Tracing the start of COVID-19 in GA

At a time when COVID-19 appears to be receding in much of Georgia, it’s worth revisiting the start of the pandemic in early 2020. Emory virologist Anne Piantadosi and colleagues have a paper in Viral Evolution on the earliest SARS-CoV-2 genetic sequences detected in Georgia. Analyzing relationships between those virus sequences and samples from other states and countries can give us an idea about where the first COVID-19 infections in Georgia came from. We can draw Read more

Reddit as window into opioid withdrawal strategies

Drug abuse researchers are using the social media site Reddit as a window into the experiences of people living with opioid addiction. Abeed Sarker in Emory's Department of Biomedical Informatics has a paper in Clinical Toxicology focusing on the phenomenon of “precipitated withdrawal,” in collaboration with emergency medicine specialists from Penn, Rutgers and Mt Sinai. Precipitated withdrawal is a more intense form of withdrawal that can occur when someone who was using opioids starts medication-assisted treatment Read more

CROI: HIV cure report and ongoing research

The big news out of CROI (Conference on Retroviruses and Opportunistic Infections) was a report of a third person being cured of HIV infection, this time using umbilical cord blood for a hematopoetic stem cell transplant. Emory’s Carlos del Rio gave a nice overview of the achievement for NPR this morning. As del Rio explains, the field of HIV cure research took off over the last decade after Timothy Brown, known as “the Berlin patient,” Read more

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Invasive lung cancer cells have distinct roles

When cancer cells split off from a tumor to seed deadly metastases, they are thought to travel as clusters or packs, a phenomenon known as collective invasion. The members of an invasive pack are not all alike, scientists at Winship Cancer Institute of Emory University have learned.

Lung cancer cells making up an invasive pack have specialized roles as leaders and followers, which depend on each other for mobility and survival, the scientists report in Nature Communications.

The differences between leaders and followers — and their interdependence — could be keys for future treatments aimed at impairing or preventing cancer metastasis, says senior author Adam Marcus, PhD, associate professor of hematology and medical oncology at Winship Cancer Institute and Emory University School of Medicine.

“We’re finding that leader and follower cells have a symbiotic relationship and depend on each for survival and invasion,” he says. “Because metastatic invasion is the deadliest aspect of cancer, our goal is to find agents that disrupt that symbiotic relationship.”

Marcus and former graduate student Jessica Konen, PhD began by observing how a mass of lung cancer cells behaves when embedded in a 3-D protein gel. The cells generally stick together, but occasionally, a few cells extend out of the mass like tentacles, with the leader cell at the tip.

“We saw that when the leader cell became detached or died unexpectedly, the followers could no longer move,” says Konen, now a postdoctoral fellow at MD Anderson. “In one particular movie, we saw a leader cell come out away from the rest of the cells, and then seem to realize that nobody was following him. He actually did a 180, and went back to grab cells to bring with him.” Read more

Posted on by Quinn Eastman in Cancer 1 Comment

Blocking glioblastoma escape

Treatment strategies for several types of cancer have been transformed by the discovery of “targeted therapies,” drugs directed specifically against the genetic mutations that drive tumor growth. So far, these strategies have been relatively unsuccessful when it comes to glioblastoma, the most common and most deadly form of brain tumor affecting adults. Glioblastoma was one of the first tumor types to be analyzed in the Cancer Genome Atlas mega-project, but many of the molecular features of glioblastoma have been difficult to exploit.

For example, about 40 percent of glioblastoma tumors ray ban baratas have extra copies of the EGFR (epidermal growth factor receptor) gene. EGFR provides a pedal-to-the-metal growth signal and is known to play a role in driving the growth of lung and colon cancers as well. But drugs targeted against EGFR that have extended patient survival in lung cancer have shown disappointing results with glioblastoma. The reason: the tumor cells can quickly mutate the EGFR gene or switch to reliance on other growth signals.

Keqiang Ye, PhD and colleagues recently described the discovery of a compound that may be valuable in fighting glioblastoma. The Emory researchers devised a scheme to stop tumor cells from using well-known escape routes to avoid EGFR-based drugs. Their results are published in the journal Science Signaling. Postdoctoral fellow Kunyan He, PhD, is the first author.

The compound they identified inhibits the enzyme JAK2, one of the apparent escape Ray Ban outlet routes taken by glioblastoma cells. The compound can pass the blood-brain barrier and inhibit glioblastoma growth while having low toxicity, the researchers report.

Posted on by Quinn Eastman in Cancer 1 Comment

Dye me anticancer yellow

Over the last few years, pathologist Keqiang Ye and his colleagues have displayed an uncanny talent for finding potentially useful medicinal compounds. Recently another example of this talent appeared in Journal of Biological Chemistry.

Keqiang Ye, PhD

Postdoctoral fellow Qi Qi is first author on the paper. Collaborators include Jeffrey Olson, Liya Wang, Hui Mao, Haian Fu, Suresh Ramalingam and Shi-Yong Sun at Emory and Paul Mischel at UCLA.

Qi and Ye were looking for compounds that could inhibit the growth of an especially aggressive form of brain cancer, glioblastoma with deletion in the tumor suppressor gene PTEN. Tumors with this deletion do not respond to currently available targeted therapies.

The researchers found that acridine yellow G, a fluorescent dye used to stain microscope slides, can inhibit the growth of this tumor:

Oral administration of this compound evidently decreases the tumor volumes in both subcutaneous and intracranial models and elongates the life span of brain tumor inoculated nude mice. It also displays potent antitumor effect against human lung cancers. Moreover, it significantly decreases cell proliferation and enhances apoptosis in tumors…

Optimization of this compound by improving its potency through medicinal chemistry modification might warrant a novel anticancer drug for malignant human cancers.

Ye’s team observed that acridine yellow G appears not to be toxic in rodents. However, the acridine family of compounds tends to intercalate (insert itself) into DNA and can promote DNA damage, so more toxicology studies are needed. Other acridine family compounds such as quinacrine have been used to treat bacterial infections and as antiinflammatory agents, they note.

A paramecium stained with acridine orange, which shows anticancer activity for tumors containing PTEN mutations

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