, and analyzed by the SPSS13.0 statistical software. The bilateral optic nerve and optic radiation fibers presented green color in directional encoded color (DEC) maps and presented high signal in fractional anisotropy (FA) maps. The FA value of the left optic nerve was 0.598±0.069 and the right was 0.593±0.065; the mean diffusivity (MD) value of the left optic nerve was (1.324±0.349)×10(-3)mm(2)/s and the right was (1.312±0.350)×10(-3)mm(2)/s; the principal engine value (λ‖) of the left optic nerve was (2.297±0.522)×10(-3)mm(2)/s and the right was (2.277±0.526)×10(-3)mm(2)/s; the orthogonal engine value (λ⊥) of the left optic nerve was (0.838±0.285)×10(-3)mm(2)/s and the right was (0.830±0.280)×10(-3)mm(2)/s; the FA value of the left optic radiation was 0.636±0.057 and the right was 0.628±0.056; the mean diffusivity (MD) value of the left optic radiation was (0.907±0.103)×10(-3)mm(2)/s and the right was (0.889±0.125)×10(-3)mm(2)/s; the principal eigenvalue (λ‖) of the left optic radiation was (1.655±0.210)×10(-3)mm(2)/s and the right was (1.614±0.171)×10(-3)mm(2)/s; the orthogonal enginvalue (λ⊥) of the left optic radiation was (0.531±0.103)×10(-3)mm(2)/s and the right was (0.524±0.152)×10(-3)mm(2)/s. There was no obvious difference between the FA, MD, λ‖, λ⊥ of the bilateral optic radiation and the bilateral optic nerve (P>0.05) and no obvious difference between male and female group. The FA, MD, λ‖, λ⊥ of the bilateral

Monosaccharide uptake by erythrocytes of the embryonic and adult chicken.

PubMed

Ingermann, R L; Stock, M K; Metcalfe, J; Bissonnette, J M

1985-01-01

Rates of monosaccharide uptake by adult and 10-18 day old embryonic chicken erythrocytes were quantitated. The rate of carrier-mediated, stereospecific transport decreased 28% from day 10 to day 14 of incubation and was unchanged thereafter. At no time, however, did the rate of carrier-mediated transport by embryonic erythrocytes differ significantly from that of the adult cells. The rate of transfer by simple diffusion was 3-5 fold faster in embryonic than in adult erythrocytes. Uptake by simple diffusion decreased slightly as the embryo developed. Chronic hyperoxic incubation (70% O2) had little influence on total monosaccharide uptake by embryonic erythrocytes.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Godin, Fabienne; Villette, Sandrine; Vallee, Beatrice

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 andmore » 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).« less

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.

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

PubMed

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

2017-05-01

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

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

Fractional Diffusion Equations and Anomalous Diffusion

NASA Astrophysics Data System (ADS)

Evangelista, Luiz Roberto; Kaminski Lenzi, Ervin

2018-01-01

Preface; 1. Mathematical preliminaries; 2. A survey of the fractional calculus; 3. From normal to anomalous diffusion; 4. Fractional diffusion equations: elementary applications; 5. Fractional diffusion equations: surface effects; 6. Fractional nonlinear diffusion equation; 7. Anomalous diffusion: anisotropic case; 8. Fractional Schrödinger equations; 9. Anomalous diffusion and impedance spectroscopy; 10. The Poisson–Nernst–Planck anomalous (PNPA) models; References; Index.

A clinical perspective on the 2016 WHO brain tumor classification and routine molecular diagnostics.

PubMed

van den Bent, Martin J; Weller, Michael; Wen, Patrick Y; Kros, Johan M; Aldape, Ken; Chang, Susan

2017-05-01

The 2007 World Health Organization (WHO) classification of brain tumors did not use molecular abnormalities as diagnostic criteria. Studies have shown that genotyping allows a better prognostic classification of diffuse glioma with improved treatment selection. This has resulted in a major revision of the WHO classification, which is now for adult diffuse glioma centered around isocitrate dehydrogenase (IDH) and 1p/19q diagnostics. This revised classification is reviewed with a focus on adult brain tumors, and includes a recommendation of genes of which routine testing is clinically useful. Apart from assessment of IDH mutational status including sequencing of R132H-immunohistochemistry negative cases and testing for 1p/19q, several other markers can be considered for routine testing, including assessment of copy number alterations of chromosome 7 and 10 and of TERT promoter, BRAF, and H3F3A mutations. For "glioblastoma, IDH mutated" the term "astrocytoma grade IV" could be considered. It should be considered to treat IDH wild-type grades II and III diffuse glioma with polysomy of chromosome 7 and loss of 10q as glioblastoma. New developments must be more quickly translated into further revised diagnostic categories. Quality control and rapid integration of molecular findings into the final diagnosis and the communication of the final diagnosis to clinicians require systematic attention. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Adult Central Nervous System Tumors Treatment (PDQ®)—Health Professional Version

Cancer.gov

Most primary brain tumors are astrocytomas, glioblastomas, and meningiomas. Most primary spinal tumors are schwannomas, meningiomas, and ependymomas. Metastatic brain tumors have spread to the brain from other parts of the body. Get detailed information about CNS tumors and treatment in this summary for clinicians.

MGH-USC Human Connectome Project Datasets with Ultra-High b-Value Diffusion MRI

PubMed Central

Fan, Qiuyun; Witzel, Thomas; Nummenmaa, Aapo; Van Dijk, Koene R.A.; Van Horn, John D.; Drews, Michelle K.; Somerville, Leah H.; Sheridan, Margaret A.; Santillana, Rosario M.; Snyder, Jenna; Hedden, Trey; Shaw, Emily E.; Hollinshead, Marisa O.; Renvall, Ville; Zanzonico, Roberta; Keil, Boris; Cauley, Stephen; Polimeni, Jonathan R.; Tisdall, Dylan; Buckner, Randy L.; Wedeen, Van J.; Wald, Lawrence L.; Toga, Arthur W.; Rosen, Bruce R.

2015-01-01

The MGH-USC CONNECTOM MRI scanner housed at the Massachusetts General Hospital (MGH) is a major hardware innovation of the Human Connectome Project (HCP). The 3T CONNECTOM scanner is capable of producing magnetic field gradient of up to 300 mT/m strength for in vivo human brain imaging, which greatly shortens the time spent on diffusion encoding, and decreases the signal loss due to T2 decay. To demonstrate the capability of the novel gradient system, data of healthy adult participants were acquired for this MGH-USC Adult Diffusion Dataset (N=35), minimally preprocessed, and shared through the Laboratory of Neuro Imaging Image Data Archive (LONI IDA) and the WU-Minn Connectome Database (ConnecomeDB). Another purpose of sharing the data is to facilitate methodological studies of diffusion MRI (dMRI) analyses utilizing high diffusion contrast, which perhaps is not easily feasible with standard MR gradient system. In addition, acquisition of the MGH-Harvard-USC Lifespan Dataset is currently underway to include 120 healthy participants ranging from 8 to 90 years old, which will also be shared through LONI IDA and ConnectomeDB. Here we describe the efforts of the MGH-USC HCP consortium in acquiring and sharing the ultra-high b-value diffusion MRI data and provide a report on data preprocessing and access. We conclude with a demonstration of the example data, along with results of standard diffusion analyses, including q-ball Orientation Distribution Function (ODF) reconstruction and tractography. PMID:26364861

Sunitinib Malate in Treating Younger Patients With Recurrent, Refractory, or Progressive Malignant Glioma or Ependymoma

ClinicalTrials.gov

2015-08-18

Childhood Cerebellar Anaplastic Astrocytoma; Childhood Cerebral Anaplastic Astrocytoma; Childhood Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma

Oxaliplatin and Irinotecan in Treating Young Patients With Refractory Solid Tumors or Lymphomas

ClinicalTrials.gov

2013-06-04

Childhood Burkitt Lymphoma; Childhood Central Nervous System Germ Cell Tumor; Childhood Diffuse Large Cell Lymphoma; Childhood Grade III Lymphomatoid Granulomatosis; Childhood Immunoblastic Large Cell Lymphoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Liver Cancer; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Medulloblastoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway Glioma; Recurrent Colon Cancer; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Melanoma; Recurrent Nasopharyngeal Cancer; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Recurrent Wilms Tumor and Other Childhood Kidney Tumors; Recurrent/Refractory Childhood Hodgkin Lymphoma; Unspecified Childhood Solid Tumor, Protocol Specific

Cognitive deficits and predictors 3 years after diagnosis of a pilocytic astrocytoma in childhood.

PubMed

Aarsen, Femke K; Paquier, Philippe F; Arts, Willem-Frans; Van Veelen, Marie-Lise; Michiels, Erna; Lequin, Maarten; Catsman-Berrevoets, Coriene E

2009-07-20

PURPOSE To prospectively study cognitive deficits and predictors 3 years after diagnosis in a large series of pediatric patients treated for pilocytic astrocytoma (PA). PATIENTS AND METHODS Sixty-one of 67 children were grouped according to infratentorial, supratentorial midline, and supratentorial hemispheric site. Intelligence, memory, attention, language, visual-spatial, and executive functions were assessed. Included predictors were sex, age, relapse, diagnosis-assessment interval, hydrocephalus, kind of treatment, and tumor variables. Results All children with PA had problems with sustained attention and speed. In the infratentorial group, there also were deficits in verbal intelligence, visual-spatial memory, executive functioning, and naming. Verbal intelligence and verbal memory problems occurred in the brainstem tumor group. The supratentorial hemispheric tumor group had additional problems with selective attention and executive functioning, and the supratentorial midline tumor group displayed no extra impairments. More specifically, the dorsal supratentorial midline tumor group displayed problems with language and verbal memory. Predictors for lower cognitive functioning were hydrocephalus, radiotherapy, residual tumor size, and age; predictors for better functioning were chemotherapy or treatment of hydrocephalus. Almost 60% of children had problems with academic achievement, for which risk factors were relapse and younger age at diagnosis. CONCLUSION Despite normal intelligence at long-term follow-up, children treated for PA display invalidating cognitive impairments. Adequate treatment of hydrocephalus is important for a more favorable long-term cognitive outcome. Even children without initial severe deficits may develop cognitive impairments years after diagnosis, partly because of the phenomenon of growing into deficit, which has devastating implications for academic achievement and quality of life (QOL).

Automated voxel classification used with atlas-guided diffuse optical tomography for assessment of functional brain networks in young and older adults.

PubMed

Li, Lin; Cazzell, Mary; Babawale, Olajide; Liu, Hanli

2016-10-01

Atlas-guided diffuse optical tomography (atlas-DOT) is a computational means to image changes in cortical hemodynamic signals during human brain activities. Graph theory analysis (GTA) is a network analysis tool commonly used in functional neuroimaging to study brain networks. Atlas-DOT has not been analyzed with GTA to derive large-scale brain connectivity/networks based on near-infrared spectroscopy (NIRS) measurements. We introduced an automated voxel classification (AVC) method that facilitated the use of GTA with atlas-DOT images by grouping unequal-sized finite element voxels into anatomically meaningful regions of interest within the human brain. The overall approach included volume segmentation, AVC, and cross-correlation. To demonstrate the usefulness of AVC, we applied reproducibility analysis to resting-state functional connectivity measurements conducted from 15 young adults in a two-week period. We also quantified and compared changes in several brain network metrics between young and older adults, which were in agreement with those reported by a previous positron emission tomography study. Overall, this study demonstrated that AVC is a useful means for facilitating integration or combination of atlas-DOT with GTA and thus for quantifying NIRS-based, voxel-wise resting-state functional brain networks.

The 2016 revision of the WHO Classification of Central Nervous System Tumours: retrospective application to a cohort of diffuse gliomas.

PubMed

Rogers, Te Whiti; Toor, Gurvinder; Drummond, Katharine; Love, Craig; Field, Kathryn; Asher, Rebecca; Tsui, Alpha; Buckland, Michael; Gonzales, Michael

2018-03-01

The classification of central nervous system tumours has more recently been shaped by a focus on molecular pathology rather than histopathology. We re-classified 82 glial tumours according to the molecular-genetic criteria of the 2016 revision of the World Health Organization (WHO) Classification of Tumours of the Central Nervous System. Initial diagnoses and grading were based on the morphological criteria of the 2007 WHO scheme. Because of the impression of an oligodendroglial component on initial histological assessment, each tumour was tested for co-deletion of chromosomes 1p and 19q and mutations of isocitrate dehydrogenase (IDH-1 and 2) genes. Additionally, expression of proteins encoded by alpha-thalassemia X-linked mental retardation (ATRX) and TP53 genes was assessed by immunohistochemistry. We found that all but two tumours could be assigned to a specific category in the 2016 revision. The most common change in diagnosis was from oligoastrocytoma to specifically astrocytoma or oligodendroglioma. Analysis of progression free survival (PFS) for WHO grade II and III tumours showed that the objective criteria of the 2016 revision separated diffuse gliomas into three distinct molecular categories: chromosome 1p/19q co-deleted/IDH mutant, intact 1p/19q/IDH mutant and IDH wild type. No significant difference in PFS was found when comparing IDH mutant grade II and III tumours suggesting that IDH status is more informative than tumour grade. The segregation into distinct molecular sub-types that is achieved by the 2016 revision provides an objective evidence base for managing patients with grade II and III diffuse gliomas based on prognosis.

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

PubMed Central

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

2017-01-01

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

MGH-USC Human Connectome Project datasets with ultra-high b-value diffusion MRI.

PubMed

Fan, Qiuyun; Witzel, Thomas; Nummenmaa, Aapo; Van Dijk, Koene R A; Van Horn, John D; Drews, Michelle K; Somerville, Leah H; Sheridan, Margaret A; Santillana, Rosario M; Snyder, Jenna; Hedden, Trey; Shaw, Emily E; Hollinshead, Marisa O; Renvall, Ville; Zanzonico, Roberta; Keil, Boris; Cauley, Stephen; Polimeni, Jonathan R; Tisdall, Dylan; Buckner, Randy L; Wedeen, Van J; Wald, Lawrence L; Toga, Arthur W; Rosen, Bruce R

2016-01-01

The MGH-USC CONNECTOM MRI scanner housed at the Massachusetts General Hospital (MGH) is a major hardware innovation of the Human Connectome Project (HCP). The 3T CONNECTOM scanner is capable of producing a magnetic field gradient of up to 300 mT/m strength for in vivo human brain imaging, which greatly shortens the time spent on diffusion encoding, and decreases the signal loss due to T2 decay. To demonstrate the capability of the novel gradient system, data of healthy adult participants were acquired for this MGH-USC Adult Diffusion Dataset (N=35), minimally preprocessed, and shared through the Laboratory of Neuro Imaging Image Data Archive (LONI IDA) and the WU-Minn Connectome Database (ConnectomeDB). Another purpose of sharing the data is to facilitate methodological studies of diffusion MRI (dMRI) analyses utilizing high diffusion contrast, which perhaps is not easily feasible with standard MR gradient system. In addition, acquisition of the MGH-Harvard-USC Lifespan Dataset is currently underway to include 120 healthy participants ranging from 8 to 90 years old, which will also be shared through LONI IDA and ConnectomeDB. Here we describe the efforts of the MGH-USC HCP consortium in acquiring and sharing the ultra-high b-value diffusion MRI data and provide a report on data preprocessing and access. We conclude with a demonstration of the example data, along with results of standard diffusion analyses, including q-ball Orientation Distribution Function (ODF) reconstruction and tractography. Copyright © 2015 Elsevier Inc. All rights reserved.

Diffusion archeology for diffusion progression history reconstruction.

PubMed

Sefer, Emre; Kingsford, Carl

2016-11-01

Diffusion through graphs can be used to model many real-world processes, such as the spread of diseases, social network memes, computer viruses, or water contaminants. Often, a real-world diffusion cannot be directly observed while it is occurring - perhaps it is not noticed until some time has passed, continuous monitoring is too costly, or privacy concerns limit data access. This leads to the need to reconstruct how the present state of the diffusion came to be from partial diffusion data. Here, we tackle the problem of reconstructing a diffusion history from one or more snapshots of the diffusion state. This ability can be invaluable to learn when certain computer nodes are infected or which people are the initial disease spreaders to control future diffusions. We formulate this problem over discrete-time SEIRS-type diffusion models in terms of maximum likelihood. We design methods that are based on submodularity and a novel prize-collecting dominating-set vertex cover (PCDSVC) relaxation that can identify likely diffusion steps with some provable performance guarantees. Our methods are the first to be able to reconstruct complete diffusion histories accurately in real and simulated situations. As a special case, they can also identify the initial spreaders better than the existing methods for that problem. Our results for both meme and contaminant diffusion show that the partial diffusion data problem can be overcome with proper modeling and methods, and that hidden temporal characteristics of diffusion can be predicted from limited data.

High-energy phosphate transfer in human muscle: diffusion of phosphocreatine.

PubMed

Gabr, Refaat E; El-Sharkawy, Abdel-Monem M; Schär, Michael; Weiss, Robert G; Bottomley, Paul A

2011-07-01

The creatine kinase (CK) reaction is central to muscle energetics, buffering ATP levels during periods of intense activity via consumption of phosphocreatine (PCr). PCr is believed to serve as a spatial shuttle of high-energy phosphate between sites of energy production in the mitochondria and sites of energy utilization in the myofibrils via diffusion. Knowledge of the diffusion coefficient of PCr (D(PCr)) is thus critical for modeling and understanding energy transport in the myocyte, but D(PCr) has not been measured in humans. Using localized phosphorus magnetic resonance spectroscopy, we measured D(PCr) in the calf muscle of 11 adults as a function of direction and diffusion time. The results show that the diffusion of PCr is anisotropic, with significantly higher diffusion along the muscle fibers, and that the diffusion of PCr is restricted to a ∼28-μm pathlength assuming a cylindrical model, with an unbounded diffusion coefficient of ∼0.69 × 10(-3) mm(2)/s. This distance is comparable in size to the myofiber radius. On the basis of prior measures of CK reaction kinetics in human muscle, the expected diffusion distance of PCr during its half-life in the CK reaction is ∼66 μm. This distance is much greater than the average distances between mitochondria and myofibrils. Thus these first measurements of PCr diffusion in human muscle in vivo support the view that PCr diffusion is not a factor limiting high-energy phosphate transport between the mitochondria and the myofibrils in healthy resting myocytes.

High-energy phosphate transfer in human muscle: diffusion of phosphocreatine

PubMed Central

Gabr, Refaat E.; El-Sharkawy, AbdEl-Monem M.; Schär, Michael; Weiss, Robert G.

2011-01-01

The creatine kinase (CK) reaction is central to muscle energetics, buffering ATP levels during periods of intense activity via consumption of phosphocreatine (PCr). PCr is believed to serve as a spatial shuttle of high-energy phosphate between sites of energy production in the mitochondria and sites of energy utilization in the myofibrils via diffusion. Knowledge of the diffusion coefficient of PCr (DPCr) is thus critical for modeling and understanding energy transport in the myocyte, but DPCr has not been measured in humans. Using localized phosphorus magnetic resonance spectroscopy, we measured DPCr in the calf muscle of 11 adults as a function of direction and diffusion time. The results show that the diffusion of PCr is anisotropic, with significantly higher diffusion along the muscle fibers, and that the diffusion of PCr is restricted to a ∼28-μm pathlength assuming a cylindrical model, with an unbounded diffusion coefficient of ∼0.69 × 10−3 mm2/s. This distance is comparable in size to the myofiber radius. On the basis of prior measures of CK reaction kinetics in human muscle, the expected diffusion distance of PCr during its half-life in the CK reaction is ∼66 μm. This distance is much greater than the average distances between mitochondria and myofibrils. Thus these first measurements of PCr diffusion in human muscle in vivo support the view that PCr diffusion is not a factor limiting high-energy phosphate transport between the mitochondria and the myofibrils in healthy resting myocytes. PMID:21368292

Complete diagnostics and clinical approach for a female patient with unusual glioblastoma: A case study.

PubMed

Samal, Filip; Stanek, Libor; Filip, Michal; Haninec, Pavel; Vícha, Ales; Musil, Zdenek; Tesarova, Petra; Petruzelka, Lubos; Springer, Drahomira; Kralickova, Milena; Kohoutova, Milada; Zima, Tomas

2016-07-01

The present study reports a case of a 44-year-old female patient with a large frontal lobe tumor who underwent surgery using a modern navigation system SonoWand that combines the advantages of a non-frame navigation system with intraoperative real-time ultrasound imaging. The right frontal lobe tumor consisted of two morphologically different sections. A diffuse astrocytoma grade II and a glioblastoma grade IV were identified. These tumors were relatively substantially separated. A 17 p deletion, including TP53 , was detected in a diffuse astrocytoma but not in a glioblastoma. EGFR and MDM2 amplifications were detected only in a glioblastoma. Detection of these amplifications is typical for primary glioblastomas. These findings support our assumption of two independent tumors. The KRAS , BRAF and EGFR gene mutations were also detected in a glioblastoma. Such an accumulation of molecular mutations is rare in one tumor. Following oncological treatment the patient was cared for in the oncological center and survived for 15 months after the surgery without any signs of a disease. This is an unusual case, and to the best of our knowledge, is not frequently published in literature.

Diffusing diffusivity: Rotational diffusion in two and three dimensions

NASA Astrophysics Data System (ADS)

Jain, Rohit; Sebastian, K. L.

2017-06-01

We consider the problem of calculating the probability distribution function (pdf) of angular displacement for rotational diffusion in a crowded, rearranging medium. We use the diffusing diffusivity model and following our previous work on translational diffusion [R. Jain and K. L. Sebastian, J. Phys. Chem. B 120, 3988 (2016)], we show that the problem can be reduced to that of calculating the survival probability of a particle undergoing Brownian motion, in the presence of a sink. We use the approach to calculate the pdf for the rotational motion in two and three dimensions. We also propose new dimensionless, time dependent parameters, αr o t ,2 D and αr o t ,3 D, which can be used to analyze the experimental/simulation data to find the extent of deviation from the normal behavior, i.e., constant diffusivity, and obtain explicit analytical expressions for them, within our model.

Diffusion archeology for diffusion progression history reconstruction

PubMed Central

Sefer, Emre; Kingsford, Carl

2015-01-01

Diffusion through graphs can be used to model many real-world processes, such as the spread of diseases, social network memes, computer viruses, or water contaminants. Often, a real-world diffusion cannot be directly observed while it is occurring — perhaps it is not noticed until some time has passed, continuous monitoring is too costly, or privacy concerns limit data access. This leads to the need to reconstruct how the present state of the diffusion came to be from partial diffusion data. Here, we tackle the problem of reconstructing a diffusion history from one or more snapshots of the diffusion state. This ability can be invaluable to learn when certain computer nodes are infected or which people are the initial disease spreaders to control future diffusions. We formulate this problem over discrete-time SEIRS-type diffusion models in terms of maximum likelihood. We design methods that are based on submodularity and a novel prize-collecting dominating-set vertex cover (PCDSVC) relaxation that can identify likely diffusion steps with some provable performance guarantees. Our methods are the first to be able to reconstruct complete diffusion histories accurately in real and simulated situations. As a special case, they can also identify the initial spreaders better than the existing methods for that problem. Our results for both meme and contaminant diffusion show that the partial diffusion data problem can be overcome with proper modeling and methods, and that hidden temporal characteristics of diffusion can be predicted from limited data. PMID:27821901

Directional diffusivity as a magnetic resonance (MR) biomarker in demyelinating disease

NASA Astrophysics Data System (ADS)

Benzinger, Tammie L. S.; Cross, Anne H.; Xu, Junqian; Naismith, Robert; Sun, Shu-Wei; Song, Sheng-Kwei

2007-09-01

Directional diffusivities derived from diffusion tensor magnetic resonance imaging (DTI) measurements describe water movement parallel to (λ ||, axial diffusivity) and perpendicular to (λ⊥radial diffusivity) axonal tracts. λ || and λ⊥ have been shown to differentially detect axon and myelin abnormalities in several mouse models of central nervous system white matter pathology in our laboratory. These models include experimental autoimmune encephalomyelitis (EAE), (1) myelin basic protein mutant mice with dysmyelination and intact axons, (2) cuprizone-induced demyelination, and remyelination, with reversible axon injury (2, 3) and a model of retinal ischemia in which retinal ganglion cell death is followed by Wallerian degeneration of optic nerve, with axonal injury preceding demyelination. (4) Decreased λ|| correlates with acute axonal injury and increased λ⊥ indicates myelin damage. (4) More recently, we have translated this approach to human MR, investigating acute and chronic optic neuritis in adults with multiple sclerosis, brain lesions in adults with multiple sclerosis, and acute disseminated encephalomyelitis (ADEM) in children. We are also investigating the use of this technique to probe the underlying structural change of the cervical spinal cord in acute and chronic T2- hyperintense lesions in spinal stenosis, trauma, and transverse myelitis. In each of these demyelinating diseases, the discrimination between axonal and myelin injury which we can achieve has important prognostic and therapeutic implications. For those patients with myelin injury but intact axons, early, directed drug therapy has the potential to prevent progression to axonal loss and permanent disability.

Effects of different cooling treatments on water diffusion, microcirculation, and water content within exercised muscles: evaluation by magnetic resonance T2-weighted and diffusion-weighted imaging.

PubMed

Yanagisawa, Osamu; Takahashi, Hideyuki; Fukubayashi, Toru

2010-09-01

In this study, we determined the effects of different cooling treatments on exercised muscles. Seven adults underwent four post-exercise treatments (20-min ice-bag application, 60-min gel-pack application at 10 degrees C and 17 degrees C, and non-cooling treatment) with at least 1 week between treatments. Magnetic resonance diffusion- and T2-weighted images were obtained to calculate the apparent diffusion coefficients (apparent diffusion coefficient 1, which reflects intramuscular water diffusion and microcirculation, and apparent diffusion coefficient 2, which is approximately equal to the true diffusion coefficient that excludes as much of the effect of intramuscular microcirculation as possible) and the T2 values (intramuscular water content level) of the ankle dorsiflexors, respectively, before and after ankle dorsiflexion exercise and after post-exercise treatment. The T2 values increased significantly after exercise and returned to pre-exercise values after each treatment; no significant differences were observed among the four post-exercise treatments. Both apparent diffusion coefficients also increased significantly after exercise and decreased significantly after the three cooling treatments; no significant difference was detected among the three cooling treatments. Local cooling suppresses both water diffusion and microcirculation within exercised muscles. Moreover, although the treatment time was longer, adequate cooling effects could be achieved using the gel-pack applications at relatively mild cooling temperatures.

Intracellular diffusion restrictions in isolated cardiomyocytes from rainbow trout.

PubMed

Sokolova, Niina; Vendelin, Marko; Birkedal, Rikke

2009-12-17

Restriction of intracellular diffusion of adenine nucleotides has been studied intensively on adult rat cardiomyocytes. However, their cause and role in vivo is still uncertain. Intracellular membrane structures have been suggested to play a role. We therefore chose to study cardiomyocytes from rainbow trout (Oncorhynchus mykiss), which are thinner and have fewer intracellular membrane structures than adult rat cardiomyocytes. Previous studies suggest that trout permeabilized cardiac fibers also have diffusion restrictions. However, results from fibers may be affected by incomplete separation of the cells. This is avoided when studying permeabilized, isolated cardiomyocytes. The aim of this study was to verify the existence of diffusion restrictions in trout cardiomyocytes by comparing ADP-kinetics of mitochondrial respiration in permeabilized fibers, permeabilized cardiomyocytes and isolated mitochondria from rainbow trout heart. Experiments were performed at 10, 15 and 20 degrees C in the absence and presence of creatine. Trout cardiomyocytes hypercontracted in the solutions used for mammalian cardiomyocytes. We developed a new solution in which they retained their shape and showed stable steady state respiration rates throughout an experiment. The apparent ADP-affinity of permeabilized cardiomyocytes was different from that of fibers. It was higher, independent of temperature and not increased by creatine. However, it was still about ten times lower than in isolated mitochondria. The differences between fibers and cardiomyocytes suggest that results from trout heart fibers were affected by incomplete separation of the cells. However, the lower ADP-affinity of cardiomyocytes compared to isolated mitochondria indicate that intracellular diffusion restrictions are still present in trout cardiomyocytes despite their lower density of intracellular membrane structures. The lack of a creatine effect indicates that trout heart lacks mitochondrial creatine kinase tightly

Adopting NDN Projects. A Guide for Adult Education Programs.

ERIC Educational Resources Information Center

Office of Vocational and Adult Education (ED), Washington, DC.

This guide is designed to assist adult education leaders and practitioners to consider carefully the adoption of one or more of the available National Diffusion Network (NDN) projects. It is also intended to help them understand their opportunity and responsibility for improving adult education practice through the proper use of adoption…

Multispecies diffusion models: A study of uranyl species diffusion

NASA Astrophysics Data System (ADS)

Liu, Chongxuan; Shang, Jianying; Zachara, John M.

2011-12-01

Rigorous numerical description of multispecies diffusion requires coupling of species, charge, and aqueous and surface complexation reactions that collectively affect diffusive fluxes. The applicability of a fully coupled diffusion model is, however, often constrained by the availability of species self-diffusion coefficients, as well as by computational complication in imposing charge conservation. In this study, several diffusion models with variable complexity in charge and species coupling were formulated and compared to describe reactive multispecies diffusion in groundwater. Diffusion of uranyl [U(VI)] species was used as an example in demonstrating the effectiveness of the models in describing multispecies diffusion. Numerical simulations found that a diffusion model with a single, common diffusion coefficient for all species was sufficient to describe multispecies U(VI) diffusion under a steady state condition of major chemical composition, but not under transient chemical conditions. Simulations revealed that for multispecies U(VI) diffusion under transient chemical conditions, a fully coupled diffusion model could be well approximated by a component-based diffusion model when the diffusion coefficient for each chemical component was properly selected. The component-based diffusion model considers the difference in diffusion coefficients between chemical components, but not between the species within each chemical component. This treatment significantly enhanced computational efficiency at the expense of minor charge conservation. The charge balance in the component-based diffusion model can be enforced, if necessary, by adding a secondary migration term resulting from model simplification. The effect of ion activity coefficient gradients on multispecies diffusion is also discussed. The diffusion models were applied to describe U(VI) diffusive mass transfer in intragranular domains in two sediments collected from U.S. Department of Energy's Hanford 300A

Reduced white matter integrity and verbal fluency impairment in young adults with bipolar disorder: a diffusion tensor imaging study

PubMed Central

Bauer, Isabelle E.; Ouyang, Austin; Mwangi, Benson; Sanches, Marsal; Zunta-Soares, Giovana B.; Keefe, Richard S. E.; Huang, Hao; Soares, Jair C.

2015-01-01

Background Clinical evidence shows that bipolar disorder (BD) is characterized by white matter (WM) microstructural abnormalities. However, little is known about the biological mechanisms associated with these abnormalities and their relationship with cognitive functioning. Methods 49 adult BD patients ((M±SD): 29.27 ± 7.92 years; 17 males, 32 females; 34 BD-I, 10 BD-II, and 5 BD-NOS) and 28 age-matched normal subjects ((M±SD): 29.19 ± 7.35 years; 10 males and 18 females) underwent diffusion tensor imaging (DTI) imaging. DTI metrics were computed using whole-brain tract-based spatial statistics (TBSS) as part of the FMRIB Software Library. Measures of WM coherence (fractional anisotropy - FA) and axonal structure (mean, axial and radial diffusivity - MD, AD and RD) were employed to characterize the microstructural alterations in the limbic, commissural, association and projection fiber tracts. All participants performed the Brief Assessment of Cognition for Affective disorders (BAC-A). Results BD patients performed poorly on verbal fluency tasks and exhibited large clusters of altered FA, RD and MD values within the retrolenticular part of the internal capsule, the superior and anterior corona radiata, and the corpus callosum. Increased FA values in the left IFOF and the forceps minor correlated positively with verbal fluency scores. Altered RD parameters in the corticospinal tract and the forceps minor were associated with reduced visuomotor abilities. Conclusions The reported verbal fluency deficits and FA, RD and MD alterations in WM structures are potential cognitive and neural markers of BD. Abnormal RD values may be associated with progressive demyelination. PMID:25684152

Evaluation of amentoflavone isolated from Cnestis ferruginea Vahl ex DC (Connaraceae) on production of inflammatory mediators in LPS stimulated rat astrocytoma cell line (C6) and THP-1 cells.

PubMed

Ishola, I O; Chaturvedi, J P; Rai, S; Rajasekar, N; Adeyemi, O O; Shukla, R; Narender, T

2013-03-27

Cnestisferruginea (CF) Vahl ex DC (Connaraceae) is a shrub widely used in traditional African medicine for the treatment of various psychiatric illness and inflammatory conditions. This study was carried out to investigate the effect of amentoflavone isolated from methanolic root extract of CF on lipopolysaccharide (LPS)-induced neuroinflammatory cascade of events associated to the oxidative and nitrative stress, and TNF-α production in rat astrocytoma cell line (C6) and human monocytic leukemia cell line (THP-1), respectively. Rat astrocytoma cells (C6) were stimulated with LPS (10μg/ml) alone and in the presence of different concentrations of amentoflavone (0.1-3μg/ml) for 24h incubation period. Nitrite release, reactive oxygen species (ROS), malondialdehyde (MDA) and reduced-glutathione (GSH) in C6 cells were estimated; while the TNF-α level was estimated in THP-1 cell lysate. In vivo analgesic activity was evaluated using mouse writhing and hot plate tests while the anti-inflammatory effect was investigated using carrageenan-induced oedema test. LPS (10μg/ml) significantly (P<0.05) stimulated C6 cells to release nitrite, ROS, MDA, and TNF-α generation while GSH was down regulated in comparison to control. However, amentoflavone significantly (P<0.05) attenuated nitrite, ROS, MDA and TNF-α generation and also up regulated the level of GSH. Amentoflavone per se did not have any significant effect on C6 and THP-1 cells. Amentoflavone (6.25-50mg/kg) significantly (P<0.05) reduced number of writhes and also increase pain threshold in hot plate test. It produced time course significant (P<0.05) decrease in oedema formation in rodents. Findings in this study demonstrate the anti-neuroinflammatory and antinoceptive effects of amentoflavone which may suggest its beneficial roles in neuroinflammation associated disorders. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Pressure transfer function and absorption cross section from the diffuse field to the human infant ear canal.

PubMed

Keefe, D H; Bulen, J C; Campbell, S L; Burns, E M

1994-01-01

The diffuse-field pressure transfer function from a reverberant field to the ear canal of human infants, ages 1, 3, 6, 12, and 24 months, has been measured from 125-10700 Hz. The source was a loudspeaker using pink noise, and the diffuse-field pressure and the ear-canal pressure were simultaneously measured using a spatial averaging technique in a reverberant room. The results in most subjects show a two-peak structure in the 2-6-kHz range, corresponding to the ear-canal and concha resonances. The ear-canal resonance frequency decreases from 4.4 kHz at age 1 month to 2.9 kHz at age 24 months. The concha resonance frequency decreases from 5.5 kHz at age 1 month to 4.5 kHz at age 24 months. Below 2 kHz, the diffuse-field transfer function shows effects due to the torsos of the infant and parent, and varies with how the infant is held. Comparisons are reported of the diffuse-field absorption cross section for infants relative to adults. This quantity is a measure of power absorbed by the middle ear from a diffuse sound field, and large differences are observed in infants relative to adults. The radiation efficiencies of the infant and the adult ear are small at low frequencies, near unity at midfrequencies, and decrease at higher frequencies. The process of ear-canal development is not yet complete at age 24 months. The results have implications for experiments on hearing in infants.

Primary renal diffuse large B-cell lymphoma with central nervous system involvement: a rare case report and literature review.

PubMed

Wang, Ying; Guo, Shuangshuang

2015-01-01

Primary renal lymphoma is a rare entity. Of these, diffuse large B-cell lymphoma is the most common pathological type and, R-CHOP regimen was the preferred chemotherapy for it. Here we present an adult case of primary renal diffuse large B-cell lymphoma.

huJCAR014 CAR-T Cells in Treating Adult Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma or Acute Lymphoblastic Leukemia

ClinicalTrials.gov

2018-05-25

Adult B Acute Lymphoblastic Leukemia; BCL2 Gene Rearrangement; BCL6 Gene Rearrangement; CD19 Positive; Diffuse Large B-Cell Lymphoma, Not Otherwise Specified; MYC Gene Rearrangement; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Refractory Adult Acute Lymphoblastic Leukemia; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Transformed Recurrent Non-Hodgkin Lymphoma

Multi-compartment microscopic diffusion imaging

PubMed Central

Kaden, Enrico; Kelm, Nathaniel D.; Carson, Robert P.; Does, Mark D.; Alexander, Daniel C.

2017-01-01

This paper introduces a multi-compartment model for microscopic diffusion anisotropy imaging. The aim is to estimate microscopic features specific to the intra- and extra-neurite compartments in nervous tissue unconfounded by the effects of fibre crossings and orientation dispersion, which are ubiquitous in the brain. The proposed MRI method is based on the Spherical Mean Technique (SMT), which factors out the neurite orientation distribution and thus provides direct estimates of the microscopic tissue structure. This technique can be immediately used in the clinic for the assessment of various neurological conditions, as it requires only a widely available off-the-shelf sequence with two b-shells and high-angular gradient resolution achievable within clinically feasible scan times. To demonstrate the developed method, we use high-quality diffusion data acquired with a bespoke scanner system from the Human Connectome Project. This study establishes the normative values of the new biomarkers for a large cohort of healthy young adults, which may then support clinical diagnostics in patients. Moreover, we show that the microscopic diffusion indices offer direct sensitivity to pathological tissue alterations, exemplified in a preclinical animal model of Tuberous Sclerosis Complex (TSC), a genetic multi-organ disorder which impacts brain microstructure and hence may lead to neurological manifestations such as autism, epilepsy and developmental delay. PMID:27282476

Dorsally exophytic glioblastoma arising from the medulla oblongata in an adult presenting as 4th ventricular mass.

PubMed

Das, Kuntal Kanti; Bettaswamy, Guru Prasad; Mehrotra, Anant; Jaiswal, Sushila; Jaiswal, Awadhesh Kumar; Behari, Sanjay

2017-01-01

Brainstem gliomas are relatively rare in adults (<2% of all gliomas). Exophytic gliomas are focal brainstem lesions, which project into the 4 th ventricle or cerebellopontine angles. These exophytic lesions are usually of low-grade histology (pilocytic astrocytoma or ganglioglioma) and have a relatively better outcome compared with brainstem gliomas as a whole. Glioblastoma is the commonest primary glial cell neoplasm and mostly occurs in the supratentorial compartment. It is rather uncommon in the brainstem and seldom has been described as having an exophytic growth pattern. Here we describe an exophytic brainstem glioblastoma arising from the medulla oblongata in a 55-year-old lady who presented with a 4 th ventricular mass, and present a brief review of the literature. Till now, six cases of glioblastoma arising from the medulla oblongata have been reported. So, ours is the seventh such report. To the best of our knowledge, it also happens to be the sixth reported case of dorsally exophytic brainstem glioblastoma till date.

Diffusion tensor imaging reveals changes in the adult rat brain following long-term and passive moderate acoustic exposure.

PubMed

Abdoli, Sherwin; Ho, Leon C; Zhang, Jevin W; Dong, Celia M; Lau, Condon; Wu, Ed X

2016-12-01

This study investigated neuroanatomical changes following long-term acoustic exposure at moderate sound pressure level (SPL) under passive conditions, without coupled behavioral training. The authors utilized diffusion tensor imaging (DTI) to detect morphological changes in white matter. DTIs from adult rats (n = 8) exposed to continuous acoustic exposure at moderate SPL for 2 months were compared with DTIs from rats (n = 8) reared under standard acoustic conditions. Two distinct forms of DTI analysis were applied in a sequential manner. First, DTI images were analyzed using voxel-based statistics which revealed greater fractional anisotropy (FA) of the pyramidal tract and decreased FA of the tectospinal tract and trigeminothalamic tract of the exposed rats. Region of interest analysis confirmed (p < 0.05) that FA had increased in the pyramidal tract but did not show a statistically significant difference in the FA of the tectospinal or trigeminothalamic tract. The results of the authors show that long-term and passive acoustic exposure at moderate SPL increases the organization of white matter in the pyramidal tract.

MRI correlates of general intelligence in neurotypical adults.

PubMed

Malpas, Charles B; Genc, Sila; Saling, Michael M; Velakoulis, Dennis; Desmond, Patricia M; O'Brien, Terence J

2016-02-01

There is growing interest in the neurobiological substrate of general intelligence. Psychometric estimates of general intelligence are reduced in a range of neurological disorders, leading to practical application as sensitive, but non-specific, markers of cerebral disorder. This study examined estimates of general intelligence in neurotypical adults using diffusion tensor imaging and resting-state functional connectivity analysis. General intelligence was related to white matter organisation across multiple brain regions, confirming previous work in older healthy adults. We also found that variation in general intelligence was related to a large functional sub-network involving all cortical lobes of the brain. These findings confirm that individual variance in general intelligence is related to diffusely represented brain networks. Copyright © 2015 Elsevier Ltd. All rights reserved.

Serial MR diffusion to predict treatment response in high-grade pediatric brain tumors: a comparison of regional and voxel-based diffusion change metrics

PubMed Central

Rodriguez Gutierrez, Daniel; Manita, Muftah; Jaspan, Tim; Dineen, Robert A.; Grundy, Richard G.; Auer, Dorothee P.

2013-01-01

Background Assessment of treatment response by measuring tumor size is known to be a late and potentially confounded response index. Serial diffusion MRI has shown potential for allowing earlier and possibly more reliable response assessment in adult patients, with limited experience in clinical settings and in pediatric brain cancer. We present a retrospective study of clinical MRI data in children with high-grade brain tumors to assess and compare the values of several diffusion change metrics to predict treatment response. Methods Eighteen patients (age range, 1.9–20.6 years) with high-grade brain tumors and serial diffusion MRI (pre- and posttreatment interval range, 1–16 weeks posttreatment) were identified after obtaining parental consent. The following diffusion change metrics were compared with the clinical response status assessed at 6 months: (1) regional change in absolute and normalized apparent diffusivity coefficient (ADC), (2) voxel-based fractional volume of increased (fiADC) and decreased ADC (fdADC), and (3) a new metric based on the slope of the first principal component of functional diffusion maps (fDM). Results Responders (n = 12) differed significantly from nonresponders (n = 6) in all 3 diffusional change metrics demonstrating higher regional ADC increase, larger fiADC, and steeper slopes (P < .05). The slope method allowed the best response prediction (P < .01, η2 = 0.78) with a classification accuracy of 83% for a slope of 58° using receiver operating characteristic (ROC) analysis. Conclusions We demonstrate that diffusion change metrics are suitable response predictors for high-grade pediatric tumors, even in the presence of variable clinical diffusion imaging protocols. PMID:23585630

Vorinostat, Temozolomide, or Bevacizumab in Combination With Radiation Therapy Followed by Bevacizumab and Temozolomide in Young Patients With Newly Diagnosed High-Grade Glioma

ClinicalTrials.gov

2017-10-11

Brain Stem Glioma; Cerebral Astrocytoma; Childhood Cerebellar Anaplastic Astrocytoma; Childhood Cerebral Anaplastic Astrocytoma; Childhood Spinal Cord Neoplasm; Untreated Childhood Brain Stem Glioma; Untreated Childhood Cerebral Astrocytoma

Spin-diffusions and diffusive molecular dynamics

NASA Astrophysics Data System (ADS)

Farmer, Brittan; Luskin, Mitchell; Plecháč, Petr; Simpson, Gideon

2017-12-01

Metastable configurations in condensed matter typically fluctuate about local energy minima at the femtosecond time scale before transitioning between local minima after nanoseconds or microseconds. This vast scale separation limits the applicability of classical molecular dynamics (MD) methods and has spurned the development of a host of approximate algorithms. One recently proposed method is diffusive MD which aims at integrating a system of ordinary differential equations describing the likelihood of occupancy by one of two species, in the case of a binary alloy, while quasistatically evolving the locations of the atoms. While diffusive MD has shown itself to be efficient and provide agreement with observations, it is fundamentally a model, with unclear connections to classical MD. In this work, we formulate a spin-diffusion stochastic process and show how it can be connected to diffusive MD. The spin-diffusion model couples a classical overdamped Langevin equation to a kinetic Monte Carlo model for exchange amongst the species of a binary alloy. Under suitable assumptions and approximations, spin-diffusion can be shown to lead to diffusive MD type models. The key assumptions and approximations include a well-defined time scale separation, a choice of spin-exchange rates, a low temperature approximation, and a mean field type approximation. We derive several models from different assumptions and show their relationship to diffusive MD. Differences and similarities amongst the models are explored in a simple test problem.

Frontal networks in adults with autism spectrum disorder

PubMed Central

Catani, Marco; Dell’Acqua, Flavio; Budisavljevic, Sanja; Howells, Henrietta; Thiebaut de Schotten, Michel; Froudist-Walsh, Seán; D’Anna, Lucio; Thompson, Abigail; Sandrone, Stefano; Bullmore, Edward T.; Suckling, John; Baron-Cohen, Simon; Lombardo, Michael V.; Wheelwright, Sally J.; Chakrabarti, Bhismadev; Lai, Meng-Chuan; Ruigrok, Amber N. V.; Leemans, Alexander; Ecker, Christine; Consortium, MRC AIMS; Craig, Michael C.

2016-01-01

Abstract It has been postulated that autism spectrum disorder is underpinned by an ‘atypical connectivity’ involving higher-order association brain regions. To test this hypothesis in a large cohort of adults with autism spectrum disorder we compared the white matter networks of 61 adult males with autism spectrum disorder and 61 neurotypical controls, using two complementary approaches to diffusion tensor magnetic resonance imaging. First, we applied tract-based spatial statistics, a ‘whole brain’ non-hypothesis driven method, to identify differences in white matter networks in adults with autism spectrum disorder. Following this we used a tract-specific analysis, based on tractography, to carry out a more detailed analysis of individual tracts identified by tract-based spatial statistics. Finally, within the autism spectrum disorder group, we studied the relationship between diffusion measures and autistic symptom severity. Tract-based spatial statistics revealed that autism spectrum disorder was associated with significantly reduced fractional anisotropy in regions that included frontal lobe pathways. Tractography analysis of these specific pathways showed increased mean and perpendicular diffusivity, and reduced number of streamlines in the anterior and long segments of the arcuate fasciculus, cingulum and uncinate—predominantly in the left hemisphere. Abnormalities were also evident in the anterior portions of the corpus callosum connecting left and right frontal lobes. The degree of microstructural alteration of the arcuate and uncinate fasciculi was associated with severity of symptoms in language and social reciprocity in childhood. Our results indicated that autism spectrum disorder is a developmental condition associated with abnormal connectivity of the frontal lobes. Furthermore our findings showed that male adults with autism spectrum disorder have regional differences in brain anatomy, which correlate with specific aspects of autistic

A Study of the Treatment of Recurrent Malignant Glioma With rQNestin34.5v.2

ClinicalTrials.gov

2018-04-09

Malignant Glioma of Brain; Astrocytoma; Malignant Astrocytoma; Oligodendroglioma; Anaplastic Oligodendroglioma of Brain (Diagnosis); Mixed Oligo-Astrocytoma; Ependymoma; Ganglioglioma; Pylocytic/Pylomyxoid Astrocytoma; Brain Tumor; Glioma; Brain Cancer; Glioblastoma; Glioblastoma Multiforme

Temozolomide and O6-Benzylguanine in Treating Children With Recurrent Brain Tumors

ClinicalTrials.gov

2013-09-27

Childhood Central Nervous System Germ Cell Tumor; 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 Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

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

PubMed

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

2017-03-01

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

Chronology of Milestones for Libraries and Adult Lifelong Learning and Literacy.

ERIC Educational Resources Information Center

McCook, Kathleen de la Pena; Barber, Peggy

This chronology highlights milestones for libraries and adult lifelong learning and literacy from 1924-2001, including the following events: William S. Learned's "The American Public Library and the Diffusion of Knowledge" is published (1924); establishment of the ALA (American Library Association) Adult Education Section (1946); the…

Evaluating the apparent diffusion coefficient in MRI studies as a means of determining paediatric brain tumour stages.

PubMed

Domínguez-Pinilla, N; Martínez de Aragón, A; Diéguez Tapias, S; Toldos, O; Hinojosa Bernal, J; Rigal Andrés, M; González-Granado, L I

2016-09-01

The apparent diffusion coefficient (ADC) in MRI seems to be related to cellularity in brain tumours. Its utility as a tool for distinguishing between histological types and tumour stages remains controversial. We retrospectively evaluated children diagnosed with CNS tumours between January 2008 and December 2013. Data collected were age, sex, histological diagnosis, and location of the tumour. We evaluated the ADC and ADC ratio and correlated those values with histological diagnoses. The study included 55 patients with a median age of 6 years. Histological diagnoses were pilocytic astrocytoma (40%), anaplastic ependymoma (16.4%), ganglioglioma (10.9%), glioblastoma (7.3%), medulloblastoma (5.5%), and other (20%). Tumours could also be classified as low-grade (64%) or high-grade (36%). Mean ADC was 1.3 for low-grade tumours and 0.9 for high-grade tumours (p=.004). Mean ADC ratios were 1.5 and 1.2 for low and high-grade tumours respectively (p=.025). There were no significant differences in ADC/ADC ratio between different histological types. ADC and ADC ratio may be useful in imaging-study based differential diagnosis of low and high-grade tumours, but they are not a substitute for an anatomical pathology study. Copyright © 2014 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Methodology and apparatus for diffuse photon imaging

DOEpatents

Feng, S.C.; Zeng, F.; Zhao, H.L.

1997-12-09

Non-invasive near infrared optical medical imaging devices for both hematoma detection in the brain and early tumor detection in the breast is achieved using image reconstruction which allows a mapping of the position dependent contrast diffusive propagation constants, which are related to the optical absorption coefficient and scattering coefficient in the tissue, at near infrared wavelengths. Spatial resolutions in the range of 5 mm for adult brain sizes and breast sizes can be achieved. The image reconstruction utilizes WKB approximation on most probable diffusion paths which has as lowest order approximation the straight line-of-sight between the plurality of sources and the plurality of detectors. The WKB approximation yields a set of linear equations in which the contrast optical absorption coefficients are the unknowns and for which signals can be generated to produce a pixel map of the contrast optical resolution of the scanned tissue. 58 figs.

Methodology and apparatus for diffuse photon mimaging

DOEpatents

Feng, Shechao C.; Zeng, Fanan; Zhao, Hui-Lin

1997-12-09

Non-invasive near infrared optical medical imaging devices for both hematoma detection in the brain and early tumor detection in the breast is achieved using image reconstruction which allows a mapping of the position dependent contrast diffusive propagation constants, which are related to the optical absorption coefficient and scattering coefficient in the tissue, at near infrared wavelengths. Spatial resolutions in the range of 5 mm for adult brain sizes and breast sizes can be achieved. The image reconstruction utilizes WKB approximation on most probable diffusion paths which has as lowest order approximation the straight line-of-sight between the plurality of sources and the plurality of detectors. The WKB approximation yields a set of linear equations in which the contrast optical absorption coefficients are the unknowns and for which signals can be generated to produce a pixel map of the contrast optical resolution of the scanned tissue.

Cilengitide in Treating Children With Refractory Primary Brain Tumors

ClinicalTrials.gov

2013-09-27

Childhood Central Nervous System Germ Cell Tumor; 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 Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Brain Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

Lenalidomide in Treating Young Patients With Recurrent, Progressive, or Refractory CNS Tumors

ClinicalTrials.gov

2013-09-27

Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Germ Cell Tumor; 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 Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Recurrent Childhood Brain Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

ABT-888 and Temozolomide in Treating Young Patients With Recurrent or Refractory CNS Tumors

ClinicalTrials.gov

2014-07-07

Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Germ Cell Tumor; 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 Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Brain Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Spinal Cord Neoplasm; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

CCDC26, CDKN2BAS, RTEL1 and TERT Polymorphisms in pediatric brain tumor susceptibility.

PubMed

Adel Fahmideh, Maral; Lavebratt, Catharina; Schüz, Joachim; Röösli, Martin; Tynes, Tore; Grotzer, Michael A; Johansen, Christoffer; Kuehni, Claudia E; Lannering, Birgitta; Prochazka, Michaela; Schmidt, Lisbeth S; Feychting, Maria

2015-08-01

The role of genetic polymorphisms in pediatric brain tumor (PBT) etiology is poorly understood. We hypothesized that single nucleotide polymorphisms (SNPs) identified in genome-wide association studies (GWAS) on adult glioma would also be associated with PBT risk. The study is based on the Cefalo study, a population-based multicenter case-control study. Saliva DNA from 245 cases and 489 controls, aged 7-19 years at diagnosis/reference date, was extracted and genotyped for 29 SNPs reported by GWAS to be significantly associated with risk of adult glioma. Data were analyzed using unconditional logistic regression. Stratified analyses were performed for two histological subtypes: astrocytoma alone and the other tumor types combined. The results indicated that four SNPs, CDKN2BAS rs4977756 (p = 0.036), rs1412829 (p = 0.037), rs2157719 (p = 0.018) and rs1063192 (p = 0.021), were associated with an increased susceptibility to PBTs, whereas the TERT rs2736100 was associated with a decreased risk (p = 0.018). Moreover, the stratified analyses showed a decreased risk of astrocytoma associated with RTEL1 rs6089953, rs6010620 and rs2297440 (p trend = 0.022, p trend = 0.042, p trend = 0.029, respectively) as well as an increased risk of this subtype associated with RTEL1 rs4809324 (p trend = 0.033). In addition, SNPs rs10464870 and rs891835 in CCDC26 were associated with an increased risk of non-astrocytoma tumor subtypes (p trend = 0.009, p trend = 0.007, respectively). Our findings indicate that SNPs in CDKN2BAS, TERT, RTEL1 and CCDC26 may be associated with the risk of PBTs. Therefore, we suggest that pediatric and adult brain tumors might share common genetic risk factors and similar etiological pathways. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Assessment of diffusion tensor imaging indices in calf muscles following postural change from standing to supine position.

PubMed

Elzibak, Alyaa H; Noseworthy, Michael D

2014-10-01

To investigate whether postural change from erect to recumbent position affects calf muscle water diffusivity. Ten healthy adults (27.2 ± 4.9 years, 3 females) were imaged at baseline (following assumption of recumbent position), and after 34 min (session 2) and 64 min (session 3) of laying supine within a 3T MRI scanner. Diffusion tensor imaging (DTI) eigenvalues, fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were evaluated in five calf muscles (anterior and posterior tibialis and triceps surae) during each of the three imaging sessions. Significant decreases were observed in all of the eigenvalues and ADC in each of the muscles with postural change. These reductions ranged from 3.2 to 6.7% and 3.4 to 7.5% for the various DTI metrics, following 34 and 64 min of supine rest, respectively (P < 0.05). No significant differences were noted in ADC or eigenvalues between the second and third imaging sessions for any muscle. FA did not change significantly with postural manipulation in any muscle compartment. Diffusion tensor imaging indices were altered with postural change. As differences were not apparent between the latter two imaging sessions, we suggest that a short supine resting period (~34 min) is sufficient for muscle diffusivity to stabilize prior to quantitative MR imaging in healthy young adults.

q-Space Deep Learning: Twelve-Fold Shorter and Model-Free Diffusion MRI Scans.

PubMed

Golkov, Vladimir; Dosovitskiy, Alexey; Sperl, Jonathan I; Menzel, Marion I; Czisch, Michael; Samann, Philipp; Brox, Thomas; Cremers, Daniel

2016-05-01

Numerous scientific fields rely on elaborate but partly suboptimal data processing pipelines. An example is diffusion magnetic resonance imaging (diffusion MRI), a non-invasive microstructure assessment method with a prominent application in neuroimaging. Advanced diffusion models providing accurate microstructural characterization so far have required long acquisition times and thus have been inapplicable for children and adults who are uncooperative, uncomfortable, or unwell. We show that the long scan time requirements are mainly due to disadvantages of classical data processing. We demonstrate how deep learning, a group of algorithms based on recent advances in the field of artificial neural networks, can be applied to reduce diffusion MRI data processing to a single optimized step. This modification allows obtaining scalar measures from advanced models at twelve-fold reduced scan time and detecting abnormalities without using diffusion models. We set a new state of the art by estimating diffusion kurtosis measures from only 12 data points and neurite orientation dispersion and density measures from only 8 data points. This allows unprecedentedly fast and robust protocols facilitating clinical routine and demonstrates how classical data processing can be streamlined by means of deep learning.

The Role of Molecular Diagnostics in the Management of Patients with Gliomas.

PubMed

Wirsching, Hans-Georg; Weller, Michael

2016-10-01

The revised World Health Organization (WHO) classification of tumors of the central nervous system of 2016 combines biology-driven molecular marker diagnostics with classical histological cancer diagnosis. Reclassification of gliomas by molecular similarity beyond histological boundaries improves outcome prediction and will increasingly guide treatment decisions. This change in paradigms implies more personalized and eventually more efficient therapeutic approaches, but the era of molecular targeted therapies for gliomas is yet at its onset. Promising results of molecularly targeted therapies in genetically less complex gliomas with circumscribed growth such as subependymal giant cell astrocytoma or pilocytic astrocytoma support further development of molecularly targeted therapies. In diffuse gliomas, several molecular markers that predict benefit from alkylating agent chemotherapy have been identified in recent years. For example, co-deletion of chromosome arms 1p and 19q predicts benefit from polychemotherapy with procarbazine, CCNU (lomustine), and vincristine (PCV) in patients with anaplastic oligodendroglioma, and the presence of 1p/19q co-deletion was integrated as a defining feature of oligodendroglial tumors in the revised WHO classification. However, the tremendous increase in knowledge of molecular drivers of diffuse gliomas on genomic, epigenetic, and gene expression levels has not yet translated into effective molecular targeted therapies. Multiple reasons account for the failure of early clinical trials of molecularly targeted therapies in diffuse gliomas, including the lack of molecular entry controls as well as pharmacokinetic and pharmacodynamics issues, but the key challenge of specifically targeting the molecular backbone of diffuse gliomas is probably extensive clonal heterogeneity. A more profound understanding of clonal selection, alternative activation of oncogenic signaling pathways, and genomic instability is warranted to identify effective

Pulmonary gas exchange efficiency during exercise breathing normoxic and hypoxic gas in adults born very preterm with low diffusion capacity.

PubMed

Duke, Joseph W; Elliott, Jonathan E; Laurie, Steven S; Beasley, Kara M; Mangum, Tyler S; Hawn, Jerold A; Gladstone, Igor M; Lovering, Andrew T

2014-09-01

Adults with a history of very preterm birth (<32 wk gestational age; PRET) have reduced lung function and significantly lower lung diffusion capacity for carbon monoxide (DLCO) relative to individuals born at term (CONT). Low DLCO may predispose PRET to diffusion limitation during exercise, particularly while breathing hypoxic gas because of a reduced O2 driving gradient and pulmonary capillary transit time. We hypothesized that PRET would have significantly worse pulmonary gas exchange efficiency [i.e., increased alveolar-to-arterial Po2 difference (AaDO2)] during exercise breathing room air or hypoxic gas (FiO2 = 0.12) compared with CONT. To test this hypothesis, we compared the AaDO2 in PRET (n = 13) with a clinically mild reduction in DLCO (72 ± 7% of predicted) and CONT (n = 14) with normal DLCO (105 ± 10% of predicted) pre- and during exercise breathing room air and hypoxic gas. Measurements of temperature-corrected arterial blood gases, and direct measure of O2 saturation (SaO2), were made prior to and during exercise at 25, 50, and 75% of peak oxygen consumption (V̇o2peak) while breathing room air and hypoxic gas. In addition to DLCO, pulmonary function and exercise capacity were significantly less in PRET. Despite PRET having low DLCO, no differences were observed in the AaDO2 or SaO2 pre- or during exercise breathing room air or hypoxic gas compared with CONT. Although our findings were unexpected, we conclude that reduced pulmonary function and low DLCO resulting from very preterm birth does not cause a measureable reduction in pulmonary gas exchange efficiency. Copyright © 2014 the American Physiological Society.

Effects of insulin resistance on white matter microstructure in middle-aged and older adults

PubMed Central

Coutu, Jean-Philippe; Rosas, H. Diana; Salat, David H.

2014-01-01

Objective: To investigate the potential relationship between insulin resistance (IR) and white matter (WM) microstructure using diffusion tensor imaging in cognitively healthy middle-aged and older adults. Methods: Diffusion tensor imaging was acquired from 127 individuals (age range 41–86 years). IR was evaluated by the homeostasis model assessment of IR (HOMA-IR). Participants were divided into 2 groups based on HOMA-IR values: “high HOMA-IR” (≥2.5, n = 27) and “low HOMA-IR” (<2.5, n = 100). Cross-sectional voxel-based comparisons were performed using Tract-Based Spatial Statistics and anatomically defined regions of interest analysis. Results: The high HOMA-IR group demonstrated decreased axial diffusivity broadly throughout the cerebral WM in areas such as the corpus callosum, corona radiata, cerebral peduncle, posterior thalamic radiation, and right superior longitudinal fasciculus, and WM underlying the frontal, parietal, and temporal lobes, as well as decreased fractional anisotropy in the body and genu of corpus callosum and parts of the superior and anterior corona radiata, compared with the low HOMA-IR group, independent of age, WM signal abnormality volume, and antihypertensive medication status. These regions additionally demonstrated linear associations between diffusion measures and HOMA-IR across all subjects, with higher HOMA-IR values being correlated with lower axial diffusivity. Conclusions: In generally healthy adults, greater IR is associated with alterations in WM tissue integrity. These cross-sectional findings suggest that IR contributes to WM microstructural alterations in middle-aged and older adults. PMID:24771537

Frontal networks in adults with autism spectrum disorder.

PubMed

Catani, Marco; Dell'Acqua, Flavio; Budisavljevic, Sanja; Howells, Henrietta; Thiebaut de Schotten, Michel; Froudist-Walsh, Seán; D'Anna, Lucio; Thompson, Abigail; Sandrone, Stefano; Bullmore, Edward T; Suckling, John; Baron-Cohen, Simon; Lombardo, Michael V; Wheelwright, Sally J; Chakrabarti, Bhismadev; Lai, Meng-Chuan; Ruigrok, Amber N V; Leemans, Alexander; Ecker, Christine; Consortium, Mrc Aims; Craig, Michael C; Murphy, Declan G M

2016-02-01

It has been postulated that autism spectrum disorder is underpinned by an 'atypical connectivity' involving higher-order association brain regions. To test this hypothesis in a large cohort of adults with autism spectrum disorder we compared the white matter networks of 61 adult males with autism spectrum disorder and 61 neurotypical controls, using two complementary approaches to diffusion tensor magnetic resonance imaging. First, we applied tract-based spatial statistics, a 'whole brain' non-hypothesis driven method, to identify differences in white matter networks in adults with autism spectrum disorder. Following this we used a tract-specific analysis, based on tractography, to carry out a more detailed analysis of individual tracts identified by tract-based spatial statistics. Finally, within the autism spectrum disorder group, we studied the relationship between diffusion measures and autistic symptom severity. Tract-based spatial statistics revealed that autism spectrum disorder was associated with significantly reduced fractional anisotropy in regions that included frontal lobe pathways. Tractography analysis of these specific pathways showed increased mean and perpendicular diffusivity, and reduced number of streamlines in the anterior and long segments of the arcuate fasciculus, cingulum and uncinate--predominantly in the left hemisphere. Abnormalities were also evident in the anterior portions of the corpus callosum connecting left and right frontal lobes. The degree of microstructural alteration of the arcuate and uncinate fasciculi was associated with severity of symptoms in language and social reciprocity in childhood. Our results indicated that autism spectrum disorder is a developmental condition associated with abnormal connectivity of the frontal lobes. Furthermore our findings showed that male adults with autism spectrum disorder have regional differences in brain anatomy, which correlate with specific aspects of autistic symptoms. Overall these

Palbociclib Isethionate in Treating Younger Patients With Recurrent, Progressive, or Refractory Central Nervous System Tumors

ClinicalTrials.gov

2017-09-27

Childhood Choroid Plexus Tumor; Childhood Ependymoblastoma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Recurrent Childhood Anaplastic Astrocytoma; Recurrent Childhood Anaplastic Oligoastrocytoma; Recurrent Childhood Anaplastic Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Giant Cell Glioblastoma; Recurrent Childhood Glioblastoma; Recurrent Childhood Gliomatosis Cerebri; Recurrent Childhood Gliosarcoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor

Diffusion Tensor Imaging Correlates of Reading Ability in Dysfluent and Non-Impaired Readers

ERIC Educational Resources Information Center

Lebel, Catherine; Shaywitz, Bennett; Holahan, John; Shaywitz, Sally; Marchione, Karen; Beaulieu, Christian

2013-01-01

Many children and adults have specific reading disabilities; insight into the brain structure underlying these difficulties is evolving from imaging. Previous research highlights the left temporal-parietal white matter as important in reading, yet the degree of involvement of other areas remains unclear. Diffusion tensor imaging (DTI) and…

FRACTIONAL PEARSON DIFFUSIONS.

PubMed

Leonenko, Nikolai N; Meerschaert, Mark M; Sikorskii, Alla

2013-07-15

Pearson diffusions are governed by diffusion equations with polynomial coefficients. Fractional Pearson diffusions are governed by the corresponding time-fractional diffusion equation. They are useful for modeling sub-diffusive phenomena, caused by particle sticking and trapping. This paper provides explicit strong solutions for fractional Pearson diffusions, using spectral methods. It also presents stochastic solutions, using a non-Markovian inverse stable time change.

Remote intracranial recurrence of IDH mutant gliomas is associated with TP53 mutations and an 8q gain

PubMed Central

Nakae, Shunsuke; Kato, Takema; Murayama, Kazuhiro; Sasaki, Hikaru; Abe, Masato; Kumon, Masanobu; Kumai, Tadashi; Yamashiro, Kei; Inamasu, Joji; Hasegawa, Mitsuhiro; Kurahashi, Hiroki; Hirose, Yuichi

2017-01-01

Most IDH mutant gliomas harbor either 1p/19q co-deletions or TP53 mutation; 1p/19q co-deleted tumors have significantly better prognoses than tumors harboring TP53 mutations. To investigate the clinical factors that contribute to differences in tumor progression of IDH mutant gliomas, we classified recurrent tumor patterns based on MRI and correlated these patterns with their genomic characterization. Accordingly, in IDH mutant gliomas (N = 66), 1p/19 co-deleted gliomas only recurred locally, whereas TP53 mutant gliomas recurred both locally and in remote intracranial regions. In addition, diffuse tensor imaging suggested that remote intracranial recurrence in the astrocytomas, IDH-mutant with TP53 mutations may occur along major fiber bundles. Remotely recurrent tumors resulted in a higher mortality and significantly harbored an 8q gain; astrocytomas with an 8q gain resulted in significantly shorter overall survival than those without an 8q gain. OncoScan® arrays and next-generation sequencing revealed specific 8q regions (i.e., between 8q22 and 8q24) show a high copy number. In conclusion, only tumors with TP53 mutations showed patterns of remote recurrence in IDH mutant gliomas. Furthermore, an 8q gain was significantly associated with remote intracranial recurrence and can be considered a poor prognostic factor in astrocytomas, IDH-mutant. PMID:29156679

Characterization of R132H mutation-specific IDH1 antibody binding in brain tumors.

PubMed

Capper, David; Weissert, Susanne; Balss, Jörg; Habel, Antje; Meyer, Jochen; Jäger, Diana; Ackermann, Ulrike; Tessmer, Claudia; Korshunov, Andrey; Zentgraf, Hanswalter; Hartmann, Christian; von Deimling, Andreas

2010-01-01

Heterozygous point mutations of isocitrate dehydrogenase (IDH)1 codon 132 are frequent in grade II and III gliomas. Recently, we reported an antibody specific for the IDH1R132H mutation. Here we investigate the capability of this antibody to differentiate wild type and mutated IDH1 protein in central nervous system (CNS) tumors by Western blot and immunohistochemistry. Results of protein analysis are correlated to sequencing data. In Western blot, anti-IDH1R132H mouse monoclonal antibody mIDH1R132H detected a specific band only in mutated tumors. Immunohistochemistry of 345 primary brain tumors demonstrated a strong cytoplasmic and weaker nuclear staining in 122 cases. Correlation with direct sequencing of 186 cases resulted in consensus of 177 cases. Genetic retesting of cases with conflicting findings resulted in a match of 186/186 cases, with all discrepancies resolving in favor of immunohistochemistry. Intriguing is the ability of mIDH1R132H to detect single infiltrating tumor cells. The very high frequency and the distribution of this mutation among specific brain tumor entities allow the highly sensitive and specific discrimination of various tumors by immunohistochemistry, such as anaplastic astrocytoma from primary glioblastoma or diffuse astrocytoma World Health Organization (WHO) grade II from pilocytic astrocytoma or ependymoma. Noteworthy is the discrimination of the infiltrating edge of tumors with IDH1 mutation from reactive gliosis.

Orientation diffusions.

PubMed

Perona, P

1998-01-01

Diffusions are useful for image processing and computer vision because they provide a convenient way of smoothing noisy data, analyzing images at multiple scales, and enhancing discontinuities. A number of diffusions of image brightness have been defined and studied so far; they may be applied to scalar and vector-valued quantities that are naturally associated with intervals of either the real line, or other flat manifolds. Some quantities of interest in computer vision, and other areas of engineering that deal with images, are defined on curved manifolds;typical examples are orientation and hue that are defined on the circle. Generalizing brightness diffusions to orientation is not straightforward, especially in the case where a discrete implementation is sought. An example of what may go wrong is presented.A method is proposed to define diffusions of orientation-like quantities. First a definition in the continuum is discussed, then a discrete orientation diffusion is proposed. The behavior of such diffusions is explored both analytically and experimentally. It is shown how such orientation diffusions contain a nonlinearity that is reminiscent of edge-process and anisotropic diffusion. A number of open questions are proposed at the end.

Diffusion of Zonal Variables Using Node-Centered Diffusion Solver

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, T B

2007-08-06

Tom Kaiser [1] has done some preliminary work to use the node-centered diffusion solver (originally developed by T. Palmer [2]) in Kull for diffusion of zonal variables such as electron temperature. To avoid numerical diffusion, Tom used a scheme developed by Shestakov et al. [3] and found their scheme could, in the vicinity of steep gradients, decouple nearest-neighbor zonal sub-meshes leading to 'alternating-zone' (red-black mode) errors. Tom extended their scheme to couple the sub-meshes with appropriate chosen artificial diffusion and thereby solved the 'alternating-zone' problem. Because the choice of the artificial diffusion coefficient could be very delicate, it is desirablemore » to use a scheme that does not require the artificial diffusion but still able to avoid both numerical diffusion and the 'alternating-zone' problem. In this document we present such a scheme.« less

Combination therapy with thalidomide, temozolomide and tamoxifen improves quality of life in patients with malignant astrocytomas.

PubMed

Rabbani, Golam; Benzil, Deborah; Wallam, Mohammed N; Chen, Benjamin; Hoang, Albert; Kancherla, Ram; Ahmed, Tauseef

2007-01-01

Patients with malignant astrocytomas (MA) have a poor survival rate despite surgery, radiation therapy (RT), and chemotherapy (CT). Patients deteriorate rapidly with decreasing quality of life (QoL). The purpose of the current study was to determine the safety and efficacy, including QoL evaluation, of oral therapy with temozolomide, thalidomide, and tamoxifen (TTT) in patients with MA in an Institutional Review Board (IRB)-approved, prospective trial. Twenty-three patients met the eligibility requirements and were enrolled after informed consent was signed. After baseline testing, patients received temozolomide 75 mg/m2 orally (p.o.) for the first 21 days, thalidomide 100 mg p.o. daily, and tamoxifen 100 mg p.o. daily for each 28-day cycle. Treatment continued until disease progression. Primary outcome measurements were survival (Kaplan-Meier analysis), response to treatment, toxicity (National Cancer Institute's Common Toxicity Criterion) and QoL evaluation. The Kaplan-Meier analysis showed that survival time from diagnosis was 78.4+/-15 weeks with a median survival of 54.6 weeks and from date of enrollment was 46.1+/-10 weeks with median survival of 33.3 weeks. Toxicity was limited to 5 patients with deep venous thrombosis (DVT), 2 of whom had pulmonary emboli (PE). All recovered with anticoagulation therapy and none suffered long term sequelae. Several QoL measures, including the global health status scores (p=0.003), were significantly improved after 2 cycles of treatment compared to the baseline assessment. The combination of temozolomide, thalidomide and tamoxifen administered as outpatient oral therapy resulted in significantly improved QoL for patients with MA without significant toxicity.

Primitive Neuroectodermal Tumor Presenting with Diffuse Leptomeningeal Involvement in a 55-Year-Old Woman: A Case Report and Brief Summary of Current Diagnostic Tests and Treatment

PubMed Central

Kalidindi, Navya; Torres, Carlos H.; Michaud, Jean; Zwicker, Jocelyn Christine

2014-01-01

Primitive neuroectodermal tumors (PNETs) are typically present as masses in children and adolescents, but rarely in adults. Diagnoses, management strategies, and prognostication factors are not well established in adult cases of PNETs. We describe the case of a central nervous system PNET diagnosed in a 55-year-old woman presenting with a sudden onset of symptoms consisting of increased intracranial pressure and findings of diffuse leptomeningeal enhancement and a small medullary lesion seen on MRI. Amongst the small database of PNETs diagnosed in adults, our case report stands out as one of few cases describing a primarily leptomeningeal PNET diagnosed on biopsy. We also review the literature on PNETs presenting with diffuse leptomeningeal disease and the treatment of PNETs in the adult population. PMID:25202261

On the Origins of the Term and Meanings of "Adult Education" in the United States.

ERIC Educational Resources Information Center

Stubblefield, Harold W.; Rachal, John R.

1992-01-01

The term "adult education" was used in the United States in the late nineteenth century. Melvil Dewey developed a typology of adult education, and Henry Leipziger promoted New York City's Free Lectures program as an institute of liberal adult education. Leipziger's advocacy was largely responsible for the diffusion of the new term in its…

The Harrison Diffusion Kinetics Regimes in Solute Grain Boundary Diffusion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Belova, Irina; Fiedler, T; Kulkarni, Nagraj S

2012-01-01

Knowledge of the limits of the principal Harrison kinetics regimes (Type-A, B and C) for grain boundary diffusion is very important for the correct analysis of the depth profiles in a tracer diffusion experiment. These regimes for self-diffusion have been extensively studied in the past by making use of the phenomenological Lattice Monte Carlo (LMC) method with the result that the limits are now well established. The relationship of those self-diffusion limits to the corresponding ones for solute diffusion in the presence of solute segregation to the grain boundaries remains unclear. In the present study, the influence of solute segregationmore » on the limits is investigated with the LMC method for the well-known parallel grain boundary slab model by showing the equivalence of two diffusion models. It is shown which diffusion parameters are useful for identifying the limits of the Harrison kinetics regimes for solute grain boundary diffusion. It is also shown how the measured segregation factor from the diffusion experiment in the Harrison Type-B kinetics regime may differ from the global segregation factor.« less

Diffusion MRI: Pitfalls, literature review and future directions of research in mild traumatic brain injury.

PubMed

Delouche, Aurélie; Attyé, Arnaud; Heck, Olivier; Grand, Sylvie; Kastler, Adrian; Lamalle, Laurent; Renard, Felix; Krainik, Alexandre

2016-01-01

Mild traumatic brain injury (mTBI) is a leading cause of disability in adults, many of whom report a distressing combination of physical, emotional and cognitive symptoms, collectively known as post-concussion syndrome, that persist after the injury. Significant developments in magnetic resonance diffusion imaging, involving voxel-based quantitative analysis through the measurement of fractional anisotropy or mean diffusivity, have enhanced our knowledge on the different stages of mTBI pathophysiology. Other diffusion imaging-derived techniques, including diffusion kurtosis imaging with multi-shell diffusion and high-order tractography models, have recently demonstrated their usefulness in mTBI. Our review starts by briefly outlining the physical basis of diffusion tensor imaging including the pitfalls for use in brain trauma, before discussing findings from diagnostic trials testing its usefulness in assessing brain structural changes in patients with mTBI. Use of different post-processing techniques for the diffusion imaging data, identified the corpus callosum as the most frequently injured structure in mTBI, particularly at sub-acute and chronic stages, and a crucial location for evaluating functional outcome. However, structural changes appear too subtle for identification using traditional diffusion biomarkers, thus disallowing expansion of these techniques into clinical practice. In this regard, more advanced diffusion techniques are promising in the assessment of this complex disease. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Turkish and Moroccan Young Adults in the Netherlands: The Relationship Between Acculturation and Psychological Problems.

PubMed

Özbek, Emel; Bongers, Ilja L; Lobbestael, Jill; van Nieuwenhuizen, Chijs

2015-12-01

This study investigated the relationship between acculturation and psychological problems in Turkish and Moroccan young adults living in the Netherlands. A sample of 131 healthy young adults aged between 18 and 24 years old, with a Turkish or Moroccan background was recruited using snowball sampling. Data on acculturation, internalizing and externalizing problems, beliefs about psychological problems, attributions of psychological problems and barriers to care were collected and analyzed using Latent Class Analysis and multinomial logistic regression. Three acculturation classes were identified in moderately to highly educated, healthy Turkish or Moroccan young adults: integration, separation and diffusion. None of the participants in the sample were marginalized or assimilated. Young adults reporting diffuse acculturation reported more internalizing and externalizing problems than those who were integrated or separated. Separated young adults reported experiencing more practical barriers to care than integrated young adults. Further research with a larger sample, including young adult migrants using mental health services, is required to improve our understanding of acculturation, psychological problems and barriers to care in this population. Including experiences of discrimination in the model might improve our understanding of the relationship between different forms of acculturation and psychological problems.

Test of the diffusing-diffusivity mechanism using near-wall colloidal dynamics

NASA Astrophysics Data System (ADS)

Matse, Mpumelelo; Chubynsky, Mykyta V.; Bechhoefer, John

2017-10-01

The mechanism of diffusing diffusivity predicts that, in environments where the diffusivity changes gradually, the displacement distribution becomes non-Gaussian, even though the mean-square displacement grows linearly with time. Here, we report single-particle tracking measurements of the diffusion of colloidal spheres near a planar substrate. Because the local effective diffusivity is known, we have been able to carry out a direct test of this mechanism for diffusion in inhomogeneous media.

Controllable uncertain opinion diffusion under confidence bound and unpredicted diffusion probability

NASA Astrophysics Data System (ADS)

Yan, Fuhan; Li, Zhaofeng; Jiang, Yichuan

2016-05-01

The issues of modeling and analyzing diffusion in social networks have been extensively studied in the last few decades. Recently, many studies focus on uncertain diffusion process. The uncertainty of diffusion process means that the diffusion probability is unpredicted because of some complex factors. For instance, the variety of individuals' opinions is an important factor that can cause uncertainty of diffusion probability. In detail, the difference between opinions can influence the diffusion probability, and then the evolution of opinions will cause the uncertainty of diffusion probability. It is known that controlling the diffusion process is important in the context of viral marketing and political propaganda. However, previous methods are hardly feasible to control the uncertain diffusion process of individual opinion. In this paper, we present suitable strategy to control this diffusion process based on the approximate estimation of the uncertain factors. We formulate a model in which the diffusion probability is influenced by the distance between opinions, and briefly discuss the properties of the diffusion model. Then, we present an optimization problem at the background of voting to show how to control this uncertain diffusion process. In detail, it is assumed that each individual can choose one of the two candidates or abstention based on his/her opinion. Then, we present strategy to set suitable initiators and their opinions so that the advantage of one candidate will be maximized at the end of diffusion. The results show that traditional influence maximization algorithms are not applicable to this problem, and our algorithm can achieve expected performance.

Racial Differences in Gray Matter Integrity by Diffusion Tensor in Black and White Octogenarians.

PubMed

Liu, Ge; Allen, Ben; Lopez, Oscar; Aizenstein, Howard; Boudreau, Robert; Newman, Anne; Yaffe, Kristine; Kritchevsky, Stephen; Launer, Lenore; Satterfield, Suzanne; Simonsick, Eleanor; Rosano, Caterina

2015-01-01

To quantify racial differences in brain structural characteristics in white and black octogenarians, and to examine whether these characteristics contribute to cognition. Cross-sectional study of 283 adults 79-89 years old (59.4% white;42.0% women) with data on gray matter integrity via diffusion tensor imaging (mean diffusivity), gray matter atrophy (GMA), white matter hyperintensities (WMH), literacy, smoking, drinking, income, hypertension and diabetes. Participants were recruited from an ongoing epidemiological study of older adults living in the community with a range of chronic conditions, physical and cognitive function. Standardized betas (sβ) of neuroimaging markers predicting Digit Symbol Substitution Test (DSST) and Modified Mini-Mental State Examination (3MS) scores were computed in multivariable regression models stratified by race. Compared to whites, blacks had lower DSST (p=0.001) and lower 3MS (p=0.006), but also lower mean diffusivity (i.e. higher gray matter microstructural integrity, p=0.032), independent of gender, income, literacy, body mass index, diabetes and drinking habits. Racial differences were not significant for WMH (p=0.062) or GMA (p=0.4). Among blacks, mean diffusivity and WMH were associated with DSST (sβ=-.209, p=0.037 and -.211, p=.038, respectively) independent of each other and other covariates; among whites, mean diffusivity, but not WMH, was significantly associated with DSST and 3MS (sβ =-.277, p=.002 and -.250, p=0.029, respectively). In this cohort of octogenarians living in the community, blacks appeared to have higher microstructural integrity of gray matter as compared to whites. This neuroimaging marker was related to higher cognition even in the presence of WMH and other cardiovascular conditions. If confirmed, these findings suggest microstructural gray matter integrity may be a target to improve cognition, especially among blacks who survive to very old age with a range of chronic cardiovascular conditions.

AZD2171 in Treating Young Patients With Recurrent, Progressive, or Refractory Primary CNS Tumors

ClinicalTrials.gov

2016-03-04

Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Germ Cell Tumor; Childhood Cerebral Anaplastic Astrocytoma; Childhood Cerebral Astrocytoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood Infratentorial Ependymoma; Childhood Oligodendroglioma; Childhood Spinal Cord Neoplasm; Childhood Supratentorial Ependymoma; Recurrent Childhood Brain Neoplasm; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway Glioma

Microfabricated diffusion source

DOEpatents

Oborny, Michael C [Albuquerque, NM; Frye-Mason, Gregory C [Cedar Crest, NM; Manginell, Ronald P [Albuquerque, NM

2008-07-15

A microfabricated diffusion source to provide for a controlled diffusion rate of a vapor comprises a porous reservoir formed in a substrate that can be filled with a liquid, a headspace cavity for evaporation of the vapor therein, a diffusion channel to provide a controlled diffusion of the vapor, and an outlet to release the vapor into a gas stream. The microfabricated diffusion source can provide a calibration standard for a microanalytical system. The microanalytical system with an integral diffusion source can be fabricated with microelectromechanical systems technologies.

Spatial Mapping of Translational Diffusion Coefficients Using Diffusion Tensor Imaging: A Mathematical Description

PubMed Central

SHETTY, ANIL N.; CHIANG, SHARON; MALETIC-SAVATIC, MIRJANA; KASPRIAN, GREGOR; VANNUCCI, MARINA; LEE, WESLEY

2016-01-01

In this article, we discuss the theoretical background for diffusion weighted imaging and diffusion tensor imaging. Molecular diffusion is a random process involving thermal Brownian motion. In biological tissues, the underlying microstructures restrict the diffusion of water molecules, making diffusion directionally dependent. Water diffusion in tissue is mathematically characterized by the diffusion tensor, the elements of which contain information about the magnitude and direction of diffusion and is a function of the coordinate system. Thus, it is possible to generate contrast in tissue based primarily on diffusion effects. Expressing diffusion in terms of the measured diffusion coefficient (eigenvalue) in any one direction can lead to errors. Nowhere is this more evident than in white matter, due to the preferential orientation of myelin fibers. The directional dependency is removed by diagonalization of the diffusion tensor, which then yields a set of three eigenvalues and eigenvectors, representing the magnitude and direction of the three orthogonal axes of the diffusion ellipsoid, respectively. For example, the eigenvalue corresponding to the eigenvector along the long axis of the fiber corresponds qualitatively to diffusion with least restriction. Determination of the principal values of the diffusion tensor and various anisotropic indices provides structural information. We review the use of diffusion measurements using the modified Stejskal–Tanner diffusion equation. The anisotropy is analyzed by decomposing the diffusion tensor based on symmetrical properties describing the geometry of diffusion tensor. We further describe diffusion tensor properties in visualizing fiber tract organization of the human brain. PMID:27441031

Vorinostat and Temozolomide in Treating Young Patients With Relapsed or Refractory Primary Brain Tumors or Spinal Cord Tumors

ClinicalTrials.gov

2013-05-01

Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Choriocarcinoma; Childhood Central Nervous System Embryonal Tumor; Childhood Central Nervous System Germinoma; Childhood Central Nervous System Mixed Germ Cell Tumor; Childhood Central Nervous System Teratoma; Childhood Central Nervous System Yolk Sac Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood 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 Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Extra-adrenal Paraganglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Central Nervous System Embryonal Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Spinal Cord Neoplasm; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

The importance of age-related differences in prospective memory: Evidence from diffusion model analyses.

PubMed

Ball, B Hunter; Aschenbrenner, Andrew J

2017-06-09

Event-based prospective memory (PM) refers to relying on environmental cues to trigger retrieval of a deferred action plan from long-term memory. Considerable research has demonstrated PM declines with increased age. Despite efforts to better characterize the attentional processes that underlie these decrements, the majority of research has relied on measures of central tendency to inform theoretical accounts of PM that may not entirely capture the underlying dynamics involved in allocating attention to intention-relevant information. The purpose of the current study was to examine the utility of the diffusion model to better understand the cognitive processes underlying age-related differences in PM. Results showed that emphasizing the importance of the PM intention increased cue detection selectively for older adults. Standard cost analyses revealed that PM importance increased mean response times and accuracy, but not differentially for young and older adults. Consistent with this finding, diffusion model analyses demonstrated that PM importance increased response caution as evidenced by increased boundary separation. However, the selective benefit in cue detection for older adults may reflect peripheral target-checking processes as indicated by changes in nondecision time. These findings highlight the use of modeling techniques to better characterize the processes underlying the relations among aging, attention, and PM.

High-throughput immunohistochemical profiling of primary brain tumors and non-neoplastic systemic organs with a specific antibody against the mutant isocitrate dehydrogenase 1 R132H protein.

PubMed

Ikota, Hayato; Nobusawa, Sumihito; Tanaka, Yuko; Yokoo, Hideaki; Nakazato, Yoichi

2011-04-01

Isocitrate dehydrogenase 1 (IDH1) mutations are common in grade II-III diffuse gliomas and secondary glioblastomas. The aim of this study is to investigate the staining pattern of mIDH1R132H, an antibody specific to mutant IDH1 protein, in primary brain tumors and non-neoplastic systemic organs. Eight of 13 diffuse astrocytomas, 1 of 6 anaplastic astrocytomas, 9 of 11 oligodendrogliomas, 15 of 22 anaplastic oligodendrogliomas, 6 of 7 oligoastrocytomas, and 5 of 8 anaplastic oligoastrocytomas showed both cytoplasmic and nuclear positivity. Two of 25 atypical meningiomas and 2 of 42 pituitary adenomas were positive for mIDH1R132H. The following non-neoplastic systemic organs showed positivity in the cytoplasm alone: the myocardium, peribronchial glands, interlobular ducts of the salivary gland, gastric fundic gland, columnar epithelia of the large bowel, hepatocytes, centroacinar cells, the intercalated ducts of the pancreas, renal proximal and distal tubules, adrenocortex, ovarian granulosa cells, and the choroid plexus epithelia. It was concluded that the immunopositivity detected in non-neoplastic systemic organs was due to cross-reactivity, because immunohistochemistry with an anti-mitochondrial antibody revealed that the mIDH1R132H staining pattern was identical to that of the mitochondria. Therefore, mIDH1R132H positivity should only be considered to be validated when a cell shows both cytoplasmic and nuclear staining.

Development and aging of the healthy human brain uncinate fasciculus across the lifespan using diffusion tensor tractography.

PubMed

Hasan, Khader M; Iftikhar, Amal; Kamali, Arash; Kramer, Larry A; Ashtari, Manzar; Cirino, Paul T; Papanicolaou, Andrew C; Fletcher, Jack M; Ewing-Cobbs, Linda

2009-06-18

The human brain uncinate fasciculus (UF) is an important cortico-cortical white matter pathway that directly connects the frontal and temporal lobes, although there is a lack of conclusive support for its exact functional role. Using diffusion tensor tractography, we extracted the UF, calculated its volume and normalized it with respect to each subject's intracranial volume (ICV) and analyzed its corresponding DTI metrics bilaterally on a cohort of 108 right-handed children and adults aged 7-68 years. Results showed inverted U-shaped curves for fractional anisotropy (FA) with advancing age and U-shaped curves for radial and axial diffusivities reflecting white matter progressive and regressive myelination and coherence dynamics that continue into young adulthood. The mean FA values of the UF were significantly larger on the left side in children (p=0.05), adults (p=0.0012) and the entire sample (p=0.0002). The FA leftward asymmetry (Left>Right) is shown to be due to increased leftward asymmetry in the axial diffusivity (p<0.0001) and a lack of asymmetry (p>0.23) for the radial diffusivity. This is the first study to provide baseline normative macro and microstructural age trajectories of the human UF across the lifespan. Results of this study may lend themselves to better understanding of UF role in future behavioral and clinical studies.

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

PubMed

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

2010-04-26

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

Longitudinal diffusion changes following postoperative delirium in older people without dementia.

PubMed

Cavallari, Michele; Dai, Weiying; Guttmann, Charles R G; Meier, Dominik S; Ngo, Long H; Hshieh, Tammy T; Fong, Tamara G; Schmitt, Eva; Press, Daniel Z; Travison, Thomas G; Marcantonio, Edward R; Jones, Richard N; Inouye, Sharon K; Alsop, David C

2017-09-05

To investigate the effect of postoperative delirium on longitudinal brain microstructural changes, as measured by diffusion tensor imaging. We studied a subset of the larger Successful Aging after Elective Surgery (SAGES) study cohort of older adults (≥70 years) without dementia undergoing elective surgery: 113 participants who had diffusion tensor imaging before and 1 year after surgery. Postoperative delirium severity and occurrence were assessed during the hospital stay using the Confusion Assessment Method and a validated chart review method. We investigated the association of delirium severity and occurrence with longitudinal diffusion changes across 1 year, adjusting for age, sex, vascular comorbidity, and baseline cognitive performance. We also assessed the association between changes in diffusion and cognitive performance across the 1-year follow-up period, adjusting for age, sex, education, and baseline cognitive performance. Postoperative delirium occurred in 25 participants (22%). Delirium severity and occurrence were associated with longitudinal diffusion changes in the periventricular, frontal, and temporal white matter. Diffusion changes were also associated with changes in cognitive performance across 1 year, although the cognitive changes did not show significant association with delirium severity or occurrence. Our study raises the possibility that delirium has an effect on the development of brain microstructural abnormalities, which may reflect brain changes underlying cognitive trajectories. Future studies are warranted to clarify whether delirium is the driving factor of the observed changes or rather a correlate of a vulnerable brain that is at high risk for neurodegenerative processes. © 2017 American Academy of Neurology.

Measurement tensors in diffusion MRI: generalizing the concept of diffusion encoding.

PubMed

Westin, Carl-Fredrik; Szczepankiewicz, Filip; Pasternak, Ofer; Ozarslan, Evren; Topgaard, Daniel; Knutsson, Hans; Nilsson, Markus

2014-01-01

In traditional diffusion MRI, short pulsed field gradients (PFG) are used for the diffusion encoding. The standard Stejskal-Tanner sequence uses one single pair of such gradients, known as single-PFG (sPFG). In this work we describe how trajectories in q-space can be used for diffusion encoding. We discuss how such encoding enables the extension of the well-known scalar b-value to a tensor-valued entity we call the diffusion measurement tensor. The new measurements contain information about higher order diffusion propagator covariances not present in sPFG. As an example analysis, we use this new information to estimate a Gaussian distribution over diffusion tensors in each voxel, described by its mean (a diffusion tensor) and its covariance (a 4th order tensor).

White matter and neurocognitive changes in adults with chronic traumatic brain injury.

PubMed

Kennedy, Mary R T; Wozniak, Jeffrey R; Muetzel, Ryan L; Mueller, Bryon A; Chiou, Hsin-Huei; Pantekoek, Kari; Lim, Kelvin O

2009-01-01

Diffusion tensor imaging was used to investigate white matter (WM) integrity in adults with traumatic brain injury (TBI) and healthy adults as controls. Adults with TBI had sustained severe vehicular injuries on the average of 7 years earlier. A multivariate analysis of covariance with verbal IQ as the covariate revealed that adults with TBI had lower fractional anisotropy and higher mean diffusivity than controls, specifically in the three regions of interest (ROIs), the centrum semiovale (CS), the superior frontal (SPF), and the inferior frontal (INF). Adults with TBI averaged in the normal range in motor speed and two of three executive functions and were below average in delayed verbal recall and inhibition, whereas controls were above average. Time since injury, but not age, was associated with WM changes in the SPF ROI, whereas age, but not time since injury, was associated with WM changes in the INF ROI, suggesting that the effects of WM on time since injury may interact with age. To understand the utility of WM changes in chronic recovery, larger sample sizes are needed to investigate associations between cognition and WM integrity of severely injured individuals who have substantial cognitive impairment compared to severely injured individuals with little cognitive impairment. (JINS, 2009, 15, 130-136.).

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

PubMed

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

2016-08-10

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

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

PubMed

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

2011-08-01

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

Diffusion of an Evidence-Based Smoking Cessation Intervention Through Facebook: A Randomized Controlled Trial.

PubMed

Cobb, Nathan K; Jacobs, Megan A; Wileyto, Paul; Valente, Thomas; Graham, Amanda L

2016-06-01

To examine the diffusion of an evidence-based smoking cessation application ("app") through Facebook social networks and identify specific intervention components that accelerate diffusion. Between December 2012 and October 2013, we recruited adult US smokers ("seeds") via Facebook advertising and randomized them to 1 of 12 app variants using a factorial design. App variants targeted components of diffusion: duration of use (t), "contagiousness" (β), and number of contacts (Z). The primary outcome was the reproductive ratio (R), defined as the number of individuals installing the app ("descendants") divided by the number of a seed participant's Facebook friends. We randomized 9042 smokers. App utilization metrics demonstrated between-variant differences in expected directions. The highest level of diffusion (R = 0.087) occurred when we combined active contagion strategies with strategies to increase duration of use (incidence rate ratio = 9.99; 95% confidence interval = 5.58, 17.91; P < .001). Involving nonsmokers did not affect diffusion. The maximal R value (0.087) is sufficient to increase the numbers of individuals receiving treatment if applied on a large scale. Online interventions can be designed a priori to spread through social networks.

Introduction for Diffusion Chamber Culture Symposium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carsten, A. L.

The diffusion-chamber system has been applied to studies of cell kinetics, progenitor cell quantitation, humoral effects, immunological effects, cytogenetics, organogenesis, and the cellular effects of drugs and physical factors such as radiation, hypoxia, etc. Chamber contents have been analyzed by clot dissolution with measuring of cell content, limiting dilution evaluation, radionuclide utilization (tritiated thymidine labeling), growth of colony number, size and type, CFU-S or CFU-C content, or proliferation by secondary culture in mice or in vitro systems, and chromosome changes. Cell types ranging from embryonal tissues to adult normal and neoplastic tissues have been grown in hosts across species barriers.more » Advantages and disadvantages of this system are discussed.« less

Progressive gender differences of structural brain networks in healthy adults: a longitudinal, diffusion tensor imaging study.

PubMed

Sun, Yu; Lee, Renick; Chen, Yu; Collinson, Simon; Thakor, Nitish; Bezerianos, Anastasios; Sim, Kang

2015-01-01

Sexual dimorphism in the brain maturation during childhood and adolescence has been repeatedly documented, which may underlie the differences in behaviors and cognitive performance. However, our understanding of how gender modulates the development of structural connectome in healthy adults is still not entirely clear. Here we utilized graph theoretical analysis of longitudinal diffusion tensor imaging data over a five-year period to investigate the progressive gender differences of brain network topology. The brain networks of both genders showed prominent economical "small-world" architecture (high local clustering and short paths between nodes). Additional analysis revealed a more economical "small-world" architecture in females as well as a greater global efficiency in males regardless of scan time point. At the regional level, both increased and decreased efficiency were found across the cerebral cortex for both males and females, indicating a compensation mechanism of cortical network reorganization over time. Furthermore, we found that weighted clustering coefficient exhibited significant gender-time interactions, implying different development trends between males and females. Moreover, several specific brain regions (e.g., insula, superior temporal gyrus, cuneus, putamen, and parahippocampal gyrus) exhibited different development trajectories between males and females. Our findings further prove the presence of sexual dimorphism in brain structures that may underlie gender differences in behavioral and cognitive functioning. The sex-specific progress trajectories in brain connectome revealed in this work provide an important foundation to delineate the gender related pathophysiological mechanisms in various neuropsychiatric disorders, which may potentially guide the development of sex-specific treatments for these devastating brain disorders.

Fluorescence-guided surgery with 5-aminolevulinic acid for resection of brain tumors in children--a technical report.

PubMed

Beez, Thomas; Sarikaya-Seiwert, Sevgi; Steiger, Hans-Jakob; Hänggi, Daniel

2014-03-01

5-aminolevulinic acid (5-ALA) can be used as an adjunct for the surgery of adult malignant glioma and improves the rate of gross total resection and patient survival. So far, only three casuistic reports of fluorescence-guided surgery used in children have been published. We report our pilot series of 16 pediatric brain tumors treated with 5-ALA. Sixteen patients (mean age 9 years, range 1-16 years) received a standardized 5-ALA dose according to the published protocol after informed parental consent. The fluorescence status (positive versus negative) in correlation with histology as well as blood samples and adverse clinical symptoms were recorded. Histology revealed pilocytic astrocytoma (n = 7), classical medulloblastoma (n = 4), anaplastic astrocytoma (n = 1), glioblastoma (n = 3) and anaplastic ependymoma (n = 1). Positive fluorescence was observed in cases of anaplastic astrocytoma, glioblastoma, and medulloblastoma, respectively. Significant increases were registered for alanine aminotransferase (14.92 ± 1.106 U/l vs. 37.70 ± 3.795 U/l, P = 0.0020) and gamma glutamyl transpeptidase (12.69 ± 1.638 U/l vs. 39.29 ± 6.342 U/l, P = 0.0156), correlated with young age. No further adverse reactions were evident. Positive fluorescence was observed in two high-grade gliomas and one medulloblastoma after oral administration of 5-ALA. Thus, 5-ALA appears capable of inducing fluorescence in pediatric high-grade tumors. Adverse reactions observed in children were similar to those reported for adults, although very young children might be at increased risk. Further studies are required to elucidate pharmacokinetic and pharmacodynamic properties of 5-ALA in children and to assess its prognostic role in the resection of pediatric brain tumors.

Adult-onset Alexander disease, associated with a mutation in an alternative GFAP transcript, may be phenotypically modulated by a non-neutral HDAC6 variant.

PubMed

Melchionda, Laura; Fang, Mingyan; Wang, Hairong; Fugnanesi, Valeria; Morbin, Michela; Liu, Xuanzhu; Li, Wenyan; Ceccherini, Isabella; Farina, Laura; Savoiardo, Mario; D'Adamo, Pio; Zhang, Jianguo; Costa, Alfredo; Ravaglia, Sabrina; Ghezzi, Daniele; Zeviani, Massimo

2013-05-01

We studied a family including two half-siblings, sharing the same mother, affected by slowly progressive, adult-onset neurological syndromes. In spite of the diversity of the clinical features, characterized by a mild movement disorder with cognitive impairment in the elder patient, and severe motor-neuron disease (MND) in her half-brother, the brain Magnetic Resonance Imaging (MRI) features were compatible with adult-onset Alexander's disease (AOAD), suggesting different expression of the same, genetically determined, condition. Since mutations in the alpha isoform of glial fibrillary acidic protein, GFAP-α, the only cause so far known of AOAD, were excluded, we applied exome Next Generation Sequencing (NGS) to identify gene variants, which were then functionally validated by molecular characterization of recombinant and patient-derived cells. Exome-NGS revealed a mutation in a previously neglected GFAP isoform, GFAP-ϵ, which disrupts the GFAP-associated filamentous cytoskeletal meshwork of astrocytoma cells. To shed light on the different clinical features in the two patients, we sought for variants in other genes. The male patient had a mutation, absent in his half-sister, in X-linked histone deacetylase 6, a candidate MND susceptibility gene. Exome-NGS is an unbiased approach that not only helps identify new disease genes, but may also contribute to elucidate phenotypic expression.

Numerical Evaluation of Lateral Diffusion Inside Diffusive Gradients in Thin Films Samplers

PubMed Central

2015-01-01

Using numerical simulation of diffusion inside diffusive gradients in thin films (DGT) samplers, we show that the effect of lateral diffusion inside the sampler on the solute flux into the sampler is a nonlinear function of the diffusion layer thickness and the physical sampling window size. In contrast, earlier work concluded that this effect was constant irrespective of parameters of the sampler geometry. The flux increase caused by lateral diffusion inside the sampler was determined to be ∼8.8% for standard samplers, which is considerably lower than the previous estimate of ∼20%. Lateral diffusion is also propagated to the diffusive boundary layer (DBL), where it leads to a slightly stronger decrease in the mass uptake than suggested by the common 1D diffusion model that is applied for evaluating DGT results. We introduce a simple correction procedure for lateral diffusion and demonstrate how the effect of lateral diffusion on diffusion in the DBL can be accounted for. These corrections often result in better estimates of the DBL thickness (δ) and the DGT-measured concentration than earlier approaches and will contribute to more accurate concentration measurements in solute monitoring in waters. PMID:25877251

Neuroinflammation, hyperphosphorylated tau, diffuse amyloid plaques, and down-regulation of the cellular prion protein in air pollution exposed children and young adults.

PubMed

Calderón-Garcidueñas, Lilian; Kavanaugh, Michael; Block, Michelle; D'Angiulli, Amedeo; Delgado-Chávez, Ricardo; Torres-Jardón, Ricardo; González-Maciel, Angelica; Reynoso-Robles, Rafael; Osnaya, Norma; Villarreal-Calderon, Rodolfo; Guo, Ruixin; Hua, Zhaowei; Zhu, Hongtu; Perry, George; Diaz, Philippe

2012-01-01

Air pollution exposures have been linked to neuroinflammation and neuropathology. Autopsy samples of the frontal cortex from control (n = 8) and pollution-exposed (n = 35) children and young adults were analyzed by RT-PCR (n = 43) and microarray analysis (n = 12) for gene expression changes in oxidative stress, DNA damage signaling, NFκB signaling, inflammation, and neurodegeneration pathways. The effect of apolipoprotein E (APOE) genotype on the presence of protein aggregates associated with Alzheimer's disease (AD) pathology was also explored. Exposed urbanites displayed differential (>2-fold) regulation of 134 genes. Forty percent exhibited tau hyperphosphorylation with pre-tangle material and 51% had amyloid-β (Aβ) diffuse plaques compared with 0% in controls. APOE4 carriers had greater hyperphosphorylated tau and diffuse Aβ plaques versus E3 carriers (Q = 7.82, p = 0.005). Upregulated gene network clusters included IL1, NFκB, TNF, IFN, and TLRs. A 15-fold frontal down-regulation of the prion-related protein (PrP(C)) was seen in highly exposed subjects. The down-regulation of the PrP(C) is critical given its important roles for neuroprotection, neurodegeneration, and mood disorder states. Elevation of indices of neuroinflammation and oxidative stress, down-regulation of the PrP(C) and AD-associated pathology are present in young megacity residents. The inducible regulation of gene expression suggests they are evolving different mechanisms in an attempt to cope with the constant state of inflammation and oxidative stress related to their environmental exposures. Together, these data support a role for air pollution in CNS damage and its impact upon the developing brain and the potential etiology of AD and mood disorders.

Small-bowel MRI in children and young adults with Crohn disease: retrospective head-to-head comparison of contrast-enhanced and diffusion-weighted MRI.

PubMed

Neubauer, Henning; Pabst, Thomas; Dick, Anke; Machann, Wolfram; Evangelista, Laura; Wirth, Clemens; Köstler, Herbert; Hahn, Dietbert; Beer, Meinrad

2013-01-01

Small-bowel MRI based on contrast-enhanced T1-weighted sequences has been challenged by diffusion-weighted imaging (DWI) for detection of inflammatory bowel lesions and complications in patients with Crohn disease. To evaluate free-breathing DWI, as compared to contrast-enhanced MRI, in children, adolescents and young adults with Crohn disease. This retrospective study included 33 children and young adults with Crohn disease ages 17 ± 3 years (mean ± standard deviation) and 27 matched controls who underwent small-bowel MRI with contrast-enhanced T1-weighted sequences and DWI at 1.5 T. The detectability of Crohn manifestations was determined. Concurrent colonoscopy as reference was available in two-thirds of the children with Crohn disease. DWI and contrast-enhanced MRI correctly identified 32 and 31 patients, respectively. All 22 small-bowel lesions and all Crohn complications were detected. False-positive findings (two on DWI, one on contrast-enhanced MRI), compared to colonoscopy, were a result of large-bowel lumen collapse. Inflammatory wall thickening was comparable on DWI and contrast-enhanced MRI. DWI was superior to contrast-enhanced MRI for detection of lesions in 27% of the assessed bowel segments and equal to contrast-enhanced MRI in 71% of segments. DWI facilitates fast, accurate and comprehensive workup in Crohn disease without the need for intravenous administration of contrast medium. Contrast-enhanced MRI is superior in terms of spatial resolution and multiplanar acquisition.

[What is "normal"? Maternal parenting behavior as risk and protective factor for psychopathology and identity diffusion].

PubMed

Seiffge-Krenke, Inge; Escher, Fabian J

2018-06-01

What is "normal"? Maternal parenting behavior as risk and protective factor for psychopathology and identity diffusion Objectives: This study analyzes the implications of today's highly altered maternal parenting behaviors on children's development and psychological health. The relationship between maternal parenting behaviors (support, psychological control, and anxious monitoring) and delayed identity development or identity diffusion as well as internalizing or externalizing symptomatology was investigated in a sample of 732 youths (301 adolescents, 351 young adults, and 80 patients). Cluster analysis identified two types of maternal parenting behaviors: authoritative maternal behavior and dysfunctionalmaternal behavior. As expected, patients exhibited a high degree of dysfunctional maternal parenting behavior (low support, high psychological control), delayed identity development as well as elevated identity diffusion and symptomatology.Authoritative maternal parenting emerged as a protective factor in the prediction of identity diffusion and symptomatology.All three groups described a high degree of anxious maternal monitoring. The implications of changed maternal parenting behaviors on identity diffusion and symptomatology are discussed in light of societal changes and changing criteria of personality disorders in the new DSM-5.

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

ClinicalTrials.gov

2013-10-07

Childhood High-grade Cerebral Astrocytoma; Childhood Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

Is seborrhoeic dermatitis associated with a diffuse, low-grade folliculitis and progressive cicatricial alopecia?

PubMed

Pitney, Lucy; Weedon, David; Pitney, Michael

2016-08-01

An association between adult scalp seborrhoeic dermatitis and cicatricial hair loss has not previously been convincingly established. This study seeks to demonstrate a unique relationship between a clinically identifiable chronic scalp dermatitis-folliculitis with the characteristic histological features of low-grade inflammatory fibrosing alopecia, resulting in a distinctive progressive cicatricial alopecia which we believe is prevalent and hitherto unrecognised, and befits the description of seborrhoeic folliculitis. The clinical, epidemiological and histopathological features of seborrhoeic folliculitis are demonstrated to establish its unique status among the disorders of adult diffuse cicatricial alopecia. © 2015 The Australasian College of Dermatologists.

SJDAWN: St. Jude Children's Research Hospital Phase 1 Study Evaluating Molecularly-Driven Doublet Therapies for Children and Young Adults With Recurrent Brain Tumors

ClinicalTrials.gov

2018-04-09

Anaplastic Astrocytoma; Anaplastic Ependymoma; Anaplastic Ganglioglioma; Anaplastic Meningioma; Anaplastic Oligodendroglioma; Pleomorphic Xanthoastrocytoma, Anaplastic; Atypical Teratoid/Rhabdoid Tumor; Brain Cancer; Brain Tumor; Central Nervous System Neoplasms; Choroid Plexus Carcinoma; CNS Embryonal Tumor With Rhabdoid Features; Ganglioneuroblastoma of Central Nervous System; CNS Tumor; Embryonal Tumor of CNS; Ependymoma; Glioblastoma; Glioma; Glioma, Malignant; Medulloblastoma; Medulloblastoma; Unspecified Site; Medulloepithelioma; Neuroepithelial Tumor; Neoplasms; Neoplasms, Neuroepithelial; Papillary Tumor of the Pineal Region (High-grade Only); Pediatric Brain Tumor; Pineal Parenchymal Tumor of Intermediate Differentiation (High-grade Only); Pineoblastoma; Primitive Neuroectodermal Tumor; Recurrent Medulloblastoma; Refractory Brain Tumor; Neuroblastoma. CNS; Glioblastoma, IDH-mutant; Glioblastoma, IDH-wildtype; Medulloblastoma, Group 3; Medulloblastoma, Group 4; Glioma, High Grade; Neuroepithelial Tumor, High Grade; Medulloblastoma, SHH-activated and TP53 Mutant; Medulloblastoma, SHH-activated and TP53 Wildtype; Medulloblastoma, Chromosome 9q Loss; Medulloblastoma, Non-WNT Non-SHH, NOS; Medulloblastoma, Non-WNT/Non-SHH; Medulloblastoma, PTCH1 Mutation; Medulloblastoma, WNT-activated; Ependymoma, Recurrent; Glioma, Recurrent High Grade; Glioma, Recurrent Malignant; Embryonal Tumor, NOS; Glioma, Diffuse Midline, H3K27M-mutant; Embryonal Tumor With Multilayered Rosettes (ETMR); Ependymoma, NOS, WHO Grade III; Ependymoma, NOS, WHO Grade II; Medulloblastoma, G3/G4; Ependymoma, RELA Fusion Positive

The diffusion of ecstasy through urban youth networks.

PubMed

Schensul, Jean J; Diamond, Sarah; Disch, William; Bermudez, Rey; Eiserman, Julie

2005-01-01

Ecstasy is a drug commonly associated with all-night, or all-weekend electronic dance events known as raves. Upper- and middle-class clubs, gay bars and clubs, and party venues are other common public settings where ecstasy use occurs. During the mid to late 1990s its use was reported in locations as distant as Australia and New Zealand, England and Scotland, and North America. In the United States, use increased dramatically at the end of the millennium, and drug monitoring systems began to report its presence among urban youth. Using social influence, social marketing and diffusion theory, this paper outlines the micro-level processes through which ecstasy traveled from downtown clubs catering to suburban young adults through urban youth networks through distributors and users. The paper is based on participant observation, and in-depth interviews with dealers and users collected during the period of peak diffusion 1999-2001, and survey data collected from 401 poly-drug users between the ages of 16 and 24 and collected at two time points from 1999-2002.

Hereditary Diffuse Gastric Cancer

MedlinePlus

... Hereditary Diffuse Gastric Cancer Request Permissions Hereditary Diffuse Gastric Cancer Approved by the Cancer.Net Editorial Board , 10/2017 What is hereditary diffuse gastric cancer? Hereditary diffuse gastric cancer (HDGC) is a rare ...

Tract-Specific Analyses of Diffusion Tensor Imaging Show Widespread White Matter Compromise in Autism Spectrum Disorder

ERIC Educational Resources Information Center

Shukla, Dinesh K.; Keehn, Brandon; Muller, Ralph-Axel

2011-01-01

Background: Previous diffusion tensor imaging (DTI) studies have shown white matter compromise in children and adults with autism spectrum disorder (ASD), which may relate to reduced connectivity and impaired function of distributed networks. However, tract-specific evidence remains limited in ASD. We applied tract-based spatial statistics (TBSS)…

Facilitated Diffusion of Transcription Factor Proteins with Anomalous Bulk Diffusion.

PubMed

Liu, Lin; Cherstvy, Andrey G; Metzler, Ralf

2017-02-16

What are the physical laws of the diffusive search of proteins for their specific binding sites on DNA in the presence of the macromolecular crowding in cells? We performed extensive computer simulations to elucidate the protein target search on DNA. The novel feature is the viscoelastic non-Brownian protein bulk diffusion recently observed experimentally. We examine the influence of the protein-DNA binding affinity and the anomalous diffusion exponent on the target search time. In all cases an optimal search time is found. The relative contribution of intermittent three-dimensional bulk diffusion and one-dimensional sliding of proteins along the DNA is quantified. Our results are discussed in the light of recent single molecule tracking experiments, aiming at a better understanding of the influence of anomalous kinetics of proteins on the facilitated diffusion mechanism.

Calibration of diffuse correlation spectroscopy blood flow index with venous-occlusion diffuse optical spectroscopy in skeletal muscle

PubMed Central

Li, Zhe; Baker, Wesley B.; Parthasarathy, Ashwin B.; Ko, Tiffany S.; Wang, Detian; Schenkel, Steven; Durduran, Turgut; Li, Gang; Yodh, Arjun G.

2015-01-01

Abstract. We investigate and assess the utility of a simple scheme for continuous absolute blood flow monitoring based on diffuse correlation spectroscopy (DCS). The scheme calibrates DCS using venous-occlusion diffuse optical spectroscopy (VO-DOS) measurements of arm muscle tissue at a single time-point. A calibration coefficient (γ) for the arm is determined, permitting conversion of DCS blood flow indices to absolute blood flow units, and a study of healthy adults (N=10) is carried out to ascertain the variability of γ. The average DCS calibration coefficient for the right (i.e., dominant) arm was γ=(1.24±0.15)×108 (mL·100  mL−1·min−1)/(cm2/s). However, variability can be significant and is apparent in our site-to-site and day-to-day repeated measurements. The peak hyperemic blood flow overshoot relative to baseline resting flow was also studied following arm-cuff ischemia; excellent agreement between VO-DOS and DCS was found (R2=0.95, slope=0.94±0.07, mean difference=−0.10±0.45). Finally, we show that incorporation of subject-specific absolute optical properties significantly improves blood flow calibration accuracy. PMID:26720870

Anatomy of particle diffusion

NASA Astrophysics Data System (ADS)

Bringuier, E.

2009-11-01

The paper analyses particle diffusion from a thermodynamic standpoint. The main goal of the paper is to highlight the conceptual connection between particle diffusion, which belongs to non-equilibrium statistical physics, and mechanics, which deals with particle motion, at the level of third-year university courses. We start out from the fact that, near equilibrium, particle transport should occur down the gradient of the chemical potential. This yields Fick's law with two additional advantages. First, splitting the chemical potential into 'mechanical' and 'chemical' contributions shows how transport and mechanics are linked through the diffusivity-mobility relationship. Second, splitting the chemical potential into entropic and energetic contributions discloses the respective roles of entropy maximization and energy minimization in driving diffusion. The paper addresses first unary diffusion, where there is only one mobile species in an immobile medium, and next turns to binary diffusion, where two species are mobile with respect to each other in a fluid medium. The interrelationship between unary and binary diffusivities is brought out and it is shown how binary diffusion reduces to unary diffusion in the limit of high dilution of one species amidst the other one. Self- and mutual diffusion are considered and contrasted within the thermodynamic framework; self-diffusion is a time-dependent manifestation of the Gibbs paradox of mixing.

Diffusion of an Evidence-Based Smoking Cessation Intervention Through Facebook: A Randomized Controlled Trial

PubMed Central

Cobb, Nathan K.; Jacobs, Megan A.; Wileyto, Paul; Valente, Thomas

2016-01-01

Objectives. To examine the diffusion of an evidence-based smoking cessation application (“app”) through Facebook social networks and identify specific intervention components that accelerate diffusion. Methods. Between December 2012 and October 2013, we recruited adult US smokers (“seeds”) via Facebook advertising and randomized them to 1 of 12 app variants using a factorial design. App variants targeted components of diffusion: duration of use (t), “contagiousness” (β), and number of contacts (Z). The primary outcome was the reproductive ratio (R), defined as the number of individuals installing the app (“descendants”) divided by the number of a seed participant’s Facebook friends. Results. We randomized 9042 smokers. App utilization metrics demonstrated between-variant differences in expected directions. The highest level of diffusion (R = 0.087) occurred when we combined active contagion strategies with strategies to increase duration of use (incidence rate ratio = 9.99; 95% confidence interval = 5.58, 17.91; P < .001). Involving nonsmokers did not affect diffusion. Conclusions. The maximal R value (0.087) is sufficient to increase the numbers of individuals receiving treatment if applied on a large scale. Online interventions can be designed a priori to spread through social networks. PMID:27077358

Diffusion in silicate melts: III. Empirical models for multicomponent diffusion

NASA Astrophysics Data System (ADS)

Yan, Liang; Richter, Frank M.; Chamberlin, Laurinda

1997-12-01

Empirical models for multicomponent diffusion in an isotropic fluid were derived by splitting the component's dispersion velocity into two parts: (a) an intrinsic velocity which is proportional to each component's electrochemical potential gradient and independent of reference frame and (b) a net interaction velocity which is both model and reference frame dependent. Simple molecules (e.g., M pO q) were chosen as endmember components. The interaction velocity is assumed to be either the same for each component (leading to a common relaxation velocity U) or proportional to a common interaction force ( F). U or F is constrained by requiring no local buildup in either volume or charge. The most general form of the model-derived diffusion matrix [ D] can be written as a product of a model-dependent kinetic matrix [ L] and a model independent thermodynamic matrix [ G], [ D] = [ L] · [ G]. The elements of [ G] are functions of derivatives of chemical potential with respect to concentration. The elements of [ L] are functions of concentration and partial molar volume of the endmember components, Cio and Vio, and self diffusivity Di, and charge number zi of individual diffusing species. When component n is taken as the dependent variable they can be written in a common form L ij = D jδ ij + C io[V noD n - V joD j)A i + (p nz nD n - p jz jD j)B i] where the functional forms of the scaling factors Ai and Bi depend on the model considered. The off-diagonal element Lij ( i ≠ j) is directly proportional to the concentration of component i, and thus negligible when i is a dilute component. The salient feature of kinetic interaction or relaxation is to slow down larger (volume or charge) and faster diffusing components and to speed up smaller (volume or charge) and slower moving species, in order to prevent local volume or charge buildup. Empirical models for multicomponent diffusion were tested in the ternary system CaOAl 2O 3SiO 2 at 1500°C and 1 GPa over a large

Simultaneous MR elastography and diffusion acquisitions: diffusion-MRE (dMRE).

PubMed

Yin, Ziying; Magin, Richard L; Klatt, Dieter

2014-05-01

To present a new technique for concurrent MR elastography (MRE) and diffusion MRI: diffusion-MRE (dMRE). In dMRE, shear wave motion and MR signal decay due to diffusion are encoded into the phase and magnitude components of the MR signal by using a pair of bipolar gradients for both motion-sensitization and diffusion encoding. The pulse sequence timing is adjusted so that the bipolar gradients are sensitive to both coherent and incoherent intravoxel motions. The shape, number, and duration of the gradient lobes can be adjusted to provide flexibility and encoding efficiency. In this proof-of-concept study, dMRE was validated using a tissue phantom composed of a gel bead embedded in a hydrated mixture of agarose and gelatin. The apparent diffusion coefficient (ADC) and shear stiffness measured using dMRE were compared with results obtained from separate, conventional spin-echo (SE) diffusion and SE-MRE acquisitions. The averaged ADC values (n = 3) for selected ROIs in the beads were (1.75 ± 0.16) μm(2) /ms and (1.74 ± 0.16) μm(2) /ms for SE-diffusion and dMRE methods, respectively. The corresponding shear stiffness values in the beads were (2.45 ± 0.23) kPa and (2.42 ± 0.20) kPa. Simultaneous MRE and diffusion acquisition is feasible and can be implemented with no observable interference between the two methods. Copyright © 2014 Wiley Periodicals, Inc.

Decompressive craniectomy in diffuse traumatic brain injury.

PubMed

Cooper, D James; Rosenfeld, Jeffrey V; Murray, Lynnette; Arabi, Yaseen M; Davies, Andrew R; D'Urso, Paul; Kossmann, Thomas; Ponsford, Jennie; Seppelt, Ian; Reilly, Peter; Wolfe, Rory

2011-04-21

It is unclear whether decompressive craniectomy improves the functional outcome in patients with severe traumatic brain injury and refractory raised intracranial pressure. From December 2002 through April 2010, we randomly assigned 155 adults with severe diffuse traumatic brain injury and intracranial hypertension that was refractory to first-tier therapies to undergo either bifrontotemporoparietal decompressive craniectomy or standard care. The original primary outcome was an unfavorable outcome (a composite of death, vegetative state, or severe disability), as evaluated on the Extended Glasgow Outcome Scale 6 months after the injury. The final primary outcome was the score on the Extended Glasgow Outcome Scale at 6 months. Patients in the craniectomy group, as compared with those in the standard-care group, had less time with intracranial pressures above the treatment threshold (P<0.001), fewer interventions for increased intracranial pressure (P<0.02 for all comparisons), and fewer days in the intensive care unit (ICU) (P<0.001). However, patients undergoing craniectomy had worse scores on the Extended Glasgow Outcome Scale than those receiving standard care (odds ratio for a worse score in the craniectomy group, 1.84; 95% confidence interval [CI], 1.05 to 3.24; P=0.03) and a greater risk of an unfavorable outcome (odds ratio, 2.21; 95% CI, 1.14 to 4.26; P=0.02). Rates of death at 6 months were similar in the craniectomy group (19%) and the standard-care group (18%). In adults with severe diffuse traumatic brain injury and refractory intracranial hypertension, early bifrontotemporoparietal decompressive craniectomy decreased intracranial pressure and the length of stay in the ICU but was associated with more unfavorable outcomes. (Funded by the National Health and Medical Research Council of Australia and others; DECRA Australian Clinical Trials Registry number, ACTRN012605000009617.).

Imaging growth and isocitrate dehydrogenase 1 mutation are independent predictors for diffuse low-grade gliomas

PubMed Central

Gozé, Catherine; Blonski, Marie; Le Maistre, Guillaume; Bauchet, Luc; Dezamis, Edouard; Page, Philippe; Varlet, Pascale; Capelle, Laurent; Devaux, Bertrand; Taillandier, Luc; Duffau, Hugues; Pallud, Johan

2014-01-01

Background We explored whether spontaneous imaging tumor growth (estimated by the velocity of diametric expansion) and isocitrate dehydrogenase 1 (IDH1) mutation (estimated by IDH1 immunoexpression) were independent predictors of long-term outcomes of diffuse low-grade gliomas in adults. Methods One hundred thirty-one adult patients with newly diagnosed supratentorial diffuse low-grade gliomas were retrospectively studied. Results Isocitrate dehydrogenase 1 mutations were present in 107 patients. The mean spontaneous velocity of diametric expansion was 5.40 ± 5.46 mm/y. During follow-up (mean, 70 ± 54.7 mo), 56 patients presented a malignant transformation and 23 died. The median malignant progression-free survival and the overall survival were significantly longer in cases of slow velocity of diametric expansion (149 and 198 mo, respectively) than in cases of fast velocity of diametric expansion (46 and 82 mo; P < .001 and P < .001, respectively) and in cases with IDH1 mutation (100 and 198 mo, respectively) than in cases without IDH1 mutation (72 mo and not reached; P = .028 and P = .001, respectively). In multivariate analyses, spontaneous velocity of diametric expansion and IDH1 mutation were independent prognostic factors for malignant progression-free survival (P < .001; hazard ratio, 4.23; 95% CI, 1.81–9.40 and P = .019; hazard ratio, 2.39; 95% CI, 1.19–4.66, respectively) and for overall survival (P < .001; hazard ratio, 26.3; 95% CI, 5.42–185.2 and P = .007; hazard ratio, 17.89; 95% CI, 2.15–200.1, respectively). Conclusions The spontaneous velocity of diametric expansion and IDH1 mutation status are 2 independent prognostic values that should be obtained at the beginning of the management of diffuse low-grade gliomas in adults. PMID:24847087

Cosmic ray diffusion: Report of the Workshop in Cosmic Ray Diffusion Theory

NASA Technical Reports Server (NTRS)

Birmingham, T. J.; Jones, F. C.

1975-01-01

A workshop in cosmic ray diffusion theory was held at Goddard Space Flight Center on May 16-17, 1974. Topics discussed and summarized are: (1) cosmic ray measurements as related to diffusion theory; (2) quasi-linear theory, nonlinear theory, and computer simulation of cosmic ray pitch-angle diffusion; and (3) magnetic field fluctuation measurements as related to diffusion theory.

Diffusion Flame Stabilization

NASA Technical Reports Server (NTRS)

Takahashi, Fumiaki; Katta, V. R.

2006-01-01

Diffusion flames are commonly used for industrial burners in furnaces and flares. Oxygen/fuel burners are usually diffusion burners, primarily for safety reasons, to prevent flashback and explosion in a potentially dangerous system. Furthermore, in most fires, condensed materials pyrolyze, vaporize, and burn in air as diffusion flames. As a result of the interaction of a diffusion flame with burner or condensed-fuel surfaces, a quenched space is formed, thus leaving a diffusion flame edge, which plays an important role in flame holding in combustion systems and fire spread through condensed fuels. Despite a long history of jet diffusion flame studies, lifting/blowoff mechanisms have not yet been fully understood, compared to those of premixed flames. In this study, the structure and stability of diffusion flames of gaseous hydrocarbon fuels in coflowing air at normal earth gravity have been investigated experimentally and computationally. Measurements of the critical mean jet velocity (U(sub jc)) of methane, ethane, or propane at lifting or blowoff were made as a function of the coflowing air velocity (U(sub a)) using a tube burner (i.d.: 2.87 mm). By using a computational fluid dynamics code with 33 species and 112 elementary reaction steps, the internal chemical-kinetic structures of the stabilizing region of methane and propane flames were investigated. A peak reactivity spot, i.e., reaction kernel, is formed in the flame stabilizing region due to back-diffusion of heat and radical species against an oxygen-rich incoming flow, thus holding the trailing diffusion flame. The simulated flame base moved downstream under flow conditions close to the measured stability limit.

Diffusion Flame Stabilization

NASA Technical Reports Server (NTRS)

Takahashi, Fumiaki; Katta, Viswanath R.

2007-01-01

Diffusion flames are commonly used for industrial burners in furnaces and flares. Oxygen/fuel burners are usually diffusion burners, primarily for safety reasons, to prevent flashback and explosion in a potentially dangerous system. Furthermore, in most fires, condensed materials pyrolyze, vaporize, and burn in air as diffusion flames. As a result of the interaction of a diffusion flame with burner or condensed-fuel surfaces, a quenched space is formed, thus leaving a diffusion flame edge, which plays an important role in flame holding in combustion systems and fire spread through condensed fuels. Despite a long history of jet diffusion flame studies, lifting/blowoff mechanisms have not yet been fully understood, compared to those of premixed flames. In this study, the structure and stability of diffusion flames of gaseous hydrocarbon fuels in coflowing air at normal earth gravity have been investigated experimentally and computationally. Measurements of the critical mean jet velocity (U(sub jc)) of methane, ethane, or propane at lifting or blowoff were made as a function of the coflowing air velocity (U(sub a)) using a tube burner (i.d.: 2.87 mm) (Fig. 1, left). By using a computational fluid dynamics code with 33 species and 112 elementary reaction steps, the internal chemical-kinetic structures of the stabilizing region of methane and propane flames were investigated (Fig. 1, right). A peak reactivity spot, i.e., reaction kernel, is formed in the flame stabilizing region due to back-diffusion of heat and radical species against an oxygen-rich incoming flow, thus holding the trailing diffusion flame. The simulated flame base moved downstream under flow conditions close to the measured stability limit.

[Circulating endothelial cells--markers of blood vessel lesions in patients with diffuse liver disease].

PubMed

Dynnik, O B

2006-01-01

The increased level of the circulating endothelial cells (CEC) is in direct dependance with a degree of an endothelial trauma. We defined CEC in blood (cells x 104/L) of 67 adults and children with acute and chronic viral hepatitis (A and B) and healthy volontiars. The author obtained reliable results of increased CEC in all groups consisting of patients with diffuse liver deseases (17,4+/-6,5 and 19,8+/-8,4) in comparison with control groups (3,8+/-1,9 and 3,8+/-1,2) thus CEC can be of practical value as a marker of microvessel lesions of the liver. Endotheliocytemia testifies to be a factor during endothelial trauma in pathogenesis of diffuse liver disease.

Toward real-time diffuse optical tomography: accelerating light propagation modeling employing parallel computing on GPU and CPU

NASA Astrophysics Data System (ADS)

Doulgerakis, Matthaios; Eggebrecht, Adam; Wojtkiewicz, Stanislaw; Culver, Joseph; Dehghani, Hamid

2017-12-01

Parameter recovery in diffuse optical tomography is a computationally expensive algorithm, especially when used for large and complex volumes, as in the case of human brain functional imaging. The modeling of light propagation, also known as the forward problem, is the computational bottleneck of the recovery algorithm, whereby the lack of a real-time solution is impeding practical and clinical applications. The objective of this work is the acceleration of the forward model, within a diffusion approximation-based finite-element modeling framework, employing parallelization to expedite the calculation of light propagation in realistic adult head models. The proposed methodology is applicable for modeling both continuous wave and frequency-domain systems with the results demonstrating a 10-fold speed increase when GPU architectures are available, while maintaining high accuracy. It is shown that, for a very high-resolution finite-element model of the adult human head with ˜600,000 nodes, consisting of heterogeneous layers, light propagation can be calculated at ˜0.25 s/excitation source.

Diffusion Strategy Guide.

ERIC Educational Resources Information Center

McCutcheon, James R.; Sanders, John R.

A methodology is presented for planning and managing the spread of educational innovations. The first portion of the guide develops a theoretical framework for diffusion which summarizes and capitalizes on the latest marketing and on the latest marketing and diffusion research findings. Major stages in the diffusion paradigm discussed include…

Helium diffusion in carbonates

NASA Astrophysics Data System (ADS)

Amidon, W. H.; Cherniak, D. J.; Watson, E. B.; Hobbs, D.

2013-12-01

The abundance and large grain size of carbonate minerals make them a potentially attractive target for 4He thermochronology and 3He cosmogenic dating, although the diffusive properties of helium in carbonates remain poorly understood. This work characterizes helium diffusion in calcite and dolomite to better understand the crystal-chemical factors controlling He transport and retentivity. Slabs of cleaved natural calcite and dolomite, and polished sections of calcite cut parallel or normal to c, were implanted with 3He at 3 MeV with a dose of 5x1015/cm2. Implanted carbonates were heated in 1-atm furnaces, and 3He distributions following diffusion anneals were profiled with Nuclear Reaction Analysis using the reaction 3He(d,p)4He. For 3He transport normal to cleavage surfaces in calcite, we obtain the following Arrhenius relation over the temperature range 78-300°C: Dcalcite = 9.0x10-9exp(-55 × 6 kJ mol-1/RT) m2sec-1. Diffusion in calcite exhibits marked anisotropy, with diffusion parallel to c about two orders of magnitude slower than diffusion normal to cleavage faces. He diffusivities for transport normal to the c-axis are similar in value to those normal to cleavage surfaces. Our findings are broadly consistent with helium diffusivities from step-heating measurements of calcite by Copeland et al. (2007); these bulk degassing data may reflect varying effects of diffusional anisotropy. Helium diffusion normal to cleavage surfaces in dolomite is significantly slower than diffusion in calcite, and has a much higher activation energy for diffusion. For dolomite, we obtain the following Arrhenius relation for He diffusion over the temperature range 150-400°C: Ddolomite = 9.0x10-8exp(-92 × 9 kJ mol-1/RT) m2sec-1. The role of crystallographic structure in influencing these differences among diffusivities was evaluated using the maximum aperture approach of Cherniak and Watson (2011), in which crystallographic structures are sectioned along possible diffusion

Low-, medium- and high-dose steroids with or without aminocaproic acid in adult hematopoietic SCT patients with diffuse alveolar hemorrhage.

PubMed

Rathi, N K; Tanner, A R; Dinh, A; Dong, W; Feng, L; Ensor, J; Wallace, S K; Haque, S A; Rondon, G; Price, K J; Popat, U; Nates, J L

2015-03-01

Diffuse alveolar hemorrhage (DAH) is a poorly understood complication of transplantation carrying a high mortality. Patients commonly deteriorate and require intensive care unit (ICU) admission. Treatment with high-dose steroids and aminocaproic acid (ACA) has been suggested. The current study examined 119 critically ill adult hematopoietic transplant patients treated for DAH. Patients were subdivided into low-, medium- and high-dose steroid groups with or without ACA. All groups had similar baseline characteristics and severity of illness scores. Primary objectives were 30, 60, 100 day, ICU and hospital mortality. Overall mortality (n=119) on day 100 was high at 85%. In the steroids and ACA cohort (n=82), there were no significant differences in 30, 60, 100, day, ICU and hospital mortality between the dosing groups. In the steroids only cohort (n=37), the low-dose steroid group had a lower ICU and hospital mortality (P=0.02). Adjunctive treatment with ACA did not produce differences in outcomes. In the multivariate analysis, medium- and high-dose steroids were associated with a higher ICU mortality (P=0.01) as compared with the low-dose group. Our data suggest that treatment strategies may need to be reanalyzed to avoid potentially unnecessary and potentially harmful therapies.

Diffuser Test

NASA Image and Video Library

2007-09-13

Tests begun at Stennis Space Center's E Complex Sept. 13 evaluated a liquid oxygen lead for engine start performance, part of the A-3 Test Facility Subscale Diffuser Risk Mitigation Project at SSC's E-3 Test Facility. Phase 1 of the subscale diffuser project, completed Sept. 24, was a series of 18 hot-fire tests using a 1,000-pound liquid oxygen and gaseous hydrogen thruster to verify maximum duration and repeatability for steam generation supporting the A-3 Test Stand project. The thruster is a stand-in for NASA's developing J-2X engine, to validate a 6 percent scale version of A-3's exhaust diffuser. Testing the J-2X at altitude conditions requires an enormous diffuser. Engineers will generate nearly 4,600 pounds per second of steam to reduce pressure inside A-3's test cell to simulate altitude conditions. A-3's exhaust diffuser has to be able to withstand regulated pressure, temperatures and the safe discharge of the steam produced during those tests. Before the real thing is built, engineers hope to work out any issues on the miniature version. Phase 2 testing is scheduled to begin this month.

Bilateral Brain Regions Associated with Naming in Older Adults

ERIC Educational Resources Information Center

Obler, Loraine K.; Rykhlevskaia, Elena; Schnyer, David; Clark-Cotton, Manuella R.; Spiro, Avron, III; Hyun, JungMoon; Kim, Dae-Shik; Goral, Mira; Albert, Martin L.

2010-01-01

To determine structural brain correlates of naming abilities in older adults, we tested 24 individuals aged 56-79 on two confrontation-naming tests (the Boston Naming Test (BNT) and the Action Naming Test (ANT)), then collected from these individuals structural Magnetic-Resonance Imaging (MRI) and Diffusion Tensor Imaging (DTI) data. Overall,…

Astrocytoma

MedlinePlus

... Pituitary Tumor PNET Schwannoma 2016 WHO Classification Risk Factors Brain Tumor Facts Brain Tumor Dictionary Webinars Anytime Learning About Us Our Founders Board of Directors Staff Leadership Strategic Plan Financials News Careers Brain Tumor Information Brain Anatomy Brain ...

Diffuse radiation

NASA Technical Reports Server (NTRS)

1981-01-01

A diffuse celestial radiation which is isotropic at least on a course scale were measured from the soft X-ray region to about 150 MeV, at which energy the intensity falls below that of the galactic emission for most galactic latitudes. The spectral shape, the intensity, and the established degree of isotropy of this diffuse radiation already place severe constraints on the possible explanations for this radiation. Among the extragalactic theories, the more promising explanations of the isotropic diffuse emission appear to be radiation from exceptional galaxies from matter antimatter annihilation at the boundaries of superclusters of galaxies of matter and antimatter in baryon symmetric big bang models. Other possible sources for extragalactic diffuse gamma radiation are discussed and include normal galaxies, clusters of galaxies, primordial cosmic rays interacting with intergalactic matter, primordial black holes, and cosmic ray leakage from galaxies.

Phase I study of temozolomide in paediatric patients with advanced cancer. United Kingdom Children's Cancer Study Group.

PubMed Central

Estlin, E. J.; Lashford, L.; Ablett, S.; Price, L.; Gowing, R.; Gholkar, A.; Kohler, J.; Lewis, I. J.; Morland, B.; Pinkerton, C. R.; Stevens, M. C.; Mott, M.; Stevens, R.; Newell, D. R.; Walker, D.; Dicks-Mireaux, C.; McDowell, H.; Reidenberg, P.; Statkevich, P.; Marco, A.; Batra, V.; Dugan, M.; Pearson, A. D.

1998-01-01

A phase I study of temozolomide administered orally once a day, on 5 consecutive days, between 500 and 1200 mg m(-2) per 28-day cycle was performed. Children were stratified according to prior craniospinal irradiation or nitrosourea therapy. Sixteen of 20 patients who had not received prior craniospinal irradiation or nitrosourea therapy were evaluable. Myelosuppression was dose limiting, with Common Toxicity Criteria (CTC) grade 4 thrombocytopenia occurring in one of six patients receiving 1000 mg m(-2) per cycle, and two of four patients treated at 1200 mg m(-2) per cycle. Therefore, the maximum-tolerated dose (MTD) was 1000 mg m(-2) per cycle. The MTD was not defined for children with prior craniospinal irradiation because of poor recruitment. Plasma pharmacokinetic analyses showed temozolomide to be rapidly absorbed and eliminated, with linear increases in peak plasma concentrations and systemic exposure with increasing dose. Responses (CR and PR) were seen in two out of five patients with high-grade astrocytomas, and one patient had stable disease. One of ten patients with diffuse intrinsic brain stem glioma achieved a long-term partial response, and a further two patients had stable disease. Therefore, the dose recommended for phase II studies in patients who have not received prior craniospinal irradiation or nitrosoureas is 1000 mg m(-2) per cycle. Further evaluation in diffuse intrinsic brain stem gliomas and other high-grade astrocytomas is warranted. Images Figure 5 p658-b Figure 6 p659-b PMID:9744506

Effective scattering coefficient of the cerebral spinal fluid in adult head models for diffuse optical imaging

NASA Astrophysics Data System (ADS)

Custo, Anna; Wells, William M., III; Barnett, Alex H.; Hillman, Elizabeth M. C.; Boas, David A.

2006-07-01

An efficient computation of the time-dependent forward solution for photon transport in a head model is a key capability for performing accurate inversion for functional diffuse optical imaging of the brain. The diffusion approximation to photon transport is much faster to simulate than the physically correct radiative transport equation (RTE); however, it is commonly assumed that scattering lengths must be much smaller than all system dimensions and all absorption lengths for the approximation to be accurate. Neither of these conditions is satisfied in the cerebrospinal fluid (CSF). Since line-of-sight distances in the CSF are small, of the order of a few millimeters, we explore the idea that the CSF scattering coefficient may be modeled by any value from zero up to the order of the typical inverse line-of-sight distance, or approximately 0.3 mm-1, without significantly altering the calculated detector signals or the partial path lengths relevant for functional measurements. We demonstrate this in detail by using a Monte Carlo simulation of the RTE in a three-dimensional head model based on clinical magnetic resonance imaging data, with realistic optode geometries. Our findings lead us to expect that the diffusion approximation will be valid even in the presence of the CSF, with consequences for faster solution of the inverse problem.

Probing the impact of axial diffusion on nitric oxide exchange dynamics with heliox.

PubMed

Shin, Hye-Won; Condorelli, Peter; Rose-Gottron, Christine M; Cooper, Dan M; George, Steven C

2004-09-01

Exhaled nitric oxide (NO) is a potential noninvasive index of lung inflammation and is thought to arise from the alveolar and airway regions of the lungs. A two-compartment model has been used to describe NO exchange; however, the model neglects axial diffusion of NO in the gas phase, and recent theoretical studies suggest that this may introduce significant error. We used heliox (80% helium, 20% oxygen) as the insufflating gas to probe the impact of axial diffusion (molecular diffusivity of NO is increased 2.3-fold relative to air) in healthy adults (21-38 yr old, n = 9). Heliox decreased the plateau concentration of exhaled NO by 45% (exhalation flow rate of 50 ml/s). In addition, the total mass of NO exhaled in phase I and II after a 20-s breath hold was reduced by 36%. A single-path trumpet model that considers axial diffusion predicts a 50% increase in the maximum airway flux of NO and a near-zero alveolar concentration (Ca(NO)) and source. Furthermore, when NO elimination is plotted vs. constant exhalation flow rate (range 50-500 ml/s), the slope has been previously interpreted as a nonzero Ca(NO) (range 1-5 ppb); however, the trumpet model predicts a positive slope of 0.4-2.1 ppb despite a zero Ca(NO) because of a diminishing impact of axial diffusion as flow rate increases. We conclude that axial diffusion leads to a significant backdiffusion of NO from the airways to the alveolar region that significantly impacts the partitioning of airway and alveolar contributions to exhaled NO.

Genetic lesions in diffuse large B-cell lymphomas

PubMed Central

Testoni, M.; Zucca, E.; Young, K. H.; Bertoni, F.

2015-01-01

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma in adults, accounting for 35%–40% of all cases. The combination of the anti-CD20 monoclonal antibody rituximab with anthracycline-based combination chemotherapy (R-CHOP, rituximab with cyclophosphamide, doxorubicin, vincristine and prednisone) lead to complete remission in most and can cure more than half of patients with DLBCL. The diversity in clinical presentation, as well as the pathologic and biologic heterogeneity, suggests that DLBCL comprises several disease entities that might ultimately benefit from different therapeutic approaches. In this review, we summarize the current literature focusing on the genetic lesions identified in DLBCL. PMID:25605746

Bivelocity hydrodynamics. Diffuse mass flux vs. diffuse volume flux

NASA Astrophysics Data System (ADS)

Brenner, Howard

2013-02-01

An intimate physical connection exists between a fluid’s mass and its volume, with the density ρ serving as a proportionality factor relating these two extensive thermodynamic properties when the fluid is homogeneous. This linkage has led to the erroneous belief among many researchers that a fluid’s diffusive (dissipative) mass flux and its diffusive volume flux counterpart, both occurring in inhomogeneous fluids undergoing transport are, in fact, synonymous. However, the existence of a truly dissipative mass flux (that is, a mass flux that is physically dissipative) has recently and convincingly been shown to be a physical impossibility [H.C. Öttinger, H. Struchtrup, M. Liu, On the impossibility of a dissipative contribution to the mass flux in hydrodynamics, Phys. Rev. E 80 (2009) 056303], owing, among other things, to its violation of the principle of angular momentum conservation. Unfortunately, as a consequence of the erroneous belief in the equality of the diffuse volume and mass fluxes (sans an algebraic sign), this has led many researchers to wrongly conclude that a diffuse volume flux is equally impossible. As a consequence, owing to the fundamental role played by the diffuse volume flux in the theory of bivelocity hydrodynamics [H. Brenner, Beyond Navier-Stokes, Int. J. Eng. Sci. 54 (2012) 67-98], many researchers have been led to falsely dismiss, without due consideration, the possibility of bivelocity hydrodynamics constituting a potentially viable physical theory, which it is believed to be. The present paper corrects this misconception by using a simple concrete example involving an isothermal rotating rigid-body fluid motion to clearly confirm that whereas a diffuse mass flux is indeed impossible, this fact does not exclude the possible existence of a diffuse volume flux and, concomitantly, the possibility that bivelocity hydrodynamics is indeed a potentially viable branch of fluid mechanics.

Constitutional chromosomal events at 22q11 and 15q26 in a child with a pilocytic astrocytoma of the spinal cord

PubMed Central

2014-01-01

We report on a 9-years-old patient with mild intellectual disability, facial dimorphisms, bilateral semicircular canal dysplasia, periventricular nodular heterotopias, bilateral hippocampal malrotation and abnormal cerebellar foliation, who developed mild motor impairment and gait disorder due to a pilocytic astrocytoma of the spinal cord. Array-CGH analysis revealed two paternal inherited chromosomal events: a 484.3 Kb duplication on chromosome 15q26.3 and a 247 Kb deletion on 22q11.23. Further, a second de novo 1.5 Mb deletion on 22q11.21 occurred. Chromosome 22 at q11.2 and chromosome 15 at q24q26 are considered unstable regions subjected to copy number variations, i.e. structural alterations of genome, mediated by low copy repeat sequences or segmental duplications. The link between some structural CNVs, which compromise fundamental processes controlling DNA stability, and genomic disorders suggest a plausible scenario for cancer predisposition. Evaluation of the genes at the breakpoints cannot account simultaneously for the phenotype and tumour development in this patient. The two paternal inherited CNVs arguably are not pathogenic and do not contribute to the clinical manifestations. Similarly, although the de novo large deletion at 22q11.21 overlaps with the Di George (DGS) critical region and results in haploinsufficiency of genes compromising critical processes for DNA stability, this case lacks several hallmarks of DGS. PMID:24860619

Constitutional chromosomal events at 22q11 and 15q26 in a child with a pilocytic astrocytoma of the spinal cord.

PubMed

Mascelli, Samantha; Severino, Mariasavina; Raso, Alessandro; Nozza, Paolo; Tassano, Elisa; Morana, Giovanni; De Marco, Patrizia; Merello, Elisa; Milanaccio, Claudia; Pavanello, Marco; Rossi, Andrea; Cama, Armando; Garrè, Maria Luisa; Capra, Valeria

2014-01-01

We report on a 9-years-old patient with mild intellectual disability, facial dimorphisms, bilateral semicircular canal dysplasia, periventricular nodular heterotopias, bilateral hippocampal malrotation and abnormal cerebellar foliation, who developed mild motor impairment and gait disorder due to a pilocytic astrocytoma of the spinal cord. Array-CGH analysis revealed two paternal inherited chromosomal events: a 484.3 Kb duplication on chromosome 15q26.3 and a 247 Kb deletion on 22q11.23. Further, a second de novo 1.5 Mb deletion on 22q11.21 occurred. Chromosome 22 at q11.2 and chromosome 15 at q24q26 are considered unstable regions subjected to copy number variations, i.e. structural alterations of genome, mediated by low copy repeat sequences or segmental duplications. The link between some structural CNVs, which compromise fundamental processes controlling DNA stability, and genomic disorders suggest a plausible scenario for cancer predisposition. Evaluation of the genes at the breakpoints cannot account simultaneously for the phenotype and tumour development in this patient. The two paternal inherited CNVs arguably are not pathogenic and do not contribute to the clinical manifestations. Similarly, although the de novo large deletion at 22q11.21 overlaps with the Di George (DGS) critical region and results in haploinsufficiency of genes compromising critical processes for DNA stability, this case lacks several hallmarks of DGS.

Adults with Poor Reading Skills: How Lexical Knowledge Interacts with Scores on Standardized Reading Comprehension Tests

ERIC Educational Resources Information Center

McKoon, Gai; Ratcliff, Roger

2016-01-01

Millions of adults in the United States lack the necessary literacy skills for most living wage jobs. For students from adult learning classes, we used a lexical decision task to measure their knowledge of words and we used a decision-making model (Ratcliff's, 1978, diffusion model) to abstract the mechanisms underlying their performance from…

Diffusion barriers

NASA Technical Reports Server (NTRS)

Nicolet, M. A.

1983-01-01

The choice of the metallic film for the contact to a semiconductor device is discussed. One way to try to stabilize a contact is by interposing a thin film of a material that has low diffusivity for the atoms in question. This thin film application is known as a diffusion barrier. Three types of barriers can be distinguished. The stuffed barrier derives its low atomic diffusivity to impurities that concentrate along the extended defects of a polycrystalline layer. Sacrificial barriers exploit the fact that some (elemental) thin films react in a laterally uniform and reproducible fashion. Sacrificial barriers have the advantage that the point of their failure is predictable. Passive barriers are those most closely approximating an ideal barrier. The most-studied case is that of sputtered TiN films. Stuffed barriers may be viewed as passive barriers whose low diffusivity material extends along the defects of the polycrystalline host.

Central Artery Stiffness, Baroreflex Sensitivity, and Brain White Matter Neuronal Fiber Integrity in Older Adults

PubMed Central

Tarumi, Takashi; de Jong, Daan L.K.; Zhu, David C.; Tseng, Benjamin Y.; Liu, Jie; Hill, Candace; Riley, Jonathan; Womack, Kyle B.; Kerwin, Diana R.; Lu, Hanzhang; Cullum, C. Munro; Zhang, Rong

2015-01-01

Cerebral hypoperfusion elevates the risk of brain white matter (WM) lesions and cognitive impairment. Central artery stiffness impairs baroreflex, which controls systemic arterial perfusion, and may deteriorate neuronal fiber integrity of brain WM. The purpose of this study was to examine the associations among brain WM neuronal fiber integrity, baroreflex sensitivity (BRS), and central artery stiffness in older adults. Fifty-four adults (65±6 years) with normal cognitive function or mild cognitive impairment (MCI) were tested. The neuronal fiber integrity of brain WM was assessed from diffusion metrics acquired by diffusion tensor imaging. BRS was measured in response to acute changes in blood pressure induced by bolus injections of vasoactive drugs. Central artery stiffness was measured by carotid-femoral pulse wave velocity (cfPWV). The WM diffusion metrics including fractional anisotropy (FA) and radial (RD) and axial (AD) diffusivities, BRS, and cfPWV were not different between the control and MCI groups. Thus, the data from both groups were combined for subsequent analyses. Across WM, fiber tracts with decreased FA and increased RD were associated with lower BRS and higher cfPWV, with many of the areas presenting spatial overlap. In particular, the BRS assessed during hypotension was strongly correlated with FA and RD when compared with hypertension. Executive function performance was associated with FA and RD in the areas that correlated with cfPWV and BRS. These findings suggest that baroreflex-mediated control of systemic arterial perfusion, especially during hypotension, may play a crucial role in maintaining neuronal fiber integrity of brain WM in older adults. PMID:25623500

Basic concepts of MR imaging, diffusion MR imaging, and diffusion tensor imaging.

PubMed

de Figueiredo, Eduardo H M S G; Borgonovi, Arthur F N G; Doring, Thomas M

2011-02-01

MR image contrast is based on intrinsic tissue properties and specific pulse sequences and parameter adjustments. A growing number of MRI imaging applications are based on diffusion properties of water. To better understand MRI diffusion-weighted imaging, a brief overview of MR physics is presented in this article followed by physics of the evolving techniques of diffusion MR imaging and diffusion tensor imaging. Copyright © 2011. Published by Elsevier Inc.

Collecting and Storing Blood and Brain Tumor Tissue Samples From Children With Brain Tumors

ClinicalTrials.gov

2017-12-11

Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Newly Diagnosed Childhood Ependymoma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma

First-principles multiple-barrier diffusion theory. The case study of interstitial diffusion in CdTe

DOE PAGES

Yang, Ji -Hui; Park, Ji -Sang; Kang, Joongoo; ...

2015-02-17

The diffusion of particles in solid-state materials generally involves several sequential thermal-activation processes. However, presently, diffusion coefficient theory only deals with a single barrier, i.e., it lacks an accurate description to deal with multiple-barrier diffusion. Here, we develop a general diffusion coefficient theory for multiple-barrier diffusion. Using our diffusion theory and first-principles calculated hopping rates for each barrier, we calculate the diffusion coefficients of Cd, Cu, Te, and Cl interstitials in CdTe for their full multiple-barrier diffusion pathways. As a result, we found that the calculated diffusivity agrees well with the experimental measurement, thus justifying our theory, which is generalmore » for many other systems.« less

Adult Literacy Benefits? New Opportunities for Research into Sustainable Development

ERIC Educational Resources Information Center

Post, David

2016-01-01

Understandings of "literacy" broadened after the United Nations Development Decade of the 1960s. The corresponding research into the benefits of literacy also widened its focus beyond economic growth. The effects of adult literacy and its correlates appeared diffuse with the rise of New Literacy Studies, and the scholarship on…

Incomplete initial nutation diffusion imaging: An ultrafast, single-scan approach for diffusion mapping.

PubMed

Ianuş, Andrada; Shemesh, Noam

2018-04-01

Diffusion MRI is confounded by the need to acquire at least two images separated by a repetition time, thereby thwarting the detection of rapid dynamic microstructural changes. The issue is exacerbated when diffusivity variations are accompanied by rapid changes in T 2 . The purpose of the present study is to accelerate diffusion MRI acquisitions such that both reference and diffusion-weighted images necessary for quantitative diffusivity mapping are acquired in a single-shot experiment. A general methodology termed incomplete initial nutation diffusion imaging (INDI), capturing two diffusion contrasts in a single shot, is presented. This methodology creates a longitudinal magnetization reservoir that facilitates the successive acquisition of two images separated by only a few milliseconds. The theory behind INDI is presented, followed by proof-of-concept studies in water phantom, ex vivo, and in vivo experiments at 16.4 and 9.4 T. Mean diffusivities extracted from INDI were comparable with diffusion tensor imaging and the two-shot isotropic diffusion encoding in the water phantom. In ex vivo mouse brain tissues, as well as in the in vivo mouse brain, mean diffusivities extracted from conventional isotropic diffusion encoding and INDI were in excellent agreement. Simulations for signal-to-noise considerations identified the regimes in which INDI is most beneficial. The INDI method accelerates diffusion MRI acquisition to single-shot mode, which can be of great importance for mapping dynamic microstructural properties in vivo without T 2 bias. Magn Reson Med 79:2198-2204, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2017 The Authors Magnetic

Transdermal diffusion of xenon in vitro using diffusion cells

NASA Astrophysics Data System (ADS)

Verkhovsky, A.; Petrov, E.

2015-11-01

The aim of this research was to study the diffusion rate of xenon through guinea pig skin and how viscosity of cosmetic component capryl/capric triglyceride (CCT) facilitates to deliver xenon to surface of skin patches. They were placed in Franz cell for 24 hours and diffusion rate and permeability of xenon were calculated. Thus diffusion rate was 0.031 mg/hour*cm2 and permeability was 0.003 cm/hour. Using Brookfield viscometer it was shown that viscosity of CCT decreased upon increasing xenon concentration. Obtained results can be utilized in developing of new xenon containing drugs for topical administration.

NIST Diffusion Data Center

National Institute of Standards and Technology Data Gateway

NIST Diffusion Data Center (Web, free access)   The NIST Diffusion Data Center is a collection of over 14,100 international papers, theses, and government reports on diffusion published before 1980.

Real Diffusion-Weighted MRI Enabling True Signal Averaging and Increased Diffusion Contrast

PubMed Central

Eichner, Cornelius; Cauley, Stephen F; Cohen-Adad, Julien; Möller, Harald E; Turner, Robert; Setsompop, Kawin; Wald, Lawrence L

2015-01-01

This project aims to characterize the impact of underlying noise distributions on diffusion-weighted imaging. The noise floor is a well-known problem for traditional magnitude-based diffusion-weighted MRI (dMRI) data, leading to biased diffusion model fits and inaccurate signal averaging. Here, we introduce a total-variation-based algorithm to eliminate shot-to-shot phase variations of complex-valued diffusion data with the intention to extract real-valued dMRI datasets. The obtained real-valued diffusion data are no longer superimposed by a noise floor but instead by a zero-mean Gaussian noise distribution, yielding dMRI data without signal bias. We acquired high-resolution dMRI data with strong diffusion weighting and, thus, low signal-to-noise ratio. Both the extracted real-valued and traditional magnitude data were compared regarding signal averaging, diffusion model fitting and accuracy in resolving crossing fibers. Our results clearly indicate that real-valued diffusion data enables idealized conditions for signal averaging. Furthermore, the proposed method enables unbiased use of widely employed linear least squares estimators for model fitting and demonstrates an increased sensitivity to detect secondary fiber directions with reduced angular error. The use of phase-corrected, real-valued data for dMRI will therefore help to clear the way for more detailed and accurate studies of white matter microstructure and structural connectivity on a fine scale. PMID:26241680

Diffuse Gamma Rays Galactic and Extragalactic Diffuse Emission

NASA Technical Reports Server (NTRS)

Moskalenko, Igor V.; Strong, Andrew W.; Reimer, Olaf

2004-01-01

Diffuse gamma rays consist of several components: truly diffuse emission from the interstellar medium, the extragalactic background, whose origin is not firmly established yet, and the contribution from unresolved and faint Galactic point sources. One approach to unravel these components is to study the diffuse emission from the interstellar medium, which traces the interactions of high energy particles with interstellar gas and radiation fields. Because of its origin such emission is potentially able to reveal much about the sources and propagation of cosmic rays. The extragalactic background, if reliably determined, can be used in cosmological and blazar studies. Studying the derived average spectrum of faint Galactic sources may be able to give a clue to the nature of the emitting objects.

Turing instability in reaction-diffusion systems with nonlinear diffusion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zemskov, E. P., E-mail: zemskov@ccas.ru

2013-10-15

The Turing instability is studied in two-component reaction-diffusion systems with nonlinear diffusion terms, and the regions in parametric space where Turing patterns can form are determined. The boundaries between super- and subcritical bifurcations are found. Calculations are performed for one-dimensional brusselator and oregonator models.

Helium Diffusion in Olivine

NASA Astrophysics Data System (ADS)

Cherniak, D. J.; Watson, E. B.

2011-12-01

Diffusion of helium has been characterized in natural Fe-bearing olivine (~Fo90) and synthetic forsterite. Polished, oriented slabs of olivine were implanted with 3He, at 100 keV at a dose of 5x1015/cm2 or at 3.0 MeV at a dose of 1x1016/cm2. A set of experiments on the implanted olivine were run in 1-atm furnaces. In addition to the one-atm experiments, experiments on implanted samples were also run at higher pressures (2.6 and 2.7 GPa) to assess the potential effects of pressure on He diffusion and the applicability of the measured diffusivities in describing He transport in the mantle. The high-pressure experiments were conducted in a piston-cylinder apparatus using an "ultra-soft" pressure cell, with the diffusion sample directly surrounded by AgCl. 3He distributions following experiments were measured with Nuclear Reaction Analysis using the reaction 3He(d,p)4He. This direct profiling method permits us to evaluate anisotropy of diffusion, which cannot be easily assessed using bulk-release methods. For diffusion in forsterite parallel to c we obtain the following Arrhenius relation over the temperatures 250-950°C: D = 3.91x10-6exp(-159 ± 4 kJ mol-1/RT) m2/sec. The data define a single Arrhenius line spanning more than 7 orders of magnitude in D and 700°C in temperature. Diffusion parallel to a appears slightly slower, yielding an activation energy for diffusion of 135 kJ/mol and a pre-exponential factor of 3.73x10-8 m2/sec. Diffusion parallel to b is slower than diffusion parallel to a (by about two-thirds of a log unit); for this orientation an activation energy of 138 kJ/mol and a pre-exponential factor of 1.34x10-8 m2/sec are obtained. This anisotropy is broadly consistent with observations for diffusion of Ni and Fe-Mg in olivine. Diffusion in Fe-bearing olivine (transport parallel to b) agrees within uncertainty with findings for He diffusion in forsterite. The higher-pressure experiments yield diffusivities in agreement with those from the 1-atm

Enhancing Cation Diffusion and Suppressing Anion Diffusion via Lewis-Acidic Polymer Electrolytes.

PubMed

Savoie, Brett M; Webb, Michael A; Miller, Thomas F

2017-02-02

Solid polymer electrolytes (SPEs) have the potential to increase both the energy density and stability of lithium-based batteries, but low Li + conductivity remains a barrier to technological viability. SPEs are designed to maximize Li + diffusivity relative to the anion while maintaining sufficient salt solubility. It is thus remarkable that poly(ethylene oxide) (PEO), the most widely used SPE, exhibits Li + diffusivity that is an order of magnitude smaller than that of typical counterions at moderate salt concentrations. We show that Lewis-basic polymers like PEO favor slow cation and rapid anion diffusion, while this relationship can be reversed in Lewis-acidic polymers. Using molecular dynamics, polyboranes are identified that achieve up to 10-fold increases in Li + diffusivities and significant decreases in anion diffusivities, relative to PEO in the dilute-ion regime. These results illustrate a general principle for increasing Li + diffusivity and transference number with chemistries that exhibit weaker cation and stronger anion coordination.

Reduction of Diffusion-Weighted Imaging Contrast of Acute Ischemic Stroke at Short Diffusion Times.

PubMed

Baron, Corey Allan; Kate, Mahesh; Gioia, Laura; Butcher, Kenneth; Emery, Derek; Budde, Matthew; Beaulieu, Christian

2015-08-01

Diffusion-weighted imaging (DWI) of tissue water is a sensitive and specific indicator of acute brain ischemia, where reductions of the diffusion of tissue water are observed acutely in the stroke lesion core. Although these diffusion changes have been long attributed to cell swelling, the precise nature of the biophysical mechanisms remains uncertain. The potential cause of diffusion reductions after stroke was investigated using an advanced DWI technique, oscillating gradient spin-echo DWI, that enables much shorter diffusion times and can improve specificity for alterations of structure at the micron level. Diffusion measurements in the white matter lesions of patients with acute ischemic stroke were reduced by only 8% using oscillating gradient spin-echo DWI, in contrast to a 37% decrease using standard DWI. Neurite beading has recently been proposed as a mechanism for the diffusion changes after ischemic stroke with some ex vivo evidence. To explore whether beading could cause such differential results, simulations of beaded cylinders and axonal swelling were performed, yielding good agreement with experiment. Short diffusion times result in dramatically reduced diffusion contrast of human stroke. Simulations implicate a combination of neuronal beading and axonal swelling as the key structural changes leading to the reduced apparent diffusion coefficient after stroke. © 2015 American Heart Association, Inc.

Trace element diffusion in minerals: the role of multiple diffusion mechanisms operating simultaneously

NASA Astrophysics Data System (ADS)

Dohmen, R.; Marschall, H.; Wiedenbeck, M.; Polednia, J.; Chakraborty, S.

2016-12-01

Diffusion of trace elements, often with ionic charge that differs from those of ions in the regular structural sites of a mineral, controls a number of important processes in rocks, such as: (i) Closure of radiogenic isotopic systems, (e.g. Pb diffusion in rutile; REE diffusion in garnet); (ii) Closure of trace element thermometers (e.g., Zr in rutile, Mg in plagioclase, Al in olivine); (iii) Closure of element exchange between melt inclusions and host minerals (e.g., H, REE in olivine). In addition, preserved trace element zoning profiles in minerals can be used for diffusion chronometry (e.g. Nb in rutile, Mg in plagioclase). However, experimentally determined diffusion coefficients of these trace elements are in many cases controversial (e.g., REE in olivine: [1] vs. [2]; Mg in plagioclase: [3] vs. [4]). We have carried out experiments to study the diffusion behavior in olivine, rutile, and plagioclase, and are able to show that two mechanisms of diffusion, differing in rates by up to four orders of magnitude, may operate simultaneously in a given crystal. The two mechanisms result in complex diffusion profile shapes. As a general rule, the incorporation of heterovalent substituting elements in relatively high concentrations is necessary to activate two diffusion mechanisms. This behavior is produced by the control of these elements on the point defect chemistry of a mineral - these impurities become a majority point defect when a threshold concentration limit is exceeded. In certain cases, e.g., for Li in olivine, the trace element can also be incorporated in different sites, resulting in interaction of the different species with other point defects (vacancies) during diffusion. Thus, depending on the diffusion couple used in the experiment, the associated concentration gradients within the mineral, and the analytical techniques used to measure the diffusion profile, only one diffusion mechanism may be activated or detected. These studies allow us to explain

Nonmonotonic diffusion in crowded environments

PubMed Central

Putzel, Gregory Garbès; Tagliazucchi, Mario; Szleifer, Igal

2015-01-01

We study the diffusive motion of particles among fixed spherical crowders. The diffusers interact with the crowders through a combination of a hard-core repulsion and a short-range attraction. The long-time effective diffusion coefficient of the diffusers is found to depend non-monotonically on the strength of their attraction to the crowders. That is, for a given concentration of crowders, a weak attraction to the crowders enhances diffusion. We show that this counterintuitive fact can be understood in terms of the mesoscopic excess chemical potential landscape experienced by the diffuser. The roughness of this excess chemical potential landscape quantitatively captures the nonmonotonic dependence of the diffusion rate on the strength of crowder-diffuser attraction; thus it is a purely static predictor of dynamic behavior. The mesoscopic view given here provides a unified explanation for enhanced diffusion effects that have been found in various systems of technological and biological interest. PMID:25302920

Moist, Double-diffusive convection

NASA Astrophysics Data System (ADS)

Oishi, Jeffrey; Burns, Keaton; Brown, Ben; Lecoanet, Daniel; Vasil, Geoffrey

2017-11-01

Double-diffusive convection occurs when the competition between stabilizing and a destabilizing buoyancy source is mediated by a difference in the diffusivity of each source. Such convection is important in a wide variety of astrophysical and geophysical flows. However, in giant planets, double-diffusive convection occurs in regions where condensation of important components of the atmosphere occurs. Here, we present preliminary calculations of moist, double-diffusive convection using the Dedalus pseudospectral framework. Using a simple model for phase change, we verify growth rates for moist double diffusive convection from linear calculations and report on preliminary relationships between the ability to form liquid phase and the resulting Nusselt number in nonlinear simulations.

Parallel flow diffusion battery

DOEpatents

Yeh, H.C.; Cheng, Y.S.

1984-01-01

A parallel flow diffusion battery for determining the mass distribution of an aerosol has a plurality of diffusion cells mounted in parallel to an aerosol stream, each diffusion cell including a stack of mesh wire screens of different density.

Parallel flow diffusion battery

DOEpatents

Yeh, Hsu-Chi; Cheng, Yung-Sung

1984-08-07

A parallel flow diffusion battery for determining the mass distribution of an aerosol has a plurality of diffusion cells mounted in parallel to an aerosol stream, each diffusion cell including a stack of mesh wire screens of different density.

Diffusion bonding aeroengine components

NASA Astrophysics Data System (ADS)

Fitzpatrick, G. A.; Broughton, T.

1988-10-01

The use of diffusion bonding processes at Rolls-Royce for the manufacture of titanium-alloy aircraft engine components and structures is described. A liquid-phase diffusion bonding process called activated diffusion bonding has been developed for the manufacture of the hollow titanium wide chord fan blade. In addition, solid-state diffusion bonding is being used in the manufacture of hollow vane/blade airfoil constructions mainly in conjunction with superplastic forming and hot forming techniques.

Diffusion of Small Solute Particles in Viscous Liquids: Cage Diffusion, a Result of Decoupling of Solute-Solvent Dynamics, Leads to Amplification of Solute Diffusion.

PubMed

Acharya, Sayantan; Nandi, Manoj K; Mandal, Arkajit; Sarkar, Sucharita; Bhattacharyya, Sarika Maitra

2015-08-27

We study the diffusion of small solute particles through solvent by keeping the solute-solvent interaction repulsive and varying the solvent properties. The study involves computer simulations, development of a new model to describe diffusion of small solutes in a solvent, and also mode coupling theory (MCT) calculations. In a viscous solvent, a small solute diffuses via coupling to the solvent hydrodynamic modes and also through the transient cages formed by the solvent. The model developed can estimate the independent contributions from these two different channels of diffusion. Although the solute diffusion in all the systems shows an amplification, the degree of it increases with solvent viscosity. The model correctly predicts that when the solvent viscosity is high, the solute primarily diffuses by exploiting the solvent cages. In such a scenario the MCT diffusion performed for a static solvent provides a correct estimation of the cage diffusion.

Patterns of diagnostic marker assessment in adult diffuse glioma: a survey of the European Confederation of Neuropathological Societies (Euro-CNS)

PubMed Central

Woehrer, Adelheid; Kristensen, Bjarne W.; Vital, Anne; Hainfellner, Johannes A.

2017-01-01

The 2016 update of the WHO classification has introduced an integrated diagnostic approach that incorporates both tumor morphology and molecular information. This conceptual change has far-reaching implications, especially for neuropathologists who are in the forefront of translating molecular markers to routine diagnostic use. Adult diffuse glioma is a prototypic example for a group of tumors that underwent substantial regrouping, and it represents a major workload for surgical neuropathologists. Hence, we conducted a survey among members of the European Confederation of Neuropathological Societies (Euro-CNS) in order to assess 1) the extent to which molecular markers have already been incorporated in glioma diagnoses, 2) which molecular techniques are in daily use, and 3) to set a baseline for future surveys in this field. Based on 130 responses from participants across 40 nations neuropathologists uniformly rate molecular marker testing as highly relevant and already incorporate molecular information in their diagnostic assessments. At the same time however, the survey documents substantial differences in access to crucial biomarkers and molecular techniques across geographic regions and within individual countries. Concerns are raised concerning the validity of test assays with MGMT, 1p19q, and ATRX; being perceived as most problematic. Neuropathologists advocate the need for international harmonization of standards and consensus guidelines, and the majority is willing to actively engage in interlaboratory trials aiming at quality control (Figure 1). PMID:27966427

Sucrose diffusion in aqueous solution

PubMed Central

Murray, Benjamin J.

2016-01-01

The diffusion of sugar in aqueous solution is important both in nature and in technological applications, yet measurements of diffusion coefficients at low water content are scarce. We report directly measured sucrose diffusion coefficients in aqueous solution. Our technique utilises a Raman isotope tracer method to monitor the diffusion of non-deuterated and deuterated sucrose across a boundary between the two aqueous solutions. At a water activity of 0.4 (equivalent to 90 wt% sucrose) at room temperature, the diffusion coefficient of sucrose was determined to be approximately four orders of magnitude smaller than that of water in the same material. Using literature viscosity data, we show that, although inappropriate for the prediction of water diffusion, the Stokes–Einstein equation works well for predicting sucrose diffusion under the conditions studied. As well as providing information of importance to the fundamental understanding of diffusion in binary solutions, these data have technological, pharmaceutical and medical implications, for example in cryopreservation. Moreover, in the atmosphere, slow organic diffusion may have important implications for aerosol growth, chemistry and evaporation, where processes may be limited by the inability of a molecule to diffuse between the bulk and the surface of a particle. PMID:27364512

Quiet echo planar imaging for functional and diffusion MRI

PubMed Central

Price, Anthony N.; Cordero‐Grande, Lucilio; Malik, Shaihan; Ferrazzi, Giulio; Gaspar, Andreia; Hughes, Emer J.; Christiaens, Daan; McCabe, Laura; Schneider, Torben; Rutherford, Mary A.; Hajnal, Joseph V.

2017-01-01

Purpose To develop a purpose‐built quiet echo planar imaging capability for fetal functional and diffusion scans, for which acoustic considerations often compromise efficiency and resolution as well as angular/temporal coverage. Methods The gradient waveforms in multiband‐accelerated single‐shot echo planar imaging sequences have been redesigned to minimize spectral content. This includes a sinusoidal read‐out with a single fundamental frequency, a constant phase encoding gradient, overlapping smoothed CAIPIRINHA blips, and a novel strategy to merge the crushers in diffusion MRI. These changes are then tuned in conjunction with the gradient system frequency response function. Results Maintained image quality, SNR, and quantitative diffusion values while reducing acoustic noise up to 12 dB (A) is illustrated in two adult experiments. Fetal experiments in 10 subjects covering a range of parameters depict the adaptability and increased efficiency of quiet echo planar imaging. Conclusion Purpose‐built for highly efficient multiband fetal echo planar imaging studies, the presented framework reduces acoustic noise for all echo planar imaging‐based sequences. Full optimization by tuning to the gradient frequency response functions allows for a maximally time‐efficient scan within safe limits. This allows ambitious in‐utero studies such as functional brain imaging with high spatial/temporal resolution and diffusion scans with high angular/spatial resolution to be run in a highly efficient manner at acceptable sound levels. Magn Reson Med 79:1447–1459, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. PMID:28653363

Converting Multi-Shell and Diffusion Spectrum Imaging to High Angular Resolution Diffusion Imaging

PubMed Central

Yeh, Fang-Cheng; Verstynen, Timothy D.

2016-01-01

Multi-shell and diffusion spectrum imaging (DSI) are becoming increasingly popular methods of acquiring diffusion MRI data in a research context. However, single-shell acquisitions, such as diffusion tensor imaging (DTI) and high angular resolution diffusion imaging (HARDI), still remain the most common acquisition schemes in practice. Here we tested whether multi-shell and DSI data have conversion flexibility to be interpolated into corresponding HARDI data. We acquired multi-shell and DSI data on both a phantom and in vivo human tissue and converted them to HARDI. The correlation and difference between their diffusion signals, anisotropy values, diffusivity measurements, fiber orientations, connectivity matrices, and network measures were examined. Our analysis result showed that the diffusion signals, anisotropy, diffusivity, and connectivity matrix of the HARDI converted from multi-shell and DSI were highly correlated with those of the HARDI acquired on the MR scanner, with correlation coefficients around 0.8~0.9. The average angular error between converted and original HARDI was 20.7° at voxels with signal-to-noise ratios greater than 5. The network topology measures had less than 2% difference, whereas the average nodal measures had a percentage difference around 4~7%. In general, multi-shell and DSI acquisitions can be converted to their corresponding single-shell HARDI with high fidelity. This supports multi-shell and DSI acquisitions over HARDI acquisition as the scheme of choice for diffusion acquisitions. PMID:27683539

Toward real-time diffuse optical tomography: accelerating light propagation modeling employing parallel computing on GPU and CPU.

PubMed

Doulgerakis, Matthaios; Eggebrecht, Adam; Wojtkiewicz, Stanislaw; Culver, Joseph; Dehghani, Hamid

2017-12-01

Parameter recovery in diffuse optical tomography is a computationally expensive algorithm, especially when used for large and complex volumes, as in the case of human brain functional imaging. The modeling of light propagation, also known as the forward problem, is the computational bottleneck of the recovery algorithm, whereby the lack of a real-time solution is impeding practical and clinical applications. The objective of this work is the acceleration of the forward model, within a diffusion approximation-based finite-element modeling framework, employing parallelization to expedite the calculation of light propagation in realistic adult head models. The proposed methodology is applicable for modeling both continuous wave and frequency-domain systems with the results demonstrating a 10-fold speed increase when GPU architectures are available, while maintaining high accuracy. It is shown that, for a very high-resolution finite-element model of the adult human head with ∼600,000 nodes, consisting of heterogeneous layers, light propagation can be calculated at ∼0.25  s/excitation source. (2017) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).

Oxygen diffusion in monazite

NASA Astrophysics Data System (ADS)

Cherniak, D. J.; Zhang, X. Y.; Nakamura, M.; Watson, E. B.

2004-09-01

We report measurements of oxygen diffusion in natural monazites under both dry, 1-atm conditions and hydrothermal conditions. For dry experiments, 18O-enriched CePO4 powder and monazite crystals were sealed in Ag-Pd capsules with a solid buffer (to buffer at NNO) and annealed in 1-atm furnaces. Hydrothermal runs were conducted in cold-seal pressure vessels, where monazite grains were encapsulated with 18O-enriched water. Following the diffusion anneals, oxygen concentration profiles were measured with Nuclear Reaction Analysis (NRA) using the reaction 18O(p,α)15N. Over the temperature range 850-1100 °C, the Arrhenius relation determined for dry diffusion experiments on monazite is given by: Under wet conditions at 100 MPa water pressure, over the temperature range 700-880 °C, oxygen diffusion can be described by the Arrhenius relationship: Oxygen diffusion under hydrothermal conditions has a significantly lower activation energy for diffusion than under dry conditions, as has been found the case for many other minerals, both silicate and nonsilicate. Given these differences in activation energies, the differences between dry and wet diffusion rates increase with lower temperatures; for example, at 600 °C, dry diffusion will be more than 4 orders of magnitude slower than diffusion under hydrothermal conditions. These disparate diffusivities will result in pronounced differences in the degree of retentivity of oxygen isotope signatures. For instance, under dry conditions (presumably rare in the crust) and high lower-crustal temperatures (∼800 °C), monazite cores of 70-μm radii will preserve O isotope ratios for about 500,000 years; by comparison, they would be retained at this temperature under wet conditions for about 15,000 years.

Diffusion-weighted MRI derived apparent diffusion coefficient identifies prognostically distinct subgroups of pediatric diffuse intrinsic pontine glioma.

PubMed

Lober, Robert M; Cho, Yoon-Jae; Tang, Yujie; Barnes, Patrick D; Edwards, Michael S; Vogel, Hannes; Fisher, Paul G; Monje, Michelle; Yeom, Kristen W

2014-03-01

While pediatric diffuse intrinsic pontine gliomas (DIPG) remain fatal, recent data have shown subgroups with distinct molecular biology and clinical behavior. We hypothesized that diffusion-weighted MRI can be used as a prognostic marker to stratify DIPG subsets with distinct clinical behavior. Apparent diffusion coefficient (ADC) values derived from diffusion-weighted MRI were computed in 20 consecutive children with treatment-naïve DIPG tumors. The median ADC for the cohort was used to stratify the tumors into low and high ADC groups. Survival, gender, therapy, and potential steroid effects were compared between the ADC groups. Median age at diagnosis was 6.6 (range 2.3-13.2) years, with median follow-up seven (range 1-36) months. There were 14 boys and six girls. Seventeen patients received radiotherapy, five received chemotherapy, and six underwent cerebrospinal fluid diversion. The median ADC of 1,295 × 10(-6) mm(2)/s for the cohort partitioned tumors into low or high diffusion groups, which had distinct median survivals of 3 and 13 months, respectively (log-rank p < 0.001). Low ADC tumors were found only in boys, whereas high ADC tumors were found in both boys and girls. Available tissue specimens in three low ADC tumors demonstrated high-grade histology, whereas one high ADC tumor demonstrated low-grade histology with a histone H3.1 K27M mutation and high-grade metastatic lesion at autopsy. ADC derived from diffusion-weighted MRI may identify prognostically distinct subgroups of pediatric DIPG.

Anomalous diffusion of brain metabolites evidenced by diffusion-weighted magnetic resonance spectroscopy in vivo

PubMed Central

Marchadour, Charlotte; Brouillet, Emmanuel; Hantraye, Philippe; Lebon, Vincent; Valette, Julien

2012-01-01

Translational displacement of molecules within cells is a key process in cellular biology. Molecular motion potentially depends on many factors, including active transport, cytosol viscosity and molecular crowding, tortuosity resulting from cytoskeleton and organelles, and restriction barriers. However, the relative contribution of these factors to molecular motion in the cytoplasm remains poorly understood. In this work, we designed an original diffusion-weighted magnetic resonance spectroscopy strategy to probe molecular motion at subcellular scales in vivo. This led to the first observation of anomalous diffusion, that is, dependence of the apparent diffusion coefficient (ADC) on the diffusion time, for endogenous intracellular metabolites in the brain. The observed increase of the ADC at short diffusion time yields evidence that metabolite motion is characteristic of hindered random diffusion rather than active transport, for time scales up to the dozen milliseconds. Armed with this knowledge, data modeling based on geometrically constrained diffusion was performed. Results suggest that metabolite diffusion occurs in a low-viscosity cytosol hindered by ∼2-μm structures, which is consistent with known intracellular organization. PMID:22929443

Diffusion in Jammed Particle Packs.

PubMed

Bolintineanu, Dan S; Grest, Gary S; Lechman, Jeremy B; Silbert, Leonardo E

2015-08-21

Using random walk simulations we explore diffusive transport through monodisperse sphere packings over a range of packing fractions ϕ in the vicinity of the jamming transition at ϕ(c). Various diffusion properties are computed over several orders of magnitude in both time and packing pressure. Two well-separated regimes of normal "Fickian" diffusion, where the mean squared displacement is linear in time, are observed. The first corresponds to diffusion inside individual spheres, while the latter is the long-time bulk diffusion. The intermediate anomalous diffusion regime and the long-time value of the diffusion coefficient are both shown to be controlled by particle contacts, which in turn depend on proximity to ϕ(c). The time required to recover normal diffusion t* scales as (ϕ-ϕ(c))(-0.5) and the long-time diffusivity D(∞)∼(ϕ-ϕ(c))0.5, or D(∞)∼1/t*. It is shown that the distribution of mean first passage times associated with the escape of random walkers between neighboring particles controls both t* and D(∞) in the limit ϕ→ϕ(c).

Lung diffusion testing

MedlinePlus

... page: //medlineplus.gov/ency/article/003854.htm Lung diffusion testing To use the sharing features on this page, please enable JavaScript. Lung diffusion testing measures how well the lungs exchange gases. ...

General Model of Hindered Diffusion.

PubMed

Eloul, Shaltiel; Compton, Richard G

2016-11-03

The diffusion of a particle from bulk solution is slowed as it moves close to an adsorbing surface. A general model is reported that is easily applied by theoreticians and experimentalists. Specifically, it is shown here that in general and regardless of the space size, the magnitude of the effect of hindered diffusion on the flux is a property of the diffusion layer thickness. We explain and approximate the effect. Predictions of concentration profiles show that a "hindered diffusion layer" is formed near the adsorbing surface within the diffusion layer, observed even when the particle radius is just a 0.1% of the diffusion layer thickness. In particular, we focus on modern electrochemistry processes involving with impact of particles with either ultrasmall electrodes or particles in convective systems. The concept of the "hindered diffusion layer" is generally important for example in recent biophysical models of particles diffusion to small targets.

A monte carlo study of restricted diffusion: Implications for diffusion MRI of prostate cancer.

PubMed

Gilani, Nima; Malcolm, Paul; Johnson, Glyn

2017-04-01

Diffusion MRI is used frequently to assess prostate cancer. The prostate consists of cellular tissue surrounding fluid filled ducts. Here, the diffusion properties of the ductal fluid alone were studied. Monte Carlo simulations were used to investigate ductal residence times to determine whether ducts can be regarded as forming a separate compartment and whether ductal radius could determine the Apparent Diffusion Coefficient (ADC) of the ductal fluid. Random walks were simulated in cavities. Average residence times were estimated for permeable cavities. Signal reductions resulting from application of a Stejskal-Tanner pulse sequence were calculated in impermeable cavities. Simulations were repeated for cavities of different radii and different diffusion times. Residence times are at least comparable with diffusion times even in relatively high grade tumors. ADCs asymptotically approach theoretical limiting values. At large radii and short diffusion times, ADCs are similar to free diffusion. At small radii and long diffusion times, ADCs are reduced toward zero, and kurtosis approaches a value of -1.2. Restricted diffusion in cavities of similar sizes to prostate ducts may reduce ductal ADCs. This may contribute to reductions in total ADC seen in prostate cancer. Magn Reson Med 77:1671-1677, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Super-resolution reconstruction of diffusion parameters from diffusion-weighted images with different slice orientations.

PubMed

Van Steenkiste, Gwendolyn; Jeurissen, Ben; Veraart, Jelle; den Dekker, Arnold J; Parizel, Paul M; Poot, Dirk H J; Sijbers, Jan

2016-01-01

Diffusion MRI is hampered by long acquisition times, low spatial resolution, and a low signal-to-noise ratio. Recently, methods have been proposed to improve the trade-off between spatial resolution, signal-to-noise ratio, and acquisition time of diffusion-weighted images via super-resolution reconstruction (SRR) techniques. However, during the reconstruction, these SRR methods neglect the q-space relation between the different diffusion-weighted images. An SRR method that includes a diffusion model and directly reconstructs high resolution diffusion parameters from a set of low resolution diffusion-weighted images was proposed. Our method allows an arbitrary combination of diffusion gradient directions and slice orientations for the low resolution diffusion-weighted images, optimally samples the q- and k-space, and performs motion correction with b-matrix rotation. Experiments with synthetic data and in vivo human brain data show an increase of spatial resolution of the diffusion parameters, while preserving a high signal-to-noise ratio and low scan time. Moreover, the proposed SRR method outperforms the previous methods in terms of the root-mean-square error. The proposed SRR method substantially increases the spatial resolution of MRI that can be obtained in a clinically feasible scan time. © 2015 Wiley Periodicals, Inc.

Reduce Confusion about Diffusion.

ERIC Educational Resources Information Center

Hebrank, Mary R.

1997-01-01

Presents activities that allow students to explore the fundamental but poorly understood concept of diffusion by appealing to their kinesthetic senses first, then challenging their analytical skills as they try to deduce the mathematical principle involved. Presents a computer simulation of diffusion and discusses diffusion's limitations and…

Instrumentation in Diffuse Optical Imaging

PubMed Central

Zhang, Xiaofeng

2014-01-01

Diffuse optical imaging is highly versatile and has a very broad range of applications in biology and medicine. It covers diffuse optical tomography, fluorescence diffuse optical tomography, bioluminescence, and a number of other new imaging methods. These methods of diffuse optical imaging have diversified instrument configurations but share the same core physical principle – light propagation in highly diffusive media, i.e., the biological tissue. In this review, the author summarizes the latest development in instrumentation and methodology available to diffuse optical imaging in terms of system architecture, light source, photo-detection, spectral separation, signal modulation, and lastly imaging contrast. PMID:24860804

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

Hydrodynamically induced fluid transfer and non-convective double-diffusion in microgravity sliding solvent diffusion cells

NASA Technical Reports Server (NTRS)

Pollmann, Konrad W.; Stodieck, Louis S.; Luttges, Marvin W.

1994-01-01

Microgravity can provide a diffusion-dominated environment for double-diffusion and diffusion-reaction experiments otherwise disrupted by buoyant convection or sedimentation. In sliding solvent diffusion cells, a diffusion interface between two liquid columns is achieved by aligning two offset sliding wells. Fluid in contact with the sliding lid of the cavities is subjected to an applied shear stress. The momentum change by the start/stop action of the well creates an additional hydrodynamical force. In microgravity, these viscous and inertial forces are sufficiently large to deform the diffusion interface and induce hydrodynamic transfer between the wells. A series of KC-135 parabolic flight experiments were conducted to characterize these effects and establish baseline data for microgravity diffusion experiments. Flow visualizations show the diffusion interface to be deformed in a sinusoidal fashion following well alignment. After the wells were separated again in a second sliding movement, the total induced liquid transfer was determined and normalized by the well aspect ratio. The normalized transfer decreased linearly with Reynolds number from 3.3 to 4.0% (w/v) for Re = 0.4 (Stokes flow) to a minimum of 1.0% for Re = 23 to 30. Reynolds numbers that provide minimum induced transfers are characterized by an interface that is highly deformed and unsuitable for diffusion measurements. Flat diffusion interfaces acceptable for diffusion measurements are obtained with Reynolds numbers on the order of 7 to 10. Microgravity experiments aboard a sounding rocket flight verified counterdiffusion of different solutes to be diffusion dominated. Ground control experiments showed enhanced mixing by double-diffusive convection. Careful selection of experimental parameters improves initial conditions and minimizes induced transfer rates.

Gaseous diffusion system

DOEpatents

Garrett, George A.; Shacter, John

1978-01-01

1. A gaseous diffusion system comprising a plurality of diffusers connected in cascade to form a series of stages, each of said diffusers having a porous partition dividing it into a high pressure chamber and a low pressure chamber, and means for combining a portion of the enriched gas from a succeeding stage with a portion of the enriched gas from the low pressure chamber of each stage and feeding it into one extremity of the high pressure chamber thereof.

Estimating the Diffusion Coefficients of Sugars Using Diffusion Experiments in Agar-Gel and Computer Simulations.

PubMed

Miyamoto, Shuichi; Atsuyama, Kenji; Ekino, Keisuke; Shin, Takashi

2018-01-01

The isolation of useful microbes is one of the traditional approaches for the lead generation in drug discovery. As an effective technique for microbe isolation, we recently developed a multidimensional diffusion-based gradient culture system of microbes. In order to enhance the utility of the system, it is favorable to have diffusion coefficients of nutrients such as sugars in the culture medium beforehand. We have, therefore, built a simple and convenient experimental system that uses agar-gel to observe diffusion. Next, we performed computer simulations-based on random-walk concepts-of the experimental diffusion system and derived correlation formulas that relate observable diffusion data to diffusion coefficients. Finally, we applied these correlation formulas to our experimentally-determined diffusion data to estimate the diffusion coefficients of sugars. Our values for these coefficients agree reasonably well with values published in the literature. The effectiveness of our simple technique, which has elucidated the diffusion coefficients of some molecules which are rarely reported (e.g., galactose, trehalose, and glycerol) is demonstrated by the strong correspondence between the literature values and those obtained in our experiments.

Artifact correction in diffusion MRI of non-human primate brains on a clinical 3T scanner.

PubMed

Zhang, Xiaodong; Kirsch, John E; Zhong, Xiaodong

2016-02-01

Smearing artifacts were observed and investigated in diffusion tensor imaging (DTI) studies of macaque monkeys on a clinical whole-body 3T scanner. Four adult macaques were utilized to evaluate DTI artifacts. DTI images were acquired with a single-shot echo-planar imaging (EPI) sequence using a parallel imaging technique. The smearing artifacts observed on the diffusion-weighted images and fractional anisotropy maps were caused by the incomplete fat suppression due to the irregular macaque frontal skull geometry and anatomy. The artifact can be reduced substantially using a novel three-dimensional (3D) shimming procedure. The smearing artifacts observed on diffusion weighted images and fractional anisotropy (FA) maps of macaque brains can be reduced substantially using a robust 3D shimming approach. The DTI protocol combined with the shimming procedure could be a robust approach to examine brain connectivity and white matter integrity of non-human primates using a conventional clinical setting. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A framework to analyze cerebral mean diffusivity using surface guided diffusion mapping in diffusion tensor imaging

PubMed Central

Kwon, Oh-Hun; Park, Hyunjin; Seo, Sang-Won; Na, Duk L.; Lee, Jong-Min

2015-01-01

The mean diffusivity (MD) value has been used to describe microstructural properties in Diffusion Tensor Imaging (DTI) in cortical gray matter (GM). Recently, researchers have applied a cortical surface generated from the T1-weighted volume. When the DTI data are analyzed using the cortical surface, it is important to assign an accurate MD value from the volume space to the vertex of the cortical surface, considering the anatomical correspondence between the DTI and the T1-weighted image. Previous studies usually sampled the MD value using the nearest-neighbor (NN) method or Linear method, even though there are geometric distortions in diffusion-weighted volumes. Here we introduce a Surface Guided Diffusion Mapping (SGDM) method to compensate for such geometric distortions. We compared our SGDM method with results using NN and Linear methods by investigating differences in the sampled MD value. We also projected the tissue classification results of non-diffusion-weighted volumes to the cortical midsurface. The CSF probability values provided by the SGDM method were lower than those produced by the NN and Linear methods. The MD values provided by the NN and Linear methods were significantly greater than those of the SGDM method in regions suffering from geometric distortion. These results indicate that the NN and Linear methods assigned the MD value in the CSF region to the cortical midsurface (GM region). Our results suggest that the SGDM method is an effective way to correct such mapping errors. PMID:26236180

Isotope fractionation by multicomponent diffusion (Invited)

NASA Astrophysics Data System (ADS)

Watkins, J. M.; Liang, Y.; Richter, F. M.; Ryerson, F. J.; DePaolo, D. J.

2013-12-01

Isotope fractionation by multicomponent diffusion The isotopic composition of mineral phases can be used to probe the temperatures and rates of mineral formation as well as the degree of post-mineralization alteration. The ability to interpret stable isotope variations is limited by our knowledge of three key parameters and their relative importance in determining the composition of a mineral grain and its surroundings: (1) thermodynamic (equilibrium) partitioning, (2) mass-dependent diffusivities, and (3) mass-dependent reaction rate coefficients. Understanding the mechanisms of diffusion and reaction in geological liquids, and how these mass transport processes discriminate between isotopes, represents an important problem that is receiving considerable attention in the geosciences. Our focus in this presentation will be isotope fractionation by chemical diffusion. Previous studies have documented that diffusive isotope effects vary depending on the cation as well as the liquid composition, but the ability to predict diffusive isotope effects from theory is limited; for example, it is unclear whether the magnitude of diffusive isotopic fractionations might also vary with the direction of diffusion in composition space. To test this hypothesis and to further guide the theoretical treatment of isotope diffusion, two chemical diffusion experiments and one self diffusion experiment were conducted at 1250°C and 0.7 GPa. In one experiment (A-B), CaO and Na2O counter-diffuse rapidly in the presence of a small SiO2 gradient. In the other experiment (D-E), CaO and SiO2 counter-diffuse more slowly in a small Na2O gradient. In both chemical diffusion experiments, Ca isotopes become fractionated by chemical diffusion but by different amounts, documenting for the first time that the magnitude of isotope fractionation by diffusion depends on the direction of diffusion in composition space. The magnitude of Ca isotope fractionation that develops is positively correlated with

NMR-based diffusion pore imaging.

PubMed

Laun, Frederik Bernd; Kuder, Tristan Anselm; Wetscherek, Andreas; Stieltjes, Bram; Semmler, Wolfhard

2012-08-01

Nuclear magnetic resonance (NMR) diffusion experiments offer a unique opportunity to study boundaries restricting the diffusion process. In a recent Letter [Phys. Rev. Lett. 107, 048102 (2011)], we introduced the idea and concept that such diffusion experiments can be interpreted as NMR imaging experiments. Consequently, images of closed pores, in which the spins diffuse, can be acquired. In the work presented here, an in-depth description of the diffusion pore imaging technique is provided. Image artifacts due to gradient profiles of finite duration, field inhomogeneities, and surface relaxation are considered. Gradients of finite duration lead to image blurring and edge enhancement artifacts. Field inhomogeneities have benign effects on diffusion pore images, and surface relaxation can lead to a shrinkage and shift of the pore image. The relation between boundary structure and the imaginary part of the diffusion weighted signal is analyzed, and it is shown that information on pore coherence can be obtained without the need to measure the phase of the diffusion weighted signal. Moreover, it is shown that quite arbitrary gradient profiles can be used for diffusion pore imaging. The matrices required for numerical calculations are stated and provided as supplemental material.

Effects of Diffusion Time on Short-Range Hyperpolarized 3He Diffusivity Measurements in Emphysema

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gierada, David S.; Woods, Jason C.; Bierhals, Andrew J.

2009-09-28

Purpose: To characterize the effect of diffusion time on short-range hyperpolarized 3He MR diffusion measurements across a wide range of emphysema severity. Materials and Methods: 3He diffusion MR imaging was performed on 19 lungs or lobes resected from 18 subjects with varying degrees of emphysema using 3 diffusion times (1.6 msec, 5 msec, and 10 msec) at constant b value. Emphysema severity was quantified as the mean apparent diffusion coefficient (ADC) and as the percentage of pixels with ADC higher than multiple thresholds from 0.30-0.55 cm2/sec (ADC index). Quantitative histology (mean linear intercept) was obtained in 10 of the lungmore » specimens from 10 of the subjects. Results: The mean ADCs with diffusion times of 1.6, 5.0, and 10.0 msec were 0.46, 0.40, and 0.37 cm2/sec, respectively (P <0.0001, ANOVA). There was no relationship between the ADC magnitude and the effect of diffusion time on ADC values. Mean linear intercept correlated with ADC (r=0.91-0.94, P<0.001) and ADC index (r=0.78-0.92, P<0.01) at all diffusion times.« less

Functional localization of the human color center by decreased water displacement using diffusion-weighted fMRI.

PubMed

Williams, Rebecca J; Reutens, David C; Hocking, Julia

2015-11-01

Decreased water displacement following increased neural activity has been observed using diffusion-weighted functional MRI (DfMRI) at high b-values. The physiological mechanisms underlying the diffusion signal change may be unique from the standard blood oxygenation level-dependent (BOLD) contrast and closer to the source of neural activity. Whether DfMRI reflects neural activity more directly than BOLD outside the primary cerebral regions remains unclear. Colored and achromatic Mondrian visual stimuli were statistically contrasted to functionally localize the human color center Area V4 in neurologically intact adults. Spatial and temporal properties of DfMRI and BOLD activation were examined across regions of the visual cortex. At the individual level, DfMRI activation patterns showed greater spatial specificity to V4 than BOLD. The BOLD activation patterns were more prominent in the primary visual cortex than DfMRI, where activation was localized to the ventral temporal lobe. Temporally, the diffusion signal change in V4 and V1 both preceded the corresponding hemodynamic response, however the early diffusion signal change was more evident in V1. DfMRI may be of use in imaging applications implementing cognitive subtraction paradigms, and where highly precise individual functional localization is required.

Similarity solutions of reaction–diffusion equation with space- and time-dependent diffusion and reaction terms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ho, C.-L.; Lee, C.-C., E-mail: chieh.no27@gmail.com

2016-01-15

We consider solvability of the generalized reaction–diffusion equation with both space- and time-dependent diffusion and reaction terms by means of the similarity method. By introducing the similarity variable, the reaction–diffusion equation is reduced to an ordinary differential equation. Matching the resulting ordinary differential equation with known exactly solvable equations, one can obtain corresponding exactly solvable reaction–diffusion systems. Several representative examples of exactly solvable reaction–diffusion equations are presented.

Diffuse reflectance relations based on diffusion dipole theory for large absorption and reduced scattering

NASA Astrophysics Data System (ADS)

Bremmer, Rolf H.; van Gemert, Martin J. C.; Faber, Dirk J.; van Leeuwen, Ton G.; Aalders, Maurice C. G.

2013-08-01

Diffuse reflectance spectra are used to determine the optical properties of biological samples. In medicine and forensic science, the turbid objects under study often possess large absorption and/or scattering properties. However, data analysis is frequently based on the diffusion approximation to the radiative transfer equation, implying that it is limited to tissues where the reduced scattering coefficient dominates over the absorption coefficient. Nevertheless, up to absorption coefficients of 20 m at reduced scattering coefficients of 1 and 11.5 mm-1, we observed excellent agreement (r2=0.994) between reflectance measurements of phantoms and the diffuse reflectance equation proposed by Zonios et al. [Appl. Opt. 38, 6628-6637 (1999)], derived as an approximation to one of the diffusion dipole equations of Farrell et al. [Med. Phys. 19, 879-888 (1992)]. However, two parameters were fitted to all phantom experiments, including strongly absorbing samples, implying that the reflectance equation differs from diffusion theory. Yet, the exact diffusion dipole approximation at high reduced scattering and absorption also showed agreement with the phantom measurements. The mathematical structure of the diffuse reflectance relation used, derived by Zonios et al. [Appl. Opt. 38, 6628-6637 (1999)], explains this observation. In conclusion, diffuse reflectance relations derived as an approximation to the diffusion dipole theory of Farrell et al. can analyze reflectance ratios accurately, even for much larger absorption than reduced scattering coefficients. This allows calibration of fiber-probe set-ups so that the object's diffuse reflectance can be related to its absorption even when large. These findings will greatly expand the application of diffuse reflection spectroscopy. In medicine, it may allow the use of blue/green wavelengths and measurements on whole blood, and in forensic science, it may allow inclusion of objects such as

Stochastic mechanics of reciprocal diffusions

NASA Astrophysics Data System (ADS)

Levy, Bernard C.; Krener, Arthur J.

1996-02-01

The dynamics and kinematics of reciprocal diffusions were examined in a previous paper [J. Math. Phys. 34, 1846 (1993)], where it was shown that reciprocal diffusions admit a chain of conservation laws, which close after the first two laws for two disjoint subclasses of reciprocal diffusions, the Markov and quantum diffusions. For the case of quantum diffusions, the conservation laws are equivalent to Schrödinger's equation. The Markov diffusions were employed by Schrödinger [Sitzungsber. Preuss. Akad. Wiss. Phys. Math Kl. 144 (1931); Ann. Inst. H. Poincaré 2, 269 (1932)], Nelson [Dynamical Theories of Brownian Motion (Princeton University, Princeton, NJ, 1967); Quantum Fluctuations (Princeton University, Princeton, NJ, 1985)], and other researchers to develop stochastic formulations of quantum mechanics, called stochastic mechanics. We propose here an alternative version of stochastic mechanics based on quantum diffusions. A procedure is presented for constructing the quantum diffusion associated to a given wave function. It is shown that quantum diffusions satisfy the uncertainty principle, and have a locality property, whereby given two dynamically uncoupled but statistically correlated particles, the marginal statistics of each particle depend only on the local fields to which the particle is subjected. However, like Wigner's joint probability distribution for the position and momentum of a particle, the finite joint probability densities of quantum diffusions may take negative values.

Altered Development of White Matter in Youth at High Familial Risk for Bipolar Disorder: A Diffusion Tensor Imaging Study

ERIC Educational Resources Information Center

Versace, Amelia; Ladouceur, Cecile D.; Romero, Soledad; Birmaher, Boris; Axelson, David A.; Kupfer, David J.; Phillips, Mary L.

2010-01-01

Objective: To study white matter (WM) development in youth at high familial risk for bipolar disorder (BD). WM alterations are reported in youth and adults with BD. WM undergoes important maturational changes in adolescence. Age-related changes in WM microstructure using diffusion tensor imaging with tract-based spatial statistics in healthy…

High-grade glioma diffusive modeling using statistical tissue information and diffusion tensors extracted from atlases.

PubMed

Roniotis, Alexandros; Manikis, Georgios C; Sakkalis, Vangelis; Zervakis, Michalis E; Karatzanis, Ioannis; Marias, Kostas

2012-03-01

Glioma, especially glioblastoma, is a leading cause of brain cancer fatality involving highly invasive and neoplastic growth. Diffusive models of glioma growth use variations of the diffusion-reaction equation in order to simulate the invasive patterns of glioma cells by approximating the spatiotemporal change of glioma cell concentration. The most advanced diffusive models take into consideration the heterogeneous velocity of glioma in gray and white matter, by using two different discrete diffusion coefficients in these areas. Moreover, by using diffusion tensor imaging (DTI), they simulate the anisotropic migration of glioma cells, which is facilitated along white fibers, assuming diffusion tensors with different diffusion coefficients along each candidate direction of growth. Our study extends this concept by fully exploiting the proportions of white and gray matter extracted by normal brain atlases, rather than discretizing diffusion coefficients. Moreover, the proportions of white and gray matter, as well as the diffusion tensors, are extracted by the respective atlases; thus, no DTI processing is needed. Finally, we applied this novel glioma growth model on real data and the results indicate that prognostication rates can be improved. © 2012 IEEE

A Student Diffusion Activity

ERIC Educational Resources Information Center

Kutzner, Mickey; Pearson, Bryan

2017-01-01

Diffusion is a truly interdisciplinary topic bridging all areas of STEM education. When biomolecules are not being moved through the body by fluid flow through the circulatory system or by molecular motors, diffusion is the primary mode of transport over short distances. The direction of the diffusive flow of particles is from high concentration…

NASA/DoD Aerospace Knowledge Diffusion Research Project, Paper Sixteen: Aerospace Knowledge Diffusion Research

DTIC Science & Technology

1991-01-01

Understanding how STI is commun- aerospace knowledge- efficient and effective transfer and cated in the process of technolgical diffusion of knowledge within...However, as important international levels, diffusion of knowledge in the aeros- as the transfer and utilisation of STI is to which will help to pace...diffused is neces- diffusion of knowledge . Phase 3 ex- formation specialist). Phase 2 examined sary to successfully manage technolog- plores the information

Continuous diffusion signal, EAP and ODF estimation via Compressive Sensing in diffusion MRI.

PubMed

Merlet, Sylvain L; Deriche, Rachid

2013-07-01

In this paper, we exploit the ability of Compressed Sensing (CS) to recover the whole 3D Diffusion MRI (dMRI) signal from a limited number of samples while efficiently recovering important diffusion features such as the Ensemble Average Propagator (EAP) and the Orientation Distribution Function (ODF). Some attempts to use CS in estimating diffusion signals have been done recently. However, this was mainly an experimental insight of CS capabilities in dMRI and the CS theory has not been fully exploited. In this work, we also propose to study the impact of the sparsity, the incoherence and the RIP property on the reconstruction of diffusion signals. We show that an efficient use of the CS theory enables to drastically reduce the number of measurements commonly used in dMRI acquisitions. Only 20-30 measurements, optimally spread on several b-value shells, are shown to be necessary, which is less than previous attempts to recover the diffusion signal using CS. This opens an attractive perspective to measure the diffusion signals in white matter within a reduced acquisition time and shows that CS holds great promise and opens new and exciting perspectives in diffusion MRI (dMRI). Copyright © 2013 Elsevier B.V. All rights reserved.

Diffusion properties of NAA in human corpus callosum as studied with diffusion tensor spectroscopy.

PubMed

Upadhyay, Jaymin; Hallock, Kevin; Erb, Kelley; Kim, Dae-Shik; Ronen, Itamar

2007-11-01

In diffusion tensor imaging (DTI) the anisotropic movement of water is exploited to characterize microstructure. One confounding issue of DTI is the presence of intra- and extracellular components contributing to the measured diffusivity. This causes an ambiguity in determining the underlying cause of diffusion properties, particularly the fractional anisotropy (FA). In this study an intracellular constituent, N-acetyl aspartate (NAA), was used to probe intracellular diffusion, while water molecules were used to probe the combined intra- and extracellular diffusion. NAA and water diffusion measurements were made in anterior and medial corpus callosum (CC) regions, which are referred to as R1 and R2, respectively. FA(NAA) was found to be greater than FA(Water) in both CC regions, thus indicating a higher degree of anisotropy within the intracellular space in comparison to the combined intra- and extracellular spaces. A decreasing trend in the FA of NAA and water was observed between R1 and R2, while the radial diffusivity (RD) for both molecules increased. The increase in RD(NAA) is particularly significant, thus explaining the more significant decrease in FA(NAA) between the two regions. It is suggested that diffusion tensor spectroscopy of NAA can potentially be used to further characterize microscopic anatomic organization in white matter. Copyright 2007 Wiley-Liss, Inc.

Oxaliplatin in Treating Young Patients With Recurrent Solid Tumors That Have Not Responded to Previous Treatment

ClinicalTrials.gov

2013-06-04

Childhood Central Nervous System Germ Cell Tumor; Childhood Extragonadal Germ Cell Tumor; Childhood Hepatoblastoma; Childhood Hepatocellular Carcinoma; Childhood High-grade Cerebral Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Malignant Ovarian Germ Cell Tumor; Childhood Malignant Testicular Germ Cell Tumor; Childhood Teratoma; Recurrent Adrenocortical Carcinoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Liver Cancer; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Colon Cancer; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Nasopharyngeal Cancer; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Recurrent Rectal Cancer; Recurrent Renal Cell Cancer

Ispinesib in Treating Young Patients With Relapsed or Refractory Solid Tumors or Lymphoma

ClinicalTrials.gov

2013-01-15

Childhood Burkitt Lymphoma; Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Spinal Cord Neoplasm; Childhood Supratentorial Ependymoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Brain Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Unspecified Childhood Solid Tumor, Protocol Specific

FR901228 in Treating Children With Refractory or Recurrent Solid Tumors or Leukemia

ClinicalTrials.gov

2013-01-15

Blastic Phase Chronic Myelogenous Leukemia; Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Chronic Myelogenous Leukemia; Childhood Craniopharyngioma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Spinal Cord Neoplasm; Childhood Supratentorial Ependymoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Refractory Chronic Lymphocytic Leukemia; Relapsing Chronic Myelogenous Leukemia; Unspecified Childhood Solid Tumor, Protocol Specific

Effect of diffusive and nondiffusive surfaces combinations on sound diffusion

NASA Astrophysics Data System (ADS)

Shafieian, Masoume; Kashani, Farokh Hodjat

2010-05-01

One of room acoustic goals, especially in small to medium rooms, is sound diffusion in low frequencies, which have been the subject of lots of researches. Sound diffusion is a very important consideration in acoustics because it minimizes the coherent reflections that cause problems. It also tends to make an enclosed space sound larger than it is. Diffusion is an excellent alternative or complement to sound absorption in acoustic treatment because it doesn’t really remove much energy, which means it can be used to effectively reduce reflections while still leaving an ambient or live sounding space. Distribution of diffusive and nondiffusive surfaces on room walls affect sound diffusion in room, but the amount, combination, and location of these surfaces are still the matter of question. This paper investigates effects of these issues on room acoustic frequency response in different parts of the room with different source-receiver locations. Room acoustic model based on wave method is used (implemented) which is very accurate and convenient for low frequencies in such rooms. Different distributions of acoustic surfaces on room walls have been introduced to the model and room frequency response results are calculated. For the purpose of comparison, some measurements results are presented. Finally for more smooth frequency response in small and medium rooms, some suggestions are made.

White matter changes after stroke in type 2 diabetic rats measured by diffusion magnetic resonance imaging.

PubMed

Ding, Guangliang; Chen, Jieli; Chopp, Michael; Li, Lian; Yan, Tao; Davoodi-Bojd, Esmaeil; Li, Qingjiang; Davarani, Siamak Pn; Jiang, Quan

2017-01-01

Diffusion-related magnetic resonance imaging parametric maps may be employed to characterize white matter of brain. We hypothesize that entropy of diffusion anisotropy may be most effective for detecting therapeutic effects of bone marrow stromal cell treatment of ischemia in type 2 diabetes mellitus rats. Type 2 diabetes mellitus was induced in adult male Wistar rats. These rats were then subjected to 2 h of middle cerebral artery occlusion, and received bone marrow stromal cell (5 × 10 6 , n = 8) or an equal volume of saline (n = 8) via tail vein injection at three days after middle cerebral artery occlusion. Magnetic resonance imaging was performed on day one and then weekly for five weeks post middle cerebral artery occlusion. The diffusion metrics complementarily permitted characterization of axons and axonal myelination. All six magnetic resonance imaging diffusion metrics, confirmed by histological measures, demonstrated that bone marrow stromal cell treatment significantly (p < 0.05) improved magnetic resonance imaging diffusion indices of white matter in type 2 diabetes mellitus rats after middle cerebral artery occlusion compared with the saline-treated rats. Superior to the fractional anisotropy metric that provided measures related to organization of neuronal fiber bundles, the entropy metric can also identify microstructures and low-density axonal fibers of cerebral tissue after stroke in type 2 diabetes mellitus rats. © The Author(s) 2015.

White matter changes after stroke in type 2 diabetic rats measured by diffusion magnetic resonance imaging

PubMed Central

Ding, Guangliang; Chen, Jieli; Chopp, Michael; Li, Lian; Yan, Tao; Davoodi-Bojd, Esmaeil; Li, Qingjiang; Davarani, Siamak PN

2015-01-01

Diffusion-related magnetic resonance imaging parametric maps may be employed to characterize white matter of brain. We hypothesize that entropy of diffusion anisotropy may be most effective for detecting therapeutic effects of bone marrow stromal cell treatment of ischemia in type 2 diabetes mellitus rats. Type 2 diabetes mellitus was induced in adult male Wistar rats. These rats were then subjected to 2 h of middle cerebral artery occlusion, and received bone marrow stromal cell (5 × 106, n = 8) or an equal volume of saline (n = 8) via tail vein injection at three days after middle cerebral artery occlusion. Magnetic resonance imaging was performed on day one and then weekly for five weeks post middle cerebral artery occlusion. The diffusion metrics complementarily permitted characterization of axons and axonal myelination. All six magnetic resonance imaging diffusion metrics, confirmed by histological measures, demonstrated that bone marrow stromal cell treatment significantly (p < 0.05) improved magnetic resonance imaging diffusion indices of white matter in type 2 diabetes mellitus rats after middle cerebral artery occlusion compared with the saline-treated rats. Superior to the fractional anisotropy metric that provided measures related to organization of neuronal fiber bundles, the entropy metric can also identify microstructures and low-density axonal fibers of cerebral tissue after stroke in type 2 diabetes mellitus rats. PMID:26685128

Characterization of diffuse orbital mass using Apparent diffusion coefficient in 3-tesla MRI.

PubMed

ElKhamary, Sahar M; Galindo-Ferreiro, Alicia; AlGhafri, Laila; Khandekar, Rajiv; Schellini, Silvana Artioli

2018-01-01

To evaluate if the apparent diffusion coefficient (ADC) value in diffusion-weighted magnetic resonance imaging (DW-MRI) improves the diagnostic accuracy of diffuse orbital masses. ADC DW-MRI was used to evaluate cases of diffuse orbital masses at our institution from 2000 to 2015. Lesions were grouped according to histopathologic diagnosis as, benign, pre-malignant and malignant. Lymphoproliferative lesions were further subgrouped as lymphoma or other lymphoproliferative lesions. The validity of the ADC value for the diffuse orbital mass was compared between groups. The area under curve (AUC) was also calculated. Thirty-nine cases of diffuse orbital masses were evaluated. The median ADC was 0.58 (25% quartile 0.48; minimum: 0.45; maximum: 1.72 × 10 (-3) ) for the malignant tumors and 1.19 (25% quartile 0.7; minimum: 0.5; maximum: 1.95 × 10 (-3)  mm (2)  s (-1) ) for benign lesions. This difference in ADC between lesions was statistically significant (Mann Whitney U test P < 0.001). The median ADC was 0.51 (25% quartile 0.48) for lymphomas and 0.9 (25% quartile 0.7) for other lymphoproliferative lesions. This difference in ADC was statistically significant (Mann Whitney U test P = 0.02). An ADC value of 0.8 × 10 (-3)  mm (2)  s (-1) was noted as the ideal threshold value for differentiating malignant from benign diffuse orbital masses. The validity of ADC in predicting a malignant or benign diffuse orbital mass had a sensitivity of 87%, specificity of 67% and accuracy of 88%. ADC is a promising imaging metric to characterize malignant and benign diffuse orbital masses and to distinguish lymphomas from other non-lymphoproliferative lesions.

Quantum State Diffusion

NASA Astrophysics Data System (ADS)

Percival, Ian

2005-10-01

1. Introduction; 2. Brownian motion and Itô calculus; 3. Open quantum systems; 4. Quantum state diffusion; 5. Localisation; 6. Numerical methods and examples; 7. Quantum foundations; 8. Primary state diffusion; 9. Classical dynamics of quantum localisation; 10. Semiclassical theory and linear dynamics.

Cerebral White Matter Integrity and Cognitive Aging: Contributions from Diffusion Tensor Imaging

PubMed Central

Madden, David J.; Bennett, Ilana J.; Song, Allen W.

2009-01-01

The integrity of cerebral white matter is critical for efficient cognitive functioning, but little is known regarding the role of white matter integrity in age-related differences in cognition. Diffusion tensor imaging (DTI) measures the directional displacement of molecular water and as a result can characterize the properties of white matter that combine to restrict diffusivity in a spatially coherent manner. This review considers DTI studies of aging and their implications for understanding adult age differences in cognitive performance. Decline in white matter integrity contributes to a disconnection among distributed neural systems, with a consistent effect on perceptual speed and executive functioning. The relation between white matter integrity and cognition varies across brain regions, with some evidence suggesting that age-related effects exhibit an anterior-posterior gradient. With continued improvements in spatial resolution and integration with functional brain imaging, DTI holds considerable promise, both for theories of cognitive aging and for translational application. PMID:19705281

Effects of inlet flow field conditions on the performance of centrifugal compressor diffusers: Part 2 -- Straight-channel diffuser

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deniz, S.; Greitzer, E.M.; Cumpsty, N.A.

2000-01-01

This is Part 2 of an examination of the influence of inlet flow conditions on the performance and operating range of centrifugal compressor vaned diffusers. The paper describes tests of a straight-channel type diffuser, sometimes called a wedge-vane diffuser, and compares the results with those from the discrete-passage diffusers described in Part 1. Effects of diffuser inlet Mach number, flow angle, blockage, and axial flow nonuniformity on diffuser pressure recovery and operating range are addressed. The straight-channel diffuser investigated has 30 vanes and was designed for the same aerodynamic duty as the discrete-passage diffuser described in Part 1. The rangesmore » of the overall pressure recovery coefficients were 0.50--0.78 for the straight-channel diffuser and 0.50--0.70 for the discrete-passage diffuser, except when the diffuser was choked. In other words, the maximum pressure recovery of the straight-channel diffuser was found to be roughly 10% higher than that of the discrete-passage diffuser investigated. The two types of diffuser showed similar behavior regarding the dependence of pressure recovery on diffuser inlet flow angle and the insensitivity of the performance to inlet flow field axial distortion and Mach number. The operating range of the straight-channel diffuser, as for the discrete-passage diffusers, was limited by the onset of rotating stall at a fixed momentum-averaged flow angle into the diffuser, which was for the straight-channel diffuser, {alpha}{sub crit} = 70 {+-} 0.5 deg. The background, nomenclature, and description of the facility and method are all given in Part 1.« less

Stimulated echo diffusion tensor imaging (STEAM-DTI) with varying diffusion times as a probe of breast tissue.

PubMed

Teruel, Jose R; Cho, Gene Y; Moccaldi Rt, Melanie; Goa, Pål E; Bathen, Tone F; Feiweier, Thorsten; Kim, Sungheon G; Moy, Linda; Sigmund, Eric E

2017-01-01

To explore the application of diffusion tensor imaging (DTI) for breast tissue and breast pathologies using a stimulated-echo acquisition mode (STEAM) with variable diffusion times. In this Health Insurance Portability and Accountability Act-compliant study, approved by the local institutional review board, eight patients and six healthy volunteers underwent an MRI examination at 3 Tesla including STEAM-DTI with several diffusion times ranging from 68.5 to 902.5 ms. A DTI model was fitted to the data for each diffusion time, and parametric maps of mean diffusivity, fractional anisotropy, axial diffusivity, and radial diffusivity were computed for healthy fibroglandular tissue (FGT) and lesions. The median value of radial diffusivity for FGT was fitted to a linear decay to obtain an estimation of the surface-to-volume ratio, from which the radial diameter was calculated. For healthy FGT, radial diffusivity presented a linear decay with the square root of the diffusion time resulting in a range of estimated radial diameters from 202 to 496 µm, while axial diffusivity presented a nearly time-independent diffusion. Residual fat signal was reduced at longer diffusion times due to the shorter T1 of fat. Residual fat signal to the overall signal in the healthy volunteers' FGT was found to range from 2.39% to 2.55% (shortest mixing time), and from 0.40% to 0.51% (longest mixing time) for the b500 images. The use of variable diffusion times may provide an in vivo noninvasive tool to probe diffusion lengths in breast tissue and breast pathology, and might aid by improving fat suppression at longer diffusion times. 2 J. Magn. Reson. Imaging 2017;45:84-93. © 2016 International Society for Magnetic Resonance in Medicine.