Exosomes as potential biomarkers of radiation exposure

Exosomes = potential biomarkers of radiation in the Read more

Before the cardiologist goes nuclear w/ stress #AHA17

Measuring troponin in CAD patients before embarking on stress testing may provide Read more

Virus hunting season open

Previously unknown viruses, identified by Winship + UCSF scientists, come from a patient with a melanoma that had metastasized to the Read more

urology

Frailty: we know it when we can measure it

One of Lab Land’s regular features is a post exploring a biomedical term that seems to be appearing frequently in connection with Emory research. This month I’d like to focus on frailty, which has been an important concept in treating elderly patients for some time. (This piece in The Atlantic nudged me into it.) Assessing frailty is emerging as a way for surgeons to predict post-operative complications.

Several teams of researchers have been trying to develop a standardized way of measuring frailty to aid in weighing the risks and benefits of surgery. Frailty may seem like a subjective quality (echoing Supreme Court Justice Potter Stewart’s remarks on obscenity: “I know it when I see it”) but if frailty can be defined objectively, doctors and patients can use it to help in decision-making.

Frailty can be thought of as a decrease in physiological reserve or a decrease in the ability to recover from an infection or injury. Much of the credit for developing the concept of frailty should go to Linda Fried, now dean of Columbia’s school of public health. While at Johns Hopkins, her team developed the Hopkins Frailty Score: a composite based on recent weight loss, self-reported exhaustion, low daily activity levels, low grip strength and slow gait. Read more

Posted on by Quinn Eastman in Uncategorized Leave a comment

Statins, prostate cancer and mitochondria

In honor of Fathers’ Day, we are examining a connection between two older-male-centric topics: statins and prostate cancer.

Statins are a very widely prescribed class of drugs used to lower cholesterol levels, for the purpose of preventing cardiovascular disease. In cell culture, they appear to kill prostate cancer cells, but the epidemiological evidence is murkier. Statin effects on prostate cancer incidence have been up in the air, but recent reports point to the possibility that starting statins may slow progression, after a man has been diagnosed with prostate cancer.

Winship Cancer Institute researchers have some new results that shed some light on this effect. John Petros, Rebecca Arnold and Qian Sun have found that mutations in mitochondrial DNA make prostate cancer cells resistant to cell death induced by simvastatin [Zocor, the most potent generic statin]. Sun recently presented the results at the American Urological Association meeting in Orlando.

In other forms of cancer such as breast and lung cancer, genomic profiling can determine what DNA mutations are driving cancer growth and what drugs are likely to be effective in fighting the cancer. The prostate cancer field has not reached the same point, partly because prostate cancers are not generally treated with chemotherapy until late in the game, Petros says. But potentially, information on mitochondrial mutations could guide decisions on whether to initiate statin (or another) therapy.

“This is part of our soapbox,” he says. “When we are looking at mutational effects on prostate cancer, let’s be sure to include the mitochondrial genome.”

Winship’s Carlos Moreno and his colleagues are working on the related question of biomarkers that predict prostate cancer progression, after prostatectomy surgery and potentially after just a biopsy.

Read more

Posted on by Quinn Eastman in Cancer Leave a comment

Highlights and links from PSA debate

On January 8, Emory University School of Medicine’s Department of Medicine Grand Rounds had an unusual format: a debate between Otis Brawley, MD and John Petros, MD on the topic of PSA testing.

Otis Brawley, MD

Prostate cancer is the second leading cause of cancer death for American men. PSA (prostate specific antigen) is a protein produced by the prostate gland and its levels can be measured by a simple blood test.  A higher number could indicate prostate cancer, but the test doesn’t differentiate between an aggressive, fast-growing cancer, and one that is so slow-growing it wouldn’t threaten a man’s life.

Brawley, professor of hematology and medical oncology and chief medical officer for the American Cancer Society, led off the debate arguing that studies show PSA testing to be unreliable and possibly leading to too many diagnoses and unnecessary treatment for prostate cancer. Petros, a professor of urology who treats prostate cancer patients, looked at other studies (more details below), which show the PSA test to be a tool that has helped save lives by detecting prostate cancer at earlier stages.

In May 2012, the U.S. Preventive Services Task Force issued a “grade D” rating for PSA screening, saying the practice offers more harms — in terms of complications from PSA-test-driven treatment such as incontinence and blood clots — than benefits. Brawley agreed with this Ray Ban outlet assessment and says he’s not convinced the PSA test saves lives, but he doesn’t rule out its use. He framed this issue this way:

Pretend you are offered the choice of taking a pill that will double the risk of prostate cancer diagnosis from 10 to 20 percent, but could decrease risk of prostate cancer death by one fifth: from 3 to 2.4 percent.  “Do you feel lucky?” Brawley quipped.

John Petros, MD

As a counterpoint, Petros cited National Cancer Institute epidemiology data indicating that the rate of metastatic prostate cancer has substantially decreased over the last few decades, since prostate cancers are now being diagnosed at an earlier stage. He also went over studies conducted in Sweden (Goteborg) and in Austria (Tyrol), which show significant reductions in prostate cancer-related mortality coming from PSA testing.

Five things Brawley and Petros agreed on:

  1. PSA testing should be performed in the context of a physician-patient relationship, with men making an informed decision about the value of the information they will receive and the associated risks.
  2. Vans in supermarket parking lots – more broadly, community- or employer-based screening  — are not the ideal setting for PSA testing.
  3. The PLCO study, a NCI-sponsored randomized clinical trial to examine the effects of screening on cancer-related mortality, was flawed. In particular, the “control” arm had a substantial rate of PSA testing.
  4. Brawley said: “Some cancers that are detected early do not pose a threat and do not need to be treated.” Similarly, Petros said: “Prostate cancer can be low risk if safely observed, but high risk forms are lethal. We need to focus on cancers that matter.”
  5. Biomarkers that are better than PSA alone are needed. Brawley said: “We need a 2013 definition of prostate cancer, informed by genomics, rather than going by what Virchow decided prostate cancer looks like under the microscope 160 years ago.”

Petros agreed with this last point and noted that more sophisticated tests than PSA already have been identified such as the prostate health index, which measures levels for three forms of PSA and may be more cancer-specific. Research being conducted at Emory by Carlos Moreno and colleagues also moves toward this goal. In 2011, his team published results in the American Journal of Pathology on a panel of biomarkers that can predict prostate cancer outcomes after prostatectomy. The Atlanta Business Chronicle recently had a story on a patent related to Moreno’s research.

Petros said a key question, and one he and Moreno are planning on testing, is whether the same biomarkers could be useful on prostate biopsy samples. This could help make treatment decisions regarding surgery vs radiation. Biopsy-based tests could be combined with data based on urine biomarkers, to get around the problem of tumor heterogeneity and imperfect sampling, Petros said.

For now, Petros said he believes in initiating a conversation about PSA screening with patients 50 and older, or younger if they have risk factors for the disease.   He said the decision to have routine PSA testing, follow-up tests and prostate cancer treatments, is a very individualized process.

“It comes down to, what do you tell the man standing in front of you?” he said. “You have to consider where they are in life and what their goals are, and that varies with every man.”

Posted on by Quinn Eastman in Cancer Leave a comment

Smoking’s reach – and risk – even broader than we thought

Smoking’s link to lung cancer has been well-known for decades, but we are still learning about its cancer-causing effects on other organs.

An article in the Journal of the American Medical Association (JAMA) provides solid epidemiological evidence that smoking’s link to bladder cancer is even higher than previously believed. And, the elevated risk factor appears to be the same for men and women.

Viraj Master, MD, PhD

“This is something I see in my practice every day,” says Viraj Master, associate professor of urology, Emory School of Medicine and director of urology clinical research at the Winship Cancer Institute of Emory University. “The dangers of smoking are pervasive. Patients are often surprised to hear of the link between smoking and bladder cancer, but it’s there, and it’s a very real risk.”

The bladder may not be the first organ you think about when you think about the harmful effects of cigarette smoking. After all, when a person inhales cigarette smoke, the mouth, throat and lungs are the primary destination. But, a lethal change in the composition of cigarettes makes the bladder a target for cancer.

Written by researchers at the National Cancer Institute, the study explains that while there is less tar and nicotine in cigarettes now that in years passed, there also has been “an apparent increase in the concentration of specific carcinogens,” including a known bladder cancer carcinogen and tobacco-specific nitrosamines. The study authors also note that epidemiological studies have observed higher relative risk rates associated with cigarette smoking for lung cancer.

“The take-home message, of course, is the same as it long has been – don’t start smoking, and if you do smoke, stop,” says Master. “We need to do everything in our power to both stop people from starting to smoke and to help those already addicted to stop.”

Posted on by Kerry Ludlam in Uncategorized Leave a comment