Bcl-2
Sep 18 2012
IMPROPER REGULATION OF BCL-2 PATHWAY IN TUMORS:
Bcl-2 protein is abbreviated on basis of chromosomal translocations for the B-cell lymphoma 2 is a major apoptosis regulatory protein and is seen to be associated with it in the follicular lymphoma. Bcl-2 protein along with its other family members keeps a tight check on balancing the cell growth and apoptosis of the cells by keeping an interaction with each other. Any disturbance in the homeostatic balance between apoptosis and growth of cells usually results in the aberrations associated with various types of cancers. Hence using the Bcl-2 inhibitors to achieve Bcl-2 inhibition seems to be an attractive and promising strategy for the treatment of many types of cancers. Different Bcl-2 antagonists are designed on the basis of this strategy among them some are showing promising results at the pre-clinical and clinical levels. As the decrease in apoptosis is a key feature of the development of some sort of cancer, so it was not very surprising to find an association between the Bcl-2 gene, breast cancer, melanoma, prostate cancer and lung carcinomas along with the neurodegenerative problems like autoimmune disorders and schizophrenia.
>Read the Full Post
( 0 ) Comments |
( 491 ) Read
Mar 13 2012
BCL-2 INHIBITION AND ITS IMPLICATIONS:
Bcl-2 family of proteins are a series of regulator proteins governing the pro-survival pathway. Characteristically Bcl-2 has been discovered to be over expressed in a variety of tumor types such small cell lung cancer, melanoma, prostate and breast cancer. The concept of targeted chemotherapy is to focus drug inhibition against a target that is over expressed in the cancer cell in comparison to normal cellular material; Bcl-2 is a clear target for inhibition. Over expression of this protein disrupts the regulation of the intrinsic apoptotic pathway, creating chemotherapeutic resistance. By inhibiting the sequestering of pro-apoptotic proteins by the Bcl-2 family (anti-apoptotic proteins) normal apoptotic processes can be utilized to trigger tumor cell death. Significantly there have been several now molecules introduced into the clinic in recent years which target Bcl-2 and have demonstrated clear benefits in chemotherapeutic action. One of these small molecules is ABT-737, while others are Navitoclax (ABT-263), Obatoclax (GX15-070) and TW-37.
>Read the Full Post
( 6 ) Comments |
( 690 ) Read
Mar 13 2012
INHIBITION OF BCL-2 PROTEINS:
Apoptosis is the natural system for the removal of cellular material from the body. This could be due to damage by invasion, age or injury. There are two mechanisms which regulate this process, the Intrinsic and the Extrinsic pathways. The extrinsic pathway is a cascade of signal originating from outside the cell via death receptors on the cellular membrane. The intrinsic pathway is initiated within the cell whereby pro-apoptotic proteins are released to activate the caspase cascade from the mitochondria. Part of the caspase cascade is the family of Bcl-2 proteins which regulate the process towards apoptosis or survival. Bcl-2 family consists of anti-apoptotic members such as Bcl-2, Mcl-1, Bcl-XL and Bcl2a1, other members are the pro-apoptotic proteins such as BAX, BAK, BAD, BIM, PUMA, BID, BIK, NOXA and BMF. In many forms of cancer it has been demonstrated that Bcl-2 is over expressed such as lung, breast, prostate, renal, ovarian and glioblastoma cancer, melanoma and leukemia are the highest report over expressers of Bcl-2.
>Read the Full Post
( 4 ) Comments |
( 592 ) Read
Mar 13 2012
ABT-263 – Introduction:
ABT-263 is a small molecule Bcl-2/Bcl-XL inhibitor marketed by Abbott laboratories under the generic name of Navitoclax. Similar in nature to ABT-737, also marketed by Abbott laboratories, ABT-263 inhibits the anti – intrinsic apoptotic pathway via the BH3 domain. Bcl-2/Bcl-XL bind with pro-apoptotic proteins (BID) with the single BH3 domain and thereby regulate the apoptotic process. However, it has been observed in numerous cancer types that Bcl-2 is over expressed which leads to the survival of cells that would normally be removed via apoptosis. ABT-263 Bcl-2 inhibitor have been demonstrated to be effective against small cell lung cancer xenographs, acute lymphoblastic leukemia and hematologic tumors.
>Read the Full Post
( 4 ) Comments |
( 710 ) Read
Mar 13 2012
Importance of Bcl-2 Pathway in Cancer:
The pro-survival protein Bcl-2 and its related family members activate pro-survival pathways in cancer that are often associated with uncontrolled proliferation of cancer cells. Apart from this direct effect, stress pathways are also reported to be converging with Bcl-2 signaling pathways which makes the development of various Bcl-2 inhibitors an attractive approach to target cancer by inducing mitochondrial apoptotic pathways.
>Read the Full Post
( 5 ) Comments |
( 542 ) Read
Jul 9 2011
The newest review which give a overview of the BCL-2 family proteins including detail data of bcl-2 proteins, the signal transduction related to the bcl-2 and Pharmacological Regulation of the Bcl-2 Proteins
>Read the Full Post
( 59 ) Comments |
( 548 ) Read
Mar 11 2011
A review which gives a systematic description of the relationship between bcl-2 and cancer.
>Read the Full Post
( 59 ) Comments |
( 510 ) Read
Mar 2 2011
A article about bcl-2 family proteins which is citied more than 3500.One of the most classical articles about bcl-2 family proteins which is published in science.
>Read the Full Post
( 59 ) Comments |
( 503 ) Read
