Breaking News
January 23, 2019 - Medical expert advises people with epilepsy not to stockpile medicines
January 23, 2019 - Bedfont to exhibit NObreath FeNO monitor at Arab Health 2019
January 23, 2019 - Nicotinamide riboside supplementation confers significant physiological benefits to mothers and offspring
January 23, 2019 - Increasing temperatures may help preserve crop nutrition
January 23, 2019 - Many Oncologists in the Dark About LGBTQ Health Needs
January 23, 2019 - Epigenetic change causes fruit fly babies to inherit diet-induced heart disease
January 23, 2019 - Erasing memories could reduce relapse rates among drug addicts
January 23, 2019 - African Americans who smoke cigarettes are more likely to develop peripheral artery disease
January 23, 2019 - Unique data combination helps FinnGen researchers to fund links between genetic factors and health
January 23, 2019 - Parents’ mental health problems associated with reactive attachment disorder in children
January 23, 2019 - Graphene Flagship project studies impact of graphene and related materials on our health
January 23, 2019 - The connection between the Pope and contraceptive pills
January 23, 2019 - Prior dengue infection could protect children from symptomatic Zika
January 23, 2019 - VISTA checkpoint implicated in pancreatic cancer immunotherapy resistance
January 23, 2019 - The Tiny Camera That Could Revolutionize Cardiovascular Surgery
January 23, 2019 - Peptide isolated from soil fungi has antitumor and antibacterial properties
January 23, 2019 - TGen identifies polio-like virus as potential cause of Acute Flaccid Myelitis outbreak
January 23, 2019 - Migrants and refugees do not bring disease and are at greater health risk themselves says WHO
January 23, 2019 - Examing the effects of menopause in workplace
January 23, 2019 - Enemy number 1 – Air pollution and climate change top of WHO agenda
January 23, 2019 - Two Positive Phase III studies of Tafenoquine for the Radical Cure of Plasmodium vivax Malaria Published in The New England Journal of Medicine
January 23, 2019 - World Trade Center responders at increased risk for head and neck cancers
January 23, 2019 - Low-sugar diet leads to significant improvement in nonalcoholic fatty liver disease in boys
January 23, 2019 - Chaos in bodily regulation can optimize our immune system, finds study
January 23, 2019 - Short, text-based exercises can increase happiness for adults recovering from substance use disorders
January 23, 2019 - Body size may have greater influence on women’s lifespan than men
January 23, 2019 - Groundbreaking tool helps visualize neuronal activity with near-infrared light
January 23, 2019 - Prior dengue immunity in children may be protective against symptomatic Zika
January 23, 2019 - Holocaust survivors with PTSD and their offspring exhibit more unhealthy behavior patterns
January 23, 2019 - Scientists discover new genetic mutations causing inherited deaf-blindness
January 23, 2019 - UC team designs new naloxone-dispensing smart device
January 23, 2019 - Torrent Pharmaceuticals Limited Issues Voluntary Nationwide Recall of Losartan Potassium Tablets, USP and Losartan Potassium and Hydrochlorothiazide Tablets, USP
January 23, 2019 - Brain activity shows development of visual sensitivity in autism
January 23, 2019 - Two hour gap between dinner and sleep is overrated says Japanese research
January 23, 2019 - Fear and embarrassment are causing smear test numbers to plummet
January 23, 2019 - Protein-secreting device implanted in epileptic rats reduces seizures, improves cognition
January 23, 2019 - Reintroduction project recovers current wild population of green turtle in Cayman Islands
January 23, 2019 - Cancer survivors face greater financial burden related to medical bills
January 23, 2019 - PSA screening reduces prostate cancer deaths by 30%
January 23, 2019 - LSTM receives grant to help improve health of people living in informal settlements
January 23, 2019 - Hemochromatosis Mutation Linked to Other Morbidity
January 23, 2019 - Why early diagnosis of autism should lead to early intervention
January 23, 2019 - Aspirin May Lower Stroke Risk in Women with History of Preeclampsia
January 23, 2019 - Exposure to certain chemicals may be linked to decrease in blood pressure during pregnancy
January 23, 2019 - Bowel cancer on the rise among younger Australians
January 23, 2019 - Scientists have reversed memory loss in a mouse model of Alzheimer’s
January 23, 2019 - Defective molecular master switch could lead to age-related macular degeneration
January 23, 2019 - Researchers identify how concussions may contribute to seizures
January 23, 2019 - Short interval between last meal of the day and bedtime may not affect blood glucose levels
January 23, 2019 - Still Too Many Highway Deaths Tied to Speeding
January 23, 2019 - Prenatal valproate exposure linked to increased ADHD risk
January 23, 2019 - Compound identified that may help treat heart failure
January 23, 2019 - Undiagnosed Asthma in Urban Adolescents May Be Common
January 23, 2019 - Study describes metabolism of intestinal microbiota in babies for the first time
January 22, 2019 - Study links concussions to development of epilepsy
January 22, 2019 - Specialist-led hospital bereavement service may help restrain legal action after difficult deaths
January 22, 2019 - Genetic study reveals possible new routes to treating osteoarthritis
January 22, 2019 - Blood test may detect early signs of lung-transplant rejection
January 22, 2019 - Blood marker could aid in early prediction of Alzheimer’s progression
January 22, 2019 - Orthodontic treatment does not guarantee future dental health
January 22, 2019 - Rutgers researchers discover cause of bone loss in people with joint replacements
January 22, 2019 - Diversity among rural Africans extends to their gut microbiomes
January 22, 2019 - Newly developed biological system lets cells to create self-curving cornea
January 22, 2019 - VTv Therapeutics Announces Publication of Comprehensive Data in Science Translational Medicine Detailing the Discovery and Clinical Development of TTP399, including Results of Phase 2 AGATA Study
January 22, 2019 - about one in three adults with prediabetes has arthritis
January 22, 2019 - A look at how data is democratizing health care
January 22, 2019 - Alcohol-Linked Disease Overtakes Hep C As Top Reason For Liver Transplant
January 22, 2019 - Researchers identify new genes linked with age-related macular degeneration
January 22, 2019 - MPFI researchers identify synaptic logic for connections between two brain hemispheres
January 22, 2019 - New approach to reduce toxic protein production in ALS
January 22, 2019 - New study extends our knowledge of the link between miRNAs and cancer
January 22, 2019 - Asthma, eczema are not barriers to active lifestyle in teenagers
January 22, 2019 - Genetic changes may predict likelihood of relapse in breast cancer patients
January 22, 2019 - Antiepileptic drug use by people with Alzheimer’s disease linked to accumulation of hospital days
January 22, 2019 - IUPUI researcher receives $2.85 million grant to find ways to improve bone strength
January 22, 2019 - Precision medicine can help keep astronauts healthy during deep space missions
January 22, 2019 - Detecting signs of neurodegeneration earlier and more accurately
January 22, 2019 - Mouse studies challenge ‘inhibition’ theory of autism
January 22, 2019 - SSB launches BIOSTAT RM TX single-use bioreactor for producing consistent quality cellular products
January 22, 2019 - Experimental drug can positively modify key characteristic behavior in FXS patients
Researchers develop promising targeted strategy to treat chemo-resistant blood cancer

Researchers develop promising targeted strategy to treat chemo-resistant blood cancer

image_pdfDownload PDFimage_print

Researchers from The Ottawa Hospital and the University of Ottawa have developed a promising targeted strategy to treat chemotherapy-resistant acute myeloid leukemia (AML) and a diagnostic test to determine which AML patients would most likely benefit from this treatment. In a mouse model, the experimental treatment eliminated all signs of disease (complete remission) in 100 percent of animals, while those that received the standard treatment all died. The results are published in the leading cancer journal Cancer Discovery.

“We were blown away when we saw the results,” said senior author Dr. William Stanford, a senior scientist at The Ottawa Hospital and professor at the University of Ottawa. “If these findings hold up in clinical trials, we could have a new treatment for people who would almost certainly die of their disease today.”

AML is the most common type of leukemia in adults, killing more than 10,000 people each year in Canada and the U.S. It starts in blood stem cells found in the bone marrow. Chemotherapy has been the first-line treatment for more than 40 years. However, about a third of people do not respond initially, and another 40 to 50 percent relapse (their cancer comes back) after an initial response. Most of these people eventually die of their disease.

Dr. Stanford’s research focuses on a protein called MTF2, which places chemical tags near certain genes to help control their expression (called epigenetics). Dr. Stanford previously found that MTF2 plays a role in blood development. He then teamed up with Dr. Mitchell Sabloff, a hematologist at The Ottawa Hospital, to see if it also plays a role in blood cancer.

Using AML samples from patients treated at The Ottawa Hospital, the team found that people with normal MTF2 activity were three times more likely to be alive five years after their initial chemotherapy treatment than people with low MTF2 activity.

“Initially we thought that MTF2 could be an important biomarker to identify patients who might benefit from experimental therapies,” said Dr. Stanford. “But then we started thinking that if we could understand what MTF2 was doing, maybe we could use this information to develop a new treatment.”

Dr. Stanford and his colleagues then discovered that MTF2 helps to place a chemical tag near a gene called MDM2, which is known to help cells resist chemotherapy. In AML cells with normal MTF2, this tag lowers MDM2 levels and ensures that cells die when they are damaged by chemotherapy. On the other hand, AML cells with low MTF2 can’t put tags on MDM2 to decrease its expression. These cells keep on living and dividing even when exposed to high levels of chemotherapy.

Since drugs that block or inhibit MDM2 are already being tested in clinical trials for other types of cancer, the team tested these in mouse models of AML using cells derived from patients whose cancer was resistant to chemotherapy. Mice treated with the MDM2 inhibitors plus chemotherapy all survived until the experiment ended four months later, and had no evidence of cancer, while those treated with chemotherapy alone all died.

“The preclinical animal data is very encouraging,” said Dr. Caryn Ito, a senior investigator at The Ottawa Hospital who developed the mouse models and co-led the study. “Our dedicated team of basic and clinical researchers worked extremely hard on this project. We were totally surprised by the findings, which we hope to translate to the clinic soon.”

The researchers are now trying to obtain pharmaceutical-grade MDM2 inhibitors to conduct trials in people with AML at The Ottawa Hospital. They are also screening libraries of approved drugs to see if any of these can block MDM2. And they are working with a biotech company to develop a test to identify chemotherapy-resistant AML patients, who would respond to these kinds of drugs. They have also filed a patent related to their discovery.

“We still have a lot of research to do, but if this works it could make a difference for patients around the world,” said Dr. Sabloff, who is also an associate professor at the University of Ottawa, Director of The Ottawa Hospital’s Leukemia Program and the Co-Director of the hematology bio-bank at the hospital. “I want to thank the many patients at The Ottawa Hospital who have and continue to generously donate blood and bone marrow for this research.”

Source:

http://www.ohri.ca/newsroom/story/view/1054?l=en

Tagged with:

About author

Related Articles