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Sample records for anaplastic large cell

  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

    Institute of Scientific and Technical Information of China (English)

    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

    DEFF Research Database (Denmark)

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

    OpenAIRE

    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...

  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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    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

  10. 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.

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

    OpenAIRE

    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...

  13. 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.

  14. 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.

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

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    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...

  17. 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

  18. 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.

  19. 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.

  20. 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.)

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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.

  7. 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.

  8. 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

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

    Institute of Scientific and Technical Information of China (English)

    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.

  10. 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

  11. 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.

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

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    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

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

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    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

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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

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

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

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    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.

  2. 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...

  3. {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.

  4. 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

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

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    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.

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

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    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.

  7. 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

  8. 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

  9. 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

  10. 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...

  11. 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...

  12. 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

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

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    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.

  14. 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...

  15. 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

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. 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

  1. 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...

  2. [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

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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)

  8. 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.)

  9. 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

  10. 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

  11. 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...

  12. 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

  13. 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

  14. 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.

  15. 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...

  16. 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.

  17. 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

  18. 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

  19. 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

  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. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  3. 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

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

    Directory of Open Access Journals (Sweden)

    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 

  5. 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...

  6. Effects of BP-14, a novel cyclin-dependent kinase inhibitor, on anaplastic thyroid cancer cells

    Czech Academy of Sciences Publication Activity Database

    Allegri, L.; Baldan, F.; Mio, F.; Puppin, C.; Russo, D.; Kryštof, Vladimír; Damante, G.

    2016-01-01

    Roč. 35, č. 4 (2016), s. 2413-2418. ISSN 1021-335X R&D Projects: GA ČR(CZ) GA15-15264S Institutional support: RVO:61389030 Keywords : mTOR * thyroid cancer * cell proliferation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.301, year: 2014

  7. 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

  8. 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.

  9. 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.)

  10. 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

  11. 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

  12. 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.

  13. 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...

  14. 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...

  15. 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.

  16. 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

  17. 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.

  18. 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

  19. 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

  20. Combination Chemotherapy and Lenalidomide in Treating Patients With Newly Diagnosed Stage II-IV Peripheral T-cell Non-Hodgkin's Lymphoma

    Science.gov (United States)

    2015-10-02

    Anaplastic Large Cell Lymphoma, ALK-Negative; Anaplastic Large Cell Lymphoma, ALK-Positive; Hepatosplenic T-Cell Lymphoma; Peripheral T-Cell Lymphoma, Not Otherwise Specified; Stage II Angioimmunoblastic T-cell Lymphoma; Stage II Enteropathy-Associated T-Cell Lymphoma; Stage III Angioimmunoblastic T-cell Lymphoma; Stage III Enteropathy-Associated T-Cell Lymphoma; Stage IV Angioimmunoblastic T-cell Lymphoma; Stage IV Enteropathy-Associated T-Cell Lymphoma

  1. The tyrosine phosphatase Shp2 interacts with NPM-ALK and regulates anaplastic lymphoma cell growth and migration

    DEFF Research Database (Denmark)

    Voena, Claudia; Conte, Chiara; Ambrogio, Chiara; Boeri Erba, Elisabetta; Boccalatte, Francesco; Mohammed, Shabaz; Jensen, Ole N; Palestro, Giorgio; Inghirami, Giorgio; Chiarle, Roberto

    2007-01-01

    , leading to increased cell growth, resistance to apoptosis, and changes in morphology and migration of transformed cells. To search for new NPM-ALK interacting molecules, we developed a mass spectrometry-based proteomic approach in HEK293 cells expressing an inducible NPM-ALK and identified the tyrosine...

  2. 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

  3. 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.

  4. 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

  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. 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...

  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. 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

  9. 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

  10. 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.

  11. 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

  12. 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

  13. Primary nodal peripheral T-cell lymphomas: diagnosis and therapeutic considerations

    Directory of Open Access Journals (Sweden)

    Luis Alberto de Pádua Covas Lage

    2015-08-01

    Full Text Available Nodal peripheral T-cell lymphomas are a rare group of neoplasms derived from post-thymic and activated T lymphocytes. A review of scientific articles listed in PubMed, Lilacs, and the Cochrane Library databases was performed using the term "peripheral T-cell lymphomas". According to the World Health Organization classification of hematopoietic tissue tumors, this group of neoplasms consists of peripheral T-cell lymphoma not otherwise specified (PTCL-NOS, angioimmunoblastic T-cell lymphoma (AITL, anaplastic large cell lymphoma-anaplastic lymphoma kinase positive (ALCL-ALK+, and a provisional entity called anaplastic large cell lymphoma-anaplastic lymphoma kinase negative (ALCL-ALK-. Because the treatment and prognoses of these neoplasms involve different principles, it is essential to distinguish each one by its clinical, immunophenotypic, genetic, and molecular features. Except for anaplastic large cell lymphoma-anaplastic lymphoma kinase positive, which has no adverse international prognostic index, the prognosis of nodal peripheral T-cell lymphomas is worse than that of aggressive B-cell lymphomas. Chemotherapy based on anthracyclines provides poor outcomes because these neoplasms frequently have multidrug-resistant phenotypes. Based on this, the current tendency is to use intensified cyclophosphamide, doxorubicin, vincristine, prednisolone (CHOP regimens with the addition of new drugs, and autologous hematopoietic stem cell transplantation. This paper describes the clinical features and diagnostic methods, and proposes a therapeutic algorithm for nodal peripheral T-cell lymphoma patients.

  14. 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.

  15. A Pilot Feasibility Study of Oral 5-Fluorocytosine and Genetically-Modified Neural Stem Cells Expressing E.Coli Cytosine Deaminase for Treatment of Recurrent High Grade Gliomas

    Science.gov (United States)

    2015-03-02

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

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

    Science.gov (United States)

    2013-01-15

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

  17. 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

  18. 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

  19. 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...

  20. 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.

  1. 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

  2. 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

  3. 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

  4. 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.

  5. 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.

  6. Detecting cell assemblies in large neuronal populations.

    Science.gov (United States)

    Lopes-dos-Santos, Vítor; Ribeiro, Sidarta; Tort, Adriano B L

    2013-11-15

    Recent progress in the technology for single unit recordings has given the neuroscientific community the opportunity to record the spiking activity of large neuronal populations. At the same pace, statistical and mathematical tools were developed to deal with high-dimensional datasets typical of such recordings. A major line of research investigates the functional role of subsets of neurons with significant co-firing behavior: the Hebbian cell assemblies. Here we review three linear methods for the detection of cell assemblies in large neuronal populations that rely on principal and independent component analysis. Based on their performance in spike train simulations, we propose a modified framework that incorporates multiple features of these previous methods. We apply the new framework to actual single unit recordings and show the existence of cell assemblies in the rat hippocampus, which typically oscillate at theta frequencies and couple to different phases of the underlying field rhythm. PMID:23639919

  7. Primary Hepatosplenic Large B-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    M.R. Morales-Polanco

    2008-03-01

    Full Text Available Diffuse large B-cell lymphoma is the most common form of lymphoma. It usually begins in the lymph nodes; up to 40% may have an extranodal presentation. According to a definition of primary extranodal lymphoma with presentation only in extranodal sites, there are reports of large B-cell lymphomas limited to liver or spleen as separate entities, and to date there have been only three documented cases of primary hepatosplenic presentation. This paper reports a fourth case. Due to a review of the literature and the clinical course of the case reported, we conclude that primary hepatosplenic large B-cell lymphoma has been found predominantly in females older than 60 years. The patients reported had <2 months of evolution prior to diagnosis, prominent B symptoms, splenomegaly in three and hepatomegaly in two, none with lymph node involvement. All had thrombocytopenia and abnormal liver function tests; three had anemia and elevated serum lactic dehydrogenase levels, two with hemophagocytosis in bone marrow. Because of the previously mentioned data, it can be stated that primary hepatosplenic lymphoma is an uncommon and aggressive form of disease that requires immediate recognition and treatment.

  8. 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

  9. Mediastinal large cell lymphoma with sclerosis

    International Nuclear Information System (INIS)

    Five cases of primary mediastinal large-cell lymphoma with sclerosis diagnosed at the University Hospital Clementino Fraga Filho (Federal University of Rio de Janeiro) between 1986 and 1994 were identified. They were studied on clinical, morphological and immuno-histochemical grounds. Clinically, the disease was characterized by the young age of the patients, mediastinal involvement by bulky disease and compressive symptoms. None of the patients had evidence of extra-thoracic disease as presentation. On morphological grounds they had evidence of extra-thoracic disease at presentation. On morphological grounds they showed a mixture of immuno blasts and large follicular enter cell with sclerosis. Three of five cases proved to be of B-cell origin. Four of five patients were treated with chemotherapy. Cases 1 and with MACOP-B, and cases 3 and 4 with Pro-MACE-cytaBOM and consolidation radiation therapy. All the patients achieved a complete remission, and are alive, free of disease, with a follow-up of 1 to 8 years. (author). 28 refs., 8 figs., 2 tabs

  10. 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.

  11. 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

  12. Clear cell carcinoma of the lung.

    OpenAIRE

    Edwards, C; Carlile, A

    1985-01-01

    Six tumours of the lung initially classified as clear cell carcinoma, were studied. Examination of further material by light and electron microscopy showed adenocarcinomatous differentiation in three cases and squamous differentiation in two. One case showed the features of a large cell anaplastic carcinoma. The clear appearance of the cytoplasm in paraffin sections was due to accumulations of glycogen that were partially removed during processing. It is concluded that clear cell carcinoma is...

  13. 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.

  14. 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

  15. Sialylation and glycosylation modulate cell adhesion and invasion to extracellular matrix in human malignant lymphoma: Dependency on integrin and the Rho GTPase family

    OpenAIRE

    Suzuki, Osamu; Abe, Masafumi; HASHIMOTO, YUKO

    2015-01-01

    To determine the biological roles of cell surface glycosylation, we modified the surface glycosylation of human malignant lymphoma cell lines using glycosylation inhibitors. The O-glycosylation inhibitor, benzyl-α-GalNAc (BZ) enhanced the fibronectin adhesion of HBL-8 cells, a human Burkitt's lymphoma cell line, and of H-ALCL cells, a human anaplastic large cell lymphoma cell line, both of which were established in our laboratory. The N-glycosylation inhibitor, tunicamycin (TM) inhibited the ...

  16. 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

  17. 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.

  18. Intracranial Orthotopic Allografting of Medulloblastoma Cells in Immunocompromised Mice

    OpenAIRE

    Huang, Xi; Sarangi, Anuraag; Ketova, Tatiana; LItingtung, Ying; Cooper, Michael K.; Chiang, Chin

    2010-01-01

    Medulloblastoma is the most common pediatric tumor of the nervous system. A large body of animal studies has focused on cerebellar granule neuron precursors (CGNPs) as the cell-of-origin for medulloblastoma1-4. However, the diverse clinical presentations of medulloblastoma subtypes in human patients (nodular, desmoplastic, classical and large cell/anaplastic), and the fact that medulloblastoma is found in a subset of human patients with no ectopic expression of CGNP marker5, suggest that the ...

  19. 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.

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

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    Maher Kurdi

    2014-01-01

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

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. 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

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

    Science.gov (United States)

    2016-05-10

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

  9. Large animal models for stem cell therapy

    OpenAIRE

    Harding, John; Roberts, R. Michael; Mirochnitchenko, Oleg

    2013-01-01

    The field of regenerative medicine is approaching translation to clinical practice, and significant safety concerns and knowledge gaps have become clear as clinical practitioners are considering the potential risks and benefits of cell-based therapy. It is necessary to understand the full spectrum of stem cell actions and preclinical evidence for safety and therapeutic efficacy. The role of animal models for gaining this information has increased substantially. There is an urgent need for nov...

  10. Enrichment and Function Research of Large Cell Lung Cancer Stem Cell-like Cells

    OpenAIRE

    Wenke YUE; JIAO, FENG; Liu, Bin; Jiacong YOU; Zhou, Qinghua

    2011-01-01

    Background and objective There are no universal method to recognize and screen for lung cancer stem cell markers and indicators. Commonly used methods are flow Cytometry and learning from other cancer stem cell sorting tags to sort lung cancer stem cells. But this method has low specificity screening, the workload is huge. In this study, Serum-free suspension culture was used to enrich lung cancer stem cells, and explore method for lung cancer stem cell screening. Methods Human large lung can...

  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. Alemtuzumab, Fludarabine Phosphate, and Low-Dose Total Body Irradiation Before Donor Stem Cell Transplantation in Treating Patients With Hematological Malignancies

    Science.gov (United States)

    2016-01-05

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Phase Chronic Myelogenous Leukemia; Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Peripheral T-cell Lymphoma; Previously Treated Myelodysplastic Syndromes; Progressive Hairy Cell Leukemia, Initial Treatment; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Acute

  14. 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.

  15. Large Animal Models of Hematopoietic Stem Cell Gene Therapy

    OpenAIRE

    Trobridge, Grant D.; Kiem, Hans-Peter

    2010-01-01

    Large animal models have been instrumental in advancing hematopoietic stem cell (HSC) gene therapy. Here we review the advantages of large animal models, their contributions to the field of HSC gene therapy, and recent progress in this field. Several properties of human HSCs including their purification, their cell-cycle characteristics, their response to cytokines, and the proliferative demands put on them after transplantation are more similar in large animal models than in mice. Progress i...

  16. 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

  17. 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.

  18. Enrichment and Function Research of Large Cell Lung Cancer Stem Cell-like Cells

    Directory of Open Access Journals (Sweden)

    Wenke YUE

    2011-06-01

    Full Text Available Background and objective There are no universal method to recognize and screen for lung cancer stem cell markers and indicators. Commonly used methods are flow Cytometry and learning from other cancer stem cell sorting tags to sort lung cancer stem cells. But this method has low specificity screening, the workload is huge. In this study, Serum-free suspension culture was used to enrich lung cancer stem cells, and explore method for lung cancer stem cell screening. Methods Human large lung cancer cell line-L9981 was cultured in serum-free and growth factors added medium, and spheres were obtained. Then the morphological differences of sphere cells and adherent L9981 cells cultured in serum-containing mediums are observed. Cell proliferation was analyzed by Vi-cell viability analyzer; invasion ability was tested by transwell assay; and in vivo tumorigenicity of the two groups of cells was studied in nude mouse. Results Compared with adherent L9981 cells cultured in serum-containing mediums, cells cultured in serum-free medium display sphere appearance. Doubling time of adherent cells and sphere cells are (56.05±1.95 h and (33.00±1.44 h respectively; Spheroid cells had higher invasion and tumorigenicity ability, 5 times and 20 times respectively, than adherent cells. Conclusion Suspension cultured L9981 in Serum-free medium could form spheroid populations. Cells in spheres had higher ability of invasion and Tumorigenicity than adherent L9981 cells. These results indicated spheroid L9981 cells contained enriched lung cancer stem cells, and Serum-free suspension culture can be a candidate method for enriching lung cancer stem cell.

  19. 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)

  20. CPI-613 and Bendamustine Hydrochloride in Treating Patients With Relapsed or Refractory T-Cell Non-Hodgkin Lymphoma or Hodgkin Lymphoma

    Science.gov (United States)

    2016-07-26

    Adult Lymphocyte Depletion Hodgkin Lymphoma; Adult Lymphocyte Predominant Hodgkin Lymphoma; Adult Mixed Cellularity Hodgkin Lymphoma; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Adult Nodular Sclerosis Hodgkin Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Hepatosplenic T-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Large Granular Lymphocyte Leukemia

  1. Large cell neuroendocrine carcinoma of the ampulla of Vater.

    LENUS (Irish Health Repository)

    Beggs, Rachel E

    2012-09-01

    Large cell neuroendocrine carcinomas of the ampulla of Vater are rare and confer a very poor prognosis despite aggressive therapy. There are few case reports of large cell neuroendocrine carcinomas of the ampulla of Vater in the literature and to date no studies have been done to establish optimal management. We describe a pooled case series from published reports of neuroendocrine carcinomas of the ampulla of Vater including a case which presented to our institution.

  2. 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

  3. Developmental experiments on large-area silicon solar cells

    Science.gov (United States)

    Silard, Andrei P.; Nani, Gabriel

    1989-05-01

    Practical ways of attenuating the severe limitations imposed by areal inhomogeneities on the performance of large-area solar cells fabricated on both p- and n-silicon wafers are described, and the results of tests are presented. The p(+)-n-n(+) and n(+)-p-p(+) cells were processed as bifacial devices and tested under both frontside and backside AM1 illumination. It is shown that the combination of a simple design and some of the technological approaches evaluated in this study result in low-cost high-efficiency large-area bifacial silicon solar cells that exhibit with good electrooptical performance.

  4. 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).

  5. 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)

  6. 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

  7. Large area high efficiency multicrystalline silicon solar cell

    Science.gov (United States)

    Shirasawa, Katsuhiko; Yamashita, Hironori; Fukui, Kenji; Takayama, Michihiro; Okada, Kenichi

    A high-efficiency, low-cost large-area multicrystalline silicon solar cell having a cell size of 15 cm x 15 cm and a substrate made by the casting method has been developed. The bifacial silicon nitride solar cell (BSNSC) fabrication process was used to construct the cell. By incorporating a new structure at the cell surface, an optimized back-surface field (BSF) process, and an electrode with a ratio of 5.2 percent into the BSNSC fabrication process, a conversion efficiency of 15.1 percent (global, AM1.5, 100 mW/sq cm, 25 C) has been obtained. The uniformity of the electrical performance of the cell has been studied by measuring the distribution of the spectral response at various points on the cell. The results of uniformity testing are presented.

  8. Nuclear localization of Merkel cell polyomavirus large T antigen in Merkel cell carcinoma

    International Nuclear Information System (INIS)

    To clarify whether mutations in the large T gene encoded by Merkel cell polyomavirus affect the expression and function of large T antigen in Merkel cell carcinoma cases, we investigated the expression of large T antigen in vitro and in vivo. Immunohistochemistry using a rabbit polyclonal antibody revealed that large T antigen was expressed in the nuclei of Merkel cell carcinoma cells with Merkel cell polyomavirus infection. Deletion mutant analyses identified an Arg-Lys-Arg-Lys sequence (amino acids 277-280) as a nuclear localization signal in large T antigen. Sequence analyses revealed that there were no mutations in the nuclear localization signal in any of the eleven Merkel cell polyomavirus strains examined. Furthermore, stop codons were not observed in the upstream of the nuclear localization signal in any of the Merkel cell carcinoma cases examined. These data suggest that the nuclear localization signal is highly conserved and functional in Merkel cell carcinoma cases.

  9. 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...

  10. 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...

  11. 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.

  12. 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

  13. 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.

  14. Large Cell Neuroendocrine Carcinoma of Urinary Bladder; Case Presentation

    OpenAIRE

    Ayşegül SARI; Ermete, Murat; Canan SADULLAHOĞLU; Bal, Kaan; Ahmet BOLÜKBAŞI

    2013-01-01

    Large cell neuroendocrine tumor of the urinary bladder is very rare. It is a type of neuroendocrine carcinoma that is morphologically different from small cell carcinoma.This manuscript describes a 67-year-old man who presented with hematuria. Ultrasonogrophic and computer tomography revealed a 5 cm mass in right posterolateral wall of the bladder that invaded perivesical tissue and he subsequently underwent transurethral resection. Microscopic examination showed a tumor with a sheet-like and...

  15. Ibrutinib Before and After Stem Cell Transplant in Treating Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma

    Science.gov (United States)

    2016-09-01

    Activated B-Cell-Like Diffuse Large B-Cell Lymphoma; B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma

  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. Large Cell Neuroendocrine Carcinoma of Urinary Bladder; Case Presentation

    Directory of Open Access Journals (Sweden)

    Ayşegül SARI

    2013-01-01

    Full Text Available Large cell neuroendocrine tumor of the urinary bladder is very rare. It is a type of neuroendocrine carcinoma that is morphologically different from small cell carcinoma.This manuscript describes a 67-year-old man who presented with hematuria. Ultrasonogrophic and computer tomography revealed a 5 cm mass in right posterolateral wall of the bladder that invaded perivesical tissue and he subsequently underwent transurethral resection. Microscopic examination showed a tumor with a sheet-like and trabecular growth pattern comprising necrotic areas which infiltrated the muscularis propria. Tumoral cells had coarse chromatin, prominent nucleoli, moderate amount of cytoplasm and immunohistochemically stained strongly positive with synaptophysin, chromogranin and CD56.There are only few case reports of large cell neuroendocrine tumor of the urinary bladder so the biological behavior and the treatment protocol of these tumors are still obscure. Appropriate management protocols and prognostic estimation could be achived by the increased number of cases being reported. Therefore in a case of a poorly differentiated tumor in bladder, although rare, it is important to consider large cell neuroendocrine carcinoma in differential diagnosis.

  18. 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

  19. 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

  20. Photoluminescence in large fluence radiation irradiated space silicon solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Hisamatsu, Tadashi; Kawasaki, Osamu; Matsuda, Sumio [National Space Development Agency of Japan, Tsukuba, Ibaraki (Japan). Tsukuba Space Center; Tsukamoto, Kazuyoshi

    1997-03-01

    Photoluminescence spectroscopy measurements were carried out for silicon 50{mu}m BSFR space solar cells irradiated with 1MeV electrons with a fluence exceeding 1 x 10{sup 16} e/cm{sup 2} and 10MeV protons with a fluence exceeding 1 x 10{sup 13} p/cm{sup 2}. The results were compared with the previous result performed in a relative low fluence region, and the radiation-induced defects which cause anomalous degradation of the cell performance in such large fluence regions were discussed. As far as we know, this is the first report which presents the PL measurement results at 4.2K of the large fluence radiation irradiated silicon solar cells. (author)

  1. Large area shunt defect free GaAs solar cells

    International Nuclear Information System (INIS)

    Shunt defects have been found to be the type of defect that can degrade and cause failure in GaAs solar cells. Because of their catastrophic effects, it is necessary to insure that no shunt defects are formed in the solar cell. A technique for fabricating large area shunt defect free GaAs solar cells has been investigated. A Be doped GaAlAs window layer was grown directly on a n-type GaAs substrate by isothermal liquid phase epitaxial growth (ILPE). By growing directly on the GaAs substrate and not growing the usual buffer, absorber, collector, and window layer combination, the fabrication is simplified and yields can be large. It was found that the Be from the liquid GaAlAs melt diffused into the GaAs to form a complete collector layer. Because the collector is complete, a shunt defect free solar cell is produced. The results of the ILPE growth are reported for both 5.1 cm2 and 0.12 cm2 solar cells. The technique is very versatile and may be used to fabricate larger area solar cells

  2. Large area magnetic micropallet arrays for cell colony sorting.

    Science.gov (United States)

    Cox-Muranami, Wesley A; Nelson, Edward L; Li, G P; Bachman, Mark

    2016-01-01

    A new micropallet array platform for adherent cell colony sorting has been developed. The platform consisted of thousands of square plastic pallets, 270 μm by 270 μm on each side, large enough to hold a single colony of cells. Each pallet included a magnetic core, allowing them to be collected with a magnet after being released using a microscope mounted laser system. The micropallets were patterned from 1002F epoxy resist and were fabricated on translucent, gold coated microscope slides. The gold layer was used as seed for electroplating the ferromagnetic cores within every individual pallet. The gold layer also facilitated the release of each micropallet during laser release. This array allows for individual observation, sorting and collection of isolated cell colonies for biological cell colony research. In addition to consistent release and recovery of individual colonies, we demonstrated stable biocompatibility and minimal loss in imaging quality compared to previously developed micropallet arrays. PMID:26606460

  3. Simultaneous large cell neuroendocrine carcinoma and adenocarcinoma of the stomach

    Institute of Scientific and Technical Information of China (English)

    Tadashi Terada; Hirotoshi Maruo

    2011-01-01

    A large cell neuroendocrine carcinoma (LCNEC) of the stomach is very rare. A 76-year-old Japanese man was admitted to our hospital because of epigastralgia and nausea. Endoscopy revealed 2 large tumors in the stomach. He did not have multiple endocrine neoplasia type Ⅰ or Zollinger-Ellison syndrome. Imaging modali-ties, including computed tomography and magnetic resonance imaging, revealed no other tumors. Gas-trectomy, cholecystectomy, and lymph node dissection were performed. The resected stomach had 2 tumors: one was an antral ulcerated type 3 tumor measuring 5 cm x 5 cm, and the other was a polypoid type 1 tumor measuring 6 cm x 6 cm x 3 cm in the fundus. Micro-scopically, the antral ulcerated tumor was a well differ-entiated adenocarcinoma with deep invasion. The fun-dus polypoid tumor was a LCNEC, being composed of malignant large cells arranged in trabecular and nested patterns. The tumor cells were large and the nuclei were vesicular. Nucleoli were frequently present, and there were many mitotic figures, apoptotic bodies, and necrotic areas. Much lymphovascular permeation was seen. Seven out of 29 dissected lymph nodes showed metastatic foci; 6 were from the LCNEC and 1 from the adenocarcinoma. Many intravascular tumor emboli of LCNEC were seen in the peritoneum around the lymph nodes. Mucins were present in the adenocarcinoma but not in the LCNEC. Immunohistochemically, the LCNEC tumor cells were positive for pancytokeratins, synaptophysin (50% positive), chromogranin A (10% positive), Ki-67 (90% labeled), and platelet-derived growth factor-α (80% positive). They were negative for KIT, p53, CD56, and neuron-specific enolase. The non-cancerous stomach showed a normal number of endocrine cells. The patient is now treated with adju-vant chemotherapy.

  4. Development of the large scale digital cell analysis system

    International Nuclear Information System (INIS)

    Quantitative analysis of large numbers of cells exposed to various stresses would be facilitated by an automated microscope system designed to monitor up to 1000 microscope fields over time intervals of up to one month. The Large Scale Digital Cell Analysis System (LSDCAS) was designed by the authors to provide such analysis capabilities. This report presents a description of the development of the LSDCAS and its application to the study of cells undergoing radiation-induced mitotic catastrophe. A detailed description of the data acquisition algorithms used and the hardware configuration underlying the system is presented. Quantitative analysis of colony formation of cells exposed to 5 Gy X irradiation is presented. Upon analysis, it was found that the plating efficiency in irradiated population agreed with that obtained using conventional colony-formation assays, indicating the accuracy of LSDCAS in the determination of cell clonogenicity. An unexpected finding was that fully 50% of the surviving colonies exhibited mitotic catastrophe that persisted throughout colony formation. Ongoing extension of the capabilities of the LSDCAS using image segmentation techniques applied to a variety of cellular endpoints is then briefly described. (author)

  5. Is ALK-gene rearrangement overlooked in primary gastrointestinal T-cell lymphomas? About two cases.

    Science.gov (United States)

    Mneimneh, Wadad S; Vyas, Shikhar Gautam; Cheng, Liang; Cummings, Oscar W; Czader, Magdalena

    2015-12-01

    A 41-year-old male patient with a history of ankylosing spondylitis and Crohn disease, treated with immunomodulators and disease-modifying drugs, was diagnosed with a primary intestinal T-cell lymphoma that followed a 7.5-year-course. This transmural proliferation lacked cytological characteristics of anaplastic large cell lymphoma (ALCL), and was CD8-positive, and CD30- and anaplastic lymphoma kinase (ALK)-negative by immunohistochemistry (IHC). However, ALK-gene rearrangement (ALK-gr) was detected by fluorescence in situ hybridization (FISH) in both initial and persistent disease. The possibility of indolent T-cell lymphoproliferative disease of the gastrointestinal tract with atypical features (transmural involvement) related to ALK-gr was suggested. A previous case of aggressive 'enteropathy-associated ALCL' in the context of celiac disease was recently reported, which also lacked anaplastic morphology, and where CD30 and ALK expression was incidentally demonstrated by IHC, and ALK-gr subsequently confirmed by FISH. These two recent cases represent two distinct rare entities pertaining to the group of primary intestinal T-cell lymphomas, and they both show unexpected ALK-gr. This suggests that ALK-gr has been overlooked in the group of primary intestinal T-cell lymphomas. Performing IHC and FISH tests for ALK-gr in primary gastrointestinal T-cell lymphomas might be of importance, particularly with the advancement of targeted therapy that could impact treatment and prognosis. PMID:26531107

  6. Diffuse large B-cell lymphoma of the oral cavity

    International Nuclear Information System (INIS)

    The authors report a case of diffuse large B-cell lymphoma (DLBL) of the oral cavity. The patient was a 73-year-old white man who first presented at the Division of Stomatology with a large nodular mass in the hard palate and a nodular lesion in the upper lip, which were diagnosed as DLBL. The patient was treated with eight cycles of CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine and prednisone), but the disease recurred 22 months after the end of the therapy. Both primary sites hard palate and upper lip were involved again and the patient was resubmitted to chemotherapy. (author)

  7. Residence time distribution in large industrial flotation cells

    International Nuclear Information System (INIS)

    In order to study the hydrodynamic behavior of large flotation cells, the radioactive tracer technique was used to measure the residence time distribution (RTD) of the liquid and solid in an industrial rougher flotation bank consisting of 7 cells of 130 m3. Thus, a pneumatic system of high reliability was used in order to introduce a small amount of radioactive tracer (around 100 mL of liquid or pulp) at the feed pulp entrance. Then, the time response of the radioactive tracer was measured on-line, at different points along the bank, using non-invasive sensors located directly in the discharge pipe of each cell. Activity (cps) was measured by scintillating crystal sensors of NaI(Tl) of 1'' x 1.5'' Saphymo Srat, thus allowing the simultaneous data acquisition of up to 12 control points, with a minimum period of 50 milliseconds. 82Br in solution was used as liquid tracer, while mineral gangue was used as solid non-floatable tracer. The solid tracer was also tested at three size classes (coarse: +150, intermediate: -150+45 and, fine -45 microns) in order to evaluate solids segregation. An advantage of using the radioactive tracer technique is the direct testing of the actual solid particles (similar physical and chemical properties, size distribution, shape, etc.). tracer injection is almost instantaneous, because only a small amount of radioactive tracer is required. Another advantage is its capability for on-line measurements at various points inside the system without disturbances related to process sampling. Also, the individual performance of each cell along the bank was evaluated by a series of tests performed around each cell. The RTD was measured on-line in the tailings stream of each cell. The procedure was repeated for the 7 cells of the flotation bank. From a hydrodynamic point of view, the new experimental data has confirmed that single mechanical flotation cells, of large size, can deviate significantly from perfect mixing, while in terms of process

  8. 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.

  9. Role of radiation therapy in large cell lymphoma

    International Nuclear Information System (INIS)

    This paper compares the results of treatment for large cell lymphoma with use of radiation therapy (RT), chemotherapy (CT), or both. The authors retrospectively studied 142 patients with large cell lymphoma. Seventy-two has stage I or II disease and 70, stage III or IV; 37% had B symptoms. CT was used in 66 patients, RT in 22, both in 46, and surgery with or without RT or CT in eight. CT regimens were CHOP, 38 patients; C-MOPP/COPP, 25; CHOP-bleo/BACOP, 15; COP-BLAN-MEL, 8; M-BACOD, 8; COP/CVP, 5; COP-BLAM, 5; and other regimens, 12. Statistical analysis showed that age, stage B symptoms, and treatment were significant variables determining survival. In stages I and II, the 5-year survival rate with RT plus CT was 65%; with CT, 35%; and with RT, 9% (P = < .01)

  10. Large-cell Neuroendocrine Carcinoma of the Lung: Unusual Presentation

    Directory of Open Access Journals (Sweden)

    Miguel Ángel Serra Valdés

    2014-11-01

    Full Text Available Lung cancer is the leading cause of death among malignant tumors. Pulmonary neuroendocrine tumors encompass a broad spectrum of tumors including the large-cell neuroendocrine carcinoma. The case of a 57-year-old white housewife with a history of smoking, diabetes, hypothyroidism and hypertension who sought medical attention because of headache, vomiting, weight loss, neuropsychiatric symptoms and metastatic inguinal lymphadenopathy is presented. The symptoms resulted from the extrapulmonary metastases found. Imaging studies, histology and immunohistochemistry confirmed the diagnosis of large-cell carcinoma of the lung with neuroendocrine pattern. This type of highly aggressive tumor is usually diagnosed when there are already multiple metastases, which affects the short-term prognosis. The aim of this paper is to inform the medical community of this case due to the scarce reports in the literature.

  11. Diffuse Large B Cell Lymphoma of the Breast

    OpenAIRE

    Feryal Karaca; Vehbi Ercolak; Cigdem Usul Afsar; Meral Gunaldi

    2015-01-01

    Primary breast lymphoma is rarely encountered in Non-Hodgkin Lymphomas. However, if early diagnosis is made, and treatment is started immediately in patients with low grade and stage, patient survival is increased. 39-year old female patient applied us due to a palpable mass. She was diagnosed with the Non-Hodgkin Lymphoma Diffuse Large B Cell Lymphoma after the investigations. Curative external radiotherapy was applied after 6 courses of CHOP-R chemotherapy to the patient with Stage-IIE favo...

  12. Phosphorylation of Large T Antigen Regulates Merkel Cell Polyomavirus Replication

    Energy Technology Data Exchange (ETDEWEB)

    Diaz, Jason; Wang, Xin; Tsang, Sabrina H. [Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States); Jiao, Jing [Department of Pathology and Laboratory Medicine, Children’s Hospital of Philadelphia, Philadelphia, PA 19104 (United States); You, Jianxin, E-mail: jianyou@mail.med.upenn.edu [Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States)

    2014-07-08

    Merkel Cell Polyomavirus (MCPyV) was recently discovered as a novel human polyomavirus that is associated with ~80% of Merkel Cell Carcinomas. The Large Tumor antigen (LT) is an early viral protein which has a variety of functions, including manipulation of the cell cycle and initiating viral DNA replication. Phosphorylation plays a critical regulatory role for polyomavirus LT proteins, but no investigation of MCPyV LT phosphorylation has been performed to date. In this report mass spectrometry analysis reveals three unique phosphorylation sites: T271, T297 and T299. In vivo replication assays confirm that phosphorylation of T271 does not play a role in viral replication, while modification at T297 and T299 have dramatic and opposing effects on LT’s ability to initiate replication from the viral origin. We test these mutants for their ability to bind, unwind, and act as a functional helicase at the viral origin. These studies provide a framework for understanding how phosphorylation of LT may dynamically regulate viral replication. Although the natural host cell of MCPyV has not yet been established, this work provides a foundation for understanding how LT activity is regulated and provides tools for better exploring this regulation in both natural host cells and Merkel cells.

  13. Phosphorylation of Large T Antigen Regulates Merkel Cell Polyomavirus Replication

    International Nuclear Information System (INIS)

    Merkel Cell Polyomavirus (MCPyV) was recently discovered as a novel human polyomavirus that is associated with ~80% of Merkel Cell Carcinomas. The Large Tumor antigen (LT) is an early viral protein which has a variety of functions, including manipulation of the cell cycle and initiating viral DNA replication. Phosphorylation plays a critical regulatory role for polyomavirus LT proteins, but no investigation of MCPyV LT phosphorylation has been performed to date. In this report mass spectrometry analysis reveals three unique phosphorylation sites: T271, T297 and T299. In vivo replication assays confirm that phosphorylation of T271 does not play a role in viral replication, while modification at T297 and T299 have dramatic and opposing effects on LT’s ability to initiate replication from the viral origin. We test these mutants for their ability to bind, unwind, and act as a functional helicase at the viral origin. These studies provide a framework for understanding how phosphorylation of LT may dynamically regulate viral replication. Although the natural host cell of MCPyV has not yet been established, this work provides a foundation for understanding how LT activity is regulated and provides tools for better exploring this regulation in both natural host cells and Merkel cells

  14. Clear cell variant of diffuse large B-cell lymphoma: a case report

    Directory of Open Access Journals (Sweden)

    Sahatciu-Meka Vjollca

    2011-05-01

    Full Text Available Abstract Introduction Diffuse large B-cell lymphoma is a diffuse proliferation of large neoplastic B lymphoid cells with a nuclear size equal to or exceeding the normal macrophage nuclei. We report a case of a clear cell variant of diffuse large B-cell lymphoma involving a lymph node in the neck, which was clinically suspected of being metastatic carcinoma. Case presentation A 39-year-old Caucasian ethnic Albanian man from Kosovo presented with a rapidly enlarging lymph node in his neck, but he also disclosed B symptoms and fatigue. A cytological aspirate of the lymph node revealed pleomorphic features. Our patient underwent a cervical lymph node biopsy (large excision. The mass was homogeneously fish-flesh, pale white tissue replacing almost the whole structure of the lymph node. The lymph node biopsy showed a partial alveolar growth pattern, which raised clinical suspicion that it was an epithelial neoplasm. With regard to morphological and phenotypic features, we discovered large nodules in diffuse areas, comprising large cells with slightly irregular nuclei and clear cytoplasm admixed with a few mononuclear cells. In these areas, there was high mitotic activity, and in some areas there were macrophages with tangible bodies. Staining for cytokeratins was negative. These areas had the following phenotypes: cluster designation marker 20 (CD20 positive, B-cell lymphoma (Bcl-2-positive, Bcl-6-, CD5-, CD3-, CD21+ (in alveolar patterns, prostate-specific antigen-negative, human melanoma black marker 45-negative, melanoma marker-negative, cytokeratin-7-negative and multiple myeloma marker 1-positive in about 30% of cells, and exhibited a high proliferation index marker (Ki-67, 80%. Conclusion According to the immunohistochemical findings, we concluded that this patient has a clear cell variant of diffuse large B-cell lymphoma of activated cell type, post-germinal center cell origin. Our patient is undergoing R-CHOP chemotherapy treatment.

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

    Science.gov (United States)

    2013-01-15

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Central Nervous System Germ Cell Tumor; Adult Choroid Plexus Tumor; Adult Craniopharyngioma; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade I Meningioma; Adult Grade II Meningioma; Adult Grade III Meningioma; Adult Medulloblastoma; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Pilocytic Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Subependymoma; Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Meningeal Melanocytoma

  16. Large-scale generation of cell-derived nanovesicles

    Science.gov (United States)

    Jo, W.; Kim, J.; Yoon, J.; Jeong, D.; Cho, S.; Jeong, H.; Yoon, Y. J.; Kim, S. C.; Gho, Y. S.; Park, J.

    2014-09-01

    Exosomes are enclosed compartments that are released from cells and that can transport biological contents for the purpose of intercellular communications. Research into exosomes is hindered by their rarity. In this article, we introduce a device that uses centrifugal force and a filter with micro-sized pores to generate a large quantity of cell-derived nanovesicles. The device has a simple polycarbonate structure to hold the filter, and operates in a common centrifuge. Nanovesicles are similar in size and membrane structure to exosomes. Nanovesicles contain intracellular RNAs ranging from microRNA to mRNA, intracellular proteins, and plasma membrane proteins. The quantity of nanovesicles produced using the device is 250 times the quantity of naturally secreted exosomes. Also, the quantity of intracellular contents in nanovesicles is twice that in exosomes. Nanovesicles generated from murine embryonic stem cells can transfer RNAs to target cells. Therefore, this novel device and the nanovesicles that it generates are expected to be used in exosome-related research, and can be applied in various applications such as drug delivery and cell-based therapy.

  17. The importance of Notch signaling in peripheral T-cell lymphomas

    DEFF Research Database (Denmark)

    Kamstrup, Maria Rørbæk; Biskup, Edyta; Gjerdrum, Lise Mette Rahbek;

    2014-01-01

    Peripheral T-cell lymphomas (PTLs) represent an area of high medical need. Previously, we demonstrated high expression of Notch, a known oncogene, in primary cutaneous anaplastic large cell lymphoma (ALCL). In this study, we performed immunohistochemical staining for Notch1 in lymph nodes from PTL...... ALK- (nine cases) (p > 0.05). In the ALK+ ALCL cell line, Karpas-299, pharmacological inhibition of Notch with γ-secretase inhibitor (GSI) I was far more potent than with GSI IX, XX and XXI with regard to cell viability and apoptosis. In conclusion, PTL tumor cells have prominent Notch1 expression and...

  18. 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。

  19. 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

  20. Dominant neurologic symptomatology in intravascular large B-cell lymphoma.

    Science.gov (United States)

    Kubisova, K; Martanovic, P; Sisovsky, V; Tomleinova, Z; Steno, A; Janega, P; Rychly, B; Babal, P

    2016-01-01

    Intravascular large B-cell lymphoma (IVLBCL) is a rare variant of extranodal large B-cell lymphoma and it is characterized by selective intravascular proliferation of malignant cells. Typical features of the disease include aggressive behavior, rapid and frequently fatal course. Clinical picture is non-specific and heterogeneous, depending on the affected organ. It is not uncommon that this unique type of lymphoma is diagnosed post mortem. Herein, we report two cases of IVLBCL with neurologic symptomatology. In our clinical study patient 1 was an 80-year-old male with mixed paraparesis of lower extremities and difficulties with sphincter control. Patient 2 (56-year-old male) had vision malfunction, mental status changes and defect in phatic and motor functions. In both cases definite diagnosis was established by histological examination of necroptic material. We propose to include IVLBCL in differential diagnostic considerations in patients presenting with gradually impairing neurological status and spinal cord damage of unknown etiology (Fig. 2, Ref. 9). PMID:27546361

  1. Intravascular Large B-Cell Lymphoma: A Difficult Diagnostic Challenge.

    Science.gov (United States)

    Khan, Maria S; McCubbin, Mark; Nand, Sucha

    2014-01-01

    Case Presentation. A 69-year-old Hispanic male, with a past history of diabetes and coronary disease, was admitted for fever, diarrhea, and confusion of 4 weeks duration. Physical examination showed a disoriented patient with multiple ecchymoses, possible ascites, and bilateral scrotal swelling. Hemoglobin was 6.7, prothrombin time (PT) 21.4 seconds with international normalized ratio 2.1, partial thromboplastin time (PTT) 55.6 seconds, fibrin split 10 µg/L, and lactate dehydrogenase (LDH) 1231 IU/L. Except for a positive DNA test for Epstein-Barr virus (EBV) infection, extensive diagnostic workup for infections, malignancy, or a neurological cause was negative. Mixing studies revealed a nonspecific inhibitor of PT and PTT but Factor VIII levels were normal. The patient was empirically treated with antibiotics but developed hypotension and died on day 27 of admission. At autopsy, patient was found to have intravascular diffuse large B-cell lymphoma involving skin, testes, lung, and muscles. The malignant cells were positive for CD20, CD791, Mum-1, and Pax-5 and negative for CD3, CD5, CD10, CD30, and Bcl-6. The malignant cells were 100% positive for Ki-67. Discussion. Intravascular large cell B-cell lymphoma (IVLBCL) is rare form of diffuse large B-cell lymphoma and tends to proliferate within small blood vessels, particularly capillaries and postcapillary venules. The cause of its affinity for vascular bed remains unknown. In many reports, IVLBCL was associated with HIV, HHV8, and EBV infections. The fact that our case showed evidence of EBV infection lends support to the association of this diagnosis to viral illness. The available literature on this subject is scant, and in many cases, the diagnosis was made only at autopsy. The typical presentation of this disorder is with B symptoms, progressive neurologic deficits, and skin findings. Bone marrow, spleen, and liver are involved in a minority of patients. Nearly all patients have elevated LDH, and about 65% are

  2. 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。

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Performance model for large area solid oxide fuel cells

    Science.gov (United States)

    Klotz, Dino; Schmidt, Jan Philipp; Weber, André; Ivers-Tiffée, Ellen

    2014-08-01

    A parameter set obtained from a 1 cm2 size electrode cell is used to develop and calibrate a one-dimensional spatially resolved model. It is demonstrated that this performance model precalculates the evolving operating parameters along the gas channel of a large-sized cell. Input parameters are: (i) number of discretization elements N, accounting for anodic gas conversion, (ii) anodic gas flow rate and composition and (iv) operating voltage. The model calculations based on data from the 1 cm2 cell are scaled to be equivalent to a larger cell with 16 cm2 electrode size which is used to validate the performance model. The current/voltage characteristics can be predicted very accurately, even when anodic gas flow rates vary by as much as a factor of four. The performance model presented herein simulates the total overvoltage and does so in a broad range of operation conditions. This is done with an accuracy of the simulated current better than 6.1% for UOP = 0.85 V, 3.8% for UOP = 0.8 V and 3.7% for UOP = 0.75 V. It is hoped that these equations will form the basis of a greater model, capable of predicting all the conditions found throughout any industrial stack.

  5. New model for gastroenteropancreatic large-cell neuroendocrine carcinoma: establishment of two clinically relevant cell lines.

    Directory of Open Access Journals (Sweden)

    Andreas Krieg

    Full Text Available Recently, a novel WHO-classification has been introduced that divided gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN according to their proliferation index into G1- or G2-neuroendocrine tumors (NET and poorly differentiated small-cell or large-cell G3-neuroendocrine carcinomas (NEC. Our knowledge on primary NECs of the GEP-system is limited due to the rarity of these tumors and chemotherapeutic concepts of highly aggressive NEC do not provide convincing results. The aim of this study was to establish a reliable cell line model for NEC that could be helpful in identifying novel druggable molecular targets. Cell lines were established from liver (NEC-DUE1 or lymph node metastases (NEC-DUE2 from large cell NECs of the gastroesophageal junction and the large intestine, respectively. Morphological characteristics and expression of neuroendocrine markers were extensively analyzed. Chromosomal aberrations were mapped by array comparative genomic hybridization and DNA profiling was analyzed by DNA fingerprinting. In vitro and in vivo tumorigenicity was evaluated and the sensitivity against chemotherapeutic agents assessed. Both cell lines exhibited typical morphological and molecular features of large cell NEC. In vitro and in vivo experiments demonstrated that both cell lines retained their malignant properties. Whereas NEC-DUE1 and -DUE2 were resistant to chemotherapeutic drugs such as cisplatin, etoposide and oxaliplatin, a high sensitivity to 5-fluorouracil was observed for the NEC-DUE1 cell line. Taken together, we established and characterized the first GEP large-cell NEC cell lines that might serve as a helpful tool not only to understand the biology of these tumors, but also to establish novel targeted therapies in a preclinical setup.

  6. Large volume high-pressure cell for inelastic neutron scattering.

    Science.gov (United States)

    Wang, W; Sokolov, D A; Huxley, A D; Kamenev, K V

    2011-07-01

    Inelastic neutron scattering measurements typically require two orders of magnitude longer data collection times and larger sample sizes than neutron diffraction studies. Inelastic neutron scattering measurements on pressurised samples are particularly challenging since standard high-pressure apparatus restricts sample volume, attenuates the incident and scattered beams, and contributes background scattering. Here, we present the design of a large volume two-layered piston-cylinder pressure cell with optimised transmission for inelastic neutron scattering experiments. The design and the materials selected for the construction of the cell enable its safe use to a pressure of 1.8 GPa with a sample volume in excess of 400 mm(3). The design of the piston seal eliminates the need for a sample container, thus providing a larger sample volume and reduced absorption. The integrated electrical plug with a manganin pressure gauge offers an accurate measurement of pressure over the whole range of operational temperatures. The performance of the cell is demonstrated by an inelastic neutron scattering study of UGe(2). PMID:21806195

  7. Hemophagocytic lymphohistiocytosis secondary to T-cell/histiocyte-rich large B-cell lymphoma

    Directory of Open Access Journals (Sweden)

    Katherine Devitt

    2014-01-01

    Full Text Available Hemophagocytic lymphohistiocytosis (HLH is a life-threatening clinical syndrome characterized by dysregulation of the immune system. Impaired function of cytotoxic T cells and natural killer cells is often seen, and T-cell malignancies represent most cases of lymphoma-associated HLH. HLH associated with B-cell lymphoma is rare. We describe a case of a 30-year-old man who presented with fever, splenomegaly, and hyperferritinemia. Bone marrow biopsy revealed T-cell/histiocyte-rich large B-cell lymphoma, a rare, aggressive B-cell malignancy. This case highlights the interplay between a pro-inflammatory cytokine microenvironment and tumor-mediated immune suppression, and addresses the importance of accurately diagnosing these entities for appropriate clinical management.

  8. Carfilzomib, Rituximab, Ifosfamide, Carboplatin, and Etoposide in Treating Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma

    Science.gov (United States)

    2016-02-16

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

  9. 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

  10. 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)

  11. 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

  12. Fludarabine Phosphate, Low-Dose Total-Body Irradiation, and Donor Stem Cell Transplant Followed by Cyclosporine, Mycophenolate Mofetil, Donor Lymphocyte Infusion in Treating Patients With Hematopoietic Cancer

    Science.gov (United States)

    2016-08-01

    Acute Undifferentiated Leukemia; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Childhood Burkitt Lymphoma; Childhood Diffuse Large Cell Lymphoma; Childhood Grade III Lymphomatoid Granulomatosis; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Myelomonocytic Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Juvenile Myelomonocytic Leukemia; Mast Cell Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Myeloid/NK-cell Acute Leukemia; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Primary Systemic Amyloidosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma

  13. R-ICE and Lenalidomide in Treating Patients With First-Relapse/Primary Refractory Diffuse Large B-Cell Lymphoma

    Science.gov (United States)

    2015-12-30

    Diffuse Large B-Cell Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Transformed Recurrent Non-Hodgkin Lymphoma

  14. Diffuse Large B Cell Lymphoma of the Breast

    Directory of Open Access Journals (Sweden)

    Feryal Karaca

    2015-03-01

    Full Text Available Primary breast lymphoma is rarely encountered in Non-Hodgkin Lymphomas. However, if early diagnosis is made, and treatment is started immediately in patients with low grade and stage, patient survival is increased. 39-year old female patient applied us due to a palpable mass. She was diagnosed with the Non-Hodgkin Lymphoma Diffuse Large B Cell Lymphoma after the investigations. Curative external radiotherapy was applied after 6 courses of CHOP-R chemotherapy to the patient with Stage-IIE favorable, and B symptoms. After 48-month follow up, patient follow up is being continued without any progression, or recurrence or metastasis. [Cukurova Med J 2015; 40(1.000: 151-157

  15. Dose Monitoring of Busulfan and Combination Chemotherapy in Hodgkin or Non-Hodgkin Lymphoma Undergoing Stem Cell Transplant

    Science.gov (United States)

    2015-08-12

    Adult Grade III Lymphomatoid Granulomatosis; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Childhood Burkitt Lymphoma; Childhood Diffuse Large Cell Lymphoma; Childhood Grade III Lymphomatoid Granulomatosis; Childhood Immunoblastic Large Cell Lymphoma; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Contiguous Stage II Adult Burkitt Lymphoma; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Contiguous Stage II Adult Lymphoblastic Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult

  16. Role of stem cells in large bowel carcinogenesis

    Directory of Open Access Journals (Sweden)

    N. A. Nefedova

    2015-10-01

    Full Text Available Сancer stem cells (CSC play a significant role in the development and progression of colorectal cancer. They are capable of self-senewal and multipotent differentiation. CSC can be formed from stem cells or mutant by dedifferentiation of crypt epithelial cells. Recently, much attention is paid to CSC in colon cancer, but very little has been published regarding their expression in colon polyps. In 2010 The World Health Organization attributed the so-called serrated lesions, including hyperplastic polyp, serrated sessile adenoma and traditional serrated adenoma to a group of precancerous lesions of the colon in addition to the classical tubular, villous and tubulo-villous adenomas. Despite the large number of publications devoted to the newly selected category, a full understanding of the processes involved in the formation of polyps and their progression into colon cancer, there is still no. Identification of CSC in colon polyps will assess their potential malignancy conduct adequate therapy, determine the amount of the operation and further treatment strategy. This in turn will contribute to the early detection and prevention of cancer. Identification of CSC, an assessment of their localization and distribution in tubular adenomas, serrated adenoma broad-based, traditional serrated adenoma and hyperplastic polyps allow to evaluate the potential of malignancy and prognosis for each of the polyps. In this regard, the definition of markers characteristic of colon CSC, is interesting not only from a scientific, but also from a practical point of view.

  17. 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.

  18. 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

  19. Diffuse large B-cell lymphoma in patient after treatment of angioimmunoblastic T-cell lymphoma.

    Science.gov (United States)

    Skugor, Nives Dzeko; Perić, Zinaida; Vrhovac, Radovan; Radić-Kristo, Delfa; Kardum-Skelin, Ika; Jaksić, Branimir

    2010-03-01

    Relatively few cases of Epstein-Barr (EBV)-positive B-cell lymphomas arising in patients with angioimmunoblastic T-cell lymphoma (AITL) have been reported. We report a case of AITL in which diffuse large B-cell lymphoma arose 13 months after the initial diagnosis of AITL. In a 36-year-old female patient, evaluated for moderate leukocytosis, peripheral and abdominal lymphadenopathy AITL was diagnosed in March 2008, based on results of fine-needle aspiration cytology (FNAC) of the enlarged cervical and supraclavicular lymph nodes. The diagnosis was also confirmed by immunophenotyping and histopathology of the cervical lymph nodes. The patient initially recieved FED chemotherapy (fludarabine, cyclophosphamide, dexamethasone) followed by elective autologous hematopoietic stem cell transplantation. In April 2009 the patient was hospitalized because of fever, pancytopenia, hyperbilirubinemia and peripheral lymphadenopathy. The FNAC of the enlarged cervical lymph nodes was performed again, but this time the smears were composed of polymorphous population of lymphocytes with the predomination of large cells, CD20+ on immunocytochemical stains. The immunophenotyping confirmed a predomination of monoclonal mature B-cells. Patient had high number of EBV DNA copies in plasma and serologic testing revealed increased titers of EBV VCA IgG and EBV EBNA IgG. CHOP-R chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab) was then administered, resulting in good partial response of the disease. Reduced intensity allogeneic stem cell transplantation performed thereafter, resulted in complete remission of the disease. AITL is a rare lymphoproliferative disorder in which the neoplastic T-cells represent the minority of the lymph node cell population and almost all cases harbor EBV-infected B-cells. Various authors postulated that immunodeficiency in AITL patients together with immunosuppressive effects of cytotoxic drugs, may be responsible for EBV

  20. Glioma Associated Oncogene Homologue 3 (GLI3), a Hedgehog Transcription Factor, is Highly Expressed in Hodgkin and Reed-Sternberg Cells of Classical Hodgkin Lymphoma

    OpenAIRE

    Greaves, Wesley O.; Kim, Ji Eun; Singh, Rajesh R.; Drakos, Elias; Kunkalla, Kranthi; Sánchez-Espiridón, Beatriz; Garcia, Juan F.; Medeiros, L. Jeffrey; Vega, Francisco

    2011-01-01

    The hedgehog signaling pathway has been shown to play a pathogenic role in diffuse large B-cell lymphoma and anaplastic large cell lymphoma, but has not been assessed in classical Hodgkin lymphoma. GLI1, GLI2, and GLI3 are transcriptional effectors of the hedgehog pathway. In this study, we first used real-time quantitative PCR to investigate expression of GLI1, GLI2, and GLI3 in 3 classical Hodgkin lymphoma cell lines. GLI1 and GLI2 were variably expressed, but GLI3 was highly expressed in a...

  1. Primary cardiac diffuse large B-cell lymphoma with activated B-cell-like phenotype

    Directory of Open Access Journals (Sweden)

    Vijaya Gadage

    2011-01-01

    Full Text Available Primary cardiac lymphoma (PCL is a rare and fatal disorder. It may often mimic other common cardiac tumors like cardiac myxoma because of similarities in the clinical presentation. We report a case of PCL of diffuse large B-cell type, in a 38-year-old, immunocompetent male who presented with superior vena cava syndrome that was excised as a myxoma. Histology revealed a large cell population diffusely and strongly expressing CD45, CD20, MUM1/IRF4 and FOXP1 hinting at an activated B-cell (ABC-like phenotype. After four cycles of Rituximab with CHOP (cyclophosphamide, hydroxydaunorubicin, Oncovin, and prednisolone the tumor regressed completely but the patient had a relapse and subsequently succumbed to the disease confirming the aggressive nature. The aggressive behavior of PCL may be possibly linked to its ABC-like origin.

  2. Multifocal Extranodal Involvement of Diffuse Large B-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Devrim Cabuk

    2013-01-01

    Full Text Available Endobronchial involvement of extrapulmonary malignant tumors is uncommon and mostly associated with breast, kidney, colon, and rectum carcinomas. A 68-year-old male with a prior diagnosis of colon non-Hodgkin lymphoma (NHL was admitted to the hospital with a complaint of cough, sputum, and dyspnea. The chest radiograph showed right hilar enlargement and opacity at the right middle zone suggestive of a mass lesion. Computed tomography of thorax revealed a right-sided mass lesion extending to thoracic wall with the destruction of the third and the fourth ribs and a right hilar mass lesion. Fiberoptic bronchoscopy was performed in order to evaluate endobronchial involvement and showed stenosis with mucosal tumor infiltration in right upper lobe bronchus. The pathological examination of bronchoscopic biopsy specimen reported diffuse large B-cell lymphoma and the patient was accepted as the endobronchial recurrence of sigmoid colon NHL. The patient is still under treatment of R-ICE (rituximab-ifosfamide-carboplatin-etoposide chemotherapy and partial regression of pulmonary lesions was noted after 3 courses of treatment.

  3. Primary Mediastinal Large B-Cell Lymphoma during Pregnancy

    Directory of Open Access Journals (Sweden)

    Cesar A. Perez

    2012-01-01

    Full Text Available Non-Hodgkin’s Lymphoma (NHL rarely presents during pregnancy and primary mediastinal large B-cell lymphoma (PMLBCL accounts for approximately 2.5% of patients with NHL. The case of a 22-year-old woman who was diagnosed with Stage IIA PMLBCL during week 13 of her intrauterine pregnancy is described. The staging consisted in computed tomography (CT of the chest and magnetic resonance imaging (MRI of the abdomen and pelvis. She was managed with R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone for a total of six cycles and, because of the early presentation during the second trimester, she received the entire chemotherapy course during the pregnancy. She delivered a healthy baby at 34 weeks of pregnancy and a 18FDG-PET/CT scan demonstrated complete remission after delivery. After 20 months of follow up she remains with no evidence of disease and her 1-year-old son has shown no developmental delays or physical abnormalities. PMLBCL, although an uncommon subgroup of DLBCL, may present during pregnancy and R-CHOP should be considered as one suitable option in this complex scenario.

  4. Alemtuzumab, Fludarabine Phosphate, and Total-Body Irradiation Followed by Cyclosporine and Mycophenolate Mofetil in Treating Patients Who Are Undergoing Donor Stem Cell Transplant for Hematologic Cancer

    Science.gov (United States)

    2016-06-13

    Acute Undifferentiated Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Juvenile Myelomonocytic Leukemia; Mast Cell Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell

  5. 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...

  6. Smooth muscle cells largely develop independently of functional hemogenic endothelium

    Directory of Open Access Journals (Sweden)

    Monika Stefanska

    2014-01-01

    Full Text Available Vascular smooth muscle cells represent a major component of the cardiovascular system. In vitro studies have shown that FLK1+ cells derived from embryonic stem (ES cells can differentiate into both endothelial and smooth muscle cells. These FLK1+ cells also contain a mesodermal precursor, the hemangioblast, able to produce endothelial, blood and smooth muscle cells. The generation of blood precursors from the hemangioblast was recently shown to occur through a transient cell population of specialised endothelium, a hemogenic endothelium. To date, the lineage relationship between this cell population and smooth muscle cell progenitors has not been investigated. In this study, we generated a reporter ES cell line in which expression of the fluorescent protein H2B-VENUS is driven by the α-smooth muscle actin (α-SMA regulatory sequences. We demonstrated that this reporter cell line efficiently trace smooth muscle development during ES cell differentiation. Although some smooth muscle cells are associated with broad endothelial development, we established that smooth muscle cells are mostly generated independently from a specialised functional hemogenic endothelium. This study provides new and important insights into hematopoietic and vascular development, which may help in driving further progress towards the development of bioengineered vascular grafts for regenerative medicine.

  7. Mycophenolate Mofetil and Cyclosporine in Reducing Graft-Versus-Host Disease in Patients With Hematologic Malignancies or Metastatic Kidney Cancer Undergoing Donor Stem Cell Transplant

    Science.gov (United States)

    2016-03-01

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Grade III Lymphomatoid Granulomatosis; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Grade III Lymphomatoid Granulomatosis; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Childhood Renal Cell Carcinoma; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Clear Cell Renal Cell Carcinoma; Contiguous Stage II Adult Burkitt Lymphoma; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Contiguous Stage II Adult Lymphoblastic Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Juvenile Myelomonocytic Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell

  8. Equipment for large-scale mammalian cell culture.

    Science.gov (United States)

    Ozturk, Sadettin S

    2014-01-01

    This chapter provides information on commonly used equipment in industrial mammalian cell culture, with an emphasis on bioreactors. The actual equipment used in the cell culture process can vary from one company to another, but the main steps remain the same. The process involves expansion of cells in seed train and inoculation train processes followed by cultivation of cells in a production bioreactor. Process and equipment options for each stage of the cell culture process are introduced and examples are provided. Finally, the use of disposables during seed train and cell culture production is discussed. PMID:24429549

  9. Large Scale Production of Stem Cells and Their Derivatives

    Science.gov (United States)

    Zweigerdt, Robert

    Stem cells have been envisioned to become an unlimited cell source for regenerative medicine. Notably, the interest in stem cells lies beyond direct therapeutic applications. They might also provide a previously unavailable source of valuable human cell types for screening platforms, which might facilitate the development of more efficient and safer drugs. The heterogeneity of stem cell types as well as the numerous areas of application suggests that differential processes are mandatory for their in vitro culture. Many of the envisioned applications would require the production of a high number of stem cells and their derivatives in scalable, well-defined and potentially clinical compliant manner under current good manufacturing practice (cGMP). In this review we provide an overview on recent strategies to develop bioprocesses for the expansion, differentiation and enrichment of stem cells and their progenies, presenting examples for adult and embryonic stem cells alike.

  10. Robot Work Platform for Large Hot Cell Deactivation

    Energy Technology Data Exchange (ETDEWEB)

    BITTEN, E.J.

    2000-05-01

    The 324 Building, located at the Hanford Site near Richland, Washington, is being deactivated to meet state and federal cleanup commitments. The facility is currently in its third year of a nine-year project to complete deactivation and closure for long-term surveillance and maintenance. The 324 building contains large hot cells that were used for high-radiation, high-contamination chemical process development and demonstrations. A major obstacle for the 324 deactivation project is the inability to effectively perform deactivation tasks within highly radioactive, contaminated environments. Current strategies use inefficient, resource intensive technologies that significantly impact the cost and schedule for deactivation. To meet mandated cleanup commitments, there is a need to deploy rapid, more efficient remote/robot technologies to minimize worker exposure, accelerate work tasks, and eliminate the need for multiple specialized tool design and procurement efforts. This paper describes the functions and performance requirements for a crane-deployed remote/robot Work Platform possessing full access capabilities. The remote/robot Work Platform will deploy commercially available off-the-shelf tools and end effectors to support Project cleanup goals and reduce overall project risk and cost. The intent of this system is to maximize the use of off-the-shelf technologies that minimize additional new, unproven, or novel designs. This paper further describes procurement strategy, the selection process, the selected technology, and the current status of the procurement and lessons learned. Funding, in part, has been provided by the US Department of Energy, Office of Science and Technology, Deactivation and Decommissioning Focus Area.

  11. Robot Work Platform for Large Hot Cell Deactivation

    International Nuclear Information System (INIS)

    The 324 Building, located at the Hanford Site near Richland, Washington, is being deactivated to meet state and federal cleanup commitments. The facility is currently in its third year of a nine-year project to complete deactivation and closure for long-term surveillance and maintenance. The 324 building contains large hot cells that were used for high-radiation, high-contamination chemical process development and demonstrations. A major obstacle for the 324 deactivation project is the inability to effectively perform deactivation tasks within highly radioactive, contaminated environments. Current strategies use inefficient, resource intensive technologies that significantly impact the cost and schedule for deactivation. To meet mandated cleanup commitments, there is a need to deploy rapid, more efficient remote/robot technologies to minimize worker exposure, accelerate work tasks, and eliminate the need for multiple specialized tool design and procurement efforts. This paper describes the functions and performance requirements for a crane-deployed remote/robot Work Platform possessing full access capabilities. The remote/robot Work Platform will deploy commercially available off-the-shelf tools and end effectors to support Project cleanup goals and reduce overall project risk and cost. The intent of this system is to maximize the use of off-the-shelf technologies that minimize additional new, unproven, or novel designs. This paper further describes procurement strategy, the selection process, the selected technology, and the current status of the procurement and lessons learned. Funding, in part, has been provided by the US Department of Energy, Office of Science and Technology, Deactivation and Decommissioning Focus Area

  12. 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)

  13. 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 ...

  14. 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

  15. 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.

  16. 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...

  17. 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.

  18. FOXP3 positive regulatory T-cells in cutaneous and systemic CD30 positive T-cell lymphoproliferations

    DEFF Research Database (Denmark)

    Gjerdrum, Lise Mette; Woetmann, Anders; Ødum, Niels;

    2008-01-01

    -cells (Tregs) may be implicated. In this study, skin biopsies from lymphomatoid papulosis (LyP) (n = 14), primary cutaneous anaplastic large cells lymphoma (C-ALCL) (n = 13) and systemic anaplastic large cells lymphoma (S-ALCL) with (n = 9) or without (n = 6) ALK expression were examined by immunohistology for...... FOXP3 expression in tumour cells and tumour infiltrating Tregs. Labelling of a majority of the neoplastic cells was seen in one case of C-ALCL. Another three cases (one LyP and two C-ALCL) displayed weak labelling of very occasional atypical T-cells. In the remaining 38 cases the atypical lymphoid...... infiltrate was FOXP3 negative. By contrast, all biopsies contained tumour infiltrating FOXP3-positive Tregs. Significant higher numbers were recorded in ALK negative S-ALCL and LyP than in C-ALCL and S-ALCL positive for ALK. In conclusion, it is shown that FOXP3 expression in cutaneous and systemic CD30...

  19. 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

  20. 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.

  1. Large scale spontaneous synchronization of cell cycles in amoebae

    Science.gov (United States)

    Segota, Igor; Boulet, Laurent; Franck, Carl

    2014-03-01

    Unicellular eukaryotic amoebae Dictyostelium discoideum are generally believed to grow in their vegetative state as single cells until starvation, when their collective aspect emerges and they differentiate to form a multicellular slime mold. While major efforts continue to be aimed at their starvation-induced social aspect, our understanding of population dynamics and cell cycle in the vegetative growth phase has remained incomplete. We show that substrate-growtn cell populations spontaneously synchronize their cell cycles within several hours. These collective population-wide cell cycle oscillations span millimeter length scales and can be completely suppressed by washing away putative cell-secreted signals, implying signaling by means of a diffusible growth factor or mitogen. These observations give strong evidence for collective proliferation behavior in the vegetative state and provide opportunities for synchronization theories beyond classic Kuramoto models.

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

    Science.gov (United States)

    2016-03-01

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

  3. Photothermal nanoblade for large cargo delivery into mammalian cells

    OpenAIRE

    Wu, Ting-Hsiang; Teslaa, Tara; Kalim, Sheraz; French, Christopher T; Maghadam, Shahriar; Wall, Randolph; Miller, Jeffery F.; Witte, Owen N.; Teitell, Michael A.; Chiou, Pei-Yu

    2011-01-01

    It is difficult to achieve controlled cutting of elastic, mechanically fragile, and rapidly resealing mammalian cell membranes. Here, we report a photothermal nanoblade that utilizes a metallic nanostructure to harvest short laser pulse energy and convert it into a highly localized explosive vapor bubble, which rapidly punctures a lightly-contacting cell membrane via high-speed fluidic flows and induced transient shear stress. The cavitation bubble pattern is controlled by the metallic struct...

  4. Preliminary study of steep pulse irreversible electroporation technology in human large cell lung cancer cell lines L9981

    Directory of Open Access Journals (Sweden)

    Song Zuoqing

    2013-01-01

    Full Text Available Our aim was to validate the effectiveness of steep pulse irreversible electroporation technology in human large cell lung cancer cells and to screen the optimal treatment of parameters for human large cell lung cancer cells. Three different sets of steep pulse therapy parameters were applied on the lung cancer cell line L9981. The cell line L9981 inhibition rate and proliferation capacity were detected by Vi-Cell vitality analysis and MTT. Steep pulsed irreversible electroporation technology for large cell lung cancer L9981 presents killing effects with various therapy parameters. The optimal treatment parameters are at a voltage amplitude of 2000V/cm, pulse width of 100μs, pulse frequency of 1 Hz, pulse number 10. With this group of parameters, steep pulse could have the best tumor cell-killing effects.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

  7. Donor T Cells After Donor Stem Cell Transplant in Treating Patients With Hematologic Malignancies

    Science.gov (United States)

    2016-07-20

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Blastic Phase Chronic Myelogenous Leukemia; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Phase Chronic Myelogenous Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood

  8. Development of Micromorph Cells in Large-Area Industrial Reactor

    OpenAIRE

    Wyrsch, N; Billet, A.; Bugnon, G.; Despeisse, M; Feltrin, A.; Meillaud, F.; Parascandolo, G; Ballif, C.

    2009-01-01

    The influences of the deposition pressure and silane depletion on the efficiency of single-junction microcrystalline silicon solar cells has been investigated. The efficiency is found to correlate with the ion energy which affects the density of states in the absorber material. Cell with efficiency of 7.3% at a deposition rate of 1 nm/s, and, respectively, 7.8% at 0.35 nm/s were deposited in R&D KAI M industrial reactor. Silicon oxide based intermediate reflector layers were developed in KAI ...

  9. Large and small cells non-keratinizing epidermoid vaginal carcinoma

    International Nuclear Information System (INIS)

    Five case reports of patients who were assisted at the cervix Pathology Department from 'Mariana Grajales Coello' Provincial Gynecological Obstetrical Hospital in Santiago de Cuba due to vaginal bleeding, low abdominal pain, leukorrhea and vaginal injuries are presented. The pathological study confirmed the diagnosis of squamous or epidermoid cells carcinoma

  10. Large-area nanoimprint and application to cell cultivation

    Science.gov (United States)

    Miyauchi, Akihiro; Kuwabara, Kosuke; Hasegawa, Mitsuru; Ogino, Masahiko

    2016-04-01

    Nanoimprint has been expanding to various industrial fields, such as optical device, semiconductor and bio-devices. High-throughput machine and process are necessary for industrialization of thermal nanoimprint products. Conventional parallel press method needs long tact time because of the long heating and cooling process in thermal nanoimprint. We proposed the sheet nanoimprint method which uses the newly developed belt nanomold. The continuous process became possible by using the belt nanomold and we demonstrated the 200- and 25-nm dots formation onto over 10-m-long films with 10-mm/s film speed. For bio-application, we demonstrated the spheroid formation of HeLa and hepatic cells on nanoimprinted pillar structures. The cells were easy to coalesce on the pillar structure and the spheroids were formed. Uniform-size spheroids were formed at predefined positions by using micro-incubator structure.

  11. Electrochemical cells for medium- and large-scale energy storage

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Wei; Wei, Xiaoliang; Choi, Daiwon; Lu, Xiaochuan; Yang, G.; Sun, C.

    2014-12-12

    This is one of the chapters in the book titled “Advances in batteries for large- and medium-scale energy storage: Applications in power systems and electric vehicles” that will be published by the Woodhead Publishing Limited. The chapter discusses the basic electrochemical fundamentals of electrochemical energy storage devices with a focus on the rechargeable batteries. Several practical secondary battery systems are also discussed as examples

  12. Development of large scale internal reforming molten carbonate fuel cell

    Energy Technology Data Exchange (ETDEWEB)

    Sasaki, A.; Shinoki, T.; Matsumura, M. [Mitsubishi Electric Corp., Hyogo (Japan)

    1996-12-31

    Internal Reforming (IR) is a prominent scheme for Molten Carbonate Fuel Cell (MCFC) power generating systems in order to get high efficiency i.e. 55-60% as based on the Higher Heating Value (HHV) and compact configuration. The Advanced Internal Reforming (AIR) technology has been developed based on two types of the IR-MCFC technology i.e. Direct Internal Reforming (DIR) and Indirect Internal Reforming (DIR).

  13. Design of large aperture 500 MHz 5-cell superconducting cavity

    International Nuclear Information System (INIS)

    With the potential application of Energy Recovery Linac (ERL), the superconducting (SC) cavities were developed to deliver much higher current than before. Nowadays, the current of the international SC accelerator designed has already exceeded 100 mA. This paper presents the design of a new 500 MHz 5-cell SC cavity (SINAP 5-cell cavity), in which the parameters r/Q= 515.5 Ω of the fundamental mode and the geometry factor G=275.8 are under an acceptable Radio Frequency (RF) field level. (Bpeak/Eacc=4.31 mT/MV/m and Epeak/Eacc=2.48). This design employs a larger beam pipe to propagate the Higher Order Modes (HOMs) out of the cavity and increases the damping efficiently for the dangerous HOMs. By simulation technique, it has been found that almost all the dangerous HOMs (including TE111, TM110, and TM011) can be propagated into the beam pipe and are absorbed by ferrite absorbers, when the beam pile is enlarged. Finally, the loss factor for the new 5-cell cavity is also calculated. (authors)

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. 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.)

  19. 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.

  20. Affinity-purified interleukin 2 induces proliferation of large but not small B cells.

    OpenAIRE

    Mond, J J; C. Thompson; Finkelman, F.D.; Farrar, J.; Schaefer, M.; Robb, R J

    1985-01-01

    Immunoaffinity-purified interleukin 2 (IL2) stimulated proliferation of large but not small B cells. Stimulation was observed even when B cells were cultured at very low cell densities (3 X 10(4) per microwell containing 0.2 ml of medium). Addition of small numbers of purified splenic T cells did not enhance the IL2-induced B-cell proliferative response. These results suggest that IL2 was not operating through contaminating T cells. B cells cultured with anti-Ig antibody in vitro showed enhan...

  1. Mixed Large Cell Neuroendocrine Carcinoma and Adenocarcinoma with Spindle Cell and Clear Cell Features in the Extrahepatic Bile Duct

    Directory of Open Access Journals (Sweden)

    John Wysocki

    2014-01-01

    Full Text Available Mixed adenoneuroendocrine carcinomas, spindle cell carcinomas, and clear cell carcinomas are all rare tumors in the biliary tract. We present the first case, to our knowledge, of an extrahepatic bile duct carcinoma composed of all three types. A 65-year-old man with prior cholecystectomy presented with painless jaundice, vomiting, and weight loss. CA19-9 and alpha-fetoprotein (AFP were elevated. Cholangioscopy revealed a friable mass extending from the middle of the common bile duct to the common hepatic duct. A bile duct excision was performed. Gross examination revealed a 3.6 cm intraluminal polypoid tumor. Microscopically, the tumor had foci of conventional adenocarcinoma (CK7-positive and CA19-9-postive surrounded by malignant-appearing spindle cells that were positive for cytokeratins and vimentin. Additionally, there were separate areas of large cell neuroendocrine carcinoma (LCNEC. Foci of clear cell carcinoma merged into both the LCNEC and the adenocarcinoma. Tumor invaded through the bile duct wall with extensive perineural and vascular invasion. Circumferential margins were positive. The patient’s poor performance status precluded adjuvant therapy and he died with recurrent and metastatic disease 5 months after surgery. This is consistent with the reported poor survival rates of biliary mixed adenoneuroendocrine carcinomas.

  2. Follicular dendritic cell sarcoma of the large intestine: A rare presentation

    OpenAIRE

    Samira Kumar Behera,; Sridhar Epari; Rajesh Kumar Bhola

    2014-01-01

    Follicular dendritic cell tumors are very rare neoplasms that often occur in lymph nodes. We report here a case in the colon, second in the series to be reported, in a 40 year male. The differentiation from gastrointestinal stromal tumor is emphasized. Tumor was involving the ascending colon without any obstructive feature. Microscopically, tumor cells are arranged in a pattern-less pattern, focal short fascicles. Tumor cells are large cells with varying shaped nuclei and ill d...

  3. Merkel Cell Polyomavirus Large T Antigen Has Growth-Promoting and Inhibitory Activities

    OpenAIRE

    Cheng, Jingwei; Rozenblatt-Rosen, Orit; Paulson, Kelly G.; Nghiem, Paul; DeCaprio, James A.

    2013-01-01

    Merkel cell carcinoma (MCC) is a rare and aggressive form of skin cancer. In at least 80% of all MCC, Merkel cell polyomavirus (MCPyV) DNA has undergone clonal integration into the host cell genome, and most tumors express the MCPyV large and small T antigens. In all cases of MCC reported to date, the integrated MCPyV genome has undergone mutations in the large T antigen. These mutations result in expression of a truncated large T antigen that retains the Rb binding or LXCXE motif but deletes...

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

    Science.gov (United States)

    2013-01-04

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

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

    Science.gov (United States)

    2016-06-20

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

  6. Recent Developments in β-Cell Differentiation of Pluripotent Stem Cells Induced by Small and Large Molecules

    Directory of Open Access Journals (Sweden)

    S. Suresh Kumar

    2014-12-01

    Full Text Available Human pluripotent stem cells, including human embryonic stem cells (hESCs and human induced pluripotent stem cells (hiPSCs, hold promise as novel therapeutic tools for diabetes treatment because of their self-renewal capacity and ability to differentiate into beta (β-cells. Small and large molecules play important roles in each stage of β-cell differentiation from both hESCs and hiPSCs. The small and large molecules that are described in this review have significantly advanced efforts to cure diabetic disease. Lately, effective protocols have been implemented to induce hESCs and human mesenchymal stem cells (hMSCs to differentiate into functional β-cells. Several small molecules, proteins, and growth factors promote pancreatic differentiation from hESCs and hMSCs. These small molecules (e.g., cyclopamine, wortmannin, retinoic acid, and sodium butyrate and large molecules (e.g. activin A, betacellulin, bone morphogentic protein (BMP4, epidermal growth factor (EGF, fibroblast growth factor (FGF, keratinocyte growth factor (KGF, hepatocyte growth factor (HGF, noggin, transforming growth factor (TGF-α, and WNT3A are thought to contribute from the initial stages of definitive endoderm formation to the final stages of maturation of functional endocrine cells. We discuss the importance of such small and large molecules in uniquely optimized protocols of β-cell differentiation from stem cells. A global understanding of various small and large molecules and their functions will help to establish an efficient protocol for β-cell differentiation.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. 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

  9. 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...

  10. Synthesis on power electronics for large fuel cells: From power conditioning to potentiodynamic analysis technique

    International Nuclear Information System (INIS)

    Highlights: • Active load for fuel cell managing electrical drive constraints: frequency and current ripple can be adjusted independently. • Multi-port resonant soft-switched topology for power management of a thirty kilowatt segmented PEM fuel cell. • Splitting current control strategy for power segmented PEM fuel cell in case of a segment is under fault. • Reversible Buck topology for large fuel cell with control of the fuel cell potential linked to current density nonlinearity. - Abstract: The work addressed in this paper deals with a synthesis on power electronic converters used for fuel cells. The knowledge gap concerns conceptually different electronic converter architectures for PEM (Proton Exchange Membrane) fuel cells able to perform three types of functionalities: The first one is the capacity of emulating an active load representative of electrical drive constraints. In that case, frequency and fuel cell current ripple can be set independently to investigate the dynamic behavior of the fuel cell. The second one is power conditioning applied to large high power and segmented fuel cell systems (“Large” represents several tens of cells and multi-kilowatt stacks), which is a non trivial consideration regarding the topological choices to be made for improving efficiency, compactness and ensure operation under faulty condition. A multi-port resonant isolated boost topology is analyzed enabling soft switching over a large operating range for a thirty kilowatt segmented fuel cell. A splitting current control strategy in case of a segment is under fault is proposed. Each considered converter topologies meet specific constraints regarding fuel cell stack design and power level. The third functionality is the ability for the power electronics to perform analysis and diagnosis techniques, like the cyclic voltammetry on large PEM fuel cell assemblies. The latter technique is an uncommon process for large fuel cell stacks since it is rather performed on

  11. My treatment approach to patients with diffuse large B-cell lymphoma.

    Science.gov (United States)

    Armitage, James O

    2012-02-01

    My favored treatment approach for patients with diffuse large B-cell lymphoma continues to evolve. Diffuse large B-cell lymphoma can now be cured in more than 50% of patients. This is a result of improved definitions of the disease, improved diagnostic capabilities, better staging and restaging techniques, a useful prognostic index to guide therapeutic decisions, and the development of increasingly effective therapies. Positron emission tomographic scans have improved the accuracy of both staging and restaging. Findings on a positron emission tomographic scan at the end of therapy are the best predictors of a good treatment outcome. Numerous subtypes of diffuse large B-cell lymphoma have been identified that require specific treatment approaches. For example, plasmablastic lymphoma typically lacks CD20 and does not benefit from treatment with rituximab. Diffuse large B-cell lymphoma originating in specific extranodal sites such as the central nervous system, testes, and skin presents special problems and requires specific treatment approaches. A subgroup of diffuse large B-cell lymphoma with a very high proliferative rate seems to have a poor outcome when treated with CHOP-R and does better with regimens used for patients with Burkitt lymphoma. New insights into the biology of these disorders are likely to further change treatment approaches. Recognition that diffuse large B-cell lymphoma is not one disease, but a variety of clinicopathologic syndromes provides the opportunity to further improve our ability to benefit patients. PMID:22305028

  12. 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

  13. Ocular Adnexal Diffuse Large B-cell LymphomaA Multicenter International Study

    DEFF Research Database (Denmark)

    Munch-Petersen, Helga D; Rasmussen, Peter K; Coupland, Sarah E;

    2015-01-01

    IMPORTANCE: The clinical features of diffuse large B-cell lymphoma (DLBCL) subtype of ocular adnexal lymphoma have not previously been evaluated in a large cohort to our knowledge. OBJECTIVE: To investigate the clinical features of ocular adnexal DLBCL (OA-DLBCL). DESIGN, SETTING, AND PARTICIPANT...

  14. Pulmonary Embolism as the Initial Manifestation of Large Cell Lung Cancer

    OpenAIRE

    Kim, Jin Kook; Lee, Sang Moo; Kim, Hyeon Tae; Uh, Sootaek; Chung, Yeontae; Kim, Yong Hoon; Park, Choonsik; Jin, So Young; Lee, Dong Hwa

    1992-01-01

    Lung cancer is known as a risk factor of pulmonary embolism. We experienced a case of pulmonary embolism combined with pleural effusion and pleuritic chest pain as the initial manifestation of large cell lung cancer, which is a relatively rare cell type of lung cancer in Korea. We report it with a review of the literature.

  15. 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.

  16. 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

  17. Large Grained Perovskite Solar Cells Derived from Single-Crystal Perovskite Powders with Enhanced Ambient Stability.

    Science.gov (United States)

    Yen, Hung-Ju; Liang, Po-Wei; Chueh, Chu-Chen; Yang, Zhibin; Jen, Alex K-Y; Wang, Hsing-Lin

    2016-06-15

    In this study, we demonstrate the large grained perovskite solar cells prepared from precursor solution comprising single-crystal perovskite powders for the first time. The resultant large grained perovskite thin film possesses a negligible physical (structural) gap between each large grain and is highly crystalline as evidenced by its fan-shaped birefringence observed under polarized light, which is very different from the thin film prepared from the typical precursor route (MAI + PbI2). PMID:27224963

  18. Large scale tracking of stem cells using sparse coding and coupled graphs

    DEFF Research Database (Denmark)

    Vestergaard, Jacob Schack; Dahl, Anders Lindbjerg; Holm, Peter;

    Stem cell tracking is an inherently large scale problem. The challenge is to identify and track hundreds or thousands of cells over a time period of several weeks. This requires robust methods that can leverage the knowledge of specialists on the field. The tracking pipeline presented here consists...... of a dictionary learning method for segmentation of phase contrast microscopy images. Linking of the cells between two images is solved by a graph formulation of the tracking problem....

  19. Breast schwannoma in a patient with diffuse large B-cell lymphoma: a case report

    Directory of Open Access Journals (Sweden)

    Salihoglu Ayse

    2012-12-01

    Full Text Available Abstract Introduction Schwannomas are mostly benign tumors arising from Schwann cells of the nerve sheaths. Breast schwannomas are very rare and account for only 2.6% of cases. As far as we know this is the first reported case of breast schwannoma discovered in a patient with diffuse large B-cell lymphoma. The breast schwannoma was evaluated with positron emission tomography and it exhibited moderate 18F-fluorodeoxyglucose uptake. Case presentation We present the case of a breast schwannoma in a 63-year-old Caucasian woman who was diagnosed with diffuse large B-cell lymphoma. Conclusion Imaging modalities including positron emission tomography-computed tomography failed to distinguish breast schwannoma from diffuse large B-cell lymphoma involvement of the breast.

  20. 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

  1. Merkel cell polyomavirus large T antigen has growth-promoting and inhibitory activities.

    Science.gov (United States)

    Cheng, Jingwei; Rozenblatt-Rosen, Orit; Paulson, Kelly G; Nghiem, Paul; DeCaprio, James A

    2013-06-01

    Merkel cell carcinoma (MCC) is a rare and aggressive form of skin cancer. In at least 80% of all MCC, Merkel cell polyomavirus (MCPyV) DNA has undergone clonal integration into the host cell genome, and most tumors express the MCPyV large and small T antigens. In all cases of MCC reported to date, the integrated MCPyV genome has undergone mutations in the large T antigen. These mutations result in expression of a truncated large T antigen that retains the Rb binding or LXCXE motif but deletes the DNA binding and helicase domains. However, the transforming functions of full-length and truncated MCPyV large T antigen are unknown. We compared the transforming activities of full-length, truncated, and alternatively spliced 57kT forms of MCPyV large T antigen. MCPyV large T antigen could bind to Rb but was unable to bind to p53. Furthermore, MCPyV-truncated large T antigen was more effective than full-length and 57kT large T antigen in promoting the growth of human and mouse fibroblasts. In contrast, expression of the MCPyV large T antigen C-terminal 100 residues could inhibit the growth of several different cell types. These data imply that the deletion of the C terminus of MCPyV large T antigen found in MCC serves not only to disrupt viral replication but also results in the loss of a distinct growth-inhibitory function intrinsic to this region. PMID:23514892

  2. T-Cell Lymphomas in South America and Europe

    Directory of Open Access Journals (Sweden)

    Monica Bellei

    2012-01-01

    Full Text Available Peripheral T-cell lymphomas are a group of rare neoplasms originating from clonal proliferation of mature post-thymic lymphocytes with different entities having specific biological characteristics and clinical features. As natural killer cells are closely related to T-cells, natural killer-cell lymphomas are also part of the group. The current World Health Organization classification recognizes four categories of T/natural killer-cell lymphomas with respect to their presentation: disseminated (leukemic, nodal, extranodal and cutaneous. Geographic variations in the distribution of these diseases are well documented: nodal subtypes are more frequent in Europe and North America, while extranodal forms, including natural killer-cell lymphomas, occur almost exclusively in Asia and South America. On the whole, T-cell lymphomas are more common in Asia than in western countries, usually affect adults, with a higher tendency in men, and, excluding a few subtypes, usually have an aggressive course and poor prognosis. Apart from anaplastic lymphoma kinase-positive anaplastic large cell lymphoma, that have a good outcome, other nodal and extranodal forms have a 5-year overall survival of about 30%. According to the principal prognostic indexes, the majority of patients are allocated to the unfavorable subset. In the past, the rarity of these diseases prevented progress in the understanding of their biology and improvements in the efficaciousness of therapy. Recently, international projects devoted to these diseases created networks promoting investigations on T-cell lymphomas. These projects are the basis of forthcoming cooperative, large scale trials to detail biologic characteristics of each sub-entity and to possibly individuate targets for new therapies.

  3. T-cell lymphomas in South america and europe.

    Science.gov (United States)

    Bellei, Monica; Chiattone, Carlos Sergio; Luminari, Stefano; Pesce, Emanuela Anna; Cabrera, Maria Elena; de Souza, Carmino Antonio; Gabús, Raul; Zoppegno, Lucia; Zoppegno, Lucia; Milone, Jorge; Pavlovsky, Astrid; Connors, Joseph Michael; Foss, Francine Mary; Horwitz, Steven Michael; Liang, Raymond; Montoto, Silvia; Pileri, Stefano Aldo; Polliack, Aaron; Vose, Julie Marie; Zinzani, Pier Luigi; Zucca, Emanuele; Federico, Massimo

    2012-01-01

    Peripheral T-cell lymphomas are a group of rare neoplasms originating from clonal proliferation of mature post-thymic lymphocytes with different entities having specific biological characteristics and clinical features. As natural killer cells are closely related to T-cells, natural killer-cell lymphomas are also part of the group. The current World Health Organization classification recognizes four categories of T/natural killer-cell lymphomas with respect to their presentation: disseminated (leukemic), nodal, extranodal and cutaneous. Geographic variations in the distribution of these diseases are well documented: nodal subtypes are more frequent in Europe and North America, while extranodal forms, including natural killer-cell lymphomas, occur almost exclusively in Asia and South America. On the whole, T-cell lymphomas are more common in Asia than in western countries, usually affect adults, with a higher tendency in men, and, excluding a few subtypes, usually have an aggressive course and poor prognosis. Apart from anaplastic lymphoma kinase-positive anaplastic large cell lymphoma, that have a good outcome, other nodal and extranodal forms have a 5-year overall survival of about 30%. According to the principal prognostic indexes, the majority of patients are allocated to the unfavorable subset. In the past, the rarity of these diseases prevented progress in the understanding of their biology and improvements in the efficaciousness of therapy. Recently, international projects devoted to these diseases created networks promoting investigations on T-cell lymphomas. These projects are the basis of forthcoming cooperative, large scale trials to detail biologic characteristics of each sub-entity and to possibly individuate targets for new therapies. PMID:23049383

  4. Modeling of organic photovoltaic cells with large fill factor and high efficiency

    Science.gov (United States)

    Yoo, Seunghyup; Domercq, Benoit; Marder, Seth R.; Armstrong, Neal R.; Kippelen, Bernard

    2004-11-01

    Organic photovoltaic cells exhibiting an ideal diode behavior with large fill factor (FF) are presented. It is demonstrated that the current-voltage characteristics can be well described using the equivalent circuit model that is also used for inorganic solar cells. Resistances associated with the cells and other diode parameters are extracted by fitting the experimental electrical characteristics using the equivalent circuit model. The effects of these parameters on FF are quantitatively described. Changes in these parameters under different illumination conditions are presented and compared to those occurring in inorganic pn-junction solar cells.

  5. Radiolabeled Monoclonal Antibody and Combination Chemotherapy Before Stem Cell Transplant in Treating Patients With High-Risk Lymphoid Malignancies

    Science.gov (United States)

    2016-06-13

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; B-cell Adult Acute Lymphoblastic Leukemia; B-cell Chronic Lymphocytic Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

  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. Monoclonal Antibody Therapy Before Stem Cell Transplant in Treating Patients With Relapsed or Refractory Lymphoid Malignancies

    Science.gov (United States)

    2015-12-07

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

  8. 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

  9. De novo CD5+ diffuse large B-cell lymphoma: Adverse outcomes with and without stem cell transplantation in a large, multicenter, rituximab treated cohort.

    Science.gov (United States)

    Alinari, Lapo; Gru, Alejandro; Quinion, Carl; Huang, Ying; Lozanski, Arletta; Lozanski, Gerard; Poston, Jacqueline; Venkataraman, Girish; Oak, Eunhye; Kreisel, Friederike; Park, Steven I; Matthews, Stephanie; Abramson, Jeremy S; Iris Lim, Hana; Martin, Peter; Cohen, Jonathon B; Evens, Andrew; Al-Mansour, Zeina; Singavi, Arun; Fenske, Timothy S; Blum, Kristie A

    2016-06-01

    De novo CD5+ diffuse large B-cell lymphomas (DLBCL) are a distinct subgroup of DLBCL with poor prognosis. However the role of rituximab-containing therapy and salvage stem cell transplantation in this patients' population remain to be defined. We retrospectively reviewed clinical features and outcomes of 102 patients with de novo CD5+ DLBCL treated with rituximab-containing therapy at nine different institutions. By Hans' criteria, 64 patients had activated B-cell (ABC) subtype, 24 germinal center B-cell (GCB) subtype, and 14 were not evaluated. No patients had a myc translocation. Eighty-three patients were treated with rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP), 7 with rituximab, etoposide, cyclophosphamide, doxorubicin, vincristine, prednisone (R-EPOCH), and 6 with R-CHOP with methotrexate, 3 g/m(2) . The overall response rate to front-line therapy was 85%. The 3-year progression free survival (PFS) and overall survival (OS) for all patients were 40 and 65%, respectively. The 3-year PFS for ABC- and GCB-subtypes was 34 and 45%, respectively. The 3-year OS for ABC- and GCB-subtypes was 62 and 67%, respectively. The median time to second treatment failure was 3 months and 1 month for ABC- and GCB-subtypes, respectively. Twenty of 28 (71%) transplanted patients with autologous, allogeneic, or both, relapsed. This study confirms the poor prognosis of de novo CD5+ DLBCL in a large multi-center cohort despite initial rituximab-containing chemotherapy and suggests that stem cell transplantation fails to salvage the majority of these patients. Approaches to prevent recurrence and/or novel therapies for relapsed disease are needed for this subgroup of DLBCL patients. Am. J. Hematol. 91:395-399, 2016. © 2016 Wiley Periodicals, Inc. PMID:26800311

  10. Development of Large-Format Lithium-Ion Cells with Silicon Anode and Low Flammable Electrolyte

    Science.gov (United States)

    Wu, James J.; Hernandez-Lugo, D. M.; Smart, M. C.; Ratnakumar, B. V.; Miller, T. B.; Lvovich, V. F.; Lytle, J. K.

    2014-01-01

    NASA is developing safe, high energy and high capacity lithium-ion cell designs and batteries for future missions under NASAs Advanced Space Power System (ASPS) project. Advanced cell components, such as high specific capacity silicon anodes and low-flammable electrolytes have been developed for improving the cell specific energy and enhancing safety. To advance the technology readiness level, we have developed large-format flight-type hermetically sealed battery cells by incorporating high capacity silicon anodes, commercially available lithium nickel, cobalt, aluminum oxide (NCA) cathodes, and low-flammable electrolytes. In this report, we will present the performance results of these various battery cells. In addition, we will also discuss the post-test cell analysis results as well.

  11. Primary diffuse large B-cell lymphoma of the ascending colon

    Directory of Open Access Journals (Sweden)

    Alan D. Gilman

    2013-04-01

    Full Text Available Primary colorectal lymphoma is a rare malignancy accounting for 3% of all gastrointestinal lymphomas and 0.1-0.5% of all colorectal malignancies. Among primary colorectal lymphomas, the most common histological subtype of colorectal lymphoma is diffuse large B-cell lymphoma. We report a case of an 84-year old Caucasian female who was admitted to the hospital because of a 2 days history of altered mental status. In the emergency department the patient was found to have acute kidney injury and hypercalcemia. On physical examination a large lower quadrant abdominal mass was palpated. Computed tomography scan of abdomen confirmed the presence of a mass along the cecum and proximal ascending colon. Colonoscopy showed a large ulcerated mass and biopsy was consistent with diffuse large B-cell lymphoma. The patient underwent colectomy but refused to receive chemotherapy.

  12. Prototype tests of a ''jet cell'' drift chamber for large-area muon detection

    International Nuclear Information System (INIS)

    Large-area, high-precision drift chambers, based on the ''jet cell'' concept, have been developed for the muon spectrometer of the ATLAS experiment at LHC. Emphasis is placed on the control and reduction of systematic error in the drift measurement and in the mechanical construction. Results of measurements on prototypes are given. These indicate that a global precision of σ< or∼70 μm is achievable for large-area chambers. (orig.)

  13. Prototype tests of a ``jet cell`` drift chamber for large-area muon detection

    Energy Technology Data Exchange (ETDEWEB)

    Bagnaia, P. [University ``La Sapienza`` and INFN, Rome (Italy); Barberio, E. [Phys. Dep. Calabria University and INFN, Cosenza (Italy); Beker, H. [University ``La Sapienza`` and INFN, Rome (Italy); Bilokon, H. [Laboratori Nationali di Frascati dell`INFN, Frascati (Italy); Bonini, R. [Laboratori Nationali di Frascati dell`INFN, Frascati (Italy); Borisov, A. [Institut Fiziki Vysokikh Ehnergij, Protvino (Russian Federation); Bussmann, K. [CERN, Geneva (Switzerland); Capradossi, G. [University ``La Sapienza`` and INFN, Rome (Italy); Chevalley, J.L. [CERN, Geneva (Switzerland); Chiarella, V. [Laboratori Nationali di Frascati dell`INFN, Frascati (Italy); Ciapetti, G. [University ``La Sapienza`` and INFN, Rome (Italy); Curatolo, M. [Laboratori Nationali di Frascati dell`INFN, Frascati (Italy); Di Tore, G. [CERN, Geneva (Switzerland); Dris, M. [National Technical Univ., Athens (Greece); Esposito, B. [Laboratori Nationali di Frascati dell`INFN, Frascati (Italy); Fabjan, C.W. [CERN, Geneva (Switzerland); Filippas, T. [National Technical Univ., Athens (Greece); Franz, A. [CERN, Geneva (Switzerland); Gaumann, E. [CERN, Geneva (Switzerland); Gayde, J.C. [CERN, Geneva (Switzerland); Gazis, E.N. [National Technical Univ., Athens (Greece); Goret, B. [CERN, Geneva (Switzerland); Goryatchev, V. [Institut Fiziki Vysokikh Ehnergij, Protvino (Russian Federation); Klempt, W. [CERN, Geneva (Switzerland); Kobayashi, T. [University of Tokyo, Tokyo (Japan); Komamiya, S. [University of Tokyo, Tokyo (Japan); Kozhin, A. [Institut Fiziki Vysokikh Ehnergij, Protvino (Russian Federation); Lasseur, C. [CERN, Geneva (Switzerland); Liguori, D. [Phys. Dep. Calabria University and INFN, Cosenza (Italy); Mashimo, T. [University of Tokyo, Tokyo (Japan); Nisati, A. [University ``La Sapienza`` and INFN, Rome (Italy); Passamonti, L. [Laboratori Nationali di Frascati dell`INFN, Frascati (Italy); Perciballi, M. [University ``La Sapienza`` and INFN, Rome (Italy)

    1996-01-21

    Large-area, high-precision drift chambers, based on the ``jet cell`` concept, have been developed for the muon spectrometer of the ATLAS experiment at LHC. Emphasis is placed on the control and reduction of systematic error in the drift measurement and in the mechanical construction. Results of measurements on prototypes are given. These indicate that a global precision of {sigma}large-area chambers. (orig.).

  14. Stem Cell Expansion and Differentiation in Microcarrier-Based Bioreactors for Large Scale Production

    OpenAIRE

    Sart, Sébastien; Agathos, Spiros N.; Li, Yan; Annual meeting of the American Institute of Chemical Engineers (AIChE)

    2013-01-01

    Microcarriers have been widely used for various biotechnology applications because of their high scale-up potential, high reproducibility on regulating cellular behaviors, and their compliance with current Good Manufacturing Practices (cGMP). Recently, microcarriers have been investigated for stem cell expansion and differentiation, enabling potential scale-up of stem cell-derived products in large bioreactors. This presentation summarizes recent advances of using microcarriers for mesenchyma...

  15. Clinical-scale expansion of mesenchymal stromal cells: a large banking experience

    OpenAIRE

    Lechanteur, Chantal; Briquet, Alexandra; Giet, Olivier; Delloye, Olivier; Baudoux, Etienne; Beguin, Yves

    2016-01-01

    Background Mesenchymal stromal cells (MSC) are largely investigated in clinical trials aiming to control inappropriate immune reactions (GVHD, Crohn’s disease, solid organ transplantation). As the percentage of MSC precursors in bone marrow is very low, these must be expanded in vitro to obtain therapeutic cell doses. We describe here the constitution of an allogeneic human third-party MSC bank from screened healthy volunteer donors in compliance with quality specifications and ISCT-release c...

  16. Large animal induced pluripotent stem cells as pre-clinical models for studying human disease

    OpenAIRE

    Jordan R Plews; Gu, Mingxia; Longaker, Michael T.; Joseph C. Wu

    2012-01-01

    Abstract The derivation of human embryonic stem cells and subsequently human induced pluripotent stem cells (iPSCs) has energized regenerative medicine research and enabled seemingly limitless applications. Although small animal models, such as mouse models, have played an important role in the progression of the field, typically, they are poor representations of the human disease phenotype. As an alternative, large animal models should be explored as a potentially better approach for clinica...

  17. Large cell neuroendocrine carcinoma (LCNEC) of the urinary bladder: a case report

    OpenAIRE

    Colarossi Cristina; Pino Piero; Giuffrida Dario; Aiello Eleonora; Costanzo Rosario; Martinetti Daniela; Memeo Lorenzo

    2013-01-01

    Abstract Neuroendocrine carcinoma of the urinary bladder is a rare entity, accounting less then 1% of urinary bladder malignancies. The vast majority of the neuroendocrine carcinoma of the urinary bladder is represented by small cell neuroendocrine carcinoma while just few cases of large cell neuroendocrine carcinoma (LCNEC) have been reported. In this cases report we describe a rare case of primary bladder LCNEC. Virtual Slides The virtual slide(s) for this article can be found here: http://...

  18. Identification of a region of simian virus 40 large T antigen required for cell transformation.

    OpenAIRE

    Chen, S.; Paucha, E

    1990-01-01

    A series of replication-competent simian virus 40 (SV40) large T antigens with point and deletion mutations in the amino acid sequence between residues 105 and 115 were examined for the ability to immortalize primary cultures of mouse and rat cells. The results show that certain mutants, including one that deletes the entire region, are able to immortalize. However, consistent with previous data, the immortalized cells are not fully transformed, as judged by doubling time, sensitivity to conc...

  19. PMA/IONO affects diffuse large B-cell lymphoma cell growth through upregulation of A20 expression.

    Science.gov (United States)

    Yang, Wenxiu; Li, Yi; Li, Pinhao; Wang, Lingling

    2016-08-01

    Diffuse large B-cell lymphoma (DLBCL) is a common non-Hodgkin lymphoma. A20 and mucosa-associated lymphoid tissue lymphoma translocation gene 1 (MALT1) are known to be related to DLBCL pathogenesis and progression. This study aimed to assess the effects of phorbol myristate acetate/ionomycin (PMA/IONO) on the growth and apoptosis of the DLBCL cell line OCI-LY1, and their associations with A20, MALT1 and survivin levels. Cell viability was assessed by MTT assay. Cell cycle distribution and apoptosis were evaluated using flow cytometry after incubation with Annexin V-FITC/propidium iodide (PI) and RNase/PI, respectively. Gene and protein expression levels were determined by quantitative real-time PCR and western blotting, respectively. To further determine the role of A20, this gene was silenced in the OCI-LY1 cell line by specific siRNA transfection. A20 protein levels were higher in the OCI-LY1 cells treated with PMA/IONO compared with the controls, and were positively correlated with the concentration and treatment time of IONO, but not with changes of PMA and MALT1. Meanwhile, survivin expression was reduced in the OCI-LY1 cells after PMA/IONO treatment. In addition, OCI-LY1 proliferation was markedly inhibited, with a negative correlation between cell viability and IONO concentration. In concordance, apoptosis rates were higher in the OCI-LY1 cells after PMA + IONO treatment. Cell cycle distribution differed between the OCI-LY1 cells with and without PMA/IONO treatment only at 24 h, with increased cells in the G0/G1 stage after PMA/IONO treatment. These findings indicate that PMA/IONO promotes the apoptosis and inhibits the growth of DLBCL cells, in association with A20 upregulation. Thus, A20 may be a potential therapeutic target for DLBCL. PMID:27349720

  20. Classification of large circulating tumor cells isolated with ultra-high throughput microfluidic Vortex technology.

    Science.gov (United States)

    Che, James; Yu, Victor; Dhar, Manjima; Renier, Corinne; Matsumoto, Melissa; Heirich, Kyra; Garon, Edward B; Goldman, Jonathan; Rao, Jianyu; Sledge, George W; Pegram, Mark D; Sheth, Shruti; Jeffrey, Stefanie S; Kulkarni, Rajan P; Sollier, Elodie; Di Carlo, Dino

    2016-03-15

    Circulating tumor cells (CTCs) are emerging as rare but clinically significant non-invasive cellular biomarkers for cancer patient prognosis, treatment selection, and treatment monitoring. Current CTC isolation approaches, such as immunoaffinity, filtration, or size-based techniques, are often limited by throughput, purity, large output volumes, or inability to obtain viable cells for downstream analysis. For all technologies, traditional immunofluorescent staining alone has been employed to distinguish and confirm the presence of isolated CTCs among contaminating blood cells, although cells isolated by size may express vastly different phenotypes. Consequently, CTC definitions have been non-trivial, researcher-dependent, and evolving. Here we describe a complete set of objective criteria, leveraging well-established cytomorphological features of malignancy, by which we identify large CTCs. We apply the criteria to CTCs enriched from stage IV lung and breast cancer patient blood samples using the High Throughput Vortex Chip (Vortex HT), an improved microfluidic technology for the label-free, size-based enrichment and concentration of rare cells. We achieve improved capture efficiency (up to 83%), high speed of processing (8 mL/min of 10x diluted blood, or 800 μL/min of whole blood), and high purity (avg. background of 28.8±23.6 white blood cells per mL of whole blood). We show markedly improved performance of CTC capture (84% positive test rate) in comparison to previous Vortex designs and the current FDA-approved gold standard CellSearch assay. The results demonstrate the ability to quickly collect viable and pure populations of abnormal large circulating cells unbiased by molecular characteristics, which helps uncover further heterogeneity in these cells. PMID:26863573

  1. Increased risk of gastric adenocarcinoma after treatment of primary gastric diffuse large B-cell lymphoma

    International Nuclear Information System (INIS)

    There have been sporadic reports about synchronous as well as metachronous gastric adenocarcinoma and primary gastric lymphoma. Many reports have dealt with metachronous gastric adenocarcinoma in mucosa-associated lymphoid tissue lymphoma of stomach. But to our knowledge, there have been no reports that document the increased incidence of metachronous gastric adenocarcinoma in patients with gastric diffuse large B-cell lymphoma. This retrospective study was conducted to estimate the incidence of metachronous gastric adenocarcinoma after primary gastric lymphoma treatment, especially in diffuse large B-cell lymphoma. The retrospective cohort study of 139 primary gastric lymphoma patients treated with radiotherapy at our hospital. Mean observation period was 61.5 months (range: 3.7-124.6 months). Patients profile, characteristics of primary gastric lymphoma and metachronous gastric adenocarcinoma were retrieved from medical records. The risk of metachronous gastric adenocarcinoma was compared with the risk of gastric adenocarcinoma in Japanese population. There were 10 (7.2%) metachronous gastric adenocarcinoma patients after treatment of primary gastric lymphomas. It was quite high risk compared with the risk of gastric carcinoma in Japanese population of 54.7/100,000. Seven patients of 10 were diffuse large B-cell lymphoma and other 3 patients were mixed type of diffuse large B-cell lymphoma and mucosa associated lymphoid tissue lymphoma. Four patients of 10 metachronous gastric adenocarcinomas were signet-ring cell carcinoma and two patients died of gastric adenocarcinoma. Metachronous gastric adenocarcinoma may have a more malignant potential than sporadic gastric adenocarcinoma. Old age, Helicobacter pylori infection and gastric mucosal change of chronic gastritis and intestinal metaplasia were possible risk factors for metachronous gastric adenocarcinoma. There was an increased risk of gastric adenocarcinoma after treatment of primary gastric lymphoma

  2. Microarray-based classification of diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Poulsen, Christian Bjørn; Borup, Rehannah; Nielsen, Finn Cilius;

    2005-01-01

    OBJECTIVE: Hierarchical clusterings of diffuse large B-cell lymphoma (DLBCL) based on gene expression signatures have previously been used to classify DLBCL into Germinal Center B-cell (GCB) and Activated B-cell (ABC) types. To examine if it was feasible to perform a cross-platform validation on...... of classifier genes was generated by analysis of 34 patients that were consistently classified as GCB or ABC in the above analyses. Seventy-eight genes were selected and demonstrated on two previously published data sets (Shipp et al. Nat Med 2002;8:68-74 and Houldsworth et al. Blood 2004...

  3. How T-cells use large deviations to recognize foreign antigens

    CERN Document Server

    Zint, Natali; Hollander, Frank den

    2008-01-01

    A stochastic model for the activation of T-cells is analysed. T-cells are part of the immune system and recognize foreign antigens against a background of the body's own molecules. The model under consideration is a slight generalization of a model introduced by Van den Berg, Rand and Burroughs in 2001, and is capable of explaining how this recognition works on the basis of rare stochastic events. With the help of a refined large deviation theorem and numerical evaluation it is shown that, for a wide range of parameters, T-cells can distinguish reliably between foreign antigens and self-antigens.

  4. 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, ...

  5. 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...

  6. Reduced-Intensity Conditioning Before Donor Stem Cell Transplant in Treating Patients With High-Risk Hematologic Malignancies

    Science.gov (United States)

    2016-04-11

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; de Novo Myelodysplastic Syndromes; Essential Thrombocythemia; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Juvenile Myelomonocytic Leukemia; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Polycythemia Vera; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non

  7. Diffuse Large B Cell Lymphoma in a Patient with Hypocomplementemic Urticarial Vasculitis

    Directory of Open Access Journals (Sweden)

    Calvo-Romero J

    2003-01-01

    Full Text Available Hypocomplementemic urticarial vasculitis (HUV is known to be associated with malignancies. Urticarial vasculitis has been linked to lymphomas, but to our knowledge, the association of HUV and non-Hodgkin lymphoma has not been described so far. A patient with HUV who developed 10 years later a diffuse large B cell lymphoma is reported here.

  8. Diffuse Large B Cell Lymphoma in a Patient with Hypocomplementemic Urticarial Vasculitis

    OpenAIRE

    Calvo-Romero J

    2003-01-01

    Hypocomplementemic urticarial vasculitis (HUV) is known to be associated with malignancies. Urticarial vasculitis has been linked to lymphomas, but to our knowledge, the association of HUV and non-Hodgkin lymphoma has not been described so far. A patient with HUV who developed 10 years later a diffuse large B cell lymphoma is reported here.

  9. Genetic Landscapes of Relapsed and Refractory Diffuse Large B-Cell Lymphomas

    DEFF Research Database (Denmark)

    Morin, Ryan D; Assouline, Sarit; Alcaide, Miguel; Mohajeri, Arezoo; Johnston, Rebecca L; Chong, Lauren; Grewal, Jasleen; Yu, Stephen; Fornika, Daniel; Bushell, Kevin; Nielsen, Torsten Holm; Petrogiannis-Haliotis, Tina; Crump, Michael; Tosikyan, Axel; Grande, Bruno M; MacDonald, David; Rousseau, Caroline; Bayat, Maryam; Sesques, Pierre; Froment, Remi; Albuquerque, Marco; Monczak, Yury; Oros, Kathleen Klein; Greenwood, Celia; Riazalhosseini, Yasser; Arseneault, Madeleine; Camlioglu, Errol; Constantin, André; Pan-Hammarstrom, Qiang; Peng, Roujun; Mann, Koren K; Johnson, Nathalie A

    2015-01-01

    PURPOSE: Relapsed or refractory diffuse large B-cell lymphoma (rrDLBCL) is fatal in 90% of patients, and yet little is known about its biology. EXPERIMENTAL DESIGN: Using exome sequencing, we characterized the mutation profiles of 38 rrDLBCL biopsies obtained at the time of progression after...

  10. Frequent disruption of the RB1 pathway in diffuse large B cell lymphoma

    DEFF Research Database (Denmark)

    Møller, M B; Kania, Per Walter; Ino, Y;

    2000-01-01

    In the present study, we analysed 34 de novo diffuse large B cell lymphoma (DLCL) from a population-based lymphoma registry for alterations of the RB1 pathway at the genetic (RB1 and CDK4) and protein (pRb, cyclin D1, cyclin D3, CDK4, and E2F-1) level. The results were correlated with the data fr...

  11. Reactivation of hepatitis D virus after chemotherapy for diffuse large B cell lymphoma despite lamivudine prophylaxis

    DEFF Research Database (Denmark)

    Andersen, Ellen Sloth; Gerstoft, Jan; Weis, Nina Margrethe

    2010-01-01

    We describe a case of reactivation of hepatitis D virus (HDV) in a patient treated with chemotherapy for a diffuse large B cell lymphoma despite lamivudine prophylaxis. This case suggests that previously cleared HDV should be considered when administering chemotherapy to patients with lymphoma....

  12. Efficacy of adjusted BACOD regimen on the treatment of relapsed refractory diffuse large B cell lymphoma

    Institute of Scientific and Technical Information of China (English)

    龚格格

    2014-01-01

    Objective To compare the efficacy and adverse events of adjusted BACOD(bleomycin,doxorubicin,cyclophosphamide,vincristine,dexamethasone)regimen(continuous intravenous infusion)and conventional BACOD regimen(conventional intravenous drip)in the treatment of relapsed and refractory diffuse large B cell lymphoma(DLBCL).Methods Retrospective analysis of63 cases of relapsed or refractory DLBCL patients was performed,32 patients received conventional BACOD

  13. Relationships among hepatitis C virus, hepatocellular carcinoma, and diffuse large B cell lymphoma: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Byun, Hyuk Jun; Kim, Seong Hoon [Dept. of Radiology, Daegu Fatima Hospital, Daegu (Korea, Republic of)

    2015-07-15

    Hepatitis C virus (HCV) is one of the main causes of hepatocellular carcinoma (HCC). Recent studies have reported various associations between HCV and the incidence of non-Hodgkin's lymphoma. We report the radiologic findings in a rare case of simultaneous occurrence of HCC and diffuse large B cell lymphoma in a HCV carrier.

  14. Development of large engineered cartilage constructs from a small population of cells.

    Science.gov (United States)

    Brenner, Jillian M; Kunz, Manuela; Tse, Man Yat; Winterborn, Andrew; Bardana, Davide D; Pang, Stephen C; Waldman, Stephen D

    2013-01-01

    Confronted with articular cartilage's limited capacity for self-repair, joint resurfacing techniques offer an attractive treatment for damaged or diseased tissue. Although tissue engineered cartilage constructs can be created, a substantial number of cells are required to generate sufficient quantities of tissue for the repair of large defects. As routine cell expansion methods tend to elicit negative effects on chondrocyte function, we have developed an approach to generate phenotypically stable, large-sized engineered constructs (≥3 cm(2) ) directly from a small amount of donor tissue or cells (as little as 20,000 cells to generate a 3 cm(2) tissue construct). Using rabbit donor tissue, the bioreactor-cultivated constructs were hyaline-like in appearance and possessed a biochemical composition similar to native articular cartilage. Longer bioreactor cultivation times resulted in increased matrix deposition and improved mechanical properties determined over a 4 week period. Additionally, as the anatomy of the joint will need to be taken in account to effectively resurface large affected areas, we have also explored the possibility of generating constructs matched to the shape and surface geometry of a defect site through the use of rapid-prototyped defect tissue culture molds. Similar hyaline-like tissue constructs were developed that also possessed a high degree of shape correlation to the original defect mold. Future studies will be aimed at determining the effectiveness of this approach to the repair of cartilage defects in an animal model and the creation of large-sized osteochondral constructs. PMID:23197468

  15. Progressive thrombosis after treatment of diffuse large cell non-Hodgkin's lymphoma and concomitant lupus anticoagulant.

    Science.gov (United States)

    Keung, Y K; Cobos, E; Meyerrose, G E; Roberson, G H

    1996-01-01

    We report a case of diffuse large cell non-Hodgkin's lymphoma with concomitant lupus anticoagulant at initial diagnosis. Progressive thrombosis occurred despite radiologically proven response of the lymphoma after chemotherapy treatment. Extraordinary bone scintigraphy with multiple "cold" lesions probably due to bone ischemia is described. PMID:8624478

  16. [Polychemotherapy of large cell carcinoma of the lung: a case of complete remission].

    Science.gov (United States)

    Spaghi, A; Costa, D; Gangarossa, I; Castoldi, O; Pasotti, D; Albergati, M G; Nastasi, G

    1989-01-01

    A case of a patient with large cell pulmonary carcinoma is presented. Being inoperable, the patient was treated at first with multiple drug chemotherapy and the result was the disappearance of the pulmonary lesions. The unusual favourable therapeutic response and the protocols of polychemotherapy used are discussed. PMID:2544780

  17. Cytomegalovirus enterocolitis in a patient with diffuse large B-cell lymphoma after chemotherapy with rituximab

    Institute of Scientific and Technical Information of China (English)

    Jason Seewoodhary

    2006-01-01

    Rituximab has been associated with the development of cytomegalovirus enterocolitis in immunosuppressed patients. A 51-year-old patient with diffuse large B-cell lymphoma who received a conditioning chemotherapy regimen (RCVP and RICE) consisting of rituximab before bone marrow transplantation went on to develop cytomegalovirus enterocolitis. This supports evidence from previously described cases that rituximab may be associated with cytomegalovirus enterocolitis.

  18. Large Cell Neuroendocrine Carcinoma of the Rectum Presenting with Extensive Metastatic Disease

    Directory of Open Access Journals (Sweden)

    Vinay Minocha

    2014-01-01

    Full Text Available Introduction. Rectal large cell neuroendocrine carcinoma (LCNEC is a poorly differentiated neoplasm that is very rare and belongs within the poorest prognostic subgroup among primary colorectal neoplasms. Here, we describe a case of LCNEC of the rectum, which highlights the aggressive clinical course and poor prognosis associated with this disease. Case Presentation. We report a case of a 63-year-old male who presented to our hospital with a one-month history of lower abdominal pain, constipation, and weight loss. A computed tomography (CT scan of the chest, abdomen, and pelvis revealed a rectal mass as well as metastatic disease of the liver and lung. Flexible sigmoidoscopy revealed a fungating, ulcerated and partially obstructing rectal mass located 6 cm from the anal verge. This mass was biopsied and pathological examination of the resected specimen revealed features consistent with a large cell neuroendocrine carcinoma. Conclusion. Rectal large cell neuroendocrine carcinomas are rare and have a significantly worse prognosis than adenocarcinomas. At diagnosis, a higher stage and metastatic disease are likely to be found. It is important to differentiate large cell, poorly differentiated neuroendocrine carcinomas from adenocarcinomas of the colon and rectum pathologically because patients may benefit from alternative cytotoxic chemotherapeutic regimens.

  19. Ab initio phenomenological simulation of the growth of large tumor cell populations

    CERN Document Server

    Chignola, R; Milotti, E; Pellegrina, C D; Chignola, Roberto; Fabbro, Alessio Del; Milotti, Edoardo; Pellegrina, Chiara Dalla

    2007-01-01

    In a previous paper we have introduced a phenomenological model of cell metabolism and of the cell cycle to simulate the behavior of large tumor cell populations (Chignola R and Milotti E, Phys. Biol. 2 (2005) 8-22). Here we describe a refined and extended version of the model that includes some of the complex interactions between cells and their surrounding environment. The present version takes into consideration several additional energy-consuming biochemical pathways such as protein and DNA synthesis, the tuning of extracellular pH and of the cell membrane potential. The control of the cell cycle - that was previously modeled by means of ad hoc thresholds - has been directly addressed here by considering checkpoints from proteins that act as targets for phosphorylation on multiple sites. As simulated cells grow, they can now modify the chemical composition of the surrounding environment which in turn acts as a feedback mechanism to tune cell metabolism and hence cell proliferation: in this way we obtain g...

  20. Large area, low cost space solar cells with optional wraparound contacts

    Science.gov (United States)

    Michaels, D.; Mendoza, N.; Williams, R.

    1981-01-01

    Design parameters for two large area, low cost solar cells are presented, and electron irradiation testing, thermal alpha testing, and cell processing are discussed. The devices are a 2 ohm-cm base resistivity silicon cell with an evaporated aluminum reflector produced in a dielectric wraparound cell, and a 10 ohm-cm silicon cell with the BSF/BSR combination and a conventional contact system. Both cells are 5.9 x 5.9 cm and require 200 micron thick silicon material due to mission weight constraints. Normalized values for open circuit voltage, short circuit current, and maximum power calculations derived from electron radiation testing are given. In addition, thermal alpha testing values of absorptivity and emittance are included. A pilot cell processing run produced cells averaging 14.4% efficiencies at AMO 28 C. Manufacturing for such cells will be on a mechanized process line, and the area of coverslide application technology must be considered in order to achieve cost effective production.

  1. Secondary pancreatic involvement by a diffuse large B-cell lymphoma presenting as acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    M Wasif Saif; Sapna Khubchandani; Marek Walczak

    2007-01-01

    Diffuse large B-cell lymphoma is the most common type of non-Hodgkin's lymphoma. More than 50% of patients have some site of extra-nodal involvement at diagnosis,including the gastrointestinal tract and bone marrow.However, a diffuse large B-cell lymphoma presenting as acute pancreatitis is rare. A 57-year-old female presented with abdominal pain and matted lymph nodes in her axilla. She was admitted with a diagnosis of acute pancreatitis. Abdominal computed tomography (CT) scan showed diffusely enlarged pancreas due to infiltrative neoplasm and peripancreatic lymphadenopathy. Biopsy of the axillary mass revealed a large B-cell lymphoma.The patient was classified as stage Ⅳ, based on the Ann Arbor Classification, and as having a high-risk lymphoma,based on the International Prognostic Index. She was started on chemotherapy with CHOP (cyclophosphamide,doxorubicin, vincristine and prednisone). Within a week after chemotherapy, the patient's abdominal pain resolved. Follow-up CT scan of the abdomen revealed a marked decrease in the size of the pancreas and peripancreatic lymphadenopathy. A literature search revealed only seven cases of primary involvement of the pancreas in B-cell lymphoma presenting as acute pancreatitis. However, only one case of secondary pancreatic involvement by B-cell lymphoma presenting as acute pancreatitis has been published. Our case appears to be the second report of such a manifestation.Both cases responded well to chemotherapy.

  2. SV40 large T antigen-specific human T cell memory responses.

    Science.gov (United States)

    Coleman, Sharon; Gibbs, Allen; Butchart, Eric; Mason, Malcolm D; Jasani, Bharat; Tabi, Zsuzsanna

    2008-08-01

    The continued presence of simian virus 40 (SV40), a monkey polyomavirus, in man is confirmed by the regular detection of SV40-specific antibodies in 5-10% of children who are unlikely to have received contaminated polio-vaccines. The aim of our experiments was to find cellular immunological evidence of SV40 infection in humans by testing memory T cell responses to SV40 large T antigen (Tag). As there is some indication that the virus may be present in malignant pleural mesothelioma (MPM) cells, we analyzed T cell responses in MPM patients and in healthy donors. The frequencies of responding T cells to overlapping Tag peptides were tested by cytokine flow cytometry. CD8+ T cells from 4 of 32 MPM patients responded (above twofold of control) to SV40 Tag peptides, while no positive responses were detected in 12 healthy donors. Within SV40 Tag we identified three 15 amino acid-long immunogenic sequences and one 9 amino acid-long T cell epitope (p138) (138FPSELLSFL146), the latter including a HLA-B7-restriction motif. T cell responses to p138 were SV40-specific as T cells stimulated with p138 did not cross-react with the corresponding sequences of Tag of human polyomaviruses BKV and JCV. Similarly, the relevant BKV and JCV Tag peptides did not generate T cell responses against SV40 TAg p138. Peptide-stimulated T cells also killed SV40 Tag-transfected target cells. This article demonstrates the presence, and provides a detailed analysis, of SV40-specific T cell memory in man. PMID:18551603

  3. Comparison of two methods for short circuit current measurement of large size solar cell

    Science.gov (United States)

    Huang, Xuebo; Quan, Chenggen; Kng, Jerald

    2015-07-01

    The differential spectral responsivity (DSR) measurement and the solar simulator based current to voltage characterisation methods are two accurate methods for measuring the short circuit current, a critical parameter, of a solar cell under standard testing conditions. For the calibration of World Photovoltaic Scale (WPVS) reference solar cell with small size (20 mm x 20 mm), the measurement results using these two methods are agreed well within 1%. But for the calibration of large size (e.g. 156 mm x 156 mm) of solar cell, the measurement results using two methods are not agreed well and their deviation could be more than 10 %. In DSR method, the short circuit current of a solar cell is determined through measuring its relative irradiance spectral responsivity in spectral range from 280 nm to 1200 nm and its absolute irradiance responsivity at wavelength of 650 nm by reference standard photodiodes. As the detective area of large size solar cell (detective area: 156 mm x 156 mm) is much bigger than that of standard photodiodes (detective area: 12.56 mm2), the spatial uniformity of irradiance of modulated monochromatic probe beam on the test solar cell and the standard photodiode is critical for calculation of absolute irradiance responsivity of the test solar cell. The correction for the calculation must be done according to the measured spatial uniformity of probe beam and the detective areas of the test solar cell and standard photodiodes. The experiment showed the correction factor and its uncertainty are smaller if the detective areas difference between the test solar cell and the standard is smaller. Based on this observation, a standard solar cell (detective area: 20 mm x 20 mm) instead of standard photodiodes was used to calibrate absolute irradiance responsivity of the test solar cell (detective area: 156 mm x 156 mm) at wavelength of 650 nm. After such improvement, measurement results using two different methods agree well about 3 % for the large size

  4. Cell density related gene expression: SV40 large T antigen levels in immortalized astrocyte lines

    Directory of Open Access Journals (Sweden)

    Jacobberger James W

    2002-04-01

    Full Text Available Abstract Background Gene expression is affected by population density. Cell density is a potent negative regulator of cell cycle time during exponential growth. Here, we asked whether SV40 large T antigen (Tag levels, driven by two different promoters, changed in a predictable and regular manner during exponential growth in clonal astrocyte cell lines, immortalized and dependent on Tag. Results Expression and cell cycle phase fractions were measured and correlated using flow cytometry. T antigen levels did not change or increased during exponential growth as a function of the G1 fraction and increasing cell density when Tag was transcribed from the Moloney Murine Leukemia virus (MoMuLV long terminal repeat (LTR. When an Rb-binding mutant T antigen transcribed from the LTR was tested, levels decreased. When transcribed from the herpes thymidine kinase promoter, Tag levels decreased. The directions of change and the rates of change in Tag expression were unrelated to the average T antigen levels (i.e., the expression potential. Conclusions These data show that Tag expression potential in these lines varies depending on the vector and clonal variation, but that the observed level depends on cell density and cell cycle transit time. The hypothetical terms, expression at zero cell density and expression at minimum G1 phase fraction, were introduced to simplify measures of expression potential.

  5. Fludarabine Phosphate and Total-Body Radiation Followed by Donor Peripheral Blood Stem Cell Transplant and Immunosuppression in Treating Patients With Hematologic Malignancies

    Science.gov (United States)

    2015-12-01

    Acute Myeloid Leukemia/Transient Myeloproliferative Disorder; Acute Undifferentiated Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Blastic Plasmacytoid Dendritic Cell Neoplasm; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Burkitt Lymphoma; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Myelomonocytic Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Juvenile Myelomonocytic Leukemia; Mast Cell Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Primary Systemic Amyloidosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell

  6. Thermal Behaviour Investigation of a Large and High Power Lithium Iron Phosphate Cylindrical Cell

    Directory of Open Access Journals (Sweden)

    Odile Capron

    2015-09-01

    Full Text Available This paper investigates the thermal behaviour of a large lithium iron phosphate (LFP battery cell based on its electrochemical-thermal modelling for the predictions of its temperature evolution and distribution during both charge and discharge processes. The electrochemical-thermal modelling of the cell is performed for two cell geometry approaches: homogeneous (the internal region is considered as a single region and discrete (the internal region is split into smaller regions for each layer inside the cell. The experimental measurements and the predictions of the cell surface temperature achieved with the simulations for both approaches are in good agreement with 1.5 °C maximum root mean square error. From the results, the maximum cell surface temperature and temperature gradient between the internal and the surface regions are around 31.3 °C and 1.6 °C. The temperature gradient in the radial direction is observed to be greater about 1.1 °C compared to the longitudinal direction, which is caused by the lower thermal conductivity of the cell in the radial compared to the longitudinal direction. During its discharge, the reversible, the ohmic and the reaction heat generations inside the cell reach up to 2 W, 7 W and 17 W respectively. From the comparison of the two modelling approaches, this paper establishes that the homogeneous modelling of the cell internal region is suitable for the study of a single cylindrical cell and is appropriate for the two-dimensional thermal behaviour investigation of a battery module made of multiple cells.

  7. Graphene-based large area dye-sensitized solar cell modules

    Science.gov (United States)

    Casaluci, Simone; Gemmi, Mauro; Pellegrini, Vittorio; di Carlo, Aldo; Bonaccorso, Francesco

    2016-02-01

    We demonstrate spray coating of graphene ink as a viable method for large-area fabrication of graphene-based dye-sensitized solar cell (DSSC) modules. A graphene-based ink produced by liquid phase exfoliation of graphite is spray coated onto a transparent conductive oxide substrate to realize a large area (>90 cm2) semi-transparent (transmittance 44%) counter-electrode (CE) replacing platinum, the standard CE material. The graphene-based CE is successfully integrated in a large-area (43.2 cm2 active area) DSSC module achieving a power conversion efficiency of 3.5%. The approach demonstrated here paves the way to all-printed, flexible, and transparent graphene-based large-area and cost-effective photovoltaic devices on arbitrary substrates.

  8. Clinical Implications of Phosphorylated STAT3 Expression in de novo Diffuse Large B-cell Lymphoma

    DEFF Research Database (Denmark)

    Ok, Chi Y; Chen, Jiayu; Xu-Monette, Ziju;

    2014-01-01

    phosphorylated STAT3 (pSTAT3) on prognosis are limited. EXPERIMENTAL DESIGN: We evaluated expression of pSTAT3 in de novo DLBCL using immunohistochemistry, gene expression profiling (GEP), and gene set enrichment analysis (GSEA). Results were analyzed in correlation with cell-of-origin (COO), critical lymphoma......PURPOSE: Activated signal transducer and activator of transcription 3 (STAT3) regulates tumor growth, invasion, cell proliferation, angiogenesis, immune response, and survival. Data regarding expression of phosphorylated (activated) STAT3 in diffuse large B-cell lymphoma (DLBCL) and the impact of...... biomarkers, and genetic translocations. RESULTS: pSTAT3 expression was observed in 16% of DLBCL and was associated with advanced stage, multiple extranodal sites of involvement, activated B-cell-like (ABC) subtype, MYC expression, and MYC/BCL2 expression. Expression of pSTAT3 predicted inferior overall...

  9. Large Scale-Invariant Fluctuations in Normal Blood Cell Counts A sign of criticality?

    CERN Document Server

    Perazzo, C A; Chialvo, D R; Willshaw, P; Perazzo, Carlos A.; Fernandez, Elmer A.; Chialvo, Dante R.; Willshaw, Peter

    2000-01-01

    All types of blood cells are formed by differentiation from a small self-maintaining population of pluri-potential stem cells in the bone marrow. Despite abundant information on the molecular aspects of division, differentiation, commitment and maturation of these cells, comparatively little is known about the dynamics of the system as a whole, and how it works to maintain this complex ``ecology'' in the observed normal ranges throughout life. Here we report unexpected large, scale-free, fluctuations detected from the first long-term analysis of the day-to-day variability of a healthy animal's blood cell counts measured over one thousand days. This scale-invariance cannot be accounted for by current theoretical models, and resembles some of the scenarios described for self-organized criticality.

  10. FEM simulations and experimental studies of the temperature field in a large diamond crystal growth cell

    Institute of Scientific and Technical Information of China (English)

    Li Zhan-Chang; Jia Xiao-Peng; Huang Guo-Feng; Hu Mei-Hua; Li Yong; Yan Bing-Min; Ma Hong-An

    2013-01-01

    We investigate the temperature field variation in the growth region of a diamond crystal in a sealed cell during the whole process of crystal growth by using the temperature gradient method (TGM) at high pressure and high temperature (HPHT).We employ both the finite element method (FEM) and in situ experiments.Simulation results show that the temperature in the center area of the growth cell continues to decrease during the process of large diamond crystal growth.These results are in good agreement with our experimental data,which demonstrates that the finite element model can successfully predict the temperature field variations in the growth cell.The FEM simulation will be useful to grow larger high-quality diamond crystal by using the TGM.Furthermore,this method will be helpful in designing better cells and improving the growth process of gem-quality diamond crystal.

  11. FEM simulations and experimental studies of the temperature field in a large diamond crystal growth cell

    International Nuclear Information System (INIS)

    We investigate the temperature field variation in the growth region of a diamond crystal in a sealed cell during the whole process of crystal growth by using the temperature gradient method (TGM) at high pressure and high temperature (HPHT). We employ both the finite element method (FEM) and in situ experiments. Simulation results show that the temperature in the center area of the growth cell continues to decrease during the process of large diamond crystal growth. These results are in good agreement with our experimental data, which demonstrates that the finite element model can successfully predict the temperature field variations in the growth cell. The FEM simulation will be useful to grow larger high-quality diamond crystal by using the TGM. Furthermore, this method will be helpful in designing better cells and improving the growth process of gem-quality diamond crystal. (electromagnetism, optics, acoustics, heat transfer, classical mechanics, and fluid dynamics)

  12. A phenomenological approach to the simulation of metabolism and proliferation dynamics of large tumour cell populations

    CERN Document Server

    Chignola, R; Chignola, Roberto; Milotti, Edoardo

    2005-01-01

    A major goal of modern computational biology is to simulate the collective behaviour of large cell populations starting from the intricate web of molecular interactions occurring at the microscopic level. In this paper we describe a simplified model of cell metabolism, growth and proliferation, suitable for inclusion in a multicell simulator, now under development (Chignola R and Milotti E 2004 Physica A 338 261-6). Nutrients regulate the proliferation dynamics of tumor cells which adapt their behaviour to respond to changes in the biochemical composition of the environment. This modeling of nutrient metabolism and cell cycle at a mesoscopic scale level leads to a continuous flow of information between the two disparate spatiotemporal scales of molecular and cellular dynamics that can be simulated with modern computers and tested experimentally.

  13. Recent Advances in Aggressive Large B-cell Lymphomas: A Comprehensive Review.

    Science.gov (United States)

    Korkolopoulou, Penelope; Vassilakopoulos, Theodoros; Milionis, Vassilios; Ioannou, Maria

    2016-07-01

    Diffuse large B-cell lymphoma (DLBCL) is an aggressive disease with considerable heterogeneity reflected in the 2008 World Health Organization classification. In recent years, genome-wide assessment of genetic and epigenetic alterations has shed light upon distinct molecular subsets linked to dysregulation of specific genes or pathways. Besides fostering our knowledge regarding the molecular complexity of DLBCL types, these studies have unraveled previously unappreciated genetic lesions, which may be exploited for prognostic and therapeutic purposes. Following the last World Health Organization classification, we have witnessed the emergence of new variants of specific DLBCL entities, such as CD30 DLBCL, human immunodeficiency virus-related and age-related variants of plasmablastic lymphoma, and EBV DLBCL arising in young patients. In this review, we will present an update on the clinical, pathologic, and molecular features of DLBCL incorporating recently gained information with respect to their pathobiology and prognosis. We will emphasize the distinctive features of newly described or emerging variants and highlight advances in our understanding of entities presenting a diagnostic challenge, such as T-cell/histiocyte-rich large B-cell lmphoma and unclassifiable large B-cell lymphomas. Furthermore, we will discuss recent advances in the genomic characterization of DLBCL, as they may relate to prognostication and tailored therapeutic intervention. The information presented in this review derives from English language publications appearing in PubMed throughout December 2015. For a complete outline of this paper, please visit: http://links.lww.com/PAP/A12. PMID:27271843

  14. Massive transcriptional perturbation in subgroups of diffuse large B-cell lymphomas.

    Directory of Open Access Journals (Sweden)

    Maciej Rosolowski

    Full Text Available Based on the assumption that molecular mechanisms involved in cancerogenesis are characterized by groups of coordinately expressed genes, we developed and validated a novel method for analyzing transcriptional data called Correlated Gene Set Analysis (CGSA. Using 50 extracted gene sets we identified three different profiles of tumors in a cohort of 364 Diffuse large B-cell (DLBCL and related mature aggressive B-cell lymphomas other than Burkitt lymphoma. The first profile had high level of expression of genes related to proliferation whereas the second profile exhibited a stromal and immune response phenotype. These two profiles were characterized by a large scale gene activation affecting genes which were recently shown to be epigenetically regulated, and which were enriched in oxidative phosphorylation, energy metabolism and nucleoside biosynthesis. The third and novel profile showed only low global gene activation similar to that found in normal B cells but not cell lines. Our study indicates novel levels of complexity of DLBCL with low or high large scale gene activation related to metabolism and biosynthesis and, within the group of highly activated DLBCLs, differential behavior leading to either a proliferative or a stromal and immune response phenotype.

  15. Highly efficient and large-scale generation of functional dopamine neurons from human embryonic stem cells.

    Science.gov (United States)

    Cho, Myung Soo; Lee, Young-Eun; Kim, Ji Young; Chung, Seungsoo; Cho, Yoon Hee; Kim, Dae-Sung; Kang, Sang-Moon; Lee, Haksup; Kim, Myung-Hwa; Kim, Jeong-Hoon; Leem, Joong Woo; Oh, Sun Kyung; Choi, Young Min; Hwang, Dong-Youn; Chang, Jin Woo; Kim, Dong-Wook

    2008-03-01

    We developed a method for the efficient generation of functional dopaminergic (DA) neurons from human embryonic stem cells (hESCs) on a large scale. The most unique feature of this method is the generation of homogeneous spherical neural masses (SNMs) from the hESC-derived neural precursors. These SNMs provide several advantages: (i) they can be passaged for a long time without losing their differentiation capability into DA neurons; (ii) they can be coaxed into DA neurons at much higher efficiency than that from previous reports (86% tyrosine hydroxylase-positive neurons/total neurons); (iii) the induction of DA neurons from SNMs only takes 14 days; and (iv) no feeder cells are required during differentiation. These advantages allowed us to obtain a large number of DA neurons within a short time period and minimized potential contamination of unwanted cells or pathogens coming from the feeder layer. The highly efficient differentiation may not only enhance the efficacy of the cell therapy but also reduce the potential tumor formation from the undifferentiated residual hESCs. In line with this effect, we have never observed any tumor formation from the transplanted animals used in our study. When grafted into a parkinsonian rat model, the hESC-derived DA neurons elicited clear behavioral recovery in three behavioral tests. In summary, our study paves the way for the large-scale generation of purer and functional DA neurons for future clinical applications. PMID:18305158

  16. Fabrication of pixilated architecture large panel organic flexible solar cell by reducing bulk electrical resistance

    Science.gov (United States)

    Panag, Jasmeet Singh

    This study investigates experimentally the photovoltaic behavior and performance of a new pixilated architecture of large organic photovoltaic panels made of a large array of high-aspect ratio three-dimensional pillars surrounded by a matrix of polymer photoactive material. A least addressed problem in organic and thin-film solar cells is the high bulk resistance of cathodic and anodic layers that result in drastic reduction of currents and power conversion efficiency (PCE). For such panels to be practical and commercially competitive, this huge bulk-resistance has to be minimized as much as possible. In this study, therefore, we introduce a new novel architecture that essentially compartmentalizes large panels into smaller modules that are connected to each other in a parallel fashion. In this architecture, the metal cathode layer is applied on the top as a series of lines whereas the anodic layer is independently connected to the pixilated cells at the bottom. As a result, these modules act like independent pixel cells wherein the damage from process and operation is limited individual pixel cells. The factors considered in validating the pixilated architecture presented here consisted of effect of number of pixels on efficiency and bulk electrical resistance. In addition, the study shows that pixilated architecture offers more uniform photoactive layers, and hence better photovoltaic performance because of the compartmentalization.

  17. 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)

  18. 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.)

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

    Directory of Open Access Journals (Sweden)

    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.

  20. Unusual immunophenotype of T-cell large granular lymphocytic leukemia: Report of two cases

    Directory of Open Access Journals (Sweden)

    Nikhil Rabade

    2015-01-01

    Full Text Available Large granular lymphocytes (LGL leukemias are commonly of the T-cell or NK-cell type. T-cell LGL leukemia is typically a disorder of mature CD3, CD8 and T-cell receptor TCR (TCR - T cell receptor-αβ positive cytotoxic T-cells. Rare variants include TCRγδ+ variants and CD4 + TCRαβ+ cases. We report a case of each of these rare variants. An 83-year-old female presented with anemia and lymphocytosis with LGLs on peripheral smear. Six-color multiparametric flowcytometric analysis showed expression of CD3, heterogeneous CD7, dim CD2 and TCRγδ and lacked expression of CD5, TCRαβ, CD56, CD4 and CD8. A final diagnosis of TCRγδ+ T-cell LGL leukemia was made. Differentiation between TCRγδ+ T-cell LGL leukemia and other γδ+ T-cell malignancies is of utmost importance due to the indolent nature of the former as compared to the highly aggressive behavior of the latter. An 85-year-old male diagnosed with liposarcoma was identified to have lymphocytosis during preoperative evaluation. Peripheral smear showed presence of LGLs. Flowcytometric immunophenotyping showed expression of TCRαβ, CD3, CD2, CD5, CD4, dim CD8, CD56 with aberrant loss of CD7 expression. Vβ repertoire analysis by flowcytometry showed 97% cells with Vβ14 clonality. A final diagnosis of TCRαβ+ CD4 + T-cell LGL leukemia was made. CD4 + T-cell large granular lymphocytic leukemias have an indolent, less aggressive course when compared to their CD8 + counterparts and are not necessarily associated with cytopenias. However, their association with secondary neoplasia (29% of the cases warrants a high degree of suspicion in the diagnosis as also noted in the index case. Use of a wide panel of antibodies and newer modalities such as Vβ repertoire analysis helps in accurate subtyping of LGL leukemia.

  1. Primary cutaneous diffuse large B-cell lymphoma of the upper limb: A fascinating entity

    Directory of Open Access Journals (Sweden)

    Manoj Madakshira Gopal

    2013-01-01

    Full Text Available Primary cutaneous lymphomas are defined as lymphoid neoplasms that present themselves clinically on the skin and do not have extra-cutaneous disease, when the diagnosis is made or even after 6 months of the diagnosis. Primary cutaneous lymphomas of B-cells are less frequent than lymphomas of T-cells. Primary B-cell lymphomas have a better prognosis than secondary B-cell lymphomas. Primary B-cell cutaneous lymphomas are classified into five types according to the World Health Organization and European Organization for Research and Treatment of Cancer classification. The primary diffuse large B-cell cutaneous lymphoma - leg type corresponds to approximately 5-10% of the B-cell cutaneous lymphomas. It is predominantly seen in elderly people and has a female preponderance. Skin lesions can be single, multiple, and even grouped. A 5-year survival rate ranges from 36 to 100% of the cases. The expression of Bcl-2, presence of multiple lesions, and involvement of both the upper limbs lead to a worse prognosis. Very few cases have been described in the literature.

  2. Alisertib in Combination With Vorinostat in Treating Patients With Relapsed or Recurrent Hodgkin Lymphoma, B-Cell Non-Hodgkin Lymphoma, or Peripheral T-Cell Lymphoma

    Science.gov (United States)

    2016-07-12

    Adult B Acute Lymphoblastic Leukemia; Adult T Acute Lymphoblastic Leukemia; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-Cell Lymphoma; Chronic Lymphocytic Leukemia; Cutaneous B-Cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Hepatosplenic T-Cell Lymphoma; Intraocular Lymphoma; Lymphomatous Involvement of Non-Cutaneous Extranodal Site; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Nodal Marginal Zone Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-Cell Leukemia/Lymphoma; Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides and Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestinal Lymphoma; Splenic Marginal Zone Lymphoma; T-Cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenstrom Macroglobulinemia

  3. Large cell neuroendocrine carcinoma (LCNEC of the urinary bladder: a case report

    Directory of Open Access Journals (Sweden)

    Colarossi Cristina

    2013-02-01

    Full Text Available Abstract Neuroendocrine carcinoma of the urinary bladder is a rare entity, accounting less then 1% of urinary bladder malignancies. The vast majority of the neuroendocrine carcinoma of the urinary bladder is represented by small cell neuroendocrine carcinoma while just few cases of large cell neuroendocrine carcinoma (LCNEC have been reported. In this cases report we describe a rare case of primary bladder LCNEC. Virtual Slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2474700528951562.

  4. Primary uterine diffuse large B-cell lymphoma involving the urinary bladder with urinary cytology mimicking carcinomas: A case report

    OpenAIRE

    Sumiyo Adachi; Kazuto Yamazaki; Shan-Guang Liang; Yasuo Ishida

    2015-01-01

    We report a rare case of a 69-year-old woman in whom diffuse large B-cell lymphoma (DLBCL) originated from the uterus and involved the urinary bladder. The cervical smears of the case mostly consisted of discohesive atypical round cells, which were highly suggestive of lymphoma; however, in voided urine smears, a majority of the cells formed large aggregates of degenerated cells, mimicking those of urothelial carcinoma (UC). The smears also represented some small loose clusters, in which tumo...

  5. Origin of the high performance of perovskite solar cells with large grains

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Jian; Shi, Tongfei, E-mail: tongfeishi@gmail.com; Li, Xinhua; Zhou, Bukang; Cao, Huaxiang; Wang, Yuqi [Key Laboratory of Materials Physics, Institute of Solid State Physics, Chinese Academy of Sciences, Hefei 230031 (China)

    2016-02-01

    Due to excellent carrier transport characteristics, CH{sub 3}NH{sub 3}PbI{sub 3} film made of large single crystal grains is considered as a key to improve upon already remarkable perovskite solar cell (PSC) efficiency. We have used a simple and efficient solvent vapor annealing method to obtain CH{sub 3}NH{sub 3}PbI{sub 3} films with grain size over 1 μm. PSCs with different grain size films have been fabricated and verified the potential of large grains for improving solar cells performance. Moreover, the larger grain films have shown stronger light absorption ability and more photon-generated carriers under the same illumination. A detailed temperature-dependent PL study has indicated that it originates from larger radius and lower binding energy of donor-acceptor-pair (DAP) in larger grains, which makes the DAP is easily to be separated and difficult to be recombine.

  6. Development of polymers for large scale roll-to-roll processing of polymer solar cells

    DEFF Research Database (Denmark)

    Carlé, Jon Eggert

    platform for polymer development. PSC devices based on PDTSTTz-4 and PCBM were produced using the laboratory roll coater and through optimerization of the processing parameters a PCE of 2.95 % at ambient condition. This efficiency is among the highest obtained on flexible ITO-free substrates using slot......Development of polymers for large scale roll-to-roll processing of polymer solar cells Conjugated polymers potential to both absorb light and transport current as well as the perspective of low cost and large scale production has made these kinds of material attractive in solar cell research. The...... and how this affects the PSC parameters are presented. It is generally found that it is possible to synthetically control the absorption spectrum of conjugated polymer systems. One way to alter the spectrum is by incorporating alternating donor-acceptor motifs, resulting in an additional optical...

  7. Diffuse large B-cell lymphoma of the ocular adnexal region

    DEFF Research Database (Denmark)

    Rasmussen, Peter Kristian; Ralfkiaer, Elisabeth; Prause, Jan U;

    2013-01-01

    Purpose: To characterize the clinicopathological features of diffuse large B-cell lymphoma (DLBCL) of the ocular adnexal region. Methods: The present series of orbital and adnexal DLBCLs were found by searching the Danish Registry of Pathology between 1980 and 2009. Histological specimens were re......-evaluated using a panel of monoclonal antibodies. Clinical files from all patients with confirmed DLBCL were collected. Results: A total of 34 patients with DLBCL of the ocular adnexal region were identified. Eighteen of the patients were men. The patients had a median age of 78 years (range 35-97 years). Ninety......, concordant bone marrow involvement and the International Prognostic Index (IPI) score were prognostic factors for OS. Conclusions: Diffuse large B-cell lymphoma of the ocular adnexal region is mainly prevalent in elderly patients. Most patients had unilateral orbital involvement. The overall prognosis is...

  8. Origin of the high performance of perovskite solar cells with large grains

    International Nuclear Information System (INIS)

    Due to excellent carrier transport characteristics, CH3NH3PbI3 film made of large single crystal grains is considered as a key to improve upon already remarkable perovskite solar cell (PSC) efficiency. We have used a simple and efficient solvent vapor annealing method to obtain CH3NH3PbI3 films with grain size over 1 μm. PSCs with different grain size films have been fabricated and verified the potential of large grains for improving solar cells performance. Moreover, the larger grain films have shown stronger light absorption ability and more photon-generated carriers under the same illumination. A detailed temperature-dependent PL study has indicated that it originates from larger radius and lower binding energy of donor-acceptor-pair (DAP) in larger grains, which makes the DAP is easily to be separated and difficult to be recombine

  9. Fabrication of large area silicon solar cells by rapid thermal processing

    Science.gov (United States)

    Sivoththaman, S.; Laureys, W.; Nijs, J.; Mertens, R.

    1995-10-01

    Large area n+pp+ solar cells have been fabricated on 10 cm×10 cm pseudo-quasi-square CZ silicon wafers (1 Ω cm, p-type) predominantly used by the photovoltaic (PV) industry. All the high-temperature steps have been performed by rapid thermal processing (RTP). Emitter formation, back surface field (BSF) formation, and surface oxidation have been performed in just two RTP steps each lasting 50 s. Solar cells of 15% efficiency have been fabricated this way, demonstrating the applicability of this low thermal budget technology to large area, modulable size, industrial quality Si wafers. Furthermore, the rapid thermal oxidation (RTO) is shown to result in good quality thin oxides with Si/SiO2 interface trap densities (Dit)<1011 cm-3 eV-1 near-midgap.

  10. Intravascular large B-cell lymphoma complicated by invasive pulmonary aspergillosis: a rare presentation

    Science.gov (United States)

    Mahasneh, Tamadur; Harrington, Zinta; Williamson, Jonathan; Alkhawaja, Darweesh; Duflou, Jo; Shin, Joo-Shik

    2014-01-01

    We describe a patient with persisting fevers, a progressive pulmonary infiltrate, and high levels of serum lactate dehydrogenase. No underlying cause for these changes was found prior to her death despite extensive investigations. Postmortem tissue revealed invasive pulmonary aspergillosis and subsequent brain examination revealed vascular changes in keeping with intravascular large B-cell lymphoma (IVLBCL). On review, subtle yet extensive lymphomatous infiltrates involved the vasculature of multiple other organs, including the lungs. Aspergillosis is a relatively rare presenting feature of lymphoproliferative disorders, and IVLBCL is a rare subtype of diffuse large B-cell non-Hodgkin's lymphoma with, to our knowledge, very few case reports to date. Lymphoma should be considered in patients presenting with pneumonitis with bilateral lung infiltrates on imaging, with a high serum level of lactate dehydrogenase. PMID:25473570

  11. Intravascular Large B-Cell Lymphoma Presenting as Interstitial Lung Disease

    Directory of Open Access Journals (Sweden)

    Elham Vali Khojeini

    2014-01-01

    Full Text Available Intravascular large B-cell lymphoma (IVLBL is a rare subtype of diffuse large B-cell lymphoma that resides in the lumen of blood vessels. Patients typically present with nonspecific findings, particularly bizarre neurologic symptoms, fever, and skin lesions. A woman presented with shortness of breath and a chest CT scan showed diffuse interstitial thickening and ground glass opacities suggestive of an interstitial lung disease. On physical exam she was noted to have splenomegaly. The patient died and at autopsy was found to have an IVLBL in her lungs as well as nearly all her organs that were sampled. Although rare, IVLBL should be included in the differential diagnosis of interstitial lung disease and this case underscores the importance of the continuation of autopsies.

  12. Condensation by DNA looping facilitates transfer of large DNA molecules into mammalian cells

    OpenAIRE

    Montigny, William J.; Houchens, Christopher R.; Illenye, Sharon; Gilbert, Jonathan; Coonrod, Emily; Chang, Young-Chae; Nicholas H. Heintz

    2001-01-01

    Experimental studies of complete mammalian genes and other genetic domains are impeded by the difficulty of introducing large DNA molecules into cells in culture. Previously we have shown that GST–Z2, a protein that contains three zinc fingers and a proline-rich multimerization domain from the polydactyl zinc finger protein RIP60 fused to glutathione S-transferase (GST), mediates DNA binding and looping in vitro. Atomic force microscopy showed that GST–Z2 is able to condense 1...

  13. P11.09A NEUROLOGIC PRESENTATION OF INTRAVASCULAR LARGE B-CELL LYMPHOMA

    OpenAIRE

    Matas, A.F.M.R.; Veiga, A.S.B.T.; Gabriel, J.P.M.S.; Silva, M. R.

    2014-01-01

    INTRODUCTION: Intravascular large B-cell lymphoma is a rare and fatal disease that can have central nervous system manifestations. Given its rarity and the multiplicity of presentations, diagnosis is extremely difficult. We report a case that presented with neurological manifestations and which diagnosis was made ante mortem. CASE REPORT: A 74-year-old man, with a background of hypertension and dyslipidemia was referred to our neurology department with a history of speech difficulties and wal...

  14. Gene expression-based risk score in diffuse large B-cell lymphoma.

    OpenAIRE

    Bret, Caroline; Klein, Bernard; Moreaux, Jérôme

    2012-01-01

    International audience Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma and displays heterogeneous clinical and molecular characteristics. In this study, high throughput gene expression profiling of DLBCL tumor samples was used to design a 12-gene expression-based risk score (GERS) predictive for patient's overall survival. GERS allowed identifying a high-risk group comprising 46,4% of the DLBCL patients in two independent cohorts (n=414 and n=69). GERS...

  15. Highly efficient and large-scale generation of functional dopamine neurons from human embryonic stem cells

    OpenAIRE

    Cho, Myung Soo; Lee, Young-Eun; Kim, Ji Young; Chung, Seungsoo; Cho, Yoon Hee; Kim, Dae-Sung; Kang, Sang-Moon; Lee, Haksup; Kim, Myung-Hwa; Kim, Jeong-Hoon; Leem, Joong Woo; Oh, Sun Kyung; Choi, Young Min; Hwang, Dong-Youn; Chang, Jin Woo

    2008-01-01

    We developed a method for the efficient generation of functional dopaminergic (DA) neurons from human embryonic stem cells (hESCs) on a large scale. The most unique feature of this method is the generation of homogeneous spherical neural masses (SNMs) from the hESC-derived neural precursors. These SNMs provide several advantages: (i) they can be passaged for a long time without losing their differentiation capability into DA neurons; (ii) they can be coaxed into DA neurons at much higher effi...

  16. Intravascular large B-cell lymphoma complicated by invasive pulmonary aspergillosis: a rare presentation

    OpenAIRE

    Mahasneh, Tamadur; Harrington, Zinta; Williamson, Jonathan; Alkhawaja, Darweesh; Duflou, Jo; Shin, Joo-Shik

    2014-01-01

    We describe a patient with persisting fevers, a progressive pulmonary infiltrate, and high levels of serum lactate dehydrogenase. No underlying cause for these changes was found prior to her death despite extensive investigations. Postmortem tissue revealed invasive pulmonary aspergillosis and subsequent brain examination revealed vascular changes in keeping with intravascular large B-cell lymphoma (IVLBCL). On review, subtle yet extensive lymphomatous infiltrates involved the vasculature of ...

  17. Zosteriform Secondary Cutaneous Diffuse Large B-Cell Lymphoma on FDG PET/CT.

    Science.gov (United States)

    Liao, Chiung-Wei; Yen, Kuo-Yang; Hsieh, Te-Chun; Kao, Chia-Hung

    2016-09-01

    We present a case of a woman who had erythematous papules on the abdomen accompanied with numbness and local heat sensation. She had received chemotherapy for advanced follicular lymphoma. F-FDG PET/CT demonstrated band-like hypermetabolic lesions seemingly involving dermatomes of lower abdominal wall, which was confirmed as secondary cutaneous diffuse large B-cell lymphoma via skin biopsy. PMID:27405036

  18. Gamma-secretase inhibition combined with platinum compounds enhances cell death in a large subset of colorectal cancer cells

    Directory of Open Access Journals (Sweden)

    Feller Stephan M

    2008-10-01

    Full Text Available Abstract Background Notch signalling is essential for the development and maintenance of the colonic epithelium. Its inhibition induces a differentiation phenotype in vivo and reduces adenomas in APCmin mice. Whether Notch signals are also required in colorectal cancer (CRC has remained elusive. Therefore, 64 CRC cell lines were analysed for the occurrence of proteolytically processed, active Notch. Results 63 CRC lines contained a fragment with approximately the size of the Notch1 intracellular domain (NICD, which is required for signalling. Subsequent analyses with an antibody that specifically recognises the free Val1744 residue generated by γ-secretase-mediated cleavage of Notch1 showed that a subset of CRC cells lacks this specific Val1744-NICD. Surprisingly, inhibition of Val1744-NICD signalling with different γ-secretase inhibitors (GSI did not lead to substantial effects on CRC cell line growth or survival. However, transient activation of Erk upon GSI treatment was detected. Since cisplatin relies on Erk activation for bioactivity in some cells, platinum compounds were tested together with GSI and enhanced cell killing in a subset of Val1744-NICD-positive CRC cell lines was detected. Erk inhibition ablated this combination effect. Conclusion We conclude that γ-secretase inhibition results in activation of the MAP kinases Erk1/2 and, when used in conjunction, enhances cell death induced by platinum compounds in a large subset of colorectal cancer cell lines. Furthermore the activation of Erk appears to be of particular importance in mediating the enhanced effect seen, as its inhibition abrogates the observed phenomenon. These findings do not only highlight the importance of signalling pathway crosstalk but they may also suggest a new avenue of combination therapy for some colorectal cancers.

  19. Fludarabine Phosphate, Melphalan, and Low-Dose Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies

    Science.gov (United States)

    2015-10-28

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Grade III Lymphomatoid Granulomatosis; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Aplastic Anemia; Burkitt Lymphoma; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Grade III Lymphomatoid Granulomatosis; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Congenital Amegakaryocytic Thrombocytopenia; Diamond-Blackfan Anemia; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Juvenile Myelomonocytic Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Paroxysmal Nocturnal Hemoglobinuria; Peripheral T-cell Lymphoma; Polycythemia Vera; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell

  20. Sulfated glycosaminoglycans in cultured endothelial cells from capillaries and large vessels of human and bovine origin

    International Nuclear Information System (INIS)

    The (35S)glycosaminoglycans ((35S)GAG) synthesized by capillary endothelial cells were analyzed and compared to GAG synthesized by endothelial cells cultured from 4 larger vessels. Two separate cultures of endothelial cells were established from bovine fat capillaries and from 4 larger vessels of human origin (umbilical vein) and bovine origin (pulmonary artery, pulmonary vein and aorta). After incubation with 35SO4 for 72 h, the (35S)glycosaminoglycans (GAG) composition of the media, pericellular and cellular fractions of each culture were determined by selective degradation with nitrous acid, chondroitinase ABC and chondroitinase AC. All endothelial cells produced large amounts of (35S)GAG with increased proportions of heparinoids (heparan sulfate and heparin) in the cellular and pericellular fractions. Each culture showed a distinct distribution of (35S)GAG in the media, pericellular and cellular fractions with several specific differences found among the 5 cultures. The differences in GAG content were confirmed in a second group of separate cultures from each of the 5 vessels indicating that, although having several features of GAG metabolism in common, each endothelial cell culture demonstrated a characteristic complement of synthesized, secreted and cell surface-sulfated glycosaminoglycans. (author)

  1. Addition of lysophospholipids with large head groups to cells inhibits Shiga toxin binding.

    Science.gov (United States)

    Ailte, Ieva; Lingelem, Anne Berit Dyve; Kavaliauskiene, Simona; Bergan, Jonas; Kvalvaag, Audun Sverre; Myrann, Anne-Grethe; Skotland, Tore; Sandvig, Kirsten

    2016-01-01

    Shiga toxin (Stx), an AB5 toxin, binds specifically to the neutral glycosphingolipid Gb3 at the cell surface before being transported into cells. We here demonstrate that addition of conical lysophospholipids (LPLs) with large head groups inhibit Stx binding to cells whereas LPLs with small head groups do not. Lysophosphatidylinositol (LPI 18:0), the most efficient LPL with the largest head group, was selected for in-depth investigations to study how the binding of Stx is regulated. We show that the inhibition of Stx binding by LPI is reversible and possibly regulated by cholesterol since addition of methyl-β-cyclodextrin (mβCD) reversed the ability of LPI to inhibit binding. LPI-induced inhibition of Stx binding is independent of signalling and membrane turnover as it occurs in fixed cells as well as after depletion of cellular ATP. Furthermore, data obtained with fluorescent membrane dyes suggest that LPI treatment has a direct effect on plasma membrane lipid packing with shift towards a liquid disordered phase in the outer leaflet, while lysophosphoethanolamine (LPE), which has a small head group, does not. In conclusion, our data show that cellular treatment with conical LPLs with large head groups changes intrinsic properties of the plasma membrane and modulates Stx binding to Gb3. PMID:27458147

  2. 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.

  3. Mixed Large Cell Neuroendocrine Carcinoma and Adenocarcinoma with Spindle Cell and Clear Cell Features in the Extrahepatic Bile Duct

    OpenAIRE

    John Wysocki; Rishi Agarwal; Laura Bratton; Jeremy Nguyen; Mandy Crause Weidenhaft; Nathan Shores; Kimbrell, Hillary Z.

    2014-01-01

    Mixed adenoneuroendocrine carcinomas, spindle cell carcinomas, and clear cell carcinomas are all rare tumors in the biliary tract. We present the first case, to our knowledge, of an extrahepatic bile duct carcinoma composed of all three types. A 65-year-old man with prior cholecystectomy presented with painless jaundice, vomiting, and weight loss. CA19-9 and alpha-fetoprotein (AFP) were elevated. Cholangioscopy revealed a friable mass extending from the middle of the common bile duct to the c...

  4. Different sensitivity of germinal center B cell-like diffuse large B cell lymphoma cells towards ibrutinib treatment

    OpenAIRE

    Zheng, Xiaohui; Ding, Ning; Song, Yuqin; Feng, Lixia; Zhu, Jun

    2014-01-01

    Background Although rituximab in the combination of CHOP chemotherapy has been widely used as the standard treatment for several kinds of B-cell non-Hodgkin lymphoma (B-NHL), a great number of B-NHL patients treated with this immunotherapy still develop primary and secondary resistance. Recently Bruton’s tyrosine kinase (Btk) inhibitor ibrutinib showed promising therapeutic effect in relapsed/refractory CLL and B-cell NHL, which provided essential alternatives for these patients. Methods The ...

  5. Diffuse large cell lymphoma and colon adenocarcinoma in patient with Waldenström’s macroglobulinaemia

    Directory of Open Access Journals (Sweden)

    Radojković Milica

    2011-01-01

    Full Text Available Introduction. Waldenström’s macroglobulinaemia is a rare B cell lymphoproliferative disorder characterized by lymphoplasmocyte bone marrow infiltration and monoclonal IgM gammopathy. In the majority of cases, Waldenström’s macroglobulinaemia is a chronic disease with variable course. Therapy consists of alkylating agents, purine analogs and antiCD20 monoclonal antibody. In the literature, there have been descriptions of rare cases of progression of Waldenström’s macroglobulinaemia to aggressive lymphoma, as well as secondary carcinoma in the patients after treatment of macroglobulinaemia. Case Outline. A 63-year-old patient was diagnosed with serum monoclonal IgM kappa gammopathy (Waldenström’s macroglobulinaemia. Chemotherapy was applied and a good clinical and haematological response had been achieved. Ten years later, the patient was diagnosed with colon adenocarcinoma as a secondary malignancy, and operated on. Within one month, the patient rapidly developed a large neck tumour mass. Tumour biopsy revealed the diagnosis of diffuse large B cell lymphoma with the expression of monoclonal lambda chain, which more likely pointed out to coexistence of two different B cell lymphoproliferative disorders, rather than the transformation of Waldenström’s macroglobulinaemia to aggressive lymphoma. The patient was treated with chemotherapy following R-CHOP protocol, and clinical remission was achieved. Seven months later, despite the successful treatment of lymphoproliferative disorder, dissemination of adenocarcinoma led to the lethal outcome. Conclusion. The patient was diagnosed with a rare occurrence of three neoplastic diseases: Waldenström’s macroglobulinaemia, colon adenocarcinoma and diffuse large B cell lymphoma. The possible mechanisms of the combined appearance of lymphoproliferative and other malignant diseases include the previous treatment with alkylating agents, genetic, immunomodulatory and environmental factors.

  6. Oral Manifestations of T-Cell Large Granular Lymphocytic Leukemia: a Case Report

    Directory of Open Access Journals (Sweden)

    Ioanna-Eirini Arvanitidou

    2011-06-01

    Full Text Available Background: T-cell large granular lymphocytic (T-LGL leukemia is a rare, chronic, often indolent lymphoproliferative disorder of mature T cells (CD3+. Severe neutropenia and other cytopenias are common features in patients with T-LGL leukemia and may cause infections, thus representing a major cause of morbidity in this disease. Immunosuppressive therapy with low-dose regimes of methotrexate, cyclophosphamide, corticosteroids or cyclosporine A is the treatment of choice. Amongst the variety of T-LGL leukemia complications, oral manifestations such as ulcers have been rarely reported. The purpose of this paper is to report a case of T-cell large granular lymphocyte leukemia with oral manifestations and to discuss their pathogenesis and management.Methods: In the present case, a 65 year old female with a two-month history of diagnosed T-LGL leukemia presented with oral lesions, including ulcerations on the ventral tongue and soft palate as well as swollen, erythematous and ulcerated gingiva. The patient was under treatment with methotrexate, granulocyte colony-stimulating factor (G-CSF and erythropoietin.Results: Considering patients’ medical history and clinical appearance of the lesions, a clinical diagnosis of a neutropenic ulcer of the tongue was established. The oral lesions resolved after treatment with antibiotics, topical steroids and antiseptics combined with improvement of the hematological condition. The pertinent literature related to T-LGL leukemia ethiopathology, diagnostics and treatment was discussed.Conclusions: Although rare, T-cell large granular lymphocytic leukemia should be included in the list of lymphoproliferative disorders, which may present with oral manifestations as a result of the disease and its treatment complications.

  7. {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.)

  8. 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.)

  9. Performance Improvements of Selective Emitters by Laser Openings on Large-Area Multicrystalline Si Solar Cells

    Directory of Open Access Journals (Sweden)

    Sheng-Shih Wang

    2014-01-01

    Full Text Available This study focuses on the laser opening technique used to form a selective emitter (SE structure on multicrystalline silicon (mc-Si. This technique can be used in the large-area (156 × 156 mm2 solar cells. SE process of this investigation was performed using 3 samples SE1–SE3. Laser fluences can vary in range of 2–5 J/cm2. The optimal conversion efficiency of 15.95% is obtained with the SE3 (2 J/cm2 fluence after laser opening with optimization of heavy and light dopant, which yields a gain of 0.48%abs compared with that of a reference cell (without fluence. In addition, this optimal SE3 cell displays improved characteristics compared with other cells with a higher average value of external quantum efficiency (EQEavg = 68.6% and a lower average value of power loss (Ploss = 2.33 mW/cm2. For the fabrication of solar cells, the laser opening process comprises fewer steps than traditional photolithography does. Furthermore, the laser opening process decreases consumption of chemical materials; therefore, the laser opening process decreases both time and cost. Therefore, SE process is simple, cheap, and suitable for commercialization. Moreover, the prominent features of the process render it effective means to promote overall performance in the photovoltaic industry.

  10. Artificial membrane-binding proteins stimulate oxygenation of stem cells during engineering of large cartilage tissue

    Science.gov (United States)

    Armstrong, James P. K.; Shakur, Rameen; Horne, Joseph P.; Dickinson, Sally C.; Armstrong, Craig T.; Lau, Katherine; Kadiwala, Juned; Lowe, Robert; Seddon, Annela; Mann, Stephen; Anderson, J. L. Ross; Perriman, Adam W.; Hollander, Anthony P.

    2015-06-01

    Restricted oxygen diffusion can result in central cell necrosis in engineered tissue, a problem that is exacerbated when engineering large tissue constructs for clinical application. Here we show that pre-treating human mesenchymal stem cells (hMSCs) with synthetic membrane-active myoglobin-polymer-surfactant complexes can provide a reservoir of oxygen capable of alleviating necrosis at the centre of hyaline cartilage. This is achieved through the development of a new cell functionalization methodology based on polymer-surfactant conjugation, which allows the delivery of functional proteins to the hMSC membrane. This new approach circumvents the need for cell surface engineering using protein chimerization or genetic transfection, and we demonstrate that the surface-modified hMSCs retain their ability to proliferate and to undergo multilineage differentiation. The functionalization technology is facile, versatile and non-disruptive, and in addition to tissue oxygenation, it should have far-reaching application in a host of tissue engineering and cell-based therapies.

  11. Large scale isolation of DNA repair mutants of Chinese hamster ovary cells

    International Nuclear Information System (INIS)

    A semiautomated procedure has been designed and used successfully to permit the isolation of a large number of uv (ultraviolet light) sensitive mutant colonies of Chinese hamster ovary (CHO) cells. 149 uv sensitive mutants of CHO cells have been isolated to date by this procedure. This represents the largest in vitro isolation to date of uv sensitive mutants of mammalian cells The isolation of uv sensitive clones of EM9-1 represents the first stepwise isolation of double mutants of mammalian cells with sensitivity to an increased range of carcinogenic agents. Using a rapid screening test for complementation group assignment, 70 of these mutants have been assigned to a total of 5 complementation classes. Representatives of 4 of these classes have been studied for competence in repair replication following uv irradiation and have demonstrated a defective phenotype in uv repair. Representatives of 2 of these repair-deficient classes have been studies for uv mutagenic response for three selective markers, and have demonstrated an approximately ninefold enhancement in mutant yield per unit uv exposure relative to the parental cels. The sensitivity, repair phenotype, and mutational response ofthe isolates studied resemble that of human mutant xeroderma pigmentosum cells

  12. Highly efficient industrial large-area black silicon solar cells achieved by surface nanostructured modification

    Science.gov (United States)

    Li, Ping; Wei, Yi; Zhao, Zengchao; Tan, Xin; Bian, Jiming; Wang, Yuxuan; Lu, Chunxi; Liu, Aimin

    2015-12-01

    Traditional black silicon solar cells show relatively low efficiencies due to the high surface recombination occurring at the front surfaces. In this paper, we present a surface modification process to suppress surface recombination and fabricate highly efficient industrial black silicon solar cells. The Ag-nanoparticle-assisted etching is applied to realize front surface nanostructures on silicon wafers in order to reduce the surface reflectance. Through a further tetramethylammonium hydroxide (TMAH) treatment, the carrier recombination at and near the surface is greatly suppressed, due to a lower surface dopant concentration after the surface modification. This modified surface presents a low reflectivity in a range of 350-1100 nm. Large-area solar cells with an average conversion efficiency of 19.03% are achieved by using the TMAH treatment of 30 s. This efficiency is 0.18% higher than that of standard silicon solar cells with pyramidal surfaces, and also a remarkable improvement compared with black silicon solar cells without TMAH modifications.

  13. Heat Shield Employing Cured Thermal Protection Material Blocks Bonded in a Large-Cell Honeycomb Matrix

    Science.gov (United States)

    Zell, Peter

    2012-01-01

    A document describes a new way to integrate thermal protection materials on external surfaces of vehicles that experience the severe heating environments of atmospheric entry from space. Cured blocks of thermal protection materials are bonded into a compatible, large-cell honeycomb matrix that can be applied on the external surfaces of the vehicles. The honeycomb matrix cell size, and corresponding thermal protection material block size, is envisioned to be between 1 and 4 in. (.2.5 and 10 cm) on a side, with a depth required to protect the vehicle. The cell wall thickness is thin, between 0.01 and 0.10 in. (.0.025 and 0.25 cm). A key feature is that the honeycomb matrix is attached to the vehicle fs unprotected external surface prior to insertion of the thermal protection material blocks. The attachment integrity of the honeycomb can then be confirmed over the full range of temperature and loads that the vehicle will experience. Another key feature of the innovation is the use of uniform-sized thermal protection material blocks. This feature allows for the mass production of these blocks at a size that is convenient for quality control inspection. The honeycomb that receives the blocks must have cells with a compatible set of internal dimensions. The innovation involves the use of a faceted subsurface under the honeycomb. This provides a predictable surface with perpendicular cell walls for the majority of the blocks. Some cells will have positive tapers to accommodate mitered joints between honeycomb panels on each facet of the subsurface. These tapered cells have dimensions that may fall within the boundaries of the uniform-sized blocks.

  14. 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

  15. Composite diffuse large B-cell lymphoma and follicular B-cell lymphoma - case report and review of literature.

    Science.gov (United States)

    Turbatu, Andrei; Stoian, Marilena; Brezean, Iulian; Stoica, Victor Constantin Ion; Colita, Andrei; Dobrea, Camelia; State, Nicoleta; Ionescu, Cosmin; Ivanescu, Ana-Maria; Oprea, Madalina; Ghimici, Cecilia; Lupu, Anca Roxana

    2014-06-01

    Composite lymphoma refers to the co-occurrence of two or more morphologically and immunophenotypically separate lymphomas in the same topographic site at the time of clinical presentation. It is an infrequent type of lymphoid neoplasm, present in lymphoid tissue and may be due to the existence of two genetically related neoplasms such as transformation of a single lymphoma into another more aggressive lymphoma or be due to the presence of two clonally unrelated lymphomas. This paper is presenting a case of diffuse non-Hodgkin large B-cell lymphoma with areas of low grade and high grade follicular non-Hodgkin B-cell lymphoma in a retroperitoneal lymph node and spleen of an 62 year old woman. Histopathological examination and immunohistochemistry features proved the diagnosis of composite lymphoma. PMID:25705280

  16. Composite Diffuse Large B-Cell Lymphoma and Follicular B-Cell Lymphoma – Case Report and Review of Literature

    Science.gov (United States)

    TURBATU, Andrei; STOIAN, Marilena; BREZEAN, Iulian; STOICA, Victor Constantin Ion; COLITA, Andrei; DOBREA, Camelia; STATE, Nicoleta; IONESCU, Cosmin; IVANESCU, Ana-Maria; OPREA, Madalina; GHIMICI, Cecilia; LUPU, Anca Roxana

    2014-01-01

    Composite lymphoma refers to the co-occurrence of two or more morphologically and immunophenotypically separate lymphomas in the same topographic site at the time of clinical presentation. It is an infrequent type of lymphoid neoplasm, present in lymphoid tissue and may be due to the existence of two genetically related neoplasms such as transformation of a single lymphoma into another more aggressive lymphoma or be due to the presence of two clonally unrelated lymphomas. This paper is presenting a case of diffuse non-Hodgkin large B-cell lymphoma with areas of low grade and high grade follicular non-Hodgkin B-cell lymphoma in a retroperitoneal lymph node and spleen of an 62 year old woman. Histopathological examination and immunohistochemistry features proved the diagnosis of composite lymphoma. PMID:25705280

  17. Two cases of uveitis masquerade syndrome caused by bilateral intraocular large B-cell lymphoma

    Directory of Open Access Journals (Sweden)

    Jovanović Svetlana

    2013-01-01

    Full Text Available Introduction. Sometimes it is not easy to clinically recognize subtle differences between intraocular lymphoma and noninfectious uveitis. The most common lymphoma subtype involving the eye is B-cell lymphoma. Case report. We presented two patients aged 59 and 58 years with infiltration of the subretinal space with a large B-cell non-Hodgkin intraocular lymphoma. The patients originally had clinically masked syndrome in the form of intermediate uveitis. As it was a corticosteroid-resistant uveitis, we focused on the possible diagnosis of neoplastic causes of this syndrome. During hospitalization, the neurological symptoms emerged and multiple subretinal changes accompanied by yellowish white patches of retinal pigment epithelium with signs of vitritis, which made us suspect the intraocular lymphoma. Endocranial magnetic resonance imaging established tumorous infiltration in the region of the left hemisphere of the cerebellum. The histopathological finding confirmed the diagnosis of large B-cell non-Hodgkin lymphoma of risk moderate degree, immunoblast - centroblast cytological type. The other patient had clinical chronic uveitis accompanied by yellowish shaped white echographic changes of the retina and localized changes in the level of the subretina. The diagnosis of lymphoma was made by brain biopsy. Conclusion. Uveitis masquerade syndrome should be considered in all patients over 40 years with idiopathic steroid-resistant uveitis. Treatment begun on time can affect the course and improve the prognosis of uveitis masquerade syndrome (UMS and systemic disease.

  18. Role of Immunohistochemistry in Staging Diffuse Large B-cell Lymphoma (DLBCL)

    Science.gov (United States)

    Talaulikar, Dipti; Dahlstrom, Jane Esther; Shadbolt, Bruce; Broomfield, Amy; McDonald, Anne

    2008-01-01

    The use of immunohistochemistry (IHC) in staging bone marrow in non-Hodgkin's lymphoma (NHL) is largely limited to ambiguous cases, particularly those with lymphoid aggregates. Its role in routine clinical practice remains unestablished. This study aimed to determine whether the routine use of IHC in diffuse large B-cell lymphoma (DLBCL) would improve the detection of lymphomatous involvement in the bone marrow. It also sought to determine the impact of IHC on predicting survival compared with routine histological diagnosis using hematoxylin and eosin (H&E), Giemsa, and reticulin staining. The bone marrow trephines of 156 histologically proven DLBCL cases were assessed on routine histology, and IHC using two T-cell markers (CD45RO and CD3), two B-cell markers (CD20 and CD79a), and κ and λ light chains. IHC detected lymphomatous involvement on an additional 11% cases compared with histology alone. Although both routine histology and IHC were good predictors of survival, IHC was better at predicting survival on stepwise multivariate Cox regression analysis. IHC performed routinely on bone marrow trephines has the ability to improve detection of occult lymphoma in experienced hands. Furthermore, it is a better predictor of survival compared with routine histological examination alone. (J Histochem Cytochem 56:893–900, 2008) PMID:18574254

  19. Intravascular Large B Cell Lymphoma as a Rare Cause of Reversed Halo Sign: A Case Report.

    Science.gov (United States)

    Peng, Min; Shi, Juhong; Liu, Hongrui; Li, Guangxi

    2016-03-01

    Intravascular large B cell lymphoma (IVLBCL) is a rare type of extranodal diffused large B-cell lymphoma. IVLBCL with primary lung lesion is very rare and it is very difficult to diagnose. Radiographic findings of pulmonary IVLBCL are nonspecific and resembling interstitial lung diseases. Reversed halo sign (RHS) was initially reported in patients diagnosed with cryptogenic organizing pneumonia and then described in a variety of diseases with inflammatory, infectious, autoimmune, and malignant causes. This is the first case of IVLBCL that has presented with RHSs on CT scan.A 59-year-old Chinese man presented with a 4-month history of a nonproductive cough and a weight loss of 5 kg. Physical examination was unremarkable. High-resolution computed tomography scan of the chest showed bilateral patchy ground glass opacities (GGOs) and RHSs. Laboratory tests were unremarkable except elevated serum lactate dehydrogenase (LDH). Surgical lung biopsy was performed. Light microscopic examination of the specimen disclosed diffuse alveolar septal widening caused by neoplastic lymphocytes, which were positive for CD20 and infiltrated in the alveolar capillaries. The patient was diagnosed with IVLBCL and underwent chemotherapy and autologous blood stem cell transplantation. The patient is still alive 5 years after diagnosis.IVLBCL is a rare cause of RHS and should be considered in differential diagnosis of RHS. An increased serum LDH concentration is another important clue. PMID:27015192

  20. Cyclophosphamide for Prevention of Graft-Versus-Host Disease After Allogeneic Peripheral Blood Stem Cell Transplantation in Patients With Hematological Malignancies

    Science.gov (United States)

    2015-08-04

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Myeloid Leukemia in Remission; Adult Erythroleukemia (M6a); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Adult Pure Erythroid Leukemia (M6b); Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Erythroleukemia (M6); Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Myeloid Leukemia in Remission; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Philadelphia Chromosome Negative Chronic Myelogenous Leukemia; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell

  1. The CXCR4 antagonist plerixafor enhances the effect of rituximab in diffuse large B-cell lymphoma cell lines

    DEFF Research Database (Denmark)

    Reinholdt, Linn; Laursen, Maria Bach; Schmitz, Alexander;

    2016-01-01

    strategies are needed. Antagonizing the CXCR4 receptor might be promising since the CXCR4-CXCL12 axis is implicated in several aspects of tumor pathogenesis as well as in protection from chemotherapeutic response. In Burkitt lymphoma, the CXCR4 antagonist plerixafor has already been shown to enhance the......BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is an aggressive disease with variable clinical outcome, accounting for at least 25-30 % of adult non-Hodgkin lymphomas. Approximately one third of DLBCL patients are not cured by the currently used treatment regimen, R-CHOP. Hence, new treatment...

  2. Increased Chromogranin A Cell Density in the Large Intestine of Patients with Irritable Bowel Syndrome after Receiving Dietary Guidance

    OpenAIRE

    Tarek Mazzawi; Doris Gundersen; Trygve Hausken; Magdy El-Salhy

    2015-01-01

    The large intestine contains five types of endocrine cells that regulate its functions by sensing its luminal contents and releasing specific hormones. Chromogranin A (CgA) is a common marker for the gastrointestinal endocrine cells, and it is abnormal in irritable bowel syndrome (IBS) patients. Most IBS patients relate their symptoms to certain food elements. The present study investigated the effect of dietary guidance on the total endocrine cells of the large intestine as detected by CgA i...

  3. Tacrolimus and Mycophenolate Mofetil With or Without Sirolimus in Preventing Acute Graft-Versus-Host Disease in Patients Who Are Undergoing Donor Stem Cell Transplant for Hematologic Cancer

    Science.gov (United States)

    2015-10-14

    II Grade 3 Non-Contiguous Follicular Lymphoma; Stage II Non-Contiguous Mantle Cell Lymphoma; Stage II Small Lymphocytic Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Burkitt Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Recurrent Childhood Hodgkin Lymphoma; Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Secondary Myelodysplastic Syndrome; Stage I Adult Burkitt Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Mixed Cell Lymphoma; Stage I Adult Immunoblastic Lymphoma; Stage I Adult Lymphoblastic Lymphoma; Stage I Childhood Anaplastic Large Cell Lymphoma; Stage I Childhood Large Cell Lymphoma; Stage I Childhood Lymphoblastic Lymphoma; Stage I Childhood Burkitt Lymphoma; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Grade 3 Follicular Lymphoma; Stage I Mantle Cell Lymphoma; Stage I Marginal Zone Lymphoma; Stage I Small Lymphocytic Lymphoma; Stage II Childhood Anaplastic Large Cell Lymphoma; Stage II Childhood Lymphoblastic Lymphoma; Stage II Childhood Burkitt Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell

  4. Intravascular large B-cell lymphoma of the kidney: A case report

    Directory of Open Access Journals (Sweden)

    Jia Nan

    2011-09-01

    Full Text Available Abstract We report a 41-year-old Chinese woman with intravascular large B-cell lymphoma diagnosed by percutaneous renal biopsy. The patient was admitted to Nanfang Hospital of Southern Medical University, Guangzhou, China with complaints of high spiking fever for a month and bilateral lower limb fatigue with difficulty ambulating for the past 5 months. She had renal dysfunction with a total urinary protein of 5.61 g/dL (56.1 g/L, serum albumin of 2.89 g/dL (28.9 g/L, urea nitrogen of 2.24 mg/dL (1.6 mmol/L, and serum creatinine of 0.54 mg/dL (48 μmol/L. Bone marrow biopsy revealed myeloproliferative disorder without abnormal myeloid or lymphocytic proliferation. Positron Emission Tomography-Computed Tomography (PET-CT showed marked bilateral swelling and enlargement of the renal parenchyma with splenic enlargement and involvement of multiple vertebrae. Percutaneous renal biopsy showed island-like accumulations of medium to large lymphoid cells in many areas of the interstitium, with round vesicular nuclei containing distinct basophilic nucleoli. Immunohistochemical analysis together with other supportive investigation confirmed the diagnosis of intravascular large B-cell lymphoma. Ten days later, she was started on chemotherapy with CHOP (cyclophosphamide, doxorubicin, leurocristime and prednisone for a week. Palliative radiotherapy DT 40Gy/20F with other supportive treatment was provided for metastatic foci in the medullary cavity of the sternum, T1-T7. The patient regained muscle strength in both lower limbs and was able to walk again after three weeks. The patient was discharged after hepatic and renal function and proteinuria values had returned to normal. Follow-up data shows the patient to be alive nine months after discharge.

  5. Technology for the large-scale production of multi-crystalline silicon solar cells and modules

    International Nuclear Information System (INIS)

    In cooperation with Shell Solar Energy (formerly R and S Renewable Energy Systems) and the Research Institute for Materials of the Catholic University Nijmegen the Netherlands Energy Research Foundation (ECN) plans to develop a competitive technology for the large-scale manufacturing of solar cells and solar modules on the basis of multi-crystalline silicon. The project will be carried out within the framework of the Economy, Ecology and Technology (EET) program of the Dutch ministry of Economic Affairs and the Dutch ministry of Education, Culture and Sciences. The aim of the EET-project is to reduce the costs of a solar module by 50% by means of increasing the conversion efficiency as well as the development of cheap processes for large-scale production

  6. Numb Chin Syndrome as First Symptom of Diffuse Large B-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Mario Carbone

    2014-01-01

    Full Text Available Numb chin syndrome is a rare sensory neuropathy of the mental nerve characterized by numbness, hypoesthesia, paraesthesia, and very rarely pain. Dental causes, especially iatrogenic ones, maxillofacial trauma, or malignant neoplasm are etiologic factors for this rare syndrome. Many malignant and metastatic neoplasms are causing this syndrome, like primary osteosarcoma, squamous cell carcinoma, and mandibular metastasis of primary carcinoma of breast, lung, thyroid, kidney, prostate, and nasopharynx. Haematological malignancies like acute lymphocytic leukaemia, Hodgkin and non-Hodgkin lymphoma, and myeloma can cause this neuropathy. The authors report a case of a 71-year-old woman in which the numb chin syndrome was the first symptom of the diffuse large B-cell lymphoma, which caused infiltration and reabsorption of the alveolar ridge and lower mandibular cortex. A biopsy of the mass was performed on fragments of tissue collected from the mandibular periosteum, medullary and cortical mandibular bone, and inferior alveolar nerve.

  7. Generation of Large Numbers of Antigen-Expressing Human Dendritic Cells Using CD14-ML Technology

    Science.gov (United States)

    Imamura, Yuya; Haruta, Miwa; Tomita, Yusuke; Matsumura, Keiko; Ikeda, Tokunori; Yuno, Akira; Hirayama, Masatoshi; Nakayama, Hideki; Mizuta, Hiroshi; Nishimura, Yasuharu; Senju, Satoru

    2016-01-01

    We previously reported a method to expand human monocytes through lentivirus-mediated introduction of cMYC and BMI1, and we named the monocyte-derived proliferating cells, CD14-ML. CD14-ML differentiated into functional DC (CD14-ML-DC) upon addition of IL-4, resulting in the generation of a large number of DC. One drawback of this method was the extensive donor-dependent variation in proliferation efficiency. In the current study, we found that introduction of BCL2 or LYL1 along with cMYC and BMI1 was beneficial. Using the improved method, we obtained CD14-ML from all samples, regardless of whether the donors were healthy individuals or cancer patients. In vitro stimulation of peripheral blood T cells with CD14-ML-DC that were loaded with cancer antigen-derived peptides led to the establishment of CD4+ and CD8+ T cell lines that recognized the peptides. Since CD14-ML was propagated for more than 1 month, we could readily conduct genetic modification experiments. To generate CD14-ML-DC that expressed antigenic proteins, we introduced lentiviral antigen-expression vectors and subjected the cells to 2 weeks of culture for drug-selection and expansion. The resulting antigen-expressing CD14-ML-DC successfully induced CD8+ T cell lines that were reactive to CMVpp65 or MART1/MelanA, suggesting an application in vaccination therapy. Thus, this improved method enables the generation of a sufficient number of DC for vaccination therapy from a small amount of peripheral blood from cancer patients. Information on T cell epitopes is not necessary in vaccination with cancer antigen-expressing CD14-ML-DC; therefore, all patients, irrespective of HLA type, will benefit from anti-cancer therapy based on this technology. PMID:27050553

  8. Progression after spontaneous regression in lung large cell neuroendocrine carcinoma: Report of a curative resection

    OpenAIRE

    Tomizawa, Kenji; Suda, Kenichi; Takemoto, Toshiki; Iwasaki, Takuya; Sakaguchi, Masahiro; Kuwano, Hiroyuki; Mitsudomi, Tetsuya

    2015-01-01

    We present the first reported case of lung large cell neuroendocrine carcinoma (LCNEC) with spontaneous regression followed by progression. An 85-year-old woman presented with a 2.8-cm nodule in the right upper lung lobe on chest computed tomography. After four months, the tumor decreased to 1.8 cm and remained unchanged in size for the next three months, but it grew to 8.6 cm and invaded the mediastinal fat tissue after approximately one year. Ultrasound echo-guided percutaneous biopsy revea...

  9. Diffuse large B cell lymphoma presenting as a peri-anal abscess.

    Science.gov (United States)

    Jayasekera, Hasanga; Gorissen, Kym; Francis, Leo; Chow, Carina

    2014-01-01

    A non-healing peri-anal abscess can be difficult to manage and is often attributed to chronic disease. This case documents a male in his seventh decade who presented with multiple peri-anal collections. The abscess cavity had caused necrosis of the internal sphincter muscles resulting in faecal incontinence. Biopsies were conclusive for diffuse large B-cell lymphoma. A de-functioning colostomy was performed and the patient was initiated on CHOP-R chemotherapy. Anal lymphoma masquerading as a peri-anal abscess is rare. A high degree of suspicion must be maintained for an anal abscess which does not resolve with conservative management. PMID:24898408

  10. Diffuse large B cell lymphoma presenting as a peri-anal abscess

    OpenAIRE

    Jayasekera, Hasanga; Gorissen, Kym; Francis, Leo; Chow, Carina

    2014-01-01

    A non-healing peri-anal abscess can be difficult to manage and is often attributed to chronic disease. This case documents a male in his seventh decade who presented with multiple peri-anal collections. The abscess cavity had caused necrosis of the internal sphincter muscles resulting in faecal incontinence. Biopsies were conclusive for diffuse large B-cell lymphoma. A de-functioning colostomy was performed and the patient was initiated on CHOP-R chemotherapy. Anal lymphoma masquerading as a ...

  11. Primary diffuse large B-cell non-Hodgkin lymphoma of the cranial vault

    Directory of Open Access Journals (Sweden)

    Shantanu Ghosh

    2014-09-01

    Full Text Available Primary non-Hodgkin lymphoma of the cranial vault with extra and intracranial extension in a nonimmunocompromised patient is extremely uncommon. Until date, only limited number of such cases has been reported in the literature and none was the lesion located as a diffuse swelling in the forehead. Imaging of the present case showed in a homogenous contrast enhancement mass involving the scalp of bifrontal supraorbital compartment and intracranial extra axial extension through the frontal bone with extension to the right orbit and right ethmoidal sinus. The intracranial mass was excised along with involved dura. Histopathology of the mass showed diffuse large B-cell non-Hodgkin lymphoma.

  12. Graphene oxide hole transport layers for large area, high efficiency organic solar cells

    OpenAIRE

    Smith, CTG; Rhodes, RW; Beliatis, MJ; Jayawardena, KDGI; Rozanski, LJ; Mills, CA; Silva, SRP

    2014-01-01

    Graphene oxide (GO) is becoming increasingly popular for organic electronic applications. We present large active area (0.64 cm^2), solution processable, poly[[9-(1-octylnonyl)-9H-carbazole-2,7-diyl]-2,5-thiophenediyl-2,1,3-benzothiadiazole-4,7-diyl-2,5-thiophenediyl]:[6,6]-Phenyl C71 butyric acid methyl ester (PCDTBT:PC70BM) organic photovoltaic (OPV) solar cells, incorporating GO hole transport layers (HTL). The power conversion efficiency (PCE) of ~5% is the highest reported for OPV using ...

  13. Diffuse large B-cell lymphoma of the kidney: A rare neoplasm

    Directory of Open Access Journals (Sweden)

    Ram Narayan Das

    2013-01-01

    Full Text Available Primary renal lymphoma is a rare neoplasm, but it should be kept in mind in the differential diagnosis of renal neoplasms. A middle aged man presented with symptoms of weight loss, anorexia and fullness of the abdomen after meals. On clinical and radiological examination, a renal mass was revealed and operated upon. A diagnosis of primary high grade renal lymphoma was made on histopathological examination and immunohistochemically it was further classified as diffuse large B-cell lymphoma. Unfortunately, the patient died after 5 months of diagnosis in spite of three cycles of chemotherapy following surgery. The pathological details of rare tumor are presented here.

  14. Wire-Cell Tomographic Event Reconstruction for large LArTPCs

    Science.gov (United States)

    Qian, Xin; Viren, Brett; Zhang, Chao; Wire-Cell Team

    2016-03-01

    Event reconstruction is one of the most challenging tasks in analyzing the data from current and future large liquid argon time projection chambers (LArTPCs). The performance of the event reconstruction holds the key to many potential future discoveries with the LArTPC technology including i) searching for new CP violation in the leptonic sector, ii) determining the neutrino mass hierarchy, and iii) searching for additional light (sterile) neutrino species. In this talk, we introduce a new reconstruction method: Wire-Cell. The principle of Wire-Cell strictly follows the principle of LArTPC, that is, the same amount of ionization electrons are observed by all the wire-planes. Using both time and charge information, 3D image of the event topologies are firstly obtained. Further reconstruction steps including the clustering, tracking, and particle identifications (PID) are then directly applied to the 3D image. The principle, current status, and future development plan of Wire-Cell will be described. The results of Wire-Cell event reconstruction will be shown with an innovative web-based ``BEE'' 3D event display. This work is supported by U.S. Department of Energy, Office of Science, Office of High Energy Physics and Early Career Research program under Contract Number DE-SC0012704.

  15. Investigation of Low-Cost Surface Processing Techniques for Large-Size Multicrystalline Silicon Solar Cells

    Directory of Open Access Journals (Sweden)

    Shun-Hsyung Chang

    2010-01-01

    Full Text Available The subject of the present work is to develop a simple and effective method of enhancing conversion efficiency in large-size solar cells using multicrystalline silicon (mc-Si wafer. In this work, industrial-type mc-Si solar cells with area of 125×125 mm2 were acid etched to produce simultaneously POCl3 emitters and silicon nitride deposition by plasma-enhanced chemical vapor deposited (PECVD. The study of surface morphology and reflectivity of different mc-Si etched surfaces has also been discussed in this research. Using our optimal acid etching solution ratio, we are able to fabricate mc-Si solar cells of 16.34% conversion efficiency with double layers silicon nitride (Si3N4 coating. From our experiment, we find that depositing double layers silicon nitride coating on mc-Si solar cells can get the optimal performance parameters. Open circuit (Voc is 616 mV, short circuit current (Jsc is 34.1 mA/cm2, and minority carrier diffusion length is 474.16 μm. The isotropic texturing and silicon nitride layers coating approach contribute to lowering cost and achieving high efficiency in mass production.

  16. Pathophysiological significance and therapeutic targeting of germinal center kinase in diffuse large B-cell lymphoma.

    Science.gov (United States)

    Matthews, Julie Marie; Bhatt, Shruti; Patricelli, Matthew P; Nomanbhoy, Tyzoon K; Jiang, Xiaoyu; Natkunam, Yasodha; Gentles, Andrew J; Martinez, Ezequiel; Zhu, Daxing; Chapman, Jennifer Rose; Cortizas, Elena; Shyam, Ragini; Chinichian, Shideh; Advani, Ranjana; Tan, Li; Zhang, Jianming; Choi, Hwan Geun; Tibshirani, Robert; Buhrlage, Sara J; Gratzinger, Dita; Verdun, Ramiro; Gray, Nathanael S; Lossos, Izidore S

    2016-07-14

    Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma, yet 40% to 50% of patients will eventually succumb to their disease, demonstrating a pressing need for novel therapeutic options. Gene expression profiling has identified messenger RNAs that lead to transformation, but critical events transforming cells are normally executed by kinases. Therefore, we hypothesized that previously unrecognized kinases may contribute to DLBCL pathogenesis. We performed the first comprehensive analysis of global kinase activity in DLBCL, to identify novel therapeutic targets, and discovered that germinal center kinase (GCK) was extensively activated. GCK RNA interference and small molecule inhibition induced cell-cycle arrest and apoptosis in DLBCL cell lines and primary tumors in vitro and decreased the tumor growth rate in vivo, resulting in a significantly extended lifespan of mice bearing DLBCL xenografts. GCK expression was also linked to adverse clinical outcome in a cohort of 151 primary DLBCL patients. These studies demonstrate, for the first time, that GCK is a molecular therapeutic target in DLBCL tumors and that inhibiting GCK may significantly extend DLBCL patient survival. Because the majority of DLBCL tumors (∼80%) exhibit activation of GCK, this therapy may be applicable to most patients. PMID:27151888

  17. 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.

  18. Selenium compounds induce ROS in human high-metastatic large cell lung cancer cell line L9981

    Directory of Open Access Journals (Sweden)

    Chengfei LIU

    2008-06-01

    Full Text Available Background and objective It has been proved that methylseleninic acid (MSA is a kind of artificially developed selenium compound, which appeared to be the best candidate for cancer prevention and therapy. Reduced glutathione is not only critical to MSA metabolism, but also is a kind of protective antioxidant which could remove the oxygen free radical promptly and maintain the intracellular redox status stable. The aim of this study is to explore the anticancer effects of ROS induced by MSA and the molecular mechanisms of MSA on induction of ROS. Methods We confirmed that MSA and selenite have the anticancer effect in the human high-metastatic large cell lung cancer cell line L9981 by growth inhibition detection, we detect the ROS induced by MSA and selenite in L9981 by fluorescence microscopy, and use flow cytometry to quantitate the ROS induced by NAC together with selenium compounds. Results ①MSA 2.5 μM and 5.0 μM selenite could inhibit the L9981 growth, Increasing the concentration resulted in a more pronounced effect. ②MSA and selenite could induce ROS in L9981. ③incubated NAC with selenite could significantly inhibit the ROS but increase the ROS treated by NAC with MSA. Conclusions ①MSA and selenite had anti-L9981 effect. ②Oxidative stress reaction may participate in the induction of apoptosis by MSA and selenite in lung cancer cell line L9981.

  19. Plitidepsin (Aplidin) is a potent inhibitor of diffuse large cell and Burkitt lymphoma and is synergistic with rituximab

    OpenAIRE

    Barboza, Nora M.; Medina, Daniel J; Budak-Alpdogan, Tulin; Aracil, Miguel; Jimeno, José M; Bertino, Joseph R.; Banerjee, Debabrata

    2012-01-01

    Plitidepsin (Aplidin), an antitumor agent of marine origin, presently is undergoing phase II/III clinical trials, and has shown promise for the treatment of lymphoma. Here, we describe the antitumor effects of plitidepsin alone and in combination with rituximab and investigated the effects of each drug and the combination on the cell cycle and mechanism of cell death. Several Diffuse Large Cell Lymphoma (DLCL) lines and Burkitt cell lines were tested for sensitivity to plitidepsin and rituxim...

  20. Inhibition of COP9-signalosome (CSN) deneddylating activity and tumor growth of diffuse large B-cell lymphomas by doxycycline

    OpenAIRE

    Pulvino, Mary; Chen, Luojing; Oleksyn, David; Li, Jing; Compitello, George; Rossi, Randy; Spence, Stephen; Balakrishnan, Vijaya; Jordan, Craig; Poligone, Brian; Casulo, Carla; Burack, Richard; Shapiro, Joel L.; Bernstein, Steven; Friedberg, Jonathan W.

    2015-01-01

    In searching for small-molecule compounds that inhibit proliferation and survival of diffuse large B-cell lymphoma (DLBCL) cells and may, therefore, be exploited as potential therapeutic agents for this disease, we identified the commonly used and well-tolerated antibiotic doxycycline as a strong candidate. Here, we demonstrate that doxycycline inhibits the growth of DLBCL cells both in vitro and in mouse xenograft models. In addition, we show that doxycycline accumulates in DLBCL cells to hi...

  1. The Role of Large Animal Studies in Cardiac Regenerative Therapy Concise Review of Translational Stem Cell Research

    OpenAIRE

    Kwon, Sung Uk; Yeung, Alan C.; Ikeno, Fumiaki

    2013-01-01

    Animal models have long been developed for cardiovascular research. These animal models have been helpful in understanding disease, discovering potential therapeutics, and predicting efficacy. Despite many efforts, however, translational study has been underestimated. Recently, investigations have identified stem cell treatment as a potentially promising cell therapy for regenerative medicine, largely because of the stem cell's ability to differentiate into many functional cell types. Stem ce...

  2. Large-scale RNA interference screening in mammalian cells identifies novel regulators of mutant huntingtin aggregation.

    Directory of Open Access Journals (Sweden)

    Tomoyuki Yamanaka

    Full Text Available In polyglutamine (polyQ diseases including Huntington's disease (HD, mutant proteins containing expanded polyQ stretch form aggregates in neurons. Genetic or RNAi screenings in yeast, C. elegans or Drosophila have identified multiple genes modifying polyQ aggregation, a few of which are confirmed effective in mammals. However, the overall molecular mechanism underlying polyQ protein aggregation in mammalian cells still remains obscure. We here perform RNAi screening in mouse neuro2a cells to identify mammalian modifiers for aggregation of mutant huntingtin, a causative protein of HD. By systematic cell transfection and automated cell image analysis, we screen ∼ 12000 shRNA clones and identify 111 shRNAs that either suppress or enhance mutant huntingtin aggregation, without altering its gene expression. Classification of the shRNA-targets suggests that genes with various cellular functions such as gene transcription and protein phosphorylation are involved in modifying the aggregation. Subsequent analysis suggests that, in addition to the aggregation-modifiers sensitive to proteasome inhibition, some of them, such as a transcription factor Tcf20, and kinases Csnk1d and Pik3c2a, are insensitive to it. As for Tcf20, which contains polyQ stretches at N-terminus, its binding to mutant huntingtin aggregates is observed in neuro2a cells and in HD model mouse neurons. Notably, except Pik3c2a, the rest of the modifiers identified here are novel. Thus, our first large-scale RNAi screening in mammalian system identifies previously undescribed genetic players that regulate mutant huntingtin aggregation by several, possibly mammalian-specific mechanisms.

  3. Clinical Analysis of 22 Cases of Pulmonary Large Cell Neuroendocrine Cancer

    Directory of Open Access Journals (Sweden)

    Zhe QIAN

    2016-02-01

    Full Text Available Background and objective Pulmonary large cell neuroendocrine carcinoma (LCNEC is a rare primary malignant tumor. Due to poor understanding of its biologic behaviors, pathological features, image manifestations and clinical effects, clinical study is urgent. Analysis of clinical data of pulmonary LCNEC, in order to improve the clinical diagnosis and treatment. Methods Retrospective analysis of 22 pulmonary LCNEC cases of clinical features, diagnosis, treatments and prognosis. Results Pulmonary large cell neuroendocrine carcinoma occurs in older men with heavy smoking history., clinical symptoms are cough, sputum, hemoptysis, and chest pain. Computed tomography (CT features are peripheral mass mainly, accompanied by heterogeneous density and necrosis. Immunohistochemical neuroendocrine differentiation markers Syn, CgA and CD56 positive expression rates were: 72.7%, 68.2% and 68.2%, respectively. 17 patients underwent surgical treatment, 10 patients received adjuvant therapy, 5 underwent palliative chemotherapy. Univariate analysis indicated that smoking index (P=0.029, lymph node metastasis (P=0.034, tumor-node-metastasis (TNM stage (P=0.005, treatment (P=0.047, postoperative chemotherapy (P=0.014 are prognostic factors. Multivariate analysis showed that lymph node metastasis (P=0.045 and postoperative chemotherapy (P=0.024 are prognostic factors. Conclusion Pulmonary LCNEC is lack of specific clinical symptoms, and its pathological diagnosis depends on postoperative specimens, poor efficacy of various treatments is its current situation. Lymph node metastasis and postoperative chemotherapy are important prognostic factors.

  4. The role of printing techniques for large-area dye sensitized solar cells

    International Nuclear Information System (INIS)

    The versatility of printing technologies and their intrinsic ability to outperform other techniques in large-area deposition gives scope to revolutionize the photovoltaic (PV) manufacturing field. Printing methods are commonly used in conventional silicon-based PVs to cover part of the production process. Screen printing techniques, for example, are applied to deposit electrical contacts on the silicon wafer. However, it is with the advent of third generation PVs that printing/coating techniques have been extensively used in almost all of the manufacturing processes. Among all the third generation PVs, dye sensitized solar cell (DSSC) technology has been developed up to commercialization levels. DSSCs and modules can be fabricated by adopting all of the main printing techniques on both rigid and flexible substrates. This allows an easy tuning of cell/module characteristics to the desired application. Transparency, colour, shape, layout and other DSSC’s features can be easily varied by changing the printing parameters and paste/ink formulations used in the printing process. This review focuses on large-area printing/coating technologies for the fabrication of DSSCs devices. The most used and promising techniques are presented underlining the process parameters and applications. (paper)

  5. The role of printing techniques for large-area dye sensitized solar cells

    Science.gov (United States)

    Mariani, Paolo; Vesce, Luigi; Di Carlo, Aldo

    2015-10-01

    The versatility of printing technologies and their intrinsic ability to outperform other techniques in large-area deposition gives scope to revolutionize the photovoltaic (PV) manufacturing field. Printing methods are commonly used in conventional silicon-based PVs to cover part of the production process. Screen printing techniques, for example, are applied to deposit electrical contacts on the silicon wafer. However, it is with the advent of third generation PVs that printing/coating techniques have been extensively used in almost all of the manufacturing processes. Among all the third generation PVs, dye sensitized solar cell (DSSC) technology has been developed up to commercialization levels. DSSCs and modules can be fabricated by adopting all of the main printing techniques on both rigid and flexible substrates. This allows an easy tuning of cell/module characteristics to the desired application. Transparency, colour, shape, layout and other DSSC’s features can be easily varied by changing the printing parameters and paste/ink formulations used in the printing process. This review focuses on large-area printing/coating technologies for the fabrication of DSSCs devices. The most used and promising techniques are presented underlining the process parameters and applications.

  6. Cutaneous diffuse large B-cell lymphoma of the leg associated with chronic lymphedema.

    Science.gov (United States)

    González-Vela, M Carmen; González-López, Marcos A; Val-Bernal, J Fernando; Fernández-Llaca, Héctor

    2008-02-01

    Development of malignant tumors is a rare but well known complication in chronic lymphedema (CL). We report herein a cutaneous diffuse large B-cell lymphoma of the leg associated with CL. An 89-year-old man presented with multiple cutaneous lesions on his right limb that showed a CL. Dermatological examination disclosed multiple violaceous, firm, slightly infiltrated nodules on the anterior aspect of the leg and the dorsum and sole of the foot. A biopsy of one nodule of the leg disclosed a diffuse large B-cell lymphoma, type of the legs. There was no evidence of lymphadenopathy on computed tomography (CT) scans of the chest, abdomen, and pelvis. A bone marrow aspiration and biopsy showed normal results. The patient was treated with local radiotherapy at a dose of 40 Gy, obtaining a highly significant, almost complete, clinical remission. A literature search identified 11 additional cases of primary cutaneous lymphoma associated with CL. An inadequate lymphatic drainage may make the lymphedematous region an immunologically vulnerable area, predisposing to neoplasia. PMID:18211492

  7. Heart of Lymphoma: Primary Mediastinal Large B-Cell Lymphoma with Endomyocardial Involvement

    Directory of Open Access Journals (Sweden)

    Elisa Rogowitz

    2013-01-01

    Full Text Available Primary mediastinal B-cell lymphoma (PMBCL is an uncommon aggressive subset of diffuse large B-cell lymphomas. Although PMBCL frequently spreads locally from the thymus into the pleura or pericardium, it rarely invades directly through the heart. Herein, we report a case of a young Mexican female diagnosed with PMBCL with clear infiltration of lymphoma through the cardiac wall and into the right atrium and tricuspid valve leading to tricuspid regurgitation. This was demonstrated by cardiac MRI and transthoracic echocardiogram. In addition, cardiac MRI and CT scan of the chest revealed the large mediastinal mass completely surrounding and eroding into the superior vena cava (SVC wall causing a collar of stokes. The cardiac and SVC infiltration created a significant therapeutic challenge as lymphomas are very responsive to chemotherapy, and treatment could potentially lead to vascular wall rupture and hemorrhage. Despite the lack of conclusive data on chemotherapy-induced hemodynamic compromise in such scenarios, her progressive severe SVC syndrome and respiratory distress necessitated urgent intervention. In addition to the unique presentation of this rare lymphoma, our case report highlights the safety of R-CHOP treatment.

  8. 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

  9. 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

  10. Endoscopic submucosal tunnel dissection for large superficial esophageal squamous cell neoplasms.

    Science.gov (United States)

    Zhai, Ya-Qi; Li, Hui-Kai; Linghu, En-Qiang

    2016-01-01

    Endoscopic submucosal dissection (ESD) is a well-established treatment for superficial esophageal squamous cell neoplasms (SESCNs) with no risk of lymphatic metastasis. However, for large SESCNs, especially when exceeding two-thirds of the esophageal circumference, conventional ESD is time-consuming and has an increased risk of adverse events. Based on the submucosal tunnel conception, endoscopic submucosal tunnel dissection (ESTD) was first introduced by us to remove large SESCNs, with excellent results. Studies from different centers also reported favorable results. Compared with conventional ESD, ESTD has a more rapid dissection speed and R0 resection rate. Currently in China, ESTD for large SESCNs is an important part of the digestive endoscopic tunnel technique, as is peroral endoscopic myotomy for achalasia and submucosal tunnel endoscopic resection for submucosal tumors of the muscularis propria. However, not all patients with SESCNs are candidates for ESTD, and postoperative esophageal strictures should also be taken into consideration, especially for lesions with a circumference greater than three-quarters. In this article, we describe our experience, review the literature of ESTD, and provide detailed information on indications, standard procedures, outcomes, and complications of ESTD. PMID:26755889

  11. Realization of high performance silicon nanowire based solar cells with large size

    International Nuclear Information System (INIS)

    We report the realization of high performance silicon nanowire (SiNW) based solar cells with a conversion efficiency of 17.11% and a large size of 125 × 125 mm2. The key factor for success lies in an efficient approach of dielectric passivation to greatly enhance the electrical properties while keeping the advantage of excellent light trapping of the SiNW structure. The suppression of carrier recombination has been demonstrated through the combination of the SiO2/SiNx stack, which exhibits a good passivation effect on heavily doped SiNWs via reducing both the Shockley–Read–Hall recombination and near surface Auger recombination. We have examined in detail the effects of different passivations and SiNW lengths on the effective minority carrier lifetime, reflectance and carrier recombination characteristics, as well as cell performance. The proposed passivation techniques can be easily adapted to conventional industrial manufacturing processes, providing a potential prospect of SiNW based solar cells in mass production. (paper)

  12. Fludarabine and Total-Body Irradiation Followed By Donor Stem Cell Transplant and Cyclosporine and Mycophenolate Mofetil in Treating HIV-Positive Patients With or Without Cancer

    Science.gov (United States)

    2015-08-28

    Accelerated Phase Chronic Myelogenous Leukemia; Acute Undifferentiated Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Grade III Lymphomatoid Granulomatosis; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Aggressive NK-cell Leukemia; AIDS-related Diffuse Large Cell Lymphoma; AIDS-related Diffuse Mixed Cell Lymphoma; AIDS-related Diffuse Small Cleaved Cell Lymphoma; AIDS-related Immunoblastic Large Cell Lymphoma; AIDS-related Lymphoblastic Lymphoma; AIDS-related Peripheral/Systemic Lymphoma; AIDS-related Primary CNS Lymphoma; AIDS-related Small Noncleaved Cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Grade III Lymphomatoid Granulomatosis; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Contiguous Stage II Adult Burkitt Lymphoma; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Contiguous Stage II Adult Lymphoblastic Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2

  13. Diffuse large B-cell lymphoma: sub-classification by massive parallel quantitative RT-PCR.

    Science.gov (United States)

    Xue, Xuemin; Zeng, Naiyan; Gao, Zifen; Du, Ming-Qing

    2015-01-01

    Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous entity with remarkably variable clinical outcome. Gene expression profiling (GEP) classifies DLBCL into activated B-cell like (ABC), germinal center B-cell like (GCB), and Type-III subtypes, with ABC-DLBCL characterized by a poor prognosis and constitutive NF-κB activation. A major challenge for the application of this cell of origin (COO) classification in routine clinical practice is to establish a robust clinical assay amenable to routine formalin-fixed paraffin-embedded (FFPE) diagnostic biopsies. In this study, we investigated the possibility of COO-classification using FFPE tissue RNA samples by massive parallel quantitative reverse transcription PCR (qRT-PCR). We established a protocol for parallel qRT-PCR using FFPE RNA samples with the Fluidigm BioMark HD system, and quantified the expression of the COO classifier genes and the NF-κB targeted-genes that characterize ABC-DLBCL in 143 cases of DLBCL. We also trained and validated a series of basic machine-learning classifiers and their derived meta classifiers, and identified SimpleLogistic as the top classifier that gave excellent performance across various GEP data sets derived from fresh-frozen or FFPE tissues by different microarray platforms. Finally, we applied SimpleLogistic to our data set generated by qRT-PCR, and the ABC and GCB-DLBCL assigned showed the respective characteristics in their clinical outcome and NF-κB target gene expression. The methodology established in this study provides a robust approach for DLBCL sub-classification using routine FFPE diagnostic biopsies in a routine clinical setting. PMID:25418578

  14. 77例T细胞非霍奇金淋巴瘤的临床病理特点和免疫表型分析%The clinicopathologic features and immunophenotypes of T-cell non-Hodgkin's lymphoma: an analysis of 77 cases

    Institute of Scientific and Technical Information of China (English)

    赵伟; 陈陆俊; 田波; 谈炎; 鲁常青

    2012-01-01

    Objective To study the clinicopathologic features and immunophenotypes of T-cell non-Hodgkin's lymphoma. Methods Seventy-seven of T-cell non-Hodgkin s lymphomas were studied by light microscopy and immunohistochemistry. All cases were reclassified according to the new WHO classification of lymphomas. Results Of 77 T-cell non-Hodgkin's lymphomas,32(41. 6%) cases were extranodal NK/T cell lymphomas of nasal type,20(26. 0%) cases were nonspecific peripheral T cell lymphomas, 11 (14. 3%) cases were anaplastic large cell lymphomas and 9(11.7%) cases were precursor T lymphoblastic lymphomas. Conclusion Among T-cell non-Hodgkin's lymphomas, extranodal NK/T cell lymphoma of nasal type is the most common subtype. The other main subtypes conclude nonspecific peripheral T cell lymphomas, anaplastic large cell lymphomas and precursor T lymphoblastic lymphomas. The patients with extranodal NK/T cell lymphomas of nasal type have poor prognosis, while those with anaplastic large cell lymphomas have favorable prognosis.%目的 探讨T细胞非霍奇金淋巴瘤的临床病理特点和免疫表型.方法 对77例T细胞非霍奇金淋巴瘤进行苏木素和伊红染色(HE)和免疫组织化学检查,按WHO 2008年《造血和淋巴 组织肿瘤的病理学和遗传学》标准进行分类.结果 77例T细胞非霍奇金淋巴瘤中,鼻型结外NK/T细胞淋巴瘤32例(41.6%),非特异性外周T细胞淋巴瘤20例(26.0%),间变性大细胞淋巴瘤11例(14.3%),前驱T淋巴细胞淋巴瘤9例(11.7%).结论 T细胞非霍奇金淋巴瘤中,最常发生的亚型是鼻型结外NK/T细胞淋巴瘤,其次为非特异性外周T细胞淋巴瘤、间变性大细胞淋巴瘤和前驱T淋巴细胞淋巴瘤.其中,鼻型结外NK/T细胞淋巴瘤预后较差,而间变性大细胞淋巴瘤预后相对 较好.

  15. 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

  16. 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

  17. 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

  18. Thymic large cell neuroendocrine carcinoma: report of a resected case - a case report

    Directory of Open Access Journals (Sweden)

    Jiang Shi-Xu

    2010-11-01

    Full Text Available Abstract Thymic large cell neuroendocrine carcinomas (LCNECs are very rare. We here describe a case in which the tumor could be completely resected. A 55-year-old male was admitted to our hospital for treatment of an anterior mediastinal tumor found at a regular health check-up. The patient underwent an extended thymectomy of an invasive thymoma of Masaoka's stage II that had been suspected preoperatively. The tumor was located in the right lobe of the thymus and was completely resected. Final pathological diagnosis of the surgical specimen was thymic LCNEC. The patient underwent adjuvant chemotherapy with irinotecan and cisplatin in accordance with the diagnosis of a lung LCNEC, and is alive without recurrence or metastasis 16 months after surgery.

  19. Progression after spontaneous regression in lung large cell neuroendocrine carcinoma: Report of a curative resection.

    Science.gov (United States)

    Tomizawa, Kenji; Suda, Kenichi; Takemoto, Toshiki; Iwasaki, Takuya; Sakaguchi, Masahiro; Kuwano, Hiroyuki; Mitsudomi, Tetsuya

    2015-09-01

    We present the first reported case of lung large cell neuroendocrine carcinoma (LCNEC) with spontaneous regression followed by progression. An 85-year-old woman presented with a 2.8-cm nodule in the right upper lung lobe on chest computed tomography. After four months, the tumor decreased to 1.8 cm and remained unchanged in size for the next three months, but it grew to 8.6 cm and invaded the mediastinal fat tissue after approximately one year. Ultrasound echo-guided percutaneous biopsy revealed the tumor to be LCNEC. The patient underwent a right upper lobectomy with lymph node dissection. She had a good postoperative course with no complications. Physicians and surgeons should be aware that radiographic regression of a pulmonary nodule does not necessarily exclude the possibility of lung cancer. PMID:26443884

  20. SEOM clinical guidelines for the treatment of diffuse large B-cell lymphoma.

    Science.gov (United States)

    Gómez Codina, José; Sabín Domínguez, Pilar; Provencio Pulla, Mariano; Rueda Domínguez, Antonio; Isla Casado, Dolores

    2010-11-01

    Diffuse large B-cell non-Hodgkin's lymphoma (LDCGB) is one of the best examples of chemotherapy curable malignant diseases. This "Oncoguía SEOM" summarizes the basic directions of staging and recommended treatment options. The staging study should be thorough and includes clinical, laboratory, diagnostic imaging and nuclear medicine. Treatment depends on patient characteristics and comorbidity and on disease extension and prognostic factors. In localized cases, chemoimmunotherapy (CHOP-R) of short duration, followed by involved-field irradiation is the preferred option. In advanced stages, the association of CHOP-like chemotherapy and Rituximab has been a major breakthrough in terms of cure rate. It is important do not forget the supportive treatment in these patients. PMID:20974570

  1. Deregulation of COMMD1 Is Associated with Poor Prognosis in Diffuse Large B-cell Lymphoma

    DEFF Research Database (Denmark)

    Taskinen, M.; Louhimo, R.; Koivula, S.;

    2014-01-01

    Background: Despite improved survival for the patients with diffuse large B-cell lymphoma (DLBCL), the prognosis after relapse is poor. The aim was to identify molecular events that contribute to relapse and treatment resistance in DLBCL. Methods: We analysed 51 prospectively collected pretreatment...... associated with unfavourable survival. The 2p15 aberration harboured COMMD1 gene, whose expression had a significant adverse prognostic impact on survival. Immunohistochemical analysis of COMMD1 expression in two series confirmed the association of COMMD1 expression with poor prognosis. Conclusion: COMMD1 is...... a potential novel prognostic factor in DLBCLs. The results highlight the value of integrated comprehensive analysis to identify prognostic markers and genetic driver events not previously implicated in DLBCL....

  2. Large cystic renal cell carcinoma leading to diagnostic dilemma: a case report.

    Science.gov (United States)

    Amar, V; Vennapusa, B; Kumar, M Mahendra; Nagaraju, B; Srinivas, G; Bhargav, P R K

    2013-06-01

    Large cystic renal tumours can be confused with hepatic lesions even on crosssectional imaging. Careful clinical, sonographic and imaging analysis is needed for establishing correct diagnosis. We report a case of papillary cystic renal carcinoma in a 60 year old man, which was confused with amoebic liver abcess and was initially drained. Subsequent recurrence of symptoms prompted us to re-evaluate the case and repeat sonography confirmed the extrahepatic origin of mass based on simple observation that the liver and mass were moving separately on inspiration. Later guided aspiration from solid component of the mass confirmed the diagnosis as renal cell carcinoma. He was successfully treated with radical nephrectomy with uneventful post-operative recovery. PMID:24426529

  3. Low-Dose Total Body Irradiation and Donor Peripheral Blood Stem Cell Transplant Followed by Donor Lymphocyte Infusion in Treating Patients With Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, or Multiple Myeloma

    Science.gov (United States)

    2015-10-30

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage II Multiple Myeloma; Stage III Multiple Myeloma; Testicular Lymphoma; Waldenström Macroglobulinemia

  4. 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.

  5. Deciphering the therapeutic stem cell strategies of large and midsize pharmaceutical firms.

    Science.gov (United States)

    Vertès, Alain A

    2014-01-01

    The slow adoption of cytotherapeutics remains a vexing hurdle given clinical progress achieved to date with a variety of stem cell lineages. Big and midsize pharmaceutical companies as an asset class still delay large-scale investments in this arena until technological and market risks will have been further reduced. Nonetheless, a handful of stem cell strategic alliance and licensing transactions have already been implemented, indicating that progress is actively monitored, although most of these involve midsize firms. The greatest difficulty is, perhaps, that the regenerative medicine industry is currently only approaching the point of inflexion of the technology development S-curve, as many more clinical trials read out. A path to accelerating technology adoption is to focus on innovation outliers among healthcare actors. These can be identified by analyzing systemic factors (e.g., national science policies and industry fragmentation) and intrinsic factors (corporate culture, e.g., nimble decision-making structures; corporate finance, e.g., opportunity costs and ownership structure; and operations, e.g., portfolio management strategies, threats on existing businesses and patent expirations). Another path is to accelerate the full clinical translation and commercialization of an allogeneic cytotherapeutic product in any indication to demonstrate the disease-modifying potential of the new products for treatment and prophylaxis, ideally for a large unmet medical need such as dry age-related macular degeneration, or for an orphan disease such as biologics-refractory acute graft-versus-host disease. In times of decreased industry average research productivities, regenerative medicine products provide important prospects for creating new franchises with a market potential that could very well mirror that achieved with the technology of monoclonal antibodies. PMID:25159065

  6. Secondary infiltration of the central nervous system in patients with diffuse large B-cell lymphoma

    Directory of Open Access Journals (Sweden)

    Talita Maira Bueno da Silveira da Rocha

    2013-01-01

    Full Text Available OBJECTIVE: To investigate the incidence and risk factors of infiltration of the central nervous system after the initial treatment of diffuse large B-cell lymphoma in patients treated at Santa Casa de Misericórdia de São Paulo. METHODS: A total of 133 patients treated for diffuse large B-cell lymphoma from January 2001 to April 2008 were retrospectively analyzed in respect to the incidence and risk factors of secondary central nervous system involvement of lymphoma. Intrathecal prophylaxis was not a standard procedure for patients considered to be at risk. This analysis includes patients whether they received rituximab as first-line treatment or not. RESULTS: Nine of 133 (6.7% patients developed central nervous system disease after a mean observation time of 29 months. The median time to relapse or progression was 7.9 months after diagnosis and all but one patient died despite the treatment administered. Twenty-six (19.5% patients of this cohort received rituximab as first-line treatment and nine (7.1% received intrathecal chemoprophylaxis. Of the nine patients that relapsed, seven (77.7% had parenchymal central nervous system involvement; seven (77.7% had stage III or IV disease; one (11.1% had bone marrow involvement; two (22.2% had received intrathecal chemoprophylaxis; and 3 (33.3% had taken rituximab. In a multivariate analysis, the risk factors for this infiltration were being male, previous use of intrathecal chemotherapy and patients that were refractory to initial treatment. CONCLUSION: Central nervous system infiltration in this cohort is similar to that of previous reports in the literature. As this was a small cohort with a rare event, only three risk factors were important for this infiltration

  7. Long-term efficacy and safety of tocilizumab in giant cell arteritis and large vessel vasculitis

    Science.gov (United States)

    Evans, Jobie; Steel, Lauren; Borg, Frances; Dasgupta, Bhaskar

    2016-01-01

    Giant cell arteritis (GCA) is a chronic systemic vasculitis affecting large-sized and medium-sized vessels. Glucocorticoids are currently the mainstay of treatment for GCA and associated large vessel vasculitis (LVV) but are associated with frequent adverse events. Methotrexate has only demonstrated a modest benefit while anti-TNF biological agents (infliximab and etanercept) have been inefficacious. Elevated levels of interleukin-6 (IL-6), a proinflammatory cytokine, has been associated with GCA. Tocilizumab (TCZ), a humanised antihuman IL-6 receptor antibody, has been used successfully in several reports as a treatment for GCA and LVV. We report the potentially long-term successful use of TCZ in 8 cases of refractory LVV. All of our patients achieved a good clinical response to TCZ and C reactive protein reduced from an average of 70.3 to 2.5. In all cases, the glucocorticoid dose was reduced, from an average of 24.6 mg prednisolone prior to TCZ treatment to 4.7 mg, indicating that TCZ may enable a reduction in glucocorticoid-associated adverse events. However, regular TCZ administration was needed for disease control in most cases. TCZ was discontinued in one case due to the development of an empyema indicating the need for careful monitoring of infection when using this treatment. PMID:26819753

  8. Collisionless Reconnection in the Large Guide Field Regime: Gyrokinetic Versus Particle-in-Cell Simulations

    CERN Document Server

    TenBarge, J M; Karimabadi, H; Howes, G G; Dorland, W

    2013-01-01

    Results of the first validation of large guide field, $B_g / \\delta B_0 \\gg 1$, gyrokinetic simulations of magnetic reconnection at a fusion and solar corona relevant $\\beta_i = 0.01$ and solar wind relevant $\\beta_i = 1$ are presented, where $\\delta B_0$ is the reconnecting field. Particle-in-cell (PIC) simulations scan a wide range of guide magnetic field strength to test for convergence to the gyrokinetic limit. The gyrokinetic simulations display a high degree of morphological symmetry, to which the PIC simulations converge when $\\beta_i B_g / \\delta B_0 \\gtrsim 1$ and $B_g / \\delta B_0 \\gg 1$. In the regime of convergence, the reconnection rate, relative energy conversion, and overall magnitudes are found to match well between the PIC and gyrokinetic simulations, implying that gyrokinetics is capable of making accurate predictions well outside its regime of formal applicability. These results imply that in the large guide field limit many quantities resulting from the nonlinear evolution of reconnection ...

  9. Properties of large Li ion cells using a nickel based mixed oxide

    Science.gov (United States)

    Broussely, M.; Blanchard, Ph; Biensan, Ph; Planchat, J. P.; Nechev, K.; Staniewicz, R. J.

    The possible use of LiNiO 2 similar to LiCoO 2, as a positive material in rechargeable lithium batteries was recognized 20 years ago and starting 10 years later, many research studies led to material improvement through substitution of some of the nickel ions by other metallic ions. These modifications improve the thermal stability at high charge level or overcharge, as well as cycling and storage properties. Commercial material is now available at large industrial scale, which allows its use in big "industrial" Li ion batteries. Using low cost raw material (Ni), it is expected to be cost competitive with the manganese based systems usually mentioned as low cost on the total cell $/Wh basis. Providing higher energy density, and demonstrating excellent behavior on storage and extended cycle life, LiNiO 2 has definite advantages over the manganese system. Thanks to their properties, these batteries have demonstrated their ability to be used in lot of applications, either for transportation or standby. Their light weight makes them attractive for powering satellites. Although safety improvements are always desirable for all non-aqueous batteries using flammable organic electrolytes, suitable battery designs allow the systems to reach the acceptable level of safety required by many users. Beside the largely distributed lead acid and nickel cadmium batteries, Li ion will found its place in the "industrial batteries" market, in a proportion directly linked to its future cost reduction.

  10. Live-cell multiphoton fluorescence correlation spectroscopy with an improved large Stokes shift fluorescent protein

    Science.gov (United States)

    Guan, Yinghua; Meurer, Matthias; Raghavan, Sarada; Rebane, Aleksander; Lindquist, Jake R.; Santos, Sofia; Kats, Ilia; Davidson, Michael W.; Mazitschek, Ralph; Hughes, Thomas E.; Drobizhev, Mikhail; Knop, Michael; Shah, Jagesh V.

    2015-01-01

    We report an improved variant of mKeima, a monomeric long Stokes shift red fluorescent protein, hmKeima8.5. The increased intracellular brightness and large Stokes shift (∼180 nm) make it an excellent partner with teal fluorescent protein (mTFP1) for multiphoton, multicolor applications. Excitation of this pair by a single multiphoton excitation wavelength (MPE, 850 nm) yields well-separable emission peaks (∼120-nm separation). Using this pair, we measure homo- and hetero-oligomerization interactions in living cells via multiphoton excitation fluorescence correlation spectroscopy (MPE-FCS). Using tandem dimer proteins and small-molecule inducible dimerization domains, we demonstrate robust and quantitative detection of intracellular protein–protein interactions. We also use MPE-FCCS to detect drug–protein interactions in the intracellular environment using a Coumarin 343 (C343)-conjugated drug and hmKeima8.5 as a fluorescence pair. The mTFP1/hmKeima8.5 and C343/hmKeima8.5 combinations, together with our calibration constructs, provide a practical and broadly applicable toolbox for the investigation of molecular interactions in the cytoplasm of living cells. PMID:25877871

  11. Pregnancy and cavernous sinus syndrome in diffuse large B-cell lymphoma

    Directory of Open Access Journals (Sweden)

    Juan Wang

    2013-01-01

    Full Text Available Diffuse large B-cell lymphoma (DLBCL usually present with rapidly growing lymph nodes or extra-nodal masses. Central nerve system involvement and pregnancy are rare in DLBCL. Here, we report an unusual case of DLBCL with cavernous sinus syndrome during pregnancy. A 24-year-old woman presented cavernous sinus syndrome as the initial presentation during pregnancy. Magnetic resonance imaging (MRI revealed enlargement of bilateral cavernous sinus. Tonsil and ovary biopsy indicated malignant lymphoma-DLBCL. Bone marrow smear showed infiltration by tumor cells. The case delivered a viable baby by cesarean section and then took chemotherapy of rituxan, cyclophosphamide, adriamycin, eldisine and dexamethasone. The disease deteriorated rapidly, especially after the pregnancy was terminated. Fortunately, a complete response was achieved after six cycles of chemotherapy. With the accumulation of clinical practice of such cases, we would be able to recognize minimal symptoms of DLBCL at the beginning and confirm the most suitable timing of the initiation of chemotherapy during pregnancy.

  12. Primary Diffuse Large B-Cell Lymphoma of the Liver in a Patient with Sjogren Syndrome

    Directory of Open Access Journals (Sweden)

    Vadim Gorodetskiy

    2016-01-01

    Full Text Available Sjögren’s syndrome (SS has the highest incidence of malignant lymphoproliferative disorders transformation among autoimmune diseases. We present a case of extranodal high grade lymphoma of the liver in a 52-year-old patient with long history of SS. Lymphoma manifested with sharp significant pain in the right hypochondrium, weakness, and profuse night sweats. Contrast-enhanced computed tomography scan (CT-scan of the abdomen revealed multiple low density foci with homogeneous structure and clear contours in both lobes of the liver. Histologically, proliferation of medium sized lymphoma cells with round-oval and slightly irregular nuclei with fine chromatin was shown. Immunohistochemical and molecular features of the tumors allowed diagnosis of diffuse large B-cell lymphoma (DLBCL. To exclude secondary liver lesion by non-Hodgkin lymphoma, chest and small pelvis CT-scan, endoscopy of upper and lower gastrointestinal tract and study of bone marrow were performed. After 8 cycles of R-CHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, the complete remission was achieved, which persists after 45 months of follow-up. Primary hepatic lymphomas are extremely rare, and previously only low-grade hepatic lymphomas have been described in SS. To our knowledge, the patient described here represents the first reported case of DLBCL with primary liver involvement in SS.

  13. Pulmonary Large Cell Carcinoma Displays High Expression of EMMPRIN and VEGF

    Institute of Scientific and Technical Information of China (English)

    Yushuang Zheng; Miao Yu; Huachuan Zheng; Yifu Guan; Yasuo Takano

    2008-01-01

    OBJECTIVE To investigate the expression of extracellular matrix metalloproteinase inducer (EMMPRIN) and vascular endothelial growth factor (VEGF) in lung carcinomas,and to clarify their roles in carcinoma progression.METHODS Expression of EMMPRIN and VEGF was examined with tissue microarrays (TMAs) of lung carcinomas (n = 181),and their suppression in adjacent normal lung samples (n = 40) were determined by immunohistochemistry.The results were compared with clinicopathological findings for the same tumors.RESULTS Both EMMPRIN and VEGF were occasionally expressed in pseudostratified columnar epithelium and frequently in lung carcinomas.Histologically,EMMPRIN and VEGF displayed higher levels in large (LCC) cell carcinomas than adenocarcinoma (AD),squamous (SQ) and small cell carcinomas (SCC) (P < 0.05).EMMPRIN was more highly expressed in SQ as compared with AD (P < 0.05),while the converse was true for VEGF (P < 0.05).Binding was generally more intense for EMMPRIN in samples from male compared to female patients (P < 0.05),whereas the latter tended to exhibit more VEGF expression (P < 0.05).Positive associations of VEGF expression with the TNM stage and amounts of EMMPRIN were noted in the lung carcinomas (P < 0.05).CONCLUSION EMMPRIN and VEGF possibly contribute to physiological repair of normal lung and histogenesis of lung carcinoma.Both proteins might be involved in the molecular basis for differences in the incidence of lung carcinoma between men and women.

  14. Large-scale production of megakaryocytes from human pluripotent stem cells by chemically defined forward programming.

    Science.gov (United States)

    Moreau, Thomas; Evans, Amanda L; Vasquez, Louella; Tijssen, Marloes R; Yan, Ying; Trotter, Matthew W; Howard, Daniel; Colzani, Maria; Arumugam, Meera; Wu, Wing Han; Dalby, Amanda; Lampela, Riina; Bouet, Guenaelle; Hobbs, Catherine M; Pask, Dean C; Payne, Holly; Ponomaryov, Tatyana; Brill, Alexander; Soranzo, Nicole; Ouwehand, Willem H; Pedersen, Roger A; Ghevaert, Cedric

    2016-01-01

    The production of megakaryocytes (MKs)-the precursors of blood platelets-from human pluripotent stem cells (hPSCs) offers exciting clinical opportunities for transfusion medicine. Here we describe an original approach for the large-scale generation of MKs in chemically defined conditions using a forward programming strategy relying on the concurrent exogenous expression of three transcription factors: GATA1, FLI1 and TAL1. The forward programmed MKs proliferate and differentiate in culture for several months with MK purity over 90% reaching up to 2 × 10(5) mature MKs per input hPSC. Functional platelets are generated throughout the culture allowing the prospective collection of several transfusion units from as few as 1 million starting hPSCs. The high cell purity and yield achieved by MK forward programming, combined with efficient cryopreservation and good manufacturing practice (GMP)-compatible culture, make this approach eminently suitable to both in vitro production of platelets for transfusion and basic research in MK and platelet biology. PMID:27052461

  15. Thermoeconomic analysis of large solid oxide fuel cell plants: Atmospheric vs. pressurized performance

    International Nuclear Information System (INIS)

    A detailed thermoeconomic analysis of two large solid oxide fuel cell-based power plants operating at atmospheric pressure and 20 bar, respectively, is assessed in this work. The analyzed systems employ SOFC-GT (gas turbine) modules as main power generators; a bottom HRSC (heat recovery steam cycle) to generate additional electricity from the SOFC-GT exhaust hot gases is also included. The thermodynamic and economic performance of the two plant configurations are studied in detail: the exergy analysis shows an enhanced exergetic performance for the pressurized cycle that features components with higher efficiency and consequently a lower rate of exergy destruction (∼20% less than the atmospheric plant). The economic analysis considers the capital cost of each component within the system and is developed aiming at estimating the levelized cost of electricity. In order to match both exergetic and economic parts, a rigorous thermoeconomic analysis following the theory of Valero and Bejan [1,2] is implemented. A well-defined set of rules for the exergoeconomic balance around each plant component is specified and specific cost balance equations are thus derived. Results show how pressurized plant outperforms the atmospheric one, with a (on exergo-economic base) cost of electricity of 47.7 $/MWh instead of 64.2 $/MWh. Therefore, both exergetic and economic advantages result from the adoption of a pressurized SOFC-GT cycle in the framework of future advance power plants based on high-temperature fuel cells. - Highlights: • Exergy analysis of atmospheric and pressurized SOFC plants. • Exergy destruction in a fuel cell hybrid power plant. • Rigorous thermoeconomic methodology to assess the performance of different power generation plants. • Economic performance of SOFC plants

  16. Machine learning‐based classification of diffuse large B‐cell lymphoma patients by eight gene expression profiles

    OpenAIRE

    Zhao, Shuangtao; Dong, Xiaoli; Shen, Wenzhi; Ye, Zhen; Xiang, Rong

    2016-01-01

    Abstract Gene expression profiling (GEP) had divided the diffuse large B‐cell lymphoma (DLBCL) into molecular subgroups: germinal center B‐cell like (GCB), activated B‐cell like (ABC), and unclassified (UC) subtype. However, this classification with prognostic significance was not applied into clinical practice since there were more than 1000 genes to detect and interpreting was difficult. To classify cancer samples validly, eight significant genes ( MYBL1, LMO2, BCL6, MME, IRF4, NFKBIZ, PDE4...

  17. Diffuse large B-Cell lymphoma: a clinico- pathologic and prognostic study on 1470 biopsy specimens

    Directory of Open Access Journals (Sweden)

    Sadighi S

    2009-11-01

    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Diffuse large B Cell lymphoma (DLBCL is the most common subtype of non-Hogkin lymphoma (NHL. We performed a retrospective study of patients with de novo DLBCL treated in the Medical Oncology department of Cancer Institute of Iran, Tehran to assess the clinicopathologic and immunohistochemistry correlation and prognosis of the patients. "n"nMethods: World Health Organization (WHO classification was used to reexamine 1470 biopsy specimens related to the years 1985-2006. After excluding five cases of T Cell large cell lymphoma, 50 Patients diagnosed as DLBCL. "n"nResults: Median age of the patients was 45.5(20-85 years: 60% were male and 30% had primary extranodal disease. The most common extranodal sites were bone, gastrointestinal tract and Head and neck areas. The most common stages were stage II (32%, stage III (32%, stage IV (20% and stage I (16% retrospectively and 33% had B-symptoms. All of The Patients received chemotherapy (83% CHOP regimen and 46% treated by radiotherapy after chemotherapy. With a mean follow up time of 32 months, median survival time was 34 (95% CI 24-40 months. Prognostic factors for survival were tumor stage, B-symptoms and early relapse (less than 6 months."n"nConclusions: Our

  18. 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

  19. Rationalization design on large equipment dismantling facility. The cell fire-extinguishing examination. 1. Technical report

    International Nuclear Information System (INIS)

    In order to rationalize for Large Equipment Dismantling Facility (LEDF), the plan of removing vaporizer belong to Cell-fire-extinguishing-system was investigated. In this test, in order to study the behavior of pressure in cell, when the liquefaction carbon dioxide (liq-CO2) is emitted, and the performance of extinguishing fires, the test of behavior. of pressure and the extinguishing fires take effect. Also the extinguishing fires test used water-mist take effect for complement liq-CO2. The results as follows; (1) In the test of behavior of pressure, Liq-CO2 was emitted test room under -40 mmAq negative pressure. Room pressure was increase about 0.8 mmAq/sec at first. After 20 sec, the pressure was increase slowly about 0.1 mmAq/sec. After 120 sec,the increase was drastic about 1.5 mmAq/s. (2) In the test of extinguishing fires by liq-CO2, under -40 mmAq, Polyethylene and wooden chips + cotton (crib) was burn. Polyethylene was extinguished perfectly, but the embers remained in cribs. While the room pressure was increase about 1.3 mmAq/sec for 10 sec at first. After 30 sec, the pressure was increase about 1 mmAq/sec. On the other hand, the drastic increase of pressure disappeared between 100 sec to 120 sec by change the nozzle size from 14 mm2 to 10 mm2. (3) In the test of extinguishing fires by water-mist, Cribs was extinguished perfectly, but Polyethylene was extinguished difficulty under the same condition of liq-CO2 test. (4) Therefore the results, It's coped with the fire extinguishing and the keeping negative 2 pressure for LEDF cells. Therefore nozzle size is fitted cell volume as changing 14 mm2 to 10 mm2 (5) As the performance of extinguishing fires by liq-CO2, It is necessity the concentration of above 50% CO2 for combustibles as cribs, remaining the embers. (6) On the other hand, It is necessity most study for the adoption of water-mist. Therefore water-mist was not effective for polyethylene, and it needed water for fire in great volume. (author)

  20. Biogrid--a microfluidic device for large-scale enzyme-free dissociation of stem cell aggregates.

    Science.gov (United States)

    Wallman, Lars; Åkesson, Elisabet; Ceric, Dario; Andersson, Per Henrik; Day, Kelly; Hovatta, Outi; Falci, Scott; Laurell, Thomas; Sundström, Erik

    2011-10-01

    Culturing stem cells as free-floating aggregates in suspension facilitates large-scale production of cells in closed systems, for clinical use. To comply with GMP standards, the use of substances such as proteolytic enzymes should be avoided. Instead of enzymatic dissociation, the growing cell aggregates may be mechanically cut at passage, but available methods are not compatible with large-scale cell production and hence translation into the clinic becomes a severe bottle-neck. We have developed the Biogrid device, which consists of an array of micrometerscale knife edges, micro-fabricated in silicon, and a manifold in which the microgrid is placed across the central fluid channel. By connecting one side of the Biogrid to a syringe or a pump and the other side to the cell culture, the culture medium with suspended cell aggregates can be aspirated, forcing the aggregates through the microgrid, and ejected back to the cell culture container. Large aggregates are thereby dissociated into smaller fragments while small aggregates pass through the microgrid unaffected. As proof-of-concept, we demonstrate that the Biogrid device can be successfully used for repeated passage of human neural stem/progenitor cells cultured as so-called neurospheres, as well as for passage of suspension cultures of human embryonic stem cells. We also show that human neural stem/progenitor cells tolerate transient pressure changes far exceeding those that will occur in a fluidic system incorporating the Biogrid microgrids. Thus, by using the Biogrid device it is possible to mechanically passage large quantities of cells in suspension cultures in closed fluidic systems, without the use of proteolytic enzymes. PMID:21850297

  1. 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

  2. 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

  3. Expression of a neuroendocrine gene signature in gastric tumor cells from CEA 424-SV40 large T antigen-transgenic mice depends on SV40 large T antigen.

    Directory of Open Access Journals (Sweden)

    Fritz Ihler

    Full Text Available BACKGROUND: A large fraction of murine tumors induced by transgenic expression of SV40 large T antigen (SV40 TAg exhibits a neuroendocrine phenotype. It is unclear whether SV40 TAg induces the neuroendocrine phenotype by preferential transformation of progenitor cells committed to the neuroendocrine lineage or by transcriptional activation of neuroendocrine genes. METHODOLOGY/PRINCIPAL FINDINGS: To address this question we analyzed CEA424-SV40 TAg-transgenic mice that develop spontaneous tumors in the antral stomach region. Immunohistology revealed expression of the neuroendocrine marker chromogranin A in tumor cells. By ELISA an 18-fold higher level of serotonin could be detected in the blood of tumor-bearing mice in comparison to nontransgenic littermates. Transcriptome analyses of antral tumors combined with gene set enrichment analysis showed significant enrichment of genes considered relevant for human neuroendocrine tumor biology. This neuroendocrine gene signature was also expressed in 424GC, a cell line derived from a CEA424-SV40 TAg tumor, indicating that the tumor cells exhibit a similar neuroendocrine phenotype also in vitro. Treatment of 424GC cells with SV40 TAg-specific siRNA downregulated expression of the neuroendocrine gene signature. CONCLUSIONS/SIGNIFICANCE: SV40 TAg thus appears to directly induce a neuroendocrine gene signature in gastric carcinomas of CEA424-SV40 TAg-transgenic mice. This might explain the high incidence of neuroendocrine tumors in other murine SV40 TAg tumor models. Since the oncogenic effect of SV40 TAg is caused by inactivation of the tumor suppressor proteins p53 and RB1 and loss of function of these proteins is commonly observed in human neuroendocrine tumors, a similar mechanism might cause neuroendocrine phenotypes in human tumors.

  4. 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.)

  5. Primary uterine diffuse large B-cell lymphoma involving the urinary bladder with urinary cytology mimicking carcinomas: A case report

    Directory of Open Access Journals (Sweden)

    Sumiyo Adachi

    2015-01-01

    Full Text Available We report a rare case of a 69-year-old woman in whom diffuse large B-cell lymphoma (DLBCL originated from the uterus and involved the urinary bladder. The cervical smears of the case mostly consisted of discohesive atypical round cells, which were highly suggestive of lymphoma; however, in voided urine smears, a majority of the cells formed large aggregates of degenerated cells, mimicking those of urothelial carcinoma (UC. The smears also represented some small loose clusters, in which tumor cells formed short chains with nuclear molding, mimicking those of small cell carcinoma. The cytodiagnosis got definitive when we identified the atypical cells that showed CD20+/CD3-/cytokeratin-/NSE- immunophenotype. These are of particular concern as they may have misleading similarities to other epithelial neoplasms when examining lymphoma involving the urinary bladder. Accordingly, this case highlights the importance of immunocytochemistry to rule out malignant lymphoma when encountering large and/or small loose clusters of atypical round cells on urinary cytology.

  6. Primary uterine diffuse large B-cell lymphoma involving the urinary bladder with urinary cytology mimicking carcinomas: A case report.

    Science.gov (United States)

    Adachi, Sumiyo; Yamazaki, Kazuto; Liang, Shan-Guang; Ishida, Yasuo

    2015-01-01

    We report a rare case of a 69-year-old woman in whom diffuse large B-cell lymphoma (DLBCL) originated from the uterus and involved the urinary bladder. The cervical smears of the case mostly consisted of discohesive atypical round cells, which were highly suggestive of lymphoma; however, in voided urine smears, a majority of the cells formed large aggregates of degenerated cells, mimicking those of urothelial carcinoma (UC). The smears also represented some small loose clusters, in which tumor cells formed short chains with nuclear molding, mimicking those of small cell carcinoma. The cytodiagnosis got definitive when we identified the atypical cells that showed CD20+/CD3-/cytokeratin-/NSE- immunophenotype. These are of particular concern as they may have misleading similarities to other epithelial neoplasms when examining lymphoma involving the urinary bladder. Accordingly, this case highlights the importance of immunocytochemistry to rule out malignant lymphoma when encountering large and/or small loose clusters of atypical round cells on urinary cytology. PMID:26729979

  7. B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma: Report of a case in the oral cavity

    Directory of Open Access Journals (Sweden)

    Jumana M Jaradat

    2013-01-01

    Full Text Available B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma (DLBCL/BL is a new category of B-cell lymphoma according to the 4 th edition of the World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues (2008. The following report presents a case of this rare, newly described entity on the palate of a 59 year-old male.

  8. Clinical analysis of 50 Eastern Asian patients with primary pulmonary large-cell neuroendocrine carcinoma

    Directory of Open Access Journals (Sweden)

    Zhang XK

    2015-05-01

    Full Text Available Xin-ke Zhang,1,* Tao Qin,1,* Yin-duo Zeng,1,2,* Yuan-yuan Zhao,1 Xue Hou,1 Wen-feng Fang,1 Shao-dong Hong,1 Ting Zhou,1 Zhi-huang Hu,1 Yun-peng Yang,1 Yu-xiang Ma,1 Cong Xue,1 Yan Huang,1 Hong-yun Zhao,1 Li Zhang1 1Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 2Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Background: To understand the clinicopathological features of patients with primary pulmonary large-cell neuroendocrine carcinoma (LCNEC, including the frequency of epidermal growth factor receptor (EGFR mutation, and to explore prognostic factors.Methods: We investigated a cohort of 50 individuals from our center database who were diagnosed with operable pulmonary LCNEC and treated in Sun Yat-sen University Cancer Center. Serum albumin (ALB and neuron-specific enolase (NSE were also collected. Survival curves were obtained with the Kaplan–Meier method, and the differences between groups in survival were tested by the log-rank test.Results: The median age was 59 years (range, 40–80 years. Fourteen patients underwent mutational analysis of EGFR; of these, 12 had wild-type EGFR and the remaining two had EGFR mutations in exons. The median disease-free survival (DFS of pulmonary LCNEC was 49.3 months and that of overall survival (OS was not reached. DFS and OS were shorter for patients with decreased serum ALB than for patients with normal serum ALB (P=0.003 and P=0.004, respectively. Meanwhile, a high level of NSE was also significantly associated with short DFS and OS (P=0.005 and P=0.000, respectively. Multivariate analysis showed that decrease in serum ALB was an independent prognostic factor for OS (P=0.046.Conclusion: The frequency of EGFR mutation in LCNEC patients is low. Serum ALB and NSE levels are

  9. Diffuse large B-cell lymphoma of the breast: prognostic factors and treatment outcomes

    Directory of Open Access Journals (Sweden)

    Sun Y

    2016-04-01

    Full Text Available Yao Sun,1 Monika Joks,2 Li-Ming Xu,1 Xiu-Li Chen,1 Dong Qian,1 Jin-Qiang You,1 Zhi-Yong Yuan1 1Department of Radiation Oncology, CyberKnife Center, 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; 2Department of Hematology and Bone Marrow Transplantation, Poznan University of Medical Science, Poznan, Poland Background: The breast is a rare site of extranodal involvement of diffuse large B-cell lymphoma (DLBCL. We aimed to assess the clinical characteristics, prognostic factors, and treatment outcomes of breast DLBCL.Patients and methods: We retrospectively analyzed 113 patients (from our institution and the literature between 1973 and 2014. The primary end point was overall survival (OS. Kaplan–Meier OS curves were compared with the log-rank test. Cox regression analysis was applied to determine the prognostic factors for OS, progression-free survival (PFS, local control (LC, and cause-specific survival (CSS.Results: A total of 113 patients were included in the study: 42 cases from our hospital and 71 cases from 12 publications. The median age at diagnosis was 58 years. With a median follow-up time of 39.2 months, the estimated 5-year OS, PFS, LC, and CSS were 71.4%, 58.8%, 75.6%, and 74.9%, respectively. In multivariate analysis, more than four cycles of chemotherapy, having localized cancer, lumpectomy with or without axillary lymph node (ALN dissection, and low to low-to-intermediate International Prognostic Index were favorable factors for OS. For PFS, significant prognostic factors were rituximab use, B symptoms, and tumor size. As for the local group, lumpectomy with or without ALN dissection and more than four cycles of chemotherapy were favorable factors for OS. Tumor size >4 cm and nonuse of rituximab were adverse factors for PFS. Twenty-one patients (18.6% developed local relapse and 33 (29

  10. MicroRNA-142 is mutated in about 20% of diffuse large B-cell lymphoma

    International Nuclear Information System (INIS)

    MicroRNAs (miRNAs) are short 18–23 nucleotide long noncoding RNAs that posttranscriptionally regulate gene expression by binding to mRNA. Our previous miRNA profiling of diffuse large B-cell lymphoma (DLBCL) revealed a mutation in the seed sequence of miR-142-3p. Further analysis now showed that miR-142 was mutated in 11 (19.64%) of the 56 DLBCL cases. Of these, one case had a mutation in both alleles, with the remainder being heterozygous. Four mutations were found in the mature miR-142-5p, four in the mature miR-142-3p, and three mutations affected the miR-142 precursor. Two mutations in the seed sequence redirected miR-142-3p to the mRNA of the transcriptional repressor ZEB2 and one of them also targeted the ZEB1 mRNA. However, the other mutations in the mature miR-142-3p did not influence either the ZEB1 or ZEB2 3′ untranslated region (3′ UTR). On the other hand, the mutations affecting the seed sequence of miR-142-3p resulted in a loss of responsiveness in the 3′ UTR of the known miR-142-3p targets RAC1 and ADCY9. In contrast to the mouse p300 gene, the human p300 gene was not found to be a target for miR-142-5p. In one case with a mutation of the precursor, we observed aberrant processing of the miR-142-5p. Our data suggest that the mutations in miR-142 probably lead to a loss rather than a gain of function. This is the first report describing mutations of a miRNA gene in a large percentage of a distinct lymphoma subtype

  11. Immunohistochemical and molecular characteristics with prognostic significance in diffuse large B-cell lymphoma.

    Directory of Open Access Journals (Sweden)

    Carmen Bellas

    Full Text Available Diffuse large B-cell lymphoma (DLBCL is an aggressive non-Hodgkin lymphoma with marked biologic heterogeneity. We analyzed 100 cases of DLBCL to evaluate the prognostic value of immunohistochemical markers derived from the gene expression profiling-defined cell origin signature, including MYC, BCL2, BCL6, and FOXP1 protein expression. We also investigated genetic alterations in BCL2, BCL6, MYC and FOXP1 using fluorescence in situ hybridization and assessed their prognostic significance. BCL6 rearrangements were detected in 29% of cases, and BCL6 gene alteration (rearrangement and/or amplification was associated with the non-germinal center B subtype (non-GCB. BCL2 translocation was associated with the GCB phenotype, and BCL2 protein expression was associated with the translocation and/or amplification of 18q21. MYC rearrangements were detected in 15% of cases, and MYC protein expression was observed in 29% of cases. FOXP1 expression, mainly of the non-GCB subtype, was demonstrated in 37% of cases. Co-expression of the MYC and BCL2 proteins, with non-GCB subtype predominance, was observed in 21% of cases. We detected an association between high FOXP1 expression and a high proliferation rate as well as a significant positive correlation between MYC overexpression and FOXP1 overexpression. MYC, BCL2 and FOXP1 expression were significant predictors of overall survival. The co-expression of MYC and BCL2 confers a poorer clinical outcome than MYC or BCL2 expression alone, whereas cases negative for both markers had the best outcomes. Our study confirms that DLBCL, characterized by the co-expression of MYC and BCL2 proteins, has a poor prognosis and establishes a significant positive correlation with MYC and FOXP1 over-expression in this entity.

  12. The biological effect of large single doses: a possible role for non-targeted effects in cell inactivation.

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    Marlon R Veldwijk

    Full Text Available BACKGROUND AND PURPOSE: Novel radiotherapy techniques increasingly use very large dose fractions. It has been argued that the biological effect of large dose fractions may differ from that of conventional fraction sizes. The purpose was to study the biological effect of large single doses. MATERIAL AND METHODS: Clonogenic cell survival of MCF7 and MDA-MB-231 cells was determined after direct X-ray irradiation, irradiation of feeder cells, or transfer of conditioned medium (CM. Cell-cycle distributions and the apoptotic sub-G1 fraction were measured by flow cytometry. Cytokines in CM were quantified by a cytokine antibody array. γH2AX foci were detected by immunofluorescence microscopy. RESULTS: The surviving fraction of MCF7 cells irradiated in vitro with 12 Gy showed an 8.5-fold decrease (95% c.i.: 4.4-16.3; P<0.0001 when the density of irradiated cells was increased from 10 to 50×10(3 cells per flask. Part of this effect was due to a dose-dependent transferrable factor as shown in CM experiments in the dose range 5-15 Gy. While no effect on apoptosis and cell cycle distribution was observed, and no differentially expressed cytokine could be identified, the transferable factor induced prolonged expression of γH2AX DNA repair foci at 1-12 h. CONCLUSIONS: A dose-dependent non-targeted effect on clonogenic cell survival was found in the dose range 5-15 Gy. The dependence of SF on cell numbers at high doses would represent a "cohort effect" in vivo. These results support the hypothesis that non-targeted effects may contribute to the efficacy of very large dose fractions in radiotherapy.

  13. Combinatorial BTK and MALT1 inhibition augments killing of CD79 mutant diffuse large B cell lymphoma

    OpenAIRE

    Nagel, Daniel; Bognar, Miriam; Eitelhuber, Andrea C; Kutzner, Kerstin; Vincendeau, Michelle; Krappmann, Daniel

    2015-01-01

    Survival of activated B cell-subtype (ABC) of diffuse large B cell lymphoma (DLBCL) is driven by chronic B cell receptor (BCR) signaling that activates the canonical NF-κB pathway. Inhibition of BTK by Ibrutinib has been shown to kill ABC DLBCL cells that carry activating mutations in the BCR adaptor CD79. However, mutations in BTK or in downstream components such as CARMA1/CARD11 can render lymphomas Ibrutinib resistant. Therefore, we assessed here the simultaneous inhibition of BTK and the ...

  14. MYC Negative Rectal B-Cell Lymphoma, Unclassifiable, with Features Intermediate between Diffuse Large B-Cell Lymphoma and Burkitt’s Lymphoma in an Immunocompetent Patient

    OpenAIRE

    Parikh, Jignesh G.; Ted Strom; Ilya Stone

    2013-01-01

    B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt’s lymphoma (BLUI) is a recently added entity to the World Health Organization (WHO) classification to address a grey zone between large B-cell lymphoma (DLBCL) and Burkitt’s lymphoma (BL). These are rare aggressive lymphomas, which were previously also known as Burkitt’s-like lymphoma (BLL). BL and BLUI/BLL of the colon mostly involve the ileocecal region. In the rectum, BL and BLUI/B...

  15. Morphologic characterization and distribution of endocrine cells in the large intestine of the opossum Didelphis aurita (Wied-Neuwied, 1826).

    Science.gov (United States)

    Dos Santos, Daiane Cristina Marques; Cupertino, Marli do Carmo; Novaes, Rômulo Dias; Soares, Ítalo Augusto da Costa; Fonseca, Cláudio César; da Matta, Sérgio Luis Pinto; Sartori, Sirlene Souza Rodrigues

    2013-10-01

    This study was designed to investigate the morphology and distribution of argyrophil, argentaffins, and insulin-immunoreactive endocrine cells in the large intestine of the opossum Didelphis aurita. Fragments of the large intestine of 10 male specimens of the opossum D. aurita were collected, processed, and submitted for histochemistry, immunohistochemistry, and scanning electron microscopy. The tunics of the large intestine of D. aurita presented morphological characteristics that have already been described for eutherian mammals. The morphometric data showed that the inner circular layer of all portions and regions analyzed is thicker relative to the longitudinal layer, and these layers in the rectum are thicker compared to the cecum and ascending colon. The majority of mucus-secreting cells have acid and neutral mucins, suggesting that the production of mucus is mixed. The number of these cells increases in the region of the cecum toward the rectum. Important findings include the occurrence of argyrophil, argentaffins, and insulin-immunoreactive endocrine cells in all segments of the large intestine of the opossum (D. aurita). To the best of our knowledge, this is the first report about the presence of insulin-immunoreactive endocrine cells in the large intestine of the opossum (D. aurita). PMID:23810437

  16. Extensive closed cell marine stratocumulus downwind of Europe—A large aerosol cloud mediated radiative effect or forcing?

    Science.gov (United States)

    Goren, Tom; Rosenfeld, Daniel

    2015-06-01

    Marine stratocumulus clouds (MSC) cover large areas over the oceans and possess super sensitivity of their cloud radiative effect to changes in aerosol concentrations. Aerosols can cause transitions between regimes of fully cloudy closed cells and open cells. The possible role of aerosols in cloud cover has a big impact on the amount of reflected solar radiation from the clouds, thus potentially constitutes very large aerosol indirect radiative effect, which can exceed 100 Wm-2. It is hypothesized that continentally polluted clouds remain in closed cells regime for longer time from leaving continent and hence for longer distance away from land, thus occupying larger ocean areas with full cloud cover. Attributing this to anthropogenic aerosols would imply a very large negative radiative forcing with a significant climate impact. This possibility is confirmed by analyzing a detailed case study based on geostationary and polar-orbiting satellite observations of the microphysical and dynamical evolution of MSC. We show that large area of closed cells was formed over the northeast Atlantic Ocean downwind of Europe in a continentally polluted air mass. The closed cells undergo cleansing process that was tracked for 3.5 days that resulted with a rapid transition from closed to open cells once the clouds started drizzling heavily. The mechanism leading to the eventual breakup of the clouds due to both meteorological and aerosol considerations is elucidated. We termed this cleansing and cloud breakup process maritimization. Further study is needed to assess the climatological significance of such situations.

  17. High-throughput combinatorial screening identifies drugs that cooperate with ibrutinib to kill activated B-cell-like diffuse large B-cell lymphoma cells.

    Science.gov (United States)

    Mathews Griner, Lesley A; Guha, Rajarshi; Shinn, Paul; Young, Ryan M; Keller, Jonathan M; Liu, Dongbo; Goldlust, Ian S; Yasgar, Adam; McKnight, Crystal; Boxer, Matthew B; Duveau, Damien Y; Jiang, Jian-Kang; Michael, Sam; Mierzwa, Tim; Huang, Wenwei; Walsh, Martin J; Mott, Bryan T; Patel, Paresma; Leister, William; Maloney, David J; Leclair, Christopher A; Rai, Ganesha; Jadhav, Ajit; Peyser, Brian D; Austin, Christopher P; Martin, Scott E; Simeonov, Anton; Ferrer, Marc; Staudt, Louis M; Thomas, Craig J

    2014-02-11

    The clinical development of drug combinations is typically achieved through trial-and-error or via insight gained through a detailed molecular understanding of dysregulated signaling pathways in a specific cancer type. Unbiased small-molecule combination (matrix) screening represents a high-throughput means to explore hundreds and even thousands of drug-drug pairs for potential investigation and translation. Here, we describe a high-throughput screening platform capable of testing compounds in pairwise matrix blocks for the rapid and systematic identification of synergistic, additive, and antagonistic drug combinations. We use this platform to define potential therapeutic combinations for the activated B-cell-like subtype (ABC) of diffuse large B-cell lymphoma (DLBCL). We identify drugs with synergy, additivity, and antagonism with the Bruton's tyrosine kinase inhibitor ibrutinib, which targets the chronic active B-cell receptor signaling that characterizes ABC DLBCL. Ibrutinib interacted favorably with a wide range of compounds, including inhibitors of the PI3K-AKT-mammalian target of rapamycin signaling cascade, other B-cell receptor pathway inhibitors, Bcl-2 family inhibitors, and several components of chemotherapy that is the standard of care for DLBCL. PMID:24469833

  18. Diffuse large B-cell lymphoma in the elderly: a review of potential difficulties.

    Science.gov (United States)

    Sarkozy, Clémentine; Coiffier, Bertrand

    2013-04-01

    Half of patients with diffuse large B-cell lymphoma (DLBCL) are more than 65 years old. These elderly patients frequently have other diseases, some of them severe, which may alter their ability to receive standard curative therapy. However, these associated diseases are heterogeneous and only a few contraindicate chemotherapy treatments. We reviewed all potential difficulties, such as the evaluation of comorbidities, the heterogeneous functional status of this population, and the consequences of the aging process that might be associated with treating these patients, and now propose solutions. As standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy may cure the majority of patients, it must always be the first proposed option. With this approach, elderly patients with DLBCL treated with a curative intent can reach a complete remission and have a similar outcome as younger patients. Reduced dose intensity must be applied for very elderly patients or those unfit for full-dose anthracycline. The critical question for a physician is why these patients cannot be treated with the standard regimen, namely R-CHOP. PMID:23339126

  19. Large-scale production of endotoxin-free plasmids for transient expression in mammalian cell culture.

    Science.gov (United States)

    Rozkov, Aleksei; Larsson, Bert; Gillström, Stefan; Björnestedt, Robert; Schmidt, Stefan R

    2008-02-15

    Transient expression of recombinant proteins in mammalian cell culture in a 100-L scale requires a large quantity of plasmid that is very labour intensive to achieve with shake flask cultures and commercially available plasmid purification kits. In this paper we describe a process for plasmid production in 100-mg scale. The fermentation is carried out in a 4-L fed-batch culture with a minimal medium. The detection of the end of batch and triggering the exponential (0.1 h(-1)) feed profile was unattended and controlled by Multi-fermenter Control System. A restricted specific growth rate in fed-batch culture increased the specific plasmid yield compared to batch cultures with minimal and rich media. This together with high biomass concentration (68-107 g L(-1) wet weight) achieves high volumetric yields of plasmid (95-277 mg L(-1) depending on the construct). The purification process consisted of alkaline lysis, lysate clarification and ultrafiltration, two-phase extraction with Triton X-114 for endotoxin removal, anion-exchange chromatography as a polishing step, ultrafiltration and sterile filtration. Both fermentation and purification processes were used without optimisation for production of four plasmids yielding from 39 to 163 mg of plasmids with endotoxin content of 2.5 EU mg(-1) or less. PMID:17680665

  20. [Central nervous system relapse in diffuse large B cell lymphoma: Risk factors].

    Science.gov (United States)

    Sancho, Juan-Manuel; Ribera, Josep-Maria

    2016-01-15

    Central nervous system (CNS) involvement by lymphoma is a complication associated, almost invariably, with a poor prognosis. The knowledge of the risk factors for CNS relapse is important to determine which patients could benefit from prophylaxis. Thus, patients with very aggressive lymphomas (such as lymphoblastic lymphoma or Burkitt's lymphoma) must systematically receive CNS prophylaxis due to a high CNS relapse rate (25-30%), while in patients with indolent lymphoma (such as follicular lymphoma or marginal lymphoma) prophylaxis is unnecessary. However, the question about CNS prophylaxis in patients with diffuse large B-cell lymphoma (DLBCL), the most common type of lymphoma, remains controversial. The information available is extensive, mainly based on retrospective and heterogeneous studies. There seems that immunochemotherapy based on rituximab reduces the CNS relapse rate. On the other hand, patients with increased serum lactate dehydrogenase plus more than one extranodal involvement seem to have a higher risk of CNS relapse, but a prophylaxis strategy based only on the presence of these 2 factors does not prevent all CNS relapses. Patients with involvement of testes or breast have high risk of CNS relapse and prophylaxis is mandatory. Finally, CNS prophylaxis could be considered in patients with DLBCL and renal or epidural space involvement, as well as in those cases with MYC rearrangements, although additional studies are necessary. PMID:25817451

  1. PET Scans for Staging and Restaging in Diffuse Large B-Cell and Follicular Lymphomas.

    Science.gov (United States)

    Barrington, Sally F; Mikhaeel, N George

    2016-06-01

    Positron emission tomography (PET)-CT was recommended in updated international guidelines for staging/restaging of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). In FL, PET was previously regarded as a research application only. This review concentrates on new publications related to PET in these diseases. In DLBCL, PET appears appropriate for staging using prognostic indices established with CT and baseline PET parameters, e.g. metabolic tumour volume, are prognostic of outcome. Early complete metabolic response (CMR) predicts end-of-treatment CMR with excellent prognosis. Patients without CMR at interim should not have treatment altered, but have a worse prognosis, and patients with other high risk features may need closer monitoring. The end-of-treatment scan is confirmed as the standard for remission assessment using Deauville criteria, which are also predictive for patients undergoing ASCT. In FL, PET is more sensitive for staging than CT but misses bone marrow involvement. PET-CT identifies patients at risk of progression after induction chemotherapy better than CT. PMID:27095319

  2. [REACTIVATION OF TUBERCULOSIS PRESENTING WITH EMPYEMA DUE TO ANTICANCER CHEMOTHERAPY FOR DIFFUSE LARGE B CELL LYMPHOMA].

    Science.gov (United States)

    Yuba, Tatsuya; Hatsuse, Mayumi; Kodama, Mai; Uda, Sayaka; Yoshimura, Akihiro; Kurisu, Naoko

    2016-04-01

    A 79-year-old man with a history of tuberculosis was found to have chronic empyema in the right lung and was diagnosed with malignant diffuse large-cell lymphoma (Ann Arbor stage IIE). After completion of one course of rituximab plus cyclophosphamide, pirarubicin, vincristine, and prednisolone (R-CHOP) chemotherapy, the patient developed lung abscess and sepsis caused by Streptococcus intermedius. This condition was treated with antimicrobial agents, and chemotherapy was resumed. After the second course, the chemotherapy regimen was continued without prednisolone, and after administration of the third course, a chest wall mass was found in the right lung. An acid-fast bacillus smear test of the abscess aspirate was positive, and Mycobacterium tuberculosis was detected in a polymerase chain reaction assay, leading to a diagnosis of perithoracic tuberculosis. Chemotherapy for the lymphoma was discontinued, and treatment with four oral antitubercular agents was started. This treatment led to remission of perithoracic tuberculosis. In Japan, tuberculous scar and chronic empyema are relatively common findings, and relapse of tuberculosis should always be considered for patients with these findings during chemotherapy and immunosuppressive therapy. PMID:27530021

  3. SILAC-Based Quantitative Proteomic Analysis of Diffuse Large B-Cell Lymphoma Patients

    Directory of Open Access Journals (Sweden)

    Ulla Rüetschi

    2015-01-01

    Full Text Available Diffuse large B-cell lymphoma (DLBCL, the most common lymphoma, is a heterogeneous disease where the outcome for patients with early relapse or refractory disease is very poor, even in the era of immunochemotherapy. In order to describe possible differences in global protein expression and network patterns, we performed a SILAC-based shotgun (LC-MS/MS quantitative proteomic analysis in fresh-frozen tumor tissue from two groups of DLBCL patients with totally different clinical outcome: (i early relapsed or refractory and (ii long-term progression-free patients. We could identify over 3,500 proteins; more than 1,300 were quantified in all patients and 87 were significantly differentially expressed. By functional annotation analysis on the 66 proteins overexpressed in the progression-free patient group, we found an enrichment of proteins involved in the regulation and organization of the actin cytoskeleton. Also, five proteins from actin cytoskeleton regulation, applied in a supervised regression analysis, could discriminate the two patient groups. In conclusion, SILAC-based shotgun quantitative proteomic analysis appears to be a powerful tool to explore the proteome in DLBCL tumor tissue. Also, as progression-free patients had a higher expression of proteins involved in the actin cytoskeleton protein network, such a pattern indicates a functional role in the sustained response to immunochemotherapy.

  4. Biomarkers of diffuse large B-cell lymphoma: impact on diagnosis, treatment, and prognosis

    Directory of Open Access Journals (Sweden)

    Coutinho R

    2013-02-01

    Full Text Available Rita Coutinho, John GribbenCentre for Haemato-Onocology, Barts Cancer Institute, Queen Mary, University of London, London, United KingdomAbstract: Introduction of immunochemotherapy as frontline treatment for diffuse large B-cell lymphoma (DLBCL has significantly increased survival. However, patients refractory to rituximab-containing regimens have a very poor survival. These differences in clinical behavior might lie behind the biological heterogeneity well recognized in this disease. Advanced molecular research has helped us to define DLBCL subgroups which harbor distinct oncogenic events and response to immunochemotherapy. The field of biomarker discovery in DLBCL has become more complex over the last decade and a broad up-to-date review on this topic is lacking. The aim for this review was to offer the hematology community a comprehensive overview of clinical and biological markers which have a diagnostic and prognostic potential and that might be amenable to therapeutic targeting. Some well known markers are reassessed in light of recent findings.Keywords: DLBCL, immunochemotherapy, rituximab, biomarkers

  5. Particle-in-cell simulation of large amplitude ion-acoustic solitons

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, Sarveshwar, E-mail: sarvsarvesh@gmail.com; Sengupta, Sudip; Sen, Abhijit [Institute for Plasma Research, Bhat, Gandhinagar 382 428 (India)

    2015-02-15

    The propagation of large amplitude ion-acoustic solitons is studied in the laboratory frame (x, t) using a 1-D particle-in-cell code that evolves the ion dynamics by treating them as particles but assumes the electrons to follow the usual Boltzmann distribution. It is observed that for very low Mach numbers the simulation results closely match the Korteweg-de Vries soliton solutions, obtained in the wave frame, and which propagate without distortion. The collision of two such profiles is observed to exhibit the usual solitonic behaviour. As the Mach number is increased, the given profile initially evolves and then settles down to the exact solution of the full non-linear Poisson equation, which then subsequently propagates without distortion. The fractional change in amplitude is found to increase linearly with Mach number. It is further observed that initial profiles satisfying k{sup 2}λ{sub de}{sup 2}<1 break up into a series of solitons.

  6. [Recent advances in the understanding and treatment of diffuse large B-cell lymphoma].

    Science.gov (United States)

    Gergely, Lajos; Illés, Árpád

    2016-07-01

    Diffuse large B-cell lymphoma is the most common type of non-Hodgkin's lymphoma. Using the conventional cyclophosphamide adriablastin vincristin prednisolon polychemotherapy about 50% of the patients were cured. The addition of rituximab to the regimen increased the cure rate to 60%. This is a major improvement, however, further advance is still needed to increase the cure rate. The extensive genetic testing performed recently revealed several important pathognomic mutations as potential targets in this disease. Routine diagnosis of patients now includes the use of (18)Fluor-deoxy-glucose positron emission computer tomography, according to the recent Lugano classification system. With all these data we can better predict the prognosis of patients, and we can select candidates for novel targeted therapies as well. Answering these questions, and utilizing novel therapies possibly will further increase the cure rate in the near future. This paper summarizes current diagnostic and therapeutic approaches and describes recent understanding in the mutations and pathognomic changes resulting in the disease. The authors also summarize the data available on experimental therapies possibly entering clinical pratice in the forthcoming years. Orv. Hetil., 2016, 157(31), 1232-1241. PMID:27476519

  7. Increased Chromogranin A Cell Density in the Large Intestine of Patients with Irritable Bowel Syndrome after Receiving Dietary Guidance

    Directory of Open Access Journals (Sweden)

    Tarek Mazzawi

    2015-01-01

    Full Text Available The large intestine contains five types of endocrine cells that regulate its functions by sensing its luminal contents and releasing specific hormones. Chromogranin A (CgA is a common marker for the gastrointestinal endocrine cells, and it is abnormal in irritable bowel syndrome (IBS patients. Most IBS patients relate their symptoms to certain food elements. The present study investigated the effect of dietary guidance on the total endocrine cells of the large intestine as detected by CgA in 13 IBS patients. Thirteen control subjects were also included. Each patient received three sessions of dietary guidance. Colonoscopies were performed on controls and patients (at baseline and at 3–9 months after receiving guidance. Biopsy samples from the colon and rectum were immunostained for CgA and quantified by computerized image analysis. The densities of CgA cells in the total colon (mean ± SEM among the controls and the IBS patients before and after receiving dietary guidance were 83.3±10.1, 38.6±3.7, and 64.7±4.2 cells/mm2, respectively (P=0.0004, and were unchanged in the rectum. In conclusion, the increase in CgA cell density after receiving dietary guidance may reflect a change in the densities of the large intestinal endocrine cells causing an improvement in the IBS symptoms.

  8. A vacuum flash-assisted solution process for high-efficiency large-area perovskite solar cells.

    Science.gov (United States)

    Li, Xiong; Bi, Dongqin; Yi, Chenyi; Décoppet, Jean-David; Luo, Jingshan; Zakeeruddin, Shaik Mohammed; Hagfeldt, Anders; Grätzel, Michael

    2016-07-01

    Metal halide perovskite solar cells (PSCs) currently attract enormous research interest because of their high solar-to-electric power conversion efficiency (PCE) and low fabrication costs, but their practical development is hampered by difficulties in achieving high performance with large-size devices. We devised a simple vacuum flash-assisted solution processing method to obtain shiny, smooth, crystalline perovskite films of high electronic quality over large areas. This enabled us to fabricate solar cells with an aperture area exceeding 1 square centimeter, a maximum efficiency of 20.5%, and a certified PCE of 19.6%. By contrast, the best certified PCE to date is 15.6% for PSCs of similar size. We demonstrate that the reproducibility of the method is excellent and that the cells show virtually no hysteresis. Our approach enables the realization of highly efficient large-area PSCs for practical deployment. PMID:27284168

  9. A vacuum flash–assisted solution process for high-efficiency large-area perovskite solar cells

    Science.gov (United States)

    Li, Xiong; Bi, Dongqin; Yi, Chenyi; Décoppet, Jean-David; Luo, Jingshan; Zakeeruddin, Shaik Mohammed; Hagfeldt, Anders; Grätzel, Michael

    2016-07-01

    Metal halide perovskite solar cells (PSCs) currently attract enormous research interest because of their high solar-to-electric power conversion efficiency (PCE) and low fabrication costs, but their practical development is hampered by difficulties in achieving high performance with large-size devices. We devised a simple vacuum flash–assisted solution processing method to obtain shiny, smooth, crystalline perovskite films of high electronic quality over large areas. This enabled us to fabricate solar cells with an aperture area exceeding 1 square centimeter, a maximum efficiency of 20.5%, and a certified PCE of 19.6%. By contrast, the best certified PCE to date is 15.6% for PSCs of similar size. We demonstrate that the reproducibility of the method is excellent and that the cells show virtually no hysteresis. Our approach enables the realization of highly efficient large-area PSCs for practical deployment.

  10. A Pilot Study to Evaluate the Co-Infusion of Ex Vivo Expanded Cord Blood Cells With an Unmanipulated Cord Blood Unit in Patients Undergoing Cord Blood Transplant for Hematologic Malignancies

    Science.gov (United States)

    2015-02-10

    Accelerated Phase Chronic Myelogenous Leukemia; Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Phase Chronic Myelogenous Leukemia; Contiguous Stage II Adult Burkitt Lymphoma; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Contiguous Stage II Adult Lymphoblastic Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Previously Treated Myelodysplastic Syndromes; Prolymphocytic Leukemia; Recurrent Adult Burkitt Lymphoma

  11. Plasma texturing on large-area industrial grade CZ silicon solar cells

    DEFF Research Database (Denmark)

    Davidsen, Rasmus Schmidt; Nordseth, Ørnulf; Boisen, Anja;

    2013-01-01

    , and thus holds a significant potential for improvement of the cell performance compared to current industrial standards. The reflectance is shown to remain below that of conventional textured cells also at high angle of incidence. The process is shown to be equally applicable to mono-, multi- and...... quasi-mono-crystalline Si. The process was successfully integrated in fabrication of solar cells using only industry standard processes on a Czochralski (CZ) silicon starting material. The resulting cell performance was compared to cells with conventional texturing. For cells, where the nanostructuring...

  12. MYC protein expression and genetic alterations have prognostic impact in diffuse large B-cell lymphoma treated with immunochemotherapy

    OpenAIRE

    Valera Barros, Alexandra; López Guillermo, Armando; Cardesa Salzmann, Antonio; Climent, Fina; González Barca, Eva; Mercadal, Santiago; Espinosa, Iñigo; Novelli, Silvana; Briones, Javier; Mate, José L.; Salamero, Olga; Sancho, Juan M.; Arenillas, Leonor; Serrano, Sergi; Erill, Nadina

    2013-01-01

    MYC alterations influence the survival of patients with diffuse large B-cell lymphoma. Most studies have focused on MYC translocations but there is little information regarding the impact of numerical alterations and protein expression. We analyzed the genetic alterations and protein expression of MYC, BCL2, BCL6, and MALT1 in 219 cases of diffuse large B-cell lymphoma. MYC rearrangement occurred as the sole abnormality (MYC single-hit) in 3% of cases, MYC and concurrent BCL2 and/or BCL6 rear...

  13. Pure Laparoscopic Radical Heminephrectomy for a Large Renal-Cell Carcinoma in a Horseshoe Kidney

    Directory of Open Access Journals (Sweden)

    Rafael B Reboucas

    2013-07-01

    Full Text Available Introduction Horseshoe Kidneys are the most common renal fusion anomaly. When surgery is contemplated for renal-cell carcinoma in such kidneys, aberrant vasculature and isthmusectomy are the major issues to consider. We describe a case of a pure laparoscopic radical heminephrectomy with hand-sewn management of the isthmus for a 11 cm tumour in a horseshoe kidney. Presentation A 47-year-old man complaining of palpable left flank mass for two months. Magnetic resonance of the abdomen revealed a 11 cm renal mass arising from the left moiety of an incidentally discovered horseshoe kidney. Preoperative CT angiography revealed a dominant anterior renal artery feeding the upper and midpole, with two other arteries feeding the lower pole and isthmus. The patient was placed in a modified flank position. A four-port transperitoneal technique was used, the colon was reflected. Renal pedicle was dissected and the renal arteries and renal vein were secured with polymer clips. The kidney was fully mobilized and a Satinsky clamp was placed on the isthmus for its division. A running 2-0 vicryl hand-sewn was used for parenchyma hemostasis. The specimen was extracted intact in a plastic bag through an inguinal incision. Results The operative time was 220 minutes, and the estimated blood loss was 200 mL. There were no immediate or delayed complications. The patient resumed oral intake on postoperative day 1 and was discharged on postoperative day 2. Pathologic examination of the specimen confirmed a 11 cm organ-confined chromophobe renal-cell carcinoma, with negative margins. Discussion Laparoscopic oncologic surgery in patients with horseshoe kidneys can be technically challenging. The presence of a large cancer in a horseshoe kidney should not preclude a purely laparoscopic approach. With the aid of a Satinsky clamp, the isthmus can be sharply divided and sutured in a fashion similar to the open technique. To our knowledge, this report represents the largest

  14. Optimized Packing Density of Large CZTS Nanoparticles Synthesized by Hot-injection for Thin Film Solar Cells.

    OpenAIRE

    Engberg, Sara Lena Josefin; Lam, Yeng Ming; Schou, Jørgen

    2015-01-01

    The absorbing kesterite material, Cu2ZnSn(SxSe1-x)4 (CZTS), is very promising for future thin film solar cells. The material is non-toxic, the elements abundant, and it has a high absorption coefficient. These properties make CZTS a potential candidate also for large-scale applications. Here, solution processing allows for comparatively fast and inexpensive fabrication, and also holds the record efficiency in the kesterite family. Unfortunately, the record cell is deposited with a highly toxi...

  15. Study of solid and liquid behavior in large copper flotation cells (130 m2) using radioactive tracers

    OpenAIRE

    Yianatos J.; Jiménez O.; Díaz F.; Contreras F.

    2013-01-01

    The behavior of the solid and liquid phases, in large flotation cells, was characterized by means of the radioactive tracer technique. The use of radioactive tracers enabled the identification of the Residence Time Distribution, of floatable and non-floatable solid, from continuous (on-line) measuring at the output streams of the flotation cells. For this study, the proper radioactive tracers were selected and applied in order to characterize the different phases; i.e. for liquid phase Br-82 ...

  16. CGCI Investigators Reveal Comprehensive Landscape of Diffuse Large B-Cell Lymphoma (DLBCL) Genomes | Office of Cancer Genomics

    Science.gov (United States)

    Researchers from British Columbia Cancer Agency used whole genome sequencing to analyze 40 DLBCL cases and 13 cell lines in order to fill in the gaps of the complex landscape of DLBCL genomes. Their analysis, “Mutational and structural analysis of diffuse large B-cell lymphoma using whole genome sequencing,” was published online in Blood on May 22. The authors are Ryan Morin, Marco Marra, and colleagues.  

  17. Modular Approach for Continuous Cell-Level Balancing to Improve Performance of Large Battery Packs: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Muneed ur Rehman, M.; Evzelman, M.; Hathaway, K.; Zane, R.; Plett, G. L.; Smith, K.; Wood, E.; Maksimovic, D.

    2014-10-01

    Energy storage systems require battery cell balancing circuits to avoid divergence of cell state of charge (SOC). A modular approach based on distributed continuous cell-level control is presented that extends the balancing function to higher level pack performance objectives such as improving power capability and increasing pack lifetime. This is achieved by adding DC-DC converters in parallel with cells and using state estimation and control to autonomously bias individual cell SOC and SOC range, forcing healthier cells to be cycled deeper than weaker cells. The result is a pack with improved degradation characteristics and extended lifetime. The modular architecture and control concepts are developed and hardware results are demonstrated for a 91.2-Wh battery pack consisting of four series Li-ion battery cells and four dual active bridge (DAB) bypass DC-DC converters.

  18. Prognostic value of tumor necrosis at CT in diffuse large B-cell lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Adams, Hugo J.A., E-mail: h.j.a.adams@gmail.com [Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht (Netherlands); Klerk, John M.H. de [Department of Nuclear Medicine, Meander Medical Center, Amersfoort (Netherlands); Fijnheer, Rob [Department of Hematology, Meander Medical Center, Amersfoort (Netherlands); Dubois, Stefan V. [Department of Pathology, Meander Medical Center, Amersfoort (Netherlands); Nievelstein, Rutger A.J.; Kwee, Thomas C. [Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht (Netherlands)

    2015-03-15

    Highlights: •CT is compulsory for staging newly diagnosed DLBCL. •Approximately 13.7% of DLBCL patients have tumor necrosis at CT. •Tumor necrosis status at CT is not associated with any NCCN-IPI factor. •Patients with tumor necrosis at CT have a significantly worse outcome. -- Abstract: Objective: To determine the prognostic value of tumor necrosis at computed tomography (CT) in newly diagnosed diffuse large B-cell lymphoma (DLBCL). Materials and methods: This retrospective study included 51 patients with newly diagnosed DLBCL who had undergone both unenhanced and intravenous contrast-enhanced CT before R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin and prednisolone) chemo-immunotherapy. Presence of tumor necrosis was visually and quantitatively assessed at CT. Associations between tumor necrosis status at CT and the National Comprehensive Cancer Network (NCCN) International Prognostic Index (IPI) factors were assessed. Cox regression analysis was used to determine the prognostic impact of NCCN-IPI scores and tumor necrosis status at CT. Results: There were no correlations between tumor necrosis status at CT and the NCCN-IPI factors categorized age (ρ = −0.042, P = 0.765), categorized lactate dehydrogenase (LDH) ratio (ρ = 0.201, P = 0.156), extranodal disease in major organs (φ = −0.245, P = 0.083), Ann Arbor stage III/IV disease (φ = −0.208, P = 0.141), and Eastern Cooperative Oncology Group (ECOG) performance status (φ = 0.015, P = 0.914). In the multivariate Cox proportional hazards model, only tumor necrosis status at CT was an independent predictive factor of progression-free survival (P = 0.003) and overall survival (P = 0.004). Conclusion: The findings of this study indicate the prognostic potential of tumor necrosis at CT in newly diagnosed DLBCL.

  19. Correlation of genes associated with drug response to prognosis of large cell lung carcinoma

    Institute of Scientific and Technical Information of China (English)

    Cheng Chen; Xiang-Li Jiang; Cui-Cui Zhang; Kai Li

    2011-01-01

    Platinum-based chemotherapy remains the main treatment of advanced lung cancer. However,platinum resistance has become a major treatment obstacle. Novel therapies, particularly tyrosine kinase inhibitors of the epidermal growth factor receptor (EGFR-TKI) and agents that target vascular endothelial growth factor (VEGF), have improved the treatment. Both chemotherapy and targeted therapy have their molecular mechanisms. This study aimed to determine the mutation, amplification, or expression status and interrelationships of the epidermal growth factor receptor (EGFR), K-Ras proto-oncogene, excision repair cress-complementation group 1 (ERCC1), and VEGF genes as well as their correlations to prognosis of large cell lung carcinoma (LCLC) after EGFR-targeted therapy, chemotherapy, and antiVEGF therapy. EGFR and K-Ras mutations in 60 specimens of LCLC were detected by direct DNA sequencing. EGFR, ERCC1, and VEGF protein expression was detected by immunohistochemistry (IHC).EGFR gene copy number was detected by fluorescence in situ hybridization (FISH). One (1.7%) patient had an EGFR L858M point mutation in exon 21, 3 (5.0%) had K-Ras mutations, and 10 (19.6%) had EGFR amplification (FISH positive). Positive rates of EGFR, ERCC1, and VEGF proteins were 38.3%,56.7%, and 70.0%, respectively. EGFR amplification was positively correlated to EGFR protein expression (r = 0.390, P = 0.005). The positive rate of VEGF protein was significantly higher in patients with lymph node metastasis than in those without (84.6% vs. 58.8%, P = 0.046). No significant correlations were observed among the EGFR, K-Ras, ERCC1, and VEGF genes. EGFR gene amplification and the low rate of EGFR mutation suggest that patients with LCLC are likely to obtain little benefit from anti-EGFR therapies.

  20. Comparative Study on Rituximab Combined with Chemotherapy and Single Chemotherapy for Diffuse Large B Cell Lymphoma

    Institute of Scientific and Technical Information of China (English)

    FENG Ji-feng

    2015-01-01

    Objective:To explore the clinical efifcacy and safety of rituximab combined with chemotherapy and single chemotherapy for diffuse large B cell lymphoma (DLBCL). Methods:A total of 97 patients with DLBCL were selected. Patients treated by single chemotherapy were designed as control group, while those by rituximab combined with chemotherapy as observational group. All patients were treated for at least 4 cycles. The short-term and long-term efifcacy and related adverse reactions of 2 groups were observed. Results:The rate of complete remission (CR) in observational group was signiifcantly higher than in control group (χ2=4.6589,P=0.0309). However, there was no signiifcant difference in objective remission rate (ORR) between 2 groups (P=0.3651). The rates of 3-year overall survival (OS), progression-free survival (PFS) and disease-free survival (DFS) were 80.30% (53/66), 69.70% (46/66) and 59.09% (39/66) in observational group, and 61.29% (19/31), 58.06% (18/31) and 58.06% (18/31) in control group, respectively. The OS in observational group was signiifcantly longer than in control group (P=0.035). However, there was no signiifcant difference in PFS, DFS and rate adverse reactions between 2 groups (P=0.089;P=0.438;χ2=0.1562,P=0.6927). Conclusion: Rituximab combined with chemotherapy can improve the efficacy of DLBCL without increasing the adverse reactions, which can be used as the ifrst-line treatment for DLBCL, thus deserving to be widely applied in clinic.

  1. Prognostic value of tumor necrosis at CT in diffuse large B-cell lymphoma

    International Nuclear Information System (INIS)

    Highlights: •CT is compulsory for staging newly diagnosed DLBCL. •Approximately 13.7% of DLBCL patients have tumor necrosis at CT. •Tumor necrosis status at CT is not associated with any NCCN-IPI factor. •Patients with tumor necrosis at CT have a significantly worse outcome. -- Abstract: Objective: To determine the prognostic value of tumor necrosis at computed tomography (CT) in newly diagnosed diffuse large B-cell lymphoma (DLBCL). Materials and methods: This retrospective study included 51 patients with newly diagnosed DLBCL who had undergone both unenhanced and intravenous contrast-enhanced CT before R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin and prednisolone) chemo-immunotherapy. Presence of tumor necrosis was visually and quantitatively assessed at CT. Associations between tumor necrosis status at CT and the National Comprehensive Cancer Network (NCCN) International Prognostic Index (IPI) factors were assessed. Cox regression analysis was used to determine the prognostic impact of NCCN-IPI scores and tumor necrosis status at CT. Results: There were no correlations between tumor necrosis status at CT and the NCCN-IPI factors categorized age (ρ = −0.042, P = 0.765), categorized lactate dehydrogenase (LDH) ratio (ρ = 0.201, P = 0.156), extranodal disease in major organs (φ = −0.245, P = 0.083), Ann Arbor stage III/IV disease (φ = −0.208, P = 0.141), and Eastern Cooperative Oncology Group (ECOG) performance status (φ = 0.015, P = 0.914). In the multivariate Cox proportional hazards model, only tumor necrosis status at CT was an independent predictive factor of progression-free survival (P = 0.003) and overall survival (P = 0.004). Conclusion: The findings of this study indicate the prognostic potential of tumor necrosis at CT in newly diagnosed DLBCL

  2. Sarcopenia is an independent prognostic factor in male patients with diffuse large B-cell lymphoma.

    Science.gov (United States)

    Nakamura, Nobuhiko; Hara, Takeshi; Shibata, Yuhei; Matsumoto, Takuro; Nakamura, Hiroshi; Ninomiya, Soranobu; Kito, Yusuke; Kitagawa, Junichi; Kanemura, Nobuhiro; Goto, Naoe; Shiraki, Makoto; Miyazaki, Tatsuhiko; Takeuchi, Tamotsu; Shimizu, Masahito; Tsurumi, Hisashi

    2015-12-01

    Sarcopenia reportedly predicts poor outcomes in elderly patients with diffuse large B-cell lymphoma (DLBCL). However, because previous studies only involved elderly patients, it is difficult to generalize these results to all patients with DLBCL. We retrospectively analyzed 207 patients with DLBCL who received the R-CHOP or R-THP-COP regimen between June 2004 and May 2014. Sarcopenia was measured by the analysis of CT images at the L3 level before treatment. The surface of muscular tissues was selected according to the CT Hounsfield unit. This value was normalized for stature in order to calculate the L3 skeletal muscle index (L3 SMI, cm(2)/m(2)). Median age at diagnosis in the 121 males and 86 females was 67 years (range, 19-86 years). The sex-specific cutoffs for the L3 SMI were determined by receiver operator curve (ROC) analysis. Sarcopenic patients were older than non-sarcopenic patients, with a median age of 70 and 65 years, respectively (p sarcopenic and non-sarcopenic patients. With a median follow-up of 50.4 months, the 3-year overall survival (OS) was 70 % in the sarcopenic group and 85 % in the non-sarcopenic group (p = 0.0260). In a subgroup analysis by gender, there was a significant difference in the OS when comparing sarcopenic and non-sarcopenic patients in males but not in females (p = 0.0003, p = 0.4440, respectively). Sarcopenia is an independent prognostic factor in male patients with DLBCL. PMID:26385388

  3. CD52 expression in T-cell large granular lymphocyte leukemia--implications for treatment with alemtuzumab.

    Science.gov (United States)

    Osuji, N; Del Giudice, I; Matutes, E; Morilla, A; Owusu-Ankomah, K; Morilla, R; Dunlop, A; Catovksy, D

    2005-05-01

    Few reports on the successful treatment of T-cell large granular lymphocyte (LGL) leukemia with the humanized anti-CD52 monoclonal antibody alemtuzumab are emerging in the literature. The expression of CD52 by LGLs has not been previously investigated. Using semi-quantitative 2- and 3-color flow cytometry, we documented the expression of CD52 in 100% of abnormal cells in T-cell LGL leukemia (n = 11) and natural killer (NK) cell LGL leukemia (n = 2), and showed no significant difference in CD52 expression between T-cell prolymphocytic leukemia (PLL) and T-cell LGL leukemia. Higher CD52 expression has been noted in responders to alemtuzumab in T-cell PLL and in chronic lymphocytic leukemia (CLL), a B-cell disorder. The strong and consistent expression of CD52 shown here highlights the potential role of alemtuzumab in the treatment of refractory T-cell LGL leukemia and possibly aggressive NK cell leukemia. PMID:16019510

  4. Targeted agents in non-small cell lung cancer therapy: What is there on the horizon?

    Directory of Open Access Journals (Sweden)

    Victoria M Villaflor

    2013-01-01

    Full Text Available Lung cancer is a heterogeneous group of diseases. There has been much research in lung cancer over the past decade which has advanced our ability to treat these patients with a more personalized approach. The scope of this paper is to review the literature and give a broad understanding of the current molecular targets for which we currently have therapies as well as other targets for which we may soon have therapies. Additionally, we will cover some of the issues of resistance with these targeted therapies. The molecular targets we intend to discuss are epidermal growth factor receptor (EGFR, Vascular endothelial growth factor (VEGF, anaplastic large-cell lymphoma kinase (ALK, KRAS, C-MET/RON, PIK3CA. ROS-1, RET Fibroblast growth factor receptor (FGFR. Ephrins and their receptors, BRAF, and immunotherapies/vaccines. This manuscript only summarizes the work which has been done to date and in no way is meant to be comprehensive.

  5. A new method to address unmet needs for extracting individual cell migration features from a large number of cells embedded in 3D volumes.

    Directory of Open Access Journals (Sweden)

    Ivan Adanja

    Full Text Available BACKGROUND: In vitro cell observation has been widely used by biologists and pharmacologists for screening molecule-induced effects on cancer cells. Computer-assisted time-lapse microscopy enables automated live cell imaging in vitro, enabling cell behavior characterization through image analysis, in particular regarding cell migration. In this context, 3D cell assays in transparent matrix gels have been developed to provide more realistic in vitro 3D environments for monitoring cell migration (fundamentally different from cell motility behavior observed in 2D, which is related to the spread of cancer and metastases. METHODOLOGY/PRINCIPAL FINDINGS: In this paper we propose an improved automated tracking method that is designed to robustly and individually follow a large number of unlabeled cells observed under phase-contrast microscopy in 3D gels. The method automatically detects and tracks individual cells across a sequence of acquired volumes, using a template matching filtering method that in turn allows for robust detection and mean-shift tracking. The robustness of the method results from detecting and managing the cases where two cell (mean-shift trackers converge to the same point. The resulting trajectories quantify cell migration through statistical analysis of 3D trajectory descriptors. We manually validated the method and observed efficient cell detection and a low tracking error rate (6%. We also applied the method in a real biological experiment where the pro-migratory effects of hyaluronic acid (HA were analyzed on brain cancer cells. Using collagen gels with increased HA proportions, we were able to evidence a dose-response effect on cell migration abilities. CONCLUSIONS/SIGNIFICANCE: The developed method enables biomedical researchers to automatically and robustly quantify the pro- or anti-migratory effects of different experimental conditions on unlabeled cell cultures in a 3D environment.

  6. Large bowel obstruction resulting from bladder transitional cell carcinoma metastasis: a common cancer presenting in an uncommon manner.

    Science.gov (United States)

    Rohloff, Matthew; VandenBerg, Todd; MacMath, Terry

    2015-01-01

    Transitional cell carcinoma (TCC) and large bowel obstructions are both common disease processes typically considered unrelated. Presented below is the case of a 49-year-old male with a large bowel obstruction caused by a bladder TCC metastasis. One year prior to large bowel obstruction presentation, the patient had a T2, Grade III TCC of the bladder with no nodal involvement or metastasis, which was removed via radical cystoprostatectomy. This case serves as a reminder that cancer, despite common pathogenesis patterns, can present in atypical ways. PMID:26197806

  7. Large-scale prospective T cell function assays in shipped, unfrozen blood samples

    DEFF Research Database (Denmark)

    Hadley, David; Cheung, Roy K; Becker, Dorothy J;

    2014-01-01

    cell immunocompetence. We have found that the vast majority of the samples were viable up to 3 days from the blood draw, yet meaningful responses were found in a proportion of those with longer travel times. Furthermore, the shipping time of uncooled samples significantly decreased both the viabilities...... of the samples and the unstimulated cell counts in the viable samples. Also, subject age was significantly associated with the number of unstimulated cells and T cell proliferation to positive activators. Finally, we observed a pattern of statistically significant increases in T cell responses to...

  8. Observation of single neutral atoms in a large-magnetic-gradient vapour-cell magneto-optical trap

    Institute of Scientific and Technical Information of China (English)

    Wang Jing; He Jun; Qiu Ying; Yang Bao-Dong; Zhao Jiang-Yan; Zhang Tian-Cai; Wang Jun-Min

    2008-01-01

    Single caesium atoms in a large-magnetic-gradient vapour-cell magneto-optical trap have been identified. The trapping of individual atoms is marked by the steps in fluorescence signal corresponding to the capture or loss of single atoms. The typical magnetic gradient is about 29 mT/cm, which evidently reduces the capture rate of magneto-optical trap.

  9. Efficacy and Tolerability of Anthracycline-Based Therapy in Elderly Patients With Diffuse Large B-Cell Lymphoma

    OpenAIRE

    Davis, Christine C.; Cohen, Jonathon B.; Shah, Katherine S.; Hutcherson, Don A.; Surati, Minal J.; Valla, Kelly; Panjic, Elyse H.; Handler, Caitlin E.; Switchenko, Jeffrey M.; Flowers, Christopher R.

    2014-01-01

    We examined treatment with or without anthracyclines in 72 eldery diffuse large B-cell lymphoma patients (age ≥ 65 years) in a retrospective cohort analysis. Factors leading to treatment without an anthracycline included age and ejection fraction, whereas markers of tolerability were similar between groups. This study highlights the details of anthracycline tolerability in elderly lymphoma patients.

  10. Investigation of MGMT and DAPK1 methylation patterns in diffuse large B-cell lymphoma using allelic MSP-pyrosequencing

    DEFF Research Database (Denmark)

    Kristensen, Lasse Sommer; Treppendahl, Marianne Bach; Asmar, Fazila;

    2013-01-01

    The tumor suppressor genes MGMT and DAPK1 become methylated in several cancers including diffuse large B-cell lymphoma (DLBCL). However, allelic methylation patterns have not been investigated in DLBCL. We developed a fast and cost-efficient method for the analysis of allelic methylation based on...

  11. All polymer photovoltaics: From small inverted devices to large roll-to-roll coated and printed solar cells

    DEFF Research Database (Denmark)

    Liu, Yao; Larsen-Olsen, Thue Trofod; Zhao, Xingang; Andreasen, Birgitta; Søndergaard, Roar R.; Helgesen, Martin; Norrman, Kion; Jørgensen, Mikkel; Krebs, Frederik C; Zhan, Xiaowei

    2013-01-01

    Inverted all polymer solar cells based on a blend of a perylene diimide based polymer acceptor and a dithienosilole based polymer donor were fabricated from small area devices to roll-to-roll (R2R) coated and printed large area modules. The device performance was successfully optimized by using...

  12. A round robin study of flexible large-area roll-to-roll processed polymer solar cell modules

    DEFF Research Database (Denmark)

    Krebs, Frederik C; Gevorgyan, Suren; Gholamkhass, Bobak;

    2009-01-01

    A round robin for the performance of roll-to-roll coated flexible large-area polymer solar-cell modules involving 18 different laboratories in Northern America, Europe and Middle East is presented. The study involved the performance measurement of the devices at one location (Risø DTU) followed b...

  13. Novel lymphoid neoplasms – the borderland between diffuse large B-cell lymphoma and Burkitt’s lymphoma

    OpenAIRE

    de Jong, Daphne

    2009-01-01

    The recent update of the WHO classification of tumors of the lymphoid tissue has recognized a category with overlapping features between Burkitt lymphoma and diffuse large B-cell lymphoma. In this perspective article, Dr. de Jong reviews the conceptual basis and practical impact of this diagnosis. See related paper on page 935.

  14. Clinicopathological characteristics and prognostic analysis of 92 cases with primary gastrointestinal diffuse large B-cell lymphoma

    Institute of Scientific and Technical Information of China (English)

    冯佳

    2014-01-01

    Objective To analyze the clinical and pathological features,molecular biological markers and prognosis of primary gastrointestinal diffuse large B-cell lymphoma(DLBCL).Methods A retrospective study was conducted in 92 cases of primary gastrointestinal DLBCL.The data of clinical characteristics,pathological and immunohistochemical features were analyzed.The relationship between different factors at diagnosis and prognosis were

  15. Tumor necrosis at FDG-PET is an independent predictor of outcome in diffuse large B-cell lymphoma

    NARCIS (Netherlands)

    Adams, Hugo J A; De Klerk, John M H; Fijnheer, Rob; Heggelman, Ben G F; Dubois, Stefan V.; Nievelstein, Rutger A J; Kwee, Thomas C.

    2016-01-01

    Purpose To determine the prognostic performance of tumor necrosis at FDG-PET in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) who are treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. Materials and methods 108 patients with new

  16. Mutational and structural analysis of diffuse large B-cell lymphoma using whole genome sequencing | Office of Cancer Genomics

    Science.gov (United States)

    Abstract: Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous cancer comprising at least two molecular subtypes that differ in gene expression and distribution of mutations. Recently, application of genome/exome sequencing and RNA-seq to DLBCL has revealed numerous genes that are recurrent targets of somatic point mutation in this disease.

  17. MicroRNAs as novel biomarkers in diffuse large B-cell lymphoma--a systematic review

    DEFF Research Database (Denmark)

    Jørgensen, Laura Krogh; Poulsen, Mette Østergaard; Laursen, Maria Bach; Marques, Sara Correia; Johnsen, Hans E; Bøgsted, Martin; Dybkær, Karen

    2014-01-01

    INTRODUCTION: MicroRNAs (miRNAs) are short non-coding RNAs that have the ability to regulate gene expression at the post-transcriptional level. MiRNAs are deregulated in many cancer types, and several miRNAs have been suggested as novel diagnostic and prognostic biomarkers in diffuse large B-cell...

  18. Data Mining on Survival Prediction after Chemotherapy for Diffuse Large-B-Cell Lymphoma and Genomics of Metastasis Cancer

    Directory of Open Access Journals (Sweden)

    Shen Lu

    2014-12-01

    Full Text Available This research pertains to the applications of data mining of microarray databases for large-B-cell Lymphoma and metastasis cancer, the latter of which little has been known about the genomic events that regulate the transformation of a tumor into a metastatic phenotype.

  19. Unusual presentation of high-grade neuroendocrine carcinoma of the Urinary bladder with small-cell and large-cell features

    OpenAIRE

    Vitor Fiorin de Vasconcellos; João Lapa Lima Trancoso; Aloísio Felipe-Silva; Angélica Braz Simões; Pedro José dos Santos Neto; Oscar Eduardo Hidetoshi Fugita; Carla Rachel Ono; Carlos Alberto Buchpiguel

    2013-01-01

    High-grade neuroendocrine carcinoma of the urinary bladder comprehends small-cell and large-cell variants. It is a rare and aggressive neoplasm, mostly diagnosed in advanced stages. It is more frequently encountered among Caucasian men in the sixth decade of life. Urinary symptoms are the most common clinical presentation. Diagnosis is generally not troublesome once the lesions are easily detectable by imaging exams and cystoscopy. This neoplasia is associated with tobacco smoking, and is fre...

  20. 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