Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

2-Drug Combo More Effective in Treating Sarcomas, Moffitt Cancer Center Study Shows

10.04.2013
Researchers at Moffitt Cancer Center and colleagues at the University of South Florida have found that when given together, a two-drug combination acts synergistically in test animals modeled with sarcoma tumors.
They report that the drug combination of MK-1775 and gemcitabine resulted in a 70 percent decrease in the tumor volume when compared to receiving one drug or the other.

Their study was published in the March 8 online edition of PLOS ONE.

“Sarcomas are rare tumors affecting both children and adults, but sarcomas account for a greater number of pediatric cancers than adult,” said study lead author Soner Altiok, M.D., Ph.D., associate member of the Chemical Biology and Molecular Medicine Program. “Sarcoma response rates to standard chemotherapies have been low, drug toxicity has been high, and improvement in overall survival, especially in metastatic disease, has been negligible. New drugs are needed.”

Sarcomas are cancers that result from transformed cells in one of a number of tissues, including bone, cartilage, fat, muscle and vascular tissues. Sarcomas are different from carcinomas, such as breast, colon and lung cancers.

Researchers from Moffitt’s Chemical Biology and Molecular Medicine and Sarcoma programs had previously collaborated in testing MK-1775’s ability to inhibit Wee1, a protein known to regulate cell size and initiate cell division, an important step in the development of sarcoma. Wee1 plays a role in determining the time at which cell division begins. The researchers found that inhibition of Wee1 by MK-1775 induced cell death in sarcoma tumors.

“Inhibition of the pathways critical to tumor cell survival by molecularly targeted therapy represents an opportunity to reverse the biological basis of tumor formation,” Altiok explained.
To further prove that inhibition of Wee1 by MK-1775 leads to cell death in sarcomas cells, the researchers performed additional studies, including studies on sarcomas-related mutations, such as the p53 gene. They also showed that MK-1775 was an active inhibitor of Wee1 regardless of the p53 mutation status of the tumors in the cell lines tested.

“The toxic effect of Wee1 inhibition on sarcoma cells appeared to be independent of p53 mutation status following our testing sarcoma cell lines with different p53 mutations,” Altiok said. “All of them were highly sensitive to MK-1775, suggesting that Wee1 inhibition may represent a novel approach in the treatment of sarcomas. But p53 status was not predictive of response to MK-1775 as a single agent.”

Because of the success of that previous research, in the new study the Moffitt team investigated the benefits of MK-1775 alone compared to MK-1775 in combination with gemcitabine, a standard chemotherapy drug. They tested the combination in a number of sarcoma cell lines derived from patient tissues and then in animals modeled with osteosarcoma (bone sarcoma).
“The combination of MK-1775 and gemcitabine demonstrated a synergistic effect in sarcoma cells,” explained Altiok. “MK-1775 alone caused tumor cell damage, but when used in combination with gemcitabine, there was increased cell death.”

When the research team tested the combination in laboratory animals, they found that gemcitabine alone inhibited 40 percent of tumor growth. MK-1775 alone inhibited 50 percent of tumor growth. However, MK-1775 and gemcitabine together inhibited 70 percent of tumor cell growth.
“Our data demonstrated that MK-1775 alone and in combination with gemcitabine induces significant cell death in high-grade osteosarcoma cells,” concluded the authors. “This finding lays an important foundation for future clinical trials with MK-1775, which is a well-tolerated, readily available targeted drug.”

About Moffitt Cancer Center
Located in Tampa, Moffitt is one of only 41 National Cancer Institute-designated Comprehensive Cancer Centers, a distinction that recognizes Moffitt’s excellence in research, its contributions to clinical trials, prevention and cancer control. Since 1999, Moffitt has been listed in U.S. News & World Report as one of “America’s Best Hospitals” for cancer. With more than 4,200 employees, Moffitt has an economic impact on the state of nearly $2 billion. For more information, visit MOFFITT.org, and follow the Moffitt momentum on Facebook, twitter and YouTube.

Media release by Florida Science Communications

Kim Polacek | EurekAlert!
Further information:
http://www.moffitt.org

More articles from Health and Medicine:

nachricht Study suggests possible new target for treating and preventing Alzheimer's
02.12.2016 | Oregon Health & Science University

nachricht The first analysis of Ewing's sarcoma methyloma opens doors to new treatments
01.12.2016 | IDIBELL-Bellvitge Biomedical Research Institute

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>