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 non-Hodgkin's lymphomas (NHLs) comprise a heterogeneous collection of lymphoproliferative malignancies, which are most common in people aged over 55 years. Diffuse large B-cell lymphoma (DLBCL) is the most common type of NHL, accounting for approximately 30% of all new patients. Follicular lymphoma (FL) is the second most common NHL sub-type, and accounts for a further 22% of cases. While the incidence of most other cancers is decreasing, that of NHL is increasing steadily. During the 1970's and 1980's, worldwide NHL incidence rose by 3-4% per year. This rise has slowed in the 1990's, but an annual increase of 1-2% is still being recorded. Over the last five years, the introduction of monoclonal antibodies, and specifically the anti-CD20 monoclonal antibody, rituximab, has radically changed treatment of B-cell NHL. Rituximab is a genetically engineered chimeric mouse/human monoclonal antibody which binds to the transmembrane antigen, CD20, a non-glycosylated phosphoprotein, located on pre-B and mature B lymphocytes. This antigen is expressed on over 95% of all B cell NHLs, and on normal B cells, but not on haematopoietic stem cells, normal or malignant plasma cells. The Fc domain of rituximab recruits immune effector functions to mediate B cell lysis. Possible mechanisms of cytotoxicity include complement-dependent cytotoxicity (CDC) resulting from C1q binding, and antibody-dependent cellular cytotoxicity (ADCC) mediated by one or more of the Fcgamma receptors on the surface of granulocytes, macrophages and NK cells. It is also possible that the binding of rituximab to the CD20 antigen on the cell surface may directly induce apoptosis. For patients with both follicular and diffuse large B-cell NHL, several large scale prospective randomised trials have demonstrated prolongation of remission when rituximab is incorporated into first line treatment, and, in follicular lymphoma, as a component of salvage therapy. As a result of these studies, current European indications for rituximab include: the treatment of previously untreated patients with stage III-IV follicular lymphoma in combination with cyclophosphamide, vincristine and prednisone (CVP) chemotherapy; as maintenance therapy in patients with relapsed follicular lymphoma responding to induction therapy with chemotherapy or immuno-chemotherapy; the treatment of patients with diffuse large B cell NHL in combination with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy. This paper examines the evidence supporting the use of rituximab in these settings, and places its use into the context of standard clinical practice.
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PMID:The therapeutic use of rituximab in non-Hodgkin's lymphoma. 1720 82

Rituximab is a monoclonal chimeric antibody to the CD20 antigen, which has proven to be effective in the treatment of non-Hodgkin lymphomas. Recently, rituximab has also been employed in many non-malignant autoimmune disorders (i.e., idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura, connective tissue disorders and autoimmune hemolytic anemia) in which it has been used with the aim of interfering with the production of pathologic antibodies. Moreover, this agent has also shown to be effective in the treatment of acquired antibodies against factor VIII. Through a careful literature search, the current knowledge on rituximab therapy in adult acquired hemophilia A is presented in this review. Although mostly based on uncontrolled studies, the literature data suggest that this drug can be useful in the treatment of disorders of acquired inhibitors to factor VIII. However, large, prospective, randomized trials are needed to confirm these positive preliminary results.
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PMID:Rituximab in the treatment of adult acquired hemophilia A: a systematic review. 2650 21

Rituximab, a monoclonal chimeric antibody to the CD20 antigen, is an effective treatment for non-Hodgkin lymphomas. Moreover, rituximab has also shown efficacy in various autoimmune disorders. In this review, we will focus on the use of rituximab in childhood disorders of hemostasis associated with inhibitor formation. Although the results presented suggest that rituximab can be useful in the treatment of this subset of pediatric patients, most of the data come from isolated case reports or descriptions of small, uncontrolled series. Therefore, large, prospective, and randomized trials are needed to confirm the positive, preliminary results.
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PMID:Rituximab for the treatment of childhood chronic idiopathic thrombocytopenic purpura and hemophilia with inhibitors. 1731 49

Non-Hodgkin lymphomas (NHLs) comprise a diverse group of lymphatic malignancies of primarily B-cell origin, which are steadily increasing in prevalence worldwide. Approximately 63,190 new cases of NHL are expected to be diagnosed in the United States in 2007, representing 4% of all cancers. Further, the annual incidence rate of NHL in 2000-2004, estimated from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute, was 19.3 cases per 100,000 persons. Of these, the indolent NHLs, although initially responsive to a variety of therapeutic regimens, have a continuous relapsing nature and are essentially incurable. Over the past decade, the availability of monoclonal antibodies has revolutionized the treatment of patients with various types of NHL. To date, the most noteworthy agent of this type has been rituximab, an antibody directed against the CD20 antigen found on the majority of B-cell lymphomas. Rituximab is associated with improved and durable responses as a single agent and in combination with chemotherapy for patients with newly diagnosed or relapsed/refractory NHL. Recent data suggest an improvement in survival in recently diagnosed patients who have had access to rituximab therapy and provide new insights into the use of rituximab in frontline combination chemotherapy and as maintenance therapy. Other emerging therapeutics include new chemotherapeutics, small-molecule and monoclonal antibodies, radioimmunotherapy, apoptosis-inducing agents, and immunomodulators.
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PMID:Emerging treatments for indolent lymphoma. 1763 94

Mature T-cell neoplasms are relatively uncommon, accounting for approximately 10% of all non-Hodgkin lymphomas. This category of hematopoietic neoplasms is clinically aggressive and shows a poor response to therapy and shortened survival. The antigen CD20 has long been thought to be a specific marker for B-cell lineage and has been used to help differentiate T-cell and B-cell neoplasms. We present two cases of a rare subset of T-cell leukemia/lymphoma having a unique immunophenotype, both being CD20+. The significance of CD20 antigen in T-cell lymphomas is yet to be determined, but may allow treatment with novel therapeutic agents (eg, rituximab, a recombinant anti-CD20 monoclonal antibody).
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PMID:CD20 positive T-cell lymphoma/leukemia: a rare entity with potential diagnostic pitfalls. 1770 92

The aggressive lymphomas are potentially curable. The natural history of certain aggressive lymphomas has been altered by monoclonal antibody therapy. Targeted monoclonal antibody therapy to the CD20 antigen has altered the outcome of patients with diffuse large B-cell lymphoma in patients of all ages. Anti-CD20-based radioimmunoconjugates are being evaluated as radioimmunotherapy approaches in patients who have relapsed and in stem cell transplant settings. Antibody-directed therapy to the B-cell-specific antigen CD22 are ongoing. New approaches include different CD20 antibodies and an antibody to the CD40 antigen, which is a member of the tumor necrosis factor (TNF) receptor family, which is expressed on B-cells. Antibody therapy has been incorporated into CHOP (cyclophosphamide, adriamycin, vincristine, prednisone) therapy and other regimens such as EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) and HyperCVAD (cyclophosphamide, vincristine, adriamycin, dexamethasone). Single-agent anti-CD20 therapy is active in the post-transplantation lymphoproliferative disorders. T-cell antibodies are under evaluation in a number of T-cell lymphoproliferative disorders. Targeted therapy has changed the natural history of a number of aggressive non-Hodgkin lymphomas. This review will describe the contributions of antibody therapies to the treatment of these diseases.
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PMID:Antibody therapy in aggressive lymphomas. 1802 38

Type II mixed cryoglobulinemia (MC) is a systemic vasculitis, associated in most cases with hepatitis C virus (HCV) infection, sustained by proliferation of oligoclonal cells. Systemic B cell depletion and clinical remission can be achieved in non-Hodgkin lymphoma by human/mouse chimeric monoclonal antibody that specifically reacts with the CD20 antigen (rituximab). Similar effects could be expected in type II MC. Twelve patients, mean age 61.9 years (range 37-76), 11 with HCV infection genotype 2a2c (4 cases) or 1b (6 cases) and 3 (1 case) and symptomatic type II MC with systemic manifestations, including renal involvement, marrow clonal restriction, large necrotizing ulcers, and polyneuropathy, were considered eligible for rituximab therapy because of resistance or intolerance to conventional therapy or important bone marrow infiltration. Rituximab was administered intravenously at a dose of 375 mg/m2 on days 1, 8, 15, and 22. Two more doses were administered 1 and 2 months later. No other immunosuppressive drugs were added. Response was evaluated by assessing the changes in clinical signs, symptoms, and laboratory parameters. Levels of proteinuria, hematuria, erythrocyte sedimentation rate, cryocrit, rheumatoid factor, and IgM decreased while C4 values increased and HCV viral load remained stable during short- and medium-term observation. Bone marrow abnormalities were found to reverse to normal. Constitutional symptoms disappeared or ameliorated. No acute or delayed side effects were seen. Based on this experience and a number of reports published in the last 5 years, Rituximab appears to be a safe and effective therapeutic option in symptomatic patients with HCV-associated MC with signs of systemic vasculitis.
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PMID:Rituximab as a therapeutic tool in severe mixed cryoglobulinemia. 1827 Aug 64

The chimeric monoclonal antibody rituximab is the standard of care for patients with B-cell non-Hodgkin lymphoma (B-NHL). Rituximab mediates complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity of CD20-positive human B cells. In addition, rituximab sensitizes B-NHL cells to cytotoxic chemotherapy and has direct apoptotic and antiproliferative effects. Whereas expression of the CD20 antigen is a natural prerequisite for rituximab sensitivity, cell-autonomous factors determining the response of B-NHL to rituximab are less defined. To this end, we have studied rituximab-induced apoptosis in human B-NHL models. We find that rituximab directly triggers apoptosis via the mitochondrial pathway of caspase activation. Expression of antiapoptotic Bcl-xL confers resistance against rituximab-induced apoptosis in vitro and rituximab treatment of xenografted B-NHL in vivo. B-NHL cells insensitive to rituximab-induced apoptosis exhibit increased endogenous expression of multiple antiapoptotic Bcl-2 family proteins, or activation of phosphatidylinositol-3-kinase signaling resulting in up-regulation of Mcl-1. The former resistance pattern is overcome by treatment with the BH3-mimetic ABT-737, the latter by combining rituximab with pharmacologic phosphatidylinositol-3-kinase inhibitors. In conclusion, sensitivity of B-NHL cells to rituximab-induced apoptosis is determined at the level of mitochondria. Pharmacologic modulation of Bcl-2 family proteins or their upstream regulators is a promising strategy to overcome rituximab resistance.
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PMID:Targeting Bcl-2 family proteins modulates the sensitivity of B-cell lymphoma to rituximab-induced apoptosis. 1868 43

Lymphoma is a lymphoid cell cancer that originates in lymphoid tissues. Non Hodgkin (NHL) type represents 90% of cases. In Mexico, NHL constitutes the third most common cancer in males and the sixth among females. NHL treatment has achieved significant advances in the last decade and NHL is currently becoming a disease with a high probability of cure. Rituximab has become an alternative for the treatment of NHL. Rituximab is a monoclonal antibody that targets the CD20 antigen expressed in the mature malignant B cells. It induces NHL B cells destruction by complement-mediated citotoxicity, apoptosis and sensitization to the toxic effect of chemotherapy. Rituximab has revolutionized treatment results by offering patients with aggressive NHL a higher possibility of cure and in the case of the intractable forms of NHL it increases the disease free period. The standard treatment for a patient with NHL is rituximab-CHOP (immunotherapy). In addition, rituximab has pharmacoeconomic advantages as shown in various cost-utility and cost-effectiveness studies.
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PMID:[Current therapeutic advances in the treatment of non-Hodgkin lymphoma]. 1871 99

Rituximab is a monoclonal antibody specific for the CD20 antigen. Clinical factors associated with thrombocytopenia after administration of rituximab have only been reported as case reports. We have analysed retrospectively the change of platelet counts following the administration of rituximab in 253 patients with non-Hodgkin lymphoma (NHL). Correlations with clinical and laboratory parameters were assessed. A mean overall decrease in platelets was observed after rituximab infusion. A downward trend in platelet count of more than 30% was observed in 7.2% of the patients. The decline was observed when rituximab was given as a single agent or in combination with chemotherapy. The risk factors to develop a decline in platelets after infusion of rituximab were pre-existent thrombocytopenia, advanced lymphoma stage, bone marrow infiltration, splenomegaly, leukemic presentation, and Burkitt lymphoma histology. In conclusion, a decline in platelet count after administration of rituximab was observed in patients with NHL, mainly those with pre-existing thrombocytopenia.
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PMID:Rituximab-associated changes in platelet count in patients with non-Hodgkin lymphoma. 1902 Oct 44


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