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Old 04-16-2007, 11:35 AM
Dross Dross is offline
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Default Massey researchers induce cell death in leukemia

Researchers from the Virginia Commonwealth University Massey Cancer Center today presented preclinical research at the American Association of Cancer Research's annual meeting suggesting the potential of a new combination treatment for chronic lymphocytic leukemiaterm (CLL).

In this study, led by Steven Grant, M.D., Massey's associate director of translational research, interactions between bortezomib and romidepsin (Gloucester Pharmaceuticals) and bortezomib with belinostat (aka PXD101 from CuraGen Corporation and TopoTarget A/S), were examined in human CLL cells isolated from five patients. Bortezomib dramatically potentiated the lethality of both agents in cells from four of five patients, while exerting additive effects in cells from one patient. Notably, pronounced lethality was observed following treatment of cells with very low concentrations of the agents.

Parallel studies conducted on two established CLL cell lines provided additional preclinical evidence that bortezomib interacts synergistically with both agents to induce cell death in human CLL cells. Romidepsin and belinostat are histone deacetylase (HDAC) inhibitors.

"To the best of our knowledge, this is the first report describing synergistic interactions between HDAC inhibitors and Bortezomib combinations in the setting of CLL," said Grant. "The findings of our study -- as well as the emerging body of preclinical and early clinical data suggesting interactions between HDAC inhibitors and bortezomib in other tumor cell types, particularly hematologic malignancies -- is certainly of interest and warrants further investigation as a potential therapeutic strategy in CLL."

Last edited by gdpawel : 07-08-2012 at 12:53 AM. Reason: post full article
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Old 02-20-2011, 03:31 PM
gdpawel gdpawel is offline
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Default Types of Cell Death

Following the description of apoptosis in the British Journal of Cancer in 1972, scientists around the world incorporated the concept of programmed cell death into their cancer research.

What is less understood is the fact that apoptosis is not synonymous with programmed cell death.

Programmed cell death is a fundamental feature of multicellular organism biology. Mutated cells incapable of performing their normal functions self-destruct in service of the multicellular organism as a whole.

While apoptosis represents an important mechanism of programmed cell death, it is only one of several cell death pathways.

Apoptotic cell death occurs with certain mutational events, DNA damage, oxidative stress and withdrawal of some growth factors particularly within the immune system.

Non-apoptotic programmed cell death includes: programmed necrosis, para-apoptosis, autophagic cell death, nutrient withdrawal, and subtypes associated with mis-folded protein response, and PARP mediated cell death.

While apoptotic cell death follows a recognized cascade of caspase mediated enzymatic events, non-apoptotic cell death occurs in the absence of caspase activation.

With the recognition of programmed cell death as a principal factor in carcinogenesis and cancer response to therapy, there has been a growing belief that the measurement of apoptosis alone will provide the insights needed in cancer biology.

This oversimplification underestimates the complexity of cell biology and suggests that cancer cells have but one mechanisms of response to injury. It has previously been shown that cancer cells that suffer lethal injury and initiate the process of apoptosis can be treated with caspase inhibitors to prevent caspase-mediated apoptosis.

Of interest, these cells are not rescued from death. Instead, these cells committed to death, undergo a form of non-apoptotic programmed cell death more consistent with necrosis. Thus, commitment to death overrides mechanism of death.

Labs that focus on measurements of caspase activation can only measure apoptotic cell death. While apoptotic cell death is of importance in hematologic cancers and some solid tumors, it does not represent the mechanism of cell death in all tumors.

This is why cell-based functional profiling labs measure all cell death events by characterizing metabolic viability at the level of cell membrane integrity, ATP content, or mitochondrial function.

While caspase activation is of interest, comparably easy to measure and useful in many leukemias and lymphomas, it does not represent cancer cell death in all circumstances and can be an unreliable parameter in many solid tumors.

Source: Cell Function Analysis
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