Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019829 (Hodgkin's disease)
30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined the expression of CD20 in normal canine peripheral blood mononuclear cells, normal canine spleen, and canine non-Hodgkin lymphoma (NHL) to determine the feasibility of using this antigen as a diagnostic aid and as a possible target for therapy. An antibody generated against a C-terminal (intracytoplasmic) epitope of human CD20 recognized proteins of 32-36 kd in normal and malignant canine lymphocytes. This antibody showed restricted membrane binding in a subset of lymphocytes in peripheral blood, in the B-cell regions from a normal canine spleen and lymph node, and in malignant cells from 19 dogs with B-cell NHL, but not from 15 dogs with T-cell NHL. The patterns of CD20 reactivity in these samples overlapped those seen using an antibody that recognizes canine CD79a. This anti-CD20 antibody is therefore suitable as an aid to phenotype canine NHL. In contrast, normal canine B cells were not recognized by any of 28 antibodies directed against the extracellular domains of human CD20 (including the chimeric mouse-human antibody Rituximab) or by any of 12 antibodies directed against the extracellular domains of mouse CD20. Thus, the use of CD20 as a therapeutic target will require the generation of specific antibodies against the extracellular domains of canine CD20.
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PMID:CD20 expression in normal canine B cells and in canine non-Hodgkin lymphoma. 1600 6

Rituximab is a monoclonal antibody directed against the CD20 surface antigen present on B lymphocytes. Following its application, B cells are rapidly and specifically depleted. Rituximab has been approved for the treatment of relapsed and therapy-refractory non-Hodgkin lymphoma and has been incorporated into numerous chemotherapy regimes with promising results. Eradication of auto-reactive B cell clones is the rationale for its application in a variety of autoimmune disorders including the pemphigus group where B cells are thought to play a critical role in the pathogenesis. Preliminary reports in autoimmune disorders are encouraging. Adverse effects are generally well controlled and although severe infections have been reported following rituximab, the overall risk does not seem to be significantly increased. In the pemphigus group, rituximab has been successfully employed in refractory cases and a recent study suggests that a single course induces long-term remission in this patient group.
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PMID:Anti-B- cell-directed immunotherapy (rituximab) in the treatment of refractory pemphigus--an update. 1604 47

Indolent Non-Hodgkin's lymphomas (NHL) are a group of slowly progressive immune system malignancies that cannot be cured with conventional treatment. Rituximab is an anti-CD20 monoclonal antibody that has recently become a part of the standard treatment of B-cell lymphoid malignancies. Here we present our experience in 25 patients with indolent NHL treated with rituximab with or without chemotherapy. Rituximab was administered at 3-4 week intervals in the standard dose of 375 mg/m2. 88% of the patients responded, 16 achieved a complete and 6 partial remission. Estimated 2-year actuarial survival is 63%. Response and survival rates were significantly better in patients with favorable prognosis (lower IPI score). Adverse effects related to rituximab occurred in 2 patients and were mild. Our results are completely comparable to previously reported studies and show that rituximab is effective and safe for the treatment of indolent B-cell NHL.
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PMID:[Rituximab in the treatment of indolent non-Hodgkin's lymphoma]. 1608 88

Rituximab is a genetically engineered chimeric monoclonal immunoglobulin (Ig)G1 antibody. It binds the CD20 trans-membrane surface antigen expressed by mature B cells but not by antibody secreting plasma cells, and removes the cells by activating complement, inducing cell-mediated lysis, and by apoptosis. Mainly used for the treatment of non-Hodgkin's lymphomas, rituximab has recently been tried with favourable responses in rheumatoid arthritis, systemic lupus erythematosus, and other chronic immunological diseases. Wegener's granulomatosis (WG) is a granulomatous vasculitis with high morbidity and mortality. It is thought that anti-neutrophil cytoplasmatic antibodies (ANCA) with specificity for proteinase 3 (PR3) are possibly involved in the pathogenesis of the disease. Conventional therapy with cyclophosphamide and corticosteroids generally succeeds in inducing remission, but relapses frequently follow. Among the biological agents, tumour necrosis factor-alpha (TNF-alpha) inhibitors have been tried with some success. Based on a case report we recently treated three refractory WG patients with rituximab and achieved almost complete but temporary remission. CD20+ cells disappeared rapidly in peripheral blood, only to rise prior to subsequent disease flares occurring at 34, 63, and 54 weeks, respectively (Figure 1). A new flare occurred in one patient at 86 weeks. At the end of the observation periods (54, 102, and 120 weeks), only one patient had proteinuria. Chest radiographs became normal in two patients, while infiltrates remained unchanged in the third. Granulomatous retro-orbital or sinus masses in two patients seemed unresponsive to therapy.
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PMID:Anti-CD20 therapy of treatment-resistant Wegener's granulomatosis: favourable but temporary response. 1613 30

Rituximab is a chimeric mouse-human monoclonal antibody, which binds to CD20, a B cell surface marker, leading to cell death by complement induced lysis and apoptosis. Since the introduction of this drug in the treatment of non-Hodgkin lymphoma, its applications have been extended to autoimmune diseases. This review summarizes the actual possible uses of this novel immune system targeted drug, and explains the mechanism of B cell depletion in autoimmune diseases.
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PMID:B cell depletion in autoimmune rheumatic diseases. 1613 9

Rituximab is a chimeric anti-CD20 monoclonal antibody. It has shown efficacy in patients with B-cell non-Hodgkin lymphoma and also in CD20-positive Hodgkin lymphoma. Recently, CD20-negative tumors have been described after Rituximab therapy. We report a 34-year-old man with a history of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), treated with different chemotherapy regimens, including anthracyclines and Rituximab. After 4 years in complete remission, he developed a CD20-negative T-cell-rich B-cell lymphoma (TCRBCL) presenting as multiple lung lesions. This case shows the difficulties in the diagnosis of CD20-negative lymphomas when the number of tumor cells is low and when they are found in a predominant T-cell context. Using anti-CD79a as a B-cell marker is mandatory to overcome the difficulties in identifying these tumors. Moreover, this case illustrates the usefulness of laser capture microdissection to obtain purified cell populations for molecular studies in lymphomas with relative paucity of tumor cells, as well as the need to analyze different IgH gene regions to decrease the rate of false-negative results in PCR clonality studies.
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PMID:CD20-negative T-cell-rich B-cell lymphoma as a progression of a nodular lymphocyte-predominant Hodgkin's lymphoma treated with rituximab: a molecular analysis using laser capture microdissection. 1616 Apr 85

Rituximab, a human-mouse, chimeric, monoclonal antibody that targets the B-cell CD20 antigen and causes rapid and specific B-cell depletion, is indicated for the treatment of low-grade or follicular, relapsed or refractory, CD20+ B-cell, non-Hodgkin lymphoma (NHL). We report the case of a middle-aged woman with psoriasis who experienced a partial sustained remission of her psoriasis after treatment with rituximab for NHL and discuss potential pathophysiologic mechanisms for this unexpected effect in a condition known to be mediated by T cells.
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PMID:Partial remission of psoriasis following rituximab therapy for non-Hodgkin lymphoma. 1626 62

Rituximab (chimeric anti-CD20 monoclonal antibody) is widely employed in the treatment of patients with B cell non-Hodgkin lymphoma (NHL). This agent has activity in both indolent and aggressive disease, alone and in combination with chemotherapy. Unfortunately, however, many patients develop resistant disease. Ongoing efforts to improve outcomes include changes in dose and schedule, as well as the use of other biologic agents or antibodies that may enhance activity when administered together with rituximab. A relatively new focus is the development of engineered anti-CD20 antibodies that are optimized for their capability to mediate antibody-mediated cellular cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC). Human or humanized structures have also been employed to potentially improve these attributes, as well as to improve on pharmacokinetics and immunogenicity. Other studies in NHL have clearly demonstrated that radiolabeled anti-CD20 antibodies (such as I-131 tositumomab and Y-90 ibritumomab tiuxetan) may be useful in relapsed and refractory disease, and have potential utility as part of initial treatment as well. Further studies of these modified anti-CD20 antibodies are ongoing in order to optimize their use for maximal clinical benefit.
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PMID:Targeting CD20 in follicular NHL: novel anti-CD20 therapies, antibody engineering, and the use of radioimmunoconjugates. 1630

Paraneoplastic pemphigus (PNP) is an autoimmune blistering disease with poor prognosis when associated with malignant neoplasm. We report the case of a patient with PNP associated with a CD20+ non-Hodgkin follicular lymphoma who was treated with Rituximab plus corticosteroids and short courses of cyclosporin. One and a half years after Rituximab therapy, oral ulcerations had cleared and oral methylprednisolone was slowly tapered down without further recurrences. In the course of the disease, the patient developed sepsis due to Listeria monocytogenes and viral infections by human herpes virus 1 and 3. At the end-stage of the disease she developed a cutaneous infection from Mycobacterium chelonae. The patient died 2 years and 7 months after the onset of PNP. Rituximab may be useful for PNP therapy, but further studies are necessary to confirm this hypothesis.
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PMID:Therapy of paraneoplastic pemphigus with Rituximab: a case report and review of literature. 1640 12

The present study investigated whether the expression of cellular Fas-associated death domain-like interleukin-1beta-converting enzyme (FLICE) inhibitory protein (cFLIP) conveys prognostic information in non-Hodgkin lymphomas (NHLs). cFLIP expression was quantified by immunohistochemistry and immunofluorescence in biopsy specimens from 86 NHL patients for whom clinical information was available. NHL malignancy was graded as high/intermediate or low according to the World Health Organization Classification of Lymphoid Neoplasms. cFLIP was positive in 23 of 45 high-/intermediate-grade NHLs and in 25 of 41 low-grade NHLs. Negative expression of cFLIP was associated with the presence of apoptotic cells in the tumour mass, regardless of the histotype and of the malignancy grade. In NHLs positive for cFLIP, 11 of 23 (48%) high-/intermediate-grade cases and 18 of 25 (72%) low-grade cases showed a bad outcome. In NHLs negative for cFLIP, only four of 22 (18%) high-/intermediate-grade patients and 12 of 16 (75%) low-grade patients achieved complete remission. All these correlations were statistically significant. The correlation of cFLIP expression with clinical outcome was independent of therapy, whether or not it included anti-CD20 antibody (Rituximab). The present findings strongly indicate that cFLIP is a reliable predictor of tumour progression and clinical prognosis in NHLs of low grade of malignancy.
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PMID:cFLIP expression correlates with tumour progression and patient outcome in non-Hodgkin lymphomas of low grade of malignancy. 1644 28


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