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)

Mantle cell lymphoma (MCL) is a unique subtype of B-cell non-Hodgkin lymphomas characterized by the chromosomal translocation t(11;14)(q13;q32) and nuclear cyclin D1 overexpression in the vast majority of cases. Most patients present with advanced stage disease, often with extranodal dissemination, and pursue an aggressive clinical course in the majority of cases. Recent improvement has been achieved by the successful introduction of monoclonal antibodies and dose-intensified approaches including autologous stem cell transplantation (ASCT) strategies. With the exception of allogeneic hematopoietic stem cell transplantation, current treatment approaches are non-curative and the corresponding survival curves are characterized by a delayed, but continuous decline and a median survival of 4 to 6 years. However, recently a subset (15%) of long-term survivors have been identified with a rather indolent clinical course even after conventional treatment strategies only. Emerging strategies such as proteasome inhibitors, IMIDs, mTOR inhibitors and others are based on the dysregulated control of cell cycle machinery and impaired apoptotic pathways. Monotherapy of these compounds achieves efficacy comparable to conventional chemotherapy in relapsed MCL, and combination strategies are currently being investigated in numerous trials; however, their introduction into clinical practice and current treatment algorithms remains a challenge.
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PMID:Current treatment standards and emerging strategies in mantle cell lymphoma. 2000 39

Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin lymphoma characterized by cyclin D1 overexpression as a result of the t(11;14) chromosomal translocation, and by biological and clinical heterogeneity with frequent extranodal dissemination. There is no consensus or standard for initial therapy or for treatment of relapsed disease, and no proven curative therapy exists. Nonetheless, considerable progress in treatment response and survival has been realized over the past several years, and the disease remains an important focus of preclinical and clinical research. Advances in the biologic understanding of MCL, new molecular targets and therapeutic strategies, and the applications of biomarkers for risk stratification and molecular targeting were reviewed at a recent MCL Workshop. These are summarized herein, and are intended as both a status report on areas of active investigation and to serve as a template for future research.
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PMID:Mantle cell lymphoma: report of the 2009 Mantle Cell Lymphoma Consortium Workshop. 2003 19

In mouse models and cell lines, murine double minute 2 (MDM2) and MDM4 have been shown to synergistically promote proteasome-mediated degradation of p21 and p53. MDM4 also inhibits p53-mediated transcriptional activation of p21. p53 expression results in increased p21 expression, a negative cell-cycle regulatory protein and an inhibitor of cyclin D1. As mantle cell lymphoma is characterized by cyclin D1 overexpression, we assessed for human homolog of MDM4 (HDM4) expression and its effect on p21 in mantle cell lymphoma. Using immunohistochemical methods, in reactive lymph nodes (n=19) germinal center cells strongly expressed HDM4 in the nucleus and the cytoplasm, but mantle zone B-cells were only dimly positive. In mantle cell lymphoma tumors, aberrant HDM4 nuclear expression was observed in 18 of 19 (95%) cases. In contrast, HDM4 in other B-cell non-Hodgkin lymphoma types retained its normal pattern of expression. To further characterize the differential upregulation of HDM4 in mantle cell lymphoma, HDM4 was assessed by quantitative real-time polymerase chain reaction in four mantle cell lymphoma cell lines (Granta 519, Z-138, SP-53, and Mino) and six mantle cell lymphoma tumors. Both the splicing variant HDM4-S, containing only the p53-binding domain, and full length HDM4 were increased compared with normal CD19+ B-cells (P<0.05). Using small interfering RNA to inhibit HDM4 in the SP53 and Mino cell lines showed increased p21 and active caspase-3, the latter indicating increased apoptosis. Our results show that HDM4 is overexpressed in mantle cell lymphoma and, at least in part, exerts its effect by suppressing p21 expression, thereby enhancing cell-cycle progression. Inhibition of HDM4 may serve as a potential approach in the design of therapy for patients with mantle cell lymphoma.
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PMID:HDM4 is overexpressed in mantle cell lymphoma and its inhibition induces p21 expression and apoptosis. 2006 13

We present the case of a 65 years old male, admitted in the Hematology Department of the Universitary Emergency Hospital Bucharest, complaining of physical asthenia and weight loss; periodical medical examination has revealed splenomegaly and leucocytosis with lymphocytosis, persistent for the past 3 years. The clinical and paraclinical exam demonstrated splenomegaly (21 cm in diameter on computer tomography scan), hepatomegaly and generalized lymphadenopathies. The laboratory tests confirmed leucocytosis with lymphocytosis--a clonal population of B lymphocytes CD20+ CD19+ CD23+/- CD79b+(low), CD43+ FMC7+ CD5+ CD38+ ZAP70+ cyclin D1-. Lymph node and bone marrow biopsy together with flowcytometry established the diagnosis of Malignant non-Hodgkin Lymphoma--Atypical Splenic Marginal Zone B-cell lymphoma (aberrant expression of CD5) stage IVB, with leukemic picture, complicated with autoimmune hemolytic anemia with highly positive Coombs' tests. We performed therapeutic splenectomy, which was difficult because of the dimensions of the organ. The short term evolution was complicated by acute complete thrombosis of the splenic vein, but the long term evolution (1 year follow-up) was favorable--remission of anemia, significant improvement of performance status, decrease of leucocytosis and reduction of the tumoral mass.
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PMID:Splenectomy--a therapeutic option in splenic marginal zone cell lymphoma. 2006 70

Primary gastrointestinal involvement of mantle cell lymphoma (MCL) is rare with a frequency reported between 4 and 9% of all gastrointestinal B-cell non-Hodgkin lymphomas. It was first described and so-called as multiple lymphomatous polyposis (MLP). Its clinical presentation is usually characteristic, with multiple lymphomatous polyps involving several digestive tract segments and a marked tendency towards extra-intestinal spread. The constant and typical phenotypic features of the small cleaved tumour cells, characterised as CD20+, CD5+ CD23- with a t(11;14) (q13;q32) and cyclin D1 overexpression on immunochemistry, allow MLP to be considered as the gastrointestinal counterpart of peripheral nodal MCL. They both share a very poor outcome. Response to intensive chemotherapy regimens usually results in regression of macroscopic and sometimes microscopic lesions but remissions are short and median survival from 3 to 4 years. Prognosis has been significantly improved since in younger patients, intensive front-line immunochemotherapy with autologous stem cell transplantation has been proposed. Earlier diagnosis with further studies integrating novel agents are still required to determine the optimal treatment with less toxicity.
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PMID:Primary gastrointestinal tract mantle cell lymphoma as multiple lymphomatous polyposis. 2020 7

Mantle cell lymphoma (MCL) is a rare non-Hodgkin lymphoma (NHL) entity. The translocation between chromosomes 11 and 14 is the cytogenetics hallmark of MCL. This translocation leads to the dysregulation of the CCDN1 gene, and overexpression of cyclin D1 which promotes cell cycling. Despite a classical phenotype (CD19+, CD20+, CD5+, CCND1+, CD10-, CD23-, Bcl-2+, Ig at the membrane, mainly IgM), MCL is not a homogeneous disease and several cytological, phenotypic, cytogenetic and clinical variants have been described. MCL represents 5 % of NHLs with its incidence constantly increasing over the last years. Median age at diagnosis is 68 years. Stage III-IV disease is observed in more than 80 % of patients at presentation, with intestinal and bone marrow being the most frequently involved organs, while the spleen is enlarged in half of cases. Intensive strategies including high-dose chemotherapy, followed by autologous stem cell transplantation have significantly improved the outcome of MCL patients. Median overall survival rate increased from 3 to 5 years during the last decade. At present, induction chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation is the standard regimen in younger patients. However, most of MCL patients will experience relapse. Thus, close monitoring of minimal residual disease (currently under evaluation) may represent a valuable tool for assessment of disease response during follow-up. Future innovative therapies that are being presently investigated in prospective trials include transduction pathways inhibitors, proteasome inhibitors, pro-apoptotic molecules, immunotherapy and/or radiolabeled immunotherapy, and will likely open a new era for targeted therapies in MCL.
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PMID:[Mantle cell lymphoma: an overview from diagnosis to future therapies]. 2048 92

Mantle cell lymphoma (MCL) is a rare subtype of non-Hodgkin lymphoma characterized by CD5 expression and a t(11;14) cytogenetic translocation that results in overexpression of the cyclin D1 gene. Currently, there is no standard of care for the treatment of MCL, and patient prognosis is poor. Traditional treatments for MCL rely on conventional chemotherapy agents, including cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). The addition of the immunotherapeutic agent rituximab to this regimen (CHOP-R) has helped to improve patient response to treatment. These treatments often provide good initial responses that are difficult to sustain. Therefore, a number of newer agents and combinations have been investigated to produce more durable benefit. Several of these advances were reported at the 51st American Society of Hematology (ASH) Annual Meeting and Exposition, held December 5-8, 2009 in New Orleans, Louisiana. In this clinical roundtable monograph, new strategies in the treatment of MCL are discussed. Some of the drug classes examined here are proteasome inhibitors, inhibitors of the protein mammalian target of rapamycin (mTOR), the unique alkylating agent bendamustine, and immunomodulatory agents.
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PMID:Clinical roundtable monograph: Recent advances in the treatment of mantle cell lymphoma: a post-ASH 2009 discussion. 2053 72

Mantle cell lymphoma (MCL) is a rare subtype of non-Hodgkin lymphoma characterized by CD5 expression and a t(11;14) cytogenetic translocation that results in overexpression of the cyclin D1 gene. Currently, there is no standard of care for the treatment of MCL, and patient prognosis is poor. Traditional treatments for MCLrely on conventional chemotherapy agents, including cyclophosphamide, doxorubicin, vincristine, and prednisone(CHOP). The addition of the immunotherapeutic agent rituximab to this regimen (CHOP-R) has helped to improve patient response to treatment. These treatments often provide good initial responses that are difficult to sustain. Therefore, a number of newer agents and combinations have been investigated to produce more durable benefit. Several of these advances were reported at the 51st American Society of Hematology (ASH)Annual Meeting and Exposition, held December 5-8, 2009 in New Orleans, Louisiana. In this clinical roundtable monograph, new strategies in the treatment of MCL are discussed. Some of the drug classes examined here are proteasome inhibitors, inhibitors of the protein mammalian target of rapamycin (mTOR), the unique alkylating agent bendamustine, and immunomodulatory agents.
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PMID:Recent advances in the treatment of mantle cell lymphoma: a post-ASH 2009 discussion. 2055 50

Mantle cell lymphoma (MCL) is an aggressive histotype of B-cell non-Hodgkin lymphoma that has increased in incidence over the past few decades and is incurable, usually poorly responsive to standard chemotherapy combinations, and associated with poor prognoses. Discovering new therapeutic agents with low toxicity that produce better outcomes in patients with MCL is an ongoing challenge. Recent studies showed that degrasyn, a novel small-molecule inhibitor of the Janus kinase/signal transducer and activation of transcription (JAK/STAT) pathway, exerts antitumor activity in lymphoid tumors by inhibiting key growth and survival signaling (JAK/STAT) pathways. In the present study, we found that treatment of both typical and blastoid-variant MCL cells with degrasyn in combination with bortezomib resulted in synergistic growth inhibition and apoptosis induction in vitro. The apoptosis in these cells was correlated with the downregulation of constitutive NF-kappaB and phosphorylated STAT3 activation, leading to the inhibition of c-Myc, cyclin D1, and bcl-2 protein expression and the upregulation of bax protein expression. In vivo, degrasyn and bortezomib interacted to synergistically prevent tumor development and prolong survival durations in a xenotransplant severe combined immunodeficient mouse model of MCL. These findings suggest that agents such as degrasyn that can pharmacologically target constitutively expressed NF-kappaB and STAT3 in MCL cells may be useful therapeutic agents for MCL when administered together with bortezomib.
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PMID:Degrasyn potentiates the antitumor effects of bortezomib in mantle cell lymphoma cells in vitro and in vivo: therapeutic implications. 2060 45

Clinical, histological features and outcome of a cohort of patients with orbital and adnexal lymphoproliferative tumors were evaluated. Twenty-five cases in an oncologic referral center from 1995 to 2008, were included in the study. Each case had detailed immunophenotypic analysis using a panel of monoclonal antibodies (CD45, CD20, CD3, CD5, CD23, BCL2, BCL6, BCL10, Ki67, CD30, CD15, BCL1, Kappa, Lambda, CD138). Lesions were classified by using WHO (2008) lymphomas classification. Twenty-three patients were found to have primary and two secondary lymphomas. Histological subtypes were: 16 patients with marginal zone B cell lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma, four diffuse large B cell lymphomas, two mantle cell lymphomas, two follicular lymphomas, and one Hodgkin lymphoma. Among the 25 patients studied, 22 had localized stage. Extranodal marginal zone lymphoma was the most frequent type of primary orbital and adnexal lymphoma. In this study localized disease was observed in most cases, and distant spread of the lymphomas was infrequent.
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PMID:[Orbital and ocular adnexal lymphomas. Clinico-pathological correlation in 25 cases]. 2067 53


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