A research group from the Dana-Farber Cancer Institute, led by Dr. Loren Walensky, developed a compound modeled directly from the pro-apoptotic the death domain of BCL-2, the BIM BH3 domain. This compound, known as a stapled BIM BH3 peptide, was found to competitively bind with anti-apoptotic proteins and led to enhanced apoptosis in cancer cells. They also showed that tumor growth in mice was suppressed by the stapled BIM BH3 compound and that the new compound worked synergistically with other with pharmaceutical agents that promote apoptosis. The potential therapeutic effects of stapled BIM BH3 were further shown by activation of cell death in an acute myeloid leukemia tumor model in mice with little side effects on surrounding tissue. Their study presents a new formulation of a BH3 mimetic that has broad BCL-2 family targeting and may provide significant clinical benefit.
###
TITLE:
A stapled BIM peptide overcomes apoptotic resistance in hematologic cancers
AUTHOR CONTACT:
Loren Walensky
Dana-Farber Cancer Institute, Boston, MA, USA
Phone: 617-632-6307; Fax: 617-582-8240; E-mail: loren_walensky@dfci.harvard.edu
ACCOMPANYING COMMENTARY
TITLE:
Therapeutic potential of a peptide targeting BCL-2 cell guardians in cancer
AUTHOR CONTACT:
Jerry Adams
The Walter & Eliza Hall Institute, Melbourne, UNK, AUS
Phone: 61-3-93452491; Fax: 61-3-93470852; E-mail: adams@wehi.edu.au
Marked for destruction: Newly developed compound triggers cancer cell death
2012-05-28
(Press-News.org) The BCL-2 protein family plays a large role in determining whether cancer cells survive in response to therapy or undergo a form of cell death known as apoptosis. Cells are pressured toward apoptosis by expression of pro-apoptotic BCL-2 proteins. However, cancer cells respond to therapy by increasing expression of anti-apoptotic proteins, which bind and neutralize pro-apoptotic family members and mediate therapeutic resistance. Therefore, development of therapeutic strategies to neutralize resistance to apoptosis will be critical to clinical improvements.
ELSE PRESS RELEASES FROM THIS DATE:
JCI early table of contents for May 24, 2012
2012-05-28
GENE THERAPY
Gene therapy can correct forms of severe combined immunodeficiency
Severe combined immunodeficiency is defect in the immune system that results in a loss of the adaptive immune cells known as B cells and T cells. Mutations in several different genes can lead to the development of severe combined immunodeficiency, including mutation of the adenosine deaminase (ADA) gene. Traditional treatment options, such as enzyme replacement therapy, are of limited efficacy, but bone marrow transplant from a compatible donor leads to a better response. A recent clinical ...
A boost in microRNA may protect against sepsis and other inflammatory diseases
2012-05-28
BOSTON, MA—Acute inflammatory diseases, such as sepsis, as well as chronic inflammatory diseases like diabetes and arthritis, develop as a result of sustained inflammation of the blood vessel wall. Researchers at Brigham and Women's Hospital (BWH) have discovered that a microRNA (small, non-coding RNA molecule) called miR-181b can reduce the inflammatory response that is responsible for such diseases.
The findings, by researchers led by Mark Feinberg, MD from BWH and Harvard Medical School, will pave the way for new targets in the development of anti-inflammatory therapies. ...
Nuisance seaweed found to produce compounds with biomedical potential
2012-05-28
A seaweed considered a threat to the healthy growth of coral reefs in Hawaii may possess the ability to produce substances that could one day treat human diseases, a new study led by scientists at Scripps Institution of Oceanography at UC San Diego has revealed.
An analysis led by Hyukjae Choi, a postdoctoral researcher in William Gerwick's laboratory at Scripps, has shown that the seaweed, a tiny photosynthetic organism known as a "cyanobacterium," produces chemical compounds that exhibit promise as anti-inflammatory agents and in combatting bacterial infections. The ...
Chronic pain is relieved by cell transplantation in lab study
2012-05-28
Chronic pain, by definition, is difficult to manage, but a new study by UCSF scientists shows how a cell therapy might one day be used not only to quell some common types of persistent and difficult-to-treat pain, but also to cure the conditions that give rise to them.
The researchers, working with mice, focused on treating chronic pain that arises from nerve injury -- so-called neuropathic pain.
In their study, published in the March 24, 2012 issue of Neuron, the scientists transplanted immature embryonic nerve cells that arise in the brain during development and ...
Gourmet butterflies speed north
2012-05-28
A new study led by scientists in the Department of Biology at the University of York has shown how a butterfly has changed its diet, and consequently has sped northwards in response to climate change.
Their study is published in the latest issue of Science.
The researchers found that warmer summers have allowed the Brown Argus butterfly to complete its life cycle by eating wild Geranium plants. Because the Geraniums are widespread in the British countryside, this change in diet has allowed the butterfly to expand its range in Britain at a surprisingly rapid rate. Over ...
The cells' petrol pump is finally identified
2012-05-28
Our cells breathe and digest, as does the organism as a whole. They indeed use oxygen to draw the energy contained in the nutrients they ingest, before discarding the waste, as carbon dioxide and water. Glucose is a preferred nutrient for the cells. Its digestion occurs in the cytoplasm, in the absence of oxygen, and leads to the formation of pyruvate and a small amount of energy. Pyruvate is then carried into mitochondria, the cell's power plants, for a complete burning, thus providing a maximal energetic yield.
A mediocre energetic yield in tumor cells
'As opposed ...
CWRU class earns Science magazine prize for innovation
2012-05-28
Science magazine has awarded a prize for Inquiry-Based Instruction to a Case Western Reserve University class that melds biology, computer modeling, mathematical analysis and writing.
"Dynamics of Biological Systems," taught by Biology Professor Hillel Chiel and three graduate assistants, abandons traditional lectures altogether in favor of learning by doing. The teachers call the class an example of the use of the continual improvement model in education.
In it, Chiel pairs biology majors with engineering, physics or math majors, and has them concentrate on building ...
First direct observation of oriented attachment in nanocrystal growth
2012-05-28
Through biomineralization, nature is able to produce such engineering marvels as mother of pearl, or nacre, the inner lining of abalone shells renowned for both its iridescent beauty and amazing toughness. Key to biomineralization is the phenomenon known as "oriented attachment," whereby adjacent nanoparticles connect with one another in a common crystallographic orientation. While the importance of oriented attachment to biomineral properties long has been recognized, the mechanism by which it occurs has remained a mystery. With a better understanding of oriented attachment ...
Nanoparticles seen as artificial atoms
2012-05-28
VIDEO:
Berkeley Lab researchers at the National Center for Electron Microscopy recorded real-time observations of nanocrystal growth that support the theory of nanoparticles acting like artificial atoms. This electron microscopy movie...
Click here for more information.
In the growth of crystals, do nanoparticles act as "artificial atoms" forming molecular-type building blocks that can assemble into complex structures? This is the contention of a major but controversial ...
Knowing genetic makeup may not significantly improve disease risk prediction
2012-05-28
Boston, MA —Harvard School of Public Health (HSPH) researchers have found that detailed knowledge about your genetic makeup—the interplay between genetic variants and other genetic variants, or between genetic variants and environmental risk factors—may only change your estimated disease prediction risk for three common diseases by a few percentage points, which is typically not enough to make a difference in prevention or treatment plans. It is the first study to revisit claims in previous research that including such information in risk models would eventually help doctors ...