Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Revised European-American Lymphoma classification gives Burkitt-like lymphoma (BLL) provisional status, leaving unresolved the differential diagnosis with Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL). This study compared the biologic features of adult BLL and DLBCL. The phenotypic distinction between BLL and DLBCL was determined by immunohistochemical staining of frozen tissue from 13 patients with BLL and 55 patients with DLBCL by using an extensive antibody panel including Ki-67, CD10, CD11a/lymphocyte function-associated antigen 1alpha (LFA-1alpha), CD18/LFA-1beta, CD58/LFA-3, and CD54/intercellular adhesion molecule, CD8 for tumor-infiltrating cytotoxic T cells (T-TILs), CD44 homing receptor, and p53 and Bcl-2 oncogenic proteins. Compared with DLBCL, BLL had a higher proliferative rate (mean Ki-67, 88% versus 53%), greater expression of CD10 and p53 antigens, and decreased expression of Bcl-2. BLL cases had a consistent absence of one or more cell adhesion molecules (92% versus 27%), low T-TIL numbers, and absence of CD44 homing receptor (92% versus 14%). The t(8;14) translocation was identified in 80% of BLL cases, but no patients with BLL had the t(14;18) translocation. In a 10-year analysis, median survival of patients with BLL was 1.2 years, and that of patients with DLBCL was 2.5 years. Although the proportion of patients cured was similar in the 2 groups, BLL patients had an increased risk of early death. We conclude that BLL can be recognized by its combined morphologic and phenotypic features and that it represents a high-grade lymphoma much closer to BL than DLBCL. Retention of the BLL category or inclusion of BLL as a variant of BL is biologically and clinically more appropriate than absorbing the category of BLL into DLBCL. (Blood. 2001;97:3713-3720)
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PMID:The Burkitt-like lymphomas: a Southwest Oncology Group study delineating phenotypic, genotypic, and clinical features. 1138 7

In this study, we investigate the anticancer properties of an inert half-sandwich metal complex scaffold. UV melting experiments with duplex DNA and (1)H-NMR experiments with 9-ethylguanine reveal that the apoptotic ruthenium complex DW12 does not interact with DNA. On the other hand, diminishing the kinase inhibition properties of DW12 by methylating the maleimide nitrogen (DW12-Me) abolishes the anticancer activity. Furthermore, the incorporation of a fluorine into the pyridine moiety (NP309) improves the IC(50) value for glycogen synthase kinase 3 (GSK-3) and at the same time the cytotoxicity, implying that the anticancer activity correlates with the inhibition of GSK-3 and maybe other not yet identified kinases. We demonstrate in Burkitt-like lymphoma (BJAB) cells that NP309 is not necrotic but induces apoptosis and that this apoptosis is mediated by a loss of the mitochondrial membrane potential, caspase-9 processing, and is partly dependent on Bcl-2 expression. In addition, NP309 efficiently induces apoptosis in vincristine- and cytarabine-resistant human B-cell precursor cell lines.
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PMID:Inert ruthenium half-sandwich complexes with anticancer activity. 2002 18

A strategy for combinatorial parallel coordination chemistry is introduced that provides access to libraries of tris-heteroleptic ruthenium complexes in an economical fashion. Using this method, a library of 560 constitutionally unique, monocationic ruthenium complexes was synthesized, followed by a screening for anticancer activity and resulting in the identification of three hits with promising cytotoxic properties in HeLa cancer cells. A subsequent structure-activity relationship led to the discovery of the surprisingly simple anticancer complex [Ru(tBu(2)bpy)(2)(phox)]PF(6) (complex 1), with tBu(2)bpy = 4,4'-di-tert-buty-2,2'-bipyridine and Hphox = 2-(2'-hydroxyphenyl)oxazoline, displaying an LC(50) value in HeLa cells of 1.3 microM and 0.3 microM after incubation for 24 and 72 h, respectively. Complex 1 also shows remarkable antiproliferative and apoptotic properties at submicromolar concentrations in more clinically relevant Burkitt-like lymphoma cells. A reduction of the mitochondrial membrane potential by 1 indicates the involvement of the intrinsic pathway of programmed cell death. Further investigations reveal that 1 requires caspase-3 for the induction of apoptosis but is insensitive to the proapoptotic and antiapoptotic proteins Smac and Bcl-2, respectively.
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PMID:Discovery of a strongly apoptotic ruthenium complex through combinatorial coordination chemistry. 2068 87

Emerging resistances of tumors against multiple anti-cancer agents are a major concern in the chemotherapeutical treatment of various cancers. Clearly, this raises the need for novel therapeutics with new modes of action. Herein, we report on the favorable in vitro anti-proliferative properties of a phenanthridine-containing ReI(CO)3 complex (compound 1, also abbreviated LR-166) and identify major contributions to its mode of action. The complex induces apoptosis in low micromolar concentrations even in drug-resistant Burkitt-like lymphoma (BJAB) and leukemia (Nalm-6) cell lines with known overexpression of p-glycoproteins as was confirmed by measuring the amount of hypodiploid DNA via FACS Scan analysis. Importantly, a gene expression analysis in combination with toxicity studies on a number of modified cell lines (leukemia: NALM-6, lymphoma: BJAB, melanoma: MelHO) and the reduction of mitochondrial membrane potential (determined by adding JC-1 dye, followed by FACS analysis) confirmed the activation of both, the extrinsic and the intrinsic apoptotic pathway. Finally, the mechanism of action was shown not to be influenced by overexpression of the anti-apoptotic factor Bcl-2 in Mel-HO cells which are known to be resistant to a variety of drugs. All taken together, our experiments underscore the unique opportunities inherent in this novel lead structure of Re complexes to act as an effective chemotherapeutic agent in a combination therapy to overcome documented drug resistances in tumors.
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PMID:Resistance-breaking profiling and gene expression analysis on an organometallic ReI-phenanthridine complex reveal parallel activation of two apoptotic pathways. 3010 11