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

The Groupe d'Etude des Lymphomes de l'Adulte (GELA) has conducted several phase II and III studies in patients with aggressive lymphoma, diffuse large B-cell lymphoma (DLBCL), and T-cell lymphomas during the past 20 years, in France and Belgium. These studies, have demonstrated that the outcome of patients with DLBCL may be improved and that the standard CHOP (cyclophosphamide, doxorubicin HCl, vincristine [Oncovin], prednisone) regimen is not sufficient to cure a large number of patients. The first improvement was the demonstration of superiority of a dose-dense and dose-intense regimen, ACVBP (doxorubicin [Adriamycin], cyclophosphamide, vindesine, bleomycin, prednisone). The second improvement was made in young patients with poor-risk lymphoma by intensifying their treatment with high-dose therapy and autotransplant. The third and most significant improvement was in the results associated with the combination of rituximab (Rituxan) and chemotherapy. Current studies look at decreasing the. number of patients truly refractory to chemotherapy, decreasing relapse rate with rituximab maintenance, and finding an appropriate regimen for patients with T-cell lymphoma.
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PMID:Best treatment of aggressive non-Hodgkin's lymphoma: a French perspective. 1593 13

The most common subtype of aggressive non-Hodgkin's lymphoma is diffuse large B-cell lymphoma (DLBCL). Diffuse large B-cell lymphoma represents a heterogeneous entity, with 5-year overall survival rates ranging from 26% to 73%. Microarray gene expression studies have confirmed that biologically distinct subgroups exist within DLBCL, and can be correlated with outcome. Initial management is usually guided by stage of disease at presentation. Approximately 25% of patients with DLBCL present with limited-stage disease and are treated with combined-modality therapy (brief chemotherapy and involved-field radiation). Most patients present with advanced-stage disease and require treatment with an extended course of chemotherapy. The CHOP (cyclophosphamide, doxorubicin HCl, vincristine [Oncovin], prednisone) chemotherapy regimen has been the mainstay of therapy since its development in the 1970s, as more intensive chemotherapy regimens failed to show additional benefit. The era of monoclonal antibodies has transformed treatment practices for aggressive lymphoma and has led to a significant improvement in outcome. A randomized trial comparing the use of rituximab (Rituxan), a chimeric anti-CD20 IgG1 monoclonal antibody, combined with CHOP chemotherapy vs CHOP chemotherapy alone for elderly patients with advanced-stage DLBCL demonstrated a significant benefitfor the combination approach. This finding has now been confirmed in two additional randomized, controlled trials and a population-based analysis, making CHOP and rituximab the standard of care for all newly diagnosed patients with DLBCL. Despite this advance, newer therapies are needed and many are under active investigation. The insights gained from molecular techniques such as gene expression profiling should permit identification of additional lymphoma-specific therapeutic targets and the development of novel agents that take into account underlying biology and allow for greater tailoring of therapy.
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PMID:Treatment of aggressive non-Hodgkin's lymphoma: a north American perspective. 1593 15

Two novel lectins were purified from rhizomes of two sweet flag species, namely Acorus calamus (Linn.) and Acorus gramineus (Solandin Ait.) by affinity chromatography on mannose linked epoxy-activated Sepharose 6B. The apparent molecular mass of the lectins, as determined by gel filtration chromatography, was 56 kDa for ACL and 55 kDa for AGL. In SDS-PAGE, pH 8.3, both lectins migrated with a subunit molecular mass of 13.6 kDa and 13.5 kDa, respectively, under reducing and non-reducing conditions thus indicating the absence of disulphide linkages. Acorus lectins readily agglutinated rabbit, rat and guinea pig erythrocytes. Both ACL and AGL also reacted with RBCs from sheep, goat and human ABO blood groups after neuraminidase treatment. ACL and AGL were inhibited by mannose/glucose and their derivatives. The most effective inhibitor was methyl-alpha-D-mannopyranoside. Acorus lectins were stable up to 55 degrees C, did not require metal ions for their activity and were also affected by high concentrations of denaturants like urea, thiourea and guanidine-HCl. These lectins showed potent mitogenic activity towards mouse splenocytes and human lymphocytes. Both ACL and AGL also significantly inhibited the growth of J774, a murine macrophage cancer cell-line and to lesser extent WEHI-279, a B-cell lymphoma.
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PMID:Novel lectins from rhizomes of two Acorus species with mitogenic activity and inhibitory potential towards murine cancer cell lines. 1595 73

Burkitt lymphoma is a unique B-cell malignancy with a high proliferation rate and characteristic genetic changes involving the c-myc oncogene. Burkitt lymphoma is common in children but also occurs in adults, where distinction from diffuse large B-cell lymphoma may pose a problem. The development of brief, very intensive chemotherapy regimens has led to a very high cure rate in children with Burkitt lymphoma. The use of these regimens in adults, often in combination with the antibody rituximab (Rituxan), has also made the cure of a majority of adults possible. Burkitt lymphoma in adults cannot be treated effectively with the common regimens used for diffuse large B-cell lymphoma such as CHOP-R (cyclophosphamide, doxorubicin HCl, vincristine [Oncovin], prednisone, rituximab). Prompt diagnosis and initiation of appropriate therapy with attention to the possibility of tumor lysis syndrome are necessary for optimal results.
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PMID:Adult Burkitt lymphoma: advances in diagnosis and treatment. 1922 74

Enzastaurin (LY317615.HCl) is currently in a phase III registration trial for diffuse large B-Cell lymphoma and numerous phase II clinical trials. Enzastaurin suppresses angiogenesis and induces apoptosis in multiple human tumor cell lines by inhibiting protein kinase C (PKC) and phosphoinositide 3-kinase (PI3K)/AKT pathway signaling. PI3K/AKT pathway signaling liberates eukaryotic translation initiation factor 4E (eIF4E) through the hierarchical phosphorylation of eIF4E binding proteins (4E-BP). When hypophosphorylated, 4E-BPs associate with eIF4E, preventing eIF4E from binding eIF4G, blocking the formation of the eIF4F translation initiation complex. Herein, we show that enzastaurin treatment impacts signaling throughout the AKT/mTOR pathway leading to hypophosphorylation of 4E-BP1 in cancer cells of diverse lineages (glioblastoma, colon carcinoma, and B-cell lymphoma). Accordingly, enzastaurin treatment increases the amount of eIF4E bound to 4E-BP1 and decreases association of eIF4E with eIF4G, thereby reducing eIF4F translation initiation complex levels. We therefore chose to evaluate whether this effect on 4E-BP1 was involved in enzastaurin-induced apoptosis. Remarkably, enzastaurin-induced apoptosis was blocked in cancer cells depleted of 4E-BP1 by siRNAs, or in 4EBP1/2 knockout murine embryonic fibroblasts cells. Furthermore, eIF4E expression was increased and 4E-BP1 expression was decreased in cancer cells selected for reduced sensitivity to enzastaurin-induced apoptosis. These data highlight the importance of modulating 4E-BP1 function, and eIF4F complex levels, in the direct antitumor effect of enzastaurin and suggest that 4E-BP1 function may serve as a promising determinant of enzastaurin activity.
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PMID:Modulation of 4E-BP1 function as a critical determinant of enzastaurin-induced apoptosis. 2097 26

Non-Hodgkin's lymphoma (NHL) is the sixth-most common cancer in the UK, accounting for around 13,700 new cases every year. Until the late 1990s, treatment relied on intensive chemotherapy, such as CHOP (cyclophosphamide-doxorubicin HCl-vincristine [Oncovin]-prednisone). The use of standard CHOP therapy and its variations had resulted in poor five-year survival rates (as low as 26%), particularly in patients with aggressive NHL. Rituximab (Rituxan) was the first chimeric (mouse/human) monoclonal antibody approved for the treatment of NHL. It was approved by the US Food and Drug Administration in 1997 for indolent forms of NHL. It subsequently received EU approval in June 1998, and was licensed under the trade name Mabthera (Roche, Basel, Switzerland). It then went on to be approved for the first-line treatment of aggressive forms of NHL, such as diffuse large B-cell lymphoma (to be used in combination with CHOP or other anthracycline-based chemotherapy) in 2006. It is directed against the CD20 protein, an antigen found on the surface of B-cell lymphomas. With minimal toxicity, activity as a single-agent (for indolent forms of NHL) and safety when combined with chemotherapy (for aggressive forms), it represents great progress in this field. Here, we analyze how this antibody therapeutic was developed from basic molecular and cellular considerations through to preclinical and clinical evaluations and how it came to be a first-line treatment for NHL, and we discuss the impacts the advent of rituximab had on treatment outcomes for patients with DLBCL compared with the pre-rituximab era.
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PMID:How the discovery of rituximab impacted the treatment of B-cell non-Hodgkin's lymphomas. 3088 Nov 67