Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:A9QXG9 (bcl-2)
 7,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One limitation of ASCT is the potential reinfusion of tumor cells contaminating PBSC. The Eligix B cell SC system consists of high-density microparticles coated with anti-B cell antibodies. To determine if this system eliminates B cells and lymphoma cells from PBSC, immunocytochemistry and PCR of the bcl-2/IgH rearrangement were performed, and correlated with patient outcome after ASCT. Eligible patients (n=29) had relapsed or transformed follicular NHL with bone marrow involvement <20%, and all lymph nodes <5 cm. PBSCs were mobilized with cyclophosphamide/G-CSF (n=21), and patients were conditioned with cyclophosphamide, carmustine and etoposide. Using immunocytochemistry on PBSC, the median number of CD20+ cells pre-purge was 310/10(6) (range 0-16692) and post-purge was 0.75/10(6); the median log B cell depletion was 2.7 (range 1.4-3.9). B cell depletion correlated with PFS after ASCT (P=0.06). Of 17 available samples for PCR, only four had a detectable t(14;18) breakpoint. After purging, all four remained PCR+; two had a 1-3 log depletion of lymphoma cells. At median follow-up of 18 months, 10 patients, including five infused with PCR-negative PBSC, have had disease progression. The paucity of PCR-informative patients, possibly related to in vivo rituximab therapy, limited the utility of minimal residual disease as a surrogate marker of clinical outcome.
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PMID:Ex vivo B cell depletion using the Eligix B Cell SC system and autologous peripheral blood stem cell transplantation in patients with follicular non-Hodgkin's lymphoma. 1313 Mar 15

The regulation of apoptosis is an important potential target for anticancer therapy. The mitochondrial Bcl-2 protein inhibits apoptosis and is therefore an important mediator of resistance to treatment with traditional cytotoxic chemotherapy, radiotherapy and monoclonal antibody therapy. Oblimersen (Genasense, Aventis Pharmaceuticals / Genta Inc) is a 18mer antisense-oligonucleotide (ASO), which specifically binds to the first 6 codons of the human bcl-2 mRNA, resulting in degradation and destruction of the mRNA by RNAse H. Subsequently there is a significant decrease of bcl-2 translation. A growing number of preclinical and clinical studies suggests that the combination of cytotoxic therapy with Oblimersen results in synergistic anticancer efficacy in many hematologic and solid tumors. Due to its low toxicity profile, oblimersen is an ideal combination partner with conventional chemotherapy. Three randomized phase-III trials (malignant melanoma, chronic lymphocytic leukemia, multiple myeloma) have recently finished recruitment. The results of these studies will be available by the end of 2003. Based on preclinical data, a lot of nonrandomized phase-II studies on several different tumor types like AML, CML, NHL, prostate cancer and breast cancer are underway. The manipulation of proapoptotic and antiapoptotic factors in favor of proapoptotic factors by inhibition of the bcl-2 protein translation in order to enhance the efficacy of anticancer treatments represents a promising new treatment concept in oncology.
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PMID:[Proapoptotic therapy with oblimersen (bcl-2 antisense oligonucleotide)--review of preclinical and clinical results]. 1471 45

The addition of rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy results in significant improvement in clinical outcome for individuals with non-HIV-associated aggressive B-cell lymphoma. To assess the potential risks and benefits of the addition of rituximab to CHOP for HIV-associated non-Hodgkin lymphoma (HIV-NHL) 150 patients receiving CHOP for HIV-NHL were randomized (2:1) to receive 375 mg/m(2) rituximab with each chemotherapy cycle (n = 99) or no immunotherapy (n = 50) in a multicenter phase 3 trial. The complete response rate (CR + CRu) was 57.6% for R-CHOP and 47% for CHOP (P = .147). With a median follow-up of 137 weeks, time to progression, progression-free survival, and overall survival times were 125, 45, and 139 weeks, respectively, for R-CHOP and 85, 38, and 110 weeks, respectively, for CHOP (P = not significant, all comparisons). Treatment-related infectious deaths occurred in 14% of patients receiving R-CHOP compared with 2% in the chemotherapy-alone group (P = .035). Of these deaths, 60% occurred in patients with CD4 counts less than 50/mm(3). Progression-free survival was significantly influenced by CD4(+) count (P < .001) and International Prognostic Index score (P = .022), but not bcl-2 status. The addition of rituximab to CHOP in patients with HIV-NHL may be associated with improved tumor responses. However, these benefits may be offset by an increase in infectious deaths, particularly in those individuals with CD4(+) lymphocyte counts less than 50/mm(3).
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PMID:Rituximab does not improve clinical outcome in a randomized phase 3 trial of CHOP with or without rituximab in patients with HIV-associated non-Hodgkin lymphoma: AIDS-Malignancies Consortium Trial 010. 1655 92

Follicular lymphoma (FL) is characterized by the presence of a t(14;18) chromosomal translocation that results in overexpression of bcl-2 protein. Bcl-2/IgH gene rearrangement is detected in 80-90% of follicular lymphomas in Western countries. The aim of this study was to analyze the bcl-2/IgH rearrangement in FL lymphoma patients in Serbia, by PCR technique, correlate molecular findings with clinical characteristics and outcome and assess the prognostic significance of these rearrangements. One hundred-seven patients (median age, 54 years; male/female ratio:60/47) diagnosed with FL were included in the study. DNA samples were obtained from paraffin embedded lymphoid tissue of patients. Bcl-2/IgH rearrangement was assessed for the major breakpoint region (MBR), 5' MBR and the minor cluster region (mcr) breakpoints by PCR technique. We detected a t(14;18) in 81.3% (87/107) of patients. The distribution of bcl-2-IgH rearrangement was as follows: 88,5% (77/87) in MBR breakpoint, 10,35% (9/87) in 5' MBR, whereas mcr bcl-2-IgH rearrangement was observed in one patient (1.15%). No rearrangements were detected in remaining 20 patients (18.7%). This is the first analyses of the frequency of the bcl-2/IgH gene rearrangement in Serbian FL patients, as well as in Eastern European countries. There was no correlation between presence of bcl-2/IgH gene rearrangement and clinical outcome of disease. Incidence of bcl-2/IgH gene rearrangement in Serbian FL patients is relatively high, and similar to frequency in Western countries. Presence of this rearrangement in tumor tissue is not of prognostic significance.
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PMID:Molecular characteristics and prognostic significance of Bcl-2/IgH gene rearrangement in Serbian follicular lymphoma patients. 1866 53


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