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

Chemoattractants, including chemokines such as interleukin 8 (IL-8) and related proteins, activate leucocytes via seven-transmembrane-domain G-protein-coupled receptors. A cDNA for a novel receptor of this kind consisting of 327 amino acids was isolated from a human blood monocyte cDNA library. The polypeptide, termed monocyte-derived receptor 15 (MDR15), is an alternative form of the Burkitt's lymphoma receptor 1 (BLR1) encoded by a human Burkitt's lymphoma cDNA [Dobner, Wolf, Emrich and Lipp (1992) Eur. J. Immunol. 22, 2795-2799]. MDR15 and BLR1 cDNAs differ in the 5' region, where the open reading frame of MDR15 is shorter by 45 codons. Southern-blot analysis indicates that the two transcripts for MDR15 and BLR1 are encoded by the same gene. Northern-blot analysis using a probe that hybridizes with both mRNAs demonstrated high-level expression in chronic B-lymphoid leukaemia and non-Hodgkin's lymphoma cells and, to a lesser extent, peripheral blood monocytes and lymphocytes. Reverse transcription-PCR studies with MDR15- and BLR1-specific primers showed similar levels of transcripts for both receptors in RNA that was positive in Northern-blot analysis. MDR15 and BLR1 have high structural similarity to receptors for human IL-8 (about 40% amino acid identity) and other chemokines. However, none of a series of radiolabelled chemokines (IL-8, NAP-2, GRO alpha, PF4, IP10, MCP-1, MCP-2, MCP-3, I-309, RANTES and MIP-1 alpha) and other ligands (C3a and leukotriene B4) bound to Jurkat transfectants that stably expressed either MDR15 or BLR1 mRNA. The fact that MDR15 and BLR1 are expressed on leucocytes and show marked sequence similarity to chemokine receptors suggests the existence of as yet unidentified chemokines. Alternative transcript formation affecting the 5'-terminal part of the coding region may be a way to modify ligand-binding selectivity.
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PMID:Sequence variation of a novel heptahelical leucocyte receptor through alternative transcript formation. 763 92

In extensive preclinical testing, a CD3 x CD19 bispecific antibody (BsAb) induced killing of malignant B cells by resting T cells even in an autologous situation. In a 14 day clonogenic assay using a CD19+ pre-B cell line (REH), BsAb required repeated administration together with IL-2 to achieve a 5 log kill by resting peripheral blood T cells. Intravenously administered BsAb in an intrapatient dose escalation study of 3 patients with B cell non-Hodgkin's lymphoma showed limited toxicity (WHO grade II fever and chills) due to tumor necrosis factor-alpha (TNF-alpha) release by T cells. Pharmacokinetics with 2.5 mg BsAb showed peak levels of 200-300 micrograms/ml and a t1/2 of 10.5 h. The next patient, with chronic lymphocytic leukemia (CLL), received 0.6 mg BsAb/m2 as an i.v. infusion preceded by 1 MU IL-2/m2 s.c. Improved T cell activation was noted, as indicated by an increase in IFN-gamma, IL-6, IL-8, and IL-10, in addition to high TNF-alpha increases. TNF-alpha increases were highest on the first day. Toxicity remained restricted to grade II fever and chills, observed every day after the infusion of BsAb. No clear clinical effects were seen in this chemotherapy-resistant CLL patient with a high tumor burden. If subsequent patients also show limited toxicity, treatment of patients with a lower tumor load seems to be warranted to evaluate the efficacy of CD3 x CD19 BsAb therapy.
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PMID:Clinical experience with CD3 x CD19 bispecific antibodies in patients with B cell malignancies. 858 81

Cytokines play an important role in granuloma formation, but the extent that cytokine profiles are similar in different granulomatous diseases and whether differences in the histopathologic features of the granulomatous response results from differences in cytokine production have not been evaluated. To investigate these questions, we used RT-PCR to quantify the expression of mRNAs coding for 16 cytokines in granulomatous lymph nodes from patients with tuberculosis and sarcoidosis and from control tissues, and we sought correlations between the level of expression of these cytokines and the histopathologic features of the granulomas. Expression of mRNAs coding for a number of cytokines (IL-1beta, IFN-gamma, TNF-alpha, granulocyte-macrophage (GM)-CSF, IL-12 (p40), and lymphotoxin-beta) was increased in tuberculous and sarcoid granulomas compared with that of control tissues. All sarcoid granulomas were shown to express a Th1 pattern of cytokine mRNAs, while tuberculous lymph nodes expressed either a Th1 or a Th0 profile. GM-CSF and lymphotoxin-beta mRNAs were more abundant in sarcoid than in tuberculous granulomas, whereas IL-8 mRNA was strongly expressed only in tuberculous lymph nodes. Strong expression of GM-CSF, TNF-alpha, and IL-8 by granulomas was shown to be correlated, respectively, with the presence of florid granulomatous lesions, the absence of central necrosis, and the presence of neutrophil infiltration. These results demonstrate that the formation of tuberculous and sarcoid granulomas in humans is associated with the expression of characteristic cytokine profiles and indicate that the expression of certain cytokines is associated with the development of specific pathologic features in the resulting granulomas.
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PMID:Cytokine patterns in tuberculous and sarcoid granulomas: correlations with histopathologic features of the granulomatous response. 930 Jul 29

Treatment with rituximab, a chimaeric anti-CD20 monoclonal antibody, can be associated with moderate to severe first-dose side-effects, notably in patients with high numbers of circulating tumour cells. The aim of this study was to elucidate the mechanism of these side-effects. At multiple early time points during the first infusion of rituximab, complement activation products (C3b/c and C4b/c) and cytokines [tumour necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6) and IL-8] were measured in five relapsed low-grade non-Hodgkin's lymphoma (NHL) patients. Infusion of rituximab induced rapid complement activation, preceding the release of TNF-alpha, IL-6 and IL-8. Although the study group was small, the level of complement activation appeared to be correlated both with the number of circulating B cells prior to the infusion (r = 0.85; P = 0.07) and with the severity of the side-effects. We conclude that complement plays a pivotal role in the pathogenesis of side-effects of rituximab treatment. As complement activation can not be prevented by corticosteroids, it might be relevant to study the possible role of complement inhibitors during the first administration of rituximab.
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PMID:Complement activation plays a key role in the side-effects of rituximab treatment. 1184 13

Although Fas (APO-1/CD95) is expressed ubiquitously and induces cell death, it is also known to mediate other responses such as inflammation and angiogenesis in vivo. Previously, we have reported that Fas ligation induces selective expression of chemokines (IL-8 and MCP-1) in human astroglioma cells in vitro. In this study, we investigated whether Fas ligation can induce expression of other cytokines. Expression of IL-1alpha, IL-1beta, IL-6, IL-10, IL-12, IFN-beta, IFN-gamma, LT-beta, TGF-beta, TNF-a and TNF-beta mRNA levels in CRT-MG human astroglioma cells upon Fas ligation was investigated using RNase protection assay (RPA). We found that IL-6 mRNA is selectively induced upon Fas ligation, and IL-6 mRNA and protein expression was further investigated using single probe RPA and ELISA. To investigate the in vivo expression of IL-6, human brain specimens were homogenized and ELISA was performed for IL-6 expression. Herein, we demonstrate that: (1) Among these cytokines, only IL-6 was induced upon Fas ligation in a dose- and time-dependent manner; (2) A selective p38 MAP kinase inhibitor, SB202190, and a MEK inhibitor, U0126, suppressed induction of IL-6 mRNA and protein expression by Fas ligation; and (3) Glioblastoma multiforme samples (n = 11) contain significantly higher levels of IL-6 compared to those of control brains (n = 5), which correlate with increased levels of Fas. These results suggest that the Fas-FasL system may play a role in the regulation of tumor growth and survival by inducing the pleiotropic cytokine IL-6.
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PMID:Fas engagement increases expression of interleukin-6 in human glioma cells. 1194 22

Tumor angiogenesis plays a significant role in cancer growth and metastasis. This complex process is influenced by a variety of angiogenic factors. Elevated serum levels or high expression of some of these factors have been shown to correlate with stage and prognosis in certain human malignancies. This has been demonstrated most consistently for vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). We tried to establish, whether pre-treatment serum levels of the angiogenic factors VEGF, bFGF, interleukin 8 (IL-8) and Flt3 ligand (Flt3L) correlate with prognostic variables in 30 patients with primary gastro-intestinal non-Hodgkin's lymphoma. Our results suggest that higher pretreatment serum levels of IL-8 and Flt3L are associated with higher stage (>or= II) and high grade, respectively. Elevated pretreatment serum levels of VEGF and bFGF were not associated with advanced disease characteristics and carried no prognostic information.
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PMID:Interleukin 8 and Flt3 ligand as markers of advanced disease in primary gastrointestinal non-Hodgkin's lymphoma. 1195 21

The conditioning regimens for autologous SCT (auto-SCT) lead to impairment of the immune system and concomitant increase in susceptibility to infections. We studied the recovery of cellular immunity by in vitro analysis of T-cell proliferation and cytokine production profiles during the first 15 months after auto-SCT in patients with multiple myeloma and non-Hodgkin's lymphoma. PBMC were collected at 6, 9 and 15 months after transplantation and stimulated with a combination of CD2 and CD28 monoclonal antibodies, with PHA or with tetanus toxoid as recall antigen. A multiplex enzyme linked immunoassay was used to determine levels of Th1 cytokines IL-2, IFN-gamma and tumour-necrosis factor-alpha (TNF-alpha), Th2 cytokines IL-4, IL-5 and IL-13, the regulatory cytokine IL-10 and the proinflammatory cytokines IL-1alpha, IL-1beta, IL-6 and the chemokine IL-8. T-cell proliferation progressively increased from 6 to 15 months after auto-SCT. Overall, cytokine production increased after auto-SCT. Production of Th2 cytokines IL-5 and IL-13 was superior to production of Th1 cytokines IFN-gamma and TNF-alpha. We hypothesize that prolonged impairment of IFN-gamma production might contribute to the relatively high incidence of viral infections after auto-SCT.
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PMID:Development of T cell-mediated immunity after autologous stem cell transplantation: prolonged impairment of antigen-stimulated production of gamma-interferon. 1756 37

Angiogenesis plays an important role in many types of cancer. Interleukin-8 (IL-8) is known to be a pro-inflammatory and pro-angiogenic cytokine, and IL-8 has been reported to be associated with tumor progression, prognosis and survival in several types of cancers. However, the role of IL-8 in non-Hodgkin's lymphoma (NHL) has not been fully determined. Here, we evaluated the usefulness of measuring serum and urine IL-8 levels in patients with NHL. We developed reference intervals for serum and urine IL-8 level in 131 control individuals. We measured serum IL-8 and urine IL-8 levels in patients with NHL, and we compared the concentrations with those of control individuals. The reference intervals for serum IL-8 and urine IL-8 corrected by creatinine (Cr) were 15.9-430.3 pg/mL and 0.0-28.4 pg/mg Cr, respectively. The concentrations of urine IL-8/Cr were significantly higher in patients than in controls (48.9+/-194.4 vs. 5.2+/-13.8 pg/mg Cr, P<0.001). However, there were no significant differences in serum IL-8 concentrations between NHL patients and controls (159.2+/-40.4 vs. 99.6+/-107.1 pg/mL; P=0.099). Receiver operating characteristic (ROC) analysis gave 0.83 and 0.43 ROC area values for urine IL-8/Cr and serum IL-8, respectively. There was no correlation between the serum and urine concentrations of IL-8 and clinical variables, the only exception being the international prognostic index (IPI), which showed a marginal correlation with urine IL-8/Cr levels (P=0.07). This study indicated that urine IL-8/Cr levels might be useful as a diagnostic marker of NHL.
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PMID:Serum and urine levels of interleukin-8 in patients with non-Hodgkin's lymphoma. 1850 45

Antiangiogenic drugs are currently tested in haematological malignancies. As these drugs target different angiogenic regulators, and as cancers are inherently heterogeneous, a detailed characterization of angiogenesis in individual cancers is needed. Hence, we measured bone marrow microvessel density (MVD), plasma concentrations of eight angiogenesis-related parameters and the expression in blood mononuclear cells of 40 angiogenesis-related mRNAs in 93 patients with haematological neoplasias (acute myeloid leukaemia; chronic lymphatic leukaemia; multiple myeloma (MM); or non-Hodgkin's lymphoma (NHL)) before start and after completion of cancer therapy. Compared with healthy individuals, the patients had significantly increased bone marrow MVD, especially patients with advanced stage disease. A novel finding was that patients with NHL also had increased bone marrow MVD. The plasma levels of vascular endothelial growth factor (VEGF), interleukin (IL)-6 and IL-8 were significantly increased. VEGF levels were highest in those who did not achieve complete remission after cancer therapy. The mRNA expression of IL-8 was upregulated 15-fold. Our data show that patients with haematological malignancies have increased bone marrow MVD; hence, supporting the notion that bone marrow angiogenesis plays a role in the pathogenesis and progression of these cancers. VEGF, IL-6 and IL-8 seem to contribute to the malignant phenotype.
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PMID:Increased bone marrow microvascular density in haematological malignancies is associated with differential regulation of angiogenic factors. 1880 Jan 45

Donor lymphocyte infusions (DLIs) after allo-SCT displayed limited use in CLL and highly malignant non-Hodgkin's lymphoma (NHL). Here we studied whether Bi20 (FBTA05), a novel trifunctional bispecific antibody targeting CD20 on lymphoma cells and CD3 on T cells, could induce GVL responses in combination with DLI or mobilized PBSCT after allogeneic transplantation in these diseases. Six patients (three cases with p53-mutated CLL and three with high-grade NHL (HG-NHL)) refractory to standard therapy were treated with escalating doses of Bi20 (range 10-2000 microg) followed by DLI or SCT. Thereby, all CLL patients showed a prompt but transient clinical and hematological response. In one patient with HG-NHL, we observed a halt in progression for almost 4 months. Side effects (fever, chills and bone pain) were tolerable and appeared at antibody dose levels between 40 and 200 microg. The cytokine profile was characterized by transient increases of IL-6, IL-8 and IL-10. Neither human anti-mouse antibodies nor GVHD developed, allowing repeated treatment courses. In summary, the trifunctional antibody Bi20 induced prompt antitumor responses in extensively pretreated, p53-mutated alemtuzumab and rituximab refractory patients indicating its therapeutic potential.
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PMID:Immunotherapy of recurrent B-cell malignancies after allo-SCT with Bi20 (FBTA05), a trifunctional anti-CD3 x anti-CD20 antibody and donor lymphocyte infusion. 1885 12


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