PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

Mouse model improves understanding of clear cell sarcoma

Nobel Laureate Mario R. Capecchi leads collaboration of researchers

2013-02-11
(Press-News.org) (SALT LAKE CITY)—Geneticists led by University of Utah Nobel Prize Laureate Mario R. Capecchi, Ph.D., have engineered mice that develop clear cell sarcoma (CCS), a significant step in better understanding how this rare and deadly soft tissue cancer arises. The mouse model also can potentially speed the development of drugs to target genes that must be activated for the cancer to form.

CCS arises in connective soft tissues, such as tendons, fat, blood vessels, and muscle. Researchers have known that the first step in the process that leads to CCS occurs when two human chromosomes, 12 and 22, randomly break after DNA gets damaged from the effects of sunlight or other causes. Each chromosome usually harmlessly rejoins after breaking. But occasionally part of one chromosome will join with part of the other to create a new gene called a fusion gene. When this gene, ews-atf1 is generated, it initiates the process that causes CCS.

The rare and aggressive nature of sarcomas, and their occurrence in children and young adults, long has interested Capecchi. In a study in the Feb. 11, 2013, online edition of Cancer Cell, he and colleagues from the University of Utah, the University of Texas M.D. Anderson Cancer Center in Houston, and Stanford University, describe how they developed the first mouse model of CCS by essentially recreating the human ews-atf1 gene in mice.

Capecchi, distinguished professor of human genetics and a Howard Hughes Medical Institute Investigator, says having a mouse model will teach researchers not only about CCS but also might provide an avenue for developing a drug that is more successful than current therapies. "Now that we have a mouse model for CCS, we can investigate what other events or gene mutations are required to form tumors," he says. "It also gives us the opportunity to investigate whether the CCS fusion gene might be a specific target for drugs."

Sarcomas often are removed by surgery, which is followed by radiation or chemotherapy. If the fusion gene turns out to be a viable drug target, Capecchi cautions, it could take a decade or longer before it's available to those with the disease.

Information from the National Cancer Institute estimated that 11,280 U.S. residents would be diagnosed with the disease in 2012, with approximately 3,900 people expected to die. Estimated mortality rates of CCS vary, but it is considered an aggressive cancer, with a five-year mortality rate of approximately 80 percent. In the United States, CCS accounts for around 7 percent of cancers among children, adolescents, and young adults under age 20, according to the National Cancer Institute.

To make the mouse model of CCS, Capecchi and his colleagues had to create the ews-atf1 fusion gene in mice. For this they employed the technique he developed and in 2007 was awarded the Nobel Prize in physiology or medicine for: gene targeting.

They manipulated the process by which a gene found in every mouse cell, rosa26, receives the instructions that determine its function. Called transcription, this process, is initiated by a region of DNA, known as a promoter, on the same chromosome as rosa26. Capecchi and his team used a molecular agent to interrupt the transcription process and induce the promoter to instead make the fusion gene on command of the enzyme that activates it. To turn on the fusion gene, this enzyme, Cre, also must be activated, and to do that the researchers used tamoxifen—the same molecule in cancer drugs. To introduce Cre into cells, Capecchi used a small sequence of HIV as a vehicle for the enzyme to enter mouse cells that contained the fusion gene.

Although different cell types could give rise to this cancer, Capecchi identified mesenchymal stem cells, which can create a large number of tissue types, including the soft tissue where sarcomas form, as being especially good for producing CCS tumors. To activate the fusion gene, Cre must be injected into a mouse after birth.

Along with opening new avenues to understand and potentially treat CCS, the new mouse model also can help researchers learn more about carcinomas, the more common forms of human cancer, Capecchi believes. Carcinomas occur in the tissue that forms the inner and outer surfaces of organs, glands, and body cavities. These types of cancers require multiple steps and take a long time to develop, making them more difficult to study.

"My feeling is that identifying the different steps that give rise to CCS tumors may be informative on how carcinomas develop." Capecchi says. "Sarcomas are genetically more stable than carcinomas, which makes it easier to identify the events leading to the cancer. Learning about CCS might shed light on carcinomas."

There are more than 20 types of sarcoma, each with a different fusion gene, according to Capecchi.

### The first author on the study is Krystal M. Straessler, a graduate student in Capecchi's lab. The other authors are Kevin B. Jones, M.D., and Huifeng Jin, both of the University of Utah orthopedics department and Hunstman Cancer Institute Center for Children's Cancer; Hao Hu, University of Texas M.D. Anderson Cancer Center, Houston; Matt van de Rijn, Stanford University Medical Center, Palo Alto, Calif.


ELSE PRESS RELEASES FROM THIS DATE:

Researchers identify genetic root to early-onset prostate cancer

2013-02-11
Prostate cancer is often considered an elderly man's disease, and little is known about the approximately 2% of cases that arise in men who are aged 50 years or younger. Research published in the February 11th issue of the Cell Press journal Cancer Cell uncovers the genetic origin of such early-onset prostate cancer. The findings could help in the development of new diagnostic, prognostic, therapeutic, and prevention strategies for the disease. "It's been unclear whether prostate cancer in the young is explainable by a different mechanism than prostate cancer in the elderly. ...

International study suggests improved treatment alternative for lymphoid leukemia

2013-02-11
CINCINNATI – Discovering what they call the "Achilles' heel" for lymphoid leukemia, an international research team has tested a possible alternative treatment that eradicated the disease in mouse models. Reporting their results Feb. 11 in the journal Cancer Cell, the scientists said the targeted molecular therapy described in their study could have direct implications for current treatment of Acute Lymphoid Leukemia (ALL) in people. Led by researchers at Cincinnati Children's Hospital Medical Center and the Institut de recherches cliniques de Montreal (ICRM), the study ...

Study finds difficulty obtaining pricing, varying costs for total hip replacement

2013-02-11
Researchers who sought to determine whether pricing information for a total hip replacement could be obtained from hospitals and physicians found getting such information was often difficult and that there were wide variations in the quoted prices, according to a report published Online First by JAMA Internal Medicine, a JAMA Network publication. Data on hospital quality – and to a lesser degree physician quality – are available from public and private sector sources. However, data on hospital and physician pricing are more difficult to obtain, the authors write in the ...

Tumor blood vessels prevent the spread of cancer cells

2013-02-11
A lack of the protein endoglin in the blood vessels of tumour-bearing mice enables the spread of daughter tumours, according to researchers at Karolinska Institutet and Lund University in Sweden in a study published in the scientific periodical The Journal of Experimental Medicine. Given that the tumour vasculature constitutes an important barrier to the spread of cancer cells, the team suggests that drugs should be developed to strengthen the blood vessels' protective function. Studies of the process of metastasis (the spread of daughter tumours) have mainly focused ...

Earth-directed CME released by long duration solar flare

Earth-directed CME released by long duration solar flare
2013-02-11
On Feb. 9, 2013 at 2:30 a.m. EST, the sun erupted with an Earth-directed coronal mass ejection or CME, associated with a long duration C2.4-class flare. Experimental NASA research models, based on observations from the Solar Terrestrial Relations Observatory (STEREO) and ESA/NASA's Solar and Heliospheric Observatory, show that the CME left the sun at speeds of around 500 miles per second, which is a fairly typical speed for CMEs. Historically, CMEs at this speed are usually benign. Not to be confused with a solar flare, a CME is a solar phenomenon that can send solar ...

CWRU study suggests interacting with avatars may reduce depressive symptoms in young adults

2013-02-11
Young adults, in a period of transition, are often reluctant to seek treatment for mental health problems because of the stigma, inadequate insurance coverage and difficulty finding a mental health care provider. But a new preliminary study by researchers at Case Western Reserve University suggests that depression symptoms may be significantly reduced when 18- to 25-year-olds interact with computerized avatars—virtual 3D images of a healthcare provider like a nurse practitioner or physician —as a way to rehearse office visits ahead of time and learn self-management skills. ...

Researchers find Asian needle ants displacing other aggressive invaders

Researchers find Asian needle ants displacing other aggressive invaders
2013-02-11
Researchers from North Carolina State University have found that one of the most aggressive invasive ant species in the United States – the Argentine ant – appears to have met its match in the Asian needle ant. Specifically, the researchers have found that the Asian needle ant is successfully displacing Argentine ants in an urban environment, indicating that the Asian needle ant – with its venomous sting – may be the next invasive species to see a population boom. In the world of invasive species, the Argentine ant (Linepithema humile) is a success story. Its aggressive, ...

Online or off, bullying proves harmful

Online or off, bullying proves harmful
2013-02-11
EAST LANSING, Mich. — Children who are bullied online or by mobile phone are just as likely to skip school or consider suicide as kids who are physically bullied, according to a study led by a Michigan State University criminologist. The findings, published in the International Criminal Justice Review, suggest parents, school officials and policymakers should consider bullying experiences both on and offline when creating anti-bullying policies and procedures. "We should not ignore one form of bullying for the sake of the other," said Thomas Holt, associate professor ...

Study shows progesterone shots do not reduce preterm delivery in twin pregnancies

2013-02-11
In a study to be presented on February 14 between 8 a.m. and 10 a.m. PST, at the Society for Maternal-Fetal Medicine's 33rd annual meeting, The Pregnancy Meeting ™, researchers will report findings that suggest that 17P, a form of progesterone, is not effective in preventing preterm birth among women with twin pregnancies — and may possibly be harmful. While 17P (17 alpha-hydroxyprogesterone caproate) has been shown to prevent premature delivery among about one-third of women with a singleton pregnancy who have experienced a prior preterm delivery, this latest research ...

Rice University lab shows how blood vessels regroup after stroke

2013-02-11
By thinking of cells as programmable robots, researchers at Rice University hope to someday direct how they grow into the tiny blood vessels that feed the brain and help people regain functions lost to stroke and disease. Rice bioengineer Amina Qutub and her colleagues simulate patterns of microvasculature cell growth and compare the results with real networks grown in their lab. Eventually, they want to develop the ability to control the way these networks develop. The results of a long study are the focus of a new paper in the Journal of Theoretical Biology. "We ...

LAST 30 PRESS RELEASES:

Menopause drug reduces hot flashes by more than 70%, international clinical trial finds

FGF21 muscle hormone associated with slow ALS progression and extended survival

Hitting the right note: The healing power of music therapy in the cardiac ICU

Cardiovascular disease risk rises in Mexico, despite improved cholesterol control

Flexible optical touch sensor simultaneously pinpoints pressure strength and location

Achalasia diagnosis simplified to AI plus X-ray

PolyU scholars pioneer smart and sustainable personal cooling technologies to address global extreme heat

NIH grant aims for childhood vaccine against HIV

Menstrual cycle and long COVID: A relation confirmed

WMO report on global water resources: 2024 was characterized by both extreme drought and intense rainfall

New findings explain how a mutation in a cancer-related gen causes pulmonary fibrosis

Thermal trigger

SNU materials science and engineering team identifies reconstruction mechanism of copper alloy catalysts for CO₂ conversion

New book challenges misconceptions about evolution and our place in the tree of life

Decoding a decade of grouper grunts unlocks spawning secrets, shifts

Smart robots revolutionize structural health monitoring

Serum-derived hsa_circ_101555 as a diagnostic biomarker in non-hepatocellular carcinoma chronic liver disease

Korea University study identifies age 70 as cutoff for chemotherapy benefit in colorectal cancer

Study explores brain cell communication called ‘crosstalk’

4 beer and wine discoveries

Massage Therapy Foundation awards $299,465 research grant to Children’s Hospital of Philadelphia

Chung-Ang University develops chloride-resistant Ru nanocatalysts for sustainable hydrogen production from seawater

Afghanistan’s August 2025 earthquake reveals the cost of international isolation, UN scientists warn

Shortlist announced for Panmure House Prize

Small nuclear RNA base editing a safer alternative to CRISPR, UC San Diego researchers find

Can Hayabusa2 touchdown? New study reveals space mission’s target asteroid is tinier and faster than thought

Millisecond windows of time may be key to how we hear, study finds

Graz University of Technology opens up new avenues in lung cancer research with digital cell twin

Exoplanets are not water worlds

Study shows increasing ‘healthy competition’ between menu options nudges patients towards greener, lower-fat hospital food choices

[Press-News.org] Mouse model improves understanding of clear cell sarcoma
Nobel Laureate Mario R. Capecchi leads collaboration of researchers