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 relationship between Epstein Barr Virus (EBV) and the human host is commonly benign, whereas the development of malignancy is most likely due to imbalance between the virus and host's immune system. The aim of this study was to analyze the association of EBV with pediatric lymphomas in human immunodeficiency virus (HIV) patients. Four consecutive patients with a histological and clinical diagnosis of lymphomas among 351 pediatric HIV-infected children prospectively followed up at our hospital since 1991 were studied. The cases included one diffuse fibrosis lymphocyte depletion subtype Hodgkin's lymphoma, 2 Burkitt's lymphomas, and one primary diffuse large B-cell lymphoma of the central nervous system. We assessed EBV presence by LMP-1 protein labeling by immunohistochemistry and in situ hybridization for EBERs in formalin-fixed and paraffin-embedded biopsies from all four cases. All HIV-associated lymphomas studied were found to be associated with EBV. The lymphoproliferative action of EBV may induce oncogenesis by increasing the probability of genetic alterations and/or by expanding an already malignant clone. As an oncogenic protein, LMP-1 expression by tumor cells supports the involvement of EBV in disease pathogenesis.
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PMID:Epstein Barr virus-associated lymphoma in HIV-infected children. 1209 68

Tumorigenesis is a multi-step process involving a series of changes of cellular genes. Most solid tumors and hematopoietic malignancies often show abnormal chromosome numbers, the aneuploidy. The chromosomal aneuploidy keeps cells in the state of chromosomal instability (CIN) that will increase the mutation rate of cells affected and thus push them deeper into the process of tumorigenesis. The yeast genetic studies showed that normal distribution of chromosome during mitosis is under the surveillance of a set of genes, the spindle assembly checkpoint genes, that include the BUB and MAD gene groups and MPS. In some colorectal cancers with CIN it was found to have hBUB1 gene mutated and the mutated gene functions dominantly. We have examined a series of breast cancer cell lines with or without CIN for the hBUB1 gene mutation and found none. However, we detected various degrees of deletion in the coding sequences of the hBUB1 gene in cells from T lymphoblastic leukemia cell lines, Molt3 and Molt4, and cells from some acute lymphoblastic leukemia and Hodgkin's lymphoma patients. So far the lesions of deletion are in the kinetochore localization domain of the hBUB1 gene that may explain why the deletion lesions in the BUB1 gene cause aneuploidy in lymphoma and lymphoma cells. The deletions are heterozygous in nature. Like the mutated hBUB1 gene in colorectal cancer, the mutant hBUB1 cDNA from lymphoblastic leukemia cells behaves dominantly.
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PMID:hBUB1 defects in leukemia and lymphoma cells. 1209 43

The pathogenesis of Kaposi's sarcoma (KS) is better understood since the identification of the novel human herpesvirus 8 (HHV8), which can be found in all forms of KS. Viral oncogenesis and cytokine-induced growth, as well as some states of immunocompromise, contribute to its development. Several virally encoded genes--eg, bcl-2, interleukin 6, cyclin D, G-protein-coupled receptor, and interferon regulatory factor--provide key functions on cellular proliferation and survival. Growth promotion of KS is further stimulated by various proinflammatory cytokines and growth factors such as tumour necrosis factor a, interleukin 6, basic fibroblast growth factor, and vascular endothelial growth factor, resulting in a hyperplastic polyclonal lesion with predominant spindle cells derived from lymphoid endothelia. HHV8 has recently been discovered to escape HLA-class-I-restricted antigen presentation to cytotoxic T lymphocytes by increasing endocytosis of MHC class I chains from the cell surface, thus enabling latent infection and immune escape in primary and chronic infection. Multicentric Castleman's disease is a rare lymphoproliferative disorder of the plasma cell type, which has been reported in both HIV-seropositive and HIV-seronegative patients, and which frequently contains HHV8 DNA. Pleural effusion lymphoma, or body-cavity-based lymphoma, belongs to the group of non-Hodgkin B-cell lymphomas characterised by pleural, pericardial, or peritoneal lymphomatous effusions in the absence of a solid tumour mass. Pleural effusion lymphoma has an intermediate immunophenotype lacking B or T lymphocyte antigens and also belongs to the diseases associated with HHV8.
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PMID:Update on Kaposi's sarcoma and other HHV8 associated diseases. Part 2: pathogenesis, Castleman's disease, and pleural effusion lymphoma. 1214 97

AP-1 family transcription factors have been implicated in the control of proliferation, apoptosis and malignant transformation. However, their role in oncogenesis is unclear and no recurrent alterations of AP-1 activities have been described in human cancers. Here, we show that constitutively activated AP-1 with robust c-Jun and JunB overexpression is found in all tumor cells of patients with classical Hodgkin's disease. A similar AP-1 activation is present in anaplastic large cell lymphoma (ALCL), but is absent in other lymphoma types. Whereas c-Jun is up-regulated by an autoregulatory process, JunB is under control of NF-kappa B. Activated AP-1 supports proliferation of Hodgkin cells, while it suppresses apoptosis of ALCL cells. Furthermore, AP-1 cooperates with NF-kappa B and stimulates expression of the cell-cycle regulator cyclin D2, proto-oncogene c-met and the lymphocyte homing receptor CCR7, which are all strongly expressed in primary HRS cells. Together, these data suggest an important role of AP-1 in lymphoma pathogenesis.
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PMID:Aberrantly expressed c-Jun and JunB are a hallmark of Hodgkin lymphoma cells, stimulate proliferation and synergize with NF-kappa B. 1214 10

Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin lymphoma. In contrast to many other hematological malignancies, no chromosomal abnormalities with a diagnostic or prognostic value have been identified in DLBCL. Numerical chromosomal imbalances were characterized by comparative genomic hybridization (CGH) performed on 54 DLBCL tumors from a total of 40 patients. The clonal relatedness was demonstrated in 9 of 11 pairs of matched diagnostic tumors and their relapses as determined by IGH gene rearrangement analysis and/or the CGH profiles. Furthermore, immunohistochemical expression analyses of BCL2 and BCL6/LAZ3 were performed on all cases. Copy number changes were detected in 94% of the diagnostic tumor samples and in all of the relapses. Chromosomal losses in diagnostic tumors were preferentially observed at 8p22-pter (29%), 1p34-pter (26%), 6q23-qter (20%), 17p12-pter (17%) and 22q (17%), 9p23-pter (14%), whereas gains were mainly seen in Xq25-26 (43%), 13q22 (26%), 12cen-q14 (20%), 3q24-25 (11%), 7 (11%), and 18q12-21 (11%). Loss of 22q was significantly more commonly seen in the diagnostic tumor samples with more advanced clinical stage in other words, Stage III-IV compared with Stage I-II, and band 18q21 was significantly more often gained in relapses as compared to diagnostic tumors. None of the recurrent alterations were detected as a single abnormality, suggesting that other genetic lesions below the detection level of CGH may be the initiating event in the tumorigenesis of DLBCL. However, the distribution of CGH alterations support the idea of a progression of genetic events where loss of 8p and 9p and gain of 3q, 13q, and 18q would represent relatively early events because they were distributed in tumors with only two abnormalities.
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PMID:Chromosomal imbalances in diffuse large B-cell lymphoma detected by comparative genomic hybridization. 1218 Dec 65

B-cell malignancies account for the majority of lymphoid tissue neoplasia. Similar to normal B cells, malignant B cells in most Hodgkin's and non-Hodgkin's types of lymphomas express B-cell receptor (BCR) on their membrane. Since neoplastic B cells retain the capacity to respond to microenvironmental signals, and in many respects still behave as normal B cells, it does not seem bizarre that the BCR, which dominates the biology of normal B cells, can remain equally important for some malignant B cells. Indirect evidence suggests that retained BCR expression, and in certain cases coupled with stimulation by antigen (Ag), may be necessary for the viability of some B-cell tumors. The aim of this review is to consider the evidence regarding the role of the BCR in tumorigenesis of B-cell lymphomas, and discuss different approaches used in evaluating this role in the persistence and progression of these malignancies. The diversity in B-cell lymphomas prevents easy classification of these cancers based on their dependence on BCR expression. It seems likely that some malignant B cells need BCR expression, or additionally, stimulation by Ag in order to survive. However, through accumulation of additional genetic changes, the original tumor can give rise to a clone that no longer requires signals from the BCR to survive. Thus, most B-cell lymphomas may initially retain dependence on BCR expression that governs normal B-cell physiology and may lose it only at later stages of tumor progression, through the accumulation of additional transforming events.
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PMID:Malignant B cells and antigenic receptor: necessity or habit? 1238 17

The activation of the NF-kappaB family of transcription factors plays a crucial role in oncogenesis. The IkappaB family has the ability to retain the NF-kappaB in an inactive complex in the cytoplasm. Recently, mutations of the IkappaBalpha gene were found in Hodgkin's lymphoma, which allows NF-kappaB proteins to translocate into the nucleus in an active form. In this report, we describe a mutational analysis of IkappaBalpha for primary tumor cells obtained from patients with a variety of hematologic malignancies (acute myelogenous leukemia, chronic myelogenous leukemia, myelodysplastic syndrome, hairy cell leukemia, adult T-cell leukemia, and mantle cell lymphoma) as well as 15 leukemia, lymphoma, and myeloma cell lines (HL60, U937, HEL, K562, NALM1, Jurkat, JM, MOLT4, Raji, KS1, OKM2T, OKM3T, F6T, Su9T01, and C2-2). RT-PCR, followed by direct sequencing, was performed and all samples expressed IkappaBalpha. One missense mutation was identified in a primary effusion lymphoma cell line, KS1. However, NF-kappaB (p65) protein was absent from the nucleus of KS1 immunohistochemically, suggesting that the mutation did not alter the function of IkappaBalpha in this case. Taken together, although it is not clear whether normal IkappaBalpha protein was expressed in hematologic malignancies, mutations of IkappaBalpha could be rare events in these diseases, except for Hodgkin's lymphoma. Alterations of other members of NF-kappaB/ IkappaB family proteins might act on the development of hematologic malignancies.
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PMID:Mutational analysis of IkappaBalpha in hematologic malignancies. 1252 85

Chromosomal translocations involving t(14;18)(q32;q21) and the chromosome 3q27 region are common in B-cell non-Hodgkin lymphoma of germinal center cell origin. Grade 3B follicular lymphoma (FL), consisting almost exclusively of centroblasts, is a distinct subgroup of follicular lymphomas that has more in common clinically with the aggressive diffuse large B-cell lymphomas than with their indolent FL grade 1 and 2 counterparts. We studied the cytogenetic and molecular genetic aberrations by classic cytogenetics, polymerase chain reaction, Southern blot hybridization, and fluorescence in situ hybridization, with special emphasis on t(14;18), affecting bcl-2, and 3q27 rearrangement, affecting bcl-6, in 32 cases of FL grade 3B. Three distinctive subgroups were identified based upon the existence of breakpoint 3q27, a translocation t(14;18), or the absence of both. Group I involved a t(14;18) and no 3q27 aberrations (n = 13); group II was without a t(14;18) and without 3q27 aberrations (n = 9), but had other cytogenetic aberrations; and group III was without a t(14;18) but with aberrations involving 3q27 (n = 10). None of the FL grade 3B cases harbored both a t(14;18) and 3q27 aberration. These results, in particular the finding of a mutual exclusiveness of bcl-2 and bcl-6 rearrangement, indicate at least 3 different pathways of oncogenesis in FL grade 3B. FL grade 3B with bcl-2 rearrangement probably is part of the same entity as the other follicular lymphomas (1, 2, 3A), whereas the cases with 3q27 abnormalities or other unrelated translocations are more closely related to the majority of diffuse large-cell lymphomas of germinal center cell origin.
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PMID:Follicular lymphoma grade 3B includes 3 cytogenetically defined subgroups with primary t(14;18), 3q27, or other translocations: t(14;18) and 3q27 are mutually exclusive. 1252 93

The present status of the following aspects of diagnosis and treatment of malignant lymphoma are reviewed, and future directions are discussed. 1. Epidemiology 2. Pathological classification 3. Molecular analysis of oncogenesis and disease progression 4. Staging classification and response evaluation 5. State-of-the art therapy of major subtypes 1) Hodgkin's lymphoma 2) Aggressive non-Hodgkin's lymphoma 3) Indolent B-cell non-Hodgkin's lymphoma 4) Salvage therapy for relapsed cases 6. New agent development focusing on antibody therapy 1) Principles and history of antibody therapy 2) Clinical development of rituximab in the USA and Japan 3) Radioimmunotherapy Recently, the importance of evidence-based medicine has been widely recognized not only by physicians but also by patients themselves. To further improve the therapeutic results, it is extremely important to conduct well-designed clinical trial consecutively.
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PMID:[New trends in the diagnosis and treatment of malignant lymphoma]. 1269 61

Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus associated with the development of both lymphoid and epithelial tumours. As a common virus infection, EBV appears to have evolved to exploit the process of B cell development to persist as a life-long asymptomatic infection. However, the virus can contribute to oncogenesis as evidenced by its frequent detection in certain tumours, namely Burkitt's lymphoma (BL), post-transplant B cell lymphomas, Hodgkin's disease (HD) and nasopharyngeal carcinoma (NPC), and by its unique ability to efficiently transform resting B cells in vitro into permanently growing lymphoblastoid cell lines (LCLs). These transforming effects are associated with the restricted expression of EBV genes such that only a subset of so-called latent virus proteins are expressed in virus infected tumours and in LCLs. Distinct forms of EBV latency are manifest in the different tumours and these appear to be a vestige of the pattern of latent gene expression used by the virus during the establishment of persistent infection within the B cell pool. This review summarises our current knowledge of EBV latent gene function and how this relates to the role of the virus in the aetiology of different tumours.
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PMID:Epstein-Barr virus and oncogenesis: from latent genes to tumours. 1291 Feb 48


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