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)

In the present article we show that supernatants derived from lipopolysaccharide (LPS) or phorbol 12-myristate 13-acetate (PMA)-stimulated A-20 B cell lymphoma are able to induce polyclonal immunoglobulin (Ig) secretion by normal B cells in a T-cell-dependent manner. This activity could be blocked by neutralizing monoclonal antibodies against interferon-gamma, but not by monoclonal antibodies against interleukin (IL)-2, IL-4, IL-5, IL-6, IL-10 and granulocyte macrophage colony-stimulating factor (GM-CSF) or even a polyclonal antibody against tumor necrosis factor (TNF)-alpha. Furthermore, A-20 supernatants induced the production of measurable amounts of interferon-gamma by normal murine spleen cells and activates natural killer (NK) cells. Fractionation of factor-rich supernatants on a Sephacryl S-200 column revealed that the factor activity is located in the fractions corresponding to a molecular mass of 160-150 kDa and 80-70 kDa. The biological activities found in the A-20 supernatant are very similar to the ones described for the recently cloned human IL-12/NK cell stimulatory factor. These results suggest the existence of a murine analogous factor for the human IL-12 produced by A-20 B cell lymphoma.
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PMID:An activated murine B cell lymphoma line (A-20) produces a factor-like activity which is functionally related to human natural killer cell stimulatory factor. 135 72

Human immunodeficiency virus (HIV)-1 infection is associated with increased frequency of Kaposi's sarcoma and high-grade B-cell lymphoma. Several other cancers in HIV-1-infected individuals have been reported, although without statistically significant increase in their respective occurrences. Although HIV-1 does not infect either Kaposi's sarcoma-derived spindle cells or B lymphocytes in vivo, viral proteins in vitro have been shown to be mitogenic to both Kaposi's sarcoma-derived spindle cells and B lymphocytes. Furthermore, several cytokines influence directly and indirectly the proliferative differentiation capacity of these cells. These cytokines include interleukin-1, interleukin-4, interleukin-6, and tumor necrosis factor. Many of these cytokines also are regulated by HIV-1 infection of T lymphocytes and monocyte/macrophage. Furthermore, elevated levels of interleukin-1, interleukin-6 and tumor necrosis factor have been observed in patients with HIV-1 infection, particularly in advanced stages, when these tumors often manifest. Thus, it appears that although HIV-1 does not directly transform cells permissive to its infection, viral proteins directly and through regulation of cellular genes exert activities that may lead to the development of Kaposi's sarcoma and B-cell lymphoma.
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PMID:Pathogenesis of HIV-related malignancies. 175 80

Different immunotherapy regimens using s.c. recombinant interleukin-2 (rIL-2) were studied in 76 patients with progressive metastatic renal carcinoma, malignant melanoma, colorectal cancer, B-cell lymphoma, or Hodgkin's disease. To assess the immunomodulatory capacity of rIL-2, we measured serum levels of soluble interleukin-2 (sIL-2) receptors, gamma-interferon, tumor necrosis factor-alpha, and various lymphocyte subsets expressing the CD25 Tac IL-2 receptor and the CD56 natural killer (NK) associated antigen. Additionally, we measured serum antibodies specific to rIL-2 in order to evaluate immunogenicity of rIL-2. In all patients, a significant increase in sIL-2 receptor levels could be observed when comparing values on day 0 and after one treatment course. Patients developing a neutralizing anti-rIL-2 antibody exhibited significantly lower serum sIL-2 receptor levels than patients without antibody. Soluble IL-2 receptors correlated with the percentage of CD25 IL-2 receptor-positive peripheral blood lymphocytes. Both soluble and cell surface IL-2 receptors exhibited a significant increase during rIL-2 therapy but did not correlate with the percentage of CD56-positive peripheral blood lymphocytes. Measurement of treatment-induced secondary cytokines showed significant increases in gamma-interferon serum levels in a proportion of patients tested, although with considerable interindividual variability. No significant increase in mean tumor necrosis factor-alpha levels was observed during rIL-2 treatment in vivo. The percentage of CD56-positive NK cells correlated with the clinical outcome of rIL-2 therapy. Thus, partial or complete responders had an increase from a mean of 20% NK cells prior to therapy up to a mean of 40% after the first treatment course. In contrast, patients with progressive disease had a mean of 22 and 24% NK cells before and after treatment, respectively.
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PMID:Biological monitoring of low-dose interleukin 2 in humans: soluble interleukin 2 receptors, cytokines, and cell surface phenotypes. 193 92

By in vitro transformation with Epstein-Barr virus (EBV), we have previously established EBV+ lymphoblastoid cell lines (LCL) from a patient with leukemic centrocytic B cell lymphoma. EBV-transformed LCL and EBV genome-negative leukemic B cells showed identical chromosome aberrations and IgH gene rearrangements. In the present study we have analyzed the effect of exogenous cytokines [interleukin (IL) 1, 2, 3, 4, 6, tumor necrosis factor, lymphotoxin, transforming growth factor beta, (TGF-beta)] and anti-IgM antibodies on the in vitro proliferation of EBV- leukemic B cells and EBV-converted LCL. In contrast to conventional chronic lymphocytic leukemia, B cells of the patient DUL spontaneously proliferated for up to two weeks in the absence of exogenous lymphokines. The spontaneous proliferative capacity of clonal DUL B cells was not modulated by IL 1, IL 3, IL 6, TNF or LT. In vitro growth of DUL B cells was increased, however, by exogenous recombinant (r)IL 2, and was abrogated by TGF-beta, rIL 4 and anti-IgM. rIL 4 not only inhibited spontaneous B cell proliferation but also neutralized the enhancing effect of rIL 2. In contrast, growth of the EBV-transformed DUL LCL was not affected by any of these factors. These data demonstrate that in vitro infection and transformation of a clonal B cell population by EBV induces a switch in responsiveness to rIL 4, TGF-beta and anti-IgM. In addition, this report is the first to demonstrate an inhibitory effect of rIL 4 on a spontaneously proliferating human leukemic B cell clone.
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PMID:In vitro transformation by Epstein-Barr virus induces a switch in growth factor and anti-IgM responsiveness in a human leukemic B cell clone. 215 17

Twenty-six patients with advanced cancer refractory to standard therapy were treated with recombinant human tumor necrosis factor (rTNF) in a study aimed at determining the toxicity and tolerance of rTNF and at seeking evidence of antitumor activity. The study design involved two treatments per week for 4 weeks with alternating subcutaneous and intravenous (IV) administration, and weekly dose escalation through four levels in each patient. The dose range was 1 to 200 micrograms/m2 for IV bolus injection, and 5 to 250 micrograms/m2 for subcutaneous injection. Thirteen patients completed the full course. Early discontinuation of treatment was related to rTNF toxicity in seven cases. The major side effects were rigors, fever, headache, fatigue, and hypotension. Acute changes in granulocyte, lymphocyte, and monocyte counts, changes in serum zinc levels and plasma cortisol levels consistent with an acute phase response, and inflammation at the site of subcutaneous injection were also seen. At doses of 125 to 250 micrograms/m2, inflammation at the subcutaneous injection site was unacceptably severe. Minor changes were seen in hemostatic parameters. Hypotension was corrected by fluid administration and did not require treatment with vasopressors. Initial serum concentrations of rTNF were measured at five minutes after IV administration and were found to range from 2.5 ng/mL after a dose of 35 micrograms/m2 to 80 ng/mL after a dose of 200 micrograms/m2. The half-life of rTNF in the blood was 20 minutes. A decrease in lymph node size was observed in a patient with B cell lymphoma.
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PMID:Clinical pharmacology of recombinant human tumor necrosis factor in patients with advanced cancer. 368 77

Tumor infiltrating lymphocytes (TIL) were cultured from 17 B-cell lymphoma specimens derived from patients with predominantly low-grade malignancies. Specimens included 15 lymph-node biopsies, 1 malignant pleural effusion, and PBL from 1 patient with circulating lymphoma cells. The phenotypic and proliferative characteristics of TIL cultured in interleukin-2 (IL-2) were studied, as well as cytolysis and cytokine secretion in response to autologous tumor. Flow cytometry of fresh tumor suspensions showed that 50% of cells (median) were malignant B cells and 36% were infiltrating T lymphocytes. After culture for approximately 1 month, TIL were 75% +/- 8% CD3+ (mean +/- SEM), 47% +/- 8% CD4+ and 35% +/- 7% CD8+. TIL proliferation was modest in most cases: the median maximum expansion was 32-fold in 25 days. Lysis of autologous tumor in 4-hour 51Cr release assays was mediated by 2 of 12 TIL studied, but was nonspecific. However, these same two TIL, when cocultured with various tumor stimulators, preferentially secreted tumor necrosis factor-alpha and granulocyte-macrophage colony-stimulating factor after autologous tumor stimulation; unstimulated TIL secreted undetectable or barely detectable levels of these cytokines. In one TIL culture, cytokines were secreted by purified CD4+ TIL but not by CD8+ cells, and secretion was completely abrogated by the anti-major histocompatibility complex (MHC) class II antibody IVA12. Thus, although specific cytokine secretion by lymphoma TIL in response to autologous tumor was observed, it occurred in fewer than 20% of patients studied.
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PMID:Tumor-infiltrating lymphocytes derived from select B-cell lymphomas secrete granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-alpha in response to autologous tumor stimulation. 835 84

Cytokines play important roles in the pathogenesis of lymphomas. Cytokines either can be produced or exert effects on neoplastic or reactive cells. The secretion of cytokines can provide growth advantages for tumor cells in either an autocrine or a paracrine fashion. An elevated serum or tissue level of cytokines can contribute to the clinical and histopathologic alterations associated with malignant lymphomas. The effects of cytokines on the histopathologic changes are most noticeable in Hodgkin's disease (HD). The malignant (Hodgkin's-Reed-Sternberg) cells in HD have been shown to secrete interleukin-1 (IL-1), IL-5, IL-6, IL-9, tumor necrosis factor-alpha, macrophage colony-stimulating factor, transforming growth factor-beta, and, less frequently, IL-4 and granulocyte colony-stimulating factor. These cytokines may be responsible for the increased cellular reaction and fibrosis observed in tissues involved by HD and for the immunosuppression in patients with HD. In contrast to Hodgkin's-Reed-Sternberg cells, most non-HD lymphoma cells do not produce cytokines in excess amounts. Exceptions include T-cell-rich B-cell lymphoma (IL-4), angioimmunoblastic lymphadenopathy-like T-cell lymphoma with plasmacytosis and hypergammaglobulinemia (IL-6), anaplastic large-cell lymphoma (IL-9), polymorphic immunocytoma (IL-6), and immunoblastic lymphoma (IBL) (IL-6). Some cytokines are involved in the unique cellular reactions in each of these types of lymphoma. For example, IL-4 is responsible for the T-cell reaction in T-cell-rich B-cell lymphoma, while IL-6 is accountable for the plasma cell reaction in angioimmunoblastic lymphadenopathy-type T-cell lymphoma. Others may be directly involved in the tumor cell growth or differentiation. For instance, IL-9 may be important for the autocrine proliferation of anaplastic large cell lymphoma, whereas IL-6 is essential for plasmacytoid differentiation in polymorphic immunocytoma. Further studies of the roles of cytokines in lymphomas may lead to major advances in the understanding of the molecular processes involved in the histopathogenesis of malignant lymphomas. Elucidation of the autocrine or paracrine function of cytokines also may lead to new approaches to a rational intervention in these disease processes.
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PMID:Cytokines in malignant lymphomas: review and prospective evaluation. 840 14

Introduction and expression of the proto-oncogene bcl-2 (B-cell lymphoma/leukemia 2) has been shown to extend the survival of certain hematopoietic cell lines after growth factor deprivation, by blocking apoptosis or programmed cell death. We investigated the effect of bcl-2 expression on cellular sensitivity to lysis by tumor necrosis factor (TNF), a cytokine capable of inducing apoptosis in several tumor cell lines. Introduction of the human bcl-2 gene in the highly TNF-sensitive L929 mouse fibrosarcoma cell line did not result in altered TNF sensitivity. Likewise, NIH3T3 and REF cells, which are resistant to TNF cytotoxicity but become TNF sensitive upon cotreatment with actinomycin D or upon expression of the adenovirus E1A gene, did not show altered TNF sensitivity upon bcl-2 transfection. Despite constitutive expression of the endogenous bcl-2 gene, human MCF7 breast carcinoma cells, as well as HL60 promyelocytic leukemia and U937 histiocytic lymphoma cell lines were found to be TNF sensitive. bcl-2-overexpressing derivatives of these cell lines did not acquire reduced TNF sensitivity and still exhibited the characteristic pattern of internucleosomal DNA fragmentation of TNF-induced apoptosis. Moreover, bcl-2 expression in the interleukin 3 (IL-3)-dependent myeloid cell line 32D protected these cells from apoptosis resulting from growth factor deprivation, but not from apoptosis induced by TNF. These data clearly establish the absence of a correlation between bcl-2 gene expression and cellular sensitivity to TNF-induced cell lysis. These findings are discussed in the context of the hypothesis of different pathways for induction of apoptosis, only some of which are affected by bcl-2 expression.
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PMID:Effect of bcl-2 proto-oncogene expression on cellular sensitivity to tumor necrosis factor-mediated cytotoxicity. 845 35

Interleukin (IL)-1 alpha, IL-1 beta, tumor necrosis factor (TNF) alpha, and IL-6 are the most important triggers in the response of the immune system to infection and neoplasia. We examined the histochemical distribution of cytokine-possessing cells in neoplastic lymph nodes of 68 malignant lymphomas. The HLA-DR positive interdigitating reticulum cells (IRCs), histiocytes/macrophages (H/Ms) and epithelioid histiocytes with these cytokines were frequently encountered in Hodgkin's disease, B cell lymphoma of lymphoplasmacytic/cytoid, centroblastic and immunoblastic types, and T cell lymphoma of Lennert's and anaplastic large cell types. In almost all cases of B cell lymphoma of chronic lymphocytic leukemia, centrocytic, follicular centroblastic/centrocytic, Burkitt's types and T cell lymphoma of lymphoblastic, angioimmunoblastic lymphadenopathy and pleomorphic types, the cytokine-possessing cells were rarely or occasionally present. These lymphomas with less cytokines had also few or occasionally encountered IRCs, while H/Ms were frequently or occasionally present. Well-developed dendritic reticulum cells in some types of lymphoma had few cytokines. The population of cytokine-possessing cells was related with histologic type of lymphoma and the volume of IRCs. The IRCs might act as an important initiator of reactive cells against tumor cells. In addition, neoplastic T cells influenced the cytokines' possession of IRCs and H/Ms. Although lacunar, Hodgkin's and Reed-Sternberg cells in Hodgkin's disease and the neoplastic cells in peripheral T cell lymphoma showed weak positive reaction of TNF alpha in one third of the cases, lymphoma cells in the majority might have few cytokines, especially IL-1s and IL-6.
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PMID:Cytokine (interleukin-1 alpha, interleukin-1 beta, tumor necrosis factor alpha, and interleukin-6)-possessing cells in lymph nodes of malignant lymphoma. 851 12

The changes of phospholipase D (PLD) activity were investigated during the courses of apoptotic process induced by tumor necrosis factor (TNF)-alpha or anti-Fas/Apo1 antibody in human premyelocyte HL-60 and murine B cell lymphoma A20 cells. The treatment of recombinant TNF-alpha to HL-60 cells resulted in the increased PLD activity as determined by the phosphatidylethanol formation in the presence of 1% ethanol. The enhancement of PLD activity was also observed in the anti-Fas/Apo1 monoclonal antibody-treated A20 cells. However, the activity of PLD was maximized when HL-60 and A20 cells were treated with either TNF-alpha or anti-Fas/Apo1 monoclonal antibody for 6 h. Both TNF-alpha and anti-Fas/Apo1 monoclonal antibody increased PLD activity in a dose-dependent manner up to 200 U/ml and 200 ng/ml, respectively. When the intracellular activity of protein kinase C (PKC) was interrupted by treatment of calphostin-C, both the PLD activation and the apoptosis induced by TNF-alpha and anti-Fas/Apo1 monoclonal antibody appeared to be inhibited. Since PKC is reported to activate PLD, the results indicate that the intracellular signaling cascade via PLD may play a role in the induction of apoptosis induced by TNF-alpha and anti-Fas/Apo1 monoclonal antibody.
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PMID:Changes of phospholipase D activity in TNF-alpha and anti-Fas/Apo1 monoclonal antibody induced apoptosis in HL-60 and A20 cells. 987 18


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