Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers develop new method for fighting leukemia

18.01.2007
Researchers at Virginia Commonwealth University's Massey Cancer Center have created a new method to improve the antileukemic activity of a novel agent that triggers programmed cell death, a development that could lead to more effective strategies for fighting leukemia and other malignancies.

The cell death process, or apoptosis, is characteristically impaired in cancer cells. The process is regulated by a large family of proteins that either promotes or inhibits cell death. Recently, considerable attention has focused on the development of agents that inhibit the actions of antiapoptotic members of this family.

One such agent, known as ABT-737, potently blocks the pro-survival effects of two proteins, Bcl-2 and Bcl-xL, according to Steven Grant, M.D., Massey's associate director for translational research and co-leader of the cancer center's cancer cell biology program. Grant is senior author of the study, which is published in the Jan. 15 issue of the journal Cancer Research.

In laboratory experiments, ABT-737 has been shown to be very effective in killing tumor cells. However, this agent is unable to block the actions of another anti-apoptotic family member, Mcl-1, and it has been found that increased expression of Mcl-1 in tumor cells significantly reduces the anti-tumor effectiveness of ABT-737.

... more about:
»ABT-737 »Mcl-1 »leukemia

Grant and colleagues demonstrated that interventions that reduce levels of Mcl-1 in leukemia cells dramatically increase the effectiveness of ABT-737. Specifically, they employed an agent called roscovitine to block the synthesis of Mcl-1 at the RNA level. Grant said that because Mcl-1 is a very short-lived protein, disrupting its synthesis rapidly lowers Mcl-1 levels.

Grant's team found that the simultaneous reduction in Mcl-1 expression in conjunction with disruption of the anti-apoptotic actions of Bcl-2 and Bcl-xL by ABT-737 resulted in the marked activation of an important pro-apoptotic protein known as Bak. Grant said that when Bak is freed from its constraints by these actions, it cooperates with other pro-death proteins to induce mitochondrial damage, culminating in the dramatic onset of apoptosis.

"Our findings are significant because we were able to employ pharmacologic agents to recapitulate the death process that occurs in normal cells, and which is impaired in their neoplastic counterparts," said Grant. "These findings could also have significant translational implications for the treatment of leukemia and potentially other malignancies."

"For example, analogs of roscovitine have recently entered the clinic, and a number of other agents capable of reducing Mcl-1 levels in tumor cells are currently being developed," he said.

Based upon the findings of Grant's group, regimens combining such agents with Bcl-2 antagonists like ABT-737 could represent a particularly effective treatment strategy in leukemia and various other malignancies.

This work was supported by grants from the National Institutes of Health, the Leukemia and Lymphoma Society of America, and the Department of Defense.

Grant, a professor of medicine and the Shirley Carter and Sture Gordon Olsson Professor of oncology, worked with a team that included: Shuang Chen, Ph.D., Yun Dai, Ph.D., and Hisashi Harada, M.D., Ph.D., all in the VCU Department of Medicine; and Paul Dent, Ph.D., a professor in the VCU Department of Biochemistry.

Sathya Achia-Abraham | EurekAlert!
Further information:
http://www.vcu.edu
http://www.massey.vcu.edu

Further reports about: ABT-737 Mcl-1 leukemia

More articles from Life Sciences:

nachricht Zebrafish's near 360 degree UV-vision knocks stripes off Google Street View
22.06.2018 | University of Sussex

nachricht New cellular pathway helps explain how inflammation leads to artery disease
22.06.2018 | Cedars-Sinai Medical Center

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Temperature-controlled fiber-optic light source with liquid core

In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.

Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...

Im Focus: Overdosing on Calcium

Nano crystals impact stem cell fate during bone formation

Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...

Im Focus: AchemAsia 2019 will take place in Shanghai

Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.

Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...

Im Focus: First real-time test of Li-Fi utilization for the industrial Internet of Things

The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.

Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.

Im Focus: Sharp images with flexible fibers

An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.

Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Munich conference on asteroid detection, tracking and defense

13.06.2018 | Event News

2nd International Baltic Earth Conference in Denmark: “The Baltic Sea region in Transition”

08.06.2018 | Event News

ISEKI_Food 2018: Conference with Holistic View of Food Production

05.06.2018 | Event News

 
Latest News

Graphene assembled film shows higher thermal conductivity than graphite film

22.06.2018 | Materials Sciences

Fast rising bedrock below West Antarctica reveals an extremely fluid Earth mantle

22.06.2018 | Earth Sciences

Zebrafish's near 360 degree UV-vision knocks stripes off Google Street View

22.06.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>