Science.gov

Sample records for aids-related diffuse large

  1. Treatment outcomes in AIDS-related diffuse large B-cell lymphoma in the setting roll-out of combination antiretroviral therapy in South Africa

    PubMed Central

    de Witt, Pieter; Maartens, Deborah J; Uldrick, Thomas S; Sissolak, Gerhard

    2013-01-01

    Background Long term survival for patients with AIDS-related diffuse large B-cell lymphoma (DLBCL) is feasible in settings with available combination antiretroviral therapy (cART). However, given limited oncology resources, outcomes for AIDS-associated DLBCL in South Africa are unknown. Methods We performed a retrospective analysis of survival in patients with newly diagnosed AIDS-related diffuse large B-cell lymphoma (DLBCL) treated at a tertiary teaching hospital in Cape Town, South Africa with CHOP or CHOP-like chemotherapy (January 2004 until Dec 2010). HIV and lymphoma related prognostic factors were evaluated. Results 36 patients evaluated; median age 37.3 years, 52.8% men, and 61.1% black South Africans. Median CD4 count 184 cells/μl (in 27.8% this was < 100 cells/μl), 80% high-risk according to the age-adjusted International Prognostic Index. Concurrent Mycobacterium tuberculosis in 25%. Two-year overall survival (OS) was 40.5% (median OS 10.5 months, 95%CI 6.5 – 31.8). ECOG performance status of 2 or more (25.4% versus 50.0%, p = 0.01) and poor response to cART (18.0% versus 53.9%, p = 0.03) predicted inferior 2-year OS. No difference in 2-year OS was demonstrated in patients co-infected with Mycobacterium tuberculosis (p = 0.87). Conclusions Two-year OS for patients with AIDS-related DLBCL treated with CHOP like regimens and cART is comparable to that seen in the US and Europe. Important factors effecting OS in AIDS-related DLBCL in South Africa include performance status at presentation and response to cART. Patients with co-morbid Mycobacterium tuberculosis or hepatitis B seropositivity appear to tolerate CHOP in our setting. Additional improvements in outcomes are likely possible. PMID:23797692

  2. Immunophenotypic Analysis of AIDS-Related Diffuse Large B-Cell Lymphoma and Clinical Implications in Patients From AIDS Malignancies Consortium Clinical Trials 010 and 034

    PubMed Central

    Chadburn, Amy; Chiu, April; Lee, Jeannette Y.; Chen, Xia; Hyjek, Elizabeth; Banham, Alison H.; Noy, Ariela; Kaplan, Lawrence D.; Sparano, Joseph A.; Bhatia, Kishor; Cesarman, Ethel

    2009-01-01

    Purpose Diffuse large B-cell lymphoma (DLBCL) represents a clinically heterogeneous disease. Models based on immunohistochemistry predict clinical outcome. These include subdivision into germinal center (GC) versus non-GC subtypes; proliferation index (measured by expression of Ki-67), and expression of BCL-2, FOXP1, or B-lymphocyte-induced maturation protein (Blimp-1)/PRDM1. We sought to determine whether immunohistochemical analyses of biopsies from patients with DLBCL having HIV infection are similarly relevant for prognosis. Patients and Methods We examined 81 DLBCLs from patients with AIDS in AMC010 (cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP] v CHOP-rituximab) and AMC034 (etoposide, doxorubicin, vincristine, prednisone, and dose-adjusted cyclophosphamide plus rituximab concurrent v sequential) clinical trials and compared the immunophenotype with survival data, Epstein-Barr virus (EBV) positivity, and CD4 counts. Results The GC and non-GC subtypes of DLBCL did not differ significantly with respect to overall survival or CD4 count at cancer presentation. EBV could be found in both subtypes of DLBCL, although less frequently in the GC subtype, and did not affect survival. Expression of FOXP1, Blimp-1/PRDM1, or BCL-2 was not correlated with the outcome in patients with AIDS-related DLBCL. Conclusion These data indicate that with current treatment strategies for lymphoma and control of HIV infection, commonly used immunohistochemical markers may not be clinically relevant in HIV-infected patients with DLBCL. The only predictive immunohistochemical marker was found to be Ki-67, where a higher proliferation index was associated with better survival, suggesting a better response to therapy in patients whose tumors had higher proliferation rates. PMID:19752343

  3. Gene Therapy After Frontline Chemotherapy in Treating Patients With AIDS-Related Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-03-14

    AIDS-related Diffuse Large Cell Lymphoma; AIDS-related Diffuse Mixed Cell Lymphoma; AIDS-related Diffuse Small Cleaved Cell Lymphoma; AIDS-related Immunoblastic Large Cell Lymphoma; AIDS-related Lymphoblastic Lymphoma; AIDS-related Small Noncleaved Cell Lymphoma; HIV Infection

  4. Vorinostat and Combination Chemotherapy With Rituximab in Treating Patients With HIV-Related Diffuse Large B-Cell Non-Hodgkin Lymphoma or Other Aggressive B-Cell Lymphomas

    ClinicalTrials.gov

    2016-09-08

    AIDS-Related Diffuse Large Cell Lymphoma; AIDS-Related Plasmablastic Lymphoma; AIDS-Related Primary Effusion Lymphoma; Grade 3b Follicular Lymphoma; HIV Infection; Plasmablastic Lymphoma; Primary Effusion Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage I Grade 3 Follicular Lymphoma; Stage II Contiguous Adult Diffuse Large Cell Lymphoma; Stage II Grade 3 Contiguous Follicular Lymphoma; Stage II Grade 3 Non-Contiguous Follicular Lymphoma; Stage II Non-Contiguous Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Grade 3 Follicular Lymphoma

  5. General Information about AIDS-Related Lymphoma

    MedlinePlus

    ... AIDS-Related Lymphoma Treatment (PDQ®)–Patient Version General Information About AIDS-Related Lymphoma Go to Health Professional ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  6. Large molecules in diffuse interstellar clouds

    SciTech Connect

    Lepp, S.; Dalgarno, A.; Van Dishoeck, E.F.; Black, J.H.

    1988-06-01

    The effects of the presence of a substantial component of large molecules on the chemistry of diffuse molecular clouds are explored, and detailed models of the zeta Persei and zeta Ophiuchi clouds are constructed. The major consequence is a reduction in the abundances of singly charged atomic species. The long-standing discrepancy between cloud densities inferred from rotational and fine-structure level populations and from the ionization balance can be resolved by postulating a fractional abundance of large molecules of 1 x 10 to the -7th for zeta Persei and 6 x 10 to the -7th for zeta Ophiuchi. If the large molecules are polycyclic aromatic hydrocarbons (PAH) containing about 50 carbon atoms, they contain 1 percent of the carbon in zeta Persei and 7 percent in zeta Ophiuchi. Other consequences of the possible presence of PAH molecules are discussed. 23 references.

  7. Direct Measurement of Large, Diffuse, Optical Structures

    NASA Technical Reports Server (NTRS)

    Saif, Babak N.; Keski-Kuha, Ritva; Feinberg, Lee; Wyant, J. C.; Atkinson, C.

    2004-01-01

    Digital Speckle Pattern Interferometry (DSPI) is a well-established method for the measurement of diffuse objects in experimental mechanics. DSPIs are phase shifting interferometers. Three or four bucket temporal phase shifting algorithms are commonly used to provide phase shifting. These algorithms are sensitive to vibrations and can not be used to measure large optical structures far away from the interferometer. In this research a simultaneous phase shifted interferometer, PhaseCam product of 4D Technology Corporation in Tucson Arizona, is modified to be a Simultaneous phase shifted Digital Speckle Pattern Interferometer (SDSPI). Repeatability, dynamic range, and accuracy of the SDSPI are characterized by measuring a 5 cm x 5 cm carbon fiber coupon.

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

    ClinicalTrials.gov

    2016-05-10

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

  9. NHL (diffuse large B-cell lymphoma)

    PubMed Central

    2010-01-01

    Introduction Non-Hodgkin’s lymphoma (NHL) is the sixth most common cancer in the UK; 9443 new cases were diagnosed in the UK in 2002, and it caused 4418 UK deaths in 2003. Incidence rates show distinct geographical variation, with age-standardised incidence rates ranging from 17 per 100,000 in northern America to 4 per 100,000 in south-central Asia. NHL occurs more commonly in males than in females, and the age-standardised UK incidence increased by 10.3% between 1993 and 2002. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of first-line treatments for aggressive, or for relapsed aggressive, non-Hodgkin's lymphoma (diffuse large B-cell lymphoma)? We searched: Medline, Embase, The Cochrane Library, and other important databases up to January 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 26 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: allogeneic stem-cell support, chemotherapy (conventional dose salvage, high-dose plus autologous transplant stem-cell support, conventional dose in people with chemosensitive disease), CHOP 14, CHOP 21, CHOP 21 with radiotherapy, CHOP 21 with rituximab, ACVBP, MACOP-B, m-BACOD, PACEBOM, and ProMACE-CytaBOM. PMID:21406125

  10. Aids-Related Cancers in Africa

    NASA Astrophysics Data System (ADS)

    Mbulaiteye, Sam M.

    2014-07-01

    Thank you Professor Zichichi for inviting me to give a talk about AIDS-related cancers in Africa. Let me begin by congratulating the team that organized the 46th Session of the Erice International Seminar Series, whose theme is THE ROLE OF SCIENCE IN THE THIRD MILLENIUM. I also congratulate the scientists from 38 countries who are attending these seminars. They are perpetuating the principle of SCIENCE WITHOUT SECRETS in the true spirit espoused by Archimedes, Galileo, and Fermi. It is a wonderful honor for me to be here to shed some light on the health impacts of the HIV epidemic in the area of cancer...

  11. Thymostimulin treatment in AIDS-related complex.

    PubMed

    Palmisano, L; Chisesi, T; Galli, M; Gritti, F M; Ielasi, G; Lazzarin, A; Mezzaroma, I; Moroni, M; Raise, E; Vaglia, A

    1988-06-01

    Thirty-four patients with AIDS-related complex (ARC) were treated for 6 months with thymostimulin, a thymic hormone. Clinical and immunological findings after a 1-year follow-up were compared with those in 24 age- and sex-matched controls receiving no immunotherapy. Statistical evaluation after 6 and 12 months showed significant differences in the two groups. The thymostimulin-treated group had higher leukocyte and lymphocyte counts, more positivity in intradermal tests with multiple recall antigens, and less lymphadenopathy and weight loss. The number of OKT3+ and OKT4+ lymphocytes decreased significantly in the control group, but did not change in the thymostimulin-treated patients. Finally, after 18 months of follow-up, no progression to AIDS was seen among the treated subjects, whereas 3 of the controls developed the disease. We conclude that thymostimulin, alone or in combination with antiviral drugs, may be helpful in the management of ARC patients. PMID:3259480

  12. Primary Diffuse Large B-cell Lymphoma involving the Mandible.

    PubMed

    Alshahrani, Faleh Ali A; Aljabab, Abdulsalam S; Motabi, Ibraheem Hm; Alrashed, Abdullah; Anil, Sukumaran

    2015-10-01

    Lymphomas of the oral cavity are rare and typically present as intraosseous lesions that are most commonly diffuse large B-cell type. Diffuse large B-cell lymphoma (DLBCL) is an aggressive B-cell lymphoma histologically characterized by diffuse proliferation of large neoplastic B-lymphoid cells with a nuclear size equal to or exceeding normal histiocytic nuclei. A case of DLBCL of the mandible in an 18 years old male patient is presented. This report discusses this rare malignancy, including clinical presentation, histopathologic features, immunologic profile, treatment and prognosis. Though lymphoma of mandible is rare, it must be considered in differential diagnosis of swellings arising in the region. PMID:26581467

  13. Derivation of anisotropic diffusion coefficients in a large annular cavity

    SciTech Connect

    Eiichi Suetomi; Hiroshi Sekimoto )

    1993-06-01

    A small reactor for a spacecraft or a small liquid-metal reactor for urban siting, decentralized electrical units, or seawater desalination is designed for a large leakage of neutrons from the reactor core. In these reactors, a movable annular reflector is used for reactivity control. Therefore, a large annular cavity exists between the core and the shielding materials. In this paper, anisotropic diffusion coefficients for a large annular cavity are derived by equating the neutron currents obtained by the diffusion equation and by the transport equation. These diffusion coefficients depend only on the geometrical configuration of the cavity. A numerical comparison of diffusion calculations using these diffusion coefficients and transport calculations shows good agreement.

  14. Pancreatic abnormalities and AIDS related sclerosing cholangitis.

    PubMed Central

    Teare, J P; Daly, C A; Rodgers, C; Padley, S P; Coker, R J; Main, J; Harris, J R; Scullion, D; Bray, G P; Summerfield, J A

    1997-01-01

    OBJECTIVES: Biliary tract abnormalities are well recognised in AIDS, most frequently related to opportunistic infection with Cryptosporidium, Microsporidium, and cytomegalovirus. We noted a high frequency of pancreatic abnormalities associated with biliary tract disease. To define these further we reviewed the clinical and radiological features in these patients. METHODS: Notes and radiographs were available from two centres for 83 HIV positive patients who had undergone endoscopic retrograde cholangiopancreatography for the investigation of cholestatic liver function tests or abdominal pain. RESULTS: 56 patients had AIDS related sclerosing cholangitis (ARSC); 86% of these patients had epigastric or right upper quadrant pain and 52% had hepatomegaly. Of the patients with ARSC, 10 had papillary stenosis alone, 11 had intra- and extrahepatic sclerosing cholangitis alone, and 35 had a combination of the two. Ampullary biopsies performed in 24 patients confirmed an opportunistic infection in 16. In 15 patients, intraluminal polyps were noted on the cholangiogram. Pancreatograms were available in 34 of the 45 patients with papillary stenosis, in which 29 (81%) had associated pancreatic duct dilatation, often with associated features of chronic pancreatitis. In the remaining 27 patients, final diagnoses included drug induced liver disease, acalculous cholecystitis, gall bladder empyema, chronic B virus hepatitis, and alcoholic liver disease. CONCLUSION: Pancreatic abnormalities are commonly seen with ARSC and may be responsible for some of the pain not relieved by biliary sphincterotomy. The most frequent radiographic biliary abnormality is papillary stenosis combined with ductal sclerosis. Images PMID:9389948

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

    PubMed

    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

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

    NASA Astrophysics Data System (ADS)

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

    2013-08-01

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

  17. Large Scale Diffuse X-ray Emission from Abell 3571

    NASA Technical Reports Server (NTRS)

    Molnar, Sandor M.; White, Nicholas E. (Technical Monitor)

    2001-01-01

    Observations of the Luman alpha forest suggest that there are many more baryons at high redshift than we can find in the Universe nearby. The largest known concentration of baryons in the nearby Universe is the Shapley supercluster. We scanned the Shapley supercluster to search for large scale diffuse emission with the Rossi X-ray Timing Explorer (RXTE), and found some evidence for such emission. Large scale diffuse emission may be associated to the supercluster, or the clusters of galaxies within the supercluster. In this paper we present results of scans near Abell 3571. We found that the sum of a cooling flow and an isothermal beta model adequately describes the X-ray emission from the cluster. Our results suggest that diffuse emission from A3571 extends out to about two virial radii. We briefly discuss the importance of the determination of the cut off radius of the beta model.

  18. Implicit solution of large-scale radiation diffusion problems

    SciTech Connect

    Brown, P N; Graziani, F; Otero, I; Woodward, C S

    2001-01-04

    In this paper, we present an efficient solution approach for fully implicit, large-scale, nonlinear radiation diffusion problems. The fully implicit approach is compared to a semi-implicit solution method. Accuracy and efficiency are shown to be better for the fully implicit method on both one- and three-dimensional problems with tabular opacities taken from the LEOS opacity library.

  19. FAR-ULTRAVIOLET DIFFUSE EMISSION FROM THE LARGE MAGELLANIC CLOUD

    SciTech Connect

    Pradhan, Ananta C.; Pathak, Amit; Murthy, Jayant

    2010-08-01

    We present the first observations of diffuse radiation in the far-ultraviolet (FUV; 1000-1150 A) from the Large Magellanic Cloud based on observations made with the Far Ultraviolet Spectroscopic Explorer. The fraction of the total radiation in the field emitted as diffuse radiation is typically 5%-20% with a high of 45% near N70 where there are few exciting stars, indicating that much of the emission is not due to nearby stars. Much less light is scattered in the FUV than at longer wavelengths, with the stellar radiation going into heating the interstellar dust.

  20. Extracting spatial information from large aperture exposures of diffuse sources

    NASA Technical Reports Server (NTRS)

    Clarke, J. T.; Moos, H. W.

    1981-01-01

    The spatial properties of large aperture exposures of diffuse emission can be used both to investigate spatial variations in the emission and to filter out camera noise in exposures of weak emission sources. Spatial imaging can be accomplished both parallel and perpendicular to dispersion with a resolution of 5-6 arc sec, and a narrow median filter running perpendicular to dispersion across a diffuse image selectively filters out point source features, such as reseaux marks and fast particle hits. Spatial information derived from observations of solar system objects is presented.

  1. Diffuse large B cell lymphoma with chronic granulomatous inflammation.

    PubMed

    Nyunt, W W T; Wong, Y P; Wan Jamaludin, W F; Abdul Wahid, S F S

    2016-04-01

    Non-necrotic epithelioid granulomas have been reported in association with neoplasms including Hodgkin and non-Hodgkin lymphoma. We report a case of diffuse large B cell lymphoma with chronic granulomatous inflammation to highlight awareness of obscure tumour cells within the granuloma, to avoid delay in diagnosis and management of lymphoma. A 39-year-old Malay lady with no past medical history, presented with a 2-month history of progressive worsening of difficulty in breathing, cough, low-grade fever, loss of weight and loss of appetite. Chest X-ray showed an anterior mediastinal mass and computed tomography (CT)-guided biopsy was reported as chronic granulomatous inflammation suggestive of tuberculosis. After 2 months of anti-TB treatment, her symptoms were not relieved. The patient underwent another CT-guided biopsy of the anterior mediastinal mass in another hospital and the histopathology revealed diffuse large B cell lymphoma. The patient was referred for treatment. On histopathological review, the first sample showed noncaseating granulomas engulfing tumour cells and large abnormal lymphoid cells which were CD20 positive and with high Ki-67 proliferative index. The patient was diagnosed with diffuse large B cell lymphoma stage IV B IPSS score 3. She underwent chemotherapy (R-EPOCH) and responded well to treatment. PMID:27126666

  2. Combination Chemo, Rituximab, and Bevacizumab in Older Patients With Stage II-IV Diffuse Large B-Cell Lymphoma

    ClinicalTrials.gov

    2014-05-06

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

  3. Large-scale diffusion of entangled polymers along nanochannels

    NASA Astrophysics Data System (ADS)

    Saalwachter, Kay; Lange, Frank; Steinhart, Martin; Judeinstein, Patrick

    2015-03-01

    Confinement-induced changes in polymer mobility are still under active discussion. For weakly interacting poly(butadiene) chains in 100 μm long, 20 and 60 nm wide channels in anodic Al2O3, we here report on the study of the large-scale pore-averaged self diffusion on a μm scale by 1H pulsed-gradient NMR. We find weak indications of an acceleration due to surface-induced disentanglement. Unlike previous reports on polymer diffusion into particle nanocomposites of similar confinement scale, or start-up diffusivities out of even thinner films, we find an MW and temperature independent reduction of diffusivity that is solely determined by the confinement size. We rationalize this trend by a simple volume-average model, which suggests a 20-fold surface-enhanced monomeric friction on the scale of the packing length, which can be compared to a factor of 300 that our model predicts for comparable thin-film data of poly(styrene) on silica.

  4. Expression of immunohistochemical markers in patients with AIDS-related lymphoma.

    PubMed

    Barreto, Luciana; Azambuja, Denize; Morais, José Carlos de

    2012-01-01

    AIDS-related lymphomas (ARL) present high biological heterogeneity. For better characterization of this type of lymphoma, the objectives of the present study were to evaluate the expression of immunohistochemical markers of cell differentiation (CD10, Bcl-6, MUM-1) and determine cell origin profile according to Hans' classification of diffuse large B-cell lymphoma in AIDS patients. This study included 72 consecutive patients with ARL diagnosed at the University Hospital, Universidade Federal do Rio de Janeiro (UFRJ) and at the Brazilian Instituto Nacional de Câncer (INCA) from 2000 to 2006. The morphologic distribution of the lymphomas was the following: 61% were diffuse large B-cell lymphomas (DLBCLs), 15% were Burkitt's lymphomas, 13% were plasmablastic lymphomas, 10% were high-grade lymphomas and 1% was follicular lymphoma. The positivity for each immunohistochemical marker in DLBCLs, Burkitt's lymphoma and plasmablastic lymphoma was respectively: CD20, 84%, 100%, and 0; CD10, 55%, 100%, and 0; Bcl-6, 45%, 80%, and 0; MUM-1, 41%, 20%, and 88%. A higher positivity of CD20 (84% x 56%, p = 0.01) was found in DLBCL compared to non-DLBCL; in Burkitt's lymphomas a higher positivity of CD10 (100% x 49%, p = 0.04) and Bcl-6 (80% x 39%, p = 0.035) were found compared to non-Burkitt's lymphomas. Germinal center (GC) profile was detected in 60% of DLBCLs. Our study suggests particular findings in ARL, as the most frequent phenotype was GC, different from HIV-negative patients. PMID:22358360

  5. The Uneven Diffusion of Collaborative Technology in a Large Organization

    NASA Astrophysics Data System (ADS)

    Jarulaitis, Gasparas

    This paper investigates the large-scale diffusion of a collaborative technology in a range of different business contexts. The empirical data used in the article were obtained from a longitudinal (2007-2009) case study of a global oil and gas company (OGC). Our study reports on ongoing efforts to deploy an inte grated collaborative system that uses Microsoft SharePoint (MSP) technology. We assess MSP as a configurational technology and analyze the diffusion of a metadata standard developed in-house, which forms an embedded component of MSP. We focus on two different organizational contexts, namely research and development (R&D) and oil and gas production (OGP), and illustrate the key differences between the ways in which configurational technology is managed and used in these contexts, which results in an uneven diffusion. In contrast with previous studies, we unravel the organizational and technological complexity involved, and thus empirically illustrate the flexibility of large-scale technology and show how the trajectories of the various components are influenced by multiple modes of ordering.

  6. Endoscopic appearance of AIDS-related gastrointestinal lymphoma with c-MYC rearrangements: Case report and literature review

    PubMed Central

    Tanaka, Shohei; Nagata, Naoyoshi; Mine, Sohtaro; Igari, Toru; Kobayashi, Taiichiro; Sugihara, Jun; Honda, Haruhito; Teruya, Katsuji; Kikuchi, Yoshimi; Oka, Shinichi; Uemura, Naomi

    2013-01-01

    Acquired immune deficiency syndrome (AIDS)-related lymphoma (ARL) remains the main cause of AIDS-related deaths in the highly active anti-retroviral therapy (HAART) era. Recently, rearrangement of MYC is associated with poor prognosis in patients with diffuse large B-cell lymphoma. Here, we report a rare case of gastrointestinal (GI)-ARL with MYC rearrangements and coinfected with Epstein-Barr virus (EBV) infection presenting with various endoscopic findings. A 38-year-old homosexual man who presented with anemia and was diagnosed with an human immunodeficiency virus infection for the first time. GI endoscopy revealed multiple dish-like lesions, ulcerations, bloody spots, nodular masses with active bleeding in the stomach, erythematous flat lesions in the duodenum, and multiple nodular masses in the colon and rectum. Magnified endoscopy with narrow band imaging showed a honeycomb-like pattern without irregular microvessels in the dish-like lesions of the stomach. Biopsy specimens from the stomach, duodenum, colon, and rectum revealed diffuse large B-cell lymphoma concomitant with EBV infection that was detected by high tissue EBV-polymerase chain reaction levels and Epstein-Barr virus small RNAs in situ hybridization. Fluorescence in situ hybridization analysis revealed a fusion between the immunoglobulin heavy chain (IgH) and c-MYC genes, but not between the IgH and BCL2 loci. After 1-mo of treatment with HAART and R-CHOP, endoscopic appearance improved remarkably, and the histological features of the biopsy specimens revealed no evidence of lymphoma. However, he died from multiple organ failure on the 139th day after diagnosis. The cause of his poor outcome may be related to MYC rearrangement. The GI tract involvement in ARL is rarely reported, and its endoscopic findings are various and may be different from those in non-AIDS GI lymphoma; thus, we also conducted a literature review of GI-ARL cases. PMID:23922484

  7. Endoscopic appearance of AIDS-related gastrointestinal lymphoma with c-MYC rearrangements: case report and literature review.

    PubMed

    Tanaka, Shohei; Nagata, Naoyoshi; Mine, Sohtaro; Igari, Toru; Kobayashi, Taiichiro; Sugihara, Jun; Honda, Haruhito; Teruya, Katsuji; Kikuchi, Yoshimi; Oka, Shinichi; Uemura, Naomi

    2013-08-01

    Acquired immune deficiency syndrome (AIDS)-related lymphoma (ARL) remains the main cause of AIDS-related deaths in the highly active anti-retroviral therapy (HAART) era. Recently, rearrangement of MYC is associated with poor prognosis in patients with diffuse large B-cell lymphoma. Here, we report a rare case of gastrointestinal (GI)-ARL with MYC rearrangements and coinfected with Epstein-Barr virus (EBV) infection presenting with various endoscopic findings. A 38-year-old homosexual man who presented with anemia and was diagnosed with an human immunodeficiency virus infection for the first time. GI endoscopy revealed multiple dish-like lesions, ulcerations, bloody spots, nodular masses with active bleeding in the stomach, erythematous flat lesions in the duodenum, and multiple nodular masses in the colon and rectum. Magnified endoscopy with narrow band imaging showed a honeycomb-like pattern without irregular microvessels in the dish-like lesions of the stomach. Biopsy specimens from the stomach, duodenum, colon, and rectum revealed diffuse large B-cell lymphoma concomitant with EBV infection that was detected by high tissue EBV-polymerase chain reaction levels and Epstein-Barr virus small RNAs in situ hybridization. Fluorescence in situ hybridization analysis revealed a fusion between the immunoglobulin heavy chain (IgH) and c-MYC genes, but not between the IgH and BCL2 loci. After 1-mo of treatment with HAART and R-CHOP, endoscopic appearance improved remarkably, and the histological features of the biopsy specimens revealed no evidence of lymphoma. However, he died from multiple organ failure on the 139(th) day after diagnosis. The cause of his poor outcome may be related to MYC rearrangement. The GI tract involvement in ARL is rarely reported, and its endoscopic findings are various and may be different from those in non-AIDS GI lymphoma; thus, we also conducted a literature review of GI-ARL cases. PMID:23922484

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

    ClinicalTrials.gov

    2016-08-01

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

  9. Diffuse large B-cell lymphoma of the prostate.

    PubMed

    Warrick, Joshua I; Owens, Scott R; Tomlins, Scott A

    2014-10-01

    In this article, we review prostatic lymphomas and discuss the differential diagnosis of high-grade malignant neoplasms of the prostate. We illustrate this with a case of a 46-year-old man seen with lower urinary tract obstruction who had diffuse involvement by a high-grade malignancy on prostate biopsy. Morphologic evaluation and immunohistochemistry were consistent with diffuse large B-cell lymphoma of the prostate. Workup with positron emission tomography-computed tomography demonstrated intensely hypermetabolic lymph nodes in the mediastinum, as well as widespread osseous involvement and involvement of the pancreatic tail, prostate, and urinary bladder, suggesting secondary prostatic involvement by a nodal lymphoma. Lymphomas of the prostate are uncommon in surgical pathology practice and usually represent secondary involvement from leukemia/lymphoma at a more typical site. Chronic lymphocytic leukemia/small lymphocytic lymphoma is the most common subtype. PMID:25268190

  10. AIDS-related apprehensions among nursing students of Delhi.

    PubMed

    Kumar, A; Lal, P; Ingle, G K; Gulati, N

    1999-12-01

    Students from a nursing school of Delhi were surveyed anonymously using a self-administered questionnaire to explore various AIDS-related apprehensions and their possible reasons. The observations revealed that, majority of the students and their families/friends feared that these students were at risk of contracting HIV infection while providing routine patient care. A large number of students also opined that they would feel uncomfortable while talking, hugging, shaking hands, and sharing a room with an HIV positive person. The main reasons for their apprehensions were unsatisfactory anti-AIDS campaigning by the government, non-availability of sufficient protective measures in the health care settings, inadequate professional education related to prevention of HIV infection, and increase in HIV transmission following false sense of security due to excessive condom promotion. Findings of the study imply imparting factual knowledge addressing the concerns and removing misconceptions which influence attitudes and willingness of the nursing students to provide care to the HIV positives/AIDS patients, facts regarding efficacy of various preventive measures, and provision of counselling services in the event of exposure. PMID:10937297

  11. The tumor virus landscape of AIDS-related lymphomas.

    PubMed

    Arvey, Aaron; Ojesina, Akinyemi I; Pedamallu, Chandra Sekhar; Ballon, Gianna; Jung, Joonil; Duke, Fujiko; Leoncini, Lorenzo; De Falco, Giulia; Bressman, Eric; Tam, Wayne; Chadburn, Amy; Meyerson, Matthew; Cesarman, Ethel

    2015-05-14

    Immunodeficiency dramatically increases susceptibility to cancer as a result of reduced immune surveillance and enhanced opportunities for virus-mediated oncogenesis. Although AIDS-related lymphomas (ARLs) are frequently associated with known oncogenic viruses, many cases contain no known transforming virus. To discover novel transforming viruses, we profiled a set of ARL samples using whole transcriptome sequencing. We determined that Epstein-Barr virus (EBV) was the only virus detected in the tumor samples of this cohort, suggesting that if unidentified pathogens exist in this disease, they are present in <10% of cases or undetectable by our methods. To evaluate the role of EBV in ARL pathogenesis, we analyzed viral gene expression and found highly heterogeneous patterns of viral transcription across samples. We also found significant heterogeneity of viral antigen expression across a large cohort, with many patient samples presenting with restricted type I viral latency, indicating that EBV latency proteins are under increased immunosurveillance in the post-combined antiretroviral therapies era. Furthermore, EBV infection of lymphoma cells in HIV-positive individuals was associated with a distinct host gene expression program. These findings provide insight into the joint host-virus regulatory network of primary ARL tumor samples and expand our understanding of virus-associated oncogenesis. Our findings may also have therapeutic implications, as treatment may be personalized to target specific viral and virus-associated host processes that are only present in a subset of patients. PMID:25827832

  12. SCIMAP: Modelling Diffuse Pollution in Large River Basins

    NASA Astrophysics Data System (ADS)

    Milledge, D.; Heathwaite, L.; Lane, S. N.; Reaney, S. M.

    2009-12-01

    Polluted rivers are a problem for the plants and animals that require clean water to survive. Watershed scale processes can influence instream aquatic ecosystems by delivering fine sediment, solutes and organic matter from diffuse sources. To improve our rivers we need to identify the pollution sources. Models can help us to do this but these rarely address the extent to which risky land uses are hydrologically-connected, and hence able to deliver, to the drainage network. Those that do tend to apply a full hydrological scheme, which is unfeasible for large watersheds. Here we develop a risk-based modelling framework, SCIMAP, for diffuse pollution from agriculture (Nitrate, Phosphate and Fine Sediment). In each case the basis of the analysis is the joint consideration of the probability of a unit of land (25 m2 cell) producing a particular environmental risk and then of that risk reaching the river. The components share a common treatment of hydrological connectivity but differ in their treatment of each pollution type. We test and apply SCIMAP using spatially-distributed instream water quality data for some of the UK’s largest catchments to infer the processes and the associated process parameters that matter in defining their concentrations. We use these to identify a series of risky field locations, where this land use is readily connected to the river system by overland flow.

  13. Large Eddy Simulation of a Sooting Jet Diffusion Flame

    NASA Astrophysics Data System (ADS)

    Blanquart, Guillaume; Pitsch, Heinz

    2007-11-01

    The understanding of soot particle dynamics in combustion systems is a key issue in the development of low emission engines. Of particular importance are the processes shaping the soot particle size distribution function (PSDF). However, it is not always necessary to represent exactly the full distribution, and often information about its moments only is sufficient. The Direct Quadrature Method of Moments (DQMOM) allows for an efficient and accurate prediction of the moments of the soot PSDF. This method has been validated for laminar premixed and diffusion flames with detailed chemistry and is now implemented in a semi-implicit low Mach-number Navier-Stokes solver. A Large Eddy Simulation (LES) of a piloted sooting jet diffusion flame (Delft flame) is performed to study the dynamics of soot particles in a turbulent environment. The profiles of temperature and major species are compared with the experimental measurements. Soot volume fraction profiles are compared with the recent data of Qamar et al. (2007). Aggregate properties such as the diameter and the fractal shape are studied in the scope of DQMOM.

  14. Psychological Consequences of AIDS-Related Bereavement among Gay Men.

    ERIC Educational Resources Information Center

    Martin, John L.

    1988-01-01

    Interviewed 745 homosexual men to examine relation between Acquired Immune Deficiency Syndrome (AIDS)-related bereavement and psychological distress. Loss of lover or close friend to AIDS was reported by 27 percent of sample. Found direct relation between number of bereavements and symptoms of traumatic stress response, demoralization, sleep…

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

    PubMed

    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. PMID:19496708

  16. Small and Large Molecules in the Diffuse Interstellar Medium

    NASA Astrophysics Data System (ADS)

    Oka, Takeshi; Huang, Jane

    2014-06-01

    Although molecules with a wide range of sizes exist in dense clouds (e.g. H(C≡C)_nC≡N with n = 0 - 5), molecules identified in diffuse clouds are all small ones. Since the initial discovery of CH, CN, and CH^+, all molecules detected in the optical region are diatomics except for H_3^+ in the infrared and C_3 in the visible. Radio observations have been limited up to triatomic molecules except for H_2CO and the ubiquitous C_3H_2. The column densities of all molecules are less than 1014 cm-2 with the two exceptions of CO and H_3^+ as well as CH and C_2 in a few special sightlines. Larger molecules with many carbon atoms have been searched for but have not been detected. On the other hand, the observations of a great many diffuse interstellar bands (380 toward HD 204827 and 414 toward HD 183143) with equivalent widths from 1 to 5700 m Å indicate high column densities of many heavy molecules. If an electronic transition dipole moment of 1 Debye is assumed, the observed equivalent widths translate to column densities from 5 × 1011 cm-2 to 3 × 1015 cm-2. It seems impossible that these large molecules are formed from chemical reactions in space from small molecules. It is more likely that they are fragments of aggregates, perhaps mixed aromatic/aliphatic organic nanoparticles (MAONS). MAONS and their large fragment molecules are stable against photodissociation in the diffuse ISM because the energy of absorbed photons is divided into statistical distributions of vibrational energy and emitted in the infrared rather than breaking a chemical bond. We use a simple Rice-Ramsperger-Kassel-Marcus theory to estimate the molecular size required for the stabilization. Snow, T. P. & McCall, B. J. 2006, ARA&A, 44 367 Hobbs, L. M., York, D. G., Snow, T. P., Oka, T., Thorburn, J. A., et al. 2008, ApJ, 680 1256 Hobbs, L. M., York, D. G., Thorburn, J. A., Snow, T. P., Bishof, M., et al. 2009, ApJ, 705 32 Kwok, S. & Zhang, S. 2013, ApJ, 771 5 Freed, K. F., Oka, T., & Suzuki, H

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

    ClinicalTrials.gov

    2012-10-11

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

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

    ClinicalTrials.gov

    2016-03-01

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

  19. Patterns of gallium-67 scintigraphy in patients with acquired immunodeficiency syndrome and the AIDS related complex

    SciTech Connect

    Bitran, J.; Bekerman, C.; Weinstein, R.; Bennett, C.; Ryo, U.; Pinsky, S.

    1987-07-01

    Thirty-two patients with AIDS related complex (ARC) or acquired immunodeficiency syndrome (AIDS) underwent /sup 67/Ga scans as part of their evaluation. Three patterns of /sup 67/Ga biodistribution were found: lymph node uptake alone; diffuse pulmonary uptake; normal scan. Gallium-67 scans were useful in identifying clinically occult Pneumocystis carinii pneumonia in seven of 15 patients with ARC who were asymptomatic and had normal chest radiographs. Gallium scans are a useful ancillary procedure in the evaluation of patients with ARC or AIDS.

  20. AT13387 in Treating Patients With Relapsed or Refractory Anaplastic Large Cell Lymphoma, Mantle Cell Lymphoma, or Diffuse Large B-cell Lymphoma

    ClinicalTrials.gov

    2016-09-01

    Anaplastic Large Cell Lymphoma, ALK-Positive; Recurrent Anaplastic Large Cell Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mantle Cell Lymphoma; Refractory Anaplastic Large Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mantle Cell Lymphoma

  1. The Histological Classification of Diffuse Large B-cell Lymphomas

    PubMed Central

    Xie, Yi; Pittaluga, Stefania; Jaffe, Elaine S.

    2015-01-01

    Diffuse large B cell lymphomas (DLBCLs) are aggressive B-cell neoplasms with considerable clinical, biologic and pathologic diversity, in part reflecting the functional diversity of the B-cell system and multiple pathways of transformation. In recent years, the advent of new high-throughput genomic technologies has provided new insights into the biology of DLBCL, leading to the identification of distinct molecular identities and novel pathogenetic pathways. This increasing complexity had led to an expanding number of entities in the WHO classification. Using a multi-modality approach, the updated 2008 classification delineated some new subgroups, including DLBCLs associated with particular age groups or specific anatomic sites, as well as two borderline categories: tumors at the interface between classical Hodgkin lymphoma (cHL) and DLBCL as well as between Burkitt Lymphoma (BL) and DLBCL. This article reviews the histopathologic features of the various aggressive B-cell lymphoma subtypes included in the 2008 classification, with emphasis on some of the new entities as well as areas of diagnostic challenge. PMID:25805585

  2. MicroRNAs in diffuse large B-cell lymphoma

    PubMed Central

    NI, HUIYUN; TONG, RONG; ZOU, LINQING; SONG, GUOQI; CHO, WILLIAM C.

    2016-01-01

    The aberrant expression of microRNAs (miRs) has a significant impact on the biological characteristics of lymphocytes, and is important in the pathogenesis of diffuse large B-cell lymphoma (DLBCL). It has been demonstrated, using miR profiling and detecting distinct miR signatures, that certain miRs may accurately distinguish different subtypes and prognostic classifications of DLBCL, as well as distinguish DLBCL from other more indolent lymphomas, including follicular lymphoma. miRs are excellent biomarkers for cancer diagnosis and prognosis. In DLBCL, specific miR expression profiles in the tissues of patients are associated with prognosis and clinical outcome. Over the past decade, there has been substantial investigation concerning the pathogenetic, diagnostic and prognostic roles of miRs in DLBCL. The aim of the present review is to describe the aberrant expression of miRs in DLBCL, and the functions, potential clinical use and possible therapeutic targets of miRs in this disease. PMID:26893730

  3. The Genetic Landscape of Diffuse Large B Cell Lymphoma

    PubMed Central

    Pasqualucci, Laura; Dalla-Favera, Riccardo

    2015-01-01

    Diffuse large B cell lymphoma (DLBCL), the most common lymphoid malignancy in the western world, is an aggressive disease that remains incurable in approximately 30% of patients. Over the past decade, the rapid expansion of sequencing technologies allowing the genome-wide assessment of genomic and transcriptional changes has revolutionized our understanding of the genetic basis of DLBCL by providing a comprehensive and unbiased view of the genes/pathways that are disrupted by genetic alterations in this disease, and may contribute to tumor initiation and expansion. These studies uncovered the existence of several previously unappreciated alterations in key cellular pathways that may also influence treatment outcome. Indeed, a number of newly identified genetic lesions are currently being explored as markers for improved diagnosis and risk stratification, or are entering clinical trials as promising therapeutic targets. This review focuses on recent advances in the genomic characterization of DLBCL and discusses how information gained from these efforts has provided new insights into its biology, uncovering potential targets of prognostic and therapeutic relevance. PMID:25805586

  4. Diffuse large B-cell lymphoma: A metabolic disorder?

    PubMed Central

    Tanios, Georges; Aranguren, Ines M.; Goldstein, Jack S.; Patel, Chirag B.

    2013-01-01

    Patient Male, 81 Final Diagnosis: Non-Hodgkin lymphoma Symptoms: General weakness • hypoglycemia • metabolic acidosis Medication: — Clinical Procedure: — Specialty: Hematology Objective: Challenging differential diagnosis Background: B cell lymphoma constitutes 80–85% of cases of Non Hodgkin’s lymphoma in the Untied States. Metabolic complications may arise from the disease itself or through its end organ involvement. Case Report: We describe a case of a diffuse large B cell lymphoma diagnosed by abdominal computed tomography after it initially presented as hypoglycemia not correctable by dextrose infusion that instead resulted in increased anion gap metabolic acidosis with elevated lactate levels. Conclusions: The case illustrates how lymphomas can present unusually with hypoglycemia and lactic acidosis, the latter being an ominous sign that can occur without liver involvement. In this regard, the case demonstrates the metabolic sequelae of lymphoma that should raise suspicion for an underlying process. This has implications for diagnosis, treatment, and patient survival. Attention should be paid especially in the primary care setting in order to minimize delays in diagnosis. PMID:24349605

  5. Large-scale dynamics of sandy coastlines: Diffusivity and instability

    NASA Astrophysics Data System (ADS)

    FalquéS, A.; Calvete, D.

    2005-03-01

    The dynamics of small-amplitude perturbations of an otherwise rectilinear coastline due to the wave-driven alongshore sediment transport is examined at large time and length scales (years and kilometers). A linear stability analysis is performed by using an extended one-line shoreline model with two main improvements: (1) the curvature of the coastline features is accounted for and (2) the coastline features are assumed to extend offshore as a bathymetric perturbation up to a finite distance. For high incidence angles, instability is found in accordance with Ashton et al. (2001). However, it is seen that instability is inhibited by high waves with long periods and gently sloping shorefaces so that in this case the coastline may be stable for any angle. Similarly, there is no instability if the bathymetric perturbation is confined very close to the coast. It is found that the traditional linearized one-line model (Larson et al., 1987) tends to overpredict the coastline diffusivity. The overprediction is small for the conditions leading to a stable coastline and for moderate incidence angles but can be very dramatic for the conditions favoring instability. An interesting finding is that high-angle waves instability has a dominant wavelength at the linear regime, which is in the order of 4-15 km, one to two orders of magnitude larger than the length scale of surf zone rhythmic features. Intriguingly, this is roughly the same range of the wavelength of some observed shoreline sand waves and, in particular, those observed along the Dutch coast. A model application to this coast is presented.

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

    PubMed Central

    Savsek, Lina; Opaskar, Tanja Ros

    2016-01-01

    Background 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. Case report 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, 8th 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. Conclusions 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. PMID

  7. Angiomirs expression profiling in diffuse large B-Cell lymphoma

    PubMed Central

    Borges, Natália M.; do Vale Elias, Marcela; Fook-Alves, Veruska L.; Andrade, Tathiana A.; de Conti, Marina Lourenço; Macedo, Mariana Petaccia; Begnami, Maria Dirlei; Campos, Antônio Hugo J. F. M.; Etto, Leina Yukari; Bortoluzzo, Adriana Bruscato; Alves, Antonio C.; Young, Ken H.; Colleoni, Gisele W. B.

    2016-01-01

    Despite advances in treatment, 30% of diffuse large B-cell lymphoma (DLBCL) cases are refractory or relapse after chemoimmunotherapy. Currently, the relationship between angiogenesis and angiomiRs in DLBCL is unknown. We classified 84 DLBCL cases according to stromal signatures and evaluated the expression of pro- and antiangiomiRs in paraffin embedded tissues of DLBCL and correlated them with microvascular density (MVD). 40% of cases were classified as stromal-1, 50% as stromal-2 and 10% were not classified. We observed increased expression of proangiomiRs Let-7f, miR-17, miR-18a, miR-19b, miR-126, miR-130a, miR-210, miR-296 and miR-378 in 14%, 57%, 30%, 45%, 12%, 12%, 56%, 58% and 48% of the cases, respectively. Among antiangiomiRs we found decreased expression of miR-16, miR-20b, miR-92a, miR-221 and miR-328 in, respectively, 27%, 71%, 2%, 44% and 11%. We found association between increased expression of proangiomiRs miR-126 and miR-130a and antiangiomiR miR-328 and the subtype non-GCB. We found higher levels of the antiangiomiRs miR-16, miR-221 and miR-328 in patients with low MVD and stromal-1 signature. IPI and CD34 confirmed independent impact on survival of the study group. None of the above angiomiRs showed significance as biomarker in an independent serum samples cohort of patients and controls. In conclusion, we confirmed association between antiangiomiRs miR-16, miR-221 and miR-328 and stromal-1 signature. Four angiomiRs emerged as potential therapeutic targets: proangiomiRs miR-17, miR-210 and miR-296 and antiangiomiR miR-20b. Although the four microRNAs seem to be important in DLBCL pathogenesis, they were not predictive of DLBCL onset or relapse in the serum independent cohort. PMID:26683099

  8. HIV/AIDS-related stigma in Kumasi, Ghana

    PubMed Central

    Ulasi, Chijioke I; Preko, Peter O; Baidoo, Joseph A.; Bayard, Budry; Ehiri, John E; Jolly, Curtis M; Jolly, Pauline E

    2009-01-01

    Objective To assess HIV/AIDS-related stigma and discrimination of people living with HIV/AIDS (PLWHA) in Kumasi, Ghana. Methods A cross-sectional survey of 104 adults from the four sub-districts in Kumasi was conducted. Results Four stigma constructs, employment-based discrimination, screening and identification of HIV positive people, revelation of HIV status and social contact stigma were determined based on reliability measures from responses to the questionnaire. Regression analysis showed that participants with higher educational attainment were more likely to favor policies denying employment to PLWHA (p<0.05), but disapproved of revealing HIV sero-status (p<0.05). Muslims were more likely than Christians to agree with identifying PLWHA (p<0.05) and more likely to advocate revealing HIV sero-status (p<0.05). Males were more likely to favor revealing HIV status (p<0.05). Employed persons were more likely to have social contact with PLWHA (p<0.05). Conclusions These findings are useful in guiding the design of interventions against HIV/AIDS-related stigma in Kumasi. PMID:18632302

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

    ClinicalTrials.gov

    2016-09-13

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

  10. An homeopathic cure to pure Xenon large diffusion

    NASA Astrophysics Data System (ADS)

    Azevedo, C. D. R.; Fernandes, L. M. P.; 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.

    2016-02-01

    The NEXT neutrinoless double beta decay (ββ0ν) 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 Qββ. The rejection potential associated to the topology reconstruction is limited by our capacity to properly 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 some important parameters like diffusion, drift velocity and light yields. These results show that there is a series of candidates that can reduce diffusion without affecting the energy resolution of the detector and they should be studied experimentally. A comparison with preliminary results from such an ongoing experimental effort is given.

  11. The Diffuse Ionized Gas in the large telescopes era

    NASA Astrophysics Data System (ADS)

    Hidalgo-Gámez, A. M.

    2005-12-01

    In this workshop we summarize the ``state of the art'' of the Diffuse Ionized Gas. We present all the possible situations which can produce ionization outside an H II region, as well as some of the observations that can be performed with the GTC instrumentation and how relevant they can be in the undestanding of the ionization mechanisms of the DIG.

  12. Photodynamic therapy for treatment of AIDS-related mucocutaneous Kaposi's sarcoma (Invited Paper)

    NASA Astrophysics Data System (ADS)

    Schweitzer, Vanessa G.

    1992-06-01

    Since 1975, Phase I/II studies have demonstrated the successfulness of hematoporphyrin derivative photodynamic therapy (PDT) in the treatment of various malignancies of the skin, eye, bladder, lung, and head and neck. Moreover, in 1981 two cases of traditional Western cutaneous Kaposi's sarcoma (TKS) have been treated with photodynamic therapy with both early and late complete response. To date, attempts to cure and palliation of the more aggressive AIDS-related oral Kaposi's sarcoma with conventional radiation, chemotherapy or immunotherapy, or surgical excision have been limited and often associated with debilitating mucositis and further immunosuppression. Certain aspects of photodynamic therapy may be efficacious for treatment of mucocutaneous Kaposi's sarcoma: (1) the selective retention of hematoporphyrin derivative by neoplastic lesions (endothelial cell tumors); (2) a tumor- specific cytotoxic agent (i.e., free oxygen radical); (3) absence of systemic toxicity from immunosuppression; (4) the potential for retreatment without increasing side effects; and (5) porphyrin-mediated photoinactivation of enveloped viruses. Herein presented are seven cases of AIDS-related KS (EKS) with diffuse, superficial, and nodular mucocutaneous lesions treated with dihematoporphyrin derivative and photodynamic therapy with subsequent dramatic early partial and complete responses.

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

    ClinicalTrials.gov

    2016-06-20

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

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

    ClinicalTrials.gov

    2013-01-04

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

  15. Successful treatment with autologous peripheral blood stem cell transplantation for acquired immunodeficiency syndrome (AIDS)-related malignant lymphoma.

    PubMed

    NAGAI, Yuya; MORI, Minako; INOUE, Daichi; KIMURA, Takaharu; SHIMOJI, Sonoko; TOGAMI, Katsuhiro; TABATA, Sumie; MATSUSHITA, Akiko; NAGAI, Kenichi; Imai, Yukihiro; Takafuta, Toshiro; Takahashi, Takayuki

    2009-11-01

    A 62-year-old man was diagnosed with human immunodeficiency virus (HIV) infection while suffering from recurrent herpes zoster infection. Laboratory examination revealed CD4(+) lymphocyte count 16 cells/mul and HIV loading 150,000 copies/ml at presentation. In addition, he had multiple lymph node swelling. Histologic diagnosis of a biopsied lymph node was diffuse, large, B cell-type malignant lymphoma. The karyotype of the lymphoma cells was t(8;14)(q24;q32), which was confirmed by G-banding and fluorescent in situ hybridization. Positron emission tomography (PET)-combined CT scanning revealed systemic extranodal tumors involving the gastrointestinal tract, pancreas, and bone marrow. The clinical stage of the lymphoma was IVB and the international prognosis index was categorized as high. Complete remission (CR) of the lymphoma was obtained after 2 courses of CHOP (cyclophosphamide, adriamycin, vincristine, prednisolone) chemotherapy and 4 subsequent courses of rituximab-combined CHOP (R-CHOP). Highly active antiretroviral therapy (HAART) was started at the initiation of CHOP. Because of the poor prognosis of AIDS-related lymphoma, he received autologous peripheral blood stem cell transplantation with the MEAM protocol (ranimustine, etoposide, cytarabine, melphalan) as a conditioning procedure without a severe infectious episode. He remains in CR 24 months after the transplantation. PMID:20009441

  16. On Large Time Behavior and Selection Principle for a Diffusive Carr-Penrose Model

    NASA Astrophysics Data System (ADS)

    Conlon, Joseph G.; Dabkowski, Michael; Wu, Jingchen

    2016-04-01

    This paper is concerned with the study of a diffusive perturbation of the linear LSW model introduced by Carr and Penrose. A main subject of interest is to understand how the presence of diffusion acts as a selection principle, which singles out a particular self-similar solution of the linear LSW model as determining the large time behavior of the diffusive model. A selection principle is rigorously proven for a model which is a semiclassical approximation to the diffusive model. Upper bounds on the rate of coarsening are also obtained for the full diffusive model.

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

    ClinicalTrials.gov

    2016-09-07

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

  18. Locating the Source of Diffusion in Large-Scale Networks

    NASA Astrophysics Data System (ADS)

    Pinto, Pedro C.; Thiran, Patrick; Vetterli, Martin

    2012-08-01

    How can we localize the source of diffusion in a complex network? Because of the tremendous size of many real networks—such as the internet or the human social graph—it is usually unfeasible to observe the state of all nodes in a network. We show that it is fundamentally possible to estimate the location of the source from measurements collected by sparsely placed observers. We present a strategy that is optimal for arbitrary trees, achieving maximum probability of correct localization. We describe efficient implementations with complexity O(Nα), where α=1 for arbitrary trees and α=3 for arbitrary graphs. In the context of several case studies, we determine how localization accuracy is affected by various system parameters, including the structure of the network, the density of observers, and the number of observed cascades.

  19. Diffuse Large B-Cell Lymphoma Mimicking Schwannoma of Lumbar Spine

    PubMed Central

    Kim, Seung-Kook; Lee, Sun-Ho; Kim, Eun-Sang

    2016-01-01

    A rare case of solitary diffuse large B-cell lymphoma arising from the lumbar spinal nerve root is reported. A 37-year-old man presented with a 3-month history of progressive numbness and paraparesis in both legs. The initial diagnosis was benign primary intradural extramedullary tumor including schwannoma and meningioma. Histopathological examination revealed diffuse large B-cell lymphoma. While a well-defined T1 isointense mass is common in primary spinal schwannoma, the present case was atypical and had a yellowish neural component. The pathogenesis and radiological findings of spinal diffuse large B-cell lymphoma are discussed and related literature is reviewed. PMID:27437017

  20. An Alternative Analysis of Some Recent Diffusion Experiments on the Large Plasma Device

    SciTech Connect

    Simon, A.

    2008-04-07

    The results of a recent numerical analysis of a diffusion experiment on the large plasma device (LAPD) are re-examined. A simplified analytic solution of the transport equations is obtained by including previously omitted contributions to the transport. This solution strongly suggests that an accurate determination of the perpendicular diffusion coefficient would be very difficult in the specific LAPD experimental arrangement, due to near-cancellation of large terms. Thus, caution should be exercised in claiming that Bohm diffusion, or its suppression in the presence of a large applied radial voltage, has been observed.

  1. AIDS related knowledge and behaviours among college students, Gondar, Ethiopia: a comparative study.

    PubMed

    Teka, T

    1997-07-01

    AIDS-related knowledge and behaviours among students at the Gondar College of Medical Sciences, Gondar, Ethiopia were evaluated based on identical surveys conducted in 1990 and 1992. One hundred three second year students provided information in 1992. Analysis indicated that 49% were engaged in sexual intercourse and only a third of these group used condom despite their improved knowledge and belief on condom compared to their previous position in 1990 (p < 0.004). On the other hand, their sexual behaviours regarding sexual contact with high risk individuals decreased compared to 1990 (p < 0.0005). Their general level of AIDS-related preventive knowledge increased over time (p < 0.002), although there was no significant difference in knowledge observed among different sexes and departments. Among the sexually active, a large proportion of students (22%) still had sexual contact with high risk individuals and only 33% of them were using safer methods. Continuing efforts, including peer education, specific health education interventions are still crucially needed to bring a positive change in sexual behaviour. PMID:9558757

  2. Advective-diffusive motion on large scales from small-scale dynamics with an internal symmetry

    NASA Astrophysics Data System (ADS)

    Marino, Raffaele; Aurell, Erik

    2016-06-01

    We consider coupled diffusions in n -dimensional space and on a compact manifold and the resulting effective advective-diffusive motion on large scales in space. The effective drift (advection) and effective diffusion are determined as a solvability conditions in a multiscale analysis. As an example, we consider coupled diffusions in three-dimensional space and on the group manifold SO(3) of proper rotations, generalizing results obtained by H. Brenner [J. Colloid Interface Sci. 80, 548 (1981), 10.1016/0021-9797(81)90214-9]. We show in detail how the analysis can be conveniently carried out using local charts and invariance arguments. As a further example, we consider coupled diffusions in two-dimensional complex space and on the group manifold SU(2). We show that although the local operators may be the same as for SO(3), due to the global nature of the solvability conditions the resulting diffusion will differ and generally be more isotropic.

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

    PubMed

    Armitage, James O

    2012-02-01

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

  4. Detection of polyomavirus simian virus 40 tumor antigen DNA in AIDS-related systemic non-Hodgkin lymphoma

    NASA Technical Reports Server (NTRS)

    Vilchez, Regis A.; Lednicky, John A.; Halvorson, Steven J.; White, Zoe S.; Kozinetz, Claudia A.; Butel, Janet S.

    2002-01-01

    Systemic non-Hodgkin lymphoma (S-NHL) is a common malignancy during HIV infection, and it is hypothesized that infectious agents may be involved in the etiology. Epstein-Barr virus DNA is found in <40% of patients with AIDS-related S-NHL, suggesting that other oncogenic viruses, such as polyomaviruses, may play a role in pathogenesis. We analyzed AIDS-related S-NHL samples, NHL samples from HIV-negative patients, peripheral blood leukocytes from HIV-infected and -uninfected patients without NHL, and lymph nodes without tumors from HIV-infected patients. Specimens were examined by polymerase chain reaction analysis with use of primers specific for an N-terminal region of the oncoprotein large tumor antigen ( T-ag ) gene conserved among all three polyomaviruses (simian virus 40 [SV40], JC virus, and BK virus). Polyomavirus T-ag DNA sequences, proven to be SV40-specific, were detected more frequently in AIDS-related S-NHL samples (6 of 26) than in peripheral blood leukocytes from HIV-infected patients (6 of 26 vs. 0 of 69; p =.0001), NHL samples from HIV-negative patients (6 of 26 vs. 0 of 10; p =.09), or lymph nodes (6 of 26 vs. 0 of 7; p =.16). Sequences of C-terminal T-ag DNA from SV40 were amplified from two AIDS-related S-NHL samples. Epstein-Barr virus DNA sequences were detected in 38% (10 of 26) AIDS-related S-NHL samples, 50% (5 of 10) HIV-negative S-NHL samples, and 57% (4 of 7) lymph nodes. None of the S-NHL samples were positive for both Epstein-Barr virus DNA and SV40 DNA. Further studies of the possible role of SV40 in the pathogenesis of S-NHL are warranted.

  5. Bromodomain inhibition in diffuse large B-cell lymphoma--giving MYC a brake.

    PubMed

    Mottok, Anja; Gascoyne, Randy D

    2015-01-01

    Bromodomains are conserved protein regions that function as epigenetic readers by recognizing specific histone modifications. The common association of bromodomains with enhancer and super-enhancer regions in diffuse large B-cell lymphoma contributes to its pathogenesis. Bromodomain inhibition reduces tumor growth largely through the disruption of transcriptional networks driven by oncogenic MYC. PMID:25165099

  6. Measuring HIV/AIDS-Related Stigma across South Africa: A Versatile and Multidimensional Scale

    ERIC Educational Resources Information Center

    Smith, Edward A.; Miller, Jacqueline A.; Newsome, Valerie; Sofolahan, Yewande A.; Airhihenbuwa, Collins O.

    2014-01-01

    Reducing HIV/AIDS-related stigma is critical in the fight against HIV/AIDS. Although national campaigns and prevention programs have been implemented across South Africa to address this critical concern, assessing the impact of these initiatives is difficult as it requires that measurement of HIV/AIDS-related stigma is uniform and comparable…

  7. Large interface diffusion in endotaxial growth of MnP films on GaP substrates

    SciTech Connect

    Nateghi, N. Ménard, D.; Masut, R. A.

    2014-10-07

    The metal organic vapor deposition of MnP films on GaP (100) substrates is shown to have a substantial endotaxial component. A study of the growth time evolution of the endotaxial depths of MnP grains reveals a diffusion-controlled growth with a relatively large diffusion coefficient of Mn in GaP. The value (2.2 ± 1.5) × 10⁻¹⁵ (cm²/s) obtained at 650 °C is at least two orders of magnitude larger than the reported Mn diffusion in bulk GaP. GaP surface mounds provide further indirect evidence that this large diffusion coefficient is concurrent with the out-diffusion of Ga atoms at the growing MnP/GaP interface. No trace of dislocations could be observed at or near this interface, which strongly suggests that Mn diffusion occurs through vacant sites generated by the difference between the crystallographic structures of MnP and GaP.

  8. An experimental investigation of two large annular diffusers with swirling and distorted inflow

    NASA Technical Reports Server (NTRS)

    Eckert, W. T.; Johnston, J. P.; Simons, T. D.; Mort, K. W.; Page, V. R.

    1980-01-01

    Two annular diffusers downstream of a nacelle-mounted fan were tested for aerodynamic performance, measured in terms of two static pressure recovery parameters (one near the diffuser exit plane and one about three diameters downstream in the settling duct) in the presence of several inflow conditions. The two diffusers each had an inlet diameter of 1.84 m, an area ratio of 2.3, and an equivalent cone angle of 11.5, but were distinguished by centerbodies of different lengths. The dependence of diffuser performance on various combinations of swirling, radially distorted, and/or azimuthally distorted inflow was examined. Swirling flow and distortions in the axial velocity profile in the annulus upstream of the diffuser inlet were caused by the intrinsic flow patterns downstream of a fan in a duct and by artificial intensification of the distortions. Azimuthal distortions or defects were generated by the addition of four artificial devices (screens and fences). Pressure recovery data indicated beneficial effects of both radial distortion (for a limited range of distortion levels) and inflow swirl. Small amounts of azimuthal distortion created by the artificial devices produced only small effects on diffuser performance. A large artificial distortion device was required to produce enough azimuthal flow distortion to significantly degrade the diffuser static pressure recovery.

  9. Intravenous Chemotherapy or Oral Chemotherapy in Treating Patients With Previously Untreated Stage III-IV HIV-Associated Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-06-09

    AIDS-related Diffuse Large Cell Lymphoma; AIDS-related Diffuse Mixed Cell Lymphoma; AIDS-related Diffuse Small Cleaved Cell Lymphoma; AIDS-related Immunoblastic Large Cell Lymphoma; AIDS-related Lymphoblastic Lymphoma; AIDS-related Peripheral/Systemic Lymphoma; AIDS-related Small Noncleaved Cell Lymphoma; Stage III AIDS-related Lymphoma; Stage IV AIDS-related Lymphoma

  10. A case of primary adrenal diffuse large B-cell lymphoma in HIV.

    PubMed

    Malik, Seema; Chapman, Cordelia B-P; Drew, Olivia

    2016-07-01

    Primary adrenal diffuse large B-cell lymphoma in HIV is a very rare, highly aggressive extra-nodal lymphoma. There is only one previous case reported in the literature. Our patient presented with isolated bilateral adrenal masses with no lymphadenopathy or visceral involvement, which made the diagnosis challenging. PMID:26113518

  11. Analysis of FOXO1 mutations in diffuse large B-cell lymphoma | Office of Cancer Genomics

    Cancer.gov

    Abstract: Diffuse large B-cell lymphoma (DLBCL) accounts for 30% to 40% of newly diagnosed lymphomas and has an overall cure rate of approximately 60%. Previously, we observed FOXO1 mutations in non-Hodgkin lymphoma patient samples. To explore the effects of FOXO1 mutations, we assessed FOXO1 status in 279 DLBCL patient samples and 22 DLBCL-derived cell lines.

  12. Towards a minimal stochastic model for a large class of diffusion-reactions on biological membranes

    PubMed Central

    Chevalier, Michael W.; El-Samad, Hana

    2012-01-01

    Diffusion of biological molecules on 2D biological membranes can play an important role in the behavior of stochastic biochemical reaction systems. Yet, we still lack a fundamental understanding of circumstances where explicit accounting of the diffusion and spatial coordinates of molecules is necessary. In this work, we illustrate how time-dependent, non-exponential reaction probabilities naturally arise when explicitly accounting for the diffusion of molecules. We use the analytical expression of these probabilities to derive a novel algorithm which, while ignoring the exact position of the molecules, can still accurately capture diffusion effects. We investigate the regions of validity of the algorithm and show that for most parameter regimes, it constitutes an accurate framework for studying these systems. We also document scenarios where large spatial fluctuation effects mandate explicit consideration of all the molecules and their positions. Taken together, our results derive a fundamental understanding of the role of diffusion and spatial fluctuations in these systems. Simultaneously, they provide a general computational methodology for analyzing a broad class of biological networks whose behavior is influenced by diffusion on membranes. PMID:22938214

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

    NASA Technical Reports Server (NTRS)

    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.

  14. Whole-Body Diffusion-weighted Imaging in Hodgkin Lymphoma and Diffuse Large B-Cell Lymphoma.

    PubMed

    Toledano-Massiah, Sarah; Luciani, Alain; Itti, Emmanuel; Zerbib, Pierre; Vignaud, Alexandre; Belhadj, Karim; Baranes, Laurence; Haioun, Corinne; Lin, Chieh; Rahmouni, Alain

    2015-01-01

    Whole-body imaging, in particular molecular imaging with fluorine 18 ((18)F)-fluorodeoxyglucose (FDG) positron emission tomography (PET), is essential to management of lymphoma. The assessment of disease extent provided by use of whole-body imaging is mandatory for planning appropriate treatment and determining patient prognosis. Assessment of treatment response allows clinicians to tailor the treatment strategy during therapy if necessary and to document complete remission at the end of treatment. Because of rapid technical developments, such as echo-planar sequences, parallel imaging, multichannel phased-array surface coils, respiratory gating, and moving examination tables, whole-body diffusion-weighted (DW) magnetic resonance (MR) imaging that reflects cell density is now feasible in routine clinical practice. Whole-body DW MR imaging allows anatomic assessment as well as functional and quantitative evaluation of tumor sites by calculation of the apparent diffusion coefficient (ADC). Because of their high cellularity and high nucleus-to-cytoplasm ratio, lymphomatous lesions have low ADC values and appear hypointense on ADC maps. As a result, whole-body DW MR imaging with ADC mapping has become a promising tool for lymphoma staging and treatment response assessment. The authors review their 4 years of experience with 1.5-T and 3-T whole-body DW MR imaging used with (18)F-FDG PET/computed tomography at baseline, interim, and end of treatment in patients with Hodgkin lymphoma and diffuse large B-cell lymphoma and discuss the spectrum of imaging findings and potential pitfalls, limitations, and challenges associated with whole-body DW MR imaging in these patients. PMID:25815803

  15. Magnetospheric Multiscale Observations of the Electron Diffusion Region of Large Guide Field Magnetic Reconnection.

    PubMed

    Eriksson, S; Wilder, F D; Ergun, R E; Schwartz, S J; Cassak, P A; Burch, J L; Chen, L-J; Torbert, R B; Phan, T D; Lavraud, B; Goodrich, K A; Holmes, J C; Stawarz, J E; Sturner, A P; Malaspina, D M; Usanova, M E; Trattner, K J; Strangeway, R J; Russell, C T; Pollock, C J; Giles, B L; Hesse, M; Lindqvist, P-A; Drake, J F; Shay, M A; Nakamura, R; Marklund, G T

    2016-07-01

    We report observations from the Magnetospheric Multiscale (MMS) satellites of a large guide field magnetic reconnection event. The observations suggest that two of the four MMS spacecraft sampled the electron diffusion region, whereas the other two spacecraft detected the exhaust jet from the event. The guide magnetic field amplitude is approximately 4 times that of the reconnecting field. The event is accompanied by a significant parallel electric field (E_{∥}) that is larger than predicted by simulations. The high-speed (∼300  km/s) crossing of the electron diffusion region limited the data set to one complete electron distribution inside of the electron diffusion region, which shows significant parallel heating. The data suggest that E_{∥} is balanced by a combination of electron inertia and a parallel gradient of the gyrotropic electron pressure. PMID:27419573

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

    SciTech Connect

    Shea, Patrick Kreuzer, Hans Jürgen

    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.

  17. Magnetospheric Multiscale Observations of the Electron Diffusion Region of Large Guide Field Magnetic Reconnection

    NASA Astrophysics Data System (ADS)

    Eriksson, S.; Wilder, F. D.; Ergun, R. E.; Schwartz, S. J.; Cassak, P. A.; Burch, J. L.; Chen, L.-J.; Torbert, R. B.; Phan, T. D.; Lavraud, B.; Goodrich, K. A.; Holmes, J. C.; Stawarz, J. E.; Sturner, A. P.; Malaspina, D. M.; Usanova, M. E.; Trattner, K. J.; Strangeway, R. J.; Russell, C. T.; Pollock, C. J.; Giles, B. L.; Hesse, M.; Lindqvist, P.-A.; Drake, J. F.; Shay, M. A.; Nakamura, R.; Marklund, G. T.

    2016-07-01

    We report observations from the Magnetospheric Multiscale (MMS) satellites of a large guide field magnetic reconnection event. The observations suggest that two of the four MMS spacecraft sampled the electron diffusion region, whereas the other two spacecraft detected the exhaust jet from the event. The guide magnetic field amplitude is approximately 4 times that of the reconnecting field. The event is accompanied by a significant parallel electric field (E∥ ) that is larger than predicted by simulations. The high-speed (˜300 km /s ) crossing of the electron diffusion region limited the data set to one complete electron distribution inside of the electron diffusion region, which shows significant parallel heating. The data suggest that E∥ is balanced by a combination of electron inertia and a parallel gradient of the gyrotropic electron pressure.

  18. Project of a Large Superconductor Detector Involving Directed Diffusion of Hot Electrons and Microcalorimeter

    SciTech Connect

    Shpinel, V.S.

    2005-12-01

    In recent years, radically new detectors for soft x rays and gamma rays were developed on the basis of superconducting tunnel junctions. These detectors made it possible to attain a very high resolution, but their largest area is overly small for employing them in nuclear spectroscopy. This study is devoted to the problem of designing a superconductor detector whose dimensions are sufficiently large for detecting gamma rays and which is suitable for applications in various fields of science. The detector consists of three units: an absorber, a hot-electron calorimeter, and a tunnel-junction (normal metal-insulator-superconductor) thermometer. The absorber has a multilayer structure consisting of thin superconductor layers arranged in the order of variation of the superconductor energy gap. This structure specifies the direction of hot-electron diffusion. Since quasiparticles diffuse in a specific direction, the diffusion time becomes shorter than that in the case of conventional diffusion. It is necessary that this time be shorter than the time of electron-phonon interaction. Calculations of the diffusion time for the particular structure in question and data from the literature on electron-phonon interaction show that the operating area of the detector can be about 3 to 4 mm{sup 2} and that its thickness can be about 1 mm. These dimensions can be considerably increased in the case of especially pure superconductors.

  19. Balancing engagement/detachment in AIDS-related multiple losses.

    PubMed

    Carmack, B J

    1992-01-01

    The process gay persons use to manage the multiple losses and cumulative grief from losing lovers, friends, colleagues and clients to AIDS was explored. Interviews with gay individuals (n = 19) in a large urban area in the West provided data for conceptual coding and comparative analysis. Balancing engagement and detachment was identified as the basic social-psychological process that described how gay individuals struggled to reach an optimal balance in their involvement in the needs of individuals and the community. Four conceptual categories were identified: dysfunctional engagement, functional engagement, functional detachment and dysfunctional detachment. These four categories occur within the contexts of previous life style and redefinition of personal values. PMID:1541482

  20. Generation of Diffuse Large Volume Plasma by an Ionization Wave from a Plasma Jet

    NASA Astrophysics Data System (ADS)

    Laroussi, Mounir; Razavi, Hamid

    2015-09-01

    Low temperature plasma jets emitted in ambient air are the product of fast ionization waves that are guided within a channel of a gas flow, such as helium. This guided ionization wave can be transmitted through a dielectric material and under some conditions can ignite a discharge behind the dielectric material. Here we present a novel way to produce large volume diffuse low pressure plasma inside a Pyrex chamber that does not have any electrodes or electrical energy directly applied to it. The diffuse plasma is ignited inside the chamber by a plasma jet located externally to the chamber and that is physically and electrically unconnected to the chamber. Instead, the plasma jet is just brought in close proximity to the external wall/surface of the chamber or to a dielectric tubing connected to the chamber. The plasma thus generated is diffuse, large volume and with physical and chemical characteristics that are different than the external plasma jet that ignited it. So by using a plasma jet we are able to ``remotely'' ignite volumetric plasma under controlled conditions. This novel method of ``remote'' generation of a low pressure, low temperature diffuse plasma can be useful for various applications including material processing and biomedicine.

  1. Message spreading in networks with stickiness and persistence: Large clustering does not always facilitate large-scale diffusion

    NASA Astrophysics Data System (ADS)

    Cui, Pengbi; Tang, Ming; Wu, Zhi-Xi

    2014-09-01

    Recent empirical studies have confirmed the key roles of complex contagion mechanisms such as memory, social reinforcement, and decay effects in information diffusion and behavior spreading. Inspired by this fact, we here propose a new agent-based model to capture the whole picture of the joint action of the three mechanisms in information spreading, by quantifying the complex contagion mechanisms as stickiness and persistence, and carry out extensive simulations of the model on various networks. By numerical simulations as well as theoretical analysis, we find that the stickiness of the message determines the critical dynamics of message diffusion on tree-like networks, whereas the persistence plays a decisive role on dense regular lattices. In either network, the greater persistence can effectively make the message more invasive. Of particular interest is that our research results renew our previous knowledge that messages can spread broader in networks with large clustering, which turns out to be only true when they can inform a non-zero fraction of the population in the limit of large system size.

  2. Recurrent endobronchial diffuse large B-cell lymphoma. Diagnosed by cryoprobe.

    PubMed

    Pajares, Virginia; Torrego, Alfons; Granell, Miquel; Szafranska, Justyna; Mozos, Anna; Puzo, Carmen

    2013-05-01

    The bronchial involvement of diffuse large B-cell lymphoma (DLBCL) is an exceptional finding. Histological diagnosis is done with lung tissue samples. In these cases, the need for immunohistochemistry studies in order to establish the diagnosis requires obtaining tissue samples of adequate size and quality. Sometimes, endoscopic explorations may be repeated to obtain further biopsies. We present the first documented case of recurrent endobronchial DLBCL that was diagnosed from a bronchial biopsy taken with a cryoprobe. PMID:22981515

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

    PubMed

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

    2016-09-01

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

  4. Recent advances in the treatment of AIDS-related Kaposi's sarcoma.

    PubMed

    Cattelan, Anna M; Trevenzoli, Marco; Aversa, Savina M L

    2002-01-01

    Kaposi's sarcoma (KS) is the most common malignancy associated with HIV infection and is considered an AIDS defining condition by the US Centers of Disease Control Guidelines. Several advances in the treatment of AIDS-related KS have been achieved over the past few years, even though a gold standard therapy for KS has not yet been defined and treatment must be tailored to individual needs. Since the availability of highly active antiretroviral therapy (HAART), a dramatic clinical response has been documented in patients with KS, making HAART an essential approach in the management of KS in most, if not all, patients with AIDS-related KS. However, in case of aggressive, visceral, and/or life-threatening KS, more complex therapeutic schedules have to be taken into account, including chemotherapy, radiotherapy, and/or immunotherapy. In general, systemic treatment for KS is limited to widespread, symptomatic disease, whereas local interventions are indicated for minimal, cosmetically troublesome lesions. Among new cytotoxic agents, liposomal anthracyclines and paclitaxel are highly effective molecules for KS and have been approved by the US Food and Drug Administration (FDA) as first-line and second-line monotherapy, respectively, for advanced KS. Furthermore, a greater understanding of the pathogenesis of KS has lead to the development of an array of new experimental agents. Many antiangiogenic agents such as AGM 1470 (TNP 470), thalidomide, and glufanide disodium (IM 862) have produced encouraging responses in patients with KS and large clinical trials are in progress. Retinoic acids may also block neoangiogenesis as well as proliferation of KS cells in vitro, and they have been used either systemically or topically with a high response rate. Thus, a topical compound 0.1% alitretinoin gel was approved in 1999 by the FDA for the treatment of skin lesions associated with KS. Human chorionic gonadotropin, a hormonal agent, has shown a strong inhibitory activity in KS

  5. Whole blood EBV-DNA predicts outcome in diffuse large B-cell lymphoma.

    PubMed

    Tisi, Maria Chiara; Cupelli, Elisa; Santangelo, Rosaria; Maiolo, Elena; Alma, Eleonora; Giachelia, Manuela; Martini, Maurizio; Bellesi, Silvia; D'Alò, Francesco; Voso, Maria Teresa; Pompili, Maurizio; Leone, Giuseppe; Larocca, Luigi Maria; Hohaus, Stefan

    2016-03-01

    An association between Epstein-Barr Virus (EBV) infection and lymphoproliferative diseases has been reported with EBV + diffuse large B cell-lymphoma (DLBCL) of the elderly described as a distinct entity. In a cohort of 218 human immunodeficiency virus (HIV)-negative patients with diffuse large B-cell lymphomas, we detected EBV-DNA in 25% of whole blood (WB) samples at diagnosis. Presence and viral load in WB, mononuclear cells or plasma did not predict the presence of EBV in the tumor biopsy. Positive Hepatitis C virus (HCV) serology was associated with a higher frequency of EBV in WB. Patients with EBV-DNA in WB had a significantly shorter progression-free (p = 0.02) and overall survival (p = 0.05) after immunochemotherapy with R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisolone). We conclude that detection of EBV in WB is not a surrogate marker for EBV-association in diffuse large B-cell lymphoma, however it associates with worse outcome. PMID:26458141

  6. Large-eddy simulation of flow through a plane, asymmetric diffuser

    NASA Technical Reports Server (NTRS)

    Kaltenbach, Hans-Jakob

    1994-01-01

    A challenge for traditional turbulence modeling, based on the Reynolds averaged Navier-Stokes equations, remains the accurate prediction of 'mild', adverse pressure-gradient driven separation from a smooth surface. With this study we want to explore the capability of large-eddy simulation to predict the separation which occurs on the deflected wall of an asymmetric, plane diffuser with opening angle of 10 deg. The flow through the plane diffuser exhibits some additional interesting physical phenomena which make it a challenging test case. In addition to 'mild' separation about halfway down the deflected ramp, the flow is characterized by a small backflow zone with stalled fluid in the rear part of the expanding section. The turbulent flow entering the diffuser is subject to combined adverse and radial pressure gradients stemming from the convex curvature. Finally the flow recovers into a developed, turbulent channel flow in the outlet section. Obi et al. provide measurements of mean flow, Reynolds stresses, and pressure recovery, which were obtained by means of LDV in a wind tunnel. The objective of this study is to investigate whether LES with the standard dynamic model is able to accurately predict the flow in the one-sided diffuser and to explore the resolution requirements and associated costs.

  7. Fermi large area telescope measurements of the diffuse gamma-ray emission at intermediate galactic latitudes.

    PubMed

    Abdo, A A; Ackermann, M; Ajello, M; Anderson, B; Atwood, W B; Axelsson, M; 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; Caliandro, G A; Cameron, R A; Caraveo, P A; Casandjian, J M; Cecchi, C; Charles, E; Chekhtman, A; Cheung, C C; Chiang, J; Ciprini, S; Claus, R; Cohen-Tanugi, J; Conrad, J; Dereli, H; Dermer, C D; de Angelis, A; de Palma, F; Digel, S W; Di Bernardo, G; Dormody, M; do Couto e Silva, E; Drell, P S; Dubois, R; Dumora, D; Edmonds, Y; Farnier, C; Favuzzi, C; Fegan, S J; Focke, W B; Frailis, M; Fukazawa, Y; Funk, S; Fusco, P; Gaggero, D; Gargano, F; Gehrels, N; Germani, S; Giebels, B; Giglietto, N; Giordano, F; Glanzman, T; Godfrey, G; Grenier, I A; Grondin, M-H; Grove, J E; Guillemot, L; Guiriec, S; Hanabata, Y; Harding, A K; Hayashida, M; Hays, E; Hughes, R E; 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; 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; Nuss, E; Ohsugi, T; Okumura, A; 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; 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; Smith, D A; Smith, P D; Spandre, G; Spinelli, P; Starck, J-L; Stecker, F W; Striani, E; Strickman, M S; Strong, A W; Suson, D J; Tajima, H; Takahashi, H; 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

    2009-12-18

    The diffuse galactic gamma-ray emission is produced by cosmic rays (CRs) interacting with the interstellar gas and radiation field. Measurements by the Energetic Gamma-Ray Experiment Telescope (EGRET) instrument on the Compton Gamma-Ray Observatory indicated excess gamma-ray emission greater, > or approximately equal to 1 GeV relative to diffuse galactic gamma-ray emission models consistent with directly measured CR spectra (the so-called "EGRET GeV excess"). The Large Area Telescope (LAT) instrument on the Fermi Gamma-Ray Space Telescope has measured the diffuse gamma-ray emission with improved sensitivity and resolution compared to EGRET. We report on LAT measurements for energies 100 MeV to 10 GeV and galactic latitudes 10 degrees < or = |b| < or = 20 degrees. The LAT spectrum for this region of the sky is well reproduced by a diffuse galactic gamma-ray emission model that is consistent with local CR spectra and inconsistent with the EGRET GeV excess. PMID:20366246

  8. Fermi Large Area Telescope Measurements of the Diffuse Gamma-Ray Emission at Intermediate Galactic Latitudes

    NASA Astrophysics Data System (ADS)

    Abdo, A. A.; Ackermann, M.; Ajello, M.; Anderson, B.; Atwood, W. B.; Axelsson, M.; 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.; Caliandro, G. A.; Cameron, R. A.; Caraveo, P. A.; Casandjian, J. M.; Cecchi, C.; Charles, E.; Chekhtman, A.; Cheung, C. C.; Chiang, J.; Ciprini, S.; Claus, R.; Cohen-Tanugi, J.; Conrad, J.; Dereli, H.; Dermer, C. D.; de Angelis, A.; de Palma, F.; Digel, S. W.; di Bernardo, G.; Dormody, M.; Do Couto E Silva, E.; Drell, P. S.; Dubois, R.; Dumora, D.; Edmonds, Y.; Farnier, C.; Favuzzi, C.; Fegan, S. J.; Focke, W. B.; Frailis, M.; Fukazawa, Y.; Funk, S.; Fusco, P.; Gaggero, D.; Gargano, F.; Gehrels, N.; Germani, S.; Giebels, B.; Giglietto, N.; Giordano, F.; Glanzman, T.; Godfrey, G.; Grenier, I. A.; Grondin, M.-H.; Grove, J. E.; Guillemot, L.; Guiriec, S.; Hanabata, Y.; Harding, A. K.; Hayashida, M.; Hays, E.; Hughes, R. E.; 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.; 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.; Nuss, E.; Ohsugi, T.; Okumura, A.; 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.; 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.; Smith, D. A.; Smith, P. D.; Spandre, G.; Spinelli, P.; Starck, J.-L.; Stecker, F. W.; Striani, E.; Strickman, M. S.; Strong, A. W.; Suson, D. J.; Tajima, H.; Takahashi, H.; 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.

    2009-12-01

    The diffuse galactic γ-ray emission is produced by cosmic rays (CRs) interacting with the interstellar gas and radiation field. Measurements by the Energetic Gamma-Ray Experiment Telescope (EGRET) instrument on the Compton Gamma-Ray Observatory indicated excess γ-ray emission ≳1GeV relative to diffuse galactic γ-ray emission models consistent with directly measured CR spectra (the so-called “EGRET GeV excess”). The Large Area Telescope (LAT) instrument on the Fermi Gamma-Ray Space Telescope has measured the diffuse γ-ray emission with improved sensitivity and resolution compared to EGRET. We report on LAT measurements for energies 100 MeV to 10 GeV and galactic latitudes 10°≤|b|≤20°. The LAT spectrum for this region of the sky is well reproduced by a diffuse galactic γ-ray emission model that is consistent with local CR spectra and inconsistent with the EGRET GeV excess.

  9. Fermi Large Area Telescope Measurements of the Diffuse Gamma-Ray Emission at Intermediate Galactic Latitudes

    SciTech Connect

    Abdo, A.A.; Ackermann, M.; Ajello, M.; Anderson, B.; Atwood, W.B.; Axelsson, M.; 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.; /more authors..

    2012-04-11

    The diffuse galactic {gamma}-ray emission is produced by cosmic rays (CRs) interacting with the interstellar gas and radiation field. Measurements by the Energetic Gamma-Ray Experiment Telescope (EGRET) instrument on the Compton Gamma-Ray Observatory indicated excess {gamma}-ray emission {ge}1 GeV relative to diffuse galactic {gamma}-ray emission models consistent with directly measured CR spectra (the so-called 'EGRET GeV excess'). The Large Area Telescope (LAT) instrument on the Fermi Gamma-Ray Space Telescope has measured the diffuse {gamma}-ray emission with improved sensitivity and resolution compared to EGRET. We report on LAT measurements for energies 100 MeV to 10 GeV and galactic latitudes 10{sup o} {le} |b| {le} 20{sup o}. The LAT spectrum for this region of the sky is well reproduced by a diffuse galactic {gamma}-ray emission model that is consistent with local CR spectra and inconsistent with the EGRET GeV excess.

  10. Biogeochemical Evidence of Large Vertical Eddy Diffusivity Associated With Subtropical Mode Water of the North Pacific

    NASA Astrophysics Data System (ADS)

    Suga, T.; Sukigara, C.; Saino, T.; Toyama, K.; Yanagimoto, D.; Hanawa, K.; Shikama, N.; Ishizu, M.

    2008-12-01

    Based on the extensive profiling float observation carried out as part of the Kuroshio Extension System Study (KESS), Qiu et al. (2006) reported large vertical eddy diffusivity (2-5 x10-4 m2s-1) near the upper boundary of Subtropical Mode Water (STMW). This large diffusivity possibly have an impact on subsurface redistribution of heat, nutrients and dissolved gas components, etc., in the subtropical ocean. On the other hand, recent measurement of turbulent kinetic energy dissipation rate by Mori et al. (2008) indicates much smaller vertical eddy diffusivity (10-7 - 10-5 m2s-1) over the whole depth range of STMW. However, the direct comparison between the estimation by Qiu et al. and that by Mori et al. is possibly inappropriate because the former is based on the PV change over a couple of months and the latter on the instantaneous turbulent measurements. We carried out physical and biogeochemical observation to examine the vertical diffusivity near the top of STMW using a profiling float. The profiling float, which was equipped with a fluorometer and a dissolved oxygen sensor along with temperature and salinity sensors, was deployed in the STMW formation region and acquired quasi-Lagrangian, 5-day-interval time-series records from March to July in 2006. The time-series distribution of chl.a showed a sustained and sizable deep chlorophyll maximum just above the upper boundary of the STMW throughout early summer. Vertically integrated chlorophyll in this period was consistently ranging from 15-30 mgm-2, indicating sustained primary production and a continuous supply of nutrients ranging from 10-20 mgNm-2day-1. The time-series data indicate no sporadic events to supply nutrients and instead support, along with vertical profiles of nitrate obtained by ship-board measurements near the float, the large vertical diffusivity reported by Qiu et al. Since our estimation of vertical diffusivity is based on temporal evolution of primary production over several weeks, it is

  11. Large-scale patterns in summer diffusive CH4 fluxes across boreal lakes, and contribution to diffusive C emissions.

    PubMed

    Rasilo, Terhi; Prairie, Yves T; Del Giorgio, Paul A

    2015-03-01

    Lakes are a major component of boreal landscapes, and whereas lake CO2 emissions are recognized as a major component of regional C budgets, there is still much uncertainty associated to lake CH4 fluxes. Here, we present a large-scale study of the magnitude and regulation of boreal lake summer diffusive CH4 fluxes, and their contribution to total lake carbon (C) emissions, based on in situ measurements of concentration and fluxes of CH4 and CO2 in 224 lakes across a wide range of lake type and environmental gradients in Québec. The diffusive CH4 flux was highly variable (mean 11.6 ± 26.4 SD mg m(-2)  d(-1) ), and it was positively correlated with temperature and lake nutrient status, and negatively correlated with lake area and colored dissolved organic matter (CDOM). The relationship between CH4 and CO2 concentrations fluxes was weak, suggesting major differences in their respective sources and/or regulation. For example, increasing water temperature leads to higher CH4 flux but does not significantly affect CO2 flux, whereas increasing CDOM concentration leads to higher CO2 flux but lower CH4 flux. CH4 contributed to 8 ± 23% to the total lake C emissions (CH4  + CO2 ), but 18 ± 25% to the total flux in terms of atmospheric warming potential, expressed as CO2 -equivalents. The incorporation of ebullition and plant-mediated CH4 fluxes would further increase the importance of lake CH4 . The average Q10 of CH4 flux was 3.7, once other covarying factors were accounted for, but this apparent Q10 varied with lake morphometry and was higher for shallow lakes. We conclude that global climate change and the resulting shifts in temperature will strongly influence lake CH4 fluxes across the boreal biome, but these climate effects may be altered by regional patterns in lake morphometry, nutrient status, and browning. PMID:25220765

  12. Large Area Transition Edge Sensor X-ray Microcalorimeters for Diffuse X-ray Background Studies

    NASA Astrophysics Data System (ADS)

    Morgan, K. M.; Busch, S. E.; Eckart, M. E.; Kilbourne, C. A.; McCammon, D.

    2014-08-01

    We are developing transition edge sensor (TES) mirocalorimeters with large area (0.72 mm) absorbers to study the keV diffuse X-ray background. The goal is to develop a 2 cm array of 256 pixels for a sounding rocket payload. We present a pixel design which includes a Mo/Au bilayer TES coupled to a large (850 x 850 x 0.2 m) gold absorber. Our simulations indicate that such a design can achieve energy resolution as good as 1.6 eV FWHM in our target bandpass of 0.05-1 keV. Additionally, thermal modelling shows that for typical gold layers, the position-dependent variation of the pulse shape over the large area of the absorber is not expected to significantly degrade this energy resolution. An array of devices will be fabricated in late 2013 to test this design.

  13. Balbiani Ring mRNPs Diffuse through and Bind to Clusters of Large Intranuclear Molecular Structures

    PubMed Central

    Veith, Roman; Sorkalla, Thomas; Baumgart, Eugen; Anzt, Johannes; Häberlein, Hanns; Tyagi, Sanjay; Siebrasse, Jan Peter; Kubitscheck, Ulrich

    2010-01-01

    A detailed conception of intranuclear messenger ribonucleoprotein particle (mRNP) dynamics is required for the understanding of mRNP processing and gene expression outcome. We used complementary state-of-the-art fluorescence techniques to quantify native mRNP mobility at the single particle level in living salivary gland cell nuclei. Molecular beacons and fluorescent oligonucleotides were used to specifically label BR2.1 mRNPs by an in vivo fluorescence in situ hybridization approach. We characterized two major mobility components of the BR2.1 mRNPs. These components with diffusion coefficients of 0.3 ± 0.02 μm2/s and 0.73 ± 0.03 μm2/s were observed independently of the staining method and measurement technique used. The mobility analysis of inert tracer molecules revealed that the gland cell nuclei contain large molecular nonchromatin structures, which hinder the mobility of large molecules and particles. The mRNPs are not only hindered by these mobility barriers, but in addition also interact presumably with these structures, what further reduces their mobility and effectively leads to the occurrence of the two diffusion coefficients. In addition, we provide evidence that the remarkably high mobility of the large, 50 nm-sized BR2.1 mRNPs was due to the absence of retarding chromatin. PMID:20959109

  14. Unusually Aggressive Primary Testicular Diffuse Large B Cell Lymphoma with Post Therapy Extensive Metastasis

    PubMed Central

    Goel, Shalini; Mohapatra, Ishani; Gajendra, Smeeta; Gupta, Sunil

    2016-01-01

    Primary Testicular Lymphoma (PTL) is a rare intermediate to high grade tumour, diffuse large cell being the most common type. Unlike nodal Diffuse Large B-Cell Lymphoma (DLBCL), testicular DLBCL has a less aggressive course and better prognosis. Metastasis is uncommon in testicular DLBCL. Commonly involved sites are contralateral testes, Waldeyer’s ring, skin, lung, Central Nervous System (CNS) and prostate, however the kidneys, liver, bone marrow, pleura and bones are more rarely involved. We report a case of testicular DLBCL which has metastasized to skin and bone marrow with an aggressive clinical course in a year, in-spite of combined modality of therapy given to the patient. Bone marrow infiltration is common and well documented with nodal DLBCL, however there is no published literature for simultaneous bone marrow and skin infiltration in testicular DLBCL till date. Other large studies done in the west have shown that distinct metastasis is usually common but the median progression-free survival is usually in years. This case stresses on shorter period of progression after standard treatment protocol in this part of the world, thus highlighting the need for other extensive studies to define specific treatment protocol for testicular DLBCL.

  15. A case of primary pulmonary diffuse large B-cell lymphoma diagnosed by transbronchial biopsy.

    PubMed

    Yoshino, Naoyuki; Hirata, Tomomi; Takeuchi, Chie; Usuda, Jitsuo; Hosone, Masaru

    2015-01-01

    A 76-year-old man took a chest X-ray for his medical checkup and an abnormal shadow was detected in the right lower lung field. For more detailed examination, he was referred to our hospital. Chest computed tomography showed a 20-mm nodule with relatively regular margins in the right lower lobe. A compact proliferation of circular to polygonal cells with a high nucleus-cytoplasm ratio was evident in a transbronchial lung biopsy. Based on pathological findings, a mature large B-cell lymphoma was diagnosed. Thoracoscopic right lower lobectomy and mediastinal lymphadenectomy were performed. The post-surgical pathological examination showed that the tumor consisted of diffuse to compact proliferation of medium to large atypical lymphocyte-like cells. Immunohistochemical staining yielded positive results for B-cell lineage markers. Five months after surgical resection, neither local recurrence nor accumulation in remote organs was observed on gallium scintigraphy. The diagnosis of primary pulmonary diffuse large B-cell lymphoma was established. PMID:25912218

  16. Rare clinical presentation of diffuse large B-cell lymphoma as otitis media and facial palsy

    PubMed Central

    Siddiahgari, Sirisha Rani; Yerukula, Pallavi; Lingappa, Lokesh; Moodahadu, Latha S.

    2016-01-01

    Extra nodal presentation of Non Hodgkins Lymphoma (NHL) is a rare entity, and data available about the NHL that primarily involves of middle ear and mastoid is limited. We report a case of diffuse large B cell lymphoma (DLBCL), in a 2 year 8 month old boy, who developed otalgia and facial palsy. Computed tomography revealed a mass in the left mastoid. Mastoid exploration and histopathological examination revealed DLBCL. This case highlights the importance of considering malignant lymphoma as one of the differential diagnosis in persistent otitis media and/facial palsy. PMID:27195036

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

    PubMed

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

    2014-01-01

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

  18. Primary diffuse large B-cell lymphoma associated with chronic osteomyelitis of the knee.

    PubMed

    Romero-Rojas, Alfredo E; Diaz-Perez, Julio A; Raju, Sharat; Messa-Botero, Oscar; Prieto-Bletan, Andres; Criollo-Palacios, Felipe

    2014-12-01

    Diffuse large B-cell lymphoma (DLBCL) associated with chronic inflammation is a recently adopted category of DLBCL, which describes an aggressive B-cell lymphoma raised in the setting of non-immune chronic inflammation. Primary presentation of this subtype of DLBCL in bone is extremely rare. Here, we present the case of a 27 year old woman with DLBCL of the right distal femur, identified after a three-year history of chronic osteomyelitis. In this report, we describe the clinical and histopathologic features of this unusual presentation of DLBCL and discuss aspects relevant to diagnosis and treatment of this entity. PMID:25199714

  19. Diffuse Large B-cell lymphoma: Prognostic markers and their impact on therapy.

    PubMed

    Jamil, Muhammad O; Mehta, Amitkumar

    2016-05-01

    Diffuse large B-cell lymphoma (DLBCL) is the most common type of Non-Hodgkin lymphoma (NHL). DLBCL is clinically, pathologically and molecularly heterogeneous disease. Various clinical, pathological and molecular markers have been developed to characterize the disease. Based on these characterizations, new targeted agents are being investigated to optimize the treatment and improve the outcomes of DLBCL. Enhanced molecular understanding, invention of targeted agents and immunotherapy has opened the doors for improvement in the treatment of DLBCL. In this review, we will discuss various prognostic markers of DLBCL and their potential therapeutic implications. PMID:26808217

  20. Highly transparent sapphire micro-grating structures with large diffuse light scattering

    NASA Astrophysics Data System (ADS)

    Ko, Yeong Hwan; Yu, Jae Su

    2011-08-01

    The highly transparent micro-grating structures (MGSs) of sapphire substrate with large diffuse light scattering were theoretically and experimentally studied. From the finite difference time domain simulation, it was found that the degree of diffuse light scattering is strongly dependent on the size of grating structures. For a highly transparent property, the sapphire MGSs were optimally designed by the theoretical calculations using the rigorous coupled wave analysis method. The order of taper, geometry (i.e., width and height), and pitch length of MGSs were optimized to maximize their average total transmittance over a wide wavelength range of 300-1800 nm. Additionally, the influence of the deposition of low-refractive index material such as SiO2 onto sapphire MGSs on the transmittance characteristics was investigated. To verify experimentally the feasibility, the sapphire MGSs were fabricated by the conventional lithography and dry etching processes. The SiO2 deposited sapphire MGS exhibited a further increase in the total transmittance due to its relatively more graded refractive index profile while maintaining a significantly enhanced diffuse light scattering. The experimental data were in a reasonable agreement with the theoretical results.

  1. Electric fields and large-scale undulations in the evening sector of the diffuse auroral zone

    NASA Astrophysics Data System (ADS)

    Baishev, D. G.; Barkova, E. S.; Stepanov, A. E.; Rich, F.; Yumoto, K.

    2010-02-01

    The synchronous observations of strong electric fields and large-scale undulations observed on December 12, 2004, in the evening sector of the diffuse auroral zone 0900-1000 UT (~1700-1800 MLT) have been analyzed. The appearance of strong northward electric field at ~0900 UT was almost simultaneously registered at Tixie Bay ionospheric station (71.6° N, 128.9° E, L =, 5.6) and on the DMSP F15 satellite. At 0910-1000 UT, the all-sky TV camera at Tixie Bay and the DMSP satellites (F13, F14, and F15) registered eight undulations propagating westward at a velocity of 0.7—0.8 km/s. The undulation parameters registered during the TV observations agree with the satellite measurements. The distinctive feature of the analyzed event consists in that an intense electric field and undulations were localized within the diffuse zone in the region of increased precipitation of keV electrons. A comparison of the ground-based and satellite measurements made it possible to draw the conclusion on the necessary conditions for formation of diffuse undulations.

  2. Diffuse pollution of soil and water: Long term trends at large scales?

    NASA Astrophysics Data System (ADS)

    Grathwohl, P.

    2012-04-01

    Industrialization and urbanization, which consequently increased pressure on the environment to cause degradation of soil and water quality over more than a century, is still ongoing. The number of potential environmental contaminants detected in surface and groundwater is continuously increasing; from classical industrial and agricultural chemicals, to flame retardants, pharmaceuticals, and personal care products. While point sources of pollution can be managed in principle, diffuse pollution is only reversible at very long time scales if at all. Compounds which were phased out many decades ago such as PCBs or DDT are still abundant in soils, sediments and biota. How diffuse pollution is processed at large scales in space (e.g. catchments) and time (centuries) is unknown. The relevance to the field of processes well investigated at the laboratory scale (e.g. sorption/desorption and (bio)degradation kinetics) is not clear. Transport of compounds is often coupled to the water cycle and in order to assess trends in diffuse pollution, detailed knowledge about the hydrology and the solute fluxes at the catchment scale is required (e.g. input/output fluxes, transformation rates at the field scale). This is also a prerequisite in assessing management options for reversal of adverse trends.

  3. Diffusion characteristics of large molecules assessed by proton MRS on a whole-body MR system.

    PubMed

    Lehnert, A; Machann, J; Helms, G; Claussen, C D; Schick, F

    2004-01-01

    Methods for examinations of diffusion of large molecules of the size of fatty acids or triglycerides were developed for whole body MR units. Samples of aliphatic molecules were examined to study the influence of chain length. Feasibility under in vivo conditions was tested on lard samples at 37 degrees C and on human subjects Three stimulated echo sequences with maximum b-values of 2000 s/mm(2), 20000 s/mm(2), and 80000 s/mm(2) were used to assess a wide range of mobility. Sequence timing was optimized to minimize relaxation losses of fatty tissue. Apparent diffusion coefficients (ADC) were determined from five spectra with different diffusion weighting. In-vitro experiments were performed on butanol, decanol, and oleic acid to study the influence of chain length. In vivo conditions were mimicked using lard at 37 degrees C representing a composition of substances of various chain lengths. Subcutaneous fat and tibial bone marrow were studied in three healthy volunteers. ADC of muscular lipids of the lower leg was determined in two subjects. ADC values of pure aliphatic substances were in the range between 3.2 x 10(-5) mm(2)/s for oleic acid and 37.8 x 10(-5) mm(2)/s for butanol. In vivo investigations revealed ADC values of 1.11-1.24 x 10(-5) mm(2)/s for tibial bone marrow and 1.21-2.05 x 10(-5) mm(2)/s for subcutaneous fat. Diffusion coefficients of extra- and intramyocellular lipids were 1.83-3.65 x 10(-5) mm(2)/s and 2.22-3.60 x 10(-5) mm(2)/s, respectively. The proposed technique enables determination of ADC values of relatively large molecules and of lipid tissue compartments under in vivo conditions. Diffusion properties in several human lipid compartments are reported for the first time. Incoherent voxel motion influences the in vivo results to an unknown degree because of high motion sensitivity. In vitro experiments revealed ADC values depending on the chain length of the substances, indicating a residual dependence of measured ADC's on sequence timing

  4. Crowding Induces Complex Ergodic Diffusion and Dynamic Elongation of Large DNA Molecules

    PubMed Central

    Chapman, Cole D.; Gorczyca, Stephanie; Robertson-Anderson, Rae M.

    2015-01-01

    Despite the ubiquity of molecular crowding in living cells, the effects of crowding on the dynamics of genome-sized DNA are poorly understood. Here, we track single, fluorescent-labeled large DNA molecules (11, 115 kbp) diffusing in dextran solutions that mimic intracellular crowding conditions (0–40%), and determine the effects of crowding on both DNA mobility and conformation. Both DNAs exhibit ergodic Brownian motion and comparable mobility reduction in all conditions; however, crowder size (10 vs. 500 kDa) plays a critical role in the underlying diffusive mechanisms and dependence on crowder concentration. Surprisingly, in 10-kDa dextran, crowder influence saturates at ∼20% with an ∼5× drop in DNA diffusion, in stark contrast to exponentially retarded mobility, coupled to weak anomalous subdiffusion, with increasing concentration of 500-kDa dextran. Both DNAs elongate into lower-entropy states (compared to random coil conformations) when crowded, with elongation states that are gamma distributed and fluctuate in time. However, the broadness of the distribution of states and the time-dependence and length scale of elongation length fluctuations depend on both DNA and crowder size with concentration having surprisingly little impact. Results collectively show that mobility reduction and coil elongation of large crowded DNAs are due to a complex interplay between entropic effects and crowder mobility. Although elongation and initial mobility retardation are driven by depletion interactions, subdiffusive dynamics, and the drastic exponential slowing of DNA, up to ∼300×, arise from the reduced mobility of larger crowders. Our results elucidate the highly important and widely debated effects of cellular crowding on genome-sized DNA. PMID:25762333

  5. CD20-negative diffuse large B-cell lymphomas: biology and emerging therapeutic options.

    PubMed

    Castillo, Jorge J; Chavez, Julio C; Hernandez-Ilizaliturri, Francisco J; Montes-Moreno, Santiago

    2015-06-01

    CD20-negative diffuse large B-cell lymphoma (DLBCL) is a rare and heterogeneous group of lymphoproliferative disorders. Known variants of CD20-negative DLBCL include plasmablastic lymphoma, primary effusion lymphoma, large B-cell lymphoma arising in human herpesvirus 8-associated multicentric Castleman disease and anaplastic lymphoma kinase-positive DLBCL. Given the lack of CD20 expression, atypical cellular morphology and aggressive clinical behavior characterized by chemotherapy resistance and inferior survival rates, CD20-negative DLBCL represents a challenge from the diagnostic and therapeutic perspectives. The goals of the present review are to summarize the current knowledge on the biology of the distinct variants of CD20-negative DLBCL, provide future therapeutic directions based on the limited preclinical and clinical data available, and increase awareness concerning these rare malignancies among pathologists and clinicians. PMID:25641215

  6. Large Eddy Simulation of Gravitational Effects on Transitional and Turbulent Gas-Jet Diffusion Flames

    NASA Technical Reports Server (NTRS)

    Givi, Peyman; Jaberi, Farhad A.

    2001-01-01

    The basic objective of this work is to assess the influence of gravity on "the compositional and the spatial structures" of transitional and turbulent diffusion flames via large eddy simulation (LES), and direct numerical simulation (DNS). The DNS is conducted for appraisal of the various closures employed in LES, and to study the effect of buoyancy on the small scale flow features. The LES is based on our "filtered mass density function"' (FMDF) model. The novelty of the methodology is that it allows for reliable simulations with inclusion of "realistic physics." It also allows for detailed analysis of the unsteady large scale flow evolution and compositional flame structure which is not usually possible via Reynolds averaged simulations.

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

    PubMed

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

    2008-02-01

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

  8. Numerical investigation of high pressure and high Reynolds diffusion flame using Large Eddy Simulation

    NASA Astrophysics Data System (ADS)

    Nichkoohi, Ali Lohrasbi; Tousi, Abolghasem Mesgarpour

    2014-10-01

    Today, with nonstop improvement in computational power, Large-Eddy Simulation (LES) is a high demanding research tool for predicting engineering flows. Such flows on high pressure condition like diesel engines is extensively employed in ground and marine transportation, oblige the designer to control and predict toxic pollutants, while maintaining or improving their high thermal efficiency. This becomes one of the main challenging issues in decades. In the present work, numerical investigation of diffusion flame dynamics is performed in the near-field of high-Reynolds jet flow on high pressure condition encountered in diesel engine applications. This work discusses the implementation of Partially Stirred Reactor (PaSR) combustion model by the approaches of large eddy simulation (LES). The simulation results show that LES, in comparison with Reynolds-Averaged Navier-Stokes (RANS) simulation predicts and captures transient phenomena very well. These phenomena such as unsteadiness and curvature are inherent in the near-field of high Reynolds diffusion flame. The outcomes of this research are compared and validated by other researchers' results. Detailed comparisons of the statistics show good agreement with the corresponding experiments.

  9. Large amplitude undulations of evening site diffuse aurorae. Optical characteristics and conditions of generation

    NASA Astrophysics Data System (ADS)

    Vorobjev, V. G.; Roldugin, V. C.; Yagodkina, O. I.

    2015-01-01

    Optical characteristics of large amplitude undulations (LAU) of diffuse aurorae observed by all-sky cameras at Kola Peninsula on December 28, 2010 were examined. Both interplanetary medium conditions and characteristics of magnetic activity before and during LAU were analyzed. It was shown that the development of undulations could be activated by sharp short-living of ˜20 minutes solar wind dynamic pressure impulse and existence of the undulations during about two hours was supported by electric field of stationary magnetospheric convection originated from large smoothly changed southward IMF Bz component of about -12nT. The altitude of undulation luminosity determined by triangulation method was 120 ± 10 km. The undulations amplitude changed from about 100 to 300 km and the average wavelength was ˜250 km. The undulations were observed moving westward with the average phase velocity of ˜0.7 km/s. The pass of DMSP F16 spacecraft just along "the tongue" of undulations showed that the wave of luminosity was located in the region of the predominantly ion (proton) precipitation with the average energy of particles of ˜18 keV. Rayed auroral structures were observed continuously in the region of diffuse aurorae during time interval of LAU existence. These structures were observed moving westward with the velocity of about 2 km/s that corresponds to the northward electric field of ˜100 mV/m.

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

    PubMed Central

    Deng, Lijuan; Wang, Xiaoxiao; Manyam, Ganiraju C.; Visco, Carlo; Montes-Moreno, Santiago; Zhang, Li; Dybkær, Karen; Chiu, April; Orazi, Attilio; Zu, Youli; Bhagat, Govind; Richards, Kristy L.; Hsi, Eric D.; Choi, William W.L.; van Krieken, J. Han; Huh, Jooryung; Ponzoni, Maurilio; Ferreri, Andrés J.M.; Parsons, Ben M.; Møller, Michael B.; Piris, Miguel A.; Winter, Jane N.; Medeiros, L. Jeffrey; Hu, Shimin; Young, Ken H.

    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 and BCL6 in 898 patients with de novo diffuse large B-cell lymphoma treated with standard chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab). Neither BCL6 translocation alone (more frequent in activated B-cell like diffuse large B-cell lymphoma) nor in combination with MYC translocation (observed in 2.0% of diffuse large B-cell lymphoma) predicted poorer survival in diffuse large B-cell lymphoma patients. Diffuse large B-cell lymphoma patients with MYC/BCL6 co-expression did have significantly poorer survival, however, MYC/BCL6 co-expression had no effect on prognosis in the absence of MYC/BCL2 co-expression, and had no additive impact in MYC+/BCL2+ cases. The isolated MYC+/BCL6+/BCL2− subset, more frequent in germinal center B-cell like diffuse large B-cell lymphoma, had significantly better survival compared with the isolated MYC+/BCL2+/BCL6− subset (more 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 needs to be refined based on the specific genetic abnormalities present in these tumors. PMID:26573234

  11. Anomalous diffusion with under- and overshooting subordination: a competition between the very large jumps in physical and operational times.

    PubMed

    Stanislavsky, Aleksander; Weron, Karina

    2010-11-01

    In this paper we present an approach to anomalous diffusion based on subordination of stochastic processes. Application of such a methodology to analysis of the diffusion processes helps better understanding of physical mechanisms underlying the nonexponential relaxation phenomena. In the subordination framework we analyze a coupling between the very large jumps in physical and two different operational times, modeled by under- and overshooting subordinators, respectively. We show that the resulting diffusion processes display features by means of which all experimentally observed two-power-law dielectric relaxation patterns can be explained. We also derive the corresponding fractional equations governing the spatiotemporal evolution of the diffusion front of an excitation mode undergoing diffusion in the system under consideration. The commonly known type of subdiffusion, corresponding to the Mittag-Leffler (or Cole-Cole) relaxation, appears as a special case of the studied anomalous diffusion processes. PMID:21230450

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

    PubMed

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

    2015-12-01

    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). PMID:26458138

  13. Uncovering Implicit Assumptions: a Large-Scale Study on Students' Mental Models of Diffusion

    NASA Astrophysics Data System (ADS)

    Stains, Marilyne; Sevian, Hannah

    2015-12-01

    Students' mental models of diffusion in a gas phase solution were studied through the use of the Structure and Motion of Matter (SAMM) survey. This survey permits identification of categories of ways students think about the structure of the gaseous solute and solvent, the origin of motion of gas particles, and trajectories of solute particles in the gaseous medium. A large sample of data ( N = 423) from students across grade 8 (age 13) through upper-level undergraduate was subjected to a cluster analysis to determine the main mental models present. The cluster analysis resulted in a reduced data set ( N = 308), and then, mental models were ascertained from robust clusters. The mental models that emerged from analysis were triangulated through interview data and characterised according to underlying implicit assumptions that guide and constrain thinking about diffusion of a solute in a gaseous medium. Impacts of students' level of preparation in science and relationships of mental models to science disciplines studied by students were examined. Implications are discussed for the value of this approach to identify typical mental models and the sets of implicit assumptions that constrain them.

  14. Laser soot-scattering imaging of a large buoyant diffusion flame

    SciTech Connect

    Lye, R.C.M.; Toner, S.J.

    1987-01-01

    A novel diagnostic technique, which makes use of laser light scattered by soot particles, was used in an effort to identify the flame sheets within a natural gas diffusion flame. Soot particles, inherently created and consumed in the flame, were used as the scattering medium, which obviated the need for externally supplied seed material. Since no foreign material was added to the flame, the current technique can be considered truly nonintrusive. The soot distribution within a large buoyant natural gas diffusion flame is argued to be a reasonable marker of the flame sheets. Measurements made in 47.4-190 kW natural gas flames stabilized on a 0.5 m diameter burner show that the flame sheets are highly wrinkled and convoluted surfaces. The flame sheets are distributed fairly uniformly within the instantaneous volume of the flame, based on images of the associated soot, and the instantaneous flame volume is devoid of soot for 40-60% of the time. When soot is present, it is observed as thin sheets which become narrower in regions where the average strain rate is estimated to be greater.

  15. Primary Pulmonary Diffuse Large B-Cell Lymphoma on FDG PET/CT-MRI and DWI

    PubMed Central

    Xu, Huiting; Xu, Kai; Wang, Ru; Liu, Xiaohua

    2015-01-01

    Abstract Primary pulmonary diffuse large B-cell lymphoma (PPDLBCL) directly arising from lung tissue is extremely rare. It may usually be misdiagnosed as inflammation including pulmonary tuberculosis, even lung cancer, because its clinical symptoms and signs are often nonspecific. The final diagnosis usually depends on lung biopsy. Herein, we report a case of PPDLBCL and review of diagnosis of this disease, particularly in radiology. A 44-year-old man presented with cough, sputum, and intermittent chest pain for 4 weeks. Multiple radiological examinations showed an irregular mass in the right upper lobe with ground-glass opacities around it and air-filled bronchi in the consolidation. Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography-magnetic resonance imaging (MRI) detected positive FDG uptake, and diffusion-weighted imaging indicated abnormal hyperintension in the lesion. Inflammation was suspected, but malignance cannot be excluded. Finally, ultrasound-guided fine-needle aspiration cytology was performed for histological examination and definitive diagnosis yielded lymphomatous cells infiltration in the right upper lobe. This report emphasizes the significance of multimodality radiological examinations. Multimodality imaging contributes to proper diagnosis, staging, and management of lymphomas. PMID:26200643

  16. Azimuthal diffusion of the large-scale circulation of turbulent Rayleight-Bénard convection

    NASA Astrophysics Data System (ADS)

    He, Xiaozhou; van Gils, Dennis P. M.; Bodenschatz, Eberhard; Ahlers, Guenter

    2015-11-01

    We present measurements of the azimuthal orientation θ0 (t) of the large-scale circulation (LSC) of turbulent Rayleight-Bénard convection. The sample was a cylinder with height and diameter equal to 1.12 m. We used compressed SF6 gas at pressures up to 19 bars as the fluid. The measurements covered the Rayleigh-number range 1012 <= Ra <=1014 at a Prandtl number Pr ~= 0 . 80 . We found that the preferred orientation of the LSC upflow was aligned to the West, consistent with Earth's Coriolis force. The LSC azimuthal dynamics was diffusive, driven by the small-scale turbulent fluctuations. For Ra <=1013 the Reynolds number Reθ˙ based on the azimuthal diffusivity had a Ra dependence similar to that seen for 109 <= Ra <=1011 and Pr = 4 . 38 . The Pr dependence Reθ˙ ~Prα with α ~= - 1 . 2 was the same as that found for the Reynolds number based on the root-mean-square fluctuation velocity in the interior bulk flow. For Ra = Ra1* ~= 2 ×1013 Reθ˙ showed the ultimate-state transition and for Ra >= Ra2* ~= 8 ×1013 it had a Ra dependence with an exponent of 0 . 40 +/- 0 . 02 . Supported by the Max Planck Society, the Volkswagenstiftung, the DFD Sonderforschungsbereich SFB963, and NSF Grant DMR11-58514.

  17. Diffuse large B cell lymphoma of the cranial vault: two case reports.

    PubMed

    Tashiro, Ryosuke; Kanamori, Masayuki; Suzuki, Hiroyoshi; Utsunomiya, Akihiro; Meguro, Kuniaki; Uenohara, Hiroshi; Tominaga, Teiji

    2015-10-01

    Malignant lymphoma of the cranial vault is a rare entity and the tumor growth patterns are not well understood. Here we report two cases of malignant lymphoma involving the scalp and epidural space with slight changes in the intervening skull. A 63-year-old woman presented with a scalp mass in her right frontal area. Computed tomography (CT) and magnetic resonance (MR) imaging demonstrated mass lesions in the scalp and epidural space with slight osteolytic changes in the intervening skull. She underwent resection of the lesions. A 53-year-old man presented with a mass in his right frontal area. CT and MR imaging showed mass lesions in the scalp and epidural space without changes in the skull. He underwent resection of the lesions. The histopathological diagnosis was diffuse large B cell lymphoma in both cases. Microscopic examination of the intervening skull found that the bone marrow was diffusely replaced by lymphoma cells, and lymphoma cells extended to the extra- or intra-cranial space along the emissary veins without destruction of the cortical or trabecular bone. These histopathological findings explain the radiological findings and provide the clues to elucidate the mechanism of extension of cranial vault lymphoma. PMID:26177806

  18. Molecular Classification, Pathway Addiction, and Therapeutic Targeting in Diffuse Large B-cell Lymphoma

    PubMed Central

    Puvvada, Soham; Kendrick, Samantha; Rimsza, Lisa

    2015-01-01

    The rapid emergence of molecularly-based techniques to detect changes in the genetic landscape of diffuse large B-cell lymphoma (DLBCL) including gene expression, DNA and RNA sequencing, and epigenetic profiling, has significantly impacted the understanding and therapeutic targeting of DLBCL. In this review, we will briefly discuss the new methods used in the study of DLBCL. We will describe the influence of the generated data on DLBCL classification and the identification of new entities and altered cell survival strategies with a focus on the renewed interest in some classic oncogenic pathways that are currently targeted for new therapy. Lastly, we will examine the molecular genomic studies that revealed the importance of the tumor microenvironment in the pathogenesis of DLBCL. PMID:24080457

  19. T cells, mast cells and microvascular density in diffuse large B cell lymphoma.

    PubMed

    Marinaccio, Christian; Ingravallo, Giuseppe; Gaudio, Francesco; Perrone, Tommasina; Ruggieri, Simona; Opinto, Giuseppina; Nico, Beatrice; Maiorano, Eugenio; Specchia, Giorgina; Ribatti, Domenico

    2016-08-01

    Diffuse large B cell lymphoma (DLBCL) is recognized as the most common form of non-Hodgkin lymphoma (NHL), accounting for about 40 % of all cases of NHL. Among the cellular components of the tumor inflammatory infiltrate, T cells and mast cells have been demonstrated to be correlated with tumor angiogenesis. In this report, we have investigated CD3 and tryptase expression and their relationship with microvascular density (MVD) in DLBCL patients. Moreover, we determined the significance of CD3 expression in bulky and non-bulky disease. CD3 expression was significantly lower in bulky disease patients when compared to non-bulky ones. CD3 showed a positive correlation with tryptase and MVD, while multiple regression analysis efficaciously predicted MVD depending on CD3 and tryptase as predictors, supporting a complex interplay between these cells in sustaining tumor angiogenesis in DLBCL patients. PMID:25957593

  20. Primary diffuse large B-cell lymphoma of the left ureter: A case report

    PubMed Central

    Chen, Ping; Jiang, Maoqing; Lin, Yuanwei; Ye, Xianwang; Ruan, Xinzhong; Huang, Qiuli

    2016-01-01

    Diffuse large B-cell lymphoma (DLBCL) is a subtype of non-Hodgkin lymphoma occurring in various sites, but rarely involving the ureters. Primary DLBCL is a rare entity. Imaging studies in a 82-year-old male patient revealed left hydronephrosis and an area of nodular soft tissue density in the upper ureteral wall. On enhanced computed tomography scans, the lesion exhibited early enhancement. As the lesion was considered to be malignant, a left nephroureterectomy was performed for the purpose of pathological diagnosis. Histological analysis and immunohistochemistry revealed DLBCL. Since the surgery, the patient has survived for 16 months without evidence of a relapse. Thus, in cases with ureteral stenosis or obstruction for which the cause is uncertain, the possibility of primary lymphoma of the ureter should be considered and further histopathological examination of bioptic samples should be performed as soon as possible. PMID:27588189

  1. Diffusive superconductors beyond the Usadel approximation: Electron-hole asymmetry and large photoelectric effect

    NASA Astrophysics Data System (ADS)

    Kalenkov, Mikhail S.; Zaikin, Andrei D.

    2015-07-01

    We extend the quasiclassical formalism for diffusive superconductors by deriving anisotropic (gradient) corrections to the Usadel equation. We demonstrate that in a number of physical situations such corrections may play a crucial role, being responsible for the effects which cannot be recovered within the standard Usadel approximation. One of them is the so-called photoelectric effect in superconductors and superconducting-normal (SN) hybrid structures. Provided a superconducting part of the system is irradiated by an external ac electromagnetic field, the charge imbalance develops and a nonvanishing dc voltage is induced across the SN interface. In the presence of magnetic impurities in a superconductor the magnitude of this effect becomes large and can easily be detected in modern experiments.

  2. Progress in the Large-Eddy Simulation of an Asymmetric Plane Diffuser

    NASA Technical Reports Server (NTRS)

    Fatica, Massimiliano; Mittal, Rajat

    1996-01-01

    The flow through a plane asymmetric diffuser is a good test case for assessing the capability of LES since it contains features such as large scale unsteady separation and strong intermittency which are difficult to capture using conventional modeling approaches. Previous attempts to simulate this flow (Kaltenbach, 1994) have significantly underpredicted the extent of separation. The objective of the present research is to understand why the previous simulations did not predict the flow separation correctly. This study focuses on mesh refinement and matching of the inlet velocity profile. In order to perform this study, the flow solver of Kaltenbach (1994) was modified to increase its accuracy and efficiency. The improved algorithm allows for better resolution at affordable CPU cost.

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

    PubMed

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

    2010-11-01

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

  4. [Diffuse large B-cell lymphoma developed newly after 9-year remission of a follicular lymphoma].

    PubMed

    Hirano, Taichi; Tsuji, Takahiro; Yamasaki, Hiroshi; Toyozumi, Yasuo; Arima, Nobuyuki; Tsuda, Hiroyuki

    2016-02-01

    Follicular lymphoma (FL) occasionally transforms into diffuse large B-cell lymphoma (DLBCL). This is generally associated with a poor prognosis, necessitating more potent chemotherapy as salvage treatment. However, de novo DLBCL, but not DLBCL transformed from FL, can be treated as primary DLBCL. We encountered a 63-year-old woman who developed DLBCL after a 9-year remission following treatment of FL. To differentiate DLBCL transformed from FL and de novo DLBCL, VDJ gene rearrangements in IgH were examined by PCR using biopsy specimens from both lymphomas. The results revealed the two lymphomas to be different clones. Thus, she was diagnosed with primary DLBCL. Therefore, routine chemotherapy and radiation therapy were conducted for the primary DLBCL with a limited stage, achieving complete remission. Treatment based on the clonality assessment of VDJ gene rearrangements is potentially useful for treating late relapse of B-cell lymphoma according to the pathological conditions of patients. PMID:26935635

  5. Clinical impact of molecular features in diffuse large B-cell lymphoma and follicular lymphoma.

    PubMed

    Pon, Julia R; Marra, Marco A

    2016-01-14

    Our understanding of the pathogenesis and heterogeneity of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) has been dramatically enhanced by recent attempts to profile molecular features of these lymphomas. In this article, we discuss ways in which testing for molecular features may impact DLBCL and FL management if clinical trials are designed to incorporate such tests. Specifically, we discuss how distinguishing lymphomas on the basis of cell-of-origin subtypes or the presence of other molecular features is prognostically and therapeutically significant. Conversely, we discuss how the molecular similarities of DLBCL and FL have provided insight into the potential of both DLBCL and FL cases to respond to agents targeting alterations they have in common. Through these examples, we demonstrate how the translation of our understanding of cancer biology into improvements in patient outcomes depends on analyzing the molecular correlates of treatment outcomes in clinical trials and in routinely treated patients. PMID:26447189

  6. Large Eddy Simulation Of Gravitational Effects In Transitional And Turbulent Gas-Jet Diffusion Flames

    NASA Technical Reports Server (NTRS)

    Jaberi, Farhad A.; Givi, Peyman

    2003-01-01

    The influence of gravity on the spatial and the compositional structures of transitional and turbulent hydrocarbon diffusion flames are studies via large eddy simulation (LES) and direct numerical simulation (DNS) of round and planar jets. The subgrid-scale (SGS) closures in LES are based on the filtered mass density function (FMDF) methodology. The FMDF represents the joint probability density function (PDF) of the SGS scalars, and is obtained by solving its transport equation. The fundamental advantage of LES/FMDF is that it accounts for the effects of chemical reaction and buoyancy exactly. The methodology is employed for capturing some of the fundamental influences of gravity in equilibrium flames via realistic chemical kinetic schemes. Some preliminary investigation of the gravity effects in non-equilibrium flames is also conducted, but with idealized chemical kinetics models.

  7. Primary Gastrointestinal Diffuse Large B Cell Lymphoma Presenting with Cold Agglutinin Disease

    PubMed Central

    Eskazan, Ahmet Emre; Akmurad, Hamida; Ongoren, Seniz; Ozer, Ozden; Ferhanoglu, Burhan

    2011-01-01

    Cold agglutinin disease (CAD) is an autoimmune hemolytic anemia (AIHA) generally caused by IgM autoantibodies which exhibit maximal reactivity at 4°C. CAD can be idiopathic or secondary to some diseases and/or conditions. Only a minority of cases of secondary AIHA in non-Hodgkin's lymphoma (NHL) are associated with cold antibodies. Diffuse large B cell lymphoma (DLBCL) is the most common subtype of NHLs with a proportion of nearly 30% of all adult cases. 40% of patients with DLBCL have an extranodal disease or at least disease initially confined to extranodal sites. The most common extranodal site is the gastrointestinal tract. We present a patient with primary gastrointestinal DLBCL who presented with CAD and was treated with a CHOP-Rituximab regimen. PMID:21887126

  8. New insights into MicroRNAs involves in drug resistance in diffuse large B cell lymphoma

    PubMed Central

    Yu, Xin; Li, Zheng

    2015-01-01

    Diffuse large B cell lymphoma (DLBCL) accounts for nearly 40% of non-Hodgkin’s lymphoma cases. The combined chemotherapy of rituximab, cyclophosphamide, Adriamycin, vincristine, and prednisone (R-CHOP) is considered as the standard therapy for DLBCL; however, nearly half of the patients become refractory to the R-CHOP regimen. Early identification of drug resistance and therapeutic failures are crucial for the identification of high-risk patients. MicroRNAs (miRNAs) are a group of small and non-coding RNAs negatively regulating gene expression through binding to their target mRNAs. Recent studies demonstrated that miRNAs are involved in chemotherapeutic drug resistance in tumor. In our review, we summarize the current evidence on the role of miRNAs in the prediction and modulation of cellular response to rituximab, cyclophosphamide, Adriamycin, vincristine, and prednisone in DLBCL. PMID:26885255

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

    PubMed Central

    Carbone, Mario; Della Ferrera, Francesco; Carbone, Lucio; Gatti, Gaia; Carrozzo, Marco

    2014-01-01

    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. PMID:25580308

  10. A prospective study of the LMB regimen for diffuse large cell non Hodgkin's lymphoma in adults.

    PubMed

    Voog, E; Sebban, C; Biron, P; Philip, T; Blay, J Y

    2000-02-01

    Although the CHOP regimen remains a standard first line chemotherapy for diffuse large cell lymphoma (DLCL) in adults, a majority of these patients will still experience disease progression after the completion of this treatment. The LMB protocol is an intensive chemotherapy regimen which yields high survival rates in Burkitt's lymphoma (BL) and diffuse large cell lymphoma (DLCL) in children, as well as in primary cerebral DLCL (PCL) of adults. Here, we report the long term results of this regimen in a prospective series of 22 adult patients with DLCL excluding PCL. Fifteen male and 7 female patients with a median age of 30 years (range: 20-55) were treated prospectively between 1988 and 1993. 16 (72%) patients had an age adjusted International Pronostic Index (IPI) > or = 1. The median duration of the treatment was 15 weeks (range 13-19). Nineteen of the 22 patients (87%) experienced an objective response (14 complete, and 5 partial responses) at the end of the protocol. The predominant toxicity was myelosuppression: 89% of the COPADEM courses were followed by grade IV neutropenia and 5% with grade IV infection. One patient died (4%) of treatment related toxicity. With a median follow-up of 94 months and a minimum follow-up of 65 months, 8-year overall and progression-free survival are 73% and 67% respectively. The 8 year overall survival were 100%, 78% and 42% in patients with an IPI 0, 1, and 2-3 respectively. This short intensive regimen yields promising long term survival rates in this monocentric prospective study and may deserve to be tested in a larger multicentric prospective study comparing it to the CHOP regimen. PMID:10784397

  11. Detection and outcome of occult leptomeningeal disease in diffuse large B-cell lymphoma and Burkitt lymphoma

    PubMed Central

    Wilson, Wyndham H.; Bromberg, Jacoline E.C.; Stetler-Stevenson, Maryalice; Steinberg, Seth M.; Martin-Martin, Lourdes; Muñiz, Carmen; Sancho, Juan Manuel; Caballero, Maria Dolores; Davidis, Marjan A.; Brooimans, Rik A.; Sanchez-Gonzalez, Blanca; Salar, Antonio; González-Barca, Eva; Ribera, Jose Maria; Shovlin, Margaret; Filie, Armando; Dunleavy, Kieron; Mehrling, Thomas; Spina, Michele; Orfao, Alberto

    2014-01-01

    The benefit of intrathecal therapy and systemic rituximab on the outcome of diffuse large B-cell lymphoma at risk of central nervous system disease is controversial. Furthermore, the effect of intrathecal treatment and rituximab in diffuse large B-cell and Burkitt lymphoma with occult leptomeningeal disease detected by flow cytometry at diagnosis is unknown. Untreated diffuse large B-cell (n=246) and Burkitt (n=80) lymphoma at clinical risk of central nervous system disease and having had pre-treatment cerebrospinal fluid were analyzed by flow cytometry and cytology. Spinal fluid involvement was detected by flow cytometry alone (occult) in 33 (13%) diffuse large B-cell and 9 (11%) Burkitt lymphoma patients, and detected by cytology in 11 (4.5%) and 5 (6%) patients, respectively. Diffuse large B-cell lymphoma with occult spinal fluid involvement had poorer survival (P=0.0001) and freedom from central nervous system relapse (P<0.0001) compared to negative cases. Burkitt lymphoma with occult spinal fluid involvement had an inferior freedom from central nervous system relapse (P=0.026) but not survival. The amount of intrathecal chemotherapy was quantitatively associated with survival in diffuse large B-cell lymphoma with (P=0.02) and without (P=0.001) occult spinal fluid involvement. However, progression of systemic disease and not control of central nervous system disease was the principal cause of treatment failure. In diffuse large B-cell lymphoma, systemic rituximab was associated with improved freedom from central nervous system relapse (P=0.003) but not with survival. Our results suggest that patients at risk of central nervous system disease should be evaluated by flow cytometry and that intrathecal prophylaxis/therapy is beneficial. PMID:24727817

  12. Brief Report: Role of Thymic Reconstitution in the Outcome of AIDS-Related PML.

    PubMed

    Chalkias, Spyridon G; Gheuens, Sarah; Bord, Evelyn; Batson, Stephanie; Koralnik, Igor J

    2015-12-01

    Implications of thymopoiesis in AIDS-related opportunistic infections remain unexplored. We used progressive multifocal leukoencephalopathy (PML), caused by JC virus (JCV), as an opportunistic infection model, and we simultaneously investigated thymic output and T-cell responses against JCV in 22 patients with PML treated with combined antiretroviral therapy. Thymic output was significantly associated with JCV-specific CD4⁺ and CD8⁺ T-cell responses and improved survival. Our data suggest that patients with AIDS-related PML and impaired thymopoiesis are less likely to develop a robust JCV-specific cellular immune response and consequently are at an increased risk for a poor clinical outcome. PMID:26181821

  13. Diffuse pionic gamma-ray emission from large-scale structures in the Fermi era

    SciTech Connect

    Dobardžić, A.; Prodanović, T. E-mail: prodanvc@df.uns.ac.rs

    2014-02-20

    For more than a decade now, the complete origin of the diffuse gamma-ray emission background (EGRB) has been unknown. Major components like unresolved star-forming galaxies (making ≲ 50% of the EGRB) and blazars (≲ 23%), have failed to explain the entire background observed by Fermi. Another, though subdominant, contribution is expected to come from the process of large-scale structure formation. The growth of structures is accompanied by accretion and merger shocks, which would, with at least some magnetic field present, give rise to a population of structure-formation cosmic rays (SFCRs). Though expected, this cosmic-ray population is still hypothetical and only very weak limits have been placed to their contribution to the EGRB. The most promising insight into SFCRs was expected to come from Fermi-LAT observations of clusters of galaxies, however, only upper limits and no detection have been placed. Here, we build a model of gamma-ray emission from large-scale accretion shocks implementing a source evolution calibrated with the Fermi-LAT cluster observation limits. Though our limits to the SFCR gamma-ray emission are weak (above the observed EGRB) in some cases, in others, some of our models can provide a good fit to the observed EGRB. More importantly, we show that these large-scale shocks could still give an important contribution to the EGRB, especially at high energies. Future detections of cluster gamma-ray emission would help place tighter constraints on our models and give us a better insight into large-scale shocks forming around them.

  14. Rituximab in the treatment of diffuse large B-cell lymphoma primary of the lung.

    PubMed

    Aviles, Agustin; Nambo, Maria J; Huerta-Guzman, Judith; Silva, Luis; Neri, Natividad

    2013-03-01

    Diffuse large B-cell lymphoma primary of lung (DLBCL-PL) is a rare presentation of extranodal lymphoma, in most cases chemotherapy-based anthracyclines: CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) has been the treatment, with excellent outcome. The addition of rituximab to CHOP (R-CHOP) has been considered the gold standard in the treatment of nodal DLBCL. Thus, we assess in a large number of cases of DLBCL-PL whether the use of R-CHOP could improve survival in this setting of patients. Forty-two patients with DLBCL-PL, stage IE, age 65 years or younger, were treated with standard R-CHOP, no consolidation radiotherapy or maintenance therapy were considered. They were matched with patients who received CHOP alone to assess efficacy and toxicity. Complete response was observed in 35 patients (83%), and 7 patients were considered failure (16%). The study has a median follow-up of 42.8 months. Actuarial curves at 5 years showed that progression-free survival was 88 % and overall survival was 70 %. The results were not statistically different when compared retrospectively with patients who received CHOP alone. Treatment was well tolerated. The addition of rituximab to chemotherapy did not improve outcome in patients with DLBCL-PL. PMID:23394581

  15. Superdense core mode in the Large Helical Device with an internal diffusion barrier

    SciTech Connect

    Morisaki, T.; Ohyabu, N.; Masuzaki, S.; Kobayashi, M.; Sakamoto, R.; Miyazawa, J.; Funaba, H.; Ida, K.; Ikeda, K.; Kaneko, O.; Morita, S.; Mutoh, S.; Nagaoka, K.; Nagayama, Y.; Nakajima, N.; Narihara, K.; Oka, Y.; Osakabe, M.; Peterson, B. J.; Sakakibara, S.

    2007-05-15

    In reduced recycling discharges using a local island divertor in the Large Helical Device [O. Motojima, H. Yamada, A. Komori et al., Phys. Plasmas 6, 1843 (1999)], a stable high-density plasma develops in the core region when a series of pellets is injected. A core region with {approx}5x10{sup 20} m{sup -3} and temperature of 0.85 keV is maintained by an internal diffusion barrier (IDB). The density gradient at the IDB (r/a{approx}0.6) is very high, and the particle confinement time in the core region is {approx}0.4 s. Because of the increase in the central pressure, a large Shafranov shift up to {approx}0.3 m is observed. The critical ingredients for IDB formation are a strongly pumped divertor to reduce edge recycling, and multiple pellet injection to ensure efficient central fueling. No serious magnetohydrodynamics activity and impurity accumulation have been observed so far in this improved discharge.

  16. Predicting AIDS-related events using CD4 percentage or CD4 absolute counts

    PubMed Central

    Pirzada, Yasmin; Khuder, Sadik; Donabedian, Haig

    2006-01-01

    Background The extent of immunosuppression and the probability of developing an AIDS-related complication in HIV-infected people is usually measured by the absolute number of CD4 positive T-cells. The percentage of CD4 positive cells is a more easily measured and less variable number. We analyzed sequential CD4 and CD8 numbers, percentages and ratios in 218 of our HIV infected patients to determine the most reliable predictor of an AIDS-related event. Results The CD4 percentage was an unsurpassed predictor of the occurrence of AIDS-related events when all subsets of patients are considered. The CD4 absolute count was the next most reliable, followed by the ratio of CD4/CD8 percentages. The value of CD4 percentage over the CD4 absolute count was seen even after the introduction of highly effective HIV therapy. Conclusion The CD4 percentage is unsurpassed as a parameter for predicting the onset of HIV-related diseases. The extra time and expense of measuring the CD4 absolute count may be unnecessary. PMID:16916461

  17. AIDS-Related Factors Predictive of Suicidal Ideation of Low and High Intent among Gay and Bisexual Men.

    ERIC Educational Resources Information Center

    Schneider, Stephen G.; And Others

    1991-01-01

    Studied Acquired Immune Deficiency Syndrome (AIDS)-related stressors and suicidal ideation/intent among 778 gay and bisexual men (none with AIDS). Compared to those who reported no suicidal ideation over past six months, those who reported ideation (n=212) were more likely to report recent bereavement of partner, AIDS-Related Disorder (ARC)…

  18. Primary diffuse large B-cell lymphoma of the central nervous system: A case report and literature review

    PubMed Central

    CHEN, DAWEI; GU, WEIHONG; LI, WENZHONG; LIU, XIAOLIANG; YANG, XIAOYU

    2016-01-01

    The present study reports the clinical diagnosis and management of a patient with primary diffuse large B-cell lymphoma (Bcl) of the central nervous system (CNS). Making an early diagnosis of primary diffuse large Bcl is challenging due to the variable and complicated clinical manifestations of the disease. The relevant literature was reviewed, and high-dose methotrexate, whole brain radiotherapy and highly active antiretroviral therapy was recommended for the patient. The present study elucidates the role of positron emission tomography-computed tomography scans for the diagnosis and management of primary diffuse large Bcl of the CNS, and demonstrates the importance of resection surgery in the management of the disease. Specifically, the present study proposes that resection surgery may be applied in the early stages of disease for patients with a single occupied lesion and increased intracranial pressure. PMID:27123068

  19. PIM kinases are progression markers and emerging therapeutic targets in diffuse large B-cell lymphoma

    PubMed Central

    Brault, L; Menter, T; Obermann, E C; Knapp, S; Thommen, S; Schwaller, J; Tzankov, A

    2012-01-01

    Background: PIM serine/threonine kinases are often highly expressed in haematological malignancies. We have shown that PIM inhibitors reduced the survival and migration of leukaemic cells. Here, we investigated PIM kinases in diffuse large B-cell lymphoma (DLBCL) biopsy samples and DLBCL cell lines. Methods: Immunohistochemical staining for PIM kinases and CXCR4 was performed on tissue microarrays from a cohort of 101 DLBCL cases, and the effects of PIM inhibitors on the survival and migration of DLBCL cell lines were determined. Results: PIM1 expression significantly correlated with the activation of signal transducer and activator of transcription (STAT) 3 and 5, P-glycoprotein expression, CXCR4-S339 phosphorylation, and cell proliferation. Whereas most cases exhibited cytoplasmic or cytoplasmic and nuclear PIM1 and PIM2 expression, 12 cases (10 of the non-germinal centre DLBCL type) expressed PIM1 predominately in the nucleus. Interestingly, nuclear expression of PIM1 significantly correlated with disease stage. Exposure of DLBCL cell lines to PIM inhibitors modestly impaired cellular proliferation and CXCR4-mediated migration. Conclusion: This work demonstrates that PIM expression in DLBCL is associated with activation of the JAK/STAT signalling pathway and with the proliferative activity. The correlation of nuclear PIM1 expression with disease stage and the modest response to small-molecule inhibitors suggests that PIM kinases are progression markers rather than primary therapeutic targets in DLBCL. PMID:22722314

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

    PubMed

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

    2016-07-14

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

  1. Improving outcomes for patients with diffuse large B-cell lymphoma.

    PubMed

    Flowers, Christopher R; Sinha, Rajni; Vose, Julie M

    2010-01-01

    Diffuse large B-cell lymphoma (DLBCL) is the most commonly occurring form of non-Hodgkin lymphoma in the western world. Until the mid 1990s the incidence of DLBCL increased in both sexes, across racial categories, and across all age groups except the very young, the etiology of most cases remains unknown. DLBCL is associated with an aggressive natural history, but it can be cured with combination chemotherapy regimens like cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), which has been the mainstay of therapy for several decades. Remarkable progress has been made in understanding the biological heterogeneity of DLBCL and in improving survival for DLBCL patients with novel combinations of chemotherapy and immunotherapy. Gene expression profiling (GEP) has uncovered DLBCL subtypes that have distinct clinical behaviors and prognoses, and the addition of the monoclonal antibody, rituximab, to CHOP has markedly improved outcomes. Future approaches to DLBCL management will use molecular signatures identified through GEP to provide prognostic information and to isolate therapeutic targets that are being evaluated for DLBCL patients who relapse or those with high risk disease. PMID:21030533

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

    PubMed

    Sancho, Juan-Manuel; Ribera, Josep-Maria

    2016-01-15

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

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

    PubMed

    Gorodetskiy, Vadim; Klapper, Wolfram; Probatova, Natalya; Vasilyev, Vladimir

    2016-01-01

    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. PMID:26998372

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

    PubMed

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

    2016-04-01

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

  5. Clinical characteristics and prognostic analysis of Chinese patients with diffuse large B-cell lymphoma.

    PubMed

    Ke, Xiaoyan; Wang, Jing; Gao, Zifen; Zhao, Lingzhi; Li, Min; Jing, Hongmei; Wang, Jijun; Zhao, Wei; Gilbert, Heather; Yang, Xiao-Feng

    2010-01-15

    Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma in adults. As it is a highly heterogenous disease, many studies have focused on finding useful prognostic factors to help guide therapy. In this report, we examine several biological markers in 83 patients with DLBCL enrolled in our hospital, including cell origin, serum lactate dehydrogenase (LDH) levels, and international prognostic index (IPI), in order to find the best combination of prognostic factors. We also examined whether DLBCL has a significant geographic difference, since several studies have suggested that the prevalence and potential etiological factors of lymphomas in China may be different from those in other countries. Our results demonstrate that: (1) patients in China have higher extranodal tissue involvement and different extranodal organ distribution than patients reported from other countries; (2) Chinese patients have higher rates of germinal center (GC) cell origin; and (3) among nine prognostic variables, lower IPI scores, GC cell origin determined by immunohistochemical staining, and no more than 1.5 times of normal levels of LDH are statistically significant good prognostic factors in Chinese patients with DLBCL, whereas age at the time of diagnosis, clinical stage, beta(2)-microglobulin levels, extranodal tissue involvement, and expression levels of Bcl-6 protein were not useful in determining prognosis. PMID:19819170

  6. ACR Appropriateness Criteria® Diffuse Large B-Cell Lymphoma.

    PubMed

    Dabaja, Bouthaina S; Advani, Ranjana; Hodgson, David C; Dhakal, Sughosh; Flowers, Christopher R; Ha, Chul S; Hoppe, Bradford S; Mendenhall, Nancy P; Metzger, Monika L; Plastaras, John P; Roberts, Kenneth B; Shapiro, Ronald; Smith, Sonali M; Terezakis, Stephanie A; Winkfield, Karen M; Younes, Anas; Constine, Louis S

    2015-12-01

    The management of diffuse large B-cell lymphoma depends on the initial diagnosis including molecular and immunophenotypic characteristics, Ann Arbor staging, and International Prognostic Index (IPI score). Treatment approaches with different chemotherapy regimens used is discussed in detail. The role of radiation as a consolidation is discussed including: (1) the prerituximab randomized trials that challenged the role of radiation, (2) recent prospective studies (UNFOLDER/RICOVER-60), and (3) retrospective studies; the last 2 showed a potential benefit of radiation both for early and advanced stage. The document also discusses the role of positron emission tomography/computed tomography for predicting outcome and potentially guiding therapy. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. PMID:26583344

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

    PubMed Central

    Rüetschi, Ulla; Stenson, Martin; Hasselblom, Sverker; Nilsson-Ehle, Herman; Hansson, Ulrika; Fagman, Henrik; Andersson, Per-Ola

    2015-01-01

    Diffuse large B-cell lymphoma (DLBCL), the most common lymphoma, is a heterogeneous disease where the outcome for patients with early relapse or refractory disease is very poor, even in the era of immunochemotherapy. In order to describe possible differences in global protein expression and network patterns, we performed a SILAC-based shotgun (LC-MS/MS) quantitative proteomic analysis in fresh-frozen tumor tissue from two groups of DLBCL patients with totally different clinical outcome: (i) early relapsed or refractory and (ii) long-term progression-free patients. We could identify over 3,500 proteins; more than 1,300 were quantified in all patients and 87 were significantly differentially expressed. By functional annotation analysis on the 66 proteins overexpressed in the progression-free patient group, we found an enrichment of proteins involved in the regulation and organization of the actin cytoskeleton. Also, five proteins from actin cytoskeleton regulation, applied in a supervised regression analysis, could discriminate the two patient groups. In conclusion, SILAC-based shotgun quantitative proteomic analysis appears to be a powerful tool to explore the proteome in DLBCL tumor tissue. Also, as progression-free patients had a higher expression of proteins involved in the actin cytoskeleton protein network, such a pattern indicates a functional role in the sustained response to immunochemotherapy. PMID:26060582

  8. DNA repair genes are selectively mutated in diffuse large B cell lymphomas

    PubMed Central

    de Miranda, Noel FCC; Peng, Roujun; Georgiou, Konstantinos; Wu, Chenglin; Sörqvist, Elin Falk; Berglund, Mattias; Chen, Longyun; Gao, Zhibo; Lagerstedt, Kristina; Lisboa, Susana; Roos, Fredrik; van Wezel, Tom; Teixeira, Manuel R.; Rosenquist, Richard; Sundström, Christer; Enblad, Gunilla; Nilsson, Mats; Zeng, Yixin; Kipling, David

    2013-01-01

    DNA repair mechanisms are fundamental for B cell development, which relies on the somatic diversification of the immunoglobulin genes by V(D)J recombination, somatic hypermutation, and class switch recombination. Their failure is postulated to promote genomic instability and malignant transformation in B cells. By performing targeted sequencing of 73 key DNA repair genes in 29 B cell lymphoma samples, somatic and germline mutations were identified in various DNA repair pathways, mainly in diffuse large B cell lymphomas (DLBCLs). Mutations in mismatch repair genes (EXO1, MSH2, and MSH6) were associated with microsatellite instability, increased number of somatic insertions/deletions, and altered mutation signatures in tumors. Somatic mutations in nonhomologous end-joining (NHEJ) genes (DCLRE1C/ARTEMIS, PRKDC/DNA-PKcs, XRCC5/KU80, and XRCC6/KU70) were identified in four DLBCL tumors and cytogenetic analyses revealed that translocations involving the immunoglobulin-heavy chain locus occurred exclusively in NHEJ-mutated samples. The novel mutation targets, CHEK2 and PARP1, were further screened in expanded DLBCL cohorts, and somatic as well as novel and rare germline mutations were identified in 8 and 5% of analyzed tumors, respectively. By correlating defects in a subset of DNA damage response and repair genes with genomic instability events in tumors, we propose that these genes play a role in DLBCL lymphomagenesis. PMID:23960188

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

    PubMed

    Bret, Caroline; Klein, Bernard; Moreaux, Jérôme

    2012-12-01

    Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma and displays heterogeneous clinical and molecular characteristics. In this study, high throughput gene expression profiling of DLBCL tumor samples was used to design a 12-gene expression-based risk score (GERS) predictive for patient's overall survival. GERS allowed identifying a high-risk group comprising 46,4% of the DLBCL patients in two independent cohorts (n=414 and n=69). GERS was shown to be an independent predictor of survival when compared to the previously published prognostic factors, including the International Prognostic Index (IPI). GERS displayed a prognostic value in germinal-center B-cell-like subgroup (GCB) and activated B cell-like (ABC) molecular subgroups of patients as well as in DLBCL patients treated with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) or rituximab-CHOP (R-CHOP) regimens. Combination of GERS and IPI lead to a potent prognostic classification of DLBCL patients. Finally, a genomic instability gene signature was highlighted in gene expression profiles of patients belonging to the high-risk GERS-defined group. PMID:23482333

  10. [Expression and clinical significance of Ki-67 in diffuse large B cell lymphoma].

    PubMed

    Zhou, Ying; Zhao, Yu; Bo, Jian; Li, Yan-Fen; Ma, Chao; Shi, Ya-Nan

    2013-10-01

    This study was aimed to evaluate the proliferation-associated antigen Ki-67 expression in diffuse large B cell lymphoma (DLBCL) and its clinical significance. The Ki-67 expression and its correlation with prognosis in 50 patients with DLBCL treated with rituximab plus CHOP (R-CHOP) between January 2008 and December 2010 were analyzed retrospectively. The results indicated that there was no significant relationship between Ki-67 expression and clinical features, including age, sex, staging, B symptoms, LDH level, IPI, extranodal site involvement, presence of bulky tumors (>10 cm in diameter), bone marrow involvement, GCG nor GCB type, or response to first line treatment. The median survival was 50 months and 15 months in low Ki-67 expression group (<85%) and in high Ki-67 expression group ( ≥ 85%) respectively. The overall survival (OS) and progress-free survival (PFS) in low Ki-67 expression group were obviously longer than that in high Ki-67 expression group (P = 0.001; P = 0.027). In univariate analysis, the clinical factors associated with OS included Ann Arbor staging and Ki-67 expression. The clinical factors associated with PFS included Ann Arbor staging. IPI and Ki-67 expression. In multivariate analysis. The Ki-67 expression level was an independent prognostic factor for OS (HR = 4.90; 95% CI, 1.456-16.511; P = 0.0103). It is concluded that Ki-67 expression level seems to be an effective marker for evaluation of DLBCL prognosis. PMID:24156426

  11. Noninvasive monitoring of diffuse large B-cell lymphoma by immunoglobulin high-throughput sequencing.

    PubMed

    Kurtz, David M; Green, Michael R; Bratman, Scott V; Scherer, Florian; Liu, Chih Long; Kunder, Christian A; Takahashi, Kazuhiro; Glover, Cynthia; Keane, Colm; Kihira, Shingo; Visser, Brendan; Callahan, Jason; Kong, Katherine A; Faham, Malek; Corbelli, Karen S; Miklos, David; Advani, Ranjana H; Levy, Ronald; Hicks, Rodney J; Hertzberg, Mark; Ohgami, Robert S; Gandhi, Maher K; Diehn, Maximilian; Alizadeh, Ash A

    2015-06-11

    Recent studies have shown limited utility of routine surveillance imaging for diffuse large B-cell lymphoma (DLBCL) patients achieving remission. Detection of molecular disease by immunoglobulin high-throughput sequencing (Ig-HTS) from peripheral blood provides an alternate strategy for surveillance. We prospectively evaluated the utility of Ig-HTS within 311 blood and 105 tumor samples from 75 patients with DLBCL, comparing Ig-HTS from the cellular (circulating leukocytes) and acellular (plasma cell-free DNA) compartments of peripheral blood to clinical outcomes and (18)fluoro-deoxyglucose positron emission tomography combined with computed tomography (PET/CT; n = 173). Clonotypic immunoglobulin rearrangements were detected in 83% of patients with adequate tumor samples to enable subsequent monitoring in peripheral blood. Molecular disease measured from plasma, compared with circulating leukocytes, was more abundant and better correlated with radiographic disease burden. Before treatment, molecular disease was detected in the plasma of 82% of patients compared with 71% in circulating cells (P = .68). However, molecular disease was detected significantly more frequently in the plasma at time of relapse (100% vs 30%; P = .001). Detection of molecular disease in the plasma often preceded PET/CT detection of relapse in patients initially achieving remission. During surveillance time points before relapse, plasma Ig-HTS demonstrated improved specificity (100% vs 56%, P < .0001) and similar sensitivity (31% vs 55%, P = .4) compared with PET/CT. Given its high specificity, Ig-HTS from plasma has potential clinical utility for surveillance after complete remission. PMID:25887775

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

    PubMed

    Sarkozy, Clémentine; Coiffier, Bertrand

    2013-04-01

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

  13. Targeting netrin-1/DCC interaction in diffuse large B-cell and mantle cell lymphomas.

    PubMed

    Broutier, Laura; Creveaux, Marion; Vial, Jonathan; Tortereau, Antonin; Delcros, Jean-Guy; Chazot, Guillaume; McCarron, Mark J; Léon, Sophie; Pangault, Céline; Gadot, Nicolas; Colombe, Amélie; Boulland, Marie-Laure; Blachier, Jonathan; Marie, Julien C; Traverse-Glehen, Alexandra; Donzé, Olivier; Chassagne-Clément, Catherine; Salles, Gilles; Tarte, Karin; Mehlen, Patrick; Castets, Marie

    2016-02-01

    DCC (Deleted in Colorectal Carcinoma) has been demonstrated to constrain tumor progression by inducing apoptosis unless engaged by its ligand netrin-1. This has been shown in breast and colorectal cancers; however, this tumor suppressive function in other cancers is not established. Using a transgenic mouse model, we report here that inhibition of DCC-induced apoptosis is associated with lymphomagenesis. In human diffuse large B-cell lymphoma (DLBCL), an imbalance of the netrin-1/DCC ratio suggests a loss of DCC-induced apoptosis, either via a decrease in DCC expression in germinal center subtype or by up-regulation of netrin-1 in activated B-cell (ABC) one. Such imbalance is also observed in mantle cell lymphoma (MCL). Using a netrin-1 interfering antibody, we demonstrate both in vitro and in vivo that netrin-1 acts as a survival factor for ABC-DLBCL and MCL tumor cells. Together, these data suggest that interference with the netrin-1/DCC interaction could represent a promising therapeutic strategy in netrin-1-positive DLBCL and MCL. PMID:26882243

  14. Diffuse large B-cell lymphoma presenting in the leukemic phase

    PubMed Central

    Pires, Patricia Puccetti; Rays, Jairo; Catania, Marcos; Lima, Fabiana Roberto; Noronha, Thiago Rodrigo; Abdo, Andre Neder Ramires; Pereira, Juliana

    2016-01-01

    Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma comprising a heterogeneous group of disorders with variable histological and clinical behavior. Although other lymphomas may present in the leukemic phase more frequently, this appearance is unusually observed among DLBCL cases. Diagnosing lymphoma is not always easy, and the patient's clinical status quite often may hamper invasive procedures for diagnosis pushing the clinician to look for alternatives to reach the nearest possible accurate diagnosis. The authors report the case of a middle-aged man who presented the history of malaise, weight loss, and low-grade fever. The peripheral blood count showed leukocytosis with the presence of blasts and thrombocytopenia. The cytological morphology and immunophenotyping of the peripheral blood and bone marrow aspirate, as well as the bone marrow biopsy accompanied by a thorough immunohistochemical analysis, rendered the diagnosis of DLBCL in the leukemic phase. The patient was prescribed R-CHOP with a favorable outcome. Intra-abdominal lymph node biopsy was avoided because of the patient's critical medical condition. The authors highlight this rare form of presentation of DLBCL as well as the combination of peripheral blood, bone marrow aspirate, and bone marrow biopsy for reaching the diagnosis in cases were a lymph node sample is unavailable for the diagnostic work-up. PMID:27284540

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

    PubMed

    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. PMID:27096423

  16. MicroRNA and gene networks in human diffuse large B-cell lymphoma.

    PubMed

    Wang, Kunhao; Xu, Zhiwen; Wang, Ning; Xu, Ting; Zhu, Minghui

    2014-11-01

    Molecular biologists have collected considerable data regarding the involvement of genes and microRNAs (miRNAs) in cancer. However the underlying mechanisms of cancer with regard to genes and miRNAs remain unclear. The aim of the present study was to evaluate diffuse large B-cell lymphoma (DLBCL) and construct regulatory networks of genes and miRNAs to gradually reveal the underlying mechanisms of DLBCL development. The first differential expression network that is presented is an experimentally validated network of miRNAs and genes. This network presents known biological regulatory associations among miRNAs and genes in the human body. The second network is a DLBCL differential expression network. Differentially expressed gene and miRNA data regarding DLBCL were collected and, based on the first network and the differentially expressed data, the second network was inferred, which demonstrates the irregular regulatory associations that may lead to the occurrence of DLBCL. The third network is a DLBCL-associated network. This network is comprised of non-differentially expressed genes and miRNAs that contribute to numerous DLBCL processes. The similarities and differences among the three networks were extracted and compared to distinguish key regulatory associations; furthermore, important signaling pathways in DLBCL were identified. The present study partially clarified the pathogenesis of DLBCL and provided an improved understanding of the underlying molecular mechanisms, as well as a potential treatment for DLBCL. PMID:25289101

  17. Differentiating Between Burkitt Lymphoma and CD10+ Diffuse Large B-Cell Lymphoma

    PubMed Central

    McGowan, Paul; Nelles, Nicole; Wimmer, Jana; Williams, Dawn; Wen, Jianguo; Li, Marilyn; Ewton, April; Curry, Choladda; Zu, Youli; Sheehan, Andrea; Chang, Chung-Che (Jeff)

    2016-01-01

    The goal of this study was to evaluate routine flow cytometric (FC) immunophenotypic markers in differentiating between Burkitt lymphoma (BL) and CD10+ diffuse large B-cell lymphoma (DLBCL). We performed retrospective analysis of FC data from 55 patients. We evaluated 9 FC parameters: forward and side scatter (FSC and SSC); mean fluorescent intensity (MFI) for CD20, CD10, CD38, CD79b, CD43, and CD71; and the percentage of neoplastic cells positive for CD71 (%CD71). The FSC; MFIs of CD10, CD43, CD79b, and CD71; and %CD71 cells were significantly different between BL and CD10+ DLBCL (P < .05; Student t test). A 5-point scoring system (FSC, %CD71, and MFIs of CD43, CD79b, and CD71) was devised, and 6 (60%) of 10 BLs scored 3 or greater and 1 (10%) of 10 CD10+ DLBCLs scored 3 (P = .04; χ2). Our findings indicate that routine FC parameters can aid in differentiating BL from CD10+ DLBCL. PMID:22431545

  18. Maintenance therapy with interferon alfa 2b in patients with diffuse large cell lymphoma.

    PubMed

    Avilés, A; Díaz-Maqueo, J C; García, E L; Talavera, A; Guzmán, R

    1992-11-01

    Forty-eight consecutive patients with diffuse large cell lymphoma (DLCL) in complete remission (CR) after conventional chemotherapy were enrolled in a prospective clinical trial. The maintenance therapy was a random either nothing or interferon alfa 2b (IFN) 5.0 MU three times a week for one year. The median duration of CR in the patients treated with IFN has not been reached. After five years 60% of patients remain in CR compared to the control group who had a median CR of 40 months (p < 0.001). Actuarial five-years survival in the IFN treated patients was 88% compared to 42% in the control group (p < 0.001). Maintenance therapy with IFN has been beneficial in patients with DLCL with improvement of duration of CR and survival without the excessive toxicity of most common third generation regimen chemotherapy. We felt that IFN could be explored in most controlled clinical trials in patients with DLCL in CR after conventional chemotherapy. PMID:1487412

  19. Diffuse Large B-Cell Lymphoma of Maxilla – A Case Report of Late Relapse

    PubMed Central

    Kumar, Medikonda Suresh; Chandragiri, Anuradha; Amarnath, Konda

    2016-01-01

    Diffuse Large B Cell Lymphomas (DLBCL) encompasses a heterogeneous group of tumors that together constitute the commonest of all Non Hodgkin Lymphoma (NHL) and the proclivity of DLBCL to oral cavity is unknown. They mostly arise from soft tissues as asymptomatic lesions, mostly without ‘B’ symptoms and involvement of jaw bones is uncommon. Most studies and case reports of oral DLBCL’s are based on, manifestation of primary extra-nodal disease or a component of a disseminated disease process involving regional lymph nodes. Many investigators have proposed that patients with this cell type who maintain a complete response for 24 consecutive months are cured because late relapses seldom occur. With advances in treatment modalities, many patients with NHL become long-term survivors and the risk of relapses or second tumors are of growing concern. We present a case of DLBCL which relapsed after five years of initial lesion in a 41 year old female patient and presented as a nonspecific bilateral anterior maxillary radiolucency. DLBCL usually express pan-B markers with small percentage expressing T-cell markers. Few rare cases of DLBCL have shown CD3 expression, which is a most sensitive T-cell marker which was focally expressed in the present case. PMID:27190967

  20. Sequential transcription factor targeting for diffuse large B-cell lymphomas

    PubMed Central

    Cerchietti, Leandro C; Polo, Jose M; Da Silva, Gustavo F; Farinha, Pedro; Shaknovich, Rita; Gascoyne, Randy D; Dowdy, Steven F; Melnick, Ari

    2009-01-01

    Transcription factors play a central role in malignant transformation by activating or repressing waves of downstream target genes. Therapeutic targeting of transcription factors can reprogram cancer cells to lose their advantages in growth and survival. The BCL6 transcriptional repressor plays a central role in the pathogenesis of diffuse large B-cell lymphomas (DLBCLs) and controls downstream checkpoints including the p53 tumor suppressor gene. We report that a specific inhibitor of BCL6 called BPI can trigger a p53 response in DLBCL cells. This was partially due to induction of p53 activity and partially due to relief of direct repression by BCL6 of p53 target genes. BPI could thus induce a p53-like response even in the presence of mutant p53. Moreover, sequential BCL6 peptide inhibitors followed by p53 peptide or small molecule activators provided a more powerful anti-lymphoma effect than either treatment alone by maximally restoring p53 target gene expression. Therefore, tandem targeting of the overlapping BCL6 and p53 transcriptional programs can correct aberrant survival pathways in DLBCL and might provide an effective therapeutic approach to lymphoma therapy. PMID:18451163

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

    PubMed

    Barrington, Sally F; Mikhaeel, N George

    2016-06-01

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

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

    PubMed

    Gergely, Lajos; Illés, Árpád

    2016-07-01

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

  3. Diffuse large B-cell lymphoma involving the central nervous system.

    PubMed

    Gualco, Gabriela; Weiss, Lawrence M; Barber, Glen N; Bacchi, Carlos E

    2011-02-01

    Lymphomas involving the central nervous system are recognized increasingly in immunocompetent as well as immunosuppressed individuals, and the majority of the cases are diffuse large B-cell lymphoma (DLBCL). The aim of this study was to compare the immunophenotype, clinicopathological features, and association with Epstein-Barr virus (EBV) of DLBCL of the central nervous system (CNS) in 3 different clinical situations: primary, in immunocompetent patients; "primary," in immunosuppressed patients; and in patients with secondary involvement by systemic lymphoma. The authors reviewed the clinicopathological features, morphology, immunophenotype (according to germinal-center B-cell-like and nongerminal B-cell-like subtypes), and association with EBV in 36 cases of DLBCL of the CNS, including 25 primary cases, 5 associated with immunosuppression, and 6 cases with secondary involvement. Survival was evaluated in 15 cases of primary CNS lymphomas. Of the 36 patients, 19 were male and 18 female. Only 2 cases of lymphomas were EBV-positive; both occurred in immunosuppressed patients. Separation into germinal-center and non-germinal center subtypes by an immunohistochemistry panel showed that 68% of primary, 80% of secondary, and 83% of the cases associated with immunosuppression were of non-germinal-center subtype, respectively. Patients with non-germinal-center immunophenotype showed significantly worse survival than those with CNS lymphomas of the germinal-center subtype. PMID:21087986

  4. Identification of LMO2 transcriptome and interactome in diffuse large B-cell lymphoma

    PubMed Central

    Cubedo, Elena; Gentles, Andrew J.; Huang, Chuanxin; Natkunam, Yasodha; Bhatt, Shruti; Lu, Xiaoqing; Jiang, Xiaoyu; Romero-Camarero, Isabel; Freud, Aharon; Zhao, Shuchun; Bacchi, Carlos E.; Martínez-Climent, Jose A.; Sánchez-García, Isidro; Melnick, Ari

    2012-01-01

    LMO2 regulates gene expression by facilitating the formation of multipartite DNA-binding complexes. In B cells, LMO2 is specifically up-regulated in the germinal center (GC) and is expressed in GC-derived non-Hodgkin lymphomas. LMO2 is one of the most powerful prognostic indicators in diffuse large B-cell (DLBCL) patients. However, its function in GC B cells and DLBCL is currently unknown. In this study, we characterized the LMO2 transcriptome and transcriptional complex in DLBCL cells. LMO2 regulates genes implicated in kinetochore function, chromosome assembly, and mitosis. Overexpression of LMO2 in DLBCL cell lines results in centrosome amplification. In DLBCL, the LMO2 complex contains some of the traditional partners, such as LDB1, E2A, HEB, Lyl1, ETO2, and SP1, but not TAL1 or GATA proteins. Furthermore, we identified novel LMO2 interacting partners: ELK1, nuclear factor of activated T-cells (NFATc1), and lymphoid enhancer-binding factor1 (LEF1) proteins. Reporter assays revealed that LMO2 increases transcriptional activity of NFATc1 and decreases transcriptional activity of LEF1 proteins. Overall, our studies identified a novel LMO2 transcriptome and interactome in DLBCL and provides a platform for future elucidation of LMO2 function in GC B cells and DLBCL pathogenesis. PMID:22517897

  5. Role of Rituximab and Rituximab Biosimilars in Diffuse Large B-Cell Lymphoma.

    PubMed

    Coleman, Morton; Lammers, Philip E; Ciceri, Fabio; Jacobs, Ira A

    2016-04-01

    Diffuse large B-cell lymphoma (DLBCL), an aggressive non-Hodgkin lymphoma (NHL), is the most-common subtype of NHL. DLBCL can be classified into at least 3 major immunologically distinct types, which contributes to considerable variation in disease prognosis and response to treatment. DLBCL potentially is curable, even when diagnosed at advanced stages. The current standard of care for most patients with untreated or relapsed/refractory DLBCL is chemoimmunotherapy containing rituximab, an anti-CD20 monoclonal antibody. With advanced understanding of the molecular mechanisms involved in the pathogenesis of DLBCL and specific signaling pathways that are activated in different subtypes, potential new therapeutic targets have been identified, some of which are at the late stages of clinical development. This review summarizes the critical role of rituximab in the current standard of care treatment for DLBCL and discusses why rituximab is likely to remain an important component of treatment options for DLBCL in the foreseeable future. In addition, current and emerging therapeutic agents, including potential benefits of rituximab biosimilars, for patients with DLBCL are discussed. The advent of rituximab biosimilars may facilitate accessibility of rituximab-based chemotherapies to patients with DLBCL and has potential cost-saving benefits for healthcare systems globally. PMID:26906106

  6. SOCS1 Mutation Subtypes Predict Divergent Outcomes in Diffuse Large B-Cell Lymphoma (DLBCL) Patients

    PubMed Central

    Kohler, Christian W.; Bentink, Stefan; Kreuz, Markus; Melzner, Ingo; Ritz, Olga; Trümper, Lorenz; Loeffler, Markus; Spang, Rainer; Möller, Peter

    2013-01-01

    Suppressor of cytokine signaling 1 (SOCS1) is frequently mutated in primary mediastinal and diffuse large B-cell lymphomas (DLBCL). Currently, the prognostic relevance of these mutations in DLBCL is unknown. To evaluate the value of the SOCS1 mutation status as a prognostic biomarker in DLBCL patients, we performed full-length SOCS1 sequencing in tumors of 154 comprehensively characterized DLBCL patients. We identified 90 SOCS1 mutations in 16% of lymphomas. With respect to molecular consequences of mutations, we defined two distinct subtypes: those with truncating (major) and those with non-truncating mutations (minor), respectively. The SOCS1 mutated subgroup or the minor/major subtypes cannot be predicted on clinical grounds; however, assignment of four established gene-expression profile-based classifiers revealed significant associations of SOCS1 major cases with germinal center and specific pathway activation pattern signatures. Above all, SOCS1 major cases have an excellent overall survival, even better than the GCB-like subgroup. SOCS1 minor cases had a dismal survival, even worse than the ABC gene signature group. The SOCS1 mutation subsets retained prognostic significance in uni- and multivariate analyses. Together our data indicate that assessment of the SOCS1 mutation status is a single gene prognostic biomarker in DLBCL. PMID:23296022

  7. Pharmacoproteomics identifies combinatorial therapy targets for diffuse large B cell lymphoma

    PubMed Central

    Goldstein, Rebecca L.; Yang, Shao Ning; Taldone, Tony; Chang, Betty; Gerecitano, John; Elenitoba-Johnson, Kojo; Shaknovich, Rita; Tam, Wayne; Leonard, John P.; Chiosis, Gabriela; Cerchietti, Leandro; Melnick, Ari

    2015-01-01

    Rationally designed combinations of targeted therapies for refractory cancers, such as activated B cell–like diffuse large B cell lymphoma (ABC DLBCL), are likely required to achieve potent, durable responses. Here, we used a pharmacoproteomics approach to map the interactome of a tumor-enriched isoform of HSP90 (teHSP90). Specifically, we chemically precipitated teHSP90-client complexes from DLBCL cell lines with the small molecule PU-H71 and found that components of the proximal B cell receptor (BCR) signalosome were enriched within teHSP90 complexes. Functional assays revealed that teHSP90 facilitates BCR signaling dynamics by enabling phosphorylation of key BCR signalosome components, including the kinases SYK and BTK. Consequently, treatment of BCR-dependent ABC DLBCL cells with PU-H71 attenuated BCR signaling, calcium flux, and NF-κB signaling, ultimately leading to growth arrest. Combined exposure of ABC DLBCL cell lines to PU-H71 and ibrutinib, a BCR pathway inhibitor, more potently suppressed BCR signaling than either drug alone. Correspondingly, PU-H71 combined with ibrutinib induced synergistic killing of lymphoma cell lines, primary human lymphoma specimens ex vivo, and lymphoma xenografts in vivo, without notable toxicity. Together, our results demonstrate that a pharmacoproteome-driven rational combination therapy has potential to provide more potent BCR-directed therapy for ABC DLCBL patients. PMID:26529251

  8. Cerebellar EBV-associated diffuse large B cell lymphoma following angioimmunoblastic T cell lymphoma

    PubMed Central

    Zhou, Yi; Rosenblum, Marc K.; Dogan, Ahmet; Jungbluth, Achim A.; Chiu, April

    2016-01-01

    Epstein-Barr virus (EBV)-associated B cell lymphoproliferative disorders may be seen in patients with angioimmunoblastic T cell lymphoma (AITL). Although both nodal and extranodal sites of involvement have been described, central nervous system involvement by B cell lymphoma following AITL has not previously been documented. We report a first example of such unusual presentation, in which an 80-year-old man developed diffuse large B cell lymphoma (DLBCL) in the cerebellum 4 months after the initial diagnosis of AITL. EBV-encoded RNAs were detected in the DLBCL, suggesting that EBV played a pivotal role in the pathogenesis of high-grade histologic progression of AITL. The patient survived less than 9 months after his initial diagnosis of AITL. We believe that this case expands the spectrum of extranodal manifestation of EBV-positive B cell lymphoma associated with AITL and illustrates the importance of recognition of this association when encountering unusual central nervous system lesions in patients with known AITL.

  9. A large scale height galactic component of the diffuse 2-60 keV background

    NASA Technical Reports Server (NTRS)

    Iwan, D.; Marshall, F. E.; Boldt, E. A.; Mushotzky, R.; Shafer, R. A.; Stottlemyer, A.

    1982-01-01

    The diffuse 2-60 keV X-ray background has a galactic component clearly detectable by its strong variation with both galactic latitude and longitude. This galactic component is typically 10 percent of the extragalactic background toward the galactic center, half that strong toward the anticenter, and extrapolated to a few percent of the extragalactic background toward the galactic poles. It is acceptably modeled by a finite radius emission disk with a scale height of several kiloparsecs. The averaged galactic spectrum is best fitted by a thermal spectrum of kT about 9 keV, a spectrum much softer than the about 40 keV spectrum of the extragalactic component. The most likely source of this emission is low luminosity stars with large scale heights such as subdwarfs. Inverse Compton emission from GeV electrons on the microwave background contributes only a fraction of the galactic component unless the local cosmic ray electron spectrum and intensity are atypical.

  10. The potential relevance of the endocannabinoid, 2-arachidonoylglycerol, in diffuse large B-cell lymphoma

    PubMed Central

    Zhang, Jianqing; Medina-Cleghorn, Daniel; Bernal-Mizrachi, Leon; Bracci, Paige M.; Hubbard, Alan; Conde, Lucia; Riby, Jacques; Nomura, Daniel K.; Skibola, Christine F.

    2016-01-01

    Diffuse large B-cell lymphoma is an aggressive, genetically heterogenerous disease and the most common type of non-Hodgkin lymphoma among adults. To gain further insights into the etiology of DLBCL and to discover potential disease-related factors, we performed a serum lipid analysis on a subset of individuals from a population-based NHL case-control study. An untargeted mass-spectrometry-based metabolomics platform was used to analyze serum samples from 100 DLBCL patients and 100 healthy matched controls. Significantly elevated levels of the endocannabinoid, 2-arachidonoylglycerol (2-AG), were detected in the serum of DLBCL patients (121%, P < 0.05). In the male controls, elevated 2-AG levels were observed in those who were overweight (BMI ≥ 25 - < 30 kg/m2; 108%, P < 0.01) and obese (BMI ≥ 30 kg/m2; 118%, P < 0.001) compared to those with a BMI < 25 kg/m2. DLBCL cell lines treated with exogenous 2-AG across a range of concentrations, exhibited heterogenous responses: proliferation rates were markedly higher in 4 cell lines by 22%-68% (P < 0.001) and lower in 8 by 20%-75% (P < 0.001). The combined findings of elevated 2-AG levels in DLBCL patients and the proliferative effects of 2-AG on a subset of DLBCL cell lines suggests that 2-AG may play a potential role in the pathogenesis or progression of a subset of DLBCLs. PMID:26973858

  11. Multi-contrast large deformation diffeomorphic metric mapping for diffusion tensor imaging

    PubMed Central

    Ceritoglu, Can; Oishi, Kenichi; Li, Xin; Chou, Ming-Chung; Younes, Laurent; Albert, Marilyn; Lyketsos, Constantine; van Zijl, Peter C.M.; Miller, Michael I.; Mori, Susumu

    2010-01-01

    Diffusion tensor imaging (DTI) can reveal detailed white matter anatomy and has the potential to detect abnormalities in specific white matter structures. Such detection and quantification are, however, not straightforward. The voxel-based analysis after image normalization is one of the most widely used methods for quantitative image analyses. To apply this approach to DTI, it is important to examine if structures in the white matter are well registered among subjects, which would be highly dependent on employed algorithms for normalization. In this paper, we evaluate the accuracy of normalization of DTI data using a highly elastic transformation algorithm, called large deformation diffeomorphic metric mapping. After simulation-based validation of the algorithm, DTI data from normal subjects were used to measure the registration accuracy. To examine the impact of morphological abnormalities on the accuracy, the algorithm was also tested using data from Alzheimer’s disease (AD) patients with severe brain atrophy. The accuracy level was measured by using manual landmark-based white matter matching and surface-based brain and ventricle matching as gold standard. To improve the accuracy level, cascading and multi-contrast approaches were developed. The accuracy level for the white matter was 1.88 ± 0.55 and 2.19 ± 0.84 mm for the measured locations in the controls and patients, respectively. PMID:19398016

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

    PubMed Central

    Gorodetskiy, Vadim; Klapper, Wolfram; Probatova, Natalya; Vasilyev, Vladimir

    2016-01-01

    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. PMID:26998372

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

    PubMed

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

    2016-06-01

    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. PMID:26699656

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

    PubMed

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

    2010-03-01

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

  15. Productive human immunodeficiency virus infection levels correlate with AIDS-related manifestations in the patient

    SciTech Connect

    Mathez, D.; Paul, D.; de Belilovsky, C.; Sultan, Y.; Deleuze, J.; Gorin, I.; Saurin, W.; Decker, R.; Leibowitch, J. )

    1990-10-01

    Mononuclear cells were obtained from 71 human immunodeficiency virus type 1 (HIV-1) seropositive subjects presenting and first visit either as asymptomatic or with minor symptoms and with CD4 lymphocytes greater than 550 per mm3 (group A, 35 patients) or as patients with AIDS, AIDS-related illnesses, or CD4 lymphocytes less than 400 per mm3 (group B, 36 patients). After 1-5 years of follow-up, 13 patients of group A had essentially retained their initial status (asymptomatics); the 22 others had suffered clinical or immunological deterioration (progressors). Frozen cells were thawed and submitted to lethal gamma-irradiation in vitro (4500 rads; 1 rad = 0.01 Gy) before they were cultured with normal phytohemagglutinin-stimulated lymphocytes to determine radiation-resistant HIV expression ex vivo (R-HEV). HIV antigenemia correlated with R-HEV values in 142 samples (r = 0.92, P less than 0.001) but was a less sensitive predictor of disease than R-HEV. R-HEV was detected in all specimens from patients with major AIDS-related illnesses or HIV-associated CD4 lymphopenia. In 77% of the progressors from group A, R-HEV detection preceded the onset of AIDS-associated disease or CD4 lymphopenia by 1 year (average). Conversely, R-HEV was low or was not detected in 36 sequential specimens from the 13 patients who remained asymptomatic over the following 2-5 years. Thus, persistently low HIV expression in vivo predicted a nondiseased state, whereas higher HIV expression levels seemed necessary for disease to occur. These data indicate that R-HEV is related to productive HIV infection in vivo, the latter acting as a determinant of AIDS-related illnesses. In view of this, measurement of HIV expression levels in the patient should be useful in antiviral efficacy trials.

  16. AIDS-related knowledge, attitudes, and behaviors among juvenile delinquents in Israel.

    PubMed

    Slonim-Nevo, V

    Fifty-six Israeli adolescents under the care of probation officers were interviewed about their AIDS-related knowledge, attitudes, and behaviors. The results suggest that these adolescents put themselves at risk of HIV infection. A substantial proportion of the sample demonstrated a lack of knowledge on issues relevant for AIDS prevention. The majority held negative attitudes toward condoms but were also sexually active, and some had experienced unprotected sexual intercourse, anal sex, and drug use. Most of the respondents, moreover, showed a lack of competence in handling situations that pressure them to act unsafely. Implications for practice are discussed. PMID:1343361

  17. Akt Inhibitor MK2206 in Treating Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma

    ClinicalTrials.gov

    2015-07-31

    Adult Grade III Lymphomatoid Granulomatosis; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Secondary Central Nervous System Non-Hodgkin Lymphoma; Small Intestinal Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenstrom Macroglobulinemia

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

    Cancer.gov

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

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

    NASA Technical Reports Server (NTRS)

    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.

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

    Sun, Yao; Joks, Monika; Xu, Li-Ming; Chen, Xiu-Li; Qian, Dong; You, Jin-Qiang; Yuan, Zhi-Yong

    2016-01-01

    Background The breast is a rare site of extranodal involvement of diffuse large B-cell lymphoma (DLBCL). We aimed to assess the clinical characteristics, prognostic factors, and treatment outcomes of breast DLBCL. Patients and methods We retrospectively analyzed 113 patients (from our institution and the literature) between 1973 and 2014. The primary end point was overall survival (OS). Kaplan–Meier OS curves were compared with the log-rank test. Cox regression analysis was applied to determine the prognostic factors for OS, progression-free survival (PFS), local control (LC), and cause-specific survival (CSS). Results A total of 113 patients were included in the study: 42 cases from our hospital and 71 cases from 12 publications. The median age at diagnosis was 58 years. With a median follow-up time of 39.2 months, the estimated 5-year OS, PFS, LC, and CSS were 71.4%, 58.8%, 75.6%, and 74.9%, respectively. In multivariate analysis, more than four cycles of chemotherapy, having localized cancer, lumpectomy with or without axillary lymph node (ALN) dissection, and low to low-to-intermediate International Prognostic Index were favorable factors for OS. For PFS, significant prognostic factors were rituximab use, B symptoms, and tumor size. As for the local group, lumpectomy with or without ALN dissection and more than four cycles of chemotherapy were favorable factors for OS. Tumor size >4 cm and nonuse of rituximab were adverse factors for PFS. Twenty-one patients (18.6%) developed local relapse and 33 (29.2%) developed systemic relapse. Eight patients had central nervous system relapse (7.3%). Conclusion Our results reveal that local and extended staging criteria can reflect the different prognosis and treatment outcomes of breast DLBCL. Rituximab use, lumpectomy, and more than four cycles of chemotherapy are recommended as a treatment regimen. However, further study is warranted to validate our data. PMID:27103833

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

    PubMed

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

    2015-12-01

    Sarcopenia reportedly predicts poor outcomes in elderly patients with diffuse large B-cell lymphoma (DLBCL). However, because previous studies only involved elderly patients, it is difficult to generalize these results to all patients with DLBCL. We retrospectively analyzed 207 patients with DLBCL who received the R-CHOP or R-THP-COP regimen between June 2004 and May 2014. Sarcopenia was measured by the analysis of CT images at the L3 level before treatment. The surface of muscular tissues was selected according to the CT Hounsfield unit. This value was normalized for stature in order to calculate the L3 skeletal muscle index (L3 SMI, cm(2)/m(2)). Median age at diagnosis in the 121 males and 86 females was 67 years (range, 19-86 years). The sex-specific cutoffs for the L3 SMI were determined by receiver operator curve (ROC) analysis. Sarcopenic patients were older than non-sarcopenic patients, with a median age of 70 and 65 years, respectively (p < 0.001). Other International Prognostic Index factors were not significantly different when comparing sarcopenic and non-sarcopenic patients. With a median follow-up of 50.4 months, the 3-year overall survival (OS) was 70 % in the sarcopenic group and 85 % in the non-sarcopenic group (p = 0.0260). In a subgroup analysis by gender, there was a significant difference in the OS when comparing sarcopenic and non-sarcopenic patients in males but not in females (p = 0.0003, p = 0.4440, respectively). Sarcopenia is an independent prognostic factor in male patients with DLBCL. PMID:26385388

  3. Expression of D-type cyclins in mantle cell and diffuse large B-cell lymphomas.

    PubMed

    Zlamalikova, Lenka; Moulis, Mojmir; Salek, David; Jarkovsky, Jiri; Smarda, Jan; Smardova, Jana

    2016-05-01

    D-type cyclins are involved in cell cycle regulation and play an important role in the pathogenesis of lymphomas. Aberrant expression of cyclin D1 is associated with mantle cell lymphoma (MCL) and serves as a diagnostic marker of MCL. Analysis of cyclin D expression in tumor tissues of patients with diffuse large B-cell lymphoma (DLBCL) which comprises a heterogeneous group of tumors may contribute to their stratification. We analyzed expression of cyclin D1, D2, and D3 mRNAs in 30 MCL and 104 DLBCL patients using qRT-PCR and addressed their significance for disease outcome. We confirmed a high level of cyclin D1 mRNA in 29 MCL cases (97%). One case (3%) was identified as positive for cyclin D2. Expression of cyclin D1 was limited to MCL and did not occur in DLBCL. Overexpression of cyclin D2, which is rare in MCL, occurred more frequently in DLBCL (11 cases, 10.6%). We showed that high expression of cyclin D2 in DLBCL cases de novo decreased the overall survival rate (P=0.016) and progression-free survival (P=0.009). The expression pattern of cyclin D3 was similar in both types of studied lymphomas and it did not affect the disease outcome. PMID:26985765

  4. Prognostic and Clinicopathological Value of Survivin in Diffuse Large B-cell Lymphoma

    PubMed Central

    Zhang, Ya; Wang, Jianhong; Sui, Xiaohui; Li, Ying; Lu, Kang; Fang, Xiaosheng; Jiang, Yujie; Wang, Xin

    2015-01-01

    Abstract Up to date, survivin, a well-known inhibitor of apoptosis, has attracted considerable attention as a potential biomarker and therapeutic target in diffuse large B-cell lymphoma (DLBCL). Nevertheless, there still remains no consensus on heterogeneous results. Herein, a meta-analysis was performed to clarify a convincing significance of survivin status on prognosis and clinicopathology of DLBCL patients. Eligible studies were identified by searching Medline, Embase, Scopus, CNKI, and Wanfang databases (last updated on November 30, 2014). Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Heterogeneity and sensitivity were also analyzed. Moreover, Begg, Egger test, and funnel plots were applied to evaluate the publication bias. We finally included 17 eligible studies with the total number of 1352 patients in the meta-analysis. The pooled results showed that positive survivin expression in DLBCL was associated with inferior overall survival (OS) (HR: 1.880, 95% CI: 1.550–2.270) in patients. Moreover, a significant association was revealed between survivin expression and advanced clinical stage (III + IV) (OR: 0.611, 95% CI: 0.452–0.827), higher International Prognosis Index (IPI) score (Score 3–5) (OR: 0.559; 95% CI: 0.410–0.761), elevated serum lactic dehydrogenase (LDH) (OR: 0.607, 95% CI: 0.444–0.831), presence of bone marrow involvement (OR: 2.127, 95% CI: 1.154–3.921) together with reduced complete remission (CR) rate (OR: 0.478, 95% CI: 0.345–0.662). The results suggest that survivin could be a useful prognostic biomarker, and a promising target for DLBCL therapeutic intervention. Considering limited HR data adjusted for standard prognostic variables could be retrieved, future high-quality studies will be needed in evaluating the independent prognostic value of survivin expression in DLBCL. PMID:26356696

  5. ON THE FERMI LARGE AREA TELESCOPE SURPLUS OF DIFFUSE GALACTIC GAMMA-RAY EMISSION

    SciTech Connect

    Völk, H. J.; Berezhko, E. G.

    2013-11-10

    Recent observations of diffuse Galactic γ-ray emission (DGE) by the Fermi Large Area Telescope (Fermi-LAT) have shown significant deviations, above a few GeV to about 100 GeV, from DGE models that use the GALPROP code for the propagation of cosmic ray (CR) particles outside their sources in the Galaxy and their interaction with the target distributions of the interstellar gas and radiation fields. The surplus of radiation observed is most pronounced in the inner Galaxy, where the concentration of CR sources is strongest. The present study investigates this 'Fermi-LAT Galactic Plane Surplus' by estimating the γ-ray emission from the sources themselves, which is disregarded in the above DGE models. It is shown that the expected hard spectrum of CRs, still confined in their sources (source cosmic rays, SCRs), can indeed explain this surplus. The method is based on earlier studies regarding the so-called EGRET GeV excess, which by now is generally interpreted as an instrumental effect. The contribution from SCRs is also predicted to increasingly exceed the DGE models above 100 GeV, up to γ-ray energies of about 10 TeV, where the corresponding surplus exceeds the hadronic part of the DGE by about one order of magnitude. Above such energies, the emission surplus should decrease again with energy due to the finite lifetime of the assumed supernova remnant sources. Observations of the DGE in the inner Galaxy at 15 TeV with the ground-based Milagro γ-ray detector and, at TeV energies, with the ARGO-YBJ detector are interpreted to provide confirmation of a significant SCR contribution to the DGE.

  6. HLA-G and MHC Class II Protein Expression in Diffuse Large B-Cell Lymphoma.

    PubMed

    Jesionek-Kupnicka, Dorota; Bojo, Marcin; Prochorec-Sobieszek, Monika; Szumera-Ciećkiewicz, Anna; Jabłońska, Joanna; Kalinka-Warzocha, Ewa; Kordek, Radzisław; Młynarski, Wojciech; Robak, Tadeusz; Warzocha, Krzysztof; Lech-Maranda, Ewa

    2016-06-01

    The expression of human leukocyte antigen-G (HLA-G) and HLA class II protein was studied by immunohistochemical staining of lymph nodes from 148 patients with diffuse large B-cell lymphoma (DLBCL) and related to the clinical course of the disease. Negative HLA-G expression was associated with a lower probability of achieving a complete remission (p = 0.04). Patients with negative HLA-G expression tended towards a lower 3-year overall survival (OS) rate compared to those with positive expression of HLA-G (p = 0.08). When restricting the analysis to patients receiving chemotherapy with rituximab, the estimated 3-year OS rate of patients with positive HLA-G expression was 73.3 % compared with 47.5 % (p = 0.03) in those with negative expression. Patients with negative HLA class II expression presented a lower 3-year OS rate compared to subjects with positive expression (p = 0.04). The loss of HLA class II expression (p = 0.05) and belonging to the intermediate high/high IPI risk group (p = 0.001) independently increased the risk of death. HLA class II expression also retained its prognostic value in patients receiving rituximab; the 3-year OS rate was 65.3 % in patients with positive HLA class II expression versus 29.6 % (p = 0.04) in subjects that had loss of HLA class II expression. To our knowledge, for the first time, the expression of HLA-G protein in DLBCL and its association with the clinical course of the disease was demonstrated. Moreover, the link between losing HLA class II protein expression and poor survival of patients treated with immunochemotherapy was confirmed. PMID:26667793

  7. Prognostic factors for diffuse large B-cell lymphoma in the R(X)CHOP era

    PubMed Central

    Vaidya, R.; Witzig, T. E.

    2014-01-01

    Background The introduction of rituximab (R) to conventional CHOP chemotherapy for newly diagnosed diffuse large B-cell lymphoma (DLBCL) led to an unequivocal improvement in survival, establishing RCHOP as the standard of care. Still, nearly 40% of DLBCL patients will eventually die of relapsed disease. Efforts to improve outcomes by addition of new biologic agents (X) to the RCHOP backbone are underway. In this era of R(X)CHOP, it is imperative to develop prognostic and predictive markers, not only to identify patients who will suffer a particularly aggressive course, but also to accurately select patients for clinical trials from which they will most benefit. Design The following review was undertaken to describe prognostic factors in DLBCL, with emphasis on markers that are accurate, relatively available, and clinically applicable in 2014. Results The International Prognostic Index retains its validity in the era of RCHOP, although with limited ability to predict those with <50% chance of long-term survival. Gene expression profiling has provided novel insights into the biology of DLBCL and led to the development of immunohistochemistry (IHC) algorithms that are in routine practice. Identification of a ‘double-hit’ (DH) lymphoma by fluorescent in situ hybridization with aberrations involving MYC and/or BCL2 and BCL6 genes has important implications due to its extremely dismal prognosis with RCHOP. Other markers such as the absolute lymphocyte count (ALC), serum immunoglobulin free light chains, vitamin D levels, serum cytokines/chemokines, and imaging with positron emission tomography (PET) have all shown promise as future predictive/prognostic tests. Conclusions The future for new treatment options in DLBCL is promising with current clinical trials testing novel targeted agents such as bortezomib, lenalidomide, and ibrutinib as the ‘X’ in R(X)CHOP. Predictive factors are required to select and randomize patients appropriately for these trials. We

  8. The NOTCH pathway is recurrently mutated in diffuse large B-cell lymphoma associated with hepatitis C virus infection

    PubMed Central

    Arcaini, Luca; Rossi, Davide; Lucioni, Marco; Nicola, Marta; Bruscaggin, Alessio; Fiaccadori, Valeria; Riboni, Roberta; Ramponi, Antonio; Ferretti, Virginia V.; Cresta, Stefania; Casaluci, Gloria Margiotta; Bonfichi, Maurizio; Gotti, Manuel; Merli, Michele; Maffi, Aldo; Arra, Mariarosa; Varettoni, Marzia; Rattotti, Sara; Morello, Lucia; Guerrera, Maria Luisa; Sciarra, Roberta; Gaidano, Gianluca; Cazzola, Mario; Paulli, Marco

    2015-01-01

    Hepatitis C virus has been found to be associated with B-cell non-Hodgkin lymphomas, mostly marginal zone lymphomas and diffuse large B-cell lymphoma. Deregulation of signaling pathways involved in normal marginal zone development (NOTCH pathway, NF-κB, and BCR signaling) has been demonstrated in splenic marginal zone lymphoma. We studied mutations of NOTCH pathway signaling in 46 patients with hepatitis C virus-positive diffuse large B-cell lymphoma and in 64 patients with diffuse large B-cell lymphoma unrelated to HCV. NOTCH2 mutations were detected in 9 of 46 (20%) hepatitis C virus-positive patients, and NOTCH1 mutations in 2 of 46 (4%). By contrast, only one of 64 HCV-negative patients had a NOTCH1 or NOTCH2 mutation. The frequency of the NOTCH pathway lesions was significantly higher in hepatitis C virus-positive patients (P=0.002). The 5-year overall survival was 27% (95%CI: 5%–56%) for hepatitis C virus-positive diffuse large B-cell lymphoma patients carrying a NOTCH pathway mutation versus 62% (95%CI: 42%–77%) for those without these genetic lesions. By univariate analysis, age over 60 years, NOTCH2 mutation, and any mutation of the NOTCH pathway (NOTCH2, NOTCH1, SPEN) were associated with shorter overall survival. Mutation of the NOTCH pathway retained an independent significance (P=0.029). In conclusion, a subset of patients with hepatitis C virus-positive diffuse large B-cell lymphoma displays a molecular signature of splenic marginal zone and has a worse clinical outcome. PMID:25381127

  9. Economic empowerment and AIDS-related stigma in rural Kenya: a double-edged sword?

    PubMed

    Gnauck, Katherine; Ruiz, Jamie; Kellett, Nicole; Sussman, Andrew; Sullivan, Mary Ann; Montoya, Maria; Levin, Nick; Tomedi, Angelo; Mwanthi, Mutuku A

    2013-01-01

    Economic empowerment, HIV risk and AIDS-related stigma appear intricately intertwined for women in Kenya. Their interaction must be understood in order to implement effective economic interventions that also decrease HIV risk and stigma. We conducted a qualitative study amongst women in a rural Kamba-speaking community of southeastern Kenya to pursue whether engagement in an economic empowerment initiative (a basket weaving cooperative) influences women's perspectives and experiences with HIV risk and AIDS-related stigma. We conducted seven women's focus groups: participants in the local basket-weaving cooperative comprised four focus groups and non-participants comprised the remaining three groups. The HIV status of the women was not known. Three dominant themes emerged from the focus groups: empowerment, pervasive vulnerability and unanticipated social paradoxes. Contradictions found in these themes suggest that economic empowerment can become a double-edged sword. Economic empowerment enhanced perceived individual, domestic and social community status. However, this enhancement was not protective of domestic violence and perceived HIV risk. Social perceptions may have paradoxically contributed barriers to HIV testing and treatment putting women at greater HIV risk. In conclusion, economic empowerment initiatives for women in developing countries in the context of the HIV epidemic should be coupled with peer mediated support and HIV-risk education. PMID:23668536

  10. HIV and AIDS-related stigma and discrimination: a conceptual framework and implications for action.

    PubMed

    Parker, Richard; Aggleton, Peter

    2003-07-01

    Internationally, there has been a recent resurgence of interest in HIV and AIDS-related stigma and discrimination, triggered at least in part by growing recognition that negative social responses to the epidemic remain pervasive even in seriously affected communities. Yet, rarely are existing notions of stigma and discrimination interrogated for their conceptual adequacy and their usefulness in leading to the design of effective programmes and interventions. Taking as its starting point, the classic formulation of stigma as a 'significantly discrediting' attribute, but moving beyond this to conceptualize stigma and stigmatization as intimately linked to the reproduction of social difference, this paper offers a new framework by which to understand HIV and AIDS-related stigma and its effects. It so doing, it highlights the manner in which stigma feeds upon, strengthens and reproduces existing inequalities of class, race, gender and sexuality. It highlights the limitations of individualistic modes of stigma alleviation and calls instead for new programmatic approaches in which the resistance of stigmatized individuals and communities is utilized as a resource for social change. PMID:12753813

  11. Large Thermal Diffusivity Database Reveals a New Mechanism for Heat Transport in Geomaterials: Diffusion of IR-Polaritons Substantially Augments Phonon-Phonon Scattering

    NASA Astrophysics Data System (ADS)

    Branlund, J. M.; Hofmeister, A.; Dong, J.

    2013-12-01

    Over the course of several years, we have measured heat transport to high temperatures for a large number (ca. 200) of minerals, rocks, glasses and melts using laser flash analysis which eliminates systematic errors (contact losses and boundary-to-boundary radiative transfer gains) that limit utility of conventional, contact techniques. The database is large enough to elucidate patterns. For most samples and particularly for our >60 non-metallic, large single-crystals, >30 glasses and >12 polycrystals, we show that thermal diffusivity is consistently represented by D(T) =F/T ^G + HT, permitting confident extrapolation from conditions in the laboratory to those in the mantle. The two distinct temperature terms describing D(T) suggest that two microscopic mechanisms of conduction exist in the electrical insulators explored. We propose that phonon scattering (the F/T^G term) sums with radiative diffusion of infrared (IR) light in the form of polaritons (the HT term). Speeds near that of sound over unit cell scale lengths exist for the polariton mechanism due to phonon-photon coupling, thereby distinguishing this proposed mechanism from high frequency diffusive radiative transfer which travels near the speed of light, and only is important following transient heating. For 63 single-crystals and many glasses unaffected by disordering or reconstructive phase transitions, G ranges from 0.3 to 2, depending on structure, and H is ~0.0001/ K, and so HT crosses F/T^G by ~1300 K (for most oxides), meaning that radiative diffusion of IR light is more important than phonon scattering inside the Earth. Importantly, the increase in heat transport due to elevated temperature is augmented by the increase due to high P inside planets, providing stability against convection. The popular view of a vigorously convecting interior needs revisiting, given known feedback in the temperature equation and the large size of the HT term. To understand the microscopic basis of HT term, we re

  12. The origin of a large apparent tortuosity factor for the Knudsen diffusion inside monoliths of a samaria-alumina aerogel catalyst: a diffusion NMR study.

    PubMed

    Mueller, R; Zhang, S; Klink, M; Bäumer, M; Vasenkov, S

    2015-11-01

    Pulsed field gradient (PFG) NMR was applied to measure tortuosity factors for carbon dioxide diffusion in the Knudsen and gas regimes inside monoliths of a samaria-alumina aerogel catalyst, a high porosity material containing micropores in addition to meso- and macropores. The apparent tortuosity factor obtained from PFG NMR measurements for the Knudsen diffusion in the meso- and macropores of the catalyst has an unexpectedly large value of approximately 6 if carbon dioxide adsorption in the micropores and other types of surface adsorption sites of the catalyst is ignored. At the same time, the corresponding apparent tortuosity factor in the gas regime was found to be around 2. Application of a proposed model which describes fast molecular exchange between the surface adsorption sites and the main pore volume of the catalyst yields corrected tortuosity factors which depend only on the pore system geometry. Using this model, the corrected tortuosity factors were found to be around 2 for both diffusion regimes, in agreement with the expectations based on a high porosity of the studied catalyst. PMID:26426141

  13. The Spectrum of the Isotropic Diffuse Gamma-Ray Emission Derived From First-Year Fermi Large Area Telescope Data

    SciTech Connect

    Abdo, A. A.

    2011-08-19

    We report on the first Fermi Large Area Telescope (LAT) measurements of the so-called 'extra-galactic' 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 modelling of the bright foreground diffuse Galactic {gamma}-ray emission (DGE), the detected LAT sources and the solar {gamma}-ray emission. We find the spectrum of the EGB is consistent with a power law with differential spectral index {gamma} = 2.41 {+-} 0.05 and intensity, I(> 100 MeV) = (1.03 {+-} 0.17) x 10{sup -5} cm{sup -2} s{sup -1} sr{sup -1}, where the error is systematics dominated. Our EGB spectrum is featureless, less intense, and softer than that derived from EGRET data.

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

    PubMed

    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. PMID:20366411

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

    SciTech Connect

    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

    2015-05-01

    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.

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

    PubMed Central

    2012-01-01

    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. PMID:23006618

  17. Large-scale optimization-based non-negative computational framework for diffusion equations: Parallel implementation and performance studies

    DOE PAGESBeta

    Chang, Justin; Karra, Satish; Nakshatrala, Kalyana B.

    2016-07-26

    It is well-known that the standard Galerkin formulation, which is often the formulation of choice under the finite element method for solving self-adjoint diffusion equations, does not meet maximum principles and the non-negative constraint for anisotropic diffusion equations. Recently, optimization-based methodologies that satisfy maximum principles and the non-negative constraint for steady-state and transient diffusion-type equations have been proposed. To date, these methodologies have been tested only on small-scale academic problems. The purpose of this paper is to systematically study the performance of the non-negative methodology in the context of high performance computing (HPC). PETSc and TAO libraries are, respectively, usedmore » for the parallel environment and optimization solvers. For large-scale problems, it is important for computational scientists to understand the computational performance of current algorithms available in these scientific libraries. The numerical experiments are conducted on the state-of-the-art HPC systems, and a single-core performance model is used to better characterize the efficiency of the solvers. Furthermore, our studies indicate that the proposed non-negative computational framework for diffusion-type equations exhibits excellent strong scaling for real-world large-scale problems.« less

  18. [Results of immuno-chemotherapeutic treatment of patients with diffuse large B-cell lymphoma].

    PubMed

    Schneider, Tamás; Molnár, Zsuzsanna; Deák, Beáta; Várady, Erika; Tóth, Erika; Csomor, Judit; Matolcsy, András; Lovey, József; Lengyel, Zsolt; Petri, Klára; Gaudi, István; Rosta, András

    2009-11-01

    Treatment with cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) has been considered as the standard therapy for diffuse large B-cell lymphoma (DLBCL) for more than 20 years. CHOP treatment in combination with targeted immunotherapy, rituximab (R-CHOP), resulted in significant improvements in the treatment of this group of patients. In this study, efficacy of R-CHOP and R-CHOP-like treatments was analysed. Results were compared to the data of historical patients only receiving CHOP treatment or CHOP-like treatment. Between September 2002 and April 2005, 140 newly diagnosed, untreated DLBCL patients started to receive R-CHOP treatment in a single centre. The eligibility criteria included advanced stage (clinical stages III-IV), or large tumour size (>7 cm) and/or symptom B or extranodal manifestation in the case of clinical stages I-II. The results were compared to the data of 130 patients only receiving CHOP treatment in the past. In the patients receiving R-CHOP, the therapeutic outcomes were superior for all parameters. During an average follow-up period of 44 or 52 months, the overall remission rate was 73.6% in the R-CHOP group in comparison with 47.7% in the CHOP group. The 5-year overall survival was 68.6% vs. 41.0% (RR: 0.4293, CI: 0.2963-0.6221; p < 0.0001), the event-free survival was 59.8% vs. 33.5% (RR: 0.5038, CI: 0.3606-0.7038; p < 0.0001) and the progression-free survival was 64.4% vs. 37.6% (RR: 0.4915, CI: 0.3442-0.7019; p < 0.0001). Since prognostic parameters were more favourable in the R-CHOP group, patient groups were also compared using the International Prognostic Index score. Again, significant differences were revealed by the subgroup analyses. The 5-year overall survival was 74.4% vs. 47.9% (RR: 0.4475, CI: 0.2418-0.8285; p = 0.0084) and 52.0% vs. 28.8% (RR: 0.4989, CI: 0.3098-0.8035; p = 0.003) in the group with good prognosis and in the group with poor prognosis, respectively. In the group with very good prognosis, the

  19. Responding to AIDS-related bereavement in the South African context.

    PubMed

    Demmer, Craig

    2007-10-01

    AIDS continues to be a death sentence for many individuals living in South Africa where it remains the leading cause of death. Little is currently known about what it is like to experience the loss of a loved one to AIDS from the South African perspective and how to assist individuals who are living in a context vastly different from similarly bereaved individuals in the West. The purpose of this article is to discuss contextual issues that may affect individuals in South Africa who are grieving AIDS-related deaths and to offer preliminary suggestions on how to help these individuals. The author draws on his experience in the province of KwaZulu-Natal working with people affected by the HIV/AIDS epidemic, as well as discussions with practitioners involved in HIV/AIDS care in this region. PMID:17886413

  20. Gender and AIDS-related psychosocial processes: a study of perceived susceptibility, social distance, and homophobia.

    PubMed

    Schieman, S

    1998-06-01

    Over the past decade, researchers have accumulated evidence that suggests six main factors are associated with AIDS-related risk reduction behavior: (a) perceived susceptibility (Dolcini et al., 1995; van der Plight & Richard, 1994); (b) attitudes toward condoms (Catania et al., 1994; Maticka-Tynadale, 1991); (c) personally knowing someone with HIV/AIDS (Joseph et al., 1987); (d) perceived peer norms about risk-reduction (Maticka-Tyndale, 1991); (e) previous sexual activity (Joseph et al., 1987); and (f) self-efficacy (Aspinwall, Kemeny, Taylor, & Schneider, 1991; van der Plight & Richard, 1994). Furthermore, there is some suggestion that the epidemiology and sociocultural constructions of the disease has led to considerable gender, racial, and class differences in awareness of AIDS, perception of HIV threat, and HIV-relevant behavior (Cohan & Atwood, 1994; Dolcini et al., 1995; Gillies, 1994). PMID:9642424

  1. Understanding and Addressing AIDS-Related Stigma: From Anthropological Theory to Clinical Practice in Haiti

    PubMed Central

    Castro, Arachu; Farmer, Paul

    2005-01-01

    For the past several years, diverse and often confused concepts of stigma have been invoked in discussions on AIDS. Many have argued compellingly that AIDS-related stigma acts as a barrier to voluntary counseling and testing. Less compelling are observations regarding the source of stigma or its role in decreasing interest in HIV care. We reviewed these claims as well as literature from anthropology, sociology, and public health. Preliminary data from research in rural Haiti suggest that the introduction of quality HIV care can lead to a rapid reduction in stigma, with resulting increased uptake of testing. Rather than stigma, logistic and economic barriers determine who will access such services. Implications for scale-up of integrated AIDS prevention and care are explored. PMID:15623859

  2. Diffuse gamma-ray emission from pulsars in the Large Magellanic Cloud

    NASA Technical Reports Server (NTRS)

    Hartmann, Dieter H.; Brown, Lawrence E.; Schnepf, Neil

    1993-01-01

    We investigate the contribution of pulsars to the diffuse gamma-ray emission from the LMC. The pulsar birth rate in the LMC is a factor of about 10 lower than that of the Galaxy and the distance to pulsars in the LMC is about 5-10 times larger than to Galactic pulsars. The resulting total integrated photon flux from LMC pulsars is thus reduced by a factor of about 100 to 1000. However, the surface brightness is not reduced by the same amount because of the much smaller angular extent of the LMC in comparison to the diffuse glow from the Galactic plane. We show that gamma-ray emission due to pulsars born in the LMC could produce gamma-ray fluxes that are larger than the inverse Compton component from relativistic cosmic-ray electrons and a significant fraction of the extragalactic isotropic background or the diffuse Galactic background in that direction. The diffuse pulsar glow above 100 MeV should therefore be included in models of high-energy emission from the LMC. For a gamma-ray beaming fraction of order unity the detected emissions from the LMC constrain the pulsar birth rate to less than one per 50 yr. This limit is about one order of magnitude above the supernova rate inferred from the historic record or from the star-formation rate.

  3. Uncovering Implicit Assumptions: A Large-Scale Study on Students' Mental Models of Diffusion

    ERIC Educational Resources Information Center

    Stains, Marilyne; Sevian, Hannah

    2015-01-01

    Students' mental models of diffusion in a gas phase solution were studied through the use of the Structure and Motion of Matter (SAMM) survey. This survey permits identification of categories of ways students think about the structure of the gaseous solute and solvent, the origin of motion of gas particles, and trajectories of solute particles in…

  4. AIDS-related knowledge, attitudes and behaviour among South African street youth: reflections on power, sexuality and the autonomous self.

    PubMed

    Swart-Kruger, J; Richter, L M

    1997-09-01

    Street children in South Africa are, in the main, between the ages of 11 and 17 years. Rape, prostitution, sexual bartering and exchange, casual sex and romantic sexual relationships all occur in the experiences of young people who live and work on inner-city streets. In this study, the AIDS-related knowledge, attitudes and behaviour of 141 street youth, living in seven large cities in South Africa, were elicited in focus group discussions. At the time of the study, 79 boys (56%) were living in shelters run by nongovernmental and welfare organisations, while 62 boys (44%) were sleeping "rough". The results, both qualitative and quantitative, indicated that the AIDS knowledge of South African street children was comparable to levels reported for groups of "hard-to-reach" youth in other parts of the world. Fear of HIV infection did not appear in a list of day-to-day priorities constructed by the children, a list dominated by survival concerns with food, money and clothes. However, more than half of the boys conceded that they engaged in sex for money, goods or protection, several boys indicated that they had been raped, and most reported being sexually active with "girlfriends", who themselves frequently engaged in transactional sex. The findings are interpreted in terms of the relationships between power dynamics surrounding race and age, and how they affect self-initiated controls over sexuality and sexual protection. PMID:9255928

  5. A systematic review of HIV/AIDS-related stigma and discrimination in India: current understanding and future needs.

    PubMed

    Bharat, Shalini

    2011-01-01

    HIV/AIDS-related stigma is recognised as a major barrier to HIV prevention efforts and an impediment to mitigating its impact on individuals and communities. This paper reviews the existing research literature on AIDS stigma in India with the objective of documenting the current status of research, highlighting major findings and identifying key gaps remaining. Thirty publications were identified through a careful search of which a majority focused on stigma assessment and very few on stigma measurement, conceptual aspects of stigma or stigma reduction interventions. A few standardised stigma measures are available but more are required to assess causes of stigma among general population and compounded and internalised stigma among positive people. Research exploring linkages between stigma and HIV services uptake or the effect of HIV care and treatment programs on stigma levels are largely missing and need to be prioritised. In addition, more research is needed to advance conceptual understanding of stigma within the cultural context of the country including research on the neglected groups such as, transgender people. Context-specific (health care, community) interventions are needed to address various forms of stigma - enacted, perceived, internalised and layered - including structural approaches besides inter-personal and information-based approaches. A major gap relates to meager research on developing and evaluating stigma reduction interventions and needs priority focus. Overall, the review recommends developing a national agenda on AIDS stigma research and interventions to help realise the government's goal of stigma reduction. PMID:23237728

  6. Understanding Internalized HIV/AIDS-Related Stigmas in the Dominican Republic: A Short Report

    PubMed Central

    Hampanda, Karen

    2016-01-01

    HIV/AIDS-related stigmas can become internalized, resulting in declines in physical and mental health. Pathways to internalized HIV-related stigma (IS), characterized by persistently negative, self-abasing thoughts, are not well established among women living with HIV/AIDS (WLWHA) in the Dominican Republic (DR). Identifying factors involved in self-directed shaming and blaming is important, given the high HIV prevalence in the DR’s most vulnerable populations. The present study sheds light on factors involved in negative and self-abasing thoughts in WLWHA in the DR by examining the relationship between depression, perceived HIV-related stigma from the community (PSC), perceived HIV-related stigma from family (PSF) and IS. The Internalized AIDS-Related Stigma Scale (IA-RSS), the Center for Epidemiologic Studies Short Depression Scale (CES-D 10), and an instrument designed to measure perceived HIV-related stigma from the community and family was administered to 233 WLWHA in Puerto Plata, DR. Data were analyzed using descriptive statistics and ordered multiple logistic regression. Results showed that depression (OR=1.60; p<0.05), PSC (OR=3.68; p<0.001), and PSF (OR=1.60; p<0.01) were positively associated with IS. These findings indicate that IS-reducing interventions should address HIV-related depression. Additionally, HIV-related treatment and care services should work with WLWHA to adopt healthier attitudes about how community members view people living with HIV/AIDS in the Dominican Republic. PMID:26466239

  7. Understanding internalized HIV/AIDS-related stigmas in the Dominican Republic: a short report.

    PubMed

    Rael, Christine Tagliaferri; Hampanda, Karen

    2016-03-01

    HIV/AIDS-related stigmas can become internalized, resulting in declines in physical and mental health. Pathways to internalized HIV-related stigma (IS), characterized by persistently negative, self-abasing thoughts, are not well established among women living with HIV/AIDS (WLWHA) in the Dominican Republic (DR). Identifying factors involved in self-directed shaming and blaming is important, given the high HIV prevalence in the DR's most vulnerable populations. The present study sheds light on factors involved in negative and self-abasing thoughts in WLWHA in the DR by examining the relationship between depression, perceived HIV-related stigma from the community (PSC), perceived HIV-related stigma from family (PSF), and IS. The Internalized AIDS-Related Stigma Scale (IA-RSS), the Center for Epidemiologic Studies Short Depression Scale (CES-D 10), and an instrument designed to measure perceived HIV-related stigma from the community and family was administered to 233 WLWHA in Puerto Plata, DR. Data were analyzed using descriptive statistics and ordered multiple logistic regression. Results showed that depression (OR = 1.60; p < .05), PSC (OR = 3.68; p < .001), and PSF (OR = 1.60; p < .01) were positively associated with IS. These findings indicate that IS-reducing interventions should address HIV-related depression. Additionally, HIV-related treatment and care services should work with WLWHA to adopt healthier attitudes about how community members view people living with HIV/AIDS in the DR. PMID:26466239

  8. Circulating Mediators of Inflammation and Immune Activation in AIDS-Related Non-Hodgkin Lymphoma

    PubMed Central

    Nolen, Brian M.; Breen, Elizabeth Crabb; Bream, Jay H.; Jenkins, Frank J.; Kingsley, Lawrence A.; Rinaldo, Charles R.; Lokshin, Anna E.

    2014-01-01

    Background Non-Hodgkin lymphoma (NHL) is the most common AIDS-related malignancy in developed countries. An elevated risk of developing NHL persists among HIV-infected individuals in comparison to the general population despite the advent of effective antiretroviral therapy. The mechanisms underlying the development of AIDS-related NHL (A-NHL) are not fully understood, but likely involve persistent B-cell activation and inflammation. Methods This was a nested case-control study within the ongoing prospective Multicenter AIDS Cohort Study (MACS). Cases included 47 HIV-positive male subjects diagnosed with high-grade B-cell NHL. Controls were matched to each case from among participating HIV-positive males who did not develop any malignancy. Matching criteria included time HIV+ or since AIDS diagnosis, age, race and CD4+ cell count. Sera were tested for 161 serum biomarkers using multiplexed bead-based immunoassays. Results A subset of 17 biomarkers, including cytokines, chemokines, acute phase proteins, tissue remodeling agents and bone metabolic mediators was identified to be significantly altered in A-NHL cases in comparison to controls. Many of the biomarkers included in this subset were positively correlated with HIV viral load. A pathway analysis of our results revealed an extensive network of interactions between current and previously identified biomarkers. Conclusions These findings support the current hypothesis that A-NHL develops in the context of persistent immune stimulation and inflammation. Further analysis of the biomarkers identified in this report should enhance our ability to diagnose, monitor and treat this disease. PMID:24922518

  9. The political context of AIDS-related stigma and knowledge in a South African township community.

    PubMed

    Forsyth, Brian; Vandormael, Alain; Kershaw, Trace; Grobbelaar, Janis

    2008-07-01

    The purpose of this study was to examine the presentation of AIDS-related stigma and knowledge within the political context of the South African government's response to the AIDS epidemic. It was during the 2000 - 2004 period that key government officials publicly challenged the orthodox views of HIV/AIDS, with the South African president, Thabo Mbeki, actively positing the primary role of poverty and other socio-economic stressors in the progression of the AIDS epidemic. This discursive position had real-time effects for AIDS policy-making and ultimately delayed the implementation of a national antiretroviral (ARV) rollout programme. Consequently this position was criticised by commentators in the media and elsewhere for contributing to an already widespread climate of AIDS stigmatization and misinformation. To shed more light on these claims we conducted a survey in 2005 in Atteridgeville, a South African township, and compared results with those of a similar survey conducted shortly after ARV medications became available in 2004. Results indicated a reduction in AIDS stigma levels across the 1-year period, and that those participants who endorsed contentious political views (such as those expressed by key government officials) were more likely to have a higher level of AIDS-related stigma than those who disagreed. Nevertheless, this study cautions against drawing a causal relationship between the South African government's position and IDS-stigmatizing attitudes, and suggests that further political and social factors be accounted for in an attempt to gain a fuller understanding of this seemingly complex relationship. PMID:18709210

  10. Parameterization of large-scale turbulent diffusion in the presence of both well-mixed and weakly mixed patchy layers

    NASA Astrophysics Data System (ADS)

    Osman, M. K.; Hocking, W. K.; Tarasick, D. W.

    2016-06-01

    general degrees of mixing. We show that it is the largest, most vigorous and less common turbulent layers that make the major contribution to global diffusion. Finally, we make estimates of global-scale diffusion coefficients in the lower stratosphere and upper troposphere. For the lower stratosphere, κeff ≈ 2x10-2 m2 s-1, assuming no other processes contribute to large-scale diffusion.

  11. Evolution of frontline treatment of diffuse large B-cell lymphoma: a brief review and recent update.

    PubMed

    Hong, Jung Yong; Suh, Cheolwon; Kim, Won Seog

    2016-01-01

    Various strategies have been implemented to improve the outcomes of diffuse large B-cell lymphoma (DLBCL). In recent years, remarkable advances have been achieved, based on the discovery of cell-of-origin in DLBCL and on more effective targeted agents. This commentary will summarize recent updates on the evolution of frontline therapies for DLBCL, focusing on the upcoming promising frontline chemotherapy platforms and on activated B-cell subtype DLBCL and double-hit DLBCL. PMID:27606052

  12. Evolution of frontline treatment of diffuse large B-cell lymphoma: a brief review and recent update

    PubMed Central

    Hong, Jung Yong; Suh, Cheolwon; Kim, Won Seog

    2016-01-01

    Various strategies have been implemented to improve the outcomes of diffuse large B-cell lymphoma (DLBCL). In recent years, remarkable advances have been achieved, based on the discovery of cell-of-origin in DLBCL and on more effective targeted agents. This commentary will summarize recent updates on the evolution of frontline therapies for DLBCL, focusing on the upcoming promising frontline chemotherapy platforms and on activated B-cell subtype DLBCL and double-hit DLBCL.

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

    Cancer.gov

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

  14. Dual expression of MYC and BCL2 proteins predicts worse outcomes in diffuse large B-cell lymphoma.

    PubMed

    Clark Schneider, Kelli M; Banks, Peter M; Collie, Angela M B; Lanigan, Christopher P; Manilich, Elena; Durkin, Lisa M; Hill, Brian T; Hsi, Eric D

    2016-07-01

    Recent studies suggested that MYC and BCL2 protein co-expression is an independent indicator of poor prognosis in diffuse large B-cell lymphoma. However, the immunohistochemistry protocols for dual-expression staining and the scoring cut-offs vary by study. Sixty-nine cases of diffuse large B-cell lymphoma were evaluated for MYC and BCL2 protein expression using various cut-offs that have been recommended in prior studies. Independent of the International Prognostic Index risk group, cases with dual protein expression of BCL2 and MYC using ≥50%/40% cut-offs and ≥70%/40% had significantly shorter overall survival than cases without. It was verified in this patient population that the use of BCL2 and MYC immunohistochemistry, performed with available in vitro diagnostic-cleared antibodies, provides rapid prognostic information in patients with de novo diffuse large B-cell lymphoma. This study has practical implications for diagnostic laboratories and serves as a guide for implementation in the setting of future clinical trials. PMID:26421520

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

    DOE PAGESBeta

    Han, Yong; Evans, James W.

    2015-10-27

    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 C6-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 inmore » 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. Furthermore, this in turn enables simulation studies elucidating diffusion-mediated directed-assembly of Ru nanoclusters during deposition of Ru on G/Ru(0001).« less

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

    SciTech Connect

    Han, Yong; Evans, James W.

    2015-10-27

    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 C6-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. Furthermore, this in turn enables simulation studies elucidating diffusion-mediated directed-assembly of Ru nanoclusters during deposition of Ru on G/Ru(0001).

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

    SciTech Connect

    Han, Yong; Evans, James W.

    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)

  18. Design and implementation of ultra-high resolution, large bandwidth, and compact diffuse light spectrometers

    NASA Astrophysics Data System (ADS)

    Badieirostami, Majid

    To realize spectrometers with state-of-the-art performance measures, we need to combine novel synthetic material properties and new device concepts using efficient design and optimization tools. Considering the material engineering, device innovation, and modeling and simulation tool development as the three primary areas of research in the invention of modern spectrometers, I put myself at the intersection of these three areas. My Ph.D. research has been focused on the development of such infrastructures for next generation spectrometers. My research on the new concepts for spectrometer has been focused on the development of true multi-dimensional spectrometers, which use a multi-dimensional [two-dimensional (2D) or 3D] mapping of the spectral information into space. While the conventional spectrometers use a grating to form a one-dimensional (1D) spatial-spectral mapping, I showed that by combining a simple dispersive element (a volume hologram) formed in very inexpensive polymers with a basic Fabry-Perot interferometer, we can form a spectrometer with ultra-high resolution over a large spectral bandwidth, which surpasses all conventional spectrometers. This unique performance is obtained by the 2D spatial-spectral mapping enabled by combining two simple optical functionalities. I strongly believe that the extension of this mapping into three dimensions by using synthetic nanophotonic structures with engineered dispersion (optimized using the recently demonstrated modeling tool) can further improve the performance and reduce the overall spectrometer size into the micron regime. The need for efficient modeling and simulation tools comes from the sophisticated nature of the new 3D nanophotonic structures, which makes their simple analysis using well-known simple formulas for the propagation of the electromagnetic fields in bulk materials impossible. On the other hand, direct numerical simulation of these structures using the well-known numerical simulation tools

  19. A method to analyze the diffuse gamma-ray emission with the Fermi Large Area Telescope

    SciTech Connect

    Ackermann, Markus; Johannesson, Gueolaugur; Digel, Seth; Moskalenko, Igor V.; Reimer, Olaf; Porter, Troy; Strong, Andrew

    2008-12-24

    The Fermi Gamma-Ray Space Telescope with its main instrument the LAT is the most sensitive {gamma}-ray telescope in the energy region between 30 MeV and 100 GeV. One of the prime scientific goals of this mission is the measurement and interpretation of the diffuse Galactic and extragalactic {gamma}-ray emission. While not limited by photon statistics, this analysis presents several challenges: Instrumental response functions, residual background from cosmic rays as well as resolved and unresolved foreground {gamma}-ray sources have to be taken carefully into account in the interpretation of the data. Detailed modeling of the diffuse {gamma}-ray emission is being performed and will form the basis of the investigations. We present the analysis approach to be applied to the Fermi LAT data, namely the modeling of the diffuse emission components and the background contributions, followed by an all-sky maximum-likelihood fitting procedure. We also report on the performance of this method evaluated in tests on simulated Fermi LAT and real EGRET data.

  20. Classical Hodgkin lymphoma primary refractory to brentuximab vedotin, with transformation to CD30-positive diffuse large B-cell lymphoma.

    PubMed

    Makita, Shinichi; Maeshima, Akiko Miyagi; Taniguchi, Hirokazu; Kitahara, Hideaki; Fukuhara, Suguru; Munakata, Wataru; Suzuki, Tatsuya; Maruyama, Dai; Kobayashi, Yukio; Tobinai, Kensei

    2016-09-01

    Brentuximab vedotin (BV) is an antibody-drug conjugate that targets CD30. It is highly effective for relapsed/refractory classical Hodgkin lymphoma (CHL), and has become a promising treatment option for these patients; however, approximately 25 % of patients are refractory to BV. Until now, the clinicopathologic features of CHL refractory to BV have not been well understood. Here, we report a patient with relapsed CHL with an unfavorable outcome, whose disease was primary refractory to BV and was histologically diagnosed as a transformation from mixed cellularity CHL to CD30-positive diffuse large B-cell lymphoma (DLBCL). The transformation to DLBCL showing high tumor density and high proliferative activity (Ki67 index >90 %) was possibly related to the primary refractory to BV and an aggressive clinical course, although the lymphoma was diffusely and strongly positive for CD30. PMID:27169615

  1. AIDS as social construction: text mining of AIDS-related information in the Italian press.

    PubMed

    Caputo, Andrea; Giacchetta, Agnese; Langher, Viviana

    2016-09-01

    Given the relevance of AIDS as a public health problem in the Italian context and of the role of mass media in the social construction of the phenomenon, the aim of the present study is twofold: (1) to explore the main AIDS-related themes in the Italian popular press; (2) to analyse the temporal trends of AIDS representations over the last decades. For the research, we decided to consult Italian newspaper articles produced between 1985 and 1990 and between 2005 and 2010 using the archives of the main two national newspapers (La Repubblica and Corriere della Sera), resulting in an overall sample of 446 newspaper articles. A computer-aided content analysis allowed the detection of five different thematic domains (clusters), respectively focused on: Medical care (7.47%), Family support (37.03%), Science and religion debate (27%), Social exclusion (17.6%) and Healthcare policies (10.9%). These thematic domains are conceived along two main latent dimensions (factors) which explain 72.47% of the data variance which respectively deal with: (1) Attitudes towards people with AIDS (care versus avoidance) and (2) Social mandate on AIDS (powerlessness versus control). The study results also reveal the potential evolution of representations of people with AIDS over time: from stigmatised subjects who represent a risk for the entire society within a climate of social control to people progressively symbolised as frail subjects that need to be taken care of. PMID:26923156

  2. Effect of unintentional cyclophosphamide underdosing on diffuse large B-cell lymphoma response to chemotherapy: a retrospective review

    PubMed Central

    Al-Ahmadi, Majed; Lazo-Langner, Alejandro; Mangel, Joy; Phm, Ally Dhalla BSc; Liu, Kevin; Minuk, Leonard

    2016-01-01

    Background: Between March 2012 and March 2013, a miscommunication in labelling between the drug compounder supplier and cancer centre pharmacies resulted in accidental overdilution of cyclophosphamide and gemcitabine used by several cancer centres in Canada. At our centre, 177 hematology patients were affected, among whom the largest subset of patients was those with diffuse large B-cell lymphoma. In this study, we evaluated the effect of such underdosing on disease response. Methods: We conducted a retrospective cohort study involving all patients with diffuse large B-cell lymphoma who received at least 1 chemotherapy cycle containing diluted cyclophosphamide at our centre and compared them with a historical group of patients matched by stage and age. The primary outcome was event-free survival (a composite of disease progression or death). Secondary outcomes included complete remission and overall response rate. Groups were compared using unpaired Student t, χ2 or Fisher exact tests, as appropriate. Survival analysis was done using the Kaplan-Meier method. Results: Event-free survival was no different between groups (log-rank p = 0.99). At a median follow-up of 548 days, progression or death occurred in 21 of 77 patients in the case group (27.3%) and in 24 of 74 patients in the control group (32.4%) (p = 0.5). At the end of treatment, complete remission was achieved in 41 patients in the case group (53.2%) and 43 patients in the control group (57.3%) (p = 0.6), whereas overall response rate was 71.4% in the case group and 66.7% in the control group (p = 0.5). Interpretation: Compared with a historical control group, we found no differences in event-free survival or response rates among patients with diffuse large B-cell lymphoma who received 1 or more doses of accidentally diluted cyclophosphamide-containing chemotherapy.

  3. (18)FDG PET/CT appearance in primary cutaneous diffuse large B-cell lymphoma, leg type.

    PubMed

    Samarghandi, Amin; Gru, Alejandro Ariel; Natwa, Mona; Barker, David W

    2015-06-01

    We report the case of a 70-year-old woman who presented with a small and painless red skin nodule in the right lower leg, which rapidly and significantly increased in size over few weeks and developed a central eschar. Skin biopsy was consistent with primary cutaneous diffuse large B-cell lymphoma, leg type (PCDBCL-LT), an aggressive and rare cutaneous lymphoma. F-FDG PET/CT showed a hypermetabolic soft tissue mass in the right leg with no evidence of systemic involvement of disease. PMID:25742229

  4. Diffuse large B-cell lymphoma in the sphenoid sinus mimicking fibrous dysplasia in CT and MRI

    PubMed Central

    Yoshihara, Shintaro; Kondo, Kenji; Ochi, Atsushi

    2014-01-01

    We present a 70-year-old man with lymphoma who presented with a right eye movement disorder. CT examinations showed ‘ground-glass’ appearance extending around the right sphenoid sinus which suggested fibrous dysplasia. However, biopsy from the mass histologically proved it to be diffusing large B-cell lymphoma and positron emission tomography examinations revealed increased fluorodeoxyglucose (FDG) uptake around the right sphenoid bone and multiple spinal bones. After chemotherapy for lymphoma, abnormal FDG uptake disappeared from the body. PMID:25100815

  5. Anti-tumor activity of the combination of bendamustine with vorinostat in diffuse large B-cell lymphoma cells.

    PubMed

    Fernández-Rodríguez, Concepción; Salar, Antonio; Navarro, Alfons; Gimeno, Eva; Pairet, Silvia; Camacho, Laura; Ferraro, Mariana; Serrano, Sergi; Besses, Carles; Bellosillo, Beatriz; Sanchez-Gonzalez, Blanca

    2016-03-01

    Current standard-of-care therapy for diffuse large B-cell lymphoma (DLBCL) results in up to 40% of patients who either relapse or develop refractory disease. In this setting, further therapeutic improvements are needed. This study analyzed the in vitro effects of the combination of bendamustine with the histone deacetylase inhibitor vorinostat in DLBCL cells. This combination enhanced histone acetylation and double strand DNA breaks resulting in an additive to synergistic cytotoxic effect in both ABC- and GCB-type DLBCL cells, independently of their TP53 mutational status. These results support the rationale for considering bendamustine and vorinostat combination as a novel approach in DLBCL treatment. PMID:26084206

  6. Combined heat transfer in floating zone growth of large silicon crystals with radiation on diffuse and specular surfaces

    NASA Astrophysics Data System (ADS)

    Guo, Zhixiong; Maruyama, Shigenao; Togawa, Shinji

    1998-01-01

    Numerical analyses are conducted to investigate the combined heat transfer in floating zone growth of large Si crystals with needle-eye technique. The radiation element method, REM2, is employed to determine the radiative heat exchange, in which the view factors associated with the components in the float zone furnace and both the diffuse and specular reflection components are incorporated. The boundary element method and the finite difference method are adopted to calculate the electromagnetic field and the heat conduction, respectively. The effect of surface radiative characteristics of Si melt and crystal, i.e., diffuse and/or specular, is discussed in detail. It is found that the consideration of specular surfaces increases the Joulean heat and the radiative heat flux. The temperature fields are obtained for the cases of diffuse and specular, and the difference between the two different cases is obvious in the crystal and molten zone areas. The molten zone is enlarged when the specular surface is accounted for. The interface shape is examined and found to be in good agreement with the experiment.

  7. Tracking timescales of short-term precursors to large basaltic fissure eruptions through Fe-Mg diffusion in olivine

    NASA Astrophysics Data System (ADS)

    Hartley, Margaret E.; Morgan, Daniel J.; Maclennan, John; Edmonds, Marie; Thordarson, Thor

    2016-04-01

    Petrological constraints on the timescales of pre-eruptive crystal storage and magma degassing provide an important framework for the interpretation of seismic, geodetic and gas monitoring data in volcanically active regions. We have used Fe-Mg diffusion chronometry in 86 olivine macrocrysts from the AD 1783-1784 Laki eruption on Iceland's Eastern Volcanic Zone to characterise timescales of crystal storage and transport in the lead-up to this eruption. The majority of these olivines have core compositions of Fo < 76, and rim compositions in the range Fo69-Fo74 that are close to equilibrium with the Laki melt. Diffusion modelling using the greyscale intensity of backscattered electron images as a proxy for olivine composition reveals that the most probable Fe-Mg diffusion timescale for Laki olivines is 7.8 days, which reflects the characteristic olivine residence time in the carrier melt prior to eruption. A small population of Fo > 81 olivines record Fe-Mg diffusion timescales of ∼124 days; these crystals are likely to have formed in mid-crustal magma chambers, been transferred to storage at shallower levels and then entrained into the Laki melt prior to eruption. Typical Fe-Mg diffusion timescales of 6-10 days are shorter than the average time interval between discrete episodes of the Laki eruption, indicating variable or pulsed disaggregation of stored crystals into the carrier liquid prior to the onset of each episode. The diffusion timescales coincide with historical accounts of strong and frequent earthquakes in southeast Iceland, which we interpret as being associated with mush disaggregation related to melt withdrawal and the initiation of dyke propagation from a crustal magma reservoir at ∼6 ± 3 km depth to the surface. We calculate pre-eruptive CO2 fluxes of 2-6 Mt d-1, assuming a pre-eruptive CO2 outgassing budget of 189.6 Mt for the Laki eruption and a constant rate of CO2 release in the 6-10 days preceding each eruptive episode. Our dataset

  8. Reducing AIDS-related stigma in developing countries: the importance of theory- and evidence-based interventions.

    PubMed

    Bos, Arjan E R; Schaalma, Herman P; Pryor, John B

    2008-08-01

    In many developing countries persons living with HIV and AIDS experience strong stigma and discrimination, and AIDS-related stigma has an enormous negative impact on their social relationships, access to resources, and psychological well being. Moreover, AIDS-related stigma hampers HIV-related health promotion, including voluntary HIV counselling and testing. In this article, we will argue that programs to reduce AIDS-related stigma are most likely to be effective if these programs are based upon thorough needs assessments, theory- and evidence-based intervention strategies and collaborative planning. A protocol for health promotion programs design is outlined. Furthermore, psychosocial correlates of AIDS-related stigma in developing countries, social-psychological theories that might be useful in designing intervention strategies to reduce stigmatisation and successful elements of previous interventions aimed at stigma reduction are discussed. It is concluded that psychological theory does provide guidelines for the development of stigma-reducing intervention programs, but that such programs can only be effective when based upon context-specific needs assessment and collaborative planning. PMID:18825583

  9. Fragmented Molecular Orbital with Diffusion Monte Carlo for large molecular systems

    NASA Astrophysics Data System (ADS)

    Benali, Anouar; Pruitt, Spencer R.; Fedorov, Dmitri G.

    Performing accurate quantum mechanics (QM) calculations on larger and larger systems, while maintaining a high level of accuracy is an ongoing effort in many ab initio fields. Many different attempts have been made to develop highly scalable and accurate methods. The fragment molecular orbital (FMO) method is an ab initio method capable of taking advantage of modern supercomputers, such as the Blue Gene Q system Mira at the Argonne National Laboratory Leadership Computing Facility (ALCF). FMO is based on dividing molecules into fragments and performing ab initio calculations on fragments, their dimers and, optionally, trimers. This decomposition makes it possible to perform QM calculations of real size biological molecules. In contrast to many other fragment-based methods, the effect of the environment is rigorously accounted for by computing the electrostatic potential (ESP) due to remaining fragments that are not explicitly included in a given monomer, dimer, or trimer calculation. The use of highly accurate levels of theory, such as Diffusion Monte Carlo (DMC-QMC), in conjunction with FMO allows for the goal of highly scalable and accurate all electron calculations demonstrated in this study, on a variety of relevant systems (H2O)[3-6] and protein using GAMESS and QMCPACK.

  10. HIV/AIDS-Related Knowledge and Behaviors Among Most-at-Risk Populations in Vietnam

    PubMed Central

    Vian, Taryn; Semrau, Katherine; Hamer, Davidson H; Loan, Le Thi Thanh; Sabin, Lora L

    2012-01-01

    The U.S. President’s Emergency Plan for AIDS Relief (PEPFAR) has supported the Vietnamese Ministry of Health (MOH) in implementing behavior change strategies to slow the HIV epidemic. These programs target commercial sex workers (CSW), injection drug users (IDU), and men who have sex with men (MSM). Using data from a program evaluation to assess effectiveness of the PEPFAR intervention, we conducted a sub-analysis of HIV/AIDS knowledge, sexual behaviors, and injection drug risk behaviors among 2,199 Vietnamese respondents, including those reporting recent contact with an outreach worker and those who did not report contact. We found overall high levels of HIV/AIDS knowledge, low rates of needle sharing, and moderate to high rates of inconsistent condom use. Average knowledge scores of IDU were significantly higher than non-IDU for antiretroviral treatment knowledge, while MSM had significantly less knowledge of treatment compared to non-MSM. HIV/AIDS-related knowledge was not significantly associated with needle-sharing practices. Knowledge was modestly but significantly associated with more consistent use of condoms with primary and commercial sex partners, even after controlling for contact with an outreach worker. Contact with an outreach worker was also an independent predictor of more consistent condom use. Outreach programs appear to play a meaningful role in changing sexual behavior, though the effect of outreach on IDU risk behaviors was less clear. More research is needed to understand the relationship between outreach programs and skill development, motivation, and use of referral services by most-at-risk populations in Vietnam. PMID:23173025

  11. HIV/AIDS Related Stigma and Discrimination against PLWHA in Nigerian Population

    PubMed Central

    Bulgiba, Awang; Oche, Oche Mansur; Adekunjo, Felix Oluyemi

    2015-01-01

    Background HIV/AIDS remain a major public health concern in Nigeria. People living with HIV/AIDS (PLWHA) face not only personal medical problems but also social problems associated with the disease such as stigma and discriminatory attitudes. This study provides an insight into HIV/AIDS related stigma and discrimination against PLWHA in Nigeria. Methods The data for this study was extracted from the 2013 Nigeria Demographic and Health Survey conducted by the National Population Commission. All men and women aged 15–49 years, permanent residents and visitors of the households were eligible for the interview. Several questionnaires were used in the survey, some covering questions on HIV/AIDS. Results A total of 56 307 men and women aged 15–49 years participated in this national survey. About half of the population in Nigeria have HIV stigma. Younger persons, men, those without formal education and those within poor wealth index are more likely to have stigma towards PLWHA. In addition, married people are more likely to have stigma on PLWHA and are more likely to blame PLWHA for bringing the disease to the community. Also about half of the population discriminates against PLWHA. However, those with higher levels of education and those from higher wealth index seem to be more compassionate towards PLWHA. About 70% in the population are willing to care for relative with AIDS, even more so among those with higher level of education. Conclusion There is a high level of HIV stigma and discrimination against PLWHA in the Nigerian population. Education seems to play a major role in the society with respect to HIV stigma and discrimination against PLWHA. Educating the population with factual information on HIV/AIDS is needed to reduce stigma and discrimination towards PLWHA in the community. PMID:26658767

  12. MUM-1 and bcl-2 Positive Primary Diffuse Large B Cell Non-Hodgkin's Lymphoma of the Colon.

    PubMed

    Jurisić, Vladimir; Plećić, Mirjana; Colović, Natasa; Čemerikić-Martinović, Vesna; Janković, Marko; Čolović, Milica

    2016-04-01

    Primary diffuse large B cell lymphoma (DLBCL) presents as a nodal and extranodal disease. The most common extranodal site is the gastrointestinal tract (GI), with the stomach most frequently involved, followed by the small bowel. Primary DLBCL of the large bowel accounts for 0.2%-1.2% of all colonic tumors. We present two patients who underwent radical resections of right colonic tumors. They were diagnosed with primary colonic DLBCL following histological and immunohistochemical testing of the excised tissues, and were determined as being in stage IIE of the disease. The tumors expressed CD20 markers. Both received multi-agent chemotherapy with combined immunotherapy and remain in complete remission at 4 and 5 years. PMID:27041528

  13. Primary diffuse large B-cell lymphoma in the anterior hard palate: A rare case report with review of literature

    PubMed Central

    Sahoo, Sujit Ranjan; Misra, Satya Ranjan; Mishra, Lora; Mishra, Sobhan

    2014-01-01

    Diffuse large B-cell lymphomas (DLBCLs) are defined as neoplasms of large transformed B cells, i.e. with nuclear diameter more than twice that of a normal lymphocyte. These account for 30-40% of all adult non-Hodgkin's lymphomas (NHL). Intraoral lymphomas are relatively rare and often difficult to diagnose in clinical settings. In this case report, we describe a case of primary DLBCL affecting the anterior part of the hard palate of an elderly male patient. DLBCL of anterior part of hard palate is yet to be reported in the English literature, even though DLBCL cases involving the posterior palate have been recorded, thus making the present case to be first of its kind. Emphasis has also been given on the subclassification, differential diagnosis and prognostic antibody factors determining the outcome of DLBCL. PMID:24959047

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

    PubMed

    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. PMID:27367476

  15. [Mechanism of inhibiting the cell growth in diffuse large B-cell lymphoma by valproic acid combined with temsirolimus].

    PubMed

    Zheng, Zhong; Zhao, Yan; Dong, Li-Hua; Wang, Li; Cheng, Shu; Zhao, Wei-Li

    2013-12-01

    The aim of this study was to illustrate the mechanism of inhibiting the cell growth in diffuse large B-cell lymphoma by histone deacetylase inhibitor valproic acid (VPA) combined with mTOR inhibitor temsirolimus (TEM). MTT assay and Wright's stain were used to assess cell growth inhibition and to detect the cell morphological changes respectively. The cell apoptosis, cell cycle and cell autophagy were determined by flow cytometry. Ultrastructure changes were confirmed by electron microscopy. Protein changes were detected by Western blot. The results showed that both VPA and TEM alone inhibited cell proliferation and the effect was more obvious in the combination group. VPA combined with TEM induced cell arrest in G0/G1 phase and upregulated the expression of autophagy-related protein LC3, without cell apoptosis. Moreover, typical autophagosomes were observed, further confirming the presence of autophagy. Western blot showed the changes of proteins involved in autophagy signaling pathway. VPA decreased HDAC1 and HDAC3 expression and increased histone acetylation, suggesting that VPA also affected lymphoma cell proliferation through epigenetic modification. It is concluded that the combined treatment of VPA and TEM induces cell cycle arrest and cell autophagy, which provides a new clue for their clinical application in diffuse large B-cell lymphoma. PMID:24370026

  16. Sclerosing encapsulating peritonitis (abdominal cocoon) associated with liver cirrhosis and diffuse large B-cell lymphoma: autopsy case.

    PubMed

    Yamada, Sohsuke; Tanimoto, Akihide; Matsuki, Yasumasa; Hisada, Yuji; Sasaguri, Yasuyuki

    2009-09-01

    A case of sclerosing encapsulating peritonitis (SEP) associated with liver cirrhosis (LC) and complicated by diffuse large B-cell lymphoma (DLBCL) is reported herein. A 49-year-old Japanese man had undergone peritoneo-venous shunt against refractory ascites due to hepatitis C virus-positive uncompensated LC for 2 years. After he received a diagnosis of DLBCL of the left neck lymph node 3 months before his death, palliative care was given because of his poor general condition. He developed severe abdominal distention and pain over 1 week and was found to have marked ascites and whole bowel lumped together on abdominal CT. At autopsy, the peritoneum was covered with a thick white membrane and the bowel could not be distinguished, which was macroscopically characterized by a cocoon-like appearance. Histology indicated a proliferation of diffusely thickened or hyalinized fibrocollagenous tissue in the entire peritoneum with a slight chronic inflammatory infiltrate and without remarkable change of mucosa. A diagnosis of SEP, also known as abdominal cocoon, was established based on these features. Additionally, in the abdominal cavity, a large amount of serous ascites and multiple peritoneal nodules or masses involved by DLBCL were recognized. To the authors' knowledge this is the first case report of SEP associated with LC and complicated by the invasion of DLBCL in the abdominal cavity. PMID:19712139

  17. miR-4284 and miR-4484 as Putative Biomarkers for Diffuse Large B-Cell Lymphoma

    PubMed Central

    Tamaddon, Gholamhossein; Geramizadeh, Bita; Karimi, Mohammad Hossein; Mowla, Seyed Javad; Abroun, Said

    2016-01-01

    Diffuse large B-cell lymphoma is the most common type of non-Hodgkin lymphoma. MicroRNAs (miRNAs) are endogenous small RNA, which can regulate gene expression at the post-transcriptional level. MiRNA profiling has shown a great potential as novel diagnostic and prognostic biomarkers. The present study was performed at the Nemazee Teaching Hospital (Shiraz, Iran) from 2011 to 2013. The aim of this study was to assess the deregulation of miRNAs profiles in DLBL against hyperplasic reactive lymph node as a normal. This could serve as a biomarker for DLBL. The miRCURY LNA™ microarray was used on the total RNA, which was extracted from formalin-fixed paraffin-embedded tissue of 24 de novo diffuse large B-cell lymphoma patients and 14 normal lymph nodes. The greatest changes were detected in miR-4284 and miR-4484 level in patient’s lymphoma samples. These miRNAs can act as a diagnostic biomarker for DLBL. PMID:27365556

  18. Island coalescence and diffusion along kinked steps on Cu(0 0 1): Evidence for a large kink Ehrlich Schwoebel barrier

    NASA Astrophysics Data System (ADS)

    Ikonomov, Julian; Starbova, Kirilka; Giesen, Margret

    2007-03-01

    Using temperature-variable scanning tunneling microscopy, we studied the coalescence of vacancy islands on Cu(0 0 1) in ultra-high vacuum. From the temperature dependence of the relaxation of merged vacancy islands to the equilibrium shape we obtain an activation energy of the island coalescence process of 0.76 eV. From that value we deduce an activation energy for the atomic hopping coefficient of E=0.89 eV. Comparing our result with previous STM data on step fluctuations with dominant diffusion along straight step segments ( E=0.68 eV; [M. Giesen, S. Dieluweit, J. Mol. Catal. A: Chem. 216 (2004) 263]) and step fluctuations with kink crossing ( E=0.9 eV; [M. Giesen-Seibert, F. Schmitz, R. Jentjens, H. Ibach, Surf. Sci. 329 (1995) 47]), we conclude that there is a large extra barrier for diffusion of atoms across kinks on Cu(0 0 1) of the order of 0.23 eV. This is the first direct experimental evidence for the existence of a large kink Ehrlich-Schwoebel barrier on Cu(0 0 1).

  19. Knowledge, attitude, and practice of HIV/AIDS-related stigma and discrimination reduction among nursing students in southwest Nigeria

    PubMed Central

    Farotimi, Adekunbi A; Nwozichi, Chinomso Ugochukwu; Ojediran, Tolulope D

    2015-01-01

    Background: One of the reported obstacles to the achievement of universal access to Human Immunodeficiency Virus (HIV) prevention, treatment, care, and support programs includes stigma and discrimination from health workers, particularly nurses. Since nursing students would become future practising nurses and are most likely exposed to caring for people living with HIV/AIDS (PL WHA) during their training, it is of great importance to assess the knowledge, attitude, and practice of student nurses toward the reduction of HIV/AIDS-related stigma and discrimination. Materials and Methods: A descriptive survey research design was used. A total of 150 nursing students were selected using the simple random sampling technique of fish bowl method with replacement. Data were obtained using a self-administered (33-item) validated questionnaire to assess the knowledge, attitude, and practice of student nurses with regard to HIV/AIDS-related stigma and discrimination reduction strategies. Reliability of the tool was tested using Cronbach alpha (R) yielding a reliability value of 0.72. Data collected were analyzed with descriptive statistics of frequencies and percentages. Results: Majority (76.0%) of the respondents were females and 82.7% were married. Respondents were found to have high knowledge (94.0%) of strategies for reducing HIV/AIDS-related stigma and discrimination. Also, 64% had moderate discriminatory attitude, 74% engaged in low discriminatory practice, while 26% engaged in high discriminatory practice. Conclusions: Student nurses had adequate knowledge about strategies for reducing HIV/AIDS-related stigma and discrimination; negative discriminatory attitude toward PLWHA and some form of discriminatory practices exist in participants’ training schools. It is, therefore, recommended that an educational package on reduction of HIV/AIDS-related stigma and discrimination be developed and implemented for the participants. PMID:26793257

  20. ESO Diffuse Interstellar Bands Large Exploration Survey (EDIBLES) - Merging Observations and Laboratory Data

    NASA Technical Reports Server (NTRS)

    Salama, Farid

    2016-01-01

    The Diffuse Interstellar Bands (DIBs) are a set of 500 absorption bands that are detected in the spectra of stars with interstellar clouds in the line of sight. DIBs are found from the NUV to the NIR in the spectra of reddened stars spanning different interstellar environments in our local, and in other galaxies. DIB carriers are a significant part of the interstellar chemical inventory. They are stable and ubiquitous in a broad variety of environments and play a unique role in interstellar physics/chemistry. It has long been realized that the solving of the DIB problem requires a strong synergy between astronomical observations, laboratory astrophysics, and astrophysical modeling of line-of-sights. PAHs are among the molecular species that have been proposed as DIB carriers. We will present an assessment of the PAH-DIB model in view of the progress and the advances that have been achieved over the past years through a series of studies involving astronomical observations of DIBs, laboratory simulation of interstellar analogs for neutrals and ionized PAHs, theoretical calculations of PAH spectra and the modelization of diffuse and translucent interstellar clouds. We will present a summary of what has been learned from these complementary studies, the constraints that can now be derived for the PAHs as DIB carriers in the context of the PAH-DIB model and how these constraints can be applied to the EDIBLES project. The spectra of several neutral and ionized PAHs isolated in the gas phase at low temperature have been measured in the laboratory under experimental conditions that mimic interstellar conditions and are compared with an extensive set of astronomical spectra of reddened, early type stars. The comparisons of astronomical and laboratory data provide upper limits for the abundances of specific neutral PAH molecules and ions along specific lines-of-sight. Something that is not attainable from infrared observations alone. We present the characteristics of the

  1. Methodologies for the Analysis of Instantaneous Lipid Diffusion in MD Simulations of Large Membrane Systems

    PubMed Central

    Chavent, Matthieu; Reddy, Tyler; Goose, Joseph; Dahl, Anna Caroline E.; Stone, John E.; Jobard, Bruno; Sansom, Mark S.P.

    2014-01-01

    Interactions between lipids and membrane proteins play a key role in determining the nanoscale dynamic and structural properties of biological membranes. Molecular dynamics (MD) simulations provide a valuable tool for studying membrane models, complementing experimental approaches. It is now possible to simulate large membrane systems, such as simplified models of bacterial and viral envelope membranes. Consequently, there is a pressing need to develop tools to visualize and quantify the dynamics of these immense systems, which typically are comprised of millions of particles. To tackle this issue, we have developed visual and quantitative analyses of molecular positions and their velocity field using path line, vector field and streamline techniques. This allows us to highlight large, transient flow-like movements of lipids and to better understand crowding within the lipid bilayer. The current study focuses on visualization and analysis of lipid dynamics. However, the methods are flexible and can be readily applied to e.g. proteins and nanoparticles within large complex membranes. The protocols developed here are readily accessible both as a plugin for the molecular visualization program VMD and as a module for the MDAnalysis library. PMID:25341001

  2. Large deviations of the current in a two-dimensional diffusive system

    SciTech Connect

    Perez-Espigares, C.; Pozo, J. J. del; Garrido, P. L.; Hurtado, P. I.

    2011-03-24

    In this notes we study the large deviations of the time-averaged current in the two-dimensional (2D) Kipnis-Marchioro-Presutti model of energy transport when subject to a boundary gradient. We use the tools of hydrodynamic fluctuation theory, supplemented with an appropriate generalization of the additivity principle. As compared to its one-dimensional counterpart, which amounts to assume that the optimal profiles responsible of a given current fluctuation are time-independent, the 2D additivity conjecture requires an extra assumption, i.e. that the optimal, divergence-free current vector field associated to a given fluctuation of the time-averaged current is in fact constant across the system. Within this context we show that the current distribution exhibits in general non-Gaussian tails. The ensuing optimal density profile can be either monotone for small current fluctuations, or non-monotone with a single maximum for large enough current deviations. Furthermore, this optimal profile remains invariant under arbitrary rotations of the current vector, providing a detailed example of the recently introduced Isometric Fluctuation Relation.

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

    PubMed

    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. PMID:20481672

  4. Design Calculations for Gas Flow & Diffusion Behavior in the large Diameter Container & Cask

    SciTech Connect

    PIEPHO, M.G.

    2003-10-21

    This report describes the calculations for the gas behavior in the void volumes or gas spaces of the sludge Large Diameter Container (LDC) and Cask. The objective is to prevent flammable gas conditions in the LDC and Cask gas spaces. This is achieved by the Active Inert Ventilation System (AIVS), which uses argon gas for dilution purposes. With AIVS, the oxygen content is kept below 5 vol% in the LDC, and the hydrogen content is kept below 4 vol% in the Cask before its purge at the KE Basin. After the Cask sweep-through purge with argon at the KE Basin, oxygen is kept below 5% in both the Cask and the LDC. The analysis here assumes that any oxygen generated in the sludge is consumed by the uranium and uranium dioxide (SNF-18133, ''Gas Behavior in Large Diameter Containers (LDCs) During and Following Loading with 105K East Sludge''). Thus, oxygen production from radiolysis is intentionally not included in this report, but hydrogen from radiolysis and from chemical reactions between uranium and water are considered, depending on the scenario being analyzed. The analysis starts immediately after the final decant at K Basin, when argon is assumed to be the only gas in the LDC gas space, except for the normal water vapor. The oxygen ingress is calculated during the disconnecting of the lines hoses from the LDC, during the time that air is surrounding the LDC with two NucFil-type filters in place after the disconnect, before the Cask is sealed, and, finally, during the sweep-through Cask purge. Dissolution of oxygen from water due to increasing sludge temperatures (mainly during hot transport to the T Plant) is also included.

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

    NASA Astrophysics Data System (ADS)

    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.

  6. Immunoproliferative Small Intestinal Disease Associated with Overwhelming Polymicrobial Gastrointestinal Infection with Transformation to Diffuse Large B-cell Lymphoma.

    PubMed

    Ewers, Evan C; Sheffler, Robert L; Wang, James; Ngauy, Viseth

    2016-05-01

    Immunoproliferative small intestinal disease (IPSID) is an extra-nodal B-cell lymphoma most commonly described in the Mediterranean, Africa, and Asia. It is associated with poverty and poor sanitation, and is rarely encountered in developed countries. A 26-year-old previously healthy, Marshallese male was transferred to our facility with a 6-month history of watery diarrhea, weakness, and cachexia refractory to multiple short courses of oral antibiotics. Stool cultures grew Campylobacter jejuni and Vibrio fluvialis. Endoscopic evaluation showed histologic evidence of Helicobacter pylori gastritis and gross evidence of whipworm infection found in the colon. Mesenteric lymph node biopsy cultures grew Escherichia coli. Histopathology and immunohistochemical stains of the small intestine were consistent with IPSID. He subsequently transformed to diffuse large B-cell lymphoma (DLBCL) with tonsillar involvement despite treatment with rituximab and an extended course of antibiotics. Systemic chemotherapy with six cycles of rituximab, cyclophosphamide, vincristine, doxorubicin, prednisone, and lenalidomide, resulted in remission of his diffuse B cell lymphoma. This case is illustrative of IPSID developing in a previously healthy individual due to overwhelming polymicrobial gastrointestinal infection by C. jejuni and other enteric pathogens with subsequent transformation to an aggressive DLBCL. IPSID should be considered in residents of developing countries presenting with refractory chronic diarrhea, weight loss, and mesenteric lymphadenopathy. PMID:26903604

  7. Design Calculations for Gas Flow & Diffusion Behavior in the Large Diameter Container & Cask

    SciTech Connect

    PIEPHO, M.G.

    2003-11-06

    This report describes the calculations for the gas behavior in the void volumes or gas spaces of the sludge Large Diameter Container (LDC) and Cask. The objective is to prevent flammable gas conditions in the LDC and Cask gas spaces. This is achieved by the Active Inert Ventilation System (AIVS), which uses argon gas for dilution purposes. With AIVS, the oxygen content is kept below 4 to 5 vol% in the LDC, and the hydrogen content is kept below 4 vol% in the Cask before its purge at the KE Basin. After the Cask sweep-through purge with argon at the KE Basin, oxygen stays below 4 to 5% in the LDC until two LDC ports are opened at T Plant. The oxygen content stays below 4% in the Cask until the Cask lid is opened at T Plant. The analysis here assumes that any oxygen generated in the sludge is consumed by the uranium and uranium dioxide (SNF-18133, ''Gas Behavior in Large Diameter Containers (LDCs) During and Following Loading with 105K East Sludge''). Thus, oxygen production from radiolysis is not included in this report, but hydrogen from radiolysis and from chemical reactions between uranium and water are considered, depending on the scenario being analyzed. The analysis starts immediately after the final decant at K Basin, when argon is assumed to be the only gas in the LDC gas space, except for the normal water vapor. The oxygen ingress is calculated during the disconnecting of the lined hoses from the LDC, during the time that air is surrounding the LDC with two NucFil-type filters in place after the disconnect, before the Cask is sealed, and, finally, during the sweep-through Cask purge at the KE Basin. Dissolution of oxygen from water due to increasing sludge temperatures (mainly during hot transport to the T Plant) is also included. The analysis includes the gas behavior during the T-Plant operations, which include the venting after the LDC/Cask are received at T Plant, the Cask sweep-through purge, the LDC purge with forced argon delivery into the LDC with 1

  8. A nonlinear, transient finite element method for coupled solvent diffusion and large deformation of hydrogels

    NASA Astrophysics Data System (ADS)

    Bouklas, Nikolaos; Landis, Chad M.; Huang, Rui

    2015-06-01

    Hydrogels are capable of coupled mass transport and large deformation in response to external stimuli. In this paper, a nonlinear, transient finite element formulation is presented for initial boundary value problems associated with swelling and deformation of hydrogels, based on a nonlinear continuum theory that is consistent with classical theory of linear poroelasticity. A mixed finite element method is implemented with implicit time integration. The incompressible or nearly incompressible behavior at the initial stage imposes a constraint to the finite element discretization in order to satisfy the Ladyzhenskaya-Babuska-Brezzi (LBB) condition for stability of the mixed method, similar to linear poroelasticity as well as incompressible elasticity and Stokes flow; failure to choose an appropriate discretization would result in locking and numerical oscillations in transient analysis. To demonstrate the numerical method, two problems of practical interests are considered: constrained swelling and flat-punch indentation of hydrogel layers. Constrained swelling may lead to instantaneous surface instability for a soft hydrogel in a good solvent, which can be regulated by assuming a stiff surface layer. Indentation relaxation of hydrogels is simulated beyond the linear regime under plane strain conditions, in comparison with two elastic limits for the instantaneous and equilibrium states. The effects of Poisson's ratio and loading rate are discussed. It is concluded that the present finite element method is robust and can be extended to study other transient phenomena in hydrogels.

  9. Case Report of Diffuse Large B Cell Lymphoma of Uterine Cervix Treated at a Semiurban Cancer Centre in North India

    PubMed Central

    Sridhar, Epari

    2016-01-01

    Lymphoma of the uterine cervix is very rare. We report a case of diffuse large B cell lymphoma (DLBCL) involving the uterine cervix treated at a newly commissioned semiurban cancer centre in north India in 2015. Data for this study was obtained from the hospital electronic medical records and the patient's case file. We also reviewed published case reports of uterine and cervical lymphoma involving forty-one patients. We treated a case of stage IV DLBCL cervix with six cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) and intrathecal methotrexate followed by consolidation with radiotherapy. The patient showed complete response to chemotherapy. We conclude that, in advanced stage lymphoma involving uterus and cervix, combination of chemotherapy and radiotherapy is effective in short term. PMID:27597906

  10. Coexistent rearrangements of c-MYC, BCL2, and BCL6 genes in a diffuse large B-cell lymphoma.

    PubMed

    Ueda, Chiyoko; Nishikori, Momoko; Kitawaki, Toshio; Uchiyama, Takashi; Ohno, Hitoshi

    2004-01-01

    We present a patient with stage III de novo diffuse large B-cell lymphoma. The lymphoma cells showed mature B-cell immunophenotype but lacked surface immunoglobulin (Ig) expression. Long-distance and long-distance inverse polymerase chain reaction assays to detect the oncogene/Ig gene rearrangement revealed that the cells carried 3 independent fusion genes, namely, c-MYC/Ig heavy chain gene (IgH), BCL2/IgH, and Ig lambda light chain gene/BCL6. Thus, the lymphoma cells concurrently carried t(8;14)(q24;q32), t(14;18)(q32;q21), and t(3;22)(q27;q11), which developed in association with class switching, V/D/J recombination, and somatic hypermutation, respectively. The lymphoma responded to chemoradiotherapy, and the patient has been well for 2 years, suggesting that multiple oncogene rearrangements may not necessarily be associated with poor clinical outcome. PMID:14979479

  11. The Role of Autologous Stem Cell Transplantation in the Treatment of Diffuse Large B-Cell Lymphoma

    PubMed Central

    Gunnellini, Marco; Emili, Rita; Coaccioli, Stefano; Liberati, Anna Marina

    2012-01-01

    Diffuse large B-cell non-Hodgkin's lymphoma (DLBCL) accounting for approximately 30% of new lymphoma diagnoses in adult patients. Complete remissions (CRs) can be achieved in 45% to 55% of patients and cure in approximately 30–35% with anthracycline-containing combination chemotherapy. The ageadjusted IPI (aaIPI) has been widely employed, particularly to “tailor” more intensive therapy such as high-dose therapy (HDT) with autologous hemopoietic stem cell rescue (ASCT). IPI, however, has failed to reliably predict response to specific therapies. A subgroup of young patients with poor prognosis exists. To clarify the role of HDT/ASCT combined with rituximab in the front line therapy a longer follow-up and randomized studies are needed. The benefit of HDT/ASCT for refractory or relapsed DLBCL is restricted to patients with immunochemosensitive disease. Currently, clinical and biological research is focused to improve the curability of this setting of patients, mainly young. PMID:22312366

  12. Modification of commercial NaY zeolite to give high water diffusivity and adsorb a large amount of water.

    PubMed

    Katoh, Masahiro; Kimura, Michisato; Sugino, Mao; Horikawa, Toshihide; Nakagawa, Keizo; Sugiyama, Shigeru

    2015-10-01

    By using NaY zeolites as desiccant materials, commercial NaY zeolite was alkali treated with 1 M NaOH aqueous solution and then Mg(2+) ion-exchanged by 0.5 M Mg(NO3)2 aqueous solution. Alkali treatment (AT) of NaY zeolite removed silicon atoms selectivity from the framework of Y-type zeolite and enhanced water diffusivity of Y-type zeolite. On the other hand, Mg(2+) ion-exchange of NaY zeolite increased the amount of water adsorbed. Prepared Y-AT-Mg zeolite had both water adsorption velocity and a large difference of water adsorbed amount between adsorption at 30 °C and desorption at 100 °C. PMID:26072446

  13. Fever and arthralgia as the initial symptoms of primary bone marrow diffuse large B-cell lymphoma: A case report

    PubMed Central

    REN, SAISAI; TAO, YANLING; JIA, LU; CHENG, PANPAN; ZHANG, JILEI; ZHANG, HAO

    2016-01-01

    Primary bone marrow diffuse large B-cell lymphoma (DLBCL) is rare, and only a few cases have been reported. Fever and arthralgia as the initial symptom are extremely rare; however, awareness must be made of this presentation. The current study describes the clinical and pathological findings of a 41-year-old man affected by fever and arthralgia. Blood tests revealed leukopenia and anemia. Multiple bone marrow biopsies were conducted and confirmed the diagnosis of primary bone marrow DLBCL. Primary bone marrow DLBCL is a rare and frequently misdiagnosed subset of non-Hodgkin's lymphoma. The current case demonstrates that utility of bone marrow biopsy for diagnosis should not be ignored, and that repeated bone marrow punctures in multiple locations may be necessary. PMID:27123129

  14. MAGE-A3 expression is an adverse prognostic factor in diffuse large B-cell lymphoma.

    PubMed

    Olarte, Irma; Martinez, Adolfo; Ramos-Peñafiel, Christian; Castellanos-Sinco, Humberto; Zamora, Jorge; Collazo-Jaloma, Juan; Gutiérrez, Mario; Gutiérrez-Kobeh, Laila; Chavez-Olmos, Pedro; Manzanilla, Hugo; Garrido-Guerrero, Efraín; Ordoñez-Razo, Rosa M; Miranda, Enrique I

    2011-11-01

    This study evaluates the prognostic value of MAGE-A3 expression in 28 diffuse large B-cell lymphoma (DLBCL) patients. A significant association was observed between MAGE-A3 expressions, assessed by quantitative real-time RT-polymerase chain reaction (PCR), with advanced stages of disease (P < 0.05). Elevated serum lactate dehydrogenase (LDH) levels and International Prognostic Index (IPI) score were significantly higher in MAGE-A3-positive patients (P = 0.025 and P = 0.004, respectively). Expression of MAGE-A3 was associated with poor response to treatment and a significantly shorter overall survival (P < 0.001). Our data address new information in the association of MAGE-A3 expression and poor prognosis in DLBCL patients. PMID:22183072

  15. Validity of reduced radiation dose for localized diffuse large B-cell lymphoma showing a good response to chemotherapy.

    PubMed

    Koiwai, Keiichiro; Sasaki, Shigeru; Yoshizawa, Eriko; Ina, Hironobu; Fukazawa, Ayumu; Sakai, Katsuya; Ozawa, Takesumi; Matsushita, Hirohide; Kadoya, Masumi

    2014-03-01

    To evaluate the validity of a decrease in the radiation dose for patients who were good responders to chemotherapy for localized diffuse large B-cell lymphoma (DLBCL), 91 patients with localized DLBCL who underwent radiotherapy after multi-agent chemotherapy from 1988-2008 were reviewed. Exclusion criteria were as follows: central nervous system or nasal cavity primary site, or Stage II with bulky tumor (≥10 cm). Of these patients, 62 were identified as good responders to chemotherapy. They were divided into two groups receiving either a higher or a lower radiation dose (32-50.4 Gy or 15-30.6 Gy, respectively). There were no statistically significant differences between the lower and higher dose groups in progression-free survival, locoregional progression-free survival or overall survival. Adaptation of decreased radiation dose may be valid for localized DLBCL patients who show a good response to chemotherapy. PMID:24187329

  16. Case Report of Diffuse Large B Cell Lymphoma of Uterine Cervix Treated at a Semiurban Cancer Centre in North India.

    PubMed

    Sharma, Vibhor; Dora, Tapas; Patel, Mehul; Sancheti, Sankalp; Sridhar, Epari

    2016-01-01

    Lymphoma of the uterine cervix is very rare. We report a case of diffuse large B cell lymphoma (DLBCL) involving the uterine cervix treated at a newly commissioned semiurban cancer centre in north India in 2015. Data for this study was obtained from the hospital electronic medical records and the patient's case file. We also reviewed published case reports of uterine and cervical lymphoma involving forty-one patients. We treated a case of stage IV DLBCL cervix with six cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) and intrathecal methotrexate followed by consolidation with radiotherapy. The patient showed complete response to chemotherapy. We conclude that, in advanced stage lymphoma involving uterus and cervix, combination of chemotherapy and radiotherapy is effective in short term. PMID:27597906

  17. Primary Diffuse Large B-cell Lymphoma Arising in the Tongue Accompanied by Ataxia-telangiectasia: A Case Report

    PubMed Central

    Kaneoya, Ayano; Mochizuki, Yumi; Harada, Hiroyuki

    2015-01-01

    Ataxia-telangiectasia (AT) is a rare autosomal recessive disorder that is characterized by progressive cerebellar ataxia, telangiectasia, immunodeficiency, and a predisposition to leukemia/lymphoma. Here we report a rare case of lymphoma of the tongue accompanied by AT. Tumour extirpation was performed and diffuse large B-cell lymphoma was diagnosed following pathologic examination. A whole-body survey showed no other enlarged lymph nodes or tumour. The female patient then received a modified dosage of COPAD (cyclophosphamide, vinblastine, pirarubicin, and prednisolone) plus rituximab to avoid severe complications. As of follow-up after 3 years and 5 months, she remains in complete remission. Patients showing AT need careful surveillance and long-term continuous follow-up. PMID:26266230

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

    PubMed

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

    2014-06-01

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

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

    PubMed Central

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

    2014-01-01

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

  20. Prediction of survival of diffuse large B-cell lymphoma patients via the expression of three inflammatory genes.

    PubMed

    Zhao, Shuangtao; Bai, Nan; Cui, Jianlin; Xiang, Rong; Li, Na

    2016-08-01

    Currently, several gene-expression signatures that were used to predict survival of diffuse large B-cell lymphoma (DLBCL) patients, showed a restriction on the practical work for lack of convenient operation. In this study, we screened inflammatory genes whose expression correlated with survival of DLBCL and established a predictive model including IL6, IL1A and CSF3 through multivariate Cox regression based on the expression of these three genes. We validated the model at protein level in our clinical serum cohort composed of 101 patients of DLBCL and 50 healthy controls and 534 DLBCL patients at mRNA level from three independent Gene Expression Omnibus (GEO) data sets. We found our model to be independent of the International Prognostic Index (IPI), moreover, it can augment the predictive power of IPI. In summary, our three-gene model is sufficient to predict survival of DLBCL patients via measuring the concentration of three inflammatory cytokines in peripheral blood. PMID:27394196

  1. Machine Learning-based Classification of Diffuse Large B-cell Lymphoma Patients by Their Protein Expression Profiles

    PubMed Central

    Deeb, Sally J.; Tyanova, Stefka; Hummel, Michael; Schmidt-Supprian, Marc; Cox, Juergen; Mann, Matthias

    2015-01-01

    Characterization of tumors at the molecular level has improved our knowledge of cancer causation and progression. Proteomic analysis of their signaling pathways promises to enhance our understanding of cancer aberrations at the functional level, but this requires accurate and robust tools. Here, we develop a state of the art quantitative mass spectrometric pipeline to characterize formalin-fixed paraffin-embedded tissues of patients with closely related subtypes of diffuse large B-cell lymphoma. We combined a super-SILAC approach with label-free quantification (hybrid LFQ) to address situations where the protein is absent in the super-SILAC standard but present in the patient samples. Shotgun proteomic analysis on a quadrupole Orbitrap quantified almost 9,000 tumor proteins in 20 patients. The quantitative accuracy of our approach allowed the segregation of diffuse large B-cell lymphoma patients according to their cell of origin using both their global protein expression patterns and the 55-protein signature obtained previously from patient-derived cell lines (Deeb, S. J., D'Souza, R. C., Cox, J., Schmidt-Supprian, M., and Mann, M. (2012) Mol. Cell. Proteomics 11, 77–89). Expression levels of individual segregation-driving proteins as well as categories such as extracellular matrix proteins behaved consistently with known trends between the subtypes. We used machine learning (support vector machines) to extract candidate proteins with the highest segregating power. A panel of four proteins (PALD1, MME, TNFAIP8, and TBC1D4) is predicted to classify patients with low error rates. Highly ranked proteins from the support vector analysis revealed differential expression of core signaling molecules between the subtypes, elucidating aspects of their pathobiology. PMID:26311899

  2. Prognostic value of interim 18F-FDG PET/CT in diffuse large B-cell lymphoma

    PubMed Central

    Ying, Zhitao; Wang, Xuejuan; Song, Yuqin; Zheng, Wen; Wang, Xiaopei; Xie, Yan; Lin, Ningjing; Tu, Meifeng; Ping, Lingyan; Liu, Weiping; Deng, Lijuan; Zhang, Chen; Yang, Zhi

    2013-01-01

    Objective Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease. The prognostic factor currently used is not accurate enough to predict the outcomes of patients with DLBCL. The prognostic significance of interim PET/CT in DLBCL remains controversial. The aim of this study is to determine the predictive value of interim 18F-FDG PET/CT after first-line treatment in patients with DLBCL. Methods Thirty-two patients with DLBCL underwent baseline, interim and post-treatment 18F-FDG PET/CT scans. Imaging results were analyzed for the survival of patients via software SPSS 13.0, retrospectively. Results Thirty-one of the 32 patients were treated with R-CHOP regimen, and interim 18F-FDG PET/CT of 24 patients was performed after 2 cycles of treatment. After a median follow-up period of 16.7 months, the 2-year progression-free survival (PFS) rates were significantly different between the groups above and below SUVmax cut-off value of 2.5 (P=0.039). No significant differences were found in the 2-year PFS rates if SUVmax cut-off values were set as 2.0 and 3.0, respectively (P=0.360; P=0.113). Conclusions Interim PET/CT could predict the prognosis of DLBCL patients with the SUVmax cut-off value of 2.5, but more clinical data should be concluded to confirm this conclusion. Key Words Fludeoxyglucose F18; lymphoma; large cell; diffuse; prognosis; standard utility value PMID:23372347

  3. Machine Learning-based Classification of Diffuse Large B-cell Lymphoma Patients by Their Protein Expression Profiles.

    PubMed

    Deeb, Sally J; Tyanova, Stefka; Hummel, Michael; Schmidt-Supprian, Marc; Cox, Juergen; Mann, Matthias

    2015-11-01

    Characterization of tumors at the molecular level has improved our knowledge of cancer causation and progression. Proteomic analysis of their signaling pathways promises to enhance our understanding of cancer aberrations at the functional level, but this requires accurate and robust tools. Here, we develop a state of the art quantitative mass spectrometric pipeline to characterize formalin-fixed paraffin-embedded tissues of patients with closely related subtypes of diffuse large B-cell lymphoma. We combined a super-SILAC approach with label-free quantification (hybrid LFQ) to address situations where the protein is absent in the super-SILAC standard but present in the patient samples. Shotgun proteomic analysis on a quadrupole Orbitrap quantified almost 9,000 tumor proteins in 20 patients. The quantitative accuracy of our approach allowed the segregation of diffuse large B-cell lymphoma patients according to their cell of origin using both their global protein expression patterns and the 55-protein signature obtained previously from patient-derived cell lines (Deeb, S. J., D'Souza, R. C., Cox, J., Schmidt-Supprian, M., and Mann, M. (2012) Mol. Cell. Proteomics 11, 77-89). Expression levels of individual segregation-driving proteins as well as categories such as extracellular matrix proteins behaved consistently with known trends between the subtypes. We used machine learning (support vector machines) to extract candidate proteins with the highest segregating power. A panel of four proteins (PALD1, MME, TNFAIP8, and TBC1D4) is predicted to classify patients with low error rates. Highly ranked proteins from the support vector analysis revealed differential expression of core signaling molecules between the subtypes, elucidating aspects of their pathobiology. PMID:26311899

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

    PubMed

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

    2015-01-01

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

  5. Definition of MYC genetic heteroclonality in diffuse large B-cell lymphoma with 8q24 rearrangement and its impact on protein expression.

    PubMed

    Valera, Alexandra; Epistolio, Samantha; Colomo, Lluis; Riva, Alice; Balagué, Olga; Dlouhy, Ivan; Tzankov, Alexandar; Bühler, Marco; Haralambieva, Eugenia; Campo, Elias; Soldini, Davide; Mazzucchelli, Luca; Martin, Vittoria

    2016-08-01

    MYC rearrangement can be detected in a subgroup of diffuse large B-cell lymphoma characterized by unfavorable prognosis. In contrast to Burkitt lymphoma, the correlation between MYC rearrangement and MYC protein expression in diffuse large B-cell lymphoma is less clear, as approximately one-third of rearranged cases show negative or low expression by immunohistochemistry. To better understand whether specific characteristics of the MYC rearrangement may influence its protein expression, we investigated 43 de novo diffuse large B-cell lymphoma positive for 8q24 rearrangement by FISH, using 14 Burkitt lymphoma for comparison. Different cell populations (clones), breakpoints (classical vs non-classical FISH patterns), partner genes (IGH vs non-IGH) and immunostaining were detected and analyzed using computerized image systems. In a subgroup of diffuse large B-cell lymphoma, we observed different clones within the same tumor distinguishing the founder clone with MYC rearrangement alone from other subclones, carrying MYC rearrangement coupled with loss/extra copies of derivatives/normal alleles. This picture, which we defined MYC genetic heteroclonality, was found in 42% of cases and correlated to negative MYC expression (P=0.026). Non-classical FISH breakpoints were detected in 16% of diffuse large B-cell lymphoma without affecting expression (P=0.040). Non-IGH gene was the preferential partner of rearrangement in those diffuse large B-cell lymphoma showing MYC heteroclonality (P=0.016) and/or non-classical FISH breakpoints (P=0.058). MYC heteroclonality was not observed in Burkitt lymphoma and all cases had positive MYC expression. Non-classical FISH MYC breakpoint and non-IGH partner were found in 29 and 20% of Burkitt lymphoma, respectively. In conclusion, MYC genetic heteroclonality is a frequent event in diffuse large B-cell lymphoma and may have a relevant role in modulating MYC expression. PMID:27125356

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

    SciTech Connect

    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.

    2014-01-28

    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.

  7. Creating social spaces to tackle AIDS-related stigma: reviewing the role of church groups in Sub-Saharan Africa.

    PubMed

    Campbell, C; Skovdal, M; Gibbs, A

    2011-08-01

    An expanding body of literature explores the role of African church groups in facilitating or hindering the support of people living with AIDS and challenging or contributing to HIV/AIDS-related stigma. Treating church groups as social spaces in which HIV/AIDS-related stigma may potentially be challenged, we systematically review this literature, identifying five themes that highlight the complex and contradictory role of the church as a potential agent of health-enhancing social change. In many ways the church perpetuates HIV/AIDS-related stigma through (i) moralistic attitudes and (ii) its reinforcement of conservative gender ideologies. However some churches have managed move towards action that makes a more positive contribution to HIV/AIDS management through (iii) promoting various forms of social control for HIV prevention, (iv) contributing to the care and support of the AIDS-affected and (v) providing social spaces for challenging stigmatising ideas and practices. We conclude that church groups, including church leadership, can play a key role in facilitating or hindering the creation of supportive social spaces to challenge stigma. Much work remains to be done in developing deeper understandings of the multi-layered factors that enable some churches, but not others, to respond effectively to HIV/AIDS. PMID:20668927

  8. Creating Social Spaces to Tackle AIDS-Related Stigma: Reviewing the Role of Church Groups in Sub-Saharan Africa

    PubMed Central

    Skovdal, M.; Gibbs, A.

    2012-01-01

    An expanding body of literature explores the role of African church groups in facilitating or hindering the support of people living with AIDS and challenging or contributing to HIV/AIDS-related stigma. Treating church groups as social spaces in which HIV/AIDS-related stigma may potentially be challenged, we systematically review this literature, identifying five themes that highlight the complex and contradictory role of the church as a potential agent of health-enhancing social change. In many ways the church perpetuates HIV/AIDS-related stigma through (i) moralistic attitudes and (ii) its reinforcement of conservative gender ideologies. However some churches have managed move towards action that makes a more positive contribution to HIV/AIDS management through (iii) promoting various forms of social control for HIV prevention, (iv) contributing to the care and support of the AIDS-affected and (v) providing social spaces for challenging stigmatising ideas and practices. We conclude that church groups, including church leadership, can play a key role in facilitating or hindering the creation of supportive social spaces to challenge stigma. Much work remains to be done in developing deeper understandings of the multi-layered factors that enable some churches, but not others, to respond effectively to HIV/AIDS. PMID:20668927

  9. Belief in AIDS-Related Conspiracy Theories and Mistrust in the Government: Relationship With HIV Testing Among At-Risk Older Adults

    PubMed Central

    Ford, Chandra L.

    2013-01-01

    Purpose: One in 4 persons living with HIV/AIDS is an older adult (age 50 or older); unfortunately, older adults are disproportionately diagnosed in late stages of HIV disease. Psychological barriers, including belief in AIDS-related conspiracy theories (e.g., HIV was created to eliminate certain groups) and mistrust in the government, may influence whether adults undergo HIV testing. We examined relationships between these factors and recent HIV testing among at-risk, older adults. Design and Methods: This was a cross-sectional study among older adults enrolled in a large venue–based study. None had a previous diagnosis of HIV/AIDS; all were seeking care at venues with high HIV prevalence. We used multiple logistic regression to estimate the associations between self-reported belief in AIDS-related conspiracy theories, mistrust in the government, and HIV testing performed within the past 12 months. Results: Among the 226 participants, 30% reported belief in AIDS conspiracy theories, 72% reported government mistrust, and 45% reported not undergoing HIV testing within the past 12 months. Belief in conspiracy theories was positively associated with recent HIV testing (adjusted odds ratio [OR] = 1.94, 95% confidence interval [CI] = 1.05–3.60), whereas mistrust in the government was negatively associated with testing (OR = 0.43, 95% CI = 0.26–0.73). Implications: Psychological barriers are prevalent among at-risk older adults seeking services at venues with high HIV prevalences and may influence HIV testing. Identifying particular sources of misinformation and mistrust would appear useful for appropriate targeting of HIV testing strategies. PMID:23362210

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

    NASA Astrophysics Data System (ADS)

    An, Yonghao; Jiang, Hanqing

    2013-10-01

    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.

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

    PubMed

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

    2016-06-01

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

  12. Lunar water migration in the interval between large impacts: Heterogeneous delivery to Permanently Shadowed Regions, fractionation, and diffusive barriers

    NASA Astrophysics Data System (ADS)

    Moores, John E.

    2016-01-01

    The migration of water molecules across the lunar surface from sources sufficiently small, so as to not generate a transient collisional atmosphere, was examined using a Monte Carlo simulation. Previous work using similar models is extended by examining a realistic distribution of large south polar Permanently Shadowed Regions (PSRs) to examine the heterogeneities observed in their water content—frost in Haworth and the nearby lowlands, but not in neighboring Shoemaker, and anomalously high hydrogen abundances from neutron data—and to determine how the pattern of water delivery can be distinguished from that predicted for transient collisional atmospheres. While the Haworth lowlands were seen to accumulate 3.9 times as much water as Shoemaker, the additional water delivered to Haworth crater was only 47% greater than Shoemaker, possibly due to shielding by Faustini and the lowlands. This relatively small difference is likely inadequate to explain the difference in frosting. More broadly, latitudinal trends in delivery dominate over meridional trends. Despite the heterogeneity in water delivery, fractionation effects from ballistic migration were small for the PSRs with equal D/H ratios seen in all PSRs within confidence limits. Finally, a diffusive barrier was observed starting at approximately 15° from each pole that hampers the poleward progress of equatorial particles. This barrier is the result of a reduction in the migration diffusivity from 1.0 × 107 m2 s-1 near the equator to 5.5 × 105 m2 s-1 within 10° of the pole and finally to 6.8 × 103 m2 s-1 within 4° of the pole.

  13. 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.

    PubMed

    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. PMID:25704629

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

    PubMed Central

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

    2016-01-01

    We examined treatment with or without anthracyclines in 72 eldery diffuse large B-cell lymphoma patients (age ≥ 65 years) in a retrospective cohort analysis. Factors leading to treatment without an anthracycline included age and ejection fraction, whereas markers of tolerability were similar between groups. This study highlights the details of anthracycline tolerability in elderly lymphoma patients. Introduction Although diffuse large B-cell lymphoma (DLBCL) can be cured with rituximab and anthracycline-based therapy, within the elderly population there are additional factors to consider in selecting a treatment regimen including comorbid conditions, decreased drug metabolism, decreased hematologic reserve, reduced performance status, and regimen-related toxicity. Patients and Methods We performed a retrospective cohort analysis of patients with DLBCL aged ≥ 65 years at time of diagnosis treated with either an anthracycline-containing regimen (ACR; n = 59) or a non-ACR (n = 13) to assess factors that led to treatment selection, tolerability, and outcomes. Results The mean age was 73 years in the ACR and 77 years in the non-ACR group (P = .009), and median left ventricular ejection fraction (LVEF) at diagnosis was 60% in the ACR group and 45% in the non-ACR group (P < .001). With an ACR, elderly DLBCL patients had a median overall survival of 28 months and a 2-year progression-free survival (PFS) of 64%. After an ACR, 14 patients [24%] (out of 59 total patients) had a decrease in LVEF, 7 patients [15%] (% is based off of those who we had the data collected, so this is out of 45 with this specific data) required a dose reduction of the anthracycline, and 15 patients [33%] (% is based off of those who we had the data collected, so this is out of 45 with this specific data) could not complete the regimen as planned. Hospitalization due to toxicity occurred in 20 patients [44%] (% is based off of those who we had the data collected, so this is out of 45 with data

  15. Genome-Wide Association Study of Event-Free Survival in Diffuse Large B-Cell Lymphoma Treated With Immunochemotherapy

    PubMed Central

    Ghesquieres, Hervé; Slager, Susan L.; Jardin, Fabrice; Veron, Amelie S.; Asmann, Yan W.; Maurer, Matthew J.; Fest, Thierry; Habermann, Thomas M.; Bene, Marie C.; Novak, Anne J.; Mareschal, Sylvain; Haioun, Corinne; Lamy, Thierry; Ansell, Stephen M.; Tilly, Herve; Witzig, Thomas E.; Weiner, George J.; Feldman, Andrew L.; Dogan, Ahmet; Cunningham, Julie M.; Olswold, Curtis L.; Molina, Thierry Jo; Link, Brian K.; Milpied, Noel; Cox, David G.; Salles, Gilles A.; Cerhan, James R.

    2015-01-01

    Purpose We performed a multistage genome-wide association study to identify inherited genetic variants that predict outcome in diffuse large B-cell lymphoma patients treated with immunochemotherapy. Methods We conducted a meta-analysis of two genome-wide association study data sets, one from the LNH2003B trial (N = 540), a prospective clinical trial from the Lymphoma Study Association, and the other from the Molecular Epidemiology Resource study (N = 312), a prospective observational study from the University of Iowa–Mayo Clinic Lymphoma Specialized Program of Research Excellence. Top single nucleotide polymorphisms were then genotyped in independent cohorts of patients from the Specialized Program of Research Excellence (N = 391) and the Groupe Ouest-Est des Leucémies Aiguës et Maladies du Sang (GOELAMS) -075 randomized trial (N = 294). We calculated the hazard ratios (HRs) and 95% CIs for event-free survival (EFS) and overall survival (OS) using a log-additive genetic model with adjustment for age, sex, and age-adjusted International Prognostic Index. Results In a meta-analysis of the four studies, the top loci for EFS were marked by rs7712513 at 5q23.2 (near SNX2 and SNCAIP; HR, 1.39; 95% CI, 1.23 to 1.57; P = 2.08 × 10−7), and rs7765004 at 6q21 (near MARCKS and HDAC2; HR, 1.38; 95% CI, 1.22 to 1.57; P = 7.09 × 10−7), although they did not reach conventional genome-wide significance (P = 5 × 10−8). Both rs7712513 (HR, 1.49; 95% CI, 1.29 to 1.72; P = 3.53 × 10−8) and rs7765004 (HR, 1.47; 95% CI, 1.27 to 1.71; P = 5.36 × 10−7) were also associated with OS. In exploratory analyses, a two–single nucleotide polymorphism risk score was highly predictive of EFS (P = 1.78 × 10−12) and was independent of treatment, IPI, and cell-of-origin classification. Conclusion Our study provides encouraging evidence for associations between loci at 5q23.2 and 6q21 with EFS and OS in patients with diffuse large B-cell lymphoma treated with immunochemotherapy

  16. Constitutive activation of the DNA damage response pathway as a novel therapeutic target in diffuse large B-cell lymphoma

    PubMed Central

    Derenzini, Enrico; Agostinelli, Claudio; Imbrogno, Enrica; Iacobucci, Ilaria; Casadei, Beatrice; Brighenti, Elisa; Righi, Simona; Fuligni, Fabio; Di Rorà, Andrea Ghelli Luserna; Ferrari, Anna; Martinelli, Giovanni; Pileri, Stefano; Zinzani, Pier Luigi

    2015-01-01

    The recent finding that MYC-driven cancers are sensitive to inhibition of the DNA damage response (DDR) pathway, prompted us to investigate the role of DDR pathway as therapeutic target in diffuse large B-cell lymphoma (DLBCL), which frequently overexpresses the MYC oncogene. In a preliminary immunohistochemical study conducted on 99 consecutive DLBCL patients, we found that about half of DLBCLs showed constitutive expression of the phosphorylated forms of checkpoint kinases (CHK) and CDC25c, markers of DDR activation, and of phosphorylated histone H2AX (γH2AX), marker of DNA damage and genomic instability. Constitutive γH2AX expression correlated with c-MYC levels and DDR activation, and defined a subset of tumors characterised by poor outcome. Next, we used the CHK inhibitor PF-0477736 as a tool to investigate whether the inhibition of the DDR pathway might represent a novel therapeutic approach in DLBCL. Submicromolar concentrations of PF-0477736 hindered proliferation in DLBCL cell lines with activated DDR pathway. These results were fully recapitulated with a different CHK inhibitor (AZD-7762). Inhibition of checkpoint kinases induced rapid DNA damage accumulation and apoptosis in DLBCL cell lines and primary cells. These data suggest that pharmacologic inhibition of DDR through targeting of CHK kinases may represent a novel therapeutic strategy in DLBCL. PMID:25544753

  17. Pineal Diffuse Large B-Cell Lymphoma Concomitant With Pituitary Prolactinoma: Possible Correlation Between 2 Distinguished Pathologies

    PubMed Central

    Kim, Yeong-Jin; Kim, Hee Kyung; Yang, Deok-Hwan; Jung, Shin; Noh, Myung-Giun; Lee, Jae-Hyuk; Lee, Kyung-Hwa; Moon, Kyung-Sub

    2016-01-01

    Abstract This is the first reported case of pineal lymphoma with concomitant prolactin-producing pituitary adenoma. A 51-year-old male experienced worsening headaches accompanied by nausea, diplopia, and memory loss for 1 month. Cranial nerve examination revealed bilateral upward gaze limitation with convergence impairment, which is known as Parinaud syndrome. Magnetic resonance images revealed a mass in the pineal gland with a coexisting mass within the enlarged sella fossa. Hormone analysis revealed hyperprolactinemia. The pineal mass was removed without injuring the hypothalamus, brain stem, or any neighboring vessels. Pathology examination confirmed the diagnosis of diffuse large B-cell lymphoma (DLBCL) involving the pineal gland. After further studies, the pineal lymphoma was determined to be a secondary tumor from a gastric primary tumor. The patient died 6 months after diagnosis due to systemic progression of DLBCL. Although the mechanistic link between hyperprolactinemia and lymphoma progression has not been clarified on a clinical basis, high prolactin levels may contribute to the rapid progression and therapeutic resistance of the lymphoma. PMID:26937937

  18. Differential regulation of mTOR signaling determines sensitivity to AKT inhibition in diffuse large B cell lymphoma.

    PubMed

    Ezell, Scott A; Wang, Suping; Bihani, Teeru; Lai, Zhongwu; Grosskurth, Shaun E; Tepsuporn, Suprawee; Davies, Barry R; Huszar, Dennis; Byth, Kate F

    2016-02-23

    Agents that target components of the PI3K/AKT/mTOR pathway are under investigation for the treatment of diffuse large B cell lymphoma (DLBCL). Given the highly heterogeneous nature of DLBCL, it is not clear whether all subtypes of DLBCL will be susceptible to PI3K pathway inhibition, or which kinase within this pathway is the most favorable target. Pharmacological profiling of a panel of DLBCL cell lines revealed a subset of DLBCL that was resistant to AKT inhibition. Strikingly, sensitivity to AKT inhibitors correlated with the ability of these inhibitors to block phosphorylation of S6K1 and ribosomal protein S6. Cell lines resistant to AKT inhibition activated S6K1 independent of AKT either through upregulation of PIM2 or through activation by B cell receptor (BCR) signaling components. Finally, combined inhibition of AKT and BTK, PIM2, or S6K1 proved to be an effective strategy to overcome resistance to AKT inhibition in DLBCL. PMID:26824321

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

    PubMed Central

    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

  20. Pineal Diffuse Large B-Cell Lymphoma Concomitant With Pituitary Prolactinoma: Possible Correlation Between 2 Distinguished Pathologies: A Case Report.

    PubMed

    Kim, Yeong-Jin; Kim, Hee Kyung; Yang, Deok-Hwan; Jung, Shin; Noh, Myung-Giun; Lee, Jae-Hyuk; Lee, Kyung-Hwa; Moon, Kyung-Sub

    2016-02-01

    This is the first reported case of pineal lymphoma with concomitant prolactin-producing pituitary adenoma.A 51-year-old male experienced worsening headaches accompanied by nausea, diplopia, and memory loss for 1 month. Cranial nerve examination revealed bilateral upward gaze limitation with convergence impairment, which is known as Parinaud syndrome. Magnetic resonance images revealed a mass in the pineal gland with a coexisting mass within the enlarged sella fossa. Hormone analysis revealed hyperprolactinemia. The pineal mass was removed without injuring the hypothalamus, brain stem, or any neighboring vessels. Pathology examination confirmed the diagnosis of diffuse large B-cell lymphoma (DLBCL) involving the pineal gland. After further studies, the pineal lymphoma was determined to be a secondary tumor from a gastric primary tumor. The patient died 6 months after diagnosis due to systemic progression of DLBCL.Although the mechanistic link between hyperprolactinemia and lymphoma progression has not been clarified on a clinical basis, high prolactin levels may contribute to the rapid progression and therapeutic resistance of the lymphoma. PMID:26937937

  1. Phantom for assessment of fat suppression in large field-of-view diffusion-weighted magnetic resonance imaging

    NASA Astrophysics Data System (ADS)

    Winfield, J. M.; Douglas, N. H. M.; deSouza, N. M.; Collins, D. J.

    2014-05-01

    We present the development and application of a phantom for assessment and optimization of fat suppression over a large field-of-view in diffusion-weighted magnetic resonance imaging at 1.5 T and 3 T. A Perspex cylinder (inner diameter 185 mm, height 300 mm) which contains a second cylinder (inner diameter 140 mm) was constructed. The inner cylinder was filled with water doped with copper sulphate and sodium chloride and the annulus was filled with corn oil, which closely matches the spectrum and longitudinal relaxation times of subcutaneous abdominal fat. Placement of the phantom on the couch at 45° to the z-axis presented an elliptical cross-section, which was of a similar size and shape to axial abdominal images. The use of a phantom for optimization of fat suppression allowed quantitative comparison between studies without the differences introduced by variability between human subjects. We have demonstrated that the phantom is suitable for selection of inversion delay times, spectral adiabatic inversion recovery delays and assessment of combinatorial methods of fat suppression. The phantom is valuable in protocol development and the assessment of new techniques, particularly in multi-centre trials.

  2. Current strategies in the diagnosis of diffuse large B-cell lymphoma of the central nervous system.

    PubMed

    Baraniskin, Alexander; Deckert, Martina; Schulte-Altedorneburg, Gernot; Schlegel, Uwe; Schroers, Roland

    2012-02-01

    Lymphomas can arise within the central nervous system (CNS) as primary CNS lymphoma (PCNSL) typically involving the brain and less often the leptomeninges, eyes, and spinal cord. In contrast to PCNSL, secondary CNS lymphoma (SCNSL) is considered to originate as quasi metastasis from systemic lymphoma spreading to the CNS. Both types of CNS lymphomas are predominantly tumours of the diffuse large B-cell type and represent aggressive diseases necessitating a rapid diagnosis. Following neuroimaging based on magnetic resonance imaging, stereotaxy and histopathological diagnosis of CNS lymphoma currently remain obligatory to plan treatment. However, progress in cytopathological, immunophenotypic, and molecular genetic analyses of the cerebrospinal fluid (CSF) has been achieved recently and potentially will facilitate lymphoma diagnosis in the future. This review describes the diagnostic procedures in patients with suspected CNS lymphomas, primarily PCNSL. In addition to a summary of the standard diagnostic work-up, an overview and discussion of current data on different techniques for evaluation of the CSF in CNS lymphoma are given. PMID:22077417

  3. Canine Lymphoma, More Than a Morphological Diagnosis: What We Have Learned about Diffuse Large B-Cell Lymphoma

    PubMed Central

    Aresu, Luca

    2016-01-01

    Diffuse large B-cell lymphoma (DLBCL) is the most common canine aggressive B-cell lymphoma worldwide, and new recent molecular approaches have shown that DLBCL constitutes a heterogeneous tumor that cannot be unraveled by morphology and immunophenotype. DLBCL behaves aggressively, typically progressing over a short period of time, and the therapy response may be difficult to be predicted. Recently, the rate of bone marrow infiltration by flow cytometry has been demonstrated to be prognostic, but more sensible markers are needed. As the clinical behavior is different, there is vast clinical and basic research devoted to identifying prognostically or biologically distinct DLBCL subgroups. Transcriptomic analysis by gene expression profile, copy number variations by array comparative genomic hybridization and epigenetic perturbations have tentatively described this heterogeneity. Molecular subgroups using oncogenic pathways and target genes have also been correlated to different outcome in a small number of cases. The objectives of this review are to summarize the current knowledge on the biology, clinical, and pathological characteristics of canine DLBCL. To date, DLBCL probably is the most investigated tumor in veterinary medicine, and its relevance as spontaneous model for human DLBCL has been confirmed by these studies. In future, these discoveries will ultimately lead to a better understanding of the underlying disease mechanisms, possibly translating into more effective therapeutic strategies.

  4. Hepatitis B virus reactivation after withdrawal of prophylactic antiviral therapy in patients with diffuse large B cell lymphoma.

    PubMed

    Liu, Wei Ping; Wang, Xiao Pei; Zheng, Wen; Ping, Ling Yan; Zhang, Chen; Wang, Gui Qiang; Song, Yu Qin; Zhu, Jun

    2016-06-01

    The exact incidence and severity of hepatitis B virus (HBV) reactivation after the withdrawal of prophylactic antiviral therapy (delayed HBV reactivation) is unknown. We retrospectively analyzed 107 newly diagnosed diffuse large B cell lymphoma patients with HBV infection who received chemotherapy. The median time from the cessation of antitumor therapy to the withdrawal of prophylactic antiviral therapy was 6.1 months. The incidence of delayed HBV reactivation was 21.7% in HBsAg-positive group and 0 in HBsAg-negative/anti-HBc-positive group (P < 0.001). No HBV-related fulminant hepatitis or hepatitis-related death occurred. The multivariate analysis showed that female gender and lengthy cycles of chemotherapy (>8 cycles) were independent risk factors of HBV reactivation in HBsAg-positive patients. In conclusion, prophylactic antiviral therapy could be withdrawn 6 months after the cessation of chemotherapy in HBsAg-negative/anti-HBc-positive patients. However, a longer course of prophylactic antiviral drug administration may be an optimal option to prevent delayed HBV reactivation for HBsAg-positive patients. PMID:26727044

  5. Galectin-3 binds to CD45 on diffuse large B-cell lymphoma cells to regulate susceptibility to cell death

    PubMed Central

    Clark, Mary C.; Pang, Mabel; Hsu, Daniel K.; Liu, Fu-Tong; de Vos, Sven; Gascoyne, Randy D.; Said, Jonathan

    2012-01-01

    Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma and an aggressive malignancy. Galectin-3 (gal-3), the only antiapoptotic member of the galectin family, is overexpressed in DLBCL. While gal-3 can localize to intracellular sites, gal-3 is secreted by DLBCL cells and binds back to the cell surface in a carbohydrate-dependent manner. The major counterreceptor for gal-3 on DLBCL cells was identified as the transmembrane tyrosine phosphatase CD45. Removal of cell-surface gal-3 from CD45 with the polyvalent glycan inhibitor GCS-100 rendered DLBCL cells susceptible to chemotherapeutic agents. Binding of gal-3 to CD45 modulated tyrosine phosphatase activity; removal of endogenous cell-surface gal-3 from CD45 with GCS-100 increased phosphatase activity, while addition of exogenous gal-3 reduced phosphatase activity. Moreover, the increased susceptibility of DLBCL cells to chemotherapeutic agents after removal of gal-3 by GCS-100 required CD45 phosphatase activity. Gal-3 binding to a subset of highly glycosylated CD45 glycoforms was regulated by the C2GnT-1 glycosyltransferase, indicating that specific glycosylation of CD45 is important for regulation of gal-3–mediated signaling. These data identify a novel role for cell-surface gal-3 and CD45 in DLBCL survival and suggest novel therapeutic targets to sensitize DLBCL cells to death. PMID:23065155

  6. Exome sequencing reveals novel mutation targets in diffuse large B-cell lymphomas derived from Chinese patients

    PubMed Central

    de Miranda, Noel F. C. C.; Georgiou, Konstantinos; Chen, Longyun; Wu, Chenglin; Gao, Zhibo; Zaravinos, Apostolos; Lisboa, Susana; Enblad, Gunilla; Teixeira, Manuel R.; Zeng, Yixin

    2014-01-01

    Next-generation sequencing studies on diffuse large B-cell lymphomas (DLBCLs) have revealed novel targets of genetic aberrations but also high intercohort heterogeneity. Previous studies have suggested that the prevalence of disease subgroups and cytogenetic profiles differ between Western and Asian patients. To characterize the coding genome of Chinese DLBCL, we performed whole-exome sequencing of DNA derived from 31 tumors and respective peripheral blood samples. The mutation prevalence of B2M, CD70, DTX1, LYN, TMSB4X, and UBE2A was investigated in an additional 105 tumor samples. We discovered 11 novel targets of recurrent mutations in DLBCL that included functionally relevant genes such as LYN and TMSB4X. Additional genes were found mutated at high frequency (≥10%) in the Chinese cohort including DTX1, which was the most prevalent mutation target in the Notch pathway. We furthermore demonstrated that mutations in DTX1 impair its function as a negative regulator of Notch. Novel and previous unappreciated targets of somatic mutations in DLBCL identified in this study support the existence of additional/alternative tumorigenic pathways in these tumors. The observed differences with previous reports might be explained by the genetic heterogeneity of DLBCL, the germline genetic makeup of Chinese individuals, and/or exposure to distinct etiological agents. PMID:25171927

  7. Colonic diffuse large B-cell lymphoma in a liver transplant patient with historically very low tacrolimus levels.

    PubMed

    Moore, Christopher M; Lamzabi, Ihab; Bartels, Anne K; Jakate, Shriram; Van Thiel, David H

    2012-01-01

    Posttransplant lymphoproliferative disorders (PTLDs) comprise a wide spectrum of hematologic malignancies that are found increasingly in orthotopic liver transplant (OLT) patients given the rising frequency of these surgeries and their long-term success. PTLDs are highly correlated with both the Epstein-Barr virus (EBV) infection and the degree of immunosuppression involved. Herein is reported a case of a 53-year-old male with successfully treated hepatitis C virus genotype 4 and hepatocellular carcinoma who underwent OLT and developed symptoms of weakness and poor appetite 4 years later while on tacrolimus 3 mg b.i.d. with historically very low plasma levels. He was found to be anemic and colonoscopy revealed a 4.5 cm cecal diffuse large B-cell lymphoma (DLBCL). Further workup revealed mesenteric lymph node enlargement consistent and nodal DLBCL dissemination. He was treated with cyclophosphamide-hydroxyldaunorubicin-oncovin-prednisone-rituximab (CHOP-R) chemotherapy and his tacrolimus dose was lowered. Additionally, he manifested PTLD-associated cryoglobulinemia leading to acute kidney injury. After a prolonged hospitalization he was discharged with close followup. PMID:23259146

  8. Salvage chemotherapy and autologous stem cell transplant in primary refractory diffuse large B-cell lymphoma: outcomes and prognostic factors.

    PubMed

    Telio, David; Fernandes, Kim; Ma, Clement; Tsang, Richard; Keating, Armand; Crump, Michael; Kuruvilla, John

    2012-05-01

    Patients with primary refractory diffuse large B-cell lymphoma (REF DLBCL: progression on or within 3 months of completion of primary therapy) sensitive to salvage chemotherapy undergo autologous stem cell transplant (ASCT). We conducted a retrospective review of 111 patients with REF DLBCL treated between 1999 and 2007. Primary treatment consisted of cyclophosphamide, adriamycin, vincristine and prednisone (CHOP; 66%) and rituximab with CHOP (R-CHOP; 33%); 14% received involved field radiation. The response rate (RR) to first salvage chemotherapy was 23% (RR by regimen: dexamethasone, cytosine arabinoside and cisplatin [DHAP] 15%, etoposide, Solu-Medrol, cytosine arabinoside and cisplatin [ESHAP] 36%, and gemcitabine, dexamethasone and cisplatin [GDP] 45%); 25% (n = 28) of patients underwent ASCT. With a median follow-up of 5.9 months (range 1-94), the median progression-free and overall survival from primary treatment failure was 3 and 10 months, respectively. Outcomes in patients with REF DLBCL after CHOP or R-CHOP appear equally poor. Second-generation platinum-containing regimens (ESHAP, GDP) may be superior to DHAP in this setting. Novel, prospectively evaluated treatment approaches should be pursued in REF DLBCL. PMID:22136378

  9. Epstein-Barr virus positive diffuse large B-cell lymphoma predict poor outcome, regardless of the age.

    PubMed

    Lu, Ting-Xun; Liang, Jin-Hua; Miao, Yi; Fan, Lei; Wang, Li; Qu, Xiao-Yan; Cao, Lei; Gong, Qi-Xing; Wang, Zhen; Zhang, Zhi-Hong; Xu, Wei; Li, Jian-Yong

    2015-01-01

    Epstein-Barr virus (EBV) positive diffuse large B-cell lymphoma (DLBCL) of the elderly is defined as patients older than 50 years alone. However, recent studies showed young patients with sound immune status could also be affected. In this study, we investigated the clinical features and outcomes of patients with EBV positive DLBCL in the different age groups using different EBER cut-off values. The prevalence of EBV positive DLBCL was 14.0% (35/250) and 10.4% (26/250) for EBER cut-off of 20% and 50%, respectively. With both EBER cut-off values, patients with EBV DLBCL shared many unfavorable prognostic characteristics, regardless of age. EBV positive patients, both in the elderly and young groups, showed significantly worse overall survival and progression-free survival than negative cases. Moreover, no significant differences of outcomes were identified between different age groups with EBV positive DLBCL. In conclusion, EBV positive DLBCL patients, regardless of age, shared similar poor prognostic features and showed worse outcome than negative cases. We suggest that the age criterion of EBV positive DLBCL of the elderly, and possibly the name itself, be modified in future. PMID:26202875

  10. Two-Dimensional Matrix Algorithm Using Detrended Fluctuation Analysis to Distinguish Burkitt and Diffuse Large B-Cell Lymphoma

    PubMed Central

    Yeh, Rong-Guan; Lin, Chung-Wu; Abbod, Maysam F.; Shieh, Jiann-Shing

    2012-01-01

    A detrended fluctuation analysis (DFA) method is applied to image analysis. The 2-dimensional (2D) DFA algorithms is proposed for recharacterizing images of lymph sections. Due to Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL), there is a significant different 5-year survival rates after multiagent chemotherapy. Therefore, distinguishing the difference between BL and DLBCL is very important. In this study, eighteen BL images were classified as group A, which have one to five cytogenetic changes. Ten BL images were classified as group B, which have more than five cytogenetic changes. Both groups A and B BLs are aggressive lymphomas, which grow very fast and require more intensive chemotherapy. Finally, ten DLBCL images were classified as group C. The short-term correlation exponent α1 values of DFA of groups A, B, and C were 0.370 ± 0.033, 0.382 ± 0.022, and 0.435 ± 0.053, respectively. It was found that α1 value of BL image was significantly lower (P < 0.05) than DLBCL. However, there is no difference between the groups A and B BLs. Hence, it can be concluded that α1 value based on DFA statistics concept can clearly distinguish BL and DLBCL image. PMID:23365623

  11. Epratuzumab with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy in patients with previously untreated diffuse large B-cell lymphoma

    PubMed Central

    Micallef, Ivana N. M.; Maurer, Matthew J.; Wiseman, Gregory A.; Nikcevich, Daniel A.; Kurtin, Paul J.; Cannon, Michael W.; Perez, Domingo G.; Soori, Gamini S.; Link, Brian K.; Habermann, Thomas M.

    2011-01-01

    Approximately 60% of patients with diffuse large B-cell non-Hodgkin lymphoma (DLBCL) are curable with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemoimmunotherapy. Epratuzumab (E) is an unlabeled anti-CD22 monoclonal antibody with efficacy in relapsed DLBCL. This phase 2 trial tested the safety and efficacy of combining E with R-CHOP (ER-CHOP) in untreated DLBCL. A secondary aim was to assess the efficacy of interim positron emission tomography (PET) to predict outcome in DLBCL. Standard R-CHOP with the addition of E 360 mg/m2 intravenously was administered for 6 cycles. A total of 107 patients were enrolled in the study. Toxicity was similar to standard R-CHOP. Overall response rate in the 81 eligible patients was 96% (74% CR/CRu) by computed tomography scan and 88% by PET. By intention to treat analysis, at a median follow-up of 43 months, the event-free survival (EFS) and overall survival (OS) at 3 years in all 107 patients were 70% and 80%, respectively. Interim PET was not associated with EFS or OS. Comparison with a cohort of 215 patients who were treated with R-CHOP showed an improved EFS in the ER-CHOP patients. ER-CHOP is well tolerated and results appear promising as a combination therapy. This study was registered at www.clinicaltrials.gov as #NCT00301821. PMID:21673350

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

    PubMed

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

    2012-01-15

    Plitidepsin (Aplidin), an antitumor agent of marine origin, presently is undergoing phase II/III clinical trials, and has shown promise for the treatment of lymphoma. Here, we describe the antitumor effects of plitidepsin alone and in combination with rituximab and investigated the effects of each drug and the combination on the cell cycle and mechanism of cell death. Several Diffuse Large Cell Lymphoma (DLCL) lines and Burkitt cell lines were tested for sensitivity to plitidepsin and rituximab. All DLCL and Burkitt lymphoma cell lines were inhibited by plitidepsin in nanomolar concentrations, while rituximab sensitivity varied among different cell lines. Ramos and the RL cell lines proved sensitive to rituximab and were used to test the effects of each of the two drugs. The two agents exhibited synergism at all tested concentrations. For in vivo studies, irradiated athymic nude mice were engrafted with the Ramos lymphoma. Treatment was initiated when the tumors were ~0.5 cm in diameter, and toxic and therapeutic effects were monitored. In the in vivo study, additive effects of the combined two drugs, was demonstrated without an increase in host toxicity. The in vitro synergy and the in vivo additive antitumor effects without an increase in host toxicity with two relatively non-marrow suppressive agents encourages further development of this combination for treatment of aggressive B-cell lymphomas. PMID:22336911

  13. Primary Diffuse Large B-Cell Lymphoma of Central Nervous System: Is Still Surgery an Unorthodox Treatment?

    PubMed

    Siasios, Ioannis; Fotiadou, Aggeliki; Fotakopoulos, George; Ioannou, Maria; Anagnostopoulos, Vassilios; Fountas, Konstantinos

    2015-12-01

    Primary central nervous system lymphoma (PCNSL) is characterized as an extra-nodal non-Hodgkin lymphoma which develops from the neuraxis. The purpose was to report a case of a patient with a supra-tentorial tumor who underwent subtotal resection of his tumor as his biopsy was not indicative of a PCNSL tumor and had uneventful recovery until his last follow-up. A 42-year-old man was admitted to our department for generalized epileptic seizures. CT and MRI examinations revealed a tumor in his right parietal-occipital lobe that was surrounded by edema and was enhancing after gadolinium administration. The patient underwent a navigation-assisted parieto-occipital craniotomy and posterior parietal transcortical approach for tumor biopsy which was not indicative of PCNSL tumor. The surgical team decided to remove the tumor on site. Histological analysis of the resected specimen showed primary diffuse large B-cell lymphoma. Combined chemotherapy and radiation therapy was applied to the patient, and at his last follow-up (16 months), he is tumor free. In our case as in several other studies during the last decade, the outcome after the surgical resection of a PCNSL tumor in combination to radiation and chemotherapy was unexpectedly good. The role of surgery probably should be reconsidered for single lesion PCNSL tumors. PMID:26566417

  14. A role for eukaryotic initiation factor 4B overexpression in the pathogenesis of diffuse large B-cell lymphoma

    PubMed Central

    Horvilleur, E; Sbarrato, T; Hill, K; Spriggs, R V; Screen, M; Goodrem, P J; Sawicka, K; Chaplin, L C; Touriol, C; Packham, G; Potter, K N; Dirnhofer, S; Tzankov, A; Dyer, M J S; Bushell, M; MacFarlane, M; Willis, A E

    2014-01-01

    Dysregulated expression of factors that control protein synthesis is associated with poor prognosis of many cancers, but the underlying mechanisms are not well defined. Analysis of the diffuse large B-cell lymphoma (DLBCL) translatome revealed selective upregulation of mRNAs encoding anti-apoptotic and DNA repair proteins. We show that enhanced synthesis of these proteins in DLBCL is mediated by the relief of repression that is normally imposed by structure in the 5′-untranslated regions of their corresponding mRNAs. This process is driven by signaling through mammalian target of rapamycin, resulting in increased synthesis of eukaryotic initiation factor (eIF) 4B complex (eIF4B), a known activator of the RNA helicase eIF4A. Reducing eIF4B expression alone is sufficient to decrease synthesis of proteins associated with enhanced tumor cell survival, namely DAXX, BCL2 and ERCC5. Importantly, eIF4B-driven expression of these key survival proteins is directly correlated with patient outcome, and eIF4B, DAXX and ERCC5 are identified as novel prognostic markers for poor survival in DLBCL. Our work provides new insights into the mechanisms by which the cancer-promoting translational machinery drives lymphomagenesis. PMID:24135829

  15. ATM deficiency promotes development of murine B-cell lymphomas that resemble diffuse large B-cell lymphoma in humans

    PubMed Central

    Hathcock, Karen S.; Padilla-Nash, Hesed M.; Camps, Jordi; Shin, Dong-Mi; Triner, Daniel; Shaffer, Arthur L.; Maul, Robert W.; Steinberg, Seth M.; Gearhart, Patricia J.; Staudt, Louis M.; Morse, Herbert C.; Ried, Thomas

    2015-01-01

    The serine-threonine kinase ataxia-telangiectasia mutated (ATM) plays a central role in maintaining genomic integrity. In mice, ATM deficiency is exclusively associated with T-cell lymphoma development, whereas B-cell tumors predominate in human ataxia-telangiectasia patients. We demonstrate in this study that when T cells are removed as targets for lymphomagenesis and as mediators of immune surveillance, ATM-deficient mice exclusively develop early-onset immunoglobulin M+ B-cell lymphomas that do not transplant to immunocompetent mice and that histologically and genetically resemble the activated B cell–like (ABC) subset of human diffuse large B-cell lymphoma (DLBCL). These B-cell lymphomas show considerable chromosomal instability and a recurrent genomic amplification of a 4.48-Mb region on chromosome 18 that contains Malt1 and is orthologous to a region similarly amplified in human ABC DLBCL. Of importance, amplification of Malt1 in these lymphomas correlates with their dependence on nuclear factor (NF)-κB, MALT1, and B-cell receptor (BCR) signaling for survival, paralleling human ABC DLBCL. Further, like some human ABC DLBCLs, these mouse B-cell lymphomas also exhibit constitutive BCR-dependent NF-κB activation. This study reveals that ATM protects against development of B-cell lymphomas that model human ABC DLBCL and identifies a potential role for T cells in preventing the emergence of these tumors. PMID:26400962

  16. Simultaneous Bilateral Nonarteritic Anterior Ischemic Optic Neuropathy in a Patient with a History of Diffuse Large B-Cell Lymphoma

    PubMed Central

    Lazar, David B.; Lemor, Daniel; Brown, Archie; Nussdorf, Jonathan D.

    2015-01-01

    Background Nonarteritic anterior ischemic optic neuropathy (NAAION) has a poorly understood etiology, and the onset of simultaneous bilateral NAAION in a patient <50 years without identifiable systemic risk factors is rare. Case Report We present the case of a patient with acute painless monocular vision loss and bilateral optic disc edema who subsequently developed painless vision loss in the fellow eye. The patient's history was significant for diffuse large B-cell lymphoma, and our pressing diagnostic concern was to determine if his vision loss and bilateral optic disc changes represented lymphomatous infiltrates. A complete ocular exam demonstrated findings consistent with simultaneous bilateral NAAION. After an extensive systemic workup for malignancy with central nervous system involvement, vasculitis, and other entities associated with NAAION, we determined that the patient's primary risk factor for developing bilateral ischemic optic neuropathies was his crowded optic discs. Conclusion This case supports the hypothesis that a crowded optic disc is a sufficient primary risk factor for developing NAAION. PMID:25829891

  17. Constitutive NF-κB Activation Underlines Major Mechanism of Drug Resistance in Relapsed Refractory Diffuse Large B Cell Lymphoma

    PubMed Central

    2015-01-01

    Diffuse large B cell lymphoma (DLBCL) is the most common subtype of B cell non-Hodgkin's lymphoma (NHL), encompassing 30–40% of the estimated 70,000 cases of NHL in 2014 in the USA. Despite major improvements with immune-chemotherapy, the fraction of patients who still succumb to a refractory or relapsed disease remains high. This review addresses whether the better understanding of the biology of DLBCL defines new therapeutic avenues that may overcome the emerging resistance of this disease to traditional immune-chemotherapy, such as rituximab in combination with traditional chemotherapy agents. Emerging targeted therapy for relapsed refractory DLBCL encompasses more complex molecular abnormalities involving signaling pathways other than NF-κB as mechanism of resistance to immune-chemotherapy. Our review suggests that NF-κB pathway is an important crossroad where other pathways converge as phenotype of resistance that emerges in patients who fail frontline and salvage immune-chemotherapy. Future efforts should aim at targeting the role of NF-κB resistance in clinical trials, where novel agents like lenalidomide and proteasome inhibitors with established activity in this perspective will be an important component in combination therapy, along with new monoclonal antibody, BTK-inhibitors, and other novel therapy agents. PMID:25984532

  18. The copper chelator ATN-224 induces caspase-independent cell death in diffuse large B cell lymphoma

    PubMed Central

    LEE, KRISTY; HART, MATTHEW R.; BRIEHL, MARGARET M.; MAZAR, ANDREW P.; TOME, MARGARET E.

    2014-01-01

    Bcl-2 and other anti-apoptotic proteins are associated with defective caspase-dependent apoptotic pathways, resulting in chemoresistance. We have previously shown that ATN-224, a copper chelator drug, induces cell death in murine thymic lymphoma cells transfected with Bcl-2. In the current study, we tested whether ATN-224 was effective in diffuse large B cell lymphoma (DLBCL) cells, which have increased anti-apoptotic proteins through translocation or amplification. We found that nanomolar concentrations of ATN-224 induced cell death in DLBCL cells independent of Bcl-2, Bcl-xL or Mcl-1 status. ATN-224 treatment resulted in mitochondrial dysfunction, release of apoptosis-inducing factor (AIF) and induction of caspase-independent cell death. In addition, ATN-224 degraded Mcl-1 and enhanced the effect of the BH3 mimetic ABT-263. These findings indicate that ATN-224 has potential as a therapeutic for the treatment of DLBCL. Induction of caspase-independent cell death in apoptosis-resistant DLBCL would provide a therapeutic alternative for the treatment of refractory disease. PMID:24788952

  19. Maintenance therapy with interferon-alpha 2b, cyclophosphamide, and prednisone in aggressive diffuse large cell lymphoma.

    PubMed

    Avilés, Agustin; Neri, Natividad; Nambo, M Jesús; Castañeda, Claudia; Talavera, Alejandra; Huerta-Guzmán, Judith; Murillo, Edgar

    2004-04-01

    Maintenance therapy in patients with aggressive malignant lymphoma using biological modifiers remains uncertain. We conducted a controlled clinical trial to evaluate the efficacy and toxicity of interferon-alpha 2b, cyclophosphamide, and prednisone as maintenance therapy in patients with aggressive diffuse large B cell lymphomas in complete remission after aggressive chemotherapy. In an intent-to-treat analysis, 169 patients were eligible for this study; the end points were event-free survival (EFS) and overall survival (OS). With a median follow-up of 49.3 months, no statistical differences were observed and actuarial curves at 5 years showed that EFS was 71% (95% confidence interval [CI], 63-79%) for patients who received maintenance compared to 63% (95% CI, 59-71%) for patients in control group (p = 0.05). No statistical differences were observed in OS between maintenance arm: 84% (95% CI, 78-89%) and control group 83% (95% CI, 77-88%) in control group (p = 0.2). All patients received the maintenance therapy as planned and in time, thus dose intensity was considered 1.0 in all cases. Acute toxicity was mild, and no delay or suspension of treatment was necessary. Late toxicity was not evident until now. We conclude that use of maintenance therapy combining interferon-alpha 2b, cyclophosphamide, and prednisone is not useful in patients with aggressive lymphoma if they had been treated with aggressive combined chemotherapy. PMID:15186737

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

    PubMed Central

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

    2015-01-01

    In searching for small-molecule compounds that inhibit proliferation and survival of diffuse large B-cell lymphoma (DLBCL) cells and may, therefore, be exploited as potential therapeutic agents for this disease, we identified the commonly used and well-tolerated antibiotic doxycycline as a strong candidate. Here, we demonstrate that doxycycline inhibits the growth of DLBCL cells both in vitro and in mouse xenograft models. In addition, we show that doxycycline accumulates in DLBCL cells to high concentrations and affects multiple signaling pathways that are crucial for lymphomagenesis. Our data reveal the deneddylating activity of COP-9 signalosome (CSN) as a novel target of doxycycline and suggest that doxycycline may exert its effects in DLBCL cells in part through a CSN5-HSP90 pathway. Consistently, knockdown of CSN5 exhibited similar effects as doxycycline treatment on DLBCL cell survival and HSP90 chaperone function. In addition to DLBCL cells, doxycycline inhibited growth of several other types of non-Hodgkin lymphoma cells in vitro. Together, our results suggest that doxycycline may represent a promising therapeutic agent for DLBCL and other non-Hodgkin lymphomas subtypes. PMID:26142707

  1. DUSP4 deficiency caused by promoter hypermethylation drives JNK signaling and tumor cell survival in diffuse large B cell lymphoma

    PubMed Central

    Schmid, Corina A.; Robinson, Mark D.; Scheifinger, Nicole A.; Müller, Sebastian; Cogliatti, Sergio; Tzankov, Alexandar

    2015-01-01

    The epigenetic dysregulation of tumor suppressor genes is an important driver of human carcinogenesis. We have combined genome-wide DNA methylation analyses and gene expression profiling after pharmacological DNA demethylation with functional screening to identify novel tumor suppressors in diffuse large B cell lymphoma (DLBCL). We find that a CpG island in the promoter of the dual-specificity phosphatase DUSP4 is aberrantly methylated in nodal and extranodal DLBCL, irrespective of ABC or GCB subtype, resulting in loss of DUSP4 expression in 75% of >200 examined cases. The DUSP4 genomic locus is further deleted in up to 13% of aggressive B cell lymphomas, and the lack of DUSP4 is a negative prognostic factor in three independent cohorts of DLBCL patients. Ectopic expression of wild-type DUSP4, but not of a phosphatase-deficient mutant, dephosphorylates c-JUN N-terminal kinase (JNK) and induces apoptosis in DLBCL cells. Pharmacological or dominant-negative JNK inhibition restricts DLBCL survival in vitro and in vivo and synergizes strongly with the Bruton’s tyrosine kinase inhibitor ibrutinib. Our results indicate that DLBCL cells depend on JNK signaling for survival. This finding provides a mechanistic basis for the clinical development of JNK inhibitors in DLBCL, ideally in synthetic lethal combinations with inhibitors of chronic active B cell receptor signaling. PMID:25847947

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

    PubMed

    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

  3. Diffuse X-ray emission from the superbubbles N70 and N185 in the Large Magellanic Cloud

    SciTech Connect

    Reyes-Iturbide, J.; Rodríguez-González, A.; Velázquez, P. F.; Rosado, M.; Sánchez-Cruces, M.; Ambrocio-Cruz, P.

    2014-11-01

    We present a study of the diffuse X-ray emission from superbubbles (SBs) N70 (DEM L301) and N185 (DEM L25) located in the Large Magellanic Cloud, based on data from the XMM-Newton Satellite. We obtained spectra and images of these objects in the soft X-ray energy band. These X-ray spectra were fitted by a thermal plasma model, with temperatures of 2.6×10{sup 6} K and 2.3×10{sup 6} K, for N70 and N185, respectively. For N70, images show that X-ray emission comes from the inner regions of the SB when we compare the distribution of the X-ray and the optical emission, while for N185, the X-ray emission is partially confined by the optical shell. We suggest that the observed X-ray emission is caused by shock-heated gas, inside of the optical shells. We also obtained X-ray luminosities which exceed the values predicted by the standard analytical model. This fact shows that, in addition to the winds of the interior stars, it is necessary to consider another ingredient in the description, such as a supernova explosion, as has been proposed in previous numerical models.

  4. Case report of acute-on-chronic liver failure secondary to diffuse large B-cell lymphoma

    PubMed Central

    Siba, Yahuza; Obiokoye, Kenechukwu; Ferstenberg, Richard; Robilotti, James; Culpepper-Morgan, Joan

    2014-01-01

    Acute liver failure is a rare presentation of hematologic malignancy. Acute on chronic liver failure (ACLF) is a newly recognized clinical entity that describes acute hepatic decompensation in persons with preexisting liver disease. Diffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin’s lymphoma (NHL) with increasing incidence in older males, females and blacks. However, it has not yet been reported, to present with acute liver failure in patients with preexisting chronic liver disease due to human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infection. We describe a case of ACLF as the presenting manifestation of DLBCL in an elderly black man with HIV/HCV co-infection and prior Hodgkin’s disease in remission for three years. The rapidly fatal outcome of this disease is highlighted as is the distinction of ACLF from decompensated cirrhosis. Due to the increased prevalence of HIV/HCV co-infection in the African American 1945 to 1965 birth cohort and the fact that both are risk factors for chronic liver disease and NHL we postulate that the incidence of NHL presenting as ACLF may increase. PMID:25469050

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

    PubMed Central

    Kristensen, Lasse Sommer; Treppendahl, Marianne Bach; Asmar, Fazila; Girkov, Mia Seremet; Nielsen, Helene Myrtue; Kjeldsen, Tina Ellegaard; Ralfkiaer, Elisabeth; Hansen, Lise Lotte; Grønbæk, Kirsten

    2013-01-01

    The tumor suppressor genes MGMT and DAPK1 become methylated in several cancers including diffuse large B-cell lymphoma (DLBCL). However, allelic methylation patterns have not been investigated in DLBCL. We developed a fast and cost-efficient method for the analysis of allelic methylation based on pyrosequencing of methylation specific PCR (MSP) products including a SNP. Allelic methylation patterns were reliably analyzed in standards of known allelic methylation status even when diluted in unmethylated DNA to below 1% methylation. When studying 148 DLBCL patients MGMT and DAPK1 methylation was observed in 19% and 89%, respectively, and among methylated and heterozygous patients 29% and 55%, respectively, were biallelically methylated. An association between the T-allele of the rs16906252 SNP and MGMT methylation was observed (p-value = 0.04), and DAPK1 methylation of the A-allele was associated with shorter overall survival (p-value = 0.006). In future cancer research allelic MSP-pyrosequencing may be used to study a wide range of other loci. PMID:24071855

  6. Serum nuclear magnetic resonance-based metabolomics and outcome in diffuse large B-cell lymphoma patients - a pilot study.

    PubMed

    Stenson, Martin; Pedersen, Anders; Hasselblom, Sverker; Nilsson-Ehle, Herman; Karlsson, Bengt Göran; Pinto, Rui; Andersson, Per-Ola

    2016-08-01

    The prognosis for diffuse large B-cell lymphoma (DLBCL) patients with early relapse or refractory disease is dismal. To determine if clinical outcome correlated to diverse serum metabolomic profiles, we used (1)H nuclear magnetic resonance (NMR) spectroscopy and compared two groups of DLBCL patients treated with immunochemotherapy: i) refractory/early relapse (REF/REL; n=27) and ii) long-term progression-free (CURED; n = 60). A supervised multivariate analysis showed a separation between the groups. Among discriminating metabolites higher in the REF/REL group were the amino acids lysine and arginine, the degradation product cadaverine and a compound in oxidative stress (2-hydroxybutyrate). In contrast, the amino acids aspartate, valine and ornithine, and a metabolite in the glutathione cycle, pyroglutamate, were higher in CURED patients. Together, our data indicate that NMR-based serum metabolomics can identify a signature for DLBCL patients with high-risk of failing immunochemotherapy, prompting for larger validating studies which could lead to more individualized treatment of this disease. PMID:26887805

  7. Evaluation of the diffuse contamination of soils caused by residues coming from the large scale production of phosphate fertilisers

    NASA Astrophysics Data System (ADS)

    Martinez, M. J.; Perez-Sirvent, C.; Martinez-Lopez, S.; Bolivar, J. P.; Mosqueda, F.; Vaca, F.; Garcia-Tenorio, R.

    2012-04-01

    The obtaining of phosphate fertilizers results in large amounts of residues that are frequently accumulated in deposits or pools occupying a wide area. These residues are acidic, and contain variable amounts of trace elements and radionuclides. The potentially polluting agents can be leached by rainwater, and so transferred to the surface waters and then to the groundwater after soil infiltration. Since the distribution and thickness of the residue deposits are variable, the contaminants cannot be easily traced back to a single, well defined source, and so a diffuse contamination (nonpoint source pollution) of the surrounding soils and waters occurs. This communication reports the results obtained in the study of soils close to the phosphogypsum deposits placed near Rio Tinto (Huelva, Spain). The zone is affected not only by the mentioned residues but also by the tides due to the vicinity of the sea. The samples studied had a low organic content and a low acidity with average values of 30 mS/cm for the EC. The mineralogical study allowed illite, goethite, quartz, gypsum and kaolinite to be identified as the main mineralogical components. Although the arsenic level was relatively high (about 600 mg/Kg) the data proved that this element is not mobilized into water. Analytical data for 238U , 234U, 235U, 228Th, 230Th, 232Th, 226Ra, 228Ra, 210Po, 40K , 137Cs were also obtained.

  8. Constitutive activation of the DNA damage response pathway as a novel therapeutic target in diffuse large B-cell lymphoma.

    PubMed

    Derenzini, Enrico; Agostinelli, Claudio; Imbrogno, Enrica; Iacobucci, Ilaria; Casadei, Beatrice; Brighenti, Elisa; Righi, Simona; Fuligni, Fabio; Ghelli Luserna Di Rorà, Andrea; Ferrari, Anna; Martinelli, Giovanni; Pileri, Stefano; Zinzani, Pier Luigi

    2015-03-30

    The recent finding that MYC-driven cancers are sensitive to inhibition of the DNA damage response (DDR) pathway, prompted us to investigate the role of DDR pathway as therapeutic target in diffuse large B-cell lymphoma (DLBCL), which frequently overexpresses the MYC oncogene. In a preliminary immunohistochemical study conducted on 99 consecutive DLBCL patients, we found that about half of DLBCLs showed constitutive expression of the phosphorylated forms of checkpoint kinases (CHK) and CDC25c, markers of DDR activation, and of phosphorylated histone H2AX (γH2AX), marker of DNA damage and genomic instability. Constitutive γH2AX expression correlated with c-MYC levels and DDR activation, and defined a subset of tumors characterised by poor outcome. Next, we used the CHK inhibitor PF-0477736 as a tool to investigate whether the inhibition of the DDR pathway might represent a novel therapeutic approach in DLBCL. Submicromolar concentrations of PF-0477736 hindered proliferation in DLBCL cell lines with activated DDR pathway. These results were fully recapitulated with a different CHK inhibitor (AZD-7762). Inhibition of checkpoint kinases induced rapid DNA damage accumulation and apoptosis in DLBCL cell lines and primary cells. These data suggest that pharmacologic inhibition of DDR through targeting of CHK kinases may represent a novel therapeutic strategy in DLBCL. PMID:25544753

  9. Orbital MALT lymphoma, abdominal hodgkin lymphoma, and systemic diffuse large B-cell lymphoma develop sequentially in one patient.

    PubMed

    Matsuo, Toshihiko; Ichimura, Kouichi; Shinagawa, Katsuji

    2012-01-01

    In February 2002, a 42-year-old woman developed ocular adnexal extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT), MALT lymphoma, in the bilateral orbits involving lacrimal glands. She underwent 30 Gy external beam irradiation to the orbital lesions on both sides. She was well until November 2008 when she developed abdominal lymphadenopathy and transabdominal excisional biopsy showed mixed cellularity classical Hodgkin lymphoma at stage II. She underwent standard combination chemotherapy. In July 2010, she developed systemic lymphadenopathy and was diagnosed with diffuse large B-cell lymphoma (DLBCL) by cervical lymph node biopsy. She underwent rituximab monotherapy and finally allogeneic hematopoietic stem cell transplantation in October 2010, but died of renal failure in February 2011. Amplification by polymerase chain reaction of the immunoglobulin heavy chain gene gave rise to dominant discrete fragments of the same size between the orbital lesion with MALT lymphoma in 2002 and the cervical lymph node lesion with DLBCL in 2010. The sequential development of MALT lymphoma, Hodgkin lymphoma, and DLBCL in the long-term course of this patient suggests the common origin of the neoplastic cells, changing their pathological faces in response to irradiation and combination chemotherapy. PMID:22706530

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

    NASA Astrophysics Data System (ADS)

    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.

  11. Diffuse X-Ray Emission from the Superbubbles N70 and N185 in the Large Magellanic Cloud

    NASA Astrophysics Data System (ADS)

    Reyes-Iturbide, J.; Rosado, M.; Rodríguez-González, A.; Velázquez, P. F.; Sánchez-Cruces, M.; Ambrocio-Cruz, P.

    2014-11-01

    We present a study of the diffuse X-ray emission from superbubbles (SBs) N70 (DEM L301) and N185 (DEM L25) located in the Large Magellanic Cloud, based on data from the XMM-Newton Satellite. We obtained spectra and images of these objects in the soft X-ray energy band. These X-ray spectra were fitted by a thermal plasma model, with temperatures of 2.6× {{10}6} K and 2.3× {{10}6} K, for N70 and N185, respectively. For N70, images show that X-ray emission comes from the inner regions of the SB when we compare the distribution of the X-ray and the optical emission, while for N185, the X-ray emission is partially confined by the optical shell. We suggest that the observed X-ray emission is caused by shock-heated gas, inside of the optical shells. We also obtained X-ray luminosities which exceed the values predicted by the standard analytical model. This fact shows that, in addition to the winds of the interior stars, it is necessary to consider another ingredient in the description, such as a supernova explosion, as has been proposed in previous numerical models.

  12. Age cutoff for Epstein-Barr virus-positive diffuse large B-cell lymphoma–is it necessary?

    PubMed Central

    Ok, Chi Young; Ye, Qing; Li, Ling; Manyam, Ganiraju C.; Deng, Lijuan; Goswami, Rashmi R.; Wang, Xiaoxiao; Montes-Moreno, Santiago; Visco, Carlo; Tzankov, Alexandar; Dybkaer, Karen; Zhang, Li; Abramson, Jeremy; Sohani, Aliyah R.; Chiu, April; Orazi, Attilio; Zu, Youli; Bhagat, Govind; Richards, Kristy L.; Hsi, Eric D.; Choi, William W.L.; van Krieken, J. Han; Huh, Jooryung; Ponzoni, Maurilio; Ferreri, Andrés J.M.; Zhang, Shanxiang; Parsons, Ben M.; Xu, Mina; Møller, Michael B.; Winter, Jane N.; Piris, Miguel A.; Xu-Monette, Zijun Y.; Medeiros, L. Jeffrey; Young, Ken H.

    2015-01-01

    Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly (EBV+ DLBCL-e) is a molecularly distinct variant of DLBCL, characterized by a monoclonal B-cell proliferation that occurs in patients >50 years of age without a history or clinicopathologic evidence of immunodeficiency. However, patients with EBV+ DLBCL younger than 50-years-old also exist in Western countries. We evaluated the clinicopathologic, immunophenotypic and genetic features in Cacausian patients with EBV+ DLBCL who are ≤50 years of age and compared this patient group to patients who are >50 years. In patients who are ≤50 years, less frequent expression of BCL6 and a trend of more frequent expression of CD30 and pSTAT3 were found in patients with EBV+ DLBCL. In patients who are >50 years, common expression of CD30, p50, pSTAT3 and less frequent expression of BCL6 were observed. Older patients also more commonly had a poor performance status (ECOG≥2). Comparing EBV+ DLBCL patients in ≤50 years versus >50 years, both groups had similar clinicopathologic, immunophenotypic and genetic features. Gene expression profiling, microRNA profiling and treatment outcome of the younger patients with EBV+ DLBCL was not distinctive from tumors in older patients. Based on our data, we suggest that the arbitrary age cutoff for EBV+ DLBCL is unnecessary and should be eliminated in the WHO lymphoma classification scheme. PMID:26101854

  13. Differential regulation of mTOR signaling determines sensitivity to AKT inhibition in diffuse large B cell lymphoma

    PubMed Central

    Ezell, Scott A.; Wang, Suping; Bihani, Teeru; Lai, Zhongwu; Grosskurth, Shaun E.; Tepsuporn, Suprawee; Davies, Barry R.; Huszar, Dennis; Byth, Kate F.

    2016-01-01

    Agents that target components of the PI3K/AKT/mTOR pathway are under investigation for the treatment of diffuse large B cell lymphoma (DLBCL). Given the highly heterogeneous nature of DLBCL, it is not clear whether all subtypes of DLBCL will be susceptible to PI3K pathway inhibition, or which kinase within this pathway is the most favorable target. Pharmacological profiling of a panel of DLBCL cell lines revealed a subset of DLBCL that was resistant to AKT inhibition. Strikingly, sensitivity to AKT inhibitors correlated with the ability of these inhibitors to block phosphorylation of S6K1 and ribosomal protein S6. Cell lines resistant to AKT inhibition activated S6K1 independent of AKT either through upregulation of PIM2 or through activation by B cell receptor (BCR) signaling components. Finally, combined inhibition of AKT and BTK, PIM2, or S6K1 proved to be an effective strategy to overcome resistance to AKT inhibition in DLBCL. PMID:26824321

  14. MicroRNA-187 induces diffuse large B-cell lymphoma cell apoptosis via targeting BCL6

    PubMed Central

    HUANG, FANG; JIN, YAOFENG; WEI, YAFENG

    2016-01-01

    MicroRNAs (miRs) are endogenous non-coding RNAs that serve key functions in a wide range of biological processes, including cell growth, development, apoptosis and carcinogenesis. However, the association between miR-187 and B-cell lymphoma 6 (BCL6) has yet to be fully investigated in lymphoma cell apoptosis. The present study hypothesized that a post-translational mechanism may exist for BCL6 expression, which is regulated by miR-187 in lymphoma cells. The present study demonstrated that the expression of miR-187 in diffuse large B-cell lymphoma (DLBCL) cells was significantly decreased, and its expression was negatively correlated with BCL6 expression. It was also observed that miR-187 directly binds to the 3′-untranslated region of BCL6 mRNA and subsequently suppresses the expression of BCL6. Additionally, the induced expression of miR-187 significantly promoted DLBCL cell apoptosis in vitro. The drug sensitivity of human DLBCL SUDHL2 cells was increased following induction of miR-187 overexpression via an miR-187 mimic. In conclusion, the results of the present study suggest that the modulation of miR-187 expression in DLBCL cells may improve the sensitivity of chemotherapy through BCL6 targeting. PMID:27073562

  15. High-resolution copy number analysis of paired normal-tumor samples from diffuse large B cell lymphoma.

    PubMed

    Sebastián, Elena; Alcoceba, Miguel; Martín-García, David; Blanco, Óscar; Sanchez-Barba, Mercedes; Balanzategui, Ana; Marín, Luis; Montes-Moreno, Santiago; González-Barca, Eva; Pardal, Emilia; Jiménez, Cristina; García-Álvarez, María; Clot, Guillem; Carracedo, Ángel; Gutiérrez, Norma C; Sarasquete, M Eugenia; Chillón, Carmen; Corral, Rocío; Prieto-Conde, M Isabel; Caballero, M Dolores; Salaverria, Itziar; García-Sanz, Ramón; González, Marcos

    2016-01-01

    Copy number analysis can be useful for assessing prognosis in diffuse large B cell lymphoma (DLBCL). We analyzed copy number data from tumor samples of 60 patients diagnosed with DLBCL de novo and their matched normal samples. We detected 63 recurrent copy number alterations (CNAs), including 33 gains, 30 losses, and nine recurrent acquired copy number neutral loss of heterozygosity (CNN-LOH). Interestingly, 20 % of cases acquired CNN-LOH of 6p21 locus, which involves the HLA region. In normal cells, there were no CNAs but we observed CNN-LOH involving some key lymphoma regions such as 6p21 and 9p24.1 (5 %) and 17p13.1 (2.5 %) in DLBCL patients. Furthermore, a model with some specific CNA was able to predict the subtype of DLBCL, 1p36.32 and 10q23.31 losses being restricted to germinal center B cell-like (GCB) DLBCL. In contrast, 8p23.3 losses and 11q24.3 gains were strongly associated with the non-GCB subtype. A poor prognosis was associated with biallelic inactivation of TP53 or 18p11.32 losses, while prognosis was better in cases carrying 11q24.3 gains. In summary, CNA abnormalities identify specific DLBCL groups, and we describe CNN-LOH in germline cells from DLBCL patients that are associated with genes that probably play a key role in DLBCL development. PMID:26573278

  16. Distinct isoform of FABP7 revealed by screening for retroelement-activated genes in diffuse large B-cell lymphoma.

    PubMed

    Lock, Frances E; Rebollo, Rita; Miceli-Royer, Katharine; Gagnier, Liane; Kuah, Sabrina; Babaian, Artem; Sistiaga-Poveda, Maialen; Lai, C Benjamin; Nemirovsky, Oksana; Serrano, Isabel; Steidl, Christian; Karimi, Mohammad M; Mager, Dixie L

    2014-08-26

    Remnants of ancient transposable elements (TEs) are abundant in mammalian genomes. These sequences harbor multiple regulatory motifs and hence are capable of influencing expression of host genes. In response to environmental changes, TEs are known to be released from epigenetic repression and to become transcriptionally active. Such activation could also lead to lineage-inappropriate activation of oncogenes, as one study described in Hodgkin lymphoma. However, little further evidence for this mechanism in other cancers has been reported. Here, we reanalyzed whole transcriptome data from a large cohort of patients with diffuse large B-cell lymphoma (DLBCL) compared with normal B-cell centroblasts to detect genes ectopically expressed through activation of TE promoters. We have identified 98 such TE-gene chimeric transcripts that were exclusively expressed in primary DLBCL cases and confirmed several in DLBCL-derived cell lines. We further characterized a TE-gene chimeric transcript involving a fatty acid-binding protein gene (LTR2-FABP7), normally expressed in brain, that was ectopically expressed in a subset of DLBCL patients through the use of an endogenous retroviral LTR promoter of the LTR2 family. The LTR2-FABP7 chimeric transcript encodes a novel chimeric isoform of the protein with characteristics distinct from native FABP7. In vitro studies reveal a dependency for DLBCL cell line proliferation and growth on LTR2-FABP7 chimeric protein expression. Taken together, these data demonstrate the significance of TEs as regulators of aberrant gene expression in cancer and suggest that LTR2-FABP7 may contribute to the pathogenesis of DLBCL in a subgroup of patients. PMID:25114248

  17. Visceral adipose tissue is prognostic for survival of diffuse large B cell lymphoma treated with frontline R-CHOP.

    PubMed

    Shin, Dong-Yeop; Kim, Areumnuri; Byun, Byung Hyun; Moon, Hansol; Kim, Soyeun; Ko, Young-Jin; Kim, Min-Jung; Lee, Hyo-Rak; Kang, Hye-Jin; Na, Im Il; Park, Sunhoo; Lee, Seung Sook; Yang, Sung-Hyun

    2016-02-01

    The potential role of visceral adipose tissue (VAT) as a prognostic factor in patients with diffuse large B cell lymphoma (DLBCL) treated with frontline rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) immunochemotherapy was explored. Total adipose tissue and VAT were measured by analyzing positron emission tomography (PET)/computed tomography (CT) images obtained during the initial staging of patients with DLBCL. The VAT ratio was calculated as follows: VAT ratio = VAT area/total adipose tissue area. Body mass index (BMI), sex, and International Prognostic Index (IPI) were also incorporated as co-variates in the final model of multivariate Cox regression analysis for survival. A total of 156 patients with DLBCL, who were treated with frontline R-CHOP, were enrolled in our study. The median patient age was 61 years, and 81 patients were male (51.9 %). The median cycle of R-CHOP was six. The IPI risk group was a strong prognostic factor for progression-free survival (PFS) and overall survival (OS) (p < 0.001). Obese BMIs were an independent prognostic factor for PFS, but not for OS in multivariate analyses, compared to patients with normal BMIs (HR = 0.43, 95 % CI = 0.19-0.98, and p = 0.046 for PFS). A high VAT ratio (third tertile) was an independent adverse prognostic factor for PFS and OS in multivariate analyses (HR = 2.87 and 2.66, 95 % CI = 1.30-6.32 and 1.30-5.44, and p = 0.009 and 0.007 for PFS and OS, respectively). VAT ratio was an independent prognostic factor for patients with DLBCL treated with first-line R-CHOP; thus, additional large prospective studies are warranted. PMID:26658607

  18. Distinct isoform of FABP7 revealed by screening for retroelement-activated genes in diffuse large B-cell lymphoma

    PubMed Central

    Lock, Frances E.; Rebollo, Rita; Miceli-Royer, Katharine; Gagnier, Liane; Kuah, Sabrina; Babaian, Artem; Sistiaga-Poveda, Maialen; Lai, C. Benjamin; Nemirovsky, Oksana; Serrano, Isabel; Steidl, Christian; Karimi, Mohammad M.; Mager, Dixie L.

    2014-01-01

    Remnants of ancient transposable elements (TEs) are abundant in mammalian genomes. These sequences harbor multiple regulatory motifs and hence are capable of influencing expression of host genes. In response to environmental changes, TEs are known to be released from epigenetic repression and to become transcriptionally active. Such activation could also lead to lineage-inappropriate activation of oncogenes, as one study described in Hodgkin lymphoma. However, little further evidence for this mechanism in other cancers has been reported. Here, we reanalyzed whole transcriptome data from a large cohort of patients with diffuse large B-cell lymphoma (DLBCL) compared with normal B-cell centroblasts to detect genes ectopically expressed through activation of TE promoters. We have identified 98 such TE-gene chimeric transcripts that were exclusively expressed in primary DLBCL cases and confirmed several in DLBCL-derived cell lines. We further characterized a TE-gene chimeric transcript involving a fatty acid-binding protein gene (LTR2-FABP7), normally expressed in brain, that was ectopically expressed in a subset of DLBCL patients through the use of an endogenous retroviral LTR promoter of the LTR2 family. The LTR2-FABP7 chimeric transcript encodes a novel chimeric isoform of the protein with characteristics distinct from native FABP7. In vitro studies reveal a dependency for DLBCL cell line proliferation and growth on LTR2-FABP7 chimeric protein expression. Taken together, these data demonstrate the significance of TEs as regulators of aberrant gene expression in cancer and suggest that LTR2-FABP7 may contribute to the pathogenesis of DLBCL in a subgroup of patients. PMID:25114248

  19. Epstein-Barr virus-specific CD8(+) T lymphocytes from diffuse large B cell lymphoma patients are functionally impaired.

    PubMed

    Cárdenas, D; Vélez, G; Orfao, A; Herrera, M V; Solano, J; Olaya, M; Uribe, A M; Saavedra, C; Duarte, M; Rodríguez, M; López, M; Fiorentino, S; Quijano, S

    2015-11-01

    Epstein-Barr virus (EBV) is a persistent virus with oncogenic capacity that has been implicated in the development of aggressive B cell lymphomas, primarily in immunosuppressed individuals, although it can be present in immunocompetent individuals. Changes in the function and clonal diversity of T lymphocytes might be implied by viral persistence and lymphoma development. The aim of the present study was to evaluate the frequency, phenotype, function and clonotypical distribution of EBV-specific T cells after peripheral blood stimulation with a virus lysate in newly diagnosed patients with diffuse large B cell lymphoma (DLBCL) aged more than 50 years without prior histories of clinical immunosuppression compared with healthy controls. Our results showed impaired EBV-specific immune responses among DLBCL patients that were associated primarily with decreased numbers of central and effector memory CD8(+) T lymphocytes. In contrast to healthy controls, only a minority of the patients showed CD4(+)/tumour necrosis factor (TNF)-α(+) T cells expressing T cell receptor (TCR)-Vβ17 and CD8(+)/TNF-α(+) T cells with TCR-Vβ5·2, Vβ9 and Vβ18 in response to EBV. Notably, the production of TNF-α was undetectable among TCR-Vβ5·3(+), Vβ11(+), Vβ12(+), Vβ16(+) and Vβ23(+) CD8(+) T cells. In addition, we observed decreased numbers of CD4(+)/TNF-α(+) and CD8(+)/TNF-α(+), CD8(+)/interleukin (IL)-2(+) and CD8(+)/TNF-α(+)/IL-2(+) T lymphocytes in the absence of T cells capable of producing TNF-α, IL-2 and IFN-γ after EBV stimulation simultaneously. Moreover, DLBCL patients displayed higher IL-10 levels both under baseline conditions and after EBV stimulation. These findings were also observed in patients with positive EBV viral loads. Prospective studies including a large number of patients are needed to confirm these findings. PMID:26174440

  20. Generation of large-scale, barrier-free diffuse plasmas in air at atmospheric pressure using array wire electrodes and nanosecond high-voltage pulses

    SciTech Connect

    Teng, Yun; Li, Lee Liu, Yun-Long; Liu, Lun; Liu, Minghai

    2014-10-15

    This paper introduces a method to generate large-scale diffuse plasmas by using a repetition nanosecond pulse generator and a parallel array wire-electrode configuration. We investigated barrier-free diffuse plasmas produced in the open air in parallel and cross-parallel array line-line electrode configurations. We found that, when the distance between the wire-electrode pair is small, the discharges were almost extinguished. Also, glow-like diffuse plasmas with little discharge weakening were obtained in an appropriate range of line-line distances and with a cathode-grounding cross-electrode configuration. As an example, we produced a large-scale, stable diffuse plasma with volumes as large as 18 × 15 × 15 cm{sup 3}, and this discharge region can be further expanded. Additionally, using optical and electrical measurements, we showed that the electron temperature was higher than the gas temperature, which was almost the same as room temperature. Also, an array of electrode configuration with more wire electrodes had helped to prevent the transition from diffuse discharge to arc discharge. Comparing the current waveforms of configurations with 1 cell and 9 cells, we found that adding cells significantly increased the conduction current and the electrical energy delivered in the electrode gaps.

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

    SciTech Connect

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

    2014-01-14

    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.

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

    NASA Astrophysics Data System (ADS)

    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.

  3. Generation of large-scale, barrier-free diffuse plasmas in air at atmospheric pressure using array wire electrodes and nanosecond high-voltage pulses

    NASA Astrophysics Data System (ADS)

    Teng, Yun; Li, Lee; Liu, Yun-Long; Liu, Lun; Liu, Minghai

    2014-10-01

    This paper introduces a method to generate large-scale diffuse plasmas by using a repetition nanosecond pulse generator and a parallel array wire-electrode configuration. We investigated barrier-free diffuse plasmas produced in the open air in parallel and cross-parallel array line-line electrode configurations. We found that, when the distance between the wire-electrode pair is small, the discharges were almost extinguished. Also, glow-like diffuse plasmas with little discharge weakening were obtained in an appropriate range of line-line distances and with a cathode-grounding cross-electrode configuration. As an example, we produced a large-scale, stable diffuse plasma with volumes as large as 18 × 15 × 15 cm3, and this discharge region can be further expanded. Additionally, using optical and electrical measurements, we showed that the electron temperature was higher than the gas temperature, which was almost the same as room temperature. Also, an array of electrode configuration with more wire electrodes had helped to prevent the transition from diffuse discharge to arc discharge. Comparing the current waveforms of configurations with 1 cell and 9 cells, we found that adding cells significantly increased the conduction current and the electrical energy delivered in the electrode gaps.

  4. With and without: the bereavement experiences of gay men who have lost a partner to non-AIDS-related causes.

    PubMed

    Hornjatkevyc, Nina L

    2011-10-01

    This study gives voice to the experiences of gay men who have lost a partner to non-AIDS-related causes, a subject that has received little attention in the psychological literature. Interviews were conducted with 8 gay men. An analysis informed by hermeneutic phenomenology generated themes and contexualized meanings regarding the participants' diverse experiences. The themes identified areas of similarity and difference between the bereavement of these participants from those who have participated in general bereavement studies and from those who have lost a partner to AIDS. Implications for counseling practice and further research are discussed. PMID:24501836

  5. Recruiting Chinese American adolescents to HIV/AIDS-related research: a lesson learned from a cross-sectional study.

    PubMed

    Lee, Yi-Hui; Salman, Ali; Wang, Fan

    2012-02-01

    The purpose of this article was to report identified barriers and challenges experienced in the recruiting process of Chinese American adolescents to a cross-sectional HIV/AIDS-related study. Snowball sampling method was used to recruit Chinese American adolescents from Chinese American communities in a U.S. Midwestern state. Barriers and challenges to recruitment were reviewed and analyzed from Chinese cultural perspectives in the hope of aiding researchers and health care providers understand and facilitate future recruitment of Chinese Americans for HIV/AIDS prevention studies. Barriers to recruitment were found related to the taboo topic of sexual issues in Chinese culture, unawareness and denial of HIV/AIDS risks, authoritarian parenting style in Chinese culture, and the required active consents. Facilitating factors of recruiting Chinese American adolescents to future HIV/AIDS prevention research or intervention programs are discussed. Information provided in this article may increase nurses' awareness of various barriers that they might encounter when they conduct research or address HIV/AIDS-related topics of Chinese American adolescents. PMID:20974090

  6. Ethnobotanical Study of Plants Used in the Management of HIV/AIDS-Related Diseases in Livingstone, Southern Province, Zambia

    PubMed Central

    Chinsembu, Kazhila C.

    2016-01-01

    Faced with critical shortages of staff, long queues, and stigma at public health facilities in Livingstone, Zambia, persons who suffer from HIV/AIDS-related diseases use medicinal plants to manage skin infections, diarrhoea, sexually transmitted infections, tuberculosis, cough, malaria, and oral infections. In all, 94 medicinal plant species were used to manage HIV/AIDS-related diseases. Most remedies are prepared from plants of various families such as Combretaceae, Euphorbiaceae, Fabaceae, and Lamiaceae. More than two-thirds of the plants (mostly leaves and roots) are utilized to treat two or more diseases related to HIV infection. Eighteen plants, namely, Achyranthes aspera L., Lannea discolor (Sond.) Engl., Hyphaene petersiana Klotzsch ex Mart., Asparagus racemosus Willd., Capparis tomentosa Lam., Cleome hirta Oliv., Garcinia livingstonei T. Anderson, Euclea divinorum Hiern, Bridelia cathartica G. Bertol., Acacia nilotica Delile, Piliostigma thonningii (Schumach.) Milne-Redh., Dichrostachys cinerea (L.) Wight and Arn., Abrus precatorius L., Hoslundia opposita Vahl., Clerodendrum capitatum (Willd.) Schumach., Ficus sycomorus L., Ximenia americana L., and Ziziphus mucronata Willd., were used to treat four or more disease conditions. About 31% of the plants in this study were administered as monotherapies. Multiuse medicinal plants may contain broad-spectrum antimicrobial agents. However, since widely used plants easily succumb to the threats of overharvesting, they need special protocols and guidelines for their genetic conservation. There is still need to confirm the antimicrobial efficacies, pharmacological parameters, cytotoxicity, and active chemical ingredients of the discovered plants. PMID:27069489

  7. Ethnobotanical Study of Plants Used in the Management of HIV/AIDS-Related Diseases in Livingstone, Southern Province, Zambia.

    PubMed

    Chinsembu, Kazhila C

    2016-01-01

    Faced with critical shortages of staff, long queues, and stigma at public health facilities in Livingstone, Zambia, persons who suffer from HIV/AIDS-related diseases use medicinal plants to manage skin infections, diarrhoea, sexually transmitted infections, tuberculosis, cough, malaria, and oral infections. In all, 94 medicinal plant species were used to manage HIV/AIDS-related diseases. Most remedies are prepared from plants of various families such as Combretaceae, Euphorbiaceae, Fabaceae, and Lamiaceae. More than two-thirds of the plants (mostly leaves and roots) are utilized to treat two or more diseases related to HIV infection. Eighteen plants, namely, Achyranthes aspera L., Lannea discolor (Sond.) Engl., Hyphaene petersiana Klotzsch ex Mart., Asparagus racemosus Willd., Capparis tomentosa Lam., Cleome hirta Oliv., Garcinia livingstonei T. Anderson, Euclea divinorum Hiern, Bridelia cathartica G. Bertol., Acacia nilotica Delile, Piliostigma thonningii (Schumach.) Milne-Redh., Dichrostachys cinerea (L.) Wight and Arn., Abrus precatorius L., Hoslundia opposita Vahl., Clerodendrum capitatum (Willd.) Schumach., Ficus sycomorus L., Ximenia americana L., and Ziziphus mucronata Willd., were used to treat four or more disease conditions. About 31% of the plants in this study were administered as monotherapies. Multiuse medicinal plants may contain broad-spectrum antimicrobial agents. However, since widely used plants easily succumb to the threats of overharvesting, they need special protocols and guidelines for their genetic conservation. There is still need to confirm the antimicrobial efficacies, pharmacological parameters, cytotoxicity, and active chemical ingredients of the discovered plants. PMID:27069489

  8. Gray zone lymphoma with features intermediate between classical Hodgkin lymphoma and diffuse large B-cell lymphoma: characteristics, outcomes, and prognostication among a large multicenter cohort.

    PubMed

    Evens, Andrew M; Kanakry, Jennifer A; Sehn, Laurie H; Kritharis, Athena; Feldman, Tatyana; Kroll, Aimee; Gascoyne, Randy D; Abramson, Jeremy S; Petrich, Adam M; Hernandez-Ilizaliturri, Francisco J; Al-Mansour, Zeina; Adeimy, Camille; Hemminger, Jessica; Bartlett, Nancy L; Mato, Anthony; Caimi, Paolo F; Advani, Ranjana H; Klein, Andreas K; Nabhan, Chadi; Smith, Sonali M; Fabregas, Jesus C; Lossos, Izidore S; Press, Oliver W; Fenske, Timothy S; Friedberg, Jonathan W; Vose, Julie M; Blum, Kristie A

    2015-09-01

    Gray zone lymphoma (GZL) with features between classical Hodgkin lymphoma and diffuse large B-cell lymphoma (DLBCL) is a recently recognized entity reported to present primarily with mediastinal disease (MGZL). We examined detailed clinical features, outcomes, and prognostic factors among 112 GZL patients recently treated across 19 North American centers. Forty-three percent of patients presented with MGZL, whereas 57% had non-MGZL (NMGZL). NMGZL patients were older (50 versus 37 years, P = 0.0001); more often had bone marrow involvement (19% versus 0%, P = 0.001); >1 extranodal site (27% versus 8%, P = 0.014); and advanced stage disease (81% versus 13%, P = 0.0001); but they had less bulk (8% versus 44%, P = 0.0001), compared with MGZL patients. Common frontline treatments were cyclophosphamide-doxorubicin-vincristine-prednisone +/- rituximab (CHOP+/-R) 46%, doxorubicin-bleomycin-vinblastine-dacarbazine +/- rituximab (ABVD+/-R) 30%, and dose-adjusted etoposide-doxorubicin-cyclophosphamide-vincristine-prednisone-rituximab (DA-EPOCH-R) 10%. Overall and complete response rates for all patients were 71% and 59%, respectively; 33% had primary refractory disease. At 31-month median follow-up, 2-year progression-free survival (PFS) and overall survival rates were 40% and 88%, respectively. Interestingly, outcomes in MGZL patients seemed similar compared with that of NMGZL patients. On multivariable analyses, performance status and stage were highly prognostic for survival for all patients. Additionally, patients treated with ABVD+/-R had markedly inferior 2-year PFS (22% versus 52%, P = 0.03) compared with DLBCL-directed therapy (CHOP+/-R and DA-EPOCH-R), which persisted on Cox regression (hazard ratio, 1.88; 95% confidence interval, 1.03-3.83; P = 0.04). Furthermore, rituximab was associated with improved PFS on multivariable analyses (hazard ratio, 0.35; 95% confidence interval, 0.18-0.69; P = 0.002). Collectively, GZL is a heterogeneous

  9. Phase 2 study of panobinostat with or without rituximab in relapsed diffuse large B-cell lymphoma.

    PubMed

    Assouline, Sarit E; Nielsen, Torsten Holm; Yu, Stephen; Alcaide, Miguel; Chong, Lauren; MacDonald, David; Tosikyan, Axel; Kukreti, Vishal; Kezouh, Abbas; Petrogiannis-Haliotis, Tina; Albuquerque, Marco; Fornika, Daniel; Alamouti, Sepideh; Froment, Remi; Greenwood, Celia M T; Oros, Kathleen Klein; Camglioglu, Errol; Sharma, Ayushi; Christodoulopoulos, Rosa; Rousseau, Caroline; Johnson, Nathalie; Crump, Michael; Morin, Ryan D; Mann, Koren K

    2016-07-14

    The majority of diffuse large B-cell lymphoma (DLBCL) tumors contain mutations in histone-modifying enzymes (HMEs), indicating a potential therapeutic benefit of histone deacetylase inhibitors (HDIs), and preclinical data suggest that HDIs augment the effect of rituximab. In this randomized phase 2 study, we evaluated the response rate and toxicity of panobinostat, a pan-HDI administered 30 mg orally 3 times weekly, with or without rituximab, in 40 patients with relapsed or refractory de novo (n = 27) or transformed (n = 13) DLBCL. Candidate genes and whole exomes were sequenced in relapse tumor biopsies to search for molecular correlates, and these data were used to quantify circulating tumor DNA (ctDNA) in serial plasma samples. Eleven of 40 patients (28%) responded to panobinostat (95% confidence interval [CI] 14.6-43.9) and rituximab did not increase responses. The median duration of response was 14.5 months (95% CI 9.4 to "not reached"). At time of data censoring, 6 of 11 patients had not progressed. Of the genes tested for mutations, only those in MEF2B were significantly associated with response. We detected ctDNA in at least 1 plasma sample from 96% of tested patients. A significant increase in ctDNA at day 15 relative to baseline was strongly associated with lack of response (sensitivity 71.4%, specificity 100%). We conclude that panobinostat induces very durable responses in some patients with relapsed DLBCL, and early responses can be predicted by mutations in MEF2B or a significant change in ctDNA level at 15 days after treatment initiation. This clinical trial was registered at www.ClinicalTrials.gov (#NCT01238692). PMID:27166360

  10. Baseline renal function as a prognostic indicator in patients with newly diagnosed diffuse large B-cell lymphoma

    PubMed Central

    Hong, Junshik; Lee, Sojung; Chun, Gayoung; Jung, Ji Yong; Park, Jinny; Ahn, Jeong Yeal; Cho, Eun Kyung; Shin, Dong Bok

    2016-01-01

    Background The association between baseline renal impairment (RI) and the prognosis of diffuse large B-cell lymphoma (DLBCL) was previously not defined. The aim of this study was to evaluate the prognostic value of RI in patients with DLBCL treated with three-weekly rituximab plus cyclophosphamide, Adriamycin, vincristine, and prednisolone immunochemotherapy (R-CHOP21). Methods Patients with newly diagnosed de novo DLBCLs treated with ≥1 cycle of R-CHOP21 were analyzed retrospectively. Pretreatment blood samples were collected and the glomerular filtration rate (GFR) was calculated. RI was defined by a GFR of <60 mL/min/1.73 m2 according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. Results Of the 185 patients enrolled in the present study, 19 patients (10.3%) had RI. The reasons for baseline RI were pre-existing CKD (N=5), acute kidney injury due to either obstruction (N=2) or electrolyte imbalance (N=2) related to DLBCL, and undefined causes (N=10). Patients with baseline RI showed inferior overall survival (OS) compared to those without RI (P<0.001). In multivariate analysis, RI was identified as an International Prognostic Index (IPI)-independent prognostic indicator. A baseline hemoglobin level of <10 g/dL and the presence of RI effectively discriminated a portion of the patients with far inferior event-free survival and OS among the patients having high or high-intermediate risk cancers according to either the standard- or the National Comprehensive Cancer Network-IPI. Conclusion Pretreatment RI was an independent prognostic marker for inferior OS in patients with DLBCL treated with R-CHOP21 immunochemotherapy. PMID:27382556

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

    PubMed Central

    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

    2015-01-01

    Abstract 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. PMID:27347428

  12. Involved-Lesion Radiation Therapy After Chemotherapy in Limited-Stage Head-and-Neck Diffuse Large B Cell Lymphoma

    SciTech Connect

    Yu, Jeong Il; Nam, Heerim; Ahn, Yong Chan; Kim, Won Seog; Park, Keunchil; Kim, Seok Jin

    2010-10-01

    Purpose: To report treatment outcomes after combined-modality therapy in patients with Stage I/II head-and-neck (HN) diffuse large B cell lymphoma (DLBL). Methods and Materials: Eighty-six eligible patients received sequential chemotherapy and involved-lesion radiation therapy from 1995 to 2006. After a median of four cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or rituximab-plus-CHOP chemotherapy, a median of 41.4 Gy was delivered to the known initial gross lesion with adequate margin (2 to 3 cm). Results: After a median follow-up of 57 months, eight treatment failures were observed: distant metastasis in 8 patients; and locoregional failure in 4 patients. Among the 4 patients with locoregional failure, 3 presented with in-field failures, and 1 both in-field and out-of-field failure (contralateral neck). Rates of overall survival (OS) and freedom from progression (FFP) at 10 years were 74.1% and 88.9%, respectively. There was no severe side effect except 1 patient with Grade 3 mucositis during and after completion of radiation therapy. Multivariate analyses showed that absence of B symptom (p = 0.022) and normal lactate dehydrogenase (p = 0.017) were related to favorable OS, age >60 years (p = 0.033) was related to favorable FFP, and international prognostic index of 0 or 1 was related to favorable OS (p = 0.003) and FFP (p = 0.03). Conclusion: This study demonstrated that patients with Stage I/II HN DLBL did not need whole-neck irradiation. Involved-lesion radiation therapy might reduce radiation toxicity with favorable treatment results.

  13. A Strategy for Full Interrogation of Prognostic Gene Expression Patterns: Exploring the Biology of Diffuse Large B Cell Lymphoma

    PubMed Central

    Rimsza, Lisa M.; Unger, Joseph M.; Tome, Margaret E.; LeBlanc, Michael L.

    2011-01-01

    Background 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. Methodology/Principal Findings 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). Conclusions/Significance 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. PMID:21829609

  14. Primary bladder lymphoma, diffuse large B-cell type: Case report and literature review of 26 cases.

    PubMed

    Simpson, W Greg; Lopez, Armando; Babbar, Paurush; Payne, Lynnetta Faith

    2015-01-01

    Primary lymphoma of the urinary bladder is exceedingly rare, representing 0.2% of all extranodal non-Hodgkin's lymphoma. Although Matsuno et al. and others state the most common type is mucosa-associated lymphoid tissue (MALT) lymphoma, 20% of all the primary lymphomas of the urinary bladder are considered to be high grade neoplasms; the majority being diffuse large B-cell lymphoma (DLBCL). This is a case report of a 48-year-old man that presented with hematuria, frequency, nocturia, and flank pain that was found to have high grade DLBCL. Twenty-six other cases of both low and high grade primary bladder lymphomas were selected in order to provide a thorough comparison of different treatment modalities. Of the cases reviewed, bladder lymphoma was more common in females (2:1). The average age at diagnosis was 63.9 years old (low grade: 68.7 years old, high grade: 58.8 years old). The most common low-grade neoplasm was MALT lymphoma (85.7%). For the low-grade malignancies, the most successful treatments were simple therapies (2 transurethral resection of a bladder tumour [TURBT], 1 antibiotics), solitary chemotherapy, and combination TURBT/chemo; all 3 of which achieved 100% clinical remission (CR) in the cases reviewed. The most common high grade neoplasm was DLBCL (76.9%). The most successful therapies used to treat high grade lesions were solitary chemotherapy (cyclophosphamide, duanorubacin, vincristine, prednisolone [CHOP] or ritoximab, CHOP [R-CHOP]) and combination therapies (2 radiation/CHOP, 2 surgery/CHOP). In the agreement with the current literature, this review has shown that simple therapies (TURBT) are equally as effective as aggressive treatments (chemotherapy, radiation) and should therefore be used as first line treatment in low grade tumors. For high grade malignancies, chemotherapy (R-CHOP or CHOP) alone or combination therapy (CHOP/surgery or CHOP/radiation) is recommended. PMID:25837971

  15. High concordance of gene expression profiling-correlated immunohistochemistry algorithms in diffuse large B-cell lymphoma, not otherwise specified.

    PubMed

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

    2014-08-01

    Diffuse large B-cell lymphoma (DLBCL) is classified into prognostically distinct germinal center B-cell (GCB) and activated B-cell subtypes by gene expression profiling (GEP). Recent reports suggest the role of GEP subtypes in targeted therapy. Immunohistochemistry (IHC) algorithms have been proposed as surrogates of GEP, but their utility remains controversial. Using microarray, we examined the concordance of 4 GEP-correlated and 2 non-GEP-correlated IHC algorithms in 381 DLBCLs, not otherwise specified. Subtypes and variants of DLBCL were excluded to minimize the possible confounding effect on prognosis and phenotype. Survival was analyzed in 138 cyclophosphamide, adriamycin, vincristine, and prednisone (CHOP)-treated and 147 rituximab plus CHOP (R-CHOP)-treated patients. Of the GEP-correlated algorithms, high concordance was observed among Hans, Choi, and Visco-Young algorithms (total concordance, 87.1%; κ score: 0.726 to 0.889), whereas Tally algorithm exhibited slightly lower concordance (total concordance 77.4%; κ score: 0.502 to 0.643). Two non-GEP-correlated algorithms (Muris and Nyman) exhibited poor concordance. Compared with the Western data, incidence of the non-GCB subtype was higher in all algorithms. Univariate analysis showed prognostic significance for Hans, Choi, and Visco-Young algorithms and BCL6, GCET1, LMO2, and BCL2 in CHOP-treated patients. On multivariate analysis, Hans algorithm retained its prognostic significance. By contrast, neither the algorithms nor individual antigens predicted survival in R-CHOP treatment. The high concordance among GEP-correlated algorithms suggests their usefulness as reliable discriminators of molecular subtype in DLBCL, not otherwise specified. Our study also indicates that prognostic significance of IHC algorithms may be limited in R-CHOP-treated Asian patients because of the predominance of the non-GCB type. PMID:24705314

  16. Diminishing prognostic role of preexisting diabetes mellitus for patients with diffuse large B-cell lymphoma in the rituximab era.

    PubMed

    Lu, Hsueh-Ju; Huang, Yu-Chung; Liu, Chun-Yu; Hung, Man-Hsin; Hu, Ming-Hung; Wu, Chia-Yun; Hong, Ying-Chung; Hsiao, Liang-Tsai; Gau, Jyh-Pyng; Liu, Jin-Hwang; Hsu, Hui-Chi; Chiou, Tzeon-Jye; Tzeng, Cheng-Hwai; Yu, Yuan-Bin

    2013-11-01

    Rituximab reforms the treatment of diffuse large B-cell lymphoma (DLBCL) and the prognostic significance of baseline patient features should be reevaluated. Few population-based studies have investigated the association of diabetes mellitus (DM) and outcomes of lymphoma; however, the results remain inconclusive. From January 1, 2000 to December 31, 2009, a total of 468 consecutive newly diagnosed DLBCL patients receiving first-line chemotherapy with cyclophosphamide, vincristine, doxorubicin, and prednisolone (CHOP) or rituximab plus CHOP (R-CHOP) were enrolled. Pre-existing DM was defined according to medical history, use of antidiabetic medications, or any record of an abnormal hemoglobin A1c test. Progression-free survival (PFS) and overall survival (OS) were estimated and compared using the Kaplan-Meier method with a log-rank test. CHOP was administered in 194 patients, and 274 patients received R-CHOP. DM was identified in 16.2 % (76/468) of patients. Diabetic patients were older and more performance restricted, compared to the non-DM patients in both the CHOP and R-CHOP groups. In the CHOP group, 5-year PFS and OS were inferior in DM patients (PFS, 32.4 vs. 50.0 % (P = 0.039); OS, 38.2 vs. 62.5 % (P = 0.002)). However, outcomes were similar for both DM and non-DM patients in the context of R-CHOP treatment (PFS, 69.0 vs. 57.3 % (P = 0.179); OS, 76.2 vs. 69.8 % (P = 0.586)). The response rate of chemotherapy in DM patients was also improved to a level similar to non-DM patients with rituximab use. In conclusion, the prognostic significance of preexisting DM in DLBCL patients is changing in the rituximab era. The potentially additional benefit of rituximab in DM patients merits further investigation. PMID:23712292

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

    PubMed

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

    2016-05-01

    Gene expression profiling (GEP) had divided the diffuse large B-cell lymphoma (DLBCL) into molecular subgroups: germinal center B-cell like (GCB), activated B-cell like (ABC), and unclassified (UC) subtype. However, this classification with prognostic significance was not applied into clinical practice since there were more than 1000 genes to detect and interpreting was difficult. To classify cancer samples validly, eight significant genes (MYBL1, LMO2, BCL6, MME, IRF4, NFKBIZ, PDE4B, and SLA) were selected in 414 patients treated with CHOP/R-CHOP chemotherapy from Gene Expression Omnibus (GEO) data sets. Cutoffs for each gene were obtained using receiver-operating characteristic curves (ROC) new model based on the support vector machine (SVM) estimated the probability of membership into one of two subgroups: GCB and Non-GCB (ABC and UC). Furtherly, multivariate analysis validated the model in another two cohorts including 855 cases in all. As a result, patients in the training and validated cohorts were stratified into two subgroups with 94.0%, 91.0%, and 94.4% concordance with GEP, respectively. Patients with Non-GCB subtype had significantly poorer outcomes than that with GCB subtype, which agreed with the prognostic power of GEP classification. Moreover, the similar prognosis received in the low (0-2) and high (3-5) IPI scores group demonstrated that the new model was independent of IPI as well as GEP method. In conclusion, our new model could stratify DLBCL patients with CHOP/R-CHOP regimen matching GEP subtypes effectively. PMID:26869285

  18. Primary bladder lymphoma, diffuse large B-cell type: Case report and literature review of 26 cases

    PubMed Central

    Simpson, W. Greg; Lopez, Armando; Babbar, Paurush; Payne, Lynnetta Faith

    2015-01-01

    Primary lymphoma of the urinary bladder is exceedingly rare, representing 0.2% of all extranodal non-Hodgkin's lymphoma. Although Matsuno et al. and others state the most common type is mucosa-associated lymphoid tissue (MALT) lymphoma, 20% of all the primary lymphomas of the urinary bladder are considered to be high grade neoplasms; the majority being diffuse large B-cell lymphoma (DLBCL). This is a case report of a 48-year-old man that presented with hematuria, frequency, nocturia, and flank pain that was found to have high grade DLBCL. Twenty-six other cases of both low and high grade primary bladder lymphomas were selected in order to provide a thorough comparison of different treatment modalities. Of the cases reviewed, bladder lymphoma was more common in females (2:1). The average age at diagnosis was 63.9 years old (low grade: 68.7 years old, high grade: 58.8 years old). The most common low-grade neoplasm was MALT lymphoma (85.7%). For the low-grade malignancies, the most successful treatments were simple therapies (2 transurethral resection of a bladder tumour [TURBT], 1 antibiotics), solitary chemotherapy, and combination TURBT/chemo; all 3 of which achieved 100% clinical remission (CR) in the cases reviewed. The most common high grade neoplasm was DLBCL (76.9%). The most successful therapies used to treat high grade lesions were solitary chemotherapy (cyclophosphamide, duanorubacin, vincristine, prednisolone [CHOP] or ritoximab, CHOP [R-CHOP]) and combination therapies (2 radiation/CHOP, 2 surgery/CHOP). In the agreement with the current literature, this review has shown that simple therapies (TURBT) are equally as effective as aggressive treatments (chemotherapy, radiation) and should therefore be used as first line treatment in low grade tumors. For high grade malignancies, chemotherapy (R-CHOP or CHOP) alone or combination therapy (CHOP/surgery or CHOP/radiation) is recommended. PMID:25837971

  19. Germline variation in complement genes and event-free survival in follicular and diffuse large B-cell lymphoma.

    PubMed

    Charbonneau, Bridget; Maurer, Matthew J; Fredericksen, Zachary S; Zent, Clive S; Link, Brian K; Novak, Anne J; Ansell, Stephen M; Weiner, George J; Wang, Alice H; Witzig, Thomas E; Dogan, Ahmet; Slager, Susan L; Habermann, Thomas M; Cerhan, James R

    2012-09-01

    The complement pathway plays a central role in innate immunity, and also functions as a regulator of the overall immune response. We evaluated whether polymorphisms in complement genes are associated with event-free survival (EFS) in follicular lymphoma (FL) and diffuse large B-cell (DLBCL) lymphoma. We genotyped 167 single nucleotide polymorphisms (SNPs) from 30 complement pathway genes in a prospective cohort study of newly diagnosed FL (N = 107) and DLBCL (N = 82) patients enrolled at the Mayo Clinic from 2002 to 2005. Cox regression was used to estimate hazard ratios (HRs) for individual SNPs with EFS, adjusting for FLIPI or IPI and treatment. For gene-level analyses, we used a principal components based gene-level test. In gene-level analyses for FL EFS, CFH (P = 0.009), CD55 (P = 0.006), CFHR5 (P = 0.01), C9 (P = 0.02), CFHR1 (P = 0.03), and CD46 (P = 0.03) were significant at P < 0.05, and these genes remained noteworthy after accounting for multiple testing (q < 0.15). SNPs in CFH, CFHR1, and CFHR5 showed stronger associations among patients receiving any rituximab, while SNPs from CD55 and CD46 showed stronger associations among patients who were observed. For DLBCL, only CLU (P = 0.001) and C7 (P = 0.03) were associated with EFS, but did not remain noteworthy after accounting for multiple testing (q>0.15). Genes from the regulators of complement activation (CFH, CD55, CFHR1, CFHR5, CD46) at 1q32-q32.1, along with C9, were associated with FL EFS after adjusting for clinical variables, and if replicated, these findings add further support for the role of host innate immunity in FL prognosis. PMID:22718493

  20. Epstein-Barr virus-positive diffuse large B-cell lymphoma association is not only restricted to elderly patients.

    PubMed

    Cohen, M; Narbaitz, M; Metrebian, F; De Matteo, E; Preciado, M V; Chabay, P A

    2014-12-15

    Diffuse large B-cell lymphoma (DLBCL), the most common group of malignant lymphomas, account for 30% of adult non-Hodgkin lymphomas. The 2008 World Health Organization (WHO) classification included a new entity, Epstein-Barr virus (EBV)+ DLBCL of the elderly, affecting patients aged 50 years or older. However, some reports of younger EBV+ DLBCL cases, without evidence of underlying immunosuppression, can be found. The role of EBV in tumor microenvironment composition in DLBCL is still not well understood. Our aim was to assess EBV presence and latency pattern as well as tumor T-cell population in an adult DLBCL series of Argentina. The study was conducted on biopsies from 75 DLBCL patients. EBERs expression was performed by in situ hybridization, while EBV gene expression was analyzed using real-time polymerase chain reaction. LMP1, LMP2A, EBNA2, EBNA3A, CD4, CD8 and Foxp3 expression was assessed by immunohistochemistry. Nine percent of cases showed EBV expression, with similar frequency among patients younger than 50 years and 50 years or older (13% and 8%, respectively). T-cell subsets were not altered by EBV presence. Latency type II was the most frequently observed, together with lytic gene expression in EBV+ DLBCL, with ≥20% of EBERs+ cells. These findings suggest that EBV+ DLBCL in our series was similar to the previously described in Asia and Latin-America, displaying latency II or III expression profile and no age-specific characteristics. Finally, EBV+ DLBCL may be an entity that is not only restricted to patients who are older than 50 years of age, in consequence the age cutoff revision may be a current goal. PMID:24789501

  1. SUVmax reduction improves early prognosis value of interim positron emission tomography scans in diffuse large B-cell lymphoma.

    PubMed

    Casasnovas, René-Olivier; Meignan, Michel; Berriolo-Riedinger, Alina; Bardet, Stéphane; Julian, Anne; Thieblemont, Catherine; Vera, Pierre; Bologna, Serge; Brière, Josette; Jais, Jean-Philippe; Haioun, Corinne; Coiffier, Bertrand; Morschhauser, Franck

    2011-07-01

    The prognostic value of interim positron emission tomography (PET) interpreted according to visual criteria is a matter of debate in diffuse large B-cell lymphoma (DLBCL). Maximal standardized uptake value reduction (ΔSUVmax) may better predict outcome. To compare the prognostic value of both methods, we analyzed PET done at baseline (PET0) and after 2 (PET2) and 4 (PET4) cycles in 85 patients with high-risk DLBCL enrolled on a prospective multicenter trial. All images were centrally reviewed and interpreted visually according to the International Harmonization Project criteria and by computing ΔSUVmax between PET0 and PET2 (ΔSUVmaxPET0-2) or PET4 (ΔSUVmaxPET0-4). Optimal cutoff to predict progression or death was 66% for ΔSUVmaxPET0-2 and 70% for ΔSUVmaxPET0-4. Outcomes did not differ significantly whether PET2 and PET4 were visually positive or negative. Inversely, ΔSUVmaxPET0-2 analysis (> 66% vs ≤ 66%) identified patients with significantly different 2-year progression-free survival (77% vs 57%; P = .0282) and overall survival (93% vs 60%; P < .0001). ΔSUVmaxPET0-4 analysis (> 70% vs ≤ 70%) seemed even more predictive for 2-year progression-free survival (83 vs 40%; P < .0001) and overall survival (94% vs 50%; P < .0001). ΔSUVmax analysis of sequential interim PET is feasible for high-risk DLBCL and better predicts outcome than visual analysis. The trial was registered at http://clinicaltrials.gov as NCT00498043. PMID:21518924

  2. Improving survival and preventing recurrence of diffuse large B-cell lymphoma in younger patients: current strategies and future directions

    PubMed Central

    Karlin, Lionel; Coiffier, Bertrand

    2013-01-01

    Prognosis of diffuse large B-cell lymphoma (DLBCL) has considerably improved during the last decade, mainly due to the addition of rituximab to chemotherapy. However, a significant proportion of patients still experience primary refractory disease or short-term relapses, conferring poor survival. Thus, achieving first-line complete remission is of major importance, especially in young and fit patients. Current strategies are based on the age-adapted International Prognostic Index, which separates patients into three prognostic subgroups (low-risk, intermediate-risk, and high-risk). However, it is based only on clinical variables, and we have learned from daily practice that there remains a marked heterogeneity within each subgroup. Recently, biological prognostic factors have emerged, and should now be part of initial evaluation to guide treatment. Among those, so-called double-hit DLBCL with deregulation of both MYC and BCL2 genes usually follows a particularly aggressive course and should be treated more intensively. But for many other patients, the indication of high-dose therapy rather than immunochemotherapy alone remains controversial. In these cases, the interest of an early 18F fluoro-2-deoxy-d-glucose positron emission tomography evaluation-based strategy is now being assessed in ongoing clinical trials. Moreover, other strategies to improve response and survival consist in adding novel agents to standard chemotherapy. In this field, newly developed anti-CD20 monoclonal antibodies and immunomodulatory drugs could be of particular interest during induction therapy to optimize the quality of response, but also in maintenance treatment, in order to decrease the risk of relapse. Only well-conducted clinical trials will be able to resolve all these issues. Therefore, physicians should be encouraged, as far as possible, to propose them to their patients. PMID:23579927

  3. Chromosome instability in diffuse large B cell lymphomas is suppressed by activation of the noncanonical NF-κB pathway

    PubMed Central

    Ramachandiran, Sampath; Adon, Arsene; Guo, Xiangxue; Wang, Yi; Wang, Huichen; Chen, Zhengjia; Kowalski, Jeanne; Sunay, Ustun R.; Young, Andrew N.; Brown, Theresa; Mar, Jessica C.; Du, Yuhong; Fu, Haian; Mann, Karen P.; Natkunam, Yasodha; Boise, Lawrence H.; Saavedra, Harold I.; Lossos, Izidore S.; Bernal-Mizrachi, Leon

    2016-01-01

    Diffuse large B cell lymphoma (DLBCL) is the most common form of lymphoma in the United States. DLBCL comprises biologically distinct subtypes including germinal center-like (GCB) and activated-B-cell-like DLBCL (ABC). The most aggressive type, ABC-DLBCL, displays dysregulation of both canonical and noncanonical NF-κB pathway as well as genomic instability. Although, much is known about the tumorigenic roles of the canonical NF-kB pathway, the precise role of the noncanonical NF-kB pathway remains unknown. Here we show that activation of the noncanonical NF-κB pathway regulates chromosome stability, DNA damage response and centrosome duplication in DLBCL. Analysis of 92 DLBCL samples revealed that activation of the noncanonical NF-κB pathway is associated with low levels of DNA damage and centrosome amplification. Inhibiting the noncanonical pathway in lymphoma cells uncovered baseline DNA damage and prevented doxorubicin-induced DNA damage repair. In addition, it triggered centrosome amplification and chromosome instability, indicated by anaphase bridges, multipolar spindles and chromosome missegregation. We determined that the noncanonical NF-κB pathway execute these functions through the regulation of GADD45α and REDD1 in a p53-independent manner, while it collaborates with p53 to regulate cyclin G2 expression. Furthermore, this pathway regulates GADD45α, REDD1 and cyclin G2 through direct binding of NF-κB sites to their promoter region. Overall, these results indicate that the noncanonical NF-κB pathway plays a central role in maintaining genome integrity in DLBCL. Our data suggests that inhibition of the noncanonical NF-kB pathway should be considered as an important component in DLBCL therapeutic approach. PMID:25359525

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

    PubMed

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

    2016-08-01

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

  5. Novel prognostic genes of diffuse large B-cell lymphoma revealed by survival analysis of gene expression data

    PubMed Central

    Li, Chenglong; Zhu, Biao; Chen, Jiao; Huang, Xiaobing

    2015-01-01

    Objective This study aimed to identify prognostic genes for diffuse large B-cell lymphoma (DLBCL), using bioinformatic methods. Methods Five gene expression data sets were downloaded from the Gene Expression Omnibus database. Significance analysis of microarrays algorithm was used to identify differentially expressed genes (DEGs) from two data sets. Functional enrichment analysis was performed for the DEGs with the Database for Annotation, Visualization and Integration Discovery (DAVID). Survival analysis was performed with the Kaplan–Meier method using function survfit from package survival of R for the other three data sets. Cox univariate regression analysis was used to further screen out prognostic genes. Results Thirty-one common DEGs were identified in the two data sets, mainly enriched in the regulation of lymphocyte activation, immune response, and interleukin-mediated signaling pathway. Combined with 47 DLBCL-related genes acquired by literature retrieval, a total of 78 potential prognostic genes were obtained. Cases from the other three data sets were used in hierarchical clustering, and the 78 genes could cluster them into several subtypes with significant differences in survival curves. Cox univariate regression analysis revealed 45, 33, and eleven prognostic genes in the three data sets, respectively. Five common prognostic genes were revealed, including LCP2, TNFRSF9, FUT8, IRF4, and TLE1, among which LCP2, FUT8, and TLE1 were novel prognostic genes. Conclusion Five prognostic genes of DLBCL were identified in this study. They could not only be used for molecular subtyping of DLBCL but also be potential targets for treatment. PMID:26604798

  6. Reconstruction of canine diffuse large B-cell lymphoma gene regulatory network: detection of functional modules and hub genes.

    PubMed

    Zamani-Ahmadmahmudi, M; Najafi, A; Nassiri, S M

    2015-01-01

    Lymphoma is one of the most common malignancies in dogs. Canine lymphoma is similar to human non-Hodgkin's lymphoma (NHL) with shared clinical presentation and histopathological features. This study reports the construction of a comprehensive gene regulatory network (GRN) for canine diffuse large B-cell lymphoma (DLBCL), the most common type of canine lymphoma, and performs analysis for detection of major functional modules and hub genes (the most important genes in a GRN). The canine DLBCL GRN was reconstructed from gene expression data (NCBI GEO dataset: GSE30881) using the STRING and MiMI interaction databases. Reconstructed GRNs were then assessed, using various bioinformatics programmes, in order to analyze network topology and identify major pathways and hub genes. The resultant network from both interaction databases had a logically scale-free pattern. Gene ontology (GO) analysis revealed cell activation, cell cycle phase, immune effector process, immune system development, immune system process, integrin-mediated signalling pathway, intracellular protein kinase cascade, intracellular signal transduction, leucocyte activation and differentiation, lymphocyte activation and differentiation as major GO terms in the biological processes of the networks. Moreover, bioinformatics analysis showed E2F1, E2F4, PTEN, CDKN1A, PCNA, DKC1, MNAT1, NDUFB4, ATP5J, PRKDC, BRCA1, MYCN, RFC4 and POLA1 as the most important hub genes. The phosphatidyl inositol signalling system, P53 signalling pathway, Rac CycD pathway, G1/S checkpoint, chemokine signalling pathway and telomere maintenance were the main signalling pathways in which the protein products of the hub genes are involved. PMID:25678421

  7. Phase 2 study of panobinostat with or without rituximab in relapsed diffuse large B-cell lymphoma

    PubMed Central

    Nielsen, Torsten Holm; Yu, Stephen; Alcaide, Miguel; Chong, Lauren; MacDonald, David; Tosikyan, Axel; Kukreti, Vishal; Kezouh, Abbas; Petrogiannis-Haliotis, Tina; Albuquerque, Marco; Fornika, Daniel; Alamouti, Sepideh; Froment, Remi; Greenwood, Celia M. T.; Oros, Kathleen Klein; Camglioglu, Errol; Sharma, Ayushi; Christodoulopoulos, Rosa; Rousseau, Caroline; Johnson, Nathalie; Crump, Michael; Morin, Ryan D.; Mann, Koren K.

    2016-01-01

    The majority of diffuse large B-cell lymphoma (DLBCL) tumors contain mutations in histone-modifying enzymes (HMEs), indicating a potential therapeutic benefit of histone deacetylase inhibitors (HDIs), and preclinical data suggest that HDIs augment the effect of rituximab. In this randomized phase 2 study, we evaluated the response rate and toxicity of panobinostat, a pan-HDI administered 30 mg orally 3 times weekly, with or without rituximab, in 40 patients with relapsed or refractory de novo (n = 27) or transformed (n = 13) DLBCL. Candidate genes and whole exomes were sequenced in relapse tumor biopsies to search for molecular correlates, and these data were used to quantify circulating tumor DNA (ctDNA) in serial plasma samples. Eleven of 40 patients (28%) responded to panobinostat (95% confidence interval [CI] 14.6-43.9) and rituximab did not increase responses. The median duration of response was 14.5 months (95% CI 9.4 to “not reached”). At time of data censoring, 6 of 11 patients had not progressed. Of the genes tested for mutations, only those in MEF2B were significantly associated with response. We detected ctDNA in at least 1 plasma sample from 96% of tested patients. A significant increase in ctDNA at day 15 relative to baseline was strongly associated with lack of response (sensitivity 71.4%, specificity 100%). We conclude that panobinostat induces very durable responses in some patients with relapsed DLBCL, and early responses can be predicted by mutations in MEF2B or a significant change in ctDNA level at 15 days after treatment initiation. This clinical trial was registered at www.ClinicalTrials.gov (#NCT01238692). PMID:27166360

  8. Oncogenic CARMA1 couples NF-κB and β-catenin signaling in diffuse large B-cell lymphomas

    PubMed Central

    Bognar, M K; Vincendeau, M; Erdmann, T; Seeholzer, T; Grau, M; Linnemann, J R; Ruland, J; Scheel, C H; Lenz, P; Ott, G; Lenz, G; Hauck, S M; Krappmann, D

    2016-01-01

    Constitutive activation of the antiapoptotic nuclear factor-κB (NF-κB) signaling pathway is a hallmark of the activated B-cell-like (ABC) subtype of diffuse large B-cell lymphomas (DLBCL). Recurrent oncogenic mutations are found in the scaffold protein CARMA1 (CARD11) that connects B-cell receptor (BCR) signaling to the canonical NF-κB pathway. We asked how far additional downstream processes are activated and contribute to the oncogenic potential of DLBCL-derived CARMA1 mutants. To this end, we expressed oncogenic CARMA1 in the NF-κB negative DLBCL lymphoma cell line BJAB. By a proteomic approach we identified recruitment of β-catenin and its destruction complex consisting of APC, AXIN1, CK1α and GSK3β to oncogenic CARMA1. Recruitment of the β-catenin destruction complex was independent of CARMA1-BCL10-MALT1 complex formation or constitutive NF-κB activation and promoted the stabilization of β-catenin. The β-catenin destruction complex was also recruited to CARMA1 in ABC DLBCL cell lines, which coincided with elevated β-catenin expression. In line, β-catenin was frequently detected in non-GCB DLBCL biopsies that rely on chronic BCR signaling. Increased β-catenin amounts alone were not sufficient to induce classical WNT target gene signatures, but could augment TCF/LEF-dependent transcriptional activation in response to WNT signaling. In conjunction with NF-κB, β-catenin enhanced expression of immunosuppressive interleukin-10 and suppressed antitumoral CCL3, indicating that β-catenin can induce a favorable tumor microenvironment. Thus, parallel activation of NF-κB and β-catenin signaling by gain-of-function mutations in CARMA1 augments WNT stimulation and is required for regulating the expression of distinct NF-κB target genes to trigger cell-intrinsic and extrinsic processes that promote DLBCL lymphomagenesis. PMID:26776161

  9. Towards Better Simple Stellar Population Modeling of Active Galaxies Using Diffusion K-Means and the Southern African Large Telescope

    NASA Astrophysics Data System (ADS)

    Mosby, Gregory; Wold, I.; Sheinis, A.; Richards, J.

    2012-01-01

    We now know that most galaxies have supermassive black holes in their centers, and somewhat unexpectedly, there are relationships--such as the M-sigma relation--between the mass of the central black hole and the velocity dispersion of the host galaxy's stellar spheroid (bulge), even though they lie outside the black hole's influence. Galaxy merger models show reasonable evidence for coevolution of the bulge and black hole since the merging process initiates simultaneous growth of the black hole and galaxy by supplying gas to the nucleus for accretion onto the black hole and triggering bursts of star formation. The merging process truncates the growth of both by removing the gas reservoir via feedback from these processes. However, it's very difficult to observationally test such models on objects at the peak of black hole growth--during the quasar phase, when the central nucleus outshines the host galaxy. But, by using 3-d spectroscopy methods, namely integral field units (IFUs), we have shown that it is possible to successfully recover information about the host galaxy's integrated star formation history that can be used to check merger-induced galaxy evolution predicted by the models. This research focuses on more reliably decomposing AGN host galaxy spectra into simple stellar populations (SSPs) using a statistical method called diffusion k-means. And in effort to advance this topic further with new instrumentation, this research also involves testing and development of the detector for the near infrared arm of the Robert Stobie Spectrograph (RSS) for the newly commissioned 11-meter Southern African Large Telescope (SALT).

  10. A microRNA signature profile in EBV+ diffuse large B-cell lymphoma of the elderly

    PubMed Central

    de Andrade, Tathiana Azevedo; Evangelista, Adriane Feijo; Campos, Antonio Hugo Froes; Poles, Wagner Augusto; Borges, Natalia Morais; Camillo, Claudia Malheiros Coutinho; Soares, Fernando Augusto; Vassallo, Jose; Paes, Roberto Pinto; Zerbini, Maria Claudia; Scapulatempo, Cristovam; Alves, Antonio Correa

    2014-01-01

    Currently, there is no characteristic microRNA (miRNA) expression pattern in Epstein-Barr virus+ diffuse large B-cell lymphoma of the elderly (EBV+DLBCLe). This study aims to characterize a signature profile and identify miRNAs that can be used as biomarkers and alternative therapeutic targets for EBV+DLBCLe. Seventy-one DLBCL patients aged 50 years and older were included and four EBV+ and four EBV– samples were analyzed in two miRNA array platforms (pilot study). A larger multicenter cohort (29 EBV+DLBCLe and 65 EBV–DLBCL patients) was used to validate the results by real-time polymerase chain reaction. In the pilot study, 9% of DLBCL were EBV+DLBCLe by in situ hybridization. In multicenter study, EBV+DLBCLe group showed a predominance of non-germinal center B-cell origin. Overall survival duration of EBV+DLBCLe was significantly inferior to that of EBV–DLBCL patients. We found 10 deregulated miRNAs in the two groups, but only seven were statistically different. We confirmed overexpression of hsa-miR-126, hsa-miR-146a, hsa-miR-146b, hsa-miR-150, and hsa-miR-222 and underexpression of hsa-miR-151 in EBV+DLBCLe cases compared to EBV–DLBCL cases. Hsa-miR-146b and hsa-miR-222 showed high specificity for identifying EBV+DLBCLe. The present study proposed a miRNA signature for EBV+DLBCLe and our findings suggest that hsa-miR-146b and hsa-miR-222 could be biomarkers and therapeutic targets. PMID:25544772

  11. Gallium-67 imaging: A predictor of residual tumor viability and clinical outcome in patients with diffuse large-cell lymphoma

    SciTech Connect

    Kaplan, W.D.; Jochelson, M.S.; Herman, T.S.; Nadler, L.M.; Stomper, P.C.; Takvorian, T.; Andersen, J.W.; Canellos, G.P. )

    1990-12-01

    Durable complete remissions (CRs) can be achieved in patients with diffuse large-cell lymphoma (DLCL) with multidrug chemotherapy. The length of time to reach CR may be predictive of treatment outcome. However, defining CR by chest radiograph or computed tomography (CT) is often difficult since residual abnormalities do not always indicate residual disease. We have prospectively evaluated the ability of gallium-67 citrate (Ga-67) imaging to define residual disease and predict outcome in 37 consecutive patients with DLCL. Patients received 296 to 370 megabecquerels (MBq) Ga-67 and were imaged prior to, following cycles 4 to 6, and at completion of intensive chemotherapy. Ga-67 scan results were correlated with radiographic studies. Seventeen of 37 patients (46%) showed persistent, abnormal Ga-67 uptake halfway through chemotherapy. Of these, four were in CR, 11 were in partial remission (PR), and two showed no change in tumor size. At follow-up, 10 (59%) have died (three who were scored as CR and seven who were in PR halfway through therapy), two are alive with active tumor, one relapsed and survives following bone marrow transplant, and four (three in PR and one in CR at the therapeutic halfway point) are without disease at a median of 28 months from presentation. Of the 20 patients who were Ga-67-negative halfway through therapy, 11 were in CR and nine were in PR. Five of 20 patients (25%) have died. Three, in radiographic CR died at 11, 26, and 28 months, and two in radiographic PR died at 15 and 17 months. One patient is alive with active tumor, and 14 patients (70%) are alive without disease at a median of 34 months from presentation. Ga-67 imaging proved to be an excellent indicator of residual viable tumor; a positive scan halfway through therapy predicted for a poor outcome and may well justify a change in treatment.

  12. Super-SILAC Allows Classification of Diffuse Large B-cell Lymphoma Subtypes by Their Protein Expression Profiles*

    PubMed Central

    Deeb, Sally J.; D'Souza, Rochelle C. J.; Cox, Jürgen; Schmidt-Supprian, Marc; Mann, Matthias

    2012-01-01

    Correct classification of cancer patients into subtypes is a prerequisite for acute diagnosis and effective treatment. Currently this classification relies mainly on histological assessment, but gene expression analysis by microarrays has shown great promise. Here we show that high accuracy, quantitative proteomics can robustly segregate cancer subtypes directly at the level of expressed proteins. We investigated two histologically indistinguishable subtypes of diffuse large B-cell lymphoma (DLBCL): activated B-cell-like (ABC) and germinal-center B-cell-like (GCB) subtypes, by first developing a general lymphoma stable isotope labeling with amino acids in cell culture (SILAC) mix from heavy stable isotope-labeled cell lines. This super-SILAC mix was combined with cell lysates from five ABC-DLBCL and five GCB-DLBCL cell lines. Shotgun proteomic analysis on a linear ion trap Orbitrap mass spectrometer with high mass accuracy at the MS and MS/MS levels yielded a proteome of more than 7,500 identified proteins. High accuracy of quantification allowed robust separation of subtypes by principal component analysis. The main contributors to the classification included proteins known to be differentially expressed between the subtypes such as the transcription factors IRF4 and SPI1/PU.1, cell surface markers CD44 and CD27, as well as novel candidates. We extracted a signature of 55 proteins that segregated subtypes and contained proteins connected to functional differences between the ABC and GCB-DLBCL subtypes, including many NF-κB-regulated genes. Shortening the analysis time to single-shot analysis combined with use of the new linear quadrupole Orbitrap analyzer (Q Exactive) also clearly differentiated between the subtypes. These results show that high resolution shotgun proteomics combined with super-SILAC-based quantification is a promising new technology for tumor characterization and classification. PMID:22442255

  13. T-cell leukemia 1 expression in nodal Epstein-Barr virus-negative diffuse large B-cell lymphoma and primary mediastinal B-cell lymphoma.

    PubMed

    Gualco, Gabriela; Weiss, Lawrence M; Barber, Glen N; Bacchi, Carlos E

    2010-09-01

    The physiologic expression of the product of the proto-oncogene TCL1 (T-cell leukemia 1) is primarily restricted to early embryonic cells. In nonneoplastic B cells, the expression of TCL1 is determined by the differentiation step with silencing at the germinal center stage. TCL1 protein is overexpressed in a wide variety of human diseases. It has been shown that TCL1 is a powerful B-cell oncogene, which has been implicated in the pathogenesis of various types of mature B-cell lymphomas. There is no comparative information in the literature addressing the expression of TCL1 in pediatric and adult nodal diffuse large B-cell lymphoma or primary mediastinal large B-cell lymphoma. We studied 55 cases of adult and pediatric diffuse large B-cell lymphoma and primary mediastinal large B-cell lymphoma to analyze the phenotypic profile of these lymphomas, including TCL1 expression, and its relationship with clinical outcome in different age groups. The cases were analyzed by immunohistochemistry for the expression of TCL1, CD10, BCL-2, BCL-6, and MUM1. We also evaluated c-MYC translocation by fluorescence in situ hybridization. TCL1 was observed in 11 cases, 5 pediatric and 6 adult cases, all but one diffuse large B-cell lymphoma. Pediatric cases showed a significant association between TCL1 expression, high proliferative index, and presence of c-MYC translocation. TCL1 positivity was predominantly found in germinal center phenotype diffuse large B-cell lymphoma. Overall survival was worse in adult TCL1-positive cases than pediatric ones. Primary mediastinal large B-cell lymphomas infrequently expressed TCL1 in both age groups. PMID:20382409

  14. Exploratory investigation of the use of area suction to eliminate air-flow separation in diffusers having large expansion angles

    NASA Technical Reports Server (NTRS)

    Holzhauser, Curt A; Hall, Leo P

    1956-01-01

    Tests were made at a mean inlet Mach number of 0.2 with area suction applied to conical diffusers with expansion angles of 30 degrees and 50 degrees and exit to inlet area ratios of 2. Air-flow separation was eliminated with suction mass flows of 3 and 4 percent of the inlet mass flows for the 30 degrees and 50 degrees diffusers, respectively.

  15. AIDS-Related Stigma and Mental Disorders among People Living with HIV: A Cross-Sectional Study in Cambodia

    PubMed Central

    Yi, Siyan; Chhoun, Pheak; Suong, Samedy; Thin, Kouland; Brody, Carinne; Tuot, Sovannary

    2015-01-01

    Background AIDS-related stigma and mental disorders are the most common conditions in people living with HIV (PLHIV). We therefore conducted this study to examine the association of AIDS-related stigma and discrimination with mental disorders among PLHIV in Cambodia. Methods A two-stage cluster sampling method was used to select 1,003 adult PLHIV from six provinces. The People Living with HIV Stigma Index was used to measure stigma and discrimination, and a short version of general health questionnaire (GHQ-12) was used to measure mental disorders. Multivariate logistic regression analysis was conducted. Results The reported experiences of discrimination in communities in the past 12 months ranged from 0.8% for reports of being denied health services to 42.3% for being aware of being gossiped about. Internal stigma was also common ranging from 2.8% for avoiding going to a local clinic and/or hospital to 59.6% for deciding not to have (more) children. The proportions of PLHIV who reported fear of stigma and discrimination ranged from 13.9% for fear of being physically assaulted to 34.5% for fear of being gossiped about. The mean score of GHQ-12 was 3.2 (SD = 2.4). After controlling for several potential confounders, higher levels of mental disorders (GHQ-12≥ 4) remained significantly associated with higher levels of experiences of stigma and discrimination in family and communities (AOR = 1.9, 95% CI = 1.4–2.6), higher levels of internal stigma (AOR = 1.7, 95% CI = 1.2–2.3), and higher levels of fear of stigma and discrimination in family and communities (AOR = 1.5, 95% CI = 1.1–2.2). Conclusions AIDS-related stigma and discrimination among PLHIV in Cambodia are common and may have potential impacts on their mental health conditions. These findings indicate a need for community-based interventions to reduce stigma and discrimination in the general public and to help PLHIV to cope with this situation. PMID:25806534

  16. Amphotericin B lipid complex available for AIDS related cryptococcal meningitis. South Africa.

    PubMed

    1993-10-11

    Amphotericin B is generally considered to be the standard treatment against candidiasis, cryptococcal meningitis, and aspergillosis. The potential side effects of kidney toxicity and anemia, however, limit its use. Amphotericin B has therefore been incorporated into a lipid complex and clinical results thus far suggest that this ensemble may significantly reduce the risk of toxicity while maintaining or increasing drug efficacy. This modified version of amphotericin B (ABLC) is available on a compassionate use basis in the US and Europe for patients with life-threatening systemic fungal infections for whom currently marketed drugs are ineffective or too toxic. 250 patients have thus far been treated with ABLC under the compassionate use program; several hundred more have received it in controlled clinical trials; and additional large US phase 3 trials are being planned. The Liposome Company, Inc., of Princeton, New Jersey, has initiated named patient distribution of ABLC in the Republic of South Africa. 2 patients with cryptococcal meningitis have thus far received it. Cryptococcal meningitis is a type of fungal infection occurring in up to 10% of patients with AIDS; 20% of patients die within 30 days of diagnosis. The chairman and CEO of Liposome argues that getting the drug to AIDS patients in South Africa will help the company accumulate data quickly on the drug's efficacy and safety. The company is also working upon an application to get ABLC approved for use in Europe. PMID:12345310

  17. Efficient Stem Cell Collection after Modified Cisplatin-Based Mobilization Chemotherapy in Patients with Diffuse Large B Cell Lymphoma.

    PubMed

    Lisenko, Katharina; Cremer, Martin; Schwarzbich, Mark-Alexander; Kriegsmann, Mark; Ho, Anthony D; Witzens-Harig, Mathias; Wuchter, Patrick

    2016-08-01

    In patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL), R-DHAP (rituximab, dexamethasone, cytarabine, and cisplatin) is a commonly used regimen for salvage therapy and for mobilization of peripheral blood stem cells (PBSCs). At our center, a modified R-DHAP regimen with administration of 25 mg/m(2) cisplatin as a 3-hour infusion over 4 consecutive days, instead of a single infusion of 100 mg/m(2) over 24 hours, has been established. The aim of this study was to analyze the efficiency of this modified R-DHAP regimen plus G-CSF as a mobilization strategy. We retrospectively analyzed clinical characteristics, PBSC collection and autologous stem cell transplantation parameters, and hematologic reconstitution data for 65 patients with relapsed or refractory DLBCL who underwent PBSC collection after mobilization with the modified R-DHAP protocol at our institution between 2002 and 2013. Data were evaluated for the overall cohort and with regard to the number of R-DHAP cycles received before PBSC collection. PBSC collection was performed after the first R-DHAP course in 32 patients (49%), after the second course in 30 patients (46%), and after the third course in 3 patients (5%). Sixty-three patients (97%) achieved the collection goal of ≥2.0 × 10(6) CD34(+) cells/kg body weight. A significantly higher median CD34(+) cell collection yield was achieved when cells were collected after the first R-DHAP course compared with after the second course (P < .01). A peripheral blood leukocyte increase of ≥1.0 × 10(9)/L and a platelet increase of ≥20 × 10(9)/L were observed by 11 days after ASCT. In our cohort, the modified R-DHAP regimen proved safe and feasible, showed an overall response rate (complete response, complete response unconfirmed, and partial response) of 66%, and allowed efficient mobilization of CD34(+) cells for PBSC collection. PMID:27060439

  18. R-CVP regimen is active in frail elderly patients aged 80 or over with diffuse large B cell lymphoma.

    PubMed

    Laribi, Kamel; Denizon, Nathalie; Bolle, Delphine; Truong, Catherine; Besançon, Anne; Sandrini, Jeremy; Anghel, Andreaa; Farhi, Jonathan; Ghnaya, Habib; Baugier de Materre, Alix

    2016-10-01

    Patients aged 80 or over with diffuse large B cell lymphoma (DLBCL) often have comorbidities that increase drug toxicity and prevent the use of otherwise optimal treatment. We performed a retrospective analysis of 43 patients aged 80 or over (median age: 83; range: 80-93) unable to receive treatment with anthracyclines, at diagnosis of DLBCL, treated with an R-CVP treatment (standard R-CHOP without doxorubicin). The patients had one or more comorbidities: 18 patients (41.9 %) had a performance status (PS) of 3; 23 patients (53.5 %) had low creatinine clearance; 12 patients (27.9 %) had low left ventricular ejection fraction; seven patients (16.3 %) had poor hepatic function; and 26 patients (60.5 %) had a Charlson index score ≥4. Thirty patients (70 %) had two or three adverse factors according to the age-adjusted International Prognostic Index. Twenty-five patients (58.1 %) received eight cycles of R-CVP, but the full eight cycles could not be given to 18 patients (41.9 %). The OR rate was 58.1 % (CR 37.2 %). There were 34 deaths (79 %) during treatment and follow-up. Ten patients (23.3 %) died early from toxicity before interim evaluation; all had PS 3. The median follow-up of surviving patients was 52.6 months. The overall 2-year survival rate was 31.9 % and the median OS was 12.6 months. The median OS for patients who completed the entire treatment was 26.4 months. The median PFS was 11.2 months. In multivariate analyses, OS was only affected by performance status ≥2 and Charlson index score ≥4. The R-CVP regimen can be active in elderly frail patients aged 80 or more with DLBCL, but systematic geriatric assessment is required so that those unsuitable for chemotherapy are excluded. PMID:27485454

  19. Prognostic significance of bone marrow infiltration detected by PET-CT in newly diagnosed diffuse large B cell lymphoma

    PubMed Central

    Liang, Jin-Hua; Sun, Jin; Wang, Li; Fan, Lei; Chen, Yao-Yu; Qu, Xiao-Yan; Li, Tian-Nv; Li, Jian-Yong; Xu, Wei

    2016-01-01

    The aim of this study was to examine the prognostic value of bone marrow involvement (BMI) assessed by baseline PET-CT (PET(0)-BMI) in treatment-naïve patients with diffuse large B-cell lymphoma (DLBCL). All patients from a single centre diagnosed as DLBCL between 2005 and 2014 had data extracted from staging PET-CT (PET(0)-CT), bone marrow biopsy (BMB), and treatment records. The PET(3)-CT (PET-CT scan after cycle 3 of immunochemotherapy) was performed on all the patients with PET(0)-BMI positivity (PET(0)-BMI(+)). Of 169 patients, 20 (11.8%) had BMI on BMB, whereas 35 (20.7%) were PET(0)-BMI positive. Among PET(0)-BMI(+) patients, patients with maximum of standard uptake value (SUVmax) of bone marrow (SUVmax(BM)) more than 8.6 were significantly associated with high IPI score (3–5) (P=0.002), worse progression-free survival (PFS) and overall survival (OS) (P=0.025 and P=0.002, respectively). In the 68 stage IV cases, 3-year OS was higher in the patients with negative PET(0)-BMI (PET(0)-BMI(−)) than that with PET(0)-BMI(+) (84.2%±6.5% vs. 44.1%±8.6%; P=0.003), while 3-year PFS only shown a trend of statistic significance (P=0.077) between the two groups. Among the 69 patients of inter-risk of IPI (2–3), patients with PET(0)-BMI(+) had significantly inferior PFS and OS than that with PET(0)-BMI(−) (P=0.009 and P<0.001, respectively). The cut-off value of the decreased percentage of SUVmax(BM) between PET(0)-CT and PET(3)-CT (ΔSUVmax(BM)) was 70.0%, which can predict PFS (P=0.003) and OS (P=0.023). These data confirmed that along with the increased sensitivity and accuracy of identifying bone marrow by PET-CT, novel prognostic values of marrow involvement were found in patients with DLBCL. PMID:26919239

  20. Ratios of Four STAT3 Splice Variants in Human Eosinophils and Diffuse Large B Cell Lymphoma Cells

    PubMed Central

    Turton, Keren B.; Annis, Douglas S.; Rui, Lixin; Esnault, Stephane; Mosher, Deane F.

    2015-01-01

    Signal transducer and activator of transcription 3 (STAT3) is a key mediator of leukocyte differentiation and proliferation. The 3' end of STAT3 transcripts is subject to two alternative splicing events. One results in either full-length STAT3α or in STAT3β, which lacks part of the C-terminal transactivation domain. The other is at a tandem donor (5') splice site and results in the codon for Ser-701 being included (S) or excluded (ΔS). Despite the proximity of Ser-701 to the site of activating phosphorylation at Tyr-705, ΔS/S splicing has barely been studied. Sequencing of cDNA from purified eosinophils revealed the presence of four transcripts (S-α, ΔS-α, S-β, and ΔS-β) rather than the three reported in publically available databases from which ΔS-β is missing. To gain insight into regulation of the two alternative splicing events, we developed a quantitative(q) PCR protocol to compare transcript ratios in eosinophils in which STAT3 is upregulated by cytokines, activated B cell diffuse large B cell Lymphoma (DLBCL) cells in which STAT3 is dysregulated, and in germinal center B cell-like DLBCL cells in which it is not. With the exception of one line of activated B cell DLCBL cells, the four variants were found in roughly the same ratios despite differences in total levels of STAT3 transcripts. S-α was the most abundant, followed by S-β. ΔS-α and ΔS-β together comprised 15.6±4.0 % (mean±SD, n=21) of the total. The percentage of STAT3β variants that were ΔS was 1.5-fold greater than of STAT3α variants that were ΔS. Inspection of Illumina’s “BodyMap” RNA-Seq database revealed that the ΔS variant accounts for 10-26 % of STAT3 transcripts across 16 human tissues, with less variation than three other genes with the identical tandem donor splice site sequence. Thus, it seems likely that all cells contain the S-α, ΔS-α, S-β, and ΔS-β variants of STAT3. PMID:25984943

  1. Specificity of anti-lymphocyte antibodies in sera from patients with AIDS-related complex (ARC) and healthy homosexuals.

    PubMed Central

    Warren, R Q; Johnson, E A; Donnelly, R P; Lavia, M F; Tsang, K Y

    1988-01-01

    The presence and specificity of anti-lymphocyte antibodies (ALA) was investigated in sera from male homosexuals with AIDS-Related Complex (ARC) as well as healthy homosexuals. Individuals in the healthy homosexual group had no detectable antibodies to human immunodeficiency virus (HIV). Antibodies reactive with normal peripheral blood mononuclear cells were detected by Western blot analysis in sera from both groups of homosexuals. Of those individuals whose sera contained ALA, 71% of ARC patients and 83% of healthy homosexuals had antibodies recognizing a 73 kilodalton (kD) molecule. ALA present in ARC sera reacted with CD3+, CD4+ and CD8+ lymphocytes while little reactivity with B cells was observed. Our results indicate that ALA appear in homosexuals prior to HIV infection and are reactive primarily with T lymphocytes. A 73 kD structure associated with the T cell membrane is frequently the target for these antibodies. Images Fig. 1 Fig. 2 Fig. 3 PMID:3052941

  2. PHASE II AIDS MALIGNANCY CONSORTIUM TRIAL OF TOPICAL HALOFUGINONE IN AIDS-RELATED KAPOSI’S SARCOMA

    PubMed Central

    Koon, Henry B.; Fingleton, Barbara; Lee, Jeannette Y.; Geyer, Julia T.; Cesarman, Ethel; Parise, Robert A.; Egorin, Merrill J.; Dezube, Bruce J.; Aboulafia, David; Krown, Susan E.

    2010-01-01

    Using a novel blinded intra-patient vehicle control design, we conducted a phase II study of topically-administered halofuginone, an angiogenesis inhibitor that inhibits collagen type-I and matrix metalloproteinases (MMPs), in patients with AIDS-related Kaposi’s sarcoma (KS). Serial KS biopsies assessed treatment effects on angiogenic factors and KSHV-LANA. We observed marked heterogeneity of KSHV-LANA expression. Although the small number of subjects whose response could be evaluated precluded definitive assessment of halofuginone’s efficacy, we observed a significant decrease in type-I collagen only in halofuginone-treated lesions, but no effect on MMP-2. The trial design is applicable to future studies of topical agents. PMID:21068672

  3. Help-seeking for AIDS-related concerns: a comparison of gay men with various HIV diagnoses.

    PubMed

    Hays, R B; Catania, J A; McKusick, L; Coates, T J

    1990-10-01

    Examined help-seeking and psychological distress among four groups of gay men (30 AIDS-diagnosed, 107 HIV-seropositive, 149 HIV-seronegative, 244 untested) in the AIDS Behavioral Research Project, a longitudinal survey of San Francisco gay men. The men reported high levels of anxiety, depression, and help-seeking from their social networks. AIDS-diagnosed and HIV-positives reported the most AIDS worry and were the most likely to seek help. High percentages of AIDS-diagnosed men sought help from all sources (peers, professionals, family), whereas nondiagnosed men were more likely to seek help from peers. Regardless of the men's HIV status, peers were perceived to be the most helpful source. Family members were less likely sought and perceived as least helpful. The strengths and limitations of peers as social support providers for AIDS-related concerns are discussed, including implications for the design of community programs to enhance the abilities of peer helpers. PMID:2075900

  4. Professionalisation and social attitudes: a protocol for measuring changes in HIV/AIDS-related stigma among healthcare students

    PubMed Central

    Ahmadi, Keivan; Reidpath, Daniel D; Allotey, Pascale; Hassali, Mohamed Azmi Ahmad

    2013-01-01

    Introduction HIV/AIDS-related stigma affects the access and utilisation of health services. Although HIV/AIDS-related stigma in the health services has been studied, little work has attended to the relationship between professional development and stigmatising attitudes. Hence, in this study, we will extend earlier research by examining the relationship between the stage of professional development and the kinds of stigmatising attitudes held about people living with HIV/AIDS. Methods and analysis A serial cross-sectional design will be combined with a two-point in time longitudinal design to measure the levels of stigma among healthcare students from each year of undergraduate and graduate courses in Malaysia and Australia. In the absence of suitable measures, we will carry out a sequential mixed methods design to develop such a tool. The questionnaire data will be analysed using mixed effects linear models to manage the repeated measures. Ethics and dissemination We have received ethical approval from the Monash MBBS executive committee as well as the Monash University Human Research Ethics Committee. We will keep the data in a locked filing cabinet in the Monash University (Sunway campus) premises for 5 years, after which the information will be shredded and disposed of in secure bins, and digital recordings will be erased in accordance with Monash University's regulations. Only the principal investigator and the researcher will have access to the filing cabinet. We aim to present and publish the results of this study in national and international conferences and peer-reviewed journals, respectively. PMID:23793653

  5. Altered natural history of AIDS-related opportunistic infections in the era of potent combination antiretroviral therapy.

    PubMed

    Jacobson, M A; French, M

    1998-01-01

    Since potent HIV protease inhibitor drugs became widely available in early 1996, many HIV clinical specialists have noted a marked decrease in the occurrence of AIDS-related opportunistic infections, and some specialists have reported unusual clinical presentations and manifestations of previously common opportunistic infections. In this article, we will review (1) the available data regarding recent trends in AIDS-related opportunistic infections incidence and manifestations, (2) clinical and immunologic evidence that potent combination antiretroviral therapy can alter the natural history of these opportunistic infections, and (3) the implications of these findings for current patient management practice and future clinical and immunologic research. As a preface to this review, however, it is important to acknowledge that any evaluation of the potential benefit of potent combination antiretroviral therapy in reducing the risk of serious opportunistic infections can be confounded by the concomitant use of prophylactic antimicrobial agents co-administered to prevent specific opportunistic infections. For example, it is standard clinical practice to administer trimethoprim-sulfamethoxazole (or another agent if trimethoprim-sulfamethoxazole cannot be tolerated) to patients with an absolute CD4 lymphocyte count < 200 cells/microliters, unexplained chronic fever or a history of oropharyngeal candidiasis. Similarly, specific antimicrobial prophylaxis to prevent disseminated Mycobacterium avium complex (MAC) infection in patients with absolute CD4 counts < 50 cells/microliters is also a widely recommended guideline. Although the relative efficacies of specific antimicrobial prophylaxis regimens in preventing the most common life- and sight-threatening opportunistic infectious complications of AIDS [Pneumocystis carinii pneumonia (PCP), disseminated MAC infection, and cytomegalovirus (CMV) retinitis] are now well established, these relative efficacies were established in

  6. Primary colorectal lymphoma comprising both components of diffuse large B-cell lymphoma and mucosa-associated lymphoid tissue lymphoma combined with cytomegalovirus colitis.

    PubMed

    Katsumata, Ryo; Matsumoto, Hiroshi; Motoyasu, Osawa; Murao, Takahisa; Ishii, Manabu; Fujita, Minoru; Tokunaga, Hirotoshi; Akiyama, Takashi; Wada, Hideho; Sugihara, Takashi; Shiotani, Akiko; Haruma, Ken

    2016-04-01

    A 16-year-old girl presented to our hospital with diarrhea and abdominal pain. The macroscopic findings of colonoscopy revealed multiple submucosal tumors and multiple ulcers, which were localized in the sigmoid colon, and diffuse granular mucosa which extended to the total colon. The pathological diagnosis was malignant lymphoma comprising both components of diffuse large B-cell lymphoma (DLBCL) and mucosa-associated lymphoid tissue (MALT) lymphoma, because the large lymphoma cells were CD20+, CD10-, and CD5-. Furthermore, immunohistochemical analysis of colorectal biopsy samples from multiple ulcers revealed cytomegalovirus (CMV)-positive cells. The patient was diagnosed with primary colorectal lymphoma comprising both components of DLBCL and MALT lymphoma combined with CMV colitis. She received anti-viral medication and chemotherapy. PMID:27015999

  7. The contribution of HGAL/GCET2 in immunohistological algorithms: a comparative study in 424 cases of nodal diffuse large B-cell lymphoma.

    PubMed

    Gualco, Gabriela; Bacchi, Lívia M; Domeny-Duarte, Pollyanna; Natkunam, Yasodha; Bacchi, Carlos E

    2012-11-01

    Diffuse large B-cell lymphoma can be subclassified into at least two molecular subgroups by gene expression profiling: germinal center B-cell like and activated B-cell like diffuse large B-cell lymphoma. Several immunohistological algorithms have been proposed as surrogates to gene expression profiling at the level of protein expression, but their reliability has been an issue of controversy. Furthermore, the proportion of misclassified cases of germinal center B-cell subgroup by immunohistochemistry, in all reported algorithms, is higher compared with germinal center B-cell cases defined by gene expression profiling. We analyzed 424 cases of nodal diffuse large B-cell lymphoma with the panel of markers included in the three previously described algorithms: Hans, Choi, and Tally. To test whether the sensitivity of detecting germinal center B-cell cases could be improved, the germinal center B-cell marker HGAL/GCET2 was also added to all three algorithms. Our results show that the inclusion of HGAL/GCET2 significantly increased the detection of germinal center B-cell cases in all three algorithms (P<0.001). The proportions of germinal center B-cell cases in the original algorithms were 27%, 34%, and 19% for Hans, Choi, and Tally, respectively. In the modified algorithms, with the inclusion of HGAL/GCET2, the frequencies of germinal center B-cell cases were increased to 38%, 48%, and 35%, respectively. Therefore, HGAL/GCET2 protein expression may function as a marker for germinal center B-cell type diffuse large B-cell lymphoma. Consideration should be given to the inclusion of HGAL/GCET2 analysis in algorithms to better predict the cell of origin. These findings bear further validation, from comparison to gene expression profiles and from clinical/therapeutic data. PMID:22743653

  8. 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

    NASA Technical Reports Server (NTRS)

    Pinelli, Thomas E.; Golich, Vicki L.

    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 globalization.

  9. 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

    NASA Technical Reports Server (NTRS)

    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.

  10. The spectrum of B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma: a description of 10 cases.

    PubMed

    Gualco, Gabriela; Natkunam, Yasodha; Bacchi, Carlos E

    2012-05-01

    B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma, is a diagnostic provisional category in the World Health Organization (WHO) 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. Typically, these cases share features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma, or include characteristics of both lymphomas. The rarity of such cases poses a tremendous challenge to both pathologists and oncologists because its differential diagnosis has direct implications for management strategies. In this study, we present 10 cases of B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma and have organized the criteria described by the WHO into four patterns along with detailed clinical, morphological and immunophenotypic characterization and outcome data. Our findings show a male preponderance, median age of 37 years and a mediastinal presentation in 80% of cases. All cases expressed at least two markers associated with B-cell lineage and good response to combination chemotherapy currently employed for non-Hodgkin lymphomas. PMID:22222636

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

    PubMed Central

    Valera, Alexandra; López-Guillermo, Armando; Cardesa-Salzmann, Teresa; Climent, Fina; González-Barca, Eva; Mercadal, Santiago; Espinosa, Íñigo; 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

    2013-01-01

    MYC alterations influence the survival of patients with diffuse large B-cell lymphoma. Most studies have focused on MYC translocations but there is little information regarding the impact of numerical alterations and protein expression. We analyzed the genetic alterations and protein expression of MYC, BCL2, BCL6, and MALT1 in 219 cases of diffuse large B-cell lymphoma. MYC rearrangement occurred as the sole abnormality (MYC single-hit) in 3% of cases, MYC and concurrent BCL2 and/or BCL6 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. PMID:23716551

  12. HIV/AIDS-related stigmatizing and discriminatory attitudes and recent HIV testing among men who have sex with men in Beijing.

    PubMed

    Li, Xuefeng; Lu, Hongyan; Ma, Xiaoyan; Sun, Yanming; He, Xiong; Li, Chunmei; Raymond, H F; McFarland, Willi; Pan, Stephen W; Shao, Yiming; Vermund, Sten H; Xiao, Yan; Ruan, Yuhua; Jia, Yujiang

    2012-04-01

    This study assessed the correlates of recent HIV testing and HIV/AIDS-related stigmatizing and discriminatory attitudes among men who have sex with men (MSM) in Beijing, China. A cross-sectional study probed demographics, sexual and drug use behaviors, HIV testing, and prevention services. Of 500 participants, 39.3% recently received a test for HIV. Recent testing was independently associated with expressing lower levels of HIV/AIDS-related stigmatizing and discriminatory attitudes, more male sex partners, no female sexual partners and knowing HIV status of their last male partner. Expressing lower levels of HIV/AIDS-related stigmatizing and discriminatory attitudes was independently associated with recent testing, younger age, and knowing HIV status of their last male partner. This study revealed that HIV/AIDS-related stigmatizing and discriminatory attitudes were common and inversely associated with recent HIV testing. Low levels of testing highlighted the urgent needs to reduce HIV/AIDS-related stigma and discrimination and expand HIV testing among MSM in Beijing. PMID:22350831

  13. Topotecan Hydrochloride in Treating Children With Meningeal Cancer That Has Not Responded to Previous Treatment

    ClinicalTrials.gov

    2013-02-20

    AIDS-related Diffuse Large Cell Lymphoma; AIDS-related Diffuse Mixed Cell Lymphoma; AIDS-related Diffuse Small Cleaved Cell Lymphoma; AIDS-related Immunoblastic Large Cell Lymphoma; AIDS-related Lymphoblastic Lymphoma; AIDS-related Peripheral/Systemic Lymphoma; AIDS-related Primary CNS Lymphoma; AIDS-related Small Noncleaved Cell Lymphoma; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; HIV-associated Hodgkin Lymphoma; Leptomeningeal Metastases; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Unspecified Childhood Solid Tumor, Protocol Specific

  14. AIDS-related myopathy.

    PubMed

    Sheikh, Rafiq A.; Yasmeen, Shagufta; Munn, Robert; Ruebner, Boris H.; Ellis, William G.

    1999-09-01

    Infection with the human immunodeficiency virus (HIV) is often associated with the acquired immunodeficiency syndrome (AIDS), and wasting is one of the defining clinical features of AIDS. Muscular weakness due to myopathy may develop at any stage of HIV infection. We report two illustrative cases of HIV-associated myopathies. One was due to inflammatory myosits most likely directly related to the HIV infection, and the other was most likely the result of mitochondrial damage due to zidovudine, a nucleoside analogue commonly used in treating HIV infection. Biopsies from both patients showed alterations of myofiber structures, of varying severity, culminating in necrosis, lipid droplets, and lymphoplasmocytic inflammatory response. The zidovudine-treated patient also showed distinctive mitochondrial changes, predominantly enlargement, variation in shape and size, and disorganization of the cristae. These two types of HIV-associated inflammatory myopathies are reviewed, along with other HIV-associated myopathies, including HIV wasting syndrome, nemaline rod myopathy, pyomyositis, rhabdomyolysis, cardiomyopathy, and other miscellaneous myopathies associated with HIV infection. PMID:11810429

  15. A three-dimensional diffusion/convection model of the large scale magnetic field in the Venus ionosphere

    NASA Technical Reports Server (NTRS)

    Luhmann, J. G.

    1988-01-01

    A three-dimensinal diffusion/convection model of the dayside Venus ionosphere magnetic field was developed on the basis of previously published one-dimensional diffusion/convection models, and assuming that the field and flow at the upper boundary (in the magnetic barrier) as well as the ionospheric plasma velocity are known. The results indicate that the low-altitude magnetosheath field draping may be distorted by the interaction with the ionosphere in such a manner that there is an apparent 'focusing' of the field toward the subsolar point, caused by the shear in the horizontal velocity between the magnetosheath and ionospheric flows. A comparison of published magnetic-field observations with the present results indicates that the simple nesting of external and internal velocity fields may be a good approximation to global plasma flows near Venus under normal conditions.

  16. Time Dependent Density Functional Theory Calculations of Large Compact PAH Cations: Implications for the Diffuse Interstellar Bands

    NASA Technical Reports Server (NTRS)

    Weisman, Jennifer L.; Lee, Timothy J.; Salama, Farid; Gordon-Head, Martin; Kwak, Dochan (Technical Monitor)

    2002-01-01

    We investigate the electronic absorption spectra of several maximally pericondensed polycyclic aromatic hydrocarbon radical cations with time dependent density functional theory calculations. We find interesting trends in the vertical excitation energies and oscillator strengths for this series containing pyrene through circumcoronene, the largest species containing more than 50 carbon atoms. We discuss the implications of these new results for the size and structure distribution of the diffuse interstellar band carriers.

  17. Active translocon complexes labeled with GFP-Dad1 diffuse slowly as large polysome arrays in the endoplasmic reticulum.

    PubMed

    Nikonov, Andrei V; Snapp, Erik; Lippincott-Schwartz, Jennifer; Kreibich, Gert

    2002-08-01

    In the ER, the translocon complex (TC) functions in the translocation and cotranslational modification of proteins made on membrane-bound ribosomes. The oligosaccharyltransferase (OST) complex is associated with the TC, and performs the cotranslational N-glycosylation of nascent polypeptide chains. Here we use a GFP-tagged subunit of the OST complex (GFP-Dad1) that rescues the temperature-sensitive (ts) phenotype of tsBN7 cells, where Dad1 is degraded and N-glycosylation is inhibited, to study the lateral mobility of the TC by FRAP. GFP-Dad1 that is functionally incorporated into TCs diffuses extremely slow, exhibiting an effective diffusion constant (Deff) about seven times lower than that of GFP-tagged ER membrane proteins unhindered in their lateral mobility. Termination of protein synthesis significantly increases the lateral mobility of GFP-Dad1 in the ER membranes, but to a level that is still lower than that of free GFP-Dad1. This suggests that GFP-Dad1 as part of the OST remains associated with inactive TCs. Our findings that TCs assembled into membrane-bound polysomes diffuse slowly within the ER have mechanistic implications for the segregation of the ER into smooth and rough domains. PMID:12163472

  18. HIV/AIDS - Related Knowledge, Attitudes, and Sexual Practices among Migrant Wives in Rural Anhui Province, China

    PubMed Central

    Zou, Huachun; Dai, Xin; Meng, Xiaojun; Wang, Huadong; Jiang, Chao; Wang, Yanchun; Zhang, Lin; Gao, Yongqing; Tang, Song; Xu, Tan; Sun, Wenjie; Wen, Yufeng

    2015-01-01

    Background Migrant wives have been increasing in some poor rural regions of China and they may bridge HIV transmission across regions. This study aimed to assess HIV/AIDS-related knowledge, attitudes and sexual practices among this population in rural Anhui Province, China. Methods A cross-sectional survey was conducted with questionnaire of HIV/AIDS-related knowledge, attitudes, and sexual practices between June 2011 and May 2012. A total of 730 migrant wives and 207 local women were enrolled in this study. Unpaired T-test, Chi-square was utilized to compare the difference of HIV/AIDS knowledge, attitudes and sexual practices between migrant wives and local women. Results Around 80% of the migrant wives were from Yunnan, Guizhou, or Sichuan Provinces. The main sources of HIV/AIDS information were TV/radio, posters, and newspapers/periodicals. HIV/AIDS knowledge level among migrant wives was significantly lower than that among local women (e.g. 47.1% vs 57.0% (p<0.001) answered “Yes” for the question “Can an apparently healthy person be HIV-infected?”), and stigma and prejudice towards HIV/AIDS among migrant wives were more common than those among local women (e.g. 73.2% vs 65.7% (p=0.006) answered “No” for the question “If a shopkeeper or food seller had the HIV, would you buy food from them?”). Compared to local women, migrant wives were more likely to have ever had sex during menstruation (6.8% vs 3.4%, p=0.065) and extramarital sex (17.5% vs 10.1%, p=0.01), and were less likely to consistently use condoms with their husbands (45.8% vs 57.5%, p<0.001) or extramarital sex partners (48.8% vs 58.95, p<0.001). Conclusions Migrant wives in rural China had a low HIV/AIDS knowledge level and high prevalence of stigma and prejudice and risky sexual behaviors. Local HIV/AIDS prevention programs should target this neglected population. PMID:25844269

  19. Toxoplasma gondii Infection in Kyrgyzstan: Seroprevalence, Risk Factor Analysis, and Estimate of Congenital and AIDS-Related Toxoplasmosis

    PubMed Central

    Bodosheva, Aigerim; Kuttubaev, Omurbek; Hehl, Adrian B.; Tanner, Isabelle; Ziadinov, Iskender; Torgerson, Paul R.; Deplazes, Peter

    2013-01-01

    Background HIV-prevalence, as well as incidence of zoonotic parasitic diseases like cystic echinococcosis, has increased in the Kyrgyz Republic due to fundamental socio-economic changes after the breakdown of the Soviet Union. The possible impact on morbidity and mortality caused by Toxoplasma gondii infection in congenital toxoplasmosis or as an opportunistic infection in the emerging AIDS pandemic has not been reported from Kyrgyzstan. Methodology/Principal Findings We screened 1,061 rural and 899 urban people to determine the seroprevalence of T. gondii infection in 2 representative but epidemiologically distinct populations in Kyrgyzstan. The rural population was from a typical agricultural district where sheep husbandry is a major occupation. The urban population was selected in collaboration with several diagnostic laboratories in Bishkek, the largest city in Kyrgyzstan. We designed a questionnaire that was used on all rural subjects so a risk-factor analysis could be undertaken. The samples from the urban population were anonymous and only data with regard to age and gender was available. Estimates of putative cases of congenital and AIDS-related toxoplasmosis in the whole country were made from the results of the serology. Specific antibodies (IgG) against Triton X-100 extracted antigens of T. gondii tachyzoites from in vitro cultures were determined by ELISA. Overall seroprevalence of infection with T. gondii in people living in rural vs. urban areas was 6.2% (95%CI: 4.8–7.8) (adjusted seroprevalence based on census figures 5.1%, 95% CI 3.9–6.5), and 19.0% (95%CI: 16.5–21.7) (adjusted 16.4%, 95% CI 14.1–19.3), respectively, without significant gender-specific differences. The seroprevalence increased with age. Independently low social status increased the risk of Toxoplasma seropositivity while increasing numbers of sheep owned decreased the risk of seropositivity. Water supply, consumption of unpasteurized milk products or undercooked meat, as

  20. Vaneless diffusers

    NASA Astrophysics Data System (ADS)

    Senoo, Y.

    The influence of vaneless diffusers on flow in centrifugal compressors, particularly on surge, is discussed. A vaneless diffuser can demonstrate stable operation in a wide flow range only if it is installed with a backward leaning blade impeller. The circumferential distortion of flow in the impeller disappears quickly in the vaneless diffuser. The axial distortion of flow at the diffuser inlet does not decay easily. In large specific speed compressors, flow out of the impeller is distorted axially. Pressure recovery of diffusers at distorted inlet flow is considerably improved by half guide vanes. The best height of the vanes is a little 1/2 diffuser width. In small specific speed compressors, flow out of the impeller is not much distorted and pressure recovery can be predicted with one-dimensional flow analysis. Wall friction loss is significant in narrow diffusers. The large pressure drop at a small flow rate can cause the positive gradient of the pressure-flow rate characteristic curve, which may cause surging.

  1. Large structure rearrangement of colicin ia channel domain after membrane binding from 2D 13C spin diffusion NMR.

    PubMed

    Luo, Wenbin; Yao, Xiaolan; Hong, Mei

    2005-05-01

    One of the main mechanisms of membrane protein folding is by spontaneous insertion into the lipid bilayer from the aqueous environment. The bacterial toxin, colicin Ia, is one such protein. To shed light on the conformational changes involved in this dramatic transfer from the polar to the hydrophobic milieu, we carried out 2D magic-angle spinning (13)C NMR experiments on the water-soluble and membrane-bound states of the channel-forming domain of colicin Ia. Proton-driven (13)C spin diffusion spectra of selectively (13)C-labeled protein show unequivocal attenuation of cross-peaks after membrane binding. This attenuation can be assigned to distance increases but not reduction of the diffusion coefficient. Analysis of the statistics of the interhelical and intrahelical (13)C-(13)C distances in the soluble protein structure indicates that the observed cross-peak reduction is well correlated with a high percentage of short interhelical contacts in the soluble protein. This suggests that colicin Ia channel domain becomes open and extended upon membrane binding, thus lengthening interhelical distances. In comparison, cross-peaks with similar intensities between the two states are dominated by intrahelical contacts in the soluble state. This suggests that the membrane-bound structure of colicin Ia channel domain may be described as a "molten globule", in which the helical secondary structure is retained while the tertiary structure is unfolded. This study demonstrates that (13)C spin diffusion NMR is a valuable tool for obtaining qualitative long-range distance constraints on membrane protein folding. PMID:15853348

  2. Diffuse Deformation Across the Southern Mariana Margin: Possible Effects of Water on Large-Scale Lithospheric Rheology

    NASA Astrophysics Data System (ADS)

    Martinez, F.; Sleeper, J. D.

    2012-12-01

    The southern Mariana margin is extending in an approximately E-W direction at about 45 mm/yr above the subducting Pacific slab. We use earthquake locations, shallow- and new deep-towed side-scan sonar imagery together with compiled multibeam bathymetry to document the nature of the tectonic and volcanic deformation. A well-defined and magmatically robust spreading center takes up part of this extension along the northern part of the southern margin. However, it does not intersect the trench. Instead the spreading center curves westward and becomes a diffuse zone of volcanism extending to the western end of the back-arc basin. The approximately E-W oriented fabric of this diffuse volcanic zone suggest it is taking up a southerly-directed extensional component associated with southward trench rollback in this area. The main E-W oriented extension in the southern margin appears to be distributed broadly across the margin to the south, as indicated by ~N-S-oriented seafloor fabric and the distribution of earthquakes in this area. Near the outer margin, deep-towed side-scan sonar data to near the 6000 m isobath image possible isolated volcanic emplacements within an otherwise tectonized terrain. Possible ~E-W oriented mullion structures are also imaged suggesting low angle tectonic deformation within the margin. The transition of the organized spreading center to a diffuse volcano-tectonic zone and the broadly distributed deformation in the entire southern margin may be consequences of the high water content in the mantle wedge and overlying lithosphere predicted here. Hydrous and therefore weak subduction margin lithosphere may not be able to localize the narrow plate boundary zones characteristic of extension in oceanic lithosphere.

  3. HIV/AIDS-related knowledge and behaviors among rural married migrant women in Shandong Province, China: a comparison study.

    PubMed

    Song, Yapei; Kang, Dianmin; Wang, Guoyong; Wei, Chongyi; Tao, Xiaorun; Huang, Tao; Qian, Yuesheng; Zhu, Tiwen; Yang, Shan; Yu, Shaoqi; Wang, Hong; Ma, Wei

    2015-02-01

    Migrant women in China are disproportionately affected by HIV/AIDS. This study described HIV/AIDS-related knowledge and behaviors among married migrant women in Shandong province in comparison to non-migrant local women and identified factors associated with HIV testing history and extramarital sex among married migrant women. A probability-based sample of 1,076 migrant and 1,195 local women were included in the analyses. Compared to local women, married migrant women had lower levels of HIV/AIDS knowledge and were more likely to have had premarital sex, extramarital sex, history of sexually transmitted diseases, and drug use. Less than a quarter of migrant women used condoms consistently in extramarital sex. Only 31.0 % of married migrant women had ever tested for HIV, and the rate of premarital HIV testing was very low. Multivariable analysis showed that married migrant women with a history of extramarital sex were more likely to be from Yunnan province, be living in Yantai city, be in their first marriage, have lower family income, have poor relationship with spouses, use drug, have a history of sexually transmitted diseases, and have lower social support. Our findings provide further evidence that married migrant women are at higher risk for HIV infection and that targeted interventions need to be developed for this population. PMID:25323941

  4. Possibility of formation of a disoriented chiral condensate in p p collisions at energies available at the CERN Large Hadron Collider via the reaction-diffusion equation

    NASA Astrophysics Data System (ADS)

    Bagchi, Partha; Das, Arpan; Sengupta, Srikumar; Srivastava, Ajit M.

    2016-02-01

    There are indications of formation of a thermalized medium in high multiplicity p p collisions at energies available at the CERN Large Hadron Collider. It is possible that such a medium may reach high enough energy density and temperature that a transient stage of quark-gluon plasma, where chiral symmetry is restored, may be achieved. Due to rapid three-dimensional expansion, the system will quickly cool, undergoing a spontaneous chiral symmetry breaking transition. We study the dynamics of the chiral field, after the symmetry breaking transition, for such an event using a reaction-diffusion equation approach which we have recently applied for studying QCD transitions in relativistic heavy-ion collisions. We show that the interior of such a rapidly expanding system is likely to lead to the formation of a single large domain of disoriented chiral condensate (DCC), which has been a subject of intensive search in earlier experiments. We argue that large multiplicity p p collisions naturally give rise to required boundary conditions for the existence of slowly propagating front solutions of the reaction-diffusion equation with resulting dynamics of the chiral field leading to the formation of a large DCC domain.

  5. Effect of local velocity on diffusion-induced stress in large-deformation electrodes of lithium-ion batteries

    NASA Astrophysics Data System (ADS)

    Li, Yong; Zhang, Kai; Zheng, Bailin; Yang, Fuqian

    2016-07-01

    In this work, the contribution of local velocity to the resultant flux of lithium in lithium-ion battery is introduced into the diffusion equation to describe the migration of lithium in the active material of electrodes. The effect of the local velocity on the stress evolution in a spherical electrode made of silicon is analyzed, using the derived diffusion equation and nonlinear theory of elasticity. Two boundary conditions at the surface of the electrode, which represent two extreme conditions of real electrode materials, are used in the stress analysis: one is stress-free, and the other is immobile. The numerical results with the stress-free boundary condition suggest that the effect of the local velocity on the distribution of radial stress and hoop stress increases with the increase of time and the effect of the local velocity on the distribution of lithium is relatively small. In comparison with the results without the effect of the local velocity, the effect of the local velocity is negligible for the immobile boundary condition. The numerical result shows that the use of the immobile boundary condition leads to the decrease of von-Mises stress, which likely will retard the mechanical degradation of electrode and improve the electrochemical performance of lithium-ion battery.

  6. Diffuse fatty metamorphosis of a large, well-differentiated hepatocellular carcinoma originating in the normal liver: a case report and literature review.

    PubMed

    Komiyama, Satoshi; Okazaki, Hiroshi; Nakao, Satoshi; Nishigori, Shuhei; Terada, Masahiro; Hamanaka, Jun; Miura, Yuki; Oka, Hiroyuki; Suzaki, Fumio; Tanaka, Katsuaki

    2015-10-01

    Fatty changes are frequently observed in small, well-differentiated hepatocellular carcinomas (HCCs), but are rarely observed in large (over 30 mm in diameter) lesions. Here, we report a 76-year-old man who developed a large (58 mm in diameter), well-differentiated HCC with diffuse extensive fatty changes in the right lobe of the liver. He had no history of alcohol abuse, obesity, or hepatitis B or C infection, and no autoantibodies, but he did have type 2 diabetes. The serum alpha-fetoprotein level was within the normal range, and ultrasonography showed a round hyperechoic lesion. Dynamic contrast-enhanced computed tomography revealed a tumor with inhomogeneous low attenuation in the arterial, portal, and venous phases, mimicking an angiomyolipoma. The patient underwent central bisegmentectomy of the liver, and the histological diagnosis was well-differentiated HCC with diffuse extensive fatty changes. The surrounding non-cancerous area was normal. A review of the published literature found six published cases of large, well-differentiated HCC with extensive fatty changes. Unlike the patients in most previous reports, our patient did not have any underlying liver disease and had no history of alcohol abuse. PMID:26416601

  7. B cell lymphoma, unclassifiable, with features intermediate between diffuse large B cell lymphoma and classical hodgkin lymphoma: diagnosis by fine-needle aspiration cytology.

    PubMed

    Lynnhtun, Kyaw; Varikatt, Winny; Pathmanathan, Nirmala

    2014-08-01

    A 58-year-old lady presented with mediastinal lymphadenopathy. A thoracoscopic ultrasound-guided fine-needle aspiration showed large atypical epithelioid cells arranged in cohesive sheets and dispersed as single cells with intact cytoplasm amid a background of lymphocytes and histiocytes. A cytological diagnosis of "a malignant neoplasm" was made, raising a broad list of differential diagnoses. A broad panel of immunocytochemical stains performed on the cell block was indicative of a lymphoproliferative disorder, but the immunophenotype was intermediate between diffuse large B cell lymphoma (DLBCL) and classical Hodgkin lymphoma (cHL). Diffuse and strong reactivity to CD20, CD79a, and PAX-5, and weak reactivity to CD30, was in favor of a DLBCL, or more precisely mediastinal (thymic) large B cell lymphoma (MLBL). However, there were negative staining for LCA, OCT-2, and BOB-1 as well as positive staining for EBV-encoded RNA, which were against a diagnosis of MLBL and raised the possibility of cHL. The absence of RS cells and the typical mileu, the negativity for CD15 and the strong positivity of CD20 and PAX-5 were against a diagnosis of cHL. On this basis, the diagnosis of "B-cell lymphoproliferative disorder with features intermediate between DLBCL and cHL" was rendered. The diagnosis was subsequently confirmed on excisional biopsy. This case report demonstrates broad differential diagnoses raised by this diagnostic entity and the importance of an adequate cell block for accurate designation. PMID:23630122

  8. Rituximab in combination with platinum-containing chemotherapy in patients with relapsed or primary refractory diffuse large B-cell lymphoma.

    PubMed

    Bieker, Ralf; Kessler, Torsten; Berdel, Wolfgang E; Mesters, Rolf M

    2003-01-01

    The aim of the study was to evaluate the efficacy of a regimen consisting of rituximab and a platinum-containing chemotherapy with either Ifosfamide, Carboplatin and Etoposide (ICE) or Cisplatin, high-dose Ara-C and Dexamethasone (DHAP) in patients with relapsed or primary refractory diffuse large B-cell lymphoma. Ten patients with relapsed or primary refractory diffuse large B-cell lymphoma were treated from June 2000 until May 2001 with a platinum-containing chemotherapy regimen according to the ICE- or DHAP-protocol in combination with rituximab at the University of Muenster. Two cycles of ICE or DHAP and rituximab were given. In case of at least a minor response after 2 cycles, 2 additional cycles of the same combination were applied. Response rate, remission duration and duration of survival were evaluated. All 10 patients could be analysed with respect to these endpoints. No treatment related mortality was observed. The response rate (CR/PR) was 60% (10/50%). Twenty percent of the patients had progressive disease. The median duration of remission and survival was 3 and 3.5 months, respectively (range: 1-6 and 1-7 months, respectively), the survival rate was 10%. Eight of 10 patients died because of their underlying disease with short remission duration, 1 patient died of complications of allogeneic transplantation in CR. In conclusion, the combination of platinum-containing chemotherapy (ICE or DHAP) with rituximab demonstrates significant activity in intensively pretreated patients with relapsed or primary refractory diffuse large B-cell lymphoma. Considering the short duration of remission and survival, respectively, other experimental therapeutic approaches (e.g. allogeneic stem cell transplantation, radioimmunotherapy) should be pursued following this treatment in order to induce long-term remission. PMID:14534718

  9. Genome-wide profiling identifies a DNA methylation signature that associates with TET2 mutations in diffuse large B-cell lymphoma.

    PubMed

    Asmar, Fazila; Punj, Vasu; Christensen, Jesper; Pedersen, Marianne T; Pedersen, Anja; Nielsen, Anders B; Hother, Christoffer; Ralfkiaer, Ulrik; Brown, Peter; Ralfkiaer, Elisabeth; Helin, Kristian; Grønbæk, Kirsten

    2013-12-01

    The discovery that the Ten-Eleven Translocation (TET) hydroxylases cause DNA demethylation has fundamentally changed the notion of how DNA methylation is regulated. Clonal analysis of the hematopoetic stem cell compartment suggests that TET2 mutations can be early events in hematologic cancers and recent investigations have shown TET2 mutations in diffuse large B-cell lymphoma. However, the detection rates and the types of TET2 mutations vary, and the relation to global methylation patterns has not been investigated. Here, we show TET2 mutations in 12 of 100 diffuse large B-cell lymphomas with 7% carrying loss-of-function and 5% carrying missense mutations. Genome-wide methylation profiling using 450K Illumina arrays identified 315 differentially methylated genes between TET2 mutated and TET2 wild-type cases. TET2 mutations are primarily associated with hypermethylation within CpG islands (70%; P<0.0001), and at CpG-rich promoters (60%; P<0.0001) of genes involved in hematopoietic differentiation and cellular development. Hypermethylated loci in TET2 mutated samples overlap with the bivalent (H3K27me3/H3K4me3) silencing mark in human embryonic stem cells (P=1.5×10(-30)). Surprisingly, gene expression profiling showed that only 11% of the hypermethylated genes were down-regulated, among which there were several genes previously suggested to be tumor suppressors. A meta-analysis suggested that the 35 hypermethylated and down-regulated genes are associated with the activated B-cell-like type of diffuse large B-cell lymphoma in other studies. In conclusion, our data suggest that TET2 mutations may cause aberrant methylation mainly of genes involved in hematopoietic development, which are silenced but poised for activation in human embryonic stem cells. PMID:23831920

  10. Survival impact of rituximab combined with ACVBP and upfront consolidation autotransplantation in high-risk diffuse large B-cell lymphoma for GELA

    PubMed Central

    Fitoussi, Olivier; Belhadj, Karim; Mounier, Nicolas; Parrens, Marie; Tilly, Hervé; Salles, Gilles; Feugier, Pierre; Ferme, Christophe; Ysebaert, Loic; Gabarre, Jean; Herbrecht, Raoul; Janvier, Maud; Van Den Neste, Eric; Morschhauser, Franck; Casasnovas, Olivier; Ghesquieres, Hervé; Anglaret, Bruno; Brechignac, Sabine; Haioun, Corinne; Gisselbrecht, Christian

    2011-01-01

    Background As rituximab combined with CHOP improves complete remission and overall survival in diffuse large B-cell lymphoma, intensified chemotherapy followed by autologous stem-cell transplantation has also been advocated for high-risk patients. The aim of this study was to establish whether or not combining rituximab with high-dose chemotherapy and auto-transplantation also benefits patient survival. Design and Methods The LNH2003-3 study was a phase II trial including diffuse large B-cell lymphoma patients with 2 or 3 International Prognostic Index factors. They received four cycles of intensive biweekly chemotherapy with rituximab, doxorubicine, cyclophosphamide, vindesine, bleomycine, prednisolone (R-ACVBP) followed by auto-transplantation in responding patients. Two hundred and nine patients under 60 years of age were included in the study and 155 responding patients underwent auto-transplantation. In addition, a case-control study was performed by matching (1:1) 181 patients treated with R-ACVBP with ACVBP patients not given rituximab but submitted to auto-transplantation from the previous LNH1998-3 trial. Results With a median follow up of 45 months, 4-year progression-free survival and overall survival were estimated at 76% (CI: 69–81) and 78% (CI: 72–83), respectively. There was no difference between patients with 2 or 3 International Prognostic Index factors. Four year progression-free survival was significantly higher in R-ACVBP than ACVBP patients (74% vs. 58%; P=0.0005). There was also a significant increase in 4-year overall survival (76% vs. 68%; P=0.0494). Conclusions In high-risk diffuse large B-cell lymphoma patients, treatment with R-ACVBP followed by auto-transplantation results in a 78% 4-year overall survival which should be compared to other approaches. (Clinicaltrials.gov identifier: NCT00144807) PMID:21546499

  11. Longitudinal Effects of Coping on Outcome in a Randomized Controlled Trial of a Group Intervention for HIV-Positive Adults with AIDS-Related Bereavement

    ERIC Educational Resources Information Center

    Hansen, Nathan B.; Tarakeshwar, Nalini; Ghebremichael, Musie; Zhang, Heping; Kochman, Arlene; Sikkema, Kathleen J.

    2006-01-01

    This study examined the longitudinal effects of coping on outcome one year following completion of a randomized, controlled trial of a group coping intervention for AIDS-related bereavement. Bereaved HIV-positive participants (N = 267) were administered measures of grief, psychiatric distress, quality of life, and coping at baseline,…

  12. With and With"out": The Bereavement Experiences of Gay Men Who Have Lost a Partner to Non-AIDS-Related Causes

    ERIC Educational Resources Information Center

    Hornjatkevyc, Nina L.; Alderson, Kevin G.

    2011-01-01

    This study gives voice to the experiences of gay men who have lost a partner to non-AIDS-related causes, a subject that has received little attention in the psychological literature. Interviews were conducted with 8 gay men. An analysis informed by hermeneutic phenomenology generated themes and contextualized meanings regarding the participants'…

  13. The Unfinished Nature of Rights-Informed HIV- and AIDS-Related Education: An Analysis of Three School-Based Initiatives

    ERIC Educational Resources Information Center

    Miedema, Esther; Maxwell, Claire; Aggleton, Peter

    2015-01-01

    Over the past 25 years, there has been growing investment in concepts of rights in the areas of HIV prevention, care and treatment, including HIV- and AIDS-related education delivered in schools. Despite this increasing commitment to the notion of rights, few efforts appear to have been made to understand the varying conceptions of rights that…

  14. A rare case of the upper extremity diffuse large B-cell lymphoma mimicking soft tissue sarcoma in an elderly patient

    PubMed Central

    Mamorska-Dyga, Aleksandra; Ronny, Faisal M. H.; Puccio, Carmelo; Islam, Humayun

    2016-01-01

    Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, with about 30% of new cases presenting with extranodal disease. Lesions originating from soft tissues of the upper extremities are extremely rare and may mimic other malignancies like sarcoma. We present a case of an elderly patient with right upper extremity (RUE) mass which was proven to be DLBCL instead of sarcoma. We emphasize the increasing need for investigating new therapeutic options for patients of extreme age and/or with underlying heart disease. PMID:27486587

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

    Cancer.gov

    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.

  16. Autograft HIV-DNA Load Predicts HIV-1 Peripheral Reservoir After Stem Cell Transplantation for AIDS-Related Lymphoma Patients

    PubMed Central

    Bortolin, Maria Teresa; Pratesi, Chiara; Tedeschi, Rosamaria; Basaglia, Giancarlo; Abbruzzese, Luciano; Mazzucato, Mario; Spina, Michele; Vaccher, Emanuela; Tirelli, Umberto; Rupolo, Maurizio; Michieli, Mariagrazia; Di Mascio, Michele; De Paoli, Paolo

    2015-01-01

    Abstract Autologous stem cell transplantation (ASCT) is a widely used procedure for AIDS-related lymphomas, and it represents an opportunity to evaluate strategies curing HIV-1 infection. The association of autograft HIV-DNA load with peripheral blood HIV-1 reservoir before ASCT and its contribution in predicting HIV-1 reservoir size and stability during combination antiretroviral therapy (cART) after transplantation are unknown. Aiming to obtain information suggesting new functional cure strategies by ASCT, we retrospectively evaluated HIV-DNA load in autograft and in peripheral blood before and after transplantation in 13 cART-treated HIV-1 relapse/refractoring lymphoma patients. Among them seven discontinued cART after autograft infusion. HIV-DNA was evaluated by a sensitive quantitative real-time polymerase chain reaction (PCR). After debulking chemotherapy/mobilization, the autograft HIV-1 reservoir was higher than and not associated with the peripheral HIV-1 reservoir at baseline [median 215 HIV-DNA copies/106 autograft mononuclear cells, range 13–706 vs. 82 HIV-DNA copies/106 peripheral blood mononuclear cells (PBMCs), range 13–479, p=0.03]. After high dose chemotherapy and autograft infusion, HIV-DNA levels reached a plateau between month 6 and 12 of follow-up. No association was found between peripheral HIV-DNA levels at baseline and after infusion in both cART interrupting and not interrupting patients. Only in the last subgroup, a stable significant linear association between autograft and peripheral blood HIV-1 reservoir emerged from month 1 (R2=0.84, p=0.01) to month 12 follow-up (R2=0.99, p=0.0005). In summary, autograft HIV-1 reservoir size could be influenced by the mobilization phase and predicts posttransplant peripheral HIV-1 reservoir size in patients on continuous cART. These findings could promote new research on strategies reducing the HIV-1 reservoir by using the ASCT procedure. PMID:25581618

  17. Risk factors for HIV infection in male sexual contacts of men with AIDS or an AIDS-related condition.

    PubMed

    Coates, R A; Calzavara, L M; Read, S E; Fanning, M M; Shepherd, F A; Klein, M H; Johnson, J K; Soskolne, C L

    1988-10-01

    A total of 246 healthy male sexual contacts of men with either acquired immunodeficiency syndrome (AIDS) or an AIDS-related condition were recruited into a prospective study in Toronto, Canada between July 1984 and July 1985. At induction, data were collected on the sexual relationship between the contact and his primary case, sexual activities with other men, history of sexually transmitted diseases and other diseases, and use of recreational drugs. At recruitment, 144 sexual contacts had antibodies to human immunodeficiency virus (HIV); 102 of the contacts were seronegative at induction and at three months following recruitment. No association between HIV seropositivity and total number of sexual partners could be demonstrated. In univariate and multivariate analyses, receptive and insertive anal intercourse with the primary cases, and activities which either indicated or potentially caused anorectal mucosal injury (rectal douching, perianal bleeding, receipt of objects in ano, and receptive fisting) were strongly associated with HIV seropositivity. In the final multiple logistic regression model, two significant interaction effects were observed: the interaction between receptive anal intercourse and insertive anal intercourse and that between receptive anal intercourse and the anorectal mucosal injury index. These two interaction terms had negative regression coefficients which suggested that change in one sexual activity would not decrementally reduce risk of HIV infection without a comparable modification in the other activity. No association could be demonstrated between oral-genital and oral-anal sexual contact and odds ratios for these sexual activities declined to levels below 1.0 when adjusted for frequency of receptive anal intercourse. PMID:3421239

  18. Fulminant inflammatory leukoencephalopathy associated with HAART-induced immune restoration in AIDS-related progressive multifocal leukoencephalopathy.

    PubMed

    Vendrely, Aurélie; Bienvenu, Boris; Gasnault, Jacques; Thiebault, Jean Baptiste; Salmon, Dominique; Gray, Françoise

    2005-04-01

    HAART-induced immune restoration is beneficial for patients with AIDS-related progressive multifocal leukoencephalopathy (PML). However, in rare instances, an immune-reconstitution inflammatory syndrome (IRIS) may cause paradoxical clinical deterioration. We report the neuropathological study of an AIDS patient who presented with progressive cognitive deterioration; CD4(+) count was 117 and the HIV viral load >10(4); imaging showed non-enhancing lesions consistent with PML. Following initiation of HAART, CD4(+) was 300 and HIV viral load <10(3), but his neurological symptoms continued to deteriorate. Imaging revealed an increase in the size and number of lesions and enhancement of all the lesions. A stereotactic biopsy showed severe inflammatory and demyelinating lesions with marked infiltration by macrophages and T lymphocytes in the absence of a detectable infectious agent. Despite high doses of steroids, the patient died 3 months after admission. Autopsy showed two types of lesions: (1) active inflammatory PML changes with abundant JC virus, and intraparenchymal and perivascular infiltration by T lymphocytes, and (2) acute perivenous leukoencephalitis devoid of JC virus. Most lymphocytes were CD8(+) lymphocytes; CD4(+) lymphocytes were virtually absent. Two pathological reactions were associated with the paradoxical clinical deterioration related to dysregulation of the immune response characteristic of IRIS in PML: (1) an accentuation of JCV infection, and (2) a nonspecific acute perivenous leukoencephalitis. We suggest that both these types of lesions are due to an imbalance of CD8(+)/CD4(+) T cells, with massive infiltration of the cerebral parenchyma by CD8(+) cytotoxic T lymphocytes in the absence of sufficient CD4(+) response. Better understanding of the mechanisms of the IRIS may enable prevention or cure of this severe, sometimes fatal complication of HAART. PMID:15739098

  19. Thinking outside the halo: tracing the large-scale distribution of diffuse cosmic metals with semi-analytic models

    NASA Astrophysics Data System (ADS)

    Shattow, Genevieve M.; Croton, Darren J.; Bibiano, Antonio

    2015-07-01

    With the installation of the Cosmic Origins Spectrograph on the Hubble Space Telescope, measurements of the metal content of the low-redshift intergalactic medium (IGM) are now available. Using a new grid-based model for diffuse gas coupled to the SAGE semi-analytic model of galaxy formation, we examine the impact of supernova feedback on the pollution of the IGM. We consider different assumptions for the reheating and ejection of gas by supernovae and their dependence on galaxy circular velocity and gas surface density. Where metals are present, we find the most likely metallicity to be -1.5

  20. Role of large-scale slip in mode II fracture of bimaterial interface produced by diffusion bonding

    NASA Astrophysics Data System (ADS)

    Fox, M. R.; Ghosh, A. K.

    2001-08-01

    Bimaterial interfaces present in diffusion-bonded (and in-situ) composites are often not flat interfaces. The unevenness of the interface can result not only from interface reaction products but also from long-range waviness associated with the surfaces of the component phases bonded together. Experimental studies aimed at determining interface mechanical properties generally ignore the departure in the local stress due to waviness and assume a theoretically flat interface. Furthermore, the commonly used testing methods involving superimposed tension often renders the interface so extremely brittle that if microplastic effects were present it becomes impossible to perceive them. This article examines the role of waviness of the interface and microplastic effects on crack initiation. To do this, a test was selected that provides significant stability against crack growth by superimposing compressive stresses. Mode II interface fracture was studied for NiAl/Mo model laminates using a recently developed asymmetrically loaded shear (ALS) interface shear test. The ALS test may be viewed as opposite of the laminate bend test. In the bend test, shear at the interface is created via tension on one surface of the bend, while in the ALS test, shear is created by compression on one side of the interface relative to the other. Normal to the interface, near the crack tip, an initially compressive state is replaced by slight tension due to Poisson’s expansion of the unbonded part of the compressed beam.

  1. Large format cylindrical lens films formed by roll-to-roll ultraviolet embossing and applications as diffusion films

    NASA Astrophysics Data System (ADS)

    Shan, X. C.; Liu, T.; Mohaime, M.; Salam, B.; Liu, Y. C.

    2015-03-01

    A roll-to-roll (R2R) ultraviolet (UV) embossing system has been developed for manufacturing micro features on continuous flexible films. The R2R UV embossing system, which has an embossing roller of 160 mm in diameter, can handle flexible polymer films with a width up to 500 mm and thickness ranging from 0.05 to 0.5 mm. A metal sheet template with micro features on its surface is mounted to the embossing roller and used as embossing mould. A slot die coating unit that has a coating width of 250 mm is used to deposit liquid UV curable resin on polymer films and coating thickness ranging from 10 to 50 µm has been achieved. Continuous roll-to-roll UV embossing is conducted and optical films with cylindrical lens arrays (curvature radius = 112  ±  2 µm, sag height = 28  ±  0.5 µm and pitch = 150  ±  2 µm) are formed. The optical films are used for diffusion to improve light uniformity of a printed lighting film that consists of lighting stripes and dark blank lines. The evaluation results show that the non-uniformity of light intensity can be reduced from 30% (with only lighting panel) to about 3% with the cylindrical lens films.

  2. A Rare Case of Diffuse Large B-cell Lymphoma in a Patient with IgG4-Related Autoimmune Pancreatitis.

    PubMed

    Nishimura, Yoshito; Iwamuro, Masaya; Ocho, Kazuki; Hasegawa, Kou; Kimura, Kosuke; Hanayama, Yoshihisa; Kondo, Eisei; Tanaka, Takehiro; Otsuka, Fumio

    2016-08-01

    A 61-year-old Japanese man with IgG4-related autoimmune pancreatitis was referred to our hospital because of perspiration during food intake. Abdominal computed tomography (CT) with contrast media revealed multiple mesenteric lymphadenopathies. An open surgical abdominal biopsy and subsequent histopathological analysis revealed abnormally large lymphoid cells that were negative for CD3, CD5, and c-myc and positive for CD20 and bcl-2, leading to a diagnosis of diffuse large B-cell lymphoma. Here, we discuss the risk of malignancies, particularly malignant lymphoma in patients with IgG4-related disease. The importance of pathological analysis to reach the appropriate diagnosis in such cases should be emphasized. PMID:27549673

  3. Integrative Analysis Reveals an Outcome-associated and Targetable Pattern of p53 and Cell Cycle Deregulation in Diffuse Large B-cell Lymphoma

    PubMed Central

    Monti, Stefano; Chapuy, Bjoern; Takeyama, Kunihiko; Rodig, Scott J; Hao, Yangsheng; Yeda, Kelly T.; Inguilizian, Haig; Mermel, Craig; Curie, Treeve; Dogan, Ahmed; Kutok, Jeffery L; Beroukim, Rameen; Neuberg, Donna; Habermann, Thomas; Getz, Gad; Kung, Andrew L; Golub, Todd R; Shipp, Margaret A

    2013-01-01

    Summary Diffuse large B-cell lymphoma (DLBCL) is a clinically and biologically heterogeneous disease with a high proliferation rate. By integrating copy number data with transcriptional profiles and performing pathway analysis in primary DLBCLs, we identified a comprehensive set of copy number alterations (CNAs) that decreased p53 activity and perturbed cell cycle regulation. Primary tumors either had multiple complementary alterations of p53 and cell cycle components or largely lacked these lesions. DLBCLs with p53 and cell cycle pathway CNAs had decreased abundance of p53 target transcripts and increased expression of E2F target genes and the Ki67 proliferation marker. CNAs of the CDKN2A-TP53-RB-E2F axis provide a structural basis for increased proliferation in DLBCL, predict outcome with current therapy and suggest targeted treatment approaches. PMID:22975378

  4. Follicular lymphoma transforming into anaplastic diffuse large B-cell lymphoma of oral cavity: A case report with review of literature

    PubMed Central

    Mittal, Megha; Puri, Abhiney; Nangia, Rajat; Sachdeva, Alisha

    2015-01-01

    Follicular lymphoma (FL) is a common form of non-Hodgkin's lymphoma (NHL) with the ability to transform into a more aggressive disease, frequently to B cell-lymphoblastic lymphoma. Diffuse large B-cell lymphoma (DLBCL) is a subtype of NHL, which is characterized by diffuse proliferation of large neoplastic B-lymphocytes. It accounts for 30% of all NHL and its occurrence in the mandible is very rare. It is often seen in young adults, but in the present case, a 50-year-old male patient presented with painless swelling in left lower jaw since 25 days following extraction of left lower molar teeth. There was a history of fever and submandibular lymph nodes were enlarged. On incisional biopsy, features of NHL-like lesion were observed and confirmed by immunohistochemistry using CD20, bcl-2, CD10, CD3, CD5, Ki67 markers to be FL (3A) lymphoma transforming into DLBCL. This is a very uncommon presentation. PMID:26980969

  5. Diffuse large B-cell lymphoma in colon confounded by prior history of colorectal cancer: A case report and literature review

    PubMed Central

    REN, YANLING; CHEN, ZHILU; SU, CHUANYONG; TONG, HONGYAN; QIAN, WENBIN

    2016-01-01

    A 66-year-old male underwent left hemicolectomy for rectal adenocarcinoma in 2008. Five years later he was admitted to hospital with abdominal pain. A computed tomography scan revealed notable thickening of the middle of the ascending colon wall, and colonoscopy revealed an ulcerofungating mass of 3×3 cm in the cecum and extending to the ascending colon. Under the consideration of cancer recurrence, laparoscopic right hemicolectomy was performed directly. Surgical specimens revealed sheets of large pleomorphic lymphoid cells with nuclei of different sizes, nucleoli and mitotic phases visible in most cells. These tested positive for CD45, CD20 and CD79a diffusely, but negative for CD3, CD5, Bcl-2, Bcl-6 and ALK. The Ki-67 proliferation index was 40%. Epstein-Barr virus in situ hybridization did not reveal any positive signals in any of the tumor cells. Based on these findings, the recurrent tumor was diagnosed as diffuse large B-cell lymphoma. The patient could have avoided surgery and received chemotherapy only; however, the case was confounded by the patient's prior history of colorectal cancer due to the rarity of colon lymphoma following rectal cancer in the same patient. It is therefore essential to investigate carefully and differentiate between potential lesions during routine postoperative colonoscopy following colorectal cancer surgery, as patients may present with rare colon lymphoma, which may be confused with a recurrence of colorectal cancer. PMID:26893766

  6. UGT1A1 *6 polymorphism predicts outcome in elderly patients with relapsed or refractory diffuse large B-cell lymphoma treated with carboplatin, dexamethasone, etoposide and irinotecan.

    PubMed

    Yamasaki, Satoshi; Tanimoto, Kazuki; Kohno, Kentarou; Kadowaki, Masanori; Takase, Ken; Kondo, Seiji; Kubota, Akira; Takeshita, Morishige; Okamura, Seiichi

    2015-01-01

    The uridine diphosphate glucuronosyltransferase (UGT) gene 1A1*6 polymorphism, which affects irinotecan metabolism, has been associated with improved survival in lymphoma patients treated with of carboplatin, dexamethasone, etoposide and irinotecan (CDE-11). This study assessed the efficacy of CDE-11 relative to the UGT1A1*6 polymorphism in 27 elderly patients with relapsed or refractory diffuse large B-cell lymphoma who were ineligible for high-dose chemotherapy plus autologous stem cell transplantation. The 2-year survival rate after initial CDE-11 treatment was significantly higher in patients with than without UGT1A1*6 (57% vs. 5%). The most common grade 4 adverse event in patients with the UGT1A1*6 genotypes was neutropenia (88.9%), but there were no gastrointestinal adverse events or treatment-related deaths. Disease progression was the most frequent cause of death. CDE-11 was well tolerated and provided clinical benefit to elderly patients with relapsed or refractory diffuse large B-cell lymphoma. The response to CDE-11 likely correlated with UGT1A1*6 polymorphisms, but further prospective studies are warranted to optimize irinotecan-based chemotherapies relative to UGT1A1 polymorphism. PMID:25055799

  7. Low-Dose PET/CT and Full-Dose Contrast-Enhanced CT at the Initial Staging of Localized Diffuse Large B-Cell Lymphomas

    PubMed Central

    Sabaté-Llobera, Aida; Cortés-Romera, Montserrat; Mercadal, Santiago; Hernández-Gañán, Javier; Pomares, Helena; González-Barca, Eva; Gámez-Cenzano, Cristina

    2016-01-01

    Computed tomography (CT) has been used as the reference imaging technique for the initial staging of diffuse large B-cell lymphoma until recent days, when the introduction of positron emission tomography (PET)/CT imaging as a hybrid technique has become of routine use. However, the performance of both examinations is still common. The aim of this work was to compare the findings between low-dose 2-deoxy-2-(18F)fluoro-d-glucose (18F-FDG) PET/CT and full-dose contrast-enhanced CT (ceCT) in 28 patients with localized diffuse large B-cell lymphoma according to PET/CT findings, in order to avoid the performance of ceCT. For each technique, a comparison in the number of nodal and extranodal involved regions was performed. PET/CT showed more lesions than ceCT in both nodal (41 vs. 36) and extranodal localizations (16 vs. 15). Disease staging according to both techniques was concordant in 22 patients (79%) and discordant in 6 patients (21%), changing treatment management in 3 patients (11%). PET/CT determined a better staging and therapeutic approach, making the performance of an additional ceCT unnecessary. PMID:27559300

  8. Excellent Outcome of Immunomodulation or Bruton’s Tyrosine Kinase Inhibition in Highly Refractory Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type

    PubMed Central

    Accurso, Joseph; Sluzevich, Jason; Menke, David M.; Tun, Han W.

    2015-01-01

    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. PMID:26788279

  9. Autograft HIV-DNA load predicts HIV-1 peripheral reservoir after stem cell transplantation for AIDS-related lymphoma patients.

    PubMed

    Zanussi, Stefania; Bortolin, Maria Teresa; Pratesi, Chiara; Tedeschi, Rosamaria; Basaglia, Giancarlo; Abbruzzese, Luciano; Mazzucato, Mario; Spina, Michele; Vaccher, Emanuela; Tirelli, Umberto; Rupolo, Maurizio; Michieli, Mariagrazia; Di Mascio, Michele; De Paoli, Paolo

    2015-01-01

    Autologous stem cell transplantation (ASCT) is a widely used procedure for AIDS-related lymphomas, and it represents an opportunity to evaluate strategies curing HIV-1 infection. The association of autograft HIV-DNA load with peripheral blood HIV-1 reservoir before ASCT and its contribution in predicting HIV-1 reservoir size and stability during combination antiretroviral therapy (cART) after transplantation are unknown. Aiming to obtain information suggesting new functional cure strategies by ASCT, we retrospectively evaluated HIV-DNA load in autograft and in peripheral blood before and after transplantation in 13 cART-treated HIV-1 relapse/refractoring lymphoma patients. Among them seven discontinued cART after autograft infusion. HIV-DNA was evaluated by a sensitive quantitative real-time polymerase chain reaction (PCR). After debulking chemotherapy/mobilization, the autograft HIV-1 reservoir was higher than and not associated with the peripheral HIV-1 reservoir at baseline [median 215 HIV-DNA copies/10(6) autograft mononuclear cells, range 13-706 vs. 82 HIV-DNA copies/10(6) peripheral blood mononuclear cells (PBMCs), range 13-479, p = 0.03]. After high dose chemotherapy and autograft infusion, HIV-DNA levels reached a plateau between month 6 and 12 of follow-up. No association was found between peripheral HIV-DNA levels at baseline and after infusion in both cART interrupting and not interrupting patients. Only in the last subgroup, a stable significant linear association between autograft and peripheral blood HIV-1 reservoir emerged from month 1 (R(2) = 0.84, p = 0.01) to month 12 follow-up (R(2) = 0.99, p = 0.0005). In summary, autograft HIV-1 reservoir size could be influenced by the mobilization phase and predicts posttransplant peripheral HIV-1 reservoir size in patients on continuous cART. These findings could promote new research on strategies reducing the HIV-1 reservoir by using the ASCT procedure. PMID:25581618

  10. The Prognostic Role and Relationship between E2F1 and SV40 in Diffuse Large B-Cell Lymphoma of Egyptian Patients

    PubMed Central

    Samaka, Rehab M.; Aiad, Hayam A.; Kandil, Mona A.; Asaad, Nancy Y.; Holah, Nanes S.

    2015-01-01

    Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphomas worldwide. The pathogenesis of lymphomas is not yet well understood. SV40 induces malignant transformation by the large T-antigen (L-TAG) and promotes transformation by binding and inactivating p53 and pRb. L-TAG can bind pRb promoting the activation of the E2F1 transcription factor, thus inducing the expression of genes required for the entry to the S phase and leading to cell transformation. This immunohistochemical study was conducted to assess the prognostic role and relationship of SV40 L-TAG and E2F1 in diffuse large B-cell lymphoma (DLBCL) of Egyptian patients. This retrospective study was conducted on 105 tissue specimens including 20 follicular hyperplasia and 85 DLBCL cases. SV40 L-TAG was identified in 3/85 (4%) of DLBCL. High Ki-67 labeling index (Ki-67 LI) and apoptotic count were associated with high E2F1 expression (p<0.001 for all). No significant association was reached between E2F1 and SV40. E2F1 expression proved to be the most and first independent prognostic factor on overall survival of DLBCL patients (HR = 5.79, 95% CI = 2.3–14.6, and p<0.001). Upregulation of E2F1 has been implicated in oncogenesis, prognosis, and prediction of therapeutic response but is not seemingly to have a relationship with the accused SV40. PMID:26601052

  11. The Explorer of Diffuse Galactic Emission (EDGE): Determining the Large-Scale Structure Evolution in the Universe

    NASA Technical Reports Server (NTRS)

    Silverberg, R. F.; Cheng, E. S.; Cottingham, D. A.; Fixsen, D. J.; Meyer, S. S.; Knox, L.; Timbie, P.; Wilson, G.

    2003-01-01

    Measurements of the large-scale anisotropy of the Cosmic Infared Background (CIB) can be used to determine the characteristics of the distribution of galaxies at the largest spatial scales. With this information important tests of galaxy evolution models and primordial structure growth are possible. In this paper, we describe the scientific goals, instrumentation, and operation of EDGE, a mission using an Antarctic Long Duration Balloon (LDB) platform. EDGE will osbserve the anisotropy in the CIB in 8 spectral bands from 270 GHz-1.5 THz with 6 arcminute angular resolution over a region -400 square degrees. EDGE uses a one-meter class off-axis telescope and an array of Frequency Selective Bololeters (FSB) to provide the compact and efficient multi-colar, high sensitivity radiometer required to achieve its scientific objectives.

  12. The influence of personality disorder indication, social support, and grief on alcohol and cocaine use among HIV-positive adults coping with AIDS-related bereavement.

    PubMed

    Hansen, Nathan B; Cavanaugh, Courtenay E; Vaughan, Ellen L; Connell, Christian M; Tate, David C; Sikkema, Kathleen J

    2009-04-01

    Substance use is prevalent among HIV-positive adults and linked to a number of adverse health consequences; however little is known about risk and protective factors that influence substance use among HIV-positive adults coping with AIDS-related bereavement. Using structural equation modeling (SEM), male gender, diagnostic indications of antisocial and borderline personality disorders (PD), and grief severity were tested as risk factors, and social support as a protective factor, for alcohol and cocaine use among a diverse sample of 268 HIV-positive adults enrolled in an intervention for AIDS-related bereavement. Results indicated that the hypothesized model fit the study data. Male gender, PD indication, and social support had direct effects on substance use. PD had significant indirect effects on both alcohol and cocaine use, mediated by social support, but not by grief. Finally, both PD and social support had significant, but opposite, effects on grief. Implications for intervention and prevention efforts are discussed. PMID:17846878

  13. Low absolute lymphocyte count and addition of rituximab confer high risk for interstitial pneumonia in patients with diffuse large B-cell lymphoma.

    PubMed

    Huang, Yu-Chung; Liu, Chia-Jen; Liu, Chun-Yu; Pai, Jih-Tung; Hong, Ying-Chung; Teng, Hao-Wei; Hsiao, Liang-Tsai; Chao, Ta-Chung; Gau, Jyh-Pyng; Liu, Jin-Hwang; Hsu, Hui-Chi; Chiou, Tzeon-Jye; Chen, Po-Min; Yu, Yuan-Bin; Tzeng, Cheng-Hwai

    2011-10-01

    Several small-scale studies have reported pulmonary toxicity among patients with diffuse large B-cell lymphoma (DLBCL) receiving rituximab-containing chemotherapy, though whether the use of rituximab predisposes to interstitial pneumonia (IP) remains unclear. This retrospective study was intended to identify the characteristics and risk factors of IP in patients with DLBCL. Between 2000 and 2009, 529 consecutive patients with DLBCL receiving first-line tri-weekly COP- or CHOP-based chemotherapy with or without rituximab were enrolled as subjects. IP was defined as diffuse pulmonary interstitial infiltrates found on computed tomography scans in conjunction with respiratory symptoms. IP was observed in 26 patients (4.9%), six of whom were confirmed with Pneumocystis jirovecii pneumonia. The median number of chemotherapy courses before IP was four cycles. Using multivariate analysis, absolute lymphocyte count less than 1×10(9)/l at diagnosis [odds ratio (OR) 2.75, p=0.014] and the addition of rituximab to chemotherapy (OR 4.56, p=0.003) were identified as independent risk factors for IP. In conclusion, the incidence of IP is increased in patients with DLBCL receiving rituximab-containing chemotherapy. Specific subgroups with lymphopenia at diagnosis may justify close scrutiny to detect pulmonary complications. PMID:21647583

  14. Derivation of a Large Isotopic Diffuse Sky Emission Component at 1.25 and 2.2um from the COBE/DIRBE Data

    NASA Astrophysics Data System (ADS)

    Sano, K.; Kawara, K.; Matsuura, S.; Kataza, H.; Arai, T.; Matsuoka, Y.

    2015-10-01

    Using all-sky maps obtained with COBE/DIRBE, we reanalyzed the diffuse sky brightness at 1.25 and 2.2 μ {{m}}, which consists of zodiacal light, diffuse Galactic light (DGL), integrated starlight (ISL), and isotropic emission including the extragalactic background light. Our new analysis including an improved estimate of the DGL and the ISL with the 2MASS data showed that deviations of the isotropic emission from isotropy were less than 10% in the entire sky at high Galactic latitude (| b| \\gt 35^\\circ ). We derived the DGL to 100 μm brightness ratios of ∼4.79 and ∼1.49 n W m‑2 MJy‑1 at 1.25 and 2.2 μm, respectively. The result of our analysis revealed a significantly large isotropic component at 1.25 and 2.2 μ {{m}} with intensities of 60.15 ± 16.14 and 27.68+/- 6.21 {{n}} {{W}} {{{m}}}-2 {{sr}}-1, respectively. This intensity is larger than the integrated galaxy light, upper limits from γ-ray observation, and potential contribution from exotic sources (i.e., Population III stars, intrahalo light, direct collapse black holes, and dark stars). We therefore conclude that the excess light may originate from the local universe: the Milky Way and/or the solar system.

  15. A comparison of HIV/AIDS-related stigma in four countries: Negative attitudes and perceived acts of discrimination towards people living with HIV/AIDS☆

    PubMed Central

    Genberg, Becky L.; Hlavka, Zdenek; Konda, Kelika A.; Maman, Suzanne; Chariyalertsak, Suwat; Chingono, Alfred; Mbwambo, Jessie; Modiba, Precious; Van Rooyen, Heidi; Celentano, David D.

    2010-01-01

    HIV/AIDS-related stigma and discrimination have a substantial impact on people living with HIV/AIDS (PLHA). The objectives of this study were: (1) to determine the associations of two constructs of HIV/AIDS-related stigma and discrimination (negative attitudes towards PLHA and perceived acts of discrimination towards PLHA) with previous history of HIV testing, knowledge of antiretroviral therapies (ARVs) and communication regarding HIV/AIDS and (2) to compare these two constructs across the five research sites with respect to differing levels of HIV prevalence and ARV coverage, using data presented from the baseline survey of U.S. National Institute of Mental Health (NIMH) Project Accept, a four-country HIV prevention trial in Sub-Saharan Africa (Tanzania, Zimbabwe and South Africa) and northern Thailand. A household probability sample of 14,203 participants completed a survey including a scale measuring HIV/AIDS-related stigma and discrimination. Logistic regression models determined the associations between negative attitudes and perceived discrimination with individual history of HIV testing, knowledge of ARVs and communication regarding HIV/AIDS. Spearman's correlation coefficients determined the relationships between negative attitudes and perceived discrimination and HIV prevalence and ARV coverage at the site-level. Negative attitudes were related to never having tested for HIV, lacking knowledge of ARVs, and never having discussed HIV/AIDS. More negative attitudes were found in sites with the lowest HIV prevalence (i.e., Tanzania and Thailand) and more perceived discrimination against PLHA was found in sites with the lowest ARV coverage (i.e., Tanzania and Zimbabwe). Programs that promote widespread HIV testing and discussion of HIV/AIDS, as well as education regarding and universal access to ARVs, may reduce HIV/AIDS-related stigma and discrimination. PMID:19427086

  16. Validity and Reliability of Persian Version of HIV/AIDS Related Stigma Scale for People Living With HIV/AIDS in Iran

    PubMed Central

    Pourmarzi, Davoud; Khoramirad, Ashraf; Ahmari Tehran, Hoda; Abedini, Zahra

    2015-01-01

    Objective: To assess the perceived HIV/AIDS related stigma a comprehensive and well developed stigma instrument is necessary. This study aimed to assess validity and reliability of the Persian version of HIV/AIDS related stigma scale which was developed by Kang et al for people living with HIV/AIDS in Iran. Materials and methods: Thescale was forward translatedby two bilingual academic members then both translations were discussed by expert team. Back-translation was done by two other bilingual translators then we carried out discussion with both of them. To evaluate understandability the scale was administered to 10 Persons Living with HIV/AIDS (PLWHA). Final Persian version was administered to 80 PLWHA in Qom, Iran in 2014. Test–retest reliability was assessed in a sample of 20 PLWHA after a week by intra-class correlation coefficient (ICC). Results: Cronbach’s alpha coefficient for overall scale was 0.85. Also Cronbach’s alpha coefficients for the five subscales were as follows: social rejection (9 items, α = 0.84), negative self-worth (4 items, α = 0.70), perceived interpersonal insecurity (2 items, α = 0.57), financial insecurity (3 items, α = 0.70), discretionary disclosure (2 items, α = 0.83). Test–retest reliability was also approved with ICC = 0.78. Correlation between items and their hypothesized subscale is greater than 0.5. Correlation between an item and its own subscale was significantly higher than its correlation with other subscales. Conclusion: This study demonstrate that the Persian version of HIV/AIDS related stigma scale is valid and reliable to assess HIV/AIDS related stigma perceived by people living whit HIV/AIDS in Iran. PMID:27047562

  17. A comparison of HIV/AIDS-related stigma in four countries: negative attitudes and perceived acts of discrimination towards people living with HIV/AIDS.

    PubMed

    Genberg, Becky L; Hlavka, Zdenek; Konda, Kelika A; Maman, Suzanne; Chariyalertsak, Suwat; Chingono, Alfred; Mbwambo, Jessie; Modiba, Precious; Van Rooyen, Heidi; Celentano, David D

    2009-06-01

    HIV/AIDS-related stigma and discrimination have a substantial impact on people living with HIV/AIDS (PLHA). The objectives of this study were: (1) to determine the associations of two constructs of HIV/AIDS-related stigma and discrimination (negative attitudes towards PLHA and perceived acts of discrimination towards PLHA) with previous history of HIV testing, knowledge of antiretroviral therapies (ARVs) and communication regarding HIV/AIDS and (2) to compare these two constructs across the five research sites with respect to differing levels of HIV prevalence and ARV coverage, using data presented from the baseline survey of U.S. National Institute of Mental Health (NIMH) Project Accept, a four-country HIV prevention trial in Sub-Saharan Africa (Tanzania, Zimbabwe and South Africa) and northern Thailand. A household probability sample of 14,203 participants completed a survey including a scale measuring HIV/AIDS-related stigma and discrimination. Logistic regression models determined the associations between negative attitudes and perceived discrimination with individual history of HIV testing, knowledge of ARVs and communication regarding HIV/AIDS. Spearman's correlation coefficients determined the relationships between negative attitudes and perceived discrimination and HIV prevalence and ARV coverage at the site-level. Negative attitudes were related to never having tested for HIV, lacking knowledge of ARVs, and never having discussed HIV/AIDS. More negative attitudes were found in sites with the lowest HIV prevalence (i.e., Tanzania and Thailand) and more perceived discrimination against PLHA was found in sites with the lowest ARV coverage (i.e., Tanzania and Zimbabwe). Programs that promote widespread HIV testing and discussion of HIV/AIDS, as well as education regarding and universal access to ARVs, may reduce HIV/AIDS-related stigma and discrimination. PMID:19427086

  18. Involved Field Radiation After Autologous Stem Cell Transplant for Diffuse Large B-Cell Lymphoma in the Rituximab Era

    SciTech Connect

    Biswas, Tithi; Dhakal, Sughosh; Chen Rui; Hyrien, Ollivier; Bernstein, Steven; Friedberg, Jonathan W.; Fisher, Richard I.; Liesveld, Jane; Phillips, Gordon; Constine, Louis S.

    2010-05-01

    Purpose: For patients with recurrent or refractory large B-cell non-Hodgkin's lymphoma, high-dose chemotherapy and autologous stem cell transplant (ASCT) is the treatment of choice. We evaluated the role of involved field radiation therapy (IFRT) post-ASCT for patients initially induced with cyclophosphamide, adriamycin, vincristine, and prednisone (CHOP) or, more recently, rituximab-CHOP (R-CHOP). Materials and Methods: Between May 1992 and April 2005, 176 patients underwent ASCT for recurrent or refractory large B-cell non-Hodgkin's lymphoma; 164 patients were evaluable for endpoint analysis. Fifty percent of the CHOP group (n = 131), and 39% of the R-CHOP group (n = 33), received IFRT. Follow-up from the time of transplant was a median/mean of 1.7/3 years (range, 0.03-13 years). Results: The 5-year overall survival (OS) and disease-specific survival (DSS) improved with IFRT in both the R-CHOP (p = 0.006 and 0.02, respectively) and CHOP (p = 0.02 and p = 0.04, respectively) groups. IFRT was associated with a 10% (p = 0.17) reduction in local failure, alone or with a distant site. On univariate analysis, IFRT was associated with superior OS (hazard ratio [HR] = 0.50 [95% CI 0.32, 0.78]; p = 0.002) and DSS (HR = 0.53 [95% CI 0.33, 0.86]; p = 0.009). Presence of B symptoms was adverse (p = 0.03). On multivariate analysis, only IFRT was associated with significant improvement in OS (HR = 0.35 [0.18, 0.68]; p = 0.002) and DSS (HR = 0.39 [95% CI 0.18, 0.84]; p = 0.01). Conclusions: Recognizing that positive and negative patient selection bias exists for the use of IFRT post-ASCT, patients initially treated with CHOP or R-CHOP and who undergo ASCT for recurrent or refractory disease may benefit from subsequent IFRT presumably due to enhanced local control that can translate into a survival advantage.

  19. Diffusion-weighted MRI in early chemotherapy response evaluation of patients with diffuse large B-cell lymphoma--a pilot study: comparison with 2-deoxy-2-fluoro- D-glucose-positron emission tomography/computed tomography.

    PubMed

    Wu, Xingchen; Kellokumpu-Lehtinen, Pirkko-Liisa; Pertovaara, Hannu; Korkola, Pasi; Soimakallio, Seppo; Eskola, Hannu; Dastidar, Prasun

    2011-12-01

    To determine the feasibility of diffusion-weighted MRI (DWI) in the evaluation of the early chemotherapeutic response in patients with aggressive non-Hodgkin's lymphoma (NHL), eight patients with histologically proven diffuse large B-cell lymphoma were imaged by MRI, including DWI, and positron emission tomography/computed tomography (PET/CT) before treatment (E1), and after 1 week (E2) and two cycles (E3) of chemotherapy. In all patients, whole-body screening using T(1) - and T(2) -weighted images in the coronal plane was performed. To quantitatively evaluate the chemotherapeutic response, axial images including DWI were acquired. Apparent diffusion coefficient (ADC) maps were reconstructed, and the ADC value of the tumor was measured. In addition, the tumor volume was estimated on axial T(2) -weighted images. The maximum standardized uptake value (SUV(max) ) and active tumor volume were measured on fused PET/CT images. Lymphomas showed high signal intensity on DW images and low signal intensity on ADC maps, except for necrotic foci. The mean pre-therapy ADC was 0.71 × 10(-3) mm(2) /s; it increased by 77% at E2 (p < 0.05) and 24% more at E3 (insignificant); the total increase was 106% (p < 0.05). The mean tumor volume by MRI was 276 mL at baseline; it decreased by 58% at E2 (p < 0.05) and 65% more at E3 (p < 0.05), giving a total decrease of 84% (p < 0.05). All the imaged pre-therapy tumors were strongly positive on PET/CT, with a mean SUV(max) of 20. The SUV(max) decreased by 60% at E2 (p < 0.05) and 59% more at E3 (p < 0.05), giving a total decrease of 83% (p < 0.05). The active tumor burden decreased by 66% at E2 (p < 0.05). At baseline, both central and peripheral tumor ADC values correlated inversely with SUV(max) (p < 0.05), and also correlated inversely with active tumor burden on PET/CT and with tumor volume on MRI at E2 (p < 0.05). In conclusion, the results of DWI in combination with whole-body MRI were

  20. The feeble giant. Discovery of a large and diffuse Milky Way dwarf galaxy in the constellation of Crater

    NASA Astrophysics Data System (ADS)

    Torrealba, G.; Koposov, S. E.; Belokurov, V.; Irwin, M.

    2016-07-01

    We announce the discovery of the Crater 2 dwarf galaxy, identified in imaging data of the VLT Survey Telescope ATLAS survey. Given its half-light radius of ˜1100 pc, Crater 2 is the fourth largest satellite of the Milky Way, surpassed only by the Large Magellanic Cloud, Small Magellanic Cloud and the Sgr dwarf. With a total luminosity of MV ≈ -8, this galaxy is also one of the lowest surface brightness dwarfs. Falling under the nominal detection boundary of 30 mag arcsec-2, it compares in nebulosity to the recently discovered Tuc 2 and Tuc IV and UMa II. Crater 2 is located ˜120 kpc from the Sun and appears to be aligned in 3D with the enigmatic globular cluster Crater, the pair of ultrafaint dwarfs Leo IV and Leo V and the classical dwarf Leo II. We argue that such arrangement is probably not accidental and, in fact, can be viewed as the evidence for the accretion of the Crater-Leo group.

  1. A qualitative analysis of barriers to accessing HIV/AIDS-related services among newly diagnosed HIV-positive men who have sex with men in China.

    PubMed

    Li, Haochu Howard; Holroyd, Eleanor; Li, Xiaoming; Lau, Joseph

    2015-01-01

    In China, specific HIV/AIDS-related services have been in place since 2004. However, utilisation of these services remains limited among people living with HIV. We explored barriers to accessing HIV/AIDS-related services from the perspective of newly diagnosed HIV-positive men who have sex with men. We conducted repeated in-depth interviews with 31 newly diagnosed HIV-positive men who have sex with men, using the socio-ecological framework and thematic content analysis. Multiple barriers for utilisation of HIV/AIDS-related services were identified, including perceptions of subjective health and poor quality of services, mental and emotional health problems, lack of trust and understanding of the services on offer, low economic status, lack of insurance, and high medical fees, being refused access to services, and restrictive attendance policies. The findings provide information on potential multi-level obstacles preventing newly diagnosed HIV-positive men who have sex with men to use services that they need. It is recommended that policy makers should create a trustful and non-discriminating environment and services integrating physical and mental healthcare. PMID:24626063

  2. Rare and persistent Rhodococcus equi infection in a diffuse large B cell lymphoma patient: case report and review of the literature

    PubMed Central

    Zhang, Junli; Xu, Jing; Du, Xiaoxing; Yu, Yunsong

    2014-01-01

    Rhodococcus equi (R. equi) is an uncommon gram positive organism. It is a rare but recognized pathogen in humans and has emerged as an important cause of morbidity and mortality among immunocompromised patients. Generally, R. equi infection needs combined treatment with effective antibiotics, and often requires the immune adjuvant therapy. Here we reported a 49-year-old man presented dyspnea with fever, skin ulcer for 5 months, and the final diagnosis was diffuse large B cell lymphoma with R. equi septicemia and pneumonia, the treatment was failure, the blood culture was always positive during the course of disease, though he was given combined treatment with effective antibiotics, perhaps the immune reconstitution or immune supportive treatment was more important. PMID:25590009

  3. Combination of YM155, a survivin suppressant with a STAT3 inhibitor: a new strategy to treat diffuse large B-cell lymphoma.

    PubMed

    Kaneko, Naoki; Kita, Aya; Yamanaka, Kentaro; Mori, Masamichi

    2013-09-01

    Survivin and STAT3 pathway have been reported to be important for the growth of diffuse large B-cell lymphoma (DLBCL) cells. Here we investigated the antitumor activity of sepantronium bromide (YM155), a survivin suppressant, in combination with STAT3 inhibitors in DLBCL cell lines in vitro. YM155 synergistically enhanced STAT3 inhibitors (AG490 and STA-21)-induced apoptosis in DLBCL cell lines. Moreover, rituximab, which shows inhibitory activity against STAT3, also sensitized DLBCL cell lines to YM155 regardless of sensitivity to rituximab. These results suggest that combining the inhibition of survivin with STAT3 pathway is an attractive and potentially effective way for the treatment of DLBCL. PMID:23746965

  4. An Unusual Case of Extranodal Diffuse Large B-Cell Lymphoma Infiltrating Skeletal Muscle: A Case Report and Review of the Literature

    PubMed Central

    Hatem, Joseph; Bogusz, Agata M.

    2016-01-01

    Diffuse large B-cell lymphoma is extranodal in approximately 40% of cases, arising in nearly any organ system. DLBCL involvement of soft tissue and in particular skeletal muscle is extremely rare, comprising less than 1% of all extranodal non-Hodgkin lymphomas (NHL). We report a case of a 79-year-old man that presented with a DLBCL of the left triceps. In particular, we describe an unusual histologic appearance of pseudoglandular structures, resembling adenocarcinoma. We performed a review of lymphoma cases involving skeletal muscle diagnosed at our institution over the past 15 years as well as thorough PubMed review of the literature. We discuss the features of lymphoma involving skeletal muscle as it pertains to clinical characteristics, histologic subtype, tumor localization, diagnostic studies, therapy, and outcome. Finally, we highlight the diagnostic difficulties that can present in these rare and often challenging cases. PMID:27247818

  5. Diffuse large B-cell lymphoma transformed from mucosa-associated lymphoid tissue lymphoma arising in a female urethra treated with rituximab for the first time.

    PubMed

    Zahrani, A Al; Abdelsalam, M; Fiaar, A Al; Ibrahim, N; Al-Elawi, A; Muhammad, B

    2012-05-01

    A 30-year-old female patient presented to the gynecology clinic with a small (painless) swelling at the urethral orifice. She underwent surgical excision of the lesion. Pathological examination revealed non-Hodgkin's lymphoma of diffuse large B-cell type and mucosa-associated lymphoid tissue type, stage IE. The patient refused radiotherapy. Accordingly, we started CHOP-R chemotherapy. She received a total of 6 cycles of CHOP and 8 cycles of rituximab. Patient follow-up was done 3 months later through CT scan and cytoscopy confirming the complete remission. The patient has been disease-free for 4 years. We reviewed 26 cases of this rare entity reported previously. PMID:22679430

  6. Body mass index and other anthropometric parameters in patients with diffuse large B-cell lymphoma: physiopathological significance and predictive value in the immunochemotherapy era.

    PubMed

    Sarkozy, Clémentine; Camus, Vincent; Tilly, Hervé; Salles, Gilles; Jardin, Fabrice

    2015-07-01

    Diffuse large B-cell lymphoma (DLBCL) is the most common form of aggressive non-Hodgkin lymphoma, accounting for 30-40% of newly diagnosed cases. Obesity is a well-defined risk factor for DLBCL. However, the impact of body mass index (BMI) on DLBCL prognosis is controversial. Recent studies suggest that skeletal muscle wasting (sarcopenia) or loss of fat mass can be detected by computed tomography (CT) images and is useful for predicting the clinical outcome in several types of cancer including DLBCL. Several hypotheses have been proposed to explain the differences in DLBCL outcome according to BMI or weight that include tolerance to treatment, inflammatory background and chemotherapy or rituximab metabolism. In this review, we summarize the available literature, addressing the impact and physiopathological relevance of simple anthropometric tools including BMI and tissue distribution measurements. We also discuss their relationship with other nutritional parameters and their potential role in the management of patients with DLBCL. PMID:25363401

  7. Unusual Presentation of Epstein-Barr Virus-Positive Diffuse Large B-Cell Non-Hodgkin Lymphoma of the Elderly.

    PubMed

    Hong, Bosun; Petrosyan, Vahe; Kruger, Anton R

    2016-06-01

    This report describes the case of a 76-year-old woman diagnosed with Epstein-Barr virus-positive diffuse large B-cell non-Hodgkin lymphoma of the elderly. She had an unusual presentation of the disease with widespread skeletal muscle, masticatory muscle, and parotid gland involvement and the development of interesting erythematous lesions in the neck during chemotherapy. One month after completion of chemotherapy, positron-emission tomography (PET) showed features of persistent lymphoma, but a repeat PET scan a month later showed no active disease. This case reiterates 2 important points: first, to consider lymphoma a differential diagnosis in masticatory muscle enlargement and second, to question false positivity when interpreting post-treatment PET scan results, especially in the absence of clinical disease. PMID:26850867

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

    PubMed Central

    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

    2011-01-01

    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. PMID:21463120

  9. Leukocytoclastic vasculitis as early manifestation of Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly.

    PubMed

    Zoroquiain, Pablo; González, Sergio; Molgó, Montserrat; Rodríguez, Alejandra; Valbuena, José R

    2012-05-01

    Extensive necrotizing vasculitis (ENV) is a rare paraneoplastic phenomenon, and the majority of cases reported are associated with hematolymphoid neoplasms. Histologically, most cases of ENV represent leukocytoclastic vasculitis (LCV). Here we report the clinicopahological features of a 68-year-old man with ENV associated to a Epstein Barr virus-positive diffuse large B-cell lymphoma (EBV+DLBCL) of the elderly, a newly recognized lymphoproliferative disorder, most likely representing a paraneoplastic manifestation. The patient was treated with standard chemotherapy regimen for malignant lymphoma. Due to the extensive involvement of the extremities by ENV, surgical debridement was not feasible and a novel therapy based on CHITOSAN apposits was initiated with overall good response and subsequent re-epithelization of the skin lesions. The patient died of sepsis secondary to a Pseudomona pneumonia 17 months after diagnosis. PMID:22197862

  10. Cross-Platform Assessment of Genomic Imbalance Confirms the Clinical Relevance of Genomic Complexity and Reveals Loci with Potential Pathogenic Roles in Diffuse Large B-Cell Lymphoma

    PubMed Central

    Dias, Lizalynn M.; Thodima, Venkata; Friedman, Julia; Ma, Charles; Guttapalli, Asha; Mendiratta, Geetu; Siddiqi, Imran N.; Syrbu, Sergei; Chaganti, R. S. K.; Houldsworth, Jane

    2016-01-01

    Genomic copy number alterations (CNAs) in diffuse large B-cell lymphoma (DLBCL) have roles in disease pathogenesis but overall clinical relevance remains unclear. Herein, an unbiased algorithm was uniformly applied across three genome profiling datasets comprising 392 newly-diagnosed DLBCL specimens that defined 32 overlapping CNAs, involving 36 minimal common regions (MCRs). Scoring criteria were established for 50 aberrations within the MCRs while considering peak gains/losses. Application of these criteria to independent datasets revealed novel candidate genes with coordinated expression, such as CNOT2, potentially with pathogenic roles. No one single aberration significantly associated with patient outcome across datasets, but genomic complexity, defined by imbalance in more than one MCR, significantly portended adverse outcome in two of three independent datasets. Thus, the standardized scoring of CNAs currently developed can be uniformly applied across platforms, affording robust validation of genomic imbalance and complexity in DLBCL and overall clinical utility as biomarkers of patient outcome. PMID:26294112

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

    PubMed Central

    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. Typically, these cases share features intermediate between DLBCL and classical BL or include characteristics of both lymphomas. The rarity of such cases poses a tremendous challenge to both pathologists and oncologists because its differential diagnosis has direct implications for management strategies. In this article, we present a “classical unclassifiable lymphoma with features intermediate between DLBCL and BL” in a young male patient and review of literature. PMID:27601842

  12. Primary splenic B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma: A case report

    PubMed Central

    Shi, Feng; Zhou, Quan; Gao, Ying; Cui, Xiang-Qing; Chang, Hong

    2016-01-01

    B-cell lymphoma (BCL), unclassifiable, with features intermediate between diffuse large BCL (DLBCL) and classical Hodgkin's lymphoma (CHL), is a novel entity to the World Health Organization classification system. These tumors are rare aggressive lymphomas that have a poor prognosis. The present study reports the case of a patient with one such lymphoma that occurred in the spleen, which expressed cluster of differentiation (CD)20, CD79α, melanoma associated antigen (mutated) 1, BCL6, CD15 and CD30. Polymerase chain reaction analysis demonstrated a clonal rearrangement of the genes coding for immunoglobulin heavy chains. The tumor cells demonstrated a negative reaction in the Epstein-Barr virus-encoded small RNA assay. Following the diagnosis of unclassifiable BCL, with intermediate features between DLBCL and CHL, the patient received 7 cycles of the CHOP regimen, and so far, has been in good general condition and tumor-free for 17 months. PMID:27602118

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

    PubMed

    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. Typically, these cases share features intermediate between DLBCL and classical BL or include characteristics of both lymphomas. The rarity of such cases poses a tremendous challenge to both pathologists and oncologists because its differential diagnosis has direct implications for management strategies. In this article, we present a "classical unclassifiable lymphoma with features intermediate between DLBCL and BL" in a young male patient and review of literature. PMID:27601842

  14. Neutrophil/Lymphocyte Ratio, Lymphocyte/Monocyte Ratio, and Absolute Lymphocyte Count/Absolute Monocyte Count Prognostic Score in Diffuse Large B-Cell Lymphoma

    PubMed Central

    Ho, Ching-Liang; Lu, Chieh-Sheng; Chen, Jia-Hong; Chen, Yu-Guang; Huang, Tzu-Chuan; Wu, Yi-Ying

    2015-01-01

    Abstract The neutrophil/lymphocyte ratio (NLR), lymphocyte/monocyte ratio (LMR), and absolute lymphocyte count/absolute monocyte count prognostic score (ALC/AMC PS) have been described as the most useful prognostic tools for patients with diffuse large B-cell lymphoma (DLBCL). We retrospectively analyzed 148 Taiwanese patients with newly diagnosed diffuse large B-cell lymphoma under rituximab (R)-CHOP-like regimens from January 2001 to December 2010 at the Tri-Service General Hospital and investigated the utility of these inexpensive tools in our patients. In a univariate analysis, the NLR, LMR, and ALC/AMC PS had significant prognostic value in our DLBCL patients (NLR: 5-year progression-free survival [PFS], P = 0.001; 5-year overall survival [OS], P = 0.007. LMR: PFS, P = 0.003; OS, P = 0.05. ALC/AMC PS: PFS, P < 0.001; OS, P < 0.001). In a separate multivariate analysis, the ALC/AMC PS appeared to interact less with the other clinical factors but retained statistical significance in the survival analysis (PFS, P = 0.023; OS, P = 0.017). The akaike information criterion (AIC) analysis produced scores of 388.773 in the NLR, 387.625 in the LMR, and 372.574 in the ALC/AMC PS. The results suggested that the ALC/AMC PS appears to be more reliable than the NLR and LMR and may provide additional prognostic information when used in conjunction with the International Prognostic Index.

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

    PubMed Central

    Quan, Lina; Chen, Xue; Liu, Aichun; Zhang, Yan; Guo, Xiuchen; Yan, Shujie; Liu, Yue

    2015-01-01

    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. PMID:26361042

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

    PubMed

    Kopáček, Jiří; Hejzlar, Josef; Porcal, Petr; Posch, Maximilian

    2014-02-01

    Using dynamic, mass budget, and empirical models, we quantified sulphate-sulphur (SO4-S) leaching from soils in a large central European catchment (upper Vltava river, Czech Republic) over a 110-year period (1900-2010). SO4-S inputs to soils with synthetic fertilisers and atmospheric deposition increased in the 1950s-1980s, then rapidly decreased (~80%), and remained low since the middle 1990s. The proportion of drained agricultural land rapidly increased from 4 to 43% between the 1950s and 1990s; then the draining ability of the system slowly decreased due to its ageing. Sulphate concentrations in the Vltava exhibited similar trends as the external SO4-S inputs, suggesting that they could be explained by changes in atmospheric and fertiliser S inputs. The available data and modelling, however, showed that (i) internal SO4-S sources (mineralization of soil organic S in the drained agricultural land), (ii) a hysteresis in SO4-S leaching from forest soils (a net S retention at the high S inputs and then a net release at the lowered inputs), and (iii) hydrology must be taken into account. An empirical model was then employed, based on parameters representing hydrology (discharge), external SO4-S sources (inputs by synthetic fertilisers and atmospheric deposition), and internal SO4-S sources (mineralization related to soil drainage). The model explained 84% of the observed variability in annual SO4-S concentrations in the Vltava river during 1900-2010 and showed that forest soils were a net sink (105 kg ha(-1)) while agricultural land was a net source (55 kg ha(-1)) of SO4-S during 1960-2010. In the late 1980s, forest soils changed from a sink to a source of S, and the present release of SO4-S accumulated in forest soils thus delays recovery of surface waters from acidification, while S losses from agricultural soils increase the risk of future S deficiency in S-demanding crops. PMID:24176702

  17. Cardiac Mortality in Patients With Stage I and II Diffuse Large B-Cell Lymphoma Treated With and Without Radiation: A Surveillance, Epidemiology, and End-Results Analysis

    SciTech Connect

    Pugh, Thomas J.; Ballonoff, Ari; Rusthoven, Kyle E.; McCammon, Robert; Kavanagh, Brian; Newman, Francis; Rabinovitch, Rachel

    2010-03-01

    Purpose: Standard therapy for stage I and II diffuse large B-cell lymphoma consists of combined modality therapy with anthracycline-based chemotherapy, anti-CD20 antibody, and radiation therapy (RT). Curative approaches without RT typically utilize more intensive and/or protracted chemotherapy schedules. Anthracycline-based chemotherapy regimens are associated with a dose-dependent risk of left ventricular systolic dysfunction. We hypothesize that patients treated without RT, i.e., those who are treated with greater total chemotherapy cycles and hence cumulative anthracycline exposure, are at increased risk of cardiac mortality. Methods and Materials: The rate of cardiac-specific mortality (CSM) was analyzed in patients with stage I and II diffuse large B-cell lymphoma diagnosed between 1988 and 2004 by querying the National Cancer Institute Surveillance, Epidemiology, and End-Results database. Analyzable data included gender, age, race, stage, presence of extranodal disease, and RT administration. Results: A total of 15,454 patients met selection criteria; 6,021 (39%) patients received RT. The median follow-up was 36 months (range, 6-180 months). The median age was 64 years. The actuarial incidence rates of CSM at 5, 10, and 15 years were 4.3%, 9.0%, and 13.8%, respectively, in patients treated with RT vs. 5.9%, 10.8% and 16.1%, respectively, in patients treated without RT (p < 0.0001; hazard ratio, 1.35; 95% confidence interval [CI]: 1.16-1.56). The increase in cardiac deaths for patients treated without RT persisted throughout the follow-up period. On multivariate analysis, treatment without RT remained independently associated with an increased risk of CSM (Cox hazard ratio, 1.32; 95% CI: 1.13-1.54; p = 0.0005). Conclusions: Increased anthracycline exposure in patients treated only with chemotherapy regimens may result in an increase in cardiac deaths, detectable only through analysis of large sample sizes. Confirmatory evaluation through meta-analysis of

  18. Individual attitudes and perceived social norms: Reports on HIV/AIDS-related stigma among service providers in China

    PubMed Central

    Li, Li; Liang, Li-Jung; Wu, Zunyou; Lin, Chunqing; Wen, Yi

    2009-01-01

    This study examined HIV/AIDS-related stigma among Chinese service providers by comparing their personal attitudes toward people living with HIV/AIDS with their perception of social norms related to people living with HIV/AIDS. We randomly selected three provincial hospitals, four city/prefecture hospitals, 10 county hospitals, 18 township health clinics, and 54 village clinics from Yunnan, China. Doctors and nurses were randomly sampled proportionally to the doctor-nurse ratio of each hospital or clinic. Lab technicians were over-sampled in order to include an adequate representation in the analysis. A total of 1,101 service providers participated in a voluntary, anonymous survey where demographic characteristics, individual attitude and perceived social norms toward people living with HIV/AIDS, discrimination intent at work, general prejudicial attitude and knowledge on HIV/AIDS were measured. A majority of the sample demonstrated a similarity between their personal views and what they thought most people in society believe. Multiple logistic regressions revealed that participants who were younger or reported personal contact with people living with HIV/AIDS were significantly more likely to report personal attitudes toward the population that were more liberal than their perceived social norms. Holding a more liberal personal attitude toward people living with HIV/AIDS than perceived social norms was significantly and negatively related to the level of discrimination intent at work, perceived discrimination at interpersonal level and the level of general prejudicial attitude toward people living with HIV/AIDS. Results underscored the importance of understanding social norms and personal attitudes in studying HIV-related stigma and called for the incorporation of existing human capital into future HIV stigma reduction programs. Cette étude a examiné le VIH/SIDA lié à stigmatisation parmi les agences chinoises fournissant des soins en comparant leurs attitudes

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

    PubMed

    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. PMID:27167532

  20. Replacement of conventional doxorubicin by pegylated liposomal doxorubicin in standard RCHOP chemotherapy for elderly diffuse large B-Cell lymphoma: a retrospective study in China

    PubMed Central

    Zhou, De; Li, Li; Bao, Changqian; Zhu, Jingjing; Zhu, Lixia; Yang, Xiudi; Zheng, Yanlong; Zhou, Meng; Luo, Xuxia; Xie, Wanzhuo; Ye, Xiujin

    2015-01-01

    Diffuse large B-cell lymphoma (DLBCL) is the most frequent type of non-Hodgkin’s lymphoma (NHL) in adults, and approximately 50% of cases of DLBCL occur in patients above the age of 60. Although RCHOP regimen was established as the standard therapy for DLBCL patients, there are still a large number of DLBCL patients who can’t bear the toxicity of doxorubicin, especially in elderly patients. Pegylated liposomal doxorubicin (PLD) offers a new strategy for elderly DLBCL patients. In our study, we reviewed 103 newly diagnosed patients with DLBCL aged between 60 years to 75 years old who were treated with RCHOP (62 cases) or DRCOP (41 cases) regimen. All the patients completed a mean follow-up period of 28 months (range, 2 to 48 months). There was no statistical difference of OS between the DRCOP (78.0%) and RCHOP (72.6%) groups (P = 0.787). And there were less grade 3-4 cardiotoxicity in patients treated with DRCOP (9.8%) than RCHOP regimen (27.4%, P = 0.029). Our findings in this study indicate that the DRCOP regimen offers similar oncologic efficacy when weighed against the standard RCHOP regimen in elderly DLBCL patients, and it might be a more secure treatment for elderly DLBCL patients who have additional risk factors for cardiac diseases. PMID:26885233

  1. Mass-transport-controlled, large-area, uniform deposition of carbon nanofibers and their application in gas diffusion layers of fuel cells.

    PubMed

    Tang, Xian; Xie, Zhiyong; Huang, Qizhong; Chen, Guofen; Hou, Ming; Yi, Baolian

    2015-05-01

    The effect of mass transport on the growth characteristics of large-area vapor-grown carbon nanofibers (CNFs) was investigated by adjusting the substrate deposition angle (α). The catalyst precursor solution was coated onto one side of a 2D porous carbon paper substrate via a decal printing method. The results showed that the CNFs were grown on only one side of the substrate and α was found to significantly affect the growth uniformity. At α = 0°, the growth thickness, the density, the microstructure and the yield of the CNF film were uniform across the substrate surface, whereas the growth uniformity decreased with increasing α, suggesting that the large-area CNF deposition processes were mass-transport-controlled. Computational fluid dynamics simulations of the gas diffusion processes revealed the homogeneous distributions of the carbon-source-gas concentration, pressure, and velocity near the substrate surface at α = 0°, which were the important factors in achieving the mass-transport-limited uniform CNF growth. The homogeneity of the field distributions decreased with increasing α, in accordance with the variation in the growth uniformity with α. When used as a micro-porous layer, the uniform CNF film enabled higher proton exchange membrane fuel cell performance in comparison with commercial carbon black by virtue of its improved electronic and mass-transport properties confirmed by the electrochemical impedance spectroscopy results. PMID:25865711

  2. Large Picture of the Galactic Center Studied by H_3^+: High Ionization Rate, Prevailing Warm and Diffuse Gas, and Non-Rotating Expanding Molecular Ring

    NASA Astrophysics Data System (ADS)

    Oka, Takeshi; Geballe, Thomas R.; Indriolo, Nick

    2013-06-01

    Following our initial studies of the diffuse interstellar medium in the Central Molecular Zone (CMZ) of the Galactic center (GC) toward two remarkable sightlines--one 140 pc to the West of Sgr A* near Sgr E, and the other 85 pc to the East of Sgr A* near Sgr B --we are in the process of using newly identified bright stars with smooth continua suitable for H_3^+ spectroscopy to both fill the gap between these sightlines and expand coverage to wider regions of the CMZ. So far we have identified 43 qualified stars, of which 24 have been at least partially observed (i.e., in at least one spectral setting). The high ionization rate (on the order of ζ˜3×10^{-15} s^{-1}) and the existence of warm (T˜250 K) and diffuse (n≤100 cm^{-3}) gas previously reported in the GC have also been observed in some of the new sightlines, indicating these conditions fill a large portion of the CMZ. The velocity profiles observed in the diffuse clouds, some of which show absorption extending ˜ 140 km s^{-1}, allow us to draw a velocity-longitude diagram. The high-velocity fronts of such a diagram reveal the existence of an expanding molecular ring (EMR) with radius of ˜ 140 pc and velocity of ˜ 140 km s^{-1}. This ring is similar to those previously reported but is qualitatively different in that it is not rotating, suggesting an expulsion rather than the gravitational potential as causing the EMR. Possible relations between our observations and other high energy events will be discussed. T. R. Geballe and T. Oka, ApJ, 709, L70 (2010). T. Oka, T. R. Geballe, M. Goto, T. Usuda, and B. J. McCall ApJ, 632, 882 (2005). N. Kaifu, T. Kato, and T. Iguchi, Nature, 238, 105 (1972). N. Z. Scoville, ApJ, 175, L127 (1972). Y. Sofue, PASJ, 47, 551 (1995).

  3. Differential expression of Toll-like receptor (TLR) and B cell receptor (BCR) signaling molecules in primary diffuse large B-cell lymphoma of the central nervous system.

    PubMed

    Akhter, Ariz; Masir, Noraidah; Elyamany, Ghaleb; Phang, Kean-Chang; Mahe, Etienne; Al-Zahrani, Ali Matar; Shabani-Rad, Meer-Taher; Stewart, Douglas Allan; Mansoor, Adnan

    2015-01-01

    Primary diffuse large B-cell lymphoma of the central nervous system (CNS DLBCL) is a distinct and aggressive lymphoma that is confined to CNS. Since, central nervous system is barrier-protected and immunologically silent; role of TLR/BCR signaling in pathogenesis and biology of CNS DLBCL is intriguing. Genomic mutations in key regulators of TLR/BCR signaling pathway (MYD88/CD79B/CARD11) have recently been reported in this disease. These observations raised possible implications in novel targeted therapies; however, expression pattern of molecules related to TLR/BCR pathways in this lymphoma remains unknown. We have analyzed the expression of 19 genes encoding TLR/BCR pathways and targets in CNS DLBCLs (n = 20) by Nanostring nCounter™ analysis and compared it with expression patterns in purified reactive B-lymphocytes and systemic diffuse large B cell lymphoma (DLBCL) (n = 20). Relative expression of TLR4, TLR5, TLR9, CD79B and BLNK was higher in CNS DLBCLs than in control B-lymphocytes; where as TLR7, MALT1, BCL10, CD79A and LYN was lower in CNS DLBCLs (P < 0.0001). When compared with systemic DLBCL samples, higher expression of TLR9, CD79B, CARD11, LYN and BLNK was noted in CNS DLBCL (>1.5 fold change; P < 0.01). The B cell receptor molecules like BLNK and CD79B were also associated with higher expression of MYD88 dependent TLRs (TLR4/5/9). In conclusion, we have shown over expression of TLR/BCR related genes or their targets, where genomic mutations have commonly been identified in CNS DLBCL. We have also demonstrated that TLR over expression closely relate with up regulation of genes associated with BCR pathway like CD79B/BLNK and CARD11, which play an important role in NF-kB pathway activation. Our results provide an important insight into the possibility of TLR and/or B-cell receptor signaling molecules as possible therapeutic targets in CNS DLBCL. PMID:25391967

  4. Effect of media use on HIV/AIDS-related knowledge and condom use in sub-Saharan Africa: a cross-sectional study.

    PubMed

    Jung, Minsoo; Arya, Monisha; Viswanath, Kasisomayajula

    2013-01-01

    It is known that the level of HIV/AIDS-related knowledge and the degree of condom use varies by socioeconomic status (SES). However, there is limited research on the effect of mass media use on HIV/AIDS-related cognitive and behavioral outcomes in low-income countries and how it might influence the association between SES and HIV-related outcomes. We investigated the moderating effect of media use on the relationship between SES and HIV/AIDS-related knowledge and condom use in sub-Saharan Africa in terms of communication inequalities. Cross-sectional data from the Demographic Health Surveys from 13 sub-Saharan countries (2004-10) were pooled. Gender-stratified multivariable poisson regression of 151,209 women and 68,890 men were used to calculate adjusted relative ratios and 95% confidence intervals for the associations between SES, media use, HIV-related outcomes, and condom use. We found significant disparities in mass media use among people from different SES groups as well as among countries. Education and wealth are strongly and positively associated with awareness of HIV/AIDS and knowledge about transmission and prevention of HIV/AIDS and are significantly associated with condom use. These associations are attenuated when the use of various types of mass media is added to the models, with newspapers showing the strongest effect. The findings of this study suggest that media use has the potential to blunt the impact of socioeconomic status though not completely eliminate it. Thus, we need to pay attention to reducing communication inequalities among social groups and countries to moderate the effect of wealth and SES on HIV/AIDS. PMID:23874598

  5. [RS3PE syndrome associated with senile Epstein-Barr virus-positive diffuse large B cell lymphoma of a patient with colon cancer].

    PubMed

    Shimoyama, Saori; Kuroda, Hiroyuki; Yoshida, Masahiro; Usami, Makoto; Sakamoto, Hiroki; Yamada, Michiko; Fujii, Shigeyuki; Maeda, Masahiro; Fujita, Miri; Nakano, Tatsumi; Kanari, Yusuke; Iyama, Satoshi; Kato, Junji

    2015-11-01

    A 75-year-old woman consulted her doctor in January 2014 because of pain in the dorsum of the hands, elbows, shoulders, and knees, bilaterally, and was diagnosed as having remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome. Although the joint pain improved with low-dose prednisolone administration, she was referred to our department in April of 2014 because she had become aware of swelling of the right cervical lymph node. Biopsy of the lymph node demonstrated that she had Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) of the elderly, and colonoscopy revealed early colon cancer. Also, both the lymphoma and colon cancer stained positive for vascular endothelial growth factor (VEGF). Complete remission was achieved after two courses of R-CHOP, and RS3PE syndrome did not relapse. This case suggested the involvement of VEGF produced by EBV-positive DLBCL in the pathogenesis of RS3PE syndrome. PMID:26666720

  6. Primary bone marrow diffuse large B-cell lymphoma accompanying cold agglutinin disease: A case report with review of the literature.

    PubMed

    Yamashita, Tomoko; Ishida, Mitsuaki; Moro, Hiroko; Yumoto, Hirofumi; Uchibayashi, Sachiko; Yoshii, Miyuki; Nakanishi, Ryota; Okuno, Hiroko; Yoshida, Takashi; Okuno, Takafumi; Hodohara, Keiko; Okabe, Hidetoshi

    2014-01-01

    Cold agglutinin disease (CAD) is a well-recognized complication of lymphoproliferative disorders. It has been previously recognized that cases of primary CAD frequently exhibit underlying malignant lymphoma in the bone marrow. Lymphoplasmacytic lymphoma is the most common subtype of malignant lymphoma; however, diffuse large B-cell lymphoma (DLBCL) has also been documented, albeit extremely rare. The current report presents a case of primary bone marrow DLBCL accompanying CAD. A 76-year-old male presented with fever and fatigue. Laboratory tests revealed anemia and elevated bilirubin and cold agglutinins with a titer of 8,192 at 4°C. Bone marrow biopsy demonstrated DLBCL and systemic surveillance failed to detect tumorous lesions or lymphadenopathy. Following R-THP-COP therapy, cold agglutinins titer was markedly decreased (by <4); however, malignant lymphoma relapsed and cold agglutinin levels increased again (4,096). This is the second documented case of primary bone marrow DLBCL accompanying CAD. Previously, malignant lymphoma exclusively involving the bone marrow, namely primary bone marrow lymphoma (PBML), has been recognized as a rare and aggressive subtype. The analyses of the present study revealed that the incidence of hemolytic anemia in primary bone marrow DLBCL may be high compared with conventional DLBCL. Therefore, additional analyses are required to clarify the clinicopathological features of PBML. PMID:24348825

  7. Prognostic performance of lymphocyte-to-monocyte ratio in diffuse large B-cell lymphoma: an updated meta-analysis of eleven reports

    PubMed Central

    Sun, Hui-Ling; Pan, Yu-Qin; He, Bang-Shun; Nie, Zhen-Lin; Lin, Kang; Peng, Hong-Xin; Cho, William C; Wang, Shu-Kui

    2016-01-01

    Purpose The findings on the prognostic value of lymphocyte-to-monocyte ratio (LMR) in diffuse large B-cell lymphoma (DLBCL) are inconsistent. This meta-analysis was conducted to more precisely evaluate the prognostic significance of LMR in DLBCL. Methods This analysis combined eleven studies with 4,578 patients aiming to assess the association of LMR with overall survival (OS) and progression-free survival (PFS) in DLBCL. Data from studies directly reporting a hazard ratio (HR) with 95% corresponding confidence interval (CI) in multivariate analysis were pooled to estimate the effect. Results Our results suggested that patients with decreased LMR had shorter OS (HR =1.79, 95% CI =1.54–2.08, P<0.001) and PFS (HR =2.21, 95% CI =1.80–2.72, P<0.001) in DLBCL. Stratified analyses indicated that each confounder showed consistent prognostic value in DLBCL. There was no significant heterogeneity for PFS (PH=0.192) and OS (PH=0.212) among the enrolled studies. Conclusion This meta-analysis indicated that decreased LMR might be a marker in the prediction of poor prognosis for patients with DLBCL. PMID:27284252

  8. R-CHOP with Iodine-131 Tositumomab Consolidation for Advanced Stage Diffuse Large B-Cell Lymphoma (DLBCL): SWOG S0433

    PubMed Central

    Friedberg, Jonathan W.; Unger, Joseph M.; Burack, W. Richard; Gopal, Ajay K.; Raju, Robert N.; Nademanee, Auayporn P.; Kaminski, Mark S.; Li, Hongli; Press, Oliver W.; Miller, Thomas P.; Fisher, Richard I.

    2014-01-01

    Radiolabelled antiCD-20 antibodies have demonstrated single agent activity in relapsed diffuse large B-cell lymphoma (DLBCL). The S0433 clinical trial enrolled patients with newly diagnosed, advanced stage or bulky stage II, histologically confirmed DLBCL. Patients received six cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone), two cycles of CHOP, then iodine-131 tositumomab radioimmunotherapy consolidation 30–60 days after completion of chemotherapy. The primary endpoint was two-year progression-free survival (PFS). Eighty-four eligible patients were enrolled, and 56 patients completed the entire course of protocol treatment. Of the 84 patients evaluable for treatment response, 72 (86%, 95% confidence interval [CI]: 76%–92%) achieved a partial response (n=21) or a confirmed (n=41) or unconfirmed (n=10) complete response to therapy. With a median follow-up of 3.9 years, the 2-year PFS estimate is 69% and the 2-year overall survival estimate is 77%. Rituximab levels at time of radioimmunotherapy did not correlate with toxicity or outcome. Twenty percent of patients had double hit features (MYC+; BCL2+) by immunohistochemistry, and had inferior outcome. These current results suggest that the incorporation of novel agents earlier in therapy may ultimately have greater impact in DLBCL, as early progressions, deaths and declining performance status during CHOP chemotherapy limited the number of patients who ultimately could benefit from radioimmunotherapy consolidation. PMID:24749780

  9. Severe and irreversible myelopathy after concurrent systemic and intrathecal nucleoside analogue treatment for refractory diffuse large B-cell lymphoma: A case report and review of the literature.

    PubMed

    Alsdorf, Winfried H; Schmitz, Michael; Schieferdecker, Aneta; Dierlamm, Judith; Bokemeyer, Carsten; Binder, Mascha

    2016-06-01

    We report a patient with refractory diffuse large B-cell lymphoma who developed irreversible, severe spinal neurotoxicity after concurrent treatment with intrathecal and systemic cytarabine. Shortly after concomitant administration of intrathecal triple therapy (MTX, dexamethasone and cytarabine) and high-dose systemic cytarabin (R-DHAP protocol) the patient lost control of bowel and bladder function and developed an ascending, irreversible paraplegia. Infectious or neoplastic diseases of the spinal cord were ruled out. A magnetic resonance imaging scan of the spine resulted in a diagnosis of toxic myelitis. Previously observed cases of spinal neurotoxicity after cytarabine treatment are reviewed as well as current guidelines for the use of intrathecal chemotherapy in high-grade non-Hodgkin lymphoma. In summary, severe spinal neurotoxicity of intrathecal chemotherapy is a rare side-effect, however several studies suggest that the neurotoxicity of cytarabine is significantly enhanced by concurrent intrathecal and high-dose systemic administration. Simultaneous high-dose systemic and intrathecal chemotherapy with cytarabine should therefore be avoided. PMID:25655468

  10. White matter integrity assessed by diffusion tensor tractography in a patient with a large tumor mass but minimal clinical and neuropsychological deficits

    PubMed Central

    Bozzali, Marco; MacPherson, Sarah E.; Cercignani, Mara; Crum, William R.; Shallice, Tim; Rees, Jeremy H.

    2012-01-01

    Summary Diffusion tensor imaging (DTI) tractography and image registration were used to investigate a patient with a massive left-sided brain tumor, whose size was largely disproportionate to his subtle neurological deficits. MRI was obtained from the patient and his healthy identical twin, who acted as anatomical reference for DTI and as a control for quantitative measures. To compensate for the patient’s altered anatomy, seed and way points for probabilistic tractography were drawn on the color-coded direction maps of the healthy twin. Registration, based on the combination of b0-images, T2-weighted and T1-weighted images, was used to identify the corresponding regions in the patient. The corticospinal tract (CST), the superior longitudinal fasciculus (SLF), and the cingulum bundle (CB) showed displaced anatomy. A significant difference was found between fractional anisotropy distribution along the left SLF and CB, but not along the CST. These findings fit well with the patient’s substantial preservation of his motor abilities, while abnormalities of the SLF and CB could explain the subtle but detectable cognitive deficits. PMID:23597438

  11. The impact of FcγRIIa and FcγRIIIa gene polymorphisms on responses to RCHOP chemotherapy in diffuse large B-cell lymphoma patients

    PubMed Central

    ROŽMAN, SAMO; NOVAKOVIĆ, SRDJAN; GRABNAR, IZTOK; CERKOVNIK, PETRA; NOVAKOVIĆ, BARBARA JEZERŠEK

    2016-01-01

    Rituximab is a monoclonal antibody routinely used in the treatment of B-cell non-Hodgkin lymphomas. It mediates antibody-dependent cellular cytotoxicity of B lymphocytes by bridging them with Fcγ receptors (FcγR) on effector cells. Several polymorphisms in the FcγR genes have been identified to influence rituximab binding to FcγR, thus altering its antitumor effect in indolent lymphomas. In the present study, the impact of FcγRIIa and FcγRIIIa polymorphisms on the survival and response to immunochemotherapy consisting of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone was evaluated in diffuse large B-cell lymphoma (DLBCL) patients. A total of 29 Slovenian DLBCL patients were studied. Genotyping was conducted for FcγRIIa-27, FcγRIIa-131, FcγRIIIa-48 and FcγRIIIa-158 polymorphisms. The median follow-up time was 29.7 months (range, 9.7–45.4 months). No significant impact of the genotypes was observed on the treatment response, progression-free or overall survival of DLBCL patients. There was a non-significant trend of an improved response to chemotherapy without additional irradiation in patients homozygous for Val at FCγIIIa-158 compared to Phe carriers. The findings of the present study indicate that FcγR polymorphisms have no influence on the survival of DLBCL patients. PMID:27123112

  12. Cerdulatinib, a novel dual SYK/JAK kinase inhibitor, has broad anti-tumor activity in both ABC and GCB types of diffuse large B cell lymphoma

    PubMed Central

    Ma, Jiao; Xing, Wei; Coffey, Greg; Dresser, Karen; Lu, Kellie; Guo, Ailin; Raca, Gordana; Pandey, Anjali; Conley, Pamela; Yu, Hongbo; Wang, Y. Lynn

    2015-01-01

    B-cell receptor (BCR) and JAK/STAT pathways play critical roles in diffuse large B-cell lymphoma (DLBCL). Herein, we investigated the anti-lymphoma activity of cerdulatinib, a novel compound that dually targets SYK and JAK/STAT pathways. On a tissue microarray of 62 primary DLBCL tumors, 58% expressed either phosphorylated SYK or STAT3 or both. SYK and STAT3 are also phosphorylated in a panel of eleven DLBCL cell lines although ABC and GCB subtypes exhibited different JAK/STAT and BCR signaling profiles. In both ABC and GCB cell lines, cerdulatinib induced apoptosis that was associated with caspase-3 and PARP cleavage. The compound also blocked G1/S transition and caused cell cycle arrest, accompanied by inhibition of RB phosphorylation and down-regulation of cyclin E. Phosphorylation of BCR components and STAT3 was sensitive to cerdulatinib in both ABC and GCB cell lines under stimulated conditions. Importantly, JAK/STAT and BCR signaling can be blocked by cerdulatinib in primary GCB and non-GCB DLBCL tumor cells that were accompanied by cell death. Our work provides mechanistic insights into the actions of cerdulatinib, suggesting that the drug has a broad anti-tumor activity in both ABC and GCB DLBCL, at least in part by inhibiting SYK and JAK pathways. PMID:26575169

  13. Comparative Gene Expression Profiling Identifies Common Molecular Signatures of NF-κB Activation in Canine and Human Diffuse Large B Cell Lymphoma (DLBCL)

    PubMed Central

    Mudaliar, Manikhandan A. V.; Haggart, Ross D.; Miele, Gino; Sellar, Grant; Tan, Karen A. L.; Goodlad, John R.; Milne, Elspeth; Vail, David M.; Kurzman, Ilene

    2013-01-01

    We present the first comparison of global transcriptional changes in canine and human diffuse large B-cell lymphoma (DLBCL), with particular reference to the nuclear factor-kappa B (NF-κB) pathway. Microarray data generated from canine DLBCL and normal lymph nodes were used for differential expression, co-expression and pathway analyses, and compared with analysis of microarray data from human healthy and DLBCL lymph nodes. The comparisons at gene level were performed by mapping the probesets in canine microarrays to orthologous genes in humans and vice versa. A considerable number of differentially expressed genes between canine lymphoma and healthy lymph node samples were also found differentially expressed between human DLBCL and healthy lymph node samples. Principal component analysis using a literature-derived NF-κB target gene set mapped to orthologous canine array probesets and human array probesets clearly separated the healthy and cancer samples in both datasets. The analysis demonstrated that for both human and canine DLBCL there is activation of the NF-κB/p65 canonical pathway, indicating that canine lymphoma could be used as a model to study NF-κB-targeted therapeutics for human lymphoma. To validate this, tissue arrays were generated for canine and human NHL and immunohistochemistry was employed to assess NF-κB activation status. In addition, human and canine B-cell lymphoma lines were assessed for NF-κB activity and the effects of NF-κB inhibition. PMID:24023754

  14. MYC protein expression is associated with poor prognosis in primary diffuse large B-cell lymphoma of the central nervous system.

    PubMed

    Tapia, Gustavo; Baptista, Maria-Joao; Muñoz-Marmol, Ana-Maria; Gaafar, Ayman; Puente-Pomposo, Maria; Garcia, Olga; Marginet-Flinch, Ruth; Sanz, Carolina; Navarro, Jose-Tomas; Sancho, Juan-Manuel; Ribera, Josep-Maria; Ariza, Aurelio; Mate, Jose-Luis

    2015-07-01

    MYC and BCL2 gene translocations and protein expression have recently demonstrated to be of prognostic significance in systemic diffuse large B-cell lymphoma (DLBCL). However, their role in primary central nervous system DLBCL (CNS-DLBCL) prognosis has been scarcely analyzed. We studied the immunophenotype, the status of the MYC, BCL2, and BCL6 genes and the clinical features of a series of 42 CNS-DLBCL and evaluated their prognostic significance. We found high MYC protein expression in 43% of cases, and this was associated with lower overall survival (OS). Cases with concurrent expression of MYC and BCL2 showed a lower OS, although the difference did not reach statistical significance. Translocations involving the MYC or BCL2 genes were not detected. The BCL6 gene was frequently translocated, but was unrelated to survival. We conclude that MYC protein expression detected by immunohistochemistry identifies a CNS-DLBCL subset with worse prognosis and may contribute to a more accurate risk stratification of CNS-DLBCL patients. PMID:26010683

  15. Stratifying diffuse large B-cell lymphoma patients treated with chemoimmunotherapy: GCB/non-GCB by immunohistochemistry is still a robust and feasible marker

    PubMed Central

    Batlle-López, Ana; de Villambrosía, Sonia González; Francisco, Mazorra; Malatxeberria, Sefora; Sáez, Anabel; Montalban, Carlos; Sánchez, Lydia; Garcia, Juan F.; González-Barca, Eva; López-Hernández, Andrés; Ruiz-Marcellan, MC; Mollejo, Manuela; Grande, Carlos; Richards, Kristy L.; Hsi, Eric D.; Tzankov, Alexandar; Visco, Carlo; Xu-Monette, Zijun Y.; Cao, Xin; Young, Ken H.; Piris, Miguel Ángel; Conde, Eulogio; Montes-Moreno, Santiago

    2016-01-01

    Diffuse large B cell lymphoma (DLBCL) is a heterogeneous group of aggressive lymphomas that can be classified into three molecular subtypes by gene expression profiling (GEP): GCB, ABC and unclassified. Immunohistochemistry-based cell of origin (COO) classification, as a surrogate for GEP, using three available immunohistochemical algorithms was evaluated in TMA-arranged tissue samples from 297 patients with de novo DLBCL treated by chemoimmunotherapy (R-CHOP and R-CHOP-like regimens). Additionally, the prognostic impacts of MYC, BCL2, IRF4 and BCL6 abnormalities detected by FISH, the relationship between the immunohistochemical COO classification and the immunohistochemical expression of MYC, BCL2 and pSTAT3 proteins and clinical data were evaluated. In our series, non-GCB DLBCL patients had significantly worse progression-free survival (PFS) and overall survival (OS), as calculated using the Choi, Visco-Young and Hans algorithms, indicating that any of these algorithms would be appropriate for identifying patients who require alternative therapies to R-CHOP. Whilst MYC abnormalities had no impact on clinical outcome in the non-GCB subtype, those patients with isolated MYC rearrangements and a GCB-DLBCL phenotype had worse PFS and therefore might benefit from novel treatment approaches. PMID:26910115

  16. Outcome of patients with relapsed diffuse large B-cell lymphoma who fail second-line salvage regimens in the International CORAL study.

    PubMed

    Van Den Neste, E; Schmitz, N; Mounier, N; Gill, D; Linch, D; Trneny, M; Milpied, N; Radford, J; Ketterer, N; Shpilberg, O; Dührsen, U; Ma, D; Brière, J; Thieblemont, C; Salles, G; Moskowitz, C H; Glass, B; Gisselbrecht, C

    2016-01-01

    Salvage chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard second-line treatment for relapsed and refractory diffuse large B-cell lymphoma (DLBCL). However, the strategy is less clear in patients who require third-line treatment. Updated outcomes of 203 patients who could not proceed to scheduled ASCT in the Collaborative Trial in Relapsed Aggressive Lymphoma (CORAL) are herein reviewed. In the intent-to-treat analysis, overall response rate to third-line chemotherapy was 39%, with 27% CR or CR unconfirmed, and 12% PR. Among the 203 patients, 64 (31.5%) were eventually transplanted (ASCT 56, allogeneic SCT 8). Median overall survival (OS) of the entire population was 4.4 months. OS was significantly improved in patients with lower tertiary International Prognostic Index (IPI), patients responding to third-line treatment and patients transplanted with a 1-year OS of 41.6% compared with 16.3% for the not transplanted (P<0.0001). In multivariate analysis, IPI at relapse (hazard ratio (HR) 2.409) and transplantation (HR 0.375) independently predicted OS. Third-line salvage chemotherapy can lead to response followed by transplantation and long-term survival in DLBCL patients. However, improvement of salvage efficacy is an urgent need with new drugs. PMID:26367239

  17. Prognostic significance of PRAME expression based on immunohistochemistry for diffuse large B-cell lymphoma patients treated with R-CHOP therapy.

    PubMed

    Mitsuhashi, Kenjiro; Masuda, Akihiro; Wang, Yan-Hua; Shiseki, Masayuki; Motoji, Toshiko

    2014-07-01

    The preferentially expressed antigen of melanoma (PRAME), a tumor-associated antigen, is considered a prognostic marker for various human malignancies. The prognostic significance of PRAME expression for diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab-containing chemotherapy has not been evaluated to date, and the ability of immunohistochemistry (IHC) to detect PRAME expression in these patients has not yet been studied, although IHC is simple to perform in clinical practice. We evaluated the prognostic significance of PRAME expression based on IHC analysis in 160 DLBCL patients treated with R-CHOP therapy. There was a significant association between higher PRAME expression and shorter progression-free survival (PFS), and a trend toward shorter overall survival (OS) in patients with higher PRAME expression than that in patients with lower PRAME expression (5-year PFS, 48.1 vs. 61.1 %; 5-year OS, 65.6 vs. 79.1 %). Patients with high PRAME expression tended to have lower chemotherapeutic responses. Thus, IHC is useful for detecting and assessing PRAME expression in DLBCL. Further, we found a positive correlation between IHC and quantitative real-time RT-PCR measurements of PRAME expression. Our findings indicate that IHC results of PRAME expression can be a novel prognostic maker in DLBCL patients treated with R-CHOP therapy. PMID:24820636

  18. Metachronous Diffuse Large B-Cell Lymphoma and Kaposi Sarcoma of the Right Eyelid and Lacrimal Gland in a Patient with Granulomatous Common Variable Immunodeficiency

    PubMed Central

    Stenton, Sophie; Fernando, Malee; Currie, Zanna; Mudhar, Hardeep Singh

    2016-01-01

    Purpose To describe the ophthalmic and histopathological features of a female with granulomatous common variable immunodeficiency (CVID) who presented with upper-lid swelling. Procedures The patient underwent a biopsy of the right upper lid/palpebral lacrimal gland with imaging showing a left-sided nasopharyngeal mass, multiple lymph nodes within the mediastinum, bilateral lung nodules and a peritoneal nodule in the right iliac fossa. The right upper-lid swelling progressed and was subject to a second biopsy. Results The first right upper-lid biopsy revealed a diffuse large B-cell lymphoma (DLBCL), confirmed with clonal IgH gene rearrangement with PCR. The nasopharyngeal mass and lymph nodes were suspected clinically to be DLBCL. However, a biopsy of the nasopharyngeal mass showed Kaposi sarcoma (KS). The second biopsy of the right upper lid/palpebral lacrimal gland revealed KS with no evidence of DLBCL. Conclusion This is the first documentation of periocular/orbital metachronous DLBCL and KS in a patient with granulomatous CVID. We discuss the role of fluctuating immunity in CVID to explain the spontaneous regression of the DLBCL and the varying clinical picture. PMID:27239466

  19. M2 tumour-associated macrophages contribute to tumour progression via legumain remodelling the extracellular matrix in diffuse large B cell lymphoma

    PubMed Central

    Shen, Long; Li, Honghao; Shi, Yuzhi; Wang, Dekun; Gong, Junbo; Xun, Jing; Zhou, Sifan; Xiang, Rong; Tan, Xiaoyue

    2016-01-01

    Effects of M2 tumour-associated macrophages on the pathogenesis of diffuse large B cell lymphoma (DLBCL) are still controversial. Our data showed that the number of CD163-positive M2 macrophages correlated negatively with DLBCL prognosis. Macrophage depletion by clodronate liposomes significantly suppressed tumour growth in a xenograft mouse model of DLBCL using OCI-Ly3 cells. Moreover, M2 polarization of macrophages induced legumain expression in U937 cells. Exogenous legumain promoted degradation of fibronectin and collagen I, which was abolished by administration of a legumain inhibitor RR-11a. Overexpression of legumain in Raw 264.7 cells also induced tube formation of endothelial cells in matrigel. In the xenograft mouse model of DLBCL, decreased fibronectin and collagen I, as well as increased legumain expression and angiogenesis were found at the late stage tumours compared with early stage tumours. Co-localization of legumain and fibronectin was observed in the extracellular matrix of tumour tissues. Administration of the legumain inhibitor to the xenograft DLBCL model suppressed tumour growth, angiogenesis and collagen deposition compared with the control. Taken together, our results suggest that M2 tumour-associated macrophages affect degradation of the extracellular matrix and angiogenesis via overexpression of legumain, and therefore play an active role in the progression of DLBCL. PMID:27464733

  20. Prevalence of targetable oncogenic mutations and genomic alterations in Epstein-Barr virus-associated diffuse large B-cell lymphoma of the elderly.

    PubMed

    Gebauer, Niklas; Gebauer, Judith; Hardel, Tim Tristan; Bernard, Veronica; Biersack, Harald; Lehnert, Hendrik; Rades, Dirk; Feller, Alfred Christian; Thorns, Christoph

    2015-04-01

    Epstein-Barr virus (EBV)-associated diffuse large B-cell lymphoma (DLBCL) of the elderly constitutes a provisional clinicopathological entity in the current World Health Organization (WHO) classification and its genomic features remain sparsely characterized. We investigated a cohort of 26 cases of untreated de novo EBV-positive DLBCL of the elderly by high-resolution array-based comparative genomic profiling and fluorescence in situ hybridization (FISH). Moreover, we screened for activating mutations affecting nuclear factor (NF)-κB pathway signaling and chromatin remodeling (EZH2, CD79B, CARD11 and MYD88) due to their impact of gene expression signatures and postulated upcoming therapeutic targetability. We identified an overlap between genomic aberrations previously described to be exclusive features of plasmablastic lymphoma (PL), post-transplant lymphoproliferative disorder (PTLD) and DLBCL, respectively, indicating a close cytogenetic relationship between these entities. Few mutations affecting CD79B and CARD11 and no MYD88 mutations were detectable, hinting at EBV-mediated activation of NF-κB as an alternative to pathologically enforced B-cell receptor signaling in this rare entity. PMID:25030036

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

    PubMed

    Miao, Xiaobing; Wu, Yaxun; Wang, Yuchan; Zhu, Xinghua; Yin, Haibing; He, Yunhua; Li, Chunsun; Liu, Yushan; Lu, Xiaoyun; Chen, Yali; Shen, Rong; Xu, Xiaohong; He, Song

    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(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(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. PMID:27397581

  2. EBV-driven diffuse large B-cell lymphoma confined to the liver in a patient with a history of idiopathic CD4 lymphocytopenia

    PubMed Central

    Dziadzio, Magdalena; Chee, Ronnie; McNamara, Christopher; Deheragoda, Maesha; Wagner, Thomas; Seneviratne, Suranjith L

    2013-01-01

    Idiopathic CD4 lymphocytopenia (ICL) is a rare immunodeficiency disorder. We describe a 49-year-old woman with a history of ICL who developed hepatic Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL). ICL was diagnosed at a time of her presentation with varicella-zoster virus (VZV) meningoencephalitis and chorioretinitis. Her CD4 count subsequently improved but remained at the lower limits of the normal range. Five years later she presented with cough, fever and night-sweat. She was found to have multiple liver nodules on MRI, fluorodeoxyglucose (FDG) avid on the positron emission tomography (PET) CT, histologically defined as DLBCL, EBV positive and of non-germinal centre type. To our knowledge this is the first reported case of EBV-positive DLBCL localised to the liver in the context of ICL. EBV-positive DLBCL typically occurs in immunocompromised individuals. The corticosteroid therapy she received for VZV meningoencephalitis may have contributed to the EBV reactivation with subsequent EBV-driven malignant transformation of B-cells. PMID:23966455

  3. Prognostic significance of survivin and caspase-3 immunohistochemical expression in patients with diffuse large B-cell lymphoma treated with rituximab and CHOP.

    PubMed

    Mitrović, Zdravko; Ilić, Ivana; Aurer, Igor; Kinda, Sandra Bašić; Radman, Ivo; Dotlić, Snježana; Ajduković, Radmila; Labar, Boris

    2011-06-01

    Survivin is an inhibitor of apoptosis whose expression may be associated with inferior outcome in patients with diffuse large B-cell lymphoma (DLBCL) treated without rituximab. Caspase-3 is the final caspase of the apoptotic cascade and its pattern of expression may also be related to patients' outcome. In this study we investigated immunohistochemical expression of survivin and caspase-3 (CPP32) in 57 patients with DLBCL treated with rituximab and CHOP (R-CHOP). According to previously published criteria, we separately analyzed correlation of different types of survivin expression with patients' outcome. Nuclear survivin was expressed in only 26% of cases, cytoplasmic survivin was expressed in 81% of cases while application of immunoreactivity scoring system yielded 58% of survivin positive cases. Caspase-3 was expressed in 77% of cases. There were no significant correlations between any type of survivin expression and response to treatment or survival of the patients. The expression of caspase-3 was also not associated with patients' outcome. We conclude that survivin and caspase-3 have no significant prognostic significance in patients with DLBCL treated with R-CHOP. PMID:20853074

  4. ROBUST: Lenalidomide-R-CHOP versus placebo-R-CHOP in previously untreated ABC-type diffuse large B-cell lymphoma.

    PubMed

    Nowakowski, Grzegorz S; Chiappella, Annalisa; Witzig, Thomas E; Spina, Michele; Gascoyne, Randy D; Zhang, Lei; Flament, Jocelyne; Repici, Jacqueline; Vitolo, Umberto

    2016-07-01

    Activated B-cell-like (ABC) diffuse large B-cell lymphoma (DLBCL), the major constituent of nongerminal center B-cell-like (non-GCB) DLBCL, is associated with poorer survival outcomes than GCB-type DLBCL. In Phase II studies, lenalidomide combined with R-CHOP (R(2)-CHOP) improved outcomes relative to historical R-CHOP in newly diagnosed DLBCL, particularly in non-GCB cases. ROBUST (CC-5013-DLC-002) is a randomized, double-blind, global, Phase III study of oral lenalidomide (15 mg, days 1-14) plus R-CHOP21 × 6 versus placebo-R-CHOP21 × 6 in patients with previously untreated ABC-type DLBCL. Subtyping is done within 3 calendar days by central laboratory gene-expression profiling of formalin-fixed paraffin-embedded biopsy tissue. The primary end point is progression-free survival. Secondary end points include response rates, overall survival and health-related quality of life. PMID:27089170

  5. [Efficacy of CHOP+/-Rituximab-like therapy plus radiation therapy for patients with diffuse large B-cell lymphoma stage I].

    PubMed

    Ueda, Kyoko; Yokoyama, Masahiro; Asai, Hiroaki; Koudaira, Makoto; Yamada, Syuhei; Katsube, Atsushi; Mishima, Yuko; Sakajiri, Sakura; Takeuchi, Kengo; Saotome, Takashi; Terui, Yasuhito; Takahashi, Syunji; Hatake, Kiyohiko

    2010-05-01

    Clinically, R-CHOP-like therapy plus radiation therapy is commonly performed for patients with limited stage diffuse large B-cell lymphoma. However, the efficacy and the safety of the management have not been evaluated properly. In particular, we have few definitive reports about patients with stage I DLBCL. This time we evaluated the effect of CHOP+/-R-like therapy plus radiation therapy, by analyzing 28 patients with stage I DLBCL, retrospectively. 15 patients were treated with the RCHOP-like therapy, and 13 received CHOP-like therapy combined with radiation therapy. A complete response was observed in all of the patients. With a median follow-up time of 14 months, 1-year progression-free survival (PFS) was 100%, and the 1-year overall survival (OS) was 100% for the patients receiving the R-CHOP-like therapy. With a median follow-up time of 68 months, 5-year PFS was 84. 6%, and 5-year OS was 100% for patients receiving the CHOP-like therapy. Since the followup time was not enough and the patient numbers were too few, the benefit of the addition of Rituximab to the CHOP therapy could not be clarified. We need to assess the safety and the efficacy of the combined modality therapy for patients with limited-stage DLBCL by a larger prospective study. PMID:20495315

  6. Central nervous system prophylaxis in patients with aggressive diffuse large B cell lymphoma: an analysis of 3,258 patients in a single center.

    PubMed

    Avilés, Agustin; Jesús Nambo, M; Neri, Natividad

    2013-06-01

    Central nervous system (CNS) relapse continues to be a frequent and usually fatal complication in patients with diffuse large B cell lymphoma (DLBCL). Multiple factors identify the possibility of relapse and justify neurological prophylaxis; however, most of these have not been confirmed. Thus, the use of prophylaxis has not been defined. From 1988 to 2008, 3,258 patients with DLBCL with higher clinical risks and multiple extranodal involvement that have been treated with standard anthracycline-based chemotherapy: CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) or CHOP-R (CHOP plus rituximab) and that achieve complete response were retrospectively analyzed to assess the efficacy of CNS prophylaxis. One thousand five patients received different schedules for CNS prophylaxis, and 2,253 patients did not receive CNS prophylaxis. CNS relapse was similar in patients who receive prophylaxis (6 %) compared to patients who did not receive prophylaxis (5.9 %). Overall survival of patients who either receive or did not receive prophylaxis was not statistically significant: 49 % versus 53 % (p = 0.802). Thus, it seems that CNS prophylaxis did not improve outcome in this special setting of patients, and no prognostic factors to predict the presence of CNS relapse were identified. It is evident that multicentric studies are necessary to define the role of prophylaxis in order to prevent CNS relapse and that the therapeutic procedure will be carefully revised. PMID:23456620

  7. Clinico-biological characterization and outcome of primary nodal and extranodal diffuse large B-cell lymphoma in the rituximab era.

    PubMed

    Gutiérrez-García, Gonzalo; Colomo, Lluis; Villamor, Neus; Arenillas, Leonor; Martínez, Antonio; Cardesa, Teresa; García-Herrera, Adriana; Setoain, Xavier; Rodríguez, Sonia; Ghita, Gabriela; Abrisqueta, Pau; Giné, Eva; Bosch, Francesc; Campo, Elías; Montserrat, Emilio; López-Guillermo, Armando

    2010-07-01

    To study the main clinico-biological characteristics and the outcome of patients with diffuse large B-cell lymphoma (DLBCL) according to the primary site (nodal vs. extranodal), we included 262 patients consecutively diagnosed with DLBCL in a single institution, 5 years before and after immunochemotherapy was considered as the standard treatment. Altogether 116 patients received CHOP (cyclophosphamide, adriamycin, vincristine, and prednisone) and 146 rituximab plus CHOP (R-CHOP). The primary site was the lymph node in 140 patients (53%), Waldeyer's ring (WR) in 22, gastrointestinal (GI) in 33, and other extranodal in 67. The addition of rituximab significantly improved the CR rate in nodal, but not in extranodal, lymphomas. Patients receiving R-CHOP showed higher OS than those treated with CHOP alone (5-year OS: 71% vs. 48%). This difference was maintained in primary nodal (5-year OS: 69% vs. 37%, p < 0.0001), but was not observed in primary extranodal (75% vs. 65%, p = 0.45) lymphomas. The IPI, treatment, and primary site were the main variables for OS in multivariate analysis. In nodal cases, IPI and treatment maintained value, whereas only IPI predicted OS in extranodal cases. In conclusion, immunochemotherapy treatment dramatically improved the outcome of patients with nodal DLBCL; however, its effect was less in primary extranodal cases, so the prognosis of patients with nodal and extranodal lymphomas has been equalized in the rituximab era. PMID:20497002

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

    PubMed Central

    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

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

    PubMed

    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. PMID:24408160

  10. Omacetaxine mepesuccinate induces apoptosis and cell cycle arrest, promotes cell differentiation, and reduces telomerase activity in diffuse large B‑cell lymphoma cells.

    PubMed

    Zhang, Lina; Chen, Zhenzhu; Zuo, Wenli; Zhu, Xinghu; Li, Yufu; Liu, Xinjian; Wei, Xudong

    2016-04-01

    Clinical studies have demonstrated that omacetaxine mepesuccinate exerts beneficial effects on acute myelogenous leukemia. It has been suggested that omacetaxine mepesuccinate, used alone or with interferon‑α or cytarabine, induces remission in patients with chronic myelogenous leukemia. These effects are possibly mediated by its ability to induce apoptosis of leukemia cells and inhibit the activity of telomerase. To determine whether omacetaxine mepesuccinate is beneficial in diffuse large B‑cell lymphoma (DLBCL), two DLBCL cell lines [a germinal center B cell‑like subtype (GCB) and an activated B cell‑like subtype (ABC)] were treated with omacetaxine mepesuccinate at various concentrations for different durations. The present study indicated that omacetaxine mepesuccinate exerts proapoptotic effects in the two cell types in a dose‑ and time‑dependent manner. The ABC subtype demonstrated increased sensitivity compared with the GCB subtype. At 40 ng/ml, omacetaxine mepesuccinate exhibited a marked proapoptotic effect on DLBCL cells compared with the other tumor cells investigated. Furthermore, omacetaxine mepesuccinate induced cell cycle arrest at G0/G1 phase, and promoted cell terminal differentiation of pro‑B cells. The present study also demonstrated that omacetaxine mepesuccinate exerted its antitumor effect by reducing telomerase activity. In conclusion, the present study demonstrated that omacetaxine mepesuccinate may induce apoptosis and cell cycle arrest, promote cell differentiation, and reduce telomerase activity in DLBCL cells, thus aiding the development of omacetaxine mepesuccinate‑based DLBCL therapeutic strategies. PMID:26935769

  11. Omacetaxine mepesuccinate induces apoptosis and cell cycle arrest, promotes cell differentiation, and reduces telomerase activity in diffuse large B-cell lymphoma cells

    PubMed Central

    ZHANG, LINA; CHEN, ZHENZHU; ZUO, WENLI; ZHU, XINGHU; LI, YUFU; LIU, XINJIAN; WEI, XUDONG

    2016-01-01

    Clinical studies have demonstrated that omacetaxine mepesuccinate exerts beneficial effects on acute myelogenous leukemia. It has been suggested that omacetaxine mepesuccinate, used alone or with interferon-α or cytarabine, induces remission in patients with chronic myelogenous leukemia. These effects are possibly mediated by its ability to induce apoptosis of leukemia cells and inhibit the activity of telomerase. To determine whether omacetaxine mepesuccinate is beneficial in diffuse large B-cell lymphoma (DLBCL), two DLBCL cell lines [a germinal center B cell-like subtype (GCB) and an activated B cell-like subtype (ABC)] were treated with omacetaxine mepesuccinate at various concentrations for different durations. The present study indicated that omacetaxine mepesuccinate exerts proapoptotic effects in the two cell types in a dose- and time-dependent manner. The ABC subtype demonstrated increased sensitivity compared with the GCB subtype. At 40 ng/ml, omacetaxine mepesuccinate exhibited a marked proapoptotic effect on DLBCL cells compared with the other tumor cells investigated. Furthermore, omacetaxine mepesuccinate induced cell cycle arrest at G0/G1 phase, and promoted cell terminal differentiation of pro-B cells. The present study also demonstrated that omacetaxine mepesuccinate exerted its antitumor effect by reducing telomerase activity. In conclusion, the present study demonstrated that omacetaxine mepesuccinate may induce apoptosis and cell cycle arrest, promote cell differentiation, and reduce telomerase activity in DLBCL cells, thus aiding the development of omacetaxine mepesuccinate-based DLBCL therapeutic strategies. PMID:26935769

  12. Comparison of Three Chemotherapy Regimens in Elderly Patients with Diffuse Large B Cell Lymphoma: Experience at a Single National Reference Center in Mexico.

    PubMed

    Nolasco-Medina, Diana; Reynoso-Noveron, Nancy; Mohar-Betancourt, Alejandro; Aviles-Salas, Alejandro; García-Perez, Osvaldo; Candelaria, Myrna

    2016-01-01

    Background. Although chemotherapy added to rituximab is a standard of care for diffuse large B cell lymphoma (DLBCL), treatment of patients ≥65 years of age remains controversial due to comorbidities. Methods. This is a retrospective, comparative, nonrandomized study of patients ≥65 years of age, who were diagnosed with DLBCL but not previously treated. Demographic characteristics and comorbidities were analyzed. Three rituximab-containing treatment regimens (standard RCHOP, anthracycline dose-reduced RChOP, and RCOP) were compared. Descriptive analyses were conducted. Survival was calculated with the Kaplan-Meier method, and differences were compared with the log-rank test. Results. In total, 141 patients with a median age of 73.9 years were studied. The three treatment groups had comparable demographic characteristics. The overall response was 77%, 72.5%, and 59% in groups treated with RCHOP, RChOP, and RCOP, respectively. After multivariate analysis, the factors influencing the overall survival were the presence of B symptoms, poor performance status (ECOG ≥ 3), and febrile neutropenia. Factors influencing disease-free survival were febrile neutropenia, high-intermediate and high-risk IPI scores, and treatment without anthracycline. Conclusion. A higher ORR (overall response rate) was achieved with standard RCHOP, which influenced DFS and OS, although it was not statistically significant compared with the other groups. Interventional phase 3 trials testing new molecules in patients aged 70 to 80 years and older are required to improve the prognosis within this growing population. PMID:27478844

  13. A comparison of HLA-identical sibling allogeneic versus autologous transplantation for diffuse large B cell lymphoma: a report from the CIBMTR.

    PubMed

    Lazarus, Hillard M; Zhang, Mei-Jie; Carreras, Jeanette; Hayes-Lattin, Brandon M; Ataergin, Asli Selmin; Bitran, Jacob D; Bolwell, Brian J; Freytes, César O; Gale, Robert Peter; Goldstein, Steven C; Hale, Gregory A; Inwards, David J; Klumpp, Thomas R; Marks, David I; Maziarz, Richard T; McCarthy, Philip L; Pavlovsky, Santiago; Rizzo, J Douglas; Shea, Thomas C; Schouten, Harry C; Slavin, Shimon; Winter, Jane N; van Besien, Koen; Vose, Julie M; Hari, Parameswaran N

    2010-01-01

    We compared outcomes of 916 diffuse large B cell lymphoma (DLBCL) patients aged >or=18 years undergoing first autologous (n = 837) or myeloablative (MA) allogeneic hematopoietic cell transplant (HCT) (n = 79) between 1995 and 2003 reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). Median follow-up was 81 months for allogeneic HCT versus 60 months for autologous HCT. Allogeneic HCT recipients were more likely to have high-risk disease features including higher stage, more prior chemotherapy regimens, and resistant disease. Allogeneic HCT was associated with a higher 1 year treatment-related mortality (TRM) (relative risk [RR] 4.88, 95% confidence interval [CI], 3.21-7.40, P < .001), treatment failure (RR 2.06, 95% CI, 1.54-2.75, P < .001), and mortality (RR 2.75, 95% CI, 2.03-3.72, P < .001). Risk of disease progression was similar in the 2 groups (RR 1.12, 95% CI, 0.73-1.72, P = .59). In fact, for 1-year survivors, no significant differences were observed for TRM, progression, progression-free (PFS) or overall survival (OS). Increased risks of TRM and mortality were associated with older age (>50 years), lower performance score, chemoresistance, and earlier year of transplant. In a cohort of mainly high-risk DLBCL patients, upfront MA allogeneic HCT, although associated with increased early mortality, was associated with a similar risk of disease progression compared to lower risk patients receiving autologous HCT. PMID:20053330

  14. A COMPARISON OF HLA-IDENTICAL SIBLING ALLOGENEIC VERSUS AUTOLOGOUS TRANSPLANTATION FOR DIFFUSE LARGE B-CELL LYMPHOMA: A REPORT FROM THE CIBMTR

    PubMed Central

    Lazarus, Hillard M.; Zhang, Mei-Jie; Carreras, Jeanette; Hayes-Lattin, Brandon M.; Ataergin, Asli Selmin; Bitran, Jacob D.; Bolwell, Brian J.; Freytes, César O.; Gale, Robert Peter; Goldstein, Steven C.; Hale, Gregory A.; Inwards, David J.; Klumpp, Thomas R.; Marks, David I.; Maziarz, Richard T.; McCarthy, Philip L.; Pavlovsky, Santiago; Rizzo, J Douglas; Shea, Thomas C.; Schouten, Harry C.; Slavin, Shimon; Winter, Jane N.; van Besien, Koen; Vose, Julie M.; Hari, Parameswaran N.

    2010-01-01

    We compared outcomes of 916 diffuse large B cell lymphoma (DLBCL) patients age ≥ 18 years undergoing first autologous (n=837) or myeloablative allogeneic hematopoietic cell transplant (HCT) (n=79) between 1995–2003 reported to the CIBMTR. Median follow-up was 81 months for allogeneic HCT vs. 60 months for autologous. Allogeneic HCT recipients were more likely to have high risk disease features including higher stage, more prior chemotherapy regimens and resistant disease. Allogeneic HCT was associated with a higher 1 year treatment-related mortality (TRM) (RR 4.88, 95% CI, 3.21–7.40, p<0.001), treatment failure (RR 2.06, 95% CI, 1.54–2.75, p<0.001) and mortality (RR 2.75, 95% CI, 2.03–3.72, p<0.001). Risk of disease progression was similar in the 2 groups (RR 1.12, 95% CI, 0.73–1.72, p=0.59). In fact, for 1 year survivors, no significant differences were observed for TRM, progression, progression-free or overall survival. Increased risks of TRM and mortality were associated with older age (>50 years), lower performance score, chemoresistance and earlier year of transplant. In a cohort of mainly high risk DLBCL patients, upfront myeloablative allogeneic HCT while associated with increased early mortality was associated with a similar risk of disease progression compared to lower risk patients receiving autologous HCT. PMID:20053330

  15. Interim 18F-fluorodeoxyglucose positron emission tomography in diffuse large B-cell lymphoma: qualitative or quantitative interpretation--where do we stand?

    PubMed

    Meignan, Michel; Itti, Emmanuel; Gallamini, Andrea; Haioun, Corinne

    2009-11-01

    Interim 18F-fluorodeoxyglucose positron emission tomography performed early during the course of therapy in diffuse large B-cell lymphoma is highly predictive of outcome and now used in many clinical trials to validate risk-adapted strategies. However, interpretation criteria of interim PET are not yet appropriately defined for the evaluation of tumor response and chemosensitivity. From the results of our studies, a quantitative approach based on SUV(max) reduction between baseline PET (PET0) and interim PET demonstrated a higher predictive value than visual analysis when PET was performed at two cycles (PET2) but was equivalent to visual analysis at four cycles (PET4). The SUV(max) reduction index at PET2 seems to be the best predictor of the response compared to clinical or molecular prognostic indices. When visual analysis is necessary, the use of an online independent reading network may solve the interobserver variability, but the hurdles of visual analysis deserve an international validation study to confirm the newly proposed criteria. PMID:19863178

  16. EBV-positive diffuse large B-cell lymphoma of the elderly: 2016 update on diagnosis, risk-stratification, and management.

    PubMed

    Castillo, Jorge J; Beltran, Brady E; Miranda, Roberto N; Young, Ken H; Chavez, Julio C; Sotomayor, Eduardo M

    2016-05-01

    Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) of the elderly is a provisional entity included in the 2008 WHO classification of lymphoid neoplasms. It is a disease typically seen in the elderly and thought to be associated with chronic EBV infection and severe immunosuppression with a component of immunosenescence. Recent research, however, has suggested that EBV-positive DLBCL can be seen in younger, immunocompetent patients. The diagnosis of EBV-positive DLBCL of the elderly is made through a careful pathological evaluation. The differential diagnosis includes infectious mononucleosis (specifically in younger patients), lymphomatoid granulomatosis, Hodgkin lymphoma, and gray zone lymphoma, among others. Detection of EBV-encoded RNA (EBER) is considered standard for diagnosis; however, a clear cutoff for positivity has not been defined. The International Prognostic Index (IPI), and the Oyama score can be used for risk-stratification. The Oyama score includes age >70 years and presence of B symptoms. The expression of CD30 is emerging as a potential adverse, and targetable, prognostic factor. Patients with EBV-positive DLBCL should be staged and managed following similar guidelines than patients with EBV-negative DLBCL. It has been suggested, however, that EBV-positive patients have a worse prognosis than EBV-negative counterparts in the era of chemoimmunotherapy. There is an opportunity to study and develop targeted therapy in the management of patients with EBV-positive DLBCL. Am. J. Hematol. 91:530-537, 2016. © 2016 Wiley Periodicals, Inc. PMID:27093913

  17. Colorimetric In Situ Hybridization Identifies MYC Gene Signal Clusters Correlating With Increased Copy Number, mRNA, and Protein in Diffuse Large B-cell Lymphoma

    PubMed Central

    Valentino, Carlo; Kendrick, Samantha; Johnson, Nathalie; Gascoyne, Randy; Chan, Wing C.; Weisenburger, Dennis; Braziel, Rita; Cook, James R.; Tubbs, Raymond; Campo, Elias; Rosenwald, Andreas; Ott, German; Delabie, Jan; Jaffe, Elaine; Zhang, Wenjun; Brunhoeber, Patrick; Nitta, Hiro; Grogan, Tom; Rimsza, Lisa

    2014-01-01

    Abnormalities of the MYC oncogene on chromosome 8 are characteristic of Burkitt lymphoma and other aggressive B-cell lymphomas, including diffuse large B-cell lymphoma (DLBCL). We recently described a colorimetric in situ hybridization (CISH) method for detecting extra copies of the MYC gene in DLBCL and the frequent occurrence of excess copies of discrete MYC signals in the context of diploidy or polyploidy of chromosome 8, which correlated with increased mRNA signals. We further observed enlarged MYC signals, which were counted as a single gene copy but, by their dimension and unusual shape, likely consisted of “clusters” of MYC genes. In this study, we sought to further characterize these clusters of MYC signals by determining whether the presence of these correlated with other genetic features, mRNA levels, protein, and overall survival. We found that MYC clusters correlated with an abnormal MYC locus and with increased mRNA. MYC mRNA correlated with protein levels, and both increased mRNA and protein correlated with poorer overall survival. MYC clusters were seen in both the germinal center and activated B-cell subtypes of DLBCL. Clusters of MYC signals may be an underappreciated, but clinically important, feature of aggressive B-cell lymphomas with potential prognostic and therapeutic relevance. PMID:23355209

  18. Digital PCR for quantification of recurrent and potentially actionable somatic mutations in circulating free DNA from patients with diffuse large B-cell lymphoma.

    PubMed

    Camus, Vincent; Sarafan-Vasseur, Nasrin; Bohers, Elodie; Dubois, Sydney; Mareschal, Sylvain; Bertrand, Philippe; Viailly, Pierre-Julien; Ruminy, Philippe; Maingonnat, Catherine; Lemasle, Emilie; Stamatoullas, Aspasia; Picquenot, Jean-Michel; Cornic, Marie; Beaussire, Ludivine; Bastard, Christian; Frebourg, Thierry; Tilly, Hervé; Jardin, Fabrice

    2016-09-01

    Diffuse large B-cell lymphoma (DLBCL) is an aggressive and heterogeneous malignancy harboring frequent targetable activating somatic mutations. Emerging evidence suggests that circulating cell-free DNA (cfDNA) can be used to detect somatic variants in DLBCL using Next-Generation Sequencing (NGS) experiments. In this proof-of-concept study, we chose to develop simple and valuable digital PCR (dPCR) assays for the detection of recurrent exportin-1 (XPO1) E571K, EZH2 Y641N, and MYD88 L265P mutations in DLBCL patients, thereby identifying patients most likely to potentially benefit from targeted therapies. We demonstrated that our dPCR assays were sufficiently sensitive to detect rare XPO1, EZH2, and MYD88 mutations in plasma cfDNA, with a sensitivity of 0.05%. cfDNA somatic mutation detection by dPCR seems to be a promising technique in the management of DLBCL, in addition to NGS experiments. PMID:26883583

  19. Results of a prospective phase II trial evaluating interim positron emission tomography-guided high dose therapy for poor prognosis diffuse large B-cell lymphoma.

    PubMed

    Stewart, Douglas A; Kloiber, Reinhard; Owen, Carolyn; Bahlis, Nizar J; Duggan, Peter; Mansoor, Adnan; Bence-Bruckler, Isabelle

    2014-09-01

    Patients with diffuse large B-cell lymphoma (DLBCL) with a poor prognosis based upon advanced stage and elevated serum lactate dehydrogenase achieve a 3-4-year progression-free survival (PFS) of only 55%. The role of interim fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET) to guide use of upfront high dose chemotherapy (HDCT) and autologous stem cell transplant (ASCT) for patients with poor prognosis DLBCL is unproven. A prospective phase II clinical trial was designed to evaluate the outcomes of HDCT/ASCT for patients with poor prognosis DLBCL aged 18-65 years who had unfavorable interim restaging PET scans. Of the 70 eligible patients, 36 had unfavorable and 34 favorable interim PET responses, with 3-year PFS rates of 65.2% and 52.7%, respectively. In conclusion, favorable interim PET response as defined in this study is not associated with improved PFS rates for patients with poor prognosis DLBCL treated with RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). A phase III trial evaluating this PET-guided approach is not warranted. PMID:24188476

  20. A potential panel of six-long non-coding RNA signature to improve survival prediction of diffuse large-B-cell lymphoma

    PubMed Central

    Sun, Jie; Cheng, Liang; Shi, Hongbo; Zhang, Zhaoyue; Zhao, Hengqiang; Wang, Zhenzhen; Zhou, Meng

    2016-01-01

    Long non-coding RNAs (lncRNAs) represent an emerging layer of cancer biology and have been implicated in the development and progression of cancers. However, the prognostic significance of lncRNAs in diffuse large-B-cell lymphoma (DLBCL) remains unclear and needs to be systematically investigated. In this study, we obtained and analyzed lncRNA expression profiles in three cohorts of 1043 DLBCL patients by repurposing the publicly available microarray datasets from the Gene Expression Omnibus (GEO) database. In the discovery series of 207 patients, we identified a set of six lncRNAs that was significantly associated with patients’ overall survival (OS) using univariate Cox regression analysis. The six prognostic lncRNAs were combined to form an expression-based six-lncRNA signature which classified patients of the discovery series into the high-risk group and low-risk group with significantly different survival outcome (HR = 2.31, 95% CI = 1.8 to 2.965, p < 0.001). The six-lncRNA signature was further confirmed in the internal testing series and two additional independent datasets with different array platform. Moreover, the prognostic value of the six-lncRNA signature is independent of conventional clinical factors. Functional analysis suggested that six-lncRNA signature may be involved with DLBCL through exerting their regulatory roles in known cancer-related pathways, immune system and signaling molecules interaction. PMID:27292966

  1. Reduced-dose ICE chemotherapy ± rituximab is a safe and effective salvage therapy for fit elderly patients with diffuse large B-cell lymphoma.

    PubMed

    Sarid, Nadav; Joffe, Erel; Gibstein, Lili; Avivi, Irit; Polliack, Aaron; Perry, Chava; Herishanu, Yair

    2016-07-01

    The risk of developing non-Hodgkin lymphoma increases with age, yet elderly patients are under-represented in clinical trials. Here, we evaluate a combination regimen including ifosfamide, carboplatin and etoposide with or without rituximab (ICE ± R) in 32 fit elderly patients (median age 75.6 years) with relapsed or refractory diffuse large B-cell lymphoma. ICE ± R was generally administered in reduced doses and was well tolerated. The overall response rate (ORR) was 53.1% with a complete response (CR) rate of 40.6%. The median progression free survival (PFS) and overall survival (OS) were 3.9 and 17.0 months, respectively. Patients who responded to ICE ± R achieved median PFS of 47.2 months and OS of 78.9 months. Patients ineligible for autologous transplantation who responded to ICE ± R were treated with additional cycles, and achieved a median PFS of 18.9 months and OS of 21.7 months. Previous response to first-line therapy was the strongest predictor of response, PFS and OS to second-line treatment. PMID:26643787

  2. Identification and validation of a two-gene expression index for subtype classification and prognosis in Diffuse Large B-Cell Lymphoma.

    PubMed

    Xu, Qinghua; Tan, Cong; Ni, Shujuan; Wang, Qifeng; Wu, Fei; Liu, Fang; Ye, Xun; Meng, Xia; Sheng, Weiqi; Du, Xiang

    2015-01-01

    The division of diffuse large B-cell lymphoma (DLBCL) into germinal center B-cell-like (GCB) and activated B-cell-like (ABC) subtypes based on gene expression profiling has proved to be a landmark in understanding the pathogenesis of the disease. This study aims to identify a novel biomarker to facilitate the translation of research into clinical practice. Using a training set of 350 patients, we identified a two-gene expression signature, "LIMD1-MYBL1 Index", which is significantly associated with cell-of-origin subtypes and clinical outcome. This two-gene index was further validated in two additional dataset. Tested against the gold standard method, the LIMD1-MYBL1 Index achieved 81% sensitivity, 89% specificity for ABC group and 81% sensitivity, 87% specificity for GCB group. The ABC group had significantly worse overall survival than the GCB group (hazard ratio = 3.5, P = 0.01). Furthermore, the performance of LIMD1-MYBL1 Index was satisfactory compared with common immunohistochemical algorithms. Thus, the LIMD1-MYBL1 Index had considerable clinical value for DLBCL subtype classification and prognosis. Our results might prompt the further development of this two-gene index to a simple assay amenable to routine clinical practice. PMID:25940947

  3. MYC+ diffuse large B-cell lymphoma is not salvaged by classical R-ICE or R-DHAP followed by BEAM plus autologous stem cell transplantation

    PubMed Central

    Cuccuini, Wendy; Briere, Josette; Mounier, Nicolas; Voelker, Hans-Ullrich; Rosenwald, Andreas; Sundstrom, Christer; Cogliatti, Sergio; Hirchaud, Edouard; Ysebaert, Loic; Bron, Dominique; Soulier, Jean; Gaulard, Philippe; Houlgatte, Remi; Gisselbrecht, Christian; Thieblemont, Catherine

    2012-01-01

    Approximately 5–10% of diffuse large B-cell lymphomas (DLBCL) harbor a 8q24/MYC rearrangement (MYC +). We determined the prognostic significance of MYC rearrangement in patients with relapsed/refractory DLBCL prospectively treated by R-ICE or R-DHAP followed by high-dose therapy and autologous stem cell transplantation. Twenty-eight (17%) of the 161 patients analyzed presented a MYC + rearrangement, targeted as either simple hit (25%) or complex hits (n=75%) including MYC/BCL2, MYC/BCL6, and MYC/BCL2/BCL6. Results were statistically highly concordant in matched primary and relapsed biopsies (n=45). Compared to the MYC − DLBCL patients, the MYC + DLBCL patients presented with a more elevated lactico-deshydrogenase level (p=.0006) and a more advanced age-adjusted international pronostic index (p=.0039). The 4-year PFS and OS were significantly lower in the MYC + DLBCL patients than those in the MYC − DLBCL patients, with rates of 18% vs. 42% (p=.0322), and of 29% vs. 62% (p=.0113), respectively. Type of treatment, R-DHAP or R-ICE had no impact on survivals, with 4-year PFS rates of 17% vs. 19% and 4-year OS rates of 26% vs. 31%. In conclusion, MYC rearrangement is an early event in DLBCL. MYC + DLBCL patients have a significant inferior prognosis than MYC − DLBCL patients. Their outcome was not influenced by the proposed salvage therapy. PMID:22408263

  4. M2 tumour-associated macrophages contribute to tumour progression via legumain remodelling the extracellular matrix in diffuse large B cell lymphoma.

    PubMed

    Shen, Long; Li, Honghao; Shi, Yuzhi; Wang, Dekun; Gong, Junbo; Xun, Jing; Zhou, Sifan; Xiang, Rong; Tan, Xiaoyue

    2016-01-01

    Effects of M2 tumour-associated macrophages on the pathogenesis of diffuse large B cell lymphoma (DLBCL) are still controversial. Our data showed that the number of CD163-positive M2 macrophages correlated negatively with DLBCL prognosis. Macrophage depletion by clodronate liposomes significantly suppressed tumour growth in a xenograft mouse model of DLBCL using OCI-Ly3 cells. Moreover, M2 polarization of macrophages induced legumain expression in U937 cells. Exogenous legumain promoted degradation of fibronectin and collagen I, which was abolished by administration of a legumain inhibitor RR-11a. Overexpression of legumain in Raw 264.7 cells also induced tube formation of endothelial cells in matrigel. In the xenograft mouse model of DLBCL, decreased fibronectin and collagen I, as well as increased legumain expression and angiogenesis were found at the late stage tumours compared with early stage tumours. Co-localization of legumain and fibronectin was observed in the extracellular matrix of tumour tissues. Administration of the legumain inhibitor to the xenograft DLBCL model suppressed tumour growth, angiogenesis and collagen deposition compared with the control. Taken together, our results suggest that M2 tumour-associated macrophages affect degradation of the extracellular matrix and angiogenesis via overexpression of legumain, and therefore play an active role in the progression of DLBCL. PMID:27464733

  5. MCL-1-independent mechanisms of synergy between dual PI3K/mTOR and BCL-2 inhibition in diffuse large B cell lymphoma

    PubMed Central

    Lee, J. Scott; Tang, Sarah S.; Ortiz, Veronica; Vo, Thanh-Trang; Fruman, David A.

    2015-01-01

    The PI3K/AKT/mTOR axis promotes survival and is a frequently mutated pathway in cancer. Yet, inhibitors targeting this pathway are insufficient to induce cancer cell death as single agents in some contexts, including diffuse large B cell lymphoma (DLBCL). In these situations, combinations with inhibitors targeting BCL-2 survival proteins (ABT-199 and ABT-263) may hold potential. Indeed, studies have demonstrated marked synergy in contexts where PI3K/mTOR inhibitors suppress expression of the pro-survival protein, MCL-1. In this study, we use BH3 profiling to confirm that BCL-2 and BCL-XL support survival following PI3K pathway inhibition, and that the dual PI3K/mTOR inhibitor BEZ235 strongly synergizes with BCL-2 antagonists in DLBCL. However, we identify an alternative mechanism of synergy between PI3K/mTOR and BCL-2 inhibitors, independent of MCL-1 down-regulation. Instead, we show that suppression of AKT activation by BEZ235 can induce the mitochondrial accumulation of pro-apoptotic BAD and BIM, and that expression of a constitutively active form of AKT prevents sensitization to BCL-2 antagonism. Thus, our work identifies an additional mechanism of synergy between PI3K pathway inhibitors and BCL-2 antagonists that strengthens the rationale for testing this combination in DLBCL. PMID:26460954

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

    PubMed

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

    2014-02-11

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

  7. Stratifying diffuse large B-cell lymphoma patients treated with chemoimmunotherapy: GCB/non-GCB by immunohistochemistry is still a robust and feasible marker.

    PubMed

    Batlle-López, Ana; González de Villambrosía, Sonia; Francisco, Mazorra; Malatxeberria, Sefora; Sáez, Anabel; Montalban, Carlos; Sánchez, Lydia; Garcia, Juan; González-Barca, Eva; López-Hernández, Andrés; Ruiz-Marcellan, M C; Mollejo, Manuela; Grande, Carlos; Richards, Kristy L; Hsi, Eric D; Tzankov, Alexandar; Visco, Carlo; Xu-Monette, Zijun Y; Cao, Xin; Young, Ken H; Piris, Miguel Ángel; Conde, Eulogio; Montes-Moreno, Santiago

    2016-04-01

    Diffuse large B cell lymphoma (DLBCL) is a heterogeneous group of aggressive lymphomas that can be classified into three molecular subtypes by gene expression profiling (GEP): GCB, ABC and unclassified. Immunohistochemistry-based cell of origin (COO) classification, as a surrogate for GEP, using three available immunohistochemical algorithms was evaluated in TMA-arranged tissue samples from 297 patients with de novo DLBCL treated by chemoimmunotherapy (R-CHOP and R-CHOP-like regimens). Additionally, the prognostic impacts of MYC, BCL2, IRF4 and BCL6 abnormalities detected by FISH, the relationship between the immunohistochemical COO classification and the immunohistochemical expression of MYC, BCL2 and pSTAT3 proteins and clinical data were evaluated. In our series, non-GCB DLBCL patients had significantly worse progression-free survival (PFS) and overall survival