Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0019829 (Hodgkin's disease)
30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The receptor for human interleukin-9 (hIL-9) might be a target for selective immunotherapy. It is expressed on a variety of malignant cells, including Hodgkin's lymphoma, non-Hodgkin lymphoma and acute myeloid leukemia (AML). We therefore constructed a new chimeric toxin by fusing hIL-9-cDNA to modified Pseudomonas aeruginosa exotoxin A (ETA'). The binding properties of the new recombinant protein, rhIL-9-ETA', were assessed on different cell lines expressing the hIL-9 receptor. The antitumor potency of rhIL-9-ETA' was evaluated against the Hodgkin-derived cell lines L540Cy, KM-H2 and L1236, the Burkitt lymphoma cell line Daudi, the erythroleukemia cell line K562, and the mastocytoma cell line P815-hIL9R, transfected with hIL-9 receptor cDNA. Recombinant hIL-9-ETA' exhibited potent specific cytotoxic effects against P815-hIL9R, K562 and L1236 cells, inhibiting protein synthesis by 50% (IC50) at concentrations of 0.05, 0.58 and 3 micrograms/ml respectively. The cytotoxic effect was abrogated after addition of polyclonal antibodies against the human IL-9. rhIL-9-ETA' might be of potential use against hIL-9R-expressing malignancies.
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PMID:A deletion mutant of Pseudomonas exotoxin-A fused to recombinant human interleukin-9 (rhIL-9-ETA') shows specific cytotoxicity against IL-9-receptor-expressing cell lines. 938 98

The Epstein-Barr virus (EBV) was isolated 40 years ago from cultures of Burkitt lymphoma cells (BL). The tumor was encountered in Africa and exhibited characteristical geographical, clinical and pathological features. Serological studies revealed that the virus is ubiquitous in humans. The primary infection is often accompanied by the syndrome of acute infectious mononucleosis (IM). It can induce malignant proliferation of B lymphocytes in conditions of immunodeficiency. EBV can immortalize B lymphocytes in culture. These cells carry the virus as episomes and express 9 virally encoded proteins. Their immunological recognition constitutes the surveillance which is responsible for the healthy virus carrier state. The main virus reservoir is represented by a low number of resting B lymphocyte which contain the viral genome but do not express its transformation proteins. The viral genome is detectable in all African BLs, in variable proportions of nasopharyngeal carcinoma, Hodgkin's disease, T cell lymphoma, lymphoepithelial like carcinoma, gastric carcinoma and leiomyosarcoma cases. The role of EBV in the genesis of these tumors is unknown.
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PMID:The complexity of the Epstein-Barr virus infection in humans. 955 13

Three cases of (3;13)(q27;q14) translocation observed in different histological types of non-Hodgkin lymphomas (NHLs) are reported here. This new recurring translocation in NHL was secondary in at least two of the patients because it was associated with another specific change [i.e., t(8;14) (q24;q32) in Burkitt lymphoma and t(14;18)(q32;q21) in typical follicular lymphoma]. In two of the cases for which molecular analysis was performed, a rearrangement of the LAZ-3/BCK-6 gene was found.
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PMID:Translocation (3;13)(q27;q14): a nonrandom and probably secondary structural change in non-Hodgkin lymphomas. 961 13

Epstein-Barr virus (EBV) has been associated with several malignant processes in man, most notably Burkitt lymphoma in previously healthy individuals and lesions resembling large cell non-Hodgkin lymphomas in organ transplant recipients. Mice with the severe combined immunodeficiency phenotype (SCID mice) are exquisitely susceptible to the development of EBV-associated lymphoproliferative lesions following the intraperitoneal (ip) inoculation of EBV-infected human lymphocytes. Recently, we reported that EBV-infected marmoset lymphocytes do not form lymphomas in SCID mice following ip injection, while human lymphocytes infected with the same EBV strains do. On the assumption that the EBV-infected marmoset cells were lacking a factor necessary for tumor formation, we transfected a plasmid containing c-myc into EBV-infected marmoset cells (B95-8, FF41, and W91 cells). Despite expression of the c-myc protein as determined by immunoblot and flow cytometry when probed with a monoclonal antibody, no increase over baseline lesion development was seen in SCID mice inoculated with 5 x 10(6) c-myc-expressing marmoset lymphoblastoid cells. Thus, cells that express c-myc and harbor EBV are not sufficient to form lymphomas in certain immunocompromised hosts.
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PMID:Epstein-Barr virus-infected marmoset cells transfected with c-myc do not form lymphomas in mice with severe combined immunodeficiency. 971 30

The pathogenesis of AIDS-related non-Hodgkin's lymphomas (AIDS-NHL) involves accumulation of genetic lesions, stimulation and selection by antigen, as well as infection by viruses. Deregulation of cytokine loops has also been proposed to contribute to AIDS-NHL development, although data are available only for a limited number of cytokines. In this study we have utilized a panel of AIDS-NHL cell lines to investigate in detail the pattern of tumour expression and production of a wide spectrum of cytokines. The cytokines investigated included interleukin (IL)-1alpha, IL-1beta, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-13, TNF alpha, TNF beta, IFN gamma, TGF beta2, G-CSF, GM-CSF and SCF. The AIDS-NHL cell lines utilized were representative of both AIDS-related Burkitt lymphoma (AIDS-BL) and AIDS-related body cavity-based lymphoma (AIDS-BCBL). Overall, AIDS-NHL were found to produce IL-6, IL-10 and TNF beta, although with different patterns depending upon the biological features of the tumour. Production of high levels of IL10 preferentially associated with Epstein-Barr virus (EBV) positive AIDS-BL and AIDS-BCBL, although lower levels of the cytokine were also detectable among EBV-negative AIDS-BL. Production of IL-6 was restricted to EBV-positive AIDS-BL and AIDS-BCBL, whereas it was absent among EBV-negative AIDS-BL. Production of TNF beta clustered with AIDS-BL, whereas this was absent among AIDS-BCBL. These results define that the pattern of cytokine expression of AIDS-NHL depends upon the biological features of the tumour and may have implications for the pathogenesis of these disorders.
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PMID:Patterns of cytokine expression in AIDS-related non-Hodgkin's lymphoma. 979 1

The clinical and pathological features of acquired immune deficiency syndrome (AIDS)-related lymphomas, including their relationship with other viruses, such as Epstein-Barr virus (EBV) and human herpes virus-8 (HHV8), have been the subject of several studies from North America and Europe. No consistent data have been reported in Africa, where AIDS runs an epidemiological and clinical course different from that observed in Western countries. We retrospectively evaluated the presence of human immunodeficiency virus (HIV), HHV8, and EBV in 146 cases of malignant lymphomas collected in Kenya (Equatorial Africa), with the use of polymerase chain reaction (PCR) and in situ hybridization (ISH). The PCR technique confirmed HIV infection in 16 HIV-seropositive subjects (11%) and showed the presence of HIV sequences in five additional cases (3%) in which the occurrence of lymphoma was the only clinical manifestation. Our findings suggest that AIDS-related lymphomas are not pathogenetically homogenous, and different mechanisms may contribute to lymphomagenesis in these severely immunocompromised patients. In our series, no association of Hodgkin's disease (HD) with HIV infection could be shown. Among non-HIV-related lymphomas, EBV was present in 94% of Burkitt lymphoma (BL) occurring in patients younger than 15 years of age, in 87% of HD independently of age, sex, and histological types, in 60% of anaplastic large cell lymphoma (ALCL), and to a lesser extent (13%) in large B-cell lymphoma (LBCL) cases. Only one tumor, a case of HD, showed HHV8 by PCR.
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PMID:HIV-associated malignant lymphomas in Kenya (Equatorial Africa) 1053 80

The data of a closed phase I/II trial in patients with resistant Hodgkin's lymphoma indicate promising results using a chemically linked anti-CD25 ricin-A immunotoxin (IT) (RFT5-SMPT-dgA). This IT is based on the high-affinity moab RFT5. Since recombinant DNA technology permits the readier production of large amounts of ITs, we constructed a new RFT5-based fusion toxin [RFT5(scFv)-ETA']. We isolated mRNA from the hybridoma cell line RFT5, synthesized first strand cDNA and performed RT-PCR. Amplified coding regions of the light and heavy chain variable domains were joined together with a synthetic (Gly4-Ser)3 linker. The resulting single chain variable fragment (scFv) was fused to a modified Pseudomonas aeruginosa exotoxin A (ETA') lacking its cell-binding domain I. After IPTG-induced expression in Escherichia coli, the 70 kDa His-tagged fusion protein [RFT5(scFv)-ETA'] was isolated by osmotic shock and sonication under denaturing conditions. The recombinant toxin was purified on a Ni2+-NTA chelating sepharose and eluted with 250 mM imidazole. Pooled protein was renatured, dialyzed and concentrated by precipitation. Binding properties of RFT5(scFv)-ETA' were assessed on the CD25-expressing cell line L540cy by ELISA, immunohistochemistry and FACS analysis. CD25-specific binding was confirmed by immunoprecipitation experiments with recombinant human IL-2 receptor alpha. The in vitro toxicity of the chimeric protein was tested on the Hodgkin-derived cell lines L540cy, L428, L1236, a monocyte cell line U937 and a Burkitt lymphoma cell line BL38. RFT5(scFv)-ETA' inhibited protein biosynthesis of L540cy and L428 cells by 50% at concentrations (IC50) of 18 and 12 ng/ml, respectively. CD25-specific toxicity was confirmed by competitive toxicity assays. These data confirm for the first time binding specificity and toxicity of a recombinant anti-CD25 immunotoxin, against Hodgkin-derived cell lines; its applicability on Hodgkin's lymphoma needs yet to be evaluated in vivo.
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PMID:Construction and in vitro evaluation of RFT5(scFv)-ETA', a new recombinant single-chain immunotoxin with specific cytotoxicity toward CD25+ Hodgkin-derived cell lines. 985 27

Epstein-Barr virus (EBV) causes lymphoproliferative diseases in immunocompromised patients and is associated with endemic Burkitt lymphoma, nasopharyngeal carcinoma and some cases of Hodgkin disease. The latent membrane protein 1 (LMP1) of EBV is a transmembrane protein that is essential for the transformation of B lymphocytes. LMP1-mediated up-regulation of Bcl-2 is thought to be an important element in this process. As an approach to explore novel treatments for EBV-associated lymphomas, we constructed a single-chain antibody (sFv) directed against LMP1 to achieve functional inhibition of this oncoprotein in EBV-transformed B lymphocytes. We demonstrated that intracellular expression of an endoplasmic reticulum (ER)-targeted form of this sFv markedly reduced LMP1 protein levels. We also observed a decrease in intracellular level of this protein which correlated with a marked reduction of Bcl-2 expression in EBV-transformed B lymphocytes. We further demonstrated that anti-LMP1 sFv-mediated reduction of Bcl-2 correlated with increased sensitivity of these cells to drug-induced cell death. Therefore, these data suggest that an anti-LMP1 sFv used in combination with conventional chemotherapy may be useful for gene therapy of EBV-associated lymphomas in immunocompromised patients.
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PMID:Phenotypic knock-out of the latent membrane protein 1 of Epstein-Barr virus by an intracellular single-chain antibody. 993 Mar 17

CD43 expression on B cells is an immunophenotypic feature suggestive of malignancy. In the light of its diagnostic importance, we performed a comprehensive survey of CD43 expression in various types of non-Hodgkin lymphoma (NHL) and determined the frequency of its expression in routinely fixed paraffin-embedded tissues. Tissue sections in 742 cases of NHL, pretreated by the heat-induced epitope retrieval technique, were immunostained using an anti-CD43 antibody. Three categories of CD43 positivity were found: (1) more than 90% of T-cell lymphoma, mantle cell lymphoma, B-cell small lymphocytic lymphoma, and Burkitt lymphoma cases were positive; (2) 20% to 40% of nodal and extranodal marginal zone lymphoma (MZL), diffuse large B-cell lymphoma, Burkitt-like B-cell lymphoma, and lymphoplasmacytoid lymphoma cases were positive; and (3) 0% to 6% of primary splenic MZL and various types of follicular lymphoma cases were positive. Most CD43+ follicular lymphomas were predominantly large cell type with focally diffuse areas; their follicular center cell origin in 4 of 8 cases was supported by the presence of CD10 immunoreactivity and/or t(14;18) fusion gene product. CD43 is frequently detectable in a subset of B-NHL, and, thus, it seems to be a highly sensitive marker for these tumors. CD43 also may be a useful marker for classifying B-cell NHLs by virtue of its differential expression in these tumors.
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PMID:Frequency of CD43 expression in non-Hodgkin lymphoma. A survey of 742 cases and further characterization of rare CD43+ follicular lymphomas. 1019 68

The D-type cyclins, involved in the regulation of G1 progression of the cell cycle, are expressed in a lineage-specific manner. Normal hematopoietic cells express cyclin D2 and/or D3. In order to determine whether their expression pattern changes in lymphoid tumors, we examined cyclin D2 and D3 expression in non-neoplastic and neoplastic lymphoid lesions, using a sensitive immunohistochemical amplification method. Centroblasts in lymphoid follicles of reactive lymph nodes expressed exclusively cyclin D3 and no D2. Interfollicular areas contained scattered cyclin D3 and D2 positive cells. By double staining, cyclin D3 was detected in CD79a positive B cells, CD3 positive T cells and CD68 positive macrophages. Cyclin D2 was present only in CD3 positive T cells. Neoplastic lymphoid lesions included 33 B cell lymphomas, 9 T cell lymphomas and 12 Hodgkin's lymphomas. The B cell lymphomas comprised 9 follicular lymphomas (FL), 1 Burkitt lymphoma (BL), 22 diffuse large cell lymphomas (DL) and 1 chronic lymphocytic leukemia (CLL). All 9 FLs and the single BL expressed exclusively cyclin D3, similarly to germinal center B cells, that represent their cells of origin. Six DLs expressed both cyclin D2 and D3, while 6 expressed only D3. Among the 9 pleomorphic T cell lymphomas, medium and large cell type, 5 expressed cyclin D2. Cyclin D3 was also detected in scattered cells in 4 of 9 cases and was highly expressed in 2 of 9 T cell lymphomas. The majority of Hodgkin's lymphomas expressed both cyclin D2 and D3 in Hodgkin/Reed-Sternberg (HRS) cells. The high frequency of positive cells indicates that both cyclins were expressed in the same cells.
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PMID:Expression of cyclin D2 and D3 in lymphoid lesions. 1022 42


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