Skin disease studies go deep: depression/inflammation insight

A recent paper from Miller and psychiatry chair Mark Rapaport looks at clinical trials testing an anti-inflammatory drug against psoriasis, to see whether participants’ depressive symptoms improved. Read more

New insight into how brain cells die in Alzheimer's and FTD

(Epi)genetic hallucinations induced by loss of LSD1 resemble Alzheimer's. Another surprise: LSD1 aggregates in Alzheimer's brain, looking like Tau Read more

2B4: potential immune target for sepsis survival

Emory immunologists have identified a potential target for treatments aimed at reducing mortality in sepsis, an often deadly reaction to Read more

Winship Cancer Institute of Emory University

Cancer drug discovery: targeting DNA repair

Standard anticancer treatments, such as chemotherapy, target rapidly dividing cells by damaging their DNA. A newer strategy is to undercut cancer cells’ ability to repair DNA damage.

Radiation oncologist David Yu, MD, PhD

Winship Cancer Institute investigators led by David Yu, MD, PhD have identified a distinct function in DNA double strand break repair for an enzyme called SAMHD1. Depleting or inhibiting SAMHD1 could augment anticancer treatments that induce DNA double-strand breaks, such as ionizing radiation or PARP inhibitor drugs, they suggest. Ionizing radiation is a mainstay of cancer treatment and PARP inhibitors are being developed for several cancer types.

The findings were published this week in Cell Reports (open access).

SAMHD1 was known for its ability to chop up the building blocks of DNA, and had come to the attention of virologists because it limits the ability of retroviruses such as HIV to infect some cell types. The first author of the paper, postdoc Waaqo Daddacha, PhD, previously studied SAMHD1 with virologist Baek Kim, PhD, professor of pediatrics.

Cancer researchers had already sought to harness a retroviral protein called Vpx, which viruses evolved to disable SAMHD1. Acute myeloid leukemia cells use SAMHD1 to get rid of the drug cytarabine, so Vpx can sensitize AML to that drug. The Cell Reports paper shows that virus-like particles carrying Vpx could be deployed against other types of cancer, in combination with agents that induce DNA double-strand breaks. Read more

Posted on by Quinn Eastman in Cancer Leave a comment

To explain cancer biology, use metaphors

Using metaphors to explain biomedical concepts is our bread and butter. That’s why we were tickled to see a recent paper from Winship Cancer Institute bioethicist Rebecca Pentz and colleagues, titled:

Using Metaphors to Explain Molecular Testing to Cancer Patients

Pentz’s team systematically evaluated something that science writers and journalists try to do all the time (and not always well). And they did so with actual conversations between doctors and patients at Winship. The first author of the paper, published in The Oncologist, was medical student Ana Pinheiro.

The researchers studied 66 conversations with nine oncologists. In 25 of those conversations, patients reported that they were able to hear a metaphor. Here’s one example:

“We try to figure out what food makes this kind of cancer grow. For this cancer, the food was estrogen and progesterone. So we’re going to focus on blocking the hormones, because that way we starve the cancer of its food.”

The paper lists all 17 (bus driver, boss, switch, battery, circuit, broken light switch, gas pedal, key turning off an engine, key opening a lock, food for growth, satellite and antenna, interstate, alternate circuit, traffic jam, blueprint, room names, Florida citrus) and how they were used to explain eight cancer-related molecular testing terms.

When patients were asked about the helpfulness of a metaphor that was used, 85 percent of the time they demonstrated understanding and said it was helpful. So let the metaphors fly!

Posted on by Quinn Eastman in Heart Leave a comment

Nutty stimulant revealed as anticancer tool

Arecoline — the stimulant component of areca nuts — has anticancer properties, researchers at Winship Cancer Institute of Emory University have discovered. The findings were published Thursday, November 17 in Molecular Cell.

areca-nut-and-arecoline

Areca nut and chemical structure of arecoline. From Wikimedia.

Areca nuts are chewed for their stimulant effects in many Asian countries, and evidence links the practice to the development of oral and esophageal cancer. Analogous to nicotine, arecoline was identified as an inhibitor of the enzyme ACAT1, which contributes to the metabolism-distorting Warburg effect in cancer cells.

Observers of health news have complained that coffee, as a widely cited example, is implicated in causing cancer one week and absolved the next. Arecoline is not another instance of the same trend, stresses senior author Jing Chen, PhD, professor of hematology and medical oncology at Emory University School of Medicine and Winship Cancer Institute.

“This is just a proof of principle, showing that ACAT1 is a good anticancer target,” Chen says. “We view arecoline as a lead to other compounds that could be more potent and selective.”

Chen says that arecoline could be compared to arsenic, a form of which is used as a treatment for acute promyelocytic leukemia, but is also linked to several types of cancer. Plus, arecoline’s cancer-promoting effects may be limited if it is not delivered or absorbed orally, he says. When arecoline first arose in a chemical screen, Chen says: “It sounded like a carcinogen to me. But it all depends on the dose and how it is taken into the body.” Read more

Posted on by Quinn Eastman in Cancer Leave a comment

Lung cancer cells go amoeboid

Cancer biologists Jessica Konen and Scott Wilkinson, in Adam Marcus’ lab, recently published a paper on the function of LKB1, a gene that is often mutated in lung cancer cells. [Number three behind K-ras and p53.]

Amoeboid

Mesenchymal shape is defined as having a length more than twice the width. Amoeboid looks more like the cell on the right: rounded up. Thanks to Jessica Konen for photo.

Konen and Marcus were featured in a prize-winning video that our team produced last year, which discusses how they developed a technique for isolating “leader cells” — lung cancer cells that migrate and invade more quickly — from a large group and studying those cells’ properties more intensively.

The Molecular Biology of the Cell paper covers a related topic: how LKB1 mutation affects cell shape. In particular, losing LKB1 converts lung cancer cells from a “mesenchymal” morphology to an “amoeboid” morphology.  Read more

Posted on by Quinn Eastman in Cancer Leave a comment

Chasing invasive cancer cells and more at #ASCB15

Earlier today, we posted a notice on Eurekalert for a Sunday, December 13 presentation by graduate student Jessica Konen at the American Society for Cell Biology meeting in San Diego.

Her research, performed with Adam Marcus at Winship Cancer Institute, was the topic of a video that recently won first prize in a contest sponsored by the Association of American Medical Colleges. This was our video team’s first use of the “fast hand on whiteboard” effect, and a lot of fun to make. The video’s strength grows out of the footage Konen and Marcus have of cancer cells migrating in culture. Check it out, if you haven’t already.

Poster presentations at the 2015 ASCB meeting can be found by searching this PDF. A few Emory-centric highlights:

*Chelsey Ruppersburg and Criss Hartzell’s work on the “nimbus”, a torus-shaped structure enriched in proteins needed to build the cell’s primary cilium

*Anita Corbett on how Emory students have a strong record of attaining their own NIH research funding

*Additional work by Adam Marcus’ lab on the tumor suppressor gene LKB1 and how its loss drives lung cancer cells to take on a “unique amoeboid morphology”

*Research from David Katz’s lab on the “epigenetic eraser” LSD1 (lysine-specific demethylase) and its function in neurons and neurodegeneration Read more

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

Graft vs host? Target the aurora

 

Graft-vs-host disease is a common and potentially deadly complication following bone marrow transplants, in which immune cells from the donated bone marrow attack the recipient’s body.

Winship Cancer Institute’s Ned Waller and researchers from Children’s Healthcare of Atlanta and Yerkes National Primate Research Center were part of a recent Science Translational Medicine paper that draws a bright red circle around aurora kinase A as a likely drug target in graft-vs-host disease.

Aurora kinases are enzymes that control mitosis, the process of cell division, and were first discovered in the 1990s in yeast, flies and frogs. Now drugs that inhibit aurora kinase A are in clinical trials for several types of cancer, and clinicans are planning to examine whether the same type of drugs could help with graft-vs-host disease.

Leslie Kean, a pediatric cancer specialist at Seattle Children’s who was at Emory until 2013, is the senior author of the STM paper. Seattle Childrens’ press release says that Kean wears a bracelet around her badge from a pediatric patient cured of leukemia one year ago, but who is still in the hospital due to complications from graft-vs-host. Read more

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

Orange lichens are source for potential anticancer drug

An orange pigment found in lichens and rhubarb called parietin may have potential as an anti-cancer drug, scientists at Winship Cancer Institute of Emory University have discovered.

The results were published in Nature Cell Biology on October 19.

Caloplaca_Fenwick

Parietin, shown to have anticancer activity in the laboratory, is a dominant pigment in Caloplaca lichens. Note: this study did not assess the effects of eating lichens or rhubarb. Photo courtesy of www.aphotofungi.com

Parietin, also known as physcion, could slow the growth of and kill human leukemia cells obtained directly from patients, without obvious toxicity to human blood cells, the authors report. The pigment could also inhibit the growth of human cancer cell lines, derived from lung and head and neck tumors, when grafted into mice.

A team of researchers led by Jing Chen, PhD, discovered the properties of parietin because they were looking for inhibitors for the metabolic enzyme 6PGD (6-phosphogluconate dehydrogenase). 6PGD is part of the pentose phosphate pathway, which supplies cellular building blocks for rapid growth. Researchers have already found 6PGD enzyme activity increased in several types of cancer cells.

“This is part of the Warburg effect, the distortion of cancer cells’ metabolism,” says Chen, professor of hematology and medical oncology at Emory University School of Medicine and Winship Cancer Institute. “We found that 6PGD is an important metabolic branch point in several types of cancer cells.” Read more

Posted on by Quinn Eastman in Cancer Leave a comment

Divide and conquer vs lung cancer

Doctors are using a “divide and conquer” strategy against lung cancer, and in some corners of the battlefield, it’s working. A few mutations – genetic alterations in the tumor that don’t come from the patient’s normal cells — have been found for which drugs are effective in pushing back against the cancer.

However, most lung tumors do not have one of these mutations, and response rates to conventional chemotherapy in patients with advanced lung cancer are poor. Generally, only around 20 percent of patients show a clinical response, in that the cancer retreats noticeably for some time.

Johann Brandes and colleagues at Winship Cancer Institute have been looking for biomarkers that can predict whether an advanced lung tumor is going to respond to one of the most common chemotherapy drug combinations, carboplatin and taxol.

“The availability of a predictive test is desirable since it would allow patients who are unlikely to benefit from this treatment combination to be spared from side effects and to be selected for other, possibly more effective treatments,” Brandes says.

Brandes’ team’s data comes from looking at patients with advanced lung cancer at the Atlanta VAMC from 1999 to 2010. In a 2013 paper in Clinical Cancer Research, the team looked at a protein called CHFR. It controls whether cells can reign in their cycles of cell division while being bombarded with chemotherapy.

In this group being treated with carboplatin and taxol, patients who had tumors that measured low in this protein lived almost four months longer, on average, than those who had tumors that were high (9.9 vs 6.2 months).

His team takes a similar approach in a new paper published in PLOS One. Postdoc Seth Brodie is the first author of the PLOS One paper; he is also co-first author of the CHFR paper along with Rathi Pillai. Read more

Posted on by Quinn Eastman in Cancer Leave a comment

Hold out your finger: Epidemiologist developing test for colon cancer risk

Years from now physicians may be able to determine whether you’re at increased risk for colorectal cancer by drawing blood from the tip of your finger.

Emory University researchers are working to identify biomarkers to detect a person’s chances of developing colon cancer. Much like blood pressure and cholesterol tests can indicate heart disease risk, researchers here hope that some day the makeup of blood and urine will be able to tell who’s at risk for colorectal cancer, why they may be at risk and what they can do to reduce their risk.

Postdoctoral fellows Joy Owen and Veronika Fedirko examine samples in Robin Bostick’s lab at the Winship Cancer Institute of Emory University.

For now, the Emory study team is analyzing the rectal tissue samples of people with colon adenomatous polyps, non-cancerous growths considered precursors to colon cancer, and comparing them to rectal tissue samples from people who don’t have polyps. They’re also looking at whether the differences they detect in rectal tissue can also be found in blood or urine. Currently, no accepted tests exist to determine whether someone may be at risk for colon cancer.

“Most people would rather provide a blood or urine sample than get a rectal biopsy,” says Robin Bostick, MD, MPH, Rollins School of Public Health epidemiology professor and study principal investigator. Bostick is also a clinical faculty member at the Winship Cancer Institute at Emory and a Georgia Cancer Coalition Distinguished Cancer Scholar.

Read more

Posted on by adobbs in Cancer 1 Comment

Looking at simple foods to protect against breast cancer

Researchers at the Winship Cancer Institute of Emory University have found that the hormone adiponectin may reduce the ability of cancer cells to migrate from the breast and invade other tissues. Adiponectin appears to protect against the effects of obesity on metabolism, the heart and blood vessels, the researchers say.

Fat cells make up most of the breast tissue, and some of the hormones produced by fat cells can have tumor-stimulating effects. Previous studies have shown that women with high body mass index (highest fifth) have double the death rate from breast cancer compared to those in the lowest fifth.

Dipali Sharma, PhD

The key to translating this research for patient care lies in finding a way to increase a person’s adiponectin, says Dipali Sharma, PhD, assistant professor of hematology and medical oncology at Winship.

Currently, Winship scientists are testing a molecule found in certain foods that appears to mimic the effects of adiponectin. The molecule is found in grapes, cabbage and green tea.

Read more

Posted on by Vince Dollard in Cancer Leave a comment