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Scientists build a synthetic peptide that overcomes cancer cells'survival defenses by 123wert sdfsf
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Scientists build a synthetic peptide that overcomes cancer cells'survival defenses by 123WERT SDFSF
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| Article Posted: 08/06/2012 |
| Article Views: 147 |
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Scientists build a synthetic peptide that overcomes cancer cells'survival defenses |
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Scientists at the Dana-Farber/Children's Hospital Cancer Centerhave developed an anti-cancer peptide that overcomes the stubbornresistance to chemotherapy and radiation often encountered incertain blood cancers when the disease recurs following initial treatment. The strategy could pave the way for much needed new therapies totreat relapsed and refractory blood cancers, which are difficult tocure because their cells deploy strong protein "deflector shields"to neutralize the cell death signals that chemotherapy agents usedagainst them initially, say the researchers. The prototype compound, called a "stapled BIM BH3 peptide," isdesigned to disable the cancer's defenses by hitting a family ofprotein targets that regulate cell death. In proof-of-concept studies in mice with transplanted,drug-resistant leukemia tumors, the compound alone suppressed cancer growth, and whenpaired with other drugs, showed synergistic anti-cancer activity,say researchers led by Loren Walensky, MD, PhD, ofDana-Farber/Children's Hospital Cancer Center.
Their paper has been posted online by the Journal of Clinical Investigation and will appear in the journal's June issue. Walensky is thesenior author and James LaBelle, MD, PhD, is the first author. A cell's "fate" - when and whether it lives or dies - depends on atug-of-war between pro-death and anti-death forces within the cellthat serve as a check-and-balance system to maintain orderlygrowth. The system is regulated by the BCL-2 family of proteins,which contains both pro-death and pro-survival members.
When cells are no longer needed or are damaged beyond repair, thebody activates pro-death BCL-2 proteins to shut down mitochondria -the power plants of the cell - resulting in an orchestratedcellular destruction known as apoptosis, or programmed cell death. Many cell-killing cancer treatments work by triggering these"executioner proteins" to cause tumor cells to commit suicide inthis fashion. But cancer cells can escape their death sentence -and even become immortal - by hyperactivating the survival arm ofthe family; these proteins intercept the executioner proteins andblock their lethal mission. "When cancers recur, they activate not just one type of survivalprotein, but many," explains Walensky, whose laboratory hasextensively studied the cell-death system and makes compounds tomanipulate it for research and therapeutic purposes. "It's as if relapsed cancers 'learned' from their initial exposureto chemotherapy such that when they come back, they put up avariety of formidable barriers to apoptosis," he adds.
"Toreactivate cell death in refractory hematologic cancers, we neednew pharmacologic strategies that broadly target these obstaclesand substantially lower the apoptotic threshold." When cancers specifically rely on one or two survival proteins,treating them with selective BCL-2 inhibitors can be very effectiveat eliminating the cancer cells' survival advantage. But relapsedcancers often evade such agents by deploying a battery of alternatesurvival proteins, so what's needed, Walensky says, are"next-generation" compounds that can block a wider range ofsurvival proteins without jeopardizing normal tissues. In the current research, the scientists built achemically-reinforced peptide containing the death-activating BH3domain of an especially potent killer protein, BIM, which is ableto tightly bind with and neutralize all of the BCL-2 familysurvival proteins. This 'stapled' peptide, which incorporates thenatural structure and properties of BIM BH3, not only disables thesurvival proteins, but also directly activates pro-death BCL-2family proteins in cancer cells, making them self-destruct.Importantly, non-cancerous cells and tissues were relativelyunaffected by the treatment.
"The diversity of BCL-2 family survival proteins blunts theanti-tumor activity of essentially all cancer treatments to somedegree," Walensky points out. "By using Nature's solution to broadtargeting of the BCL-2 pathway with a stapled BIM BH3 peptide, ourgoal is to eliminate cancer's protective force field and enable thearsenal of cancer treatments to do their job." Additional References Citations. I am a professional writer from Home & Garden, which contains a great deal of information about bassinet co sleeper , rabbit hutch designs, welcome to visit!
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