(Press-News.org) La Jolla, Calif., April 20, 2015 - A new research study has shown that pancreatic cancer cells can be coaxed to revert back toward normal cells by introducing a protein called E47. E47 binds to specific DNA sequences and controls genes involved in growth and differentiation. The research provides hope for a new treatment approach for the more than 40,000 people who die from the disease each year in the United States.
"For the first time, we have shown that overexpression of a single gene can reduce the tumor-promoting potential of pancreatic adenocarcinoma cells and reprogram them toward their original cell type. Thus, pancreatic cancer cells retain a genetic memory which we hope to exploit," said Pamela Itkin-Ansari, Ph.D., adjunct professor in the Development, Aging, and Regeneration Program at Sanford-Burnham and lead author of the study published today in the journal Pancreas.
E47 turns the clock back
The study, a collaborative effort between Sanford-Burnham, UC San Diego, where Itkin-Ansari holds a joint appointment, and Purdue University, generated human pancreatic ductal adenocarcinoma cell lines to make higher than normal levels of E47. The increased amount of E47 caused cells to stall in the G0/G1 growth phase, and differentiate back toward an acinar cell phenotype.
In vivo studies showed that when the reprogrammed cancer cells were introduced into mice, their ability to form tumors was greatly diminished compared to untreated adenocarcinoma cells.
"Presently, pancreatic adenocarcinoma is treated with cytotoxic agents, yet the average survival for patients post-diagnosis is merely six months, and the improvements in therapies are measured in days," said Andrew M. Lowy, M.D., professor of surgery at the UC San Diego Moores Cancer Center and co-chair of the National Cancer Institute's Pancreatic Cancer Task Force. "The finding that we can differentiate these cancer cells back to a non-threatening phenotype is encouraging. Indeed, there is a precedent for cell differentiation therapy in that the approach has been used to treat acute promyelocytic leukemia (APL) and some neuroblastomas successfully."
"Our next step is to test primary patient-derived tumor tissue to determine whether E47 can produce similar results, potentially providing a novel therapeutic approach to combat this highly lethal disease," said Itkin-Ansari. "Additionally, we are screening for molecules--potential drugs--that can induce overexpression of E47."
Pancreatic adenocarcinoma
Pancreatic adenocarcinoma is the most common form of pancreatic cancer. It's primarily caused by a mutation in the oncogene called Kras that causes the digestive enzyme-secreting cells (acinar cells) to differentiate into a destabilized duct-like cell type, which is cancerous. The disease is often called a "silent" cancer because it rarely shows early symptoms--it tends to be diagnosed at advanced stages when it causes weight loss, abdominal pain, and jaundice.
INFORMATION:
The study was funded by support from the Hartwell Foundation, The Hisrshberg Foundation, by the NCI under award number 5P30CA030199, by the NIH under award numbers DK55489 and CA124586, by the National Research Foundation of Korea award number 2011-0013127, and Yonsei University College of Medicine for 2012 (6-2012-0078)
ABOUT SANFORD-BURNHAM MEDICAL RESEARCH INSTITUTE
Sanford-Burnham Medical Research Institute is dedicated to discovering the fundamental molecular causes of disease and devising the innovative therapies of tomorrow. Sanford-Burnham takes a collaborative approach to medical research with major programs in cancer, neurodegeneration and stem cells, diabetes, and infectious, inflammatory, and childhood diseases. The Institute is recognized for its National Cancer Institute-designated Cancer Center, its NIH-designated Neuroscience Center Cores, and expertise in drug discovery technologies. Sanford-Burnham is a nonprofit, independent institute that employs more than 1,000 scientists and staff in San Diego (La Jolla), Calif., and Orlando (Lake Nona), Fla. For more information, visit us at sanfordburnham.org.
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COLUMBUS, Ohio--As new medical diagnostics become available, researchers are increasingly discovering situations in which pets can transmit diseases to humans--especially when an owner's immune system is compromised.
At The Ohio State University and partner institutions, researchers have compiled the latest information from more than 500 studies worldwide to make recommendations on how families can minimize the risk of disease transmission by choosing the right type of pet, or by making small changes in how they enjoy the pets they already have.
The review was published ...
A new diagnostic method, namely spectral histopathology, facilitates marker-free detection of individual subtypes of lung cancers. It was developed by researchers at the PURE consortium at Ruhr-Universität Bochum (RUB). They have successfully applied it in collaboration with clinicians at the Ruhrlandklinik in Essen. It is an automatable imaging process which, by classifying specific forms of lung cancer, facilitates a prognosis regarding a tumour's aggressiveness. The team, headed by RUB Prof Dr Klaus Gerwert, compares the results of traditional diagnostic procedures ...
CLEMSON, S.C. -- In a groundbreaking achievement led by an international team that includes Clemson scientist Chris Saski, the intricately woven genetic makeup of Upland cotton has been decoded for the first time in the ancient plant's history.
Saski participated in sequencing the genome, which is a crucial stepping-stone toward further advancements of understanding the inner workings of one of the most complex and treasured plants on the planet.
The future implications of Saski's research in the short and long terms are both financial and holistic. Upland cotton, which ...
CORVALLIS, Ore. - Researchers at Oregon State University have invented a new technology that can increase the bandwidth of WiFi systems by 10 times, using LED lights to transmit information.
The technology could be integrated with existing WiFi systems to reduce bandwidth problems in crowded locations, such as airport terminals or coffee shops, and in homes where several people have multiple WiFi devices.
Experts say that recent advances in LED technology have made it possible to modulate the LED light more rapidly, opening the possibility of using light for wireless ...
NEW YORK (April 20, 2015) -- Genomic studies have illuminated the ways in which malfunctioning genes can drive cancer growth while stunting the therapeutic effects of chemotherapy and other treatments. But new findings from Weill Cornell Medical College investigators indicate that these genes are only partly to blame for why treatment that was at one point effective ultimately fails for about 40 percent of patients diagnosed with the most common form of non-Hodgkin Lymphoma.
The study, published April 20 in Nature Communications, suggests that global changes in cancer ...
A rigorous analysis of antimalarial drug quality conducted in Cambodia and Tanzania found no evidence of fake medicines, according to new research published in the American Journal of Tropical Medicine and Hygiene.
But researchers warn that routine surveillance is crucial as poor quality medicines exist, leaving malaria patients at risk of dying and increasing the risk of drug resistance.
Previous reports had suggested that up to one third of antimalarials could be fake. Researchers from the Artemisinin-based Combination Therapy (ACT) Consortium at the London School ...
Dispensing of prescription opioid pain relievers and prescription opioid overdoses both dropped substantially after abuse-deterrent extended-release oxycodone hydrochloride was introduced on the pharmaceutical market and the narcotic drug propoxyphene was withdrawn from the U.S. market in 2010, according to an article published online by JAMA Internal Medicine.
The abuse-deterrent OxyContin formulation is resistant to crushing and dissolving, actions that have been used to bypass the extended-release mechanism to get a quicker and more intense high. Propoxyphene (also ...
Children whose families and pediatricians were most faithful to an obesity intervention program that included computerized clinical decision support for physicians and health coaching for families experienced the greatest improvements in body mass index (BMI), according to an article published online by JAMA Pediatrics.
The prevalence of childhood obesity in the United States remains at historically high levels. Clinical approaches that are cost-effective and scalable for obesity reduction in children are a public health priority. However, interventions to improve BMI ...
(Boston) - Results of a new study led by Boston Medical Center (BMC) researchers, in collaboration with Harvard Medical School (HMS), indicate that the introduction of abuse-deterrent OxyContin, coupled with the removal of propoxyphene from the US prescription marketplace, may have played a role in decreasing opioid prescribing and overdoses. The findings, published in JAMA Internal Medicine, showed that these two changes led to a 19 percent drop in prescription opioid supply that was mirrored by a 20 percent drop in prescription opioid overdose between August 2010 and ...
Poor quality medicines are a real and urgent threat that could undermine decades of successful efforts to combat HIV/AIDS, malaria and tuberculosis, according to the editors of a collection of journal articles published today. Scientists report up to 41 percent of specimens failed to meet quality standards in global studies of about 17,000 drug samples. Among the collection is an article describing the discovery of falsified and substandard malaria drugs that caused an estimated 122,350 deaths in African children in 2013. Other studies identified poor quality antibiotics, ...
