Hungry For Sugar

August 27, 2009 | Filed Under PET CT Scan, cancer, research | No Comments

University of Utah biochemists have made a breakthrough in understanding how cancer cells feed on glucose, possibly paving the way for new drugs designed to starve cancer into submission.

Cancer cells use glucose in tandem with another crucial nutrient, the protein glutamine, an amino acid found in many foods, according to findings published this week by researchers at the Huntsman Cancer Institute. The findings could spur development of new chemotherapies that would stall tumor growth by deactivating cancer cells’ ability to use glucose, said Don Ayer, a professor of oncological sciences whose lab published the research in the Proceedings of the National Academy of Science .

For decades, science has known that cancer cells suck up inordinate quantities of glucose, nature’s ubiquitous biological fuel, in a process that quickly blows tiny tumors into deadly malignancies.

PET scans use cancer cells’ high rate of glucose metabolism to build images of tumors. These cells also need glutamine, just like normal cells.

“It’s absolutely clear you need both for tumor growth. They seem to need it more than other nutrients. If you deprive them of one or the other, tumors don’t grow,” Ayer said.

Mohan Kaadigea, a postdoctoral researcher in Ayer’s lab, spearheaded the study, whose co-authors include Ayer; Sadhaasivam Kamalanaadhana, also a member of the Ayer lab; and Ryan Looper, an assistant professor in the Department of Chemistry.

The lab’s work, funded by the National Institutes of Health and the American Cancer Society, seeks to unlock the molecular mysteries associated with tumor proliferation.

“Research into the factors that regulate the metabolism and growth of cancer cells is still at an early stage,” said Janet Shaw, a U. professor in the Department of Biochemistry and a former Huntsman researcher. “Dr. Ayer’s discovery that glutamine and glucose utilization are linked is important because it identifies a number of new molecular targets that could be manipulated to interfere with the growth and survival of tumor cells.”

This week’s discovery builds on the lab’s previous research identifying the role of MondoA, a protein that switches genes on and off, in tumorigenesis. This protein affects the gene TXNIP, which suppresses tumor growth by blocking glucose uptake into cancer cells. The Ayer team discovered that in the presence of glutamine, MondoA deactivates TXNIP. This is important because it suggests new ways to impede tumor growth.

“If you don’t have glutamine, the cell is short-circuited due to a lack of glucose, which halts the growth of the tumor cell,” Ayer said.

The next step is to learn how the Mondo protein works in relationship with glutamine.

“If you can modify the metabolism of the tumor cell you can have a benefit. This is not a new idea,” Ayer said. “If we can figure out how glutamine signals to Mondo, that has quite a bit of chemotherapeutic potential.”

Were it developed, a drug that blocks glucose uptake would not likely choke off normal cell growth, as many cancer chemotherapy drugs currently do because of their toxicity.

“Tumor cells seem to be addicted to glucose. Normal cells are not. They grow at a slower rate and if you challenge them with nutrient deprivation they can be more flexible,” Ayer said.

Ayer emphasized that his lab’s findings shed no light on dietary impacts on tumor growth. Glutamine is the most common amino acid in our bodies and glucose levels are tightly regulated by our endocrine system, regardless of sugar consumption.

Cancer and diet

The fact that cancer cells might die if deprived of glucose doesn’t mean cancer patients should cut sugar out of their diets, researchers say.

Cancer patients should eat a balanced diet to promote good health. Cutting out sugar would not inhibit tumor growth, said Don Ayer, a professor of oncological sciences at the Huntsman Cancer Institute. Even with a sugar-free diet, there still would be plenty of glucose in the blood to feed cancer.

Cancer Survivors at Risk for Psychological Distress

August 10, 2009 | Filed Under cancer, health, prognosis, research, stress | No Comments

According to a report in the July 27 issue of Archives of Internal Medicine, long-term survivors of adulthood-onset cancer are at increased risk of experiencing serious psychological distress.

The estimated 12 million cancer survivors in the United States represent approximately 4 percent of the population, according to background information in the article. “The number of cancer survivors has steadily increased over the last three decades and is expected to continue to increase with the implementation of improved cancer screening, the adoption of more efficacious cancer treatment and the aging of the population,” the authors write. “As more individuals survive cancer, it is important to understand how cancer and cancer therapies affect long-term quality of life and psychological adjustment.”

Karen E. Hoffman, M.D., M.H.Sc., of Brigham and Women’s Hospital and Dana-Farber Cancer Institute, Boston, and colleagues studied participants in the National Health Interview Survey, a cross-sectional in-person survey conducted annually by the U.S. Census Bureau. Participants in the 2002 to 2006 surveys were asked questions about their history of cancer and assessed using a scale of serious psychological distress. The researchers compared the responses of 4,636 individuals who had survived five years or longer following the diagnosis of an adult-onset cancer with those of 122,220 individuals who had never had cancer.

A total of 5.6 percent of cancer survivors screened positive for severe psychological distress within the previous 30 days, compared with 3 percent of those without cancer. “After adjustment for other clinical and sociodemographic variables, long-term survivors who were younger, were unmarried, had less than a high school education, were uninsured, had more comorbidities or had difficulty performing instrumental activities of daily living were more likely to experience serious psychological distress,” the authors write.

A history of cancer may affect current mental health in several ways, the authors note. “Cancer diagnosis and treatment can produce delayed detrimental effects on physical health and functioning such as secondary cancers, cardiac dysfunction, lung dysfunction, infertility, neurological complications and neurocognitive dysfunction,” they write. “A cancer history can also affect social adaptation, employment opportunities and insurance coverage. Adjusting to these functional and life limitations may create long-term psychological stress.”

A total of 9 percent of long-term cancer survivors and 6 percent of individuals without cancer reported seeing or talking to a mental health professional within the previous 12 months. One-third of survivors with serious psychological distress reported using mental health services, whereas 18 percent said they could not afford mental health care during the previous year.

“Because long-term survivors may not be seen by oncologists as frequently as they were during treatment, or at all, the increased risk of serious psychological distress and the need to screen for serious psychological distress should be communicated to primary care physicians and other care providers,” the authors conclude. “Given that cancer survivors with more chronic medical conditions tended to be those most at risk for psychological distress in this study, the findings also underscore the need to integrate medical and behavioral health care for survivors. Specifically, cancer survivorship clinics may benefit from having mental health providers on staff for a multidisciplinary approach to the care of these patients.”

I’m Confused

August 6, 2009 | Filed Under ENT, PET CT Scan, oncologist | No Comments

The Monday following my last PET Scan, I received this ominous call from my ENT’s office telling me that “Dr. Breslier would like to see” me in his office ASAP. Although, the PET Scan wasn’t mentioned, I knew from bitter experience that doctor’s don’t normally ring you up out-of-the-blue with that sense of urgency to give you good news, so in the time between the phone call and my appointment later in the week, I became very worried.

Well, when I saw the doctor, the build-up ended-up being much ado about nothing — although, when he first addressed the PET Scan he did make it sound like there was a problem. Basically, the PET Scan was similar to the 2 previous scans in that it showed some activity in the area where the largest tumor had been. He ultimately said it was nothing to worry about and that if I had 100 PET Scans it would probably say the same thing but that, after two years it’s not likely that the cancer has returned. Still, I left his office feeling a little weird about it. I had this idea that maybe one of my oncologists had pressed him on the phone about his latest scan. Radiologists don’t always write the most straightforward reports and while one radiologist can look at something and see nothing significant, another might suggest otherwise to cover their own ass, just in case. I surmised that this might be the case. When this issue first cropped up a year ago, the alarm bells went off because the radiologist wrote an ambiguously worded report. The PET last winter yielded the same result as the previous one, but a different radiologist and a more straightforward report. This last one? I have no idea.

What I find confused is that yesterday, when I saw my oncologist, he said that he hadn’t even received the PET Scan report. He wasn’t happy about that either. He called the Cancer Center and read them the riot act and had the report faxed to his office while I waited in the exam room. He read the report and said “everything’s fine.” So I am puzzled. If the report said that there’s no indication of cancer, why the lengthy build-up from my ENT suggesting that the report said otherwise. And, more importantly, why was my oncologist — who should have received the report when my other doctors received it, excluded? It’s a mystery.