Two items relevant to long COVID

One of the tricky issues in studying in long COVID is: how widely do researchers cast their net? Initial reports acknowledged that people who were hospitalized and in intensive care may take a while to get back on their feet. But the number of people who had SARS-CoV-2 infections and were NOT hospitalized, yet experienced lingering symptoms, may be greater. A recent report from the United Kingdom, published in PLOS Medicine, studied more than Read more

All your environmental chemicals belong in the exposome

Emory team wanted to develop a standard low-volume approach that would avoid multiple processing steps, which can lead to loss of material, variable recovery, and the potential for Read more

Signature of success for an HIV vaccine?

Efforts to produce a vaccine against HIV/AIDS have been sustained for more than a decade by a single, modest success: the RV144 clinical trial in Thailand, whose results were reported in 2009. Now Emory, Harvard and Case Western Reserve scientists have identified a gene activity signature that may explain why the vaccine regimen in the RV144 study was protective in some individuals, while other HIV vaccine studies were not successful. The researchers think that this signature, Read more

Department of Hematology and Medical Oncology

Precision medicine with multiple myeloma

“Precision medicine” is an anti-cancer treatment strategy in which doctors use genetic or other tests to identify vulnerabilities in an individual’s cancer subtype.

Winship Cancer Institute researchers have been figuring out how to apply this strategy to multiple myeloma, with respect to one promising drug called venetoclax, in a way that can benefit the most patients.

Known commercially as Venclexta, venetoclax is already FDA-approved for some forms of leukemia and lymphoma. Researchers had observed that multiple myeloma cells with one type of chromosomal DNA rearrangement tend to be sensitive to venetoclax. About 20 percent of multiple myelomas carry this rearrangement, called t(11;14).

“One of our main goals is to identify a better biomarker to predict patient response to venetoclax,” says Winship researcher Vikas Gupta, lead author of a paper published in Blood earlier this year.

Vikas Gupta, MD, PhD

Gupta works together with Winship hematologist Jonathan Kaufman and researcher Larry Boise, also associate director for education and training, to translate insights about myeloma cells into advances for patient care.

In a recent clinical trial led by Kaufman, a sizable fraction of people whose myelomas carried the t(11;14) rearrangement responded well to venetoclax, when their cancers were already refractory to other drugs. Another study that did not separate out myelomas with t(11;14) extended progression-free survival by almost a year.

However, venetoclax also was associated with increased mortality from infections, which led the FDA in 2019 to put the second study on hold temporarily. Other ongoing studies of venetoclax with multiple myeloma were affected.  It highlights the need to predict which patients would benefit from venetoclax – and which would not be likely to, for whom the drug may pose more risk.

In their paper, Winship investigators discovered that a set of cell markers predicted sensitivity to venetoclax better than t(11;14). These were markers for B cells, a type of white blood cell related to both multiple myeloma and some of the other forms of leukemia and lymphoma venetoclax is used to treat.

Gupta says that it was already possible to obtain myeloma cells from patients and test whether they are sensitive to venetoclax directly in the laboratory. But this isn’t practical for most clinics in cancer centers elsewhere.

“In contrast, the B cell phenotype can easily be assessed by flow cytometry, a technique that is routinely performed in clinical labs,” Gupta says. “So we are attempting to refine and validate our panel of flow cytometry markers, so that it can be used to easily and accurately predict which patients are sensitive to venetoclax.”

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Posted on by Quinn Eastman in Cancer 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

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

Anticancer drug strategy: making cells choke on copper

What do cancer cells have in common with horseshoe crabs and Mr. Spock from Star Trek?

They all depend upon copper. Horseshoe crabs have blue blood because they use copper to transport oxygen in their blood instead of iron (hemocyanin vs hemoglobin). Vulcans’ blood was supposed to be green, for the same reason.

Horseshoe Crab (Limulus polyphemus)

Horseshoe crabs and Vulcans use copper to transport oxygen in their blood. Cancer cells seem to need the metal more than other cells.

To be sure, all our cells need copper. Many human enzymes use the metal to catalyze important reactions, but cancer cells seem to need it more than healthy cells. Manipulating the body’s flow of copper is emerging as an anticancer drug strategy.

A team of scientists from University of Chicago, Emory and Shanghai have developed compounds that interfere with copper transport inside cells. These compounds inhibit the growth of several types of cancer cells, with minimal effects on the growth of non-cancerous cells, the researchers report in Nature Chemistry.

“We’re taking a tactic that’s different from other approaches. These compounds actually cause copper to accumulate inside cells,” says co-senior author Jing Chen, PhD, professor of hematology and medical oncology at Emory University School of Medicine and Winship Cancer Institute. Read more

Posted on by Quinn Eastman in Cancer Leave a comment