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An intensive short-term chemotherapy regimen has substantially prolonged the overall survival of Burkitt's lymphoma (BL) patients, which has been further improved by addition of rituximab. However, the inevitable development of resistance to rituximab and the toxicity of chemotherapy remain obstacles. We first prepared two BL cell lines resistant to rituximab-mediated CDC. Using a phosphorylation antibody microarray, we revealed that PI3K/AKT pathway contained the most phosphorylated proteins/hits, while apoptosis pathway that may be regulated by PKC displayed the greatest fold enrichment in the resistant cells. The PI3K/AKT inhibitor IPI-145 failed to reverse the resistance. In contrast, the pan-PKC inhibitor midostaurin exhibited potent antitumor activity in both original and resistant cells, alone or in combination with rituximab. Notably, midostaurin promoted apoptosis by reducing the phosphorylation of PKC and consequently of downstream Bad, Bcl-2 and NF-κB. Therefore, midostaurin improved rituximab activity by supplementing pro-apoptotic effects. In vivo, midostaurin alone powerfully prolonged the survival of mice bearing the resistant BL cells compared to rituximab alone treatments. Addition of midostaurin to rituximab led to dramatically improved survival compared to rituximab but not midostaurin monotherapy. Our findings call for further evaluation of midostaurin alone or in combination with rituximab in treating resistant BL in particular.
This article was published in the following journal.
Name: Cell death & disease
The outcome of Burkitt lymphoma has improved by over 90%. In this study, demographic characteristics and outcomes of 57 patients with Burkitt lymphoma treated with FAB LMB 96 regimen are presented.
Burkitt's lymphoma is a rarely encountered, aggressive B-cell lymphoma that is highly curable in children and young adults. In middle-aged and older adults, however, administering curative therapy may...
Rituximab plus chemotherapy has been shown to be effective in patients with advanced-stage, previously untreated follicular lymphoma; nevertheless, most patients will have a relapse. Combination immun...
Menorrhagia is a common gynecologic complaint among adolescents, which rarely is secondary to malignancy. Burkitt's lymphoma can mimic gynecologic malignancy, however it is rarely seen in adolescents....
Sporadic Burkitt's lymphoma can have a variety of clinical manifestations, including a constellation of gastrointestinal symptoms that can masquerade as other conditions and lead to a delay in diagnos...
This retrospective study is aimed at evaluating the safety and efficacy of rituximab-containing immunochemotherapy in adult patients with Burkitt's lymphoma (BL) or high-grade B-cell lymph...
Aim of the study is to assess the therapeutic activity and safety of the combination of Chlorambucil and Rituximab in MALT lymphomas and to determine whether the addition of Rituximab to C...
RATIONALE: Monoclonal antibodies such as rituximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemo...
RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help...
This study will evaluate the investigational drug Midostaurin in various doses given with ATRA and CLAG chemotherapy. Midostaurin is a FLT3 inhibitor that is activated or overexpressed in ...
A form of undifferentiated malignant LYMPHOMA usually found in central Africa, but also reported in other parts of the world. It is commonly manifested as a large osteolytic lesion in the jaw or as an abdominal mass. B-cell antigens are expressed on the immature cells that make up the tumor in virtually all cases of Burkitt lymphoma. The Epstein-Barr virus (HERPESVIRUS 4, HUMAN) has been isolated from Burkitt lymphoma cases in Africa and it is implicated as the causative agent in these cases; however, most non-African cases are EBV-negative.
B-cell lymphoid tumors that occur in association with AIDS. Patients often present with an advanced stage of disease and highly malignant subtypes including BURKITT LYMPHOMA; IMMUNOBLASTIC LARGE-CELL LYMPHOMA; PRIMARY EFFUSION LYMPHOMA; and DIFFUSE, LARGE B-CELL, LYMPHOMA. The tumors are often disseminated in unusual extranodal sites and chromosomal abnormalities are frequently present. It is likely that polyclonal B-cell lymphoproliferation in AIDS is a complex result of EBV infection, HIV antigenic stimulation, and T-cell-dependent HIV activation.
A murine-derived monoclonal antibody and ANTINEOPLASTIC AGENT that binds specifically to the CD20 ANTIGEN and is used in the treatment of LEUKEMIA; LYMPHOMA and RHEUMATOID ARTHRITIS.
CXCR receptors isolated initially from BURKITT LYMPHOMA cells. CXCR5 receptors are expressed on mature, recirculating B-LYMPHOCYTES and are specific for CHEMOKINE CXCL13.
The type species of LYMPHOCRYPTOVIRUS, subfamily GAMMAHERPESVIRINAE, infecting B-cells in humans. It is thought to be the causative agent of INFECTIOUS MONONUCLEOSIS and is strongly associated with oral hairy leukoplakia (LEUKOPLAKIA, HAIRY;), BURKITT LYMPHOMA; and other malignancies.