WorldWideScience

Sample records for ebv-positive diffuse large

  1. EBV-positive diffuse large B-cell lymphoma of the elderly

    NARCIS (Netherlands)

    C.Y. Ok (Chi Young); T.G. Papathomas (Thomas); L.J. Medeiros (L. Jeffrey); K.H. Young (Ken)

    2013-01-01

    textabstractEpstein-Barr virus (EBV) positive diffuse large B-cell lymphoma (DLBCL) of the elderly, initially described in 2003, is a provisional entity in the 2008World Health Organization classification system and is defined as an EBV-positive monoclonal large B-cell proliferation that occurs in

  2. EBV-positive diffuse large B-cell lymphoma in young adults: is this a distinct disease entity?

    Science.gov (United States)

    Hong, J Y; Yoon, D H; Suh, C; Huh, J; Do, I-G; Sohn, I; Jo, J; Jung, S-H; Hong, M E; Yoon, H; Ko, Y H; Kim, S J; Kim, W S

    2015-03-01

    Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) of the elderly is defined only in adults older than 50 years. However, EBV-positive DLBCL can affect younger patients. We investigated the prevalence, clinical characteristics and survival outcomes of EBV-positive DLBCL in young adults. We analyzed patients with de novo DLBCL who were registered in the Samsung Medical Center (SMC) retrospective lymphoma cohort and prospective SMC Lymphoma Cohort Study I (ClinicalTrials.gov: NCT00822731). A total of 571 cases were included in the analysis. The prevalence of EBV positivity was 6.7% (13/195) and 9.3% (35/376) in the young group (≤50 years) and in the elderly group (>50 years), respectively. EBV status was closely associated with unique unfavorable clinical characteristics [older age, more advanced stage, two or more sites of extranodal involvement, higher International Prognostic Index (IPI), and age-adjusted IPI risk] only in the elderly group. Poor prognostic impact of EBV positivity on overall survival was observed only in the elderly group [hazard ratio (HR) 2.86; 95% confidence interval (CI) 1.83-4.47; P young group (HR 1.17; 95% CI 0.35-3.89; P = 0.801). A substantial proportion of EBV-positive DLBCL of the elderly can occur in young adults. EBV positivity of DLBCL in young adults was not associated with unfavorable clinical characteristics or worse outcomes. We suggest that EBV-positive DLBCL should not be confined only in the elderly and 'EBV-positive DLBCL in young adults' needs to be considered as a clinically distinct disease entity. ClinicalTrials.gov: NCT02060435. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  3. Reappraisal of Epstein-Barr virus (EBV) in diffuse large B-cell lymphoma (DLBCL): comparative analysis between EBV-positive and EBV-negative DLBCL with EBV-positive bystander cells.

    Science.gov (United States)

    Ohashi, Akiko; Kato, Seiichi; Okamoto, Akinao; Inaguma, Yoko; Satou, Akira; Tsuzuki, Toyonori; Emi, Nobuhiko; Okamoto, Masataka; Nakamura, Shigeo

    2017-07-01

    Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) not otherwise specified is defined as monoclonal EBV+ B-cell proliferation affecting patients without any known immunosuppression. Non-neoplastic EBV+ cells proliferating in or adjacent to EBV- DLBCL were reported recently, but their clinical significance is unclear. Thus, the aim of this study was to investigate the prognostic impact of EBV+ cells in DLBCL. We compared the clinicopathological characteristics of 30 EBV+ DLBCL patients and 29 and 604 EBV- DLBCL patients with and without EBV+ bystander cells (median age of onset 71, 67 and 62 years, respectively). Both EBV+ DLBCL patients and EBV- DLBCL patients with EBV+ bystander cells tended to have high and high-intermediate International Prognostic Index scores (60% and 59%, respectively), as compared with only 46% of EBV- DLBCL patients without EBV+ bystander cells. EBV- DLBCL patients with EBV+ bystander cells showed a significantly higher incidence of lung involvement than those without EBV+ bystander cells (10% versus 2%, P bystander cells had a poorer prognosis than patients without any detectable EBV+ cells [median overall survival (OS) of 100 months and 40 months versus not reached, P bystander cells treated with rituximab showed overlapping survival curves (OS, P = 0.77; progression-free survival, P = 1.0). EBV- DLBCL with bystander EBV+ cells has similar clinical characteristics to EBV+ DLBCL. DLBCL with EBV+ bystander cells may be related to both age-related and microenvironment-related immunological deterioration. © 2017 John Wiley & Sons Ltd.

  4. EBV Positive Diffuse Large B Cell Lymphoma and Chronic Lymphocytic Leukemia Patients Exhibit Increased Anti-dUTPase Antibodies

    Directory of Open Access Journals (Sweden)

    Marshall Williams

    2018-05-01

    Full Text Available The Epstein-Barr virus (EBV, which is a ubiquitous γ-herpesvirus, establishes a latent infection in more than 90% of the global adult population. EBV-associated malignancies have increased by 14.6% over the last 20 years, and account for approximately 1.5% of all cancers worldwide and 1.8% of all cancer deaths. However, the potential involvement/contribution of lytic proteins to the pathophysiology of EBV-associated cancers is not well understood. We have previously demonstrated that the EBV-deoxyuridine triphosphate nucleotidohydrolase (dUTPase modulates innate and adaptive immune responses by engaging the Toll-Like Receptor 2 (TLR2, which leads to the modulation of downstream genes involved in oncogenesis, chronic inflammation, and in effector T-cell function. Furthermore, examination of serum samples from diffuse large B-cell lymphoma (DLBCL and chronic lymphocytic leukemia patients revealed the presence of increased levels of anti-dUTPase antibodies in both cohorts compared to controls with the highest levels (3.67-fold increase observed in DLBCL female cases and the lowest (2.12-fold increase in DLBCL males. Using computer-generated algorithms, dUTPase amino acid sequence alignments, and functional studies of BLLF3 mutants, we identified a putative amino acid motif involved with TLR2 interaction. These findings suggest that the EBV-dUTPase: TLR2 interaction is a potential molecular target that could be used for developing novel therapeutics (small molecules/vaccines.

  5. The presence of Epstein-Barr virus (EBV) in diffuse large B-cell lymphomas (DLBCLs) in Turkey: special emphasis on 'EBV-positive DLBCL of the elderly'.

    Science.gov (United States)

    Uner, Aysegul; Akyurek, Nalan; Saglam, Arzu; Abdullazade, Samir; Uzum, Nuket; Onder, Sevgen; Barista, Ibrahim; Benekli, Mustafa

    2011-04-01

    Accumulated evidence has shown the importance of Epstein-Barr virus in the pathogenesis of various lymphomas. This study aimed to determine the prevalence of Epstein-Barr virus expression and its effect on survival amongst diffuse large B-cell lymphoma (DLBCL) cases from two large tertiary care centres in Turkey with a particular interest in identifying cases of 'Epstein-Barr virus-positive DLBCL of the elderly'. Diffuse large B-cell lymphoma cases diagnosed between 1999 and 2009 were retrieved and 340 cases were used to construct tissue microarrays. The presence of Epstein-Barr virus small ribonucleic acids was examined by in situ hybridization using Epstein-Barr virus (EBV)-encoded small RNA (EBER) oligonucleotides. A total of 18 cases (5.3%) showed Epstein-Barr virus expression. Twelve cases were classified as Epstein-Barr virus-positive DLBCL of the elderly. Epstein-Barr virus-positive DLBCL cases showed a significantly inferior overall survival as compared with Epstein-Barr virus-negative cases (p < 0.001). In our study group Epstein-Barr virus expression is not prevalent in DLBCLs. Epstein-Barr virus-positive DLBCL of the elderly is also rare in the Turkish population. The presence of Epstein-Barr virus, however, is associated with poor prognosis. © 2011 The Authors. APMIS © 2011 APMIS.

  6. EBV-positive diffuse large B-cell lymphoma in a patient with primary Sjögren’s syndrome and membranous glomerulonephritis

    Directory of Open Access Journals (Sweden)

    Kim Chang

    2012-11-01

    Full Text Available Abstract Background Sjögren’s syndrome is a systemic autoimmune disease in which lymphatic cells destroy the salivary and lacrimal glands. Glomerulonephritis is thought to be a rare occurrence in primary Sjögren’s syndrome. Furthermore, concurrent glomerular involvement and lymphoma in patients with Sjögren’s syndrome has seldom been reported. Case presentation A 52-year-old woman with primary Sjögren’s syndrome developed membranous glomerulonephritis and Epstein-Barr virus-positive diffuse large B-cell lymphoma (DLBCL. She was diagnosed with Sjögren’s syndrome based on the dry eyes, dry mouth, positive anti-nuclear antibody test, anti-Ro (SS-A antibody, salivary gland biopsy, and salivary scintigraphy. Moreover, renal biopsy confirmed the diagnosis of membranous glomerulonephritis. Three months later, her small bowel was perforated with pneumoperitoneum, and the biopsy revealed Epstein-Barr virus-positive DLBCL. Conclusions We observed the first case of primary Sjögren’s syndrome associated with Epstein-Barr Virus-positive DLBCL and membranous glomerulonephritis. Because of the possibility of malignancy-associated membranous glomerulonephritis in patients with primary Sjögren’s syndrome, we should be careful and examine such patients for hidden malignancy.

  7. Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma in the Elderly: A Matched Case-Control Analysis.

    Directory of Open Access Journals (Sweden)

    Chen-Ge Song

    Full Text Available Epstein-Barr virus (EBV-positive diffuse large B-cell lymphoma (DLBCL in the elderly has rarely been reported. This study aimed to explore the clinical characteristics and prognosis of this entity.In situ hybridization (ISH analysis of Epstein-Barr virus (EBV and immunohistochemistry was performed in 230 tumor specimens from consecutive de novo DLBCL patients over 50 years old. A matched-case control analysis (1:3 was utilized to compare EBV-positive and EBV-negative DLBCL in the elderly.A total of 16 patients (7.0% were diagnosed with EBV-positive DLBCL. Of these 16 cases, the median age was 62 years, with a male to female ratio of 11:5. Elderly EBV-positive DLBCL patients had a higher incidence of non-germinal center B-cell (non-GCB subtypes (87.5% and high Ki67 (75% and CD30 expression (93.8%. For EBV-positive patients undergoing initial chemotherapy, 7 of 16 (43.8% had complete remission, 2 (12.5% had partial remission, 2 (12.5% had stable disease, and 5 (31.3% had progressive disease. The median overall survival was 9 months for the EBV-positive patients. A matched-case control analysis suggested that EBV-positive patients had inferior survival outcomes compared with EBV-negative patients (3-year progression-free survival [PFS]: 25% vs. 76.7%, respectively; 3-year overall survival [OS]: 25% vs. 77.4%, respectively; P<0.001.EBV-positive DLBCL of the elderly is associated with an inferior clinical course and inferior survival outcomes. The role of EBV in this disease and the optimal management of this subgroup warrants further investigation.

  8. Frequent downregulation of BTB and CNC homology 2 expression in Epstein-Barr virus-positive diffuse large B-cell lymphoma.

    Science.gov (United States)

    Noujima-Harada, Mai; Takata, Katsuyoshi; Miyata-Takata, Tomoko; Sakurai, Hiroaki; Igarashi, Kazuhiko; Ito, Etsuro; Nagakita, Keina; Taniguchi, Kohei; Ohnishi, Nobuhiko; Omote, Shizuma; Tabata, Tetsuya; Sato, Yasuharu; Yoshino, Tadashi

    2017-05-01

    Diffuse large B-cell lymphoma (DLBCL) is the most common B-cell lymphoma subtype, and the Epstein-Barr virus (EBV)-positive subtype of DLBCL is known to show a more aggressive clinical behavior than the EBV-negative one. BTB and CNC homology 2 (BACH2) has been highlighted as a tumor suppressor in hematopoietic malignancies; however, the role of BACH2 in EBV-positive DLBCL is unclear. In the present study, BACH2 expression and its significance were studied in 23 EBV-positive and 43 EBV-negative patient samples. Immunohistochemistry revealed BACH2 downregulation in EBV-positive cases (P < 0.0001), although biallelic deletion of BACH2 was not detected by FISH. Next, we analyzed the contribution of BACH2 negativity to aggressiveness in EBV-positive B-cell lymphomas using FL-18 (EBV-negative) and FL-18-EB cells (FL-18 sister cell line, EBV-positive). In BACH2-transfected FL-18-EB cells, downregulation of phosphorylated transforming growth factor-β-activated kinase 1 (pTAK1) and suppression in p65 nuclear fractions were observed by Western blot analysis contrary to non-transfected FL-18-EB cells. In patient samples, pTAK1 expression and significant nuclear p65, p50, and p52 localization were detected immunohistochemically in BACH2-negative DLBCL (P < 0.0001, P = 0.006, and P = 0.001, respectively), suggesting that BACH2 downregulation contributes to constitutive activation of the nuclear factor-κB pathway through TAK1 phosphorylation in BACH2-negative DLBCL (most EBV-positive cases). Although further molecular and pathological studies are warranted to clarify the detailed mechanisms, downregulation of BACH2 may contribute to constitutive activation of the nuclear factor-κB pathway through TAK1 activation. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  9. Synchronous Microscopic Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma of the Adrenal and Lymphoplasmacytic Lymphoma: De Novo Disease or Transformation?

    Science.gov (United States)

    Moonim, Mufaddal T; Nasir, Alia; Hubbard, Jonathan; Ketley, Nicholas; Fields, Paul

    2017-06-01

    Lymphomas arising in the adrenal are rare, and to our knowledge, 2 cases of Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphomas (DLBCL) in an adrenal pseudocyst have been reported. We report an incidental EBV-positive DLBCL arising in an adrenal pseudocyst in a 58-year-old man with a 7-year history of lymphoplasmacytic lymphoma (LPL). The DLBCL was present in the fibrinous exudate, while the LPL resided in the cyst wall. The patient underwent de-roofing of the same cyst 3 years previously; review of histology revealed foci of LPL in the cyst wall, but not of DLBCL. There have been reports of similar microscopic EBV-positive DLBCLs within enclosed cystic spaces. However, all these cases were incidental extranodal primary DLBCLs. Since residual LPL was present alongside DLBCL, with similar light chain restriction, we propose that this may represent transformation, rather than a de novo primary EBV-driven lymphoma.

  10. Immune Activation and Benefit From Avelumab in EBV-Positive Gastric Cancer.

    Science.gov (United States)

    Panda, Anshuman; Mehnert, Janice M; Hirshfield, Kim M; Riedlinger, Greg; Damare, Sherri; Saunders, Tracie; Kane, Michael; Sokol, Levi; Stein, Mark N; Poplin, Elizabeth; Rodriguez-Rodriguez, Lorna; Silk, Ann W; Aisner, Joseph; Chan, Nancy; Malhotra, Jyoti; Frankel, Melissa; Kaufman, Howard L; Ali, Siraj; Ross, Jeffrey S; White, Eileen P; Bhanot, Gyan; Ganesan, Shridar

    2018-03-01

    Response to immune checkpoint therapy can be associated with a high mutation burden, but other mechanisms are also likely to be important. We identified a patient with metastatic gastric cancer with meaningful clinical benefit from treatment with the anti-programmed death-ligand 1 (PD-L1) antibody avelumab. This tumor showed no evidence of high mutation burden or mismatch repair defect but was strongly positive for presence of Epstein-Barr virus (EBV) encoded RNA. Analysis of The Cancer Genome Atlas gastric cancer data (25 EBV+, 80 microsatellite-instable [MSI], 310 microsatellite-stable [MSS]) showed that EBV-positive tumors were MSS. Two-sided Wilcoxon rank-sum tests showed that: 1) EBV-positive tumors had low mutation burden (median = 2.07 vs 3.13 in log10 scale, P < 10-12) but stronger evidence of immune infiltration (median ImmuneScore 2212 vs 1295, P < 10-4; log2 fold-change of CD8A = 1.85, P < 10-6) compared with MSI tumors, and 2) EBV-positive tumors had higher expression of immune checkpoint pathway (PD-1, CTLA-4 pathway) genes in RNA-seq data (log2 fold-changes: PD-1 = 1.85, PD-L1 = 1.93, PD-L2 = 1.50, CTLA-4 = 1.31, CD80 = 0.89, CD86 = 1.31, P < 10-4 each), and higher lymphocytic infiltration by histology (median tumor-infiltrating lymphocyte score = 3 vs 2, P < .001) compared with MSS tumors. These data suggest that EBV-positive low-mutation burden gastric cancers are a subset of MSS gastric cancers that may respond to immune checkpoint therapy.

  11. EBV induces persistent NF-κB activation and contributes to survival of EBV-positive neoplastic T- or NK-cells.

    Directory of Open Access Journals (Sweden)

    Honami Takada

    Full Text Available Epstein-Barr virus (EBV has been detected in several T- and NK-cell neoplasms such as extranodal NK/T-cell lymphoma nasal type, aggressive NK-cell leukemia, EBV-positive peripheral T-cell lymphoma, systemic EBV-positive T-cell lymphoma of childhood, and chronic active EBV infection (CAEBV. However, how this virus contributes to lymphomagenesis in T or NK cells remains largely unknown. Here, we examined NF-κB activation in EBV-positive T or NK cell lines, SNT8, SNT15, SNT16, SNK6, and primary EBV-positive and clonally proliferating T/NK cells obtained from the peripheral blood of patients with CAEBV. Western blotting, electrophoretic mobility shift assays, and immunofluorescent staining revealed persistent NF-κB activation in EBV-infected cell lines and primary cells from patients. Furthermore, we investigated the role of EBV in infected T cells. We performed an in vitro infection assay using MOLT4 cells infected with EBV. The infection directly induced NF-κB activation, promoted survival, and inhibited etoposide-induced apoptosis in MOLT4 cells. The luciferase assay suggested that LMP1 mediated NF-κB activation in MOLT4 cells. IMD-0354, a specific inhibitor of NF-κB that suppresses NF-κB activation in cell lines, inhibited cell survival and induced apoptosis. These results indicate that EBV induces NF-κB-mediated survival signals in T and NK cells, and therefore, may contribute to the lymphomagenesis of these cells.

  12. Epstein-Barr virus (EBV) provides survival factors to EBV+ diffuse large B-cell lymphoma (DLBCL) lines and modulates cytokine induced specific chemotaxis in EBV+  DLBCL.

    Science.gov (United States)

    Wu, Liang; Ehlin-Henriksson, Barbro; Zhou, Xiaoying; Zhu, Hong; Ernberg, Ingemar; Kis, Lorand L; Klein, George

    2017-12-01

    Diffuse large B-cell lymphoma (DLBCL), the most common type of malignant lymphoma, accounts for 30% of adult non-Hodgkin lymphomas. Epstein-Barr virus (EBV) -positive DLBCL of the elderly is a newly recognized subtype that accounts for 8-10% of DLBCLs in Asian countries, but is less common in Western populations. Five DLBCL-derived cell lines were employed to characterize patterns of EBV latent gene expression, as well as response to cytokines and chemotaxis. Interleukin-4 and interleukin-21 modified LMP1, EBNA1 and EBNA2 expression depending on cell phenotype and type of EBV latent programme (type I, II or III). These cytokines also affected CXCR4- or CCR7-mediated chemotaxis in two of the cell lines, Farage (type III) and Val (type II). Further, we investigated the effect of EBV by using dominant-negative EBV nuclear antigen 1(dnEBNA1) to eliminate EBV genomes. This resulted in decreased chemotaxis. By employing an alternative way to eliminate EBV genomes, Roscovitine, we show an increase of apoptosis in the EBV-positive lines. These results show that EBV plays an important role in EBV-positive DLBCL lines with regard to survival and chemotactic response. Our findings provide evidence for the impact of microenvironment on EBV-carrying DLBCL cells and might have therapeutic implications. © 2017 John Wiley & Sons Ltd.

  13. B cell differentiation in EBV-positive Burkitt Lymphoma is impaired at post-transcriptional level by miRNA altered expression

    DEFF Research Database (Denmark)

    Leucci, E; Onnis, A; Cocco, M

    2009-01-01

    suggested that EBV-positive and EBV-negative BL have different cells of origin. In particular, according to immunoglobulin gene mutation analysis, EBV-negative BLs may originate from early centroblasts, whereas EBV-positive BLs appear to arise from postgerminal center B cells or memory B cells...

  14. P-glycoprotein is expressed and causes resistance to chemotherapy in EBV-positive T-cell lymphoproliferative diseases

    International Nuclear Information System (INIS)

    Yoshimori, Mayumi; Takada, Honami; Imadome, Ken-Ichi; Kurata, Morito; Yamamoto, Kouhei; Koyama, Takatoshi; Shimizu, Norio; Fujiwara, Shigeyoshi; Miura, Osamu; Arai, Ayako

    2015-01-01

    Epstein–Barr virus-positive T-cell lymphoproliferative diseases (EBV-T-LPDs) are rare lymphomas with poor prognosis. Although chemotherapeutic strategies such as CHOP have been often selected, they have exhibited only limited efficacy. To clarify the mechanism of chemoresistance, we examined P-glycoprotein (P-gp) expression. P-gp acts as an energy-dependent efflux pump that excretes drugs from the cytoplasm, resulting in low-intracellular drug concentrations and poor sensitivity to chemotherapy. We examined P-gp expression in EBV-positive cells by immunohistochemistry staining in three patients of EBV-T-LPDs and the expression was detected in all patients. We also examined mdr1 mRNA expression by reverse-transcriptase polymerase-chain reaction (RT-PCR) in EBV-positive tumor cells from these patients and additional three patients. The expression was detected in all examined patients. In five EBV-T-LPDs patients, P-gp function was detected by Rhodamine-123 efflux assay in these cells. The efflux was inhibited by treatment with a P-gp inhibitor, cyclosporine A (CsA). We also examined and detected P-gp expression in EBV-positive T-cell lines SNT8 and SNT16 established from EBV-T-LPDs patients, by RT-PCR and western blotting. The function was also detected by Rhodamine-123 efflux in these cell lines. Inhibition and knock down of P-gp by CsA and siRNA, respectively, enhanced etoposide- and doxorubicin-induced cell death in the EBV-positive T-cell lines. Finally, we infected the T-cell line MOLT4 with EBV, and found that mdr1 mRNA expression and Rhodamine 123 efflux were upregulated after infection. These results indicated that enhanced P-gp expression contributed to the chemoresistance of EBV-T-LPDs

  15. Partial Least Squares Based Gene Expression Analysis in EBV- Positive and EBV-Negative Posttransplant Lymphoproliferative Disorders.

    Science.gov (United States)

    Wu, Sa; Zhang, Xin; Li, Zhi-Ming; Shi, Yan-Xia; Huang, Jia-Jia; Xia, Yi; Yang, Hang; Jiang, Wen-Qi

    2013-01-01

    Post-transplant lymphoproliferative disorder (PTLD) is a common complication of therapeutic immunosuppression after organ transplantation. Gene expression profile facilitates the identification of biological difference between Epstein-Barr virus (EBV) positive and negative PTLDs. Previous studies mainly implemented variance/regression analysis without considering unaccounted array specific factors. The aim of this study is to investigate the gene expression difference between EBV positive and negative PTLDs through partial least squares (PLS) based analysis. With a microarray data set from the Gene Expression Omnibus database, we performed PLS based analysis. We acquired 1188 differentially expressed genes. Pathway and Gene Ontology enrichment analysis identified significantly over-representation of dysregulated genes in immune response and cancer related biological processes. Network analysis identified three hub genes with degrees higher than 15, including CREBBP, ATXN1, and PML. Proteins encoded by CREBBP and PML have been reported to be interact with EBV before. Our findings shed light on expression distinction of EBV positive and negative PTLDs with the hope to offer theoretical support for future therapeutic study.

  16. Epstein-Barr virus-positive diffuse large B-cell lymphoma in children: a disease reminiscent of Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly.

    Science.gov (United States)

    Uccini, Stefania; Al-Jadiry, Mazin F; Scarpino, Stefania; Ferraro, Daniela; Alsaadawi, Adel R; Al-Darraji, Amir F; Moleti, Maria Luisa; Testi, Anna Maria; Al-Hadad, Salma A; Ruco, Luigi

    2015-05-01

    Pediatric Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (EBV+ DLBCL) is a rare disease in nonimmunocompromised hosts. In a review of 231 cases of malignant lymphoma (87 Hodgkin lymphoma and 144 non-Hodgkin lymphoma) occurring in Iraqi children, 7 cases (5% of NHLs) were classified as EBV+ DLBCL. Six children presented with nodal disease, and 1 presented with extranodal localization (bone). In all cases, the disease was at an advanced clinical stage (III/IV). Evidence of immunodeficiency (Evans syndrome and selective IgA deficiency) was observed in a single case. Two cases were "monomorphic" with immunoblastic histology, and 5 cases were "polymorphic" with histologic aspects reminiscent of nodular lymphocyte-predominant Hodgkin lymphoma (2 cases) and of CD30+ classical Hodgkin lymphoma (3 cases). In all cases, tumor cells were EBV infected (EBER+/LMP-1+), were medium-large B-cells (CD20+/CD79a+/PAX-5+/BOB-1+/OCT-2+) of non-germinal center (non-GC) origin (CD10-/MUM-1+), and had high proliferative activity (50%-70%). Chromosomal translocations involving BCL2, MYC, and IGH genes were not observed. IGH monoclonality could be demonstrated in 3 of 3 investigated cases. Six cases of EBV-negative DLBCL (4% of NHL) were present in the same series. All had monomorphic histology with centroblastic/immunoblastic morphology; 3 cases were of GC type and 3 of non-GC type. Our findings indicate that in Iraq, DLBCLs are 9% of NHLs. Moreover, 2 different types of the disease do exist; the EBV-positive cases, with strong histologic and immunohistochemical resemblance with EBV+ DLBCL of the elderly, and the EBV-negative cases, which are similar to the pediatric DLBCL usually observed in Western populations. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Atmospheric diffusion of large clouds

    Energy Technology Data Exchange (ETDEWEB)

    Crawford, T. V. [Univ. of California, Lawrence Radiation Lab., Livermore, California (United States)

    1967-07-01

    Clouds of pollutants travel within a coordinate system that is fixed to the earth's surface, and they diffuse and grow within a coordinate system fixed to the cloud's center. This paper discusses an approach to predicting the cloud's properties, within the latter coordinate system, on space scales of a few hundred meters to a few hundred kilometers and for time periods of a few days. A numerical cloud diffusion model is presented which starts with a cloud placed arbitrarily within the troposphere. Similarity theories of atmospheric turbulence are used to predict the horizontal diffusivity as a function of initial cloud size, turbulent atmospheric dissipation, and time. Vertical diffusivity is input as a function of time and height. Therefore, diurnal variations of turbulent diffusion in the boundary layer and effects of temperature inversions, etc. can be modeled. Nondiffusive cloud depletion mechanisms, such as dry deposition, washout, and radioactive decay, are also a part of this numerical model. An effluent cloud, produced by a reactor run at the Nuclear Rocket Development Station, Nevada, is discussed in this paper. Measurements on this cloud, for a period of two days, are compared to calculations with the above numerical cloud diffusion model. In general, there is agreement. within a factor of two, for airborne concentrations, cloud horizontal area, surface air concentrations, and dry deposition as airborne concentration decreased by seven orders of magnitude during the two-day period. (author)

  18. Determining the correlation of Epstein-Barr virus with diffuse large B-cell lymphoma by chromogenic in situ hybridization

    Directory of Open Access Journals (Sweden)

    Kosari F

    2012-09-01

    Full Text Available Background: Diffuse large B-cell lymphoma (DLBCL is the most common type of lymphoma. There are various types of DLBCL including immunoblastic and centroblastic. Epstein-Barr virus (EBV is a member of Herpes virus family found in all human populations inducing different lymphoproliferative disorders. The role of EBV in the development of DLBCL is known. Multiple laboratory methods are available for detecting EBV. This study was conducted to determine the correlation of EBV with DLBCL in samples referred to pathology ward in Shariati and Sina Hospitals by chromogenic in situ hybridization (CISH method.Methods: In this case/control study, pathological specimens of 50 patients with DLBCL as well as 50 reactive lymph nodes and tonsils (control group were collected from archives of Shariati and Sina Hospitals and were evaluated for EBV encoded RNA (EBER expression based on CISH method. A peptide nucleic acid (PNA EBV probe (Dakocytomatin was used while all the processes were done in RNAase-free conditions using RNAase-free water, sterile gloves and samplers. Results: Out of fifty specimens in the case group, eight were positive for EBER in comparison with two in the control group (P=0.046. No statistically significant difference was observed between intranodal or extranodal samples (P=0.736 or between males and females (P=0.0746.Conclusion: Our study showed that EBV positivity for EBER in patient with DLBCL could be determined more effectively by CISH method than immunohistochemistry (IHC. Comparative analysis between CISH, PCR and IHC methods is recommended.

  19. A recombinant modified vaccinia ankara vaccine encoding Epstein-Barr Virus (EBV) target antigens: a phase I trial in UK patients with EBV-positive cancer.

    Science.gov (United States)

    Taylor, Graham S; Jia, Hui; Harrington, Kevin; Lee, Lip Wai; Turner, James; Ladell, Kristin; Price, David A; Tanday, Manjit; Matthews, Jen; Roberts, Claudia; Edwards, Ceri; McGuigan, Lesley; Hartley, Andrew; Wilson, Steve; Hui, Edwin P; Chan, Anthony T C; Rickinson, Alan B; Steven, Neil M

    2014-10-01

    Epstein-Barr virus (EBV) is associated with several cancers in which the tumor cells express EBV antigens EBNA1 and LMP2. A therapeutic vaccine comprising a recombinant vaccinia virus, MVA-EL, was designed to boost immunity to these tumor antigens. A phase I trial was conducted to demonstrate the safety and immunogenicity of MVA-EL across a range of doses. Sixteen patients in the United Kingdom (UK) with EBV-positive nasopharyngeal carcinoma (NPC) received three intradermal vaccinations of MVA-EL at 3-weekly intervals at dose levels between 5 × 10(7) and 5 × 10(8) plaque-forming units (pfu). Blood samples were taken at screening, after each vaccine cycle, and during the post-vaccination period. T-cell responses were measured using IFNγ ELISpot assays with overlapping EBNA1/LMP2 peptide mixes or HLA-matched epitope peptides. Polychromatic flow cytometry was used to characterize functionally responsive T-cell populations. Vaccination was generally well tolerated. Immunity increased after vaccination to at least one antigen in 8 of 14 patients (7/14, EBNA1; 6/14, LMP2), including recognition of epitopes that vary between EBV strains associated with different ethnic groups. Immunophenotypic analysis revealed that vaccination induced differentiation and functional diversification of responsive T-cell populations specific for EBNA1 and LMP2 within the CD4 and CD8 compartments, respectively. MVA-EL is safe and immunogenic across diverse ethnicities and thus suitable for use in trials against different EBV-positive cancers globally as well as in South-East Asia where NPC is most common. The highest dose (5 × 10(8) pfu) is recommended for investigation in current phase IB and II trials. ©2014 American Association for Cancer Research.

  20. Diffuse reflectance relations based on diffusion dipole theory for large absorption and reduced scattering

    NARCIS (Netherlands)

    Bremmer, Rolf H.; van Gemert, Martin J. C.; Faber, Dirk J.; van Leeuwen, Ton G.; Aalders, Maurice C. G.

    2013-01-01

    Diffuse reflectance spectra are used to determine the optical properties of biological samples. In medicine and forensic science, the turbid objects under study often possess large absorption and/or scattering properties. However, data analysis is frequently based on the diffusion approximation to

  1. T-cell receptor (TCR) phenotype of nodal Epstein-Barr virus (EBV)-positive cytotoxic T-cell lymphoma (CTL): a clinicopathologic study of 39 cases.

    Science.gov (United States)

    Kato, Seiichi; Asano, Naoko; Miyata-Takata, Tomoko; Takata, Katsuyoshi; Elsayed, Ahmed Ali; Satou, Akira; Takahashi, Emiko; Kinoshita, Tomohiro; Nakamura, Shigeo

    2015-04-01

    Among Epstein-Barr virus (EBV)-positive cytotoxic T/NK-cell lymphoma, there are only a few reports on the clinicopathologic features of patients with primary nodal presentation (nodal EBV cytotoxic T-cell lymphoma [CTL]). Here, we compared the clinicopathologic profiles of 39 patients with nodal EBV CTL with those of 27 cases of "extranasal" NK/T-cell lymphoma of nasal type (ENKTL), especially addressing their T-cell receptor (TCR) phenotype. Histologically, 22 of 39 nodal EBV CTL cases (56%) were unique in having centroblastoid appearance, which was contrasted with the lower incidence of this feature in ENKTL (15%, P=0.001). In contrast, pleomorphic appearance was more frequently seen in ENKTL than in nodal EBV CTL (67% vs. 23%, P=0.001). Thirty-three of 39 nodal EBV CTL cases (85%) were of T-cell lineage on the basis of TCR expression and/or TCRγ gene rearrangement; in detail, 18 cases (46%) were TCRβ positive (αβ T), 5 (13%) were TCRγ and/or δ positive (γδ T), and 10 (26%) were TCR-silent type with clonal TCRγ gene rearrangement but no expression of TCRβ, γ, or δ. These results were clearly contrasted by a lower incidence of T-cell lineage in ENKTL (7 cases, 26%, P<0.001). Notably, the survival time of the 5 nodal lymphoma patients with γδ T-cell phenotype was within 3 months, which was inferior to those of αβ T and TCR-silent types (P=0.003), and 3 of those with available clinical information were all found to be associated with autoimmune diseases. These data suggest that nodal EBV CTL is distinct from ENKTL.

  2. Diffusion Experiments in Opalinus Clay: Laboratory, Large-Scale Diffusion Experiments and Microscale Analysis by RBS.

    Energy Technology Data Exchange (ETDEWEB)

    Garcia-Gutierrez, M.; Alonso de los Rios, U.; Missana, T.; Cormenzana, J.L.; Mingarro, M.; Morejon, J.; Gil, P.

    2008-08-06

    The Opalinus Clay (OPA) formation in the Zurcher Weiland (Switzerland) is a potential host rock for a repository for high-level radioactive waste. Samples collected in the Mont Terri Underground Rock Laboratory (URL), where the OPA formation is located at a depth between -200 and -300 m below the surface, were used to study the radionuclide diffusion in clay materials. Classical laboratory essays and a novel experimental set-up for large-scale diffusion experiments were performed together to a novel application of the nuclear ion beam technique Rutherford Backscattering Spectrometry (RBS), to understand the transport properties of the OPA and to enhance the methodologies used for in situ diffusion experiments. Through-Diffusion and In-Diffusion conventional laboratory diffusion experiments were carried out with HTO, 36{sup C}l-, I-, 22{sup N}a, 75{sup S}e, 85{sup S}r, 233{sup U}, 137{sup C}s, 60{sup C}o and 152{sup E}u. Large-scale diffusion experiments were performed with HTO, 36{sup C}l, and 85{sup S}r, and new experiments with 60{sup C}o, 137{sup C}s and 152{sup E}u are ongoing. Diffusion experiments with RBS technique were done with Sr, Re, U and Eu. (Author) 38 refs.

  3. Diffuse reflectance relations based on diffusion dipole theory for large absorption and reduced scattering.

    Science.gov (United States)

    Bremmer, Rolf H; van Gemert, Martin J C; Faber, Dirk J; van Leeuwen, Ton G; Aalders, Maurice C G

    2013-08-01

    Diffuse reflectance spectra are used to determine the optical properties of biological samples. In medicine and forensic science, the turbid objects under study often possess large absorption and/or scattering properties. However, data analysis is frequently based on the diffusion approximation to the radiative transfer equation, implying that it is limited to tissues where the reduced scattering coefficient dominates over the absorption coefficient. Nevertheless, up to absorption coefficients of 20  mm-1 at reduced scattering coefficients of 1 and 11.5  mm-1, we observed excellent agreement (r2=0.994) between reflectance measurements of phantoms and the diffuse reflectance equation proposed by Zonios et al. [Appl. Opt.38, 6628-6637 (1999)], derived as an approximation to one of the diffusion dipole equations of Farrell et al. [Med. Phys.19, 879-888 (1992)]. However, two parameters were fitted to all phantom experiments, including strongly absorbing samples, implying that the reflectance equation differs from diffusion theory. Yet, the exact diffusion dipole approximation at high reduced scattering and absorption also showed agreement with the phantom measurements. The mathematical structure of the diffuse reflectance relation used, derived by Zonios et al. [Appl. Opt.38, 6628-6637 (1999)], explains this observation. In conclusion, diffuse reflectance relations derived as an approximation to the diffusion dipole theory of Farrell et al. can analyze reflectance ratios accurately, even for much larger absorption than reduced scattering coefficients. This allows calibration of fiber-probe set-ups so that the object's diffuse reflectance can be related to its absorption even when large. These findings will greatly expand the application of diffuse reflection spectroscopy. In medicine, it may allow the use of blue/green wavelengths and measurements on whole blood, and in forensic science, it may allow inclusion of objects such as blood stains and cloth at crime

  4. Interleukin 10 gene promoter polymorphism and risk of diffuse large ...

    African Journals Online (AJOL)

    Purpose: Given the importance of understanding the genetic variations involved in the pathogenesis of non-Hodgkin's lymphoma (NHL), this work was designed to study the impact of IL-10 (1082 G/A; rs1800896 and 819 C/T; rs1800871) gene promoter polymorphism on susceptibility of Egyptians to diffuse large B cell ...

  5. Profiling of diffuse large B-cell lymphoma by immunohistochemistry

    DEFF Research Database (Denmark)

    Sjö, Lene Dissing; Poulsen, Christian Bjørn; Hansen, Mads

    2007-01-01

    Diffuse large B-cell lymphoma (DLBCL) is a frequent lymphoma subtype with a heterogeneous behavior and a variable response to conventional chemotherapy. This clinical diversity is believed to reflect differences in the molecular pathways leading to lymphomagenesis. In this study, we have analyzed...

  6. Large scale laboratory diffusion experiments in clay rocks

    International Nuclear Information System (INIS)

    Garcia-Gutierrez, M.; Missana, T.; Mingarro, M.; Martin, P.L.; Cormenzana, J.L.

    2005-01-01

    Full text of publication follows: Clay formations are potential host rocks for high-level radioactive waste repositories. In clay materials the radionuclide diffusion is the main transport mechanism. Thus, the understanding of the diffusion processes and the determination of diffusion parameters in conditions as similar as possible to the real ones, are critical for the performance assessment of deep geological repository. Diffusion coefficients are mainly measured in the laboratory using small samples, after a preparation to fit into the diffusion cell. In addition, a few field tests are usually performed for confirming laboratory results, and analyse scale effects. In field or 'in situ' tests the experimental set-up usually includes the injection of a tracer diluted in reconstituted formation water into a packed off section of a borehole. Both experimental systems may produce artefacts in the determination of diffusion coefficients. In laboratory the preparation of the sample can generate structural change mainly if the consolidated clay have a layered fabric, and in field test the introduction of water could modify the properties of the saturated clay in the first few centimeters, just where radionuclide diffusion is expected to take place. In this work, a large scale laboratory diffusion experiment is proposed, using a large cylindrical sample of consolidated clay that can overcome the above mentioned problems. The tracers used were mixed with clay obtained by drilling a central hole, re-compacted into the hole at approximately the same density as the consolidated block and finally sealed. Neither additional treatment of the sample nor external monitoring are needed. After the experimental time needed for diffusion to take place (estimated by scoping calculations) the block was sampled to obtain a 3D distribution of the tracer concentration and the results were modelled. An additional advantage of the proposed configuration is that it could be used in 'in situ

  7. Large Deviations for Two-Time-Scale Diffusions, with Delays

    International Nuclear Information System (INIS)

    Kushner, Harold J.

    2010-01-01

    We consider the problem of large deviations for a two-time-scale reflected diffusion process, possibly with delays in the dynamical terms. The Dupuis-Ellis weak convergence approach is used. It is perhaps the most intuitive and simplest for the problems of concern. The results have applications to the problem of approximating optimal controls for two-time-scale systems via use of the averaged equation.

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

    International Nuclear Information System (INIS)

    Carlos Bortoluzzi, Marcelo

    2010-01-01

    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)

  9. The ESO Diffuse Interstellar Band Large Exploration Survey (EDIBLES)

    Science.gov (United States)

    Cami, J.; Cox, N. L.; Farhang, A.; Smoker, J.; Elyajouri, M.; Lallement, R.; Bacalla, X.; Bhatt, N. H.; Bron, E.; Cordiner, M. A.; de Koter, A..; Ehrenfreund, P.; Evans, C.; Foing, B. H.; Javadi, A.; Joblin, C.; Kaper, L.; Khosroshahi, H. G.; Laverick, M.; Le Petit, F..; Linnartz, H.; Marshall, C. C.; Monreal-Ibero, A.; Mulas, G.; Roueff, E.; Royer, P.; Salama, F.; Sarre, P. J.; Smith, K. T.; Spaans, M.; van Loon, J. T..; Wade, G.

    2018-03-01

    The ESO Diffuse Interstellar Band Large Exploration Survey (EDIBLES) is a Large Programme that is collecting high-signal-to-noise (S/N) spectra with UVES of a large sample of O and B-type stars covering a large spectral range. The goal of the programme is to extract a unique sample of high-quality interstellar spectra from these data, representing different physical and chemical environments, and to characterise these environments in great detail. An important component of interstellar spectra is the diffuse interstellar bands (DIBs), a set of hundreds of unidentified interstellar absorption lines. With the detailed line-of-sight information and the high-quality spectra, EDIBLES will derive strong constraints on the potential DIB carrier molecules. EDIBLES will thus guide the laboratory experiments necessary to identify these interstellar “mystery molecules”, and turn DIBs into powerful diagnostics of their environments in our Milky Way Galaxy and beyond. We present some preliminary results showing the unique capabilities of the EDIBLES programme.

  10. Knowledge diffusion within a large conservation organization and beyond

    Science.gov (United States)

    Montambault, Jensen; Burford, Kyle P.; Gopalakrishna, Trisha; Masuda, Yuta J.; Reddy, Sheila M. W.; Torphy, Kaitlin; Salcedo, Andrea I.

    2018-01-01

    The spread and uptake of new ideas (diffusion of innovations) is critical for organizations to adapt over time, but there is little evidence of how this happens within organizations and to their broader community. To address this, we analyzed how individuals accessed information about a recent science innovation at a large, international, biodiversity conservation non-profit–The Nature Conservancy–and then traced the flow of how this information was shared within the organization and externally, drawing on an exceptionally data-rich environment. We used surveys and tracking of individual internet activity to understand mechanisms for early-stage diffusion (knowledge seeking and sharing) following the integration of social science and evidence principles into the institutional planning framework: Conservation by Design (CbD 2.0). Communications sent to all employees effectively catalyzed 56.4% to exhibit knowledge seeking behavior, measured by individual downloads from and visits to a restricted-access site. Individuals who self-reported through a survey that they shared information about CbD 2.0 internally were more likely to have both received and sought out information about the framework. Such individuals tended to hold positions within a higher job grade, were more likely to train others on CbD as part of their job, and to enroll in other online professional development offerings. Communication strategies targeting external audiences did not appear to influence information seeking behavior. Staff who engaged in internal knowledge sharing and adopting “evidence” practices from CbD 2.0 were more likely to have shared the document externally. We found a negative correlation with external sharing behavior and in-person trainings. Our findings suggest repeated, direct email communications aimed at wide audiences can effectively promote diffusion of new ideas. We also found a wide range of employee characteristics and circumstances to be associated with

  11. Knowledge diffusion within a large conservation organization and beyond.

    Science.gov (United States)

    Fisher, Jonathan R B; Montambault, Jensen; Burford, Kyle P; Gopalakrishna, Trisha; Masuda, Yuta J; Reddy, Sheila M W; Torphy, Kaitlin; Salcedo, Andrea I

    2018-01-01

    The spread and uptake of new ideas (diffusion of innovations) is critical for organizations to adapt over time, but there is little evidence of how this happens within organizations and to their broader community. To address this, we analyzed how individuals accessed information about a recent science innovation at a large, international, biodiversity conservation non-profit-The Nature Conservancy-and then traced the flow of how this information was shared within the organization and externally, drawing on an exceptionally data-rich environment. We used surveys and tracking of individual internet activity to understand mechanisms for early-stage diffusion (knowledge seeking and sharing) following the integration of social science and evidence principles into the institutional planning framework: Conservation by Design (CbD 2.0). Communications sent to all employees effectively catalyzed 56.4% to exhibit knowledge seeking behavior, measured by individual downloads from and visits to a restricted-access site. Individuals who self-reported through a survey that they shared information about CbD 2.0 internally were more likely to have both received and sought out information about the framework. Such individuals tended to hold positions within a higher job grade, were more likely to train others on CbD as part of their job, and to enroll in other online professional development offerings. Communication strategies targeting external audiences did not appear to influence information seeking behavior. Staff who engaged in internal knowledge sharing and adopting "evidence" practices from CbD 2.0 were more likely to have shared the document externally. We found a negative correlation with external sharing behavior and in-person trainings. Our findings suggest repeated, direct email communications aimed at wide audiences can effectively promote diffusion of new ideas. We also found a wide range of employee characteristics and circumstances to be associated with knowledge

  12. Rituximab and chemotherapy in diffuse large B-cell lymphoma.

    Science.gov (United States)

    Sonet, Anne; Bosly, André

    2009-06-01

    Rituximab is an anti-CD20 chimeric monoclonal antibody with activity in nearly all subtypes of B-cell lymphomas. Association of rituximab with chemotherapy (mostly the cyclophosphamide, doxorubicin, vincristine and prednisolone [CHOP] regimen) in diffuse large B-cell lymphoma (DLBCL) represents an extraordinary revolution in the prognosis of DLBCL, and is the new standard of therapy in elderly and young, low-risk patients. Despite the lack of randomized, clinical trials in younger patients with high risk, rituximab is also a standard of care in these patients in clinical practice, at least in North America. The practice is based on observational trials (e.g., the British Columbia Registry) and the missing logic in classifying patients as 'younger' or 'older': 60 years old or 65 years old. In Europe, trials are ongoing to establish the best treatment for young, high-risk patients. Association of rituximab and chemotherapy deeply modifies prognostic factors defined before the rituximab era.

  13. 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.

  14. Cerebral toxoplasmosis in a diffuse large B cell lymphoma patient

    International Nuclear Information System (INIS)

    Savsek, Lina; Opaskar, Tanja Ros

    2016-01-01

    Toxoplasmosis is an opportunistic protozoal infection that has, until now, probably been an underestimated cause of encephalitis in patients with hematological malignancies, independent of stem cell or bone marrow transplant. T and B cell depleting regimens are probably an important risk factor for reactivation of a latent toxoplasma infection in these patients. We describe a 62-year-old HIV-negative right-handed Caucasian female with systemic diffuse large B cell lymphoma who presented with sudden onset of high fever, headache, altered mental status, ataxia and findings of pancytopenia, a few days after receiving her final, 8 th cycle of rituximab, cyclophosphamide, vincristine, doxorubicin, prednisolone (R-CHOP) chemotherapy regimen. A progression of lymphoma to the central nervous system was suspected. MRI of the head revealed multiple on T2 and fluid attenuated inversion recovery (FLAIR) hyperintense parenchymal lesions with mild surrounding edema, located in both cerebral and cerebellar hemispheres that demonstrated moderate gadolinium enhancement. The polymerase chain reaction on cerebrospinal fluid (CSF PCR) was positive for Toxoplasma gondii. The patient was diagnosed with toxoplasmic encephalitis and successfully treated with sulfadiazine, pyrimethamine and folic acid. Due to the need for maintenance therapy with rituximab for lymphoma remission, the patient now continues with secondary prophylaxis of toxoplasmosis. With this case report, we wish to emphasize the need to consider cerebral toxoplasmosis in patients with hematological malignancies on immunosuppressive therapy when presenting with new neurologic deficits. In such patients, there are numerous differential diagnoses for cerebral toxoplasmosis, and the CNS lymphoma is the most difficult among all to distinguish it from. If left untreated, cerebral toxoplasmosis has a high mortality rate; therefore early recognition and treatment are of essential importance

  15. Genetics and Pathogenesis of Diffuse Large B-Cell Lymphoma.

    Science.gov (United States)

    Schmitz, Roland; Wright, George W; Huang, Da Wei; Johnson, Calvin A; Phelan, James D; Wang, James Q; Roulland, Sandrine; Kasbekar, Monica; Young, Ryan M; Shaffer, Arthur L; Hodson, Daniel J; Xiao, Wenming; Yu, Xin; Yang, Yandan; Zhao, Hong; Xu, Weihong; Liu, Xuelu; Zhou, Bin; Du, Wei; Chan, Wing C; Jaffe, Elaine S; Gascoyne, Randy D; Connors, Joseph M; Campo, Elias; Lopez-Guillermo, Armando; Rosenwald, Andreas; Ott, German; Delabie, Jan; Rimsza, Lisa M; Tay Kuang Wei, Kevin; Zelenetz, Andrew D; Leonard, John P; Bartlett, Nancy L; Tran, Bao; Shetty, Jyoti; Zhao, Yongmei; Soppet, Dan R; Pittaluga, Stefania; Wilson, Wyndham H; Staudt, Louis M

    2018-04-12

    Diffuse large B-cell lymphomas (DLBCLs) are phenotypically and genetically heterogeneous. Gene-expression profiling has identified subgroups of DLBCL (activated B-cell-like [ABC], germinal-center B-cell-like [GCB], and unclassified) according to cell of origin that are associated with a differential response to chemotherapy and targeted agents. We sought to extend these findings by identifying genetic subtypes of DLBCL based on shared genomic abnormalities and to uncover therapeutic vulnerabilities based on tumor genetics. We studied 574 DLBCL biopsy samples using exome and transcriptome sequencing, array-based DNA copy-number analysis, and targeted amplicon resequencing of 372 genes to identify genes with recurrent aberrations. We developed and implemented an algorithm to discover genetic subtypes based on the co-occurrence of genetic alterations. We identified four prominent genetic subtypes in DLBCL, termed MCD (based on the co-occurrence of MYD88 L265P and CD79B mutations), BN2 (based on BCL6 fusions and NOTCH2 mutations), N1 (based on NOTCH1 mutations), and EZB (based on EZH2 mutations and BCL2 translocations). Genetic aberrations in multiple genes distinguished each genetic subtype from other DLBCLs. These subtypes differed phenotypically, as judged by differences in gene-expression signatures and responses to immunochemotherapy, with favorable survival in the BN2 and EZB subtypes and inferior outcomes in the MCD and N1 subtypes. Analysis of genetic pathways suggested that MCD and BN2 DLBCLs rely on "chronic active" B-cell receptor signaling that is amenable to therapeutic inhibition. We uncovered genetic subtypes of DLBCL with distinct genotypic, epigenetic, and clinical characteristics, providing a potential nosology for precision-medicine strategies in DLBCL. (Funded by the Intramural Research Program of the National Institutes of Health and others.).

  16. Logical analysis of diffuse large B-cell lymphomas.

    Science.gov (United States)

    Alexe, G; Alexe, S; Axelrod, D E; Hammer, P L; Weissmann, D

    2005-07-01

    The goal of this study is to re-examine the oligonucleotide microarray dataset of Shipp et al., which contains the intensity levels of 6817 genes of 58 patients with diffuse large B-cell lymphoma (DLBCL) and 19 with follicular lymphoma (FL), by means of the combinatorics, optimisation, and logic-based methodology of logical analysis of data (LAD). The motivations for this new analysis included the previously demonstrated capabilities of LAD and its expected potential (1) to identify different informative genes than those discovered by conventional statistical methods, (2) to identify combinations of gene expression levels capable of characterizing different types of lymphoma, and (3) to assemble collections of such combinations that if considered jointly are capable of accurately distinguishing different types of lymphoma. The central concept of LAD is a pattern or combinatorial biomarker, a concept that resembles a rule as used in decision tree methods. LAD is able to exhaustively generate the collection of all those patterns which satisfy certain quality constraints, through a systematic combinatorial process guided by clear optimization criteria. Then, based on a set covering approach, LAD aggregates the collection of patterns into classification models. In addition, LAD is able to use the information provided by large collections of patterns in order to extract subsets of variables, which collectively are able to distinguish between different types of disease. For the differential diagnosis of DLBCL versus FL, a model based on eight significant genes is constructed and shown to have a sensitivity of 94.7% and a specificity of 100% on the test set. For the prognosis of good versus poor outcome among the DLBCL patients, a model is constructed on another set consisting also of eight significant genes, and shown to have a sensitivity of 87.5% and a specificity of 90% on the test set. The genes selected by LAD also work well as a basis for other kinds of statistical

  17. An homeopathic cure to pure Xenon large diffusion

    CERN Document Server

    Azevedo, C.D.R.; Freitas, E.D.C.; Gonzalez-Diaz, D.; Monrabal, F.; Monteiro, C.M.B.; dos Santos, J. M. F.; Veloso, J.F.C.A.; Gomez-Cadenas, J. J

    2016-02-03

    The NEXT neutrinoless double beta decay experiment will use a high- pressure gas electroluminescence-based TPC to search for the decay of Xe-136. One of the main advantages of this technology is the possibility to reconstruct the topology of events with energies close to Qbb. The rejection potential associated to the topology reconstruction is limited by our capacity to prop- erly reconstruct the original path of the electrons in the gas. This reconstruction is limited by different factors that include the geometry of the detector, the density of the sensors in the tracking plane and the separation among them, etc. Ultimately, the resolution is limited by the physics of electron diffusion in the gas. In this paper we present a series of molecular additives that can be used in Xenon gas at very low partial pressure to reduce both longitudinal and transverse diffusion. We will show the results of different Monte-Carlo simulations of electron transport in the gas mixtures from wich we have extracted the value of...

  18. Primary Diffuse Large Cell Lymphoma of the Bladder: Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Mansour Ansari

    2017-01-01

    Full Text Available Most bladder tumors are epithelial in origin. Nonepithelial cancers are rarely located in the bladder. Sarcomas are the most common malignancies among nonepithelial cancers. Primary bladder lymphoma is rare and mostly low grade. Here, we have reported a case of diffuse large cell lymphoma of the bladder. The patient, a 64-year-old man, had urinary frequency for 18 months. Abdominal sonography indicated a thick bladder wall and transurethral biopsy showed diffuse large cell lymphoma. Immunohistochemistry (IHC results showed that the tumor was positive for CD20, CD45, and Pax-5 and negative for BCL-2, cytokeratin, and S100. He had a normal bone marrow biopsy, abdominal, pelvic and chest CT scans. He had no B symptoms. The patient received 6 cycles of R-CHOP followed by radiotherapy (36 Gy to the pelvis. Six months after treatment, the patient is well and has returned to work. We have searched PubMed for primary diffuse large cell lymphoma. Primary diffuse large cell lymphoma of the bladder is best treated according to treatment for diffuse large cell lymphoma of other sites, which includes chemotherapy and radiotherapy. As seen in our review, primary diffuse large cell lymphoma of the bladder has a similar clinical course to diffuse large cell lymphoma of other sites.

  19. Large-time behavior of solutions to a reaction-diffusion system with distributed microstructure

    NARCIS (Netherlands)

    Muntean, A.

    2009-01-01

    Abstract We study the large-time behavior of a class of reaction-diffusion systems with constant distributed microstructure arising when modeling diffusion and reaction in structured porous media. The main result of this Note is the following: As t ¿ 8 the macroscopic concentration vanishes, while

  20. Flow structures in large-angle conical diffusers measured by PIV

    DEFF Research Database (Denmark)

    Meyer, Knud Erik; Nielsen, L.; Nielsen, N.F.

    2004-01-01

    Flow in two different conical diffusers with large opening angles (30° and 18°) have been measured with stereoscopic Particle Image Velocimetry (PIV). The measurements were done in a cross section just after the exit of the diffuser. The Reynolds number was 100000 based on upstream diameter...

  1. Primary Diffuse Large Cell Lymphoma of the Bladder: Case Report and Literature Review

    OpenAIRE

    Mansour Ansari; Hamid Nasrollahi; Majdaddin Rajaei; Maral Mokhtari; Seyed Hasan Hamedi; Mohammad Mohammadianpanah; Shapour Omidvari; Ahmad Mosalaei; Niloofar Ahmadloo

    2017-01-01

    Most bladder tumors are epithelial in origin. Nonepithelial cancers are rarely located in the bladder. Sarcomas are the most common malignancies among nonepithelial cancers. Primary bladder lymphoma is rare and mostly low grade. Here, we have reported a case of diffuse large cell lymphoma of the bladder. The patient, a 64-year-old man, had urinary frequency for 18 months. Abdominal sonography indicated a thick bladder wall and transurethral biopsy showed diffuse large cell lymp...

  2. Diffusion

    International Nuclear Information System (INIS)

    Kubaschewski, O.

    1983-01-01

    The diffusion rate values of titanium, its compounds and alloys are summarized and tabulated. The individual chemical diffusion coefficients and self-diffusion coefficients of certain isotopes are given. Experimental methods are listed which were used for the determination of diffusion coefficients. Some values have been taken over from other studies. Also given are graphs showing the temperature dependences of diffusion and changes in the diffusion coefficient with concentration changes

  3. Large Time Asymptotics for a Continuous Coagulation-Fragmentation Model with Degenerate Size-Dependent Diffusion

    KAUST Repository

    Desvillettes, Laurent

    2010-01-01

    We study a continuous coagulation-fragmentation model with constant kernels for reacting polymers (see [M. Aizenman and T. Bak, Comm. Math. Phys., 65 (1979), pp. 203-230]). The polymers are set to diffuse within a smooth bounded one-dimensional domain with no-flux boundary conditions. In particular, we consider size-dependent diffusion coefficients, which may degenerate for small and large cluster-sizes. We prove that the entropy-entropy dissipation method applies directly in this inhomogeneous setting. We first show the necessary basic a priori estimates in dimension one, and second we show faster-than-polynomial convergence toward global equilibria for diffusion coefficients which vanish not faster than linearly for large sizes. This extends the previous results of [J.A. Carrillo, L. Desvillettes, and K. Fellner, Comm. Math. Phys., 278 (2008), pp. 433-451], which assumes that the diffusion coefficients are bounded below. © 2009 Society for Industrial and Applied Mathematics.

  4. Relationship between pretreatment FDG-PET and diffusion-weighted MRI biomarkers in diffuse large B-cell lymphoma

    Science.gov (United States)

    de Jong, Antoinette; Kwee, Thomas C; de Klerk, John MH; Adam, Judit A; de Keizer, Bart; Fijnheer, Rob; Kersten, Marie José; Ludwig, Inge; Jauw, Yvonne WS; Zijlstra, Josée M; den Bos, Indra C Pieters - Van; Stoker, Jaap; Hoekstra, Otto S; Nievelstein, Rutger AJ

    2014-01-01

    The purpose of this study was to determine the correlation between the 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) standardized uptake value (SUV) and the diffusion-weighted magnetic resonance imaging (MRI) apparent diffusion coefficient (ADC) in newly diagnosed diffuse large B-cell lymphoma (DLBCL). Pretreatment FDG-PET and diffusion-weighted MRI of 21 patients with histologically proven DLBCL were prospectively analyzed. In each patient, maximum, mean and peak standardized uptake value (SUV) was measured in the lesion with visually highest FDG uptake and in the largest lesion. Mean ADC (ADCmean, calculated with b-values of 0 and 1000 s/mm2) was measured in the same lesions. Correlations between FDG-PET metrics (SUVmax, SUVmean, SUVpeak) and ADCmean were assessed using Pearson’s correlation coefficients. In the lesions with visually highest FDG uptake, no significant correlations were found between the SUVmax, SUVmean, SUVpeak and the ADCmean (P=0.498, P=0.609 and P=0.595, respectively). In the largest lesions, there were no significant correlations either between the SUVmax, SUVmean, SUVpeak and the ADCmean (P=0.992, P=0.843 and P=0.894, respectively). The results of this study indicate that the glycolytic rate as measured by FDG-PET and changes in water compartmentalization and water diffusion as measured by the ADC are independent biological phenomena in newly diagnosed DLBCL. Further studies are warranted to assess the complementary roles of these different imaging biomarkers in the evaluation and follow-up of DLBCL. PMID:24795837

  5. Modeling of electromagnetic and thermal diffusion in a large pure aluminum stabilized superconductor under quench

    CERN Document Server

    Gavrilin, A V

    2001-01-01

    Low temperature composite superconductors stabilized with extra large cross-section pure aluminum are currently in use for the Large Helical Device in Japan, modern big detectors such as ATLAS at CERN, and other large magnets. In these types of magnet systems, the rated average current density is not high and the peak field in a region of interest is about 2-4 T. Aluminum stabilized superconductors result in high stability margins and relatively long quench times. Appropriate quench analyses, both for longitudinal and transverse propagation, have to take into account a rather slow diffusion of current from the superconductor into the thick aluminum stabilizer. An exact approach to modeling of the current diffusion would be based on directly solving the Maxwell's equations in parallel with thermal diffusion and conduction relations. However, from a practical point of view, such an approach should be extremely time consuming due to obvious restrictions of computation capacity. At the same time, there exist cert...

  6. Avelumab, Utomilumab, Rituximab, Ibrutinib, and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma or Mantle Cell Lymphoma

    Science.gov (United States)

    2018-06-13

    CCND1 Positive; CD20 Positive; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mantle Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mantle Cell Lymphoma; Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma

  7. Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy in Relapsed or Refractory Diffuse Large B-Cell Lymphoma

    DEFF Research Database (Denmark)

    van Imhoff, Gustaaf W; McMillan, Andrew; Matasar, Matthew J

    2017-01-01

    Purpose We compared the efficacy of ofatumumab (O) versus rituximab (R) in combination with cisplatin, cytarabine, and dexamethasone (DHAP) salvage treatment, followed by autologous stem-cell transplantation (ASCT) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Pat...

  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

    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...

  9. Prognosis of localized diffuse large B-cell lymphoma in younger patients

    DEFF Research Database (Denmark)

    Møller, Michael B; Christensen, Bjarne E; Pedersen, Niels T

    2003-01-01

    BACKGROUND: The International Prognostic Index (IPI) is widely used as a predictive model in diffuse large B-cell lymphoma (DLBCL) patients of all ages and stages. To determine the optimal IPI-based prognostic system at the time of diagnosis in younger patients with limited-stage DLBCL, the authors...

  10. Role of Radiation Therapy in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma

    DEFF Research Database (Denmark)

    Ng, Andrea K; Yahalom, Joachim; Goda, Jayant S

    2018-01-01

    Approximately 30% to 40% of patients with diffuse large B-cell lymphoma (DLBCL) will have either primary refractory disease or relapse after chemotherapy. In transplant-eligible patients, those with disease sensitive to salvage chemotherapy will significantly benefit from high-dose therapy with a...

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

    DEFF Research Database (Denmark)

    Møller, Michael Boe; Kania, P W; 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...

  12. Genetic and Functional Drivers of Diffuse Large B Cell Lymphoma

    DEFF Research Database (Denmark)

    Reddy, Anupama; Zhang, Jenny; Davis, Nicholas S

    2017-01-01

    Diffuse large B cell lymphoma (DLBCL) is the most common form of blood cancer and is characterized by a striking degree of genetic and clinical heterogeneity. This heterogeneity poses a major barrier to understanding the genetic basis of the disease and its response to therapy. Here, we performed...

  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. Simplicity at the cost of predictive accuracy in diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Biccler, Jorne Lionel; Eloranta, Sandra; Brown, Peter de Nully

    2018-01-01

    The international prognostic index (IPI) and similar models form the cornerstone of clinical assessment in newly diagnosed diffuse large B-cell lymphoma (DLBCL). While being simple and convenient to use, their inadequate use of the available clinical data is a major weakness. In this study, we co...

  15. Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma

    NARCIS (Netherlands)

    Cerhan, James R.; Berndt, Sonja I.; Vijai, Joseph; Ghesquières, Hervé; McKay, James; Wang, Sophia S.; Wang, Zhaoming; Yeager, Meredith; Conde, Lucia; De Bakker, Paul I W; Nieters, Alexandra; Cox, David; Burdett, Laurie; Monnereau, Alain; Flowers, Christopher R.; De Roos, Anneclaire J.; Brooks-Wilson, Angela R.; Lan, Qing; Severi, Gianluca; Melbye, Mads; Gu, Jian; Jackson, Rebecca D.; Kane, Eleanor; Teras, Lauren R.; Purdue, Mark P.; Vajdic, Claire M.; Spinelli, John J.; Giles, Graham G.; Albanes, Demetrius; Kelly, Rachel S.; Zucca, Mariagrazia; Bertrand, Kimberly A.; Zeleniuch-Jacquotte, Anne; Lawrence, Charles; Hutchinson, Amy; Zhi, Degui; Habermann, Thomas M.; Link, Brian K.; Novak, Anne J.; Dogan, Ahmet; Asmann, Yan W.; Liebow, Mark; Thompson, Carrie A.; Ansell, Stephen M.; Witzig, Thomas E.; Weiner, George J.; Veron, Amelie S.; Zelenika, Diana; Tilly, Hervé; Haioun, Corinne; Molina, Thierry Jo; Hjalgrim, Henrik; Glimelius, Bengt; Adami, Hans Olov; Bracci, Paige M.; Riby, Jacques; Smith, Martyn T.; Holly, Elizabeth A.; Cozen, Wendy; Hartge, Patricia; Morton, Lindsay M.; Severson, Richard K.; Tinker, Lesley F.; North, Kari E.; Becker, Nikolaus; Benavente, Yolanda; Boffetta, Paolo; Brennan, Paul; Foretova, Lenka; Maynadie, Marc; Staines, Anthony; Lightfoot, Tracy; Crouch, Simon; Smith, Alex; Roman, Eve; Diver, W. Ryan; Offit, Kenneth; Zelenetz, Andrew; Klein, Robert J.; Villano, Danylo J.; Zheng, Tongzhang; Zhang, Yawei; Holford, Theodore R.; Kricker, Anne; Turner, Jenny; Southey, Melissa C.; Clavel, Jacqueline; Virtamo, Jarmo; Weinstein, Stephanie; Riboli, Elio; Vineis, Paolo; Kaaks, Rudolph; Trichopoulos, Dimitrios; Vermeulen, Roel C H; Boeing, Heiner; Tjonneland, Anne; Angelucci, Emanuele; Di Lollo, Simonetta; Rais, Marco; Birmann, Brenda M.; Laden, Francine; Giovannucci, Edward; Kraft, Peter; Huang, Jinyan; Ma, Baoshan; Ye, Yuanqing; Chiu, Brian C H; Sampson, Joshua; Liang, Liming; Park, Ju Hyun; Chung, Charles C.; Weisenburger, Dennis D.; Chatterjee, Nilanjan; Fraumeni, Joseph F.; Slager, Susan L.; Wu, Xifeng; De Sanjose, Silvia; Smedby, Karin E.; Salles, Gilles; Skibola, Christine F.; Rothman, Nathaniel; Chanock, Stephen J.

    2014-01-01

    Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma subtype and is clinically aggressive. To identify genetic susceptibility loci for DLBCL, we conducted a meta-analysis of 3 new genome-wide association studies (GWAS) and 1 previous scan, totaling 3,857 cases and 7,666 controls of

  16. Lupus-related single nucleotide polymorphisms and risk of diffuse large B-cell lymphoma

    NARCIS (Netherlands)

    Bernatsky, Sasha; Velásquez García, Héctor A; Spinelli, John; Gaffney, Patrick; Smedby, Karin E; Ramsey-Goldman, Rosalind; Wang, Sophia S.; Adami, Hans-Olov; Albanes, Demetrius; Angelucci, Emanuele; Ansell, Stephen M.; Asmann, Yan W.; Becker, Nikolaus; Benavente, Yolanda; Berndt, Sonja I.; Bertrand, Kimberly A.; Birmann, Brenda M.; Boeing, Heiner; Boffetta, Paolo; Bracci, Paige M.; Brennan, Paul; Brooks-Wilson, Angela R.; Cerhan, James R.; Chanock, Stephen J.; Clavel, Jacqueline; Conde, Lucia; Cotenbader, Karen H; Cox, David G; Cozen, Wendy; Crouch, Simon; De Roos, Anneclaire J.; De Sanjose, Silvia; Di Lollo, Simonetta; Diver, W. Ryan; Dogan, Ahmet; Foretova, Lenka; Ghesquières, Hervé; Giles, Graham G.; Glimelius, Bengt; Habermann, Thomas M.; Haioun, Corinne; Hartge, Patricia; Hjalgrim, Henrik; Holford, Theodore R.; Holly, Elizabeth A.; Jackson, Rebecca D.; Kaaks, Rudolph; Kane, Eleanor; Kelly, Rachel S.; Klein, Robert J.; Kraft, Peter; Kricker, Anne; Lan, Qing; Lawrence, Charles; Liebow, Mark; Lightfoot, Tracy; Link, Brian K.; Maynadie, Marc; McKay, James; Melbye, Mads; Molina, Thierry Jo; Monnereau, Alain; Morton, Lindsay M.; Nieters, Alexandra; North, Kari E.; Novak, Anne J.; Offit, Kenneth; Purdue, Mark P.; Rais, Marco; Riby, Jacques; Roman, Eve; Rothman, Nathaniel; Salles, Gilles; Severi, Gianluca; Severson, Richard K.; Skibola, Christine F.; Slager, Susan L.; Smith, Alex; Smith, Martyn T.; Southey, Melissa C.; Staines, Anthony; Teras, Lauren R.; Thompson, Carrie A.; Tilly, Hervé; Tinker, Lesley F.; Tjonneland, Anne; Turner, Jenny; Vajdic, Claire M.; Vermeulen, Roel C H; Vijai, Joseph; Vineis, Paolo; Virtamo, Jarmo; Wang, Zhaoming; Weinstein, Stephanie; Witzig, Thomas E.; Zelenetz, Andrew; Zeleniuch-Jacquotte, Anne; Zhang, Yawei; Zheng, Tongzhang; Zucca, Mariagrazia; Clarke, Ann E

    2017-01-01

    Objective: Determinants of the increased risk of diffuse large B-cell lymphoma (DLBCL) in SLE are unclear. Using data from a recent lymphoma genome-wide association study (GWAS), we assessed whether certain lupus-related single nucleotide polymorphisms (SNPs) were also associated with DLBCL.

  17. Large-eddy simulation with accurate implicit subgrid-scale diffusion

    NARCIS (Netherlands)

    B. Koren (Barry); C. Beets

    1996-01-01

    textabstractA method for large-eddy simulation is presented that does not use an explicit subgrid-scale diffusion term. Subgrid-scale effects are modelled implicitly through an appropriate monotone (in the sense of Spekreijse 1987) discretization method for the advective terms. Special attention is

  18. Production of a large area diffuse arc plasma with multiple cathode

    International Nuclear Information System (INIS)

    Wang Cheng; Cui Hai-Chao; Li Wan-Wan; Liao Meng-Ran; Xia Wei-Dong; Xia Wei-Luo

    2017-01-01

    An arc channel at atmospheric pressure tends to shrink generally. In this paper, a non-transferred DC arc plasma device with multiple cathode is introduced to produce a large area arc plasma at atmospheric pressure. This device is comprised of a 42-mm diameter tubular chamber, multiple cathode which is radially inserted into the chamber, and a tungsten anode with a nozzle in its center. In argon/helium atmosphere, a large area and circumferential homogenous diffuse arc plasma, which fills the entire cross section surrounded by the cathode tips, is observed. Results show that the uniformity and stability of diffuse arc plasma are strongly related to the plasma forming gas. Based on these experimental results, an explanation to the arc diffusion is suggested. Moreover, the electron excitation temperature and electron density measured in diffuse helium plasma are much lower than those of constricted arc column, which indicates the diffuse helium plasma probably deviates from the local thermodynamic equilibrium state. Unlike the common non-transferred arc plasma devices, this device can provide a condition for axial-fed feedstock particles. The plasma device is attempted to spheroidize alumina powders by using the central axis to send the powder. Results show that the powder produced is usually a typical hollow sphere. (paper)

  19. THEMIS Observations of the Magnetopause Electron Diffusion Region: Large Amplitude Waves and Heated Electrons

    Science.gov (United States)

    Tang, Xiangwei; Cattell, Cynthia; Dombeck, John; Dai, Lei; Wilson, Lynn B. III; Breneman, Aaron; Hupack, Adam

    2013-01-01

    We present the first observations of large amplitude waves in a well-defined electron diffusion region based on the criteria described by Scudder et al at the subsolar magnetopause using data from one Time History of Events and Macroscale Interactions during Substorms (THEMIS) satellite. These waves identified as whistler mode waves, electrostatic solitary waves, lower hybrid waves, and electrostatic electron cyclotron waves, are observed in the same 12 s waveform capture and in association with signatures of active magnetic reconnection. The large amplitude waves in the electron diffusion region are coincident with abrupt increases in electron parallel temperature suggesting strong wave heating. The whistler mode waves, which are at the electron scale and which enable us to probe electron dynamics in the diffusion region were analyzed in detail. The energetic electrons (approx. 30 keV) within the electron diffusion region have anisotropic distributions with T(sub e(right angle))/T(sub e(parallel)) > 1 that may provide the free energy for the whistler mode waves. The energetic anisotropic electrons may be produced during the reconnection process. The whistler mode waves propagate away from the center of the "X-line" along magnetic field lines, suggesting that the electron diffusion region is a possible source region of the whistler mode waves.

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

    International Nuclear Information System (INIS)

    Inaba, Koji; Morota, Madoka; Mayahara, Hiroshi; Ito, Yoshinori; Sumi, Minako; Uno, Takashi; Itami, Jun; Kushima, Ryoji; Murakami, Naoya; Kuroda, Yuuki; Harada, Ken; Kitaguchi, Mayuka; Yoshio, Kotaro; Sekii, Shuhei; Takahashi, Kana

    2013-01-01

    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

  1. A Characterization of the Diffuse Galactic Emissions at Large Angular Scales Using the Tenerife Data

    Directory of Open Access Journals (Sweden)

    J. F. Macías-Pérez

    2013-01-01

    diffuse emission in the range from 20 to 60 GHz. To discriminate between different models of AME, low frequency microwave data from 10 to 20 GHz are needed. We present here a reanalysis of published and unpublished Tenerife data from 10 to 33 GHz at large angular scales (from 5 to 15 degrees. We cross-correlate the Tenerife data to templates of the main galactic diffuse emissions: synchrotron, free-free, and thermal dust. We find evidence of dust-correlated emission in the Tenerife data that could be explained as spinning dust grain emission.

  2. Jump rates for surface diffusion of large molecules from first principles

    Energy Technology Data Exchange (ETDEWEB)

    Shea, Patrick, E-mail: patrick.shea@dal.ca; Kreuzer, Hans Jürgen [Department of Physics and Atmospheric Science, Dalhousie University, Halifax, Nova Scotia B3H 3J5 (Canada)

    2015-04-21

    We apply a recently developed stochastic model for the surface diffusion of large molecules to calculate jump rates for 9,10-dithioanthracene on a Cu(111) surface. The necessary input parameters for the stochastic model are calculated from first principles using density functional theory (DFT). We find that the inclusion of van der Waals corrections to the DFT energies is critical to obtain good agreement with experimental results for the adsorption geometry and energy barrier for diffusion. The predictions for jump rates in our model are in excellent agreement with measured values and show a marked improvement over transition state theory (TST). We find that the jump rate prefactor is reduced by an order of magnitude from the TST estimate due to frictional damping resulting from energy exchange with surface phonons, as well as a rotational mode of the diffusing molecule.

  3. MicroRNA expression in nodal and extranodal Diffuse Large B-cell Lymphoma

    DEFF Research Database (Denmark)

    Mandrup, Charlotte; Petersen, Anders; Højfeldt, Anne Dirks

    MicroRNA expression in nodal and extranodal Diffuse Large B-cell Lymphoma   C. Mandrup1, A. Petersen1, A. D. Hoejfeldt1, H. F. Thomsen1, J. Madsen1, J. Dahlgaard1, P. Johansen2, A. Bukh1, K. Dybkaer1 and H. E Johnsen1. 1Department of Hematology, 2Pathological Institute, Aalborg Hospital, Aarhus...... University Hospital, Aalborg, Denmark Introduction: The aim of this project was to analyse microRNA (miRNA) expression in nodal and extranodal diffuse large B-cell lymphoma (DLBCL). Manifestation at diagnosis may be nodal and/or extranodal. At present, there are no known determinants for none...... of the manifestations, and no way to predict the potential progression from nodal to extranodal disease. miRNA are small regulatory RNA molecules with core function to repress/cleave sequence complementary mRNA targets. Abnormalities in miRNA genetics and expression are known to affect initiation and development...

  4. Large-eddy simulation of a turbulent piloted methane/air diffusion flame (Sandia flame D)

    International Nuclear Information System (INIS)

    Pitsch, H.; Steiner, H.

    2000-01-01

    The Lagrangian Flamelet Model is formulated as a combustion model for large-eddy simulations of turbulent jet diffusion flames. The model is applied in a large-eddy simulation of a piloted partially premixed methane/air diffusion flame (Sandia flame D). The results of the simulation are compared to experimental data of the mean and RMS of the axial velocity and the mixture fraction and the unconditional and conditional averages of temperature and various species mass fractions, including CO and NO. All quantities are in good agreement with the experiments. The results indicate in accordance with experimental findings that regions of high strain appear in layer like structures, which are directed inwards and tend to align with the reaction zone, where the turbulence is fully developed. The analysis of the conditional temperature and mass fractions reveals a strong influence of the partial premixing of the fuel. (c) 2000 American Institute of Physics

  5. Large diffusion anisotropy and orientation sorting of phosphorene nanoflakes under a temperature gradient.

    Science.gov (United States)

    Cheng, Yuan; Zhang, Gang; Zhang, Yingyan; Chang, Tienchong; Pei, Qing-Xiang; Cai, Yongqing; Zhang, Yong-Wei

    2018-01-25

    We perform molecular dynamics simulations to investigate the motion of phosphorene nanoflakes on a large graphene substrate under a thermal gradient. It is found that the atomic interaction between the graphene substrate and the phosphorene nanoflake generates distinct rates of motion for phosphorene nanoflakes with different orientations. Remarkably, for square phosphorene nanoflakes, the motion of zigzag-oriented nanoflakes is 2-fold faster than those of armchair-oriented and randomly-oriented nanoflakes. This large diffusion anisotropy suggests that sorting of phosphorene nanoflakes into specific orientations can be realized by a temperature gradient. The findings here provide interesting insights into strong molecular diffusion anisotropy and offer a novel route for manipulating two-dimensional materials.

  6. Capgras syndrome associated with limbic encephalitis in a patient with diffuse large B-cell lymphoma

    OpenAIRE

    Soares Neto, Herval Ribeiro; Cavalcante, Wagner Cid Palmeira; Martins Filho, Sebastião Nunes; Smid, Jerusa; Nitrini, Ricardo

    2016-01-01

    We report the case of a patient with insidious onset and slowly progressive cognitive impairment, behavioral symptoms, temporal lobe seizures and delusional thoughts typical of delusional misidentification syndromes. Clinical presentation along with extensive diagnostic work-up revealed limbic encephalitis secondary to diffuse large B-cell lymphoma. The patient underwent immunotherapy with high-dose corticosteroid but no significant improvement was observed. No specific treatment for lymphoma...

  7. 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.

  8. [Diffuse large B-cell lymphoma complicated with drug-induced vasculitis during administration of pegfilgrastim].

    Science.gov (United States)

    Ito, Yuta; Noda, Kentaro; Aiba, Keisuke; Yano, Shingo; Fujii, Tsunehiro

    A 59-year-old female with diffuse large B-cell lymphoma was treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) regimen. In addition, we administered pegfilgrastim for treating chemotherapy-induced febrile neutropenia. She complained of fever and neck and chest pain a few days after pegfilgrastim administration during the third and fourth courses of R-CHOP. Radiological imaging revealed an inflammation of large vessels, which led to the diagnosis of drug-associated vasculitis. We confirmed that vasculitis observed in this case was caused by pegfilgrastim administration because similar symptoms appeared with both injections of pegfilgrastim.

  9. Nuclear criticality safety evaluation of large cylinder cleaning operations in X-705, Portsmouth Gaseous diffusion Plant

    International Nuclear Information System (INIS)

    Sheaffer, M.K.; Keeton, S.C.; Lutz, H.F.

    1995-06-01

    This report evaluates nuclear criticality safety for large cylinder cleaning operations in the Decontamination and Recovery Facility, X-705, at the Portsmouth Gaseous Diffusion Plant. A general description of current cleaning procedures and required hardware/equipment is presented, and documentation for large cylinder cleaning operations is identified and described. Control parameters, design features, administrative controls, and safety systems relevant to nuclear criticality are discussed individually, followed by an overall assessment based on the Double Contingency Principle. Recommendations for enhanced safety are suggested, and issues for increased efficiency are presented

  10. MAGNETIC FIELD STRUCTURE OF THE LARGE MAGELLANIC CLOUD FROM FARADAY ROTATION MEASURES OF DIFFUSE POLARIZED EMISSION

    Energy Technology Data Exchange (ETDEWEB)

    Mao, S. A. [National Radio Astronomy Observatory, P.O. Box O, Socorro, NM 87801 (United States); McClure-Griffiths, N. M.; McConnell, D. [Australia Telescope National Facility, CSIRO Astronomy and Space Science, Epping, NSW 1710 (Australia); Gaensler, B. M. [Sydney Institute for Astronomy, School of Physics, University of Sydney, Sydney, NSW 2006 (Australia); Haverkorn, M. [Department of Astrophysics, Radboud University, P.O. Box 9010, 6500-GL Nijmegen (Netherlands); Beck, R. [Max-Planck-Institut fuer Radioastronomie, D-53121 Bonn (Germany); Wolleben, M. [Square Kilometre Array South Africa, The Park, Pinelands 7405 (South Africa); Stanimirovic, S. [Department of Astronomy, University of Wisconsin, Madison, WI 53706 (United States); Dickey, J. M. [Physics Department, University of Tasmania, Hobart, TAS 7001 (Australia); Staveley-Smith, L., E-mail: mao@astro.wisc.edu [International Centre for Radio Astronomy Research (ICRAR), The University of Western Australia, Crawley, WA 6009 (Australia)

    2012-11-01

    We present a study of the magnetic field of the Large Magellanic Cloud (LMC), carried out using diffuse polarized synchrotron emission data at 1.4 GHz acquired at the Parkes Radio Telescope and the Australia Telescope Compact Array. The observed diffuse polarized emission is likely to originate above the LMC disk on the near side of the galaxy. Consistent negative rotation measures (RMs) derived from the diffuse emission indicate that the line-of-sight magnetic field in the LMC's near-side halo is directed coherently away from us. In combination with RMs of extragalactic sources that lie behind the galaxy, we show that the LMC's large-scale magnetic field is likely to be of quadrupolar geometry, consistent with the prediction of dynamo theory. On smaller scales, we identify two brightly polarized filaments southeast of the LMC, associated with neutral hydrogen arms. The filaments' magnetic field potentially aligns with the direction toward the Small Magellanic Cloud (SMC). We suggest that tidal interactions between the SMC and the LMC in the past 10{sup 9} years are likely to have shaped the magnetic field in these filaments.

  11. Chaotic dynamics of large-scale double-diffusive convection in a porous medium

    Science.gov (United States)

    Kondo, Shutaro; Gotoda, Hiroshi; Miyano, Takaya; Tokuda, Isao T.

    2018-02-01

    We have studied chaotic dynamics of large-scale double-diffusive convection of a viscoelastic fluid in a porous medium from the viewpoint of dynamical systems theory. A fifth-order nonlinear dynamical system modeling the double-diffusive convection is theoretically obtained by incorporating the Darcy-Brinkman equation into transport equations through a physical dimensionless parameter representing porosity. We clearly show that the chaotic convective motion becomes much more complicated with increasing porosity. The degree of dynamic instability during chaotic convective motion is quantified by two important measures: the network entropy of the degree distribution in the horizontal visibility graph and the Kaplan-Yorke dimension in terms of Lyapunov exponents. We also present an interesting on-off intermittent phenomenon in the probability distribution of time intervals exhibiting nearly complete synchronization.

  12. Primary testicular diffuse large B-cell lymphoma: A case report

    Directory of Open Access Journals (Sweden)

    Muhammad Sadiq

    2017-12-01

    Full Text Available Primary testicular diffuse large-B cell lymphoma (DLBCL is an uncommon and aggressive disease with predominant manifestation in the older age. Herein, we report a case of 47-year-old male patient who presented with three months history of left testis swelling. The patient underwent unilateral (left radical orchiectomy. Histopathological examination revealed extensive involvement and replacement of testicular parenchyma by a tumor composed of large discohesive sheets of cells with pleomorphic, hyperchromatic nuclei and prominent nucleoli. Immunohistochemical (IHC staining showed reactivity for LCA & Pan B (CD20 and negativity for OCT 3/4, SALL4 and Inhibin. Moreover, Pan T (CD3 highlighted reactive T-cells. These features rendered the diagnosis of DLBCL of testis. The hybrid 2-[fluorine-18] fluoro-2-deoxy-d-glucose (FDG positron emission tomography/computed tomography (PET/CT demonstrated two para-aortic FDG avid lymph nodes on the left side at the level of L2 vertebra. Presently, the patient has been planned for doxorubicin-based chemotherapy (i.e., cyclophosphamide, doxorubicin, vincristine and prednisone; CHOP along with intrathecal Methroxate (MTX, which would presumably improve the prognosis. Our study would expand the pool of this uncommon tumor towards its better understanding. Keywords: Primary testicular lymphoma, Diffuse large-B cell lymphoma, Orchiectomy, Doxorubicin-based chemotherapy

  13. Grain Boundaries Act as Solid Walls for Charge Carrier Diffusion in Large Crystal MAPI Thin Films.

    Science.gov (United States)

    Ciesielski, Richard; Schäfer, Frank; Hartmann, Nicolai F; Giesbrecht, Nadja; Bein, Thomas; Docampo, Pablo; Hartschuh, Achim

    2018-03-07

    Micro- and nanocrystalline methylammonium lead iodide (MAPI)-based thin-film solar cells today reach power conversion efficiencies of over 20%. We investigate the impact of grain boundaries on charge carrier transport in large crystal MAPI thin films using time-resolved photoluminescence (PL) microscopy and numerical model calculations. Crystal sizes in the range of several tens of micrometers allow for the spatially and time resolved study of boundary effects. Whereas long-ranged diffusive charge carrier transport is observed within single crystals, no detectable diffusive transport occurs across grain boundaries. The observed PL transients are found to crucially depend on the microscopic geometry of the crystal and the point of observation. In particular, spatially restricted diffusion of charge carriers leads to slower PL decay near crystal edges as compared to the crystal center. In contrast to many reports in the literature, our experimental results show no quenching or additional loss channels due to grain boundaries for the studied material, which thus do not negatively affect the performance of the derived thin-film devices.

  14. Global hypomethylation is an independent prognostic factor in diffuse large B cell lymphoma

    DEFF Research Database (Denmark)

    Wedge, Eileen; Hansen, Jakob Werner; Garde, Christian

    2017-01-01

    Global hypomethylation has been linked to disease progression in several cancers, but has not been reported for Diffuse Large B Cell Lymphoma (DLBCL). This study aimed to assess global methylation in DLBCL and describe its prognostic value. Mean LINE1 methylation, a validated surrogate measure...... for global methylation, was measured in DNA from 67 tumor biopsies. Additionally, cell-free circulating DNA (cfDNA) in plasma samples from 74 patients was tested to assess the feasibility of global hypomethylation as a biomarker in liquid biopsies. LINE1 methylation was assessed using a commercially...

  15. Modelling of the diffusion of pollutants in the atmosphere under varying conditions in large cultivated regions

    International Nuclear Information System (INIS)

    Wueneke, C.D.; Schultz, H.

    1975-01-01

    The most important routines of a numerical code based on the particle-in-cell-method for calculating the transport and the turbulent dispersion of inert and radio-active pollutants in the atmosphere have been programmed and have been tested successfully on the CDC computer CYBER 73/76 of the Regional Computer Centre for Niedersachsen in Hanover. Compared to the Gaussian plume model such a numerical code based on the particle-in-cell-method offers several advantages for the computation of the diffusion under varying conditions in large cultivated regions. (orig.) [de

  16. Non-destructive measurement methods for large scale gaseous diffusion process equipment

    International Nuclear Information System (INIS)

    Mayer, R.L.; Hagenauer, R.C.; McGinnis, B.R.

    1994-01-01

    Two measurement methods have been developed to measure non-destructively uranium hold-up in gaseous diffusion plants. These methods include passive neutron and passive γ ray measurements. An additional method, high resolution γ ray spectroscopy, provides supplementary information about additional γ ray emitting isotopes, γ ray correction factors, 235 U/ 234 U ratios and 235 U enrichment. Many of these methods can be used as a general purpose measurement technique for large containers of uranium. Measurement applications for these methods include uranium hold-up, waste measurements, criticality safety and nuclear accountability

  17. Fluorine-18-fluorodeoxyglucose Positron Emission Tomography in Diffuse Large B-cell Lymphoma

    DEFF Research Database (Denmark)

    Mylam, Karen Juul; Nielsen, Anne Lerberg; Pedersen, Lars Møller

    2014-01-01

    Diffuse large B-cell lymphoma (DLBCL) is an aggressive and potentially curable type of lymphoma. Fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) is part of clinical routine for DLBCL in most hospitals and also recommended for staging and end-of-therapy evaluation. FDG......-PET/computed tomography (CT) is able to identify nodal and extranodal sites with greater accuracy than CT alone. Little evidence supports the use of surveillance FDG-PET imaging in the follow-up setting because of high rates of false-positive scans and because most studies are retrospective. This article discusses FDG...

  18. 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...... tumour samples from clinically high risk patients treated in a Nordic phase II study with dose-dense chemoimmunotherapy and central nervous system prophylaxis with high resolution array comparative genomic hybridization (aCGH) and gene expression microarrays. Major finding was validated at the protein...

  19. Systemic diffuse large B-cell lymphoma masquerading as neovascular glaucoma.

    Science.gov (United States)

    Bawankar, Pritam; Das, Dipankar; Bhattacharjee, Harsha; Tayab, Shahinur; Deori, Nilutparna; Paulbuddhe, Vivek; Dhar, Shriya; Deka, Apurba

    2018-02-01

    We describe a case of spontaneous hyphema associated with anterior uveitis presents in a 69-year old female as the prominent sign of the intraocular spread of systemic diffuse large B-cell lymphoma (DLBCL). She had a history of diabetes and initially misdiagnosed as neovascular glaucoma. Clinical history of systemic lymphoma, characteristic findings on B-scan ultrasonography and magnetic resonance imaging scan, and identification of atypical lymphoid cells in aqueous sample established the diagnosis of intraocular metastasis of systemic DLBCL. Therefore, this report highlights that life-threatening malignant systemic lymphoma may masquerade as anterior segment ocular inflammation or neovascular glaucoma.

  20. Treatment of diffuse large B-cell lymphoma of the liver with yttrium-90 microsphere embolization.

    Science.gov (United States)

    Fenske, Timothy S; Benjamin, Heather; Kroft, Steven H; Hohenwalter, Eric J; Rilling, William S

    2008-11-01

    A 41-year-old male with a 4-year history of chronic hepatitis C presented with a 1-month history of abdominal pain, fatigue, weight loss, and night sweats. Laboratory examinations, chest, abdomen, and pelvic CT scans, PET-CT scans, ultrasound-guided needle biopsies of liver lesions, bone-marrow biopsy, flow cytometry, and immunohistochemical staining for B-cell markers including CD20. Chemoresistant diffuse large B-cell lymphoma, with gradual loss of CD20 antigen expression. Embolization of hepatic tumors using yttrium-90 microspheres (Therasphere, Theragenics Corporation, Buford, GA).

  1. Primary diffuse large B cell lymphoma arising from a leiomyoma of the uterine corpus.

    Science.gov (United States)

    Zhao, Lianhua; Ma, Qiang; Wang, Qiushi; Zeng, Ying; Luo, Qingya; Xiao, Hualiang

    2016-01-20

    Primary diffuse large B cell lymphoma (DLBCL) of the uterus is rare, and primary DLBCL arising from a uterine leiomyoma (collision tumor) has not been reported in the literature. We describe the clinical, histological, immunohistochemical, and molecular features of primary DLBCL arising from a leiomyoma in the uterine corpus. A 73-year-old female patient had a uterine mass for 23 years. An ultrasound scan revealed marked enlargement of the uterus, measuring 18.2 × 13 × 16.3 cm, with a 17.6 × 10.9 × 11.6 cm hypoechoic mass in the uterine corpus. The tumors consisted of medium- to large-sized cells exhibiting a diffuse pattern of growth with a well-circumscribed leiomyoma. The neoplastic cells strongly expressed CD79α, CD20 and PAX5. Molecular analyses indicated clonal B-cell receptor gene rearrangement. To the best of our knowledge, no previous cases of primary DLBCL arising from a leiomyoma have been reported. It is necessary to differentiate a diagnosis of primary DLBCL arising from a leiomyoma from that of leiomyoma with florid reactive lymphocytic infiltration (lymphoma-like lesion). Careful analysis of clinical, histological, immunophenotypic, and genetic features is required to establish the correct diagnosis.

  2. Orbital diffuse large B-cell lymphoma with combined variable immunodeficiency.

    Science.gov (United States)

    Parikh, Vishal S; Jagadeesh, Deepa; Fernandez, James M; Hsi, Eric D; Singh, Arun D

    2017-10-01

    Common variable immunodeficiency (CVID) is a primary immunodeficiency manifesting as a reduction in the level of total immunoglobulin (Ig) G, a reduction in the level of either IgA or IgM, poor response to polysaccharide vaccine, and usually frequent infections. The association of CVID with an increased risk of malignancy, specifically lymphoma, is well known. A 63-year-old female with a past medical history significant for CVID presented with a 1-month history of dull, left eye pain with proptosis, hypoglobus, and left upper lid fullness without a discrete palpable mass. Magnetic resonance imaging (MRI) of the orbits revealed a diffuse infiltrating orbital mass superonasally with extension into the superior rectus muscle, medial rectus muscle, and optic nerve up to the orbital apex and ethmoid sinus. A superonasal orbital biopsy with a caruncular approach was performed and demonstrated a sparse lymphoid infiltrate that was suggestive for a large B-cell neoplasm. Positron emission tomography (PET) scan demonstrated a hypermetabolic right lymph node, anterior to the right submandibular gland, which was biopsied and histopathology confirmed diffuse large B-cell lymphoma (DLBCL). Our patient achieved a very good response to chemotherapy with minimal residual disease on PET scan at the end of treatment. She attained a complete remission after radiation therapy. In conclusion, patients with new orbital and adnexa masses in the setting of a primary immunodeficiency can have an aggressive malignancy such as DLBCL and early diagnosis and systemic treatment carries a good prognosis.

  3. Spontaneous regression of primary diffuse large B-cell lymphoma, leg type.

    Science.gov (United States)

    Alcántara-González, J; González-García, C; Fernández-Guarino, M; Jaén-Olasolo, P

    2014-01-01

    Primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL LT) accounts for approximately 20% of all primary cutaneous B-cell lymphomas and tends to present as infiltrated nodules, tumors, and plaques on the legs in the elderly. Unlike other primary cutaneous large B-cell lymphomas, it has a poor prognosis and tends to require treatment with systemic chemotherapy. We present the case of an 82-year-old patient with a 1-year history of nodules and plaques on her right leg. Biopsy led to a diagnosis of PCLBCL LT and the lesions resolved without treatment within 1 month of the first visit. This is an atypical course of PCLBCL LT and we believe that it is the first such case to be reported in the literature. Copyright © 2012 Elsevier España, S.L. and AEDV. All rights reserved.

  4. Chidamide Combined With R-GDP in Treating Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma (DLBCL)

    Science.gov (United States)

    2017-12-12

    Chidamide; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Neoplasm by Histology; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin; Cyclophosphamide; Rituximab; Gemcitabine; Cisplatin; Dexamethasone; HDAC Inhibitor

  5. Pituitary and adrenal involvement in diffuse large B-cell lymphoma, with recovery of their function after chemotherapy

    OpenAIRE

    Nakashima, Yasuhiro; Shiratsuchi, Motoaki; Abe, Ichiro; Matsuda, Yayoi; Miyata, Noriyuki; Ohno, Hirofumi; Ikeda, Motohiko; Matsushima, Takamitsu; Nomura, Masatoshi; Takayanagi, Ryoichi

    2013-01-01

    Background Diffuse large B-cell lymphoma sometimes involves the endocrine organs, but involvement of both the pituitary and adrenal glands is extremely rare. Involvement of these structures can lead to hypopituitarism and adrenal insufficiency, and subsequent recovery of their function is rarely seen. The present report describes an extremely rare case of pituitary and adrenal diffuse large B-cell lymphoma presenting with hypopituitarism and adrenal insufficiency with subsequent recovery of p...

  6. 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.

  7. Primary Cutaneous Diffuse Large B-Cell Lymphoma – a Case Report

    Directory of Open Access Journals (Sweden)

    Milovanović Milena

    2017-06-01

    Full Text Available In 2005, the World Health Organization - European Organization for Research and Treatment of Cancer (WHOEORTC classified cutaneous B-cell lymphomas into 4 categories: primary cutaneous marginal zone B-cell lymphoma (PCMZL, primary cutaneous follicle center lymphoma (PCFCL, primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT, and primary cutaneous diffuse large B-cell lymphoma, other (PCDLBCL-O. The absence of evident extra-cutaneous disease is a necessary condition for the diagnosis of primary cutaneous B-cell lymphomas, because they have a completely different clinical behavior and prognosis from their nodal counterparts. PCDLBCL-O basically represents a morphological variation, lacking the typical features of PCDLBCLLT, neither confirming the definition of PCFCCL, but on the clinical ground, its behavior seems at least to partially overlap the indolent course of PCFCCL. In fact, the present WHO lymphoma classification from 2008 overcame the previous WHO-EORTC classification, including at least a part of PCDLBCL-O within the spectrum of PCFCCL. However, owing to the rarity and heterogeneity of the PCDLBCL-O, the precise clinicopathological characteristics have not been well characterized and the optimal treatment for this group of lymphomas is yet to be defined. Nevertheless, dermatologists and pathologists should be aware of this entity in order to avoid unnecessary aggressive treatment. We present a case of a 46-year-old Caucasian male with one large round-shaped tumor and a few scattered nodules localized on the back. The histopathological features of the lesion corresponded to PCDLBCL-O. The patient follow-up showed that he was disease-free three months after surgical excision of the lesions and adjuvant local radiotherapy. No additional therapy was introduced, including chemotherapy with rituximab, cyclophosphamide, doxorubicin hydrochloride, oncovin, prednisolone (R-CHOP.

  8. Evaluating neighborhood structures for modeling intercity diffusion of large-scale dengue epidemics.

    Science.gov (United States)

    Wen, Tzai-Hung; Hsu, Ching-Shun; Hu, Ming-Che

    2018-05-03

    Dengue fever is a vector-borne infectious disease that is transmitted by contact between vector mosquitoes and susceptible hosts. The literature has addressed the issue on quantifying the effect of individual mobility on dengue transmission. However, there are methodological concerns in the spatial regression model configuration for examining the effect of intercity-scale human mobility on dengue diffusion. The purposes of the study are to investigate the influence of neighborhood structures on intercity epidemic progression from pre-epidemic to epidemic periods and to compare definitions of different neighborhood structures for interpreting the spread of dengue epidemics. We proposed a framework for assessing the effect of model configurations on dengue incidence in 2014 and 2015, which were the most severe outbreaks in 70 years in Taiwan. Compared with the conventional model configuration in spatial regression analysis, our proposed model used a radiation model, which reflects population flow between townships, as a spatial weight to capture the structure of human mobility. The results of our model demonstrate better model fitting performance, indicating that the structure of human mobility has better explanatory power in dengue diffusion than the geometric structure of administration boundaries and geographic distance between centroids of cities. We also identified spatial-temporal hierarchy of dengue diffusion: dengue incidence would be influenced by its immediate neighboring townships during pre-epidemic and epidemic periods, and also with more distant neighbors (based on mobility) in pre-epidemic periods. Our findings suggest that the structure of population mobility could more reasonably capture urban-to-urban interactions, which implies that the hub cities could be a "bridge" for large-scale transmission and make townships that immediately connect to hub cities more vulnerable to dengue epidemics.

  9. Quantitative diffusion and swelling kinetic measurements using large-angle interferometric refractometry.

    Science.gov (United States)

    Saunders, John E; Chen, Hao; Brauer, Chris; Clayton, McGregor; Chen, Weijian; Barnes, Jack A; Loock, Hans-Peter

    2015-12-07

    The uptake and release of sorbates into films and coatings is typically accompanied by changes of the films' refractive index and thickness. We provide a comprehensive model to calculate the concentration of the sorbate from the average refractive index and the film thickness, and validate the model experimentally. The mass fraction of the analyte partitioned into a film is described quantitatively by the Lorentz-Lorenz equation and the Clausius-Mosotti equation. To validate the model, the uptake kinetics of water and other solvents into SU-8 films (d = 40-45 μm) were explored. Large-angle interferometric refractometry measurements can be used to characterize films that are between 15 μm to 150 μm thick and, Fourier analysis, is used to determine independently the thickness, the average refractive index and the refractive index at the film-substrate interface at one-second time intervals. From these values the mass fraction of water in SU-8 was calculated. The kinetics were best described by two independent uptake processes having different rates. Each process followed one-dimensional Fickian diffusion kinetics with diffusion coefficients for water into SU-8 photoresist film of 5.67 × 10(-9) cm(2) s(-1) and 61.2 × 10(-9) cm(2) s(-1).

  10. 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.

  11. A Case of Diffuse Large B-Cell Lymphoma Mimicking Primary Effusion Lymphoma-Like Lymphoma

    Directory of Open Access Journals (Sweden)

    Daisuke Usuda

    2017-11-01

    Full Text Available A 93-year-old female was transferred to the emergency ward of our hospital due to disturbance of consciousness and hypotension. Computed tomography showed bilateral pleural and pericardial effusion without evidence of tumor masses or lymphadenopathy. Cytodiagnosis of pleural effusion revealed proliferation of atypical lymphoid-like cells with pan-B surface markers. We suspected primary effusion lymphoma-like lymphoma; however, the monoclonality of these cells was not confirmed. Cytodiagnosis of bone marrow revealed lymphoma cells with monoclonal B-cell markers. These findings prompted a diagnosis of diffuse large B-cell lymphoma with bone marrow invasion. In the case of pericardial or pleural effusion, clinicians should consider carefully both hematological malignancy and its classification.

  12. Diffuse large B-cell lymphoma in the era of precision oncology: How imaging is helpful

    Energy Technology Data Exchange (ETDEWEB)

    Shah, Hina J.; Keraliya, Abhishek R.; Lele, Vikram R.; Tirumani, Sree Harsha; DiPiro, Pamela J.; Jagannathan, Jyothi P. [Dept. of Imaging, Dana Farber Cancer Institute, Harvard Medical School, Boston (United States)

    2017-01-15

    Diffuse large B cell lymphoma (DLBCL) is the most common histological subtype of Non-Hodgkin's lymphoma. As treatments continues to evolve, so do imaging strategies, and positron emission tomography (PET) has emerged as the most important imaging tool to guide oncologists in the diagnosis, staging, response assessment, relapse/recurrence detection,and therapeutic decision making of DLBCL. Other imaging modalities including magnetic resonance imaging (MRI), computed tomography (CT), ultrasound, and conventional radiography are also used in the evaluation of lymphoma. MRI is useful for nervous system and musculoskeletal system involvement and is emerging as a radiation free alternative to PET/CT. This article provides a comprehensive review of both the functional and morphological imaging modalities, available in the management of DLBCL.

  13. Highly-sensitive and large-dynamic diffuse optical tomography system for breast tumor detection

    Science.gov (United States)

    Du, Wenwen; Zhang, Limin; Yin, Guoyan; Zhang, Yanqi; Zhao, Huijuan; Gao, Feng

    2018-02-01

    Diffuse optical tomography (DOT) as a new functional imaging has important clinical applications in many aspects such as benign and malignant breast tumor detection, tumor staging and so on. For quantitative detection of breast tumor, a three-wavelength continuous-wave DOT prototype system combined the ultra-high sensitivity of the photon-counting detection and the measurement parallelism of the lock-in technique was developed to provide high temporal resolution, high sensitivity, large dynamic detection range and signal-to-noise ratio. Additionally, a CT-analogous scanning mode was proposed to cost-effectively increase the detection data. To evaluate the feasibility of the system, a series of assessments were conducted. The results demonstrate that the system can obtain high linearity, stability and negligible inter-wavelength crosstalk. The preliminary phantom experiments show the absorption coefficient is able to be successfully reconstructed, indicating that the system is one of the ideal platforms for optical breast tumor detection.

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

    DEFF Research Database (Denmark)

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

    2005-01-01

    on the Affymetrix HG-U133A oligonucleotide arrays and improve the classification, we determined the expression profiles of pretreatment, diagnostic samples from 52 primary nodal DLBCL. METHODS AND RESULTS: First, three previously published gene lists were converted to the HG-U133A probe sets and used......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...... for hierarchical clustering. In this way, three subtypes, including the GCB type (n = 20), the ABC type (n = 25) and an intermediate group, Type-3 (n = 5), were distinguished. The CD10 and Bcl-6 expression as well as t(14;18) translocation were prevalent, but not exclusive to the GCB type. By contrast, MUM1...

  15. High density high performance plasma with internal diffusion barrier in Large Helical Device

    International Nuclear Information System (INIS)

    Sakamoto, R.; Kobayashi, M.; Miyazawa, J.

    2008-10-01

    A attractive high density plasma operational regime, namely an internal diffusion barrier (IDB), has been discovered in the intrinsic helical divertor configuration on the Large Helical Device (LHD). The IDB which enables core plasma to access a high density/high pressure regime has been developed. It is revealed that the IDB is reproducibly formed by pellet fueling in the magnetic configurations shifted outward in major radius. Attainable central plasma density exceeds 1x10 21 m -3 . Central pressure reaches 1.5 times atmospheric pressure and the central β value becomes fairly high even at high magnetic field, i.e. β(0)=5.5% at B t =2.57 T. (author)

  16. Conditional survival of patients with diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Møller, Michael Boe; Pedersen, Niels Tinggaard; Christensen, Bjarne E

    2006-01-01

    BACKGROUND: Prognosis of lymphoma patients is usually estimated at the time of diagnosis and the estimates are guided by the International Prognostic Index (IPI). However, conditional survival estimates are more informative clinically, as they consider those patients only who have already survive...... survival probability provides more accurate prognostic information than the conventional survival rate estimated from the time of diagnosis.......BACKGROUND: Prognosis of lymphoma patients is usually estimated at the time of diagnosis and the estimates are guided by the International Prognostic Index (IPI). However, conditional survival estimates are more informative clinically, as they consider those patients only who have already survived...... a period of time after treatment. Conditional survival data have not been reported for lymphoma patients. METHODS: Conditional survival was estimated for 1209 patients with diffuse large B-cell lymphoma (DLBCL) from the population-based LYFO registry of the Danish Lymphoma Group. The Kaplan-Meier method...

  17. Survival in patients with oral and maxillofacial diffuse large B-cell lymphoma

    Directory of Open Access Journals (Sweden)

    Janet Ofelia Guevara-Canales

    2013-11-01

    Full Text Available The purpose of this study was to determine the survival and prognostic factors of patients with diffuse large B-cell lymphoma (DLBCL of the oral cavity and maxillofacial region. Retrospectively, the clinical records of patients with a primary diagnosis of DLBCL of the oral cavity and maxillofacial region treated at the A.C. Camargo Hospital for Cancer, São Paulo, Brazil, between January 1980 and December 2005 were evaluated to determine (A overall survival (OS at 2 and 5 years and the individual survival percentage for each possible prognostic factor by means of the actuarial technique (also known as mortality tables, and the Kaplan Meier product limit method (which provided the survival value curves for each possible prognostic factor; (B prognostic factors subject to univariate evaluation with the log-rank test (also known as Mantel-Cox, and multivariate analysis with Cox's regression model (all the variables together. The data were considered significant at p ≤ 0.05. From 1980 to 2005, 3513 new cases of lymphomas were treated, of which 151 (4.3% occurred in the oral cavity and maxillofacial region. Of these 151 lesions, 48 were diffuse large B-cell lymphoma, with 64% for OS at 2 years and 45% for OS at 5 years. Of the variables studied as possible prognostic factors, multivariate analysis found the following variables have statistically significant values: age (p = 0.042, clinical stage (p = 0.007 and performance status (p = 0.031. These data suggest that patients have a higher risk of mortality if they are older, at a later clinical stage, and have a higher performance status.

  18. 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

  19. Strong motion modeling at the Paducah Diffusion Facility for a large New Madrid earthquake

    International Nuclear Information System (INIS)

    Herrmann, R.B.

    1991-01-01

    The Paducah Diffusion Facility is within 80 kilometers of the location of the very large New Madrid earthquakes which occurred during the winter of 1811-1812. Because of their size, seismic moment of 2.0 x 10 27 dyne-cm or moment magnitude M w = 7.5, the possible recurrence of these earthquakes is a major element in the assessment of seismic hazard at the facility. Probabilistic hazard analysis can provide uniform hazard response spectra estimates for structure evaluation, but a deterministic modeling of a such a large earthquake can provide strong constraints on the expected duration of motion. The large earthquake is modeled by specifying the earthquake fault and its orientation with respect to the site, and by specifying the rupture process. Synthetic time histories, based on forward modeling of the wavefield, from each subelement are combined to yield a three component time history at the site. Various simulations are performed to sufficiently exercise possible spatial and temporal distributions of energy release on the fault. Preliminary results demonstrate the sensitivity of the method to various assumptions, and also indicate strongly that the total duration of ground motion at the site is controlled primarily by the length of the rupture process on the fault

  20. Diffusion Experiments with Opalinus and Callovo-Oxfordian Clays: Laboratory, Large-Scale Experiments and Microscale Analysis by RBS

    International Nuclear Information System (INIS)

    Garcia-Gutierrez, M.; Alonso, U.; Missana, T.; Cormenzana, J.L.; Mingarro, M.; Morejon, J.; Gil, P.

    2009-01-01

    Consolidated clays are potential host rocks for deep geological repositories for high-level radioactive waste. Diffusion is the main transport process for radionuclides (RN) in these clays. Radionuclide (RN) diffusion coefficients are the most important parameters for Performance Assessment (PA) calculations of clay barriers. Different diffusion methodologies were applied at a laboratory scale to analyse the diffusion behaviour of a wide range of RN. Main aims were to understand the transport properties of different RNs in two different clays and to contribute with feasible methodologies to improve in-situ diffusion experiments, using samples of larger scale. Classical laboratory essays and a novel experimental set-up for large-scale diffusion experiments were performed, together to a novel application of the nuclear ion beam technique Rutherford Backscattering Spectrometry (RBS), for diffusion analyses at the micrometer scale. The main experimental and theoretical characteristics of the different methodologies, and their advantages and limitations are here discussed. Experiments were performed with the Opalinus and the Callovo-Oxfordian clays. Both clays are studied as potential host rock for a repository. Effective diffusion coefficients ranged between 1.10 - 10 to 1.10 - 12 m 2 /s for neutral, low sorbing cations (as Na and Sr) and anions. Apparent diffusion coefficients for strongly sorbing elements, as Cs and Co, are in the order of 1.10-13 m 2 /s; europium present the lowest diffusion coefficient (5.10 - 15 m 2 /s). The results obtained by the different approaches gave a comprehensive database of diffusion coefficients for RN with different transport behaviour within both clays. (Author) 42 refs

  1. Diffusion Experiments with Opalinus and Callovo-Oxfordian Clays: Laboratory, Large-Scale Experiments and Microscale Analysis by RBS

    Energy Technology Data Exchange (ETDEWEB)

    Garcia-Gutierrez, M.; Alonso, U.; Missana, T.; Cormenzana, J.L.; Mingarro, M.; Morejon, J.; Gil, P.

    2009-09-25

    Consolidated clays are potential host rocks for deep geological repositories for high-level radioactive waste. Diffusion is the main transport process for radionuclides (RN) in these clays. Radionuclide (RN) diffusion coefficients are the most important parameters for Performance Assessment (PA) calculations of clay barriers. Different diffusion methodologies were applied at a laboratory scale to analyse the diffusion behaviour of a wide range of RN. Main aims were to understand the transport properties of different RNs in two different clays and to contribute with feasible methodologies to improve in-situ diffusion experiments, using samples of larger scale. Classical laboratory essays and a novel experimental set-up for large-scale diffusion experiments were performed, together to a novel application of the nuclear ion beam technique Rutherford Backscattering Spectrometry (RBS), for diffusion analyses at the micrometer scale. The main experimental and theoretical characteristics of the different methodologies, and their advantages and limitations are here discussed. Experiments were performed with the Opalinus and the Callovo-Oxfordian clays. Both clays are studied as potential host rock for a repository. Effective diffusion coefficients ranged between 1.10{sup -}10 to 1.10{sup -}12 m{sup 2}/s for neutral, low sorbing cations (as Na and Sr) and anions. Apparent diffusion coefficients for strongly sorbing elements, as Cs and Co, are in the order of 1.10-13 m{sup 2}/s; europium present the lowest diffusion coefficient (5.10{sup -}15 m{sup 2}/s). The results obtained by the different approaches gave a comprehensive database of diffusion coefficients for RN with different transport behaviour within both clays. (Author) 42 refs.

  2. Diffuse stenotic change in large intracranial arteries following irradiation therapy for medulloblastoma

    International Nuclear Information System (INIS)

    Yamakami, Iwao; Sugaya, Yuichi; Sato, Masanori; Osato, Katunobu; Yamaura, Akira; Makino, Hiroyasu.

    1990-01-01

    We reported a case of a patient who developed a diffuse stenotic change in the large intracranial arteries and repeated episodes of cerebral infarction after irradiation therapy for medulloblastoma. A three-year-old girl underwent the subtotal removal of cerebellar medulloblastoma and the subsequent irradiation therapy in the whole brain and spine (30 Gy in the whole brain, 20 Gy in the local brain, and 25 Gy in the whole spine). Two years later, she again underwent surgery and irradiation therapy because a recurrence of medulloblastoma had manifested itself in the frontal lobe; (40 Gy in the whole brain, 20 Gy in the local brain, and 25 Gy in the whole spine). One and half years after the second irradiation, she started suffering from frequent and refractory cerebral ischemic attacks. Cerebral angiography revealed a diffuse narrowing, and multifocal stenoses in the bilateral anterior and middle cerebral arteries. Computerized tomography demonstrated multiple cerebral infarctions. Her neurological condition deteriorated because of recurring strokes and she died at ten years of age. Most of the reported cases of patients who developed stenotic arteriopathy were children in the first decade of their life, and who were irradiated for parasellar brain tumor of low malignancy. Stenotic arteriopathy after irradiation has rarely been recognized in patients with malignant brain tumor. However, life expectancy is increasing even for those with malignant brain tumor, and it may make stenotic arteriopathy after irradiation recognized more commonly in patients with malignant brain tumor. Careful irradiation and subsequent angiographical examination should be required even in patients with malignant brain tumor. (author)

  3. A Case of Successful Remission of Extensive Primary Gastric Diffuse Large B Cell Lymphoma: Radiologic, Endoscopic and Pathologic Evidence

    Directory of Open Access Journals (Sweden)

    Mike M. Bismar

    2014-04-01

    Full Text Available Though rare amongst stomach neoplasms, primary gastric diffuse large B cell lymphoma is one of the commonest extranodal non-Hodgkin lymphomas. If left untreated, it can have a devastating progression and life-threatening consequences. We present the case of a successfully treated large antral ulcer confirmed to be large B cell lymphoma as evidenced by radiologic, endoscopic and histopathologic findings. A brief discussion about the types of gastric lymphoma, their Helicobacter pylori relation and therapeutic modalities follows.

  4. Prognostic impact of concurrent MYC and BCL6 rearrangements and expression in de novo diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Ye, Qing; Xu-Monette, Zijun Y; Tzankov, Alexandar

    2016-01-01

    Double-hit B-cell lymphoma is a common designation for a group of tumors characterized by concurrent translocations of MYC and BCL2, BCL6, or other genes. The prognosis of concurrent MYC and BCL6 translocations is not well known. In this study, we assessed rearrangements and expression of MYC, BCL2...... frequent in activated B-cell like diffuse large B-cell lymphoma). In summary, diffuse large B-cell lymphoma patients with either MYC/BCL6 rearrangements or MYC/BCL6 co-expression did not always have poorer prognosis; MYC expression levels should be evaluated simultaneously; and double-hit B-cell lymphoma...

  5. Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes.

    Science.gov (United States)

    Chapuy, Bjoern; Stewart, Chip; Dunford, Andrew J; Kim, Jaegil; Kamburov, Atanas; Redd, Robert A; Lawrence, Mike S; Roemer, Margaretha G M; Li, Amy J; Ziepert, Marita; Staiger, Annette M; Wala, Jeremiah A; Ducar, Matthew D; Leshchiner, Ignaty; Rheinbay, Ester; Taylor-Weiner, Amaro; Coughlin, Caroline A; Hess, Julian M; Pedamallu, Chandra S; Livitz, Dimitri; Rosebrock, Daniel; Rosenberg, Mara; Tracy, Adam A; Horn, Heike; van Hummelen, Paul; Feldman, Andrew L; Link, Brian K; Novak, Anne J; Cerhan, James R; Habermann, Thomas M; Siebert, Reiner; Rosenwald, Andreas; Thorner, Aaron R; Meyerson, Matthew L; Golub, Todd R; Beroukhim, Rameen; Wulf, Gerald G; Ott, German; Rodig, Scott J; Monti, Stefano; Neuberg, Donna S; Loeffler, Markus; Pfreundschuh, Michael; Trümper, Lorenz; Getz, Gad; Shipp, Margaret A

    2018-04-30

    Diffuse large B cell lymphoma (DLBCL), the most common lymphoid malignancy in adults, is a clinically and genetically heterogeneous disease that is further classified into transcriptionally defined activated B cell (ABC) and germinal center B cell (GCB) subtypes. We carried out a comprehensive genetic analysis of 304 primary DLBCLs and identified low-frequency alterations, captured recurrent mutations, somatic copy number alterations, and structural variants, and defined coordinate signatures in patients with available outcome data. We integrated these genetic drivers using consensus clustering and identified five robust DLBCL subsets, including a previously unrecognized group of low-risk ABC-DLBCLs of extrafollicular/marginal zone origin; two distinct subsets of GCB-DLBCLs with different outcomes and targetable alterations; and an ABC/GCB-independent group with biallelic inactivation of TP53, CDKN2A loss, and associated genomic instability. The genetic features of the newly characterized subsets, their mutational signatures, and the temporal ordering of identified alterations provide new insights into DLBCL pathogenesis. The coordinate genetic signatures also predict outcome independent of the clinical International Prognostic Index and suggest new combination treatment strategies. More broadly, our results provide a roadmap for an actionable DLBCL classification.

  6. [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. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  7. CD79B limits response of diffuse large B cell lymphoma to ibrutinib.

    Science.gov (United States)

    Kim, Joo Hyun; Kim, Won Seog; Ryu, Kyungju; Kim, Seok Jin; Park, Chaehwa

    2016-01-01

    Blockage of B cell receptor signaling with ibrutinib presents a promising clinical approach for treatment of B-cell malignancies. However, many patients show primary resistance to the drug or develop secondary resistance. In the current study, cDNA microarray and Western blot analyses revealed CD79B upregulation in the activated B cell-like diffuse large B-cell lymphoma (ABC-DLBCL) that display differential resistance to ibrutinib. CD79B overexpression was sufficient to induce resistance to ibrutinib and enhanced AKT and MAPK activation, indicative of an alternative mechanism underlying resistance. Conversely, depletion of CD79B sensitized primary refractory cells to ibrutinib and led to reduced phosphorylation of AKT or MAPK. Combination of the AKT inhibitor or the MAPK inhibitor with ibrutinib resulted in circumvention of both primary and acquired resistance in ABC-DLBCL. Our data collectively indicate that CD79B overexpression leading to activation of AKT/MAPK is a potential mechanism underlying primary ibrutinib resistance in ABC-DLBCL, and support its utility as an effective biomarker to predict therapeutic response to ibrutinib.

  8. Combination of Ibrutinib and ABT-199 in Diffuse Large B-Cell Lymphoma and Follicular Lymphoma.

    Science.gov (United States)

    Kuo, Hsu-Ping; Ezell, Scott A; Schweighofer, Karl J; Cheung, Leo W K; Hsieh, Sidney; Apatira, Mutiah; Sirisawad, Mint; Eckert, Karl; Hsu, Ssucheng J; Chen, Chun-Te; Beaupre, Darrin M; Versele, Matthias; Chang, Betty Y

    2017-07-01

    Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma are the most prevalent B-lymphocyte neoplasms in which abnormal activation of the Bruton tyrosine kinase (BTK)-mediated B-cell receptor signaling pathway contributes to pathogenesis. Ibrutinib is an oral covalent BTK inhibitor that has shown some efficacy in both indications. To improve ibrutinib efficacy through combination therapy, we first investigated differential gene expression in parental and ibrutinib-resistant cell lines to better understand the mechanisms of resistance. Ibrutinib-resistant TMD8 cells had higher BCL2 gene expression and increased sensitivity to ABT-199, a BCL-2 inhibitor. Consistently, clinical samples from ABC-DLBCL patients who experienced poorer response to ibrutinib had higher BCL2 gene expression. We further demonstrated synergistic growth suppression by ibrutinib and ABT-199 in multiple ABC-DLBCL, GCB-DLBCL, and follicular lymphoma cell lines. The combination of both drugs also reduced colony formation, increased apoptosis, and inhibited tumor growth in a TMD8 xenograft model. A synergistic combination effect was also found in ibrutinib-resistant cells generated by either genetic mutation or drug treatment. Together, these findings suggest a potential clinical benefit from ibrutinib and ABT-199 combination therapy. Mol Cancer Ther; 16(7); 1246-56. ©2017 AACR . ©2017 American Association for Cancer Research.

  9. Central nervous system prophylaxis in diffuse large B-cell lymphoma.

    Science.gov (United States)

    Zahid, Mohammad Faizan; Khan, Nadia; Hashmi, Shahrukh K; Kizilbash, Sani Haider; Barta, Stefan K

    2016-08-01

    Central nervous system (CNS) involvement with diffuse large B-cell lymphoma (DLBCL) is a relatively uncommon manifestation; with most cases of CNS involvement occuring during relapse after primary therapy. CNS dissemination typically occurs early in the disease course and is most likely present subclinically at the time of diagnosis in many patients who later relapse in the CNS. CNS relapse in these patients is associated with poor outcomes. Based on a CNS relapse rate of 5% in DLBCL and weighing the benefits against the toxicities, universal application of CNS prophylaxis is not justified. The introduction of rituximab has significantly reduced the incidence of CNS relapse in DLBCL. Different studies have employed other agents for CNS prophylaxis, such as intrathecal chemotherapy and high-dose systemic agents with sufficient CNS penetration. If CNS prophylaxis is to be given, it should be preferably administered during primary chemotherapy. However, there is no strong evidence that supports any single approach for CNS prophylaxis. In this review, we outline different strategies of administering CNS prophylaxis in DLBCL patients reported in literature and discuss their advantages and drawbacks. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Discovery of large-scale diffuse radio emission in low-mass galaxy cluster Abell 1931

    Science.gov (United States)

    Brüggen, M.; Rafferty, D.; Bonafede, A.; van Weeren, R. J.; Shimwell, T.; Intema, H.; Röttgering, H.; Brunetti, G.; Di Gennaro, G.; Savini, F.; Wilber, A.; O'Sullivan, S.; Ensslin, T. A.; De Gasperin, F.; Hoeft, M.

    2018-04-01

    Extended, steep-spectrum radio synchrotron sources are pre-dominantly found in massive galaxy clusters as opposed to groups. LOFAR Two-Metre Sky Survey images have revealed a diffuse, ultra-steep spectrum radio source in the low-mass cluster Abell 1931. The source has a fairly irregular morphology with a largest linear size of about 550 kpc. The source is only seen in LOFAR observations at 143 MHz and GMRT observations at 325 MHz. The spectral index of the total source between 143 MHz and 325 MHz is α _{143}^{325} = -2.86 ± 0.36. The source remains invisible in Very Large Array (1-2 GHz) observations as expected given the spectral index. Chandra X-ray observations of the cluster revealed a bolometric luminosity of LX = (1.65 ± 0.39) × 1043 erg s-1 and a temperature of 2.92_{-0.87}^{+1.89} keV which implies a mass of around ˜1014M⊙. We conclude that the source is a remnant radio galaxy that has shut off around 200 Myr ago. The brightest cluster galaxy, a radio-loud elliptical galaxy, could be the source for this extinct source. Unlike remnant sources studied in the literature, our source has a steep spectrum at low radio frequencies. Studying such remnant radio galaxies at low radio frequencies is important for understanding the scarcity of such sources and their role in feedback processes.

  11. Intestinal diffuse large B-cell lymphoma: an evaluation of different staging systems.

    Science.gov (United States)

    Hwang, Hee Sang; Yoon, Dok Hyun; Suh, Cheolwon; Park, Chan-Sik; Huh, Jooryung

    2014-01-01

    The gastrointestinal tract is the most common primary extranodal site for diffuse large B-cell lymphoma (DLBCL). However, there is no consensus on the most appropriate staging system for intestinal DLBCL. We evaluated the utility of the modified Ann Arbor system, the Lugano system, and the Paris staging system (a modification of the Tumor, Node, Metastases [TNM] staging for epithelial tumors) in 66 cases of resected intestinal DLBCL. The cases were treated with surgery, plus either cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) chemotherapy alone (n=26) or with the addition of rituximab immunotherapy (n=40). Median follow-up time was 40.4 months (range, 2.1-171.6 months). Fifty-six patients (84.8%) achieved complete remission. The overall 5-yr survival rate was 86.4% (57/66). Of the stage categories defined for each staging system, only the T stage of the Paris classification showed prognostic significance for overall survival by univariate analysis. However, none of the stage parameters was significantly correlated with patient survival on multivariate analysis. In conclusion, the results suggest that the T stage of the Paris classification system may be a prognostic indicator in intestinal DLBCL. The results also imply that in surgically resected intestinal DLBCL, the addition of rituximab to the CHOP regimen does not confer significant survival advantage.

  12. A Diffuse Interface Model for Incompressible Two-Phase Flow with Large Density Ratios

    KAUST Repository

    Xie, Yu; Wodo, Olga; Ganapathysubramanian, Baskar

    2016-01-01

    In this chapter, we explore numerical simulations of incompressible and immiscible two-phase flows. The description of the fluid–fluid interface is introduced via a diffuse interface approach. The two-phase fluid system is represented by a coupled Cahn–Hilliard Navier–Stokes set of equations. We discuss challenges and approaches to solving this coupled set of equations using a stabilized finite element formulation, especially in the case of a large density ratio between the two fluids. Specific features that enabled efficient solution of the equations include: (i) a conservative form of the convective term in the Cahn–Hilliard equation which ensures mass conservation of both fluid components; (ii) a continuous formula to compute the interfacial surface tension which results in lower requirement on the spatial resolution of the interface; and (iii) a four-step fractional scheme to decouple pressure from velocity in the Navier–Stokes equation. These are integrated with standard streamline-upwind Petrov–Galerkin stabilization to avoid spurious oscillations. We perform numerical tests to determine the minimal resolution of spatial discretization. Finally, we illustrate the accuracy of the framework using the analytical results of Prosperetti for a damped oscillating interface between two fluids with a density contrast.

  13. Novel disease targets and management approaches for diffuse large B-cell lymphoma.

    Science.gov (United States)

    Wilson, Wyndham H; Hernandez-Ilizaliturri, Francisco J; Dunleavy, Kieron; Little, Richard F; O'Connor, Owen A

    2010-08-01

    Diffuse large B-cell lymphoma (DLBCL) responds well to treatment with CHOP and the R-CHOP regimen, but a subset of patients still fail to achieve complete or durable responses. Recent advances in gene expression profiling have led to the identification of three different subtypes of DLBCL, and confirmed that patients with the activated B-cell (ABC) disease subtype are less likely to respond well to CHOP-based regimens than those with germinal centre B-cell-type (GCB) disease. This discovery could herald the use of gene expression profiling to aid treatment decisions in DLBCL, and help identify the most effective management strategies for patients. Treatment options for patients with relapsed or refractory DLBCL are limited and several novel agents are being developed to address this unmet clinical need. Novel agents developed to treat plasma cell disorders such as multiple myeloma have shown promising activity in patients with NHL. Indeed, the immunomodulatory agent lenalidomide and the proteasome inhibitors bortezomib and carfilzomib, as single agents or in combination with chemotherapy, have already demonstrated promising activity in patients with the ABC subtype of DLBCL. One should not be complacent however when applying these agents to new disease types, because dose and drug scheduling can have marked effects on the responses achieved with investigational agents. As more targeted agents are developed, the timing of administration with other agents in clinical trials will become increasingly important to ensure maximal efficacy while minimizing side effects.

  14. A Diffuse Interface Model for Incompressible Two-Phase Flow with Large Density Ratios

    KAUST Repository

    Xie, Yu

    2016-10-04

    In this chapter, we explore numerical simulations of incompressible and immiscible two-phase flows. The description of the fluid–fluid interface is introduced via a diffuse interface approach. The two-phase fluid system is represented by a coupled Cahn–Hilliard Navier–Stokes set of equations. We discuss challenges and approaches to solving this coupled set of equations using a stabilized finite element formulation, especially in the case of a large density ratio between the two fluids. Specific features that enabled efficient solution of the equations include: (i) a conservative form of the convective term in the Cahn–Hilliard equation which ensures mass conservation of both fluid components; (ii) a continuous formula to compute the interfacial surface tension which results in lower requirement on the spatial resolution of the interface; and (iii) a four-step fractional scheme to decouple pressure from velocity in the Navier–Stokes equation. These are integrated with standard streamline-upwind Petrov–Galerkin stabilization to avoid spurious oscillations. We perform numerical tests to determine the minimal resolution of spatial discretization. Finally, we illustrate the accuracy of the framework using the analytical results of Prosperetti for a damped oscillating interface between two fluids with a density contrast.

  15. 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.

  16. Geriatric nutritional risk index as a prognostic factor in patients with diffuse large B cell lymphoma.

    Science.gov (United States)

    Kanemasa, Yusuke; Shimoyama, Tatsu; Sasaki, Yuki; Hishima, Tsunekazu; Omuro, Yasushi

    2018-06-01

    The geriatric nutritional risk index (GNRI) is a simple and well-established nutritional assessment tool that is a significant prognostic factor for various cancers. However, the role of the GNRI in predicting clinical outcomes of diffuse large B cell lymphoma (DLBCL) patients has not been investigated. To address this issue, we retrospectively analyzed a total of 476 patients with newly diagnosed de novo DLBCL. We defined the best cutoff value of the GNRI as 96.8 using a receiver operating characteristic curve. Patients with a GNRI risk by National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI), the 5-year OS was significantly lower in patients with a GNRI risk, 59.5 vs. 75.2%, P = 0.006; high risk, 37.4 vs. 64.9%, P = 0.033). In the present study, we demonstrated that the GNRI was an independent prognostic factor in DLBCL patients. The GNRI could identify a population of poor-risk patients among those with high-intermediate and high-risk by NCCN-IPI.

  17. Structural consequences of diffuse traumatic brain injury: A large deformation tensor-based morphometry study

    Science.gov (United States)

    Kim, Junghoon; Avants, Brian; Patel, Sunil; Whyte, John; Coslett, H. Branch; Pluta, John; Detre, John A.; Gee, James C.

    2008-01-01

    Traumatic brain injury (TBI) is one of the most common causes of long-term disability. Despite the importance of identifying neuropathology in individuals with chronic TBI, methodological challenges posed at the stage of inter-subject image registration have hampered previous voxel-based MRI studies from providing a clear pattern of structural atrophy after TBI. We used a novel symmetric diffeomorphic image normalization method to conduct a tensor-based morphometry (TBM) study of TBI. The key advantage of this method is that it simultaneously estimates an optimal template brain and topology preserving deformations between this template and individual subject brains. Detailed patterns of atrophies are then revealed by statistically contrasting control and subject deformations to the template space. Participants were 29 survivors of TBI and 20 control subjects who were matched in terms of age, gender, education, and ethnicity. Localized volume losses were found most prominently in white matter regions and the subcortical nuclei including the thalamus, the midbrain, the corpus callosum, the mid- and posterior cingulate cortices, and the caudate. Significant voxel-wise volume loss clusters were also detected in the cerebellum and the frontal/temporal neocortices. Volume enlargements were identified largely in ventricular regions. A similar pattern of results was observed in a subgroup analysis where we restricted our analysis to the 17 TBI participants who had no macroscopic focal lesions (total lesion volume> 1.5 cm 3). The current study confirms, extends, and partly challenges previous structural MRI studies in chronic TBI. By demonstrating that a large deformation image registration technique can be successfully combined with TBM to identify TBI-induced diffuse structural changes with greater precision, our approach is expected to increase the sensitivity of future studies examining brain-behavior relationships in the TBI population. PMID:17999940

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

    International Nuclear Information System (INIS)

    Kwanhian, Wiyada; Lenze, Dido; Alles, Julia; Motsch, Natalie; Barth, Stephanie; Döll, Celina; Imig, Jochen; Hummel, Michael; Tinguely, Marianne; Trivedi, Pankaj; Lulitanond, Viraphong; Meister, Gunter; Renner, Christoph; Grässer, Friedrich A

    2012-01-01

    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

  19. Discrimination method of large log-likelihood study in differential diagnosis of pulmonary diffuse mild micro-nodule

    International Nuclear Information System (INIS)

    Chen Budong; Ma Daqing; He Wen; Tang Hongqu; Qian Linxue; Zhou Ronglin

    2001-01-01

    Objective: To analyze HRCT and thin-slice CT scan findings in 150 patients with pulmonary diffuse mild micro-nodule, and to find the features with the purpose of identifying random micro-nodule, peri-lymphatic micro-nodule, and centrilobular micro-nodule. Methods: The useful features i 150 patients with pulmonary diffuse mild micro-nodule were translated into scores by means of discrimination method of large log-likelihood to identify the micro-nodular category. Results: The accuracy of diagnosis was 94.0% for random micro-nodule, 76.0% for peri-lymphatic micro-nodule, and 90.0% for centrilobular micro-nodule. Conclusion: HRCT and thin-slice CT scans were helpful in differential diagnosis of pulmonary diffuse mild micro-nodule. The discrimination method of large log-likelihood was propitious to diagnosis and differential diagnosis

  20. NASA/DOD Aerospace Knowledge Diffusion Research Project. Paper 59: Japanese Technological Innovation. Implications for Large Commercial Aircraft and Knowledge Diffusion

    Science.gov (United States)

    Pinelli, Thomas E.; Barclay, Rebecca O.; Kotler, Mindy L.

    1997-01-01

    This paper explores three factors-public policy, the Japanese (national) innovation system, and knowledge-that influence technological innovation in Japan. To establish a context for the paper, we examine Japanese culture and the U.S. and Japanese patent systems in the background section. A brief history of the Japanese aircraft industry as a source of knowledge and technology for other industries is presented. Japanese and U.S. alliances and linkages in three sectors-biotechnology, semiconductors, and large commercial aircraft (LCA)-and the importation, absorption, and diffusion of knowledge and technology are examined next. The paper closes with implications for diffusing knowledge and technology, U.S. public policy, and LCA.

  1. Aberrant methylation of cell-free circulating DNA in plasma predicts poor outcome in diffuse large B cell lymphoma

    DEFF Research Database (Denmark)

    Sommer Kristensen, Lasse; Hansen, Jakob Werner; Kristensen, Søren Sommer

    2016-01-01

    BACKGROUND: The prognostic value of aberrant DNA methylation of cell-free circulating DNA in plasma has not previously been evaluated in diffuse large B cell lymphoma (DLBCL). The aim of this study was to investigate if aberrant promoter DNA methylation can be detected in plasma from DLBCL patients...

  2. AKT Hyperactivation and the Potential of AKT-Targeted Therapy in Diffuse Large B-Cell Lymphoma

    DEFF Research Database (Denmark)

    Wang, Jinfen; Xu-Monette, Zijun Y; Jabbar, Kausar J

    2017-01-01

    AKT signaling is important for proliferation and survival of tumor cells. The clinical significance of AKT activation in diffuse large B-cell lymphoma (DLBCL) is not well analyzed. Here, we assessed expression of phosphorylated AKT (p-AKT) in 522 DLBCL patients. We found that high levels of p-AKT...

  3. Clinical and Biologic Significance of MYC Genetic Mutations in De Novo Diffuse Large B-cell Lymphoma

    NARCIS (Netherlands)

    Xu-Monette, Z.Y.; Deng, Q.; Manyam, G.C.; Tzankov, A.; Li, L; Xia, Y.; Wang, X.X.; Zou, D.; Visco, C.; Dybkaer, K.; Li, J.; Zhang, L.; Liang, H.; Montes-Moreno, S.; Chiu, A.; Orazi, A.; Zu, Y.; Bhagat, G.; Richards, K.L.; Hsi, E.D.; Choi, W.W.; Krieken, J.H.J.M. van; Huh, J.; Ponzoni, M.; Ferreri, A.J.; Parsons, B.M.; Moller, M.B.; Wang, S.A.; Miranda, R.N.; Piris, M.A.; Winter, J.N.; Medeiros, L.J.; Li, Y.; Young, K.H.

    2016-01-01

    PURPOSE: MYC is a critical driver oncogene in many cancers, and its deregulation in the forms of translocation and overexpression has been implicated in lymphomagenesis and progression of diffuse large B-cell lymphoma (DLBCL). The MYC mutational profile and its roles in DLBCL are unknown. This study

  4. Prognostic Relevance of Immunohistochemical Subclassification of Diffuse Large B-Cell Lymphoma in Two Prospective Phase III Clinical Trials

    NARCIS (Netherlands)

    Rayman, Nazik; Lam, King H.; van der Holt, Bronno; Koss, Clara; Veldhuizen, Dennis; Budel, Leo M.; Mulder, Andries H.; Verdonck, Leo F.; Delwel, Ruud; de Jong, Daphne; van Imhoff, Gustaaf W.; Sonneveld, Pieter

    Purpose: Until now molecular biologic techniques have not been easily used in daily clinical practice to stratify patients for therapeutic purposes. Therefore, we have investigated the prognostic relevance of the immunohistochemical (IHC) germinal center B-cell (GCB) versus non-GCB diffuse large

  5. Low GILT expression is associated with poor patient survival in diffuse large B-cell lymphoma

    Directory of Open Access Journals (Sweden)

    Hannah ePhipps-Yonas

    2013-12-01

    Full Text Available The MHC class II-restricted antigen processing pathway presents antigenic peptides acquired in the endocytic route for the activation of CD4+ T cells. Multiple cancers express MHC class II, which may influence the anti-tumor immune response and patient outcome. Low MHC class II expression is associated with poor survival in diffuse large B-cell lymphoma (DLBCL, the most common form of aggressive non-Hodgkin lymphoma. Therefore, we investigated whether gamma-interferon-inducible lysosomal thiol reductase (GILT, an upstream component of the MHC class II-restricted antigen processing pathway that is not regulated by the transcription factor class II transactivator, may be important in DLBCL biology. GILT reduces protein disulfide bonds in the endocytic compartment, exposing additional epitopes for MHC class II binding and facilitating antigen presentation. In each of four independent gene expression profiling cohorts with a total of 585 DLBCL patients, low GILT expression was significantly associated with poor overall survival. In contrast, low expression of a classical MHC class II gene, HLA-DRA, was associated with poor survival in one of four cohorts. The association of low GILT expression with poor survival was independent of established clinical and molecular prognostic factors, the International Prognostic Index and the cell of origin classification, respectively. Immunohistochemical analysis of GILT expression in 96 DLBCL cases demonstrated variation in GILT protein expression within tumor cells which correlated strongly with GILT mRNA expression. These studies identify a novel association between GILT expression and clinical outcome in lymphoma. Our findings underscore the role of antigen processing in DLBCL and suggest that molecules targeting this pathway warrant investigation as potential therapeutics.

  6. 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.

  7. 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.

  8. Subsequent primary malignancies after diffuse large B-cell lymphoma in the modern treatment era.

    Science.gov (United States)

    Tao, Li; Clarke, Christina A; Rosenberg, Aaron S; Advani, Ranjana H; Jonas, Brian A; Flowers, Christopher R; Keegan, Theresa H M

    2017-07-01

    With the addition of rituximab and other treatment advances, survival after diffuse large B-cell lymphoma (DLBCL) has improved, but subsequent primary malignancies (SPMs) have emerged as an important challenge for DLBCL survivorship. We calculated standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for SPMs among 23 879 patients who survived at least 1 year after a first primary DLBCL diagnosed during 1989-2012, compared to the general population in California. Cumulative incidence (CMI) of SPMs, accounting for the competing risk of death, also was calculated. We found that the incidence of acute myeloid leukaemia (AML) nearly doubled in the post-rituximab era [SIR (95% CI) 4·39 (2·51-7·13) pre- (1989-2000) and 8·70 (6·62-11·22) post-rituximab (2001-2012)]. Subsequent thyroid cancer was rare pre-rituximab, but increased substantially after 2001 [0·66 (0·08-2·37) vs. 2·27(1·44-3·41)]. The 5-year CMI for all SPMs (4·77% pre- vs. 5·41% post-rituximab, P = 0·047), AML (0·15% vs. 0·41%, P = 0·003), thyroid cancer (0·03% vs. 0·15%, P = 0·003) and melanoma (0·25% vs. 0·42%, P = 0·020) were greater in DLBCL patients diagnosed in the post- versus pre-rituximab period. This study provides insight into the changing pattern of SPM occurrence after the introduction of rituximab, which may elucidate the aetiology of SPMs and should guide future cancer surveillance efforts among DLBCL patients. © 2017 John Wiley & Sons Ltd.

  9. Large Time Asymptotics for a Continuous Coagulation-Fragmentation Model with Degenerate Size-Dependent Diffusion

    KAUST Repository

    Desvillettes, Laurent; Fellner, Klemens

    2010-01-01

    We study a continuous coagulation-fragmentation model with constant kernels for reacting polymers (see [M. Aizenman and T. Bak, Comm. Math. Phys., 65 (1979), pp. 203-230]). The polymers are set to diffuse within a smooth bounded one

  10. Diffusion of hydrogen, hydrogen sulfide and large molecular weight anions in bentonite

    International Nuclear Information System (INIS)

    Eriksen, T.E.; Jacobsson, A.

    1982-01-01

    The diffusivities of HS - and H 2 have been determined from profile analysis and steady state transport experiments. The diffusivity of HS - was found to be 9x10 - 12 and 4x10xsec 1 in MX-80 and Erbsloeh bentonite respectively. The results are in fair agreement with the results earlier obtained for Cl - and I - . The H 2 diffusivity calculated from steady state transport was found to be surprisingly low (3.6x10 - 12 m 2 xsec - 1 ). Various heavy anions with molecular weights 290-30x10 3 were found to migrate through MX-80 bentonite with diffusivities in the range (2,1-0,75)x10 - 15 m 2 xsec - 1 . (Author)

  11. Spectrum of the isotropic diffuse gamma-ray emission derived from first-year Fermi Large Area Telescope data.

    Science.gov (United States)

    Abdo, A A; Ackermann, M; Ajello, M; Atwood, W B; Baldini, L; Ballet, J; Barbiellini, G; Bastieri, D; Baughman, B M; Bechtol, K; Bellazzini, R; Berenji, B; Blandford, R D; Bloom, E D; Bonamente, E; Borgland, A W; Bregeon, J; Brez, A; Brigida, M; Bruel, P; Burnett, T H; Buson, S; Caliandro, G A; Cameron, R A; Caraveo, P A; Casandjian, J M; Cavazzuti, E; Cecchi, C; Celik, O; Charles, E; Chekhtman, A; Cheung, C C; Chiang, J; Ciprini, S; Claus, R; Cohen-Tanugi, J; Cominsky, L R; Conrad, J; Cutini, S; Dermer, C D; de Angelis, A; de Palma, F; Digel, S W; Di Bernardo, G; do Couto e Silva, E; Drell, P S; Drlica-Wagner, A; Dubois, R; Dumora, D; Farnier, C; Favuzzi, C; Fegan, S J; Focke, W B; Fortin, P; Frailis, M; Fukazawa, Y; Funk, S; Fusco, P; Gaggero, D; Gargano, F; Gasparrini, D; Gehrels, N; Germani, S; Giebels, B; Giglietto, N; Giommi, P; Giordano, F; Glanzman, T; Godfrey, G; Grenier, I A; Grondin, M-H; Grove, J E; Guillemot, L; Guiriec, S; Gustafsson, M; Hanabata, Y; Harding, A K; Hayashida, M; Hughes, R E; Itoh, R; Jackson, M S; Jóhannesson, G; Johnson, A S; Johnson, R P; Johnson, T J; Johnson, W N; Kamae, T; Katagiri, H; Kataoka, J; Kawai, N; Kerr, M; Knödlseder, J; Kocian, M L; Kuehn, F; Kuss, M; Lande, J; Latronico, L; Lemoine-Goumard, M; Longo, F; Loparco, F; Lott, B; Lovellette, M N; Lubrano, P; Madejski, G M; Makeev, A; Mazziotta, M N; McConville, W; McEnery, J E; Meurer, C; Michelson, P F; Mitthumsiri, W; Mizuno, T; Moiseev, A A; Monte, C; Monzani, M E; Morselli, A; Moskalenko, I V; Murgia, S; Nolan, P L; Norris, J P; Nuss, E; Ohsugi, T; Omodei, N; Orlando, E; Ormes, J F; Paneque, D; Panetta, J H; Parent, D; Pelassa, V; Pepe, M; Pesce-Rollins, M; Piron, F; Porter, T A; Rainò, S; Rando, R; Razzano, M; Reimer, A; Reimer, O; Reposeur, T; Ritz, S; Rochester, L S; Rodriguez, A Y; Roth, M; Ryde, F; Sadrozinski, H F-W; Sanchez, D; Sander, A; Saz Parkinson, P M; Scargle, J D; Sellerholm, A; Sgrò, C; Shaw, M S; Siskind, E J; Smith, D A; Smith, P D; Spandre, G; Spinelli, P; Starck, J-L; Strickman, M S; Strong, A W; Suson, D J; Tajima, H; Takahashi, H; Takahashi, T; Tanaka, T; Thayer, J B; Thayer, J G; Thompson, D J; Tibaldo, L; Torres, D F; Tosti, G; Tramacere, A; Uchiyama, Y; Usher, T L; Vasileiou, V; Vilchez, N; Vitale, V; Waite, A P; Wang, P; Winer, B L; Wood, K S; Ylinen, T; Ziegler, M

    2010-03-12

    We report on the first Fermi Large Area Telescope (LAT) measurements of the so-called "extragalactic" diffuse gamma-ray emission (EGB). This component of the diffuse gamma-ray emission is generally considered to have an isotropic or nearly isotropic distribution on the sky with diverse contributions discussed in the literature. The derivation of the EGB is based on detailed modeling of the bright foreground diffuse Galactic gamma-ray emission, the detected LAT sources, and the solar gamma-ray emission. We find the spectrum of the EGB is consistent with a power law with a differential spectral index gamma = 2.41 +/- 0.05 and intensity I(>100 MeV) = (1.03 +/- 0.17) x 10(-5) cm(-2) s(-1) sr(-1), where the error is systematics dominated. Our EGB spectrum is featureless, less intense, and softer than that derived from EGRET data.

  12. Benefit of Consolidative Radiation Therapy for Primary Bone Diffuse Large B-Cell Lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Tao, Randa; Allen, Pamela K. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Rodriguez, Alma [Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Shihadeh, Ferial; Pinnix, Chelsea C.; Arzu, Isadora; Reed, Valerie K. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Oki, Yasuhiro; Westin, Jason R.; Fayad, Luis E.; Medeiros, L. Jeffrey [Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Dabaja, Bouthaina, E-mail: bdabaja@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2015-05-01

    Purpose: Outcomes for patients with diffuse large B-cell lymphoma (DLBCL) differ according to the site of presentation. With effective chemotherapy, the need for consolidative radiation therapy (RT) is controversial. We investigated the influence of primary bone presentation and receipt of consolidative RT on progression-free survival (PFS) and overall survival (OS) in patients with DLBCL. Methods and Materials: We identified 102 patients with primary bone DLBCL treated consecutively from 1988 through 2013 and extracted clinical, pathologic, and treatment characteristics from the medical records. Survival outcomes were calculated by the Kaplan-Meier method, with factors affecting survival determined by log-rank tests. Univariate and multivariate analyses were done with a Cox regression model. Results: The median age was 55 years (range, 16-87 years). The most common site of presentation was in the long bones. Sixty-five patients (63%) received R-CHOP–based chemotherapy, and 74 (72%) received rituximab. RT was given to 67 patients (66%), 47 with stage I to II and 20 with stage III to IV disease. The median RT dose was 44 Gy (range, 24.5-50 Gy). At a median follow-up time of 82 months, the 5-year PFS and OS rates were 80% and 82%, respectively. Receipt of RT was associated with improved 5-year PFS (88% RT vs 63% no RT, P=.0069) and OS (91% vs 68%, P=.0064). On multivariate analysis, the addition of RT significantly improved PFS (hazard ratio [HR] = 0.14, P=.014) with a trend toward an OS benefit (HR=0.30, P=.053). No significant difference in PFS or OS was found between patients treated with 30 to 35 Gy versus ≥36 Gy (P=.71 PFS and P=.31 OS). Conclusion: Patients with primary bone lymphoma treated with standard chemotherapy followed by RT can have excellent outcomes. The use of consolidative RT was associated with significant benefits in both PFS and OS.

  13. Benefit of Consolidative Radiation Therapy for Primary Bone Diffuse Large B-Cell Lymphoma

    International Nuclear Information System (INIS)

    Tao, Randa; Allen, Pamela K.; Rodriguez, Alma; Shihadeh, Ferial; Pinnix, Chelsea C.; Arzu, Isadora; Reed, Valerie K.; Oki, Yasuhiro; Westin, Jason R.; Fayad, Luis E.; Medeiros, L. Jeffrey; Dabaja, Bouthaina

    2015-01-01

    Purpose: Outcomes for patients with diffuse large B-cell lymphoma (DLBCL) differ according to the site of presentation. With effective chemotherapy, the need for consolidative radiation therapy (RT) is controversial. We investigated the influence of primary bone presentation and receipt of consolidative RT on progression-free survival (PFS) and overall survival (OS) in patients with DLBCL. Methods and Materials: We identified 102 patients with primary bone DLBCL treated consecutively from 1988 through 2013 and extracted clinical, pathologic, and treatment characteristics from the medical records. Survival outcomes were calculated by the Kaplan-Meier method, with factors affecting survival determined by log-rank tests. Univariate and multivariate analyses were done with a Cox regression model. Results: The median age was 55 years (range, 16-87 years). The most common site of presentation was in the long bones. Sixty-five patients (63%) received R-CHOP–based chemotherapy, and 74 (72%) received rituximab. RT was given to 67 patients (66%), 47 with stage I to II and 20 with stage III to IV disease. The median RT dose was 44 Gy (range, 24.5-50 Gy). At a median follow-up time of 82 months, the 5-year PFS and OS rates were 80% and 82%, respectively. Receipt of RT was associated with improved 5-year PFS (88% RT vs 63% no RT, P=.0069) and OS (91% vs 68%, P=.0064). On multivariate analysis, the addition of RT significantly improved PFS (hazard ratio [HR] = 0.14, P=.014) with a trend toward an OS benefit (HR=0.30, P=.053). No significant difference in PFS or OS was found between patients treated with 30 to 35 Gy versus ≥36 Gy (P=.71 PFS and P=.31 OS). Conclusion: Patients with primary bone lymphoma treated with standard chemotherapy followed by RT can have excellent outcomes. The use of consolidative RT was associated with significant benefits in both PFS and OS

  14. De Novo Nodal Diffuse Large B-Cell Lymphoma: Identification of Biologic Prognostic Factors

    International Nuclear Information System (INIS)

    Abd El-Hameed, A.

    2005-01-01

    Diffuse large B-cell Lymphoma (DLBCL) represents the most frequent type of non-Hodgkin lymphoma (NHL). Although combination chemotherapy has improved the outcome, long-term cure is now possible for approximately 50% of all patients. making the search for parameters identifying patients at high risk particularly needed. The presence of bcl-2 gene rearrangement in de novo DLBCL suggests a possible follicle center cell origin and perhaps a distinct clinical behavior. This study investigated the frequency and prognostic significance of t( 14; 18) translocation and bcl-2 protein overexpression in a cohort of patients with de novo nodal DLBCL who where uniformly evaluated and treated. Material and Methods: A total of 40 patients with de novo nodal DLBCL treated at National Cancer Institute (NCI), Cairo University were investigated. Formal infixed, paraffin-embedded sections were analyzed for: I) bcl-2 gene rearrangement including major break point region (mbr) and minor cluster region (mcr) by polymerase chain reaction (PCR). and 2) bcl-2 protein expression by immunohistochemistry using Dako 124 clone. Results were correlated with the clinical features and subsequent clinical course. Bcl-2 gene rearrangement was detected in 8 cases (20%). 2 cases at mbr, and 6 cases at mcr. Bcl-2 protein (> I 0%) was expressed in 24 cases (60%), irrespective of the presence of t( 14; 18) translocation. The t( 14; 18), and bcl-2 protein overexpression were more frequently associated with failure to achieve a complete response to therapy (ρ=0.008. and 0.04. respectively). DLBCL patients with t(14;18), and bcl-2 protein expression had a significantly reduced 5-year disease free survival (ρ=0.04, and 0.01, respectively). The t( 14; 18) translocation, and bcl-2 protein expression define a group of DLBCL patients with a poor prognosis, and could be used to tailor treatment, and to identify candidates for therapeutic approaches. Geographic differences in t(14;18) may be related to the

  15. Large size self-assembled quantum rings: quantum size effect and modulation on the surface diffusion.

    Science.gov (United States)

    Tong, Cunzhu; Yoon, Soon Fatt; Wang, Lijun

    2012-09-24

    We demonstrate experimentally the submicron size self-assembled (SA) GaAs quantum rings (QRs) by quantum size effect (QSE). An ultrathin In0.1 Ga0.9As layer with different thickness is deposited on the GaAs to modulate the surface nucleus diffusion barrier, and then the SA QRs are grown. It is found that the density of QRs is affected significantly by the thickness of inserted In0.1 Ga0.9As, and the diffusion barrier modulation reflects mainly on the first five monolayer . The physical mechanism behind is discussed. The further analysis shows that about 160 meV decrease in diffusion barrier can be achieved, which allows the SA QRs with density of as low as one QR per 6 μm2. Finally, the QRs with diameters of 438 nm and outer diameters of 736 nm are fabricated using QSE.

  16. Discovery of small-scale-structure in the large molecule/dust distribution in the diffuse ISM

    Science.gov (United States)

    Cordiner, Martin A.; Fossey, Stephen J.; Sarre, Peter J.

    There is mounting evidence that far from being homogeneously distributed, interstellar matter can have a clumpy or filamentary structure on the scale of 10s to a few 1000s of AU and which is commonly described as small scale structure (SSS). Initially confined to VLBI HI observations and HI observations of high-velocity pulsars, evidence for SSS has also come indirectly from molecular radio studies of e.g. HCO+ and infrared absorption by H3+. Much of the recent data on SSS has been obtained through optical/UV detection of atomic and diatomic molecular lines. Is there small scale structure in the large molecule/dust distribution? While this question could in principle be explored by measuring differences in the interstellar extinction towards the components of binary stars, in practice this would be difficult. Rather we chose to investigate this by recording very high signal-to-noise spectra of diffuse interstellar absorption bands. Although the carriers remain unidentified, the diffuse bands are generally considered to be tracers of the large molecule/dust distribution and scale well with reddening. Using the Anglo-Australian Telescope we have made UCLES observations of pairs of stars with separations ranging between 500 and 30000 AU. The signal-to-noise achieved was up to 2000, thus allowing variations in central depth of less than a few tenths of a percent to be discernible. Striking differences in diffuse band strengths for closely spaced lines of sight are found showing clearly that there exists small-scale-structure in the large molecule/dust distribution. For example, in the Ophiuchus star-formation region the central depths for the λ6614 diffuse band towards the ρ Oph stars A, B, C and D/E all differ and range between 0.966 and 0.930. Further interesting behaviour is found when comparing the relative strengths of diffuse bands between closely parallel lines of sight. Taking again the ρ Oph group, for λ5797 the strengths follow the order DE > B > C > A

  17. Spontaneous regression of primary cutaneous diffuse large B-cell lymphoma, leg type with significant T-cell immune response

    Directory of Open Access Journals (Sweden)

    Paul M. Graham, DO

    2018-05-01

    Full Text Available We report a case of histologically confirmed primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT that subsequently underwent spontaneous regression in the absence of systemic treatment. The case showed an atypical lymphoid infiltrate that was CD20+ and MUM-1+ and CD10–. A subsequent biopsy of the spontaneously regressed lesion showed fibrosis associated with a lymphocytic infiltrate comprising reactive T cells. PCDLBCL-LT is a cutaneous B-cell lymphoma with a poor prognosis, which is usually treated with chemotherapy. We describe a case of clinical and histologic spontaneous regression in a patient with PCDLBCL-LT who had a negative systemic workup but a recurrence over a year after his initial presentation. Key words: B cell, lymphoma, primary cutaneous diffuse large B-cell lymphoma, leg type, regression

  18. Transformation of a Cutaneous Follicle Center Lymphoma to a Diffuse Large B-Cell Lymphoma—An Unusual Presentation

    Directory of Open Access Journals (Sweden)

    J. Dias Coelho

    2010-01-01

    Full Text Available Primary cutaneous follicle center lymphoma (PCFCL is characterized by a proliferation of follicle center cells in the skin. A definitive diagnosis is frequently delayed because of difficulties in interpretation of the histopathologic findings. It has an excellent prognosis with a 5-year survival over 95% and its risk of transformation has not been established. We describe a case report of man with a gastric diffuse large B-cell lymphoma (DLBCL referred to our clinic because of nodules in the back that had gradually developed over a period of 10 years. A biopsy performed 3 years before was interpreted as reactive follicular hyperplasia. A new skin biopsy revealed a diffuse large B-cell lymphoma and immunoglobulin heavy chain gene rearrangements from the initial skin biopsy (PCBCL and the DLBCL gastric biopsy were studied by polymerase chain reaction and an identical clonal rearrangement was detected which was highly suggestive of a transformation lymphoma.

  19. Rearrangements of MYC gene facilitate risk stratification in diffuse large B-cell lymphoma patients treated with rituximab-CHOP

    DEFF Research Database (Denmark)

    Tzankov, Alexandar; Xu-Monette, Zijun Y; Gerhard, Marc

    2014-01-01

    In order to address the debatable prognostic role of MYC rearrangements in diffuse large B-cell lymphoma patients treated with rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone, we evaluated MYC rearrangements by fluorescence in situ hybridization in 563 cases using...... with the dual-fusion probes, 15 detectable only with the break-apart probes and 20 detectable with both dual-fusion probes and break-apart probes. MYC rearrangements correlated with germinal center B-cell origin (P=0.02), MYC protein expression (P=0.032), and larger tumor mass size (P=0.0003). Patients with MYC...... was prognostically additive. Radiotherapy seemed to diminish the prognostic effects of MYC rearrangements in diffuse large B-cell lymphoma patients since only 2/10 irradiated patients with MYC rearrangements died of/with disease, compared with 16/28 non-irradiated patients with MYC rearrangements. We conclude...

  20. Glutathione peroxidase 4 overexpression inhibits ROS-induced cell death in diffuse large B-cell lymphoma.

    Science.gov (United States)

    Kinowaki, Yuko; Kurata, Morito; Ishibashi, Sachiko; Ikeda, Masumi; Tatsuzawa, Anna; Yamamoto, Masahide; Miura, Osamu; Kitagawa, Masanobu; Yamamoto, Kouhei

    2018-02-20

    Regulation of oxidative stress and redox systems has important roles in carcinogenesis and cancer progression, and for this reason has attracted much attention as a new area of cancer therapeutic targets. Glutathione peroxidase 4 (GPX4), an antioxidant enzyme, has biological important functions such as signaling cell death by suppressing peroxidation of membrane phospholipids. However, few studies exist on the expression and clinical relevance of GPX4 in malignant lymphomas such as diffuse large B-cell lymphoma. In this study, we assessed the expression of GPX4 immunohistochemically. GPX4 was expressed in 35.5% (33/93) cases of diffuse large B-cell lymphoma. The GPX4-positive group had poor overall survival (P = 0.0032) and progression-free survival (P = 0.0004) compared with those of the GPX4-negative group. In a combined analysis of GPX4 and 8-hydroxydeoxyguanosine (8-OHdG), an oxidative stress marker, there was a negative correlation between GPX4 and 8-hydroxydeoxyguanosine (P = 0.0009). The GPX4-positive and 8-hydroxydeoxyguanosine-negative groups had a significantly worse prognosis than the other groups in both overall survival (P = 0.0170) and progression-free survival (P = 0.0005). These results suggest that the overexpression of GPX4 is an independent prognostic predictor in diffuse large B-cell lymphoma. Furthermore, in vitro analysis demonstrated that GPX4-overexpressing cells were resistant to reactive oxygen species-induced cell death (P = 0.0360). Conversely, GPX4-knockdown cells were sensitive to reactive oxygen species-induced cell death (P = 0.0111). From these data, we conclude that GPX4 regulates reactive oxygen species-induced cell death. Our results suggest a novel therapeutic strategy using the mechanism of ferroptosis, as well as a novel prognostic predictor of diffuse large B-cell lymphoma.

  1. Multifocal Gastric Ulcers Caused by Diffuse Large B Cell Lymphoma in a Patient With Significant Weight Loss

    OpenAIRE

    Gromski, Mark A.; Peng, Jennifer L.; Zhou, Jiehao; Masuoka, Howard C.; Suvannasankha, Attaya; Liangpunsakul, Suthat

    2016-01-01

    Primary gastrointestinal (GI) lymphoma is a heterogeneous disease with varied clinical presentations. The stomach is the most common GI site and accounts for 70% to 75% of GI lymphomas. We present a patient with gastric diffuse large B cell lymphoma (DLBCL) who presented with significant weight loss, early satiety, and multifocal ulcerated gastric lesions. Esophagoduodenoscopy should be performed in patients presenting with warning symptoms as in our case. Diagnosis is usually made by endosco...

  2. Relapsed Diffuse Large B-Cell Lymphoma Treated by Reduced-Intensity Allogeneic Stem Cell Transplantation with Donor Lymphocyte Infusion

    International Nuclear Information System (INIS)

    Chudhry, Q.N.; Ahmed, P.; Ullah, K.; Satti, T.M.; Raza, S.; Mehmood, S.K.; Akram, M.; Ahmed, S.

    2010-01-01

    A 42 years old male with relapsed diffuse large B-cell lymphoma was given second-line chemotherapy followed by reduced intensity allogeneic stem cell transplantation from HLA matched brother. Twelve weeks post transplant, his disease relapsed evidenced by the appearance of lymphoma cells in the peripheral blood and declining donor chimerism. Donor lymphocyte infusion was given that induced complete lymphoma remission. The patient is well 3 years post transplant with his disease in complete remission. (author)

  3. A rare case of anasarca caused by infiltration of the pituitary gland by diffuse large B-cell lymphoma

    OpenAIRE

    Kumabe, Ayako; Kenzaka, Tsuneaki; Nishimura, Yoshioki; Aikawa, Masaki; Mori, Masaki; Matsumura, Masami

    2015-01-01

    Background Anasarca in patients with lymphoma is a rare symptom. We report a patient with DLBCL associated with pituitary gland infiltration that was diagnosed based on significant anasarca. Case presentation A 72-year-old woman with a 10-year history of hypertension visited a local hospital presenting with anasarca and 15-kg weight gain in the past 3?months. we clinically diagnosed central hypothyroidism caused by pituitary gland infiltration of diffuse large B-cell lymphoma (DLBCL) (clinica...

  4. Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing

    OpenAIRE

    Lohr, Jens G.; Stojanov, Petar; Lawrence, Michael S.; Auclair, Daniel; Chapuy, Bjoern; Sougnez, Carrie; Cruz-Gordillo, Peter; Knoechel, Birgit; Asmann, Yan W.; Slager, Susan L.; Novak, Anne J.; Dogan, Ahmet; Ansell, Stephen M.; Link, Brian K.; Zou, Lihua

    2012-01-01

    To gain insight into the genomic basis of diffuse large B-cell lymphoma (DLBCL), we performed massively parallel whole-exome sequencing of 55 primary tumor samples from patients with DLBCL and matched normal tissue. We identified recurrent mutations in genes that are well known to be functionally relevant in DLBCL, including MYD88, CARD11, EZH2, and CREBBP. We also identified somatic mutations in genes for which a functional role in DLBCL has not been previously suspected. These genes include...

  5. Adsorption and diffusion of Ru adatoms on Ru(0001)-supported graphene: Large-scale first-principles calculations

    Energy Technology Data Exchange (ETDEWEB)

    Han, Yong; Evans, James W. [Department of Physics and Astronomy, Iowa State University, Ames, Iowa 50011, USA and Ames Laboratory—U.S. Department of Energy, Iowa State University, Ames, Iowa 50011 (United States)

    2015-10-28

    Large-scale first-principles density functional theory calculations are performed to investigate the adsorption and diffusion of Ru adatoms on monolayer graphene (G) supported on Ru(0001). The G sheet exhibits a periodic moiré-cell superstructure due to lattice mismatch. Within a moiré cell, there are three distinct regions: fcc, hcp, and mound, in which the C{sub 6}-ring center is above a fcc site, a hcp site, and a surface Ru atom of Ru(0001), respectively. The adsorption energy of a Ru adatom is evaluated at specific sites in these distinct regions. We find the strongest binding at an adsorption site above a C atom in the fcc region, next strongest in the hcp region, then the fcc-hcp boundary (ridge) between these regions, and the weakest binding in the mound region. Behavior is similar to that observed from small-unit-cell calculations of Habenicht et al. [Top. Catal. 57, 69 (2014)], which differ from previous large-scale calculations. We determine the minimum-energy path for local diffusion near the center of the fcc region and obtain a local diffusion barrier of ∼0.48 eV. We also estimate a significantly lower local diffusion barrier in the ridge region. These barriers and information on the adsorption energy variation facilitate development of a realistic model for the global potential energy surface for Ru adatoms. This in turn enables simulation studies elucidating diffusion-mediated directed-assembly of Ru nanoclusters during deposition of Ru on G/Ru(0001)

  6. mTOR activity in AIDS-related diffuse large B-cell lymphoma.

    Directory of Open Access Journals (Sweden)

    Sara H Browne

    Full Text Available Patients infected with HIV have a significantly increased risk of developing non-Hodgkin lymphomas despite the widespread use of HAART. To investigate mTOR pathway activity in acquired immunodeficiency syndrome (AIDS related diffuse large B-cell lymphoma AR-DLBCL, we used immunohistochemistry to examine the presence of the phosphorylated 70 ribosomal S6 protein-kinase (p70S6K, an extensively studied effector of mTOR Complex 1 (mTORC1 and the phosphorylated phosphatase and tensin homolog (pPTEN, a negative regulator of mTORC1 pathway.We evaluated tissue samples from 126 patients with AR-DLBCL. Among them, 98 samples were from tissue microarrays (TMAs supplied by the Aids and Cancer Specimen Resource (ACSR, the remaining 28 samples were from cases diagnosed and treated at the University of California, San Diego (UCSD. The presence of p70S6K was evaluated with two antibodies directed against the combined epitopes Ser235/236 and Ser240/244, respectively; and additional monoclonal anti-bodies were used to identify pPTEN and phosphorylated proline-rich Akt substrate of 40kDa (pPRAS40. The degree of intensity and percentage of cells positive for p70S6K and pPTEN were assessed in all the samples. In addition, a subgroup of 28 patients from UCSD was studied to assess the presence of pPRAS40, an insulin-regulated activator of the mTORC1. The expression of each of these markers was correlated with clinical and histopathologic features.The majority of the patients evaluated were males (88%; only two cases (1.6% were older than 65 years of age. We found high levels of both p70S6K-paired epitopes studied, 48% positivity against Ser235/236 (44% in ACSR and 64% in UCSD group, and 86% positivity against Ser240/244 (82% in ACSR and 100% in UCSD group. We observed more positive cells and stronger intensity with epitope Ser240/244 in comparison to Ser235/236 (p<0.0001. The degree of intensity and percentage of cells positive for pPTEN was positively correlated with

  7. The ESO Diffuse Interstellar Bands Large Exploration Survey (EDIBLES) . I. Project description, survey sample, and quality assessment

    Science.gov (United States)

    Cox, Nick L. J.; Cami, Jan; Farhang, Amin; Smoker, Jonathan; Monreal-Ibero, Ana; Lallement, Rosine; Sarre, Peter J.; Marshall, Charlotte C. M.; Smith, Keith T.; Evans, Christopher J.; Royer, Pierre; Linnartz, Harold; Cordiner, Martin A.; Joblin, Christine; van Loon, Jacco Th.; Foing, Bernard H.; Bhatt, Neil H.; Bron, Emeric; Elyajouri, Meriem; de Koter, Alex; Ehrenfreund, Pascale; Javadi, Atefeh; Kaper, Lex; Khosroshadi, Habib G.; Laverick, Mike; Le Petit, Franck; Mulas, Giacomo; Roueff, Evelyne; Salama, Farid; Spaans, Marco

    2017-10-01

    The carriers of the diffuse interstellar bands (DIBs) are largely unidentified molecules ubiquitously present in the interstellar medium (ISM). After decades of study, two strong and possibly three weak near-infrared DIBs have recently been attributed to the C60^+ fullerene based on observational and laboratory measurements. There is great promise for the identification of the over 400 other known DIBs, as this result could provide chemical hints towards other possible carriers. In an effort tosystematically study the properties of the DIB carriers, we have initiated a new large-scale observational survey: the ESO Diffuse Interstellar Bands Large Exploration Survey (EDIBLES). The main objective is to build on and extend existing DIB surveys to make a major step forward in characterising the physical and chemical conditions for a statistically significant sample of interstellar lines-of-sight, with the goal to reverse-engineer key molecular properties of the DIB carriers. EDIBLES is a filler Large Programme using the Ultraviolet and Visual Echelle Spectrograph at the Very Large Telescope at Paranal, Chile. It is designed to provide an observationally unbiased view of the presence and behaviour of the DIBs towards early-spectral-type stars whose lines-of-sight probe the diffuse-to-translucent ISM. Such a complete dataset will provide a deep census of the atomic and molecular content, physical conditions, chemical abundances and elemental depletion levels for each sightline. Achieving these goals requires a homogeneous set of high-quality data in terms of resolution (R 70 000-100 000), sensitivity (S/N up to 1000 per resolution element), and spectral coverage (305-1042 nm), as well as a large sample size (100+ sightlines). In this first paper the goals, objectives and methodology of the EDIBLES programme are described and an initial assessment of the data is provided.

  8. Pembrolizumab and Vorinostat in Treating Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma, Follicular Lymphoma, or Hodgkin Lymphoma

    Science.gov (United States)

    2018-04-23

    Grade 3a Follicular Lymphoma; Grade 3b Follicular Lymphoma; Recurrent Classical Hodgkin Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Refractory Classical Hodgkin Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Mediastinal (Thymic) Large B-Cell Cell Lymphoma

  9. Primary diffuse large B-cell lymphoma of the corpora cavernosa presented as a perineal mass

    Directory of Open Access Journals (Sweden)

    González-Satué Carlos

    2012-01-01

    Full Text Available Primary male genital lymphomas may appear rarely in testis, and exceptionally in the penis and prostate, but there is not previous evidence of a lymphoma arising from the corpora cavernosa. We report the first case in the literature of a primary diffuse cell B lymphoma of the corpora cavernosa presented with low urinary tract symptoms, perineal pain and palpable mass. Diagnosis was based on trucut biopsy, histopathological studies and computed tomographic images.

  10. destiny: diffusion maps for large-scale single-cell data in R.

    Science.gov (United States)

    Angerer, Philipp; Haghverdi, Laleh; Büttner, Maren; Theis, Fabian J; Marr, Carsten; Buettner, Florian

    2016-04-15

    : Diffusion maps are a spectral method for non-linear dimension reduction and have recently been adapted for the visualization of single-cell expression data. Here we present destiny, an efficient R implementation of the diffusion map algorithm. Our package includes a single-cell specific noise model allowing for missing and censored values. In contrast to previous implementations, we further present an efficient nearest-neighbour approximation that allows for the processing of hundreds of thousands of cells and a functionality for projecting new data on existing diffusion maps. We exemplarily apply destiny to a recent time-resolved mass cytometry dataset of cellular reprogramming. destiny is an open-source R/Bioconductor package "bioconductor.org/packages/destiny" also available at www.helmholtz-muenchen.de/icb/destiny A detailed vignette describing functions and workflows is provided with the package. carsten.marr@helmholtz-muenchen.de or f.buettner@helmholtz-muenchen.de Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  11. From gas dynamics with large friction to gradient flows describing diffusion theories

    KAUST Repository

    Lattanzio, Corrado

    2016-12-09

    We study the emergence of gradient flows in Wasserstein distance as high friction limits of an abstract Euler flow generated by an energy functional. We develop a relative energy calculation that connects the Euler flow to the gradient flow in the diffusive limit regime. We apply this approach to prove convergence from the Euler-Poisson system with friction to the Keller-Segel system in the regime that the latter has smooth solutions. The same methodology is used to establish convergence from the Euler-Korteweg theory with monotone pressure laws to the Cahn-Hilliard equation.

  12. From gas dynamics with large friction to gradient flows describing diffusion theories

    KAUST Repository

    Lattanzio, Corrado; Tzavaras, Athanasios

    2016-01-01

    We study the emergence of gradient flows in Wasserstein distance as high friction limits of an abstract Euler flow generated by an energy functional. We develop a relative energy calculation that connects the Euler flow to the gradient flow in the diffusive limit regime. We apply this approach to prove convergence from the Euler-Poisson system with friction to the Keller-Segel system in the regime that the latter has smooth solutions. The same methodology is used to establish convergence from the Euler-Korteweg theory with monotone pressure laws to the Cahn-Hilliard equation.

  13. Prospective study of bone metastasis from prostate cancer: comparison between large field diffusion-weighted imaging and bone scintigraphy

    International Nuclear Information System (INIS)

    Wang Xiaoying; Zhang Chunyan; Jiang Xuexiang

    2009-01-01

    Objective: To evaluate the large field diffusion weighted imaging (DWI) (from head vertex to lower leg) in detection of bone metastases from prostate cancer. Methods: One hundred and sixty- six consecutive patients who were suspected of prostate cancer received pelvic MRI and large field diffusion weighted imaging examination. Forty-nine of them underwent bone scintigraphy within one month of the examination of large field DWI. The images were double-blindly evaluated without the knowledge of the pathology result. Conventional MR T 1 and fat saturation T 2 weighted images were taken as standard for the diagnosis of bone metastasis. The sensitivity, specificity, and area under curve between large field DWI and bone scintigraphy were compared with McNemar test. Five patients with bone metastases exceeding 10 per patient were excluded in the lesion-by-lesion analysis. Results: Ten of the 49 patients were diagnosed as bone metastases. The diagnosis of bone metastasis were made in 15 patients by large field DWI and in 17 patients by bone scintigraphy. With patient number as study units (n=49), the diagnostic sensitivity of bone metastases with large field DWI and bone metastases were both 100% (10/10), and specificity were 87.2% (34/39) vs. 82.1% (32/39), respectively. ROC study showed the area under curve (AUC) of large field DWI and bone scintigraphy were 0.936 vs. 0.910, respectively. Totally 68 abnormal foci were identified from large field DWI and/or bone scintigraphy in 44 patients (while 5 patients with bone metastases exceeding 10 foci per patient were excluded), 20 of them were diagnosed as foci of bone metastasis. The diagnosis of bone metastases was made in 23 foci by large field DWI and in 34 by bone scintigraphy. With lesion numbers as study units (n=68), the diagnostic sensitivity of large field DWI and bone scintigraphy were both 90.0% (18/20), and specificity were 89.6% (43/48) vs. 66.7% (32/48), respectively. ROC study showed the area under curve of

  14. Patterns of failure of diffuse large B-cell lymphoma patients after involved-site radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Holzhaeuser, Eva; Berlin, Maximilian; Bezold, Thomas; Mayer, Arnulf; Schmidberger, Heinz [University Medical Center Mainz, Department of Radiation Oncology and Radiotherapy, Mainz (Germany); Wollschlaeger, Daniel [University Medical Center Mainz, Institute for Medical Biostatistics, Epidemiology and Informatics, Mainz (Germany); Hess, Georg [University Medical Center Mainz, Department of Internal Medicine, Mainz (Germany)

    2017-12-15

    Radiotherapy (RT) in combination with chemoimmunotherapy is highly efficient in the treatment of diffuse large B-cell lymphoma (DLBCL). This retrospective analysis evaluated the efficacy of the treatment volume and the dose concept of involved-site RT (ISRT). We identified 60 histologically confirmed stage I-IV DLBCL patients treated with multimodal cytotoxic chemoimmunotherapy and followed by consolidative ISRT from 2005-2015. Progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier method. Univariate analyses were performed by log-rank test and Mann-Whitney U-test. After initial chemoimmunotherapy (mostly R-CHOP; rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone), 19 (36%) patients achieved complete response (CR), 34 (64%) partial response (PR) or less. Excluded were 7 (12%) patients with progressive disease after chemoimmunotherapy. All patients underwent ISRT with a dose of 40 Gy. After a median follow-up of 44 months, 79% of the patients remained disease free, while 21% presented with failure, progressive systemic disease, or death. All patients who achieved CR after chemoimmunotherapy remained in CR. Of the patients achieving PR after chemotherapy only 2 failed at the initial site within the ISRT volume. No marginal relapse was observed. Ann Arbor clinical stage I/II showed significantly improved PFS compared to stage III/IV (93% vs 65%; p ≤ 0.021). International Prognostic Index (IPI) score of 0 or 1 compared to 2-5 has been associated with significantly increased PFS (100% vs 70%; p ≤ 0.031). Postchemoimmunotherapy status of CR compared to PR was associated with significantly increased PFS (100% vs 68%; p ≤ 0.004) and OS (100% vs 82%; p ≤ 0.026). Only 3 of 53 patients developed grade II late side effects, whereas grade III or IV side effects have not been observed. These data suggest that a reduction of the RT treatment volume from involved-field (IF) to involved-site (IS) is sufficient because

  15. A thermodynamically consistent model of magneto-elastic materials under diffusion at large strains and its analysis

    Science.gov (United States)

    Roubíček, Tomáš; Tomassetti, Giuseppe

    2018-06-01

    A theory of elastic magnets is formulated under possible diffusion and heat flow governed by Fick's and Fourier's laws in the deformed (Eulerian) configuration, respectively. The concepts of nonlocal nonsimple materials and viscous Cahn-Hilliard equations are used. The formulation of the problem uses Lagrangian (reference) configuration while the transport processes are pulled back. Except the static problem, the demagnetizing energy is ignored and only local non-self-penetration is considered. The analysis as far as existence of weak solutions of the (thermo) dynamical problem is performed by a careful regularization and approximation by a Galerkin method, suggesting also a numerical strategy. Either ignoring or combining particular aspects, the model has numerous applications as ferro-to-paramagnetic transformation in elastic ferromagnets, diffusion of solvents in polymers possibly accompanied by magnetic effects (magnetic gels), or metal-hydride phase transformation in some intermetallics under diffusion of hydrogen accompanied possibly by magnetic effects (and in particular ferro-to-antiferromagnetic phase transformation), all in the full thermodynamical context under large strains.

  16. Gastric diffuse large B cell lymphoma presenting as para neoplastic cerebellar degeneration: Case report and review of literature

    International Nuclear Information System (INIS)

    Lakshmaiah, K.C.; Viveka, B.K.; Kumar, N.A.; Saini, M.L.; Sinha, S.; Saini, K.S.

    2013-01-01

    Para neoplastic cerebellar degeneration (PCD) is a type of para neoplastic neurological disorder (PND) that is associated with many solid tumors, Hodgkins lymphoma (HL) and very rarely with non-Hodgkin lymphoma (NHL). We report a case of PCD associated with gastric diffuse large B-cell lymphoma (DLBCL) in a patient who presented with acute onset of giddiness and double vision and had complete remission of the gastric lesion and marked improvement of cerebellar syndrome with rituximab-based combination chemotherapy. A brief review of the literature is also presented.

  17. A case of primary diffuse large B-cell non-Hodgkin's lymphoma misdiagnosed as chronic periapical periodontitis.

    Science.gov (United States)

    Jessri, M; AbdulMajeed, A A; Matias, M A; Farah, C S

    2013-06-01

    Lymphoma is a malignant neoplasm of component cells of the lymphoid system which is very rare in the jaws. Here we report a case of primary diffuse large B-cell lymphoma located in the periapical region of a mandibular molar which was misdiagnosed as chronic periapical periodontitis. The present case was diagnosed at an early stage and effectively managed by chemotherapy. Although lymphoma of the mandible is rare, it must be considered in the differential diagnosis of radiolucent lesions in this region. Lack of knowledge of this rare presentation may lead to delays in diagnosis and poor prognosis. © 2013 Australian Dental Association.

  18. CD19/CD22 Chimeric Antigen Receptor T Cells and Chemotherapy in Treating Patients With Recurrent or Refractory CD19 Positive Diffuse Large B-Cell Lymphoma or B Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2018-01-25

    B Acute Lymphoblastic Leukemia; CD19 Positive; Diffuse Large B-Cell Lymphoma Associated With Chronic Inflammation; Diffuse Large B-Cell Lymphoma, Not Otherwise Specified; Epstein-Barr Virus Positive Diffuse Large B-Cell Lymphoma of the Elderly; Minimal Residual Disease; Philadelphia Chromosome Positive; 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; T-Cell/Histiocyte-Rich Large B-Cell Lymphoma

  19. Routine imaging for diffuse large B-cell lymphoma in first remission is not associated with better survival

    DEFF Research Database (Denmark)

    El-Galaly, Tarec; Jakobsen, Lasse Hjort; Hutchings, Martin

    2015-01-01

    Background: Routine surveillance imaging plays a limited role in detecting recurrent diffuse large B-cell lymphoma (DLBCL), and the value of routine imaging is controversial. The present population-based study compares the post-remission survival of Danish and Swedish DLBCL patients-two neighbour......Background: Routine surveillance imaging plays a limited role in detecting recurrent diffuse large B-cell lymphoma (DLBCL), and the value of routine imaging is controversial. The present population-based study compares the post-remission survival of Danish and Swedish DLBCL patients...... are fully publicly funded. Follow-up (FU) for Swedish patients included symptom assessment, clinical examinations, and blood tests with 3-month intervals for 2 years and with longer intervals later in follow-up. Imaging was only performed in response to suspected relapse. FU for Danish patients...... was equivalent but included additional routine surveillance imaging (usually half-yearly CT for 2 years as a minimum). Clinico-pathological features were retrieved from the national lymphoma registries, and vital status was updated using the civil registries. OS was defined as the time from end of treatment...

  20. Terahertz Conductivity within Colloidal CsPbBr3 Perovskite Nanocrystals: Remarkably High Carrier Mobilities and Large Diffusion Lengths.

    Science.gov (United States)

    Yettapu, Gurivi Reddy; Talukdar, Debnath; Sarkar, Sohini; Swarnkar, Abhishek; Nag, Angshuman; Ghosh, Prasenjit; Mandal, Pankaj

    2016-08-10

    Colloidal CsPbBr3 perovskite nanocrystals (NCs) have emerged as an excellent light emitting material in last one year. Using time domain and time-resolved THz spectroscopy and density functional theory based calculations, we establish 3-fold free carrier recombination mechanism, namely, nonradiative Auger, bimolecular electron-hole recombination, and inefficient trap-assisted recombination in 11 nm sized colloidal CsPbBr3 NCs. Our results confirm a negligible influence of surface defects in trapping charge carriers, which in turn results into desirable intrinsic transport properties, from the perspective of device applications, such as remarkably high carrier mobility (∼4500 cm(2) V(-1) s(-1)), large diffusion length (>9.2 μm), and high luminescence quantum yield (80%). Despite being solution processed and possessing a large surface to volume ratio, this combination of high carrier mobility and diffusion length, along with nearly ideal photoluminescence quantum yield, is unique compared to any other colloidal quantum dot system.

  1. Intravascular Large B-Cell Lymphoma Presenting with Diffuse Gallbladder Wall Thickening: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Sayf Al-Katib

    2018-01-01

    Full Text Available Intravascular large B-cell lymphoma is a rare subtype of extranodal diffuse B-cell lymphoma characterized by proliferation of neoplastic cells within the lumen of small and medium sized vessels. Clinical and imaging findings are nebulous as the intravascular subtype of lymphoma can involve a multitude of organs. Involvement of the gallbladder is extremely uncommon, and imaging findings can be easily confused for more prevalent pathologies. We report a case of intravascular large B-cell lymphoma in an 83-year-old male and review clinical presentation and imaging findings on CT, ultrasound, hepatobiliary iminodiacetic acid (HIDA scan, and MRI. It is important for the radiologist to know about this disease as the imaging findings are atypical of other types of lymphoma, and this may lead to a delay in diagnosis and treatment.

  2. Accelerating inference for diffusions observed with measurement error and large sample sizes using approximate Bayesian computation

    DEFF Research Database (Denmark)

    Picchini, Umberto; Forman, Julie Lyng

    2016-01-01

    a nonlinear stochastic differential equation model observed with correlated measurement errors and an application to protein folding modelling. An approximate Bayesian computation (ABC)-MCMC algorithm is suggested to allow inference for model parameters within reasonable time constraints. The ABC algorithm......In recent years, dynamical modelling has been provided with a range of breakthrough methods to perform exact Bayesian inference. However, it is often computationally unfeasible to apply exact statistical methodologies in the context of large data sets and complex models. This paper considers...... applications. A simulation study is conducted to compare our strategy with exact Bayesian inference, the latter resulting two orders of magnitude slower than ABC-MCMC for the considered set-up. Finally, the ABC algorithm is applied to a large size protein data. The suggested methodology is fairly general...

  3. Primary Diffuse Large B-cell Lymphoma of the Uterus Manifesting as a Leiomyoma: A Unique Presentation with Review of Literature

    Directory of Open Access Journals (Sweden)

    Rajan Dewar

    2013-01-01

    Full Text Available We report a primary diffuse large B-cell lymphoma of uterine corpus in a 70-years old woman who presented with symptoms of increased urinary frequency and sense of bloating. Magnetic Resonance Imaging (MRI findings were suggestive of a degenerating intramural fibroid. Histological examination of tissue samples obtained during hysteroscopy showed diffuse infiltration of fibrous stroma by atypical enlarged mononuclear cells. Immunohistochemical studies were consistent with the diagnosis of diffuse large B-cell lymphoma.Further imaging studies showed no evidence of lymphoma outside the uterus. To our knowledge,this represents the first welldocumented case of primary uterine lymphoma presenting as a leiomyoma on imaging studies.

  4. Large fluctuations of the macroscopic current in diffusive systems: a numerical test of the additivity principle.

    Science.gov (United States)

    Hurtado, Pablo I; Garrido, Pedro L

    2010-04-01

    Most systems, when pushed out of equilibrium, respond by building up currents of locally conserved observables. Understanding how microscopic dynamics determines the averages and fluctuations of these currents is one of the main open problems in nonequilibrium statistical physics. The additivity principle is a theoretical proposal that allows to compute the current distribution in many one-dimensional nonequilibrium systems. Using simulations, we validate this conjecture in a simple and general model of energy transport, both in the presence of a temperature gradient and in canonical equilibrium. In particular, we show that the current distribution displays a Gaussian regime for small current fluctuations, as prescribed by the central limit theorem, and non-Gaussian (exponential) tails for large current deviations, obeying in all cases the Gallavotti-Cohen fluctuation theorem. In order to facilitate a given current fluctuation, the system adopts a well-defined temperature profile different from that of the steady state and in accordance with the additivity hypothesis predictions. System statistics during a large current fluctuation is independent of the sign of the current, which implies that the optimal profile (as well as higher-order profiles and spatial correlations) are invariant upon current inversion. We also demonstrate that finite-time joint fluctuations of the current and the profile are well described by the additivity functional. These results suggest the additivity hypothesis as a general and powerful tool to compute current distributions in many nonequilibrium systems.

  5. Large-scale fluctuations in the diffusive decomposition of solid solutions

    International Nuclear Information System (INIS)

    Karpov, V.G.; Grimsditch, M.

    1995-01-01

    The concept of an instability in the classic Ostwald ripening theory with respect to compositional fluctuations is suggested. We show that small statistical fluctuations in the precipitate phase lead to gigantic Coulomb-like fluctuations in the solute concentration which in turn affect the ripening. As a result large-scale fluctuations in both the precipitate and solute concentrations appear. These fluctuations are characterized by amplitudes of the order of the average values of the corresponding quantities and by a space scale L∼(na) -1/2 which is considerably greater than both the average nuclear radius and internuclear distance. The Lifshitz-Slyozov theory of ripening is shown to remain locally applicable, over length scales much less than L. The implications of these findings for elastic light scattering in solid solutions that have undergone Ostwald ripening are considered

  6. Large-scale fluctuations in the diffusive decomposition of solid solutions

    Science.gov (United States)

    Karpov, V. G.; Grimsditch, M.

    1995-04-01

    The concept of an instability in the classic Ostwald ripening theory with respect to compositional fluctuations is suggested. We show that small statistical fluctuations in the precipitate phase lead to gigantic Coulomb-like fluctuations in the solute concentration which in turn affect the ripening. As a result large-scale fluctuations in both the precipitate and solute concentrations appear. These fluctuations are characterized by amplitudes of the order of the average values of the corresponding quantities and by a space scale L~(na)-1/2 which is considerably greater than both the average nuclear radius and internuclear distance. The Lifshitz-Slyozov theory of ripening is shown to remain locally applicable, over length scales much less than L. The implications of these findings for elastic light scattering in solid solutions that have undergone Ostwald ripening are considered.

  7. Development of Spray on Bag for manufacturing of large composites parts: Diffusivity analysis

    Science.gov (United States)

    Dempah, Maxime Joseph

    Bagging materials are utilized in many composites manufacturing processes. The selection is mainly driven by cost, temperature requirements, chemical compatibility and tear properties of the bag. The air barrier properties of the bag are assumed to be adequate or in many cases are not considered at all. However, the gas barrier property of a bag is the most critical parameter, as it can negatively affect the quality of the final laminate. The barrier property is a function of the bag material, uniformity, thickness and temperature. Improved barrier properties are needed for large parts, high pressure consolidated components and structures where air stays entrapped on the part surface. The air resistance property of the film is defined as permeability and is investigated in this thesis. A model was developed to evaluate the gas transport through the film and an experimental cell was implemented to characterize various commercial films. Understanding and characterizing the transport phenomena through the film allows optimization of the bagging material for various manufacturing processes. Spray-on-Bag is a scalable alternative bagging method compared to standard films. The approach allows in-situ fabrication of the bag on large and complex geometry structures where optimization of the bag properties can be varied on a local level. An experimental setup was developed and implemented using a six axis robot and an automated spraying system. Experiments were performed on a flat surface and specimens were characterized and compared to conventional films. Air barrier properties were within range of standard film approaches showing the potential to fabricate net shape bagging structures in an automated process.

  8. [A morphometric analysis of the nuclei and nucleoli in tumor cells in lymphogranulomatosis, diffuse large B-cell lymphoma and anaplastic large cell lymphoma].

    Science.gov (United States)

    Gorgidze, L A; Vorob'ev, I A

    2009-01-01

    To make a comparative morphometric analysis of the nuclei and nucleoli of tumor cells in lymphogranulomatosis (LGM), diffuse large B-cell lymphoma (DLBCL) and anaplastic large cell lymphoma (ALCL) for differential diagnosis of these lymphomas. Biopsy material (lymph node biopsies) was frozen in hexane, fixed and stained, then microscopic pictures were made. Mean area of tumor cell nuclei in LGM was 97.25 +/- 68.77 mcm2, in DLBCL and ALCL--55.89 +/- 20.13 mcm2 and 70.31 +/- 34.64 mcm2, respectively. The area differences were significant (p nucleoli of the former are larger than those of the latter. Mean area of the nucleoli in DLBCL was 3.05 +/- 1.58, in ALCL--5.53 +/- 4.94 mcm2. The differences are significant (p Nucleoli in Hodgkin 's cells are significantly larger than those in the tumor cells in ALCL and DLBCL and the nucleoli with the area more than 12 mcm2 can be used in differential diagnosis between LGM and DLBCL but not between LGM and ALCL.

  9. Acute Respiratory Distress Syndrome Caused by Influenza B Virus Infection in a Patient with Diffuse Large B-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Silvio A. Ñamendys-Silva

    2011-01-01

    Full Text Available Influenza B virus infections are less common than infections caused by influenza A virus in critically ill patients, but similar mortality rates have been observed for both influenza types. Pneumonia caused by influenza B virus is uncommon and has been reported in pediatric patients and previously healthy adults. Critically ill patients with pneumonia caused by influenza virus may develop acute respiratory distress syndrome. We describe the clinical course of a critically ill patient with diffuse large B-cell lymphoma nongerminal center B-cell phenotype who developed acute respiratory distress syndrome caused by influenza B virus infection. This paper emphasizes the need to suspect influenza B virus infection in critically ill immunocompromised patients with progressive deterioration of cardiopulmonary function despite treatment with antibiotics. Early initiation of neuraminidase inhibitor and the implementation of guidelines for management of severe sepsis and septic shock should be considered.

  10. Multifocal Gastric Ulcers Caused by Diffuse Large B Cell Lymphoma in a Patient With Significant Weight Loss

    Directory of Open Access Journals (Sweden)

    Mark A. Gromski MD

    2016-12-01

    Full Text Available Primary gastrointestinal (GI lymphoma is a heterogeneous disease with varied clinical presentations. The stomach is the most common GI site and accounts for 70% to 75% of GI lymphomas. We present a patient with gastric diffuse large B cell lymphoma (DLBCL who presented with significant weight loss, early satiety, and multifocal ulcerated gastric lesions. Esophagoduodenoscopy should be performed in patients presenting with warning symptoms as in our case. Diagnosis is usually made by endoscopic biopsies. Multiple treatment modalities including surgery, radiotherapy, and chemotherapy have been used. Advancements in endoscopic and pathologic technology decrease turnaround time for diagnosis and treatment initiation, thus reducing the need for surgery. Health care providers should maintain a high level of suspicion and consider gastric DLBCL as part of the differential diagnosis, especially in those with warning symptoms such as weight loss and early satiety with abnormal endoscopic findings.

  11. Primary Diffuse Large B-Cell Lymphoma Localized to the Lacrimal Sac: A Case Presentation and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Kevin Zarrabi

    2016-01-01

    Full Text Available We report a rare case of diffuse large B-cell lymphoma (DLBCL of the lacrimal sac in a 50-year-old male. The incidence of primary ocular lymphoma is low and it is considered a rare disease. Moreover, reports of ocular DLBCL are uncommon and the disease remains poorly characterized. Our patient presented for management of osteomyelitis and was incidentally found to have a painless swelling and cyst around his right eye. A PET/CT scan revealed hypermetabolic activity within the lacrimal sac and a subsequent excisional biopsy of the mass yielded histopathology consistent with DLBCL. Consequently, the patient underwent treatment with R-CHOP therapy. The patient responded well to chemotherapy with a substantial shrinkage in tumor burden and the disease remained localized. Herein, we present a rare case of primary ocular lymphoma, highlight the importance of early diagnosis, and review current treatment modalities.

  12. Diabetes insipidus due to herpes encephalitis in a patient with diffuse large cell lymphoma. A case report.

    Science.gov (United States)

    Scheinpflug, K; Schalk, E; Reschke, K; Franke, A; Mohren, M

    2006-01-01

    The major causes of central diabetes insipidus are neoplastic or infiltrative lesions of the hypothalamus or pituitary, severe head injuries and pituitary or hypothalamic surgery. Central diabetes insipidus caused by viral infections has been rarely reported in immunosuppressed patients, such as those with acquired immunodeficiency syndrome or Cushing's syndrome. We report the case of a 48-year-old woman suffering from diffuse large cell lymphoma, who developed hypotonic polyuria, hypernatriaemia and somnolence after the first course of chemotherapy with CHOEP and rituximab. Diabetes insipidus was diagnosed by low urine osmolarity and an undetectable vasopressin concentration. MRI revealed no pituitary abnormalities but encephalitis, and lumbar punction confirmed herpes zoster infection. To the best of our knowledge this is the first description of central diabetes insipidus in a lymphoma patient caused by an opportunistic CNS-infection.

  13. Diffuse Large B-Cell Lymphoma in the Elderly: Real World Outcomes of Immunochemotherapy in Asian Population.

    Science.gov (United States)

    Byun, Ja Min; Lee, Jeong-Ok; Kang, Beodeul; Kim, Ji-Won; Kim, Se Hyun; Kim, Jin Won; Kim, Yu Jung; Lee, Keun-Wook; Bang, Soo-Mee; Lee, Jong Seok

    2016-09-01

    We evaluated the real-life treatment outcomes of elderly patients with diffuse large B-cell lymphoma from a homogenous Asian population and defined the cutoff age for "elderly." The medical records of 192 DLBCL patients aged > 60 years who had received first-line immunochemotherapy were retrospectively evaluated. The treatment schedule, adverse events, and survival outcomes were analyzed overall and stratified by 4 age groups (> 60-64, 65-69, 70-74, and ≥ 75 years). Patient age of ≥ 75 years was associated with a significantly lower complete remission rate (86.5% vs. 81.4% vs. 82.0% vs. 51%; P population, 75 years seems to be a judicious cutoff for predicting treatment outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Advances in the molecular diagnosis of diffuse large B-cell lymphoma in the era of precision medicine.

    Science.gov (United States)

    Araf, Shamzah; Korfi, Koorosh; Rahim, Tahrima; Davies, Andrew; Fitzgibbon, Jude

    2016-10-01

    The adoption of high-throughput technologies has led to a transformation in our ability to classify diffuse large B-cell lymphoma (DLBCL) into unique molecular subtypes. In parallel, the expansion of agents targeting key genetic and gene expression signatures has led to an unprecedented opportunity to personalize cancer therapies, paving the way for precision medicine. Areas covered: This review summarizes the key molecular subtypes of DLBCL and outlines the novel technology platforms in development to discriminate clinically relevant subtypes. Expert commentary: The application of emerging diagnostic tests into routine clinical practise is gaining momentum following the demonstration of subtype specific activity by novel agents. Co-ordinated efforts are required to ensure that these state of the art technologies provide reliable and clinically meaningful results accessible to the wider haematology community.

  15. First-principles studies on vacancy-modified interstitial diffusion mechanism of oxygen in nickel, associated with large-scale atomic simulation techniques

    International Nuclear Information System (INIS)

    Fang, H. Z.; Shang, S. L.; Wang, Y.; Liu, Z. K.; Alfonso, D.; Alman, D. E.; Shin, Y. K.; Zou, C. Y.; Duin, A. C. T. van; Lei, Y. K.; Wang, G. F.

    2014-01-01

    This paper is concerned with the prediction of oxygen diffusivities in fcc nickel from first-principles calculations and large-scale atomic simulations. Considering only the interstitial octahedral to tetrahedral to octahedral minimum energy pathway for oxygen diffusion in fcc lattice, greatly underestimates the migration barrier and overestimates the diffusivities by several orders of magnitude. The results indicate that vacancies in the Ni-lattice significantly impact the migration barrier of oxygen in nickel. Incorporation of the effect of vacancies results in predicted diffusivities consistent with available experimental data. First-principles calculations show that at high temperatures the vacancy concentration is comparable to the oxygen solubility, and there is a strong binding energy and a redistribution of charge density between the oxygen atom and vacancy. Consequently, there is a strong attraction between the oxygen and vacancy in the Ni lattice, which impacts diffusion

  16. Loss of PRDM1/BLIMP-1 function contributes to poor prognosis of activated B-cell-like diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Xia, Yi; Xu-Monette, Z Y; Tzankov, A

    2017-01-01

    PRDM1/BLIMP-1, a master regulator of plasma-cell differentiation, is frequently inactivated in activated B-cell-like (ABC) diffuse large B-cell lymphoma (DLBCL) patients. Little is known about its genetic aberrations and relevant clinical implications. A large series of patients with de novo DLBC...

  17. MDM2 phenotypic and genotypic profiling, respective to TP53 genetic status, in diffuse large B-cell lymphoma patients treated with rituximab-CHOP immunochemotherapy

    DEFF Research Database (Denmark)

    Xu-Monette, Zijun Y; Møller, Michael B; Tzankov, Alexander

    2013-01-01

    MDM2 is a key negative regulator of the tumor suppressor p53, however, the prognostic significance of MDM2 overexpression in diffuse large B-cell lymphoma (DLBCL) has not been defined convincingly. In a p53 genetically-defined large cohort of de novo DLBCL patients treated with rituximab, cycloph...

  18. A finite element simulation on transient large deformation and mass diffusion in electrodes for lithium ion batteries

    International Nuclear Information System (INIS)

    An, Yonghao; Jiang, Hanqing

    2013-01-01

    Lithium-ion batteries have attracted great deal of attention recently. Silicon is one of the most promising anode materials for high-performance lithium-ion batteries, due to its highest theoretical specific capacity. However, the short lifetime confined by mechanical failure in the silicon anode is now considered to be the biggest challenge in desired applications. High stress induced by the huge volume change due to lithium insertion/extraction is the main reason underlying this problem. Some theoretical models have been developed to address this issue. In order to properly implement these models, we develop a finite element based numerical method using a commercial software package, ABAQUS, as a platform at the continuum level to study fully coupled large deformation and mass diffusion problem. Using this method, large deformation, elasticity–plasticity of the electrodes, various spatial and temporal conditions, arbitrary geometry and dimension could be fulfilled. The interaction between anode and other components of the lithium ion batteries can also be studied as an integrated system. Several specific examples are presented to demonstrate the capability of this numerical platform. (paper)

  19. PIK3CA expression in diffuse large B cell lymphoma tissue and the effect of its knockdown in vitro

    Directory of Open Access Journals (Sweden)

    Cui W

    2017-04-01

    Full Text Available Wenli Cui,1–4,* Shutao Zheng,5,6,* Zebing Liu,1–3 Weige Wang,1–3 Ying Cai,1–3 Rui Bi,1–3 Bing Cao,1–3 Xiaoyan Zhou1–3 1Department of Pathology, Shanghai Cancer Center, Fudan University, 2Department of Oncology, Shanghai Medical College, Fudan University, 3Institute of Pathology, Fudan University, Shanghai, 4Department of Pathology, The First Affiliated Hospital of Xinjiang Medical University, 5Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, 6State Key Lab Incubation Base of Xinjiang Major Diseases Research, First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi, People’s Republic of China *These authors contributed equally to this work Abstract: PIK3CA has been extensively investigated from its molecular mechanism perspective and epidemiological association with its mutations in different types of cancers. However, little has been reported regarding the clinicopathological significance of PIK3CA expression in diffuse large B cell lymphoma (DLBCL. In the present study, we investigated the clinicopathological significance of PIK3CA in DLBCL by performing immunohistochemical evaluation of PIK3CA in tissue microarrays consisting of 199 cases of DLBCL. Kaplan–Meier survival analysis was performed to analyze the association between PIK3CA expression and overall prognosis. To further investigate the role of PIK3CA mediated in the proliferation, cell cycle and apoptosis of DLBCL cells, Cell Counting Kit-8 (CCK-8 and flow cytometry assays were carried out in DLBCL cell lines after successful, stable knockdown of PIK3CA using lentiviral short hairpin RNA inference. Our results indicated that although PIK3CA was shown to be extensively expressed in DLBCL, no significant association was observed between PIK3CA expression and clinical outcome or between PIK3CA expression and other clinicopathological parameters, except between performance state (PS

  20. Combination of Bcl-2 and MYC protein expression improves high-risk stratification in diffuse large B-cell lymphoma

    Directory of Open Access Journals (Sweden)

    Wang J

    2015-09-01

    Full Text Available Jing Wang,* Min Zhou,* Jing-Yan Xu,* Bing Chen, Jian OuyangDepartment of Hematology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, People’s Republic of China*These authors contributed equally to this work and should be considered as cofirst authorsPurpose: To evaluate whether the addition of two biological markers (MYC and BCL-2 protein overexpression improves the stratification of high-risk patients with diffuse large B-cell lymphoma (DLBCL.Method: Seven risk factors were identified at diagnosis, and a maximum of 7 points were assigned to each patient. The patients were classified according to four risk groups: low (0–1, low-intermediate (2–3, high-intermediate (4, and high (5–7. Only high-risk patients with DLBCL were included in this analysis. We retrospectively examined 20 cases from 2008 to 2013 at the Nanjing Drum Tower Hospital.Results: The median expression of MYC protein was 60%, and 17 of 20 (65% evaluable cases overexpressed MYC. The median expression of BCL-2 protein was also 60%. Eighteen of 20 (90% evaluable cases showed BCL-2 overexpression. Additionally, 12 out of 20 cases (60% demonstrated coexpression of MYC and BCL-2 proteins. The percentages of overall survival and progression-free survival at the median follow-up time (36 months were 33.3%±16.1% and 16.9%±13.5%, respectively. By comparison, nine, four, and 20 patients were classified as high risk based on the International Prognostic Index (IPI, National Comprehensive Cancer Network(NCCN-IPI, and revised IPI criteria, respectively. According to the IPI and NCCN-IPI stratification, the risk groups demonstrated closely overlapping survival curves. In addition, four out of 20 cases were identified as low-intermediate risk according to the NCCN-IPI criteria.Conclusion: The addition of MYC and BCL-2 protein expression to the IPI could identify a subset of DLBCL patients with high-risk clinicopathological characteristics and

  1. Role of microRNAs and microRNA machinery in the pathogenesis of diffuse large B-cell lymphoma

    International Nuclear Information System (INIS)

    Caramuta, S; Lee, L; Özata, D M; Akçakaya, P; Georgii-Hemming, P; Xie, H; Amini, R-M; Lawrie, C H; Enblad, G; Larsson, C; Berglund, M; Lui, W-O

    2013-01-01

    Deregulation of microRNA (miRNA) expression has been documented in diffuse large B-cell lymphoma (DLBCL). However, the impact of miRNAs and their machinery in DLBCL is not fully determined. Here, we assessed the role of miRNA expression and their processing genes in DLBCL development. Using microarray and RT-qPCR approaches, we quantified global miRNAs and core components of miRNA-processing genes expression in 75 DLBCLs (56 de novo and 19 transformed) and 10 lymph nodes (LN). Differential miRNA signatures were identified between DLBCLs and LNs, or between the de novo and transformed DLBCLs. We also identified subsets of miRNAs associated with germinal center B-cell phenotype, BCL6 and IRF4 expression, and clinical staging. In addition, we showed a significant over-expression of TARBP2 in de novo DLBCLs as compared with LNs, and decreased expression of DROSHA, DICER, TARBP2 and PACT in transformed as compared with de novo cases. Interestingly, cases with high TARBP2 and DROSHA expression had a poorer chemotherapy response. We further showed that TARBP2 can regulate miRNA-processing efficiency in DLBCLs, and its expression inhibition decreases cell growth and increases apoptosis in DLBCL cell lines. Our findings provide new insights for the understanding of miRNAs and its machinery in DLBCL

  2. Elevated serum IL-10 levels in diffuse large B-cell lymphoma: a mechanism of aberrant JAK2 activation.

    Science.gov (United States)

    Gupta, Mamta; Han, Jing Jing; Stenson, Mary; Maurer, Matthew; Wellik, Linda; Hu, Guangzhen; Ziesmer, Steve; Dogan, Ahmet; Witzig, Thomas E

    2012-03-22

    Cytokines are deregulated in cancers and can contribute to tumor growth. In patients with diffuse large-cell lymphoma (DLBCL), we observed higher levels of JAK/STAT pathway-related serum cytokines (ie, IL-6, IL-10, epidermal growth factor, and IL-2) compared with controls. Of these, only IL-10 activated the JAK2 pathway in lymphoma cells in vitro. Patients with high serum IL-10 had shorter event-free survival (EFS) than patients with low levels (P > .01) and high IL-10 was correlated with high lactase dehydrogenase (P = .0085) and higher International Prognostic Index scores (P = .01). To explore the mechanism by which IL-10 may contribute to an inferior EFS, we investigated the effect of IL-10 on the JAK2 pathway and found that the IL-10/IL-10 receptor complex up-regulated JAK2 signaling. Neutralizing Ab to IL-10 inhibited constitutive and IL-10-induced JAK2/STAT3 phosphorylation. JAK2 inhibition dephosphorylated JAK2 and STAT3 and caused an inhibitory effect on phospho-JAK2-positive DLBCL cells; there was a minimal effect on phospho-JAK2-negative cells. Apoptosis induced by JAK2 inhibition was dependent on inhibition of autocrine IL-10 and c-myc expression and independent of Bcl-2 family expression. These results provide the rationale for testing JAK2 inhibitors in DLBCL patients, and indicate that serum IL-10 may be a biomarker to identify patients more likely to respond to JAK2-targeted therapy.

  3. A rare case of anasarca caused by infiltration of the pituitary gland by diffuse large B-cell lymphoma.

    Science.gov (United States)

    Kumabe, Ayako; Kenzaka, Tsuneaki; Nishimura, Yoshioki; Aikawa, Masaki; Mori, Masaki; Matsumura, Masami

    2015-03-25

    Anasarca in patients with lymphoma is a rare symptom. We report a patient with DLBCL associated with pituitary gland infiltration that was diagnosed based on significant anasarca. A 72-year-old woman with a 10-year history of hypertension visited a local hospital presenting with anasarca and 15-kg weight gain in the past 3 months. we clinically diagnosed central hypothyroidism caused by pituitary gland infiltration of diffuse large B-cell lymphoma (DLBCL) (clinical stage IV in the Ann Arbor staging classification). The first course of chemotherapy improved anasarca remarkably and the patient's body weight returned to what it was 3 months before. We experienced a patient with remarkable anasarca caused by DLBCL infiltration of the pituitary gland. A pituitary gland lesion with central hypothyroidism should be considered as one of the differential diagnoses of edema. This case was very valuable because we could assess it by following the time course of symptoms (edema and delayed relaxation time of the Achilles tendon reflex), laboratory data, and imaging findings (swelling anterior pituitary lobe).

  4. Numerical and analytical approaches to an advection-diffusion problem at small Reynolds number and large Péclet number

    Science.gov (United States)

    Fuller, Nathaniel J.; Licata, Nicholas A.

    2018-05-01

    Obtaining a detailed understanding of the physical interactions between a cell and its environment often requires information about the flow of fluid surrounding the cell. Cells must be able to effectively absorb and discard material in order to survive. Strategies for nutrient acquisition and toxin disposal, which have been evolutionarily selected for their efficacy, should reflect knowledge of the physics underlying this mass transport problem. Motivated by these considerations, in this paper we discuss the results from an undergraduate research project on the advection-diffusion equation at small Reynolds number and large Péclet number. In particular, we consider the problem of mass transport for a Stokesian spherical swimmer. We approach the problem numerically and analytically through a rescaling of the concentration boundary layer. A biophysically motivated first-passage problem for the absorption of material by the swimming cell demonstrates quantitative agreement between the numerical and analytical approaches. We conclude by discussing the connections between our results and the design of smart toxin disposal systems.

  5. Similar prognosis of transformed and de novo diffuse large B-cell lymphomas in patients treated with immunochemotherapy.

    Science.gov (United States)

    Sorigue, Marc; Garcia, Olga; Baptista, Maria Joao; Sancho, Juan-Manuel; Tapia, Gustavo; Mate, José Luis; Feliu, Evarist; Navarro, José-Tomás; Ribera, Josep-Maria

    2017-03-22

    The prognosis of diffuse large B-cell lymphomas (DLBCL) transformed from indolent lymphoma (TL) has been considered poorer than that of de novo DLBCL. However, it seems to have improved since the introduction of rituximab. We compared the characteristics (including the cell-of-origin), and the prognosis of 29 patients with TL and 101 with de novo DLBCL treated with immunochemotherapy. Patients with TL and de novo DLBCL had similar characteristics. All TL cases evolving from follicular lymphoma were germinal-center B-cell-like, while those TL from marginal zone lymphoma or chronic lymphocytic leukemia were non-germinal-center B-cell-like. The complete response rate was similar in TL and de novo DLBCL (62 vs. 66%, P=.825). The 5-year overall and progression-free survival probabilities (95% CI) were 59% (40-78) and 41% (22-60) for TL and 63% (53-73) and 60% (50-70) for de novo DLBCL, respectively (P=.732 for overall survival and P=.169 for progression-free survival). In this study, the prognosis of TL and de novo DLBCL treated with immunochemotherapy was similar. The role of intensification with stem cell transplantation in the management of TL may be questionable in the rituximab era. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  6. Data-Driven Diffusion Of Innovations: Successes And Challenges In 3 Large-Scale Innovative Delivery Models.

    Science.gov (United States)

    Dorr, David A; Cohen, Deborah J; Adler-Milstein, Julia

    2018-02-01

    Failed diffusion of innovations may be linked to an inability to use and apply data, information, and knowledge to change perceptions of current practice and motivate change. Using qualitative and quantitative data from three large-scale health care delivery innovations-accountable care organizations, advanced primary care practice, and EvidenceNOW-we assessed where data-driven innovation is occurring and where challenges lie. We found that implementation of some technological components of innovation (for example, electronic health records) has occurred among health care organizations, but core functions needed to use data to drive innovation are lacking. Deficits include the inability to extract and aggregate data from the records; gaps in sharing data; and challenges in adopting advanced data functions, particularly those related to timely reporting of performance data. The unexpectedly high costs and burden incurred during implementation of the innovations have limited organizations' ability to address these and other deficits. Solutions that could help speed progress in data-driven innovation include facilitating peer-to-peer technical assistance, providing tailored feedback reports to providers from data aggregators, and using practice facilitators skilled in using data technology for quality improvement to help practices transform. Policy efforts that promote these solutions may enable more rapid uptake of and successful participation in innovative delivery system reforms.

  7. Large eddy simulation of turbulent diffusion flame with hybrid fuel of CH4/H2 in various background conditions

    Science.gov (United States)

    Hong, Sungmin; Lee, Wook; Song, Han Ho; Kang, Seongwon

    2014-11-01

    A turbulent diffusion flame with hybrid fuel of methane and hydrogen is analyzed to investigate the effects of operating conditions on flame shape, rate of fuel consumption and pollutant formation. Various combinations of operating parameter, i.e. hydrogen concentration, background pressure and temperature, are examined in relatively high pressure and temperature conditions that can be found at the end of compression stroke in an internal combustion engine. A flamelet-progress variable approach (FPVA) and a dynamic subgrid scale (SGS) model are used for large eddy simulation (LES). A comparison with previous experiments and simulations in the standard condition shows a good agreement in the statistics of flow fields and chemical compositions, as well as in the resultant trends by similar parametric studies. As a result, the effects of added hydrogen are found to be consistent for most of the chemical species in the range of background pressure and temperature conditions. However, the flow fields of some species such as OH, NO, CO at a higher pressure and temperature state show a behavior different from the standard condition. Finally, hydrogen addition is shown to improve flame stability which is measured by the pressure fluctuations in all the tested conditions.

  8. Metabolic fingerprinting of fresh lymphoma samples used to discriminate between follicular and diffuse large B-cell lymphomas.

    Science.gov (United States)

    Barba, Ignasi; Sanz, Carolina; Barbera, Angels; Tapia, Gustavo; Mate, José-Luis; Garcia-Dorado, David; Ribera, Josep-Maria; Oriol, Albert

    2009-11-01

    To investigate if proton nuclear magnetic resonance ((1)H NMR) spectroscopy-based metabolic profiling was able to differentiate follicular lymphoma (FL) from diffuse large B-cell lymphoma (DLBCL) and to study which metabolites were responsible for the differences. High-resolution (1)H NMR spectra was obtained from fresh samples of lymph node biopsies obtained consecutively at one center (14 FL and 17 DLBCL). Spectra were processed using pattern-recognition methods. Discriminant models were able to differentiate between the two tumor types with a 86% sensitivity and a 76% specificity; the metabolites that most contributed to the discrimination were a relative increase of alanine in the case of DLBCL and a relative increase of taurine in FL. Metabolic models had a significant but weak correlation with Ki67 expression (r(2)=0.42; p=0.002) We have proved that it is possible to differentiate between FL and DLBCL based on their NMR metabolic profiles. This approach may potentially be applicable as a noninvasive tool for diagnostic and treatment follow-up in the clinical setting using conventional magnetic resonance systems.

  9. Gene Mutation Profiles in Primary Diffuse Large B Cell Lymphoma of Central Nervous System: Next Generation Sequencing Analyses

    Science.gov (United States)

    Todorovic Balint, Milena; Jelicic, Jelena; Mihaljevic, Biljana; Kostic, Jelena; Stanic, Bojana; Balint, Bela; Pejanovic, Nadja; Lucic, Bojana; Tosic, Natasa; Marjanovic, Irena; Stojiljkovic, Maja; Karan-Djurasevic, Teodora; Perisic, Ognjen; Rakocevic, Goran; Popovic, Milos; Raicevic, Sava; Bila, Jelena; Antic, Darko; Andjelic, Bosko; Pavlovic, Sonja

    2016-01-01

    The existence of a potential primary central nervous system lymphoma-specific genomic signature that differs from the systemic form of diffuse large B cell lymphoma (DLBCL) has been suggested, but is still controversial. We investigated 19 patients with primary DLBCL of central nervous system (DLBCL CNS) using the TruSeq Amplicon Cancer Panel (TSACP) for 48 cancer-related genes. Next generation sequencing (NGS) analyses have revealed that over 80% of potentially protein-changing mutations were located in eight genes (CTNNB1, PIK3CA, PTEN, ATM, KRAS, PTPN11, TP53 and JAK3), pointing to the potential role of these genes in lymphomagenesis. TP53 was the only gene harboring mutations in all 19 patients. In addition, the presence of mutated TP53 and ATM genes correlated with a higher total number of mutations in other analyzed genes. Furthermore, the presence of mutated ATM correlated with poorer event-free survival (EFS) (p = 0.036). The presence of the mutated SMO gene correlated with earlier disease relapse (p = 0.023), inferior event-free survival (p = 0.011) and overall survival (OS) (p = 0.017), while mutations in the PTEN gene were associated with inferior OS (p = 0.048). Our findings suggest that the TP53 and ATM genes could be involved in the molecular pathophysiology of primary DLBCL CNS, whereas mutations in the PTEN and SMO genes could affect survival regardless of the initial treatment approach. PMID:27164089

  10. The Impact of Drug Metabolism Gene Polymorphisms on Therapeutic Response and Survival in Diffuse Large B-Cell Lymphoma Patients.

    Science.gov (United States)

    Pál, Ildikó; Illés, Árpád; Gergely, Lajos; Pál, Tibor; Radnay, Zita; Szekanecz, Zoltán; Zilahi, Erika; Váróczy, László

    2018-04-01

    Diffuse large B-cell lymphoma (DLBCL) accounts for 30% of all non-Hodgkin lymphomas (NHL) and 80% of agressive lymphomas. Besides the traditional International Prognostic Index (IPI), some other factors may also influence the prognosis of DLBCL patients. To study how the genetic polymorphisms in the metabolic pathway influence the event-free and overall survivals and therapeutic responses in DLBCL. The study was comprised of 51 patients (32 men, 19 women). The average age was 53.1 years. DLBCL was diagnosed between 2011 and 2016 and the average follow-up time was 3.78 years. These patients received 1-8 cycles (an average of 6.2 cycles) of rituximab, cyclophosphamide, doxorubicin, vincristin, prednisolon (R-CHOP) immunochemotherapy. Real-time polymerase chain reaction was used to determine the genetic polymorphisms of CYP2E1, GSTP1, NAT1, and NAT2 genes. Our results showed that the polymorphisms of CYP2E1, GSTP1, and NAT1 genes did not influence the prognosis of DLBCL patients significantly. In terms of the NAT2 gene, GG homozygous patients showed slightly better therapeutic response and survival results compared to those bearing an A allele; however, the differences were not statistically significant. Our results could not confirm that genetic polymorphism in metabolic pathways has any predictive role in DLBCL.

  11. Pretherapy metabolic tumour volume is an independent predictor of outcome in patients with diffuse large B-cell lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Sasanelli, Myriam; Meignan, Michel; Haioun, Corinne; Itti, Emmanuel [Paris-Est University, Nuclear Medicine and Lymphoid Malignancies Unit, Henri Mondor Hospital, Creteil (France); Berriolo-Riedinger, Alina; Casasnovas, Rene-Olivier [Nuclear Medicine and Hematology, Georges-Francois Leclerc Center, Le Bocage Hospital, Dijon (France); Biggi, Alberto; Gallamini, Andrea [Nuclear Medicine and Hematology, Santa Croce e Carle Hospital, Cuneo (Italy); Siegel, Barry A.; Cashen, Amanda F. [Washington University School of Medicine, Nuclear Medicine and Oncology, Siteman Cancer Center, St. Louis, MO (United States); Vera, Pierre; Tilly, Herve [Nuclear Medicine and Hematology, Henri Becquerel Center, Rouen (France); Versari, Annibale [Nuclear Medicine, Santa Maria Nuova Hospital-IRCCS, Reggio Emilia (Italy)

    2014-11-15

    We investigated the prognostic value of total metabolic tumour volume (TMTV) in diffuse large B-cell lymphoma (DLBCL). TMTV was measured in 114 patients with newly diagnosed DLBCL who underwent {sup 18}F-FDG PET/CT at baseline before immunochemotherapy. TMTV was computed by summing the volumes of all lymphomatous lesions after applying the local SUVmax threshold of 41 % using semiautomatic software. Prognostic value was assessed by Kaplan-Meier estimates of progression-free survival (PFS) and overall survival (OS). Median follow-up was 39 months. Average pretherapy TMTV was 509 ± 568 cm{sup 3}. The 3-year estimates of PFS were 77 % in the low metabolic burden group (TMTV ≤550 cm{sup 3}) and 60 % in the high metabolic burden group (TMTV >550 cm{sup 3}, p = 0.04), and prediction of OS was even better (87 % vs. 60 %, p = 0.0003). Cox regression showed independence of TMTV for OS prediction (p = 0.002) compared with other pretherapy indices of tumour burden, such as tumour bulk and the International Prognostic Index. Pretherapy TMTV is an independent predictor of outcome in patients with DLBCL. (orig.)

  12. Contemporary conceptions of etiology, pathogenesis, management and treatment of primary diffuse large b-cell central nervous system lymphoma

    Directory of Open Access Journals (Sweden)

    S. V. Voloshin

    2013-01-01

    Full Text Available In this article we present the most up-to-date information about etiology, pathogenesis, diagnostic and treatment principles of primary central nervous system diffuse large B-cell lymphoma. We propose algorithm of diagnosis and treatment based on literature review and own experience. The main methods for diagnosis verification are magneto-resonance tomography and stereotactic biopsy of mass with subsequent histological examination including immune staining. The common first-line therapy regimen is high-dose methotrexate therapy. However long-term prognosis still remains poor. Adverse prognostic factors for therapy response are age > 60 years, multifocal lesions, neurologic symptoms,previous treated disease. Considerable part of patient have contraindications or high-risk of adverse events for high-dose chemotherapy treatment. Anti-CD20 monoclonal antibody has no neurological toxicity with intravenous and intrathecal administrations. Combination therapy with reduced dose methotrexate and monoclonal antibody can be a reasonable treatment alternative for old and disable persons. The further survival improvement would be achieved by patient stratification and using of risk-adapted treatment algorithm. 

  13. Contemporary conceptions of etiology, pathogenesis, management and treatment of primary diffuse large b-cell central nervous system lymphoma

    Directory of Open Access Journals (Sweden)

    S. V. Voloshin

    2014-07-01

    Full Text Available In this article we present the most up-to-date information about etiology, pathogenesis, diagnostic and treatment principles of primary central nervous system diffuse large B-cell lymphoma. We propose algorithm of diagnosis and treatment based on literature review and own experience. The main methods for diagnosis verification are magneto-resonance tomography and stereotactic biopsy of mass with subsequent histological examination including immune staining. The common first-line therapy regimen is high-dose methotrexate therapy. However long-term prognosis still remains poor. Adverse prognostic factors for therapy response are age > 60 years, multifocal lesions, neurologic symptoms,previous treated disease. Considerable part of patient have contraindications or high-risk of adverse events for high-dose chemotherapy treatment. Anti-CD20 monoclonal antibody has no neurological toxicity with intravenous and intrathecal administrations. Combination therapy with reduced dose methotrexate and monoclonal antibody can be a reasonable treatment alternative for old and disable persons. The further survival improvement would be achieved by patient stratification and using of risk-adapted treatment algorithm. 

  14. Evidence of solitary chemosensory cells in a large mammal: the diffuse chemosensory system in Bos taurus airways

    Science.gov (United States)

    Tizzano, Marco; Merigo, Flavia; Sbarbati, Andrea

    2006-01-01

    The diffuse chemosensory system (DCS) of the respiratory apparatus is composed of solitary chemosensory cells (SCCs) that resemble taste cells but are not organized in end organs. The discovery of the DCS may open up new approaches to respiratory diseases. However, available data on mammalian SCCs have so far been collected from rodents, the airways of which display some differences from those of large mammals. Here we investigated the presence of the DCS and of SCCs in cows and bulls (Bos taurus), in which the airway cytology is similar to that in humans, focusing our attention on detection in the airways of molecules involved in the transduction cascade of taste [i.e. α-gustducin and phospholipase C of the β2 subtype (PLCβ2)]. The aim of the research was to extend our understanding of airway chemoreceptors and to compare the organization of the DCS in a large mammal with that in rodents. Using immunocytochemistry for α-gustducin, the taste buds of the tongue and arytenoid were visualized. In the trachea and bronchi, α-gustducin-immunoreactive SCCs were frequently found. Using immunocytochemistry for PLCβ2, the staining pattern was generally similar to those seen for α-gustducin. Immunoblotting confirmed the expression of α-gustducin in the tongue and in all the airway regions tested. The study demonstrated the presence of SCCs in cows and bulls, suggesting that DCSs are present in many mammalian species. The description of areas with a high density of SCCs in bovine bronchi seems to indicate that the view of the DCS as made up of isolated cells totally devoid of ancillary elements is probably an oversimplification. PMID:16928202

  15. Analysis and experimental study on formation conditions of large-scale barrier-free diffuse atmospheric pressure air plasmas in repetitive pulse mode

    Science.gov (United States)

    Li, Lee; Liu, Lun; Liu, Yun-Long; Bin, Yu; Ge, Ya-Feng; Lin, Fo-Chang

    2014-01-01

    Atmospheric air diffuse plasmas have enormous application potential in various fields of science and technology. Without dielectric barrier, generating large-scale air diffuse plasmas is always a challenging issue. This paper discusses and analyses the formation mechanism of cold homogenous plasma. It is proposed that generating stable diffuse atmospheric plasmas in open air should meet the three conditions: high transient power with low average power, excitation in low average E-field with locally high E-field region, and multiple overlapping electron avalanches. Accordingly, an experimental configuration of generating large-scale barrier-free diffuse air plasmas is designed. Based on runaway electron theory, a low duty-ratio, high voltage repetitive nanosecond pulse generator is chosen as a discharge excitation source. Using the wire-electrodes with small curvature radius, the gaps with highly non-uniform E-field are structured. Experimental results show that the volume-scaleable, barrier-free, homogeneous air non-thermal plasmas have been obtained between the gap spacing with the copper-wire electrodes. The area of air cold plasmas has been up to hundreds of square centimeters. The proposed formation conditions of large-scale barrier-free diffuse air plasmas are proved to be reasonable and feasible.

  16. Assessment of CD37 B-cell antigen and cell of origin significantly improves risk prediction in diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Xu-Monette, Zijun Y; Li, Ling; Byrd, John C

    2016-01-01

    CD37 (tetraspanin TSPAN26) is a B-cell surface antigen widely expressed on mature B cells. CD37 is involved in immune regulation and tumor suppression but its function has not been fully elucidated. We assessed CD37 expression in de novo diffuse large B-cell lymphoma (DLBCL), and investigated its...

  17. Prognostic value of interim FDG-PET in R-CHOP-treated diffuse large B-cell lymphoma : Systematic review and meta-analysis

    NARCIS (Netherlands)

    Adams, Hugo J A; Kwee, Thomas C.

    2016-01-01

    This study aimed to systematically review and meta-analyze the prognostic value of interim 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone

  18. Prognostic impact of germinal center-associated proteins and chromosomal breakpoints in poor-risk diffuse large B-cell lymphoma

    NARCIS (Netherlands)

    van Imhoff, Gustaaf W.; Boerma, Evert-Jan G.; van der Holt, Bronno; Schuuring, Ed; Verdonck, Leo F.; Kluin-Nelemans, Hanneke C.; Kluin, Philip M.

    2006-01-01

    Purpose Outcome of diffuse large B-cell lymphoma (DLBCL) with a germinal center B-cell (GCB) expression profile is superior to that of non-GCB DLBCL. This conclusion is mainly derived from patients with mixed international prognostic index (IPI) risk profiles treated with CHOP-like therapy

  19. Identification of relevant drugable targets in diffuse large B-cell lymphoma using a genome-wide unbiased CD20 guilt-by association approach

    NARCIS (Netherlands)

    de Jong, Mathilde R. W.; Visser, Lydia; Huls, Gerwin; Diepstra, Arjan; van Vugt, Marcel; Ammatuna, Emanuele; van Rijn, Rozemarijn S.; Vellenga, Edo; van den Berg, Anke; Fehrmann, Rudolf S. N.; van Meerten, Tom

    2018-01-01

    Forty percent of patients with diffuse large B-cell lymphoma (DLBCL) show resistant disease to standard chemotherapy (CHOP) in combination with the anti-CD20 monoclonal antibody rituximab (R). Although many new anti-cancer drugs were developed in the last years, it is unclear which of these drugs

  20. Mutational profile and prognostic significance of TP53 in diffuse large B-cell lymphoma patients treated with R-CHOP

    DEFF Research Database (Denmark)

    Xu-Monette, Zijun Y; Wu, Lin; Visco, Carlo

    2012-01-01

    TP53 mutation is an independent marker of poor prognosis in patients with diffuse large B-cell lymphoma (DLBCL) treated with cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone (CHOP) therapy. However, its prognostic value in the rituximab immunochemotherapy era remains undefined. ...... for stratifying R-CHOP-treated patients into distinct prognostic subsets and has significant value in the design of future therapeutic strategies....

  1. The number of extranodal sites assessed by PET/CT scan is a powerful predictor of CNS relapse for patients with diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    El-Galaly, Tarec Christoffer; Villa, Diego; Michaelsen, Thomas Yssing

    2017-01-01

    Purpose Development of secondary central nervous system involvement (SCNS) in patients with diffuse large B-cell lymphoma is associated with poor outcomes. The CNS International Prognostic Index (CNS-IPI) has been proposed for identifying patients at greatest risk, but the optimal model is unknow...

  2. The value of routine bone marrow biopsy in patients with diffuse large B-cell lymphoma staged with PET/CT

    DEFF Research Database (Denmark)

    Alzahrani, M; El-Galaly, T C; Hutchings, M

    2016-01-01

    BACKGROUND: The added diagnostic and prognostic value of routine bone marrow biopsy (BMB) in patients with diffuse large B-cell lymphoma (DLBCL) undergoing positron emission tomography combined with computed tomography (PET/CT) staging is controversial. PATIENTS AND METHODS: Patients with newly d...

  3. Addition of rituximab to chemotherapy overcomes the negative prognostic impact of cyclin E expression in diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Frei, E; Visco, C; Xu-Monette, Z Y

    2013-01-01

    High levels of cyclin E (CCNE) are accompanied by shorter survival in cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone (CHOP)-treated diffuse large B-cell lymphomas (DLBCL), independent of the international prognostic index (IPI). Data on the prognostic role of CCNE in the 'rituximab...

  4. Very late relapse in diffuse large B-cell lymphoma represents clonally related disease and is marked by germinal center cell features

    NARCIS (Netherlands)

    de Jong, Daphne; Glas, Annuska M.; Boerrigter, Lucie; Hermus, Marie-Christine; Dalesio, Otilia; Willemse, Els; Nederlof, Petra M.; Kersten, Marie José

    2003-01-01

    Patients with diffuse large B-cell lymphoma (DLBCL) rarely show relapse after 4 years of complete remission (CR). In this study, we addressed the following questions: (1) Does late-relapsing DLBCL represent clonally related disease or a second malignancy; and (2) is there a characteristic biologic

  5. Prevalence and clinical implications of epstein-barr virus infection in de novo diffuse large B-cell lymphoma in Western countries

    DEFF Research Database (Denmark)

    Ok, Chi Young; Li, Ling; Xu-Monette, Zijun Y

    2014-01-01

    PURPOSE: Epstein-Barr virus-positive (EBV(+)) diffuse large B-cell lymphoma (DLBCL) of the elderly is a variant of DLBCL with worse outcome that occurs most often in East-Asian countries and is uncommon in the Western hemisphere. We studied the largest cohort of EBV(+) DLBCL, independent of age...

  6. Concordant bone marrow involvement of diffuse large B-cell lymphoma represents a distinct clinical and biological entity in the era of immunotherapy

    DEFF Research Database (Denmark)

    Yao, Zhilei; Deng, Lijuan; Xu-Monette, Z Y

    2018-01-01

    In diffuse large B-cell lymphoma (DLBCL), the clinical and biological significance of concordant and discordant bone marrow (BM) involvement have not been well investigated. We evaluated 712 de novo DLBCL patients with front-line rituximab-containing treatment, including 263 patients with positiv...

  7. Sarcopenia is an independent prognostic factor in elderly patients with diffuse large B-cell lymphoma treated with immunochemotherapy.

    Science.gov (United States)

    Lanic, Hélène; Kraut-Tauzia, Jerôme; Modzelewski, Romain; Clatot, Florian; Mareschal, Sylvain; Picquenot, Jean Michel; Stamatoullas, Aspasia; Leprêtre, Stéphane; Tilly, Hervé; Jardin, Fabrice

    2014-04-01

    Approximately 25-35% of patients with diffuse large B-cell lymphoma (DLBCL) are older than 70 years. The aim of this study was to investigate the prognostic impact of depletion of skeletal muscle (sarcopenia) in elderly patients with DLBCL. This retrospective analysis included 82 patients with DLBCL older than 70 years and treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, Oncovin, prednisone) or R-miniCHOP. Sarcopenia was measured by the analysis of stored computed tomography (CT) images at the L3 level at baseline. The surface of the muscular tissues was selected according to the CT Hounsfield unit. This value was normalized for stature in order to calculate the lumbar L3 skeletal muscle index (LSMI, in cm(2)/m(2)). The mean age of the population was 78 years. According to the defined cut-offs for LSMI, 45 patients with DLBCL were considered sarcopenic. Sarcopenic patients displayed a higher revised International Prognostic Index (R-IPI) compared with patients without sarcopenia, and were older, with a mean age of 80 years and 77 years, respectively (p = 0.006). With a median follow-up of 39 months, the 2-year overall survival in the sarcopenic population was 46% compared with 84% in the non-sarcopenic group (HR = 3.22; 95% CI = 1.73-5.98; p = 0.0002). In a multivariate analysis, sarcopenia remained predictive of outcome (p = 0.005). Sarcopenia is a relevant and predictive factor in elderly patients with DLBCL treated with rituximab plus chemotherapy.

  8. Molecular Mechanisms of Disease Progression in Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type during Ibrutinib Therapy

    Directory of Open Access Journals (Sweden)

    Lucy C. Fox

    2018-06-01

    Full Text Available Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT is one of the well-recognized extranodal lymphomas commonly addicted to the B-cell receptor-MYD88 superpathway. We aimed to describe the genomic changes in a patient who progressed through treatment with ibrutinib, a Bruton’s tyrosine kinase (BTK inhibitor. An 80-year-old woman presented with multiply relapsed PCDLBCL-LT after multiple lines of chemoimmunotherapy and radiotherapy. Pre-treatment testing of the localized cutaneous tumor lesion on a lymphoid amplicon panel demonstrated an MYD88 p.L265P mutation. Ibrutinib therapy was subsequently commenced, resulting in complete resolution of the skin disease. Despite an ongoing skin response, the patient developed progressive nodal disease at two months. Genomic analysis of the cutaneous tumor sample at baseline was compared to that of the inguinal lymph node upon progression, and revealed the acquisition of multiple genomic changes. These included several aberrations expected to bypass BTK inhibition, including two CARD11-activating mutations, and a deleterious mutation in the nuclear factor kappa B (NF-κB negative regulator, NFKBIE. In addition, an IgH-IRF8 translocation was detected (which brings the IRF8 transcription factor under control of the immunoglobulin heavy chain locus, representing a third plausible mechanism contributing to ibrutinib resistance. Several copy-number changes occurred in both samples, including an amplification of 18q, which encodes the anti-apoptotic protein BCL2. We describe the first case of novel genomic changes of PCDLBCL-LT that occurred while on ibrutinib, providing important mechanistic insights into both pathogenesis and drug resistance.

  9. The prognosis of MYC translocation positive diffuse large B-cell lymphoma depends on the second hit.

    Science.gov (United States)

    Clipson, Alexandra; Barrans, Sharon; Zeng, Naiyan; Crouch, Simon; Grigoropoulos, Nicholas F; Liu, Hongxiang; Kocialkowski, Sylvia; Wang, Ming; Huang, Yuanxue; Worrillow, Lisa; Goodlad, John; Buxton, Jenny; Neat, Michael; Fields, Paul; Wilkins, Bridget; Grant, John W; Wright, Penny; Ei-Daly, Hesham; Follows, George A; Roman, Eve; Watkins, A James; Johnson, Peter W M; Jack, Andrew; Du, Ming-Qing

    2015-07-01

    A proportion of MYC translocation positive diffuse large B-cell lymphomas (DLBCL) harbour a BCL2 and/or BCL6 translocation, known as double-hit DLBCL, and are clinically aggressive. It is unknown whether there are other genetic abnormalities that cooperate with MYC translocation and form double-hit DLBCL, and whether there is a difference in clinical outcome between the double-hit DLBCL and those with an isolated MYC translocation. We investigated TP53 gene mutations along with BCL2 and BCL6 translocations in a total of 234 cases of DLBCL, including 81 with MYC translocation. TP53 mutations were investigated by PCR and sequencing, while BCL2 and BCL6 translocation was studied by interphase fluorescence in situ hybridization. The majority of MYC translocation positive DLBCLs (60/81 = 74%) had at least one additional genetic hit. In MYC translocation positive DLBCL treated by R-CHOP ( n  = 67), TP53 mutation and BCL2, but not BCL6 translocation had an adverse effect on patient overall survival. In comparison with DLBCL with an isolated MYC translocation, cases with MYC/TP53 double-hits had the worst overall survival, followed by those with MYC/BCL2 double-hits. In MYC translocation negative DLBCL treated by R-CHOP ( n  = 101), TP53 mutation, BCL2 and BCL6 translocation had no impact on patient survival. The prognosis of MYC translocation positive DLBCL critically depends on the second hit, with TP53 mutations and BCL2 translocation contributing to an adverse prognosis. It is pivotal to investigate both TP53 mutations and BCL2 translocations in MYC translocation positive DLBCL, and to distinguish double-hit DLBCLs from those with an isolated MYC translocation.

  10. Prognostic significance of immunohistochemistry-based markers and algorithms in immunochemotherapy-treated diffuse large B cell lymphoma patients.

    Science.gov (United States)

    Culpin, Rachel E; Sieniawski, Michal; Angus, Brian; Menon, Geetha K; Proctor, Stephen J; Milne, Paul; McCabe, Kate; Mainou-Fowler, Tryfonia

    2013-12-01

    To reassess the prognostic validity of immunohistochemical markers and algorithms identified in the CHOP era in immunochemotherapy-treated diffuse large B cell lymphoma patients. The prognostic significance of immunohistochemical markers (CD10, Bcl-6, Bcl-2, MUM1, Ki-67, CD5, GCET1, FoxP1, LMO2) and algorithms (Hans, Hans*, Muris, Choi, Choi*, Nyman, Visco-Young, Tally) was assessed using clinical diagnostic blocks taken from an unselected, population-based cohort of 190 patients treated with R-CHOP. Dichotomizing expression, low CD10 (<10%), low LMO2 (<70%) or high Bcl-2 (≥80%) predicted shorter overall survival (OS; P = 0.033, P = 0.010 and P = 0.008, respectively). High Bcl-2 (≥80%), low Bcl-6 (<60%), low GCET1 (<20%) or low LMO2 (<70%) predicted shorter progression-free survival (PFS; P = 0.001, P = 0.048, P = 0.045 and P = 0.002, respectively). The Hans, Hans* and Muris classifiers predicted OS (P = 0.022, P = 0.037 and P = 0.011) and PFS (P = 0.021, P = 0.020 and P = 0.004). The Choi, Choi* and Tally were associated with PFS (P = 0.049, P = 0.009 and P = 0.023). In multivariate analysis, the International Prognostic Index (IPI) was the only independent predictor of outcome (OS; HR: 2.60, P < 0.001 and PFS; HR: 2.91, P < 0.001). Results highlight the controversy surrounding immunohistochemistry-based algorithms in the R-CHOP era. The need for more robust markers, applicable to the clinic, for incorporation into improved prognostic systems is emphasized. © 2013 John Wiley & Sons Ltd.

  11. An inflammation-based cumulative prognostic score system in patients with diffuse large B cell lymphoma in rituximab era.

    Science.gov (United States)

    Sun, Feifei; Zhu, Jia; Lu, Suying; Zhen, Zijun; Wang, Juan; Huang, Junting; Ding, Zonghui; Zeng, Musheng; Sun, Xiaofei

    2018-01-02

    Systemic inflammatory parameters are associated with poor outcomes in malignant patients. Several inflammation-based cumulative prognostic score systems were established for various solid tumors. However, there is few inflammation based cumulative prognostic score system for patients with diffuse large B cell lymphoma (DLBCL). We retrospectively reviewed 564 adult DLBCL patients who had received rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) therapy between Nov 1 2006 and Dec 30 2013 and assessed the prognostic significance of six systemic inflammatory parameters evaluated in previous studies by univariate and multivariate analysis:C-reactive protein(CRP), albumin levels, the lymphocyte-monocyte ratio (LMR), the neutrophil-lymphocyte ratio(NLR), the platelet-lymphocyte ratio(PLR)and fibrinogen levels. Multivariate analysis identified CRP, albumin levels and the LMR are three independent prognostic parameters for overall survival (OS). Based on these three factors, we constructed a novel inflammation-based cumulative prognostic score (ICPS) system. Four risk groups were formed: group ICPS = 0, ICPS = 1, ICPS = 2 and ICPS = 3. Advanced multivariate analysis indicated that the ICPS model is a prognostic score system independent of International Prognostic Index (IPI) for both progression-free survival (PFS) (p systemic inflammatory status was associated with clinical outcomes of patients with DLBCL in rituximab era. The ICPS model was shown to classify risk groups more accurately than any single inflammatory prognostic parameters. These findings may be useful for identifying candidates for further inflammation-related mechanism research or novel anti-inflammation target therapies.

  12. A strategy for full interrogation of prognostic gene expression patterns: exploring the biology of diffuse large B cell lymphoma.

    Directory of Open Access Journals (Sweden)

    Lisa M Rimsza

    Full Text Available Gene expression profiling yields quantitative data on gene expression used to create prognostic models that accurately predict patient outcome in diffuse large B cell lymphoma (DLBCL. Often, data are analyzed with genes classified by whether they fall above or below the median expression level. We sought to determine whether examining multiple cut-points might be a more powerful technique to investigate the association of gene expression with outcome.We explored gene expression profiling data using variable cut-point analysis for 36 genes with reported prognostic value in DLBCL. We plotted two-group survival logrank test statistics against corresponding cut-points of the gene expression levels and smooth estimates of the hazard ratio of death versus gene expression levels. To facilitate comparisons we also standardized the expression of each of the genes by the fraction of patients that would be identified by any cut-point. A multiple comparison adjusted permutation p-value identified 3 different patterns of significance: 1 genes with significant cut-point points below the median, whose loss is associated with poor outcome (e.g. HLA-DR; 2 genes with significant cut-points above the median, whose over-expression is associated with poor outcome (e.g. CCND2; and 3 genes with significant cut-points on either side of the median, (e.g. extracellular molecules such as FN1.Variable cut-point analysis with permutation p-value calculation can be used to identify significant genes that would not otherwise be identified with median cut-points and may suggest biological patterns of gene effects.

  13. [Early diffuse hypertrophic osteitis recurrence. Unexpected and consternating development after a large évidement cavity. Apropos of 15 cases].

    Science.gov (United States)

    Fleury, P; Basset, J M; Candau, P; Bré, M; Despreaux, G; Fabre, A; Saliba, N

    1985-01-01

    The authors report 15 cases collected over a period of 13 years (1972 - 1984) of a particularly serious eventuality affecting certain evacuation cavities: Early recurrence of diffuse hypertrophic osteitis (E.R.D.H.O.). This is a rare complication, occurring in 1.5% of cases of chronic otitis. However, the fact of having operated upon 7 cases in 1984 alone, whilst during the previous 12 years, only 8 had been seen, raised the alarm. The classical pattern of this complication occurs in 3 stages, each involving surgical operation: at the outset, chronic otitis with cholesteatoma or osteitis, most often mixed, for which an "inadequate" surgical procedure is performed. then, after a variable period which may exceed 10 years, a very large evacuation cavity was created by the authors. finally, 3rd and final stage: within 6 months, this cavity filled progressively and, at operation, the authors discovered a cavity virtually completely filled with a "fantastic" "moist sugar" osteitis, requiring a new evacuation cavity, even larger than that created before. In all cases, a successful result was obtained within a varying period, sometimes accompanied by spectacular improvement in general condition. The most plausible etiopathogenic hypothesis advanced to attempt to explain this phenomenon is that of secondary infection by a varied microbial flora, including, on the one hand, aerobic organisms usually discovered in such cases (pseudomonas pyocyaneus, proteus mirabilis) and, secondly, this being of essential importance, "anaerobic" bacteria, the bacteriological diagnosis of which requires application of a strict protocol. The authors have taken three decisions following their bibliographic investigations.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. DNMT1 is associated with cell cycle and DNA replication gene sets in diffuse large B-cell lymphoma.

    Science.gov (United States)

    Loo, Suet Kee; Ab Hamid, Suzina Sheikh; Musa, Mustaffa; Wong, Kah Keng

    2018-01-01

    Dysregulation of DNA (cytosine-5)-methyltransferase 1 (DNMT1) is associated with the pathogenesis of various types of cancer. It has been previously shown that DNMT1 is frequently expressed in diffuse large B-cell lymphoma (DLBCL), however its functions remain to be elucidated in the disease. In this study, we gene expression profiled (GEP) shRNA targeting DNMT1(shDNMT1)-treated germinal center B-cell-like DLBCL (GCB-DLBCL)-derived cell line (i.e. HT) compared with non-silencing shRNA (control shRNA)-treated HT cells. Independent gene set enrichment analysis (GSEA) performed using GEPs of shRNA-treated HT cells and primary GCB-DLBCL cases derived from two publicly-available datasets (i.e. GSE10846 and GSE31312) produced three separate lists of enriched gene sets for each gene sets collection from Molecular Signatures Database (MSigDB). Subsequent Venn analysis identified 268, 145 and six consensus gene sets from analyzing gene sets in C2 collection (curated gene sets), C5 sub-collection [gene sets from gene ontology (GO) biological process ontology] and Hallmark collection, respectively to be enriched in positive correlation with DNMT1 expression profiles in shRNA-treated HT cells, GSE10846 and GSE31312 datasets [false discovery rate (FDR) 0.8) with DNMT1 expression and significantly downregulated (log fold-change <-1.35; p<0.05) following DNMT1 silencing in HT cells. These results suggest the involvement of DNMT1 in the activation of cell cycle and DNA replication in DLBCL cells. Copyright © 2017 Elsevier GmbH. All rights reserved.

  15. Oxidative stress and redox state-regulating enzymes have prognostic relevance in diffuse large B-cell lymphoma

    Directory of Open Access Journals (Sweden)

    Peroja Pekka

    2012-03-01

    Full Text Available Abstract Background Oxidative stress and redox-regulating enzymes may have roles both in lymphomagenesis and resistance to lymphoma therapy. Previous studies from the pre-rituximab era suggest that antioxidant enzyme expression is related to prognosis in diffuse large B-cell lymphoma (DLBCL, although these results cannot be extrapolated to patient populations undergoing modern treatment modalities. In this study we assessed expression of the oxidative stress markers 8-hydroxydeoxyguanosine (8-OHdG and nitrotyrosine and the antioxidant enzymes thioredoxin (Trx, manganese superoxide dismutase (MnSOD and glutamate-cysteine ligase (GCL via immunohistochemistry in 106 patients with DLBCL. All patients were treated with CHOP-like therapy combined with rituximab. Immunostaining results were correlated with progression-free survival, disease-specific survival and traditional prognostic factors of DLBCL. Results Strong 8-OHdG immunostaining intensity was associated with extranodal involvement (p = 0.00002, a high International Prognostic Index (p = 0.002 and strong Trx (p = 0.011 and GCL (p = 0.0003 expression. Strong Trx staining intensity was associated with poor progression-free survival (p = 0.046 and poor disease-specific survival (p = 0.015. Strong GCL immunostaining intensity predicted poor progression-free survival (p = 0.049. Patients with either strong Trx or strong nitrotyrosine expression showed significantly poorer progression-free survival (p = 0.003 and disease-specific survival (p = 0.031 compared with the other patients. Conclusions The redox state-regulating enzymes GCL and Trx are promising markers in the evaluation of DLBCL prognosis in the era of modern immunochemotherapy.

  16. Implications of infiltrating immune cells within bone marrow of patients with diffuse large B-cell lymphoma.

    Science.gov (United States)

    Jeong, Juhyeon; Oh, Eun Ji; Yang, Woo Ick; Kim, Soo Jeong; Yoon, Sun Och

    2017-06-01

    The implications of infiltrating immune cells, especially T cells and macrophages, in the bone marrow (BM) microenvironment of patients with diffuse large B-cell lymphoma (DLBCL) have rarely been studied. We aimed to investigate the significance of infiltrating immune cells in the BM microenvironment as a prognostic factor for DLBCL patients. Using the initial pretreatment BM biopsy obtained from 198 DLBCL patients, we semiquantitatively evaluated CD3+ T cells, CD8+ T cells, and CD163+ macrophages that infiltrate into the paratrabecular and interstitial areas of BM by immunohistochemistry and analyzed their clinicopathological and prognostic implications. Levels of infiltrating CD3+ T cells, CD8+ T cells, and CD163+ macrophages were significantly higher in BM with DLBCL involvement (BMI-positive group) than in that without DLBCL involvement (BMI-negative group). Infiltration of CD8+ T cells significantly increased in cases with advanced Ann Arbor stage, elevated lactate dehydrogenase level, extranodal site involvement ≥2 sites, higher Eastern Cooperative Oncology Group performance status, and higher International Prognostic Index (IPI) risk. High levels of CD3+ T cells were significantly associated with age ≤60, and high levels of CD163+ macrophages were associated with advanced Ann Arbor stage and higher IPI risk. High infiltration of CD8+ T cells was significantly related to inferior overall and recurrence-free survival rate, even in the BMI-negative group. High infiltration of CD8+ T cells within the pretreatment BM was related to poor prognosis, and might be a useful prognostic factor of DLBCL patients. Therefore, evaluation of CD8+ T cells is helpful for predicting prognosis in initial pretreatment BM biopsy of DLBCL patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Primary Breast Mucosa-Associated Lymphoid Tissue (MALT Lymphoma Transformation to Diffuse Large B-cell Lymphoma: A Case Report

    Directory of Open Access Journals (Sweden)

    Şerife Hülya Arslan

    2012-09-01

    Full Text Available Primary non-Hodgkin’s lymphoma (NHL of the breast constitutes 0.04%-0.53% of all malignancies and 2.2% of extra nodal lymphomas. In total, 7%-8% of all B-cell lymphomas are the mucosa-associated lymphoid tissue (MALT type, of which up to 50% of primary gastric MALT lymphoma. Herein we present a patient with breast MALT lymphoma that transformed to diffuse large B-cell lymphoma (DLBCL. A 69-year-old female presented with a mass on her left breast. Physical examination showed a 3 × 3-cm mass located 1 cm from the areola on the upper lateral quadrant of the breast at the 1 o’clock position, which was fixed and firm. Excisional biopsy was performed and pathologic examination of the specimen showed MALT lymphoma transformation to DLBCL. The patient was staged as II-EA. The rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP protocol was scheduled as treatment. Following 6 courses of R-CHOP, 2 additional courses of rituximab were administered. Positron emission tomography (PET-CT was done at the end of the treatment. PET showed that the patient was in complete remission. At the time this report was written, the patient was being followed-up at the outpatient clinic on a regular basis. Lymphoma of the breast is a rarity among malignant tumors of the breast. The most common type of lymphoma is DLBCL. Breast MALT lymphoma is extremely rare. Primary MALT lymphoma of the breast can transform from low grade to high grade and recurrence is possible; therefore, such patients should be monitored carefully for transformation.

  18. PD-L1 expression in EBV-negative diffuse large B-cell lymphoma: clinicopathologic features and prognostic implications.

    Science.gov (United States)

    Xing, Wei; Dresser, Karen; Zhang, Rui; Evens, Andrew M; Yu, Hongbo; Woda, Bruce A; Chen, Benjamin J

    2016-09-13

    Programmed cell death ligand 1 (PD-L1) is a cell surface glycoprotein that regulates the cellular immune response and serves as a targetable immune checkpoint molecule. PD-L1 is expressed on tumor cells and the immune microenvironment of several human malignancies, including a subset of aggressive lymphomas. We sought to investigate further the clinical and pathologic features of EBV-negative diffuse large B-cell lymphoma (DLBCL) cases that express PD-L1. Immunohistochemical staining using an anti-PD-L1 monoclonal antibody was performed on DLBCL cases from 86 patients. These patients received standard chemotherapy treatment and were followed for up to 175 months. Overall, 14 cases (16%) were considered positive for PD-L1 in tumor cells. In comparison with PD-L1 negative cases, PD-L1 positive cases had a higher rate of non-GCB type (71% vs. 30%, P=0.0060), and higher Ann Arbor stage (II-IV) (100% vs. 73%, P=0.0327). No significant differences were seen in the immunohistochemical expression of BCL2, MYC, or Ki67. Patients with tumors expressing PD-L1 demonstrated inferior overall survival (OS) upon long term follow up (P=0.0447). Both age/sex-adjusted and multivariate analyses identified PD-L1 as an independent predictor for OS (P=0.0101 and P=0.0424). There was no significant difference, however, in terms of remission rates after first treatment, relapse rates, and progression free survival between the groups. Identification of DLBCL cases that express PD-L1 may serve to select a subset of patients that could further benefit from targeted immunotherapy.

  19. Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing

    Science.gov (United States)

    Lohr, Jens G.; Stojanov, Petar; Lawrence, Michael S.; Auclair, Daniel; Chapuy, Bjoern; Sougnez, Carrie; Cruz-Gordillo, Peter; Knoechel, Birgit; Asmann, Yan W.; Slager, Susan L.; Novak, Anne J.; Dogan, Ahmet; Ansell, Stephen M.; Zou, Lihua; Gould, Joshua; Saksena, Gordon; Stransky, Nicolas; Rangel-Escareño, Claudia; Fernandez-Lopez, Juan Carlos; Hidalgo-Miranda, Alfredo; Melendez-Zajgla, Jorge; Hernández-Lemus, Enrique; Schwarz-Cruz y Celis, Angela; Imaz-Rosshandler, Ivan; Ojesina, Akinyemi I.; Jung, Joonil; Pedamallu, Chandra S.; Lander, Eric S.; Habermann, Thomas M.; Cerhan, James R.; Shipp, Margaret A.; Getz, Gad; Golub, Todd R.

    2012-01-01

    To gain insight into the genomic basis of diffuse large B-cell lymphoma (DLBCL), we performed massively parallel whole-exome sequencing of 55 primary tumor samples from patients with DLBCL and matched normal tissue. We identified recurrent mutations in genes that are well known to be functionally relevant in DLBCL, including MYD88, CARD11, EZH2, and CREBBP. We also identified somatic mutations in genes for which a functional role in DLBCL has not been previously suspected. These genes include MEF2B, MLL2, BTG1, GNA13, ACTB, P2RY8, PCLO, and TNFRSF14. Further, we show that BCL2 mutations commonly occur in patients with BCL2/IgH rearrangements as a result of somatic hypermutation normally occurring at the IgH locus. The BCL2 point mutations are primarily synonymous, and likely caused by activation-induced cytidine deaminase–mediated somatic hypermutation, as shown by comprehensive analysis of enrichment of mutations in WRCY target motifs. Those nonsynonymous mutations that are observed tend to be found outside of the functionally important BH domains of the protein, suggesting that strong negative selection against BCL2 loss-of-function mutations is at play. Last, by using an algorithm designed to identify likely functionally relevant but infrequent mutations, we identify KRAS, BRAF, and NOTCH1 as likely drivers of DLBCL pathogenesis in some patients. Our data provide an unbiased view of the landscape of mutations in DLBCL, and this in turn may point toward new therapeutic strategies for the disease. PMID:22343534

  20. Racial differences in treatment and survival in older patients with diffuse large B-cell lymphoma (DLBCL)

    International Nuclear Information System (INIS)

    Griffiths, Robert; Gleeson, Michelle; Knopf, Kevin; Danese, Mark

    2010-01-01

    Diffuse large B-cell lymphoma (DLBCL) comprises 31% of lymphomas in the United States. Although it is an aggressive type of lymphoma, 40% to 50% of patients are cured with treatment. The study objectives were to identify patient factors associated with treatment and survival in DLBCL. Using Surveillance, Epidemiology, and End Results (SEER) registry data linked to Medicare claims, we identified 7,048 patients diagnosed with DLBCL between January 1, 2001 and December 31, 2005. Patients were followed from diagnosis until the end of their claims history (maximum December 31, 2007) or death. Medicare claims were used to characterize the first infused chemo-immunotherapy (C-I therapy) regimen and to identify radiation. Multivariate analyses were performed to identify patient demographic, socioeconomic, and clinical factors associated with treatment and with survival. Outcomes variables in the survival analysis were all-cause mortality, non-Hodgkin's lymphoma (NHL) mortality, and other/unknown cause mortality. Overall, 84% (n = 5,887) received C-I therapy or radiation treatment during the observation period: both, 26%; C-I therapy alone, 53%; and radiation alone, 5%. Median age at diagnosis was 77 years, 54% were female, 88% were white, and 43% had Stage III or IV disease at diagnosis. The median time to first treatment was 42 days, and 92% of these patients had received their first treatment by day 180 following diagnosis. In multivariate analysis, the treatment rate was significantly lower among patients ≥ 80 years old, blacks versus whites, those living in a census tract with ≥ 12% poverty, and extra-nodal disease. Blacks had a lower treatment rate overall (Hazard Ratio [HR] 0.77; P < 0.001), and were less likely to receive treatment within 180 days of diagnosis (Odds Ratio [OR] 0.63; P = 0.002) than whites. In multivariate survival analysis, black race was associated with higher all-cause mortality (HR 1.24; P = 0.01) and other/unknown cause mortality (HR 1

  1. Prognostic value of defining the systemic tumor volume with FDG-PET in diffuse large b cell lymphoma

    International Nuclear Information System (INIS)

    Byun, Byung Hyun; Lim, Sang Moo; Cheon, Gi Jeong; Choi, Chang Woon; Kang, Hye Jin; Na, Im Il; Ryoo, Baek Yeol; Yang, Sung Hyun

    2007-01-01

    We measured the systemic tumor volume using FDG-PET in patients with diffuse large B cell lymphoma (DLBL). We also investigated its prognostic role, and compared it with that of other prognostic factors. FDG PET was performed in 38 newly diagnosed DLBL patients (20 men, 18 women, age 55.715.1 years) at pre-treatment of chemotherapy. Clinical staging of lymphoma was evaluated by Ann Arbor system. On each FDG PET scan, we acquired volume of interest (VOl) at the cut-off value of SUV=2.5 in every measurable tumor by the automatic edge detection software. According to the VOI, we measured the metabolic volume and mean SUV, and estimated volume-activity indexes (SUV Vol) as mean SUV times metabolic volume. And then, we calculated the summed metabolic volume (VOLsum) and summed SUV Vol (SUV Volsum) in every FDG PET scan. Maximum SUV of involved lesion (SUVmax) was also acquired on each FDG PET scan. Time to treatment failure (TTF) was compared among VOLsum (median), SUV Volsum (median), SUVmax (median), clinical stage, gender, age, LDH, and performance status-assigned response designations by Kaplan-Meier survival analysis. Initial stages of DLBL patients were stage I in 4, II in 14, III in 15, and IV in 4 by Ann Arbor system. Median follow up period was 15.5months, and estimated mean TTF was 22.3 months. Univariate analysis demonstrated that TTF is statistically significantly reduced in those with high VOLsum (>215.1cm2, p=0.004), high SUV Volsum (>1577.5, p=0.003), and increased LDH (p=0.036). TTF did not correlate with SUVmax (p=0.571), clinical stage (p=0.194), gender (p=0.549), and age (p=0.128), and performance status =2 (p=0.074). Multivariate analysis using VOLsum, SUV Volsum, LDH, and performance status demonstrated no statistically significant predictor of TTF (p>0.05). Systemic tumor volume measurement using FDG-PET is suggestive to be the significant prognostic factor in patients with DLBL

  2. Diagnostic and prognostic value of baseline FDG PET/CT skeletal textural features in diffuse large B cell lymphoma.

    Science.gov (United States)

    Aide, Nicolas; Talbot, Marjolaine; Fruchart, Christophe; Damaj, Gandhi; Lasnon, Charline

    2018-05-01

    Our purpose was to evaluate the diagnostic and prognostic value of skeletal textural features (TFs) on baseline FDG PET in diffuse large B cell lymphoma (DLBCL) patients. Eighty-two patients with DLBCL who underwent a bone marrow biopsy (BMB) and a PET scan between December 2008 and December 2015 were included. Two readers blinded to the BMB results visually assessed PET images for bone marrow involvement (BMI) in consensus, and a third observer drew a volume of interest (VOI) encompassing the axial skeleton and the pelvis, which was used to assess skeletal TFs. ROC analysis was used to determine the best TF able to diagnose BMI among four first-order, six second-order and 11 third-order metrics, which was then compared for diagnosis and prognosis in disease-free patients (BMB-/PET-) versus patients considered to have BMI (BMB+/PET-, BMB-/PET+, and BMB+/PET+). Twenty-two out of 82 patients (26.8%) had BMI: 13 BMB-/PET+, eight BMB+/PET+ and one BMB+/PET-. Among the nine BMB+ patients, one had discordant BMI identified by both visual and TF PET assessment. ROC analysis showed that SkewnessH, a first-order metric, was the best parameter for identifying BMI with sensitivity and specificity of 81.8% and 81.7%, respectively. SkewnessH demonstrated better discriminative power over BMB and PET visual analysis for patient stratification: hazard ratios (HR), 3.78 (P = 0.02) versus 2.81 (P = 0.06) for overall survival (OS) and HR, 3.17 (P = 0.03) versus 1.26 (P = 0.70) for progression-free survival (PFS). In multivariate analysis accounting for IPI score, bulky status, haemoglobin and SkewnessH, the only independent predictor of OS was the IPI score, while the only independent predictor of PFS was SkewnessH. The better discriminative power of skeletal heterogeneity for risk stratification compared to BMB and PET visual analysis in the overall population, and more specifically in BMB-/PET- patients, suggests that it can be useful to identify diagnostically

  3. Ran GTPase-activating protein 1 is a therapeutic target in diffuse large B-cell lymphoma.

    Directory of Open Access Journals (Sweden)

    Kung-Chao Chang

    Full Text Available Lymphoma-specific biomarkers contribute to therapeutic strategies and the study of tumorigenesis. Diffuse large B-cell lymphoma (DLBCL is the most common type of malignant lymphoma. However, only 50% of patients experience long-term survival after current treatment; therefore, developing novel therapeutic strategies is warranted. Comparative proteomic analysis of two DLBCL lines with a B-lymphoblastoid cell line (LCL showed differential expression of Ran GTPase-activating protein 1 (RanGAP1 between them, which was confirmed using immunoblotting. Immunostaining showed that the majority of DLBCLs (92%, 46/50 were RanGAP1(+, while reactive lymphoid hyperplasia (n = 12 was RanGAP1(+ predominantly in germinal centers. RanGAP1 was also highly expressed in other B-cell lymphomas (BCL, n = 180 with brisk mitotic activity (B-lymphoblastic lymphoma/leukemia: 93%, and Burkitt lymphoma: 95% or cell-cycle dysregulation (mantle cell lymphoma: 83%, and Hodgkin's lymphoma 91%. Interestingly, serum RanGAP1 level was higher in patients with high-grade BCL (1.71 ± 2.28 ng/mL, n = 62 than in low-grade BCL (0.75 ± 2.12 ng/mL, n = 52 and healthy controls (0.55 ± 1.58 ng/mL, n = 75 (high-grade BCL vs. low-grade BCL, p = 0.002; high-grade BCL vs. control, p < 0.001, Mann-Whitney U test. In vitro, RNA interference of RanGAP1 showed no effect on LCL but enhanced DLBCL cell death (41% vs. 60%; p = 0.035 and cell-cycle arrest (G0/G1: 39% vs. 49%, G2/M: 19.0% vs. 7.5%; p = 0.030 along with decreased expression of TPX2 and Aurora kinases, the central regulators of mitotic cell division. Furthermore, ON 01910.Na (Estybon, a multikinase inhibitor induced cell death, mitotic cell arrest, and hyperphosphorylation of RanGAP1 in DLBCL cell lines but no effects in normal B and T cells. Therefore, RanGAP1 is a promising marker and therapeutic target for aggressive B-cell lymphoma, especially DLBCL.

  4. Coexistence of chronic myeloid leukemia and diffuse large B-cell lymphoma with antecedent chronic lymphocytic leukemia: a case report and review of the literature.

    Science.gov (United States)

    Abuelgasim, Khadega A; Rehan, Hinna; Alsubaie, Maha; Al Atwi, Nasser; Al Balwi, Mohammed; Alshieban, Saeed; Almughairi, Areej

    2018-03-11

    Chronic lymphocytic leukemia and chronic myeloid leukemia are the most common types of adult leukemia. However, it is rare for the same patient to suffer from both. Richter's transformation to diffuse large B-cell lymphoma is frequently observed in chronic lymphocytic leukemia. Purine analog therapy and the presence of trisomy 12, and CCND1 gene rearrangement have been linked to increased risk of Richter's transformation. The coexistence of chronic myeloid leukemia and diffuse large B-cell lymphoma in the same patient is extremely rare, with only nine reported cases. Here, we describe the first reported case of concurrent chronic myeloid leukemia and diffuse large B-cell lymphoma in a background of chronic lymphocytic leukemia. A 60-year-old Saudi man known to have diabetes, hypertension, and chronic active hepatitis B was diagnosed as having Rai stage II chronic lymphocytic leukemia, with trisomy 12 and rearrangement of the CCND1 gene in December 2012. He required no therapy until January 2016 when he developed significant anemia, thrombocytopenia, and constitutional symptoms. He received six cycles of fludarabine, cyclophosphamide, and rituximab, after which he achieved complete remission. One month later, he presented with progressive leukocytosis (mostly neutrophilia) and splenomegaly. Fluorescence in situ hybridization from bone marrow aspirate was positive for translocation (9;22) and reverse transcription polymerase chain reaction detected BCR-ABL fusion gene consistent with chronic myeloid leukemia. He had no morphologic or immunophenotypic evidence of chronic lymphocytic leukemia at the time. Imatinib, a first-line tyrosine kinase inhibitor, was started. Eight months later, a screening imaging revealed new liver lesions, which were confirmed to be diffuse large B-cell lymphoma. In chronic lymphocytic leukemia, progressive leukocytosis and splenomegaly caused by emerging chronic myeloid leukemia can be easily overlooked. It is unlikely that chronic myeloid

  5. Sulphate leaching from diffuse agricultural and forest sources in a large central European catchment during 1900-2010

    Czech Academy of Sciences Publication Activity Database

    Kopáček, Jiří; Hejzlar, Josef; Porcal, Petr; Posch, M.

    470, February (2014), s. 543-550 ISSN 0048-9697 R&D Projects: GA ČR(CZ) GAP504/12/1218; GA ČR(CZ) GA526/09/0567 Institutional support: RVO:60077344 Keywords : modelling * sulphate leaching * sulphur mineralization * diffuse sources Subject RIV: DJ - Water Pollution ; Quality Impact factor: 4.099, year: 2014

  6. CD7 Positive Diffuse Large B-Cell Lymphoma Arising in a Background of Follicular Lymphoma: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Elham Vali Betts

    2016-01-01

    Full Text Available Diffuse large B-cell lymphoma (DLBCL is a neoplasm of large B-lymphocytes with a diffuse growth pattern. The neoplastic cells express B-cell markers such as CD20 and PAX-5 and there may be coexpression of BCL-2, BCL-6, CD10, and MUM-1. With the exception of CD5, other T-cell markers are not commonly expressed in this neoplasm. Here, we describe the first reported case of a DLBCL with abnormal expression CD7 arising in a background of follicular lymphoma in an 81-year-old male who presented with a nontender left axillary mass. Additionally, no other T-cell antigens were expressed in this B-cell lymphoma. Expression of CD7 in DLBCL is exceptionally rare and its prognostic significance is unknown. Here, we describe this rare case with review of literature of known DLBCLs with expression of T-cell antigens.

  7. NASA/DOD Aerospace Knowledge Diffusion Research Project. Paper 62: The Influence of Knowledge Diffusion on Aeronautics Innovation: The Research, Development, and Production of Large Commercial Aircraft in France, Germany, and the United Kingdom

    Science.gov (United States)

    Golich, Vicki L.; Pinelli, Thomas E.

    1997-01-01

    This paper focuses on how European public policies-individually and collectively - influence the diffusion of knowledge and technology. It begins with an overview of the roles played historically and currently by European governments in the Research, Development and Production (RD&P) of Large Commercial Aircraft (LCA). The analytical framework brings together literature from global political economy, comparative politics, business management, and science and technology policy studies. It distinguishes between the production of knowledge, on the one hand, and the dissemination of knowledge, on the other. France, Germany, and the United Kingdom serve as the analytical cases. The paper concludes with a call for additional research in this area, some tentative lessons learned, and a discussion of the consequences of national strategies and policies for the diffusion of knowledge and technology in an era of globalizaton.

  8. Double-hit lymphomas constitute a highly aggressive subgroup in diffuse large B-cell lymphomas in the era of rituximab.

    Science.gov (United States)

    Kobayashi, Tsutomu; Tsutsumi, Yasuhiko; Sakamoto, Natsumi; Nagoshi, Hisao; Yamamoto-Sugitani, Mio; Shimura, Yuji; Mizutani, Shinsuke; Matsumoto, Yosuke; Nishida, Kazuhiro; Horiike, Shigeo; Asano, Naoko; Nakamura, Shigeo; Kuroda, Junya; Taniwaki, Masafumi

    2012-11-01

    The incorporation of rituximab in immunochemotherapy has improved treatment outcomes for diffuse large B-cell lymphoma, but the prognosis for some diffuse large B-cell lymphomas remains dismal. Identification of adverse prognostic subgroups is essential for the choice of appropriate therapeutic strategy. We retrospectively investigated the impact of so-called 'double-hit' cytogenetic abnormalities, i.e. cytogenetic abnormalities involving c-MYC co-existing with other poor prognostic cytogenetic abnormalities involving BCL2, BCL6 or BACH2, on treatment outcomes for 93 consecutive diffuse large B-cell lymphoma patients. According to the revised international prognostic index, no patients were cytogenetically diagnosed with double-hit lymphomas in the 'very good' risk group or in the 'good' risk group, while 5 of 33 patients had double-hit lymphomas in the 'poor' risk group. All the double-hit lymphoma patients possessed both nodal and extranodal involvement. The overall complete response rate was 89.3%, overall survival 87.1% and progression-free survival 75.8% over 2 years (median observation period: 644 days). The complete response rates were 93.2% for the non-double-hit lymphoma patients and 40.0% for the double-hit lymphoma patients. Significantly longer progression-free survival and overall survival were observed for the 'very good' and the 'good' risk patients than for the 'poor' risk patients. Moreover, the progression-free survival of double-hit lymphoma was significantly shorter than that of the non-double-hit lymphoma 'poor' risk patients (P = 0.016). In addition, the overall survival of the double-hit lymphoma patients also tended to be shorter than that of the non-double-hit lymphoma 'poor' risk group. The diagnosis of double-hit lymphoma can help discriminate a subgroup of highly aggressive diffuse large B-cell lymphomas and indicate the need for the development of novel therapeutic strategies for double-hit lymphoma.

  9. High microvessel density determines a poor outcome in patients with diffuse large B-cell lymphoma treated with rituximab plus chemotherapy

    Science.gov (United States)

    Cardesa-Salzmann, Teresa M.; Colomo, Luis; Gutierrez, Gonzalo; Chan, Wing C.; Weisenburger, Dennis; Climent, Fina; González-Barca, Eva; Mercadal, Santiago; Arenillas, Leonor; Serrano, Sergio; Tubbs, Ray; Delabie, Jan; Gascoyne, Randy D.; Connors, Joseph M; Mate, Jose L.; Rimsza, Lisa; Braziel, Rita; Rosenwald, Andreas; Lenz, Georg; Wright, George; Jaffe, Elaine S.; Staudt, Louis; Jares, Pedro; López-Guillermo, Armando; Campo, Elias

    2011-01-01

    Background Diffuse large B-cell lymphoma is a clinically and molecularly heterogeneous disease. Gene expression profiling studies have shown that the tumor microenvironment affects survival and that the angiogenesis-related signature is prognostically unfavorable. The contribution of histopathological microvessel density to survival in diffuse large B-cell lymphomas treated with immunochemotherapy remains unknown. The purpose of this study is to assess the prognostic impact of histopathological microvessel density in two independent series of patients with diffuse large B-cell lymphoma treated with immunochemotherapy. Design and Methods One hundred and forty-seven patients from the Leukemia Lymphoma Molecular Profiling Project (training series) and 118 patients from the Catalan Lymphoma-Study group-GELCAB (validation cohort) were included in the study. Microvessels were immunostained with CD31 and quantified with a computerized image analysis system. The stromal scores previously defined in 110 Leukemia Lymphoma Molecular Profiling Project cases were used to analyze correlations with microvessel density data. Results Microvessel density significantly correlated with the stromal score (r=0.3209; P<0.001). Patients with high microvessel density showed significantly poorer overall survival than those with low microvessel density both in the training series (4-year OS 54% vs. 78%; P=0.004) and in the validation cohort (57% vs. 81%; P=0.006). In multivariate analysis, in both groups high microvessel density was a statistically significant unfavorable prognostic factor independent of international prognostic index [training series: international prognostic index (relative risk 2.7; P=0.003); microvessel density (relative risk 1.96; P=0.002); validation cohort: international prognostic index (relative risk 4.74; P<0.001); microvessel density (relative risk 2.4; P=0.016)]. Conclusions These findings highlight the impact of angiogenesis in the outcome of patients with

  10. CD30 expression defines a novel subgroup of diffuse large B-cell lymphoma with favorable prognosis and distinct gene expression signature

    DEFF Research Database (Denmark)

    Hu, Shimin; Xu-Monette, Zijun Y; Balasubramanyam, Aarthi

    2013-01-01

    CD30, originally identified as a cell-surface marker of Reed-Sternberg and Hodgkin cells of classical Hodgkin lymphoma, is also expressed by several types of non-Hodgkin lymphoma, including a subset of diffuse large B-cell lymphoma (DLBCL). However, the prognostic and biological importance of CD3...... value of CD30 as a therapeutic target for brentuximab vedotin in ongoing successful clinical trials, it seems appropriate to consider CD30(+) DLBCL as a distinct subgroup of DLBCL....

  11. B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Burkitt's lymphoma: A case report and review

    OpenAIRE

    Chettiankandy, Tabita Joy; Tupkari, Jagdish Vishnu; Kumar, Keshav; Ahire, Manisha Sandeep

    2016-01-01

    B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma (DLBCL) and classical Burkitt's lymphoma (BL), is a diagnostic provisional category in the World Health Organization 2008 classification of lymphomas. This category was designed as a measure to accommodate borderline cases that cannot be reliably classified into a single distinct disease entity after all available morphological, immunophenotypical and molecular studies have been performed. Typica...

  12. Vav-1 expression correlates with NFkappaB activation and CD40-mediated cell death in diffuse large B-cell lymphoma cell lines

    DEFF Research Database (Denmark)

    Hollmann, Annette; Aloyz, Raquel; Baker, Kristi

    2010-01-01

    Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy with a variable response to therapy. We have previously shown that DLBCL cell lines differ in their susceptibility to CD40-mediated cell death, and that resistance to CD40-targeted antibodies correlated with increased expression...... as a potential marker to identify tumours likely to respond to CD40-targeted therapies. Copyright (c) 2010 John Wiley & Sons, Ltd....

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

    Science.gov (United States)

    Valera, Alexandra; López-Guillermo, Armando; Cardesa-Salzmann, Teresa; 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; Martínez, Daniel; Castillo, Paola; Rovira, Jordina; Martínez, Antonio; Campo, Elias; Colomo, Luis

    2013-10-01

    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 rearrangements (MYC double/triple-hit) in 4%, MYC amplifications in 2% and MYC gains in 19%. MYC single-hit, MYC double/triple-hit and MYC amplifications, but not MYC gains or other gene rearrangements, were associated with unfavorable progression-free survival and overall survival. MYC protein expression, evaluated using computerized image analysis, captured the unfavorable prognosis of MYC translocations/amplifications and identified an additional subset of patients without gene alterations but with similar poor prognosis. Patients with tumors expressing both MYC/BCL2 had the worst prognosis, whereas those with double-negative tumors had the best outcome. High MYC expression was associated with shorter overall survival irrespectively of the International Prognostic Index and BCL2 expression. In conclusion, MYC protein expression identifies a subset of diffuse large B-cell lymphoma with very poor prognosis independently of gene alterations and other prognostic parameters.

  14. Primary diffuse large B-cell lymphoma of the oral cavity Linfoma difuso de grandes células B primário de boca

    Directory of Open Access Journals (Sweden)

    Bruno Correia Jham

    2007-10-01

    Full Text Available Lymphomas arising within the oral cavity account for only 3.5% of all oral malignancies. Diffuse large B-cell lymphoma is a non-Hodgkin lymphoma subtype characterized by diffuse proliferation of large neoplastic B lymphoid cells. This paper reports a case of diffuse large B-cell lymphoma affecting the oral cavity of a Brazilian woman, along with its clinical, microscopical, immunohistochemical, and molecular features.Linfomas correspondem a 3,5% de todos os casos de lesões malignas de boca. O linfoma difuso de grandes células B é um subtipo de linfoma não-Hodgkin caracterizado pela proliferação difusa de células linfóides B. Este artigo relata um caso de linfoma difuso de grandes células B localizado na cavidade bucal de uma mulher brasileira, incluindo os achados clínicos, microscópicos, imuno-histoquímicos e moleculares.

  15. Measurements of beam halo diffusion and population density in the Tevatron and in the Large Hadron Collider

    CERN Document Server

    Stancari, Giulio

    Halo dynamics influences global accelerator performance: beam lifetimes, emittance growth, dynamic aperture, and collimation efficiency. Halo monitoring and control are also critical for the operation of high-power machines. For instance, in the high-luminosity upgrade of the LHC, the energy stored in the beam tails may reach several megajoules. Fast losses can result in superconducting magnet quenches, magnet damage, or even collimator deformation. The need arises to measure the beam halo and to remove it at controllable rates. In the Tevatron and in the LHC, halo population densities and diffusivities were measured with collimator scans by observing the time evolution of losses following small inward or outward collimator steps, under different experimental conditions: with single beams and in collision, and, in the case of the Tevatron, with a hollow electron lens acting on a subset of bunches. After the LHC resumes operations, it is planned to compare measured diffusivities with the known strength of tran...

  16. On the group approximation errors in description of neutron slowing-down at large distances from a source. Diffusion approach

    International Nuclear Information System (INIS)

    Kulakovskij, M.Ya.; Savitskij, V.I.

    1981-01-01

    The errors of multigroup calculating the neutron flux spatial and energy distribution in the fast reactor shield caused by using group and age approximations are considered. It is shown that at small distances from a source the age theory rather well describes the distribution of the slowing-down density. With the distance increase the age approximation leads to underestimating the neutron fluxes, and the error quickly increases at that. At small distances from the source (up to 15 lengths of free path in graphite) the multigroup diffusion approximation describes the distribution of slowing down density quite satisfactorily and at that the results almost do not depend on the number of groups. With the distance increase the multigroup diffusion calculations lead to considerable overestimating of the slowing-down density. The conclusion is drawn that the group approximation proper errors are opposite in sign to the error introduced by the age approximation and to some extent compensate each other

  17. Fully implicit solution of large-scale non-equilibrium radiation diffusion with high order time integration

    International Nuclear Information System (INIS)

    Brown, Peter N.; Shumaker, Dana E.; Woodward, Carol S.

    2005-01-01

    We present a solution method for fully implicit radiation diffusion problems discretized on meshes having millions of spatial zones. This solution method makes use of high order in time integration techniques, inexact Newton-Krylov nonlinear solvers, and multigrid preconditioners. We explore the advantages and disadvantages of high order time integration methods for the fully implicit formulation on both two- and three-dimensional problems with tabulated opacities and highly nonlinear fusion source terms

  18. Numerical simulation of nonstationary dissipative structures in 3D double-diffusive convection at large Rayleigh numbers

    Science.gov (United States)

    Kozitskiy, Sergey

    2018-05-01

    Numerical simulation of nonstationary dissipative structures in 3D double-diffusive convection has been performed by using the previously derived system of complex Ginzburg-Landau type amplitude equations, valid in a neighborhood of Hopf bifurcation points. Simulation has shown that the state of spatiotemporal chaos develops in the system. It has the form of nonstationary structures that depend on the parameters of the system. The shape of structures does not depend on the initial conditions, and a limited number of spectral components participate in their formation.

  19. Measurements of beam halo diffusion and population density in the Tevatron and in the Large Hadron Collider

    Energy Technology Data Exchange (ETDEWEB)

    Stancari, Giulio [Fermilab

    2015-03-01

    Halo dynamics influences global accelerator performance: beam lifetimes, emittance growth, dynamic aperture, and collimation efficiency. Halo monitoring and control are also critical for the operation of high-power machines. For instance, in the high-luminosity upgrade of the LHC, the energy stored in the beam tails may reach several megajoules. Fast losses can result in superconducting magnet quenches, magnet damage, or even collimator deformation. The need arises to measure the beam halo and to remove it at controllable rates. In the Tevatron and in the LHC, halo population densities and diffusivities were measured with collimator scans by observing the time evolution of losses following small inward or outward collimator steps, under different experimental conditions: with single beams and in collision, and, in the case of the Tevatron, with a hollow electron lens acting on a subset of bunches. After the LHC resumes operations, it is planned to compare measured diffusivities with the known strength of transverse damper excitations. New proposals for nondestructive halo population density measurements are also briefly discussed.

  20. Ascites as the initial characteristic manifestation in a patient with primary gastric CD8-positive diffuse large B-cell lymphoma.

    Science.gov (United States)

    Zhao, K-X; Dai, G-Z; Zhu, J-F

    2016-05-01

    Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy and the most common type of non-Hodgkin's lymphomas, the stomach is the most common extranodal site. Gastric DLBCL is often characterized by epigastric pain and vomiting. We report a case of a 78-year-old female patient with gastric diffuse large B-cell lymphoma (DLBCL) with high CD8 level which was initially manifested with ascites of unknown origin. The patient was admitted with a chief complaint of abdominal distension and scanty urine over the last twenty days, while without anorexia and fatigue until 15 March. She had no history of viral hepatitis, tuberculosis, schistosomiasis. Laboratory data revealed normal aminotransferases and bilirubin levels, but serum lactate dehydrogenase, CA125, ascitic fluid lactate dehydrogenase, ascitic fluid lymphocytes increased. The ascitic fluid was yellow-colored with 98.5% lymphocytes. Stool occult blood test was positive. Upper gastrointestinal endoscopy performed a few days later revealed multiple gastric crateriform ulcers, and Helicobacter pylori was detected in the biopsy specimen. Peripheral blood CD8+ was increased by 51%. Pathology test showed lymphocytes with atypical hyperplasia, and immunohistochemistry test resulted CD20+, CD10-, CD79α+, κ+, bcl-6+, Ki-67+ (approximately 95%), λ-, bcl-2-, CD3-, CD43-. Immunoglobulin gene (Ig) clonal rearrangement showed IgH: FR1 (+), FR2 (+), FR3(-), Igk: VJ(+), Vkde (+) in lymphoma tissue. The features of histopathology and immunohistochemistry of the tissue confirmed diffuse large B-cell lymphoma (DLBL). The patient received an uncompleted CHOP program combined with H. pylori eradication. However, the patient deceased due to disease development sixteen days later after the diagnosis.

  1. Reduction of ion thermal diffusivity associated with the transition of the radial electric field in neutral-beam-heated plasmas in the large helical device.

    Science.gov (United States)

    Ida, K; Funaba, H; Kado, S; Narihara, K; Tanaka, K; Takeiri, Y; Nakamura, Y; Ohyabu, N; Yamazaki, K; Yokoyama, M; Murakami, S; Ashikawa, N; deVries, P C; Emoto, M; Goto, M; Idei, H; Ikeda, K; Inagaki, S; Inoue, N; Isobe, M; Itoh, K; Kaneko, O; Kawahata, K; Khlopenkov, K; Komori, A; Kubo, S; Kumazawa, R; Liang, Y; Masuzaki, S; Minami, T; Miyazawa, J; Morisaki, T; Morita, S; Mutoh, T; Muto, S; Nagayama, Y; Nakanishi, H; Nishimura, K; Noda, N; Notake, T; Kobuchi, T; Ohdachi, S; Ohkubo, K; Oka, Y; Osakabe, M; Ozaki, T; Pavlichenko, R O; Peterson, B J; Sagara, A; Saito, K; Sakakibara, S; Sakamoto, R; Sanuki, H; Sasao, H; Sasao, M; Sato, K; Sato, M; Seki, T; Shimozuma, T; Shoji, M; Suzuki, H; Sudo, S; Tamura, N; Toi, K; Tokuzawa, T; Torii, Y; Tsumori, K; Yamamoto, T; Yamada, H; Yamada, I; Yamaguchi, S; Yamamoto, S; Yoshimura, Y; Watanabe, K Y; Watari, T; Hamada, Y; Motojima, O; Fujiwara, M

    2001-06-04

    Recent large helical device experiments revealed that the transition from ion root to electron root occurred for the first time in neutral-beam-heated discharges, where no nonthermal electrons exist. The measured values of the radial electric field were found to be in qualitative agreement with those estimated by neoclassical theory. A clear reduction of ion thermal diffusivity was observed after the mode transition from ion root to electron root as predicted by neoclassical theory when the neoclassical ion loss is more dominant than the anomalous ion loss.

  2. Minimal Loss of Lifetime for Patients With Diffuse Large B-Cell Lymphoma in Remission and Event Free 24 Months After Treatment

    DEFF Research Database (Denmark)

    Jakobsen, Lasse Hjort; Bøgsted, Martin; Brown, Peter de Nully

    2017-01-01

    Purpose The general outlook for patients with diffuse large B-cell lymphoma (DLBCL) in first remission is important information for patients and for planning post-treatment follow-up. The purpose of this study was to evaluate the survival of patients with DLBCL in remission compared with a matched......). During the first 8 years after pEFS24, the average loss of lifetime was 0.31 mo/y (95% CI, 0.11 to 0.50 mo/y). Excess mortality diminished when analyzing death from lymphoma as competing event to death from other causes, suggesting that early and late relapse is responsible for increased mortality...

  3. An International Collaborative Study of Outcome and Prognostic Factors in Patients with Secondary CNS Involvement By Diffuse Large B-Cell Lymphoma

    DEFF Research Database (Denmark)

    El-Galaly, Tarec Christoffer; Cheah, Chan Yoon; Bendtsen, Mette Dahl

    2016-01-01

    ) determine prognostic factors after SCNS.Patients and methods: We performed a retrospective study of patients diagnosed with SCNS during or after frontline immunochemotherapy (R-CHOP or equivalently effective regimens). SCNS was defined as new involvement of the CNS (parenchymal, leptomeningeal, and/or eye......Background: Secondary CNS involvement (SCNS) is a detrimental complication seen in ~5% of patients with diffuse large B-cell lymphoma (DLBCL) treated with modern immunochemotherapy. Data from older series report short survival following SCNS, typically lt;6 months. However, data in patients...

  4. Somatic mutation of EZH2 (Y641) in follicular and diffuse large B-cell lymphomas of germinal center origin | Office of Cancer Genomics

    Science.gov (United States)

    Morin et al. describe recurrent somatic mutations in EZH2, a polycomb group oncogene. The mutation, found in the SET domain of this gene encoding a histone methyltransferase, is found only in a subset of lymphoma samples. Specifically, EZH2 mutations are found in about 12% of follicular lymphomas (FL) and almost 23% of diffuse large B-cell lymphomas (DLBCL) of germinal center origin. This paper goes on to demonstrate that altered EZH2 proteins, corresponding to the most frequent mutations found in human lymphomas, have reduced activity using in vitro histone methylation assays.

  5. Indoor NO/sub 2/ sampling in a large university campus in Benin city, southern Nigeria, using flames diffusion tubes

    International Nuclear Information System (INIS)

    Ukpebor, E.E.; Sadiku, Y.T.; Ahonkhai, S.I.

    2005-01-01

    Monitoring of NO/sub 2/ in different indoor environments (without cooking and with cooking using different fuels) was done. Flames diffusion tubes were used for the monitoring. The sampling duration was two weeks. The highest NO/sub 2/ concentration of 38.61 ppb (73.74 mug/m3) was monitored in the room where the cooking was done with a gas burner. This was followed by the room with firewood cooking, where the concentration was 36.75 ppb (70.19 mug/m3) and the least concentration of 24.05 ppb (46.80 mug/m3) was noted in the room, where kerosene stove was used for cooking. It is of significance to observe that the WHO annual average guideline value of 40 mug/m3 was exceeded in al the rooms where cooking was done. Levels obtained in this study, therefore, suggest a need for precautionary mitigation. However, the outdoor concentration of NO/sub 2/ was almost the same as that obtained indoors in the rooms without cooking. This suggests high penetration indoors of outdoor NO/sub 2/. A background level of 3.40 ppb (6.49 mug/m3) was established for the environment in Ugbowo, Benin City, Nigeria. (author)

  6. Excellent outcome of immunomodulation or Bruton’s tyrosine kinase inhibition in highly refractory primary cutaneous diffuse large B-cell lymphoma, leg type

    Directory of Open Access Journals (Sweden)

    Eva Gupta

    2015-12-01

    Full Text Available Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT is a rare diffuse large B-cell lymphoma confined to the skin of the legs. The typical presentation is characterized by solitary or multiple growing plaques, usually confined to one leg. We report a case of PCDLBCL-LT of activated B-cell subtype characterized by multiple local relapses in the legs, initially, and systemic relapses about seven years after the diagnosis. Local relapses were sensitive to radiation therapy. Cutaneous and systemic relapses responded well to immunomodulatory therapy with lenalidomide followed by Bruton’s tyrosine kinase inhibition with ibrutinib. Ibrutinib is the only treatment that resulted in long-lasting complete remission. Lenalidomide and especially ibrutinib appear to have a significant activity against this lymphoma and should be incorporated in the treatment of this resistant and aggressive lymphoma. To our knowledge, this is the first case of PCDLBCL-LT reported in the literature exhibiting a complete response to ibrutinib.

  7. Resveratrol suppresses constitutive activation of AKT via generation of ROS and induces apoptosis in diffuse large B cell lymphoma cell lines.

    Directory of Open Access Journals (Sweden)

    Azhar R Hussain

    Full Text Available BACKGROUND: We have recently shown that deregulation PI3-kinase/AKT survival pathway plays an important role in pathogenesis of diffuse large B cell lymphoma (DLBCL. In an attempt to identify newer therapeutic agents, we investigated the role of Resveratrol (trans-3,4', 5-trihydroxystilbene, a naturally occurring polyphenolic compound on a panel of diffuse large B-cell lymphoma (DLBCL cells in causing inhibition of cell viability and inducing apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the action of Resveratrol on DLBCL cells and found that Resveratrol inhibited cell viability and induced apoptosis by inhibition of constitutively activated AKT and its downstream targets via generation of reactive oxygen species (ROS. Simultaneously, Resveratrol treatment of DLBCL cell lines also caused ROS dependent upregulation of DR5; and interestingly, co-treatment of DLBCL with sub-toxic doses of TRAIL and Resveratrol synergistically induced apoptosis via utilizing DR5, on the other hand, gene silencing of DR5 abolished this effect. CONCLUSION/SIGNIFICANCE: Altogether, these data suggest that Resveratrol acts as a suppressor of AKT/PKB pathway leading to apoptosis via generation of ROS and at the same time primes DLBCL cells via up-regulation of DR5 to TRAIL-mediated apoptosis. These data raise the possibility that Resveratrol may have a future therapeutic role in DLBCL and possibly other malignancies with constitutive activation of the AKT/PKB pathway.

  8. STAT3 activation is associated with cerebrospinal fluid interleukin-10 (IL-10) in primary central nervous system diffuse large B cell lymphoma.

    Science.gov (United States)

    Mizowaki, Takashi; Sasayama, Takashi; Tanaka, Kazuhiro; Mizukawa, Katsu; Takata, Kumi; Nakamizo, Satoshi; Tanaka, Hirotomo; Nagashima, Hiroaki; Nishihara, Masamitsu; Hirose, Takanori; Itoh, Tomoo; Kohmura, Eiji

    2015-09-01

    Signal transducers and activators of transcription 3 (STAT3) are activated by various cytokines and oncogenes; however, the activity and pathogenesis of STAT3 in diffuse large B cell lymphoma of the central nervous system have not been thoroughly elucidated. We investigated the phosphorylation levels of STAT3 in 40 specimens of primary central nervous system diffuse large B-cell lymphoma (PCNS DLBCL) and analyzed the association between phsopho-STAT3 (pSTAT3) expression and cerebrospinal fluid (CSF) concentration of interleukin-10 (IL-10) or IL-6. Immunohistochemistry and Western blot analysis revealed that most of the specimens in PCNS DLBCL expressed pSTST3 protein, and a strong phosphorylation levels of STAT3 was statistically associated with high CSF IL-10 levels, but not with CSF IL-6 levels. Next, we demonstrated that recombinant IL-10 and CSF containing IL-10 induced the phosphorylation of STAT3 in PCNS DLBCL cells. Furthermore, molecular subtype classified by Hans' algorithm was correlated with pSTAT3 expression levels and CSF IL-10 levels. These results suggest that the STAT3 activity is correlated with CSF IL-10 level, which is a useful marker for STAT3 activity in PCNS DLBCLs.

  9. Infundibulo-hypophysitis-like radiological image in a patient with pituitary infiltration of a diffuse large B-cell non-Hodgkin lymphoma

    Directory of Open Access Journals (Sweden)

    A León-Suárez

    2016-12-01

    Full Text Available Non-Hodgkin lymphoma (NHL is a hematological tumor caused by abnormal lymphoid proliferation. NHL can arise in any part of the body, including central nervous system (CNS. However, pituitary involvement is a quite rare presentation. The diffuse large B-cell lymphoma (DLBCL is the most common subtype when pituitary is infiltrated. Here, we report a case of pituitary infiltration of NHL DLBCL type in a woman with hypopituitarism and an infundibulum-hypophysitis-like image on magnetic resonance imaging (MRI. A female aged 64 years, complained of dyspepsia, fatigue, weight loss and urine volume increment with thirst. Endoscopy and gastric biopsy confirmed diffuse large B-cell lymphoma. Treatment with chemotherapy using R-CHOP was initiated. During her hospitalization, hypotension and polyuria were confirmed. Hormonal evaluation was compatible with central diabetes insipidus and hypopituitarism. Simple T1 sequence of MRI showed thickening of the infundibular stalk with homogeneous enhancement. After lumbar puncture analysis, CNS infiltration was confirmed showing positive atypical lymphocytes. Pituitary and infundibular stalk size normalized after R-CHOP chemotherapy treatment. In conclusion, pituitary infiltration of NHL with infundibular-hypophysitis-like image on MRI is a rare finding. Clinical picture included hypopituitarism and central diabetes insipidus. Diagnosis should be suspected after biochemical analysis and MRI results. Treatment consists of chemotherapy against NHL and hormonal replacement for pituitary dysfunction.

  10. Insights into the Molecular Pathogenesis of Activated B-Cell-like Diffuse Large B-Cell Lymphoma and Its Therapeutic Implications

    Directory of Open Access Journals (Sweden)

    Georg Lenz

    2015-05-01

    Full Text Available Within the last couple of years, the understanding of the molecular mechanisms that drive the pathogenesis of diffuse large B-cell lymphoma (DLBCL has significantly improved. Large-scale gene expression profiling studies have led to the discovery of several molecularly defined subtypes that are characterized by specific oncogene addictions and significant differences in their outcome. Next generation sequencing efforts combined with RNA interference screens frequently identify crucial oncogenes that lead to constitutive activation of various signaling pathways that drive lymphomagenesis. This review summarizes our current understanding of the molecular pathogenesis of the activated B-cell-like (ABC DLBCL subtype that is characterized by poor prognosis. A special emphasis is put on findings that might impact therapeutic strategies of affected patients.

  11. Insights into the Molecular Pathogenesis of Activated B-Cell-like Diffuse Large B-Cell Lymphoma and Its Therapeutic Implications

    Energy Technology Data Exchange (ETDEWEB)

    Lenz, Georg [Translational Oncology, Department of Medicine A, Albert-Schweitzer Campus 1, University Hospital Münster, 48149 Münster (Germany); Cluster of Excellence EXC 1003, Cells in Motion, 48149 Münster (Germany)

    2015-05-22

    Within the last couple of years, the understanding of the molecular mechanisms that drive the pathogenesis of diffuse large B-cell lymphoma (DLBCL) has significantly improved. Large-scale gene expression profiling studies have led to the discovery of several molecularly defined subtypes that are characterized by specific oncogene addictions and significant differences in their outcome. Next generation sequencing efforts combined with RNA interference screens frequently identify crucial oncogenes that lead to constitutive activation of various signaling pathways that drive lymphomagenesis. This review summarizes our current understanding of the molecular pathogenesis of the activated B-cell-like (ABC) DLBCL subtype that is characterized by poor prognosis. A special emphasis is put on findings that might impact therapeutic strategies of affected patients.

  12. Bone marrow vascular endothelial growth factor level per platelet count might be a significant predictor for the treatment outcomes of patients with diffuse large B-cell lymphomas.

    Science.gov (United States)

    Kim, Jung Sun; Gang, Ga Won; Lee, Se Ryun; Sung, Hwa Jung; Park, Young; Kim, Dae Sik; Choi, Chul Won; Kim, Byung Soo

    2015-10-01

    Developing a parameter to predict bone marrow invasion by non-Hodgkin's lymphoma is an important unmet medical need for treatment decisions. This study aimed to confirm the validity of the hypothesis that bone marrow plasma vascular endothelial growth factor level might be correlated with the risk of bone marrow involvement and the prognosis of patients with diffuse large B-cell non-Hodgkin's lymphoma. Forty-nine diffuse large B-cell lymphoma patients treated with rituximab, cyclophosphamide, daunorubicin, vincristine and prednisolone regimen were enrolled. Vascular endothelial growth factor level was measured with enzyme-linked immunosorbent assay. The validity of bone marrow plasma vascular endothelial growth factor level and bone marrow vascular endothelial growth factor level per platelet count for predicting treatment response and survival after initial rituximab, cyclophosphamide, daunorubicin, vincristine and prednisolone combined chemotherapy was assessed. Bone marrow plasma vascular endothelial growth factor level per platelet count was significantly associated with old age (≥ 65 years), poor performance score (≥ 2), high International prognosis index (≥ 3) and bone marrow invasion. The patients with high bone marrow plasma vascular endothelial growth factor level per platelet count (≥ 3.01) showed a significantly lower complete response rate than the others. On Kaplan-Meier survival curves, the patients with high bone marrow plasma vascular endothelial growth factor levels (≥ 655 pg/ml) or high bone marrow plasma vascular endothelial growth factor level per platelet count (≥ 3.01) demonstrated a significantly shorter overall survival and progression-free survival than the others. In the patients without bone marrow involvement, bone marrow plasma vascular endothelial growth factor level per platelet count had a significant relationship with overall survival and progression-free survival. Multivariate analysis revealed that the patients without

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

    Science.gov (United States)

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

    2006-10-19

    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. 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. 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.

  14. Unilateral uveitis masquerade syndrome caused by diffuse large B-cell lymphoma diagnosed using multiparametric flow cytometry of the aqueous humor.

    Science.gov (United States)

    Monsalvo, Silvia; Serrano, Cristina; Prieto, Elena; Fernández-Sanz, Guillermo; Puente, Maria-Camino; Rodriguez-Pinilla, Maria; Garcia Raso, Aranzazu; Llamas, Pilar; Cordoba, Raul

    2017-07-01

    The uveitis masquerade syndromes (UMS) are a group of ocular diseases that may mimic chronic intraocular inflammation. Many malignant entities such as non-Hodgkin's lymphomas may masquerade as uveitis. We report a case of an HIV-positive patient with masquerade syndrome presenting unilateral uveitis. 45-year-old Caucasian man with a diagnosis of diffuse large B-cell lymphoma (DLBCL). The patient was diagnosed by a biopsy of an abdominal mass which showed fragments of gastric mucosa with diffuse growth of neoplastic cells. At diagnosis, the patient suffered from unilateral blurring of vision and a sudden decrease of left-eye visual acuity. A slit-lamp examination of the left eye revealed a diagnosis of anterior uveitis. The patient exhibited no signs of posterior uveitis. An anterior-chamber paracentesis was performed and analyzed by multiparameter flow cytometry (MFC), showing cells CD45, CD19, CD20, CD22, and CD38 positives, and moderate expression of CD10 with kappa light chain restriction, showing a monoclonal B-cell population. The patient received CHOP-R with intrathecal methotrexate followed by consolidation high dose methotrexate obtaining a complete response which is ongoing. Differential diagnosis between chronic uveitis and ocular lymphoma may be challenging. We advocate anterior-chamber paracentesis in cases of refractory uveitis in patients with hematologic malignancies. © 2016 International Clinical Cytometry Society. © 2016 International Clinical Cytometry Society.

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

    Directory of Open Access Journals (Sweden)

    Dehghani Mehdi

    2006-01-01

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

  16. Large-Time Behavior of Solutions to Vlasov-Poisson-Fokker-Planck Equations: From Evanescent Collisions to Diffusive Limit

    Science.gov (United States)

    Herda, Maxime; Rodrigues, L. Miguel

    2018-03-01

    The present contribution investigates the dynamics generated by the two-dimensional Vlasov-Poisson-Fokker-Planck equation for charged particles in a steady inhomogeneous background of opposite charges. We provide global in time estimates that are uniform with respect to initial data taken in a bounded set of a weighted L^2 space, and where dependencies on the mean-free path τ and the Debye length δ are made explicit. In our analysis the mean free path covers the full range of possible values: from the regime of evanescent collisions τ → ∞ to the strongly collisional regime τ → 0. As a counterpart, the largeness of the Debye length, that enforces a weakly nonlinear regime, is used to close our nonlinear estimates. Accordingly we pay a special attention to relax as much as possible the τ -dependent constraint on δ ensuring exponential decay with explicit τ -dependent rates towards the stationary solution. In the strongly collisional limit τ → 0, we also examine all possible asymptotic regimes selected by a choice of observation time scale. Here also, our emphasis is on strong convergence, uniformity with respect to time and to initial data in bounded sets of a L^2 space. Our proofs rely on a detailed study of the nonlinear elliptic equation defining stationary solutions and a careful tracking and optimization of parameter dependencies of hypocoercive/hypoelliptic estimates.

  17. Diffuse large B-cell lymphoma associated with the use of biologic and other investigational agents: the importance of long-term post-marketing safety surveillance.

    Science.gov (United States)

    Goddard, Allison; Borovicka, Judy H; West, Dennis P; Evens, Andrew M; Laumann, Anne

    2011-01-01

    This case report describes a patient who developed diffuse large B-cell lymphoma (DLBCL) after receiving courses of two investigational biologic agents and cyclosporine followed by more than four years of subcutaneous efalizumab for the treatment of extensive chronic plaque psoriasis. Three years later, the patient remains free of lymphoma and his psoriasis is well controlled with thrice-weekly narrow-band ultraviolet phototherapy. This case emphasizes the importance of continued long-term post-marketing safety surveillance and the early reporting of all possible serious side effects, including cancers, related to the use of any newly available product. In particular, surveillance should focus on the immunomodulating biologic agents in order to identify possible dangerous sequelae.

  18. Reduced expression of TRIM21/Ro52 predicts poor prognosis in diffuse large B-cell lymphoma patients with and without rheumatic disease

    DEFF Research Database (Denmark)

    Brauner, S; Zhou, W; Backlin, C

    2015-01-01

    OBJECTIVE: TRIM21 (also known as Ro52) is an autoantigen in rheumatic disease and is predominantly expressed in leucocytes. Overexpression is associated with decreased proliferation, and the TRIM21 gene maps to a tumour suppressor locus. We therefore investigated the expression of TRIM21...... in patients with diffuse large B-cell lymphoma (DLBCL) and its potential usefulness as a prognostic biomarker. MATERIALS AND METHODS: TRIM21 expression levels were assessed by immunohistochemistry in lymphoma biopsies from three cohorts of patients with DLBCL: 42 patients with rheumatic disease treated...... with a cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP)-like regimen, 76 CHOP-treated and 196 rituximab-CHOP-treated nonrheumatic patients. Expression was correlated with clinical and biomedical parameters. TRIM21 expression was assessed in relation to lymphocyte proliferation by quantitative PCR...

  19. FOXP1 suppresses immune response signatures and MHC class II expression in activated B-cell-like diffuse large B-cell lymphomas

    DEFF Research Database (Denmark)

    Brown, P J; Wong, K K; Felce, S L

    2016-01-01

    The FOXP1 (forkhead box P1) transcription factor is a marker of poor prognosis in diffuse large B-cell lymphoma (DLBCL). Here microarray analysis of FOXP1-silenced DLBCL cell lines identified differential regulation of immune response signatures and major histocompatibility complex class II (MHC II......) genes as some of the most significant differences between germinal center B-cell (GCB)-like DLBCL with full-length FOXP1 protein expression versus activated B-cell (ABC)-like DLBCL expressing predominantly short FOXP1 isoforms. In an independent primary DLBCL microarray data set, multiple MHC II genes......, including human leukocyte antigen DR alpha chain (HLA-DRA), were inversely correlated with FOXP1 transcript expression (PABC-DLBCL cells led to increased cell-surface expression of HLA-DRA and CD74. In R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone...

  20. Sunitinib in relapsed or refractory diffuse large B-cell lymphoma: a clinical and pharmacodynamic phase II multicenter study of the NCIC Clinical Trials Group.

    Science.gov (United States)

    Buckstein, Rena; Kuruvilla, John; Chua, Neil; Lee, Christina; Macdonald, David A; Al-Tourah, Abdulwahab J; Foo, Alison H; Walsh, Wendy; Ivy, S Percy; Crump, Michael; Eisenhauer, Elizabeth A

    2011-05-01

    There are limited effective therapies for most patients with relapsed diffuse large B-cell lymphoma (DLBCL). We conducted a phase II trial of the multi-targeted vascular endothelial growth factor receptor (VEGFR) kinase inhibitor, sunitinib, 37.5 mg given orally once daily in adult patients with relapsed or refractory DLBCL. Of 19 enrolled patients, 17 eligible patients were evaluable for toxicity and 15 for response. No objective responses were seen and nine patients achieved stable disease (median duration 3.4 months). As a result, the study was closed at the end of the first stage. Grades 3-4 neutropenia and thrombocytopenia were observed in 29% and 35%, respectively. There was no relationship between change in circulating endothelial cell numbers (CECs) and bidimensional tumor burden over time. Despite some activity in solid tumors, sunitinib showed no evidence of response in relapsed/refractory DLBCL and had greater than expected hematologic toxicity.

  1. DNMT1 is predictive of survival and associated with Ki-67 expression in R-CHOP-treated diffuse large B-cell lymphomas

    DEFF Research Database (Denmark)

    Loo, Suet Kee; Ch'ng, Ewe Seng; Lawrie, Charles H

    2017-01-01

    .9%) with higher expression in germinal centre B-cell-like (GCB)-DLBCL subtype. Low and negative DNMT1 expression (20% cut-off, n = 33/230, 14.3%) was predictive of worse overall survival (OS; p p ...DNMT1 is a target of approved anti-cancer drugs including decitabine. However, the prognostic value of DNMT1 protein expression in R-CHOP-treated diffuse large B-cell lymphomas (DLBCLs) remains unexplored. Here we showed that DNMT1 was expressed in the majority of DLBCL cases (n = 209/230, 90......% did not achieve 5-year OS and PFS, respectively, indicating that DNMT1 positive patients showed considerably heterogeneous outcomes. Moreover, DNMT1 was frequently expressed in mitotic cells and significantly correlated with Ki-67 or BCL6 expression (r = 0.60 or 0.44, respectively; p

  2. Randomized Trial Comparing R-CHOP Versus High-Dose Sequential Chemotherapy in High-Risk Patients With Diffuse Large B-Cell Lymphomas.

    Science.gov (United States)

    Cortelazzo, Sergio; Tarella, Corrado; Gianni, Alessandro Massimo; Ladetto, Marco; Barbui, Anna Maria; Rossi, Andrea; Gritti, Giuseppe; Corradini, Paolo; Di Nicola, Massimo; Patti, Caterina; Mulé, Antonino; Zanni, Manuela; Zoli, Valerio; Billio, Atto; Piccin, Andrea; Negri, Giovanni; Castellino, Claudia; Di Raimondo, Francesco; Ferreri, Andrés J M; Benedetti, Fabio; La Nasa, Giorgio; Gini, Guido; Trentin, Livio; Frezzato, Maurizio; Flenghi, Leonardo; Falorio, Simona; Chilosi, Marco; Bruna, Riccardo; Tabanelli, Valentina; Pileri, Stefano; Masciulli, Arianna; Delaini, Federica; Boschini, Cristina; Rambaldi, Alessandro

    2016-11-20

    Purpose The benefit of high-dose chemotherapy with autologous stem-cell transplantation (ASCT) as first-line treatment in patients with diffuse large B-cell lymphomas is still a matter of debate. To address this point, we designed a randomized phase III trial to compare rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)-14 (eight cycles) with rituximab plus high-dose sequential chemotherapy (R-HDS) with ASCT. Patients and Methods From June 2005 to June 2011, 246 high-risk patients with a high-intermediate (56%) or high (44%) International Prognostic Index score were randomly assigned to the R-CHOP or R-HDS arm, and 235 were analyzed by intent to treat. The primary efficacy end point of the study was 3-year event-free survival, and results were analyzed on an intent-to-treat basis. Results Clinical response (complete response, 78% v 76%; partial response, 5% v 9%) and failures (no response, 15% v 11%; and early treatment-related mortality, 2% v 3%) were similar after R-CHOP versus R-HDS, respectively. After a median follow-up of 5 years, the 3-year event-free survival was 62% versus 65% ( P = .83). At 3 years, compared with the R-CHOP arm, the R-HDS arm had better disease-free survival (79% v 91%, respectively; P = .034), but this subsequently vanished because of late-occurring treatment-related deaths. No difference was detected in terms of progression-free survival (65% v 75%, respectively; P = .12), or overall survival (74% v 77%, respectively; P = .64). Significantly higher hematologic toxicity ( P < .001) and more infectious complications ( P < .001) were observed in the R-HDS arm. Conclusion In this study, front-line intensive R-HDS chemotherapy with ASCT did not improve the outcome of high-risk patients with diffuse large B-cell lymphomas.

  3. The impact of changes in parameterizations of surface drag and vertical diffusion on the large-scale circulation in the Community Atmosphere Model (CAM5)

    Science.gov (United States)

    Lindvall, Jenny; Svensson, Gunilla; Caballero, Rodrigo

    2017-06-01

    Simulations with the Community Atmosphere Model version 5 (CAM5) are used to analyze the sensitivity of the large-scale circulation to changes in parameterizations of orographic surface drag and vertical diffusion. Many GCMs and NWP models use enhanced turbulent mixing in stable conditions to improve simulations, while CAM5 cuts off all turbulence at high stabilities and instead employs a strong orographic surface stress parameterization, known as turbulent mountain stress (TMS). TMS completely dominates the surface stress over land and reduces the near-surface wind speeds compared to simulations without TMS. It is found that TMS is generally beneficial for the large-scale circulation as it improves zonal wind speeds, Arctic sea level pressure and zonal anomalies of the 500-hPa stream function, compared to ERA-Interim. It also alleviates atmospheric blocking frequency biases in the Northern Hemisphere. Using a scheme that instead allows for a modest increase of turbulent diffusion at higher stabilities only in the planetary boundary layer (PBL) appears to in some aspects have a similar, although much smaller, beneficial effect as TMS. Enhanced mixing throughout the atmospheric column, however, degrades the CAM5 simulation. Evaluating the simulations in comparison with detailed measurements at two locations reveals that TMS is detrimental for the PBL at the flat grassland ARM Southern Great Plains site, giving too strong wind turning and too deep PBLs. At the Sodankylä forest site, the effect of TMS is smaller due to the larger local vegetation roughness. At both sites, all simulations substantially overestimate the boundary layer ageostrophic flow.

  4. Expression of CD40 is a positive prognostic factor of diffuse large B-cell lymphoma treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone

    Directory of Open Access Journals (Sweden)

    Song G

    2016-06-01

    Full Text Available Guoqi Song,1 Huiyun Ni,1 Linqing Zou,2 Shukui Wang,3 Fuliang Tian,4 Hong Liu,1 William C Cho5 1Department of Hematology, Affiliated Hospital of Nantong University, Nantong, 2Department of Human Anatomy, Nantong University, Nantong, 3Central Laboratory of Nanjing First Hospital, Nanjing Medical University, Nanjing, 4Maternal and Child Health Hospital of Lianyungang, Lianyungang, Jiangsu, People’s Republic of China; 5Department of Clinical Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong Objectives: The objective of this study was to investigate the expression level of CD40 and its role in the prognosis of patients with diffuse large B-cell lymphoma (DLBCL who were treated with rituximab-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone.Design and methods: The immunohistochemical expressions of CD40 in 186 well-characterized DLBCL patients were evaluated by tissue microarrays, thereby revealing the relationship of the molecule CD40 with known tumor, patient-related variables, and survival rates.Results: The results showed that CD40 expressions were not statistically different between the germinal center B-cell-like (GCB type and the non-GCB type. We also analyzed the relationships of CD40 expression with overall survival (OS and progression-free survival (PFS in DLBCL patients who were uniformly treated with R-CHOP. A low expression of CD40 compared to high expression is related to poor OS and PFS. Conclusion: Our findings indicate that the CD40 level at onset acts as an independent prognostic predictor of DLBCL patients treated with R-CHOP. Keywords: CD40, diffuse large B-cell lymphoma, R-CHOP, prognostic factor

  5. GWAS of follicular lymphoma reveals allelic heterogeneity at 6p21.32 and suggests shared genetic susceptibility with diffuse large B-cell lymphoma.

    Directory of Open Access Journals (Sweden)

    Karin E Smedby

    2011-04-01

    Full Text Available Non-Hodgkin lymphoma (NHL represents a diverse group of hematological malignancies, of which follicular lymphoma (FL is a prevalent subtype. A previous genome-wide association study has established a marker, rs10484561 in the human leukocyte antigen (HLA class II region on 6p21.32 associated with increased FL risk. Here, in a three-stage genome-wide association study, starting with a genome-wide scan of 379 FL cases and 791 controls followed by validation in 1,049 cases and 5,790 controls, we identified a second independent FL-associated locus on 6p21.32, rs2647012 (OR(combined  = 0.64, P(combined  = 2 × 10(-21 located 962 bp away from rs10484561 (r(2<0.1 in controls. After mutual adjustment, the associations at the two SNPs remained genome-wide significant (rs2647012:OR(adjusted  = 0.70, P(adjusted  =  4 × 10(-12; rs10484561:OR(adjusted  = 1.64, P(adjusted  = 5 × 10(-15. Haplotype and coalescence analyses indicated that rs2647012 arose on an evolutionarily distinct haplotype from that of rs10484561 and tags a novel allele with an opposite (protective effect on FL risk. Moreover, in a follow-up analysis of the top 6 FL-associated SNPs in 4,449 cases of other NHL subtypes, rs10484561 was associated with risk of diffuse large B-cell lymphoma (OR(combined  = 1.36, P(combined  =  1.4 × 10(-7. Our results reveal the presence of allelic heterogeneity within the HLA class II region influencing FL susceptibility and indicate a possible shared genetic etiology with diffuse large B-cell lymphoma. These findings suggest that the HLA class II region plays a complex yet important role in NHL.

  6. Experimental investigations on bubble turbulent diffusion in a vertical large diameter pipe by means of wire-mesh sensors and correlation techniques

    International Nuclear Information System (INIS)

    Annalisa Manera; Horst-Michael Prasser; Dirk Lucas

    2005-01-01

    Full text of publication follows: A large number of experiments for water-air vertical flows in a large-diameter pipe has been carried out at the TOPFLOW facility (Forschunszentrum Rossendorf). The experiments cover a wide range of liquid and superficial gas velocity. The test section consists of a vertical pipe of ∼194 mm and 8.5 m long. At a distance of 7.6 m from the air injection, two wire-mesh sensors are installed. The two sensors are mounted at a distance of 63.3 mm from each other. The wire-mesh sensors measure sequences of instantaneous two-dimensional gas-fraction distributions in the cross-section in which they are mounted with a spatial resolution of 3 mm and a frequency of 2500 Hz. The total dimension of the matrix of measuring points for each mesh sensor is 64 x 64. In a central region of the measuring plane, where the void-fraction gradients are small, points of the first wire-mesh sensor are individually cross-correlated in time domain with measuring points belonging to the second wire-mesh sensor. The cross-correlation functions were calculated for pairs of points that are located accurately above each other as well as for points with a lateral distance. The lateral distance was varied from 0 to 48 mm (16 points), which is still within 50% of the pipe radius, i.e. in the region of small void-fraction gradients. The maximum of each of the 17 correlations is selected in order to derive a spatial correlation in the radial direction. The obtained spatial cross-correlations shows a maximum at zero lateral distance and decrease with growing lateral shift. In a region without gradients, the lateral displacement of bubbles is dominated by turbulent diffusion. This gives the opportunity to derive bubble turbulent diffusion coefficients from the spreading of the spatial correlations. At this aim, the spatial correlations have been first corrected to take into account the finite spatial resolution of the sensor and the finite dimension of the bubbles. The

  7. Large scale simulation of liquid water transport in a gas diffusion layer of polymer electrolyte membrane fuel cells using the lattice Boltzmann method

    Science.gov (United States)

    Sakaida, Satoshi; Tabe, Yutaka; Chikahisa, Takemi

    2017-09-01

    A method for the large-scale simulation with the lattice Boltzmann method (LBM) is proposed for liquid water movement in a gas diffusion layer (GDL) of polymer electrolyte membrane fuel cells. The LBM is able to analyze two-phase flows in complex structures, however the simulation domain is limited due to heavy computational loads. This study investigates a variety means to reduce computational loads and increase the simulation areas. One is applying an LBM treating two-phases as having the same density, together with keeping numerical stability with large time steps. The applicability of this approach is confirmed by comparing the results with rigorous simulations using actual density. The second is establishing the maximum limit of the Capillary number that maintains flow patterns similar to the precise simulation; this is attempted as the computational load is inversely proportional to the Capillary number. The results show that the Capillary number can be increased to 3.0 × 10-3, where the actual operation corresponds to Ca = 10-5∼10-8. The limit is also investigated experimentally using an enlarged scale model satisfying similarity conditions for the flow. Finally, a demonstration is made of the effects of pore uniformity in GDL as an example of a large-scale simulation covering a channel.

  8. PD-1 Blockade Can Restore Functions of T-Cells in Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma In Vitro.

    Directory of Open Access Journals (Sweden)

    Lina Quan

    Full Text Available Epstein-Barr virus-positive diffuse large B-cell lymphoma (EBV+DLBCL is an aggressive malignancy that is largely resistant to current therapeutic regimens, and is an attractive target for immune-based therapies. Anti-programmed death-1 (PD-1 antibodies showed encouraging anti-tumor effects in both preclinical models and advanced solid and hematological malignancies, but its efficacy against EBV+DLBCL is unknown. Herein, we performed experiments using co-culture system with T cells and lymphoma cell lines including EBV+DLBCL and EBV-DLBCL [including germinal center B-cell like (GCB-DLBCL and non-GCB-DLBCL] in vitro. We show that lymphoma cells augmented the expression of PD-1 on T cells, decreased the proliferation of T cells, and altered the secretion of multiple cytokines. However, through PD-1 blockade, these functions could be largely restored. Notbaly, the effect of PD-1 blockade on antitumor immunity was more effective in EBV+DLBCL than that in EBV-DLBCL in vitro. These results suggest that T-cell exhaustion and immune escape in microenvironment is one of the mechanisms underlying DLBCL; and PD-1 blockade could present as a efficacious immunotherapeutic treatment for EBV+DLBCL.

  9. Bone marrow involvement in diffuse large B-cell lymphoma: correlation between FDG-PET uptake and type of cellular infiltrate

    International Nuclear Information System (INIS)

    Paone, Gaetano; Itti, Emmanuel; Lin, Chieh; Meignan, Michel; Haioun, Corinne; Dupuis, Jehan; Gaulard, Philippe

    2009-01-01

    To assess, in patients with diffuse large B-cell lymphoma (DLBCL), whether the low sensitivity of 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) for bone marrow assessment may be explained by histological characteristics of the cellular infiltrate. From a prospective cohort of 110 patients with newly diagnosed aggressive lymphoma, 21 patients with DLBCL had bone marrow involvement. Pretherapeutic FDG-PET images were interpreted visually and semiquantitatively, then correlated with the type of cellular infiltrate and known prognostic factors. Of these 21 patients, 7 (33%) had lymphoid infiltrates with a prominent component of large transformed lymphoid cells (concordant bone marrow involvement, CBMI) and 14 (67%) had lymphoid infiltrates composed of small cells (discordant bone marrow involvement, DBMI). Only 10 patients (48%) had abnormal bone marrow FDG uptake, 6 of the 7 with CBMI and 4 of the 14 with DBMI. Therefore, FDG-PET positivity in the bone marrow was significantly associated with CBMI, while FDG-PET negativity was associated with DBMI (Fisher's exact test, p=0.024). There were no significant differences in gender, age and overall survival between patients with CBMI and DBMI, while the international prognostic index was significantly higher in patients with CBMI. Our study suggests that in patients with DLBCL with bone marrow involvement bone marrow FDG uptake depends on two types of infiltrate, comprising small (DBMI) or large (CBMI) cells. This may explain the apparent low sensitivity of FDG-PET previously reported for detecting bone marrow involvement. (orig.)

  10. Large Interstellar Polarisation Survey. II. UV/optical study of cloud-to-cloud variations of dust in the diffuse ISM

    Science.gov (United States)

    Siebenmorgen, R.; Voshchinnikov, N. V.; Bagnulo, S.; Cox, N. L. J.; Cami, J.; Peest, C.

    2018-03-01

    It is well known that the dust properties of the diffuse interstellar medium exhibit variations towards different sight-lines on a large scale. We have investigated the variability of the dust characteristics on a small scale, and from cloud-to-cloud. We use low-resolution spectro-polarimetric data obtained in the context of the Large Interstellar Polarisation Survey (LIPS) towards 59 sight-lines in the Southern Hemisphere, and we fit these data using a dust model composed of silicate and carbon particles with sizes from the molecular to the sub-micrometre domain. Large (≥6 nm) silicates of prolate shape account for the observed polarisation. For 32 sight-lines we complement our data set with UVES archive high-resolution spectra, which enable us to establish the presence of single-cloud or multiple-clouds towards individual sight-lines. We find that the majority of these 35 sight-lines intersect two or more clouds, while eight of them are dominated by a single absorbing cloud. We confirm several correlations between extinction and parameters of the Serkowski law with dust parameters, but we also find previously undetected correlations between these parameters that are valid only in single-cloud sight-lines. We find that interstellar polarisation from multiple-clouds is smaller than from single-cloud sight-lines, showing that the presence of a second or more clouds depolarises the incoming radiation. We find large variations of the dust characteristics from cloud-to-cloud. However, when we average a sufficiently large number of clouds in single-cloud or multiple-cloud sight-lines, we always retrieve similar mean dust parameters. The typical dust abundances of the single-cloud cases are [C]/[H] = 92 ppm and [Si]/[H] = 20 ppm.

  11. MDM2 phenotypic and genotypic profiling, respective to TP53 genetic status, in diffuse large B-cell lymphoma patients treated with rituximab-CHOP immunochemotherapy: a report from the International DLBCL Rituximab-CHOP Consortium Program

    NARCIS (Netherlands)

    Xu-Monette, Z.Y.; Moller, M.B.; Tzankov, A.; Montes-Moreno, S.; Hu, W.; Manyam, G.C.; Kristensen, L.; Fan, L.; Visco, C.; Dybkaer, K.; Chiu, A.; Tam, W.; Zu, Y.; Bhagat, G.; Richards, K.L.; Hsi, E.D.; Choi, W.W.; Krieken, J.H.J.M. van; Huang, Q.; Huh, J.; Ai, W.; Ponzoni, M.; Ferreri, A.J.; Wu, L.; Zhao, X.; Bueso-Ramos, C.E.; Wang, S.A.; Go, R.S.; Li, Y.; Winter, J.N.; Piris, M.A.; Medeiros, L.J.; Young, K.H.

    2013-01-01

    MDM2 is a key negative regulator of the tumor suppressor p53, however, the prognostic significance of MDM2 overexpression in diffuse large B-cell lymphoma (DLBCL) has not been defined convincingly. In a p53 genetically-defined large cohort of de novo DLBCL patients treated with rituximab,

  12. A new extranodal scoring system based on the prognostically relevant extranodal sites in diffuse large B-cell lymphoma, not otherwise specified treated with chemoimmunotherapy.

    Science.gov (United States)

    Hwang, Hee Sang; Yoon, Dok Hyun; Suh, Cheolwon; Huh, Jooryung

    2016-08-01

    Extranodal involvement is a well-known prognostic factor in patients with diffuse large B-cell lymphomas (DLBCL). Nevertheless, the prognostic impact of the extranodal scoring system included in the conventional international prognostic index (IPI) has been questioned in an era where rituximab treatment has become widespread. We investigated the prognostic impacts of individual sites of extranodal involvement in 761 patients with DLBCL who received rituximab-based chemoimmunotherapy. Subsequently, we established a new extranodal scoring system based on extranodal sites, showing significant prognostic correlation, and compared this system with conventional scoring systems, such as the IPI and the National Comprehensive Cancer Network-IPI (NCCN-IPI). An internal validation procedure, using bootstrapped samples, was also performed for both univariate and multivariate models. Using multivariate analysis with a backward variable selection, we found nine extranodal sites (the liver, lung, spleen, central nervous system, bone marrow, kidney, skin, adrenal glands, and peritoneum) that remained significant for use in the final model. Our newly established extranodal scoring system, based on these sites, was better correlated with patient survival than standard scoring systems, such as the IPI and the NCCN-IPI. Internal validation by bootstrapping demonstrated an improvement in model performance of our modified extranodal scoring system. Our new extranodal scoring system, based on the prognostically relevant sites, may improve the performance of conventional prognostic models of DLBCL in the rituximab era and warrants further external validation using large study populations.

  13. Promoter methylation patterns in Richter syndrome affect stem-cell maintenance and cell cycle regulation and differ from de novo diffuse large B-cell lymphoma.

    Science.gov (United States)

    Rinaldi, Andrea; Mensah, Afua Adjeiwaa; Kwee, Ivo; Forconi, Francesco; Orlandi, Ester M; Lucioni, Marco; Gattei, Valter; Marasca, Roberto; Berger, Françoise; Cogliatti, Sergio; Cavalli, Franco; Zucca, Emanuele; Gaidano, Gianluca; Rossi, Davide; Bertoni, Francesco

    2013-10-01

    In a fraction of patients, chronic lymphocytic leukaemia (CLL) can transform to Richter syndrome (RS), usually a diffuse large B-cell lymphoma (DLBCL). We studied genome-wide promoter DNA methylation in RS and clonally related CLL-phases of transformed patients, alongside de novo DLBCL (of non-germinal centre B type), untransformed-CLL and normal B-cells. The greatest differences in global DNA methylation levels were observed between RS and DLBCL, indicating that these two diseases, although histologically similar, are epigenetically distinct. RS was more highly methylated for genes involved in cell cycle regulation. When RS was compared to the preceding CLL-phase and with untransformed-CLL, RS presented a higher degree of methylation for genes possessing the H3K27me3 mark and PRC2 targets, as well as for gene targets of TP53 and RB1. Comparison of the methylation levels of individual genes revealed that OSM, a stem cell regulatory gene, exhibited significantly higher methylation levels in RS compared to CLL-phases. Its transcriptional repression by DNA methylation was confirmed by 5-aza-2'deoxycytidine treatment of DLBCL cells, determining an increased OSM expression. Our results showed that methylation patterns in RS are largely different from de novo DLBCL. Stem cell-related genes and cell cycle regulation genes are targets of DNA methylation in RS. © 2013 John Wiley & Sons Ltd.

  14. CD3+/CD16+CD56+ cell numbers in peripheral blood are correlated with higher tumor burden in patients with diffuse large B-cell lymphoma

    Directory of Open Access Journals (Sweden)

    Anna Twardosz

    2011-04-01

    Full Text Available Diffuse large B-cell lymphoma is the commonest histological type of malignant lymphoma, andremains incurable in many cases. Developing more efficient immunotherapy strategies will require betterunderstanding of the disorders of immune responses in cancer patients. NKT (natural killer-like T cells wereoriginally described as a unique population of T cells with the co-expression of NK cell markers. Apart fromtheir role in protecting against microbial pathogens and controlling autoimmune diseases, NKT cells havebeen recently revealed as one of the key players in the immune responses against tumors. The objective of thisstudy was to evaluate the frequency of CD3+/CD16+CD56+ cells in the peripheral blood of 28 diffuse largeB-cell lymphoma (DLBCL patients in correlation with clinical and laboratory parameters. Median percentagesof CD3+/CD16+CD56+ were significantly lower in patients with DLBCL compared to healthy donors(7.37% vs. 9.01%, p = 0.01; 4.60% vs. 5.81%, p = 0.03, although there were no differences in absolute counts.The frequency and the absolute numbers of CD3+/CD16+CD56+ cells were lower in advanced clinical stagesthan in earlier ones. The median percentage of CD3+/CD16+CD56+ cells in patients in Ann Arbor stages 1–2 was5.55% vs. 3.15% in stages 3–4 (p = 0.02, with median absolute counts respectively 0.26 G/L vs. 0.41 G/L (p == 0.02. The percentage and absolute numbers of CD3+/CD16+CD56+ cells were significantly higher in DL-BCL patients without B-symptoms compared to the patients with B-symptoms, (5.51% vs. 2.46%, p = 0.04;0.21 G/L vs. 0.44 G/L, p = 0.04. The percentage of CD3+/CD16+CD56+ cells correlated adversely with serumlactate dehydrogenase (R= –445; p < 0.05 which might influence NKT count. These figures suggest a relationshipbetween higher tumor burden and more aggressive disease and decreased NKT numbers. But it remains tobe explained whether low NKT cell counts in the peripheral blood of patients with DLBCL are the result

  15. Genomic profiling using array comparative genomic hybridization define distinct subtypes of diffuse large b-cell lymphoma: a review of the literature

    Directory of Open Access Journals (Sweden)

    Tirado Carlos A

    2012-09-01

    Full Text Available Abstract Diffuse large B-cell lymphoma (DLBCL is the most common type of non-Hodgkin Lymphoma comprising of greater than 30% of adult non-Hodgkin Lymphomas. DLBCL represents a diverse set of lymphomas, defined as diffuse proliferation of large B lymphoid cells. Numerous cytogenetic studies including karyotypes and fluorescent in situ hybridization (FISH, as well as morphological, biological, clinical, microarray and sequencing technologies have attempted to categorize DLBCL into morphological variants, molecular and immunophenotypic subgroups, as well as distinct disease entities. Despite such efforts, most lymphoma remains undistinguishable and falls into DLBCL, not otherwise specified (DLBCL-NOS. The advent of microarray-based studies (chromosome, RNA, gene expression, etc has provided a plethora of high-resolution data that could potentially facilitate the finer classification of DLBCL. This review covers the microarray data currently published for DLBCL. We will focus on these types of data; 1 array based CGH; 2 classical CGH; and 3 gene expression profiling studies. The aims of this review were three-fold: (1 to catalog chromosome loci that are present in at least 20% or more of distinct DLBCL subtypes; a detailed list of gains and losses for different subtypes was generated in a table form to illustrate specific chromosome loci affected in selected subtypes; (2 to determine common and distinct copy number alterations among the different subtypes and based on this information, characteristic and similar chromosome loci for the different subtypes were depicted in two separate chromosome ideograms; and, (3 to list re-classified subtypes and those that remained indistinguishable after review of the microarray data. To the best of our knowledge, this is the first effort to compile and review available literatures on microarray analysis data and their practical utility in classifying DLBCL subtypes. Although conventional cytogenetic methods such

  16. EBV-positive immunodeficiency lymphoma after alemtuzumab-CHOP therapy for peripheral T-cell lymphoma

    NARCIS (Netherlands)

    Kluin-Nelemans, Hanneke C.; Coenen, Jules L.; Boers, James E.; van Imhoff, Gustaaf W.; Rosati, Stefano

    2008-01-01

    Chemotherapy with alemtuzumab and the combination of cyclophosphamide, adriamycin, oncovin, and prednisone (CHOP) has become experimental trial therapy for aggressive T-cell lymphoma. Several multicenter phase 3 trials; will incorporate this scheme. As part of an ongoing phase 2 trial in which we

  17. The small FOXP1 isoform predominantly expressed in activated B cell-like diffuse large B-cell lymphoma and full-length FOXP1 exert similar oncogenic and transcriptional activity in human B cells.

    Science.gov (United States)

    van Keimpema, Martine; Grüneberg, Leonie J; Schilder-Tol, Esther J M; Oud, Monique E C M; Beuling, Esther A; Hensbergen, Paul J; de Jong, Johann; Pals, Steven T; Spaargaren, Marcel

    2017-03-01

    The forkhead transcription factor FOXP1 is generally regarded as an oncogene in activated B cell-like diffuse large B-cell lymphoma. Previous studies have suggested that a small isoform of FOXP1 rather than full-length FOXP1, may possess this oncogenic activity. Corroborating those studies, we herein show that activated B cell-like diffuse large B-cell lymphoma cell lines and primary activated B cell-like diffuse large B-cell lymphoma cells predominantly express a small FOXP1 isoform, and that the 5'-end of the Foxp1 gene is a common insertion site in murine lymphomas in leukemia virus- and transposon-mediated insertional mutagenesis screens. By combined mass spectrometry, (quantative) reverse transcription polymerase chain reaction/sequencing, and small interfering ribonucleic acid-mediated gene silencing, we determined that the small FOXP1 isoform predominantly expressed in activated B cell-like diffuse large B-cell lymphoma lacks the N-terminal 100 amino acids of full-length FOXP1. Aberrant overexpression of this FOXP1 isoform (ΔN100) in primary human B cells revealed its oncogenic capacity; it repressed apoptosis and plasma cell differentiation. However, no difference in potency was found between this small FOXP1 isoform and full-length FOXP1. Furthermore, overexpression of full-length FOXP1 or this small FOXP1 isoform in primary B cells and diffuse large B-cell lymphoma cell lines resulted in similar gene regulation. Taken together, our data indicate that this small FOXP1 isoform and full-length FOXP1 have comparable oncogenic and transcriptional activity in human B cells, suggesting that aberrant expression or overexpression of FOXP1, irrespective of the specific isoform, contributes to lymphomagenesis. These novel insights further enhance the value of FOXP1 for the diagnostics, prognostics, and treatment of diffuse large B-cell lymphoma patients. Copyright© Ferrata Storti Foundation.

  18. Return to work for patients with diffuse large B-cell lymphoma and transformed indolent lymphoma undergoing autologous stem cell transplantation

    DEFF Research Database (Denmark)

    Arboe, Bente; Olsen, Maja Halgren; Goerloev, Jette Soenderskov

    2017-01-01

    BACKGROUND: Autologous stem cell transplantation (ASCT) is the standard treatment for patients with relapsed diffuse large B-cell lymphoma (DLBCL) or transformed indolent lymphoma (TIL). The treatment is mainly considered for younger patients still available for the work market. In this study...... to work. The rate of returning to work in the first year following ASCT was decreased for patients being on sick leave at the time of relapse (hazard ratio [HR] 0.3 [0.2;0.5]) and increased for patients aged ≥55 years (HR 1.9 [1.1;3.3]). In all, 56 (27%) patients were granted disability pension. Being...... on sick leave at the time of relapse was positively associated with receiving a disability pension in the first 2 years after ASCT (HR 3.7 [1.8;7.7]). CONCLUSION: Patients on sick leave at the time of relapse have a poorer prognosis regarding RTW and have a higher rate of disability pension. Furthermore...

  19. A Case Report of Nongerminal Center B-Cell Type Diffuse Large B-Cell Lymphoma Treated to Complete Response with Rituximab and Ibrutinib

    Directory of Open Access Journals (Sweden)

    Geoffrey Shouse

    2018-01-01

    Full Text Available Diffuse large B-cell lymphoma (DLBCL is a molecularly heterogeneous disease consisting of different subtypes with varying clinical behaviors. For example, the activated B-cell-like (ABC type of DLBCL has lower cure rates with traditional chemotherapy regimens. The molecular pathway promoting tumorigenic growth of the ABC type includes a dependence on intracellular signaling by Bruton’s agammaglobulinemia tyrosine kinase (BTK. This specific pathway has led to the investigation of the utility of ibrutinib in treatment of this type of lymphoma at relapse or in combination with standard chemotherapy. In elderly patients stricken with this disease, standard combination chemotherapy can pose significant toxicity. Some reduced intensity regimens have activity but significantly less favorable long-term outcomes and still pose significant toxicity to elderly patients. In the following case, we demonstrate induction of complete response in an elderly patient with significant comorbidities with nongerminal center B-cell type (NGCB DLBCL treated with rituximab, ibrutinib, and prednisone. Toxicity included atrial fibrillation that ultimately led to heart failure as well as sepsis which ultimately led to the patient’s demise. Despite this fact, the response to treatment appeared durable. This case illustrates the utility and limitations of molecularly targeted therapies to treat aggressive lymphoma in frail elderly patients.

  20. Prognostic Value of the Pretreatment Advanced Lung Cancer Inflammation Index (ALI) in Diffuse Large B Cell Lymphoma Patients Treated with R-CHOP Chemotherapy.

    Science.gov (United States)

    Park, Young Hoon; Yi, Hyeon Gyu; Lee, Moon Hee; Kim, Chul Soo; Lim, Joo Han

    2017-01-01

    The Advanced Lung Cancer Inflammation Index (ALI, body mass index × albumin/neutrophil-to-lymphocyte ratio) has been demonstrated to be a prognostic factor of survival in some solid cancers. We retrospectively investigated the usefulness of the ALI to predict chemotherapy response and survival in 212 patients with diffuse large B cell lymphoma (DLBCL) treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy. Patients were allocated to a low ALI group (n = 82, 38.7%) or a high ALI group (n = 130, 61.3%) according to an optimal pretreatment ALI cut-off value of 15.5 as determined by receiver operating curve analysis. The low ALI group displayed more adverse clinical characteristics, lower rates of complete remission (54.9 vs. 75.4%, p = 0.008), and poorer 5-year progression-free (PFS, 58.1 vs. 77.3%, p = 0.006) and overall (OS, 64.2 vs. 80.2%, p = 0.008) survival. Multivariate analysis showed that low ALI was found to independently predict shorter PFS and OS. Interestingly, a low ALI reverted to a high ALI during treatment in 58 patients (27.4%), and the 5-year OS of these patients was better than that of patients whose ALI remained low (n = 24, 72.5 vs. 24%, p ALI might be an easily available marker for predicting clinical outcomes in DLBCL patients treated with R-CHOP chemotherapy. © 2017 S. Karger AG, Basel.

  1. Diffuse large B-cell lymphoma (Richter syndrome) in patients with chronic lymphocytic leukaemia (CLL): a cohort study of newly diagnosed patients.

    Science.gov (United States)

    Parikh, Sameer A; Rabe, Kari G; Call, Timothy G; Zent, Clive S; Habermann, Thomas M; Ding, Wei; Leis, Jose F; Schwager, Susan M; Hanson, Curtis A; Macon, William R; Kay, Neil E; Slager, Susan L; Shanafelt, Tait D

    2013-09-01

    Nearly all information about patients with chronic lymphocytic leukaemia (CLL) who develop diffuse large B-cell lymphoma [Richter syndrome (RS)] is derived from retrospective case series or patients treated on clinical trials. We used the Mayo Clinic CLL Database to identify patients with newly diagnosed CLL between January 2000 and July 2011. Individuals who developed biopsy-proven RS during follow-up were identified. After a median follow-up of 4 years, 37/1641 (2·3%) CLL patients developed RS. The rate of RS was approximately 0·5%/year. Risk of RS was associated with advanced Rai stage at diagnosis (P CLL (1%/year). Stereotyped B-cell receptors (odds-ratio = 4·2; P = 0·01) but not IGHV4-39 family usage was associated with increased risk of RS. Treatment with combination of purine analogues and alkylating agents increased the risk of RS three-fold (odds-ratio = 3·26, P = 0·0003). Median survival after RS diagnosis was 2·1 years. The RS prognosis score stratified patients into three risk groups with median survivals of 0·5 years, 2·1 years and not reached. Both underlying characteristics of the CLL clone and subsequent CLL therapy influence the risk of RS. Survival after RS remains poor and new therapies are needed. © 2013 John Wiley & Sons Ltd.

  2. Does the presence of tumor-induced cortical bone destruction at CT have any prognostic value in newly diagnosed diffuse large B-cell lymphoma?

    Energy Technology Data Exchange (ETDEWEB)

    Adams, Hugo J.A.; Nievelstein, Rutger A.J.; Kwee, Thomas C. [University Medical Center Utrecht, Department of Radiology and Nuclear Medicine, Utrecht (Netherlands); Klerk, John M.H. de [Meander Medical Center, Department of Nuclear Medicine, Amersfoort (Netherlands); Fijnheer, Rob [Meander Medical Center, Department of Hematology, Amersfoort (Netherlands); Heggelman, Ben G.F. [Meander Medical Center, Department of Radiology, Amersfoort (Netherlands); Dubois, Stefan V. [Meander Medical Center, Department of Pathology, Amersfoort (Netherlands)

    2015-05-01

    To determine the prognostic value of tumor-induced cortical bone destruction at computed tomography (CT) in newly diagnosed diffuse large B-cell lymphoma (DLBCL). This retrospective study included 105 patients with newly diagnosed DLBCL who had undergone CT and bone marrow biopsy (BMB) before R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, Oncovin, and prednisolone) chemo-immunotherapy. Cox regression analyses were used to determine the associations of cortical bone status at CT (absence vs. presence of tumor-induced cortical bone destruction), BMB findings (negative vs. positive for lymphomatous involvement), and dichotomized National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) strata (low risk vs. high risk) with progression-free survival (PFS) and overall survival (OS). Univariate Cox regression analysis indicated that cortical bone status at CT was no significant predictor of either PFS or OS (p = 0.358 and p = 0.560, respectively), whereas BMB findings (p = 0.002 and p = 0.013, respectively) and dichotomized NCCN-IPI risk strata (p = 0.002 and p = 0.003, respectively) were significant predictors of both PFS and OS. In the multivariate Cox proportional hazards model, only the dichotomized NCCN-IPI score was an independent predictive factor of PFS and OS (p = 0.004 and p = 0.003, respectively). The presence of tumor-induced cortical bone destruction at CT was not found to have any prognostic implications in newly diagnosed DLBCL. (orig.)

  3. The truncate mutation of Notch2 enhances cell proliferation through activating the NF-κB signal pathway in the diffuse large B-cell lymphomas.

    Directory of Open Access Journals (Sweden)

    Xinxia Zhang

    Full Text Available The Notch2 is a critical membrane receptor for B-cell functions, and also displays various biological roles in lymphoma pathogenesis. In this article, we reported that 3 of 69 (4.3% diffuse large B-cell lymphomas (DLBCLs exhibited a truncate NOTCH2 mutation at the nucleotide 7605 (G/A in the cDNA sequence, which led to partial deletion of the C-terminal of PEST (proline-, glutamic acid-, serine- and threonine-rich domain. The truncate Notch2 activated both the Notch2 and the NF-κB signals and promoted the proliferation of B-cell lymphoma cell lines, including DLBCL and Burkitt's lymphoma cell lines. Moreover, the ectopic proliferation was completely inhibited by ammonium pyrrolidinedithiocarbamate (PDTC, an NF-κB inhibitor. Simultaneously, PDTC also reduced the expression level of Notch2. Based on these results, we conclude that the Notch2 receptor with PEST domain truncation enhances cell proliferation which may be associated with the activation of the Notch2 and the NF-κB signaling. Our results are expected to provide a possible target for new DLBCL therapies by suppressing the Notch2 and the NF-κB signaling.

  4. Dosimetric and Clinical Outcomes With Intensity Modulated Radiation Therapy After Chemotherapy for Patients With Early-Stage Diffuse Large B-cell Lymphoma of Waldeyer Ring

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Yong-Gang; Qi, Shu-Nan; Wang, Shu-Lian; Liu, Yue-Ping; Wang, Wei-Hu; Jin, Jing; Song, Yong-Wen; Ren, Hua; Fang, Hui [Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); He, Xiao-Hui; Dong, Mei [Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Chen, Bo; Lu, Ning-Ning; Li, Ning; Tang, Yuan; Tang, Yu; Dai, Jian-Rong [Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Li, Ye-Xiong, E-mail: yexiong12@163.com [Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China)

    2016-10-01

    Purpose: To assess the dosimetric benefit, prognosis, and toxicity of intensity modulated radiation therapy (IMRT) for early-stage, diffuse large B-cell lymphoma of Waldeyer ring (WR-DLBCL). Methods and Materials: Sixty-one patients with early-stage WR-DLBCL who received chemotherapy followed by IMRT were retrospectively reviewed. Dosimetric parameters for the target volume and critical normal structures were evaluated, and survival was calculated. Linear regression analysis was used to assess the effect of the mean dose (D{sub mean}) to the parotid glands on xerostomia. Results: The median conformity index and homogeneity index of the planning target volume (PTV) were 0.83 and 0.90, respectively, demonstrating very good coverage of the target volume. The mean dose to the parotid glands was 24.9 Gy. The 5-year overall survival (OS), progression-free survival (PFS), and locoregional control (LRC) were 94.7%, 93.1%, and 98.3%, respectively. Early and late toxicities were mild, and no patient experienced late grade ≥3 toxicities. The D{sub mean} to the parotid glands had a linear correlation with late grade ≥2 xerostomia. Conclusions: IMRT after chemotherapy can provide excellent dose conformity and achieve favorable survival and LRC with mild toxicities in patients with early-stage WR-DLBCL. Dose constraints for the parotid glands should be limited to <24 Gy for early-stage WR-DLBCL.

  5. A clinically based prognostic index for diffuse large B-cell lymphoma with a cut-off at 70 years of age significantly improves prognostic stratification

    DEFF Research Database (Denmark)

    Gang, Anne O.; Pedersen, Michael; d'Amore, Francesco

    2015-01-01

    The introduction of rituximab and generally improved health among elderly patients have increased the survival of patients with diffuse large B-cell lymphoma (DLBCL). The International Prognostic Index (IPI) from 1992 is based on pre-rituximab data from clinical trials including several lymphoma ...... dehydrogenase (LDH), stage and albumin level, and (2) a separate age-adjusted DLBCL-PI for patients 1 extranodal lesion, however excluding stage....... subtypes. We applied IPI factors to a population-based rituximab-treated cohort of 1990 patients diagnosed 2000-2010 and explored new factors and the optimal prognostic age cut-off for DLBCL. Multivariate-analyses (MVA) confirmed the prognostic value of all IPI factors except the presence of > 1 extranodal...... lesion. The optimal age cut-off was 70 years. In a MVA of albumin, lymphocyte count, sex, immunoglobulin G, bulky disease, hemoglobin and B-symptoms, only albumin was prognostic. We propose: (1) a modified DLBCL prognostic index (DLBCL-PI) including: age (70 years), performance status (PS), lactate...

  6. Significance of tumor size and radiation dose to local control in stage I-III diffuse large cell lymphoma treated with CHOP-Bleo and radiation

    International Nuclear Information System (INIS)

    Fuller, Lillian M.; Krasin, Matthew J.; Velasquez, William S.; Allen, Pamela K.; McLaughlin, Peter; Rodriguez, M. Alma; Hagemeister, Fredrick B.; Swan, Forrest; Cabanillas, Fernando; Palmer, Judy L.; Cox, James D.

    1995-01-01

    Purpose: The purpose of this study was to evaluate the possible effect of adjunctive involved field (IF) radiotherapy on long-term local control for patients with Ann Arbor Stage I-III diffuse large cell lymphoma (DLCL) who achieved a complete remission on a combined modality program which included cyclophosphamide, doxorubicin, vincristine, prednisone, and Bleomycin (CHOP-Bleo). Methods and Materials: One hundred and ninety patients with Ann Arbor Stage I-III DLCL were treated with CHOP-Bleo and radiotherapy. Analyses were undertaken to determine (a) response to treatment according to stage, extent of maximum local disease, and irradiation dose either < 40 Gy or ≥ 40 Gy and (b) relapse patterns. Results: A complete remission (CR) was achieved in 162 patients. Among patients who achieved a CR, local control was better for those who received tumor doses of ≥ 40 Gy (97%) than for those who received < 40 Gy (83%) (p = 0.002.) Among those with extensive local disease, the corresponding control rates were 88% and 71%, respectively. A study of distant relapse patterns following a CR showed that the first relapse usually involved an extranodal site. Conclusion: Radiotherapy was an effective adjunctive treatment to CHOP-Bleo for patients with stage I-III DLCL who achieved a CR. Patterns of relapse suggested that total nodal irradiation (TNI) possibly could have benefited a small subset of patients

  7. Lenalidomide combined with R-GDP in a patient with refractory CD5-positive diffuse large B-cell lymphoma: A promising response and review.

    Science.gov (United States)

    Zhang, Yaping; Wang, Xinfeng; Liu, Yifei; Sun, Chunfeng; Shi, Wenyu; Huang, Hongming

    2018-07-03

    CD5-positive (CD5+) diffuse large B-cell lymphoma (DLBCL) is associated with poor survival compared with CD5-negative DLBCL. The clinical characteristics of CD5+ DLBCL are different from both CD5-negative DLBCL and other CD5+ B cell lymphomas. There is currently no promising chemotherapy for CD5+ DLBCL. Herein, we report a 49-year-old Asian male with refractory CD5+ DLBCL. He complained of aggravated abdominal pain and weight loss. Computed tomography scan revealed abdominal masses, widespread lymphadenopathy, splenomegaly, and intussusception of the ileocecal junction with bowel wall thickening. Core needle aspiration biopsy of an abdominal mass was performed and immunohistochemistry revealed DLBCL of nongerminal center type. In this report, the dose-intensified R-Hyper CVAD (A) regimen as salvage therapy was introduced but failed to result in substantial improvement over the initially standard R-CHOP regimen. Next, the R-GDP regimen was administered as second-line treatment, but only resulted in a partial response. However, the addition of lenalidomide to R-GDP (R2-GDP) resulted in complete remission. The clinical features, pathogenesis, and possible mechanism of action of lenalidomide in CD5+ DLBCL have been described in the literature. The results of the present case report and literature searches indicate that CD5+ DLBCL may share a common pathway with activated B-cell like (ABC) DLBCL as determined by gene expression profiling. Lenalidomide is expected to induce favorable responses in patients with CD5+ DLBCL.

  8. Gemcitabine, dexamethasone, and cisplatin (GDP) is an effective and well-tolerated salvage therapy for relapsed/refractory diffuse large B-cell lymphoma and Hodgkin lymphoma.

    Science.gov (United States)

    Moccia, Alden A; Hitz, Felicitas; Hoskins, Paul; Klasa, Richard; Power, Maryse M; Savage, Kerry J; Shenkier, Tamara; Shepherd, John D; Slack, Graham W; Song, Kevin W; Gascoyne, Randy D; Connors, Joseph M; Sehn, Laurie H

    2017-02-01

    The optimal choice of salvage therapy for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) or Hodgkin lymphoma (HL) remains unknown. Based on promising results of phase II trials, the preferred salvage regimen in British Columbia since 2002 has been the out-patient regimen, gemcitabine, dexamethasone, and cisplatin (GDP). We conducted a retrospective analysis including all patients with relapsed/refractory DLBCL or HL who received GDP as salvage therapy between September 2002 and June 2010. We identified 235 patients: 152 DLBCL, 83 HL. Overall response rates were 49% and 71% for patients with DLBCL and HL, respectively. Within the transplant-eligible population, 52% of patients with DLBCL and 96% of patients with HL proceeded to stem cell transplantation. The 2-year progression-free survival and overall survival were 21% and 28% in the DLBCL cohort, and 58% and 85% in the HL group. GDP is an effective and well-tolerated out-patient salvage regimen for relapsed/refractory DLBCL and HL.

  9. IMPACT OF PRE-TRANSPLANT RITUXIMAB ON SURVIVAL AFTER AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR DIFFUSE LARGE B-CELL LYMPHOMA

    Science.gov (United States)

    Fenske, Timothy S.; Hari, Parameswaran N.; Carreras, Jeanette; Zhang, Mei-Jie; Kamble, Rammurti T.; Bolwell, Brian J.; Cairo, Mitchell S.; Champlin, Richard E.; Chen, Yi-Bin; Freytes, César O.; Gale, Robert Peter; Hale, Gregory A.; Ilhan, Osman; Khoury, H. Jean; Lister, John; Maharaj, Dipnarine; Marks, David I.; Munker, Reinhold; Pecora, Andrew L.; Rowlings, Philip A.; Shea, Thomas C.; Stiff, Patrick; Wiernik, Peter H.; Winter, Jane N.; Rizzo, J. Douglas; van Besien, Koen; Lazarus, Hillard M.; Vose, Julie M.

    2010-01-01

    Incorporation of the anti-CD20 monoclonal antibody rituximab into front-line regimens for diffuse large B-cell lymphoma (DLBCL) has resulted in improved survival. Despite this progress, many patients develop refractory or recurrent DLBCL and then receive autologous hematopoietic stem cell transplantation (AuHCT). It is unclear to what extent pre-transplant exposure to rituximab affects outcomes following AuHCT. Outcomes of 994 patients receiving AuHCT for DLBCL between 1996 and 2003 were analyzed according to whether rituximab was (n=176, “+R” group) or was not (n=818, “ −R” group) administered with front-line or salvage therapy prior to AuHCT. The +R group had superior progression-free survival (50% versus 38%, p=0.008) and overall survival (57% versus 45%, p=0.006) at 3 years. Platelet and neutrophil engraftment were not affected by exposure to rituximab. Non-relapse mortality (NRM) did not differ significantly between the +R and −R groups. In multivariate analysis, the +R group had improved progression-free survival (relative risk of relapse/progression or death 0.64, p<0.001) and improved overall survival (relative risk of death of 0.74, p=0.039). We conclude that pre-transplant rituximab is associated with a lower rate of progression and improved survival following AuHCT for DLBCL, with no evidence of impaired engraftment or increased NRM. PMID:19822306

  10. The Glasgow Prognostic Score as a significant predictor of diffuse large B cell lymphoma treated with R-CHOP in China.

    Science.gov (United States)

    Li, Xiaoyang; Zhang, Yunxiang; Zhao, Weili; Liu, Zhao; Shen, Yang; Li, Junmin; Shen, Zhixiang

    2015-01-01

    The Glasgow Prognostic Score (GPS) incorporates C-reactive protein and albumin as clinically useful markers of tumor behavior and shows significant prognostic value in several types of solid tumors. The accuracy of the GPS in predicting outcomes in diffuse large B cell lymphoma (DLBCL) remains unknown. We performed this study to evaluate the prognostic significance of the GPS in DLBCL in China. We retrospectively analyzed 160 patients with newly diagnosed DLBCL at the Shanghai Ruijin Hospital (China). The prognostic value of the GPS was evaluated and compared with that of the International Prognostic Index (IPI) and immunohistochemical subtyping. The GPS was defined as follows: GPS-0, C-reactive protein (CRP) ≤10 mg/L and albumin ≥35 g/L; GPS-1, CRP >10 mg/L or albumin L; and GPS-2, CRP >10 mg/L and albumin L. Patients with lower GPS tended to have better outcomes including progression-free survival (PFS, P GPS and high IPI score were independent adverse predictors of OS. Similar to several other tumors, GPS is a reliable predictor of survival outcomes in DLBCL patients treated with R-CHOP therapy. Inflammatory responses are implicated in the progression and survival of patients with DLBCL.

  11. Y-box-binding protein-1 (YB-1) promotes cell proliferation, adhesion and drug resistance in diffuse large B-cell lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Miao, Xiaobing; Wu, Yaxun [Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong 226361, Jiangsu (China); Wang, Yuchan [Department of Pathogen, Medical College, Nantong University, Nantong 226001, Jiangsu (China); Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226001, Jiangsu (China); Zhu, Xinghua; Yin, Haibing [Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong 226361, Jiangsu (China); He, Yunhua [Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226001, Jiangsu (China); Li, Chunsun; Liu, Yushan; Lu, Xiaoyun; Chen, Yali; Shen, Rong [Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong 226361, Jiangsu (China); Xu, Xiaohong, E-mail: xuxiaohongnantong@126.com [Department of Oncology, Affiliated Cancer Hospital of Nantong University, Nantong 226361, Jiangsu (China); He, Song, E-mail: hesongnt@126.com [Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong 226361, Jiangsu (China)

    2016-08-15

    YB-1 is a multifunctional protein, which has been shown to correlate with resistance to treatment of various tumor types. This study investigated the expression and biologic function of YB-1 in diffuse large B-cell lymphoma (DLBCL). Immunohistochemical analysis showed that the expression statuses of YB-1 and pYB-1{sup S102} were reversely correlated with the clinical outcomes of DLBCL patients. In addition, we found that YB-1 could promote the proliferation of DLBCL cells by accelerating the G1/S transition. Ectopic expression of YB-1 could markedly increase the expression of cell cycle regulators cyclin D1 and cyclin E. Furthermore, we found that adhesion of DLBCL cells to fibronectin (FN) could increase YB-1 phosphorylation at Ser102 and pYB-1{sup S102} nuclear translocation. In addition, overexpression of YB-1 could increase the adhesion of DLBCL cells to FN. Intriguingly, we found that YB-1 overexpression could confer drug resistance through cell-adhesion dependent and independent mechanisms in DLBCL. Silencing of YB-1 could sensitize DLBCL cells to mitoxantrone and overcome cell adhesion-mediated drug resistance (CAM-DR) phenotype in an AKT-dependent manner. - Highlights: • The expression statuses of YB-1 and pYB-1{sup S102} are reversely correlated with outcomes of DLBCL patients. • YB-1 promotes cell proliferation by accelerating G1/S transition in DLBCL. • YB-1 confers drug resistance to mitoxantrone in DLBCL.

  12. Second-line therapy in diffuse large B-cell lymphoma (DLBCL): treatment patterns and outcomes in older patients receiving outpatient chemotherapy.

    Science.gov (United States)

    Danese, Mark D; Griffiths, Robert I; Gleeson, Michelle L; Dalvi, Tapashi; Li, Jingyi; Mikhael, Joseph R; Deeter, Robert; Dreyling, Martin

    2017-05-01

    Using SEER-Medicare linked data we identified elderly patients diagnosed with diffuse large B-cell lymphoma (DLBCL) between January 2000 and December 2007 who received second-line outpatient chemotherapy for relapsed or refractory disease. Second-line regimens were classified into three mutually exclusive groups: aggressive, conventional, and palliative. Of the 632 (426 relapsed, 206 refractory) patients in the cohort, 27.8% received aggressive second-line therapy, 39.1% received conventional therapy, and 33.1% received palliative therapy. There were no differences in survival by type of therapy received, either for relapsed or refractory patients, although the patient risk profile differed significantly. However, duration of remission, male gender, and anemia at diagnosis were important predictors in relapsed patients, and male gender, B-symptoms, comorbidity burden, and poverty status were important predictors in refractory patients. Survival in elderly patients receiving second-line therapy remains poor, and the 24-month cost of all care exceeds $97,000. Patients would benefit from improved treatment options.

  13. Patients with primary diffuse large B-cell lymphoma of female genital tract have high risk of central nervous system relapse.

    Science.gov (United States)

    Cao, Xin-xin; Li, Jian; Zhang, Wei; Duan, Ming-hui; Shen, Ti; Zhou, Dao-bin

    2014-06-01

    The objective of this study was to evaluate retrospectively the clinical characteristics, treatments, and outcomes of patients with primary diffuse large B-cell lymphoma (DLBCL) of the female genital tract. The basic characteristics, treatments, and outcomes of six patients diagnosed with primary DLBCL of the female genital tract, including the ovary, uterine cervix, and vagina, treated in our hospital between 2000 and 2012, were analyzed retrospectively. Seven of 323 (2.2 %) newly diagnosed DLBCLs were diagnosed as primary female genital tract DLBCL. Six patients with complete medical data were included in the analysis. The median age at diagnosis was 52.5 years (range 20-65). The presenting symptoms included abnormal vaginal bleeding, increased vaginal discharge, abdominal fullness, and abdominal pain. Two patients had stage IE disease and four patients had stage IIE disease. Treatment included chemotherapy only in five patients, and combined chemotherapy and localized radiation in one patient. After a median follow-up of 58 months, four patients showed relapse in the central nervous system and two had died from progressive disease. The median progression-free survival was 27 months and the median overall survival for this group has not been reached. Patients with primary female genital tract DLBCL may have poor outcomes and a high risk of central nervous system relapse. Central nervous system prophylaxis might be considered in addition to systemic chemotherapy for DLBCL of the female genital tract.

  14. Multiplex polymerase chain reaction-based prognostic models in diffuse large B-cell lymphoma patients treated with R-CHOP

    DEFF Research Database (Denmark)

    Green, Tina M; Jensen, Andreas K; Holst, René

    2016-01-01

    We present a multiplex analysis for genes known to have prognostic value in an attempt to design a clinically useful classification model in patients with diffuse large B-cell lymphoma (DLBCL). Real-time polymerase chain reaction was used to measure transcript levels of 28 relevant genes in 194 de...... models. The best model was validated in data from an online available R-CHOP treated cohort. With progression-free survival (PFS) as primary endpoint, the best performing IPI independent model incorporated the LMO2 and HLADQA1 as well as gene interactions for GCSAMxMIB1, GCSAMxCTGF and FOXP1xPDE4B....... This model assigned 33% of patients (n = 60) to poor outcome with an estimated 3-year PFS of 40% vs. 87% for low risk (n = 61) and intermediate (n = 60) risk groups (P model incorporated LMO2 and BCL2 and assigned 33% of the patients with a 3-year PFS of 35% vs...

  15. How breast cancer chemotherapy increases the risk of leukemia: Thoughts about a case of diffuse large B-cell lymphoma and leukemia after breast cancer chemotherapy.

    Science.gov (United States)

    Zhang, Bin; Zhang, Xia; Li, Minghuan; Kong, Li; Deng, Xiaoqin; Yu, Jinming

    2016-01-01

    The latest studies suggest that prophylactic chemotherapy or adjuvant chemotherapy for early stage breast cancer may increase the leukemia risk in patients. For patients with a low risk for breast cancer recurrence, physicians who make the choice for adjuvant therapy should consider the risk of its long-term side effects. Is the occurrence of lymphatic system cancer and leukemia after breast cancer treatment associated with chemotherapy? Can these types of leukemia be classified as therapy-related leukaemias? We believe that there may be correlations between any diseases, butwe cannot rush to conclusions or dismiss a correlation because we understand little about the diseases themselves.In this paper, we present a case of secondary diffuse large B-cell lymphoma and leukemia in patients after breast cancer chemotherapy, it is undeniable that this is a special event. For two distinct tumouroccurrences at different times, we cannot give a clear explanation because of thechanges in the genes that might link them together and we hope to attract the attention of other clinicians.

  16. [Use of archival formalin-fixed, paraffin-embedded (FFPE) tissue samples for molecular genetic analysis in diffuse large B-cell lymphoma (DLBCL)].

    Science.gov (United States)

    Jarošová, Marie; Kučerová, Jana; Flodr, Patrik; Mikešová, Michaela; Procházka, Vít; Papajík, Tomáš

    2014-04-01

    The currently valid molecular genetic subclassification of patients with diffuse large B-cell lymphoma (DLBCL) into three prognostic subgroups based on expression profiling has been the objective of numerous genetic studies. In routine clinical practice, however, expression profiling technology remains unavailable for the most of centers. Apart from the technology, in some cases molecular genetic laboratories have problems obtaining high-quality material, i.e. fresh tissues, for RNA isolation to determine gene expression. One possibility is to determine the gene expression from RNA obtained by isolation from formalin-fixed, paraffin-embedded (FFPE) tissue. This pilot study aimed at isolating RNA from FFPE in patients diagnosed with DLBCL and verifying the potential use of such RNA for the expression analysis of 7 selected genes. Although the study showed that it is possible to isolate RNA and determine the expression of the selected genes from archival material, the values of relative expression of some genes in the set were too variable to be used for unambiguous prognostic classification. It was confirmed that retrospective analyses of selected genes may be performed with sufficient material obtained, and that properly archived blocks may be used for molecular biology analyses even after 8 years.

  17. Therapeutic strategy with artificially-designed i-lncRNA targeting multiple oncogenic microRNAs exhibits effective antitumor activity in diffuse large B-cell lymphoma.

    Science.gov (United States)

    Su, Yinghan; Sun, Bin; Lin, Xuejing; Zhao, Xinying; Ji, Weidan; He, Miaoxia; Qian, Haihua; Song, Xianmin; Yang, Jianmin; Wang, Jianmin; Chen, Jie

    2016-08-02

    In diffuse large B-cell lymphoma (DLBCL), many oncogenic microRNAs (OncomiRs) are highly expressed to promote disease development and progression by inhibiting the expression and function of certain tumor suppressor genes, and these OncomiRs comprise a promising new class of molecular targets for the treatment of DLBCL. However, most current therapeutic studies have focused on a single miRNA, with limited treatment outcomes. In this study, we generated tandem sequences of 10 copies of the complementary binding sequences to 13 OncomiRs and synthesized an interfering long non-coding RNA (i-lncRNA). The highly-expressed i-lncRNA in DLBCL cells would compete with the corresponding mRNAs of OncomiR target genes for binding OncomiRs, thereby effectively consuming a large amount of OncomiRs and protecting many tumor suppressor genes. The in vitro experiments confirmed that the i-lncRNA expression significantly inhibited cell proliferation, induced cell cycle arrest and apoptosis in DLBCL cell lines, mainly through upregulating the expression of PTEN, p27kip1, TIMP3, RECK and downregulating the expression of p38/MAPK, survivin, CDK4, c-myc. In the established SUDHL-4 xenografts in nude mice, the treatment strategy involving adenovirus-mediated i-lncRNA expression significantly inhibited the growth of DLBCL xenografts. Therefore, this treatment would specifically target the carcinogenic effects of many OncomiRs that are usually expressed in DLBCL and not in normal cells, such a strategy could improve anti-tumor efficacy and safety and may be a good prospect for clinical applications.

  18. Diffuse γ-ray emission observed by the Fermi large area telescope: massive stars, cosmic rays and the census of the interstellar medium in the galaxy

    International Nuclear Information System (INIS)

    Tibaldo, L.

    2011-01-01

    Galactic diffuse γ-ray emission is produced by interactions of cosmic rays (CRs) with interstellar gas and low-energy radiation fields. This is the brightest component of the high-energy γ-ray sky, surveyed since 2008 with unprecedented sensitivity and angular resolution by the Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope. Galactic diffuse emission constitutes not only a bright and structured background which needs to be modeled in order to study individual sources and fainter diffuse components, but it can be used also as a probe of the interstellar environment of the Milky Way. We present in-depth studies of LAT γ-ray observations of selected regions in the local and outer Galaxy. LAT data are compared with multiwavelength tracers of the interstellar medium (ISM), including radio/mm-wave lines of gas and infrared emission/extinction from dust. The impact of the HI optical depth, often overlooked in the past, is carefully examined and recognized currently as the dominant source of uncertainty in the interpretation of observations. On one hand, we discuss the constraints provided by the γ-ray data on the census of the interstellar gas. We determine the X C O = N(H 2 )/W C O ratio for several clouds, finding no significant gradients in the Galactic disc over a range of ∼ 3.5 kpc in Galactocentric radius, and variations of a factor ≤ 2 in nearby local clouds. We also find evidence for an ubiquitous dark phase of interstellar gas which does not shine at radio/mm wavelengths and which provides a mass ∼ 50% of that traced by CO. For the first time we determine its γ-ray spectrum which is found to be well correlated with that of HI, thus further confirming that the emission originates from interstellar gas. On the other hand, we use the emissivity per hydrogen atom to infer the distribution of CRs in distant locations not accessible by direct measurements. While the local HI emissivity is consistent with the CR spectra measured near

  19. Clinical features, tumor biology, and prognosis associated with MYC rearrangement and Myc overexpression in diffuse large B-cell lymphoma patients treated with rituximab-CHOP

    DEFF Research Database (Denmark)

    Xu-Monette, Zijun Y; Dabaja, Bouthaina S; Wang, Xiaoxiao

    2015-01-01

    MYC dysregulation, including MYC gene rearrangement and Myc protein overexpression, is of increasing clinical importance in diffuse large B-cell lymphoma (DLBCL). However, the roles of MYC and the relative importance of rearrangement vs overexpression remain to be refined. Gaining knowledge about...

  20. Patients with diffuse large B-cell lymphoma of germinal center origin with BCL2 translocations have poor outcome, irrespective of MYC status: a report from an International DLBCL rituximab-CHOP Consortium Program Study.

    NARCIS (Netherlands)

    Visco, C.; Tzankov, A.; Xu-Monette, Z.Y.; Miranda, R.N.; Tai, Y.C.; Li, Y.; Liu, W.M.; d'Amore, E.S.; Li, Y.O.; Montes-Moreno, S.; Dybkaer, K.; Chiu, A.; Orazi, A.; Zu, Y.; Bhagat, G.; Wang, H.Y.; Dunphy, C.H.; His, E.D.; Zhao, X.F.; Choi, W.W.; Krieken, J.H.J.M. van; Huang, Q.; Ai, W.; O'Neill, S.; Ponzoni, M.; Ferreri, A.J.; Kahl, B.S.; Winter, J.N.; Go, R.S.; Dirnhofer, S.; Piris, M.A.; Moller, M.B.; Wu, L.; Medeiros, L.J.; Young, K.H.

    2013-01-01

    Diffuse large B-cell lymphoma can be classified by gene expression profiling into germinal center and activated B-cell subtypes with different prognoses after rituximab-CHOP. The importance of previously recognized prognostic markers, such as Bcl-2 protein expression and BCL2 gene abnormalities, has

  1. MYC/BCL2 protein coexpression contributes to the inferior survival of activated B-cell subtype of diffuse large B-cell lymphoma and demonstrates high-risk gene expression signatures

    DEFF Research Database (Denmark)

    Hu, Shimin; Xu-Monette, Zijun Y; Tzankov, Alexander

    2013-01-01

    Diffuse large B-cell lymphoma (DLBCL) is stratified into prognostically favorable germinal center B-cell (GCB)-like and unfavorable activated B-cell (ABC)-like subtypes based on gene expression signatures. In this study, we analyzed 893 de novo DLBCL patients treated with R-CHOP (rituximab, cyclo...

  2. Linfoma Difuso de Grandes Células  de Intestino Delgado: Relato de Caso Diffuse Large -Cell Lymphoma of Small Bowel: Case Report

    Directory of Open Access Journals (Sweden)

    Gustavo Nunes Medina Coeli

    2012-06-01

    are subtype B cell. Case Report: It´s presented a case of rare small bowel lymphoma in a female patient of 77 years who sought medical care with nonspecific symptoms and an anemic framework. Radiological examinations were essential for diagnosis for diagnostic enlightenment and propaedeutics. Tumor markers were negative and the inflamatorious tests activities were positives. In hospitalization, the patient had an abrupt worsening in her clinic picture, needing a surgery. During the operation was identified in the proximal jejunum a perfurative damage with an ulcerated aspect with ulcers, adhesions in the bladder and in fundus of the uterus. The patient did not evaluated well and died after three days. The pathology confirmed a diffuse No Hodgkin lymphoma of Large B-cells with a high rate of cell proliferation. Discussion: The preoperative radiological diagnosis of tumor of the small intestine is only obtained in a small percentage of symptomatic patients. Imaging studies show infiltrative, polypoid, or aneurysmatic morphologicals types .Usually occurs circumferential involvement of the handle, with irregular thickening of the folds of variable length. Conclusion: The intent of this study is to document a rare tumor of the small bowel Non-Hodgkin Lymphoma Diffuse Large B-Cell type, multicentric, that was difficult to diagnose and with a rapid evolution of symptoms, which resulted in acute intestinal obstruction, requiring emergency surgery.

  3. Prognostic significances of overexpression MYC and/or BCL2 in R-CHOP-treated diffuse large B-cell lymphoma: A Systematic review and meta-analysis.

    Science.gov (United States)

    Li, Lu; Li, Yanyan; Que, Ximei; Gao, Xue; Gao, Qian; Yu, Mingxing; Ma, Kaili; Xi, Yanfeng; Wang, Tong

    2018-04-19

    Numerous studies have investigated the prognostic values of MYC and/or BCL2 protein overexpression in diffuse large B-cell lymphoma (DLBCL). However, the results still demonstrate discrepancies among different studies. We aimed to do a systematic review and meta-analysis on the relationships between overexpression MYC and/or BCL2 and DLBCLs treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). This study followed the guidelines of PRISMA and Cochrane handbook. The hazard ratios (HRs) for overall survival (OS) were pooled to estimate the main effect size. Twenty studies recruited a total of 5576 patients were available for this meta-analysis. The results showed that MYC (HR = 1.96, 95%CI (confidence interval) = 1.69-2.27)without heterogeneity(I 2  = 17.2%, P = 0.280), BCL2 (HR = 1.65, 95%CI = 1.43-1.89, I 2  = 20.7%, P = 0.234) protein overexpression, and co-overexpression (HR = 2.58, 95%CI = 2.19-3.04, I 2  = 17.2%, P = 0.275) had a poor prognosis in R-CHOP treated DLBCL patients, respectively. The current analysis indicated that MYC and/or BCL2 protein overexpression, and particularly co-overexpression was related to short overall survival in R-CHOP treated DLBCL patients, showing that application of the two new biomarkers can help to better stratify DLBCL patients and guide targeted treatment.

  4. The rGel/BLyS Fusion Toxin Inhibits Diffuse Large B-cell Lymphoma Growth In Vitro and In Vivo

    Directory of Open Access Journals (Sweden)

    Mi-Ae Lyu

    2010-05-01

    Full Text Available Diffuse large B-cell lymphoma (DLBCL is an aggressive subtype of B-cell non-Hodgkin lymphoma (NHL and accounts for 30%to 40%of NHL. Molecules targeting nuclear factor-κB (NF-κB are expected to be of therapeutic value in those tumors where NF-κB seems to play a unique survival role such as activated B-cell (ABC-subtype DLBCL. We previously generated a rGel/BLyS fusion toxin for receptor-mediated delivery of the rGel toxin specifically to malignant B cells. In this study, we examined this fusion toxin for its ability to suppress DLBCL growth in vitro and in vivo. rGel/BLyS was specifically cytotoxic to DLBCL lines expressing all three BLyS receptors and constitutively active NF-κB. Treatment with rGel/BLyS induced down-regulation of the phosphorylation of inhibitory subunit of NF-κB (IκB-α, inhibition of NF-κB DNA-binding activity, and accumulation of IκB-α. In agreement with these results, we additionally found that rGel/BLyS downregulated levels of several NF-κB targets including Bcl-xL, Mcl-1, survivin, and x-chromosome linked inhibitor-of-apoptosis. Treatment also induced up-regulation of Bax and apoptosis through caspase-3 activation and poly ADP-ribose polymerase cleavage. Importantly, rGel/BLyS significantly inhibited tumor growth (P < .05 in a DLBCL xenograft model. Thus, our results indicate that rGel/BLyS is an excellent candidate for the treatment of aggressive NHLs that are both dependent on NF-κB and are resistant to conventional chemotherapeutic regimens.

  5. Loss of function mutations in PTPN6 promote STAT3 deregulation via JAK3 kinase in diffuse large B-cell lymphoma

    Science.gov (United States)

    Demosthenous, Christos; Han, Jing Jing; Hu, Guangzhen; Stenson, Mary; Gupta, Mamta

    2015-01-01

    PTPN6 (SHP1) is a tyrosine phosphatase that negatively controls the activity of multiple signaling pathways including STAT signaling, however role of mutated PTPN6 is not much known. Here we investigated whether PTPN6 might also be a potential target for diffuse large B cell lymphoma (DLBCL) and performed Sanger sequencing of the PTPN6 gene. We have identified missense mutations within PTPN6 (N225K and A550V) in 5% (2/38) of DLBCL tumors. Site directed mutagenesis was performed to mutate wild type (WT) PTPN6 and stable cell lines were generated by lentiviral transduction of PTPN6WT, PTPN6N225K and PTPN6A550V constructs, and effects of WT or mutated PTPN6 on STAT3 signaling were analyzed. WT PTPN6 dephosphorylated STAT3, but had no effect on STAT1, STAT5 or STAT6 phosphorylation. Both PTPN6 mutants were unable to inhibit constitutive, as well as cytokines induced STAT3 activation. Both PTPN6 mutants also demonstrated reduced tyrosine phosphatase activity and exhibited enhanced STAT3 transactivation activity. Intriguingly, a lack of direct binding between STAT3 and WT or mutated PTPN6 was observed. However, compared to WT PTPN6, cells expressing PTPN6 mutants exhibited increased binding between JAK3 and PTPN6 suggesting a more dynamic interaction of PTPN6 with upstream regulators of STAT3. Consistent with this notion, both the mutants demonstrated increased resistance to JAK3 inhibitor, WHIP-154 relative to WT PTPN6. Overall, this is the first study, which demonstrates that N225K and A550V PTPN6 mutations cause loss-of-function leading to JAK3 mediated deregulation of STAT3 pathway and uncovers a mechanism that tumor cells can use to control PTPN6 substrate specificity. PMID:26565811

  6. Expression of Myc, but not pSTAT3, is an adverse prognostic factor for diffuse large B-cell lymphoma treated with epratuzumab/R-CHOP.

    Science.gov (United States)

    Gupta, Mamta; Maurer, Matthew J; Wellik, Linda E; Law, Mark E; Han, Jing Jing; Ozsan, Nazan; Micallef, Ivana N; Dogan, Ahmet; Witzig, Thomas E

    2012-11-22

    STAT3 regulates cell growth by up-regulating downstream targets, such as Myc. The frequency of phosphorylated STAT3 (pSTAT3) and Myc expression and their prognostic relevance is unknown within diffuse large B-cell lymphoma (DLBCL) germinal center B-cell (GCB) and non-GCB subtypes. pSTAT3 and Myc were studied by immunohistochemistry (IHC) on tumors from 40 DLBCL patients uniformly treated on a clinical trial of epratuzumab/rituximab-CHOP. A total of 35% of cases were pSTAT3-positive, and pSTAT3 positivity was more frequent in the non-GCB (P = .06) type but did not correlate with event-free survival (EFS). Myc expression was observed in 50% of cases and was more frequent in non-GCB type (P = .07). Myc-positive cases had inferior EFS in all patients, including the GCB and pSTAT3-positive cases, were more likely to express Myc (P = .06). Myc translocations involving the major breakpoint regions were found in 10% (3 of 29) of cases, and all 3 cases were GCB and had an inferior EFS (P = .09). pSTAT3, but not Myc expression, was correlated with elevated pretreatment serum cytokines, such as IL-10 (P = .05), G-CSF (P = .03), and TNF-α (P = .04). pSTAT3 IHC in DLBCL tumors has the potential to identify patients for STAT3 pathway-directed therapy; Myc IHC is a potential marker for inferior EFS in GCB patients.

  7. Cancer-specific mortality, cure fraction, and noncancer causes of death among diffuse large B-cell lymphoma patients in the immunochemotherapy era.

    Science.gov (United States)

    Howlader, Nadia; Mariotto, Angela B; Besson, Caroline; Suneja, Gita; Robien, Kim; Younes, Naji; Engels, Eric A

    2017-09-01

    Survival after the diagnosis of diffuse large B-cell lymphoma (DLBCL) has been increasing since 2002 because of improved therapies; however, long-term outcomes for these patients in the modern treatment era are still unknown. Using Surveillance, Epidemiology, and End Results data, this study first assessed factors associated with DLBCL-specific mortality during 2002-2012. An epidemiologic risk profile, based on clinical and demographic characteristics, was used to stratify DLBCL cases into low-, medium-, and high-risk groups. The proportions of DLBCL cases that might be considered cured in these 3 risk groups was estimated. Risks of death due to various noncancer causes among DLBCL cases versus the general population were also calculated with standardized mortality ratios (SMRs). Overall, 8274 deaths were recorded among 18,047 DLBCL cases; 76% of the total deaths were attributed to DLBCL, and 24% were attributed to noncancer causes. The 10-year survival rates for the low-, medium-, and high-risk groups were 80%, 60%, and 36%, respectively. The estimated cure proportions for the low-, medium-, and high-risk groups were 73%, 49%, and 27%, respectively; however, these cure estimates were uncertain because of the need to extrapolate the survival curves beyond the follow-up time. Mortality risks calculated with SMRs were elevated for conditions including vascular diseases (SMR, 1.3), infections (SMR, 3.1), gastrointestinal diseases (SMR, 2.5), and blood diseases (SMR, 4.6). These mortality risks were especially high within the initial 5 years after the diagnosis and declined after 5 years. Some DLBCL patients may be cured of their cancer, but they continue to experience excess mortality from lymphoma and other noncancer causes. Cancer 2017;123:3326-34. © 2017 American Cancer Society. © 2017 American Cancer Society.

  8. P38 MAPK expression and activation predicts failure of response to CHOP in patients with Diffuse Large B-Cell Lymphoma

    International Nuclear Information System (INIS)

    Vega, Gabriel G.; Avilés-Salas, Alejandro; Chalapud, J. Ramón; Martinez-Paniagua, Melisa; Pelayo, Rosana; Mayani, Héctor; Hernandez-Pando, Rogelio; Martinez-Maza, Otoniel; Huerta-Yepez, Sara; Bonavida, Benjamin; Vega, Mario I.

    2015-01-01

    The p38 MAPK is constitutively activated in B-NHL cell lines and regulates chemoresistance. Accordingly, we hypothesized that activated p38 MAPK may be associated with the in vivo unresponsiveness to chemotherapy in B-NHL patients. Tissue microarrays generated from eighty untreated patients with Diffused Large B Cell Lymphoma (DLBCL) were examined by immunohistochemistry for the expression of p38 and phospho p38 (p-p38) MAPK. In addition, both Bcl-2 and NF-κB expressions were determined. Kaplan Meier analysis was assessed. Tumor tissues expressed p38 MAPK (82 %) and p-p38 MAPK (30 %). Both p38 and p-p38 MAPK expressions correlated with the high score performance status. A significant correlation was found between the expression p-p38 and poor response to CHOP. The five year median follow-up FFS was 81 % for p38 − and 34 % for p38 + and for OS was 83 % for p38 − and 47 % for p38 + . The p-p38 + tissues expressed Bcl-2 and 90 % of p-p38 − where Bcl-2 − . The coexpression of p-p38 and Bcl-2 correlated with pool EFS and OS. There was no correlation between the expression of p-p38 and the expression of NF-κB. The findings revealed, for the first time, that a subset of patients with DLBCL and whose tumors expressed high p-p38 MAPK responded poorly to CHOP therapy and had poor EFS and OS. The expression of p38, p-p38, Bcl2 and the ABC subtype are significant risk factors both p38 and p-p38 expressions remain independent prognostic factors. The online version of this article (doi:10.1186/s12885-015-1778-8) contains supplementary material, which is available to authorized users

  9. Brain glucose metabolism in diffuse large B-cell lymphoma patients as assessed with FDG-PET: impact on outcome and chemotherapy effects.

    Science.gov (United States)

    Adams, Hugo Ja; de Klerk, John Mh; Fijnheer, Rob; Heggelman, Ben Gf; Dubois, Stefan V; Nievelstein, Rutger Aj; Kwee, Thomas C

    2016-06-01

    There is a lack of data on the effect of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy on brain glucose metabolism of diffuse large B-cell lymphoma (DLBCL) patients, as measured by 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET). Moreover, the prognostic value of brain glucose metabolism measurements is currently unknown. To investigate the use of FDG-PET for measurement of brain glucose metabolism in R-CHOP-treated DLBCL patients, and to assess its prognostic value. This retrospective study included DLBCL patients who underwent FDG-PET including the brain. FDG-PET metabolic volume products (MVPs) of the entire brain, cerebral cortex, basal ganglia, and cerebellum were measured, before and after R-CHOP therapy. Whole-body total lesion glycolysis (TLG) was also measured. Thirty-eight patients were included, of whom 18 had an appropriate end-of-treatment FDG-PET scan. There were no significant differences (P > 0.199) between pre- and post-treatment brain glucose metabolism metrics. Low basal ganglia MVP was associated with a significantly worse progression-free survival (PFS) and overall survival (OS) (P = 0.020 and P = 0.032), and low cerebellar MVP was associated with a significantly worse OS (P = 0.034). There were non-significant very weak correlations between pretreatment brain glucose metabolism metrics and TLG. In the multivariate Cox regression, only the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) remained an independent predictor of PFS (hazard ratio 3.787, P = 0.007) and OS (hazard ratio 2.903, P = 0.0345). Brain glucose metabolism was not affected by R-CHOP therapy. Low pretreatment brain glucose metabolism was associated with a worse outcome, but did not surpass the predictive value of the NCCN-IPI. © The Foundation Acta Radiologica 2015.

  10. Prediction of Central Nervous System Relapse of Diffuse Large B-Cell Lymphoma Using Pretherapeutic [18F]2-Fluoro-2-Deoxyglucose (FDG) Positron Emission Tomography/Computed Tomography.

    Science.gov (United States)

    Song, Yoo Sung; Lee, Won Woo; Lee, Jong Seok; Kim, Sang Eun

    2015-11-01

    Central nervous system (CNS) relapse of diffuse large B-cell lymphoma (DLBCL) is a rare complication, but has a poor prognosis with unknown pathophysiology. Recent trials of CNS prophylaxis have shown to be ineffective, despite patient's selection using several known clinical risk factors. In this study, the authors evaluated the value of pretreatment [F]2-Fluoro-2-deoxyglucose positron emission tomography in predicting CNS relapse in DLBCL patients.The authors analyzed 180 pathologically confirmed DLBCL patients, retrospectively. Patients underwent [F]2-Fluoro-2-deoxyglucose positron emission tomography/computed tomography before first line rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone therapy. Clinical characteristics were evaluated and total lesion glycolysis (TLG) with a threshold margin of 50% was calculated.Among age, sex, Ann Arbor stage, International Prognostic Index, revised International Prognostic Index, high serum lactate dehydrogenase level, presence of B symptoms, bulky disease (≥10 cm), extranodal lesion involvement, bone marrow involvement, high metabolic tumor volume ( >450 mL), and high TLG50 (>2000), the high TLG50 was the only significant prognostic factor for predicting CNS relapse in a multivariate analysis (P = 0.04). Kaplan-Meir survival analysis between high TLG50 (>2000) and low TLG50 (≤2000) groups revealed significantly different mean progression free survival (PFS) of 1317.2 ± 134.3 days and 1968.6 ± 18.3 days, respectively (P positron emission tomography/computed tomography is the most significant predictor of CNS relapse in un-treated DLBCL patients.

  11. Rational Targeting of Cellular Cholesterol in Diffuse Large B-Cell Lymphoma (DLBCL) Enabled by Functional Lipoprotein Nanoparticles: A Therapeutic Strategy Dependent on Cell of Origin.

    Science.gov (United States)

    Rink, Jonathan S; Yang, Shuo; Cen, Osman; Taxter, Tim; McMahon, Kaylin M; Misener, Sol; Behdad, Amir; Longnecker, Richard; Gordon, Leo I; Thaxton, C Shad

    2017-11-06

    Cancer cells have altered metabolism and, in some cases, an increased demand for cholesterol. It is important to identify novel, rational treatments based on biology, and cellular cholesterol metabolism as a potential target for cancer is an innovative approach. Toward this end, we focused on diffuse large B-cell lymphoma (DLBCL) as a model because there is differential cholesterol biosynthesis driven by B-cell receptor (BCR) signaling in germinal center (GC) versus activated B-cell (ABC) DLBCL. To specifically target cellular cholesterol homeostasis, we employed high-density lipoprotein-like nanoparticles (HDL NP) that can generally reduce cellular cholesterol by targeting and blocking cholesterol uptake through the high-affinity HDL receptor, scavenger receptor type B-1 (SCARB1). As we previously reported, GC DLBCL are exquisitely sensitive to HDL NP as monotherapy, while ABC DLBCL are less sensitive. Herein, we report that enhanced BCR signaling and resultant de novo cholesterol synthesis in ABC DLBCL drastically reduces the ability of HDL NPs to reduce cellular cholesterol and induce cell death. Therefore, we combined HDL NP with the BCR signaling inhibitor ibrutinib and the SYK inhibitor R406. By targeting both cellular cholesterol uptake and BCR-associated de novo cholesterol synthesis, we achieved cellular cholesterol reduction and induced apoptosis in otherwise resistant ABC DLBCL cell lines. These results in lymphoma demonstrate that reduction of cellular cholesterol is a powerful mechanism to induce apoptosis. Cells rich in cholesterol require HDL NP therapy to reduce uptake and molecularly targeted agents that inhibit upstream pathways that stimulate de novo cholesterol synthesis, thus, providing a new paradigm for rationally targeting cholesterol metabolism as therapy for cancer.

  12. Putative cruciform DNA structures at BCL6 breakpoint region may explain BCL6 translocation in diffuse large B-Cell lymphoma

    International Nuclear Information System (INIS)

    Bhatelia, Khyati D.; Nambiar, Mridula; Choudhary, Bibha; Raghvan, Sathees C.

    2010-01-01

    Cancer is a disease characterized by uncontrolled proliferation of cells, caused by genetic alterations such as chromosomal translocations, which are present in almost all hematological malignancies. Diffuse Large B-cell Lymphoma (DLBL) is the most common non-Hodgkin's lymphoma, comprising 40-50% of all lymphomas both in India and worldwide, and is characterized by BCL6 chromosomal translocation. However, the mechanism of this translocation is completely unknown. By mapping of translocation breakpoints from patients, we have identified three breakpoint cluster regions at 5' UTR of BCL6 gene. Bioinformatics analysis of cluster II, which possesses majority of breakpoints, this region may form cruciform DNA structures. Gel mobility shift assays using oligomeric DNA from the region suggested that a portion of cluster II folded into hairpin structures. Mutations to the wild type sequences disrupted hairpin formation. Circular dichroism studies on BCL6 oligomers resulted in a spectra containing two overlapping peaks at 265 nm and 285 nm, confirming hairpin structure. Further, the structure was destroyed upon heating, and reformed when appropriate conditions were provided. P1 nuclease assay in conjunction with KMnO 4 probing suggested that the structure possessed an eight nucleotide double-stranded stem and a nine nucleotide loop. To further understand the mechanism of BCL6 translocation in vivo, human cells were transfected with episomes harboring cluster II region and the results obtained will be discussed. Hence, our results suggest the formation of a putative cruciform DNA structure at BCL6 breakpoint region and that may facilitate breakage at BCL6 gene explaining chromosomal translocations in DLBL. (author)

  13. Possible Role of GADD45γ Methylation in Diffuse Large B-Cell Lymphoma: Does It Affect the Progression and Tissue Involvement?

    Directory of Open Access Journals (Sweden)

    İkbal Cansu Barış

    2015-12-01

    Full Text Available INTRODUCTION: Diffuse large B-cell lymphoma (DLBCL is the most common type of non-Hodgkin lymphoma among adults and is characterized by heterogeneous clinical, immunophenotypic, and genetic features. Different mechanisms deregulating cell cycle and apoptosis play a role in the pathogenesis of DLBCL. Growth arrest DNA damage-inducible 45 (GADD45γ is an important gene family involved in these mechanisms. The aims of this study are to determine the frequency of GADD45γ methylation, to evaluate the correlation between GADD45γ methylation and protein expression, and to investigate the relation between methylation status and clinicopathologic parameters in DLBCL tissues and reactive lymphoid node tissues from patients with reactive lymphoid hyperplasia. METHODS: Thirty-six tissue samples of DLBCL and 40 nonmalignant reactive lymphoid node tissues were analyzed in this study. Methylation-sensitive high-resolution melting analysis was used for the determination of GADD45γ methylation status. The GADD45γ protein expression was determined by immunohistochemistry. RESULTS: GADD45γ methylation was frequent (50.0% in DLBCL. It was also significantly higher in advanced-stage tumors compared with early-stage (p=0.041. In contrast, unmethylated GADD45γ was associated with nodal involvement as the primary anatomical site (p=0.040. DISCUSSION AND CONCLUSION: The results of this study show that, in contrast to solid tumors, the frequency of GADD45γ methylation is higher and this epigenetic alteration of GADD45γ may be associated with progression in DLBCL. In addition, nodal involvement is more likely to be present in patients with unmethylated GADD45γ.

  14. Genomic profiling of plasmablastic lymphoma using array comparative genomic hybridization (aCGH: revealing significant overlapping genomic lesions with diffuse large B-cell lymphoma

    Directory of Open Access Journals (Sweden)

    Lu Xin-Yan

    2009-11-01

    Full Text Available Abstract Background Plasmablastic lymphoma (PL is a subtype of diffuse large B-cell lymphoma (DLBCL. Studies have suggested that tumors with PL morphology represent a group of neoplasms with clinopathologic characteristics corresponding to different entities including extramedullary plasmablastic tumors associated with plasma cell myeloma (PCM. The goal of the current study was to evaluate the genetic similarities and differences among PL, DLBCL (AIDS-related and non AIDS-related and PCM using array-based comparative genomic hybridization. Results Examination of genomic data in PL revealed that the most frequent segmental gain (> 40% include: 1p36.11-1p36.33, 1p34.1-1p36.13, 1q21.1-1q23.1, 7q11.2-7q11.23, 11q12-11q13.2 and 22q12.2-22q13.3. This correlated with segmental gains occurring in high frequency in DLBCL (AIDS-related and non AIDS-related cases. There were some segmental gains and some segmental loss that occurred in PL but not in the other types of lymphoma suggesting that these foci may contain genes responsible for the differentiation of this lymphoma. Additionally, some segmental gains and some segmental loss occurred only in PL and AIDS associated DLBCL suggesting that these foci may be associated with HIV infection. Furthermore, some segmental gains and some segmental loss occurred only in PL and PCM suggesting that these lesions may be related to plasmacytic differentiation. Conclusion To the best of our knowledge, the current study represents the first genomic exploration of PL. The genomic aberration pattern of PL appears to be more similar to that of DLBCL (AIDS-related or non AIDS-related than to PCM. Our findings suggest that PL may remain best classified as a subtype of DLBCL at least at the genome level.

  15. Serum lactate dehydrogenase with a systemic inflammation score is useful for predicting response and survival in patients with newly diagnosed diffuse large B-cell lymphoma.

    Science.gov (United States)

    Jung, Sung-Hoon; Yang, Deok-Hwan; Ahn, Jae-Sook; Kim, Yeo-Kyeoung; Kim, Hyeoung-Joon; Lee, Je-Jung

    2015-01-01

    We evaluated the relationship between serum lactate dehydrogenase (LDH) level with systemic inflammation score and survival in 213 patients with diffuse large B-cell lymphoma (DLBCL) receiving R-CHOP chemotherapy. The patients were classified into 3 groups based on LDH with the Glasgow Prognostic Score (L-GPS). A score of 2 was assigned to patients with elevated C-reactive protein, hypoalbuminemia and elevated LDH, a score of 1 to those with one or two abnormalities and a score of 0 to those with no abnormality. In multivariate analysis, independent poor prognostic factors for progression-free survival were L-GPS 2 [hazard ratio (HR) 5.415, p = 0.001], Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2 (HR 3.504, p = 0.001) and bulky lesion (HR 2.030, p = 0.039). Independent poor prognostic factors for overall survival were L-GPS 2 (HR 5.898, p = 0.001) and ECOG PS ≥2 (HR 3.525, p = 0.001). The overall response rate for the R-CHOP chemotherapy decreased according to the L-GPS; it was 96.7% at L-GPS 0, 87% at L-GPS 1 and 75% at L-GPS 2 (p = 0.009). L-GPS based on systemic inflammatory indicators may be a useful clinical prognostic indicator for survival, and predicts the response for R-CHOP chemotherapy in patients with newly diagnosed DLBCL. © 2014 S. Karger AG, Basel.

  16. Prognostic impact of sarcopenia in patients with diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone.

    Science.gov (United States)

    Go, Se-Il; Park, Mi Jung; Song, Haa-Na; Kim, Hoon-Gu; Kang, Myoung Hee; Lee, Hyang Rae; Kim, Yire; Kim, Rock Bum; Lee, Soon Il; Lee, Gyeong-Won

    2016-12-01

    Sarcopenia is known to be related to an increased risk of chemotherapy toxicity and to a poor prognosis in patients with malignancy. We assessed the prognostic role of sarcopenia in patients with diffuse large B-cell lymphoma (DLBCL). In total, 187 consecutive patients with DLBCL treated with induction rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) immunochemotherapy were reviewed. Sarcopenia was defined as the lowest sex-specific quartile of the skeletal muscle index, calculated by dividing the pectoralis muscle area by the height. Clinical outcomes were compared between the sarcopenic and non-sarcopenic groups. A nomogram was constructed from the Cox regression model for overall survival (OS). Treatment-related mortality (21.7 vs. 5.0%, P  = 0.002) and early discontinuation of treatment (32.6 vs. 14.9%, P  = 0.008) were more common in the sarcopenic group than in the non-sarcopenic group. The 5 year progression-free survival (PFS) rates were 35.3% in the sarcopenic group and 65.8% in the non-sarcopenic group ( P  Sarcopenia and the five variables of the International Prognostic Index (IPI) were independent prognostic factors in a multivariate analysis for PFS and OS and were used to construct the nomogram. The calibration plot showed good agreement between the nomogram predictions and actual observations. The c index of the nomogram (0.80) was higher than those of other prognostic indices (IPI, 0.77, P  = 0.009; revised-IPI, 0.74, P  Sarcopenia is associated with intolerance to standard R-CHOP chemotherapy as well as a poor prognosis. Moreover, sarcopenia itself can be included in prognostic models in DLBCL.

  17. A comparison of pectoralis versus lumbar skeletal muscle indices for defining sarcopenia in diffuse large B-cell lymphoma - two are better than one.

    Science.gov (United States)

    Go, Se-Il; Park, Mi Jung; Song, Haa-Na; Kim, Hoon-Gu; Kang, Myoung Hee; Kang, Jung Hun; Kim, Hye Ree; Lee, Gyeong-Won

    2017-07-18

    Sarcopenia is known to be associated with poor clinical outcome in patients with diffuse large B-cell lymphoma (DLBCL). There is no consensus concerning the optimal method to define sarcopenia in DLBCL. We retrospectively reviewed 193 DLBCL patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. Sarcopenia was classified by the region where the pretreatment skeletal muscle index (SMI) was measured. Both the sarcopenia-L3 and sarcopenia-pectoralis muscle (PM) groups had increased incidences of severe treatment-related toxicities and treatment discontinuation compared with the non-sarcopenia-L3 and non-sarcopenia-PM groups, respectively. The sarcopenia-L3 and non-sarcopenia-L3 groups had 5-year overall survival (OS) rates of 40.5% and 67.8% (p sarcopenia-PM and non-sarcopenia-PM groups had 5-year OS rates of 35.9% and 69.0% (p sarcopenia-L3 alone and sarcopenia-PM alone groups were compared, there were no differences in baseline characteristics, treatment toxicity, or survival. In multivariate analysis, when compared with the non-sarcopenia-both group, OS was significantly worse in the sarcopenia-both group (HR, 2.480; 95% CI, 1.284 - 4.792; p = 0.007), but not in patients with either sarcopenia-L3 alone or sarcopenia-PM alone (p = 0.151). L3- and PM-SMIs are equally useful to define sarcopenia, which is related to intolerance to R-CHOP therapy and to worse survival in patients with DLBCL. More prognostic information can be obtained when these two SMIs are combined to define sarcopenia.

  18. Disruption of Aneuploidy and Senescence Induced by Aurora Inhibition Promotes Intrinsic Apoptosis in Double Hit or Double Expressor Diffuse Large B-cell Lymphomas.

    Science.gov (United States)

    Islam, Shariful; Qi, Wenqing; Morales, Carla; Cooke, Laurence; Spier, Catherine; Weterings, Eric; Mahadevan, Daruka

    2017-10-01

    Double hit (DH) or double expressor (DE) diffuse large B-cell lymphomas (DLBCL) are aggressive non-Hodgkin's lymphomas (NHL) with translocations and/or overexpressions of MYC and BCL-2 , which are difficult to treat. Aurora kinase (AK) inhibition with alisertib in DH/DE-DLBCL induces cell death in ∼30%, while ∼70% are aneuploid and senescent cells (AASC), a mitotic escape mechanism contributing to drug resistance. These AASCs elaborated a high metabolic rate by increased AKT/mTOR and ERK/MAPK activity via BTK signaling through the chronic active B-cell receptor (BCR) pathway. Combinations of alisertib + ibrutinib or alisertib + ibrutinib + rituximab significantly reduced AASCs with enhanced intrinsic cell death. Inhibition of AK + BTK reduced phosphorylation of AKT/mTOR and ERK-1/2, upregulated phospho-H2A-X and Chk-2 (DNA damage), reduced Bcl-6, and decreased Bcl-2 and Bcl-xL and induced apoptosis by PARP cleavage. In a DE-DLBCL SCID mouse xenograft model, ibrutinib alone was inactive, while alisertib + ibrutinib was additive with a tumor growth inhibition (TGI) rate of ∼25%. However, TGI for ibrutinib + rituximab was ∼50% to 60%. In contrast, triple therapy showed a TGI rate of >90%. Kaplan-Meier survival analysis showed that 67% of mice were alive at day 89 with triple therapy versus 20% with ibrutinib + rituximab. All treatments were well tolerated with no changes in body weights. A novel triple therapy consisting of alisertib + ibrutinib + rituximab inhibits AASCs induced by AK inhibition in DH/DE-DLBCL leading to a significant antiproliferative signal, enhanced intrinsic apoptosis and may be of therapeutic potential in these lymphomas. Mol Cancer Ther; 16(10); 2083-93. ©2017 AACR . ©2017 American Association for Cancer Research.

  19. Detection of the value of consecutive serum total light chain (sTLC) in patients diagnosed with diffuse large B cell lymphoma.

    Science.gov (United States)

    Zhai, Linzhu; Zhao, Yuanyuan; Peng, Songguo; Zhu, Ke; Yu, Rongjian; Chen, Hailong; Lin, Tongyu; Lin, Lizhu

    2016-12-01

    There are limited data on serum total light chain (sTLC) in lymphoma and its relative role on the outcome of diffuse large B cell lymphoma (DLBCL) patients. Blood samples from 46 cases newly diagnosed with DLBCL were collected consecutively during chemotherapy to detect sTLC, IgG, IgA, and IgM levels. Clinical data and survival outcomes were analyzed according to the results of sTLC measurements. In summary, 22 patients (47.8 %) had abnormal k or λ light chain, respectively, and 6 patients (13.0 %) had both abnormal k and λ light chains before chemotherapy. Patients with elevated k light chain more frequently displayed multiple extra-nodal organ involvement (P = 0.01) and had an inferior overall survival (OS) (P = 0.041) and progression-free survival (PFS) (P = 0.044) compared to patients with normal level of k light chain. Furthermore, patients with elevated level of both k and λ also exhibited significant association with shorter OS (P = 0.002) and PFS (P = 0.009). Both elevated k alone and concurrent elevated k and λ had independent adverse effects on PFS (P = 0.031 and P = 0.019, respectively). sTLC level was reduced gradually by treatment in this study and reached the lowest point after the fourth cycle of chemotherapy, which was consistent with the disease behavior during chemotherapy. Considering the small sample size of this study, these results should be confirmed in a larger prospective study.

  20. Additional Survival Benefit of Involved-Lesion Radiation Therapy After R-CHOP Chemotherapy in Limited Stage Diffuse Large B-Cell Lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Jeanny [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Il Han, E-mail: ihkim@snu.ac.kr [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Cancer Research Institute, Seoul National University College of Medicine, Seoul (Korea, Republic of); Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul (Korea, Republic of); Kim, Byoung Hyuck [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Tae Min; Heo, Dae Seog [Department of Internal Medicine, Seoul National University Hospital, Seoul (Korea, Republic of)

    2015-05-01

    Purpose: The purpose of this study was to evaluate the role of involved-lesion radiation therapy (ILRT) after rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy in limited stage diffuse large B-cell lymphoma (DLBCL) by comparing outcomes of R-CHOP therapy alone with R-CHOP followed by ILRT. Methods and Materials: We identified 198 patients treated with R-CHOP (median, 6 cycles) for pathologically confirmed DLBCL of limited stage from July 2004 to December 2012. Clinical characteristics of these patients were 33% with stage I and 66.7% with stage II; 79.8% were in the low or low-intermediate risk group; 13.6% had B symptoms; 29.8% had bulky tumors (≥7 cm); and 75.3% underwent ≥6 cycles of R-CHOP therapy. RT was given to 43 patients (21.7%) using ILRT technique, which included the prechemotherapy tumor volume with a median margin of 2 cm (median RT dose: 36 Gy). Results: After a median follow-up of 40 months, 3-year progression-free survival (PFS) and overall survival (OS) were 85.8% and 88.9%, respectively. Multivariate analysis showed ≥6 cycles of R-CHOP (PFS, P=.004; OS, P=.004) and ILRT (PFS, P=.021; OS, P=.014) were favorable prognosticators of PFS and OS. A bulky tumor (P=.027) and response to R-CHOP (P=.012) were also found to be independent factors of OS. In subgroup analysis, the effect of ILRT was prominent in patients with a bulky tumor (PFS, P=.014; OS, P=.030) or an elevated level of serum lactate dehydrogenase (LDH; PFS, P=.004; OS, P=.012). Conclusions: Our results suggest that ILRT after R-CHOP therapy improves PFS and OS in patients with limited stage DLBCL, especially in those with bulky disease or an elevated serum LDH level.

  1. Predictors of Local Recurrence After Rituximab-Based Chemotherapy Alone in Stage III and IV Diffuse Large B-Cell Lymphoma: Guiding Decisions for Consolidative Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Jegadeesh, Naresh; Rajpara, Raj; Esiashvili, Natia; Shi, Zheng [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Liu, Yuan [Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Department of Biostatistics and Bioinformatics Shared Resource, Emory University, Atlanta, Georgia (United States); Okwan-Duodu, Derrick [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Flowers, Christopher R. [Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Department of Medical Oncology, Emory University, Atlanta, Georgia (United States); Khan, Mohammad K., E-mail: drkhurram2000@gmail.com [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute, Emory University, Atlanta, Georgia (United States)

    2015-05-01

    Purpose: The role of consolidative radiation therapy (RT) for stage III and IV diffuse large B-cell lymphoma (DLBCL) in the era of rituximab is not well defined. There is evidence that some patients with bulky disease may benefit, but patient selection criteria are not well established. We sought to identify a subset of patients who experienced a high local failure rate after receiving rituximab-based chemotherapy alone and hence may benefit from the addition of consolidative RT. Methods and Materials: Two hundred eleven patients with stage III and IV DLBCL treated between August 1999 and January 2012 were reviewed. Of these, 89 had a complete response to systemic therapy including rituximab and received no initial RT. Kaplan-Meier analysis and Cox proportional hazards regression were performed, with local recurrence (LR) as the primary outcome. Results: The median follow-up time was 43.9 months. Fifty percent of patients experienced LR at 5 years. In multivariate analysis, tumor ≥5 cm and stage III disease were associated with increased risk of LR. The 5-year LR-free survival was 47.4% for patients with ≥5-cm lesions versus 74.7% for patients with <5-cm lesions (P=.01). In patients with <5-cm tumors, the maximum standardized uptake value (SUVmax) was ≥15 in all patients with LR. The 5-year LR-free survival was 100% in SUV<15 versus 68.8% in SUV≥15 (P=.10). Conclusions: Advanced-stage DLBCL patients with stage III disease or with disease ≥5 cm appear to be at an increased risk for LR. Patients with <5-cm disease and SUVmax ≥15 may be at higher risk for LR. These patients may benefit from consolidative RT after chemoimmunotherapy.

  2. Additional survival benefit of involved-lesion radiation therapy after R-CHOP chemotherapy in limited stage diffuse large B-cell lymphoma.

    Science.gov (United States)

    Kwon, Jeanny; Kim, Il Han; Kim, Byoung Hyuck; Kim, Tae Min; Heo, Dae Seog

    2015-05-01

    The purpose of this study was to evaluate the role of involved-lesion radiation therapy (ILRT) after rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy in limited stage diffuse large B-cell lymphoma (DLBCL) by comparing outcomes of R-CHOP therapy alone with R-CHOP followed by ILRT. We identified 198 patients treated with R-CHOP (median, 6 cycles) for pathologically confirmed DLBCL of limited stage from July 2004 to December 2012. Clinical characteristics of these patients were 33% with stage I and 66.7% with stage II; 79.8% were in the low or low-intermediate risk group; 13.6% had B symptoms; 29.8% had bulky tumors (≥ 7 cm); and 75.3% underwent ≥ 6 cycles of R-CHOP therapy. RT was given to 43 patients (21.7%) using ILRT technique, which included the prechemotherapy tumor volume with a median margin of 2 cm (median RT dose: 36 Gy). After a median follow-up of 40 months, 3-year progression-free survival (PFS) and overall survival (OS) were 85.8% and 88.9%, respectively. Multivariate analysis showed ≥ 6 cycles of R-CHOP (PFS, P=.004; OS, P=.004) and ILRT (PFS, P=.021; OS, P=.014) were favorable prognosticators of PFS and OS. A bulky tumor (P=.027) and response to R-CHOP (P=.012) were also found to be independent factors of OS. In subgroup analysis, the effect of ILRT was prominent in patients with a bulky tumor (PFS, P=.014; OS, P=.030) or an elevated level of serum lactate dehydrogenase (LDH; PFS, P=.004; OS, P=.012). Our results suggest that ILRT after R-CHOP therapy improves PFS and OS in patients with limited stage DLBCL, especially in those with bulky disease or an elevated serum LDH level. Copyright © 2015. Published by Elsevier Inc.

  3. Predictors of Local Recurrence After Rituximab-Based Chemotherapy Alone in Stage III and IV Diffuse Large B-Cell Lymphoma: Guiding Decisions for Consolidative Radiation

    International Nuclear Information System (INIS)

    Jegadeesh, Naresh; Rajpara, Raj; Esiashvili, Natia; Shi, Zheng; Liu, Yuan; Okwan-Duodu, Derrick; Flowers, Christopher R.; Khan, Mohammad K.

    2015-01-01

    Purpose: The role of consolidative radiation therapy (RT) for stage III and IV diffuse large B-cell lymphoma (DLBCL) in the era of rituximab is not well defined. There is evidence that some patients with bulky disease may benefit, but patient selection criteria are not well established. We sought to identify a subset of patients who experienced a high local failure rate after receiving rituximab-based chemotherapy alone and hence may benefit from the addition of consolidative RT. Methods and Materials: Two hundred eleven patients with stage III and IV DLBCL treated between August 1999 and January 2012 were reviewed. Of these, 89 had a complete response to systemic therapy including rituximab and received no initial RT. Kaplan-Meier analysis and Cox proportional hazards regression were performed, with local recurrence (LR) as the primary outcome. Results: The median follow-up time was 43.9 months. Fifty percent of patients experienced LR at 5 years. In multivariate analysis, tumor ≥5 cm and stage III disease were associated with increased risk of LR. The 5-year LR-free survival was 47.4% for patients with ≥5-cm lesions versus 74.7% for patients with <5-cm lesions (P=.01). In patients with <5-cm tumors, the maximum standardized uptake value (SUVmax) was ≥15 in all patients with LR. The 5-year LR-free survival was 100% in SUV<15 versus 68.8% in SUV≥15 (P=.10). Conclusions: Advanced-stage DLBCL patients with stage III disease or with disease ≥5 cm appear to be at an increased risk for LR. Patients with <5-cm disease and SUVmax ≥15 may be at higher risk for LR. These patients may benefit from consolidative RT after chemoimmunotherapy

  4. Patients with primary breast and primary female genital tract diffuse large B cell lymphoma have a high frequency of MYD88 and CD79B mutations.

    Science.gov (United States)

    Cao, Xin-Xin; Li, Jian; Cai, Hao; Zhang, Wei; Duan, Ming-Hui; Zhou, Dao-Bin

    2017-11-01

    This study is to retrospectively evaluate the prevalence of MYD88 and CD79B mutations and the clinicopathologic characteristics of patients with primary diffuse large B cell lymphoma (DLBCL) of the female genital tract and breast. The characteristics, treatments, and outcomes of 19 patients diagnosed with primary DLBCL of the female genital tract and breast, who had formalin-fixed and paraffin-embedded tissues obtained from diagnostic samples diagnosed between January 2004 and June 2016, were analyzed retrospectively. Nineteen female patients (7 with primary breast and 12 with primary female genital tract DLBCL) were included in this retrospective study. Eleven patients (57.9%) carried a MYD88 mutation, including 10 with MYD8 L265P and 1 with the MYD88 L265S mutation. Seven patients (36.8%) harbored a CD79B mutation, which included two cases with CD79B Y196H, two cases with CD79B Y196N, one case with CD79B Y196D, one case with CD79B Y196F, and one case with CD79B Y196X. Four cases had both MYD88 and CD79B mutations. The clinicopathologic parameters, progression-free survival (PFS), and overall survival (OS) of the MYD88 mutation-carrying group were not significantly different from those of the MYD88 wild-type group except for higher LDH levels. Six patients received cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP), while 13 patients received rituximab plus CHOP, and 13 patients received central nervous system prophylaxis. The median OS and PFS were 73 and 56 months, respectively. Patients with primary breast and primary female genital tract DLBCL have a high frequency of MYD88 and CD79B mutations. The presence of these mutations does not affect survival but may offer additional therapeutic options.

  5. Alteration of the gene expression profile of T-cell receptor αβ-modified T-cells with diffuse large B-cell lymphoma specificity.

    Science.gov (United States)

    Zha, Xianfeng; Yin, Qingsong; Tan, Huo; Wang, Chunyan; Chen, Shaohua; Yang, Lijian; Li, Bo; Wu, Xiuli; Li, Yangqiu

    2013-05-01

    Antigen-specific, T-cell receptor (TCR)-modified cytotoxic T lymphocytes (CTLs) that target tumors are an attractive strategy for specific adoptive immunotherapy. Little is known about whether there are any alterations in the gene expression profile after TCR gene transduction in T cells. We constructed TCR gene-redirected CTLs with specificity for diffuse large B-cell lymphoma (DLBCL)-associated antigens to elucidate the gene expression profiles of TCR gene-redirected T-cells, and we further analyzed the gene expression profile pattern of these redirected T-cells by Affymetrix microarrays. The resulting data were analyzed using Bioconductor software, a two-fold cut-off expression change was applied together with anti-correlation of the profile ratios to render the microarray analysis set. The fold change of all genes was calculated by comparing the three TCR gene-modified T-cells and a negative control counterpart. The gene pathways were analyzed using Bioconductor and Kyoto Encyclopedia of Genes and Genomes. Identical genes whose fold change was greater than or equal to 2.0 in all three TCR gene-redirected T-cell groups in comparison with the negative control were identified as the differentially expressed genes. The differentially expressed genes were comprised of 33 up-regulated genes and 1 down-regulated gene including JUNB, FOS, TNF, INF-γ, DUSP2, IL-1B, CXCL1, CXCL2, CXCL9, CCL2, CCL4, and CCL8. These genes are mainly involved in the TCR signaling, mitogen-activated protein kinase signaling, and cytokine-cytokine receptor interaction pathways. In conclusion, we characterized the gene expression profile of DLBCL-specific TCR gene-redirected T-cells. The changes corresponded to an up-regulation in the differentiation and proliferation of the T-cells. These data may help to explain some of the characteristics of the redirected T-cells.

  6. Feasibility of abbreviated cycles of immunochemotherapy for completely resected limited-stage CD20+ diffuse large B-cell lymphoma (CISL 12-09).

    Science.gov (United States)

    Yoon, Dok Hyun; Sohn, Byeong Seok; Oh, Sung Yong; Lee, Won-Sik; Lee, Sang Min; Yang, Deok-Hwan; Huh, Jooryung; Suh, Cheolwon

    2017-02-21

    The appropriate number of chemotherapy cycles for limited stage diffuse large B-cell lymphoma (DLBCL) patients without gross residual lesions after complete resection, has not been specifically questioned. We performed a multicenter, single-arm, phase 2 study to investigate the feasibility of 3 cycles of abbreviated R-CHOP chemotherapy in low-risk patients with completely resected localized CD20+ DLBCL. Between December 2010 and May 2013, we recruited 23 patients. One was excluded due to ineligibility, and hence, 22 were included in the final analysis. The primary sites comprised the intestine (n = 15), cervical lymph nodes (n = 4), stomach (n = 1), tonsil (n = 1), and spleen (n = 1). All patients successfully completed the 3 cycles of planned R-CHOP chemotherapy. Over a median follow-up of 39.5 months (95% confidence interval, 29.9-47.1 months), both the estimated 2-year disease-free survival and overall survival rates was 95% confidence interval, 85.9-104.1%. Only one patient with an international prognostic index of 2 experienced relapse and died. The most common grade 3 or 4 toxicity condition included neutropenia (n = 8, 36.4%). Three patients experienced grade 3 febrile neutropenia, but no grade 3 or 4 non-hematologic toxicity was observed. DLBCL patients without residual lesions after resection were enrolled and R-CHOP chemotherapy was repeated at 3-week-intervals over 3 cycles. The primary endpoint was 2-year disease-free survival. Three cycles of abbreviated R-CHOP immunochemotherapy is feasible for completely resected low risk localized DLBCL.

  7. CD4+ T cell-mediated cytotoxicity is associated with MHC class II expression on malignant CD19+ B cells in diffuse large B cell lymphoma.

    Science.gov (United States)

    Zhou, Yong; Zha, Jie; Lin, Zhijuan; Fang, Zhihong; Zeng, Hanyan; Zhao, Jintao; Luo, Yiming; Li, Zhifeng; Xu, Bing

    2018-01-15

    Diffuse large B cell lymphoma (DLBCL) is a common B cell malignancy with approximately 30% of patients present relapsed or refractory disease after first-line therapy. Research of further treatment options is needed. Cytotoxic CD4 + T cells express cytolytic molecules and have potential antitumor function. Here, we showed that the CD19 + cells from DLBCL patients presented significantly reduced expression of MHC II molecules than those from healthy controls. Three years after the first-line treatment, patients that presented relapsed disease had significantly lower MHC II expression on their CD19 + cells than patients who did not show recurrence. Examining cytotoxic CD4 + T cells show that DLBCL patients presented significantly elevated frequencies of granzyme A-, granzyme B-, and/or perforin-expressing cytotoxic CD4 + T cells. Also, frequency of cytotoxic CD4 + T cells in DLBCL patients was positively correlated with the MHC II expression level. Subsequently, the cytotoxic potential of CD4 + T cells against autologous CD19 + cells was investigated. We found that the cytotoxic potential of CD4 + T cells was highest in MHC II-high, intermediate in MHC II-mid, and lowest in MHC II-low patients. The percentage of MHC II-expressing viable CD19 + cells presented a significant reduction after longer incubation with cytotoxic CD4 + T cells, suggesting that cytotoxic CD4 + T cells preferentially eliminated MHC II-expressing CD19 + cells. Blocking MHC II on CD19 + cells significantly reduced the cytolytic capacity of CD4 + T cells. Despite these discoveries, the frequency of cytotoxic CD4 + T cells did not predict the clinical outcome of DLBCL patients. Together, these results demonstrated that cytotoxic CD4 + T cells presented an MHC II-dependent cytotoxic potential against autologous CD19 + cells and could potentially represent a future treatment option for DLBCL. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Circulating CXCR5+CD4+ T cells assist in the survival and growth of primary diffuse large B cell lymphoma cells through interleukin 10 pathway

    International Nuclear Information System (INIS)

    Cha, Zhanshan; Qian, Guangfang; Zang, Yan; Gu, Haihui; Huang, Yanyan; Zhu, Lishuang; Li, Jinqi; Liu, Yang; Tu, Xiaohua; Song, Haihan; Qian, Baohua

    2017-01-01

    Diffuse large B cell lymphoma (DLBCL) is a common and aggressive cancer caused by the malignant transformation of B cells. Although it has been established that the follicular helper T (Tfh) cells play a central role in B cell development, little information is available on their involvement in DLBCL pathogenesis. We studied the role of the peripheral Tfh equivalent, the CXCR5"+ CD4"+ T cells, in DLBCL. Data showed that compared to CXCR5"- CD4"+ T cells, CXCR5"+ CD4"+ T cells were significantly more effective at promoting the proliferation as well as inhibiting the apoptosis of primary autologous DLBCL tumor cells. Surprisingly, we found that at equal cell numbers, CXCR5"+ CD4"+ T cells in DLBCL patients secreted significantly less interleukin (IL)-21 than CXCR5"- CD4"+ T cells, while the level of IL-10 secretion was significant elevated in the CXCR5"+ compartment compared to the CXCR5"- compartment. Neutralization of IL-10 in the primary DLBCL-CXCR5"+ CD4"+ T cell coculture compromised the CXCR5"+ CD4"+ T cell-mediated pro-tumor effects, in a manner that was dependent on the concentration of anti-IL-10 antibodies. The CXCR5"+ compartment also contained significantly lower frequencies of cytotoxic CD4"+ T cells than the CXCR5"- compartment. In conclusion, our investigations discovered a previously unknown pro-tumor role of CXCR5-expressing circulating CD4"+ T cells, which assisted the survival and proliferation of primary DLBCL cells through IL-10. - Highlights: • We studied the role of the peripheral Tfh in DLBCL. • Tfh were effective at promoting the proliferation of primary DLBCL tumor cells. • Tfh were effective at inhibiting the apoptosis of primary DLBCL tumor cells. • IL-10 secretion in Tfh was significant elevated in DLBCL. • Neutralization of IL-10 compromised Tfh-mediated pro-tumor effects.

  9. Ectopic Expression of Homeobox Gene NKX2-1 in Diffuse Large B-Cell Lymphoma Is Mediated by Aberrant Chromatin Modifications

    Science.gov (United States)

    Nagel, Stefan; Ehrentraut, Stefan; Tomasch, Jürgen; Quentmeier, Hilmar; Meyer, Corinna; Kaufmann, Maren; Drexler, Hans G.; MacLeod, Roderick A. F.

    2013-01-01

    Homeobox genes encode transcription factors ubiquitously involved in basic developmental processes, deregulation of which promotes cell transformation in multiple cancers including hematopoietic malignancies. In particular, NKL-family homeobox genes TLX1, TLX3 and NKX2-5 are ectopically activated by chromosomal rearrangements in T-cell neoplasias. Here, using transcriptional microarray profiling and RQ-PCR we identified ectopic expression of NKL-family member NKX2-1, in a diffuse large B-cell lymphoma (DLBCL) cell line SU-DHL-5. Moreover, in silico analysis demonstrated NKX2-1 overexpression in 5% of examined DLBCL patient samples. NKX2-1 is physiologically expressed in lung and thyroid tissues where it regulates differentiation. Chromosomal and genomic analyses excluded rearrangements at the NKX2-1 locus in SU-DHL-5, implying alternative activation. Comparative expression profiling implicated several candidate genes in NKX2-1 regulation, variously encoding transcription factors, chromatin modifiers and signaling components. Accordingly, siRNA-mediated knockdown and overexpression studies confirmed involvement of transcription factor HEY1, histone methyltransferase MLL and ubiquitinated histone H2B in NKX2-1 deregulation. Chromosomal aberrations targeting MLL at 11q23 and the histone gene cluster HIST1 at 6p22 which we observed in SU-DHL-5 may, therefore, represent fundamental mutations mediating an aberrant chromatin structure at NKX2-1. Taken together, we identified ectopic expression of NKX2-1 in DLBCL cells, representing the central player in an oncogenic regulative network compromising B-cell differentiation. Thus, our data extend the paradigm of NKL homeobox gene deregulation in lymphoid malignancies. PMID:23637834

  10. Patterns and Timing of Failure for Diffuse Large B-Cell Lymphoma After Initial Therapy in a Cohort Who Underwent Autologous Bone Marrow Transplantation for Relapse

    Energy Technology Data Exchange (ETDEWEB)

    Dhakal, Sughosh; Bates, James E. [Department of Radiation Oncology, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York (United States); Casulo, Carla; Friedberg, Jonathan W.; Becker, Michael W.; Liesveld, Jane L. [Department of Medicine, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York (United States); Constine, Louis S., E-mail: louis_constine@urmc.rochester.edu [Department of Radiation Oncology, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York (United States)

    2016-10-01

    Purpose: To evaluate the location and timing of initial recurrence in patients with diffuse large B-cell lymphoma (DLBCL) who subsequently underwent high-dose chemotherapy with autologous stem cell transplant (HDC/ASCT), to direct approaches for disease surveillance, elucidate the patterns of failure of contemporary treatment strategies, and guide adjuvant treatment decisions. Methods and Materials: We analyzed consecutive patients with DLBCL who underwent HDC/ASCT between May 1992 and March 2014 at our institution. Of the 187 evaluable patients, 8 had incomplete data, and 79 underwent HDC/ASCT as a component of initial treatment for de novo or refractory DLBCL and were excluded from further analysis. Results: The median age was 50.8 years; the median time to relapse was 1.3 years. Patients were segregated according to the initial stage at diagnosis, with early stage (ES) defined as stage I/II and advanced stage (AS) defined as stage III/IV. In total, 40.4% of the ES and 75.5% of the AS patients relapsed in sites of initial disease; 68.4% of those with ES disease and 75.0% of those with AS disease relapsed in sites of initial disease only. Extranodal relapses were common (44.7% in ES and 35.9% in AS) and occurred in a variety of organs, although gastrointestinal tract/liver (n=12) was most frequent. Conclusions: Most patients with DLBCL who relapse and subsequently undergo HDC/ASCT initially recur in the previously involved disease site(s). Time to recurrence is brief, suggesting that frequency of screening is most justifiably greatest in the early posttherapy years. © 2016 Elsevier Inc.

  11. Treatment cost and life expectancy of diffuse large B-cell lymphoma (DLBCL): a discrete event simulation model on a UK population-based observational cohort.

    Science.gov (United States)

    Wang, Han-I; Smith, Alexandra; Aas, Eline; Roman, Eve; Crouch, Simon; Burton, Cathy; Patmore, Russell

    2017-03-01

    Diffuse large B-cell lymphoma (DLBCL) is the commonest non-Hodgkin lymphoma. Previous studies examining the cost of treating DLBCL have generally focused on a specific first-line therapy alone; meaning that their findings can neither be extrapolated to the general patient population nor to other points along the treatment pathway. Based on empirical data from a representative population-based patient cohort, the objective of this study was to develop a simulation model that could predict costs and life expectancy of treating DLBCL. All patients newly diagnosed with DLBCL in the UK's population-based Haematological Malignancy Research Network ( www.hmrn.org ) in 2007 were followed until 2013 (n = 271). Mapped treatment pathways, alongside cost information derived from the National Tariff 2013/14, were incorporated into a patient-level simulation model in order to reflect the heterogeneities of patient characteristics and treatment options. The NHS and social services perspective was adopted, and all outcomes were discounted at 3.5 % per annum. Overall, the expected total medical costs were £22,122 for those treated with curative intent, and £2930 for those managed palliatively. For curative chemotherapy, the predicted medical costs were £14,966, £23,449 and £7376 for first-, second- and third-line treatments, respectively. The estimated annual cost for treating DLBCL across the UK was around £88-92 million. This is the first cost modelling study using empirical data to provide 'real world' evidence throughout the DLBCL treatment pathway. Future application of the model could include evaluation of new technologies/treatments to support healthcare decision makers, especially in the era of personalised medicine.

  12. Prognostic significance of MYC, BCL2, and BCL6 rearrangements in patients with diffuse large B-cell lymphoma treated with cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab.

    Science.gov (United States)

    Akyurek, Nalan; Uner, Aysegul; Benekli, Mustafa; Barista, Ibrahim

    2012-09-01

    Diffuse large B-cell lymphomas (DLBCLs) are a biologically heterogeneous group in which various gene alterations have been reported. The aim of this study was to investigate the frequency and prognostic impact of BCL2, BCL6, and MYC rearrangements in cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab (R-CHOP)-treated DLBCL cases. Tissue microarrays were constructed from 239 cases of DLBCL, and the expressions of CD10, BCL6, MUM1/IRF4, and BCL2 were evaluated by immunohistochemistry. MYC, BCL2, and BCL6 rearrangements were investigated by interphase fluorescence in situ hybridization on tissue microarrays. Survival analysis was constructed from 145 R-CHOP-treated patients. MYC, BCL2, and BCL6 rearrangements were detected in 14 (6%), 36 (15%), and 69 (29%) of 239 DLBCL patients. Double or triple rearrangements were detected in 7 (3%) of 239 DLBCL cases. Of these, 4 had BCL2 and MYC, 2 had BCL6 and MYC, and 1 had BCL2, BCL6, and MYC rearrangements. The prognosis of these cases was extremely poor, with a median survival of 9 months. MYC rearrangement was associated with significantly worse overall survival (P = .01), especially for the cases with GC phenotype (P = .009). BCL6 rearrangement also predicted significantly shorter overall survival (P = .04), especially for the non-GC phenotype (P = .03). BCL2 rearrangement had no prognostic impact on outcome. International Prognostic Index (P = .004) and MYC rearrangement (P = .009) were independent poor prognostic factors. Analysis of MYC gene rearrangement along with BCL2 and BCL6 is critical in identifying high-risk patients with poor prognosis. Copyright © 2011 American Cancer Society.

  13. The sensitivity of diffuse large B-cell lymphoma cell lines to histone deacetylase inhibitor-induced apoptosis is modulated by BCL-2 family protein activity.

    Directory of Open Access Journals (Sweden)

    Ryan C Thompson

    Full Text Available BACKGROUND: Diffuse large B-cell lymphoma (DLBCL is a genetically heterogeneous disease and this variation can often be used to explain the response of individual patients to chemotherapy. One cancer therapeutic approach currently in clinical trials uses histone deacetylase inhibitors (HDACi's as monotherapy or in combination with other agents. METHODOLOGY/PRINCIPAL FINDINGS: We have used a variety of cell-based and molecular/biochemical assays to show that two pan-HDAC inhibitors, trichostatin A and vorinostat, induce apoptosis in seven of eight human DLBCL cell lines. Consistent with previous reports implicating the BCL-2 family in regulating HDACi-induced apoptosis, ectopic over-expression of anti-apoptotic proteins BCL-2 and BCL-XL or pro-apoptotic protein BIM in these cell lines conferred further resistance or sensitivity, respectively, to HDACi treatment. Additionally, BCL-2 family antgonist ABT-737 increased the sensitivity of several DLBCL cell lines to vorinostat-induced apoptosis, including one cell line (SUDHL6 that is resistant to vorinostat alone. Moreover, two variants of the HDACi-sensitive SUDHL4 cell line that have decreased sensitivity to vorinostat showed up-regulation of BCL-2 family anti-apoptotic proteins such as BCL-XL and MCL-1, as well as decreased sensitivity to ABT-737. These results suggest that the regulation and overall balance of anti- to pro-apoptotic BCL-2 family protein expression is important in defining the sensitivity of DLBCL to HDACi-induced apoptosis. However, the sensitivity of DLBCL cell lines to HDACi treatment does not correlate with expression of any individual BCL-2 family member. CONCLUSIONS/SIGNIFICANCE: These studies indicate that the sensitivity of DLBCL to treatment with HDACi's is dependent on the complex regulation of BCL-2 family members and that BCL-2 antagonists may enhance the response of a subset of DLBCL patients to HDACi treatment.

  14. Rituximab plus chemotherapy as first-line treatment in Chinese patients with diffuse large B-cell lymphoma in routine practice: a prospective, multicentre, non-interventional study

    International Nuclear Information System (INIS)

    Wu, Jianqiu; Song, Yongping; Su, Liping; Xu, Li; Chen, Tingchao

    2016-01-01

    The efficacy and safety of rituximab-based chemotherapy (R-chemo), the standard regimen for patients with diffuse large B-cell lymphoma (DLBCL), which is more common in Asia than in Western countries, are well confirmed in randomized controlled trials (RCTs). However, the safety and effectiveness of R-chemo in patients who are largely excluded from RCTs have not been well characterized. This real-world study investigated the safety and effectiveness of R-chemo as first-line treatment in Chinese patients with DLBCL. Treatment-naive DLBCL patients who were CD20 positive and eligible to receive R-chemo were enrolled with no specific exclusion criteria. Data collected at baseline included age, gender, disease stage, international prognostic index (IPI), B symptoms, extranodal involvement, performance status, and medical history. In the present study, data on safety, treatment effectiveness, and HBV infection management were collected 120 days after the last R-chemo administration. Overall, R-chemo was well tolerated. The safety profile of R-chemo in patients with a history of heart or liver disease was well described without any additional unexpected safety concerns. The overall response rate (ORR) in the Chinese patients from this study was 94.2 % (complete response [CR], 55.0 %; CR unconfirmed [CRu] 18.2 %; and partial response [PR], 20.9 %). Compared to patients with no history of disease, the CR and PR rates of patients with a history of heart or liver disease were lower and higher, respectively; this tendency could be in part explained by treatment interruptions in patients with heart or liver diseases. HBsAg positivity and a maximum tumor diameter of ≥7.5 cm negatively correlated with CR + CRu, whereas age and HBsAg positivity negatively correlated with CR. This study further validated the safety and effectiveness of R-chemo in Chinese patients with DLBCL. Patients with a history of heart or liver disease may further benefit from R-chemo if preventive measures

  15. Gemcitabine and treatment of diffuse large B-cell lymphoma in relapsed or refractory elderly patients: A prospective randomized trial in Algeria

    Directory of Open Access Journals (Sweden)

    Aribi Mourad

    2010-01-01

    Full Text Available Context: Support for non-Hodgkin′s lymphoma (NHL with large cells that is refractory or relapsed after first-line chemotherapy poses a greater therapeutic problem with bone marrow transplant therapy or when old age is a contra-indication for high-dose chemotherapy, especially among developing countries such as Algeria. Aim: To show that the regimen, including gemcitabine, could be more effective in treating elderly patients with diffuse large B-cell lymphoma (DLBCL in relapse / refractory, without complete remission, when compared with the ESHAP (etoposide, cisplatine, solumedrol, aracytine regimen. Materials and Methods: Ninety-six patients in the age group of 60-70 years were volunteers for a prospective randomized single-blind study, carried out for three years. Patients were divided into two groups by the drawing of lots. The first group (GA, n = 48, relapse; n = 27 [56.3%], refractory; n = 21 [43.7%] received treatment with ESHAP protocol and the second one (GB, n = 48, relapse; n = 28 [58%], refractory; n = 20 [42%] with GPD (gemcitabine, dexamethasone, cisplatine protocol. Results: The overall response rates and mean survival at three years were significantly higher among patients subjected to GPD treatment compared with those subjected to ESHAP treatment (63% vs. 55%, P = 0.01 and 20.5% [95% CI 16.5-24.5] vs. 11.8% [8.9-14.6], respectively. Additionally, three-year progression-free and event-free survival rates were 20.5% (16.3-24 and 19.7% (15.9-23.5, respectively, for the GPD regimen and 10.9% (8.2-13.7 and 11.1% (95% CI 8.5-13.7, respectively, for the ESHAP regimen. Moreover, the GPD regimen was associated with improving overall survival (RR=2.02, 95% CI 1.59-2.56; P = 0.000, event-free survival (2.03, 1.64-2.52; P < 0.001 and progression-free survival (1.86, 1.46-2.37; P < 0.001. Conclusion: In cases of contra-indication for high-dose chemotherapy for elderly patients with DLBCL, without complete remission, the Gemcitabine

  16. Diffusion in molybdenum disilicide

    International Nuclear Information System (INIS)

    Salamon, M.; Mehrer, H.

    2005-01-01

    The diffusion behaviour of the high-temperature material molybdenum disilicide (MoSi 2 ) was completely unknown until recently. In this paper we present studies of Mo self-diffusion and compare our present results with our already published studies of Si and Ge diffusion in MoSi 2 . Self-diffusion of molybdenum in monocrystalline MoSi 2 was studied by the radiotracer technique using the radioisotope 99 Mo. Deposition of the radiotracer and serial sectioning after the diffusion anneals to determine the concentration-depth profiles was performed using a sputtering device. Diffusion of Mo is a very slow process. In the entire temperature region investigated (1437 to 2173 K), the 99 Mo diffusivities in both principal directions of the tetragonal MoSi 2 crystals obey Arrhenius laws, where the diffusion perpendicular to the tetragonal axis is faster by two to three orders of magnitude than parallel to it. The activation enthalpies for diffusion perpendicular and parallel to the tetragonal axis are Q perpendicular to = 468 kJ mol -1 (4.85 eV) and Q parallel = 586 kJ mol -1 (6.07 eV), respectively. Diffusion of Si and its homologous element Ge is fast and is mediated by thermal vacancies of the Si sublattice of MoSi 2 . The diffusion of Mo is by several orders of magnitude slower than the diffusion of Si and Ge. This large difference suggests that Si and Mo diffusion are decoupled and that the diffusion of Mo likely takes place via vacancies on the Mo sublattice. (orig.)

  17. Return to work for patients with diffuse large B-cell lymphoma and transformed indolent lymphoma undergoing autologous stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Arboe B

    2017-06-01

    Full Text Available Bente Arboe,1,2 Maja Halgren Olsen,2 Jette Soenderskov Goerloev,1 Anne Katrine Duun-Henriksen,2 Christoffer Johansen,2,3 Susanne Oksbjerg Dalton,2 Peter de Nully Brown1 1Department of Hematology, Copenhagen University Hospital, Rigshospitalet, 2Unit of Survivorship Research, The Danish Cancer Society Research Center, 3Department of Oncology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark Background: Autologous stem cell transplantation (ASCT is the standard treatment for patients with relapsed diffuse large B-cell lymphoma (DLBCL or transformed indolent lymphoma (TIL. The treatment is mainly considered for younger patients still available for the work market. In this study, social outcomes after ASCT in terms of return to work (RTW are described.Patients and methods: Information from national administrative registers was combined with clinical information on patients, who received ASCT for relapse of DLBCL or TIL between 2000 and 2012. A total of 164 patients were followed until RTW, disability or old-age pension, death, or December 31, 2015, whichever came first. A total of 205 patients were followed with disability pension as the event of interest. Cox models were used to determine cause-specific hazards. Results: During follow-up, 82 (50% patients returned to work. The rate of returning to work in the first year following ASCT was decreased for patients being on sick leave at the time of relapse (hazard ratio [HR] 0.3 [0.2;0.5] and increased for patients aged ≥55 years (HR 1.9 [1.1;3.3]. In all, 56 (27% patients were granted disability pension. Being on sick leave at the time of relapse was positively associated with receiving a disability pension in the first 2 years after ASCT (HR 3.7 [1.8;7.7]. Conclusion: Patients on sick leave at the time of relapse have a poorer prognosis regarding RTW and have a higher rate of disability pension. Furthermore, patients >55 are more likely to RTW compared to younger patients. These

  18. Intensity Modulated Radiation Therapy for Early-Stage Primary Gastric Diffuse Large B-Cell Lymphoma: Dosimetric Analysis, Clinical Outcome, and Quality of Life

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xin; Fang, Hui; Tian, Yuan; Wang, Wei-Hu; Song, Yong-Wen; Wang, Shu-Lian; Liu, Yue-Ping [Department of Radiation Oncology, Cancer Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing (China); He, Xiao-Hui; Dong, Mei [Department of Medical Oncology, Cancer Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing (China); Ren, Hua; Jin, Jing [Department of Radiation Oncology, Cancer Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing (China); Li, Ye-Xiong, E-mail: yexiong@yahoo.com [Department of Radiation Oncology, Cancer Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing (China)

    2016-06-01

    Purpose: To evaluate the dosimetric superiority, efficacy, toxicity, and quality of life (QOL) data of intensity modulated radiation therapy (IMRT) in patients with primary gastric diffuse large B-cell lymphoma (PG-DLBCL). Methods and Materials: Forty-six consecutive patients with early-stage PG-DLBCL underwent IMRT after chemotherapy. The majority of patients (61.5%) were subclassified as the non-germinal center B cell–like subtype. Dosimetric parameters of the planning target volume (PTV) and organs at risk were assessed. Survival rates were depicted with the Kaplan-Meier method and compared with the log-rank test. Quality of life was evaluated using the QLQ-C30-STO22 questionnaires at the last follow-up contact. Results: The median PTV mean dose was 41.6 Gy. Only 0.73% of the PTV received <95% of the prescribed dose, indicating excellent target coverage. The median kidney V20 and liver V30 were 14.1% and 16.1%, respectively. The 5-year overall survival (OS), progression-free survival, and locoregional control rates for all patients were 80.4%, 75.0%, and 93.2%, respectively. Stage, lactate dehydrogenase level, and immunophenotype were significant prognostic factors for OS, and only stage was a significant factor for locoregional control. Consolidation IMRT in patients with complete response after chemotherapy resulted in significantly better OS and progression-free survival than salvage IMRT in patients with non-complete response. Two of 8 patients who had chronic liver disease experienced grade 4 or grade 5 acute hepatic failure after 4 to 5 cycles of rituximab-based chemotherapy and IMRT (40 Gy). No other serious acute or late toxicity was observed. The long-term global and functional QOL scales were excellent, with negligible symptom scales. Conclusions: Intensity modulated radiation therapy yielded excellent target coverage and critical tissue sparing and achieved favorable outcomes with acceptable toxicity and good long-term QOL in early-stage PG-DLBCL.

  19. Molecular analysis of immunoglobulin variable genes supports a germinal center experienced normal counterpart in primary cutaneous diffuse large B-cell lymphoma, leg-type.

    Science.gov (United States)

    Pham-Ledard, Anne; Prochazkova-Carlotti, Martina; Deveza, Mélanie; Laforet, Marie-Pierre; Beylot-Barry, Marie; Vergier, Béatrice; Parrens, Marie; Feuillard, Jean; Merlio, Jean-Philippe; Gachard, Nathalie

    2017-11-01

    Immunophenotype of primary cutaneous diffuse large B-cell lymphoma, leg-type (PCLBCL-LT) suggests a germinal center-experienced B lymphocyte (BCL2+ MUM1+ BCL6+/-). As maturation history of B-cell is "imprinted" during B-cell development on the immunoglobulin gene sequence, we studied the structure and sequence of the variable part of the genes (IGHV, IGLV, IGKV), immunoglobulin surface expression and features of class switching in order to determine the PCLBCL-LT cell of origin. Clonality analysis with BIOMED2 protocol and VH leader primers was done on DNA extracted from frozen skin biopsies on retrospective samples from 14 patients. The clonal DNA IGHV sequence of the tumor was aligned and compared with the closest germline sequence and homology percentage was calculated. Superantigen binding sites were studied. Features of selection pressure were evaluated with the multinomial Lossos model. A functional monoclonal sequence was observed in 14 cases as determined for IGHV (10), IGLV (2) or IGKV (3). IGV mutation rates were high (>5%) in all cases but one (median:15.5%), with superantigen binding sites conservation. Features of selection pressure were identified in 11/12 interpretable cases, more frequently negative (75%) than positive (25%). Intraclonal variation was detected in 3 of 8 tumor specimens with a low rate of mutations. Surface immunoglobulin was an IgM in 12/12 cases. FISH analysis of IGHM locus, deleted during class switching, showed heterozygous IGHM gene deletion in half of cases. The genomic PCR analysis confirmed the deletions within the switch μ region. IGV sequences were highly mutated but functional, with negative features of selection pressure suggesting one or more germinal center passage(s) with somatic hypermutation, but superantigen (SpA) binding sites conservation. Genetic features of class switch were observed, but on the non functional allele and co-existing with primary isotype IgM expression. These data suggest that cell-of origin is

  20. NCCN-IPI score-independent prognostic potential of pretreatment uric acid levels for clinical outcome of diffuse large B-cell lymphoma patients

    Science.gov (United States)

    Prochazka, Katharina T; Melchardt, Thomas; Posch, Florian; Schlick, Konstantin; Deutsch, Alexander; Beham-Schmid, Christine; Weiss, Lukas; Gary, Thomas; Neureiter, Daniel; Klieser, Eckhard; Greil, Richard; Neumeister, Peter; Egle, Alexander; Pichler, Martin

    2016-01-01

    Background: Blood-based parameters are gaining increasing interest as potential prognostic biomarkers in patients with diffuse large B-cell lymphoma (DLBCL). The aim of this study was to comprehensively evaluate the prognostic significance of pretreatment plasma uric acid levels in patients with newly diagnosed DLBCL. Methods: The clinical course of 539 DLBCL patients, diagnosed and treated between 2004 and 2013 at two Austrian high-volume centres with rituximab-based immunochemotherapy was evaluated retrospectively. The prognostic influence of uric acid on overall survival (OS) and progression-free survival (PFS) were studied including multi-state modelling, and analysis of conditional survival. Results: Five-year OS and PFS were 50.4% (95% CI: 39.2–60.6) and 44.0% (33.4–54.0) in patients with uric acid levels above the 75th percentile of the uric acid distribution (Q3, cut-off: 6.8 mg dl−1), and 66.2% (60.4–71.5) and 59.6% (53.7–65.0%) in patients with lower levels (log-rank P=0.002 and P=0.0045, respectively). In univariable time-to-event analysis, elevated uric acid levels were associated with a worse PFS (hazard ratio (HR) per 1 log increase in uric acid 1.47, 95% CI: 1.10–1.97, P=0.009) and a worse OS (HR=1.60, 95% CI: 1.16–2.19, P=0.004). These associations prevailed upon multivariable adjustment for the NCCN-IPI score. Uric acid levels significantly improved the predictive performance of the R-IPI and NCCN-IPI scores, and in multi-state analysis, it emerged as a highly significant predictor of an increased risk of death without developing recurrence (transition-HR=4.47, 95% CI: 2.17–9.23, Puric acid levels predict poor long-term outcomes in DLBCL patients beyond the NCCN-IPI risk index. PMID:27764838

  1. Prognostic significance of metabolic tumor burden by positron emission tomography/computed tomography in patients with relapsed/refractory diffuse large B-cell lymphoma.

    Science.gov (United States)

    Tateishi, Ukihide; Tatsumi, Mitsuaki; Terauchi, Takashi; Ando, Kiyoshi; Niitsu, Nozomi; Kim, Won Seog; Suh, Cheolwon; Ogura, Michinori; Tobinai, Kensei

    2015-02-01

    The aim of the present study was to investigate the feasibility of measuring metabolic tumor burden using [F-18] fluorodeoxyglucose ((18) F-FDG) positron emission tomography/computed tomography (PET/CT) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) treated with bendamustine-rituximab. Because the standardized uptake value is a critical parameter of tumor characterization, we carried out a phantom study of (18) F-FDG PET/CT to ensure quality control for 28 machines in the 24 institutions (Japan, 17 institutions; Korea, 7 institutions) participating in our clinical study. Fifty-five patients with relapsed or refractory DLBCL were enrolled. The (18) F-FDG PET/CT was acquired before treatment, after two cycles, and after the last treatment cycle. Treatment response was assessed after two cycles and after the last cycle using the Lugano classification. Using this classification, remission was complete in 15 patients (27%) and incomplete in 40 patients (73%) after two cycles of therapy, and remission was complete in 32 patients (58%) and incomplete in 23 patients (42%) after the last treatment cycle. The percentage change in all PET/CT parameters except for the area under the curve of the cumulative standardized uptake value-volume histogram was significantly greater in complete response patients than in non-complete response patients after two cycles and the last cycle. The Cox proportional hazard model and best subset selection method revealed that the percentage change of the sum of total lesion glycolysis after the last cycle (relative risk, 5.24; P = 0.003) was an independent predictor of progression-free survival. The percent change of sum of total lesion glycolysis, calculated from PET/CT, can be used to quantify the response to treatment and can predict progression-free survival after the last treatment cycle in patients with relapsed or refractory DLBCL treated with bendamustine-rituximab. © 2014 The Authors. Cancer Science

  2. Prognostic impact of pre-transplantation computed tomography and 67gallium scanning in chemosensitive diffuse large B cell lymphoma patients undergoing hematopoietic stem-cell transplantation

    International Nuclear Information System (INIS)

    Escobar, Ignacio G.; Alonso, Pilar T.; Barrigon, Dolores C.; Perez-Simon, Jose A.; Mateos Manteca, Maria V.; San Miguel Izquierdo, Jesus F.

    2008-01-01

    In the present study, we evaluated computed tomography (CT) and 67 gallium scanning ( 67 Ga scan) pre-transplant as prognostic factors for overall survival (OS) and event-free survival (EFS) in patients with diffuse large B cell lymphoma, undergoing high-dose chemotherapy and stem-cell transplantation. Forty-two patients were included. Of these, 9 (21%) had both positive CT and 67 Ga scans, 17 (41%) negative results with both techniques, and 16 (38%) positive CT/negative 67 Ga scan. Whole-body planar imaging and single-photon emission computed tomography (SPECT) were performed 72 h after an intravenous administration of 67 Ga citrate measuring between 7 mCi and 10 mCi (259-370 MBq). Patients with positive CT/positive 67 Ga scan had a significantly worse EFS and OS at 5 years than those with negative 67 Ga scan regardless of whether it was associated with a positive or a negative CT scan (29% and 16% vs. 81% and 93% vs. 88% and 100%, respectively, P 67 Ga scan and those with positive CT/negative 67 Ga scan, with an EFS and OS at 5 years of 88% versus 81% and 100% versus 93%, respectively. In multivariate analysis, the presence of a pre-transplant positive CT/ 67 Ga scans adversely influenced both EFS and OS [HR 8, 95% confidence interval (CI) (1.4-38), P=0.03 and HR 2; 95% CI (1.3-8), P=0.02, respectively]. 67 Ga scan helps to identify, in the pre-transplant evaluation, two groups with a different outcome: one group of patients with positive CT and negative 67 Ga scans pre-transplant, who showed a favorable outcome with a low rate of relapse, and the other group of patients with both positive CT and 67 Ga scans pre-transplant, who showed a poor prognosis and did not benefit from autologous stem-cell transplantation. They should have been offered other therapeutic strategies. (author)

  3. Prognostic value of negative interim 2-["1"8F]-fluoro-2-deoxy-D-glucose PET/CT in diffuse large B-cell lymphoma

    International Nuclear Information System (INIS)

    Kwon, S.H.; Kang, D.R.; Kim, J.; Yoon, J.-K.; Lee, S.J.; Jeong, S.H.; Lee, H.W.; An, Y.-S.

    2016-01-01

    Aim: To assess the prognostic value of negative interim combined 2-["1"8F]-fluoro-2-deoxy-D-glucose ("1"8F-FDG) positron-emission tomography/computed tomography (PET/CT) in patients with diffuse large B-cell lymphoma (DLBCL). Materials and methods: Ninety-two patients with histologically proven DLBCL were enrolled. All of the patients underwent "1"8F-FDG PET/CT at diagnosis, and interim PET/CT after the second cycle of chemotherapy with rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisolone (R-CHOP). Negative interim PET/CT was defined as the disappearance of all abnormal "1"8F-FDG uptake compared to the pretreatment PET/CT image, as determined by visual assessment. The clinical outcome of patients was estimated as progression-free survival (PFS), and the prognostic significance of clinicopathological and imaging parameters were assessed using the Cox proportional hazards model. Results: Thirty-six patients (39.1%) showed lymphoma progression within a median follow-up of 30.8 months. According to univariate analysis, Ann Arbor stage, serum lactate dehydrogenase level, Eastern Cooperative Oncology Group scale, International Prognostic Index (IPI) score, and maximum standardised uptake values on initial PET/CT were significant prognostic factors for PFS (all p<0.05). Among these parameters, only the IPI score was an independent predictor for PFS (p=0.044). Survival of patients with a high IPI score (≥3) was poorer than those with a low IPI score (0–2; p<0.001). Conclusion: Despite a negative interim "1"8F-FDG PET/CT, approximately 39% of DLBCL patients showed progression during follow-up. Although the negative PET/CT was obtained during chemotherapy, it is important to closely follow-up patients, especially those with a high IPI score. - Highlights: • About 39% of patients showed progression after negative interim PET/CT. • The IPI score was an independent predictor for PFS. • It is important to closely follow-up with high IPI score

  4. Increased expression of IRF8 in tumor cells inhibits the generation of Th17 cells and predicts unfavorable survival of diffuse large B cell lymphoma patients.

    Science.gov (United States)

    Zhong, Weijie; Xu, Xin; Zhu, Zhigang; Du, Qinghua; Du, Hong; Yang, Li; Ling, Yanying; Xiong, Huabao; Li, Qingshan

    2017-07-25

    The immunological pathogenesis of diffuse large B cell lymphoma (DLBCL) remains elusive. Searching for new prognostic markers of DLBCL is a crucial focal point for clinical scientists. The aim of the present study was to examine the prognostic value of interferon regulatory factor 8 (IRF8) expression and its effect on the development of Th17 cells in the tumor microenvironment of DLBCL patients. Flow cytometry, immunohistochemistry, and quantitative real-time PCR were used to detect the distribution of Th17 cells and related cytokines and IRF8 in tumor tissues from DLBCL patients. Two DLBCL cell lines (OCI-LY10 and OCI-LY1) with IRF8 knockdown or overexpression and two human B lymphoblast cell lines were co-cultured with peripheral blood mononuclear cells (PBMCs) in vitro to determine the effect of IRF8 on the generation of Th17 cells. Quantitative real-time PCR and Western blotting were used to investigate the involvement of retinoic acid receptor-related orphan receptor gamma t (RORγt) in the effect of IRF8 on Th17 cell generation. The survival of 67 DLBCL patients was estimated using the Kaplan-Meier method and log-rank analysis. The percentage of Th17 cells was lower in DLBCL tumor tissues than in PBMCs and corresponding adjacent benign tissues. Relative expression of interleukin (IL)-17A was lower, whereas that of interferon (IFN)-γ was higher in tumor tissues than in benign tissues. Co-culture with DLBCL cell lines inhibited the generation of Th17 cells in vitro. IRF8 upregulation was detected in DLBCL tumor tissues, and it was associated with decreased DLBCL patient survival. Investigation of the underlying mechanism suggested that IRF8 upregulation in DLBCL, through an unknown mechanism, inhibited Th17 cell generation by suppressing RORγt in neighboring CD4+ T cells. Tumor cells may express soluble or membrane-bound factors that inhibit the expression of RORγt in T cells within the tumor microenvironment. Our findings suggest that IRF8 expression could

  5. Intensity Modulated Radiation Therapy for Early-Stage Primary Gastric Diffuse Large B-Cell Lymphoma: Dosimetric Analysis, Clinical Outcome, and Quality of Life

    International Nuclear Information System (INIS)

    Liu, Xin; Fang, Hui; Tian, Yuan; Wang, Wei-Hu; Song, Yong-Wen; Wang, Shu-Lian; Liu, Yue-Ping; He, Xiao-Hui; Dong, Mei; Ren, Hua; Jin, Jing; Li, Ye-Xiong

    2016-01-01

    Purpose: To evaluate the dosimetric superiority, efficacy, toxicity, and quality of life (QOL) data of intensity modulated radiation therapy (IMRT) in patients with primary gastric diffuse large B-cell lymphoma (PG-DLBCL). Methods and Materials: Forty-six consecutive patients with early-stage PG-DLBCL underwent IMRT after chemotherapy. The majority of patients (61.5%) were subclassified as the non-germinal center B cell–like subtype. Dosimetric parameters of the planning target volume (PTV) and organs at risk were assessed. Survival rates were depicted with the Kaplan-Meier method and compared with the log-rank test. Quality of life was evaluated using the QLQ-C30-STO22 questionnaires at the last follow-up contact. Results: The median PTV mean dose was 41.6 Gy. Only 0.73% of the PTV received <95% of the prescribed dose, indicating excellent target coverage. The median kidney V20 and liver V30 were 14.1% and 16.1%, respectively. The 5-year overall survival (OS), progression-free survival, and locoregional control rates for all patients were 80.4%, 75.0%, and 93.2%, respectively. Stage, lactate dehydrogenase level, and immunophenotype were significant prognostic factors for OS, and only stage was a significant factor for locoregional control. Consolidation IMRT in patients with complete response after chemotherapy resulted in significantly better OS and progression-free survival than salvage IMRT in patients with non-complete response. Two of 8 patients who had chronic liver disease experienced grade 4 or grade 5 acute hepatic failure after 4 to 5 cycles of rituximab-based chemotherapy and IMRT (40 Gy). No other serious acute or late toxicity was observed. The long-term global and functional QOL scales were excellent, with negligible symptom scales. Conclusions: Intensity modulated radiation therapy yielded excellent target coverage and critical tissue sparing and achieved favorable outcomes with acceptable toxicity and good long-term QOL in early-stage PG-DLBCL.

  6. Circulating CXCR5+CD4+ T cells assist in the survival and growth of primary diffuse large B cell lymphoma cells through interleukin 10 pathway

    Energy Technology Data Exchange (ETDEWEB)

    Cha, Zhanshan [Department of Transfusion, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China); Qian, Guangfang [Department of Endocrinology, Zhangqiu Municipal Hospital of Traditional Chinese Medicine, Zhangqiu, Shandong 250200 (China); Zang, Yan; Gu, Haihui; Huang, Yanyan; Zhu, Lishuang; Li, Jinqi; Liu, Yang; Tu, Xiaohua [Department of Transfusion, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China); Song, Haihan [Emergency Center, East Hospital, Shanghai 200120 (China); Qian, Baohua, E-mail: qianbhl963@163.com [Department of Transfusion, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China)

    2017-01-01

    Diffuse large B cell lymphoma (DLBCL) is a common and aggressive cancer caused by the malignant transformation of B cells. Although it has been established that the follicular helper T (Tfh) cells play a central role in B cell development, little information is available on their involvement in DLBCL pathogenesis. We studied the role of the peripheral Tfh equivalent, the CXCR5{sup +} CD4{sup +} T cells, in DLBCL. Data showed that compared to CXCR5{sup -} CD4{sup +} T cells, CXCR5{sup +} CD4{sup +} T cells were significantly more effective at promoting the proliferation as well as inhibiting the apoptosis of primary autologous DLBCL tumor cells. Surprisingly, we found that at equal cell numbers, CXCR5{sup +} CD4{sup +} T cells in DLBCL patients secreted significantly less interleukin (IL)-21 than CXCR5{sup -} CD4{sup +} T cells, while the level of IL-10 secretion was significant elevated in the CXCR5{sup +} compartment compared to the CXCR5{sup -} compartment. Neutralization of IL-10 in the primary DLBCL-CXCR5{sup +} CD4{sup +} T cell coculture compromised the CXCR5{sup +} CD4{sup +} T cell-mediated pro-tumor effects, in a manner that was dependent on the concentration of anti-IL-10 antibodies. The CXCR5{sup +} compartment also contained significantly lower frequencies of cytotoxic CD4{sup +} T cells than the CXCR5{sup -} compartment. In conclusion, our investigations discovered a previously unknown pro-tumor role of CXCR5-expressing circulating CD4{sup +} T cells, which assisted the survival and proliferation of primary DLBCL cells through IL-10. - Highlights: • We studied the role of the peripheral Tfh in DLBCL. • Tfh were effective at promoting the proliferation of primary DLBCL tumor cells. • Tfh were effective at inhibiting the apoptosis of primary DLBCL tumor cells. • IL-10 secretion in Tfh was significant elevated in DLBCL. • Neutralization of IL-10 compromised Tfh-mediated pro-tumor effects.

  7. Real world costs and cost-effectiveness of Rituximab for diffuse large B-cell lymphoma patients: a population-based analysis.

    Science.gov (United States)

    Khor, Sara; Beca, Jaclyn; Krahn, Murray; Hodgson, David; Lee, Linda; Crump, Michael; Bremner, Karen E; Luo, Jin; Mamdani, Muhammad; Bell, Chaim M; Sawka, Carol; Gavura, Scott; Sullivan, Terrence; Trudeau, Maureen; Peacock, Stuart; Hoch, Jeffrey S

    2014-08-12

    Current treatment of diffuse-large-B-cell lymphoma (DLBCL) includes rituximab, an expensive drug, combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy. Economic models have predicted rituximab plus CHOP (RCHOP) to be a cost-effective alternative to CHOP alone as first-line treatment of DLBCL, but it remains unclear what its real-world costs and cost-effectiveness are in routine clinical practice. We performed a population-based retrospective cohort study from 1997 to 2007, using linked administrative databases in Ontario, Canada, to evaluate the costs and cost-effectiveness of RCHOP compared to CHOP alone. A historical control cohort (n = 1,099) with DLBCL who received CHOP before rituximab approval was hard-matched on age and treatment intensity and then propensity-score matched on sex, comorbidity, and histology to 1,099 RCHOP patients. All costs and outcomes were adjusted for censoring using the inverse probability weighting method. The main outcome measure was incremental cost per life-year gained (LYG). Rituximab was associated with a life expectancy increase of 3.2 months over 5 years at an additional cost of $16,298, corresponding to an incremental cost-effectiveness ratio of $61,984 (95% CI $34,087-$135,890) per LYG. The probability of being cost-effective was 90% if the willingness-to-pay threshold was $100,000/LYG. The cost-effectiveness ratio was most favourable for patients less than 60 years old ($31,800/LYG) but increased to $80,600/LYG for patients 60-79 years old and $110,100/LYG for patients ≥ 80 years old. We found that post-market survival benefits of rituximab are similar to or lower than those reported in clinical trials, while the costs, incremental costs and cost-effectiveness ratios are higher than in published economic models and differ by age. Our results showed that the addition of rituximab to standard CHOP chemotherapy was associated with improvement in survival but at a higher cost, and was

  8. Experimental study of the possibility of reducing the resistance and unevenness of output field of velocities in flat diffuser channels with large opening angles

    Science.gov (United States)

    Dmitriev, S. S.; Vasil'ev, K. E.; Mokhamed, S. M. S. O.; Gusev, A. A.; Barbashin, A. V.

    2017-11-01

    In modern combined cycle gas turbines (CCGT), when designing the reducers from the output diffuser of a gas turbine to a boiler-utilizer, wide-angle diffusers are used, in which practically from the input a flow separation and transition to jet stream regime occurs. In such channels, the energy loss in the field of velocities sharply rise and the field of velocities in the output from them is characterized by considerable unevenness that worsens the heat transfer process in the first by motion tube bundles of the boiler-utilizer. The results of experimental research of the method for reducing the energy loss and alignment of the field of velocities at the output from a flat asymmetrical diffuser channel with one deflecting wall with the opening angle of 40° by means of placing inside the channel the flat plate parallel to the deflecting wall are presented in the paper. It is revealed that, at this placement of the plate in the channel, it has a chance to reduce the energy loss by 20%, considerably align the output field of velocities, and decrease the dynamic loads on the walls in the output cross-section. The studied method of resistance reduction and alignment of the fields of velocities in the flat diffuser channels was used for optimization of the reducer from the output diffuser of the gas turbine to the boiler-utilizer of CCGT of PGU-450T type of Kaliningrad Thermal Power Plant-2. The obtained results are evidence that the configuration of the reducer installed in the PGU-450T of Kaliningrad Thermal Power Plant-2 is not optimal. It follows also from the obtained data that working-off the reducer should be necessarily conducted by the test results of the channel consisting of the model of reducer with the model of boiler-utilizer installed behind it. Application of the method of alignment of output field of velocities and reducing the resistance in the wide-angle diffusers investigated in the work made it possible—when using the known model of diffusion

  9. Th1/2 Immune Response Signature Predicts Outcome after Dose-Dense Immunochemotherapy in Patients with High Risk Diffuse Large B-Cell Lymphoma – Results from Nordic Lymphoma Group Trials

    DEFF Research Database (Denmark)

    M, Autio; Jørgensen, Judit Meszaros; SK, Leivonen

    treatment-specific roles in diffuse large B-cell lymphoma. For the high risk DLBCL patients treated with dose-dense immunochemotherapy, high expression of type 1/2 immune response signature genes predicts a poor outcome. A detailed characterization of immune cell composition in the tumor microenvironment......Introduction: Despite better therapeutic options and improved survival of diffuse large B-cell lymphoma (DLBCL), 30-40% of the patients still relapse and have dismal prognosis. Recently, the impact of genomic aberrations, allowing lymphoma cells to escape immune recognition on DLBCL pathogenesis...... has been recognized. However, whether immune related signatures could be used as determinants for treatment outcome has not been rigorously evaluated. Here, our aim was to elucidate the immunologic characteristics of the tumor microenvironment, and associate the findings with outcome in patients...

  10. Primary central nervous system diffuse large B-cell lymphoma shows an activated B-cell-like phenotype with co-expression of C-MYC, BCL-2, and BCL-6.

    Science.gov (United States)

    Li, Xiaomei; Huang, Ying; Bi, Chengfeng; Yuan, Ji; He, Hong; Zhang, Hong; Yu, QiuBo; Fu, Kai; Li, Dan

    2017-06-01

    Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma, whose main prognostic factor is closely related to germinal center B-cell-like subtype (GCB- DLBCL) or activated B-cell-like type (non-GCB-DLBCL). The most common type of primary central nervous system lymphoma is diffuse large B-cell type with poor prognosis and the reason is unclear. This study aims to stratify primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL) according to the cell-of-origin (COO) and to investigate the multiple proteins expression of C-MYC, BCL-6, BCL-2, TP53, further to elucidate the reason why primary central nervous system diffuse large B-cell lymphoma possesses a poor clinical outcome as well. Nineteen cases of primary central nervous system DLBCL were stratified according to immunostaining algorithms of Hans, Choi and Meyer (Tally) and we investigated the multiple proteins expression of C-MYC, BCL-6, BCL-2, TP53. The Epstein-Barr virus and Borna disease virus infection were also detected. Among nineteen cases, most (15-17 cases) were assigned to the activated B-cell-like subtype, highly expression of C-MYC (15 cases, 78.9%), BCL-2 (10 cases, 52.6%), BCL-6 (15 cases, 78.9%). Unfortunately, two cases were positive for PD-L1 while PD-L2 was not expressed in any case. Two cases infected with BDV but no one infected with EBV. In conclusion, most primary central nervous system DLBCLs show an activated B-cell-like subtype characteristic and have multiple expressions of C-MYC, BCL-2, BCL-6 protein, these features might be significant factor to predict the outcome and guide treatment of PCNS-DLBCLs. Copyright © 2017 Elsevier GmbH. All rights reserved.

  11. Fractional diffusion equations and anomalous diffusion

    CERN Document Server

    Evangelista, Luiz Roberto

    2018-01-01

    Anomalous diffusion has been detected in a wide variety of scenarios, from fractal media, systems with memory, transport processes in porous media, to fluctuations of financial markets, tumour growth, and complex fluids. Providing a contemporary treatment of this process, this book examines the recent literature on anomalous diffusion and covers a rich class of problems in which surface effects are important, offering detailed mathematical tools of usual and fractional calculus for a wide audience of scientists and graduate students in physics, mathematics, chemistry and engineering. Including the basic mathematical tools needed to understand the rules for operating with the fractional derivatives and fractional differential equations, this self-contained text presents the possibility of using fractional diffusion equations with anomalous diffusion phenomena to propose powerful mathematical models for a large variety of fundamental and practical problems in a fast-growing field of research.

  12. HASA/DOD Aerospace Knowledge Diffusion Research Project. Paper 62. The Influence of Knowledge Diffusion on Aeronautics Innovation: The Research, Development, and Production of Large Commercial Aircraft in France, Germany, and the United Kingdom

    National Research Council Canada - National Science Library

    Golich, Vicki

    1997-01-01

    ...) of large commercial aircraft (LCA). The analytical framework brings together literature from global political economy, comparative politics, business management, and science and technology policy studies...

  13. Atomic diffusion in stars

    CERN Document Server

    Michaud, Georges; Richer, Jacques

    2015-01-01

    This book gives an overview of atomic diffusion, a fundamental physical process, as applied to all types of stars, from the main sequence to neutron stars. The superficial abundances of stars as well as their evolution can be significantly affected. The authors show where atomic diffusion plays an essential role and how it can be implemented in modelling.  In Part I, the authors describe the tools that are required to include atomic diffusion in models of stellar interiors and atmospheres. An important role is played by the gradient of partial radiative pressure, or radiative acceleration, which is usually neglected in stellar evolution. In Part II, the authors systematically review the contribution of atomic diffusion to each evolutionary step. The dominant effects of atomic diffusion are accompanied by more subtle effects on a large number of structural properties throughout evolution. One of the goals of this book is to provide the means for the astrophysicist or graduate student to evaluate the importanc...

  14. Conservative diffusions

    International Nuclear Information System (INIS)

    Carlen, E.A.

    1984-01-01

    In Nelson's stochastic mechanics, quantum phenomena are described in terms of diffusions instead of wave functions. These diffusions are formally given by stochastic differential equations with extremely singular coefficients. Using PDE methods, we prove the existence of solutions. This reult provides a rigorous basis for stochastic mechanics. (orig.)

  15. Measuring methods of matrix diffusion

    International Nuclear Information System (INIS)

    Muurinen, A.; Valkiainen, M.

    1988-03-01

    In Finland the spent nuclear fuel is planned to be disposed of at large depths in crystalline bedrock. The radionuclides which are dissolved in the groundwater may be able to diffuse into the micropores of the porous rock matrix and thus be withdrawn from the flowing water in the fractures. This phenomenon is called matrix diffusion. A review over matrix diffusion is presented in the study. The main interest is directed to the diffusion of non-sorbing species. The review covers diffusion experiments and measurements of porosity, pore size, specific surface area and water permeability

  16. Synergistic effect of oridonin and a PI3K/mTOR inhibitor on the non-germinal center B cell-like subtype of diffuse large B cell lymphoma

    Directory of Open Access Journals (Sweden)

    Kai Qing

    2016-08-01

    Full Text Available Abstract We demonstrate the synergistic antitumor effect of oridonin and the PI3K/mTOR inhibitor NVP-BEZ235 on the non-germinal center B cell-like subtype of diffuse large B cell lymphoma (non-GCB DLBCL both in vitro and in vivo. The underlying mechanism may be multifunctional, involving apoptosis, AKT/mTOR and NF-kB inactivation, and ROS-mediated DNA damage response. Our findings pave the way for a new potential treatment option for non-GCB DLBCL with the combination of oridonin and NVP-BEZ235.

  17. Prognostic impact of clinician-based interpretation of 18F-fluorodeoxyglucose positron emission tomography/computed tomography reports obtained in patients with newly diagnosed diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Mylam, Karen J; El-Galaly, Tarec C; Hutchings, Martin

    2014-01-01

    The aim of this study was to evaluate the prognostic value of clinician interpretation of positron emission tomography/computed tomography (PET/CT) reports at mid-therapy, interim PET (I-PET) and after the end of first-line therapy (E-PET) in patients with diffuse large B-cell lymphoma (DLBCL.......001) for positive, indeterminate and negative interpretation of PET/CT reports. Progression-free survival and OS did not differ significantly in patients with a negative and an indeterminate I-PET report. The use of well-defined reporting criteria, e.g. the Deauville five-point scale, is likely to reduce the number...

  18. Real world data on young patients with high-risk diffuse large B-cell lymphoma treated with R-CHOP or R-CHOEP - MYC, BCL2 and BCL6 as prognostic biomarkers

    DEFF Research Database (Denmark)

    Pedersen, Mette Ølgod; Gang, Anne Ortved; Brown, Peter

    2017-01-01

    BACKGROUND: Double expression of MYC and BCL2 proteins (DE) and double-hit MYC+BCL2/BCL6 translocations (DH) were established as important biomarkers in patients with diffuse large B-cell lymphoma (DLBCL) by the 2016 revision of the World Health Organization classification of lymphoid neoplasms...... in situ hybridization (FISH). RESULTS: DE with MYC>75% and BCL2>85% was an independent negative prognostic marker of progression free survival (PFS) in patients treated with R-CHOP but not R-CHOEP (peffect of DE for response (PFS) to R...

  19. Highly conformal SiO2/Al2O3 nanolaminate gas-diffusion barriers for large-area flexible electronics applications

    International Nuclear Information System (INIS)

    Choi, Jin-Hwan; Kim, Young-Min; Park, Young-Wook; Park, Tae-Hyun; Jeong, Jin-Wook; Choi, Hyun-Ju; Song, Eun-Ho; Ju, Byeong-Kwon; Lee, Jin-Woo; Kim, Cheol-Ho

    2010-01-01

    The present study demonstrates a flexible gas-diffusion barrier film, containing an SiO 2 /Al 2 O 3 nanolaminate on a plastic substrate. Highly uniform and conformal coatings can be made by alternating the exposure of a flexible polyethersulfone surface to vapors of SiO 2 and Al 2 O 3 , at nanoscale thickness cycles via RF-magnetron sputtering deposition. The calcium degradation test indicates that 24 cycles of a 10/10 nm inorganic bilayer, top-coated by UV-cured resin, greatly enhance the barrier performance, with a permeation rate of 3.79 x 10 -5 g m -2 day -1 based on the change in the ohmic behavior of the calcium sensor at 20 deg. C and 50% relative humidity. Also, the permeation rate for 30 cycles of an 8/8 nm inorganic bilayer coated with UV resin was beyond the limited measurable range of the Ca test at 60 deg. C and 95% relative humidity. It has been found that such laminate films can effectively suppress the void defects of a single inorganic layer, and are significantly less sensitive against moisture permeation. This nanostructure, fabricated by an RF-sputtering process at room temperature, is verified as being useful for highly water-sensitive organic electronics fabricated on plastic substrates.

  20. Left ventricular rigid body rotation in a diffuse large B-cell lymphoma patient with cardiac involvement: A case from the three-dimensional speckle-tracking echocardiographic MAGYAR-Path Study.

    Science.gov (United States)

    Földeák, Dóra; Kalapos, Anita; Domsik, Péter; Sinkó, Mária; Szeleczki, Nóra; Bagdi, Enikő; Krenács, László; Forster, Tamás; Borbényi, Zita; Nemes, Attila

    2017-02-01

    Secondary myocardial involvement by diffuse large B-cell lymphoma is a rare occurrence. Left ventricular (LV) twist is considered an essential part of LV function. In normal circumstances LV twist results from the movement of two orthogonally oriented muscular bands of a helical myocardial structure with consequent clockwise rotation of the base and counterclockwise rotation of the apex. Three-dimensional (3D) speckle-tracking echocardiography (3DSTE) has been found to be feasible for non-invasive 3D quantification of LV wall motion and rotational mechanics. The present report aimed to assess LV twisting motion in a patient with diffuse large B-cell lymphoma with positron emission tomography/computer tomography-proven cardiac involvement by 3DSTE. During 3DSTE, reduction in some segmental radial, longitudinal, circumferential, area and 3D LV strains were found. Apical and basal LV rotations were found to be in the same counterclockwise direction, confirming near absence of LV twist - so-called rigid body rotation. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

  1. Diffuse Ceiling Ventilation

    DEFF Research Database (Denmark)

    Zhang, Chen; Heiselberg, Per; Nielsen, Peter V.

    2014-01-01

    As a novel air distribution system, diffuse ceiling ventilation combines the suspended acoustic ceiling with ventilation supply. Due to the low-impulse supply from the large ceiling area, the system does not generate draught when supplying cold air. However, heat sources play an important role...

  2. Fractional Diffusion Equations and Anomalous Diffusion

    Science.gov (United States)

    Evangelista, Luiz Roberto; Kaminski Lenzi, Ervin

    2018-01-01

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

  3. Primary Diffuse Large B-Cell Lymphoma in a Patient with Rubinstein-Taybi Syndrome: Case Report and Review of the Literature.

    Science.gov (United States)

    Sy, Christopher; Henry, James; Kura, Bhavani; Brenner, Andrew; Grandhi, Ramesh

    2018-01-01

    Rubinstein-Taybi syndrome (RSTS) is a rare, congenital syndrome that is known to be associated with neoplasms of various organ systems. Evaluation and treatment of such patients is challenging, given the cognitive delay and heterogeneity of pathologic presentations that define this syndrome. Presented here is a case of a patient with RSTS, diagnosed at birth, who presented with subtle symptoms of lethargy and a change in behavior. He was found to have a large (7.0-cm × 4.7-cm), right-sided brain mass that was eventually diagnosed as a primary central nervous system lymphoma. To the best of our knowledge, this is the first reported case of a primary central nervous system lymphoma presenting in a patient with RSTS. This was confirmed through microscopic and histologic studies. The large size attained by this mass in our patient highlights the increased scrutiny and surveillance needed to provide the best care for these patients. A multidisciplinary team approach is ideal as successful treatment of our patient using surgical debulking, appropriate chemotherapy, and close postoperative follow-up has resulted in an excellent clinical outcome. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Osmosis and Diffusion Conceptual Assessment

    Science.gov (United States)

    Fisher, Kathleen M.; Williams, Kathy S.; Lineback, Jennifer Evarts

    2011-01-01

    Biology student mastery regarding the mechanisms of diffusion and osmosis is difficult to achieve. To monitor comprehension of these processes among students at a large public university, we developed and validated an 18-item Osmosis and Diffusion Conceptual Assessment (ODCA). This assessment includes two-tiered items, some adopted or modified…

  5. PI3Kδ inhibitor idelalisib in combination with BTK inhibitor ONO/GS-4059 in diffuse large B cell lymphoma with acquired resistance to PI3Kδ and BTK inhibitors.

    Directory of Open Access Journals (Sweden)

    Anella Yahiaoui

    Full Text Available Activated B-cell-like diffuse large B-cell lymphoma relies on B-cell receptor signaling to drive proliferation and survival. Downstream of the B-cell receptor, the key signaling kinases Bruton's tyrosine kinase and phosphoinositide 3-kinase δ offer opportunities for therapeutic intervention by agents such as ibrutinib, ONO/GS-4059, and idelalisib. Combination therapy with such targeted agents could provide enhanced efficacy due to complimentary mechanisms of action. In this study, we describe both the additive interaction of and resistance mechanisms to idelalisib and ONO/GS-4059 in a model of activated B-cell-like diffuse large B-cell lymphoma. Significant tumor regression was observed with a combination of PI3Kδ and Bruton's tyrosine kinase inhibitors in the mouse TMD8 xenograft. Acquired resistance to idelalisib in the TMD8 cell line occurred by loss of phosphatase and tensin homolog and phosphoinositide 3-kinase pathway upregulation, but not by mutation of PIK3CD. Sensitivity to idelalisib could be restored by combining idelalisib and ONO/GS-4059. Further evaluation of targeted inhibitors revealed that the combination of idelalisib and the phosphoinositide-dependent kinase-1 inhibitor GSK2334470 or the AKT inhibitor MK-2206 could partially overcome resistance. Characterization of acquired Bruton's tyrosine kinase inhibitor resistance revealed a novel tumor necrosis factor alpha induced protein 3 mutation (TNFAIP3 Q143*, which led to a loss of A20 protein, and increased p-IκBα. The combination of idelalisib and ONO/GS-4059 partially restored sensitivity in this resistant line. Additionally, a mutation in Bruton's tyrosine kinase at C481F was identified as a mechanism of resistance. The combination activity observed with idelalisib and ONO/GS-4059, taken together with the ability to overcome resistance, could lead to a new therapeutic option in activated B-cell-like diffuse large B-cell lymphoma. A clinical trial is currently underway to

  6. An International Collaborative Study of Outcome and Prognostic Factors in Patients with Secondary CNS Involvement By Diffuse Large B-Cell Lymphoma

    DEFF Research Database (Denmark)

    El-Galaly, Tarec Christoffer; Cheah, Chan Yoon; Bendtsen, Mette Dahl

    2016-01-01

    that develop SCNS following primary therapy that contains a rituximab-based-regimen as well as the impact of more intensified treatment for SCNS are limited.Aims: The aims of this study were to i) describe the natural history of SCNS in a large cohort of patients treated with immunochemotherapy, and ii......' Hospital, London). Clinico-pathologic and treatment characteristics at the time of SCNS were collected from medical records.Results: In total, 281 patients with SCNS diagnosed between 2001 and 2016 were included. Median age at SCNS was 64 (range 20-93) years and male:female ratio was 1.3. SCNS occurred...... Myers Squib: Research Funding; NanoString Technologies: Research Funding; F Hoffmann-La Roche: Research Funding; Millennium Takeda: Research Funding; Seattle Genetics: Research Funding. Sehn: roche/genentech: Consultancy, Honoraria; amgen: Consultancy, Honoraria; seattle genetics: Consultancy, Honoraria...

  7. Primary Type3 (Non-ABC, Non-GCB Subtype of Extranodal Diffuse Large B-Cell Lymphoma of the Thyroid Bearing No MYD88 Mutation by Padlock Probe Hybridization

    Directory of Open Access Journals (Sweden)

    Yukiko Nishi

    2017-06-01

    Full Text Available Primary extranodal malignant lymphoma of the thyroid is a rare entity composed of mostly neoplastic transformation of germinal center-like B cells (GCB or memory B cells. Other B-cell-type malignancies arising primarily in the thyroid have rarely been described. Immunohistochemical examination of autopsied primary malignant lymphoma of the thyroid in an 83-year-old Japanese female revealed the presence of a non-GCB subtype of diffuse large B-cell lymphoma (DLBCL without the typical codon 206 or 265 missense mutation of MYD88. The lack of the highly oncogenic MYD88 gene mutation, frequently observed in DLBCL of the activated B-cell (ABC subtype, and the detection of an extremely aggressive yet local clinical phenotype demonstrated that the present case was an exceptional entity of the type3 (non-GCB and non-ABC subtype.

  8. Positron Emission Tomography/Computed Tomography Findings During Therapy Predict Outcome in Patients With Diffuse Large B-Cell Lymphoma Treated With Chemotherapy Alone but Not in Those Who Receive Consolidation Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Dabaja, Bouthaina S., E-mail: bdabaja@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Hess, Kenneth [Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Shihadeh, Ferial [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Podoloff, Donald A. [Department of Nuclear Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Medeiros, L. Jeffrey [Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mawlawi, Osama [Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Arzu, Isidora [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Oki, Yasuhiro; Hagemeister, Fredrick B.; Fayad, Luis E. [Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Reed, Valerie K.; Kedir, Aziza; Wogan, Christine F. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Rodriguez, Alma [Office of the Executive Vice President and Physician-in-Chief, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2014-06-01

    Purpose: To assess the value of mid-therapy positron emission tomography (PET) findings for predicting survival and disease progression in patients with diffuse large B-cell lymphoma, considering type of therapy (chemotherapy with or without radiation therapy). Methods and Materials: We retrospectively evaluated 294 patients with histologically confirmed diffuse large B-cell lymphoma with respect to age, sex, disease stage, International Prognostic Index score, mid-therapy PET findings (positive or negative), and disease status after therapy and at last follow-up. Overall survival (OS) and progression-free survival (PFS) were compared according to mid-therapy PET findings. Results: Of the 294 patients, 163 (55%) were male, 144 (49%) were age >61 years, 110 (37%) had stage I or II disease, 219 (74%) had International Prognostic Index score ≤2, 216 (73%) received ≥6 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, and 88 (30%) received consolidation radiation therapy. Five-year PFS and OS rates were associated with mid-therapy PET status: PFS was 78% for those with PET-negative (PET−) disease versus 63% for PET-positive (PET+) disease (P=.024), and OS was 82% for PET− versus 62% for PET+ (P<.002). These associations held true for patients who received chemotherapy only (PFS 71% for PET− vs 52% PET+ [P=.012], OS 78% for PET− and 51% for PET+ [P=.0055]) but not for those who received consolidation radiation therapy (PFS 84% PET− vs 81% PET+ [P=.88]; OS 90% PET− vs 81% PET+ [P=.39]). Conclusion: Mid-therapy PET can predict patient outcome, but the use of consolidation radiation therapy may negate the significance of mid-therapy findings.

  9. Primary EBV-positive Hodgkin's lymphoma of the CNS under azathioprine treatment. Case report and review of the literature

    International Nuclear Information System (INIS)

    Henkenberens, Christoph; Christiansen, Hans; Franzke, Anke; Raab, Peter; Oschlies, Ilske; Klapper, Wolfram

    2014-01-01

    Retrospective and prospective cohort studies suggest that central nervous system involvement occurs in approximately 0.5 % of patients with advanced Hodgkin's lymphoma. The isolated primary intracranial manifestation of Hodgkin's lymphoma is an extremely rare finding, with few cases reported in the literature. Little is known about the optimal treatment and prognosis of these tumors. Here, we present a case report with a review of the literature. A 47-year-old Caucasian man with persistent frontal headache and unspecific vertigo for half a month was diagnosed with nodular space-occupying lesions in the cerebellum. His medical history included multiple sclerosis, which was treated for 20 years with the immunosuppressive drug azathioprine. Further staging revealed no additional lesions suspected of being malignant. The patient underwent total tumor resection. Immunohistopathological examination showed Epstein-Barr virus-associated classic Hodgkin's lymphoma. Diagnostic bone marrow punction excluded lymphoma involvement of the bone marrow. The patient had no B symptoms. Consequently, the patient was classified as having stage I E A disease according to the Modified Ann Arbor Classification of Hodgkin Lymphoma and received systemic chemotherapy followed by radiation therapy for the former cerebellar tumor region. He was in complete clinical remission at the last follow-up 9 months after the initial diagnosis. This case report and literature review suggest that multimodal treatment leads to a remarkable clinical outcome in Hodgkin's lymphoma with intracranial involvement. (orig.) [de

  10. Composite Lymphoma : EBV-positive Classic Hodgkin Lymphoma and Peripheral T-cell Lymphoma A Case Report

    NARCIS (Netherlands)

    Gualco, Gabriela; Chioato, Lucimara; Van Den Berg, Anke; Weiss, Lawrence M.; Bacchi, Carlos E.

    Composite lymphomas are rare and defined as hematopoietic neoplasms with more than I malignant lymphomatous clone showing different phenotypic features. Of all possible combinations between non-Hodgkin lymphomas, B cell or T cell, and Hodgkin lymphoma, the least frequent are the ones combining

  11. Human pathogenic Mycoplasma species induced cytokine gene expression in Epstein-Barr virus (EBV)-positive lymphoblastoid cell lines.

    Science.gov (United States)

    Schäffner, E; Opitz, O; Pietsch, K; Bauer, G; Ehlers, S; Jacobs, E

    1998-04-01

    We addressed the question whether the in vitro interaction of two Epstein-Barr virus (EBV)-genome-positive B cell lines (EB-3 and HilB-gamma) with either Mycoplasma pneumoniae or M. hominis, with the mycoplasma species (M. fermentans, M. fermentans subsp. incognitus, M. penetrans, M. genitalium) or with mycoplasma species known to be mere commensals of the respiratory tract (M. orale and M. salivarium) would result in expression of mRNAs for IL-2, IL-2R, IL-4 and IL-6 as determined by reverse transcriptase (RT)-PCR after 4 and 24 h of cocultivation. The pattern of cytokine gene expression observed depended on (i) the origin of the transformed cell line, (ii) the pathogenicity of the Mycoplasma species, and (iii) the length of cocultivation. The EBV-immortalized lymphoblastoid cell line HilB-gamma showed mRNA expression for IL-2, IL-2-receptor, IL-4 and IL-6 peaking 24 h after stimulation with M. pneumoniae and all AIDS-related mycoplasma species tested. The Burkitt lymphoma cell line EB-3 showed a distinct and isolated strong II-2/IL-2 R-mRNA expression within 4 h after contact with the pathogenic and all of the AIDS related mycoplasma species. In neither EBV-containing cell line cytokine was gene expression detectable after stimulation with the commensal mycoplasma species, M. orale and M. salivarium, indicating species differences in the ability of mycoplasmas to interact with and stimulate B-cell lines. Our data suggest that some mcyoplasma species may act as immunomodulatory cofactors by eliciting inappropriate cytokine gene expression in B cells latently infected with EBV. Therefore, this cultivation model may prove useful in evaluating the pathogenetic potential of novel isolated mycoplasma species. Copyright 1998 Academic Press Limited.

  12. Diffusion bonding

    International Nuclear Information System (INIS)

    Anderson, R.C.

    1976-01-01

    A method is described for joining beryllium to beryllium by diffusion bonding. At least one surface portion of at least two beryllium pieces is coated with nickel. A coated surface portion is positioned in a contiguous relationship with another surface portion and subjected to an environment having an atmosphere at a pressure lower than ambient pressure. A force is applied on the beryllium pieces for causing the contiguous surface portions to abut against each other. The contiguous surface portions are heated to a maximum temperature less than the melting temperature of the beryllium, and the applied force is decreased while increasing the temperature after attaining a temperature substantially above room temperature. A portion of the applied force is maintained at a temperature corresponding to about maximum temperature for a duration sufficient to effect the diffusion bond between the contiguous surface portions

  13. Multipassage diffuser

    International Nuclear Information System (INIS)

    Lalis, A.; Rouviere, R.; Simon, G.

    1976-01-01

    A multipassage diffuser having 2p passages comprises a leak-tight cylindrical enclosure closed by a top cover and a bottom end-wall, parallel porous tubes which are rigidly assembled in sectors between tube plates and through which the gas mixture flows, the tube sectors being disposed at uniform intervals on the periphery of the enclosure. The top tube plates are rigidly fixed to an annular header having the shape of a half-torus and adapted to communicate with the tubes of the corresponding sector. Each passage is constituted by a plurality of juxtaposed sectors in which the mixture circulates in the same direction, the header being divided into p portions limited by radial partition-walls and each constituting two adjacent passages. The diffuser is provided beneath the bottom end-wall with p-1 leak-tight chambers each adapted to open into two different portions of the header, and with two collector-chambers each fitted with a nozzle for introducing the gas mixture and discharging the fraction of the undiffused mixture. By means of a central orifice formed in the bottom end-wall the enclosure communicates with a shaft for discharging the diffused fraction of the gas mixture

  14. Constitutive activation of alternative nuclear factor kappa B pathway in canine diffuse large B-cell lymphoma contributes to tumor cell survival and is a target of new adjuvant therapies.

    Science.gov (United States)

    Seelig, Davis M; Ito, Daisuke; Forster, Colleen L; Yoon, Una A; Breen, Matthew; Burns, Linda J; Bachanova, Veronika; Lindblad-Toh, Kerstin; O'Brien, Timothy D; Schmechel, Stephen C; Rizzardi, Anthony E; Modiano, Jaime F; Linden, Michael A

    2017-07-01

    Activation of the classical nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) pathway is a common molecular event observed in both human and canine diffuse large B-cell lymphoma (DLBCL). Although the oncogenic potential of the alternative NFκB pathway (ANFκBP) has also been recently identified in DLBCL, its precise role in tumor pathogenesis and potential as a treatment target is understudied. We hypothesized that up-regulation of the ANFκBP plays an important role in the proliferation and survival of canine DLBCL cells, and we demonstrate that the ANFκBP is constitutively active in primary canine DLBCL samples and a cell line (CLBL1). We further demonstrate that a small interfering RNA inhibits the activation of the NFκB pathway and induces apoptosis in canine DLBCL cells. In conclusion, the ANFκBP facilitates survival of canine DLBCL cells, and thus, dogs with spontaneous DLBCL can provide a useful large animal model to study therapies targeting the ANFκBP.

  15. Diffusion of condenser water discharge

    International Nuclear Information System (INIS)

    Iwakiri, Toshio

    1977-01-01

    Thermal and nuclear power stations in Japan are mostly located in coastal area, and the cooling water is discharged into sea as warm water. Recently, large interest is taken in this matter, and it is desirable to predict the diffusion of warm discharge accurately and to take effective measures for lowering the temperature. As for the methods of predicting the diffusion of warm discharge, simplified estimation, mathematical analysis and hydrographical model experiment are used corresponding to objects and conditions. As for the measures to lower temperature, the method of discharging warm water into deep sea bottom was confirmed to be very effective. In this paper, the phenomena of diffusion of warm discharge in sea, the methods of predicting the diffusion of warm discharge, and the deep sea discharge as the measure for lowering temperature are outlined. The factors concerning the diffusion of warm discharge in sea are the conditions of discharge, topography and sea state, and the diffusion is roughly divided into mixing diffusion in the vicinity of warm water outlet and eddy diffusion in distant region. It is difficult to change artificially the conditions of diffusion in distant region, and the measures of raising the rate of dilution in near region are effective, therefore the deep sea discharge is adopted. (Kako, I.)

  16. Quantum diffusion

    International Nuclear Information System (INIS)

    Habib, S.

    1994-01-01

    We consider a simple quantum system subjected to a classical random force. Under certain conditions it is shown that the noise-averaged Wigner function of the system follows an integro-differential stochastic Liouville equation. In the simple case of polynomial noise-couplings this equation reduces to a generalized Fokker-Planck form. With nonlinear noise injection new ''quantum diffusion'' terms rise that have no counterpart in the classical case. Two special examples that are not of a Fokker-Planck form are discussed: the first with a localized noise source and the other with a spatially modulated noise source

  17. Hereditary Diffuse Gastric Cancer

    Science.gov (United States)

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

  18. The Trouble with Diffusion

    Directory of Open Access Journals (Sweden)

    R.T. DeHoff

    2002-09-01

    Full Text Available The phenomenological formalism, which yields Fick's Laws for diffusion in single phase multicomponent systems, is widely accepted as the basis for the mathematical description of diffusion. This paper focuses on problems associated with this formalism. This mode of description of the process is cumbersome, defining as it does matrices of interdiffusion coefficients (the central material properties that require a large experimental investment for their evaluation in three component systems, and, indeed cannot be evaluated for systems with more than three components. It is also argued that the physical meaning of the numerical values of these properties with respect to the atom motions in the system remains unknown. The attempt to understand the physical content of the diffusion coefficients in the phenomenological formalism has been the central fundamental problem in the theory of diffusion in crystalline alloys. The observation by Kirkendall that the crystal lattice moves during diffusion led Darken to develop the concept of intrinsic diffusion, i.e., atom motion relative to the crystal lattice. Darken and his successors sought to relate the diffusion coefficients computed for intrinsic fluxes to those obtained from the motion of radioactive tracers in chemically homogeneous samples which directly report the jump frequencies of the atoms as a function of composition and temperature. This theoretical connection between tracer, intrinsic and interdiffusion behavior would provide the basis for understanding the physical content of interdiffusion coefficients. Definitive tests of the resulting theoretical connection have been carried out for a number of binary systems for which all three kinds of observations are available. In a number of systems predictions of intrinsic coefficients from tracer data do not agree with measured values although predictions of interdiffusion coefficients appear to give reasonable agreement. Thus, the complete

  19. Large deviations

    CERN Document Server

    Varadhan, S R S

    2016-01-01

    The theory of large deviations deals with rates at which probabilities of certain events decay as a natural parameter in the problem varies. This book, which is based on a graduate course on large deviations at the Courant Institute, focuses on three concrete sets of examples: (i) diffusions with small noise and the exit problem, (ii) large time behavior of Markov processes and their connection to the Feynman-Kac formula and the related large deviation behavior of the number of distinct sites visited by a random walk, and (iii) interacting particle systems, their scaling limits, and large deviations from their expected limits. For the most part the examples are worked out in detail, and in the process the subject of large deviations is developed. The book will give the reader a flavor of how large deviation theory can help in problems that are not posed directly in terms of large deviations. The reader is assumed to have some familiarity with probability, Markov processes, and interacting particle systems.

  20. Localized primary gastrointestinal diffuse large B cell lymphoma received a surgical approach: an analysis of prognostic factors and comparison of staging systems in 101 patients from a single institution.

    Science.gov (United States)

    Zhang, Shengting; Wang, Li; Yu, Dong; Shen, Yang; Cheng, Shu; Zhang, Li; Qian, Ying; Shen, Zhixiang; Li, Qinyu; Zhao, Weili

    2015-08-15

    Diffuse large B cell lymphoma (DLBCL) represents the most common histological subtype of primary gastrointestinal lymphoma and is a heterogeneous group of disease. Prognostic characterization of individual patients is an essential prerequisite for a proper risk-based therapeutic choice. Clinical and pathological prognostic factors were identified, and predictive value of four previously described prognostic systems were assessed in 101 primary gastrointestinal DLBCL (PG-DLBCL) patients with localized disease, including Ann Arbor staging with Musshoff modification, International Prognostic Index (IPI), Lugano classification, and Paris staging system. Univariate factors correlated with inferior survival time were clinical parameters [age>60 years old, multiple extranodal/gastrointestinal involvement, elevated serum lactate dehydrogenase and β2-microglobulin, and decreased serum albumin], as well as pathological parameters (invasion depth beyond serosa, involvement of regional lymph node or adjacent tissue, Ki-67 index, and Bcl-2 expression). Major independent variables of adverse outcome indicated by multivariate analysis were multiple gastrointestinal involvement. In patients unfit for Rituximab but received surgery, radical surgery significantly prolonged the survival time, comparing with alleviative surgery. Addition of Rituximab could overcome the negative prognostic effect of alleviative surgery. Among the four prognostic systems, IPI and Lugano classification clearly separated patients into different risk groups. IPI was able to further stratify the early-stage patients of Lugano classification into groups with distinct prognosis. Radical surgery might be proposed for the patients unfit for Rituximab treatment, and a combination of clinical and pathological staging systems was more helpful to predict the disease outcome of PG-DLBCL patients.

  1. Change of CD20 Expression in Diffuse Large B-Cell Lymphoma Treated with Rituximab, an Anti-CD20 Monoclonal Antibody: A Study of the Osaka Lymphoma Study Group

    Directory of Open Access Journals (Sweden)

    Naoki Wada

    2009-10-01

    Full Text Available Change of CD20 expression was examined in cases of diffuse large B-cell lymphoma (DLBCL. CD20 expression after treatment with anti-CD20 antibody (rituximab, Rx for DLBCL was examined in 23 cases who received serial biopsy by immunohistochemistry (IHC and flow cytometry (FCM. CD20– by IHC and/or FCM was defined as CD20–. Four cases were CD20– at initial biopsy but became CD20+ after chemotherapy with Rx (CH-R (group A. Recurrent tumors in three group A cases became resistant to CH-R. Initial and recurrent tumors were CD20+ before and after CH-R in 17 cases (group B. Tumors before CH-R were CD20– in two cases (group C and continued to be CD20– in one and turned CD20+ in the other with survival time after the relapse of 8 and 23 months, respectively. Evaluation of CD20 expression with immunohistochemical and flow cytometric methods is used for the prediction of responsiveness of relapsed DLBCL for CH-R.

  2. MicroRNAs are suitable for assessment as biomarkers from formalin-fixed paraffin-embedded tissue, and miR-24 represents an appropriate reference microRNA for diffuse large B-cell lymphoma studies.

    Science.gov (United States)

    Culpin, Rachel Emily; Sieniawski, Michal; Proctor, Stephen John; Menon, Geetha; Mainou-Fowler, Tryfonia

    2013-03-01

    Tissue biopsy specimens in the form of formalin-fixed paraffin-embedded tissue (FFPET) represent a valuable resource for biomarker identification and validation. However, to date, they remain an underused asset due to uncertainty regarding RNA extraction and the reliability of downstream techniques, including quantitative RT-PCR. Recently, much interest has emerged in the study of microRNAs; small single-stranded RNAs with a role in transcriptional regulation, that are thought to be well preserved in FFPET. In this study, we show that microRNA expression is comparable between FFPET and matched fresh-frozen samples (miR-17-5p: p=0.01, miR-92: p=0.003), and demonstrate that no significant deterioration in expression occurs over prolonged FFPET storage (p=0.06). Furthermore, microRNA expression is equivalent dependant on RNA extraction method (p<0.001) or DNAse treatment of total RNA (p<0.001). Finally, we validate miR-24 as a suitable reference microRNA for diffuse large B-cell lymphoma (DLBCL) FFPET studies.

  3. Learning from the failures of drug discovery in B-cell non-Hodgkin lymphomas and perspectives for the future: chronic lymphocytic leukemia and diffuse large B-cell lymphoma as two ends of a spectrum in drug development.

    Science.gov (United States)

    Kubuschok, Boris; Trepel, Martin

    2017-07-01

    Despite substantial recent advances, there is still an unmet need for better therapies in B-cell non Hodgkin lymphomas (B-NHL), especially in relapsed or refractory disease. Many novel targeted drugs have been developed based on a better molecular understanding of B-NHL. Areas covered: This article focuses on chronic lymphocytic leukemia (CLL) as a representative for indolent lymphomas and paradigmatic for the tremendous progress in treating B-NHL on the one hand and diffuse large B-cell lymphoma (DLBCL) as a representative for aggressive lymphomas and paradigmatic for many unsolved problems in lymphoma treatment or the other hand. We highlight salient points in current therapies targeting genetic, epigenetic, immunological and microenvironmental alterations. Possible reasons for drug failure in clinical trials like tumor heterogeneity, clonal evolution and drug resistance mechanisms are discussed. Based thereon, some perspectives for further drug discovery are given. Expert opinion: In view of the pathogenetic complexity of lymphomas, therapies targeting exclusively a single alteration may fail because resistance mechanisms are present either initially or evolve during treatment. Therefore, future therapies in B-NHL may have to target the greatest possible number of genetic, immunological or epigenetic alterations still allowing tolerability and to monitor these alterations during therapy.

  4. Secondary cutaneous Epstein-Barr virus-associated diffuse large B-cell lymphoma in a patient with angioimmunoblastic T-cell lymphoma: a case report and review of literature

    Directory of Open Access Journals (Sweden)

    Yang Qing-Xu

    2012-01-01

    Full Text Available Abstract Only a few cases of extranodal Epstein-Barr virus (EBV-associated B-cell lymphomas arising from patients with angioimmunoblastic T-cell lymphoma (AITL have been described. We report a case of AITL of which secondary cutaneous EBV-associated diffuse large B-cell lymphoma (DLBCL developed after the initial diagnosis of AITL. A 65-year-old Chinese male patient was diagnosed as AITL based on typical histological and immunohistochemical characteristics in biopsy of the enlarged right inguinal lymph nodes. The patient initially received 6 cycles of chemotherapy with CHOP regimen (cyclophosphamide, vincristine, adriamycin, prednisone, but his symptoms did not disappear. Nineteen months after initial diagnosis of AITL, the patient was hospitalized again because of multiple plaques and nodules on the skin. The skin biopsy was performed, but this time the tumor was composed of large, polymorphous population of lymphocytes with CD20 and CD79a positive on immunohistochemical staining. The tumor cells were strong positive for EBER by in situ hybridization. The findings of skin biopsy were compatible with EBV-associated DLBCL. CHOP-R chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab was then administered, resulting in partial response of the disease with pancytopenia and suppression of cellular immunity. To our knowledge, this is the first case of cutaneous EBV-associated DLBCL originated from AITL in Chinese pepole. We suggest the patients with AITL should perform lymph node and skin biopsies regularly in the course of the disease to detect the progression of secondary lymphomas. Virtual slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1197421158639299

  5. MDM2 gene SNP309 T/G and p53 gene SNP72 G/C do not influence diffuse large B-cell non-Hodgkin lymphoma onset or survival in central European Caucasians

    Directory of Open Access Journals (Sweden)

    Landt Olfert

    2008-04-01

    Full Text Available Abstract Background SNP309 T/G (rs2279744 causes higher levels of MDM2, the most important negative regulator of the p53 tumor suppressor. SNP72 G/C (rs1042522 gives rise to a p53 protein with a greatly reduced capacity to induce apoptosis. Both polymorphisms have been implicated in cancer. The SNP309 G-allele has recently been reported to accelerate diffuse large B-cell lymphoma (DLBCL formation in pre-menopausal women and suggested to constitute a genetic basis for estrogen affecting human tumorigenesis. Here we asked whether SNP309 and SNP72 are associated with DLBCL in women and are correlated with age of onset, diagnosis, or patient's survival. Methods SNP309 and SNP72 were PCR-genotyped in a case-control study that included 512 controls and 311 patients diagnosed with aggressive NHL. Of these, 205 were diagnosed with DLBCL. Results The age of onset was similar in men and women. The control and patients group showed similar SNP309 and SNP72 genotype frequencies. Importantly and in contrast to the previous findings, similar genotype frequencies were observed in female patients diagnosed by 51 years of age and those diagnosed later. Specifically, 3/20 female DLBCL patients diagnosed by 51 years of age were homozygous for SNP309 G and 2/20 DLBCL females in that age group were homozygous for SNP72 C. Neither SNP309 nor SNP72 had a significant influence on event-free and overall survival in multivariate analyses. Conclusion In contrast to the previous study on Ashkenazi Jewish Caucasians, DLBCL in pre-menopausal women of central European Caucasian ethnicity was not associated with SNP309 G. Neither SNP309 nor SNP72 seem to be correlated with age of onset, diagnosis, or survival of patients.

  6. miR expression in MYC-negative DLBCL/BL with partial trisomy 11 is similar to classical Burkitt lymphoma and different from diffuse large B-cell lymphoma.

    Science.gov (United States)

    Zajdel, Michalina; Rymkiewicz, Grzegorz; Chechlinska, Magdalena; Blachnio, Katarzyna; Pienkowska-Grela, Barbara; Grygalewicz, Beata; Goryca, Krzysztof; Cieslikowska, Maria; Bystydzienski, Zbigniew; Swoboda, Pawel; Walewski, Jan; Siwicki, Jan Konrad

    2015-07-01

    Fast and reliable differential diagnosis of Burkitt lymphoma (BL) vs. diffuse large B cell lymphoma (DLBCL) is of major importance for therapeutic decisions and patient outcome. Aggressive B cell non-Hodgkin lymphomas (B-NHLs) that do not belong to the abovementioned entities were categorized by the current WHO lymphoma classification as "B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and BL" (DLBCL/BL). We have recently described a DLBCL/BL subgroup with recurrent chromosome 11q aberrations, resembling BL (B-NHLs[11q]). Here, we analyzed 102 prospectively collected fine needle aspirates from patients with aggressive B-NHLs in order to investigate the potential of microRNA (miR)-155, its precursor BIC, as well as miR-21 and miR-26a to differentiate BL from DLBCL, and from DLBCL/BL that include B-NHLs[11q]. Both BL and DLBCL/BL cases, including B-NHLs[11q], demonstrated significantly lower expression levels of miR-155/BIC, miR-21, and miR-26a compared to primary DLBCL. In conclusion, the miRs expression in B-NHLs[11q] provides a new suggestion, in addition to pathomorphological and clinical similarities between classical, i.e., MYC translocation-positive BL, and B-NHLs[11q], to recognize the B-NHLs[11q] subgroup of DLBCL/BL category as a MYC translocation-negative variant of BL in most cases, and points to the potential utility of miR-155/BIC/miR-21/miR-26a for the differential diagnosis of a heterogeneous category of DLBCL/BL.

  7. Discovery and validation of the tumor-suppressive function of long noncoding RNA PANDA in human diffuse large B-cell lymphoma through the inactivation of MAPK/ERK signaling pathway.

    Science.gov (United States)

    Wang, Yingjun; Zhang, Mingzhi; Xu, Huanan; Wang, Yifei; Li, Zhaoming; Chang, Yu; Wang, Xinhuan; Fu, Xiaorui; Zhou, Zhiyuan; Yang, Siyuan; Wang, Bei; Shang, Yufeng

    2017-09-22

    Diffuse large B-cell lymphoma (DLBCL) is one of the leading causes of cancer-related mortality, and responds badly to existing treatment. Thus, it is of urgent need to identify novel prognostic markers and therapeutic targets of DLBCL. Recent studies have shown that long non-coding RNAs (lncRNAs) play an important role in the development of cancer. By using the next generation HiSeq sequencing assay, we determined lncRNAs exhibiting differential expression between DLBCL patients and healthy controls. Then, RT-qPCR was performed for identification in clinical samples and cell materials, and lncRNA PANDA was verified to be down-regulated in DLBCL patients and have considerable diagnostic potential. In addition, decreased serum PANDA level was correlated to poorer clinical outcome and lower overall survival in DLBCL patients. Subsequently, we determined the experimental role of lncRNA PANDA in DLBCL progression. Luciferase reporter assay and chromatin immunoprecipitation assay suggested that lncRNA PANDA was induced by p53 and p53 interacts with the promoter region of PANDA. Cell functional assay further indicated that PANDA functioned as a tumor suppressor gene through the suppression of cell growth by a G0/G1 cell cycle arrest in DLBCL. More importantly, Cignal Signal Transduction Reporter Array and western blot assay showed that lncRNA PANDA inactivated the MAPK/ERK signaling pathway. In conclusion, our integrated approach demonstrates that PANDA in DLBCL confers a tumor suppressive function through inhibiting cell proliferation and silencing MAPK/ERK signaling pathway. Thus, PANDA may be a promising therapeutic target for patients with DLBCL.

  8. Prevalence and chemotherapy-induced reactivation of occult hepatitis B virus among hepatitis B surface antigen negative patients with diffuse large B-cell lymphoma: Significance of hepatitis B core antibodies screening

    International Nuclear Information System (INIS)

    Elbedewy, T.A.; Elashtokhy, H.A.; Rabee, E.S.; Kheder, G.E.

    2015-01-01

    Background: Occult hepatitis B infection (OBI) is characterized by negative hepatitis B surface antigen (HBsAg) and detectable hepatitis B virus (HBV)-DNA in the liver and/or serum, with or without hepatitis B core antibody (anti-HBc). Anti-HBc is the most sensitive marker of previous HBV. HBV reactivation in patients under immunosuppressive treatment is life-threatening, occurring in both overt and occult HBV especially in hematological malignancies. Aim of the work: To evaluate the prevalence and chemotherapy-induced reactivation of OBI among hepatitis B surface antigen negative patients with diffuse large B-cell lymphoma (DLBCL) patients and to determine the significance of anti-HBc screening among this group of patients before receiving chemotherapy. Patients and methods: This cross-sectional study included 72 DLBCL patients negative for HBsAg, HBsAb and hepatitis C virus antibodies (anti-HCV). Patients were subjected to investigations including anti-HBc. All patients underwent alanine transaminase (ALT) monitoring before each cycle of chemotherapy and monthly for 12 months after the end of chemotherapy. Patients with suspected OBI were tested for HBV-DNA using real-time polymerase chain reaction (PCR). Results: Anti-HBc was detected in 10 of 72 HBsAg negative sera (13.89%) (95% confidence interval 6.9-22.2%). Five of the 10 anti-HBc positive patients in this study had OBI reactivation. Conclusion: The study concluded that anti-HBc screening is mandatory before chemotherapy. HBsAg-negative/anti-HBc-positive patients should be closely observed for signs of HBV reactivation through the regular monitoring of ALT. Prophylaxis lamivudine is recommended for anti-HBc positive patients before chemotherapy.

  9. Standardized uptake value for (18)F-fluorodeoxyglucose is correlated with a high International Prognostic Index and the presence of extranodal involvement in patients with diffuse large B-cell lymphoma.

    Science.gov (United States)

    Akkas, B E; Vural, G U

    2014-01-01

    The aim of this study was to evaluate whether the maximum standardized uptake value (SUVmax) of (18)F-fluorodeoxyglucose (FDG) correlates with the International Prognostic Index (IPI) and the presence of extranodal involvement in patients with Diffuse Large B-Cell Lymphoma (DLBCL). 77 patients (age: 57.2±18.5, 40F, 37M) with DLBCL who underwent FDG PET/CT for initial staging were included. SUVmax of the predominant lesions were compared to Ann Arbor stage, IPI scores, the presence of extranodal involvement and the number extranodal sites. PET/CT detected nodal (n:25) and extranodal involvement (n:52) in all the patients. In 27 patients, extranodal disease could only be detected by PET. SUVmax of the predominant lesion in patients with extranodal disease was significantly higher than that of the patients who had only nodal disease (25±12 vs. 15.3±10 respectively, p=0.001). SUVmax significantly correlated with IPI scores; the average SUVmax was significantly correlated with the IPI: Mean SUVmax of the predominant lesion was 13.9±9.5 in patients with low risk (IPI=0-1), 14.2±8.8 in low-intermediate risk group (IPI=2) whereas 26.6±9.5 in high-intermediate risk group (IPI=3) and 25±13.6 in high risk group patients (IPI=4-5) (p=0.002). SUVmax was not correlated with clinical stage, the number of extranodal sites and serum LDH levels. FDG uptake correlates with IPI and the presence of extranodal involvement in DLBCL. PET is a powerful method to detect extranodal disease in DLBCL. The correlation of SUVmax with these prognostic factors may highlight the importance of pretreatment FDG uptake as a metabolic marker of poor prognosis for patients with DLBCL. Copyright © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.

  10. Evaluation of diffuse large B-cell lymphoma patients with 64-slice multidetector computed tomography versus 18FDG positron emission tomography/computed tomography in initial staging and restaging after treatment.

    Science.gov (United States)

    Gómez León, Nieves; Vega, Gema; Rodríguez-Vigil Junco, Beatriz; Suevos Ballesteros, Carlos

    2018-04-25

    To prospectively compare the accuracy in initial staging and end-of-treatment restaging of diffuse large B-cell lymphoma (DLBCL) between 64-slice multidetector computed tomography (64MDCT) and 18FDG positron emission tomography/computed tomography (18FGD PET/CT) with intravenous contrast injection. Randomised and blind controlled clinical multicentric trial that included biopsy-proven DLBCL patients. Seventy-two patients from five different hospitals in the region of Madrid, Spain, were enrolled in the study between January 2012 and June 2015. Thirty-six were randomly allocated to 18FDG PET/TC and the other 36 to 64MDCT for initial staging and end-of-treatment restaging. A nuclear medicine physician and a radiologist independently analysed 18FDG PET/TC images and reached an agreement post-hoc. 64MDCT images were separately evaluated by a different radiologist. Every set of images was compared to the reference standard that included clinical data, complementary tests and follow-up. The study was approved by participating centres' ethics committees and written informed consent was obtained from all the participants. A good agreement was observed between both diagnostic techniques and the reference standard in initial staging [18FDG PET/CT (k=0.5) and 64MDCT (k=0.6)], although only the 18FDG PET/TC showed a good agreement with the reference standard for the end-of-treatment restaging (k=0.7). In DLBCL, both 18FDG PET/TC and 64MDCT have shown good agreement with the reference standard in initial staging. Nevertheless, 18FDG PET/CT has shown to be superior to 64MDCT in end-of-treatment response assessment. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

  11. Immunohistochemical Expression of CD-10, BCL-6 and MUM-1 Antibodies and Immediate Clinical Response in Patients of Diffuse Large B-Cell Lymphomas after Six Cycles of Chemotherapy

    International Nuclear Information System (INIS)

    Hassan, U.; Ishtiaq, S.; Hussain, M.

    2014-01-01

    Objective: To determine the expression of CD-10, BCL-6 and MUM-1 in patients with diffuse large B-cell lymphoma (DLBCL) and its association with immediate clinical response after six cycles of CHOP chemotherapy. Study Design: Analytical study. Place and Duration of Study: Armed Forces Institute of Pathology (AFIP), Rawalpindi in collaboration with Nuclear medicine, Oncology and Radiotherapy Institute (NORI), Islamabad from September 2010 to September 2011. Methodology: CD-10, BCL-6 and MUM-1 antibodies were applied on cases diagnosed as DLBCL. Immediate clinical response was noted after 6 cycles of chemotherapy with the help of oncologist and divided into complete response, partial response, stable disease and relapse/ progression. Patient's age, results of expression of CD-10, BCL-6 and MUM-1 and results of immediate clinical response to chemotherapy were noted. Regarding analysis of prognostic markers (CD-10, BCL-6 and MUM-1), chi-square test was used for immediate clinical response to chemotherapy in DLBCL. Results: CD-10 was positive in 40% cases, BCL-6 in 58.7% cases and MUM-1 was positive in 46.7% cases. About 41.3% of patients showed complete response, 10.6% partial response, 17.3% stable disease and 30.8% showed relapse/progression. CD-10 expression in DLBCL was associated with better immediate clinical response (p = 0.011) whereas MUM-1 expression in DLBCL was associated with poor immediate clinical response (p < 0.0001). However, there was no statistically significant association of BCL-6 with immediate clinical response (p = 0.22). Conclusion: DLBCL shows expression of CD-10, BCL-6 and MUM-1 in nearly fifty percent of the cases. CD-10 is associated with good whereas MUM is associated with poor response. However, there was no association of BCL-6 with immediate clinical response. (author)

  12. Real world data on young patients with high-risk diffuse large B-cell lymphoma treated with R-CHOP or R-CHOEP - MYC, BCL2 and BCL6 as prognostic biomarkers.

    Directory of Open Access Journals (Sweden)

    Mette Ølgod Pedersen

    Full Text Available Double expression of MYC and BCL2 proteins (DE and double-hit MYC+BCL2/BCL6 translocations (DH were established as important biomarkers in patients with diffuse large B-cell lymphoma (DLBCL by the 2016 revision of the World Health Organization classification of lymphoid neoplasms. Whether this applies to the subgroup of young patients with high risk DLBCL is not known. We previously found that in a uniform retrospective population-based cohort of patients aged 18-60 years with high-risk DLBCL, the addition of etoposide to R-CHOP chemotherapy (R-CHOEP resulted in improved survival mainly in patients with germinal center B-cell like (GCB immunophenotype. The aim of this study was to investigate the prognostic and predictive value of DE and DH in this patient cohort.Data on all young Danish patients diagnosed with de novo high-risk DLBCL 2004-2008 and treated with R-CHOP or R-CHOEP were obtained from the Danish Lymphoma database (n = 159. Tumor samples were available from 103 patients. MYC and BCL2 proteins were analyzed with quantitative immunohistochemistry (IHC using different cut off values. MYC-, BCL2- and BCL6-translocations were examined with fluorescent in situ hybridization (FISH.DE with MYC>75% and BCL2>85% was an independent negative prognostic marker of progression free survival (PFS in patients treated with R-CHOP but not R-CHOEP (p<0.001, also after exclusion of patients with DH. A predictive effect of DE for response (PFS to R-CHOEP vs. R-CHOP was almost significant (p = 0.07. DH was not prognostic in this patient cohort.In young patients with high-risk DLBCL, treatment with R-CHOEP may overcome the negative prognostic impact of DE observed in patients treated with R-CHOP.

  13. Methodology of clinical trials evaluating the incorporation of new drugs in the first-line treatment of patients with diffuse large B-cell lymphoma (DLBCL): a critical review.

    Science.gov (United States)

    Iacoboni, G; Zucca, E; Ghielmini, M; Stathis, A

    2018-05-01

    The first-line treatment of diffuse large B-cell lymphoma (DLBCL) is the combination of rituximab with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy, curing approximately 60% of patients. Many clinical trials have been carried out over the last 10 years trying to improve the results of this treatment, but the appropriateness of their planning strategies could be rediscussed. Reports of phase III trials evaluating the addition of molecularly targeted agents or new monoclonal antibodies to the classic R-CHOP backbone in first-line induction or maintenance treatment were reviewed. The trial design, primary end point, number of patients enrolled, patient selection criteria, treatment schedule and results were registered for each one. In addition, the phases I and II trials which preceded these phase III trials were also reviewed. Among six phase III trials with results, only one trial evaluating lenalidomide maintenance after response to R-CHOP induction was positive and reached its primary end point. The other five trials did not show an improved outcome with the addition of the new agent. The preceding phases I and II trials were very heterogeneous in their end points and design. Even though most of these trials were considered positive, thus encouraging further investigation, so far they failed to predict the results of the subsequent phase III trials. The standard of care for DLBCL is still R-CHOP. Phase I/II trials failed to predict the results of subsequent phase III trials evaluating non-chemotherapeutic agents added to R-CHOP. The methodology of phase II trials evaluating new agents in DLBCL needs to be better defined in the future.

  14. A salvage chemotherapy of R-P-IMVP16/CBDCA consisting of rituximab, methylprednisolone, ifosfamide, methotrexate, etoposide, and carboplatin for patients with diffuse large B cell lymphoma who had previously received R-CHOP therapy as first-line chemotherapy.

    Science.gov (United States)

    Matsumoto, Takuro; Hara, Takeshi; Shibata, Yuhei; Nakamura, Nobuhiko; Nakamura, Hiroshi; Ninomiya, Soranobu; Kitagawa, Junichi; Kanemura, Nobuhiro; Goto, Naoe; Kito, Yusuke; Kasahara, Senji; Yamada, Toshiki; Sawada, Michio; Miyazaki, Tatsuhiko; Takami, Tsuyoshi; Takeuchi, Tamotsu; Moriwaki, Hisataka; Tsurumi, Hisashi

    2017-09-01

    We have reported the efficacy of the salvage chemotherapy P-IMVP16/CBDCA for patients with diffuse large B cell lymphoma (DLBCL) who had previously received CHOP before the availability of rituximab (R). Here, we confirmed the efficacy of R combined with P-IMVP16/CBDCA as a salvage chemotherapy for patients with DLBCL, who had previously received R-CHOP. We retrospectively analysed 59 patients with relapse or refractory DLBCL (38 male patients and 21 female patients) presenting between June 2004 and June 2013. The patients received R 375 mg/m 2 on day 1, methylprednisolone 1000 mg/body for 3 days (from day 3 to day 5), ifosfamide 1000 mg/m 2 for 5 days (from day 3 to day 7), methotrexate 30 mg/m 2 on day 5 and day 12, etoposide 80 mg/m 2 for 3 days (from day 3 to day 5), and carboplatin 300 mg/m 2 on day 3 every 21 days. Patients aged 70 years or older were given 75% of the standard dose. The overall response rate (complete response + partial response) was 64.4%. The 2-year overall survival rate was 55.3%. The 2-year progression free survival rate was 34.7%. The 2-year overall survival rate was 61.5% for the relapse patients, and 15.6% for the refractory patients (p effects were mild and tolerable. The R-P-IMVP-16/CBDCA regimen displayed a significant activity in relapsed DLBCL, with acceptable toxicity, and should be considered a candidate for salvage chemotherapy. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  15. Impact of high-dose chemotherapy and autologous transplantation as first-line therapy on the survival of high-risk diffuse large B cell lymphoma patients: a single-center study in Japan.

    Science.gov (United States)

    Inano, Shojiro; Iwasaki, Makoto; Iwamoto, Yoshihiro; Sueki, Yuki; Fukunaga, Akiko; Yanagita, Soshi; Arima, Nobuyoshi

    2014-02-01

    High-dose chemotherapy (HDT), together with autologous stem cell transplantation (ASCT), plays an important role in the treatment of diffuse large B cell lymphoma (DLBCL), especially as second-line therapy. However, its significance in up-front settings remains to be elucidated. In our institute, patients with DLBCL in both the high-intermediate and high international prognostic index (IPI) groups initially underwent CHOP/R-CHOP treatment followed by HDT/ASCT at upfront settings between 2002 and 2011. We retrospectively analyzed 25 patients who were all treated with upfront HDT/ASCT. We excluded one patient who failed to undergo transplantation because of primary refractory disease from the analysis. The median follow-up was 77 months (range 17-110 months). Five-year overall survival (OS) and progression-free survival (PFS) were 91.7 and 79.2 %, respectively, which were higher than the equivalents in previous studies. The OS and PFS in the high-risk group were lower than those in the high-intermediate group. Treatment-related mortalities or fatal complication were not observed. Our results confirm that HDT/ASCT for high-risk aggressive lymphoma is a feasible and promising therapy, but patients with high IPI continued to have poor prognoses; improvements in treatment strategy are clearly needed. Since HDT/ASCT is an aggressive treatment option associated with long-term complications, we need to identify patient groups that will gain the maximum benefit from HDT/ASCT in the upfront setting.

  16. Clinicopathological features of histological transformation from extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue to diffuse large B-cell lymphoma: an analysis of 467 patients.

    Science.gov (United States)

    Maeshima, Akiko Miyagi; Taniguchi, Hirokazu; Toyoda, Kosuke; Yamauchi, Nobuhiko; Makita, Shinichi; Fukuhara, Suguru; Munakata, Wataru; Maruyama, Dai; Kobayashi, Yukio; Tobinai, Kensei

    2016-09-01

    This study analysed incidence, patient outcome, immunophenotype and prognostic factors of histological transformation (HT) from extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) to diffuse large B-cell lymphoma (DLBCL) in 467 patients (median age, 61 years). The primary sites of MALT lymphoma were the stomach (43%), ocular adnexa (25%), lung (8%), systemic (8%) and other tissues (16%). HT occurred in 8% of MALT lymphomas. Risk of HT by 15 years was 5%: 4% in limited-stage diseases (n = 385) and 16% in advanced-stage diseases (n = 56) (P = 0·02). The median time to HT was 48 months (range, 4-139). Five-year progression-free survival (PFS) and overall survival (OS) rates after HT were 80% and 94%, respectively. Immunohistochemical results of DLBCL were as follows: germinal centre B-cell (GCB)/non-GCB, 37%/63%; CD10, 9%; BCL6, 59%; MUM1, 38%; MYC, 42%; BCL2, 35%; Ki67 ≥ 90%, 23%; and CD5, 3%. The majority (75%, 9/12) of GCB-type DLBCLs exhibited CD10(-) , BCL6(+) and MUM1(-) immunophenotypes; the remainder had CD10(+) immunophenotypes. Multivariate analysis revealed that only advanced stage at HT was a significant adverse factor for PFS (P = 0·037). Thus, overall risk of HT was low and prognosis after HT was favourable; however, in advanced-stage cases, risk of HT was relatively high and prognosis was unfavourable. © 2016 John Wiley & Sons Ltd.

  17. CD3+/CD8+ T-cell density and tumoral PD-L1 predict survival irrespective of rituximab treatment in Chinese diffuse large B-cell lymphoma patients.

    Science.gov (United States)

    Shi, Yunfei; Deng, Lijuan; Song, Yuqin; Lin, Dongmei; Lai, Yumei; Zhou, LiXin; Yang, Lei; Li, Xianghong

    2018-05-10

    To investigate the prognostic value of tumor-infiltrating T-cell density and programmed cell death ligand-1 (PD-L1) expression in diffuse large B cell lymphoma (DLBCL). One-hundred-twenty-five Chinese DLBCL patients were enrolled in our study and provided samples; 76 of all cases were treated with rituximab (R). Tumor tissues were immunostained and analyzed for CD3+ and CD8+ tumor-infiltrating T-cell density, tumoral PD-L1, and microenvironmental PD-L1 (mPD-L1). The density of CD3 was rated as high in 33.6% cases, while 64.0% of DLBCLs were classified as high CD8 density. Of all cases, 16.8% were PD-L1+. Of the remaining PD-L1-DLBCLs, 29.8% positively expressed mPD-L1. Both CD3 high density and CD8 high density were associated with mPD-L1 positivity (P = 0.001 and P = 0.0001). In multivariate analysis, independently, high CD3 density predicted better OS (P = 0.023), while CD8 high density and PD-L1 positivity were both associated with prolonged PFS (P = 0.013 and P = 0.036, respectively). Even in the subgroup treated with R, univariate analyses indicated that high CD3 density and PD-L1 positivity were associated with better OS (P = 0.041) and PFS (P = 0.033), respectively. The infiltrating densities of CD3+ T-cells, CD8+ T-cells, and PD-L1 expression are predictive of survival in DLBCLs, irrespective of R usage.

  18. Diffusion archeology for diffusion progression history reconstruction.

    Science.gov (United States)

    Sefer, Emre; Kingsford, Carl

    2016-11-01

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

  19. Entropy as a measure of diffusion

    International Nuclear Information System (INIS)

    Aghamohammadi, Amir; Fatollahi, Amir H.; Khorrami, Mohammad; Shariati, Ahmad

    2013-01-01

    The time variation of entropy, as an alternative to the variance, is proposed as a measure of the diffusion rate. It is shown that for linear and time-translationally invariant systems having a large-time limit for the density, at large times the entropy tends exponentially to a constant. For systems with no stationary density, at large times the entropy is logarithmic with a coefficient specifying the speed of the diffusion. As an example, the large-time behaviors of the entropy and the variance are compared for various types of fractional-derivative diffusions.

  20. Entropy as a measure of diffusion

    Energy Technology Data Exchange (ETDEWEB)

    Aghamohammadi, Amir, E-mail: mohamadi@alzahra.ac.ir; Fatollahi, Amir H., E-mail: fath@alzahra.ac.ir; Khorrami, Mohammad, E-mail: mamwad@mailaps.org; Shariati, Ahmad, E-mail: shariati@mailaps.org

    2013-10-15

    The time variation of entropy, as an alternative to the variance, is proposed as a measure of the diffusion rate. It is shown that for linear and time-translationally invariant systems having a large-time limit for the density, at large times the entropy tends exponentially to a constant. For systems with no stationary density, at large times the entropy is logarithmic with a coefficient specifying the speed of the diffusion. As an example, the large-time behaviors of the entropy and the variance are compared for various types of fractional-derivative diffusions.

  1. Computational Diffusion MRI : MICCAI Workshop

    CERN Document Server

    Grussu, Francesco; Ning, Lipeng; Tax, Chantal; Veraart, Jelle

    2018-01-01

    This volume presents the latest developments in the highly active and rapidly growing field of diffusion MRI. The reader will find numerous contributions covering a broad range of topics, from the mathematical foundations of the diffusion process and signal generation, to new computational methods and estimation techniques for the in-vivo recovery of microstructural and connectivity features, as well as frontline applications in neuroscience research and clinical practice. These proceedings contain the papers presented at the 2017 MICCAI Workshop on Computational Diffusion MRI (CDMRI’17) held in Québec, Canada on September 10, 2017, sharing new perspectives on the most recent research challenges for those currently working in the field, but also offering a valuable starting point for anyone interested in learning computational techniques in diffusion MRI. This book includes rigorous mathematical derivations, a large number of rich, full-colour visualisations and clinically relevant results. As such, it wil...

  2. Excess Entropy and Diffusivity

    Indian Academy of Sciences (India)

    First page Back Continue Last page Graphics. Excess Entropy and Diffusivity. Excess entropy scaling of diffusivity (Rosenfeld,1977). Analogous relationships also exist for viscosity and thermal conductivity.

  3. Intra-patient variability of FDG standardized uptake values in mediastinal blood pool, liver, and myocardium during R-CHOP chemotherapy in patients with diffuse large B- cell lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Soo Jeong; Yi, Hyun Kyung; Lim, Chae Hong; Cho, Young Seok; Choi, Joon Young; Choe, Yeam Seong; Lee, Kyung Han; Moon, Seung Hwan [Dept. of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2016-12-15

    {sup 18}F-fluorodeoxyglucose (FDG) PET/CT is useful for staging and evaluating treatment response in patients with diffuse large B-cell lymphoma (DLBCL). A five-point scale model using the mediastinal blood pool (MBP) and liver as references is a recommended method for interpreting treatment response. We evaluated the variability in standardized uptake values (SUVs) of the MBP, liver, and myocardium during chemotherapy in patients with DLBCL. We analyzed 60 patients with DLBCL who received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) treatment and underwent baseline, interim, and final FDG PET/CT scans. The FDG uptakes of lymphoma lesions, MBP, liver, and myocardium were assessed, and changes in the MBP and liver SUV and possible associated factors were evaluated. The SUV of the liver did not change significantly during the chemotherapy. However, the SUV{sub mean} of MBP showed a significant change though the difference was small (p = 0.019). SUV{sub mean} of MBP and liver at baseline and interim scans was significantly lower in patients with advanced Ann Arbor stage on diagnosis. The SUV{sub mean} of the MBP and liver was negatively correlated with the volumetric index of lymphoma lesions in baseline scans (r = -0.547, p < 0.001; r = -0.502, p < 0.001). Positive myocardial FDG uptake was more frequently observed in interim and final scans than in the baseline scan, but there was no significant association between the MBP and liver uptake and myocardial uptake. The SUV of the liver was not significantly changed during R-CHOP chemotherapy in patients with DLBCL, whereas the MBP SUV of the interim scan decreased slightly. However, the SUV of the reference organs may be affected by tumor burden, and this should be considered when assessing follow-up scans. Although myocardial FDG uptake was more frequently observed after R-CHOP chemotherapy, it did not affect the SUV of the MBP and liver.

  4. Phase III Randomized Study of Rituximab/Carmustine, Etoposide, Cytarabine, and Melphalan (BEAM) Compared With Iodine-131 Tositumomab/BEAM With Autologous Hematopoietic Cell Transplantation for Relapsed Diffuse Large B-Cell Lymphoma: Results From the BMT CTN 0401 Trial

    Science.gov (United States)

    Vose, Julie M.; Carter, Shelly; Burns, Linda J.; Ayala, Ernesto; Press, Oliver W.; Moskowitz, Craig H.; Stadtmauer, Edward A.; Mineshi, Shin; Ambinder, Richard; Fenske, Timothy; Horowitz, Mary; Fisher, Richard; Tomblyn, Marcie

    2013-01-01

    Purpose This clinical trial evaluated standard-dose radioimmunotherapy with a chemotherapy-based transplantation regimen followed by autologous hematopoietic cell transplantation versus rituximab with the same regimen in patients with relapsed diffuse large B-cell lymphoma (DLBCL). Patients and Methods Patients with chemotherapy-sensitive persistent or relapsed DLBCL were randomly assigned to receive iodine-131 tositumomab (dosimetric dose of 5 mCi on day −19 and therapeutic dose of 0.75 Gy on day −12), carmustine 300 mg/m2 (day −6), etoposide 100 mg/m2 twice daily (days −5 to −2), cytarabine 100 mg/m2 twice daily (days −5 to −2), and melphalan 140 mg/m2 (day −1; B-BEAM) or rituximab 375 mg/m2 on days −19 and −12 and the same chemotherapy regimen (R-BEAM). Results Two hundred twenty-four patients were enrolled, with 113 patients randomly assigned to R-BEAM and 111 patients assigned to B-BEAM. Two-year progression-free survival (PFS) rates, the primary end point, were 48.6% (95% CI, 38.6% to 57.8%) for R-BEAM and 47.9% (95% CI, 38.2% to 57%; P = .94) for B-BEAM, and the 2-year overall survival (OS) rates were 65.6% (95% CI, 55.3% to 74.1%) for R-BEAM and 61% (95% CI, 50.9% to 69.9%; P = .38) for B-BEAM. The 100-day treatment-related mortality rates were 4.1% (95% CI, 0.2% to 8.0%) for R-BEAM and 4.9% (95% CI, 0.8% to 9.0%; P = .97) for B-BEAM. The maximum mucositis score was higher in the B-BEAM arm (0.72) compared with the R-BEAM arm (0.31; P < .001). Conclusion The B-BEAM and R-BEAM regimens produced similar 2-year PFS and OS rates for patients with chemotherapy-sensitive relapsed DLBCL. No differences in toxicities other than mucositis were noted. PMID:23478060

  5. Randomized Phase II Study of R-CHOP With or Without Bortezomib in Previously Untreated Patients With Non-Germinal Center B-Cell-Like Diffuse Large B-Cell Lymphoma.

    Science.gov (United States)

    Leonard, John P; Kolibaba, Kathryn S; Reeves, James A; Tulpule, Anil; Flinn, Ian W; Kolevska, Tatjana; Robles, Robert; Flowers, Christopher R; Collins, Robert; DiBella, Nicholas J; Papish, Steven W; Venugopal, Parameswaran; Horodner, Andrew; Tabatabai, Amir; Hajdenberg, Julio; Park, Jaehong; Neuwirth, Rachel; Mulligan, George; Suryanarayan, Kaveri; Esseltine, Dixie-Lee; de Vos, Sven

    2017-11-01

    Purpose To evaluate the impact of the addition of bortezomib to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) on outcomes in previously untreated patients with non-germinal center B-cell-like (non-GCB) diffuse large B-cell lymphoma (DLBCL). Patients and Methods After real-time determination of non-GCB DLBCL using the Hans immunohistochemistry algorithm, 206 patients were randomly assigned (1:1; stratified by International Prognostic Index [IPI] score) to six 21-day cycles of standard R-CHOP alone or R-CHOP plus bortezomib 1.3 mg/m 2 intravenously on days 1 and 4 (VR-CHOP). The primary end point, progression-free survival (PFS), was evaluated in 183 patients with centrally confirmed non-GCB DLBCL who received one or more doses of study drug (91 R-CHOP, 92 VR-CHOP). Results After a median follow-up of 34 months, with 25% (R-CHOP) and 18% (VR-CHOP) of patients having had PFS events, the hazard ratio (HR) for PFS was 0.73 (90% CI, 0.43 to 1.24) with VR-CHOP ( P = .611). Two-year PFS rates were 77.6% with R-CHOP and 82.0% with VR-CHOP; they were 65.1% versus 72.4% in patients with high-intermediate/high IPI (HR, 0.67; 90% CI, 0.34 to 1.29), and 90.0% versus 88.9% (HR, 0.85; 90% CI, 0.35 to 2.10) in patients with low/low-intermediate IPI. Overall response rate with R-CHOP and VR-CHOP was 98% and 96%, respectively. The overall survival HR was 0.75 (90% CI, 0.38 to 1.45); 2-year survival rates were 88.4% and 93.0%, respectively. In the safety population (100 R-CHOP and 101 VR-CHOP patients), grade ≥ 3 adverse events included neutropenia (53% v 49%), thrombocytopenia (13% v 29%), anemia (7% v 15%), leukopenia (26% v 25%), and neuropathy (1% v 5%). Conclusion Outcomes for newly diagnosed, prospectively enrolled patients with non-GCB DLBCL were more favorable than expected with R-CHOP and were not significantly improved by adding bortezomib.

  6. Higher-order tensors in diffusion imaging

    NARCIS (Netherlands)

    Schultz, T.; Fuster, A.; Ghosh, A.; Deriche, R.; Florack, L.M.J.; Lim, L.H.; Westin, C.-F.; Vilanova, A.; Burgeth, B.

    2014-01-01

    Diffusion imaging is a noninvasive tool for probing the microstructure of fibrous nerve and muscle tissue. Higher-order tensors provide a powerful mathematical language to model and analyze the large and complex data that is generated by its modern variants such as High Angular Resolution Diffusion

  7. Derivation of the neutron diffusion equation

    International Nuclear Information System (INIS)

    Mika, J.R.; Banasiak, J.

    1994-01-01

    We discuss the diffusion equation as an asymptotic limit of the neutron transport equation for large scattering cross sections. We show that the classical asymptotic expansion procedure does not lead to the diffusion equation and present two modified approaches to overcome this difficulty. The effect of the initial layer is also discussed. (authors). 9 refs

  8. Diffusing diffusivity: Rotational diffusion in two and three dimensions

    Science.gov (United States)

    Jain, Rohit; Sebastian, K. L.

    2017-06-01

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

  9. Diffusion in solids

    International Nuclear Information System (INIS)

    Tiwari, G.P.; Kale, G.B.; Patil, R.V.

    1999-01-01

    The article presents a brief survey of process of diffusion in solids. It is emphasised that the essence of diffusion is the mass transfer through the atomic jumps. To begin with formal equations for diffusion coefficient are presented. This is followed by discussions on mechanisms of diffusion. Except for solutes which form interstitial solid solution, diffusion in majority of cases is mediated through exchange of sites between an atom and its neighbouring vacancy. Various vacancy parameters such as activation volume, correlation factor, mass effect etc are discussed and their role in establishing the mode of diffusion is delineated. The contribution of dislocations and grain boundaries in diffusion process is brought out. The experimental determination of different types of diffusion coefficients are described. Finally, the pervasive nature of diffusion process in number of commercial processes is outlined to show the importance of diffusion studies in materials science and technology. (author)

  10. Liver imaging at 3.0 T: Diffusion-induced black-blood echo-planar imaging with large anatomic volumetric coverage as an alternative for specific absorption rate-intensive echo-train spin-echo sequences: Feasibility study

    NARCIS (Netherlands)

    I.C. van den Bos (Indra); S.M. Hussain (Shahid); G.P. Krestin (Gabriel); P.A. Wielopolski (Piotr)

    2008-01-01

    textabstractInstitutional Review Board approval and signed informed consent were obtained by all participants for an ongoing sequence optimization project at 3.0 T. The purpose of this study was to evaluate breath-hold diffusion-induced blackblood echo-planar imaging (BBEPI) as a potential

  11. Diffusion archeology for diffusion progression history reconstruction

    OpenAIRE

    Sefer, Emre; Kingsford, Carl

    2015-01-01

    Diffusion through graphs can be used to model many real-world processes, such as the spread of diseases, social network memes, computer viruses, or water contaminants. Often, a real-world diffusion cannot be directly observed while it is occurring — perhaps it is not noticed until some time has passed, continuous monitoring is too costly, or privacy concerns limit data access. This leads to the need to reconstruct how the present state of the diffusion came to be from partial d...

  12. Diffusion in condensed matter methods, materials, models

    CERN Document Server

    Kärger, Jörg

    2005-01-01

    Diffusion as the process of particle transport due to stochastic movement is a phenomenon of crucial relevance for a large variety of processes and materials. This comprehensive, handbook- style survey of diffusion in condensed matter gives detailed insight into diffusion as the process of particle transport due to stochastic movement. Leading experts in the field describe in 23 chapters the different aspects of diffusion, covering microscopic and macroscopic experimental techniques and exemplary results for various classes of solids, liquids and interfaces as well as several theoretical concepts and models. Students and scientists in physics, chemistry, materials science, and biology will benefit from this detailed compilation.

  13. [Survival of patients with primary central nervous system diffuse large B-cell lymphoma: impact of gene aberrations and protein overexpression of bcl-2 and C-MYC, and selection of chemotherapy regimens].

    Science.gov (United States)

    Yin, W J; Zhu, X; Yang, H Y; Sun, W Y; Wu, M J

    2018-01-08

    Objective: To investigate the impact of clinicopathological features, gene rearrangements and protein expression of bcl-6, bcl-2, C-MYC and chemotherapy regime on the prognosis of patients with primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL). Methods: Thirty-three cases of PCNS-DLBCL diagnosed from January 2006 to December 2016 at Zhejiang Cancer Hospital were collected. The expression of CD10, bcl-6, bcl-2, MUM1 and MYC were detected by immunohistochemical staining (IHC). The presence of EB virus was detected by in situ hybridization(EBER). Copy number variation (ICN) and translocation status of bcl-6, bcl-2 and C-MYC genes were detected by fluorescence in situ hybridization (FISH). The relationship between the above indexes and the prognosis was analyzed by univariate, bivariate survival analysis and multiple Cox hazard regression analysis. Results: The study included 33 patients of PCNS-DLBCL, without evidence of primary or secondary immunodeficient disease. Male to female ratio was 1.36∶1.00, and the average age was 56 years. Twenty cases had single lesion while 13 had multiple lesions. Deep brain involvement was seen in 12 cases. All patients underwent partial or total tumor resection. Five patients received whole brain post-surgery radiotherapy, nine patients received high-dose methotrexate (HD-MTX) based chemotherapy, and 12 patients received whole-brain radiotherapy combined with HD-MTX based chemotherapy. Severn patients received no further treatment and rituximab was used in 8 patients. According to the Hans model, 27 cases were classified as non-GCB subtypes (81.8%). Bcl-2 was positive in 25 cases (75.8%, 25/33) and highly expressed in 8 (24.2%). MYC was positive in 12 cases (36.4%) and double expression of bcl-2 and MYC was seen in 6 cases. EBER positive rate was 10.0%(3/30), all of which had multiple lesions. Two bcl-6 gene translocations and 3 amplifications were found in 28 patients. Two translocations, 3 ICN or with both

  14. Mechanisms of impurity diffusion in rutile

    International Nuclear Information System (INIS)

    Peterson, N.L.; Sasaki, J.

    1984-01-01

    Tracer diffusion of 46 Sc, 51 Cr, 54 Mn, 59 Fe, 60 Co, 63 Ni, and 95 Zr, was measured as functions of crystal orientation, temperature, and oxygen partial pressure in rutile single crystals using the radioactive tracer sectioning technique. Compared to cation self-diffusion, divalent impurities (e.g., Co and Ni) diffuse extremely rapidly in TiO 2 and exhibit a large anisotropy in the diffusion behavior; divalent-impurity diffusion parallel to the c-axis is much larger than it is perpendicular to the c-axis. The diffusion of trivalent impurity ions (Sc and Cr) and tetravalent impurity ions (Zr) is similar to cation self-diffusion, as a function of temperature and of oxygen partial pressure. The divalent impurity ions Co and Ni apparently diffuse as interstitial ions along open channels parallel to the c-axis. The results suggest that Sc, Cr, and Zr ions diffuse by an interstitialcy mechanism involving the simultaneous and cooperative migration of tetravalent interstitial titanium ions and the tracer-impurity ions. Iron ions diffused both as divalent and as trivalent ions. 8 figures

  15. Advection endash diffusion around a curved obstacle

    International Nuclear Information System (INIS)

    Ahluwalia, D.S.; Keller, J.B.; Knessl, C.

    1998-01-01

    Advection and diffusion of a substance around a curved obstacle is analyzed when the advection velocity is large compared to the diffusion velocity, i.e., when the Peclet number is large. Asymptotic expressions for the concentration are obtained by the use of boundary layer theory, matched asymptotic expansions, etc. The results supplement and extend previous ones for straight obstacles. They apply to electrophoresis, the flow of ground water, chromatography, sedimentation, etc. copyright 1998 American Institute of Physics

  16. Spin-diffusions and diffusive molecular dynamics

    Science.gov (United States)

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

    2017-12-01

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

  17. Gaseous diffusion -- the enrichment workhorse

    International Nuclear Information System (INIS)

    Shoemaker, J.E. Jr.

    1984-01-01

    Construction of the first large-scale gaseous diffusion facility was started as part of the Manhattan Project in Oak Ridge, Tennessee, in 1943. This facility, code named ''K-25,'' began operation in January 1945 and was fully on stream by September 1945. Four additional process buildings were later added in Oak Ridge as the demand for enriched uranium escalated. New gaseous diffusion plants were constructed at Paducah, Kentucky, and Portsmouth, Ohio, during this period. The three gaseous diffusion plants were the ''workhorses'' which provided the entire enriched uranium demand for the United States during the 1950s and 1960s. As the demand for enriched uranium for military purposes decreased during the early 1960s, power to the diffusion plants was curtailed to reduce production. During the 1960s, as plans for the nuclear power industry were formulated, the role of the diffusion plants gradually changed from providing highly-enriched uranium for the military to providing low-enriched uranium for power reactors

  18. Diffusion in reactor materials

    International Nuclear Information System (INIS)

    Fedorov, G.B.; Smirnov, E.A.

    1984-01-01

    The monograph contains a brief description of the principles underlying the theory of diffusion, as well as modern methods of studying diffusion. Data on self-diffusion and diffusion of impurities in a nuclear fuel and fissionable materials (uranium, plutonium, thorium, zirconium, titanium, hafnium, niobium, molybdenum, tungsten, beryllium, etc.) is presented. Anomalous diffusion, diffusion of components, and interdiffusion in binary and ternary alloys were examined. The monograph presents the most recent reference material on diffusion. It is intended for a wide range of researchers working in the field of diffusion in metals and alloys and attempting to discover new materials for application in nuclear engineering. It will also be useful for teachers, research scholars and students of physical metallurgy

  19. Diffusion in flowing gas

    International Nuclear Information System (INIS)

    Reus, K.W.

    1979-01-01

    This thesis is concerned with the back-diffusion method of calculating the mutual diffusion coefficient of two gases. The applicability of this method for measuring diffusion coefficients at temperatures up to 1300 K is considered. A further aim of the work was to make a contribution to the description of the interatomic potential energy of noble gases at higher energies as a function of the internuclear distance. This was achieved with the measured diffusion coefficients, especially with those for high temperatures. (Auth.)

  20. Diffusion Under Geometrical Constraint

    OpenAIRE

    Ogawa, Naohisa

    2014-01-01

    Here we discus the diffusion of particles in a curved tube. This kind of transport phenomenon is observed in biological cells and porous media. To solve such a problem, we discuss the three dimensional diffusion equation with a confining wall forming a thinner tube. We find that the curvature appears in a effective diffusion coefficient for such a quasi-one-dimensional system. As an application to higher dimensional case, we discuss the diffusion in a curved surface with ...

  1. Diffuse ceiling ventilation

    DEFF Research Database (Denmark)

    Zhang, Chen

    Diffuse ceiling ventilation is an innovative ventilation concept where the suspended ceiling serves as air diffuser to supply fresh air into the room. Compared with conventional ventilation systems, diffuse ceiling ventilation can significantly reduce or even eliminate draught risk due to the low...

  2. Diffusion and particle mobility in 1D system

    International Nuclear Information System (INIS)

    Borman, V.D.; Johansson, B.; Skorodumova, N.V.; Tronin, I.V.; Tronin, V.N.; Troyan, V.I.

    2006-01-01

    The transport properties of one-dimensional (1D) systems have been studied theoretically. Contradictory experimental results on molecular transport in quasi-1D systems, such as zeolite structures, when both diffusion transport acceleration and the existence of the diffusion mode with lower particle mobility (single-file diffusion ( 2 >∼t 1/2 )) have been reported, are consolidated in a consistent model. Transition from the single-file diffusion mode to an Einstein-like diffusion 2 >∼t with diffusion coefficient increasing with the density has been predicted to occur at large observation times

  3. Diffusion mechanisms in grain boundaries in solids

    International Nuclear Information System (INIS)

    Peterson, N.L.

    1982-01-01

    A critical review is given of our current knowledge of grain-boundary diffusion in solids. A pipe mechanism of diffusion based on the well-established dislocation model seems most appropriate for small-angle boundaries. Open channels, which have atomic configurations somewhat like dislocation cores, probably play a major role in large-angle grain-boundary diffusion. Dissociated dislocations and stacking faults are not efficient paths for grain-boundary diffusion. The diffusion and computer modeling experiments are consistent with a vacancy mechanism of diffusion by a rather well-localized vacancy. The effective width of a boundary for grain-boundary diffusion is about two atomic planes. These general features of grain-boundary diffusion, deduced primarily from experiments on metals, are thought to be equally applicable for pure ceramic solids. The ionic character of many ceramic oxides may cause some differences in grain-boundary structure from that observed in metals, resulting in changes in grain-boundary diffusion behavior. 72 references, 5 figures

  4. Thermal diffusion (1963); Diffusion thermique (1963)

    Energy Technology Data Exchange (ETDEWEB)

    Lemarechal, A [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1963-07-01

    This report brings together the essential principles of thermal diffusion in the liquid and gaseous phases. The macroscopic and molecular aspects of the thermal diffusion constant are reviewed, as well as the various measurement method; the most important developments however concern the operation of the CLUSIUS and DICKEL thermo-gravitational column and its applications. (author) [French] Ce rapport rassemble les principes essentiels de la diffusion thermique en phase liquide et en phase gazeuse. Les aspects macroscopique et moleculaire de la constante de diffusion thermique sont passes en revue ainsi que ses differentes methodes de mesure; mais les developpements les plus importants concernent le fonctionnement de ls colonne thermogravitationnelle de CLUSIUS et DICKEL et ses applications. (auteur)

  5. Transport phenomena in sharply contrasting media with a diffusion barrier

    International Nuclear Information System (INIS)

    Dvoretskaya, O A; Kondratenko, P S

    2011-01-01

    Using the advection–diffusion equation, we analytically study contaminant transport in a sharply contrasting medium with a diffusion barrier due to localization of a contaminant source in a low-permeability medium. Anomalous diffusion behavior and a crossover between different transport regimes are observed. The diffusion barrier results in exponential attenuation of the source power, retardation of the contaminant plume growth and modification of the concentration distribution at large distances. (paper)

  6. Stability of Gradient Field Corrections for Quantitative Diffusion MRI

    OpenAIRE

    Rogers, Baxter P.; Blaber, Justin; Welch, E. Brian; Ding, Zhaohua; Anderson, Adam W.; Landman, Bennett A.

    2017-01-01

    In magnetic resonance diffusion imaging, gradient nonlinearity causes significant bias in the estimation of quantitative diffusion parameters such as diffusivity, anisotropy, and diffusion direction in areas away from the magnet isocenter. This bias can be substantially reduced if the scanner- and coil-specific gradient field nonlinearities are known. Using a set of field map calibration scans on a large (29 cm diameter) phantom combined with a solid harmonic approximation of the gradient fie...

  7. Study of ODE limit problems for reaction-diffusion equations

    Directory of Open Access Journals (Sweden)

    Jacson Simsen

    2018-01-01

    Full Text Available In this work we study ODE limit problems for reaction-diffusion equations for large diffusion and we study the sensitivity of nonlinear ODEs with respect to initial conditions and exponent parameters. Moreover, we prove continuity of the flow and weak upper semicontinuity of a family of global attractors for reaction-diffusion equations with spatially variable exponents when the exponents go to 2 in \\(L^{\\infty}(\\Omega\\ and the diffusion coefficients go to infinity.

  8. Diffusion bonding in compact heat exchangers

    International Nuclear Information System (INIS)

    Southall, David

    2009-01-01

    Heatric's diffusion bonding process is a solid-state joining technology that produces strong, compact, all-metal heat exchanger cores. Diffusion bonding allows for a large quantity of joints to be made in geometries that would normally be inaccessible for conventional welding techniques. Since Heatric's diffusion bonding process uses no interlayer or braze alloy, the resulting heat exchanger core has consistent chemistry throughout and, under carefully controlled conditions, a return to parent metal strength can be reached. This paper will provide an overview of the diffusion bonding process and its origins, and also its application to compact heat exchanger construction. The paper will then discuss recent work that has been done to compare mechanical properties of Heatric's diffusion bonded material with material that has been conventionally welded, as well as with material tested in the as-received condition. (author)

  9. Unexpected consequences of bedload diffusion

    Science.gov (United States)

    Devauchelle, O.; Abramian, A.; Lajeunesse, E.

    2017-12-01

    Sedimentary grains transported as bedload bump and bounce on the rough bed of the river that entrains them. The succession of these random events causes bedload particles to diffuse across the flow, towards the less active areas of the bed. In a fashion reminiscent of that proposed by Parker (1978) for suspended load, this mechanism opposes gravity to maintain the banks of alluvial rivers. In fact, diffusion is so tightly linked to bedload that it appears in the most basic sediment transport experiment--the straight channel we use to calibrate transport laws. Indeed, the fixed sides of the channel cause the flow, and thus the bed shear stress, to vary across the flume. This variation induces bedload diffusion, which in turn deforms the bed. As a consequence, to reliably calibrate a transport law, we need to measure the full profiles of shear stress and bedload transport, rather than bulk-average these quantities. Unfortunately, using a larger channel does not solve the problem, as a large aspect ratio favors the growth of streaks caused by a diffusion-induced instability. Based on these observations, we propose a different design for sediment transport experiments.

  10. Metric diffusion along foliations

    CERN Document Server

    Walczak, Szymon M

    2017-01-01

    Up-to-date research in metric diffusion along compact foliations is presented in this book. Beginning with fundamentals from the optimal transportation theory and the theory of foliations; this book moves on to cover Wasserstein distance, Kantorovich Duality Theorem, and the metrization of the weak topology by the Wasserstein distance. Metric diffusion is defined, the topology of the metric space is studied and the limits of diffused metrics along compact foliations are discussed. Essentials on foliations, holonomy, heat diffusion, and compact foliations are detailed and vital technical lemmas are proved to aide understanding. Graduate students and researchers in geometry, topology and dynamics of foliations and laminations will find this supplement useful as it presents facts about the metric diffusion along non-compact foliation and provides a full description of the limit for metrics diffused along foliation with at least one compact leaf on the two dimensions.

  11. Finite-difference schemes for anisotropic diffusion

    Energy Technology Data Exchange (ETDEWEB)

    Es, Bram van, E-mail: es@cwi.nl [Centrum Wiskunde and Informatica, P.O. Box 94079, 1090GB Amsterdam (Netherlands); FOM Institute DIFFER, Dutch Institute for Fundamental Energy Research, Association EURATOM-FOM (Netherlands); Koren, Barry [Eindhoven University of Technology (Netherlands); Blank, Hugo J. de [FOM Institute DIFFER, Dutch Institute for Fundamental Energy Research, Association EURATOM-FOM (Netherlands)

    2014-09-01

    In fusion plasmas diffusion tensors are extremely anisotropic due to the high temperature and large magnetic field strength. This causes diffusion, heat conduction, and viscous momentum loss, to effectively be aligned with the magnetic field lines. This alignment leads to different values for the respective diffusive coefficients in the magnetic field direction and in the perpendicular direction, to the extent that heat diffusion coefficients can be up to 10{sup 12} times larger in the parallel direction than in the perpendicular direction. This anisotropy puts stringent requirements on the numerical methods used to approximate the MHD-equations since any misalignment of the grid may cause the perpendicular diffusion to be polluted by the numerical error in approximating the parallel diffusion. Currently the common approach is to apply magnetic field-aligned coordinates, an approach that automatically takes care of the directionality of the diffusive coefficients. This approach runs into problems at x-points and at points where there is magnetic re-connection, since this causes local non-alignment. It is therefore useful to consider numerical schemes that are tolerant to the misalignment of the grid with the magnetic field lines, both to improve existing methods and to help open the possibility of applying regular non-aligned grids. To investigate this, in this paper several discretization schemes are developed and applied to the anisotropic heat diffusion equation on a non-aligned grid.

  12. Diffusion of improved biomass stoves in China

    International Nuclear Information System (INIS)

    Daxiong Qiu; Shuhua Gu; Catania, P.; Kun Huang

    1996-01-01

    The large-scale utilization of inefficient biofuel stoves for cooking and heating in the rural areas of China can cause ecological and environmental problems; thus, in 1982, the Chinese government encouraged the diffusion of improved biomass stoves. From 1982 to 1994, these improved biomass stoves have been used by 144 million households or the equivalent of 90% of all improved stoves installed globally; 62% of the Chinese market has been penetrated. This paper presents the fundamental features of China's diffusion programme of improved biomass stoves, analyses of the future domestic market, and defines some of the lessons learned from the diffusion programme which may be applicable in other emerging nations. (Author)

  13. Diffusion of tritiated water in coastal areas

    International Nuclear Information System (INIS)

    Fukuda, M.; Kasai, A.; Imai, T.; Amano, H.; Yanase, N.

    1980-01-01

    The diffusion of tritiated water discharged by Japan Atomic Energy Research Institute at shore line has been investigated. In continuous discharge, the concentration of tritiated water in samples taken at a point downstream fluctuates largely. To reveal the cause, dye diffusion experiments were made in the coastal area. The shapes of dye cloud were photographed by a remote-control camera suspended from a captive balloon as color pictures. The movement of dye is so complex that a three-dimensional model must be employed to assess the diffusion in coastal areas

  14. A3 Subscale Diffuser Test Article Design

    Science.gov (United States)

    Saunders, G. P.

    2009-01-01

    This paper gives a detailed description of the design of the A3 Subscale Diffuser Test (SDT) Article Design. The subscale diffuser is a geometrically accurate scale model of the A3 altitude rocket facility. It was designed and built to support the SDT risk mitigation project located at the E3 facility at Stennis Space Center, MS (SSC) supporting the design and construction of the A3 facility at SSC. The subscale test article is outfitted with a large array of instrumentation to support the design verification of the A3 facility. The mechanical design of the subscale diffuser and test instrumentation are described here

  15. Magnetic diffuse scattering: a theorist's perspective

    International Nuclear Information System (INIS)

    Long, M.W.

    1996-01-01

    We attempt to show that magnetic diffuse scattering is the natural probe for frustrated antiferromagnetism. Comparison between nuclear and magnetic diffuse scattering compares the range of atomic clustering with the range of the magnetic impurity. At low temperature frustration is expected to lead to large differences which are a natural signature for the relevance of such frustration effects. We provide some elementary examples in first-row transition metals which display fairly dramatic effects. (author) 11 figs., tabs., 8 refs

  16. Benchmarks with diffusion theory and transport theory

    International Nuclear Information System (INIS)

    Cunha Menezes Filho, A. da; Souza, A.L. de.

    1984-01-01

    The multiplication factor and some spectral indices for five critical assemblies (ZPR-6-7, ZPR-3-11, GODIVA, BIG-TEN and FLATTOP) are calculated by Diffusion and Transport Theory, with group constants generated by MC 2 (for diffusion calculations) and by NJOY (for transport calculations). The discrepancies encountered in the ZPR-6-7 spectra, can be tracked to the large differences in the elastic cross section for Iron, calculated by MC 2 and NJOY. (Author) [pt

  17. Correlated diffusion imaging

    International Nuclear Information System (INIS)

    Wong, Alexander; Glaister, Jeffrey; Cameron, Andrew; Haider, Masoom

    2013-01-01

    Prostate cancer is one of the leading causes of cancer death in the male population. Fortunately, the prognosis is excellent if detected at an early stage. Hence, the detection and localization of prostate cancer is crucial for diagnosis, as well as treatment via targeted focal therapy. New imaging techniques can potentially be invaluable tools for improving prostate cancer detection and localization. In this study, we introduce a new form of diffusion magnetic resonance imaging called correlated diffusion imaging, where the tissue being imaged is characterized by the joint correlation of diffusion signal attenuation across multiple gradient pulse strengths and timings. By taking into account signal attenuation at different water diffusion motion sensitivities, correlated diffusion imaging can provide improved delineation between cancerous tissue and healthy tissue when compared to existing diffusion imaging modalities. Quantitative evaluation using receiver operating characteristic (ROC) curve analysis, tissue class separability analysis, and visual assessment by an expert radiologist were performed to study correlated diffusion imaging for the task of prostate cancer diagnosis. These results are compared with that obtained using T2-weighted imaging and standard diffusion imaging (via the apparent diffusion coefficient (ADC)). Experimental results suggest that correlated diffusion imaging provide improved delineation between healthy and cancerous tissue and may have potential as a diagnostic tool for cancer detection and localization in the prostate gland. A new form of diffusion magnetic resonance imaging called correlated diffusion imaging (CDI) was developed for the purpose of aiding radiologists in cancer detection and localization in the prostate gland. Preliminary results show CDI shows considerable promise as a diagnostic aid for radiologists in the detection and localization of prostate cancer

  18. Gaseous diffusion system

    International Nuclear Information System (INIS)

    Garrett, G.A.; Shacter, J.

    1978-01-01

    A gaseous diffusion system is described comprising a plurality of diffusers connected in cascade to form a series of stages, each of the diffusers having a porous partition dividing it into a high pressure chamber and a low pressure chamber, and means for combining a portion of the enriched gas from a succeeding stage with a portion of the enriched gas from the low pressure chamber of each stage and feeding it into one extremity of the high pressure chamber thereof

  19. Inpainting using airy diffusion

    Science.gov (United States)

    Lorduy Hernandez, Sara

    2015-09-01

    One inpainting procedure based on Airy diffusion is proposed, implemented via Maple and applied to some digital images. Airy diffusion is a partial differential equation with spatial derivatives of third order in contrast with the usual diffusion with spatial derivatives of second order. Airy diffusion generates the Airy semigroup in terms of the Airy functions which can be rewritten in terms of Bessel functions. The Airy diffusion can be used to smooth an image with the corresponding noise elimination via convolution. Also the Airy diffusion can be used to erase objects from an image. We build an algorithm using the Maple package ImageTools and such algorithm is tested using some images. Our results using Airy diffusion are compared with the similar results using standard diffusion. We observe that Airy diffusion generates powerful filters for image processing which could be incorporated in the usual packages for image processing such as ImageJ and Photoshop. Also is interesting to consider the possibility to incorporate the Airy filters as applications for smartphones and smart-glasses.

  20. Diffusion in compacted betonite

    International Nuclear Information System (INIS)

    Muurinen, A.; Rantanen, J.

    1985-01-01

    The objective of this report is to collect the literature bearing on the diffusion in compacted betonite, which has been suggested as possible buffer material for the disposal of spent fuel. Diffusion in a porous, water-saturated material is usually described as diffusion in the pore-water where sorption on the solid matter can delay the migration in the instationary state. There are also models which take into consideration that the sorbed molecules can also move while being sorbed. Diffusion experiments in compacted bentonite have been reported by many authors. Gases, anions, cations and actinides have been used as diffusing molecules. The report collects the results and the information on the measurement methods. On the basis of the results can be concluded that different particles possibly follow different diffusion mechanisms. The parameters which affect the diffusion seem to be for example the size, the electric charge and the sorption properties of the diffusing molecule. The report also suggest the parameters to be used in the diffusion calculation of the safety analyses of spent fuel disposal. (author)

  1. MR imaging evidence of anisotropic diffusion in the cat brain

    International Nuclear Information System (INIS)

    Moseley, M.E.; Mintorovich, J.; Cohen, Y.; Chilevitt, L.; Tsuruda, J.; Norman, D.; Weinstein, P.

    1989-01-01

    This paper discusses a study of diffusion behavior of brain water in the cat. Diffusion-weighted images, acquired with large gradient b values of 1,000-2,000 sec/mm 2 , showed no clear evidence of anisotropic water diffusion in either gray matter or basal ganglia. Large directional differences in image intensities and diffusion values were observed in cortical and deep white matter. Faster diffusion was sen when the direction of the applied diffusion gradient was parallel to the orientation of the white matter. Diffusion perpendicular to the gradient direction was significantly lower. This effect was proportional to gradient duration and strength and was seen in both pre- and immediate post-mortem images in all axial, sagittal, and coronal images

  2. Turbulent diffusion of small particles

    International Nuclear Information System (INIS)

    Margolin, L.G.

    1977-11-01

    The diffusion of small, spherical, rigid particles suspended in an incompressible turbulent fluid, but not interacting with each other, was studied. As a stochastic process, the turbulent fluid velocity field is assumed to be homogeneous, isotropic and stationary. Assuming the Stokes regime, a particle of equation of motion is used which includes only the effects of Stokes drag and a virtual mass force and an exact solution is found for the particle velocity correlation function, for all times and initial conditions, in terms of a fluid velocity correlation function measured along the motion of the particle. This shows that for times larger than a certain time scale, the particle velocity correlation becomes stationary. The effect of small shears in the fluid velocity was considered, under the additional restrictions of a certain high frequency regime for the turbulence. The shears convected past the particle much faster than the growth of the boundary layer. New force terms due to the presence of such shears are calculated and incorporated into the equation of motion. A perturbation solution to this equation is constructed, and the resultant particle velocity correlation function and diffusion coefficient are calculated. To lowest order, the particle diffusivity is found to be unaltered by the presence of small mean flow shears. The last model treated is one in which particles traverse a turbulent fluid with a large mean velocity. Among other restrictions, linearized form drag is assumed. The diffusion coefficient for such particles was calculated, and found to be much smaller than the passive scalar diffusion coefficient. This agrees within 5 percent with the experimental results of Snyder and Lumley

  3. Diffusion of oxygen in cork.

    Science.gov (United States)

    Lequin, Sonia; Chassagne, David; Karbowiak, Thomas; Simon, Jean-Marc; Paulin, Christian; Bellat, Jean-Pierre

    2012-04-04

    This work reports measurements of effective oxygen diffusion coefficient in raw cork. Kinetics of oxygen transfer through cork is studied at 298 K thanks to a homemade manometric device composed of two gas compartments separated by a cork wafer sample. The first compartment contains oxygen, whereas the second one is kept under dynamic vacuum. The pressure decrease in the first compartment is recorded as a function of time. The effective diffusion coefficient D(eff) is obtained by applying Fick's law to transient state using a numerical method based on finite differences. An analytical model derived from Fick's law applied to steady state is also proposed. Results given by these two methods are in close agreement with each other. The harmonic average of the effective diffusion coefficients obtained from the distribution of 15 cork wafers of 3 mm thickness is 1.1 × 10(-9) m(2) s(-1) with a large distribution over four decades. The statistical analysis of the Gaussian distribution obtained on a 3 mm cork wafer is extrapolated to a 48 mm cork wafer, which length corresponds to a full cork stopper. In this case, the probability density distribution gives a mean value of D(eff) equal to 1.6 × 10(-9) m(2) s(-1). This result shows that it is possible to obtain the effective diffusion coefficient of oxygen through cork from short time (few days) measurements performed on a thin cork wafer, whereas months are required to obtain the diffusion coefficient for a full cork stopper. Permeability and oxygen transfer rate are also calculated for comparison with data from other studies.

  4. Thermodynamics, diffusion and the Kirkendall effect in solids

    CERN Document Server

    Paul, Aloke; Vuorinen, Vesa; Divinski, Sergiy V

    2014-01-01

    Covering both basic and advanced thermodynamic and phase  principles,  as well as providing stability diagrams relevant for diffusion studies, Thermodynamics, Diffusion and the Kirkendall Effect in Solids maximizes reader insights into Fick’s laws of diffusion, atomic mechanisms, interdiffusion, intrinsic diffusion, tracer diffusion and the Kirkendall effect. Recent advances in the area of interdiffusion will be introduced, while the many practical examples and large number of illustrations given will serve to aid researches working in this area in learning the practical evaluation of various diffusion parameters from experimental results. With a unique approach to the two main focal points in solid state transformations, energetics (thermodynamics) and kinetics (interdiffusion) are extensively studied and their combined use in practise is discussed. Recent developments in the area of Kirkendall effect, grain boundary diffusion and multicomponent diffusion are also covered extensively. This book will appe...

  5. Étude des matrices sol-gel en film mince par détection de molécule unique en champ large : diffusion moléculaire et agrégation photo-induite

    Science.gov (United States)

    Nutarelli, D.; Débarre, A.; Jaffiol, R.; Julien, C.; Richard, A.; Tchénio, P.; Chaput, F.; Boilot, J. P.

    2004-11-01

    La fluorescence de molécules de colorant dans des matrices sol-gel en film mince a été étudiée par détection de molécule unique. Outre les phénomènes de photo-blanchiment et de clignotement, un processus de photo-agrégation a été observé. Ce phénomène, dont la dynamique dépend de la présence d'oxygène, de l'intensité du laser d'excitation et de la température, montre l'existence de deux classes de molécules dans l'échantillon. Des molécules immobiles et d'autres qui diffusent. L'analyse de la dynamique d'agrégation permettra de dégager certaines caractéristiques du mécanisme de photo-agrégation et d'appréhender le rôle joué par la matrice sol-gel dans ce processus.

  6. Discrimination of thermal diffusivity

    NARCIS (Netherlands)

    Bergmann Tiest, W.M.; Kappers, A.M.L.

    2009-01-01

    Materials such as wood or metal which are at equal temperatures are perceived to be of different ‘coldness’ due to differences in thermal properties, such as the thermal diffusivity. The thermal diffusivity of a material is a parameter that controls the rate with which heat is extracted from the

  7. Diffusion Based Photon Mapping

    DEFF Research Database (Denmark)

    Schjøth, Lars; Fogh Olsen, Ole; Sporring, Jon

    2007-01-01

    . To address this problem we introduce a novel photon mapping algorithm based on nonlinear anisotropic diffusion. Our algorithm adapts according to the structure of the photon map such that smoothing occurs along edges and structures and not across. In this way we preserve the important illumination features......, while eliminating noise. We call our method diffusion based photon mapping....

  8. Diffusion Based Photon Mapping

    DEFF Research Database (Denmark)

    Schjøth, Lars; Olsen, Ole Fogh; Sporring, Jon

    2006-01-01

    . To address this problem we introduce a novel photon mapping algorithm based on nonlinear anisotropic diffusion. Our algorithm adapts according to the structure of the photon map such that smoothing occurs along edges and structures and not across. In this way we preserve the important illumination features......, while eliminating noise. We call our method diffusion based photon mapping....

  9. Adaptation and Cultural Diffusion.

    Science.gov (United States)

    Ormrod, Richard K.

    1992-01-01

    Explores the role of adaptation in cultural diffusion. Explains that adaptation theory recognizes the lack of independence between innovations and their environmental settings. Discusses testing and selection, modification, motivation, and cognition. Suggests that adaptation effects are pervasive in cultural diffusion but require a broader, more…

  10. Modelling of Innovation Diffusion

    Directory of Open Access Journals (Sweden)

    Arkadiusz Kijek

    2010-01-01

    Full Text Available Since the publication of the Bass model in 1969, research on the modelling of the diffusion of innovation resulted in a vast body of scientific literature consisting of articles, books, and studies of real-world applications of this model. The main objective of the diffusion model is to describe a pattern of spread of innovation among potential adopters in terms of a mathematical function of time. This paper assesses the state-of-the-art in mathematical models of innovation diffusion and procedures for estimating their parameters. Moreover, theoretical issues related to the models presented are supplemented with empirical research. The purpose of the research is to explore the extent to which the diffusion of broadband Internet users in 29 OECD countries can be adequately described by three diffusion models, i.e. the Bass model, logistic model and dynamic model. The results of this research are ambiguous and do not indicate which model best describes the diffusion pattern of broadband Internet users but in terms of the results presented, in most cases the dynamic model is inappropriate for describing the diffusion pattern. Issues related to the further development of innovation diffusion models are discussed and some recommendations are given. (original abstract

  11. Thermal diffusion (1963)

    International Nuclear Information System (INIS)

    Lemarechal, A.

    1963-01-01

    This report brings together the essential principles of thermal diffusion in the liquid and gaseous phases. The macroscopic and molecular aspects of the thermal diffusion constant are reviewed, as well as the various measurement method; the most important developments however concern the operation of the CLUSIUS and DICKEL thermo-gravitational column and its applications. (author) [fr

  12. Diffusion of Botulinum Toxins

    Directory of Open Access Journals (Sweden)

    Matthew A. Brodsky

    2012-08-01

    Full Text Available Background: It is generally agreed that diffusion of botulinum toxin occurs, but the extent of the spread and its clinical importance are disputed. Many factors have been suggested to play a role but which have the most clinical relevance is a subject of much discussion.Methods: This review discusses the variables affecting diffusion, including protein composition and molecular size as well as injection factors (e.g., volume, dose, injection method. It also discusses data on diffusion from comparative studies in animal models and human clinical trials that illustrate differences between the available botulinum toxin products (onabotulinumtoxinA, abobotulinumtoxinA, incobotulinumtoxinA, and rimabotulinumtoxinB.Results: Neither molecular weight nor the presence of complexing proteins appears to affect diffusion; however, injection volume, concentration, and dose all play roles and are modifiable. Both animal and human studies show that botulinum toxin products are not interchangeable, and that some products are associated with greater diffusion and higher rates of diffusion-related adverse events than others.Discussion: Each of the botulinum toxins is a unique pharmacologic entity. A working knowledge of the different serotypes is essential to avoid unwanted diffusion-related adverse events. In addition, clinicians should be aware that the factors influencing diffusion may range from properties intrinsic to the drug to accurate muscle selection as well as dilution, volume, and dose injected.

  13. Diffusion with social reinforcement: The role of individual preferences

    Science.gov (United States)

    Tur, Elena M.; Zeppini, Paolo; Frenken, Koen

    2018-02-01

    The debate on diffusion in social networks has traditionally focused on the structure of the network to understand the efficiency of a network in terms of diffusion. Recently, the role of social reinforcement has been added to the debate, as it has been proposed that simple contagions diffuse better in random networks and complex contagions diffuse better in regular networks. In this paper, we show that individual preferences cannot be overlooked: complex contagions diffuse better in regular networks only if the large majority of the population is biased against adoption.

  14. Diffusion in Coulomb crystals.

    Science.gov (United States)

    Hughto, J; Schneider, A S; Horowitz, C J; Berry, D K

    2011-07-01

    Diffusion in Coulomb crystals can be important for the structure of neutron star crusts. We determine diffusion constants D from molecular dynamics simulations. We find that D for Coulomb crystals with relatively soft-core 1/r interactions may be larger than D for Lennard-Jones or other solids with harder-core interactions. Diffusion, for simulations of nearly perfect body-centered-cubic lattices, involves the exchange of ions in ringlike configurations. Here ions "hop" in unison without the formation of long lived vacancies. Diffusion, for imperfect crystals, involves the motion of defects. Finally, we find that diffusion, for an amorphous system rapidly quenched from Coulomb parameter Γ=175 to Coulomb parameters up to Γ=1750, is fast enough that the system starts to crystalize during long simulation runs. These results strongly suggest that Coulomb solids in cold white dwarf stars, and the crust of neutron stars, will be crystalline and not amorphous.

  15. Degenerate nonlinear diffusion equations

    CERN Document Server

    Favini, Angelo

    2012-01-01

    The aim of these notes is to include in a uniform presentation style several topics related to the theory of degenerate nonlinear diffusion equations, treated in the mathematical framework of evolution equations with multivalued m-accretive operators in Hilbert spaces. The problems concern nonlinear parabolic equations involving two cases of degeneracy. More precisely, one case is due to the vanishing of the time derivative coefficient and the other is provided by the vanishing of the diffusion coefficient on subsets of positive measure of the domain. From the mathematical point of view the results presented in these notes can be considered as general results in the theory of degenerate nonlinear diffusion equations. However, this work does not seek to present an exhaustive study of degenerate diffusion equations, but rather to emphasize some rigorous and efficient techniques for approaching various problems involving degenerate nonlinear diffusion equations, such as well-posedness, periodic solutions, asympt...

  16. Probing the diffuse interstellar medium with diffuse interstellar bands

    Science.gov (United States)

    Theodorus van Loon, Jacco; Bailey, Mandy; Farhang, Amin; Javadi, Atefeh; Khosroshahi, Habib

    2015-08-01

    For a century already, a large number of absorption bands have been known at optical wavelengths, called the diffuse interstellar bands (DIBs). While their carriers remain unidentified, the relative strengths of these bands in various environments make them interesting new probes of the diffuse interstellar medium (ISM). We present the results from two large, dedicated campaigns to map the ISM using DIBs measured in the high signal-to-noise spectra of hundreds of early-type stars: [1] in and around the Local Bubble using ESO's New Technology Telescope and the Isaac Newton Telescope, and [2] across both Magellanic Clouds using the Very Large Telescope and the Anglo-Australian Telescope. We discuss the implications for the structure and dynamics of the ISM, as well as the constraints these maps place on the nature of the carriers of the DIBs. Partial results have appeared in the recent literature (van Loon et al. 2013; Farhang et al. 2015a,b; Bailey, PhD thesis 2014) with the remainder being prepared for publication now.

  17. Oxygen diffusion in monazite

    Science.gov (United States)

    Cherniak, D. J.; Zhang, X. Y.; Nakamura, M.; Watson, E. B.

    2004-09-01

    We report measurements of oxygen diffusion in natural monazites under both dry, 1-atm conditions and hydrothermal conditions. For dry experiments, 18O-enriched CePO4 powder and monazite crystals were sealed in Ag-Pd capsules with a solid buffer (to buffer at NNO) and annealed in 1-atm furnaces. Hydrothermal runs were conducted in cold-seal pressure vessels, where monazite grains were encapsulated with 18O-enriched water. Following the diffusion anneals, oxygen concentration profiles were measured with Nuclear Reaction Analysis (NRA) using the reaction 18O(p,α)15N. Over the temperature range 850-1100 °C, the Arrhenius relation determined for dry diffusion experiments on monazite is given by: Under wet conditions at 100 MPa water pressure, over the temperature range 700-880 °C, oxygen diffusion can be described by the Arrhenius relationship: Oxygen diffusion under hydrothermal conditions has a significantly lower activation energy for diffusion than under dry conditions, as has been found the case for many other minerals, both silicate and nonsilicate. Given these differences in activation energies, the differences between dry and wet diffusion rates increase with lower temperatures; for example, at 600 °C, dry diffusion will be more than 4 orders of magnitude slower than diffusion under hydrothermal conditions. These disparate diffusivities will result in pronounced differences in the degree of retentivity of oxygen isotope signatures. For instance, under dry conditions (presumably rare in the crust) and high lower-crustal temperatures (∼800 °C), monazite cores of 70-μm radii will preserve O isotope ratios for about 500,000 years; by comparison, they would be retained at this temperature under wet conditions for about 15,000 years.

  18. EBV-positive B cell cerebral lymphoma 12 years after sex-mismatched kidney transplantation: post-transplant lymphoproliferative disorder or donor-derived lymphoma?

    LENUS (Irish Health Repository)

    Phelan, Paul J

    2010-06-01

    We present a follow-up case report of possible transmission of lymphoma 12 years after deceased-donor renal transplantation from a male donor who was found at autopsy to have had an occult lymphoma. The female recipient underwent prompt transplant nephrectomy. However, 12 years later, she presented with cerebral B cell lymphoma. A donor origin for the cerebral lymphoma was supported by in situ hybridization demonstration of a Y chromosome in the lymphoma. There was a dramatic resolution of the cerebral lesions with tapering of immunosuppression and introduction of rituximab treatment. The finding of a Y chromosome in the cerebral lymphoma does not exclude a host contribution to lymphoma development.

  19. Primary EBV-positive Hodgkin's lymphoma of the CNS under azathioprine treatment. Case report and review of the literature

    Energy Technology Data Exchange (ETDEWEB)

    Henkenberens, Christoph; Christiansen, Hans [Medizinische Hochschule Hannover, Klinik fuer Strahlentherapie und Spezielle Onkologie, Hannover (Germany); Franzke, Anke [Medizinische Hochschule Hannover, Klinik fuer Haematologie, Haemostaseologie, Onkologie und Stammzelltransplantation, Hannover (Germany); Raab, Peter [Medizinische Hochschule Hannover, Institut fuer Diagnostische und Interventionelle Neuroradiologie, Hannover (Germany); Oschlies, Ilske; Klapper, Wolfram [Universitaetsklinikum Schleswig-Holstein, Institut fuer Pathologie, Sektion Haematopathologie, Kiel (Germany)

    2014-09-15

    Retrospective and prospective cohort studies suggest that central nervous system involvement occurs in approximately 0.5 % of patients with advanced Hodgkin's lymphoma. The isolated primary intracranial manifestation of Hodgkin's lymphoma is an extremely rare finding, with few cases reported in the literature. Little is known about the optimal treatment and prognosis of these tumors. Here, we present a case report with a review of the literature. A 47-year-old Caucasian man with persistent frontal headache and unspecific vertigo for half a month was diagnosed with nodular space-occupying lesions in the cerebellum. His medical history included multiple sclerosis, which was treated for 20 years with the immunosuppressive drug azathioprine. Further staging revealed no additional lesions suspected of being malignant. The patient underwent total tumor resection. Immunohistopathological examination showed Epstein-Barr virus-associated classic Hodgkin's lymphoma. Diagnostic bone marrow punction excluded lymphoma involvement of the bone marrow. The patient had no B symptoms. Consequently, the patient was classified as having stage I{sub E}A disease according to the Modified Ann Arbor Classification of Hodgkin Lymphoma and received systemic chemotherapy followed by radiation therapy for the former cerebellar tumor region. He was in complete clinical remission at the last follow-up 9 months after the initial diagnosis. This case report and literature review suggest that multimodal treatment leads to a remarkable clinical outcome in Hodgkin's lymphoma with intracranial involvement. (orig.) [German] Retrospektive und prospektive Kohortenstudien deuten daraufhin, dass eine Beteiligung des zentralen Nervensystems (ZNS) in etwa bei 0,5 % der Patienten mit fortgeschrittenem Hodgkin-Lymphom auftritt. Die isoliert primaer intrakranielle Manifestation des Hodgkin-Lymphoms ist extrem selten, mit wenigen bisher bekannten Faellen. Wenig ist auch ueber die optimale Therapie und Prognose dieser seltenen Entitaet bekannt. Wir praesentieren einen entsprechenden Fallbericht mit einer Literaturuebersicht. Ein 47-jaehriger Kaukasier mit persistierendem Stirnkopfschmerz und unspezifischem Schwindel praesentierte in radiologischen Untersuchungen mehrere nodulaere Raumforderungen im Kleinhirn mit Kontakt zum 4. Ventrikel. Seine Krankengeschichte umfasste eine Multiple Sklerose, die seit 20 Jahren mit dem Immunsuppressivum Azathioprin behandelt wurde. Das weitere Staging ergab keine weiteren malignitaetsverdaechtigen Laesionen. Die tumoroesen Laesionen wurden vollstaendig reseziert. Die Immunhistopathologie zeigte ein Epstein-Barr-Virus-assoziiertes klassisches Hodgkin-Lymphom. Die diagnostische Knochenmarkpunktion ergab keinen Hinweis auf eine Lymphombeteiligung. Der Patient zeigte keine B-Symptome. Somit wurde die Lymphomerkrankung des Patienten als Stadium IE A nach der modifizierten Ann-Arbor-Klassifikation fuer Hodgkin-Lymphome klassifiziert. Der Patient erhielt postoperativ eine Chemotherapie gefolgt von einer Bestrahlung der ehemaligen Tumorregion des Kleinhirns. Er erreichte eine Komplettremission, die in der letzten Follow-up-Untersuchung nach 9 Monaten weiter anhielt. Dieser Fallbericht und die Literaturuebersicht legen nahe, dass eine multimodale Behandlung zu guten klinischen Ergebnissen bei primaer intrakraniellem Hodgkin-Lymphom fuehrt. (orig.)

  20. Helium diffusion in nickel at high temperatures

    International Nuclear Information System (INIS)

    Philipps, V.

    1980-09-01

    Helium has been implanted at certain temperatures between 800 and 1250 0 C into single and polycrystalline Ni-samples with implantation depths between 15 and 90 μm. Simultaneously the helium reemission from the sample is measured by a mass-spectrometer. It has been shown that the time dependence of the observed reemission rate is governed by volume diffusion of the helium. Measuring this time dependence as a function of temperature the helium diffusion constant has been determined. The He-diffusion is interpreted as a interstitial diffusion hindered by thermal vacancies. Depending on the implantation depth more or less of the implanted helium remains in the sample and forms large helium bubbles. (orig./GSCH)

  1. Diffusion Indexes with Sparse Loadings

    DEFF Research Database (Denmark)

    Kristensen, Johannes Tang

    The use of large-dimensional factor models in forecasting has received much attention in the literature with the consensus being that improvements on forecasts can be achieved when comparing with standard models. However, recent contributions in the literature have demonstrated that care needs...... to the problem by using the LASSO as a variable selection method to choose between the possible variables and thus obtain sparse loadings from which factors or diffusion indexes can be formed. This allows us to build a more parsimonious factor model which is better suited for forecasting compared...... it to be an important alternative to PC....

  2. Diffuse interstellar clouds

    International Nuclear Information System (INIS)

    Black, J.H.

    1987-01-01

    The author defines and discusses the nature of diffuse interstellar clouds. He discusses how they contribute to the general extinction of starlight. The atomic and molecular species that have been identified in the ultraviolet, visible, and near infrared regions of the spectrum of a diffuse cloud are presented. The author illustrates some of the practical considerations that affect absorption line observations of interstellar atoms and molecules. Various aspects of the theoretical description of diffuse clouds required for a full interpretation of the observations are discussed

  3. Infrared diffuse interstellar bands

    Science.gov (United States)

    Galazutdinov, G. A.; Lee, Jae-Joon; Han, Inwoo; Lee, Byeong-Cheol; Valyavin, G.; Krełowski, J.

    2017-05-01

    We present high-resolution (R ˜ 45 000) profiles of 14 diffuse interstellar bands in the ˜1.45 to ˜2.45 μm range based on spectra obtained with the Immersion Grating INfrared Spectrograph at the McDonald Observatory. The revised list of diffuse bands with accurately estimated rest wavelengths includes six new features. The diffuse band at 15 268.2 Å demonstrates a very symmetric profile shape and thus can serve as a reference for finding the 'interstellar correction' to the rest wavelength frame in the H range, which suffers from a lack of known atomic/molecular lines.

  4. Self diffusion in tungsten

    International Nuclear Information System (INIS)

    Mundy, J.N.; Rothman, S.J.; Lam, N.Q.; Nowicki, L.J.; Hoff, H.A.

    1978-01-01

    The lack of understanding of self-diffusion in Group VI metals together with the wide scatter in the measured values of tungsten self-diffusion has prompted the present measurements to be made over a wide temperature range (1/2Tsub(m) to Tsub(m)). The diffusion coefficients have been measured in the temperature range 1430-2630 0 C. The present measurements show non-linear Arrhenius behavior but a reliable two-exponential fit of the data should await further measurements. (Auth.)

  5. Diffusion of Wilson loops

    International Nuclear Information System (INIS)

    Brzoska, A.M.; Lenz, F.; Thies, M.; Negele, J.W.

    2005-01-01

    A phenomenological analysis of the distribution of Wilson loops in SU(2) Yang-Mills theory is presented in which Wilson loop distributions are described as the result of a diffusion process on the group manifold. It is shown that, in the absence of forces, diffusion implies Casimir scaling and, conversely, exact Casimir scaling implies free diffusion. Screening processes occur if diffusion takes place in a potential. The crucial distinction between screening of fundamental and adjoint loops is formulated as a symmetry property related to the center symmetry of the underlying gauge theory. The results are expressed in terms of an effective Wilson loop action and compared with various limits of SU(2) Yang-Mills theory

  6. Diffusion between evolving interfaces

    International Nuclear Information System (INIS)

    Juntunen, Janne; Merikoski, Juha

    2010-01-01

    Diffusion in an evolving environment is studied by continuous-time Monte Carlo simulations. Diffusion is modeled by continuous-time random walkers on a lattice, in a dynamic environment provided by bubbles between two one-dimensional interfaces driven symmetrically towards each other. For one-dimensional random walkers constrained by the interfaces, the bubble size distribution dominates diffusion. For two-dimensional random walkers, it is also controlled by the topography and dynamics of the interfaces. The results of the one-dimensional case are recovered in the limit where the interfaces are strongly driven. Even with simple hard-core repulsion between the interfaces and the particles, diffusion is found to depend strongly on the details of the dynamical rules of particles close to the interfaces.

  7. On Diffusion and Permeation

    KAUST Repository

    Peppin, Stephen S. L.

    2009-01-01

    concentrations they form a nearly rigid porous glass through which the fluid permeates. The theoretically determined pressure drop is nonlinear in the diffusion regime and linear in the permeation regime, in quantitative agreement with experimental measurements

  8. Diffusing Best Practices

    DEFF Research Database (Denmark)

    Pries-Heje, Jan; Baskerville, Richard

    2014-01-01

    approach. The study context is a design case in which an organization desires to diffuse its best practices across different groups. The design goal is embodied in organizational mechanisms to achieve this diffusion. The study used Theory of Planned Behavior (TPB) as a kernel theory. The artifacts...... resulting from the design were two-day training workshops conceptually anchored to TBP. The design theory was evaluated through execution of eight diffusion workshops involving three different groups in the same company. The findings indicate that the match between the practice and the context materialized...... that the behavior will be effective). These two factors were especially critical if the source context of the best practice is qualitatively different from the target context into which the organization is seeking to diffuse the best practice....

  9. Detection of diffusible substances

    Energy Technology Data Exchange (ETDEWEB)

    Warembourg, M [Lille-1 Univ., 59 - Villeneuve-d' Ascq (France)

    1976-12-01

    The different steps of a radioautographic technique for the detection of diffusible substances are described. Using this radioautographic method, the topographic distribution of estradiol-concentrating neurons was studied in the nervous system and pituitary of the ovariectomized mouse and guinea-pig. A relatively good morphological preservation of structures can be ascertained on sections from unfixed, unembedded tissues prepared at low temperatures and kept-under relatively low humidity. The translocation or extraction of diffusible substances is avoided by directly mounting of frozen sections on dried photographic emulsion. Since no solvent is used, this technique excludes the major sources of diffusion artifacts and permits to be in favourable conditions for the localization of diffusible substances.

  10. On Diffusion and Permeation

    KAUST Repository

    Peppin, Stephen S. L.

    2009-01-01

    Diffusion and permeation are discussed within the context of irreversible thermodynamics. A new expression for the generalized Stokes-Einstein equation is obtained which links the permeability to the diffusivity of a two-component solution and contains the poroelastic Biot-Willis coefficient. The theory is illustrated by predicting the concentration and pressure profiles during the filtration of a protein solution. At low concentrations the proteins diffuse independently while at higher concentrations they form a nearly rigid porous glass through which the fluid permeates. The theoretically determined pressure drop is nonlinear in the diffusion regime and linear in the permeation regime, in quantitative agreement with experimental measurements. © 2009 Walter de Gruyter, Berlin, New York.

  11. Drift-Diffusion Equation

    Directory of Open Access Journals (Sweden)

    K. Banoo

    1998-01-01

    equation in the discrete momentum space. This is shown to be similar to the conventional drift-diffusion equation except that it is a more rigorous solution to the Boltzmann equation because the current and carrier densities are resolved into M×1 vectors, where M is the number of modes in the discrete momentum space. The mobility and diffusion coefficient become M×M matrices which connect the M momentum space modes. This approach is demonstrated by simulating electron transport in bulk silicon.

  12. Advanced manufacturing: Technology diffusion

    Energy Technology Data Exchange (ETDEWEB)

    Tesar, A.

    1995-12-01

    In this paper we examine how manufacturing technology diffuses rom the developers of technology across national borders to those who do not have the capability or resources to develop advanced technology on their own. None of the wide variety of technology diffusion mechanisms discussed in this paper are new, yet the opportunities to apply these mechanisms are growing. A dramatic increase in technology diffusion occurred over the last decade. The two major trends which probably drive this increase are a worldwide inclination towards ``freer`` markets and diminishing isolation. Technology is most rapidly diffusing from the US In fact, the US is supplying technology for the rest of the world. The value of the technology supplied by the US more than doubled from 1985 to 1992 (see the Introduction for details). History shows us that technology diffusion is inevitable. It is the rates at which technologies diffuse to other countries which can vary considerably. Manufacturers in these countries are increasingly able to absorb technology. Their manufacturing efficiency is expected to progress as technology becomes increasingly available and utilized.

  13. Now consider diffusion

    International Nuclear Information System (INIS)

    Dungey, J.W.

    1984-01-01

    The authors want to talk about future work, but first he will reply to Stan Cowley's comment on his naivety in believing in the whole story to 99% confidence in '65, when he knew about Fairfield's results. Does it matter whether you make the right judgment about theories? Yes, it does, particularly for experimentalists perhaps, but also for theorists. The work you do later depends on the judgment you've made on previous work. People have wasted a lot of time developing on insecure or even wrong foundations. Now for future work. One mild surprise the authors have had is that they haven't heard more about diffusion, in two contexts. Gordon Rostoker is yet to come and he may talk about particles getting into the magnetosphere by diffusion. Lots of noise is observed and so diffusion must happen. If time had not been short, the authors were planning to discuss in a handwaving way what sort of diffusion mechanisms one might consider. The other aspect of diffusion he was going to talk about is at the other end of things and is velocity diffusion, which is involved in anomalous resistivity

  14. Nonlinear degenerate cross-diffusion systems with nonlocal interaction

    OpenAIRE

    Di Francesco, M.; Esposito, A.; Fagioli, S.

    2017-01-01

    We investigate a class of systems of partial differential equations with nonlinear cross-diffusion and nonlocal interactions, which are of interest in several contexts in social sciences, finance, biology, and real world applications. Assuming a uniform "coerciveness" assumption on the diffusion part, which allows to consider a large class of systems with degenerate cross-diffusion (i.e. of porous medium type) and relaxes sets of assumptions previously considered in the literature, we prove g...

  15. Sentiment classification with interpolated information diffusion kernels

    NARCIS (Netherlands)

    Raaijmakers, S.

    2007-01-01

    Information diffusion kernels - similarity metrics in non-Euclidean information spaces - have been found to produce state of the art results for document classification. In this paper, we present a novel approach to global sentiment classification using these kernels. We carry out a large array of

  16. Lead diffusion in monazite

    International Nuclear Information System (INIS)

    Gardes, E.

    2006-06-01

    Proper knowledge of the diffusion rates of lead in monazite is necessary to understand the U-Th-Pb age anomalies of this mineral, which is one of the most used in geochronology after zircon. Diffusion experiments were performed in NdPO 4 monocrystals and in Nd 0.66 Ca 0.17 Th 0.17 PO 4 polycrystals from Nd 0.66 Pb 0.17 Th 0.17 PO 4 thin films to investigate Pb 2+ + Th 4+ ↔ 2 Nd 3+ and Pb 2+ ↔ Ca 2+ exchanges. Diffusion annealings were run between 1200 and 1500 Celsius degrees, at room pressure, for durations ranging from one hour to one month. The diffusion profiles were analysed using TEM (transmission electronic microscopy) and RBS (Rutherford backscattering spectroscopy). The diffusivities extracted for Pb 2+ + Th 4+ ↔ 2 Nd 3+ exchange follow an Arrhenius law with parameters E equals 509 ± 24 kJ mol -1 and log(D 0 (m 2 s -1 )) equals -3.41 ± 0.77. Preliminary data for Pb 2+ ↔ Ca 2+ exchange are in agreement with this result. The extrapolation of our data to crustal temperatures yields very slow diffusivities. For instance, the time necessary for a 50 μm grain to lose all of its lead at 800 Celsius degrees is greater than the age of the Earth. From these results and other evidence from the literature, we conclude that most of the perturbations in U-Th-Pb ages of monazite cannot be attributed to lead diffusion, but rather to interactions with fluids. (author)

  17. Diffuse corpus callosum infarction - Rare vascular entity with differing etiology.

    Science.gov (United States)

    Mahale, Rohan; Mehta, Anish; Buddaraju, Kiran; John, Aju Abraham; Javali, Mahendra; Srinivasa, Rangasetty

    2016-01-15

    Infarctions of the corpus callosum are rare vascular events. It is relatively immune to vascular insult because of its rich vascular supply from anterior and posterior circulations of brain. Report of 3 patients with largely diffuse acute corpus callosum infarction. 3 patients with largely diffuse acute corpus callosum infarction were studied and each of these 3 patients had 3 different aetiologies. The 3 different aetiologies of largely diffuse acute corpus callosum infarction were cardioembolism, tuberculous arteritis and takayasu arteritis. Diffuse corpus callosum infarcts are rare events. This case series narrates the three different aetiologies of diffuse acute corpus callosum infarction which is a rare vascular event. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Optimal Design for the Diffusion Plate with Nanoparticles in a Diffusive Solar Cell Window by Mie Scattering Simulation

    Directory of Open Access Journals (Sweden)

    Ruei-Tang Chen

    2013-01-01

    Full Text Available A diffusive solar cell window comprises a diffusion plate with TiO2 nanoparticles sandwiched between two glass layers. It is a simple, inexpensive, easy-to-made, and highly reliable transparent solar energy module. To improve its power generation efficiency as well as maintain indoor natural lighting, we examined the scattering mechanism in the diffusion plate with TiO2 nanoparticles within a diffusive solar cell window by Mie scattering simulations. In this work, a multiwavelength ASAP ray tracing model for a diffusive solar cell window with acceptable accuracy was developed to investigate the influence of the diffusion plate design parameter, mainly concentration of a diffusion plate with determined particle size distribution, on power generation efficiency and color shift of transmitted sun light. A concept of “effective average radius” was proposed to account for the equivalent scattering effect of a size distribution of quasispherical particles. Simulation results demonstrated that both the transmitted light and its correlated color temperature decreased as the concentration increased for a large-size diffusive solar cell window. However, there existed a maximum power generation efficiency at around 160 ppm concentration. The optimal design for a large-size diffusion plate inside a diffusive solar cell window by taking indoor lighting into account was suggested based on the simulation results.

  19. Diffusion of protein through the human cornea.

    Science.gov (United States)

    Charalel, Resmi A; Engberg, Kristin; Noolandi, Jaan; Cochran, Jennifer R; Frank, Curtis; Ta, Christopher N

    2012-01-01

    To determine the rate of diffusion of myoglobin and bovine serum albumin (BSA) through the human cornea. These small proteins have hydrodynamic diameters of approximately 4.4 and 7.2 nm, and molecular weights of 16.7 and 66 kDa, for myoglobin and BSA, respectively. Diffusion coefficients were measured using a diffusion chamber where the protein of interest and balanced salt solution were in different chambers separated by an ex vivo human cornea. Protein concentrations in the balanced salt solution chamber were measured over time. Diffusion coefficients were calculated using equations derived from Fick's law and conservation of mass in a closed system. Our experiments demonstrate that the diffusion coefficient of myoglobin is 5.5 ± 0.9 × 10(-8) cm(2)/s (n = 8; SD = 1.3 × 10(-8) cm(2)/s; 95% CI: 4.6 × 10(-8) to 6.4 × 10(-8) cm(2)/s) and the diffusion coefficient of BSA is 3.1 ± 1.0 × 10(-8) cm(2)/s (n = 8; SD = 1.4 × 10(-8) cm(2)/s; 95% CI: 2.1 × 10(-8) to 4.1 × 10(-8) cm(2)/s). Our study suggests that molecules as large as 7.2 nm may be able to passively diffuse through the human cornea. With applications in pharmacotherapy and the development of an artificial cornea, further experiments are warranted to fully understand the limits of human corneal diffusion and its clinical relevance. Copyright © 2012 S. Karger AG, Basel.

  20. Diffusion Influenced Adsorption Kinetics.

    Science.gov (United States)

    Miura, Toshiaki; Seki, Kazuhiko

    2015-08-27

    When the kinetics of adsorption is influenced by the diffusive flow of solutes, the solute concentration at the surface is influenced by the surface coverage of solutes, which is given by the Langmuir-Hinshelwood adsorption equation. The diffusion equation with the boundary condition given by the Langmuir-Hinshelwood adsorption equation leads to the nonlinear integro-differential equation for the surface coverage. In this paper, we solved the nonlinear integro-differential equation using the Grünwald-Letnikov formula developed to solve fractional kinetics. Guided by the numerical results, analytical expressions for the upper and lower bounds of the exact numerical results were obtained. The upper and lower bounds were close to the exact numerical results in the diffusion- and reaction-controlled limits, respectively. We examined the validity of the two simple analytical expressions obtained in the diffusion-controlled limit. The results were generalized to include the effect of dispersive diffusion. We also investigated the effect of molecular rearrangement of anisotropic molecules on surface coverage.

  1. Bicarbonate diffusion through mucus.

    Science.gov (United States)

    Livingston, E H; Miller, J; Engel, E

    1995-09-01

    The mucus layer overlying duodenal epithelium maintains a pH gradient against high luminal acid concentrations. Despite these adverse conditions, epithelial surface pH remains close to neutrality. The exact nature of the gradient-forming barrier remains unknown. The barrier consists of mucus into which HCO3- is secreted. Quantification of the ability of HCO3- to establish and maintain the gradient depends on accurate measurement of this ion's diffusion coefficient through mucus. We describe new experimental and mathematical methods for diffusion measurement and report diffusion coefficients for HCO3- diffusion through saline, 5% mucin solutions, and rat duodenal mucus. The diffusion coefficients were 20.2 +/- 0.10, 3.02 +/- 0.31, and 1.81 +/- 0.12 x 10(-6) cm2/s, respectively. Modeling of the mucobicarbonate layer with this latter value suggests that for conditions of high luminal acid strength the neutralization of acid by HCO3- occurs just above the epithelial surface. Under these conditions the model predicts that fluid convection toward the lumen could be important in maintaining the pH gradient. In support of this hypothesis we were able to demonstrate a net luminal fluid flux of 5 microliters.min-1.cm-2 after perfusion of 0.15 N HCl in the rat duodenum.

  2. Simple Brownian diffusion an introduction to the standard theoretical models

    CERN Document Server

    Gillespie, Daniel T

    2013-01-01

    Brownian diffusion, the motion of large molecules in a sea of very many much smaller molecules, is topical because it is one of the ways in which biologically important molecules move about inside living cells. This book presents the mathematical physics that underlies the four simplest models of Brownian diffusion.

  3. Uranium enrichment by the gaseous diffusion process

    International Nuclear Information System (INIS)

    Petit, J.F.

    1977-01-01

    After a brief description of the process and technology (principle, stage constitution, cascade constitution, and description of a plant), the author gives the history of gaseous diffusion and describes the existing facilities. Among the different enrichment processes contemplated in the USA during and after the last world war, gaseous diffusion has been the only one to be developed industrially on a wide scale in the USA, then in the UK, in the USSR and in France. The large existing capacities in the USA provided the country with a good starting base for the development of a light-water nuclear power plant programme, the success of which led to a shortfall in production means. France and the USA, possessing the necessary know-how, have been able to undertake the realization of two industrial programmes: the CIP-CUP programme in the USA and the Eurodif project in France. Current plans still call for the construction of several plants by 1990. Can the gaseous diffusion process meet this challenge. Technically, there is no doubt about it. Economically, this process is mainly characterized by large energy consumption and the necessity to build large plants. This leads to a large investment, at least for the first plant. Other processes have been developed with a view to reducing both energy and capital needs. However, in spite of continuous studies and technological progress, no process has yet proved competitive. Large increments in capacities are still expected to come from gaseous diffusion, and several projects taking into account the improvements in flexibility, automatization, reliability and reduced investment, are analysed in the paper. Combining new facilities with existing plants has already proved to be of great interest. This situation explains why gaseous diffusion is being further investigated and new processes are being studied. (author)

  4. Cesium diffusion in graphite

    International Nuclear Information System (INIS)

    Evans, R.B. III; Davis, W. Jr.; Sutton, A.L. Jr.

    1980-05-01

    Experiments on diffusion of 137 Cs in five types of graphite were performed. The document provides a completion of the report that was started and includes a presentation of all of the diffusion data, previously unpublished. Except for data on mass transfer of 137 Cs in the Hawker-Siddeley graphite, analyses of experimental results were initiated but not completed. The mass transfer process of cesium in HS-1-1 graphite at 600 to 1000 0 C in a helium atmosphere is essentially pure diffusion wherein values of (E/epsilon) and ΔE of the equation D/epsilon = (D/epsilon) 0 exp [-ΔE/RT] are about 4 x 10 -2 cm 2 /s and 30 kcal/mole, respectively

  5. Apparatus for diffusion separation

    International Nuclear Information System (INIS)

    Nierenberg, W.A.; Pontius, R.B.

    1976-01-01

    The method of testing the separation efficiency of porous permeable membranes is described which comprises causing a stream of a gaseous mixture to flow into contact with one face of a finely porous permeable membrane under such conditions that a major fraction of the mixture diffuses through the membrane, maintaining a rectangular cross section of the gaseous stream so flowing past said membrane, continuously recirculating the gas that diffuses through said membrane and continuously withdrawing the gas that does not diffuse through said membrane and maintaining the volume of said recirculating gas constant by continuously introducing into said continuously recirculating gas stream a mass of gas equivalent to that which is continuously withdrawn from said gas stream and comparing the concentrations of the light component in the entering gas, the withdrawn gas and the recirculated gas in order to determine the efficiency of said membrane

  6. Diffusion in flexible pipes

    Energy Technology Data Exchange (ETDEWEB)

    Brogaard Kristensen, S.

    2000-06-01

    This report describes the work done on modelling and simulation of the complex diffusion of gas through the wall of a flexible pipe. The diffusion and thus the pressure in annulus depends strongly on the diffusion and solubility parameters of the gas-polymer system and on the degree of blocking of the outer surface of the inner liner due to pressure reinforcements. The report evaluates the basis modelling required to describe the complex geometries and flow patterns. Qualitatively results of temperature and concentration profiles are shown in the report. For the program to serve any modelling purpose in 'real life' the results need to be validated and possibly the model needs corrections. Hopefully, a full-scale test of a flexible pipe will provide the required temperatures and pressures in annulus to validate the models. (EHS)

  7. Distributed Control Diffusion

    DEFF Research Database (Denmark)

    Schultz, Ulrik Pagh

    2007-01-01

    . Programming a modular, self-reconfigurable robot is however a complicated task: the robot is essentially a real-time, distributed embedded system, where control and communication paths often are tightly coupled to the current physical configuration of the robot. To facilitate the task of programming modular....... This approach allows the programmer to dynamically distribute behaviors throughout a robot and moreover provides a partial abstraction over the concrete physical shape of the robot. We have implemented a prototype of a distributed control diffusion system for the ATRON modular, self-reconfigurable robot......, self-reconfigurable robots, we present the concept of distributed control diffusion: distributed queries are used to identify modules that play a specific role in the robot, and behaviors that implement specific control strategies are diffused throughout the robot based on these role assignments...

  8. Diffuse Ceiling Ventilation

    DEFF Research Database (Denmark)

    Zhang, Chen; Yu, Tao; Heiselberg, Per Kvols

    cooling capacity, energy saving, low investment cost and low noise level; while the limitations include condensation risk and the limit on the room geometry. Furthermore, the crucial design parameters are summarized and their effects on the system performance are discussed. In addition to the stand...... is not well structured with this system. These become the motivations in developing the design guide. This design guide aims to establish a systematic understanding of diffuse ceiling ventilation and provide assistance in designing of such a system. The guide is targeted at design engineers, architects...... and manufacturers and the users of diffuse ceiling technology. The design guide introduces the principle and key characteristics of room air distribution with diffuse ceiling ventilation. It provides an overview of potential benefit and limitations of this technology. The benefits include high thermal comfort, high...

  9. Diffusion and mass transfer

    CERN Document Server

    Vrentas, James S

    2013-01-01

    The book first covers the five elements necessary to formulate and solve mass transfer problems, that is, conservation laws and field equations, boundary conditions, constitutive equations, parameters in constitutive equations, and mathematical methods that can be used to solve the partial differential equations commonly encountered in mass transfer problems. Jump balances, Green’s function solution methods, and the free-volume theory for the prediction of self-diffusion coefficients for polymer–solvent systems are among the topics covered. The authors then use those elements to analyze a wide variety of mass transfer problems, including bubble dissolution, polymer sorption and desorption, dispersion, impurity migration in plastic containers, and utilization of polymers in drug delivery. The text offers detailed solutions, along with some theoretical aspects, for numerous processes including viscoelastic diffusion, moving boundary problems, diffusion and reaction, membrane transport, wave behavior, sedime...

  10. Diffusion in flexible pipes

    Energy Technology Data Exchange (ETDEWEB)

    Brogaard Kristensen, S

    2000-06-01

    This report describes the work done on modelling and simulation of the complex diffusion of gas through the wall of a flexible pipe. The diffusion and thus the pressure in annulus depends strongly on the diffusion and solubility parameters of the gas-polymer system and on the degree of blocking of the outer surface of the inner liner due to pressure reinforcements. The report evaluates the basis modelling required to describe the complex geometries and flow patterns. Qualitatively results of temperature and concentration profiles are shown in the report. For the program to serve any modelling purpose in 'real life' the results need to be validated and possibly the model needs corrections. Hopefully, a full-scale test of a flexible pipe will provide the required temperatures and pressures in annulus to validate the models. (EHS)

  11. Nonlinear diffusion equations

    CERN Document Server

    Wu Zhuo Qun; Li Hui Lai; Zhao Jun Ning

    2001-01-01

    Nonlinear diffusion equations, an important class of parabolic equations, come from a variety of diffusion phenomena which appear widely in nature. They are suggested as mathematical models of physical problems in many fields, such as filtration, phase transition, biochemistry and dynamics of biological groups. In many cases, the equations possess degeneracy or singularity. The appearance of degeneracy or singularity makes the study more involved and challenging. Many new ideas and methods have been developed to overcome the special difficulties caused by the degeneracy and singularity, which

  12. Phase transformation and diffusion

    CERN Document Server

    Kale, G B; Dey, G K

    2008-01-01

    Given that the basic purpose of all research in materials science and technology is to tailor the properties of materials to suit specific applications, phase transformations are the natural key to the fine-tuning of the structural, mechanical and corrosion properties. A basic understanding of the kinetics and mechanisms of phase transformation is therefore of vital importance. Apart from a few cases involving crystallographic martensitic transformations, all phase transformations are mediated by diffusion. Thus, proper control and understanding of the process of diffusion during nucleation, g

  13. Ambipolar diffusion in plasma

    International Nuclear Information System (INIS)

    Silva, T.L. da.

    1987-01-01

    Is this thesis, a numerical method for the solution of the linear diffusion equation for a plasma containing two types of ions, with the possibility of charge exchange, has been developed. It has been shown that the decay time of the electron and ion densities is much smaller than that in a plasma containing only a single type of ion. A non-linear diffusion equation, which includes the effects of an external electric field varying linearly in time, to describe a slightly ionized plasma has also been developed. It has been verified that the decay of the electron density in the presence of such an electric field is very slow. (author)

  14. Nonlinear Cross-Diffusion with Size Exclusion

    KAUST Repository

    Burger, Martin

    2010-01-01

    The aim of this paper is to investigate the mathematical properties of a continuum model for diffusion of multiple species incorporating size exclusion effects. The system for two species leads to nonlinear cross-diffusion terms with double degeneracy, which creates significant novel challenges in the analysis of the system. We prove global existence of weak solutions and well-posedness of strong solutions close to equilibrium. We further study some asymptotics of the model, and in particular we characterize the large-time behavior of solutions. 2010 © Society for Industrial and Applied Mathematics.

  15. Diffusion induced by cyclotron resonance heating

    International Nuclear Information System (INIS)

    Riyopoulos, S.; Tajima, T.; Hatori, T.; Pfirsch, D.

    1985-09-01

    The wave induced particle transport during the ion cyclotron resonance heating is studied in collisionless toroidal plasmas. It is shown that the previously neglected non-conservation of the toroidal angular momentum IP/sub phi/ caused by the toroidal wave component E/sub phi/ is necessary to allow particle diffusion and yields the leading diffusive contribution. While the induced ion transport for the rf power in contemporary experiments is of the order of the neoclassical value, that of fast alpha particles is quite large if resonance is present

  16. Diffusion corrections to the hard pomeron

    CERN Document Server

    Ciafaloni, Marcello; Müller, A H; Ciafaloni, Marcello; Taiuti,