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Sample records for alk1-negative anaplastic large

  1. Anaplastic Large Cell Lymphoma

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    Anaplastic Large Cell Lymphoma Overview Lymphoma is the most common blood cancer. The two main forms of lymphoma are ... organs, and can accumulate to form tumors. Anaplastic large cell lymphoma (ALCL) is arare type of NHL, ...

  2. Pathobiology of Anaplastic Large Cell Lymphoma

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    Pier Paolo Piccaluga

    2010-01-01

    Full Text Available The authors revise the concept of anaplastic large cell lymphoma (ALCL in the light of the recently updated WHO classification of Tumors of Hematopoietic and Lymphoid Tissues both on biological and clinical grounds. The main histological findings are illustrated with special reference to the cytological spectrum that is indeed characteristic of the tumor. The phenotype is reported in detail: the expression of the ALK protein as well as the chromosomal abnormalities is discussed with their potential pathogenetic implications. The clinical features of ALCL are presented by underlining the difference in terms of response to therapy and survival between the ALK-positive and ALK-negative forms. Finally, the biological rationale for potential innovative targeted therapies is presented.

  3. Research progresses in the pathogenesis of anaplastic large cell lymphoma

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    Xiao-Lan Shi; Xiao-Wen Tang; De-Pei Wu

    2011-01-01

    Anaplastic large cell lymphoma (ALCL) is a distinct subset of T-cell non-Hodgkin's lymphoma. As a consequence of its low incidence, general pathogenic consideration of ALCL is lacking. In this review, we summarize the pathogenesis, epidemiology, clinical manifestations, and treatment of ALCL, so as to better understand key stages of the development of this disease and provide valuable information for future treatment.

  4. Anaplastic large cell lymphoma: A single institution experience from India

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    K C Lakshmaiah

    2013-01-01

    Full Text Available Background: Systemic anaplastic large cell lymphoma (ALCL accounts for 2-8% of non-Hodgkin′s lymphoma in adults and 10-15% in children. While there is ample data in the world literature about the clinical features and outcome of this disease, prognosis in Indian patients is largely unknown. Objective: To study the clinical, pathologic profile and outcome ALCL. Materials and Methods: Fifty patients who had pathologically proven diagnosis of systemic ALCL at our institute from June 2003 to May 2011 were included for retrospective analysis. This included 30 cases of anaplastic lymphoma kinase+ (ALK+, ALCL and 20 cases of anaplastic lymphoma kinase- (ALK−, ALCL. The hospital protocol for treatment of these patients included CHOP chemotherapy regimen in >15 years of age and MCP842 protocol with vinblastine for 1 year in <15 years of age. Event free survival was noted. These outcomes were correlated with ALK status, International Prognostic Index (IPI score, and stage at presentation. Results: At a median follow-up of 36 months (range: 6-72 months ALK− ALCL had a poor outcome. The 3 year event free survival in pediatric ALCL was 66.7%. In adults, this was 60% ALK+ ALCL was 60% and 20% in ALK− ALCL. Conclusions: Systemic ALCL is an aggressive disease. CD3 + positivity is commonly seen in ALK− ALCL and ALK+, epithelial membrane antigen + positivity is seen in ALK+ ALCL. ALK− ALCL, advanced stage III, IV and high IPI score were associated with poor prognosis. The demographic profile and outcome in our study was similar to the world literature. With new drugs like crizotinib and brentuximab vedotin the future looks very promising.

  5. ALK signaling and target therapy in anaplastic large cell lymphoma

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    Fabrizio eTabbo

    2012-05-01

    Full Text Available The discovery by Morris SW et al. in 1994 of the genes contributing to the t(2;5(p23;q35 translocation has put the foundation for a molecular based recognition of Anaplastic Large Cell Lymphoma (ALCL and pointed out the need for a further stratification of T-cell neoplasia. Likewise the detection of ALK genetic lesions among many human cancers has defined unique subsets of cancer patients, providing new opportunities for innovative therapeutic interventions. The objective of this review is to appraise the molecular mechanisms driving ALK-mediated transformation, and to maintain the neoplastic phenotype. The understanding of these events will allow the design and implementation of novel tailored strategies for a well-defined subset of cancer patients.

  6. Primary cutaneous anaplastic large-cell lymphoma: a case report.

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    Cao, Can; Zeng, Kang; Wang, Menglei; Han, Kai; Peng, Yusheng; Xiong, Hao; Wang, Qi; Li, Qian; Wang, Qian; Li, Li

    2016-07-01

    Primary cutaneous anaplastic large-cell lymphoma (PCALCL) is a part of the spectrum of CD30+ lymphoproliferative cutaneous processes. The characteristics include single or multifocal nodules that ulcerate as skin lesion, slow disease progression, autoregressive, and recurrent in few years. The present study report the case of a 16-year-old boy presenting PCALCL with single nodules, ulcer, keloid, and scab in his right-side face. He showed a good response to the treatment with systemic chemotherapy and dermatoplasty, and regained confidence after the appearance of recovery. There is no relapse of the primary lesion and organs involved till now. The chemotherapy combining with surgical excision and dermatoplasty is a good method for PCALCL, per the lesion biopsy and positron emission tomography-computed tomography before and after treatment. PMID:26970422

  7. MicroRNA Expression Profiling Identifies Molecular Diagnostic Signatures for Anaplastic Large Cell Lymphoma

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    Liu, Cuiling; Iqbal, Javeed; Teruya-Feldstein, Julie;

    2013-01-01

    Anaplastic large-cell lymphomas (ALCLs) encompass at least 2 systemic diseases distinguished by the presence or absence of anaplastic lymphoma kinase (ALK) expression. We performed genome-wide microRNA (miRNA) profiling on 33 ALK-positive (ALK[+]) ALCLs, 25 ALK-negative (ALK[-]) ALCLs, 9 angioimm...

  8. Anaplastic lymphoma kinase negative anaplastic large cell lymphoma of hard palate as first clinical manifestation of acquired immune deficiency syndrome.

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    Narwal, Anjali; Yadav, Achla Bharti; Prakash, Sant; Gupta, Shally

    2016-01-01

    Anaplastic large cell lymphoma (ALCL) is an uncommon disease, accounting for <5% of all cases of non-Hodgkin's lymphoma. We report a case of 48-year-old male who presented a clinically benign swelling in the right anterior palatal region since last 2 months. Radiographic evaluation showed no bone loss in palatal area. Histological and radiological examination was in favor of a peripheral reactive lesion like pyogenic granuloma or a benign salivary gland tumor. Immunohistochemistry confirmed the diagnosis of anaplastic lymphoma kinase-negative (ALK(-)) ALCL. Further laboratory tests ELISA for human immunodeficiency virus (HIV) and CD4 cell count was done which showed positivity for HIV. To the best of our knowledge, it is the first case of ALK(-) ALCL in the hard palate presenting as the first clinical manifestation of acquired immune deficiency syndrome. PMID:27041916

  9. Anaplastic lymphoma kinase negative anaplastic large cell lymphoma of hard palate as first clinical manifestation of acquired immune deficiency syndrome

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    Anjali Narwal

    2016-01-01

    Full Text Available Anaplastic large cell lymphoma (ALCL is an uncommon disease, accounting for <5% of all cases of non-Hodgkin's lymphoma. We report a case of 48-year-old male who presented a clinically benign swelling in the right anterior palatal region since last 2 months. Radiographic evaluation showed no bone loss in palatal area. Histological and radiological examination was in favor of a peripheral reactive lesion like pyogenic granuloma or a benign salivary gland tumor. Immunohistochemistry confirmed the diagnosis of anaplastic lymphoma kinase-negative (ALK(− ALCL. Further laboratory tests ELISA for human immunodeficiency virus (HIV and CD4 cell count was done which showed positivity for HIV. To the best of our knowledge, it is the first case of ALK(− ALCL in the hard palate presenting as the first clinical manifestation of acquired immune deficiency syndrome.

  10. Association of Systemic Anaplastic Large Cell Lymphoma and Active Toxoplasmosis in a Child

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    Sayyahfar, Shirin; Karimi, Abdollah; Gharib, Atoosa; Fahimzad, Alireza

    2015-01-01

    Introduction: Anaplastic large cell lymphoma is a subset of non-Hodgkin lymphoma and an unusual disease in children. Case Presentation: Herein we have reported a 7- year- old girl with a large necrotic skin ulcer on the chest caused by systemic form of anaplastic large-cell lymphoma and simultaneous active toxoplasmosis diagnosed by PCR on lymph node specimen. There were few reports showing a role for toxoplasma infection to cause some malignancies such as lymphoma in adults. Conclusions: Bas...

  11. Neutrophil rich anaplastic large cell lymphoma presented as cutaneous nodules in an adolescent

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ Anaplastic large cell lymphoma (ALCL),a type of lymphoma,was first described by Stain in 1985 and included in non-Hodgkin lymphoma according to REAL classification since 1998.In the absence of necrosis,neutrophils infiltration in non-Hodgkin lymphoma is uncommon.Mann et all had previously reported neutrophil rich ALCL as a variant of ALCL.In this paper,we describe a neutrophil rich,anaplastic large cell lymphoma (ALCL) which presented as cutaneous nodules in an adolescent.

  12. Cardiac anaplastic large cell lymphoma in an 8-year old boy

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    Melchior Lauten

    2014-01-01

    Full Text Available We report on an 8 year old boy with primary cardiac anaplastic large cell lymphoma (ALCL, in whom the diagnosis was challenging and who was treated with modified chemotherapy without radiation therapy according to the ALCL 99 study protocol [1]. Two years and 4 months after completion of therapy the boy is in complete remission with normal cardiac function.

  13. Cardiac anaplastic large cell lymphoma in an 8-year old boy

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    Melchior Lauten; Simon Vieth; Christopher Hart; Wilhelm Wössmann; Birte Tröger; Christoph Härtel; Martin Bethge; André Schrauder; Gunnar Cario

    2014-01-01

    We report on an 8 year old boy with primary cardiac anaplastic large cell lymphoma (ALCL), in whom the diagnosis was challenging and who was treated with modified chemotherapy without radiation therapy according to the ALCL 99 study protocol [1]. Two years and 4 months after completion of therapy the boy is in complete remission with normal cardiac function.

  14. Large cell anaplastic medulloblastoma metastatic to the scalp: tumor and derived stem-like cells features

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    Mastronuzzi, Angela; Miele, Evelina; Po, Agnese; Antonelli, Manila; Buttarelli, Francesca Romana; Colafati, Giovanna Stefania; Del Bufalo, Francesca; Faedda, Roberta; Spinelli, Gian Paolo; Carai, Andrea; Giangaspero, Felice; Gulino, Alberto; Locatelli, Franco; Ferretti, Elisabetta

    2014-01-01

    Background Extraneural metastases (ENM) rarely occur in medulloblastoma (MBL) patients and only few cases of subcutaneous localizations have been described. ENM indicate an aggressive disease associated with a worse prognosis. The characterization of metastatic tumours might be useful to understand their pathogenesis and to identify the most appropriate therapeutic strategies. Case presentation We present the case of a child with Large Cell Anaplastic (LC/A) MBL, who developed multiple subcut...

  15. ALK-positive anaplastic large cell lymphoma with soft tissue involvement in a young woman

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    Gao KH

    2016-07-01

    Full Text Available Kehai Gao, Hongtao Li, Caihong Huang, Huazhuang Li, Jun Fang, Chen Tian Department of Orthopaedics, Yidu Central Hospital, Shandong, People’s Republic of China Introduction: Anaplastic large cell lymphoma (ALCL is a type of non-Hodgkin lymphoma that has strong expression of CD30. ALCL can sometimes involve the bone marrow, and in advanced stages, it can produce destructive extranodal lesions. But anaplastic large cell lymphoma kinase (ALK+ ALCL with soft tissue involvement is very rare.Case report: A 35-year-old woman presented with waist pain for over 1 month. The biopsy of soft tissue lesions showed that these cells were positive for ALK-1, CD30, TIA-1, GranzymeB, CD4, CD8, and Ki67 (90%+ and negative for CD3, CD5, CD20, CD10, cytokeratin (CK, TdT, HMB-45, epithelial membrane antigen (EMA, and pan-CK, which identified ALCL. After six cycles of Hyper-CVAD/MA regimen, she achieved partial remission. Three months later, she died due to disease progression.Conclusion: This case illustrates the unusual presentation of ALCL in soft tissue with a bad response to chemotherapy. Because of the tendency for rapid progression, ALCL in young adults with extranodal lesions are often treated with high-grade chemotherapy, such as Hyper-CVAD/MA. Keywords: anaplastic large cell lymphoma, ALK+, soft tissue involvement, Hyper-CVAD/MA

  16. A rare case of ALK negative CD30+ primary cutaneous anaplastic large cell lymphoma in a young adult

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    H B Sridevi

    2015-01-01

    Full Text Available Cutaneous anaplastic large cell lymphoma can present either as a primary disease or as secondary to a pre-existing systemic anaplastic lymphoma. Distinguishing primary cutaneous anaplastic lymphoma (PC-ALCL from its systemic counterpart requires a complete clinical and laboratory workup. We hereby report a case of PC-ALCL in a young adult, who presented with unusual rapidly progressive ulcerated mass in the neck. Biopsy showed anaplastic large cells, which were strongly positive for CD30 and CD25 but ALK1 gene product was negative. Clinical examination and computed tomography (CT scan ruled out extracutaneous involvement. Chemotherapy with 6 cycles of CHOP regimen was planned and on follow-up, a complete remission of the lesion was attained.

  17. CD30-Positive Anaplastic Lymphoma Kinase-Negative Systemic Anaplastic Large-Cell Lymphoma in a 9-Year-Old Boy

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    Kim, Jeong Eun; Oh, Eui Hyun; Ro, Young Suck

    2016-01-01

    Anaplastic large-cell lymphoma (ALCL) is a CD30-positive T-cell/null-cell lymphoma that is clinically classified into either primary cutaneous ALCL or systemic ALCL (S-ALCL) sub-types. Because 90% of childhood S-ALCL cases are anaplastic lymphoma kinase (ALK)-positive, there is a lack of data on ALK-negative S-ALCL cases among pediatric patients. Herein, we report a rare case of ALK-negative S-ALCL in a 9-year-old Korean boy who initially presented with itchy erythematous maculopapules and an erosive nodule on the trunk area. We emphasize the need of high index of suspicion of an underlying malignant disease in the presence of refractory eczematous lesions. PMID:27274637

  18. Indium-111-oxine labeled leukocyte uptake in Ki-1-positive anaplastic large cell lymphoma

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    Chiu, W.; Amodio, J.B.; Scharf, S.C. (New York Univ., NY (United States). Dept. of Radiology); Rivlin, K.A. (Department of Hematology and Oncology, New York Univ. Medical Center, NY (United States)); Desai, P. (Department of Pathology, Hospital for Joint Diseases-Orthopaedic Inst., New York, NY (United States)); Breuer, F. (Department of Pathology, Lenox Hill Hospital, New York, NY (United States))

    1999-08-01

    Indium-111-oxine labeled leukocyte ([sup 111]In-WBC) scintigraphy is well known for its ability to localize in areas of active infection, but not in areas of lymphomatous involvement. We present a case of Ki-1-positive anaplastic large-cell lymphoma that was initially thought to be a case of multifocal osteomyelitis because of positive uptake on a [sup 111]In-WBC scan. The areas of abnormal uptake on the indium scan were demonstrated histopathologically to be sites of lymphomatous involvement in bone. (orig.) With 4 figs., 3 refs.

  19. Indium-111-oxine labeled leukocyte uptake in Ki-1-positive anaplastic large cell lymphoma

    International Nuclear Information System (INIS)

    Indium-111-oxine labeled leukocyte (111In-WBC) scintigraphy is well known for its ability to localize in areas of active infection, but not in areas of lymphomatous involvement. We present a case of Ki-1-positive anaplastic large-cell lymphoma that was initially thought to be a case of multifocal osteomyelitis because of positive uptake on a 111In-WBC scan. The areas of abnormal uptake on the indium scan were demonstrated histopathologically to be sites of lymphomatous involvement in bone. (orig.)

  20. Combination therapy with brentuximab vedotin and cisplatin/cytarabine in a patient with primarily refractory anaplastic lymphoma kinase positive anaplastic large cell lymphoma

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    Heidegger S

    2014-06-01

    Full Text Available Simon Heidegger,1 Ambros Beer,2 Eva Geissinger,3 Andreas Rosenwald,3 Christian Peschel,1 Ingo Ringshausen,1 Ulrich Keller11III Medical Department, 2Nuclear Medicine Department, Technische Universität München, Munich, Germany; 3Institute of Pathology, University of Würzburg, Würzburg, GermanyAbstract: Anaplastic large cell lymphoma (ALCL is a common subtype of the heterogeneous group of peripheral T-cell lymphomas, which is characterized by large pleomorphic cells with strong expression of CD30. Translocations involving ALK, the anaplastic lymphoma kinase gene, are associated with a favorable clinical outcome. Such ALK-positive ALCLs are usually responsive to a multidrug chemotherapy with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone. However, there is no general consensus on the optimal therapy for relapsed or refractory ALCL. We report the case of a 24-year-old male suffering from ALK-positive ALCL with an uncommon manifestation of only extranodal disease in the gastric cardia region that showed primary refractoriness to standard CHOP chemotherapy. A combination therapy consisting of the anti-CD30 drug conjugate, brentuximab vedotin, and classical lymphoma salvage regimen DHAP (cisplatin, high-dose cytarabine and dexamethasone was administered. Following two treatment cycles in 21-day intervals, the lymphoma showed considerable regression based on imaging diagnostics and no evidence of vital lymphoma in a subsequent biopsy. We did not observe any increase in toxicity; in particular, polyneuropathy and febrile neutropenia were not observed. In summary, we report that the antibody-drug conjugate brentuximab vedotin and a classical regimen used for aggressive lymphoma, DHAP, could be combined as salvage therapy in a case of refractory ALK-positive ALCL. Phase I/II studies will be required for safety and efficacy analysis.Keywords: anaplastic large cell lymphoma (ALCL, refractory/relapsed lymphoma, anti-CD30 drug conjugate, DHAP

  1. Targeted therapy for Hodgkin lymphoma and systemic anaplastic large cell lymphoma: focus on brentuximab vedotin

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    Chen X

    2013-12-01

    Full Text Available Xueyan Chen, Lorinda A Soma, Jonathan R FrommDepartment of Laboratory Medicine, University of Washington Medical Center, Seattle, WA, USAAbstract: Despite the relative success of chemotherapy for Hodgkin lymphoma (HL and systemic anaplastic large cell lymphoma (ALCL, novel therapeutic agents are needed for refractory or relapsed patients. Targeted immunotherapy has emerged as a novel treatment option for these patients. Although unconjugated anti-cluster of differentiation (CD30 antibodies showed minimal antitumor activity in early clinical trials, development of antibody–drug conjugates (ADCs appears promising. Brentuximab vedotin is an ADC composed of an anti-CD30 antibody linked to a potent microtubule-disrupting agent monomethyl auristatin E (MMAE. It has the ability to target CD30-positive tumor cells and, once bound to CD30, brentuximab vedotin is internalized and MMAE is released to induce cell cycle arrest and apoptosis. In two phase II trials, objective response was reported in 75% and 86% of patients with refractory or relapsed HL and systemic ALCL, respectively, with an acceptable toxicity profile. Based on these studies, the US Food and Drug Administration (FDA granted accelerated approval of brentuximab vedotin in August 2011 for the treatment of refractory and relapsed HL and ALCL. We review the key characteristics of brentuximab vedotin, clinical data supporting its therapeutic efficacy, and current ongoing trials to explore its utility in other CD30-positive malignancies.Keywords: classical Hodgkin lymphoma, systemic anaplastic large cell lymphoma, CD30, brentuximab vedotin, SGN-35

  2. Clinical features and treatment results in children with anaplastic large cell lymphoma.

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    Ataş, Erman; Kutluk, M Tezer; Akyüz, Canan; Kale, Gülsev; Varan, Ali; Yalçın, Bilgehan; Aydın, Burça; Büyükpamukçu, Münevver

    2015-01-01

    Anaplastic large cell lymphoma (ALCL) tends to have frequent relapse and good response to salvage chemotherapy. The frequency of ALCL among 1486 Non-Hodgkin's lymphoma (NHL) cases followed-up since 1972 was 1.5%, however, the percentage was 9.3% in cases diagnosed after 2000. Event-free survival (EFS) and overall survival (OS) rates for 23 children were 32.2% and 72.8% at 3 years, respectively. Disseminated diseases, no response to first line treatment, anaplastic lymphoma kinase (ALK) negativity were found as significant predictors on survival of ALCL. The proper diagnosis and early referral is essential in these children for a better survival rate. The children with ALK negative status should be monitored carefully because of the poor prognostic factors, and treated differently. The survival rates in this study are need of further improvement since the survival rates with current protocols are achievable at a level more than 80%. This is mainly related with late referral of those children with advanced disease. PMID:27411412

  3. A novel Patient Derived Tumorgraft model with TRAF1-ALK Anaplastic Large Cell Lymphoma translocation

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    Abate, Francesco; Todaro, Maria; van der Krogt, Jo-Anne; Boi, Michela; Landra, Indira; Machiorlatti, Rodolfo; Tabbo’, Fabrizio; Messana, Katia; Barreca, Antonella; Novero, Domenico; Gaudiano, Marcello; Aliberti, Sabrina; Di Giacomo, Filomena; Tousseyn, Thomas; Lasorsa, Elena; Crescenzo, Ramona; Bessone, Luca; Ficarra, Elisa; Acquaviva, Andrea; Rinaldi, Andrea; Ponzoni, Maurilio; Longo, Dario Livio; Aime, Silvio; Cheng, Mangeng; Ruggeri, Bruce; Piccaluga, Pier Paolo; Pileri, Stefano; Tiacci, Enrico; Falini, Brunangelo; Pera-Gresely, Benet; Cerchietti, Leandro; Iqbal, Javeed; Chan, Wing C; Shultz, Leonard D.; Kwee, Ivo; Piva, Roberto; Wlodarska, Iwona; Rabadan, Raul; Bertoni, Francesco; Inghirami, Giorgio

    2016-01-01

    Although Anaplastic Large Cell Lymphomas (ALCL) carrying Anaplastic Lymphoma Kinase (ALK) have a relatively good prognosis, aggressive forms exist. We have identified a novel translocation, causing the fusion of the TRAF1 and ALK genes, in one patient who presented with a leukemic ALK+ ALCL (ALCL-11). To uncover the mechanisms leading to high-grade ALCL, we developed a human Patient Derived Tumorgraft (hPDT) line. Molecular characterization of primary and PDT cells demonstrated the activation of ALK and of NFkB pathways. Genomic studies of ALCL-11 showed the TP53 loss and the in vivo subclonal expansion of lymphoma cells lacking PRDM1/Blimp-1 and with c-MYC gene amplification. The treatment with proteasome inhibitors of TRAF1-ALK cells led to down-regulation of p50/p52 and lymphoma growth inhibition. Moreover a NFkB gene set classifier stratified ALCL in distinct subsets with different clinical outcome. Moreover, a selective ALK inhibitor (CEP28122) resulted in a significant clinical response of hPDT mice, but the disease could not be eradicated. These data indicate that the activation of NFkB signaling contributes to the neoplastic phenotype of TRAF1-ALK ALCL. ALCL hPDTs are invaluable to validate the role of druggable molecules, predict therapeutic responses and are helpful tools for the implementation of patient specific therapies. PMID:25533804

  4. Detection of an early adult T-cell leukemia-lymphoma clone in lymph nodes with anaplastic lymphoma kinase-negative anaplastic large cell lymphoma involvement.

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    Tokunaga, Masahito; Yoshida, Noriaki; Nakano, Nobuaki; Kubota, Ayumu; Takeuchi, Shogo; Takatsuka, Yoshifusa; Seto, Masao; Utsunomiya, Atae

    2016-04-01

    A 58-year-old man was admitted to our hospital with systemic lymphadenopathy and was diagnosed with anaplastic lymphoma kinase-negative anaplastic large cell lymphoma (ALCL) by lymph node biopsy. Although he was a human T-cell leukemia virus type I (HTLV-1) carrier, Southern blot analysis of the lymph node did not show monoclonal integration of HTLV-1 provirus deoxyribonucleic acid (DNA). He achieved complete remission after chemotherapy and subsequently, autologous peripheral blood stem cell transplantation (auto-PBSCT) was performed. Fifteen months after the auto-PBSCT, abnormal lymphocytes in the peripheral blood gradually increased. Southern blot analysis revealed monoclonal integration of HTLV-1 provirus DNA and monoclonal rearrangement of TRB. He was diagnosed with chronic type adult T-cell leukemia-lymphoma (ATL), which immediately progressed to the acute type. He died of tumor progression despite intensive chemotherapy. We analyzed genomic alterations of the ALCL and ATL cells using array comparative genomic hybridization. We found that the genomic alteration pattern differed between the two diseases. T-cell receptor clonality analysis using polymerase chain reaction (PCR) showed that the T-cell clone of the ATL was present in the lymph nodes with ALCL involvement, but not in peripheral blood. This finding suggests that lymph nodes can serve as a niche for ATL development. PMID:26874918

  5. A Report of a Rare Case of Anaplastic Large Cell Lymphoma of the Oral Cavity

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    Prasad G Kango

    2012-01-01

    Full Text Available Case history: Malignant lymphoma is a neoplastic proliferative process of the lymphopoietic portion of the reticuloendothelial system that involves cells of either the lymphocytic or histiocytic series in varying degrees of differentiation and occurs in an essentially homogenous population of a single cell type. The character of histologic involvement is either diffuse (uniform or nodular and the distribution of involvement may be regional or systemic (generalized, the process basically being multicentric. A case of oral cavity lymphoma was detected and after various panel of imunnohistochemical (IHC markers it was diagnosed as Anaplastic large cell lymphomas (ALCL of oral cavity. Conclusion: Lymphoma of oral regions are very rare and ALCL is rarest. It is of utmost importance to do the IHC, so that the prognosis of the lesion is known at the earliest. In this case since it was detected at a later stage the outcome was fatal.

  6. Synchronous Occurrence of Primary Cutaneous Anaplastic Large Cell Lymphoma and Squamous Cell Carcinoma

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    Park, Ji-Hye; Lee, Jae Ho; Lim, Youngkyoung; Lee, You Jin

    2016-01-01

    CD30+ lymphoproliferative disorders (LPD) represent a spectrum of T-cell lymphoma including lymphomatoid papulosis and anaplastic large cell lymphoma (ALCL). Epidermis overlying cutaneous CD30+ LPD often shows epidermal hyperplasia, hyperkeratosis, crusting, and ulceration and it is difficult to distinguish from carcinoma such as keratoacanthoma (KA) or squamous cell carcinoma (SCC). Several cases of pseudocarcinomatous hyperplasia mimicking KA or SCC in CD30+ LPD have been reported. The relationship between CD30+ LPD and epithelial proliferations has not yet well understood. It was reported that a variety of mediators, including epidermal growth factor (EGF), transforming growth factor-α and EGFR from CD30+ LPD could attribute to epidermal hyperplasia. However, separate and distinct SCC occurring in CD30+ LPD has rarely been reported. Herein, we present a rare case of coexistence of SCC and cutaneous ALCL located on the same region. PMID:27489433

  7. Primary pancreatic anaplastic large cell lymphoma, ALK negative:A case report

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    Christos G Savopoulos; NE Tsesmeli; GD Kaiafa; AT Zantidis; MT Bobos; AI Hatzitolios; ST Papavramidis; IS Kostopoulos

    2005-01-01

    We present the fourth case of a primary pancreatic anaplastic large cell lymphoma (ALCL), ALK-. An 80-year-old man was admitted to our clinic for further investigation of a fever of unknown origin. He noted anorexia, weight loss and fatigue. His laboratory tests showed anemia and a great elevation of ESR, LDH, and β2 microglobulin. In CT and MRI scan, a soft tissue mass in the pancreas was observed. A repeated endoscopy after his admission revealed an ulcerated mass-like deformity of the duodenal bulb. Explorative laparotomy confirmed a diffuse spread of an unresectable malignant pancreatic mass extending to the adjacent organs. Duodenal and surgical biopsies identified an ALCL of T-cell lineage, ALK-. The patient died in the Intensive Care Unit due to hemodynamic instability.Our case is the first one indicating that primary pancreatic lymphoma should be suspected in a patient with pancreatic mass and elevated serum LDH and β2 microglobulin.

  8. Isolated cutaneous involvement in a child with nodal anaplastic large cell lymphoma

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    Vibhu Mendiratta

    2016-01-01

    Full Text Available Non-Hodgkin lymphoma is a common childhood T-cell and B-cell neoplasm that originates primarily from lymphoid tissue. Cutaneous involvement can be in the form of a primary extranodal lymphoma, or secondary to metastasis from a non-cutaneous location. The latter is uncommon, and isolated cutaneous involvement is rarely reported. We report a case of isolated secondary cutaneous involvement from nodal anaplastic large cell lymphoma (CD30 + and ALK + in a 7-year-old boy who was on chemotherapy. This case is reported for its unusual clinical presentation as an acute febrile, generalized papulonodular eruption that mimicked deep fungal infection, with the absence of other foci of systemic metastasis.

  9. Anaplastic large cell lymphoma ALK-negative clinically mimicking alcoholic hepatitis – a review

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    Fernando Peixoto Ferraz de Campos

    2013-10-01

    Full Text Available Anaplastic large cell lymphoma (ALCL, described less than 30 years ago by Karl Lennert and Herald Stein in Kiel, West Germany, is a T-cell or null non-Hodgkin lymphoma, with distinctive morphology (hallmark cells, prominent sinus and/or perivascular growth pattern, characteristic immunophenotype (CD30+, cytotoxic granules protein+, CD3–/+ and specific genetic features as translocations involving the receptor tyrosine kinase called anaplastic lymphoma kinase (ALK on 2p23 and variable partners genes, which results in the expression of ALK fusion protein. The absence of ALK expression is also observed and is associated with poorer prognosis that seen with ALK expression. ALK-negative ALCL is more frequent in adults, with both nodal and extra nodal clinical presentation and includes several differential diagnoses with other CD30+ lymphomas. Liver involvement by ALCL is rare and is generally seen as mass formation; the diffuse pattern of infiltration is even more unusual. The authors present a case of a 72-year-old man who presented clinical symptoms of acute hepatic failure. The patient had a long history of alcohol abuse and the diagnosis of alcoholic hepatitis was highly considered, although the serum lactic dehydrogenase (LDH value was highly elevated. The clinical course was fulminant leading to death on the fourth day of hospitalization. Autopsy demonstrated diffuse neoplastic hepatic infiltration as well as splenic, pulmonary, bone marrow, and minor abdominal lymph nodes involvement by the tumor. Based on morphological, immunophenotypical, and immunohistochemical features, a diagnosis of ALK- negative ALCL was concluded. When there is marked elevation of LDH the possibility of lymphoma, ALCL and other types, should be the principal diagnosis to be considered.

  10. Clinical and laboratory characteristics of systemic anaplastic large cell lymphoma in Chinese patients

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    Wang Yan-Fang

    2012-07-01

    Full Text Available Abstract Background Systemic anaplastic large cell lymphoma (S-ALCL is a rare disease with a highly variable prognosis and no standard chemotherapy regimen. Anaplastic lymphoma kinase (ALK has been reported as an important prognostic factor correlated with S-ALCL in many but not all studies. In our study, we retrospectively analyzed 92 patients with S-ALCL from the Peking University Lymphoma Center for clinical and molecular prognostic factors to make clear the role of ALK and other prognostic factors in Han Chinese S-ALCL. Results The majority of Chinese S-ALCL patients were young male patients (median age 26, male/female ratio 1.7 and the median age was younger than previous reports regardless of ALK expression status. The only statistically significant different clinical characteristic in S-ALCL between ALK positive (ALK+ and ALK negative (ALK- was age, with a younger median age of 22 for ALK+ compared with 30 for ALK-. However, when pediatric patients (≤18 were excluded, there was no age difference between ALK+ and ALK-. The groups did not differ in the proportion of males, those with clinical stage III/IV (49 vs 51% or those with extranodal disease (53 vs 59%. Of 73 evaluable patients, the 3-year and 5-year survival rates were 60% and 47%, respectively. Univariate analysis showed that three factors: advanced stage III/IV, lack of expression of ALK, and high Ki-67 expression, were associated with treatment failure in patients with S-ALCL. However, ALK expression correlated with improved survival only in patients younger than 14 years, while not in adult patients. In multivariate analysis, only clinical stage was an independent prognostic factor for survival. Expressions of Wilms tumor 1 (WT1 and B-cell lymphoma 2 protein (BCL-2 correlated with the expression of ALK, but they did not have prognostic significance. High Ki-67 expression was also a poor prognostic factor. Conclusions Our results show that ALK expression alone is not

  11. Three Years Sustained Complete Remission Achieved in a Primary Refractory ALK-Positive Anaplastic T Large Cell Lymphoma Treated with Crizotinib

    Science.gov (United States)

    Mahuad, Carolina Valeria; Repáraz, María de los Ángeles Vicente; Zerga, Marta E.; Aizpurua, María Florencia; Casali, Claudia; Garate, Gonzalo

    2016-01-01

    The prognosis of the primary refractory anaplastic lymphoma kinase (ALK+) anaplastic T large cell lymphoma is ominous. The identification of molecular targets with potential to drive oncogenesis remains a cornerstone for the designing of new selective cancer therapies. Crizotinib is a selective ATP-competitive inhibitor for ALK, approved for its use in lung cancer with rearrangements on ALK gene. The reported cases describe the use of crizotinib as a bridging strategy prior to allotransplantation; there are no reported prolonged survivals under monotherapy with Crizotinib. We report a case of a primary refractory ALK+ anaplastic large-cell lymphoma that sustains complete response after 3 years of crizotinib monotherapy.

  12. Three Years Sustained Complete Remission Achieved in a Primary Refractory ALK-Positive Anaplastic T Large Cell Lymphoma Treated with Crizotinib.

    Science.gov (United States)

    Mahuad, Carolina Valeria; Repáraz, María de Los Ángeles Vicente; Zerga, Marta E; Aizpurua, María Florencia; Casali, Claudia; Garate, Gonzalo

    2016-06-28

    The prognosis of the primary refractory anaplastic lymphoma kinase (ALK+) anaplastic T large cell lymphoma is ominous. The identification of molecular targets with potential to drive oncogenesis remains a cornerstone for the designing of new selective cancer therapies. Crizotinib is a selective ATP-competitive inhibitor for ALK, approved for its use in lung cancer with rearrangements on ALK gene. The reported cases describe the use of crizotinib as a bridging strategy prior to allotransplantation; there are no reported prolonged survivals under monotherapy with Crizotinib. We report a case of a primary refractory ALK+ anaplastic large-cell lymphoma that sustains complete response after 3 years of crizotinib monotherapy. PMID:27441079

  13. Successful treatment in a child with anaplastic large cell lymphoma and coexistence of pulmonary tuberculosis.

    Science.gov (United States)

    Baka, Margarita; Doganis, Dimitrios; Pourtsidis, Apostolos; Tsolia, Maria; Bouhoutsou, Despina; Varvoutsi, Maria; Strantzia, Katerina; Kosmidis, Helen

    2013-01-01

    A 13-year-old girl was admitted to our department with a history of severe pain of her left axilla and fever. On physical examination, a block of lymph nodes in her left axilla, diffuse papular rash, and red-violet swelling of her supraclavicular and subclavian region were noted. Imaging investigations revealed left axillar and supraclavicular lymphadenopathy and a small nodular shade in the upper lobe of her left lung. A biopsy from an axillary lymph node established the diagnosis of anaplastic large cell lymphoma (ALCL), whereas DNA of Mycobacterium tuberculosis was detected by polymerase chain reaction (PCR) in the same tissue biopsy. Patient was started on chemotherapy for ALCL and achieved remission of all initially involved fields. Nevertheless, two new nodular lesions were detected in the left lower lobe. Biopsy revealed granulomas, and PCR was positive for M. tuberculosis. Our patient received treatment with the combination of isoniazid and rifampin (12 months), pyrazinamide (the first 2 months), and maintenance chemotherapy for her ALCL for one year simultaneously. Four years later, she is disease free for both mycobacterial infection and lymphoma. We are reporting this successful management of mycobacterial infection in a patient with ALCL despite intensive chemotherapy that the patient received at the same time. PMID:23841007

  14. Successful Treatment in a Child with Anaplastic Large Cell Lymphoma and Coexistence of Pulmonary Tuberculosis

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    Margarita Baka

    2013-01-01

    Full Text Available A 13-year-old girl was admitted to our department with a history of severe pain of her left axilla and fever. On physical examination, a block of lymph nodes in her left axilla, diffuse papular rash, and red-violet swelling of her supraclavicular and subclavian region were noted. Imaging investigations revealed left axillar and supraclavicular lymphadenopathy and a small nodular shade in the upper lobe of her left lung. A biopsy from an axillary lymph node established the diagnosis of anaplastic large cell lymphoma (ALCL, whereas DNA of Mycobacterium tuberculosis was detected by polymerase chain reaction (PCR in the same tissue biopsy. Patient was started on chemotherapy for ALCL and achieved remission of all initially involved fields. Nevertheless, two new nodular lesions were detected in the left lower lobe. Biopsy revealed granulomas, and PCR was positive for M. tuberculosis. Our patient received treatment with the combination of isoniazid and rifampin (12 months, pyrazinamide (the first 2 months, and maintenance chemotherapy for her ALCL for one year simultaneously. Four years later, she is disease free for both mycobacterial infection and lymphoma. We are reporting this successful management of mycobacterial infection in a patient with ALCL despite intensive chemotherapy that the patient received at the same time.

  15. Infectious Mimicry Complicates Diagnosis in Hemophagocytic Syndrome Caused by Anaplastic Large-Cell Lymphoma

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    Michael J. Peluso

    2012-01-01

    Full Text Available Hemophagocytic syndrome (HPS arises secondary to genetic, rheumatologic, neoplastic, and infectious causes. We discuss a patient whose presentation was consistent with systemic infection but was discovered to have HPS of unknown etiology. The presenting symptoms, as well as unremarkable malignancy and rheumatologic workups, led to the pursuit of an infectious cause, but the patient was ultimately discovered to have an occult anaplastic large-cell lymphoma (ALCL. This case demonstrates the diagnostic challenges that result from infectious mimicry in the context of HPS—first, in distinguishing noninfectious HPS from the systemic inflammation that can result from a widespread infectious process, second, in the identification of the precipitating cause of HPS. While evidence of these challenges has been suggested by the limited literature on HPS and ALCL, our case illustrates the diagnostic dilemma that arises when tissue biopsy does not quickly reveal an etiology. It is important that all physicians be aware that HPS can mimic infection and be prepared to redirect the workup when an infectious etiology for HPS cannot be identified.

  16. Large cell anaplastic medulloblastoma metastatic to the scalp: tumor and derived stem-like cells features

    International Nuclear Information System (INIS)

    Extraneural metastases (ENM) rarely occur in medulloblastoma (MBL) patients and only few cases of subcutaneous localizations have been described. ENM indicate an aggressive disease associated with a worse prognosis. The characterization of metastatic tumours might be useful to understand their pathogenesis and to identify the most appropriate therapeutic strategies. We present the case of a child with Large Cell Anaplastic (LC/A) MBL, who developed multiple subcutaneous metastases in the scalp area after a ventriculo-peritoneal shunting procedure. The disease rapidly progressed and the child died despite chemotherapy and primary tumour surgical debulking. We molecularly classified the tumour as a group 3 MBL; in addition, we derived stem-like cells (SLC) from a metastatic lesion. Primary tumour, metastases and SLC were further analysed, particularly focusing on features linked to the cutaneous dissemination. Indeed, molecules involved in angiogenesis, cell invasion and epidermal growth factor signalling resulted highly expressed. The present report describes a very rare case of subcutaneous metastatic MBL. The tumour, metastases and SLC have been clinically, pathologically and molecularly characterized. Our case is an example of multidisciplinary approach aiming to characterize MBL aggressive behaviour

  17. Breast Implant Informed Consent Should Include the Risk of Anaplastic Large Cell Lymphoma.

    Science.gov (United States)

    Clemens, Mark W; Miranda, Roberto N; Butler, Charles E

    2016-04-01

    Breast implant-associated anaplastic large cell lymphoma (ALCL) is a rare T-cell lymphoma arising around breast implants. Public awareness has increased following a safety communication warning of the association of breast implant-associated ALCL by the U.S. Food and Drug Administration in 2011. Difficulty with determining an accurate assessment of risk, including diagnosis, or standardized treatment regimen has led surgeons to commonly omit preoperative discussion of this rare and frequently misunderstood cancer. Risk disclosure is a form of respect for patient autonomy, and informed consent has positive practical and moral consequences for the practice of plastic surgery. A model of breast implant-associated ALCL informed consent implementation and health care provider education are reviewed with 1-year process follow-up at a tertiary cancer center. Breast implant-associated ALCL should be included during preoperative counseling on the risks of breast implantation when obtaining informed consent. Pertinent aspects of decision-making include disease awareness, presenting symptoms, and resources for concerned patients. Education of health care professionals and provision of patient-focused materials ensures effectiveness of the informed consent process. PMID:27018666

  18. Galectin-1-mediated cell adhesion, invasion and cell death in human anaplastic large cell lymphoma: Regulatory roles of cell surface glycans

    OpenAIRE

    Suzuki, Osamu; Abe, Masafumi

    2014-01-01

    Galectin-1 is known to be one of the extracellular matrix proteins. To elucidate the biological roles of galectin-1 in cell adhesion and invasion of human anaplastic large cell lymphoma, we performed cell adhesion and invasion assays using the anaplastic large cell lymphoma cell line H-ALCL, which was previously established in our laboratory. From the cell surface lectin array, treatment with neuraminidase from Arthrobacter ureafaciens which cleaves all linkage types of cell surface sialic ac...

  19. {sup 18}F-FDG PET in Patients with Primary Systemic Anaplastic Large Cell Lymphoma: Differential Features According to Expression of Anaplastic Lymphoma Kinase

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    Lee, Dong Yun; Lee, Jong Jin; Park, Seol Hoon; Chae, Sunyoung; Kim, Shin; Yoon, Dok Hyun; Suh, Cheolwon; Huh, Jooryung; Ryu, Jinsook [Univ. of Ulsan College of Medicine, Seoul (Korea, Republic of)

    2013-12-15

    Primary systemic anaplastic large cell lymphoma (ALCL) is divided into two entities according to the expression of anaplastic lymphoma kinase (ALK). We investigated {sup 18}F-fluorodeoxyglucose positron emission tomography ({sup 18}F-FDG PET) findings in primary systemic ALCL according to ALK expression. Thirty-seven patients who had baseline PET before CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone)-based chemotherapy were enrolled. Among them, patients who underwent interim and/or post-therapy PET were further investigated for the treatment response and survival analysis. Baseline PET was analyzed visually and semi-quantitatively using peak SUV, and interim and post-therapy PETs were visually analyzed. All cases were {sup 18}F-FDG-avid on baseline PET. The peak SUV of ALK-positive ALCL (n =16, 18.7±10.5) was higher than that of ALK-negative ALCL (n =21, 10.0±4.9) (P =0.006). In ALK-negative ALCL, complete response (CR) rate in negative-interim PET was higher than positive-interim PET (100 % vs 37.5 %, P=0.02); however, there was no such difference in ALK-positive ALCL (100 % vs 75 %, P =0.19). The 3-year progression-free survival (PFS) was not significantly different between ALK-positive and ALK-negative ALCL (72.7 % vs 47.6 %, P =0.34). In ALK-negative ALCL, negative interim and post-therapy PET patients had better 3-year PFS than positive interim (83.3 % vs 25.0 %, P =0.06) and post-therapy PET patients (70.0%vs 20.0 %, P =0.04). In contrast, ALK-positive ALCL had no such differences between PFS and PET results. On baseline PET, all cases showed {sup 18}F-FDG avidity, and ALK expression was related to higher {sup 18}F-FDG uptake. ALK-positive patients tend to have better PFS than ALK-negative patients. Negative-interim PET was a good indicator of CR, and interim or post-therapy PET was helpful for predicting the prognosis only in the ALK-negative group.

  20. ALK-positive anaplastic large cell lymphoma with prominent bone involvement in a 13-year-old boy

    Directory of Open Access Journals (Sweden)

    Tian C

    2016-01-01

    Full Text Available Chen Tian, Yong Yu, Hongliang Yang, Lei Zhu, Yafei Wang, Yizhuo Zhang Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, People’s Republic of China Introduction: Anaplastic lymphoma kinase-positive (ALK+ anaplastic large cell lymphoma (ALCL is a type of non-Hodgkin lymphoma, which has strong expression of cluster of differentiation (CD-30 and ALK. ALCL sometimes can involve the bone marrow, and in advanced stages, it can produce destructive bone lesions. But ALK+ ALCL with prominent bone involvement is very rare, especially in children. Case report: A 13-year-old boy presented with waist pain and low-grade fever for 8 months. The biopsy of soft tissue lesions around the thoracic spine showed that these cells were positive for ALK-1, CD30, leukocyte common antigen, CD3, CD4, and CD8, as well as being negative for epithelial membrane antigen and pan-cytokeratin, which revealed ALCL. After six cycles of a regimen consisting of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone/methotrexate and cytarabine (hyper-CVAD/MA and autologous hematopoietic stem cell transplantation, he achieved complete remission (CR. Conclusion: It is generally believed that the regimen consisting of cyclophosphamide, hydroxydaunorubicin (doxorubicin, vincristine, and prednisolone (CHOP is also applicable to ALCL. Because of the tendency of rapid progression and the frequency of B symptoms, ALCL in children and young adults is treated with high-grade chemotherapy such as hyper-CVAD/MA. Keywords: anaplastic large cell lymphoma, anaplastic lymphoma kinase, bone involvement, hyper-CVAD/MA

  1. Prognostic significance and therapeutic potential of the activation of anaplastic lymphoma kinase/protein kinase B/mammalian target of rapamycin signaling pathway in anaplastic large cell lymphoma

    International Nuclear Information System (INIS)

    Activation of the protein kinase B/mammalian target of rapamycin (AKT/mTOR) pathway has been demonstrated to be involved in nucleophosmin-anaplastic lymphoma kinase (NPM-ALK)-mediated tumorigenesis in anaplastic large cell lymphoma (ALCL) and correlated with unfavorable outcome in certain types of other cancers. However, the prognostic value of AKT/mTOR activation in ALCL remains to be fully elucidated. In the present study, we aim to address this question from a clinical perspective by comparing the expressions of the AKT/mTOR signaling molecules in ALCL patients and exploring the therapeutic significance of targeting the AKT/mTOR pathway in ALCL. A cohort of 103 patients with ALCL was enrolled in the study. Expression of ALK fusion proteins and the AKT/mTOR signaling phosphoproteins was studied by immunohistochemical (IHC) staining. The pathogenic role of ALK fusion proteins and the therapeutic significance of targeting the ATK/mTOR signaling pathway were further investigated in vitro study with an ALK + ALCL cell line and the NPM-ALK transformed BaF3 cells. ALK expression was detected in 60% of ALCLs, of which 79% exhibited the presence of NPM-ALK, whereas the remaining 21% expressed variant-ALK fusions. Phosphorylation of AKT, mTOR, 4E-binding protein-1 (4E-BP1), and 70 kDa ribosomal protein S6 kinase polypeptide 1 (p70S6K1) was detected in 76%, 80%, 91%, and 93% of ALCL patients, respectively. Both phospho-AKT (p-AKT) and p-mTOR were correlated to ALK expression, and p-mTOR was closely correlated to p-AKT. Both p-4E-BP1 and p-p70S6K1 were correlated to p-mTOR, but were not correlated to the expression of ALK and p-AKT. Clinically, ALK + ALCL occurred more commonly in younger patients, and ALK + ALCL patients had a much better prognosis than ALK-ALCL cases. However, expression of p-AKT, p-mTOR, p-4E-BP1, or p-p70S6K1 did not have an impact on the clinical outcome. Overexpression of NPM-ALK in a nonmalignant murine pro-B lymphoid cell line, BaF3, induced the

  2. CD13-positive anaplastic large cell lymphoma of T-cell origin--a diagnostic and histogenetic problem.

    Science.gov (United States)

    Popnikolov, N K; Payne, D A; Hudnall, S D; Hawkins, H K; Kumar, M; Norris, B A; Elghetany, M T

    2000-12-01

    The expression of myelomonocytic-associated antigens in anaplastic large cell lymphomas (ALCLs), particularly those presenting in extranodal sites, can make their distinction from extramedullary myeloid cell tumors (EMCTs) or histiocytic tumors problematic. Yet, this distinction is clinically significant because of its therapeutic and prognostic implications. Herein, we describe a case of extranodal anaplastic lymphoma kinase-positive CD30-positive ALCL of T-cell origin in a 12-year-old boy, which was initially called an EMCT because of the expression of CD13 and HLA-DR detected by flow cytometry and the absence of other T-cell-related surface markers. However, the detection of cytoplasmic CD3 by flow cytometry prompted further studies. The tumor was composed of large cells with abundant slightly eosinophilic vacuolated cytoplasm and ovoid or reniform nuclei with a few small nucleoli. Using immunohistochemistry, the tumor was positive for CD45, CD30, CD45RO, and CD43 with a strong cytoplasmic and nuclear anaplastic lymphoma kinase stain. The tumor cells showed a T-cell clonal genotype. Electron microscopy revealed no ultrastructural features of myelomonocytic or histiocytic origin. The patient responded well to the chemotherapy and was in complete remission for 10 months at the time of submission of this manuscript. Review of the literature showed inconsistencies regarding the diagnosis, nomenclature, and, therefore, treatment and prognosis of these tumors. In addition, the CD13 expression in ALCL raises some histogenetic questions and may indicate origin from a pluripotent stem cell, misprogramming during malignant transformation, or a microenvironmental effect on lymphoid cell expression of surface antigens. Therefore, ALCL should be considered in the differential diagnosis of EMCTs or histiocytic tumors, particularly when surface marker lineage assignment is ambiguous. PMID:11100061

  3. Diffuse large B cell lymphoma of thyroid as a masquerader of anaplastic carcinoma of thyroid, diagnosed by FNA: a case report

    Directory of Open Access Journals (Sweden)

    Dehghani Mehdi

    2006-01-01

    Full Text Available Abstract Background Both thyroid lymphoma and anaplastic carcinoma of thyroid present with rapidly growing mass in eldery patients. Anaplastic carcinoma has high mortality rate and combination of surgery, radiation therapy and multidrug chemotherapy are the best chance for cure. Prognosis of thyroid lymphoma is excellent and chemotherapy for widespred lymphoms and radiotherapy with or without adjuvant chemotherapy for tumors localized to the gland, are the treatment of choice. Case report This article reports a 70 year old man presenting with diffuse neck swelling and hoarseness of few weeks duration. Fine needle aspiration was done and reported as anaplastic carcinoma of thyroid which thyroidectomy was planned. The slides were sent for second opinion. After review, with initial diagnosis of anaplastic carcinoma versus lymphoma, immunocytochemical study was performed. Smears were positive for B cell markers and negative for cytokeratin, so with the impression of diffuse large B cell lymphoma, the patient received two courses of chemotherapy by which the tumor disappeared during two weaks. Conclusion Despite previous reports, stating easy diagnosis of high-grade thyroid lymphoma on the grounds of cytomorphological features we like to emphasize, overlapping cytologic features of the curable high grade thyroid lymphoma form noncurable anaplastic thyroid carcinoma and usefulness of immunocytochemistry to differentiate these two disease.

  4. Locally advanced breast implant associated anaplastic large cell lymphoma: A case report of successful treatment with radiation and chemotherapy

    Directory of Open Access Journals (Sweden)

    Christopher Fleighton Estes

    2015-02-01

    Full Text Available The development of breast implant associated anaplastic large cell lymphoma (ALCL is a rare phenomenon. A typical presentation is an effusion associated with a breast implant. Less commonly, disease can become more advanced locoregionally or distantly. The optimal treatment schema is a topic of debate: localized ALCL can potentially be cured with implant removal alone, while other cases in the literature, including those that are more advanced, have been treated with varying combinations of surgery, chemotherapy, and external beam radiotherapy. This is a case report of breast implant ALCL with pathologically proven lymph node involvement, the fifth such patient reported. Our patient experienced a favorable outcome with radiation therapy and chemotherapy.

  5. A nanocomplex that is both tumor cell-selective and cancer gene-specific for anaplastic large cell lymphoma

    Directory of Open Access Journals (Sweden)

    Zu Youli

    2011-01-01

    Full Text Available Abstract Background Many in vitro studies have demonstrated that silencing of cancerous genes by siRNAs is a potential therapeutic approach for blocking tumor growth. However, siRNAs are not cell type-selective, cannot specifically target tumor cells, and therefore have limited in vivo application for siRNA-mediated gene therapy. Results In this study, we tested a functional RNA nanocomplex which exclusively targets and affects human anaplastic large cell lymphoma (ALCL by taking advantage of the abnormal expression of CD30, a unique surface biomarker, and the anaplastic lymphoma kinase (ALK gene in lymphoma cells. The nanocomplexes were formulated by incorporating both ALK siRNA and a RNA-based CD30 aptamer probe onto nano-sized polyethyleneimine-citrate carriers. To minimize potential cytotoxicity, the individual components of the nanocomplexes were used at sub-cytotoxic concentrations. Dynamic light scattering showed that formed nanocomplexes were ~140 nm in diameter and remained stable for more than 24 hours in culture medium. Cell binding assays revealed that CD30 aptamer probes selectively targeted nanocomplexes to ALCL cells, and confocal fluorescence microscopy confirmed intracellular delivery of the nanocomplex. Cell transfection analysis showed that nanocomplexes silenced genes in an ALCL cell type-selective fashion. Moreover, exposure of ALCL cells to nanocomplexes carrying both ALK siRNAs and CD30 RNA aptamers specifically silenced ALK gene expression, leading to growth arrest and apoptosis. Conclusions Taken together, our findings indicate that this functional RNA nanocomplex is both tumor cell type-selective and cancer gene-specific for ALCL cells.

  6. Biomarkers Provide Clues to Early Events in the Pathogenesis of Breast Implant-Associated Anaplastic Large Cell Lymphoma.

    Science.gov (United States)

    Kadin, Marshall E; Deva, Anand; Xu, Haiying; Morgan, John; Khare, Pranay; MacLeod, Roderick A F; Van Natta, Bruce W; Adams, William P; Brody, Garry S; Epstein, Alan L

    2016-07-01

    Almost 200 women worldwide have been diagnosed with breast implant-associated anaplastic large cell lymphoma (BIA-ALCL). The unique location and specific lymphoma type strongly suggest an etio-pathologic link between breast implants and BIA-ALCL. It is postulated that chronic inflammation via bacterial infection may be an etiological factor. BIA-ALCL resembles primary cutaneous ALCL (pcALCL) in morphology, activated T-cell phenotype, and indolent clinical course. Gene expression array analysis, flow cytometry, and immunohistochemistry were used to study pcALCL and BIA-ALCL cell lines. Clinical samples were also studied to characterize transcription factor and cytokine profiles of tumor cells and surrounding lymphocytes. BIA-ALCL and pcALCL were found to have common expression of transcription factors SOCS3, JunB, SATB1, and a cytokine profile suggestive of a Th1 phenotype. Similar patterns were observed in a CD30+ cutaneous lymphoproliferative disorder (LPD). The patterns of cytokine and transcription factor expression suggest that BIA-ALCL is likely to arise from chronic bacterial antigen stimulation of T-cells. Further analysis of cytokine and transcription factor profiles may allow early detection and treatment of BIA-ALCL leading to better prognosis and survival. LEVEL OF EVIDENCE 5: Risk. PMID:26979456

  7. Sialylation by β-galactoside α-2,6-sialyltransferase and N-glycans regulate cell adhesion and invasion in human anaplastic large cell lymphoma

    OpenAIRE

    Suzuki, Osamu; Abe, Masafumi; HASHIMOTO, YUKO

    2015-01-01

    The interaction between cell surface glycans and extracellular matrix (ECM) including galectins is known to be closely associated with tumor cell adhesion, invasion and metastasis. We analyzed the roles of cell surface sialylation or glycosylation in galectin or ECM-mediated cell adhesion and invasion of human malignant lymphoma cells. Neuraminidase from Arthrobacter ureafaciens (AU) treatment resulted in reduction of cell adhesion to galectin-8 in human anaplastic large cell lymphoma (H-ALCL...

  8. Locally Advanced Breast Implant-Associated Anaplastic Large-Cell Lymphoma: A Case Report of Successful Treatment with Radiation and Chemotherapy

    OpenAIRE

    Estes, Christopher F.; Zhang, Da; Reyes, Ruben; Korentager, Richard; McGinness, Marilee; Lominska, Christopher

    2015-01-01

    The development of breast implant-associated anaplastic large-cell lymphoma (ALCL) is a rare phenomenon. A typical presentation is an effusion associated with a breast implant. Less commonly, disease can be more advanced locoregionally or distantly. The optimal treatment schema is a topic of debate: localized ALCL can potentially be cured with implant removal alone, while other cases in the literature, including those that are more advanced, have been treated with varying combinations of surg...

  9. Anaplastic astrocytoma.

    Science.gov (United States)

    Grimm, Sean A; Chamberlain, Marc C

    2016-07-01

    Anaplastic astrocytoma (AA) is a diffusely infiltrating, malignant, astrocytic, primary brain tumor. AA is currently defined by histology although future classification schemes will include molecular alterations. AA can be separated into subgroups, which share similar molecular profiles, age at diagnosis and median survival, based on 1p/19q co-deletion status and IDH mutation status. AA with co-deletion of chromosomes 1p and 19q and IDH mutation have the best prognosis. AA with IDH mutation and no 1p/19q co-deletion have intermediate prognosis and AA with wild-type IDH have the worst prognosis and share many molecular alterations with glioblastoma. Treatment of noncodeleted AA based on preliminary results from the CATNON clinical trial consists of maximal safe resection followed by radiotherapy with post-radiotherapy temozolomide (TMZ) chemotherapy. The role of concurrent TMZ and whether IDH1 subgroups benefit from TMZ is currently being evaluated in the recently completed randomized, prospective Phase III clinical trial, CATNON. PMID:27230974

  10. Chemotherapy-resistant breast implant-associated anaplastic large cell lymphoma

    OpenAIRE

    Parthasarathy, Muralidharan; Orrell, Julian; Mortimer, Caroline; Ball, Liz

    2013-01-01

    A 43-year-old woman presented with a few weeks’ history of discomfort and swelling in her left breast. She had undergone bilateral breast augmentation 8 years previously. There were no risk factors for breast cancer. Clinical examination, mammography and breast ultrasound revealed a large left breast mass adjacent to the breast implant with enlarged axillary lymph nodes. Owing to diagnostic uncertainty, core biopsies were sent to a specialist unit which confirmed breast implant-associated ana...

  11. Extrinsic apoptotic pathways: A new potential "Target" for more sufficient therapy in a case of cutaneous anaplastic large CD30+ ALK-T--cell lymphoma

    Directory of Open Access Journals (Sweden)

    Georgi Tchernev

    2011-01-01

    Full Text Available The primary cutaneous T-cell lymphomas (CTCL represent a clonal T-lymphocyte proliferation infiltrating the skin. CD30+ T-cell lymphomas present clinically as nodules with a diameter between 1 and 15 cm, mostly in elderly patients. The role of the CD30 molecule in patients suffering from T-cell lymphomas is not completely clear yet. The signal transduction pathway which includes CD30 seems to play a key role in tumor progression. In certain forms of T-cellular lymphomas, the interaction between CD30/CD30-ligand is able to provoke apoptosis of the "tumor lymphocytes". The modern conceptions of the pathogenesis of T-cell lymphomas include disorders in the pathways involved in programmed cellular death and disregulation in the expression of certain of its regulatory molecules. We are presenting an unusual case of a female patient with a primary cutaneous form of CD30 + /ALK− anaplastic large T-cell lymphoma. Upon the introduction of systemic PUVA, (psoralen plus ultraviolet light radiation combined with beam therapy, a complete remission could be noticed. Eight months later, we observed a local recurrence, which was overcome by CHOP chemotherapy (Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin, Vincristin (Oncovin®, Predniso(lon. Six months later, new cutaneous lesions had been noticed again. A new therapeutic hope for the patients with anaplastic large CTCL is actually based on the influence of the activity of the different apoptotic pathways. Death ligands, including tumor necrosis factor (TNF-α, CD95L/FasL, and TRAIL, mediate also some important safeguard mechanisms against tumor growth in patients with CD30 + cutaneous anaplastic large T-cell lymphomas and critically contribute to lymphocyte homeostasis.

  12. Brentuximab vedotin in children and adolescents with Hodgkin’s lymphoma and anaplastic large cell lymphoma – literature review and own experience

    OpenAIRE

    N. V. Myakova; D. A. Evstratov; D. S. Abramov; D. M. Konovalov; A. V. Pshonkin; D. V. Litvinov

    2016-01-01

    Despite significant advances in the treatment of lymphomas in children remain a small proportion of patients with refractory or recurrent disease. An effective approach to the treatment of such patients – not only is the second line chemotherapy, but the use of the new targeted therapies. An example of this approach is the use of brentuximab vedotin (antibody-drug conjugate directed to the CD30) in relapsed Hodgkin’s lymphoma and anaplastic large cell lymphoma. Literature review and own exper...

  13. Aberrant expression and biological significance of Sox2, an embryonic stem cell transcriptional factor, in ALK-positive anaplastic large cell lymphoma

    International Nuclear Information System (INIS)

    Sox2 (sex-determining region Y-Box) is one of the master transcriptional factors that are important in maintaining the pluripotency of embryonic stem cells (ESCs). In line with this function, Sox2 expression is largely restricted to ESCs and somatic stem cells. We report that Sox2 is expressed in cell lines and tumor samples derived from ALK-positive anaplastic large cell lymphoma (ALK+ALCL), for which the normal cellular counterpart is believed to be mature T-cells. The expression of Sox2 in ALK+ALCL can be attributed to nucleophosmin-anaplastic lymphoma kinase (NPM-ALK), the oncogenic fusion protein carrying a central pathogenetic role in these tumors. By confocal microscopy, Sox2 protein was detectable in virtually all cells in ALK+ALCL cell lines. However, the transcriptional activity of Sox2, as assessed using a Sox2-responsive reporter construct, was detectable only in a small proportion of cells. Importantly, downregulation of Sox2 using short interfering RNA in isolated Sox2active cells, but not Sox2inactive cells, resulted in a significant decrease in cell growth, invasiveness and tumorigenicity. To conclude, ALK+ALCL represents the first example of a hematologic malignancy that aberrantly expresses Sox2, which represents a novel mechanism by which NPM-ALK mediates tumorigenesis. We also found that the transcriptional activity and oncogenic effects of Sox2 can be heterogeneous in cancer cells

  14. Locally advanced breast implant-associated anaplastic large-cell lymphoma: a case report of successful treatment with radiation and chemotherapy.

    Science.gov (United States)

    Estes, Christopher F; Zhang, Da; Reyes, Ruben; Korentager, Richard; McGinness, Marilee; Lominska, Christopher

    2015-01-01

    The development of breast implant-associated anaplastic large-cell lymphoma (ALCL) is a rare phenomenon. A typical presentation is an effusion associated with a breast implant. Less commonly, disease can be more advanced locoregionally or distantly. The optimal treatment schema is a topic of debate: localized ALCL can potentially be cured with implant removal alone, while other cases in the literature, including those that are more advanced, have been treated with varying combinations of surgery, chemotherapy, and external beam radiotherapy. This is a case report of breast implant ALCL with pathologically proven lymph node involvement, the fifth such patient reported. Our patient experienced a favorable outcome with radiation therapy and chemotherapy. PMID:25741471

  15. Diffuse large B cell lymphoma of thyroid as a masquerader of anaplastic carcinoma of thyroid, diagnosed by FNA: a case report

    OpenAIRE

    Dehghani Mehdi; Omidvari Shapour; Daneshbod Yahya; Daneshbod Khosrow; Negahban Shahrzad

    2006-01-01

    Abstract Background Both thyroid lymphoma and anaplastic carcinoma of thyroid present with rapidly growing mass in eldery patients. Anaplastic carcinoma has high mortality rate and combination of surgery, radiation therapy and multidrug chemotherapy are the best chance for cure. Prognosis of thyroid lymphoma is excellent and chemotherapy for widespred lymphoms and radiotherapy with or without adjuvant chemotherapy for tumors localized to the gland, are the treatment of choice. Case report Thi...

  16. Galectin-1-mediated cell adhesion, invasion and cell death in human anaplastic large cell lymphoma: regulatory roles of cell surface glycans.

    Science.gov (United States)

    Suzuki, Osamu; Abe, Masafumi

    2014-05-01

    Galectin-1 is known to be one of the extracellular matrix proteins. To elucidate the biological roles of galectin-1 in cell adhesion and invasion of human anaplastic large cell lymphoma, we performed cell adhesion and invasion assays using the anaplastic large cell lymphoma cell line H-ALCL, which was previously established in our laboratory. From the cell surface lectin array, treatment with neuraminidase from Arthrobacter ureafaciens which cleaves all linkage types of cell surface sialic acid enhanced Arachis hypogaea (PNA), Helix pomatia (HPA) and Phaseolus vulgaris-L (L-PHA) lectin binding reactivity to cell surface of lymphoma cells suggesting that neuraminidase removes cell surface sialic acid. In cell adhesion and invasion assays treatment with neuraminidase markedly enhanced cell adhesion to galectin-1 and decreased cell invasive capacity through galectin-1. α2,6-linked sialic acid may be involved in masking the effect of the interaction between galectin-1 and cell surface glycans. H-ALCL cells expressed the β-galactoside-α2,6-sialyltransferase ST6Gal1. On resialylation assay by recombinant ST6Gal1 with CMP-Neu5Ac, α2,6-resialylation of L-PHA reactive oligosaccharide by ST6Gal1 resulted in inhibition of H-ALCL cell adhesion to galectin-1 compared to the desialylated H-ALCL cells. On knockdown experiments, knockdown of ST6Gal1 dramatically enhanced cell adhesion to galectin-1. N-glycosylation inhibitor swainsonine treatment resulted in enhancement of cell adhesion to galectin-1. In glycomic analysis using the lectin blocking assay treatment with PNA, Artocarpus integrifolia (Jacalin), Glycine max (SBA), Helix pomatia (HPA), Vicia villosa (VVA), Ulex europaeus (UEA-1), Triticum vulgaris (WGA), Canavalia ensiformis (ConA), Phaseolus vulgaris-L (L-PHA), Phaseolus vulgaris-E4 (E-PHA), Datura stramonium (DSA) lectins resulted in modulation of lymphoma cell to galectin-1 suggesting that several types of glycans may regulate cell adhesion to galectin-1 by

  17. Case report: a unique pediatric case of a primary CD8 expressing ALK-1 positive anaplastic large cell lymphoma of skeletal muscle

    Directory of Open Access Journals (Sweden)

    Gaiser Timo

    2012-04-01

    Full Text Available Abstract Primary involvement of skeletal muscle is a very rare event in ALK-1 positive anaplastic large cell lymphoma (ALCL. We describe a case of a 10-year old boy presenting with a three week history of pain and a palpable firm swelling at the dorsal aspect of the left thigh. Histological examination of the lesion revealed a tumoral and diffuse polymorphic infiltration of the muscle by large lymphoid cells. Tumor cells displayed eccentric, lobulated "horse shoe" or "kidney-shape" nuclei. The cells showed immunohistochemical positivity for CD30, ALK-1, CD2, CD3, CD7, CD8, and Perforin. Fluorescence in situ hybridization analysis revealed a characteristic rearrangement of the ALK-1 gene in 2p23 leading to the diagnosis of ALK-1 positive ALCL. Chemotherapy according to the ALCL-99-NHL-BFM protocol was initiated and resulted in a complete remission after two cycles. This case illustrates the unusual presentation of a pediatric ALCL in soft tissue with a good response to chemotherapy.

  18. A 16-Gene Signature Distinguishes Anaplastic Astrocytoma from Glioblastoma

    OpenAIRE

    Soumya Alige Mahabala Rao; Sujaya Srinivasan; Irene Rosita Pia Patric; Alangar Sathyaranjandas Hegde; Bangalore Ashwathnarayanara Chandramouli; Arivazhagan Arimappamagan; Vani Santosh; Paturu Kondaiah; Manchanahalli R Sathyanarayana Rao; Kumaravel Somasundaram

    2014-01-01

    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 mo...

  19. Epigenetic Silencing of the Proapoptotic Gene BIM in Anaplastic Large Cell Lymphoma through an MeCP2/SIN3a Deacetylating Complex

    Directory of Open Access Journals (Sweden)

    Rocco Piazza

    2013-05-01

    Full Text Available BIM is a proapoptotic member of the Bcl-2 family. Here, we investigated the epigenetic status of the BIM locus in NPM/ALK+ anaplastic large cell lymphoma (ALCL cell lines and in lymph node biopsies from NPM/ALK+ ALCL patients. We show that BIM is epigenetically silenced in cell lines and lymph node specimens and that treatment with the deacetylase inhibitor trichostatin A restores the histone acetylation, strongly upregulates BIM expression, and induces cell death. BIM silencing occurs through recruitment of MeCP2 and the SIN3a/histone deacetylase 1/2 (HDAC1/2 corepressor complex. This event requires BIM CpG methylation/demethylation with 5-azacytidine that leads to detachment of the MeCP2 corepressor complex and reacetylation of the histone tails. Treatment with the ALK inhibitor PF2341066 or with an inducible shRNA targeting NPM/ALK does not restore BIM locus reacetylation; however, enforced expression of NPM/ALK in an NPM/ALK-negative cell line significantly increases the methylation at the BIM locus. This study demonstrates that BIM is epigenetically silenced in NPM/ALK-positive cells through recruitment of the SIN3a/HDAC1/2 corepressor complex and that NPM/ALK is dispensable to maintain BIM epigenetic silencing but is able to act as an inducer of BIM methylation.

  20. The dichloromethane extract of the ethnomedicinal plant Neurolaena lobata inhibits NPM/ALK expression which is causal for anaplastic large cell lymphomagenesis.

    Science.gov (United States)

    Unger, Christine; Popescu, Ruxandra; Giessrigl, Benedikt; Laimer, Daniela; Heider, Susanne; Seelinger, Mareike; Diaz, Rene; Wallnöfer, Bruno; Egger, Gerda; Hassler, Melanie; Knöfler, Martin; Saleh, Leila; Sahin, Emine; Grusch, Michael; Fritzer-Szekeres, Monika; Dolznig, Helmut; Frisch, Richard; Kenner, Lukas; Kopp, Brigitte; Krupitza, Georg

    2013-01-01

    The present study investigates extracts of Neuolaena lobata, an anti-protozoan ethnomedicinal plant of the Maya, regarding its anti-neoplastic properties. Firstly, extracts of increasing polarity were tested in HL-60 cells analyzing inhibition of cell proliferation and apoptosis induction. Secondly, the most active extract was further tested in anaplastic large cell lymphoma (ALCL) cell lines of human and mouse origin. The dichloromethane extract inhibited proliferation of HL-60, human and mouse ALCL cells with an IC50 of ~2.5, 3.7 and 2.4 µg/ml, respectively and arrested cells in the G2/M phase. The extract induced the checkpoint kinases Chk1 and Chk2 and perturbed the orchestrated expression of the Cdc25 family of cell cycle phosphatases which was paralleled by the activation of p53, p21 and downregulation of c-Myc. Importantly, the expression of NPM/ALK and its effector JunB were drastically decreased, which correlated with the activation of caspase 3. Subsequently also platelet derived growth factor receptor β was downregulated, which was recently shown to be transcriptionally controlled by JunB synergizing with ALK in ALCL development. We show that a traditional healing plant extract downregulates various oncogenes, induces tumor suppressors, inhibits cell proliferation and triggers apoptosis of malignant cells. The discovery of the 'Active Principle(s)' is warranted. PMID:23135783

  1. Lobatin B inhibits NPM/ALK and NF-κB attenuating anaplastic-large-cell-lymphomagenesis and lymphendothelial tumour intravasation.

    Science.gov (United States)

    Kiss, Izabella; Unger, Christine; Huu, Chi Nguyen; Atanasov, Atanas Georgiev; Kramer, Nina; Chatruphonprasert, Waranya; Brenner, Stefan; McKinnon, Ruxandra; Peschel, Andrea; Vasas, Andrea; Lajter, Ildiko; Kain, Renate; Saiko, Philipp; Szekeres, Thomas; Kenner, Lukas; Hassler, Melanie R; Diaz, Rene; Frisch, Richard; Dirsch, Verena M; Jäger, Walter; de Martin, Rainer; Bochkov, Valery N; Passreiter, Claus M; Peter-Vörösmarty, Barbara; Mader, Robert M; Grusch, Michael; Dolznig, Helmut; Kopp, Brigitte; Zupko, Istvan; Hohmann, Judit; Krupitza, Georg

    2015-01-28

    An apolar extract of the traditional medicinal plant Neurolaena lobata inhibited the expression of the NPM/ALK chimera, which is causal for the majority of anaplastic large cell lymphomas (ALCLs). Therefore, an active principle of the extract, the furanoheliangolide sesquiterpene lactone lobatin B, was isolated and tested regarding the inhibition of ALCL expansion and tumour cell intravasation through the lymphendothelium. ALCL cell lines, HL-60 cells and PBMCs were treated with plant compounds and the ALK inhibitor TAE-684 to measure mitochondrial activity, proliferation and cell cycle progression and to correlate the results with protein- and mRNA-expression of selected gene products. Several endpoints indicative for cell death were analysed after lobatin B treatment. Tumour cell intravasation through lymphendothelial monolayers was measured and potential causal mechanisms were investigated analysing NF-κB- and cytochrome P450 activity, and 12(S)-HETE production. Lobatin B inhibited the expression of NPM/ALK, JunB and PDGF-Rβ, and attenuated proliferation of ALCL cells by arresting them in late M phase. Mitochondrial activity remained largely unaffected upon lobatin B treatment. Nevertheless, caspase 3 became activated in ALCL cells. Also HL-60 cell proliferation was attenuated whereas PBMCs of healthy donors were not affected by lobatin B. Additionally, tumour cell intravasation, which partly depends on NF-κB, was significantly suppressed by lobatin B most likely due to its NF-κB-inhibitory property. Lobatin B, which was isolated from a plant used in ethnomedicine, targets malignant cells by at least two properties: I) inhibition of NPM/ALK, thereby providing high specificity in combating this most prevalent fusion protein occurring in ALCL; II) inhibition of NF-κB, thereby not affecting normal cells with low constitutive NF-κB activity. This property also inhibits tumour cell intravasation into the lymphatic system and may provide an option to manage this

  2. Primary anaplastic large cell lymphoma of the breast arising in reconstruction mammoplasty capsule of saline filled breast implant after radical mastectomy for breast cancer: an unusual case presentation

    Directory of Open Access Journals (Sweden)

    Sur Monalisa

    2009-04-01

    Full Text Available Abstract Background Primary non-Hodgkin lymphoma (NHL of the breast represents 0.04–0.5% of malignant lesions of the breast and accounts for 1.7–2.2% of extra-nodal NHL. Most primary cases are of B-cell phenotype and only rare cases are of T-cell phenotype. Anaplastic large cell lymphoma (ALCL is a rare T-cell lymphoma typically seen in children and young adults with the breast being one of the least common locations. There are a total of eleven cases of primary ALCL of the breast described in the literature. Eight of these cases occurred in proximity to breast implants, four in relation to silicone breast implant and three in relation to saline filled breast implant with three out of the eight implant related cases having previous history of breast cancer treated surgically. Adjuvant postoperative chemotherapy is given in only one case. Secondary hematological malignancies after breast cancer chemotherapy have been reported in literature. However in contrast to acute myeloid leukemia (AML, the association between lymphoma and administration of chemotherapy has never been clearly demonstrated. Case Presentation In this report we present a case of primary ALCL of the breast arising in reconstruction mamoplasty capsule of saline filled breast implant after radical mastectomy for infiltrating ductal carcinoma followed by postoperative chemotherapy twelve years ago. Conclusion Primary ALK negative ALCL arising at the site of saline filled breast implant is rare. It is still unclear whether chemotherapy and breast implantation increases risk of secondary hematological malignancies significantly. However, it is important to be aware of these complications and need for careful pathologic examination of tissue removed for implant related complications to make the correct diagnosis for further patient management and treatment. It is important to be aware of this entity at this site as it can be easily misdiagnosed on histologic grounds and to exclude

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

    Directory of Open Access Journals (Sweden)

    Soumya Alige Mahabala Rao

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

  4. Clinicopathologic Features of Gastrointestinal Tract Involvement of Anaplastic Large Cell Lymphoma%累及胃肠道的间变性大细胞淋巴瘤的临床病理学特点

    Institute of Scientific and Technical Information of China (English)

    孙健; 周皎琳; 陈杰; 卢朝辉

    2012-01-01

    Objective To investigate the clinicopathological characteristics of gastrointestinal tract involvement of anaplastic large cell lymphoma ( ALCL ). Methods The clinicopathological features of four patients with ALCL that involved gastrointestinal tract were retrospectively analyzed using immunohistochemical study, T-cell receptor gene rearrangement analysis, and evaluation for Epstein Barr virus infection status. Results Most tumor cells in all these four cases are large and highly pleomorphic, and all four cases were classified as the "common pattern" ALCL Tumor cells in all four tumors expressed CD30, and expressed at least one cytotoxic maker. Two patients were confirmed to be with anaplastic lymphoma kinase ( ALK) -positive ALCL, and four patients were negative during in situ hybridization for Epstein-Barr virus-encoded RNA but showed clonal T-cell receptor gene rearrangement. Conclusion Gastrointestinal tract involvement of ALCL has the unique clinicopathological features.%目的 总结累及胃肠道的间变性大细胞淋巴瘤(ALCL)的临床病理学特点.方法 收集整理4例累及胃肠道的ALCL病例标本,对其进行临床病理分析、免疫组织化学检测、EB病毒编码的RNA (EBER)原位杂交检测及T细胞受体(TCR)基因重排检测.结果 4例病例中,肿瘤细胞均以多形性大细胞为主,归为普通型ALCL;均表现为弥漫、较强地表达CD30,且至少表达1种细胞毒性抗原;2例为间变性淋巴瘤激酶(ALK)阳性ALCL;4例EBER原位杂交检测均为阴性且均存在TCR基因克隆性重排.结论 累及胃肠道的ALCL具有独特的临床病理特点.

  5. [Successful long-term control of recurrent primary central nervous system anaplastic large cell lymphoma after autologous hematopoietic stem cell transplantation with concurrent whole brain and spinal cord radiotherapy].

    Science.gov (United States)

    Hiroshima, Yuki; Kaiume, Hiroko; Kirihara, Takehiko; Takeda, Wataru; Kurihara, Taro; Sato, Keijiro; Shimizu, Ikuo; Ueki, Toshimitsu; Sumi, Masahiko; Ueno, Mayumi; Ichikawa, Naoaki; Asano, Naoko; Watanabe, Masahide; Kobayashi, Hikaru

    2015-12-01

    A 24-year-old woman was hospitalized with seizures in 2002. Magnetic resonance imaging demonstrated an intraspinal mass and inhomogeneous gadolinium enhancement along the cerebrospinal meninges. Cerebrospinal fluid (CSF) cytology showed large atypical cells expressing CD2, cytoplasmic CD3, CD7, CD13 and CD30. The patient was finally diagnosed with primary central nervous system anaplastic large cell lymphoma (ALCL). She completed 5 courses of methotrexate (MTX)/ procarbazine (PCZ)/ vincristine (VCR) (MPV) chemotherapy, followed by 2 courses of high dose cytarabine (AraC) and achieved a complete remission. In 2003, she suffered from headache. CSF analysis showed atypical lymphoid cells expressing CD 30. First CNS relapse was diagnosed. She then underwent autologous peripheral blood stem cell transplantation (auto-PBSCT) after administration of thiotepa, buslfan, and cyclophosphamide. However, second CNS relapse occurred in 2004. She received 5 courses of MPV chemotherapy followed by 36 Gy of craniospinal irradiation. Although there was no recurrence of the CNS disease, a third relapse was detected in the right breast in 2009. Pathological and immunohistochemistry analysis revealed ALK-1 positive ALCL. She was treated with 6 courses of cyclophosphamide/adriamycin/vincristine/predonine (CHOP) chemotherapy and 30.6 Gy of local radiation therapy. She has remained in remission for 6 years, to date, since the last therapy and has an excellent quality of life. PMID:26725359

  6. Anaplastic thyroid cancer, tumorigenesis and therapy.

    LENUS (Irish Health Repository)

    O'Neill, J P

    2010-03-01

    Anaplastic thyroid cancer (ATC) is a fatal endocrine malignancy. Current therapy fails to significantly improve survival. Recent insights into thyroid tumorigenesis, post-malignant dedifferentiation and mode of metastatic activity offer new therapeutic strategies.

  7. Anaplastic myeloma in systemic lupus erythematosus.

    Science.gov (United States)

    Butler, R C; Thomas, S M; Thompson, J M; Keat, A C

    1984-01-01

    We describe a patient with systemic lupus erythematosus who developed an unusual form of anaplastic myeloma. Possible relationships between the two disease, and the role played by immunosuppressive therapy, are discussed. Images PMID:6476924

  8. Leptomeningeal metastases from anaplastic thyroid carcinoma

    International Nuclear Information System (INIS)

    Anaplastic thyroid carcinoma is an extremely aggressive neoplasm that accounts for 1-3% of all thyroid cancers. ' Most patients have metastatic disease at presentation and die in a short period of time, often with uncontrolled local disease. We report a case of anaplastic thyroid cancer characterised by good response to initial treatment both locally and in distant metastases, and the subsequent development of refractory metastatic disease in an unusual site, the leptomeninges

  9. Pleomorphic xanthoastrocytoma with anaplastic features

    Directory of Open Access Journals (Sweden)

    Cheng ZHI

    2015-08-01

    Full Text Available Objective  To explore the clinical pathological characteristics, immunophenotyping, diagnosis and differential diagnosis and prognosis of pleomorphic xanthoastrocytoma (PXA with anaplastic features.  Methods  HE staining was used for histological observation. The expressions of glial fibrillary acidic protein (GFAP, vimentin (Vim, CD34, epithelial membrane antigen (EMA, progestrone receptor (PR, neurofilment protein (NF, neuronal nuclei (NeuN, synaptophysin (Syn, Nestin (Nes, S-100 protein (S-100, P53 and Ki-67 labeling index were detected by immunohistochemical method. BRAF mutation was detected by polymerase chain reaction (PCR amplification.  Results  A 43-year-old male patient presented with repeatedly paroxysmal tic of limbs and disturbance of consciousness. Cranial MRI revealed multiple abnormal signals in left temporo-occipito-parietal lobe and posterior horn of lateral ventricle, with unclear borderline and cystic degeneration. Surgical removal of the lesion was performed. Histologically, the tumor was biphasic. One part was composed of spindle cells arranged in fascicles or as running water, with weird multinuclear giant cells. Abundant vacuolated lipidized cytoplasm could be seen. Mitosis and "map"-like necrosis were noted. Another part revealed the tumor cells were consistent in size and uniform in distribution, with loose background tissue. Immunohistochemistry showed tumor cells were diffusely positive for GFAP, Vim, S-100, Nes, CD34 and P53, and negative for EMA, Syn, NeuN and NF. Ki-67 labeling index was about 15%. Reticular fiber staining showed abundant reticular fibers in the tumor tissue. BRAF mutation detected by PCR amplification was not found.  Conclusions  Classified as grade Ⅱ in the World Health Organization (WHO classification, the prognosis of PXA is good. A diagnosis of PXA with anaplastic features should be considered when the tumor demonstrates mitotic activity > 5/10 high power field (HPF and/or areas of

  10. TCF12 is mutated in anaplastic oligodendroglioma

    OpenAIRE

    Labreche, Karim; Simeonova, Iva; Kamoun, Aurélie; Gleize, Vincent; Chubb, Daniel; Letouzé, Eric; Riazalhosseini, Yasser; Dobbins, Sara E; Elarouci, Nabila; Ducray, Francois; De Reyniès, Aurélien; Zelenika, Diana; Wardell, Christopher P.; Frampton, Mathew; Saulnier, Olivier

    2015-01-01

    Anaplastic oligodendroglioma (AO) are rare primary brain tumours that are generally incurable, with heterogeneous prognosis and few treatment targets identified. Most oligodendrogliomas have chromosomes 1p/19q co-deletion and an IDH mutation. Here we analysed 51 AO by whole-exome sequencing, identifying previously reported frequent somatic mutations in CIC and FUBP1. We also identified recurrent mutations in TCF12 and in an additional series of 83 AO. Overall, 7.5% of AO are mutated for TCF12...

  11. Clinical analysis of primary anaplastic carcinoma of the small intestine

    Institute of Scientific and Technical Information of China (English)

    Tsutomu Namikawa; Kazuhiro Hanazaki

    2009-01-01

    Primary anaplastic carcinoma is a rare variant of small intestinal cancer. Most reports of primary anaplastic carcinoma of the small intestine are isolated case reports, therefore the clinicopathological features, therapeutic management, and surgical outcome of this tumor type remain unclear. This review analyzes the available clinical characteristics of primary anaplastic carcinoma of the small intestine and investigates key differences from differentiated adenocarcinoma of the small intestine. A Medline search was performed using the keywords 'small intestine' and 'anaplastic carcinoma' or 'undifferentiated carcinoma'. Additional articles were obtained from references with in the papers identified by the Medline search. The literature revealed a poor prognosis for patients who underwent surgical resection for anaplastic carcinoma of the small intestine, which gave a 3-year overall survival rate of 10.8% and a median survival time of 5.0 mo. The literature suggests that anaplastic carcinoma is markedly more aggressive than differentiated adenocarcinoma of the small intestine. Surgical resection with the aim of complete tumor removal provides the only beneficial therapeutic option for patients with anaplastic carcinoma of the small intestine, because chemotherapy and radiation therapy have no significant effect on the rate of survival. However, despite complete tumor resection, most patients with anaplastic carcinoma of the small intestine are at great risk of disease recurrence. Multicenter clinical trials are expected to provide additional therapeutic strategies and establish the efficacy of multimodality adjuvant therapy. This report also highlights the importance of a systematic diagnostic approach for anaplastic carcinoma of the small intestine.

  12. Genomic Landscape of poorly Differentiated and Anaplastic Thyroid Carcinoma.

    Science.gov (United States)

    Xu, Bin; Ghossein, Ronald

    2016-09-01

    Poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC) are aggressive thyroid tumors associated with a high mortality rate of 38-57 % and almost 100 % respectively. Several recent studies utilizing next generation sequencing techniques have shed lights on the molecular pathogenesis of these tumors, providing evidence to support a stepwise tumoral progression from well-differentiated to poorly differentiated, and finally to anaplastic thyroid carcinomas. While BRAF (V600E) and RAS mutations remain the main drivers in aggressive thyroid carcinoma, PDTC and ATC gains additional mutations, e.g., TERT promoter mutation, TP53 mutation, as well as frequent alterations in PIK3CA-PTEN-AKT-mTOR pathway, SWI-SNF complex, histomethyltransferases, and mismatch repair genes. RAS-mutated PDTCs are commonly associated with a histologic phenotype defined by Turin proposal, high frequency of distant metastasis, high thyroid differentiation score, and a RAS-like gene expression profile, whereas BRAF-mutated PDTCs are usually defined solely by the Memorial Sloan Kettering Cancer Center (MSKCC) criteria with a propensity for nodal metastasis and are less differentiated with a BRAF-like expression signature. Such demarcation is largely lost in ATC which is characterized by genomic complexity, heavy mutation burden, and profound undifferentiation. Additionally, several molecular events, e.g., EIF1AX mutation, mutation burden, and chromosome 1q gain in PDTCs, as well as EIF1AX mutation, chromosome 13q loss, and 20q gains in ATCs, may serve as adverse prognostic markers predicting poor clinical outcome. PMID:27372303

  13. h-prune affects anaplastic thyroid cancer invasion and metastasis.

    Science.gov (United States)

    Nambu, Junko; Kobayashi, Tsuyoshi; Hashimoto, Masakazu; Tashiro, Hirotaka; Sugino, Keizo; Shimamoto, Fumio; Kikuchi, Akira; Ohdan, Hideki

    2016-06-01

    Anaplastic thyroid cancer is one of the most aggressive human malignancies and is resistant to multimodal treatments. The expression of h-prune, the human homologue of Drosophila prune, has been reported to be correlated with progression and aggressiveness in various cancers including breast, colorectal and pancreatic cancers. We examined the role of h-prune in anaplastic thyroid cancer cell migration, invasion and metastasis. Immunohistochemical analysis of h-prune was performed with 15 surgically resected specimens of anaplastic thyroid cancers. To investigate cell motility, Boyden chamber, wound healing and matrigel invasion assays were performed using cells from anaplastic thyroid cancer cell lines. A murine orthotopic thyroid cancer model was used to investigate metastatic ability. In the immunohistochemical analysis, only weak focal or no staining of h-prune was observed in non-tumor tissue. In contrast, diffuse staining of h-prune was observed in anaplastic thyroid cancer and lymph node metastasis samples. Both inhibition of h-prune phosphodiesterase activity with dipyridamole and small interfering RNA for h-prune suppressed 8505C and KTC-3 cell motility. In addition, treatment with dipyridamole and decreased expression of h-prune suppressed tumor invasion and pulmonary metastasis in a NOD/Shi-scid, IL-2Rγnull (NOG) mouse orthotopic thyroid cancer model. In conclusion, h-prune is frequently expressed in anaplastic thyroid cancer cells and lymph nodes metastasis, and promotes migration and invasion of anaplastic thyroid cancer cells and metastasis in an anaplastic thyroid cancer model. Thus, h-prune shows promise as a targeting candidate against anaplastic thyroid cancer. PMID:27109060

  14. Anaplastic thyroid carcinoma: outcome and prognostic factors

    International Nuclear Information System (INIS)

    Purpose: Anaplastic carcinoma of the thyroid has been described as a rapidly progressive disease. We assessed the outcome and prognostic factors in patients with anaplastic thyroid carcinoma at our institution. Materials and Methods: Between 1975 and 1995, 37 patients were seen and treated at our institution with pathologically proven anaplastic carcinoma of the thyroid gland. Patients ranged in age from 49 to 97 years old (median 73 years) and females were represented in a 2:1 ratio. Many patients had history of prior benign thyroid disease (17) or low grade malignancy (6). Other medical illnesses were frequently present in these patients, including 5 with diabetes, 1 scleroderma, 1 sarcoidosis and 1 polycythemia vera. 12 patients had metastatic disease at presentation. 26 patients had locally advanced (T4) disease. The time from diagnosis to treatment was never longer than 1 month. Management was most often with biopsy only (22 patients) and local irradiation (34 patients, median dose 52.5 Gy). 15 patients had primary surgical resection, one of which had negative surgical margins. 11 patients received chemotherapy, 9 with Adriamycin-based regimens. Follow-up ranged from 4 months to 11 years, with a mean of 11 months. Results: 26 patients had a local response, either partial or complete, to their treatment regimen. However, systemic disease was an important cause of failure. 9 patients (24%) survived at least one year from diagnosis; 3 (8%) survived beyond two years. The development of metastases occurred quickly in originally localized disease, at a median of 2 months. Metastases occurred most commonly in the lung (11 of 14 cases), but also occured in brain (2), liver (1), bone (1) and pericardium (1). Performance status, sex, metastatic disease, hyperfractionation, treatment modalities, RT dose, age and response to treatment were assessed as prognostic factors for survival. On univariate analysis, age over 70 (p=.004) and failure to attain a complete response to

  15. Anaplastic Medullary Ependymoma Presenting as Subarachnoid Hemorrhage

    Directory of Open Access Journals (Sweden)

    Nicolas Nicastro

    2013-01-01

    Full Text Available A-41-year old man presented with violent thunderclap headache and a bilateral proprioceptive sensibility deficit of the upper limbs. Cerebral CT scan and MRI were negative. Lumbar puncture confirmed subarachnoid hemorrhage (SAH, but cerebral angiography was negative. Three months later, the patient presented with paraparesis, and a thorough work-up revealed a diffuse, anaplastic extramedullary C7-D10 ependymoma with meningeal carcinomatosis considered the source of hemorrhage. The patient went through a D5-D8 laminectomy, temozolomide chemotherapy, and radiotherapy. The situation remained stable for a few months. In this paper, we would like to emphasize that spinal masses should be considered in cases of SAH with negative diagnostic findings for aneurysms or arteriovenous malformation.

  16. Anaplastic lymphoma kinase status in rhabdomyosarcomas.

    Science.gov (United States)

    Yoshida, Akihiko; Shibata, Tatsuhiro; Wakai, Susumu; Ushiku, Tetsuo; Tsuta, Koji; Fukayama, Masashi; Makimoto, Atsushi; Furuta, Koh; Tsuda, Hitoshi

    2013-06-01

    Rhabdomyosarcoma is a rare soft tissue sarcoma that typically affects children, adolescents, and young adults. Despite treatment via a multidisciplinary approach, the prognosis of advance-stage rhabdomyosarcomas remains poor, and a new treatment strategy is needed. Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase that is a potential target for specific inhibitors. In this study, we investigated 116 rhabdomyosarcomas using a polymer-based ALK immunostaining method and correlated the results with clinicopathological parameters. In addition, we examined ALK status using dual-color fluorescence in situ hybridization, PCR, and sequencing. In immunohistochemical analysis, ALK was detected in 2 (6%) of 33 embryonal rhabdomyosarcomas, 42 (69%) of 61 alveolar rhabdomyosarcomas, and 0 (0%) of 22 other subtypes, including pleomorphic, adult-spindle-cell/sclerosing, and epithelioid variants. Compared with ALK-negative alveolar rhabdomyosarcomas, ALK-positive ones are presented with metastatic spread more frequently and showed a greater extent of myogenin reactivity. Overall survival was not associated with ALK expression. FOXO1 rearrangement was significantly associated with ALK immunoreactivity. The median ALK copy number was greater in ALK-positive tumors than in ALK-negative tumors. Most (93%) cases tested showed no selective increase in the ALK gene dosage. ALK selective amplification and low-level selective gain were noted in one and three cases, respectively. Further, a high-polysomy pattern (≥4 ALK copies in ≥40% of cells) was observed in seven cases. A significant increase in the ALK copy number was exclusive to the ALK-immunopositive cohort, but it was uncommon, accounting for only 30% of the 37 ALK-positive rhabdomyosarcomas. ALK gene rearrangement was not observed in either cohort, while an ALK somatic mutation (I1277T) was found in one ALK-negative embryonal case. Although it remains controversial whether ALK expression without gene rearrangement

  17. Anaplastic carcinoma following well-differentiated thyroid cancer: etiological considerations

    International Nuclear Information System (INIS)

    Most cases of anaplastic thyroid carcinoma can be pathologically and often historically associated with the presence of low-grade (differentiated) cancer in the thyroid. That radiation therapy to the differentiated tumor plays an etiologic role in the transformation of a differentiated to an undifferentiated tumor has been suggested. If such therapy can be implicated, is there a difference in risk between external radiotherapy or radioactive iodine. Review of the literature discloses that more anaplastic carcinoma of the thyroid develop in patients without a history of prior radiation than in individuals who have received radiation. We report our recent experience with two patients who demonstrated the sequence of well-differentiated followed by anaplastic thyroid cancer subsequent to radiation and review the question

  18. The emerging pathogenic and therapeutic importance of the anaplastic lymphoma kinase gene.

    LENUS (Irish Health Repository)

    Kelleher, Fergal C

    2012-02-01

    The anaplastic lymphoma kinase gene (ALK) is a gene on chromosome 2p23 that has expression restricted to the brain, testis and small intestine but is not expressed in normal lymphoid tissue. It has similarity to the insulin receptor subfamily of kinases and is emerging as having increased pathologic and potential therapeutic importance in malignant disease. This gene was originally established as being implicated in the pathogenesis of rare diseases including inflammatory myofibroblastic tumour (IMT) and ALK-positive anaplastic large cell lymphoma, which is a subtype of non-Hodgkin\\'s lymphoma. Recently the number of diseases in which ALK is implicated in their pathogenesis has increased. In 2007, an inversion of chromosome 2 involving ALK and a fusion partner gene in a subset of non-small cell lung cancer was discovered. In 2008, publications emerged implicating ALK in familial and sporadic cases of neuroblastoma, a childhood cancer of the sympatho-adrenal system. Chromosomal abnormalities involving ALK are translocations, amplifications or mutations. Chromosomal translocations are the longest recognised ALK genetic abnormality. When translocations occur a fusion gene is created between ALK and a gene partner. This has been described in ALK-positive anaplastic large cell lymphoma in which ALK is fused to NPM (nucleolar protein gene) and in non-small cell lung cancer where ALK is fused to EML4 (Echinoderm microtubule-associated protein 4). The most frequently described partner genes in inflammatory myofibroblastic tumour are tropomyosin 3\\/4 (TMP3\\/4), however in IMTs a diversity of ALK fusion partners have been found, with the ability to homodimerise a common characteristic. Point mutations and amplification of the ALK gene occur in the childhood cancer neuroblastoma. Therapeutic targeting of ALK fusion genes using tyrosine kinase inhibition, vaccination using an ALK specific antigen and treatment using viral vectors for RNAi are emerging potential therapeutic

  19. Successful radiopeptide targeting of metastatic anaplastic meningioma: Case report

    Directory of Open Access Journals (Sweden)

    Biersack Hans-Jürgen

    2011-08-01

    Full Text Available Abstract A patient with anaplastic meningioma and lung metastases resistant to conventional treatment underwent radiopeptide therapy with 177Lu- DOTA-octreotate in our institute. The treatment resulted in significant improvement in patient's quality of life and inhibition of tumor progression. This case may eventually help to establish the value of radiopeptide therapy in patients with this rare condition.

  20. Successful radiopeptide targeting of metastatic anaplastic meningioma: Case report

    International Nuclear Information System (INIS)

    A patient with anaplastic meningioma and lung metastases resistant to conventional treatment underwent radiopeptide therapy with 177Lu- DOTA-octreotate in our institute. The treatment resulted in significant improvement in patient's quality of life and inhibition of tumor progression. This case may eventually help to establish the value of radiopeptide therapy in patients with this rare condition

  1. A comparative evaluation of supervised and unsupervised representation learning approaches for anaplastic medulloblastoma differentiation

    Science.gov (United States)

    Cruz-Roa, Angel; Arevalo, John; Basavanhally, Ajay; Madabhushi, Anant; González, Fabio

    2015-01-01

    Learning data representations directly from the data itself is an approach that has shown great success in different pattern recognition problems, outperforming state-of-the-art feature extraction schemes for different tasks in computer vision, speech recognition and natural language processing. Representation learning applies unsupervised and supervised machine learning methods to large amounts of data to find building-blocks that better represent the information in it. Digitized histopathology images represents a very good testbed for representation learning since it involves large amounts of high complex, visual data. This paper presents a comparative evaluation of different supervised and unsupervised representation learning architectures to specifically address open questions on what type of learning architectures (deep or shallow), type of learning (unsupervised or supervised) is optimal. In this paper we limit ourselves to addressing these questions in the context of distinguishing between anaplastic and non-anaplastic medulloblastomas from routine haematoxylin and eosin stained images. The unsupervised approaches evaluated were sparse autoencoders and topographic reconstruct independent component analysis, and the supervised approach was convolutional neural networks. Experimental results show that shallow architectures with more neurons are better than deeper architectures without taking into account local space invariances and that topographic constraints provide useful invariant features in scale and rotations for efficient tumor differentiation.

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

    Science.gov (United States)

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

    2008-11-01

    A 2-year-old, female hedgehog presented with an 8-month history of progressive, ascending paresis/paralysis and was tentatively diagnosed with wobbly hedgehog syndrome. She died awaiting further diagnostic tests, and the owners consented to postmortem examination. Grossly, the bladder was large and flaccid and the cervical and lumbar spinal cord were regionally enlarged, light grey, and friable with multifocal hemorrhages. The thoracic spinal cord was grossly normal. Microscopically all regions of the spinal cord had similar changes, although the cervical and lumbar sections were most severely affected. These regions were completely effaced by a moderately cellular infiltration of highly pleomorphic polygonal to spindle shaped cells, mineralization, and necrosis, which were most consistent with anaplastic astrocytoma. The thoracic spinal cord white matter was similarly infiltrated by the neoplastic cells, with perivascular extension into the otherwise normal grey matter. A diagnosis of anaplastic astrocytoma was confirmed using immunohistochemical stains that were positive for glial fibrillary acidic protein and S100. PMID:18984799

  3. Anaplastic cerebral hemangiopericytoma: Rare variant of a rare disease

    Directory of Open Access Journals (Sweden)

    Purnima Thakur

    2015-01-01

    Full Text Available Intracranial hemangiopericytoma (HPC is a rare tumor of central nervous system, anaplastic type (grade 3 being the rarest. HPC closely mimics meningiomas in clinical and radiological features, thus, its diagnosis and treatment is a challenge. We report a rare case of histopathologically diagnosed anaplastic HPC of frontal lobe of the brain. A lady in her 60′s presented with neurological signs of impaired memory, headache, decreased vision and slurring of speech that gradually progressed to aphasia over a period of 2 months. A space occupying lesion was identified on magnetic resonance imaging in the left frontal region. Left frontal craniotomy and Simpson grade 1 excision of the tumor was done. Postoperative radiotherapy was administered in view of positive margins on histopathological specimen. We describe the clinical, radiological, and histological features of this tumor, its outcome on completion of treatment and on subsequent follow-up along with a review of the literature.

  4. Anaplastic carcinoma following well-differentiated thyroid cancer: etiological considerations.

    OpenAIRE

    Kapp, D S; LiVolsi, V. A.; Sanders, M M

    1982-01-01

    Most cases of anaplastic thyroid carcinoma can be pathologically and often historically associated with the presence of low-grade (differentiated) cancer in the thyroid. That radiation therapy to the differentiated tumor plays an etiologic role in the transformation of a differentiated to an undifferentiated tumor has been suggested. If such therapy can be implicated, is there a difference in risk between external radiotherapy or radioactive iodine? Review of the literature discloses that mor...

  5. Anaplastic Thyroid Carcinoma Following Radioactive Iodine Therapy for Graves' Disease

    OpenAIRE

    Kim, Sun Hwa; Kim, Hee Young; Jung, Kwang Yoon; Choi, Dong Seop; Kim, Sin Gon

    2013-01-01

    Radioactive iodine (RAI) therapy has been used as a treatment option for Graves' disease, and it has been widely accepted to be safe. On the other hand, some evidence suggests that RAI therapy is possibly associated with a small increased risk of thyroid cancer. Herein, we report a rare case of anaplastic thyroid carcinoma (ATC) associated with Graves' disease, following RAI treatment. A 42-year-old woman had been diagnosed with Graves' disease and although she was treated with an antithyroid...

  6. Anaplastic thyroid cancer: molecular pathogenesis and emerging therapies

    OpenAIRE

    Smallridge, Robert C.; Marlow, Laura A.; Copland, John A.

    2008-01-01

    Anaplastic thyroid cancer (ATC) is a rare malignancy. While external beam radiation therapy has improved locoregional control, the median survival of ∼ 4 months has not changed in more than half a century due to uncontrolled systemic metastases. The objective of this study was to review the literature in order to identify potential new strategies for treating this highly lethal cancer. PubMed searches were the principal source of articles reviewed. The molecular pathogenesis of ATC includes m...

  7. Anaplastic thyroid cancer Irish epidemiology and novel chemotherapeutic strategies

    OpenAIRE

    O'Neill, James Paul

    2009-01-01

    This body of work was conducted over a four year period. Within this timeframe we have conducted a National Epidemiology project, established a National Head and Neck Cancer database and completed Oncology laboratory investigations. Anaplastic thyroid cancer (ATC) is the most aggressive endocrine disease in nature. Within the thyroid gland a heterogeneous group of neoplasms may develop. These can range from well differentiated tumours with an excellent prognosis, to ATC tumours which prese...

  8. Ovarian mucinous cystadenoma with mural nodule of anaplastic carcinoma.

    OpenAIRE

    Hong, S. R.; Chun, Y. K.; Kim, Y. J.; Lim, K. T.; Kim, H S

    1998-01-01

    The occurrence of malignant mural nodule in benign cystic common epithelial tumor of the ovary have been reported in only three cases; the case one was mucinous cystadenoma with a mural nodule of fibrosarcoma and the others were of carcinomas. Our case was another rare case of ovarian mucinous cystadenoma with mural nodule of anaplastic carcinoma in a 42-year-old woman. The cystadenoma had an unilocular cystic cavity and a mural nodule with thick multinodular solid wall. The internal cystic w...

  9. Presence of anaplastic lymphoma kinase in inflammatory breast cancer

    OpenAIRE

    Robertson, Fredika M; Petricoin III, Emanuel F.; van Laere, Steven J; Bertucci, Francois; Chu, Khoi; Fernandez, Sandra V.; Mu, Zhaomei; Alpaugh, Katherine; Pei, Jianming; Circo, Rita; Wulfkuhle, Julia; Ye, Zaiming; Boley, Kimberly M; Liu, Hui; Moraes, Ricardo

    2013-01-01

    Although Inflammatory Breast Cancer (IBC) is recognized as the most metastatic variant of locally advanced breast cancer, the molecular basis for the distinct clinical presentation and accelerated program of metastasis of IBC is unknown. Reverse phase protein arrays revealed activation of the receptor tyrosine kinase, anaplastic lymphoma kinase (ALK) and biochemically-linked downstream signaling molecules including JAK1/STAT3, AKT, mTor, PDK1, and AMPKβ in pre-clinical models of IBC. To evalu...

  10. DNA methylation alterations in grade II- and anaplastic pleomorphic xanthoastrocytoma

    International Nuclear Information System (INIS)

    Pleomorphic xanthoastrocytoma (PXA) is a rare WHO grade II tumor accounting for less than 1% of all astrocytomas. Malignant transformation into PXA with anaplastic features, is unusual and correlates with poorer outcome of the patients. Using a DNA methylation custom array, we have quantified the DNA methylation level on the promoter sequence of 807 cancer-related genes of WHO grade II (n = 11) and III PXA (n = 2) and compared to normal brain tissue (n = 10) and glioblastoma (n = 87) samples. DNA methylation levels were further confirmed on independent samples by pyrosequencing of the promoter sequences. Increasing DNA promoter hypermethylation events were observed in anaplastic PXA as compared with grade II samples. We further validated differential hypermethylation of CD81, HCK, HOXA5, ASCL2 and TES on anaplastic PXA and grade II tumors. Moreover, these epigenetic alterations overlap those described in glioblastoma patients, suggesting common mechanisms of tumorigenesis. Even taking into consideration the small size of our patient populations, our data strongly suggest that epigenome-wide profiling of PXA is a valuable tool to identify methylated genes, which may play a role in the malignant progression of PXA. These methylation alterations may provide useful biomarkers for decision-making in those patients with low-grade PXA displaying a high risk of malignant transformation

  11. Metronomic chemotherapy in anaplastic thyroid carcinoma: A potentially feasible alternative to therapeutic nihilism

    Directory of Open Access Journals (Sweden)

    Swaroop Revannasiddaiah

    2015-01-01

    Full Text Available Anaplastic thyroid carcinoma (ATC is one of the most aggressive malignancies and prognostic outlook remains very dismal. Treatment most often is palliative in intent attempting to relieve the patients from local compressive symptoms in the neck. Radical surgery, radiotherapy (RT, and chemotherapy have not been tested in large prospective trials, and current evidence from retrospective series and small trials indicate only marginal survival benefits. Given the poor prognostic and therapeutic outlook, patients must be encouraged to be actively involved in the decision making process. We report the case of an elderly patient who had no response to palliative RT, and was treated with oral metronomic chemotherapy. The response to oral metronomic chemotherapy was dramatic, and the patient has enjoyed complete freedom from symptoms as well as radiologically exhibits a complete regression. Thus, we document the first ever use of a simple, cost-effective, and convenient oral metronomic chemotherapeutic regimen delivering a remarkable response in an elderly patient with ATC.

  12. Metronomic chemotherapy in anaplastic thyroid carcinoma: a potentially feasible alternative to therapeutic nihilism.

    Science.gov (United States)

    Revannasiddaiah, Swaroop; Madabhavi, Irappa; Bodh, Anita; Thakur, Priyanka; Sharma, Mukesh

    2015-01-01

    Anaplastic thyroid carcinoma (ATC) is one of the most aggressive malignancies and prognostic outlook remains very dismal. Treatment most often is palliative in intent attempting to relieve the patients from local compressive symptoms in the neck. Radical surgery, radiotherapy (RT), and chemotherapy have not been tested in large prospective trials, and current evidence from retrospective series and small trials indicate only marginal survival benefits. Given the poor prognostic and therapeutic outlook, patients must be encouraged to be actively involved in the decision making process. We report the case of an elderly patient who had no response to palliative RT, and was treated with oral metronomic chemotherapy. The response to oral metronomic chemotherapy was dramatic, and the patient has enjoyed complete freedom from symptoms as well as radiologically exhibits a complete regression. Thus, we document the first ever use of a simple, cost-effective, and convenient oral metronomic chemotherapeutic regimen delivering a remarkable response in an elderly patient with ATC. PMID:26009682

  13. The effect of low level laser on anaplastic thyroid cancer

    Science.gov (United States)

    Rhee, Yun-Hee; Moon, Jeon-Hwan; Ahn, Jin-Chul; Chung, Phil-Sang

    2015-02-01

    Low-level laser therapy (LLLT) is a non-thermal phototherapy used in several medical applications, including wound healing, reduction of pain and amelioration of oral mucositis. Nevertheless, the effects of LLLT upon cancer or dysplastic cells have been so far poorly studied. Here we report that the effects of laser irradiation on anaplastic thyroid cancer cells leads to hyperplasia. 650nm of laser diode was performed with a different time interval (0, 15, 30, 60J/cm2 , 25mW) on anaplastic thyroid cancer cell line FRO in vivo. FRO was orthotopically injected into the thyroid gland of nude mice and the irradiation was performed with the same method described previously. After irradiation, the xenograft evaluation was followed for one month. The thyroid tissues from sacrificed mice were undergone to H&E staining and immunohistochemical staining with HIF-1α, Akt, TGF-β1. We found the aggressive proliferation of FRO on thyroid gland with dose dependent. In case of 60 J/ cm2 of energy density, the necrotic bodies were found in a center of the thyroid. The phosphorylation of HIF-1α and Akt was detected in the thyroid gland, which explained the survival signaling of anaplastic cancer cell was turned on the thyroid gland. Furthermore, TGF-β1 expression was decreased after irradiation. In this study, we demonstrated that insufficient energy density irradiation occurred the decreasing of TGF-β1 which corresponding to the phosphorylation of Akt/ HIF-1α. This aggressive proliferation resulted to the hypoxic condition of tissue for angiogenesis. We suggest that LLLT may influence to cancer aggressiveness associated with a decrease in TGF-β1 and increase in Akt/HIF-1α.

  14. Cortical Anaplastic Ependymoma with Significant Desmoplasia: A Case Report and Literature Review

    Science.gov (United States)

    Elsharkawy, Alaa Eldin; Abuamona, Raid; Bergmann, Markus; Salem, Shadi; Gafumbegete, Evariste; Röttger, Ernst

    2013-01-01

    Ectopic brain anaplastic ependymomas with no connection to the ventricles are rare. We present a rare case of a 25-year-old male who presented with generalized convulsions. Computed tomography (CT), Magnetic Resonance Imaging (MRI), and magnetic resonance spectroscopy (MRS) showed characters of an intra- and extra-axial lesion. Intraoperatively, the lesion was a cortical solid mass that had no connections to the dura or to the ventricle. The histological diagnosis showed an anaplastic ependymoma with WHO grade III with distinctive desmoplasia. A literature review of ectopic anaplastic ependymomas regarding their clinical presentations, management, and prognostic factors was performed. There is a need to establish a clinically based histopathological grading system for anaplastic ependymomas. Ectopic anaplastic ependymomas should be included in the preoperative differential diagnosis. PMID:24455359

  15. Cortical Anaplastic Ependymoma with Significant Desmoplasia: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Alaa Eldin Elsharkawy

    2013-01-01

    Full Text Available Ectopic brain anaplastic ependymomas with no connection to the ventricles are rare. We present a rare case of a 25-year-old male who presented with generalized convulsions. Computed tomography (CT, Magnetic Resonance Imaging (MRI, and magnetic resonance spectroscopy (MRS showed characters of an intra- and extra-axial lesion. Intraoperatively, the lesion was a cortical solid mass that had no connections to the dura or to the ventricle. The histological diagnosis showed an anaplastic ependymoma with WHO grade III with distinctive desmoplasia. A literature review of ectopic anaplastic ependymomas regarding their clinical presentations, management, and prognostic factors was performed. There is a need to establish a clinically based histopathological grading system for anaplastic ependymomas. Ectopic anaplastic ependymomas should be included in the preoperative differential diagnosis.

  16. Combination chemotherapy (COMP protocol) and radiotherapy of anaplastic supratentorial gliomas

    International Nuclear Information System (INIS)

    Postoperative survival time and recurrence-free intervals in 116 consecutive patients with supratentorial grade III and IV gliomas (glioblastomas, gliosarcomas, anaplastic astrocytomas, and ependymomas) were compared in unselected groups receiving different forms of treatment. Postoperative high-voltage radiotherapy (31 patients, dosage 4,000-6,000 rads) and combined chemotherapy consisting of CCNU, vincristine, amethopterine, and procarbazine in 15-day circles (COMP protocol) (12 patients) showed the same median survival time of 10.6 months and comparable recurrence-free intervals of 6.8 and 7.0 months, respectively. These results were significantly different from a control group (39 patients) receiving best postoperative supportive (conventional) care (median survival 5.4 months, free interval 3.7 months). Combination of postoperative radiotherapy with simultaneous polychemotherapy (COMP protocol), evaluated in 18 patients, did not significantly change the recurrence-free interval (median 7.0 months), but increased the median survival time to 12.9 months, which was significantly superior to the two other treatment groups. The toxic side effects of COMP therapy were moderate and essentially haematological. In general, simultaneous radiation and chemical treatment was well tolerated after major tumour resection. These preliminary results of postoperative combination of radiation and polychemotherapy for anaplastic supratentorial gliomas appear encouraging, but further trials for optimization of combined therapeutic strategies are warranted. (author)

  17. Temozolomide Treatment for Pediatric Refractory Anaplastic Ependymoma with Low MGMT Protein Expression.

    Science.gov (United States)

    Komori, Kazutoshi; Yanagisawa, Ryu; Miyairi, Yosuke; Sakashita, Kazuo; Shiohara, Masaaki; Fujihara, Ikuko; Morita, Daisuke; Nakamura, Tomohiko; Ogiso, Yoshifumi; Sano, Kenji; Shirahata, Mitsuaki; Fukuoka, Kohei; Ichimura, Koichi; Shigeta, Hiroaki

    2016-01-01

    The benefit of postoperative chemotherapy for anaplastic ependymoma remains unknown. We report two pediatric patients with refractory anaplastic ependymoma treated with temozolomide (TMZ). We did not detect O(6) -methylguanine-DNA methyltransferase (MGMT) promoter methylation in tumor samples; however, MGMT protein expression was low. With TMZ treatment, one patient had a 7-month complete remission; the other, stable disease for 15 months. Three other patients did not respond to TMZ; two had high and one low MGMT expression, and two showed no MGMT promoter methylation. These findings suggest that TMZ may be effective for pediatric refractory anaplastic ependymoma with low MGMT protein expression. PMID:26305586

  18. Concomitant occurrence of EGFR (epidermal growth factor receptor) and KRAS (V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) mutations in an ALK (anaplastic lymphoma kinase)-positive lung adenocarcinoma patient with acquired resistance to crizotinib

    DEFF Research Database (Denmark)

    Rossing, Henrik H; Grauslund, Morten; Urbanska, Edyta M;

    2013-01-01

    events behind crizotinib-resistance currently remain largely uncharacterized. Thus, we report on an anaplastic lymphoma kinase-positive non-small cell lung carcinoma patient with concomitant occurrence of epidermal growth factor receptor and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog mutations...

  19. Anaplastic thyroid carcinoma: 91 patients treated by surgery and radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Junor, E.J.; Paul, J.; Reed, N.S. (Beatson Oncology Centre, Glasgow (United Kingdom))

    1992-04-01

    Ninety-one patients with histologically proven anaplastic carcinoma of the thyroid were referred to the Beatson Oncology Centre between 1961 and 1986. The female:male ratio was 2.4:1 and the median age at presentation was 70 (range 38-92) years. All patients had a thyroid mass at presentation and the most common symptoms were dyspnoea, dyspnagia and dysphonia. Five patients had a total thyroidectomy and 28 partial thyroidectomy. Ninety five per cent of patients received external beam radiotherapy. Results show dyspnoea to be the only symptom strongly influencing survival. Total or partial thyroidectomy is associated with increased survival. This association is most marked for patients presenting without dyspnoea. Eighty per cent of patients responded to radiotherapy. (Author).

  20. Anaplastic thyroid carcinoma: 91 patients treated by surgery and radiotherapy

    International Nuclear Information System (INIS)

    Ninety-one patients with histologically proven anaplastic carcinoma of the thyroid were referred to the Beatson Oncology Centre between 1961 and 1986. The female:male ratio was 2.4:1 and the median age at presentation was 70 (range 38-92) years. All patients had a thyroid mass at presentation and the most common symptoms were dyspnoea, dyspnagia and dysphonia. Five patients had a total thyroidectomy and 28 partial thyroidectomy. Ninety five per cent of patients received external beam radiotherapy. Results show dyspnoea to be the only symptom strongly influencing survival. Total or partial thyroidectomy is associated with increased survival. This association is most marked for patients presenting without dyspnoea. Eighty per cent of patients responded to radiotherapy. (Author)

  1. Anaplastic thyroid carcinoma: 91 patients treated by surgery and radiotherapy.

    Science.gov (United States)

    Junor, E J; Paul, J; Reed, N S

    1992-04-01

    Ninety-one patients with histologically proven anaplastic carcinoma of the thyroid were referred to the Beatson Oncology Centre between 1961 and 1986. The female:male ratio was 2.4:1 and the median age at presentation was 70 (range 38-92) years. All patients had a thyroid mass at presentation and the most common symptoms were dyspnoea, dysphagia and dysphonia. Five patients had a total thyroidectomy and 28 partial thyroidectomy. Ninety five per cent of patients received external beam radiotherapy. Results show dyspnoea to be the only symptom strongly influencing survival. Total or partial thyroidectomy is associated with increased survival. This association is most marked for patients presenting without dyspnoea. Eighty per cent of patients responded to radiotherapy. PMID:1582515

  2. Long-term control of disseminated pleomorphic xanthoastrocytoma with anaplastic features by means of stereotactic irradiation

    OpenAIRE

    Koga, Tomoyuki; Morita, Akio; Maruyama, Keisuke; Tanaka, Minoru; Ino, Yasushi; Shibahara, Junji; Louis, David N.; Reifenberger, Guido; Itami, Jun; Hara, Ryusuke; SAITO, Nobuhito; Todo, Tomoki

    2009-01-01

    Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytic neoplasm of the brain. Some PXAs are accompanied by anaplastic features and are difficult to manage because of frequent recurrences that lead to early death. No previous reports have demonstrated consistent efficacy of adjuvant radiotherapy or chemotherapy for this disease. We report a case of PXA with anaplastic features treated with stereotactic irradiation (STI) that resulted in long-term control of repeatedly recurring nodules throu...

  3. Cortical Anaplastic Ependymoma with Significant Desmoplasia: A Case Report and Literature Review

    OpenAIRE

    Alaa Eldin Elsharkawy; Raid Abuamona; Markus Bergmann; Shadi Salem; Evariste Gafumbegete; Ernst Röttger

    2013-01-01

    Ectopic brain anaplastic ependymomas with no connection to the ventricles are rare. We present a rare case of a 25-year-old male who presented with generalized convulsions. Computed tomography (CT), Magnetic Resonance Imaging (MRI), and magnetic resonance spectroscopy (MRS) showed characters of an intra- and extra-axial lesion. Intraoperatively, the lesion was a cortical solid mass that had no connections to the dura or to the ventricle. The histological diagnosis showed an anaplastic ependym...

  4. Focused Ultrasound Surgery for the Treatment of Recurrent Anaplastic Astrocytoma: A Preliminary Report

    Science.gov (United States)

    Park, Jung-Wuk; Jung, Shin; Jung, Tae-Young; Lee, Min-Cheol

    2006-05-01

    Anaplastic glioma is a highly aggressive tumor in the central nervous system. The conventional treatment for patients with anaplstic glioma consists of the combination of surgery, chemotherapy and radiotherapy. However, the effect of the currently available therapies is limited, and the prognosis is very poor in these patients. The purpose of this abstract is to introduce our preliminary experience of using focused ultrasound surgery (FUS) for the treatment of patients with recurrent anaplastic astrocytoma.

  5. Carfilzomib potentiates CUDC-101-induced apoptosis in anaplastic thyroid cancer

    Science.gov (United States)

    Zhang, Lisa; Boufraqech, Myriem; Lake, Ross; Kebebew, Electron

    2016-01-01

    Anaplastic thyroid cancer (ATC) is one of the most aggressive human malignancies, with no effective treatment currently available. Previously, we identified agents active against ATC cells, both in vitro and in vivo, using quantitative high-throughput screening of 3282 clinically approved drugs and small molecules. Here, we report that combining two of these active agents, carfilzomib, a second-generation proteasome inhibitor, and CUDC-101, a histone deacetylase and multi-kinase inhibitor, results in increased, synergistic activity in ATC cells. The combination of carfilzomib and CUDC-101 synergistically inhibited cellular proliferation and caused cell death in multiple ATC cell lines harboring various driver mutations observed in human ATC tumors. This increased anti-ATC effect was associated with a synergistically enhanced G2/M cell cycle arrest and increased caspase 3/7 activity induced by the drug combination. Mechanistically, treatment with carfilzomib and CUDC-101 increased p21 expression and poly (ADP-ribose) polymerase protein cleavage. Our results suggest that combining carfilzomib and CUDC-101 would offer an effective therapeutic strategy to treat ATC. PMID:26934320

  6. Anaplastic Lymphoma Kinase Rearrangement in Digestive Tract Cancer: Implication for Targeted Therapy in Chinese Population.

    Directory of Open Access Journals (Sweden)

    Jianming Ying

    Full Text Available Anaplastic lymphoma kinase (ALK rearrangements define a subgroup of lung cancer which is eligible to targeted kinase inhibition. The aim of this study is to observe the incidence rate of ALK fusion in a large cohort of Chinese digestive tract cancer patients.Tissue microarray (TMA was constructed from 808 digestive tract cancer cases, including 169 esophageal squamous cell carcinoma, 182 gastric cancer and 457 colorectal cancer (CRC cases. We tested all cases for ALK expression via a fully automated immunohistochemistry (IHC assay. The IHC-positive cases were subjected to fluorescence in situ hybridization (FISH, real-time polymerase chain reaction (qRT-PCR, target gene enrichment and sequencing for confirmation of ALK gene rearrangement and discovery of novel fusion partner.Among the tested cases, 2 (0.44% CRC cases showed positive both by IHC and FISH. By qRT-PCR, EML4-ALK fusion was found in one IHC-positive CRC case. In another IHC-positive CRC case, target gene enrichment and sequencing revealed ALK was fused to a novel partner, spectrin beta non-erythrocytic 1 (SPTBN1. One gastric cancer case showed partially positive IHC result, but no fusion was found by FISH and gene sequencing.The incidence rate of ALK gene fusion in Chinese CRC patients was 0.44%,but not detectable in gastric and esophageal cancers. The novel SPTBN1 -ALK fusion, together with other ALK fusion genes, may become a potential target for anti-ALK therapy.

  7. Increased p53 immunopositivity in anaplastic medulloblastoma and supratentorial PNET is not caused by JC virus

    International Nuclear Information System (INIS)

    p53 mutations are relatively uncommon in medulloblastoma, but abnormalities in this cell cycle pathway have been associated with anaplasia and worse clinical outcomes. We correlated p53 protein expression with pathological subtype and clinical outcome in 75 embryonal brain tumors. The presence of JC virus, which results in p53 protein accumulation, was also examined. p53 protein levels were evaluated semi-quantitatively in 64 medulloblastomas, 3 atypical teratoid rhabdoid tumors (ATRT), and 8 supratentorial primitive neuroectodermal tumors (sPNET) using immunohistochemistry. JC viral sequences were analyzed in DNA extracted from 33 frozen medulloblastoma and PNET samples using quantitative polymerase chain reaction. p53 expression was detected in 18% of non-anaplastic medulloblastomas, 45% of anaplastic medulloblastomas, 67% of ATRT, and 88% of sPNET. The increased p53 immunoreactivity in anaplastic medulloblastoma, ATRT, and sPNET was statistically significant. Log rank analysis of clinical outcome revealed significantly shorter survival in patients with p53 immunopositive embryonal tumors. No JC virus was identified in the embryonal brain tumor samples, while an endogenous human retrovirus (ERV-3) was readily detected. Immunoreactivity for p53 protein is more common in anaplastic medulloblastomas, ATRT and sPNET than in non-anaplastic tumors, and is associated with worse clinical outcomes. However, JC virus infection is not responsible for increased levels of p53 protein

  8. Presence of anaplastic lymphoma kinase in inflammatory breast cancer.

    Science.gov (United States)

    Robertson, Fredika M; Petricoin Iii, Emanuel F; Van Laere, Steven J; Bertucci, Francois; Chu, Khoi; Fernandez, Sandra V; Mu, Zhaomei; Alpaugh, Katherine; Pei, Jianming; Circo, Rita; Wulfkuhle, Julia; Ye, Zaiming; Boley, Kimberly M; Liu, Hui; Moraes, Ricardo; Zhang, Xuejun; Demaria, Ruggero; Barsky, Sanford H; Sun, Guoxian; Cristofanilli, Massimo

    2013-01-01

    Although Inflammatory Breast Cancer (IBC) is recognized as the most metastatic variant of locally advanced breast cancer, the molecular basis for the distinct clinical presentation and accelerated program of metastasis of IBC is unknown. Reverse phase protein arrays revealed activation of the receptor tyrosine kinase, anaplastic lymphoma kinase (ALK) and biochemically-linked downstream signaling molecules including JAK1/STAT3, AKT, mTor, PDK1, and AMPKβ in pre-clinical models of IBC. To evaluate the clinical relevance of ALK in IBC, analysis of 25 IBC patient tumors using the FDA approved diagnostic test for ALK genetic abnormalities was performed. These studies revealed that 20/25 (80%) had either increased ALK copy number, low level ALK gene amplification, or ALK gene expression, with a prevalence of ALK alterations in basal-like IBC. One of 25 patients was identified as having an EML4-ALK translocation. The generality of gains in ALK copy number in basal-like breast tumors with IBC characteristics was demonstrated by analysis of 479 breast tumors using the TGCA data-base and our newly developed 79 IBC-like gene signature. The small molecule dual tyrosine kinase cMET/ALK inhibitor, Crizotinib (PF-02341066/Xalkori®, Pfizer Inc), induced both cytotoxicity (IC50 = 0.89 μM) and apoptosis, with abrogation of pALK signaling in IBC tumor cells and in FC-IBC01 tumor xenograft model, a new IBC model derived from pleural effusion cells isolated from an ALK(+) IBC patient. Based on these studies, IBC patients are currently being evaluated for the presence of ALK genetic abnormalities and when eligible, are being enrolled into clinical trials evaluating ALK targeted therapeutics. PMID:24102046

  9. Meningiomas with Rhabdoid or Papillary Components : Prognosis and Comparison with Anaplastic Meningiomas.

    Science.gov (United States)

    Kim, Jeong-Kwon; Jung, Tae-Young; Jung, Shin; Lee, Kyung-Hwa; Kim, Seul-Kee; Lee, Eun Jung

    2016-07-01

    Papillary and rhabdoid meningiomas are pathologically World Health Organization (WHO) grade III. Any correlation between clinical prognosis and pathologic component is not clear. We analyzed the prognoses of patients with meningiomas with a rhabdoid or papillary component compared to those of patients with anaplastic meningiomas. From 1994 to June 2013, 14 anaplastic meningiomas, 6 meningiomas with a rhabdoid component, and 5 meningiomas with papillary component were pathologically diagnosed. We analyzed magnetic resonance imaging (MRI) findings, extent of removal, adjuvant treatment, progression-free survival (PFS), overall survival (OS), and pathologic features of 14 anaplastic meningiomas (group A), 5 meningiomas with a predominant (≥50%) papillary or rhabdoid component (group B1), and 6 meningiomas without a predominant (aggressive behavior than group B2 tumors. In group B2 cases, the pathologic findings of non-rhabdoid/papillary portion could be considered for further adjuvant treatment. PMID:27446516

  10. An integrated texton and bag of words classifier for identifying anaplastic medulloblastomas.

    Science.gov (United States)

    Galaro, Joseph; Judkins, Alexander R; Ellison, David; Baccon, Jennifer; Madabhushi, Anant

    2011-01-01

    In this paper we present a combined Bag of Words and texton based classifier for differentiating anaplastic and non-anaplastic medulloblastoma on digitized histopathology. The hypothesis behind this work is that histological image signatures may reflect different levels of aggressiveness of the disease and that texture based approaches can help discriminate between more aggressive and less aggressive phenotypes of medulloblastoma. The bag of words approach attempts to model the occurrence of differently expressed image features. In this work we choose to model the image features via textons which can quantitatively capture and model texture appearance in the images. The texton-based features, obtained via two methods, the Haar Wavelet responses and MR8 filter bank, provide spatial orientation and rotation invariant attributes. Applying these features to the bag of words framework yields textural representations that can be used in conjunction with a classifier (κ-nearest neighbor) or a content based image retrieval system. Over multiple runs of randomized cross validation, a κ-NN classifier in conjunction with Haar wavelets and the texton, bag of words approach yielded a mean classification accuracy of 80, an area under the precision recall curve of 87 and an area under the ROC curve of 83 in distinguishing between anaplastic and non-anaplastic medulloblastomas on a cohort of 36 patient studies. PMID:22255080

  11. Hemorrhagic cerebellar anaplastic glioma appearing 12 years after prophylactic cranial radiotherapy for acute lymphocytic leukemia

    International Nuclear Information System (INIS)

    A radiation-induced cerebellar glioma is extremely rare, and the etiology of such a tumor is unknown. We report a rare case of hemorrhagic cerebellar anaplastic glioma occurring 12 years after prophylactic cranial radiotherapy for acute lymphocytic leukemia. We discuss the etiologies of the radiation-induced hemorrhagic cerebellar glioma as a secondary malignancy after radiotherapy. (author)

  12. Impact of histopathological transformation and overall survival in patients with progressive anaplastic glioma.

    Science.gov (United States)

    Ho, Allen L; Koch, Matthew J; Tanaka, Shota; Eichler, April F; Batchelor, Tracy T; Tanboon, Jantima; Louis, David N; Cahill, Daniel P; Chi, Andrew S; Curry, William T

    2016-09-01

    Progression of anaplastic glioma (World Health Organization [WHO] grade III) is typically determined radiographically, and transformation to glioblastoma (GB) (WHO grade IV) is often presumed at that time. However, the frequency of actual histopathologic transformation of anaplastic glioma and the subsequent clinical impact is unclear. To determine these associations, we retrospectively reviewed all anaplastic glioma patients who underwent surgery at our center at first radiographic progression, and we examined the effects of histological diagnosis, clinical history, and molecular factors on transformation rate and survival. We identified 85 anaplastic glioma (39 astrocytoma, 24 oligodendroglioma, 22 oligoastrocytoma), of which 38.8% transformed to GB. Transformation was associated with shorter overall survival (OS) from the time of diagnosis (3.4 vs. 10.9years, p=0.0005) and second surgery (1.0 vs. 3.5years, p<0.0001). Original histologic subtype did not significantly impact the risk of transformation or OS. No other factors, including surgery, adjuvant therapy or molecular markers, significantly affected the risk of transformation. However, mutations in isocitrate dehydrogenase 1 (IDH1) was associated with longer time to progression (median 4.6 vs. 1.4years, p=0.008) and OS (median 10.0 vs. 4.2years, p=0.046). At radiographic progression, tissue diagnosis may be warranted as histologic grade may provide valuable prognostic information and affect therapeutic clinical trial selection criteria for this patient population. PMID:27279154

  13. Non-anaplastic peripheral T-cell lymphoma in children and adolescents--a retrospective analysis of the NHL-BFM study group.

    Science.gov (United States)

    Kontny, Udo; Oschlies, Ilske; Woessmann, Willi; Burkhardt, Birgit; Lisfeld, Jasmin; Salzburg, Janina; Janda, Ales; Attarbaschi, Andishe; Niggli, Felix; Zimmermann, Martin; Reiter, Alfred; Klapper, Wolfram

    2015-03-01

    Mature (peripheral) T-cell lymphoma (PTCL) other than anaplastic large cell lymphoma is a heterogeneous group of diseases and exceedingly rare in children and adolescents. Survival rates range between 46% and 85%. This study reports the disease characteristics, treatment and outcome of all patients with the diagnosis of mature TCL registered in the Berlin-Frankfurt-Munster non-Hodgkin lymphoma database between 1986 and 2012. All diagnoses were centrally reviewed and revised by clinico-pathological correlation according to the criteria of the current World Health Organization classification. Of the 69 patients originally registered as having PTCL, the diagnosis was confirmed in 38 of them. Most patients were treated with an anaplastic large cell lymphoma (ALCL)-like therapy regimen. Patients with PTCL-not otherwise specified comprised the largest group and showed a 5-year event-free survival rate of 61 ± 11%. Patients suffering from Natural Killer/T-cell- and hepatosplenic TCL had the poorest outcome. Our results suggest that the outcomes of children with mature TCL other than ALCL depend on the subtype and are worse than in all other paediatric lymphomas. The clinical experience presented in this largest study on paediatric mature TCL may serve as basis for future collaborative international prospective clinical trials. PMID:25395120

  14. Transformation of p53-positive papillary thyroid carcinoma to anaplastic carcinoma of the liver following postoperative radioactive iodine-131 therapy

    OpenAIRE

    Takeshita, Yumie; Takamura, Toshinari; Minato, Hiroshi; Misu, Hirofumi; Ando, Hitoshi; Yamashita, Tatsuya; IKEDA, HIROKO; Nakanuma, Yasuni; Kaneko, Shuichi

    2008-01-01

    Multiple liver metastases were incidentally detected in the lobe of the liver of an 81-year-old woman following total thyroidectomy and ablative radioactive iodine administration for the treatment of papillary thyroid carcinoma. A biopsy specimen taken from the metastatic liver tumor was histologically diagnosed as anaplastic carcinoma. Immunohistochemical staining for p53 was positive in both the primary tumor and liver biopsy specimens. We considered this to have been caused by anaplastic t...

  15. Radiation-induced spinal cord anaplastic astrocytoma subsequent to radiotherapy for testicular seminoma. Case report

    International Nuclear Information System (INIS)

    A 54-year-old man presented with a very rare case of radiation-induced intramedullary spinal cord anaplastic astrocytoma, which developed 37 years after radiotherapy for testicular seminoma. The patient presented with weakness and numbness of the left lower extremity that had gradually aggravated for 3 months. Magnetic resonance imaging demonstrated an intramedullary mass lesion with syringomyelia at the T9 to T12 levels. Subtotal removal of the tumor was performed using standard microsurgical technique. Histological examination revealed anaplastic astrocytoma. Although radiotherapy was seriously considered, chemotherapy was employed as adjuvant therapy considering the previous treatment. Although his neurological status improved transiently after surgery, relentless neurological decline occurred and resulted in death 9 months following surgery. Considering that subtotal removal of the tumor and chemotherapy had little influence on the quality of life and the length of survival in our case, cordectomy may be the optimum treatment for patients with radiation-induced spinal intramedullary malignant astrocytoma. (author)

  16. Acute Hydrocephalus due to Secondary Leptomeningeal Dissemination of an Anaplastic Oligodendroglioma

    OpenAIRE

    Friederike Knerlich-Lukoschus; Heinz-Herrmann Hugo; Stark, Andreas M.; H. Maximilian Mehdorn

    2009-01-01

    Secondary leptomeningeal dissemination of oligodendroglioma is very rare. We report the case of a 38-year-old Caucasian male who presented with acute hydrocephalus. 8 months before, the patient had undergone craniotomy for right frontal anaplastic oligodendroglioma, WHO grade III. By that time, there was no evidence of tumor dissemination. MRI now ruled out local tumor progression but revealed meningeal contrast enhancement along the medulla, the myelon, and the cauda equina. Repeated lumbar ...

  17. Development of anaplastic Wilms tumor and subsequent relapse in a child with diaphanospondylodysostosis.

    Science.gov (United States)

    Tasian, Sarah K; Kim, Grace E; Miniati, Douglas N; DuBois, Steven G

    2012-10-01

    Diaphanospondylodysostosis (DSD) is a rare skeletal dysplasia syndrome resulting from disordered mesenchymal differentiation. Children with DSD generally die in utero or during the first month of life from severe thoracic insufficiency syndrome. An association of DSD with nephroblastomatosis has been observed, but the natural history of such nephroblastomatosis remains poorly characterized due to the rarity of the underlying condition. We describe a patient with DSD who developed bilateral hyperplastic nephroblastomatosis that ultimately evolved into therapy-resistant anaplastic Wilms tumor (nephroblastoma). PMID:22469945

  18. COMBINED CHEMOTHERAPY INCLUDING PROCARBAZINE (NATULAN IN THE TREATMENT OF ANAPLASTIC OLIGODENDROGLIOMAS

    Directory of Open Access Journals (Sweden)

    D. R. Naskhletashvili

    2012-01-01

    Full Text Available Our investigation has demonstrated the high efficiency of combined chemotherapy (CT including procarbazine + lomustine or procarbazine + lomustine + vincristine in patients with anaplastic oligodendrogliomas. Postoperative CT has been recently recommended for patients with deletion of chromosomes 1p and 19q, by taking into account the good prognosis of a therapeutic effect, better parameters of time till progression in this patient group, and a risk for cognitive impairments after brain radiotherapy.

  19. AT-36PANOBINOSTAT IN COMBINATION WITH BEVACIZUMAB FOR RECURRENT GLIOBLASTOMA AND ANAPLASTIC GLIOMA

    OpenAIRE

    Lee, Eudocia; Reardon, David; Schiff, David; Drappatz, Jan; Muzikansky, Alona; Grimm, Sean; Norden, Andrew; Nayak, Lakshmi; Beroukhim, Rameen; Rinne, Mikael; Chi, Andrew; Batchelor, Tracy; Hempfling, Kelly; McCluskey, Christine; Smith, Katrina

    2014-01-01

    Bevacizumab is frequently used to treat recurrent high-grade gliomas, but responses are generally not durable. Panobinostat is a histone deacetylase inhibitor with anti-neoplastic and anti-angiogenic effects in glioma models and may work synergistically with bevacizumab. We conducted a multicenter phase II trial of panobinostat in combination with bevacizumab. Two cohorts were enrolled: one with recurrent glioblastoma (GBM) as the primary study and one with recurrent anaplastic glioma (AG) as...

  20. A Time-Resolved Luminescence Biosensor Assay for Anaplastic Lymphoma Kinase (ALK) Activity†

    OpenAIRE

    Cui, Wei; Parker, Laurie L.

    2014-01-01

    A novel time-resolved luminescence biosensor assay for anaplastic lymphoma kinase (ALK) was developed. We used a straightforward strategy to modify a known ALK substrate into a peptide biosensor that can accommodate terbium luminescence sensitization upon its phosphorylation by ALK. Since this strategy is generalizable, this high-throughput screening compatible assay serves as an example for development of other kinase assays that employ terbium luminescence as a read-out.

  1. A case of adult onset medulloblastoma during maintenance chemotherapy for anaplastic astrocytoma one year after radiotherapy.

    Science.gov (United States)

    Takeshi, Nishimoto; Kazuhiko, Sugiyama; Koji, Iida; Toshikazu, Hidaka; Kaoru, Kurisu

    2013-01-01

    Multiple primitive intracranial tumors with different histological characteristics are uncommon. Although coexistence of a medulloblastoma with glial tumors has been reported in children, medulloblastoma is rarely found in adults, especially those older than 40 years of age. We present an extremely rare case of a medulloblastoma developing in a 40-year-old male undergoing maintenance chemotherapy for anaplastic astrocytoma for 21 months after radiotherapy. Initially, he complained of intractable epilepsy characterized by complex partial seizures. Magnetic resonance imaging (MRI) revealed a slightly enhanced mass lesion in the left insula region. He underwent subtotal removal of the tumor and it was histologically diagnosed as anaplastic astrocytoma. After 19 months of treatment with temozolomide (TMZ) and radiotherapy, he presented with vertigo and headache. A homogeneously enhanced mass had developed in the left cerebellar hemisphere. He received gross total resection of the second tumor, pathologically diagnosed as medulloblastoma. In conclusion, this is the first case report of an adult medulloblastoma coexisting with anaplastic astrocytoma. PMID:24101275

  2. Anaplastic transformation of metastatic papillary thyroid carcinoma at shoulder mimicking soft tissue sarcoma

    Directory of Open Access Journals (Sweden)

    Seema Kaushal

    2011-01-01

    Full Text Available A 52-year-old woman presented with fracture upper end of the left humerus after trivial trauma and aspiration cytology from the lytic lesion in the upper humerus seen on X-ray revealed a metastatic papillary carcinoma from the thyroid. Total thyroidectomy confirmed the papillary carcinoma thyroid. Post-operatively, she was given radioactive iodine (I-131 ablation therapy for 8 years and was asymptomatic during this period; however, for the last 1 year, she has been complaining of swelling in the shoulder, which did not respond to palliative radiotherapy and rapidly increased in size. Disarticulation of the shoulder joint was performed, which showed anaplastic carcinoma on histopathological examination. Anaplastic transformation of papillary carcinoma at the metastatic sites is well documented in the literature and is rare. However, the same has not been reported at the shoulder and from India before. Although soft tissue sarcomas are most common at this site, however, the possibility of anaplastic transformation should be kept in the differential diagnosis of rapidly enlarging painful mass in a known case of metastatic thyroid carcinoma to prevent misdiagnosis.

  3. Successful Treatment in a Child with Anaplastic Large Cell Lymphoma and Coexistence of Pulmonary Tuberculosis

    OpenAIRE

    Katerina Strantzia; Maria Varvoutsi; Despina Bouhoutsou; Maria Tsolia; Apostolos Pourtsidis; Dimitrios Doganis; Margarita Baka; Helen Kosmidis

    2013-01-01

    A 13-year-old girl was admitted to our department with a history of severe pain of her left axilla and fever. On physical examination, a block of lymph nodes in her left axilla, diffuse papular rash, and red-violet swelling of her supraclavicular and subclavian region were noted. Imaging investigations revealed left axillar and supraclavicular lymphadenopathy and a small nodular shade in the upper lobe of her left lung. A biopsy from an axillary lymph node established the diagnosis of anaplas...

  4. Convergent mutations and kinase fusions lead to oncogenic STAT3 activation in anaplastic large cell lymphoma.

    Science.gov (United States)

    Crescenzo, Ramona; Abate, Francesco; Lasorsa, Elena; Tabbo', Fabrizio; Gaudiano, Marcello; Chiesa, Nicoletta; Di Giacomo, Filomena; Spaccarotella, Elisa; Barbarossa, Luigi; Ercole, Elisabetta; Todaro, Maria; Boi, Michela; Acquaviva, Andrea; Ficarra, Elisa; Novero, Domenico; Rinaldi, Andrea; Tousseyn, Thomas; Rosenwald, Andreas; Kenner, Lukas; Cerroni, Lorenzo; Tzankov, Alexander; Ponzoni, Maurilio; Paulli, Marco; Weisenburger, Dennis; Chan, Wing C; Iqbal, Javeed; Piris, Miguel A; Zamo', Alberto; Ciardullo, Carmela; Rossi, Davide; Gaidano, Gianluca; Pileri, Stefano; Tiacci, Enrico; Falini, Brunangelo; Shultz, Leonard D; Mevellec, Laurence; Vialard, Jorge E; Piva, Roberto; Bertoni, Francesco; Rabadan, Raul; Inghirami, Giorgio

    2015-04-13

    A systematic characterization of the genetic alterations driving ALCLs has not been performed. By integrating massive sequencing strategies, we provide a comprehensive characterization of driver genetic alterations (somatic point mutations, copy number alterations, and gene fusions) in ALK(-) ALCLs. We identified activating mutations of JAK1 and/or STAT3 genes in ∼20% of 88 [corrected] ALK(-) ALCLs and demonstrated that 38% of systemic ALK(-) ALCLs displayed double lesions. Recurrent chimeras combining a transcription factor (NFkB2 or NCOR2) with a tyrosine kinase (ROS1 or TYK2) were also discovered in WT JAK1/STAT3 ALK(-) ALCL. All these aberrations lead to the constitutive activation of the JAK/STAT3 pathway, which was proved oncogenic. Consistently, JAK/STAT3 pathway inhibition impaired cell growth in vitro and in vivo. PMID:25873174

  5. Breast Implant–associated Anaplastic Large Cell Lymphoma: Updated Results from a Structured Expert Consultation Process

    Directory of Open Access Journals (Sweden)

    Benjamin Kim, MD, MPhil

    2015-01-01

    Conclusions: Our assessment yielded consistent results on a number of key, incompletely addressed issues regarding BIA-ALCL, but additional research is needed to support these statement ratings and enhance our understanding of the biology, treatment, and outcomes associated with this disease.

  6. P-glycoprotein Mediates Ceritinib Resistance in Anaplastic Lymphoma Kinase-rearranged Non-small Cell Lung Cancer

    Science.gov (United States)

    Katayama, Ryohei; Sakashita, Takuya; Yanagitani, Noriko; Ninomiya, Hironori; Horiike, Atsushi; Friboulet, Luc; Gainor, Justin F.; Motoi, Noriko; Dobashi, Akito; Sakata, Seiji; Tambo, Yuichi; Kitazono, Satoru; Sato, Shigeo; Koike, Sumie; John Iafrate, A.; Mino-Kenudson, Mari; Ishikawa, Yuichi; Shaw, Alice T.; Engelman, Jeffrey A.; Takeuchi, Kengo; Nishio, Makoto; Fujita, Naoya

    2015-01-01

    The anaplastic lymphoma kinase (ALK) fusion oncogene is observed in 3%–5% of non-small cell lung cancer (NSCLC). Crizotinib and ceritinib, a next-generation ALK tyrosine kinase inhibitor (TKI) active against crizotinib-refractory patients, are clinically available for the treatment of ALK-rearranged NSCLC patients, and multiple next-generation ALK-TKIs are currently under clinical evaluation. These ALK-TKIs exhibit robust clinical activity in ALK-rearranged NSCLC patients; however, the emergence of ALK-TKI resistance restricts the therapeutic effect. To date, various secondary mutations or bypass pathway activation-mediated resistance have been identified, but large parts of the resistance mechanism are yet to be identified. Here, we report the discovery of p-glycoprotein (P-gp/ABCB1) overexpression as a ceritinib resistance mechanism in ALK-rearranged NSCLC patients. P-gp exported ceritinib and its overexpression conferred ceritinib and crizotinib resistance, but not to PF-06463922 or alectinib, which are next-generation ALK inhibitors. Knockdown of ABCB1 or P-gp inhibitors sensitizes the patient-derived cancer cells to ceritinib, in vitro and in vivo. P-gp overexpression was identified in three out of 11 cases with in ALK-rearranged crizotinib or ceritinib resistant NSCLC patients. Our study suggests that alectinib, PF-06463922, or P-gp inhibitor with ceritinib could overcome the ceritinib or crizotinib resistance mediated by P-gp overexpression. PMID:26870817

  7. P-glycoprotein Mediates Ceritinib Resistance in Anaplastic Lymphoma Kinase-rearranged Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Ryohei Katayama

    2016-01-01

    Full Text Available The anaplastic lymphoma kinase (ALK fusion oncogene is observed in 3%–5% of non-small cell lung cancer (NSCLC. Crizotinib and ceritinib, a next-generation ALK tyrosine kinase inhibitor (TKI active against crizotinib-refractory patients, are clinically available for the treatment of ALK-rearranged NSCLC patients, and multiple next-generation ALK-TKIs are currently under clinical evaluation. These ALK-TKIs exhibit robust clinical activity in ALK-rearranged NSCLC patients; however, the emergence of ALK-TKI resistance restricts the therapeutic effect. To date, various secondary mutations or bypass pathway activation-mediated resistance have been identified, but large parts of the resistance mechanism are yet to be identified. Here, we report the discovery of p-glycoprotein (P-gp/ABCB1 overexpression as a ceritinib resistance mechanism in ALK-rearranged NSCLC patients. P-gp exported ceritinib and its overexpression conferred ceritinib and crizotinib resistance, but not to PF-06463922 or alectinib, which are next-generation ALK inhibitors. Knockdown of ABCB1 or P-gp inhibitors sensitizes the patient-derived cancer cells to ceritinib, in vitro and in vivo. P-gp overexpression was identified in three out of 11 cases with in ALK-rearranged crizotinib or ceritinib resistant NSCLC patients. Our study suggests that alectinib, PF-06463922, or P-gp inhibitor with ceritinib could overcome the ceritinib or crizotinib resistance mediated by P-gp overexpression.

  8. Cytotoxic effects of Gemcitabine-loaded liposomes in human anaplastic thyroid carcinoma cells

    Directory of Open Access Journals (Sweden)

    Rotiroti Domenicoantonio

    2004-09-01

    Full Text Available Abstract Background Identification of effective systemic antineoplastic drugs against anaplastic thyroid carcinomas has particularly important implications. In fact, the efficacy of the chemotherapeutic agents presently used in these tumours, is strongly limited by their low therapeutic index. Methods In this study gemcitabine was entrapped within a pegylated liposomal delivery system to improve the drug antitumoral activity, thus exploiting the possibility to reduce doses to be administered in cancer therapy. The cytotoxic effects of free or liposome-entrapped gemcitabine was evaluated against a human thyroid tumour cell line. ARO cells, derived from a thyroid anaplastic carcinoma, were exposed to different concentrations of the drug. Liposomes formulations were made up of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine/cholesterol/1,2-distearoyl-sn-glycero-3-phosphoethanolamine-MPEG (8:3:1 molar ratio. Cell viability was assessed by both trypan bleu dye exclusion assay and fluorimetric analysis of cell DNA content. Results A cytotoxic effect of free gemcitabine was present only after 72 h incubation (ARO cell mortality increased of approximately 4 fold over control at 1 μM, 7 fold at 100 μM. When gemcitabine was encapsulated in liposomes, a significant effect was observed by using lower concentrations of the drug (increased cell mortality of 2.4 fold vs. control at 0.3 μM and earlier exposure time (24 h. Conclusion These findings show that, in vitro against human thyroid cancer cells, the gemcitabine incorporation within liposomes enhances the drug cytotoxic effect with respect to free gemcitabine, thus suggesting a more effective drug uptake inside the cells. This may allow the use of new formulations with lower dosages (side effect free for the treatment of anaplastic human thyroid tumours.

  9. Cytotoxic effects of Gemcitabine-loaded liposomes in human anaplastic thyroid carcinoma cells

    International Nuclear Information System (INIS)

    Identification of effective systemic antineoplastic drugs against anaplastic thyroid carcinomas has particularly important implications. In fact, the efficacy of the chemotherapeutic agents presently used in these tumours, is strongly limited by their low therapeutic index. In this study gemcitabine was entrapped within a pegylated liposomal delivery system to improve the drug antitumoral activity, thus exploiting the possibility to reduce doses to be administered in cancer therapy. The cytotoxic effects of free or liposome-entrapped gemcitabine was evaluated against a human thyroid tumour cell line. ARO cells, derived from a thyroid anaplastic carcinoma, were exposed to different concentrations of the drug. Liposomes formulations were made up of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine/cholesterol/ 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-MPEG (8:3:1 molar ratio). Cell viability was assessed by both trypan bleu dye exclusion assay and fluorimetric analysis of cell DNA content. A cytotoxic effect of free gemcitabine was present only after 72 h incubation (ARO cell mortality increased of approximately 4 fold over control at 1 μM, 7 fold at 100 μM). When gemcitabine was encapsulated in liposomes, a significant effect was observed by using lower concentrations of the drug (increased cell mortality of 2.4 fold vs. control at 0.3 μM) and earlier exposure time (24 h). These findings show that, in vitro against human thyroid cancer cells, the gemcitabine incorporation within liposomes enhances the drug cytotoxic effect with respect to free gemcitabine, thus suggesting a more effective drug uptake inside the cells. This may allow the use of new formulations with lower dosages (side effect free) for the treatment of anaplastic human thyroid tumours

  10. FDG PET staging compared to C.T. in children with Hodgkin's disease or anaplastic lymphoma

    International Nuclear Information System (INIS)

    The accuracy of initial staging in Hodgkin's disease and anaplastic lymphoma is very important since treatment depends on the initial staging disease. An error of assessment can have serious consequences on evolution and survival. To judge PET scan performances initial staging was done on our patients by both conventional imaging and PET scan. Methods: 21 children (10 girls, 11 boys), median age 14,9 years (8 to 22) had a PET scan for the initial staging (17 Hodgkin's disease, 4 anaplastic lymphomas). Conventional staging for imaging included: Thorax x-ray, thorax and abdomen C.T., abdominal echography, and also two bone marrow biopsies. Others exams were done in accordance with special clinical data. PET scan was done on a C PET scan ADAC one hour after IV injection of 2 MBq/Kg of 18 FDG. C.T. and PET scan images were revised blindly and separately by radiologist and nuclearist with no knowledge of clinical data. Results: the staging by C.I. and PET scan were concordant in 84% of cases. In 16% of cases PET scan displayed localisation not seen by C.I., particularly bone lesions. The staging changed grading status from stage III to stage IV. The clinical cases will be presented. PET scan upgrading were confirmed by resonance imaging or bone scintigraphy. The change of stage led in each child an intensification of chemotherapy (6 courses instead of 4). Conclusion: FDG PET is a useful diagnostic tool in children with Hodgkin's disease or anaplastic lymphoma to achieve with a single exam an accurate staging allowing to choose the best treatment

  11. THE ASSOCIATION OF WELL-DIFFERENTIATED THYROID-CARCINOMA WITH INSULAR OR ANAPLASTIC THYROID-CARCINOMA - EVIDENCE FOR DEDIFFERENTIATION IN TUMOR PROGRESSION

    NARCIS (Netherlands)

    van der Laan, Bernard F.A.M.; FREEMAN, JL; TSANG, RW; ASA, SL

    1993-01-01

    The sequence of tumorigenesis in the thyroid is unclear. It has been proposed that anaplastic carcinomas of the thyroid develop by dedifferentiation in pre-existing differentiated carcinomas. We reviewed all anaplastic and insular (poorly differentiated) thyroid carcinomas in a consultation practice

  12. Emergency total thyroidectomy for bleeding anaplastic thyroid carcinoma: A viable option for palliation

    Directory of Open Access Journals (Sweden)

    Sunil Kumar

    2011-01-01

    Full Text Available Anaplastic thyroid carcinoma (ATC is a rare and highly aggressive thyroid neoplasm. Bleeding from tumor is an uncommon, but potentially life-threatening complication requiring sophisticated intervention facilities which are not usually available at odd hours in emergency. We report the case of a 45-year-old woman who presented with exsanguinating hemorrhage from ATC and was treated by emergency total thyroidectomy. The patient is well three months postoperatively. Emergency total thyroidectomy is a viable option for palliation in ATC presenting with bleeding.

  13. A significant response to sunitinib in a patient with anaplastic thyroid carcinoma

    Directory of Open Access Journals (Sweden)

    Enrique Grande

    2013-01-01

    Full Text Available Anaplastic thyroid cancer (ATC is a rare disease with an incidence of less than three cases per million of habitants in western countries. ATC accounts for 1-10% of all tumors derived from the thyroid gland. Classic chemotherapy approach based on platinum and anthracyclines regimens have been considered standard for the last decades. Novel multitarget agents have shown promising responses; however, no positive randomized clinical trials are available up to now. To our knowledge, the case we are presenting here is the first reported case showing clinical and visual activity using sunitinib as a salvage treatment in an ATC patient who was not fit to receive systemic chemotherapy treatment.

  14. Abnormal number cell division of human thyroid anaplastic carcinoma cell line, SW 1736

    Directory of Open Access Journals (Sweden)

    Keiichi Ikeda

    2015-12-01

    Full Text Available Cell division, during which a mother cell usually divides into two daughter cells during one cell cycle, is the most important physiological event of cell biology. We observed one-to-four cell division during imaging of live SW1736 human thyroid anaplastic carcinoma cells transfected with a plasmid expressing the hybrid protein of green fluorescent protein and histone 2B (plasmid eGFP-H2B. Analysis of the images revealed a mother cell divided into four daughter cells. And one of the abnormally divided daughter cells subsequently formed a dinucleate cell.

  15. Investigation of the results of therapy of anaplastic thyroid gland carcinomas

    International Nuclear Information System (INIS)

    The results of the treatment of 28 patients with an anaplastic thyroid gland carcinoma are investigated, to see whether an optimal therapy is indicated. The execution of an operation before radiotherapy does not appear to improve the prognosis (statistically this conclusion is not wholly justified). The presence of metastases at the beginning of the therapy gave rise to a worse prognosis than the absence of metastases. The combination treatment of chemotherapy and either surgery or radiotherapy was only applied to two patients so no conclusions can be made about its benefit. (C.F.)

  16. Absence of anaplastic lymphoma kinase-1 expression in inflammatory myofibroblastic tumors of the central nervous system: Does it signify a different nosologic entity from its systemic counterpart?

    Directory of Open Access Journals (Sweden)

    Aparna Govindan

    2014-01-01

    Full Text Available Background and Aim: Inflammatory myofibroblastic tumors (IMFTs are uncommon neoplasms of the central nervous system (CNS of intermediate grade biologic potential. Anaplastic lymphoma kinase (ALK-1, a diagnostic marker of anaplastic large cell lymphoma, is also expressed in a subset of IMFTs and appears to have prognostic significance. Though, few studies have evaluated expression of ALK-1 in IMFTs of the CNS. This retrospective study was undertaken to evaluate the expression of ALK-1 expression in IMFT of CNS by immunohistochemistry and correlate with the clinical, radiological and pathologic features. Materials and Methods: Five cases diagnosed as IMFT/inflammatory pseudotumour/plasma cell granuloma, diagnosed in CNS over 10 year period (1998-2007 were retrieved from the archives of Department of Neuropathology of a tertiary referralcenter. The clinical profile and imaging features were collected from the case records. Hematoxylin and eosin stained sections were reviewed with immunohistochemistry for smooth muscle actin (SMA, vimentin, desmin, ALK-1, p53, MIB-1, CD68, leukocyte common antigen, CD3, and CD20. Results: All five cases of IMFTs presented as dural-based space occupying or en-plaque lesions. Histologically, four cases had combined plasma cell granuloma-fibrous histiocytoma morphology, and one had fibrous histiocytoma-like morphology. Immunohistochemically, SMA was strongly positive in spindle cell component of the tumors confirming diagnosis. ALK-1 expression could not be detected by immunohistochemistry in any of the cases. Conclusion: Further studies analyzing ALK-1 gene mutation and rearrangements are required to determine pathogenetic role, if any, in CNS IMFTs.

  17. Molecular analysis of anaplastic oligodendroglial tumors in a prospective randomized study: A report from EORTC study 26951

    NARCIS (Netherlands)

    M.C.M. Kouwenhoven (Mathilde); T.S. Gorlia (Thierry); J.M. Kros (Johan); A. Ibdaih (Ahmed); A. Brandes (Alba); J.E.C. Bromberg (Jacolien); K. Mokhtari (Karima); S.G. van Duinen (Sjoerd); J.L.J.M. Teepen; P. Wesseling (Pieter); F. Vandenbos (Fanny); W. Grisold (Wolfgang); L. Sipos (László); R.O. Mirimanoff; C.J. Vecht (Charles); A. Allgeier (Anouk); D. Lacombe (Denis); M.J. van den Bent (Martin)

    2009-01-01

    textabstractRecent studies have shown that the clinical outcome of anaplastic oligodendroglial tumors is variable, but also that the histological diagnosis is subject to interobserver variation. We investigated whether the assessment of 1p/19q codeletion, polysomy of chromosome 7, epidermal growth f

  18. Detection of novel and potentially actionable anaplastic lymphoma kinase (ALK) rearrangement in colorectal adenocarcinoma by immunohistochemistry screening

    OpenAIRE

    Lee, Jeeyun; Kim, Hee Cheol; Hong, Jung Yong; Wang, Kai; Kim, Sun Young; Jang, Jiryeon; Kim, Seung Tae; Park, Joon Oh; Lim, Ho Yeong; Kang, Won Ki; Park, Young Suk; Lee, Jiyun; Lee, Woo Yong; Park, Yoon Ah; Huh, Jung Wook

    2015-01-01

    Purpose Anaplastic lymphoma kinase (ALK) rearrangement has been detected in colorectal carcinoma (CRC) using advanced molecular diagnostics tests including exon scanning, fluorescence in situ hybridization (FISH), and next generation sequencing (NGS). We investigated if immunohistochemistry (IHC) can be used to detect ALK rearrangement in gastrointestinal malignancies. Experimental designs Tissue microarrays (TMAs) from consecutive gastric carcinoma (GC) and CRC patients who underwent surgica...

  19. Molecular analysis of anaplastic oligodendroglial tumors in a prospective randomized study: A report from EORTC study 26951.

    Science.gov (United States)

    Kouwenhoven, Mathilde C M; Gorlia, Thierry; Kros, Johan M; Ibdaih, Ahmed; Brandes, Alba A; Bromberg, Jacolien E C; Mokhtari, Karima; van Duinen, Sjoerd G; Teepen, Johannes L; Wesseling, Pieter; Vandenbos, Fanny; Grisold, Wolfgang; Sipos, László; Mirimanoff, Rene; Vecht, Charles J; Allgeier, Anouk; Lacombe, Denis; van den Bent, Martin J

    2009-12-01

    Recent studies have shown that the clinical outcome of anaplastic oligodendroglial tumors is variable, but also that the histological diagnosis is subject to interobserver variation. We investigated whether the assessment of 1p/19q codeletion, polysomy of chromosome 7, epidermal growth factor receptor (EGFR) gene amplification (EGFR(amp)), and loss of chromosome 10 or 10q offers additional prognostic information to the histological diagnosis and would allow molecular subtyping. For this study, we used the clinical data and tumor samples of the patients included in multicenter prospective phase III European Organisation for Research and Treatment of Cancer (EORTC) study 26951 on the effects of adjuvant procarbazine, chloroethyl cyclohexylnitrosourea (lomustine), and vincristine chemotherapy in anaplastic oligodendroglial tumors. Fluorescence in situ hybridization was used to assess copy number aberrations of chromosome 1p, 19q, 7, 10, and 10q and EGFR. Three different analyses were performed: on all included patients based on local pathology diagnosis, on the patients with confirmed anaplastic oligodendroglial tumors on central pathology review, and on this latter group but after excluding anaplastic oligoastrocytoma (AOA) with necrosis. As a reference set for glioblastoma multiforme (GBM), patients from the prospective randomized phase III study on GBM (EORTC 26981) were used as a benchmark. In 257 of 368 patients, central pathology review confirmed the presence of an anaplastic oligodendroglial tumor. Tumors with combined 1p and 19q loss (1p(loss)19q(loss)) were histopathologically diagnosed as anaplastic oligodendroglioma, were more frequently located in the frontal lobe, and had a better outcome. Anaplastic oligodendroglial tumors with EGFR(amp) were more frequently AOA, were more often localized outside the frontal lobe, and had a survival similar to that for GBM. Survival of patients with AOA harboring necrosis was in a similar range as for GBM, while patients

  20. Impact of 1p/19q Codeletion and Histology on Outcomes of Anaplastic Gliomas Treated With Radiation Therapy and Temozolomide

    Energy Technology Data Exchange (ETDEWEB)

    Speirs, Christina K.; Simpson, Joseph R.; Robinson, Clifford G.; DeWees, Todd A. [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Tran, David D.; Linette, Gerry [Department of Medicine, Division of Medical Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Chicoine, Michael R.; Dacey, Ralph G.; Rich, Keith M.; Dowling, Joshua L.; Leuthardt, Eric C.; Zipfel, Gregory J.; Kim, Albert H. [Department of Neurosurgery, Washington University School of Medicine, St. Louis, Missouri (United States); Huang, Jiayi, E-mail: jhuang@radonc.wustl.edu [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States)

    2015-02-01

    Purpose: Anaplastic gliomas represent a heterogeneous group of primary high-grade brain tumors, and the optimal postoperative treatment remains controversial. In this report, we present our institutional data on the clinical outcomes of radiation therapy (RT) plus temozolomide (RT + TMZ) for anaplastic gliomas, stratified by histology and 1p/19q codeletion. Methods and Materials: A single-institution retrospective review was conducted of patients with supratentorial anaplastic oligodendroglioma (AO), mixed anaplastic oligoastrocytoma (AOA), and anaplastic astrocytoma (AA). After surgery, RT was delivered at a median total dose of 60 Gy (range, 31.6-63 Gy) in daily fractions. All patients received standard concurrent TMZ, with or without adjuvant TMZ. Histological/molecular subtypes were defined as codeleted AO/AOA, non-codeleted AO/AOA, and AA. Results: From 2000 to 2012, 111 cases met study criteria and were evaluable. Codeleted AO/AOA had superior overall survival (OS) to non-codeleted AO/AOA (91% vs 68% at 5 years, respectively, P=.02), whereas progression-free survival (PFS) was not significantly different (70% vs 46% at 5 years, respectively, P=.10). AA had inferior OS to non-codeleted AO/AOA (37% vs 68% at 5 years, respectively, P=.007) and inferior PFS (27% vs 46%, respectively, P=.03). On multivariate analysis, age, performance status, and histological or molecular subtype were independent predictors for both PFS and OS. Compared to historical controls, RT + TMZ provided comparable OS to RT with procarbazine, lomustine, and vincristine (RT + PCV) for codeleted AO/AOA, superior OS to RT alone for non-codeleted AO/AOA, and similar OS to RT alone for AA. Conclusions: RT + TMZ may be a promising treatment for both codeleted and non-codeleted AO/AOA, but its role for AA remains unclear.

  1. Impact of 1p/19q Codeletion and Histology on Outcomes of Anaplastic Gliomas Treated With Radiation Therapy and Temozolomide

    International Nuclear Information System (INIS)

    Purpose: Anaplastic gliomas represent a heterogeneous group of primary high-grade brain tumors, and the optimal postoperative treatment remains controversial. In this report, we present our institutional data on the clinical outcomes of radiation therapy (RT) plus temozolomide (RT + TMZ) for anaplastic gliomas, stratified by histology and 1p/19q codeletion. Methods and Materials: A single-institution retrospective review was conducted of patients with supratentorial anaplastic oligodendroglioma (AO), mixed anaplastic oligoastrocytoma (AOA), and anaplastic astrocytoma (AA). After surgery, RT was delivered at a median total dose of 60 Gy (range, 31.6-63 Gy) in daily fractions. All patients received standard concurrent TMZ, with or without adjuvant TMZ. Histological/molecular subtypes were defined as codeleted AO/AOA, non-codeleted AO/AOA, and AA. Results: From 2000 to 2012, 111 cases met study criteria and were evaluable. Codeleted AO/AOA had superior overall survival (OS) to non-codeleted AO/AOA (91% vs 68% at 5 years, respectively, P=.02), whereas progression-free survival (PFS) was not significantly different (70% vs 46% at 5 years, respectively, P=.10). AA had inferior OS to non-codeleted AO/AOA (37% vs 68% at 5 years, respectively, P=.007) and inferior PFS (27% vs 46%, respectively, P=.03). On multivariate analysis, age, performance status, and histological or molecular subtype were independent predictors for both PFS and OS. Compared to historical controls, RT + TMZ provided comparable OS to RT with procarbazine, lomustine, and vincristine (RT + PCV) for codeleted AO/AOA, superior OS to RT alone for non-codeleted AO/AOA, and similar OS to RT alone for AA. Conclusions: RT + TMZ may be a promising treatment for both codeleted and non-codeleted AO/AOA, but its role for AA remains unclear

  2. Small cell anaplastic carcinoma of primary lung tumor in a miniature schnauzer dog

    International Nuclear Information System (INIS)

    A seven-year-old male, an intact miniature Schnauzer dog with history of vomiting, abdominal distention, anorexia, and dyspnea was referred for further evaluation and treatment. Thoracic radiographs showed the well marginated solitary mass with soft density in the right caudal lung field, and abdominal radiographs showed signs of ascites, such as abdominal distention and moderate serosal detail loss. On ultrasonograph and computed tomograph, it was observed that the mass compressed the caudal vena cava (CVC) and adhered to the heart. Exploratory thoracotomy was performed, and then it was showed that mass adhered heart, CVC, and diaphragm. The mass was fully rejected although adhered part of CVC could not be completely rejected. On histopathological findings, the mass was diagnosed as small-cell anaplastic carcinoma

  3. Chemoradiation for anaplastic oligodendrogliomas: clinical outcomes and prognostic value of molecular markers.

    Science.gov (United States)

    Minniti, Giuseppe; Arcella, Antonella; Scaringi, Claudia; Lanzetta, Gaetano; Di Stefano, Domenica; Scarpino, Stefania; Pace, Andrea; Giangaspero, Felice; Osti, Mattia Falchetto; Enrici, Riccardo Maurizi

    2014-01-01

    Combination of procarbazine, lomustine and vincristine (PCV) with radiation therapy (RT) has been associated with longer survival in patients with anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA), especially in those with chromosome 1p/19q codeletion. We report a multicenter retrospective study of 84 consecutive adult patients with AO and AOA treated with RT plus concomitant and adjuvant temozolomide (TMZ) between February 2004 and January 2011. Correlations between chromosome 1p/19q codeletion, isocitrate dehydrogenase1 (IDH1) mutation, and O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation with survival outcomes have been analyzed. For all 84 patients the median overall survival (OS) and progression-free survival rates were 55.6 and 45.2 months, respectively. Grade 3 or 4 hematological toxicity occurred in 17 % of patients. Chromosome 1p/19q codeletion was detected in 57 %, IDH1 mutation in 63 %, and MGMT promoter methylation in 74 % of evaluable patients. In multivariate analysis the presence of chromosome 1p/19q codeletion was associated with significant survival benefit (median OS 34 months in noncodeleted tumors and not reached in codeleted tumors; HR 0.16, 95 % CI 0.03-0.45; P = 0.005). IDH1 mutation was also of prognostic significance for longer survival (P = 0.001; HR 0.20, 95 % 0.06-0.41), whereas MGMT promoter methylation was only of borderline significance. The study indicates that RT with concomitant and adjuvant TMZ is a relatively safe treatment associated with longer survival in patients with 1p/19q codeleted and IDH1 mutated tumors. Results from ongoing randomized studies will be essential to clarify if RT plus TMZ may provide survival as good as or better than RT combined with PCV for patients with AO and AOA. PMID:24162810

  4. Molecular classification of anaplastic oligodendroglioma using next-generation sequencing: A report of the prospective randomized EORTC Brain Tumor Group 26951 phase III trial

    NARCIS (Netherlands)

    H.J. Dubbink (Erik Jan); P.N. Atmodimedjo; J.M. Kros (Johan); P.J. French (Pim); M. Sanson (Marc); A. Idbaih (Ahmed); P. Wesseling (Pieter); R. Enting (Roelien); W.G.M. Spliet (Wim); C.C. Tijssen (Cees); W.N.M. Dinjens (Winand); T.S. Gorlia (Thierry); M.J. van den Bent (Martin)

    2016-01-01

    textabstractBackground Histopathological diagnosis of diffuse gliomas is subject to interobserver variation and correlates modestly with major prognostic and predictive molecular abnormalities. We investigated a series of patients with locally diagnosed anaplastic oligodendroglial tumors included in

  5. Thirty-nine cases of intracranial hemangiopericytoma and anaplastic hemangiopericytoma: A retrospective review of MRI features and pathological findings

    International Nuclear Information System (INIS)

    Objective: To retrospectively review the imaging features of surgically and pathologically confirmed intracranial hemangiopericytoma and anaplastic hemangiopericytoma. Methods: Thirty-nine cases of surgically and pathologically confirmed hemangiopericytoma and anaplastic hemangiopericytoma were analyzed retrospectively. The MRI features were compared with pathological findings in all cases. Results: Of the 39 cases, 21 were anaplastic hemangiopericytoma (WHO grade III) and the remaining cases were hemangiopericytoma (WHO grade II); all lesions were solitary. MRI of anaplastic hemangiopericytoma showed that 20 cases were lobulated, and nine grew cross-leaf. The lesions showed mixed iso-high-low signal (n = 20) or iso-signal (n = 1) on plain T1WI, and mixed high-low signal (n = 20) or iso-signal (n = 1) on plain T2WI. After contrast injection, marked heterogeneous enhancement was seen in 19 cases. Significant necrosis and cystic changes were seen in 16 cases, and the “dural tail sign” was found in two cases. Ten cases had bony destruction, and 16 showed significant peritumoral edema. In 18 cases of hemangiopericytoma, nine were oval-shaped and three grew cross-leaf. The lesions showed mixed iso-low signal (n = 10) or iso-signal (n = 8) on plain T1WI, and mixed iso-high signal (n = 10) or iso-signal (n = 8) on plain T2WI. After contrast injection, significant uniform enhancement was seen in 10 cases. Significant necrosis and cystic changes were seen in seven cases, and “dural tail sign” was seen in six cases. Two cases had bony destruction. No case showed significant peritumoral edema. Pathological immunohistochemical Ki67 staining showed a concentration of ∼18.4% positive cells in anaplastic hemangiopericytoma, whereas in hemangiopericytoma it was 7.12%. Conclusion: Imaging findings of intracranial anaplastic hemangiopericytoma had more pronounced lobulation, cross-leaf growth tendency, more and easier bleeding, more necrosis, more cystic changes giving

  6. Clonal heterogeneity of small-cell anaplastic carcinoma of the lung demonstrated by flow-cytometric DNA analysis

    DEFF Research Database (Denmark)

    Vindeløv, L L; Hansen, H H; Christensen, I J;

    1980-01-01

    Flow-cytometric DNA analysis yields information on ploidy and proliferative characteristics of a cell population. The analysis was implemented on small-cell anaplastic carcinoma of the lung using a rapid detergent technique for the preparation of fine-needle aspirates for DNA determination and a...... newly developed procedure for storing aspirates at -80 degrees. Thirty-eight different metastases in 30 consecutive patients with small-cell anaplastic carcinoma of the lung were examined with a total of 273 fine-needle aspirations. The results on ploidy are reported in this paper. The degree of...... contamination of the aspirates with normal cells was determined by differential counts. The ratio of the peak channel numbers for the G1 phase of the tumor cells to that of the diploid standard (DNA index) was calculated and used for ploidy identification. Twenty-nine patients were evaluable with respect to DNA...

  7. P-glycoprotein Mediates Ceritinib Resistance in Anaplastic Lymphoma Kinase-rearranged Non-small Cell Lung Cancer

    OpenAIRE

    Ryohei Katayama; Takuya Sakashita; Noriko Yanagitani; Hironori Ninomiya; Atsushi Horiike; Luc Friboulet; Gainor, Justin F.; Noriko Motoi; Akito Dobashi; Seiji Sakata; Yuichi Tambo; Satoru Kitazono; Shigeo Sato; Sumie Koike; John Iafrate, A.

    2015-01-01

    The anaplastic lymphoma kinase (ALK) fusion oncogene is observed in 3%–5% of non-small cell lung cancer (NSCLC). Crizotinib and ceritinib, a next-generation ALK tyrosine kinase inhibitor (TKI) active against crizotinib-refractory patients, are clinically available for the treatment of ALK-rearranged NSCLC patients, and multiple next-generation ALK-TKIs are currently under clinical evaluation. These ALK-TKIs exhibit robust clinical activity in ALK-rearranged NSCLC patients; however, the emerge...

  8. Molecular analysis of anaplastic oligodendroglial tumors in a prospective randomized study: A report from EORTC study 26951

    OpenAIRE

    Kouwenhoven, Mathilde C. M.; Gorlia, Thierry; Kros, Johan M; Ibdaih, Ahmed; Brandes, Alba A.; Bromberg, Jacolien E.C.; Mokhtari, Karima; van Duinen, Sjoerd G.; Teepen, Johannes L.; Wesseling, Pieter; Vandenbos, Fanny; Grisold, Wolfgang; Sipos, László; Mirimanoff, Rene; Vecht, Charles J

    2009-01-01

    Recent studies have shown that the clinical outcome of anaplastic oligodendroglial tumors is variable, but also that the histological diagnosis is subject to interobserver variation. We investigated whether the assessment of 1p/19q codeletion, polysomy of chromosome 7, epidermal growth factor receptor (EGFR) gene amplification (EGFRamp), and loss of chromosome 10 or 10q offers additional prognostic information to the histological diagnosis and would allow molecular subtyping. For this study, ...

  9. An infant with hyperalertness, hyperkinesis, and failure to thrive: a rare diencephalic syndrome due to hypothalamic anaplastic astrocytoma

    OpenAIRE

    Stival, Alessia; Lucchesi, Maurizio; Farina, Silvia; Buccoliero, Anna Maria; Castiglione, Francesca; Genitori, Lorenzo; de Martino, Maurizio; Sardi, Iacopo

    2015-01-01

    Background Diencephalic Syndrome is a rare clinical condition of failure to thrive despite a normal caloric intake, hyperalertness, hyperkinesis, and euphoria usually associated with low-grade hypothalamic astrocytomas. Case presentation We reported an unusual case of diencephalic cachexia due to hypothalamic anaplastic astrocytoma (WHO-grade III). Baseline endocrine function evaluation was performed in this patient before surgery. After histological diagnosis, he enrolled to a chemotherapy p...

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

    Directory of Open Access Journals (Sweden)

    Maher Kurdi

    2014-01-01

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

  11. Iodide uptake in human anaplastic thyroid carcinoma cells after transfer of the human thyroid peroxidase gene

    International Nuclear Information System (INIS)

    Human thyroperoxidase (hTPO) is critical for the accumulation of iodide in thyroid tissues. Poorly differentiated and anaplastic thyroid tumours which lack thyroid-specific gene expression fail to accumulate iodide and, therefore, do not respond to iodine-131 therapy. We consequently investigated whether transfer of the hTPO gene is sufficient to restore the iodide-trapping capacity in undifferentiated thyroid and non-thyroid tumour cells. The human anaplastic thyroid carcinoma cell lines C643 and SW1736, the rat Morris hepatoma cell line MH3924A and the rat papillary thyroid carcinoma cell line L2 were used as in vitro model systems. Employing a bicistronic retroviral vector based on the myeloproliferative sarcoma virus for the transfer of the hTPO and the neomycin resistance gene, the C643 cells and SW1736 cells were transfected while the L2 cells and MH3924A cells were infected with retroviral particles. Seven recombinant C643 and seven SW1736 cell lines as well as four recombinant L2 and four MH3924A cell lines were established by neomycin selection. They were studied for hTPO expression using an antibody-based luminescence kit, followed by determination of the enzyme activity in the guaiacol assay and of the iodide uptake capacity in the presence of Na125I. Genetically modified cell lines expressed up to 1,800 times more hTPO as compared to wild type tumour cells. The level of hTPO expression varied significantly between individual neomycin-resistant cell lines, suggesting that the recombinant retroviral DNA was integrated at different sites of the cellular genome. The accumulation of iodide, however, was not significantly enhanced in individual recombinant cell lines, irrespective of low or high hTPO expression. Moreover, there was no correlation between hTPO expression and enzyme activity in individual cell lines. The transduction of the hTPO gene per se is not sufficient to restore iodide trapping in non-iodide-concentrating tumour cells. Future studies

  12. Testing for anaplastic lymphoma kinase rearrangement to target crizotinib therapy: oncology, pathology and health economic perspectives.

    Science.gov (United States)

    Lee, James A; Bubendorf, Lukas; Stahel, Rolf; Peters, Solange

    2013-05-01

    Crizotinib is a first-in-class oral anaplastic lymphoma kinase (ALK) inhibitor targeting ALK-rearranged non-small-cell lung cancer. The therapy was approved by the US FDA in August 2011 and received conditional marketing approval by the European Commission in October 2012 for advanced non-small-cell lung cancer. A break-apart FISH-based assay was jointly approved with crizotinib by the FDA. This assay and an immunohistochemistry assay that uses a D5F3 rabbit monoclonal primary antibody were also approved for marketing in Europe in October 2012. While ALK rearrangement has relatively low prevalence, a clinical benefit is exhibited in more than 85% of patients with median progression-free survival of 8-10 months. In this article, the authors summarize the therapy and alternative test strategies for identifying patients who are likely to respond to therapy, including key issues for effective and efficient testing. The key economic considerations regarding the joint companion diagnostic and therapy are also presented. Given the observed clinical benefit and relatively high cost of crizotinib therapy, companion diagnostics should be evaluated relative to response to therapy versus correlation alone whenever possible, and both high inter-rater reliability and external quality assessment programs are warranted. PMID:23617353

  13. Multidisciplinaly total-cell-kill treatment of bronchogenic small cell anaplastic carcinoma

    International Nuclear Information System (INIS)

    Survival time of the patients with bronchogenic small cell anaplastic cancer was studied. Combined treatment with six-drug combination chemotherapy ''METVFC'' (mitomycin C + cyclophosphamide + toyomycin + vincristine + 5-FU + cytosine arabinoside) and radiotherapy (5,000 rads in total) was given to 14 cases of limited disease of small cell carcinoma. Median survival was 8 months, one year and two year survival rates were 47% and 27%, respectively. Combined treatment with METVFC and small dose radiotherapy of 100 or 200 rads irradiation 4 hours before chemotherapy, followed by remission consolidation of 3,000 -- 4,000 rads radiotherapy, thereafter second line chemotherapy of ''COAM'' (cyclophosphamide + vincristine + ACNU + methotrexate) was given to 4 cases of limited disease of small cell carcinoma. All cases survived more than 1.5 years and two of them have retained complete remission more than 1.5 years. There are 6 cases with small cell carcinoma survived more than 3 years out of total 128 cases. They are all those of limited disease. They received combined treatment of chemotherapy and radiotherapy simultaneously or alternatively, followed by remission maintenance chemotherapy. One case of them died from cancer. Two cases died from another disease without lung cancer. Three cases survived healthy more than 3 to 8 years. In the limited disease, small cell carcinoma of the lung might be curable if the complete remission could continue more than three years. (author)

  14. Comparison of primary thyroid lymphoma with anaplastic thyroid carcinoma on computed tomographic imaging

    Energy Technology Data Exchange (ETDEWEB)

    Ishikawa, Hitoshi; Mitsuhashi, Norio; Niibe, Hideo [Gunma Univ., Maebashi (Japan). School of Medicine; Tamaki, Yoshio; Takahashi, Mitsuhiro; Higuchi, Keiko; Sakaino, Kouji; Nonaka, Tetsuo; Shioya, Mariko [Gunma Cancer Center, Ota (Japan)

    2002-02-01

    Primary non-Hodgkin's lymphoma (LY) and anaplastic carcinoma (AC) of the thyroid gland are rare malignant tumors, and the initial symptoms of these diseases are very similar. The aim of our study was to compare the characteristics of the two diseases using computed tomographic (CT) scans in order to make an accurate differential diagnosis. Ten patients with LY and 10 with AC were analyzed. Differences in the CT findings of the two diseases were evaluated before treatment and statistically tested with either Student's t-test or the chi-square test. In the analysis of characteristics of CT imaging, the existence of calcification and necrosis, and heterogeneous tumor were dominant findings in AC, and there was a statistically significant difference in frequency between the two diseases (p<0.01). Calcification detected in AC was usually multiple and/or gross (mean size: {phi}8.2 mm). All lymphadenopathies were delineated as having the same homogeneous attenuation as the tumors in the thyroid gland in LY, but were shown as irregular rim enhancement in AC. The CT features of the two diseases are characteristic in terms of calcification, necrosis, and tumor composition. Evaluation by means of CT imaging is useful in distinguishing between LY and AC. (author)

  15. Current Status of Targeted Therapy for Anaplastic Lymphoma Kinase in Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Li MA

    2014-12-01

    Full Text Available The rate of the anaplastic lymphoma kinase (ALK gene rearrangements in non-small cell lung cancer (NSCLC tissues is 3%-5%. The first-in-class ALK tyrosine kinase inhibitor, crizotinib, can effectively target these tumors represent a significant advance in the evolution of personalized medicine for NSCLC. A randomized phase III clinical trial in which superiority of crizotinib over chemotherapy was seen in previously treated ALK-positive NSCLC patients demonstrated durable responses and well tolerance in the majority of ALK-positive NSCLC patients treated with crizotinib. However, despite the initial responses, most patients develop acquired resistance to crizotinib. Several novel therapeutic approaches targeting ALK-positive NSCLC are currently under evaluation in clinical trials, including second-generation ALK inhibitors, such as LDK378, CH5424802 (RO5424802, and AP26113, and new agents shock protein 90 inhibitors. This review aims to present the current knowledge on this fusion gene, the treatment advances, and novel drug clinical trials in ALK rearranged NSCLC.

  16. Identifying the association between contrast enhancement pattern, surgical resection, and prognosis in anaplastic glioma patients

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yinyan; Jiang, Tao [Capital Medical University, Department of Neurosurgery, Beijing Tiantan Hospital, Beijing (China); Capital Medical University, Beijing Neurosurgical Institute, Beijing (China); Wang, Kai; Li, Shaowu; Ma, Jun [Capital Medical University, Department of Neuroradiology, Beijing Tiantan Hospital, Beijing (China); Wang, Jiangfei [Capital Medical University, Department of Neurosurgery, Beijing Tiantan Hospital, Beijing (China); Dai, Jianping [Capital Medical University, Beijing Neurosurgical Institute, Beijing (China); Capital Medical University, Department of Neuroradiology, Beijing Tiantan Hospital, Beijing (China)

    2016-04-15

    Contrast enhancement observable on magnetic resonance (MR) images reflects the destructive features of malignant gliomas. This study aimed to investigate the relationship between radiologic patterns of tumor enhancement, extent of resection, and prognosis in patients with anaplastic gliomas (AGs). Clinical data from 268 patients with histologically confirmed AGs were retrospectively analyzed. Contrast enhancement patterns were classified based on preoperative T1-contrast MR images. Univariate and multivariate analyses were performed to evaluate the prognostic value of MR enhancement patterns on progression-free survival (PFS) and overall survival (OS). The pattern of tumor contrast enhancement was associated with the extent of surgical resection in AGs. A gross total resection was more likely to be achieved for AGs with focal enhancement than those with diffuse (p = 0.001) or ring-like (p = 0.024) enhancement. Additionally, patients with focal-enhanced AGs had a significantly longer PFS and OS than those with diffuse (log-rank, p = 0.025 and p = 0.031, respectively) or ring-like (log-rank, p = 0.008 and p = 0.011, respectively) enhanced AGs. Furthermore, multivariate analysis identified the pattern of tumor enhancement as a significant predictor of PFS (p = 0.016, hazard ratio [HR] = 1.485) and OS (p = 0.030, HR = 1.446). Our results suggested that the contrast enhancement pattern on preoperative MR images was associated with the extent of resection and predictive of survival outcomes in AG patients. (orig.)

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

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    Arai Hajime

    2007-08-01

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

  18. Anaplastic carcinoma of the pancreas: Is there a role for palliative surgical procedure?

    Directory of Open Access Journals (Sweden)

    Rajan Vaithianathan

    2014-01-01

    Full Text Available Anaplastic carcinoma (AC or undifferentiated carcinoma of the pancreas is a rare variant among the malignant pancreatic neoplasms. These tumors have a poor prognosis with survival measured in months. The role of surgical palliation to improve the quality of life is not well defined in these patients. We report a case of AC of pancreas in a 65-year-old male patient. Patient had upper abdominal pain with frequent bilious vomiting. Computed tomography scan of the abdomen showed a mass in the body of pancreas with possible infiltration of duodenojejunal flexure (DJF. Laparotomy revealed an inoperable mass with posterior fixity and involvement of the DJF. Patient underwent a palliative duodenojejunostomy. Tissue biopsy from the tumor showed pleomorphic type AC with giant cells. Patient had good symptomatic relief from profuse vomiting and progressed well at follow up. AC of pancreas is a rare and aggressive malignancy with dismal outlook. If obstructive symptoms are present due to duodenal involvement, a palliative bypass may be a worthwhile surgical option in selected cases.

  19. A bone metastases model of anaplastic thyroid carcinoma in athymic nude mice

    International Nuclear Information System (INIS)

    Anaplastic thyroid carcinoma (ATC), an aggressive form of thyroid cancer, represents less than 2% of all thyroid cancers. The survival of patients with ATC remains low especially when accompanied with bone metastasis. This study aims to establish a reproducible animal model of bone metastasis of ATC which may be useful for further research on novel treatment strategy. Eight 6-8 week old female athymic nude mice were randomly selected. ATC cell line ARO cells were injected into the left ventricular cavity of each mouse respectively. Each mouse was imaged using a dedicated small-animal PET/CT scanner after successful injection of [18F]-FDG under deep anesthesia. Pathological examination was carried out to confirm the bone metastases of ATC. Histopathology established ATC bone metastases in five nude mice’s tibia. Similarly, PET image displayed significantly increased radioactivity (P<0.01) in the established bone metastasis compared with the control normal tibia. Both micro-PET/CT and histomorphometric measurement confirmed the bone metastases model of ATC in nude mice by left ventricular cavity injection of ARO cell line. The bone metastases model of ATC will thus facilitate the understanding of its pathogenesis and aid in the development of novel therapies.

  20. Anaplastic carcinoma associated with a mucinous cystic neoplasm of the pancreas during pregnancy: Report of a case and a review of the literature

    Institute of Scientific and Technical Information of China (English)

    Kenichi Hakamada; Takuya Miura; Akitoshi Kimura; Masaki Nara; Yoshikazu Toyoki; Shunij Narumi; Mutsuo Sasak

    2008-01-01

    Oncogenesis of anaplastic carcinoma of the pancreas is a subject of controversy, because it shows sarcomatous nature with extremely poor prognosis. We herein report an unusual case of anaplastic carcinoma occurring with a recurrent mucinous cystic neoplasm in a 38-year-old female. A 10-cm retroperitoneal cystic mass was pointed out in the first pregnancy and a probable diagnosis of mucinous cystic neoplasm was made in October 2000. She refused surgery first and delivered her baby uneventfully. During her second pregnancy in 2002, however, she presented hematemesis and underwent urgent distal pancreatectomy, splenectomy and partial resection of the gastric wall where the tumor perforated. A diagnosis of borderline-type mucinous cystic neoplasm with ovarian-like stroma was made. Nine months later, CT visualized a recurrent cystic tumor near the pancreatic stump, which was subsequently resected. Pathology revealed that the tumor was composed of two different components of borderline-type mucinous cystic neoplasm and anaplastic carcinoma. The latter was intensely positive for vimentin, CD68, p53 and focally for cytokeratin, suggesting both sarcomatous and carcinomatous differentiation. She survived four years after the second surgery without tumor recurrence. Although the origin of anaplastic carcinoma has not been determined yet, it should be remembered that anaplastic carcinoma can occur in association with mucinous cystic neoplasm of more benign histology.

  1. {sup 18}F-fluorodeoxyglucose positron emission tomography and computed tomography in anaplastic thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Poisson, Thomas [Institut Gustave Roussy and University Paris-Sud XI, Department of Nuclear Medicine and Endocrine Oncology, Villejuif Cedex (France); Service de Medecine Nucleaire, Hopital Bichat, Paris (France); Deandreis, Desiree; Leboulleux, Sophie; Lumbroso, Jean; Baudin, Eric [Institut Gustave Roussy and University Paris-Sud XI, Department of Nuclear Medicine and Endocrine Oncology, Villejuif Cedex (France); Bidault, Francois [Institut Gustave Roussy and University Paris-Sud XI, Department of Radiology, Villejuif Cedex (France); Bonniaud, Guillaume [Institut Gustave Roussy and University Paris-Sud XI, Department of Medical Physics, Villejuif Cedex (France); Baillot, Sylvain; Auperin, Anne [Institut Gustave Roussy and University Paris-Sud XI, Department of Epidemiology, Villejuif Cedex (France); Ghuzlan, Abir Al [Institut Gustave Roussy and University Paris-Sud XI, Department of Pathology, Villejuif Cedex (France); Travagli, Jean-Paul [Institut Gustave Roussy and University Paris-Sud XI, Department of Endocrine Surgery, Villejuif Cedex (France); Schlumberger, Martin [Institut Gustave Roussy and University Paris-Sud XI, Department of Nuclear Medicine and Endocrine Oncology, Villejuif Cedex (France); Institut Gustave Roussy, Service de Medecine Nucleaire et de Cancerologie Endocrinienne, Villejuif (France)

    2010-12-15

    Our aim was to evaluate in anaplastic thyroid carcinoma (ATC) patients the value of {sup 18}F-FDG PET/CT compared with total body computed tomography (CT) using intravenous contrast material for initial staging, prognostic assessment, therapeutic monitoring and follow-up. Twenty consecutive ATC patients underwent PET/CT for initial staging. PET/CT was performed again during follow-up. The gold standard was progression on imaging follow-up (CT or PET/CT) or confirmation with another imaging modality. A total of 265 lesions in 63 organs were depicted in 18 patients. Thirty-five per cent of involved organs were demonstrated only with PET/CT and one involved organ only with CT. In three patients, the extent of disease was significantly changed with PET/CT that demonstrated unknown metastases. Initial treatment modalities were modified by PET/CT findings in 25% of cases. The volume of FDG uptake ({>=}300 ml) and the intensity of FDG uptake (SUV{sub max} {>=}18) were significant prognostic factors for survival. PET/CT permitted an earlier assessment of tumour response to treatment than CT in 4 of the 11 patients in whom both examinations were performed. After treatment with combined radiotherapy and chemotherapy, only the two patients with a negative control PET/CT had a confirmed complete remission at 14 and 38 months; all eight patients who had persistent FDG uptake during treatment had a clinical recurrence and died. FDG PET/CT appears to be the reference imaging modality for ATC at initial staging and seems promising in the early evaluation of treatment response and follow-up. (orig.)

  2. 18F-fluorodeoxyglucose positron emission tomography and computed tomography in anaplastic thyroid cancer

    International Nuclear Information System (INIS)

    Our aim was to evaluate in anaplastic thyroid carcinoma (ATC) patients the value of 18F-FDG PET/CT compared with total body computed tomography (CT) using intravenous contrast material for initial staging, prognostic assessment, therapeutic monitoring and follow-up. Twenty consecutive ATC patients underwent PET/CT for initial staging. PET/CT was performed again during follow-up. The gold standard was progression on imaging follow-up (CT or PET/CT) or confirmation with another imaging modality. A total of 265 lesions in 63 organs were depicted in 18 patients. Thirty-five per cent of involved organs were demonstrated only with PET/CT and one involved organ only with CT. In three patients, the extent of disease was significantly changed with PET/CT that demonstrated unknown metastases. Initial treatment modalities were modified by PET/CT findings in 25% of cases. The volume of FDG uptake (≥300 ml) and the intensity of FDG uptake (SUVmax ≥18) were significant prognostic factors for survival. PET/CT permitted an earlier assessment of tumour response to treatment than CT in 4 of the 11 patients in whom both examinations were performed. After treatment with combined radiotherapy and chemotherapy, only the two patients with a negative control PET/CT had a confirmed complete remission at 14 and 38 months; all eight patients who had persistent FDG uptake during treatment had a clinical recurrence and died. FDG PET/CT appears to be the reference imaging modality for ATC at initial staging and seems promising in the early evaluation of treatment response and follow-up. (orig.)

  3. Tumor-associated macrophages (TAMs form an interconnected cellular supportive network in anaplastic thyroid carcinoma.

    Directory of Open Access Journals (Sweden)

    Bernard Caillou

    Full Text Available BACKGROUND: A relationship between the increased density of tumor-associated macrophages (TAMs and decreased survival was recently reported in thyroid cancer patients. Among these tumors, anaplastic thyroid cancer (ATC is one of the most aggressive solid tumors in humans. TAMs (type M2 have been recognized as promoting tumor growth. The purpose of our study was to analyze with immunohistochemistry the presence of TAMs in a series of 27 ATC. METHODOLOGY/PRINCIPAL FINDINGS: Several macrophages markers such as NADPH oxidase complex NOX2-p22phox, CD163 and CD 68 were used. Immunostainings showed that TAMs represent more than 50% of nucleated cells in all ATCs. Moreover, these markers allowed the identification of elongated thin ramified cytoplasmic extensions, bestowing a "microglia-like" appearance on these cells which we termed "Ramified TAMs" (RTAMs. In contrast, cancer cells were totally negative. Cellular stroma was highly simplified since apart from cancer cells and blood vessels, RTAMs were the only other cellular component. RTAMs were evenly distributed and intermingled with cancer cells, and were in direct contact with other RTAMs via their ramifications. Moreover, RTAMs displayed strong immunostaining for connexin Cx43. Long chains of interconnected RTAMs arose from perivascular clusters and were dispersed within the tumor parenchyma. When expressed, the glucose transporter Glut1 was found in RTAMs and blood vessels, but rarely in cancer cells. CONCLUSION: ATCs display a very dense network of interconnected RTAMs in direct contact with intermingled cancer cells. To our knowledge this is the first time that such a network is described in a malignant tumor. This network was found in all our studied cases and appeared specific to ATC, since it was not found in differentiated thyroid cancers specimens. Taken together, these results suggest that RTAMs network is directly related to the aggressiveness of the disease via metabolic and trophic

  4. Dosimetric comparison between helical tomotherapy and volumetric modulated arc-therapy for non-anaplastic thyroid cancer treatment

    International Nuclear Information System (INIS)

    To evaluate and compare dosimetric parameters of volumetric modulated arctherapy (VMAT) and helical tomotherapy (HT) for non-anaplastic thyroid cancer adjuvant radiotherapy. Twelve patients with non-anaplastic thyroid cancer at high risk of local relapse received adjuvant external beam radiotherapy with curative intent in our institution, using a two-dose level prescription with a simultaneous integrated boost approach. Each patient was re-planned by the same physicist twice using both VMAT and HT. Several dosimetric quality indexes were used: target coverage index (proportion of the target volume covered by the reference isodose), healthy tissue conformity index (proportion of the reference isodose volume including the target volume), conformation number (combining both previous indexes), Dice Similarity Coefficient (DSC), and homogeneity index ((D2%-D98%)/prescribed dose). Dose-volume histogram statistics were also compared. HT provided statistically better target coverage index and homogeneity index for low risk PTV in comparison with VMAT (respectively 0.99 vs. 0.97 (p = 0.008) and 0.22 vs. 0.25 (p = 0.016)). However, HT provided poorer results for healthy tissue conformity index, conformation number and DSC with low risk and high risk PTV. As regards organs at risk sparing, by comparison with VMAT, HT statistically decreased the D2% to medullary canal (25.3 Gy vs. 32.6 Gy (p = 0.003)). Besides, HT allowed a slight sparing dose for the controlateral parotid (Dmean: 4.3 Gy vs. 6.6 Gy (p = 0.032)) and for the controlateral sub-maxillary gland (Dmean: 29.1 Gy vs. 33.1 Gy (p = 0.041)). Both VMAT and HT techniques for adjuvant treatment of non-anaplastic thyroid cancer provide globally attractive treatment plans with slight dosimetric differences. However, helical tomotherapy clearly provides a benefit in term of medullary canal sparing

  5. Primary anaplastic astrocytoma of the brain after prophylactic cranial irradiation in a case of acute lymphoblastic leukemia: Case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Imtiaz Ahmed

    2014-01-01

    Full Text Available A 6½-year-old boy had developed acute lymphoblastic leukemia and was treated with systemic chemotherapy, intrathecal triple drug regimen and prophylactic cranial irradiation. After 10 years he developed anaplastic astrocytoma of the postero-superior cerebellum on the left side while leukemia was in remission. He was treated with surgical excision, followed by adjuvant three dimensional conformal radiotherapy and is on salvage chemotherapy with temozolamide. It is possible that the anaplastic astrocytoma may be a radiation induced malignancy.

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

    Science.gov (United States)

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

    2015-02-01

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

  7. Non-anaplastic peripheral T cell lymphoma in children and adolescents-an international review of 143 cases.

    Science.gov (United States)

    Mellgren, K; Attarbaschi, A; Abla, O; Alexander, S; Bomken, S; Bubanska, E; Chiang, A; Csóka, M; Fedorova, A; Kabickova, E; Kapuscinska-Kemblowska, L; Kobayashi, R; Krenova, Z; Meyer-Wentrup, F; Miakova, N; Pillon, M; Plat, G; Uyttebroeck, A; Williams, D; Wróbel, G; Kontny, U

    2016-08-01

    Peripheral T cell lymphomas (PTCL) are rare in children and adolescents, and data about outcome and treatment results are scarce. The present study is a joint, international, retrospective analysis of 143 reported cases of non-anaplastic PTCL in patients event-free survival was (pEFS) 0.45 ± 0.05. Patients with SP TCL had a good outcome with 5-year pOS of 0.78 ± 0.1 while patients with HS TCL were reported with 5-year pOS of only 0.13 ± 0.12. Twenty-five percent of the patients were reported to have a pre-existing condition, and this group had a dismal outcome with 5-year pOS of 0.29 ± 0.09. The distribution of non-anaplastic PTCL subtypes in pediatric and adolescent patients differs from what is reported in adult patients. Overall outcome depends on the subtype with some doing better than others. Pre-existing conditions are frequent and associated with poor outcomes. There is a clear need for subtype-based treatment recommendations for children and adolescents with PTCL. PMID:27270301

  8. A North American brain tumor consortium phase II study of poly-ICLC for adult patients with recurrent anaplastic gliomas.

    Science.gov (United States)

    Butowski, Nicholas; Lamborn, Kathleen R; Lee, Bee L; Prados, Michael D; Cloughesy, Timothy; DeAngelis, Lisa M; Abrey, Lauren; Fink, Karen; Lieberman, Frank; Mehta, Minesh; Ian Robins, H; Junck, Larry; Salazar, Andres M; Chang, Susan M

    2009-01-01

    This phase II study was designed to determine the objective response rate and 6-month progression free survival of adult patients with recurrent supratentorial anaplastic glioma when treated with the immune modulator, polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose (poly-ICLC). This was an open-labeled, single arm phase II study. Patients were treated with poly-ICLC alone. Patients may have had treatment for no more than two prior relapses. Treatment with poly-ICLC continued until tumor progression. Fifty five patients were enrolled in the study. Ten were ineligible after central review of pathology. Eleven percent of patients (5 of 45) had a radiographic response. Time to progression was known for 39 patients and 6 remain on treatment. The estimated 6-month progression free survival was 24%. The median survival time was 43 weeks. Poly-ICLC was well tolerated, but there was no improvement in 6-month progression free survival compared to historical database nor was there an encouraging objective radiographic response rate. Based on this study, poly-ICLC does not improve 6moPFS in patients with recurrent anaplastic gliomas but may be worth further study in combination with agents such as temozolomide. PMID:18850068

  9. MGMT-STP27 Methylation Status as Predictive Marker for Response to PCV in Anaplastic Oligodendrogliomas and Oligoastrocytomas. A Report from EORTC Study 26951

    NARCIS (Netherlands)

    van den Bent, Martin J.; Erdem-Eraslan, Lale; Idbaih, Ahmed; de Rooi, Johan; Eilers, Paul H. C.; Spliet, Wim G. M.; den Dunnen, Wilfred F. A.; Tijssen, Cees; Wesseling, Pieter; Smitt, Peter A. E. Sillevis; Kros, Johan M.; Gorlia, Thierry; French, Pim J.

    2013-01-01

    Purpose: The long-term follow-up results from the EORTC-26951 trial showed that the addition of procarbazine, CCNU, and vincristine (PCV) after radiotherapy increases survival in anaplastic oligodendrogliomas/oligoastrocytomas (AOD/AOA). However, some patients appeared to benefit more from PCV treat

  10. MGMT-STP27 methylation status as predictive marker for response to PCV in anaplastic Oligodendrogliomas and Oligoastrocytomas. A report from EORTC study 26951

    NARCIS (Netherlands)

    Bent, M.J. van den; Erdem-Eraslan, L.; Idbaih, A.; Rooi, J. de; Eilers, P.H.; Spliet, W.G.; Dunnen, W.F. den; Tijssen, C.; Wesseling, P.; Smitt, P.A.; Kros, J.M.; Gorlia, T.; French, P.J.

    2013-01-01

    PURPOSE: The long-term follow-up results from the EORTC-26951 trial showed that the addition of procarbazine, CCNU, and vincristine (PCV) after radiotherapy increases survival in anaplastic oligodendrogliomas/oligoastrocytomas (AOD/AOA). However, some patients appeared to benefit more from PCV treat

  11. Impact of hydrolysis-mediated clearance on the pharmacokinetics of novel anaplastic lymphoma kinase inhibitors.

    Science.gov (United States)

    Teffera, Yohannes; Berry, Loren M; Brake, Rachael L; Lewis, Richard T; Saffran, Douglas C; Moore, Earl; Liu, Jingzhou; Zhao, Zhiyang

    2013-01-01

    Compound 1 [(E)-4-fluoro-N-(6-((4-(2-hydroxypropan-2-yl)piperidin-1-yl)methyl)-1-((1S,4S)-4-(isopropylcarbamoyl)cyclohexyl)-1H-benzo[d]imidazol-2(3H)-ylidene)benzamide], a new, potent, selective anaplastic lymphoma kinase (ALK) inhibitor with potential application for the treatment of cancer, was selected as candidate to advance into efficacy studies in mice. However, the compound underwent mouse-specific enzymatic hydrolysis in plasma to a primary amine product (M1). Subsequent i.v. pharmacokinetics studies in mice showed that compound 1 had high clearance (CL) and a short half-life. Oral dose escalation studies in mice indicated that elimination of compound 1 was saturable, with higher doses achieving sufficient exposures above in vitro IC(50). Chemistry efforts to minimize hydrolysis resulted in the discovery of several analogs that were stable in mouse plasma. Three were taken in vivo into mice and showed decreased CL corresponding to increased in vitro stability in plasma. However, the more stable compounds also showed reduced potency against ALK. Kinetic studies in NADPH-fortified and unfortified microsomes and plasma produced submicromolar K(m) values and could help explain the saturation of elimination observed in vivo. Predictions of CL based on kinetics from hydrolysis and NADPH-dependent pathways produced predicted hepatic CL values of 3.8, 3.0, 1.6, and 1.2 l/h⋅kg for compound 1, compound 2 [(E)-3,5-difluoro-N-(6-((4-(2-hydroxypropan-2-yl)piperidin-1-yl)methyl)-1-((1s,4s)-4-(isopropylcarbamoyl)cyclohexyl)-1H-benzo[d]imidazol-2(3H)-ylidene)benzamide], compound 3 [(E)-3-chloro-5-fluoro-N-(6-((4-(2-hydroxypropan-2-yl)piperidin-1-yl)methyl)-1-((1s,4s)-4-(isopropylcarbamoyl)cyclohexyl)-1H-benzo[d]imidazol-2(3H)-ylidene)benzamide], and compound 4 [(E)-N-(6-((4-(2-hydroxypropan-2-yl)piperidin-1-yl)methyl)-1-((1s,4s)-4-(isopropylcarbamoyl)cyclohexyl)-1H-benzo[d]imidazol-2(3H)-ylidene)-3-(trifluoromethyl)benzamide], respectively. The in vivo observed CLs for

  12. Successful palliative approach with high-intensity focused ultrasound in a patient with metastatic anaplastic pancreatic carcinoma: a case report

    Science.gov (United States)

    Ungaro, Antonio; Orsi, Franco; Casadio, Chiara; Galdy, Salvatore; Spada, Francesca; Cella, Chiara Alessandra; Tonno, Clementina Di; Bonomo, Guido; Vigna, Paolo Della; Murgioni, Sabina; Frezza, Anna Maria; Fazio, Nicola

    2016-01-01

    We report a case of a 74-year-old man with a metastatic anaplastic pancreatic carcinoma (APC). After an early tumour progression on first-line chemotherapy with cisplatin and gemcitabine, even though it was badly tolerated, he was treated with a combination of systemic modified FOLFIRI and high-intensity focused ultrasound (HIFU) on the pancreatic mass. A tumour showing partial response with a clinical benefit was obtained. HIFU was preferred to radiotherapy because of its shorter course and minimal side effects, in order to improve the patient’s clinical conditions. The patient is currently on chemotherapy, asymptomatic with a good performance status. In referral centres, with specific expertise, HIFU could be safely and successfully combined with systemic chemotherapy for treatment of metastatic pancreatic carcinoma. PMID:27170835

  13. Successful palliative approach with high-intensity focused ultrasound in a patient with metastatic anaplastic pancreatic carcinoma: a case report.

    Science.gov (United States)

    Ungaro, Antonio; Orsi, Franco; Casadio, Chiara; Galdy, Salvatore; Spada, Francesca; Cella, Chiara Alessandra; Tonno, Clementina Di; Bonomo, Guido; Vigna, Paolo Della; Murgioni, Sabina; Frezza, Anna Maria; Fazio, Nicola

    2016-01-01

    We report a case of a 74-year-old man with a metastatic anaplastic pancreatic carcinoma (APC). After an early tumour progression on first-line chemotherapy with cisplatin and gemcitabine, even though it was badly tolerated, he was treated with a combination of systemic modified FOLFIRI and high-intensity focused ultrasound (HIFU) on the pancreatic mass. A tumour showing partial response with a clinical benefit was obtained. HIFU was preferred to radiotherapy because of its shorter course and minimal side effects, in order to improve the patient's clinical conditions. The patient is currently on chemotherapy, asymptomatic with a good performance status. In referral centres, with specific expertise, HIFU could be safely and successfully combined with systemic chemotherapy for treatment of metastatic pancreatic carcinoma. PMID:27170835

  14. Alectinib-Induced Alopecia in a Patient with Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer

    Science.gov (United States)

    Koizumi, Tomonobu; Fukushima, Toshirou; Gomi, Daisuke; Kobayashi, Takashi; Sekiguchi, Nodoka; Sakamoto, Akiyuki; Sasaki, Shigeru; Mamiya, Keiko

    2016-01-01

    Alectinib, a novel alternative anaplastic lymphoma kinase (ALK) inhibitor, is highly effective against ALK-positive non-small cell lung cancer (NSCLC) and is well tolerated. Molecular targeted agents generally have little contribution to alopecia. We encountered a case of alopecia that developed gradually over 2 months after initiation of alectinib administration for the treatment of ALK-positive NSCLC. The patient had no history of alopecia in previous treatments of cisplatin + pemetrexed and crizotinib. The present case indicates that alopecia should be taken into consideration as toxicity during alectinib treatment, which could adversely affect the psychological and emotional condition and quality of life even in patients treated with specific molecular targeted agents. PMID:27194980

  15. Differentiation between recurrent tumor and radiation necrosis in a child with anaplastic ependymoma after chemotherapy and radiation therapy

    International Nuclear Information System (INIS)

    Background: In patients after treatment for malignant brain tumors, a clear distinction between tumor recurrence and radiation necrosis can be challenging. This case report describes the diagnostic workup in a child with anaplastic ependymoma and inconclusive MRI (magnetic resonance imaging) and PET (positron emission tomography) findings. Case Report: 1.5 years after resection, hyperfractionated radiotherapy and chemotherapy of an anaplastic ependymoma in the right parietal region, the cranial MRI of an 11-year-old girl showed multiple small contrast-enhanced lesions in the frontal cortex. In the following months, these lesions increased in number and size and neurologic symptoms developed. Diagnostic workup included repeated MRI scans, PET with an 18F-amino acid and 18F-fluorodeoxyglucose (FDG), as well as a brain biopsy. Results: Amino acid PET, performed when the lesions were still small, showed multiple small areas of mild uptake in close correlation to the MRI lesions. Although not typical, this result was suspicious of tumor seeding, the more since the lesions appeared in gray matter areas outside the high-dose-rate irradiation field. A biopsy, performed 6 months later when the clinical appearance worsened, showed no tumor tissue. FDG PET, performed after the size and number of the lesions had increased, showed no intensely increased glucose metabolism, a high-grade recurrent tumor was therefore very unlikely. In the following months, the clinical picture stabilized. Conclusion: The final interpretation of the lesions was multiple focal radiation necrosis based on perfusion abnormalities after chemotherapy and conformal hyperfractionated radiotherapy, probably due to an individually enhanced vulnerability of the cerebral vessels. (orig.)

  16. 131I therapy for hyperthyroidism and consequent appearing of anaplastic carcinoma of the thyroid: simple case-report or real pathophysiologic link?

    Directory of Open Access Journals (Sweden)

    G. Scanelli

    2013-05-01

    Full Text Available BACKGROUND 131I is usually employed for the therapy of hyperfunctioning thyroid diseases. This β-emitting radioisotope acts releasing its radiations in small tissue volumes, but it is mandatory to consider, also for the small doses, the carcinogenic risk, well documented with the high 131I dosages used to cure differentiated thyroid cancers. METHODS We describe a case of anaplastic thyroid carcinoma appeared 4 years after therapy with 131I for Graves’ disease. The patient was treated both surgically and with thyonamides for Graves’ disease 20 years before; thereafter she underwent simple nephrectomy owing to Grawitz disease. After some years of well being, she was treated with 131I for a relapse of Graves’ disease. Four years later, she was treated with interleukin-2 and TNF-α, owing to distant metastases (pancreas, liver and lung of Grawitz cancer. Some months later, because of a rapid enlargement of the thyroid gland, she was thyroidectomized and anaplastic thyroid cancer was histologically documented. DISCUSSION AND CONCLUSIONS It is very difficult to investigate the possible transformation of a benign thyroid lesion to a malignant one, and data from the literature are conflicting. Fractioned doses of 131I are known to induce less cancers than high doses: they allow DNA to repair. Nevertheless, in patients with altered or non valid genetic repair’s mechanisms (i.e. patients with p53 mutations and, for this reason, prone to develop cancers, even low doses of 131I can induce carcinogenetic effects. In a patient with a history of cancer, who subsequently develops hyperthyroidism, even low doses of 131I can induce anaplastic thyroid cancer; in these subjects, therefore, other treatments than 131I could be preferred for the therapy of Graves’ disease. In our peculiar case, moreover, some studies have noteworthy demonstrated that certain cytokines (IL-1, TGF-β1 e TNF-α can, rather than inhibit, induce anaplastic thyroid cancer cells

  17. Role of radiotherapy in anaplastic ependymoma in children under age of 3 years: Results of the prospective German brain tumor trials HIT-SKK 87 and 92

    International Nuclear Information System (INIS)

    Background and purpose: To evaluate the outcome of very young children with anaplastic ependymoma after delayed or omitted radiotherapy (RT). Materials and methods: Children under age of 3 years with anaplastic ependymoma were enrolled in the HIT-SKK 87 trial from 1987. After surgery, low-risk patients (R0, M0) received maintenance chemotherapy until elective RT at age of three. In high-risk patients (R+, M+) intensive induction chemotherapy was followed by maintenance chemotherapy and subsequently delayed RT. If there was, progression radiotherapy started immediately. In the HIT-SKK 92, trial MTX-based chemotherapy was applied. RT was administered in non-responders only. Results: Thirty-four children with anaplastic ependymoma were eligible (age 1.0-33.0 months). All children received chemotherapy. In 13 children, no RT was administered. Preventive RT after chemotherapy was given in nine, and salvage RT in 12 children. OS and PFS rates after 3-year were 55.9 and 27.3%, respectively. Twenty-five children relapsed. Positive impact on survival was observed in children with higher age, M0-stage, complete resection, and treatment with radiotherapy. Without RT only 3/13, children survived. Conclusion: Delaying RT jeopardizes survival even after intensive chemotherapy. Predominant site of failure is the primary tumor site. RT of the neuraxis should be omitted in localized disease

  18. Crizotinib as a personalized alternative for targeted anaplastic lymphoma kinase rearrangement in previously treated patients with non-small-cell lung cancer

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    Guo L

    2015-10-01

    Full Text Available Liting Guo,1,* Haijun Zhang,1,* Weiwei Shao,2 Baoan Chen1 1Department of Hematology and Oncology (Key Department of Jiangsu Medicine, The Affiliated Zhongda Hospital, Medical School of Southeast University, Nanjing, 2Department of Pathology, the First People’s Hospital of Yancheng, Yancheng, Jiangsu, People’s Republic of China *These authors contributed equally to this work Abstract: Crizotinib, the first clinically designed and synthesized as a tyrosine kinase inhibitor targeting mesenchymal–epithelial transition factor, indicating marked anticancer activity in patients with advanced, anaplastic lymphoma kinase-positive non-small-cell lung cancer, was approved by the US Food and Drug Administration in 2011. In this review, we focus on the efficacy of crizotinib compared with chemotherapy in advanced anaplastic lymphoma kinase-positive lung cancer and present the role of crizotinib as a personalized alternative in previously treated patients with non-small-cell lung cancer. Keywords: crizotinib, anaplastic lymphoma kinase rearrangement, non-small-cell lung cancer 

  19. Radiation therapy and bromodeoxyuridine chemotherapy followed by procarbazine, lomustine, and vincristine for the treatment of anaplastic gliomas

    International Nuclear Information System (INIS)

    Purpose: To conduct a Phase II study to evaluate the long-term efficacy and safety of radiotherapy combined with intravenous bromodeoxyuridine for patients with anaplastic glioma tumors. Methods and Materials: Between 1983 and 1987, study patients received 1.7-1.8 Gy radiation once a day, Monday through Friday, to a total dose of 60 Gy. On the Thursday prior to beginning radiotherapy and for the next 5 weeks (6 weeks total), patients received a continuous 96 h intravenous infusion of bromodeoxyuridine at 0.8 g/m2/24 h; following radiotherapy, patients received procarbazine, lomustine (CCNU), and vincristine (PCV) for 1 year or until tumor progressed. Results: One-hundred thirty eight patients (median age, 43 years) were evaluable for analysis. Estimated 4-year survival for the anaplastic astrocytoma (AA) stratum (n 116) is 46%. For the astrocytoma (ASTRO) stratum (n = 22), the 6-year survival is estimated at 79%. Estimated 4-year progression-free survival for AAs is 42%, and for ASTROs, 68%. Whole brain irradiation was used in 23% and limited-field irradiation in 77%; patients receiving limited-field irradiation had a better survival rate (p = 0.07). Total tumor resection was performed in 15%, partial resection in 53%, and biopsy only in 32%. For the 81 patients with tumor recurrence, 34 (42%) are known to have received additional treatment(s). For AA, fits of the Cox proportional hazards regression model showed that covariates individually predictive of survival were younger age (p < 0.001), Karnofsky performance score (p = 0.04), and extent of surgery (p = 0.04); limited-field irradiation was not significant (p = 0.10). Major toxicities were rash during Weeks 1 through 6 requiring dose modification in 14%, Grade ≥III leukopenia in 18%, and Grade ≥III thrombocytopeni in 9%. Conclusion: The study suggests that the bromodeoxyuridine-radiotherapy-PCV, compared with other published therapies, can improve progression-free survival, and aggressive treatment of ASTRO

  20. The effect of 17-allylamino-17-demethoxygeldanamycin alone or in combination with paclitaxel on anaplastic thyroid carcinoma cells.

    Science.gov (United States)

    Kim, Si Hyoung; Kang, Jun Goo; Kim, Chul Sik; Ihm, Sung-Hee; Choi, Moon Gi; Yoo, Hyung Joon; Lee, Seong Jin

    2015-04-01

    The effect of 17-allylamino-17-demethoxygeldanamycin (17-AAG), an hsp90 inhibitor, alone or in combination with paclitaxel on survival of anaplastic thyroid carcinoma (ATC) was evaluated. In 8505C and CAL62 cells, after treatment of 17-AAG, cell viability decreased, and the percentage of dead cells increased. 17-AAG did not cause cleavage of caspase-3 protein, and change expression of IAPs. Pretreatment of z-VAD-fmk did not alter cell viability and the percentage of dead cells. In 17-AAG-treated cells, knockdown of p53 rescued growth inhibition, while cycloheximide attenuated cell death. When cells were treated with both 17-AAG and paclitaxel, all of the combination index values were higher than 1, indicating antagonism between 17-AAG and paclitaxel. In 17-AAG- and paclitaxel-treated cells, compared with paclitaxel alone-treated cells, the protein levels of hsp90, hsp70, and hsc70 increased. In conclusion, our results suggest that 17-AAG induces non-apoptotic cell death requiring de novo protein synthesis in ATC cells. Moreover, these results demonstrate that 17-AAG antagonizes paclitaxel with concomitant alterations in hsp90 client proteins in ATC cells. PMID:25096912

  1. Development of anaplastic lymphoma kinase (ALK inhibitors and molecular diagnosis in ALK rearrangement-positive lung cancer

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    Iwama E

    2014-03-01

    Full Text Available Eiji Iwama,1,2 Isamu Okamoto,3 Taishi Harada,2 Koichi Takayama,2 Yoichi Nakanishi2,3 1Department of Comprehensive Clinical Oncology, Faculty of Medical Sciences, Kyushu University, 2Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, 3Center for Clinical and Translational Research, Kyushu University Hospital, Fukuoka, Japan Abstract: The fusion of echinoderm microtubule-associated protein-like 4 with anaplastic lymphoma kinase (ALK was identified as a transforming gene for lung cancer in 2007. This genetic rearrangement accounts for 2%–5% of non-small-cell lung cancer (NSCLC cases, occurring predominantly in younger individuals with adenocarcinoma who are never- or light smokers. A small-molecule tyrosine-kinase inhibitor of ALK, crizotinib, was rapidly approved by the US Food and Drug Administration on the basis of its pronounced clinical activity in patients with ALK rearrangement-positive NSCLC. Next-generation ALK inhibitors, such as alectinib, LDK378, and AP26113, are also being developed in ongoing clinical trials. In addition, the improvement and validation of methods for the detection of ALK rearrangement in NSCLC patients will be key to the optimal clinical use of ALK inhibitors. We here summarize recent progress in the development of new ALK inhibitors and in the molecular diagnosis of ALK rearrangement-positive NSCLC. Keywords: ALK, rearrangement, NSCLC, ALK inhibitor, targeted therapy, diagnosis

  2. IDH1 mutation and MGMT methylation status predict survival in patients with anaplastic astrocytoma treated with temozolomide-based chemoradiotherapy.

    Science.gov (United States)

    Minniti, Giuseppe; Scaringi, Claudia; Arcella, Antonella; Lanzetta, Gaetano; Di Stefano, Domenica; Scarpino, Stefania; Bozzao, Alessandro; Pace, Andrea; Villani, Veronica; Salvati, Maurizio; Esposito, Vincenzo; Giangaspero, Felice; Enrici, Riccardo Maurizi

    2014-06-01

    Several molecular markers have been proposed as predictors of outcome in patients with high grade gliomas. We report a retrospective multicenter study of 97 consecutive adult patients with anaplastic astrocytoma (AA) treated with radiation therapy (RT) plus concomitant and adjuvant temozolomide (TMZ) between October 2004 and March 2012. Correlations between the isocitrate dehydrogenase 1 (IDH1) mutation and O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation with survival outcomes have been analyzed. At a median follow-up time of 46 months (range 12-89 months), median and 5-year overall survival rates were 50.5 months (95 % CI, 37.8-63.2) and 38% (95 % CI, 25.7-50.7%), and median and 5-year progression-free survival rates were 36 months (95% CI, 28.5-44.0) and 22 % (95 % CI, 10-34%), respectively. IDH1 mutation and MGMT promoter methylation were present in 54 and 60% of evaluable patients, respectively. Multivariate Cox proportional hazards regression analysis showed that IDH1 mutation (P = 0.001), MGMT methylation (P = 0.01), age < 50 years (P = 0.02), and extent of resection (P = 0.04) were significantly associated with longer survival. Our study confirms the favorable prognostic value of IDH1 mutation and MGMT methylation in patients with AA treated with RT plus concomitant and adjuvant TMZ. The superiority of combined radiochemotherapy over other treatment modalities remains to be demonstrated. PMID:24748470

  3. 甲状腺间变癌的CT影像特点%CT imaging features of anaplastic thyroid carcinoma

    Institute of Scientific and Technical Information of China (English)

    史震山; 庄茜; 游瑞雄; 曹代荣; 李跃明

    2013-01-01

    目的 分析甲状腺间变癌的CT表现,评价CT在明确甲状腺间变癌诊断及鉴别诊断中的价值.方法 回顾性分析经手术、病理证实的10例甲状腺间变癌的临床及CT资料,女7例、男3例;发病年龄25~78岁,中位年龄为61岁;均采用MSCT行平扫及增强扫描.结果 10例中8例为单侧病灶,其中2例病灶较大侵及峡部;2例病灶累及双侧甲状腺.肿瘤最大径为2.9~12.8 cm,平均(4.5±1.4)cm;病灶边缘均不光整且有甲状腺被膜外侵征象;病灶平扫密度不均匀,病灶内均可见坏死区;病灶内伴钙化者7枚,钙化形态各异,以单发粗颗粒钙化状较多见(5个病灶).增强后病灶均呈明显不均匀强化,实性部分明显强化(强化幅度>40 HU);平扫及增强后病灶与对侧胸锁乳突肌CT值比值分别为0.69~0.82(0.76±0.18),1.25~1.41(1.33±0.28).伴颈部淋巴结肿大者6例,增强后不规则环形强化或均匀明显强化,1例淋巴结内见砂粒状钙化.结论 直径较大、单发、粗颗粒钙化、甲状腺包膜不完整,并见坏死及明显不均匀强化伴颈部肿大淋巴结是甲状腺间变癌CT较为特征性的表现.%Objective To investigate the CT characteristics of anaplastic thyroid carcinoma and evaluate the diagnostic value of CT in this disease.Methods The CT findings of 10 patients with pathologically proved anaplastic thyroid carcinoma were retrospectively reviewed.The patients included 7 females and 3 males.Their age ranged from 25.0 to 78 years with median of 61 years.Multi-slices plain and post contrast CT scans were performed in all patients.Results Unilateral thyroid was involved in 6 patients.Unilateral thyroid and thyroid isthmus were both involved in 2 patients due to big size.Bilateral thyroid were involved in 2 patients.The maximum diameter of anaplastic thyroid carcinoma ranged from 2.9-12.8 cm with mean of (4.5 ± 1.4) cm.All lesions demonstrated unclear margins and envelope invasion

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

    Science.gov (United States)

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

    2015-01-01

    Abstract Multifocal cerebral gliomas (MCGs) represent approximately 10% of gliomas and are frequently mistaken as metastases of an unknown primary cancer site. Most MCGs are glioblastomas with <4 lesions supratentorially, and are lack of typical symptoms and special detections. Through a rare MCG case, we aim to present this rarity and emphasize the need to correctly diagnose multiple intracranial lesions using a variety of diagnostic modalities to ensure that the patient receives proper treatment. We present a case of multifocal cerebral anaplastic astrocytomas with a total of 8 lesions located in the left frontal lobe and invading the lateral ventricle, presenting with dysphasia and phantosmia. The disease course, including diagnosis and treatment, is presented and analyzed in detail. The pertinent literature is reviewed regarding this uncommon entity. After an initial impression of brain metastasis from lung cancer because of the magnetic resonance imaging (MRI) resemblance and history of chronic bronchitis, we were able to use positron emission tomography (PET) and excisional biopsy to get the final diagnosis. After 10 months, the patient's overall condition deteriorated and succumbed to his disease. MCGs are easy to be misdiagnosed as metastatic diseases. In addition to MRI, PET adds more biochemical and molecular information and is helpful in the differentiation. Although uncommon, if multiple lesions are present in various locations in the hemispheres, MCG should be kept in mind. PMID:25997068

  5. Multiple metastases to the small bowel from large cell bronchial carcinomas

    Institute of Scientific and Technical Information of China (English)

    Davor Tomas; Mario Ledinsky; Mladen Belicza; Bozo Kru(s)lin

    2005-01-01

    AIM: Metastases from lung cancer to gastrointestinal tract are not rare atpostmortem studies but the development of clinically significant symptoms from the gastrointestinal metastases is very unusual.METHODS: Formalin-fixed, paraffin-embedded tissues were cut into 5 μm thick sections and routinely stained with hematoxylin and eosin. Some slides were also stained with Alcian-PAS. Antibodies used were primary antibodies to pancytokeratin, cytokeratin 7, cytokeratin 20, epithelial membrane antigen, vimentin, smooth muscle actin and CD-117.RESULTS: We observed three patients who presented with multiple metastases from large cell bronchial carcinoma to small intestine. Two of them had abdominal symptoms (sudden onset of abdominal pain, constipation and vomiting) and in one case the tumor was incidentally found during autopsy. Microscopically, all tumors showed a same histological pattern and consisted almost exclusively of strands and sheets of poorly cohesive, polymorphic giant cells with scanty, delicate stromas. Few smaller polygonal anaplastic cells dispersed between polymorphic giant cells,were also observed. Immunohistochemistry showed positive staining of the tumor cells with cytokeratin and vimentin. Microscopically and immunohistochemically all metastases had a similar pattern to primary anaplastic carcinoma of the small intestine.CONCLUSION: In patients with small intestine tumors showing anaplastic features, especially with multiple tumors, metastases from large cell bronchial carcinoma should be first excluded, because it seems that they are more common than expected.

  6. A novel, diffusely infiltrative xenograft model of human anaplastic oligodendroglioma with mutations in FUBP1, CIC, and IDH1.

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    Barbara Klink

    Full Text Available Oligodendroglioma poses a biological conundrum for malignant adult human gliomas: it is a tumor type that is universally incurable for patients, and yet, only a few of the human tumors have been established as cell populations in vitro or as intracranial xenografts in vivo. Their survival, thus, may emerge only within a specific environmental context. To determine the fate of human oligodendroglioma in an experimental model, we studied the development of an anaplastic tumor after intracranial implantation into enhanced green fluorescent protein (eGFP positive NOD/SCID mice. Remarkably after nearly nine months, the tumor not only engrafted, but it also retained classic histological and genetic features of human oligodendroglioma, in particular cells with a clear cytoplasm, showing an infiltrative growth pattern, and harboring mutations of IDH1 (R132H and of the tumor suppressor genes, FUBP1 and CIC. The xenografts were highly invasive, exhibiting a distinct migration and growth pattern around neurons, especially in the hippocampus, and following white matter tracts of the corpus callosum with tumor cells accumulating around established vasculature. Although tumors exhibited a high growth fraction in vivo, neither cells from the original patient tumor nor the xenograft exhibited significant growth in vitro over a six-month period. This glioma xenograft is the first to display a pure oligodendroglioma histology and expression of R132H. The unexpected property, that the cells fail to grow in vitro even after passage through the mouse, allows us to uniquely investigate the relationship of this oligodendroglioma with the in vivo microenvironment.

  7. miR-4295 promotes cell proliferation and invasion in anaplastic thyroid carcinoma via CDKN1A

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    Shao, Mingchen; Geng, Yiwei [Oncology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou (China); Laboratory of Tumor Biology, Zhengzhou University, Zhengzhou (China); Lu, Peng [Gastrointestinal Surgery Department, People' s Hospital of Zhengzhou, Zhengzhou (China); Xi, Ying [Oncology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou (China); Laboratory of Tumor Biology, Zhengzhou University, Zhengzhou (China); Wei, Sidong [Liver Transplantation Hepatobiliary Surgery Department, People' s Hospital of Zhengzhou, Zhengzhou (China); Wang, Liuxing; Fan, Qingxia [Oncology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou (China); Laboratory of Tumor Biology, Zhengzhou University, Zhengzhou (China); Ma, Wang, E-mail: doctormawang@126.com [Oncology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou (China); Laboratory of Tumor Biology, Zhengzhou University, Zhengzhou (China)

    2015-09-04

    MicroRNAs (miRNAs) play important roles in the pathogenesis of many types of cancers by negatively regulating gene expression at posttranscriptional level. However, the role of microRNAs in anaplastic thyroid carcinoma (ATC), has remained elusive. Here, we identified that miR-4295 promotes ATC cell proliferation by negatively regulates its target gene CDKN1A. In ATC cell lines, CCK-8 proliferation assay indicated that the cell proliferation was promoted by miR-4295, while miR-4295 inhibitor significantly inhibited the cell proliferation. Transwell assay showed that miR-4295 mimics significantly promoted the migration and invasion of ATC cells, whereas miR-4295 inhibitors significantly reduced cell migration and invasion. luciferase assays confirmed that miR-4295 directly bound to the 3'untranslated region of CDKN1A, and western blotting showed that miR-4295 suppressed the expression of CDKN1A at the protein levels. This study indicated that miR-4295 negatively regulates CDKN1A and promotes proliferation and invasion of ATC cell lines. Thus, miR-4295 may represent a potential therapeutic target for ATC intervention. - Highlights: • miR-4295 mimics promote the proliferation and invasion of ATC cells. • miR-4295 inhibitors inhibit the proliferation and invasion of ATC cells. • miR-4295 targets 3′UTR of CDKN1A in ATC cells. • miR-4295 negatively regulates CDKN1A in ATC cells.

  8. Anaplastic lymphoma kinase gene copy number gain in inflammatory breast cancer (IBC: prevalence, clinicopathologic features and prognostic implication.

    Directory of Open Access Journals (Sweden)

    Min Hwan Kim

    Full Text Available Inflammatory breast cancer (IBC is the most aggressive form of breast cancer, and its molecular pathogenesis still remains to be elucidated. This study aimed to evaluate the prevalence and implication of anaplastic lymphoma kinase (ALK copy number change in IBC patients.We retrospectively collected formalin-fixed, paraffin-embedded tumor tissues and medical records of IBC patients from several institutes in Korea. ALK gene copy number change and rearrangement were assessed by fluorescence in situ hybridization (FISH assay, and ALK expression status was evaluated by immunohistochemical (IHC staining.Thirty-six IBC patients including those with HER2 (+ breast cancer (16/36, 44.4% and triple-negative breast cancer (13/36, 36.1% were enrolled in this study. ALK copy number gain (CNG was observed in 47.2% (17/36 of patients, including one patient who harbored ALK gene amplification. ALK CNG (+ patients showed significantly worse overall survival compared to ALK CNG (- patients in univariate analysis (24.9 months vs. 38.1 months, p = 0.033. Recurrence free survival (RFS after curative mastectomy was also significantly shorter in ALK CNG (+ patients than in ALK CNG (- patients (n = 22, 12.7 months vs. 43.3 months, p = 0.016. Multivariate Cox regression analysis with adjustment for HER2 and ER statuses showed significantly poorer RFS for ALK CNG (+ patients (HR 5.63, 95% CI 1.11-28.44, p = 0.037.This study shows a significant presence of ALK CNG in IBC patients, and ALK CNG was associated with significantly poorer RFS.

  9. miR-4295 promotes cell proliferation and invasion in anaplastic thyroid carcinoma via CDKN1A

    International Nuclear Information System (INIS)

    MicroRNAs (miRNAs) play important roles in the pathogenesis of many types of cancers by negatively regulating gene expression at posttranscriptional level. However, the role of microRNAs in anaplastic thyroid carcinoma (ATC), has remained elusive. Here, we identified that miR-4295 promotes ATC cell proliferation by negatively regulates its target gene CDKN1A. In ATC cell lines, CCK-8 proliferation assay indicated that the cell proliferation was promoted by miR-4295, while miR-4295 inhibitor significantly inhibited the cell proliferation. Transwell assay showed that miR-4295 mimics significantly promoted the migration and invasion of ATC cells, whereas miR-4295 inhibitors significantly reduced cell migration and invasion. luciferase assays confirmed that miR-4295 directly bound to the 3'untranslated region of CDKN1A, and western blotting showed that miR-4295 suppressed the expression of CDKN1A at the protein levels. This study indicated that miR-4295 negatively regulates CDKN1A and promotes proliferation and invasion of ATC cell lines. Thus, miR-4295 may represent a potential therapeutic target for ATC intervention. - Highlights: • miR-4295 mimics promote the proliferation and invasion of ATC cells. • miR-4295 inhibitors inhibit the proliferation and invasion of ATC cells. • miR-4295 targets 3′UTR of CDKN1A in ATC cells. • miR-4295 negatively regulates CDKN1A in ATC cells

  10. Stereotactic Radiation Therapy can Safely and Durably Control Sites of Extra-Central Nervous System Oligoprogressive Disease in Anaplastic Lymphoma Kinase-Positive Lung Cancer Patients Receiving Crizotinib

    Energy Technology Data Exchange (ETDEWEB)

    Gan, Gregory N., E-mail: gregory.gan@ucdenver.edu [Department of Radiation Oncology, University of Colorado, Aurora, Colorado (United States); Weickhardt, Andrew J.; Scheier, Benjamin; Doebele, Robert C. [Department of Medical Oncology, University of Colorado, Aurora, Colorado (United States); Gaspar, Laurie E.; Kavanagh, Brian D. [Department of Radiation Oncology, University of Colorado, Aurora, Colorado (United States); Camidge, D. Ross [Department of Medical Oncology, University of Colorado, Aurora, Colorado (United States)

    2014-03-15

    Purpose: To analyze the durability and toxicity of radiotherapeutic local ablative therapy (LAT) applied to extra-central nervous system (eCNS) disease progression in anaplastic lymphoma kinase-positive non-small cell lung cancer (NSCLC) patients. Methods and Materials: Anaplastic lymphoma kinase-positive NSCLC patients receiving crizotinib and manifesting ≤4 discrete sites of eCNS progression were classified as having oligoprogressive disease (OPD). If subsequent progression met OPD criteria, additional courses of LAT were considered. Crizotinib was continued until eCNS progression was beyond OPD criteria or otherwise not suitable for further LAT. Results: Of 38 patients, 33 progressed while taking crizotinib. Of these, 14 had eCNS progression meeting OPD criteria suitable for radiotherapeutic LAT. Patients with eCNS OPD received 1-3 courses of LAT with radiation therapy. The 6- and 12-month actuarial local lesion control rates with radiation therapy were 100% and 86%, respectively. The 12-month local lesion control rate with single-fraction equivalent dose >25 Gy versus ≤25 Gy was 100% versus 60% (P=.01). No acute or late grade >2 radiation therapy-related toxicities were observed. Median overall time taking crizotinib among those treated with LAT versus those who progressed but were not suitable for LAT was 28 versus 10.1 months, respectively. Patients continuing to take crizotinib for >12 months versus ≤12 months had a 2-year overall survival rate of 72% versus 12%, respectively (P<.0001). Conclusions: Local ablative therapy safely and durably eradicated sites of individual lesion progression in anaplastic lymphoma kinase-positive NSCLC patients receiving crizotinib. A dose–response relationship for local lesion control was observed. The suppression of OPD by LAT in patients taking crizotinib allowed an extended duration of exposure to crizotinib, which was associated with longer overall survival.

  11. Stereotactic Radiation Therapy can Safely and Durably Control Sites of Extra-Central Nervous System Oligoprogressive Disease in Anaplastic Lymphoma Kinase-Positive Lung Cancer Patients Receiving Crizotinib

    International Nuclear Information System (INIS)

    Purpose: To analyze the durability and toxicity of radiotherapeutic local ablative therapy (LAT) applied to extra-central nervous system (eCNS) disease progression in anaplastic lymphoma kinase-positive non-small cell lung cancer (NSCLC) patients. Methods and Materials: Anaplastic lymphoma kinase-positive NSCLC patients receiving crizotinib and manifesting ≤4 discrete sites of eCNS progression were classified as having oligoprogressive disease (OPD). If subsequent progression met OPD criteria, additional courses of LAT were considered. Crizotinib was continued until eCNS progression was beyond OPD criteria or otherwise not suitable for further LAT. Results: Of 38 patients, 33 progressed while taking crizotinib. Of these, 14 had eCNS progression meeting OPD criteria suitable for radiotherapeutic LAT. Patients with eCNS OPD received 1-3 courses of LAT with radiation therapy. The 6- and 12-month actuarial local lesion control rates with radiation therapy were 100% and 86%, respectively. The 12-month local lesion control rate with single-fraction equivalent dose >25 Gy versus ≤25 Gy was 100% versus 60% (P=.01). No acute or late grade >2 radiation therapy-related toxicities were observed. Median overall time taking crizotinib among those treated with LAT versus those who progressed but were not suitable for LAT was 28 versus 10.1 months, respectively. Patients continuing to take crizotinib for >12 months versus ≤12 months had a 2-year overall survival rate of 72% versus 12%, respectively (P<.0001). Conclusions: Local ablative therapy safely and durably eradicated sites of individual lesion progression in anaplastic lymphoma kinase-positive NSCLC patients receiving crizotinib. A dose–response relationship for local lesion control was observed. The suppression of OPD by LAT in patients taking crizotinib allowed an extended duration of exposure to crizotinib, which was associated with longer overall survival

  12. Immunoexpression of TTF-1 and Ki-67 in a coexistent anaplastic and follicular thyroid cancer with rare long-life surviving.

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    Jerzy Sowinski

    2009-01-01

    Full Text Available We report the immunohistochemical diagnosis, including TTF-1 (thyroid transcription factor 1 and Ki-67, of a rare mixed thyroid neoplasm composed of minimally invasive well differentiated follicular areas and highly aggressive undifferentiated anaplastic areas. A 75 old female presented to our clinic with a rapidly growing neck mass. Considering the dynamics of the disease and the multiple challenges presented by the patient: advanced age, tumor size, history of a longstanding goiter we decided to transfer her to the department of surgery. The intraoperative findings were an enlarged right lobe with tracheal and surrounding tissues infiltration. Total thyroidectomy, radical neck lymph nodes dissection and tracheostomy were performed. The histopathological and immunohistochemical examination revealed a coexistent anaplastic and follicular thyroid carcinoma. The proliferation index Ki-67, a cell proliferation marker, was found to be significantly higher in the anaplastic areas (30 +/- 5% in the comparison with the follicular areas (2 +/- 1%. The evaluation of the thyroid transcription factor 1 (TTF-1 expression revealed a correlation with the tumor cells aggressiveness accordingly to the cancer areas. After a radical surgery an external adjuvant radiation was applied. The patient is alive and more than five years after diagnosis she presented an increase of the serum thyroglobulin level suggesting, probably, a recurrence of the follicular form of the cancer. According to our survey we suggest that in thyroid cancers TTF-1 and Ki-67 could provides useful information on the differentiation activities of thyroid tumor cells and may be helpful to distinguish well differentiated and undifferentiated areas in a mixed thyroid cancer.

  13. Successful radiation treatment of anaplastic thyroid carcinoma metastatic to the right cardiac atrium and ventricle in a pacemaker-dependent patient

    International Nuclear Information System (INIS)

    Anaplastic thyroid carcinoma (ATC) is a rare, aggressive malignancy, which is known to metastasize to the heart. We report a case of a patient with ATC with metastatic involvement of the pacemaker leads within the right atrium and right ventricle. The patient survived external beam radiation treatment to his heart, with a radiographic response to treatment. Cardiac metastases are usually reported on autopsy; to our knowledge, this is the first report of the successful treatment of cardiac metastases encasing the leads of a pacemaker, and of cardiac metastases from ATCs, with a review of the pertinent literature

  14. Plastic surgery for large wound defects using vascularized flops in treatment of skin and soft-tissue tumors

    International Nuclear Information System (INIS)

    The results were presented on plastic and reconstructive -anaplastic surgery in resection of locally spread and relapse tumors of the skin and soft tissues after multiple courses of radiation and combined treatment. 38 patients with skin melanoma and softtissue sarcomas received radio- and/or chemotherapy in preoperative period under conditions of local hyperthermia of the tumor. Two types of plasty of large wound defects using vascularized flaps were considered

  15. Alterations of the tumor suppressor genes CDKN2A (p16(INK4a)), p14(ARF), CDKN2B (p15(INK4b)), and CDKN2C (p18(INK4c)) in atypical and anaplastic meningiomas.

    Science.gov (United States)

    Boström, J; Meyer-Puttlitz, B; Wolter, M; Blaschke, B; Weber, R G; Lichter, P; Ichimura, K; Collins, V P; Reifenberger, G

    2001-08-01

    We investigated 67 meningothelial tumors (20 benign meningiomas, 34 atypical meningiomas, and 13 anaplastic meningiomas) for losses of genetic information from chromosome arms 1p and 9p, as well as for deletion, mutation, and expression of the tumor suppressor genes CDKN2A (p16(INKa)/MTS1), p14(ARF), CDKN2B (p15(INK4b)/MTS2) (all located at 9p21) and CDKN2C (1p32). Comparative genomic hybridization and microsatellite analysis showed losses on 1p in 11 anaplastic meningiomas (85%), 23 atypical meningiomas (68%), and 5 benign meningiomas (25%). One atypical meningioma with loss of heterozygosity on 1p carried a somatic CDKN2C mutation (c.202C>T: R68X). Losses on 9p were found in five anaplastic meningiomas (38%), six atypical meningiomas (18%), and one benign meningioma (5%). Six anaplastic meningiomas (46%) and one atypical meningioma (3%) showed homozygous deletions of the CDKN2A, p14(ARF), and CDKN2B genes. Two anaplastic meningiomas carried somatic point mutations in CDKN2A (c.262G>T: E88X and c.262G>A: E88K) and p14(ARF) (c.305G>T: G102V and c.305G>A: G102E). One anaplastic meningioma, three atypical meningiomas, and one benign meningioma without a demonstrated homozygous deletion or mutation of CDKN2A, p14(ARF), or CDKN2B lacked detectable transcripts from at least one of these genes. Hypermethylation of CDKN2A, p14(ARF), and CDKN2B could be demonstrated in one of these cases. Taken together, our results indicate that CDKN2C is rarely altered in meningiomas. However, the majority of anaplastic meningiomas either show homozygous deletions of CDKN2A, p14(ARF), and CDKN2B, mutations in CDKN2A and p14(ARF), or lack of expression of one or more of these genes. Thus, inactivation of the G(1)/S-phase cell-cycle checkpoint is an important aberration in anaplastic meningiomas. PMID:11485924

  16. In vitro identification and characterization of CD133(pos cancer stem-like cells in anaplastic thyroid carcinoma cell lines.

    Directory of Open Access Journals (Sweden)

    Giovanni Zito

    Full Text Available BACKGROUND: Recent publications suggest that neoplastic initiation and growth are dependent on a small subset of cells, termed cancer stem cells (CSCs. Anaplastic Thyroid Carcinoma (ATC is a very aggressive solid tumor with poor prognosis, characterized by high dedifferentiation. The existence of CSCs might account for the heterogeneity of ATC lesions. CD133 has been identified as a stem cell marker for normal and cancerous tissues, although its biological function remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: ATC cell lines ARO, KAT-4, KAT-18 and FRO were analyzed for CD133 expression. Flow cytometry showed CD133(pos cells only in ARO and KAT-4 (64+/-9% and 57+/-12%, respectively. These data were confirmed by qRT-PCR and immunocytochemistry. ARO and KAT-4 were also positive for fetal marker oncofetal fibronectin and negative for thyrocyte-specific differentiating markers thyroglobulin, thyroperoxidase and sodium/iodide symporter. Sorted ARO/CD133(pos cells exhibited higher proliferation, self-renewal, colony-forming ability in comparison with ARO/CD133(neg. Furthermore, ARO/CD133(pos showed levels of thyroid transcription factor TTF-1 similar to the fetal thyroid cell line TAD-2, while the expression in ARO/CD133(neg was negligible. The expression of the stem cell marker OCT-4 detected by RT-PCR and flow cytometry was markedly higher in ARO/CD133(pos in comparison to ARO/CD133(neg cells. The stem cell markers c-KIT and THY-1 were negative. Sensitivity to chemotherapy agents was investigated, showing remarkable resistance to chemotherapy-induced apoptosis in ARO/CD133(pos when compared with ARO/CD133(neg cells. CONCLUSIONS/SIGNIFICANCE: We describe CD133(pos cells in ATC cell lines. ARO/CD133(pos cells exhibit stem cell-like features--such as high proliferation, self-renewal ability, expression of OCT-4--and are characterized by higher resistance to chemotherapy. The simultaneous positivity for thyroid specific factor TTF-1 and onfFN suggest

  17. Anaplastic thyroid cancer

    Science.gov (United States)

    ... or MRI of the neck may show a tumor growing from the thyroid gland. A thyroid biopsy makes the diagnosis. An examination ... the thyroid Images ... Saunders; 2016:chap 226. Lai SY, Mandel SJ, Weber RS. Management of thyroid neoplasms. In: Flint PW, Haughey BH, Lund LJ, et ...

  18. TrkAIII Promotes Microtubule Nucleation and Assembly at the Centrosome in SH-SY5Y Neuroblastoma Cells, Contributing to an Undifferentiated Anaplastic Phenotype

    Directory of Open Access Journals (Sweden)

    Antonietta R. Farina

    2013-01-01

    Full Text Available The alternative TrkAIII splice variant is expressed by advanced stage human neuroblastomas (NBs and exhibits oncogenic activity in NB models. In the present study, employing stable transfected cell lines and assays of indirect immunofluorescence, immunoprecipitation, Western blotting, microtubule regrowth, tubulin kinase, and tubulin polymerisation, we report that TrkAIII binds α-tubulin and promotes MT nucleation and assembly at the centrosome. This effect depends upon spontaneous TrkAIII activity, TrkAIII localisation to the centrosome and pericentrosomal area, and the capacity of TrkAIII to bind, phosphorylate, and polymerise tubulin. We propose that this novel role for TrkAIII contributes to MT involvement in the promotion and maintenance of an undifferentiated anaplastic NB cell morphology by restricting and augmenting MT nucleation and assembly at the centrosomal MTOC.

  19. Energy and protein intake and nutritional status in non-surgically treated patients with small cell anaplastic carcinoma of the lung

    International Nuclear Information System (INIS)

    The spontaneous food intake and nutritional status was assessed in 23 patients with small cell anaplastic carcinoma of the lung before and two times during a treatment period of 6 weeks. Radiation therapy was given for 2 weeks followed by a course of chemotherapy and another 2 weeks of radiation therapy. The energy intake decreased during the treatment from 146 to 130 per cent of basal metabolic rate (p>0.10). The protein intake remained unchanged (mean 0.9 g/kg body weight).There were insignificant and small losses of weight, body fat, free body mass and arm muscle circumference, and no changes were seen in serum albumin and serum transferrin. However, 6 patients suffered a weight loss of 5 per cent or more. No correlation existed between the nutritional parameters measured before treatment and the changes during treatment. Patients who suffered a loss of body weight could therefore not be singled out before the treatment. (orig.)

  20. Thrombospondin-1 silencing down-regulates integrin expression levels in human anaplastic thyroid cancer cells with BRAFV600E: new insights in the host tissue adaptation and homeostasis of tumor microenvironment

    OpenAIRE

    CarmeloNucera; PeterM.Sadow; JackLawler

    2013-01-01

    Background and Rationale: Anaplastic thyroid cancer (ATC) is characterized by pleomorphic cells, has a poor prognosis, is highly devastating disease, and is not curable. No reliable biomarkers of metastatic potential, helpful for early diagnosis of ATC and therapeutic response have been found yet. Thrombospondin-1 (TSP-1) plays a fundamental role in cancer progression by regulating cell stromal cross talk in the tumor microenvironment. Goals: Our goal was to understand whether TSP-1 could...

  1. Anaplastic Thyroid Cancer: The Addition of Systemic Chemotherapy to Radiotherapy Led to an Observed Improvement in Survival—A Single Centre Experience and Review of the Literature

    Science.gov (United States)

    Lowe, Natalie M.; Loughran, Sean; Slevin, Nicholas J.; Yap, Beng K.

    2014-01-01

    Introduction. Anaplastic thyroid carcinoma (ATC) is rare yet accounts for up to 50% of all thyroid cancer deaths. This study reviews outcomes of patients with confirmed ATC referred to a tertiary oncology centre plus reviews the literature to explore how poor outcomes may be improved. Materials and Methods. The management and outcomes of 20 patients with ATC were reviewed. Results. Median age at diagnosis was 69.5 years. 19 patients died due to ATC, 40% of whom died from asphyxiation. Median survival for all cases was 59 days. Patients who had previous surgery prior to other treatment modalities had a longer median survival overall compared to those who had not had previous surgery (142 days compared to 59 days) and produced the one long-term survivor. Chemotherapy followed by radiotherapy (without previous surgery) was associated with longer median survival (220 days). Palliative radiotherapy alone did not decrease the rate of death by asphyxiation when compared to other single modality treatments. Conclusion. Multimodality treatment including surgery when feasible remains the best strategy to improve survival and prevent death from asphyxiation in the management of ATC. The addition of chemotherapy to our institutional protocol led to improved survival but prognosis remains very poor. PMID:25184150

  2. Anaplastic Thyroid Cancer: The Addition of Systemic Chemotherapy to Radiotherapy Led to an Observed Improvement in Survival—A Single Centre Experience and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Natalie M. Lowe

    2014-01-01

    Full Text Available Introduction. Anaplastic thyroid carcinoma (ATC is rare yet accounts for up to 50% of all thyroid cancer deaths. This study reviews outcomes of patients with confirmed ATC referred to a tertiary oncology centre plus reviews the literature to explore how poor outcomes may be improved. Materials and Methods. The management and outcomes of 20 patients with ATC were reviewed. Results. Median age at diagnosis was 69.5 years. 19 patients died due to ATC, 40% of whom died from asphyxiation. Median survival for all cases was 59 days. Patients who had previous surgery prior to other treatment modalities had a longer median survival overall compared to those who had not had previous surgery (142 days compared to 59 days and produced the one long-term survivor. Chemotherapy followed by radiotherapy (without previous surgery was associated with longer median survival (220 days. Palliative radiotherapy alone did not decrease the rate of death by asphyxiation when compared to other single modality treatments. Conclusion. Multimodality treatment including surgery when feasible remains the best strategy to improve survival and prevent death from asphyxiation in the management of ATC. The addition of chemotherapy to our institutional protocol led to improved survival but prognosis remains very poor.

  3. The heat shock protein 90 inhibitor SNX5422 has a synergistic activity with histone deacetylase inhibitors in induction of death of anaplastic thyroid carcinoma cells.

    Science.gov (United States)

    Kim, Si Hyoung; Kang, Jun Goo; Kim, Chul Sik; Ihm, Sung-Hee; Choi, Moon Gi; Yoo, Hyung Joon; Lee, Seong Jin

    2016-02-01

    The influence of the heat shock protein 90 (hsp90) inhibitor SNX5422 alone or in combination with the histone deacetylase (HDAC) inhibitors PXD101, suberoylanilide hydroxamic acid (SAHA), and trichostatin A (TSA) on survival of anaplastic thyroid carcinoma (ATC) cells was investigated. In 8505C and CAL62 cells, SNX5422 caused cell death with concomitant changes in the expression of hsp90 client proteins. After treatment of both SNX5422 and PXD101, SAHA and TSA, compared with treatment of SNX5422 alone, cell viability was diminished, whereas inhibition rate and cytotoxic activity were enhanced. All of the combination index values were lower than 1.0, suggesting the synergism between SNX5422 and PXD101, SAHA and TSA in induction of cell death. In cells treated with both SNX5422 and PXD101, SAHA and TSA, compared with cells treated with SNX5422 alone, the protein levels of Akt, phospho-4EBP1, phospho-S6 K, and survivin were diminished, while those of γH2AX, acetyl. histone H3, acetyl. histone H4, cleaved PARP, and cleaved caspase-3 were enhanced. In conclusion, these results demonstrate that SNX5422 has a cytotoxic activity in conjunction with alterations in the expression of hsp90 client proteins in ATC cells. Moreover, SNX5422 synergizes with HDAC inhibitors in induction of cytotoxicity accompanied by the suppression of PI3K/Akt/mTOR signaling and survivin, and the overexpression of DNA damage-related proteins in ATC cells. PMID:26219406

  4. Evaluation of Lentiviral-Mediated Expression of Sodium Iodide Symporter in Anaplastic Thyroid Cancer and the Efficacy of In Vivo Imaging and Therapy

    Directory of Open Access Journals (Sweden)

    Chien-Chih Ke

    2011-01-01

    Full Text Available Anaplastic thyroid carcinoma (ATC is one of the most deadly cancers. With intensive multimodalities of treatment, the survival remains low. ATC is not sensitive to 131I therapy due to loss of sodium iodide symporter (NIS gene expression. We have previously generated a stable human NIS-expressing ATC cell line, ARO, and the ability of iodide accumulation was restored. To make NIS-mediated gene therapy more applicable, this study aimed to establish a lentiviral system for transferring hNIS gene to cells and to evaluate the efficacy of in vitro and in vivo radioiodide accumulation for imaging and therapy. Lentivirus containing hNIS cDNA were produced to transduce ARO cells which do not concentrate iodide. Gene expression, cell function, radioiodide imaging and treatment were evaluated in vitro and in vivo. Results showed that the transduced cells were restored to express hNIS and accumulated higher amount of radioiodide than parental cells. Therapeutic dose of 131I effectively inhibited the tumor growth derived from transduced cells as compared to saline-treated mice. Our results suggest that the lentiviral system efficiently transferred and expressed hNIS gene in ATC cells. The transduced cells showed a promising result of tumor imaging and therapy.

  5. Rapid and dramatic response to alectinib in an anaplastic lymphoma kinase rearranged non-small-cell lung cancer patient who is critically ill.

    Science.gov (United States)

    Yoshida, Tatsuya; Hida, Toyoaki; Yatabe, Yasushi

    2016-07-01

    Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) have shown promising clinical activity in the treatment of non-small-cell lung cancer (NSCLC) that harbors ALK rearrangement. The next-generation ALK-TKI, alectinib, has been reported to have potent efficacy in ALK-positive NSCLC patients including on mutations that confer resistance to crizotinib, which was the first ALK-TKI approved for ALK-positive NSCLC. The efficacy and safety of ALK-TKIs, including crizotinib and alectinib, as the first-line treatment in critically ill patients is unclear. We report one ALK-positive NSCLC patient with poor performance status (PS) and disseminated intravascular coagulation because of respiratory failure and multiple metastases, and experienced the rapid and dramatic response to alectinib without adverse events that can lead to discontinuation and dose reduction of the drug. After a couple of months of treatment with alectinib, radiological review indicated a complete response. The present case is the first reported case of rapid and marked response to alectinib in ALK-positive NSCLC patients who had poor PS and severe organ dysfunction, such as disseminated intravascular coagulation. Further investigation of the safety and efficacy of ALK-TKI for ALK-positive NSCLC patients who are critically ill is warranted. PMID:26938871

  6. Anaplastic Thyroid Carcinoma: A ceRNA Analysis Pointed to a Crosstalk between SOX2, TP53, and microRNA Biogenesis

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    Walter Arancio

    2015-01-01

    Full Text Available It has been suggested that cancer stem cells (CSC may play a central role in oncogenesis, especially in undifferentiated tumours. Anaplastic thyroid carcinoma (ATC has characteristics suggestive of a tumour enriched in CSC. Previous studies suggested that the stem cell factor SOX2 has a preeminent hierarchical role in determining the characteristics of stem cells in SW1736 ATC cell line. In detail, silencing SOX2 in SW1736 is able to suppress the expression of the stem markers analysed, strongly sensitizing the line to treatment with chemotherapeutic agents. Therefore, in order to further investigate the role of SOX2 in ATC, a competing endogenous RNA (ceRNA analysis was conducted in order to isolate new functional partners of SOX2. Among the interactors, of particular interest are genes involved in the biogenesis of miRNAs (DICER1, RNASEN, and EIF2C2, in the control cell cycle (TP53, CCND1, and in mitochondrial activity (COX8A. The data suggest that stemness, microRNA biogenesis and functions, p53 regulatory network, cyclin D1, and cell cycle control, together with mitochondrial activity, might be coregulated.

  7. 伴鳞样成分的甲状腺间变性癌临床病理分析%Clinicopathologic Analysis of Anaplastic Thyroid Carcinoma with Squamoid Cell Component

    Institute of Scientific and Technical Information of China (English)

    潘毅; 孙保存

    2011-01-01

    目的:探讨伴鳞样成分的甲状腺间变性癌(anaplastic thyroid carcinoma with squamoid cell component,ATC-SCC)的诊断、鉴别诊断及临床病理特征.方法:回顾性分析85例少见甲状腺肿瘤的临床病理资料,通过HE切片进行形态学观察,对5例ATC-SCC,6例甲状腺鳞状细胞癌(squamous cell carcinoma,SCC),8例甲状腺呈胸腺样分化癌(carcinoma showing thymus-like ele?ments,CASTLE)和2 例甲状腺降钙素阴性的神经内分泌肿瘤(calcitonin-negative neuroendocrine tumor of the thyroid gland,CNNETT)进行9项免疫组织化学染色,包括Cytokeratin(CK)、Vimentin(VM)、Chromogranin A(CgA)、Synaptophysin(SYN)、CD117、CD5、Calcitonin(CT)、Thyroglobulin(TG)和Thyroid transcription factor-1(TTF-1),并对结果进行分析.结果:5例ATC-SCC中,男性2例,女性3例;年龄41~79岁,平均年龄53.2岁;肿物位于左腺叶3例,右腺叶2例.临床表现为无痛性颈部肿物.肿物通常体积较大,质地硬实,与周围组织粘连.镜下可见肿瘤组织由梭形细胞、多形性巨细胞、破骨样细胞和鳞状上皮样细胞以不同比例混合而成,并可见胞浆红染的横纹肌样细胞及大片坏死.免疫组织化学染色显示5例ATC-SCC的肿瘤细胞CK和VM均阳性.鳞状上皮样细胞为主要成分时需要与SCC、CASTLE和CNNETT进行鉴别.结论:ATC-SCC多见于老年人,女性较多见,生长迅速,常扩展至甲状腺外累犯颈部软组织,预后非常差,手术和放化疗相结合是治疗ATC-SCC的基本原则.%Objective: To investigate the clinicopathologic features, diagnosis, and differential diagnosis of anaplastic thyroid carcinoma with squamoid cell component ( ATC-SCC ).Methods: The data of 85 cases with rare thyroid neoplasms were retrospectively analyzed.Morphological observation of the sections from all cases was conducted after H&E staining.Five cases of ATC-SCC, 6 cases of thyroid squamous cell carcinoma ( TSCC ), 8 cases of with thyroid carcinoma showing thymus

  8. Improved Correlation of the Neuropathologic Classification According to Adapted World Health Organization Classification and Outcome After Radiotherapy in Patients With Atypical and Anaplastic Meningiomas

    International Nuclear Information System (INIS)

    Purpose: To evaluate the correlation between the 1993 and 2000/2007 World Health Organization (WHO) classification with the outcome in patients with high-grade meningiomas. Patients and Methods: Between 1985 and 2004, 73 patients diagnosed with atypical or anaplastic meningiomas were treated with radiotherapy. Sections from the paraffin-embedded tumor material from 66 patients (90%) from 13 different pathology departments were re-evaluated according to the first revised WHO classification from 1993 and the revised classifications from 2000/2007. In 4 cases, the initial diagnosis meningioma was not reproducible (5%). Therefore, 62 patients with meningiomas were analyzed. Results: All 62 tumors were reclassified according to the 1993 and 2000/2007 WHO classification systems. Using the 1993 system, 7 patients were diagnosed with WHO grade I meningioma (11%), 23 with WHO grade II (37%), and 32 with WHO grade III meningioma (52%). After scoring using the 2000/2007 system, we found 17 WHO grade I meningiomas (27%), 32 WHO grade II meningiomas (52%), and 13 WHO grade III meningiomas (21%). According to the 1993 classification, the difference in overall survival was not statistically significant among the histologic subgroups (p = .96). Using the 2000/2007 WHO classifications, the difference in overall survival became significant (p = .02). Of the 62 reclassified patients 29 developed tumor progression (47%). No difference in progression-free survival was observed among the histologic subgroups (p = .44). After grading according to the 2000/2007 WHO classifications, significant differences in progression-free survival were observed among the three histologic groups (p = .005). Conclusion: The new 2000/2007 WHO classification for meningiomas showed an improved correlation between the histologic grade and outcome. This classification therefore provides a useful basis to determine the postoperative indication for radiotherapy. According to our results, a comparison of the

  9. Anaplastic lymphoma kinase gene rearrangements in patients with advanced-stage non-small-cell lung cancer: CT characteristics and response to chemotherapy

    International Nuclear Information System (INIS)

    Few articles have been published on the imaging findings of anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC). To investigate the radiological findings of ALK-positive NSCLC in the advanced stage, CT scans were examined. In addition, the response to chemotherapy was evaluated. Of the 36 patients with ALK-rearranged NSCLC, a mass and a nodule were identified in 17 (47.2%) and 16 (44.4%), respectively, indicating that more than 40% had a small-sized tumor. Overall, 31 (86.1%) patients had lymphadenopathy, seven (19.4%) had extranodal lymph node invasion, and three (8.3%) had lymphangitis. A pleural effusion was seen in 15 patients (41.7%). All but one patient had no ground-glass opacity (GGO) lesions, indicating that most ALK-positive tumors showed a solid growth pattern without GGO on CT. Twenty were evaluable for response to chemotherapy; 10 (50.0%) had a partial response (PR), nine (45.0%) had stable disease (SD), and one (5.0%) had progressive disease (PD) with first-line chemotherapy. With second-line chemotherapy, five (26.3%) had PR, 11 (57.9%) had SD, and three (15.8%) had PD. The five patients with PR were all treated by using crizotinib. Time to progression was 8.2 months with first-line chemotherapy, and 6.0 months with second-line chemotherapy. Advanced-stage ALK-positive tumors have a relatively aggressive phenotype, which cannot be inferred from the size of the tumor alone. ALK-positive patients have a good response to first-line cytotoxic drugs and to crizotinib as second-line therapy, but a relatively poor response to cytotoxic drugs as second-line therapy

  10. Rearranged anaplastic lymphoma kinase (ALK) gene found for the first time in adult-onset papillary thyroid cancer cases among atomic bomb survivors

    Energy Technology Data Exchange (ETDEWEB)

    Hamatani, K.; Mukai, M.; Takahashi, K.; Nakachi, K.; Kusunoki, Y. [Radiobiology/Molecular Epidemiology, Radiation Effects Research Foundation, Hiroshima (Japan); Hayashi, Y. [Geriatric Health Service Facility Hidamari, Hiroshima (Japan)

    2012-07-01

    Full text of the publication follows: Thyroid cancer is one of the malignancies most strongly associated with ionizing radiation in humans. Epidemiology studies of atomic bomb (A-bomb) survivors have indicated that excess relative risk of papillary thyroid cancer per Gy was remarkably high in the survivors. We therefore aim to clarify mechanisms linking A-bomb radiation exposure and development of papillary thyroid cancer. Toward this end, we intend to clarify characteristics of gene alterations occurring in radiation-associated adult-onset papillary thyroid cancer from the Life Span Study cohort of A-bomb survivors. We have thus far found that with increased radiation dose, papillary thyroid cancer cases with chromosomal rearrangements (mainly RET/PTC rearrangements) significantly increased and papillary thyroid cancer cases with point mutations (mainly BRAF-V600E) significantly decreased. Papillary thyroid cancer cases with non-detected gene alterations that carried no mutations in RET, NTRK1, BRAF or RAS genes tended to increase with increased radiation dose. In addition, we found that relative frequency of these papillary thyroid cancer cases significantly decreased with time elapsed since exposure. Through analysis of papillary thyroid cancer cases with non-detected gene alterations, we recently discovered a new type of rearrangement for the first time in papillary thyroid cancer, i.e., rearranged anaplastic lymphoma kinase (ALK) gene, although identification of any partner gene(s) is needed. Specifically, rearrangement of ALK was found in 10 of 19 exposed papillary thyroid cancer cases with non-detected gene alterations but not in any of the six non-exposed papillary thyroid cancer cases. Furthermore, papillary thyroid cancer with ALK rearrangement was frequently found in the cases with high radiation dose or with short time elapsed since A-bomb exposure. These results suggest that chromosomal rearrangement, typically of RET and ALK, may play an important

  11. Contrast enhancement in 1p/19q-codeleted anaplastic oligodendrogliomas is associated with 9p loss, genomic instability, and angiogenic gene expression

    Science.gov (United States)

    Reyes-Botero, German; Dehais, Caroline; Idbaih, Ahmed; Martin-Duverneuil, Nadine; Lahutte, Marion; Carpentier, Catherine; Letouzé, Eric; Chinot, Olivier; Loiseau, Hugues; Honnorat, Jerome; Ramirez, Carole; Moyal, Elisabeth; Figarella-Branger, Dominique; Ducray, François; Desenclos, Christine; Sevestre, Henri; Menei, Philippe; Michalak, Sophie; Al Nader, Edmond; Godard, Joel; Viennet, Gabriel; Carpentier, Antoine; Eimer, Sandrine; Dam-Hieu, Phong; Quintin-Roué, Isabelle; Guillamo, Jean-Sebastien; Lechapt-Zalcman, Emmanuelle; Kemeny, Jean-Louis; Verrelle, Pierre; Faillot, Thierry; Gaultier, Claude; Tortel, Marie Christine; Christov, Christo; Le Guerinel, Caroline; Aubriot-Lorton, Marie-Hélène; Ghiringhelli, Francois; Berger, François; Lacroix, Catherine; Parker, Fabrice; Dubois, François; Maurage, Claude-Alain; Gueye, Edouard-Marcel; Labrousse, Francois; Jouvet, Anne; Bauchet, Luc; Rigau, Valérie; Beauchesne, Patrick; Vignaud, Jean-Michel; Campone, Mario; Loussouarn, Delphine; Fontaine, Denys; Vandenbos, Fanny; Campello, Chantal; Roger, Pascal; Fesneau, Melanie; Heitzmann, Anne; Delattre, Jean-Yves; Elouadhani, Selma; Mokhtari, Karima; Polivka, Marc; Ricard, Damien; Levillain, Pierre-Marie; Wager, Michel; Colin, Philippe; Diebold, Marie-Danièle; Chiforeanu, Dan; Vauleon, Elodie; Langlois, Olivier; Laquerriere, Annie; Motsuo Fotso, Marie Janette; Peoc'h, Michel; Andraud, Marie; Mouton, Servane; Chenard, Marie-Pierre; Noel, Georges; Desse, Nicolas; Soulard, Raoulin; Amiel-Benouaich, Alexandra; Uro-Coste, Emmanuelle; Dhermain, Frederic

    2014-01-01

    Background The aim of this study was to correlate MRI features and molecular characteristics in anaplastic oligodendrogliomas (AOs). Methods The MRI characteristics of 50 AO patients enrolled in the French national network for high-grade oligodendroglial tumors were analyzed. The genomic profiles and IDH mutational statuses were assessed using high-resolution single-nucleotide polymorphism arrays and direct sequencing, respectively. The gene expression profiles of 25 1p/19q-codeleted AOs were studied on Affymetrix expression arrays. Results Most of the cases were frontal lobe contrast-enhanced tumors (52%), but the radiological presentations of these cases were heterogeneous, ranging from low-grade glioma-like aspects (26%) to glioblastoma-like aspects (22%). The 1p/19q codeletion (n = 39) was associated with locations in the frontal lobe (P = .001), with heterogeneous intratumoral signal intensities (P = .003) and with no or nonmeasurable contrast enhancements (P = .01). The IDH wild-type AOs (n = 7) more frequently displayed ringlike contrast enhancements (P = .03) and were more frequently located outside of the frontal lobe (P = .01). However, no specific imaging pattern could be identified for the 1p/19q-codeleted AO or the IDH-mutated AO. Within the 1p/19q-codeleted AO, the contrast enhancement was associated with larger tumor volumes (P = .001), chromosome 9p loss and CDKN2A loss (P = .006), genomic instability (P = .03), and angiogenesis-related gene expression (P < .001), particularly for vascular endothelial growth factor A and angiopoietin 2. Conclusion In AOs, the 1p/19q codeletion and the IDH mutation are associated with preferential (but not with specific) imaging characteristics. Within 1p/19q-codeleted AO, imaging heterogeneity is related to additional molecular alterations, especially chromosome 9p loss, which is associated with contrast enhancement and larger tumor volume. PMID:24353325

  12. Rearranged anaplastic lymphoma kinase (ALK) gene found for the first time in adult-onset papillary thyroid cancer cases among atomic bomb survivors

    International Nuclear Information System (INIS)

    Full text of the publication follows: Thyroid cancer is one of the malignancies most strongly associated with ionizing radiation in humans. Epidemiology studies of atomic bomb (A-bomb) survivors have indicated that excess relative risk of papillary thyroid cancer per Gy was remarkably high in the survivors. We therefore aim to clarify mechanisms linking A-bomb radiation exposure and development of papillary thyroid cancer. Toward this end, we intend to clarify characteristics of gene alterations occurring in radiation-associated adult-onset papillary thyroid cancer from the Life Span Study cohort of A-bomb survivors. We have thus far found that with increased radiation dose, papillary thyroid cancer cases with chromosomal rearrangements (mainly RET/PTC rearrangements) significantly increased and papillary thyroid cancer cases with point mutations (mainly BRAF-V600E) significantly decreased. Papillary thyroid cancer cases with non-detected gene alterations that carried no mutations in RET, NTRK1, BRAF or RAS genes tended to increase with increased radiation dose. In addition, we found that relative frequency of these papillary thyroid cancer cases significantly decreased with time elapsed since exposure. Through analysis of papillary thyroid cancer cases with non-detected gene alterations, we recently discovered a new type of rearrangement for the first time in papillary thyroid cancer, i.e., rearranged anaplastic lymphoma kinase (ALK) gene, although identification of any partner gene(s) is needed. Specifically, rearrangement of ALK was found in 10 of 19 exposed papillary thyroid cancer cases with non-detected gene alterations but not in any of the six non-exposed papillary thyroid cancer cases. Furthermore, papillary thyroid cancer with ALK rearrangement was frequently found in the cases with high radiation dose or with short time elapsed since A-bomb exposure. These results suggest that chromosomal rearrangement, typically of RET and ALK, may play an important

  13. Targeting Transforming Growth Factor-Beta1 (TGF-β1) Inhibits Tumorigenesis of Anaplastic Thyroid Carcinoma Cells Through ERK1/2-NFκkB-PUMA Signaling.

    Science.gov (United States)

    Yin, Qiang; Liu, Shan; Dong, Anbing; Mi, Xiufang; Hao, Fengyun; Zhang, Kejun

    2016-01-01

    BACKGROUND The transforming growth factor-beta (TGF-β) signaling pathway plays a critical role in promoting tumor growth. TGF-β1was found to be overexpressed in anaplastic thyroid cancer (ATC). We therefore tested our hypothesis that targeting TGF-β1 inhibits tumorigenesis of ATC cells. MATERIAL AND METHODS Effects of TGF-β1 stimulation or TGF-β1 inhibition by small interfering RNA (TGF-β1siRNA) on proliferation, colony formation, and apoptosis in 8505C cells in vitro was detected using siRNAs and inhibitors to examine the TGF-β1 signaling pathway. A subcutaneously implanted tumor model of 8505C cells in nude mice was used to assess the effects of TGF-β1 inhibition on tumorigenesis development. RESULTS TGF-β1siRNAs decreased proliferation and colony formation, and increased apoptosis in 8505C cells in vitro and inhibited tumor growth in vivo. TGF-β1siRNA inhibited phosphorylation ERK1/2 (pERK1/2) and increased p65-dependant PUMA mRNA and protein expression. Knockdown of p65 or PUMA by siRNA reduced TGF-β1siRNA-induced apoptosis, as well as caspase-3 and PARP activation. Upregulation of p65 or PUMA expression by TGF-β1siRNA requires pERK1/2 inhibition. TGF-β1 shRNA inhibited tumor growth in vivo. CONCLUSIONS Therapies targeting the TGF-β1 pathway may be more effective to prevent primary tumor formation. The ability of this therapy to decrease tumorigenesis may be related to ERK1/2/NF-κB/PUMA signaling. PMID:27356491

  14. Influence of an oligodendroglial component on the survival of patients with anaplastic astrocytomas: a report of radiation therapy oncology group 83-02

    International Nuclear Information System (INIS)

    Purpose: Seven percent of patients with high grade gliomas enrolled in RTOG 83-02 had mixed astrocytoma/oligodenroglial elements on central pathology review. It has often been assumed that the most aggressive histologic component of a tumor determines biologic behavior; however in this trial, the survival of patients who had mixed glioblastomas/oligodenrogliomas was significantly longer than that of patients with pure glioblastomas (GBM). We therefore evaluated the effect of an oligodendroglial component on the survival of patients who had anaplastic astrocytomas (AAF) treated in the same trial. Methods and Materials: One hundred nine patients who had AAF and 24 patients with mixed AAF/oligodendrogliomas (AAF/OL) were enrolled in a Phase I/II trial of randomized dose-escalation hyper fractioned radiotherapy plus BCNU. AAF/OL patients were older and more likely to have had more aggressive surgery than AAF patients. Other pretreatment characteristics were balanced between groups, as was assigned treatment. Results: The median survival time for AAF was 3.0 years versus 7.3 years for AAF/OL (p = 0.019). In a multivariate analysis, adjusting for extent of surgical resection and age, an oligodendroglial component was an independent prognostic factor for survival. Conclusion: The results support the concept that AAFs with an oligodendroglial component have a better prognosis than pure AAF tumors, similar to the effect seen among patients with glioblastoma multiforme tumors. This better survival outcome should be taken into consideration in the design and stratification of future trials. Additionally, in contrast to patients with GBMs, patients who have AAF/OL have the potential for prolonged survival; therefore, late sequelae of treatment (both radiation and chemotherapy) must be weighed more heavily in the benefits to risks analysis

  15. Cognition and Quality of Life After Chemotherapy Plus Radiotherapy (RT) vs. RT for Pure and Mixed Anaplastic Oligodendrogliomas: Radiation Therapy Oncology Group Trial 9402

    International Nuclear Information System (INIS)

    Purpose: Radiation Therapy Oncology Group 9402 compared procarbazine, lomustine, and vincristine (PCV) chemotherapy plus radiation therapy (PCV + RT) vs. RT alone for anaplastic oligodendroglioma. Here we report longitudinal changes in cognition and quality of life, effects of patient factors and treatments on cognition, quality of life and survival, and prognostic implications of cognition and quality of life. Methods and Materials: Cognition was assessed by Mini Mental Status Examination (MMSE) and quality of life by Brain-Quality of Life (B-QOL). Scores were analyzed for survivors and within 5 years of death. Shared parameter models evaluated MMSE/B-QOL with survival. Results: For survivors, MMSE and B-QOL scores were similar longitudinally and between treatments. For those who died, MMSE scores remained stable initially, whereas B-QOL slowly declined; both declined rapidly in the last year of life and similarly between arms. In the aggregate, scores decreased over time (p = 0.0413 for MMSE; p = 0.0016 for B-QOL) and were superior with age <50 years (p < 0.001 for MMSE; p = 0.0554 for B-QOL) and Karnofsky Performance Score (KPS) 80-100 (p < 0.001). Younger age and higher KPS were associated with longer survival. After adjusting for patient factors and drop-out, survival was longer after PCV + RT (HR = 0.66, 95% CI = 0.49-0.9, p = 0.0084; HR = 0.74, 95% CI = 0.54-1.01, p = 0.0592) in models with MMSE and B-QOL. In addition, there were no differences in MMSE and B-QOL scores between arms (p = 0.4752 and p = 0.2767, respectively); higher scores predicted longer survival. Conclusion: MMSE and B-QOL scores held steady in the upper range in both arms for survivors. Younger, fitter patients had better MMSE and B-QOL and longer survival.

  16. Anaplastic, plasmablastic, and plasmacytic plasmacytomas of mice: relationships to human plasma cell neoplasms and late-stage differentiation of normal B cells.

    Science.gov (United States)

    Qi, Chen-Feng; Zhou, Jeff X; Lee, Chang Hoon; Naghashfar, Zohreh; Xiang, Shao; Kovalchuk, Alexander L; Fredrickson, Torgny N; Hartley, Janet W; Roopenian, Derry C; Davidson, Wendy F; Janz, Siegfried; Morse, Herbert C

    2007-03-15

    We have compared histologic features and gene expression profiles of newly identified plasmacytomas from NFS.V(+) congenic mice with plasmacytomas of IL6 transgenic, Fasl mutant, and SJL-beta2M(-/-) mice. NFS.V(+) tumors comprised an overlapping morphologic spectrum of high-grade/anaplastic, intermediate-grade/plasmablastic, and low-grade/plasmacytic cases with similarities to subsets of human multiple myeloma and plasmacytoma. Microarray and immunohistochemical analyses of genes expressed by the most prevalent tumors, plasmablastic plasmacytomas, showed them to be most closely related to immunoblastic lymphomas, less so to plasmacytomas of Fasl mutant and SJL mice, and least to plasmacytic plasmacytomas of IL6 transgenic mice. Plasmablastic tumors seemed to develop in an inflammatory environment associated with gene signatures of T cells, natural killer cells, and macrophages not seen with plasmacytic plasmacytomas. Plasmablastic plasmacytomas from NFS.V(+) and SJL-beta2M(-/-) mice did not have structural alterations in Myc or T(12;15) translocations and did not express Myc at high levels, regular features of transgenic and pristane-induced plasmacytomas. These findings imply that, as for human multiple myeloma, Myc-independent routes of transformation contribute to the pathogenesis of these tumors. These findings suggest that plasma cell neoplasms of mice and humans exhibit similar degrees of complexity. Mouse plasmacytomas, previously considered to be homogeneous, may thus be as diverse as their human counterparts with respect to oncogenic mechanisms of plasma cell transformation. Selecting specific types of mouse plasmacytomas that relate most closely to subtypes of human multiple myeloma may provide new opportunities for preclinical testing of drugs for treatment of the human disease. PMID:17363561

  17. Molecular and Functional Characterizations of the Association and Interactions between Nucleophosmin-Anaplastic Lymphoma Kinase and Type I Insulin-Like Growth Factor Receptor

    Directory of Open Access Journals (Sweden)

    Bin Shi

    2013-06-01

    Full Text Available Nucleophosmin-anaplastic lymphoma kinase (NPM-ALK is aberrantly expressed in a subset of T cell lymphoma that commonly affects children and young adults. NPM-ALK possesses significant oncogenic potential that was previously documented using in vitro and in vivo experimental models. The exact mechanisms by which NPM-ALK induces its effects are poorly understood. We have recently demonstrated that NPM-ALK is physically associated with type I insulin-like growth factor receptor (IGF-IR. A positive feedback loop appears to exist between NPM-ALK and IGF-IR through which these two kinases interact to potentiate their effects. We have also found that a single mutation of the Tyr644 or Tyr664 residue of the C terminus of NPM-ALK to phenylalanine decreases significantly, but does not completely abolish, the association between NPM-ALK and IGF-IR. The purpose of this study was to determine whether the dual mutation of Tyr644 and Tyr664 abrogates the association and interactions between NPM-ALK and IGF-IR. We also examined the impact of this dual mutation on the oncogenic potential of NPM-ALK. Our results show that NPM-ALKY644,664F completely lacks association with IGF-IR. Importantly, we found that the dual mutation of Tyr644 and Tyr664 diminishes the oncogenic effects of NPM-ALK, including its ability to induce anchorage-independent colony formation and to sustain cellular transformation, proliferation, and migration. Furthermore, the association between NPM-ALK and IGF-IR through Tyr644 and Tyr664 appears to contribute to maintaining the stability of NPM-ALK protein. Our results provide novel insights into the mechanisms by which NPM-ALK induces its oncogenic effects through interactions with IGF-IR in this aggressive lymphoma.

  18. Exploratory evaluation of two-dimensional and three-dimensional methods of FDG PET quantification in pediatric anaplastic astrocytoma: a report from the Pediatric Brain Tumor Consortium (PBTC)

    Energy Technology Data Exchange (ETDEWEB)

    Williams, Gethin; Treves, S. Ted [Harvard Medical School, Joint Program in Nuclear Medicine, Children' s Hospital Boston, Boston, MA (United States); Fahey, Frederic H. [Harvard Medical School, Joint Program in Nuclear Medicine, Children' s Hospital Boston, Boston, MA (United States); Harvard Medical School, Division of Nuclear Medicine, Department of Radiology, Children' s Hospital Boston, Boston, MA (United States); Kocak, Mehmet; Boyett, James M.; Kun, Larry E. [St Jude Children' s Research Hospital, Memphis, TN (United States); Pollack, Ian F. [Children' s Hospital Pittsburgh, Pittsburgh, PA (United States); Young Poussaint, Tina [Harvard Medical School, Division of Neuroradiology, Department of Radiology, Children' s Hospital Boston, Boston, MA (United States)

    2008-09-15

    The rationale of this study was to investigate the feasibility of three-dimensional (3D) methods to analyze {sup 18}F-fluoro-deoxy-glucose (FDG) uptake in children with anaplastic astrocytoma (AA) in a multi-institutional trial, to compare 3D and two-dimensional (2D) methods and explore data associations with progression-free survival (PFS). 3D tumor volumes from pretreatment MR images (fluid attenuation inversion recovery and postgadolinium) of children with recurrent AA on a phase I trial of imatinib mesylate were coregistered to FDG positron emission tomography (PET) images. PET data were normalized. Four metrics were defined: the maximum ratio (maximum pixel value within the 3D tumor volume, normalized), the total ratio (cumulative pixel values within the tumor volume, normalized) and tumor mean ratio (total pixel value divided by volume, normalized). 2D analysis methods were compared. Cox proportional hazards models were used to estimate the association between these methods and PFS. Strongest correlations between 2D and 3D methods were with analyses using postcontrast T1 images for volume of interest (VOI). The analyses suggest 3D maximum tumor and mean tumor ratios, whether normalized by gray matter or white matter, were associated with PFS. This study of a series of pretreatment AA patients suggests that 3D PET methods using VOIs based on postcontrast T1 correlate with 2D methods and are related to PFS. These methods yield an estimate of metabolically active tumor burden and may add prognostic information after tumor grade is determined. Future rigorous multi-institutional protocols with larger numbers of patients will be required for validation. (orig.)

  19. Clinicopathologic characteristics andtherapeutic responses ofChinese patients withnon-small cell lung cancer who harbor an anaplastic lymphoma kinase rearrangement

    Institute of Scientific and Technical Information of China (English)

    ShaFu; HaiYunWang; FangWang; MaYanHuang; LingDeng; XiaoZhang; ZuLuYe; JianYong Shao

    2015-01-01

    Introduction:The rearrangement of the anaplastic lymphoma kinase (ALK) gene accounts for approximately 1%–6%of lung adenocarcinoma cases and deifnes a molecular subgroup of tumors characterized by clinical sensitivity toALK inhibitors such as crizotinib. This study aimed to identify the relationship betweenALK rearrangement and the clinico‑pathologic characteristics of non‑small cell lung cancer (NSCLC) and to analyze the therapeutic responses of crizotinib and conventional chemotherapy toALK rearrangement in NSCLC patients. Methods:A total of 487 lung cancer patients who underwent testing forALK rearrangement in our department were included in this study.ALK rearrangement was examined by using lfuorescence insitu hybridization (FISH) assay. Results:Among the 487 patients, 44 (9.0%) were diagnosed withALK rearrangement by using FISH assay. In 123 patients with adenocarcinoma who were non‑smokers and of a young age (≤58years old), the frequency ofALK rearrangement was 20.3% (25/123). Short overall survival (OS) was associated with non‑adenocarcinoma tumor type (P=0.006), poorly differentiated tumors (P=0.001), advanced‑stage tumors (P<0.001), smoking history (P=0.008), and wild‑type epidermal growth factor receptor (EGFR) (P=0.008). Moreover, patients with poorly differentiated and advanced‑stage tumors had a shorter time to cancer progression compared with those with well differentiated (P=0.023) and early‑stage tumors (P=0.001), respectively. Conclusions:ALK‑rearranged NSCLC tends to occur in younger individuals who are either non‑smokers or light smokers with adenocarcinoma. Patients withALK rearrangement might beneift fromALK inhibitor therapy.

  20. O6-methylguanine-DNA methyltransferase activity is associated with response to alkylating agent therapy and with MGMT promoter methylation in glioblastoma and anaplastic glioma

    Science.gov (United States)

    Bobola, Michael S.; Alnoor, Mohammad; Chen, John Y.-S.; Kolstoe, Douglas D.; Silbergeld, Daniel L.; Rostomily, Robert C.; Blank, A.; Chamberlain, Marc C.; Silber, John R.

    2014-01-01

    Background CpG methylation in the O6-methylguanine-DNA methyltransferase (MGMT) promoter is associated with better outcome following alkylating agent chemotherapy in glioblastoma (GBM) and anaplastic glioma (AG). To what extent improved response reflects low or absent MGMT activity in glioma tissue has not been unequivocally assessed. This information is central to developing anti-resistance therapies. Methods We examined the relationship of MGMT activity in 91 GBMs and 84 AGs with progression-free survival (PFS) following alkylator therapy and with promoter methylation status determined by methylation-specific PCR (MSP). Results Cox regression analysis revealed that GBMs with high activity had a significantly greater risk for progression in dichotomous (P ≤ 0.001) and continuous (P ≤ 0.003) models, an association observed for different alkylator regimens, including concurrent chemo-radiation with temozolomide. Analysis of MGMT promoter methylation status in 47 of the GBMs revealed that methylated tumors had significantly lower activity (P ≤ 0.005) and longer PFS (P ≤ 0.036) compared to unmethylated tumors, despite overlapping activities. PFS was also significantly greater in methylated vs. unmethylated GBMs with comparable activity (P ≤ 0.005), and among unmethylated tumors with less than median activity (P ≤ 0.026), suggesting that mechanisms in addition to MGMT promote alkylator resistance. Similar associations of MGMT activity with PFS and promoter methylation status were observed for AGs. Conclusions Our results provide strong support for the hypotheses that MGMT activity promotes alkylator resistance and reflects promoter methylation status in malignant gliomas. General significance MGMT activity is an attractive target for anti-resistance therapy regardless of methylation status. PMID:25558448

  1. Survival improvement in anaplastic astrocytoma, combining external radiation with halogenated pyrimidines: final report of RTOG 86-12, phase I-II study

    International Nuclear Information System (INIS)

    Purpose: This study evaluated the toxicity and tumor efficacy of the halopyrimidine IUdR as a chemical modifier of radiation response in patients with malignant glioma. The preliminary results published in 1993 demonstrated no real advantage in the group of patients with glioblastoma. However, a benefit appeared to be evolving in the group of patients with Anaplastic Astrocytoma (AA). We are now presenting the results on the long-term follow-up of patients with AA. Methods and Materials: Between August 1987 and October 1991, 79 patients were entered in a prospective study with newly diagnosed malignant glioma. Twenty-one of 79 were AA. The study was designed to have a fixed dose of radiation consisting of 60.16 Gy in 32 fractions in 6.5 weeks but varying the dose schedule of IUdR, delivered in a continuous intravenous infusion of long (96 h) or short (48 and 24 h) duration, every week for the 6.5 weeks of radiation treatment. Results: The last AA patient was entered in March 1991. Ninety-five percent of the AA patients were under 59 years of age and 86% had a Karnofsky score 80. Thirty-eight percent had a tumor diameter of less than 5 cm and 52% had a tumor diameter between 5-10 cm. Seventy-six percent had partial or total tumor resection. The toxicity of this treatment was acceptable and has already been published elsewhere. At the time of this report, 14 out of 21 patients with AA are dead. The median survival, calculated from the Kaplan-Meier, is 3.2 years. Thirty-three percent of the patients have survived 5 years. These results compare favorably with the best results reported in the literature with postoperative external radiation plus chemotherapy, median survival time (MST) of 3 years, and previous Radiation Therapy Oncology Group (RTOG) experience with radiation alone, MST of 2 years. Conclusions: Our findings in patients with AA corroborate the improved therapeutic results published recently when combining external radiation with 'long' infusion of i

  2. A novel dendritic nanocarrier of polyamidoamine-polyethylene glycol-cyclic RGD for “smart” small interfering RNA delivery and in vitro antitumor effects by human ether-à-go-go-related gene silencing in anaplastic thyroid carcinoma cells

    Directory of Open Access Journals (Sweden)

    Li G

    2013-03-01

    Full Text Available Guanhua Li,1,2 Zuojun Hu,1 Henghui Yin,1 Yunjian Zhang,1 Xueling Huang,1 Shenming Wang,1 Wen Li2 1Department of Vascular and Thyroid Surgery, 2Key Laboratory of Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China Abstract: The application of RNA interference techniques is promising in gene therapeutic approaches, especially for cancers. To improve safety and efficiency of small interfering RNA (siRNA delivery, a triblock dendritic nanocarrier, polyamidoamine-polyethylene glycol-cyclic RGD (PAMAM-PEG-cRGD, was developed and studied as an siRNA vector targeting the human ether-à-go-go-related gene (hERG in human anaplastic thyroid carcinoma cells. Structure characterization, particle size, zeta potential, and gel retardation assay confirmed that complete triblock components were successfully synthesized with effective binding capacity of siRNA in this triblock nanocarrier. Cytotoxicity data indicated that conjugation of PEG significantly alleviated cytotoxicity when compared with unmodified PAMAM. PAMAM-PEG-cRGD exerted potent siRNA cellular internalization in which transfection efficiency measured by flow cytometry was up to 68% when the charge ratio (N/P ratio was 3.5. Ligand-receptor affinity together with electrostatic interaction should be involved in the nano-siRNA endocytosis mechanism and we then proved that attachment of cRGD enhanced cellular uptake via RGD-integrin recognition. Gene silencing was evaluated by reverse transcription polymerase chain reaction and PAMAM-PEG-cRGD-siRNA complex downregulated the expression of hERG to 26.3% of the control value. Furthermore, gene knockdown of hERG elicited growth suppression as well as activated apoptosis by means of abolishing vascular endothelial growth factor secretion and triggering caspase-3 cascade in anaplastic thyroid carcinoma cells. Our study demonstrates that this novel triblock polymer, PAMAM-PEG-cRGD, exhibits negligible

  3. 18F-FDG PET/CT-Negative Recurrent High-Grade Anaplastic Astrocytoma Detected by 18F-FDOPA PET-CT

    International Nuclear Information System (INIS)

    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 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET-CT), as the initial primary tumour was high grade in nature. 18F-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-6-18F-fluoro-L-phenylalanine (18F-FDOPA) PET-CT was done, 5 days after 18F-FDG PET-CT. The study revealed an 18F-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. 18F-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. 18F-FDG uptake correlates with tumour grade, with high-grade gliomas (grades III and IV) showing higher uptake than low-grade gliomas. Therefore, in spite of its

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-12-15

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

  5. Thrombospondin-1 Silencing Down-Regulates Integrin Expression Levels in Human Anaplastic Thyroid Cancer Cells with BRAFV600E: New Insights in the Host Tissue Adaptation and Homeostasis of Tumor Microenvironment

    Science.gov (United States)

    Duquette, Mark; Sadow, Peter M.; Lawler, Jack; Nucera, Carmelo

    2013-01-01

    Background and Rationale: Anaplastic thyroid cancer (ATC) is characterized by pleomorphic cells, has a poor prognosis, is highly devastating disease, and is not curable. No reliable biomarkers of metastatic potential, helpful for early diagnosis of ATC and therapeutic response have been found yet. Thrombospondin-1 (TSP-1) plays a fundamental role in cancer progression by regulating cell stromal cross-talk in the tumor microenvironment. Goals: Our goal was to understand whether TSP-1 could affect protein levels of its integrin receptors (e.g., ITGα3, α6, and β1) and cell morphology in BRAFV600E-ATC cells in vitro and in vivo. Experimental Design: Anaplastic thyroid cancer-derived cell cultures and western blotting were used to assess integrin protein expression upon TSP-1 silencing. Immunohistochemistry was performed on orthotopic primary human ATC and metastatic ATC in lung tissue to compare TSP-1 and integrin protein expression levels. Results: TSP-1 knock-down down-regulates ITGα3, α6, and β1 in BRAFV600E-human ATC cells. BRAFV600E-ATC cells with TSP-1 knock-down were rounded compared to control cells, which displayed a spread morphology. TSP-1 knock-down also reduced TSP-1, ITGα3, α6, and β1 protein expression levels in vivo in the ATC microenvironment, which is enriched in stromal and inflammatory cells. Conclusion: TSP-1 silencing causes changes in ITG levels and ATC cell morphology. The assessment of TSP-1 and ITG levels might contribute to earlier metastatic potential of BRAFV600E-positive aggressive thyroid cancers, and allow improved patient selection for clinical trials. PMID:24348463

  6. A phase 3 randomized study of radiotherapy plus procarbazine, CCNU, and vincristine (PCV) with or without BUdR for the treatment of anaplastic astrocytoma: a preliminary report of RTOG 9404

    International Nuclear Information System (INIS)

    Purpose: This study was an open label, randomized Phase 3 trial in newly diagnosed patients with anaplastic glioma comparing radiotherapy plus adjuvant procarbazine, CCNU, and vincristine (PCV) chemotherapy with or without bromodeoxyuridine (BUdR) given as a 96-hour infusion each week of radiotherapy. Methods and Materials: Only patients 18 years or older with newly diagnosed anaplastic glioma were eligible; central pathology review was accomplished, but was not mandated prior to registration. The study had initially opened as a Northern California Oncology Group (NCOG) trial in 1991, becoming an Intergroup RTOG, SWOG, and NCCTG study in July 1994. Total accrual of 293 patients was planned as the sample size, using survival and time to tumor progression as the primary endpoints. The experiment arm (RT/BUdR plus PCV) was to be compared to the control arm (RT plus PCV) using an alpha = 0.05, one-tailed, with a power of 85% for detecting an increase in median survival from 160 to 240 weeks, assuming a 3-year follow-up after completion of enrollment. Results: As of July 1996, 281 patients had been randomized; 53 (20%) were ineligible, primarily based upon central pathology review, and another 39 cases were canceled. In total, 30% of cases were excluded from analysis. The treatment arms were well balanced despite this rate of exclusion. The RTOG Data Monitoring Committee recommended suspension of enrollment in July 1996 based upon a stochastic curtailment analysis which strongly suggested that the addition of BUdR would not be associated with increased survival. In February 1997, the study was closed prior to full enrollment. At that time, the 1-year survival estimates were 82% versus 68% for RT plus PCV and RT/BUdR plus PCV respectively (one-sided, p = 0.96). The conditional power analysis indicated that even with an additional 12 months of additional accrual and follow-up the probability of detecting the prespecified difference was less than 0.01%. The differences in

  7. 儿童间变型大细胞非霍奇金淋巴瘤临床特点及疗效分析%Clinical features and therapeutic evaluation in children with anaplastic large cell non-Hodgkin's lymphoma

    Institute of Scientific and Technical Information of China (English)

    梁爱斌; 谢晓恬; 石苇; 邵越霞; 刘兴元; 傅晓燕; 王耀平

    2001-01-01

    为探讨儿童间变型大细胞非霍奇金淋巴瘤(CALCL)临床特点、方案选择及疗效分析,对4例儿童间变型大细胞性非霍奇金淋巴瘤患儿进行临床诊断、免疫分型、治疗、随访及疗效总结。结果:4例CALCL患儿中,CD30+3例,T细胞型3例,B细胞型1例;部分缓解1例,完全缓解3例,其中1例CR 7月后脑膜复发。结论:间变型大细胞淋巴瘤(ALCL)为非霍奇金淋巴瘤的一种特殊类型,临床表现多样,与其他恶性淋巴瘤相比恶性程度稍低,较少累及骨髓,预后较好,但与免疫分型及临床分期密切相关。

  8. Redifferentiation and induction of tumor suppressors miR-122 and miR-375 by the PAX8/PPARγ fusion protein inhibits anaplastic thyroid cancer: a novel therapeutic strategy.

    Science.gov (United States)

    Reddi, H V; Driscoll, C B; Madde, P; Milosevic, D; Hurley, R M; McDonough, S J; Hallanger-Johnson, J; McIver, B; Eberhardt, N L

    2013-05-01

    Anaplastic thyroid cancer (ATC) is an aggressive, fatal disease unresponsive to traditional therapies, generating a need to develop effective therapies. The PAX8/PPARγ fusion protein (PPFP) has been shown to favorably modulate tumor growth in follicular thyroid cancer, prompting our evaluation of its efficacy to inhibit ATC cell and tumor growth in vitro and in vivo. PPFP was constitutively expressed in five ATC cell lines: BHT-101, FRO, C-643, KTC-2 and KTC-3, and inhibited cell growth in four of five cell lines and xenograft tumor growth in four of four cell lines. PPFP-mediated growth inhibition involved multiple mechanisms, including upregulation of miR-122 and miR-375, associated with decreased angiogenesis and AKT pathway inactivation, respectively. Also, PPFP expression resulted in marked increase of thyroid-specific marker transcripts, including PAX8, thyroid peroxidase (TPO), sodium iodide symporter (NIS) and thyroglobulin, to varying degrees by activating their respective promoters, suggesting that PPFP induced cellular redifferentiation. Functional studies demonstrate that increased NIS messenger RNA is not associated with increased 125I uptake. However, ectopic expression of wild-type NIS-induced perchlorate-sensitive iodine uptake, suggesting that endogenous NIS in ATC cell lines is defective. As current treatment for ATC is only palliative, overexpression of PPFP may offer a novel therapeutic strategy for the treatment of ATC. PMID:23598436

  9. Role of Evaluating MGMT Status and 1p36 Deletion in Radiosurgery-Induced Anaplastic Ependymoma That Rapidly and Completely Resolved by Temozolomide Alone: Case Report and Review of the Literature.

    Science.gov (United States)

    Hirono, Seiichiro; Iwadate, Yasuo; Kambe, Michiyo; Hiwasa, Takaki; Takiguchi, Masaki; Nakatani, Yukio; Saeki, Naokatsu

    2015-07-01

    Stereotactic gamma knife surgery (GKS)-induced brain tumors are extremely rare, and no ependymal tumors induced by GKS have been reported. Therefore, little is known about their clinical, pathologic, and genetic features. In addition, a regimen of adjuvant chemotherapy for anaplastic ependymoma (AE) has not been established. A 77-year-old man presented with a gait disturbance and left-side cerebellar ataxia more than 19 years after GKS performed for a cerebellar arteriovenous malformation. Imaging studies demonstrated an enhancing mass in the irradiated field with signs of intraventricular dissemination. Surgical resection confirmed the diagnosis of AE. Temozolomide (TMZ) was administrated postoperatively because the methylated promoter region of O(6)-methylguanine-DNA methyltransferase (MGMT) and 1p36 deletion were observed. Surprisingly, images 16 days after TMZ initiation demonstrated a complete resolution of the residual tumor that was maintained after three cycles of TMZ. This first case report of GKS-induced AE emphasizes the importance of genetic evaluation of MGMT and chromosomal deletion of 1p36 that are not commonly performed in primary ependymal tumors. In addition, it is speculated that a GKS-induced tumor may have a different genetic background compared with the primary tumor because the pathogenesis of the tumors differed. PMID:26251808

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

    Science.gov (United States)

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

    2016-03-01

    Adding temozolomide (TMZ) to radiation for patients with newly-diagnosed anaplastic astrocytomas (AAs) is common clinical practice despite the lack of prospective studies demonstrating a survival advantage. Two retrospective studies, each with methodologic limitations, provide conflicting advice regarding treatment. This single-institution retrospective study was conducted to determine survival trends in patients with AA. All patients ≥18 years with newly-diagnosed AA treated at Johns Hopkins from 1995 to 2012 were included. As we incorporated TMZ into high-grade glioma treatment regimens in 2004, patients were divided into pre-2004 and post-2004 groups for analysis. Clinical, radiographic, and pathologic data were collected. Median overall survival (OS) was calculated using Kaplan-Meier estimates. A total of 196 patients were identified; 74 pre-2004 and 122 post-2004; mean age 47 ± 15 years; 57 % male; 87 % white, 69 % surgical debulking. Mean RT dose 5676 + 746 cGy; duration of concurrent chemoradiation 5.8 ± 0.8 weeks; and mean adjuvant chemotherapy 4.3 + 2.8 cycles. Baseline prognostic factors did not differ between groups. Chemotherapy was administered to 12 % of patients pre-2004 (TMZ = 1, procarbazine, lomustine and vincristine = 2, carmustine wafer = 6) and 94 % post-2004 (TMZ in all, p HR 0.75, 0.53-1.06, p = 0.11). Multivariate analysis controlling for age, Karnofsky performance status, and extent of resection revealed a 36 % reduced risk of death (HR 0.64, 0.44-0.91, p = 0.015) in patients treated post-2004. This retrospective review found survival in newly diagnosed patients with AA improved with the addition of temozolomide to standard radiation. Until prospective randomized phase III data are available, these data support the practice of incorporating TMZ in the management of newly-diagnosed AA. PMID:26729269

  11. Diffuse anaplastic leptomeningeal oligodendrogliomatosis mimicking neurosarcoidosis

    OpenAIRE

    Leep Hunderfund, Andrea N.; Zabad, Rana K.; Aksamit, Allen J.; Morris, Jonathan M; Meyer, Fredric B.; Thorell, William E.; Parisi, Joseph E.; Giannini, Caterina

    2013-01-01

    Diffuse leptomeningeal oligodendrogliomatosis is a rare, frequently fatal CNS malignancy that most often affects children.1 Although potentially treatable with chemotherapy and radiation, the radiologic findings are nonspecific and pathologic confirmation of the diagnosis is difficult. We describe an adult patient whose initial presentation mimicked neurosarcoidosis. Despite extensive imaging abnormalities, 3 biopsies were required before the diagnosis of diffuse leptomeningeal oligodendrogli...

  12. Intracranial metastasis of spinal intramedullary anaplastic astrocytoma

    OpenAIRE

    Kataria, Rashim; Bhasme, Vishal; Chopra, Sanjeev; V D Sinha; Singhvi, Shashi

    2011-01-01

    Meningeal spread of spinal intramedullary astrocytoma into the cranium is rare. Only few case reports are available so far in the literature. We report a case of intramedullary high grade astrocytoma of the conus, developing intracranial metastasis after three months of partial excision of the spinal mass. The need for radical surgery, entire neuroaxis radiation, and adjuvant chemotherapy is suggested in the management of malignant spinal cord astrocytoma to prevent dissemination.

  13. Large bowel resection - slideshow

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/presentations/100089.htm Large bowel resection - Series To use the sharing features ... 6 out of 6 Normal anatomy Overview The large bowel [large intestine or the colon] is part ...

  14. Large bowel resection - discharge

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000151.htm Large bowel resection - discharge To use the sharing features ... surgery to remove all or part of your large intestine (large bowel). You may also have had ...

  15. Small & Large Intestine

    Science.gov (United States)

    ... the large intestine produces no digestive enzymes. Chemical digestion is completed in the small intestine before the chyme reaches the large intestine. Functions of the large intestine include the absorption of water and electrolytes and the elimination of ...

  16. Large Neighborhood Search

    DEFF Research Database (Denmark)

    Pisinger, David; Røpke, Stefan

    2010-01-01

    Heuristics based on large neighborhood search have recently shown outstanding results in solving various transportation and scheduling problems. Large neighborhood search methods explore a complex neighborhood by use of heuristics. Using large neighborhoods makes it possible to find better...... candidate solutions in each iteration and hence traverse a more promising search path. Starting from the large neighborhood search method,we give an overview of very large scale neighborhood search methods and discuss recent variants and extensions like variable depth search and adaptive large neighborhood...... search....

  17. Large Pelagics Intercept Survey

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Large Pelagics Intercept Survey (LPIS) is a dockside survey of private and charterboat captains who have just completed fishing trips directed at large pelagic...

  18. Large intestine (colon) (image)

    Science.gov (United States)

    The large intestine is the portion of the digestive system most responsible for absorption of water from the indigestible ... the ileum (small intestine) passes material into the large intestine at the cecum. Material passes through the ...

  19. Large bowel resection

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002941.htm Large bowel resection To use the sharing features on this page, please enable JavaScript. Large bowel resection is surgery to remove all or ...

  20. Fontanelles - excessively large

    Science.gov (United States)

    ... to Expect at Your Office Visit An enlarged large fontanelle is almost always found by the health ... head may be done. Alternative Names Soft spot - large; Newborn care - enlarged fontanelle; Neonatal care - enlarged fontanelle ...

  1. Large myelomeningocele repair

    OpenAIRE

    Farideh Nejat; Nima Baradaran; Mostafa El Khashab

    2011-01-01

    Background: Wound closure is accomplished in most cases of myelomeningocele (MMC) by undermining of the skin edges surrounding the defect. However, large defects cannot be closed reliably by this simple technique. Due to the technical challenge associated with large MMC, surgeons have devised different methods for repairing large defects. In this paper, we report our experience of managing large defects, which we believe bears a direct relationship to decrease the incidence of wound complicat...

  2. ERP inside Large Organizations

    OpenAIRE

    Constantin Daniel AVRAM

    2010-01-01

    Many large companies in Romania are still functioning without an ERP system. Instead they are using traditional application systems built around the strong boundaries of specific functions: finance, selling, HR, production. An ERP will offer lots of advantages among which the integration of functionalities and support for top management decisions. Although the total cost of ownership is not small and there are some risks when implementing an ERP inside large and very large organizations, havi...

  3. Adaptive Large Neighbourhood Search

    DEFF Research Database (Denmark)

    Røpke, Stefan

    Large neighborhood search is a metaheuristic that has gained popularity in recent years. The heuristic repeatedly moves from solution to solution by first partially destroying the solution and then repairing it. The best solution observed during this search is presented as the final solution. This...... tutorial introduces the large neighborhood search metaheuristic and the variant adaptive large neighborhood search that dynamically tunes parameters of the heuristic while it is running. Both heuristics belong to a broader class of heuristics that are searching a solution space using very large...... neighborhoods. The tutorial also present applications of the adaptive large neighborhood search, mostly related to vehicle routing problems for which the heuristic has been extremely successful. We discuss how the heuristic can be parallelized and thereby take advantage of modern desktop computers that...

  4. ERP inside Large Organizations

    Directory of Open Access Journals (Sweden)

    Constantin Daniel AVRAM

    2010-01-01

    Full Text Available Many large companies in Romania are still functioning without an ERP system. Instead they are using traditional application systems built around the strong boundaries of specific functions: finance, selling, HR, production. An ERP will offer lots of advantages among which the integration of functionalities and support for top management decisions. Although the total cost of ownership is not small and there are some risks when implementing an ERP inside large and very large organizations, having such a system is mandatory. Choosing the right product and vendor and using a correct risk management strategy, will ensure a successful implementation.

  5. Large domain graphene

    OpenAIRE

    Li, Xuesong; Magnuson, Carl W.; Venugopal, Archana; Vogel, Eric M.; Rodney S. Ruoff; Colombo, Luigi

    2010-01-01

    Graphene growth by chemical vapor deposition has received a lot of attention recently owing to the ease with which large area films can be grown, but growth of large domain or equivalently large grain size has not been reported yet. In this brevia, we report on a CVD process that yields graphene with domains of hundreds of micrometers, by very low pressure CVD, less than 50 mTorr, and very low precursor flow rates using methane as the source of carbon on the inside of copper foil enclosures a...

  6. Large whale incident database

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Large whale stranding, death, ship strike and entanglement incidents are all recorded to monitor the health of each population and track anthropogenic factors that...

  7. Large Customers (DR Sellers)

    Energy Technology Data Exchange (ETDEWEB)

    Kiliccot, Sila [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2011-10-25

    State of the large customers for demand response integration of solar and wind into electric grid; openADR; CAISO; DR as a pseudo generation; commercial and industrial DR strategies; California regulations

  8. Large Pelagics Biological Survey

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Large Pelagics Biological Survey (LPBS) collects additional length and weight information and body parts such as otoliths, caudal vertebrae, dorsal spines, and...

  9. Very large graphs

    OpenAIRE

    Lovasz, Laszlo

    2009-01-01

    In the last decade it became apparent that a large number of the most interesting structures and phenomena of the world can be described by networks: separable elements, with connections (or interactions) between certain pairs of them. These huge networks pose exciting challenges for the mathematician. Graph Theory (the mathematical theory of networks) faces novel, unconventional problems: these very large networks (like the Internet) are never completely known, in most cases they are not eve...

  10. Large electrostatic accelerators

    Energy Technology Data Exchange (ETDEWEB)

    Jones, C.M.

    1984-01-01

    The increasing importance of energetic heavy ion beams in the study of atomic physics, nuclear physics, and materials science has partially or wholly motivated the construction of a new generation of large electrostatic accelerators designed to operate at terminal potentials of 20 MV or above. In this paper, the author briefly discusses the status of these new accelerators and also discusses several recent technological advances which may be expected to further improve their performance. The paper is divided into four parts: (1) a discussion of the motivation for the construction of large electrostatic accelerators, (2) a description and discussion of several large electrostatic accelerators which have been recently completed or are under construction, (3) a description of several recent innovations which may be expected to improve the performance of large electrostatic accelerators in the future, and (4) a description of an innovative new large electrostatic accelerator whose construction is scheduled to begin next year. Due to time and space constraints, discussion is restricted to consideration of only tandem accelerators.

  11. LARGE SCALE GLAZED

    DEFF Research Database (Denmark)

    Bache, Anja Margrethe

    2010-01-01

    WORLD FAMOUS ARCHITECTS CHALLENGE TODAY THE EXPOSURE OF CONCRETE IN THEIR ARCHITECTURE. IT IS MY HOPE TO BE ABLE TO COMPLEMENT THESE. I TRY TO DEVELOP NEW AESTHETIC POTENTIALS FOR THE CONCRETE AND CERAMICS, IN LARGE SCALES THAT HAS NOT BEEN SEEN BEFORE IN THE CERAMIC AREA. IT IS EXPECTED TO RESULT...... IN NEW TYPES OF LARGE SCALE AND VERY THIN, GLAZED CONCRETE FAÇADES IN BUILDING. IF SUCH ARE INTRODUCED IN AN ARCHITECTURAL CONTEXT THEY WILL HAVE A DISTINCTIVE IMPACT ON THE VISUAL EXPRESSION OF THE BUILDING. THE QUESTION IS WHAT KIND. THAT I WILL ATTEMPT TO ANSWER IN THIS ARTICLE THROUGH OBSERVATION...... OF SELECTED EXISTING BUILDINGS IN AND AROUND COPENHAGEN COVERED WITH MOSAIC TILES, UNGLAZED OR GLAZED CLAY TILES. ITS BUILDINGS WHICH HAVE QUALITIES THAT I WOULD LIKE APPLIED, PERHAPS TRANSFORMED OR MOST PREFERABLY, INTERPRETED ANEW, FOR THE LARGE GLAZED CONCRETE PANELS I AM DEVELOPING. KEYWORDS...

  12. Large-Scale Disasters

    Science.gov (United States)

    Gad-El-Hak, Mohamed

    "Extreme" events - including climatic events, such as hurricanes, tornadoes, and drought - can cause massive disruption to society, including large death tolls and property damage in the billions of dollars. Events in recent years have shown the importance of being prepared and that countries need to work together to help alleviate the resulting pain and suffering. This volume presents a review of the broad research field of large-scale disasters. It establishes a common framework for predicting, controlling and managing both manmade and natural disasters. There is a particular focus on events caused by weather and climate change. Other topics include air pollution, tsunamis, disaster modeling, the use of remote sensing and the logistics of disaster management. It will appeal to scientists, engineers, first responders and health-care professionals, in addition to graduate students and researchers who have an interest in the prediction, prevention or mitigation of large-scale disasters.

  13. Large litter sizes

    DEFF Research Database (Denmark)

    Sandøe, Peter; Rutherford, K.M.D.; Berg, Peer

    2012-01-01

    This paper presents some key results and conclusions from a review (Rutherford et al. 2011) undertaken regarding the ethical and welfare implications of breeding for large litter size in the domestic pig and about different ways of dealing with these implications. Focus is primarily on the direct...... adverse consequences for animal welfare of Danish breeding for large litter sizes due to increased piglet mortality and the subsequent attempts to reverse these consequences by breeding for number of live piglets at day five rather than number of piglets born. By this change of breeding goal it seems...

  14. Large gauged Q balls

    Science.gov (United States)

    Anagnostopoulos, K. N.; Axenides, M.; Floratos, E. G.; Tetradis, N.

    2001-12-01

    We study Q balls associated with local U(1) symmetries. Such Q balls are expected to become unstable for large values of their charge because of the repulsion mediated by the gauge force. We consider the possibility that the repulsion is eliminated through the presence in the interior of the Q ball of fermions with charge opposite to that of the scalar condensate. Another possibility is that two scalar condensates of opposite charge form in the interior. We demonstrate that both these scenarios can lead to the existence of classically stable, large, gauged Q balls. We present numerical solutions, as well as an analytical treatment of the ``thin-wall'' limit.

  15. Large electromagnetic pumps. [LMFBR

    Energy Technology Data Exchange (ETDEWEB)

    Kilman, G.B.

    1976-01-01

    The development of large electromagnetic pumps for the liquid metal heat transfer systems of fission reactors has progressed for a number of years. Such pumps are now planned for fusion reactors and solar plants as well. The Einstein-Szilard (annular) pump has been selected as the preferred configuration. Some of the reasons that electromagnetic pumps may be preferred over mechanical pumps and why the annular configuration was selected are discussed. A detailed electromagnetic analysis of the annular pump, based on slug flow, is presented. The analysis is then used to explore the implications of large size and power on considerations of electromagnetic skin effect, geometric skin effect and the cylindrical geometry.

  16. Developing Large Web Applications

    CERN Document Server

    Loudon, Kyle

    2010-01-01

    How do you create a mission-critical site that provides exceptional performance while remaining flexible, adaptable, and reliable 24/7? Written by the manager of a UI group at Yahoo!, Developing Large Web Applications offers practical steps for building rock-solid applications that remain effective even as you add features, functions, and users. You'll learn how to develop large web applications with the extreme precision required for other types of software. Avoid common coding and maintenance headaches as small websites add more pages, more code, and more programmersGet comprehensive soluti

  17. The large hadron computer

    CERN Multimedia

    Hirstius, Andreas

    2008-01-01

    Plans for dealing with the torrent of data from the Large Hadron Collider's detectors have made the CERN particle-phycis lab, yet again, a pioneer in computing as well as physics. The author describes the challenges of processing and storing data in the age of petabyt science. (4 pages)

  18. Teaching Large Evening Classes

    Science.gov (United States)

    Wambuguh, Oscar

    2008-01-01

    High enrollments, conflicting student work schedules, and the sheer convenience of once-a-week classes are pushing many colleges to schedule evening courses. Held from 6 to 9 pm or 7 to 10 pm, these classes are typically packed, sometimes with more than 150 students in a large lecture theater. How can faculty effectively teach, control, or even…

  19. Teaching Very Large Classes

    Science.gov (United States)

    DeRogatis, Amy; Honerkamp, Kenneth; McDaniel, Justin; Medine, Carolyn; Nyitray, Vivian-Lee; Pearson, Thomas

    2014-01-01

    The editor of "Teaching Theology and Religion" facilitated this reflective conversation with five teachers who have extensive experience and success teaching extremely large classes (150 students or more). In the course of the conversation these professors exchange and analyze the effectiveness of several active learning strategies they…

  20. Large N Cosmology

    Science.gov (United States)

    Hawking, S. W.

    2001-09-01

    The large N approximation should hold in cosmology even at the origin of the universe. I use ADS-CFT to calculate the effective action and obtain a cosmological model in which inflation is driven by the trace anomaly. Despite having ghosts, this model can agree with observations.

  1. Estimating Large Numbers

    Science.gov (United States)

    Landy, David; Silbert, Noah; Goldin, Aleah

    2013-01-01

    Despite their importance in public discourse, numbers in the range of 1 million to 1 trillion are notoriously difficult to understand. We examine magnitude estimation by adult Americans when placing large numbers on a number line and when qualitatively evaluating descriptions of imaginary geopolitical scenarios. Prior theoretical conceptions…

  2. Large superconducting magnets

    CERN Document Server

    Pérot, J

    1981-01-01

    Discusses the use of large superconducting magnets in the areas of particle physics, thermonuclear fusion, and magnetohydrodynamics. In addition to considering the physics of the superconducting state, the article considers machines such as BEBC (Big European Bubble Chamber) at CERN, the LINAC at SLAC and possible Tokamak applications. The future application of superconductors to high speed trains is discussed. (0 refs).

  3. LARGE SCALE GLAZED

    DEFF Research Database (Denmark)

    Bache, Anja Margrethe

    WORLD FAMOUS ARCHITECTS CHALLENGE TODAY THE EXPOSURE OF CONCRETE IN THEIR ARCHITECTURE. IT IS MY HOPE TO BE ABLE TO COMPLEMENT THESE. I TRY TO DEVELOP NEW AESTHETIC POTENTIALS FOR THE CONCRETE AND CERAMICS, IN LARGE SCALES THAT HAS NOT BEEN SEEN BEFORE IN THE CERAMIC AREA. IT IS EXPECTED TO RESUL......: COLOR, LIGHT AND TEXTURE, GLAZED AND UNGLAZED, BUILDING FACADES...

  4. Large Hadron Collider

    CERN Multimedia

    2007-01-01

    "In the spring 2008, the Large Hadron Collider (LHC) machine at CERN (the European Particle Physics laboratory) will be switched on for the first time. The huge machine is housed in a circular tunnel, 27 km long, excavated deep under the French-Swiss border near Geneva." (1,5 page)

  5. Large myelomeningocele repair

    Directory of Open Access Journals (Sweden)

    Farideh Nejat

    2011-01-01

    Full Text Available Background: Wound closure is accomplished in most cases of myelomeningocele (MMC by undermining of the skin edges surrounding the defect. However, large defects cannot be closed reliably by this simple technique. Due to the technical challenge associated with large MMC, surgeons have devised different methods for repairing large defects. In this paper, we report our experience of managing large defects, which we believe bears a direct relationship to decrease the incidence of wound complications. Materials and Methods: Forty children with large MMCs underwent surgical repair and represent our experience. We recommend using all hairy skin around the defect as a way to decrease the tension on the edges of the wound and the possible subsequent necrosis. It is our experience that vertical incision on one or two flanks parallel to the midline can decrease the tension of the wound. Moreover, ventriculo-peritoneal shunting for children who developed hydrocephalus was performed simultaneously, which constitutes another recommendation for preventing fluid collection and build up of pressure on the wound. Results: Patients in this study were in the age range of 2 days to 8 years. The most common location of MMC was in the thoracolumbar area. All but four patients had severe weakness in lower extremities. We used as much hairy skin around the MMC sac as possible in all cases. Vertical incisions on one or both flanks and simultaneous shunt procedure were performed in 36 patients. We treated children with large MMC defects with acceptable tension-free closure. Nonetheless, three patients developed superficial skin infection and partial wound dehiscence, and they were managed conservatively. Conclusions: We recommend using all hairy skin around the MMC defect for closure of large defects. In cases that were expected to be at a higher risk to develop dehiscence release incisions on one or two flanks towards the fascia were found to be useful. Simultaneous

  6. The Large Hadron Collider

    CERN Document Server

    Evans, Lyndon

    2012-01-01

    The construction of the Large Hadron Collider (LHC) has been a massive endeavour spanning almost 30 years from conception to commissioning. Building the machine with the highest possible energy (7 TeV) in the existing large electron–positron (LEP) collider tunnel of 27 km circumference and with a tunnel diameter of only 3.8 m has required considerable innovation. The first was the development of a two-in-one magnet, where the two rings are integrated into a single magnetic structure. This compact two-in-one structure was essential for the LHC owing to the limited space available in the existing LEP collider tunnel and the cost. The second was a bold move to the use of superfluid helium cooling on a massive scale, which was imposed by the need to achieve a high (8.3 T) magnetic field using an affordable Nb-Ti superconductor.

  7. Large Curved Surface Measurement

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The measurement principle of large curved surface through theodolite industry survey system is introduced. Two methods are suggested with respect to the distribution range of curved surface error. The experiments show that the measurement precision can be up to 0.15mm with relative precision of 3×10-5. Finally, something needed paying attention to and the application aspects on theodolite industry survey system are given.

  8. India: Large and Small

    OpenAIRE

    Amartya Sen

    2007-01-01

    The past and present of India can be seen in many different perspectives. There is a case for focusing particularly on the long history of the argumentative tradition in India, and its continuing relevance today. The intellectual largeness of India links closely with the reach of our argumentative tradition. There are lots of economic and political issues which needs urgent attention. [Lecture at India Habitat Centre, New Delhi].

  9. Buyouts in Large Companies

    OpenAIRE

    Hermalin, Benjamin; SCHWARTZ, Alan

    1998-01-01

    We consider legal rules that determine the price at which minority shareholders can be excluded from the corporate enterprise after a change in control. These rules affect investment after such a change, as well as probability of the change itself. Our principal results are that minority shareholders should be given the value that their interest would have had were no later investment made and that this rule is best implemented in large companies by awarding the minority the preinvestment mar...

  10. The Large Hadron Collider

    CERN Document Server

    Juettner Fernandes, Bonnie

    2014-01-01

    What really happened during the Big Bang? Why did matter form? Why do particles have mass? To answer these questions, scientists and engineers have worked together to build the largest and most powerful particle accelerator in the world: the Large Hadron Collider. Includes glossary, websites, and bibliography for further reading. Perfect for STEM connections. Aligns to the Common Core State Standards for Language Arts. Teachers' Notes available online.

  11. Large joints in graphs

    CERN Document Server

    Bollobas, Bela

    2010-01-01

    We show that if G is a graph of sufficiently large order n containing as many r-cliques as the r-partite Turan graph of order n; then for some C>0 G has more than Cn^(r-1) (r+1)-cliques sharing a common edge unless G is isomorphic to the the r-partite Turan graph of order n. This structural result generalizes a previous result that has been useful in extremal graph theory.

  12. Large N_c

    OpenAIRE

    Jenkins, Elizabeth E.

    2009-01-01

    The 1/N_c expansion of QCD with N_c=3 has been successful in explaining a wide variety of QCD phenomenology. Here I focus on the contracted spin-flavor symmetry of baryons in the large-N_c limit and deviations from spin-flavor symmetry due to corrections suppressed by powers of 1/N_c. Baryon masses provide an important example of the 1/N_c expansion, and successful predictions of masses of heavy-quark baryons continue to be tested by experiment. The ground state charmed baryon masses have all...

  13. Large Particle Titanate Sorbents

    Energy Technology Data Exchange (ETDEWEB)

    Taylor-Pashow, K. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

    2015-10-08

    This research project was aimed at developing a synthesis technique for producing large particle size monosodium titanate (MST) to benefit high level waste (HLW) processing at the Savannah River Site (SRS). Two applications were targeted, first increasing the size of the powdered MST used in batch contact processing to improve the filtration performance of the material, and second preparing a form of MST suitable for deployment in a column configuration. Increasing the particle size should lead to improvements in filtration flux, and decreased frequency of filter cleaning leading to improved throughput. Deployment of MST in a column configuration would allow for movement from a batch process to a more continuous process. Modifications to the typical MST synthesis led to an increase in the average particle size. Filtration testing on dead-end filters showed improved filtration rates with the larger particle material; however, no improvement in filtration rate was realized on a crossflow filter. In order to produce materials suitable for column deployment several approaches were examined. First, attempts were made to coat zirconium oxide microspheres (196 µm) with a layer of MST. This proved largely unsuccessful. An alternate approach was then taken synthesizing a porous monolith of MST which could be used as a column. Several parameters were tested, and conditions were found that were able to produce a continuous structure versus an agglomeration of particles. This monolith material showed Sr uptake comparable to that of previously evaluated samples of engineered MST in batch contact testing.

  14. Large Superconducting Magnet Systems

    CERN Document Server

    Védrine, P

    2014-01-01

    The increase of energy in accelerators over the past decades has led to the design of superconducting magnets for both accelerators and the associated detectors. The use of Nb−Ti superconducting materials allows an increase in the dipole field by up to 10 T compared with the maximum field of 2 T in a conventional magnet. The field bending of the particles in the detectors and generated by the magnets can also be increased. New materials, such as Nb3Sn and high temperature superconductor (HTS) conductors, can open the way to higher fields, in the range 13–20 T. The latest generations of fusion machines producing hot plasma also use large superconducting magnet systems.

  15. Large area plasma source

    Science.gov (United States)

    Foster, John (Inventor); Patterson, Michael (Inventor)

    2008-01-01

    An all permanent magnet Electron Cyclotron Resonance, large diameter (e.g., 40 cm) plasma source suitable for ion/plasma processing or electric propulsion, is capable of producing uniform ion current densities at its exit plane at very low power (e.g., below 200 W), and is electrodeless to avoid sputtering or contamination issues. Microwave input power is efficiently coupled with an ionizing gas without using a dielectric microwave window and without developing a throat plasma by providing a ferromagnetic cylindrical chamber wall with a conical end narrowing to an axial entrance hole for microwaves supplied on-axis from an open-ended waveguide. Permanent magnet rings are attached inside the wall with alternating polarities against the wall. An entrance magnet ring surrounding the entrance hole has a ferromagnetic pole piece that extends into the chamber from the entrance hole to a continuing second face that extends radially across an inner pole of the entrance magnet ring.

  16. Large Scale Solar Heating

    DEFF Research Database (Denmark)

    Heller, Alfred

    2001-01-01

    The main objective of the research was to evaluate large-scale solar heating connected to district heating (CSDHP), to build up a simulation tool and to demonstrate the application of the simulation tool for design studies and on a local energy planning case. The evaluation was mainly carried out...... model is designed and validated on the Marstal case. Applying the Danish Reference Year, a design tool is presented. The simulation tool is used for proposals for application of alternative designs, including high-performance solar collector types (trough solar collectors, vaccum pipe collectors......). Simulation programs are proposed as control supporting tool for daily operation and performance prediction of central solar heating plants. Finaly the CSHP technolgy is put into persepctive with respect to alternatives and a short discussion on the barries and breakthrough of the technology are given....

  17. The association of pathological type、IDH-1 mutations and MGMT promoter methylation status on “pseudo-progress” of anaplastic gliomas%病理类型、IDH-1突变和MGMT启动子甲基化状态与间变性胶质瘤假性进展的相关性

    Institute of Scientific and Technical Information of China (English)

    李宏; 陆云涛; 漆松涛; 俞磊; 欧阳辉; 刘亚伟

    2013-01-01

    目的:明确间变性胶质瘤(Anaplastic glioma,AG)组织中病理类型、IDH-1基因突变以及MGMT启动子甲基化与患者综合治疗后发生假性进展(Pseudoprogression,PsPD)之间的相互关系.方法:对47例间变性胶质瘤标本采用基因片段测序的方法检测异柠檬酸脱氢酶(IDH-1)突变和MGMT启动子甲基化状态情况.对所有病例进行临床随访,结合肿瘤的病理类型,探讨其对术后PsPD发生的提示作用.结果:47例AG患者中有24例出现早期进展(6个月内).9例PsPD中IDH-1突变和MGMT启动子甲基化分别是6例和7例;另15例真性复发患者IDH-1突变和MGMT启动子甲基化分别是3例和5例,IDH-1突变对PsPD检出率与MGMT启动子甲基化相比,无明显差异(x2<0.02,P>0.9);PsPD中含少突胶质细胞病理成分的4例病例,包括3例间变性少突胶质细胞瘤(AO)和1例间变性少突显形细胞瘤(AOA),全部发生IDH-1突变,另5例间变性显形细胞瘤(AA)中有2例发生IDH-1突变,IDH-1突变对PsPD检出率与病理类型中含少突胶质细胞成分相比,无明显差异(x2=0.5,P>0.5).结论:病理类型中含有少突胶质细胞成分、存在IDH-1突变和MGMT启动子甲基化可以作为间变性胶质瘤中预测PsPD的可靠客观预计指标,有利于鉴别肿瘤PsPD和真性复发.%Aim:To identify the relationship between Pathological type,IDH mutation,MGMT promoter methylation in clinical samples of anaplastic gliomas (AG) with Pseudoprogression (PsPD) in patients received comprehensive treatment.Methods:DNA direct sequencing was used to detect IDH-1 mutation and MGMT promoter methylation status of the 47 clinical samples of AG.Clinical data of all patients with AG treated with surgery followed by radiotherapy plus (or not) concomitant temozolomide (TMZ) were followed up.IDH mutation and MGMT promoter methylation were analyzed statistically combined with pathological type of tumor to identify the predictive role of them on postoperative Ps

  18. Large scale traffic simulations

    Energy Technology Data Exchange (ETDEWEB)

    Nagel, K.; Barrett, C.L. [Los Alamos National Lab., NM (United States)]|[Santa Fe Institute, NM (United States); Rickert, M. [Los Alamos National Lab., NM (United States)]|[Universitaet zu Koeln (Germany)

    1997-04-01

    Large scale microscopic (i.e. vehicle-based) traffic simulations pose high demands on computational speed in at least two application areas: (i) real-time traffic forecasting, and (ii) long-term planning applications (where repeated {open_quotes}looping{close_quotes} between the microsimulation and the simulated planning of individual person`s behavior is necessary). As a rough number, a real-time simulation of an area such as Los Angeles (ca. 1 million travellers) will need a computational speed of much higher than 1 million {open_quotes}particle{close_quotes} (= vehicle) updates per second. This paper reviews how this problem is approached in different projects and how these approaches are dependent both on the specific questions and on the prospective user community. The approaches reach from highly parallel and vectorizable, single-bit implementations on parallel supercomputers for Statistical Physics questions, via more realistic implementations on coupled workstations, to more complicated driving dynamics implemented again on parallel supercomputers. 45 refs., 9 figs., 1 tab.

  19. Large scale tracking algorithms.

    Energy Technology Data Exchange (ETDEWEB)

    Hansen, Ross L.; Love, Joshua Alan; Melgaard, David Kennett; Karelitz, David B.; Pitts, Todd Alan; Zollweg, Joshua David; Anderson, Dylan Z.; Nandy, Prabal; Whitlow, Gary L.; Bender, Daniel A.; Byrne, Raymond Harry

    2015-01-01

    Low signal-to-noise data processing algorithms for improved detection, tracking, discrimination and situational threat assessment are a key research challenge. As sensor technologies progress, the number of pixels will increase signi cantly. This will result in increased resolution, which could improve object discrimination, but unfortunately, will also result in a significant increase in the number of potential targets to track. Many tracking techniques, like multi-hypothesis trackers, suffer from a combinatorial explosion as the number of potential targets increase. As the resolution increases, the phenomenology applied towards detection algorithms also changes. For low resolution sensors, "blob" tracking is the norm. For higher resolution data, additional information may be employed in the detection and classfication steps. The most challenging scenarios are those where the targets cannot be fully resolved, yet must be tracked and distinguished for neighboring closely spaced objects. Tracking vehicles in an urban environment is an example of such a challenging scenario. This report evaluates several potential tracking algorithms for large-scale tracking in an urban environment.

  20. THE LARGE MILLIMETER TELESCOPE

    Directory of Open Access Journals (Sweden)

    D. H. Hughes

    2009-01-01

    Full Text Available This paper, presented on behalf of the Large Millimeter Telescope (LMT project team, describes the status and near-term plans for the telescope and its initial instrumentation. The LMT is a bi-national collaboration between M xico and the USA, led by the Instituto Nacional de Astrof sica, ptica y Electr nica (INAOE and the University of Massachusetts at Amherst, to construct, commission and operate a 50 m diameter millimeterwave radio telescope. Construction activities are nearly complete at the LMT site, at an altitude of 4600 m on the summit of Sierra Negra, an extinct volcano in the Mexican state of Puebla. Full movement of the telescope, under computer control in both azimuth and elevation, has been achieved. First-light at centimeter wavelengths on astronomical sources was obtained in November 2006. Installation of precision surface segments for millimeter-wave operation is underway, with the inner 32 m diameter of the surface now complete and ready to be used to obtain rst-light at millimeter wavelengths in 2008. Installation of the remainder of the re ector will continue during the next year and be completed in 2009 for nal commissioning of the antenna. The full LMT antenna, out ted with its initial complement of scienti c instruments, will be a world-leading scienti c research facility for millimeter-wave astronomy.

  1. A large Cerenkov detector

    International Nuclear Information System (INIS)

    Several problems, e.g. a test of nucleon conservation and high-energy neutrino detection of interest to us at Case Institute, have led to the construction of a large Cerenkov detector. This device consists of a tank 2.4 m in diameter and 2.1 m high which is painted with a white reflecting coat. The 7400-l water-volume used as the filling at present is viewed from above by 52 type-6364 Dumont multiplier phototubes. Internal to the detector as it is being currently used is a 200-l liquid scintillation-counter enclosed in an 8000-kg Fe shield. In this paper we describe constructional details and the response of the detector using cosmic-ray muons as a probe. We also present results on the effectiveness of the detector as an anti-coincidence blanket and will discuss the relevance of these numbers to the question of detecting high-energy neutrinos-both cosmic and man-made. (author)

  2. Applied large eddy simulation.

    Science.gov (United States)

    Tucker, Paul G; Lardeau, Sylvain

    2009-07-28

    Large eddy simulation (LES) is now seen more and more as a viable alternative to current industrial practice, usually based on problem-specific Reynolds-averaged Navier-Stokes (RANS) methods. Access to detailed flow physics is attractive to industry, especially in an environment in which computer modelling is bound to play an ever increasing role. However, the improvement in accuracy and flow detail has substantial cost. This has so far prevented wider industrial use of LES. The purpose of the applied LES discussion meeting was to address questions regarding what is achievable and what is not, given the current technology and knowledge, for an industrial practitioner who is interested in using LES. The use of LES was explored in an application-centred context between diverse fields. The general flow-governing equation form was explored along with various LES models. The errors occurring in LES were analysed. Also, the hybridization of RANS and LES was considered. The importance of modelling relative to boundary conditions, problem definition and other more mundane aspects were examined. It was to an extent concluded that for LES to make most rapid industrial impact, pragmatic hybrid use of LES, implicit LES and RANS elements will probably be needed. Added to this further, highly industrial sector model parametrizations will be required with clear thought on the key target design parameter(s). The combination of good numerical modelling expertise, a sound understanding of turbulence, along with artistry, pragmatism and the use of recent developments in computer science should dramatically add impetus to the industrial uptake of LES. In the light of the numerous technical challenges that remain it appears that for some time to come LES will have echoes of the high levels of technical knowledge required for safe use of RANS but with much greater fidelity. PMID:19531503

  3. ALK+弥漫大B细胞淋巴瘤患者临床决策探讨%Clinical decision on a patient with ALK+diffuse large B cell lymphoma

    Institute of Scientific and Technical Information of China (English)

    董玲; 王先火; 王华庆; 付凯; 张会来; 孟斌; 张新伟; 宋秀宇; 张希梅; 翟琼莉; 刘霞; 侯芸; 李维

    2016-01-01

    Anaplastic lymphoma kinase (ALK)-positive diffuse large B-cell lymphoma (DLBCL) is a rare and distinct variant of DLBCL. It is classified as a unique subtype of DLBCL in the 2008 WHO classification of lymphomas. No standard and effective therapeutic regi-men is available for ALK+DLBCL because it shows a more aggressive clinical course and frequent relapse. Therefore, a standardized and individualized treatment is needed to benefit more patients diagnosed with ALK+DLBCL through a multiple disciplinary team. This arti-cle presents a case of an ALK+DLBCL patient who relapsed after transplantation and was successfully treated with the ALK kinase inhibi-tor Crizotinib.%ALK+弥漫大B细胞淋巴瘤(anaplastic lymphoma kinase-positive diffuse large B-cell lymphoma,ALK+DLBCL)是淋巴瘤中一种罕见的和具有明显差异性的病理类型,2008年WHO将其归类为DLBCL一个独特的亚型,该病侵袭性高,容易复发,目前尚无规范有效的治疗方案。采取多学科协作体系(multidisciplinary treatment,MDT)有利于制定规范化、个体化的治疗方案,探索针对ALK+DLBCL患者更有效的治疗方法,从而让更多的患者获益。本研究分享1例2012年1月天津医科大学肿瘤医院收治的ALK+DLBCL高剂量化疗联合自体造血干细胞移植(autologous hematopoietic stem cell transplantation,AHSCT)后复发,采用ALK激酶抑制剂克唑替尼(Crizotinib)治疗成功的案例。

  4. A novel molecular variant of the chimeric NPM-ALK transcript in Ki-1 positive large cell lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Ladanyi, M. [Memorial Sloan-Kettering Cancer Center, New York, NY (United States)

    1994-09-01

    The breakpoints of the t(2;5)(p23;q35), reported to be present in 30-40% of Ki-1 positive large cell lymphoma (Ki-1 LCL), have recently been cloned. They involve a novel tyrosine kinase gene, ALK, at 2p23 and the nucleophosmin gene, NPM, at 5q35. Reverse transcriptase polymerase chain reaction (RT-PCR) using NPM and ALK primers detects a consistent fusion product in Ki-1 cases with the translocation. We performed NPM-ALK RT-PCR on 16 cases of Ki-1 LCL, of which 13 had informative cytogenetics. Amplifiable template was confirmed in all samples by RT-PCR using {beta}-actin primers. Ten cases showed the expected 177 base pair (bp) RT-PCR product indicative of the translocation, including all 6 cases with cytogenetic evidence of the t(2;5) and 3 cases without 5q35 abnormalities. One additional case, which had uninformative cytogenetics, showed only a novel 144 bp RT-PCR product. Sequencing of this PCR product showed an in-frame junction of NPM to ALK, 20 bp distal to the usual NPM junction site and 53 bp distal to usual ALK junction site. The predicted chimeric protein is thus shorter by 11 amino acids, but the putative ALK catalytic domain remains intact. This case was a histologically typical anaplastic Ki-1 LCL which showed a clonal rearrangement of the T-cell receptor {beta} gene. The functional significance of this molecular variant and its relation to the exon structure of both genes require further study. The overall incidence of the translocation in this series, about 70%, is higher than suspected from cytogenetic analysis alone.

  5. Large for gestational age (LGA)

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002248.htm Large for gestational age (LGA) To use the sharing features on this page, please enable JavaScript. Large for gestational age means that a fetus or ...

  6. Large-D gravity and low-D strings.

    Science.gov (United States)

    Emparan, Roberto; Grumiller, Daniel; Tanabe, Kentaro

    2013-06-21

    We show that in the limit of a large number of dimensions a wide class of nonextremal neutral black holes has a universal near-horizon limit. The limiting geometry is the two-dimensional black hole of string theory with a two-dimensional target space. Its conformal symmetry explains the properties of massless scalars found recently in the large-D limit. For black branes with string charges, the near-horizon geometry is that of the three-dimensional black strings of Horne and Horowitz. The analogies between the α' expansion in string theory and the large-D expansion in gravity suggest a possible effective string description of the large-D limit of black holes. We comment on applications to several subjects, in particular to the problem of critical collapse. PMID:23829726

  7. Large deviations and idempotent probability

    CERN Document Server

    Puhalskii, Anatolii

    2001-01-01

    In the view of many probabilists, author Anatolii Puhalskii''s research results stand among the most significant achievements in the modern theory of large deviations. In fact, his work marked a turning point in the depth of our understanding of the connections between the large deviation principle (LDP) and well-known methods for establishing weak convergence results.Large Deviations and Idempotent Probability expounds upon the recent methodology of building large deviation theory along the lines of weak convergence theory. The author develops an idempotent (or maxitive) probability theory, introduces idempotent analogues of martingales (maxingales), Wiener and Poisson processes, and Ito differential equations, and studies their properties. The large deviation principle for stochastic processes is formulated as a certain type of convergence of stochastic processes to idempotent processes. The author calls this large deviation convergence.The approach to establishing large deviation convergence uses novel com...

  8. Influence of bromodeoxyuridine radiosensitization on malignant glioma patient survival: a retrospective comparison of survival data from the Northern California oncology group (NCOG) and radiation therapy oncology group trials (RTOG) for glioblastoma multiforme and anaplastic astrocytoma

    International Nuclear Information System (INIS)

    Purpose: To examine the effect of treatment using Bromodeoxyuridine (BrdU) during radiation therapy on malignant glioma patient survival by comparing historical survival data from several large clinical trials. Methods: A retrospective analysis of patient data from Radiation Therapy Oncology Group (RTOG) trials 74-01, 79-18, and 83-02 and the Northern California Oncology Group (NCOG) study 6G-82-1 was conducted. Patient data was supplied by both groups, and analyzed by the RTOG. Pretreatment characteristics including age, extent of surgery, Karnofsky Performance Status (KPS), and histopathology were collected; the only treatment variable evaluated was the use of BrdU during radiation therapy. Radiation dose, dose-fractionation schedule, use of chemotherapy, and/or type of chemotherapy was not controlled for in the analyses. Univariate and multivariate analyses were conducted to examine the potential treatment effect of BrdU on patient survival. Results: Data from 334 patients treated with BrdU on NCOG 6G-82-1 and 1743 patients treated without BrdU on 3 RTOG studies was received. Patients were excluded from the review if confirmation of eligibility could not be obtained, if the patient was ineligible for the study they entered, if central pathology review was not done, or if radiotherapy data was not available. Patients treated according to the RTOG studies had to start radiotherapy within 4 weeks of surgery; no such restriction existed for the NCOG studies. To ensure comparability between the studies, patients from the NCOG studies who began treatment longer than 40 days from surgery were also excluded. The final data set included 296 cases from the NCOG studies (89%) and 1478 cases from the RTOG studies (85%). For patients with glioblastoma multiforme (GBM) the median survival was 9.8 months in the RTOG studies and 13.0 months in the NCOG trial (p < 0.0001). For patients with AA the median survival was 35.1 months for the RTOG studies and 42.8 months in the NCOG

  9. Factors associated with sinus bradycardia during crizotinib treatment: a retrospective analysis of two large-scale multinational trials (PROFILE 1005 and 1007).

    Science.gov (United States)

    Ou, Sai-Hong Ignatius; Tang, Yiyun; Polli, Anna; Wilner, Keith D; Schnell, Patrick

    2016-04-01

    Decreases in heart rate (HR) have been described in patients receiving crizotinib. We performed a large retrospective analysis of HR changes during crizotinib therapy. HRs from vital-sign data for patients with anaplastic lymphoma kinase (ALK)-positive nonsmall cell lung cancer enrolled in PROFILE 1005 and the crizotinib arm of PROFILE 1007 were analyzed. Sinus bradycardia (SB) was defined as HR <60 beats per minute (bpm). Magnitude and timing of HR changes were assessed. Potential risk factors for SB were investigated by logistic regression analysis. Progression-free survival (PFS) was evaluated according to HR decrease by <20 versus ≥20 bpm within the first 50 days of starting treatment. For the 1053 patients analyzed, the mean maximum postbaseline HR decrease was 25 bpm (standard deviation 15.8). Overall, 441 patients (41.9%) had at least one episode of postbaseline SB. The mean precrizotinib treatment HR was significantly lower among patients with versus without postbaseline SB (82.2 bpm vs. 92.6 bpm). The likelihood of experiencing SB was statistically significantly higher among patients with a precrizotinib treatment HR <70 bpm. PFS was comparable among patients with or without HR decrease of ≥20 bpm within the first 50 days of starting crizotinib. Decrease in HR is very common among patients on crizotinib. The likelihood of experiencing SB was statistically significantly higher among patients with a precrizotinib treatment HR <70 bpm. This is the first large-scale report investigating the association between treatment with a tyrosine kinase inhibitor and the development of bradycardia. HRs should be closely monitored during crizotinib treatment. PMID:26823131

  10. How large is "large $N_c$" for Nuclear matter?

    CERN Document Server

    Torrieri, Giorgio

    2011-01-01

    We argue that a so far neglected dimensionless scale, the number of neighbors in a closely packed system, is relevant for the convergence of the large $N_c$ expansion at high chemical potential. It is only when the number of colors is large w.r.t. this new scale ($\\sim \\order{10}$) that a convergent large $N_c$ limit is reached. This provides an explanation as to why the large $N_c$ expansion, qualitatively successful in in vacuum QCD, fails to describe high baryo-chemical potential systems, such as nuclear matter. It also means that phenomenological claims about high density matter based on large $N_c$ extrapolations should be treated with caution.

  11. Large deviations and rain showers

    OpenAIRE

    Wilkinson, Michael

    2015-01-01

    Rainfall from ice-free cumulus clouds requires collisions of large numbers of microscopic droplets to create every raindrop. The onset of rain showers can be surprisingly rapid, much faster than the mean time required for a single collision. Large-deviation theory is used to explain this observation.

  12. Large amplitude oscillatory elongation flow

    DEFF Research Database (Denmark)

    Rasmussen, Henrik K.; Laillé, Philippe; Yu, Kaijia

    2008-01-01

    A filament stretching rheometer (FSR) was used for measuring the elongation flow with a large amplitude oscillative elongation imposed upon the flow. The large amplitude oscillation imposed upon the elongational flow as a function of the time t was defined as epsilon(t) =(epsilon) over dot(0)t...

  13. Querying Large Biological Network Datasets

    Science.gov (United States)

    Gulsoy, Gunhan

    2013-01-01

    New experimental methods has resulted in increasing amount of genetic interaction data to be generated every day. Biological networks are used to store genetic interaction data gathered. Increasing amount of data available requires fast large scale analysis methods. Therefore, we address the problem of querying large biological network datasets.…

  14. Large-scale data analytics

    CERN Document Server

    Gkoulalas-Divanis, Aris

    2014-01-01

    Provides cutting-edge research in large-scale data analytics from diverse scientific areas Surveys varied subject areas and reports on individual results of research in the field Shares many tips and insights into large-scale data analytics from authors and editors with long-term experience and specialization in the field

  15. Large deviations on Markov towers

    International Nuclear Information System (INIS)

    We give a sufficient condition to hold a full large deviation principle for Markov tower maps induced from return time functions. As an application of this result we show the large deviation principle of level 2 for some class of smooth dynamical systems with nonuniform hyperbolicity

  16. Large deviations and rain showers

    CERN Document Server

    Wilkinson, Michael

    2016-01-01

    Rainfall from ice-free cumulus clouds requires collisions of large numbers of microscopic droplets to create every raindrop. The onset of rain showers can be surprisingly rapid, much faster than the mean time required for a single collision. Large-deviation theory is used to explain this observation.

  17. Large shareholders and accounting research

    Institute of Scientific and Technical Information of China (English)

    Ole-Kristian; Hope

    2013-01-01

    Large shareholders are a potentially very important element of firms’ corporate governance system. Whereas analytical research is typically vague on who these large shareholders are, in practice there are important variations in the types of large owners(and the different types of large owners could play very different governance roles). After briefly reviewing the standard agency cost arguments, in this article I emphasize the heterogeneity of concentrated ownership and in particular focus on the roles of families, institutions, governments, and employee ownership. I also discuss the role of large shareholders in private(i.e., unlisted) firms, where ownership tends to be more concentrated than in publicly traded firms. Finally, I briefly discuss variations in ownership structures across selected countries.

  18. Graphs of Large Girth and Surfaces of Large Systole

    OpenAIRE

    Petri, Bram; Walker, Alexander

    2015-01-01

    The systole of a hyperbolic surface is bounded by a logarithmic function of its genus. This bound is sharp, in that there exist sequences of surfaces with genera tending to infinity that attain logarithmically large systoles. These are constructed by taking congruence covers of arithmetic surfaces. In this article we provide a new construction for a sequence of surfaces with systoles that grow logarithmically in their genera. We do this by combining a construction for graphs of large girth an...

  19. Management of small-cell anaplastic carcinoma, 1980-1982

    International Nuclear Information System (INIS)

    The author gives an updated report on the management of small-cell carcinoma of the lung, particularly on staging and therapy. He presents and discusses data accumulated from the literature published in 1980 and 1981 and finishes with 9 conclusions regarding treatment of these carcinomas. Of interest are the following: combined use of chemotherapy and radiotherapy is clearly superior to radiotherapy alone; prophylactic brain irradiation decreases the incidence of brain metastases, but it does not change the overall median survival. It should probably be restricted to patients who have achieved complete remission; radiotherapy to the primary tumor and including the regional lymph nodes decreases the rate of local recurrence, but it does not influence the median survival when given with combination chemotherapy. The morbidity of the combined modality of therapy is considerably higher than when using chemotherapy alone. Whether the percentage of long-term remission survivors is higher when the combined modality of therapy is used, is still uncertain. (C.F.)

  20. Measuring happiness in large population

    Science.gov (United States)

    Wenas, Annabelle; Sjahputri, Smita; Takwin, Bagus; Primaldhi, Alfindra; Muhamad, Roby

    2016-01-01

    The ability to know emotional states for large number of people is important, for example, to ensure the effectiveness of public policies. In this study, we propose a measure of happiness that can be used in large scale population that is based on the analysis of Indonesian language lexicons. Here, we incorporate human assessment of Indonesian words, then quantify happiness on large-scale of texts gathered from twitter conversations. We used two psychological constructs to measure happiness: valence and arousal. We found that Indonesian words have tendency towards positive emotions. We also identified several happiness patterns during days of the week, hours of the day, and selected conversation topics.

  1. Large surface micro machining system

    International Nuclear Information System (INIS)

    Large surface micro machining system is integrated with a series of machining process for manufacturing the large surface ultra-precision products with micro feature array. It is required to be able to produce larger surface, more complicated feature with smaller size shown as the case of the light guide plate, prism sheet, defusion film and renticular lens. Technical trends of the large surface micro machining system is introduced in this paper. The contents of a national project with the same title is also introduced briefly

  2. Phenomenology of large Nc QCD

    International Nuclear Information System (INIS)

    These lectures are designed to introduce the methods and results of large Nc QCD in a presentation intended for nuclear and particle physicists alike. Beginning with definitions and motivations of the approach, we demonstrate that all quark and gluon Feynman diagrams are organized into classes based on powers of 1/Nc. We then show that this result can be translated into definite statements about mesons and baryons containing arbitrary numbers of constituents. In the mesons, numerous well-known phenomenological properties follow as immediate consequences of simply counting powers of Nc, while for the baryons, quantitative large Nc analyses of masses and other properties are seen to agree with experiment, even when 'large' Nc is set equal to its observed value of 3. Large Nc reasoning is also used to explain some simple features of nuclear interactions. (author)

  3. Large Hadron Collider nears completion

    CERN Multimedia

    2008-01-01

    Installation of the final component of the Large Hadron Collider particle accelerator is under way along the Franco-Swiss border near Geneva, Switzerland. When completed this summer, the LHC will be the world's largest and most complex scientific instrument.

  4. Optimization theory for large systems

    CERN Document Server

    Lasdon, Leon S

    2011-01-01

    Important text examines most significant algorithms for optimizing large systems and clarifying relations between optimization procedures. Much data appear as charts and graphs and will be highly valuable to readers in selecting a method and estimating computer time and cost in problem-solving. Initial chapter on linear and nonlinear programming presents all necessary background for subjects covered in rest of book. Second chapter illustrates how large-scale mathematical programs arise from real-world problems. Appendixes. List of Symbols.

  5. Large Fibroepithelial Polyp of Vulva

    OpenAIRE

    Sujaya V Rao; Nagarathna G.; Mahesha H Navada; Bhat, Poornima Ramachandra B.

    2011-01-01

    A rare case of a large fibroepithelial polyp (FEP) of the vulva is described. The polypoidal growth was 10 cm in its largest diameter, having a long pedicle with features of inflammation secondary to infection, and was found arising from the left labia majora. The patient did not manifest any signs of recurrence following excision. A large and infected FEP of the vulva is a rare occurrence and hence reported.

  6. Large-scale solar heat

    Energy Technology Data Exchange (ETDEWEB)

    Tolonen, J.; Konttinen, P.; Lund, P. [Helsinki Univ. of Technology, Otaniemi (Finland). Dept. of Engineering Physics and Mathematics

    1998-12-31

    In this project a large domestic solar heating system was built and a solar district heating system was modelled and simulated. Objectives were to improve the performance and reduce costs of a large-scale solar heating system. As a result of the project the benefit/cost ratio can be increased by 40 % through dimensioning and optimising the system at the designing stage. (orig.)

  7. Sustainability in Large Power Plants

    OpenAIRE

    Faria, Roberto Censi; Kniess, Cláudia Terezinha; Maccari, Emerson Antonio

    2012-01-01

    No business activity today can be implemented without take into account the aspects of sustainability. The concept of sustainable development that was born of the years 1970 and 1980 and was enshrined in the concept of the three pillars of John Elkington - economic, social and environmental issues, the "triple bottom line" is a constraint for all types of enterprises, especially for large hydropower plants. Large hydropower plants have been for a while the great enemy of development, because ...

  8. LSD: Large Survey Database framework

    Science.gov (United States)

    Juric, Mario

    2012-09-01

    The Large Survey Database (LSD) is a Python framework and DBMS for distributed storage, cross-matching and querying of large survey catalogs (>10^9 rows, >1 TB). The primary driver behind its development is the analysis of Pan-STARRS PS1 data. It is specifically optimized for fast queries and parallel sweeps of positionally and temporally indexed datasets. It transparently scales to more than >10^2 nodes, and can be made to function in "shared nothing" architectures.

  9. Quantum spin liquids: a large-S route

    OpenAIRE

    Tchernyshyov, Oleg

    2003-01-01

    This paper explores the large-S route to quantum disorder in the Heisenberg antiferromagnet on the pyrochlore lattice and its homologues in lower dimensions. It is shown that zero-point fluctuations of spins shape up a valence-bond solid at low temperatures for one two-dimensional lattice and a liquid with very short-range valence-bond correlations for another. A one-dimensional model demonstrates potential significance of quantum interference effects (as in Haldane's gap): the quantum meltin...

  10. Preparation of large monodisperse vesicles.

    Directory of Open Access Journals (Sweden)

    Ting F Zhu

    Full Text Available Preparation of monodisperse vesicles is important both for research purposes and for practical applications. While the extrusion of vesicles through small pores (approximately 100 nm in diameter results in relatively uniform populations of vesicles, extrusion to larger sizes results in very heterogeneous populations of vesicles. Here we report a simple method for preparing large monodisperse multilamellar vesicles through a combination of extrusion and large-pore dialysis. For example, extrusion of polydisperse vesicles through 5-microm-diameter pores eliminates vesicles larger than 5 microm in diameter. Dialysis of extruded vesicles against 3-microm-pore-size polycarbonate membranes eliminates vesicles smaller than 3 microm in diameter, leaving behind a population of monodisperse vesicles with a mean diameter of approximately 4 microm. The simplicity of this method makes it an effective tool for laboratory vesicle preparation with potential applications in preparing large monodisperse liposomes for drug delivery.

  11. Dijets at large rapidity intervals

    CERN Document Server

    Pope, B G

    2001-01-01

    Inclusive diet production at large pseudorapidity intervals ( Delta eta ) between the two jets has been suggested as a regime for observing BFKL dynamics. We have measured the dijet cross section for large Delta eta in pp collisions at square root s = 1800 and 630 GeV using the DOE detector. The partonic cross section increases strongly with the size of Delta eta . The observed growth is even stronger than expected on the basis of BFKL resummation in the leading logarithmic approximation. The growth of the partonic cross section can be accommodated with an effective BFKL intercept of alpha /sub BFKL/(20 GeV) = 1.65 +or- 0.07.

  12. Rindler force at large distances

    CERN Document Server

    Grumiller, Daniel

    2011-01-01

    Given some assumptions it is possible to derive the most general theory of gravity at large distances. The force law derived from this theory contains a Rindler term in addition to well-known contributions, a Schwarzschild mass and a cosmological constant. The same force law recently was confronted with solar system precision data. The Rindler force, if present in Nature, has intriguing consequences for gravity at large distances. In particular, the Rindler force is capable of explaining about 10% of the Pioneer anomaly and simultaneously ameliorates the shape of galactic rotation curves.

  13. Large scale biomimetic membrane arrays

    DEFF Research Database (Denmark)

    Hansen, Jesper Søndergaard; Perry, Mark; Vogel, Jörg;

    2009-01-01

    peptides and proteins. Next, we tested the scalability of the biomimetic membrane design by establishing lipid bilayers in rectangular 24 x 24 and hexagonal 24 x 27 aperture arrays, respectively. The results presented show that the design is suitable for further developments of sensitive biosensor assays......To establish planar biomimetic membranes across large scale partition aperture arrays, we created a disposable single-use horizontal chamber design that supports combined optical-electrical measurements. Functional lipid bilayers could easily and efficiently be established across CO2 laser micro......, and furthermore demonstrate that the design can conveniently be scaled up to support planar lipid bilayers in large square-centimeter partition arrays....

  14. Intracranial Large Artery Occlusive Disease

    Institute of Scientific and Technical Information of China (English)

    Wong KS; Li H; Kay R

    2000-01-01

    @@Intracranial large artery stenosis is the most commonly found vascular lesion in stroke patient of Chinese, Hispanic and African ancestry. There .have been few studies on the epidemiology, pathophysiology, treatment and prognosis of this important disease. Recent advances in technology provide safe and reliable investigation for studying large number of patients. Transcranial Doppler is an easily accessible, cheap and reliable method to diagnose intracranial stenosis. It is suitable for screening for and monitoring the progress of intracranial stenosis. Magnetic resonance angiography and CT angiography provide the morphology of lumenal stenosis but are less accessible.

  15. Structuring very large domain models

    DEFF Research Database (Denmark)

    Störrle, Harald

    2010-01-01

    a lower level of detail have not been dealt with. This paper aims at filling this gap by reporting personal experiences from a very large scale industrial domain modeling project. There, structuring the logical view turned out to be a critical success factor. We explain the project and its setting......, analyze the role and repercussions of model structuring, and examine the implications model structuring decisions have on other parts of the project. We then explain the model structure abstracted from a very large scale industrial modeling project. Finally, we discuss lessons learned....

  16. The Limit of Large Vessels

    Institute of Scientific and Technical Information of China (English)

    Yang Peiju

    2011-01-01

    On Feb 21(st),the industry was shocked by the news that AP Moller-Maersk placed an order of 10 container ships of 18,000 TEU with the South Korean ship yards.The order brings the development of large vessels to a new climax and at the same time puts forward a series of research subjects to the industry,such as what is the limit for the development of large vessels,whether ship safety can be guaranteed,and etc.

  17. Large superconducting wind turbine generators

    DEFF Research Database (Denmark)

    Abrahamsen, Asger Bech; Magnusson, Niklas; Jensen, Bogi Bech;

    2012-01-01

    To realize large (>10 MW) direct-driven off-shore wind turbines, a number of steps are needed to reduce weight and cost compared to on-shore technologies. One of the major challenges is to provide drive trains which can comply with the large torque as the turbine rotor diameter is scaled up and the...... thereby having a smaller size and weight [1, 2]. A 5 MW superconducting wind turbine generator forms the basics for the feasibility considerations, particularly for the YBCO and MgB2 superconductors entering the commercial market. Initial results indicate that a 5 MW generator with an active weight of 34...

  18. Physics with large extra dimensions

    Indian Academy of Sciences (India)

    Ignatios Antoniadis

    2004-02-01

    The recent understanding of string theory opens the possibility that the string scale can be as low as a few TeV. The apparent weakness of gravitational interactions can then be accounted by the existence of large internal dimensions, in the sub-millimeter region. Furthermore, our world must be confined to live on a brane transverse to these large dimensions, with which it interacts only gravitationally. In my lecture, I describe briefly this scenario which gives a new theoretical framework for solving the gauge hierarchy problem and the unification of all interactions. I also discuss a minimal embedding of the standard model, gauge coupling unification and proton stability.

  19. Ultrasonic large aperture imaging system

    International Nuclear Information System (INIS)

    A new ultrasonic large aperture imaging technique is described. This device combines a focussed transducer as a transmitter, producing a small ultrasonic beam, with N transducers as receivers. We show that is possible to considerably reduce the number of receivers if, on the one hand, we limit the reconstitution process to the emitter beam area and, on the other hand, we ensure that the artefacts, caused by the spatial sampling of the reception, are outside this area. Under these conditions, the result is a high resolution image which does not require large reconstitution processing times. Theoretical and experimental results are given

  20. Cutaneous CD30-positive lymphoproliferations : clinical and molecular aspects and differential diagnosis

    NARCIS (Netherlands)

    Benner, Marchina Frederika

    2012-01-01

    The studies presented in this thesis focused on cutaneous CD30-positive lymphoproliferations, particularly on primary cutaneous anaplastic large cell lymphoma (C-ALCL), a distinct type of cutaneous T-cell lymphoma (CTCL). In the initial staging of patients with an anaplastic large cell lymphoma firs

  1. Large program implementation on minicomputers

    CERN Document Server

    Fonti, L

    1980-01-01

    A method is described to fit a very large program (usually executed on very big mainframes, like a CDC 7600 or IBM 370/168) on a 16-bit minicomputer with memory management support. The method outlined is fully general, even if references are made to a specific example: the implementation of the CERN program HYDRA on a PDP 11/70. (2 refs).

  2. Inconsistency in large pharmacogenomic studies

    DEFF Research Database (Denmark)

    Haibe-Kains, Benjamin; El-Hachem, Nehme; Birkbak, Nicolai Juul;

    2013-01-01

    Two large-scale pharmacogenomic studies were published recently in this journal. Genomic data are well correlated between studies; however, the measured drug response data are highly discordant. Although the source of inconsistencies remains uncertain, it has potential implications for using these...

  3. The very large hadron collider

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-09-01

    This paper reviews the purposes to be served by a very large hadron collider and the organization and coordination of efforts to bring it about. There is some discussion of magnet requirements and R&D and the suitability of the Fermilab site.

  4. Large gap magnetic suspension system

    Science.gov (United States)

    Abdelsalam, Moustafa K.; Eyssa, Y. M.

    1991-01-01

    The design of a large gap magnetic suspension system is discussed. Some of the topics covered include: the system configuration, permanent magnet material, levitation magnet system, superconducting magnets, resistive magnets, superconducting levitation coils, resistive levitation coils, levitation magnet system, and the nitrogen cooled magnet system.

  5. COOPERATIVE LEARNING IN LARGE CLASSES

    Institute of Scientific and Technical Information of China (English)

    GuoXiangju

    2004-01-01

    Teaching college English in large classes is a new challenge to teachers. To meet this challenge, the strategy of cooperative learning is practicable. This paper introduces cooperative learning and describes the experiment results, which prove the advantages of cooperative learning over competitive learning or individualistic learning.

  6. Active Learning in Large Classes

    DEFF Research Database (Denmark)

    Gørtz, Inge Li

    2011-01-01

    teaching large classes (more than 50 students), and describe how we successfully have in a second semester course in the Bachelor of Engineering (BEng) and Bachelor of Science Engineering (BSc Eng) program at the Technical University of Denmark (DTU). Approximately 200 students is attending the...

  7. Large Hadron Collider nears completion

    CERN Multimedia

    2008-01-01

    Installation of the final component of the Large Hadron Collider particle accelerator is under way along the Franco-Swiss border near Geneva, Switzerland. When completed this summer, the LHC will be the world's largest and most complex scientific instrument. It is being constructed by the European Organization for Nuclear Research, one of the world's largest particle physics laboratories.

  8. Large area CMOS image sensors

    International Nuclear Information System (INIS)

    CMOS image sensors, also known as CMOS Active Pixel Sensors (APS) or Monolithic Active Pixel Sensors (MAPS), are today the dominant imaging devices. They are omnipresent in our daily life, as image sensors in cellular phones, web cams, digital cameras, ... In these applications, the pixels can be very small, in the micron range, and the sensors themselves tend to be limited in size. However, many scientific applications, like particle or X-ray detection, require large format, often with large pixels, as well as other specific performance, like low noise, radiation hardness or very fast readout. The sensors are also required to be sensitive to a broad spectrum of radiation: photons from the silicon cut-off in the IR down to UV and X- and gamma-rays through the visible spectrum as well as charged particles. This requirement calls for modifications to the substrate to be introduced to provide optimized sensitivity. This paper will review existing CMOS image sensors, whose size can be as large as a single CMOS wafer, and analyse the technical requirements and specific challenges of large format CMOS image sensors.

  9. Large Scale Glazed Concrete Panels

    DEFF Research Database (Denmark)

    Bache, Anja Margrethe

    2010-01-01

    Factories and finally Lene Tranberg and Bøje Lungård’s Elsinore water purification plant. These buildings have qualities that I would like applied, perhaps transformed or most preferably, if possible, interpreted anew, for the large glazed concrete panels I shall develop. The article is ended and concluded...

  10. Qatar - large capital investment planned

    International Nuclear Information System (INIS)

    Large capital investments are planned throughout Qatar's energy industry over the next five years totalling $25 billion. This article describes the successful commissioning of Qatar's first liquefied natural gas (LNG) project on time and within budget. The second LNG plant is well underway and plans for a third are under negotiation. (UK)

  11. Large deviations and portfolio optimization

    Science.gov (United States)

    Sornette, Didier

    Risk control and optimal diversification constitute a major focus in the finance and insurance industries as well as, more or less consciously, in our everyday life. We present a discussion of the characterization of risks and of the optimization of portfolios that starts from a simple illustrative model and ends by a general functional integral formulation. A major item is that risk, usually thought of as one-dimensional in the conventional mean-variance approach, has to be addressed by the full distribution of losses. Furthermore, the time-horizon of the investment is shown to play a major role. We show the importance of accounting for large fluctuations and use the theory of Cramér for large deviations in this context. We first treat a simple model with a single risky asset that exemplifies the distinction between the average return and the typical return and the role of large deviations in multiplicative processes, and the different optimal strategies for the investors depending on their size. We then analyze the case of assets whose price variations are distributed according to exponential laws, a situation that is found to describe daily price variations reasonably well. Several portfolio optimization strategies are presented that aim at controlling large risks. We end by extending the standard mean-variance portfolio optimization theory, first within the quasi-Gaussian approximation and then using a general formulation for non-Gaussian correlated assets in terms of the formalism of functional integrals developed in the field theory of critical phenomena.

  12. Protection of large capacitor banks

    International Nuclear Information System (INIS)

    Large capacitor banks, as used in many pulsed plasma experiments, are subject to catastrophic failure in the event of a short in the output or in an individual capacitor. Methods are described for protecting such banks to minimize the damage and down-time caused by such a failure

  13. Strategic Management of Large Projects

    Institute of Scientific and Technical Information of China (English)

    WangYingluo; LiuYi; LiYuan

    2004-01-01

    The strategic management of large projects is both theoretically and practically important. Some scholars have advanced flexible strategy theory in China. The difference of strategic flexibility and flexible strategy is pointed out. The supporting system and characteristics of flexible strategy are analyzed. The changes of flexible strategy and integration of strategic management are discussed.

  14. Large molten pool heat transfer

    International Nuclear Information System (INIS)

    This workshop on large molten pool heat transfer is composed of 5 sessions which titles are: feasibility of in-vessel core debris cooling; experiments on molten pool heat transfer; calculational efforts on molten pool convection; heat transfer to the surrounding water, experimental techniques; future experiments and ex-vessel studies (RASPLAV, TOLBIAC, BALI, SULTAN, CORVIS, VULCANO, CORINE programs)

  15. Neutrinos Confronting Large Extra Dimensions

    CERN Document Server

    Maalampi, J; Vilja, I

    2001-01-01

    We study neutrino physics in a model with one large extra dimension. We assume the existence of two four-dimensional branes in the five-dimensional space-time, one for the ordinary particles and the other one for mirror particles, and we investigate neutrino masses and mixings in this scheme. Comparison of experimental neutrino data with the predictions of the model leads to various restrictions on the parameters of the model. For instance, the size of the extra dimension, R, turns out to be bounded from below. Cosmological considerations seem to favor a large R. The usual mixing schemes proposed as solutions to the solar and atmospheric neutrino anomalies are compatible with our model.

  16. Large Aspect Ratio Tokamak Study

    International Nuclear Information System (INIS)

    The Large Aspect Ratio Tokamak Study (LARTS) at Oak Ridge National Laboratory (ORNL) investigated the potential for producing a viable longburn tokamak reactor by enhancing the volt-second capability of the ohmic heating transformer through the use of high aspect ratio designs. The plasma physics, engineering, and economic implications of high aspect ratio tokamaks were assessed in the context of extended burn operation. Using a one-dimensional transport code plasma startup and burn parameters were addressed. The pulsed electrical power requirements for the poloidal field system, which have a major impact on reactor economics, were minimized by optimizing the startup and shutdown portions of the tokamak cycle. A representative large aspect ratio tokamak with an aspect ratio of 8 was found to achieve a burn time of 3.5 h at capital cost only approx. 25% greater than that of a moderate aspect ratio design tokamak

  17. Physics with large extra dimensions

    CERN Document Server

    Antoniadis, Ignatios

    2004-01-01

    The recent understanding of string theory opens the possibility that the string scale can be as low as a few TeV. The apparent weakness of gravitational interactions can then be accounted by the existence of large internal dimensions, in the submillimeter region. Furthermore, our world must be confined to live on a brane transverse to these large dimensions, with which it interacts only gravitationally. In my lecture, I describe briefly this scenario which gives a new theoretical framework for solving the gauge hierarchy problem and the unification of all interactions. I also discuss its main properties and implications for observations at both future particle colliders, and in non-accelerator gravity experiments. Such effects are for instance the production of Kaluza-Klein resonances, graviton emission in the bulk of extra dimensions, and a radical change of gravitational forces in the submillimeter range.

  18. Chunking of Large Multidimensional Arrays

    Energy Technology Data Exchange (ETDEWEB)

    Rotem, Doron; Otoo, Ekow J.; Seshadri, Sridhar

    2007-02-28

    Data intensive scientific computations as well on-lineanalytical processing applications as are done on very large datasetsthat are modeled as k-dimensional arrays. The storage organization ofsuch arrays on disks is done by partitioning the large global array intofixed size hyper-rectangular sub-arrays called chunks or tiles that formthe units of data transfer between disk and memory. Typical queriesinvolve the retrieval of sub-arrays in a manner that accesses all chunksthat overlap the query results. An important metric of the storageefficiency is the expected number of chunks retrieved over all suchqueries. The question that immediately arises is "what shapes of arraychunks give the minimum expected number of chunks over a query workload?"In this paper we develop two probabilistic mathematical models of theproblem and provide exact solutions using steepest descent and geometricprogramming methods. Experimental results, using synthetic workloads onreal life data sets, show that our chunking is much more efficient thanthe existing approximate solutions.

  19. Structure functions at large x

    CERN Document Server

    Zhang, Z

    2002-01-01

    Structure function data together with other measurements from fixed-target deep inelastic scattering and hadron-hadron collider experiments which contribute to our knowledge of the parton density functions are reviewed. The inclusive cross-section measurements of neutral and charged current interactions at HERA are presented and their impact on the parton density functions is discussed. Future prospects for an improved knowledge of the parton density functions at large x are briefly mentioned.

  20. Additive Manufacturing for Large Products

    OpenAIRE

    Leirvåg, Roar Nelissen

    2013-01-01

    This thesis researches the possibility and feasibility of applying additive manufacturing technology in the manufacturing of propellers. The thesis concerns the production at the foundry Oshaug Metall AS. Their products consist of propellers and other large products cast in Nickel-Aluminium Bronze. This report looks at three approaches and applications for additive manufacturing at the foundry. These are additively manufactured pattern, sand mold and end metal parts. The available \\emph{State...

  1. Very large solid angle spectrometers

    International Nuclear Information System (INIS)

    The basic conditions of coincidence experiments are discussed and some of the properties of specific detectors covering up to 90% of 4π steradian and presenting a very large momentum bite are shown. It will appear that such detectors, compared to classical iron dipole spectrometers, present larger acceptances, but a smaller resolving power and a rather low background rejection. The choice of which of these two solutions is to be used depends on the conditions of the specific experiments

  2. Large floating structures technological advances

    CERN Document Server

    Wang, BT

    2015-01-01

    This book surveys key projects that have seen the construction of large floating structures or have attained detailed conceptual designs. This compilation of key floating structures in a single volume captures the innovative features that mark the technological advances made in this field of engineering, and will provide a useful reference for ideas, analysis, design, and construction of these unique and emerging urban projects to offshore and marine engineers, urban planners, architects and students.

  3. Quantum ergodicity on large graphs

    OpenAIRE

    Anantharaman, Nalini

    2015-01-01

    We give three different proofs of the main result of Anantharaman-Le Masson, establishing quantum ergodicity -- a form of delocalization --for eigenfunctions of the laplacian on large regular graphs of fixed degree. These three proofs are much shorter than the original one, quite different from one another, and we feelthat each of the four proofs sheds a different light on the problem. The goal of this exploration is to find a proof that could be adapted for othermodels of interest in mathema...

  4. Testing gravity on Large Scales

    OpenAIRE

    Raccanelli Alvise

    2013-01-01

    We show how it is possible to test general relativity and different models of gravity via Redshift-Space Distortions using forthcoming cosmological galaxy surveys. However, the theoretical models currently used to interpret the data often rely on simplifications that make them not accurate enough for precise measurements. We will discuss improvements to the theoretical modeling at very large scales, including wide-angle and general relativistic corrections; we then show that for wide and deep...

  5. Irradiation injury to large arteries

    International Nuclear Information System (INIS)

    Four cases of irradiation injury to large arteries following radiotherapy treatment are presented and the literature is reviewed. Three patterns of injury have emerged: 1) intimal damage resulting in mural thrombosis presenting within 5 years of irradiation, 2) fibrotic occlusion presenting within 10 years of injury, and 3) a predisposition to the development of atheroma together with periarterial fibrosis associated with a latent interval of 20 or more years. The treatment of choice is a bypass procedure of the arterial lesion. (author)

  6. Large Scale Nanolaminate Deformable Mirror

    Energy Technology Data Exchange (ETDEWEB)

    Papavasiliou, A; Olivier, S; Barbee, T; Miles, R; Chang, K

    2005-11-30

    This work concerns the development of a technology that uses Nanolaminate foils to form light-weight, deformable mirrors that are scalable over a wide range of mirror sizes. While MEMS-based deformable mirrors and spatial light modulators have considerably reduced the cost and increased the capabilities of adaptive optic systems, there has not been a way to utilize the advantages of lithography and batch-fabrication to produce large-scale deformable mirrors. This technology is made scalable by using fabrication techniques and lithography that are not limited to the sizes of conventional MEMS devices. Like many MEMS devices, these mirrors use parallel plate electrostatic actuators. This technology replicates that functionality by suspending a horizontal piece of nanolaminate foil over an electrode by electroplated nickel posts. This actuator is attached, with another post, to another nanolaminate foil that acts as the mirror surface. Most MEMS devices are produced with integrated circuit lithography techniques that are capable of very small line widths, but are not scalable to large sizes. This technology is very tolerant of lithography errors and can use coarser, printed circuit board lithography techniques that can be scaled to very large sizes. These mirrors use small, lithographically defined actuators and thin nanolaminate foils allowing them to produce deformations over a large area while minimizing weight. This paper will describe a staged program to develop this technology. First-principles models were developed to determine design parameters. Three stages of fabrication will be described starting with a 3 x 3 device using conventional metal foils and epoxy to a 10-across all-metal device with nanolaminate mirror surfaces.

  7. Elliptic Flow at Large Viscosity

    OpenAIRE

    Koch, Volker

    2009-01-01

    In this contribution we present an alternative scenario for the large elliptic flow observed in relativistic heavy ion collisions. Motivated by recent results from Lattice QCD on flavor off-diagonal susceptibilities we argue that the matter right above $T_{c}$ can be described by single-particle dynamics in a repulsive single-particle potential, which in turn gives rise to elliptic flow. These ideas can be tested experimentally by measuring elliptic flow of heavy quarks, preferably via the me...

  8. Large fused GPU volume rendering

    OpenAIRE

    Lindholm, Stefan

    2008-01-01

    This master thesis describes the underlying theory and implementation of a fused GPU volume rendering pipeline. The open source framework of XIP, largely developed at Siemens Corporate Research, is extended with fusion capabilities through a Binary Space Partitioning approach. Regions in the intersection pattern of multiple volumes are identified and subsequently rendered using either Texture Slicing or Raycasting in a cell based fashion. Results demonstrate interactive frame rates for reason...

  9. Correlations between large prime numbers

    OpenAIRE

    Bershadskii, A.

    2011-01-01

    It is shown that short-range correlations between large prime numbers (~10^5 and larger) have a Poissonian nature. Correlation length \\zeta = 4.5 for the primes ~10^5 and it is increasing logarithmically according to the prime number theorem. For moderate prime numbers (~10^4) the Poissonian distribution is not applicable while the correlation length surprisingly continues to follow to the logarithmical law. A chaotic (deterministic) hypothesis has been suggested to explain the moderate prime...

  10. Aggregation in Large Dynamic Panels

    OpenAIRE

    Pesaran, Mohammad Hashem; Chudik, Alexander

    2011-01-01

    This paper considers the problem of aggregation in the case of large linear dynamic panels, where each micro unit is potentially related to all other micro units, and where micro innovations are allowed to be cross sectionally dependent. Following Pesaran (2003), an optimal aggregate function is derived, and the limiting behavior of the aggregation error is investigated as N (the number of cross section units) increases. Certain distributional features of micro parameters are also identi...

  11. Models of large scale structure

    International Nuclear Information System (INIS)

    The ingredients required to construct models of the cosmic large scale structure are discussed. Input from particle physics leads to a considerable simplification by offering concrete proposals for the geometry of the universe, the nature of the dark matter and the primordial fluctuations that seed the growth of structure. The remaining ingredient is the physical interaction that governs dynamical evolution. Empirical evidence provided by an analysis of a redshift survey of IRAS galaxies suggests that gravity is the main agent shaping the large-scale structure. In addition, this survey implies large values of the mean cosmic density, Ω> or approx.0.5, and is consistent with a flat geometry if IRAS galaxies are somewhat more clustered than the underlying mass. Together with current limits on the density of baryons from Big Bang nucleosynthesis, this lends support to the idea of a universe dominated by non-baryonic dark matter. Results from cosmological N-body simulations evolved from a variety of initial conditions are reviewed. In particular, neutrino dominated and cold dark matter dominated universes are discussed in detail. Finally, it is shown that apparent periodicities in the redshift distributions in pencil-beam surveys arise frequently from distributions which have no intrinsic periodicity but are clustered on small scales. (orig.)

  12. Large wood recruitment and transport during large floods: A review

    Science.gov (United States)

    Comiti, F.; Lucía, A.; Rickenmann, D.

    2016-09-01

    Large wood (LW) elements transported during large floods are long known to have the capacity to induce dangerous obstructions along the channel network, mostly at bridges and at hydraulic structures such as weirs. However, our current knowledge of wood transport dynamics during high-magnitude flood events is still very scarce, mostly because these are (locally) rare and thus unlikely to be directly monitored. Therefore, post-event surveys are invaluable ways to get insights (although indirectly) on LW recruitment processes, transport distance, and factors inducing LW deposition - all aspects that are crucial for the proper management of river basins related to flood hazard mitigation. This paper presents a review of the (quite limited) literature available on LW transport during large floods, drawing extensively on the authors' own experience in mountain and piedmont rivers, published and unpublished. The overall picture emerging from these studies points to a high, catchment-specific variability in all the different processes affecting LW dynamics during floods. Specifically, in the LW recruitment phase, the relative floodplain (bank erosion) vs. hillslope (landslide and debris flows) contribution in mountain rivers varies substantially, as it relates to the extent of channel widening (which depends on many variables itself) but also to the hillslope-channel connectivity of LW mobilized on the slopes. As to the LW transport phase within the channel network, it appears to be widely characterized by supply-limited conditions; whereby LW transport rates (and thus volumes) are ultimately constrained by the amount of LW that is made available to the flow. Indeed, LW deposition during floods was mostly (in terms of volume) observed at artificial structures (bridges) in all the documented events. This implies that the estimation of LW recruitment and the assessment of clogging probabilities for each structure (for a flood event of given magnitude) are the most important

  13. Large-bore pipe decontamination

    International Nuclear Information System (INIS)

    The decontamination and decommissioning (D and D) of 1200 buildings within the US Department of Energy-Office of Environmental Management (DOE-EM) Complex will require the disposition of miles of pipe. The disposition of large-bore pipe, in particular, presents difficulties in the area of decontamination and characterization. The pipe is potentially contaminated internally as well as externally. This situation requires a system capable of decontaminating and characterizing both the inside and outside of the pipe. Current decontamination and characterization systems are not designed for application to this geometry, making the direct disposal of piping systems necessary in many cases. The pipe often creates voids in the disposal cell, which requires the pipe to be cut in half or filled with a grout material. These methods are labor intensive and costly to perform on large volumes of pipe. Direct disposal does not take advantage of recycling, which could provide monetary dividends. To facilitate the decontamination and characterization of large-bore piping and thereby reduce the volume of piping required for disposal, a detailed analysis will be conducted to document the pipe remediation problem set; determine potential technologies to solve this remediation problem set; design and laboratory test potential decontamination and characterization technologies; fabricate a prototype system; provide a cost-benefit analysis of the proposed system; and transfer the technology to industry. This report summarizes the activities performed during fiscal year 1997 and describes the planned activities for fiscal year 1998. Accomplishments for FY97 include the development of the applicable and relevant and appropriate regulations, the screening of decontamination and characterization technologies, and the selection and initial design of the decontamination system

  14. Large-bore pipe decontamination

    Energy Technology Data Exchange (ETDEWEB)

    Ebadian, M.A.

    1998-01-01

    The decontamination and decommissioning (D and D) of 1200 buildings within the US Department of Energy-Office of Environmental Management (DOE-EM) Complex will require the disposition of miles of pipe. The disposition of large-bore pipe, in particular, presents difficulties in the area of decontamination and characterization. The pipe is potentially contaminated internally as well as externally. This situation requires a system capable of decontaminating and characterizing both the inside and outside of the pipe. Current decontamination and characterization systems are not designed for application to this geometry, making the direct disposal of piping systems necessary in many cases. The pipe often creates voids in the disposal cell, which requires the pipe to be cut in half or filled with a grout material. These methods are labor intensive and costly to perform on large volumes of pipe. Direct disposal does not take advantage of recycling, which could provide monetary dividends. To facilitate the decontamination and characterization of large-bore piping and thereby reduce the volume of piping required for disposal, a detailed analysis will be conducted to document the pipe remediation problem set; determine potential technologies to solve this remediation problem set; design and laboratory test potential decontamination and characterization technologies; fabricate a prototype system; provide a cost-benefit analysis of the proposed system; and transfer the technology to industry. This report summarizes the activities performed during fiscal year 1997 and describes the planned activities for fiscal year 1998. Accomplishments for FY97 include the development of the applicable and relevant and appropriate regulations, the screening of decontamination and characterization technologies, and the selection and initial design of the decontamination system.

  15. Large number discrimination by mosquitofish.

    Directory of Open Access Journals (Sweden)

    Christian Agrillo

    Full Text Available BACKGROUND: Recent studies have demonstrated that fish display rudimentary numerical abilities similar to those observed in mammals and birds. The mechanisms underlying the discrimination of small quantities (<4 were recently investigated while, to date, no study has examined the discrimination of large numerosities in fish. METHODOLOGY/PRINCIPAL FINDINGS: Subjects were trained to discriminate between two sets of small geometric figures using social reinforcement. In the first experiment mosquitofish were required to discriminate 4 from 8 objects with or without experimental control of the continuous variables that co-vary with number (area, space, density, total luminance. Results showed that fish can use the sole numerical information to compare quantities but that they preferentially use cumulative surface area as a proxy of the number when this information is available. A second experiment investigated the influence of the total number of elements to discriminate large quantities. Fish proved to be able to discriminate up to 100 vs. 200 objects, without showing any significant decrease in accuracy compared with the 4 vs. 8 discrimination. The third experiment investigated the influence of the ratio between the numerosities. Performance was found to decrease when decreasing the numerical distance. Fish were able to discriminate numbers when ratios were 1:2 or 2:3 but not when the ratio was 3:4. The performance of a sample of undergraduate students, tested non-verbally using the same sets of stimuli, largely overlapped that of fish. CONCLUSIONS/SIGNIFICANCE: Fish are able to use pure numerical information when discriminating between quantities larger than 4 units. As observed in human and non-human primates, the numerical system of fish appears to have virtually no upper limit while the numerical ratio has a clear effect on performance. These similarities further reinforce the view of a common origin of non-verbal numerical systems in all

  16. Radiosurgery for Large Brain Metastases

    International Nuclear Information System (INIS)

    Purpose: To determine the efficacy and safety of radiosurgery in patients with large brain metastases treated with radiosurgery. Patients and Methods: Eighty patients with large brain metastases (>14 cm3) were treated with radiosurgery between 1998 and 2009. The mean age was 59 ± 11 years, and 49 (61.3%) were men. Neurologic symptoms were identified in 77 patients (96.3%), and 30 (37.5%) exhibited a dependent functional status. The primary disease was under control in 36 patients (45.0%), and 44 (55.0%) had a single lesion. The mean tumor volume was 22.4 ± 8.8 cm3, and the mean marginal dose prescribed was 13.8 ± 2.2 Gy. Results: The median survival time from radiosurgery was 7.9 months (95% confidence interval [CI], 5.343–10.46), and the 1-year survival rate was 39.2%. Functional improvement within 1–4 months or the maintenance of the initial independent status was observed in 48 (60.0%) and 20 (25.0%) patients after radiosurgery, respectively. Control of the primary disease, a marginal dose of ≥11 Gy, and a tumor volume ≥26 cm3 were significantly associated with overall survival (hazard ratio, 0.479; p = .018; 95% CI, 0.261–0.880; hazard ratio, 0.350; p = .004; 95% CI, 0.171–0.718; hazard ratio, 2.307; p = .006; 95% CI, 1.274–4.180, respectively). Unacceptable radiation-related toxicities (Radiation Toxicity Oncology Group central nervous system toxicity Grade 3, 4, and 5 in 7, 6, and 2 patients, respectively) developed in 15 patients (18.8%). Conclusion: Radiosurgery seems to have a comparable efficacy with surgery for large brain metastases. However, the rate of radiation-related toxicities after radiosurgery should be considered when deciding on a treatment modality.

  17. Large area and flexible electronics

    CERN Document Server

    Caironi, Mario

    2015-01-01

    From materials to applications, this ready reference covers the entire value chain from fundamentals via processing right up to devices, presenting different approaches to large-area electronics, thus enabling readers to compare materials, properties and performance.Divided into two parts, the first focuses on the materials used for the electronic functionality, covering organic and inorganic semiconductors, including vacuum and solution-processed metal-oxide semiconductors, nanomembranes and nanocrystals, as well as conductors and insulators. The second part reviews the devices and applicatio

  18. Large capacity magazines and homicide

    OpenAIRE

    Carlisle E. Moody

    2015-01-01

    Recent events have resulted in calls to ban large capacity magazines (LCMs) holding more than 10 rounds of ammunition. Using data from a Virginia data base of crime guns seized by police between 1993 and 2013, we find that the proportion of crime guns with LCMs declined after the 1994 Federal assault weapons ban and increased after the ban was lifted in 2004. However, we can find no evidence that LCMs increased either murder or gun murder, implying that the Federal LCM ban did not have the in...

  19. Large Shareholders and Corporate Control

    OpenAIRE

    1986-01-01

    In a corporation with many small owners, it may not pay any one of them to monitor the performance of the management. We explore a model in which the presence of a large minority shareholder provides a partial solution to this free-rider problem. The model sheds light on the following questions: Under what circumstances will we observe a tender offer as opposed to a proxy fight or an internal management shake-up? How strong are the forces pushing toward increasing concentration of ownership o...

  20. The Large Aperture GRB Observatory

    CERN Document Server

    Allard, D; Asorey, H; Barros, H; Bertou, X; Castillo, M; Chirinos, J M; De Castro, A; Flores, S; González, J; Berisso, M Gomez; Grajales, J; Guada, C; Day, W R Guevara; Ishitsuka, J; López, J A; Martínez, O; Melfo, A; Meza, E; Loza, P Miranda; Barbosa, E Moreno; Murrugarra, C; Núñez, L A; Ormachea, L J Otiniano; Pérez, G; Perez, Y; Ponce, E; Quispe, J; Quintero, C; Rivera, H; Rosales, M; Rovero, A C; Saavedra, O; Salazar, H; Tello, J C; Peralda, R Ticona; Varela, E; Velarde, A; Villaseñor, L; Wahl, D; Zamalloa, M A

    2009-01-01

    The Large Aperture GRB Observatory (LAGO) is aiming at the detection of the high energy (around 100 GeV) component of Gamma Ray Bursts, using the single particle technique in arrays of Water Cherenkov Detectors (WCD) in high mountain sites (Chacaltaya, Bolivia, 5300 m a.s.l., Pico Espejo, Venezuela, 4750 m a.s.l., Sierra Negra, Mexico, 4650 m a.s.l). WCD at high altitude offer a unique possibility of detecting low gamma fluxes in the 10 GeV - 1 TeV range. The status of the Observatory and data collected from 2007 to date will be presented.

  1. Japanese large-scale interferometers

    International Nuclear Information System (INIS)

    The objective of the TAMA 300 interferometer was to develop advanced technologies for kilometre scale interferometers and to observe gravitational wave events in nearby galaxies. It was designed as a power-recycled Fabry-Perot-Michelson interferometer and was intended as a step towards a final interferometer in Japan. The present successful status of TAMA is presented. TAMA forms a basis for LCGT (large-scale cryogenic gravitational wave telescope), a 3 km scale cryogenic interferometer to be built in the Kamioka mine in Japan, implementing cryogenic mirror techniques. The plan of LCGT is schematically described along with its associated R and D

  2. Quick Mining of Isomorphic Exact Large Patterns from Large Graphs

    KAUST Repository

    Almasri, Islam

    2014-12-01

    The applications of the sub graph isomorphism search are growing with the growing number of areas that model their systems using graphs or networks. Specifically, many biological systems, such as protein interaction networks, molecular structures and protein contact maps, are modeled as graphs. The sub graph isomorphism search is concerned with finding all sub graphs that are isomorphic to a relevant query graph, the existence of such sub graphs can reflect on the characteristics of the modeled system. The most computationally expensive step in the search for isomorphic sub graphs is the backtracking algorithm that traverses the nodes of the target graph. In this paper, we propose a pruning approach that is inspired by the minimum remaining value heuristic that achieves greater scalability over large query and target graphs. Our testing on various biological networks shows that performance enhancement of our approach over existing state-of-the-art approaches varies between 6x and 53x. © 2014 IEEE.

  3. Electron Collisions with Large Molecules

    Science.gov (United States)

    McKoy, Vincent

    2006-10-01

    In recent years, interest in electron-molecule collisions has increasingly shifted to large molecules. Applications within the semiconductor industry, for example, require electron collision data for molecules such as perfluorocyclobutane, while almost all biological applications involve macromolecules such as DNA. A significant development in recent years has been the realization that slow electrons can directly damage DNA. This discovery has spurred studies of low-energy collisions with the constituents of DNA, including the bases, deoxyribose, the phosphate, and larger moieties assembled from them. In semiconductor applications, a key goal is development of electron cross section sets for plasma chemistry modeling, while biological studies are largely focused on understanding the role of localized resonances in inducing DNA strand breaks. Accurate calculations of low-energy electron collisions with polyatomic molecules are computationally demanding because of the low symmetry and inherent many-electron nature of the problem; moreover, the computational requirements scale rapidly with the size of the molecule. To pursue such studies, we have adapted our computational procedure, known as the Schwinger multichannel method, to run efficiently on highly parallel computers. In this talk, we will present some of our recent results for fluorocarbon etchants used in the semiconductor industry and for constituents of DNA and RNA. In collaboration with Carl Winstead, California Institute of Technology.

  4. Creating Large Scale Database Servers

    International Nuclear Information System (INIS)

    The BaBar experiment at the Stanford Linear Accelerator Center (SLAC) is designed to perform a high precision investigation of the decays of the B-meson produced from electron-positron interactions. The experiment, started in May 1999, will generate approximately 300TB/year of data for 10 years. All of the data will reside in Objectivity databases accessible via the Advanced Multi-threaded Server (AMS). To date, over 70TB of data have been placed in Objectivity/DB, making it one of the largest databases in the world. Providing access to such a large quantity of data through a database server is a daunting task. A full-scale testbed environment had to be developed to tune various software parameters and a fundamental change had to occur in the AMS architecture to allow it to scale past several hundred terabytes of data. Additionally, several protocol extensions had to be implemented to provide practical access to large quantities of data. This paper will describe the design of the database and the changes that we needed to make in the AMS for scalability reasons and how the lessons we learned would be applicable to virtually any kind of database server seeking to operate in the Petabyte region

  5. Joints for large superconducting conductors

    International Nuclear Information System (INIS)

    Large fusion magnets call for high-current conductors (up to 60 kA). This has been achieved by the cable-in-conduit conductor concept. The connection of these conductors has to take into account several demanding boundary conditions: a large number of strands (around 1000), a low resistance at high current (1-2 nΩ), low losses in pulsed field operation, Nb3Sn heat treatment, helium tightness control, limited available space. A conceptual design was developed by the CEA, based on the connection of two separate twin boxes clamped together, according to the lap-joint concept. These boxes are machined out of an explosive bonding plate (jacket material/copper), and the electrical connection is achieved by tin-lead soldering of the facing copper soles. After qualification of the explosive bond and validation of the joint concept in the laboratory, the technology was transferred to the industry within the framework of the manufacture of the ITER Toroidal Field Model Coil (TFMC). In addition, three full-size joint samples (FSJS), relevant to different jacket materials and joining techniques, were manufactured by the industry and successfully tested in the SULTAN facility at CRPP, Villigen. The paper reports on the results of the laboratory tests, describes the transfer of technology to industry, and lastly presents some typical experimental results

  6. Large scale cluster computing workshop

    Energy Technology Data Exchange (ETDEWEB)

    Dane Skow; Alan Silverman

    2002-12-23

    Recent revolutions in computer hardware and software technologies have paved the way for the large-scale deployment of clusters of commodity computers to address problems heretofore the domain of tightly coupled SMP processors. Near term projects within High Energy Physics and other computing communities will deploy clusters of scale 1000s of processors and be used by 100s to 1000s of independent users. This will expand the reach in both dimensions by an order of magnitude from the current successful production facilities. The goals of this workshop were: (1) to determine what tools exist which can scale up to the cluster sizes foreseen for the next generation of HENP experiments (several thousand nodes) and by implication to identify areas where some investment of money or effort is likely to be needed. (2) To compare and record experimences gained with such tools. (3) To produce a practical guide to all stages of planning, installing, building and operating a large computing cluster in HENP. (4) To identify and connect groups with similar interest within HENP and the larger clustering community.

  7. Quantum chromodynamics at large distances

    International Nuclear Information System (INIS)

    The properties of quantum chromodynamics (QCD)at large distances are considered in the framework of traditional quantum field theory. The parameters that determine the infrared region are determined self-consistently by means of the renormalization-group method. Recent studies that confirm a singular infrared asymptotic behavior M2 /(k2 )2 of the gluon propagator are reviewed. Solutions of the Schwinger--Dyson equation for the quark propagator are found with the necessary properties: spontaneous breaking of the chiral invariance and a nonperturbative nature. The infrared behaviors of the lowest Green's functions are used to calculate the vacuum expectation values of the gluon and quark fields. Good agreement between the calculated vacuum expectation values and their phenomenological values is obtained. The study of the behavior of QCD at large distances leads to the conclusion that at the present level of development of the theory two possibilities can be discussed. The first is the well-known confinement hypothesis; the second has been called incomplete confinement and necessarily implies that open color can be observed. It is shown that the second possibility does not contradict existing experiments. Experimental data on anomalous nuclear fragments and ultra-high-energy radiation from the galactic source Cygnus X-3 are considered as evidence for incomplete confinement. The importance of searches for states with open color is emphasized

  8. Large-mode enhancement cavities.

    Science.gov (United States)

    Carstens, Henning; Holzberger, Simon; Kaster, Jan; Weitenberg, Johannes; Pervak, Volodymyr; Apolonski, Alexander; Fill, Ernst; Krausz, Ferenc; Pupeza, Ioachim

    2013-05-01

    In passive enhancement cavities the achievable power level is limited by mirror damage. Here, we address the design of robust optical resonators with large spot sizes on all mirrors, a measure that promises to mitigate this limitation by decreasing both the intensity and the thermal gradient on the mirror surfaces. We introduce a misalignment sensitivity metric to evaluate the robustness of resonator designs. We identify the standard bow-tie resonator operated close to the inner stability edge as the most robust large-mode cavity and implement this cavity with two spherical mirrors with 600 mm radius of curvature, two plane mirrors and a round trip length of 1.2 m, demonstrating a stable power enhancement of near-infrared laser light by a factor of 2000. Beam radii of 5.7 mm × 2.6 mm (sagittal × tangential 1/e(2) intensity radius) on all mirrors are obtained. We propose a simple all-reflective ellipticity compensation scheme. This will enable a significant increase of the attainable power and intensity levels in enhancement cavities. PMID:23670017

  9. Global large carnivore conservation and international law

    NARCIS (Netherlands)

    Trouwborst, A.

    2015-01-01

    International cooperation, including through international legal instruments, appears important for the conservation of large carnivores worldwide. This is due to, inter alia, the worrying conservation status and population trends of many large carnivore species; the importance of large carnivores f

  10. Large-scale river regulation

    International Nuclear Information System (INIS)

    Recent concern over human impacts on the environment has tended to focus on climatic change, desertification, destruction of tropical rain forests, and pollution. Yet large-scale water projects such as dams, reservoirs, and inter-basin transfers are among the most dramatic and extensive ways in which our environment has been, and continues to be, transformed by human action. Water running to the sea is perceived as a lost resource, floods are viewed as major hazards, and wetlands are seen as wastelands. River regulation, involving the redistribution of water in time and space, is a key concept in socio-economic development. To achieve water and food security, to develop drylands, and to prevent desertification and drought are primary aims for many countries. A second key concept is ecological sustainability. Yet the ecology of rivers and their floodplains is dependent on the natural hydrological regime, and its related biochemical and geomorphological dynamics. (Author)

  11. Analysis of large urban fires

    International Nuclear Information System (INIS)

    Fires in urban areas caused by a nuclear burst are analyzed as a first step towards determining their smoke-generation chacteristics, which may have grave implications for global-scale climatic consequences. A chain of events and their component processes which would follow a nuclear attack are described. A numerical code is currently being developed to calculate ultimately the smoke production rate for a given attack scenario. Available models for most of the processes are incorporated into the code. Sample calculations of urban fire-development history performed in the code for an idealized uniform city are presented. Preliminary results indicate the importance of the wind, thermal radiation transmission, fuel distributions, and ignition thresholds on the urban fire spread characteristics. Future plans are to improve the existing models and develop new ones to characterize smoke production from large urban fires. 21 references, 18 figures

  12. Model of large pool fires

    International Nuclear Information System (INIS)

    A two zone entrainment model of pool fires is proposed to depict the fluid flow and flame properties of the fire. Consisting of combustion and plume zones, it provides a consistent scheme for developing non-dimensional scaling parameters for correlating and extrapolating pool fire visible flame length, flame tilt, surface emissive power, and fuel evaporation rate. The model is extended to include grey gas thermal radiation from soot particles in the flame zone, accounting for emission and absorption in both optically thin and thick regions. A model of convective heat transfer from the combustion zone to the liquid fuel pool, and from a water substrate to cryogenic fuel pools spreading on water, provides evaporation rates for both adiabatic and non-adiabatic fires. The model is tested against field measurements of large scale pool fires, principally of LNG, and is generally in agreement with experimental values of all variables

  13. Testing gravity on Large Scales

    Directory of Open Access Journals (Sweden)

    Raccanelli Alvise

    2013-09-01

    Full Text Available We show how it is possible to test general relativity and different models of gravity via Redshift-Space Distortions using forthcoming cosmological galaxy surveys. However, the theoretical models currently used to interpret the data often rely on simplifications that make them not accurate enough for precise measurements. We will discuss improvements to the theoretical modeling at very large scales, including wide-angle and general relativistic corrections; we then show that for wide and deep surveys those corrections need to be taken into account if we want to measure the growth of structures at a few percent level, and so perform tests on gravity, without introducing systematic errors. Finally, we report the results of some recent cosmological model tests carried out using those precise models.

  14. Author Clustering on Large Bibliographies

    CERN Document Server

    Sterz, Christoph

    2014-01-01

    We analyze and design an algorithm for clustering large sets of authors in Bibliographies. Not considering a distance function for a mutual comparison, but transforming the data into a multidimensional metric space, the algorithm described is similar to locally sensitive hashing. The task lies in the field of Record-Linkage. The algorithm was designed and performed based on the data of the CERN Document Server, consisting out of more than 1.7 million metadata entries and is part of the digital assets-managing-software invenio. Meant as a prototype, the algorithm performs efficiently, clustering all authors on CDS in under 30 minutes. We will discuss extensions improving the recall rate, wich still remains inferior to the currently used clustering-approach.

  15. Great expectations: large wind turbines

    International Nuclear Information System (INIS)

    This article focuses on wind turbine product development, and traces the background to wind turbines from the first generation 1.5 MW machines in 1995-6, plans for the second generation 3-5 MW class turbines to meet the expected boom in offshore wind projects, to the anticipated installation of a 4.5 MW turbine, and offshore wind projects planned for 2000-2002. The switch by the market leader Vestas to variable speed operation in 2000, the new product development and marketing strategy taken by the German Pro + Pro consultancy in their design of a 1.5 MW variable speed pitch control concept, the possible limiting of the size of turbines due to logistical difficulties, opportunities offered by air ships for large turbines, and the commissioning of offshore wind farms are discussed. Details of some 2-5 MW offshore wind turbine design specifications are tabulated

  16. Multipole correction in large synchrotrons

    International Nuclear Information System (INIS)

    A new method of correcting dynamic nonlinearities due to the multipole content of a synchrotron such as the Superconducting Super Collider is discussed. The method uses lumped multipole elements placed at the center (C) of the accelerator half-cells as well as elements near the focusing (F) and defocusing (D) quads. In a first approximation, the corrector strengths follow Simpson's Rule. Correction of second-order sextupole nonlinearities may also be obtained with the F, C, and D octupoles. Correction of nonlinearities by about three orders of magnitude are obtained, and simple solutions to a fundamental problem in synchrotrons are demonstrated. Applications to the CERN Large Hadron Collider and lower energy machines, as well as extensions for quadrupole correction, are also discussed

  17. Large area mercuric iodide photodetectors

    International Nuclear Information System (INIS)

    Results of an investigation of large area mercuric iodide (HgI2) photodetectors are reported. Different entrance contacts were studied, including semitransparent metallic films and conductive liquids. Theoretical calculations of electronic noise of these photodetectors were compared with experimental results. HgI2 photodetectors with active area up to 4 cm2 were matched with NaI(Tl) and CsI(Tl) scintillation crystals and were evaluated as gamma-radiation spectrometers. Energy resolution of 9.3% for gamma radiation of 511 keV with a CsI(Tl) scintillator and energy resolution of 9.0% for gamma radiation of 622 keV with a NaI(Tl) scintillator have been obtained

  18. Large area mercuric iodide photodetectors

    Energy Technology Data Exchange (ETDEWEB)

    Iwanczyk, J.S.; Dabrowski, A.J.; Markakis, J.M.; Ortale, C.; Schnepple, W.F.

    1984-02-01

    Results of an investigation of large area mercuric iodide (HgI/sub 2/) photodetectors are reported. Different entrance contacts were studied, including semitransparent metallic films and conductive liquids. Theoretical calculations of electronic noise of these photodetectors were compared with experimental results. HgI/sub 2/ photodetectors with active area up to 4 cm/sup 2/ were matched with NaI(Tl) and CsI(Tl) scintillation crystals and were evaluated as gamma-radiation spectrometers. Energy resolution of 9.3% for gamma radiation of 511 keV with a CsI(Tl) scintillator and energy resolution of 9.0% for gamma radiation of 622 keV with a NaI(Tl) scintillator have been obtained.

  19. Intergalactic shells at large redshift

    Science.gov (United States)

    Shull, J. M.; Silk, J.

    1981-01-01

    The intergalactic shells produced by galactic explosions at large redshift, whose interiors cool by inverse Compton scattering off the cosmic background radiation, have a characteristic angular size of about 1 arcmin at peak brightness. At z values lower than 2, the shells typically have a radius of 0.5 Mpc, a velocity of about 50 km/sec, a metal abundance of about 0.0001 of cosmic values, and strong radiation in H I(Lyman-alpha), He II 304 A, and the IR fine-structure lines of C II and Si II. The predicted extragalactic background emission from many shells, strongly peaked toward the UV, sets an upper limit to the number of exploding sources at z values of about 10. Shell absorption lines of H I, C II, Si II, and Fe II, which may be seen at more recent epochs in quasar spectra, may probe otherwise invisible explosions in the early universe.

  20. LARGE BLOCK TEST STATUS REPORT

    International Nuclear Information System (INIS)

    This report is intended to serve as a status report, which essentially transmits the data that have been collected to date on the Large Block Test (LBT). The analyses of data will be performed during FY98, and then a complete report will be prepared. This status report includes introductory material that is not needed merely to transmit data but is available at this time and therefore included. As such, this status report will serve as the template for the future report, and the information is thus preserved. The United States Department of Energy (DOE) is investigatinq the suitability of Yucca Mountain (YM) as a potential site for the nation's first high-level nuclear waste repository. As shown in Fig. 1-1, the site is located about 120 km northwest of Las Vegas, Nevada, in an area of uninhabited desert

  1. Large errors and severe conditions

    CERN Document Server

    Smith, D L; Van Wormer, L A

    2002-01-01

    Physical parameters that can assume real-number values over a continuous range are generally represented by inherently positive random variables. However, if the uncertainties in these parameters are significant (large errors), conventional means of representing and manipulating the associated variables can lead to erroneous results. Instead, all analyses involving them must be conducted in a probabilistic framework. Several issues must be considered: First, non-linear functional relations between primary and derived variables may lead to significant 'error amplification' (severe conditions). Second, the commonly used normal (Gaussian) probability distribution must be replaced by a more appropriate function that avoids the occurrence of negative sampling results. Third, both primary random variables and those derived through well-defined functions must be dealt with entirely in terms of their probability distributions. Parameter 'values' and 'errors' should be interpreted as specific moments of these probabil...

  2. Large Aperture Electrostatic Dust Detector

    International Nuclear Information System (INIS)

    Diagnosis and management of dust inventories generated in next-step magnetic fusion devices is necessary for their safe operation. A novel electrostatic dust detector, based on a fine grid of interlocking circuit traces biased to 30 or 50 v has been developed for the detection of dust particles on remote surfaces in air and vacuum environments. Impinging dust particles create a temporary short circuit and the resulting current pulse is recorded by counting electronics. Up to 90% of the particles are ejected from the grid or vaporized suggesting the device may be useful for controlling dust inventories. We report measurements of the sensitivity of a large area (5x5 cm) detector to microgram quantities of dust particles and review its applications to contemporary tokamaks and ITER.

  3. Adaptive Optics for Large Telescopes

    International Nuclear Information System (INIS)

    The use of adaptive optics was originally conceived by astronomers seeking to correct the blurring of images made with large telescopes due to the effects of atmospheric turbulence. The basic idea is to use a device, a wave front corrector, to adjust the phase of light passing through an optical system, based on some measurement of the spatial variation of the phase transverse to the light propagation direction, using a wave front sensor. Although the original concept was intended for application to astronomical imaging, the technique can be more generally applied. For instance, adaptive optics systems have been used for several decades to correct for aberrations in high-power laser systems. At Lawrence Livermore National Laboratory (LLNL), the world's largest laser system, the National Ignition Facility, uses adaptive optics to correct for aberrations in each of the 192 beams, all of which must be precisely focused on a millimeter scale target in order to perform nuclear physics experiments

  4. Large Eddy Simulations in Astrophysics

    CERN Document Server

    Schmidt, Wolfram

    2014-01-01

    In this review, the methodology of large eddy simulations (LES) is introduced and applications in astrophysics are discussed. As theoretical framework, the scale decomposition of the dynamical equations for neutral fluids by means of spatial filtering is explained. For cosmological applications, the filtered equations in comoving coordinates are also presented. To obtain a closed set of equations that can be evolved in LES, several subgrid scale models for the interactions between numerically resolved and unresolved scales are discussed, in particular the subgrid scale turbulence energy equation model. It is then shown how model coefficients can be calculated, either by dynamical procedures or, a priori, from high-resolution data. For astrophysical applications, adaptive mesh refinement is often indispensable. It is shown that the subgrid scale turbulence energy model allows for a particularly elegant and physically well motivated way of preserving momentum and energy conservation in AMR simulations. Moreover...

  5. Conference on Large Scale Optimization

    CERN Document Server

    Hearn, D; Pardalos, P

    1994-01-01

    On February 15-17, 1993, a conference on Large Scale Optimization, hosted by the Center for Applied Optimization, was held at the University of Florida. The con­ ference was supported by the National Science Foundation, the U. S. Army Research Office, and the University of Florida, with endorsements from SIAM, MPS, ORSA and IMACS. Forty one invited speakers presented papers on mathematical program­ ming and optimal control topics with an emphasis on algorithm development, real world applications and numerical results. Participants from Canada, Japan, Sweden, The Netherlands, Germany, Belgium, Greece, and Denmark gave the meeting an important international component. At­ tendees also included representatives from IBM, American Airlines, US Air, United Parcel Serice, AT & T Bell Labs, Thinking Machines, Army High Performance Com­ puting Research Center, and Argonne National Laboratory. In addition, the NSF sponsored attendance of thirteen graduate students from universities in the United States and abro...

  6. Adaptive Optics for Large Telescopes

    Energy Technology Data Exchange (ETDEWEB)

    Olivier, S

    2008-06-27

    The use of adaptive optics was originally conceived by astronomers seeking to correct the blurring of images made with large telescopes due to the effects of atmospheric turbulence. The basic idea is to use a device, a wave front corrector, to adjust the phase of light passing through an optical system, based on some measurement of the spatial variation of the phase transverse to the light propagation direction, using a wave front sensor. Although the original concept was intended for application to astronomical imaging, the technique can be more generally applied. For instance, adaptive optics systems have been used for several decades to correct for aberrations in high-power laser systems. At Lawrence Livermore National Laboratory (LLNL), the world's largest laser system, the National Ignition Facility, uses adaptive optics to correct for aberrations in each of the 192 beams, all of which must be precisely focused on a millimeter scale target in order to perform nuclear physics experiments.

  7. Large-scale solar heating

    Energy Technology Data Exchange (ETDEWEB)

    Tolonen, J.; Konttinen, P.; Lund, P. [Helsinki Univ. of Technology, Otaniemi (Finland). Advanced Energy Systems

    1998-10-01

    Solar heating market is growing in many European countries and annually installed collector area has exceeded one million square meters. There are dozens of collector manufacturers and hundreds of firms making solar heating installations in Europe. One tendency in solar heating is towards larger systems. These can be roof integrated, consisting of some tens or hundreds of square meters of collectors, or they can be larger centralized solar district heating plants consisting of a few thousand square meters of collectors. The increase of size can reduce the specific investments of solar heating systems, because e.g. the costs of some components (controllers, pumps, and pipes), planning and installation can be smaller in larger systems. The solar heat output can also be higher in large systems, because more advanced technique is economically viable

  8. Biotherapies in large vessel vasculitis.

    Science.gov (United States)

    Ferfar, Y; Mirault, T; Desbois, A C; Comarmond, C; Messas, E; Savey, L; Domont, F; Cacoub, P; Saadoun, D

    2016-06-01

    Giant cell arteritis (GCA) and Takayasu's arteritis (TA) are large vessel vasculitis (LVV) and aortic involvement is not uncommon in Behcet's disease (BD) and relapsing polychondritis (RP). Glucocorticosteroids are the mainstay of therapy in LVV. However, a significant proportion of patients have glucocorticoid dependance, serious side effects or refractory disease to steroids and other immunosuppressive treatments such as cyclophosphamide, azathioprine, mycophenolate mofetil and methotrexate. Recent advances in the understanding of the pathogenesis have resulted in the use of biological agents in patients with LVV. Anti-tumor necrosis factor-α drugs seem effective in patients with refractory Takayasu arteritis and vascular BD but have failed to do so in giant cell arteritis. Preliminary reports on the use of the anti-IL6-receptor antibody (tocilizumab), in LVV have been encouraging. The development of new biologic targeted therapies will probably open a promising future for patients with LVV. PMID:26883459

  9. Large-Scale Information Systems

    Energy Technology Data Exchange (ETDEWEB)

    D. M. Nicol; H. R. Ammerlahn; M. E. Goldsby; M. M. Johnson; D. E. Rhodes; A. S. Yoshimura

    2000-12-01

    Large enterprises are ever more dependent on their Large-Scale Information Systems (LSLS), computer systems that are distinguished architecturally by distributed components--data sources, networks, computing engines, simulations, human-in-the-loop control and remote access stations. These systems provide such capabilities as workflow, data fusion and distributed database access. The Nuclear Weapons Complex (NWC) contains many examples of LSIS components, a fact that motivates this research. However, most LSIS in use grew up from collections of separate subsystems that were not designed to be components of an integrated system. For this reason, they are often difficult to analyze and control. The problem is made more difficult by the size of a typical system, its diversity of information sources, and the institutional complexities associated with its geographic distribution across the enterprise. Moreover, there is no integrated approach for analyzing or managing such systems. Indeed, integrated development of LSIS is an active area of academic research. This work developed such an approach by simulating the various components of the LSIS and allowing the simulated components to interact with real LSIS subsystems. This research demonstrated two benefits. First, applying it to a particular LSIS provided a thorough understanding of the interfaces between the system's components. Second, it demonstrated how more rapid and detailed answers could be obtained to questions significant to the enterprise by interacting with the relevant LSIS subsystems through simulated components designed with those questions in mind. In a final, added phase of the project, investigations were made on extending this research to wireless communication networks in support of telemetry applications.

  10. The stellar scintillation on large and extremely large telescopes

    CERN Document Server

    Kornilov, Victor

    2012-01-01

    The accuracy of ground-based astronomical photometry is limited by two factors: photon statistics and stellar scintillation arising when star light passes through Earth's atmosphere. This paper examines the theoretical role of the outer scale $L_0$ of the optical turbulence (OT) which suppresses the low-frequency component of scintillation. It is shown that for typical values of $L_0 \\sim 25 - 50$ m, this effect becomes noticeable for a telescopes of diameter around 4 m. On extremely large, $30 - 40$ m, telescopes with exposures longer than a few seconds, the inclusion of the outer scale in the calculation reduces the scintillation power by more than a factor of 10 relative to conventional estimates. The details of this phenomenon are discussed for various models of non-Kolmogorov turbulence. Also, a quantitative description of the influence of the telescope central obscuration on the measured scintillation noise is introduced and combined with the effect of the outer scale. Evaluation of the scintillation no...

  11. Large Block Test Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Lin, W

    2001-12-01

    This report documents the Large-Block Test (LBT) conducted at Fran Ridge near Yucca Mountain, Nevada. The LBT was a thermal test conducted on an exposed block of middle non-lithophysal Topopah Spring tuff (Tptpmn) and was designed to assist in understanding the thermal-hydrological-mechanical-chemical (THMC) processes associated with heating and then cooling a partially saturated fractured rock mass. The LBT was unique in that it was a large (3 x 3 x 4.5 m) block with top and sides exposed. Because the block was exposed at the surface, boundary conditions on five of the six sides of the block were relatively well known and controlled, making this test both easier to model and easier to monitor. This report presents a detailed description of the test as well as analyses of the data and conclusions drawn from the test. The rock block that was tested during the LBT was exposed by excavation and removal of the surrounding rock. The block was characterized and instrumented, and the sides were sealed and insulated to inhibit moisture and heat loss. Temperature on the top of the block was also controlled. The block was heated for 13 months, during which time temperature, moisture distribution, and deformation were monitored. After the test was completed and the block cooled down, a series of boreholes were drilled, and one of the heater holes was over-cored to collect samples for post-test characterization of mineralogy and mechanical properties. Section 2 provides background on the test. Section 3 lists the test objectives and describes the block site, the site configuration, and measurements made during the test. Section 3 also presents a chronology of events associated with the LBT, characterization of the block, and the pre-heat analyses of the test. Section 4 describes the fracture network contained in the block. Section 5 describes the heating/cooling system used to control the temperature in the block and presents the thermal history of the block during the test

  12. Reviving large-scale projects

    International Nuclear Information System (INIS)

    For the past decade, most large-scale hydro development projects in northern Quebec have been put on hold due to land disputes with First Nations. Hydroelectric projects have recently been revived following an agreement signed with Aboriginal communities in the province who recognized the need to find new sources of revenue for future generations. Many Cree are working on the project to harness the waters of the Eastmain River located in the middle of their territory. The work involves building an 890 foot long dam, 30 dikes enclosing a 603 square-km reservoir, a spillway, and a power house with 3 generating units with a total capacity of 480 MW of power for start-up in 2007. The project will require the use of 2,400 workers in total. The Cree Construction and Development Company is working on relations between Quebec's 14,000 Crees and the James Bay Energy Corporation, the subsidiary of Hydro-Quebec which is developing the project. Approximately 10 per cent of the $735-million project has been designated for the environmental component. Inspectors ensure that the project complies fully with environmental protection guidelines. Total development costs for Eastmain-1 are in the order of $2 billion of which $735 million will cover work on site and the remainder will cover generating units, transportation and financial charges. Under the treaty known as the Peace of the Braves, signed in February 2002, the Quebec government and Hydro-Quebec will pay the Cree $70 million annually for 50 years for the right to exploit hydro, mining and forest resources within their territory. The project comes at a time when electricity export volumes to the New England states are down due to growth in Quebec's domestic demand. Hydropower is a renewable and non-polluting source of energy that is one of the most acceptable forms of energy where the Kyoto Protocol is concerned. It was emphasized that large-scale hydro-electric projects are needed to provide sufficient energy to meet both

  13. Joint studies on large CANDU

    International Nuclear Information System (INIS)

    from economic, safety and strategic viewpoints. A large number of research and development programs are now in place at AECL and KAERI that will permit substantial improvements to be realized in the next generation of CANDU okabts, Furthermore, opportunities exist for engineered improvements based on the research and development in advancing the generic CANDU Technology. Final Large CANDU joint study report with technical deliverables will be issued 1994 October. Phase 2 R and D program of the joint studies will be determined this year and implemented in next year. CANDU neutron economy permits versatility in choices of fuel cycles. This allows a utility to choose fuel cycle options for lower fuelling cost, better security of supply, and ultimately for much lower spent-fuel volume, than with PWR's alone. To meet Korea's strategic requirements, CANDU should be an integral part of the electricity supply mix.

  14. Anthropogenic Triggering of Large Earthquakes

    Science.gov (United States)

    Mulargia, Francesco; Bizzarri, Andrea

    2014-08-01

    The physical mechanism of the anthropogenic triggering of large earthquakes on active faults is studied on the basis of experimental phenomenology, i.e., that earthquakes occur on active tectonic faults, that crustal stress values are those measured in situ and, on active faults, comply to the values of the stress drop measured for real earthquakes, that the static friction coefficients are those inferred on faults, and that the effective triggering stresses are those inferred for real earthquakes. Deriving the conditions for earthquake nucleation as a time-dependent solution of the Tresca-Von Mises criterion applied in the framework of poroelasticity yields that active faults can be triggered by fluid overpressures < 0.1 MPa. Comparing this with the deviatoric stresses at the depth of crustal hypocenters, which are of the order of 1-10 MPa, we find that injecting in the subsoil fluids at the pressures typical of oil and gas production and storage may trigger destructive earthquakes on active faults at a few tens of kilometers. Fluid pressure propagates as slow stress waves along geometric paths operating in a drained condition and can advance the natural occurrence of earthquakes by a substantial amount of time. Furthermore, it is illusory to control earthquake triggering by close monitoring of minor ``foreshocks'', since the induction may occur with a delay up to several years.

  15. Large cities are less green

    CERN Document Server

    Oliveira, E A; Makse, H A

    2014-01-01

    We study how urban quality evolves as a result of carbon dioxide emissions as urban agglomerations grow. We employ a bottom-up approach combining two unprecedented microscopic data on population and carbon dioxide emissions in the continental US. We first aggregate settlements that are close to each other into cities using the City Clustering Algorithm (CCA) defining cities beyond the administrative boundaries. Then, we use data on $\\rm{CO}_2$ emissions at a fine geographic scale to determine the total emissions of each city. We find a superlinear scaling behavior, expressed by a power-law, between $\\rm{CO}_2$ emissions and city population with average allometric exponent $\\beta = 1.46$ across all cities in the US. This result suggests that the high productivity of large cities is done at the expense of a proportionally larger amount of emissions compared to small cities. Furthermore, our results are substantially different from those obtained by the standard administrative definition of cities, i.e. Metropol...

  16. [Pathogenesis of large vessel vasculitis].

    Science.gov (United States)

    Samson, M; Bonnotte, B

    2016-04-01

    Giant cell arteritis (GCA) and Takayasu's arteritis (TA) are two granulomatous vasculitis affecting large arteries that present specific epidemiological and clinical features. Their pathogenesis is not fully understood but major advances have been obtained during the last years, thus allowing the emergence of new therapeutic strategies. GCA and TA develop on a specific genetic background but share some similarities regarding the immunological pathways involved in their pathogenesis. The trigger of these diseases is not clearly identified but it is thought that an infectious agent could activate and lead to the maturation of dendritic cells that are localized in the adventitia of arteries. Then, the cells of the adaptative immune response are recruited and activated: CD4 T cells that polarize into Th1 and Th17 cells, cytotoxic CD8 T cells and Natural Killer cells. Furthermore, the T regulatory cells (Treg) are decreased both in GCA and TA. Humoral immune response seems also to be involved, especially in TA. Then, the cytokines produced by T lymphocytes (especially IL-17 and IFN-γ) trigger the recruitment and activation of monocytes and their differentiation into macrophages and multinuclear giant cells that produce IL-1β and IL-6 that are responsible for general symptoms of GCA and TA, and cytotoxic mediators and growth factors that trigger the remodeling of the arterial wall leading to aneurysms and ischemic manifestations of GCA an TA. PMID:26620872

  17. MALIGNANCY IN LARGE COLORECTAL LESIONS

    Directory of Open Access Journals (Sweden)

    Carlos Eduardo Oliveira dos SANTOS

    2014-09-01

    Full Text Available Context The size of colorectal lesions, besides a risk factor for malignancy, is a predictor for deeper invasion Objectives To evaluate the malignancy of colorectal lesions ≥20 mm. Methods Between 2007 and 2011, 76 neoplasms ≥20 mm in 70 patients were analyzed Results The mean age of the patients was 67.4 years, and 41 were women. Mean lesion size was 24.7 mm ± 6.2 mm (range: 20 to 50 mm. Half of the neoplasms were polypoid and the other half were non-polypoid. Forty-two (55.3% lesions were located in the left colon, and 34 in the right colon. There was a high prevalence of III L (39.5% and IV (53.9% pit patterns. There were 72 adenomas and 4 adenocarcinomas. Malignancy was observed in 5.3% of the lesions. Thirty-three lesions presented advanced histology (adenomas with high-grade dysplasia or early adenocarcinoma, with no difference in morphology and site. Only one lesion (1.3% invaded the submucosa. Lesions larger than 30 mm had advanced histology (P = 0.001. The primary treatment was endoscopic resection, and invasive carcinoma was referred to surgery. Recurrence rate was 10.6%. Conclusions Large colorectal neoplasms showed a low rate of malignancy. Endoscopic treatment is an effective therapy for these lesions.

  18. Disorder in large- N theories

    Science.gov (United States)

    Aharony, Ofer; Komargodski, Zohar; Yankielowicz, Shimon

    2016-04-01

    We consider Euclidean Conformal Field Theories perturbed by quenched disorder, namely by random fluctuations in their couplings. Such theories are relevant for second-order phase transitions in the presence of impurities or other forms of disorder. Theories with quenched disorder often flow to new fixed points of the renormalization group. We begin with disorder in free field theories. Imry and Ma showed that disordered free fields can only exist for d > 4. For d > 4 we show that disorder leads to new fixed points which are not scale-invariant. We then move on to large- N theories (vector models or gauge theories in the `t Hooft limit). We compute exactly the beta function for the disorder, and the correlation functions of the disordered theory. We generalize the results of Imry and Ma by showing that such disordered theories exist only when disorder couples to operators of dimension Δ > d/4. Sometimes the disordered fixed points are not scale-invariant, and in other cases they have unconventional dependence on the disorder, including non-trivial effects due to irrelevant operators. Holography maps disorder in conformal theories to stochastic differential equations in a higher dimensional space. We use this dictionary to reproduce our field theory results. We also study the leading 1 /N corrections, both by field theory methods and by holography. These corrections are particularly important when disorder scales with the number of degrees of freedom.

  19. Large errors and severe conditions

    International Nuclear Information System (INIS)

    Physical parameters that can assume real-number values over a continuous range are generally represented by inherently positive random variables. However, if the uncertainties in these parameters are significant (large errors), conventional means of representing and manipulating the associated variables can lead to erroneous results. Instead, all analyses involving them must be conducted in a probabilistic framework. Several issues must be considered: First, non-linear functional relations between primary and derived variables may lead to significant 'error amplification' (severe conditions). Second, the commonly used normal (Gaussian) probability distribution must be replaced by a more appropriate function that avoids the occurrence of negative sampling results. Third, both primary random variables and those derived through well-defined functions must be dealt with entirely in terms of their probability distributions. Parameter 'values' and 'errors' should be interpreted as specific moments of these probability distributions. Fourth, there are pragmatic reasons for seeking convenient analytical formulas to approximate the 'true' probability distributions of derived parameters generated by Monte Carlo simulation. This paper discusses each of these issues and illustrates the main concepts with realistic examples involving radioactivity decay and nuclear astrophysics

  20. Large HTGR control room design

    International Nuclear Information System (INIS)

    The standard HTGR control room arrangement is based on an extensive program that started with a study of human engineering principles and evolved with the use of a full-scale mock-up employed to arrive at an optimized control board layout and select proper components for the man-machine interface. The integrated control system makes extensive use of a dual computer as a tool for data collection, alarming, and formating information for the operator, using cathode ray tubes (CRTs) as the prime display. Window type annunciators, recorders, and large pistol-grip switches have been replaced by multicolor CRTs, line printers, and miniature pushbutton switches designed into a compact monitoring and control console. The console is designed for stand-up and sit-down operation and is shaped for maximum operator convenience. Indicators and controls are functionally arranged so the operator can easily scan, compare like parameters, and respond to abnormal conditions. A summary is presented of the features General Atomic has included in the HTGR control room design and of approaches used to develop a modern design that meets General Atomic's objectives as well as current regulatory and code requirements. (U.S.)

  1. Computing issues for large detectors

    International Nuclear Information System (INIS)

    The computing issues which will affect planning for experiments at RHIC is reviewed. It is traditional in workshops on new facilities to discuss the computing requirements for the experiments. Usually this discussion will focus on the number of MIPS (Million Instructions Per Second) needed to analyze the data tapes and, perhaps, the number of Terabytes of data storage. These are important parameters for planning new facilities. They are, however, only two of the features that define the computing requirements for new experiments. In this paper, the author discusses a broader range of computing issues and indicates how the problems of large experiments might be addressed on the time-scale of RHIC. In this discussion, he draws on the experiences of high energy physics groups working at colliding beam facilities, especially the Tevatron and LEP. In the colliding beam experiments, it has become increasingly important to consider the computing system as a component of the full detector system. The computing system includes online and offline computers, workstations, networks and mass-storage. It also includes software, both commercial and experiment-specific. In the next section, he reviews recent developments in computing equipment as well as mass storage and networks. In the following section, he turns to the problems of software development, testing and maintenance

  2. Mapping change in large networks.

    Directory of Open Access Journals (Sweden)

    Martin Rosvall

    Full Text Available Change is a fundamental ingredient of interaction patterns in biology, technology, the economy, and science itself: Interactions within and between organisms change; transportation patterns by air, land, and sea all change; the global financial flow changes; and the frontiers of scientific research change. Networks and clustering methods have become important tools to comprehend instances of these large-scale structures, but without methods to distinguish between real trends and noisy data, these approaches are not useful for studying how networks change. Only if we can assign significance to the partitioning of single networks can we distinguish meaningful structural changes from random fluctuations. Here we show that bootstrap resampling accompanied by significance clustering provides a solution to this problem. To connect changing structures with the changing function of networks, we highlight and summarize the significant structural changes with alluvial diagrams and realize de Solla Price's vision of mapping change in science: studying the citation pattern between about 7000 scientific journals over the past decade, we find that neuroscience has transformed from an interdisciplinary specialty to a mature and stand-alone discipline.

  3. Control of large space structures

    Science.gov (United States)

    Gran, R.; Rossi, M.; Moyer, H. G.; Austin, F.

    1979-01-01

    The control of large space structures was studied to determine what, if any, limitations are imposed on the size of spacecraft which may be controlled using current control system design technology. Using a typical structure in the 35 to 70 meter size category, a control system design that used actuators that are currently available was designed. The amount of control power required to maintain the vehicle in a stabilized gravity gradient pointing orientation that also damped various structural motions was determined. The moment of inertia and mass properties of this structure were varied to verify that stability and performance were maintained. The study concludes that the structure's size is required to change by at least a factor of two before any stability problems arise. The stability margin that is lost is due to the scaling of the gravity gradient torques (the rigid body control) and as such can easily be corrected by changing the control gains associated with the rigid body control. A secondary conclusion from the study is that the control design that accommodates the structural motions (to damp them) is a little more sensitive than the design that works on attitude control of the rigid body only.

  4. Shutdown problems in large tokamaks

    International Nuclear Information System (INIS)

    Some of the problems connected with a normal shutdown at the end of the burn phase (soft shutdown) and with a shutdown caused by disruptive instability (hard shutdown) have been considered. For a soft shutdown a cursory literature search was undertaken and methods for controlling the thermal wall loading were listed. Because shutdown computer codes are not widespread, some of the differences between start-up codes and shutdown codes were discussed along with program changes needed to change a start-up code to a shutdown code. For a hard shutdown, the major problems are large induced voltages in the ohmic-heating and equilibrium-field coils and high first wall erosion. A literature search of plasma-wall interactions was carried out. Phenomena that occur at the plasma-wall interface can be quite complicated. For example, material evaporated from the wall can form a virtual limiter or shield protecting the wall from major damage. Thermal gradients that occur during the interaction can produce currents whose associated magnetic field also helps shield the wall

  5. Chemotaxis of large granular lymphocytes

    International Nuclear Information System (INIS)

    The hypothesis that large granular lymphocytes (LGL) are capable of directed locomotion (chemotaxis) was tested. A population of LGL isolated from discontinuous Percoll gradients migrated along concentration gradients of N-formyl-methionyl-leucyl-phenylalanine (f-MLP), casein, and C5a, well known chemoattractants for polymorphonuclear leukocytes and monocytes, as well as interferon-β and colony-stimulating factor. Interleukin 2, tuftsin, platelet-derived growth factor, and fibronectin were inactive. Migratory responses were greater in Percoll fractions with the highest lytic activity and HNK-1+ cells. The chemotactic response to f-MLP, casein, and C5a was always greater when the chemoattractant was present in greater concentration in the lower compartment of the Boyden chamber. Optimum chemotaxis was observed after a 1 hr incubation that made use of 12 μm nitrocellulose filters. LGL exhibited a high degree of nondirected locomotion when allowed to migrate for longer periods (> 2 hr), and when cultured in vitro for 24 to 72 hr in the presence or absence of IL 2 containing phytohemagluttinin-conditioned medium. LGL chemotaxis to f-MLP could be inhibited in a dose-dependent manner by the inactive structural analog CBZ-phe-met, and the RNK tumor line specifically bound f-ML(3H)P, suggesting that LGL bear receptors for the chemotactic peptide

  6. Phase II Pediatric Study With Dabrafenib in HGG Patients

    Science.gov (United States)

    2016-03-09

    Anaplastic Astrocytoma; Glioblastoma; Giant Cell Glioblastoma; Gliosarcoma; Anaplastic Oligodendroglioma; Anaplastic Oligoastrocytoma; Anaplastic Ependymoma; Choroid Plexus Carcinoma; Anaplastic Ganglioglioma; Pineal Parenchymal Tumor; Pineoblastoma; Medulloblastoma; PNET; Rhabdoid Tumor; Perineurioma; MPNST; Malignant Meningloma; Anaplastic Hemangiopericytoma

  7. Large optics inspection, tilting, and washing stand

    Science.gov (United States)

    Ayers, Marion Jay; Ayers, Shannon Lee

    2012-10-09

    A large optics stand provides a risk free means of safely tilting large optics with ease and a method of safely tilting large optics with ease. The optics are supported in the horizontal position by pads. In the vertical plane the optics are supported by saddles that evenly distribute the optics weight over a large area.

  8. Large optics inspection, tilting, and washing stand

    Science.gov (United States)

    Ayers, Marion Jay; Ayers, Shannon Lee

    2010-08-24

    A large optics stand provides a risk free means of safely tilting large optics with ease and a method of safely tilting large optics with ease. The optics are supported in the horizontal position by pads. In the vertical plane the optics are supported by saddles that evenly distribute the optics weight over a large area.

  9. Fronts in Large Marine Ecosystems

    Science.gov (United States)

    Belkin, Igor M.; Cornillon, Peter C.; Sherman, Kenneth

    2009-04-01

    Oceanic fronts shape marine ecosystems; therefore front mapping and characterization are among the most important aspects of physical oceanography. Here we report on the first global remote sensing survey of fronts in the Large Marine Ecosystems (LME). This survey is based on a unique frontal data archive assembled at the University of Rhode Island. Thermal fronts were automatically derived with the edge detection algorithm of Cayula and Cornillon (1992, 1995, 1996) from 12 years of twice-daily, global, 9-km resolution satellite sea surface temperature (SST) fields to produce synoptic (nearly instantaneous) frontal maps, and to compute the long-term mean frequency of occurrence of SST fronts and their gradients. These synoptic and long-term maps were used to identify major quasi-stationary fronts and to derive provisional frontal distribution maps for all LMEs. Since SST fronts are typically collocated with fronts in other water properties such as salinity, density and chlorophyll, digital frontal paths from SST frontal maps can be used in studies of physical-biological correlations at fronts. Frontal patterns in several exemplary LMEs are described and compared, including those for: the East and West Bering Sea LMEs, Sea of Okhotsk LME, East China Sea LME, Yellow Sea LME, North Sea LME, East and West Greenland Shelf LMEs, Newfoundland-Labrador Shelf LME, Northeast and Southeast US Continental Shelf LMEs, Gulf of Mexico LME, and Patagonian Shelf LME. Seasonal evolution of frontal patterns in major upwelling zones reveals an order-of-magnitude growth of frontal scales from summer to winter. A classification of LMEs with regard to the origin and physics of their respective dominant fronts is presented. The proposed classification lends itself to comparative studies of frontal ecosystems.

  10. Large dams and risk management

    International Nuclear Information System (INIS)

    In July 1996, Quebec's Saguenay region was subjected to intensive rainfall which caused severe floods and uncontrolled release of several reservoirs, resulting in extensive damage to dam structures and reservoirs. The probability of occurrence for that disaster was 1:10,000. Following the disaster, the Quebec government established a dam management body entitled the Commission scientifique et technique sur la gestion des barrages, which pointed out several safety shortcomings of existing dams. Many were either very old or had undergone significant function change without being subsequently re-evaluated. A report by the Commission stated that damage following the floods could have been limited if the design and operating standards of the dams had been more stringent. A Dam Safety Act was adopted by the Quebec National Assembly on May 30, 2000 following recommendations to retain safer structures. The Act demands regular reporting of operating procedures. Seismic activity was noted as being a topic that requires in-depth examination since Quebec's St. Lawrence Valley, particularly the Charlevoix region, is one of Canada's largest seismic zones. The other is on the west coast in British Columbia. Earthquakes in Quebec are less intense than the ones in British Columbia, but they have higher frequency content which exerts a quasi-resonance wave effect which impacts roads, bridges, buildings and hydroelectric generating facilities. Hydro-Quebec is a public utility which owns 563 retaining structures, of which 228 are ranked as large dams that measure more than 15 metres high, 400 metres long and with a reservoir capacity of more than 1 million cubic metres of water. Hydro-Quebec addresses hydrological, seismic, technological and human risks through a dam safety procedure that includes structured plans for choosing best alternatives through staged exercises. Hazard levels are minimized through the adoption of emergency, prevention and alleviation measures. The utility

  11. Aeroelasticity of Large Wind Turbines

    Energy Technology Data Exchange (ETDEWEB)

    Holierhoek, J.G.

    2008-11-19

    The aeroelastic stability of wind turbines can be investigated by simulating models of the turbines under different conditions. Wind condition, pitch angle setting and rotational velocity will influence the aeroelastic stability. This dissertation describes the development and use of one fully nonlinear aeroelastic tool that has been developed especially for large wind turbines, but it can also be used for many other systems with bending and torsional degrees of freedom. This tool is called WOBBE. The calculations are performed using nonlinear dynamics and nonlinear aerodynamics. This is important, because linearising is always a somewhat arbitrary process where experience is used to determine which terms can and cannot be left out of the equations. The importance of performing fully nonlinear calculations will be shown by discussing the differences between the results from linear programmes and WOBBE. The combination of using linearised tools to investigate the possible problem areas and nonlinear tools to zoom in on these possible unstable conditions seems to be a logical approach of the aeroelastic analysis during the design. WOBBE simulates multi-body systems, where the rigid bodies are interconnected with hinges, springs and dampers. The aerodynamic forces acting on this system are calculated by the programme. The blade element momentum method is used for these calculations. The calculations of the motions are performed using Hamilton's generalised momenta and the generalised coordinates as state variables. WOBBE has been developed purely to perform simulations to determine the aeroelastic (in)stability of the system, not to determine the stresses in the components of the turbine. If there are any unknown or unexpected instabilities for the given setting, these will also show up in the simulation, as the method does not focus solely on expected instabilities. Next to the fact that WOBBE performs the simulations fully nonlinear, this is another advantage

  12. Handbook of Large-Scale Random Networks

    CERN Document Server

    Bollobas, Bela; Miklos, Dezso

    2008-01-01

    Covers various aspects of large-scale networks, including mathematical foundations and rigorous results of random graph theory, modeling and computational aspects of large-scale networks, as well as areas in physics, biology, neuroscience, sociology and technical areas

  13. Architecture of Large-Scale Systems

    OpenAIRE

    Koschel, Arne; Astrova, Irina; Deutschkämer, Elena; Ester, Jacob; Feldmann, Johannes

    2013-01-01

    In this paper various techniques in relation to large-scale systems are presented. At first, explanation of large-scale systems and differences from traditional systems are given. Next, possible specifications and requirements on hardware and software are listed. Finally, examples of large-scale systems are presented.

  14. 77 FR 18109 - Assessments, Large Bank Pricing

    Science.gov (United States)

    2012-03-27

    ..., significantly reduce reporting burden, and satisfy many concerns voiced by the banking industry. DATES: Comments...\\ Assessments, Large Bank Pricing, 76 FR 10672 (February 25, 2011) (to be codified at 12 CFR 327.9). \\4\\ A large... may also be adjusted by the large bank adjustment. 76 FR 10672, 10714 (February 25, 2011) (to...

  15. Large Devaluations and the Real Exchange Rate

    Science.gov (United States)

    Burstein, Ariel; Eichenbaum, Martin; Rebelo, Sergio

    2005-01-01

    In this paper we argue that the primary force behind the large drop in real exchange rates that occurs after large devaluations is the slow adjustment in the prices of nontradable goods and services. Our empirical analysis uses data from five large devaluation episodes: Argentina (2002), Brazil (1999), Korea (1997), Mexico (1994), and Thailand…

  16. 27 CFR 19.915 - Large plants.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Large plants. 19.915... OF THE TREASURY LIQUORS DISTILLED SPIRITS PLANTS Distilled Spirits For Fuel Use Permits § 19.915 Large plants. Any person wishing to establish a large plant shall make application for and obtain...

  17. Alternative large Nc baryons and holography

    International Nuclear Information System (INIS)

    In gauge theories in the limit of a large number Nc of colors baryons are usually described as heavy solitonic objects with mass of order Nc. We discuss an alternative large Nc description both directly in the field theory as well as using holography. In this alternative large Nc limit at least some of the baryons behave like mesons, that is they stay light even at large Nc and their interactions vanish in that limit. For Nc=3 these alternative large Nc baryons are equivalent to the standard baryons. In the holographic description it is manifest that the Regge slopes of mesons and alternative baryons are degenerate.

  18. Alternative large Nc baryons and holography

    CERN Document Server

    Hoyos-Badajoz, Carlos

    2009-01-01

    In gauge theories in the limit of a large number Nc of colors, baryons are usually described as heavy solitonic objects with mass of order Nc. We discuss an alternative large Nc description both directly in the field theory as well as using holography. In this alternative large Nc limit at least some of the baryons behave like mesons, that is they stay light even at large Nc and their interactions vanish in that limit. For Nc=3 these alternative large Nc baryons are equivalent to the standard baryons. In the holographic description it is manifest that the Regge slopes of mesons and alternative baryons are degenerate.

  19. Large Devaluations and the Real Exchange Rate

    OpenAIRE

    Ariel Burstein; Martin Eichenbaum; Sergio Rebelo

    2004-01-01

    In this Paper we argue that the primary force behind the large drop in real exchange rates that occurs after large devaluations is the slow adjustment in the price of non-tradable goods and services. Our empirical analysis uses data from five large devaluation episodes: Argentina (2001), Brazil (1999), Korea (1997), Mexico (1994), and Thailand (1997). We conduct a detailed analysis of the Argentina case using disaggregated CPI data, data from our own survey of prices in Buenos Aires, and scan...

  20. Small Price Responses to Large Demand Shocks

    OpenAIRE

    Gagnon, Etienne; Lopez-Salido, J. David

    2014-01-01

    We study the pricing response of U.S. supermarkets to large demand shocks triggered by labor conflicts, mass population relocation, and shopping sprees around major snowstorms and hurricanes. Our focus on demand shocks is novel in the empirical literature that uses large datasets of individual data to bridge micro price behavior and aggregate price dynamics. We find that large swings in demand have, at best, modest effects on the level of retail prices, consistent with flat short- to medium-t...

  1. Large proximal ureteral stones: Ideal treatment modality?

    OpenAIRE

    Kadyan, B.; V Sabale; D Mane; V Satav; A Mulay; Thakur, N.; Kankalia, S. P.

    2016-01-01

    Background and Purpose: Ideal treatment modality for patients with large impacted proximal ureteral stone remains controversial. We compared laparoscopic transperitoneal ureterolithotomy (Lap-TPUL) and semirigid ureteroscopy for large proximal ureteric stones to evaluate their efficacy and safety. Patients and Methods: From November 2012 to December 2014, we enrolled 122 patients with large (≥1.5 cm) proximal ureteral stone in the study. Patients were randomly divided into two groups: Group A...

  2. Large proximal ureteral stones: Ideal treatment modality?

    OpenAIRE

    Kadyan, B.; V Sabale; D Mane; V Satav; A Mulay; Thakur, N.; Kankalia, S. P.

    2016-01-01

    Background and Purpose: Ideal treatment modality for patients with large impacted proximal ureteral stone remains controversial. We compared laparoscopic transperitoneal ureterolithotomy (Lap-TPUL) and semirigid ureteroscopy for large proximal ureteric stones to evaluate their efficacy and safety. Patients and Methods: From November 2012 to December 2014, we enrolled 122 patients with large (≥1.5 cm) proximal ureteral stone in the study. Patients were randomly divided into two groups: Grou...

  3. Large transverse momentum behavior of gauge theories

    International Nuclear Information System (INIS)

    The large transverse momentum behavior of Compton scattering and Moeller scattering in Quantum Electrodynamics; and of elastic quark-quark scattering in Quantum Chromodynamics are examined in perturbation theory. The results strongly suggest that the large transverse momentum regime in gauge theories is governed by a differential equation of the Callan-Symanzik type with a suitable momentum dependent anomalous dimension term. An explicit solution for the quark-quark elastic scattering amplitude at large transverse momentum is given

  4. Shape control of large space structures

    Science.gov (United States)

    Hagan, M. T.

    1982-01-01

    A survey has been conducted to determine the types of control strategies which have been proposed for controlling the vibrations in large space structures. From this survey several representative control strategies were singled out for detailed analyses. The application of these strategies to a simplified model of a large space structure has been simulated. These simulations demonstrate the implementation of the control algorithms and provide a basis for a preliminary comparison of their suitability for large space structure control.

  5. ELID Grinding of Large Aspheric Optics Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Large aperture aspheric optics are among the most susceptible optical surfaces to the accumulation of periodic surface artifacts during fabrication. Periodic...

  6. Improved Large-Field Focusing Schlieren System

    Science.gov (United States)

    Weinstein, Leonard M.

    1993-01-01

    System used to examine complicated two- and three-dimensional flows. High-brightness large-field focusing schlieren system incorporates Fresnel lens instead of glass diffuser. In system with large field of view, image may also be very large. Relay optical subsystem minifies large image while retaining all of light. Facilities candidates for use of focusing schlieren include low-speed wind and water tunnels. Heated or cooled flow tracers or injected low- or high-density tracers used to make flows visible for photographic recording.

  7. Large scale numerical simulation for superfluid turbulence

    International Nuclear Information System (INIS)

    Large scale numerical simulation of quantum turbulence is performed by using 3-D time-dependent Gross-Pitaevskii equation. The energy spectrum obeying Kolmogorov law and large scale self-similar structure of quantum vortex tangle are found in a fully developed dumped turbulent state. We confirm that inertial range of the energy spectrum becomes large as the system size of the simulation becomes large that is consistent with the result of the normal fluid turbulence. On the other hand, bottleneck effect near coherent length prevents the inertial range from extending to smaller scale. (author)

  8. Reliability of large and complex systems

    CERN Document Server

    Kolowrocki, Krzysztof

    2014-01-01

    Reliability of Large and Complex Systems, previously titled Reliability of Large Systems, is an innovative guide to the current state and reliability of large and complex systems. In addition to revised and updated content on the complexity and safety of large and complex mechanisms, this new edition looks at the reliability of nanosystems, a key research topic in nanotechnology science. The author discusses the importance of safety investigation of critical infrastructures that have aged or have been exposed to varying operational conditions. This reference provides an asympt

  9. Large Format Uncooled Focal Plane Array Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Black Forest Engineering has identified innovative modifications in uncooled focal plane array (UFPA) architecture and processing that allows development of large...

  10. Computing in Large-Scale Dynamic Systems

    NARCIS (Netherlands)

    Pruteanu, A.S.

    2013-01-01

    Software applications developed for large-scale systems have always been difficult to de- velop due to problems caused by the large number of computing devices involved. Above a certain network size (roughly one hundred), necessary services such as code updating, topol- ogy discovery and data dissem

  11. Large- quantum chromodynamics and harmonic sums

    Indian Academy of Sciences (India)

    Eduardo De Rafael

    2012-06-01

    In the large- limit of QCD, two-point functions of local operators become harmonic sums. I review some properties which follow from this fact and which are relevant for phenomenological applications. This has led us to consider a class of analytic number theory functions as toy models of large- QCD which also is discussed.

  12. Hierarchies of Alarms for Large Distributed Systems

    CERN Document Server

    Boccioli, M; Martos, V; Holme, O

    2014-01-01

    The control systems of most of the infrastructure at CERN make use of the SCADA package WinCC Open Architecture by ETM*, including successful projects to control large scale systems such as the Large Hadron Collider (LHC) accelerator and associated experiments.).

  13. The algebras of large N matrix mechanics

    Energy Technology Data Exchange (ETDEWEB)

    Halpern, M.B.; Schwartz, C.

    1999-09-16

    Extending early work, we formulate the large N matrix mechanics of general bosonic, fermionic and supersymmetric matrix models, including Matrix theory: The Hamiltonian framework of large N matrix mechanics provides a natural setting in which to study the algebras of the large N limit, including (reduced) Lie algebras, (reduced) supersymmetry algebras and free algebras. We find in particular a broad array of new free algebras which we call symmetric Cuntz algebras, interacting symmetric Cuntz algebras, symmetric Bose/Fermi/Cuntz algebras and symmetric Cuntz superalgebras, and we discuss the role of these algebras in solving the large N theory. Most important, the interacting Cuntz algebras are associated to a set of new (hidden!) local quantities which are generically conserved only at large N. A number of other new large N phenomena are also observed, including the intrinsic nonlocality of the (reduced) trace class operators of the theory and a closely related large N field identification phenomenon which is associated to another set (this time nonlocal) of new conserved quantities at large N.

  14. Automating large-scale reactor systems

    Energy Technology Data Exchange (ETDEWEB)

    Kisner, R.A.

    1985-01-01

    This paper conveys a philosophy for developing automated large-scale control systems that behave in an integrated, intelligent, flexible manner. Methods for operating large-scale systems under varying degrees of equipment degradation are discussed, and a design approach that separates the effort into phases is suggested. 5 refs., 1 fig.

  15. Large Nonferrous Metals Deposits Found in Yunnan

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    <正>According to the Department of Land and Resources of Yunnan, Yunnan has made great achievements since implementation of the geological prospecting action plan. 5 ultra-large deposits and several large deposits have been found, and a group of key areas with favorable ore-forming prospect have been pinpointed.

  16. The large deviation approach to statistical mechanics

    Energy Technology Data Exchange (ETDEWEB)

    Touchette, Hugo [School of Mathematical Sciences, Queen Mary University of London, London E1 4NS (United Kingdom)], E-mail: h.touchette@qmul.ac.uk

    2009-07-15

    The theory of large deviations is concerned with the exponential decay of probabilities of large fluctuations in random systems. These probabilities are important in many fields of study, including statistics, finance, and engineering, as they often yield valuable information about the large fluctuations of a random system around its most probable state or trajectory. In the context of equilibrium statistical mechanics, the theory of large deviations provides exponential-order estimates of probabilities that refine and generalize Einstein's theory of fluctuations. This review explores this and other connections between large deviation theory and statistical mechanics, in an effort to show that the mathematical language of statistical mechanics is the language of large deviation theory. The first part of the review presents the basics of large deviation theory, and works out many of its classical applications related to sums of random variables and Markov processes. The second part goes through many problems and results of statistical mechanics, and shows how these can be formulated and derived within the context of large deviation theory. The problems and results treated cover a wide range of physical systems, including equilibrium many-particle systems, noise-perturbed dynamics, nonequilibrium systems, as well as multifractals, disordered systems, and chaotic systems. This review also covers many fundamental aspects of statistical mechanics, such as the derivation of variational principles characterizing equilibrium and nonequilibrium states, the breaking of the Legendre transform for nonconcave entropies, and the characterization of nonequilibrium fluctuations through fluctuation relations.

  17. Effects of combustible stacking in large compartments

    DEFF Research Database (Denmark)

    Gentili, Filippo; Giuliani, Luisa; Bontempi, Franco

    2013-01-01

    This paper focuses on the modelling of fire in case of various distributions of combustible materials in a large compartment. Large compartments often represent a challenge for structural fire safety, because of lack of prescriptive rules to follow and difficulties of taking into account the effect...

  18. ICTP lectures on large extra dimensions

    International Nuclear Information System (INIS)

    I give a brief and elementary introduction to braneworld models with large extra dimensions. Three conceptually distinct scenarios are outlined: (i) Large compact extra dimensions; (ii) Warped extra dimensions; (iii) Infinite volume extra dimensions. As an example I discuss in detail an application of (iii) to the late-time cosmology and acceleration problem of the Universe. (author)

  19. Large 1 behaviour of the phase shifts

    International Nuclear Information System (INIS)

    We investigate the large l behaviour of the phase-shifts, using their W.K.B. expressions, which are good in this case. A recurrence relation for the phase-shifts is deduced when the potentials fall off as 1/sub(r)m, while a potentially useful inequality is obtained for potentials which decrease monotonically for large r. (author)

  20. 75 FR 73983 - Assessments, Large Bank Pricing

    Science.gov (United States)

    2010-11-30

    ... Kapoor, Counsel, Legal Division, (202) 898-3960. Correction In proposed rule FR Doc. 2010-29138...; ] FEDERAL DEPOSIT INSURANCE CORPORATION 12 CFR Part 327 RIN 3064-AD66 Assessments, Large Bank Pricing AGENCY..., 2010, regarding Assessments, Large Bank Pricing. This correction clarifies that the comment period...

  1. 76 FR 17521 - Assessments, Large Bank Pricing

    Science.gov (United States)

    2011-03-30

    ... Register of February 25, 2011 (76 FR 10672), regarding Assessments, Large Bank Pricing. This correction... 17th Street, NW., Washington, DC 20429. SUPPLEMENTARY INFORMATION: In FR Doc. 2011-3086, appearing on... 327 RIN 3064-AD66 Assessments, Large Bank Pricing AGENCY: Federal Deposit Insurance Corporation...

  2. Implementing Large Projects in Software Engineering Courses

    Science.gov (United States)

    Coppit, David

    2006-01-01

    In software engineering education, large projects are widely recognized as a useful way of exposing students to the real-world difficulties of team software development. But large projects are difficult to put into practice. First, educators rarely have additional time to manage software projects. Second, classrooms have inherent limitations that…

  3. Integration of large scale wind power

    Energy Technology Data Exchange (ETDEWEB)

    Davidsen, Troels [Inopower A/S (Denmark)

    2011-07-01

    Since 2006, the Danish TSO Energinet.dk, has got large power consumption systems available for balancing the power grid during large Wind Power in feed situations. In 2011 a total of 250 MW electro boilers are installed. The power for the electro boilers is traded on the Nordpool power exchange in the day a head market and the ancillary services markets. (orig.)

  4. Automating large-scale reactor systems

    International Nuclear Information System (INIS)

    This paper conveys a philosophy for developing automated large-scale control systems that behave in an integrated, intelligent, flexible manner. Methods for operating large-scale systems under varying degrees of equipment degradation are discussed, and a design approach that separates the effort into phases is suggested. 5 refs., 1 fig

  5. Large Scale Computations in Air Pollution Modelling

    DEFF Research Database (Denmark)

    Zlatev, Z.; Brandt, J.; Builtjes, P. J. H.;

    Proceedings of the NATO Advanced Research Workshop on Large Scale Computations in Air Pollution Modelling, Sofia, Bulgaria, 6-10 July 1998......Proceedings of the NATO Advanced Research Workshop on Large Scale Computations in Air Pollution Modelling, Sofia, Bulgaria, 6-10 July 1998...

  6. The algebras of large N matrix mechanics

    International Nuclear Information System (INIS)

    Extending early work, we formulate the large N matrix mechanics of general bosonic, fermionic and supersymmetric matrix models, including Matrix theory: The Hamiltonian framework of large N matrix mechanics provides a natural setting in which to study the algebras of the large N limit, including (reduced) Lie algebras, (reduced) supersymmetry algebras and free algebras. We find in particular a broad array of new free algebras which we call symmetric Cuntz algebras, interacting symmetric Cuntz algebras, symmetric Bose/Fermi/Cuntz algebras and symmetric Cuntz superalgebras, and we discuss the role of these algebras in solving the large N theory. Most important, the interacting Cuntz algebras are associated to a set of new (hidden) local quantities which are generically conserved only at large N. A number of other new large N phenomena are also observed, including the intrinsic nonlocality of the (reduced) trace class operators of the theory and a closely related large N field identification phenomenon which is associated to another set (this time nonlocal) of new conserved quantities at large N

  7. Particle creation and Dirac's large numbers hypothesis

    International Nuclear Information System (INIS)

    Reference is made to cosmologies based on Dirac's large numbers hypothesis (Nature 139:323 (1937) and Proc. Roy. Soc. A333:403 (1973)). Dirac suggested that continuous creation of matter is required. Two modes of particle creation have been proposed and cosmological models corresponding to each mode have been studied. It is here shown that, within the context of the large numbers hypothesis, the number of particles in the Universe varies as expected (N proportional to t2) so that particle creation is unnecessary. Some undesirable features of cosmologies based on the large numbers hypothesis are also discussed. In order to appreciate fully the results presented for cosmologies based on the large numbers hypothesis a review is made of the corresponding relationship in conventional cosmologies in which the gravitational constant G does not vary with time. It is found, amongst other things that there is no nucleosynthesis in cosmologies based on the large numbers hypothesis, making the large and uniform abundance of He inexplicable. Another undesirable finding with the large numbers hypothesis is the extremely steep decline in the number of particles in the Universe with increasing temperature. Yet another undesirable finding concerns the scattering of photons by electrons in the early Universe; there is no way to establish thermodynamic equilibrium between the photons and electrons, and the black body spectrum of the background radiation is without explanation. (U.K.)

  8. A large electrically excited synchronous generator

    DEFF Research Database (Denmark)

    2014-01-01

    This invention relates to a large electrically excited synchronous generator (100), comprising a stator (101), and a rotor or rotor coreback (102) comprising an excitation coil (103) generating a magnetic field during use, wherein the rotor or rotor coreback (102) further comprises a plurality of...... adjacent neighbouring poles. In this way, a large electrically excited synchronous generator (EESG) is provided that readily enables a relatively large number of poles, compared to a traditional EESG, since the excitation coil in this design provides MMF for all the poles, whereas in a traditional EESG...

  9. Network robustness under large-scale attacks

    CERN Document Server

    Zhou, Qing; Liu, Ruifang

    2012-01-01

    Network Robustness under Large-Scale Attacks provides the analysis of network robustness under attacks, with a focus on large-scale correlated physical attacks. The book begins with a thorough overview of the latest research and techniques to analyze the network responses to different types of attacks over various network topologies and connection models. It then introduces a new large-scale physical attack model coined as area attack, under which a new network robustness measure is introduced and applied to study the network responses. With this book, readers will learn the necessary tools to

  10. Virion Proteomics of Large DNA Viruses

    Institute of Scientific and Technical Information of China (English)

    Ran-ran WANG; Zhi-hong HU; Hua-lin WANG; Fei DENG

    2009-01-01

    Large DNA viruses normally have complex structures with many of protein components derived from both viral and host origins. The development in proteomics, especially mass spectrometry identification techniques provide powerful tools for analyzing large viruses. In this review, we have summarized the recent achievements on proteomic studies of large DNA viruses, such as herpesvirus, poxvirus, nimavirus and baculoviruse. The proteomics of baculovirus occlusion-derived virions (ODV) were emphasized. Different mass spectrometry techniques used on ,carious baculoviruses were introduced, and the identified structurally associated proteins of baculoviruses are summarized.

  11. Has Job Security Vanished in Large Corporations?

    OpenAIRE

    Steven G. Allen; Clark, Robert L.; Sylvester J. Schieber

    1999-01-01

    The prevailing wisdom in media accounts is that job stability has vanished, especially for those in large corporations. Academic studies of job stability have found little difference between the 1990s and earlier decades, but these studies have not been able to focus on large firms. This paper provides the first detailed analysis of job stability in large corporations in the 1990s using a sample of 51 firms that are clients of Watson Wyatt Worldwide. We find that mean tenure and the percentag...

  12. Very Large System Dynamics Models - Lessons Learned

    Energy Technology Data Exchange (ETDEWEB)

    Jacob J. Jacobson; Leonard Malczynski

    2008-10-01

    This paper provides lessons learned from developing several large system dynamics (SD) models. System dynamics modeling practice emphasize the need to keep models small so that they are manageable and understandable. This practice is generally reasonable and prudent; however, there are times that large SD models are necessary. This paper outlines two large SD projects that were done at two Department of Energy National Laboratories, the Idaho National Laboratory and Sandia National Laboratories. This paper summarizes the models and then discusses some of the valuable lessons learned during these two modeling efforts.

  13. Synthesis of Small and Large scale Dynamos

    CERN Document Server

    Subramanian, K

    2000-01-01

    Using a closure model for the evolution of magnetic correlations, we uncover an interesting plausible saturated state of the small-scale fluctuation dynamo (SSD) and a novel anology between quantum mechanical tunneling and the generation of large-scale fields. Large scale fields develop via the $\\alpha$-effect, but as magnetic helicity can only change on a resistive timescale, the time it takes to organize the field into large scales increases with magnetic Reynolds number. This is very similar to the results which obtain from simulations using full MHD.

  14. 1919 + 742 - A large double radio source

    Science.gov (United States)

    Strom, R. G.; Eckart, A.; Biermann, P.

    1985-10-01

    A 49-cm map of the source 1919 + 742 (previously catalogued as 4C74.24 and NB74.26) shows it to be a large double. Although the optical identification is unclear, there are several candidate objects near the source centroid which appear to be members of a small group of galaxies. The absence of bright identification candidates argues for a moderately distant, and hence intrinsically large (750 kpc overall size for z = 0.1) object. The spectrum between 80 and 600 MHz is determined, some intrinsic properties are derived, and these are briefly discussed in the context of other large sources.

  15. Large scale network-centric distributed systems

    CERN Document Server

    Sarbazi-Azad, Hamid

    2014-01-01

    A highly accessible reference offering a broad range of topics and insights on large scale network-centric distributed systems Evolving from the fields of high-performance computing and networking, large scale network-centric distributed systems continues to grow as one of the most important topics in computing and communication and many interdisciplinary areas. Dealing with both wired and wireless networks, this book focuses on the design and performance issues of such systems. Large Scale Network-Centric Distributed Systems provides in-depth coverage ranging from ground-level hardware issu

  16. Interference Mitigation in Large Random Wireless Networks

    CERN Document Server

    Aldridge, Matthew

    2011-01-01

    A central problem in the operation of large wireless networks is how to deal with interference -- the unwanted signals being sent by transmitters that a receiver is not interested in. This thesis looks at ways of combating such interference. In Chapters 1 and 2, we outline the necessary information and communication theory background, including the concept of capacity. We also include an overview of a new set of schemes for dealing with interference known as interference alignment, paying special attention to a channel-state-based strategy called ergodic interference alignment. In Chapter 3, we consider the operation of large regular and random networks by treating interference as background noise. We consider the local performance of a single node, and the global performance of a very large network. In Chapter 4, we use ergodic interference alignment to derive the asymptotic sum-capacity of large random dense networks. These networks are derived from a physical model of node placement where signal strength d...

  17. Bipartite Graphs of Large Clique-Width

    Science.gov (United States)

    Korpelainen, Nicholas; Lozin, Vadim V.

    Recently, several constructions of bipartite graphs of large clique-width have been discovered in the literature. In the present paper, we propose a general framework for developing such constructions and use it to obtain new results on this topic.

  18. Cyclotomy and permutation polynomials of large indices

    OpenAIRE

    WANG Qiang

    2012-01-01

    We use cyclotomy to design new classes of permutation polynomials over finite fields. This allows us to generate many classes of permutation polynomials in an algorithmic way. Many of them are permutation polynomials of large indices.

  19. Generalized parton distributions at large momentum transfer

    OpenAIRE

    Kroll, P.

    2001-01-01

    The role of generalized parton distributions in wide-angle exclusive reactions will be discussed. In contrast to deep virtual exclusive reactions the wide angle processes offer the possibility of investigating the generalized parton distributions at large momentum transfer.

  20. Growth Limits in Large Scale Networks

    DEFF Research Database (Denmark)

    Knudsen, Thomas Phillip

    main focus. Here the general perception of the nature and role in society of large scale networks as a fundamental infrastructure is analysed. This analysis focuses on the effects of the technical DDN projects and on the perception of network infrastructure as expressed by key decision makers. A......The Subject of large scale networks is approached from the perspective of the network planner. An analysis of the long term planning problems is presented with the main focus on the changing requirements for large scale networks and the potential problems in meeting these requirements. The problems...... fundamental technological resources in network technologies are analysed for scalability. Here several technological limits to continued growth are presented. The third step involves a survey of major problems in managing large scale networks given the growth of user requirements and the technological...

  1. Large-bandwidth planar photonic crystal waveguides

    DEFF Research Database (Denmark)

    Søndergaard, Thomas; Lavrinenko, Andrei

    defect has appropriate dispersion properties relative to the photonic crystal slab material surrounding the line defect. A three-dimensional theoretical analysis is given for large-bandwidth waveguide designs based on a silicon-air photonic crystal slab suspended in air. In one example, the leakage......A general design principle is presented for making finite-height photonic crystal waveguides that support leakage-free guidance of light over large frequency intervals. The large bandwidth waveguides are designed by introducing line defects in photonic crystal slabs, where the material in the line......-free single-mode guidance is found for a large frequency interval covering 60% of the photonic band-gap....

  2. Preparing for the Large Hadron Collider

    CERN Document Server

    Appleton, Owen

    2007-01-01

    "Processing data for the Large Hadron Collider, the next-generation particle accelerator under construction at CERN, Switzerland, is one of the driving forces for development of Grid technology." (1 page)

  3. Large Area Sputter Coating on Glass

    Science.gov (United States)

    Katayama, Yoshihito

    Large glass has been used for commercial buildings, housings and vehicles for many years. Glass size for flat displays is getting larger and larger. The glass for the 8th generation is more than 5 m2 in area. Demand of the large glass is increasing not only in these markets but also in a solar cell market growing drastically. Therefore, large area coating is demanded to plus something else on glass more than ever. Sputtering and pyrolysis are the major coating methods on large glass today. Sputtering process is particularly popular because it can deposit a wide variety of materials in good coating uniformity on the glass. This paper describes typical industrial sputtering system and recent progress in sputtering technology. It also shows typical coated glass products in architectural, automotive and display fields and comments on their functions, film stacks and so on.

  4. Laparoscopic transperitoneal ureterolithotomy for large ureteric stones

    Directory of Open Access Journals (Sweden)

    Ahmed Al-Sayyad

    2012-01-01

    Conclusion: Laparoscopic transperitoneal ureterolithotomy is a safe and effective approach for selected patients with large proximal ureteric stones with reduced postoperative pain and short hospital stay, and should be considered as a treatment option for such stones.

  5. Data Mining And Visualization of Large Databases

    Directory of Open Access Journals (Sweden)

    AbdulRahman R. Alazmi

    2012-10-01

    Full Text Available Data Mining and Visualization are tools that are used in databases to further analyse and understand the stored data. Data mining and visualization are knowledge discovery tools used to find hidden patterns and to visualize the data distribution. In the paper, we shall illustrate how data mining and visualization are used in large databases to find patterns and traits hidden within. In large databases where data is both large and seemingly random, mining and visualization help to find the trends found in such large sets. We shall look at the developments of data mining and visualization and what kind of application fields usage of such tools. Finally, we shall touch upon the future developments and newer trends in data mining and visualization being experimented for future use.

  6. Large eddy simulation of turbulent swirling jets

    OpenAIRE

    García-Villalba Navaridas, Manual

    2006-01-01

    Annulare und co-annulare Drallstrahlen werden oft bei Verbrennungsmaschinen wie z.B. von Gasturbinen eingesetzt. In der vorliegenden Arbeit wurden annulare und co-annulare Drallstrahlen mit Hilfe der Large-Eddy Simulation untersucht.

  7. HI Imaging of the Large Magellanic Cloud

    OpenAIRE

    Kim, S.; Staveley-Smith, L; Sault, R. J.

    2000-01-01

    We present results from the combined Australia Telescope Compact Array (ATCA) aperture synthesis mosaic survey of HI emission in the Large Magellanic Cloud with 64m Parkes single dish telescope observations.

  8. Interacting on and around Large Displays

    DEFF Research Database (Denmark)

    Markussen, Anders

    version of the keyboard even showed text entry rates of 28.1 WPM on the first session of an accelerated learning study where a limited set of phrases were repeatedly transcribed. Paper 3 build on the result from Paper 1 and Paper 2, and propose new directions for text entry research for large displays. To...... explore the potential interaction techniques supported by this novel tracking solution, and assess its potential to work as a new input modality for large displays. Finally, Paper 5 presents Off-Limits, a novel interaction concept for large displays that uses off-screen pointing to allow direct reach of...... focus of this thesis is on three aspects of large display interactions: (1) Improved Mid-Air Text Entry; (2) Improved Understanding of Input Modalities; and (3) Extended Boundaries of Interaction. To improve support for mid-air text entry, Paper 1 conducted a design space analysis, and three mid...

  9. Logarithmic potential theory and large deviation

    OpenAIRE

    Bloom, T.; Levenberg, N.; Wielonsky, F.

    2014-01-01

    We derive a general large deviation principle for a canonical sequence of probability measures, having its origins in random matrix theory, on unbounded sets $K$ of ${\\bf C}$ with weakly admissible external fields $Q$ and very general measures $\

  10. Roentgenoanatomy and physiology of large intestine

    International Nuclear Information System (INIS)

    Characteristics of sections of the colon and rectum is given. Alongside with roentgenoanatomic description of sections of the large intestine, biological functions and roentgenological indications for pathological changes, are presented

  11. Cosmogenic Nuclides Study of Large Iron Meteorites

    Science.gov (United States)

    Hutzler, A.; Smith, T.; Rochette, P.; Bourles, D. L.; Leya, I.; Gattacceca, J.

    2014-09-01

    Six large iron meteorites were selected (Saint-Aubin, Mont-Dieu, Caille, Morasko, Agoudal, and Gebel Kamil). We measured stable and radiogenic cosmogenic nuclides, to study pre-atmospheric size, cosmic-ray exposure ages and terrestrial ages.

  12. Large & Small: Exploring the Laws of Nature

    Science.gov (United States)

    Creutz, E.

    1976-01-01

    Illustrates how both large entities (such as stars and galaxies) and small entities (such as fundamental particles) obey the same physical laws. Discusses quantum mechanics, Newton's laws, and general relativity. (MLH)

  13. On Carleman estimates with two large parameters

    International Nuclear Information System (INIS)

    We provide a general framework for the analysis and the derivation of Carleman estimates with two large parameters. For an appropriate form of weight functions strong pseudo-convexity conditions are shown to be necessary and sufficient.

  14. Enhanced performance large volume dissolution-DNP

    DEFF Research Database (Denmark)

    Bowen, Sean; Ardenkjær-Larsen, Jan Henrik

    2014-01-01

    A systematic study of the performance of the dissolution process in dissolution-DNP is presented. A relatively simple set of modifications is made to the standard Hypersense dissolution system to enable polarization of large volume samples. These consist of a large volume sample cup along with...... supporting modifications to the dissolution head and related components. Additional modifications were made to support the mapping of the temperature/pressure space of the dissolution process as well as enabling the use of large volumes of solvent and improving the robustness of the system. No loss of...... polarization was observed as sample size was increased to the 1g capacity of the large volume cup and for a dilution factor as low as 1:10....

  15. Gravitational Wilson Loop and Large Scale Curvature

    OpenAIRE

    Hamber, H.; Williams, R.

    2007-01-01

    In a quantum theory of gravity the gravitational Wilson loop, defined as a suitable quantum average of a parallel transport operator around a large near-planar loop, provides important information about the large-scale curvature properties of the geometry. Here we shows that such properties can be systematically computed in the strong coupling limit of lattice regularized quantum gravity, by performing local averages over loop bivectors, and over lattice rotations, using an assumed near-unifo...

  16. Large generalized books are p-good

    OpenAIRE

    Nikiforov, Vladimir; Rousseau, Cecil

    2004-01-01

    An r-book of size q is a union of q (r+1)-cliques sharing a common r-clique. We find exactly the Ramsey number of a p-clique versus r-books of sufficiently large size. Furthermore, we find asymptotically the Ramsey number of any fixed p-chromatic graph versus r-books of sufficiently large size. The key element in our proofs is Szemeredi's Regularity Lemma.

  17. Large Format Detector Arrays for Astrophysics

    Science.gov (United States)

    Moseley, Harvey

    2006-01-01

    Improvements in detector design and advances in fabrication techniques has resulted in devices which can reach fundamental sensitivity limits in many cases. Many pressing astrophysical questions require large arrays of such sensitive detectors. I will describe the state of far infrared through millimeter detector development at NASA/GSFC, the design and production of large format arrays, and the initial deployment of these powerful new tools.

  18. Charged rotating black holes at large D

    OpenAIRE

    Tanabe, Kentaro

    2016-01-01

    We study odd dimensional charged equally rotating black holes in the Einstein-Maxwell theory with/without a cosmological constant by using the large D expansion method, where D is a spacetime dimension. Solving the Einstein-Maxwell equations in the 1/D expansion we obtain the large D effective equations for charged equally rotating black holes. The effective equations describe the nonlinear dynamics of charged equally rotating black holes. Especially the perturbation analysis of the effective...

  19. Small Price Responses to Large Demand Shocks

    OpenAIRE

    Gagnon, Etienne; López-Salido, J David

    2015-01-01

    We study the pricing response of U.S. supermarkets to large demand shocks triggered by labor conflicts, mass population relocation, and shopping sprees around major snowstorms and hurricanes. We find that these large swings in demand have, at best, modest effects on the level of retail prices, consistent with flat short- to medium-term supply curves. This finding holds even when shocks are highly persistent and even though stores adjust prices frequently. We also uncover evidence that retaile...

  20. ALMA (Atacama Large Millimetre/ Submillimetre Array)

    OpenAIRE

    Barcons, Xavier

    2010-01-01

    ALMA is a large sub/millimetre observatory in construction phase (Atacama desert, Chile). When finished it will be the world’s largest interferometer for millimetre and submillimetre wavelengths. Three sites: 1)Array Operations Site (AOS), llano de Chajnantor (5100 m). 2)Operations Support Facility (OSF), near San Pedro de Atacama (2900m). 3)Santiago Central Office (SCO). First large ground-based “global” scientific infrastructure.

  1. Large granular lymphocytosis associated with rheumatoid arthritis.

    OpenAIRE

    Samanta, A; GRANT, I.; Nichol, F E; Pringle, J H; Wood, J. K.; Campbell, A. C.

    1988-01-01

    A 74 year old woman with rheumatoid arthritis, hepatosplenomegaly, neutropenia, and peripheral blood lymphocytosis is described. The lymphocytes had a large granular morphology and expressed a CD3+ CD8+ Leu7+ surface antigen phenotype. They did not have natural killer cell function. Southern analysis of the lymphocyte DNA using two restriction enzymes showed a rearranged pattern for the T cell receptor beta chain gene, indicating a monoclonal lymphoproliferation. Large granular lymphocytosis ...

  2. Comments on Large N Matrix Model

    CERN Document Server

    Kajiura, H; Ogushi, S; Kajiura, Hiroshige; Kato, Akishi; Ogushi, Sachiko

    2000-01-01

    The large N Matrix model is studied with attention to the quantum fluctuations around a given diagonal background. Feynman rules are explicitly derived and their relation to those in usual Yang-Mills theory is discussed. Background D-instanton configuration is naturally identified as a discretization of momentum space of a corresponding QFT. The structure of large N divergence is also studied on the analogy of UV divergences in QFT.

  3. Achieving business model innovation in large corporations

    OpenAIRE

    Winterhalter, Stephan; Weiblen, Tobias; Wecht, Christoph; Gassmann, Oliver

    2014-01-01

    Despite the fact that business model innovation (BMI) has attracted intense scholarly attention, there is a paucity of insights concerning the organizational implementation of BMI efforts in large corporations. This paper investigates how business model innovation is managed in the complex environment of the chemical industry and derives consequences for the establishment of a systematic BMI process in large corporations. Based on a multiple case study design, we identify three different type...

  4. Vanishing large ovarian cyst with thyroxine therapy

    OpenAIRE

    Dharmshaktu, Pramila; Kutiyal, Aditya; Dhanwal, Dinesh

    2013-01-01

    Summary A 21-year-old female patient recently diagnosed with severe hypothyroidism was found to have a large ovarian cyst. In view of the large ovarian cyst, she was advised to undergo elective laparotomy in the gynaecology department. She was further evaluated in our medical out-patient department (OPD), and elective surgery was withheld. She was started on thyroxine replacement therapy, and within a period of 4 months, the size of the cyst regressed significantly, thereby improving the cond...

  5. On asymmetric collisions with large disruption parameters

    International Nuclear Information System (INIS)

    Collisions between a weak electron bunch and a strong positron bunch are studied within a flat model. Electrons are tracked through the transverse space charge field of the positron bunch, and it is shown that positrons in a storage ring may remain stable after asymmetric collisions with a weak electron bunch in spite of large values of the electron disruption parameter. The plasma oscillations that affect collisions with large disruption parameters may be suppressed by properly matching the electrons. 8 refs., 5 figs

  6. Model for gravity at large distances

    OpenAIRE

    Grumiller, Daniel(Institute for Theoretical Physics, Vienna University of Technology, Wiedner Hauptstrasse 8-10/136, A-1040, Vienna, Austria)

    2010-01-01

    We construct an effective model for gravity of a central object at large scales. To leading order in the large radius expansion we find a cosmological constant, a Rindler acceleration, a term that sets the physical scales and subleading terms. All these terms are expected from general relativity, except for the Rindler term. The latter leads to an anomalous acceleration in geodesics of test-particles.

  7. Chemical Vapour Deposition of Large Area Graphene

    OpenAIRE

    Larsen, Martin Benjamin Barbour Spanget; Bøggild, Peter; Booth, Tim; Jørgensen, Anders Michael

    2015-01-01

    Chemical Vapor Deposition (CVD) is a viable technique for fabrication of large areas of graphene. CVD fabrication is the most prominent and common way of fabricating graphene in industry. In this thesis I have attempted to optimize a growth recipe and catalyst layer for CVD fabrication of uniform, single layer, and high carrier mobility large area graphene. The main goals of this work are; (1) explore the graphene growth mechanics in a low pressure cold-wall CVD system on a copper substrate, ...

  8. Reliable control of large scale flexible structures

    Czech Academy of Sciences Publication Activity Database

    Bakule, Lubomír

    Gdansk : IFAC - GUT, 2007, s. 1-6. ISSN 1367-5788. [IFAC/IFORS/IMACS/IFIP Symposium on Large Scale Complex Systems: Theory and Applications /11./. Gdansk (PL), 23.07.2007-25.07.2007] R&D Projects: GA AV ČR IAA2075304; GA MŠk(CZ) LA 282 Institutional research plan: CEZ:AV0Z10750506 Keywords : decentralized control * large scale systems * decomposition * reliability * flexible structures * redundancy Subject RIV: BC - Control Systems Theory

  9. Spectral comparison of large urban graphs

    OpenAIRE

    Hanna, S

    2009-01-01

    The spectrum of an axial graph is proposed as a means for comparison between spaces, particularly for measuring between very large and complex graphs. A number of methods have been used in recent years for comparative analysis within large sets of urban areas, both to investigate properties of specific known types of street network or to propose a taxonomy of urban morphology based on an analytical technique. In many cases, a single or small range of predefined, scalar measures...

  10. Eliciting Information from a Large Population

    OpenAIRE

    Kawamura, Kohei

    2013-01-01

    This paper studies information transmission in social surveys where a welfare maximizing decision maker communicates with a random sample of individuals from a large population who have heterogeneous preferences. The population distribution of preferences is unknown and has to be estimated, based on answers from the respondents. The decision maker cannot identify the true distribution of preferences even if the sample size becomes arbitrarily large, since the respondents have incentive to “ex...

  11. Irradiation injuries of the large intestine

    International Nuclear Information System (INIS)

    A series of 15 patients suffering from irradiation injuries to the large bowel is reviewed. Ten patients required surgical intervention; intestinal continuity was re-established in three patients. As only three of the patients developed recurrent carcinoma, the initial operation for irradiation injury to the large bowel should be carefully planned so that the patient is not ultimately cured of carcinoma but left with a permanent stoma

  12. Big Science and the Large Hadron Collider

    OpenAIRE

    Giudice, Gian Francesco

    2011-01-01

    The Large Hadron Collider (LHC), the particle accelerator operating at CERN, is probably the most complex and ambitious scientific project ever accomplished by humanity. The sheer size of the enterprise, in terms of financial and human resources, naturally raises the question whether society should support such costly basic-research programs. I address this question here by first reviewing the process that led to the emergence of Big Science and the role of large projects in the development o...

  13. Large Eddy Simulation in internal combustion Engine

    OpenAIRE

    Ghelfi, Matteo

    2013-01-01

    Abstract Large Eddy Simulation in internal combustion Engine Dipl.-Ing Matteo Ghel� The internal combustion (IC) engine simulation is nowadays one of the most difficult proceeding during engine development. Simultaneously this is one of the most important phase because it leads to better acknowledgment of in-cylinder phenomena and suggests new method of emission reduction and control.\\\\ Large Eddy Simulation (LES) can help this process because of its instationary nature, in perfec...

  14. Spatial Indexing of Large Multidimensional Databases

    OpenAIRE

    Csabai, István; Trencséni, Márton; Herczegh, Géza; Dobos, László; Józsa, Péter; Purger, Norbert; Budavári, Tamás; Szalay, Alexander

    2012-01-01

    Scientific endeavors such as large astronomical surveys generate databases on the terabyte scale. These, usually multidimensional databases must be visualized and mined in order to find interesting objects or to extract meaningful and qualitatively new relationships. Many statistical algorithms required for these tasks run reasonably fast when operating on small sets of in-memory data, but take noticeable performance hits when operating on large databases that do not fit into memory. We utili...

  15. A very large multigap resistive plate chamber

    CERN Document Server

    Cerron-Zeballos, E; Hatzifotiadou, D; Kim, D W; Lamas-Valverde, J; Lee, S C; Platner, E D; Roberts, J; Williams, M C S; Zichichi, A

    1999-01-01

    We have built and tested a very large multigap resistive plate chamber (MRPC). We discuss the suitability of the multigap RPC for the construction of large area modules. We give details of the construction technique and results from a scan across the surface of the chamber. We also report on the implementation of `half-strip resolution', where we improve the spatial resolution by a factor 2 without increasing the number of read-out channels. (9 refs).

  16. Zone generator for Large Space Telescope technology

    Science.gov (United States)

    Erickson, K. E.

    1974-01-01

    A concept is presented for monitoring the optical adjustment and performance of a Large Space Telescope which consists of a 1.2m diameter turntable with a laser stylus to operate at speeds up to 30 rpm. The focus of the laser stylus is under closed loop control. A technique for scribing zones of suitable depth, width, and uniformity applicable to large telescope mirrors is also reported.

  17. Andlantis: Large-scale Android Dynamic Analysis

    OpenAIRE

    Bierma, Michael; Gustafson, Eric; Erickson, Jeremy; Fritz, David; Choe, Yung Ryn

    2014-01-01

    Analyzing Android applications for malicious behavior is an important area of research, and is made difficult, in part, by the increasingly large number of applications available for the platform. While techniques exist to perform static analysis on a large number of applications, dynamic analysis techniques are relatively limited in scale due to the computational resources required to emulate the full Android system to achieve accurate execution. We present Andlantis, a scalable dynamic anal...

  18. Probability estimation and compression involving large alphabets

    OpenAIRE

    Santhanam, Narayana

    2006-01-01

    Many results in statistics and information theory are asymptotic in nature, with the implicit assumption that we operate in a regime where the data size is much larger than the alphabet size. In this dissertation, we will be concerned with large alphabets, namely alphabets for which the above assumption does not hold. We consider universal compression, i.e., compression when data statistics are unknown, and probability estimation involving data drawn from large alphabets. Both these problems ...

  19. Effective Language Teaching in Large Classes

    Institute of Scientific and Technical Information of China (English)

    张丽丽

    2010-01-01

    <正>With more and more people who are jumping into the line of learning the second language (especially English),and also due to the limited resources in language teaching,many foreign language teachers are nowadays confronting the large classes when teaching.So how to teach foreign language effectively in large classes has become an issue as well as a special field to make researches in.

  20. Financing Large-scale EU Infrastructure Projects

    OpenAIRE

    Latreille, Thierry; Sterdyniak, Henri; Veroni, Paola

    2000-01-01

    This study discusses the proposal which consists of financing large-scale infrastructure investments by issuing EU bonds, first introduced by President Delors in his White Paper on “Growth, Competitiveness and Employment” in 1993. This proposal has been partly implemented insofar as the European Commission and the EIB have financed a number of large projects. But it is not considered as a major tool of European economic policy. Monetary policy is the major instrument of short a...