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Sample records for mouse lymphoma model

  1. Genetic analysis of radiation-induced mouse thymic lymphomas

    International Nuclear Information System (INIS)

    Kominami, R.; Wakabayashi, Y.; Niwa, O.

    2003-01-01

    Mouse thymic lymphomas are one of the classic models of radiation-induced malignancies, and the model has been used for the study of genes involved in carcinogenesis. ras oncogenes are the first isolate which undergoes mutations in 10 to 30 % of lymphomas, and p16INK4a and p19ARF in the INK4a-ARF locus are also frequently inactivated. In our previous study, the inactivation of Ikaros, a key regurator of lymphoid system, was found in those lymphomas, and it was suggested that there are other responsible genes yet to be discovered. On the other hand, genetic predisposition to radiation-induced lymphoma often differs in different strains, and this reflects the presence of low penetrance genes that can modify the impact of a given mutation. Little study of such modifiers or susceptibility genes has been performed, either. Recent availability of databases on mouse genome information and the power of mouse genetic system underline usefulness of the lymphoma model in search for novel genes involved, which may provide clues to molecular mechanisms of development of the radiogenic lymphoma and also genes involved in human lymphomas and other malignancies. Accordingly, we have carried out positional cloning for the two different types of tumor-related genes. In this symposium, our current progress is presented that includes genetic mapping of susceptibility/ resistance loci on mouse chromosomes 4, 5 and 19, and also functional analysis of a novel tumor suppressor gene, Rit1/Bcl11b, that has been isolated from allelic loss (LOH) mapping and sequence analysis for γ -ray induced mouse thymic lymphomas

  2. Single-mass mutations associated with mouse lymphomas

    International Nuclear Information System (INIS)

    Guerrero, I.; Berman, J.W.; Diamond, L.E.; Newcomb, E.W.; Villasante, A.

    1986-01-01

    The authors study the induction of mouse lymphomas after treatment with a chemical carcinogen, nitrosomethyl urea (NMU), or with gamma irradiation. The koplan fractionated gamma radiation scheme and an established protocol for NMU tumor formation were chosen as protocols for induction of mouse lymphomas. In both cases, the mice developed thymic lymphomas with up to 90% incidence. In NMU induction, the latency period is shorter than irradiation

  3. PD-1/CTLA-4 Blockade Inhibits Epstein-Barr Virus-Induced Lymphoma Growth in a Cord Blood Humanized-Mouse Model.

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    Shi-Dong Ma

    2016-05-01

    Full Text Available Epstein-Barr virus (EBV infection causes B cell lymphomas in humanized mouse models and contributes to a variety of different types of human lymphomas. T cells directed against viral antigens play a critical role in controlling EBV infection, and EBV-positive lymphomas are particularly common in immunocompromised hosts. We previously showed that EBV induces B cell lymphomas with high frequency in a cord blood-humanized mouse model in which EBV-infected human cord blood is injected intraperitoneally into NOD/LtSz-scid/IL2Rγnull (NSG mice. Since our former studies showed that it is possible for T cells to control the tumors in another NSG mouse model engrafted with both human fetal CD34+ cells and human thymus and liver, here we investigated whether monoclonal antibodies that block the T cell inhibitory receptors, PD-1 and CTLA-4, enhance the ability of cord blood T cells to control the outgrowth of EBV-induced lymphomas in the cord-blood humanized mouse model. We demonstrate that EBV-infected lymphoma cells in this model express both the PD-L1 and PD-L2 inhibitory ligands for the PD-1 receptor, and that T cells express the PD-1 and CTLA-4 receptors. Furthermore, we show that the combination of CTLA-4 and PD-1 blockade strikingly reduces the size of lymphomas induced by a lytic EBV strain (M81 in this model, and that this anti-tumor effect requires T cells. PD-1/CTLA-4 blockade markedly increases EBV-specific T cell responses, and is associated with enhanced tumor infiltration by CD4+ and CD8+ T cells. In addition, PD-1/CTLA-4 blockade decreases the number of both latently, and lytically, EBV-infected B cells. These results indicate that PD-1/CTLA-4 blockade enhances the ability of cord blood T cells to control outgrowth of EBV-induced lymphomas, and suggest that PD-1/CTLA-4 blockade might be useful for treating certain EBV-induced diseases in humans.

  4. MoMuLV-ts-1: A Unique Mouse Model of Retrovirus-Induced Lymphoma Transmitted by Breast Milk

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    J. Chakraborty

    2011-01-01

    Full Text Available Our laboratory has developed a murine model of lymphoma via breast milk transmission of MoMuLV-ts-1 (Moloney murine leukemia virus-temperature sensitive mutant-1. Uninfected offspring suckled from infected surrogate mothers become infected and develop lymphoma. Multiple gene integration sites of ts-1 into the infected mouse genome including tacc3, aurka, ndel1, tpx2, p53, and rhamm were identified, and mRNA expressions were quantitated. These genes produce centrosomal proteins, which may be involved in abnormal chromosomal segregation leading to aneuploidy or multiploidy, thus causing lymphoma. Since there is no report to date on this retroviral model leading to centrosomal abnormality, and causing lymphoma development, this is a valuable and unique model to study the centrosomal involvement in lymphomagenesis.

  5. A Color-coded Imageable Syngeneic Mouse Model of Stromal-cell Recruitment by Metastatic Lymphoma.

    Science.gov (United States)

    Matsumoto, Takuro; Suetsugu, Atsushi; Shibata, Yuhei; Nakamura, Nobuhiko; Aoki, Hitomi; Kunisada, Takahiro; Tsurumi, Hisashi; Shimizu, Masahito; Hoffman, Robert M

    2015-09-01

    A syngeneic color-coded imageable lymphoma model has been developed to visualize recruitment of host stromal cells by malignant lymphoma during metastasis. The EL4 cell line was previously derived from a lymphoma induced in a C57/BL6 mouse by 9,10-dimethyl-1,2-benzanthracene. EL4 lymphoma cells expressing red fluorescent protein (EL4-RFP) were initially established. EL4-RFP cells were subsequently injected into the tail vein of C57/BL6-GFP transgenic mice. EL4-RFP metastasis was observed in the lymph nodes of the upper mediastinum and in the liver 28 days after cell injection. Large EL4-RFP liver metastases in C57/BL6-GFP mice contained GFP-expressing stromal cells derived from the host. In addition, EL4-RFP lymphoma metastasis was formed in peri-gastric lymph nodes, which were also enriched in host GFP-expressing cells. Furthermore, EL4-RFP lymphoma cells were also observed in the peripheral blood and bone marrow of C57/BL6-GFP transgenic mice, where they were associated with GFP-expressing host cells. Lymph node, liver and bone marrow metastases were found approximately 4 weeks after transplantation and all RFP-expressing metastases were highly enriched in GFP-expressing host stromal cells. This model of malignant lymphoma can be used to study early tumor development, metastasis, and the role of the stroma, as well as for discovery and evaluation of novel therapeutics for this treatment-resistant disease. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  6. Radiation carcinogenesis in mouse thymic lymphomas

    International Nuclear Information System (INIS)

    Kominami, Ryo; Niwa, Ohtsura

    2006-01-01

    Ionizing radiation is a well-known carcinogen for various human tissues and a complete carcinogen that is able to initiate and promote neoplastic progression. Studies of radiation-induced mouse thymic lymphomas, one of the classic models in radiation carcinogenesis, demonstrated that even the unirradiated thymus is capable of developing into full malignancy when transplanted into the kidney capsule or subcutaneous tissue of irradiated mice. This suggests that radiation targets tissues other than thymocytes to allow expansion of cells with tumorigenic potential in the thymus. The idea is regarded as the ''indirect mechanism'' for tumor development. This paper reviews the indirect mechanism and genes affecting the development of thymic lymphomas that we have analyzed. One is the Bcl11b/Rit1 tumor suppressor gene and the other is Mtf-1 gene affecting tumor susceptibility. (author)

  7. Longitudinal Multiplexed Measurement of Quantitative Proteomic Signatures in Mouse Lymphoma Models Using Magneto-Nanosensors.

    Science.gov (United States)

    Lee, Jung-Rok; Appelmann, Iris; Miething, Cornelius; Shultz, Tyler O; Ruderman, Daniel; Kim, Dokyoon; Mallick, Parag; Lowe, Scott W; Wang, Shan X

    2018-01-01

    Cancer proteomics is the manifestation of relevant biological processes in cancer development. Thus, it reflects the activities of tumor cells, host-tumor interactions, and systemic responses to cancer therapy. To understand the causal effects of tumorigenesis or therapeutic intervention, longitudinal studies are greatly needed. However, most of the conventional mouse experiments are unlikely to accommodate frequent collection of serum samples with a large enough volume for multiple protein assays towards single-object analysis. Here, we present a technique based on magneto-nanosensors to longitudinally monitor the protein profiles in individual mice of lymphoma models using a small volume of a sample for multiplex assays. Methods: Drug-sensitive and -resistant cancer cell lines were used to develop the mouse models that render different outcomes upon the drug treatment. Two groups of mice were inoculated with each cell line, and treated with either cyclophosphamide or vehicle solution. Serum samples taken longitudinally from each mouse in the groups were measured with 6-plex magneto-nanosensor cytokine assays. To find the origin of IL-6, experiments were performed using IL-6 knock-out mice. Results: The differences in serum IL-6 and GCSF levels between the drug-treated and untreated groups were revealed by the magneto-nanosensor measurement on individual mice. Using the multiplex assays and mouse models, we found that IL-6 is secreted by the host in the presence of tumor cells upon the drug treatment. Conclusion: The multiplex magneto-nanosensor assays enable longitudinal proteomic studies on mouse tumor models to understand tumor development and therapy mechanisms more precisely within a single biological object.

  8. Studies on a transplantable C57BL/6 mouse lymphoma

    International Nuclear Information System (INIS)

    Kendall, C.E.

    1977-01-01

    A C57BL/6 mouse lymphoma was demonstrated to be of T cell origin by treating the lymphoma cells with anti-Thy 1.2 antisera in a complement-dependent cytotoxicity test. The lymphoma's growth pattern was described using flow microfluorometric determinations and spleen weight progression. C-type particles were identified in electron micrographs of the lymphoma. C57BL/6 mice were immunized against the lymphoma by injecting x-ray inactivated lymphoma cells into the mice. Protection of immunized mice against live lymphoma cells demonstrated tumor antigens on the lymphoma cells. The success of immunization was found to depend on: route of injection, antigen dosage, state of the antigen, number of injections and the vaccination-challenge interval. Attempts were made to passively transfer immunity from immunized C57BL/6 mice which had survived lymphoma challenge to non-treated, syngeneic mice. The route of immunization in the donors influenced the success of passively transferred immunity in the recipients. Serum from days 1 to 3 and days 11 to death (day 17) had an enhancing effect on lymphoma growth. However, sera from days 5 to 9 retarded lymphoma growth. The C57BL/6 lymphoma cells were injected into rabbits and other strains of mice to demonstrate tumor specificity. The lymphoma did not grow in rabbits and only grew in one mouse strain. This strain had the same major histocompatibility loci as C57BL/6 mice. Crosses were made between C57BL/6 mice and a resistant strain of mice (DBA/2 mice). The F 1 hybrids were found to be less susceptible to the lymphoma than the C57BL/6 strain. Sublethal x-irradiation of the F 1 mice decreased its ability to resist the C57BL/6 lymphoma. Immunization with x-ray inactivated C57BL/6 lymphoma cells increased survival after challenge with lymphoma in the F 1 mice

  9. Piperlongumine inhibits LMP1/MYC-dependent mouse B-lymphoma cells

    International Nuclear Information System (INIS)

    Han, Seong-Su; Tompkins, Van S.; Son, Dong-Ju; Kamberos, Natalie L.; Stunz, Laura L.; Halwani, Ahmad; Bishop, Gail A.; Janz, Siegfried

    2013-01-01

    Highlights: •Mouse model of human Burkitt lymphoma revealed cancer inhibition by PL. •Treatment with PL led to apoptosis of malignant but not normal B cells. •PL inhibited LMP1–NF-κB–Myc-dependent target genes including p21-encoding Cdkn1a. •PL holds promise for new interventions approaches to hematologic malignancies. -- Abstract: Piperlongumine (PL), isolated from the fruit of Long pepper, Piper longum, is a cancer-inhibiting compound that selectively kills tumor cells while sparing their normal counterparts. Here we evaluated the efficacy with which PL suppresses malignant B cells derived from a newly developed, double-transgenic mouse model of human endemic Burkitt lymphoma (BL), designated mCD40-LMP1/iMyc Eμ . PL inhibited tumor cell proliferation in a concentration-dependent manner and induced apoptosis of neoplastic but not normal B cells. Treatment with PL resulted in downregulation of EBV-encoded LMP1, cellular Myc, constitutive NF-κB activity, and a host of LMP1-Myc-NF-κB-regulated target genes including Aurka, Bcat1, Bub1b, Ccnb1, Chek1, Fancd2, Tfrc and Xrcc6. Of note, p21 Cip1 -encoding Cdkn1a was suppressed independent of changes in Trp53 mRNA levels and p53 DNA-binding activity. Considering the central role of the LMP1–NF-κB–Myc axis in B-lineage neoplasia, these findings further our understanding of the mechanisms by which PL inhibits B-lymphoma and provide a preclinical rationale for the inclusion of PL in new interventions in blood cancers

  10. Piperlongumine inhibits LMP1/MYC-dependent mouse B-lymphoma cells

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    Han, Seong-Su; Tompkins, Van S. [Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA (United States); Son, Dong-Ju [Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (United States); Kamberos, Natalie L. [Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA (United States); Stunz, Laura L. [Deparment of Microbiology, University of Iowa Carver College of Medicine, Iowa City, IA (United States); Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA (United States); Iowa City VAMC, Iowa City, IA (United States); Halwani, Ahmad [Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA (United States); Bishop, Gail A. [Deparment of Microbiology, University of Iowa Carver College of Medicine, Iowa City, IA (United States); Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA (United States); Iowa City VAMC, Iowa City, IA (United States); Janz, Siegfried, E-mail: siegfried-janz@uiowa.edu [Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA (United States)

    2013-07-12

    Highlights: •Mouse model of human Burkitt lymphoma revealed cancer inhibition by PL. •Treatment with PL led to apoptosis of malignant but not normal B cells. •PL inhibited LMP1–NF-κB–Myc-dependent target genes including p21-encoding Cdkn1a. •PL holds promise for new interventions approaches to hematologic malignancies. -- Abstract: Piperlongumine (PL), isolated from the fruit of Long pepper, Piper longum, is a cancer-inhibiting compound that selectively kills tumor cells while sparing their normal counterparts. Here we evaluated the efficacy with which PL suppresses malignant B cells derived from a newly developed, double-transgenic mouse model of human endemic Burkitt lymphoma (BL), designated mCD40-LMP1/iMyc{sup Eμ}. PL inhibited tumor cell proliferation in a concentration-dependent manner and induced apoptosis of neoplastic but not normal B cells. Treatment with PL resulted in downregulation of EBV-encoded LMP1, cellular Myc, constitutive NF-κB activity, and a host of LMP1-Myc-NF-κB-regulated target genes including Aurka, Bcat1, Bub1b, Ccnb1, Chek1, Fancd2, Tfrc and Xrcc6. Of note, p21{sup Cip1}-encoding Cdkn1a was suppressed independent of changes in Trp53 mRNA levels and p53 DNA-binding activity. Considering the central role of the LMP1–NF-κB–Myc axis in B-lineage neoplasia, these findings further our understanding of the mechanisms by which PL inhibits B-lymphoma and provide a preclinical rationale for the inclusion of PL in new interventions in blood cancers.

  11. A Rapid Embryonic Stem Cell-Based Mouse Model for B-cell Lymphomas Driven by Epstein-Barr Virus Protein LMP1.

    Science.gov (United States)

    Ba, Zhaoqing; Meng, Fei-Long; Gostissa, Monica; Huang, Pei-Yi; Ke, Qiang; Wang, Zhe; Dao, Mai N; Fujiwara, Yuko; Rajewsky, Klaus; Zhang, Baochun; Alt, Frederick W

    2015-06-01

    The Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) contributes to oncogenic human B-cell transformation. Mouse B cells conditionally expressing LMP1 are not predisposed to B-cell malignancies, as LMP1-expressing B cells are eliminated by T cells. However, mice with conditional B-cell LMP1 expression and genetic elimination of α/β and γ/δ T cells ("CLT" mice) die early in association with B-cell lymphoproliferation and lymphomagenesis. Generation of CLT mice involves in-breeding multiple independently segregating alleles. Thus, although introduction of additional activating or knockout mutations into the CLT model is desirable for further B-cell expansion and immunosurveillance studies, doing such experiments by germline breeding is time-consuming, expensive, and sometimes unfeasible. To generate a more tractable model, we generated clonal CLT embryonic stem (ES) cells from CLT embryos and injected them into RAG2-deficient blastocysts to generate chimeric mice, which, like germline CLT mice, harbor splenic CLT B cells and lack T cells. CLT chimeric mice generated by this RAG2-deficient blastocyst complementation ("RDBC") approach die rapidly in association with B-cell lymphoproliferation and lymphoma. Because CLT lymphomas routinely express the activation-induced cytidine deaminase (AID) antibody diversifier, we tested potential AID roles by eliminating the AID gene in CLT ES cells and testing them via RDBC. We found that CLT and AID-deficient CLT ES chimeras had indistinguishable phenotypes, showing that AID is not essential for LMP1-induced lymphomagenesis. Beyond expanding accessibility and utility of CLT mice as a cancer immunotherapy model, our studies provide a new approach for facilitating generation of genetically complex mouse cancer models. ©2015 American Association for Cancer Research.

  12. NKT Cell Responses to B Cell Lymphoma.

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    Li, Junxin; Sun, Wenji; Subrahmanyam, Priyanka B; Page, Carly; Younger, Kenisha M; Tiper, Irina V; Frieman, Matthew; Kimball, Amy S; Webb, Tonya J

    2014-06-01

    Natural killer T (NKT) cells are a unique subset of CD1d-restricted T lymphocytes that express characteristics of both T cells and natural killer cells. NKT cells mediate tumor immune-surveillance; however, NKT cells are numerically reduced and functionally impaired in lymphoma patients. Many hematologic malignancies express CD1d molecules and co-stimulatory proteins needed to induce anti-tumor immunity by NKT cells, yet most tumors are poorly immunogenic. In this study, we sought to investigate NKT cell responses to B cell lymphoma. In the presence of exogenous antigen, both mouse and human NKT cell lines produce cytokines following stimulation by B cell lymphoma lines. NKT cell populations were examined ex vivo in mouse models of spontaneous B cell lymphoma, and it was found that during early stages, NKT cell responses were enhanced in lymphoma-bearing animals compared to disease-free animals. In contrast, in lymphoma-bearing animals with splenomegaly and lymphadenopathy, NKT cells were functionally impaired. In a mouse model of blastoid variant mantle cell lymphoma, treatment of tumor-bearing mice with a potent NKT cell agonist, α-galactosylceramide (α-GalCer), resulted in a significant decrease in disease pathology. Ex vivo studies demonstrated that NKT cells from α-GalCer treated mice produced IFN-γ following α-GalCer restimulation, unlike NKT cells from vehicle-control treated mice. These data demonstrate an important role for NKT cells in the immune response to an aggressive hematologic malignancy like mantle cell lymphoma.

  13. Genotoxic effects of synthetic amorphous silica nanoparticles in the mouse lymphoma assay

    Directory of Open Access Journals (Sweden)

    Eşref Demir

    Full Text Available Synthetic amorphous silica nanoparticles (SAS NPs have been used in various industries, such as plastics, glass, paints, electronics, synthetic rubber, in pharmaceutical drug tablets, and a as food additive in many processed foods. There are few studies in the literature on NPs using gene mutation approaches in mammalian cells, which represents an important gap for genotoxic risk estimations. To fill this gap, the mouse lymphoma L5178Y/Tk+/− assay (MLA was used to evaluate the mutagenic effect for five different concentrations (from 0.01 to 150 μg/mL of two different sizes of SAS NPs (7.172 and 7.652 nm and a fine collodial form of silicon dioxide (SiO2. This assay detects a broad spectrum of mutational events, from point mutations to chromosome alterations. The results obtained indicate that the two selected SAS NPs are mutagenic in the MLA assay, showing a concentration-dependent effect. The relative mutagenic potencies according to the induced mutant frequency (IMF are as follows: SAS NPs (7.172 nm (IMF = 705.5 × 10−6, SAS NPs (7.652 nm (IMF = 575.5 × 10−6, and SiO2 (IMF = 57.5 × 10−6. These in vitro results, obtained from mouse lymphoma cells, support the genotoxic potential of NPs as well as focus the discussion of the benefits/risks associated with their use in different areas. Keywords: Synthetic amorphous silica nanoparticles, Mouse lymphoma assay, Mutagenic agents, Thymidine kinase (Tk gene, In vitro mutagenicity

  14. Moesin Is a Biomarker for the Assessment of Genotoxic Carcinogens in Mouse Lymphoma

    Science.gov (United States)

    Lee, Yoen Jung; Choi, In-Kwon; Sheen, Yhun Yhong; Park, Sue Nie; Kwon, Ho Jeong

    2012-01-01

    1,2-Dibromoethane and glycidol are well known genotoxic carcinogens, which have been widely used in industry. To identify a specific biomarker for these carcinogens in cells, the cellular proteome of L5178Y mouse lymphoma cells treated with these compounds was analyzed by 2-dimensional gel electrophoresis (2-DE) and MALDI-TOF mass spectrometry (MS). Of 50 protein spots showing a greater than 1.5-fold increase or decrease in intensity compared to control cells on a 2-D gel, we focused on the candidate biomarker moesin. Western analysis using monoclonal rabbit anti-moesin confirmed the identity of the protein and its increased level of expression upon exposure to the carcinogenic compounds. Moesin expression also increased in cells treated with six additional genotoxic carcinogens, verifying that moesin could serve as a biomarker to monitor phenotypic change upon exposure to genotoxic carcinogens in L5178Y mouse lymphoma cells. PMID:22358511

  15. A novel xenograft model of cutaneous T-cell lymphoma

    DEFF Research Database (Denmark)

    Krejsgaard, Thorbjørn; Kopp, Katharina; Ralfkiaer, Elisabeth

    2010-01-01

    Cutaneous T-cell lymphomas (CTCLs) are characterized by accumulation of malignant T cells in the skin. Early disease resembles benign skin disorders but during disease progression cutaneous tumors develop, and eventually the malignant T cells can spread to lymph nodes and internal organs. However...... and lymphatic tumors, originated from the transplanted malignant T cells. In conclusion, we describe a novel mouse model of tumor stage CTCL for future studies of disease dissemination and preclinical evaluations of new therapeutic strategies....

  16. Hepatitis C Virus-Related Lymphomagenesis in a Mouse Model

    Science.gov (United States)

    Tsukiyama-Kohara, Kyoko; Sekiguchi, Satoshi; Kasama, Yuri; Salem, Nagla Elwy; Machida, Keigo; Kohara, Michinori

    2011-01-01

    B cell non-Hodgkin lymphoma is a typical extrahepatic manifestation frequently associated with hepatitis C virus (HCV) infection. The mechanism by which HCV infection leads to lymphoproliferative disorder remains unclear. Our group established HCV transgenic mice that expressed the full HCV genome in B cells (RzCD19Cre mice). We observed a 25.0% incidence of diffuse large B cell non-Hodgkin lymphomas (22.2% in male and 29.6% in female mice) within 600 days of birth. Interestingly, RzCD19Cre mice with substantially elevated serum-soluble interleukin-2 receptor α-subunit (sIL-2Rα) levels (>1000 pg/mL) developed B cell lymphomas. Another mouse model of lymphoproliferative disorder was established by persistent expression of HCV structural proteins through disruption of interferon regulatory factor-1 (irf-1_/_/CN2 mice). Irf-1_/_/CN2 mice showed extremely high incidences of lymphomas and lymphoproliferative disorders. Moreover, these mice showed increased levels of interleukin (IL)-2, IL-10, and Bcl-2 as well as increased Bcl-2 expression, which promoted oncogenic transformation of lymphocytes. PMID:22084693

  17. Molecular Cytogenetic Characterization Identified the Murine B-Cell Lymphoma Cell Line A-20 as a Model for Sporadic Burkitt's Lymphoma.

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    Guja, Karolina; Liehr, Thomas; Rincic, Martina; Kosyakova, Nadezda; Hussein Azawi, Shaymaa S

    2017-11-01

    Here, we report the first molecular cytogenetic characterization of the BALB/cAnN mouse derived B-cell non-Hodgkin lymphoma (B-cell NHL) cell lines A-20. Even though previously used as a model for testing of, for example, dexametason, up to present, no data in the genetic properties of A-20 were available. The present study closed this gap and provides evidence that A-20 is a model for B-cell NHL subgroup sporadic Burkitt's lymphoma. C-myc oncogene is involved in a translocation and copy number alterations as gain of murine 14q material could be observed. Interestingly, the cell line showed the karyotype 39,X,-X or -Y,t(2;15)(qE5;qD2),del(6)(qB3qC3),del(9)(qA3qA4),dup(14)(qE1qE4) in ~95% of the cells, being exceptionally stable for cell lines being established 38 years ago. Still, ~5% of the cells showed polyploidization followed by chromothripsis. It remains to be determined if this can be observed also in other cell lines, just has not been reported yet, and/or if it is a unique feature of A-20. Overall, finally here, the necessary genetic data to identify A-20 as a model for human sporadic Burkitt's lymphoma are provided.

  18. Sequential mutations in Notch1, Fbxw7, and Tp53 in radiation-induced mouse thymic lymphomas.

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    Jen, Kuang-Yu; Song, Ihn Young; Banta, Karl Luke; Wu, Di; Mao, Jian-Hua; Balmain, Allan

    2012-01-19

    T-cell acute lymphoblastic lymphomas commonly demonstrate activating Notch1 mutations as well as mutations or deletions in Fbxw7. However, because Fbxw7 targets Notch1 for degradation, genetic alterations in these genes are expected to be mutually exclusive events in lymphomagenesis. Previously, by using a radiation-induced Tp53-deficient mouse model for T-cell acute lymphoblastic lymphoma, we reported that loss of heterozygosity at the Fbxw7 locus occurs frequently in a Tp53-dependent manner. In the current study, we show that these thymic lymphomas also commonly exhibit activating Notch1 mutations in the proline-glutamic acid-serine-threonine (PEST) domain. Moreover, concurrent activating Notch1 PEST domain mutations and single-copy deletions at the Fbxw7 locus occur with high frequency in the same individual tumors, indicating that these changes are not mutually exclusive events. We further demonstrate that although Notch1 PEST domain mutations are independent of Tp53 status, they are completely abolished in mice with germline Fbxw7 haploinsufficiency. Therefore, Notch1 PEST domain mutations only occur when Fbxw7 expression levels are intact. These data suggest a temporal sequence of mutational events involving these important cancer-related genes, with Notch1 PEST domain mutations occurring first, followed by Fbxw7 deletion, and eventually by complete loss of Tp53.

  19. Characterization of mitomycin-C-sensitive mouse lymphoma L5178Y cell mutants

    International Nuclear Information System (INIS)

    Inaba, Hiroko; Shiomi, Naoko; Shiomi, Tadahiro; Sato, Koki; Yoshida, Michihiro.

    1985-01-01

    Twenty-six mutants showing high sensitivity to mytomicin-C (MMC) were isolated from mouse lymphoma L5178Y cells by a replica-plating technique. Twenty-five of the mutants were 5 - 10 times more sensitive to MMC than were parental cells, and showed normal sensitivity to U.V. light and x-rays. From a complementation analysis, 5 mutants (MC s ) isolated from independently mutagenized cell populations were classified into two groups. These mutants possessed recessive character for MMC-sensitivity and there were at least two genes involved in the MMC-sensitivity. As for DNA-damaging factors, such as photoadducts of 8-methoxypsoralen (8-MOP) and 3-carbethoxysoralen (3-CPs), MC s mutants showed higher sensitivity to photoadducts of 8-MOP than to (3-CPs). MC s mutants were also highly sensitive to a DNA cross-linking agent, cisplatin. Characterization of the sensitivity of mouse MC s mutants was analogous to that of Fanconi's anemia (FA)-derived cells. Low concentrations (10 ng/ml) of MMC induced chromosome aberration in a high incidence in mouse MC s cells, as well as in FA cells. The frequency of MMC-induced chromosome aberrations was normal in hybrid cells between normal human diploid somatic cells and mouse mutants and between FA cells and mouse wild cells, and hereditary deficiency became normal by hybrization. (Namekawa, K.)

  20. From Immunodeficiency to Humanization: The Contribution of Mouse Models to Explore HTLV-1 Leukemogenesis

    Directory of Open Access Journals (Sweden)

    Eléonore Pérès

    2015-12-01

    Full Text Available The first discovered human retrovirus, Human T-Lymphotropic Virus type 1 (HTLV-1, is responsible for an aggressive form of T cell leukemia/lymphoma. Mouse models recapitulating the leukemogenesis process have been helpful for understanding the mechanisms underlying the pathogenesis of this retroviral-induced disease. This review will focus on the recent advances in the generation of immunodeficient and human hemato-lymphoid system mice with a particular emphasis on the development of mouse models for HTLV-1-mediated pathogenesis, their present limitations and the challenges yet to be addressed.

  1. ONC201 induces cell death in pediatric non-Hodgkin's lymphoma cells

    OpenAIRE

    Talekar, Mala K; Allen, Joshua E; Dicker, David T; El-Deiry, Wafik S

    2015-01-01

    ONC201/TIC10 is a small molecule initially discovered by its ability to coordinately induce and activate the TRAIL pathway selectively in tumor cells and has recently entered clinical trials in adult advanced cancers. The anti-tumor activity of ONC201 has previously been demonstrated in several preclinical models of cancer, including refractory solid tumors and a transgenic lymphoma mouse model. Based on the need for new safe and effective therapies in pediatric non-Hodgkin's lymphoma (NHL) a...

  2. Chromosomal aberrations induced by X-rays in two mouse lymphoma (L5178Y) sublines of different radiosensitivity

    International Nuclear Information System (INIS)

    Bocian, E.; Bouzyk, E.; Rosiek, O.; Ziemba-Zoltowska, B.

    1982-01-01

    Two mouse lymphoma cell strains, L5178-S and L5178-R, were pulse labelled for 20 min with tritiated thymidine, and then irradiated with 1 Gy of X-rays (180 kV at 0.34 Gy/min). It was found that the cells of the radiation-sensitive subline (S) displayed a higher frequency of chromatid aberrations following radiation exposure, than cells of the radiation-resistant subline (R). (U.K.)

  3. Chromosomal aberrations induced by X-rays in two mouse lymphoma (L5178Y) sublines of different radiosensitivity

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    Bocian, E.; Bouzyk, E.; Rosiek, O.; Ziemba-Zoltowska, B. (Institute of Nuclear Research, Warsaw (Poland))

    1982-09-01

    Two mouse lymphoma cell strains, L5178-S and L5178-R, were pulse labelled for 20 min with tritiated thymidine, and then irradiated with 1 Gy of X-rays (180 kV at 0.34 Gy/min). It was found that the cells of the radiation-sensitive subline (S) displayed a higher frequency of chromatid aberrations following radiation exposure, than cells of the radiation-resistant subline (R).

  4. Prevention of EBV lymphoma development by oncolytic myxoma virus in a murine xenograft model of post-transplant lymphoproliferative disease

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    Kim, Manbok, E-mail: manbok66@dankook.ac.kr [Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610 (United States); Rahman, Masmudur M. [Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610 (United States); Cogle, Christopher R. [Department of Hematology/Oncology, University of Florida, Gainesville, FL 32610 (United States); McFadden, Grant [Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610 (United States)

    2015-07-10

    Epstein–Barr virus (EBV) has been associated with a variety of epithelial and hematologic malignancies, including B-, T- and NK cell-lymphomas, Hodgkin's disease (HD), post-transplant lymphoproliferative diseases (LPDs), nasopharyngeal and gastric carcinomas, smooth muscle tumors, and HIV-associated lymphomas. Currently, treatment options for EBV-associated malignancies are limited. We have previously shown that myxoma virus specifically targets various human solid tumors and leukemia cells in a variety of animal models, while sparing normal human or murine tissues. Since transplant recipients of bone marrow or solid organs often develop EBV-associated post-transplant LPDs and lymphoma, myxoma virus may be of utility to prevent EBV-associated malignancies in immunocompromised transplant patients where treatment options are frequently limited. In this report, we demonstrate the safety and efficacy of myxoma virus purging as a prophylactic strategy for preventing post-transplant EBV-transformed human lymphomas, using a highly immunosuppressed mouse xenotransplantation model. This provides support for developing myxoma virus as a potential oncolytic therapy for preventing EBV-associated LPDs following transplantation of bone marrow or solid organ allografts. - Highlights: • Myxoma virus effectively infects and purges EBV lymphoma cells in vivo. • Oncolytic myxoma virus effectively eradicates oncogenic EBV tumorigenesis. • Ex vivo pre-treatment of myxoma virus can be effective as a preventive treatment modality for post-transplant lymphoproliferative diseases.

  5. Prevention of EBV lymphoma development by oncolytic myxoma virus in a murine xenograft model of post-transplant lymphoproliferative disease

    International Nuclear Information System (INIS)

    Kim, Manbok; Rahman, Masmudur M.; Cogle, Christopher R.; McFadden, Grant

    2015-01-01

    Epstein–Barr virus (EBV) has been associated with a variety of epithelial and hematologic malignancies, including B-, T- and NK cell-lymphomas, Hodgkin's disease (HD), post-transplant lymphoproliferative diseases (LPDs), nasopharyngeal and gastric carcinomas, smooth muscle tumors, and HIV-associated lymphomas. Currently, treatment options for EBV-associated malignancies are limited. We have previously shown that myxoma virus specifically targets various human solid tumors and leukemia cells in a variety of animal models, while sparing normal human or murine tissues. Since transplant recipients of bone marrow or solid organs often develop EBV-associated post-transplant LPDs and lymphoma, myxoma virus may be of utility to prevent EBV-associated malignancies in immunocompromised transplant patients where treatment options are frequently limited. In this report, we demonstrate the safety and efficacy of myxoma virus purging as a prophylactic strategy for preventing post-transplant EBV-transformed human lymphomas, using a highly immunosuppressed mouse xenotransplantation model. This provides support for developing myxoma virus as a potential oncolytic therapy for preventing EBV-associated LPDs following transplantation of bone marrow or solid organ allografts. - Highlights: • Myxoma virus effectively infects and purges EBV lymphoma cells in vivo. • Oncolytic myxoma virus effectively eradicates oncogenic EBV tumorigenesis. • Ex vivo pre-treatment of myxoma virus can be effective as a preventive treatment modality for post-transplant lymphoproliferative diseases

  6. The relationship between cell killing, chromosome aberrations, spindle defects, and mitotic delay in mouse lymphoma cells of differential sensitivity to X-rays

    International Nuclear Information System (INIS)

    Scott, D.; Zampetti-Bosseler, F.

    1980-01-01

    A study has been made of the effects of x radiation on an ultrasensitive subline of L5178Y mouse lymphoma cells. It has been shown that at survival levels above about 20 per cent, chromosome structural aberrations which lead to bridges and fragments at anaphase are about four times more frequent than spindle defects. The results demonstrated the higher frequency of structural aberrations and spindle defects, and the greater mitotic delay in the X-ray-sensitive than in the X-ray-resistant cell line. A model is proposed which causally relates these end-points to cell killing and DNA repair. (author)

  7. [Establishment and identification of mouse lymphoma cell line EL4 expressing red fluorescent protein].

    Science.gov (United States)

    Li, Yan-Jie; Cao, Jiang; Chen, Chong; Wang, Dong-Yang; Zeng, Ling-Yu; Pan, Xiu-Ying; Xu, Kai-Lin

    2010-02-01

    This study was purposed to construct a lentiviral vector encoding red fluorescent protein (DsRed) and transfect DsRed into EL4 cells for establishing mouse leukemia/lymphoma model expressing DsRed. The bicistronic SIN lentiviral transfer plasmid containing the genes encoding neo and internal ribosomal entry site-red fluorescent protein (IRES-DsRed) was constructed. Human embryonic kidney 293FT cells were co-transfected with the three plasmids by liposome method. The viral particles were collected and used to transfect EL4 cells, then the cells were selected by G418. The results showed that the plasmid pXZ208-neo-IRES-DsRed was constructed successfully, and the viral titer reached to 10(6) U/ml. EL4 cells were transfected by the viral solution efficiently. The transfected EL4 cells expressing DsRed survived in the final concentration 600 microg/ml of G418. The expression of DsRed in the transfected EL4 cells was demonstrated by fluorescence microscopy and flow cytometry. In conclusion, the EL4/DsRed cell line was established successfully.

  8. Regulation of radiation-induced protein kinase Cδ activation in radiation-induced apoptosis differs between radiosensitive and radioresistant mouse thymic lymphoma cell lines

    International Nuclear Information System (INIS)

    Nakajima, Tetsuo; Yukawa, Osami; Tsuji, Hideo; Ohyama, Harumi; Wang, Bing; Tatsumi, Kouichi; Hayata, Isamu; Hama-Inaba, Hiroko

    2006-01-01

    Protein kinase Cδ (PKCδ) has an important role in radiation-induced apoptosis. The expression and function of PKCδ in radiation-induced apoptosis were assessed in a radiation-sensitive mouse thymic lymphoma cell line, 3SBH5, and its radioresistant variant, XR223. Rottlerin, a PKCδ-specific inhibitor, completely abolished radiation-induced apoptosis in 3SBH5. Radiation-induced PKCδ activation correlated with the degradation of PKCδ, indicating that PKCδ activation through degradation is involved in radiation-induced apoptosis in radiosensitive 3SBH5. In radioresistant XR223, radiation-induced PKCδ activation was lower than that in radiosensitive 3SBH5. Cytosol PKCδ levels in 3SBH5 decreased markedly after irradiation, while those in XR223 did not. There was no apparent change after irradiation in the membrane fractions of either cell type. In addition, basal cytosol PKCδ levels in XR223 were higher than those in 3SBH5. These results suggest that the radioresistance in XR223 to radiation-induced apoptosis is due to a difference in the regulation of radiation-induced PKCδ activation compared to that of 3SBH5. On the other hand, Atm -/- mouse thymic lymphoma cells were more radioresistant to radiation-induced apoptosis than wild-type mouse thymic lymphoma cells. Irradiated wild-type cells, but not Atm -/- cells, had decreased PKCδ levels, indicating that the Atm protein is involved in radiation-induced apoptosis through the induction of PKCδ degradation. The decreased Atm protein levels induced by treatment with Atm small interfering RNA had no effect on radiation-induced apoptosis in 3SBH5 cells. These results suggest that the regulation of radiation-induced PKCδ activation, which is distinct from the Atm-mediated cascade, determines radiation sensitivity in radiosensitive 3SBH5 cells

  9. Genetic Recombination Between Stromal and Cancer Cells Results in Highly Malignant Cells Identified by Color-Coded Imaging in a Mouse Lymphoma Model.

    Science.gov (United States)

    Nakamura, Miki; Suetsugu, Atsushi; Hasegawa, Kousuke; Matsumoto, Takuro; Aoki, Hitomi; Kunisada, Takahiro; Shimizu, Masahito; Saji, Shigetoyo; Moriwaki, Hisataka; Hoffman, Robert M

    2017-12-01

    The tumor microenvironment (TME) promotes tumor growth and metastasis. We previously established the color-coded EL4 lymphoma TME model with red fluorescent protein (RFP) expressing EL4 implanted in transgenic C57BL/6 green fluorescent protein (GFP) mice. Color-coded imaging of the lymphoma TME suggested an important role of stromal cells in lymphoma progression and metastasis. In the present study, we used color-coded imaging of RFP-lymphoma cells and GFP stromal cells to identify yellow-fluorescent genetically recombinant cells appearing only during metastasis. The EL4-RFP lymphoma cells were injected subcutaneously in C57BL/6-GFP transgenic mice and formed subcutaneous tumors 14 days after cell transplantation. The subcutaneous tumors were harvested and transplanted to the abdominal cavity of nude mice. Metastases to the liver, perigastric lymph node, ascites, bone marrow, and primary tumor were imaged. In addition to EL4-RFP cells and GFP-host cells, genetically recombinant yellow-fluorescent cells, were observed only in the ascites and bone marrow. These results indicate genetic exchange between the stromal and cancer cells. Possible mechanisms of genetic exchange are discussed as well as its ramifications for metastasis. J. Cell. Biochem. 118: 4216-4221, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  10. [Establishment of EL4 tumor-bearing mouse models and investigation on immunological mechanisms of anti-tumor effect of melphalan].

    Science.gov (United States)

    Li, Mo-lin; Li, Chuan-gang; Shu, Xiao-hong; Jia, Yu-jie; Qin, Zhi-hai

    2006-03-01

    To establish mouse lymphoma EL4 tumor-bearing mouse models in wild type C57BL/6 mice and nude C57BL/6 mice respectively, and to further investigate the immunological mechanisms of anti-tumor effect of melphalan. Mouse lymphoma EL4 cells were inoculated subcutaneously into wild type C57BL/6 mice (immune-competent mice). Twelve days later, melphalan of different doses were administered intraperitoneally to treat these wild type C57BL/6 tuomr-bearing mice. Tumor sizes were observed and recorded subsequently to find out the minimal dose of melphalan that could cure the tuomr-bearing mice. Then the same amount of EL4 tumor cells were inoculated subcutaneously into wild type C57BL/6 mice and nude C57BL/6 mice (T cell-deficient mice) simultaneously, which had the same genetic background of C57BL/6. Twelve days later, melphalan of the minimal dose was given intraperitoneally to treat both the wild type and nude C57BL/6 tuomr-bearing mice. Tumor sizes were observed and recorded in these two different types of mice subsequently. A single dose of melphalan (7.5 mg/kg) could cure EL4 tumor-bearing wild type C57BL/6 mice, but could not induce tumor regression in EL4 tumor-bearing nude C57BL/6 mice. A single dose of melphalan has obvious anti-tumor effect on mouse lymphoma EL4 tumor-bearing wild type C57BL/6mice, which requires the involvement of T lymphocytes in the host probably related to their killing functions.

  11. Non-invasive bioluminescence imaging to monitor the immunological control of a plasmablastic lymphoma-like B cell neoplasia after hematopoietic cell transplantation.

    Directory of Open Access Journals (Sweden)

    Martin Chopra

    Full Text Available To promote cancer research and to develop innovative therapies, refined pre-clinical mouse tumor models that mimic the actual disease in humans are of dire need. A number of neoplasms along the B cell lineage are commonly initiated by a translocation recombining c-myc with the immunoglobulin heavy-chain gene locus. The translocation is modeled in the C.129S1-Igha(tm1(MycJanz/J mouse which has been previously engineered to express c-myc under the control of the endogenous IgH promoter. This transgenic mouse exhibits B cell hyperplasia and develops diverse B cell tumors. We have isolated tumor cells from the spleen of a C.129S1-Igha(tm1(MycJanz/J mouse that spontaneously developed a plasmablastic lymphoma-like disease. These cells were cultured, transduced to express eGFP and firefly luciferase, and gave rise to a highly aggressive, transplantable B cell lymphoma cell line, termed IM380. This model bears several advantages over other models as it is genetically induced and mimics the translocation that is detectable in a number of human B cell lymphomas. The growth of the tumor cells, their dissemination, and response to treatment within immunocompetent hosts can be imaged non-invasively in vivo due to their expression of firefly luciferase. IM380 cells are radioresistant in vivo and mice with established tumors can be allogeneically transplanted to analyze graft-versus-tumor effects of transplanted T cells. Allogeneic hematopoietic stem cell transplantation of tumor-bearing mice results in prolonged survival. These traits make the IM380 model very valuable for the study of B cell lymphoma pathophysiology and for the development of innovative cancer therapies.

  12. Immunity against mouse thymus-leukemia antigen (TL) protects against development of lymphomas induced by a chemical carcinogen, N-butyl-N-nitrosourea.

    Science.gov (United States)

    Tsujimura, Kunio; Obata, Yuichi; Matsudaira, Yasue; Ozeki, Satoshi; Taguchi, Osamu; Nishida, Keiko; Okanami, Yuko; Akatsuka, Yoshiki; Kuzushima, Kiyotaka; Takahashi, Toshitada

    2004-11-01

    Mouse thymus-leukemia antigens (TL) are aberrantly expressed on T lymphomas in C57BL/6 (B6) and C3H/He (C3H) mice, while they are not expressed on normal T lymphocytes in these strains. When N-butyl-N-nitrosourea (NBU), a chemical carcinogen, was administered orally to B6 and C3H strains, lymphoma development was slower than in T3(b)-TL gene-transduced counterpart strains expressing TL ubiquitously as self-antigens, suggesting that anti-TL immunity may play a protective role. In addition, the development of lymphomas was slightly slower in C3H than in B6, which seems to be in accordance with the results of skin graft experiments indicating that both cellular and humoral immunities against TL were stronger in C3H than B6 mice. The interesting finding that B lymphomas derived from a T3(b)-TL transgenic strain (C3H background) expressing a very high level of TL were rejected in C3H, but not in H-2K(b) transgenic mice (C3H background), raises the possibility that TL-specific effector T cell populations are eliminated and/or energized to a certain extent by interacting with H-2K(b) molecules.

  13. MYC as therapeutic target in leukemia and lymphoma

    Directory of Open Access Journals (Sweden)

    Cortiguera MG

    2015-07-01

    Full Text Available Maria G Cortiguera,1 Ana Batlle-López,1,2 Marta Albajar,1,2 M Dolores Delgado,1,3 Javier León1,3 1Institute of Biomedicine and Biotechnology of Cantabria (IBBTEC, CSIC-University of Cantabria, 2Department of Hemathology, Hospital Universitario Marqués de Valdecilla, 3Department of Molecular Biology, University of Cantabria, Santander, Spain Abstract: MYC is a transcription factor that is involved in the expression of many genes. Deregulated MYC is found in about half of human tumors, being more prevalent in hematological neoplasms. Deregulation mechanisms include chromosomal translocation (particularly in lymphoma, amplification, and hyperactivation of MYC transcription. Here we review MYC involvement in the major types of leukemia and lymphoma. MYC rearrangements appear in all Burkitt lymphomas and are common in other lymphoma types, whereas in acute lymphoblastic leukemia, acute myeloid leukemia, lymphoproliferative, and myeloproferative diseases, they are less frequent. However, MYC overexpression is present in all types of hematological malignancies and often correlates with a worse prognosis. Data in leukemia-derived cells and in animal models of lymphomagenesis and leukemogenesis suggest that MYC would be a good therapeutic target. Several MYC-directed therapies have been assayed in preclinical settings and even in clinical trials. First, peptides and small molecules that interrupt the MYC–MAX interaction impair MYC-mediated tumorogenesis in several mouse models of solid tumors, although not yet in lymphoma and leukemia models. Second, there are a number of small molecules inhibiting the interaction of MYC–MAX heterodimers with DNA, still in the preclinical research phase. Third, inhibitors of MYC expression via the inhibition of BRD4 (a reader of acetylated histones have been shown to control the growth of MYC-transformed leukemia and lymphoma cells and are being used in clinic trials. Finally, we review a number of promising MYC

  14. Identification of IgH gene rearrangement and immunophenotype in an animal model of Epstein-Barr virus-associated lymphomas.

    Science.gov (United States)

    Zhang, Yang; Peng, Xueqin; Tang, Yunlian; Gan, Xiaoning; Wang, Chengkun; Xie, Lu; Xie, Xiaoli; Gan, Runliang; Wu, Yimou

    2016-10-01

    Epstein-Barr virus (EBV) is a human oncogenic herpesvirus associated with lymphoma and nasopharyngeal carcinoma. Because the susceptible hosts of EB virus are limited to human and cotton-top tamarins (Saguinus oedipus), there have been no appropriate animal models until the lymphoma model induced by EBV in human peripheral blood lymphocyte (hu-PBL)/SCID chimeric mice was reported. However, it is still controversial whether the EBV-associated lymphoma induced in hu-PBL/SCID mice is a monoclonal tumor. In this study, we transplanted normal human peripheral blood lymphocytes (hu-PBL) from six donors infected with EBV into SCID mice to construct hu-PBL/SCID chimeric mice. The induced tumors were found in the mediastinum or abdominal cavity of SCID mice. Microscopic observation exhibited tumor cells that were large and had a plasmablastic, centroblastic or immunoblastic-like appearance. Immunophenotyping assays showed the induced tumors were LCA-positive, CD20/CD79a-positive (markers of B cells), and CD3/CD45RO-negative (markers of T cells). A human-specific Alu sequence could be amplified by Alu-PCR. This confirmed that induced tumors were B-cell lymphomas originating from the transplanted human lymphocytes rather than mouse cells. EBER in situ hybridization detected positive signals in the nuclei of the tumor cells. Expression of EBV-encoded LMP1, EBNA-1, and EBNA-2 in the tumors was significantly positive. PCR-based capillary electrophoresis analysis of IgH gene rearrangement revealed a monoclonal peak and single amplification product in all six cases of induced tumors. This indicated that EBV can induce monoclonal proliferation of human B lymphocytes and promotes the development of lymphoma. J. Med. Virol. 88:1804-1813, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  15. HSP90 inhibitor 17-AAG selectively eradicates lymphoma stem cells.

    Science.gov (United States)

    Newman, Bryan; Liu, Yan; Lee, Hsiu-Fang; Sun, Duxin; Wang, Yin

    2012-09-01

    Cancer stem cells (CSC; also called tumor-initiating cells) comprise tumor cell subpopulations that preserve the properties of quiescence, self-renewal, and differentiation of normal stem cells. In addition, CSCs are therapeutically important because of their key contributions toward drug resistance. The hypoxia-inducible transcription factor HIF1α is critical for CSC maintenance in mouse lymphoma. In this study, we showed that low concentrations of the HSP90 inhibitor 17-AAG eliminate lymphoma CSCs in vitro and in vivo by disrupting the transcriptional function of HIF1α, a client protein of HSP90. 17-AAG preferentially induced apoptosis and eliminated the colony formation capacity of mouse lymphoma CSCs and human acute myeloid leukemia (AML) CSCs. However, low concentrations of 17-AAG failed to eliminate highly proliferative lymphoma and AML cells (non-CSCs), in which the AKT-GSK3 signaling pathway is constitutively active. The heat shock transcription factor HSF1 is highly expressed in non-CSCs, but it was weakly expressed in lymphoma CSCs. However, siRNA-mediated attenuation of HSF1 abrogated the colony formation ability of both lymphoma and AML CSCs. This study supports the use of 17-AAG as a CSC targeting agent and, in addition, shows that HSF1 is an important target for elimination of both CSCs and non-CSCs in cancer. ©2012 AACR.

  16. Constitutive expression of tert in thymocytes leads to increased incidence and dissemination of T-cell lymphoma in Lck-Tert mice.

    Science.gov (United States)

    Canela, Andrés; Martín-Caballero, Juan; Flores, Juana M; Blasco, María A

    2004-05-01

    Here we describe a new mouse model with constitutive expression of the catalytic subunit of telomerase (Tert) targeted to thymocytes and peripheral T cells (Lck-Tert mice). Two independent Lck-Tert mouse lines showed higher incidences of spontaneous T-cell lymphoma than the corresponding age-matched wild-type controls, indicating that constitutive expression of Tert promotes lymphoma. Interestingly, T-cell lymphomas in Lck-Tert mice were more disseminated than those in wild-type controls and affected both lymphoid and nonlymphoid tissues, while nonlymphoid tissues were never affected with lymphoma in age-matched wild-type controls. Importantly, these roles of Tert constitutive expression in promoting tumor progression and dissemination were independent of the role of telomerase in telomere length maintenance, since telomere length distributions on a single-cell basis were identical in Lck-Tert and wild-type thymocytes. Finally, Tert constitutive expression did not interfere with telomere capping in Lck-Tert primary thymocytes, although it resulted in greater chromosomal instability upon gamma irradiation in Lck-Tert primary lymphocytes than in controls, suggesting that Tert overexpression may interfere with the cellular response to DNA damage.

  17. Complicated biallelic inactivation of Pten in radiation-induced mouse thymic lymphomas

    Energy Technology Data Exchange (ETDEWEB)

    Yamaguchi, Yu [Department of Biology, Graduate School of Science, Chiba University, Yayoicho, Inage-ku, Chiba 263-8522 (Japan); Experimental Radiobiology for Children' s Health Research Group, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba 263-8555 (Japan); Takabatake, Takashi; Kakinuma, Shizuko; Amasaki, Yoshiko; Nishimura, Mayumi; Imaoka, Tatsuhiko; Yamauchi, Kazumi; Shang, Yi [Experimental Radiobiology for Children' s Health Research Group, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba 263-8555 (Japan); Miyoshi-Imamura, Tomoko [Experimental Radiobiology for Children' s Health Research Group, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba 263-8555 (Japan); Genetic Counseling Program, Graduate School of Humanities and Sciences, Ochanomizu University, 2-1-1 Otsuka, Bunkyou-ku, Tokyo 112-8610 (Japan); Nogawa, Hiroyuki [Department of Biology, Graduate School of Science, Chiba University, Yayoicho, Inage-ku, Chiba 263-8522 (Japan); Kobayashi, Yoshiro [Department of Biomolecular Science, Faculty of Science, Toho University, Miyama 2-2-1, Funabashi, Chiba 274-8510 (Japan); Shimada, Yoshiya, E-mail: y_shimad@nirsgo.jp [Experimental Radiobiology for Children' s Health Research Group, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba 263-8555 (Japan)

    2010-04-01

    Inactivation of the phosphatase and tensin homolog gene (Pten) occurs via multiple tissue-dependent mechanisms including epigenetic silencing, point mutations, insertions, and deletions. Although frequent loss of heterozygosity around the Pten locus and plausible involvement of epigenetic silencing have been reported in radiation-induced thymic lymphomas, the proportion of lymphomas with inactivated Pten and the spectrum of causal aberrations have not been extensively characterized. Here, we assessed the mode of Pten inactivation by comprehensive analysis of the expression and alteration of Pten in 23 radiation-induced thymic lymphomas developed in B6C3F1 mice. We found no evidence for methylation-associated silencing of Pten; rather, complex structural abnormalities comprised of missense and nonsense mutations, 1- and 3-bp insertions, and focal deletions were identified in 8 of 23 lymphomas (35%). Sequencing of deletion breakpoints suggested that aberrant V(D)J recombination and microhomology-mediated rearrangement were responsible for the focal deletions. Seven of the 8 lymphomas had biallelic alterations, and 4 of them did not express Pten protein. These Pten aberrations coincided with downstream Akt phosphorylation. In conclusion, we demonstrate that Pten inactivation is frequently biallelic and is caused by a variety of structural abnormalities (rather than by epigenetic silencing) and is involved in radiation-induced lymphomagenesis.

  18. Myc contribution to γ-ray induced thymic lymphomas in mice of different genetic predispositions

    International Nuclear Information System (INIS)

    Sato, Toshihiro

    2008-01-01

    Myc gene has been suggested to be one of radiation targets in early genesis of γ ray-induced thymic lymphoma where Myc trisomy often occurs, and Myc activation results in p53 activation and apoptosis. The purpose of this study is to see the effects of radiation and mutation on Myc activation in the mouse. The lymphoma was induced by a single exposure of 3 Gy γ ray in BALB/c Bcl11b/Rit+/- and MSM p53-/- mice at 4 weeks after birth and by 4 weekly exposures of 2.5 Gy in p53+/- mouse. Genetic allele analysis for trisomy identification in the lymphoma was done by quantitative PCR using brain DNA as a control. Myc trisomy was found in the lymphoma of p53+/- mouse in 62% (23/37 animals) and of p53+/+, 66% (23/25), a similar frequency, suggesting that the target of radiation was not only the Myc activation. In addition, Myc trisomy frequency was 15% (4/27) in the lymphoma of Bcl11b+/+p53+/- and 36% (9/25), in heterozygote Bcl11b+/-. This finding suggested that the functional failure of Bcl11b reduced the contribution of Myc trisomy to the genesis. It was concluded that contribution of Myc trisomy to genesis of the lymphoma was dependent on genetic predisposition, and Myc-activated-, Bcl11b/Rit1-signal pathways played a parallel role in the genesis. (R.T.)

  19. Mcm2 deficiency results in short deletions allowing high resolution identification of genes contributing to lymphoblastic lymphoma

    Science.gov (United States)

    Rusiniak, Michael E.; Kunnev, Dimiter; Freeland, Amy; Cady, Gillian K.; Pruitt, Steven C.

    2011-01-01

    Mini-chromosome maintenance (Mcm) proteins are part of the replication licensing complex that is loaded onto chromatin during the G1-phase of the cell cycle and required for initiation of DNA replication in the subsequent S-phase. Mcm proteins are typically loaded in excess of the number of locations that are utilized during S-phase. Nonetheless, partial depletion of Mcm proteins leads to cancers and stem cell deficiencies. Mcm2 deficient mice, on a 129Sv genetic background, display a high rate of thymic lymphoblastic lymphoma. Here array comparative genomic hybridization (aCGH) is utilized to characterize the genetic damage accruing in these tumors. The predominant events are deletions averaging less than 0.5 Mb, considerably shorter than observed in prior studies using alternative mouse lymphoma models or human tumors. Such deletions facilitate identification of specific genes and pathways responsible for the tumors. Mutations in many genes that have been implicated in human lymphomas are recapitulated in this mouse model. These features, and the fact that the mutation underlying the accelerated genetic damage does not target a specific gene or pathway a priori, are valuable features of this mouse model for identification of tumor suppressor genes. Genes affected in all tumors include Pten, Tcfe2a, Mbd3 and Setd1b. Notch1 and additional genes are affected in subsets of tumors. The high frequency of relatively short deletions is consistent with elevated recombination between nearby stalled replication forks in Mcm2 deficient mice. PMID:22158038

  20. Mouse model of Epstein-Barr virus LMP1- and LMP2A-driven germinal center B-cell lymphoproliferative disease.

    Science.gov (United States)

    Minamitani, Takeharu; Ma, Yijie; Zhou, Hufeng; Kida, Hiroshi; Tsai, Chao-Yuan; Obana, Masanori; Okuzaki, Daisuke; Fujio, Yasushi; Kumanogoh, Atsushi; Zhao, Bo; Kikutani, Hitoshi; Kieff, Elliott; Gewurz, Benjamin E; Yasui, Teruhito

    2017-05-02

    Epstein-Barr virus (EBV) is a major cause of immunosuppression-related B-cell lymphomas and Hodgkin lymphoma (HL). In these malignancies, EBV latent membrane protein 1 (LMP1) and LMP2A provide infected B cells with surrogate CD40 and B-cell receptor growth and survival signals. To gain insights into their synergistic in vivo roles in germinal center (GC) B cells, from which most EBV-driven lymphomas arise, we generated a mouse model with conditional GC B-cell LMP1 and LMP2A coexpression. LMP1 and LMP2A had limited effects in immunocompetent mice. However, upon T- and NK-cell depletion, LMP1/2A caused massive plasmablast outgrowth, organ damage, and death. RNA-sequencing analyses identified EBV oncoprotein effects on GC B-cell target genes, including up-regulation of multiple proinflammatory chemokines and master regulators of plasma cell differentiation. LMP1/2A coexpression also up-regulated key HL markers, including CD30 and mixed hematopoietic lineage markers. Collectively, our results highlight synergistic EBV membrane oncoprotein effects on GC B cells and provide a model for studies of their roles in immunosuppression-related lymphoproliferative diseases.

  1. [Regulatory T cells inhibit proliferation of mouse lymphoma cell line EL4 in vitro].

    Science.gov (United States)

    Zhang, Chen; Kong, Yan; Guo, Jun; Ying, Zhi-Tao; Yuan, Zhi-Hong; Zhang, Yun-Tao; Zheng, Wen; Song, Yu-Qin; Li, Ping-Ping; Zhu, Jun

    2010-10-01

    This study was aimed to investigate the effect of regulatory T (Treg) cells on the T cell lymphoma EL4 cells and its mechanism in vitro. C57BL/6 mouse Treg cells were isolated by magnetic cell sorting (MACS). The purity of Treg cells and their expression of Foxp3 were identified by flow cytometry (FCM) and PT-PCR respectively. The suppression of Treg cells on EL4 cells was detected by 3H-TdR method. At the same time, enzyme-linked immunosorbent assay (ELISA) was used to detect the secretion of cytokine TGF-β1 and IL-10. The results showed that CD4+CD25+ T cells could be successfully isolated by MACS with the purity reaching 94.52% and the expression of Foxp3 reaching 84.72%. After sorting, the expression of Foxp3 mRNA could be detected by RT-PCR. 3H-TdR assay confirmed that regulatory T cells could suppress the proliferation of EL4 cells with or without antigen presenting cells (APC) or dendritic cells (DC), APC or DC might effectively enhance the suppression. In addition, DC alone also suppressed the proliferation. TGF-β1 and IL-10 could be detected in the supernatant by ELISA. It is concluded that the Treg cells can obviously suppress the proliferation of T cell lymphoma cells in vitro, APC or DC can enhance this suppressive effect, while the DC alone also can suppress the proliferation of EL4 cells, the TGF-β1 and IL-10 cytokine pathway may be one of the mechanisms of suppression.

  2. Burn mouse models

    DEFF Research Database (Denmark)

    Calum, Henrik; Høiby, Niels; Moser, Claus

    2014-01-01

    Severe thermal injury induces immunosuppression, involving all parts of the immune system, especially when large fractions of the total body surface area are affected. An animal model was established to characterize the burn-induced immunosuppression. In our novel mouse model a 6 % third-degree b......Severe thermal injury induces immunosuppression, involving all parts of the immune system, especially when large fractions of the total body surface area are affected. An animal model was established to characterize the burn-induced immunosuppression. In our novel mouse model a 6 % third...... with infected burn wound compared with the burn wound only group. The burn mouse model resembles the clinical situation and provides an opportunity to examine or develop new strategies like new antibiotics and immune therapy, in handling burn wound victims much....

  3. Identification of Candidate B-Lymphoma Genes by Cross-Species Gene Expression Profiling

    Science.gov (United States)

    Tompkins, Van S.; Han, Seong-Su; Olivier, Alicia; Syrbu, Sergei; Bair, Thomas; Button, Anna; Jacobus, Laura; Wang, Zebin; Lifton, Samuel; Raychaudhuri, Pradip; Morse, Herbert C.; Weiner, George; Link, Brian; Smith, Brian J.; Janz, Siegfried

    2013-01-01

    Comparative genome-wide expression profiling of malignant tumor counterparts across the human-mouse species barrier has a successful track record as a gene discovery tool in liver, breast, lung, prostate and other cancers, but has been largely neglected in studies on neoplasms of mature B-lymphocytes such as diffuse large B cell lymphoma (DLBCL) and Burkitt lymphoma (BL). We used global gene expression profiles of DLBCL-like tumors that arose spontaneously in Myc-transgenic C57BL/6 mice as a phylogenetically conserved filter for analyzing the human DLBCL transcriptome. The human and mouse lymphomas were found to have 60 concordantly deregulated genes in common, including 8 genes that Cox hazard regression analysis associated with overall survival in a published landmark dataset of DLBCL. Genetic network analysis of the 60 genes followed by biological validation studies indicate FOXM1 as a candidate DLBCL and BL gene, supporting a number of studies contending that FOXM1 is a therapeutic target in mature B cell tumors. Our findings demonstrate the value of the “mouse filter” for genomic studies of human B-lineage neoplasms for which a vast knowledge base already exists. PMID:24130802

  4. The 5T mouse multiple myeloma model: Absence of c-myc oncogene rearrangement in early transplant generations

    NARCIS (Netherlands)

    Radl, J.; Punt, Y.A.; Enden-Vieveen, M.H.M. van den; Bentvelzen, P.A.J.; Bakkus, M.H.C.; Akker T., W. van den; Benner, R.

    1990-01-01

    Consistent chromosomal translocations involving the c-myc cellular oncogene and one of the three immunoglobulin loci are typical for human Burkitt's lymphoma, induced mouse plasmacytoma (MPC) and spontaneously arising rat immunocytoma (RIC). Another plasma cell malignancy, multiple myeloma (MM),

  5. ONC201 induces cell death in pediatric non-Hodgkin's lymphoma cells.

    Science.gov (United States)

    Talekar, Mala K; Allen, Joshua E; Dicker, David T; El-Deiry, Wafik S

    2015-08-03

    ONC201/TIC10 is a small molecule initially discovered by its ability to coordinately induce and activate the TRAIL pathway selectively in tumor cells and has recently entered clinical trials in adult advanced cancers. The anti-tumor activity of ONC201 has previously been demonstrated in several preclinical models of cancer, including refractory solid tumors and a transgenic lymphoma mouse model. Based on the need for new safe and effective therapies in pediatric non-Hodgkin's lymphoma (NHL) and the non-toxic preclinical profile of ONC201, we investigated the in vitro efficacy of ONC201 in non-Hodgkin's lymphoma (NHL) cell lines to evaluate its therapeutic potential for this disease. ONC201 caused a dose-dependent reduction in the cell viability of NHL cell lines that resulted from induction of apoptosis. As expected from prior observations, induction of TRAIL and its receptor DR5 was also observed in these cell lines. Furthermore, dual induction of TRAIL and DR5 appeared to drive the observed apoptosis and TRAIL expression was correlated linearly with sub-G1 DNA content, suggesting its potential role as a biomarker of tumor response to ONC201-treated lymphoma cells. We further investigated combinations of ONC201 with approved chemotherapeutic agents used to treat lymphoma. ONC201 exhibited synergy in combination with the anti-metabolic agent cytarabine in vitro, in addition to cooperating with other therapies. Together these findings indicate that ONC201 is an effective TRAIL pathway-inducer as a monoagent that can be combined with chemotherapy to enhance therapeutic responses in pediatric NHL.

  6. Rituximab in the treatment of primary cutaneous B-cell lymphoma: a review.

    Science.gov (United States)

    Fernández-Guarino, M; Ortiz-Romero, P L; Fernández-Misa, R; Montalbán, C

    2014-06-01

    Rituximab is a chimeric mouse-human antibody that targets the CD20 antigen, which is found in both normal and neoplastic B cells. In recent years, it has been increasingly used to treat cutaneous B-cell lymphoma and is now considered an alternative to classic treatment (radiotherapy and surgery) of 2 types of indolent lymphoma, namely, primary cutaneous follicle center lymphoma and primary cutaneous marginal zone B-cell lymphoma. Rituximab is also administered as an alternative to polychemotherapy in the treatment of primary cutaneous large B-cell lymphoma, leg type. Its use as an alternative drug led to it being administered intralesionally, with beneficial effects. In the present article, we review the literature published on the use of rituximab to treat primary cutaneous B-cell lymphoma. Copyright © 2012 Elsevier España, S.L. and AEDV. All rights reserved.

  7. Farnesyl transferase inhibitors induce extended remissions in transgenic mice with mature B cell lymphomas

    Directory of Open Access Journals (Sweden)

    Refaeli Yosef

    2008-05-01

    Full Text Available Abstract Background We have used a mouse model based on overexpression of c-Myc in B cells genetically engineered to be self-reactive to test the hypothesis that farnesyl transferase inhibitors (FTIs can effectively treat mature B cell lymphomas. FTIs are undergoing clinical trials to treat both lymphoid and non-lymphoid malignancies and we wished to obtain evidence to support the inclusion of B cell lymphomas in future trials. Results We report that two FTIs, L-744,832 and SCH66336, blocked the growth of mature B cell lymphoma cells in vitro and in vivo. The FTI treatment affected the proliferation and survival of the transformed B cells to a greater extent than naïve B cells stimulated with antigen. In syngeneic mice transplanted with the transgenic lymphoma cells, L-744,832 treatment prevented the growth of the tumor cells and the morbidity associated with the resulting lymphoma progression. Tumors that arose from transplantation of the lymphoma cells regressed with as little as three days of treatment with L-744,832 or SCH66336. Treatment of these established lymphomas with L-744,832 for seven days led to long-term remission of the disease in approximately 25% of animals. Conclusion FTI treatment can block the proliferation and survival of self-reactive transformed B cells that overexpress Myc. In mice transplanted with mature B cell lymphomas, we found that FTI treatment led to regression of disease. FTIs warrant further consideration as therapeutic agents for mature B cell lymphomas and other lymphoid tumors.

  8. Color-Coded Imaging of Syngeneic Orthotopic Malignant Lymphoma Interacting with Host Stromal Cells During Metastasis.

    Science.gov (United States)

    Matsumoto, Takuro; Suetsugu, Atsushi; Hasegawa, Kosuke; Nakamura, Miki; Aoki, Hitomi; Kunisada, Takahiro; Tsurumi, Hisashi; Shimizu, Masahito; Hoffman, Robert M

    2016-04-01

    The EL4 cell line was previously derived from a lymphoma induced in a C57/BL6 mouse by 9,10-dimethyl-1,2-benzanthracene. In a previous study, EL4 lymphoma cells expressing red fluorescent protein (EL4-RFP) were established and injected into the tail vein of C57/BL6 green fluorescent protein (GFP) transgenic mice. Metastasis was observed at multiple sites which were also enriched with host GFP-expressing stromal cells. In the present study, our aim was to establish an orthotopic model of EL4-RFP. In the present study, EL4-RFP lymphoma cells were injected in the spleen of C57/BL6 GFP transgenic mice as an orthotopic model of lymphoma. Resultant primary tumor and metastases were imaged with the Olympus FV1000 scanning laser confocal microscope. EL4-RFP metastasis was observed 21 days later. EL4-RFP tumors in the spleen (primary injection site), liver, supra-mediastinum lymph nodes, abdominal lymph nodes, bone marrow, and lung were visualized by color-coded imaging. EL4-RFP metastases in the liver, lymph nodes, and bone marrow in C57/BL6 GFP mice were rich in GFP stromal cells such as macrophages, fibroblasts, dendritic cells, and normal lymphocytes derived from the host animal. Small tumors were observed in the spleen, which were rich in host stromal cells. In the lung, no mass formation of lymphoma cells occurred, but lymphoma cells circulated in lung peripheral blood vessels. Phagocytosis of EL4-RFP lymphoma cells by macrophages, as well as dendritic cells and fibroblasts, were observed in culture. Color-coded imaging of the lymphoma microenvironment suggests an important role of stromal cells in lymphoma progression and metastasis. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  9. Allele-specific deletions in mouse tumors identify Fbxw7 as germline modifier of tumor susceptibility.

    Directory of Open Access Journals (Sweden)

    Jesus Perez-Losada

    Full Text Available Genome-wide association studies (GWAS have been successful in finding associations between specific genetic variants and cancer susceptibility in human populations. These studies have identified a range of highly statistically significant associations between single nucleotide polymorphisms (SNPs and susceptibility to development of a range of human tumors. However, the effect of each SNP in isolation is very small, and all of the SNPs combined only account for a relatively minor proportion of the total genetic risk (5-10%. There is therefore a major requirement for alternative routes to the discovery of genetic risk factors for cancer. We have previously shown using mouse models that chromosomal regions harboring susceptibility genes identified by linkage analysis frequently exhibit allele-specific genetic alterations in tumors. We demonstrate here that the Fbxw7 gene, a commonly mutated gene in a wide range of mouse and human cancers, shows allele-specific deletions in mouse lymphomas and skin tumors. Lymphomas from three different F1 hybrids show 100% allele-specificity in the patterns of allelic loss. Parental alleles from 129/Sv or Spretus/Gla mice are lost in tumors from F1 hybrids with C57BL/6 animals, due to the presence of a specific non-synonymous coding sequence polymorphism at the N-terminal portion of the gene. A specific genetic test of association between this SNP and lymphoma susceptibility in interspecific backcross mice showed a significant linkage (p = 0.001, but only in animals with a functional p53 gene. These data therefore identify Fbxw7 as a p53-dependent tumor susceptibility gene. Increased p53-dependent tumor susceptibility and allele-specific losses were also seen in a mouse skin model of skin tumor development. We propose that analysis of preferential allelic imbalances in tumors may provide an efficient means of uncovering genetic variants that affect mouse and human tumor susceptibility.

  10. Development and validation of multivariable predictive model for thromboembolic events in lymphoma patients.

    Science.gov (United States)

    Antic, Darko; Milic, Natasa; Nikolovski, Srdjan; Todorovic, Milena; Bila, Jelena; Djurdjevic, Predrag; Andjelic, Bosko; Djurasinovic, Vladislava; Sretenovic, Aleksandra; Vukovic, Vojin; Jelicic, Jelena; Hayman, Suzanne; Mihaljevic, Biljana

    2016-10-01

    Lymphoma patients are at increased risk of thromboembolic events but thromboprophylaxis in these patients is largely underused. We sought to develop and validate a simple model, based on individual clinical and laboratory patient characteristics that would designate lymphoma patients at risk for thromboembolic event. The study population included 1,820 lymphoma patients who were treated in the Lymphoma Departments at the Clinics of Hematology, Clinical Center of Serbia and Clinical Center Kragujevac. The model was developed using data from a derivation cohort (n = 1,236), and further assessed in the validation cohort (n = 584). Sixty-five patients (5.3%) in the derivation cohort and 34 (5.8%) patients in the validation cohort developed thromboembolic events. The variables independently associated with risk for thromboembolism were: previous venous and/or arterial events, mediastinal involvement, BMI>30 kg/m(2) , reduced mobility, extranodal localization, development of neutropenia and hemoglobin level 3). For patients classified at risk (intermediate and high-risk scores), the model produced negative predictive value of 98.5%, positive predictive value of 25.1%, sensitivity of 75.4%, and specificity of 87.5%. A high-risk score had positive predictive value of 65.2%. The diagnostic performance measures retained similar values in the validation cohort. Developed prognostic Thrombosis Lymphoma - ThroLy score is more specific for lymphoma patients than any other available score targeting thrombosis in cancer patients. Am. J. Hematol. 91:1014-1019, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  11. Locus specificity in the mutability of mouse lymphoma strain LY-S

    International Nuclear Information System (INIS)

    Evans, H.H.; Mencl, J.; Horng, M.F.

    1985-01-01

    Mouse lymphoma L5178Y strains, LY-R and LY-S, are closely related but differ in their sensitivity to the lethal effects of radiation and various chemicals. Strain LY-S was originally isolated in 1961 following a spontaneous change in the sensitivity of cultured LY-R cells to ionizing radiation. The authors previously reported that, although strain LY-S is more sensitive to the lethal effects of ionizing radiation and alkylating agents than strain LY-R, it is markedly less mutable than strain LY-R at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus. The isolated sublines of strains LY-R and LY-S which are heterozygous at the thymidine kinase (TK) locus. The LY-S TK+/- heterozygote, like its TK+/+ parent, is more sensitive to the lethal effects of ionizing radiation and alkylating agents and less mutable at the HGPRT locus by these agents than the LY-R TK+/- heterozygote. However, the LY-S heterozygote is 100 times more mutable by these agents at the TK locus than at the HGRT locus. In contrast to LY-R, the majority of the spontaneous and induced LY-S TK-/- mutants form small colonies in the presence of trifluorothymidine, indicating that in the LY-S heterozygote, the inactivation of the TK gene is accompanied by damage to, or rearrangement of neighboring genes

  12. Lymphoma Caused by Intestinal Microbiota

    Directory of Open Access Journals (Sweden)

    Mitsuko L. Yamamoto

    2014-09-01

    Full Text Available The intestinal microbiota and gut immune system must constantly communicate to maintain a balance between tolerance and activation: on the one hand, our immune system should protect us from pathogenic microbes and on the other hand, most of the millions of microbes in and on our body are innocuous symbionts and some can even be beneficial. Since there is such a close interaction between the immune system and the intestinal microbiota, it is not surprising that some lymphomas such as mucosal-associated lymphoid tissue (MALT lymphoma have been shown to be caused by the presence of certain bacteria. Animal models played an important role in establishing causation and mechanism of bacteria-induced MALT lymphoma. In this review we discuss different ways that animal models have been applied to establish a link between the gut microbiota and lymphoma and how animal models have helped to elucidate mechanisms of microbiota-induced lymphoma. While there are not a plethora of studies demonstrating a connection between microbiota and lymphoma development, we believe that animal models are a system which can be exploited in the future to enhance our understanding of causation and improve prognosis and treatment of lymphoma.

  13. Radioimmunotherapy of Non-Hodgkin's Lymphoma. The interaction of radiation and antibody with lymphoma cells

    International Nuclear Information System (INIS)

    Illidge, T.M.

    1999-06-01

    Whilst many patients with indolent Non-Hodgkin's Lymphoma (NHL) can achieve clinical remissions to first-line chemotherapy and/or radiotherapy, most will relapse. Current treatment options for relapsing patients are limited since most patients become resistant to repeated chemotherapy. Death usually occurs within 10 years of diagnosis. Overall, these disappointing results have not changed significantly in a quarter of a century and clearly advocate the urgent priority to research into potential new therapeutic approaches into this diverse and increasingly prevalent group of human tumours. Radioimmunotherapy (RIT) is currently under investigation as a new approach for the treatment of this disease. In this form of treatment, radionuclide-labeled monoclonal antibodies are able to deliver selective systemic irradiation by recognising tumour-associated antigens. The use of RIT with radiolabeled anti-CD20 antibodies in patients with recurrent B-cell lymphoma has resulted in extremely high rates of durable complete remissions. The optimal approach and mechanisms of action of successful RIT remain however largely unknown. The work described in this thesis has focused on clarifying some of the important determinants and mechanisms of effective RIT of syngeneic B-cell lymphoma, both in vivo and in vitro. A successful animal model of RIT in B cell lymphomas was established by initially generating a panel of antibodies against mouse B cell antigens. The in vitro characteristics of these antibodies have been compared with their subsequent performance, in biodistribution studies and RIT in vivo. For the first time in an in vivo model the relative contributions of antibody and irradiation are described. Some antibodies including anti-MHC Class II were shown to be effective delivery vehicles of low doses of Iodine-131. These antibodies, which appear to be inactive delivery vehicles can cure animals with low burdens of tumour. However antibodies such as anti-idiotype and anti-CD40

  14. Effect of Bcl11b genotypes and γ-radiation on the development of mouse thymic lymphomas

    International Nuclear Information System (INIS)

    Yoshikai, Yoshihiro; Sato, Toshihiro; Morita, Shinichi; Kohara, Yuki; Takagi, Ritsuo; Mishima, Yukio; Kominami, Ryo

    2008-01-01

    Bcl11b is a haploinsufficient tumor suppressor gene and expressed in many tissues such as thymus, brain and skin. Irradiated Bcl11b +/- heterozygous mice mostly develop thymic lymphomas, but the preference of Bcl11b inactivation for thymic lymphomas remains to be addressed. We produced Bcl11b +/- heterozygous and Bcl11b wild-type mice of p53 +/- background and compared their incidence of γ-ray induced thymic lymphomas. Majority of the tumors in p53 +/- mice were skin tumors, and only 5 (36%) of the 14 tumors were thymic lymphomas. In contrast, Bcl11b +/- p53 +/- doubly heterozygous mice developed thymic lymphomas at the frequency of 27 (79%) of the 34 tumors developed (P = 0.008). This indicates the preference of Bcl11b impairment for thymic lymphoma development. We also analyzed loss of the wild-type alleles in the 27 lymphomas, a predicted consequence given by γ-irradiation. However, the loss frequency was low, only six (22%) for Bcl11b and five (19%) for p53. The frequencies did not differ from those of spontaneously developed thymic lymphomas in the doubly heterozygous mice, though the latency of lymphoma development markedly differed between them. This suggests that the main contribution of irradiation at least in those mice is not for the tumor initiation by inducing allelic losses but probably for the promotion of thymic lymphoma development

  15. The Role of Cyclin D1 in the Chemoresistance of Mantle Cell Lymphoma

    Science.gov (United States)

    2016-09-01

    additional to t(11;14) and generation of a mouse model . Cancer Genet Cytogenet. 2003;143:32–38. [23] Amin HM, McDonnell TJ, Medeiros LJ, et al...12 h after drug removal. However, in CCND1 KD cells, there was 2.5-fold increase in mitosis , as detected by phosphorylation of Ser10 in histone H3...Francis Group LEUKEMIA & LYMPHOMA, 2016 http://dx.doi.org/10.1080/10428194.2016.1198958 and primary MCL cells in vitro and in a xenotransplant model

  16. Retroviral insertions in the VISION database identify molecular pathways in mouse lymphoid leukemia and lymphoma.

    Science.gov (United States)

    Weiser, Keith C; Liu, Bin; Hansen, Gwenn M; Skapura, Darlene; Hentges, Kathryn E; Yarlagadda, Sujatha; Morse Iii, Herbert C; Justice, Monica J

    2007-10-01

    AKXD recombinant inbred (RI) strains develop a variety of leukemias and lymphomas due to somatically acquired insertions of retroviral DNA into the genome of hematopoetic cells that can mutate cellular proto-oncogenes and tumor suppressor genes. We generated a new set of tumors from nine AKXD RI strains selected for their propensity to develop B-cell tumors, the most common type of human hematopoietic cancers. We employed a PCR technique called viral insertion site amplification (VISA) to rapidly isolate genomic sequence at the site of provirus insertion. Here we describe 550 VISA sequence tags (VSTs) that identify 74 common insertion sites (CISs), of which 21 have not been identified previously. Several suspected proto-oncogenes and tumor suppressor genes lie near CISs, providing supportive evidence for their roles in cancer. Furthermore, numerous previously uncharacterized genes lie near CISs, providing a pool of candidate disease genes for future research. Pathway analysis of candidate genes identified several signaling pathways as common and powerful routes to blood cancer, including Notch, E-protein, NFkappaB, and Ras signaling. Misregulation of several Notch signaling genes was confirmed by quantitative RT-PCR. Our data suggest that analyses of insertional mutagenesis on a single genetic background are biased toward the identification of cooperating mutations. This tumor collection represents the most comprehensive study of the genetics of B-cell leukemia and lymphoma development in mice. We have deposited the VST sequences, CISs in a genome viewer, histopathology, and molecular tumor typing data in a public web database called VISION (Viral Insertion Sites Identifying Oncogenes), which is located at http://www.mouse-genome.bcm.tmc.edu/vision .

  17. Reduction of Myeloid-derived Suppressor Cells and Lymphoma Growth by a Natural Triterpenoid

    Science.gov (United States)

    Radwan, Faisal F. Y.; Hossain, Azim; God, Jason M.; Leaphart, Nathan; Elvington, Michelle; Nagarkatti, Mitzi; Tomlinson, Stephen; Haque, Azizul

    2016-01-01

    Lymphoma is a potentially life threatening disease. The goal of this study was to investigate the therapeutic potential of a natural triterpenoid, Ganoderic acid A (GA-A) in controlling lymphoma growth both in vitro and in vivo. Here, we show that GA-A treatment induces caspase-dependent apoptotic cell death characterized by a dose-dependent increase in active caspases 9 and 3, up-regulation of pro-apoptotic BIM and BAX proteins, and a subsequent loss of mitochondrial membrane potential with release of cytochrome c. In addition to GA-A’s anti-growth activity, we show that lower doses of GA-A enhance HLA class II-mediated antigen presentation and CD4+ T cell recognition of lymphoma in vitro. The therapeutic relevance of GA-A treatment was also tested in vivo using the EL4 syngeneic mouse model of metastatic lymphoma. GA-A-treatment significantly prolonged survival of EL4 challenged mice and decreased tumor metastasis to the liver, an outcome accompanied by a marked down-regulation of STAT3 phosphorylation, reduction myeloid-derived suppressor cells (MDSCs), and enhancement of cytotoxic CD8+ T cells in the host. Thus, GA-A not only selectively induces apoptosis in lymphoma cells, but also enhances cell-mediated immune responses by attenuating MDSCs, and elevating Ag presentation and T cell recognition. The demonstrated therapeutic benefit indicates that GA-A is a candidate for future drug design for the treatment of lymphoma. PMID:25142864

  18. Reduction of myeloid-derived suppressor cells and lymphoma growth by a natural triterpenoid.

    Science.gov (United States)

    Radwan, Faisal F Y; Hossain, Azim; God, Jason M; Leaphart, Nathan; Elvington, Michelle; Nagarkatti, Mitzi; Tomlinson, Stephen; Haque, Azizul

    2015-01-01

    Lymphoma is a potentially life threatening disease. The goal of this study was to investigate the therapeutic potential of a natural triterpenoid, Ganoderic acid A (GA-A) in controlling lymphoma growth both in vitro and in vivo. Here, we show that GA-A treatment induces caspase-dependent apoptotic cell death characterized by a dose-dependent increase in active caspases 9 and 3, up-regulation of pro-apoptotic BIM and BAX proteins, and a subsequent loss of mitochondrial membrane potential with release of cytochrome c. In addition to GA-A's anti-growth activity, we show that lower doses of GA-A enhance HLA class II-mediated antigen (Ag) presentation and CD4+ T cell recognition of lymphoma cells in vitro. The therapeutic relevance of GA-A treatment was also tested in vivo using the EL4 syngeneic mouse model of metastatic lymphoma. GA-A-treatment significantly prolonged survival of EL4 challenged mice and decreased tumor metastasis to the liver, an outcome accompanied by a marked down-regulation of STAT3 phosphorylation, reduction myeloid-derived suppressor cells (MDSCs), and enhancement of cytotoxic CD8+ T cells in the host. Thus, GA-A not only selectively induces apoptosis in lymphoma cells, but also enhances cell-mediated immune responses by attenuating MDSCs, and elevating Ag presentation and T cell recognition. The demonstrated therapeutic benefit indicates that GA-A is a candidate for future drug design for the treatment of lymphoma. © 2014 Wiley Periodicals, Inc.

  19. Human bone marrow mesenchymal stem cells display anti-cancer activity in SCID mice bearing disseminated non-Hodgkin's lymphoma xenografts.

    Directory of Open Access Journals (Sweden)

    Paola Secchiero

    Full Text Available BACKGROUND: Although multimodality treatment can induce high rate of remission in many subtypes of non-Hodgkin's lymphoma (NHL, significant proportions of patients relapse with incurable disease. The effect of human bone marrow (BM mesenchymal stem cells (MSC on tumor cell growth is controversial, and no specific information is available on the effect of BM-MSC on NHL. METHODOLOGY/PRINCIPAL FINDINGS: The effect of BM-MSC was analyzed in two in vivo models of disseminated non-Hodgkin's lymphomas with an indolent (EBV(- Burkitt-type BJAB, median survival = 46 days and an aggressive (EBV(+ B lymphoblastoid SKW6.4, median survival = 27 days behavior in nude-SCID mice. Intra-peritoneal (i.p. injection of MSC (4 days after i.p. injection of lymphoma cells significantly increased the overall survival at an optimal MSC:lymphoma ratio of 1:10 in both xenograft models (BJAB+MSC, median survival = 58.5 days; SKW6.4+MSC, median survival = 40 days. Upon MSC injection, i.p. tumor masses developed more slowly and, at the histopathological observation, exhibited a massive stromal infiltration coupled to extensive intra-tumor necrosis. In in vitro experiments, we found that: i MSC/lymphoma co-cultures modestly affected lymphoma cell survival and were characterized by increased release of pro-angiogenic cytokines with respect to the MSC, or lymphoma, cultures; ii MSC induce the migration of endothelial cells in transwell assays, but promoted endothelial cell apoptosis in direct MSC/endothelial cell co-cultures. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate that BM-MSC exhibit anti-lymphoma activity in two distinct xenograft SCID mouse models of disseminated NHL.

  20. Reduced TET2 function leads to T-cell lymphoma with follicular helper T-cell-like features in mice

    International Nuclear Information System (INIS)

    Muto, H; Sakata-Yanagimoto, M; Nagae, G; Shiozawa, Y; Miyake, Y; Yoshida, K; Enami, T; Kamada, Y; Kato, T; Uchida, K; Nanmoku, T; Obara, N; Suzukawa, K; Sanada, M; Nakamura, N; Aburatani, H; Ogawa, S; Chiba, S

    2014-01-01

    TET2 (Ten Eleven Translocation 2) is a dioxygenase that converts methylcytosine (mC) to hydroxymethylcytosine (hmC). TET2 loss-of-function mutations are highly frequent in subtypes of T-cell lymphoma that harbor follicular helper T (Tfh)-cell-like features, such as angioimmunoblastic T-cell lymphoma (30–83%) or peripheral T-cell lymphoma, not otherwise specified (10–49%), as well as myeloid malignancies. Here, we show that middle-aged Tet2 knockdown (Tet2 gt/gt ) mice exhibit Tfh-like cell overproduction in the spleen compared with control mice. The Tet2 knockdown mice eventually develop T-cell lymphoma with Tfh-like features after a long latency (median 67 weeks). Transcriptome analysis revealed that these lymphoma cells had Tfh-like gene expression patterns when compared with splenic CD4-positive cells of wild-type mice. The lymphoma cells showed lower hmC densities around the transcription start site (TSS) and higher mC densities at the regions of the TSS, gene body and CpG islands. These epigenetic changes, seen in Tet2 insufficiency-triggered lymphoma, possibly contributed to predated outgrowth of Tfh-like cells and subsequent lymphomagenesis. The mouse model described here suggests that TET2 mutations play a major role in the development of T-cell lymphoma with Tfh-like features in humans

  1. [Antitumor effects of matrix protein of vesicular stomatic virus on EL4 lymphoma mice].

    Science.gov (United States)

    Lin, Shi-jia; Yu, Qin-mei; Meng, Wen-tong; Wen, Yan-jun; Chen, Li-juan; Niu, Ting

    2011-03-01

    To explore antitumor effects of plasmid pcDNA3. 1-MP encoding matrix protein of vesicular stomatitis virus (VSV) complexed with cationic liposome (DOTAP:CHOL) in mice with EL4 lymphoma. C57BL/6 mouse model with EL4 lymphoma was established. Sixty mice bearing EL4 lymphoma were divided randomly into five groups including Lip-MP, Lip-pVAX, Lip, ADM and NS groups, which were intravenously injected with liposome-pcDNA 3. 1-MP complex, liposome-pVAX complex, empty liposome, Adriamycin and normal saline respectively every three days. Tumor volumes and survival time were monitored. Microvessel density and tumor proliferative index in tumor tissues were determined by CD31, Ki-67 immunohistochemistry staining, meanwhile the tumor apoptosis index was measured by TUNEL method. From 6 days after treatments on, the tumor volume in Lip-MP group was much smaller than that in Lip-pVAX, Lip and NS group (P EL4 tumor cells in vivo (P EL4 lymphoma, which may be related to the induction of tumor cell apoptosis, inhibition of tumor angiogenesis, and suppression of tumor cell proliferation.

  2. Radioimmunotherapy of Non-Hodgkin's Lymphoma. The interaction of radiation and antibody with lymphoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Illidge, T.M

    1999-06-01

    Whilst many patients with indolent Non-Hodgkin's Lymphoma (NHL) can achieve clinical remissions to first-line chemotherapy and/or radiotherapy, most will relapse. Current treatment options for relapsing patients are limited since most patients become resistant to repeated chemotherapy. Death usually occurs within 10 years of diagnosis. Overall, these disappointing results have not changed significantly in a quarter of a century and clearly advocate the urgent priority to research into potential new therapeutic approaches into this diverse and increasingly prevalent group of human tumours. Radioimmunotherapy (RIT) is currently under investigation as a new approach for the treatment of this disease. In this form of treatment, radionuclide-labeled monoclonal antibodies are able to deliver selective systemic irradiation by recognising tumour-associated antigens. The use of RIT with radiolabeled anti-CD20 antibodies in patients with recurrent B-cell lymphoma has resulted in extremely high rates of durable complete remissions. The optimal approach and mechanisms of action of successful RIT remain however largely unknown. The work described in this thesis has focused on clarifying some of the important determinants and mechanisms of effective RIT of syngeneic B-cell lymphoma, both in vivo and in vitro. A successful animal model of RIT in B cell lymphomas was established by initially generating a panel of antibodies against mouse B cell antigens. The in vitro characteristics of these antibodies have been compared with their subsequent performance, in biodistribution studies and RIT in vivo. For the first time in an in vivo model the relative contributions of antibody and irradiation are described. Some antibodies including anti-MHC Class II were shown to be effective delivery vehicles of low doses of Iodine-131. These antibodies, which appear to be inactive delivery vehicles can cure animals with low burdens of tumour. However antibodies such as anti-idiotype and anti

  3. Co-targeting of Tiam1/Rac1 and Notch ameliorates chemoresistance against doxorubicin in a biomimetic 3D lymphoma model

    Science.gov (United States)

    Ikram, Muhammad; Lim, Yeseon; Baek, Sun-Yong; Jin, Songwan; Jeong, Young Hun; Kwak, Jong-Young; Yoon, Sik

    2018-01-01

    Lymphoma is a heterogeneous disease with a highly variable clinical course and prognosis. Improving the prognosis for patients with relapsed and treatment-resistant lymphoma remains challenging. Current in vitro drug testing models based on 2D cell culture lack natural tissue-like structural organization and result in disappointing clinical outcomes. The development of efficient drug testing models using 3D cell culture that more accurately reflects in vivo behaviors is vital. Our aim was to establish an in vitro 3D lymphoma model that can imitate the in vivo 3D lymphoma microenvironment. Using this model, we explored strategies to enhance chemosensitivity to doxorubicin, an important chemotherapeutic drug widely used for the treatment of hematological malignancies. Lymphoma cells grown in this model exhibited excellent biomimetic properties compared to conventional 2D culture including (1) enhanced chemotherapy resistance, (2) suppressed rate of apoptosis, (3) upregulated expression of drug resistance genes (MDR1, MRP1, BCRP and HIF-1α), (4) elevated levels of tumor aggressiveness factors including Notch (Notch-1, -2, -3, and -4) and its downstream molecules (Hes-1 and Hey-1), VEGF and MMPs (MMP-2 and MMP-9), and (5) enrichment of a lymphoma stem cell population. Tiam1, a potential biomarker of tumor progression, metastasis, and chemoresistance, was activated in our 3D lymphoma model. Remarkably, we identified two synergistic therapeutic oncotargets, Tiam1 and Notch, as a strategy to combat resistance against doxorubicin in EL4 T and A20 B lymphoma. Therefore, our data suggest that our 3D lymphoma model is a promising in vitro research platform for studying lymphoma biology and therapeutic approaches. PMID:29416753

  4. Radiation-induced apoptosis in sensitive and resistant cells isolated from a mouse lymphoma

    International Nuclear Information System (INIS)

    Story, M.D.; Voehringer, D.W.; Malone, C.G.; Hobbs, M.L.; Meyn, R.E.

    1994-01-01

    Cells were isolated from a mouse lymphoma (LY-TH) and grown in vitro. They were susceptible to radiation-induced apoptosis after low doses with the appearance of endonucleolytically fragmented DNA 1 h after irradiation. Four hours after receiving 5 Gy, 80% of the DNA was endonucleolytically cleaved. Apoptosis induction by DNA double-strand break (dsb) formation was more effective compared with induction by single-strand break (ssb) formation. After long-term culturing, LY-TH cultures became refractory to apoptosis. Apoptosis-permissive cells (LY-as, cloned from LY-TH cells) were three times more radiosensitive than clonally expanded apoptosis-refractory cells (LY-ar). Low dose-rate irradiation and maintenance at 25 o C for 5 h postirradiation was sparing in LY-ar but not LY-as cells, suggesting a repair deficiency in LY-as cells. Analysis of dsb rejoining kinetics revealed no difference in the initial phase of dsb rejoining. After 1 h, however, relative dsbs in the LY-as variant increased as endonucleolytic cleavage was initiated. Signalling for radiation-induced apoptosis in LY-as cells was independent of the DNA dsb repair pathway and appeared determined by initial events, whereas in LY-ar cells, because of an inhibition in the apoptotic pathway, survival was enhanced and modifiable by repair processes. (author)

  5. Poly (ADP-ribose) metabolism in alkylated mouse L5178Y cells

    International Nuclear Information System (INIS)

    Boyle, J.M.

    1985-01-01

    Poly ADP-ribosylation of two mouse lymphoma cell lines, L5178Y (LS) and the radiation and alkylating agent resistant derivative AII, was investigated by uptake of [ 3 H]NAD by permeabilised cells into acid-precipitable material that was sensitive to phosphodiesterase but insensitive to DNase and RNase. Basal activities in both lymphoma lines were 3-4-fold greater than in mouse L1210 leukaemia cells. However, total endogenous poly (ADP-R) polymerase activity in both L5178Y cell lines, stimulated by a large excess of DNase in the presence of Triton X-100, was less than half the activity in L1210 cells. Doses of N-methyl-N-nitrosourea (MNU) that produced 20-50% survival of colony-forming units increased poly (ADP-R) in both lymphoma lines by only 25% compared with 377% in L1210 cells when synthesis was measured immediately after a 30-min exposure of MNU. Concentrations of 3-aminobenzamide (3AB) above 2.5 mM inhibited colony-forming ability of lymphoma cells and equally inhibited uptake of [ 14 C]formate into protein, RNA and DNA indicating that 3AB behaves as a general metabolic poison. Non-toxic concentrations of 3AB potentiated cell killing by MNU to a similar degree in both lymphoma cell lines. In conclusion, the authors have found little evidence to support the hypothesis that the differential sensitivity of LS and AII is related to poly ADP-ribosylation. Compared with other mouse cells, L5178Y cells appear deficient in poly (ADP-R) polymerase and poly (ADP-R) glycohydrolase activities

  6. CD19 CAR T Cells Expressing IL-12 Eradicate Lymphoma in Fully Lymphoreplete Mice through Induction of Host Immunity

    Directory of Open Access Journals (Sweden)

    Gray Kueberuwa

    2018-03-01

    Full Text Available Chimeric antigen receptor (CAR T cell therapy represents a significant advancement in cancer therapy. Larger studies have shown ∼90% complete remission rates against chemoresistant and/or refractory CD19+ leukemia or lymphoma. Effective CAR T cell therapy is highly dependent on lymphodepleting preconditioning, which is achieved through chemotherapy or radiotherapy that carries with it significant toxicities. These can exclude patients of low performance status. In order to overcome the need for preconditioning, we constructed fully mouse first and second generation anti-murine CD19 CARs with or without interleukin-12 (IL-12 secretion. To test these CARs, we established a mouse model to reflect the human situation without preconditioning. Murine second generation CAR T cells expressing IL-12 were capable of eradicating established B cell lymphoma with a long-term survival rate of ∼25%. We believe this to be the first study in a truly lymphoreplete model. We provide evidence that IL-12-expressing CAR T cells not only directly kill target CD19+ cells, but also recruit host immune cells to an anti-cancer immune response. This finding is critical because lymphodepletion regimens required for the success of current CAR T cell technology eliminate host immune cells whose anti-cancer activity could otherwise be harnessed by strategies such as IL-12-secreting CAR T cells. Keywords: CD19 CAR T cells, IL-12, immunotherapy, chimeric antigen receptor, adoptive cellular therapy, lymphoma, B cell malignancies, TRUCKs, pre-conditioning

  7. Preclinical Evaluation of the Novel BTK Inhibitor Acalabrutinib in Canine Models of B-Cell Non-Hodgkin Lymphoma.

    Directory of Open Access Journals (Sweden)

    Bonnie K Harrington

    Full Text Available Acalabrutinib (ACP-196 is a second-generation inhibitor of Bruton agammaglobulinemia tyrosine kinase (BTK with increased target selectivity and potency compared to ibrutinib. In this study, we evaluated acalabrutinib in spontaneously occurring canine lymphoma, a model of B-cell malignancy similar to human diffuse large B-cell lymphoma (DLBCL. First, we demonstrated that acalabrutinib potently inhibited BTK activity and downstream effectors in CLBL1, a canine B-cell lymphoma cell line, and primary canine lymphoma cells. Acalabrutinib also inhibited proliferation in CLBL1 cells. Twenty dogs were enrolled in the clinical trial and treated with acalabrutinib at dosages of 2.5 to 20mg/kg every 12 or 24 hours. Acalabrutinib was generally well tolerated, with adverse events consisting primarily of grade 1 or 2 anorexia, weight loss, vomiting, diarrhea and lethargy. Overall response rate (ORR was 25% (5/20 with a median progression free survival (PFS of 22.5 days. Clinical benefit was observed in 30% (6/20 of dogs. These findings suggest that acalabrutinib is safe and exhibits activity in canine B-cell lymphoma patients and support the use of canine lymphoma as a relevant model for human non-Hodgkin lymphoma (NHL.

  8. [Study of the immunological mechanism of anti-tumor effects of 5-FU by establishing EL4 tumor-bearing mouse models].

    Science.gov (United States)

    Li, Mo-Lin; Li, Chuan-Gang; Shu, Xiao-Hong; Li, Ming-Xia; Jia, Yu-Jie; Qin, Zhi-Hai

    2007-11-01

    To investigate the immunological mechanism of anti-tumor effect of 5-FU by establishing lymphoma EL4 tumor-bearing mouse models in wild type C57BL/6 mice and nude C57BL/6 mice, respectively. The mouse lymphoma EL4 cells were inoculated subcutaneously into wild type C57BL/6 mice (immune-competent mice). Twelve days later, 5-FU of different doses was administered intraperitoneally to treat these wild type C57BL/6 tumor-bearing mice. The size of tumors in the wild type C57BL/6 mice was observed and recorded to explore the minimal dose of 5-FU that could cure the tumor-bearing mice. Then the same amount of EL4 tumor cells was inoculated subcutaneously into wild type C57BL/6 mice and nude C57BL/6 mice (T cell-deficient mice) simultaneously, which had the same genetic background of C57BL/6. Twelve days later, 5-FU of the minimal dose was given intraperitoneally to treat both the wild type and nude C57BL/6 tumor-bearing mice. The size of tumors in the two different types of mice was observed and recorded. A single dose of 5-FU (75 mg/kg) cured both the EL4 tumor-bearing wild type C57BL/6 mice and the EL4 tumor-bearing nude C57BL/6 mice in the first week. Two weeks after 5-FU treatment, all of the nude mice died of tumor relapse while most of the wild type C57BL/6 mice were fully recovered. A single dose of 5-FU has marked anti-tumor effects on lymphoma EL4 tumor-bearing C57BL/6 mice with or without T lymphocytes. The relapse of tumors after 5-FU treatment might be related to the function of T lymphocytes.

  9. Pretreatment of low dose radiation reduces radiation-induced apoptosis in mouse lymphoma (EL4) cells.

    Science.gov (United States)

    Kim, J H; Hyun, S J; Yoon, M Y; Ji, Y H; Cho, C K; Yoo, S Y

    1997-06-01

    Induction of an adaptive response to ionizing radiation in mouse lymphoma (EL4) cells was studied by using cell survival fraction and apoptotic nucleosomal DNA fragmentation as biological end points. Cells in early log phase were pre-exposed to low dose of gamma-rays (0.01 Gy) 4 or 20 hrs prior to high dose gamma-ray (4, 8 and 12 Gy for cell survival fraction analysis; 8 Gy for DNA fragmentation analysis) irradiation. Then cell survival fractions and the extent of DNA fragmentation were measured. Significant adaptive response, increase in cell survival fraction and decrease in the extent of DNA fragmentation were induced when low and high dose gamma-ray irradiation time interval was 4 hr. Addition of protein or RNA synthesis inhibitor, cycloheximide or 5,6-dichloro-1-beta-d-ribofuranosylbenzimidazole (DRFB), respectively during adaptation period, the period from low dose gamma-ray irradiation to high dose gamma-ray irradiation, was able to inhibit the induction of adaptive response, which is the reduction of the extent DNA fragmentation in irradiated EL4 cells. These data suggest that the induction of adaptive response to ionizing radiation in EL4 cells required both protein and RNA synthesis.

  10. The Mouse Tumor Biology Database: A Comprehensive Resource for Mouse Models of Human Cancer.

    Science.gov (United States)

    Krupke, Debra M; Begley, Dale A; Sundberg, John P; Richardson, Joel E; Neuhauser, Steven B; Bult, Carol J

    2017-11-01

    Research using laboratory mice has led to fundamental insights into the molecular genetic processes that govern cancer initiation, progression, and treatment response. Although thousands of scientific articles have been published about mouse models of human cancer, collating information and data for a specific model is hampered by the fact that many authors do not adhere to existing annotation standards when describing models. The interpretation of experimental results in mouse models can also be confounded when researchers do not factor in the effect of genetic background on tumor biology. The Mouse Tumor Biology (MTB) database is an expertly curated, comprehensive compendium of mouse models of human cancer. Through the enforcement of nomenclature and related annotation standards, MTB supports aggregation of data about a cancer model from diverse sources and assessment of how genetic background of a mouse strain influences the biological properties of a specific tumor type and model utility. Cancer Res; 77(21); e67-70. ©2017 AACR . ©2017 American Association for Cancer Research.

  11. Mouse Models of Gastric Cancer

    Science.gov (United States)

    Hayakawa, Yoku; Fox, James G.; Gonda, Tamas; Worthley, Daniel L.; Muthupalani, Sureshkumar; Wang, Timothy C.

    2013-01-01

    Animal models have greatly enriched our understanding of the molecular mechanisms of numerous types of cancers. Gastric cancer is one of the most common cancers worldwide, with a poor prognosis and high incidence of drug-resistance. However, most inbred strains of mice have proven resistant to gastric carcinogenesis. To establish useful models which mimic human gastric cancer phenotypes, investigators have utilized animals infected with Helicobacter species and treated with carcinogens. In addition, by exploiting genetic engineering, a variety of transgenic and knockout mouse models of gastric cancer have emerged, such as INS-GAS mice and TFF1 knockout mice. Investigators have used the combination of carcinogens and gene alteration to accelerate gastric cancer development, but rarely do mouse models show an aggressive and metastatic gastric cancer phenotype that could be relevant to preclinical studies, which may require more specific targeting of gastric progenitor cells. Here, we review current gastric carcinogenesis mouse models and provide our future perspectives on this field. PMID:24216700

  12. Humanized Mouse Models of Epstein-Barr Virus Infection and Associated Diseases

    Science.gov (United States)

    Fujiwara, Shigeyoshi; Matsuda, Go; Imadome, Ken-Ichi

    2013-01-01

    Epstein-Barr virus (EBV) is a ubiquitous herpesvirus infecting more than 90% of the adult population of the world. EBV is associated with a variety of diseases including infectious mononucleosis, lymphoproliferative diseases, malignancies such as Burkitt lymphoma and nasopharyngeal carcinoma, and autoimmune diseases including rheumatoid arthritis (RA). EBV in nature infects only humans, but in an experimental setting, a limited species of new-world monkeys can be infected with the virus. Small animal models, suitable for evaluation of novel therapeutics and vaccines, have not been available. Humanized mice, defined here as mice harboring functioning human immune system components, are easily infected with EBV that targets cells of the hematoimmune system. Furthermore, humanized mice can mount both cellular and humoral immune responses to EBV. Thus, many aspects of human EBV infection, including associated diseases (e.g., lymphoproliferative disease, hemophagocytic lymphohistiocytosis and erosive arthritis resembling RA), latent infection, and T-cell-mediated and humoral immune responses have been successfully reproduced in humanized mice. Here we summarize recent achievements in the field of humanized mouse models of EBV infection and show how they have been utilized to analyze EBV pathogenesis and normal and aberrant human immune responses to the virus. PMID:25436886

  13. Identification of EBP50 as a Specific Biomarker for Carcinogens Via the Analysis of Mouse Lymphoma Cellular Proteome

    Science.gov (United States)

    Lee, Yoen Jung; Choi, In-Kwon; Sheen, Yhun Yhong; Park, Sue Nie; Kwon, Ho Jeong

    2012-01-01

    To identify specific biomarkers generated upon exposure of L5178Y mouse lymphoma cells to carcinogens, 2-DE and MALDI-TOF MS analysis were conducted using the cellular proteome of L5178Y cells that had been treated with the known carcinogens, 1,2-dibromoethane and O-nitrotoluene and the noncarcinogens, emodin and D-mannitol. Eight protein spots that showed a greater than 1.5-fold increase or decrease in intensity following carcinogen treatment compared with treatment with noncarcinogens were selected. Of the identified proteins, we focused on the candidate biomarker ERM-binding phosphoprotein 50 (EBP50), the expression of which was specifically increased in response to treatment with the carcinogens. The expression level of EBP50 was determined by western analysis using polyclonal rabbit anti-EBP50 antibody. Further, the expression level of EBP50 was increased in cells treated with seven additional carcinogens, verifying that EBP50 could serve as a specific biomarker for carcinogens. PMID:22434383

  14. Lymphoma classification update: B-cell non-Hodgkin lymphomas.

    Science.gov (United States)

    Jiang, Manli; Bennani, N Nora; Feldman, Andrew L

    2017-05-01

    Lymphomas are classified based on the normal counterpart, or cell of origin, from which they arise. Because lymphocytes have physiologic immune functions that vary both by lineage and by stage of differentiation, the classification of lymphomas arising from these normal lymphoid populations is complex. Recent genomic data have contributed additional complexity. Areas covered: Lymphoma classification follows the World Health Organization (WHO) system, which reflects international consensus and is based on pathological, genetic, and clinical factors. A 2016 revision to the WHO classification of lymphoid neoplasms recently was reported. The present review focuses on B-cell non-Hodgkin lymphomas, the most common group of lymphomas, and summarizes recent changes most relevant to hematologists and other clinicians who care for lymphoma patients. Expert commentary: Lymphoma classification is a continually evolving field that needs to be responsive to new clinical, pathological, and molecular understanding of lymphoid neoplasia. Among the entities covered in this review, the 2016 revision of the WHO classification particularly impact the subclassification and genetic stratification of diffuse large B-cell lymphoma and high-grade B-cell lymphomas, and reflect evolving criteria and nomenclature for indolent B-cell lymphomas and lymphoproliferative disorders.

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

    Science.gov (United States)

    2018-04-23

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

  16. Utility of LRF/Pokemon and NOTCH1 protein expression in the distinction between nodular lymphocyte-predominant Hodgkin lymphoma and classical Hodgkin lymphoma.

    Science.gov (United States)

    Bohn, Olga; Maeda, Takahiro; Filatov, Alexander; Lunardi, Andrea; Pandolfi, Pier Paolo; Teruya-Feldstein, Julie

    2014-02-01

    Classical Hodgkin lymphoma (CHL) and nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) are considered separate entities with different prognosis and treatment. However, morphologic features can be similar and immunohistochemical studies are essential in the distinction; thus, determination of additional biomarkers is of utmost importance. LRF/Pokemon is a proto-oncogene, an interacting partner co-expressed with BCL6 in germinal centers and highly expressed in diffuse large B-cell lymphoma and follicular lymphoma. Conversely, loss of the LRF gene in mouse hematopoietic stem cells results in complete block of early B cell development with concomitant Notch de-repression, indicating its critical role in B versus T cell fate decision at the hematopoietic stem cell stage. For the first time, we show that LRF/Pokemon is predominantly expressed in NLPHL cases as is BCL6 with low to absent NOTCH1 protein expression; while Hodgkin Reed-Sternberg (HRS) cells in CHL show low to absent BCL6 and LRF/Pokemon expression with higher NOTCH1 expression. We illustrate a potential functional interaction between LRF and BCL6 in NLPHL pathogenesis, and differential expression of LRF/Pokemon and NOTCH1 proteins in CHL thus showing differential expression, making for an additional diagnostic marker and therapeutic target.

  17. Utility of LRF/Pokemon and NOTCH1 Protein Expression in the Distinction of Nodular Lymphocyte-Predominant Hodgkin Lymphoma and Classical Hodgkin Lymphoma

    Science.gov (United States)

    Bohn, Olga; Maeda, Takahiro; Filatov, Alexander; Lunardi, Andrea; Pandolfi, Pier Paolo; Teruya-Feldstein, Julie

    2014-01-01

    Classical Hodgkin lymphoma (CHL) and nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) are considered separate entities with different prognosis and treatment. However, morphologic features can be similar and immunohistochemical studies are essential in the distinction; thus, determination of additional biomarkers is of utmost importance. LRF/Pokemon is a protooncogene, an interacting partner co-expressed with BCL6 in germinal centers and highly expressed in diffuse large B-cell lymphoma and follicular lymphoma. Conversely, loss of the LRF gene in mouse hematopoietic stem cells results in complete block of early B cell development with concomitant Notch derepression, indicating its critical role in B versus T cell fate decision at the hematopoietic stem cell stage. For the first time, we show that LRF/Pokemon is predominantly expressed in NLPHL cases as is BCL6 with low to absent NOTCH1 protein expression; while Hodgkin Reed-Sternberg (HRS) cells in CHL show low to absent BCL6 and LRF/Pokemon expression with higher NOTCH1 expression. We illustrate a potential functional interaction between LRF and BCL6 in NLPHL pathogenesis, and differential expression of LRF/Pokemon and NOTCH1 proteins in CHL thus showing differential expression, making for an additional diagnostic marker and therapeutic target. PMID:24326827

  18. Deregulated expression of HDAC9 in B cells promotes development of lymphoproliferative disease and lymphoma in mice

    Directory of Open Access Journals (Sweden)

    Veronica S. Gil

    2016-12-01

    Full Text Available Histone deacetylase 9 (HDAC9 is expressed in B cells, and its overexpression has been observed in B-lymphoproliferative disorders, including B-cell non-Hodgkin lymphoma (B-NHL. We examined HDAC9 protein expression and copy number alterations in primary B-NHL samples, identifying high HDAC9 expression among various lymphoma entities and HDAC9 copy number gains in 50% of diffuse large B-cell lymphoma (DLBCL. To study the role of HDAC9 in lymphomagenesis, we generated a genetically engineered mouse (GEM model that constitutively expressed an HDAC9 transgene throughout B-cell development under the control of the immunoglobulin heavy chain (IgH enhancer (Eμ. Here, we report that the Eμ-HDAC9 GEM model develops splenic marginal zone lymphoma and lymphoproliferative disease (LPD with progression towards aggressive DLBCL, with gene expression profiling supporting a germinal center cell origin, as is also seen in human B-NHL tumors. Analysis of Eμ-HDAC9 tumors suggested that HDAC9 might contribute to lymphomagenesis by altering pathways involved in growth and survival, as well as modulating BCL6 activity and p53 tumor suppressor function. Epigenetic modifications play an important role in the germinal center response, and deregulation of the B-cell epigenome as a consequence of mutations and other genomic aberrations are being increasingly recognized as important steps in the pathogenesis of a variety of B-cell lymphomas. A thorough mechanistic understanding of these alterations will inform the use of targeted therapies for these malignancies. These findings strongly suggest a role for HDAC9 in B-NHL and establish a novel GEM model for the study of lymphomagenesis and, potentially, preclinical testing of therapeutic approaches based on histone deacetylase inhibitors.

  19. Lennert's Lymphoma

    International Nuclear Information System (INIS)

    Narayanrao, Suresh T.; Pillai, R.; Nada, Aymen; Hasan, Suhel

    2005-01-01

    Lymphoepithelioid cell lymphoma (Lennert's lymphoma) is a rare morphological variant of peripheral T-cell lymphoma characterized by the presence of numerous clusters of epithelioid histiocytes without formation of discrete granulomas and the intervening atypical lymphocytes. Lennert's lymphoma is often misinterpreted as granulomatous lymphadenitis or Hodgkin's disease. This report describes fine needle aspiration cytology and histological findings in a case of Lennert's lymphoma. (author)

  20. A new immuno- dystrophin-deficient model, the NSG-mdx4Cv mouse, provides evidence for functional improvement following allogeneic satellite cell transplantation

    Science.gov (United States)

    Arpke, Robert W.; Darabi, Radbod; Mader, Tara L.; Zhang, Yu; Toyama, Akira; Lonetree, Cara-lin; Nash, Nardina; Lowe, Dawn A.; Perlingeiro, Rita C.R.; Kyba, Michael

    2013-01-01

    Transplantation of a myogenic cell population into an immunodeficient recipient is an excellent way of assessing the in vivo muscle-generating capacity of that cell population. To facilitate both allogeneic and xenogeneic transplantations of muscle-forming cells in mice we have developed a novel immunodeficient muscular dystrophy model, the NSG-mdx4Cv mouse. The IL2Rg mutation, which is linked to the Dmd gene on the X chromosome, simultaneously depletes NK cells and suppresses thymic lymphomas, issues that limit the utility of the SCID/mdx model. The NSG-mdx4Cv mouse presents a muscular dystrophy of similar severity to the conventional mdx mouse. We show that this animal supports robust engraftment of both pig and dog muscle mononuclear cells. The question of whether satellite cells prospectively isolated by flow cytometry can confer a functional benefit upon transplantation has been controversial. Using allogeneic Pax7-ZsGreen donors and NSG-mdx4Cv recipients, we demonstrate definitively that as few as 900 FACS-isolated satellite cells can provide functional regeneration in vivo, in the form of an increased mean maximal force-generation capacity in cell-transplanted muscles, compared to a sham-injected control group. These studies highlight the potency of satellite cells to improve muscle function, and the utility of the NSG-mdx4Cv model for studies on muscle regeneration and Duchenne muscular dystrophy therapy. PMID:23606600

  1. Transient Responses to NOTCH and TLX1/HOX11 Inhibition in T-Cell Acute Lymphoblastic Leukemia/Lymphoma

    OpenAIRE

    Rakowski, Lesley A.; Lehotzky, Erica A.; Chiang, Mark Y.

    2011-01-01

    To improve the treatment strategies of T-cell acute lymphoblastic leukemia/lymphoma (T-ALL), further efforts are needed to identify therapeutic targets. Dysregulated expression of HOX-type transcription factors occurs in 30-40% of cases of T-ALL. TLX1/HOX11 is the prototypical HOX-type transcription factor. TLX1 may be an attractive therapeutic target because mice that are deficient in TLX1 are healthy. To test this possibility, we developed a conditional doxycycline-regulated mouse model of ...

  2. Mantle Cell Lymphoma

    Science.gov (United States)

    ... Non-Hodgkin Lymphoma Peripheral T-Cell Lymphoma Primary Central Nervous System Lymphoma T-Cell Lymphoma Transformed Mycosis Fungoides Waldenstrom Macroglobulinemia Young Adult Lymphoma Overview Treatment Options Relapsed/Refractory Long-term ...

  3. Marginal Zone Lymphoma

    Science.gov (United States)

    ... Non-Hodgkin Lymphoma Peripheral T-Cell Lymphoma Primary Central Nervous System Lymphoma T-Cell Lymphoma Transformed Mycosis Fungoides Waldenstrom Macroglobulinemia Young Adult Lymphoma Overview Treatment Options Relapsed/Refractory Long-term ...

  4. The second-generation ALK inhibitor alectinib effectively induces apoptosis in human neuroblastoma cells and inhibits tumor growth in a TH-MYCN transgenic neuroblastoma mouse model.

    Science.gov (United States)

    Lu, Jiaxiong; Guan, Shan; Zhao, Yanling; Yu, Yang; Woodfield, Sarah E; Zhang, Huiyuan; Yang, Kristine L; Bieerkehazhi, Shayahati; Qi, Lin; Li, Xiaonan; Gu, Jerry; Xu, Xin; Jin, Jingling; Muscal, Jodi A; Yang, Tianshu; Xu, Guo-Tong; Yang, Jianhua

    2017-08-01

    Activating germline mutations of anaplastic lymphoma kinase (ALK) occur in most cases of hereditary neuroblastoma (NB) and the constitutively active kinase activity of ALK promotes cell proliferation and survival in NB. Therefore, ALK kinase is a potential therapeutic target for NB. In this study, we show that the novel ALK inhibitor alectinib effectively suppressed cell proliferation and induces apoptosis in NB cell lines with either wild-type ALK or mutated ALK (F1174L and D1091N) by blocking ALK-mediated PI3K/Akt/mTOR signaling. In addition, alectinib enhanced doxorubicin-induced cytotoxicity and apoptosis in NB cells. Furthermore, alectinib induced apoptosis in an orthotopic xenograft NB mouse model. Also, in the TH-MYCN transgenic mouse model, alectinib resulted in decreased tumor growth and prolonged survival time. These results indicate that alectinib may be a promising therapeutic agent for the treatment of NB. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Melatonin receptors: latest insights from mouse models

    Science.gov (United States)

    Tosini, Gianluca; Owino, Sharon; Guillame, Jean-Luc; Jockers, Ralf

    2014-01-01

    Summary Melatonin, the neuro-hormone synthesized during the night, has recently seen an unexpected extension of its functional implications towards type 2 diabetes development, visual functions, sleep disturbances and depression. Transgenic mouse models were instrumental for the establishment of the link between melatonin and these major human diseases. Most of the actions of melatonin are mediated by two types of G protein-coupled receptors, named MT1 and MT2, which are expressed in many different organs and tissues. Understanding the pharmacology and function of mouse MT1 and MT2 receptors, including MT1/MT2 heteromers, will be of crucial importance to evaluate the relevance of these mouse models for future therapeutic developments. This review will critically discuss these aspects, and give some perspectives including the generation of new mouse models. PMID:24903552

  6. Systematic analysis of a xenograft mice model for KSHV+ primary effusion lymphoma (PEL.

    Directory of Open Access Journals (Sweden)

    Lu Dai

    Full Text Available Kaposi's sarcoma-associated herpesvirus is the causative agent of primary effusion lymphoma (PEL, which arises preferentially in the setting of infection with human immunodeficiency virus (HIV. Even with standard cytotoxic chemotherapy, PEL continues to cause high mortality rates, requiring the development of novel therapeutic strategies. PEL xenograft models employing immunodeficient mice have been used to study the in vivo effects of a variety of therapeutic approaches. However, it remains unclear whether these xenograft models entirely reflect clinical presentations of KSHV(+ PEL, especially given the recent description of extracavitary solid tumor variants arising in patients. In addition, effusion and solid tumor cells propagated in vivo exhibit unique biology, differing from one another or from their parental cell lines propagated through in vitro culture. Therefore, we used a KSHV(+ PEL/BCBL-1 xenograft model involving non-obese diabetic/severe-combined immunodeficient (NOD/SCID mice, and compared characteristics of effusion and solid tumors with their parent cell culture-derived counterparts. Our results indicate that although this xenograft model can be used for study of effusion and solid lymphoma observed in patients, tumor cells in vivo display unique features to those passed in vitro, including viral lytic gene expression profile, rate of solid tumor development, the host proteins and the complex of tumor microenvironment. These items should be carefully considered when the xenograft model is used for testing novel therapeutic strategies against KSHV-related lymphoma.

  7. Radiation-induced interphase death observed in human T-cell lymphoma cells established as a nude mouse tumor line

    International Nuclear Information System (INIS)

    Igarashi, T.; Yoshida, S.; Miyamoto, T.

    1990-01-01

    Interphase death of cells occurs physiologically in healthy animal tissues as well as in tissues pathologically injured by radiation or drugs. An active self-destruction process has been found to play a major role in the interphase death of highly radiosensitive cells. However, the mechanism of this radiation-induced interphase death in human lymphoma has not yet been studied in detail. In the present study, we examined a lymphoma derived from a child lymphoblastic lymphoma bearing CD1, CD4, and CD8 antigens and established in nude mice. Low-dose x-irradiation of this lymphoma induced interphase cell death with characteristic morphological and biological changes of an active self-destruction process, i.e., changes in cell surface appearance seen using scanning electron microscopy and nuclear fragmentation accompanied with an increase in free DNA. The process was proved to require protein synthesis. It was concluded that the radiosensitivity of this T-cell lymphoma of common thymic type is mainly due to the occurrence of the active self-destruction process

  8. Lymphoma of the eyelid

    DEFF Research Database (Denmark)

    Svendsen, Frederik Holm; Heegaard, Steffen

    2017-01-01

    Lymphoma of the eyelid constitutes 5% of ocular adnexal lymphoma. In previously published cases, 56% of lymphomas of the eyelid are of B-cell origin and 44% are of T-cell origin. The most frequent B-cell lymphomas are extranodal marginal zone lymphoma (27 cases-14%) and diffuse large B......-cell lymphoma (18 cases-9%). T-cell lymphomas are most frequently mycosis fungoides (25 cases-13%), extranodal natural killer/T-cell, nasal-type lymphoma (12 cases-6%), and primary cutaneous anaplastic large-cell lymphoma (12 cases-6%). This distribution differs from the distribution of ocular adnexal lymphoma...... and that of cutaneous lymphoma. The majority of subtypes occur in elderly patients, except for lymphoblastic lymphoma of B-cell and T-cell origin and Burkitt lymphoma, which occur in children and adolescents. Several subtypes have a male predominance, including peripheral T-cell lymphoma and Burkitt lymphoma. Only...

  9. Targetable vulnerabilities in T- and NK-cell lymphomas identified through preclinical models.

    Science.gov (United States)

    Ng, Samuel Y; Yoshida, Noriaki; Christie, Amanda L; Ghandi, Mahmoud; Dharia, Neekesh V; Dempster, Joshua; Murakami, Mark; Shigemori, Kay; Morrow, Sara N; Van Scoyk, Alexandria; Cordero, Nicolas A; Stevenson, Kristen E; Puligandla, Maneka; Haas, Brian; Lo, Christopher; Meyers, Robin; Gao, Galen; Cherniack, Andrew; Louissaint, Abner; Nardi, Valentina; Thorner, Aaron R; Long, Henry; Qiu, Xintao; Morgan, Elizabeth A; Dorfman, David M; Fiore, Danilo; Jang, Julie; Epstein, Alan L; Dogan, Ahmet; Zhang, Yanming; Horwitz, Steven M; Jacobsen, Eric D; Santiago, Solimar; Ren, Jian-Guo; Guerlavais, Vincent; Annis, D Allen; Aivado, Manuel; Saleh, Mansoor N; Mehta, Amitkumar; Tsherniak, Aviad; Root, David; Vazquez, Francisca; Hahn, William C; Inghirami, Giorgio; Aster, Jon C; Weinstock, David M; Koch, Raphael

    2018-05-22

    T- and NK-cell lymphomas (TCL) are a heterogenous group of lymphoid malignancies with poor prognosis. In contrast to B-cell and myeloid malignancies, there are few preclinical models of TCLs, which has hampered the development of effective therapeutics. Here we establish and characterize preclinical models of TCL. We identify multiple vulnerabilities that are targetable with currently available agents (e.g., inhibitors of JAK2 or IKZF1) and demonstrate proof-of-principle for biomarker-driven therapies using patient-derived xenografts (PDXs). We show that MDM2 and MDMX are targetable vulnerabilities within TP53-wild-type TCLs. ALRN-6924, a stapled peptide that blocks interactions between p53 and both MDM2 and MDMX has potent in vitro activity and superior in vivo activity across 8 different PDX models compared to the standard-of-care agent romidepsin. ALRN-6924 induced a complete remission in a patient with TP53-wild-type angioimmunoblastic T-cell lymphoma, demonstrating the potential for rapid translation of discoveries from subtype-specific preclinical models.

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

    Science.gov (United States)

    2018-04-10

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

  11. Rational Design of Mouse Models for Cancer Research

    NARCIS (Netherlands)

    Landgraf, M.; McGovern, J.A.; Friedl, P.; Hutmacher, D.W.

    2018-01-01

    The laboratory mouse is widely considered as a valid and affordable model organism to study human disease. Attempts to improve the relevance of murine models for the investigation of human pathologies led to the development of various genetically engineered, xenograft and humanized mouse models.

  12. Conjunctival Lymphoma

    DEFF Research Database (Denmark)

    Kirkegaard, Marina M; Rasmussen, Peter K; Coupland, Sarah E

    2016-01-01

    IMPORTANCE: To date, the clinical features of the various subtypes of conjunctival lymphoma (CL) have not been previously evaluated in a large cohort. OBJECTIVE: To characterize subtype-specific clinical features of CL and their effect on patient outcome. DESIGN, SETTING, AND PARTICIPANTS...... age was 61.3 years, and 55.1% (145 of 263) were female. All lymphomas were of B-cell type. The most frequent subtype was extranodal marginal zone lymphoma (EMZL) (68.4% [180 of 263]), followed by follicular lymphoma (FL) (16.3% [43 of 263]), mantle cell lymphoma (MCL) (6.8% [18 of 263]), and diffuse...... large B-cell lymphoma (DLBCL) (4.6% [12 of 263). Conjunctival lymphoma commonly manifested in elderly individuals (age range, 60-70 years old), with EMZL having a female predilection (57.8% [104 of 180]) and MCL having a marked male predominance (77.8% [14 of 18]). Unlike EMZL and FL, DLBCL and MCL were...

  13. Mouse models of Fanconi anemia

    International Nuclear Information System (INIS)

    Parmar, Kalindi; D'Andrea, Alan; Niedernhofer, Laura J.

    2009-01-01

    Fanconi anemia is a rare inherited disease characterized by congenital anomalies, growth retardation, aplastic anemia and an increased risk of acute myeloid leukemia and squamous cell carcinomas. The disease is caused by mutation in genes encoding proteins required for the Fanconi anemia pathway, a response mechanism to replicative stress, including that caused by genotoxins that cause DNA interstrand crosslinks. Defects in the Fanconi anemia pathway lead to genomic instability and apoptosis of proliferating cells. To date, 13 complementation groups of Fanconi anemia were identified. Five of these genes have been deleted or mutated in the mouse, as well as a sixth key regulatory gene, to create mouse models of Fanconi anemia. This review summarizes the phenotype of each of the Fanconi anemia mouse models and highlights how genetic and interventional studies using the strains have yielded novel insight into therapeutic strategies for Fanconi anemia and into how the Fanconi anemia pathway protects against genomic instability.

  14. Mouse models of Fanconi anemia

    Energy Technology Data Exchange (ETDEWEB)

    Parmar, Kalindi; D' Andrea, Alan [Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115 (United States); Niedernhofer, Laura J., E-mail: niedernhoferl@upmc.edu [Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine and Cancer Institute, 5117 Centre Avenue, Hillman Cancer Center, Research Pavilion 2.6, Pittsburgh, PA 15213-1863 (United States)

    2009-07-31

    Fanconi anemia is a rare inherited disease characterized by congenital anomalies, growth retardation, aplastic anemia and an increased risk of acute myeloid leukemia and squamous cell carcinomas. The disease is caused by mutation in genes encoding proteins required for the Fanconi anemia pathway, a response mechanism to replicative stress, including that caused by genotoxins that cause DNA interstrand crosslinks. Defects in the Fanconi anemia pathway lead to genomic instability and apoptosis of proliferating cells. To date, 13 complementation groups of Fanconi anemia were identified. Five of these genes have been deleted or mutated in the mouse, as well as a sixth key regulatory gene, to create mouse models of Fanconi anemia. This review summarizes the phenotype of each of the Fanconi anemia mouse models and highlights how genetic and interventional studies using the strains have yielded novel insight into therapeutic strategies for Fanconi anemia and into how the Fanconi anemia pathway protects against genomic instability.

  15. Composite Lymphoma : EBV-positive Classic Hodgkin Lymphoma and Peripheral T-cell Lymphoma A Case Report

    NARCIS (Netherlands)

    Gualco, Gabriela; Chioato, Lucimara; Van Den Berg, Anke; Weiss, Lawrence M.; Bacchi, Carlos E.

    Composite lymphomas are rare and defined as hematopoietic neoplasms with more than I malignant lymphomatous clone showing different phenotypic features. Of all possible combinations between non-Hodgkin lymphomas, B cell or T cell, and Hodgkin lymphoma, the least frequent are the ones combining

  16. Genome-Derived Cytosolic DNA Mediates Type I Interferon-Dependent Rejection of B Cell Lymphoma Cells

    Directory of Open Access Journals (Sweden)

    Yu J. Shen

    2015-04-01

    Full Text Available The DNA damage response (DDR induces the expression of type I interferons (IFNs, but the underlying mechanisms are poorly understood. Here, we show the presence of cytosolic DNA in different mouse and human tumor cells. Treatment of cells with genotoxic agents increased the levels of cytosolic DNA in a DDR-dependent manner. Cloning of cytosolic DNA molecules from mouse lymphoma cells suggests that cytosolic DNA is derived from unique genomic loci and has the potential to form non-B DNA structures, including R-loops. Overexpression of Rnaseh1, which resolves R-loops, reduced the levels of cytosolic DNA, type I Ifn transcripts, and type I IFN-dependent rejection of lymphoma cells. Live-cell imaging showed a dynamic contact of cytosolic DNA with mitochondria, an important organelle for innate immune recognition of cytosolic nucleotides. In summary, we found that cytosolic DNA is present in many tumor cells and contributes to the immunogenicity of tumor cells.

  17. Peripheral T-Cell Lymphoma

    Science.gov (United States)

    ... Non-Hodgkin Lymphoma Peripheral T-Cell Lymphoma Primary Central Nervous System Lymphoma T-Cell Lymphoma Transformed Mycosis Fungoides Waldenstrom Macroglobulinemia Young Adult Lymphoma Overview Treatment Options Relapsed/Refractory Long-term ...

  18. Angioimmunoblastic T-Cell Lymphoma

    Science.gov (United States)

    ... Non-Hodgkin Lymphoma Peripheral T-Cell Lymphoma Primary Central Nervous System Lymphoma T-Cell Lymphoma Transformed Mycosis Fungoides Waldenstrom Macroglobulinemia Young Adult Lymphoma Overview Treatment Options Relapsed/Refractory Long-term ...

  19. Anaplastic Large Cell Lymphoma

    Science.gov (United States)

    ... Non-Hodgkin Lymphoma Peripheral T-Cell Lymphoma Primary Central Nervous System Lymphoma T-Cell Lymphoma Transformed Mycosis Fungoides Waldenstrom Macroglobulinemia Young Adult Lymphoma Overview Treatment Options Relapsed/Refractory Long-term ...

  20. Vorinostat, Rituximab, Ifosfamide, Carboplatin, and Etoposide in Treating Patients With Relapsed or Refractory Lymphoma or Previously Untreated T-Cell Non-Hodgkin Lymphoma or Mantle Cell Lymphoma

    Science.gov (United States)

    2017-04-17

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage I Mantle Cell Lymphoma; Stage I Mycosis Fungoides/Sezary Syndrome; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage II Mycosis Fungoides/Sezary Syndrome; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome; Waldenström Macroglobulinemia

  1. Malignant lymphoma of the conjunctiva

    DEFF Research Database (Denmark)

    Kirkegaard, Marina M.; Coupland, Sarah E.; Prause, Jan U.

    2015-01-01

    Conjunctival lymphomas constitute 25% of all ocular adnexal lymphomas. The majority are B-cell non-Hodgkin lymphomas (NHLs) (98%), whereas conjunctival T-cell NHLs are rare (2%). The most frequent subtype of conjunctival B-cell lymphoma is extranodal marginal zone lymphoma (EMZL; 81%), followed...... by follicular lymphoma (8%), diffuse large B-cell lymphoma (3%), and mantle cell lymphoma (3%). Extranodal marginal zone lymphoma occurs slightly more often in women and, along with follicular lymphoma, presents late in the seventh decade of life, whereas diffuse large B-cell lymphoma and especially mantle cell...... lymphoma have a predilection for the male gender and typically present in the eighth decade. Extranodal marginal zone lymphoma and follicular lymphoma present most frequently in the forniceal and bulbar conjunctiva. Conjunctival diffuse large B-cell lymphoma, mantle cell lymphoma and T-cell NHLs...

  2. The Mouse Genome Database (MGD): facilitating mouse as a model for human biology and disease.

    Science.gov (United States)

    Eppig, Janan T; Blake, Judith A; Bult, Carol J; Kadin, James A; Richardson, Joel E

    2015-01-01

    The Mouse Genome Database (MGD, http://www.informatics.jax.org) serves the international biomedical research community as the central resource for integrated genomic, genetic and biological data on the laboratory mouse. To facilitate use of mouse as a model in translational studies, MGD maintains a core of high-quality curated data and integrates experimentally and computationally generated data sets. MGD maintains a unified catalog of genes and genome features, including functional RNAs, QTL and phenotypic loci. MGD curates and provides functional and phenotype annotations for mouse genes using the Gene Ontology and Mammalian Phenotype Ontology. MGD integrates phenotype data and associates mouse genotypes to human diseases, providing critical mouse-human relationships and access to repositories holding mouse models. MGD is the authoritative source of nomenclature for genes, genome features, alleles and strains following guidelines of the International Committee on Standardized Genetic Nomenclature for Mice. A new addition to MGD, the Human-Mouse: Disease Connection, allows users to explore gene-phenotype-disease relationships between human and mouse. MGD has also updated search paradigms for phenotypic allele attributes, incorporated incidental mutation data, added a module for display and exploration of genes and microRNA interactions and adopted the JBrowse genome browser. MGD resources are freely available to the scientific community. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  3. The wobbler mouse, an ALS animal model

    DEFF Research Database (Denmark)

    Moser, Jakob Maximilian; Bigini, Paolo; Schmitt-John, Thomas

    2013-01-01

    This review article is focused on the research progress made utilizing the wobbler mouse as animal model for human motor neuron diseases, especially the amyotrophic lateral sclerosis (ALS). The wobbler mouse develops progressive degeneration of upper and lower motor neurons and shows striking...

  4. Composite lymphoma: Mycosis fungoides with hodgkin′s lymphoma

    Directory of Open Access Journals (Sweden)

    Mehta Jalpa

    2005-01-01

    Full Text Available Mycosis fungoides (MF is a malignant lymphoma, primarily of the skin and is characterized by infiltration of the skin by atypical T-cells which have a tendency for epidermotropism. Hodgkins disease (HD is considered to be a malignant lymphoma affecting predominantly the lymph nodes and characterized by presence of Reed- Sternberg cells on histopathology, though, the exact origin of the Reed Sternberg cell and the nature of the malignant cell is not known yet. Few cases of association of mycosis fungoides with Hodgkin′s lymphoma have been reported in the literature. It was reported in the past that when mycosis fungoides spreads to the lymph nodes and other viscera it frequently gets transformed into a more common lymphoma like Hodgkin′s lymphoma. However it has now been proved that the two malignancies are distinct and that such patients probably have a tumour diathesis.

  5. Mutation induction in a mouse lymphoma cell mutant sensitive to 4-nitroquinoline 1-oxide and ultraviolet radiation

    International Nuclear Information System (INIS)

    Sato, K.; Hieda, N.

    1980-01-01

    The mutant mouse lymphoma cell Q31, which is sensitive to 4-nitroquinoline 1-oxide and ultraviolet radiation (UV), was compared with the parental L5178Y cell for the effect of caffeine and mutation induction after UV irradiation. Caffeine potentiated the lethal effect of UV in both cell strains to a similar extent, indicating that the defective process in Q31 cells was caffeine-insensitive. UV-induced mutation to 6-thioguanine resistance was determined in L5178Y and Q31 cells. The maximal yield of mutants was obtained 7 days post-irradiation in L5178Y cells and 14 days in Q31 cells for higher UV doses. It appears that a much longer time is required for the mutant cells than for the parental cells for full expression of the resistance phenotype even at equitoxic UV doses. A substantially higher frequency in induced mutations was observed in Q31 cells than in L5178Y cells at a given dose of UV. A plot of induced mutation frequency as a function of logarithm of surviving fraction again indicates hypermutability of Q31 cells as compared with the parental strain. In contrast, X-rays induced a similar frequency of mutations to 6-thioguanine resistance in L5178Y and Q31 cells. (orig.)

  6. Regulation of Id2 expression in EL4 T lymphoma cells overexpressing growth hormone.

    Science.gov (United States)

    Weigent, Douglas A

    2009-01-01

    In previous studies, we have shown that overexpression of growth hormone (GH) in cells of the immune system upregulates proteins involved in cell growth and protects from apoptosis. Here, we report that overexpression of GH in EL4 T lymphoma cells (GHo) also significantly increased levels of the inhibitor of differentiation-2 (Id2). The increase in Id2 was suggested in both Id2 promoter luciferase assays and by Western analysis for Id2 protein. To identify the regulatory elements that mediate transcriptional activation by GH in the Id2 promoter, promoter deletion analysis was performed. Deletion analysis revealed that transactivation involved a 301-132bp region upstream to the Id2 transcriptional start site. The pattern in the human GHo Jurkat T lymphoma cell line paralleled that found in the mouse GHo EL4 T lymphoma cell line. Significantly less Id2 was detected in the nucleus of GHo EL4 T lymphoma cells compared to vector alone controls. Although serum increased the levels of Id2 in control vector alone cells, no difference was found in the total levels of Id2 in GHo EL4 T lymphoma cells treated with or without serum. The increase in Id2 expression in GHo EL4 T lymphoma cells measured by Id2 promoter luciferase expression and Western blot analysis was blocked by the overexpression of a dominant-negative mutant of STAT5. The results suggest that in EL4 T lymphoma cells overexpressing GH, there is an upregulation of Id2 protein that appears to involve STAT protein activity.

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

    Directory of Open Access Journals (Sweden)

    Daisuke Usuda

    2017-11-01

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

  8. Dynamic mathematical modeling of IL13-induced signaling in Hodgkin and primary mediastinal B-cell lymphoma allows prediction of therapeutic targets.

    Science.gov (United States)

    Raia, Valentina; Schilling, Marcel; Böhm, Martin; Hahn, Bettina; Kowarsch, Andreas; Raue, Andreas; Sticht, Carsten; Bohl, Sebastian; Saile, Maria; Möller, Peter; Gretz, Norbert; Timmer, Jens; Theis, Fabian; Lehmann, Wolf-Dieter; Lichter, Peter; Klingmüller, Ursula

    2011-02-01

    Primary mediastinal B-cell lymphoma (PMBL) and classical Hodgkin lymphoma (cHL) share a frequent constitutive activation of JAK (Janus kinase)/STAT signaling pathway. Because of complex, nonlinear relations within the pathway, key dynamic properties remained to be identified to predict possible strategies for intervention. We report the development of dynamic pathway models based on quantitative data collected on signaling components of JAK/STAT pathway in two lymphoma-derived cell lines, MedB-1 and L1236, representative of PMBL and cHL, respectively. We show that the amounts of STAT5 and STAT6 are higher whereas those of SHP1 are lower in the two lymphoma cell lines than in normal B cells. Distinctively, L1236 cells harbor more JAK2 and less SHP1 molecules per cell than MedB-1 or control cells. In both lymphoma cell lines, we observe interleukin-13 (IL13)-induced activation of IL4 receptor α, JAK2, and STAT5, but not of STAT6. Genome-wide, 11 early and 16 sustained genes are upregulated by IL13 in both lymphoma cell lines. Specifically, the known STAT-inducible negative regulators CISH and SOCS3 are upregulated within 2 hours in MedB-1 but not in L1236 cells. On the basis of this detailed quantitative information, we established two mathematical models, MedB-1 and L1236 model, able to describe the respective experimental data. Most of the model parameters are identifiable and therefore the models are predictive. Sensitivity analysis of the model identifies six possible therapeutic targets able to reduce gene expression levels in L1236 cells and three in MedB-1. We experimentally confirm reduction in target gene expression in response to inhibition of STAT5 phosphorylation, thereby validating one of the predicted targets.

  9. SEPTIN2 and STATHMIN Regulate CD99-Mediated Cellular Differentiation in Hodgkin's Lymphoma.

    Directory of Open Access Journals (Sweden)

    Wenjing Jian

    Full Text Available Hodgkin's lymphoma (HL is a lymphoid neoplasm characterized by Hodgkin's and Reed-Sternberg (H/RS cells, which is regulated by CD99. We previously reported that CD99 downregulation led to the transformation of murine B lymphoma cells (A20 into cells with an H/RS phenotype, while CD99 upregulation induced differentiation of classical Hodgkin's lymphoma (cHL cells (L428 into terminal B-cells. However, the molecular mechanism remains unclear. In this study, using fluorescence two-dimensional differential in-gel electrophoresis and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS, we have analyzed the alteration of protein expression following CD99 upregulation in L428 cells as well as downregulation of mouse CD99 antigen-like 2 (mCD99L2 in A20 cells. Bioinformatics analysis showed that SEPTIN2 and STATHMIN, which are cytoskeleton proteins, were significantly differentially expressed, and chosen for further validation and functional analysis. Differential expression of SEPTIN2 was found in both models and was inversely correlated with CD99 expression. STATHMIN was identified in the A20 cell line model and its expression was positively correlated with that of CD99. Importantly, silencing of SEPTIN2 with siRNA substantially altered the cellular cytoskeleton in L428 cells. The downregulation of STATHMIN by siRNA promoted the differentiation of H/RS cells toward terminal B-cells. These results suggest that SEPTIN2-mediated cytoskeletal rearrangement and STATHMIN-mediated differentiation may contribute to changes in cell morphology and differentiation of H/RS cells with CD99 upregulation in HL.

  10. Mouse Models of the Skin: Models to Define Mechanisms of Skin Carcinogenesis

    International Nuclear Information System (INIS)

    Wheeler, D. L.; Verma, A. K.; Denning, M. F.

    2013-01-01

    The multistep model of mouse skin carcinogenesis has facilitated identification of irreversible genetic events of initiation and progression, and epigenetic events of tumor promotion. Mouse skin tumor initiation can be accomplished by a single exposure to a sufficiently small dose of a carcinogen, and this step is rapid and irreversible. However, promotion of skin tumor formation requires a repeated and prolonged exposure to a promoter, and that tumor promotion is reversible. Investigations focused on the mechanisms of mouse carcinogenesis have resulted in the identifications of potential molecular targets of cancer induction and progression useful in planning strategies for human cancer prevention trials. This special issue contains eight papers that focus on mouse models used to study individual proteins expressed in the mouse skin and the role they play in differentiation, tissue homeostasis, skin carcinogenesis, and chemo prevention of skin cancer.

  11. A Humanized Mouse Model Generated Using Surplus Neonatal Tissue

    Directory of Open Access Journals (Sweden)

    Matthew E. Brown

    2018-04-01

    Full Text Available Summary: Here, we describe the NeoThy humanized mouse model created using non-fetal human tissue sources, cryopreserved neonatal thymus and umbilical cord blood hematopoietic stem cells (HSCs. Conventional humanized mouse models are made by engrafting human fetal thymus and HSCs into immunocompromised mice. These mice harbor functional human T cells that have matured in the presence of human self-peptides and human leukocyte antigen molecules. Neonatal thymus tissue is more abundant and developmentally mature and allows for creation of up to ∼50-fold more mice per donor compared with fetal tissue models. The NeoThy has equivalent frequencies of engrafted human immune cells compared with fetal tissue humanized mice and exhibits T cell function in assays of ex vivo cell proliferation, interferon γ secretion, and in vivo graft infiltration. The NeoThy model may provide significant advantages for induced pluripotent stem cell immunogenicity studies, while bypassing the requirement for fetal tissue. : Corresponding author William Burlingham and colleagues created a humanized mouse model called the NeoThy. The NeoThy uses human neonatal, rather than fetal, tissue sources for generating a human immune system within immunocompromised mouse hosts. NeoThy mice are an attractive alternative to conventional humanized mouse models, as they enable robust and reproducible iPSC immunogenicity experiments in vivo. Keywords: NeoThy, humanized mouse, iPSC, PSC, immunogenicity, transplantation, immunology, hematopoietic stem cells, induced pluripotent stem cells, thymus

  12. Activity of the novel BCR kinase inhibitor IQS019 in preclinical models of B-cell non-Hodgkin lymphoma

    Directory of Open Access Journals (Sweden)

    P. Balsas

    2017-03-01

    Full Text Available Abstract Background Pharmacological inhibition of B cell receptor (BCR signaling has recently emerged as an effective approach in a wide range of B lymphoid neoplasms. However, despite promising clinical activity of the first Bruton’s kinase (Btk and spleen tyrosine kinase (Syk inhibitors, a small fraction of patients tend to develop progressive disease after initial response to these agents. Methods We evaluated the antitumor activity of IQS019, a new BCR kinase inhibitor with increased affinity for Btk, Syk, and Lck/Yes novel tyrosine kinase (Lyn, in a set of 34 B lymphoid cell lines and primary cultures, including samples with acquired resistance to the first-in-class Btk inhibitor ibrutinib. Safety and efficacy of the compound were then evaluated in two xenograft mouse models of B cell lymphoma. Results IQS019 simultaneously engaged a rapid and dose-dependent de-phosphorylation of both constitutive and IgM-activated Syk, Lyn, and Btk, leading to impaired cell proliferation, reduced CXCL12-dependent cell migration, and induction of caspase-dependent apoptosis. Accordingly, B cell lymphoma-bearing mice receiving IQS019 presented a reduced tumor outgrowth characterized by a decreased mitotic index and a lower infiltration of malignant cells in the spleen, in tight correlation with downregulation of phospho-Syk, phospho-Lyn, and phospho-Btk. More interestingly, IQS019 showed improved efficacy in vitro and in vivo when compared to the first-in-class Btk inhibitor ibrutinib, and was active in cells with acquired resistance to this latest. Conclusions These results define IQS019 as a potential drug candidate for a variety of B lymphoid neoplasms, including cases with acquired resistance to current BCR-targeting therapies.

  13. Authentication of Primordial Characteristics of the CLBL-1 Cell Line Prove the Integrity of a Canine B-Cell Lymphoma in a Murine In Vivo Model

    OpenAIRE

    Rütgen, Barbara C.; Willenbrock, Saskia; Reimann-Berg, Nicola; Walter, Ingrid; Fuchs-Baumgartinger, Andrea; Wagner, Siegfried; Kovacic, Boris; Essler, Sabine E.; Schwendenwein, Ilse; Nolte, Ingo; Saalmüller, Armin; Escobar, Hugo Murua

    2012-01-01

    Cell lines are key tools in cancer research allowing the generation of neoplasias in animal models resembling the initial tumours able to mimic the original neoplasias closely in vivo. Canine lymphoma is the major hematopoietic malignancy in dogs and considered as a valuable spontaneous large animal model for human Non-Hodgkin's Lymphoma (NHL). Herein we describe the establishment and characterisation of an in vivo model using the canine B-cell lymphoma cell line CLBL-1 analysing the stabilit...

  14. Primary lymphoma of the brain

    Science.gov (United States)

    Brain lymphoma; Cerebral lymphoma; Primary lymphoma of the central nervous system; Lymphoma - brain ... The cause of primary brain lymphoma is not known. People with a weakened immune system are at high risk for primary lymphoma of the brain. ...

  15. Biphasic Rapamycin Effects in Lymphoma and Carcinoma Treatment.

    Science.gov (United States)

    Liu, Yang; Pandeswara, Srilakshmi; Dao, Vinh; Padrón, Álvaro; Drerup, Justin M; Lao, Shunhua; Liu, Aijie; Hurez, Vincent; Curiel, Tyler J

    2017-01-15

    mTOR drives tumor growth but also supports T-cell function, rendering the applications of mTOR inhibitors complex especially in T-cell malignancies. Here, we studied the effects of the mTOR inhibitor rapamycin in mouse EL4 T-cell lymphoma. Typical pharmacologic rapamycin (1-8 mg/kg) significantly reduced tumor burden via direct suppression of tumor cell proliferation and improved survival in EL4 challenge independent of antitumor immunity. Denileukin diftitox (DD)-mediated depletion of regulatory T cells significantly slowed EL4 growth in vivo in a T-cell-dependent fashion. However, typical rapamycin inhibited T-cell activation and tumor infiltration in vivo and failed to boost DD treatment effects. Low-dose (LD) rapamycin (75 μg/kg) increased potentially beneficial CD44hiCD62L + CD8 + central memory T cells in EL4 challenge, but without clinical benefit. LD rapamycin significantly enhanced DD treatment efficacy, but DD plus LD rapamycin treatment effects were independent of antitumor immunity. Instead, rapamycin upregulated EL4 IL2 receptor in vitro and in vivo, facilitating direct DD tumor cell killing. LD rapamycin augmented DD efficacy against B16 melanoma and a human B-cell lymphoma, but not against human Jurkat T-cell lymphoma or ID8agg ovarian cancer cells. Treatment effects correlated with IL2R expression, but mechanisms in some tumors were not fully defined. Overall, our data define a distinct, biphasic mechanisms of action of mTOR inhibition at doses that are clinically exploitable, including in T-cell lymphomas. Cancer Res; 77(2); 520-31. ©2016 AACR. ©2016 American Association for Cancer Research.

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

    NARCIS (Netherlands)

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

    1999-01-01

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

  17. The B-cell receptor controls fitness of MYC-driven lymphoma cells via GSK3β inhibition.

    Science.gov (United States)

    Varano, Gabriele; Raffel, Simon; Sormani, Martina; Zanardi, Federica; Lonardi, Silvia; Zasada, Christin; Perucho, Laura; Petrocelli, Valentina; Haake, Andrea; Lee, Albert K; Bugatti, Mattia; Paul, Ulrike; Van Anken, Eelco; Pasqualucci, Laura; Rabadan, Raul; Siebert, Reiner; Kempa, Stefan; Ponzoni, Maurilio; Facchetti, Fabio; Rajewsky, Klaus; Casola, Stefano

    2017-06-08

    Similar to resting mature B cells, where the B-cell antigen receptor (BCR) controls cellular survival, surface BCR expression is conserved in most mature B-cell lymphomas. The identification of activating BCR mutations and the growth disadvantage upon BCR knockdown of cells of certain lymphoma entities has led to the view that BCR signalling is required for tumour cell survival. Consequently, the BCR signalling machinery has become an established target in the therapy of B-cell malignancies. Here we study the effects of BCR ablation on MYC-driven mouse B-cell lymphomas and compare them with observations in human Burkitt lymphoma. Whereas BCR ablation does not, per se, significantly affect lymphoma growth, BCR-negative (BCR - ) tumour cells rapidly disappear in the presence of their BCR-expressing (BCR + ) counterparts in vitro and in vivo. This requires neither cellular contact nor factors released by BCR + tumour cells. Instead, BCR loss induces the rewiring of central carbon metabolism, increasing the sensitivity of receptor-less lymphoma cells to nutrient restriction. The BCR attenuates glycogen synthase kinase 3 beta (GSK3β) activity to support MYC-controlled gene expression. BCR - tumour cells exhibit increased GSK3β activity and are rescued from their competitive growth disadvantage by GSK3β inhibition. BCR - lymphoma variants that restore competitive fitness normalize GSK3β activity after constitutive activation of the MAPK pathway, commonly through Ras mutations. Similarly, in Burkitt lymphoma, activating RAS mutations may propagate immunoglobulin-crippled tumour cells, which usually represent a minority of the tumour bulk. Thus, while BCR expression enhances lymphoma cell fitness, BCR-targeted therapies may profit from combinations with drugs targeting BCR - tumour cells.

  18. Behavioral phenotypes of genetic mouse models of autism.

    Science.gov (United States)

    Kazdoba, T M; Leach, P T; Crawley, J N

    2016-01-01

    More than a hundred de novo single gene mutations and copy-number variants have been implicated in autism, each occurring in a small subset of cases. Mutant mouse models with syntenic mutations offer research tools to gain an understanding of the role of each gene in modulating biological and behavioral phenotypes relevant to autism. Knockout, knockin and transgenic mice incorporating risk gene mutations detected in autism spectrum disorder and comorbid neurodevelopmental disorders are now widely available. At present, autism spectrum disorder is diagnosed solely by behavioral criteria. We developed a constellation of mouse behavioral assays designed to maximize face validity to the types of social deficits and repetitive behaviors that are central to an autism diagnosis. Mouse behavioral assays for associated symptoms of autism, which include cognitive inflexibility, anxiety, hyperactivity, and unusual reactivity to sensory stimuli, are frequently included in the phenotypic analyses. Over the past 10 years, we and many other laboratories around the world have employed these and additional behavioral tests to phenotype a large number of mutant mouse models of autism. In this review, we highlight mouse models with mutations in genes that have been identified as risk genes for autism, which work through synaptic mechanisms and through the mTOR signaling pathway. Robust, replicated autism-relevant behavioral outcomes in a genetic mouse model lend credence to a causal role for specific gene contributions and downstream biological mechanisms in the etiology of autism. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  19. Hodgkin lymphoma - children

    Science.gov (United States)

    ... families share common experiences may help ease your stress. American Childhood Cancer Organization - www.acco.org Leukemia and ... Cancer - Hodgkin lymphoma - children; Childhood Hodgkin lymphoma ... Cancer Institute website. Childhood Hodgkin lymphoma treatment (PDQ) - health professional ...

  20. Induction of DNA breakage in X-irradiated nucleoids selectively stripped of nuclear proteins in two mouse lymphoma cell lines differing in radiosensitivity

    International Nuclear Information System (INIS)

    Kruszewski, M.; Iwanenko, T.

    1998-01-01

    The role of nuclear proteins in protection of DNA against ionizing radiation and their contribution to the radiation sensitivity was examined by an alkaline version of comet assay in two L5178Y (LY) mouse lymphoma cell lines differing in sensitivity t o ionizing radiation. LY-S cells are twice more sensitive to ionizing radiation than LY-R cells (D 0 values of survival curves are 0.5 Gy and 1 Gy, respectively). Sequential removal of nuclear proteins by extraction with NaCl of different concentrations increased the X-ray induced DNA damage in LY-R nucleoids. In contrast, in the radiation sensitive LY-S cell line, depletion of nuclear proteins practically did not affect DNA damage. Although there is no doubt that the main cause of LY-S cells' sensitivity to ionizing radiation is a defect in the repair of double-strand breaks, our data support the concept that nuclear matrix organization may contribute to the cellular susceptibility to DNA damaging agents. (author)

  1. A novel, long-lived, and highly engraftable immunodeficient mouse model of mucopolysaccharidosis type I

    Directory of Open Access Journals (Sweden)

    Daniel C Mendez

    Full Text Available Mucopolysaccharidosis type I (MPS I is an inherited α-L-iduronidase (IDUA, I deficiency in which glycosaminoglycan (GAG accumulation causes progressive multisystem organ dysfunction, neurological impairment, and death. Current MPS I mouse models, based on a NOD/SCID (NS background, are short-lived, providing a very narrow window to assess the long-term efficacy of therapeutic interventions. They also develop thymic lymphomas, making the assessment of potential tumorigenicity of human stem cell transplantation problematic. We therefore developed a new MPS I model based on a NOD/SCID/Il2rγ (NSG background. This model lives longer than 1 year and is tumor-free during that time. NSG MPS I (NSGI mice exhibit the typical phenotypic features of MPS I including coarsened fur and facial features, reduced/abnormal gait, kyphosis, and corneal clouding. IDUA is undetectable in all tissues examined while GAG levels are dramatically higher in most tissues. NSGI brain shows a significant inflammatory response and prominent gliosis. Neurological MPS I manifestations are evidenced by impaired performance in behavioral tests. Human neural and hematopoietic stem cells were found to readily engraft, with human cells detectable for at least 1 year posttransplantation. This new MPS I model is thus suitable for preclinical testing of novel pluripotent stem cell-based therapy approaches.

  2. Lymphoma of the Eyelid

    DEFF Research Database (Denmark)

    Svendsen, Frederik Holm; Rasmussen, Peter Kristian; Coupland, Sarah E.

    2017-01-01

    Purpose To document subtype-specific clinical features of lymphoma of the eyelid, and their effect on patient outcome. Design Retrospective observational case series. Methods Patient data were collected from 7 international eye cancer centers from January 1, 1980 through December 31, 2015....... The cases included primary and secondary lymphomas affecting the eyelid. Overall survival, disease-specific survival (DSS), and progression-free survival were the primary endpoints. Results Eighty-six patients were included. Mean age was 63 years and 47 (55%) were male. Non-Hodgkin B-cell lymphomas...... constituted 83% (n = 71) and T-cell lymphomas constituted 17% (n = 15). The most common subtypes were extranodal marginal-zone lymphoma (EMZL) (37% [n = 32]), follicular lymphoma (FL) (23% [n = 20]), diffuse large B-cell lymphoma (DLBCL) (10% [n = 9]), mantle cell lymphoma (MCL) (8% [n = 7]), and mycosis...

  3. Mantle-cell lymphoma.

    Science.gov (United States)

    Barista, I; Romaguera, J E; Cabanillas, F

    2001-03-01

    During the past decade, mantle-cell lymphoma has been established as a new disease entity. The normal counterparts of the cells forming this malignant lymphoma are found in the mantle zone of the lymph node, a thin layer surrounding the germinal follicles. These cells have small to medium-sized nuclei, are commonly indented or cleaved, and stain positively with CD5, CD20, cyclin D1, and FMC7 antibodies. Because of its morphological appearance and a resemblance to other low-grade lymphomas, many of which grow slowly, this lymphoma was initially thought to be an indolent tumour, but its natural course was not thoroughly investigated until the 1990s, when the BCL1 oncogene was identified as a marker for this disease. Mantle-cell lymphoma is a discrete entity, unrelated to small lymphocytic or small-cleaved-cell lymphomas.

  4. Transformation of marginal zone lymphoma (and association with other lymphomas).

    Science.gov (United States)

    Casulo, Carla; Friedberg, Jonathan

    Marginal zone lymphomas (MZL) are a diverse group of indolent lymphoproliferative disorders that comprise three subtypes: nodal, splenic and mucosal associated marginal zone lymphomas (MALT). Histologic transformation (HT) to an aggressive lymphoma is a rare event that can occur in any subtype, and at lower frequency compared to other indolent non Hodgkin lymphomas (NHL) like follicular lymphoma. There are few data directly associated with risk and prognosis of transformation in MZL. However, recent advances in the understanding of molecular and genetic features of MALT have contributed to an evolving appreciation of HT in this disease. Optimal treatment of HT of MZL remains unknown. Much of the approach to managing transformed MZL is extrapolated from other indolent NHLs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Adult T-Cell Leukemia/Lymphoma

    Science.gov (United States)

    ... Non-Hodgkin Lymphoma Peripheral T-Cell Lymphoma Primary Central Nervous System Lymphoma T-Cell Lymphoma Transformed Mycosis Fungoides Waldenstrom Macroglobulinemia Young Adult Lymphoma Overview Treatment Options Relapsed/Refractory Long-term ...

  6. Serenoa repens extracts promote hair regeneration and repair of hair loss mouse models by activating TGF-β and mitochondrial signaling pathway.

    Science.gov (United States)

    Zhu, H-L; Gao, Y-H; Yang, J-Q; Li, J-B; Gao, J

    2018-06-01

    Plenty of plant extracts have been used for treating hair loss. This study aims to investigate the effects of liposterolic extracts of Serenoa repens (LSESr) on hair cell growth and regeneration of hair, and clarify the associated mechanisms. Human keratinocyte cells (HACAT) were cultured, incubated with dihydrotestosterone (DHT) and treated with LSESr. Cell viability was examined by using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H- tetrazolium bromide (MTT) assay. Hair loss C57BL/6 mouse model was established by inducing with DHT. Hair growth, density, and thickness were evaluated. Back skin samples were collected and stained with hematoxylin and eosin (HE) assay. B-cell lymphoma-2 (Bcl-2), Bcl-2 associated protein X (Bax), cleaved caspase 3 and transforming growth factor β2 (TGF-β2) were examined using Western blot assay. LSESr treatment significantly increased HACAT cell viabilities compared to DHT-only treated cells (p<0.05). LSESr treatment post injection of DHT significantly converted skin color from pink to gray and increased hair density, weight and thickness compared to DHT-only treated mice (p<0.05). LSESr treatment significantly triggered follicle growth and decreased inflammatory response. LSESr treatment significantly decreased TGF-β2 and cleaved caspase 3 expression of hair loss mouse models compared to that of DHT treated mice (p<0.05). LSESr treatment significantly enhanced Bcl-2 expression and reduced Bax expression compared to that of DHT treated mice (p<0.05). Meanwhile, effects of LSESr were substantial even achieving to the potential of finasteride. LSESr promoted the hair regeneration and repair of hair loss mouse models by activating TGF-β signaling and mitochondrial signaling pathway.

  7. Gastric Lymphoma with Secondary Trigeminal Nerve Lymphoma: A Case Report

    Directory of Open Access Journals (Sweden)

    Warissara Rongthong

    2017-05-01

    Full Text Available Data supporting the role of radiotherapy in secondary trigeminal nerve lymphoma is scarce. Here, I report the case of 64-year-old Thai male diagnosed as gastric diffuse large B cell lymphoma with secondary trigeminal nerve lymphoma. He had previously received one cycle of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP, followed by five cycles of rituximab plus CHOP (R-CHOP with intrathecal methotrexate (MTX and cytarabine (Ara-C. One month after the last cycle of R-CHOP, he developed a headache and numbness on the left side of his face. MRI revealed thickening of the left trigeminal nerve. He received one intrathecal injection of MTX and Ara-C, followed by systemic chemotherapy. After receiving intrathecal chemotherapy, his symptoms disappeared. Clinical response and MRI studies suggested secondary trigeminal nerve lymphoma. Two months later, our patient’s secondary trigeminal nerve lymphoma had progressed. Salvage whole brain irradiation (36 Gy with boost dose (50 Gy along the left trigeminal nerve was given. Unfortunately, our patient developed heart failure and expired during the radiotherapy session. In conclusion and specific to secondary central nervous system lymphoma (SCNSL, radiotherapy may benefit patients who fail to respond to systemic chemotherapy and palliative treatment. The results this report fail to support the role of radiotherapy in secondary trigeminal nerve lymphoma.

  8. Mouse model for acute Epstein-Barr virus infection.

    Science.gov (United States)

    Wirtz, Tristan; Weber, Timm; Kracker, Sven; Sommermann, Thomas; Rajewsky, Klaus; Yasuda, Tomoharu

    2016-11-29

    Epstein-Barr Virus (EBV) infects human B cells and drives them into continuous proliferation. Two key viral factors in this process are the latent membrane proteins LMP1 and LMP2A, which mimic constitutively activated CD40 receptor and B-cell receptor signaling, respectively. EBV-infected B cells elicit a powerful T-cell response that clears the infected B cells and leads to life-long immunity. Insufficient immune surveillance of EBV-infected B cells causes life-threatening lymphoproliferative disorders, including mostly germinal center (GC)-derived B-cell lymphomas. We have modeled acute EBV infection of naive and GC B cells in mice through timed expression of LMP1 and LMP2A. Although lethal when induced in all B cells, induction of LMP1 and LMP2A in just a small fraction of naive B cells initiated a phase of rapid B-cell expansion followed by a proliferative T-cell response, clearing the LMP-expressing B cells. Interfering with T-cell activity prevented clearance of LMP-expressing B cells. This was also true for perforin deficiency, which in the human causes a life-threatening EBV-related immunoproliferative syndrome. LMP expression in GC B cells impeded the GC reaction but, upon loss of T-cell surveillance, led to fatal B-cell expansion. Thus, timed expression of LMP1 together with LMP2A in subsets of mouse B cells allows one to study major clinically relevant features of human EBV infection in vivo, opening the way to new therapeutic approaches.

  9. [Secondary orbital lymphoma].

    Science.gov (United States)

    Basanta, I; Sevillano, C; Álvarez, M D

    2015-09-01

    A case is presented of an 85 year-old Caucasian female with lymphoma that recurred in the orbit (secondary ocular adnexal lymphoma). The orbital tumour was a diffuse large B-cell lymphoma according to the REAL classification (Revised European-American Lymphoma Classification). Orbital lymphomas are predominantly B-cell proliferations of a variety of histological types, and most are low-grade tumours. Patients are usually middle-aged or elderly, and it is slightly more common in women. A palpable mass, proptosis and blepharoptosis are the most common signs of presentation. Copyright © 2011 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  10. Lymphoma Research Foundation

    Science.gov (United States)

    ... Follow LRF Watch LRF Contact Us National Headquarters Wall Street Plaza 88 Pine Street, Suite 2400 | New York, NY 10005 212-349-2910 | 212-349-2886 Fax LRF@lymphoma.org LRF Helpline 800-500-9976 Helpline@lymphoma.org © 2012 Lymphoma Research Foundation | Privacy Policy

  11. Molecular diagnosis of Burkitt's lymphoma

    NARCIS (Netherlands)

    Dave, SS; Fu, K; Wright, GW; Lam, LT; Kluin, P; Boerma, EJ; Greiner, TC; Weisenburger, DD; Rosenwald, A; Ott, G; Muller-Hermelink, H; Gascoyne, RD; Delabie, J; Rimsza, LM; Braziel, RM; Grogan, TM; Campo, E; Jaffe, ES; Dave, BJ; Sanger, W; Bast, M; Vose, JM; Armitage, JO; Connors, JM; Smeland, EB; Kvaloy, S; Holte, H; Fisher, RI; Miller, TP; Montserrat, E; Wilson, WH; Bahl, M; Zhao, H; Yang, LM; Powell, J; Simon, R; Chan, WC; Staudt, LM

    2006-01-01

    Background: The distinction between Burkitt's lymphoma and diffuse large-B-cell lymphoma is crucial because these two types of lymphoma require different treatments. We examined whether gene-expression profiling could reliably distinguish Burkitt's lymphoma from diffuse large-B-cell lymphoma.

  12. Transformation of follicular lymphoma to plasmablastic lymphoma with c-myc gene rearrangement.

    Science.gov (United States)

    Ouansafi, Ihsane; He, Bing; Fraser, Cory; Nie, Kui; Mathew, Susan; Bhanji, Rumina; Hoda, Rana; Arabadjief, Melissa; Knowles, Daniel; Cerutti, Andrea; Orazi, Attilio; Tam, Wayne

    2010-12-01

    Follicular lymphoma (FL) is an indolent lymphoma that transforms to high-grade lymphoma, mostly diffuse large B-cell lymphoma, in about a third of patients. We present the first report of a case of FL that transformed to plasmablastic lymphoma (PBL). Clonal transformation of the FL to PBL was evidenced by identical IGH/BCL2 gene rearrangements and VDJ gene usage in rearranged IGH genes. IGH/ BCL2 translocation was retained in the PBL, which also acquired c-myc gene rearrangement. Genealogic analysis based on somatic hypermutation of the rearranged IGH genes of both FL and PBL suggests that transformation of the FL to PBL occurred most likely by divergent evolution from a common progenitor cell rather than direct evolution from the FL clone. Our study of this unusual case expands the histologic spectrum of FL transformation and increases our understanding of the pathogenetic mechanisms of transformation of indolent lymphomas to aggressive lymphomas.

  13. Therapy of non-Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    Coffey, J.; Hodgson, D.C.; Gospodarowicz, M.K.

    2003-01-01

    Non-Hodgkin's lymphomas are a heterogeneous group of malignancies of the lymphoid system. The exact etiology for most lymphomas has not been determined, but both viral and bacterial infections have been shown to be important etiologic factors. The WHO classification of hematopoietic and lymphoid tumours classifies lymphomas into B-cell and T-cell neoplasms. B-cell lymphomas account for more than 85% of all lymphomas. The Ann Arbor staging classification has been adopted by the AJCC and UICC as a standard for classifying extent of anatomic disease. The two most common histologic disease entities are follicular lymphomas and diffuse large B-cell lymphomas. The management of follicular lymphomas is used as a paradigm for the management of all indolent lymphomas. Radiation therapy is used for stage I and II disease, while alkylating agent chemotherapy, immunotherapy and radioimmunotherapy are most frequently used in stage III and IV disease that requires treatment. Most patients with follicular lymphoma enjoy prolonged survival, but at present there is no evidence that those with stage III and IV follicular lymphoma can be cured. Diffuse large B-cell lymphomas serve as a paradigm for treating aggressive lymphomas. Stage I and II diffuse large cell lymphomas are generally treated with combined modality therapy with doxorubicin-based chemotherapy followed by involved field radiation therapy, while those with stage III and IV disease are treated with chemotherapy alone. Patients who fail initial management are treated with further chemotherapy. High-dose chemotherapy with stem cell rescue has been shown to be particularly effective as salvage treatment for diffuse large cell lymphomas. The management of a heterogeneous group of primary extranodal lymphomas in general follows the above treatment principles, with additional treatment being required for those with a high risk of CNS failures, or involvement of contralateral paired organs. The management of MALT lymphomas

  14. Mouse Model of Burn Wound and Infection

    DEFF Research Database (Denmark)

    Calum, Henrik; Høiby, Niels; Moser, Claus

    2017-01-01

    The immunosuppression induced by thermal injury renders the burned victim susceptible to infection. A mouse model was developed to examine the immunosuppression, which was possible to induce even at a minor thermal insult of 6% total body surface area. After induction of the burn (48 hr) a depres......The immunosuppression induced by thermal injury renders the burned victim susceptible to infection. A mouse model was developed to examine the immunosuppression, which was possible to induce even at a minor thermal insult of 6% total body surface area. After induction of the burn (48 hr...

  15. Asparagine and glycine metabolism in rat liver mitochondria and in mouse L5178Y lymphoma cells resistant or sensitive to the anticancer drug L-asparaginase

    Energy Technology Data Exchange (ETDEWEB)

    Keefer, J.F. Jr.

    1986-01-01

    Rat liver mitochondrial asparagine was found to be degraded via an aminotransferase and omega-amidase. Evidence includes oxaloacetate production from asparagine only when glyoxylate was added and production of radiolabeled ..cap alpha..-ketosuccinamate via metabolism of (U-/sup 14/C)asparagine. In the cytosol, asparagine is degraded primarily via asparaginase and subsequent transamination. A new HPLC technique for separation of citric acid cycle intermediates was developed using: ion pairing with 20 mM each to tetrabutylammonium hydroxide and Na/sub 2/SO/sub 4/; pH 7.0; isocratic elution; and detection at 210 nm. Amino acid content of mouse lymphoma cells either sensitive (L5178Y) or resistant (L5178Y/L-ASE) to the anticancer drug L-asparaginase was studied. The concentration of asparagine was 1.5 times higher and the concentrations of the essential amino acids histidine, methionine, valine and phenylalanine were two times higher in asparaginase-resistant than sensitive cells. In vivo but not in vitro studies indicated that glucine decreases in sensitive but not resistant cells upon asparaginase treatment. Asparagine and glycine metabolism was further studied using /sup 14/C radiolabel conversion of asparagine, glyoxylate, glycine and serine. Glycine metabolism is especially important in lymphomas and leukemias because these cells contain higher concentrations of glycine that other cancer and normal cells. Therefore, glycine levels were studied and were found to decrease in sensitive but not resistant cells upon asparaginase administration.

  16. Spontaneous pyrogen production by mouse histiocytic and myelomonocytic tumor cell lines in vitro.

    Science.gov (United States)

    Bodel, P

    1978-05-01

    Tumor-associated fever occurs commonly in acute leukemias and lymphomas. We investigated the capacity for in vitro production of pyrogen by three mouse histiocytic lymphoma cell lines (J-774, PU5-1.8, p 388 D1), one myelomonoyctic line (WEHI-3), and tow lymphoma-derived lines, RAW-8 and R-8. Pyrogen was released spontaneously into the culture medium during growth by all cell lines with macrophage or myeloid characteristics including lysozyme production; R-8 cells, of presumed B-lymphocyte origin, did not produce pyrogen. When injected into mice, the pyrogens gave fever curves typical of endogenous pyrogen, were inactived by heating to 56 degrees C and by pronase digestion, and appeared to be secreted continuously by viable cells. Two pyrogenic molecular species produced by H-774 cells were identified by Sephadex filtration, one of mol wt approximately equal to 30,000, and the other greater than or equal to 60,000. By contrast, three carcinoma cell lines of human origin and SV-40 3T3 mouse fibroblasts did not produce pyrogen in vitro. These results suggest that some malignant cells derived from phagocytic cells of bone marrow origin retain their capacity for pyrogen production, and may spontaneously secrete pyrogen during growth.

  17. Imaging of MALT lymphomas

    International Nuclear Information System (INIS)

    Rodallec, M.; Guermazi, A.; Attal, P.; Zagdanski, A.M.; Frija, J.; De Kerviler, E.; Brice, P.

    2002-01-01

    The broad category of non-Hodgkin's lymphoma includes a large variety of different diseases including indolent as well as aggressive lymphomas. Mucosa-associated lymphoid tissue (MALT) lymphoma arises in the extranodal mucosal lymphoid tissue and has only been recognised as a distinct entity in recent years. It affects one or several extranodal structures such as the stomach, the lung, the eye and salivary glands. The lymphoma is generally of low grade and has indolent course. The aim of this article is to exemplify the most common radiological patterns of MALT lymphoma. (orig.)

  18. A Mouse Model of Chronic West Nile Virus Disease.

    Directory of Open Access Journals (Sweden)

    Jessica B Graham

    2016-11-01

    Full Text Available Infection with West Nile virus (WNV leads to a range of disease outcomes, including chronic infection, though lack of a robust mouse model of chronic WNV infection has precluded identification of the immune events contributing to persistent infection. Using the Collaborative Cross, a population of recombinant inbred mouse strains with high levels of standing genetic variation, we have identified a mouse model of persistent WNV disease, with persistence of viral loads within the brain. Compared to lines exhibiting no disease or marked disease, the F1 cross CC(032x013F1 displays a strong immunoregulatory signature upon infection that correlates with restraint of the WNV-directed cytolytic response. We hypothesize that this regulatory T cell response sufficiently restrains the immune response such that a chronic infection can be maintained in the CNS. Use of this new mouse model of chronic neuroinvasive virus will be critical in developing improved strategies to prevent prolonged disease in humans.

  19. Esophageal Cancer: Insights from Mouse Models

    Directory of Open Access Journals (Sweden)

    Marie-Pier Tétreault

    2015-01-01

    Full Text Available Esophageal cancer is the eighth leading cause of cancer and the sixth most common cause of cancer-related death worldwide. Despite recent advances in the development of surgical techniques in combination with the use of radiotherapy and chemotherapy, the prognosis for esophageal cancer remains poor. The cellular and molecular mechanisms that drive the pathogenesis of esophageal cancer are still poorly understood. Hence, understanding these mechanisms is crucial to improving outcomes for patients with esophageal cancer. Mouse models constitute valuable tools for modeling human cancers and for the preclinical testing of therapeutic strategies in a manner not possible in human subjects. Mice are excellent models for studying human cancers because they are similar to humans at the physiological and molecular levels and because they have a shorter gestation time and life cycle. Moreover, a wide range of well-developed technologies for introducing genetic modifications into mice are currently available. In this review, we describe how different mouse models are used to study esophageal cancer.

  20. Establishment of imageable model of T-cell lymphoma growing in syngenic mice

    Czech Academy of Sciences Publication Activity Database

    Větvička, David; Hovorka, Ondřej; Kovář, Lubomír; Říhová, Blanka

    2009-01-01

    Roč. 29, č. 11 (2009), s. 4513-4518 ISSN 0250-7005 R&D Projects: GA AV ČR IAA400200702; GA AV ČR KAN200200651; GA ČR GD310/08/H077 Institutional research plan: CEZ:AV0Z50200510 Keywords : Imageable model * EL-4 T- cell lymphoma * whole body imaging Subject RIV: EC - Immunology Impact factor: 1.428, year: 2009

  1. Immunohistochemical Characterization of Canine Lymphomas

    Directory of Open Access Journals (Sweden)

    Roxana CORA

    2017-11-01

    Full Text Available Lymphomas occur by clonal expansion of lymphoid cells and have distinctive morphological and immunophenotypic features. Determination of canine lymphoma immunophenotype is useful for accurate prognosis and further therapy. In the suggested study, we performed an immunohistochemical evaluation of some cases with canine lymphoma diagnosed in the Department of Pathology (Faculty of Veterinary Medicine, Cluj-Napoca, Romania, in order to characterize them. The investigation included 39 dogs diagnosed with different anatomical forms of lymphoma, following necropsy analysis or assessment of biopsies. The diagnosis of lymphoma was confirmed by necropsy and histopathology (Hematoxylin-eosin stain examinations. The collected specimens were analyzed by immunohistochemistry technique (automatic method using the following antibodies: CD3, CD20, CD21 and CD79a. The analyzed neoplasms were characterized as follows: about 64.10% of cases were diagnosed as B-cell lymphomas, 33.34% of cases as T-cell lymphomas, whereas 2.56% of cases were null cell type lymphomas (neither B nor T. Most of multicentric (80%, mediastinal (60% and primary central nervous system lymphomas (100% had B immunophenotype, while the majority of cutaneous (80% and digestive (100% lymphomas had T immunophenotype. Immunohistochemical description of canine lymphomas can deliver some major details concerning their behavior and malignancy. Additionally, vital prognosis and efficacy of some therapeutic protocols are relying on the immunohistochemical features of canine lymphoma.

  2. Using the mouse to model human disease: increasing validity and reproducibility

    Directory of Open Access Journals (Sweden)

    Monica J. Justice

    2016-02-01

    Full Text Available Experiments that use the mouse as a model for disease have recently come under scrutiny because of the repeated failure of data, particularly derived from preclinical studies, to be replicated or translated to humans. The usefulness of mouse models has been questioned because of irreproducibility and poor recapitulation of human conditions. Newer studies, however, point to bias in reporting results and improper data analysis as key factors that limit reproducibility and validity of preclinical mouse research. Inaccurate and incomplete descriptions of experimental conditions also contribute. Here, we provide guidance on best practice in mouse experimentation, focusing on appropriate selection and validation of the model, sources of variation and their influence on phenotypic outcomes, minimum requirements for control sets, and the importance of rigorous statistics. Our goal is to raise the standards in mouse disease modeling to enhance reproducibility, reliability and clinical translation of findings.

  3. The Danish National Lymphoma Registry

    DEFF Research Database (Denmark)

    Arboe, Bente; El-Galaly, Tarec Christoffer; Clausen, Michael Roost

    2016-01-01

    BACKGROUND: The Danish National Lymphoma Register (LYFO) prospectively includes information on all lymphoma patients newly diagnosed at hematology departments in Denmark. The validity of the clinical information in the LYFO has never been systematically assessed. AIM: To test the coverage and data...... of 3% (N = 364) was made from all patients in the LYFO. In addition, four subtypes of lymphomas were validated: CNS lymphomas, diffuse large B-cell lymphomas, peripheral T-cell lymphomas, and Hodgkin lymphomas. A total of 1,706 patients from the period 2000-2012 were included. The positive predictive...... was good with high PPVs (87% to 100%), and high completeness (92% to 100%). CONCLUSION: The LYFO is a unique, nationwide clinical database characterized by high validity, good coverage and prospective data entry. It represents a valuable resource for future lymphoma research....

  4. Hodgkin lymphoma

    Science.gov (United States)

    Lymphoma - Hodgkin; Hodgkin disease; Cancer - Hodgkin lymphoma ... to 70 years old. Past infection with the Epstein-Barr virus ( EBV ) is thought to contribute to some cases. People with HIV infection are at increased risk compared to the general population.

  5. Rituximab Treatment Prevents Lymphoma Onset in Gastric Cancer Patient-Derived Xenografts

    Directory of Open Access Journals (Sweden)

    Simona Corso

    2018-05-01

    Full Text Available Patient-Derived Xenografts (PDXs, entailing implantation of cancer specimens in immunocompromised mice, are emerging as a valuable translational model that could help validate biologically relevant targets and assist the clinical development of novel therapeutic strategies for gastric cancer.More than 30% of PDXs generated from gastric carcinoma samples developed human B-cell lymphomas instead of gastric cancer. These lymphomas were monoclonal, Epstein Barr Virus (EBV positive, originated tumorigenic cell cultures and displayed a mutational burden and an expression profile distinct from gastric adenocarcinomas. The ability of grafted samples to develop lymphomas did not correlate with patient outcome, nor with the histotype, the lymphocyte infiltration level, or the EBV status of the original gastric tumor, impeding from foreseeing lymphoma onset. Interestingly, lymphoma development was significantly more frequent when primary rather than metastatic samples were grafted.Notably, the development of such lympho-proliferative disease could be prevented by a short rituximab treatment upon mice implant, without negatively affecting gastric carcinoma engraftment.Due to the high frequency of human lymphoma onset, our data show that a careful histologic analysis is mandatory when generating gastric cancer PDXs. Such care would avoid misleading results that could occur if testing of putative gastric cancer therapies is performed in lymphoma PDXs. We propose rituximab treatment of mice to prevent lymphoma development in PDX models, averting the loss of human-derived samples.

  6. Discordant lymphoma consisting of splenic mantle cell lymphoma and marginal zone lymphoma involving the bone marrow and peripheral blood: a case report

    Directory of Open Access Journals (Sweden)

    Caracciolo Francesco

    2011-09-01

    Full Text Available Abstract Introduction Discordant lymphomas are rare entities characterized by the simultaneous presence of two distinct types of lymphomas in different anatomic sites. We describe a very rare case of simultaneous occurrence of splenic mantle cell lymphoma and marginal zone lymphoma involving the bone marrow and peripheral blood. Case presentation We report the case of a 60-year-old asymptomatic Caucasian woman in whom discordant lymphomas were discovered when a slight lymphocytosis and a conspicuous splenomegaly were observed. The different morphological, immunophenotypical and immunohistochemical features found in the different pathologic samples obtained from peripheral blood, bone marrow and spleen sections made it possible to differentiate two types of non-Hodgkin B-cell lymphomas: a mantle cell lymphoma infiltrating the spleen and a marginal zone lymphoma involving both the bone marrow and peripheral blood. Since a similar IgH gene rearrangement was found both in the bone marrow and in the spleen, the hypothesis of a common origin, followed by a different clonal selection of the neoplastic lymphocytes may be taken into consideration. Conclusion Our case emphasizes the usefulness of investigating simultaneous specimens from different anatomic sites from the same patient and the relevant diagnostic role of splenectomy.

  7. The Aβ6w302 gene and molecular mechanisms of resistance to the spread of lymphoma in a mouse mutant, Survivor-27

    International Nuclear Information System (INIS)

    Liu, Y.; Savinov, A.Yu.; McMinimy, D.L.; Kremlev, S.G.; Chapoval, A.I.; Egorov, I.K.

    2000-01-01

    The Aβ6 w302 gene and molecular mechanisms of resistance to the spread of lymphoma induced by γ-radiation ( 60 Co) in a mouse mutant, survivor-27 were studied. Metastatic tumors escape from immune response and spread in the body; survivors are very rare. Novel single exon genes Aβ4-7 and a pseudogene Aβ8Ψ have been cloned from survivors. Their protein coding sequences are similar major histocompatibility complex (MHC) class II β H2-Ab cDNA while their promoter is different from MHC promoters. The Aβ4 protein was demonstrated on macrophages (antigen presenting cells). The Aβ gene family is genetically unstable in germ line and somatic cells of survivors. Mutants S-27 and S-87/1 lost the Aβ5 s5 and acquired the Aβ6 w302 gene; the Ab gene mutated in S-27. The proposed mechanism of resistance is molecular instability of the Aβ gene family resulting in somatic mutations and wandering immune responses that destroy the tumor in the survivor [ru

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

    OpenAIRE

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

    2016-01-01

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

  9. How I treat double-hit lymphoma.

    Science.gov (United States)

    Friedberg, Jonathan W

    2017-08-03

    The 2016 revision of the World Health Organization (WHO) classification for lymphoma has included a new category of lymphoma, separate from diffuse large B-cell lymphoma, termed high-grade B-cell lymphoma with translocations involving myc and bcl-2 or bcl-6 . These lymphomas, which occur in hit lymphomas (or triple-hit lymphomas if all 3 rearrangements are present). It is important to differentiate these lymphomas from the larger group of double-expressor lymphomas, which have increased expression of MYC and BCL-2 and/or BCL-6 by immunohistochemistry, by using variable cutoff percentages to define positivity. Patients with double-hit lymphomas have a poor prognosis when treated with standard chemoimmunotherapy and have increased risk of central nervous system involvement and progression. Double-hit lymphomas may arise as a consequence of the transformation of the underlying indolent lymphoma. There are no published prospective trials in double-hit lymphoma, however retrospective studies strongly suggest that aggressive induction regimens may confer a superior outcome. In this article, I review my approach to the evaluation and treatment of double-hit lymphoma, with an eye toward future clinical trials incorporating rational targeted agents into the therapeutic armamentarium. © 2017 by The American Society of Hematology.

  10. FDG-PET in lymphomas

    International Nuclear Information System (INIS)

    Knapp, W. H.

    2009-01-01

    Lymphomas are a heterogeneous group of neoplasms in which two major subtypes are distinguished, Hodgkin's disease (HD) and non-Hodgkin's lymphomas (NHL). The incidence of lymphomas is about 20 per 100000 inhabitants (Jemal et al 2002) and 7-8 times higher than that of HD. Since NHL has a worse prognosis, the death rates of NHL are 14 times higher than those for HD. Lymphomas account for about 4 % of all cancer incidences. In USA, lymphomas are the fifth most frequent cancer type diagnosed and the third most frequent form of cancer death (Jemal et al 2002). Concerning HD, there is a preponderance for males with a gender ratio of 1.33 for incidence and 1.12 for mortality. For NHL incidences and mortality rates of genders are almost equal. HL comprises different subtypes among which nodular sclerosis is the most frequent one (60-70 %). Other histopathologic subtypes are those of mixed cellularity, lymphocyte reach and lymphocyte depleted characteristics. The most frequent subgroup of NHL are B-cell lymphomas (80-90 % of all NHL). Two thirds of this subgroup are diffuse large B-cell lymphomas, one third follicular lymphomas. Other (less frequent) subtypes are mantle cell, peripheral T-cell, anaplastic large-cell-lymphomas etc. For NHL increasing incidence has been observed in the last decades. Within 15 years the incidence increased by 50 % in the USA (Jemal et al 2002). Etiology of lymphomas is still unknown. In a certain proportion of NHL viral causes are assumed. Diagnosis is based on histology (needle biopsy) with consecutive sub typing. Prognosis depends on stage, expansion state, histology and proliferation rates. (author)

  11. Lymphoma induction by heterocyclic amines in Eu-pim-1 transgenic mice

    DEFF Research Database (Denmark)

    Sørensen, Ilona Kryspin; Kristiansen, E.; Mortensen, Alicja

    1997-01-01

    The usefulness of transgenic E mu-pim-1 mice bearing in their genome the pim-1 oncogene supplemented with an upstream immunoglobulin enhancer and a downstream murine leukaemia virus long terminal repeat, as sensitive test organisms was studied in two short-term carcinogenicity studies. The mice...... to bacteria and cultured mammalian cells. PhIP is a potent mouse lymphomagen, while IQ is a liver, lung and forestomach carcinogen in mice. We found that transgenic E mu-pim-1 mice are highly susceptible to PhIP induced lymphomagenesis but do not respond to IQ treatment. PhIP feeding of E mu-pim-1 mice...... not only increased the total number of T-cell lymphomas but also decreased the latency time compared to either transgenic or wild-type controls. The effect was most pronounced in the treated female E mu-pim-1 mice, which showed a higher incidence of PhIP induced T-cell lymphomas than transgenic males...

  12. A phase 2 study of weekly temsirolimus and bortezomib for relapsed or refractory B-cell non-Hodgkin lymphoma: A Wisconsin Oncology Network study.

    Science.gov (United States)

    Fenske, Timothy S; Shah, Namrata M; Kim, Kyung Mann; Saha, Sandeep; Zhang, Chong; Baim, Arielle E; Farnen, John P; Onitilo, Adedayo A; Blank, Jules H; Ahuja, Harish; Wassenaar, Tim; Qamar, Rubina; Mansky, Patrick; Traynor, Anne M; Mattison, Ryan J; Kahl, Brad S

    2015-10-01

    Proteasome inhibitors and mammalian target of rapamycin inhibitors each have activity in various B-cell malignancies and affect distinct cellular pathways. Their combination has demonstrated synergy in vitro and in mouse models. The authors conducted a single-arm, phase 2 trial of combined temsirolimus and bortezomib in patients with relapsed and refractory B-cell non-Hodgkin lymphoma (NHL) using a dosing scheme that was previously tested in multiple myeloma. The patients received bortezomib and temsirolimus weekly on days 1, 8, 15, and 22 of a 35-day cycle. Of 39 patients who received treatment, 3 achieved a complete response (7.7%; 95% confidence interval [CI], 1.6%-21%), and 9 had a partial response (PR) (23%; 95% CI, 11%-39%). Thus, the overall response rate (12 of 39 patients) was 31% (95% CI, 17%-48%), and the median progression-free survival was 4.7 months (95% CI, 2.1-7.8 months; 2 months for patients with diffuse large B-cell lymphoma [n = 18], 7.5 months for those with mantle cell lymphoma [n = 7], and 16.5 months for those with follicular lymphoma [n = 9]). Two extensively treated patients with diffuse large B-cell lymphoma achieved a complete response. There were no unexpected toxicities from the combination. The current results demonstrate that the combination of a mammalian target of rapamycin inhibitor and a proteasome inhibitor is safe and has activity in patients with heavily pretreated B-cell NHL. Further studies with this combination are warranted in specific subtypes of NHL. © 2015 American Cancer Society.

  13. Immunotherapy with rituximab in follicular lymphomas.

    Science.gov (United States)

    Saguna, Carmen; Mut, Ileana Delia; Lupu, Anca Roxana; Tevet, Mihaela; Bumbea, Horia; Dragan, Cornel

    2011-04-01

    Non-Hodgkin Lymphomas (NHL) represent a recent and fascinating domain of hemato-oncology, in which remarkable progress has been made. The conventional treatments of indolent lymphomas do not extend the survival rate, nor do they cure. Recent directions are centered on using several new drugs that are capable of overcoming the mechanisms that are resistant to recovery. The initiation of immunotherapy (Rituximab in 1997) seems to have changed the natural evolution of follicular lymphomas (FL). It is possible that resistance to healing in follicular lymphomas may be neutralized with Rituximab by suppressing STAT-1 positive macrophages that are present in the cellular microenvironment.Thereinafter, the re-evaluation of recent models of prognostic and therapeutic paradigmas that were used in FL became compulsory.The purpose of the paper is to compare the evolution of patients with follicular lymphoma and the period of response, according to the treatments. The study group consisted of the 71 patients diagnosed with follicular lymphoma, out of a total of 767 malignant lymphatic proliferations with B cells, for a period of 7 years (2002-2008), at the Hematology Department, Hospital Coltea, Bucharest and Hematology Department, Universitary Hospital, BucharestResults and conclusions: Combining chemotherapy with Rituximab had better results compared to the same chemotherapy, administered alone, both in induction and in case of relapse. The overall response rate in our study group was 74.7%, out of which 42.3% complete remissions. The overall response rate was 84.61% in the Rituximab group, compared to 68.88% in patients without Rituximab.

  14. Imaging of non-hodgkin lymphomas

    DEFF Research Database (Denmark)

    El-Galaly, Tarec Christoffer; Hutchings, Martin

    2015-01-01

    Optimal lymphoma management requires accurate pretreatment staging and reliable assessment of response, both during and after therapy. Positron emission tomography with computerized tomography (PET/CT) combines functional and anatomical imaging and provides the most sensitive and accurate methods...... for lymphoma imaging. New guidelines for lymphoma imaging and recently revised criteria for lymphoma staging and response assessment recommend PET/CT staging, treatment monitoring, and response evaluation in all FDG-avid lymphomas, while CT remains the method of choice for non-FDG-avid histologies. Since...... interim PET imaging has high prognostic value in lymphoma, a number of trials investigate PET-based, response-adapted therapy for non-Hodgkin lymphomas (NHL). PET response is the main determinant of response according to the new response criteria, but PET/CT has little or no role in routine surveillance...

  15. Multimodality imaging of cardiothoracic lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Carter, Brett W., E-mail: bcarter2@mdanderson.org [The University of Texas MD Anderson Cancer Center, Department of Diagnostic Radiology, Section of Thoracic Imaging, 1515 Holcombe Blvd., Unit 1478, Houston, TX 77030 (United States); Wu, Carol C. [Department of Radiology, Massachusetts General Hospital, 55 Fruit Street, FND-202, Boston, MA 02114 (United States); Khorashadi, Leila [Department of Radiology, Mount Auburn Hospital, Cambridge, MA 02138 (United States); Godoy, Myrna C.B.; Groot, Patricia M. de [The University of Texas MD Anderson Cancer Center, Department of Diagnostic Radiology, Section of Thoracic Imaging, 1515 Holcombe Blvd., Unit 1478, Houston, TX 77030 (United States); Abbott, Gerald F. [Department of Radiology, Massachusetts General Hospital, 55 Fruit Street, FND-202, Boston, MA 02114 (United States); Lichtenberger III, John P. [Department of Radiology, David Grant Medical Center, Travis AFB, CA 94535 (United States)

    2014-08-15

    Lymphoma is the most common hematologic malignancy and represents approximately 5.3% of all cancers. The World Health Organization published a revised classification scheme in 2008 that groups lymphomas by cell type and molecular, cytogenetic, and phenotypic characteristics. Most lymphomas affect the thorax at some stage during the course of the disease. Affected structures within the chest may include the lungs, mediastinum, pleura, and chest wall, and lymphomas may originate from these sites as primary malignancies or secondarily involve these structures after arising from other intrathoracic or extrathoracic sources. Pulmonary lymphomas are classified into one of four types: primary pulmonary lymphoma, secondary pulmonary lymphoma, acquired immunodeficiency syndrome-related lymphoma, and post-transplantation lymphoproliferative disorders. Although pulmonary lymphomas may produce a myriad of diverse findings within the lungs, specific individual features or combinations of features can be used, in combination with secondary manifestations of the disease such as involvement of the mediastinum, pleura, and chest wall, to narrow the differential diagnosis. While findings of thoracic lymphoma may be evident on chest radiography, computed tomography has traditionally been the imaging modality used to evaluate the disease and effectively demonstrates the extent of intrathoracic involvement and the presence and extent of extrathoracic spread. However, additional modalities such as magnetic resonance imaging of the thorax and {sup 18}F-FDG PET/CT have emerged in recent years and are complementary to CT in the evaluation of patients with lymphoma. Thoracic MRI is useful in assessing vascular, cardiac, and chest wall involvement, and PET/CT is more accurate in the overall staging of lymphoma than CT and can be used to evaluate treatment response.

  16. Authentication of primordial characteristics of the CLBL-1 cell line prove the integrity of a canine B-cell lymphoma in a murine in vivo model.

    Science.gov (United States)

    Rütgen, Barbara C; Willenbrock, Saskia; Reimann-Berg, Nicola; Walter, Ingrid; Fuchs-Baumgartinger, Andrea; Wagner, Siegfried; Kovacic, Boris; Essler, Sabine E; Schwendenwein, Ilse; Nolte, Ingo; Saalmüller, Armin; Murua Escobar, Hugo

    2012-01-01

    Cell lines are key tools in cancer research allowing the generation of neoplasias in animal models resembling the initial tumours able to mimic the original neoplasias closely in vivo. Canine lymphoma is the major hematopoietic malignancy in dogs and considered as a valuable spontaneous large animal model for human Non-Hodgkin's Lymphoma (NHL). Herein we describe the establishment and characterisation of an in vivo model using the canine B-cell lymphoma cell line CLBL-1 analysing the stability of the induced tumours and the ability to resemble the original material. CLBL-1 was injected into Rag2(-/-)γ(c) (-/-) mice. The generated tumor material was analysed by immunophenotyping and histopathology and used to establish the cell line CLBL-1M. Both cell lines were karyotyped for detection of chromosomal aberrations. Additionally, CLBL-1 was stimulated with IL-2 and DSP30 as described for primary canine B-cell lymphomas and NHL to examine the stimulatory effect on cell proliferation. CLBL-1 in vivo application resulted in lymphoma-like disease and tumor formation. Immunophenotypic analysis of tumorous material showed expression of CD45(+), MHCII(+), CD11a(+) and CD79αcy(+). PARR analysis showed positivity for IgH indicating a monoclonal character. These cytogenetic, molecular, immunophenotypical and histological characterisations of the in vivo model reveal that the induced tumours and thereof generated cell line resemble closely the original material. After DSP30 and IL-2 stimulation, CLBL-1 showed to respond in the same way as primary material. The herein described CLBL-1 in vivo model provides a highly stable tool for B-cell lymphoma research in veterinary and human medicine allowing various further in vivo studies.

  17. Synergistic effect of EMF-BEMER-type pulsed weak electromagnetic field and HPMA-bound doxorubicin on mouse EL4 T-cell lymphoma.

    Science.gov (United States)

    Říhová, Blanka; Etrych, Tomáš; Šírová, Milada; Tomala, Jakub; Ulbrich, Karel; Kovář, Marek

    2011-12-01

    We have investigated the effects of low-frequency pulsed electromagnetic field (LF-EMF) produced by BEMER device on experimental mouse T-cell lymphoma EL4 growing on conventional and/or athymic (nude) mice. Exposure to EMF-BEMER slowed down the growth of tumor mass and prolonged the survival of experimental animals. The effect was more pronounced in immuno-compromised nude mice compared to conventional ones. Acceleration of tumor growth was never observed. No measurable levels of Hsp 70 or increased levels of specific anti-EL4 antibodies were detected in the serum taken from experimental mice before and at different intervals during the experiment, i.e. before solid tumor appeared, at the time of its aggressive growth, and at the terminal stage of the disease. A significant synergizing antitumor effect was seen when EL4 tumor-bearing mice were simultaneously exposed to EMF-BEMER and treated with suboptimal dose of synthetic HPMA copolymer-based doxorubicin, DOX(HYD)-HPMA. Such a combination may be especially useful for heavily treated patients suffering from advanced tumor and requiring additional aggressive chemotherapy which, however, at that time could represent almost life-threatening way of medication.

  18. President's categorical course on lymphoma

    International Nuclear Information System (INIS)

    Hoppe, Richard T.

    1997-01-01

    Improvements in the classification, staging, and treatment of the lymphomas, complemented by an improved understanding of the biology of these diseases, has led to an improved outcome of therapy for both Hodgkin's disease and many of the non-Hodgkin's lymphomas. The rapid changes that have occurred in this field in the last decade make it timely to review this subject for radiation oncologists in a comprehensive fashion. This course is designed to meet broad educational needs required for understanding these diseases and providing effective care for patients with lymphoma. The faculty includes many leaders from both laboratory and clinical disciplines dealing with lymphomas, who will address a variety of scientific and clinical topics. The morning session will be devoted to Hodgkin's disease, including new concepts in its biology, a review of clinical trials for early stage disease, a discussion of the role of high dose therapy, and description of long term complications of treatment. The afternoon sessions will be devoted to the non-Hodgkin's lymphomas, including new concepts in pathology and biology, a description of specific entities including the low grade lymphomas, MALT lymphomas, extranodal lymphomas, intermediate grade lymphomas, mantle cell lymphomas, and summary discussions of the role of radioimmuno-therapy and high dose therapy. Although the role of radiation therapy in the management of patients with lymphoma has changed dramatically in the past two decades, radiation remains the most effective single agent for the treatment of these diseases and it is especially important for radiation onologists to keep abreast of these new concepts. This course has been designed to achieve that goal

  19. CARDIAC LYMPHOMA IN DOG

    Directory of Open Access Journals (Sweden)

    G. D. Cruz

    2016-11-01

    Full Text Available Lymphoma is a lymphoid tumor that originates in hematopoietic organs such as lymph node, spleen or liver. In dogs, the overall prevalence of cardiac tumors was estimated to be only 0.19% based on the results of the survey of a large database, and lymphomas accounts for approximately 2% of all cardiac tumors. In general, the involvement of the myocardium is rarely described in canine lymphoma. Currently, there is no evidence of a viral association with primary cardiac lymphoma in dogs, but other types of immunosuppression may contribute to abnormal events, such as involvement primary cardiac. The aim of this study was to analyze a case of sudden death of a bitch, SRD, aged 10, who had the final diagnosis of cardiac lymphoma.

  20. Experimental photoallergic contact dermatitis: a mouse model

    International Nuclear Information System (INIS)

    Maguire, H.C. Jr.; Kaidbey, K.

    1982-01-01

    We have induced photoallergic contact dermatitis in mice to 3,3',4',5 tetrachlorosalicylanilide (TCSA), chlorpromazine and 6-methylcoumarin. These compounds are known to produce photoallergic contact dermatitis in humans. The photoallergic contact dermatitis reaction in the mouse is immunologically specific viz. mice photosensitized to TCSA react, by photochallenge, to that compound and not to chlorpromazine, and conversely. The reaction requires UVA at both sensitization and challenge. It appears to be T-cell mediated in that it can be passively transferred to syngeneic mice by lymph node cells from actively sensitized mice, the histology of the reactions resembles that of classic allergic contact dermatitis in mice, challenge reactions are seen at 24 but not at 4 hr, and photoallergic contact dermatitis can be induced in B-cell deficient mice. The availability of a mouse model for the study of photo-ACD will facilitate the identification of pertinent control mechanisms and may aid in the management of the disease. It is likely that a bioassay for photoallergens of humans can be based on this mouse model

  1. CHOP THERAPY INDUCED MITOCHONDRIAL REDOX STATE ALTERATION IN NON-HODGKIN'S LYMPHOMA XENOGRAFTS

    Directory of Open Access Journals (Sweden)

    H. N. XU

    2013-04-01

    Full Text Available We are interested in investigating whether cancer therapy may alter the mitochondrial redox state in cancer cells to inhibit their growth and survival. The redox state can be imaged by the redox scanner that collects the fluorescence signals from both the oxidized-flavoproteins (Fp and the reduced form of nicotinamide adenine dinucleotide (NADH in snap-frozen tissues and has been previously employed to study tumor aggressiveness and treatment responses. Here, with the redox scanner we investigated the effects of chemotherapy on mouse xenografts of a human diffuse large B-cell lymphoma cell line (DLCL2. The mice were treated with CHOP therapy, i.e., cyclophosphamide (C + hydroxydoxorubicin (H + Oncovin (O + prednisone (P with CHO administration on day 1 and prednisone administration on days 1–5. The Fp content of the treated group was significantly decreased (p = 0.033 on day 5, and the mitochondrial redox state of the treated group was slightly more reduced than that of the control group (p = 0.048. The decrease of the Fp heterogeneity (measured by the mean standard deviation had a border-line statistical significance (p = 0.071. The result suggests that the mitochondrial metabolism of lymphoma cells was slightly suppressed and the lymphomas became less aggressive after the CHOP therapy.

  2. Transgenic mouse models of hormonal mammary carcinogenesis: advantages and limitations.

    Science.gov (United States)

    Kirma, Nameer B; Tekmal, Rajeshwar R

    2012-09-01

    Mouse models of breast cancer, especially transgenic and knockout mice, have been established as valuable tools in shedding light on factors involved in preneoplastic changes, tumor development and malignant progression. The majority of mouse transgenic models develop estrogen receptor (ER) negative tumors. This is seen as a drawback because the majority of human breast cancers present an ER positive phenotype. On the other hand, several transgenic mouse models have been developed that produce ER positive mammary tumors. These include mice over-expressing aromatase, ERα, PELP-1 and AIB-1. In this review, we will discuss the value of these models as physiologically relevant in vivo systems to understand breast cancer as well as some of the pitfalls involving these models. In all, we argue that the use of transgenic models has improved our understanding of the molecular aspects and biology of breast cancer. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Malignant lymphoma in african lions (panthera leo).

    Science.gov (United States)

    Harrison, T M; McKnight, C A; Sikarskie, J G; Kitchell, B E; Garner, M M; Raymond, J T; Fitzgerald, S D; Valli, V E; Agnew, D; Kiupel, M

    2010-09-01

    Malignant lymphoma has become an increasingly recognized problem in African lions (Panthera leo). Eleven African lions (9 male and 2 female) with clinical signs and gross and microscopic lesions of malignant lymphoma were evaluated in this study. All animals were older adults, ranging in age from 14 to 19 years. Immunohistochemically, 10 of the 11 lions had T-cell lymphomas (CD3(+), CD79a(-)), and 1 lion was diagnosed with a B-cell lymphoma (CD3(-), CD79a(+)). The spleen appeared to be the primary site of neoplastic growth in all T-cell lymphomas, with involvement of the liver (6/11) and regional lymph nodes (5/11) also commonly observed. The B-cell lymphoma affected the peripheral lymph nodes, liver, and spleen. According to the current veterinary and human World Health Organization classification of hematopoietic neoplasms, T-cell lymphoma subtypes included peripheral T-cell lymphoma (4/11), precursor (acute) T-cell lymphoblastic lymphoma/leukemia (2/11), chronic T-cell lymphocytic lymphoma/leukemia (3/11), and T-zone lymphoma (1/11). The single B-cell lymphoma subtype was consistent with diffuse large B-cell lymphoma. Feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) testing by immunohistochemistry on sections of malignant lymphoma was negative for all 11 lions. One lion was seropositive for FeLV. In contrast to domestic and exotic cats, in which B-cell lymphomas are more common than T-cell lymphomas, African lions in this study had malignant lymphomas that were primarily of T-cell origin. Neither FeLV nor FIV, important causes of malignant lymphoma in domestic cats, seems to be significant in the pathogenesis of malignant lymphoma in African lions.

  4. The Comparative Diagnostic Features of Canine and Human Lymphoma

    Directory of Open Access Journals (Sweden)

    Davis M. Seelig

    2016-06-01

    Full Text Available The non-Hodgkin lymphomas (NHLs are a heterogeneous family of lymphoid malignancies that are among the most common neoplasms of both dogs and humans. Owing to shared molecular, signaling, incidence, and pathologic features, there is a strong framework supporting the utilization of canine lymphoma as a comparative, large animal model of human NHL. In alignment with the biologic similarities, the current approach towards the diagnosis and classification of canine lymphoma is based upon the human World Health Organization guidelines. While this approach has contributed to an increasing appreciation of the potential biological scope of canine lymphoma, it has also become apparent that the most appropriate diagnostic philosophy must be multimodal, namely by requiring knowledge of microscopic, immunophenotypic, and clinical features before establishing a final disease diagnosis. This review seeks to illustrate the comparative similarities and differences in the diagnosis of canine lymphoma through the presentation of the microscopic and immunophenotypic features of its most common forms.

  5. The Comparative Diagnostic Features of Canine and Human Lymphoma.

    Science.gov (United States)

    Seelig, Davis M; Avery, Anne C; Ehrhart, E J; Linden, Michael A

    2016-06-01

    The non-Hodgkin lymphomas (NHLs) are a heterogeneous family of lymphoid malignancies that are among the most common neoplasms of both dogs and humans. Owing to shared molecular, signaling, incidence, and pathologic features, there is a strong framework supporting the utilization of canine lymphoma as a comparative, large animal model of human NHL. In alignment with the biologic similarities, the current approach towards the diagnosis and classification of canine lymphoma is based upon the human World Health Organization guidelines. While this approach has contributed to an increasing appreciation of the potential biological scope of canine lymphoma, it has also become apparent that the most appropriate diagnostic philosophy must be multimodal, namely by requiring knowledge of microscopic, immunophenotypic, and clinical features before establishing a final disease diagnosis. This review seeks to illustrate the comparative similarities and differences in the diagnosis of canine lymphoma through the presentation of the microscopic and immunophenotypic features of its most common forms.

  6. Isolated orbital mass as the primary presentation of a triple-hit lymphoma transformed from a systemic follicular lymphoma

    Directory of Open Access Journals (Sweden)

    Xiao Yi Zhou

    2018-06-01

    Full Text Available Purpose: Triple-hit lymphoma is a highly aggressive B-cell lymphoma. We report a case of triple-hit lymphoma transformed from systemic follicular lymphoma (FL after 9-year remission and presented primarily as an isolated orbital mass without systemic symptoms or lymphadenopathy. Observations: A 58-year-old female presented with intermittent vertical binocular diplopia, left upper eyelid swelling and pain and was found to have a 2.9 cm orbital mass. Histological section revealed a CD10-positive large B-cell lymphoma, consistent with transformation of FL. Fluorescent in situ hybridization (FISH analysis demonstrated rearrangements involving C-MYC, BCL-2 and BCL-6 genes, indicating a high grade, triple-hit lymphoma. Conclusions and importance: Triple-hit lymphoma transformed from a low-grade lymphoma may initially present as an isolated orbital mass without systemic evidence of transformation. Early recognition of double or triple-hit lymphomas is important since these patients require aggressive chemotherapy. Keywords: Lymphoma, Triple-hit lymphoma, Orbital mass

  7. Authentication of primordial characteristics of the CLBL-1 cell line prove the integrity of a canine B-cell lymphoma in a murine in vivo model.

    Directory of Open Access Journals (Sweden)

    Barbara C Rütgen

    Full Text Available Cell lines are key tools in cancer research allowing the generation of neoplasias in animal models resembling the initial tumours able to mimic the original neoplasias closely in vivo. Canine lymphoma is the major hematopoietic malignancy in dogs and considered as a valuable spontaneous large animal model for human Non-Hodgkin's Lymphoma (NHL. Herein we describe the establishment and characterisation of an in vivo model using the canine B-cell lymphoma cell line CLBL-1 analysing the stability of the induced tumours and the ability to resemble the original material. CLBL-1 was injected into Rag2(-/-γ(c (-/- mice. The generated tumor material was analysed by immunophenotyping and histopathology and used to establish the cell line CLBL-1M. Both cell lines were karyotyped for detection of chromosomal aberrations. Additionally, CLBL-1 was stimulated with IL-2 and DSP30 as described for primary canine B-cell lymphomas and NHL to examine the stimulatory effect on cell proliferation. CLBL-1 in vivo application resulted in lymphoma-like disease and tumor formation. Immunophenotypic analysis of tumorous material showed expression of CD45(+, MHCII(+, CD11a(+ and CD79αcy(+. PARR analysis showed positivity for IgH indicating a monoclonal character. These cytogenetic, molecular, immunophenotypical and histological characterisations of the in vivo model reveal that the induced tumours and thereof generated cell line resemble closely the original material. After DSP30 and IL-2 stimulation, CLBL-1 showed to respond in the same way as primary material. The herein described CLBL-1 in vivo model provides a highly stable tool for B-cell lymphoma research in veterinary and human medicine allowing various further in vivo studies.

  8. Extra-nodal lymphoma. A survey of Japan lymphoma radiation therapy group

    International Nuclear Information System (INIS)

    Oguchi, Masahiko; Ikeda, Hiroshi; Nakamura, Shigeo

    2002-01-01

    The purpose of this study was to examine, retrospectively, national-wide clinical data of patients with localized extranodal non-Hodgkin's lymphoma (NHL) who were treated by radiation therapy with or without chemotherapy. The survey was carried out at 25 radiation oncology institutions in Japan in 1998. In 1999, according to the Revised European American Lymphoma (REAL) classification, central pathological review conducted at Aichi cancer center was carried out for the data from 7 radiation oncology institutions. The 5-year progression free survival rates (PFS) were calculated to identify prognostic factors. Survey: Data from 1, 141 patients with stage I and II NHL were recruited from 1988 through 1992. Of them, 787 patients, who were treated using definitive radiotherapy with or without chemotherapy for intermediate and high-grade lymphomas in Working Formulation, constituted the core of this study. Primary tumors arose mainly from extra-nodal organs (71%) in the head and neck (Waldeyer's ring: 41%, thyroid gland: 7%, nasal cavities: 5%, oral cavities: 4%, sinus: 3%, orbital structures: 3%, skin: 2% and etc.). The median age of 60 years for patients with extra-nodal NHL was higher than that of 56 years for patients with nodal NHL (p<0.01). Female were dominant in incidence of extra-nodal NHL arising from the thyroid gland, skin and gastrointestinal tract. The percentage of stage I to the extra-nodal NHL from orbit, sino-nasal presentation was higher than that of other NHLs. The percentage of stage II to the extra-nodal NHL from Waldeyer's ring and thyroid gland was higher than that of other NHLs. Central pathological review was carried out for pathological data from 79 patients (Waldeyer's ring: 45, thyroid gland: 19, sinonasal cavities: 15). Of these, diffuse large B cell lymphoma (DLBCL) composed 63% of all patients, mucosa associated lyumphoid tissue lymphoma (MALT-L): 16%, Natural Killer/T cell lymphoma (NK/T-L): 11%, and mantle cell lymphoma: 5% in REAL

  9. Modeling growth and dissemination of lymphoma in a co-evolving lymph node: a diffuse-domain approach

    Science.gov (United States)

    Chuang, Yao-Li; Cristini, Vittorio; Chen, Ying; Li, Xiangrong; Frieboes, Hermann; Lowengrub, John

    2013-03-01

    While partial differential equation models of tumor growth have successfully described various spatiotemporal phenomena observed for in-vitro tumor spheroid experiments, one challenge towards taking these models to further study in-vivo tumors is that instead of relatively static tissue culture with regular boundary conditions, in-vivo tumors are often confined in organ tissues that co-evolve with the tumor growth. Here we adopt a recently developed diffuse-domain method to account for the co-evolving domain boundaries, adapting our previous in-vitro tumor model for the development of lymphoma encapsulated in a lymph node, which may swell or shrink due to proliferation and dissemination of lymphoma cells and treatment by chemotherapy. We use the model to study the induced spatial heterogeneity, which may arise as an emerging phenomenon in experimental observations and model analysis. Spatial heterogeneity is believed to lead to tumor infiltration patterns and reduce the efficacy of chemotherapy, leaving residuals that cause cancer relapse after the treatment. Understanding the spatiotemporal evolution of in-vivo tumors can be an essential step towards more effective strategies of curing cancer. Supported by NIH-PSOC grant 1U54CA143907-01.

  10. NKT cell adjuvant-based tumor vaccine for treatment of myc oncogene-driven mouse B-cell lymphoma

    NARCIS (Netherlands)

    Mattarollo, Stephen R.; West, Alison C.; Steegh, Kim; Duret, Helene; Paget, Christophe; Martin, Ben; Matthews, Geoffrey M.; Shortt, Jake; Chesi, Marta; Bergsagel, P. Leif; Bots, Michael; Zuber, Johannes; Lowe, Scott W.; Johnstone, Ricky W.; Smyth, Mark J.

    2012-01-01

    Immunomodulators are effective in controlling hematologic malignancy by initiating or reactivating host antitumor immunity to otherwise poorly immunogenic and immune suppressive cancers. We aimed to boost antitumor immunity in B-cell lymphoma by developing a tumor cell vaccine incorporating

  11. A metabolomic comparison of mouse models of the Neuronal Ceroid Lipofuscinoses

    Energy Technology Data Exchange (ETDEWEB)

    Salek, Reza M.; Pears, Michael R. [University of Cambridge, Department of Biochemistry and Cambridge Systems Biology Centre (United Kingdom); Cooper, Jonathan D. [King' s College London, Pediatric Storage Disorders Laboratory, Department of Neuroscience, Institute of Psychiatry (United Kingdom); Mitchison, Hannah M. [Royal Free and University College Medical School, Department of Paediatrics and Child Health (United Kingdom); Pearce, David A. [Sanford School of Medicine of the University of South Dakota, Department of Pediatrics (United States); Mortishire-Smith, Russell J. [Johnson and Johnson PR and D (Belgium); Griffin, Julian L., E-mail: jlg40@mole.bio.cam.ac.uk [University of Cambridge, Department of Biochemistry and the Cambridge Systems Biology Centre (United Kingdom)

    2011-04-15

    The Neuronal Ceroid Lipofuscinoses (NCL) are a group of fatal inherited neurodegenerative diseases in humans distinguished by a common clinical pathology, characterized by the accumulation of storage body material in cells and gross brain atrophy. In this study, metabolic changes in three NCL mouse models were examined looking for pathways correlated with neurodegeneration. Two mouse models; motor neuron degeneration (mnd) mouse and a variant model of late infantile NCL, termed the neuronal ceroid lipofuscinosis (nclf) mouse were investigated experimentally. Both models exhibit a characteristic accumulation of autofluorescent lipopigment in neuronal and non neuronal cells. The NMR profiles derived from extracts of the cortex and cerebellum from mnd and nclf mice were distinguished according to disease/wildtype status. In particular, a perturbation in glutamine and glutamate metabolism, and a decrease in {gamma}-amino butyric acid (GABA) in the cerebellum and cortices of mnd (adolescent mice) and nclf mice relative to wildtype at all ages were detected. Our results were compared to the Cln3 mouse model of NCL. The metabolism of mnd mice resembled older (6 month) Cln3 mice, where the disease is relatively advanced, while the metabolism of nclf mice was more akin to younger (1-2 months) Cln3 mice, where the disease is in its early stages of progression. Overall, our results allowed the identification of metabolic traits common to all NCL subtypes for the three animal models.

  12. A metabolomic comparison of mouse models of the Neuronal Ceroid Lipofuscinoses

    International Nuclear Information System (INIS)

    Salek, Reza M.; Pears, Michael R.; Cooper, Jonathan D.; Mitchison, Hannah M.; Pearce, David A.; Mortishire-Smith, Russell J.; Griffin, Julian L.

    2011-01-01

    The Neuronal Ceroid Lipofuscinoses (NCL) are a group of fatal inherited neurodegenerative diseases in humans distinguished by a common clinical pathology, characterized by the accumulation of storage body material in cells and gross brain atrophy. In this study, metabolic changes in three NCL mouse models were examined looking for pathways correlated with neurodegeneration. Two mouse models; motor neuron degeneration (mnd) mouse and a variant model of late infantile NCL, termed the neuronal ceroid lipofuscinosis (nclf) mouse were investigated experimentally. Both models exhibit a characteristic accumulation of autofluorescent lipopigment in neuronal and non neuronal cells. The NMR profiles derived from extracts of the cortex and cerebellum from mnd and nclf mice were distinguished according to disease/wildtype status. In particular, a perturbation in glutamine and glutamate metabolism, and a decrease in γ-amino butyric acid (GABA) in the cerebellum and cortices of mnd (adolescent mice) and nclf mice relative to wildtype at all ages were detected. Our results were compared to the Cln3 mouse model of NCL. The metabolism of mnd mice resembled older (6 month) Cln3 mice, where the disease is relatively advanced, while the metabolism of nclf mice was more akin to younger (1-2 months) Cln3 mice, where the disease is in its early stages of progression. Overall, our results allowed the identification of metabolic traits common to all NCL subtypes for the three animal models.

  13. The cellular cancer resistance of the SR/CR mouse

    DEFF Research Database (Denmark)

    Koch, Janne; Hau, Jann; Jensen, Henrik Elvang

    2012-01-01

    The SR/CR mouse phenotype, first described in 1999 in BALB/c and later bred into C57BL/6 mice, is resistant to cancer formation following high doses of cancer cells administered intraperitoneally. The tumor cell targeting and destruction mechanisms have not been identified. By fluorescence-activa...... controls. Importantly, this differentially regulated immune response of SR/CR mice could not be found in response to challenge with the lymphoma cell line EL-4....

  14. Synergistic Anti-Tumor Activity of EZH2 Inhibitors and Glucocorticoid Receptor Agonists in Models of Germinal Center Non-Hodgkin Lymphomas.

    Science.gov (United States)

    Knutson, Sarah K; Warholic, Natalie M; Johnston, L Danielle; Klaus, Christine R; Wigle, Tim J; Iwanowicz, Dorothy; Littlefield, Bruce A; Porter-Scott, Margaret; Smith, Jesse J; Moyer, Mikel P; Copeland, Robert A; Pollock, Roy M; Kuntz, Kevin W; Raimondi, Alejandra; Keilhack, Heike

    2014-01-01

    Patients with non-Hodgkin lymphoma (NHL) are treated today with a cocktail of drugs referred to as CHOP (Cyclophosphamide, Hydroxyldaunorubicin, Oncovin, and Prednisone). Subsets of patients with NHL of germinal center origin bear oncogenic mutations in the EZH2 histone methyltransferase. Clinical testing of the EZH2 inhibitor EPZ-6438 has recently begun in patients. We report here that combining EPZ-6438 with CHOP in preclinical cell culture and mouse models results in dramatic synergy for cell killing in EZH2 mutant germinal center NHL cells. Surprisingly, we observe that much of this synergy is due to Prednisolone - a glucocorticoid receptor agonist (GRag) component of CHOP. Dramatic synergy was observed when EPZ-6438 is combined with Prednisolone alone, and a similar effect was observed with Dexamethasone, another GRag. Remarkably, the anti-proliferative effect of the EPZ-6438+GRag combination extends beyond EZH2 mutant-bearing cells to more generally impact germinal center NHL. These preclinical data reveal an unanticipated biological intersection between GR-mediated gene regulation and EZH2-mediated chromatin remodeling. The data also suggest the possibility of a significant and practical benefit of combining EZH2 inhibitors and GRag that warrants further investigation in a clinical setting.

  15. Nodular breast lymphoma

    International Nuclear Information System (INIS)

    Rodriguez, M.; Sahagun, E.; Pena, J.; Mendez, J.

    1996-01-01

    We attempt to correlate the histological types [in three cases of B-cell non-Hodgkin's lymphoma (NHL), one case of T-cell NHL and one of Hodgkin's disease] with the radiological presentation and compare our findings with the literature reviewed. Among the mammographic studies, performed over and 18-month period, we have assessed five patients (four women and one man, aged as having lymphoma. the man presented bilateral involvement. Both mammography and a broader study with ultrasound and chest and abdominal CT scan were performed in every case. Four patients underwent breast ultrasound. The definitive diagnosis was based on biopsy in all cases. Three of the five cases involved primary lymphomas and the other two were secondary. Four patients presented NHL and the remaining patient had Hodgkin's disease. In mammography, the nodules showed different degrees of margin definition. In ultrasound, all the lesion were hypoechoic. The radiological diagnosis of breast lymphoma is difficult in the absence of a previous diagnosis of lymphoma. This lesion should be included in the differential diagnosis in the presence of a breast nodule associated with axillary lymph nodes, especially when the latter are bilateral. (Author)

  16. ESMO Consensus Conference on malignant lymphoma

    DEFF Research Database (Denmark)

    Buske, C; Hutchings, M; Ladetto, M

    2018-01-01

    The European Society for Medical Oncology (ESMO) consensus conference on mature B cell lymphomas and chronic lymphocytic leukaemia (CLL) was held on 20 June 2015 in Lugano, Switzerland, and included a multidisciplinary panel of 25 leading experts. The aim of the conference was to develop recommen......The European Society for Medical Oncology (ESMO) consensus conference on mature B cell lymphomas and chronic lymphocytic leukaemia (CLL) was held on 20 June 2015 in Lugano, Switzerland, and included a multidisciplinary panel of 25 leading experts. The aim of the conference was to develop...... of the three key areas identified. This manuscript presents the consensus recommendations regarding the clinical management of elderly patients diagnosed with malignant lymphoma. Four clinically-relevant topics identified by the panel were: 1) how to define patient fitness, 2) assessing quality of life, 3......) diagnostic work-up and 4) clinical management of elderly patients with lymphoma. Each of these key topics is addressed in the context of five different lymphoma entities, namely: CLL, follicular lymphoma, mantle cell lymphoma, peripheral T-cell lymphoma and diffuse large B-cell lymphoma. Results, including...

  17. Clinicopathological study of primary gastric lymphoma

    International Nuclear Information System (INIS)

    Al-Shehabi, Zubeir A.; Saleh, Rana S.; Zezafon, Hassan B.

    2007-01-01

    Objective was to present a histopathologic and immunohistochemical analysis of primary gastric lymphomas that was reclassified according to the new World Health Organization classification of lymphoid neoplasms. We reviewed the morphological and immunohistochemical features of 28 patients with gastric lymphomas, diagnosed in the Department of pathology at the University Hospital of Tishreen University, Lattakia, Syria, during the period 1994-2003. Specimens were obtained from endoscopic and surgical biopsies. The immunohistochemical study was performed to analyze the immunophenotype of these lymphomas. Patients were aged 17-71 years. There was a slight predominance of females (male to female ratio, 13:15). Seventeen of the patients had tumors mainly located in the gastric antrum. Histologically, the most common lymphoma was of mucosa-associated lymphoid tissue (MALT) type (20 patients), also with diffuse large B-cell lymphoma (7 patients) and anaplastic large cell lymphoma (one patient). Our study demonstrates the different patterns of gastric lymphomas in Lattakia, Syria during a 10-year period in 28 Syrian patients, and reveals that the most primary gastric lymphomas are B-cell MALT lymphomas. (author)

  18. Humanized mouse models: Application to human diseases.

    Science.gov (United States)

    Ito, Ryoji; Takahashi, Takeshi; Ito, Mamoru

    2018-05-01

    Humanized mice are superior to rodents for preclinical evaluation of the efficacy and safety of drug candidates using human cells or tissues. During the past decade, humanized mouse technology has been greatly advanced by the establishment of novel platforms of genetically modified immunodeficient mice. Several human diseases can be recapitulated using humanized mice due to the improved engraftment and differentiation capacity of human cells or tissues. In this review, we discuss current advanced humanized mouse models that recapitulate human diseases including cancer, allergy, and graft-versus-host disease. © 2017 Wiley Periodicals, Inc.

  19. Differences in replicon behavior between x-irradiation-sensitive L5178Y mouse lymphoma cells and A-T fibroblasts using DNA fiber autoradiography

    International Nuclear Information System (INIS)

    Ockey, C.H.

    1983-01-01

    Replicon behavior in radiosensitive Ataxia telangiectasia (A-T) fibroblasts and mouse lymphoma L5178Y (LS) cells was studied by DNA fiber autoradiography. LS cells, irradiated at 13 Gy, showed a similar reduction in rate of DNA chain growth and initiation of replicons as did resistant (LR) cells. A progressive increase in the intensity of [ 3 H]TdR labeling of many replicons was observed after irradition in the LS cells, but not in LR cells. This indicated a reduced or absent endogenous dTTP supply after irradiation in the LS cells, implicating a defect in nucleoside precursor production. Irradiated normal human and A-T cells did not show this effect. After 2 Gy, the frequency of initiation of replicons into synthesis was temporarily reduced in the normal human but not in the A-T cells. After 20 Gy, the rate of DNA chain growth was preferentially reduced in the normal human cells, but an increase was observed in the A-T cells. This increased rate could be explained in terms of a normal supply of complexes involved in chain elongation being distributed over a reduced number of initiated replicon clusters in the A-T cells

  20. Mouse models of estrogen receptor-positive breast cancer

    Directory of Open Access Journals (Sweden)

    Shakur Mohibi

    2011-01-01

    Full Text Available Breast cancer is the most frequent malignancy and second leading cause of cancer-related deaths among women. Despite advances in genetic and biochemical analyses, the incidence of breast cancer and its associated mortality remain very high. About 60 - 70% of breast cancers are Estrogen Receptor alpha (ER-α positive and are dependent on estrogen for growth. Selective estrogen receptor modulators (SERMs have therefore provided an effective targeted therapy to treat ER-α positive breast cancer patients. Unfortunately, development of resistance to endocrine therapy is frequent and leads to cancer recurrence. Our understanding of molecular mechanisms involved in the development of ER-α positive tumors and their resistance to ER antagonists is currently limited due to lack of experimental models of ER-α positive breast cancer. In most mouse models of breast cancer, the tumors that form are typically ER-negative and independent of estrogen for their growth. However, in recent years more attention has been given to develop mouse models that develop different subtypes of breast cancers, including ER-positive tumors. In this review, we discuss the currently available mouse models that develop ER-α positive mammary tumors and their potential use to elucidate the molecular mechanisms of ER-α positive breast cancer development and endocrine resistance.

  1. Treatment results of localized gastric lymphoma

    International Nuclear Information System (INIS)

    Abe, Tatsuyuki; Gomi, Hiromichi; Sakaino, Shinjiro; Nakajima, Yasuo

    2008-01-01

    Between 2000 and 2007, 17 patients with localized gastric lymphoma (10 mucosa-associated lymphoid tissue lymphomas and 7 diffuse large B-cell lymphomas) were treated with radiotherapy alone or doxorubicin-based chemotherapy followed by radiotherapy. Radiation dose of mucosa-associated lymphoid tissue (MALT) lymphoma was 30 Gy with a daily fraction size of 1.5 Gy. Sixteen patients achieved complete remission and the 5-year overall survival of MALT lymphoma and diffuse large B-cell lymphoma (DLBCL) were 100% and 87%, respectively. No gastric perforation and hemorrhage were noticed. Using AP/LR 2-port radiotherapy markedly decreased the liver dose. (author)

  2. Intraocular lymphoma

    Directory of Open Access Journals (Sweden)

    Li-Juan Tang

    2017-08-01

    Full Text Available Intraocular lymphoma (IOL is a rare lymphocytic malignancy which contains two main distinct forms. Primary intraocular lymphoma (PIOL is mainly a sub-type of primary central nervous system lymphoma (PCNSL. Alternatively, IOL can originate from outside the central nervous system (CNS by metastasizing to the eye. These tumors are known as secondary intraocular lymphoma (SIOL. The IOL can arise in the retina, uvea, vitreous, Bruch’s membrane and optic nerve. There are predominantly of B-cell origin; however there are also rare T-cell variants. Diagnosis remains challenging for ophthalmologists and pathologists, due to its ability to masquerade as noninfectious or infectious uveitis, white dot syndromes, or occasionally as other metastatic cancers. Laboratory tests include flow cytometry, immunocytochemistry, interleukin detection (IL-10: IL-6, ratio >1, and polymerase chain reaction (PCR amplification. Methotrexate-based systemic chemotherapy with external beam radiotherapy and intravitreal chemotherapy with methotrexate are useful for controlling the disease, but the prognosis remains poor. Therefore, it is important to make an early diagnose and treatment. This review is focused on the clinical manifestations, diagnosis, treatment and prognosis of the IOL.

  3. Regulatory Forum commentary: alternative mouse models for future cancer risk assessment.

    Science.gov (United States)

    Morton, Daniel; Sistare, Frank D; Nambiar, Prashant R; Turner, Oliver C; Radi, Zaher; Bower, Nancy

    2014-07-01

    International regulatory and pharmaceutical industry scientists are discussing revision of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) S1 guidance on rodent carcinogenicity assessment of small molecule pharmaceuticals. A weight-of-evidence approach is proposed to determine the need for rodent carcinogenicity studies. For compounds with high human cancer risk, the product may be labeled appropriately without conducting rodent carcinogenicity studies. For compounds with minimal cancer risk, only a 6-month transgenic mouse study (rasH2 mouse or p53+/- mouse) or a 2-year mouse study would be needed. If rodent carcinogenicity testing may add significant value to cancer risk assessment, a 2-year rat study and either a 6-month transgenic mouse or a 2-year mouse study is appropriate. In many cases, therefore, one rodent carcinogenicity study could be sufficient. The rasH2 model predicts neoplastic findings relevant to human cancer risk assessment as well as 2-year rodent models, produces fewer irrelevant neoplastic outcomes, and often will be preferable to a 2-year rodent study. Before revising ICH S1 guidance, a prospective evaluation will be conducted to test the proposed weight-of-evidence approach. This evaluation offers an opportunity for a secondary analysis comparing the value of alternative mouse models and 2-year rodent studies in the proposed ICH S1 weight-of-evidence approach for human cancer risk assessment. © 2014 by The Author(s).

  4. Mouse models of long QT syndrome

    Science.gov (United States)

    Salama, Guy; London, Barry

    2007-01-01

    Congenital long QT syndrome is a rare inherited condition characterized by prolongation of action potential duration (APD) in cardiac myocytes, prolongation of the QT interval on the surface electrocardiogram (ECG), and an increased risk of syncope and sudden death due to ventricular tachyarrhythmias. Mutations of cardiac ion channel genes that affect repolarization cause the majority of the congenital cases. Despite detailed characterizations of the mutated ion channels at the molecular level, a complete understanding of the mechanisms by which individual mutations may lead to arrhythmias and sudden death requires study of the intact heart and its modulation by the autonomic nervous system. Here, we will review studies of molecularly engineered mice with mutations in the genes (a) known to cause long QT syndrome in humans and (b) specific to cardiac repolarization in the mouse. Our goal is to provide the reader with a comprehensive overview of mouse models with long QT syndrome and to emphasize the advantages and limitations of these models. PMID:17038432

  5. Defining the role of polyamines in colon carcinogenesis using mouse models

    Directory of Open Access Journals (Sweden)

    Natalia A Ignatenko

    2011-01-01

    Full Text Available Genetics and diet are both considered important risk determinants for colorectal cancer, a leading cause of death in the US and worldwide. Genetically engineered mouse (GEM models have made a significant contribution to the characterization of colorectal cancer risk factors. Reliable, reproducible, and clinically relevant animal models help in the identification of the molecular events associated with disease progression and in the development of effictive treatment strategies. This review is focused on the use of mouse models for studying the role of polyamines in colon carcinogenesis. We describe how the available mouse models of colon cancer such as the multiple intestinal neoplasia (Min mice and knockout genetic models facilitate understanding of the role of polyamines in colon carcinogenesis and help in the development of a rational strategy for colon cancer chemoprevention.

  6. Isolated orbital mass as the primary presentation of a triple-hit lymphoma transformed from a systemic follicular lymphoma.

    Science.gov (United States)

    Zhou, Xiao Yi; Lu, Xinyan; Raparia, Kirtee; Chen, Yi-Hua

    2018-06-01

    Triple-hit lymphoma is a highly aggressive B-cell lymphoma. We report a case of triple-hit lymphoma transformed from systemic follicular lymphoma (FL) after 9-year remission and presented primarily as an isolated orbital mass without systemic symptoms or lymphadenopathy. A 58-year-old female presented with intermittent vertical binocular diplopia, left upper eyelid swelling and pain and was found to have a 2.9 cm orbital mass. Histological section revealed a CD10-positive large B-cell lymphoma, consistent with transformation of FL. Fluorescent in situ hybridization (FISH) analysis demonstrated rearrangements involving C-MYC, BCL-2 and BCL-6 genes, indicating a high grade, triple-hit lymphoma. Triple-hit lymphoma transformed from a low-grade lymphoma may initially present as an isolated orbital mass without systemic evidence of transformation. Early recognition of double or triple-hit lymphomas is important since these patients require aggressive chemotherapy.

  7. Inhibition of Rac controls NPM–ALK-dependent lymphoma development and dissemination

    Energy Technology Data Exchange (ETDEWEB)

    Colomba, A [INSERM, U1048, Université Toulouse III, Toulouse, Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse (France); Giuriato, S; Dejean, E [Centre de Recherches en Cancérologie de Toulouse, UMR1037-Université Toulouse III, IFR150-IFRBMT, Toulouse (France); Thornber, K [INSERM, U1048, Université Toulouse III, Toulouse, Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse (France); Delsol, G [Centre de Recherches en Cancérologie de Toulouse, UMR1037-Université Toulouse III, IFR150-IFRBMT, Toulouse (France); Tronchère, H [INSERM, U1048, Université Toulouse III, Toulouse, Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse (France); Meggetto, F [Centre de Recherches en Cancérologie de Toulouse, UMR1037-Université Toulouse III, IFR150-IFRBMT, Toulouse (France); Payrastre, B; Gaits-Iacovoni, F [INSERM, U1048, Université Toulouse III, Toulouse, Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse (France)

    2011-06-01

    Nucleophosmin-anaplastic lymphoma kinase (NPM–ALK) is a tyrosine kinase oncogene responsible for the pathogenesis of the majority of human ALK-positive lymphomas. We recently reported that it activated the Rac1 GTPase in anaplastic large-cell lymphoma (ALCL), leading to Rac-dependent formation of active invadopodia required for invasiveness. Herein, we went further into the study of this pathway and used the inhibitor of Rac, NSC23766, to validate its potential as a molecular target in ALCL in vitro and in vivo in a xenograft model and in a conditional model of NPM–ALK transgenic mice. Our data demonstrate that Rac regulates important effectors of NPM–ALK-induced transformation such as Erk1/2, p38 and Akt. Moreover, inhibition of Rac signaling abrogates NPM–ALK-elicited disease progression and metastasis in mice, highlighting the potential of small GTPases and their regulators as additional therapic targets in lymphomas.

  8. Inhibition of Rac controls NPM–ALK-dependent lymphoma development and dissemination

    International Nuclear Information System (INIS)

    Colomba, A; Giuriato, S; Dejean, E; Thornber, K; Delsol, G; Tronchère, H; Meggetto, F; Payrastre, B; Gaits-Iacovoni, F

    2011-01-01

    Nucleophosmin-anaplastic lymphoma kinase (NPM–ALK) is a tyrosine kinase oncogene responsible for the pathogenesis of the majority of human ALK-positive lymphomas. We recently reported that it activated the Rac1 GTPase in anaplastic large-cell lymphoma (ALCL), leading to Rac-dependent formation of active invadopodia required for invasiveness. Herein, we went further into the study of this pathway and used the inhibitor of Rac, NSC23766, to validate its potential as a molecular target in ALCL in vitro and in vivo in a xenograft model and in a conditional model of NPM–ALK transgenic mice. Our data demonstrate that Rac regulates important effectors of NPM–ALK-induced transformation such as Erk1/2, p38 and Akt. Moreover, inhibition of Rac signaling abrogates NPM–ALK-elicited disease progression and metastasis in mice, highlighting the potential of small GTPases and their regulators as additional therapic targets in lymphomas

  9. Non-Hodgkin's lymphomas

    International Nuclear Information System (INIS)

    Glatstein, E.; Wasserman, T.H.

    1987-01-01

    Non-Hodgkin's lymphomas are a varied and complex group of diseases that must be distinguished from Hodgkin's disease. The latter almost always begins in lymph nodes and spreads primarily in an axial fashion; non-Hodgkin's lymphomas may begin either in lymph nodes or in extranodal tissue and can spread both in an axial fashion and centrifugally. Because of changes in pathology terminology and the introduction of a classification using cell surface markers, many prognostic groups of patients with lymphomas have evolved. Therapeutic choices and prognosis are greatly influenced by variations in anatomic sites and extent of disease. Currently, the decisions on management require a balancing of radiation therapy with systemic chemotherapy. In some cases, radiation therapy alone may be sufficient; however, because most patients with non-Hodgkins's lymphomas tend to have advanced disease, a large percentage of patients will be managed with chemotherapy alone or in combination with radiation therapy

  10. Psoriasis and risk of malignant lymphoma

    DEFF Research Database (Denmark)

    Kamstrup, M R; Skov, L; Zachariae, C

    2018-01-01

    In patients with psoriasis, the risk of lymphoma has been a subject of controversy and data from larger studies are limited1-4 . We therefore investigated the 5-year risk of new-onset Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL) (excluding cutaneous T-cell lymphoma [CTCL]), and CTCL...

  11. Mass spectrometry analysis of hepcidin peptides in experimental mouse models.

    Directory of Open Access Journals (Sweden)

    Harold Tjalsma

    Full Text Available The mouse is a valuable model for unravelling the role of hepcidin in iron homeostasis, however, such studies still report hepcidin mRNA levels as a surrogate marker for bioactive hepcidin in its pivotal function to block ferroportin-mediated iron transport. Here, we aimed to assess bioactive mouse Hepcidin-1 (Hep-1 and its paralogue Hepcidin-2 (Hep-2 at the peptide level. To this purpose, Fourier transform ion cyclotron resonance (FTICR and tandem-MS was used for hepcidin identification, after which a time-of-flight (TOF MS-based methodology was exploited to routinely determine Hep-1 and -2 levels in mouse serum and urine. This method was biologically validated by hepcidin assessment in: i 3 mouse strains (C57Bl/6; DBA/2 and BABL/c upon stimulation with intravenous iron and LPS, ii homozygous Hfe knock out, homozygous transferrin receptor 2 (Y245X mutated mice and double affected mice, and iii mice treated with a sublethal hepatotoxic dose of paracetamol. The results showed that detection of Hep-1 was restricted to serum, whereas Hep-2 and its presumed isoforms were predominantly present in urine. Elevations in serum Hep-1 and urine Hep-2 upon intravenous iron or LPS were only moderate and varied considerably between mouse strains. Serum Hep-1 was decreased in all three hemochromatosis models, being lowest in the double affected mice. Serum Hep-1 levels correlated with liver hepcidin-1 gene expression, while acute liver damage by paracetamol depleted Hep-1 from serum. Furthermore, serum Hep-1 appeared to be an excellent indicator of splenic iron accumulation. In conclusion, Hep-1 and Hep-2 peptide responses in experimental mouse agree with the known biology of hepcidin mRNA regulators, and their measurement can now be implemented in experimental mouse models to provide novel insights in post-transcriptional regulation, hepcidin function, and kinetics.

  12. Lymphoma of the Urinary Bladder

    Directory of Open Access Journals (Sweden)

    Anthony Kodzo-Grey Venyo

    2014-01-01

    Full Text Available Background. Lymphoma of the urinary bladder (LUB is rare. Aims. To review the literature on LUB. Methods. Various internet databases were used. Results. LUB can be either primary or secondary. The tumour has female predominance; most cases occur in middle-age women. Secondary LUB occurs in 10% to 25% of leukemias/lymphomas and in advanced-stage systemic lymphoma. Less than 100 cases have been reported. MALT typically affects adults older than 60 years; 75% are female. Diffuse large B-cell lymphoma is also common and may arise from transformation of MALT. LUB presents with haematuria, dysuria, urinary frequency, nocturia, and abdominal or back pain. Macroscopic examination of LUBs show large discrete tumours centred in the dome or lateral walls of the bladder. Positive staining of LUB varies by the subtype of lymphoma; B-cell lymphomas are CD20 positive. MALT lymphoma is positively stained for CD20, CD19, and FMC7 and negatively stained for CD5, CD10, and CD11c. LUB stains negatively with Pan-keratin, vimentin, CK20, and CK7. MALT lymphoma exhibits t(11; 18(q21: 21. Radiotherapy is an effective treatment for the MALT type of LUB with no recurrence. Conclusions. LUB is diagnosed by its characteristic morphology and immunohistochemical characteristics. Radiotherapy is a useful treatment.

  13. Mouse Models as Predictors of Human Responses: Evolutionary Medicine.

    Science.gov (United States)

    Uhl, Elizabeth W; Warner, Natalie J

    Mice offer a number of advantages and are extensively used to model human diseases and drug responses. Selective breeding and genetic manipulation of mice have made many different genotypes and phenotypes available for research. However, in many cases, mouse models have failed to be predictive. Important sources of the prediction problem have been the failure to consider the evolutionary basis for species differences, especially in drug metabolism, and disease definitions that do not reflect the complexity of gene expression underlying disease phenotypes. Incorporating evolutionary insights into mouse models allow for unique opportunities to characterize the effects of diet, different gene expression profiles, and microbiomics underlying human drug responses and disease phenotypes.

  14. Malignant lymphomas of the stomach

    International Nuclear Information System (INIS)

    Drgona, L.

    2011-01-01

    Primary gastric lymphomas are the most common extra nodal lymphomas. They can be presented as aggressive or indolent, majority of indolent lymphomas are associated to H. pylori infection. The basic diagnostic procedures are endoscopy, endo sonography and biopsy of gastric tissue. Therapy is related to the histological subtype, stage, H. pylori positivity, clinical symptoms and condition of patient. The aim of the treatment is remission as well as good quality of life. The prognosis of patients with primary gastric lymphomas is relatively good. (author)

  15. Mouse models for gastric cancer: Matching models to biological questions

    Science.gov (United States)

    Poh, Ashleigh R; O'Donoghue, Robert J J

    2016-01-01

    Abstract Gastric cancer is the third leading cause of cancer‐related mortality worldwide. This is in part due to the asymptomatic nature of the disease, which often results in late‐stage diagnosis, at which point there are limited treatment options. Even when treated successfully, gastric cancer patients have a high risk of tumor recurrence and acquired drug resistance. It is vital to gain a better understanding of the molecular mechanisms underlying gastric cancer pathogenesis to facilitate the design of new‐targeted therapies that may improve patient survival. A number of chemically and genetically engineered mouse models of gastric cancer have provided significant insight into the contribution of genetic and environmental factors to disease onset and progression. This review outlines the strengths and limitations of current mouse models of gastric cancer and their relevance to the pre‐clinical development of new therapeutics. PMID:26809278

  16. Non-Hodgkin's lymphoma - Part II: Management of primary extranodal lymphomas, generalized disease and salvage treatment

    International Nuclear Information System (INIS)

    Gospodarowicz, Mary K.; Sutcliffe, Simon B.

    1996-01-01

    Objective: To review the approach to the diagnosis, classification, assessment, treatment and continuing management of patients with primary extranodal non-Hodgkin's lymphoma, and the management of generalized disease with the emphasis on the current role of salvage treatment with high dose chemotherapy and stem cell/bone marrow support strategies. Non-Hodgkin's lymphoma may involve any part of the body. Many lymphomas, such as MALT, angiocentric T-cell, etc., commonly present in extranodal sites. Lymphomas presenting in the GI tract, and head and neck, are most common with the single most common site being the stomach. Gastric lymphoma is associated with Helicobacter pylorii and is most common in areas endemic for Helicobacter pylorii infection. Recent advances in the understanding of the etiology of gastric MALT, thyroid, and intestinal lymphomas present new opportunities for the application of novel therapeutic approaches e.g. antibiotic therapy for Helicobacter pylori and early stage IPSID. Lymphomas presenting in the orbit, thyroid, breast, bone, extradural and skin are of interest because of the importance of expert RT in securing local control. Primary brain lymphomas present a particular challenge to the radiation oncologist. Although localized, primary brain lymphomas are extremely difficult to control. Rare sites of extranodal lymphoma include testis, female genital tract, and lung. Extranodal lymphomas are often localized and cure with RT or CMT is possible. They represent a assorted group of diseases with diverse presentations, prognosis, sensitivity to RT and expected outcome. They are of particular importance to radiation oncologists as they require special attention to patterns of spread and treatment planning. The principles of management of primary extranodal lymphoma, however, follow those applicable to localized nodal presentations. Although primary extranodal lymphomas are highly curable, a proportion of patients will fail with disseminated

  17. Enzooty of non-Hodgkin's malignant lymphoma of Papio hamadryas in Sukhumi monkey colony. Clinical and morphological signs of pre-lymphoma.

    Science.gov (United States)

    Yakovleva, Lelita A; Lapin, Boris A; Agumava, Aslan A

    2018-04-01

    Inoculation of hamadryas baboons with blood of leukemia ill people-induced malignant non-Hodgkin's lymphoma in experimental animals for a very considerable latency period. At close contact of inoculated baboons with healthy non-inoculated animals, the lymphoma spread between them. The epidemiological analysis, postmortem examination, histological analysis, tissue culturing, and PCR were used for the diagnostics of lymphoma and pre-lymphoma, purification, identification of STLV-1, and HVP viruses. Characteristic clinical and morphological signs designated by us as pre-lymphoma often precede the lymphoma development. In some cases, pre-lymphoma does not develop in lymphoma because animals die from various diseases and do not reach the point of the lymphoma development. The horizontal transmission of lymphoma arising with the participation of T-lymphotropic retrovirus STLV-1 is shown. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Histologic scoring of gastritis and gastric cancer in mouse models.

    Science.gov (United States)

    Rogers, Arlin B

    2012-01-01

    Histopathology is a defining endpoint in mouse models of experimental gastritis and gastric adenocarcinoma. Presented here is an overview of the histology of gastritis and gastric cancer in mice experimentally infected with Helicobacter pylori or H. felis. A modular histopathologic scoring scheme is provided that incorporates relevant disease-associated changes. Whereas the guide uses Helicobacter infection as the prototype challenge, features may be applied to chemical and genetically engineered mouse models of stomach cancer as well. Specific criteria included in the combined gastric histologic activity index (HAI) include inflammation, epithelial defects, oxyntic atrophy, hyperplasia, pseudopyloric metaplasia, and dysplasia or neoplasia. Representative photomicrographs accompany descriptions for each lesion grade. Differentiation of genuine tumor invasion from pseudoinvasion is highlighted. A brief comparison of normal rodent versus human stomach anatomy and physiology is accompanied by an introduction to mouse-specific lesions including mucous metaplasia and eosinophilic droplets (hyalinosis). In conjunction with qualified pathology support, this guide is intended to assist research scientists, postdoctoral fellows, graduate students, and medical professionals from affiliated disciplines in the interpretation and histologic grading of chronic gastritis and gastric carcinoma in mouse models.

  19. Development of a Representative Mouse Model with Nonalcoholic Steatohepatitis.

    Science.gov (United States)

    Verbeek, Jef; Jacobs, Ans; Spincemaille, Pieter; Cassiman, David

    2016-06-01

    Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease in the Western world. It represents a disease spectrum ranging from isolated steatosis to non-alcoholic steatohepatitis (NASH). In particular, NASH can evolve to fibrosis, cirrhosis, hepatocellular carcinoma, and liver failure. The development of novel treatment strategies is hampered by the lack of representative NASH mouse models. Here, we describe a NASH mouse model, which is based on feeding non-genetically manipulated C57BL6/J mice a 'Western style' high-fat/high-sucrose diet (HF-HSD). HF-HSD leads to early obesity, insulin resistance, and hypercholesterolemia. After 12 weeks of HF-HSD, all mice exhibit the complete spectrum of features of NASH, including steatosis, hepatocyte ballooning, and lobular inflammation, together with fibrosis in the majority of mice. Hence, this model closely mimics the human disease. Implementation of this mouse model will lead to a standardized setup for the evaluation of (i) underlying mechanisms that contribute to the progression of NAFLD to NASH, and (ii) therapeutic interventions for NASH. © 2016 by John Wiley & Sons, Inc. Copyright © 2016 John Wiley & Sons, Inc.

  20. International Lymphoma Epidemiology Consortium

    Science.gov (United States)

    The InterLymph Consortium, or formally the International Consortium of Investigators Working on Non-Hodgkin's Lymphoma Epidemiologic Studies, is an open scientific forum for epidemiologic research in non-Hodgkin's lymphoma.

  1. Adoptive transfer of murine T cells expressing a chimeric-PD1-Dap10 receptor as an immunotherapy for lymphoma.

    Science.gov (United States)

    Lynch, Adam; Hawk, William; Nylen, Emily; Ober, Sean; Autin, Pierre; Barber, Amorette

    2017-11-01

    Adoptive transfer of T cells is a promising cancer therapy and expression of chimeric antigen receptors can enhance tumour recognition and T-cell effector functions. The programmed death protein 1 (PD1) receptor is a prospective target for a chimeric antigen receptor because PD1 ligands are expressed on many cancer types, including lymphoma. Therefore, we developed a murine chimeric PD1 receptor (chPD1) consisting of the PD1 extracellular domain fused to the cytoplasmic domain of CD3ζ. Additionally, chimeric antigen receptor therapies use various co-stimulatory domains to enhance efficacy. Hence, the inclusion of a Dap10 or CD28 co-stimulatory domain in the chPD1 receptor was compared to determine which domain induced optimal anti-tumour immunity in a mouse model of lymphoma. The chPD1 T cells secreted pro-inflammatory cytokines and lysed RMA lymphoma cells. Adoptive transfer of chPD1 T cells significantly reduced established tumours and led to tumour-free survival in lymphoma-bearing mice. When comparing chPD1 receptors containing a Dap10 or CD28 domain, both receptors induced secretion of pro-inflammatory cytokines; however, chPD1-CD28 T cells also secreted anti-inflammatory cytokines whereas chPD1-Dap10 T cells did not. Additionally, chPD1-Dap10 induced a central memory T-cell phenotype compared with chPD1-CD28, which induced an effector memory phenotype. The chPD1-Dap10 T cells also had enhanced in vivo persistence and anti-tumour efficacy compared with chPD1-CD28 T cells. Therefore, adoptive transfer of chPD1 T cells could be a novel therapy for lymphoma and inclusion of the Dap10 co-stimulatory domain in chimeric antigen receptors may induce a preferential cytokine profile and T-cell differentiation phenotype for anti-tumour therapies. © 2017 John Wiley & Sons Ltd.

  2. Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

    Science.gov (United States)

    ... Non-Hodgkin Lymphoma Peripheral T-Cell Lymphoma Primary Central Nervous System Lymphoma T-Cell Lymphoma Transformed Mycosis Fungoides Waldenstrom Macroglobulinemia Young Adult Lymphoma Overview Treatment Options Relapsed/Refractory Long-Term ...

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

    Science.gov (United States)

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

    2012-11-01

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

  4. Cerebral lymphoma - CT and MRI diagnostic

    International Nuclear Information System (INIS)

    Popovska, T.; Yanakiev, A.; Zashev, I.

    2012-01-01

    Lymphoma (Hodgkin's and non-Hodgkin's) is a disease of the lymphatic system where the central neural system is affected in very rare cases. According to different authors the frequency of cases with lymphoma where the neural system is affected varies between 0, 2 % and 0, 5 %, and the primary cerebral lymphoma accounts for about 1-2% of ail brain neoplasms. The intracranial form of iymphoma is usually a late onset of the disease with serious and potentially fatal complications for the patient. These complications usually appear several years after diagnosing the disease, but the cerebral lymphoma may occur even in patients who are in remission which is the case with our patient. We present you a case with a 38 -year-old female, who was hospitalized in the Neuro ward with the following complaints -loss of speech for a few minutes, dizziness, weakness, tingling in her right leg as well as shuffling. This patient was diagnosed with histological B-cell non-Hodgkin's lymphoma 8 years ago. CT and MRI were carried out on that patient. Despite both clinical and radiographic suspicions for intracranial forms of lymphoma, the patient was still difficult to diagnose. A definitive diagnosis was given after a surgery and histological examination, i.e. non-Hodgkin's lymphoma - large B-cell lymphoma. This case is of interest because of its rare intracranial localization of the lymphoma. The knowledge of CT and MRI images of the intracranial form of lymphoma may help diagnosing, but images should be interpreted together with the clinical and paraclinical results Hodgkin's and non-Hodgkin's) is a disease of the lymphatic system where the central neural system is affected in very rare cases. According to different authors the frequency of cases with lymphoma where the neural system is affected varies between 0, 2 % and 0, 5 %, and the primary cerebral lymphoma accounts for about 1-2% of ail brain neoplasms. The intracranial form of iymphoma is usually a late onset of the disease

  5. EBV AND HIV-RELATED LYMPHOMA

    Directory of Open Access Journals (Sweden)

    Michele Bibas

    2009-12-01

    Full Text Available HIV-associated lymphoproliferative disorders represent a heterogeneous group of diseases, arising in the presence of HIV-associated immunodeficiency. The overall prevalence of HIV-associated lymphoma is significantly higher compared to that of the general population and it continues to be relevant even after the wide availability of highly active antiretroviral therapy (HAART (1. Moreover, they still represent one of the most frequent cause of death in HIV-infected patients. Epstein–Barr virus (EBV, a γ-Herpesviruses, is involved in human lymphomagenesis, particularly in HIV immunocompromised patients. It has been largely implicated in the development of B-cell lymphoproliferative disorders as Burkitt lymphoma (BL, Hodgkin disease (HD, systemic non Hodgkin lymphoma (NHL, primary central nervous system lymphoma (PCNSL, nasopharyngeal carcinoma (NC. Virus-associated lymphomas are becoming of significant concern for the mortality of long-lived HIV immunocompromised patients, and therefore, research of advanced strategies for AIDS-related lymphomas is an important field in cancer chemotherapy. Detailed understanding of the EBV  lifecycle and related cancers at the molecular level is required for novel strategies of molecular-targeted cancer chemotherapy The linkage of HIV-related lymphoma with EBV infection of the tumor clone has several pathogenetic, prognostic and possibly therapeutic implications which are reviewed herein

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

    Directory of Open Access Journals (Sweden)

    Elisa Rogowitz

    2013-01-01

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

  7. Anticonvulsant profile of a balanced ketogenic diet in acute mouse seizure models.

    Science.gov (United States)

    Samala, Ramakrishna; Willis, Sarah; Borges, Karin

    2008-10-01

    Anticonvulsant effects of the ketogenic diet (KD) have been reported in the mouse, although previous studies did not control for intake of vitamins, minerals and antioxidants. The aim of this study was to examine the effects of balanced ketogenic and control diets in acute mouse seizure models. The behavior in four mouse seizure models, plasma d-beta-hydroxybutyrate (d-BHB) and glucose levels were determined after feeding control diet, 4:1 and 6:1 KDs with matched vitamins, minerals and antioxidants. Feeding 4:1 and 6:1 KDs ad lib to 3-week-old (adolescent) mice resulted in 1.2-2.2mM d-BHB in plasma, but did not consistently change glucose levels. The 6:1 KD reproducibly elevated the CC50 (current that initiates seizures in 50% mice tested) in the 6-Hz model after 14 days of feeding to adolescent CD1 mice. Higher plasma d-BHB levels correlated with anticonvulsant effects. Despite ketosis, no consistent anticonvulsant effects of KDs were found in the fluorothyl or pentylenetetrazole CD1 mouse models. The 4:1 KD was neither anticonvulsant nor neuroprotective in hippocampus in the C3H mouse kainate model. Taken together, the KD's anticonvulsant effect was limited to the 6-Hz model, required chronic feeding with 6:1 fat content, and was independent from lowering plasma glucose.

  8. The STR/ort mouse model of spontaneous osteoarthritis - an update.

    Science.gov (United States)

    Staines, K A; Poulet, B; Wentworth, D N; Pitsillides, A A

    2017-06-01

    Osteoarthritis is a degenerative joint disease and a world-wide healthcare burden. Characterized by cartilage degradation, subchondral bone thickening and osteophyte formation, osteoarthritis inflicts much pain and suffering, for which there are currently no disease-modifying treatments available. Mouse models of osteoarthritis are proving critical in advancing our understanding of the underpinning molecular mechanisms. The STR/ort mouse is a well-recognized model which develops a natural form of osteoarthritis very similar to the human disease. In this Review we discuss the use of the STR/ort mouse in understanding this multifactorial disease with an emphasis on recent advances in its genetics and its bone, endochondral and immune phenotypes. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. MDX-010 in Treating Patients With Recurrent or Refractory Lymphoma

    Science.gov (United States)

    2014-05-22

    Adult Grade III Lymphomatoid Granulomatosis; B-cell Chronic Lymphocytic Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenström Macroglobulinemia

  10. Molecular Pathogenesis of MALT Lymphoma

    Directory of Open Access Journals (Sweden)

    Katharina Troppan

    2015-01-01

    Full Text Available Approximately 8% of all non-Hodgkin lymphomas are extranodal marginal zone B cell lymphoma of mucosa associated lymphoid tissue (MALT, also known as MALT lymphoma, which was first described in 1983 by Isaacson and Wright. MALT lymphomas arise at a wide range of different extranodal sites, with the highest frequency in the stomach, followed by lung, ocular adnexa, and thyroid, and with a low percentage in the small intestine. Interestingly, at least 3 different, apparently site-specific, chromosomal translocations and missense and frameshift mutations, all pathway-related genes affecting the NF-κB signal, have been implicated in the development and progression of MALT lymphoma. However, these genetic abnormalities alone are not sufficient for malignant transformation. There is now increasing evidence suggesting that the oncogenic product of translocation cooperates with immunological stimulation in oncogenesis, that is, the association with chronic bacterial infection or autoaggressive process. This review mainly discusses MALT lymphomas in terms of their genetic aberration and association with chronic infections and summarizes recent advances in their molecular pathogenesis.

  11. Decerebrate mouse model for studies of the spinal cord circuits

    DEFF Research Database (Denmark)

    Meehan, Claire Francesca; Mayr, Kyle A; Manuel, Marin

    2017-01-01

    The adult decerebrate mouse model (a mouse with the cerebrum removed) enables the study of sensory-motor integration and motor output from the spinal cord for several hours without compromising these functions with anesthesia. For example, the decerebrate mouse is ideal for examining locomotor be......, which is ample time to perform most short-term procedures. These protocols can be modified for those interested in cardiovascular or respiratory function in addition to motor function and can be performed by trainees with some previous experience in animal surgery....

  12. Immunohistochemical Profile of Hodgkin and Non-Hodgkin Lymphoma

    International Nuclear Information System (INIS)

    Shahid, R.; Gulzar, R.; Avesi, L.; Hassan, S.; Danish, F.; Mirza, T.

    2016-01-01

    Objective: To analyze the frequencies of histological types of lymphoma, diagnosed with complete immunohistochemical profile in younger and older age group. Study Design: Cross-sectional analytical study. Place and Duration of Study: Dow Diagnostic Research and Reference Laboratory, Dow University of Health Sciences, Karachi, from January 2009 to September 2013. Methodology: Consecutive cases of lymphomas, which were diagnosed using immunohistochemistry, were analyzed according to WHO classification. Frequency and percentages for different types of lymphomas were calculated. Hodgkin and non-Hodgkin lymphomas characteristics in two age groups of less than and more than 40 years were compared, applying chi-square test. Results: Out of the 318 cases, 79 (25 percentage) were Hodgkin Lymphomas (HL) and 239 (75 percentage) were Non-Hodgkin Lymphomas (NHL). Mixed Cellularity Hodgkin Lymphoma (MCHL) was the commonest (n=48). Amongst the NHL, 215 (89.95 percentage) were B cell lymphomas and 24 (10.05percentage) were T-cell lymphomas. Diffuse Large B-Cell Lymphoma (DLBCL) was the commonest lymphoma (n=165, 69.95 percentage of NHL). Anaplastic T-Cell Lymphoma (ALCL, n=10) was the commonest T-cell lymphoma. The frequency of HL was significantly higher in the younger age group and that of NHL was higher in the older age group (p < 0.001). Primary lymph node involvement was reported in 175 (55 percentage) and cervical lymph node was the most frequent site. Extra nodal involvement was seen in 93 (29 percentage) of all cases and was reported in 87 (36.4 percentage) of NHL and 6 (7.5 percentage) of HL. The most common extra nodal site was the gastrointestinal tract. Conclusion: Hodgkin lymphoma comprises 25 percentage and non-Hodgkin lymphoma comprises 75 percentage of all lymphomas. Both occur in younger age groups than reported in the West. B-cell NHL is three times more common than T-cell lymphoma. DLBCL is the most frequent lymphoma. ALCL is the most common T-cell, and mixed

  13. Applying Enhancement Filters in the Pre-processing of Images of Lymphoma

    International Nuclear Information System (INIS)

    Silva, Sérgio Henrique; Do Nascimento, Marcelo Zanchetta; Neves, Leandro Alves; Batista, Valério Ramos

    2015-01-01

    Lymphoma is a type of cancer that affects the immune system, and is classified as Hodgkin or non-Hodgkin. It is one of the ten types of cancer that are the most common on earth. Among all malignant neoplasms diagnosed in the world, lymphoma ranges from three to four percent of them. Our work presents a study of some filters devoted to enhancing images of lymphoma at the pre-processing step. Here the enhancement is useful for removing noise from the digital images. We have analysed the noise caused by different sources like room vibration, scraps and defocusing, and in the following classes of lymphoma: follicular, mantle cell and B-cell chronic lymphocytic leukemia. The filters Gaussian, Median and Mean-Shift were applied to different colour models (RGB, Lab and HSV). Afterwards, we performed a quantitative analysis of the images by means of the Structural Similarity Index. This was done in order to evaluate the similarity between the images. In all cases we have obtained a certainty of at least 75%, which rises to 99% if one considers only HSV. Namely, we have concluded that HSV is an important choice of colour model at pre-processing histological images of lymphoma, because in this case the resulting image will get the best enhancement

  14. The Event Coordination Notation: Behaviour Modelling Beyond Mickey Mouse

    DEFF Research Database (Denmark)

    Jepsen, Jesper; Kindler, Ekkart

    2015-01-01

    The Event Coordination Notation (ECNO) allows modelling the desired behaviour of a software system on top of any object-oriented software. Together with existing technologies from Model-based Software Engineering (MBSE) for automatically generating the software for the structural parts, ECNO allows...... special aspect of ECNO or another; and it would be fair to call them “Mickey Mouse examples”. In this paper, we give a concise overview of the motivation, ideas, and concepts of ECNO. More importantly, we discuss a larger system, which was completely generated from the underlying models: a workflow...... management system. This way, we demonstrate that ECNO can be used for modelling software beyond the typical Mickey Mouse examples. This example demonstrates that the essence of workflow management – including its behaviour – can be captured in ECNO: in a sense, it is a domain model of workflow management...

  15. Pomalidomide and Dexamethasone in Treating Patients With Relapsed or Refractory Primary Central Nervous System Lymphoma or Newly Diagnosed or Relapsed or Refractory Intraocular Lymphoma

    Science.gov (United States)

    2017-08-28

    B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma; Central Nervous System Lymphoma; Intraocular Lymphoma; Primary Diffuse Large B-Cell Lymphoma of the Central Nervous System; Recurrent Adult Diffuse Large Cell Lymphoma; Retinal Lymphoma

  16. Malignant hematopoietic cell lines: in vitro models for the study of natural killer cell leukemia-lymphoma.

    Science.gov (United States)

    Drexler, H G; Matsuo, Y

    2000-05-01

    Malignancies involving natural killer (NK) cells are rare disorders. The complexity of NK cell-involving disorders has only recently been appreciated. Modern classifications discern immature (precursor) from mature NK cell leukemias-lymphomas. Continuous NK leukemia-lymphoma cell lines represent important model systems to study these neoplasms. While there are a number of putative NK cell lines which are, however, either not characterized, not immortalized, non-malignant, non-NK, or plain false cell lines, six bona fide malignant NK cell lines have been established and are sufficiently well characterized: HANK1, KHYG-1, NK-92, NKL, NK-YS and YT. Except for YT which was derived from a not further defined acute lymphoblastic lymphoma, these cell lines were established from patients with various NK cell malignancies. Five of the six cell lines are constitutively interleukin-2-dependent. Their immunoprofile is remarkably similar: CD1-, CD2+, surface CD3 (but cytoplasmic CD3epsilon+), CD4-, CD5-, CD7+, CD8-, CD16-, CD56+, CD57-, TCRalphabeta-, TCRgammadelta-, negative for B cell and myelomonocytic markers. The immunoglobulin heavy chain and T cell receptor genes are all in germline configuration. All six lines show complex chromosomal alterations, with both numerical and structural aberrations, attesting to their malignant and monoclonal nature. Functionally, these cells which contain azurophilic granules in their cytoplasm are nearly universally positive in NK activity assays. Three of five cell lines are Epstein-Barr virus-positive (type II latency). The composite data on these six cell lines allow for the operational definition of a typical malignant NK cell line profile. NK leukemia-lymphoma cell lines will prove invaluable for studies of normal and malignant NK cell biology.

  17. Anti-ICOS Monoclonal Antibody MEDI-570 in Treating Patients With Relapsed or Refractory Peripheral T-cell Lymphoma Follicular Variant or Angioimmunoblastic T-cell Lymphoma

    Science.gov (United States)

    2018-05-09

    Follicular T-Cell Lymphoma; Grade 1 Follicular Lymphoma; Grade 2 Follicular Lymphoma; Grade 3a Follicular Lymphoma; Recurrent Angioimmunoblastic T-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides; Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory Angioimmunoblastic T-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Stage IB Mycosis Fungoides AJCC v7; Stage II Mycosis Fungoides AJCC v7; Stage III Cutaneous T-Cell Non-Hodgkin Lymphoma; Stage III Mycosis Fungoides AJCC v7; Stage IV Cutaneous T-Cell Non-Hodgkin Lymphoma; Stage IV Mycosis Fungoides AJCC v7

  18. Radiotherapy of primary gastric malignant lymphoma

    International Nuclear Information System (INIS)

    Monzen, Yoshio; Mutsukura, Masahide; Moriuchi, Yukiyoshi

    2017-01-01

    Fifteen patients with primary gastric malignant lymphoma who underwent radiotherapy were examined. Median age was 68 years, and male to female ratio was 1:2. All the cases were stage I including 7 cases of diffuse large B-cell lymphoma (DLBCL), 7 cases of MALT lymphoma, and 1 case of follicular lymphoma. Therapy methods were as follows. For DLBCL, 30 Gy of radiotherapy was performed after chemotherapy. For six cases of MALT lymphomas, 30 Gy of radiotherapy was performed. For one patient diagnosed as high-grade gastric MALT lymphoma was treated in the same way as DLBCL. For one patient with follicular lymphoma, 30 Gy of radiotherapy was performed. The radiotherapy was applied with 3-dimensional fixed multi-portal irradiation, with the reduced irradiation of the liver and kidney. There was no recurrence of disease in all cases, and all patients have been alive, and no-recurrence living periods are 20 to 120 months. There was no harmful adverse event, and the tumor had disappeared with 30 Gy of radiation therapy in all cases. Considering the occurrence of secondary cancer, it was considered that a dosage of more than 30 Gy was not necessary for primary gastric malignant lymphoma. (J.P.N.)

  19. cMyc/miR-125b-5p signalling determines sensitivity to bortezomib in preclinical model of cutaneous T-cell lymphomas

    DEFF Research Database (Denmark)

    Manfè, Valentina; Biskup, Edyta; Willumsgaard, Ayalah

    2013-01-01

    Successful/effective cancer therapy in low grade lymphoma is often hampered by cell resistance to anti-neoplastic agents. The crucial mechanisms responsible for this phenomenon are poorly understood. Overcoming resistance of tumor cells to anticancer agents, such as proteasome inhibitors, could...... improve their clinical efficacy. Using cutaneous T-cell lymphoma (CTCL) as a model of the chemotherapy-resistant peripheral lymphoid malignancy, we demonstrated that resistance to proteasome inhibition involved a signaling between the oncogene cMyc and miR-125b-5p. Bortezomib repressed c...

  20. Classification of malignant lymphomas

    International Nuclear Information System (INIS)

    Schneider, M.; Thyss, A.

    1986-01-01

    Malignant lymphomas, primary tumors of the lymphoid tissues, were first described in 1832 by Thomas Hodgkin. The histological characteristics were later defined by Sternberg and Reed, and Virchow introduced the concept of lymphosarcoma in 1863. Today, these pathologies are grouped together under the synonymous terms hematosarcoma or malignant lymphoma, which are in turn divided into Hodgkin's disease (HD) and non-Hodgkin's malignant lymphomas (NHL). The therapy of lymphomas is controversial. The validity of treatment for asymptomatic patients is questioned, owing to the indolent course of many lymphomas. Results for histologically unfavorable forms are highly disparate. Exclusive radiotherapy has occasionally produced up to 78% disease-free survival at 5 years for truly localized stages. Today, however, use of chemotherapy/radiotherapy combinations is almost universal, with chemotherapy occasionally being used alone and providing 90% disease-free survival at 5 years. Chemotherapy is the main treatment for disseminated forms; the major associations include doxorubicin hydrochloride (Adriamycin), cyclophosphamide, vincristine sulfate, methotrexate, and prednisone. Radiotherapy is used more for adjuvant purposes. Synthesis of recent studies allows us to reasonably expect 40% relapse-free survival at 10 years and the establishment of a cure plateau in the near future

  1. Danish National Lymphoma Registry

    DEFF Research Database (Denmark)

    Arboe, Bente; Josefsson, Pär; Jørgensen, Judit

    2016-01-01

    AIM OF DATABASE: The Danish National Lymphoma Registry (LYFO) was established in order to monitor and improve the diagnostic evaluation and the quality of treatment of all lymphoma patients in Denmark. STUDY POPULATION: The LYFO database was established in 1982 as a seminational database including...... all lymphoma patients referred to the departments of hematology. The database became nationwide on January 1, 2000. MAIN VARIABLES: The main variables include both clinical and paraclinical variables as well as details of treatment and treatment evaluation. Up to four forms are completed for each......-100 years) and a male/female ratio of 1.23:1. Patients can be registered with any of 42 different subtypes according to the World Health Organization classifications. CONCLUSION: LYFO is a nationwide database for all lymphoma patients in Denmark and includes detailed information. This information is used...

  2. [Plasmablastic lymphoma].

    Science.gov (United States)

    Fernández-Álvarez, Rubén; Sancho, Juan-Manuel; Ribera, Josep-María

    2016-11-04

    Plasmablastic lymphoma (PBL) is a rare and aggressive subtype of non-Hodgkin lymphoma that commonly occurs in human immunodeficiency virus (HIV)-positive individuals, and affects oral sites. Occasionally, it has been described in HIV-negative patients and involving non-oral sites. Pathologically, PBL is a high-grade B-cell lymphoma that displays the immunophenotype of a terminally differentiated B-lymphocyte with loss of B-cell markers (CD20) and expression of plasma-cell antigens. Epstein-Barr virus infection and MYC rearrangements are frequently observed. Treatment of PBL is challenging because of the lack of established treatment and poor outcomes, with median survival times shorter than one year. In this review, we discuss the clinical and epidemiologic spectrum of PBL as well as its distinct pathological features. Finally, we summarize the currently available approaches for the treatment of patients with PBL. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  3. Synergistic Anti-Tumor Activity of EZH2 Inhibitors and Glucocorticoid Receptor Agonists in Models of Germinal Center Non-Hodgkin Lymphomas.

    Directory of Open Access Journals (Sweden)

    Sarah K Knutson

    Full Text Available Patients with non-Hodgkin lymphoma (NHL are treated today with a cocktail of drugs referred to as CHOP (Cyclophosphamide, Hydroxyldaunorubicin, Oncovin, and Prednisone. Subsets of patients with NHL of germinal center origin bear oncogenic mutations in the EZH2 histone methyltransferase. Clinical testing of the EZH2 inhibitor EPZ-6438 has recently begun in patients. We report here that combining EPZ-6438 with CHOP in preclinical cell culture and mouse models results in dramatic synergy for cell killing in EZH2 mutant germinal center NHL cells. Surprisingly, we observe that much of this synergy is due to Prednisolone - a glucocorticoid receptor agonist (GRag component of CHOP. Dramatic synergy was observed when EPZ-6438 is combined with Prednisolone alone, and a similar effect was observed with Dexamethasone, another GRag. Remarkably, the anti-proliferative effect of the EPZ-6438+GRag combination extends beyond EZH2 mutant-bearing cells to more generally impact germinal center NHL. These preclinical data reveal an unanticipated biological intersection between GR-mediated gene regulation and EZH2-mediated chromatin remodeling. The data also suggest the possibility of a significant and practical benefit of combining EZH2 inhibitors and GRag that warrants further investigation in a clinical setting.

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

    Science.gov (United States)

    2018-06-13

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

  5. Radiotherapy of malignant lymphomas

    Energy Technology Data Exchange (ETDEWEB)

    Kujawska, J [Instytut Onkologii, Krakow (Poland)

    1979-01-01

    The paper discusses current views on the role of radiotherapy in the treatment of patients with malignant lymphomas. Principles of radiotherapy employed in the Institute of Oncology in Cracow in case of patients with malignant lymphomas are also presented.

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

    Directory of Open Access Journals (Sweden)

    Şerife Hülya Arslan

    2012-09-01

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

  7. Hodgkin Lymphoma (For Kids)

    Science.gov (United States)

    ... First Aid & Safety Doctors & Hospitals Videos Recipes for Kids Kids site Sitio para niños How the Body Works ... Educators Search English Español Hodgkin Lymphoma KidsHealth / For Kids / Hodgkin Lymphoma What's in this article? What Is ...

  8. Molecular resemblance of an AIDS-associated lymphoma and endemic Burkitt lymphomas: Implications for their pathogenesis

    International Nuclear Information System (INIS)

    Haluska, F.G.; Russo, G.; Croce, C.M.; Kant, J.; Andreef, M.

    1989-01-01

    Non-Hodgkin lymphoma is a common feature of AIDS. Approximately 30-40% of these tumors exhibit clinical features suggestive of endemic Burkitt lymphoma: they are aggressive malignancies that occur in association with Epstein-Barr virus infection, they arise in the setting of immunosuppression, and they carry t(8;14) translocations without detectable rearrangement of the MYC oncogene. To understand the molecular basis of these parallels, the authors analyzed a case of Epstein-Barr-positive AIDS-associated undifferentiated lymphoma. Southern blots show that the tumor exhibits immunoglobulin joining segment rearrangement but no rearrangement of the MYC oncogene. Cloning of the rearranged joining segment allowed the isolation of recombinant clones encompassing the translocation breakpoint, and sequencing of the translocation junction disclosed that the breakpoint is situated 7 base pairs from the chromosome 14 site involved in a previously described endemic Burkitt lymphoma translocation. Furthermore, the breakpoint is situated far from MYC on chromosome 8, a constant finding in endemic Burkitt lymphomas. That the molecular architecture of the translocation in this case is strikingly similar to previously analyzed translocations from endemic Burkitt lymphomas strongly suggests that common molecular mechanisms must be operative in the pathogenesis of these tumors

  9. Pathology of Mouse Models of Accelerated Aging

    NARCIS (Netherlands)

    Harkema, L.; Youssef, S. A.; de Bruin, A.

    Progeroid mouse models display phenotypes in multiple organ systems that suggest premature aging and resemble features of natural aging of both mice and humans. The prospect of a significant increase in the global elderly population within the next decades has led to the emergence of geroscience,

  10. Pathology of Mouse Models of Accelerated Aging

    NARCIS (Netherlands)

    Harkema, L; Youssef, S A; de Bruin, A

    2016-01-01

    Progeroid mouse models display phenotypes in multiple organ systems that suggest premature aging and resemble features of natural aging of both mice and humans. The prospect of a significant increase in the global elderly population within the next decades has led to the emergence of "geroscience,"

  11. The mouse lymphoma thymidine kinase assay for the assessment and comparison of the mutagenic activity of cigarette mainstream smoke particulate phase.

    Science.gov (United States)

    Schramke, H; Meisgen, T J; Tewes, F J; Gomm, W; Roemer, E

    2006-10-29

    The mouse lymphoma thymidine kinase assay (MLA) has been optimized to quantitatively determine the in vitro mutagenicity of cigarette mainstream smoke particulate phase. To test whether the MLA is able to discriminate between different cigarette types, specially constructed cigarettes each containing a single tobacco type - Bright, Burley, or Oriental - were investigated. The mutagenic activity of the Burley cigarette was statistically significantly lower, up to approximately 40%, than that of the Bright and Oriental cigarettes. To determine the impact of two different sets of smoking conditions, American-blend cigarettes were smoked under US Federal Trade Commission/International Organisation for Standardisation conditions and under Massachusetts Department of Public Health (MDPH) conditions. Conventional cigarettes - eight from the US commercial market plus the Reference Cigarettes 1R4F and 2R4F - and an electrically heated cigarette smoking system (EHCSS) prototype were tested. There were no statistically significant differences between the two sets of smoking conditions on a per mg total particulate matter basis, although there was a consistent trend towards slightly lower mutagenic activity under MDPH conditions. The mutagenic activity of the EHCSS prototype was distinctly lower than that of the conventional cigarettes under both sets of smoking conditions. These results show that the MLA can be used to assess and compare the mutagenic activity of cigarette mainstream smoke particulate phase in the comprehensive toxicological assessment of cigarette smoke.

  12. Genome-Wide Expression Profiling of Five Mouse Models Identifies Similarities and Differences with Human Psoriasis

    Science.gov (United States)

    Swindell, William R.; Johnston, Andrew; Carbajal, Steve; Han, Gangwen; Wohn, Christian; Lu, Jun; Xing, Xianying; Nair, Rajan P.; Voorhees, John J.; Elder, James T.; Wang, Xiao-Jing; Sano, Shigetoshi; Prens, Errol P.; DiGiovanni, John; Pittelkow, Mark R.; Ward, Nicole L.; Gudjonsson, Johann E.

    2011-01-01

    Development of a suitable mouse model would facilitate the investigation of pathomechanisms underlying human psoriasis and would also assist in development of therapeutic treatments. However, while many psoriasis mouse models have been proposed, no single model recapitulates all features of the human disease, and standardized validation criteria for psoriasis mouse models have not been widely applied. In this study, whole-genome transcriptional profiling is used to compare gene expression patterns manifested by human psoriatic skin lesions with those that occur in five psoriasis mouse models (K5-Tie2, imiquimod, K14-AREG, K5-Stat3C and K5-TGFbeta1). While the cutaneous gene expression profiles associated with each mouse phenotype exhibited statistically significant similarity to the expression profile of psoriasis in humans, each model displayed distinctive sets of similarities and differences in comparison to human psoriasis. For all five models, correspondence to the human disease was strong with respect to genes involved in epidermal development and keratinization. Immune and inflammation-associated gene expression, in contrast, was more variable between models as compared to the human disease. These findings support the value of all five models as research tools, each with identifiable areas of convergence to and divergence from the human disease. Additionally, the approach used in this paper provides an objective and quantitative method for evaluation of proposed mouse models of psoriasis, which can be strategically applied in future studies to score strengths of mouse phenotypes relative to specific aspects of human psoriasis. PMID:21483750

  13. An inducible mouse model of late onset Tay-Sachs disease.

    Science.gov (United States)

    Jeyakumar, Mylvaganam; Smith, David; Eliott-Smith, Elena; Cortina-Borja, Mario; Reinkensmeier, Gabriele; Butters, Terry D; Lemm, Thorsten; Sandhoff, Konrad; Perry, V Hugh; Dwek, Raymond A; Platt, Frances M

    2002-08-01

    Mouse models of the G(M2) gangliosidoses, Tay-Sachs and Sandhoff disease, are null for the hexosaminidase alpha and beta subunits respectively. The Sandhoff (Hexb-/-) mouse has severe neurological disease and mimics the human infantile onset variant. However, the Tay-Sachs (Hexa-/-) mouse model lacks an overt phenotype as mice can partially bypass the blocked catabolic pathway and escape disease. We have investigated whether a subset of Tay-Sachs mice develop late onset disease. We have found that approximately 65% of the mice develop one or more clinical signs of the disease within their natural life span (n = 52, P disease at an earlier age (n = 21, P Tay-Sachs mice confirmed that pregnancy induces late onset Tay-Sachs disease. Onset of symptoms correlated with reduced up-regulation of hexosaminidase B, a component of the bypass pathway.

  14. Ultrastructural study of Rift Valley fever virus in the mouse model

    Energy Technology Data Exchange (ETDEWEB)

    Reed, Christopher; Steele, Keith E.; Honko, Anna; Shamblin, Joshua; Hensley, Lisa E. [United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD (United States); Smith, Darci R., E-mail: darci.smith1@us.army.mil [United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD (United States)

    2012-09-15

    Detailed ultrastructural studies of Rift Valley fever virus (RVFV) in the mouse model are needed to develop and characterize a small animal model of RVF for the evaluation of potential vaccines and therapeutics. In this study, the ultrastructural features of RVFV infection in the mouse model were analyzed. The main changes in the liver included the presence of viral particles in hepatocytes and hepatic stem cells accompanied by hepatocyte apoptosis. However, viral particles were observed rarely in the liver; in contrast, particles were extremely abundant in the CNS. Despite extensive lymphocytolysis, direct evidence of viral replication was not observed in the lymphoid tissue. These results correlate with the acute-onset hepatitis and delayed-onset encephalitis that are dominant features of severe human RVF, but suggest that host immune-mediated mechanisms contribute significantly to pathology. The results of this study expand our knowledge of RVFV-host interactions and further characterize the mouse model of RVF.

  15. Ultrastructural study of Rift Valley fever virus in the mouse model

    International Nuclear Information System (INIS)

    Reed, Christopher; Steele, Keith E.; Honko, Anna; Shamblin, Joshua; Hensley, Lisa E.; Smith, Darci R.

    2012-01-01

    Detailed ultrastructural studies of Rift Valley fever virus (RVFV) in the mouse model are needed to develop and characterize a small animal model of RVF for the evaluation of potential vaccines and therapeutics. In this study, the ultrastructural features of RVFV infection in the mouse model were analyzed. The main changes in the liver included the presence of viral particles in hepatocytes and hepatic stem cells accompanied by hepatocyte apoptosis. However, viral particles were observed rarely in the liver; in contrast, particles were extremely abundant in the CNS. Despite extensive lymphocytolysis, direct evidence of viral replication was not observed in the lymphoid tissue. These results correlate with the acute-onset hepatitis and delayed-onset encephalitis that are dominant features of severe human RVF, but suggest that host immune-mediated mechanisms contribute significantly to pathology. The results of this study expand our knowledge of RVFV–host interactions and further characterize the mouse model of RVF.

  16. Epstein-Barr Virus in Classical Hodgkin Lymphoma

    International Nuclear Information System (INIS)

    Azhar, M.; Din, H. U.; Muhammad, I.; Hashmi, S. N.; Akhtar, F.

    2016-01-01

    Background: Epstein-Barr virus plays an important role in pathogenesis of Hodgkin lymphoma. The first patient with Epstein-Barr positive Reed Sternberg cells was described in 1985. Since then association between Epstein-Barr virus and Hodgkin lymphoma has been shown in many parts of the world and its occurrence shows significant variation from continent to continent and from country to country. Method: The study was carried out at department of histopathology, Armed Forces Institute of Pathology from 27th April 2013 to 10th March 2014. A total of 55 cases of classical Hodgkin lymphoma were included in the study. Results: Out of 55 patients, 38 (69 percent) were male and 17 (31 percent) were female. The age of the patients ranged between 4-67 years with an average age of 29.4±21.72 years. Out of these, 44 cases (80 percent) were positive for latent membrane protein-1. Among positive cases 32 (72.72 percent) were male and 12 (27.28 percent) were female. Based upon histological subtypes MCHL was the commonest as a whole accounting for 87.3 percent as well as among both genders. Out of total 55 cases, 79.16 percent (38/48) of mixed cellularity Hodgkin lymphoma cases showed positivity for latent membrane protein-1 while 83.33 percent (5/6) cases of nodular sclerosis Hodgkin lymphoma and 100 percent (1/1) cases of lymphocyte depleted Hodgkin lymphoma showed positivity. No case of lymphocyte predominant classical Hodgkin lymphoma was diagnosed during the study. 80 percent of our classical Hodgkin lymphoma cases showed association with EBV expression. A total of 79.16 percent cases of mixed cellularity Hodgkin lymphoma showed LMP1 expression while 100 percent of lymphocyte depleted Hodgkin lymphoma showed LMP1 expression. Conclusion: The highest expression seen in lymphocyte depleted Hodgkin lymphoma subtype in contrast to mixed cellularity requires to be confirmed by a larger scale study comprising of substantial number of patients of lymphocyte depleted Hodgkin lymphoma

  17. Engineering a new mouse model for vitiligo.

    Science.gov (United States)

    Manga, Prashiela; Orlow, Seth J

    2012-07-01

    Although the precise mechanisms that trigger vitiligo remain elusive, autoimmune responses mediate its progression. The development of therapies has been impeded by a paucity of animal models, since mice lack interfollicular melanocytes, the primary targets in vitiligo. In this issue, Harris et al. describe a mouse model in which interfollicular melanocytes are retained by Kit ligand overexpression and an immune response is initiated by transplanting melanocyte-targeting CD8+ T cells.

  18. Transmission of naturally occurring lymphoma in macaque monkeys.

    OpenAIRE

    Hunt, R D; Blake, B J; Chalifoux, L V; Sehgal, P K; King, N W; Letvin, N L

    1983-01-01

    Spontaneously occurring rhesus monkey lymphomas were transmitted into healthy rhesus monkeys by using tumor cell suspensions. The naturally arising tumors included an immunoblastic sarcoma and an undifferentiated lymphoma. Recipient animals developed undifferentiated lymphomas, poorly differentiated lymphomas, or parenchymal lymphoproliferative abnormalities suggestive of early lesions of lymphoma. Some of these animals developed such opportunistic infections as cytomegalovirus hepatitis and ...

  19. Taltirelin alleviates fatigue-like behavior in mouse models of cancer-related fatigue.

    Science.gov (United States)

    Dougherty, John P; Wolff, Brian S; Cullen, Mary J; Saligan, Leorey N; Gershengorn, Marvin C

    2017-10-01

    Fatigue affects most cancer patients and has numerous potential causes, including cancer itself and cancer treatment. Cancer-related fatigue (CRF) is not relieved by rest, can decrease quality of life, and has no FDA-approved therapy. Thyrotropin-releasing hormone (TRH) has been proposed as a potential novel treatment for CRF, but its efficacy against CRF remains largely untested. Thus, we tested the TRH analog, taltirelin (TAL), in mouse models of CRF. To model fatigue, we used a mouse model of chemotherapy, a mouse model of radiation therapy, and mice bearing colon 26 carcinoma tumors. We used the treadmill fatigue test to assess fatigue-like behavior after treatment with TAL. Additionally, we used wild-type and TRH receptor knockout mice to determine which TRH receptor was necessary for the actions of TAL. Tumor-bearing mice displayed muscle wasting and all models caused fatigue-like behavior, with mice running a shorter distance in the treadmill fatigue test than controls. TAL reversed fatigue-like behavior in all three models and the mouse TRH 1 receptor was necessary for the effects of TAL. These data suggest that TAL may be useful in alleviating fatigue in all cancer patients and provide further support for evaluating TAL as a potential therapy for CRF in humans. Published by Elsevier Ltd.

  20. The Four types of Tregs in malignant lymphomas

    Directory of Open Access Journals (Sweden)

    Wang Jing

    2011-12-01

    Full Text Available Abstract Regulatory T cells (Tregs are a specialized subpopulation of CD4+ T cells, which act to suppress the activation of other immune cells. Tregs represent important modulators for the interaction between lymphomas and host microenvironment. Lymphomas are a group of serious and frequently fatal malignant diseases of lymphocytes. Recent studies revealed that some lymphoma T cells might adopt a Treg profile. Assessment of Treg phenotypes and genotypes in patients may offer prediction of outcome in many types of lymphomas including diffuse large B-cell lymphoma, follicular lymphoma, cutaneous T cell lymphoma, and Hodgkin's lymphoma. Based on characterized roles of Tregs in lymphomas, we can categorize the various roles into four groups: (a suppressor Tregs; (b malignant Tregs; (c direct tumor-killing Tregs; and (d incompetent Tregs. The classification into four groups is significant in predicting prognosis and designing Tregs-based immunotherapies for treating lymphomas. In patients with lymphomas where Tregs serve either as suppressor Tregs or malignant Tregs, anti-tumor cytotoxicity is suppressed thus decreased numbers of Tregs are associated with a good prognosis. In contrast, in patients with lymphomas where Tregs serve as tumor-killing Tregs and incompetent Tregs, anti-tumor cytotoxicity is enhanced or anti-autoimmune Tregs activities are weakened thus increased numbers of Tregs are associated with a good prognosis and reduced numbers of Tregs are associated with a poor prognosis. However, the mechanisms underlying the various roles of Tregs in patients with lymphomas remain unknown. Therefore, further research is needed in this regard as well as the utility of Tregs as prognostic factors and therapy strategies in different lymphomas.

  1. Cardiac disease and arrhythmogenesis: Mechanistic insights from mouse models

    Directory of Open Access Journals (Sweden)

    Lois Choy

    2016-09-01

    Full Text Available The mouse is the second mammalian species, after the human, in which substantial amount of the genomic information has been analyzed. With advances in transgenic technology, mutagenesis is now much easier to carry out in mice. Consequently, an increasing number of transgenic mouse systems have been generated for the study of cardiac arrhythmias in ion channelopathies and cardiomyopathies. Mouse hearts are also amenable to physical manipulation such as coronary artery ligation and transverse aortic constriction to induce heart failure, radiofrequency ablation of the AV node to model complete AV block and even implantation of a miniature pacemaker to induce cardiac dyssynchrony. Last but not least, pharmacological models, despite being simplistic, have enabled us to understand the physiological mechanisms of arrhythmias and evaluate the anti-arrhythmic properties of experimental agents, such as gap junction modulators, that may be exert therapeutic effects in other cardiac diseases. In this article, we examine these in turn, demonstrating that primary inherited arrhythmic syndromes are now recognized to be more complex than abnormality in a particular ion channel, involving alterations in gene expression and structural remodelling. Conversely, in cardiomyopathies and heart failure, mutations in ion channels and proteins have been identified as underlying causes, and electrophysiological remodelling are recognized pathological features. Transgenic techniques causing mutagenesis in mice are extremely powerful in dissecting the relative contributions of different genes play in producing disease phenotypes. Mouse models can serve as useful systems in which to explore how protein defects contribute to arrhythmias and direct future therapy.

  2. Primary intracerebral lymphoma: Case report

    Directory of Open Access Journals (Sweden)

    Olcay Eser

    2012-09-01

    Full Text Available We describe a case of primary central nervous lymphoma (PCNSL that may be confused with magnetic resonance imaging (MRI findings of high grade glioma. Primary central nervous lymphoma is a rare tumour and it account for 0.3-3% of intracranial tumours. A 61 year’s old woman was admitted to our clinic with a severe headache, vomiting, left hemiparesia and transient loss of consciousness. Primary central nervous lymphoma may show various biological and radiological characteristics. We herein emphasized being confused with MRI findings of PCNSL and high grade glioma. J Clin Exp Invest 2012; 3 (3: 409-411Key words: Primary central nervous lymphoma, high grade glioma, B-cell, diagnosis

  3. Olfaction in three genetic and two MPTP-induced Parkinson's disease mouse models.

    Directory of Open Access Journals (Sweden)

    Stefan Kurtenbach

    Full Text Available Various genetic or toxin-induced mouse models are frequently used for investigation of early PD pathology. Although olfactory impairment is known to precede motor symptoms by years, it is not known whether it is caused by impairments in the brain, the olfactory epithelium, or both. In this study, we investigated the olfactory function in three genetic Parkinson's disease (PD mouse models and mice treated with MPTP intraperitoneally and intranasally. To investigate olfactory function, we performed electro-olfactogram recordings (EOGs and an olfactory behavior test (cookie-finding test. We show that neither a parkin knockout mouse strain, nor intraperitoneal MPTP treated animals display any olfactory impairment in EOG recordings and the applied behavior test. We also found no difference in the responses of the olfactory epithelium to odorants in a mouse strain over-expressing doubly mutated α-synuclein, while this mouse strain was not suitable to test olfaction in a cookie-finding test as it displays a mobility impairment. A transgenic mouse expressing mutated α-synuclein in dopaminergic neurons performed equal to control animals in the cookie-finding test. Further we show that intranasal MPTP application can cause functional damage of the olfactory epithelium.

  4. Lymphoma cytogenetics.

    Science.gov (United States)

    Dave, Bhavana J; Nelson, Marilu; Sanger, Warren G

    2011-12-01

    Lymphomas are a heterogeneous group of neoplasms with distinct morphologic, immunologic, and cytogenetic characteristics. Overlapping morphologic and immunophenotypic features often makes accurate diagnosis difficult. Cytogenetics helps simplify the diagnostic complexities presented in transforming and progressive lymphoid malignancies. Genetic studies using technical advances such as fluorescence in situ hybridization and the newer approaches of array comparative genomic hybridization and gene expression profiling play a critical and often defining role in the diagnosis, progression, prognosis, and therapeutic stratification. This article reviews characteristic cytogenetic abnormalities in specific subtypes of lymphomas at diagnosis, disease progression, and prognosis.

  5. TL transgenic mouse strains

    International Nuclear Information System (INIS)

    Obata, Y.; Matsudaira, Y.; Hasegawa, H.; Tamaki, H.; Takahashi, T.; Morita, A.; Kasai, K.

    1993-01-01

    As a result of abnormal development of the thymus of these mice, TCR αβ lineage of the T cell differentiation is disturbed and cells belonging to the TCR γδ CD4 - CD8 - double negative (DN) lineage become preponderant. The γδ DN cells migrate into peripheral lymphoid organs and constitute nearly 50% of peripheral T cells. Immune function of the transgenic mice is severely impaired, indicating that the γδ cells are incapable of participating in these reactions. Molecular and serological analyses of T-cell lymphomas reveal that they belong to the γδ lineage. Tg.Tla a -3-1 mice should be useful in defining the role of TL in normal and abnormal T cell differentiation as well as in the development of T-cell lymphomas, and further they should facilitate studies on the differentiation and function of γδ T cells. We isolated T3 b -TL gene from B6 mice and constructed a chimeric gene in which T3 b -TL is driven by the promoter of H-2K b . With the chimeric gene, two transgenic mouse strains, Tg. Con.3-1 and -2 have been derived in C3H background. Both strains express TL antigen in various tissues including skin. The skin graft of transgenic mice on C3H and (B6 X C3H)F 1 mice were rejected. In the mice which rejected the grafts, CD8 + TCRαβ cytotoxic T cells (CTL) against TL antigens were recognized. The recognition of TL by CTL did not require the antigen presentation by H-2 molecules. The results indicated that TL antigen in the skin becomes a transplantation antigen and behaves like a typical allogeneic MHC class I antigen. The facts that (B6 X C3H)F 1 mice rejected the skin expressing T3 b -TL antigen and induced CTL that killed TL + lymphomas of B6 origin revealed that TL antigen encoded by T3 b -TL is recognized as non-self in B6 mice. Experiments are now extended to analyze immune responses to TL antigen expressed on autochthonous T cell lymphomas. (J.P.N.)

  6. Radiotherapy of adult nodal non Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    Gamen, G.; Thirion, P.

    1999-01-01

    The role of radiotherapy in the treatment of nodal non-Hodgkin's lymphoma has been modified by the introduction of efficient chemotherapy and the development of different pathological classifications. The recommended treatment of early-stage aggressive lymphomas is primarily a combination chemotherapy. The interest of adjuvant radiotherapy remains unclear and has to be established through large prospective trials. If radiation therapy has to be delivered, the historical results of exclusive radiation therapy showed that involved-fields and a dose of 35-40 Gy (daily fraction of 1.8 Gy, 5 days a week) are the optimal schedule. The interest of radiotherapy in the treatment of advanced-stage aggressive lymphoma is yet to be proven. Further studies had to stratify localized stages according to the factors of the International Prognostic Index. For easy-stage low-grade lymphoma, radiotherapy remains the standard treatment. However, the appropriate technique to use is controversial. Involved-field irradiation at a dose of 35 Gy seems to be the optimal schedule, providing a 10 year disease-free survival rate of 50 % and no major toxicity. There is no standard indication of radiotherapy in the treatment advanced-stage low-grade lymphoma. For 'new' nodal lymphoma's types, the indication of radiotherapy cannot be established (mantle-zone lymphoma, marginal zone B-cell lymphoma) or must take into account the natural history (Burkitt's lymphoma, peripheral T-cell lymphoma) and the sensibility to others therapeutic methods. (authors)

  7. Ocular Adnexal Follicular Lymphoma

    DEFF Research Database (Denmark)

    Rasmussen, Peter K; Coupland, Sarah E; Finger, Paul T

    2014-01-01

    that involved 6 eye cancer centers from January 1, 1980, through December 31, 2010. A total of 105 patients with follicular OAL were identified, of which 7 patients were excluded because of missing clinical data. The median follow-up time was 52 months (range, 13-118 months). MAIN OUTCOMES AND MEASURES Overall...... in conjunction with a concurrent systemic lymphoma, and 10 (10%) presented with an ocular adnexal relapse. The lacrimal gland (28%), conjunctiva (28%), and orbit (28%) were the most frequently involved sites. Of the 69 patients with primary follicular lymphoma, 38 (55%) presented with Ann Arbor stage IE lymphoma...

  8. Responses of the L51781Y tk/sup +//tk/sup -/ mouse lymphoma cell forward mutation assay: III. 72 coded chemicals

    Energy Technology Data Exchange (ETDEWEB)

    McGregor, D.B.; Brown, A.; Cattanach, P.; Edwards, I.; McBride, D.; Riach, C.; Caspary, W.J.

    1988-01-01

    Seventy-two chemicals were tested for their mutagenic potential in the L51781Y tk/sup +///sup -/ mouse lymphoma cell forward mutation assay, using procedures based upon those described previously. Cultures were exposed to the chemicals for 4 hr, then cultured for 2 days before planting in soft agar with or without trifluorothymidine (TFT), 3 ..mu..g/ml. The chemicals were tested at least twice. Significant responses were obtained with allyl isothiocyanate, p-benzoquinone dioxime, benzyl acetate, 2-biphenylamine HCl, bis(2-chloro-1-methylethyl)ether, cadmium chloride, chlordane, chlorobenzene, chlorobenzilate, 2-chloroethanol, chlorothalonil, cytarabine x HCl, p,p'-DDE, diazinon, 2,6-dichloro-p-phenylenediamine, N,N-diethylthiourea, diglycidylresorcinol ether, 2,4-dimethoxy aniline x HCl, disperse yellow 3, endosulfan, 1,2-epoxyhexadecane, ethyl acrylate, ethyl benzene, ethylene thiourea, F D and C yellow Number 6, furan, heptachlor, isophorone, mercuric chloride, 4,4'-methylenedianiline x 2 HCl, methyl viologen, nickel sulfate x 6H/sub 2/O, 4,4'-oxydianiline, pentachloroethane, piperonyl butoxide, propyl gallate, quinoline, rotenone, 2,4,5,6-tetrachloro-4-nitro-anisole, 1,1,1,2-tetrachloroethane, trichlorfon, 2,4,6-trichlorophenol, 2,4,5-trimethoxybenzaldehyde, 1,1,3-trimethyl-2-thiourea, 1-vinyl-3-cyclopetene dioxide, vinyl toluene, and ziram. The assay was incapable of providing a clear indication of whether some chemicals were mutagens; these benzyl alcohol, 1,4-dichlorobenzene, phenol, succinic acid-2,2-dimethyl hydrazide, and toluene.

  9. Quantitative trait loci affecting phenotypic variation in the vacuolated lens mouse mutant, a multigenic mouse model of neural tube defects

    NARCIS (Netherlands)

    Korstanje, Ron; Desai, Jigar; Lazar, Gloria; King, Benjamin; Rollins, Jarod; Spurr, Melissa; Joseph, Jamie; Kadambi, Sindhuja; Li, Yang; Cherry, Allison; Matteson, Paul G.; Paigen, Beverly; Millonig, James H.

    Korstanje R, Desai J, Lazar G, King B, Rollins J, Spurr M, Joseph J, Kadambi S, Li Y, Cherry A, Matteson PG, Paigen B, Millonig JH. Quantitative trait loci affecting phenotypic variation in the vacuolated lens mouse mutant, a multigenic mouse model of neural tube defects. Physiol Genomics 35:

  10. EBV-positive B cell cerebral lymphoma 12 years after sex-mismatched kidney transplantation: post-transplant lymphoproliferative disorder or donor-derived lymphoma?

    LENUS (Irish Health Repository)

    Phelan, Paul J

    2010-06-01

    We present a follow-up case report of possible transmission of lymphoma 12 years after deceased-donor renal transplantation from a male donor who was found at autopsy to have had an occult lymphoma. The female recipient underwent prompt transplant nephrectomy. However, 12 years later, she presented with cerebral B cell lymphoma. A donor origin for the cerebral lymphoma was supported by in situ hybridization demonstration of a Y chromosome in the lymphoma. There was a dramatic resolution of the cerebral lesions with tapering of immunosuppression and introduction of rituximab treatment. The finding of a Y chromosome in the cerebral lymphoma does not exclude a host contribution to lymphoma development.

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

    Science.gov (United States)

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

    2017-07-01

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

  12. Modern radiation therapy for primary cutaneous lymphomas

    DEFF Research Database (Denmark)

    Specht, Lena; Dabaja, Bouthaina; Illidge, Tim

    2015-01-01

    Primary cutaneous lymphomas are a heterogeneous group of diseases. They often remain localized, and they generally have a more indolent course and a better prognosis than lymphomas in other locations. They are highly radiosensitive, and radiation therapy is an important part of the treatment......, either as the sole treatment or as part of a multimodality approach. Radiation therapy of primary cutaneous lymphomas requires the use of special techniques that form the focus of these guidelines. The International Lymphoma Radiation Oncology Group has developed these guidelines after multinational...... meetings and analysis of available evidence. The guidelines represent an agreed consensus view of the International Lymphoma Radiation Oncology Group steering committee on the use of radiation therapy in primary cutaneous lymphomas in the modern era....

  13. Nonspecific airway reactivity in a mouse model of asthma

    Energy Technology Data Exchange (ETDEWEB)

    Collie, D.D.; Wilder, J.A.; Bice, D.E.

    1995-12-01

    Animal models are indispensable for studies requiring an intact immune system, especially for studying the pathogenic mechanisms in atopic diseases, regulation of IgE production, and related biologic effects. Mice are particularly suitable and have been used extensively for such studies because their immune system is well characterized. Further, large numbers of mutants or inbred strains of mice are available that express deficiencies of individual immunologic processes, inflammatory cells, or mediator systems. By comparing reactions in such mice with appropriate control animals, the unique roles of individual cells or mediators may be characterized more precisely in the pathogenesis of atopic respiratory diseases including asthma. However, given that asthma in humans is characterized by the presence of airway hyperresponsiveness to specific and nonspecific stimuli, it is important that animal models of this disease exhibit similar physiologic abnormalities. In the past, the size of the mouse has limited its versatility in this regard. However, recent studies indicate the feasibility of measuring pulmonary responses in living mice, thus facilitating the physiologic evaluation of putative mouse models of human asthma that have been well charcterized at the immunologic and patholigic level. Future work will provide details of the morphometry of the methacholine-induced bronchoconstriction and will further seek to determine the relationship between cigarette smoke exposure and the development of NS-AHR in the transgenic mouse model.

  14. Mouse Models Recapitulating Human Adrenocortical Tumors: What is lacking?

    Directory of Open Access Journals (Sweden)

    Felicia Leccia

    2016-07-01

    Full Text Available Adrenal cortex tumors are divided into benign forms such as primary hyperplasias and adrenocortical adenomas (ACAs, and malignant forms or adrenocortical carcinomas (ACCs. Primary hyperplasias are rare causes of ACTH-independent hypercortisolism. ACAs are the most common type of adrenal gland tumors and they are rarely functional, i.e producing steroids. When functional, adenomas result in endocrine disorders such as Cushing’s syndrome (hypercortisolism or Conn’s syndrome (hyperaldosteronism. In contrast, ACCs are extremely rare but highly aggressive tumors that may also lead to hypersecreting syndromes. Genetic analyses of patients with sporadic or familial forms of adrenocortical tumors led to the identification of potentially causative genes, most of them being involved in PKA, Wnt/β-catenin and P53 signaling pathways. Development of mouse models is a crucial step to firmly establish the functional significance of candidate genes, to dissect mechanisms leading to tumors and endocrine disorders and in fine to provide in vivo tools for therapeutic screens. In this article we will provide an overview on the existing mouse models (xenografted and genetically engineered of adrenocortical tumors by focusing on the role of PKA and Wnt/β-catenin pathways in this context. We will discuss the advantages and limitations of models that have been developed heretofore and we will point out necessary improvements in the development of next generation mouse models of adrenal diseases.

  15. Spallanzani's mouse: a model of restoration and regeneration.

    Science.gov (United States)

    Heber-Katz, E; Leferovich, J M; Bedelbaeva, K; Gourevitch, D

    2004-01-01

    The ability to regenerate is thought to be a lost phenotype in mammals, though there are certainly sporadic examples of mammalian regeneration. Our laboratory has identified a strain of mouse, the MRL mouse, which has a unique capacity to heal complex tissue in an epimorphic fashion, i.e., to restore a damaged limb or organ to its normal structure and function. Initial studies using through-and-through ear punches showed rapid full closure of the ear holes with cartilage growth, new hair follicles, and normal tissue architecture reminiscent of regeneration seen in amphibians as opposed to the scarring usually seen in mammals. Since the ear hole closure phenotype is a quantitative trait, this has been used to show-through extensive breeding and backcrossing--that the trait is heritable. Such analysis reveals that there is a complex genetic basis for this trait with multiple loci. One of the major phenotypes of the MRL mouse is a potent remodeling response with the absence or a reduced level of scarring. MRL healing is associated with the upregulation of the metalloproteinases MMP-2 and MMP-9 and the downregulation of their inhibitors TIMP-2 and TIMP-3, both present in inflammatory cells such as neutrophils and macrophages. This model has more recently been extended to the heart. In this case, a cryoinjury to the right ventricle leads to near complete scarless healing in the MRL mouse whereas scarring is seen in the control mouse. In the MRL heart, bromodeoxyuridine uptake by cardiomyocytes filling the wound site can be seen 60 days after injury. This does not occur in the control mouse. Function in the MRL heart, as measured by echocardiography, returns to normal.

  16. Follicular non-Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    Hayashi, D.; Lee, J.C.; Devenney-Cakir, B.; Zaim, S.; Ounadjela, S.; Solal-Celigny, P.; Juweid, M.; Guermazi, A.

    2010-01-01

    Follicular non-Hodgkin's lymphoma (NHL) is a unique subtype of NHL, which is indolent, incurable with a high prevalence of residual mass after treatment, and may transform to more aggressive NHL. The aim of this review is to (1) describe the histological and flow cytometry characteristics of follicular NHL; (2) introduce the Follicular Lymphoma International Prognostic Index 2 (FLIPI-2), which allows better treatment selection and patient stratification for clinical trials; (3) illustrate the classic and atypical ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and positron-emission tomography (PET)/CT appearance of follicular NHL; and (4) characterize the appearance of nodal and extranodal follicular NHL with pathological correlation. Imaging is essential in every step of the management of patients with follicular lymphoma. Overall survival is improved with better predictive tools and new targeted biological therapies. Radiologists should be aware of possible active residual mass, indolent recurrence, transformation, and association with other primary cancers in patients treated for follicular lymphoma.

  17. A chimeric human-mouse model of Sjögren's syndrome.

    Science.gov (United States)

    Young, Nicholas A; Wu, Lai-Chu; Bruss, Michael; Kaffenberger, Benjamin H; Hampton, Jeffrey; Bolon, Brad; Jarjour, Wael N

    2015-01-01

    Despite recent advances in the understanding of Sjögren's Syndrome (SjS), the pathogenic mechanisms remain elusive and an ideal model for early drug discovery is not yet available. To establish a humanized mouse model of SjS, peripheral blood mononuclear cells (PBMCs) from healthy volunteers or patients with SjS were transferred into immunodeficient NOD-scid IL-2rγ(null) mouse recipients to produce chimeric mice. While no difference was observed in the distribution of cells, chimeric mice transferred with PBMCs from SjS patients produced enhanced cytokine levels, most significantly IFN-γ and IL-10. Histological examination revealed enhanced inflammatory responses in the lacrimal and salivary glands of SjS chimeras, as measured by digital image analysis and blinded histopathological scoring. Infiltrates were primarily CD4+, with minimal detection of CD8+ T-cells and B-cells. These results demonstrate a novel chimeric mouse model of human SjS that provides a unique in vivo environment to test experimental therapeutics and investigate T-cell disease pathology. Copyright © 2014. Published by Elsevier Inc.

  18. Treatment options for ocular adnexal lymphoma (OAL

    Directory of Open Access Journals (Sweden)

    Victoria Mary Lendrum Cohen

    2009-11-01

    Full Text Available Victoria Mary Lendrum CohenSt. Bartholomew’s and Moorfields Eye Hospital, London UKAbstract: Most lymphomas that involve the ocular adnexal structure are low grade, B cell, non-Hodgkin’s lymphomas. The treatment depends upon the grade and stage of the disease. High grade lymhoma requires treatment with systemic chemotherapy whereas the localized low grade (extranodal marginal zone lymphoma can be successfully managed with local radiotherapy. Chlamydia psittaci infection is associated with low grade ocular lymphoma; however there is wide geographic variation in the strength of this association. Blanket antibiotic therapy is not advised unless there is proof of an infective agent. The monoclonal antibody, rituximab, may be successful for CD20 positive lymphoma, although it is likely that rituximab will have better long-term results when used in combination with systemic chemotherapy.Keywords: ocular adnexal lymphoma, mucosa associated lymphoid tissue, extranodal marginal zone lymphoma, Chlamydia psittaci, rituximab, radiotherapy, chemotherapy

  19. Human herpesvirus 8-associated lymphoma mimicking cutaneous anaplastic large T-cell lymphoma in a patient with human immunodeficiency virus infection.

    Science.gov (United States)

    Li, Meng-Fang; Hsiao, Cheng-Hsiang; Chen, Yi-Lin; Huang, Wen-Ya; Lee, Yi-Hsuan; Huang, Hsien-Neng; Lien, Huang-Chun

    2012-02-01

    Primary effusion lymphoma, a human herpesvirus 8 (HHV8)-associated lymphoma, is uncommon, and it is usually seen in human immunodeficiency virus (HIV)-infected patients. It presents as a body cavity-based lymphomatous effusion, but several cases of the so-called solid primary effusion lymphoma presenting as solid tumors without associated lymphomatous effusion have been reported. They have similar clinical, histopathological and immunophenotypical features. Most of them have a B-cell genotype. This suggests the solid variant may represent a clinicopathological spectrum of primary effusion lymphoma. We report a case of HHV8-associated lymphoma histopathologically and immunophenotypically mimicking cutaneous anaplastic large cell lymphoma. The patient was a 31-year-old HIV-seropositive man presenting with skin nodules over his right thigh. Biopsy of the nodules showed anaplastic large cells infiltrating the dermis. These malignant cells strongly expressed CD3, CD30 and CD43. Cutaneous anaplastic large T-cell lymphoma was initially diagnosed, but further tests, including immunoreactivity for HHV8 protein and clonal rearrangements of immunoglobulin genes, confirmed the diagnosis of HHV8-associated B-cell lymphoma with aberrant T-cell marker expression. This case provides an example of solid primary effusion lymphoma mimicking cutaneous anaplastic large T-cell lymphoma and highlights the importance of HHV8 immunohistochemistry and molecular tests in the diagnosis of HHV8-associated lymphoma with a cutaneous presentation. Copyright © 2011 John Wiley & Sons A/S.

  20. Stereotyped patterns of B-cell receptor in splenic marginal zone lymphoma

    KAUST Repository

    Zibellini, S.

    2010-05-29

    Antigen stimulation may be important for splenic marginal zone lymphoma pathogenesis. To address this hypothesis, the occurrence of stereotyped B-cell receptors was investigated in 133 SMZL (26 HCV+) compared with 4,414 HCDR3 sequences from public databases. Sixteen SMZL (12%) showed stereotyped BCR; 7 of 86 (8%) SMZL sequences retrieved from public databases also belonged to stereotyped HCDR3 subsets. Three categories of subsets were identified: i) SMZL-specific subsets (n=5), composed only of 12 SMZL (9 HCV- from our series); ii) Non-Hodgkin\\'s lymphoma-like subsets (n=5), comprising 5 SMZL (4 from our series) clustering with other indolent lymphomas; iii) "CLL-like subsets" (n=6), comprising 6 SMZL (3 from our series) that belonged to known CLL subsets (n=4) or clustered with public CLL sequences. Immunoglobulin 3D modeling of 3 subsets revealed similarities in antigen binding regions not limited to HCDR3. Overall, data suggest that the pathogenesis of splenic marginal zone lymphoma may involve also HCV unrelated epitopes or an antigenic trigger common to other indolent lymphomas. ©2010 Ferrata Storti Foundation.

  1. Stereotyped patterns of B-cell receptor in splenic marginal zone lymphoma

    KAUST Repository

    Zibellini, S.; Capello, D.; Forconi, F.; Marcatili, P.; Rossi, D.; Rattotti, S.; Franceschetti, S.; Sozzi, E.; Cencini, E.; Marasca, R.; Baldini, L.; Tucci, A.; Bertoni, F.; Passamonti, F.; Orlandi, E.; Varettoni, M.; Merli, M.; Rizzi, S.; Gattei, V.; Tramontano, A.; Paulli, M.; Gaidano, G.; Arcaini, L.

    2010-01-01

    Antigen stimulation may be important for splenic marginal zone lymphoma pathogenesis. To address this hypothesis, the occurrence of stereotyped B-cell receptors was investigated in 133 SMZL (26 HCV+) compared with 4,414 HCDR3 sequences from public databases. Sixteen SMZL (12%) showed stereotyped BCR; 7 of 86 (8%) SMZL sequences retrieved from public databases also belonged to stereotyped HCDR3 subsets. Three categories of subsets were identified: i) SMZL-specific subsets (n=5), composed only of 12 SMZL (9 HCV- from our series); ii) Non-Hodgkin's lymphoma-like subsets (n=5), comprising 5 SMZL (4 from our series) clustering with other indolent lymphomas; iii) "CLL-like subsets" (n=6), comprising 6 SMZL (3 from our series) that belonged to known CLL subsets (n=4) or clustered with public CLL sequences. Immunoglobulin 3D modeling of 3 subsets revealed similarities in antigen binding regions not limited to HCDR3. Overall, data suggest that the pathogenesis of splenic marginal zone lymphoma may involve also HCV unrelated epitopes or an antigenic trigger common to other indolent lymphomas. ©2010 Ferrata Storti Foundation.

  2. Rapid genetic algorithm optimization of a mouse computational model: Benefits for anthropomorphization of neonatal mouse cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Corina Teodora Bot

    2012-11-01

    Full Text Available While the mouse presents an invaluable experimental model organism in biology, its usefulness in cardiac arrhythmia research is limited in some aspects due to major electrophysiological differences between murine and human action potentials (APs. As previously described, these species-specific traits can be partly overcome by application of a cell-type transforming clamp (CTC to anthropomorphize the murine cardiac AP. CTC is a hybrid experimental-computational dynamic clamp technique, in which a computationally calculated time-dependent current is inserted into a cell in real time, to compensate for the differences between sarcolemmal currents of that cell (e.g., murine and the desired species (e.g., human. For effective CTC performance, mismatch between the measured cell and a mathematical model used to mimic the measured AP must be minimal. We have developed a genetic algorithm (GA approach that rapidly tunes a mathematical model to reproduce the AP of the murine cardiac myocyte under study. Compared to a prior implementation that used a template-based model selection approach, we show that GA optimization to a cell-specific model results in a much better recapitulation of the desired AP morphology with CTC. This improvement was more pronounced when anthropomorphizing neonatal mouse cardiomyocytes to human-like APs than to guinea pig APs. CTC may be useful for a wide range of applications, from screening effects of pharmaceutical compounds on ion channel activity, to exploring variations in the mouse or human genome. Rapid GA optimization of a cell-specific mathematical model improves CTC performance and may therefore expand the applicability and usage of the CTC technique.

  3. Imaging of primary pediatric lymphoma of bone

    International Nuclear Information System (INIS)

    Milks, Kathryn S.; McLean, Thomas W.; Anthony, Evelyn Y.

    2016-01-01

    Primary pediatric bone lymphoma is a rare form of non-Hodgkin lymphoma. Unlike nodal forms of lymphoma, imaging abnormalities in lymphoma of bone do not resolve rapidly in conjunction with treatment and radiologic findings can remain abnormal for years, making it difficult to evaluate treatment response. To evaluate the utility of imaging in assessment of patients with primary pediatric bone lymphoma. At our institution between 2004 and 2013, six cases of pathology-proven primary pediatric bone lymphoma were diagnosed. Retrospective chart review was performed to assess imaging utilization. Our data were qualitatively compared with existing literature to construct an algorithm for imaging patients with primary lymphoma of bone. Imaging evaluation of patients with primary pediatric bone lymphoma was highly variable at our institution. Conventional imaging was routinely used to evaluate response to treatment, despite lack of appreciable osseous change. Imaging in the absence of symptoms did not alter clinical management. Only positron emission tomography CT (PET/CT) proved capable of demonstrating imaging changes from the pretreatment to the post-treatment scans that were consistent with the clinical response to treatment. Surveillance imaging is likely unnecessary in patients with a known diagnosis of pediatric lymphoma of bone. Pretreatment and post-treatment PET/CT is likely sufficient to assess response. There is little data to support the use of interim and surveillance PET/CT. (orig.)

  4. PET CT and lymphomas

    International Nuclear Information System (INIS)

    Castro, R.

    2012-01-01

    This presentation is about Tc and lymphomas. Classification and clinical cases of various cancer such as gastro duodenal or ulcer, mama, medullary, lymph and neck, leukemia, nodular sclerosis. Metabolic information, anatomical nature of lymphoma and its clinical presentation determine the extent that PET should be used in the patient.

  5. Radiological characteristics of AIDS- related lymphoma

    International Nuclear Information System (INIS)

    Ramos, Gloria Maria Martins G.; Marchiori, Edson

    1996-01-01

    The epidemic of acquired immunodeficiency syndrome (AIDS) increased the incidence of lymphoma, particularly the non-Hodgkin's lymphoma. The lymphoma in immune deficient patients is usually high-grade, very aggressive and with poor prognostic. We report the radiologic characteristics of AIDS-related lymphoma in 19 patients and correlate with the literature. The disease was predominant in homosexual male patients, with mean age of 38 years. The radiological characteristics are nonspecific to differential diagnosis, but we must suspect of lymphoma. We found ring-enhanced lesions in the radiologic studies of central nervous system. Hylar and mediastinal lymphadenopath, nodules and alveolar infiltration were detected on thoracic examinations. Abdominal examinations showed hepatosplenomegaly, lymphadenopathy, hepatic focal lesions and thickneded with distorted mucosa in the alimentary tract. Bone involvement presented as focal and disseminated destructive lesions. (author)

  6. Combination radiotherapy in an orthotopic mouse brain tumor model.

    Science.gov (United States)

    Kramp, Tamalee R; Camphausen, Kevin

    2012-03-06

    Glioblastoma multiforme (GBM) are the most common and aggressive adult primary brain tumors. In recent years there has been substantial progress in the understanding of the mechanics of tumor invasion, and direct intracerebral inoculation of tumor provides the opportunity of observing the invasive process in a physiologically appropriate environment. As far as human brain tumors are concerned, the orthotopic models currently available are established either by stereotaxic injection of cell suspensions or implantation of a solid piece of tumor through a complicated craniotomy procedure. In our technique we harvest cells from tissue culture to create a cell suspension used to implant directly into the brain. The duration of the surgery is approximately 30 minutes, and as the mouse needs to be in a constant surgical plane, an injectable anesthetic is used. The mouse is placed in a stereotaxic jig made by Stoetling (figure 1). After the surgical area is cleaned and prepared, an incision is made; and the bregma is located to determine the location of the craniotomy. The location of the craniotomy is 2 mm to the right and 1 mm rostral to the bregma. The depth is 3 mm from the surface of the skull, and cells are injected at a rate of 2 μl every 2 minutes. The skin is sutured with 5-0 PDS, and the mouse is allowed to wake up on a heating pad. From our experience, depending on the cell line, treatment can take place from 7-10 days after surgery. Drug delivery is dependent on the drug composition. For radiation treatment the mice are anesthetized, and put into a custom made jig. Lead covers the mouse's body and exposes only the brain of the mouse. The study of tumorigenesis and the evaluation of new therapies for GBM require accurate and reproducible brain tumor animal models. Thus we use this orthotopic brain model to study the interaction of the microenvironment of the brain and the tumor, to test the effectiveness of different therapeutic agents with and without

  7. New prognostic model for extranodal natural killer/T cell lymphoma, nasal type.

    Science.gov (United States)

    Cai, Qingqing; Luo, Xiaolin; Zhang, Guanrong; Huang, Huiqiang; Huang, Hui; Lin, Tongyu; Jiang, Wenqi; Xia, Zhongjun; Young, Ken H

    2014-09-01

    Extranodal natural killer/T cell lymphoma, nasal type (ENKTL) is an aggressive disease with a poor prognosis, requiring risk stratification in affected patients. We designed a new prognostic model specifically for ENKTL to identify high-risk patients who need more aggressive therapy. We retrospectively reviewed 158 patients who were newly diagnosed with ENKTL. The estimated 5-year overall survival rate was 39.4 %. Independent prognostic factors included total protein (TP) 100 mg/dL, and Korean Prognostic Index (KPI) score ≥2. We constructed a new prognostic model by combining these prognostic factors: group 1 (64 cases (41.0 %)), no adverse factors; group 2 (58 cases (37.2 %)), one adverse factor; and group 3 (34 cases (21.8 %)), two or three adverse factors. The 5-year overall survival (OS) rates of these groups were 66.7, 23.0, and 5.9 %, respectively (p KPI model alone (p KPI model alone.

  8. [Sonographically detectable splenic disorders in dogs with malignant lymphoma].

    Science.gov (United States)

    Eberhardt, F; Köhler, C; Krastel, D; Winter, K; Alef, M; Kiefer, I

    2015-01-01

    To evaluate the frequency of different sonographic splenic disorders in dogs with different anatomic forms of malignant lymphoma. Additionally, the occurrence of the moth-eaten pattern in the parenchyma of the spleen in patients with diseases other than lymphoma should be investigated. Retrospective analysis of patient data collected from dogs histologically or cytologically diagnosed with malignant lymphoma and for which ultrasonographic images were available before the initiation of therapy. Patient data from dogs with a moth-eaten pattern within the splenic parenchyma were evaluated separately. Exclusion criterion was the administration of cytostatic agents prior to diagnosis. In 84% of 164 dogs with malignant lymphoma, an altered pattern of the spleen was diagnosed ultrasonographically. Ninety-four of these 137 patients had a moth-eaten pattern of the splenic parenchyma and 43 dogs displayed abnormalities in the form of splenomegaly, coarse echotexture or other changes of the parenchyma. When a moth-eaten pattern was diagnosed, the affected dogs suffered significantly more often from a multicentric lymphoma (95%) than from any other anatomical lymphoma form. Only one dog displayed a moth-eaten pattern of the splenic parenchyma without diagnosis of a malignant lymphoma. The positive predictive value of the moth-eaten pattern for malignant lymphoma was 99% and, in particular, for the multicentric lymphoma this was 95%. In total, 84% of the 164 dogs displayed a multicentric lymphoma, 5% a mediastinal or a cutaneous lymphoma, respectively, 4% a gastrointestinal lymphoma, and one animal had an ocular or renal lymphoma, respectively. Sonographic changes of the spleen are often diagnosed in dogs with malignant lymphoma, independent of the anatomical lymphoma form. When the moth-eaten pattern is observed, it is very likely that the affected dog suffers from a malignant lymphoma, most probably a multicentric lymphoma.

  9. Oncogene activation and surface markers in mouse lymphomas induced by radiation and nitrosomethylurea

    Energy Technology Data Exchange (ETDEWEB)

    Guerrero, I.; Villasante, A.; Diamond, L.; Berman, J.W.; Newcomb, E.W.; Steinberg, J.J.; Lake, R.; Pellicer, A.

    1986-01-01

    Thymic lymphomas have been induced by ..gamma..-radiation and treatment with the chemical nitrosomethylurea in different mice strains. As indicated by the NIH 3T3 focus forming assay, a significant percentage of the tumors contain activated oncogenes of the ras family (K or N). Cloning and sequencing has enabled us to identify single base mutations as the only significant alteration present in the activated oncogenes. These alterations result in the substitution of amino-acid 12 or 61 of the p21 product of the ras genes. With the use of synthetic oligonucleotides it has been found that the tumors do not all contain the same mutation and in one case so far the normal allele is absent.

  10. Iodine I 131 Monoclonal Antibody BC8 Before Autologous Stem Cell Transplant in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma or Non-Hodgkin Lymphoma

    Science.gov (United States)

    2017-11-15

    Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Hodgkin Lymphoma; Recurrent T-Cell Non-Hodgkin Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Hodgkin Lymphoma; Refractory T-Cell Non-Hodgkin Lymphoma

  11. The radiographic findings in diagnosis of pulmonary lymphoma

    International Nuclear Information System (INIS)

    Song Wei; Wang Li; Yan Hongzhen

    2001-01-01

    Objective: To study the radiographic findings in the diagnosis of pulmonary lymphoma and pseudo lymphoma. Methods: Eight patients with pulmonary lymphoma and 2 with pseudo lymphoma were examined by X-ray film, tomography, and CT. Results: Single or multiple nodules or masses were observed in 8 patients with pulmonary lymphoma, shaggy borders or halo of ground-glass attenuation in 7 patients, 2 patients had multiple patchy infiltrates bilaterally, 2 had diffuse interstitial infiltrates and 1 had miliary nodules. Multiple consolidations with air bronchogram and without hilar and mediastinal lymphadenopathy were observed in 2 patients with pulmonary pseudo lymphoma. Conclusion: Radiographic findings of pulmonary lymphoma were varied, the most common findings were the nodules or masses with shaggy borders or halo of ground-glass attenuation. The specific findings of pulmonary pseudo lymphoma were multiple consolidations with air bronchogram and without hilar and mediastinal lymphadenopathy. The final diagnosis relied on pathology

  12. Immunocompromised and immunocompetent mouse models for head and neck squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Lei ZG

    2016-01-01

    Full Text Available Zhen-ge Lei,1,* Xiao-hua Ren,2,* Sha-sha Wang,3 Xin-hua Liang,3,4 Ya-ling Tang3,5 1Department of Oral and Maxillofacial Surgery, Stomatological Hospital Affiliated to Nanchang University, Nanchang, Jiangxi, 2Department of Stomatology, Sichuan Medical Science Academy and Sichuan Provincial People’s Hospital, 3State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, 4Department of Oral and Maxillofacial Surgery, West China College of Stomatology, Sichuan University, 5Department of Oral Pathology, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, People’s Republic of China *These authors contributed equally to this work Abstract: Mouse models can closely mimic human oral squamous epithelial carcinogenesis, greatly expand the in vivo research possibilities, and play a critical role in the development of diagnosis, monitoring, and treatment of head and neck squamous cell carcinoma. With the development of the recent research on the contribution of immunity/inflammation to cancer initiation and progression, mouse models have been divided into two categories, namely, immunocompromised and immunocompetent mouse models. And thus, this paper will review these two kinds of models applied in head and neck squamous cell carcinoma to provide a platform to understand the complicated histological, molecular, and genetic changes of oral squamous epithelial tumorigenesis. Keywords: head and neck squamous cell carcinoma, HNSCC, mouse models, immunocompromised models, immunocompetent models, transgenic models

  13. Cutaneous double-hit B-cell lymphoma: an aggressive form of B-cell lymphoma with a propensity for cutaneous dissemination.

    Science.gov (United States)

    Magro, Cynthia M; Wang, Xuan; Subramaniyam, Shivakumar; Darras, Natasha; Mathew, Susan

    2014-04-01

    Diffuse large cell B-cell lymphoma of the skin is most commonly represented by diffuse large cell variants of primary cutaneous follicle center cell lymphoma and the leg-type lymphoma. In a minority of cases, the infiltrates are an expression of stage 4 disease of established extracutaneous B-cell lymphoma. We describe 3 patients with an aggressive form of B-cell lymphoma secondarily involving the skin. Two of the patients were in the ninth decade of life, whereas 1 patient was 34 years of age. In the elderly patients, there was an antecedent and/or concurrent history of follicular lymphoma, whereas in the younger patient, the tumor was a de novo presentation of this aggressive form of lymphoma. The elderly patients succumbed to their disease within less than a year from the time of diagnosis, whereas 1 patient is alive but with persistent and progressive disease despite chemotherapeutic intervention. The infiltrates in all 3 cases were diffuse and composed of large malignant hematopoietic cells that exhibited a round nucleus with a finely dispersed chromatin. Phenotypically, the tumor cells were Bcl-2 and CD10 positive, whereas Bcl-6 and Mum-1 showed variable positivity. One case showed combined Mum-1 positivity along with an acute lymphoblastic lymphoma phenotype, including the absence of CD20 expression. In each case, there was a c-MYC and BCL2/IGH rearrangement diagnostic of double-hit lymphoma. In one case, there was an additional BCL6 rearrangement, defining what is in essence triple-hit lymphoma. In conclusion, double-hit lymphoma is an aggressive form of B-cell neoplasia resistant to standard chemotherapy regimens, which in many but not all cases represents tumor progression in the setting of a lower grade B-cell malignancy.

  14. Precursor B lymphoblastic lymphoma of the orbit in a child: an unusual presentation of a non-Hodgkin lymphoma

    NARCIS (Netherlands)

    Faridpooya, K.; Mulder, M. M. S.; Merks, J. H. M.; de Smet, M. D.; Pals, S. T.; Saeed, P.

    2006-01-01

    OBJECTIVE: The majority of ocular adnexal lymphomas are marginal zone lymphomas, which occur rarely in children. This case report describes a 6 years old child with a precursor B lymphoblastic lymphoma presenting in the ocular adnexa. The combination of multi-agent chemotherapy with adjuvant

  15. Centralized mouse repositories.

    Science.gov (United States)

    Donahue, Leah Rae; Hrabe de Angelis, Martin; Hagn, Michael; Franklin, Craig; Lloyd, K C Kent; Magnuson, Terry; McKerlie, Colin; Nakagata, Naomi; Obata, Yuichi; Read, Stuart; Wurst, Wolfgang; Hörlein, Andreas; Davisson, Muriel T

    2012-10-01

    Because the mouse is used so widely for biomedical research and the number of mouse models being generated is increasing rapidly, centralized repositories are essential if the valuable mouse strains and models that have been developed are to be securely preserved and fully exploited. Ensuring the ongoing availability of these mouse strains preserves the investment made in creating and characterizing them and creates a global resource of enormous value. The establishment of centralized mouse repositories around the world for distributing and archiving these resources has provided critical access to and preservation of these strains. This article describes the common and specialized activities provided by major mouse repositories around the world.

  16. Methylation patterns in marginal zone lymphoma.

    Science.gov (United States)

    Arribas, Alberto J; Bertoni, Francesco

    Promoter DNA methylation is a major regulator of gene expression and transcription. The identification of methylation changes is important for understanding disease pathogenesis, for identifying prognostic markers and can drive novel therapeutic approaches. In this review we summarize the current knowledge regarding DNA methylation in MALT lymphoma, splenic marginal zone lymphoma, nodal marginal zone lymphoma. Despite important differences in the study design for different publications and the existence of a sole large and genome-wide methylation study for splenic marginal zone lymphoma, it is clear that DNA methylation plays an important role in marginal zone lymphomas, in which it contributes to the inactivation of tumor suppressors but also to the expression of genes sustaining tumor cell survival and proliferation. Existing preclinical data provide the rationale to target the methylation machinery in these disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. A Mouse Model for Human Anal Cancer

    Science.gov (United States)

    Stelzer, Marie K.; Pitot, Henry C.; Liem, Amy; Schweizer, Johannes; Mahoney, Charles; Lambert, Paul F.

    2010-01-01

    Human anal cancers are associated with high-risk human papillomaviruses (HPVs) that cause other anogenital cancers and head and neck cancers. As with other cancers, HPV16 is the most common high-risk HPV in anal cancers. We describe the generation and characterization of a mouse model for human anal cancer. This model makes use of K14E6 and K14E7 transgenic mice in which the HPV16 E6 and E7 genes are directed in their expression to stratified squamous epithelia. HPV16 E6 and E7 possess oncogenic properties including but not limited to their capacity to inactivate the cellular tumor suppressors p53 and pRb, respectively. Both E6 and E7 were found to be functionally expressed in the anal epithelia of K14E6/K14E7 transgenic mice. To assess the susceptibility of these mice to anal cancer, mice were treated topically with dimethylbenz[a]anthracene (DMBA), a chemical carcinogen that is known to induce squamous cell carcinomas in other sites. Nearly 50% of DMBA-treated HPV16 E6/E7 transgenic mice showed overt signs of tumors; whereas, none of the like treated non-transgenic mice showed tumors. Histopathological analyses confirmed that the HPV16 transgenic mice were increased in their susceptibility to anal cancers and precancerous lesions. Biomarker analyses demonstrated that these mouse anal cancers exhibit properties that are similar to those observed in HPV-positive precursors to human anal cancer. This is the first mouse model for investigating the contributions of viral and cellular factors in anal carcinogenesis, and should provide a platform for assessing new therapeutic modalities for treating and/or preventing this type of cancer. PMID:20947489

  18. Follicular lymphoma of the ocular adnexal region

    DEFF Research Database (Denmark)

    Rasmussen, Peter Kristian; Ralfkiaer, E.; Prause, J.U.

    2015-01-01

    Purpose To characterize the clinicopathological features of follicular lymphoma of the ocular adnexal region. Methods Retrospective nation-based study of Danish patients with ocular adnexal follicular lymphoma from January 1st 1980 through December 31st 2009. Results Twenty-four patients...... with ocular adnexal follicular lymphoma were identified. Fourteen (58%) of the patients were females. The median age was 63 years (range: 42–96 years). Eleven (46%) of the patients had primary ocular adnexal lymphoma, seven (29%) had an ocular adnexal lesion in conjunction with a concurrent systemic lymphoma...... and six patients (25%) presented with an ocular adnexal relapse. The most frequently affected sites were the lacrimal gland (38%) and the orbit (33%). Thirteen patients (54%) presented with Ann Arbor stage IE lymphoma, four (17%) had stage IIE, two patients (8%) stage IIIE, and five patients (21%) had...

  19. Stages of Adult Hodgkin Lymphoma

    Science.gov (United States)

    ... Lymphocyte-rich classical Hodgkin lymphoma. Age, gender, and Epstein-Barr infection can affect the risk of adult Hodgkin lymphoma. Anything that increases your risk of getting a disease is called a risk factor . Having a risk ...

  20. A consensus definition of cataplexy in mouse models of narcolepsy.

    Science.gov (United States)

    Scammell, Thomas E; Willie, Jon T; Guilleminault, Christian; Siegel, Jerome M

    2009-01-01

    People with narcolepsy often have episodes of cataplexy, brief periods of muscle weakness triggered by strong emotions. Many researchers are now studying mouse models of narcolepsy, but definitions of cataplexy-like behavior in mice differ across labs. To establish a common language, the International Working Group on Rodent Models of Narcolepsy reviewed the literature on cataplexy in people with narcolepsy and in dog and mouse models of narcolepsy and then developed a consensus definition of murine cataplexy. The group concluded that murine cataplexy is an abrupt episode of nuchal atonia lasting at least 10 seconds. In addition, theta activity dominates the EEG during the episode, and video recordings document immobility. To distinguish a cataplexy episode from REM sleep after a brief awakening, at least 40 seconds of wakefulness must precede the episode. Bouts of cataplexy fitting this definition are common in mice with disrupted orexin/hypocretin signaling, but these events almost never occur in wild type mice. It remains unclear whether murine cataplexy is triggered by strong emotions or whether mice remain conscious during the episodes as in people with narcolepsy. This working definition provides helpful insights into murine cataplexy and should allow objective and accurate comparisons of cataplexy in future studies using mouse models of narcolepsy.

  1. Stages of Childhood Hodgkin Lymphoma

    Science.gov (United States)

    ... Version Key Points Childhood Hodgkin lymphoma is a disease in which malignant (cancer) cells form in the lymph system. There are two types of childhood Hodgkin lymphoma. Epstein-Barr virus infection increases the risk of childhood Hodgkin ...

  2. Development and function of human innate immune cells in a humanized mouse model.

    Science.gov (United States)

    Rongvaux, Anthony; Willinger, Tim; Martinek, Jan; Strowig, Till; Gearty, Sofia V; Teichmann, Lino L; Saito, Yasuyuki; Marches, Florentina; Halene, Stephanie; Palucka, A Karolina; Manz, Markus G; Flavell, Richard A

    2014-04-01

    Mice repopulated with human hematopoietic cells are a powerful tool for the study of human hematopoiesis and immune function in vivo. However, existing humanized mouse models cannot support development of human innate immune cells, including myeloid cells and natural killer (NK) cells. Here we describe two mouse strains called MITRG and MISTRG, in which human versions of four genes encoding cytokines important for innate immune cell development are knocked into their respective mouse loci. The human cytokines support the development and function of monocytes, macrophages and NK cells derived from human fetal liver or adult CD34(+) progenitor cells injected into the mice. Human macrophages infiltrated a human tumor xenograft in MITRG and MISTRG mice in a manner resembling that observed in tumors obtained from human patients. This humanized mouse model may be used to model the human immune system in scenarios of health and pathology, and may enable evaluation of therapeutic candidates in an in vivo setting relevant to human physiology.

  3. Primary periosteal lymphoma: an unusual presentation of non-Hodgkin's lymphoma with radiographic, MR imaging, and pathologic correlation

    Energy Technology Data Exchange (ETDEWEB)

    Campbell, Scot E.; Beall, Douglas P.; Sanders, Timothy G. [Department of Radiology, Wilford Hall Medical Center, 759th MDTS/MTRD, 2200 Bergquist Drive, Suite 1, Lackland AFB, TX 78236-5300 (United States); Filzen, Timothy W.; Parsons, Theodore W. [Department of Orthopedic Surgery, Wilford Hall Medical Center, 59th MDW/MCSO, 2200 Bergquist Drive, Suite 1, Lackland AFB, TX 78236-5300 (United States); Bezzant, Shane M. [Department of Radiology, Brooke Army Medical Center, 3851 Roger Brooke Drive, Bldg 3600, Fort Sam Houston, TX 78234-6200 (United States); Burton, Mark P. [Department of Pathology, Wilford Hall Medical Center, 59th MDW/MTLP, 2200 Bergquist Drive, Suite 1, Lackland AFB, TX 78236-5300 (United States)

    2003-04-01

    This report describes a primary periosteal location of non-Hodgkin's lymphoma, without nodal disease, and without adjacent intramedullary disease at presentation. The clinical and imaging appearance of periosteal lymphoma simulates other neoplastic osseous surface tumors more than that of lymphoma in other locations. Consideration of this rare presentation of non-Hodgkin's lymphoma in the differential diagnosis of periosteal bone lesions can be helpful to ensure proper diagnosis and treatment. (orig.)

  4. Mantle cell lymphoma of the larynx: Primary case report

    Directory of Open Access Journals (Sweden)

    Naciri Sarah

    2012-07-01

    Full Text Available Abstract Introduction Primary laryngeal lymphomas are exceedingly rare. Only about a hundred cases have been reported. They consist mainly of non-Hodgkin lymphoma, especially of diffuse large B-cell lymphoma and mucosa-associated lymphoid tissue. We report the first case of a primary laryngeal mantle cell lymphoma. Case presentation We report a case of a primary mantle cell lymphoma of the larynx in a 70-year-old North African non-smoker male. We present a detailed report of his clinical and paraclinical data as well as treatment options. Conclusions Mantle cell lymphoma is a very aggressive lymphoma subset associated with poor prognosis. Laryngeal mantle cell lymphoma is exceedingly rare. To the best of our knowledge, this is the first case to ever be reported.

  5. Primary Hepatosplenic Large B-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    M.R. Morales-Polanco

    2008-03-01

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

  6. Development of a transgenic mouse model to study the immunogenicity of recombinant human insulin

    NARCIS (Netherlands)

    Torosantucci, Riccardo; Brinks, Vera; Kijanka, Grzegorz; Halim, Liem Andhyk; Sauerborn, Melody; Schellekens, Huub; Jiskoot, Wim

    2014-01-01

    Mouse models are commonly used to assess the immunogenicity of therapeutic proteins and to investigate the immunological processes leading to antidrug antibodies. The aim of this work was to develop a transgenic (TG) Balb/c mouse model for evaluating the immunogenicity of recombinant human insulin

  7. Evaluation of synthetic vascular grafts in a mouse carotid grafting model.

    Science.gov (United States)

    Chan, Alex H P; Tan, Richard P; Michael, Praveesuda L; Lee, Bob S L; Vanags, Laura Z; Ng, Martin K C; Bursill, Christina A; Wise, Steven G

    2017-01-01

    Current animal models for the evaluation of synthetic grafts are lacking many of the molecular tools and transgenic studies available to other branches of biology. A mouse model of vascular grafting would allow for the study of molecular mechanisms of graft failure, including in the context of clinically relevant disease states. In this study, we comprehensively characterise a sutureless grafting model which facilitates the evaluation of synthetic grafts in the mouse carotid artery. Using conduits electrospun from polycaprolactone (PCL) we show the gradual development of a significant neointima within 28 days, found to be greatest at the anastomoses. Histological analysis showed temporal increases in smooth muscle cell and collagen content within the neointima, demonstrating its maturation. Endothelialisation of the PCL grafts, assessed by scanning electron microscopy (SEM) analysis and CD31 staining, was near complete within 28 days, together replicating two critical aspects of graft performance. To further demonstrate the potential of this mouse model, we used longitudinal non-invasive tracking of bone-marrow mononuclear cells from a transgenic mouse strain with a dual reporter construct encoding both luciferase and green fluorescent protein (GFP). This enabled characterisation of mononuclear cell homing and engraftment to PCL using bioluminescence imaging and histological staining over time (7, 14 and 28 days). We observed peak luminescence at 7 days post-graft implantation that persisted until sacrifice at 28 days. Collectively, we have established and characterised a high-throughput model of grafting that allows for the evaluation of key clinical drivers of graft performance.

  8. Evaluation of synthetic vascular grafts in a mouse carotid grafting model.

    Directory of Open Access Journals (Sweden)

    Alex H P Chan

    Full Text Available Current animal models for the evaluation of synthetic grafts are lacking many of the molecular tools and transgenic studies available to other branches of biology. A mouse model of vascular grafting would allow for the study of molecular mechanisms of graft failure, including in the context of clinically relevant disease states. In this study, we comprehensively characterise a sutureless grafting model which facilitates the evaluation of synthetic grafts in the mouse carotid artery. Using conduits electrospun from polycaprolactone (PCL we show the gradual development of a significant neointima within 28 days, found to be greatest at the anastomoses. Histological analysis showed temporal increases in smooth muscle cell and collagen content within the neointima, demonstrating its maturation. Endothelialisation of the PCL grafts, assessed by scanning electron microscopy (SEM analysis and CD31 staining, was near complete within 28 days, together replicating two critical aspects of graft performance. To further demonstrate the potential of this mouse model, we used longitudinal non-invasive tracking of bone-marrow mononuclear cells from a transgenic mouse strain with a dual reporter construct encoding both luciferase and green fluorescent protein (GFP. This enabled characterisation of mononuclear cell homing and engraftment to PCL using bioluminescence imaging and histological staining over time (7, 14 and 28 days. We observed peak luminescence at 7 days post-graft implantation that persisted until sacrifice at 28 days. Collectively, we have established and characterised a high-throughput model of grafting that allows for the evaluation of key clinical drivers of graft performance.

  9. Primary malignant intramedullary lymphoma

    International Nuclear Information System (INIS)

    Orrego P, E.; Heinicke Y, H.; Arbaiza A, D.; Yepez R, V.

    1999-01-01

    A case of primary malignant intramedullary lymphoma, localized in the dorsal part of the spinal cord is presented. The clinical symptoms were associated with motor and sensitive deficit. Clinical investigations excluded the presence of lymphoma in other locations in the central nervous system and the extra neural organs. Postoperative radiotherapy and chemotherapy improved relict neurological symptoms. (authors)

  10. Among B cell non-Hodgkin's lymphomas, MALT lymphomas express a unique antibody repertoire with frequent rheumatoid factor reactivity

    NARCIS (Netherlands)

    Bende, Richard J.; Aarts, Wilhelmina M.; Riedl, Robert G.; de Jong, Daphne; Pals, Steven T.; van Noesel, Carel J. M.

    2005-01-01

    We analyzed the structure of antigen receptors of a comprehensive panel of mature B nonHodgkin's lymphomas (B-NHLs) by comparing, at the amino acid level, their immunoglobulin (Ig)V-H-CDR3s with CDR3 sequences present in GenBank. Follicular lymphomas, diffuse large B cell lymphomas, Burkitt's

  11. Role of Stat in Skin Carcinogenesis: Insights Gained from Relevant Mouse Models

    International Nuclear Information System (INIS)

    Macias, E.; Rao, D.; DiGiovanni, J.; DiGiovanni, J.; DiGiovanni, J.

    2013-01-01

    Signal transducer and activator of transcription 3 (Stat) is a cytoplasmic protein that is activated in response to cytokines and growth factors and acts as a transcription factor. Stat plays critical roles in various biological activities including cell proliferation, migration, and survival. Studies using keratinocyte-specific Stat-deficient mice have revealed that Stat plays an important role in skin homeostasis including keratinocyte migration, wound healing, and hair follicle growth. Use of both constitutive and inducible keratinocyte-specific Stat-deficient mouse models has demonstrated that Stat is required for both the initiation and promotion stages of multistage skin carcinogenesis. Further studies using a transgenic mouse model with a gain of function mutant of Stat (Stat3C) expressed in the basal layer of the epidermis revealed a novel role for Stat in skin tumor progression. Studies using similar Stat-deficient and gain-of-function mouse models have indicated its similar roles in ultraviolet B (UVB) radiation-mediated skin carcinogenesis. This paper summarizes the use of these various mouse models for studying the role and underlying mechanisms for the function of Stat in skin carcinogenesis. Given its significant role throughout the skin carcinogenesis process, Stat is an attractive target for skin cancer prevention and treatment.

  12. Hodgkin's Lymphoma of the Breast

    African Journals Online (AJOL)

    TNHJOURNALPH

    RESULT. A tissue diagnosis of Hodgkin's lymphoma with typical ... It was the first cancer to be cured ... ultrasonography showed enlarged liver. The .... McMillan A, Horning S. Non-Hodgkins lymphoma of the Breast. Cancer. 2007;110:25-30. 5.

  13. High treatment efficacy by dual targeting of Burkitt's lymphoma xenografted mice with a {sup 177}Lu-based CD22-specific radioimmunoconjugate and rituximab

    Energy Technology Data Exchange (ETDEWEB)

    Weber, Tobias; Boetticher, Benedikt; Keller, Armin; Schlegelmilch, Anne; Jaeger, Dirk; Krauss, Juergen [Heidelberg University Hospital, Department of Medical Oncology, National Center for Tumor Diseases, Heidelberg (Germany); Mier, Walter; Kraemer, Susanne; Leotta, Karin [Heidelberg University Hospital, Department of Nuclear Medicine, Heidelberg (Germany); Sauter, Max; Haberkorn, Uwe [Heidelberg University Hospital, Department of Nuclear Medicine, Heidelberg (Germany); German Cancer Research Center (DKFZ), Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany); Grosse-Hovest, Ludger [University of Tuebingen, Department of Immunology, Tuebingen (Germany); Arndt, Michaela A.E. [Heidelberg University Hospital, Department of Medical Oncology, National Center for Tumor Diseases, Heidelberg (Germany); German Cancer Research Center (DKFZ), Immunotherapy Program, National Center for Tumor Diseases, Heidelberg (Germany)

    2016-03-15

    Dual-targeted therapy has been shown to be a promising treatment option in recurrent and/or refractory B-cell non-Hodgkin's lymphoma (B-NHL). We generated radioimmunoconjugates (RICs) comprising either a novel humanized anti-CD22 monoclonal antibody, huRFB4, or rituximab, and the low-energy β-emitter {sup 177}Lu. Both RICs were evaluated as single agents in a human Burkitt's lymphoma xenograft mouse model. To increase the therapeutic efficacy of the anti-CD22 RIC, combination therapy with unlabelled anti-CD20 rituximab was explored. The binding activity of CHX-A''-DTPA-conjugated antibodies to target cells was analysed by flow cytometry. To assess tumour targeting of {sup 177}Lu-labelled antibodies, in vivo biodistribution experiments were performed. For radioimmunotherapy (RIT) studies, non-obese diabetic recombination activating gene-1 (NOD-Rag1{sup null}) interleukin-2 receptor common gamma chain (IL2r γ {sup null}) null mice (NRG mice) were xenografted subcutaneously with Raji Burkitt's lymphoma cells. {sup 177}Lu-conjugated antibodies were administered at a single dose of 9.5 MBq per mouse. For dual-targeted therapy, rituximab was injected at weekly intervals (0.5 - 1.0 mg). Tumour accumulation of RICs was monitored by planar scintigraphy. Conjugation of CHX-A''-DTPA resulted in highly stable RICs with excellent antigen-binding properties. Biodistribution experiments revealed higher tumour uptake of the {sup 177}Lu-labelled anti-CD22 IgG than of {sup 177}Lu-labelled rituximab. Treatment with {sup 177}Lu-conjugated huRFB4 resulted in increased tumour growth inhibition and significantly longer survival than treatment with {sup 177}Lu-conjugated rituximab. The therapeutic efficacy of the anti-CD22 RIC could be markedly enhanced by combination with unlabelled rituximab. These findings suggest that dual targeting with {sup 177}Lu-based CD22-specific RIT in combination with rituximab is a promising new treatment option for

  14. Mitochondrial-mediated apoptosis in lymphoma cells by the diterpenoid lactone Andrographolide, the active component of Andrographis paniculata

    Science.gov (United States)

    Yang, Shuo; Evens, Andrew M.; Prachand, Sheila; Singh, Amareshwar T.K; Bhalla, Savita; David, Kevin; Gordon, Leo I.

    2010-01-01

    Purpose Andrographolide is a diterpenoid lactone isolated from Andrographis paniculata (King of Bitters), an herbal medicine used in Asia. It has been reported to have anti-inflammatory, antihypertensive, anti-viral and immune-stimulant properties. Furthermore, it has been shown to inhibit cancer cell proliferation and induce apoptosis in leukemia and solid tumor cell lines. Experimental Design We studied the Burkitt p53 mutated Ramos cell line, the mantle-cell lymphoma (MCL) line Granta, the follicular lymphoma (FL) cell line HF-1 and the diffuse large B-cell lymphoma (DLBCL) cell line SUDHL4, as well as primary cells from patients with FL, DLBCL, and MCL. Results We found that andrographolide resulted in dose- and time-dependent cell death as measured by MTT. Andrographolide significantly increased reactive oxygen species (ROS) production in all cell lines. To determine mechanism of cell death, we measured apoptosis by Annexin-V/propidium iodide (PI) in the presence and absence of the antioxidant N-acetyl-L-cysteine (NAC), the glutathione-depleting agent buthionine sulfoxamine (BSO), or caspase inhibitors. We found that apoptosis was greatly enhanced by BSO, blocked by NAC, and accompanied by PARP cleavage and activation of caspases 3, 8 and 9. We measured BAX conformational change, and mitochondrial membrane potential, and using mouse embryonic fibroblast (MEF) Bax/Bak double knockouts (MEFBax−/−/Bak−/−), we found that apoptosis was mediated through mitochondrial pathways, but dependent on caspases in both cell lines and in patient samples. Conclusions Andrographolide caused ROS-dependent apoptosis in lymphoma cell lines and in primary tumor samples, which was enhanced by depletion of GSH and inhibited by NAC or the pan-caspase inhibitor Z-VAD-FMK. Further studies of diterpenoid lactones in lymphoma are warranted. PMID:20798229

  15. Appendiceal and ovarian Burkitt's lymphoma presenting as acute appendicitis

    Directory of Open Access Journals (Sweden)

    Donovan Hui

    2018-05-01

    Full Text Available Burkitt's lymphoma is an extremely aggressive B-cell non-Hodgkin lymphoma. Patients with the sporadic form of Burkitt's lymphoma typically present with a rapidly growing abdominal mass, pain and distension. Involvement of either the appendix and/or ovaries in females is a rare manifestation of the disease. We present an unusual case of a 13 year old girl with appendiceal and ovarian Burkitt's lymphoma presenting with signs of acute appendicitis. This case demonstrates the potential for secondary involvement of the appendix and/or ovaries from Burkitt's lymphoma as well as the importance of the histopathology. Keywords: Appendicitis, Appendix, Burkitt's lymphoma, Lymphoma, Ovarian tumor

  16. Clinical, immunophenotypic, and genetic analysis of adult lymphomas with morphologic features of Burkitt lymphoma

    NARCIS (Netherlands)

    Haralambieva, E; Boerma, EJ; van Imhoff, GW; Rosati, S; Schuuring, E; Muller-Hermelink, HK; Kluin, PM; Ott, G

    A prompt distinction of Burkitt lymphoma (BL) versus diffuse large B cell lymphomas (DLBCL) has important clinical implications; however, this distinction can be difficult. We analyzed 74 adult gray zone and 10 reference pediatric BL using immunohistochemistry (Ki-67, CD10, bcl2, bcl6) and

  17. A Rare Case of Composite Dural Extranodal Marginal Zone Lymphoma and Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

    Directory of Open Access Journals (Sweden)

    Mark Bustoros

    2018-04-01

    Full Text Available BackgroundPrimary extranodal marginal zone lymphoma (MZL of the dura is a rare neoplastic entity in the central nervous system (CNS.MethodsWe used literature searches to identify previously reported cases of primary dural MZL. We also reviewed clinical, pathologic, and radiographic data of an adult patient with concurrent dural MZL and chronic lymphocytic leukemia (CLL/small lymphocytic lymphoma (SLL.ResultsWe identified 104 cases of dural MZL in the literature. None of them presented concurrently with another type of non-Hodgkin lymphoma. This is the first report of composite lymphoma consisting of dural MZL and CLL/SLL in the bone marrow and lymph nodes.ConclusionPrimary dural MZL is a rare, indolent low-grade CNS lymphoma, with a relatively good prognosis. Its treatment is multidisciplinary and often requires surgical intervention due to brain compression, along with low to moderate doses of radiotherapy and/or systemic chemotherapy.

  18. Prognostic Assessment in Patients with Indolent B-Cell Lymphomas

    Directory of Open Access Journals (Sweden)

    Luca Arcaini

    2012-01-01

    Full Text Available Follicular lymphoma (FL is an indolent lymphoma with long median survival. Many studies have been performed to build up prognostic scores potentially useful to identify patients with poorer outcome. In 2004, an international consortium coordinated by the International Follicular Lymphoma Prognostic Factor project was established and a new prognostic study was launched (FLIPI2 using progression-free survival (PFS as main endpoint and integrating all the modern parameters prospectively collected. Low-grade non-Hodgkin lymphomas were once considered as a heterogenous group of lymphomas characterized by an indolent clinical course. Each entity is characterized by unique clinicobiologic features. Some studies have been focused on prognostic factors in single lymphoma subtypes, with the development of specific-entity scores based on retrospective series, for instance splenic marginal zone lymphoma (SMZL. A widely accepted prognostic tool for clinical usage for indolent non-follicular B-cell lymphomas is largely awaited. In this paper we summarized the current evidence regarding prognostic assessment of indolent follicular and non-follicular lymphomas.

  19. Lymphoma risk in systemic lupus

    DEFF Research Database (Denmark)

    Bernatsky, Sasha; Ramsey-Goldman, Rosalind; Joseph, Lawrence

    2014-01-01

    OBJECTIVE: To examine disease activity versus treatment as lymphoma risk factors in systemic lupus erythematosus (SLE). METHODS: We performed case-cohort analyses within a multisite SLE cohort. Cancers were ascertained by regional registry linkages. Adjusted HRs for lymphoma were generated...

  20. Tyrosine phosphorylation in human lymphomas

    NARCIS (Netherlands)

    Haralambieva, E; Jones, M.; Roncador, GM; Cerroni, L; Lamant, L; Ott, G; Rosenwald, A; Sherman, C; Thorner, P; Kusec, R; Wood, KM; Campo, E; Falini, B; Ramsay, A; Marafioti, T; Stein, H; Kluin, PM; Pulford, K; Mason, DY

    2002-01-01

    In a previous study, we showed that the high level of protein tyrosine phosphorylation present in lymphomas containing an anaplastic lymphoma kinase (ALK) can be demonstrated in routinely processed paraffin tissue sections using immunolabelling techniques. In the present study we investigated

  1. Dantrolene is neuroprotective in Huntington's disease transgenic mouse model

    Directory of Open Access Journals (Sweden)

    Chen Xi

    2011-11-01

    Full Text Available Abstract Background Huntington's disease (HD is a progressive neurodegenerative disorder caused by a polyglutamine expansion in the Huntingtin protein which results in the selective degeneration of striatal medium spiny neurons (MSNs. Our group has previously demonstrated that calcium (Ca2+ signaling is abnormal in MSNs from the yeast artificial chromosome transgenic mouse model of HD (YAC128. Moreover, we demonstrated that deranged intracellular Ca2+ signaling sensitizes YAC128 MSNs to glutamate-induced excitotoxicity when compared to wild type (WT MSNs. In previous studies we also observed abnormal neuronal Ca2+ signaling in neurons from spinocerebellar ataxia 2 (SCA2 and spinocerebellar ataxia 3 (SCA3 mouse models and demonstrated that treatment with dantrolene, a ryanodine receptor antagonist and clinically relevant Ca2+ signaling stabilizer, was neuroprotective in experiments with these mouse models. The aim of the current study was to evaluate potential beneficial effects of dantrolene in experiments with YAC128 HD mouse model. Results The application of caffeine and glutamate resulted in increased Ca2+ release from intracellular stores in YAC128 MSN cultures when compared to WT MSN cultures. Pre-treatment with dantrolene protected YAC128 MSNs from glutamate excitotoxicty, with an effective concentration of 100 nM and above. Feeding dantrolene (5 mg/kg twice a week to YAC128 mice between 2 months and 11.5 months of age resulted in significantly improved performance in the beam-walking and gait-walking assays. Neuropathological analysis revealed that long-term dantrolene feeding to YAC128 mice significantly reduced the loss of NeuN-positive striatal neurons and reduced formation of Httexp nuclear aggregates. Conclusions Our results support the hypothesis that deranged Ca2+ signaling plays an important role in HD pathology. Our data also implicate the RyanRs as a potential therapeutic target for the treatment of HD and demonstrate that Ryan

  2. Dantrolene is neuroprotective in Huntington's disease transgenic mouse model.

    Science.gov (United States)

    Chen, Xi; Wu, Jun; Lvovskaya, Svetlana; Herndon, Emily; Supnet, Charlene; Bezprozvanny, Ilya

    2011-11-25

    Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a polyglutamine expansion in the Huntingtin protein which results in the selective degeneration of striatal medium spiny neurons (MSNs). Our group has previously demonstrated that calcium (Ca2+) signaling is abnormal in MSNs from the yeast artificial chromosome transgenic mouse model of HD (YAC128). Moreover, we demonstrated that deranged intracellular Ca2+ signaling sensitizes YAC128 MSNs to glutamate-induced excitotoxicity when compared to wild type (WT) MSNs. In previous studies we also observed abnormal neuronal Ca2+ signaling in neurons from spinocerebellar ataxia 2 (SCA2) and spinocerebellar ataxia 3 (SCA3) mouse models and demonstrated that treatment with dantrolene, a ryanodine receptor antagonist and clinically relevant Ca2+ signaling stabilizer, was neuroprotective in experiments with these mouse models. The aim of the current study was to evaluate potential beneficial effects of dantrolene in experiments with YAC128 HD mouse model. The application of caffeine and glutamate resulted in increased Ca2+ release from intracellular stores in YAC128 MSN cultures when compared to WT MSN cultures. Pre-treatment with dantrolene protected YAC128 MSNs from glutamate excitotoxicty, with an effective concentration of 100 nM and above. Feeding dantrolene (5 mg/kg) twice a week to YAC128 mice between 2 months and 11.5 months of age resulted in significantly improved performance in the beam-walking and gait-walking assays. Neuropathological analysis revealed that long-term dantrolene feeding to YAC128 mice significantly reduced the loss of NeuN-positive striatal neurons and reduced formation of Httexp nuclear aggregates. Our results support the hypothesis that deranged Ca2+ signaling plays an important role in HD pathology. Our data also implicate the RyanRs as a potential therapeutic target for the treatment of HD and demonstrate that RyanR inhibitors and Ca2+ signaling stabilizers such as

  3. MYC/BCL2/BCL6 triple hit lymphoma: a study of 40 patients with a comparison to MYC/BCL2 and MYC/BCL6 double hit lymphomas.

    Science.gov (United States)

    Huang, Wenting; Medeiros, L Jeffrey; Lin, Pei; Wang, Wei; Tang, Guilin; Khoury, Joseph; Konoplev, Sergej; Yin, C Cameron; Xu, Jie; Oki, Yasuhiro; Li, Shaoying

    2018-05-21

    High-grade B-cell lymphomas with MYC, BCL2, and BCL6 rearrangements (triple hit lymphoma) are uncommon. We studied the clinicopathologic features of 40 patients with triple hit lymphoma and compared them to 157 patients with MYC/BCL2 double hit lymphoma and 13 patients with MYC/BCL6 double hit lymphoma. The triple hit lymphoma group included 25 men and 15 women with a median age of 61 years (range, 34-85). Nine patients had a history of B-cell lymphoma. Histologically, 23 (58%) cases were diffuse large B-cell lymphoma and 17 cases had features of B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma. Most cases of triple hit lymphoma were positive for CD10 (100%), BCL2 (95%), BCL6 (82%), MYC (74%), and 71% with MYC and BCL2 coexpression. P53 was overexpressed in 29% of triple hit lymphoma cases. The clinicopathological features of triple hit lymphoma patients were similar to patients with MYC/BCL2 and MYC/BCL6 double hit lymphoma, except that triple hit lymphoma cases were more often CD10 positive compared with MYC/BCL6 double hit lymphoma (p hit lymphoma and double hit lymphoma and overall survival in triple hit lymphoma patients was 17.6 months, similar to the overall survival of patients with double hit lymphoma (p = 0.67). Patients with triple hit lymphoma showing P53 overexpression had significantly worse overall survival compared with those without P53 overexpression (p = 0.04). On the other hand, double expressor status and prior history of B-cell lymphoma did not correlate with overall survival. In conclusion, most patients with triple hit lymphoma have an aggressive clinical course and poor prognosis and these tumors have a germinal center B-cell immunophenotype, similar to patients with double hit lymphomas. P53 expression is a poor prognostic factor in patients with triple hit lymphoma.

  4. Breed prevalence of canine lymphoma in South Africa

    Directory of Open Access Journals (Sweden)

    Liesl J. Van Rooyen

    2018-03-01

    Full Text Available Lymphoma is a common haematopoietic neoplasm in dogs. Several breeds have been shown to have a predisposition to lymphoma; however, very little information exists regarding the South African dog population. This study assessed whether any breed had increased odds of developing lymphoma compared with others, and also investigated the effects of age, sex and neutering status on disease prevalence. Two study populations and their corresponding reference populations were studied retrospectively. Odds ratios (ORs for lymphoma in 49 dog breeds, together with their 95% confidence intervals (CI, were calculated. Age effect was assessed by calculating ORs for different age categories in one of the populations. The chi-square test was used to evaluate differences in the prevalence of the various sex and neutering categories in one lymphoma population compared with its reference population. Fourteen breeds had significantly increased odds of developing lymphoma, and one breed had significantly decreased odds (p < 0.050. The median ages of the two lymphoma populations were 6.5 and 8.0 years, with the 6.1–9.0 year category having significantly increased odds of developing lymphoma (OR 1.61, CI 1.2–2.16, p = 0.002. In one of the lymphoma populations, higher proportions of males (p = 0.033 and neutered females (p = 0.006 were found when compared with the reference population. These findings suggest that certain breeds in South Africa have a higher risk of developing lymphoma, and that sex hormones may play a role in lymphoma pathogenesis. The findings may provide useful information for pet owners and veterinarians.

  5. Concomitant Classic Hodgkin Lymphoma of Lymph Node and cMYC-Positive Burkitt Leukemia/Lymphoma of the Bone Marrow Presented Concurrently at the Time of Presentation: A Rare Combination of Discordant Lymphomas

    Directory of Open Access Journals (Sweden)

    Dina S. Soliman

    2016-01-01

    Full Text Available Discordant lymphoma is rare condition in which different types of malignant lymphomas occurring in different anatomic sites. The two diseases may present clinically as concurrent or sequential disease (10. Herein we are reporting a Pakistani female in her 60s, a carrier of hepatitis B virus with multiple comorbidities presented with cervical lymphadenopathy, diagnosed as Hodgkin's lymphoma, mixed cellularity. During the staging workup, the patient was discovered to have extensive bone marrow (BM involvement by Burkitt leukaemia/lymphoma (BL. Cytogenetic analysis revealed positivity for t(8;14(q24;q32 confirmed by Fluorescence In Situ Hybridization (FISH for IGH/MYC. Epstein-Barr virus (EBV was demonstrated heavily in our case, with (EBV DNA of 24,295,560 copies/ml by PCR at time of presentation, in addition, the neoplastic cells in both diagnostic tissues (cervical lymph node and BM demonstrated positivity for EBV. A diagnosis of concomitant EBV related discordant lymphoma (classical Hodgkin lymphoma (cHL and Burkitt lymphoma (BL in leukemic phase was made. Among all reported cases, this case is highly exceptional because it is the first case of discordant/composite lymphoma, with this combination and concomitant presentation. Since we are dealing with a case with an exceptionally rare combination, we found it significant to elaborate more on its clinical features, contributing factors including EBV role, response to treatment, complications, and prognosis.

  6. 17-DMAG in Treating Patients With Metastatic or Unresectable Solid Tumors or Lymphomas

    Science.gov (United States)

    2013-01-24

    Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult T-cell Leukemia/Lymphoma; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome; Stage IV Small Lymphocytic Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific; Waldenstr

  7. J chain and myocyte enhancer factor 2B are useful in differentiating classical Hodgkin lymphoma from nodular lymphocyte predominant Hodgkin lymphoma and primary mediastinal large B-cell lymphoma.

    Science.gov (United States)

    Moore, Erika M; Swerdlow, Steven H; Gibson, Sarah E

    2017-10-01

    Although most classical Hodgkin lymphomas (CHLs) are easily distinguished from nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) and primary mediastinal large B-cell lymphoma (PMBL), cases with significant CD20 expression cause diagnostic confusion. Although the absence of OCT-2 and BOB.1 are useful in these circumstances, a variable proportion of CHLs are positive for these antigens. We investigated the utility of J chain and myocyte enhancer factor 2B (MEF2B) in the diagnosis of CHL; NLPHL; PMBL; T-cell/histiocyte-rich large B-cell lymphoma (TCRLBL); and B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and CHL, compared with OCT-2 and BOB.1. J chain and MEF2B highlighted lymphocyte predominant (LP) cells in 20/20 (100%) NLPHLs and were negative in 43/43 (100%) CHLs. Fourteen of 15 (93%) PMBLs and 4/4 (100%) TCRLBLs were MEF2B positive, whereas 67% of PMBLs and 50% of TCRLBLs were J chain positive. Three of 3 B-cell lymphomas, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and CHL, were negative for J chain and MEF2B. J chain and MEF2B were 100% sensitive and specific for NLPHL versus CHL. MEF2B was 100% sensitive and 98% specific for PMBL versus CHL. Whereas loss of OCT-2 and/or BOB.1 expression had a sensitivity of only 86% and specificity of 100% for CHL versus NLPHL, PMBL, and TCRLBL, lack of both J chain and MEF2B expression was 100% sensitive and 97% specific. J chain and MEF2B are highly sensitive and specific markers of NLPHL versus CHL; are particularly useful in highlighting LP cells; and, with rare exception, are of greater utility than OCT-2 and BOB.1 in differentiating CHL from NLPHL and other large B-cell lymphomas. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Pathology of nodal marginal zone lymphomas.

    Science.gov (United States)

    Pileri, Stefano; Ponzoni, Maurilio

    Nodal marginal zone B cell lymphomas (NMZLs) are a rare group of lymphoid disorders part of the spectrum of marginal zone B-cell lymphomas, which encompass splenic marginal one B-cell lymphoma (SMZL) and extra nodal marginal zone of B-cell lymphoma (EMZL), often of MALT-type. Two clinicopathological forms of NMZL are recognized: adult-type and pediatric-type, respectively. NMZLs show overlapping features with other types of MZ, but distinctive features as well. In this review, we will focus on the salient distinguishing features of NMZL mostly under morphological/immunophenotypical/molecular perspectives in views of the recent acquisitions and forthcoming updated 2016 WHO classification of lymphoid malignancies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Geldanamycin Analogue in Treating Patients With Advanced Solid Tumors or Non-Hodgkin's Lymphoma

    Science.gov (United States)

    2013-12-13

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Non-Hodgkin Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific

  10. Establishment of mouse neuron and microglial cell co-cultured models and its action mechanism.

    Science.gov (United States)

    Zhang, Bo; Yang, Yunfeng; Tang, Jun; Tao, Yihao; Jiang, Bing; Chen, Zhi; Feng, Hua; Yang, Liming; Zhu, Gang

    2017-06-27

    The objective of this study is to establish a co-culture model of mouse neurons and microglial cells, and to analyze the mechanism of action of oxygen glucose deprivation (OGD) and transient oxygen glucose deprivation (tOGD) preconditioning cell models. Mouse primary neurons and BV2 microglial cells were successfully cultured, and the OGD and tOGD models were also established. In the co-culture of mouse primary neurons and microglial cells, the cell number of tOGD mouse neurons and microglial cells was larger than the OGD cell number, observed by a microscope. CCK-8 assay result showed that at 1h after treatment, the OD value in the control group is lower compared to all the other three groups (P control group compared to other three groups (P neurons cells were cultured. In the meantime mouse BV2 microglia cells were cultured. Two types of cells were co-cultured, and OGD and tOGD cell models were established. There were four groups in the experiment: control group (OGD), treatment group (tOGD+OGD), placebo group (tOGD+OGD+saline) and minocycline intervention group (tOGD+OGD+minocycline). CCK-8 kit was used to detect cell viability and flow cytometry was used to detect apoptosis. In this study, mouse primary neurons and microglial cells were co-cultured. The OGD and tOGD models were established successfully. tOGD was able to effectively protect neurons and microglial cells from damage, and inhibit the apoptosis caused by oxygen glucose deprivation.

  11. Discrimination of lymphoma using laser-induced breakdown spectroscopy conducted on whole blood samples

    Science.gov (United States)

    Chen, Xue; Li, Xiaohui; Yang, Sibo; Yu, Xin; Liu, Aichun

    2018-01-01

    Lymphoma is a significant cancer that affects the human lymphatic and hematopoietic systems. In this work, discrimination of lymphoma using laser-induced breakdown spectroscopy (LIBS) conducted on whole blood samples is presented. The whole blood samples collected from lymphoma patients and healthy controls are deposited onto standard quantitative filter papers and ablated with a 1064 nm Q-switched Nd:YAG laser. 16 atomic and ionic emission lines of calcium (Ca), iron (Fe), magnesium (Mg), potassium (K) and sodium (Na) are selected to discriminate the cancer disease. Chemometric methods, including principal component analysis (PCA), linear discriminant analysis (LDA) classification, and k nearest neighbor (kNN) classification are used to build the discrimination models. Both LDA and kNN models have achieved very good discrimination performances for lymphoma, with an accuracy of over 99.7%, a sensitivity of over 0.996, and a specificity of over 0.997. These results demonstrate that the whole-blood-based LIBS technique in combination with chemometric methods can serve as a fast, less invasive, and accurate method for detection and discrimination of human malignancies. PMID:29541503

  12. A unique case of primary effusion lymphoma-like lymphoma showing disappearance and recurrence of the body cavity effusion.

    Science.gov (United States)

    Koeda, Chikahiko; Sato, Takashi; Matsumoto, Yuki; Usui, Yuta; Kunugida, Fusanori; Ogawa, Muneyoshi

    2017-03-01

    Primary effusion lymphoma-like lymphoma (PEL-LL) is a rare B-cell lymphoma that the etiology remains unclear. We describe a case of PEL-LL with a pleuropericardial effusion. Diagnosis required long period of time as it followed a unique progress of disappearance and recurrence of the body cavity effusion. We finally had a diagnosis of B-cell lymphoma by the immunocytochemistry of effusion using the cell block procedure. Authors consider that it is valuable to actively try the cell block procedure at the time of the first drainage for early diagnosis, if the body cavity effusion due to the malignancy is suspected.

  13. Intracerebral lymphoma with two patients. CT and MRI diagnosis

    International Nuclear Information System (INIS)

    Yanakiev, A.; Popovska, T.; Zasheva, I.

    2012-01-01

    Full text: Lymphoma (Hodgkin's and non-Hodgkin's) is a disease of the lymphatic system where the central neural system is affected in very rare cases. According to different authors the frequency of cases with lymphoma where the neural system is affected varies between 0.2% and 0.5%, and the primary cerebral lymphoma accounts for about 1-2% of all brain neoplasms. The intracranial form of lymphoma is usually a late onset of the disease with serious and potentially fatal complications for the patient. These complications usually appear several years after diagnosing the disease, but the cerebral lymphoma may occur even in patients who are in remission, which is actually the case with our patients. We present you two cases - a 38-year-old female and a 48-year-old male, who were hospitalized in Neuro ward with the following complaints: loss of speech for a few minutes, dizziness, weakness, tingling and shuffling of one of the legs. Those patients were diagnosed with histological B-cell non-Hodgkin's lymphoma and Hodgkin's lymphoma, several years ago. CT and MRI were carried out on the patients. Despite both clinical and radiographic suspicions for intracranial forms of lymphoma, the patients were still difficult to diagnose. A definitive diagnosis was given after a surgery and histological examination, i.e. non- Hodgkin's lymphoma - large B-cell lymphomas, and Hodgkin's lymphoma. These cases are of interest because of their rare intracranial localization of the lymphoma. The knowledge of CT and MRI images with the intracranial form of lymphoma may help diagnosing, but images should be interpreted together with the clinical and paraclinical results

  14. Lymphoma: Immune Evasion Strategies

    International Nuclear Information System (INIS)

    Upadhyay, Ranjan; Hammerich, Linda; Peng, Paul; Brown, Brian; Merad, Miriam; Brody, Joshua D.

    2015-01-01

    While the cellular origin of lymphoma is often characterized by chromosomal translocations and other genetic aberrations, its growth and development into a malignant neoplasm is highly dependent upon its ability to escape natural host defenses. Neoplastic cells interact with a variety of non-malignant cells in the tumor milieu to create an immunosuppressive microenvironment. The resulting functional impairment and dysregulation of tumor-associated immune cells not only allows for passive growth of the malignancy but may even provide active growth signals upon which the tumor subsequently becomes dependent. In the past decade, the success of immune checkpoint blockade and adoptive cell transfer for relapsed or refractory lymphomas has validated immunotherapy as a possible treatment cornerstone. Here, we review the mechanisms by which lymphomas have been found to evade and even reprogram the immune system, including alterations in surface molecules, recruitment of immunosuppressive subpopulations, and secretion of anti-inflammatory factors. A fundamental understanding of the immune evasion strategies utilized by lymphomas may lead to better prognostic markers and guide the development of targeted interventions that are both safer and more effective than current standards of care

  15. Lymphoma: Immune Evasion Strategies

    Energy Technology Data Exchange (ETDEWEB)

    Upadhyay, Ranjan; Hammerich, Linda; Peng, Paul [Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Brown, Brian [Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Merad, Miriam [Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Brody, Joshua D., E-mail: joshua.brody@mssm.edu [Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States)

    2015-04-30

    While the cellular origin of lymphoma is often characterized by chromosomal translocations and other genetic aberrations, its growth and development into a malignant neoplasm is highly dependent upon its ability to escape natural host defenses. Neoplastic cells interact with a variety of non-malignant cells in the tumor milieu to create an immunosuppressive microenvironment. The resulting functional impairment and dysregulation of tumor-associated immune cells not only allows for passive growth of the malignancy but may even provide active growth signals upon which the tumor subsequently becomes dependent. In the past decade, the success of immune checkpoint blockade and adoptive cell transfer for relapsed or refractory lymphomas has validated immunotherapy as a possible treatment cornerstone. Here, we review the mechanisms by which lymphomas have been found to evade and even reprogram the immune system, including alterations in surface molecules, recruitment of immunosuppressive subpopulations, and secretion of anti-inflammatory factors. A fundamental understanding of the immune evasion strategies utilized by lymphomas may lead to better prognostic markers and guide the development of targeted interventions that are both safer and more effective than current standards of care.

  16. Bovine lactoferricin induces caspase-independent apoptosis in human B-lymphoma cells and extends the survival of immune-deficient mice bearing B-lymphoma xenografts.

    Science.gov (United States)

    Furlong, Suzanne J; Mader, Jamie S; Hoskin, David W

    2010-06-01

    Although current treatments based on the use of B-cell-specific anti-CD20 monoclonal antibodies and aggressive combinatorial chemotherapy have improved the survival of patients suffering from B-cell non-Hodgkin's lymphoma (NHL), some individuals fail to respond to treatment and relapses remain common. New and more effective treatments for B-cell NHL are therefore required. Bovine lactoferricin (LfcinB) is a cationic antimicrobial peptide that is cytotoxic for several human tumor cell lines but does not harm healthy cells. Here we show that in vitro treatment with LfcinB caused Raji and Ramos human B-lymphoma cells to die by apoptosis, as indicated by DNA fragmentation, chromatin condensation, and nuclear disintegration. LfcinB killed B-lymphoma cells more efficiently at low serum concentrations and was inhibited in the presence of exogenous bovine serum albumin, suggesting partial neutralization of cationic LfcinB by anionic serum components. LfcinB-induced apoptosis in B-lymphoma cells was caspase-independent since caspase-3 activation was not detected by Western blotting and the general caspase inhibitor z-VAD-fmk did not prevent LfcinB-induced DNA fragmentation. Importantly, immune-deficient SCID/beige mice that were inoculated intravenously with Ramos B-lymphoma cells in order to model B-cell NHL exhibited extended survival following systemic administration of LfcinB, indicating that LfcinB warrants further investigation as a novel therapeutic agent for the possible treatment of B-cell NHL. Copyright 2010 Elsevier Inc. All rights reserved.

  17. Multilevel dysregulation of STAT3 activation in anaplastic lymphoma kinase-positive T/null-cell lymphoma

    DEFF Research Database (Denmark)

    Zhang, Qian; Raghunath, Puthryaveett N; Xue, Liquan

    2002-01-01

    Accumulating evidence indicates that expression of anaplastic lymphoma kinase (ALK), typically due to t(2;5) translocation, defines a distinct type of T/null-cell lymphoma (TCL). The resulting nucleophosmin (NPM) /ALK chimeric kinase is constitutively active and oncogenic. Downstream effector mol...

  18. Conditional Expression of Human 15-Lipoxygenase-1 in Mouse Prostate Induces Prostatic Intraepithelial Neoplasia: The FLiMP Mouse Model

    Directory of Open Access Journals (Sweden)

    Uddhav P. Kelavkar

    2006-06-01

    Full Text Available The incidence and mortality of prostate cancer (PCa vary greatly in different geographic regions, for which lifestyle factors, such as dietary fat intake, have been implicated. Human 15-lipoxygenase-1 (h15-LO-1, which metabolizes polyunsaturated fatty acids, is a highly regulated, tissue-specific, lipid-peroxidating enzyme that functions in physiological membrane remodeling and in the pathogenesis of atherosclerosis, inflammation, and carcinogenesis. We have shown that aberrant overexpression of 15-LO-1 occurs in human PCa, particularly high-grade PCa, and in high-grade prostatic intraepithelial neoplasia (HGPIN, and that the murine orthologue is increased in SV40-based genetically engineered mouse (GEM models of PCa, such as LADY and TRansgenic Adenocarcinoma of Mouse Prostate. To further define the role of 15-LO-1 in prostate carcinogenesis, we established a novel GEM model with targeted overexpression of h15-LO-1 in the prostate [human fifteen lipoxygenase-1 in mouse prostate (FLiMP]. We used a Cre- mediated and a loxP-mediated recombination strategy to target h15-LO-1 specifically to the prostate of C57BL/6 mice. Wild-type (wt, FLiMP+/-, and FLiMP+/+ mice aged 7 to 21, 24 to 28, and 35 weeks were characterized by histopathology, immunohistochemistry (IHC, and DNA/RNA and enzyme analyses. Compared to wt mice, h15-LO-1 enzyme activity was increased similarly in both homozygous FLiMP+/+ and hemizygous FLiMP+/- prostates. Dorsolateral and ventral prostates of FLiMP mice showed focal and progressive epithelial hyperplasia with nuclear atypia, indicative of the definition of mouse prostatic intraepithelial neoplasia (mPIN according to the National Cancer Institute. These foci showed increased proliferation by Ki-67 IHC. No progression to invasive PCa was noted up to 35 weeks. By IHC, h15-LO-1 expression was limited to luminal epithelial cells, with increased expression in mPIN foci (similar to human HGPIN. In summary, targeted overexpression of h

  19. Non-Hodgkin's lymphoma - the role of radiation therapy

    International Nuclear Information System (INIS)

    Gospodarowicz, Mary K.

    1995-01-01

    Objective: To review the approach to the diagnosis, assessment, treatment and continuing management of patients with Non-Hodgkin's lymphoma with the emphasis on the role of radiation therapy in this group of diseases. The entity of 'Non-Hodgkin's Lymphoma' encompasses a diverse group of disorders involving almost any part of the body. This diversity bedevils any attempt to unify the approach to this disease on a rational basis. Nevertheless, some broad principles can be applied to almost any presentation of Non-Hodgkin's lymphoma. The approach to the management of Non-Hodgkin's lymphoma is based on the histologic type, localization and extent of disease and other disease and patient related prognostic factors. The accurate pathologic diagnosis of lymphoma has been greatly facilitated by availability of markers, molecular and genetic techniques. The newly proposed revised classification of lymphomas and its impact on these of RT will be discussed. Although the Ann Arbor staging classification has been shown to provide important prognostic information, other factors have equivalent, if not greater, influence on outcome in patients with Non-Hodgkin's lymphomas. The management of lymphomas is based primarily on the histologic type and extent of the disease including stage, tumour bulk, number of sites involved and location of the disease. The success of curative radiation therapy is contingent upon the presence of localized disease, normal tissue tolerance allowing the delivery of RT curative dose (30-35 Gy) and the tumour bulk. The current evidence suggests that locoregional RT for stage I and II low grade lymphoma results in approximately 50% prolonged (10-15 years) failure free rate and possible cure. Radiation alone is no longer used for intermediate and high grade lymphomas. The standard management of stage I and II intermediate grade large cell and mixed lymphomas is with doxorubicin based chemotherapy (e.g. CHOP) followed by involved field radiation. The

  20. Gastric and colonic mantle cell lymphoma - incidental discovery.

    Science.gov (United States)

    Pitigoi, Dan; Stoica, Victor; Stoia, Razvan; Dobrea, Camelia; Becheanu, Gabriel; Diculescu, Mircea

    2009-03-01

    A 65-year old patient, with no medical history, was admitted for lower gastrointestinal bleeding. On clinical examination the patient seemed to be in good health. However the examination was completed with a rectosigmoidoscopy revealing the presence of mucosal erosions, ulcerations, multiple papulae. The histopathological examination raised the suspicion of a colonic lymphoma. Gastric biopsies suggested a gastric MALT type lymphoma associated to the colonic lymphoma, but the immunohistochemical profile corresponded to a mantle cell lymphoma. In spite of the general poor prognosis of mantle cell lymphoma, our patient had a good clinical and endoscopic response to the standard cyclophosphamide, vincristine, prednisone (CVP) therapy. The cases of gastric and colonic mantle lymphoma are rare, the response to therapy is poor; fortunately, our patient had a complete resolution after completion of the six cycles of chemotherapy.

  1. Mouse Models for Drug Discovery. Can New Tools and Technology Improve Translational Power?

    Science.gov (United States)

    Zuberi, Aamir; Lutz, Cathleen

    2016-01-01

    Abstract The use of mouse models in biomedical research and preclinical drug evaluation is on the rise. The advent of new molecular genome-altering technologies such as CRISPR/Cas9 allows for genetic mutations to be introduced into the germ line of a mouse faster and less expensively than previous methods. In addition, the rapid progress in the development and use of somatic transgenesis using viral vectors, as well as manipulations of gene expression with siRNAs and antisense oligonucleotides, allow for even greater exploration into genomics and systems biology. These technological advances come at a time when cost reductions in genome sequencing have led to the identification of pathogenic mutations in patient populations, providing unprecedented opportunities in the use of mice to model human disease. The ease of genetic engineering in mice also offers a potential paradigm shift in resource sharing and the speed by which models are made available in the public domain. Predictively, the knowledge alone that a model can be quickly remade will provide relief to resources encumbered by licensing and Material Transfer Agreements. For decades, mouse strains have provided an exquisite experimental tool to study the pathophysiology of the disease and assess therapeutic options in a genetically defined system. However, a major limitation of the mouse has been the limited genetic diversity associated with common laboratory mice. This has been overcome with the recent development of the Collaborative Cross and Diversity Outbred mice. These strains provide new tools capable of replicating genetic diversity to that approaching the diversity found in human populations. The Collaborative Cross and Diversity Outbred strains thus provide a means to observe and characterize toxicity or efficacy of new therapeutic drugs for a given population. The combination of traditional and contemporary mouse genome editing tools, along with the addition of genetic diversity in new modeling

  2. Mouse Models for Drug Discovery. Can New Tools and Technology Improve Translational Power?

    Science.gov (United States)

    Zuberi, Aamir; Lutz, Cathleen

    2016-12-01

    The use of mouse models in biomedical research and preclinical drug evaluation is on the rise. The advent of new molecular genome-altering technologies such as CRISPR/Cas9 allows for genetic mutations to be introduced into the germ line of a mouse faster and less expensively than previous methods. In addition, the rapid progress in the development and use of somatic transgenesis using viral vectors, as well as manipulations of gene expression with siRNAs and antisense oligonucleotides, allow for even greater exploration into genomics and systems biology. These technological advances come at a time when cost reductions in genome sequencing have led to the identification of pathogenic mutations in patient populations, providing unprecedented opportunities in the use of mice to model human disease. The ease of genetic engineering in mice also offers a potential paradigm shift in resource sharing and the speed by which models are made available in the public domain. Predictively, the knowledge alone that a model can be quickly remade will provide relief to resources encumbered by licensing and Material Transfer Agreements. For decades, mouse strains have provided an exquisite experimental tool to study the pathophysiology of the disease and assess therapeutic options in a genetically defined system. However, a major limitation of the mouse has been the limited genetic diversity associated with common laboratory mice. This has been overcome with the recent development of the Collaborative Cross and Diversity Outbred mice. These strains provide new tools capable of replicating genetic diversity to that approaching the diversity found in human populations. The Collaborative Cross and Diversity Outbred strains thus provide a means to observe and characterize toxicity or efficacy of new therapeutic drugs for a given population. The combination of traditional and contemporary mouse genome editing tools, along with the addition of genetic diversity in new modeling systems

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

    Science.gov (United States)

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

    2009-11-01

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

  4. Double-hit B-cell lymphomas

    NARCIS (Netherlands)

    Aukema, Sietse M.; Siebert, Reiner; Schuuring, Ed; van Imhoff, Gustaaf W.; Kluin-Nelemans, Hanneke C.; Boerma, Evert-Jan; Kluin, Philip M.

    2011-01-01

    In many B-cell lymphomas, chromosomal translocations are biologic and diagnostic hallmarks of disease. An intriguing subset is formed by the so-called double-hit (DH) lymphomas that are defined by a chromosomal breakpoint affecting the MYC/8q24 locus in combination with another recurrent breakpoint,

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

    Directory of Open Access Journals (Sweden)

    Luis Alberto de Pádua Covas Lage

    2015-08-01

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

  6. Natural History Study of Monoclonal B Cell Lymphocytosis (MBL), Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Lymphoplasmacytic Lymphoma (LPL)/Waldenstrom Macroglobulinemia (WM), and Splenic Marginal Zone Lymphoma (SMZL)

    Science.gov (United States)

    2018-05-10

    B-Cell Chronic Lymphocytic Leukemia; Monoclonal B-Cell Lymphocytosis; Lymhoma, Small Lymphocytic; Chronic Lymphocytic Leukemia; Lymphoplasmacytic Lymphoma; Waldenstrom Macroglobulinemia; Splenic Marginal Zone Lymphoma

  7. Clinical Significance of "Double-hit" and "Double-protein" expression in Primary Gastric B-cell Lymphomas.

    Science.gov (United States)

    He, Miaoxia; Chen, Keting; Li, Suhong; Zhang, Shimin; Zheng, Jianming; Hu, Xiaoxia; Gao, Lei; Chen, Jie; Song, Xianmin; Zhang, Weiping; Wang, Jianmin; Yang, Jianmin

    2016-01-01

    Primary gastric B-cell lymphoma is the second most common malignancy of the stomach. There are many controversial issues about its diagnosis, treatment and clinical management. "Double-hit" and "double-protein" involving gene rearrangement and protein expression of c-Myc and bcl2/bcl6 are the most used terms to describe DLBCL poor prognostic factors in recent years. However, very little is known about the role of these prognostic factors in primary gastric B-cell lymphomas. This study aims to obtain a molecular pathology prognostic model of gastric B-cell lymphoma for clinical stratified management by evaluating how the "double-hit" and "double-protein" in tumor cells as well as microenvironmental reaction of tumor stromal tissue affect clinical outcome in primary gastric B-cell lymphomas. Data and tissues of 188 cases diagnosed with gastric B-cell lymphomas were used in this study. Tumor tissue microarray (TMA) of formalin fixed and paraffin embedded (FFPE) tissues was constructed for fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) analysis with a serial of biomarkers containing MYC, BCL2, BCL6, CD31, SPARC, CD10, MUM1 and Ki-67. Modeled period analysis was used to estimate 3-year and 5-year overall survival (OS) and disease-free survival (DFS) distributions. There was no definite "double-hit" case though the gene rearrangement of c-Myc (5.9%), bcl2 (0.1%) and bcl6 (7.4%) was found in gastric B-cell lymphomas. The gene amplification or copy gains of c-Myc (10.1%), bcl-2 (17.0%) and bcl-6 (0.9%) were present in these lymphomas. There were 12 cases of the lymphomas with the "double-protein" expression of MYC and BCL2/BCL6. All patients with "double-protein" gastric B-cell lymphomas had poor outcome compared with those without. More importantly, "MYC-BCL2-BCL6" negative group of gastric B-cell lymphoma patients had favorable clinical outcome regardless clinical stage, pathological types and therapeutic modalities. And the similar better

  8. A preclinical mouse model of invasive lobular breast cancer metastasis

    NARCIS (Netherlands)

    Doornebal, Chris W.; Klarenbeek, Sjoerd; Braumuller, Tanya M.; Klijn, Christiaan N.; Ciampricotti, Metamia; Hau, Cheei-Sing; Hollmann, Markus W.; Jonkers, Jos; de Visser, Karin E.

    2013-01-01

    Metastatic disease accounts for more than 90% of cancer-related deaths, but the development of effective antimetastatic agents has been hampered by the paucity of clinically relevant preclinical models of human metastatic disease. Here, we report the development of a mouse model of spontaneous

  9. MALT LYMPHOMA OF PALATE AND ORBIT

    Directory of Open Access Journals (Sweden)

    VIVIANA ANDREA CIFUENTES NAVAS

    2018-05-01

    Full Text Available TITLE: Malt palate and orbit lymphoma  Authors: CIFUENTES NAVAS-Viviana Andrea; MARTÍN PASCUAL- María Consolación; FERNÁNDEZ RODRÍGUEZ- Ana; ALONSO MESONERO- Marta; CHAVIANO GRAHJERA-Juan; MORAIS PÉREZ-Darío. INTRODUCTIONMALT-type lymphomas are lymphoid proliferations originated in the glandular epithelium of organs like the stomach, the salivary and lacrimal glands, and even, we can find lymphoid neoformations of non-epithelial localization, like in the orbital soft tissue. The lymphomas of the mucosal-associated lymphatic tissue (MALT represent only 0.2-0.3% and constitute a well-defined group of non-Hodgkin lymphomas of B origin. In the field of oral pathology, the salivary glands, tonsils and palate are mainly affected, it is more rare to find it in jugal mucosa.We present a rare case of MALT lymphoma with involvement of the palate and orbit. MATERIAL AND METHODS84-year-old patient with multiple pathologies. Derived from his primary care physician due to pharyngeal complaints of 4 to 5 days of evolution, associated with a painful palate lesion.He presented in right hemipaladar a tumoration of elastic consistency in submucosa, ulcerated in the center, with normal neck. Also left orbital tumor that limits the visual field. RESULTSCT and MRI of the neck report mass of 4x4 x2.5 cm in right hemipaladar, noninfiltrating concordant with possible lymphoma. The orbital MRI describes an intra and extra nasal left nasal lesion of 2.3x1.2x2 cm with characteristics consistent with lymphoma. CT of the neck: It demostrates a great mass of right hemipaladar, with lobulated contours and homogeneous enhancement of 40x32x25 mm, in intimate contact with medial pterygoid muscle, although there were no signs of infiltration, the rest of the edges being well delimited. Images characteristics look like a lymphoma, without being able to rule out other etiologies. MRI of the neck: It demostrates a diffuse thickening of right side of the soft palate that

  10. DNA alkylating agents alleviate silencing of class II transactivator gene expression in L1210 lymphoma cells.

    Science.gov (United States)

    Murphy, Shawn P; Holtz, Renae; Lewandowski, Nicole; Tomasi, Thomas B; Fuji, Hiroshi

    2002-09-15

    MHC class II (Ia) Ag expression is inversely correlated with tumorigenicity and directly correlated with immunogenicity in clones of the mouse L1210 lymphoma (1 ). Understanding the mechanisms by which class II Ag expression is regulated in L1210 lymphoma may facilitate the development of immunotherapeutic approaches for the treatment of some types of lymphoma and leukemia. This study demonstrates that the variation in MHC class II Ag expression among clones of L1210 lymphoma is due to differences in the expression of the class II transactivator (CIITA). Analysis of stable hybrids suggests that CIITA expression is repressed by a dominant mechanism in class II-negative L1210 clones. DNA-alkylating agents such as ethyl methanesulfonate and the chemotherapeutic drug melphalan activate CIITA and class II expression in class II negative L1210 cells, and this effect appears to be restricted to transformed cell lines derived from the early stages of B cell ontogeny. Transient transfection assays demonstrated that the CIITA type III promoter is active in class II(-) L1210 cells, despite the fact that the endogenous gene is not expressed, which suggests that these cells have all of the transacting factors necessary for CIITA transcription. An inverse correlation between methylation of the CIITA transcriptional regulatory region and CIITA expression was observed among L1210 clones. Furthermore, 5-azacytidine treatment activated CIITA expression in class II-negative L1210 cells. Collectively, our results suggest that 1) CIITA gene expression is repressed in class II(-) L1210 cells by methylation of the CIITA upstream regulatory region, and 2) treatment with DNA-alkylating agents overcomes methylation-based silencing of the CIITA gene in L1210 cells.

  11. Biology and therapy of inherited retinal degenerative disease: insights from mouse models

    Science.gov (United States)

    Veleri, Shobi; Lazar, Csilla H.; Chang, Bo; Sieving, Paul A.; Banin, Eyal; Swaroop, Anand

    2015-01-01

    Retinal neurodegeneration associated with the dysfunction or death of photoreceptors is a major cause of incurable vision loss. Tremendous progress has been made over the last two decades in discovering genes and genetic defects that lead to retinal diseases. The primary focus has now shifted to uncovering disease mechanisms and designing treatment strategies, especially inspired by the successful application of gene therapy in some forms of congenital blindness in humans. Both spontaneous and laboratory-generated mouse mutants have been valuable for providing fundamental insights into normal retinal development and for deciphering disease pathology. Here, we provide a review of mouse models of human retinal degeneration, with a primary focus on diseases affecting photoreceptor function. We also describe models associated with retinal pigment epithelium dysfunction or synaptic abnormalities. Furthermore, we highlight the crucial role of mouse models in elucidating retinal and photoreceptor biology in health and disease, and in the assessment of novel therapeutic modalities, including gene- and stem-cell-based therapies, for retinal degenerative diseases. PMID:25650393

  12. Expression of CD56 and Epstein-Barr virus in nasal/nasopharyngeal lymphoma

    International Nuclear Information System (INIS)

    Lee, Seung Sook; Cho, Kyung Ja

    1997-12-01

    We examined malignant lymphomas and polymorphic reticulosis of nasal cavity, nasopharynx, and palate, diagnosed at Korea Cancer Center Hospital from 1987 to 1996. With immunophenotypic study, we reclassified nasal/nasopharyngeal lymphomas into three categories: CD56-positive T/NK lymphoma, CD56-negative lymphoma and B-cell lymphoma. Malignant lymphomas of nasal cavity, nasopharynx and palate were 95 patient, that comprised 11% of the total lymphoma cases, and it was the most common extranodal lymphoma. Twenty-five percent were B-cell lymphomas and 75 % were T/NK lymphomas. According to site, nasal cavity was the most frequent and 91 % of nasal cavity lymphomas were T/NK type. CD56-positive T/NK comprised 82 % of total T/NK lymphomas and CD56-negative cases were 18 %. In 89 % of total T/NK lymphomas, many tumor cells expressed EBER-1 in their nuclei (CD56+ T/NK lymphoma: 97 % of EBV expression, CD56-T-cell lymphoma; 60%). Only one case (5%) of B-cell lymphoma showed EBER-1 positivity in a few cells. CD56+ T/NK lymphomas showed significantly more angiocentricity and severe necrosis than CD56- cases. Although it has no statistical significance, T/NK lymphomas has a tendency to lower survival rates than B-cell lymphomas at 1 year and 2 year. CD56+ T/NK lymphomas has a tendency to lower survival than CD56- T/NK lymphomas (p > 0.05). Our results of this project will serve important basic materials in diagnosing and studying lymphoma. (author). 25 refs., 4 tabs., 4 figs

  13. Primary periosteal lymphoma - rare and unusual

    Energy Technology Data Exchange (ETDEWEB)

    Abdelwahab, Ibrahim F. [Coney Island Hospital, Department of Radiology, New York, NY (United States); Hoch, Benjamin [Mount Sinai School of Medicine, CUNY, Department of Pathology, New York, NY (United States); Hermann, George [Mount Sinai School of Medicine, CUNY, Department of Radiology, New York, NY (United States); Bianchi, Stefano [Clinique et Fondation des Grangettes, Geneva (Switzerland); Klein, Michael J. [UAB School of Medicine, Department of Pathology, Birmingham, AL (United States); Springfield, Dempsey S. [Mount Sinai School of Medicine, CUNY, Department of Orthopedics, New York, NY (United States)

    2007-04-15

    We describe a primary periosteal lymphoma that involved only the periosteum without affecting the adjacent medulla or the regional lymph nodes. No other lymphomatous foci were found in either the distant lymph nodes or viscera. This unusual presentation simulates the imaging appearance of surface lesions of bone, namely benign and malignant tumors, and departs from the typical appearance of primary lymphoma of bone. Therefore, this rare type of lymphoma should be considered in the differential diagnosis of surface bone lesions. (orig.)

  14. [Predictive value of Hodgkin's lymphoma tumor burden in present].

    Science.gov (United States)

    Kulyova, S A; Karitsky, A P

    2014-01-01

    Today approximately 70% of patients with Hodgkin lymphoma can be cured with the combined-modality therapy. Tumor burden, the importance of which was demonstrated 15 years ago for the first time, is a powerful prognostic factor. Data of literature of representations on predictive value of Hodgkin's lymphoma tumor burden are shown in the article. The difficult immunological relations between tumor cells and reactive ones lead to development of the main symptoms. Nevertheless, the collective sign of tumor burden shows the greatest influence on survival and on probability of resistance, which relative risk can be predicted on this variable and treatment program. Patients with bulky disease need escalated therapy with high-dose chemotherapy. Integration into predictive models of the variable will change an expected contribution of clinical and laboratory parameters in the regression analyses constructed on patients with Hodgkin's lymphoma. Today the role of diagnostic functional methods, in particular a positron emission tomography, for metabolic active measurement is conducted which allows excluding a reactive component.

  15. Transcranial magnetic stimulation of mouse brain using high-resolution anatomical models

    Science.gov (United States)

    Crowther, L. J.; Hadimani, R. L.; Kanthasamy, A. G.; Jiles, D. C.

    2014-05-01

    Transcranial magnetic stimulation (TMS) offers the possibility of non-invasive treatment of brain disorders in humans. Studies on animals can allow rapid progress of the research including exploring a variety of different treatment conditions. Numerical calculations using animal models are needed to help design suitable TMS coils for use in animal experiments, in particular, to estimate the electric field induced in animal brains. In this paper, we have implemented a high-resolution anatomical MRI-derived mouse model consisting of 50 tissue types to accurately calculate induced electric field in the mouse brain. Magnetic field measurements have been performed on the surface of the coil and compared with the calculations in order to validate the calculated magnetic and induced electric fields in the brain. Results show how the induced electric field is distributed in a mouse brain and allow investigation of how this could be improved for TMS studies using mice. The findings have important implications in further preclinical development of TMS for treatment of human diseases.

  16. Hypothalamic food intake regulation in a cancer-cachectic mouse model

    NARCIS (Netherlands)

    Dwarkasing, J.T.; Dijk, van M.; Dijk, F.J.; Boekschoten, M.V.; Faber, J.; Argiles, J.M.; Laviano, A.; Müller, M.R.; Witkamp, R.F.; Norren, van K.

    2014-01-01

    Background Appetite is frequently affected in cancer patients leading to anorexia and consequently insufficient food intake. In this study, we report on hypothalamic gene expression profile of a cancer-cachectic mouse model with increased food intake. In this model, mice bearing C26 tumour have an

  17. Treatment Options for Non-Hodgkin Lymphoma

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... lymphoma may come back as indolent lymphoma. Treatment Option Overview Key Points There are different types of ...

  18. Radiotherapy for the primary ocular adnexal lymphoma

    International Nuclear Information System (INIS)

    Yu Dahai; Sun Sanyuan; Zhuo Shichao; Wang Haiwei

    2007-01-01

    Objective: To study the pathological and clinical characteristics of primary lymphoma of ocular adnexae, analyze the treatment results and discuss the methods to prevent radiation complications. Methods: From Feb. 1995 to Feb. 2004, 25 patients with primary ocular adnexal lymphoma were treated in the second hospital and the forth hospital of Xuzhou, including 11 males and 14 females. The diagnosis was confirmed pathologically by biopsy in 19 patients and lumpectomy in 6 patients, including 22 mucosa-associated lymphoid tissue (MALT) lymphoma and 3 non-MALT lymphoma. According to the Ann Arbor Staging System, there were 21 patients with tumor in stage I E, 3 in stage II E and 1 in stage III E. The primary tumor was found in the eyelid or conjunctiva in 19 eyes and orbit in 9 eyes. Radiotherapy were given to 22 patients (25 eyes) by deep X-rays, 60 Co γ-rays or mixed beams. The total irradiation dose ranged from 30.0 to 57.6 Gy. Kaplan-Meier method was used to calculate the survival rate and Logrank test was used to detect the difference between the different groups. Results: The 5-, 10-year accumulated survival rates (SR) of the whole group were 90% and 82%. The 10-year SR of patients with primary, eyelid or conjunctiva tumor and orbit tumor were 100% and 58% (P=0.032). The local control rates of the radiotherapy group and non-radiotherapy group were 92% and 33 % (P=0.006). The 10-year SR of patients with tumor completely removed and those with residues were 83% and 82% (P=0.907). The 10-year SR of MALT lymphoma and non-MALT lymphoma were 90.0% and 33.3% (P=0.009). After radiotherapy, 8 eyes (36%) had cataract formation and 7 eyes (28%) had xerophalmic symptoms. Conclusions: The results of radiothera- py for the primary ocular adnexal lymphoma are satisactory. The prognosis of patients with primary, eyelid or conjunctiva tumor is better than those with orbit tumor. The vast majority of the primary ocular adnexal lymphomas are MALT lymphomas. The survival rate of

  19. FDG-PET in Follicular Lymphoma Management

    Directory of Open Access Journals (Sweden)

    C. Bodet-Milin

    2012-01-01

    Full Text Available 18-Fluoro-deoxyglucose positron emission tomography/computerised tomography (FDG PET/CT is commonly used in the management of patients with lymphomas and is recommended for both initial staging and response assessment after treatment in patients with diffuse large B-cell lymphoma and Hodgkin lymphoma. Despite the FDG avidity of follicular lymphoma (FL, FDG PET/CT is not yet applied in standard clinical practice for patients with FL. However, FDG PET/CT is more accurate than conventional imaging for initial staging, often prompting significant management change, and allows noninvasive characterization to guide assessment of high-grade transformation. For restaging, FDG PET/CT assists in distinguishing between scar tissue and viable tumors in residual masses and a positive PET after induction treatment would seem to predict a shorter progression-free survival.

  20. Modern radiation therapy for extranodal lymphomas

    DEFF Research Database (Denmark)

    Yahalom, Joachim; Illidge, Tim; Specht, Lena

    2015-01-01

    Extranodal lymphomas (ENLs) comprise about a third of all non-Hodgkin lymphomas (NHL). Radiation therapy (RT) is frequently used as either primary therapy (particularly for indolent ENL), consolidation after systemic therapy, salvage treatment, or palliation. The wide range of presentations of ENL...... and treatment planning for the most frequently involved organs. Specifically, detailed recommendations for RT volumes are provided. We have applied the same modern principles of involved site radiation therapy as previously developed and published as guidelines for Hodgkin lymphoma and nodal NHL. We have...... there is a lack of guidelines for the use of RT in the management of ENL. This report presents an effort by the International Lymphoma Radiation Oncology Group (ILROG) to harmonize and standardize the principles of treatment of ENL, and to address the technical challenges of simulation, volume definition...

  1. Primary non-Hodgkin′s lymphoma of the salivary gland: A spectrum of lymphoepithelial sialadenitis, low-grade B-cell lymphoma of mucosa-associated lymphoid tissue with transformation to high-grade lymphoma

    Directory of Open Access Journals (Sweden)

    Agale Shubhangi

    2010-04-01

    Full Text Available Lymphoid infiltrates of the salivary gland can be either reactive or neoplastic. The reactive lesion, lymphoepithelial sialadenitis (LESA may be associated with Sjogren′s syndrome (SS or may occur as an isolated salivary gland enlargement. Patients with LESA/SS have a particularly high risk of subsequently developing lymphoma, which is a low-grade mucosa-associated lymphoid tissue (MALT type lymphoma of the salivary gland. We document a rare case of primary non-Hodgkin′s lymphoma of the parotid gland arising in the background of LESA and with a rare example of transformation from low grade to high-grade B cell lymphoma of MALT type.

  2. Impaired spatial processing in a mouse model of fragile X syndrome.

    Science.gov (United States)

    Ghilan, Mohamed; Bettio, Luis E B; Noonan, Athena; Brocardo, Patricia S; Gil-Mohapel, Joana; Christie, Brian R

    2018-05-17

    Fragile X syndrome (FXS) is the most common form of inherited intellectual impairment. The Fmr1 -/y mouse model has been previously shown to have deficits in context discrimination tasks but not in the elevated plus-maze. To further characterize this FXS mouse model and determine whether hippocampal-mediated behaviours are affected in these mice, dentate gyrus (DG)-dependent spatial processing and Cornu ammonis 1 (CA1)-dependent temporal order discrimination tasks were evaluated. In agreement with previous findings of long-term potentiation deficits in the DG of this transgenic model of FXS, the results reported here demonstrate that Fmr1 -/y mice perform poorly in the DG-dependent metric change spatial processing task. However, Fmr1 -/y mice did not present deficits in the CA1-dependent temporal order discrimination task, and were able to remember the order in which objects were presented to them to the same extent as their wild-type littermate controls. These data suggest that the previously reported subregional-specific differences in hippocampal synaptic plasticity observed in the Fmr1 -/y mouse model may manifest as selective behavioural deficits in hippocampal-dependent tasks. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

  3. Sonographic features of gastrointestinal lymphoma in 15 dogs.

    Science.gov (United States)

    Frances, M; Lane, A E; Lenard, Z M

    2013-09-01

    The purpose of this study is to describe the sonographic appearance of lymphoma of the gastrointestinal tract in dogs. A retrospective review was conducted and patients with gastrointestinal lymphoma diagnosed by histopathology (including immunohistochemistry, where available) or cytology that had an abdominal ultrasound were included. Four of 15 (26·7%) cases with histopathologically confirmed lymphoma exhibited no sonographic abnormalities. In the dogs with sonographic abnormalities, features including intestinal wall thickness and the presence or absence of wall layering were highly variable. Clinical signs pertaining to the gastrointestinal tract were also unreliable markers of gastrointestinal lymphoma, with weight loss, vomiting, and diarrhoea being uncommon presenting complaints; intestinal obstruction was not present in any patient. The sonographic appearance of gastrointestinal lymphoma in dogs is non-specific. Gastrointestinal lymphoma in dogs should be maintained as a differential diagnosis despite a sonographically normal appearing bowel. © 2013 British Small Animal Veterinary Association.

  4. Neuropathological assessment and validation of mouse models for Alzheimer's disease: applying NIA-AA guidelines

    Directory of Open Access Journals (Sweden)

    C. Dirk Keene

    2016-06-01

    Full Text Available Dozens of transgenic mouse models, generally based on mutations associated with familial Alzheimer's disease (AD, have been developed, in part, for preclinical testing of candidate AD therapies. However, none of these models has successfully predicted the clinical efficacy of drugs for treating AD patients. Therefore, development of more translationally relevant AD mouse models remains a critical unmet need in the field. A concept not previously implemented in AD preclinical drug testing is the use of mouse lines that have been validated for neuropathological features of human AD. Current thinking suggests that amyloid plaque and neurofibrillary tangle deposition is an essential component for accurate modeling of AD. Therefore, the AD translational paradigm would require pathologic Aβ and tau deposition, a disease-relevant distribution of plaques and tangles, and a pattern of disease progression of Aβ and tau isoforms similar to the neuropathological features found in the brains of AD patients. Additional parameters useful to evaluate parallels between AD and animal models would include 1 cerebrospinal fluid (CSF AD biomarker changes with reduced Aβ and increased phospho-tau/tau; 2 structural and functional neuroimaging patterns including MRI hippocampal atrophy, fluorodeoxyglucose (FDG, and amyloid/tau PET alterations in activity and/or patterns of pathologic peptide deposition and distribution; and 3 cognitive impairment with emphasis on spatial learning and memory to distinguish presymptomatic and symptomatic mice at specific ages. A validated AD mouse model for drug testing would likely show tau-related neurofibrillary degeneration following Aβ deposition and demonstrate changes in pathology, CSF analysis, and neuroimaging that mirror human AD. Development of the ideal model would revolutionize the ability to establish the translational value of AD mouse models and serve as a platform for discussions about national phenotyping guidelines

  5. A dystrophic Duchenne mouse model for testing human antisense oligonucleotides.

    Directory of Open Access Journals (Sweden)

    Marcel Veltrop

    Full Text Available Duchenne muscular dystrophy (DMD is a severe muscle-wasting disease generally caused by reading frame disrupting mutations in the DMD gene resulting in loss of functional dystrophin protein. The reading frame can be restored by antisense oligonucleotide (AON-mediated exon skipping, allowing production of internally deleted, but partially functional dystrophin proteins as found in the less severe Becker muscular dystrophy. Due to genetic variation between species, mouse models with mutations in the murine genes are of limited use to test and further optimize human specific AONs in vivo. To address this we have generated the del52hDMD/mdx mouse. This model carries both murine and human DMD genes. However, mouse dystrophin expression is abolished due to a stop mutation in exon 23, while the expression of human dystrophin is abolished due to a deletion of exon 52. The del52hDMD/mdx model, like mdx, shows signs of muscle dystrophy on a histological level and phenotypically mild functional impairment. Local administration of human specific vivo morpholinos induces exon skipping and dystrophin restoration in these mice. Depending on the number of mismatches, occasional skipping of the murine Dmd gene, albeit at low levels, could be observed. Unlike previous models, the del52hDMD/mdx model enables the in vivo analysis of human specific AONs targeting exon 51 or exon 53 on RNA and protein level and muscle quality and function. Therefore, it will be a valuable tool for optimizing human specific AONs and genome editing approaches for DMD.

  6. The impact of mouse passaging of Mycobacterium tuberculosis strains prior to virulence testing in the mouse and guinea pig aerosol models.

    Directory of Open Access Journals (Sweden)

    Paul J Converse

    2010-04-01

    Full Text Available It has been hypothesized that the virulence of lab-passaged Mycobacterium tuberculosis and recombinant M. tuberculosis mutants might be reduced due to multiple in vitro passages, and that virulence might be augmented by passage of these strains through mice before quantitative virulence testing in the mouse or guinea pig aerosol models.By testing three M. tuberculosis H37Rv samples, one deletion mutant, and one recent clinical isolate for survival by the quantitative organ CFU counting method in mouse or guinea pig aerosol or intravenous infection models, we could discern no increase in bacterial fitness as a result of passaging of M. tuberculosis strains in mice prior to quantitative virulence testing in two animal models. Surface lipid expression as assessed by neutral red staining and thin-layer chromatography for PDIM analysis also failed to identify virulence correlates.These results indicate that animal passaging of M. tuberculosis strains prior to quantitative virulence testing in mouse or guinea pig models does not enhance or restore potency to strains that may have lost virulence due to in vitro passaging. It is critical to verify virulence of parental strains before genetic manipulations are undertaken and comparisons are made.

  7. Plasma Cell-Free DNA in Paediatric Lymphomas

    Science.gov (United States)

    Mussolin, Lara; Burnelli, Roberta; Pillon, Marta; Carraro, Elisa; Farruggia, Piero; Todesco, Alessandra; Mascarin, Maurizio; Rosolen, Angelo

    2013-01-01

    Background: Extracellular circulating DNA (cfDNA) can be found in small amounts in plasma of healthy individuals. Increased levels of cfDNA have been reported in patients with cancer of breast, cervix, colon, liver and it was shown that cfDNA can originate from both tumour and non-tumour cells. Objectives: Levels of cfDNA of a large series of children with lymphoma were evaluated and analyzed in relation with clinical characteristics. Methods: plasma cfDNA levels obtained at diagnosis in 201 paediatric lymphoma patients [43 Hodgkin lymphomas (HL), 45 anaplastic large cell lymphomas (ALCL), 88 Burkitt lymphomas (BL), 17 lymphoblastic (LBL), 8 diffuse large B cell lymphoma (DLBCL)] and 15 healthy individuals were determined using a quantitative PCR assay for POLR2 gene and, in addition, for NPM-ALK fusion gene in ALCL patients. Wilcoxon rank sum test was used to compare plasma levels among different patient subgroups and controls and to analyze relationship between levels of cfDNA and clinical characteristics. Results: Levels of cfDNA in lymphoma patients were significantly higher compared with controls (p<0.0001). CfDNA was associated with median age (p=0.01) in HL, and with stage in ALCL (p=0.01). In HL patients high cfDNA levels were correlated with poor prognosis (p=0.03). In ALCL we found that most of the cfDNA (77%) was non-tumor DNA. Conclusion: level of plasma cfDNA might constitute an important non-invasive tool at diagnosis in lymphoma patients' management; in particular in patients with HL, cfDNA seems to be a promising prognostic biomarker. PMID:23678368

  8. Contrast enhanced ultrasound of splenic lymphoma involvement

    International Nuclear Information System (INIS)

    Goerg, Christian; Faoro, Charis; Bert, Tillmann; Tebbe, Johannes; Neesse, Albrecht; Wilhelm, Christian

    2011-01-01

    Objective: The aim of this study was to compare the value of contrast-enhanced ultrasonography (CEUS) with standard B-mode ultrasound (US) for diagnosis of splenic lymphoma involvement. Methods: From 04/2005 to 10/2008 n = 250 lymphoma patients were investigated by standard B-mode US. A homogeneous splenic echotexture was found in 199 patients (79%). To clarify the benefit of CEUS in this group a pilot series was performed with 16 of the 199 lymphoma patients. All patients with an abnormal splenic echotexture on standard B-Mode US (n = 51) including focal hypoechoic splenic lesions (n = 41) and an inhomogeneous splenic texture (n = 10) were studied by CEUS. CEUS data were retrospectively evaluated. The diagnoses included indolent lymphoma (n = 27), aggressive lymphoma (n = 14), and Hodgkin's disease (n = 10). Number and size of lesions were determined by B-mode US and CEUS. The visualisation of splenic lymphoma involvement by CEUS in comparison to B-mode US was classified as worse, equal, or better. Results: All patients with a homogeneous spleen on B-mode US (n = 16) had no visible focal lesions on CEUS. Study patients with focal lesions (n = 41) had a hypoechoic (n = 22) or isoechoic (n = 19) enhancement during the arterial phase, and a hypoechoic enhancement during the parenchymal phase (n = 41). The visualisation of focal splenic lymphoma was equal (n = 32), better (n = 6), or worse (n = 3). In all study patients with an inhomogeneous spleen on B-mode US (n = 10) no focal lesions were found by CEUS and the value of CEUS therefore was classified as worse. Conclusion: CEUS has no clear advantage for diagnosis of splenic lymphoma involvement.

  9. Contrast enhanced ultrasound of splenic lymphoma involvement

    Energy Technology Data Exchange (ETDEWEB)

    Goerg, Christian, E-mail: goergc@med.uni-marburg.de [Medizinische Universitaetsklinik, Baldingerstrasse, 35033 Marburg/Lahn (Germany); Faoro, Charis [Medizinische Universitaetsklinik, Baldingerstrasse, 35033 Marburg/Lahn (Germany); Bert, Tillmann [Zentralklinik Bad Berka GmbH, Robert-Koch-Allee 9, 99437 Bad Berka (Germany); Tebbe, Johannes [Klinikum Lippe-Detmold, Roentgenstrasse 18, 32756 Detmold (Germany); Neesse, Albrecht; Wilhelm, Christian [Medizinische Universitaetsklinik, Baldingerstrasse, 35033 Marburg/Lahn (Germany)

    2011-11-15

    Objective: The aim of this study was to compare the value of contrast-enhanced ultrasonography (CEUS) with standard B-mode ultrasound (US) for diagnosis of splenic lymphoma involvement. Methods: From 04/2005 to 10/2008 n = 250 lymphoma patients were investigated by standard B-mode US. A homogeneous splenic echotexture was found in 199 patients (79%). To clarify the benefit of CEUS in this group a pilot series was performed with 16 of the 199 lymphoma patients. All patients with an abnormal splenic echotexture on standard B-Mode US (n = 51) including focal hypoechoic splenic lesions (n = 41) and an inhomogeneous splenic texture (n = 10) were studied by CEUS. CEUS data were retrospectively evaluated. The diagnoses included indolent lymphoma (n = 27), aggressive lymphoma (n = 14), and Hodgkin's disease (n = 10). Number and size of lesions were determined by B-mode US and CEUS. The visualisation of splenic lymphoma involvement by CEUS in comparison to B-mode US was classified as worse, equal, or better. Results: All patients with a homogeneous spleen on B-mode US (n = 16) had no visible focal lesions on CEUS. Study patients with focal lesions (n = 41) had a hypoechoic (n = 22) or isoechoic (n = 19) enhancement during the arterial phase, and a hypoechoic enhancement during the parenchymal phase (n = 41). The visualisation of focal splenic lymphoma was equal (n = 32), better (n = 6), or worse (n = 3). In all study patients with an inhomogeneous spleen on B-mode US (n = 10) no focal lesions were found by CEUS and the value of CEUS therefore was classified as worse. Conclusion: CEUS has no clear advantage for diagnosis of splenic lymphoma involvement.

  10. General Information about Adult Hodgkin Lymphoma

    Science.gov (United States)

    ... Lymphocyte-rich classical Hodgkin lymphoma. Age, gender, and Epstein-Barr infection can affect the risk of adult Hodgkin lymphoma. Anything that increases your risk of getting a disease is called a risk factor . Having a risk ...

  11. Dissecting the gray zone between follicular lymphoma and marginal zone lymphoma using morphological and genetic features

    NARCIS (Netherlands)

    Krijgsman, Oscar; Gonzalez, Patricia; Ponz, Olga Balague; Roemer, Margaretha G. M.; Slot, Stefanie; Broeks, Annegien; Braaf, Linde; Kerkhoven, Ron M.; Bot, Freek; van Groningen, Krijn; Beijert, Max; Ylstra, Bauke; de Jongi, Daphne

    2013-01-01

    Nodal marginal zone lymphoma is a poorly defined entity in the World Health Organization classification, based largely on criteria of exclusion and the diagnosis often remains subjective. Follicular lymphoma lacking t(14;18) has similar characteristics which results in a major potential diagnostic

  12. Mouse Chromosome Engineering for Modeling Human Disease

    OpenAIRE

    van der Weyden, Louise; Bradley, Allan

    2006-01-01

    Chromosomal rearrangements occur frequently in humans and can be disease-associated or phenotypically neutral. Recent technological advances have led to the discovery of copy-number changes previously undetected by cytogenetic techniques. To understand the genetic consequences of such genomic changes, these mutations need to be modeled in experimentally tractable systems. The mouse is an excellent organism for this analysis because of its biological and genetic similarity to humans, and the e...

  13. Autoimmune/Inflammatory Arthritis Associated Lymphomas: Who Is at Risk?

    Directory of Open Access Journals (Sweden)

    Sujani Yadlapati

    2016-01-01

    Full Text Available Specific autoimmune and inflammatory rheumatic diseases have been associated with an increased risk of malignant lymphomas. Conditions such as rheumatoid arthritis (RA, primary Sjögren’s syndrome (pSS, systemic lupus erythematosus (SLE, dermatomyositis, and celiac disease have been consistently linked to malignant lymphomas. Isolated cases of lymphomas associated with spondyloarthropathies and autoinflammatory diseases have also been reported. Direct association between autoimmunity and lymphomagenesis has been reinforced by large epidemiological studies. It is still uncertain whether disease specific determinants or phenotypic or treatment related characteristics increase likelihood of lymphomagenesis in these patients. For example, recent literature has indicated a positive correlation between severity of inflammation and risk of lymphomas among RA and Sjögren’s syndrome patients. It is also debated whether specific lymphoma variants are more commonly seen in accordance with certain chronic autoimmune arthritis. Previous studies have revealed a higher incidence of diffuse large B-cell lymphomas in RA and SLE patients, whereas pSS has been linked with increased risk of mucosa-associated lymphoid tissue lymphoma. This review summarizes recent literature evaluating risk of lymphomas in arthritis patients and disease specific risk determinants. We also elaborate on the association of autoimmune arthritis with specific lymphoma variants along with genetic, environmental, and therapeutic risk factors.

  14. A Rare Case of Primary Breast Mucosa- Associated Lymphoid Tissue Lymphoma

    Directory of Open Access Journals (Sweden)

    Marić Daliborka

    2016-12-01

    Full Text Available Breast involvement by lymphoma is uncommon and poses challenges in diagnosis. Breast involvement by malignant lymphoma, whether primary or secondary, is a rare event. Primary breast lymphomas account for 0.38% - 0.7% of all non-Hodgkin lymphomas, 1.7%-2.2% of all extranodal non-Hodgkin lymphomas, and only 0.04% - 0.5% of all breast cancer cases. Most frequent primary breast lymphomas are diffuse large B cell lymphomas (53%. Breast mucosa-associated lymphoid tissue (MALT lymphomas account for a small fraction of all the MALT lymphomas (1% - 2%. Herein we report a case of a patient with primary breast MALT lymphoma and its presentation on different imaging modalities. Two years after the presentation and treatment with eight cycles of chemotherapy, the patient is alive and well, without evidence of residual disease or recurrence.

  15. Primary Testicular B-cell Lymphoma

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    Aykut Buğra Şentürk

    2015-12-01

    Full Text Available Primary testicular lymphoma constitutes only 1-7% of all testicular neoplasms and less than 1% of all non-Hodgkin lymphoma. We report a 69-year-old man who presented with a painful right testicular mass. Treatment modalities consist of surgical excision, chemotherapy and radiation therapy, however there are no standardized treatment options.

  16. Ki-67 is a valuable prognostic predictor of lymphoma but its utility varies in lymphoma subtypes: evidence from a systematic meta-analysis

    International Nuclear Information System (INIS)

    He, Xin; Chen, Zhigang; Fu, Tao; Jin, Xueli; Yu, Teng; Liang, Yun; Zhao, Xiaoying; Huang, Liansheng

    2014-01-01

    Ki-67 is a nuclear protein involved in cell proliferation regulation, and its expression has been widely used as an index to evaluate the proliferative activity of lymphoma. However, its prognostic value for lymphoma is still contradictory and inconclusive. PubMed and Web of Science databases were searched with identical strategies. The impact of Ki-67 expression on survival with lymphoma and various subtypes of lymphoma was evaluated. The relationship between Ki-67 expression and Diffuse Large B Cell Lymphoma (DLBCL) and Mantle Cell Lymphoma (MCL) was also investigated after the introduction of a CD-20 monoclonal antibody rituximab. Furthermore, we evaluated the association between Ki-67 expression and the clinical-pathological features of lymphoma. A total of 27 studies met the inclusion criteria, which comprised 3902 patients. Meta-analysis suggested that high Ki-67 expression was negatively associated with disease free survival (DFS) (HR = 1.727, 95% CI: 1.159-2.571) and overall survival (OS) (HR = 1.7, 95% CI: 1.44-2) for lymphoma patients. Subgroup analysis on the different subtypes of lymphoma suggested that the association between high Ki-67 expression and OS in Hodgkin Lymphoma (HR = 1.511, 95% CI: 0.524-4.358) was absent, while high Ki-67 expression was highly associated with worse OS for Non-Hodgkin Lymphoma (HR = 1.777, 95% CI: 1.463-2.159) and its various subtypes, including NK/T lymphoma (HR = 4.766, 95% CI: 1.917-11.849), DLBCL (HR = 1.457, 95% CI: 1.123-1.891) and MCL (HR = 2.48, 95% CI: 1.61-3.81). Furthermore, the pooled HRs for MCL was 1.981 (95% CI: 1.099-3.569) with rituximab and 3.123 (95% CI: 2.049-4.76) without rituximab, while for DLBCL, the combined HRs for DLBCL with and without rituximab was 1.459 (95% CI: 1.084-2.062) and 1.456 (95% CI: 0.951-2.23) respectively. In addition, there was no correlation between high Ki-67 expression and the clinical-pathological features of lymphoma including the LDH level, B symptoms, tumor stage

  17. Analysis of perfusion weighted image of CNS lymphoma

    International Nuclear Information System (INIS)

    Lee, In Ho; Kim, Sung Tae; Kim, Hyung-Jin; Kim, Keon Ha; Jeon, Pyoung; Byun, Hong Sik

    2010-01-01

    Purpose: It is difficult to differentiate CNS lymphoma from other tumors such as malignant gliomas, metastases, or meningiomas with conventional MR imaging, because the imaging findings are overlapped between these tumors. The purpose of this study is to investigate the perfusion weighted MR imaging findings of CNS lymphomas and to compare the relative cerebral blood volume ratios between CNS lymphomas and other tumors such as high grade gliomas, metastases, or meningiomas. Materials and methods: We retrospectively reviewed MRI findings and clinical records in 13 patients with pathologically proven CNS lymphoma between January 2006 and November 2008. We evaluated the relative cerebral blood volume ratios of tumor, which were obtained by dividing the values obtained from the normal white matter on MRI. Results: Total 13 patients (M:F = 8:5; age range 46-67 years, mean age 52.3 years) were included. The CNS lymphomas showed relatively low values of maximum relative CBV ratio in most patients regardless of primary or secondary CNS lymphoma. Conclusion: Perfusion weighted image may be helpful in the diagnosis of CNS lymphoma in spite of primary or secondary or B cell or T cell.

  18. [Relationship between sensitivity of tumor cells to chemotherapeutic agent in vivo and in vitro: experiment with mouse lymphoma cells].

    Science.gov (United States)

    Li, Chuan-gang; Li, Mo-lin; Shu, Xiao-hong; Jia, Yu-jie; Liu, Yong-ji; Li, Ming

    2007-06-12

    To study the relationship of the sensitivity of tumor cells to chemotherapeutic agent between in vivo and in vitro. Mouse lymphoma cells of the line E14 were cultured and melphalan resistant EL4 cell line (EL4/melphalan) was established by culturing EL4 cells with continuous low-concentration and intermittent gradually-increasing-concentration of melphalan in vitro. MTT assay was used to evaluate the drug sensitivity and the resistance index of the EL4/melphalan cells to melphalan was calculated. EL4/melphalan and EL4 cells of the concentration of 5 x 10(8)/L were inoculated separately into 20 C57BL/6 mice subcutaneously. 12 days later, the EL4 and EL4/melphalan tumor-bearing mice were randomly divided into 2 groups respectively, 5 mice in each group. Treatment groups were given 7.5 mg/kg melphalan intraperitoneally, and control groups were given the same volume of normal saline. The tumor size was observed every other day. Compared with the EL4 cells, the EL4/melphalan cells had no obvious changes morphologically. They could grow in RPMI 1640 medium containing 5 mg/ml melphalan. The resistance index was 2.87 against melphalan. After the treatment of melphalan of the dose 7.5 mg/kg, the tumor sizes of the treatment groups and control groups inoculated with both EL4 cells and the EL4/melphalan cells gradually decreased at the similar speed, and about one week later all tumors disappeared. However, the tumors of the control groups grew progressively and all the mice died at last. The chemotherapeutic effects of tumors in vivo have nothing to do with the effects of the chemotherapeutic agents on tumor cells in vitro. The tumor cells resistant to melphalan in vitro remain sensitive to the drug in vivo.

  19. Revisiting the mouse model of oxygen-induced retinopathy

    Directory of Open Access Journals (Sweden)

    Kim CB

    2016-05-01

    Full Text Available Clifford B Kim,1,2 Patricia A D’Amore,2–4 Kip M Connor1,2 1Angiogenesis Laboratory, Massachusetts Eye and Ear, 2Department of Ophthalmology, Harvard Medical School, 3Schepens Eye Research Institute, Massachusetts Eye and Ear, 4Department of Pathology, Harvard Medical School, Boston, MA, USA Abstract: Abnormal blood vessel growth in the retina is a hallmark of many retinal diseases, such as retinopathy of prematurity (ROP, proliferative diabetic retinopathy, and the wet form of age-related macular degeneration. In particular, ROP has been an important health concern for physicians since the advent of routine supplemental oxygen therapy for premature neonates more than 70 years ago. Since then, researchers have explored several animal models to better understand ROP and retinal vascular development. Of these models, the mouse model of oxygen-induced retinopathy (OIR has become the most widely used, and has played a pivotal role in our understanding of retinal angiogenesis and ocular immunology, as well as in the development of groundbreaking therapeutics such as anti-vascular endothelial growth factor injections for wet age-related macular degeneration. Numerous refinements to the model have been made since its inception in the 1950s, and technological advancements have expanded the use of the model across multiple scientific fields. In this review, we explore the historical developments that have led to the mouse OIR model utilized today, essential concepts of OIR, limitations of the model, and a representative selection of key findings from OIR, with particular emphasis on current research progress. Keywords: ROP, OIR, angiogenesis

  20. Computed tomography in intracranial malignant lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Naruse, S; Odake, G; Fujimoto, M; Yamaki, T; Mizukawa, N [Kyoto Prefectural Univ. of Medicine (Japan)

    1978-09-01

    Malignant lymphoma of the central nervous system has been found more and more often in recent years, partly because of the increased use of radiation and such drugs as steroids and antibiotics. However, the definite diagnosis of this disease is difficult until histological verification has been done by operation or autopsy. Since the revolutionary development of computed tomography, however, several reports have been presented, on the computed tomography of malignant lymphoma of the thorax and abdomen. Nevertheless, only a few cases of intracranial malignant lymphoma have been reported. The purpose of this paper, using four patients, is to emphasize the value of computed tomography in the diagnosis of intracranial malignant lymphoma. The characteristic CT findings of intracranial malignant lymphoma may be summarized follows: (1) the tumors are demonstrated to be well-defined, nodular-shaped, and homogenous isodensity - or slightly high-density - lesions in plain scans, and the tumors homogenously increase in density upon contrast enhancement; (2) the disease always has multifocal intracranial lesions, which are shown simultaneously or one after another, and (3) perifocal edema is prominent around the tumors in the cerebral hemisphere.

  1. Type distribution of lymphomas in Lebanon: five-year single institution experience.

    Science.gov (United States)

    Sader-Ghorra, Claude; Rassy, Marc; Naderi, Samah; Kourie, Hampig Raphael; Kattan, Joseph

    2014-01-01

    Lymphomas represent the fifth most frequent cancer in Lebanon. However, little is known concerning epidemiologic characteristics and distribution of lymphoid neoplasms according to the 2008 WHO classification. We conducted a retrospective study of lymphoma cases diagnosed from 2008 till 2012 at Hotel-Dieu de France University Hospital. A total of 502 new cases of lymphoma were diagnosed at our institution during a five year period: 119 cases (24%) were Hodgkin lymphomas (HL) and 383 cases (76%) were non-Hodgkin lymphomas (NHL). HLs were equally distributed in both sexes with a mean age at diagnosis of 30 years. Among NHL, 87% (332 cases) were B cell lymphomas, 9% (34 cases) were T cell lymphomas and 4%(17 cases) were classified as precursor lymphoid neoplasms. Among B cell lymphomas, 44% (147 cases) were diffuse large B cell lymphomas (DLBCL), 20% (65 cases) follicular lymphomas and 8% (27 cases) mantle cell lymphomas. DLBCL were equally distributed in both sexes with a mean age of 58 years. Follicular lymphomas were characterized by a male predominance (57%) and a mean age of 60 years. Mantle cell lymphomas showed a pronounced male predominance (85%) with a mean age of 60 years in men and 70 years in women. Some 72% of patients having T cell lymphomas were men, with a mean age of 57 years in men and 45 years in women, while 65% of patients having precursor lymphoid neoplasms were women with a mean age of 22 years in women and 30 years in men. The lymphoma subtype distribution in Lebanon is unique when compared to other countries from around the world. In fact, Hodgkin and follicular lymphomas are more frequent than in most Far Eastern, European and American countries, while T-cell lymphomas and DLBCL are less frequent.

  2. Mouse Xenograft Model for Mesothelioma | NCI Technology Transfer Center | TTC

    Science.gov (United States)

    The National Cancer Institute is seeking parties interested in collaborative research to co-develop, evaluate, or commercialize a new mouse model for monoclonal antibodies and immunoconjugates that target malignant mesotheliomas. Applications of the technology include models for screening compounds as potential therapeutics for mesothelioma and for studying the pathology of mesothelioma.

  3. HUPO BPP Workshop on Mouse Models for Neurodegeneration--Choosing the right models.

    Science.gov (United States)

    Hamacher, Michael; Marcus, Katrin; Stephan, Christian; van Hall, Andre; Meyer, Helmut E

    2005-09-01

    The HUPO Brain Proteome Project met during the 4th Dutch Endo-Neuro-Psycho Meeting in Doorwerth, The Netherlands, on June 1, 2005, in order to discuss appropriate (mouse) models for neurodegenerative diseases as well as to conceptualise sophisticated proteomics analyses strategies. Here, the topics of the meeting are summarised.

  4. V-cbl, an oncogene from a dual-recombinant murine retrovirus that induces early B-lineage lymphomas

    International Nuclear Information System (INIS)

    Langdon, W.Y.; Klinken, S.P.; Hartley, J.W.; Morse, H.C. III; Ruscetti, S.K.

    1989-01-01

    Cas NS-1 is an acutely transforming murine retrovirus that induces pre-B and pro-B cell lymphomas. Molecular cloning showed it was generated from the ecotropic Cas-Br-M virus by sequential recombinations with endogenous retroviral sequences and a cellular oncogene. The oncogene sequence shows no homology with known oncogenes but some similarity to the yeast transcriptional activator GCN4. A 100-kDa gag-cbl fusion protein, with no detectable kinase activity, is responsible for the cellular transformation. The cellular homologue of v-cbl, present in mouse and human DNA, is expressed in a range of hemopoietic lineages

  5. Intrathymic injection of hematopoietic progenitor cells establishes functional T cell development in a mouse model of severe combined immunodeficiency

    Directory of Open Access Journals (Sweden)

    Andrea Z. Tuckett

    2017-05-01

    Full Text Available Abstract Background Even though hematopoietic stem cell transplantation can be curative in patients with severe combined immunodeficiency, there is a need for additional strategies boosting T cell immunity in individuals suffering from genetic disorders of lymphoid development. Here we show that image-guided intrathymic injection of hematopoietic stem and progenitor cells in NOD-scid IL2rγnull mice is feasible and facilitates the generation of functional T cells conferring protective immunity. Methods Hematopoietic stem and progenitor cells were isolated from the bone marrow of healthy C57BL/6 mice (wild-type, Luciferase+, CD45.1+ and injected intravenously or intrathymically into both male and female, young or aged NOD-scid IL2rγnull recipients. The in vivo fate of injected cells was analyzed by bioluminescence imaging and flow cytometry of thymus- and spleen-derived T cell populations. In addition to T cell reconstitution, we evaluated mice for evidence of immune dysregulation based on diabetes development and graft-versus-host disease. T cell immunity following intrathymic injection of hematopoietic stem and progenitor cells in NOD-scid IL2rγnull mice was assessed in a B cell lymphoma model. Results Despite the small size of the thymic remnant in NOD-scid IL2rγnull mice, we were able to accomplish precise intrathymic delivery of hematopoietic stem and progenitor cells by ultrasound-guided injection. Thymic reconstitution following intrathymic injection of healthy allogeneic hematopoietic cells was most effective in young male recipients, indicating that even in the setting of severe immunodeficiency, sex and age are important variables for thymic function. Allogeneic T cells generated in intrathymically injected NOD-scid IL2rγnull mice displayed anti-lymphoma activity in vivo, but we found no evidence for severe auto/alloreactivity in T cell-producing NOD-scid IL2rγnull mice, suggesting that immune dysregulation is not a major concern

  6. Evaluation of an in vitro toxicogenetic mouse model for hepatotoxicity

    International Nuclear Information System (INIS)

    Martinez, Stephanie M.; Bradford, Blair U.; Soldatow, Valerie Y.; Kosyk, Oksana; Sandot, Amelia; Witek, Rafal; Kaiser, Robert; Stewart, Todd; Amaral, Kirsten; Freeman, Kimberly; Black, Chris; LeCluyse, Edward L.; Ferguson, Stephen S.; Rusyn, Ivan

    2010-01-01

    Numerous studies support the fact that a genetically diverse mouse population may be useful as an animal model to understand and predict toxicity in humans. We hypothesized that cultures of hepatocytes obtained from a large panel of inbred mouse strains can produce data indicative of inter-individual differences in in vivo responses to hepato-toxicants. In order to test this hypothesis and establish whether in vitro studies using cultured hepatocytes from genetically distinct mouse strains are feasible, we aimed to determine whether viable cells may be isolated from different mouse inbred strains, evaluate the reproducibility of cell yield, viability and functionality over subsequent isolations, and assess the utility of the model for toxicity screening. Hepatocytes were isolated from 15 strains of mice (A/J, B6C3F1, BALB/cJ, C3H/HeJ, C57BL/6J, CAST/EiJ, DBA/2J, FVB/NJ, BALB/cByJ, AKR/J, MRL/MpJ, NOD/LtJ, NZW/LacJ, PWD/PhJ and WSB/EiJ males) and cultured for up to 7 days in traditional 2-dimensional culture. Cells from B6C3F1, C57BL/6J, and NOD/LtJ strains were treated with acetaminophen, WY-14,643 or rifampin and concentration-response effects on viability and function were established. Our data suggest that high yield and viability can be achieved across a panel of strains. Cell function and expression of key liver-specific genes of hepatocytes isolated from different strains and cultured under standardized conditions are comparable. Strain-specific responses to toxicant exposure have been observed in cultured hepatocytes and these experiments open new opportunities for further developments of in vitro models of hepatotoxicity in a genetically diverse population.

  7. Modification of radiation-induced murine thymic lymphoma incidence by curcumin

    International Nuclear Information System (INIS)

    Dange, P.S.; Yadav, H.D.; Kumar, Vimalesh; Bhilwade, H.N.; Pandey, B.N.; Sarma, H.D.

    2017-01-01

    Curcumin is a known antioxidant, preventing radiation damage including carcinogenesis. However, concentration and feeding schedule of curcumin in modification of radiation induced thymic lymphoma incidence in vivo model has not been studied. We report here modification of incidence of γ-radiation-induced thymic lymphoma in mice fed with different doses of curcumin (0.05 to 1 %) in diet. Results: Female Swiss mice (6-8 weeks) fed with normal diet and exposed to 3 Gy whole body "6"0Co γ-irradiation (WBI) showed 85 % incidence of thymic lymphoma (TL) at 120 days post-irradiation. A concentration of 1 % curcumin was found the most effective in TL incidence prevention than other fed concentrations. The TL incidence was remarkably reduced when curcumin was fed to the mice before than after the radiation exposure. These results suggest modification of TL incidence by curcumin in irradiated mice involving DNA damage and apoptotic death mechanisms

  8. Dissecting the regulatory microenvironment of a large animal model of non-Hodgkin lymphoma: evidence of a negative prognostic impact of FOXP3+ T cells in canine B cell lymphoma.

    Directory of Open Access Journals (Sweden)

    Dammy Pinheiro

    Full Text Available The cancer microenvironment plays a pivotal role in oncogenesis, containing a number of regulatory cells that attenuate the anti-neoplastic immune response. While the negative prognostic impact of regulatory T cells (Tregs in the context of most solid tissue tumors is well established, their role in lymphoid malignancies remains unclear. T cells expressing FOXP3 and Helios were documented in the fine needle aspirates of affected lymph nodes of dogs with spontaneous multicentric B cell lymphoma (BCL, proposed to be a model for human non-Hodgkin lymphoma. Multivariable analysis revealed that the frequency of lymph node FOXP3(+ T cells was an independent negative prognostic factor, impacting both progression-free survival (hazard ratio 1.10; p = 0.01 and overall survival (hazard ratio 1.61; p = 0.01 when comparing dogs showing higher than the median FOXP3 expression with those showing the median value of FOXP3 expression or less. Taken together, these data suggest the existence of a population of Tregs operational in canine multicentric BCL that resembles thymic Tregs, which we speculate are co-opted by the tumor from the periphery. We suggest that canine multicentric BCL represents a robust large animal model of human diffuse large BCL, showing clinical, cytological and immunophenotypic similarities with the disease in man, allowing comparative studies of immunoregulatory mechanisms.

  9. [First-line treatment of lymphomas of "high grade malignancy" or "aggressive lymphomas"].

    Science.gov (United States)

    Reyes, F

    2001-11-01

    Main strategies used as first line treatment of aggressive lymphoma are the subject of this review. The evolution of histopathlogical classifications is reviewed and the concept of aggressive lymphoma is given. General principles of chemotherapy treatment and main prognostic factors that direct therapeutic decisions are described. The treatment modalities of localized and advanced disease are detailed, as well as the role of high-dose therapy with hematopoietic support. Finally, the major impact of immunotherapy based on the monoclonal anti-CD20 antibody is envisaged.

  10. Combination of arsenic and interferon-α inhibits expression of KSHV latent transcripts and synergistically improves survival of mice with primary effusion lymphomas.

    Science.gov (United States)

    El Hajj, Hiba; Ali, Jihane; Ghantous, Akram; Hodroj, Dana; Daher, Ahmad; Zibara, Kazem; Journo, Chloé; Otrock, Zaher; Zaatari, Ghazi; Mahieux, Renaud; El Sabban, Marwan; Bazarbachi, Ali; Abou Merhi, Raghida

    2013-01-01

    Kaposi sarcoma-associated herpesvirus (KSHV) is the etiologic agent of primary effusion lymphomas (PEL). PEL cell lines infected with KSHV, but negative for Epstein-Barr virus have a tumorigenic potential in non-obese diabetic/severe combined immunodeficient mice and result in efficient engraftment and formation of malignant ascites with notable abdominal distension, consistent with the clinical manifestations of PEL in humans. Using this preclinical mouse model, we demonstrate that the combination of arsenic trioxide and interferon-alpha (IFN) inhibits proliferation, induces apoptosis and downregulates the latent viral transcripts LANA-1, v-FLIP and v-Cyc in PEL cells derived from malignant ascites. Furthermore, this combination decreases the peritoneal volume and synergistically increases survival of PEL mice. These results provide a promising rationale for the therapeutic use of arsenic/IFN in PEL patients.

  11. The mantle cells lymphoma: a proposed treatment

    International Nuclear Information System (INIS)

    Chavez Martinez, Marlene Elizabeth

    2012-01-01

    A literature review was performed on mantle cells lymphoma in the therapeutic schemes. The literature that has been used is published in journals of medicine specializing in hematology, oncology, radiation therapy, molecular biology and internal medicine. The literature review was performed to propose a scheme of treatment according to Costa Rica. Epigenetic alterations have been revealed in patients with mantle lymphoma on current researches. The mantle lymphoma pathology has been described in various forms of clinical and histological presentation, stressing the importance of detailing the different methods and diagnostic reports. Working groups have proposed and developed various chemotherapy regimens and concluded that CHOP alone is without effect in mantle cell lymphoma unlike R-hyper-CVAD, CHOP / DHAP, high-dose Ara-C. Researchers have tried to develop new treatments based vaccines, use of modified viruses, specific monoclonal antibodies. The classic treatment has been triple intrathecal therapy. The central nervous system has been one of the most momentous sites of mantle cell lymphoma infiltration because poorer patient prognosis [es

  12. Abdominal lymphadenopathy in tuberculosis and lymphoma: Differentiation with CT

    International Nuclear Information System (INIS)

    Shin, Yong Moon; Choi, Byung Ihn; Han, Joon Koo; Han, Man Chung; Song, Chi Sung; Yang, Seoung Oh

    1993-01-01

    Tuberculosis and lymphoma, these 2 dieases can present with lymphadenopathy in anywhere of the body. Therefore differentiation of tuberculosis from lymphoma is often difficult. CT scans of 17 patients with tuberculosis and 23 patients with lymphoma were retrospectively reviewed to evaluate the efficacy of CT scans in differentating adenopathy between tuberculosis and lymphoma. All the patients underwent abdominal CT scans with contrast enhancement before treatment. The size, internal architecture, distribution of lymph nodes, and associated findings on CT scans were analyzed. As compared with lymphoma, tuberculous lymphadenopathy showed 1) female preponderance (65%), 2) predilection for percolative lymph nodes (47%), 3) internal low attenuation in lymph nodes (82%), 4) cold abscess formation (24%). Characteristics of lymphoma on CT scans include 1) male preponderance (78%), 2) conglomeration of lymph nodes (39%), 3) homogeneous internal lymph node structure (83%). These results suggest that evaluation of the cahracteristics of lymphadenopathy on CT scans is helpful for differentiating between tuberculousis and lymphoma

  13. Introduction of OX40 ligand into lymphoma cells elicits anti-lymphoma immunity in vivo.

    Science.gov (United States)

    Kaneko, Hitomi; Hori, Toshiyuki; Yanagita, Soshi; Kadowaki, Norimitsu; Uchiyama, Takashi

    2005-03-01

    OX40, a member of the TNF receptor superfamily, and its ligand (OX40L) play crucial roles in induction and maintenance of integrated T cell immune response. Engagement of OX40L delivers a costimulatory signal to T cells. In this study, we investigated whether inoculation of OX40L-transfected EL4, a murine T cell lymphoma cell line, could induce anti-lymphoma immunity in mice. Female C57BL/6 mice were inoculated with 1 x 10(5) cells of parental EL4, OX40L-transfected EL4 (EL4-OX40L), or mock control vector-transfected EL4 (EL4-mock), and then the tumor size, overall survival, CTL activity of spleen cells, and the immunohistochemistry were compared. While both parental EL4 and EL4-mock grew rapidly, EL4-OX40L was rejected or grew slower than parental EL4 or EL4-mock. Pretreatment of mice with either anti-CD4 or anti-CD8 mAb accelerated the growth of EL4-OX40L, suggesting that both CD4+ and CD8+ T cells were involved in anti-lymphoma immunity. The immunohistochemical study revealed the infiltration of CD8+ T cells into the tumor of EL4-OX40L. In vitro CTL assay demonstrated that spleen cells of mice that had rejected EL4-OX40L had significant cytotoxic activity against parental EL4. The gene transfer of OX40L into lymphoma cells is an eligible and efficient modality to induce anti-lymphoma immunity.

  14. Abdominal manifestations of extranodal lymphoma: pictorial essay

    Energy Technology Data Exchange (ETDEWEB)

    Fajardo, Lais; Cardia, Patricia Prando; Prando, Adilson, E-mail: laisfajardo@gmail.com [Centro Radiologico Campinas/Hospital Vera Cruz, Campinas, SP (Brazil); Ramin, Guilherme de Araujo; Penachim, Thiago Jose; Martins, Daniel Lahan [Pontificia Universidade Catolica de Campinas (PUC- Campinas), SP (Brazil)

    2016-11-15

    In the appropriate clinical setting, certain aspects of extranodal abdominal lymphoma, as revealed by current cross-sectional imaging techniques, should be considered potentially diagnostic and can hasten the diagnosis. In addition, diagnostic imaging in the context of biopsy-proven lymphoma can accurately stage the disease for its appropriate treatment. The purpose of this article was to illustrate the various imaging aspects of extranodal lymphoma in the abdomen. (author)

  15. Use of a conformational switching aptamer for rapid and specific ex vivo identification of central nervous system lymphoma in a xenograft model.

    Directory of Open Access Journals (Sweden)

    Joseph F Georges

    Full Text Available Improved tools for providing specific intraoperative diagnoses could improve patient care. In neurosurgery, intraoperatively differentiating non-operative lesions such as CNS B-cell lymphoma from operative lesions can be challenging, often necessitating immunohistochemical (IHC procedures which require up to 24-48 hours. Here, we evaluate the feasibility of generating rapid ex vivo specific labeling using a novel lymphoma-specific fluorescent switchable aptamer. Our B-cell lymphoma-specific switchable aptamer produced only low-level fluorescence in its unbound conformation and generated an 8-fold increase in fluorescence once bound to its target on CD20-positive lymphoma cells. The aptamer demonstrated strong binding to B-cell lymphoma cells within 15 minutes of incubation as observed by flow cytometry. We applied the switchable aptamer to ex vivo xenograft tissue harboring B-cell lymphoma and astrocytoma, and within one hour specific visual identification of lymphoma was routinely possible. In this proof-of-concept study in human cell culture and orthotopic xenografts, we conclude that a fluorescent switchable aptamer can provide rapid and specific labeling of B-cell lymphoma, and that developing aptamer-based labeling approaches could simplify tissue staining and drastically reduce time to histopathological diagnoses compared with IHC-based methods. We propose that switchable aptamers could enhance expeditious, accurate intraoperative decision-making.

  16. Use of a conformational switching aptamer for rapid and specific ex vivo identification of central nervous system lymphoma in a xenograft model.

    Science.gov (United States)

    Georges, Joseph F; Liu, Xiaowei; Eschbacher, Jennifer; Nichols, Joshua; Mooney, Michael A; Joy, Anna; Spetzler, Robert F; Feuerstein, Burt G; Preul, Mark C; Anderson, Trent; Yan, Hao; Nakaji, Peter

    2015-01-01

    Improved tools for providing specific intraoperative diagnoses could improve patient care. In neurosurgery, intraoperatively differentiating non-operative lesions such as CNS B-cell lymphoma from operative lesions can be challenging, often necessitating immunohistochemical (IHC) procedures which require up to 24-48 hours. Here, we evaluate the feasibility of generating rapid ex vivo specific labeling using a novel lymphoma-specific fluorescent switchable aptamer. Our B-cell lymphoma-specific switchable aptamer produced only low-level fluorescence in its unbound conformation and generated an 8-fold increase in fluorescence once bound to its target on CD20-positive lymphoma cells. The aptamer demonstrated strong binding to B-cell lymphoma cells within 15 minutes of incubation as observed by flow cytometry. We applied the switchable aptamer to ex vivo xenograft tissue harboring B-cell lymphoma and astrocytoma, and within one hour specific visual identification of lymphoma was routinely possible. In this proof-of-concept study in human cell culture and orthotopic xenografts, we conclude that a fluorescent switchable aptamer can provide rapid and specific labeling of B-cell lymphoma, and that developing aptamer-based labeling approaches could simplify tissue staining and drastically reduce time to histopathological diagnoses compared with IHC-based methods. We propose that switchable aptamers could enhance expeditious, accurate intraoperative decision-making.

  17. Rare transformation to double hit lymphoma in Waldenstrom's macroglobulinemia.

    Science.gov (United States)

    Okolo, Onyemaechi N; Johnson, Ariel C; Yun, Seongseok; Arnold, Stacy J; Anwer, Faiz

    2017-08-01

    Waldenström macroglobulinemia (WM) is a lymphoproliferative lymphoma that is characterized by monoclonal immunoglobulin M (IgM) protein and bone marrow infiltration. Its incidence is rare and rarer still is its ability to transform to a B-cell lymphoma, particularly the aggressive diffuse large B-cell lymphoma, which bodes a poor prognosis. When transformation includes mutations of MYC, BCL-2 and/or BCL-6, it is known as a 'double hit' or 'triple hit' lymphoma respectively. This paper presents a rare case of WM with mutations positive for MYC and BCL2, making it a case of double hit B-cell lymphoplasmacytic lymphoma with plasmatic differentiation without morphological transformation to aggressive histology like DLBCL. The paper also broadens to include discussions on current topics in the classification, diagnosis, possible causes of transformation, and treatment of WM, including transformation to double hit lymphoma. The significance of this case lies in that the presence of double hit lymphoma-like genetic mutations in WM have not been previously described in the literature and potentially such changes are harbinger of extra-nodal presentation, aggressive growth, and possibly poor prognosis, if data from other double-hit lymphoma are extrapolated.

  18. Pediatric Type Follicular Lymphoma: A Rare Entity with Excellent Prognosis

    Science.gov (United States)

    2018-01-19

    YYYY) 12. REPORT TYPE 19/01/2018 Poster 4. TITLE AND SUBTITLE Pediatric -Type Follicular Lymphoma: A Rare Entity with Excellent Prognosis 6. AUTHOR(S...lymphoma is common in older adults but rare in pediatric and young adult patients. Pediatric follicular lymphoma comprises a only 6.5% of childhood... Pediatric follicular lymphoma is defined by a localized high grade appearing lymphoma that lacks these gene rearrangements. Other diagnoses to rule out

  19. Minimal Residual Disease Assessment in Lymphoma: Methods and Applications.

    Science.gov (United States)

    Herrera, Alex F; Armand, Philippe

    2017-12-01

    Standard methods for disease response assessment in patients with lymphoma, including positron emission tomography and computed tomography scans, are imperfect. In other hematologic malignancies, particularly leukemias, the ability to detect minimal residual disease (MRD) is increasingly influencing treatment paradigms. However, in many subtypes of lymphoma, the application of MRD assessment techniques, like flow cytometry or polymerase chain reaction-based methods, has been challenging because of the absence of readily detected circulating disease or canonic chromosomal translocations. Newer MRD detection methods that use next-generation sequencing have yielded promising results in a number of lymphoma subtypes, fueling the hope that MRD detection may soon be applicable in clinical practice for most patients with lymphoma. MRD assessment can provide real-time information about tumor burden and response to therapy, noninvasive genomic profiling, and monitoring of clonal dynamics, allowing for many possible applications that could significantly affect the care of patients with lymphoma. Further validation of MRD assessment methods, including the incorporation of MRD assessment into clinical trials in patients with lymphoma, will be critical to determine how best to deploy MRD testing in routine practice and whether MRD assessment can ultimately bring us closer to the goal of personalized lymphoma care. In this review article, we describe the methods available for detecting MRD in patients with lymphoma and their relative advantages and disadvantages. We discuss preliminary results supporting the potential applications for MRD testing in the care of patients with lymphoma and strategies for including MRD assessment in lymphoma clinical trials.

  20. Biology and therapy of inherited retinal degenerative disease: insights from mouse models

    Directory of Open Access Journals (Sweden)

    Shobi Veleri

    2015-02-01

    Full Text Available Retinal neurodegeneration associated with the dysfunction or death of photoreceptors is a major cause of incurable vision loss. Tremendous progress has been made over the last two decades in discovering genes and genetic defects that lead to retinal diseases. The primary focus has now shifted to uncovering disease mechanisms and designing treatment strategies, especially inspired by the successful application of gene therapy in some forms of congenital blindness in humans. Both spontaneous and laboratory-generated mouse mutants have been valuable for providing fundamental insights into normal retinal development and for deciphering disease pathology. Here, we provide a review of mouse models of human retinal degeneration, with a primary focus on diseases affecting photoreceptor function. We also describe models associated with retinal pigment epithelium dysfunction or synaptic abnormalities. Furthermore, we highlight the crucial role of mouse models in elucidating retinal and photoreceptor biology in health and disease, and in the assessment of novel therapeutic modalities, including gene- and stem-cell-based therapies, for retinal degenerative diseases.

  1. Mouse models in liver cancer research: A review of current literature

    Science.gov (United States)

    Leenders, Martijn WH; Nijkamp, Maarten W; Rinkes, Inne HM Borel

    2008-01-01

    Primary liver cancer remains one of the most lethal malignancies worldwide. Due to differences in prevalence of etiological factors the incidence of primary liver cancer varies among the world, with a peak in East-Asia. As this disease is still lethal in most of the cases, research has to be done to improve our understanding of the disease, offering insights for possible treatment options. For this purpose, animal models are widely used, especially mouse models. In this review, we describe the different types of mouse models used in liver cancer research, with emphasis on genetically engineered mice used in this field. We focus on hepatocellular carcinoma (HCC), as this is by far the most common type of primary liver cancer, accounting for 70%-85% of cases. PMID:19058325

  2. ESMO Consensus conferences : guidelines on malignant lymphoma. part 2: marginal zone lymphoma, mantle cell lymphoma, peripheral T-cell lymphoma

    NARCIS (Netherlands)

    Dreyling, M.; Thieblemont, C.; Gallamini, A.; Arcaini, L.; Campo, E.; Hermine, O.; Kluin-Nelemans, J. C.; Ladetto, M.; Le Gouill, S.; Iannitto, E.; Pileri, S.; Rodriguez, J.; Schmitz, N.; Wotherspoon, A.; Zinzani, P.; Zucca, E.

    To complement the existing treatment guidelines for all tumour types, ESMO organizes consensus conferences to focus on specific issues in each type of tumour. In this setting, a consensus conference on the management of lymphoma was held on 18 June 2011 in Lugano, next to the 11th International

  3. [Bilateral ovarian Burkitt's lymphoma. A case presentation].

    Science.gov (United States)

    Briseño-Hernández, Andrés Alejandro; Quezada-López, Deissy Roxana; Castañeda-Chávez, Agar; Dassaejv Macías-Amezcua, Michel; Pintor-Belmontes, Julio Cesar

    2014-01-01

    Burkitt lymphoma, is described as an aggressive form of non-Hodgkin lymphoma of B cells which occurs most often in children and young adults, ovarian lymphoma can appear as a primary lesion or more commonly referred to as a metastasis. Primary ovarian lesions are rare manifestations corresponding to 0.5% of non-Hodgkin lymphoma and 1.5% of ovarian tumors. Clinic case: 31 years old female with general weakness, march incapacity, dyspnea, hyporexia, fever, diaphoresis, weight loss of 20 kg, flat abs with abdominal pain; Ca125 610 U/ml. Abdominal computed tomography shows a solid aspect tumor which affects the right pelvic cavity. Bilateral ovarian tumors were removed. Microscopically, both lesions show a "starry sky" pattern composed by a monotonous infiltration of lymphocytes mixed with large and clear macrophages, several atypical mitoses, and necrosis and hemorrhage areas. Immunohistochemistry was positive for CD10, CD20, and negative for CD3 and high Ki67 proliferation index. Bilateral ovarian Burkitt's lymphoma was diagnosed. Bilateral ovarian Burkitt's lymphoma is a rare entity, with a variability of presentations, the abdominal pain and abdominal tumors are the most frequent. The patient's prognosis at short term is poor, therefore it's necessary to know this entity and make an early diagnosis.

  4. Primary parotid gland lymphoma: a case report

    Directory of Open Access Journals (Sweden)

    Paraskevas Katsaronis

    2011-08-01

    Full Text Available Abstract Introduction Mucosa associated lymphoid tissue lymphomas are the most common lymphomas of the salivary glands. The benign lymphoepithelial lesion is also a lymphoproliferative disease that develops in the parotid gland. In the present case report, we describe one case of benign lymphoepithelial lesion with a subsequent low transformation to grade mucosa associated lymphoid tissue lymphoma appearing as a cystic mass in the parotid gland. Case presentation A 78-year-old Caucasian female smoker was referred to our clinic with a non-tender left facial swelling that had been present for approximately three years. The patient underwent resection of the left parotid gland with preservation of the left facial nerve through a preauricular incision. The pathology report was consistent with a low-grade marginal-zone B-cell non-Hodgkin lymphoma (mucosa associated lymphoid tissue lymphoma following benign lymphoepithelial lesion of the gland. Conclusions Salivary gland mucosa associated lymphoid tissue lymphoma should be considered in the differential diagnosis of cystic or bilateral salivary gland lesions. Parotidectomy is recommended in order to treat the tumor and to ensure histological diagnosis for further follow-up planning. Radiotherapy and chemotherapy should be considered in association with surgery in disseminated forms or after removal.

  5. Varied appearance of lymphoma in patients with AIDS

    International Nuclear Information System (INIS)

    Sider, L.; Weiss, A.

    1988-01-01

    Lymphoma is frequently present in patients with acquired immunodeficiency (AIDS). But unlike in the general population, the appearance of lymphoma in patients with AIDS is extremely varied. The computed tomographic scans, chest radiographs, and subsequent hospital courses of 15 patients with AIDS-related lymphoma are presented. The patients presented with isolated pleural effusion (six patients), pleural and pericardial effusion (one patient), pulmonary infiltrates (five patients), and mediastinal adenopathy (three patients). This varied manner of presentation of lymphoma in AIDS patients should be recognized if diagnosis is to be made in the earlier stages of presentation

  6. Primary cutaneous lymphoma

    International Nuclear Information System (INIS)

    Nguyen, M. Connie; Cleary, Sean F.; Hoppe, Richard T.

    1995-01-01

    Purpose: A retrospective review analyzed the survival and freedom from relapse of patients with stage IE or IIE primary cutaneous lymphoma (non mycosis fungoides) after treatments with radiation therapy alone (XRT), chemotherapy alone (RX) or combined modality therapy (CMT). Methods and Materials: Fifty two patients with stage IE-IIE cutaneous lymphoma treated at Stanford University Hospital were reviewed. The median age was 57, with a range of 26 to 94 and a male to female ratio of 1.21:1. Patients were staged according to the Ann Arbor System. Pathology was classified according to the Working Formulation. Treatment outcomes were compared using Kaplan-Meier survival curves with a Gehan p-value test. Results: The follow up range was 6 months to 22 years (median 7 years.) Twenty one percent of patients had low grade, 63% had intermediate grade and 15% had high grade lymphoma. The most common histologic subtype was diffuse large cell lymphoma Thirty two patients received radiation alone as initial treatment and sixteen patients received combined modality as initial treatment. Four patients received chemotherapy alone. The only significant prognostic factor for survival was the stage at diagnosis. Patients with stage IE disease had a longer actuarial survival (5-yr=79%, 10-yr=71%), as compared to those with stage IIE (5-yr=49%, 10-yr=33%), (p=0.029). The only significant prognostic factor for freedom from relapse was the initial treatment. Initial combined modality treatment lead to a longer freedom from relapse compared to patients treated with radiation alone (p=0.002), (median 5 years vs. 1.2 years). Despite this, the actuarial overall survival in the combined modality group and the radiation alone group are similar (median survival 7.7 and 8 years). The efficacy of either radiation or chemotherapy as salvage treatment after radiation failure was equivalent and both salvage treatments lead to equally long survival and freedom from second relapse. Conclusion

  7. Primary cutaneous lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, M Connie; Cleary, Sean F; Hoppe, Richard T

    1995-07-01

    Purpose: A retrospective review analyzed the survival and freedom from relapse of patients with stage IE or IIE primary cutaneous lymphoma (non mycosis fungoides) after treatments with radiation therapy alone (XRT), chemotherapy alone (RX) or combined modality therapy (CMT). Methods and Materials: Fifty two patients with stage IE-IIE cutaneous lymphoma treated at Stanford University Hospital were reviewed. The median age was 57, with a range of 26 to 94 and a male to female ratio of 1.21:1. Patients were staged according to the Ann Arbor System. Pathology was classified according to the Working Formulation. Treatment outcomes were compared using Kaplan-Meier survival curves with a Gehan p-value test. Results: The follow up range was 6 months to 22 years (median 7 years.) Twenty one percent of patients had low grade, 63% had intermediate grade and 15% had high grade lymphoma. The most common histologic subtype was diffuse large cell lymphoma Thirty two patients received radiation alone as initial treatment and sixteen patients received combined modality as initial treatment. Four patients received chemotherapy alone. The only significant prognostic factor for survival was the stage at diagnosis. Patients with stage IE disease had a longer actuarial survival (5-yr=79%, 10-yr=71%), as compared to those with stage IIE (5-yr=49%, 10-yr=33%), (p=0.029). The only significant prognostic factor for freedom from relapse was the initial treatment. Initial combined modality treatment lead to a longer freedom from relapse compared to patients treated with radiation alone (p=0.002), (median 5 years vs. 1.2 years). Despite this, the actuarial overall survival in the combined modality group and the radiation alone group are similar (median survival 7.7 and 8 years). The efficacy of either radiation or chemotherapy as salvage treatment after radiation failure was equivalent and both salvage treatments lead to equally long survival and freedom from second relapse. Conclusion

  8. Distinctive serum miRNA profile in mouse models of striated muscular pathologies.

    Directory of Open Access Journals (Sweden)

    Nicolas Vignier

    Full Text Available Biomarkers are critically important for disease diagnosis and monitoring. In particular, close monitoring of disease evolution is eminently required for the evaluation of therapeutic treatments. Classical monitoring methods in muscular dystrophies are largely based on histological and molecular analyses of muscle biopsies. Such biopsies are invasive and therefore difficult to obtain. The serum protein creatine kinase is a useful biomarker, which is however not specific for a given pathology and correlates poorly with the severity or course of the muscular pathology. The aim of the present study was the systematic evaluation of serum microRNAs (miRNAs as biomarkers in striated muscle pathologies. Mouse models for five striated muscle pathologies were investigated: Duchenne muscular dystrophy (DMD, limb-girdle muscular dystrophy type 2D (LGMD2D, limb-girdle muscular dystrophy type 2C (LGMD2C, Emery-Dreifuss muscular dystrophy (EDMD and hypertrophic cardiomyopathy (HCM. Two-step RT-qPCR methodology was elaborated, using two different RT-qPCR miRNA quantification technologies. We identified miRNA modulation in the serum of all the five mouse models. The most highly dysregulated serum miRNAs were found to be commonly upregulated in DMD, LGMD2D and LGMD2C mouse models, which all exhibit massive destruction of striated muscle tissues. Some of these miRNAs were down rather than upregulated in the EDMD mice, a model without massive myofiber destruction. The dysregulated miRNAs identified in the HCM model were different, with the exception of one dysregulated miRNA common to all pathologies. Importantly, a specific and distinctive circulating miRNA profile was identified for each studied pathological mouse model. The differential expression of a few dysregulated miRNAs in the DMD mice was further evaluated in DMD patients, providing new candidates of circulating miRNA biomarkers for DMD.

  9. Vorinostat in Treating Patients With Metastatic or Unresectable Solid Tumors or Lymphoma and Liver Dysfunction

    Science.gov (United States)

    2014-02-21

    Adult Grade III Lymphomatoid Granulomatosis; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Primary Central Nervous System Hodgkin Lymphoma; Primary Central Nervous System Non-Hodgkin Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage

  10. A mouse model of mitochondrial complex III dysfunction induced by myxothiazol

    Energy Technology Data Exchange (ETDEWEB)

    Davoudi, Mina [Pediatrics, Department of Clinical Sciences, Lund, Lund University, Lund 22185 (Sweden); Kallijärvi, Jukka; Marjavaara, Sanna [Folkhälsan Research Center, Biomedicum Helsinki, University of Helsinki, 00014 (Finland); Kotarsky, Heike; Hansson, Eva [Pediatrics, Department of Clinical Sciences, Lund, Lund University, Lund 22185 (Sweden); Levéen, Per [Pediatrics, Department of Clinical Sciences, Lund, Lund University, Lund 22185 (Sweden); Folkhälsan Research Center, Biomedicum Helsinki, University of Helsinki, 00014 (Finland); Fellman, Vineta, E-mail: Vineta.Fellman@med.lu.se [Pediatrics, Department of Clinical Sciences, Lund, Lund University, Lund 22185 (Sweden); Folkhälsan Research Center, Biomedicum Helsinki, University of Helsinki, 00014 (Finland); Children’s Hospital, Helsinki University Hospital, University of Helsinki, Helsinki 00029 (Finland)

    2014-04-18

    Highlights: • Reversible chemical inhibition of complex III in wild type mouse. • Myxothiazol causes decreased complex III activity in mouse liver. • The model is useful for therapeutic trials to improve mitochondrial function. - Abstract: Myxothiazol is a respiratory chain complex III (CIII) inhibitor that binds to the ubiquinol oxidation site Qo of CIII. It blocks electron transfer from ubiquinol to cytochrome b and thus inhibits CIII activity. It has been utilized as a tool in studies of respiratory chain function in in vitro and cell culture models. We developed a mouse model of biochemically induced and reversible CIII inhibition using myxothiazol. We administered myxothiazol intraperitoneally at a dose of 0.56 mg/kg to C57Bl/J6 mice every 24 h and assessed CIII activity, histology, lipid content, supercomplex formation, and gene expression in the livers of the mice. A reversible CIII activity decrease to 50% of control value occurred at 2 h post-injection. At 74 h only minor histological changes in the liver were found, supercomplex formation was preserved and no significant changes in the expression of genes indicating hepatotoxicity or inflammation were found. Thus, myxothiazol-induced CIII inhibition can be induced in mice for four days in a row without overt hepatotoxicity or lethality. This model could be utilized in further studies of respiratory chain function and pharmacological approaches to mitochondrial hepatopathies.

  11. Primary thoracic epidural lymphoma: A rare cause of spinal cord ...

    African Journals Online (AJOL)

    Spinal epidural lymphoma is a rare entity that is not often considered in the differential diagnosis of an epidural mass in a previously healthy individual. Pfatients with Primary Spinal Epidural Lymphomas (PSELs) have negative diagnostic work up for systemic lymphoma and unlike disseminated lymphoma, they achieve ...

  12. PET/CT presentation of primary effusion lymphoma-like lymphoma unrelated to human herpes virus 8, a rare NHL subtype

    International Nuclear Information System (INIS)

    Patil, Vivek V; Sideras, Panagiotis; Machac, Josef

    2014-01-01

    We present a 71-year-old female with human herpes virus 8 (HHV8)-unrelated primary effusion lymphoma (PEL)-like lymphoma. Dyspnea and pericardial effusion led to pericardiocentesis, diagnosing diffuse large B-cell lymphoma. She underwent positron emission tomography/computed tomography (PET/CT), which demonstrated hypermetabolic pericardial, pleural, and ascites fluid without lymphadenopathy elsewhere. Malignant fluid in the absence of lymphadenopathy is a hallmark of PEL. PEL is associated with immunodeficiency states such as acquired immunodeficiency syndrome (AIDS) and infectious agents such as HHV8. Our patient had no such history and had not received immunosuppressive chemotherapy. We present the PET/CT findings of this rare case of HHV8-unrelated PEL-like lymphoma

  13. Brentuximab Vedotin + Rituximab as Frontline Therapy for Pts w/ CD30+ and/or EBV+ Lymphomas

    Science.gov (United States)

    2015-04-28

    Adult Grade III Lymphomatoid Granulomatosis; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Contiguous Stage II Adult Burkitt Lymphoma; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Contiguous Stage II Adult Lymphoblastic Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Epstein-Barr Virus Infection; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Progressive Hairy Cell Leukemia, Initial Treatment; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis

  14. The Mouse Lemur, a Genetic Model Organism for Primate Biology, Behavior, and Health.

    Science.gov (United States)

    Ezran, Camille; Karanewsky, Caitlin J; Pendleton, Jozeph L; Sholtz, Alex; Krasnow, Maya R; Willick, Jason; Razafindrakoto, Andriamahery; Zohdy, Sarah; Albertelli, Megan A; Krasnow, Mark A

    2017-06-01

    Systematic genetic studies of a handful of diverse organisms over the past 50 years have transformed our understanding of biology. However, many aspects of primate biology, behavior, and disease are absent or poorly modeled in any of the current genetic model organisms including mice. We surveyed the animal kingdom to find other animals with advantages similar to mice that might better exemplify primate biology, and identified mouse lemurs ( Microcebus spp.) as the outstanding candidate. Mouse lemurs are prosimian primates, roughly half the genetic distance between mice and humans. They are the smallest, fastest developing, and among the most prolific and abundant primates in the world, distributed throughout the island of Madagascar, many in separate breeding populations due to habitat destruction. Their physiology, behavior, and phylogeny have been studied for decades in laboratory colonies in Europe and in field studies in Malagasy rainforests, and a high quality reference genome sequence has recently been completed. To initiate a classical genetic approach, we developed a deep phenotyping protocol and have screened hundreds of laboratory and wild mouse lemurs for interesting phenotypes and begun mapping the underlying mutations, in collaboration with leading mouse lemur biologists. We also seek to establish a mouse lemur gene "knockout" library by sequencing the genomes of thousands of mouse lemurs to identify null alleles in most genes from the large pool of natural genetic variants. As part of this effort, we have begun a citizen science project in which students across Madagascar explore the remarkable biology around their schools, including longitudinal studies of the local mouse lemurs. We hope this work spawns a new model organism and cultivates a deep genetic understanding of primate biology and health. We also hope it establishes a new and ethical method of genetics that bridges biological, behavioral, medical, and conservation disciplines, while

  15. Primary amines protect against retinal degeneration in mouse models of retinopathies.

    Science.gov (United States)

    Maeda, Akiko; Golczak, Marcin; Chen, Yu; Okano, Kiichiro; Kohno, Hideo; Shiose, Satomi; Ishikawa, Kaede; Harte, William; Palczewska, Grazyna; Maeda, Tadao; Palczewski, Krzysztof

    2011-12-25

    Vertebrate vision is initiated by photoisomerization of the visual pigment chromophore 11-cis-retinal and is maintained by continuous regeneration of this retinoid through a series of reactions termed the retinoid cycle. However, toxic side reaction products, especially those involving reactive aldehyde groups of the photoisomerized product, all-trans-retinal, can cause severe retinal pathology. Here we lowered peak concentrations of free all-trans-retinal with primary amine-containing Food and Drug Administration (FDA)-approved drugs that did not inhibit chromophore regeneration in mouse models of retinal degeneration. Schiff base adducts between all-trans-retinal and these amines were identified by MS. Adducts were observed in mouse eyes only when an experimental drug protected the retina from degeneration in both short-term and long-term treatment experiments. This study demonstrates a molecular basis of all-trans-retinal-induced retinal pathology and identifies an assemblage of FDA-approved compounds with protective effects against this pathology in a mouse model that shows features of Stargardt's disease and age-related retinal degeneration.

  16. Antibody therapies for lymphoma in children

    NARCIS (Netherlands)

    de Zwart, Verena; Gouw, Samantha C.; Meyer-Wentrup, Friederike A. G.

    2016-01-01

    Lymphomas are the third most common malignancy in childhood. Cure rates are high but have reached a plateau. Therefore new treatment modalities should be developed. Antibody therapy is a successful new treatment option in adult lymphoma. However, none of the therapeutic antibodies available for

  17. Primary lymphocytic lymphoma of lacrimal gland.

    Science.gov (United States)

    Romero-Caballero, M D; Lozano-García, I; Gómez-Molina, C; Gil-Liñán, A I; Arcas, I

    2017-02-01

    We report a case of primary small-cell lymphocytic lacrimal gland lymphoma in a male diagnosed with primary antiphospholipid syndrome. These rare lymphomas are usually presented in the clinic as disseminations secondary to chronic lymphocytic leukaemia, and the primary site is rare in the orbit. Non-Hodgkin lymphomas are a heterogeneous group of tumours. Although treatment in the IE stage is usually radiotherapy, due to its association with antiphospholipid syndrome, systemic treatment with rituximab was administered. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  18. Incidence and risk factors for relapses in HIV-associated non-Hodgkin lymphoma as observed in the German HIV-related lymphoma cohort study.

    Science.gov (United States)

    Schommers, Philipp; Gillor, Daniel; Hentrich, Marcus; Wyen, Christoph; Wolf, Timo; Oette, Mark; Zoufaly, Alexander; Wasmuth, Jan-Christian; Bogner, Johannes R; Müller, Markus; Esser, Stefan; Schleicher, Alisa; Jensen, Björn; Stoehr, Albrecht; Behrens, Georg; Schultze, Alexander; Siehl, Jan; Thoden, Jan; Taylor, Ninon; Hoffmann, Christian

    2018-05-01

    Outcome of HIV-infected patients with AIDS-related lymphomas has improved during recent years. However, data on incidence, risk factors, and outcome of relapses in AIDS-related lymphomas after achieving complete remission are still limited. This prospective observational multicenter study includes HIV-infected patients with biopsy- or cytology-proven malignant lymphomas since 2005. Data on HIV infection and lymphoma characteristics, treatment and outcome were recorded. For this analysis, AIDS-related lymphomas patients in complete remission were analyzed in terms of their relapse- free survival and potential risk factors for relapses. In total, 254 of 399 (63.7%) patients with AIDS-related lymphomas reached a complete remission with their first-line chemotherapy. After a median follow up of 4.6 years, 5-year overall survival of the 254 patients was 87.8% (Standard Error 3.1%). Twenty-nine patients relapsed (11.4%). Several factors were independently associated with a higher relapse rate, including an unclassifiable histology, a stage III or IV according to the Ann Arbor Staging System, no concomitant combined antiretroviral therapy during chemotherapy and R-CHOP-based compared to more intensive chemotherapy regimens in Burkitt lymphomas. In conclusion, complete remission and relapse rates observed in our study are similar to those reported in HIV-negative non-Hodgkin lymphomas. These data provide further evidence for the use of concomitant combined antiretroviral therapy during chemotherapy and a benefit from more intensive chemotherapy regimens in Burkitt lymphomas. Modifications to the chemotherapy regimen appear to have only a limited impact on relapse rate. Copyright © 2018 Ferrata Storti Foundation.

  19. Axl acts as a tumor suppressor by regulating LIGHT expression in T lymphoma

    Science.gov (United States)

    Young, Kon-Ji; Park, A-Reum; Choi, Ha-Rim; Lee, Hwa-Youn; Kim, Su-Man; Chung, Byung Yeoup; Park, Chul-Hong; Choi, Hyo Jin; Ko, Young-Hyeh; Bai, Hyoung-Woo; Kang, Hyung-Sik

    2017-01-01

    Axl is an oncogenic receptor tyrosine kinase that plays a role in many cancers. LIGHT (Lymphotoxin-related inducible ligand that competes for glycoprotein D binding to herpesvirus entry mediator on T cells) is a ligand that induces robust anti-tumor immunity by enhancing the recruitment and activation of effector immune cells at tumor sites. We observed that mouse EL4 and human Jurkat T lymphoma cells that stably overexpressed Axl also showed high expression of LIGHT. When Jurkat-Axl cells were treated with Gas6, a ligand for Axl, LIGHT expression was upregulated through activation of the PI3K/AKT signaling pathway and transcriptional induction by Sp1. The lytic activity of cytotoxic T lymphocytes and natural killer cells was enhanced by EL4-Axl cells. In addition, tumor volume and growth were markedly reduced due to enhanced apoptotic cell death in EL4-Axl tumor-bearing mice as compared to control mice. We also observed upregulated expression of CCL5 and its receptor, CCR5, and enhanced intratumoral infiltration of cytotoxic T lymphocytes and natural killer cells in EL4-Axl-bearing mice as compared to mock controls. These data strongly suggested that Axl exerts novel tumor suppressor effects by inducing upregulation of LIGHT in the tumor microenvironment of T lymphoma. PMID:28423548

  20. The Oak Ridge Polycystic Kidney mouse: modeling ciliopathies of mice and men.

    Energy Technology Data Exchange (ETDEWEB)

    Lehman, J M [University of Alabama, Birmingham; Michaud III, Edward J [ORNL; Schoeb, T [University of Alabama, Birmingham; Aydin Son, Yesim [University of Tennessee, Knoxville (UTK); Miller, M [University of Alabama, Birmingham; Yoder, Bradley [University of Alabama, Birmingham

    2008-08-01

    The Oak Ridge Polycystic Kidney (ORPK) mouse was described nearly 14 years ago as a model for human recessive polycystic kidney disease. The ORPK mouse arose through integration of a transgene into an intron of the Ift88 gene resulting in a hypomorphic allele (Ift88Tg737Rpw). The Ift88Tg737Rpw mutation impairs intraflagellar transport (IFT), a process required for assembly of motile and immotile cilia. Historically, the primary immotile cilium was thought to have minimal importance for human health; however, a rapidly expanding number of human disorders have now been attributed to ciliary defects. Importantly, many of these phenotypes are present and can be analyzed using the ORPK mouse. In this review, we highlight the research conducted using the OPRK mouse and the phenotypes shared with human cilia disorders. Furthermore, we describe an additional follicular dysplasia phenotype in the ORPK mouse, which alongside the ectodermal dysplasias seen in human Ellis-van Creveld and Sensenbrenner's syndromes, suggests an unappreciated role for primary cilia in the skin and hair follicle.

  1. Use of a conformational switching aptamer for rapid and specific ex vivo identification of central nervous system lymphoma in a xenograft model

    Science.gov (United States)

    Georges, Joseph F.; Liu, Xiaowei; Eschbacher, Jennifer; Nichols, Joshua; Mooney, Michael A.; Joy, Anna; Spetzler, Robert F.; Feuerstein, Burt G.; Anderson, Trent; Preul, Mark C.; Yan, Hao; Nakaji, Peter

    2018-02-01

    Improved tools for providing specific intraoperative diagnoses could improve patient care. In neurosurgery, intraoperatively differentiating non-operative lesions can be challenging, often necessitating immunohistochemical (IHC) procedures which require up to 24-48 hours. Here, we evaluate the feasibility of generating rapid ex vivo specific labeling using a novel lymphoma-specific fluorescent switchable aptamer. Our B-cell lymphoma-specific switchable aptamer produced only low-level fluorescence in its unbound conformation and generated an 8-fold increase in fluorescence once bound to its target on CD20-positive lymphoma cells. The aptamer demonstrated strong binding to B-cell lymphoma cells within 10 minutes of incubation. We applied the switchable aptamer to ex vivo xenograft tissue harboring B-cell lymphoma and astrocytoma, and within one hour specific visual identification of lymphoma was routinely possible. In this proof-of-concept study in human cell culture and orthotopic xenografts, we conclude that a fluorescent switchable aptamer can provide rapid and specific labeling of B-cell lymphoma, and that developing aptamer-based labeling approaches could simplify tissue staining and drastically reduce time to histopathological diagnoses compared with IHC-based methods. We propose that switchable aptamers could enhance expeditious, accurate intraoperative decision-making.

  2. USING OF MOUSE MODEL TO ANALYZE IMMUNE RESPONSE TO INFECTIOUS PATHOGENS BY THE METHODS OF CLASSICAL GENETICS

    Directory of Open Access Journals (Sweden)

    A. Poltorak

    2011-01-01

    Full Text Available Abstract. Identification and studying of numerous functions of all genes of the human beings is one of the main objects of modern biological science. Due to high level of homology between mouse and human genomes the important role to reach above mentioned goal belongs to the mouse model which using in the classical genetics increase in connection with appearance of different inbred mouse lines. For instance, the differences in immune response to infectious pathogens in various mouse lines were used many times to determine immunologically competent genes. That is why the contribution of mouse model in understanding of the mechanisms of immune response to infectious pathogens is difficult to overestimate. In the current review some of the most successful and well known examples of mouse using in studies of anti-infectious response are described.

  3. Cholinergic anti-inflammatory pathway in the non-obese diabetic mouse model

    NARCIS (Netherlands)

    Koopman, F. A.; Vosters, J. L.; Roescher, N.; Broekstra, N.; Tak, P. P.; Vervoordeldonk, M. J.

    2015-01-01

    Activation of the cholinergic anti-inflammatory pathway (CAP) has been shown to reduce inflammation in animal models, while abrogation of the pathway increases inflammation. We investigated whether modulation of CAP influences inflammation in the non-obese diabetic (NOD) mouse model for Sjögren's

  4. Tumor microvessel density–associated mast cells in canine nodal lymphoma

    Science.gov (United States)

    Mann, Elizabeth; Whittington, Lisa

    2014-01-01

    Objective: Mast cells are associated in angiogenesis in various human and animal neoplasms. However, association of mast cells with tumor microvessel density in canine lymphoma was not previously documented. The objective of the study is to determine if mast cells are increased in canine nodal lymphomas and to evaluate their correlation with tumor microvessel density and grading of lymphomas. Methods: Nodal lymphomas from 33 dogs were studied and compared with nonneoplastic lymph nodes from 6 dogs as control. Mast cell count was made on Toluidine blue stained sections. Immunohistochemistry using antibody against Factor VIII was employed to visualize and determine microvessel density. Results: The mast cell count in lymphoma (2.95 ± 2.4) was significantly higher (p < 0.05) than that in the control (0.83 ± 0.3) and was positively correlated with tumor microvessel density (r = 0.44, p = 0.009). Significant difference was not observed in mast cell count and tumor microvessel density among different gradings of lymphomas. Conclusions: Mast cells are associated with tumor microvessel density in canine nodal lymphoma with no significant difference among gradings of lymphomas. Mast cells may play an important role in development of canine nodal lymphomas. Further detailed investigation on the role of mast cells as important part of tumor microenvironment in canine nodal lymphomas is recommended. PMID:26770752

  5. Tumor microvessel density–associated mast cells in canine nodal lymphoma

    Directory of Open Access Journals (Sweden)

    Moges Woldemeskel

    2014-11-01

    Full Text Available Objective: Mast cells are associated in angiogenesis in various human and animal neoplasms. However, association of mast cells with tumor microvessel density in canine lymphoma was not previously documented. The objective of the study is to determine if mast cells are increased in canine nodal lymphomas and to evaluate their correlation with tumor microvessel density and grading of lymphomas. Methods: Nodal lymphomas from 33 dogs were studied and compared with nonneoplastic lymph nodes from 6 dogs as control. Mast cell count was made on Toluidine blue stained sections. Immunohistochemistry using antibody against Factor VIII was employed to visualize and determine microvessel density. Results: The mast cell count in lymphoma (2.95 ± 2.4 was significantly higher (p < 0.05 than that in the control (0.83 ± 0.3 and was positively correlated with tumor microvessel density (r = 0.44, p = 0.009. Significant difference was not observed in mast cell count and tumor microvessel density among different gradings of lymphomas. Conclusions: Mast cells are associated with tumor microvessel density in canine nodal lymphoma with no significant difference among gradings of lymphomas. Mast cells may play an important role in development of canine nodal lymphomas. Further detailed investigation on the role of mast cells as important part of tumor microenvironment in canine nodal lymphomas is recommended.

  6. Primary colorectal lymphoma: spectrum of imaging findings with pathologic correlation

    International Nuclear Information System (INIS)

    Lee, Hyun Ju; Han, Joon Koo; Kim, Tae Kyoung; Kim, Young Hoon; Kim, Ah Young; Kim, Kyoung Won; Choi, Ja Young; Choi, Byung Ihn

    2002-01-01

    Primary colorectal lymphoma is a very uncommon disease; therefore, it has received little attention in the radiology literature. Moreover, imaging features of newly described pathologic subtypes have not been reported such as low-grade B-cell lymphoma arising from mucosa-associated lymphoid tissue and peripheral T-cell lymphoma that involves colorectal area. We retrospectively reviewed double-contrast barium enema and CT scans in the patients with primary colorectal lymphoma. In this article the radiologic appearances of primary colorectal lymphoma are categorized into focal lesion and diffuse lesion. Focal lesion includes polypoid mass, circumferential infiltration with smooth mucosal surface, circumferential infiltration with extensive ulceration, cavitary mass, mucosal nodularity, and mucosal fold thickening. Diffuse lesion includes diffuse ulcerative lesion and diffuse nodular lesion. Peripheral T-cell lymphomas that involve the colon manifested as either a diffuse or focal segmental lesion and showed extensive mucosal ulceration. These findings are similar to those of Crohn's disease or tuberculous colitis and are different from those of previously reported colorectal lymphoma. Low-grade B-cell lymphoma arising from mucosa-associated lymphoid tissue manifest as multiple mucosal nodularity. The imaging features of primary colorectal lymphoma are quite variable and overlap with other colonic pathology; however, it is important for radiologists to know the imaging features of primary colorectal lymphoma with their pathologic correlation. (orig.)

  7. Extracts of Crinum latifolium inhibit the cell viability of mouse lymphoma cell line EL4 and induce activation of anti-tumour activity of macrophages in vitro.

    Science.gov (United States)

    Nguyen, Hoang-Yen T; Vo, Bach-Hue T; Nguyen, Lac-Thuy H; Bernad, Jose; Alaeddine, Mohamad; Coste, Agnes; Reybier, Karine; Pipy, Bernard; Nepveu, Françoise

    2013-08-26

    active in any of the models investigated. Our results indicate that CL extracts and alkaloid fraction (but not pure 6-hydroxycrinamidine) inhibit the proliferation of lymphoma cells in multiple pathways. Our results are in accordance with traditional usage and encourage further studies and in vivo assays. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. CT findings in primary pulmonary lymphomas

    International Nuclear Information System (INIS)

    Cardinale, Luciano; Allasia, Marco; Cataldi, Aldo; Ferraris, Fabrizio; Fava, Cesare; Parvis, Guido

    2005-01-01

    Purpose. To describe the CT findings of pathologically confirmed primary pulmonary lymphomas. Materials and methods. The CT examinations of 11 patients with pathologically proven primary pulmonary lymphoma (9 BALT lymphomas and 2 non-BALT lymphomas) were retrospectively reviewed by three radiologists. Evaluated findings included morphology (consolidation, mass, nodule), number and distribution of lesions. Other CT findings such as air bronchogram, lymphadenopathy atelectasis and pleural effusion were also assessed. Results. Pulmonary lesions were depicted as air-space consolidation (pneumonia-like) in 5 patients (45%), tumour-like rounded opacity in 4 (36%), and nodules in 4 (36%). Multiple and bilateral long lesions were seen in 3 patients (27%). Air bronchogram was present in 7 patients (63%), lymphadenopathy in 3 (27%), atelectasis in 4 (36%) and pleural effusion in only 1 (9%). Conclusions. Our results agree with previous studies regarding lesion patterns and their relative frequency. A smaller number of nodules and of multiple lesions were found compared with some previous studies. The most frequent pattern was airspace consolidation [it

  9. Emerging diagnostic tests for vitreoretinal lymphoma.

    Science.gov (United States)

    Dawson, Abby C; Williams, Keryn A; Appukuttan, Binoy; Smith, Justine R

    2018-04-19

    Vitreoretinal lymphoma, which most commonly is diffuse large B cell non-Hodgkin in type, is a rare cancer with high morbidity and high mortality. Making a tissue diagnosis of vitreoretinal lymphoma is a major challenge for clinicians due to biological and technical factors. Yet, the delay in start of treatment may have vision- and life- threatening consequences, and there is considerable interest in the application of molecular assays to improve the accuracy of the diagnostic process: detection of a clonal immunoglobulin heavy chain rearrangements in lymphoma cells by polymerase chain reaction; measurement of vitreous or aqueous interleukin-10 protein levels in ocular fluids; and identification of mutations in the myeloid differentiation primary response gene 88 in tumour cells. In this article, we review the historical development and current application of each of these molecular methods. We also discuss future opportunities for the molecular diagnosis of vitreoretinal lymphoma through next generation sequencing technologies. This article is protected by copyright. All rights reserved.

  10. Medicinal therapy of malignant lymphomas

    International Nuclear Information System (INIS)

    Aul, C.; Schroeder, M.; Giagounidis, A.

    2002-01-01

    Chemotherapy represents the most important therapeutic option in malignant lymphomas. Low to intermediate risk Hodgkin's disease is treated by a combination of chemotherapy and radiation. The new chemotherapy protocol BEACOPP has improved the outcome of advanced stages in comparison with the internationally accepted standard protocol COPP/ABVD. Dependent on the initial staging, cure rates between 50 and 95% can be achieved. Indolent non-Hodgkin's lymphomas usually present in advanced stages of disease. Chemotherapy in these cases has palliative character and aims at improving patients'quality of life and at avoiding complications due to the disease. In aggressive and very aggressive non-Hodgkin's lymphoma chemotherapy is curative and must be initiated immediately irrespective of the staging results. The efficacy of the standard protocol CHOP (cyclophosphamide,doxorubicin, vincristine and prednisone), that was established in the 1970s, has recently been improved by shortening of the therapy interval (CHOP-14 vs.CHOP-21),addition of etoposide (CHOEP) and combination with the monoclonal antibody rituximab (R-CHOP). The value of high dose chemotherapy with stem cell transplantation has been shown unequivocally only for aggressive non-Hodgkin lymphoma and relapsed Hodgkin's disease responsive to chemotherapy. The therapeutic strategy of malignant lymphomas is likely to be improved within the next years due to the introduction of novel cytostatic agents, the broadening application of monoclonal antibodies,upcoming new transplantation procedures and the development of substances with molecular targets.To rapidly increase our current knowledge on the topic it is mandatory to include patients into the large national and international multicenter studies. (orig.) [de

  11. Classical Hodgkin's lymphoma: the Lymphoma Study Association guidelines for relapsed and refractory adult patients eligible for transplant.

    Science.gov (United States)

    Van Den Neste, Eric; Casasnovas, Olivier; André, Marc; Touati, Mohamed; Senecal, Delphine; Edeline, Véronique; Stamatoullas, Aspasia; Fornecker, Luc; Deau, Bénédicte; Gastinne, Thomas; Reman, Oumédaly; Gaillard, Isabelle; Borel, Cécile; Brice, Pauline; Fermé, Christophe

    2013-08-01

    The Hodgkin's Lymphoma Committee of the Lymphoma Study Association (LYSA) gathered in 2012 to prepare guidelines on the management of transplant-eligible patients with relapsing or refractory Hodgkin's lymphoma. The working group is made up of a multidisciplinary panel of experts with a significant background in Hodgkin's lymphoma. Each member of the panel of experts provided an interpretation of the evidence and a systematic approach to obtain consensus was used. Grades of recommendation were not required since levels of evidence are mainly based on phase II trials or standard practice. Data arising from randomized trials are emphasized. The final version was endorsed by the scientific council of the LYSA. The expert panel recommends a risk-adapted strategy (conventional treatment, or single/double transplantation and/or radiotherapy) based on three risk factors at progression (primary refractory disease, remission duration < 1 year, stage III/IV), and an early evaluation of salvage chemosensitivity, including (18)fluorodeoxy glucose-positron emission tomography interpreted according to the Deauville scoring system. Most relapsed or refractory Hodgkin's lymphoma patients chemosensitive to salvage should receive high-dose therapy and autologous stem-cell transplantation as standard. Efforts should be made to increase the proportion of chemosensitive patients by alternating non-cross-resistant chemotherapy lines or exploring the role of novel drugs.

  12. Development of a unilaterally-lesioned 6-OHDA mouse model of Parkinson's disease.

    Science.gov (United States)

    Thiele, Sherri L; Warre, Ruth; Nash, Joanne E

    2012-02-14

    The unilaterally lesioned 6-hyroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease (PD) has proved to be invaluable in advancing our understanding of the mechanisms underlying parkinsonian symptoms, since it recapitulates the changes in basal ganglia circuitry and pharmacology observed in parkinsonian patients(1-4). However, the precise cellular and molecular changes occurring at cortico-striatal synapses of the output pathways within the striatum, which is the major input region of the basal ganglia remain elusive, and this is believed to be site where pathological abnormalities underlying parkinsonian symptoms arise(3,5). In PD, understanding the mechanisms underlying changes in basal ganglia circuitry following degeneration of the nigro-striatal pathway has been greatly advanced by the development of bacterial artificial chromosome (BAC) mice over-expressing green fluorescent proteins driven by promoters specific for the two striatal output pathways (direct pathway: eGFP-D1; indirect pathway: eGFP-D2 and eGFP-A2a)(8), allowing them to be studied in isolation. For example, recent studies have suggested that there are pathological changes in synaptic plasticity in parkinsonian mice(9,10). However, these studies utilised juvenile mice and acute models of parkinsonism. It is unclear whether the changes described in adult rats with stable 6-OHDA lesions also occur in these models. Other groups have attempted to generate a stable unilaterally-lesioned 6-OHDA adult mouse model of PD by lesioning the medial forebrain bundle (MFB), unfortunately, the mortality rate in this study was extremely high, with only 14% surviving the surgery for 21 days or longer(11). More recent studies have generated intra-nigral lesions with both a low mortality rate >80% loss of dopaminergic neurons, however expression of L-DOPA induced dyskinesia(11,12,13,14) was variable in these studies. Another well established mouse model of PD is the MPTP-lesioned mouse(15). Whilst this

  13. Radiotherapy in non-Hodgkin lymphomas

    International Nuclear Information System (INIS)

    Faria, S.L.

    1992-01-01

    The treatment of non-Hodgkin lymphomas (NHL) is discussed. The use of radiotherapy, chemotherapy or both in a combined therapy is studied considering several aspects as age of the patients (adults vs children), size and extension of the lymphoma, stage of the disease. It is mentioned that more advanced cases and those with more aggressive histology need combined modality treatments or even just chemotherapy. (M.A.C.)

  14. Immune Thrombocytopenia in a Child with T Cell Lymphoblastic Lymphoma

    Directory of Open Access Journals (Sweden)

    Kayo Tokeji

    2016-01-01

    Full Text Available We describe the case of a 13-year-old boy who presented with persistent thrombocytopenia during maintenance chemotherapy with mercaptopurine and methotrexate for T cell lymphoblastic lymphoma. He was diagnosed with immune thrombocytopenia (ITP after thorough investigations for the relapse of lymphoma and was successfully treated with immunoglobulin and steroids. ITP is known to be associated with chronic lymphocytic leukemia, Hodgkin lymphoma, and various types of non-Hodgkin lymphoma but rarely with T cell non-Hodgkin lymphoma or in children. Diagnosis of ITP with lymphoma is challenging due to the many factors affecting platelet counts, and ITP often complicates the diagnosis or treatment course of lymphoma. The underlying mechanism of ITP with NHL is still unclear. Drug-induced immunomodulation with a reduction of regulatory T cells might have contributed to the development of ITP in our case.

  15. Incidence, determinants and the transient impact of cancer treatments on venous thromboembolism risk among lymphoma patients in Denmark

    DEFF Research Database (Denmark)

    Lund, Jennifer L; Østgård, Lene Sofie; Prandoni, Paolo

    2015-01-01

    BACKGROUND: Valid estimation of the incidence and risk factors for venous thromboembolism (VTE) among lymphoma patients has been limited by small studies focused on selected lymphoma subtypes and failure to account for death as a competing risk. Using a nationwide cohort of Danish lymphoma patients...... logistic regression models and adjusted odds ratios (aORs). RESULTS: VTE IRs were >40/1000person-years within 180days post-diagnosis, decreasing to 8/1000person-years in year two. VTE risk was 2.9% and 3.5% at 1 and 2years, respectively. Lymphoma subtype, central nervous system involvement, and elevated...... lactate dehydrogenase were associated with VTE risk. Central venous catheter use increased the transient odds of VTE (aOR=6.7 (1.2, 28.1)). CONCLUSIONS: We report a lower VTE incidence among lymphoma patients compared with prior studies. Lymphoma aggressiveness was the main driver of baseline VTE risk...

  16. Lymphomas of the gastro-intestinal tract - Pathophysiology, pathology, and differential diagnosis

    Directory of Open Access Journals (Sweden)

    Diana M Cardona

    2012-01-01

    Full Text Available The gastrointestinal tract (GIT is the most commonly involved site of extranodal lymphomas. The close association between chronic inflammation and specific GIT lymphomas not only provide interesting insights into the pathobiology of lymphomas but also poses unique diagnostic challenges. A clear understanding of marginal zone and mucosa associated lymphoid tissue (MALT in health and disease is helpful to place GIT lymphomas in proper context. A wide variety of lymphomas besides MALT lymphomas occur in various parts of the GIT. The characteristic pathological, immunophenotypic, and genetic features of different GIT lymphomas categorized according to World Health Organization (WHO classification are presented. The epidemiological, clinical, and pathological features of lymphomas occurring in each part of the GIT are summarized and the key points regarding lymphomas at each site are emphasized. A tabular summary of the important differential diagnostic considerations at each site is given and suggestions for a minimal diagnostic work up are provided.

  17. A New Mouse Model That Spontaneously Develops Chronic Liver Inflammation and Fibrosis.

    Directory of Open Access Journals (Sweden)

    Nina Fransén-Pettersson

    Full Text Available Here we characterize a new animal model that spontaneously develops chronic inflammation and fibrosis in multiple organs, the non-obese diabetic inflammation and fibrosis (N-IF mouse. In the liver, the N-IF mouse displays inflammation and fibrosis particularly evident around portal tracts and central veins and accompanied with evidence of abnormal intrahepatic bile ducts. The extensive cellular infiltration consists mainly of macrophages, granulocytes, particularly eosinophils, and mast cells. This inflammatory syndrome is mediated by a transgenic population of natural killer T cells (NKT induced in an immunodeficient NOD genetic background. The disease is transferrable to immunodeficient recipients, while polyclonal T cells from unaffected syngeneic donors can inhibit the disease phenotype. Because of the fibrotic component, early on-set, spontaneous nature and reproducibility, this novel mouse model provides a unique tool to gain further insight into the underlying mechanisms mediating transformation of chronic inflammation into fibrosis and to evaluate intervention protocols for treating conditions of fibrotic disorders.

  18. Hodgkin's Lymphoma

    Science.gov (United States)

    ... People who have had illnesses caused by the Epstein-Barr virus, such as infectious mononucleosis, are more likely to develop Hodgkin's lymphoma than are people who haven't had Epstein-Barr infections. By Mayo Clinic Staff . Mayo Clinic Footer ...

  19. Ovarian lymphoma

    International Nuclear Information System (INIS)

    Bonet Fonseca, Ivan; Diaz Anaya, Amnia; Francis, Tabu

    2012-01-01

    50 % of pediatric oncologic pathology corresponds to mass or solid tumors, reaching about 20 % of total abdomen. The tumors that most frequently occur in the abdomen are nephroblastoma or Wilms tumor, Burkitts lymphoma, neuroblastoma, and ovarian germ cell tumors

  20. Adult high-grade B-cell lymphoma with Burkitt lymphoma signature: genomic features and potential therapeutic targets.

    Science.gov (United States)

    Bouska, Alyssa; Bi, Chengfeng; Lone, Waseem; Zhang, Weiwei; Kedwaii, Ambreen; Heavican, Tayla; Lachel, Cynthia M; Yu, Jiayu; Ferro, Roberto; Eldorghamy, Nanees; Greiner, Timothy C; Vose, Julie; Weisenburger, Dennis D; Gascoyne, Randy D; Rosenwald, Andreas; Ott, German; Campo, Elias; Rimsza, Lisa M; Jaffe, Elaine S; Braziel, Rita M; Siebert, Reiner; Miles, Rodney R; Dave, Sandeep; Reddy, Anupama; Delabie, Jan; Staudt, Louis M; Song, Joo Y; McKeithan, Timothy W; Fu, Kai; Green, Michael; Chan, Wing C; Iqbal, Javeed

    2017-10-19

    The adult high-grade B-cell lymphomas sharing molecular features with Burkitt lymphoma (BL) are highly aggressive lymphomas with poor clinical outcome. High-resolution structural and functional genomic analysis of adult Burkitt lymphoma (BL) and high-grade B-cell lymphoma with BL gene signature (adult-molecularly defined BL [mBL]) revealed the MYC-ARF-p53 axis as the primary deregulated pathway. Adult-mBL had either unique or more frequent genomic aberrations (del13q14, del17p, gain8q24, and gain18q21) compared with pediatric-mBL, but shared commonly mutated genes. Mutations in genes promoting the tonic B-cell receptor (BCR)→PI3K pathway ( TCF3 and ID3 ) did not differ by age, whereas effectors of chronic BCR→NF-κB signaling were associated with adult-mBL. A subset of adult-mBL had BCL2 translocation and mutation and elevated BCL2 mRNA and protein expression, but had a mutation profile similar to mBL. These double-hit lymphomas may have arisen from a tumor precursor that acquired both BCL2 and MYC translocations and/or KMT2D ( MLL2 ) mutation. Gain/amplification of MIR17HG and its paralogue loci was observed in 50% of adult-mBL. In vitro studies suggested miR-17∼92 's role in constitutive activation of BCR signaling and sensitivity to ibrutinib. Overall integrative analysis identified an interrelated gene network affected by copy number and mutation, leading to disruption of the p53 pathway and the BCR→PI3K or NF-κB activation, which can be further exploited in vivo by small-molecule inhibitors for effective therapy in adult-mBL.

  1. Dmdmdx/Largemyd: a new mouse model of neuromuscular diseases useful for studying physiopathological mechanisms and testing therapies

    Directory of Open Access Journals (Sweden)

    Poliana C. M. Martins

    2013-09-01

    Although muscular dystrophies are among the most common human genetic disorders, there are few treatment options available. Animal models have become increasingly important for testing new therapies prior to entering human clinical trials. The Dmdmdx mouse is the most widely used animal model for Duchenne muscular dystrophy (DMD, presenting the same molecular and protein defect as seen in humans with the disease. However, this mouse is not useful for clinical trials because of its very mild phenotype. The mouse model for congenital myodystrophy type 1D, Largemyd, harbors a mutation in the glycosyltransferase Large gene and displays a severe phenotype. To help elucidate the role of the proteins dystrophin and LARGE in the organization of the dystrophin-glycoprotein complex in muscle sarcolemma, we generated double-mutant mice for the dystrophin and LARGE proteins. The new Dmdmdx/Largemyd mouse model is viable and shows a severe phenotype that is associated with the lack of dystrophin in muscle. We tested the usefulness of our new mouse model for cell therapy by systemically injecting them with normal murine mesenchymal adipose stem cells (mASCs. We verified that the mASCs were hosted in the dystrophic muscle. The new mouse model has proven to be very useful for the study of several other therapies, because injected cells can be screened both through DNA and protein analysis. Study of its substantial muscle weakness will also be very informative in the evaluation of functional benefits of these therapies.

  2. Towards a mouse model of depression : a psychoneuroendocrine approach

    NARCIS (Netherlands)

    Dalm, Sergiu

    2012-01-01

    Chronic stress is considered a vulnerability factor for depression. A key symptom is anhedonia; a reduced response to positive stimuli. Drugs are effective for only 20-40% of the patients and new drugs are urgently needed. The objective of the research was to develop a mouse model of depression that

  3. Sparse Statistical Deformation Model for the Analysis of Craniofacial Malformations in the Crouzon Mouse

    DEFF Research Database (Denmark)

    Ólafsdóttir, Hildur; Hansen, Michael Sass; Sjöstrand, Karl

    2007-01-01

    Crouzon syndrome is characterised by the premature fusion of cranial sutures. Recently the first genetic Crouzon mouse model was generated. In this study, Micro CT skull scannings of wild-type mice and Crouzon mice were investigated. Using nonrigid registration, a wild-type mouse atlas was built...

  4. AIDS-Related Lymphoma Treatment (PDQ®)—Health Professional Version

    Science.gov (United States)

    AIDS-related lymphoma presents and is treated differently compared to lymphoma in non-HIV patients. Treatments include chemotherapy, radiation therapy, high-dose chemotherapy with stem cell transplant, and targeted therapy. Get detailed information about HIV-related lymphoma in this summary for clinicians.

  5. Histologic progression in non-hodgkin's lymphoma

    International Nuclear Information System (INIS)

    Hubbard, S.M.; Chabner, B.A.; DeVita, V.T. Jr.; Simon, R.; Berard, C.W.; Jones, R.B.; Garvin, A.J.; Canellos, G.P.; Osborne, C.K.; Young, R.C.

    1982-01-01

    The clinical course and biopsy specimens from 515 consecutive non-Hodgkin's lymphoma patients was evaluated retrospectively in an attempt to determine the clinical importance of documented changes in histology over time. Two-hundred and five of these patients has an initial diagnosis of nodular lymphoma and were reviewed for this anaysis. Sixty-three underwent a repeat biopsy greater than 6 mo after initial diagnosis. In 23 patients, these repeat biopsies revealed a change in histology to a diffuse pattern and/or a change to a larger ''histiocytic'' cell type, while repeat biopsies for the other 40 (63%) disclosd persistence of a nodular pattern and no clear change in basic cell type. Progression from nodular lymphoma to diffuse histiocytic, mixed, or undifferentiated types of lymphomas of Rappaport was found in repeate biopsies obtained from 19 patients (30%). Prognosis for survival following a biopsy that demonstrated histologic change was related to the histology demonstrated at the most recent biopsy and to the response to subsequent drug treatment. Survival following repeat biopsy for these 19 patients was significantly shorter than for the 40 patients whose histology remained nodular (p < 0.001). However, attainment of a complete remission with intensive combination chemotherapy was associated with prolonged survival in eight patients and prolonged disease-free survival in one patient. Since prior treatment may compromise the ability to achieve a complete response to chemotherapy in patients with nodular lymphoma who develop an aggressive diffuse histology, the likelihood of histologic progression must be considered in the design of future clinical trials in nodular lymphoma. Histologic progression does not preclude attainment of a complete response to intensive chemotherapy

  6. Everolimus and Lenalidomide in Treating Patients With Relapsed or Refractory Non-Hodgkin or Hodgkin Lymphoma

    Science.gov (United States)

    2018-02-07

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Splenic Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia

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

    Science.gov (United States)

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

    2005-07-01

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

  8. Mouse neuroblastoma cell based model and the effect of epileptic events on calcium oscillations and neural spikes

    Science.gov (United States)

    Kim, Suhwan; Baek, Juyeong; Jung, Unsang; Lee, Sangwon; Jung, Woonggyu; Kim, Jeehyun; Kang, Shinwon

    2013-05-01

    Recently, Mouse neuroblastoma cells are considered as an attractive model for the study of human neurological and prion diseases, and intensively used as a model system in different areas. Among those areas, differentiation of neuro2a (N2A) cells, receptor mediated ion current, and glutamate induced physiological response are actively investigated. The reason for the interest to mouse neuroblastoma N2A cells is that they have a fast growing rate than other cells in neural origin with a few another advantages. This study evaluated the calcium oscillations and neural spikes recording of mouse neuroblastoma N2A cells in an epileptic condition. Based on our observation of neural spikes in mouse N2A cell with our proposed imaging modality, we report that mouse neuroblastoma N2A cells can be an important model related to epileptic activity studies. It is concluded that the mouse neuroblastoma N2A cells produce the epileptic spikes in vitro in the same way as produced by the neurons or the astrocytes. This evidence advocates the increased and strong level of neurotransmitters release by enhancement in free calcium using the 4-aminopyridine which causes the mouse neuroblastoma N2A cells to produce the epileptic spikes and calcium oscillation.

  9. [Effect of topical application of a recombinant adenovirus carrying promyelocytic leukemia gene in a psoriasis-like mouse model].

    Science.gov (United States)

    Wang, Qiongyu; Zhang, Aijun; Ma, Huiqun; Wang, Shijie; Ma, Yunyun; Zou, Xingwei; Li, Ruilian

    2013-03-01

    To investigate the effects of topical treatment with adenovirus-mediated promyelocytic leukemia gene (PML) gene in a psoriasis-like mouse model. The effect of adenovirus-mediated PML gene on the granular layer of mouse tail scale epidermis and epithelial mitosis were observed on longitudinal histological sections prepared from the tail skin and vaginal epithelium of the mice. Adenovirus-mediated PML gene significantly inhibited mitosis of mouse vaginal epithelial cells and promoted the formation of granular layer in mouse tail scale epidermis. The therapeutic effect of PML gene in the psoriasis-like mouse model may be associated with increased granular cells and suppressed epidemic cell proliferation.

  10. Combined exposure to X-irradiation followed by N-ethyl-N-nitrosourea treatment alters the frequency and spectrum of Ikaros point mutations in murine T-cell lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Kakinuma, Shizuko, E-mail: skakinum@nirs.go.jp [Radiobiology for Children' s Health Research Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Nishimura, Mayumi; Amasaki, Yoshiko; Takada, Mayumi; Yamauchi, Kazumi; Sudo, Satomi; Shang, Yi [Radiobiology for Children' s Health Research Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Doi, Kazutaka; Yoshinaga, Shinji [Regulatory Sciences Research Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Shimada, Yoshiya [Radiobiology for Children' s Health Research Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan)

    2012-09-01

    Ionizing radiation is a well-known carcinogen, but its potency may be influenced by other environmental carcinogens, which is of practical importance in the assessment of risk. Data are scarce, however, on the combined effect of radiation with other environmental carcinogens and the underlying mechanisms involved. We studied the mode and mechanism of the carcinogenic effect of radiation in combination with N-ethyl-N-nitrosourea (ENU) using doses approximately equal to the corresponding thresholds. B6C3F1 mice exposed to fractionated X-irradiation (Kaplan's method) followed by ENU developed T-cell lymphomas in a dose-dependent manner. Radiation doses above an apparent threshold acted synergistically with ENU to promote lymphoma development, whereas radiation doses below that threshold antagonized lymphoma development. Ikaros, which regulates the commitment and differentiation of lymphoid lineage cells, is a critical tumor suppressor gene frequently altered in both human and mouse lymphomas and shows distinct mutation spectra between X-ray- and ENU-induced lymphomas. In the synergistically induced lymphomas, we observed a low frequency of LOH and an inordinate increase of Ikaros base substitutions characteristic of ENU-indcued point mutations, G:C to A:T at non-CpG, A:T to G:C, G:C to T:A and A:T to T:A. This suggests that radiation doses above an apparent threshold activate the ENU mutagenic pathway. This is the first report on the carcinogenic mechanism elicited by combined exposure to carcinogens below and above threshold doses based on the mutation spectrum of the causative gene. These findings constitute a basis for assessing human cancer risk following exposure to multiple carcinogens.

  11. Fractalkine overexpression suppresses tau pathology in a mouse model of tauopathy.

    Science.gov (United States)

    Nash, Kevin R; Lee, Daniel C; Hunt, Jerry B; Morganti, Josh M; Selenica, Maj-Linda; Moran, Peter; Reid, Patrick; Brownlow, Milene; Guang-Yu Yang, Clement; Savalia, Miloni; Gemma, Carmelina; Bickford, Paula C; Gordon, Marcia N; Morgan, David

    2013-06-01

    Alzheimer's disease is characterized by amyloid plaques, neurofibrillary tangles, glial activation, and neurodegeneration. In mouse models, inflammatory activation of microglia accelerates tau pathology. The chemokine fractalkine serves as an endogenous neuronal modulator to quell microglial activation. Experiments with fractalkine receptor null mice suggest that fractalkine signaling diminishes tau pathology, but exacerbates amyloid pathology. Consistent with this outcome, we report here that soluble fractalkine overexpression using adeno-associated viral vectors significantly reduced tau pathology in the rTg4510 mouse model of tau deposition. Furthermore, this treatment reduced microglial activation and appeared to prevent neurodegeneration normally found in this model. However, in contrast to studies with fractalkine receptor null mice, parallel studies in an APP/PS1 model found no effect of increased fractalkine signaling on amyloid deposition. These data argue that agonism at fractalkine receptors might be an excellent target for therapeutic intervention in tauopathies, including those associated with amyloid deposition. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Treatment Option Overview (Adult Non-Hodgkin Lymphoma)

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... lymphoma may come back as indolent lymphoma. Treatment Option Overview Key Points There are different types of ...

  13. Parotid lymphomas - clinical and computed tomogrphic imaging ...

    African Journals Online (AJOL)

    Parotid lymphomas - clinical and computed tomogrphic imaging features. ... South African Journal of Surgery ... Lymphoma has a clinical presentation similar ... CT scanning is a useful adjunctive investigation to determine the site and extent of ...

  14. Construction of a mouse model of factor VIII deficiency by gene targeting

    Energy Technology Data Exchange (ETDEWEB)

    Bi, L.; Lawler, A.; Gearhart, J. [Univ. of Pennsylvania School of Medicine, Philadelphia, PA (United States)] [and others

    1994-09-01

    To develop a small animal model of hemophilia A for gene therapy experiments, we set out to construct a mouse model for factor VIII deficiency by gene targeting. First, we screened a mouse liver cDNA library using a human FVIII cDNA probe. We cloned a 2.6 Kb partial mouse factor VIII cDNA which extends from 800 base pairs of the 3{prime} end of exon 14 to the 5{prime} end of exon 26. A mouse genomic library made from strain 129 was then screened to obtain genomic fragments covering the exons desired for homologous recombination. Two genomic clones were obtained, and one covering exon 15 through 22 was used for gene targeting. To make gene targeting constructs, a 5.8 Kb genomic DNA fragment covering exons 15 to 19 of the mouse FVIII gene was subcloned, and the neo expression cassette was inserted into exons 16 and 17 separately by different strategies. These two constructs were named MFVIIIC-16 and MFVIIIC-17. The constructs were linearized and transfected into strain 129 mouse ES cells by electroporation. Factor VIII gene-knockout ES cell lines were selected by G-418 and screened by genomic Southern blots. Eight exon 16 targeted cell lines and five exon 17 targeted cell lines were obtained. Three cell lines from each construct were injected into blastocysts and surgically transferred into foster mothers. Multiple chimeric mice with 70-90% hair color derived from the ES-cell genotype were seen with both constructs. Germ line transmission of the ES-cell genotype has been obtained for the MFVIIIC-16 construct, and multiple hemophilia A carrier females have been identified. Factor VIII-deficient males will be conceived soon.

  15. Epigenetic regulation of CD44 in Hodgkin and non-Hodgkin lymphoma

    International Nuclear Information System (INIS)

    Eberth, Sonja; Schneider, Björn; Rosenwald, Andreas; Hartmann, Elena M; Romani, Julia; Zaborski, Margarete; Siebert, Reiner; Drexler, Hans G; Quentmeier, Hilmar

    2010-01-01

    Epigenetic inactivation of tumor suppressor genes (TSG) by promoter CpG island hypermethylation is a hallmark of cancer. To assay its extent in human lymphoma, methylation of 24 TSG was analyzed in lymphoma-derived cell lines as well as in patient samples. We screened for TSG methylation using methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) in 40 lymphoma-derived cell lines representing anaplastic large cell lymphoma, Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), Hodgkin lymphoma and mantle cell lymphoma (MCL) as well as in 50 primary lymphoma samples. The methylation status of differentially methylated CD44 was verified by methylation-specific PCR and bisulfite sequencing. Gene expression of CD44 and its reactivation by DNA demethylation was determined by quantitative real-time PCR and on the protein level by flow cytometry. Induction of apoptosis by anti-CD44 antibody was analyzed by annexin-V/PI staining and flow cytometry. On average 8 ± 2.8 of 24 TSG were methylated per lymphoma cell line and 2.4 ± 2 of 24 TSG in primary lymphomas, whereas 0/24 TSG were methylated in tonsils and blood mononuclear cells from healthy donors. Notably, we identified that CD44 was hypermethylated and transcriptionally silenced in all BL and most FL and DLBCL cell lines, but was usually unmethylated and expressed in MCL cell lines. Concordant results were obtained from primary lymphoma material: CD44 was not methylated in MCL patients (0/11) whereas CD44 was frequently hypermethylated in BL patients (18/29). In cell lines with CD44 hypermethylation, expression was re-inducible at mRNA and protein levels by treatment with the DNA demethylating agent 5-Aza-2'-deoxycytidine, confirming epigenetic regulation of CD44. CD44 ligation assays with a monoclonal anti-CD44 antibody showed that CD44 can mediate apoptosis in CD44 + lymphoma cells. CD44 hypermethylated, CD44 - lymphoma cell lines were consistently

  16. Clinicopathological and genomic analysis of double-hit follicular lymphoma: comparison with high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements.

    Science.gov (United States)

    Miyaoka, Masashi; Kikuti, Yara Y; Carreras, Joaquim; Ikoma, Haruka; Hiraiwa, Shinichiro; Ichiki, Akifumi; Kojima, Minoru; Ando, Kiyoshi; Yokose, Tomoyuki; Sakai, Rika; Hoshikawa, Masahiro; Tomita, Naoto; Miura, Ikuo; Takata, Katsuyoshi; Yoshino, Tadashi; Takizawa, Jun; Bea, Silvia; Campo, Elias; Nakamura, Naoya

    2018-02-01

    Most high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements are aggressive B-cell lymphomas. Occasional double-hit follicular lymphomas have been described but the clinicopathological features of these tumors are not well known. To clarify the characteristics of double-hit follicular lymphomas, we analyzed 10 cases of double-hit follicular lymphomas and 15 cases of high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements for clinicopathological and genome-wide copy-number alterations and copy-neutral loss-of-heterozygosity profiles. For double-hit follicular lymphomas, the median age was 67.5 years (range: 48-82 years). The female/male ratio was 2.3. Eight patients presented with advanced clinical stage. The median follow-up time was 20 months (range: 1-132 months). At the end of the follow-up, 8 patients were alive, 2 patients were dead including 1 patient with diffuse large B-cell lymphoma transformation. Rearrangements of MYC/BCL2, MYC/BCL6, and MYC/BCL2/BCL6 were seen in 8, 1, and 1 cases, respectively. The partner of MYC was IGH in 6 cases. There were no cases of histological grade 1, 4 cases of grade 2, 5 cases of grade 3a, and 1 case of grade 3b. Two cases of grade 3a exhibited immunoblast-like morphology. Immunohistochemistry demonstrated 9 cases with ≥50% MYC-positive cells. There was significant difference in MYC intensity (P=0.00004) and MIB-1 positivity (P=0.001) between double-hit follicular lymphomas and high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements. The genome profile of double-hit follicular lymphomas was comparable with conventional follicular lymphomas (GSE67385, n=198) with characteristic gains of 2p25.3-p11.1, 7p22.3-q36.3, 12q11-q24.33, and loss of 18q21.32-q23 (Phit follicular lymphomas had fewer copy-number alterations and minimal common region of gain at 2p16.1 (70%), locus also significant against conventional follicular lymphomas (P=0.0001). In summary, double-hit follicular

  17. Imaging of supradiaphragmatic manifestations of extranodal nonHodgkin's lymphoma

    International Nuclear Information System (INIS)

    Cohnen, M.; Saleh, A.; Engelbrecht, V.; Moedder, U.; Germing, U.

    2002-01-01

    Malignant lymphomas are differentiated into Hodgkin's and non-Hodgkin's-lymphoma (NHL). The following article discusses the imaging of extranodal NHL in supradiaphragmatic localizations. Lymphoma can affect nearly all tissues, and represent a rare entity as primary extranodal NHL. A secondary involvement of non-nodal tissue as consequence of a generalized lymphoproliferative disease is more common,and may be seen as well in HIV-positive patients defining AIDS. As extranodal lymphoma mimick the radiologic appearance of other malignant tumors, direct diagnosis without histologic analysis is often impossible. The article describes typical manifestations of lymphoma of the lungs, the head and neck area including the large glands, and rare localizations as the heart or the breast. (orig.) [de

  18. Primary conjunctival follicular lymphoma mimicking chronic conjunctivitis.

    Science.gov (United States)

    Labrador Velandia, S; García Lagarto, E; Saornil, M A; García Álvarez, C; Cuello, R; Diezhandino, P

    2016-02-01

    The case is presented of a 43 year-old male patient with chronic follicular conjunctivitis, negative bacterial serology, and refractory to local treatment. The incisional biopsy performed showed to be consistent with reactive lymphoid hyperplasia. A year later, a new incisional biopsy showed follicular lymphoma, with no systemic involvement, and he was treated with local radiotherapy. When a chronic follicular conjunctivitis is refractory to treatment, it is essential to perform an incisional biopsy to establish the histopathological diagnosis that can range from chronic inflammation, reactive lymphoid hyperplasia to lymphoma. Follicular lymphoma is rare among conjunctival lymphomas, and the staging is indispensable for the correct therapeutic approach. Copyright © 2014 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  19. Primary Vitreoretinal Lymphoma Masquerading as Refractory Retinitis

    Directory of Open Access Journals (Sweden)

    Ofira Zloto

    2015-10-01

    Full Text Available Purpose: To report a case of a patient with primary vitreoretinal lymphoma masquerading as retinitis. Methods: Retrospective review of the patient's clinical, histopathological and imaging records. Results: Cytopathology was negative for malignancy, and preliminary polymerase chain reaction results supported the diagnosis of varicella zoster virus retinitis. Therefore, the patient was treated with antiviral therapy. However, under this treatment, the retinitis progressed. As a result, primary vitreoretinal lymphoma was suspected, and empirical treatment with intravitreal methotrexate injections was started. Under this treatment, the ocular features improved. Five months after initial ocular presentation and ocular resolution, the patient presented with central nervous system lymphoma. Conclusion: This case should raise the awareness of the variable clinical presentations, the challenging diagnosis and treatment of primary vitreoretinal lymphoma. All cases should be continuously systemically evaluated.

  20. Riluzole does not improve lifespan or motor function in three ALS mouse models.

    Science.gov (United States)

    Hogg, Marion C; Halang, Luise; Woods, Ina; Coughlan, Karen S; Prehn, Jochen H M

    2017-12-08

    Riluzole is the most widespread therapeutic for treatment of the progressive degenerative disease amyotrophic lateral sclerosis (ALS). Riluzole gained FDA approval in 1995 before the development of ALS mouse models. We assessed riluzole in three transgenic ALS mouse models: the SOD1 G93A model, the TDP-43 A315T model, and the recently developed FUS (1-359) model. Age, sex and litter-matched mice were treated with riluzole (22 mg/kg) in drinking water or vehicle (DMSO) from symptom onset. Lifespan was assessed and motor function tests were carried out twice weekly to determine whether riluzole slowed disease progression. Riluzole treatment had no significant benefit on lifespan in any of the ALS mouse models tested. Riluzole had no significant impact on decline in motor performance in the FUS (1-359) and SOD1 G93A transgenic mice as assessed by Rotarod and stride length analysis. Riluzole is widely prescribed for ALS patients despite questions surrounding its efficacy. Our data suggest that if riluzole was identified as a therapeutic candidate today it would not progress past pre-clinical assessment. This raises questions about the standards used in pre-clinical assessment of therapeutic candidates for the treatment of ALS.

  1. Transformation of Follicular Lymphoma

    Science.gov (United States)

    Lossos, Izidore S.; Gascoyne, Randy D.

    2011-01-01

    Histological transformation of follicular lymphoma (FL) to a more aggressive non-Hodgkin's lymphomas is a pivotal event in the natural history of FL and is associated with poor outcome. While commonly observed in clinical practice and despite multiple studies designed to address its pathogenesis, the biology of this process represents an enigma. In this chapter we present a state of the art review summarizing the definition of histologic transformation, its incidence, pathogenesis, clinical manifestations, treatment and outcome. Furthermore, we specifically emphasize gaps in our knowledge that should be addressed in future studies. PMID:21658615

  2. Lymphoma of the Cervix

    Directory of Open Access Journals (Sweden)

    Juanita Parnis

    2012-01-01

    Full Text Available Primary non-Hodgkins lymphoma of the uterine cervix is a very rare diagnosis. A 54-year-old woman presented with a 3-month history of postmenopausal bleeding per vaginum. On examination, a friable, fungating lesion was seen on the cervix. Histology revealed a CD 20 positive high-grade non-Hodgkin’s diffuse large B cell lymphoma from cervical biopsies and endometrial curettage. She was diagnosed as stage IE after workup and subsequently treated with six cycles of R-CHOP chemotherapy followed by radiotherapy of the involved field.

  3. PET/CT for therapy response assessment in lymphoma

    DEFF Research Database (Denmark)

    Hutchings, Martin; Barrington, Sally F

    2009-01-01

    PET with (18)F-FDG is a standard staging procedure for most lymphoma subtypes. Performed during and after therapy for Hodgkin lymphoma (HL) and aggressive non-Hodgkin lymphoma (NHL), (18)F-FDG PET results have a high prognostic value and correlate with survival. (18)F-FDG PET has been incorporated...... into revised response criteria for aggressive lymphomas, and several ongoing trials are under way to investigate the value of treatment adaptation based on early (18)F-FDG PET results for HL and aggressive NHL. There is little evidence to support the use of (18)F-FDG PET for monitoring of the treatment...... of indolent lymphomas and for routine use in the surveillance setting. So that trial results can be compared and translated easily into clinical practice, uniform and evidence-based guidelines for the interpretation and reporting of response monitoring scans are warranted. Because it is still not proven...

  4. Differential Expression of Ccn4 and Other Genes Between Metastatic and Non-metastatic EL4 Mouse Lymphoma Cells.

    Science.gov (United States)

    Chahal, Manpreet S; Ku, H Teresa; Zhang, Zhihong; Legaspi, Christian M; Luo, Angela; Hopkins, Mandi M; Meier, Kathryn E

    Previous work characterized variants of the EL4 murine lymphoma cell line. Some are non-metastatic, and others metastatic, in syngenic mice. In addition, metastatic EL4 cells were stably transfected with phospholipase D2 (PLD2), which further enhanced metastasis. Microarray analyses of mRNA expression was performed for non-metastatic, metastatic, and PLD2-expressing metastatic EL4 cells. Many differences were observed between non-metastatic and metastatic cell lines. One of the most striking new findings was up-regulation of mRNA for the matricellular protein WNT1-inducible signaling pathway protein 1 (CCN4) in metastatic cells; increased protein expression was verified by immunoblotting and immunocytochemistry. Other differentially expressed genes included those for reproductive homeobox 5 (Rhox5; increased in metastatic) and cystatin 7 (Cst7; decreased in metastatic). Differences between PLD2-expressing and parental cell lines were limited but included the signaling proteins Ras guanyl releasing protein 1 (RGS18; increased with PLD2) and suppressor of cytokine signaling 2 (SOCS2; decreased with PLD2). The results provide insights into signaling pathways potentially involved in conferring metastatic ability on lymphoma cells. Copyright© 2016, International Institute of Anticancer Research (Dr. John G. Delinasios), All rights reserved.

  5. Fusion Protein Cytokine Therapy After Rituximab in Treating Patients With B-Cell Non-Hodgkin Lymphoma

    Science.gov (United States)

    2015-06-03

    Anaplastic Large Cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenstrom Macroglobulinemia

  6. Genetically engineered mouse models of craniopharyngioma: an opportunity for therapy development and understanding of tumor biology.

    Science.gov (United States)

    Apps, John Richard; Martinez-Barbera, Juan Pedro

    2017-05-01

    Adamantinomatous craniopharyngioma (ACP) is the commonest tumor of the sellar region in childhood. Two genetically engineered mouse models have been developed and are giving valuable insights into ACP biology. These models have identified novel pathways activated in tumors, revealed an important function of paracrine signalling and extended conventional theories about the role of organ-specific stem cells in tumorigenesis. In this review, we summarize these mouse models, what has been learnt, their limitations and open questions for future research. We then discussed how these mouse models may be used to test novel therapeutics against potentially targetable pathways recently identified in human ACP. © 2017 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.

  7. TNFRSF14 aberrations in follicular lymphoma increase clinically significant allogeneic T-cell responses.

    Science.gov (United States)

    Kotsiou, Eleni; Okosun, Jessica; Besley, Caroline; Iqbal, Sameena; Matthews, Janet; Fitzgibbon, Jude; Gribben, John G; Davies, Jeffrey K

    2016-07-07

    Donor T-cell immune responses can eradicate lymphomas after allogeneic hematopoietic stem cell transplantation (AHSCT), but can also damage healthy tissues resulting in harmful graft-versus-host disease (GVHD). Next-generation sequencing has recently identified many new genetic lesions in follicular lymphoma (FL). One such gene, tumor necrosis factor receptor superfamily 14 (TNFRSF14), abnormal in 40% of FL patients, encodes the herpes virus entry mediator (HVEM) which limits T-cell activation via ligation of the B- and T-lymphocyte attenuator. As lymphoma B cells can act as antigen-presenting cells, we hypothesized that TNFRSF14 aberrations that reduce HVEM expression could alter the capacity of FL B cells to stimulate allogeneic T-cell responses and impact the outcome of AHSCT. In an in vitro model of alloreactivity, human lymphoma B cells with TNFRSF14 aberrations had reduced HVEM expression and greater alloantigen-presenting capacity than wild-type lymphoma B cells. The increased immune-stimulatory capacity of lymphoma B cells with TNFRSF14 aberrations had clinical relevance, associating with higher incidence of acute GVHD in patients undergoing AHSCT. FL patients with TNFRSF14 aberrations may benefit from more aggressive immunosuppression to reduce harmful GVHD after transplantation. Importantly, this study is the first to demonstrate the impact of an acquired genetic lesion on the capacity of tumor cells to stimulate allogeneic T-cell immune responses which may have wider consequences for adoptive immunotherapy strategies. © 2016 by The American Society of Hematology.

  8. Manifestation of Non-Alcoholic Fatty Liver Disease/Non-Alcoholic Steatohepatitis in Different Dietary Mouse Models

    Directory of Open Access Journals (Sweden)

    Vera HI Fengler

    2016-05-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD and non-alcoholic steatohepatitis (NASH, which are usually associated with obesity and metabolic syndrome, are considerable health and economic issues due to the rapid increase of their prevalence in Western society. Histologically, the diseases are characterised by steatosis, hepatic inflammation, and if further progressed, fibrosis. Dietary-induced mouse models are widely used in investigations of the development and progression of NAFLD and NASH; these models attempt to mimic the histological and metabolic features of the human diseases. However, the majority of dietary mouse models fail to reflect the whole pathophysiological spectrum of NAFLD and NASH. Some models exhibit histological features similar to those seen in humans while lacking the metabolic context, while others resemble the metabolic conditions leading to NAFLD in humans but fail to mimic the whole histological spectrum, including progression from steatosis to liver fibrosis, and thus fail to mimic NASH. This review summarises the advantages and disadvantages of the different dietary-induced mouse models of NAFLD and NASH, with a focus on the genetic background of several commonly used wild-type mouse strains as well as gender and age, which influence the development and progression of these liver diseases.

  9. Mouse Model Resources for Vision Research

    Directory of Open Access Journals (Sweden)

    Jungyeon Won

    2011-01-01

    Full Text Available The need for mouse models, with their well-developed genetics and similarity to human physiology and anatomy, is clear and their central role in furthering our understanding of human disease is readily apparent in the literature. Mice carrying mutations that alter developmental pathways or cellular function provide model systems for analyzing defects in comparable human disorders and for testing therapeutic strategies. Mutant mice also provide reproducible, experimental systems for elucidating pathways of normal development and function. Two programs, the Eye Mutant Resource and the Translational Vision Research Models, focused on providing such models to the vision research community are described herein. Over 100 mutant lines from the Eye Mutant Resource and 60 mutant lines from the Translational Vision Research Models have been developed. The ocular diseases of the mutant lines include a wide range of phenotypes, including cataracts, retinal dysplasia and degeneration, and abnormal blood vessel formation. The mutations in disease genes have been mapped and in some cases identified by direct sequencing. Here, we report 3 novel alleles of Crxtvrm65, Rp1tvrm64, and Rpe65tvrm148 as successful examples of the TVRM program, that closely resemble previously reported knockout models.

  10. The Addition of the BTK Inhibitor Ibrutinib to Anti-CD19 Chimeric Antigen Receptor T Cells (CART19) Improves Responses against Mantle Cell Lymphoma.

    Science.gov (United States)

    Ruella, Marco; Kenderian, Saad S; Shestova, Olga; Fraietta, Joseph A; Qayyum, Sohail; Zhang, Qian; Maus, Marcela V; Liu, Xiaobin; Nunez-Cruz, Selene; Klichinsky, Michael; Kawalekar, Omkar U; Milone, Michael; Lacey, Simon F; Mato, Anthony; Schuster, Stephen J; Kalos, Michael; June, Carl H; Gill, Saar; Wasik, Mariusz A

    2016-06-01

    Responses to therapy with chimeric antigen receptor T cells recognizing CD19 (CART19, CTL019) may vary by histology. Mantle cell lymphoma (MCL) represents a B-cell malignancy that remains incurable despite novel therapies such as the BTK inhibitor ibrutinib, and where data from CTL019 therapy are scant. Using MCL as a model, we sought to build upon the outcomes from CTL019 and from ibrutinib therapy by combining these in a rational manner. MCL cell lines and primary MCL samples were combined with autologous or normal donor-derived anti-CD19 CAR T cells along with ibrutinib. The effect of the combination was studied in vitro and in mouse xenograft models. MCL cells strongly activated multiple CTL019 effector functions, and MCL killing by CTL019 was further enhanced in the presence of ibrutinib. In a xenograft MCL model, we showed superior disease control in the CTL019- as compared with ibrutinib-treated mice (median survival not reached vs. 95 days, P ibrutinib to CTL019 and showed that 80% to 100% of mice in the CTL019 + ibrutinib arm and 0% to 20% of mice in the CTL019 arm, respectively, remained in long-term remission (P ibrutinib represents a rational way to incorporate two of the most recent therapies in MCL. Our findings pave the way to a two-pronged therapeutic strategy in patients with MCL and other types of B-cell lymphoma. Clin Cancer Res; 22(11); 2684-96. ©2016 AACR. ©2016 American Association for Cancer Research.

  11. Lenalidomide and Combination Chemotherapy (DA-EPOCH-R) in Treating Patients With MYC-Associated B-Cell Lymphomas

    Science.gov (United States)

    2017-09-28

    Adult Grade III Lymphomatoid Granulomatosis; B-cell Chronic Lymphocytic Leukemia; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Progressive Hairy Cell Leukemia, Initial Treatment; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage 0 Chronic Lymphocytic Leukemia; Stage I Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Mixed Cell Lymphoma; Stage I Adult Diffuse Small Cleaved Cell Lymphoma; Stage I Adult Hodgkin Lymphoma; Stage I Adult Immunoblastic Large Cell Lymphoma; Stage I Chronic Lymphocytic Leukemia; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Grade 3 Follicular Lymphoma; Stage I Mantle Cell Lymphoma; Stage I Marginal Zone Lymphoma; Stage I Small Lymphocytic Lymphoma; Stage II Adult Hodgkin Lymphoma; Stage II Chronic Lymphocytic

  12. Primary Follicular Lymphoma of the Common Bile Duct Mimicking Cholangiocarcinoma

    Directory of Open Access Journals (Sweden)

    Khaled Youssef Elbanna

    2014-01-01

    Full Text Available Primary non-Hodgkin′s lymphoma of the common bile duct is extremely rare. We present a case with history of inflammatory bowel disease and clinical manifestations of obstructive jaundice. Abdominal magnetic resonance imaging with magnetic resonance cholangiopancreatography (MRCP was done and demonstrated tight stricture at the middle part of common bile duct, and radiological findings were supportive of extra-hepatic cholangiocarcinoma. Whipple′s procedure was performed and the case was histopathologically proven to be non-Hodgkin′s lymphoma of follicular subtype involving the common bile duct. Lymphoma of the hepatobiliary system is usually present as secondary manifestation of systemic malignant lymphoma. However, primary malignant lymphomas arising from the hepatobiliary tree are extremely rare. The radiological appearance of common bile duct lymphoma is very similar to cholangiocarcinoma, making preoperative diagnosis very difficult, as in our present case. We also compare the imaging findings of our case to those seen in reported cases of follicular lymphoma of the common bile duct.

  13. Gene Therapy in Treating Patients With Human Immunodeficiency Virus-Related Lymphoma Receiving Stem Cell Transplant

    Science.gov (United States)

    2018-01-02

    HIV Infection; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Plasmablastic Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Non-Hodgkin Lymphoma; Recurrent Burkitt Lymphoma; Recurrent Follicular Lymphoma; Stage III Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage IV Follicular Lymphoma; Stage IV Mantle Cell Lymphoma

  14. Ixazomib Citrate and Rituximab in Treating Patients With Indolent B-cell Non-Hodgkin Lymphoma

    Science.gov (United States)

    2018-02-05

    Chronic Lymphocytic Leukemia; Follicular Lymphoma; Lymphoplasmacytic Lymphoma; Mantle Cell Lymphoma; Marginal Zone Lymphoma; Recurrent Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Refractory Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Small Lymphocytic Lymphoma; Waldenstrom Macroglobulinemia

  15. Galantamine improves olfactory learning in the Ts65Dn mouse model of Down syndrome.

    Science.gov (United States)

    de Souza, Fabio M Simoes; Busquet, Nicolas; Blatner, Megan; Maclean, Kenneth N; Restrepo, Diego

    2011-01-01

    Down syndrome (DS) is the most common form of congenital intellectual disability. Although DS involves multiple disturbances in various tissues, there is little doubt that in terms of quality of life cognitive impairment is the most serious facet and there is no effective treatment for this aspect of the syndrome. The Ts65Dn mouse model of DS recapitulates multiple aspects of DS including cognitive impairment. Here the Ts65Dn mouse model of DS was evaluated in an associative learning paradigm based on olfactory cues. In contrast to disomic controls, trisomic mice exhibited significant deficits in olfactory learning. Treatment of trisomic mice with the acetylcholinesterase inhibitor galantamine resulted in a significant improvement in olfactory learning. Collectively, our study indicates that olfactory learning can be a sensitive tool for evaluating deficits in associative learning in mouse models of DS and that galantamine has therapeutic potential for improving cognitive abilities.

  16. The effect of age at exposure on the inactivating mechanisms and relative contributions of key tumor suppressor genes in radiation-induced mouse T-cell lymphomas

    Energy Technology Data Exchange (ETDEWEB)

    Sunaoshi, Masaaki [Radiobiology for Children' s Health Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Department of Biological Sciences, College of Science, Ibaraki University, Bunkyo 2-1-1, Mito, Ibaraki 310-8512 (Japan); Amasaki, Yoshiko; Hirano-Sakairi, Shinobu; Blyth, Benjamin J. [Radiobiology for Children' s Health Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Morioka, Takamitsu [Radiobiology for Children' s Health Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Radiation Effect Accumulation and Prevention Project, Fukushima Project Headquarters, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Kaminishi, Mutsumi [Radiobiology for Children' s Health Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Shang, Yi [Radiation Effect Accumulation and Prevention Project, Fukushima Project Headquarters, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Nishimura, Mayumi; Shimada, Yoshiya [Radiobiology for Children' s Health Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Radiation Effect Accumulation and Prevention Project, Fukushima Project Headquarters, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Tachibana, Akira [Department of Biological Sciences, College of Science, Ibaraki University, Bunkyo 2-1-1, Mito, Ibaraki 310-8512 (Japan); and others

    2015-09-15

    Highlights: • T-cell lymphoma incidence, latency and weight did not change with age at exposure. • Lymphomas had frequent loss of heterozygosity on chromosomes 4, 11 and 19. • These lesions targeted the Cdkn2a, Ikaros and Pten tumor suppressor genes. • Age at exposure may influence which tumor suppressor genes are lost in each tumor. • The mechanisms of tumor suppressor gene loss were different at each locus. - Abstract: Children are considered more sensitive to radiation-induced cancer than adults, yet any differences in genomic alterations associated with age-at-exposure and their underlying mechanisms remain unclear. We assessed genome-wide DNA copy number and mutation of key tumor suppressor genes in T-cell lymphomas arising after weekly irradiation of female B6C3F1 mice with 1.2 Gy X-rays for 4 consecutive weeks starting during infancy (1 week old), adolescence (4 weeks old) or as young adults (8 weeks old). Although T-cell lymphoma incidence was similar, loss of heterozygosity at Cdkn2a on chromosome 4 and at Ikaros on chromosome 11 was more frequent in the two older groups, while loss at the Pten locus on chromosome 19 was more frequent in the infant-irradiated group. Cdkn2a and Ikaros mutation/loss was a common feature of the young adult-irradiation group, with Ikaros frequently (50%) incurring multiple independent hits (including deletions and mutations) or suffering a single hit predicted to result in a dominant negative protein (such as those lacking exon 4, an isoform we have designated Ik12, which lacks two DNA binding zinc-finger domains). Conversely, Pten mutations were more frequent after early irradiation (60%) than after young adult-irradiation (30%). Homozygous Pten mutations occurred without DNA copy number change after irradiation starting in infancy, suggesting duplication of the mutated allele by chromosome mis-segregation or mitotic recombination. Our findings demonstrate that while deletions on chromosomes 4 and 11 affecting Cdkn2

  17. Differential Expression of Ccn4 and Other Genes Between Metastatic and Non-metastatic EL4 Mouse Lymphoma Cells

    OpenAIRE

    S. CHAHAL, MANPREET; TERESA KU, H.; ZHANG, ZHIHONG; M. LEGASPI, CHRISTIAN; LUO, ANGELA; M. HOPKINS, MANDI; E. MEIER, KATHRYN

    2016-01-01

    Background: Previous work characterized variants of the EL4 murine lymphoma cell line. Some are non-metastatic, and others metastatic, in syngenic mice. In addition, metastatic EL4 cells were stably transfected with phospholipase D2 (PLD2), which further enhanced metastasis. Materials and Methods: Microarray analyses of mRNA expression was performed for non-metastatic, metastatic, and PLD2-expressing metastatic EL4 cells. Results: Many differences were observed between non-metastatic and meta...

  18. Epstein-Barr virus-associated lymphomas.

    Science.gov (United States)

    Shannon-Lowe, Claire; Rickinson, Alan B; Bell, Andrew I

    2017-10-19

    Epstein-Barr virus (EBV), originally discovered through its association with Burkitt lymphoma, is now aetiologically linked to a remarkably wide range of lymphoproliferative lesions and malignant lymphomas of B-, T- and NK-cell origin. Some occur as rare accidents of virus persistence in the B lymphoid system, while others arise as a result of viral entry into unnatural target cells. The early finding that EBV is a potent B-cell growth transforming agent hinted at a simple oncogenic mechanism by which this virus could promote lymphomagenesis. In reality, the pathogenesis of EBV-associated lymphomas involves a complex interplay between different patterns of viral gene expression and cellular genetic changes. Here we review recent developments in our understanding of EBV-associated lymphomagenesis in both the immunocompetent and immunocompromised host.This article is part of the themed issue 'Human oncogenic viruses'. © 2017 The Authors.

  19. Fundus autofluorescence patterns in primary intraocular lymphoma.

    Science.gov (United States)

    Casady, Megan; Faia, Lisa; Nazemzadeh, Maryam; Nussenblatt, Robert; Chan, Chi-Chao; Sen, H Nida

    2014-02-01

    To evaluate fundus autofluorescence (FAF) patterns in patients with primary intraocular (vitreoretinal) lymphoma. Records of all patients with primary intraocular lymphoma who underwent FAF imaging at the National Eye Institute were reviewed. Fundus autofluorescence patterns were evaluated with respect to clinical disease status and the findings on fluorescein angiography and spectral-domain optical coherence tomography. There were 18 eyes (10 patients) with primary intraocular lymphoma that underwent FAF imaging. Abnormal autofluorescence in the form of granular hyperautofluorescence and hypoautofluorescence was seen in 11 eyes (61%), and blockage by mass lesion was seen in 2 eyes (11%). All eyes with granular pattern on FAF had active primary intraocular lymphoma at the time of imaging, but there were 5 eyes with unremarkable FAF, which were found to have active lymphoma. The most common pattern on fluorescein angiography was hypofluorescent round spots with a "leopard spot" appearance (43%). These hypofluorescent spots on fluorescein angiography correlated with hyperautofluorescent spots on FAF in 5 eyes (36%) (inversion of FAF). Nodular hyperreflective spots at the level of retinal pigment epithelium on optical coherence tomography were noted in 43% of eyes. The hyperautofluorescent spots on FAF correlated with nodular hyperreflective spots on optical coherence tomography in 6 eyes (43%). Granularity on FAF was associated with active lymphoma in majority of the cases. An inversion of FAF (hyperautofluorescent spots on FAF corresponding to hypofluorescent spots on fluorescein angiography) was observed in less than half of the eyes.

  20. Oral plasmablastic lymphoma as the first manifestation of AIDS*

    Science.gov (United States)

    do Vale, Daniela Assis; Rogado, Carolina Martelli; de Carvalho, Danielle Lima Corrêa; Trierveiler, Marilia; Ortega, Karem López

    2017-01-01

    Plasmablastic lymphoma is a non-Hodgkin lymphoma characterized by its plasmacytic differentiation and predilection for the oral cavity. It is among the lymphomas most commonly associated with AIDS. This report details a case of a HIV-positive patient with a 1-month history of an exophytic mass in the gingival area of the upper left quadrant. The diagnosis of plasmablastic lymphoma was made based on its histopathological and immunophenotypical features. She was treated with chemotherapy followed by autologous hematopoietic stem cell transplantation. Despite complete resolution of the lesion, the patient died of cardiorespiratory arrest. This case illustrates plasmablastic lymphoma as the first clinical manifestation of AIDS, highlighting the importance of differentiating between a potentially malignant lesion and other pathologic processes. PMID:29267464

  1. Combination of arsenic and interferon-α inhibits expression of KSHV latent transcripts and synergistically improves survival of mice with primary effusion lymphomas.

    Directory of Open Access Journals (Sweden)

    Hiba El Hajj

    Full Text Available BACKGROUND: Kaposi sarcoma-associated herpesvirus (KSHV is the etiologic agent of primary effusion lymphomas (PEL. PEL cell lines infected with KSHV, but negative for Epstein-Barr virus have a tumorigenic potential in non-obese diabetic/severe combined immunodeficient mice and result in efficient engraftment and formation of malignant ascites with notable abdominal distension, consistent with the clinical manifestations of PEL in humans. METHODOLOGY/PRINCIPAL FINDINGS: Using this preclinical mouse model, we demonstrate that the combination of arsenic trioxide and interferon-alpha (IFN inhibits proliferation, induces apoptosis and downregulates the latent viral transcripts LANA-1, v-FLIP and v-Cyc in PEL cells derived from malignant ascites. Furthermore, this combination decreases the peritoneal volume and synergistically increases survival of PEL mice. CONCLUSION/SIGNIFICANCE: These results provide a promising rationale for the therapeutic use of arsenic/IFN in PEL patients.

  2. [Gastric perforation by MALT lymphoma. Case report].

    Science.gov (United States)

    López-Zamudio, José; Ramírez-González, Luis Ricardo; Núñez-Márquez, Julia; Fuentes Orozco, Clotilde; González Ojeda, Alejandro; Leonher-Ruezga, Karla Lisseth

    2015-01-01

    Gastric non-Hodgkin lymphoma is a rare tumour that represents approximately 7% of all stomach cancers and 2% of all lymphomas. The most frequent location of gastric MALT (mucosa associated lymphoid tissue) lymphomas is in the antrum in 41% of the cases, and 33% can be multifocal. The risk of spontaneous perforation of a gastric MALT lymphoma is 4-10%. 24 year old male patient carrying the Human Immunodeficiency Virus, who began with signs and symptoms of acute abdomen and fever 72 hours before arriving in the emergency room. A computed tomography was performed that showed free fluid in the cavity, and gastric wall thickening. The patient underwent a laparotomy, finding absence of the anterior wall of the stomach, sealed with the left lobe of the liver, colon and omentum. Total gastrectomy, with oesophagosty and jejunostomy tube, was performed. Gastric perforation secondary to a MALT lymphoma is rare, with high mortality. There is limited information reported of this complication and should be highly suspected in order to provide appropriate treatment for a complication of this type. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

  3. Radiation therapy for primary orbital lymphoma

    International Nuclear Information System (INIS)

    Chao, Cliff K.S.; Lin Hsiusan; Rao Devineni, V.; Smith, Morton

    1995-01-01

    Purpose: The influence of tumor size, grade, thoroughness of staging workup, and radiation dose on disease control, radiation-related complications, and incidence of systemic progression of primary orbital lymphoma is analyzed. Methods and Materials: Twenty patients with Stage I primary orbital lymphoma were treated from August 1976 through August 1991 at Mallinckrodt Institute of Radiology. Staging workups included physical examination, chest x-ray, complete blood count (CBC), liver function test, and computerized tomography (CT) scan of the orbit, abdomen, and pelvis. Nineteen patients had bone marrow biopsy. The histological types based on the National Cancer Institute working formulation were 9 low-grade and 11 intermediate-grade, including five lymphocytic lymphomas of intermediate differentiation. The extension of disease and the volume of tumor were evaluated by CT scan of the orbit. The most commonly used radiation therapy technique was single anterior direct field with 4 MV or 6 MV photons. Lens was shielded or not treated in eight patients. Dose ranged from 20 to 43.2 Gy. Thirteen of 20 patients received 30 Gy. Minimum follow-up was 24 months (median, 4 years). Results: Local control was achieved in all 20 patients. One patient with lymphocytic lymphoma with intermediate differentiation developed disseminated disease. Actuarial disease-free survival (DFS) was 100% and 90% at 2 and 5 years, respectively. No retinopathy was observed. Cataracts were noted in seven patients at 1 to 10 years following irradiation (median, 2 years). Three patients developed lacrimal function disorder, however, no corneal ulceration occurred. Conclusions: Thirty Gy in 15 fractions appears to be a sufficient dose for local control with acceptable morbidity, especially for low-grade, as well as certain types of intermediate-grade lymphomas, such as diffuse small cleaved cell and lymphocytic lymphoma of intermediate differentiation. Systemic dissemination is minimal, provided local

  4. Radiation therapy for primary orbital lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Chao, Cliff K.S.; Hsiusan, Lin; Rao Devineni, V; Smith, Morton

    1995-02-15

    Purpose: The influence of tumor size, grade, thoroughness of staging workup, and radiation dose on disease control, radiation-related complications, and incidence of systemic progression of primary orbital lymphoma is analyzed. Methods and Materials: Twenty patients with Stage I primary orbital lymphoma were treated from August 1976 through August 1991 at Mallinckrodt Institute of Radiology. Staging workups included physical examination, chest x-ray, complete blood count (CBC), liver function test, and computerized tomography (CT) scan of the orbit, abdomen, and pelvis. Nineteen patients had bone marrow biopsy. The histological types based on the National Cancer Institute working formulation were 9 low-grade and 11 intermediate-grade, including five lymphocytic lymphomas of intermediate differentiation. The extension of disease and the volume of tumor were evaluated by CT scan of the orbit. The most commonly used radiation therapy technique was single anterior direct field with 4 MV or 6 MV photons. Lens was shielded or not treated in eight patients. Dose ranged from 20 to 43.2 Gy. Thirteen of 20 patients received 30 Gy. Minimum follow-up was 24 months (median, 4 years). Results: Local control was achieved in all 20 patients. One patient with lymphocytic lymphoma with intermediate differentiation developed disseminated disease. Actuarial disease-free survival (DFS) was 100% and 90% at 2 and 5 years, respectively. No retinopathy was observed. Cataracts were noted in seven patients at 1 to 10 years following irradiation (median, 2 years). Three patients developed lacrimal function disorder, however, no corneal ulceration occurred. Conclusions: Thirty Gy in 15 fractions appears to be a sufficient dose for local control with acceptable morbidity, especially for low-grade, as well as certain types of intermediate-grade lymphomas, such as diffuse small cleaved cell and lymphocytic lymphoma of intermediate differentiation. Systemic dissemination is minimal, provided local

  5. Systemic non-Hodgkin's lymphoma initially presenting as a bladder mass

    Directory of Open Access Journals (Sweden)

    Naveen Kumar Gupta

    2017-01-01

    Full Text Available Urinary bladder lymphomas are rare lesions which may be primary bladder lymphomas or part of systemic lymphoma with bladder involvement. We report a case of non-Hodgkin's lymphoma (NHL in a 73-year-old female who presented with bladder tumor which on evaluation revealed NHL with extensive systemic involvement. The management of such an advanced case is discussed here with literature review.

  6. A Mathematical Model of Skeletal Muscle Disease and Immune Response in the mdx Mouse

    Directory of Open Access Journals (Sweden)

    Abdul Salam Jarrah

    2014-01-01

    Full Text Available Duchenne muscular dystrophy (DMD is a genetic disease that results in the death of affected boys by early adulthood. The genetic defect responsible for DMD has been known for over 25 years, yet at present there is neither cure nor effective treatment for DMD. During early disease onset, the mdx mouse has been validated as an animal model for DMD and use of this model has led to valuable but incomplete insights into the disease process. For example, immune cells are thought to be responsible for a significant portion of muscle cell death in the mdx mouse; however, the role and time course of the immune response in the dystrophic process have not been well described. In this paper we constructed a simple mathematical model to investigate the role of the immune response in muscle degeneration and subsequent regeneration in the mdx mouse model of Duchenne muscular dystrophy. Our model suggests that the immune response contributes substantially to the muscle degeneration and regeneration processes. Furthermore, the analysis of the model predicts that the immune system response oscillates throughout the life of the mice, and the damaged fibers are never completely cleared.

  7. High-mobility group B1 (HMGB1) and receptor for advanced glycation end-products (RAGE) expression in canine lymphoma.

    Science.gov (United States)

    Sterenczak, Katharina A; Joetzke, Alexa E; Willenbrock, Saskia; Eberle, Nina; Lange, Sandra; Junghanss, Christian; Nolte, Ingo; Bullerdiek, Jörn; Simon, Daniela; Murua Escobar, Hugo

    2010-12-01

    Canine lymphoma is a commonly occurring, spontaneously developing neoplasia similar to human non-Hodgkin's lymphoma and, thus, is used as a valuable model for human malignancy. HMGB1 and RAGE are strongly associated with tumour progression and vascularisation. Consequently, deregulated RAGE and HMGB1 may play an important role in the mechanisms involved in lymphoma progression. Expression patterns of HMGB1 and RAGE were analysed in 22 canine lymphoma and three canine non-neoplastic control samples via real time PCR and canine beta-glucuronidase gene (GUSB) as endogenous control. HMGB1 was up-regulated in the neoplastic samples, while RAGE expression remained inconspicuous. This study demonstrated similar mechanisms in lymphoma progression in humans and dogs due to overexpression of HMGB1, which was described in human lymphomas. RAGE remained stable in terms of expression indicating that the extracellular HMGB1-induced effects are regulated by HMGB1 itself.

  8. Lymphoma of uterine cervix: magnetic resonance imaging findings

    Energy Technology Data Exchange (ETDEWEB)

    Kanaan, Daniel; Constantino, Carolina Pesce Lamas; Souza, Rodrigo Canellas de, E-mail: daniel.kanaan@hotmail.com [Department of Radiology, Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil); Parente, Daniella Braz [Instituto D' Or de Pesquisa e Ensino, Rio de Janeiro, RJ (Brazil)

    2012-05-15

    Lymphoma of the cervix is a rare disease. About 1.0% to 1.5% of extranodal lymphomas originates in the female genital tract. The clinical presentation of this condition is nonspecific and magnetic resonance imaging is important for diagnostic elucidation. The present report describes the case of a 80-year-old patient with lumbar pain, whose magnetic resonance imaging showed a large uterine mass. The final diagnosis was lymphoma. (author)

  9. An oncogenic axis of STAT-mediated BATF3 upregulation causing MYC activity in classical Hodgkin lymphoma and anaplastic large cell lymphoma.

    Science.gov (United States)

    Lollies, A; Hartmann, S; Schneider, M; Bracht, T; Weiß, A L; Arnolds, J; Klein-Hitpass, L; Sitek, B; Hansmann, M-L; Küppers, R; Weniger, M A

    2018-01-01

    Classical Hodgkin lymphoma (cHL) and anaplastic large cell lymphoma (ALCL) feature high expression of activator protein-1 (AP-1) transcription factors, which regulate various physiological processes but also promote lymphomagenesis. The AP-1 factor basic leucine zipper transcription factor, ATF-like 3 (BATF3), is highly transcribed in cHL and ALCL; however, its functional importance in lymphomagenesis is unknown. Here we show that proto-typical CD30 + lymphomas, namely cHL (21/30) and primary mediastinal B-cell lymphoma (8/9), but also CD30 + diffuse large B-cell lymphoma (15/20) frequently express BATF3 protein. Mass spectrometry and co-immunoprecipitation established interactions of BATF3 with JUN and JUNB in cHL and ALCL lines. BATF3 knockdown using short hairpin RNAs was toxic for cHL and ALCL lines, reducing their proliferation and survival. We identified MYC as a critical BATF3 target and confirmed binding of BATF3 to the MYC promoter. JAK/STAT signaling regulated BATF3 expression, as chemical JAK2 inhibition reduced and interleukin 13 stimulation induced BATF3 expression in cHL lines. Chromatin immunoprecipitation substantiated a direct regulation of BATF3 by STAT proteins in cHL and ALCL lines. In conclusion, we identified STAT-mediated BATF3 expression that is essential for lymphoma cell survival and promoted MYC activity in cHL and ALCL, hence we recognized a new oncogenic axis in these lymphomas.

  10. Effect of CPAP in a Mouse Model of Hyperoxic Neonatal Lung Injury

    Science.gov (United States)

    Reyburn, Brent; Fiore, Juliann M. Di; Raffay, Thomas; Martin, Richard J.; Y.S., Prakash; Jafri, Anjum; MacFarlane, Peter M.

    2015-01-01

    Background Continuous positive airway pressure [CPAP] and supplemental oxygen have become the mainstay of neonatal respiratory support in preterm infants. Although oxygen therapy is associated with respiratory morbidities including bronchopulmonary dysplasia [BPD], the long-term effects of CPAP on lung function are largely unknown. We used a hyperoxia-induced mouse model of BPD to explore the effects of daily CPAP during the first week of life on later respiratory system mechanics. Objective To test the hypothesis that daily CPAP in a newborn mouse model of BPD improves longer term respiratory mechanics. Methods Mouse pups from C57BL/6 pregnant dams were exposed to room air [RA] or hyperoxia [50% O2, 24hrs/day] for the first postnatal week with or without exposure to daily CPAP [6cmH2O, 3hrs/day]. Respiratory system resistance [Rrs] and compliance [Crs] were measured following a subsequent 2 week period of room RA recovery. Additional measurements included radial alveolar counts and macrophage counts. Results Mice exposed to hyperoxia had significantly elevated Rrs, decreased Crs, reduced alveolarization, and increased macrophage counts at three weeks compared to RA treated mice. Daily CPAP treatment significantly improved Rrs, Crs and alveolarization, and decreased lung macrophage infiltration in hyperoxia-exposed pups. Conclusions We have demonstrated that daily CPAP had a longer term benefit on baseline respiratory system mechanics in a neonatal mouse model of BPD. We speculate that this beneficial effect of CPAP was the consequence of a decrease in the inflammatory response and resultant alveolar injury associated with hyperoxic newborn lung injury. PMID:26394387

  11. Increasing incidence of ophthalmic lymphoma in Denmark from 1980 to 2005

    DEFF Research Database (Denmark)

    Sjö, Lene D; Ralfkiær, Elisabeth Methner; Prause, Jan U

    2008-01-01

    included. There was an equal distribution of males and females. The most frequent lymphoma subtype was extranodal marginal zone B-cell lymphoma (MALT [mucosa-associated lymphoid tissue] lymphoma, 55.5%) and most cases were located in the orbit (56.8%). High-grade lymphoma subtypes were found more...

  12. Breast lymphoma

    African Journals Online (AJOL)

    To fulfil the criteria for primary breast lymphoma, the following characteristics were reqUired: (I) technically adequate specimens; (iI) mammary tissue and lymphomatous infiltrate in close association; (iil) no evidence of concurrent widespread disease; and (iv) no previous. Haematology/Oncology Division, Department of ...

  13. Lessons learned using different mouse models during space radiation-induced lung tumorigenesis experiments

    Science.gov (United States)

    Wang, Jian; Zhang, Xiangming; Wang, Ping; Wang, Xiang; Farris, Alton B.; Wang, Ya

    2016-06-01

    Unlike terrestrial ionizing radiation, space radiation, especially galactic cosmic rays (GCR), contains high energy charged (HZE) particles with high linear energy transfer (LET). Due to a lack of epidemiologic data for high-LET radiation exposure, it is highly uncertain how high the carcinogenesis risk is for astronauts following exposure to space radiation during space missions. Therefore, using mouse models is necessary to evaluate the risk of space radiation-induced tumorigenesis; however, which mouse model is better for these studies remains uncertain. Since lung tumorigenesis is the leading cause of cancer death among both men and women, and low-LET radiation exposure increases human lung carcinogenesis, evaluating space radiation-induced lung tumorigenesis is critical to enable safe Mars missions. Here, by comparing lung tumorigenesis obtained from different mouse strains, as well as miR-21 in lung tissue/tumors and serum, we believe that wild type mice with a low spontaneous tumorigenesis background are ideal for evaluating the risk of space radiation-induced lung tumorigenesis, and circulating miR-21 from such mice model might be used as a biomarker for predicting the risk.

  14. Primary cutaneous anaplastic large-cell lymphoma.

    Science.gov (United States)

    Perry, Edward; Karajgikar, Jay; Tabbara, Imad A

    2013-10-01

    Since the recognition of the anaplastic large-cell lymphomas in the 1980s, much has been learned about the diagnosis, clinical presentation, and treatment of these malignant conditions. The systemic and primary cutaneous types of anaplastic large cell lymphomas have been differentiated on clinical and immunophenotypical findings, but further research is required to elucidate their exact etiologies and pathogeneses. Primary cutaneous anaplastic large-cell lymphoma has a 95% disease-specific 5-year survival, owing partly to the relatively benign course of the disease and partly to the variety of effective treatments that are available. As with many other oncological diseases, new drugs are continually being tested and developed, with immunotherapy and biological response modifiers showing promise.

  15. Characteristics of Hodgkin's lymphoma after infectious mononucleosis

    DEFF Research Database (Denmark)

    Hjalgrim, Henrik; Askling, Johan; Rostgaard, Klaus

    2003-01-01

    BACKGROUND: Infectious mononucleosis-related Epstein-Barr virus (EBV) infection has been associated with an increased risk of Hodgkin's lymphoma in young adults. Whether the association is causal remains unclear. METHODS: We compared the incidence rates of Hodgkin's lymphoma in two population...

  16. A Challenging Case of Primary Breast Hodgkin's Lymphoma.

    Science.gov (United States)

    Zarnescu, Narcis Octavian; Iliesiu, Andreea; Procop, Alexandru; Tampa, Mircea; Matei, Clara; Sajin, Maria; Costache, Mariana; Dumitru, Adrian; Lazaroiu, Anca Mihaela

    2015-03-01

    Primary breast lymphoma (PBL) is a rare entity accounting for less than 1% of all breast malignancies. Diagnostic criteria for primary Hodgkin's lymphoma of the breast are: the presence of sufficient tissue for diagnosis, close interaction between mammary tissue and lymphomatous infiltrate and no evidence or prior diagnosis of widespread lymphoma. Our case illustrates an unusual presentation of Hodgkin's lymphoma of the breast: clinically as inflammatory breast cancer and core biopsy as granulomatous mastitis, the final diagnosis requiring surgical biopsy. Current information regarding this entity is scant, mainly build upon its rarity. In this paper we assess the clinical presentation, the step-by-step diagnosis, the treatment and the importance of immunohistochemistry in this uncommon condition.

  17. Pediatric Burkitt lymphoma presenting as acute pancreatitis: MRI characteristics

    Energy Technology Data Exchange (ETDEWEB)

    Amodio, John; Brodsky, Jennie E. [SUNY Downstate Medical Center, Department of Radiology, Brooklyn, NY (United States)

    2010-05-15

    Acute pancreatitis is a rare initial presentation of non-Hodgkin lymphoma with few reported cases described in older adults and even fewer in children. MRI features of Burkitt lymphoma of the pancreas are sparse in the radiologic literature. We present a 6-year-old boy who presented with pancreatitis and obstructive jaundice, which was the result of Burkitt lymphoma of the pancreas. The imaging findings of pancreatic involvement of Burkitt lymphoma on MRI are discussed and the contributory role of the radiologist in guiding the appropriate clinical work-up of this disease is highlighted. (orig.)

  18. Can metabolic tumor parameters on primary staging 18F-FDG PET/CT aid in risk stratification of primary central nervous system lymphomas for patient management as a prognostic model?

    Science.gov (United States)

    Okuyucu, K; Alagoz, E; Ince, S; Ozaydin, S; Arslan, N

    Primary central nervous system (CNS) lymphoma is an aggressive and fatal extranodal non-Hodgkin lymphoma jailed in CNS at initial diagnosis. Its prognosis is poor and the disease has a fatal outcome when compared with systemic non-Hodgkin lymphoma. A few baseline risk stratification scoring systems have been suggested to estimate the prognosis mainly based on serum lactate dehydrogenase level,age, Karnofsky performance score, involvement of deep brain structures and cerebrospinal fluid protein concentration. 18 F-FDG PET/CT has a high prognostic value with respect to overall survival and disease-free survival in many cancers and lymphomas. We aimed to investigate metabolic tumor indexes on primary staging 18 F-FDG PET/CT as prognostic markers in primary CNS lymphoma. Fourteen patients with primary CNS diffuse large B-cell lymphoma (stage i) were enrolled in this retrospective cohort study. Primary staging 18 F-FDG PET/CT was performed and quantitative parameters like maximum standardized uptake value, average standardized uptake value, metabolic tumor volume and total lesion glycolysis (TLG) were calculated for all patients before the treatment. Cox regression models were performed to determine their relation with survival time. In the evaluation of all potential risk factors impacting recurrence/metastases (age, sex, serum lactate dehydrogenase, involvement of deep brain structures, maximum standardized uptake value, average standardized uptake value, metabolic tumor volume, and TLG) with univariate analysis, TLG remained statistically significant (P=.02). Metabolic tumor parameters are useful in prognosis estimation of primary CNS lymphomas, especially TLG, which is the most important one and may play a role in patient management. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

  19. Automatic Assessment of Craniofacial Growth in a Mouse Model of Crouzon Syndrome

    DEFF Research Database (Denmark)

    Thorup, Signe Strann; Larsen, Rasmus; Darvann, Tron Andre

    2009-01-01

    for each mouse-type; growth models were created using linear interpolation and visualized as 3D animations. Spatial regions of significantly different growth were identified using the local False Discovery Rate method, estimating the expected percentage of false predictions in a set of predictions. For all......-rigid volumetric image registration was applied to micro-CT scans of ten 4-week and twenty 6-week euthanized mice for growth modeling. Each age group consisted of 50% normal and 50% Crouzon mice. Four 3D mean shapes, one for each mouse-type and age group were created. Extracting a dense field of growth vectors...... a tool for spatially detailed automatic phenotyping. MAIN OBJECTIVES OF PRESENTATION: We will present a 3D growth model of normal and Crouzon mice, and differences will be statistically and visually compared....

  20. Molecular Alterations in a Mouse Cardiac Model of Friedreich Ataxia

    DEFF Research Database (Denmark)

    Anzovino, Amy; Chiang, Shannon; Brown, Bronwyn E

    2017-01-01

    mechanisms. Using a mouse conditional frataxin knockout (KO) model in the heart and skeletal muscle, we examined the Nrf2 pathway in these tissues. Frataxin KO results in fatal cardiomyopathy, whereas skeletal muscle was asymptomatic. In the KO heart, protein oxidation and a decreased glutathione...

  1. CT appearances of mucosa-associated lymphoid tissue (MALT) lymphoma

    International Nuclear Information System (INIS)

    Kessar, P.; Norton, A.; Rohatiner, A.Z.S.; Lister, T.A.; Reznek, R.H.

    1999-01-01

    Mucosa-associated lymphoid tissue (MALT) lymphoma is a low-grade lymphoma that differs from high-grade non-Hodgkin lymphoma both clinically and histologically. The CT appearances of MALT lymphoma are described. Of 40 patients referred with biopsy-proven MALT lymphoma, only seven had not had gastrectomy or chemotherapy prior to CT examination. The CT scans of these seven cases were analysed for the degree and extent of gastric wall thickening, enlargement of abdominal and extra-abdominal lymph nodes, and presence of extranodal disease. In all patients the stomach was distended with oral contrast medium and scans performed at narrow collimation, after intravenous administration of 20 mg hyoscine butylbromide. In six patients focal thickening of the gastric wall was 1 cm or less. One patient had thickening of over 4 cm. There was no enlargement of abdominal or extra-abdominal lymph nodes or extension to adjacent organs. Thus on CT, at presentation, MALT lymphoma results in minimal gastric wall thickening, unlike high-grade non-Hodgkin lymphoma, which typically causes bulky gastric disease, nodal enlargement and extension into adjacent organs. CT is therefore of limited value in monitoring response to treatment. With disease greater than minimal thickening, transformation to a higher grade should be considered. (orig.)

  2. Oroxin B selectively induces tumor-suppressive ER stress and concurrently inhibits tumor-adaptive ER stress in B-lymphoma cells for effective anti-lymphoma therapy

    International Nuclear Information System (INIS)

    Yang, Ping; Fu, Shilong; Cao, Zhifei; Liao, Huaidong; Huo, Zihe; Pan, Yanyan; Zhang, Gaochuan; Gao, Aidi; Zhou, Quansheng

    2015-01-01

    Cancer cells have both tumor-adaptive and -suppressive endoplasmic reticulum (ER) stress machineries that determine cell fate. In malignant tumors including lymphoma, constant activation of tumor-adaptive ER stress and concurrent reduction of tumor-suppressive ER stress favors cancer cell proliferation and tumor growth. Current ER stress-based anti-tumor drugs typically activate both tumor-adaptive and -suppressive ER stresses, resulting in low anti-cancer efficacy; hence, selective induction of tumor-suppressive ER stress and inhibition of tumor-adaptive ER stress are new strategies for novel anti-cancer drug discovery. Thus far, specific tumor-suppressive ER stress therapeutics have remained absent in clinical settings. In this study, we explored unique tumor-suppressive ER stress agents from the traditional Chinese medicinal herb Oroxylum indicum, and found that a small molecule oroxin B selectively induced tumor-suppressive ER stress in malignant lymphoma cells, but not in normal cells, effectively inhibited lymphoma growth in vivo, and significantly prolonged overall survival of lymphoma-xenografted mice without obvious toxicity. Mechanistic studies have revealed that the expression of key tumor-adaptive ER-stress gene GRP78 was notably suppressed by oroxin B via down-regulation of up-stream key signaling protein ATF6, while tumor-suppressive ER stress master gene DDIT3 was strikingly activated through activating the MKK3-p38 signaling pathway, correcting the imbalance between tumor-suppressive DDIT3 and tumor-adaptive GRP78 in lymphoma. Together, selective induction of unique tumor-suppressive ER stress and concurrent inhibition of tumor-adaptive ER stress in malignant lymphoma are new and feasible approaches for novel anti-lymphoma drug discovery and anti-lymphoma therapy. - Highlights: • Oroxin B selectively induces tumor-suppressive ER stress in B-lymphoma cells. • Oroxin B significantly prolonged overall survival of lymphoma-xenografted mice.

  3. Oroxin B selectively induces tumor-suppressive ER stress and concurrently inhibits tumor-adaptive ER stress in B-lymphoma cells for effective anti-lymphoma therapy

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Ping; Fu, Shilong; Cao, Zhifei; Liao, Huaidong; Huo, Zihe; Pan, Yanyan; Zhang, Gaochuan; Gao, Aidi; Zhou, Quansheng, E-mail: zhouqs@suda.edu.cn

    2015-10-15

    Cancer cells have both tumor-adaptive and -suppressive endoplasmic reticulum (ER) stress machineries that determine cell fate. In malignant tumors including lymphoma, constant activation of tumor-adaptive ER stress and concurrent reduction of tumor-suppressive ER stress favors cancer cell proliferation and tumor growth. Current ER stress-based anti-tumor drugs typically activate both tumor-adaptive and -suppressive ER stresses, resulting in low anti-cancer efficacy; hence, selective induction of tumor-suppressive ER stress and inhibition of tumor-adaptive ER stress are new strategies for novel anti-cancer drug discovery. Thus far, specific tumor-suppressive ER stress therapeutics have remained absent in clinical settings. In this study, we explored unique tumor-suppressive ER stress agents from the traditional Chinese medicinal herb Oroxylum indicum, and found that a small molecule oroxin B selectively induced tumor-suppressive ER stress in malignant lymphoma cells, but not in normal cells, effectively inhibited lymphoma growth in vivo, and significantly prolonged overall survival of lymphoma-xenografted mice without obvious toxicity. Mechanistic studies have revealed that the expression of key tumor-adaptive ER-stress gene GRP78 was notably suppressed by oroxin B via down-regulation of up-stream key signaling protein ATF6, while tumor-suppressive ER stress master gene DDIT3 was strikingly activated through activating the MKK3-p38 signaling pathway, correcting the imbalance between tumor-suppressive DDIT3 and tumor-adaptive GRP78 in lymphoma. Together, selective induction of unique tumor-suppressive ER stress and concurrent inhibition of tumor-adaptive ER stress in malignant lymphoma are new and feasible approaches for novel anti-lymphoma drug discovery and anti-lymphoma therapy. - Highlights: • Oroxin B selectively induces tumor-suppressive ER stress in B-lymphoma cells. • Oroxin B significantly prolonged overall survival of lymphoma-xenografted mice.

  4. Small cell lymphocytic variant of marginal zone lymphoma: A distinct form of marginal zone lymphoma derived from naïve B cells as a cutaneous counterpart to the naïve marginal zone lymphoma of splenic origin.

    Science.gov (United States)

    Magro, Cynthia M; Olson, Luke C

    2018-02-21

    Primary cutaneous marginal zone lymphoma most commonly represents an indolent form of cutaneous B cell lymphoma. However, epidermotropic marginal zone lymphoma, blastic marginal zone lymphoma and B cell dominant variants without isotype switching can be associated with extracutaneous dissemination. The presumptive cell of origin is a post germinal center B cell with plasmacytic features. In the extracutaneous setting, however, a naïve B cell origin has been proposed for a subset of marginal zone lymphomas, notably splenic marginal zone lymphoma. The author encountered 11 cases of atypical lymphocytic infiltration of the skin primarily occurring in older individuals with an upper arm and head and neck localization; there was a reproducible pattern of diffuse and nodular infiltration by small monomorphic-appearing B cells. Phenotypically, the infiltrate was one predominated by B cells exhibiting CD23 and IgD positivity without immunoreactivity for CD38 and there were either no plasma cells or only a few without light chain restriction. In cases presenting with a solitary lesion complete excision and/or radiation led to successful disease remission in all cases without recurrence or metastatic disease. Of three cases with multiple initial lesions, evidence of extracutaneous disease was seen in two cases and recurrence occurred in one case. No patients have died of lymphoma. Longer term follows up and additional cases are needed to determine if this subset of marginal zone lymphoma is associated with a worse prognosis. Copyright © 2018. Published by Elsevier Inc.

  5. Lymphoma diagnosis in histopathology using a multi-stage visual learning approach

    Science.gov (United States)

    Codella, Noel; Moradi, Mehdi; Matasar, Matt; Sveda-Mahmood, Tanveer; Smith, John R.

    2016-03-01

    This work evaluates the performance of a multi-stage image enhancement, segmentation, and classification approach for lymphoma recognition in hematoxylin and eosin (H and E) stained histopathology slides of excised human lymph node tissue. In the first stage, the original histology slide undergoes various image enhancement and segmentation operations, creating an additional 5 images for every slide. These new images emphasize unique aspects of the original slide, including dominant staining, staining segmentations, non-cellular groupings, and cellular groupings. For the resulting 6 total images, a collection of visual features are extracted from 3 different spatial configurations. Visual features include the first fully connected layer (4096 dimensions) of the Caffe convolutional neural network trained from ImageNet data. In total, over 200 resultant visual descriptors are extracted for each slide. Non-linear SVMs are trained over each of the over 200 descriptors, which are then input to a forward stepwise ensemble selection that optimizes a late fusion sum of logistically normalized model outputs using local hill climbing. The approach is evaluated on a public NIH dataset containing 374 images representing 3 lymphoma conditions: chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), and mantle cell lymphoma (MCL). Results demonstrate a 38.4% reduction in residual error over the current state-of-art on this dataset.

  6. PET imaging in pediatric Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    Hudson, M.M.; Krasin, M.J.; Kaste, S.C.

    2004-01-01

    Advances in diagnostic imaging technology, especially functional imaging modalities like positron emission tomography (PET), have significantly influenced the staging and treatment approaches used for pediatric Hodgkin's lymphoma. Today, the majority of children and adolescents diagnosed with Hodgkin's lymphoma will be cured following treatment with noncross-resistant combination chemotherapy alone or in combination with low-dose, involved-field radiation. This success produced a greater appreciation of long-term complications related to radiation, chemotherapy, and surgical staging that prompted significant changes in staging and treatment protocols for children and adolescents with Hodgkin's lymphoma. Contemporary treatment for pediatric Hodgkin's lymphoma uses a risk-adapted approach that reduces the number of combination chemotherapy cycles and radiation treatment fields and doses for patients with localized favorable disease presentation. Advances in diagnostic imaging technology have played a critical role in the development of these risk-adapted treatment regimens. The introduction of computed tomography (CT) provided an accurate and non-invasive modality to define nodal involvement below the diaphragm that motivated the change from surgical to clinical staging. The introduction of functional imaging modalities, like positron emission tomography (PET) scanning, provided the means to correlate tumor activity with anatomic features generated by CT and modify treatment based on tumor response. For centers with access to this modality, PET imaging plays an important role in staging, evaluating tumor response, planning radiation treatment fields, and monitoring after completion of therapy for pediatric Hodgkin's lymphoma. (orig.)

  7. Hypothalamic food intake regulation in a cancer-cachectic mouse model

    OpenAIRE

    Dwarkasing, Jvalini T.; van Dijk, Miriam; Dijk, Francina J.; Boekschoten, Mark V.; Faber, Joyce; Argilès, Josep M.; Laviano, Alessandro; Müller, Michael; Witkamp, Renger F.; van Norren, Klaske

    2013-01-01

    Background Appetite is frequently affected in cancer patients leading to anorexia and consequently insufficient food intake. In this study, we report on hypothalamic gene expression profile of a cancer-cachectic mouse model with increased food intake. In this model, mice bearing C26 tumour have an increased food intake subsequently to the loss of body weight. We hypothesise that in this model, appetite-regulating systems in the hypothalamus, which apparently fail in anorexia, are still able t...

  8. Recent technological advances in using mouse models to study ovarian cancer.

    Science.gov (United States)

    House, Carrie Danielle; Hernandez, Lidia; Annunziata, Christina Messineo

    2014-01-01

    Serous epithelial ovarian cancer (SEOC) is the most lethal gynecological cancer in the United States with disease recurrence being the major cause of morbidity and mortality. Despite recent advances in our understanding of the molecular mechanisms responsible for the development of SEOC, the survival rate for women with this disease has remained relatively unchanged in the last two decades. Preclinical mouse models of ovarian cancer, including xenograft, syngeneic, and genetically engineered mice, have been developed to provide a mechanism for studying the development and progression of SEOC. Such models strive to increase our understanding of the etiology and dissemination of ovarian cancer in order to overcome barriers to early detection and resistance to standard chemotherapy. Although there is not a single model that is most suitable for studying ovarian cancer, improvements have led to current models that more closely mimic human disease in their genotype and phenotype. Other advances in the field, such as live animal imaging techniques, allow effective monitoring of the microenvironment and therapeutic efficacy. New and improved preclinical mouse models, combined with technological advances to study such models, will undoubtedly render success of future human clinical trials for patients with SEOC.

  9. Bendamustine in the treatment of non-Hodgkin’s lymphomas

    Directory of Open Access Journals (Sweden)

    Fredrick Hagemeister

    2009-12-01

    Full Text Available Fredrick Hagemeister1, George Manoukian21Department of Lymphoma/Myeloma, The University of Texas M.D. Anderson Cancer Center Houston, TX, USA; 2Department of Internal Medicine, The University of Texas Health Science Center, Houston, TX, USAPurpose: To review available data using bendamustine alone and in combination with other chemotherapeutic agents in treatment of patients with non-Hodgkin’s lymphomas.Methods: Internet database searches and literature review.Results: Bendamustine was approved in March 2008 by the United States Food and Drug Administration for the treatment of patients with chronic lymphocytic leukemia. Many trials have been performed over the last decade using bendamustine not only as monotherapy, but also in combination with other agents including rituximab, vincristine, mitoxantrone, fludarabine, and other agents as therapy for patients with relapsed non-Hodgkin’s lymphomas, and recently was approved for use in therapy of patients with relapsed indolent lymphomas considered refractory to rituximab therapy. As monotherapy, bendamustine induces good responses with only minor side effects. In combination with other agents, efficacy improves, especially when given in combination with rituximab. The drug has also been studied in combination with rituximab as initial therapy for indolent lymphomas, and has excellent activity with less toxicity than R-CHOP (rituximab – cyclophosphamide, hydroxydaunorubicin [Adriamycin], Oncovin [vincristine], and prednisone/prednisolone.Conclusion: Overall, bendamustine has demonstrated promising results as therapy for non-Hodgkin’s lymphomas and should be included in the armamentarium of agents used to treat relapsed indolent non-Hodgkin’s lymphomas and may prove valuable as initial therapy for these diseases. Further studies are being conducted to demonstrate the efficacy of this drug in combination with other agents.Keywords: bendamustine, non-Hodgkin’s lymphomas, relapsed lymphoma

  10. Non-Hodgkin lymphoma in Romania: a single-centre experience.

    Science.gov (United States)

    Fetica, Bogdan; Achimas-Cadariu, Patriciu; Pop, Bogdan; Dima, Delia; Petrov, Ljubomir; Perry, Anamarija M; Nathwani, Bharat N; Müller-Hermelink, Hans K; Diebold, Jacques; MacLennan, Kenneth A; Fulop, Annamaria; Blaga, Mihaiela L; Coza, Daniela; Nicula, Florian Al; Irimie, Alexandru; Weisenburger, Dennis D

    2017-06-01

    Epidemiologic studies of non-Hodgkin lymphoma (NHL) in Eastern Europe are scarce in the literature. We report the experience of the "Ion Chiricuta" Institute of Oncology in Cluj-Napoca (IOCN), Romania, in the diagnosis and outcome of patients with NHL. We studied 184 consecutive NHL patients diagnosed in the Pathology Department of IOCN during the years 2004-2006. We also obtained epidemiological data from the Northwestern (NW) Cancer Registry. In the IOCN series, the most common lymphoma subtype was diffuse large B-cell lymphoma (43.5%), followed by the chronic lymphocytic leukaemia/small lymphocytic lymphoma (21.2%). T-cell lymphomas represented a small proportion (8.2%). The median age of the patients was 57 years, with a male-to-female ratio of 0.94. Patients with indolent B-cell lymphomas had the best overall survival, whereas those with mantle cell lymphoma had the worst survival. The NW Cancer Registry data showed that the occurrence of NHL in the NW region of Romania was higher in men [world age-standardized incidence rate/100 000 (ASR)-5.9; 95% CI 5.1-6.6] than in women (ASR-4.1; 95% CI 3.5-4.7) with age-standardized male-to-female ratio of 1.44 (p = 0.038). Chronic lymphocytic leukaemia/small lymphocytic lymphoma was the most common NHL in the NW region of Romania, accounting for 43% of all cases, followed by diffuse large B-cell lymphoma (36%). The 5-year, age-standardized cumulative relative survival for NHL in the County of Cluj in NW Romania, for the period of 2006-2010, was 51.4%, with 58.4% survival for men and 43.2% for women. Additional studies of NHL in Eastern Europe are needed. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  11. Adult T-cell leukemia/lymphoma treatment in Bahia, Brazil

    Directory of Open Access Journals (Sweden)

    Pedro Dantas Oliveira

    Full Text Available Abstract Background: Adult T-cell leukemia/lymphoma is a peripheral disease associated with human T-cell lymphotropic virus type 1. Treatment is carried out according to clinical type with watchful waiting being recommended for less aggressive types. Aggressive adult T-cell leukemia/lymphoma is generally treated with chemotherapy and/or antivirals. The objective of this study was to correlate the survival of patients diagnosed in Bahia, Brazil, with the therapeutic approaches employed and to evaluate what issues existed in their treatment processes. Methods: Eighty-three adult T-cell leukemia/lymphoma patients (26 smoldering, 23 chronic, 16 acute, 13 lymphoma and five primary cutaneous tumoral with available data were included in this study. Results: Complete response was achieved in seven smoldering patients with symptomatic treatment, in two with chronic disease using antivirals/chemotherapy, in one with acute disease using antivirals and in one lymphoma using the LSG15 regimen [vincristine, cyclophosphamide, doxorubicin, and prednisolone (VCAP; doxorubicin, ranimustine, and prednisolone (AMP; and vindesine, etoposide, carboplatin, and prednisolone (VECP]. Smoldering patients who received symptomatic treatment presented longer survival. Favorable chronic patients treated with antivirals presented longer survival compared to the unfavorable subtype. However, for the acute form, first-line chemotherapy was better, albeit without significance, than antivirals. Only one of the patients with lymphoma and primary cutaneous tumors responded. Conclusions: Watchful waiting associated with phototherapy represents the best option for smoldering adult T-cell leukemia/lymphoma with survival in Bahia being superior to that described in Japan. There was a trend of better results with zidovudine/interferon-alpha in favorable chronic disease. Excellent results were achieved in the lymphoma type treated with the LSG15 protocol. Patients are diagnosed late

  12. Testicular lymphoma

    DEFF Research Database (Denmark)

    Møller, Michael Boe; d'Amore, F; Christensen, Bjarne Egelund

    1994-01-01

    In a Danish population-based non-Hodgkin's lymphoma registry, 2687 newly diagnosed patients were registered from 1983 to 1992. 39 had testicular involvement (TL) (incidence 0.26/10(5)/year). Median age was 71 years. 24 cases had localised and 15 had disseminated disease. Histologically, all cases...

  13. MRI findings of pancreatic lymphoma and autoimmune pancreatitis: A comparative study

    Energy Technology Data Exchange (ETDEWEB)

    Ishigami, Kousei, E-mail: Ishigamikousei@aol.co [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582 (Japan); Tajima, Tsuyoshi; Nishie, Akihiro; Ushijima, Yasuhiro [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582 (Japan); Fujita, Nobuhiro [Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University (Japan); Asayama, Yoshiki; Kakihara, Daisuke; Irie, Hiroyuki [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582 (Japan); Ito, Tetsuhide; Igarashi, Hisato [Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University (Japan); Nakamura, Masafumi [Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University (Japan); Honda, Hiroshi [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582 (Japan)

    2010-06-15

    Purpose: To clarify whether there are differences in MRI findings between pancreatic lymphomas and autoimmune pancreatitis (AIP). Materials and methods: MRI of 8 patients with pancreatic lymphomas and 21 patients with AIP were retrospectively reviewed. For multifocal pancreatic lymphomas (n = 2) and AIP (n = 4), the largest 2 lesions were evaluated. Ten pancreatic lymphomas and 25 AIP were compared on three bases: the signal intensity on T2-weighted images, internal homogeneity, and presence or absence of capsule-like rim. In 8 lymphomas and 19 AIP, the enhancement pattern on dynamic MRI was compared, as well. Results: On T2-weighted images, pancreatic lymphomas comprised 5, 5 and 4 lesions with low (iso), slightly high, and moderately high intensity, respectively, while the numbers for AIP were 14, 10, and 1 (P < 0.01). Nine of 10 (90%) lymphomas appeared homogenous, and 11 of 25 (44%) AIP were homogenous (P < 0.05). A capsule-like rim was present in 9 of 25 (36%) AIP, but was not seen in lymphomas (P < 0.05). On dynamic MRI, 18 of 19 (94.7%) AIP showed persistent (n = 5) or delayed enhancement (n = 13), and 6 of 8 (75%) lymphomas showed low intensity without delayed enhancement (P < 0.001). Conclusion: MRI findings for pancreatic lymphomas and AIP were significantly different, which may be helpful for the differential diagnosis of these two diseases.

  14. Targeted immunotherapy in Hodgkin lymphoma

    DEFF Research Database (Denmark)

    Hutchings, Martin

    2015-01-01

    In this issue of Blood, Rothe et al introduce a new principle of targeted Hodgkin lymphoma (HL) immunotherapy in their report from a phase 1 study of the bispecific anti-CD30/CD16A antibody construct AFM13.......In this issue of Blood, Rothe et al introduce a new principle of targeted Hodgkin lymphoma (HL) immunotherapy in their report from a phase 1 study of the bispecific anti-CD30/CD16A antibody construct AFM13....

  15. Radioimmunotherapy of non-Hodgkin lymphoma

    International Nuclear Information System (INIS)

    Batista Cuellar, Juan F.

    2016-01-01

    Non-Hodgkin lymphoma have a worse prognosis compared with other varieties of lymphoma and conventional therapy has specific onco higher incidence of unsatisfactory answers becoming more frequent recurrences of the disease. Radioimmunotherapy has proven to be an effective adjuvant therapy often in cases where conventional therapy this not proving effective. In this paper an exhibition of the current international state of the therapeutic and experiences and possibilities that exist in our environment to develop their use is done. (author)

  16. Orbital and conunctival lymphoma treatment and prognosis

    International Nuclear Information System (INIS)

    Bessell, E.M.; Henk, J.M.; Whitelocke, R.A.F.; Wright, J.E.

    1988-01-01

    115 patients with lymphoid tumours presenting in the orbit were seen between 1970 and 1984. The histological types were high-grade malignant lymphoma - 18, low-grade malignant lymphoma - 43, and indeterminate lymphocytic lesions - 54. Eighteen patients were found to have disseminated lymphoma at presentation. The majority of the patients received radiotherapy to the orbit; local control was achieved in all cases and the ocular morbidity from radiotherapy was low with 11 patients developing lens opacities and 5 a dry eye. Survival of patients with stage I low-grade lymphoma adn indeterminate lymphocytic lesions was similar to that of a normal population of the same age distribution. The clinic features and dissemination pattern of the low-grade malignant lymphomata and the indeterminate lymphocytic lesions were identical, suggesting that most, if not all, lymphoid masses presenting in the orbit are neoplastic rather than reactive in nature. 28 refs.; 4 figs.; 5 tabs

  17. [Primary central nervous system lymphoma mimicking ventriculitis].

    Science.gov (United States)

    Yamamoto, Shiro; Nagano, Seiji; Shibata, Sumiya; Kunieda, Takeharu; Imai, Yukihiro; Kohara, Nobuo

    2013-01-01

    A 66-year-old man presented with deteriorated bradykinesia, gait disturbance, disorientation, and urinary incontinence for three weeks. Magnetic resonance imaging (MRI) showed dilatation of the ventricles. Cerebrospinal fluid (CSF) examination demonstrated lymphocytic pleocytosis, elevation of protein levels, and decreased of glucose levels. A gadolinium-enhanced MRI revealed lesions in the ventricular wall and choroid plexus, mimicking ventriculitis. No evidence of bacterial, fungal, mycobacterial, or viral infections were observed in the CSF. Flow cytometry of CSF showed predominance of CD20+, λ+ cells. PCR examination of CSF revealed positive IgH gene rearrangement, suggesting B cell lymphoma. Endoscopic brain biopsy showed diffuse large B cell lymphoma. As the patient had no evidence of lymphoma in the other organs, we made a diagnosed of primary central nervous system lymphoma (PCNSL). A limited intraventricular spread of PCNSL is rare but important as one of differential diagnosis of ventriculitis.

  18. Orbital and conunctival lymphoma treatment and prognosis

    Energy Technology Data Exchange (ETDEWEB)

    Bessell, E M; Henk, J M; Whitelocke, R A.F.; Wright, J E

    1988-12-01

    115 patients with lymphoid tumours presenting in the orbit were seen between 1970 and 1984. The histological types were high-grade malignant lymphoma - 18, low-grade malignant lymphoma - 43, and indeterminate lymphocytic lesions - 54. Eighteen patients were found to have disseminated lymphoma at presentation. The majority of the patients received radiotherapy to the orbit; local control was achieved in all cases and the ocular morbidity from radiotherapy was low with 11 patients developing lens opacities and 5 a dry eye. Survival of patients with stage I low-grade lymphoma adn indeterminate lymphocytic lesions was similar to that of a normal population of the same age distribution. The clinic features and dissemination pattern of the low-grade malignant lymphomata and the indeterminate lymphocytic lesions were identical, suggesting that most, if not all, lymphoid masses presenting in the orbit are neoplastic rather than reactive in nature. 28 refs.; 4 figs.; 5 tabs.

  19. Immuno- and chemotherapy in the treatment of non-Hodgkins lymphomas

    International Nuclear Information System (INIS)

    Dwilewicz-Trojaczek, J.; Charlinski, G.

    2009-01-01

    Non-Hodgkin's lymphomas is a heterogeneous group of neoplasms. The lymphomas have various origins: from B and T cells. REAL/WHO classification system of NHL subdivided these diseases into lymphoma from precursor and peripheral lymphocytes. Clinical course may be: very aggressive and aggressive (generally - curable disease); and indolent lymphoma (generally - curable disease). The treatment of each subtype NHL is different, correct diagnosis is critically important. In the treatment of aggressive NHL are used combined chemotherapy, the addition of monoclonal antibody has greatly increased its efficacy. There are several therapeutic strategies to treat indolent NHL. The treatment of asymptomatic indolent lymphoma offers no benefit, and these patients may be observed. Once symptomatic, front-line therapy consist of single agent or combination chemotherapy, often combined with monoclonal antibody. The monoclonal antibodies have revolutionized the treatment of NHL. Monoclonal antibody fixes the antigen on the membrane o f the lymphoma cells. Monoclonal antibodies there are unconjugated, used alone or combined with chemotherapy (immunochemotherapy) or combined with immunotoxins or radionuclides (radioimmunotherapy). This is the progress in the treatment of lymphoma. (authors)

  20. F.D.G.-PET scanning in managing patients with lymphoma

    International Nuclear Information System (INIS)

    Bodet-Milin, C.; Kraeber-Bodere, F.; Salaun, P.Y.; Crespin, C.; Vuillez, J.P.; Kraeber-Bodere, F.

    2009-01-01

    The place of positron emission tomography (PET) in the evaluation of diffuse at big cells B lymphomas and hodgkin lymphomas is validated. The clinical impact of the PET registered in end of therapy development is indisputable. recommendations must be followed for images interpretation. The PET is strongly recommended during the first evaluation of the disease because it is a reference examination that makes easy the interpretation at the end of the therapy and allows to evaluate the extension of the disease with a sensitivity and a specificity superior to the computerized tomography. the prognosis value of intermediate evaluations appears certain in the diffuse at big cells B lymphomas and the hodgkin lymphomas but the impact of an early therapy change induced by PET is still to determine. The criteria of interpretation of early evaluations are to standardize. for the other types of lymphomas, the PET can have an interest to confirm the the localized stages, especially for the follicular lymphomas and direct the biopsy for a patient ill of a low range lymphoma suspect of aggressive change. (N.C.)