(Press-News.org) Contact information: Christine A. Somosi
christine.somosi@case.edu
216-368-6287
Case Western Reserve University
Researchers at Case Comprehensive Cancer Center discover ovarian cancer biomarker
MicroRNA predicts treatment response
Researchers at Case Western Reserve University have identified a microRNA biomarker that shows promise in predicting treatment response in the most common form of ovarian cancer – a breakthrough that has the potential to improve outcomes for patients with the disease.
A CWRU research team led by Analisa DiFeo, an assistant professor of General Medical Science-Oncology at the Case Comprehensive Cancer Center, found that the biomarker miR-181a is a molecular driver of epithelial ovarian cancer (EOC). The research team also found that elevated levels of miR-181a in ovarian tumors are associated with chemotherapy resistance and disease progression.
"By looking at the expression of this microRNA in tumor samples, we get an idea which women may respond to standard chemotherapy and which are at a high risk for recurrence," DiFeo said. "This helps guide treatment decisions and improve survival rates."
In the past, researchers have been unable to predict how EOC patients will respond to treatment. This marks the first time scientists have demonstrated that a single miRNA - miR-181a - increases the cellular survival, drug resistance and tumor metastasis of ovarian cancer cells by activating TGF-β, a potent cancer signaling pathway.
"Prognostic markers and early detection markers for ovarian cancer have been elusive," says Stanton Gerson, MD, Asa and Patricia Shiverick- Jane Shiverick (Tripp) Professor of Hematological Oncology, Director of the Case Comprehensive Cancer Center and Director of the Seidman Cancer Center at UH Case Medical Center. "This study is one of the first to indicate that, it is possible using a novel genomic analysis, to identify abnormalities specific to ovarian cancer. Women worldwide will benefit from this discovery."
Ninety percent of all women with ovarian cancer have the EOC subtype, which is the most lethal of all female reproductive track malignancies and the fifth- leading cause of cancer deaths in women worldwide. Each year, EOC claims an average of 15,000 lives and physicians diagnose 23,000 new cases. Because EOC is generally asymptomatic, most women are at an advance stage (Stage 3-4) by the time they are diagnosed. Approximately 70-80 percent% of patients who survive the disease after the first onset go on to face a recurrence.
DiFeo's findings, published in the January 7, 2014 issue of Nature Communications, provide new insights into the role of miRNAs as treatment biomarkers. MicroRNA like miR-181a – short, single stranded RNA molecules - fine tune the expression of as much as 60% of all protein encoding genes.
Through a collaboration with the Mount Sinai Medical Center in New York and the Mario Negri Institute of Pharmaceutical Research in Milan, Italy, DioFeo's team screened the expression of miRNA's in both primary and recurrent human ovarian tumors.
"We found that this (miR-181a) was one of the top expressing microRNAs in tumors from patients who recurred within the first six months after treatment," DiFeo said. "We also found higher levels in recurrent tumors compared to primary tumors in the women we tested."
A better understanding of the pathway that drives EOC will help researchers find potential therapeutic targets that could block the devastating effects of miR-181a, DiFeo adds. Her team discovered that miR-181a blocks the expression of the Smad7 gene, which generally shuts down the TGF-β signaling pathway, a potent inducer of metastases. When miR-181a blocks SMAD7, TGF-β works unabated and metastases occurs.
DiFeo, who began her research while at Mount Sinai Hospital in New York City, has been at CWRU Case Western Reserve since 2012. To determine patient response, her team analyzed 80 human tumor samples and used a combination of in vitro and preclinical ovarian mouse models (human tumor cells injected in a mouse) to access the function and pathway of miR-181a.
"We're now looking for small molecules that can block the interaction between miR-181a and Smad 7, stop TGF-β activation and prevent this micro-RNA from spreading and disseminating ovarian cancer," DiFeo said. Until this discovery is made, DiFeo suggests that doctors test for recurrence at more frequent intervals.
###
This work was supported by grants from the Department of Defense Ovarian Cancer Research Program CDMRP (W81XWH-11-1-0609) (A.D.) and Ovarian Cancer Research Fund Liz Tilberis Early Career Award (A.D.)
About Case Western Reserve University School of Medicine
Founded in 1843, Case Western Reserve University School of Medicine is the largest medical research institution in Ohio and is among the nation's top medical schools for research funding from the National Institutes of Health. The School of Medicine is recognized throughout the international medical community for outstanding achievements in teaching. The School's innovative and pioneering Western Reserve2 curriculum interweaves four themes--research and scholarship, clinical mastery, leadership, and civic professionalism--to prepare students for the practice of evidence-based medicine in the rapidly changing health care environment of the 21st century. Nine Nobel Laureates have been affiliated with the School of Medicine.
Annually, the School of Medicine trains more than 800 MD and MD/PhD students and ranks in the top 25 among U.S. research-oriented medical schools as designated by U.S. News & World Report's "Guide to Graduate Education."
The School of Medicine's primary affiliate is University Hospitals Case Medical Center and is additionally affiliated with MetroHealth Medical Center, the Louis Stokes Cleveland Department of Veterans Affairs Medical Center, and the Cleveland Clinic, with which it established the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University in 2002. http://casemed.case.edu
About Case Comprehensive Cancer Center
Case Comprehensive Cancer Center is an NCI-designated Comprehensive Cancer Center located at Case Western Reserve University. The center, now in its 25th year of funding, integrates the cancer research activities of the largest biomedical research and health care institutions in Ohio – Case Western Reserve, University Hospitals (UH) Case Medical Center and the Cleveland Clinic. NCI-designated cancer centers are characterized by scientific excellence and the capability to integrate a diversity of research approaches to focus on the problem of cancer. It is led by Stanton Gerson, MD, Asa and Patricia Shiverick- Jane Shiverick (Tripp) Professor of Hematological Oncology, director of the National Center for Regenerative Medicine, Case Western Reserve, and director of the Seidman Cancer Center at UH Case Medical Center.
Researchers at Case Comprehensive Cancer Center discover ovarian cancer biomarker
MicroRNA predicts treatment response
2014-01-08
ELSE PRESS RELEASES FROM THIS DATE:
Negative feedback makes cells 'sensitive'
2014-01-08
Negative feedback makes cells 'sensitive'
New research has shown that negative feedback loops in cell signalling systems can be essential for a cell's ability to perceive the strength of a growth stimulus. Cells lacking the feedback loop became insensitive ...
Heart attacks hit poor the hardest
2014-01-08
Heart attacks hit poor the hardest
Tel Aviv University researchers show that socioeconomic status is predictor of higher risk of disease and death after an attack
As people get older, their bodies wear down and become less resilient. In old age, it's ...
The ironic (and surprising) effects of weight stigma
2014-01-08
The ironic (and surprising) effects of weight stigma
UCSB psychology professor finds that messages designed to encourage weight loss may actually have the opposite effect
(Santa Barbara, Calif.) — If you're one of the millions of people who ...
Penn biologists establish new method for studying RNA's regulatory 'footprint'
2014-01-08
Penn biologists establish new method for studying RNA's regulatory 'footprint'
Increasingly, biologists have come to realize that RNA is not merely a transitional state between DNA and proteins but plays a major role in determining whether and how genes ...
Scripps Florida scientists identify possible key to drug resistance in Crohn's disease
2014-01-08
Scripps Florida scientists identify possible key to drug resistance in Crohn's disease
JUPITER, FL, January 7, 2014 – Two-thirds to three-quarters of the estimated 700,000 Americans living with Crohn's disease, an autoimmune condition that can disrupt the entire ...
Massive exoplanets may be more Earth-like than thought
2014-01-08
Massive exoplanets may be more Earth-like than thought
'Super-Earths' likely to have both oceans and continents
Massive terrestrial planets, called "super-Earths," are known to be common in our galaxy, the Milky Way. Now a Northwestern University astrophysicist ...
Many small exoplanets found to be covered in gas
2014-01-08
Many small exoplanets found to be covered in gas
New measurements of mass expand knowledge of exoplanets' compositions
During its four-year mission, NASA's Kepler space telescope discovered thousands of "planetary candidates" in our Milky Way galaxy -- the vast ...
Sugar-sweetened beverage tax could reduce obesity and type 2 diabetes in India
2014-01-08
Sugar-sweetened beverage tax could reduce obesity and type 2 diabetes in India
A sugar-sweetened beverage (SSB) tax could help mitigate the rise in obesity and type 2 diabetes rates in India among both urban and rural populations, according to a study published this week ...
Link found between intimate partner violence and termination of pregnancy
2014-01-08
Link found between intimate partner violence and termination of pregnancy
Intimate partner violence in women (sometimes referred to as domestic violence) is linked to termination of pregnancy, according to a study by UK researchers published in this week's PLOS Medicine. ...
50 years of tobacco control significantly extended lives of 8 million Americans
2014-01-08
50 years of tobacco control significantly extended lives of 8 million Americans
Former smoker John Hilburn says a cigarette warning label and costs prompted him to kick the habit 30 years ago
WASHINGTON — The Surgeon General's report of 1964 which outlined, for the ...
LAST 30 PRESS RELEASES:
Youngest in class at higher risk of mental health problems
American Heart Association announces new volunteer leaders for 2025-26
Gut microbiota analysis can help catch gestational diabetes
FAU’s Paulina DeVito awarded prestigious NSF Graduate Research Fellowship
Champions for change – Paid time off initiative just made clinical trials participation easier
Fentanyl detection through packaging
Prof. Eran Meshorer elected to EMBO for pioneering work in epigenetics
New 3D glacier visualizations provide insights into a hotter Earth
Creativity across disciplines
Consequences of low Antarctic sea ice
Hear here: How loudness and acoustic cues help us judge where a speaker is facing
A unique method of rare-earth recycling can strengthen the raw material independence of Europe and America
Epilepsy self-management program shows promise to control seizures, improve mood and quality of life
Fat may play an important role in brain metabolism
New study finds no lasting impact of pandemic pet ownership on human well-being
New insights on genetic damage of some chemotherapies could guide future treatments with less harmful side effects
Gut microbes could protect us from toxic ‘forever chemicals’
Novel modelling links sea ice loss to Antarctic ice shelf calving events
Scientists can tell how fast you're aging from a single brain scan
U.S. uterine cancer incidence and mortality rates expected to significantly increase by 2050
Public take the lead in discovery of new exploding star
What are they vaping? Study reveals alarming surge in adolescent vaping of THC, CBD, and synthetic cannabinoids
ECMWF - delivering forecasts over 10 times faster and cutting energy usage by 1000
Brazilian neuroscientist reveals how viral infections transform the brain through microscopic detective work
Turning social fragmentation into action through discovering relatedness
Cheese may really be giving you nightmares, scientists find
Study reveals most common medical emergencies in schools
Breathable yet protective: Next-gen medical textiles with micro/nano networks
Frequency-engineered MXene supercapacitors enable efficient pulse charging in TENG–SC hybrid systems
Developed an AI-based classification system for facial pigmented lesions
[Press-News.org] Researchers at Case Comprehensive Cancer Center discover ovarian cancer biomarkerMicroRNA predicts treatment response