MSCs: what’s in a name?

Whether they are "stem" or "stromal", from adult tissues or from umbilical cord blood, MSCs are being used for a lot of clinical trials. Read more

Mopping up immune troublemakers after transplant

Memory CD8+ T cells play an important role in kidney transplant rejection, and they resist drugs that would otherwise improve Read more

Tracking a frameshift through the ribosome

Ribosomal frameshifting, visualized through X-ray Read more

radiation

SUMO wrestling enzyme important in DNA repair

The DNA in our cells is constantly being damaged by heat, radiation and other environmental stresses, and the enzyme systems that repair DNA are critical for life. A particularly toxic form of damage is the covalent attachment of a protein to DNA, which can be triggered by radiation or by anticancer drugs.

Keith Wilkinson, PhD

Emory biochemist Keith Wilkinson and colleagues have a paper this week in the journal eLife probing how a yeast protein called Wss1 is involved in repairing DNA-protein crosslinks. The researchers show how Wss1 wrestles with a protein tag called SUMO on the site of the DNA damage, and how Wss1 and SUMO are involved in the cleanup process.

Three interesting things about this paper:

*The paper grew out of first author Maxim Balakirev’s sabbatical with Wilkinson at Emory. Balakirev’s home base is at the CEA (Alternative Energy and Atomic Energy Commission) in Grenoble, France.

* Since many cancer chemotherapy drugs induce protein-DNA cross links, an inhibitor of cross link repair could enhance those drugs’ effectiveness. On the other side of the coin, mutations in a human gene called Spartan, whose sequence looks similar to Wss1’s, cause premature aging and susceptibility to liver cancer. Whether the Spartan-encoded protein has the same biochemical activity as Wss1 is not yet clear.

*SUMO stands for “small ubiquitin-like modifier”. The eLife digest has an elegant explanation of what’s happening: 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

Proton Therapy and Its Importance to Georgia

From Clinic to You

By Walter J. Curran, Jr., MD
Executive Director, Winship Cancer Institute
Chair, Department of Radiation Oncology, Emory University School of Medicine

Walter J. Curran, Jr., MD

Walter J. Curran, Jr., MD

Emory Healthcare is a key player in plans to bring the world’s most advanced radiation treatment for cancer patients to Georgia.  Emory Healthcare has signed a letter of intent with Advanced Particle Therapy, LLC, of Minden, Nevada, opening the door to a final exploratory phase for development of The Georgia Proton Treatment Center – Georgia’s first proton therapy facility.

For certain cancers, proton therapy offers a more precise and aggressive approach to destroying cancerous and non-cancerous tumors, as compared to conventional X-ray radiation. Proton therapy involves the use of a controlled beam of protons to target tumors with precision unavailable in other radiation therapies. According to The National Association for Proton Therapy, the precise delivery of proton energy may limit damage to healthy surrounding tissue, potentially resulting in lower side effects to the patient. This precision also allows for a more effective dose of radiation to be used.

Proton therapy is frequently used in the care of children diagnosed with cancer, as well as in adults who have small, well-defined tumors in organs such as the prostate, brain, head, neck, bladder, lungs, or the spine.  And research is continuing into its efficacy in other cancers.

The gantry, or supporting structure, of a proton therapy machine.

The gantry, or supporting structure, of a proton therapy machine.

The closest proton therapy facility to Georgia is the University of Florida Proton Therapy Institute in Jacksonville.  Currently there are only nine proton therapy centers in the United States, including centers at Massachusetts General Hospital, MD Anderson Cancer Center in Houston and the University of Pennsylvania.

This is an exciting development in our ability to offer not only patients throughout Georgia and the Southeast the widest possible array of treatment options but patients from around the world who can come to Atlanta via the world’s busiest airport, Hartsfield-Jackson International. In addition, we will work to expand its utility and access for patients through collaborative research projects with Georgia Tech and other institutions. Winship physicians will also be able to reach out to their international colleagues and provide direction in how best to study and implement this technology in the care of cancer patients.

Under the letter of intent, Emory Healthcare faculty and staff will provide physician services, medical direction, and other administrative services to the center. Advanced Particle Therapy, through a Special Purpose Company, Georgia Proton Treatment Center, LLC, (GPTC) will design, build, equip and own the center.  The facility, which will be funded by GPTC, will be approximately 100,000 square feet and is expected to cost approximately $200 million.  Site selection for the facility is underway, and pending various approvals, groundbreaking is expected in the Spring of 2012.

Video

The follow video presents a 3D simulation of proton therapy technology.

Additional Information:

Posted on by Vince Dollard in Uncategorized 1 Comment

Stereotactic radiosurgery: fast, friendly, focused

Cynthia Anderson, MD

When Cynthia Anderson, MD, prepares her patients for stereotactic radiosurgery she emphasizes three things: the surgery is fast, friendly and focused. Initially used to treat the part of the brain associated with brain tumors, stereotactic radiosurgery has gained currency as a treatment for various types of cancer. This type of surgery uses x-ray beams instead of scalpels to eliminate tumors of the liver, lung and spine.

“It’s fast because the actual radiation treatment itself is very short,” says Anderson, a radiation oncologist at the Winship Cancer Institute of Emory University. “It’s friendly because it’s all done as an outpatient. And it’s focused because these targeted radiation beams get the maximum dose of radiation to a tumor and give the most minimal dose of radiation to the critical organs that surround the tumor.”

Read more

Posted on by Robin Tricoles in Uncategorized Leave a comment

Childhood cancer treatment may raise diabetes risk

Cancer survivors who got radiation treatments as children have nearly twice the risk of developing diabetes as adults. That’s according to a study led by Emory and Children’s Healthcare of Atlanta pediatric oncologist Lillian R. Meacham, MD.

Lillian Meacham, MD

Lillian Meacham, MD

The study, published in the August 10/24 issue of Archives of Internal Medicine, compared rates of diabetes in nearly 8,600 childhood cancer survivors diagnosed between 1970 and 1986, and nearly 3,000 of their siblings who did not have cancer.

Children who were treated with total body radiation or abdominal radiation to fight off cancer appear to have higher diabetes risks later in life, regardless of whether they exercise regularly or maintain a normal weight.

After adjusting for other risk factors, including body mass index – a ratio of height and weight – Meacham and team found that childhood cancer survivors overall were 1.8 times more likely to have diabetes.

And the more radiation that was used, the greater the diabetes risk. For those treated with total body radiation — a treatment often used before bone marrow transplants to treat childhood leukemia — the diabetes risk was more than seven times greater.

More study is needed to understand how radiation could promote diabetes in cancer survivors, notes Meacham.

She says it is imperative that clinicians recognize this risk, screen for diabetes and pre-diabetes when appropriate, and approach survivors with aggressive risk-reducing strategies.

Meacham is a professor of pediatrics in the Emory School of Medicine and medical director of the Cancer Survivor Program with the AFLAC Cancer Center and Blood Disorders Services, Children’s Healthcare of Atlanta.

Posted on by adobbs in Uncategorized Leave a comment