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)

Marginal zone lymphoma (MZL) and mantle cell lymphoma (MCL) belong to a subgroup of indolent B-cell lymphomas most commonly reported in the canine spleen. The goal of this study was to characterize the immunophenotype of splenic MZL and MCL in comparison to their human counterparts. Ten MCLs and 28 MZLs were selected based on morphology. A tissue microarray was generated, and expression of CD3, CD5, CD10, CD45, CD20, CD79a, Pax-5, Bcl-2, Bcl-6, cyclin D1, cyclin D3, MCL-1, MUM-1, and Sox-11 was evaluated. Neoplastic cells in all MCLs and MZLs were positive for CD5, CD20, CD45, CD79a, and BCL2 and negative for CD3, CD10, Bcl-6, cyclin D1, and cyclin D3. Positive labeling for Pax-5 was detected in 8 of 10 MCLs and 26 of 28 MZLs. Positive labeling for MUM-1 was detected in 3 of 10 MCLs, and 27 of 28 MZLs were positive for MUM-1. No MCLs but 8 of 24 MZLs were positive for MCL-1. Canine splenic MZL and MCL have a similar immunophenotype as their human counterparts. However, human splenic MCL overexpresses cyclin D1 due to a translocation. A similar genetic alteration has not been reported in dogs. In addition, in contrast to human MZL, canine splenic MZL generally expresses CD5. Following identification of B vs T cells with CD20 and CD3, a panel composed of BCL-2, Bcl-6, MUM-1, and MCL-1 combined with the histomorphological pattern can be used to accurately diagnose MZL and MCL in dogs. Expression of Bcl-2 and lack of MCL-1 expression in MCL may suggest a therapeutic benefit of BCL-2 inhibitors in canine MCL.
 ...
PMID:Immunophenotypic Characterization of Canine Splenic Follicular-Derived B-Cell Lymphoma. 3063 24

Apoptosis is one of the major mechanisms exhibited in response to cell death and induction of apoptosis in tumour cells signifies a potential target for cancer therapy. Bcl-2 family proteins play a key role in regulation of the apoptotic pathway. Bcl-2 overexpression is commonly associated with various cancers including breast cancer, prostate cancer, B-cell lymphomas and colorectal adenocarcinomas etc. Thus, Bcl-2 is a novel anti-cancer target attracting medicinal chemists across the globe. Research investigations underlying Bcl-2 target have resulted in the generation of small molecule inhibitors, named as 'BH3-mimetics' (Bcl-2 homology 3 mimetics). These drugs display binding to pro-survival Bcl-2 proteins resulting in actuation of apoptosis of cancer cells. The first BH3 mimetics discovered as an outcome of structure-based drug design and Nuclear Magnetic Resonance (NMR)-based screening was ABT-263, an N-acylsulfonamide analogue. Thrombocytopenia a major dose-limiting toxicity, associated with ABT-263 had provoked the invention of a highly selective Bcl-2 inhibitor venetoclax. Several Bcl-2 inhibitors as small molecules are under clinical development and the results indicated that these molecules alone or in combination could be of potential application in cancer therapy. This review summarizes an up to date knowledge of the available small molecule inhibitors, their discovery, synthesis, current clinical and pre-clinical status.
 ...
PMID:Current overview on the clinical update of Bcl-2 anti-apoptotic inhibitors for cancer therapy. 3149 78


<< Previous 1 2 3 4 5 6 7 8 9 10