Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0079731 (B-cell lymphoma)
 16,671 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor-targeted delivery of a potent cytotoxic agent, calicheamicin, using its immunoconjugates is a clinically validated therapeutic strategy. Rituximab is a human CD20-specific chimeric antibody extensively used in B-NHL therapy. We investigated whether conjugation to calicheamicin can improve the anti-tumor activity of rituximab against human B-cell lymphoma (BCL) xenografts in preclinical models. BCL cells were cultured with rituximab or its calicheamicin conjugates and their in vitro growth was monitored. BCL cells were injected s.c. to establish localized xenografts in nude mice or i.v. to establish disseminated BCL in severe combined immunodeficient (scid) mice. I.p. treatment with rituximab or its calicheamicin conjugates was initiated and its effect on s.c. BCL growth or survival of mice with disseminated BCL was monitored. Conjugation of calicheamicin to rituximab vastly enhanced its growth inhibitory activity against BCL in vitro. Conjugation to calicheamicin had no deleterious effect on the effector functional activity of rituximab. Calicheamicin conjugated to rituximab with an acid-labile linker exhibited greater anti-tumor activity against s.c. BCL xenografts and improved survival of mice with disseminated BCL over that of unconjugated rituximab. Anti-tumor activities of rituximab conjugated to calicheamicin via an acid-stable linker were similar to that of unconjugated rituximab. Superior anti-tumor efficacy exhibited by a calicheamicin immunoconjugate of rituximab with an acid-labile linker over that of rituximab demonstrates the therapeutic potential of CD20-specific antibody-targeted chemotherapy strategy in the treatment of B-NHL.
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PMID:CD20-specific antibody-targeted chemotherapy of non-Hodgkin's B-cell lymphoma using calicheamicin-conjugated rituximab. 1716 Jun 82

Patients infected with human immunodeficiency virus (HIV) are at greater risk of developing non-Hodgkin lymphoma than the general population and aggressive B-cell lymphoma has become one of the most common of the initial acquired immunodeficiency syndrome (AIDS)-defining illnesses. This review considers the prognostic factors and new approaches to the treatment of patients with AIDS-related lymphoma (ARL). As highly active antiretroviral therapy (HAART) became available, the survival of many ARL patients has become comparable to that of HIV-negative patients. This is partly due to the decrease in the incidence of opportunistic infections and improved prognosis. Both developments can also be attributed to new treatment strategies for ARL, such as the use of effective infusional regimens, Rituximab combinations and high-dose therapy with autologous stem-cell transplantation for relapsed disease. However, unresolved issues persist, such as the optimal therapy for patients with Burkitt ARL or central nervous system involvement.
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PMID:Modern management of non-Hodgkin lymphoma in HIV-infected patients. 1722 46

Rituximab improves response to treatment and outcome for patients with CD20+ B-cell lymphoma. Herein, however, we report the occurrence of severe pulmonary complications shortly after rituximab infusion in three patients with the newly diagnosed Asian variant of intravascular lymphoma. It is suggested that patients with this subtype of lymphoma are monitored carefully for possible drug reactions during the use of rituximab.
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PMID:Severe pulmonary complications after initial treatment with Rituximab for the Asian-variant of intravascular lymphoma. 1722 54

Rituximab is the first antibody-based therapy approved in cancer. The role of this treatment for non-Hodgkin's lymphoma has evolved significantly since its introduction. We aimed to systematically review the literature on rituximab in non-Hodgkin's lymphoma and provide consensus guidelines as to the rational use of this agent. Validated methodology from the Cancer Care Ontario Program in Evidence-Based Care was applied. A comprehensive literature search was completed by reviewers from the Hematology Disease Site Group of Cancer Care Ontario. Data were abstracted from randomized controlled trials of rituximab-containing regimens for patients with non-Hodgkin's lymphoma. Twenty-three randomized controlled trials (RCTs) of rituximab-based therapy were analyzed. Consistent and clinically important benefits in progression-free and overall survival and were seen in the following settings: (1) addition of rituximab to combination chemotherapy for initial treatment of diffuse large B-cell lymphoma and other aggressive B-cell lymphomas; (2) addition of rituximab to combination chemotherapy for initial and subsequent treatment of follicular lymphoma and other indolent B-cell lymphomas; and (3) use of rituximab alone as extended maintenance therapy in patients with indolent B-cell lymphomas who have responded to initial treatment. The consensus opinion of the Hematology Disease Site Group is that rituximab is recommended for these indications.
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PMID:Rituximab in lymphoma: a systematic review and consensus practice guideline from Cancer Care Ontario. 1724 May 33

Malignant lymphoma is often accompanied by an autoimmune disorder. Here, we describe a 82-year-old woman with pure red cell aplasia (PRCA) complicated with relapsed diffuse large B-cell lymphoma. Primary treatment involving chemotherapy, continuous oral administration of prednisolone and a single infusion of rituximab was unsuccessful for both diseases, but the following treatments with 3 courses of rituximab alone for once a week dramatically improved the PRCA as well as the lymphoma. As PRCA complicated with lymphoma is rare, the ideal therapeutic strategy has not yet been established for it. Rituximab may be a good alternative for treating such cases.
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PMID:[Pure red cell aplasia successfully treated with rituximab in a patient with relapsed diffuse large B-cell lymphoma]. 1731 80

Rituximab is now routinely use in clinical practice for B cell lymphoma and chronic lymphocytic leukaemia treatment. Mechanisms of action of this monoclonal antibody are not fully understood. Antibody dependent cellular cytotoxicity (ADCC), complement dependent toxicity (CDC) and apoptosis have been all shown to play a role. But the prominence of each mechanism is considerably varying among the different reports, the studied cell lines and the experimental models. A lack of explanations still exists between the efficacy observed in vivo and the low reproducible cytotoxicity reproduced shown in vitro. Despite an intensive research, most of the mechanisms of resistance to rituximab are unknown.
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PMID:[Rituximab: mechanism of action and resistance]. 1733 89

Since rituximab, a chimeric monoclonal anti-CD20 antibody, was introduced into clinical practice in 1997, data regarding its benefit in terms of response rate, quality of response, progression-free survival and overall survival in B-cell lymphoid malignancies continues to expand. Rituximab has proven to be a relatively well-tolerated drug, with its major side effects being infusion related. Rituximab was approved initially by the US FDA and the European Medicines Agency for relapsed or refractory low-grade or follicular CD20+ B-cell non-Hodgkin lymphomas. Subsequently, its use has been extended to include first-line therapy in low-grade lymphoma as well as the treatment of more aggressive histological subtypes such as diffuse large B-cell lymphoma. In this article, we review the landmark trials that have impacted clinical practice in follicular and diffuse large B-cell lymphomas and the emerging data for use of rituximab as maintenance therapy in non-Hodgkin lymphoma.
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PMID:Rituximab and its role as maintenance therapy in non-Hodgkin lymphoma. 1733 47

Elevated expression of the antiapoptotic protein Bfl-1 (A1) was previously reported in several cancer cell lines. Recently, molecular profiling of large B-cell lymphoma identified Bfl-1 as a gene signature in 'OxPhos' diffuse large B-cell lymphoma subtype and in primary mediastinal large B-cell lymphoma, suggesting that in addition to Bcl-2, Bcl-xL and Mcl-1, Bfl-1 may be a relevant target in the design of new strategies for cancer therapy. Using short hairpin RNA strategy, we show here that Bfl-1 silencing in one lymphoblastoid B-cell line and in two diffuse large B-cell lymphoma cell lines potently induces their apoptosis and sensitizes those cell lines to anti-CD20 (Rituximab)-mediated cell death as well as to apoptosis induced by chemotherapeutic molecules such as doxorubicin, vincristine, cisplatin and fludarabine. These results demonstrate for the first time that Bfl-1 is an essential protein for survival of malignant B cells and suggest Bfl-1 may represent a potential target for future drug development against B cell lymphoma.
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PMID:Downregulation of Bfl-1 protein expression sensitizes malignant B cells to apoptosis. 1735 99

The positive regulatory domain I (PRDM1) is a master regulator in the differentiation of mature B lymphocytes to plasma cells. It has 2 isoforms, PRDM1alpha and PRDM1beta, and is regulated by the transcriptional regulator nuclear factor kappa (NF)-kappaB. PRDM1 protein expression was recently demonstrated in a subset of diffuse large B-cell lymphoma (DLBCL) with aggressive behavior, a type of lymphoma for which rituximab associated with chemotherapy (R-CHOP) is now widely indicated. Using laser microdissection combined with reverse transcription-polymerase chain reaction (RT-PCR) amplification, PRDM1 gene expression was assessed in 82 DLBCL patients. The results showed that both PRDM1alpha and PRDM1beta transcripts were expressed in microdissected lymphoma cells only in the non-germinal center B-cell-like (non-GCB) subtype of DLBCL. PRDM1beta gene expression was correlated with short survival time in the non-GCB patients treated with CHOP but not with R-CHOP. In vitro, B-lymphoma cells resistant to chemotherapy expressed PRDM1beta. Rituximab suppressed PRDM1beta expression, which was concomitant with NF-kappaB inactivation. The value of PRDM1beta expression as a prognostic marker in non-GCB DLBCL might thus be considered. This study confirms the efficiency of rituximab on DLBCL and allows a better understanding of one of its biologic actions.
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PMID:Rituximab plus CHOP (R-CHOP) overcomes PRDM1-associated resistance to chemotherapy in patients with diffuse large B-cell lymphoma. 1826 89

This is the first report of the combination of gemcitabine, cisplatin and methylprednisolone (GEM-P) with Rituximab (GEM-PR) for diffuse large B-cell lymphoma (DLBCL). Thirty-nine patients with relapsed or refractory DLBCL in this study received GEM-P with (n = 24) or without Rituximab (n = 15) 64% patients had Stage III/IV disease. The overall response rate (ORR) was 59% (95% CI 42.1-74.4); 11/39 (28%) patients attained complete response. Patients received a median of two cycles (1-4) of treatment. For GEM-PR group, the ORR was 67% (95% CI 45-84%) compared to 47% (95% CI 21-73%) in GEM-P alone. one-year progression-free survival was 51% (95% CI 28-69%) in GEM-PR group compared to 27% (95% CI 8-49%) in GEM-P alone (P = 0.04). GEM-P is an effective second-line regimen in patients with relapsed or refractory DLBCL and the addition of Rituximab appears to further improve outcomes.
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PMID:Gemcitabine, cisplatin and methylprednisolone (GEM-P) with or without Rituximab in relapsed and refractory patients with diffuse large B cell lymphoma (DLBCL). 1745 96


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