Sample records for high grade astrocytoma

  1. Differential proteomics analysis of low- and high-grade of astrocytoma using iTRAQ quantification (United States)

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


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

  2. Gene Expression Profiling of Chemokines and Their Receptors in Low and High Grade Astrocytoma (United States)

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


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

  3. Gene Expression Profiling of Chemokines and Their Receptors in Low and High Grade Astrocytoma (United States)

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


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

  4. Relationship Between Cytogenetic Complexity and Peritumoral Edema in High-Grade Astrocytoma. (United States)

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


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

  5. Pediatric high-grade astrocytomas: a distinct neuro-oncological paradigm. (United States)

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


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

  6. Transcriptional analysis of aggressiveness and heterogeneity across grades of astrocytomas. (United States)

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


    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

  7. Potential Utility of Visually AcceSAble Rembrandt Images Assessment in Brain Astrocytoma Grading. (United States)

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


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

  8. Current treatment of low grade astrocytoma

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    Pedersen, Christina Louise; Romner, Bertil


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

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

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


    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.

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

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


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

  11. EGR-1 is regulated by N-methyl-D-aspartate-receptor stimulation and associated with patient survival in human high grade astrocytomas. (United States)

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


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

  12. Serial changes in lymphocyte subsets in patients with newly diagnosed high grade astrocytomas treated with standard radiation and temozolomide. (United States)

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


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

  13. Successful Management of Intraoperative Acute Bilateral Pulmonary Embolism in a High Grade Astrocytoma Patient. (United States)

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


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

  14. Tissue thioredoxin reductase-1 expression in astrocytomas of different grades. (United States)

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


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

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

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    SHEN Jun-lin


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

  16. The molecular biology of WHO grade I astrocytomas. (United States)

    Marko, Nicholas F; Weil, Robert J


    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.

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

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


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

  18. Radio-chemotherapy improves survival in IDH-mutant, 1p/19q non-codeleted secondary high-grade astrocytoma patients. (United States)

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


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

  19. Long-term daily temozolomide with dose-dependent efficacy in MGMT promotor methylation negative recurrent high-grade astrocytoma. (United States)

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


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

  20. Transcriptome analysis reveals distinct gene expression profiles in astrocytoma grades II-IV. (United States)

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


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

  1. Tumor Grade versus Expression of Invasion-Related Molecules in Astrocytoma. (United States)

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


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

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

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

    Directory of Open Access Journals (Sweden)

    Chelsea eEkstrand


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

  4. Hydrogel Environment Supports Cell Culture Expansion of a Grade IV Astrocytoma. (United States)

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


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

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

    NARCIS (Netherlands)

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


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

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

    DEFF Research Database (Denmark)

    Christensen, Karina; Schrøder, Henrik; Kristensen, Bjarne


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

  7. WHO grade-specific comparative genomic hybridization pattern of astrocytoma - a meta-analysis. (United States)

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


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

  8. Tipifarnib in Treating Young Patients With Recurrent or Progressive High-Grade Glioma, Medulloblastoma, Primitive Neuroectodermal Tumor, or Brain Stem Glioma (United States)


    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

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

  10. Rapid malignant transformation of low-grade astrocytoma in a pregnant woman. (United States)

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


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

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

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


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

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

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


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

  13. A case of an epithelioid glioblastoma with the BRAF V600E mutation colocalized with BRAF intact low-grade diffuse astrocytoma. (United States)

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


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

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

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


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

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

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


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

  16. Low grade astrocytoma causing dural and calvarial destruction. (United States)

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


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

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

    Directory of Open Access Journals (Sweden)

    Alaa Alkhotani


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

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

    NARCIS (Netherlands)

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


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

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

    NARCIS (Netherlands)

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


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

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

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


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

  1. Perinatal (fetal and neonatal) astrocytoma: a review. (United States)

    Isaacs, Hart


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

  2. Concurrent TERT promoter and BRAF V600E mutation in epithelioid glioblastoma and concomitant low-grade astrocytoma. (United States)

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


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

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

    Directory of Open Access Journals (Sweden)

    André de Macedo Bianco


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

  4. Diffuse Astrocytoma, IDH-Wildtype: A Dissolving Diagnosis. (United States)

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


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

  5. Impact of Resection on Survival of Isocitrate Dehydrogenase 1-Mutated World Health Organization Grade II Astrocytoma After Malignant Progression. (United States)

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


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

  6. 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 (United States)


    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

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

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    Irene Rodríguez-Hernández

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Kaellen, K


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

  9. Nitroproteins in Human Astrocytomas Discovered by Gel Electrophoresis and Tandem Mass Spectrometry (United States)

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


    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

  10. Overexpression of Eg5 correlates with high grade astrocytic neoplasm. (United States)

    Liu, Liqiong; Liu, Xichun; Mare, Marcus; Dumont, Aaron S; Zhang, Haitao; Yan, Dong; Xiong, Zhenggang


    To investigate the relationship between Eg5 and histopathological grade of astrocytoma, Eg5 expression was evaluated by immunohistochemical examination on 88 specimens including 25 cases of glioblastoma (WHO grade IV), 22 cases of anaplastic astrocytoma (WHO grade III), 20 cases of diffuse astrocytoma (WHO grade II), and 21 cases of pilocytic astrocytoma (WHO grade I). The histopathological characteristics and Eg5 expression level of each tumor were assessed and statistically analyzed. Astrocytic tumors exhibited significant correlation of expression of Eg5 with higher WHO histopathological grades (p neoplasm, and it may represent an independent diagnostic and prognostic factor in grading astrocytic tumors and predicting prognosis of astrocytic tumor patients.

  11. Overexpression of Fli-1 in astrocytoma is associated with poor prognosis. (United States)

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


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

  12. Juvenile Pilocytic Astrocytoma in Association with Arteriovenous Malformation


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


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

  13. Evaluation of miR-362 Expression in Astrocytoma of Human Brain Tumors (United States)

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


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

  14. Expression of neuronal markers, NFP and GFAP, in malignant astrocytoma. (United States)

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


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

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

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    Aram S. Modrek


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

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

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    Paola Rognoni


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

  17. GFAPδ/GFAPα ratio directs astrocytoma gene expression towards a more malignant profile (United States)

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


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

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

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


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

  19. Expression patterns of Wnt signaling component, secreted frizzled‑related protein 3 in astrocytoma and glioblastoma. (United States)

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


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

  20. Expression patterns of Wnt signaling component, secreted frizzled-related protein 3 in astrocytoma and glioblastoma (United States)



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

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

    NARCIS (Netherlands)

    F.K. Aarsen (Femke)


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

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

    Carlberg, Michael; Hardell, Lennart


    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.

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

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


    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.

  4. A retrospective observational study on the treatment outcomes of 26 patients with spinal cord astrocytoma including two cases of malignant transformation. (United States)

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


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

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

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    Anke Waha


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

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

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    Michael Carlberg


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

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

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


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

  8. Anaplastic astrocytoma. (United States)

    Grimm, Sean A; Chamberlain, Marc C


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

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

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    Soumya Alige Mahabala Rao

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

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

    NARCIS (Netherlands)

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


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

  11. Juvenile pilocytic astrocytoma in association with arteriovenous malformation. (United States)

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


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

  12. Pilocytic astrocytoma: A rare presentation as intraventricular tumor (United States)

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


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

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

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


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

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

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    Varini Karine


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

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

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    Qinchuan Liang

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

  16. Pilomyxoid astrocytoma of the brainstem

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    Marco Antonio Zanini


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

  17. Prognostic parameters in benign astrocytomas

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    Westergaard, L; Gjerris, F; Klinken, L


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

  18. MRI of high-grade astrocytic tumors: early appearance and evolution

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    Okamoto, K.; Takahashi, N.; Ishikawa, K.; Furusawa, T.; Sakai, K. [Department of Radiology, Niigata University Faculty of Medicine (Japan); Ito, J.; Tokiguchi, S. [Department of Radiology, Niigata University Faculty of Dentistry (Japan)


    The clinical management and prognosis of patients with diffusely infiltrating astrocytomas are dependent on neuropathological grading of the tumors. The characteristics of MR images of high-grade astrocytic tumors are well known, but the early MRI appearance and the MRI evolution of high-grade astrocytic tumors have rarely been examined. We retrospectively reviewed MR images obtained from 4 months to 3 years and 3 months before admission, as well as MR images on admission, for five patients with pathologically proven high-grade astrocytic tumors (two glioblastomas and three anaplastic astrocytomas). In two patients, neoplastic lesions were not detectable on initial MRI, even retrospectively. In the remaining three patients, however, hyperintense areas with little or no mass effect were demonstrated on T2-weighted imaging. These lesions were misinterpreted as non-neoplastic processes, such as ischemic lesion or infarction, or demyelinating processes. All tumors showed gadolinium enhancement on admission, that emerged from the previously existing hyperintense areas on T2-weighted images without gadolinium enhancement, except for one de novo glioblastoma. Development of a small central cyst without gadolinium enhancement was demonstrated in one case before the emergence of an enhancing area. (orig.)

  19. Rab23 is overexpressed in human astrocytoma and promotes cell migration and invasion through regulation of Rac1. (United States)

    Wang, Minghao; Dong, Qianze; Wang, Yunjie


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

  20. Fluorescence-guided surgery in high grade gliomas using an exoscope system. (United States)

    Belloch, José Piquer; Rovira, Vicente; Llácer, Jose L; Riesgo, Pedro A; Cremades, Antonio


    Fluorescence-guided microsurgical resections of high-grade gliomas using 5-aminolevulinic acid (5-ALA) is superior to conventional microsurgery. An optical device, usually a modified microscope, is needed for these procedures. However, an exoscope may be implemented for fluorescence techniques. We present the use of an exoscope to perform tumor resection guided by 5-ALA fluorescence in 21 consecutive patients with high-grade glioma and two neuronavigation-guided biopsies. Twenty-three patients underwent operations. Tumor volume and localization were quantified with pre- and postoperative volumetric MRI in non-biopsy cases. In non-biopsy cases, the age range was 20 to 79 years, with a median of 56 (interquartile range = 45-66). Histological analysis indicated that 14 had glioblastoma multiforme, 2 grade-III oligodendrogliomas and 1 anaplastic astrocytoma, 3 metastases and 1 low-grade astrocytoma. Total resection was achieved in 15 cases; subtotal resection was performed in 5 patients. The result was partial resection in one case. There was no perioperative mortality. The median fluorescence intensity, on a scale of 1-5, was 4.5 in the GBM group (IQR = 4-5), 3 (IQR = 2.5-3.5) in anaplastic glioma, and 2.5 (IQR = 2.25-2.75) for oligodendrogliomas. Of the three metastases, one showed fluorescence level 4. As for the two biopsy cases, one was anaplastic astrocytoma and one glioblastoma multiforme. The samples obtained were fluorescent in both cases. An exoscope can be also used for fluorescence-guided surgery with 5-aminolevulinic acid (5-ALA) and neuronavigation-guided biopsy. With an important advantage of low cost, this allows the surgeon to perform collaborative surgeries and adds agility to the procedure.

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

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    Maher Kurdi


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

  2. Prognostic parameters in benign astrocytomas

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    Westergaard, L; Gjerris, F; Klinken, L


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

  3. Pilomyxoid astrocytoma in the adult cerebellum. (United States)

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


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

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


    Ren T; Lin SD; Wang ZF; Shang AJ


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

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

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    Dely Cristina Martins


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

  6. Expression signatures of DNA repair genes correlate with survival prognosis of astrocytoma patients. (United States)

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


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

  7. Cerebral astrocytoma in a sheep (United States)

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


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

  8. Diffuse Infiltrating Oligodendroglioma and Astrocytoma. (United States)

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


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

  9. Adult anaplastic pilocytic astrocytoma - a diagnostic challenge? A case series and literature review. (United States)

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


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

  10. Stem cells and models of astrocytomas. (United States)

    Kamnasaran, Deepak


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

  11. Eya2 overexpression promotes the invasion of human astrocytoma through the regulation of ERK/MMP9 signaling (United States)

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


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

  12. Copy Number Profiling of Brazilian Astrocytomas

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    Lucas Tadeu Bidinotto


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

  13. Microscopic thrombi in anaplastic astrocytoma predict worse survival? (United States)

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


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

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

    DEFF Research Database (Denmark)

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

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

  15. [Clinical effects of microsurgery in spinal cord anaplastic astrocytoma]. (United States)

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


    and radiotherapy group were increased significantly(χ(2)=6.687, P=0.001; χ(2)=14.887, P=0.002). Conclusions: Spinal cord AA is a rare spinal high-grade astrocytoma with aggressive nature, the prognosis remains poor even after comprehensive treatments. Microsurgery followed by adjuvant chemoradiation is recommended for the treatment.

  16. Anorexia: an early sign of fourth ventricle astrocytoma in children. (United States)

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


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

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

    DEFF Research Database (Denmark)

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


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

  18. Paradoxical perfusion metrics of high-grade gliomas with an oligodendroglioma component: quantitative analysis of dynamic susceptibility contrast perfusion MR imaging

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    Sunwoo, Leonard; Park, Sun-Won [Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Seoul Metropolitan Government - Seoul National University Boramae Medical Center, Department of Radiology, Seoul (Korea, Republic of); Choi, Seung Hong [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Seoul National University, Center for Nanoparticle Research, Institute for Basic Science, and School of Chemical and Biological Engineering, Seoul (Korea, Republic of); Yoo, Roh-Eul; Kang, Koung Mi; Yun, Tae Jin; Kim, Ji-hoon; Sohn, Chul-Ho [Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Kim, Tae Min; Lee, Se-Hoon [Seoul National University Hospital, Department of Internal Medicine, Seoul (Korea, Republic of); Park, Chul-Kee [Seoul National University Hospital, Department of Neurosurgery, Seoul (Korea, Republic of); Won, Jae-Kyung; Park, Sung-Hye [Seoul National University Hospital, Department of Pathology, Seoul (Korea, Republic of); Kim, Il Han [Seoul National University Hospital, Department of Radiation Oncology, Seoul (Korea, Republic of)


    The aim of this study is to investigate perfusion characteristics of glioblastoma with an oligodendroglioma component (GBMO) compared with conventional glioblastoma (GBM) using dynamic susceptibility contrast (DSC) perfusion magnetic resonance (MR) imaging and microvessel density (MVD). The study was approved by the institutional review board. Newly diagnosed high-grade glioma patients were enrolled (n = 72; 20 GBMs, 14 GBMOs, 19 anaplastic astrocytomas (AAs), 13 anaplastic oligodendrogliomas (AOs), and six anaplastic oligoastrocytomas (AOAs)). All participants underwent preoperative MR imaging including DSC perfusion MR imaging. Normalized cerebral blood volume (nCBV) values were analyzed using a histogram approach. Histogram parameters were subsequently compared across each tumor subtype and grade. MVD was quantified by immunohistochemistry staining and correlated with perfusion parameters. Progression-free survival (PFS) was assessed according to the tumor subtype. GBMO displayed significantly reduced nCBV values compared with GBM, whereas grade III tumors with oligodendroglial components (AO and AOA) exhibited significantly increased nCBV values compared with AA (p < 0.001). MVD analyses revealed the same pattern as nCBV results. In addition, a positive correlation between MVD and nCBV values was noted (r = 0.633, p < 0.001). Patients with oligodendroglial tumors exhibited significantly increased PFS compared with patients with pure astrocytomas in each grade. In contrast to grade III tumors, the presence of oligodendroglial components in grade IV tumors resulted in paradoxically reduced perfusion metrics and MVD. In addition, patients with GBMO exhibited a better clinical outcome compared with patients with GBM. (orig.)

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

    Directory of Open Access Journals (Sweden)

    Maraziotis Theodore


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

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

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


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

  1. Vascular Endothelial Growth Factor as an Angiogenic Marker in Malignant Astrocytoma and Oligodendroglioma: An Indian Scenario (United States)

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


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

  2. and astrocyte and astrocytoma cells

    DEFF Research Database (Denmark)

    Tfelt-Hansen, J.


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

  3. Retinal astrocytoma in a dog. (United States)

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


    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.

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

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


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

  5. Heterogeneity of histopathological presentation of pilocytic astrocytoma - diagnostic pitfalls. A review. (United States)

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


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

  6. Effect of cognitive rehabilitation in a case of thalamic astrocytoma. (United States)

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


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

  7. Pilomyxoid Astrocytoma Occurring in the Third Ventricle

    Directory of Open Access Journals (Sweden)

    Sanghyeon Kim


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

  8. Magnetic resonance perfusion for differentiating low-grade from high-grade gliomas at first presentation. (United States)

    Abrigo, Jill M; Fountain, Daniel M; Provenzale, James M; Law, Eric K; Kwong, Joey Sw; Hart, Michael G; Tam, Wilson Wai San


    Gliomas are the most common primary brain tumour. They are graded using the WHO classification system, with Grade II-IV astrocytomas, oligodendrogliomas and oligoastrocytomas. Low-grade gliomas (LGGs) are WHO Grade II infiltrative brain tumours that typically appear solid and non-enhancing on magnetic resonance imaging (MRI) scans. People with LGG often have little or no neurologic deficit, so may opt for a watch-and-wait-approach over surgical resection, radiotherapy or both, as surgery can result in early neurologic disability. Occasionally, high-grade gliomas (HGGs, WHO Grade III and IV) may have the same MRI appearance as LGGs. Taking a watch-and-wait approach could be detrimental for the patient if the tumour progresses quickly. Advanced imaging techniques are increasingly used in clinical practice to predict the grade of the tumour and to aid clinical decision of when to intervene surgically. One such advanced imaging technique is magnetic resonance (MR) perfusion, which detects abnormal haemodynamic changes related to increased angiogenesis and vascular permeability, or "leakiness" that occur with aggressive tumour histology. These are reflected by changes in cerebral blood volume (CBV) expressed as rCBV (ratio of tumoural CBV to normal appearing white matter CBV) and permeability, measured by K trans . To determine the diagnostic test accuracy of MR perfusion for identifying patients with primary solid and non-enhancing LGGs (WHO Grade II) at first presentation in children and adults. In performing the quantitative analysis for this review, patients with LGGs were considered disease positive while patients with HGGs were considered disease negative.To determine what clinical features and methodological features affect the accuracy of MR perfusion. Our search strategy used two concepts: (1) glioma and the various histologies of interest, and (2) MR perfusion. We used structured search strategies appropriate for each database searched, which included: MEDLINE

  9. Clinical prognostic factors in adults with astrocytoma: Historic cohort. (United States)

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


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

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

    Directory of Open Access Journals (Sweden)

    Ifeoluwa Apanisile


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

  11. Bevacizumab Therapy for Pilomyxoid Astrocytoma. (United States)

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


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

  12. Anticancer activity of glucomoringin isothiocyanate in human malignant astrocytoma cells. (United States)

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


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

  13. Pilocytic Astrocytoma Enlargement Following Irradiation: Relapse or Pseudoprogression? (United States)

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


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

  14. Proton Beam Radiation Therapy in Treating Patients With Low Grade Gliomas (United States)


    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

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

    Directory of Open Access Journals (Sweden)

    André de Macedo Bianco


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

  16. Childhood Brain and Spinal Cord Tumors Treatment Overview (United States)

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

  17. General Information about Childhood Brain and Spinal Cord Tumors (United States)

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

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

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


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

  19. Alisertib and Fractionated Stereotactic Radiosurgery in Treating Patients With Recurrent High Grade Gliomas (United States)


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

  20. Tumor blood flow from arterial spin labeling perfusion MRI: a key parameter in distinguishing high-grade gliomas from primary cerebral lymphomas, and in predicting genetic biomarkers in high-grade gliomas. (United States)

    Yoo, Roh-Eul; Choi, Seung Hong; Cho, Hye Rim; Kim, Tae Min; Lee, Se-Hoon; Park, Chul-Kee; Park, Sung-Hye; Kim, Il Han; Yun, Tae Jin; Kim, Ji-Hoon; Sohn, Chul-Ho; Han, Moon Hee; Chang, Kee Hyun


    To evaluate the usefulness of pseudo-continuous arterial spin labeling (pCASL) imaging in differentiating high-grade gliomas from lymphomas and in noninvasively predicting genetic biomarkers in high-grade gliomas. Twelve glioblastoma multiforme (GBM), 3 anaplastic astrocytoma (AA), 5 recurred GBM, and 9 lymphoma patients underwent conventional MR and pCASL imaging. On pCASL perfusion map, mean absolute tumor blood flow (mTBF) was calculated from five regions of interest (ROIs) within the enhancing portion of the tumor. Relative TBF (rTBF = mTBF/mBFgm × 100) was also calculated. mTBF and rTBF of high-grade gliomas and lymphomas were compared using unpaired Student's t-test and receiver operating characteristic (ROC) analysis. Additionally, the association of TBF and six immunohistochemically confirmed genetic biomarkers was analyzed by Pearson correlation analysis in the group of high-grade gliomas. Both mTBF and rTBF of the high-grade gliomas were significantly higher than those of the lymphomas: 92.1 ± 34.7 versus 53.6 ± 30.5 mL/min/100 mg (P = 0.008) and 182.3 ± 69.5 versus 92.5 ± 44.9 (P = 0.002), respectively. Only epidermal growth factor receptor (EGFR) expression status showed a significant positive correlation with mTBF(P = 0.015) and rTBF(P = 0.007). pCASL imaging may facilitate differentiation of high-grade gliomas from lymphomas and prediction of EGFR expression status in high-grade gliomas. Copyright © 2013 Wiley Periodicals, Inc.

  1. Is less more? Comparing chemotherapy alone with chemotherapy and radiation for high-risk grade 2 glioma: An analysis of the National Cancer Data Base. (United States)

    Jhaveri, Jaymin; Liu, Yuan; Chowdhary, Mudit; Buchwald, Zachary S; Gillespie, Theresa W; Olson, Jeffrey J; Voloschin, Alfredo D; Eaton, Bree R; Shu, Hui-Kuo G; Crocker, Ian R; Curran, Walter J; Patel, Kirtesh R


    The addition of chemotherapy to adjuvant radiotherapy (chemotherapy and radiation therapy [CRT]) improves overall survival (OS) for patients with high-risk grade 2 gliomas; however, the impact of chemotherapy alone (CA) is unknown. This study compares the OS of patients with high-risk grade 2 gliomas treated with CA versus CRT. Patients with high-risk grade 2 gliomas (subtotal resection or age ≥ 40 years) with oligodendrogliomas, astrocytomas, or mixed tumors were identified with the National Cancer Data Base. Patients were grouped into CA and CRT cohorts. Univariate analyses and multivariate analyses (MVAs) were performed. Propensity score (PS) matching was also implemented. The Kaplan-Meier method was used to analyze OS. A total of 1054 patients with high-risk grade 2 gliomas were identified: 496 (47.1%) received CA, and 558 (52.9%) received CRT. Patients treated with CA were more likely (all P values  6 cm, astrocytoma histology, and older age were predictors for worse OS (all P values < .05). After 1:1 PS matching (n = 331 for each cohort), no OS difference was seen (P = .696) between the CA and CRT cohorts at 5 (69.3% vs 67.4%) and 8 years (52.8% vs 56.7%). No long-term OS difference was seen in patients with high-risk grade 2 gliomas treated with CA versus CRT. These findings are hypothesis-generating, and prospective clinical trials comparing these treatment paradigms are warranted. Cancer 2017. © 2017 American Cancer Society. © 2017 American Cancer Society.

  2. Metal recovery from high-grade WEEE

    DEFF Research Database (Denmark)

    Bigum, Marianne; Brogaard, Line Kai-Sørensen; Christensen, Thomas Højlund


    Based on available data in the literature the recovery of aluminium, copper, gold, iron, nickel, palladium and silver from high-grade WEEE was modeled by LCA. The pre-treatment of WEEE included manual sorting, shredding, magnetic sorting, Eddy-current sorting, air classification and optical sorting...... and refining of ore. The resource recovery per tonne of high-grade WEEE ranged from 2 g of palladium to 386 kg of iron. Quantified in terms of person-equivalents the recovery of palladium, gold, silver, nickel and copper constituted the major environmental benefit of the recovery of metals from WEEE...... effect compared to the metallurgical treatment. However only 12-26% of silver, gold and palladium are recovered during pre-treatment, which suggest that the reduction of the apparent losses of precious metals as palladium, gold and silver during pre-treatment of WEEE is of environmental importance. Our...

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


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


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

  4. Low-grade and high-grade endometrial stromal sarcoma: A National Cancer Database study. (United States)

    Seagle, Brandon-Luke L; Shilpi, Arunima; Buchanan, Samuel; Goodman, Chelain; Shahabi, Shohreh


    To provide refined prognostic information from large cohorts of women with low-grade or high-grade endometrial stromal sarcoma (ESS). We performed an observational retrospective cohort analysis of women diagnosed with low-grade or high-grade ESS from the 1998-2013 National Cancer Database. Kaplan-Meier and multivariable accelerated failure time survival analyses were performed to identify prognostic factors after multiple imputation of missing data. Recursive partitioning methods were used to rank prognostic factors in high-grade ESS. Matched cohort analyses were performed to hypothesis-test effects of adjuvant treatments. We identified 2414 and 1383 women with low-grade or high-grade ESS, respectively. Women with high-grade ESS had markedly decreased survival compared to women with low-grade ESS (five-year survival (95% CI): 32.6 (30.1-35.3%) versus 90.5% (89.3-91.8%), P<0.001). Among women with high-grade ESS, median survival (95% CI) was only 19.9 (17.1-22.1) months. Increased age and tumor size were associated with decreased survival in low-grade ESS. In high-grade ESS, additional negative prognostic factors were distant or nodal metastasis, omission of lymphadenectomy, and pathologically-positive surgical margins (all P<0.001). Use of adjuvant chemotherapy (time ratio (TR) (95% CI): 1.36 (1.17-1.58), P<0.001) and radiotherapy (TR (95% CI): 1.57 (1.32-1.87), P<0.001) were associated with increased survival for high-grade ESS. The contrasting excellent versus poor prognosis of low-grade versus high-grade ESS, respectively, was confirmed. The best treatment of high-grade ESS is early and complete surgical resection including lymphadenectomy. Adjuvant chemotherapy and radiotherapy may increase survival of women with high-grade ESS. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    DEFF Research Database (Denmark)

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


    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...

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

    NARCIS (Netherlands)

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

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

  7. Spinal Cord Astrocytoma with Isocitrate Dehydrogenase 1 Gene Mutation. (United States)

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


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

  8. Astrocytoma (United States)

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

  9. miR-137 acts as a tumor suppressor in astrocytoma by targeting RASGRF1. (United States)

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


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

  10. The relationship between polymorphisms of XRCC5 genes with astrocytoma prognosis in the Han Chinese population (United States)

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


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

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

    Directory of Open Access Journals (Sweden)

    Cléciton Braga Tavares

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

  12. MRI differentiation of low-grade from high-grade appendicular chondrosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Douis, Hassan; Singh, Leanne; Saifuddin, Asif [The Royal National Orthopaedic Hospital NHS Trust, Department of Radiology, Stanmore, Middlesex (United Kingdom)


    To identify magnetic resonance imaging (MRI) features which differentiate low-grade chondral lesions (atypical cartilaginous tumours/grade 1 chondrosarcoma) from high-grade chondrosarcomas (grade 2, grade 3 and dedifferentiated chondrosarcoma) of the major long bones. We identified all patients treated for central atypical cartilaginous tumours and central chondrosarcoma of major long bones (humerus, femur, tibia) over a 13-year period. The MRI studies were assessed for the following features: bone marrow oedema, soft tissue oedema, bone expansion, cortical thickening, cortical destruction, active periostitis, soft tissue mass and tumour length. The MRI-features were compared with the histopathological tumour grading using univariate, multivariate logistic regression and receiver operating characteristic curve (ROC) analyses. One hundred and seventy-nine tumours were included in this retrospective study. There were 28 atypical cartilaginous tumours, 79 grade 1 chondrosarcomas, 36 grade 2 chondrosarcomas, 13 grade 3 chondrosarcomas and 23 dedifferentiated chondrosarcomas. Multivariate analysis demonstrated that bone expansion (P = 0.001), active periostitis (P = 0.001), soft tissue mass (P < 0.001) and tumour length (P < 0.001) were statistically significant differentiating factors between low-grade and high-grade chondral lesions with an area under the ROC curve of 0.956. On MRI, bone expansion, active periostitis, soft tissue mass and tumour length can reliably differentiate high-grade chondrosarcomas from low-grade chondral lesions of the major long bones. (orig.)

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

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


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

  14. Intraoperative squash cytologic features of subependymal giant cell astrocytoma

    Directory of Open Access Journals (Sweden)

    Jitendra Nasit


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

  15. Intraoperative Squash Cytologic Features of Subependymal Giant Cell Astrocytoma. (United States)

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


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

  16. High-grade primary pulmonary leiomyosarcoma

    Directory of Open Access Journals (Sweden)

    Rodrigo Afonso da Silva Sardenberg


    Full Text Available Primary sarcomas of the lung are rare and account for 0.5% of all primary lung tumors. There were approximately 300 cases described in the literature as of 2006. All histologic types of sarcoma were described, and the most common intrathoracic types reported were angiosarcoma, leiomyosarcoma, fibrosarcoma, hemangiopericytoma, and rhabdomyosarcoma. The biological behavior of these tumors is not well-known due to their low frequency. Leiomyosarcomas represent one of the most common subtypes encountered in the lungs, and usually occur during the sixth decade, with male predominance. Although the frequency of metastatic disease is not related to tumor size, prognosis was reported to be poorer in high-grade tumors. In comparison with other sarcomas, survival after complete resection of pulmonary leiomyosarcoma was reported as longer. We report on a patient with primary leiomyosarcoma originating from the bronchus with complete resection and long-term follow-up.

  17. Posterior surgery in high-grade spondylolisthesis. (United States)

    Lengert, R; Charles, Y P; Walter, A; Schuller, S; Godet, J; Steib, J-P


    High-grade L5-S1 spondylolisthesis alters sagittal spinopelvic balance, which can cause low back pain and progressive neurologic disorder. The present study assessed spondylolisthesis reduction and maintenance over time with L4-S1 versus L5-S1 fusion using a lever-arm system and posterior fusion combined with lumbosacral graft. Forty patients were operated on for symptomatic high-grade spondylolisthesis, 34 of whom had full pre- and post-operative radiological analysis, with a mean follow-up of 5.4years. There were 9 L5-S1 and 25 L4-S1 instrumentations. Analysis of spinopelvic and slipping parameters and the evolution of segmental lordosis compared results between L5-S1 and L4-S1 instrumentation. Mean Taillard spondylolisthesis index decreased from 64% to 37% (P=0.0001). Overall sagittal spinopelvic balance was not significantly changed. Overall L1-S1 and segmental L4-L5 lordosis were not affected by instrumentation. Mean L5-S1 segmental lordosis increased from 11° to 18°. There was loss of reduction from 19° to 14° with L5-S1 instrumentation, in contrast to maintained reduction with L4-S1 instrumentation (P=0.006). The lever-arm system provided anterior-posterior reduction of spondylolisthesis and corrected slippage. Postoperative change in overall sagittal spinopelvic balance was slight and constant. Posterior L4-S1 fusion provided better long-term control of L5-S1 lordosis reduction than the shorter L5-S1 fusion. Retrospective study of level IV. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  18. Exploratory Visual Analysis of Statistical Results from Microarray Experiments Comparing High and Low Grade Glioma

    Directory of Open Access Journals (Sweden)

    Jason H. Moore


    Full Text Available The biological interpretation of gene expression microarray results is a daunting challenge. For complex diseases such as cancer, wherein the body of published research is extensive, the incorporation of expert knowledge provides a useful analytical framework. We have previously developed the Exploratory Visual Analysis (EVA software for exploring data analysis results in the context of annotation information about each gene, as well as biologically relevant groups of genes. We present EVA as a fl exible combination of statistics and biological annotation that provides a straightforward visual interface for the interpretation of microarray analyses of gene expression in the most commonly occurring class of brain tumors, glioma. We demonstrate the utility of EVA for the biological interpretation of statistical results by analyzing publicly available gene expression profi les of two important glial tumors. The results of a statistical comparison between 21 malignant, high-grade glioblastoma multiforme (GBM tumors and 19 indolent, low-grade pilocytic astrocytomas were analyzed using EVA. By using EVA to examine the results of a relatively simple statistical analysis, we were able to identify tumor class-specifi c gene expression patterns having both statistical and biological signifi cance. Our interactive analysis highlighted the potential importance of genes involved in cell cycle progression, proliferation, signaling, adhesion, migration, motility, and structure, as well as candidate gene loci on a region of Chromosome 7 that has been implicated in glioma. Because EVA does not require statistical or computational expertise and has the fl exibility to accommodate any type of statistical analysis, we anticipate EVA will prove a useful addition to the repertoire of computational methods used for microarray data analysis. EVA is available at no charge to academic users and can be found at

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

    Directory of Open Access Journals (Sweden)

    Roseli da Silva

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

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

    Directory of Open Access Journals (Sweden)

    Daniel Winardi


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

  1. [Clinical course of a solitary retinal astrocytoma]. (United States)

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


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

  2. Grades, Coursework, and Student Characteristics in High School Economics (United States)

    Rebeck, Ken; Walstad, William B.


    The authors use U.S. public and private high school transcripts to analyze grade distribution patterns in economics courses across student and school characteristics, and compare these grades to those earned in other selected high school courses. Results are reported for the 53 percent of 2009 high school graduates who took a basic economics…

  3. Bilateral Birdshot Retinochoroiditis and Retinal Astrocytoma (United States)

    Wong, Yun; Bell, Dugald


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

  4. Pilocytic Astrocytoma of the Optic Pathway: A Tumour Deriving from Radial Glia Cells with a Specific Gene Signature (United States)

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


    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…

  5. Fragile X mental retardation protein promotes astrocytoma proliferation via the MEK/ERK signaling pathway (United States)

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


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

  6. Elevated expression of HSP10 protein inhibits apoptosis and associates with poor prognosis of astrocytoma. (United States)

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


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

  7. Progesterone promotes cell migration, invasion and cofilin activation in human astrocytoma cells. (United States)

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


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

  8. Report of effective trametinib therapy in 2 children with progressive hypothalamic optic pathway pilocytic astrocytoma: documentation of volumetric response. (United States)

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


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

  9. Prognostic value of preoperative dynamic contrast-enhanced MRI perfusion parameters for high-grade glioma patients

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    Ulyte, Agne [Vilnius University, Faculty of Medicine, Vilnius (Lithuania); Katsaros, Vasileios K. [General Anticancer and Oncological Hospital ' ' St. Savvas' ' , Department of Advanced Imaging Modalities - CT and MRI, Athens (Greece); University of Athens, Department of Neurosurgery, Evangelismos Hospital, Athens (Greece); Liouta, Evangelia; Stranjalis, Georgios [University of Athens, Department of Neurosurgery, Evangelismos Hospital, Athens (Greece); Boskos, Christos [University of Athens, Department of Neurosurgery, Evangelismos Hospital, Athens (Greece); General Anticancer and Oncological Hospital ' ' St. Savvas' ' , Department of Radiation Oncology, Athens (Greece); Papanikolaou, Nickolas [Champalimaud Foundation, Department of Radiology, Centre for the Unknown, Lisbon (Portugal); Usinskiene, Jurgita [National Cancer Institute, Vilnius (Lithuania); Affidea Lietuva, Vilnius (Lithuania); Bisdas, Sotirios [University College London Hospitals, Department of Neuroradiology, The National Hospital for Neurology and Neurosurgery, London (United Kingdom)


    The prognostic value of the dynamic contrast-enhanced (DCE) MRI perfusion and its histogram analysis-derived metrics is not well established for high-grade glioma (HGG) patients. The aim of this prospective study was to investigate DCE perfusion transfer coefficient (K{sup trans}), vascular plasma volume fraction (v{sub p}), extracellular volume fraction (v{sub e}), reverse transfer constant (k{sub ep}), and initial area under gadolinium concentration time curve (IAUGC) as predictors of progression-free (PFS) and overall survival (OS) in HGG patients. Sixty-nine patients with suspected anaplastic astrocytoma or glioblastoma underwent preoperative DCE-MRI scans. DCE perfusion whole tumor region histogram parameters, clinical details, and PFS and OS data were obtained. Univariate, multivariate, and Kaplan-Meier survival analyses were conducted. Receiver operating characteristic (ROC) curve analysis was employed to identify perfusion parameters with the best differentiation performance. On univariate analysis, v{sub e} and skewness of v{sub p} had significant negative impacts, while k{sub ep} had significant positive impact on OS (P < 0.05). v{sub e} was also a negative predictor of PFS (P < 0.05). Patients with lower v{sub e} and IAUGC had longer median PFS and OS on Kaplan-Meier analysis (P < 0.05). K{sup trans} and v{sub e} could also differentiate grade III from IV gliomas (area under the curve 0.819 and 0.791, respectively). High v{sub e} is a consistent predictor of worse PFS and OS in HGG glioma patients. v{sub p} skewness and k{sub ep} are also predictive for OS. K{sup trans} and v{sub e} demonstrated the best diagnostic performance for differentiating grade III from IV gliomas. (orig.)

  10. Sports participation and high grade renal injuries in children. (United States)

    Gerstenbluth, Robert E; Spirnak, J Patrick; Elder, Jack S


    The risk of major renal injury resulting from various forms of sports participation is unknown. Urologists often recommend that children with a solitary kidney avoid contact sports. We reviewed our recent experience with pediatric renal trauma to determine if there is an association between different types of sports activity and high grade renal injury. We retrospectively reviewed the medical records of 68 consecutive children with blunt renal injury who were treated at 2 level I trauma centers. Injuries were graded using the renal injury scale of the American Association for the Surgery of Trauma. Records were reviewed for mechanism of injury, associated injuries, management and injury severity score. Statistical analysis was performed using Fisher's exact test or Wilcoxon rank sum test. Of the 68 renal lesions 13 were grade I, 15 grade II, 15 grade III, 17 grade IV and 8 grade V. The most common cause of renal trauma was motor vehicle accidents, accounting for 21 injuries (30.1%). Accidents associated with nonmotorized sports activity accounted for 14 injuries (20.6%). Bicycle riding was the most common sports etiology, accounting for 8 of 14 cases (57.1%) at an age range of 5 to 15 years (mean 9.4). None of the bicycle injuries involved collision with a motor vehicle. Bicycling accounted for 1 grade I, 1 grade II, 1 grade III, 2 grade IV and 3 grade V injuries. Football, hockey and sledding were responsible for the remaining 6 sports related injuries. High grade renal injury (grade IV or V) was identified in 5 of 8 bicycle accidents (62.5%) and 1 of 6 nonbicycle sports related injuries (16.7%, p = 0.14). Injury severity scores ranged from 4 to 50 (mean 20.6) for bicycle renal injuries and 4 to 13 (mean 6.7) for nonbicycle sports related trauma (p sports related cause of renal injury in children and is associated with a significant risk of major renal injury. Families of children with a solitary kidney should be aware of this risk factor. Team contact sports are

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

    NARCIS (Netherlands)

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


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

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


    Isaacs, Hart


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

  13. Effects of diphenylhydantoin on murine astrocytoma radiosensitivity

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


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

  14. Rapid progression to glioblastoma in a subset of IDH-mutated astrocytomas: a genome-wide analysis. (United States)

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


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

  15. 40 CFR 246.200 - High-grade paper recovery. (United States)


    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false High-grade paper recovery. 246.200 Section 246.200 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES SOURCE... paper recovery. ...

  16. Role of radiotherapy for high grade gliomas management. (United States)

    Caruso, C; Carcaterra, M; Donato, V


    We have analyzed the therapeutic standard options for high grade gliomas, with particular attention to the different radiation therapy modalities and techniques and their application considering the natural history of the disease. Of the several therapeutic options, surgical resection remains the initial treatment of choice for patients with high grade glioma; of all adjuvant treatments tested, radiotherapy offers the greatest magnitude of survival benefit, so radiotherapy, which must be started within 6 weeks of surgery, is mandatory for practically all patients with high grade gliomas. In this paper we perform an overview considering the integration between the different therapeutic modalities, with particular attention to the radiation therapy role in the management of high grade gliomas.

  17. Cognitive impairments in patients with low grade gliomas and high grade gliomas

    Directory of Open Access Journals (Sweden)

    Eliane C. Miotto


    Full Text Available OBJECTIVE: The relationship between brain tumors and cognitive deficits is well established in the literature. However, studies investigating the cognitive status in low and high-grade gliomas patients are scarce, particularly in patients with average or lower educational level. This study aimed at investigating the cognitive functioning in a sample of patients with low and high-grade gliomas before surgical intervention. METHOD: The low-grade (G1, n=19 and high-grade glioma (G2, n=8 patients underwent a detailed neuropsychological assessment of memory, executive functions, visuo-perceptive and visuo-spatial abilities, intellectual level and language. RESULTS: There was a significant impairment on verbal and visual episodic memory, executive functions including mental flexibility, nominal and categorical verbal fluency and speed of information processing in G2. G1 showed only specific deficits on verbal and visual memory recall, mental flexibility and processing speed. CONCLUSION: These findings demonstrated different levels of impairments in the executive and memory domains in patients with low and high grade gliomas.

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

    Directory of Open Access Journals (Sweden)

    Hafez Raef FA


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

  19. Traumatic high-grade cervical dislocation: treatment strategies and outcomes. (United States)

    Sribnick, Eric A; Hoh, Daniel J; Dhall, Sanjay S


    Traumatic high-grade cervical spinal dislocations are rare injuries, generally associated with severe neurological compromise. In particular, cervical spondyloptosis (>100% subluxation) is rarely reported. The object of our study is to present a case series describing presentation, management, and outcome in traumatic high-grade cervical spinal dislocations. Retrospective analysis was performed involving two level 1 trauma centers. Patients with a high-grade traumatic cervical subluxation were selected from a database, and these patients were admitted between August 2007 and July 2011. Fifteen patients were identified; three had spondyloptosis. The admission American Spinal Injury Association Impairment Scale (AIS) grade varied (A = 9; B = 2; C = 1; D = 2; E = 1). Fourteen patients underwent attempted closed reduction with six (43%) failing closed reduction. High-dose methylprednisolone was administered in nine patients (60%). All patients underwent surgical stabilization: three underwent anterior only, three underwent posterior only, and nine underwent a combined anterior-posterior approach. Postoperatively, one patient improved two AIS grades, three improved one AIS grade, nine maintained their preoperative score, and two patients worsened. In this series, 26.7% of patients had improvement in their AIS grade postoperatively, and the majority of patients (60%) maintained their preoperative AIS grade. In 57% of patients placed in traction, reduction was possible. Likely due to the severity of these injuries, there was a high incidence of complications. However, review of patient outcomes reveals that these patients can have improvement of neurological function. We recommend aggressive reduction and surgical stabilization. Our preference is either a combined anterior-posterior approach or a posterior-only approach. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. High grade leiomyosarcoma of the testes

    Directory of Open Access Journals (Sweden)

    Girish D. Bakhshi


    Full Text Available Testicular leiomyosarcoma is a rare tumor. It may arise secondarily following exposure to radiotherapy, chronic inflammation, or usage of high dose anabolic steroids. However, in absence of risk factors, it is rarely seen. Only 15 cases of Primary Intra testicular leiomyosarcoma have been reported in world literature. We present a case of testicular tumor in an elderly male. Preoperative work up showed raised Lactate Dehydrogenase (LDH levels. He underwent high orchidectomy. Histopathology and immunohistochemistry confirmed it to be a primary intra testicular leiomyosarcoma. A brief case report with review of literature is presented.

  1. Radiologic Dilemma in an Extra-Axial Petroclival Lesion: Low Grade versus High Grade. (United States)

    Karthigeyan, Madhivanan; Ahuja, Chirag Kamal; Chatterjee, Debjyoti; Salunke, Pravin


    Radiologic differentiation between a low-grade and high-grade lesion is crucial when deciding extent of resection and prognostication. Occasionally, imaging features can be confusing between the 2 lesions. We report a case that presented such a radiologic dilemma. The lesion appeared benign and extra-axial on routine magnetic resonance imaging sequences. However, subtle clinical and imaging clues pointed to a high-grade lesion. A 27-year-old woman presented with multiple cranial nerve palsies, gait ataxia, and features of increased intracranial pressure. Computed tomography and magnetic resonance imaging showed a petroclival extra-axial contrast-enhancing lesion with areas of chunky calcification. Although choline peak on spectroscopy raised suspicion of a high-grade lesion, the primary differential diagnosis included meningioma and schwannoma considering its characteristic imaging appearance. Postoperative histopathology showed the lesion to be giant cell glioblastoma. Apart from reporting a rare variant of glioblastoma in an unusual location, this case highlights atypical imaging in a glioblastoma. Brainstem edema may be a subtle indicator of the infiltrative nature of a tumor. Magnetic resonance spectroscopy may be a useful adjunct in such circumstances. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Phase II Trial of Erlotinib during and after Radiotherapy in Children with Newly Diagnosed High-Grade Gliomas

    Directory of Open Access Journals (Sweden)

    Ibrahim eQaddoumi


    Full Text Available Background. Epidermal growth factor receptor is overexpressed in most pediatric high-grade gliomas (HGG. Since erlotinib had shown activity in adults with HGG, we conducted a phase II trial of erlotinib and local radiotherapy in children with newly diagnosed HGG. Methods. Following maximum surgical resection, patients between 3 and 21 years with nonmetastatic HGG received local radiotherapy at 59.4 Gy (54 Gy for spinal tumors and those with ≥70% brain involvement. Erlotinib started on day 1 of radiotherapy (120 mg/m2 per day and continued for 2 years unless there was tumor progression or intolerable toxicities. The 2-year progression-free survival (PFS was estimated for patients with intracranial anaplastic astrocytoma (AA and glioblastoma.Results. Median age at diagnosis for 41 patients with intracranial tumors (21 with glioblastoma and 20 with AA was 10.9 years (range, 3.3 to 19 years. The 2-year PFS for patients with AA and glioblastoma was 15% ± 7% and 19% ± 8%, respectively. Only five patients remained alive without tumor progression. Twenty-six patients had at least one grade 3 or 4 toxicity irrespective of association with erlotinib; only four required dose modifications. The main toxicities were gastrointestinal (n=11, dermatologic (n=5, and metabolic (n=4. One patient with gliomatosis cerebri who required prolonged corticosteroids died of septic shock associated with pancreatitis. Conclusions. Although therapy with erlotinib was mostly well tolerated, it did not change the poor outcome of our patients. Our results showed that erlotinib is not a promising medication in the treatment of children with intracranial AA and glioblastoma.

  3. An Achilles tendinosis masking an intramedullary astrocytoma. (United States)

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


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

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

    Directory of Open Access Journals (Sweden)

    Eiron Cudaback


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


    Glavatskyi, O.; Buryk, V.M.; Kardash, K.A.; Pylypas, O.P.; Chebotaryova, T.I.


    respectively. CONCLUSIONS: Hypofractionated stereotactic radiosurgery is one of possible treatment options for high-grade gliomas which leads to a decrease in tumor volume and improves clinical status of patients even in cases of re-irradiation. Surgical treatment after radiosurgery doesn't worsen median overall survival and progression free survival prognosis.

  6. Successful Nonoperative Management of High-Grade Blunt Renal Injuries. (United States)

    May, Allison M; Darwish, Oussama; Dang, Brian; Monda, John J; Adsul, Prajakta; Syed, Johar; Siddiqui, Sameer A


    Current management of high-grade blunt renal trauma favors a nonoperative approach when possible. We performed a retrospective study of high grade blunt renal injuries at our level I trauma center to determine the indications and success of nonoperative management (NOM). 47 patients with blunt grade IV or V injuries were identified between October 2004 and December 2013. Immediate operative patients (IO) were compared to nonoperatively managed (NOM). Of the 47 patients, 3 (6.4%) were IO and 44 (95.6%) NOM. IO patients had a higher heart rate on admission, 133 versus 100 in NOM ( P = 0.01). IO patients had a higher rate of injury to the renal vein or artery (100%) compared to NOM group (18%) ( P = 0.01). NOM failed in 3 of 44 patients (6.8%). Two required nonemergent nephrectomy and one required emergent exploration resulting in nephrectomy. Six NOM patients had kidney-related complications (13.6%). The renal salvage rate for the entire cohort was 87.2% and 93.2% for NOM. Nonoperative management for hemodynamically stable patients with high-grade blunt renal trauma is safe with a low risk of complications. Management decisions should consider hemodynamic status and visualization of active renal bleeding as well as injury grade in determining operative management.

  7. Elective neck management for high-grade salivary gland carcinoma. (United States)

    Herman, Michael P; Werning, John W; Morris, Christopher G; Kirwan, Jessica M; Amdur, Robert J; Mendenhall, William M


    To determine whether patients with clinically node negative (cNo) high grade salivary gland carcinomas benefit from an elective neck dissection prior to postoperative radiotherapy (RT). Between October 1964 and October 2009, 59 previously untreated patients with cNo high-grade salivary gland carcinomas (squamous cell carcinomas were excluded) were treated with curative intent using elective neck dissection (END; n=41), or elective neck irradiation (ENI; n=18) at the University of Florida College of Medicine (Gainesville, FL). All patients underwent resection of the primary cancer followed by postoperative RT. The median follow-up period was 5.2years (range, 0.3-34years). Occult metastases were found in 18 (44%) of the 41 patients in the END group. There were 4 recurrences (10%) in the END group and 0 recurrence in the ENI group. Neck control rates at 5years were: END, 90%; ENI, 100%; and overall, 93% (p=0.1879). Cause-specific survival was 94% in the ENI group, 84% in the END group, and 86% for all patients (p=0.6998). There were 3 reported grade 3 or 4 toxicities. Two patients had a postoperative fistula and one patient had a grade 4 osteoradionecrosis that required a partial mandibulectomy. Patients with cNo high grade salivary gland carcinomas who are planned to undergo surgery and postoperative RT likely do not benefit from a planned neck dissection. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Combination of AQP1 and β-catenin expression is an independent prognosis factor in astrocytoma patients (United States)

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


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

  9. Comparison and correlation of pelvic parameters between low-grade and high-grade spondylolisthesis. (United States)

    Min, Woo-Kie; Lee, Chang-Hwa


    This study was retrospectively conducted on 51 patients with L5-S1 spondylolisthesis. This study was conducted to compare a total of 11 pelvic parameters, such as the level of displacement by Meyerding method, lumbar lordosis, sacral inclination, lumbosacral angle, slip angle, S2 inclination, pelvic incidence (PI), L5 inclination, L5 slope, pelvic tilt (PT), and sacral slope (SS) between low-grade and high-grade spondylolisthesis, and to investigate a correlation of the level of displacement by Meyerding method with other pelvic parameters. Pelvic parameters were measured using preoperational erect lateral spinal simple radiographs. The patients were divided into 39 patients with low-grade spondylolisthesis and 12 patients with high-grade spondylolisthesis before analysis. In all patients of both groups, 11 radiographic measurements including the level of displacement by Meyerding method, lumbar lordosis, sacral inclination, lumbosacral angle, slip angle, S2 inclination, PI, L5 inclination, L5 slope, PT, and SS were performed. T test and Pearson correlation analysis were conducted to compare and analyze each measurement. As for the comparison between the 2 groups, a statistically great significance in the level of displacement by Meyerding method, lumbosacral angle, slip angle, L5 incidence, PI, and L5 slope (P≤0.001) was shown. Meanwhile, a statistical significance in the sacral inclination and PT (Pspondylolisthesis and patients with low-grade spondylolisthesis. Among the aforementioned measurements, the PI showed a significant difference between the 2 groups and also had a significant correlation with the dislocation level in all the patients.

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


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

  11. Functionally graded materials produced with high power lasers

    NARCIS (Netherlands)

    De Hosson, JTM; Ocelík, Vašek; Chandra, T; Torralba, JM; Sakai, T


    In this keynote paper two examples will be present of functionally graded materials produced with high power Nd:YAG lasers. In particular the conditions for a successful Laser Melt Injection (LMI) of SiC and WC particles into the melt pool of A18Si and Ti6Al4V alloys are presented. The formation of

  12. BRAF V600E mutations are frequent in dysembryoplastic neuroepithelial tumors and subependymal giant cell astrocytomas. (United States)

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


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

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

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


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

  14. Atypical imaging in a desmoplastic non-infantile astrocytoma. (United States)

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


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

  15. A comprehensive review of paediatric low-grade diffuse glioma: pathology, molecular genetics and treatment. (United States)

    Ryall, Scott; Tabori, Uri; Hawkins, Cynthia


    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.

  16. High Grade Myofibroblastic Sarcoma of Paratesticular Soft Tissues

    Directory of Open Access Journals (Sweden)

    Ioannis Anastasiou


    Full Text Available Tumors of the paratesticular region most often arise from the soft tissue surrounding the spermatic cord and the epididymis or from the soft tissue (dartos muscle of the scrotal wall. Paratesticular tumors, despite their rarity, present a high incidence of malignancy (30%, and the therapeutic approach of choice is surgical resection with negative margin. The grade, the histology type, the presence of metastases during the diagnosis, the size of the tumor, the age of the patients, and the surgical margins are all important prognostic factors. We present a case report of a 86-year-old patient with a high grade paratesticular and scrotum sarcoma of soft tissues which was presented as a hard painful mass of the scrotum. The patient was subjected to high ligation of the spermatic cord and received no further treatment and 6 months after the operation no local or systematic recurrence was observed.

  17. High grade leiomyosarcoma mimicking a recurrent angiomyxoma in the perineum

    Directory of Open Access Journals (Sweden)

    Neha Sood


    Full Text Available Perineal leiomyosarcoma is an extremely rare and aggressive cancer with a high metastatic potential and no defined standard treatment. There are only a few (six reported cases in the literature. We report the case of a 67-year-old woman with a perineal leiomyosarcoma arising at the same site of a previously resected superficial angiomyxoma. Initially, she was treated for a presumptive recurrence of angiomyxoma. As she did not respond to medical therapy, she underwent repeat surgical excision. Pathology revealed a high grade leiomyosarcoma, histologically strikingly distinct from the initial diagnosis. She received adjuvant local radiation therapy, and remains without evidence of recurrent disease 36 months after completion of all therapy. This is the first reported case of a high grade perineal leiomyosarcoma originating at the same site as a resected benign superficial angiomyxoma. Our case emphasizes the necessity of a prompt histological diagnosis in cases of presumed recurrent perineal angiomyxoma.

  18. Molecular events leading to HPV-induced high grade neoplasia

    Directory of Open Access Journals (Sweden)

    Saskia M. Wilting


    Full Text Available Cervical cancer is initiated by high-risk types of the human papillomavirus (hrHPV and develops via precursor stages, called cervical intraepithelial neoplasia (CIN. High-grade CIN lesions are considered true precancerous lesions when the viral oncogenes E6 and E7 are aberrantly expressed in the dividing cells. This results in abolishment of normal cell cycle control via p53 and pRb degradation. However, it has become clear that these viral oncogenes possess additional oncogenic properties, including interference with the DNA methylation machinery and mitotic checkpoints. Identification of the resulting molecular events leading to high-grade neoplasia will 1 increase our understanding of cervical carcinogenesis, 2 yield biomarkers for early diagnosis, and 3 identify therapeutic targets for HPV-induced (pre cancerous lesions.This review will briefly summarise current advances in our understanding of the molecular alterations in the host cell genome that occur during HPV-induced carcinogenesis.

  19. Promotion of astrocytoma cell invasion by micro RNA-22 targeting of tissue inhibitor of matrix metalloproteinase-2. (United States)

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


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

  20. Extracranial bone metastases from recurrent anaplastic astrocytoma on FDG PET/CT: A case report a care-compliant article. (United States)

    Li, Zu-Gui; Mu, Hai-Yu


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

  1. Postoperative surveillance of pediatric cerebellar pilocytic astrocytoma. (United States)

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


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

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

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


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

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

    African Journals Online (AJOL)

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

  4. Intermediate pilomyxoid astrocytoma and diencephalic syndrome: imaging findings

    Directory of Open Access Journals (Sweden)

    Olavo Kyosen Nakamura


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

  5. Cytologic characteristics of subependymal giant cell astrocytoma in squash smears: morphometric comparisons with gemistocytic astrocytoma and giant cell glioblastoma. (United States)

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


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

  6. High-grade surface osteosarcoma of the hand

    Energy Technology Data Exchange (ETDEWEB)

    Abe, Kuniko; Hayashi, Tomayoshi; Kinoshita, Naoe [Nagasaki University Hospital, Department of Pathology, Nagasaki (Japan); Kumagai, Kenji; Shindo, Hiroyuki [Nagasaki University Graduate School of Biomedical Sciences, Department of Orthopedic Surgery, Nagasaki (Japan); Uetani, Masataka [Nagasaki University Graduate School of Biomedical Sciences, Department of Radiology and Radiation Biology, Nagasaki (Japan); Ishida, Tsuyoshi [National Center of Neurology and Psychiatry, Department of Pathology and Laboratory Medicine, Kohnodai Hospital, Chiba (Japan); Tokyo Medical and Dental University, Department of Molecular Bone and Cartilage Pathology, Hard Tissue Genome Research Center, Tokyo (Japan)


    A 32-year-old woman presented with a 1-year history of mild pain in the right ring finger. Radiographs and CT revealed a calcified lesion with cortical erosion on the surface of the proximal aspect of the right ring finger proximal phalanx. On magnetic resonance imaging (MRI), the lesion showed low signal intensity on T1- and T2-weighted images and slight enhancement with gadolinium. Clinically, it was diagnosed as a benign bone-forming lesion such as florid reactive periostitis, and excision was accordingly performed. However, histological examination revealed proliferation of atypical osteoblastic cells among irregularly arranged osteoid seams. Taking the imaging findings into account, a pathological diagnosis of high-grade surface osteosarcoma was established. In general, bone- and cartilage-forming lesions of the hands and feet are benign. Osteosarcoma of short tubular bones in the hands and feet is extremely rare; moreover, high-grade surface osteosarcoma is one of the rarest subtypes of osteosarcoma. Nonetheless, high-grade surface osteosarcoma should be included in the differential diagnosis, particularly if the radiological findings or clinical course are not entirely typical of a more common benign process, to avoid incorrect clinicoradiological and pathological diagnosis. (orig.)

  7. Early genetic changes involved in low-grade astrocytic tumor development. (United States)

    Arjona, Dolores; Rey, Juan Antonio; Taylor, Shirley M


    Astrocytomas represent the most common form of glial tumors. The most malignant grade of these tumors, glioblastoma multiforme, may arise as a malignant progression from low-grade astrocytoma through anaplastic astrocytoma to secondary GBM, or else it may arise "de novo" as primary GBM. Both types of glioblastoma are usually histologically indistinguishable. However, distinct molecular alterations have been described between them that potentially allow differentiation between the two mechanisms of origin. Since malignant transformation is a multistep process, we summarize in this review the earliest genetic changes that seem to be involved in the appearance and development of low-grade astrocytic tumors, where early detection and treatment could be possible.

  8. CASC2c as an unfavorable prognosis factor interacts with miR-101 to mediate astrocytoma tumorigenesis. (United States)

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


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

  9. A survival analysis comparing women with ovarian low-grade serous carcinoma to those with high-grade histology

    Directory of Open Access Journals (Sweden)

    Chen M


    Full Text Available Ming Chen,1 Ying Jin,1 Yalan Bi,2 Jie Yin,1 Yongxue Wang,1 Lingya Pan1 1Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China; 2Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China Abstract: Ovarian low-grade serous carcinoma (LGSC and high-grade serous carcinoma have distinct molecular profiles, clinical behaviors, and treatment responses. The survival advantage for patients with low-grade carcinoma compared with patients with high-grade histology remains controversial. We retrospectively reviewed the medical charts of 381 patients with ovarian serous carcinoma at Peking Union Medical College Hospital from 2007 to 2010. Patients were classified into two groups according to MD Anderson two-tier system: 35 (9.2% cases with LGSC and 346 with high-grade serous carcinoma. Patients with low-grade serous ovarian cancer had a significantly younger age at diagnosis (46 versus 56 years, P=0.046, and their median progression-free survival (PFS and overall survival values were 35.0 and 54.0 months, respectively. A multivariate analysis showed that, for serous ovarian cancer, the histological grade was a significant prognostic factor for PFS but not for overall survival (P=0.022 and P=0.0566, respectively. When stratified by the existence of a residual disease, patients with low-grade disease who underwent cytoreductive surgery without macroscopic residual disease (>1 cm had a significantly improved median PFS time (36.0 months compared with that of patients with high-grade carcinoma who received optimal cytoreductive surgery (16.0 months, P=0.017. Conversely, patients with low-grade and high-grade carcinoma who were left with macroscopic residue (>1 cm experienced a similarly shorter median PFS (10.0 and 13

  10. Biomechanics of high-grade spondylolisthesis with and without reduction. (United States)

    Wang, Wenhai; Aubin, Carl-Eric; Cahill, Patrick; Baran, George; Arnoux, Pierre-Jean; Parent, Stefan; Labelle, Hubert


    The clinical advantages of reducing spondylolisthesis over fusion in situ have several intuitive reasons such as restore the spinal column into a more anatomic relationship and alignment. However, there is only little evidence in the literature supporting the theoretical advantages of reduction, and its effect on spinopelvic alignment remains poorly defined. In this study, a comprehensive finite element model was developed to analyze the biomechanics of the spine after spinal fusion at L5-S1 in both types of high-grade spondylolisthesis (balanced and unbalanced pelvis). The relevant clinical indices (i.e. spondylolisthesis grade and Dubousset lumbosacral angle), the displacement of L4-L5, pressure within the annulus and nucleus, and stress at L4-L5 were evaluated and compared. The model can well predict the changes of the important clinical indices during the surgery. For a balanced pelvis, the reduction has a minimal effect on the biomechanical conditions at the adjacent level during postsurgical activities. In the unbalanced case, reduction induced larger deformation in the lumbosacral region and a higher stress concentration at adjacent level. Whether such a stress concentration can lead to long-term disc degeneration is not known. The results provide additional information for the clinician considering reduction of high-grade spondylolisthesis.

  11. MR imaging of brain pilocytic astrocytoma: beyond the stereotype of benign astrocytoma. (United States)

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


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

  12. MicroRNA-132 targets PEA-15 and suppresses the progression of astrocytoma in vitro. (United States)

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


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

  13. Differentiating high-grade from low-grade chondrosarcoma with MR imaging

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    Yoo, Hye Jin; Hong, Sung Hwan; Choi, Ja-Young; Choi, Jung-Ah; Kang, Heung Sik [Seoul National University College of Medicine, Department of Radiology and Institute of Radiation Medicine, Seoul (Korea); Moon, Kyung Chul [Seoul National University College of Medicine, Department of Pathology, Seoul (Korea); Kim, Han-Soo [Seoul National University College of Medicine, Department of Orthopedic Surgery, Seoul (Korea)


    The purpose of the study was to evaluate the MR imaging features that differentiate between low-grade chondrosarcoma (LGCS) and high-grade chondrosarcoma (HGCS) and to determine the most reliable predictors for differentiation. MR images of 42 pathologically proven chondrosarcomas (28 LGCS and 14 HGCS) were retrospectively reviewed. There were 13 male and 29 female patients with an age range of 23-72 years (average age 51 years). On MR images, signal intensity, specific morphological characteristics including entrapped fat, internal lobular architecture, and outer lobular margin, soft tissue mass formation and contrast enhancement pattern were analysed. MR imaging features used to identify LGCS and HGCS were compared using univariate analysis and multivariate stepwise logistic regression analysis. On T1-weighted images, a central area of high signal intensity, which was not seen in LGCS, was frequently observed in HGCS (n = 5, 36%) (p < 0.01). Entrapped fat within the tumour was commonly seen in LGCS (n = 26, 93%), but not in HGCS (n = 1, 4%) (p < 0.01). LGCS more commonly (n = 24, 86%) preserved the characteristic internal lobular structures within the tumour than HGCSs (n = 4, 29%) (p < 0.01). Soft tissue formation was more frequently observed in HGCS (n = 11, 79%) than in LGCS (n = 1, 4%) (p < 0.01). On gadolinium-enhanced images, large central nonenhancing areas were exhibited in only two (7.1%) of LGCS, while HGCS frequently (n = 9, 64%) had a central nonenhancing portion (p < 0.01). Results of multivariate stepwise logistic regression analysis showed that soft tissue formation and entrapped fat within the tumour were the variables that could be used to independently differentiate LGCS from HGCS. There were several MR imaging features of chondrosarcoma that could be helpful in distinguishing HGCS from LGCS. Among them, soft tissue mass formation favoured the diagnosis of HGCS, and entrapped fat within the tumour was highly indicative of LGCS. (orig.)

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

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    Sang Y Lee

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

  15. Histological outcomes of anal high-grade cytopredictions. (United States)

    Roberts, Jennifer Margaret; Jin, Fengyi; Poynten, Isobel Mary; Law, Carmella; Templeton, David James; Thurloe, Julia Kathleen; Garland, Suzanne Marie; Grulich, Andrew Edwin; Farnsworth, Annabelle; Hillman, Richard John


    Longitudinal studies of histological outcomes after anal cytological screening in men who have sex with men (MSM) are rare. This study measured the positive predictive values (PPVs) of each level of baseline cytological abnormality in MSM in Sydney, Australia, over a 12-month period. The Study of the Prevention of Anal Cancer is a 3-year prospective study of the natural history of anal human papillomavirus infection in MSM at least 35 years old. For each participant with a baseline cytological abnormality, the worst histology was recorded at the baseline high-resolution anoscopy and at 6 and 12 months. PPVs for a histological high-grade squamous intraepithelial lesion (HSIL) diagnosis were calculated for each level of baseline cytological abnormality at each time point. Among 424 men who completed 3 visits, the PPV of a cytological HSIL increased from 71.6% at the baseline to 86.4% at 6 months and to 92.6% at 12 months (P < .001). For cytological atypical squamous cells, cannot rule out high-grade squamous intraepithelial lesion (ASC-H), the PPV increased from 51.5% at the baseline to 69.7% at 6 months and to 75.8% at 12 months (P = .004). At each time point, the PPV of a cytological HSIL was significantly higher than the PPV of ASC-H. The PPV of low-grade cytology reports was significantly lower than the PPV of ASC-H at each time point. In a cohort of MSM, a baseline histological HSIL diagnosis after an HSIL cytoprediction is high, and it increases with further examinations over the course of 12 months. Lower levels of cytological abnormalities have significantly lower PPVs. These data can inform patient management and the quality assessment of each aspect of the screening pathway. Cancer Cytopathol 2017. © 2017 American Cancer Society. © 2017 American Cancer Society.

  16. 18F-FDOPA PET/CT or PET/MRI in Measuring Tumors in Patients With Newly-Diagnosed or Recurrent Gliomas (United States)


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

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


    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

  18. The emerging role of m-TOR up-regulation in brain Astrocytoma. (United States)

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


    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.

  19. Deciphering fluid inclusions in high-grade rocks

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    Alfons van den Kerkhof


    Full Text Available The study of fluid inclusions in high-grade rocks is especially challenging as the host minerals have been normally subjected to deformation, recrystallization and fluid-rock interaction so that primary inclusions, formed at the peak of metamorphism are rare. The larger part of the fluid inclusions found in metamorphic minerals is typically modified during uplift. These late processes may strongly disguise the characteristics of the “original” peak metamorphic fluid. A detailed microstructural analysis of the host minerals, notably quartz, is therefore indispensable for a proper interpretation of fluid inclusions. Cathodoluminescence (CL techniques combined with trace element analysis of quartz (EPMA, LA-ICPMS have shown to be very helpful in deciphering the rock-fluid evolution. Whereas high-grade metamorphic quartz may have relatively high contents of trace elements like Ti and Al, low-temperature re-equilibrated quartz typically shows reduced trace element concentrations. The resulting microstructures in CL can be basically distinguished in diffusion patterns (along microfractures and grain boundaries, and secondary quartz formed by dissolution-reprecipitation. Most of these textures are formed during retrograde fluid-controlled processes between ca. 220 and 500 °C, i.e. the range of semi-brittle deformation (greenschist-facies and can be correlated with the fluid inclusions. In this way modified and re-trapped fluids can be identified, even when there are no optical features observed under the microscope.

  20. CIGB-128, as compassionate intracranial treatment in patients with non-operable or progressive high grade gliomas

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    Garcia-Vega Y


    Full Text Available Background: High grade glioma (HGG is the most aggressive and lethal primary brain tumor. The treatment of patients with HGG still remains palliative with improvement in the quality of life and encompasses surgery, radiotherapy, and chemotherapy. The use of interferons (IFNs in the treatment of HGG has been showed useful for these patients. Patients and methods: We report the use, outside of clinical trials, of recombinant IFNs-α and γ(CIGB-128 in 10 patients with glioma grade III-IV (1 anaplastic astrocytoma and 9 GBM. The aim of the study was to offer a treatment option to patients with malignant gliomas, primary (non-surgical or progressive (Karnofsky performance status (KPS >20, without other possible therapeutic options, and non-eligible for clinical trials. Patients received intralesional CIGB-128, 3 times per week, during one month, in doses from 3.5 MIU scalable up to 14.0 MIU. Safety was evaluated by the occurrence of adverse events. Others measurements were tumor responses measured by RECIST, KPS, muscular power (ASIA neurological assessment scale and overall survival. Depending of treatment tolerability, clinical improvement and medical criteria, patients were maintained under treatment for 3 more months. Results: 70% of treated patients had KS<50. Seven patients had objective response (3 CR, 4 PR, one lesion progressed and 2 were not evaluable. The treatment prolonged the survival of patients to a mean of 34±14 months since diagnosis. The quality of life improved as measured by the increase in the KPS (66% of patients scaled the category and improvement in muscular power in 50% of patients. CIGB-128 had an acceptable safety profile with fever as the most frequent adverse event, observed in 54.7%, followed by extrapyramidal symptoms and hypopotassemia in 14.2% of treated patients. All detected adverse events were reversible. There was no evidence of cumulative hematologic toxicity. Conclusions: CIGB-128 demonstrated signs of

  1. A Biobehavioral Perspective on Depressive Symptoms in Patients with a Cerebral Astrocytoma (United States)

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


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

  2. Cerebral Pilocytic Astrocytoma with Spontaneous Intracranial Hemorrhage in Adults

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    Hao-Ming Li


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

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

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


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

  4. Bafetinib in Treating Patients With Recurrent High-Grade Glioma or Brain Metastases (United States)


    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

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

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    Mukherjee Purna


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

  6. High-grading and over-quota discarding in mixed fisheries

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    Batsleer, J.; Hamon, K.G.; Overzee, van H.M.J.; Rijnsdorp, A.D.; Poos, J.J.


    High-grading is the decision by fishers to discard fish of low value that allows them to land more valuable fish. A literature review showed high-grading is reported in commercial and non-commercial fisheries around the world, although the number of observations is small. High-grading occurs in


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


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

  8. High grade neuroendocrine neoplasm of the antrum and orbit. (United States)

    MacIntosh, Peter W; Jakobiec, Frederick A; Stagner, Anna M; Gilani, Sapideh; Fay, Aaron


    Neuroendocrine malignancies-tumors characterized by the production of dense-core secretory granules-are most often encountered in the lungs and can also be found in extrapulmonary sites. Our patient had a primary neuroendocrine tumor of the antrum with an elusive cell of origin that secondarily invaded the inferior orbit. In the sinuses, neuroendocrine tumors may be confused with infectious sinusitis or squamous cell carcinoma. There are no known pathognomonic clinical or radiographic signs to distinguish these tumors from other conditions. Diagnosis depends on a biopsy with histopathologic and immunohistochemical analysis to identify biomarkers such as synaptophysin, chromogranin, CD56 and neuron specific enolase. Our patient's tumor defied precise immunohistochemical characterization because of its primitive character and erratic biomarker expression. The diagnosis oscillated between a neuroendocrine carcinoma and an ectopic esthesioneuroblastoma grade IV-hence the use of the more generic nosologic category of neuroendocrine neoplasm without specifying a neuronal or epithelial origin. Data to guide management are limited, particularly in the ophthalmic literature, and derive from experience with tumors of the sinonasal compartments. In the present case of a sino-orbital high grade neuroendocrine neoplasm, regional lymph node metastases developed shortly after presentation. The tumor has responded well to chemotherapy and radiation, but recurrence is often encountered within 2 years in this class of neoplasms. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. High-Grade Leiomyosarcoma Arising in a Previously Replanted Limb

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    Tiffany J. Pan


    Full Text Available Sarcoma development has been associated with genetics, irradiation, viral infections, and immunodeficiency. Reports of sarcomas arising in the setting of prior trauma, as in burn scars or fracture sites, are rare. We report a case of a leiomyosarcoma arising in an arm that had previously been replanted at the level of the elbow joint following traumatic amputation when the patient was eight years old. He presented twenty-four years later with a 10.8 cm mass in the replanted arm located on the volar forearm. The tumor was completely resected and pathology examination showed a high-grade, subfascial spindle cell sarcoma diagnosed as a grade 3 leiomyosarcoma with stage pT2bNxMx. The patient underwent treatment with brachytherapy, reconstruction with a free flap, and subsequently chemotherapy. To the best of our knowledge, this is the first case report of leiomyosarcoma developing in a replanted extremity. Development of leiomyosarcoma in this case could be related to revascularization, scar formation, or chronic injury after replantation. The patient remains healthy without signs of recurrence at three-year follow-up.

  10. Yoga May Mitigate Decreases in High School Grades

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    Bethany Butzer


    Full Text Available This study involves an exploratory examination of the effects of a 12-week school-based yoga intervention on changes in grade point average (GPA in 9th and 10th grade students. Participants included 95 high school students who had registered for physical education (PE in spring 2010. PE class sections were group randomized to receive either a yoga intervention or a PE-as-usual control condition. The yoga intervention took place during the entire third quarter and half of the fourth quarter of the school year, and quarterly GPA was collected via school records at the end of the school year. Results revealed a significant interaction between group and quarter suggesting that GPA differed between the yoga and control groups over time. Post hoc tests revealed that while both groups exhibited a general decline in GPA over the school year, the control group exhibited a significantly greater decline in GPA from quarter 1 to quarter 3 than the yoga group. Both groups showed equivalent declines in GPA in quarter 4 after the yoga intervention had ended. The results suggest that yoga may have a protective effect on academic performance by preventing declines in GPA; however these preventive effects may not persist once yoga practice is discontinued.

  11. Expression of CD133 as a putative prognostic biomarker to predict intracranial dissemination of primary spinal cord astrocytoma. (United States)

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


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

  12. Phase 2 Study of Temozolomide-Based Chemoradiation Therapy for High-Risk Low-Grade Gliomas: Preliminary Results of Radiation Therapy Oncology Group 0424

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    Fisher, Barbara J., E-mail: [London Regional Cancer Program, London, Ontario (Canada); Hu, Chen [Radiation Therapy Oncology Group-Statistical Center, Philadelphia, Pennsylvania (United States); Macdonald, David R. [London Regional Cancer Program, London, Ontario (Canada); Lesser, Glenn J. [Wake Forest University Baptist Medical Center, Winston-Salem, North Carolina (United States); Coons, Stephen W. [Barrow Neurological Institute, Phoenix, Arizona (United States); Brachman, David G. [Arizona Oncology Services Foundation, Phoenix, Arizona (United States); Ryu, Samuel [Henry Ford Hospital, Detroit, Michigan (United States); Werner-Wasik, Maria [Thomas Jefferson University Hospital Center, Philadelphia, Pennsylvania (United States); Bahary, Jean-Paul [Centre Hospitalier de l' Université de Montréal-Notre Dame, Montreal, Quebec (Canada); Liu, Junfeng [GCE Solutions, Inc., Bloomington, Illinois (United States); Chakravarti, Arnab [The Ohio State University, The James, Columbus, Ohio (United States); Mehta, Minesh [University of Maryland Medical Systems, Baltimore, Maryland (United States)


    Purpose: Radiation Therapy Oncology Group (RTOG) 0424 was a phase 2 study of a high-risk low-grade glioma (LGG) population who were treated with temozolomide (TMZ) and radiation therapy (RT), and outcomes were compared to those of historical controls. This study was designed to detect a 43% increase in median survival time (MST) from 40.5 to 57.9 months and a 20% improvement in 3-year overall survival (OS) rate from 54% to 65% at a 10% significance level (1-sided) and 96% power. Methods and Materials: Patients with LGGs with 3 or more risk factors for recurrence (age ≥40 years, astrocytoma histology, bihemispherical tumor, preoperative tumor diameter of ≥6 cm, or a preoperative neurological function status of >1) were treated with RT (54 Gy in 30 fractions) and concurrent and adjuvant TMZ. Results: From 2005 to 2009, 129 evaluable patients (75 males and 54 females) were accrued. Median age was 49 years; 91% had a Zubrod score of 0 or 1; and 69%, 25%, and 6% of patients had 3, 4, and 5 risk factors, respectively. Patients had median and minimum follow-up examinations of 4.1 years and 3 years, respectively. The 3-year OS rate was 73.1% (95% confidence interval: 65.3%-80.8%), which was significantly improved compared to that of prespecified historical control values (P<.001). Median survival time has not yet been reached. Three-year progression-free survival was 59.2%. Grades 3 and 4 adverse events occurred in 43% and 10% of patients, respectively. One patient died of herpes encephalitis. Conclusions: The 3-year OS rate of 73.1% for RTOG 0424 high-risk LGG patients is higher than that reported for historical controls (P<.001) and the study-hypothesized rate of 65%.

  13. Spontaneous intratumoural and intraventricular haemorrhage associated with a pilomyxoid astrocytoma in the hypothalamic/chiasmatic region. (United States)

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


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

  14. Multimodal target point assessment for stereotactic biopsy in children with diffuse bithalamic astrocytomas. (United States)

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


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

  15. Flow cytometric analysis of cellular DNA content in human astrocytomas and oligodendrogliomas. (United States)

    Ahyai, A


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

  16. High Grade Infective Spondylolisthesis of Cervical Spine Secondary to Tuberculosis. (United States)

    Hadgaonkar, Shailesh; Shah, Kunal; Shyam, Ashok; Sancheti, Parag


    Spondylolisthesis coexisting with tuberculosis is rarely reported. There is a controversy whether spondylolisthesis coexists or precedes tuberculosis. Few cases of pathological spondylolisthesis secondary to tuberculous spondylodiscitis have been reported in the lumbar and lumbosacral spine. All cases in the literature presented as anterolisthesis, except one which presented as posterolisthesis of lumbar spine. Spondylolisthesis in the cervical spine is mainly degenerative and traumatic. Spondylolisthesis due to tuberculosis is not reported in the lower cervical spine. The exact mechanism of such an occurrence of spondylolisthesis with tuberculosis is sparsely reported in the literature and inadequately understood. We report a rare case of high grade pathological posterolisthesis of the lower cervical spine due to tubercular spondylodiscitis in a 67-year-old woman managed surgically with a three-year follow-up period. This case highlights the varied and complex presentation of tuberculosis of the lower cervical spine and gives insight into its pathogenesis, diagnosis, and management.

  17. Discrimination between Glioma Grades II and III Using Dynamic Susceptibility Perfusion MRI: A Meta-Analysis. (United States)

    Delgado, Anna F; Delgado, Alberto F


    DSC perfusion has been evaluated in the discrimination between low-grade and high-grade glioma but the diagnostic potential to discriminate beween glioma grades II and III remains unclear. Our aim was to evaluate the diagnostic accuracy of relative maximal CBV from DSC perfusion MR imaging to discriminate glioma grades II and III. A systematic literature search was performed in PubMed/MEDLINE, Embase, Web of Science, and Eligible studies reported on patients evaluated with relative maximal CBV derived from DSC with a confirmed neuropathologic diagnosis of glioma World Health Organization grades II and III. Studies reporting on mean or individual patient data were considered for inclusion. Data were analyzed by using inverse variance with the random-effects model and receiver operating characteristic curves describing optimal cutoffs and areas under the curve. Bivariate diagnostic random-effects meta-analysis was used to calculate diagnostic accuracy. Twenty-eight studies evaluating 727 individuals were included in the meta-analysis. Individual data were available from 10 studies comprising 190 individuals. The mean difference of relative maximal CBV between glioma grades II and III (n = 727) was 1.76 (95% CI, 1.27-2.24; P grades II and III at an optimal cutoff of 2.02. When we analyzed astrocytomas separately, the area under the curve increased to 0.86 but decreased to 0.61 when we analyzed oligodendrogliomas. A substantial heterogeneity was found among included studies. Glioma grade III had higher relative maximal CBV compared with glioma grade II. A high diagnostic accuracy was found for all patients and astrocytomas; however, the diagnostic accuracy was substantially reduced when discriminating oligodendroglioma grades II and III. © 2017 by American Journal of Neuroradiology.

  18. Induction of cellular proliferation in a human astrocytoma cell line by a Trypanosoma cruzi-derived antigen: a mechanism of pathogenesis? (United States)

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


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

  19. Alkali control of high-grade metamorphism and granitization

    Directory of Open Access Journals (Sweden)

    Oleg G. Safonov


    Full Text Available We review petrologic observations of reaction textures from high-grade rocks that suggest the passage of fluids with variable alkali activities. Development of these reaction textures is accompanied by regular compositional variations in plagioclase, pyroxenes, biotite, amphibole and garnet. The textures are interpreted in terms of exchange and net-transfer reactions controlled by the K and Na activities in the fluids. On the regional scale, these reactions operate in granitized, charnockitized, syenitized etc. shear zones within high-grade complexes. Thermodynamic calculations in simple chemical systems show that changes in mineral assemblages, including the transition from the hydrous to the anhydrous ones, may occur at constant pressure and temperature due only to variations in the H2O and the alkali activities. A simple procedure for estimating the activity of the two major alkali oxides, K2O and Na2O, is implemented in the TWQ software. Examples of calculations are presented for well-documented dehydration zones from South Africa, southern India, and Sri Lanka. The calculations have revealed two end-member regimes of alkalis during specific metamorphic processes: rock buffered, which is characteristic for the precursor rocks containing two feldspars, and fluid-buffered for the precursor rocks without K-feldspar. The observed reaction textures and the results of thermodynamic modeling are compared with the results of available experimental studies on the interaction of the alkali chloride and carbonate-bearing fluids with metamorphic rocks at mid-crustal conditions. The experiments show the complex effect of alkali activities in the fluid phase on the mineral assemblages. Both thermodynamic calculations and experiments closely reproduce paragenetic relations theoretically predicted by D.S. Korzhinskii in the 1940s.

  20. Leaks in nuclear grade high efficiency aerosol filters

    Energy Technology Data Exchange (ETDEWEB)

    Scripsick, Ronald Clyde [Univ. of California, Davis, CA (United States)


    Nuclear grade high efficiency aerosol filters, also known as high efficiency particulate air (HEPA) filters, are commonly used in air cleaning systems for removal of hazardous aerosols. Performance of the filter units is important in assuring health and environmental protection. The filter units are constructed from pleated packs of fiberglass filter media sealed into rigid frames. Results of previous studies on such filter units indicate that their performance may not be completely predicted by ideal performance of the fibrous filter media. In this study, departure from ideal performance is linked to leaks existing in filter units and overall filter unit performance is derived from independent performance of the individual filter unit components. The performance of 14 nuclear grade HEPA filter units (size 1, 25 cfm) with plywood frames was evaluated with a test system that permitted independent determination of penetration as a function of particle size for the whole filter unit, the filter unit frame, and the filter media pack. Tests were performed using a polydisperse aerosol of di-2-ethylhexyl phthalate with a count median diameter of 0.2 {mu}m and geometric standard deviation of 1.6. Flow rate and differential pressure were controlled from 1% to 100% of design values. Particle counts were made upstream and downstream of the filter unit with an optical particle counter (OPC). The OPC provided count information in 28 size channels over the particle diameter range from 0.1 to 0.7 μm. Results provide evidence for a two component leak model of filler unit performance with: (1) external leaks through filter unit frames, and (2) internal leaks through defects in the media and through the seal between the media pack and frame. For the filter units evaluated, these leaks dominate overall filter unit performance over much of the flow rate and particle size ranges tested.

  1. High-grade renal injuries are often isolated in sports-related trauma


    Patel, DP; Redshaw, JD; Breyer, BN; Smith, TG; Erickson, BA; Majercik, SD; Gaither, TW; Craig, JR; Gardner, S.; Presson, AP; Zhang, C.; Hotaling, JM; Brant, WO; Myers, JB


    © 2015 Elsevier Ltd. All rights reserved. Introduction: Most high-grade renal injuries (American Association for Surgery of Trauma (AAST) grades III-V) result from motor vehicle collisions associated with numerous concomitant injuries. Sports-related blunt renal injury tends to have a different mechanism, a solitary blow to the flank. We hypothesized that high-grade renal injury is often isolated in sports-related renal trauma. Material and methods: We identified patients with AAST grades III...

  2. Long-Term Sequelae after Cerebellar Astrocytoma Surgery

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap


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

  3. High bone sialoprotein (BSP expression correlates with increased tumor grade and predicts a poorer prognosis of high-grade glioma patients.

    Directory of Open Access Journals (Sweden)

    Tao Xu

    Full Text Available OBJECTIVES: To investigate the expression and prognostic value of bone sialoprotein (BSP in glioma patients. METHODS: We determined the expression of BSP using real-time RT-PCR and immunohistochemistry in tissue microarrays containing 15 normal brain and 270 glioma samples. Cumulative survival was calculated by the Kaplan-Meier method and analyzed by the log-rank test. Univariate and multivariate analyses were performed by the stepwise forward Cox regression model. RESULTS: Both BSP mRNA and protein levels were significantly elevated in high-grade glioma tissues compared with those of normal brain and low-grade glioma tissues, and BSP expression positively correlated with tumor grade (P<0.001. Univariate and multivariate analysis showed high BSP expression was an independent prognostic factor for a shorter progression-free survival (PFS and overall survival (OS in both grade III and grade IV glioma patients [hazard ratio (HR = 2.549 and 3.154 for grade III glioma, and HR = 1.637 and 1.574 for grade IV glioma, respectively]. Patients with low BSP expression had a significantly longer median OS and PFS than those with high BSP expression. Small extent of resection and lineage of astrocyte served as independent risk factors of both shorter PFS and OS in grade III glioma patients; GBM patients without O(6-methylguanine (O(6-meG DNA methyltransferase (MGMT methylation and Karnofsky performance score (KPS less than 70 points were related to poor prognosis. Lack of radiotherapy related to shorter OS but not affect PFS in both grade III and grade IV glioma patients. CONCLUSION: High BSP expression occurs in a significant subset of high-grade glioma patients and predicts a poorer outcome. The study identifies a potentially useful molecular marker for the categorization and targeted therapy of gliomas.

  4. Malignant astrocytoma in elderly patients: where do we stand? (United States)

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


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

  5. Circulating microRNAs as Biomarkers for Pediatric Astrocytomas. (United States)

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


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

  6. Imaging Features of Pilocytic Astrocytoma in Cerebral Ventricles. (United States)

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


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

  7. Stroke and stroke mimics: a case of high grade glioma

    Directory of Open Access Journals (Sweden)

    Roberta Wolffenbüttel Argenti


    Full Text Available The clinical diagnosis of acute stroke is inaccurate approximately 10%-30% of the time, which can lead to unnecessary administration of thrombolytic therapy or delays in appropriate therapy. Rapid and accurate neuroimaging triage is essential to guide therapy and exclude mimics. Although many conditions that mimic stroke clinically have imaging appearances that can overlap acute stroke, these conditions can be differentiated in most cases by using a careful pattern-based approach. We describe a case of 67 yo male patient who had a clinic of wakeup stroke and at the first magnetic resonance image (MRI it was found that was an acute stroke of middle cerebral artery.The patient did not improve and a second MRI  revelead a two times growth of the lesion, and the MRI findings were compatible with tumor. At the surgery they found a infiltrative lesion and the anatomopathological exam showed that it was a high grade glioma.The diagnosis of ischemic stroke is often straight forward; however, the clinical diagnosis of acute stroke is inaccurate in many cases. Furthermore, many of these conditions, such as encephalitis, mass lesions, seizures, hypoglycemia, transient global amnesia (TGA,demyelinating disease, drug toxicity, and metabolic disturbances, have imaging appearances that can mimic acute or subacute infarction; however, an accurate diagnosis can often be made by using a pattern-based approach.

  8. Concurrent thermochemoradiotherapy for brain high-grade glioma

    Energy Technology Data Exchange (ETDEWEB)

    Ryabova, A. I., E-mail:; Novikov, V. A.; Startseva, Zh. A.; Bober, E. E.; Frolova, I. G. [Tomsk Cancer Research Institute, Tomsk, 634050 (Russian Federation); Choinzonov, E. L. [Tomsk Cancer Research Institute, Tomsk, 634050 (Russian Federation); Siberian State Medical University, Tomsk, 634050 (Russian Federation); Gribova, O. V. [Tomsk Cancer Research Institute, Tomsk, 634050 (Russian Federation); National Research Tomsk Polytechnic University, Tomsk, 634050 (Russian Federation); Baranova, A. V. [National Research Tomsk Polytechnic University, Tomsk, 634050 (Russian Federation)


    Despite the achievements in the current strategies for treatment, the prognosis in malignant glioma patients remains unsatisfactory. Hyperthermia is currently considered to be the most effective and universal modifier of radiotherapy and chemotherapy. Preliminary treatment outcomes for 28 patients with newly diagnosed (23) and recurrent (5) high-grade gliomas were presented. All the patients received multimodality treatment including surgery, thermoche-moradiotherapy followed by 4 cycles of adjuvant chemotherapy. All the patients endured thermochemoradiotherapy well. A complication, limited skin burn (II stage), was diagnosed in two cases and treated conservatively without treatment interruption. A month after thermochemoradiotherapy the results were as follows: complete regression was achieved in 4 cases, partial regression in 4 cases, stable disease in 14 cases and disease progression in 6 cases (one of them is pseudo-progression). After completing the adjuvant chemotherapy 2 more patients demonstrated complete response and 1 patient had disease progression. Introduction of local hyperthermia in multimodal therapy of malignant glioma does not impair the combined modality treatment tolerability of patients with malignant gliomas. A small number of studied patients and short follow-up time do not allow making reliable conclusions about the impact of local hyperthermia on the treatment outcomes; however, there is a tendency towards the increase in disease-free survival in the patients with newly diagnosed malignant gliomas.

  9. High-Performance Slab-on-Grade Foundation Insulation Retrofits

    Energy Technology Data Exchange (ETDEWEB)

    Goldberg, Louise F. [NorthernSTAR, St. Paul, MN (United States); Mosiman, Garrett E. [NorthernSTAR, St. Paul, MN (United States)


    A more accurate assessment of slab-on-grade foundation insulation energy savings than traditionally possible is now feasible. This has been enabled by advances in whole building energy simulation with 3-dimensional foundation modelling integration at each time step together with an experimental measurement of the site energy savings of SOG foundation insulation. Ten SOG insulation strategies were evaluated on a test building to identify an optimum retrofit insulation strategy in a zone 6 climate (Minneapolis, MN). The optimum insulation strategy in terms of energy savings and cost effectiveness consisted of two components: (a) R-20 XPS insulation above grade, and, (b) R-20 insulation at grade (comprising an outer layer of R-10 insulation and an interior layer of R-12 poured polyurethane insulation) tapering to R-10 XPS insulation at half the below-grade wall height (the lower half of the stem wall was uninsulated).

  10. Body mass index, serum total cholesterol, and risk of gastric high-grade dysplasia


    Huang, Ya-Kai; Kang, Wei-Ming; Ma, Zhi-Qiang; Liu, Yu-Qin; Zhou, Li; Yu, Jian-Chun


    Abstract Obesity is related to an increased risk of gastric cardia cancer. However, the influences of excess body weight and serum total cholesterol on the risk of gastric high-grade dysplasia have not been fully characterized. A case?control study was conducted to explore the relationships between body mass index (BMI), serum total cholesterol level, and the risk of gastric high-grade dysplasia in Chinese adults. A total of 893 consecutive patients with gastric high-grade dysplasia (537 men ...

  11. Primary balloon angioplasty for symptomatic, high-grade intracranial stenosis. (United States)

    Tomycz, Luke; Bansal, Neil K; Lockney, Tim; Strothers, Megan; Connors, John J; Shay, Scott; Singer, Robert J


    In light of recent controversy about the safety and efficacy of intracranial stenting, we sought to evaluate our experience with primary balloon angioplasty for symptomatic, high-grade intracranial stenosis. All intracranial angioplasty cases performed at Vanderbilt University Medical Center from 2006 to 2011 were retrospectively reviewed for degree of stenosis pre- and post-procedure. Immediate peri-procedural complications were evaluated as well as one-month and long-term outcomes. A total of 26 patients were included in the study with a mean age of 63.0 years and a mean follow-up of 350.2 days. The average pre-procedure stenosis was 71.2%. The immediate, average post-procedure stenosis was 46.6%, and the average post-procedure stenosis at last angiographic follow-up was 44.5%. Retreatment was required in only 3.8% of patients. The primary end-point of major stroke or death at 30 days was observed in 11.5%, and the overall intra-procedural complication rate was 7.7%. The incidence of stroke or death at last follow-up was 15.4%, which is comparable to the one-year stroke or death rate in the medical arm of the SAMPRISS trial. In this retrospective series, primary balloon angioplasty was found to be effective as a treatment option for symptomatic intracranial stenosis with the risk of stroke or death at 30 days higher than the medical arm of SAMPRIS but lower than the stenting arm. The one-year risk of stroke was comparable to that reported for the one-year outcomes in the SAMPRISS medical arm.

  12. Preserved splenic function after angioembolisation of high grade injury. (United States)

    Skattum, Jorunn; Titze, Thomas Larsen; Dormagen, Johann Baptist; Aaberge, Ingeborg S; Bechensteen, Anne Grete; Gaarder, Per Ivar; Gaarder, Christine; Heier, Hans Erik; Næss, Pål Aksel


    After introducing splenic artery embolisation (SAE) in the institutional treatment protocol for splenic injury, we wanted to evaluate the effects of SAE on splenic function and assess the need for immunisation in SAE treated patients. 15 SAE patients and 14 splenectomised (SPL) patients were included and 29 healthy blood donors volunteered as controls. Clinical examination, medical history, general blood counts, immunoglobulin quantifications and flowcytometric analysis of lymphocyte phenotypes were performed. Peripheral blood smears from all patients and controls were examined for Howell-Jolly (H-J) bodies. Abdominal doppler, gray scale and contrast enhanced ultrasound (CEUS) were performed on all the SAE patients. Leukocyte and platelet counts were elevated in both SAE and SPL individuals compared to controls. The proportion of memory B-lymphocytes did not differ significantly from controls in either group. In the SAE group total IgA, IgM and IgG levels as well as pneumococcal serotype specific IgG and IgM antibody levels did not differ from the control group. In the SPL group total IgA and IgG Pneumovax(®) (PPV23) antibody levels were significantly increased, and 5 of 12 pneumococcal serotype specific IgGs and IgMs were significantly elevated. H-J bodies were only detected in the SPL group. CEUS confirmed normal sized and well perfused spleens in all SAE patients. In our study non-operative management (NOM) of high grade splenic injuries including SAE, was followed by an increase in total leukocyte and platelet counts. Normal levels of immunoglobulins and memory B cells, absence of H-J bodies and preserved splenic size and intraparenchymal blood flow suggest that SAE has only minor impact on splenic function and that immunisation probably is unnecessary. Copyright © 2010 Elsevier Ltd. All rights reserved.

  13. Surgical treatment of esophageal high-grade dysplasia. (United States)

    Reed, Michael F; Tolis, George; Edil, Barish H; Allan, James S; Donahue, Dean M; Gaissert, Henning A; Moncure, Ashby C; Wain, John C; Wright, Cameron D; Mathisen, Douglas J


    Barrett's esophagus, high-grade dysplasia (HGD), and invasive cancer are steps in the progression of esophageal adenocarcinoma. While surgery is recommended for resectable invasive adenocarcinoma, a number of treatment modalities are advocated for HGD. The purpose of this study is to determine the outcomes after surgery for HGD. We identified cases of HGD based on endoscopic biopsy in a single institution's databases from 1980 through 2001. Records were reviewed for patient characteristics, treatments, staging, and outcomes. In a 22-year period, 869 cases of esophageal adenocarcinoma and 1,614 cases of Barrett's esophagus were diagnosed. Of these, 115 had HGD without pretreatment evidence of invasion. Forty-nine patients with HGD underwent resection (mean age, 59 years) as initial treatment. Forty-seven had endoscopic treatment (mean age, 70 years) by photodynamic therapy or endoscopic mucosal resection. Seven of the endoscopically treated patients failed, with three undergoing surgery and four observation. Nineteen patients were initially observed, with six eventually having surgery. For the 49 initially treated surgically, one (2%) operative mortality occurred. Invasive adenocarcinoma was present in 18 (37%). The five-year survival was 83% for all resected HGD patients (91% for those without invasion, 68% with invasion). Three of the eight deaths in those with invasion were from recurrent adenocarcinoma. Surgical resection of esophageal HGD can be performed with low mortality and allows long-term survival. A significant percentage with an initial diagnosis of HGD will have invasive disease at resection. Surgery is the optimal treatment for HGD unless contraindicated by severe comorbidities.

  14. Non-operative management attempted for selective high grade blunt hepatosplenic trauma is a feasible strategy


    Hsieh, Ting-Min; Cheng Tsai, Tsung; Liang, Jiun-Lung; Che Lin, Chih


    Background There is growing evidence of clinical data recently for successful outcomes of non-operative management (NOM) for blunt hepatic and spleen injuries (BHSI). However, the effectiveness of NOM for high-grade BHSI remains undefined. The aim of the present study was to review our experience with NOM in high-grade BHSI and compare results with the existing related data worldwide. Methods In this retrospectively protocol-driven study, 150 patients with grade 3–5 BHSI were enrolled during ...

  15. Functionally graded materials produced with high power lasers

    NARCIS (Netherlands)

    de Hosson, J.T.M.; Pei, Y.T.; Kumar, A; Chung, YW; Moore, JJ; Doll, GL; Yatsui, K; Misra, DS


    With a well-controlled laser melt injection (LMI) process, for the first time the feasibility is demonstrated to produce SiC particles (SiCp) reinforced Ti6Al4V functionally graded materials (FGMs). SiCp are injected just behind the laser beam into the extended part of the laser melt pool that is

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

  17. Prognostic value of metabolic tumor volume on {sup 11}C-methionine PET in predicting progression-free survival in high-grade glioma

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Min Young; Paeng, Jin Chul; Cheon, Gi Jeong; Lee, Dong Soo; Chung, June Key; Kang, Keon Wook [Dept. of Nuclear Medicine, Seoul National University Hospital, Seoul (Korea, Republic of); Kim, E. Edmund [Dept. of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul (Korea, Republic of)


    C-11 methionine (MET) PET is commonly used for diagnosing high-grade glioma (HGG). Recently, volumetric analysis has been widely applied to oncologic PET imaging. In this study, we investigated the prognostic value of metabolic tumor volume (MTV) on MET PET in HGG. A total of 30 patients with anaplastic astrocytoma (n = 12) and glioblastoma multiforme (n = 18) who underwent MET PET before treatment (surgery followed by chemo-radiotherapy) were retrospectively enrolled. Maximal tumor-to-normal brain ratio (TNR{sub max}, maximum tumor activity divided by mean of normal tissue) and MTV (volume of tumor tissue that shows uptake >1.3-fold of mean uptake in normal tissue) were measured on MET PET. Adult patients were classified into two subgroups according to Radiation Therapy Oncology Group Recursive Partitioning Analysis (RTOG RPA) classification. Prognostic values of TNR{sub max}, MTV and clinicopathologic factors were evaluated with regard to progression-free survival (PFS). Median PFS of all patients was 7.9 months (range 1.0–53.8 months). In univariate analysis, MTV (cutoff 35 cm{sup 3}) was a significant prognostic factor for PFS (P = 0.01), whereas TNR{sub max} (cutoff 3.3) and RTOG RPA class were not (P = 0.80 and 0.61, respectively). Treatment of surgical resection exhibited a borderline significance (P = 0.06). In multivariate analysis, MTV was the only independent prognostic factor for PFS (P = 0.03). MTV on MET PET is a significant and independent prognostic factor for PFS in HGG patients, whereas TNR{sub max} is not. Thus, performing volumetric analysis of MET PET is recommended in HGG for better prognostication.

  18. Extent of high-grade prostatic intraepithelial neoplasia is not a ...

    African Journals Online (AJOL)

    Objective: High-grade prostatic intraepithelial neoplasia (PIN) is a well accepted pre-cursor of invasive prostate cancer. Most investigators agree that a diagnosis of high-grade PIN warrants repeat transrectal ultrasound guided biopsy. We set out to investigate risk factors for cancer among a modern cohort of men with ...

  19. Natural history of high-grade cervical intraepithelial neoplasia : a review of prognostic biomarkers

    NARCIS (Netherlands)

    Koeneman, Margot M.; Kruitwagen, Roy F. P. M.; Nijman, Hans W.; Slangen, Brigitte F. M.; Van Gorp, Toon; Kruse, Arnold-Jan

    The natural history of high-grade cervical intraepithelial neoplasia (CIN) is largely unpredictable and current histopathological examination is unable to differentiate between lesions that will regress and those that will not. Therefore, most high-grade lesions are currently treated by surgical

  20. Pilocytic Astrocytoma of Fornix Mimicking a Colloid Cyst: Report of 2 Cases and Review of the Literature. (United States)

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


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

  1. The effect of IDH1 mutation on the structural connectome in malignant astrocytoma. (United States)

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


    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.

  2. High Performance Slab-on-Grade Foundation Insulation Retrofits

    Energy Technology Data Exchange (ETDEWEB)

    Goldberg, Louise F. [NorthernSTAR, St. Paul, MN (United States); Mosiman, Garrett E. [NorthernSTAR, St. Paul, MN (United States)


    ?A more accurate assessment of SOG foundation insulation energy savings than traditionally possible is now feasible. This has been enabled by advances in whole building energy simulation with 3-dimensional foundation modelling integration at each time step together with an experimental measurement of the site energy savings of SOG foundation insulation. Ten SOG insulation strategies were evaluated on a test building to identify an optimum retrofit insulation strategy in a zone 6 climate (Minneapolis, MN). The optimum insulation strategy in terms of energy savings and cost effectiveness consisted of two components: (a) R-20 XPS insulation above grade, and, (b) R-20 insulation at grade (comprising an outer layer of R-10 insulation and an interior layer of R-12 poured polyurethane insulation) tapering to R-10 XPS insulation at half the below-grade wall height (the lower half of the stem wall was uninsulated). The optimum insulation strategy was applied to single and multi-family residential buildings in climate zone 4 - 7. The highest site energy savings of 5% was realized for a single family home in Duluth, MN, and the lowest savings of 1.4 % for a 4-unit townhouse in Richmond, VA. SOG foundation insulation retrofit simple paybacks ranged from 18 to 47 years. There are other benefits of SOG foundation insulation resulting from the increase in the slab surface temperatures. These include increased occupant thermal comfort, and a decrease in slab surface condensation particularly around the slab perimeter.

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

    African Journals Online (AJOL)

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

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

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


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

  5. The differential diagnosis of pilocytic astrocytoma with atypical features and malignant glioma: an analysis of 16 cases with emphasis on distinguishing molecular features. (United States)

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


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

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


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


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

  7. A Comparison of High School Student Interests across Three Grade and Ability Levels. (United States)

    Gill, Newell T.


    Students (Grades 9-11) in two Florida metropolitan high schools rated their interest in 28 topics, such as travel, popular music, religion, the opposite sex, war, and politics. Interests were analyzed by sex, grade, and ability track in English (Honors, Average, Basic). Findings, especially those on romantic interests, are discussed. (SJL)

  8. A graded d-spacing multilayer telescope for high-energy x-ray astronomy

    DEFF Research Database (Denmark)

    Christensen, Finn Erland; Hornstrup, Allan; WESTERGAARD, NJ


    A high energy telescope design is presented which combines grazing incidence geometry with Bragg reflection in a graded d-spacing multilayer coating to obtain significant sensitivity up to --6O keV. The concept utilizes total reflection and first order Bragg reflection in a graded d-spacing multi...

  9. Number Grades: The Non Sequitur in Junior High School Art Education (United States)

    Lewis, Joan B.


    Art must be appreciated by the student as a subject which allows for freedom of self-expression and which provides an opportunity for self-awareness and self-evaluation. Examines the value of number grades for evaluating progress in art by junior high school students and discusses some alternatives to number grades. (Author/RK)

  10. Exploring High-Achieving Sixth Grade Students' Erroneous Answers and Misconceptions on the Angle Concept (United States)

    Bütüner, Suphi Önder; Filiz, Mehmet


    The aim of this research was to investigate high achievers' erroneous answers and misconceptions on the angle concept. The participants consisted of 233 grade 6 students drawn from eight classes in two well-established elementary schools of Trabzon, Turkey. All the participants were considered to be current achievers in mathematics, graded 4 or 5…

  11. Radiological and clinical outcome of non surgical management for pediatric high grade spondylolisthesis. (United States)

    Bourassa-Moreau, Etienne; Labelle, Hubert; Mac-Thiong, Jean-Marc


    To describe and compare the quality of life of patients with pediatric high-grade spondylolisthesis managed non-operatively and operatively. Some authors consider pediatric high-grade spondylolisthesis as an absolute indication for surgery, regardless of symptoms while others sometimes recommend observation in asymptomatic patients. Very little is known about the indications and outcome of non-operatively managed high-grade spondylolisthesis. A prospective database comprising all the spondylolisthesis cases from a single pediatric institution was reviewed in order to identify all cases of high grade spondylolisthesis. Quality of life data from Short form (SF)-12 and Scoliosis Research Society (SRS)-22 questionnaires were collected. Non-operatively treated patients were identified and compared to surgically treated patients at baseline and at last follow-up. 34 spondylolisthesis were identified as high grade and 5 of them were non-operatively treated. Quality of life questionnaires showed less impairment in the non-operative group when compared to the surgical group preoperatively. Moreover at last follow-up, quality of life questionnaires were similar between the two groups. There was no worsening of quality of life observed in non-operative patients during follow-up. The quality of life after surgical treatment of high grade spondylolisthesis is similar to that of patients with high grade spondylolisthesis and mild symptoms undergoing non-operative treatment.

  12. Association of Myelinated Retinal Nerve Fibers With Acquired Mulberry Retinal Astrocytoma: Coincidental or Relational? (United States)

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


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

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

    NARCIS (Netherlands)

    Dirven, Clemens Maria Franciscus


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

  14. Overdiagnosis of high-grade dysplasia in Barrett's esophagus: a multicenter, international study. (United States)

    Sangle, Nikhil A; Taylor, Shari L; Emond, Mary J; Depot, Michelle; Overholt, Bergein F; Bronner, Mary P


    Numerous histological mimics of high-grade dysplasia in Barrett's esophagus predispose to overdiagnosis and potential serious mismanagement, including unnecessary esophagectomy. This study investigates the prevalence and sources of this problem. Biopsies from 485 patients diagnosed with Barrett's high-grade dysplasia were screened for a multi-institutional, international Barrett's endoscopic ablation trial. Screening included review of the original diagnostic slides and an additional protocol endoscopy with an extensive biopsy sampling. Observer variability by the study pathologists was assessed through two blinded diagnostic rounds on 437 biopsies from 26 random study endoscopies. Study diagnostic reassessments revealed significantly lower rates of high-grade dysplasia. Only 248 patients (51%) were confirmed to have high-grade dysplasia. The remaining patients had inflamed gastric cardia without Barrett's (n=18; 7%), Barrett's without dysplasia (n=35; 15%), indefinite change (n=61; 26%), low-grade dysplasia (n=79; 33%), adenocarcinoma (n=43; 18%), and other (n=1; overdiagnosis included Barrett's inflammatory atypia (n=182), atypia limited to the basal metaplastic glands (n=147), imprecise criteria for low grade neoplasia (n=102), tangential sectioning artifact (n=59), and reactive gastric cardiac mucosa (n=38). A total of 194 patients (40%) were overdiagnosed with Barrett's high-grade dysplasia, as affirmed by the extensive screening process and high-level study pathologist agreement. The multiple diagnostic pitfalls uncovered should help raise pathologists' awareness of this problem and improve diagnostic accuracy.

  15. A population-based study of high-grade gliomas and mutated isocitrate dehydrogenase 1

    DEFF Research Database (Denmark)

    Dahlrot, Rikke H; Kristensen, Bjarne W; Hjelmborg, Jacob


    High-grade gliomas have a dismal prognosis, and prognostic factors are needed to optimize treatment algorithms. In this study we identified clinical prognostic factors as well as the prognostic value of isocitrate dehydrogenase 1 (IDH1) status in a population-based group of patients with high......-grade gliomas. Using the Danish Cancer Registry and the Danish Pathology Databank we identified 359 patients: 234 had WHO grade IV gliomas, 58 had WHO grade III gliomas, and 67 were diagnosed clinically. Mutated IDH1 was predominantly observed in oligodendroglial tumors (WHO grade III). Patients with mutated...... IDH1 had a significantly better outcome than patients with wildtype IDH1: 2-year OS 59% and 18%, respectively (HR 0.38, 95% CI 0.21-0.68). However, when adjusting for other prognostic factors, IDH1 status was not a significant independent prognostic factor (HR=0.58, 95% CI 0.32-1.07). Young age...

  16. Salivary gland hybrid tumour revisited: could they represent high-grade transformation in a low-grade neoplasm? (United States)

    Hellquist, Henrik; Skalova, Alena; Azadeh, Bahram


    Salivary gland hybrid tumour, first described in 1996, is a very rare neoplasm for which exact morphological criteria have not been universally agreed upon. In contrast, the concept of high-grade transformation (HGT) in salivary neoplasms has been widely accepted during the last decade, and the number of reported cases is rapidly increasing. A review of the literature revealed 38 cases of hybrid tumour reported in 22 publications. During approximately the same time period, well over 100 cases of HGT in salivary neoplasms have been reported. There are important histological similarities between hybrid tumours and salivary tumours with HGT. In the latter, containing one tumour component of low-grade malignancy and the other of high grade, the two tumour components are not entirely separated and appear to originate in the same area. Virtually, all cases reported as hybrid tumour had no clear lines of demarcation between the two tumour types. We are inclined to suggest that most of the 38 cases of hybrid tumours described in the literature would today better be called tumour with HGT rather than hybrid tumour. The relative proportion of the two components may vary, and the high-grade component is sometimes very small, which emphasises the importance of very generous sampling of the surgical specimen. The molecular genetic mechanisms responsible for HGT, including what used to be called hybrid tumour, remain largely unknown. Abnormalities of a few genes (including p53, C-MYC, cyclin D1, HER-2/neu) have been documented. As insufficient data exist on gene abnormalities in these lesions, conclusions as to whether or not they have a common origin and which mechanisms are involved in transformation cannot be drawn. Due to the small number of cases reported, many of which lack follow-up details; indicators of prognosis of hybrid tumours are not available, but their behaviour seems to be similar to that of tumours with HGT, i.e. an accelerated aggressive course. HGT of

  17. Obesity increases the risk for high-grade prostate cancer: results from the REDUCE study. (United States)

    Vidal, Adriana C; Howard, Lauren E; Moreira, Daniel M; Castro-Santamaria, Ramiro; Andriole, Gerald L; Freedland, Stephen J


    Studies suggest that obesity is associated with lower risk of prostate cancer but more aggressive cancers. As obesity lowers PSA levels, these observations may be influenced by detection bias. We examined the association between obesity and risk of low- and high-grade prostate cancer in REDUCE, in which biopsies were largely independent of PSA. The REDUCE study tested dutasteride for prostate cancer risk reduction in men with a PSA of 2.5 to 10.0 ng/mL and a negative biopsy. Study participants included 6,729 men who underwent at least one on-study biopsy. The association between baseline body mass index (BMI obese) and risk of high-grade (Gleason ≥7) or low-grade prostate cancer (Gleason cancer was examined using multinomial logistic regression. Overall, 1,739 men (27%) were normal weight, 3,384 (53%) overweight, and 1,304 (20%) were obese. Obesity was associated with lower risk of low-grade prostate cancer in both univariable (OR, 0.74; P = 0.001) and multivariable analyses (OR, 0.79; P = 0.01). In univariable analysis, obesity was not associated with high-grade prostate cancer (OR, 1.08; P = 0.50). However, in multivariable analysis, obesity was associated with increased risk of high-grade prostate cancer (OR, 1.28; P = 0.042). This analysis was not able to address how obesity may influence prostate cancer progression. Obesity is associated with decreased risk of low-grade and increased risk of high-grade prostate cancer. These data provide further support to the hypothesis that obesity is associated with aggressive prostate cancer. Obesity is linked with aggressive prostate cancer. Avoiding obesity may prevent the risk of developing high-grade prostate cancer. ©2014 American Association for Cancer Research.

  18. San Joaquin, California, High-Speed Rail Grade Crossing Data Acquisition Characteristics, Methodology, and Risk Assessment (United States)


    This report discusses data acquisition and analysis for grade crossing risk analysis at the proposed San Joaquin High-Speed Rail Corridor in San Joaquin, California, and documents the data acquisition and analysis methodologies used to collect and an...

  19. Zircon Ion Microprobe Dating of High-Grade Rocks in Sri Lanka

    National Research Council Canada - National Science Library

    A. Kröner; I. S. Williams; W. Compston; N. Baur; P. W. Vitanage; L. R. K. Perera


    The high-grade gneisses of Sri Lanka display spectacular in-situ granulitization phenomena similar to those observed in southern India and of current interest for evolutionary models of the lower continental crust...

  20. Surgical Versus Nonsurgical Treatment for High-Grade Spondylolisthesis in Children and Adolescents


    Xue, Xuhong; Wei, Xiaochun; Li, Li


    Abstract The optimal management of high-grade spondylolisthesis in children and adolescent is controversial. There is a paucity of literature regarding operatively or nonoperative management in this setting. To assessment of the current state of evidence regarding high-grade spondylolisthesis treatment with the goal of obtaining outcome comparisons in these patients managed either operatively or nonoperatively. We performed a systematic literature search up to November 2014, using Medline, Em...

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

    Directory of Open Access Journals (Sweden)

    WANG Yin


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

  2. Prostatectomy-based validation of combined urine and plasma test for predicting high grade prostate cancer

    DEFF Research Database (Denmark)

    Albitar, Maher; Ma, Wanlong; Lund, Lars


    BACKGROUND: Distinguishing between low- and high-grade prostate cancers (PCa) is important, but biopsy may underestimate the actual grade of cancer. We have previously shown that urine/plasma-based prostate-specific biomarkers can predict high grade PCa. Our objective was to determine the accuracy...... of a test using cell-free RNA levels of biomarkers in predicting prostatectomy results. METHODS: This multicenter community-based prospective study was conducted using urine/blood samples collected from 306 patients. All recruited patients were treatment-naïve, without metastases, and had been biopsied......, designated a Gleason Score (GS) based on biopsy, and assigned to prostatectomy prior to participation in the study. The primary outcome measure was the urine/plasma test accuracy in predicting high grade PCa on prostatectomy compared with biopsy findings. Sensitivity and specificity were calculated using...

  3. Laser interstitial thermal therapy for subependymal giant cell astrocytoma: technical case report. (United States)

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


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

  4. A Novel Syndrome of Generalized Lipodystrophy Associated With Pilocytic Astrocytoma. (United States)

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


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

  5. Gastric low-grade MALT lymphoma, high-grade MALT lymphoma and diffuse large B cell lymphoma show different frequencies of trisomy

    NARCIS (Netherlands)

    Hoeve, M A; Gisbertz, I A; Schouten, H C; Schuuring, E; Bot, F J; Hermans, J; Hopman, A; Kluin, P M; Arends, J E; van Krieken, J H


    Gastric MALT lymphoma is a distinct entity related to Helicobacter pylori gastritis. Some studies suggest a role for trisomy 3 in the genesis of these lymphomas, but they mainly focused on low-grade MALT lymphoma. Gastric MALT lymphoma, however, comprises a spectrum from low- to high-grade cases.

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

    Directory of Open Access Journals (Sweden)

    Kruger Mathew M


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

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

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


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

  8. Combined "Infiltrating Astrocytoma/Pleomorphic Xanthoastrocytoma" Harboring IDH1 R132H and BRAF V600E Mutations. (United States)

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


    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.

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

    Aiello, Katherine A; Alter, Orly


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

  10. Blood Magnesium, and the Interaction with Calcium, on the Risk of High-Grade Prostate Cancer (United States)

    Motley, Saundra S.; Smith, Joseph A.; Concepcion, Raoul; Barocas, Daniel; Byerly, Susan


    Background Ionized calcium (Ca) and magnesium (Mg) compete as essential messengers to regulate cell proliferation and inflammation. We hypothesized that inadequate Mg levels, perhaps relative to Ca levels (e.g. a high Ca/Mg ratio) are associated with greater prostate cancer risk. Study Design In this biomarker sub-study of the Nashville Men's Health Study (NMHS), we included 494 NMHS participants, consisting of 98 high-grade (Gleason≥7) and 100 low-grade cancer cases, 133 prostate intraepithelial neoplasia (PIN) cases, and 163 controls without cancer or PIN at biopsy. Linear and logistic regression were used to determine associations between blood Ca, Mg, and the Ca/Mg ratio across controls and case groups while adjusting for potential confounding factors. Results Serum Mg levels were significantly lower, while the Ca/Mg ratio was significantly higher, among high-grade cases vs. controls (p = 0.04, p = 0.01, respectively). Elevated Mg was significantly associated with a lower risk of high-grade prostate cancer (OR = 0.26 (0.09, 0.85)). An elevated Ca/Mg ratio was also associated with an increased risk of high-grade prostate cancer (OR = 2.81 (1.24, 6.36) adjusted for serum Ca and Mg). In contrast, blood Ca levels were not significantly associated with prostate cancer or PIN.Mg, Ca, or Ca/Mg levels were not associated with low-grade cancer, PIN, PSA levels, prostate volume, or BPH treatment. Conclusion Low blood Mg levels and a high Ca/Mg ratio were significantly associated with high-grade prostate cancer. These findings suggest Mg affects prostate cancer risk perhaps through interacting with Ca. PMID:21541018

  11. Allograft Arthrodesis of the Knee in High-grade Osteosarcoma

    Directory of Open Access Journals (Sweden)

    Teng-Le Huang


    Conclusion: Due to the high rate of complications in this study, we conclude that allograft arthrodesis should be left as a salvage or “back-up” reconstructive procedure after resection of osteosarcoma around the knee, unless there are special indications for this procedure. We found allograft fracture to be the most common complication.

  12. Field experimental observations of highly graded sediment plumes

    DEFF Research Database (Denmark)

    Hjelmager Jensen, Jacob; Saremi, Sina; Jimenez, Carlos


    , gravitating towards the seafloor, were filmed simultaneously by four divers situated at different depths in the water column, and facing the plume at different angles. The processes were captured using GoPro-Hero-series cameras. The high-quality underwater footage from near-surface, mid-depth and near...

  13. Human papillomavirus viral load in predicting high-grade CIN in women with cervical smears showing only atypical squamous cells or low-grade squamous intraepithelial lesion


    Santos,André Luis Ferreira; Derchain,Sophie Françoise Mauricette; Martins,Marcos Roberto; Sarian,Luís Otávio Zanatta; Martinez,Edson Zangiacome; Syrjänen,Kari Juhani


    CONTEXT: Human papillomavirus (HPV) viral load may have an important role in predicting high-grade cervical intraepithelial neoplasia (CIN) in women with cervical smears showing atypical squamous cells or LSIL. OBJECTIVE: To determine whether the assessment of the viral load of high-risk HPV DNA is useful in predicting the detection of high-grade cervical intraepithelial neoplasia (CIN2 and 3) in women referred because of cervical smears showing only atypical squamous cells or LSIL. TYPE OF S...

  14. Field experimental observations of highly graded sediment plumes. (United States)

    Jensen, Jacob Hjelmager; Saremi, Sina; Jimenez, Carlos; Hadjioannou, Louis


    A field experiment in the waters off the south-eastern coast of Cyprus was carried out to study near-field formation of sediment plumes from dumping. Different loads of sediment were poured into calm and limpid waters one at the time from just above the sea surface. The associated plumes, gravitating towards the seafloor, were filmed simultaneously by four divers situated at different depths in the water column, and facing the plume at different angles. The processes were captured using GoPro-Hero-series cameras. The high-quality underwater footage from near-surface, mid-depth and near-bed positions gives unique insight into the dynamics of the descending plume and near-field dispersion processes, and enables good understanding of flow and sediment transport processes involved from-release-to-deposition of the load in a non-scaled environment. The high resolution images and footages are available through the link provided herein. Observations support the development of a detailed multi-fractional sediment plume model. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Intravenous flat-detector computed tomography angiography for high-grade carotid stenosis. (United States)

    Jeon, Jin Sue; Sheen, Seung Hun; Kim, Heung Cheol


    The significant feature of intravenous flat-detector computed tomography (IV FDCT) angiography is its role in neurointerventional setting without patient transfer. However, few studies have addressed the accuracy of IV FDCT in estimating carotid stenosis and length. This study examined the reliability of IV FDCT in the diagnosis of high-grade carotid stenosis and stenosis length with digital subtraction angiography (DSA) as the reference. Intravenous flat-detector CT and DSA were conducted simultaneously for 33 patients with 42 stenosed carotid arteries who were suspected of having symptomatic high-grade stenosis by carotid duplex ultrasound, magnetic resonance angiography, or CT angiography. The degree of stenosis and length discrepancy between 2 tests were recorded by 2 readers. The intraobserver and interobserver agreements were excellent for measuring high-grade carotid stenosis (κ = 0.87 and 0.82). Intravenous flat-detector CT had a sensitivity of 96.3%, specificity of 93.3%, and negative predictive value of 93.3% for detecting high-grade stenosis (≥70%) compared with DSA. Bland-Altman plots demonstrated excellent correlation of the degree of stenosis IV FDCT with DSA. Length discrepancy (IV FDCT - DSA, in millimeters) did not differ significantly according to degree of stenosis (Spearman rank test; r = 0.18, P = 0.26). Intravenous flat-detector CT can be a feasible and time-saving test for evaluating high-grade carotid stenosis and stenosis length.

  16. Research and development of intelligent controller for high-grade sanitary ware (United States)

    Bao, Kongjun; Shen, Qingping


    With the social and economic development and people's living standards improve, more and more emphasis on modern society, people improve the quality of family life, the use of intelligent controller applications in high-grade sanitary ware physiotherapy students. Analysis of high-grade sanitary ware physiotherapy common functions pointed out in the production and use of the possible risks, proposed implementation of the system hardware and matching, given the system software implementation process. High-grade sanitary ware physiotherapy intelligent controller not only to achieve elegant and beautiful, simple, physical therapy, water power, deodorant, multi-function, intelligent control, to meet the consumers, the high-end sanitary ware market, strong demand, Accelerate the enterprise product Upgrade and improve the competitiveness of enterprises.

  17. Inhibition of autophagy by 3-methyladenine protects 1321N1 astrocytoma cells against pyocyanin- and 1-hydroxyphenazine-induced toxicity. (United States)

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


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

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

    Directory of Open Access Journals (Sweden)

    Michelle Sexton

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

  19. Leadership Strategies in Implementation of High-School Standards-Based Grading Systems (United States)

    Pritzl, Jerome


    This multi-site case study examined leadership strategies used during successful implementation of standards-based grading systems in three Wisconsin high schools. It found that leaders' reported commitment, patience, and persistence showed evidence of sustainable, high-functioning systems. It drew two main conclusions: first, school leaders need…

  20. Preliminary stop of the TOPical Imiquimod treatment of high-grade Cervical intraepithelial neoplasia (TOPIC) trial. (United States)

    Koeneman, M M; Kruse, A J; Kooreman, L F S; Zur Hausen, A; Hopman, A H N; Sep, S J S; Van Gorp, T; Slangen, B F M; van Beekhuizen, H J; van de Sande, A J M; Gerestein, C G; Nijman, H W; Kruitwagen, R F P M


    The "TOPical Imiquimod treatment of high-grade Cervical intraepithelial neoplasia" (TOPIC) trial was stopped preliminary, due to lagging inclusions. This study aimed to evaluate the treatment efficacy and clinical applicability of imiquimod 5% cream in high-grade cervical intraepithelial neoplasia (CIN). The lagging inclusions were mainly due to a strong patient preference for either of the two treatment modalities. This prompted us to initiate a new study on the same subject, with a non-randomized, open-label design: the 'TOPical Imiquimod treatment of high-grade Cervical intraepithelial neoplasia (TOPIC)-3' study. Original TOPIC-trial: Medical Ethics Committee approval number METC13231; Identifier: NCT02329171, 22 December 2014. TOPIC-3 study: Medical Ethics Committee approval number METC162025; Identifier: NCT02917746, 16 September 2016.

  1. Molecular Biology in Pediatric High-Grade Glioma: Impact on Prognosis and Treatment

    Directory of Open Access Journals (Sweden)

    Daniela Rizzo


    Full Text Available High-grade gliomas are the main cause of death in children with brain tumours. Despite recent advances in cancer therapy, their prognosis remains poor and the treatment is still challenging. To date, surgery followed by radiotherapy and temozolomide is the standard therapy. However, increasing knowledge of glioma biology is starting to impact drug development towards targeted therapies. The identification of agents directed against molecular targets aims at going beyond the traditional therapeutic approach in order to develop a personalized therapy and improve the outcome of pediatric high-grade gliomas. In this paper, we critically review the literature regarding the genetic abnormalities implicated in the pathogenesis of pediatric malignant gliomas and the current development of molecularly targeted therapies. In particular, we analyse the impact of molecular biology on the prognosis and treatment of pediatric high-grade glioma, comparing it to that of adult gliomas.

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

    NARCIS (Netherlands)

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


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

  3. Digital PCR quantification of SERPINA1 predicts prognosis in high-grade glioma. (United States)

    Ookawa, Satoshi; Wanibuchi, Masahiko; Kataoka-Sasaki, Yuko; Sasaki, Masanori; Oka, Shinichi; Ohtaki, Shunya; Noshiro, Shouhei; Komatsu, Katsuya; Akiyama, Yukinori; Mikami, Takeshi; Mikuni, Nobuhiro; Kocsis, Jeffery D; Honmou, Osamu


    SERPINA1 plays an anti-inflammatory role in protecting tissues from proteolytic mechanisms. SERPINA1 is positive in gliomas by immunohistochemical analysis; however, the role of SERPINA1 including the relationship with prognosis has been uncertain. In recent years, digital polymerase chain reaction (PCR) has provided ultra-sensitive assessment of mRNA expression from formalin fixed paraffin embedded (FFPE) tissues. In this study, we quantitatively determined the expression of SERPINA1 in high-grade gliomas (HGGs) using digital PCR and analyzed its relationship with prognosis. A total of 29 FFPE surgical samples from patients with HGGs (7 of World Health Organization [WHO] grade III and 22 of WHO grade IV), and human glioblastoma cell lines, U87 and U118, were used for analysis. A qualitative assessment using immunostaining and quantitative assessment using digital PCR were performed to assess the expression of SERPINA1. The expression of SERPINA1 was demonstrated in glioma tissues and GBM cell lines by immunostaining. Digital PCR analysis showed that SERPINA1 was expressed in 14.3% and 63.6% of the tissues from patients with grade III and grade IV HGG, respectively (p = 0.035). The median overall survival of 38.8 months in the low SERPINA1 expression group was longer than that of 15.3 months in the high expression group (p = 0.030). The frequency and the amount of SERPINA1 expression were higher in grade IV than in grade III HGGs. The high expression of SERPINA1 indicates a poor prognosis of HGGs. Copyright © 2018. Published by Elsevier Inc.

  4. Detection of high-grade atypia nuclei in breast cancer imaging (United States)

    Noël, Henri; Roux, Ludovic; Lu, Shijian; Boudier, Thomas


    Along with mitotic count, nuclear pleomorphism or nuclear atypia is an important criterion for the grading of breast cancer in histopathology. Though some works have been done in mitosis detection (ICPR 2012,1 MICCAI 2013,2 and ICPR 2014), not much work has been dedicated to automated nuclear atypia grading, especially the most difficult task of detection of grade 3 nuclei. We propose the use of Convolutional Neural Networks for the automated detection of cell nuclei, using images from the three grades of breast cancer for training. The images were obtained from ICPR contests. Additional manual annotation was performed to classify pixels into five classes: stroma, nuclei, lymphocytes, mitosis and fat. At total of 3,000 thumbnail images of 101 × 101 pixels were used for training. By dividing this training set in an 80/20 ratio we could obtain good training results (around 90%). We tested our CNN on images of the three grades which were not in the training set. High grades nuclei were correctly classified. We then thresholded the classification map and performed basic analysis to keep only rounded objects. Our results show that mostly all atypical nuclei were correctly detected.

  5. Genome-wide methylation profiling identifies hypermethylated biomarkers in high-grade cervical intraepithelial neoplasia. (United States)

    Lendvai, Ágnes; Johannes, Frank; Grimm, Christina; Eijsink, Jasper J H; Wardenaar, René; Volders, Haukeline H; Klip, Harry G; Hollema, Harry; Jansen, Ritsert C; Schuuring, Ed; Wisman, G Bea A; van der Zee, Ate G J


    Epigenetic modifications, such as aberrant DNA promoter methylation, are frequently observed in cervical cancer. Identification of hypermethylated regions allowing discrimination between normal cervical epithelium and high-grade cervical intraepithelial neoplasia (CIN2/3), or worse, may improve current cervical cancer population-based screening programs. In this study, the DNA methylome of high-grade CIN lesions was studied using genome-wide DNA methylation screening to identify potential biomarkers for early diagnosis of cervical neoplasia. Methylated DNA Immunoprecipitation (MeDIP) combined with DNA microarray was used to compare DNA methylation profiles of epithelial cells derived from high-grade CIN lesions with normal cervical epithelium. Hypermethylated differentially methylated regions (DMRs) were identified. Validation of nine selected DMRs using BSP and MSP in cervical tissue revealed methylation in 63.2-94.7% high-grade CIN and in 59.3-100% cervical carcinomas. QMSP for the two most significant high-grade CIN-specific methylation markers was conducted exploring test performance in a large series of cervical scrapings. Frequency and relative level of methylation were significantly different between normal and cancer samples. Clinical validation of both markers in cervical scrapings from patients with an abnormal cervical smear confirmed that frequency and relative level of methylation were related with increasing severity of the underlying CIN lesion and that ROC analysis was discriminative. These markers represent the COL25A1 and KATNAL2 and their observed increased methylation upon progression could intimate the regulatory role in carcinogenesis. In conclusion, our newly identified hypermethylated DMRs represent specific DNA methylation patterns in high-grade CIN lesions and are candidate biomarkers for early detection.

  6. Oncocytoma-Like Renal Tumor With Transformation Toward High-Grade Oncocytic Carcinoma (United States)

    Sirintrapun, Sahussapont J.; Geisinger, Kim R.; Cimic, Adela; Snow, Anthony; Hagenkord, Jill; Monzon, Federico; Legendre, Benjamin L.; Ghazalpour, Anatole; Bender, Ryan P.; Gatalica, Zoran


    Abstract Renal oncocytoma is a benign tumor with characteristic histologic findings. We describe an oncocytoma-like renal tumor with progression to high-grade oncocytic carcinoma and metastasis. A 74-year-old man with no family history of cancer presented with hematuria. Computed tomography showed an 11 cm heterogeneous multilobulated mass in the right kidney lower pole, enlarged aortocaval lymph nodes, and multiple lung nodules. In the nephrectomy specimen, approximately one third of the renal tumor histologically showed regions classic for benign oncocytoma transitioning to regions of high-grade carcinoma without sharp demarcation. With extensive genomic investigation using single nucleotide polymorphism-based array virtual karyotyping, multiregion sequencing, and expression array analysis, we were able to show a common lineage between the benign oncocytoma and high-grade oncocytic carcinoma regions in the tumor. We were also able to show karyotypic differences underlying this progression. The benign oncocytoma showed no chromosomal aberrations, whereas the high-grade oncocytic carcinoma showed loss of the 17p region housing FLCN (folliculin [Birt–Hogg–Dubé protein]), loss of 8p, and gain of 8q. Gene expression patterns supported dysregulation and activation of phosphoinositide 3-kinase (PI3K)/v-akt murine thymoma viral oncogene homolog (Akt), mitogen-activated protein kinase (MAPK)/extracellular-signal-regulated kinase (ERK), and mechanistic target of rapamycin (serine/threonine kinase) (mTOR) pathways in the high-grade oncocytic carcinoma regions. This was partly attributable to FLCN underexpression but further accentuated by overexpression of numerous genes on 8q. In the high-grade oncocytic carcinoma region, vascular endothelial growth factor A along with metalloproteinases matrix metallopeptidase 9 and matrix metallopeptidase 12 were overexpressed, facilitating angiogenesis and invasiveness. Genetic molecular testing provided evidence for the

  7. Evidence of nerve sheath differentiation and high grade morphology in sclerosing epithelioid fibrosarcoma (United States)

    Hanson, I; Pearson, J; Eyden, B; Slawik, S; Harris, M


    Sclerosing epithelioid fibrosarcoma is a recently described sarcoma in which ultrastructural evidence of fibroblastic differentiation forms part of the diagnostic criteria. This report describes a further case of this tumour, which showed evidence of both fibroblastic and perineurial differentiation by immunohistochemistry and electron microscopy, and which had areas of high grade morphology. The tumour metastasised and the patient died of disease 12 months after presentation. The relevance of these findings to diagnosis and differentiation in these tumours is discussed. Key Words: sclerosing epithelioid fibrosarcoma • nerve sheath differentiation • high grade morphology PMID:11533083

  8. Identifying patients at risk for high-grade intra-abdominal hypertension following trauma laparotomy. (United States)

    Strang, Steven G; Van Imhoff, Diederik L; Van Lieshout, Esther M M; D'Amours, Scott K; Van Waes, Oscar J F


    Abdominal Compartment Syndrome (ACS) is an uncommon but deleterious complication after trauma laparotomy. Early recognition of patients at risk of developing ACS is crucial for their outcome. The aim of this study was to compare the characteristics of patients who developed high-grade intra-abdominal hypertension (IAH) (i.e., grade III or IV; intra-abdominal pressure, IAP >20 mm Hg) following an injury-related laparotomy versus those who did not (i.e., IAP ≤20 mm Hg). A retrospective analysis of consecutive trauma patients admitted to a level 1 trauma centre in Australia between January 1, 1995 and January 31, 2010 was performed. A comparison was made between characteristics of patients who developed high-grade IAH following trauma laparotomy versus those who did not. A total of 567 patients (median age 31 years) were included in this study. Of these patients 10.2% (58/567) developed high-grade IAH of which 51.7% (30/58) developed ACS. Patients with high-grade IAH were older (pgrade IAH received larger volumes of crystalloids (pgrade IAH suffered higher mortality rates (25.9% (15/58) vs. 12.2% (62/509); p=0.012). Of all patients who underwent a trauma laparotomy, 10.2% developed high-grade IAH, which increases the risk of mortality. Patients with acidosis, coagulopathy, and hypothermia were especially at risk. In these patients, the abdomen should be left open until adequate resuscitation has been achieved, allowing for definitive surgery. This is a level III retrospective study. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Risk factors for high-grade envenomations after French viper bites in children. (United States)

    Claudet, Isabelle; Maréchal, Céline; Gurrera, Emmanuel; Cordier, Laurie; Honorat, Raphaele; Grouteau, Erick


    Viper bites and subsequent evolution to severe envenomations are more frequent in children. The aims of this study were to describe the clinical, biological, and therapeutic characteristics of children bitten by vipers in France and to identify risk factors associated with severe envenomations. A retrospective study was conducted between 2001 and 2009 in the pediatric emergency department of a tertiary-level children hospital. Collected data were age and sex of children; day and time of admission; day, time, and circumstances of the accident; snake identification; bite location; envenomation severity; presence of fang marks; prehospital care; use of specific immunotherapy and associated treatments; length of stay; and hospital course. Fifty-eight children were included (43 boys, 15 girls). The mean age was 7.8 ± 4.1 years. Bites were most often located on the lower extremities (77%). The classification of envenomation was: 83% low grade (absence or minor envenomation) and 17% high-grade (moderate to severe envenomations). All high-grade envenomations received specific immunotherapy (Viperfav). Being bitten on an upper extremity (P level (P = 0.016) were associated with a significant risk of high-grade envenomation. In the multivariate analysis, 3 factors remained significant: upper-extremity location (relative risk [RR], 60.5 [3.5-1040]; P = 0.005), immediate violent pain (RR, 21.5 [1.3-364.5]; P = 0.03), and female sex (RR, 17.5 [0.9-320.3]; P = 0.053). A certain number of criteria seem related to more significant risk of progression to high-grade envenomation. Bites to the upper extremities should be carefully observed because of the risk of evolution to a high-grade envenomation.

  10. Effect of High-Grade Preoperative Knee Laxity on Anterior Cruciate Ligament Reconstruction Outcomes. (United States)

    Magnussen, Robert A; Reinke, Emily K; Huston, Laura J; Hewett, Timothy E; Spindler, Kurt P


    Knee laxity in the setting of suspected anterior cruciate ligament (ACL) injury is frequently assessed through physical examination using the Lachman, pivot-shift, and anterior drawer tests. The degree of laxity noted on these examinations may influence treatment decisions and prognosis. Increased preoperative knee laxity would be associated with increased risk of subsequent revision ACL reconstruction and worse patient-reported outcomes 2 years postoperatively. Cohort study; Level of evidence, 2. From an ongoing prospective cohort study, 2333 patients who underwent primary isolated ACL reconstruction without collateral or posterior cruciate ligament injury were identified. Patients reported by the operating surgeons as having an International Knee Documentation Committee (IKDC) grade D for Lachman, anterior drawer, or pivot-shift examination were classified as having high-grade laxity. Multiple logistic regression modeling was used to evaluate whether having high-grade preoperative laxity was associated with increased odds of undergoing revision ACL reconstruction within 2 years of the index procedure, controlling for patient age, sex, Marx activity level, level of competition, and graft type. Multiple linear regression modeling was used to evaluate whether having high-grade preoperative laxity was associated with worse IKDC score or Knee injury and Osteoarthritis Outcome Score Knee-Related Quality of Life subscale (KOOS-QOL) scores at a minimum 2 years postoperatively, controlling for baseline score, patient age, ethnicity, sex, body mass index, marital status, smoking status, sport participation, competition level, Marx activity rating score, graft type, and articular cartilage and meniscus status. Pre-reconstruction laxity data were available for 2325 patients (99.7%). Two-year revision data were available for 2259 patients (96.8%), and patient-reported outcomes were available for 1979 patients (84.8%). High-grade preoperative laxity was noted in 743 patients

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

    Directory of Open Access Journals (Sweden)

    Jian-jun Sun


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

  12. Treatment of High-Grade Anal Dysplasia in High Risk Patients: Outcome at an Urban Community Health Center (United States)

    Assoumou, Sabrina Annick; Panther, Lori Ann; Feng, Yang; Gelman, Rebecca Sue; Fugelso, Dana Kailani; Mayer, Kenneth Hugh


    SUMMARY Human immunodeficiency (HIV)-infected patients and men who have sex with men (MSM) have a higher rate of high-grade anal intraepithelial neoplasia (HGAIN), a likely precursor to anal cancer. This retrospective study describes the outcome of treating MSM with incident biopsy-proven HGAIN in an urban community health setting with access to outpatient ablation or operative treatment. The main outcome was freedom from HGAIN at follow-up. 153 met inclusion criteria; 86 (56%) were HIV-infected. Eighty (52%) received outpatient ablation, 49(61%) had a follow-up within 9 months. Among those, 26 (53%) were free of high-grade disease, 19 (39%) had high-grade disease; and 4 (8%) had unknown grading. In a logistic regression model, a lower extent of anal disease (1 quadrant vs. 2,3, or 4 quadrants) was significantly associated with a lower probability of high-grade disease (p-value 0.04.) HGAIN could be managed in a community health setting; however, systems are needed to ensure follow-up care. PMID:23535356

  13. Predicting Freshman Grade Point Average From College Admissions Test Scores and State High School Test Scores


    Daniel Koretz; Carol Yu; Preeya P. Mbekeani; Meredith Langi; Tasmin Dhaliwal; David Braslow


    The current focus on assessing “college and career readiness” raises an empirical question: How do high school tests compare with college admissions tests in predicting performance in college? We explored this using data from the City University of New York and public colleges in Kentucky. These two systems differ in the choice of college admissions test, the stakes for students on the high school test, and demographics. We predicted freshman grade point average (FGPA) from high school GPA an...

  14. Grade Inflation. (United States)

    Taylor, Hugh

    Grade inflation is discussed, and some solutions are offered for the grade inflation problem which exists in the Faculty of Education at the University of Victoria, British Columbia. Examples illustrate the existence of grade inflation at several colleges and universities, as well as at the high school level. Various reactions--involving college…

  15. The Impact of High-Speed Internet Connectivity at Home on Eighth-Grade Student Achievement (United States)

    Kingston, Kent J.


    In the fall of 2008 Westside Community Schools - District 66, in Omaha, Nebraska implemented a one-to-one notebook computer take home model for all eighth-grade students. The purpose of this study was to determine the effect of a required yearlong one-to-one notebook computer program supported by high-speed Internet connectivity at school on (a)…

  16. Over-expression of β-catenin is associated with high grade of ...

    African Journals Online (AJOL)

    W. Said


    Apr 28, 2017 ... a Department of Pathology, Faculty of Medicine, University of Benghazi, Benghazi, Libya b Department of Urology, ... by 2030 basically due to the growth and aging of the global population [1]. .... Over-expression of ß-catenin is associated with high grade of prostatic cancer in Libyan patients. 135. Table 1.

  17. High School Grade Inflation from 2004 to 2011. ACT Research Report Series, 2013 (3) (United States)

    Zhang, Qian; Sanchez, Edgar I.


    This study explores inflation in high school grade point average (HSGPA), defined as trend over time in the conditional average of HSGPA, given ACT® Composite score. The time period considered is 2004 to 2011. Using hierarchical linear modeling, the study updates a previous analysis of Woodruff and Ziomek (2004). The study also investigates…

  18. Fluctuating fetal or neonatal renal pelvis: marker of high-grade vesicoureteral reflux. (United States)

    Anderson, Nigel G; Allan, Richard B; Abbott, George D


    Fetal renal pelvic dilatation is a predictor of vesicoureteral reflux (VUR), but has low specificity. The aim of this study was to determine the clinical significance of fluctuating size of the renal pelvis on sonography, particularly in relationship to VUR. We prospectively recorded fetal renal pelvic diameter >/=4 mm in 1,092 fetuses (692 boys), from May 1989 to December 1995, with a minimum follow-up of 7 years. Fluctuation, defined as size of renal pelvis changing by more than 4 mm during the course of obstetric (23), postnatal (128), and both pre- and postnatal (7) renal sonograms, was recorded prospectively in 159 (117 boys). Of the 1,092, 849 (593 boys) had a voiding cystourethrogram at a mean age of 7 weeks (range 3-20 weeks). Of the 31 (16 girls) with high-grade VUR, fluctuation was observed in 20 (9 girls). Fluctuation was strongly associated with high-grade VUR (odds ratio 11.1, P=0.0000003) and with renal damage (sensitivity 61%, positive predictive value 31%). Primary high-grade VUR was persistent, seen equally in boys and girls, and required surgery in the majority. Fluctuation was associated with renal duplication anomalies ( P=0.00009) and megaureter ( P<0.00000001). Fluctuation of the renal pelvis on sonography is a marker for persistent high-grade VUR and renal damage in girls and boys.

  19. Organizing the Cellular and Molecular Heterogeneity in High-Grade Serous Ovarian Cancer by Mass Cytometry (United States)

    Tumor heterogeneity in high grade serous ovarian cancer (HG-SOC) represents a significant barrier for successful therapeutic intervention. To further...understand the cell types contributing to this heterogeneity we performed a comprehensive phenotypic characterization of 22 primary ovarian tumor...also showed greater overall phenotypic heterogeneity quantified by Simpsons Diversity Index. Importantly the novel cell types identified have the

  20. Profiles of Genomic Instability in High-Grade Serous Ovarian Cancer Predict Treatment Outcome

    DEFF Research Database (Denmark)

    Wang, Zhigang C.; Birkbak, Nicolai Juul; Culhane, Aedín C.


    Purpose: High-grade serous cancer (HGSC) is the most common cancer of the ovary and is characterized by chromosomal instability. Defects in homologous recombination repair (HRR) are associated with genomic instability in HGSC, and are exploited by therapy targeting DNA repair. Defective HRR cause...

  1. L5 pedicle subtraction osteotomy for high-grade isthmic spondylolisthesis. (United States)

    Radcliff, Kristen E; Jakoi, Andre M


    To the authors' knowledge, this is the first article to present a pedicle subtraction osteotomy in the lumbar spine to correct and stabilize a high-grade isthmic spondylolisthesis, which poses many challenges with regard to treatment options and outcomes. The optimal surgical treatment for high-grade spondylolisthesis is controversial, but the goals of treatment are to stabilize the affected spinal levels and to decompress the neural elements. A pedicle subtraction osteotomy is a reconstructive procedure that addresses fixed sagittal imbalance by increasing lumbar lordosis through posterior spinal column shortening. The authors report a 46-year-old patient with chronic, progressively worsening back and leg radiculopathy accompanied by sagittal plane malalignment and for which a pedicle subtraction osteotomy was performed. The procedure yielded stabilization of the patient's lumbar spondylolisthesis and sagittal plane alignment was restoration. At 3 months postoperatively, the patient's pain had fully resolved and her motor and neurologic examination exhibited no deficits. At 24 months postoperatively, she was still symptom-free and ambulating without assistance. This report is the first documented successful pedicle subtraction osteotomy in the treatment of high-grade spondylolisthesis. This report indicates that certain patient populations may be amenable to pedicle subtraction osteotomy as a treatment option for pathology involving high-grade isthmic spondylolisthesis. Copyright 2015, SLACK Incorporated.

  2. Residual high-grade stenosis after recanalization of extracranial carotid occlusion in acute ischemic stroke

    NARCIS (Netherlands)

    Luitse, M.J.; Velthuis, B.K.; Dauwan, M.; Dankbaar, J.W.; Biessels, G.J.; Kappelle, L.J.; Meijer, F.J.; Dijk, E.J. van


    BACKGROUND AND PURPOSE: Residual stenosis after recanalization of an acute symptomatic extracranial occlusion of the internal carotid artery (ICA) might be an indication for carotid endarterectomy. We evaluated the proportion of residual high-grade stenosis (>/=70%, near occlusions not included)

  3. 5-Aminolevulinic acid fluorescence in high grade glioma surgery: surgical outcome, intraoperative findings, and fluorescence patterns. (United States)

    Della Puppa, Alessandro; Ciccarino, Pietro; Lombardi, Giuseppe; Rolma, Giuseppe; Cecchin, Diego; Rossetto, Marta


    5-Aminolevulinic acid (5-ALA) fluorescence is a validated technique for resection of high grade gliomas (HGG); the aim of this study was to evaluate the surgical outcome and the intraoperative findings in a consecutive series of patients. Clinical and surgical data from patients affected by HGG who underwent surgery guided by 5-ALA fluorescence at our Department between June 2011 and February 2014 were retrospectively evaluated. Surgical outcome was evaluated by assessing the resection rate as gross total resection (GTR) > 98% and GTR > 90%. We finally stratified data for recurrent surgery, tumor location, tumor size, and tumor grade (IV versus III grade sec. WHO). 94 patients were finally enrolled. Overall GTR > 98% and GTR > 90% was achieved in 93% and 100% of patients. Extent of resection (GTR > 98%) was dependent on tumor location, tumor grade (P < 0.05), and tumor size (P < 0.05). In 43% of patients the boundaries of fluorescent tissue exceeded those of tumoral tissue detected by neuronavigation, more frequently in larger (57%) (P < 0.01) and recurrent (60%) tumors. 5-ALA fluorescence in HGG surgery enables a GTR in 100% of cases even if selection of patients remains a main bias. Recurrent surgery, and location, size, and tumor grade can predict both the surgical outcome and the intraoperative findings.

  4. 5-Aminolevulinic Acid Fluorescence in High Grade Glioma Surgery: Surgical Outcome, Intraoperative Findings, and Fluorescence Patterns

    Directory of Open Access Journals (Sweden)

    Alessandro Della Puppa


    Full Text Available Background. 5-Aminolevulinic acid (5-ALA fluorescence is a validated technique for resection of high grade gliomas (HGG; the aim of this study was to evaluate the surgical outcome and the intraoperative findings in a consecutive series of patients. Methods. Clinical and surgical data from patients affected by HGG who underwent surgery guided by 5-ALA fluorescence at our Department between June 2011 and February 2014 were retrospectively evaluated. Surgical outcome was evaluated by assessing the resection rate as gross total resection (GTR>98% and GTR>90%. We finally stratified data for recurrent surgery, tumor location, tumor size, and tumor grade (IV versus III grade sec. WHO. Results. 94 patients were finally enrolled. Overall GTR>98% and GTR>90% was achieved in 93% and 100% of patients. Extent of resection (GTR>98% was dependent on tumor location, tumor grade (P<0.05, and tumor size (P<0.05. In 43% of patients the boundaries of fluorescent tissue exceeded those of tumoral tissue detected by neuronavigation, more frequently in larger (57% (P<0.01 and recurrent (60% tumors. Conclusions. 5-ALA fluorescence in HGG surgery enables a GTR in 100% of cases even if selection of patients remains a main bias. Recurrent surgery, and location, size, and tumor grade can predict both the surgical outcome and the intraoperative findings.

  5. Quantitative multi-modal MR imaging as a non-invasive prognostic tool for patients with recurrent low-grade glioma. (United States)

    Neill, Evan; Luks, Tracy; Dayal, Manisha; Phillips, Joanna J; Perry, Arie; Jalbert, Llewellyn E; Cha, Soonmee; Molinaro, Annette; Chang, Susan M; Nelson, Sarah J


    Low-grade gliomas can vary widely in disease course and therefore patient outcome. While current characterization relies on both histological and molecular analysis of tissue resected during surgery, there remains high variability within glioma subtypes in terms of response to treatment and outcome. In this study we hypothesized that parameters obtained from magnetic resonance data would be associated with progression-free survival for patients with recurrent low-grade glioma. The values considered were derived from the analysis of anatomic imaging, diffusion weighted imaging, and (1)H magnetic resonance spectroscopic imaging data. Metrics obtained from diffusion and spectroscopic imaging presented strong prognostic capability within the entire population as well as when restricted to astrocytomas, but demonstrated more limited efficacy in the oligodendrogliomas. The results indicate that multi-parametric imaging data may be applied as a non-invasive means of assessing prognosis and may contribute to developing personalized treatment plans for patients with recurrent low-grade glioma.

  6. Palbociclib Isethionate in Treating Younger Patients With Recurrent, Progressive, or Refractory Central Nervous System Tumors (United States)


    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

  7. High grade neuroendocrine lung tumors: pathological characteristics, surgical management and prognostic implications. (United States)

    Grand, Bertrand; Cazes, Aurélie; Mordant, Pierre; Foucault, Christophe; Dujon, Antoine; Guillevin, Elizabeth Fabre; Barthes, Françoise Le Pimpec; Riquet, Marc


    Among non-small cell lung cancers (NSCLC), large cell carcinoma (LCC) is credited of significant adverse prognosis. Its neuroendocrine subtype has even a poorer diagnosis, with long-term survival similar to small cell lung cancer (SCLC). Our purpose was to review the surgical characteristics of those tumors. The clinical records of patients who underwent surgery for lung cancer in two French centers from 1980 to 2009 were retrospectively reviewed. We more particularly focused on patients with LCC or with high grade neuroendocrine lung tumors. High grade neuroendocrine tumors were classified as pure large cell neuroendocrine carcinoma (pure LCNEC), NSCLC combined with LCNEC (combined LCNEC), and SCLC combined with LCNEC (combined SCLC). There were 470 LCC and 155 high grade neuroendocrine lung tumors, with no difference concerning gender, mean age, smoking habits. There were significantly more exploratory thoracotomies in LCC, and more frequent postoperative complications in high grade neuroendocrine lung tumors. Pathologic TNM and 5-year survival rates were similar, with 5-year ranging from 34.3% to 37.6% for high grade neuroendocrine lung tumors and LCC, respectively. Induction and adjuvant therapy were not associated with an improved prognosis. The subgroups of LCNEC (pure NE, combined NE) and combined SCLC behaved similarly, except visceral pleura invasion, which proved more frequent in combined NE and less frequent in combined SCLC. Survival analysis showed a trend toward a lower 5-year survival in case of combined SCLC. Therefore, LCC, LCNEC and combined SCLC share the same poor prognosis, but surgical resection is associated with long-term survival in about one third of patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. Active MMP-2 Activity Discriminates Colonic Mucosa, Adenomas with and without High Grade Dysplasia and Cancers (United States)

    Murnane, Mary Jo; Cai, Jinguo; Shuja, Sania; McAneny, David; Willett, John B.


    Pathologic assessment of colorectal adenomas, a complex task with significant inter-observer variability, typically defines the scheduling of surveillance colonoscopies following removal of adenomas. We have characterized the activity levels of pro- and active matrix metalloproteinase-2 and matrix metalloproteinase-9 in colorectal adenomas and carcinomas, as potential markers of pathologic progression during colorectal tumorigenesis. Endogenous fully activated matrix metalloproteinase-2, in particular, has been studied less frequently in adenomas due to difficulties in detection. For this report, tissues (n=119) from 51 individuals were extracted and assayed on gelatin zymograms with digital standardization to nanogram quantities of purified active controls. Resulting data were assessed by graphical and multinomial logit regression analyses to test whether matrix metalloproteinase-2 or matrix metalloproteinase-9 activities could discriminate among four different types of colorectal tissue (normal mucosa, adenomas with or without high grade dysplasia and invasive carcinomas). Active matrix metalloproteinase-2 successfully discriminated among these tissue categories. Median activity for active matrix metalloproteinase-2 increased in a stepwise fashion with pathologic progression from normal mucosa to adenoma without high grade dysplasia to adenoma with high grade dysplasia to cancer. Although pro-matrix metalloproteinase-2 and pro-matrix metalloproteinase-9 activities could discriminate to some extent among tissue categories, those effects did not contribute additional information. Active matrix metalloproteinase-2 activity correlated significantly with histopathologic assessment of colorectal tissues. The ability of active matrix metalloproteinase-2 to distinguish adenomas with high grade dysplasia from adenomas without high grade dysplasia may be particularly useful in predicting future colorectal cancer risk for an individual, thus optimizing scheduling of

  9. Targeting the MAP kinase pathway in astrocytoma cells using a recombinant anthrax lethal toxin as a way to inhibit cell motility and invasion. (United States)

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


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

  10. Differences in the architecture of low-grade and high-grade gliomas evaluated using fiber density index and fractional anisotropy. (United States)

    Chen, Yiyong; Shi, Yonghong; Song, Zhijian


    Accurate pre-operative assessment of tumor grade is important for the selection of appropriate treatment strategies. The aim of this study was to retrospectively evaluate whether the fiber density index (FDi) and fractional anisotropy (FA) via diffusion tensor MRI (DTI) could assist with pre-operative diagnosis of glioma grade. A total of 31 patients who had histologically confirmed gliomas underwent DTI performed using a 1.5-Tesla magnetic resonance scanner. To reconstruct the white matter adjacent to the tumor, DTI fiber tracking (DTI-FT) using an FA threshold of 0.15 was implemented. Regions of interest (ROIs) were defined (i-iv) as: the tumor center (ROI i); white matter adjacent to the tumor (ROI ii); contralateral centrum semiovale (ROI iii); and the homologous fiber tracts to ROI ii in the contralateral hemisphere (ROI iv). We calculated six parameters from different ROIs and compared high-grade and low-grade gliomas: FA values and ratios; FDi values and ratios with an FA threshold of 0.15; and FDi values and ratios with an FA threshold of 0.25. The results showed that FA ratios and FDi ratios with FA thresholds of 0.25 were significantly different between patients with high-grade and low-grade gliomas. This may be useful for developing surgical strategies and appraising patient prognosis.

  11. Textural analysis of pre-therapeutic [18F]-FET-PET and its correlation with tumor grade and patient survival in high-grade gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Pyka, Thomas; Hiob, Daniela; Wester, Hans-Juergen [Klinikum Rechts der Isar der TU Muenchen, Department of Nuclear Medicine, Munich (Germany); Gempt, Jens; Ringel, Florian; Meyer, Bernhard [Klinikum Rechts der Isar der TU Muenchen, Neurosurgic Department, Munich (Germany); Schlegel, Juergen [Klinikum Rechts der Isar der TU Muenchen, Institute of Pathology and Neuropathology, Munich (Germany); Bette, Stefanie [Klinikum Rechts der Isar der TU Muenchen, Neuroradiologic department, Munich (Germany); Foerster, Stefan [Klinikum Rechts der Isar der TU Muenchen, Department of Nuclear Medicine, Munich (Germany); Klinikum Rechts der Isar der TU Muenchen, TUM Neuroimaging Center (TUM-NIC), Munich (Germany)


    Amino acid positron emission tomography (PET) with [18F]-fluoroethyl-L-tyrosine (FET) is well established in the diagnostic work-up of malignant brain tumors. Analysis of FET-PET data using tumor-to-background ratios (TBR) has been shown to be highly valuable for the detection of viable hypermetabolic brain tumor tissue; however, it has not proven equally useful for tumor grading. Recently, textural features in 18-fluorodeoxyglucose-PET have been proposed as a method to quantify the heterogeneity of glucose metabolism in a variety of tumor entities. Herein we evaluate whether textural FET-PET features are of utility for grading and prognostication in patients with high-grade gliomas. One hundred thirteen patients (70 men, 43 women) with histologically proven high-grade gliomas were included in this retrospective study. All patients received static FET-PET scans prior to first-line therapy. TBR (max and mean), volumetric parameters and textural parameters based on gray-level neighborhood difference matrices were derived from static FET-PET images. Receiver operating characteristic (ROC) and discriminant function analyses were used to assess the value for tumor grading. Kaplan-Meier curves and univariate and multivariate Cox regression were employed for analysis of progression-free and overall survival. All FET-PET textural parameters showed the ability to differentiate between World Health Organization (WHO) grade III and IV tumors (p < 0.001; AUC 0.775). Further improvement in discriminatory power was possible through a combination of texture and metabolic tumor volume, classifying 85 % of tumors correctly (AUC 0.830). TBR and volumetric parameters alone were correlated with tumor grade, but showed lower AUC values (0.644 and 0.710, respectively). Furthermore, a correlation of FET-PET texture but not TBR was shown with patient PFS and OS, proving significant in multivariate analysis as well. Volumetric parameters were predictive for OS, but this correlation did not

  12. Prognostic value of endocervical sampling following loop excision of high grade intraepithelial neoplasia. (United States)

    Cui, Yiwen; Sangi-Haghpeykar, Haleh; Patsner, Bruce; Bump, Jennifer M M; Williams-Brown, Marian Y; Binder, Gary L; Masand, Ramya P; Anderson, Matthew L


    To assess the role of additional biopsies performed with loop electrosurgical excisional procedure (LEEP) in predicting the likelihood of persistent high grade intraepithelial neoplasia. Clinicopathologic data were abstracted from women who underwent excision of high grade intraepithelial lesions between 2001 and 2014. Persistent disease was defined as uninterrupted high grade intraepithelial neoplasia, whereas recurrent disease was defined as disease diagnosed ≥1year after treatment with intervening normal evaluation. Chi-square and Fisher's exact tests were used to examine associations between demographic and histologic parameters and clinical outcomes. A total of 606 women underwent LEEP for high grade intraepithelial neoplasia (HSIL), of whom, 178 (29%) were additionally evaluated by endocervical curettage, 80 (13%), top hat and 99 (16%), both procedures. With mean follow-up of 1.9±1.5years, persistent disease was identified in 87 women (14%) while recurrent disease was diagnosed in 20 (3%). After adjusting for age, HIV status and histologic grade of disease, the presence of disease at the endocervical margin (aOR=2.2, 95% CL 1.8-5.5, p<0.0001), with endocervical curettage (aOR=2.39, 95% CL 1.2-9.9, p=0.025) or on top hat (aOR=4.0, 95% CL 1.1-16.2, p=0.04) correlated with the likelihood of persistent but not recurrent disease. Only endocervical margin status remained predictive (p=0.03) of outcome after controlling for pre-procedure likelihood of endocervical disease. Sensitivity of endocervical margin status for persistent disease was 56.9% with specificity of 72.2%. Positive predictive value (PPV) was 24.9% and negative predictive value (NPV) 90.9%. Despite frequent use of additional procedures to sample the endocervix, these strategies do not improve the ability of endocervical margin status to predict persistent or recurrent dysplasia. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Liver stiffness measurement predicts high-grade post-hepatectomy liver failure: A prospective cohort study. (United States)

    Chong, Charing Ching-Ning; Wong, Grace Lai-Hung; Chan, Anthony Wing-Hung; Wong, Vincent Wai-Sun; Fong, Anthony Kwong-Wai; Cheung, Yue-Sun; Wong, John; Lee, Kit-Fai; Chan, Stephen L; Lai, Paul Bo-San; Chan, Henry Lik-Yuen


    Liver stiffness measurement using transient elastography appears to be an excellent tool for detection of liver fibrosis and cirrhosis with high accuracy. The aim of this study is to evaluate the efficacy of preoperative liver stiffness measurement in predicting post-hepatectomy liver failure. A prospective cohort study of all consecutive patients undergoing hepatectomy for hepatocellular carcinoma from February 2010 to August 2014 was studied. All patients received detailed preoperative assessments including liver stiffness measurement. The primary outcome was post-hepatectomy liver failure according to the International Study Group of Liver Surgery definition. A total of 255 patients were included. Liver stiffness measurement showed significant correlation with grade B or C post-hepatectomy liver failure. (P = 0.003) Using the cutoff at 12 kPa, liver stiffness measurement had a sensitivity of 52.4% and specificity of 73.3% in predication of high-grade (grade B or C) post-hepatectomy liver failure. Liver stiffness measurement > 12 kPa was also an independent prognostic factor for both high-grade post-hepatectomy liver failure and major postoperative complications by multivariate analysis. The diagnostic accuracy was better in patients without right lobe tumor with an area under the receiver operating characteristic of 0.83 compared with an area under the receiver operating characteristic of only 0.62 in patients with right lobe tumor. Liver stiffness measurement using Fibroscan is good to predict high-grade post-hepatectomy liver failure especially in patients without right lobe tumor. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  14. Epidemiologic Study on Drug Abuse among First and Second Grade High School Students in Kerman


    Nakhaee, Nouzar; Ziaaddini, Hassan; Karimzadeh, Ali


    Background: This study investigated the epidemiology of drug abuse among high school students in Kerman. Methods: This was a cross-sectional study on a randomly selected sample of 652 first and second grade high school students (256 boys, 396 girls) in Kerman. They were informed that their answers would be classified and nameless before they filled questionnaires. Schools and classes were selected using stratified sampling method. Findings: From total 652 students participated in this study, ...

  15. High efficiency, high modulation bandwidth (Ga,Al)As:Te,Zn light-emitting diodes with graded band gap (United States)

    Leibenzeder, S.; Rühle, W.; Hoffmann, L.; Weyrich, C.


    A new (Ga,Al)As light-emitting diode (λmax =660-880 nm) is presented which has several advantages: simple processing, high external quantum efficiencies (up to 12%), and short decay times (down to 12 ns). The importance of photon recycling and reduced self-absorption in the graded band gap is demonstrated.

  16. Body mass index, serum total cholesterol, and risk of gastric high-grade dysplasia (United States)

    Huang, Ya-Kai; Kang, Wei-Ming; Ma, Zhi-Qiang; Liu, Yu-Qin; Zhou, Li; Yu, Jian-Chun


    Abstract Obesity is related to an increased risk of gastric cardia cancer. However, the influences of excess body weight and serum total cholesterol on the risk of gastric high-grade dysplasia have not been fully characterized. A case–control study was conducted to explore the relationships between body mass index (BMI), serum total cholesterol level, and the risk of gastric high-grade dysplasia in Chinese adults. A total of 893 consecutive patients with gastric high-grade dysplasia (537 men and 356 women) and 902 controls (543 men and 359 women) were enrolled from January 2000 to October 2015. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated, and a multivariate analysis was conducted. After adjusting for age, alcohol consumption, smoking status, family history of gastric cancer or esophageal cancer, and serum total cholesterol level, a BMI ranging from 27.5 to 29.9 was significantly related to an increased risk of gastric high-grade dysplasia in both men (adjusted OR = 1.87, 95% CI = 1.24–2.81) and women (adjusted OR = 2.72, 95% CI = 1.44–5.16). The 2 highest BMI categories (27.5–29.9 and ≥30.0) were identified as risk factors for gastric cardia high-grade dysplasia in both men (BMI = 27.5–29.9: adjusted OR = 1.78, 95% CI = 1.02–3.10; BMI ≥ 30.0: adjusted OR = 2.54, 95% CI = 1.27–5.08) and women (BMI = 27.5–29.9: adjusted OR = 2.88, 95% CI = 1.27–6.55; BMI ≥ 30.0: adjusted OR = 2.77, 95% CI = 1.36–5.64), whereas only a BMI ranging from 27.5 to 29.9 was a risk factor for gastric noncardia high-grade dysplasia in both men (adjusted OR = 1.98, 95% CI = 1.25–3.14) and women (adjusted OR = 2.88, 95% CI = 1.43–5.81). In addition, higher serum total cholesterol was associated with an increased risk of gastric noncardia high-grade dysplasia (adjusted OR = 1.83, 95% CI = 1.25–2.69) in women. Increased BMI was associated with an increased risk

  17. Genome-wide ChIP-seq analysis of EZH2-mediated H3K27me3 target gene profile highlights differences between low- and high-grade astrocytic tumors. (United States)

    Sharma, Vikas; Malgulwar, Prit Benny; Purkait, Suvendu; Patil, Vikas; Pathak, Pankaj; Agrawal, Rahul; Kulshreshtha, Ritu; Mallick, Supriya; Julka, Pramod Kumar; Suri, Ashish; Sharma, Bhawani Shankar; Suri, Vaishali; Sharma, Mehar Chand; Sarkar, Chitra


    Enhancer of zeste homolog-2(EZH2) is a key epigenetic regulator that functions as oncogene and also known for inducing altered trimethylation of histone at lysine-27 (H3K27me3) mark in various tumors. However, H3K27me3 targets and their precise relationship with gene expression are largely unknown in astrocytic tumors. In this study, we checked EZH2 messenger RNA and protein expression in 90 astrocytic tumors of different grades using quantitative PCR and immunohistochemistry, respectively. Further, genome-wide ChIP-seq analysis for H3K27me3 modification was also performed on 11 glioblastomas (GBMs) and 2 diffuse astrocytoma (DA) samples. Our results showed EZH2 to be highly overexpressed in astrocytic tumors with a significant positive correlation with grade. Interestingly, ChIP-seq mapping revealed distinct differences in genes and pathways targeted by these H3K27me3 modifications between GBM versus DA. Neuroactive ligand receptor pathway was found most enriched in GBM (P = 9.4 × 10-25), whereas DA were found to be enriched in metabolic pathways. Also, GBM showed a higher enrichment of H3K27me3 targets reported in embryonic stem cells and glioma stem cells as compared with DAs. Our results show majority of these H3K27me3 target genes were downregulated, not only due to H3K27me3 modification but also due to concomitant DNA methylation. Further, H3K27me3 modification-associated gene silencing was not restricted to promoter but also present in gene body and transcription start site regions. To the best of our knowledge, this is the first high-resolution genome-wide mapping of H3K27me3 modification in adult astrocytic primary tissue samples of human, highlighting the differences between grades. Interestingly, we identified SLC25A23 as important target of H3K27me3 modification, which was downregulated in GBM and its low expression was associated with poor prognosis in GBMs. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions

  18. Urinary cytology with acridine orange fluorescence is highly valuable for predicting high-grade upper urinary tract urothelial carcinoma. (United States)

    Li, Jing; Zhang, Zhihong; Wang, Jin; Zhang, Changwen; Li, Haibo; Xu, Yong


    To evaluate the clinical value of acridine orange fluorescent staining in urinary cytology for the diagnosis of upper urinary tract urothelial carcinoma. A retrospective analysis was conducted with 510 cases of upper urinary tract urothelial carcinoma (UTUC) in terms of the results of acridine orange fluorescence (AO-F) staining of the exfoliated cells in urine. The percentage of positive AO-F result and the positive predictive value of AO-F for high-grade and muscle invasive urothelial carcinoma were calculated and analyzed in terms of clinical characteristics. The overall percentage of positive AO-F result was 49% in the 510 patients, 54.1% for males and 40.6% for females. AO-F was positive in 51.9% of the patients with hematuria and 36.2% of the patients without hematuria. AO-F was positive in 56.4% of the patients with renal pelvis carcinoma and 42.8% of the patients with ureteral cancer; in 44.6% of the patients with non-muscle invasive carcinoma and 53.5% of the patients with muscle-invasive carcinoma. AO-F was positive in 26.8% of the cases with low-grade carcinoma and 55.3% of the patients with high-grade carcinoma. The positive predictive value of AO-F was 88% for high-grade cancer, and only 53.6% for muscle invasive carcinoma. Acridine orange fluorescence microscopy cannot increase the sensitivity of urine exfoliative cytology in the diagnosis of UTUC. It may be used as a predictor of high-grade UTUC. Acridine orange fluorescence microscopy in urinary cytodiagnosis does not show high value in predicting muscle invasive UTUC.

  19. Aspecific inflammatory lesion (histiocytosis?) simulating intramedullary astrocytoma. Case report. (United States)

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


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


    Directory of Open Access Journals (Sweden)

    Srinivasa Rao


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

  1. Complications of high grade liver injuries: management and outcomewith focus on bile leaks

    Directory of Open Access Journals (Sweden)

    Bala Miklosh


    Full Text Available Abstract Background Although liver injury scale does not predict need for surgical intervention, a high-grade complex liver injury should alert the physician to expect an increased risk of hepatic complications following trauma. The aim of the current study was to define hepatic related morbidity in patients sustaining high-grade hepatic injuries that could be safely managed non-operatively. Patients and methods This is a retrospective study of patients with liver injury admitted to Hadassah-Hebrew University Medical Centre over a 10-year period. Grade 3-5 injuries were considered to be high grade. Collected data included the number and types of liver-related complications. Interventions which were required for these complications in patients who survived longer than 24 hours were analysed. Results Of 398 patients with liver trauma, 64 (16% were found to have high-grade liver injuries. Mechanism of injury was blunt trauma in 43 cases, and penetrating in 21. Forty patients (62% required operative treatment. Among survivors 22 patients (47.8% developed liver-related complications which required additional interventional treatment. Bilomas and bile leaks were diagnosed in 16 cases post-injury. The diagnosis of bile leaks was suspected with abdominal CT scan, which revealed intraabdominal collections (n = 6, and ascites (n = 2. Three patients had continuous biliary leak from intraabdominal drains left after laparotomy. Nine patients required ERCP with biliary stent placement, and 2 required percutaneous transhepatic biliary drainage. ERCP failed in one case. Four angioembolizations (AE were performed in 3 patients for rebleeding. Surgical treatment was found to be associated with higher complication rate. AE at admission was associated with a significantly higher rate of biliary complications. There were 24 deaths (37%, the majority from uncontrolled haemorrhage (18 patients. There were only 2 hepatic-related mortalities due to liver failure

  2. Impact of intraoperative MRI on the surgical results for high-grade gliomas. (United States)

    Hirschberg, H; Samset, E; Hol, P K; Tillung, T; Lote, K


    The impact of intraoperative MRI (iMRI) on the surgical procedure, patient outcome and median survival for a series of patients harbouring high-grade gliomas forms the basis of this study. Their outcome has been compared to a matched cohort of patients operated in a conventional manner to determine if the use of intraoperative MRI can be shown to improve the results of surgery and prognosis for this type of patient. 32 microsurgical open craniotomies, performed in the intraoperative iMRI scanner for grade IV supratentorial gliomas, with follow-up periods of more than 2 months, were analyzed for this study. A group of 32 primary high-grade glioma patients (no recurrent tumors) were matched for age, preoperative clinical grade, gender and histology and operated during a corresponding time interval in a conventional manner acted as controls. All 64 patients were examined and analyzed for the occurrence of postoperative increased neurological morbidity or death. No complications directly related to the intraoperative scanning procedures were observed and no intraoperative death occurred in either group. The average operating time in the intraoperative scanner was 5.1 hours and was significantly longer than in the conventional OR (3.4 hours). The mean overall survival time for the 32 patients in the study group was 14.5 months (95 % confidence interval 12.0 - 16.6) compared to 12.1 months (95 % confidence interval 10.2 - 14.1) for the matched control group. Although iMRI is an effective way of imaging residual tumor, this study could not demonstrate an increased efficacy of surgery utilizing this technique for patients harbouring grade IV gliomas compared to more conventional methods. No statistical significance was noted between the two groups (p = 0.14). The complication rate was within the range reported for other series, in both control as well as the study group.

  3. Minimal access bilateral transforaminal lumbar interbody fusion for high-grade isthmic spondylolisthesis. (United States)

    Quraishi, N A; Rampersaud, Y Raja


    Minimally invasive or "minimal access surgery" (MAS) is being utilized with increasing frequency to reduce approach-related morbidity in the lumbar spine. This paper describes our minimal access technique for posterior bilateral transforaminal lumbar interbody fusion (TLIF) and spinal instrumentation in a patient with high-grade spondylolisthesis grade (Myerding Grade III) with 5-year follow-up. A 24-year-old lady presented with mechanical back pain and left leg L5 radiculopathy. On examination, she was a thin lady with an obvious step deformity in the lower lumbar spine and otherwise, a normal neurological examination. Imaging showed a grade III isthmic L5-S1 spondylolisthesis with foraminal stenosis and focal kyphotic alignment of 20° [slip angle (SA) = 70°]. Conservative measures had failed, and a decision was made to proceed with a MAS-TLIF approach. The estimated blood loss was less than 100 ml, operating time 150 min, and post-operative hospital stay was 4 days. Post-operatively the patient had significant improvement of back and radicular pain. Improvement in ODI was substantial and sustained at 5 years. A solid fusion was achieved at 8 months. The slip percentage improved from 68 % (pre-op) to 28 % (post-op) and the focal alignment to 20° lordosis (SA = 110°). A MAS approach for selected patients with a mobile high-grade spondylolisthesis is feasible, safe and clinically effective, with the added benefit of reduced soft-tissue disruption. Our result of this technique suggests that the ability to correct focal deformity, and achieve excellent radiographic and clinical outcome is similar to the open procedure.

  4. Three meta-analyses define a set of commonly overexpressed genes from microarray datasets on astrocytomas. (United States)

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


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

  5. Increased incidence of penile cancer and high-grade penile intraepithelial neoplasia in Denmark 1978-2008

    DEFF Research Database (Denmark)

    Baldur-Felskov, Birgitte; Hannibal, Charlotte Gerd; Munk, Christian


    To assess the trends in incidence of penile cancer during 1978-2008 and high-grade penile intraepithelial neoplasia (PIN2/3) during 1998-2008 in Denmark.......To assess the trends in incidence of penile cancer during 1978-2008 and high-grade penile intraepithelial neoplasia (PIN2/3) during 1998-2008 in Denmark....

  6. High-grade dysplasia in sporadic fundic gland polyps : a case report and review of the literature

    NARCIS (Netherlands)

    Jalving, M; Koornstra, JJ; Gotz, JM; van der Waaij, LA; de Jong, S; Zwart, N; Karrenbeld, Arend; Kleibeuker, JH


    We present a case of fundic gland polyps (FGPs) containing high-grade dysplasia in a 68-year-old man. High-grade dysplasia, and even gastric adenocarcinoma, associated with FGPs have been described in patients with familial adenomatous polyposis (FAP) and attenuated familial adenomatous polyposis

  7. The use of 18F-FDG PET to differentiate progressive disease from treatment induced necrosis in high grade glioma

    NARCIS (Netherlands)

    Dankbaar, J. W.; Snijders, T. J.; Robe, P. A.; Seute, T.; Eppinga, W.; Hendrikse, J.; De Keizer, B.


    In the follow-up of patients treated for high grade glioma, differentiation between progressive disease (PD) and treatment-induced necrosis (TIN) is challenging. The purpose of this study is to evaluate the diagnostic accuracy of FDG PET for the differentiation between TIN and PD after high grade

  8. Comparable outcome between endometrioid and non-endometrioid tumors in patients with early-stage high-grade endometrial cancer

    NARCIS (Netherlands)

    Reynaers, E. A. E. M.; Ezendam, N. P. M.; Pijnenborg, J. M. A.


    Background Approximately 25% of endometrial cancer patients present with high-grade tumors. Unlike the clearly defined work-up for non-endometrioid endometrial cancer, no consensus exists for surgical staging and adjuvant therapy in high-grade endometrioid endometrial cancer. We compared the

  9. Comparable outcome between endometrioid and non-endometrioid tumors in patients with early-stage high-grade endometrial cancer

    NARCIS (Netherlands)

    Reynaers, E.A.; Ezendam, N.P.; Pijnenborg, J.M.A.


    BACKGROUND: Approximately 25% of endometrial cancer patients present with high-grade tumors. Unlike the clearly defined work-up for non-endometrioid endometrial cancer, no consensus exists for surgical staging and adjuvant therapy in high-grade endometrioid endometrial cancer. We compared the

  10. The Relationship of Mental Pressure with Optimism and Academic Achievement Motivation among Second Grade Male High School Students (United States)

    Sarouni, Ali Sedigh; Jenaabadi, Hossein; Pourghaz, Abdulwahab


    The present study aimed to examine the relationship of mental pressure with optimism and academic achievement motivation among second grade second period male high school students. This study followed a descriptive-correlational method. The sample included 200 second grade second period male high school students in Sooran. Data collection tools in…

  11. The Relative Predictive Validity of ACT Scores and High School Grades in Making College Admission Decisions. Issues in College Success (United States)

    ACT, Inc., 2008


    Postsecondary institutions often consider students' high school grades and ACT scores when making admission decisions. This issue brief summarizes ACT research on the relative weights of ACT scores and high school grades for predicting college persistence as well as selected indicators of academic success in college. (Contains 1 table and 3…

  12. Glioma Grading and Determination of IDH Mutation Status and ATRX loss by DCE and ASL Perfusion. (United States)

    Brendle, Cornelia; Hempel, Johann-Martin; Schittenhelm, Jens; Skardelly, Marco; Tabatabai, Ghazaleh; Bender, Benjamin; Ernemann, Ulrike; Klose, Uwe


    To evaluate arterial spin labeling (ASL) perfusion and dynamic contrast-enhanced (DCE) perfusion in glioma grading according to the previous WHO classification of 2007, as well as concerning isocitrate dehydrogenase (IDH) mutation status and ATRX expression as required by the new WHO 2016 brain tumor classification. The mean values of Ktrans, Kep, Ve, and Vp by DCE perfusion, and cerebral blood flow (CBF) by ASL perfusion were assessed retrospectively in 40 patients with initial glioma diagnosis. Perfusion parameters were correlated and compared concerning glioma grading, IDH mutation status and ATRX expression. The DCE and ASL perfusion parameters showed merely moderate correlation. The Ktrans, Ve, and CBF by DCE perfusion were different in low-grade and high-grade gliomas (p = 0.0018, p IDH mutation (p = 0.014, sensitivity = 0.75, specificity = 0.88) and showed a trend for the discrimination of astrocytomas with IDH mutation from oligodendrogliomas (p = 0.074). In conclusion, DCE and ASL perfusion are complementary in the differentiation of gliomas. The discrimination of low- and high-grade gliomas is possible by the DCE perfusion parameter Ve, while ASL perfusion shows potential for the differentiation of the IDH and ATRX mutation status of gliomas following the new WHO classification 2016. Both perfusion techniques might represent different aspects of brain tumor perfusion.

  13. Proposal for the award of two blanket contracts for the supply of high-grade helium

    CERN Document Server


    This document concerns the supply of up to 280 000 kg of high-grade helium. Following a call for tenders (IT-3235/AT) sent on 4 July 2003 to seven firms, in four Member States, CERN had, by the closing date, received six tenders from six firms in four Member States. The Finance Committee is invited to agree to the negotiation of two blanket contracts for the supply of up to 280 000 kg of high-grade helium with AIR PRODUCTS (FR) and CARBAGAS (CH) for a total maximum amount for both contracts of 5 577 800 US dollars (7 736 400 Swiss francs), not subject to revision, for a period of four years starting 1 January 2004. The rates of exchange used are those stipulated in the tenders. The firms have indicated the following distribution by country of the contract value covered by this adjudication proposal: AIR PRODUCTS : PL - 100%; CARBAGAS : PL - 100%.

  14. Forming high-efficiency silicon solar cells using density-graded anti-reflection surfaces (United States)

    Yuan, Hao-Chih; Branz, Howard M.; Page, Matthew R.


    A method (50) is provided for processing a graded-density AR silicon surface (14) to provide effective surface passivation. The method (50) includes positioning a substrate or wafer (12) with a silicon surface (14) in a reaction or processing chamber (42). The silicon surface (14) has been processed (52) to be an AR surface with a density gradient or region of black silicon. The method (50) continues with heating (54) the chamber (42) to a high temperature for both doping and surface passivation. The method (50) includes forming (58), with a dopant-containing precursor in contact with the silicon surface (14) of the substrate (12), an emitter junction (16) proximate to the silicon surface (14) by doping the substrate (12). The method (50) further includes, while the chamber is maintained at the high or raised temperature, forming (62) a passivation layer (19) on the graded-density silicon anti-reflection surface (14).

  15. Forming high efficiency silicon solar cells using density-graded anti-reflection surfaces (United States)

    Yuan, Hao-Chih; Branz, Howard M.; Page, Matthew R.


    A method (50) is provided for processing a graded-density AR silicon surface (14) to provide effective surface passivation. The method (50) includes positioning a substrate or wafer (12) with a silicon surface (14) in a reaction or processing chamber (42). The silicon surface (14) has been processed (52) to be an AR surface with a density gradient or region of black silicon. The method (50) continues with heating (54) the chamber (42) to a high temperature for both doping and surface passivation. The method (50) includes forming (58), with a dopant-containing precursor in contact with the silicon surface (14) of the substrate (12), an emitter junction (16) proximate to the silicon surface (14) by doping the substrate (12). The method (50) further includes, while the chamber is maintained at the high or raised temperature, forming (62) a passivation layer (19) on the graded-density silicon anti-reflection surface (14).

  16. Invisible gold and arsenic in pyrite from the high-grade Hishikari gold deposit, Japan (United States)

    Morishita, Y.; Shimada, N.; Shimada, K.


    Gold occurs as both electrum (a natural alloy of gold and silver) and invisible gold in arsenian pyrite in the Hishikari epithermal gold deposit in Japan. Microanalyses of arsenian pyrite from the deposit using secondary ion mass spectrometry (SIMS) and electron probe microanalysis (EPMA) revealed that Au concentrations (0.1-2600 ppm) are positively correlated with As concentrations (0.0-6.1%). A small (3 μm) area of pyrite was analyzed because the sample textures were fine and complicated. The Au/As ratio is high in the Sanjin ore zone, which has very high-grade veins, while the ratio is low in the Yamada ore zone, which has average-grade veins.

  17. High grade hemangioendothelioma of the temporal bone in a child: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyo Lim; Im, Soo Ah; Lim, Gye Yeon; Chun, Ho Jong; Lee, Hee Jeong; Park, Hyun Jin; Byun, Jae Young [The Catholic University of Korea, College of Medicine, Seoul (Korea, Republic of)


    Hemangioendothelioma is a rare vascular tumor characterized by endothelial tumor cells and variable malignant behavior, and it's not common for this lesion to involve the bone. Although there are a few reports of cranial involvement by hemangioendothelioma, only rare cases arising in temporal bone have been published. We present the radiologic findings of a 7-year-old boy who had a high grade hemangioendothelioma involving the temporal bone with intracranial extension. Evidence of flow voids on MR images suggested a tumor of vascular origin, and the ill-defined margins, cortical destruction and intracranial extension on the CT and MR images were correlated with the tumor's high histologic grade.

  18. P-COMM-B induction chemotherapy in intermediate and high grade non-Hodgkin's lymphoma. (United States)

    Phillips, J K; Sherlaw-Johnson, C; Davies, J M; Clough, J V; Parry, H; Nash, J R; Cawley, J C


    57 patients with newly diagnosed intermediate or high grade non-Hodgkin's lymphoma with stage II to IV disease were treated with P-COMM-B (prednisolone, cyclophosphamide, vincristine, mitozantrone, methotrexate and bleomycin). 46% patients achieved a complete remission and 26% achieved a partial remission. Projected disease-free survival in complete remission at 5 years is 56% and projected overall survival at 5 years is 37%. Neutropenia and proximal myopathy were the commonest severe toxicities encountered and two deaths were clearly related to treatment (3.5%). P-COMM-B is effective first-line chemotherapy in intermediate and high grade non-Hodgkin's lymphoma. The efficacy and toxicity of P-COMM-B appear to be comparable to those of the best contemporary regimen, CHOP.

  19. BRCA and early events in the development of high grade serous ovarian cancer

    Directory of Open Access Journals (Sweden)

    Sophia HL George


    Full Text Available Women who have an inherited mutation in the BRCA1 or BRCA2 genes have a substantial increased lifetime risk of developing epithelial ovarian cancer, and epidemiological factors related to parity, ovulation and hormone regulation have a dramatic effect on the risk in both BRCA mutation carriers and non-carriers. The most common and most aggressive histotype of epithelial ovarian cancer, high-grade serous carcinoma, is also the histotype associated with germline BRCA mutations. In recent years, evidence has emerged indicating that the likely tissue of origin of high-grade serous carcinoma is the fallopian tube. We have reviewed what is known about the fallopian tube in BRCA mutation carriers at both the transcriptional and translational aspect of their biology. We propose that changes of the transcriptome in BRCA heterozygotes reflect an altered response to the ovulatory stresses from microenvironment, which may include the post-ovulation inflammatory response and altered reproductive hormone physiology.

  20. Rare earth element patterns in Archean high-grade metasediments and their tectonic significance (United States)

    Taylor, Stuart Ross; Rudnick, Roberta L.; Mclennan, Scott M.; Eriksson, Kenneth A.


    REE data on metasedimentary rocks from two different types of high-grade Archean terrains are presented and analyzed. The value of REEs as indicators of crustal evolution is explained; the three geologic settings (in North America, Southern Africa, and Australia) from which the samples were obtained are described; and the data are presented in extensive tables and graphs and discussed in terms of metamorphic effects, the role of accessory phases, provenance, and tectonic implications (recycling, the previous extent of high-grade terrains, and a model of Archean crustal growth). The diversity of REE patterns in shallow-shelf metasediments is attributed to local provenance, while the Eu-depleted post-Archean patterns are associated with K-rich plutons from small, stable early Archean terrains.

  1. Immunotherapy for high-grade glioma: how to go beyond Phase I/II clinical trials. (United States)

    van Gool, Stefaan


    Evaluation of: Lasky JL 3rd, Panosyan EH, Plant A et al. Autologous tumor lysate-pulsed dendritic cell immunotherapy for pediatric patients with newly diagnosed or recurrent high-grade gliomas. Anticancer Res. 33, 2047-2056 (2013). Immunotherapy for children and adults with high-grade glioma (HGG) is an emerging innovative treatment approach, which aims at stimulating the body's own immune system against HGG by using autologous dendritic cells pulsed with autologous tumor lysate as a therapeutic vaccine. This is the third report on immunotherapy for HGG in children, bringing additional knowledge and experience to the scientific community. However, at the same time, this and other manuscripts urge for the next step in treatment development.

  2. Characterization of Pure Ductal Carcinoma In Situ on Dynamic Contrast-Enhanced MR Imaging: Do Nonhigh Grade and High Grade Show Different Imaging Features?

    Directory of Open Access Journals (Sweden)

    Siwa Chan


    Full Text Available To characterize imaging features of pure DCIS on dynamic contrast-enhanced MR imaging (DCE-MRI, 31 consecutive patients (37-81 years old, mean 56, including 2 Grade I, 16 Grade II, and 13 Grade III, were studied. MR images were reviewed retrospectively and the morphological appearances and kinetic features of breast lesions were categorized according to the ACR BI-RADS breast MRI lexicon. DCE-MRI was a sensitive imaging modality in detecting pure DCIS. MR imaging showed enhancing lesions in 29/31 (94% cases. Pure DCIS appeared as mass type or non-mass lesions on MRI with nearly equal frequency. The 29 MR detected lesions include 15 mass lesions (52%, and 14 lesions showing non-mass-like lesions (48%. For the mass lesions, the most frequent presentations were irregular shape (50%, irregular margin (50% and heterogeneous enhancement (67%. For the non-mass-like lesions, the clumped internal enhancement pattern was the dominate feature, seen in 9/14 cases (64%. Regarding enhancement kinetic curve, 21/29 (78% lesions showed suspicious malignant type kinetics. No significant difference was found in morphology (>.05, tumor size (P = 0.21, and kinetic characteristics (=.38 between non-high grade (I+II and high-grade (III pure DCIS.

  3. Astrocytic tumour grading: a comparative study of three-dimensional pseudocontinuous arterial spin labelling, dynamic susceptibility contrast-enhanced perfusion-weighted imaging, and diffusion-weighted imaging

    Energy Technology Data Exchange (ETDEWEB)

    Xiao, Hua-Feng [302 Hospital of Chinese People' s Liberation Army, Department of Radiology, Beijing (China); Chen, Zhi-Ye; Wang, Yu-Lin; Wang, Yan; Ma, Lin [People' s Liberation Army General Hospital, Department of Radiology, Beijing (China); Lou, Xin [People' s Liberation Army General Hospital, Department of Radiology, Beijing (China); University of California, Department of Neurology, Los Angeles, CA (United States); Gui, Qiu-Ping [People' s Liberation Army General Hospital, Department of Pathology, Beijing (China); Shi, Kai-Ning; Zhou, Zhen-Yu; Zheng, Dan-Dan [General Electric Healthcare (China) Co., Ltd., Beijing; Wang, Danny J.J. [University of California, Department of Neurology, Los Angeles, CA (United States)


    We hypothesized that three-dimensional pseudocontinuous arterial spin labelling (pCASL) may have similar efficacy in astrocytic tumour grading as dynamic susceptibility contrast-enhanced perfusion-weighted imaging (DSC-PWI), and the grading accuracy may be further improved when combined with apparent diffusion coefficient (ADC) values. Forty-three patients with astrocytic tumours were studied using diffusion weighted imaging (DWI), pCASL, and DSC-PWI. Histograms of ADC and normalized tumour cerebral blood flow values (nCBF on pCASL and nrCBF on DSC-PWI) were measured and analyzed. The mean 10 % ADC value was the DWI parameter that provided the best differentiation between low-grade astrocytoma (LGA) and high-grade astrocytoma (HGA). The nCBF and nrCBF (1.810 ± 0.979 and 2.070 ± 1.048) in LGA were significantly lower than those (4.505 ± 2.270 and 5.922 ± 2.630) in HGA. For differentiation between LGA and HGA, the cutoff values of 0.764 x 10{sup -3} mm{sup 2}/s for mean 10 % ADC, 2.374 for nCBF, and 3.464 for nrCBF provided the optimal accuracy (74.4 %, 86.1 %, and 88.6 %, respectively). Combining the ADC values with nCBF or nrCBF could further improve the grading accuracy to 97.7 % or 95.3 %, respectively. pCASL is an alternative to DSC-PWI for astrocytic tumour grading. The combination of DWI and contrast-free pCASL offers a valuable choice in patients with risk factors. (orig.)

  4. Topical 5-Fluorouracil for Women With High-Grade Vaginal Intraepithelial Neoplasia. (United States)

    Fiascone, Stephen; Vitonis, Allison F; Feldman, Sarah


    To examine success rates of 5-fluorouracil, excision, and laser ablation as the initial and secondary management strategies for women with high-grade vaginal intraepithelial neoplasia. We conducted a retrospective case series of women referred to a single center for management of biopsy-proven, high-grade vaginal intraepithelial neoplasia between April 1994 and May 2016. Data including demographic characteristics, human papillomavirus risk factors, antecedent Pap cytology, concurrent or prior cervical and vulvar dysplasia, and treatment outcome including follow-up Pap cytology were recorded. All women were counseled on options of excision, laser ablation, or 5-fluorouracil, which was administered intravaginally according to a standardized regimen. Recurrence was defined as a biopsy showing any vaginal intraepithelial neoplasia diagnosis after primary treatment. Forty-seven patients were treated initially with 5-fluorouracil, 35 were treated with excision, and 22 were treated with laser ablation. Demographics were similar between groups. No recurrence was noted in 35 women treated with 5-fluorouracil (74%; 95% CI 62-87%), 20 treated with excision (57%; 95% CI 41-74%), and nine treated with laser ablation (41%; 95% CI 20-61%). Among 13 patients treated with 5-fluorouracil for recurrence, eight (62%) did not experience a second recurrence. Nine of 58 (16%) patients ever treated with 5-fluorouracil reported a side effect, most commonly irritation and dyspareunia. 5-fluorouracil was associated with a 74% success rate as the initial treatment modality for high-grade vaginal dysplasia. There is also a role for 5-fluorouracil in the management of recurrent or persistent high-grade vaginal intraepithelial neoplasia.

  5. Graded Carrier Concentration Absorber Profile for High Efficiency CIGS Solar Cells


    Antonino Parisi; Riccardo Pernice; Vincenzo Rocca; Luciano Curcio; Salvatore Stivala; Cino, Alfonso C.; Giovanni Cipriani; Vincenzo Di Dio; Giuseppe Ricco Galluzzo; Rosario Miceli; Busacca, Alessandro C.


    We demonstrate an innovative CIGS-based solar cells model with a graded doping concentration absorber profile, capable of achieving high efficiency values. In detail, we start with an in-depth discussion concerning the parametrical study of conventional CIGS solar cells structures. We have used the wxAMPS software in order to numerically simulate cell electrical behaviour. By means of simulations, we have studied the variation of relevant physical and chemical parameters—characteristic of suc...

  6. Primary undifferentiated high-grade pleomorphic sarcoma in the perihepatic space: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ki Beom; Kim, Song Hoon [Dept. of Radiology, Daegu Fatima Hospital, Daegu (Korea, Republic of)


    Undifferentiated high-grade pleomorphic sarcoma (UPS) is a pleomorphic soft tissue sarcoma derived from histiocytes capable of fibroblastic transformation. UPS affects soft tissues of the body, especially the extremities and retroperitoneum, and primary UPS in the perihepatic space is extremely rare. We report a case of primary perihepatic UPS in a 44-year-old male, who presented with fever and right upper abdominal discomfort.

  7. Radiologic and Clinical Outcomes of Surgery in High Grade Spondylolisthesis Treated with Temporary Distraction Rod (United States)

    Hootkani, Alireza; Jarahi, Lida; Rezvan, Manizheh; Moayedpour, Amir


    Background Surgical techniques used in the treatment of patients with high grade lumbar spondylolisthesis (> 50% slippage) are usually associated with a great deal of controversies. We aim to evaluate the surgical outcomes of high grade spondylolisthesis treated with an intraoperative temporary distraction rod. Methods We retrospectively studied 21 patients (14 females and 7 males), aged 50.4 ± 9.2 years, who had high grade lumbar spondylolisthesis that was treated with intraoperative temporary distraction rods, neural decompression, pedicular screw fixation, and posterolateral fusion involving one more intact upper vertebra. The mean follow-up period was 39.2 months. Radiologic and clinical outcomes were measured by slip angle, slip percentage, correction rate, Oswestry Disability Index (ODI), visual analogue scale (VAS), patient's satisfaction rate in the pre- and postoperative period. Data were analyzed by SPSS ver. 11.5. Results Analysis of the preoperative visits and final follow-up visits indicated that surgery could improve ODI, lumbar VAS, and leg VAS from 60.5% to 8.2%, from 6.7 to 2.2, and from 6.9 to 1.3, respectively. Slip angle and slip percentage were also changed from -8° to -15° and from 59.2% to 21.4%, respectively. Mean correction rate at the final follow-up visit was 64.1%. Loss of correction was insignificant and a neurologic complication occurred in one patient due to misplacement of one screw. Excellent and good levels of satisfaction were observed in 90.5% of the patients. Conclusions In the surgical treatment of refractory high grade spondylolisthesis, the use of a temporary distraction rod to reduce the slipped vertebra in combination with neural decompression, posterolateral fusion, and longer instrumentation is associated with satisfactory clinical and radiologic outcomes. PMID:25729523

  8. A dosimetric comparison of four treatment planning methods for high grade glioma

    Directory of Open Access Journals (Sweden)

    Miller Robert W


    Full Text Available Abstract Background High grade gliomas (HGG are typically treated with a combination of surgery, radiotherapy and chemotherapy. Three dimensional (3D conformal radiotherapy treatment planning is still the main stay of treatment for these patients. New treatment planning methods suggest better dose distributions and organ sparing but their clinical benefit is unclear. The purpose of the current study was to compare normal tissue sparing and tumor coverage using four different radiotherapy planning methods in patients with high grade glioma. Methods Three dimensional conformal (3D, sequential boost IMRT, integrated boost (IB IMRT and Tomotherapy (TOMO treatment plans were generated for 20 high grade glioma patients. T1 and T2 MRI abnormalities were used to define GTV and CTV with 2 and 2.5 cm margins to define PTV1 and PTV2 respectively. Results The mean dose to PTV2 but not to PTV1 was less then 95% of the prescribed dose with IB and IMRT plans. The mean doses to the optic chiasm and the ipsilateral globe were highest with 3D plans and least with IB plans. The mean dose to the contralateral globe was highest with TOMO plans. The mean of the integral dose (ID to the brain was least with the IB plan and was lower with IMRT compared to 3D plans. The TOMO plans had the least mean D10 to the normal brain but higher mean D50 and D90 compared to IB and IMRT plans. The mean D10 and D50 but not D90 were significantly lower with the IMRT plans compared to the 3D plans. Conclusion No single treatment planning method was found to be superior to all others and a personalized approach is advised for planning and treating high-grade glioma patients with radiotherapy. Integral dose did not reflect accurately the dose volume histogram (DVH of the normal brain and may not be a good indicator of delayed radiation toxicity.

  9. Proposal for the award of three contracts for the supply of high-grade helium

    CERN Document Server


    This document concerns the award of three contracts for the supply of high-grade helium. Following a market survey carried out among 27 firms in ten Member States, a call for tenders (IT-2855/LHC) was sent on 15 November 2000 to five firms in three Member States. By the closing date, CERN had received tenders from four firms in three Member States. For the reasons explained in this document, the Finance Committee is invited to agree to the negotiation of the following three contracts: - a contract with MESSER GRIESHEIM (DE), the lowest bidder, for the supply of up to 26 000 kg of high-grade helium over a period of three years for an estimated amount of 655 200 Swiss francs, not subject to revision. - a contract with BOC (GB), the second lowest bidder, for the supply of up to 26 000 kg of high-grade helium over a period of three years for an estimated amount of 493 300 US dollars (808 080 Swiss francs), not subject to revision. The rate of exchange which has been used is that stipulated in the tender. - a cont...

  10. Significant worsening sperm parameters are associated to testicular hypotrophy in patients with a high grade varicocele. (United States)

    Guzel, O; Aslan, Y; Balci, M; Tuncel, A; Unal, B; Atan, A


    To investigate the relationship between testicular volume and semen parameter sin patients with unilateral high grade left varicocele. One hundred eighty seven patients who had left high grade varicocele aged 19-to-25 years were included in this study. All patients underwent a standard evaluation, including medical history and physical examination. The percentage testicular volume difference between the right and left testicles was calculated. The patients were divided into the following three groups; Group 1 (n=72) testicular volume difference 20% Group 3 (n=41). The mean age and BMI of the patients were 21.5 years and 23.1kg/m(2), respectively (P=.596, P=.943). The semen parameters and testicular volumes of the three groups were compared. The total motile sperm count, percentage of motile sperm, percentage of normal morphology sperm were found to be lower in Group 3 (P=.011, P=.012, P=.029 respectively). The mean testicular volumes for the left and the right testis were found to be 15.2cm(3) and 17.7cm(3) (P<.001), respectively. No significant difference was found in the right testicular volumes between groups (17.4, 17.7 and 18.1cm(3), P=.573). A high grade left testicular varicocele is associated with ipsilateral testicular hypotrophy and parallel to worsened sperm parameters. Copyright © 2014 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  11. Aerobic Glycolysis as a Marker of Tumor Aggressiveness: Preliminary Data in High Grade Human Brain Tumors

    Directory of Open Access Journals (Sweden)

    Andrei G. Vlassenko


    Full Text Available Objectives. Glucose metabolism outside of oxidative phosphorylation, or aerobic glycolysis (AG, is a hallmark of active cancer cells that is not directly measured with standard 18F-fluorodeoxyglucose (FDG positron emission tomography (PET. In this study, we characterized tumor regions with elevated AG defined based on PET measurements of glucose and oxygen metabolism. Methods. Fourteen individuals with high-grade brain tumors underwent structural MR scans and PET measurements of cerebral blood flow (CBF, oxygen (CMRO2 and glucose (CMRGlu metabolism, and AG, using 15O-labeled CO, O2 and H2O, and FDG, and were compared to a normative cohort of 20 age-matched individuals. Results. Elevated AG was observed in most high-grade brain tumors and it was associated with decreased CMRO2 and CBF, but not with significant changes in CMRGlu. Elevated AG was a dramatic and early sign of tumor growth associated with decreased survival. AG changes associated with tumor growth were differentiated from the effects of nonneoplastic processes such as epileptic seizures. Conclusions. Our findings demonstrate that high-grade brain tumors exhibit elevated AG as a marker of tumor growth and aggressiveness. AG may detect areas of active tumor growth that are not evident on conventional FDG PET.

  12. Prognostic Relevance of Histomolecular Classification of Diffuse Adult High-Grade Gliomas with Necrosis. (United States)

    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


    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.

  13. Adult IDH wild-type lower-grade gliomas should be further stratified. (United States)

    Aibaidula, Abudumijit; Chan, Aden Ka-Yin; Shi, Zhifeng; Li, Yanxi; Zhang, Ruiqi; Yang, Rui; Li, Kay Ka-Wai; Chung, Nellie Yuk-Fei; Yao, Yu; Zhou, Liangfu; Wu, Jinsong; Chen, Hong; Ng, Ho-Keung


    Astrocytoma of the isocitrate dehydrogenase (IDH) wild-type gene is described as a provisional entity within the new World Health Organization (WHO) classification. Some groups believe that IDH wild-type lower-grade gliomas, when interrogated for other biomarkers, will mostly turn out to be glioblastoma. We hypothesize that not all IDH wild-type lower-grade gliomas have very poor outcomes and the group could be substratified prognostically. Seven hundred and eighteen adult WHO grades II and III patients with gliomas from our hospitals were re-reviewed and tested for IDH1/2 mutations. One hundred and sixty-six patients with IDH wild-type cases were identified for further studies, and EGFR and MYB amplifications, mutations of histone H3F3A, TERT promoter (TERTp), and BRAF were examined. EGFR amplification, BRAF, and H3F3A mutations were observed in 13.8%, 6.9%, and 9.5% of patients, respectively, in a mutually exclusive pattern in IDH wild-type lower-grade gliomas. TERTp mutations were detected in 26.8% of cases. Favorable outcome was observed in patients with young age, oligodendroglial phenotype, and grade II histology. Independent adverse prognostic values of older age, nontotal resection, grade III histology, EGFR amplification, and H3F3A mutation were confirmed by multivariable analysis. Tumors were further classified into "molecularly" high grade (harboring EGFR, H3F3A, or TERTp) (median overall survival = 1.23 y) and lower grade (lacking all of the 3) (median overall survival = 7.63 y) with independent prognostic relevance. The most favorable survival was noted in molecularly lower-grade gliomas with MYB amplification. Adult IDH wild-type lower-grade gliomas are prognostically heterogeneous and do not have uniformly poor prognosis. Clinical information and additional markers, including MYB, EGFR, TERTp, and H3F3A, should be examined to delineate discrete favorable and unfavorable prognostic groups.

  14. Thermomechanical response of metal-ceramic graded composites for high-temperature aerospace applications (United States)

    Deierling, Phillip Eugene

    Airframes operating in the hypersonic regime are subjected to complex structural and thermal loads. Structural loads are a result of aggressive high G maneuvers, rapid vehicle acceleration and deceleration, and dynamic pressure, while thermal loads are a result of aerodynamic heating. For such airframes, structural members are typically constructed from steel, titanium and nickel alloys. However, with most materials, rapid elevations in temperature lead to undesirable changes in material properties. In particular, reductions in strength and stiffness are observed, along with an increase in thermal conductivity, specific heat and thermal expansion. Thus, hypersonic airframes are typically designed with external insulation, active cooling or a thermal protection system (TPS) added to the structure to protect the underling material from the effects of temperature. Such thermal protection may consist of adhesively bonded, pinned, and bolted thermal protection layers over exterior panels. These types of attachments create abrupt changes in thermal expansion and stiffness that make the structure susceptible to cracking and debonding as well as adding mass to the airframe. One of the promising materials concepts for extreme environments that was introduced in the past is the so-called Spatially Tailored Advanced Thermal Structures (STATS). The concept of STATS is rooted in functionally graded materials (FGMs), in which a directional variation of material properties exists. These materials are essentially composites and consist of two or more phases of distinct materials in which the volume fractions of each phase continuously change in space. Here, the graded material will serve a dual-purpose role as both the structural/skin member and thermal management with the goal of reducing the weight of the structure while maintaining structural soundness. This is achieved through the ability to tailor material properties to create a desired or enhanced thermomechanical response

  15. High-grade renal injuries are often isolated in sports-related trauma. (United States)

    Patel, Darshan P; Redshaw, Jeffrey D; Breyer, Benjamin N; Smith, Thomas G; Erickson, Bradley A; Majercik, Sarah D; Gaither, Thomas W; Craig, James R; Gardner, Scott; Presson, Angela P; Zhang, Chong; Hotaling, James M; Brant, William O; Myers, Jeremy B


    Most high-grade renal injuries (American Association for Surgery of Trauma (AAST) grades III-V) result from motor vehicle collisions associated with numerous concomitant injuries. Sports-related blunt renal injury tends to have a different mechanism, a solitary blow to the flank. We hypothesized that high-grade renal injury is often isolated in sports-related renal trauma. We identified patients with AAST grades III-V blunt renal injuries from four level 1 trauma centres across the United States between 1/2005 and 1/2014. Patients were divided into "Sport" or "Non-sport" related groups. Outcomes included rates of hypotension (systolic blood pressure 110bpm), concomitant abdominal injury, and procedural/surgical intervention between sports and non-sports related injury. 320 patients met study criteria. 18% (59) were sports-related injuries with the most common mechanisms being skiing, snowboarding and contact sports (25%, 25%, and 24%, respectively). Median age was 24 years for sports and 30 years for non-sports related renal injuries (p=0.049). Males were more commonly involved in sports related injuries (85% vs. 72%, p=0.011). Median injury severity score was lower for sports related injuries (10 vs. 27, ptrauma was more likely to be isolated without other significant injury (69% vs. 39% (ptrauma is more likely to occur in isolation without other abdominal or thoracic injuries and clinicians must have a high suspicion of renal injury with significant blows to the flank during sports activities. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Associations between circulating carotenoids, genomic instability and the risk of high-grade prostate cancer. (United States)

    Nordström, Tobias; Van Blarigan, Erin L; Ngo, Vy; Roy, Ritu; Weinberg, Vivian; Song, Xiaoling; Simko, Jeffry; Carroll, Peter R; Chan, June M; Paris, Pamela L


    Carotenoids are a class of nutrients with antioxidant properties that have been purported to protect against cancer. However, the reported associations between carotenoids and prostate cancer have been heterogeneous and lacking data on interactions with nucleotide sequence variations and genomic biomarkers. To examine the associations between carotenoid levels and the risk of high-grade prostate cancer, also considering antioxidant-related genes and tumor instability. We measured plasma levels of carotenoids and genotyped 20 single nucleotide polymorphisms (SNP) in SOD1, SOD2, SOD3, XRCC1, and OGG1 among 559 men with non-metastatic prostate cancer undergoing radical prostatectomy. We performed copy number analysis in a subset of these men (n = 67) to study tumor instability assessed as Fraction of the Genome Altered (FGA). We examined associations between carotenoids, genotypes, tumor instability and risk of high-grade prostate cancer (Gleason grade ≥ 4 + 3) using logistic and linear regression. Circulating carotenoid levels were inversely associated with the risk of high-grade prostate cancer; odds ratios (OR) and 95% confidence intervals (CI) comparing highest versus lowest quartiles were: 0.34 (95% CI: 0.18-0.66) for α-carotene, 0.31 (95% CI: 0.15-0.63) for β-carotene, 0.55 (0.28-1.08) for lycopene and 0.37 (0.18-0.75) for total carotenoids. SNPs rs25489 in XRCC1, rs699473 in SOD3 and rs1052133 in OGG1 modified these associations for α-carotene, β-carotene and lycopene, respectively (P ≤ 0.05). The proportion of men with a high degree of FGA increased with Gleason Score (P levels were associated with lower FGA (P = 0.04). Circulating carotenoids at diagnosis, particularly among men carrying specific somatic variations, were inversely associated with risk of high-grade prostate cancer. In exploratory analyses, higher lycopene level was associated with less genomic instability among men with low-grade disease which is novel and

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

    Directory of Open Access Journals (Sweden)

    C. S. Amene


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

  18. Functionally strain-graded nanoscoops for high power Li-ion battery anodes. (United States)

    Krishnan, Rahul; Lu, Toh-Ming; Koratkar, Nikhil


    Lithium-ion batteries show poor performance for high power applications involving ultrafast charging/discharging rates. Here we report a functionally strain-graded carbon-aluminum-silicon anode architecture that overcomes this drawback. It consists of an array of nanostructures each comprising an amorphous carbon nanorod with an intermediate layer of aluminum that is finally capped by a silicon nanoscoop on the very top. The gradation in strain arises from graded levels of volumetric expansion in these three materials on alloying with lithium. The introduction of aluminum as an intermediate layer enables the gradual transition of strain from carbon to silicon, thereby minimizing the mismatch at interfaces between differentially strained materials and enabling stable operation of the electrode under high-rate charge/discharge conditions. At an accelerated current density of ∼51.2 A/g (i.e., charge/discharge rate of ∼40C), the strain-graded carbon-aluminum-silicon nanoscoop anode provides average capacities of ∼412 mAh/g with a power output of ∼100 kW/kg(electrode) continuously over 100 charge/discharge cycles.

  19. Review of high thickness welding analysis using SYSWELD for a fusion grade reactor

    Energy Technology Data Exchange (ETDEWEB)

    Prakash, Ravi, E-mail:; Gangradey, Ranjana, E-mail:


    Vacuum vessel and Cryostat for a fusion grade machine are massive structures involving fabrication of chambers with high thickness, about thickness up to 60 mm or more, made of special grade steels. Such machines require accurate planning of welding as the distortions and tolerance levels are stringent. Vacuum vessel of ITER has “D” shaped profile and is toroidal double walled huge steel cage of about 6 m width and 19 m diameter, and the Cryostat of 30 m height and width. The huge vacuum chamber will be fabricated in various parts/sectors due to huge size and then welded with countless weld joints to give the final components. High thickness welding of vacuum vessel is considered to be one of the most important elements in building a reactor of fusion grade due to large ineluctable distortions of welded parts after welding process as it is not easy to correct the large deformations after the welding process and finally the corrections are very expensive. The present paper demonstrates results of welding simulation done using SYSWELD software. Simulation results are of review studies of identified welding process like MIG, MAG, NG-TIG, TIG and EBW for welding large structural D shaped vacuum vessel profile as a case study. Simulation has carried out for SS316LN in clamped as well as unclamped condition for a distortion tolerance of ±2 mm with various weld factors and the local–global approach.

  20. Stereotactic Radiosurgery for Recurrent or Unresectable Pilocytic Astrocytoma

    Energy Technology Data Exchange (ETDEWEB)

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


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

  1. Management of optic chiasmatic/hypothalamic astrocytomas in children

    Energy Technology Data Exchange (ETDEWEB)

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


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

  2. "Reverse Bohlman" technique for the treatment of high grade spondylolisthesis in an adult population. (United States)

    Macagno, Angel E; Hasan, Saqib; Jalai, Cyrus M; Worley, Nancy; de Moura, Alexandre B; Spivak, Jeffrey; Bendo, John A; Passias, Peter G


    Surgical techniques for effective high-grade spondylolisthesis (HGS) remain controversial. This study aims to evaluate radiographic/clinical outcomes in HGS patients treated using modified "Reverse Bohlman" (RB) technique. Review of consecutive HGS patients undergoing RB at a single university-center from 2006 to 2013. Clinical, surgical, radiographic parameters collected. Six patients identified: five with L5-S1 HGS with L4-L5 instability and one had an L4-5 isthmic spondylolisthesis and grade 1 L5-S1 isthmic spondylolisthesis. Two interbody graft failures and one L5-S1 pseudoarthrosis. Postoperative improvement of anterolisthesis (62.3% vs. 49.6%, p = 0.003), slip angle (10 vs. 5°, p = 0.005), and lumbar lordosis (49 vs. 57.5°, p = 0.049). RB technique for HGS recommended when addressing adjacent level instability/slip.

  3. STAR and AKR1B10 are down-regulated in high-grade endometrial cancer. (United States)

    Sinreih, Maša; Štupar, Saša; Čemažar, Luka; Verdenik, Ivan; Frković Grazio, Snježana; Smrkolj, Špela; Rižner, Tea Lanišnik


    Endometrial cancer is the most frequent gynecological malignancy in the developed world. The majority of cases are estrogen dependent, and are associated with diminished protective effects of progesterone. Endometrial cancer is also related to enhanced inflammation and decreased differentiation. In our previous studies, we examined the expression of genes involved in estrogen and progesterone actions in inflammation and tumor differentiation, in tissue samples from endometrial cancer and adjacent control endometrium. The aims of the current study were to examine correlations between gene expression and several demographic characteristics, and to evaluate changes in gene expression with regard to histopathological and clinical characteristics of 51 patients. We studied correlations and differences in expression of 38 genes involved in five pathophysiological processes: (i) estrogen-stimulated proliferation; (ii) estrogen-dependent carcinogenesis; (iii) diminished biosynthesis of progesterone: (iv) enhanced formation of progesterone metabolites; and (v) increased inflammation and decreased differentiation. Spearman correlation coefficient analysis shows that expression of PAQR7 correlates with age, expression of SRD5A1, AKR1B1 and AKR1B10 correlate with body mass, while expression of SRD5A1 and AKR1B10 correlate with body mass index. When patients with endometrial cancer were stratified based on menopausal status, histological grade, myometrial invasion, lymphovascular invasion, and FIGO stage, Mann-Whitney U tests revealed significantly decreased expression of STAR (4.4-fold; adjusted p=0.009) and AKR1B10 (9-fold; adjusted p=0.003) in high grade versus low grade tumors. Lower levels of STAR might lead to decreased de-novo steroid hormone synthesis and tumor differentiation, and lower levels of AKR1B10 to diminished elimination of toxic electrophilic carbonyl compounds in high-grade endometrial cancer. These data thus reveal the potential of STAR and AKR1B10 as

  4. Radiological assessment of lumbosacral dystrophic changes in high-grade spondylolisthesis

    Energy Technology Data Exchange (ETDEWEB)

    Vialle, Raphael [Armand Trousseau Hospital, Department of Paediatric Orthopaedics, Paris Cedex 12 (France); Schmit, Pierre [Necker-Enfants Malades Hospital, Department of Paediatric Radiology, Paris (France); Dauzac, Cyril; Guigui, Pierre [Beaujon Hospital, Department of Orthopaedic Surgery, Clichy Cedex (France); Wicart, Philippe [Saint-Vincent de Paul Hospital, Department of Paediatric Orthopaedics, Paris (France); Glorion, Christophe [Necker-Enfants Malades Hospital, Department of Paediatric Orthopaedics, Paris (France)


    To analyse radiographic correlates for the clinical status of patients and the deformation reducibility of high-grade lumbosacral spondylolisthesis. We also clarify the clinical and radiographic correlates of a new parameter for S1 dystrophy, the ''S1 index''. One hundred cases of high-grade isthmic lumbosacral spondylolisthesis were reviewed. We noted the dystrophic changes in the cranial sacral endplate, and the caudal endplate of L5. The severity of the spondylolisthesis was evaluated by measuring the lumbosacral kyphosis. The clinical status and the deformation reducibility (dependent on the stiffness of the deformation) were compared with these dystrophic patterns, the sagittal slope of S1 and S2 endplates and a sacral morphological marker, the S1 index. Lumbosacral kyphosis was less severe in cases with dystrophic changes of the posterior cranial edge of S1 and/or of the posterior caudal edge of L5 but its reducibility was worse. These patients were more functionally impaired. We describe and analyse this situation as a partial lumbosacral disc failure responsible for the less severe L5 slipping. The S1 index was strongly correlated with the grade of slipping, the lumbosacral kyphosis and its reducibility. We noted the same configuration among patients with a smaller S1 index, i.e. vertical S1 and S2 vertebral bodies associated with more severe but more reducible lumbosacral kyphosis. Analysing specific criteria, we think it is possible to note progressive dystrophic changes according to the natural history of lumbosacral spondylolisthesis. We think that repeated measurements of these morphological parameters in patients diagnosed with a low-grade lumbosacral spondylolisthesis could be helpful in the early detection of evolving lumbosacral kyphosis and L5 slipping. (orig.)

  5. Patient outcomes in the operative and nonoperative management of high-grade spondylolisthesis in children. (United States)

    Lundine, Kristopher M; Lewis, Stephen J; Al-Aubaidi, Zaid; Alman, Benjamin; Howard, Andrew W


    The optimal management of high-grade spondylolisthesis in the growing child is controversial. Some authors have advocated for surgery in all cases regardless of symptoms. Surgical intervention results in a >10% risk of complications with increased risk of neurological injury associated with slip reduction maneuvers. There is a paucity of literature regarding nonoperative management in this setting. This study sought to obtain outcome measures in pediatric patients with high-grade spondylolisthesis managed either operatively or nonoperatively. Database review was performed to identify patients with a high-grade (Meyerding grade III to V) spondylolisthesis managed either operatively or nonoperatively. Retrospective radiographic and chart review was performed. Patients were then contacted by phone to obtain current quality-of-life measurements using the Scoliosis Research Society (SRS)-30 questionnaire. Fifty-three patients were identified for inclusion in the study and 49 were contacted for 92% follow-up. Twenty-four patients were treated with operative intervention, and 25 patients were initially treated nonoperatively, but 10 went on to require surgical intervention. Mean age at presentation was 12.6 years (range, 8 to 17 y) and mean age at follow-up was 20.1 years (range, 10 to 29 y). There were no outcome differences between the groups. A more kyphotic slip angle was associated with worse SRS-30 outcome scores across all groups. In the nonoperative group, the slip angle was significantly larger in patients who failed conservative treatment (34 ± 17 degrees) than in those who remained nonsurgical at final follow-up (20 ± 14 degrees). Slip angle in the operative group was 27 ± 14 degrees. In surgical patients, an older age at surgery was associated with better SRS-30 outcome scores. Nonoperative management or "watchful waiting" of the minimally symptomatic or asymptomatic child with a high-grade spondylolisthesis is safe and does not lead to significant problems

  6. Regression of Subependymal Giant Cell Astrocytoma With Rapamycin in Tuberous Sclerosis Complex (United States)

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


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

  7. Combined cytotoxic effect of UV-irradiation and TiO2 microbeads in normal urothelial cells, low-grade and high-grade urothelial cancer cells. (United States)

    Imani, Roghayeh; Veranič, Peter; Iglič, Aleš; Kreft, Mateja Erdani; Pazoki, Meysam; Hudoklin, Samo


    The differentiation of urothelial cells results in normal terminally differentiated cells or by alternative pathways in low-grade or high-grade urothelial carcinomas. Treatments with traditional surgical and chemotherapeutical approaches are still inadequate and expensive, as bladder tumours are generally highly recurrent. In such situations, alternative approaches, using irradiation of the cells and nanoparticles, are promising. The ways in which urothelial cells, at different differentiation levels, respond to UV-irradiation (photolytic treatment) or to the combination of UV-irradiation and nanoparticles (photocatalytic treatment), are unknown. Here we tested cytotoxicity of UV-irradiation on (i) normal porcine urothelial cells (NPU), (ii) human low-grade urothelial cancer cells (RT4), and (iii) human high-grade urothelial cancer cells (T24). The results have shown that 1 minute of UV-irradiation is enough to kill 90% of the cells in NPU and RT4 cultures, as determined by the live/dead viability assay. On the other hand, the majority of T24 cells survived 1 minute of UV-irradiation. Moreover, even a prolonged UV-irradiation for 30 minutes killed cells. When T24 cells were pre-supplemented with mesoporous TiO2 microbeads and then UV-irradiated, the viability of these high-grade urothelial cancer cells was reduced to cells, and that the cell's ultrastructure was heavily compromised after UV-irradiation. In conclusion, our results show major differences in the sensitivity to UV-irradiation among the urothelial cells with respect to cell differentiation. To achieve an increased cytotoxicity of urothelial cancer cells, the photocatalytic approach is recommended.

  8. NAGC Pre-K-Grade 12 Gifted Education Programming Standards: A Guide to Planning and Implementing High-Quality Services (United States)

    Johnsen, Susan K., Ed.


    The new Pre-K-Grade 12 Gifted Education Programming Standards should be part of every school district's repertoire of standards to ensure that the learning needs of advanced students are being met. "NAGC Pre-K-Grade 12 Gifted Education Programming Standards: A Guide to Planning and Implementing High-Quality Services" details six standards that…

  9. Grade Level Differences in High School Students' Conceptions of and Motives for Learning Science (United States)

    Wang, Ya-Ling; Tsai, Chin-Chung


    Students' conceptions of learning science and their relations with motive for learning may vary as the education level increases. This study aimed to compare the quantitative patterns in students' conceptions of learning science (COLS) and motives for learning science (MLS) across grade levels by adopting two survey instruments. A total of 768 high school students were surveyed in Taiwan, including 204 eighth graders, 262 tenth graders, and 302 12th graders. In the current research, memorizing, testing, and calculating and practicing were categorized as reproductive conceptions of learning science, while increase of knowledge, applying, understanding and seeing-in-a-new-way were regarded as constructivist conceptions. The results of multivariate analyses of variance (MANOVA) revealed that conceptions of learning science are more constructivist as education level increases. Both tenth graders and 12th graders endorsed understanding, seeing-in-a-new-way, and the constructivist COLS composite more strongly than the eighth graders did. In addition, the results of multigroup structural equation modeling (SEM) analysis indicated that the positive relations between testing and reproductive COLS were stronger as the grade level increased, while the negative relations between reproductive COLS and deep motive were tighter with the increase in grade level.

  10. Low-Dose-Rate Definitive Brachytherapy for High-Grade Vaginal Intraepithelial Neoplasia (United States)

    Monnier, Laurie; Dumas, Isabelle; Morice, Philippe; Pautier, Patricia; Duvillard, Pierre; Azoury, Fares; Mazeron, Renaud; Haie-Meder, Christine


    Background. Treatment of high-grade vaginal intraepithelial neoplasia (VAIN) is controversial and could include surgical excision, topical medication, brachytherapy, or other treatments. We report the results of low-dose-rate (LDR) vaginal brachytherapy for grade 3 VAIN (VAIN-3) over a 25-year period at Gustave Roussy Institute. Patients and Methods. We retrospectively reviewed the files of all patients treated at Gustave Roussy Institute for VAIN-3 since 1985. The treatment consisted of LDR brachytherapy using a personalized vaginal mold and delivered 60 Gy to 5 mm below the vaginal mucosa. All patients had at least an annual gynecological examination, including a vaginal smear. Results. Twenty-eight patients were eligible. The median follow-up was 41 months. Seven patients had a follow-up brachytherapy was 63 years (range, 38–80 years). Twenty-six patients had a history of VAIN recurring after cervical intraepithelial neoplasia and 24 had a previous hysterectomy. The median brachytherapy duration was 4.5 days. Median doses to the International Commission of Radiation Units and Measurements rectum and bladder points were 68 Gy and 45 Gy, respectively. The median prescription volume (60 Gy) was 74 cm3. Only one “in field” recurrence occurred, corresponding to a 5- and 10-year local control rate of 93% (95% confidence interval, 70%–99%). The treatment was well tolerated, with no grade 3 or 4 late toxicity and only one grade 2 digestive toxicity. No second cancers were reported. Conclusion. LDR brachytherapy is an effective and safe treatment for vaginal intraepithelial neoplasia. PMID:21262875

  11. Microstructures, textures and geothermometry of graphitic carbon in low- to high-grade mylonites (United States)

    Cao, Shuyun; Neubauer, Franz; Lv, Meixia; Li, Junyu; Dong, Yanlong


    Graphitization differs from most mineral transformations occurring during diagenesis and metamorphism in that is an irreversible process. Graphitic carbon exhibits a large range of structures and chemical compositions, ranging from amorphous-like compounds (e.g. soot, low-grade coal), through a myriad of turbostratic structures (e.g. carbonaceous materials in metamorphic rocks), to rather rare crystalline flaky graphite. Graphitic material has a number of properties and the most significant one is the structural change of the graphitic materials with increase of temperature in the fault zones as well as in very low-grade to high-grade metamorphic terrains. During metamorphic processes, organic matter is progressively transformed into graphite and the degree of maturation or graphitization of graphitic materials is a potential tool, therefore, considered as a reliable indicator of peak conditions of the metamorphic grade in metamorphic petrology. In mylonites and brittle fault zones, graphitic material is rheologically very weak, a phenomenon, which results in shear concentration along zones rich in graphitic material. The characteristics and metamorphic peak conditions of graphitic material-bearing mylonites from fault zones are studied using optical microscopy, SEM, Electron Back-Scattered Diffraction (EBSD) and Raman microspectroscopy and carbon isotopic analysis. The graphite grains are distributed parallel to the mylonitic foliation and present coarse to very fine-grained microstructures. The deformation includes dislocation glide. The deformed graphite lattice-preferred orientation by EBSD measured records presents intracrystalline slip system, which is easy in the direction of the -axes and, in fact, nearly in any direction within the basal planes. The thermometry of graphitic material by Raman spectroscopy was calibrated for the temperature range from 360 to 650 °C. These structural analyses of graphitic material in mylonitic rocks allow unraveling the

  12. Comparison of predictors for high-grade cervical intraepithelial neoplasia in women with abnormal smears. (United States)

    Szarewski, Anne; Ambroisine, Laurence; Cadman, Louise; Austin, Janet; Ho, Linda; Terry, George; Liddle, Stuart; Dina, Roberto; McCarthy, Julie; Buckley, Hilary; Bergeron, Christine; Soutter, Pat; Lyons, Deirdre; Cuzick, Jack


    The detection of high-risk human papillomavirus (HPV) DNA provides higher sensitivity but lower specificity than cytology for the identification of high-grade cervical intraepithelial neoplasia (CIN). This study compared the sensitivity and specificity of several adjunctive tests for the detection of high-grade CIN in a population referred to colposcopy because of abnormal cytology. 953 women participated in the study. Up to seven tests were carried out on a liquid PreservCyt sample: Hybrid Capture II (Digene), Amplicor (Roche), PreTect HPV-Proofer (NorChip), APTIMA HPV assay (Gen-Probe), Linear Array (Roche), Clinical-Arrays (Genomica), and CINtec p16INK4a Cytology (mtm Laboratories) immunocytochemistry. Sensitivity, specificity, and positive predictive value (PPV) were based on the worst histology seen on either the biopsy or the treatment specimen after central review. 273 (28.6%) women had high-grade disease (CIN2+) on worst histology, with 193 (20.2%) having CIN3+. For the detection of CIN2+, Hybrid Capture II had a sensitivity of 99.6%, specificity of 28.4%, and PPV of 36.1%. Amplicor had a sensitivity of 98.9%, specificity of 21.7%, and PPV of 33.5%. PreTect HPV-Proofer had a sensitivity of 73.6%, specificity of 73.1%, and PPV of 52.0%. APTIMA had a sensitivity of 95.2%, specificity of 42.2%, and PPV of 39.9%. CINtec p16INK4a Cytology had a sensitivity of 83.0%, specificity of 68.7%, and PPV of 52.3%. Linear Array had a sensitivity of 98.2%, specificity of 32.8%, and PPV of 37.7%. Clinical-Arrays had a sensitivity of 80.9%, specificity of 37.1%, and PPV of 33.0%.

  13. Advances in Tumor Screening, Imaging, and Avatar Technologies for High-Grade Serous Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Anders eOhman


    Full Text Available The majority of high-grade serous ovarian carcinoma cases are detected in advanced stages when treatment options are limited. Surgery is less effective at eradicating the disease when it is widespread, resulting in high rates of disease relapse and chemoresistance. Current screening techniques are ineffective for early tumor detection and consequently, BRCA mutations carriers, with an increased risk for developing high-grade serous ovarian cancer, elect to undergo risk-reducing surgery. While prophylactic surgery is associated with a significant reduction in the risk of cancer development, it also results in surgical menopause and significant adverse side effects. The development of efficient early-stage screening protocols and imaging technologies is critical to improving the outcome and quality of life for current patients and women at increased risk. In addition, more accurate animal models are necessary in order to provide relevant in vivo testing systems and advance our understanding of the disease origin and progression. Moreover, both genetically engineered and tumor xenograft animal models enable the preclinical testing of novel imaging techniques and molecularly targeted therapies as they become available. Recent advances in xenograft technologies have made possible the creation of avatar mice, personalized tumorgrafts, which can be used as therapy testing surrogates for individual patients prior to or during treatment. High-grade serous ovarian cancer may be an ideal candidate for use with avatar models based on key characteristics of the tumorgraft platform. This review explores multiple strategies, including novel imaging and screening technologies in both patients and animal models, aimed at detecting cancer in the early stages and improving the disease prognosis.

  14. Synthesis and Characterization of High Aluminum Zeolite X from Technical Grade Materials

    Directory of Open Access Journals (Sweden)

    Seyed Kamal Masoudian


    Full Text Available Zeolites are widely used as ion exchangers, adsorbents, separation materials and catalyst due to their well-tailored and highly-reproducible structures; therefore, the synthesis of zeolite from low grade resources can be interested. In the present work, high aluminum zeolite X was prepared from mixing technical grade sodium aluminate and sodium silicate solutions at temperatures between 70°C and 100°C. The synthesized zeolite X was characterized by SEM and X-ray methods according to ASTM standard procedures. The results showed that aging of the synthesis medium at the room temperature considerably increased the selectivity of zeolite X formation. On the other hand, high temperature of reaction mixture during crystallization formed zeolite A in the product; therefore, it decreased the purity of zeolite X. In addition, it was found that increasing H2O/Na2O and decreasing Na2O/SiO2 molar ratios in the reaction mixture resulted product with higher purity. © 2013 BCREC UNDIP. All rights reservedReceived: 7th January 2013; Revised: 7th April 2013; Accepted: 19th April 2013[How to Cite: Masoudian, S. K., Sadighi, S., Abbasi, A. (2013. Synthesis and Characterization of High Alu-minum Zeolite X from Technical Grade Materials. Bulletin of Chemical Reaction Engineering & Catalysis, 8 (1: 54-60. (doi:10.9767/bcrec.8.1.4321.54-60][Permalink/DOI:] | View in  |

  15. Comparison of T2 and FLAIR imaging for target delineation in high grade gliomas

    Directory of Open Access Journals (Sweden)

    Miller Robert W


    Full Text Available Abstract Background FLAIR and T2 weighted MRIs are used based on institutional preference to delineate high grade gliomas and surrounding edema for radiation treatment planning. Although these sequences have inherent physical differences there is limited data on the clinical and dosimetric impact of using either or both sequences. Methods 40 patients with high grade gliomas consecutively treated between 2002 and 2008 of which 32 had pretreatment MRIs with T1, T2 and FLAIR available for review were selected for this study. These MRIs were fused with the treatment planning CT. Normal structures, clinical tumor volume (CTV and planning tumor volume (PTV were then defined on the T2 and FLAIR sequences. A Venn diagram analysis was performed for each pair of tumor volumes as well as a fractional component analysis to assess the contribution of each sequence to the union volume. For each patient the tumor volumes were compared in terms of total volume in cubic centimeters as well as anatomic location using a discordance index. The overlap of the tumor volumes with critical structures was calculated as a measure of predicted toxicity. For patients with MRI documented failures, the tumor volumes obtained using the different sequences were compared with the recurrent gross tumor volume (rGTV. Results The FLAIR CTVs and PTVs were significantly larger than the T2 CTVs and PTVs (p Conclusions Although both T2 and FLAIR MRI sequences are used to define high grade glial neoplasm and surrounding edema, our results show that the volumes generated using these techniques are different and not interchangeable. These differences have bearing on the use of intensity modulated radiation therapy (IMRT and highly conformal treatment as well as on future clinical trials where the bias of using one technique over the other may influence the study outcome.

  16. Greater percent-free testosterone is associated with high-grade prostate cancer in men undergoing prostate biopsy. (United States)

    Albisinni, Simone; De Nunzio, Cosimo; Tubaro, Andrea; Barry, William T; Banez, Lionel L; Freedland, Stephen J


    To analyze the serum androgen concentrations in men who underwent an initial prostate biopsy, focusing on the percent-free testosterone (%FT) as a predictor of low- and high-grade prostate cancer (PCa). Most studies have suggested that the absolute serum testosterone and free testosterone levels are not related to PCa risk. However, to date, the concurrent effect of free and total testosterone levels has not been evaluated. In particular, the association of the %FT (free testosterone/total testosterone) with PCa risk has not been explored. From 2006 to 2010, we collected data on 812 white Italian men with no history of PCa who underwent 12-core biopsy. The testosterone, free testosterone, and %FT (free testosterone/total testosterone) were examined as predictors of low-grade (Gleason score of ≤ 6) and high-grade (Gleason score ≥ 7) PCa using crude and adjusted multinomial logistic regression analysis. On multivariate analysis, testosterone (P ≥ .11) and free testosterone (P ≥ .45) were not significantly associated with low- or high-grade PCa. A greater %FT level significantly predicted high-grade PCa on both crude (P = .01) and multivariate (P = .02) analysis but not low-grade PCa (P ≥ .38). When examined in tertiles, men in the greatest %FT tertile had a significant twofold increased risk of high-grade PCa (odds ratio 2.04, 95% confidence interval 1.23-3.37, P = .005). In white Italian men, a greater %FT level was associated with an increased risk of high-grade PCa on initial prostate biopsy. These findings suggest that a high %FT level, rather than the absolute androgen levels, might be associated with high-grade PCa. Additional studies are needed to confirm our findings. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. High temperature deformation behavior, thermal stability and irradiation performance in Grade 92 steel (United States)

    Alsagabi, Sultan

    The 9Cr-2W ferritic-martensitic steel (i.e. Grade 92 steel) possesses excellent mechanical and thermophysical properties; therefore, it has been considered to suit more challenging applications where high temperature strength and creep-rupture properties are required. The high temperature deformation mechanism was investigated through a set of tensile testing at elevated temperatures. Hence, the threshold stress concept was applied to elucidate the operating high temperature deformation mechanism. It was identified as the high temperature climb of edge dislocations due to the particle-dislocation interactions and the appropriate constitutive equation was developed. In addition, the microstructural evolution at room and elevated temperatures was investigated. For instance, the microstructural evolution under loading was more pronounced and carbide precipitation showed more coarsening tendency. The growth of these carbide precipitates, by removing W and Mo from matrix, significantly deteriorates the solid solution strengthening. The MX type carbonitrides exhibited better coarsening resistance. To better understand the thermal microstructural stability, long tempering schedules up to 1000 hours was conducted at 560, 660 and 760°C after normalizing the steel. Still, the coarsening rate of M23C 6 carbides was higher than the MX-type particles. Moreover, the Laves phase particles were detected after tempering the steel for long periods before they dissolve back into the matrix at high temperature (i.e. 720°C). The influence of the tempering temperature and time was studied for Grade 92 steel via Hollomon-Jaffe parameter. Finally, the irradiation performance of Grade 92 steel was evaluated to examine the feasibility of its eventual reactor use. To that end, Grade 92 steel was irradiated with iron (Fe2+) ions to 10, 50 and 100 dpa at 30 and 500°C. Overall, the irradiated samples showed some irradiation-induced hardening which was more noticeable at 30°C. Additionally

  18. Functional assessment of high-grade ICA stenosis with duplex ultrasound and transcranial Doppler. (United States)

    Zachrisson, Helene; Fouladiun, Marita; Blomstrand, Christian; Holm, Jan; Volkmann, Reinhard


    Duplex ultrasound (DUS) has shown a >90% accuracy compared to angiography, concerning the degree of internal carotid artery (ICA) stenosis. However, uncertainty may occur in a severe stenosis, in which peak systolic velocity (PSV) may decrease owing to high flow resistance or high backward pressure. We investigated intracranial collateral flows using transcranial Doppler (TCD) to further evaluate the hemodynamic significance of high-grade ICA stenosis. In this retrospective study, 320 consecutive symptomatic patients were examined. The degree of ICA stenosis and collateral capacity in the circle of Willis was investigated by DUS and TCD. In addition, magnetic resonance angiography (MRA) was added in a subgroup of 204 patients. The criterion for hemodynamic significant ICA stenosis was established collateral flow. In 91% of all symptomatic vessels (291 vessels), an ICA stenosis of ≥70% was found. Established collateral flow always indicated precerebral carotid artery disease of ≥70%. Furthermore, in 11% of the whole study material, collateral reserve capacity was found despite high-grade (≥70%) ICA stenosis. PSV in ICA ICA stenosis is of hemodynamic significance and to assess collateral patterns. Established collateral blood flow will help to identify patients with ≥70% (ECST) carotid artery disease. TCD might be of value when flow velocity criteria combined with plaque assessment by DUS are inclusive. Other diagnostic methods may also be considered. © 2012 The Authors. Clinical Physiology and Functional Imaging © 2012 Scandinavian Society of Clinical Physiology and Nuclear Medicine.

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


    Acoustic Schwannoma; Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Meningioma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Choroid Plexus Tumor; Adult Craniopharyngioma; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade I Meningioma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Subependymal Giant Cell Astrocytoma; Adult Subependymoma; Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Childhood Supratentorial Ependymoma; Meningeal Melanocytoma; Newly Diagnosed Childhood Ependymoma; Recurrent Adult Brain Tumor; Recurrent Childhood Anaplastic Astrocytoma; Recurrent Childhood Anaplastic Oligoastrocytoma; Recurrent Childhood Anaplastic Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Diffuse Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Fibrillary Astrocytoma; Recurrent Childhood Gemistocytic Astrocytoma; Recurrent Childhood Giant Cell Glioblastoma; Recurrent Childhood Glioblastoma; Recurrent Childhood Gliomatosis Cerebri; Recurrent Childhood Gliosarcoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood

  20. Classification of high-grade spondylolistheses based on pelvic version and spine balance: possible rationale for reduction. (United States)

    Hresko, Michael T; Labelle, Hubert; Roussouly, Pierre; Berthonnaud, Eric


    Retrospective review of a radiographic database of high-grade spondylolisthesis patients in comparison with asymptomatic controls. To analyze the sagittal spinopelvic alignment in high-grade spondylolisthesis patients and identify subgroups that may require reduction to restore sagittal balance. High-grade spondylolisthesis is associated with an abnormally high pelvic incidence (PI); however, the spatial orientation of the pelvis, determined by sacral slope (SS) and pelvic tilt (PT), is not known. We hypothesized that sagittal spinal alignment would vary with the pelvic orientation. Digitized sagittal radiographs of 133 high-grade spondylolisthesis patients (mean age, 17 years) were measured to determined sagittal alignment. K-means cluster analysis identified 2 groups based on the PT and SS, which were compared by paired t test. Comparisons were made to asymptomatic controls matched for PI. High-grade spondylolisthesis patients had a mean PI of 78.9 degrees +/- 12.1 degrees . Cluster analysis identified a retroverted, unbalanced pelvis group with high PT (36.5 degrees +/- 8.0 degrees )/low SS (40.3 degrees +/- 9.0 degrees ) and a balanced pelvic group with low PT (mean 21.3 degrees +/- 8.2 degrees )/high SS (59.9 degrees +/- 11.2 degrees ). The retroverted pelvis group had significantly greater L5 incidence and lumbosacral angle with less thoracic kyphosis than the balanced pelvic group. A total of 83% of controls had a "balanced pelvis" based on the categorization by SS and PT. Analysis of sagittal alignment of high-grade spondylolisthesis patients revealed distinct groups termed "balanced" and "unbalanced" pelvis. The PT and SS were similar in controls and balanced pelvis patients. Unbalanced pelvis patients had a sagittal spinal alignment that differed from the balanced pelvis and control groups. Treatment strategies for high-grade spondylolisthesis should reflect the different mechanical strain on the spinopelvic junction in each group; reduction techniques

  1. p53 immunohistochemistry in high-grade urothelial carcinoma of the bladder is prognostically significant. (United States)

    Hodgson, Anjelica; Xu, Bin; Downes, Michelle R


    TP53 mutations are characteristic of the high-grade pathway in the dual pathway of urothelial carcinogenesis. These mutations have been correlated with aberrant accumulation of p53 protein; however the definition and significance of this vary in the literature. The aim of this study was to assess p53 immunostaining in a cohort of high-grade urothelial carcinomas by using standard published cut-offs and a novel binarized method that included assessment of the null phenotype. Each scoring method was correlated with oncological outcome. A triplicate core tissue microarray was constructed from 207 cases of high-grade urothelial carcinoma treated by cystectomy, and was stained with p53. The percentage nuclear staining was recorded for each core and averaged for every case (206 cases were evaluable). Cases were categorized as positive/negative according to published cut-offs (10%, 40%) or by binarizing them as abnormal (null phenotype or >50% positivity) and wild type (1-49% positivity). Correlation with disease-specific survival was not significant according to standard definitions of p53 positivity. When a 40% cut-off was used, a correlation with relapse-free survival was significant on univariate analysis (P = 0.038) but not on multivariate analysis (P = 0.079). Abnormal p53 expression showed a near-significant trend for association with disease-specific survival (P = 0.052) and was a significant predictor for relapse-free survival on both univariate analysis (P = 0.047) and multivariate analysis (P = 0.035). Prior to this study, the p53 null phenotype was not well described in urothelial carcinoma of the bladder. Abnormal p53 immunoexpression (null staining pattern or staining in >50% of cells) is prognostic in terms of oncological outcome. © 2017 John Wiley & Sons Ltd.

  2. Role of combined circumareolar skin excision and liposuction in management of high grade gynaecomastia

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    Arindam Sarkar


    Full Text Available Introduction: High-grade gynaecomastia (Simon IIb and III has tissue excess (skin excess, enlarged areola, and displaced nipple, which is best managed surgically; however, results of conventional breast reduction surgeries and liposuction is not very good. Aim of our study was to describe a combined technique to manage these problems to produce a good result. Material and Method: This was a 2-year study among 12 patients of high grade gynaecomastia. Clinical and laboratory findings were normal. Pre-operatively in standing position, diameter of breast and areola, position of nipple, and amount of skin excess were marked. Under general anaesthesia, tumescent infiltration, circumareolar de-epithelisation of skin excess, and liposuction was completed. Redundant portion of the breast was sharply dissected and pulled out. Areola was fixed over pectoralis fascia at mid humerus level, just medial to the mid-clavicular line. Outer borders of the de-epithelised area were apposed by the purse-string effect of a subdermal suture, and further apposed by few half buried horizontal mattress sutures. Drains for 24 hour and compressive dressings for 6 weeks were used. Result: Mean age of presentation was 25.8 year; emotional discomfort was the chief complaint. Among 12 patients, 10 patients had bilateral gynaecomastia and 8 patients had enlarged and displaced nipple-areola complex. Average hospital stay was 2.41 days and recoveries were usually uneventful. Conclusion: The problem of tissue excess and tissue displacement in high grade gynaecomastia can be well managed by this combined circumareolar skin reduction and liposuction technique to achieve a scar-less flat male chest.

  3. High-grade spondylolisthesis treated using a modified Bohlman technique: results among multiple surgeons. (United States)

    Hart, Robert A; Domes, Christopher M; Goodwin, Brady; D'Amato, Charles R; Yoo, Jung U; Turker, Ronald J; Halsey, Matthew F


    The ideal surgical management of high-grade spondylolisthesis remains unclear. Concerns regarding the original Bohlman transsacral interbody fusion technique with stand-alone autologous fibular strut include late graft fracture and incomplete reduction of lumbosacral kyphosis. The authors' goal was to evaluate the radiographic and surgical outcomes of patients treated for high-grade spondylolisthesis with either transsacral S-1 screws or standard pedicle screw fixation augmenting the Bohlman posterior transsacral interbody fusion technique. A retrospective review of patients who underwent fusion for high-grade spondylolisthesis in which a Bohlman oblique posterior interbody fusion augmented with either transsacral or standard pedicle screw fixation was performed by 4 spine surgeons was completed. Estimated blood loss, operating time, perioperative complications, and need for revision surgery were evaluated. Upright pre- and postsurgical lumbar spine radiographs were compared for slip percent and slip angle. Sixteen patients (12 female and 4 male) with an average age of 29 years (range 9-66 years) were evaluated. The average clinical follow-up was 78 months (range 5-137 months) and the average radiographic follow-up was 48 months (range 5-108 months). Ten L4-S1 and 6 L5-S1 fusions were performed. Five fibular struts and 11 titanium mesh cages were used for interbody fusion. Six patients had isolated transsacral screws placed, with 2 (33%) of the 6 requiring revision surgery for nonunion. No nonunions were observed in patients undergoing spanning pedicle screw fixation augmenting the interbody graft. Six patients experienced perioperative complications including 3 iliac crest site infections, 1 L-5 radiculopathy without motor involvement, 1 deep vein thrombosis, and 1 epidural hematoma requiring irrigation and debridement. The average estimated blood loss and operating times were 763 ml and 360 minutes, respectively. Slip percent improved from an average of 62% to 37

  4. Prevalence of concomitant intraarticular lesions in patients treated operatively for high-grade acromioclavicular joint separations. (United States)

    Pauly, Stephan; Gerhardt, Christian; Haas, Norbert P; Scheibel, Markus


    The purpose of this study is to investigate the prevalence of concomitant intraarticular lesions to the glenohumeral joint or to surrounding soft tissue structures with non-randomized prospective case series. High-grade acromioclavicular (AC) joint dislocations result from direct or indirect force impact to the shoulder girdle. Fourty consecutive patients (2 female, 38 male) with high-grade acromioclavicular joint dislocations (Rockwood III: n = 3; IV: n = 3; V: n = 34) who underwent diagnostic arthroscopy at the time of acromioclavicular joint repair were evaluated. Associated pathologic lesions were documented and treated by an all-arthroscopic approach. As a result, traumatic intraarticular lesions were found in 15% (n = 6/40) of cases. Two patients had an isolated partial tear of the subscapularis tendon. One patient had a combined tear of the subscapularis and supraspinatus tendon (PASTA type lesion). Two patients showed a type II SLAP-lesion and one patient had a type VI SLAP-lesion. Arthroscopic treatment included rotator cuff reconstruction in two cases and debridement of the partially torn tendon in one case. Two patients underwent an arthroscopic SLAP-repair and in one patient a debridement of a labral flap tear was performed. Acromioclavicular joint reconstruction was achieved via an open technique using suture anchors in 14 cases and via an all-arthroscopic approach using a double Tight-rope technique in 26 cases. To conclude, in number of cases, high-grade AC-separations may be associated with traumatic concomitant glenohumeral pathologies resulting from the same trauma impact to the shoulder girdle. A combined or an all-arthroscopic approach allows to accurately diagnose and treat associated intraarticular pathologies.

  5. Diffusion kurtosis imaging of gliomas grades II and III - a study of perilesional tumor infiltration, tumor grades and subtypes at clinical presentation

    Directory of Open Access Journals (Sweden)

    Delgado Anna F.


    Full Text Available Diffusion kurtosis imaging (DKI allows for assessment of diffusion influenced by microcellular structures. We analyzed DKI in suspected low-grade gliomas prior to histopathological diagnosis. The aim was to investigate if diffusion parameters in the perilesional normal-appearing white matter (NAWM differed from contralesional white matter, and to investigate differences between glioma malignancy grades II and III and glioma subtypes (astrocytomas and oligodendrogliomas.

  6. Synthesis of Zeolite NaA from Low Grade (High Impurities) Indonesian Natural Zeolite


    Mustain, Asalil; Wibawa, Gede; Nais, Mukhammad Furoiddun; Falah, Miftakhul


    The zeolite NaA has been successfully synthesized from the low grade natural zeolite with high impurities. The synthesis method was started by mixing natural zeolite powder with NH4Cl aqueous solution in the reactor as pretreatment. The use of pretreatment was to reduce the impurities contents in the zeolite. The process was followed by alkaline fusion hydrothermal treatment to modify the framework structure of natural zeolite and reduce the SiO2/Al2O3 ratio. Finally, the synthesized zeolite ...

  7. Primary amyloidosis with high grade transitional cell carcinoma of bladder: A rare case report

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    Prashant Gupta


    Full Text Available Primary amyloidosis of bladder is a rare disease that closely resembles bladder cancer on clinical presentation with painless gross hematuria. Pathologically this is a totally benign non-neoplastic lesion and its association with urothelial carcinoma of the bladder is rare. We herein report a 64-year-old diabetic male who has been treated for primary amyloidosis of bladder for the last 26 years presented recently with high-grade solid urothelial cancer with osseous metaplasia and sarcomatoid change of bladder with area of amyloid deposition.

  8. Wellens' syndrome can indicate high-grade LAD stenosis in case of left bundle branch block. (United States)

    Grautoff, Steffen


    Diagnosing acute myocardial infarction (AMI) in left bundle branch block (LBBB) is challenging. Modified Sgarbossa criteria are known to help detect AMI in LBBB. This is a report about an electrocardiogram (ECG) with Wellens' signs in combination with a pre-existing LBBB. The ECG of a patient with fluctuating chest pain showed very subtle and one day later more obvious Wellens'signs. A left anterior descending artery (LAD) stenosis was diagnosed and successfully treated. Wellens' syndrome can be diagnosed in a case of LBBB and help detect a high-grade LAD stenosis even if modified Sgarbossa criteria are not met.

  9. Removing boron from metallurgical grade silicon by a high basic slag refining technique


    Wu J.J.; Xu M.; Liu K.B.; Ma W.H.; Yang B.; Dai Y.N.


    A new purification method of removing boron from metallurgical grade silicon (MG-Si) using a high baisicity slag was developed in this paper. The typical impurities Al, Ca, Ti, B, P etc in MG-Si can be removed by the binary calcium sillicate slag and it is especially efficient for removing impurity Boron. It was found that the maximal distribution coefficient of boron between calcium sillicate slag and silicon reaches to 1.57 when the mass ratio of CaO/SiO2 ...

  10. Diagnostic Values of DCE-MRI and DSC-MRI for Differentiation Between High-grade and Low-grade Gliomas: A Comprehensive Meta-analysis. (United States)

    Liang, Jianye; Liu, Dexiang; Gao, Peng; Zhang, Dong; Chen, Hanwei; Shi, Changzheng; Luo, Liangping


    This study aimed to collect the studies on the role of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and dynamic susceptibility contrast MRI (DSC-MRI) in differentiating the grades of gliomas, and evaluate the diagnostic performances of relevant quantitative parameters in glioma grading. We systematically searched studies on the diagnosis of gliomas with DCE-MRI or DSC-MRI in Medline, PubMed, China National Knowledge Infrastructure database, Cochrane Library, and Embase published between January 2005 and December 2016. Standardized mean differences and 95% confidence intervals were calculated for volume transfer coefficient (K trans ), volume fraction of extravascular extracellular space (V e ), rate constant of backflux (K ep ), relative cerebral blood volume (rCBV), and relative cerebral blood flow (rCBF) using Review Manager 5.2 software. Sensitivity, specificity, area under the curve (AUC), and Begg test were calculated by Stata 12.0. Twenty-two studies with available outcome data were included in the analysis. The standardized mean difference of K trans values between high-grade glioma and low-grade glioma were 1.18 (0.91, 1.45); V e values were 1.43 (1.06, 1.80); K ep values were 0.65 (-0.05, 1.36); rCBV values were 1.44 (1.08, 1.81); and rCBF values were 1.17 (0.68, 1.67), respectively. The results were all significant statistically (P values (P = .07), and high-grade glioma had higher K trans , V e , rCBV, and rCBF values than low-grade glioma. AUC values of K trans , V e , rCBV, and rCBF were 0.90, 0.88, 0.93, and 0.73, respectively; rCBV had the largest AUC among the four parameters (P < .05). Both DCE-MRI and DSC-MRI are reliable techniques in differentiating the grades of gliomas, and rCBV was found to be the most sensitive one. Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

  11. The diagnostic value of high-frequency power-based diffusion-weighted imaging in prediction of neuroepithelial tumour grading. (United States)

    Chen, Zhiye; Zhou, Peng; Lv, Bin; Liu, Mengqi; Wang, Yan; Wang, Yulin; Lou, Xin; Gui, Qiuping; He, Huiguang; Ma, Lin


    To retrospectively evaluate the diagnostic value of high-frequency power (HFP) compared with the minimum apparent diffusion coefficient (MinADC) in the prediction of neuroepithelial tumour grading. Diffusion-weighted imaging (DWI) data were acquired on 115 patients by a 3.0-T MRI system, which included b0 images and b1000 images over the whole brain in each patient. The HFP values and MinADC values were calculated by an in-house script written on the MATLAB platform. There was a significant difference among each group excluding grade I (G1) vs. grade II (G2) (P = 0.309) for HFP and among each group for MinADC. ROC analysis showed a higher discriminative accuracy between low-grade glioma (LGG) and high-grade glioma (HGG) for HFP with area under the curve (AUC) value 1 compared with that for MinADC with AUC 0.83 ± 0.04 and also demonstrated a higher discriminative ability among the G1-grade IV (G4) group for HFP compared with that for MinADC except G1 vs. G2. HFP could provide a simple and effective optimal tool for the prediction of neuroepithelial tumour grading based on diffusion-weighted images in routine clinical practice. • HFP shows positive correlation with neuroepithelial tumour grading. • HFP presents a good diagnostic efficacy for LGG and HGG. • HFP is helpful in the selection of brain tumour boundary.

  12. A Needs Analysis Approach to the Evaluation of Iranian Third-Grade High School English Textbook

    Directory of Open Access Journals (Sweden)

    Nasser Rashidi


    Full Text Available Needs analysis as an integral part of evaluative review of English materials, mainly textbooks, requires giving sufficient attention in all English language learning contexts. This issue seems to be more demanding in English as a Foreign Language (EFL contexts where the textbooks are the main sources of input for the learners. However, in some cases, this important factor is excluded entirely or at least limited to the ideas of major stakeholders. This article reports on the findings of a study conducted to evaluate an English textbook (the third-grade high school English book, which is being used in all state high schools in Iran by using a needs analysis framework. First, the needs analysis questionnaires were administered among 180 third-grade female high school students for whom the textbook was designed. Having investigated the students’ perceived foreign language needs, the researcher then used it as the basis for evaluating the textbook. The results of the textbook evaluation revealed that although all language skills and components were almost important for the majority of the students, the textbook could not fully support all of them together. Finally, it was suggested that the textbook be revised or at least supplemented by other instructional materials, so that it could be more effective for the aforementioned learners.

  13. Dating of zircon from high-grade rocks: Which is the most reliable method?

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    Alfred Kröner


    Full Text Available Magmatic zircon in high-grade metamorphic rocks is often characterized by complex textures as revealed by cathodoluminenscence (CL that result from multiple episodes of recrystallization, overgrowth, Pb-loss and modifications through fluid-induced disturbances of the crystal structure and the original U-Th-Pb isotopic systematics. Many of these features can be recognized in 2-dimensional CL images, and isotopic analysis of such domains using a high resolution ion-microprobe with only shallow penetration of the zircon surface may be able to reconstruct much of the magmatic and complex post-magmatic history of such grains. In particular it is generally possible to find original magmatic domains yielding concordant ages. In contrast, destructive techniques such as LA-ICP-MS consume a large volume, leave a deep crater in the target grain, and often sample heterogeneous domains that are not visible and thus often yield discordant results which are difficult to interpret. We provide examples of complex magmatic zircon from a southern Indian granulite terrane where SHRIMP II and LA-ICP-MS analyses are compared. The SHRIMP data are shown to be more precise and reliable, and we caution against the use of LA-ICP-MS in deciphering the chronology of complex zircons from high-grade terranes.

  14. Nonlinear ghost waves accelerate the progression of high-grade brain tumors (United States)

    Pardo, Rosa; Martínez-González, Alicia; Pérez-García, Víctor M.


    We study a reduced continuous model describing the evolution of high grade gliomas in response to hypoxic events through the interplay of different cellular phenotypes. We show that hypoxic events, even when sporadic and/or limited in space, may have a crucial role on the acceleration of high grade gliomas growth. Our modeling approach is based on two cellular phenotypes. One of them is more migratory and a second one is more proliferative. Transitions between both phenotypes are driven by the local oxygen values, assumed in this simple model to be uniform. Surprisingly, even very localized in time hypoxia events leading to transient migratory populations have the potential to accelerate the tumor's invasion speed up to speeds close to those of the migratory phenotype. The high invasion speed persists for times much longer than the lifetime of the hypoxic event. Moreover, the phenomenon is observed both when the migratory cells form a persistent wave of cells located on the invasion front and when they form a evanescent "ghost" wave disappearing after a short time by decay to the more proliferative phenotype. Our findings are obtained through numerical simulations of the model equations both in 1D and higher dimensional scenarios. We also provide a deeper mathematical analysis of some aspects of the problem such as the conditions for the existence of persistent waves of cells with a more migratory phenotype.

  15. [Presence of high risk human papilomaviruses (HPV) in the low grade cervical lesion]. (United States)

    Iljazović, Ermina; Mustadenagić-Mujanović, Jasminka; Karasalihović, Zinaida; Cickusić, E; Avdić, S


    Low grade squamous intraepithelial lesion (LGSIL) and atypical squamous cells undetermined significance (ASCUS) are the most frequent verified cellular abnormalities. Their management are still highly controversial mostly caused by uncertainty about their histology and nature of originate. Detection of HPV DNA in the absence of cytological abnormalities can also indicate presence of high-grade cervical intraepithelial neoplasia (CIN). The aim of this study was to show the association of the benign cellular changes, ASCUS and LGSIL with oncogenic types of HPV and to prove the necessity of more intensive screening of this group of patients. Cytology and pathomorphology analyses were performed first. Identification of the presence of human papiloma virus was carried out by the Digene Hybride Capture II test for all patients. Identification of different HPV types for the particular number of patients was carried out by RFLP (Rsetriction Fragments Length of Polymorphism). Out of the 101 patients in the first group 92 (91,08%) were HPV positive, and 41, 58% had no cellular abnormalities, ASCUS or LGSIL. Out of 509 patients of the second group 26.92% were positive for HRHPV, and 78,97% of them had no cellular abnormalities, ASCUS or LGSIL. HPV 16 was detected in 27.36% (ASCUS/LGSIL) of low risk cervical lesion of the first examined period. The combination of smears with the detection of high risk HPV types increases the triage sensitivity especially at patients with mild.

  16. The relationship between MRI quantitative parameters and the expression of hypoxia inducible factor-1 alpha in cerebral astrocytoma. (United States)

    Shu, Chang; Wang, Jinhuan


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

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

    NARCIS (Netherlands)

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

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

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


    Stein, Joseph R.; Reidman, Daniel A.


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

  19. Recurrent somatic alterations of FGFR1 and NTRK2 in pilocytic astrocytoma (United States)

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


    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

  20. Pilocytic astrocytoma of the cerebellopontine angle mimicking vestibular schwannoma: report of a rare entity. (United States)

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


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

  1. [Pilocytic astrocytoma of the cerebrum presenting in an elderly patient: a case report]. (United States)

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


    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.

  2. Formation conditions of high-grade gold-silver ore of epithermal Tikhoe deposit, Russian Northeast (United States)

    Volkov, A. V.; Kolova, E. E.; Savva, N. E.; Sidorov, A. A.; Prokof'ev, V. Yu.; Ali, A. A.


    The Tikhoe epithermal deposit is located in the Okhotsk-Chukotka volcanic belt (OChVB) 250 km northeast of Magadan. Like other deposits belonging to the Ivan'insky volcanic-plutonic depression (VTD), the Tikhoe deposit is characterized by high-grade Au-Ag ore with an average Au grade of 23.13 gpt Au and Au/Ag ratio varying from 1: 1 to 1: 10. The detailed explored Tikhoe-1 orebody is accompanied by a thick (20 m) aureole of argillic alteration. Pyrite is predominant among ore minerals; galena, arsenopyrite, sphalerite, Ag sulfosalts, fahlore, electrum, and küstelite are less abundant. The ore is characterized by abundant Sebearing minerals. Cu-As geochemical specialization is noted for silver minerals. Elevated Se and Fe molar fractions of the main ore minerals are caused by their formation in the near-surface argillic alteration zone. The veins and veinlets of the Tikhoe-1 ore zone formed stepwise at a temperature of 230 to 105°C from Nachloride solution enriched in Mg and Ca cations with increasing salinity. The parameters of the ore-forming fluid correspond to those of epithermal low-sulfidation deposits and assume the formation of high-grade ore under a screening unit of volcanic rocks. In general, the composition of the ore-forming fluid fits the mineralogy and geochemistry of ore at this deposit. The similarity of the ore composition and parameters of the ore-forming fluid between the Tikhoe and Julietta deposits is noteworthy. Meanwhile, differences are mainly related to the lower temperature and fluid salinity at the Julietta deposit with respect to the Tikhoe deposit. The fluid at the Julietta deposit is depleted in most components compared with that at the Tikhoe deposit except for Sb, Cd, and Ag. The results testify to a different erosion level at the deposits as derivatives of the same ore-forming system. The large scale of the latter allows us to predict the discovery of new high-grade objects, including hidden mineralization, which is not exposed at

  3. Analysis of EZH2: micro-RNA network in low and high grade astrocytic tumors. (United States)

    Sharma, Vikas; Purkait, Suvendu; Takkar, Sonam; Malgulwar, Prit Benny; Kumar, Anupam; Pathak, Pankaj; Suri, Vaishali; Sharma, Mehar C; Suri, Ashish; Kale, Shashank Sharad; Kulshreshtha, Ritu; Sarkar, Chitra


    Enhancer of Zeste homologue2 (EZH2) is an epigenetic regulator that functions as oncogene in astrocytic tumors, however, EZH2 regulation remains little studied. In this study, we measured EZH2 levels in low (Gr-II,DA) and high grade (Gr-IV,GBM) astrocytic tumors and found significant increased EZH2 transcript level with grade(median DA-8.5, GBM-28.9).However, a different trend was reflected in protein levels, with GBMs showing high EZH2 LI(median-26.5) compared to DA (median 0.3). This difference in correlation of EZH2 protein and RNA levels suggested post-transcriptional regulation of EZH2, likely mediated by miRNAs. We selected eleven miRNAs that strongly predicted to target EZH2 and measured their expression. Three miRNAs (miR-26a-5p,miR27a-3p and miR-498) showed significant correlation with EZH2 protein, suggesting them as regulators of EZH2, however miR-26a-5p levels decreased with grade. ChIP analyses revealed H3K27me3 modifications in miR-26a promoter suggesting feedback loop between EZH2 and miR26a. We further measured six downstream miRNA targets of EZH2 and found significant downregulation of four (miR-181a/b and 200b/c) in GBM. Interestingly, EZH2 associated miRNAs were predicted to target 25 genes in glioma-pathway, suggesting their role in tumor formation or progression. Collectively, our work suggests EZH2 and its miRNA interactors may serve as promising biomarkers for progression of astrocytic tumors and may offer novel therapeutic strategies.

  4. Zircon ion microprobe dating of high-grade rocks in Sri Lanka

    Energy Technology Data Exchange (ETDEWEB)

    Kroener, A.; Williams, I.S.; Compston, W.; Baur, N.; Vitanage, P.W.; Perera, L.R.K.


    The high-grade gneisses of Sri Lanka display spectacular in-situ granulitization phenomena similar to those observed in southern India and of current interest for evolutionary models of the lower continental crust. The absolute ages of these rocks are poorly constrained and so, using the SHRIMP ion microprobe, the authors have analyzed small spots on zircons from upper amphibolite to granulite grade quartzitic and pelitic metasediments. Detrital grains from a metaquartzite of the Highland Group preserve premetamorphic U-Pb ages of between 3.17 and 2.4 Ga and indicate derivation of the sediment from an unidentified Archean source terrain. The Pb-loss patterns of these zircons and the other samples suggest severe disturbance at ca 1100 Ma ago, which the authors attribute to high-grade regional metamorphism. Two pelitic gneisses contain detrital zircons with ages up to 2.04 Ga and also record an approx. = 1100 Ma event that is also apparent from metamorphic rims around old cores and new zircon growth. A granite intrusive into the Highland Group granulites records an emplacement age of 1000-1100 Ma as well as metamorphic disturbance some 550 Ma ago but also contains older, crustally derived xenocrysts. Zircons from a metaquartzite xenolith within the granitoid Vijayan Complex are not older than approx. 1100 Ma; therefore the Vijayan is neither Archean in age nor acted as basement to the Highland Group, as previously proposed. The authors suggest that the Vijayan Complex formed significantly later than the Highland Group and that the two units were brought into contact through post-1.1 Ga thrusting. Although the granulitization phenomena in India and Sri Lanka are similar, the granulite event in Sri Lanka is not Archean in age but took place in the late Proterozoic.

  5. Precursor Lesions of High-Grade Serous Ovarian Carcinoma: Morphological and Molecular Characteristics

    Directory of Open Access Journals (Sweden)

    Amy L. Gross


    Full Text Available The lack of proven screening tools for early detection and the high mortality of ovarian serous carcinoma (OSC, particularly high grade, have focused attention on identifying putative precursor lesions with distinct morphological and molecular characteristics. The finding of occult invasive and intraepithelial fallopian tube carcinomas in prophylactically removed specimens from asymptomatic high-risk BRCA 1/2-mutation carriers supports the notion of an origin for OSC in the fallopian tube. The intraepithelial carcinomas have been referred to as serous intraepithelial carcinomas (STICs but our own findings (unpublished data and recent reports have drawn attention to a spectrum of changes that fall short of STICs that we have designated serous tubal intraepithelial lesions (STILs.

  6. Structural Evolution of Nonoperatively Treated High-Grade Partial-Thickness Tears of the Supraspinatus Tendon. (United States)

    Kong, Bong Young; Cho, Minjoon; Lee, Hwa Ryeong; Choi, Young Eun; Kim, Sae Hoon


    High-grade partial-thickness rotator cuff tears (hPTRCTs) are frequently encountered in the shoulder. However, little information is available on the prevalence or timing of tear progression. Purpose/Hypothesis: The purpose was to prospectively evaluate the structural progression of hPTRCTs with a minimum follow-up of 1 year using magnetic resonance imaging (MRI). The hypothesis was that a substantial portion of hPTRCT patients would experience tear progression or evolution to a full-thickness rotator cuff tear. Case series; Level of evidence, 4. Between May 2010 and December 2015, 362 patients were diagnosed with hPTRCT (tear involvement >50% of the mediolateral length of the footprint) of the supraspinatus and were treated nonoperatively. Among these patients, 81 underwent follow-up MRI at least 1 year after initial presentation, and these patients were included in the final analysis. Initial and follow-up MRIs were used to determine whether tears had improved, had not changed, or had progressed. A change in tear involvement of >20% was defined as a significant change. Patients were categorized as follows: (1) a decrease in tear involvement of >20% (improved), (2) an increase or decrease of ≤20% (no change), or (3) an increase in tear involvement of >20% (progressed). Demographic data and morphologic data were analyzed to identify variables related to tear progression. Among them, severity of tendinosis was graded using MRIs: grade 1 (mild tendinosis), mild focal increase in tendon signal; grade 2 (moderate tendinosis), moderate focal increase in tendon signal; and grade 3 (marked tendinosis), marked generalized increase in tendon signal. At initial diagnosis, 23 were articular-side (28%) and 58 were bursal-side (72%) hPTRCTs. The study cohort was composed of 51 women and 30 men, and the mean patient age was 62.3 years (range, 41-77 years). Follow-up MRI was performed at a mean 19.9 ± 10.9 months (range, 12-52 months). A significant change in tear involvement

  7. A green preparation of Mn-based product with high purity from low-grade rhodochrosite (United States)

    Lian, F.; Ma, L.; Chenli, Z.; Mao, L.


    The low-grade rhodochrosite, the main resources for exploitation and applications in China, contains multiple elements such as iron, silicon, calcium and magnesium. So the conventional preparation of manganese sulphate and manganese oxide with high purity from electrolytic product is characterized by long production-cycle, high-resource input and high-pollution discharge. In our work, a sustainable preparation approach of high pure MnSO4 solution and Mn3O4 was studied by employing low-grade rhodochrosite (13.86%) as raw material. The repeated leaching of rhodochrosite with sulphuric acid was proposed in view of the same ion effect, in order to improve the solubility of Mn2+ and inhibit the dissolution of the impurities Ca2+ and Mg2+. With the aid of theoretical calculation, BaF2 was chosen to remove Ca2+ and Mg2+ completely in the process of purifying. The results showed that the impurities such as Ca2+, Mg2+, Na+ were decreased to less than 20ppm, and the Ni- and Fe- impurities were decreased to less than 1ppm, which meets the standards of high pure reagent for energy and electronic materials. The extraction ratio and the recovery ratio of manganese reached 94.3% and 92.7%, respectively. Moreover, the high pure Mn3O4 was one-step synthesized via the oxidation of MnSO4 solution with the ratios of OH-/Mn2+=2 and Mn2+/H2O2=1.03, and the recovery rate of manganese reaches 99%.

  8. Graded Carrier Concentration Absorber Profile for High Efficiency CIGS Solar Cells

    Directory of Open Access Journals (Sweden)

    Antonino Parisi


    Full Text Available We demonstrate an innovative CIGS-based solar cells model with a graded doping concentration absorber profile, capable of achieving high efficiency values. In detail, we start with an in-depth discussion concerning the parametrical study of conventional CIGS solar cells structures. We have used the wxAMPS software in order to numerically simulate cell electrical behaviour. By means of simulations, we have studied the variation of relevant physical and chemical parameters—characteristic of such devices—with changing energy gap and doping density of the absorber layer. Our results show that, in uniform CIGS cell, the efficiency, the open circuit voltage, and short circuit current heavily depend on CIGS band gap. Our numerical analysis highlights that the band gap value of 1.40 eV is optimal, but both the presence of Molybdenum back contact and the high carrier recombination near the junction noticeably reduce the crucial electrical parameters. For the above-mentioned reasons, we have demonstrated that the efficiency obtained by conventional CIGS cells is lower if compared to the values reached by our proposed graded carrier concentration profile structures (up to 21%.

  9. Cerebral vasomotor reactivity and apnea test in symptomatic and asymptomatic high-grade carotid stenosis

    Directory of Open Access Journals (Sweden)

    Lučić-Prokin Aleksandra


    Full Text Available Introduction. Cerebral vasomotor reactivity (VMR represents an autoregulatory response of the arterial trunks on the specific vasoactive stimuli, most commonly CO2. Objective. The aim of this retrospective study was to compare VMR in high-grade symptomatic (SCAS and asymptomatic carotid stenosis (ACAS, using the apnea test to evaluate the hemodynamic status. Methods. The study included 50 patients who were hospitalized at the neurology and vascular surgery departments as part of preparation for carotid endarterectomy. We evaluated VMR by calculating the breath holding index (BHI in 34 patients with SCAS and 16 patients with ACAS, with isolated high-grade carotid stenosis. We evaluated the impact of risk factors and collateral circulation on BHI, as well as the correlation between the degree of carotid stenosis and BHI. Results. A pathological BHI was more frequent in the SCAS group (p<0.01. There was no difference in the range of BHI values between the groups, both ipsilaterally and contralaterally. Only male gender was associated with pathological BHI in both groups (p<0.05. Collateral circulation did not exist in over 60% of all subjects. We confirmed a negative correlation between the degree of carotid stenosis and BHI. Conclusion. SCAS and ACAS patients present with different hemodynamics. While ACAS patients have stable hemodynamics, combination of hemodynamic and thromboembolic effects is characteristic of SCAS patients.

  10. Automated high-grade prostate cancer detection and ranking on whole slide images (United States)

    Huang, Chao-Hui; Racoceanu, Daniel


    Recently, digital pathology (DP) has been largely improved due to the development of computer vision and machine learning. Automated detection of high-grade prostate carcinoma (HG-PCa) is an impactful medical use-case showing the paradigm of collaboration between DP and computer science: given a field of view (FOV) from a whole slide image (WSI), the computer-aided system is able to determine the grade by classifying the FOV. Various approaches have been reported based on this approach. However, there are two reasons supporting us to conduct this work: first, there is still room for improvement in terms of detection accuracy of HG-PCa; second, a clinical practice is more complex than the operation of simple image classification. FOV ranking is also an essential step. E.g., in clinical practice, a pathologist usually evaluates a case based on a few FOVs from the given WSI. Then, makes decision based on the most severe FOV. This important ranking scenario is not yet being well discussed. In this work, we introduce an automated detection and ranking system for PCa based on Gleason pattern discrimination. Our experiments suggested that the proposed system is able to perform high-accuracy detection ( 95:57% +/- 2:1%) and excellent performance of ranking. Hence, the proposed system has a great potential to support the daily tasks in the medical routine of clinical pathology.

  11. HPV DNA genotyping test in low and high grade intraephitelial lesions

    Directory of Open Access Journals (Sweden)

    Maria Gabriella Lepore


    Full Text Available The human papillomavirus (HPV is certainly one of the few viruses associated with cancer and is present in a significant number of cancers of the anus, penis, vagina, vulva and in almost all cervical cancers.The aim of our work is to evaluate the impact of genotypes high-risk oncogenic (HR in low-grade (LSIL and high grade (HSIL intraepithelial lesions. In it are also evaluated the impact of genotypes low oncogenic risk (LR and the percentage of non-detection (NR Papillomavirus DNA Between January 2008 and June 2009 we submitted for HPV DNA genotyping test 392 patients, seronegative for HIV1/2, of which 278 with LSIL and 114 with HSIL. In 250 patients tested positive for HPV DNA HR the type 16 is present in 102 patients (41%, the 18 in 62 (25%, the 31 in 37 patients (15%, the 33 in 13 patients (5%; also was limited the simultaneous presence of 16 and 18 (13 patients 5% The search for HPV DNA is a modern method of study of cervical pathology. Optimizes the follow-up of intraepithelial lesions and the therapeutic intervention, avoiding the dangers of over/ undertreatment and allows to monitor women treated for cervical pathology.

  12. Detection of high-grade small bowel obstruction on conventional radiography with convolutional neural networks. (United States)

    Cheng, Phillip M; Tejura, Tapas K; Tran, Khoa N; Whang, Gilbert


    The purpose of this pilot study is to determine whether a deep convolutional neural network can be trained with limited image data to detect high-grade small bowel obstruction patterns on supine abdominal radiographs. Grayscale images from 3663 clinical supine abdominal radiographs were categorized into obstructive and non-obstructive categories independently by three abdominal radiologists, and the majority classification was used as ground truth; 74 images were found to be consistent with small bowel obstruction. Images were rescaled and randomized, with 2210 images constituting the training set (39 with small bowel obstruction) and 1453 images constituting the test set (35 with small bowel obstruction). Weight parameters for the final classification layer of the Inception v3 convolutional neural network, previously trained on the 2014 Large Scale Visual Recognition Challenge dataset, were retrained on the training set. After training, the neural network achieved an AUC of 0.84 on the test set (95% CI 0.78-0.89). At the maximum Youden index (sensitivity + specificity-1), the sensitivity of the system for small bowel obstruction is 83.8%, with a specificity of 68.1%. The results demonstrate that transfer learning with convolutional neural networks, even with limited training data, may be used to train a detector for high-grade small bowel obstruction gas patterns on supine radiographs.

  13. The molecular biology of WHO grade II gliomas. (United States)

    Marko, Nicholas F; Weil, Robert J


    The WHO grading scheme for glial neoplasms assigns Grade II to 5 distinct tumors of astrocytic or oligodendroglial lineage: diffuse astrocytoma, oligodendroglioma, oligoastrocytoma, pleomorphic xanthoastrocytoma, and pilomyxoid astrocytoma. Although commonly referred to collectively as among the "low-grade gliomas," these 5 tumors represent molecularly and clinically unique entities. Each is the subject of active basic research aimed at developing a more complete understanding of its molecular biology, and the pace of such research continues to accelerate. Additionally, because managing and predicting the course of these tumors has historically proven challenging, translational research regarding Grade II gliomas continues in the hopes of identifying novel molecular features that can better inform diagnostic, prognostic, and therapeutic strategies. Unfortunately, the basic and translational literature regarding the molecular biology of WHO Grade II gliomas remains nebulous. The authors' goal for this review was to present a comprehensive discussion of current knowledge regarding the molecular characteristics of these 5 WHO Grade II tumors on the chromosomal, genomic, and epigenomic levels. Additionally, they discuss the emerging evidence suggesting molecular differences between adult and pediatric Grade II gliomas. Finally, they present an overview of current strategies for using molecular data to classify low-grade gliomas into clinically relevant categories based on tumor biology.

  14. Surgical and clinical aspects of cerebellar pilomyxoid-spectrum astrocytomas in children. (United States)

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


    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.

  15. High grade prostatic intraepithelial neoplasia in military working dogs with and without prostate cancer. (United States)

    Aquilina, J W; McKinney, L; Pacelli, A; Richman, L K; Waters, D J; Thompson, I; Burghardt, W F; Bostwick, D G


    High grade prostatic intraepithelial neoplasia (PIN) is the most likely precursor of human prostate cancer and is commonly found in men undergoing prostatic needle biopsy for suspected cancer. Recent work has demonstrated that pet dogs, like humans, develop PIN spontaneously and in association with prostate cancer. Pet dogs are the most domesticated animal, sharing the habitat and oftentimes the diet of their owners. If PIN and prostate cancer are strongly related to environmental factors, then the prevalence of these findings might differ in a population of dogs such as military working dogs which is not exposed to the habitat and diet of humans. In this study, we determined the prevalence of PIN in prostates of aged military working dogs with and without prostatic adenocarcinoma. Cases were selected from the military working dog slide and tissue archive at the Armed Forces Institute of Pathology, Washington, DC. The most recent 329 necropsies (1991 to 1996) were examined histologically by multiple reviewers; of these, 199 dogs (60%) were found to have evaluable prostatic tissue. In addition, the most recent 50 necropsies (1958 to 1996) with the diagnosis of prostatic cancer were examined, of which 25 cases (50%) were found to have evaluable prostatic adenocarcinoma. In most cases, a single large transverse section of prostatic tissue was available for review. Medical records for each dog were reviewed independently, and age, clinical history, indications for euthanasia, and other health problems were recorded. High grade PIN was identified in 3% of dogs (6 of 199 dogs) without prostate cancer. A total of 50.8% of dogs in this study group (101 of 199 dogs) were known to be sexually intact, 26.7% of dogs (53 of 199 dogs) were castrated, and the status of the remaining 22.6% of dogs (45 of 199 dogs) was unknown. High grade PIN was present in 18 of 25 dogs (72%) with prostatic adenocarcinoma. Of these cases, 11 dogs (44%) were castrated, 4 dogs (16%) were intact, and

  16. Time Spent on Homework and High School Grades: A Large-Sample Path Analysis. (United States)

    Keith, Timothy Z.


    Time spent on homework was found to be important in determining student grades. Further, it was suggested that increased homework demands and more stringent grading standards might increase both student achievement and confidence in schools. (Author/AL)

  17. Teachers' Grading Decision Making (United States)

    Isnawati, Ida; Saukah, Ali


    This study investigated teachers' grading decision making, focusing on their beliefs underlying their grading decision making, their grading practices and assessment types, and factors they considered in grading decision making. Two teachers from two junior high schools applying different curriculum policies in grade reporting in Indonesian…

  18. Grading More Accurately (United States)

    Rom, Mark Carl


    Grades matter. College grading systems, however, are often ad hoc and prone to mistakes. This essay focuses on one factor that contributes to high-quality grading systems: grading accuracy (or "efficiency"). I proceed in several steps. First, I discuss the elements of "efficient" (i.e., accurate) grading. Next, I present analytical results…

  19. Finasteride Does Not Increase the Risk of High-grade Prostate Cancer: A Bias-adjusted Modeling Approach (United States)

    Redman, Mary W.; Tangen, Catherine M.; Goodman, Phyllis J.; Parnes, Howard; Ford, Leslie G.; Lucia, M. Scott; Coltman, Charles A.; Thompson, Ian M.


    The Prostate Cancer Prevention Trial found that seven years of administration of finasteride reduced the risk of prostate cancer by 25% but with an apparent increased risk of high grade disease. Subsequent analyses found that finasteride affects cancer detection and improves accuracy of tumor grading at biopsy. We herein estimate the impact of finasteride on the risk of overall and high grade prostate cancer, accounting for these biases. Study endpoints (biopsy-proven cancer or a 7-year end-of-study biopsy) were available in 10,182 of 15,990 subjects assessable for 7-year status and grading information from 500 subjects diagnosed with cancer who underwent radical prostatectomy. Prostate cancer was observed in 22.9% (4.8% with high grade) in the placebo group versus 16.6% (5.8% with high grade) in the finasteride group. In this bias-adjusted analysis, the estimated rates are 21.1% (4.2%) and 14.7% (4.8%), respectively, a 30% risk reduction in prostate cancer (RR =0.70 (95% confidence interval (CI) =0.64-0.76, pfinasteride. Incorporating the prostatectomy data, estimated rates of high grade cancers are 8.2% (placebo) versus 6.0% (finasteride), a 27% risk reduction (RR = 0.73 (95% CI=0.56-0.96, p=0.02)) with finasteride. While the observed risk of high grade disease is greater with finasteride, this appears to be through facilitated diagnosis, primarily due to increased biopsy sensitivity. Men undergoing regular prostate cancer screening or who express an interest in cancer prevention should be informed of this prevention opportunity. PMID:19138953

  20. Surgical Treatment as a Principle for Patients with High-Grade Pancreatic Neuroendocrine Carcinoma

    DEFF Research Database (Denmark)

    Haugvik, Sven-Petter; Janson, Eva Tiensuu; Österlund, Pia


    BACKGROUND: This study aimed to evaluate the role of surgery for patients with high-grade pancreatic neuroendocrine carcinoma (hgPNEC) in a large Nordic multicenter cohort study. Prior studies evaluating the role of surgery for patients with hgPNEC are limited, and the benefit of the surgery...... is uncertain. METHODS: Data from patients with a diagnosis of hgPNEC determined between 1998 and 2012 were retrospectively registered at 10 Nordic university hospitals. Kaplan-Meier curves were used to compare the overall survival of different treatment groups, and Cox-regression analysis was used to evaluate....... Patients selected for resection of the primary tumor and synchronous liver metastases had a high 3-year survival rate. Selected patients with both localized hgPNEC and metastatic hgPNEC should be considered for radical surgical treatment....

  1. Design and optimization of high reflectance graded index optical filter with quintic apodization (United States)

    Praveen Kumar, Vemuri S. R. S.; Sunita, Parinam; Kumar, Mukesh; Rao, Parinam Krishna; Kumari, Neelam; Karar, Vinod; Sharma, Amit L.


    Rugate filters are a special kind of graded-index films that may provide advantages in both, optical performance and mechanical properties of the optical coatings. In this work, design and optimization of a high reflection rugate filter having reflection peak at 540nm has been presented which has been further optimized for side-lobe suppression. A suitable number of apodization and matching layers, generated through Quintic function, were added to the basic sinusoidal refractive index profile to achieve high reflectance of around 80% in the rejection window for normal incidence. Smaller index contrast between successive layers in the present design leads to less residual stress in the thinfilm stack which enhances the adhesion and mechanical strength of the filter. The optimized results show excellent side lobe suppression achieved around the stopband.

  2. Increased variability of watershed areas in patients with high-grade carotid stenosis

    DEFF Research Database (Denmark)

    Kaczmarz, Stephan; Griese, Vanessa; Preibisch, Christine


    . Despite of high relevance for both clinical diagnostics and research, individual in vivo WSA definition is fairly limited to date. Thus, this study proposes a standardized segmentation approach to delineate individual WSAs by use of time-to-peak (TTP) maps and investigates spatial variability...... time atlas and individual super-selective arterial spin labeling. We compared spatial variability of WSA probability maps between groups and assessed TTP differences between hemispheres in individual and group-average watershed locations. Results: Patients showed significantly higher spatial...... of individual WSAs. Methods: We defined individual watershed masks based on relative TTP increases in 30 healthy elderly persons and 28 patients with unilateral, high-grade carotid stenosis, being at risk for watershed-related hemodynamic impairment. Determined WSA location was confirmed by an arterial transit...

  3. The 9th Grade Shock and the High School Dropout Crisis (United States)

    Pharris-Ciurej, Nikolas; Hirschman, Charles; Willhoft, Joseph


    Retrospective questions on educational attainment in national surveys and censuses tend to over-estimate high school graduation rates by 15 to 20 percentage points relative to administrative records. Administrative data on educational enrollment are, however, only available at the aggregate level (state, school district, and school levels) and the recording of inter-school transfers are generally incomplete. With access to linked individual-level administrative records from a very large “West Coast metropolitan school district” we track patterns of high school attrition and on-time high school graduation of individual students. Even with adjustments for the omission of out-of-district transfers (estimates of omission are presented), the results of this study show that failure in high school, as indexed by retention and attrition, are almost as common as on-time high school graduation. In addition to the usual risk factors of disadvantaged background, we find that the “9th grade shock”—an unpredicted decline in academic performance upon entering high school—is a key mechanism behind the continuing crisis of high school attrition. PMID:23017804

  4. High Thermal Conductivity Functionally Graded Heat Sinks for High Power Packaging Project (United States)

    National Aeronautics and Space Administration — This NASA SBIR Phase I program proposes the development of a high thermal conductivity (400 W/mK), low coefficient of thermal expansion (7-10 ppm/?K), and light...

  5. “Reverse Bohlman” technique for the treatment of high grade spondylolisthesis in an adult population (United States)

    Macagno, Angel E.; Hasan, Saqib; Jalai, Cyrus M.; Worley, Nancy; de Moura, Alexandre B.; Spivak, Jeffrey; Bendo, John A.; Passias, Peter G.


    Background/aims Surgical techniques for effective high-grade spondylolisthesis (HGS) remain controversial. This study aims to evaluate radiographic/clinical outcomes in HGS patients treated using modified “Reverse Bohlman” (RB) technique. Methods Review of consecutive HGS patients undergoing RB at a single university-center from 2006 to 2013. Clinical, surgical, radiographic parameters collected. Results Six patients identified: five with L5-S1 HGS with L4-L5 instability and one had an L4-5 isthmic spondylolisthesis and grade 1 L5-S1 isthmic spondylolisthesis. Two interbody graft failures and one L5-S1 pseudoarthrosis. Postoperative improvement of anterolisthesis (62.3% vs. 49.6%, p = 0.003), slip angle (10 vs. 5°, p = 0.005), and lumbar lordosis (49 vs. 57.5°, p = 0.049). Conclusions RB technique for HGS recommended when addressing adjacent level instability/slip. PMID:26955227

  6. The supporting effects of high luminous conditions on grade 3 oral reading fluency scores. (United States)

    Mott, Michael S; Robinson, Daniel H; Williams-Black, Thea H; McClelland, Susan S


    The universality of the impact of daylight is a common thread that defines humanity. Day light affects us in a variety of ways -visually, psychologically and biologically. Artificial lighting research has explored ways in which artificial lighting may substitute for daylight and enhance human health and wellbeing. Recently, a study by Mott et al. 2011 found that the usage of high intensity, yet glare free lighting, (referred to as Focus light setting) during reading instruction increased grade 3 students' oral reading fluency (ORF) scores, a key index of reading comprehension. The current study further explored the effect of Focus lighting during literacy instruction with at-risk grade 3 students (n = 172). Over the course of an academic year, the Focus lighting students increased their ORF scores at a greater rate than did the Normal lighting students. These findings, in combination with earlier lighting research, suggest that artificial lighting plays a key role in helping to create an effective learning environment to ensure children reach their full potential. More systematic research, however, is needed to understand the mechanisms by which artificial lighting may contribute to the learning environment: visually, biologically and/or psychologically.

  7. Therapeutically blocking Interleukin-11 Receptor-α enhances doxorubicin cytotoxicity in high grade type I endometrioid tumours. (United States)

    Winship, Amy; Van Sinderen, Michelle; Rainczuk, Katarzyna; Dimitriadis, Evdokia


    High grade type I endometrial cancers have poor prognosis. Interleukin (IL)11 is elevated in tumours and uterine lavage with increasing tumour grade in women. IL11 regulates cell cycle, invasion and migration and we recently demonstrated that IL11 receptor (R)α inhibition impaired low and moderate grade endometrial tumourigenesis in vivo. In this report, we hypothesized that micro-RNA(miR)-1 regulates IL11 and that IL11 promotes high grade endometrial tumour growth. We aimed to determine whether combination treatment using an anti-human IL11Rα blocking antibody (Ab) and doxorubicin chemotherapeutic impairs high grade tumour growth. MiR-1 was absent in human endometrial tumours versus human benign endometrium (n = 10/group). Transfection with miR-1 mimic restored miR-1 expression, down-regulated IL11 mRNA and impaired cell viability in grade 3-derived AN3CA human endometrial epithelial cancer cells. AN3CA cell proliferation was reduced in response to Ab and doxorubicin combination treatment versus Ab, IgG control, or doxorubicin alone. Subcutaneous xenograft tumours were established in female Balb/c athymic nude mice using AN3CA cells expressing IL11 and IL11Rα. Administration of recombinant human IL11 to mice (n = 4/group) activated IL11 downstream target, signal transducers and activators of transcription (STAT3) and significantly increased tumour growth (p < 0.05), suggesting that IL11 promotes high grade tumour growth. IL11Rα blocking Ab reduced STAT3 phosphorylation and combination treatment with doxorubicin resulted in a significant reduction in tumour growth (p < 0.05) compared to Ab, doxorubicin, or IgG control. Our data suggest that therapeutically targeting IL11Rα in combination with doxorubicin chemotherapy could inhibit high grade type I endometrioid cancer growth.

  8. High quality broadband spatial reflections of slow Rayleigh surface acoustic waves modulated by a graded grooved surface

    KAUST Repository

    Xu, Yanlong


    We report high quality broadband spatial reflections of Rayleigh surface acoustic waves (SAWs) through a graded grooved surface. High quality means that no wave is allowed to transmit and the incident wave is nearly all reflected to the input side. The graded grooved surface is structured by drilling one dimensional array of graded grooves with increased depths on a flat surface. We investigate SAW dispersion relations, wave field distribution at several typical SAW wavelengths, and time evolution of a Gaussian pulse through the graded grooved surface. Results show that the input broadband Rayleigh SAWs can be slowed, spatially enhanced and stopped, and finally reflected to the input side. The study suggests that engraving the flat surface can be used as an efficient and economical way to manipulate Rayleigh SAWs, which has potential application in novel SAW devices such as filters, reflectors, sensors, energy harvesters, and diodes.

  9. The Role of Halogens in High-Grade Metamorphism and Anatexis (United States)

    Aranovich, L.; Safonov, O.


    We review factors controlling the distribution of the two major halogens, F and Cl, in high-grade metamorphic rocks; their compositional correlations and partitioning between minerals; experimental data on stability and phase equilibria of the halogen-bearing minerals; the influence of halogens on Fe-Mg exchange reactions; and the means of estimating concentrations/activity of halogen species concentration/ activity in the fluid phase ("chlorimetry and fluorimetry") via calculation of equilibrium conditions for mineral assemblages containing halogen-bearing phases. Clear negative correlation between the F content and XFe=Fe/(Fe+Mg) suggests that natural biotite and amphibole obey the Fe-F avoidance rule. A strong positive correlation exists between K and Cl in amphibole. A scattering of points on the XFe -Cl and TiO2- Cl diagrams indicate the possible involvement of an exotic Cl-rich phase (fluid or melt) during the formation of Cl-bearing biotite and amphibole. Fluorine and Cl substituting for OH-groups substantially stabilize minerals relative to dehydration and melting. They should also strongly affect partitioning of Fe and Mg between biotite, amphibole and anhydrous minerals. This effect is quantified for Fe-Mg exchange reactions involving biotite (Zhu and Sverjensky, 1992), but remains to be evaluated for amphibole. Calculations based on recent thermodynamic systematics show that the relatively Mg-rich, Cl-poor biotite (for example, XFe = 0.4 and about 0.2 wt.% Cl) may coexist with a fairly Cl-rich fluid, i.e. total Cl/(Cl+H2O) from 0.1-0.3, depending on the assemblage, under granulite facies P-T conditions. Alkali (and Ca) metasomatism caused by interaction of high grade rocks with halogen-bearing fluids has major impact on the subsolidus phase transformations and melting processes during high-grade metamorphism and anatexis. For example, an increase in sodium content in plagioclase (Pl) by 20 mol% due to infiltration of Na- fluid into the quartz (Qtz

  10. Cigarette Smoking Trajectories From Sixth to Twelfth Grade: Associated Substance Use and High School Dropout. (United States)

    Orpinas, Pamela; Lacy, Beth; Nahapetyan, Lusine; Dube, Shanta R; Song, Xiao


    The purpose of this longitudinal study was to identify distinct trajectories of cigarette smoking from sixth to twelfth grade and to characterize these trajectories by use of other drugs and high school dropout. The diverse sample for this analysis consisted of a cohort of 611 students from Northeast Georgia who participated in the Healthy Teens Longitudinal Study (2003-2009). Students completed seven yearly assessments from sixth through twelfth grade. We used semi-parametric, group-based modeling to identify groups of students whose smoking behavior followed a similar progression over time. Current smoking (past 30 day) increased from 6.9% among sixth graders to 28.8% among twelfth graders. Four developmental trajectories of cigarette smoking were identified: Abstainers/Sporadic Users (71.5% of the sample), Late Starters (11.3%), Experimenters (9.0%), and Continuous Users (8.2%). The Abstainer/Sporadic User trajectory was composed of two distinct groups: those who never reported any tobacco use (True Abstainers) and those who reported sporadic, low-level use (Sporadic Users). The True Abstainers reported significantly less use of alcohol and other drugs and lower dropout rates than students in all other trajectories, and Sporadic Users had worse outcomes than True Abstainers. Experimenters and Continuous Users reported the highest drug use. Over one-third of Late Starters (35.8%) and almost half of Continuous Users (44.4%) dropped out of high school. Cigarette smoking was associated with behavioral and academic problems. Results support early and continuous interventions to reduce use of tobacco and other drugs and prevent high school dropout. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail:

  11. Surgery of high grade gliomas - pros in favor of maximal cytoreductive surgery

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    C. Abrudan


    Full Text Available Background: Malignant glioma is themost common primary brain tumour inadults. More and more studies are focusedon the role of surgery in prolonged medianof survival and survival at two years. Thepurpose of this study is to add somearguments in favour of radical surgery inmalignant glioma.Material and Methods: The study is based433 cases of high grade cerebral gliomaoperated between 01.01.2000-31.12.2009 atthe Department of Neurosurgery, ClujCounty Emergency Hospital. We analyzedage, gender, type and duration ofsymptoms, type of surgery, pathologicaldiagnosis and the correlation of thesefactors with overall survival. Data for longterm follow up were available for 266patients.Results: The results shows, according totheir histological features, the fallowingdispersions: astrocitomas grade III (28%,glioblastoma multiforme (64%, high gradeoligodendrogliomas (5% and high gradeependimomas (3%. The global survivalrate was 47 % at 12 months, 26,3% at 18months and 16,7% at 24 months. The ageand type of surgery are prognostic factorsthat significantly influenced the survival at12, 18 and 24 months (9,3 months age 65 years; 9,2months GTR versus 6,4 months STR-at 12months monitoring; 11,7 months age 65; 11,5 monthsGTR versus 7,1 months STR-at 18 monthsmonitoring; 12,8 months age 65; 12,6 months GTR versus7,5 months STR –at 24 monthsmonitoring.Conclusions: Our study shows that longterm postoperative outcome after radicalsurgical resection are better than the resultsof either partial resection or simple biopsy;in terms of duration of survival (thedifference of mean survival at 12, 18 and 24months monitoring was 2,8 months, 4,4months and 5,1 months respectively infavour of patients with gross total removal .

  12. Prevalence and pattern of glenohumeral injuries among acute high-grade acromioclavicular joint instabilities. (United States)

    Pauly, Stephan; Kraus, Natascha; Greiner, Stefan; Scheibel, Markus


    With increasing numbers of arthroscopically assisted acromioclavicular (AC) joint stabilization procedures has come an increase in reports of concomitant glenohumeral injuries among AC joint separations. The aim of the present study was to evaluate the prevalence, pattern, and cause of glenohumeral pathologies among a large patient population with acute high-grade AC joint instability. A total of 125 patients (13 women, 112 men) with high-grade AC joint dislocation (6 Rockwood II; 119 Rockwood V) underwent diagnostic glenohumeral arthroscopy before AC joint repair. Pathologic lesions were evaluated for acute or degenerative origin and, if considered relevant, treated all-arthroscopically. Concomitant glenohumeral pathologies were found in 38 of 125 patients (30.4%). Analysis of pathogenesis distinguished different patterns of accompanying injuries: acute intra-articular lesions, related to the recent shoulder trauma, were found in 9 patients (7.2%), degenerative lesions, considered to be unrelated to the recent trauma, were found in 18 (14.4%), and 11 (8.8%) had an unclear traumatic correlation (intermediate group). Within the acute and the degenerative group, affected structures were predominantly partial, articular-sided tears of the anterosuperior rotator cuff, including instabilities of the pulley complex, followed by pathologies of the long head of the biceps and superior labrum anteroposterior lesions. The intermediate group presented mainly with articular-sided partial tears of the subscapularis tendon. This prospective study showed a high prevalence (30%) of concomitant glenohumeral pathologies, of which some indicate additional surgical therapy and could be missed by an isolated open AC repair. Hence, the arthroscopic approach for AC joint stabilization allows for the diagnosis and treatment of associated intra-articular pathologies. Copyright © 2013 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.

  13. Seizure prognosis of patients with low-grade tumors. (United States)

    Kahlenberg, Cynthia A; Fadul, Camilo E; Roberts, David W; Thadani, Vijay M; Bujarski, Krzysztof A; Scott, Rod C; Jobst, Barbara C


    Seizures frequently impact the quality of life of patients with low grade tumors. Management is often based on best clinical judgment. We examined factors that correlate with seizure outcome to optimize seizure management. Patients with supratentorial low-grade tumors evaluated at a single institution were retrospectively reviewed. Using multiple regression analysis the patient characteristics and treatments were correlated with seizure outcome using Engel's classification. Of the 73 patients with low grade tumors and median follow up of 3.8 years (range 1-20 years), 54 (74%) patients had a seizure ever and 46 (63%) had at least one seizure before tumor surgery. The only factor significantly associated with pre-surgical seizures was tumor histology. Of the 54 patients with seizures ever, 25 (46.3%) had a class I outcome at last follow up. There was no difference in seizure outcome between grade II gliomas (astrocytoma grade II, oligodendroglioma grade II, mixed oligo-astrocytoma grade II) and other pathologies (pilocytic astrocytoma, ependymomas, DNET, gangliocytoma and ganglioglioma). Once seizures were established seizure prognosis was similar between different pathologies. Chemotherapy (p=0.03) and radiation therapy (p=0.02) had a positive effect on seizure outcome. No other parameter including significant tumor growth during the follow up period predicted seizure outcome. Only three patients developed new-onset seizures after tumor surgery that were non-perioperative. Anticonvulsant medication was tapered in 14 patients with seizures and 10 had no further seizures. Five patients underwent additional epilepsy surgery with a class I outcome in four. Two patients received a vagal nerve stimulator with >50% seizure reduction. Seizures at presentation are the most important factor associated with continued seizures after tumor surgery. Pathology does not influence seizure outcome. Use of long term prophylactic anticonvulsants is unwarranted. Chemotherapy and

  14. HPV 16 and cigarette smoking as risk factors for high-grade cervical intra-epithelial neoplasia. (United States)

    Ho, G Y; Kadish, A S; Burk, R D; Basu, J; Palan, P R; Mikhail, M; Romney, S L


    Although genital human papillomavirus (HPV) infection is well established as the etiologic agent for cervical intraepithelial neoplasia (CIN), little is known about the cofactors involved in the development of high-grade lesions or the progression of low-grade to high-grade lesions. In our study of HPV-infected women with CIN (163 CIN I, 51 CIN II and 44 CIN III), women with CIN II or III were compared with those with CIN I for risk factors associated with high-grade lesions. After controlling for age, education, ethnicity and frequency of Pap smear screening, infection with HPV 16, but not high viral load or infection with multiple types, was associated with high-grade lesions (OR for CIN II = 11.96, OR for CIN III = 23.74). Risk of CIN III, but not CIN II, increased with number of cigarettes smoked per day (ORs = 1.49 and 3.35 for 10 cigarettes per day, respectively) and decreased with frequency of condom use during sex (ORs = 0.60 and 0.32 for women who used condoms occasionally/sometimes and most/all of the time, respectively). There were no associations between high-grade lesions and plasma levels of micronutrients (retinol, beta-carotene, alpha-tocopherol and reduced ascorbic acid). Our results indicate that infection with HPV 16 is associated with high-grade lesions. Additional cofactors, such as cigarette smoking, may be required as a carcinogen to advance HPV-infected cells toward neoplastic progression.

  15. Critical Thinking Skills of an Eighth Grade Male Student with High Mathematical Ability in Solving Problem (United States)



    This study aims to describe student’s critical thinking skill of grade VIII in solving mathematical problem. A qualitative research was conducted to a male student with high mathematical ability. Student’s critical thinking skill was obtained from a depth task-based interview. The result show that male student’s critical thinking skill of the student as follows. In understanding the problem, the student did categorization, significance decoding, and meaning clarification. In devising a plan he examined his ideas, detected his argument, analyzed his argument and evaluated his argument. During the implementation phase, the skill that appeared were analyzing of the argument and inference skill such as drawing conclusion, deliver alternative thinking, and problem solving skills. At last, in rechecking all the measures, they did self-correcting and self-examination.


    Directory of Open Access Journals (Sweden)

    Jumbuh Prabowo


    Full Text Available To fulfill the demand of the advance of Information Technology, this present study involved multimedia for writing courseware. This study examined teacher’s and students’ responses to the use of interactive multimedia. The participants of this were one immersion class of 8th grade students and an English teacher of a junior high school in Purwokerto, Central Java. These students were selected purposively. There were two instruments used in this study: questionnaire and observational sheet. It can be concluded that regarding to the teacher’s and students’ responses to the use of interactive multimedia, it is found out that both teacher and the students responded positively. They were interested in the courseware because this multimedia was different from those used in class.

  17. Health-related quality of life in patients with high-grade gliomas

    DEFF Research Database (Denmark)

    Piil, K; Jakobsen, J; Christensen, Karl Bang


    The diagnosis of a high-grade glioma usual is followed by functional impairment(s), cognitive decline and an impaired psycho-social well-being. This might well have a significant and negative impact on the health related quality of life. The purpose of this study was to explore physical activity...... levels, prevalence and severity of anxiety and depressive symptoms and health-related quality of life among patients with a highgrade glioma. This paper is based on a longitudinal mixed methods study. Patients (n = 30) completed questionnaires at 5 time points from time of diagnosis until the final...... follow-up after 1 year. Scores of Karnofsky Performance Status (KPS), physical activity, anxiety and depression and health-related quality of life (FACT-Br) are obtained. Patients' physical activity level and KPS decrease during the disease- and treatment trajectory. The majority of patients did...

  18. Total Artificial Heart Implantation After Undifferentiated High-Grade Sarcoma Excision. (United States)

    Kremer, Jamila; Farag, Mina; Arif, Rawa; Brcic, Andreas; Sabashnikov, Anton; Schmack, Bastian; Popov, Aron-Frederik; Karck, Matthias; Dohmen, Pascal M; Ruhparwar, Arjang; Weymann, Alexander


    BACKGROUND Total artificial heart (TAH) implantation in patients with aggressive tumor infiltration of the heart can be challenging. CASE REPORT We report on a patient with a rare primary undifferentiated high-grade spindle cell sarcoma of the mitral valve and in the left atrium, first diagnosed in 2014. The referring center did a first resection in 2014. In the course of 17 months, computer tomography (CT) scan again showed massive invasion of the mitral valve and left atrium. Partial resection and mitral valve replacement was not an option. We did a subtotal heart excision with total artificial heart implantation. In this report we discuss complications, risk factors, and perioperative management of this patient. CONCLUSIONS Patients with aggressive tumors of the heart can be considered for TAH implantation.

  19. Cerebral Connectivity and High-grade Gliomas: Evolving Concepts of Eloquent Brain in Surgery for Glioma

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    Sanjay Konakondla


    Full Text Available Technological advances in imaging the human brain help us map and understand the intricacies of cerebral connectivity. Current techniques and specific imaging sequences, however, do come with limitations. Image resolution, variability of techniques and interpretation of images across institutions are just a few concerns. In the setting of high-grade gliomas, understanding how these pathways are affected during tumor growth, surgical resection, and in the brain plasticity presents an even greater challenge. Clinical symptoms, tumor growth, and intraoperative electrical stimulation are important peri-operative considerations to assist in determining neuronal re-wiring and establish a basis of anatomic and functional correlation. The application of functional mapping coupled with the understanding of the natural history of gliomas and implications of neural plasticity, is critical in achieving the goals of maximal tumor resection while minimizing post operative deficits and improving quality of life.

  20. A High-Grade Chondrosarcoma of Calcaneum Mimicking as a Benign Pathology: Delayed Diagnosis and Management. (United States)

    Baba, Muzamil Ahmad; Nazir, Naila; Shabeer, Maajid; Mir, Bashir Ahmed; Kawoosa, Altaf Ahmad


    This case is presented to highlight a rare case of chondrosarcoma of calcaneum in a young adult mimicking as a benign pathology and to highlight the diagnosis and early management of such cases to prevent complications and even death. Chondrosarcoma constitutes less than 10% of all primary malignancies of bone and occurs mostly in proximal locations such as pelvis, proximal femur, and proximal humerus. We present a case of high-grade chondrosarcoma at a very rare site, calcaneum of a 40-year-old male that was mimicking as a benign pathology. This case report highlights the importance of proper clinical examination, evaluation, and suspicion for benign occurring lesions to prevent complications related to a delay in diagnosis. Therapeutic, Level IV: Case study. © 2016 The Author(s).

  1. Developing Problem-Based Learning (PBL Worksheets for the Eight Grade Students at Junior High School

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    Isrokijah Isrokijah


    Full Text Available This study aims at developing problem-based learning (PBL worksheets for the eighth grade students at junior high school. It belongs to Borg & Gall’s research and development R & D, involving 35 students from one class as the subjects. Interview guide for the teachers and questionnaire for the students were employed to collect data in needs analysis, and checklist in validation and try-out stages. The qualitative data collected through interview was analyzed descriptively, while, the quantitative data collected through questionnaire and checklist was analyzed using statistic descriptive by counting the frequency of appearance of the response. Finally the result of the data analysis was synthesized to get the real picture about the teachers’ and students’ response towards the use of PBL worksheets in learning English.   DOI:

  2. Advanced technologies for manufacturing high strength sour grade UOE line pipe

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Kenji; Omura, Tomohiko; Takahashi, Nobuaki; Minato, Izuru; Yamamoto, Akio [Sumitomo Metal Industries, Ltd., Kashima, (Japan)


    A new kind of high strength pipeline has been manufactured for sour service in offshore pipelines. This paper first presents a review of developments in manufacturing technology to improve sour resistance. This was particularly the case with Grade UOE line pipe. The improvement was achieved by optimizing the continuous casting process, monitoring the shape of inclusions (such as MnS, CaS, Al2O3, CaO-Al2O3) and decreasing coarse precipitates (Nb(C,N), TiN). The study then used the HIC evaluation method to determine hydrogen induced cracking (HIC) resistance of the material and HAZ test for sulfide stress cracking (SSC) resistance. The evaluation of the NACE TM0284 solution A showed that these pipelines are able to resist severe sour conditions because of good HIC and SSC resistance. Optimizing others components like alloying elements and the ACC process would improve sour resistance in future applications.

  3. Daily Life Experiences of Patients With a High-Grade Glioma and Their Caregivers

    DEFF Research Database (Denmark)

    Piil, Karin; Juhler, Marianne; Jakobsen, Johannes


    BACKGROUND: There is a lack of knowledge regarding the breadth of needs for rehabilitation and supportive care across the disease and treatment trajectory for patients with a high-grade glioma (HGG) and their caregivers. OBJECTIVE: The aim of this study was to elucidate the experiences and needs...... for rehabilitation and supportive care in patients with HGG and their caregivers. METHODS: Patients with malignant glioma (N = 30) and their caregivers (N = 33) were interviewed five times during the first year of the HGG trajectory. A thematic analysis of interviews at five time points revealed five main themes...... describing the experiences related to the illness trajectory and needs for rehabilitation and supportive care. RESULTS: The five main themes identified were (a) individual strategy for acquiring prognostic information, (b) shared hope, (c) engagement in health promotion activities, (d) adjustment to symptom...

  4. Patient Outcomes in the Operative and Nonoperative Management of High-Grade Spondylolisthesis in Children

    DEFF Research Database (Denmark)

    Lundine, K. M.; Lewis, S. J.; Al-Aubaidi, Zaid


    (SRS)-30 questionnaire.Results:Fifty-three patients were identified for inclusion in the study and 49 were contacted for 92% follow-up. Twenty-four patients were treated with operative intervention, and 25 patients were initially treated nonoperatively, but 10 went on to require surgical intervention....... Mean age at presentation was 12.6 years (range, 8 to 17 y) and mean age at follow-up was 20.1 years (range, 10 to 29 y). There were no outcome differences between the groups. A more kyphotic slip angle was associated with worse SRS-30 outcome scores across all groups. In the nonoperative group...... SRS-30 outcome scores.Conclusions:Nonoperative management or watchful waiting of the minimally symptomatic or asymptomatic child with a high-grade spondylolisthesis is safe and does not lead to significant problems. Operative intervention for the symptomatic patient achieves similar long-term results...

  5. Unusual presentation of unilateral intra-orbital optic nerve pilocytic astrocytoma of the juvenile type in a geriatric patient. (United States)

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


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

  6. Preparation of High-Grade Powders from Tomato Paste Using a Vacuum Foam Drying Method. (United States)

    Sramek, Martin; Schweiggert, Ralf Martin; van Kampen, Andreas; Carle, Reinhold; Kohlus, Reinhard


    We present a rapid and gentle drying method for the production of high-grade tomato powders from double concentrated tomato paste, comparing results with powders obtained by foam mat air drying and freeze dried powders. The principle of this method consists of drying tomato paste in foamed state at low temperatures in vacuum. The formulations were dried at temperatures of 50, 60, and 70 °C and vacuum of 200 mbar. Foam stability was affected by low serum viscosity and the presence of solid particles in tomato paste. Consequently, serum viscosity was increased by maltodextrin addition, yielding optimum stability at tomato paste:maltodextrin ratio of 2.4:1 (w/w) in dry matter. Material foamability was improved by addition of 0.5% (w/w, fresh weight) egg white. Because of solid particles in tomato paste, foam air filling had to be limited to critical air volume fraction of Φ = 0.7. The paste was first pre-foamed to Φ = 0.2 and subsequently expanded in vacuo. After drying to a moisture content of 5.6% to 7.5% wet base (w.b.), the materials obtained were in glassy state. Qualities of the resulting powders were compared with those produced by freeze and air drying. Total color changes were the least after vacuum drying, whereas air drying resulted in noticeable color changes. Vacuum foam drying at 50 °C led to insignificant carotenoid losses, being equivalent to the time-consuming freeze drying method. In contrast, air drying caused lycopene and β-carotene losses of 18% to 33% and 14% to 19% respectively. Thus, vacuum foam drying enables production of high-grade tomato powders being qualitatively similar to powders obtained by freeze drying. © 2015 Institute of Food Technologists®

  7. Metal recovery from high-grade WEEE: a life cycle assessment. (United States)

    Bigum, Marianne; Brogaard, Line; Christensen, Thomas H


    Based on available data in the literature the recovery of aluminium, copper, gold, iron, nickel, palladium and silver from high-grade WEEE was modeled by LCA. The pre-treatment of WEEE included manual sorting, shredding, magnetic sorting, Eddy-current sorting, air classification and optical sorting. The modeled metallurgical treatment facility included a Kaldo plant, a converter aisle, an anode refinery and a precious metal refinery. The metallurgic treatment showed significant environmental savings when credited the environmental load from avoided production of the same amount of metals by mining and refining of ore. The resource recovery per tonne of high-grade WEEE ranged from 2g of palladium to 386kg of iron. Quantified in terms of person-equivalents the recovery of palladium, gold, silver, nickel and copper constituted the major environmental benefit of the recovery of metals from WEEE. These benefits are most likely underestimated in the model, since we did not find adequate data to include all the burdens from mining and refining of ore; burdens that are avoided when metals are recovered from WEEE. The processes connected to the pre-treatment of WEEE were found to have little environmental effect compared to the metallurgical treatment. However only 12-26% of silver, gold and palladium are recovered during pre-treatment, which suggest that the reduction of the apparent losses of precious metals as palladium, gold and silver during pre-treatment of WEEE is of environmental importance. Our results support in a quantitative manner that metal recovery from WEEE should be quantified with respect to the individual metals recovered and not as a bulk metal recovery rate. Copyright © 2011 Elsevier B.V. All rights reserved.


    Yang, Xi; Kong, Qingquan; Song, Yueming; Liu, Limin; Li, Tao; Gong, Quan; Zeng, Jiancheng; Liu, Hao


    To observe the character of spino-pelvic sagittal alignment in patients with high-grade L5 isthmic spondylolisthesis, and to analyze the sagittal alignment alteration after operation. Between January 2009 and June 2014, 25 patients with high-grade L5 isthmic spondylolisthesis underwent posterior surgery, and the clinical data were retrospectively analyzed as study group. There were 14 males and 11 females with a mean age of 42.5 years (range, 20-65 years). The mean disease duration was 6 months (range, 3-12 months). According to the Meyerding evaluating system, 15 cases were rated as degree III, and 10 cases as degree IV. Eighty healthy adult volunteers were recruited simultaneously as control group. The lumbar sacral angle (LSA), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), lumbar lordosis (LL), thoracic kyphosis (TK), and sagittal vertical axis (SVA) were measured on preoperative and last follow-up standing full length lateral X-ray films. And these parameters were compared between study group (preoperative parameters) and control group. Then the patients in study group were divided into 2 subgroups according to Hresko's method: the balanced pelvis subgroup (n = 14) and unbalanced pelvis subgroup (n = 11). The sagittal parameters were compared between 2 subgroups, and the alteration of sagittal parameters before surgery and at last follow-up was analyzed in each subgroup respectively. All patients in study group were followed up 18 months on average (range, 6-48 months). After surgery, spondylolisthesis was reduced from degree III to degree 0 in 12 cases and to degree I in 3 cases, and from degree IV to degree 0 in 6 cases and to degree I in 4 cases. Bone fusion was obtained in all patients at last follow-up. The preoperative PI, SS, PT, and SVA of study group were significantly greater than those of control group (P spondylolisthesis have greater PI, abnormal lumbosacral kyphosis, and sagittal imbalance.

  9. Surgical Versus Nonsurgical Treatment for High-Grade Spondylolisthesis in Children and Adolescents (United States)

    Xue, Xuhong; Wei, Xiaochun; Li, Li


    Abstract The optimal management of high-grade spondylolisthesis in children and adolescent is controversial. There is a paucity of literature regarding operatively or nonoperative management in this setting. To assessment of the current state of evidence regarding high-grade spondylolisthesis treatment with the goal of obtaining outcome comparisons in these patients managed either operatively or nonoperatively. We performed a systematic literature search up to November 2014, using Medline, Embase, and The Cochrane Library. The analysis and eligibility criteria were documented according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA-guidelines) and Cochrane Back Review Group editorial board. We used the Newcastle–Ottawa quality assessment scale (NOS-scale) to assess the quality. Five observational studies were considered eligible for analysis based on the evaluation of 1596 identified papers. The mean overall difference in the Scoliosis Research Society questionnaire 22 between the surgical and nonsurgical groups was not statistically significant (95% CI: −0.17 to 0.21, P = 0.84). The pooled mean difference in progression of slip between the surgical and nonsurgical groups was no significant difference (OR: 0.47, 95% CI: 0.12–1.81, P = 0.27, I2 = 0%). Because of the preponderance of uncontrolled case series, low-quality evidence indicates that the quality of life and progression of slips was no significant difference between surgery and nonoperation group. Nonoperative patients had no radiologic progression of their slip during the follow-up period. PMID:26986134

  10. Efficacy of spermatic vein ligation in patients affected by high grade left varicocele

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    Marco Grasso


    Full Text Available Purpose: To study the effect of high grade varicocele treatment in infertile patients. Materials and Methods: Seventy-five patients were selected by the following criteria: infertility persisting for more than 1 year; abnormal semen parameters; no other infertility-related disease; no obvious causes of infertility in the subject’s partner; basal eco-color Doppler ultrasound demonstrating continuous reflux in the spermatic vein. All patients considered for the study had at least a six months period from the diagnosis to the surgery due to waiting list, choice of the patient or time needed to complete diagnostic evaluation of the couple. The surgical procedure was performed through an inguinal approach. All enrolled patients were counseled to have unprotected intercourse during the ovulation period in order to maximize the probability of pregnancy within the 6-month preoperative period. The achievement of pregnancy and semen parameters were recorded during the preoperative and postoperative period. Results: Two of the seventy-five patients were excluded because of persistent varicocele after surgery. The preoperative pregnancy rate was 1.3% (1 couple. The postoperative pregnancy rate was 42.5%. The stratification of pregnancies by semester showed a significantly higher rate in the first postoperative period (p = 0.0012. Mean time to conception was 13.5 months. Mean preoperative sperm count was 17.6x10 6 /mL compared to 19.7x10 6 /mL in the postoperative period (p < 0.0001. Mean percentage of progressive sperm motility was 13.7%, compared to 17.6% in the postoperative period (p < 0.0001. Mean percentage of normal sperm morphology was 7.6%, compared to 15.2% postoperatively (p < 0.0001. Conclusion: Surgical treatment of high grade varicocele proved to effectively treat associated infertility by improving seminal parameters and pregnancy rate in our patient cohort.

  11. Predicting Freshman Grade Point Average From College Admissions Test Scores and State High School Test Scores

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    Daniel Koretz


    Full Text Available The current focus on assessing “college and career readiness” raises an empirical question: How do high school tests compare with college admissions tests in predicting performance in college? We explored this using data from the City University of New York and public colleges in Kentucky. These two systems differ in the choice of college admissions test, the stakes for students on the high school test, and demographics. We predicted freshman grade point average (FGPA from high school GPA and both college admissions and high school tests in mathematics and English. In both systems, the choice of tests had only trivial effects on the aggregate prediction of FGPA. Adding either test to an equation that included the other had only trivial effects on prediction. Although the findings suggest that the choice of test might advantage or disadvantage different students, it had no substantial effect on the over- and underprediction of FGPA for students classified by race-ethnicity or poverty.

  12. Patients with high-grade pivot-shift phenomenon are associated with higher prevalence of anterolateral ligament injury after acute anterior cruciate ligament injuries. (United States)

    Song, Guan-Yang; Zhang, Hui; Wu, Guan; Zhang, Jin; Liu, Xin; Xue, Zhe; Qian, Yi; Feng, Hua


    To compare the prevalence of concomitant anterolateral ligament (ALL) injury between patients with high-grade (grades II and III) pivot-shift and those with low-grade (grades 0 and I) pivot-shift phenomenon after acute anterior cruciate ligament (ACL) injuries. Sixty-eight patients with an acute ACL injury who showed high-grade (grades II and III) pivot-shift phenomenon were enrolled as the study group. They were matched in a 1:1 fashion to another 68 ACL-injured control participants who showed low-grade (grades 0 and I) pivot-shift phenomenon during the same study period. Patients were matched by age, sex, and time from injury to surgery. A standardized pivot-shift test was performed under anesthesia for all the patients. Two blinded musculoskeletal radiologists reviewed the magnetic resonance imaging (MRI) scans for the presence of concomitant ALL injury. The grade of an ALL injury was divided into grade 0 (normal), grade I (sprain), grade II (partial tear), and grade III (complete tear). The prevalence and the grade of concomitant ALL injury were further compared between the study group and the control group. Overall, the prevalence of concomitant ALL injury in the study group (94.1%, 64/68) was significantly higher than that in the control group [60.3%, (41/68), P < 0.05]. Specifically, there were 49 patients (49/64, 76.6%) who showed grade II/III (partial/complete tear) MRI evidence of concomitant ALL injury, which was also significantly higher than that in the control group (12/41, 29.3%). Patients with high-grade pivot-shift phenomenon showed higher prevalence of concomitant ALL injury compared to those with low-grade pivot-shift phenomenon after acute ACL injuries. Careful assessment and proper treatment of this concomitant injury should be considered especially in knees with high-grade pivot-shift phenomenon. III.

  13. “Low-grade squamous intraepithelial lesion, cannot exclude high-grade:” TBS says “Don't Use It!” should I really stop it?

    Directory of Open Access Journals (Sweden)

    Jeanine M Chiaffarano


    Full Text Available Background: The Bethesda System uses a two-tiered approach in the diagnosis of cervical squamous intraepithelial lesions (SILs. Occasionally, Papanicolaou (Pap tests with evident low-grade SIL (LSIL also have some features suggestive but not diagnostic of high-grade SIL (HSIL. This study reviews our experience with “Low-grade Squamous Intraepithelial Lesion, Cannot Exclude High-grade” (LSIL-H and discusses the best approach to report such Paps if the LSIL-H interpretation is abandoned. Methods: Abnormal Paps were identified between January and December 2014 that had surgical follow-up within 6 months. Their biopsy outcomes were compared. Statistical analysis was performed using Pearson's Chi-square and McNemar tests in SPSS software version 23. Statistical significance was defined as P ≤ 0.05. Results: There were a total of 1049 abnormal Paps with follow-up. High-grade dysplasia/carcinoma (HGD+ was found in 8% of LSIL, 30% of LSIL-H, 52% of atypical squamous cells (ASCs, cannot rule out HSIL (ASC-H, and 77% of HSIL Paps. The detection rate of HGD+ for LSIL-H was between that of LSIL (Pearson's Chi-square test, P = 0.000 and ASC-H (P = 0.04. If LSIL-H cases are reported as ASC-H, the rate of HGD+ for the ASC-H category would decrease from 51.5% to 37.4% (McNemar test, P = 0.000. Alternatively, if LSIL-H cases are downgraded to LSIL, the rate of HGD+ for the LSIL category would rise from 7.7% to 10.4% (McNemar test, P = 0.000. Nearly 86.7% of LSIL-H cases were positive for high-risk HPV (HR-HPV in comparison to 77.5% of LSILs, 100% of ASC-Hs, and 75% of HSILs. The sample size for HR-HPV and LSIL-H was too small for meaningful statistical analysis. Conclusions: “LSIL-H” category detects more HGD+ than LSIL, and fewer than ASC-H and HSIL. If LSIL-H is eliminated, Paps with this finding are best reported as ASC-H to ensure that women with potential HGD+ undergo colposcopy in a timely manner. Reporting LSIL-H as LSIL may delay colposcopy

  14. Is Age an Independent Predictor of High-Grade Histopathology in Women Referred for Colposcopy after Abnormal Cervical Cytology? (United States)

    Kingnate, Chalita; Supoken, Amornrat; Kleebkaow, Pilaiwan; Chumworathayi, Bundit; Luanratanakorn, Sanguanchoke; Kietpeerakool, Chumnan


    This study was conducted to determine whether advancing age is an independent predictor of increased risk of high-grade pathologies among women referred for colposcopy after abnormal cervical cytology. Medical records were reviewed for women with abnormal cervical cytology who underwent colposcopy at Khon Kaen University Hospital. Logistic regression was used to determine the independent impact of age on the risk of high-grade pathologies. Mean age of the women was 42.8 years. Of 482 women, 97 (20.1%) were postmenopausal, and 92 (19.1%) were nulliparous. The rate of high-grade pathologies included cervical intraepithelial neoplasia 2-3, 99 (20.5%), adenocarcinoma in situ, 4 (0.8%), cervical cancer, 30 (6.2%), and endometrial cancer, 1 (0.2%). The prevalence of significant lesions was 26.9% (95% CI, 23.1%-31.2%). In total, 31 women had cancers (6.4%; 95% CI, 4.4%-9.0%). When controlling for smear types and parity, age was noted to be a significant independent predictor of high-grade histopathology. Women older than 35-40 years were approximately 2 times as likely to have severe histopathology as the younger women. This study illustrates the substantial risk of underlying significant lesions especially invasive cancer in Thai women with abnormal cervical cytology. Age was a significant independent factor predicting the risk of high-grade pathologies.

  15. Realization of high heat flux tungsten monoblock type target with graded interlayer for application to DEMO divertor (United States)

    Richou, M.; Gallay, F.; Böswirth, B.; Chu, I.; Lenci, M.; Loewenhoff, Th; Quet, A.; Greuner, H.; Kermouche, G.; Meillot, E.; Pintsuk, G.; Visca, E.; You, J. H.


    The divertor is the key in-vessel plasma-facing component being in charge of power exhaust and removal of impurity particles. In DEMO, divertor targets must survive an environment of high heat fluxes (˜up to 20 MW m-2 during slow transients) and neutron irradiation. One advanced concept for components in monoblock configuration concerns the insertion of a compositionally graded layer between tungsten and CuCrZr instead of the soft copper interlayer. As a first step, a thin graded layer (˜25 μm) was developed. As a second step, a thicker graded layer (˜500 μm), which is actually being developed, will also be inserted to study the compliant role of a macroscopic graded layer. This paper reports the results of cyclic high heat flux loading tests up to 20 MW m-2 and to heat flux higher than 25 MW m-2 that mock-ups equipped with thin graded layer survived without visible damage. First feedback on manufacturing steps is also presented. Moreover, the first results obtained on the development of the thick graded layer and its integration in a monoblock configuration are shown.

  16. Sequential proton boost after standard chemoradiation for high-grade glioma. (United States)

    Adeberg, Sebastian; Bernhardt, Denise; Harrabi, Semi Ben; Uhl, Matthias; Paul, Angela; Bougatf, Nina; Verma, Vivek; Unterberg, Andreas; Wick, Wolfgang; Haberer, Thomas; Combs, Stephanie E; Herfarth, Klaus; Debus, Juergen; Rieken, Stefan


    To retrospectively assess the feasibility and safety of a sequential proton boost following conventional chemoradiation in high-grade glioma (HGG). Sixty-six consecutive patients with HGG were treated with 50.0 Gy photons (50.0-50.4 Gy) in 2.0 Gy (1.8-2.0 Gy) fractions, followed by a proton boost with 10 Gy equivalent (Gy(RBE)) in 2.0 Gy(RBE) fractions. Patients were matched one to one with 66 patients with HGG undergoing conventional radiation therapy (RT) with 60.0 Gy photons (59.4-60.0 Gy) in 2.0 Gy fractions (1.8-2.0 Gy). Matching criteria were age, WHO grade, Karnofsky's performance status, PTV size, temozolomide therapy (each p > 0.1). The study assessed progression-free survival (PFS), overall survival (OS), acute treatment-related toxicity (CTCAE v.4.03) and pseudoprogression (RANO criteria). Median PFS and OS were similar in both treatment groups (bimodality RT, PFS: 8.8 months [2-32 months], OS 19.1 months [4-41 months]; photon-only RT, PFS: 7.2 months [2-39 months], 20.9 months [3-53 months]; p = 0.430 and p = 0.125). The median PTV of the proton boost was significantly smaller than the photon plan PTVs (each p compared to photon-only plans, yielded comparable progression and survival rates at lower CTCAE grade 3 acute toxicity rates. Pseudoprogression occurred rarely and evenly distributed in both treatment groups. Thus, bimodality RT was at least equivalent regarding outcome and potentially superior with respect to toxicity in patients with HGG. Treating patients with HGG with 50.0 Gy photons in 2.0 Gy fractions, followed by a proton boost with 10 Gy(RBE) in 2.0 Gy(RBE) fractions, is safe and feasible. Severe radiation-induced acute toxicity and pseudoprogression were rare in both treatment groups. Therefore, in this clinical setting, combined proton radiotherapy might be beneficial in terms of further risk reduction for treatment-related side effects. Interestingly, treatment volume reduction

  17. Physical activity behavior and related characteristics of highly-active 8th grade girls (United States)

    Taverno Ross, Sharon E.; Dowda, Marsha; Beets, Michael W.; Pate, Russell R.


    Purpose While girls are generally less physically active than boys, some girls regularly engage in high levels of physical activity (PA); however, very little is known about these girls and how they differ from those who are less physically active. This study examined the PA behavior and related characteristics of highly-active adolescent girls and compared them with those who are less active. Methods Data from 1,866 8th grade girls from 6 field centers across the U.S. participating in the Trial of Activity for Adolescent Girls (TAAG) were included in the present analysis. Mixed model ANOVAs examined differences in sociodemographic, anthropometric, psychosocial, and physical activity (accelerometry and self-report) variables between high- and low-active girls; effect sizes were calculated for the differences. Results High-active girls were taller, had lower BMIs and body fat, and were less sedentary. High-active girls scored higher on self-efficacy, enjoyment of PA, self-management strategies, outcome-expectancy value, and support from family and friends than low-active girls. Low-active girls participated in more leisure-time and educational sedentary activities than high-active girls. High-active girls participated in more PA classes/lessons outside of school, team sports, and individual sports. They were also more likely to participate in sports in an organized setting in the community or at school than low-active girls. Conclusions Health promotion efforts should focus on decreasing the amount of time girls spend in sedentary activities and replacing that time with organized PA opportunities; such efforts should seek to minimize perceived barriers and increase self-efficacy and support for PA. PMID:23384978

  18. MEG network differences between low- and high-grade glioma related to epilepsy and cognition.

    Directory of Open Access Journals (Sweden)

    Edwin van Dellen

    Full Text Available OBJECTIVE: To reveal possible differences in whole brain topology of epileptic glioma patients, being low-grade glioma (LGG and high-grade glioma (HGG patients. We studied functional networks in these patients and compared them to those in epilepsy patients with non-glial lesions (NGL and healthy controls. Finally, we related network characteristics to seizure frequency and cognitive performance within patient groups. METHODS: We constructed functional networks from pre-surgical resting-state magnetoencephalography (MEG recordings of 13 LGG patients, 12 HGG patients, 10 NGL patients, and 36 healthy controls. Normalized clustering coefficient and average shortest path length as well as modular structure and network synchronizability were computed for each group. Cognitive performance was assessed in a subset of 11 LGG and 10 HGG patients. RESULTS: LGG patients showed decreased network synchronizability and decreased global integration compared to healthy controls in the theta frequency range (4-8 Hz, similar to NGL patients. HGG patients' networks did not significantly differ from those in controls. Network characteristics correlated with clinical presentation regarding seizure frequency in LGG patients, and with poorer cognitive performance in both LGG and HGG glioma patients. CONCLUSION: Lesion histology partly determines differences in functional networks in glioma patients suffering from epilepsy. We suggest that differences between LGG and HGG patients' networks are explained by differences in plasticity, guided by the particular lesional growth pattern. Interestingly, decreased synchronizability and decreased global integration in the theta band seem to make LGG and NGL patients more prone to the occurrence of seizures and cognitive decline.

  19. The challenges of management of high-grade gliomas in Nigeria

    Directory of Open Access Journals (Sweden)

    Chika Anele Ndubuisi


    Full Text Available Background: High-grade gliomas (HGG are among the most challenging brain tumors despite many research efforts worldwide. Aim: The aim of this study was to evaluate the local challenges that may influence outcome of HGG managed in a neurosurgical center in Nigeria. Methodology: Retrospective analysis of prospectively recorded data of patients managed for intracranial HGG at Memfys Hospital for Neurosurgery, Enugu, Nigeria, between the year 2006 and 2015. Only cases with conclusive histology following surgery were analyzed. Results: Glioma was 60 (23.8% of 252 histology confirmed brain tumors. HGG represented 53.8% of gliomas with male:female ratio of 2.2:1.0 and peaked from fifth decade of life. Glioblastoma multiforme accounted for 69% of HGG. At 1-year postsurgery, 53% of HGGs were dead and 88% of these deaths were in the World Health Organization Grade IV group. Only 40% of cases could receive adjuvant treatment with only 15% mortality at 1 year in this subgroup that received adjuvant therapy. In addition, 19% of cases had surgery at Karnofsky score (Ks of ≥70%. However, 94% of mortality at 1 year was related to surgery at Ks of ≤60%. Only four patients had a tumor volume of ≤50 cm3, and among these cases, three patients were independent at 1 year. Patients with tumor volume above 50 cm3 accounted for 94% of mortality. Conclusion: The peak age incidence for HGG seems to be lower than in Caucasians. Most cases present late with poor Ks and big tumor volume. The proportion with access to adjuvant treatment is still poor. Preoperative Karnofsky, extent of resection, duration of hospital, and Intensive Care Unit stay have impact on outcome.

  20. Arthroscopically assisted stabilization of acute high-grade acromioclavicular joint separations. (United States)

    Scheibel, Markus; Dröschel, Silvia; Gerhardt, Christian; Kraus, Natascha


    The purpose of this study was to evaluate the clinical and radiological results after arthroscopically assisted and image intensifier--controlled stabilization of high-grade acromioclavicular (AC) joint separations using the double TightRope technique with the first-generation implant. The double TightRope technique using the first-generation implant leads to good clinical and radiological results by re-creating the anatomy of the AC joint. Case series; Level of evidence, 4. Thirty-seven consecutive patients (4 women and 33 men; mean age, 38.6 years) who sustained an acute AC joint dislocation grade V according to Rockwood were included in this prospective study. The Subjective Shoulder Value (SSV), the Constant Score (CS), the Taft Score (TS), and a newly developed Acromioclavicular Joint Instability Score (ACJI) were used for final follow-up. Bilateral stress views and bilateral Alexander views were taken to evaluate radiographic signs of recurrent vertical and horizontal AC joint instability. Twenty-eight patients (2 women and 26 men; mean age, 38.8 years [range, 18-66 years]) could be evaluated after a mean follow-up of 26.5 months (range, 20.1-32.8 months). The interval from trauma to surgery averaged 7.3 days (range, 0-18 days). The mean SSV reached 95.1% (range, 85%-100%), the mean CS was 91.5 points (range, 84-100) (contralateral side: mean, 92.6 points), the mean TS was 10.5 points (range, 7-12), and the ACJI averaged 79.9 points (range, 45-100). The final coracoclavicular distance was 13.6 mm (range, 5-27 mm) on the operated versus 9.4 mm (range, 4-15 mm) on the contralateral side (P partial recurrent vertical and horizontal AC joint instability.

  1. High-Temperature Refining of Metallurgical-Grade Silicon: A Review (United States)

    Johnston, Murray D.; Khajavi, Leili Tafaghodi; Li, Mark; Sokhanvaran, Samira; Barati, Mansoor


    Among currently known alternatives for renewable energy sources, solar power is generally regarded as having the most potential to satisfy the ever-growing demand. While solar photovoltaic power is a well-established technology, its widespread uptake has been hindered by the prohibitively high price of units and thus electricity. This is due mainly to the high cost of the silicon used to fabricate the devices. This article presents a review of the development of established pyrometallurgical techniques as applied to refining metallurgical silicon to solar grade for the purposes of reducing reliance on expensive traditional silicon feedstock. Four basic high-temperature methods—solvent refining, vaporization, electrorefining, and slag treatment—are described, and the limitations and advantages of each method are presented. It is apparent that these techniques are very useful for removing impurities from silicon, but are often selective and not able to remove all problematic elements. Therefore, refining may need to be as a sequence of steps, targeting specific elements each time, or as novel methods combining multiple techniques simultaneously. Ultimately, the successful approach will have to achieve large-scale production by cost-effective means to replace current methods.

  2. High Efficiency Tandem Thin-Perovskite/Polymer Solar Cells with a Graded Recombination Layer. (United States)

    Liu, Yao; Renna, Lawrence A; Bag, Monojit; Page, Zachariah A; Kim, Paul; Choi, Jaewon; Emrick, Todd; Venkataraman, D; Russell, Thomas P


    Perovskite-containing tandem solar cells are attracting attention for their potential to achieve high efficiencies. We demonstrate a series connection of a ∼ 90 nm thick perovskite front subcell and a ∼ 100 nm thick polymer:fullerene blend back subcell that benefits from an efficient graded recombination layer containing a zwitterionic fullerene, silver (Ag), and molybdenum trioxide (MoO3). This methodology eliminates the adverse effects of thermal annealing or chemical treatment that occurs during perovskite fabrication on polymer-based front subcells. The record tandem perovskite/polymer solar cell efficiency of 16.0%, with low hysteresis, is 75% greater than that of the corresponding ∼ 90 nm thick perovskite single-junction device and 65% greater than that of the polymer single-junction device. The high efficiency of this hybrid tandem device, achieved using only a ∼ 90 nm thick perovskite layer, provides an opportunity to substantially reduce the lead content in the device, while maintaining the high performance derived from perovskites.

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

    Directory of Open Access Journals (Sweden)

    R.O. Chaves


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

  4. Mixed granular cell astrocytoma and fibrosarcoma of the brain: a case report. (United States)

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


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

  5. College Performance and Retention: A Meta-Analysis of the Predictive Validities of ACT® Scores, High School Grades, and SES (United States)

    Westrick, Paul A.; Le, Huy; Robbins, Steven B.; Radunzel, Justine M. R.; Schmidt, Frank L.


    This meta-analysis examines the strength of the relationships of ACT® Composite scores, high school grades, and socioeconomic status (SES) with academic performance and persistence into the 2nd and 3rd years at 4-year colleges and universities. Based upon a sample of 189,612 students at 50 institutions, ACT Composite scores and high school grade…

  6. Professional Staffing Levels and Fourth-Grade Student Research in Rural Schools with High-Poverty Levels (United States)

    Krueger, Karla Steege; Donham, Jean


    Rural schools in high-poverty areas are often understaffed. This descriptive phenomenological study examined fourth-grade state research projects in high-poverty rural Iowa schools to reveal the influence of school librarians' staffing levels on student learning of research skills. To determine evidence of students' critical literacy, ethical use…

  7. Alcohol Use and the Grades of Middle and High School Students: Does School Choice Have Effects? (United States)

    Austin, Wesley; Heath, Cary


    This article addresses the question of whether youth drinking leads to lower grades for public and private school students. Instrumental variables (IV) regressions are used to investigate differences in the relationship between drinking and grades based on whether students attend a public or private school. The regressions reveal that drinking…

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

    LENUS (Irish Health Repository)

    Fenton, E


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

  9. Comparison of chest radiography and high-resolution computed tomography findings in early and low-grade coal worker's pneumoconiosis. (United States)

    Savranlar, Ahmet; Altin, Remzi; Mahmutyazicioğlu, Kamran; Ozdemir, Hüseyin; Kart, Levent; Ozer, Tülay; Gündoğdu, Sadi


    High-resolution computed tomography (HRCT) is more sensitive than chest X-ray (CXR) in the depiction of parenchymal abnormalities. We aimed to present and compare CXR and HRCT findings in coal workers with and without early and low-grade coal worker's pneumoconiosis (CWP). 71 coal workers were enrolled in this study. All workers were male. The CXR and HRCT of those workers were obtained and graded by two trained readers. HRCT's were graded according to Hosoda and Shida's Japanese classification. After grading, 67 workers with CXR profusion 0/0-2/2 were included in the study. Four patients with major opacity were excluded. Profusion 0/1 to 1/1 cases were accepted as early and profusion 1/2 and 2/2 cases as low-grade pneumoconiosis. Discordance between CXR and HRCT was high. Discordance rate was found higher in the early pneumoconiosis cases with negative CXR than low-grade pneumoconiosis (60, 36 and 8%, respectively). When coal miners with normal CXR were evaluated by HRCT, six out of 10 cases were diagnosed as positive. In low-grade pneumoconiosis group, the number of patients with positive CXR but negative HRCT were low in comparison to patients with CXR negative and early pneumoconiosis findings. Most of the CXR category 0 patients (10/16) were diagnosed as category 1 by HRCT. Eleven cases diagnosed as CXR category 1 were diagnosed as category 0 (7/11) and category 2 (4/11) by HRCT. In CXR category 2 (eight cases), there were four cases diagnosed as category 1 by HRCT. Discordance between CXR and HRCT was high, especially for CXR negative and early pneumoconiosis cases. The role of CXR in screening coal workers to detect early pneumoconiosis findings should be questioned. We suggest using HRCT as a standard screening method instead of CXR to distinguish between normal and early pneumoconiosis.

  10. High-grade myxofibrosarcoma presenting at the spermatic cord after radiotherapy for prostate cancer. (United States)

    Tearada, Hiroshi; Nagata, Masao; Mugiya, Soichi; Ozono, Seiichiro


    A 72-year-old man with a history of prostate cancer presented 7 years postradiotherapy with a painless, egg-sized, rapidly growing nodule on the left groin at the radiation site. He underwent left high orchiectomy under a diagnosis of groin lymph node metastasis of prostate cancer. The tumour had penetrated deep into the internal inguinal ring and was resected as proximally as possible to the internal ring with a positive surgical margin. Macroscopically, the left testis was intact in the resected specimen. Immunohistochemical staining revealed that the tumour consisted of myxofibrosarcoma (MFS) with spindle cells; and was positive for vimentin, cytokeratin (AE1/AE3), MIB-1 and CD68, and negative for α-SMA, S-100, CD34 and myogenin. Thus, the tumour was diagnosed as high-grade MFS of the spermatic cord. Postoperative CT revealed a right renal tumour and adrenal tumour. Right radial nephrectomy was performed and the patient was doing well at 10-month follow-up.

  11. Modeling platinum sensitive and resistant high grade serous ovarian cancer: development and applications of experimental systems

    Directory of Open Access Journals (Sweden)

    Paula eCunnea


    Full Text Available High grade serous ovarian cancer remains the most common sub-type of ovarian cancer and, characterized by high degrees of genomic instability and heterogeneity, is typified by a transition from early response to acquired resistance to platinum based chemotherapy. Conventional models for the study of ovarian cancer have been largely limited to a set of relatively poorly characterized immortalized cell lines and recent studies have called into question the validity of some of these as reliable models. Here we review new approaches and models systems which take into account advances in our understanding of ovarian cancer biology and advances in the technology available for their generation and study. We discuss primary cell models, 2D, 3D and organotypic models, and paired sample approaches that capture the evolution of chemotherapy failure within single cases. We also overview new methods for non-invasive collection of representative tumor material from blood samples. Adoption of such methods and models will improve the quality and clinical relevance of ovarian cancer research.

  12. High-grade microscopic hematuria in adult men can predict urothelial malignancy. (United States)

    Kotb, Ahmed Fouad; Attia, Doaa


    Microscopic hematuria in men younger than 40 is a confusing issue to urologists, especially when these men have normal radiological findings. We report our experience in looking for urologic malignancy in this group of patients. We conducted a prospective study for men with vague urological symptoms. We included men under 40 years old, men with microscopic hematuria greater than 25 red blood cells/high power field in 2 properly collected mid-stream urine samples, and men with free urine culture and normal multiphasic computed tomography abdomen and pelvis studies. All patients underwent diagnostic cystoscurethroscopy. If there were no lesions, multiple random biopsies were taken. In cases of apparently normal cystoscopic findings and associated renal colic, uretroscopy was done to the suspected side. Only 20 patients fulfilled our inclusion criteria. The mean age of the patients were 34; 2 patients presented with pain. The other 18 patients were presenting with mild recurrent lower urinary tract symptoms. Cystoscopy showed small papillary low-grade tumour in 3 patients. All random biopsies were free of malignancy. Unilateral uretroscopy for the 2 cases presented with pain detected carcinoma in situ in one of them. Cystoscopy is highly recommended for young adult men, with significant levels of microscopic hematuria, due to the 20% incidence rate of associated urological malignancy. Random bladder biopsies, in the absence of suspicious lesions, have no diagnostic role, and should not be done. Uretroscopy is advised for patients with microscopic hematuria and loin pain, even in the absence of suspicious radiological findings.

  13. Efficient molecular subtype classification of high-grade serous ovarian cancer. (United States)

    Leong, Huei San; Galletta, Laura; Etemadmoghadam, Dariush; George, Joshy; Köbel, Martin; Ramus, Susan J; Bowtell, David


    High-grade serous carcinomas (HGSCs) account for approximately 70% of all epithelial ovarian cancers diagnosed. Using microarray gene expression profiling, we previously identified four molecular subtypes of HGSC: C1 (mesenchymal), C2 (immunoreactive), C4 (differentiated), and C5 (proliferative), which correlate with patient survival and have distinct biological features. Here, we describe molecular classification of HGSC based on a limited number of genes to allow cost-effective and high-throughput subtype analysis. We determined a minimal signature for accurate classification, including 39 differentially expressed and nine control genes from microarray experiments. Taqman-based (low-density arrays and Fluidigm), fluorescent oligonucleotides (Nanostring), and targeted RNA sequencing (Illumina) assays were then compared for their ability to correctly classify fresh and formalin-fixed, paraffin-embedded samples. All platforms achieved > 90% classification accuracy with RNA from fresh frozen samples. The Illumina and Nanostring assays were superior with fixed material. We found that the C1, C2, and C4 molecular subtypes were largely consistent across multiple surgical deposits from individual chemo-naive patients. In contrast, we observed substantial subtype heterogeneity in patients whose primary ovarian sample was classified as C5. The development of an efficient molecular classifier of HGSC should enable further biological characterization of molecular subtypes and the development of targeted clinical trials. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  14. Frequent EGFR Positivity and Overexpression in High-Grade Areas of Human MPNSTs

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    Séverine Tabone-Eglinger


    Full Text Available Malignant peripheral nerve sheath tumours (MPNSTs are highly malignant and resistant. Transformation might implicate up regulation of epidermal growth factor receptor (EGFR. Fifty-two MPNST samples were studied for EGFR, Ki-67, p53, and survivin expression by immunohistochemistry and for EGFR amplification by in situ hybridization. Results were correlated with clinical data. EGFR RNA was also quantified by RT-PCR in 20 other MPNSTs and 14 dermal neurofibromas. Half of the patients had a neurofibromatosis type 1 (NF1. EGFR expression, detected in 86% of MPNSTs, was more frequent in NF1 specimens and closely associated with high-grade and p53-positive areas. MPNSTs expressed more EGFR transcripts than neurofibromas. No amplification of EGFR locus was observed. NF1 status was the only prognostic factor in multivariate analysis, with median survivals of 18 and 43 months for patients with or without NF1. Finally, EGFR might become a new target for MPNSTs treatment, especially in NF1-associated MPNSTs.

  15. The Potential of Targeting Ribosome Biogenesis in High-Grade Serous Ovarian Cancer

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    Shunfei Yan


    Full Text Available Overall survival for patients with ovarian cancer (OC has shown little improvement for decades meaning new therapeutic options are critical. OC comprises multiple histological subtypes, of which the most common and aggressive subtype is high-grade serous ovarian cancer (HGSOC. HGSOC is characterized by genomic structural variations with relatively few recurrent somatic mutations or dominantly acting oncogenes that can be targeted for the development of novel therapies. However, deregulation of pathways controlling homologous recombination (HR and ribosome biogenesis has been observed in a high proportion of HGSOC, raising the possibility that targeting these basic cellular processes may provide improved patient outcomes. The poly (ADP-ribose polymerase (PARP inhibitor olaparib has been approved to treat women with defects in HR due to germline BRCA mutations. Recent evidence demonstrated the efficacy of targeting ribosome biogenesis with the specific inhibitor of ribosomal RNA synthesis, CX-5461 in v-myc avian myelocytomatosis viral oncogene homolog (MYC-driven haematological and prostate cancers. CX-5461 has now progressed to a phase I clinical trial in patients with haematological malignancies and phase I/II trial in breast cancer. Here we review the currently available targeted therapies for HGSOC and discuss the potential of targeting ribosome biogenesis as a novel therapeutic approach against HGSOC.

  16. Highly mobile ferroelastic domain walls in compositionally graded ferroelectric thin films. (United States)

    Agar, J C; Damodaran, A R; Okatan, M B; Kacher, J; Gammer, C; Vasudevan, R K; Pandya, S; Dedon, L R; Mangalam, R V K; Velarde, G A; Jesse, S; Balke, N; Minor, A M; Kalinin, S V; Martin, L W