(Press-News.org) 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
END
The following highlights summarize research papers that have been recently published in Geophysical Research Letters (GRL), Space Weather (SW), Journal of Geophysical Research-Earth Surface (JGR-F), and Journal of Geophysical Research-Biogeosciences, (JGR-G).
In this release:
Characterizing the Moon's radiation environment
Three-dimensional mapping of airflow over dunes
Forest organic runoff breaks down faster than agricultural, urban runoff
Examining CO2¬ concentrations and flow dynamics in streams
Measuring the forces generated by erosive debris flows
Agulhas ...
ATLANTA – A potential new strategy to developing new drugs to control inflammation without serious side effects has been found by Georgia State University researchers and international colleagues.
Jian-Dong Li, director of Georgia State's Center for Inflammation, Immunity and Infection, and his team discovered that blocking a certain pathway involved in the biological process of inflammation will suppress it.
Inhibiting a molecule called phosphodiesterase 4B, or PDE4B, suppresses inflammation by affecting a key gene called CLYD, a gene that serves as a brake on inflammation.
The ...
MADISON – The age at which a child with autism is diagnosed is related to the particular suite of behavioral symptoms he or she exhibits, new research from the University of Wisconsin–Madison shows.
Certain diagnostic features, including poor nonverbal communication and repetitive behaviors, were associated with earlier identification of an autism spectrum disorder, according to a study in the April issue of the Journal of the American Academy of Child and Adolescent Psychiatry. Displaying more behavioral features was also associated with earlier diagnosis.
"Early ...
PROVIDENCE, R.I. – A study at Rhode Island Hospital has found that despite complications, patients co-infected with the pandemic 2009-2010 influenza A H1N1 (pH1N1) and a second respiratory virus were not associated with worse outcomes or admission to the hospital's intensive care unit. The study is published online in the journal PLOS ONE.
"There is scant data in the literature regarding the incidence and impact of simultaneous infection by two respiratory viruses, particularly in adults," said senior investigator Leonard Mermel, D.O., medical director of the department ...
Multiple genes contribute to risk for schizophrenia and appear to function in pathways related to transmission of signals in the brain and immunity, according to an international study led by Virginia Commonwealth University School of Pharmacy researchers.
By better understanding the molecular and biological mechanisms involved with schizophrenia, scientists hope to use this new genetic information to one day develop and design drugs that are more efficacious and have fewer side effects.
In a study published online in the April issue of JAMA Psychiatry, the JAMA Network ...
A Johns Hopkins Children's Center survey of 102 clinicians who treat teenage girls with pelvic inflammatory disease (PID) has found that official guidelines designed to inform decisions about hospitalization versus outpatient care leave some clinicians scratching their heads.
The study, conducted by a team of adolescent medicine specialists and published online in the journal Sexually Transmitted Diseases, presented the clinicians with a series of common clinical scenarios and discovered a great deal of uncertainty among some trying to choose between inpatient and outpatient ...
SALT LAKE CITY, April 10, 2013 – University of Utah researchers developed a high-speed camera system that spent the past two winters photographing snowflakes in 3-D as they fell – and they don't look much like those perfect-but-rare snowflakes often seen in photos.
"Until our device, there was no good instrument for automatically photographing the shapes and sizes of snowflakes in free-fall," says Tim Garrett, an associate professor of atmospheric sciences. "We are photographing these snowflakes completely untouched by any device, as they exist naturally in the air."
Snowflakes ...
New research suggests that patients with knee osteoarthritis (OA) who wear flat, flexible footwear (mobility shoes) had significant reduction in knee loading—the force placed upon the joint during daily activities. Results published in Arthritis & Rheumatism, a journal of the American College of Rheumatology (ACR), show that long term use of the mobility shoes helped OA patients adapt their gait, or how they walk, which improved knee loading, even when the mobility shoes were no longer worn.
More than 27 million Americans over the age of 25 have some form of OA, which ...
Arizona workers' comp: health care workers suffer high injury rates
Article provided by Jerome, Gibson, Stewart, Stevenson, Engle & Runbeck, P.C.
Visit us at http://www.jeromegibsonlaw.com
It is no secret that health care settings can be dangerous places to work for doctors, nurses, aides and others. Duties involve heavy lifting, long periods of standing and walking, and frequent bending; exposure to contagious disease, infection, radiation and toxic substances; use of dangerous medical equipment like needles and syringes, and potential allergens like latex; ...
Options for separating couples who own a business interest in California
Article provided by The Bickerton Law Firm, APLC
Visit us at http://www.bickertonlaw.com
Dividing marital assets in a divorce is rarely easy. However, when married couples own an interest in a business, the complexity of property division may increase significantly. There are many options for dividing business interest that typically involve either some sort of buy-out or sale.
California is a community property state. That means that business interests acquired during the marriage are likely ...
