Mitochondrial blindness -- Newman's Emory story

Neuro-ophthalmologist Nancy Newman’s 2017 Dean’s Distinguished Faculty Lecture and Award were unexpectedly timely. Her talk on Tuesday was a tour of her career and mitochondrial disorders affecting vision, culminating in a description of gene therapy clinical trials for the treatment of Leber’s hereditary optic neuropathy. The sponsor of those studies, Gensight Biologics, recently presented preliminary data on a previous study of their gene therapy at the American Academy of Neurology meeting in April. Two larger trials Read more

IMSD program nurtures young scientists

The IMSD (Initiative to Maximize Student Development) program nurtures and mentors a diverse group of young scientists at Read more

Flu meeting at Emory next week

We are looking forward to the “Immunology and Evolution of Influenza” symposium next week (Thursday the 25th and Friday the Read more

melanoma

Melanoma mutation likes fat for fuel

Cancer cells love glucose, the simple sugar the body uses for energy, so a high-fat, low-carb diet should starve them, right?

Where does this idea come from? Most cancer cells display enhanced glucose uptake, a phenomenon known as the Warburg effect, after 1931 Nobel Prize winner Otto Warburg.

Resurgent interest in exploiting the Warburg effect was described by Sam Apple in NYT Magazine and by Bret Stetka for NPR. High-fat, low-carb “ketogenic” diets are known to be effective against some types of epilepsy, and have also been explored by endurance athletes. Ketogenic diets have been tried as a clinical countermeasure against cancer in a limited way, mainly in brain cancer.

Before everybody gets too excited, let’s think about how particular cancer-driving mutations affect cell metabolism, suggests Winship Cancer Institute researcher Jing Chen. His team’s work in mice suggests that cancers with a common melanoma mutation (BRAF V600E) will grow faster in response to a ketogenic diet. In addition, the Winship researchers found that lipid-lowering agents such as statins curb these cancers’ growth, even in the context of a more normal diet.

The results were published on January 12 in Cell Metabolism.

Caveats: the findings cover just one mutation and need to be tested clinically.

Consumers and cancer patients already get a lot of advice about the right diet to fight cancer, but this research points toward an intriguing concept:  a “precision diet,” tailored to an individual patient’s cancer.  Read more

Posted on by Quinn Eastman in Cancer Leave a comment

Melanoma mutation rewires cell metabolism

A mutation found in most melanomas rewires cancer cells’ metabolism, making them dependent on a ketogenesis enzyme, researchers at Winship Cancer Institute of Emory University have discovered.

The V600E mutation in the gene B-raf is present in most melanomas, in some cases of colon and thyroid cancer, and in the hairy cell form of leukemia. Existing drugs such as vemurafenib target the V600E mutation — the finding points to potential alternatives or possible strategies for countering resistance. It may also explain why the V600E mutation in particular is so common in melanomas.

Researchers led by Jing Chen and Sumin Kang have found that by promoting ketogenesis, the V600E mutation stimulates production of a chemical, acetoacetate, which amplifies the mutation’s growth-promoting effects. (A feedback mechanism! Screech!)

The results were published Thursday, July 2 in Molecular Cell.

More on this paper here.

Posted on by Quinn Eastman in Cancer 1 Comment

Explainer: oncolytic viruses

A recent publication from Bill Kaiser’s and Ed Mocarski’s labs in Cell Host & Microbe touches on a concept that needs explaining: oncolytic viruses.

Viruses have been subverting the machinery of healthy cells for millions of years, and many viruses tend to infect particular tissues or cell types. So they are a natural starting point for researchers to engineer oncolytic viruses, which preferentially infect and kill cancer cells.

Several oncolytic viruses have progressed to advanced clinical trials. Amgen’s “T-Vec”, a modified herpes simplex virus, could be the first to be approved by the FDA this year based on its efficacy against metastatic melanoma.  Read more

Posted on by Quinn Eastman in Cancer Leave a comment

Cancer immunotherapy, meet chimera

697px-Chimera_d'arezzo,_fi,_03

In Greek mythology, the chimera was a monstrous fire-breathing creature composed of the parts of three animals: a lion, a snake and a goat.

Adoptive cell transfer is advancing as a cancer immunotherapy technique. It involves removing some of a patient’s immune cells, culturing them in the laboratory, and then infusing the cells back into the patient. The idea is to enhance the ability of the immune cells to attack the tumors far beyond what the immune system was able of doing on its own.

Two promising examples are the National Cancer Institute’s approach of treating advanced melanoma with IL-2-stimulated immune cells, and several investigators’ approach of genetically engineering T cells to attack leukemias or lymphomas.

Jacques Galipeau and colleagues at Winship Cancer Institute have developed a chimeric molecule for stimulating immune cells, which appears to have unique powers beyond simply the sum of its two parts. The molecule is called GIFT4, a fusion of the immune signaling molecules GM-CSF (often used in cancer treatment) and IL-4.

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Posted on by Quinn Eastman in Cancer, Immunology Leave a comment

Cancer’s shield: PD-1

Gina Kolata has a section front story in Tuesday’s New York Times exploring the potential of a relatively new class of anticancer drugs. The drugs break through “shields” built by cancers to ward off the threat posed by the patient’s immune system. Many are based on blocking PD-1, an immune regulatory molecule whose importance in chronic infections was first defined by Emory’s Rafi Ahmed.

Of course, not every cancer research development described as transformative in the New York Times lives up to the hype. But the clinical trial results, reported in the New England Journal of Medicine, are solid enough that the researchers Kolata talks with think they are seeing “a moment in medical history when everything changed.” [Winship Cancer Institute’s John Kauh was a co-author on one of the 2012 NEJM papers.]

Let’s take a moment to examine some of the roots of this story. Rafi Ahmed didn’t set out to study cancer. For the last two decades, he and his colleagues have been studying T cells, parts of the immune system that are critical for responding to infections. Read more

Posted on by Quinn Eastman in Cancer, Immunology 2 Comments

Making “death receptor” anticancer drugs live up to their name

Cancer cells have an array of built-in self-destruct buttons called death receptors. A drug that targets death receptors sounds like a promising concept, and death receptor-targeting drugs have been under development by several biotech companies. Unfortunately, so far results in clinical trials have been disappointing, because cancer cells appear to develop resistance pathways.

Death receptor-targeting drugs under development include: drozitumab, mapatumumab, lexatumumab, AMG655, dulanermin.

Winship Cancer Institute researcher Shi-Yong Sun, PhD and colleagues have a paper in Journal of Biological Chemistry that may help pick the tumors that are most likely to be vulnerable to death receptor-targeting drugs. This could help clinical researchers identify potential successes ahead of time and maximize chances of a good response for patients.

Postdoctoral fellow Youtake Oh is the first author. Winship deputy director Fadlo Khuri, MD and Taofeek Owonikoko, MD, PhD, co-chair of Winship’s clinical and translational research committee, are co-authors. Khuri’s 2010 presentation on death receptor drugs and lung cancer is available here (PDF).

Sun’s team shows that mutations in the cancer-driving genes Ras and B-Raf both induce cancer cells to make more of one of the death receptors (death receptor 5). In addition, they show that cancer cells with mutations in Ras or B-Raf tend to be more vulnerable to drugs that target death receptor 5.

Shi-Yong Sun, PhD

These mutations are known to be more common in some types of cancer. For example, roughly half of melanomas have mutations in B-Raf. Vemurafenib, a drug that inhibits mutated B-Raf, was approved in August 2011 for the treatment of melanoma. K-ras mutations are similarly abundant in lung cancer.

The selection and targeting of tumors via their specific mutations is a growing trend. Sun says lung, colon and pancreatic cancer are all cancer types where Ras and Raf mutations are common enough to become useful biomarkers. In lung cancer, Sun’s team’s results could be especially welcome news because, as a 2009 review concluded:

Recent studies indicate that patients with mutant KRAS tumors fail to benefit from adjuvant chemotherapy, and their disease does not respond to EGFR inhibitors. There is a dire need for therapies specifically for patients with KRAS mutant NSCLC.

 

Posted on by Quinn Eastman in Cancer Leave a comment

Sunscreen: Looking Beyond the Numbers

Carl Washington, MD

Seems pretty obvious – if a sunscreen with an SPF of 30 is good, then an SPF of 100 should be at least three times as good.

Unfortunately, that is not the case.  There are other important details to consider when you are purchasing a sunscreen.

“People have become much more educated about the importance of using sunscreen, and manufacturers have responded with an abundance of products,” says Carl Washington, MD, associate professor of Dermatology at Emory University School of Medicine. “Unfortunately, the labeling can be confusing and many of the current sunscreens only contain the ingredients necessary to offer protection against sunburn, but not skin cancer or aging.”

Recently, the Food and Drug Administration created new regulations to establish standards for sunscreen manufacturers to follow before they label their products.

Under the new regulations, which will go into effect in 2012, sunscreen products that protect against all types of sun-induced skin damage will be labeled “broad spectrum” and “SPF 15” or higher on the container. Only products that have been tested to ensure they protect against both UVA (ultraviolet radiation A) and UVB (ultraviolet radiation B) radiation will be allowed to use this labeling.  Broad-spectrum sunscreens of SPF 15 and higher can also be labeled as protective against skin cancer and premature aging. The maximum SPF value is set at 50-plus because the FDA says anything higher doesn’t provide a significant amount of additional protection.

Manufacturers will have to include warning labels on products that are not broad spectrum. Products that claim to be water resistant must indicate how long the consumer should expect to be protected in the water, and using such language as “waterproof” or “sweat proof” will not be allowed.

“Skin cancer is the most common form of cancer in the United States, and the number of people affected keeps rising. Simply getting into the habit of using a sunscreen every day – with the appropriate levels of protection – can make a significant difference in preventing many skin cancers, as well as premature aging,” says Washington.

“These new regulations will help consumers understand the difference in degrees of sun protection, and choose carefully.”

Washington also suggests staying out of direct sunlight between 10 am and 2 pm, seeking shade when you are outdoors, remembering to reapply sunscreen every two hours and wearing protective clothing.

Posted on by Kathi Baker in Uncategorized Leave a comment

Eye diseases and immune system link studied

Drawing shows areas of the eye

Emory Eye Center researchers are looking at the role of the immune system in the inflammation of the eye and the progression of eye diseases.

Santa Ono, PhD, professor of ophthalmology, Emory School of Medicine and researcher at the Emory Eye Center, and Emory senior vice provost for undergraduate education and academic affairs, and his team at the R. Howard Dobbs Jr. Ocular Immunology Lab, focus on the immune component of age-related macular degeneration (AMD), ocular cancer (melanoma and retinoblastoma) and ocular inflammation.

Santa J. Ono, PhD

Macular degeneration is the leading cause of sight impairment and blindness in older people. The macula, in the center of the retina, is the portion of the eye that allows for the perception of fine detail. AMD gradually destroys a person’s central vision, ultimately preventing reading, driving, and seeing objects clearly

In a recent article of Emory Magazine, Ono, an ocular immunologist, says, “If a person with AMD looks at graph paper, some of the lines will be wavy instead of straight. Certain parts of the image are no longer being transferred to the brain.”

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Posted on by Joy Bell in Uncategorized Leave a comment