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)

Low-grade non-Hodgkin's lymphomas are characterized by a low proliferative activity and prolonged clinical course. Most of them reveal distinct cytogenetic and molecular aberrations, such as the translocation t (14; 18) in centrocytic/centroblastic or follicular lymphomas, which is combined with an overexpression of the bcl 2 oncogene or the translocation t (11; 14), which is associated with a deregulation of the PRAD 1 gene and is mainly found in centrocytic or mantle-cell lymphomas. The therapy of low-grade non-Hodgkin's lymphoma depends on the extent of the disease. In early stages I and II, in which only 15 to 25% of low-grade lymphomas are diagnosed, radiotherapy represents the treatment of choice and may be applied with curative intention. The appropriate treatment of more advanced stages III and IV is a matter of controversial debates. Currently, it still seems justified to watch the natural course of the disease and to start therapy not before the occurrence of B-symptoms, hematopoietic insufficiency or progression of lymphoma. Intensification of initial cytoreductive chemotherapy does not result in a prolonged survival or a higher remission rate. However, maintenance therapy with interferon alpha following successful initial cytoreductive chemotherapy appears to have a favorable impact on disease-free and possibly also overall survival. New perspectives result from the introduction of new cytostatic compounds and the purine analogues in particular as well as the development of effective immunotoxins and antibody-conjugated radio-isotoes. Furthermore, myeloablative radiochemotherapy followed by autologous bone marrow or peripheral stem cell transplantation provides a promising approach with curative potential even in advanced stages of the disease.
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PMID:[Therapy of low-grade non-Hodgkin lymphomas]. 864 98

Non-Hodgkin's lymphomas (NHL) are a heterogeneous group of disorders which can either be classified according to their biology, represented by corresponding counterparts of normal lymphocyte development as in the Kiel classification, or according to their clinical course, used in the Working Formulation. The recently proposed Revised European-American Lymphoma (R.E.A.L.) classification may unify both aspects and facilitate the comparability of international studies. Besides histology, the extent of disease still comprises the major determinant of therapy. In high-grade lymphomas combination chemotherapy with cyclophosphamide, hydroxydaunorubin, vincristine and prednisone (CHOP) represents the treatment of first choice, and may be restricted to 3-4 cycles in patients with limited stages of the disease when followed by involved field radiotherapy. In more extended, bulky stage II to IV disease, treatment must be extended to six courses of CHOP and, potentially, additional irradiation. Even in advanced states of the disease, long-term remission and potential cure are achieved in 30-50% of cases. In low-grade lymphomas, most patients present with advanced stages III and IV for which chemotherapy can be applied with palliative intention only. Hence, a watch-and-wait approach still seems appropriate outside clinical investigations until the disease requires a therapeutic intervention. This consists preferentially of chemotherapy of moderate intensity such as cyclophosphamide, vincristine and prednisone (COP) or prednimustine and mitoxantrone (PmM). In responding patients, maintenance therapy with interferon-alpha is currently being explored and may result in prolongation of disease-free and, possibly also, overall survival. In both high- and low-grade lymphomas, intensification of therapy by myeloablative chemotherapy or combined chemoradiotherapy followed by autologous bone marrow transplantation (ABMT) or peripheral stem cell transplantation provides a promising and potentially curative prospective. In addition, new cytostatic agents such as the purine analogues--fludarabine, chlorodeoxyadenosine and deoxycoformycin--enlarge the therapeutic spectrum. More experimental approaches consist of the application of immunotoxins or radioisotypes, coupled to monoclonal antibodies directed against lymphoma-specific antigens. Overall, the substantial advances that have been achieved in the understanding of the biology and pathogenesis of malignant lymphomas, as well as the current achievements of therapy and the new promising perspectives, justify the hope that curative therapy can soon be offered to an increasing proportion of patients with NHL.
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PMID:Non-Hodgkin's lymphomas--current status of therapy and future perspectives. 865 30

Mantle cell lymphoma (formerly known as intermediate lymphocytic lymphoma, diffuse centrocytic lymphoma, or diffuse small cleaved lymphoma) is one of the small cell non-Hodgkin lymphoma entities that is clinically more aggressive than small lymphocytic lymphoma, and needs to be separated from it. Mantle cell lymphoma is strongly associated with the t(11;14) chromosomal translocation that rearranges the bcl-1 oncogene (PRAD-1 gene) and immunoglobulin heavy chain gene. In this study, we developed a nested polymerase chain reaction system to evaluate the t(11;14) translocation. The study material consisted of 10 mantle cell lymphomas fulfilling the criteria suggested by other authors (P. M. Banks et al. Surg Pathol 16:637, 1992). A novel nested polymerase chain reaction system was used to evaluate the bcl-1 breaks in the major translocation cluster using two successive polymerase chain reaction amplifications. This reaction yielded a background-free single product of the size of 200 to 300 base pairs in four of 10 mantle cell lymphomas. The identity of the product from the nested polymerase chain reaction was confirmed by Southern blotting followed by hybridization with a specific probe. The amplification products were also evaluated by Sst-I, Alu-I, Dde-I, and Ita-I restriction enzymes and showed different patterns of digestion reflecting individual differences between the MTC/ IgH junctions. A selection of other low-grade lymphomas, including lymphocytic, follicular, and mucosa-associated lymphoid tissue lymphoma, and hairy cell leukemia and 29 hyperplastic lymph nodes were negative. This nested polymerase chain reaction system for the t(11;14) translocation involving major translocation cluster offers a convenient specific identification for mantle cell lymphoma. However, this test has a limited diagnostic power because only about half of the mantle cell lymphomas show the bcl-1 breaks in the major translocation cluster. The test performs well in formaldehyde-fixed and paraffin-embedded material, allowing the study of large numbers of retrospective cases of mantle cell lymphomas.
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PMID:Molecular diagnosis of mantle cell lymphoma in paraffin-embedded tissue. 872 72

Malignancies in children with HIV infection have not been as frequent as expected, but they still constitute a fertile area for clinical and basic research. Non-Hodgkin's lymphomas are the most frequent malignancies of children with AIDS and are curable diseases with standard chemotherapy. Leiomyomas and leiomyosarcomas have become the second leading cancer of children with HIV infection and are clearly associated with EBV infection. Treatment for these lesions has not been as successful as that for lymphomas. Other infrequent atypical lymphoproliferative lesions of these patients can often be categorized in the MALT group. Some of these are low-grade lymphomas, whereas others can progress to high grade. The diagnosis of Kaposi's sarcoma in children with AIDS should be carefully reviewed by pathologists experienced with these cases. The diagnosis of KS in children must be made with special care, because some other lesions of HIV-infected children (such as prominent vascularity in lymph nodes) can be confused with KS. Other tumors of these patients are rare and probably are no more frequent than would be expected in the normal population. Because malignancies in children with AIDS are rare, it is important that each one be studied completely with regard to type and incidence, risk factors, and biologic features. To this end, the Pediatric Oncology Group (POG) has established a national registry and treatment protocols. Patient information as well as fresh, frozen, and fixed specimen studies are coordinated through the POG Statistical Office in Gainesville, Florida (telephone, 904-392-5198; FAX, 904-392-8162). The collaborative efforts of all physicians treating children with AIDS and malignancies will be needed to advance our knowledge and efficacy in treating these diseases.
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PMID:Cancers in children with HIV infection. 888 Feb 5

Morphologic, immunohistochemical and immunogenetic studies were performed on 28 cases of primary gastric lymphoma from fresh frozen tissue. Eight cases were diagnosed as diffuse large B-cell lymphoma, four as follicular center lymphoma (follicular), five as mucosa-associated lymphoid tissue (MALT) lymphoma, three as plasmacytoma, and three as T-cell lymphoma, two as mantle cell lymphoma, one as follicular center lymphoma (diffuse, predominantly small cell), and one as lymphoplasmacytoid lymphoma, and one as Hodgkin's disease. From immunohistochemical studies, four types of morphologically similar low-grade lymphomas can be differentiated by a combination of various monoclonal antibodies. Cases of diffuse large B-cell lymphoma may have a germinal center origin. We observed lympho-epithelial lesions in cases of non-MALT lymphomas. We therefore consider that the current diagnostic criterion for MALT lymphoma may not always be valid. Except for cases of T-cell lymphoma and Hodgkin's disease, 17 out of 22 cases revealed clonal rearrangement bands of the JH gene. In situ hybridization (ISH) and polymerase chain reaction (PCR) studies revealed the presence of Epstein-Barr (EB) virus genomes in two and three cases, respectively. Epstein-Barr virus may play a role in lymphomagenesis, although on relatively rare occasions.
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PMID:Primary gastric lymphomas: morphologic, immunohistochemical and immunogenetic analyses. 890 70

The nm23-H1 gene is a putative metastasis-suppressor gene encoding a 17 kDa protein with nucleoside diphosphate kinase activity. Expression of nm23-H1/NDPK-A correlates inversely with the metastasising potential of some human tumours and experimental animal cells. No nm23 expression studies exist for human malignant lymphomas so far. In this study, we examined nm23-H1 expression by Northern and immunohistochemical analysis in 106 primary lymphoma samples from patients with Hodgkin's disease (HD) (n = 15), high-grade non-Hodgkin's lymphoma (NHL) from different lineages (n = 71) and low-grade NHL (n = 20). Both inter- and intra-subtype variations in nm23-H1/NDPK-A expression levels were demonstrated by all disease subtypes. Besides this heterogeneity, a general trend towards highly malignant samples expressing higher nm23-H1/NDPK-A, levels than the low-grade lymphomas was observed. Both adult and childhood HD and high-grade NHL samples exhibited significantly higher NDPK-A expression than the low-grade NHL found only in adults. High nm23-H1/NDPK-A levels in lymphoma samples did not always reflect proliferative activity of tumour cells as monitored by Ki-67 antigen staining. Fifty samples were further investigated for possible mutations in the nm23-H1 coding sequence by means of reverse transcriptase-polymerase chain reaction (RT-PCR) and single-strand conformation polymorphism (SSCP) analysis. No mutation was found by this screening. Our results suggest a role for nm23-H1 expression in the disease aggressiveness of lymphomas.
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PMID:Variability of nm23-H1/NDPK-A expression in human lymphomas and its relation to tumour aggressiveness. 895 79

A discordance between p53 protein overexpression and the presence of mutations in the gene has been observed in many types of tumors, including human lymphomas. To probe this finding, we have studied a large series of 94 lymphomas of different pathologic types and histologic differentiation. Analyzing exons 5-9, we have found mutations in the p53 gene in 7 of 94 cases distributed in different subtypes: 4/12 (33%) high-grade B-cell non-Hodgkin's lymphomas (B-NHLs), in 1 of 5 (20%) high-grade mucosa-associated lymphomas (MALT), in 1 of 22 (4.5%) anaplastic large cell lymphoma (ALCL), and in 1 of 24 (4%) T-cell NHLs. Immunostaining with anti-p53 antibody DO-7 was possible in 87 lymphomas, and overexpression of p53 protein was observed in 16 cases (18%). A discrepancy between the results of SSCP and immunostaining was detected on 18 tumor samples. Two cases with mutations in the gene showed no altered protein expression and 16 cases overexpressed p53 protein had no point mutations. In these cases, the possibility that mutations occur outside the exons studied has been tested and the entire coding sequence analyzed. Only one case showed a mutation in exon 10, and we found two cases carrying a polymorphism in exon 4 and in intron 10. We conclude that mutations in p53 occur mainly in high-grade B-cell NHLs. Although not limited to a specific subtype of lymphoma, they may be rare in Hodgkin's disease and in low-grade lymphomas. The discrepancies between overexpression and presence of mutations suggest (1) the existence of another mechanism to stabilize the p53 protein, and (2) that the immunohistochemistry cannot be used to predict mutations in the gene.
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PMID:Correlation between mutations in p53 gene and protein expression in human lymphomas. 913 10

Inhibitors of programmed cell death (apoptosis) aberrantly prolonging cell viability may contribute to cancer by facilitating the insurgence of mutations and by promoting resistance to therapy. Despite the identification of several new apoptosis inhibitors related to bcl-2 or to the baculovirus IAP gene, it is not clear whether apoptosis inhibition plays a general role in neoplasia. Here, we describe a new human gene encoding a structurally unique IAP apoptosis inhibitor, designated survivin. Survivin contains a single baculovirus IAP repeat and lacks a carboxyl-terminal RING finger. Present during fetal development, survivin is undetectable in terminally differentiated adult tissues. However, survivin becomes prominently expressed in transformed cell lines and in all the most common human cancers of lung, colon, pancreas, prostate and breast, in vivo. Survivin is also found in approximately 50% of high-grade non-Hodgkin's lymphomas (centroblastic, immunoblastic), but not in low-grade lymphomas (lymphocytic). Recombinant expression of survivin counteracts apoptosis of B lymphocyte precursors deprived of interleukin 3 (IL-3). These findings suggest that apoptosis inhibition may be a general feature of neoplasia and identify survivin as a potential new target for apoptosis-based therapy in cancer and lymphoma.
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PMID:A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. 925 86

Non-Hodgkin's lymphomas (NHLs) in man are on the increase. They are also common in dogs, which, as close companions of man, may constitute a useful experimental model. However, comparisons cannot be made without a reliable morphological and immunological classification of canine NHL. Canine NHLs (n = 134) were classified on the basis of fine-needle lymph-node aspirates according to the Kiel classification, and 92 were re-classified according to the Working Formulation and the updated Kiel classification, in a histological and immunological study. The immunophenotype was determined (1) in 92 cases by the use of the pan-T anti-CD3 polyclonal antibody and the pan-B anti-mb1 monoclonal antibody on paraffin wax-embedded tissue sections, and (2) in 47 cases by the use of a panel of polyclonal and monoclonal antibodies on fresh preparations and frozen tissue. Cytological analysis showed a predominance of high-grade lymphomas (73.9%) over low-grade lymphomas (26.1%); it also demonstrated forms not reported in other species (small-cell variants, lymphomas with macronucleolated medium-sized cells [MMCs], and polymorphic lymphomas with a centroblastic component). Histological examination revealed the rarity of follicular lymphomas (2.2% of cases), an appearance suggestive of T-cell neoplasia (8.7% of cases), and evidence that some MMC lymphomas originated in the marginal perifollicular zones. Some (26%) of the lymphomas were of the T-cell phenotype: the majority of these consisted of small-cell, low-grade lymphomas and mycosis fungoides, the rest being either high-grade pleomorphic lymphomas (mixed or large-cell) or, rarely, high-grade, small noncleaved-cell, plasmacytoid lymphomas. No lymphoma expressed a double (T and B) phenotype. This study revealed similarities with, but also notable differences from, human NHL. In particular, the MMC lymphomas may constitute an interesting equivalent of human marginal zone B-cell lymphomas.
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PMID:Cytohistological and immunological classification of canine malignant lymphomas: comparison with human non-Hodgkin's lymphomas. 926 43

The cell cycle regulatory protein cyclin D1 is essential for G1-S phase transition in several epithelial and mesenchymal tissues but is apparently not essential in normal mature B cells. An overexpression of cyclin D1 is induced by the chromosomal translocation t(11;14)(q13;q32), which characterizes non-Hodgkin's lymphomas (NHLs) of mantle cell type. We studied 26 cases of mantle cell lymphoma (MCL) for the expression of cyclins D1 and D3. A total of 23 lymphomas showed a nuclear staining for cyclin D1, whereas reactive B cells of residual germinal centers were constantly negative. When compared with cyclin D3, an inverse staining pattern emerged. Whereas the B cells of residual germinal centers reacted strongly positive for cyclin D3, there was low or missing expression of cyclin D3 in MCL cells. In other B-cell lymphomas (n = 55), including chronic lymphocytic leukemia, low-grade lymphomas of mucosa-associated lymphatic tissue, follicular lymphomas, and diffuse large B-cell lymphomas, no cyclin D1 expression could be detected and 89% of these cases displayed cyclin D3 positivity. Lymphoma cell lines harboring the t(11;14) showed cyclin D1 protein but no or very low levels of cyclin D3; three other B-cell lines, a T-cell line, and peripheral blood lymphocytes strongly expressed cyclin D3 and reacted negatively for cyclin D1. We conclude that the chromosomal translocation t(11;14) leads to an abnormal protein expression of cyclin D1 in the tumor cells of MCL and induces a consecutive downregulation of cyclin D3. In contrast to other B-NHLs, cyclin D1 and D3 expression in MCL is not related to the growth fraction.
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PMID:Cyclin D1 expression in mantle cell lymphoma is accompanied by downregulation of cyclin D3 and is not related to the proliferative activity. 937 97


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