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 peroxisome proliferator-activated receptor gamma (PPAR gamma) is a member of the nuclear receptor family that forms heterodimers with retinoid X receptor. These heterodimers bind to DNA and activate the transcription of target genes. Here, we report that the PPAR gamma receptor protein is expressed in primary myeloid and lymphoid leukemias and in lymphoma and myeloma cell lines. In this study, we compared the activity of several PPAR gamma ligands including BRL49653 (rosiglitazone), 15-deoxy-Delta 12,14-prostaglandin J(2), and the novel triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid on leukemia cells. Exposure to these PPAR gamma ligands induced apoptosis in myeloid (U937 and HL-60) and lymphoid (Su-DHL, Sup-M2, Ramos, Raji, Hodgkin's cell lines, and primary chronic lymphocytic leukemia) cells. A similar exposure to these PPAR gamma ligands induced the differentiation of myeloid leukemic cells. A combination of PPAR gamma ligands with a retinoid X receptor agonist (i.e., LG100268) or a retinoic acid receptor agonist (i.e., all trans-retinoic acid) enhanced differentiating and growth-inhibitory effects. 2-Cyano-3,12-dioxooleana-1,9-dien-28-oic acid induced differentiation and apoptosis with much greater potency than the other PPAR gamma ligands in established cell lines and primary chronic lymphocytic leukemia samples. Exposure to 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid induced mitochondrial depolarization and caspase activation, which was associated with apoptosis induction. In Bcl-2-overexpressing chronic lymphocytic leukemia cells, the small-molecule Bcl-2 inhibitor HA14-1 sensitized these cells to 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid-induced apoptosis. These results suggest that PPAR gamma ligation alone and in combination with retinoids holds promise as novel therapy for leukemias by activating the transcriptional activity of target genes that control apoptosis and differentiation in leukemias.
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PMID:Peroxisome proliferator-activated receptor gamma and retinoid X receptor ligands are potent inducers of differentiation and apoptosis in leukemias. 1548 92

We describe successful treatment of a 38-year-old patient with composite lymphoma stage IV(A), who presented with multifocal enlarged lymph nodes. The lymph node histology showed classic morphologic features of Hodgkin's disease, mixed cellularity subtype and follicular B-cell lymphoma. Immunophenotypic analysis showed immunoreactivity for CD20, CD10 and Ki-67 in the malignant small cell population. The areas of Hodgkin's disease demonstrated positive immunoreactivity for CD30 and CD20 in the Hodgkin's cells. Both cell populations were bcl2-oncoprotein positive. Eight courses of dose-escalated BEACOPP were administered. Restaging after chemotherapy showed radiological partial remission, but biopsy confirmed persisting follicular B-cell lymphoma without bone marrow infiltration and no evidence of Hodgkin's disease. He was treated with monoclonal CD 20-antibody (Rituximab) 10 mg/kg weekly for eight consecutive weeks due to marked positivity of CD 20-antigen in follicular lymphoma cells. This treatment was well tolerated and final staging showed complete remission of the composite lymphoma. This patient continues to be in remission 28 months after the end of the treatment. In conclusion, in the very rare case of composite lymphoma a combination of chemotherapy and subsequent immunotherapy might be considered as a promising therapeutic option.
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PMID:Sequential application of chemotherapy and monoclonal CD 20 antibody: successful treatment of advanced composite-lymphoma. 1562 15

Mummified tumour cells in Hodgkin's lymphoma (HL) are a special type of programmed cellular death, which differs from apoptosis in several respects. The common feature with apoptosis is the death of individual tumour cells. The number of mummified cells is many times higher than the number of cells in apoptosis. The authors examined a group of 24 cases of EBV positive and 24 cases of EBV negative HL and assessed the so-called mummification index. The value of the mummification index was 10.4 in EBV positive and 8.2 in EBV negative HL. The difference of values was not marked and therefore it may be concluded that latent EBV infection does not influence the numbers of mummified cells. Using statistical methods (the log-rank test) the authors evaluated survival and differences between groups of EBV positive and EBV negative HL. In the course of 16.6 years no statistically significant difference was found between the two groups of HL. By means of the chi2 individual stages of the disease were compared and no significant differences between groups were recorded. Expression of Bcl-2 protein in tumour cells in HL was small and positivity was not found in mummifying cells. Bcl-2 protein was assessed in 24 EBV positive HL and 37 cases of EBV negative HL. In the first group the authors recorded positive findings in six cases, in the second group in five cases.
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PMID:[Mummified Hodgkin and Reed-Sternberg cells in EBV positive and EBV negative Hodgkin's lymphomas, Bcl-2 positivity and evaluation of survival]. 1563 76

Bcl-2 functions as a key survival factor for lymphocytes and is highly expressed in a majority of non-Hodgkin's lymphomas. The ability of oblimersen sodium (Genasense, previously known as G3139) to target bcl-2 messenger RNA and decrease Bcl-2 protein levels has the potential to enhance the activity of cytotoxic chemotherapy. Pretreatment with oblimersen followed by cyclophosphamide (Cytoxan, Neosar) markedly improved survival relative to single-agent cyclophosphamide in a murine xenograft model. Oblimersen has also enhanced the cytotoxicity of a variety of other agents against non-Hodgkin's lymphoma, including etoposide, rituximab (Rituxan), and alemtuzumab (Campath). An initial phase I study of oblimersen in non-Hodgkin's lymphoma demonstrated modest single-agent activity. Recent reports suggest that oblimersen may add to the activity of R-CHOP (rituximab-cyclophosphamide/doxorubicin/vincristine/prednisone) in previously untreated mantle cell lymphoma and to rituximab alone in a variety of subtypes of relapsed non-Hodgkin's lymphoma. Additional studies in both treatment-naive and relapsed patients will define the role of oblimersen in the treatment of non-Hodgkin's lymphoma.
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PMID:Targeting the proapoptotic factor Bcl-2 in non-Hodgkin's lymphoma. 1565 Nov 74

Oblimersen sodium is an antisense oligonucleotide to the first 6 codons of the B-cell leukemia gene 2 (bcl-2) open reading frame. It prevents the expression of the bcl-2 gene product and leads to apoptosis in cells that express Bcl-2. bcl-2 is one of the major apoptosis regulatory gene families and is found in a variety of low-grade B-cell non-Hodgkin's lymphomas. The in vitro use of oblimersen in Waldenstrom's macroglobulinemia (WM) cell line results in enhanced toxicity when exposed to fludarabine, dexamethasone, or rituximab. Oblimersen should also enhance the cytotoxic effect of chemotherapy in WM. Presented herein are early data on the phase I portion of a phase I/II study of oblimersen in WM to identify the maximum tolerated dose and to evaluate response in patients with symptomatic WM.
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PMID:Early results of a phase I trial of oblimersen sodium for relapsed or refractory Waldenstrom's macroglobulinemia. 1579 66

T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL), a proliferating peripheral B-cell neoplasm, is a morphologic variant of diffuse large B-cell lymphoma (DLBCL), which may be confused with Hodgkin's lymphoma, non-Hodgkin's lymphoma, and reactive lymphadenopathies. Though more recent studies suggested that it might be a distinct clinicopathologic entity and/or a heterogeneous entity with derivation from germinal center B cells, its histogenetic derivation remains controversial. The authors analyzed 30 cases of THRLBCL to further characterize the origin of the neoplastic cells using immunohistochemical and molecular studies for expression of Bcl-6, CD10, and CD138, as well as rearrangements of IgH/bcl-2 genes on paraffin-embedded tissue. Half of the cases (15/30) showed Bcl-6 expression and five cases (19%) showed CD10 expression, but none had CD138 expression (0/20). Only three cases showed coexpression of both Bcl-6 and CD10. Molecular studies performed in 21 cases detected rearrangement of immunoglobulin heavy gene in 18 cases, with none having detectable Bcl-2 gene rearrangement. These data indicate that similar to DLBCL, the cell origin of neoplastic cells in THRLBCL is composed of a heterogeneous group of proliferating peripheral B cells, with only some cases originating from germinal center B cells and others derived from heterogeneous origins. Lack of Bcl-2 gene rearrangements seems to argue against a possible progression from preexisting follicular lymphoma. Thus, the normal counterpart of the neoplastic cells cannot at this time be the sole basis for the subclassification of THRLBCL.
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PMID:T-cell/histiocyte-rich large B-cell lymphoma displays a heterogeneity similar to diffuse large B-cell lymphoma: a clinicopathologic, immunohistochemical, and molecular study of 30 cases. 1589 21

Patients with B non-Hodgkin's Lymphoma (NHL) initially respond to conventional chemotherapy. However, relapses and recurrences occur and the patients develop resistance to further treatment. Immunotherapeutic approaches have been considered in the treatment of such patients. Rituximab (chimeric anti-human CD20 monoclonal antibody) is the first anti-cancer monoclonal antibody approved by the FDA for the treatment of B-NHL. It has been used alone or in combination with chemotherapy, and the clinical response rates have been 50% and greater than 95%, respectively. The in vivo mechanism by which rituximab mediates its effects is not clear, though ADCC, CDC and apoptosis have been suggested and supported by several studies. However, many patients do not respond to rituximab or become refractory to rituximab treatment and the underlying mechanism of unresponsiveness is not known. This review describes various molecular signaling pathways modified by rituximab using in vitro B-NHL cell lines as model systems. The findings demonstrate that rituximab treatment modulates the p38 MAPK, the Raf-1/MEK/ERK1/2 and the NF-kappaB pathways. These modifications induced by rituximab were in large part responsible for the down-regulation of the anti-apoptotic gene products Bcl-2/Bcl-xL and chemosensitization of the drug-resistant B-NHL cell lines to various drug-induced apoptosis. Studies on the development of resistance to rituximab were investigated with rituximab-resistant B-NHL clones derived from rituximab-sensitive B-NHL cell lines. The molecular signaling pathways modified by rituximab revealed several novel intracellular targets whose modification could sensitize both rituximab-sensitive and rituximab-resistant B-NHL to drug-induced apoptosis. These in vitro findings provide new possibilities for improving the clinical effectiveness of rituximab as well as for circumventing its resistance.
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PMID:Rituximab-mediated chemosensitization of AIDS and non-AIDS non-Hodgkin's lymphoma. 1593 40

This study was undertaken to evaluate the clinical significance of the expression of Bcl-2, p53 and LMP-1 in Hodgkin and Reed - Sternberg cells of patients with Hodgkin's lymphoma. The expression of these proteins in pre-treatment tissue biopsy specimens was correlated with presenting clinical features, failure-free survival (FFS) and overall survival (OS) in 83 patients with a confirmed Hodgkin's lymphoma treated in a single institution. HIV-positive patients were excluded. Patients were classified according to the International Prognostic Score (IPS) in low-risk (0 - 2 factors) and high-risk groups. The median age was 41 years (15 - 84), 41% were women, and 93% had advanced-stage disease (IIB - IVB). The expression of Bcl-2, p53 and LMP-1 was not associated with the complete remission rate, FFS or OS. The IPS risk group was the only factor significantly associated with OS. Patients with a high IPS had a lower 5 year OS (43% vs. 79%, P = 0.003). The expression of Bcl-2, p53 and LMP-1 did not add prognostic information to the IPS.
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PMID:The prognostic value of the expression of Bcl-2, p53 and LMP-1 in patients with Hodgkin's lymphoma. 1610 7

Infection with HCV can be associated with B-cell non-Hodgkin lymphoma. Polymerase chain reaction (PCR) amplification assays for Bcl-2/IgH rearrangement were performed on nucleic acids extracted from portal tract inflammatory infiltrates, isolated with laser capture microdissection (LCM), from liver biopsy sections of 16 hepatitis C virus (HCV)-infected patients with and without extrahepatic B cell-related disorders. Results were compared with total DNA extracted from core liver biopsy specimens and from peripheral blood mononuclear cells (PBMCs). We failed to demonstrate specific Bcl-2/IgH amplicons either in liver tissue or in PBMCs in all patients of the current series. Multiple PCR assays for variable diversity joining (VDJ) IgH gene rearrangements were also performed in the liver compartment. Selective amplification compatible with mono or oligoclonal B cell clonotypes was demonstrated in 80% (6/8) and 25% (2/8) of patients with and without clinical evidence of B-cell disorders. V(H)1 and V(H)3 were the most represented V(H) families. In situ expression of Bcl-2 protein was carried out by immunohistochemistry on liver biopsy sections. Bcl-2 protein was detected in 2 (12.5%) patients who did not associate extrahepatic disorders. In conclusion, current data support the concept that production of IgH gene rearrangements is not associated with Bcl-2/IgH chromosomal translocation in hepatic compartment. Liver overexpression of Bcl-2 protein may occur in at least a minor proportion of HCV-infected patients.
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PMID:HCV-associated B cell clonalities in the liver do not carry the t(14;18) chromosomal translocation. 1662 75

Aim-To investigate whether clinical features of non-Hodgkin's lymphomas, at the time of first biopsy, correlate with studies of cell proliferation and cell death as well as with the level of bcl-2 expression.Methods-Bcl-2 expression, determined by immunocytochemistry, was compared with cell proliferation, measured using in situ hybridisation for histone mRNA, and cell death by apoptosis, measured using in situ end labelling for DNA cleavage.Results-Histone mRNA staining gave a labelling index of 30% of cells for reactive germinal centres, 5.2-13.5% of cells for low grade non-Hodgkin's lymphoma and 12.1-50.5% of cells for high grade non-Hodgkin's lymphoma. In situ end labelling gave a labelling index of 5.0-10.0% of cells for reactive germinal centres, 1.0-3.7% of cells for low grade non-Hodgkin's lymphoma and 4.7-13.5% of cells for high grade non-Hodgkin's lymphoma. There was a positive correlation between apoptotic index and proliferation index. More cases of low grade than high grade non-Hodgkin's lymphoma expressed bcl-2. There was no correlation between apoptotic index and bcl-2 expression for high grade non-Hodgkin's lymphoma.Conclusions-The molecular mechanisms controlling cell proliferation and death in non-Hodgkin's lymphoma are complex, probably involving a range of genes, including bcl-2. A better understanding of resistance to cell death is needed if the clinical goal of tailoring cancer treatment to individual tumours is to be achieved.
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PMID:Correlation between apoptosis, proliferation and bcl-2 expression in malignant non-Hodgkin's lymphoma. 1669 87


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