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

Study: Metformin for breast cancer less effective at higher glucose concentrations

2013-10-24
(Press-News.org) Contact information: Garth Sundem
garth.sundem@ucdenver.edu
University of Colorado Denver
Study: Metformin for breast cancer less effective at higher glucose concentrations A University of Colorado Cancer Center study published online this month in the journal Cell Cycle shows that breast cancer cell growth, motility and aggression is promoted by excess glucose, as experienced by patients with diabetes and metabolic syndrome. The study also showed that patients with high glucose may require higher doses of the drug metformin to achieve the same anti-cancer activity as patients with normal glucose levels.

Metformin, the most common first-line drug in the treatment of type-2 diabetes, has been shown in previous studies to reduce breast cancer risk, improve survival, and increase the effectiveness of chemotherapy. Numerous Phase III clinical trials are currently evaluating the benefits and best uses of metformin in breast cancer patients.

"We show that metformin works differently in high- compared to low-glucose conditions. Not only does it require a higher concentration of metformin to be active in high-glucose conditions, but we report that the drug regulates different genes within cancer cells at high as compared to normal glucose levels," says Ann Thor, MD, CU Cancer Center investigator, Todd Professor of Pathology at the University of Colorado School of Medicine, and the study's principal investigator.

The study evaluated the effects of metformin on 17 breast cancer cell lines representing each of the molecular subtypes of the disease, at varying glucose levels. "Commonly, lab studies of metformin are performed with very high glucose concentrations – about 17 millimols of glucose per liter. But the average glucose level in healthy humans is only about one third of that dose – about 5 millimols per liter. And individuals with diabetes may have glucose at 10 millimols per liter. We wanted to study metformin activity under these conditions," Thor says.

So the question was this: how would metformin perform in breast cancer cells grown at more realistic, human levels of glucose?

"Results show that when you drop glucose down to human levels, metformin has an even bigger effect at standard doses. When glucose is high you need more metformin to achieve the same results," Thor says.

Thor also points out that skeptics of metformin treatment for cancer in general or breast cancer in particular frequently point to the high concentrations of metformin needed to create results in the laboratory.

"Our data helps to explain why higher doses of metformin are required to obtain anti-cancer effects when cancer cells are grown in the lab, as compared to its use in humans," Thor says.

Interestingly, "it wasn't simply that the metformin effectiveness went up as glucose came down, but that entirely new mechanisms of action were present at lower glucose levels," Thor says.

Specifically, Thor and colleagues used RNA expression arrays to discover which genes were affected by metformin at high and low glucose concentrations. At high glucose concentrations, metformin primarily affected genes involved in metabolic processes and cell proliferation; at low glucose concentrations, metformin affected genes controlling cellular process and programmed cell death.

In addition to affecting the growth of breast cancer cells, Thor and colleagues show the drug decreases the ability of breast cancer cells to move within the body – a task necessary for the spread of the disease to other sites.

"An extension of this data implies that in breast cancer patients with diabetes or metabolic syndrome, metformin may less effective at the standard dose. To be effective, doctors may have to first explore glucose control or may have to use a higher dose of metformin," Thor says.

### END


ELSE PRESS RELEASES FROM THIS DATE:

NEJM study exposes overuse of radiation therapy when urologists profit from self-referral

2013-10-24
NEJM study exposes overuse of radiation therapy when urologists profit from self-referral IMRT use is 2 1/2 times greater when self-referral's financial incentives are involved Fairfax, Va., October 23, 2013—A comprehensive review of Medicare ...

UCLA sleep apnea study uncovers more hidden dangers for women

2013-10-24
UCLA sleep apnea study uncovers more hidden dangers for women There's more bad news for women with sleep apnea. A new study from the UCLA School of Nursing shows that the body's autonomic responses — the controls that impact such functions as blood ...

USC study: Google search serves users from 600 percent more locations than a year ago

2013-10-24
USC study: Google search serves users from 600 percent more locations than a year ago In a shift in strategy, Google reuses existing content delivery infrastructure to speed up searches Over the past 10 months, Google search has dramatically increased the ...

Data reaffirms test's ability to identify benign thyroid nodules

2013-10-24
Data reaffirms test's ability to identify benign thyroid nodules Study co-led by a CU School of Medicine researcher has confirmed that a Gene Expression Classifier test can drastically reduce the problem of unnecessary surgeries in thyroid nodule ...

CU-Boulder study shows unprecedented warmth in Arctic

2013-10-24
CU-Boulder study shows unprecedented warmth in Arctic Last 100 years may be warmest in 120,000 years The heat is on, at least in the Arctic. Average summer temperatures in the Eastern Canadian Arctic during the last 100 years are higher now than ...

Gene-diet interaction may help explain link between eating meat & colorectal cancer risk

2013-10-24
Gene-diet interaction may help explain link between eating meat & colorectal cancer risk Findings may have public health significance since diet is modifiable risk factor for colorectal cancer A newly discovered potential gene-diet interaction for colorectal ...

Mutations in novel tumor suppressor gene associated with early onset breast cancer

2013-10-24
Mutations in novel tumor suppressor gene associated with early onset breast cancer RINT1 gene variants also may play role in other cancers An international team of scientists has identified an association between heritable, rare mutations in the RINT1 gene ...

BROCA sequencing approach evaluates all 24 genes implicated in breast cancer

2013-10-24
BROCA sequencing approach evaluates all 24 genes implicated in breast cancer Explains occurrence of breast cancer in women with normal BRCA genes, scientists report at ASHG 2013 Since 1994, many thousands of women with breast cancer from families severely ...

Gene variants in immune system pathways are correlated with composition of microbes of human body

2013-10-24
Gene variants in immune system pathways are correlated with composition of microbes of human body These genes are significantly enriched in inflammatory and immune pathways Human genes in immunity-related pathways are likely associated with the composition ...

UMass Amherst researcher quantifies the effectiveness of video ads

2013-10-24
UMass Amherst researcher quantifies the effectiveness of video ads Perhaps the largest-ever scientific study of the effectiveness of video ads addresses a key question for advertisers who want to capitalize on online video, the 'killer app' of ...

LAST 30 PRESS RELEASES:

The most effective diabetes drugs don't reach enough patients yet

Breast cancer risk in younger women may be influenced by hormone therapy

Strategies for staying smoke-free after rehab

Commentary questions the potential benefit of levothyroxine treatment of mild hypothyroidism during pregnancy

Study projects over 14 million preventable deaths by 2030 if USAID defunding continues

New study reveals 33% gap in transplant access for UK’s poorest children

Dysregulated epigenetic memory in early embryos offers new clues to the inheritance of polycystic ovary syndrome (PCOS)

IVF and IUI pregnancy rates remain stable across Europe, despite an increasing uptake of single embryo transfer

It takes a village: Chimpanzee babies do better when their moms have social connections

From lab to market: how renewable polymers could transform medicine

Striking increase in obesity observed among youth between 2011 and 2023

No evidence that medications trigger microscopic colitis in older adults

NYUAD researchers find link between brain growth and mental health disorders

Aging-related inflammation is not universal across human populations, new study finds

University of Oregon to create national children’s mental health center with $11 million federal grant

Rare achievement: UTA undergrad publishes research

Fact or fiction? The ADHD info dilemma

Genetic ancestry linked to risk of severe dengue

Genomes reveal the Norwegian lemming as one of the youngest mammal species

Early birds get the burn: Monash study finds early bedtimes associated with more physical activity

Groundbreaking analysis provides day-by-day insight into prehistoric plankton’s capacity for change

Southern Ocean saltier, hotter and losing ice fast as decades-long trend unexpectedly reverses

Human fishing reshaped Caribbean reef food webs, 7000-year old exposed fossilized reefs reveal

Killer whales, kind gestures: Orcas offer food to humans in the wild

Hurricane ecology research reveals critical vulnerabilities of coastal ecosystems

Montana State geologist’s Antarctic research focuses on accumulations of rare earth elements

Groundbreaking cancer therapy clinical trial with US Department of Energy’s accelerator-produced actinium-225 set to begin this summer

Tens of thousands of heart attacks and strokes could be avoided each year if cholesterol-lowering drugs were used according to guidelines

Leading cancer and metabolic disease expert Michael Karin joins Sanford Burnham Prebys

Low-intensity brain stimulation may restore neuron health in Alzheimer's disease

[Press-News.org] Study: Metformin for breast cancer less effective at higher glucose concentrations