Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q06643 (non-Hodgkin's lymphoma)
 11,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cytokine secreted by a human hybrid B cell line (STS 25) obtained by fusion of the B lymphoblastoid cell line WI-L2-729-HF2 with neoplastic B cells from a patient with B cell non-Hodgkin's lymphoma (B-NHL) was characterized as IL-1 alpha. STS 25 cells express the idiotypic (Id+) immunoglobulin (Ig) specific for the neoplastic B cells of the B-NHL patient. STS 25 cells are weakly positive for surface mu delta kappa and in addition express the surface markers CD19, CD20, CD23, HLA class I and II, and the 4F2 activation antigen. STS 25 cells are also Epstein-Barr nuclear antigen positive but do not secrete viral particles. Serum-free culture supernatant from STS 25 cells (STS 25 SUP) does not show activity in assays for interleukin-2 (IL-2), -4 (IL-4), -6 (IL-6), interferon or tumor necrosis factor, but is active in the thymocyte costimulation assay and the D10.G4.1 T helper clone proliferation assay for interleukin-1 (IL-1). The IL-1 character of the STS 25 SUP activity was confirmed in inhibition studies with three different poly- or monoclonal anti-IL-1 antibodies (31, 88, and 94% inhibition in thymocyte costimulation assay, respectively). Furthermore, complete blocking of D10.G4.1 cell proliferation mediated by STS 25 SUP was observed by including anti-IL-1 alpha specific antibody in the assay, whereas anti-IL-1 beta antibody had no effect. These results indicate that this STS 25 SUP activity can be attributed to the presence of IL-1 alpha in the supernatant. Northern blot analysis of total STS 25 cellular RNA using IL-1 alpha or IL-1 beta specific probes revealed the constitutive expression of IL-1 alpha messenger RNA by STS 25 cells. In contrast, no IL-1 beta message was detectable, not even after treatment of the cells with phorbol ester or cycloheximide, which resulted in approximately 5-fold enhancement of IL-1 alpha mRNA expression. Binding studies with radiolabeled recombinant (r) IL-1 alpha indicated the presence of high numbers of IL-1 receptors on STS 25 cells (1,170 per cell, Kd = 392 pM). Although both IL-1 alpha and IL-1 beta bound to these IL-1 receptors, no indication was found for IL-1 mediated regulation of STS 25 cell growth.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Functional and molecular characterization of B cell line derived interleukin-1 alpha. 278 53

Several cytokines including gamma-interferon, tumor necrosis factor alpha, interleukin 1 beta (IL-1 beta), and interleukin 6 (IL-6) are pyrogenic and can inhibit lipogenic processes. Because patients with lymphoma often suffer from fever, weight loss, and night sweats (B symptoms), the etiology of which is unknown, the authors investigated serum levels of these cytokines in normal volunteers and in patients with Hodgkin's and non-Hodgkin's lymphoma. Sixty serum samples from patients with Hodgkin's disease (28 patients) or non-Hodgkin's lymphoma (32 patients), as well as 20 samples from normal volunteers, were collected. The majority of patients had advanced (Stage III or IV) or relapsed disease. The assay for gamma-interferon was a specific and sensitive radioimmunoassay (lower limit of detection = 0.1 unit/ml); the assays for tumor necrosis factor alpha, IL-1 beta, and IL-6 were enzyme-linked immunoassays with lower limits of sensitivity of 10 pg/ml, 20 pg/ml, and 22 pg/ml, respectively. There were no statistically significant differences in gamma-interferon, tumor necrosis factor alpha, or IL-1 beta levels between lymphoma patients and normal subjects. In contrast, 20 of 57 patients (35%) with lymphoma as compared with 0 of 19 normal volunteers (0%) had detectable serum IL-6 levels (P < 0.005, chi 2 test). Interestingly, 17 of 29 lymphoma patients with B symptoms (59%) as opposed to 3 of 28 lymphoma patients without B symptoms (11%) had detectable serum IL-6 levels (P < 0.001, chi 2 test); the median IL-6 level was 28.9 pg/ml (B symptoms present) versus undetectable (no B symptoms) (P < 0.005, Mann-Whitney U test). Analyzing Hodgkin's and non-Hodgkin's lymphoma groups separately revealed similar results. IL-6 levels showed no significant correlation with time from diagnosis, beta 2-microglobulin, or lactate dehydrogenase levels. However, analysis by the method of Kaplan and Meir demonstrated that the median survival of Hodgkin's disease patients with detectable IL-6 levels (> or = 22 pg/ml) was 10 mo, whereas the median survival has not been reached at a median follow-up time of 37.5 mo in those patients with lower values (Wilcoxon P value = 0.0012). There were too few patients in each subset of non-Hodgkin's lymphoma to determine the correlation between IL-6 and survival but, considered as a single group, a statistically significant correlation was not found.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Serum interleukin 6 levels are elevated in lymphoma patients and correlate with survival in advanced Hodgkin's disease and with B symptoms. 848 13

The use of ex vivo expanded CD34-selected hematopoietic progenitor cells (HPCs) for autologous stem cell support or gene therapy is a major area of research and is likely to increase in the future. At present, little is known about the fate of contaminating malignant cells during ex vivo expansion of CD34-selected HPCs. We established a competitive polymerase chain reaction (PCR) titration assay to determine the number of residual lymphoma cells before and after selection and ex vivo expansion of CD34-selected HPCs in patients with t(14; 18) translocation carrying non-Hodgkin's lymphoma. Seven bone marrow (BM) and 2 mobilized peripheral blood progenitor cell samples from 8 patients without histologic BM involvement at the time of the harvest were analyzed by competitive PCR titration assay and determined to contain between < or = 10 and 4,000 lymphoma cells/ 10(6) mononuclear cells (MNCs). Immunoadsorption enriched CD34+ cells from a mean of 5% (range, 1% to 9%) to a mean of 88% (range, 76% to 94%) of MNCs and resulted in a 1 to 4 log depletion of contaminating tumor cells. Two HPC samples became PCR negative after CD34 selection, whereas 7 samples still contained < or = 10 to 200 residual lymphoma cells/10(5) MNCs. CD34-selected cells were consecutively expanded in suspension culture in the presence of stem cell factor, interleukin-1 beta (IL-1 beta), IL-3, and IL-6. The mean increase of cells was 13-fold (range, 4- to 22-fold) at day 7 and 65-fold (range, 43- to 110-fold) at day 14 of culture. Expansion resulted predominantly in myelomonocytic differentiation, whereas B-cell antigen-expressing cells became undetectable. Six of the seven PCR-positive CD34-selected samples became PCR-negative for the t(14; 18) translocation at day 7 and/or 14 of expansion. One PCR-positive and one PCR-negative CD34-selected sample were PCR-positive after ex vivo expansion, but the number of residual lymphoma cells remained at the limit of detection. We conclude that CD34-selection does not eliminate contaminating lymphoma cells in the majority of t(14; 18)+ HPC harvests. However, during ex vivo expansion of CD34-selected HPCs, residual t(14; 18)+ lymphoma cells do not proliferate and become undetectable by PCR in the majority of cases.
 ...
PMID:Fate of contaminating t(14; 18)+ lymphoma cells during ex vivo expansion of CD34-selected hematopoietic progenitor cells. 887 17

Endogenous cytokines are aberrantly produced in many cancers, and serve as autocrine growth factors or indicators in immune response to the tumors. Hence, cytokine deregulation is likely to participate in the development or evolution of the malignant process. Over the last few years, endogenous cytokine levels have been correlated with phenotypic manifestations of cancer and with prognosis. For instance, serum IL-6 levels are elevated in both relapsed and newly-diagnosed Hodgkin's and non-Hodgkin's lymphoma, and these levels correlate with established prognostic features. Furthermore, in diffuse large cell lymphoma, serum IL-6 level is an independent prognostic variable for both complete remission and failure-free survival. Serum IL-10 levels are also elevated in lymphoid malignancies and predict outcome. In some cases, it may be that the balance between endogenous cytokine agonists and antagonists is disrupted. For instance, in chronic myelogenous leukemia, high cellular (leukocyte) levels of IL-1 beta and low levels of IL-1 receptor antagonist (IL-1RA) are seen in advanced disease and correlate with reduced survival. The molecular mechanisms underlying cytokine deregulation are now being investigated, with preliminary data suggesting heterogeneous genetic driving forces, including oncogene aberrations and viral infection.
 ...
PMID:Cytokine deregulation in cancer. 1176 63