Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0079731 (B-cell lymphoma)
 16,671 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A novel cell line, designated OHK, was established from ascites of a 59-year-old Japanese woman with diffuse large B-cell lymphoma showing a peculiar serosal tropism, as seen in primary effusion lymphomas (PEL). OHK exhibited a large pleomorphic morphology with irregular nuclei and distinct nucleoli, and included immunoblastic and Reed-Sternberg-like giant cells. On ultrastructural examination, rich intermediate filaments, and well-developed Golgi apparati and rough endoplasmic reticulum, were seen. Immunophenotypically, OHK lacked T and B cell-associated antigens, and had CD10, CD30, CD33 and CD138 antigens. Although OHK cells did not express immunoglobulin (Ig) protein, Southern blot analysis demonstrated clonal rearrangements of Ig heavy and light chain genes. These observations suggest that OHK cells are derived from preterminally differentiated B cells, and that they have features of PEL. Kaposi's sarcoma-associated herpesvirus and Epstein-Barr virus were not detected. OHK displayed hyperploid karyotypes with multiple structural abnormalities, and produced some cytokines such as macrophage-colony-stimulating factor (M-CSF), granulocyte-CSF, interleukin 6 and transforming growth factor beta 1. In particular, vascular endothelial growth factor (VEGF), whose stimulation of vascular permeability is thought to be critical to the pathogenesis of PEL, was also produced in large quantities. These results indicate that OHK may be a useful tool for the investigation of PEL.
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PMID:Establishment and characterization of a Kaposi's sarcoma-associated herpesvirus- and Epstein-Barr virus-negative malignant lymphoma cell line (OHK) with primary effusion lymphoma immunophenotype. 1184 5

Hypoxic preconditioning provides protection against ischemic brain lesions in animal models of cerebral ischemia-hypoxia. To analyze the underlying molecular mechanisms, we developed an in vitro model of hypoxic neuroprotection in cerebellar granule neurons (CGN) by reducing the oxygen tension to 1-5% for 1-24 hr. Exposure to 5% O2 for 9 hr resulted in reduction of cell death after potassium deprivation, treatment with 100 microm glutamate, or 500 microm 3-nitroproprioninc acid (3-NP) by 46, 22, and 55%, respectively. Shorter (1 or 3 hr) or longer (>12 hr) intervals or pretreatment with lower oxygen tension failed to rescue CGN from death. In contrast, toxicity of four different chemotherapeutic drugs [1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, cisplatine, topotecane, and vincristine] was unaffected by hypoxic preconditioning. The induction of protective effects was dependent on new protein synthesis. Protein levels of B-cell lymphoma protein-2 (BCL-2), BCL-x(L/S), heat shock protein 70/90, and BCL-2-associated death protein remained unaltered. CGN incubated at 5% O2 for 9 hr showed increased levels of the vascular endothelial growth factor (VEGF), the VEGF receptor-2 (VEGFR-2), phosphorylated Akt/protein kinase B (PKB), and extracellular signal-regulated kinase 1 (ERK1). Incubation with a neutralizing anti-VEGF antibody, a monoclonal antibody to VEGFR-2, wortmannin, or antisense-Akt/PKB, but not treatment with U0126, an ERK-inhibitor, reverted the resistance acquired by hypoxic preconditioning. Inhibition of VEGFR-2 blocked the activation of Akt/PKB. Finally, pretreatment with recombinant VEGF resulted in a hypoxia-resistant phenotype in the absence of hypoxic preconditioning. Our data are indicating a sequential requirement for VEGF/VEGFR-2 activation and Akt/PKB phosphorylation for neuronal survival mediated by hypoxic preconditioning and propose VEGF as a hypoxia-induced neurotrophic factor.
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PMID:Neuroprotection by hypoxic preconditioning requires sequential activation of vascular endothelial growth factor receptor and Akt. 1215 19

Hemorrhage at presentation in primary CNS lymphoma is exceedingly rare. We describe a patient with primary CNS lymphoma who presented with seizures and was found to have an intracerebral hemorrhage which prompted a cerebral angiogram. Ultimately pathologic evaluation of the lesion revealed a highly cellular B-cell lymphoma with marked hypervascularity and intense expression of vascular endothelial growth factor (VEGF). A review of four other recent cases of primary CNS lymphoma at our institution revealed less-intense VEGF immunoreactivity. This is the first report of VEGF expression in primary CNS lymphoma. The potential significance of VEGF expression with respect to the biology of this tumor is discussed.
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PMID:Hemorrhage and VEGF expression in a case of primary CNS lymphoma. 1216 Jan 41

Xenoengraftment of human cells in mice with severe combined immunodeficiency (SCID) has been used as a model system to study the mechanisms of B-cell lymphomagenesis. In the study reported here, we determined that SCID mice can also be used as a model to study angiogenesis in B-cell lymphomas. The C.B-17 scid/scid mice were xenotransplanted with Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCL), and we determined whether CD31, a marker found on endothelial cells, was detected in the human B-cell lymphomas that developed in these mice. Microvessel formation was identified by use of immunohistochemical staining for CD31. To assess possible mechanisms of angiogenic stimulus, we analyzed the expression of interleukin 8 (IL-8), a chemokine documented to promote angiogenesis, in non-small-cell lung cancer and bronchogenic carcinomas. We observed that a panel of LCL and LCL-lymphomas expressed IL-8 mRNA and protein. Neutralization of IL-8, however, did not inhibit lymphomagenesis, suggesting that IL-8 is not essential for angiogenesis in this model. To examine other parameters of angiogenesis, we identified expression of vascular endothelial growth factor in the lymphomas. These data suggest that angiogenesis accompanies EBV-associated B-cell lymphoma development, but IL-8 is not essential for this process. Thus, the SCID mouse model is amenable to testing of anti-angiogenic factors.
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PMID:Model of angiogenesis in mice with severe combined immunodeficiency (SCID) and xenoengrafted with Epstein-Barr virus-transformed B cells. 1513 68

The role of angiogenesis in lymphoproliferative diseases is not well established. We demonstrate here that human lymphoma cells secrete vascular endothelial growth factor (VEGF) and express VEGF receptor 1 (VEGFR-1) and VEGFR-2. Proliferation of non-Hodgkin lymphoma (NHL) cells under serum-free conditions was enhanced by the addition of VEGF and was blocked by VEGFR-1- and VEGFR-2-specific antibodies. To differentiate between VEGF-mediated autocrine and paracrine effects on lymphoma growth, NOD/SCID mice engrafted with human diffuse large B-cell lymphoma (DLBCL) were treated with species-specific antibodies against human VEGFR-1 (6.12), human VEGFR-2 (IMC-1C11), murine VEGFR-1 (MF-1), or murine VEGFR-2 (DC101). Treatment with 6.12 or DC101 (targeting tumor VEGFR-1 and host VEGFR-2) reduced established DLBCL xenograft growth, whereas treatment with IMC-1C11 or MF-1 (targeting tumor VEGFR-1 and host VEGFR-1) had no effect. Decreased tumor volumes after 6.12 and DC101 treatment correlated with increased tumor apoptosis and reduced vascularization, respectively, supporting the presence of autocrine VEGFR-1- and paracrine VEGFR-2-mediated pathways in lymphomagenesis. Inhibition of paracrine VEGF interactions (DC101) in these models was equivalent to their inhibition with rituximab. Combining DC101 with therapeutic agents (rituximab, 6.12, methotrexate) consistently improved tumor responses over those of single-agent therapy. These data support the further clinical development of VEGFR-targeted approaches for the therapy of aggressive DLBCL.
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PMID:Targeting autocrine and paracrine VEGF receptor pathways inhibits human lymphoma xenografts in vivo. 1523 24

The K1 gene of Kaposi sarcoma-associated herpesvirus (KSHV) encodes a transmembrane glycoprotein bearing a functional immunoreceptor tyrosine-based activation motif (ITAM). Previously, we reported that the K1 protein induced plasmablastic lymphomas in K1 transgenic mice, and that these lymphomas showed enhanced Lyn kinase activity. Here, we report that systemic administration of the nuclear factor kappa B (NF-kappaB) inhibitor Bay 11-7085 or an anti-vascular endothelial growth factor (VEGF) antibody significantly reduced K1 lymphoma growth in nude mice. Furthermore, in KVL-1 cells, a cell line derived from a K1 lymphoma, inhibition of Lyn kinase activity by the Src kinase inhibitor PP2 decreased VEGF induction, NF-kappaB activity, and the cell proliferation index by 50% to 75%. In contrast, human B-cell lymphoma BJAB cells expressing K1, but not the ITAM sequence-deleted mutant K1, showed a marked increase in Lyn kinase activity with concomitant VEGF induction and NF-kappaB activation, indicating that ITAM sequences were required for the Lyn kinase-mediated activation of these factors. Our results suggested that K1-mediated constitutive Lyn kinase activation in K1 lymphoma cells is crucial for the production of VEGF and NF-kappaB activation, both strongly implicated in the development of KSHV-induced lymphoproliferative disorders.
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PMID:Activation of Src kinase Lyn by the Kaposi sarcoma-associated herpesvirus K1 protein: implications for lymphomagenesis. 1566 17

Circulating inflammatory cytokines have a prognostic impact independent of the information provided by the International Prognostic Index (IPI) in diffuse large B-cell lymphoma (DLBCL). The present study characterized prognostic cytokines in relation to stage-specific B-cell differentiation antigens and bcl-2 protein expression, assessed by immunohistochemistry in de novo DLBCL. Serum levels of interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-alpha) were found to be significantly lower in patients with a germinal centre (GC) phenotype (co-expression of bcl-6 and CD10) compared with the non-GC phenotype. IL-6 and TNF-alpha levels were significantly elevated in patients expressing bcl-2 protein. Serum levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were not associated with the GC phenotype. On the contrary, both VEGF and bFGF were strongly correlated to bcl-2 expression. In survival analysis, IPI score remained the most important independent prognostic factor. However, IL-6 and VEGF, combined with non-GC phenotype and bcl-2 positivity, respectively, had a similar independent prognostic power as the IPI. In conclusion, our data suggest that inflammatory cytokines are differently distributed in the GC and non-GC phenotypes and correlate to bcl-2 expression. Combining these biomarkers may add to the prognostic information given by clinical variables in the IPI alone.
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PMID:Serum levels of inflammatory cytokines at diagnosis correlate to the bcl-6 and CD10 defined germinal centre (GC) phenotype and bcl-2 expression in patients with diffuse large B-cell lymphoma. 1575 85

Serous effusions are a common complication of lymphomas. Although the frequency of pleural effusion is 20-30% in non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD), the involvement of peritoneal and pericardial cavities is uncommon. Among lymphoma subtypes, T-cell neoplasms, especially the lymphoblastic lymphomas, more frequently involve the serous fluids. The thoracic duct obstruction and impaired lymphatic drainage appear to be the primary mechanism for pathogenesis of pleural effusion in HD and direct pleural infiltration is the predominant cause in NHL. There is wide variation in rate of positive cytologic findings of NHL in pleural effusion (22.2-94.1%). Cytologic features of specific lymphoma subtypes such as lymphoblastic lymphoma, follicular center cell lymphoma, including Burkitt-type lymphoma, marginal zone lymphoma, MALT lymphoma, and anaplastic large-cell lymphoma, etc., have been described in the literature. The differential diagnostic problems of lymphomas in serous effusions include reactive lymphocytoses, early involvement by lymphomatous process, small round-cell tumors (SRCT), and presence of look-alike of Reed-Sternberg cells. To overcome these difficulties, various ancillary studies, including immunocytochemistry (ICC), morphometry, flow cytometry (FCM), and cytogenetics/molecular genetics (PCR, in-situ hybridization, and Southern blotting), have been performed on effusion specimens. ICC not only distinguishes lymphomas from reactive lymphocytoses and SRCTs, it significantly modifies the morphologic diagnosis to achieve a better classification of lymphomas. Combined morphology and immunophenotyping by FCM, has a sensitivity as well as specificity of 100%. Morphometry also distinguishes reactive lymphocytoses from malignant lymphoma with a high degree of sensitivity (>85%) and specificity (>95%). Limitations of individual ancillary techniques can be overcome by using multiple parameters. Although lymphomas rarely present as serous effusions without the involvement of other thoracic and extrathoracic sites, a small group of lymphomas called primary effusion lymphomas (PEL) exhibit exclusive or dominant involvement of serous cavities, without a detectable solid tumor mass. This body cavity based lymphoma (BCBL) is a distinct clinicopathologic entity and is found predominantly in AIDS patients with preexisting Kaposi sarcoma. In the absence of obstructive or infiltrative tumor mass, its pathogenesis has been attributed to stimulation by vascular endothelial growth factor (VEGF)/vascular permeability factor (VPF), leading to vascular leakage. Cytomorphologically, PEL is usually a large-cell lymphoma, which appears to bridge features of large-cell immunoblastic and anaplastic large-cell lymphoma (ALCL). Most of these cases comprise a unique subgroup of B-cell lymphoma, with features of both high-grade anaplastic and B-immunoblastic lymphoma, but T-cell and/or natural killer cell immunophenotypes are described. Its association with various viral DNAs has been studied in detail by molecular techniques. Pleural effusion due to lymphomas, either primary or otherwise, is considered as one of the factors adversely influencing overall survival. The presence of pleural effusion at the time of presentation is not only associated with extremely poor outcome of lymphomas, it is also a predictor of disease relapse after chemotherapy and decreased survival. When the patients of lymphomatous pleural effusions with and without mediastinal mass present in respiratory distress, thoracocentesis is the initial diagnostic and therapeutic choice in these patients. In such situations, cytology along with ancillary studies not only gives a quick diagnosis of lymphoma, but also offers prognostically significant information such as classification of lymphomas, its grade and immunophenotype, and presence/absence of viral DNAs and tumor lysis syndrome.
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PMID:Serous effusions in malignant lymphomas: a review. 1660 59

Angiogenesis is known to play a major role in neoplasia, including hematolymphoid neoplasia. We assessed the relationships among angiogenesis and expression of vascular endothelial growth factor and its receptors in the context of clinically and biologically relevant subtypes of diffuse large B-cell lymphoma using immunohistochemical evaluation of tissue microarrays. We found that diffuse large B-cell lymphoma specimens showing higher local vascular endothelial growth factor expression showed correspondingly higher microvessel density, implying that lymphoma cells induce local tumor angiogenesis. In addition, local vascular endothelial growth factor expression was higher in those specimens showing higher expression of the receptors of the growth factor, suggesting an autocrine growth-promoting feedback loop. The germinal center-like and nongerminal center-like subtypes of diffuse large B-cell lymphoma were biologically and prognostically distinct. Interestingly, only in the more clinically aggressive nongerminal center-like subtype were microvessel densities significantly higher in specimens showing higher vascular endothelial growth factor expression; the same was true for the finding of higher vascular endothelial growth factor receptor-1 expression in conjunction with higher vascular endothelial growth factor expression. These differences may have important implications for the responsiveness of the two diffuse large B-cell lymphoma subtypes to anti-vascular endothelial growth factor and anti-angiogenic therapies.
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PMID:Microvessel density and expression of vascular endothelial growth factor and its receptors in diffuse large B-cell lymphoma subtypes. 1739 74

Probiotics are widely used as functional foods which have been advocated for the maintenance of gastrointestinal microflora equilibrium and treatment of gastrointestinal disorders. However, studying the role of probiotics in peptic ulcer disease is limited. The aim of the present study is to investigate the effect of a probiotic strain Lactobacillus rhamnosus GG on gastric ulcer and to elucidate the mechanisms involved. Gastric kissing ulcers were induced in rats by acetic acid (60% v/v). L. rhamnosus GG was given intragastrically at 10(8) cfu/day or 10(9) cfu/day for three consecutive days after ulcer induction. L. rhamnosus GG successfully colonized in the gastric mucosa especially at the ulcer margin. It also significantly and dose-dependently reduced gastric ulcer area. Cell apoptosis to cell proliferation ratio was strongly decreased and accompanied by significant up-regulation of ornithine decarboxylase (ODC) and B-cell lymphoma 2 (Bcl-2) protein expression at the ulcer margin. Angiogenesis was also significantly stimulated together with the induction of vascular endothelial growth factor (VEGF) expression. Furthermore, L. rhamnosus GG up-regulated the phosphorylation level of epidermal growth factor receptor (EGF receptor) without altering the total EGF receptor expression. These findings suggested that L. rhamnosus GG enhanced gastric ulcer healing via the attenuation of cell apoptosis to cell proliferation ratio and increase in angiogenesis. Regulators of these processes such as ODC, Bcl-2, VEGF and EGF receptor are likely to be involved in the healing action of L. rhamnosus GG for gastric ulcer.
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PMID:Probiotic Lactobacillus rhamnosus GG enhances gastric ulcer healing in rats. 1739 75


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