Category: cancer

CCRC-Franklin researchers target cancer stem cells

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A new paper by research scientists at the Complex Carbohydrate Research Center focuses on cancer stem cells:

the research team demonstrates that the sugar molecule, made by an enzyme known as GnT-V, regulates the development of a particular subset of cancerous cells known as cancer stem cells.

Much like normal stem cells that sustain organs and tissues, cancer stem cells can self-renew, and their cellular offspring clump together to form tumors. Conventional treatments like surgery, chemotherapy or radiation may reduce overall tumor size, but if they do not kill the cancer stem cells, the disease is likely to return.

"You can think of it like a colony of ants," said Michael Pierce, director of UGA's Cancer Center, Mudter Professor in Cancer Research in UGA's Complex Carbohydrate Research Center and principal investigator for the study. "You can kill the ants in the mound, but if you don't get the queen, they will come back."

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Their discovery paves the way for new cancer treatment methods specifically designed to inhibit GnT-V, which, when combined with other treatments, may help prevent disease recurrence.

While their study focused particularly on colorectal cancers, the researchers hope their discovery may one day work for a variety of cancer types.

"This is a rapidly growing field within the cancer research community," said Pierce, who is also a Distinguished Professor of Biochemistry and Molecular Biology in UGA's Franklin College of Arts and Sciences. "We want to know what makes these cancer stem cells unique and what we need to do in order to target them specifically so we can develop new treatments and save lives."

Great work by some of our best. Congratulations to Pierce and his team. Continued good results on this important work.

Chemistry researchers enhance chemotherapy with nanoparticles

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Dhar_Marrache_Pathak.jpgAs science moves forward, disease treatment regimes become more refined, safer and more effective. Great news from Shanta Dhar's research lab in the department of chemistry:

Dhar, assistant professor of chemistry in the UGA Franklin College of Arts and Sciences, and Rakesh Pathak, a postdoctoral researcher in Dhar's lab, constructed a modified version of cisplatin called Platin-M, which is designed to overcome this resistance by attacking mitochondria within cancerous cells. They published their findings recently in the Proceedings of the National Academy of Sciences.

"You can think of mitochondria as a kind of powerhouse for the cell, generating the energy it needs to grow and reproduce," said Dhar, a member of the UGA Cancer Center and principal investigator for the project. "This prodrug delivers cisplatin directly to the mitochondria in cancerous cells. Without that essential powerhouse, the cell cannot survive."

Sean Marrache, a graduate student in Dhar's lab, entrapped Platin-M in a specially designed nanoparticle 1,000 times finer than a human hair that seeks out the mitochondria and releases the drug. Once inside, Platin-M interferes with the mitochondria's DNA, triggering cell death.

Dhar's research team tested Platin-M on neuroblastoma-a cancer commonly diagnosed in children-that typically originates in the adrenal glands. In preliminary experiments using a cisplatin-resistant cell culture, Platin-M nanoparticles were 17 times more active than cisplatin alone.

Improving on current therapies can be a very difficult target. But with an expanding knowledge about the role of mitochondria in cell survival, drug design and delivery mechanism on the nanoscale have scientists poised for promising breakthroughs. Great work.

Image: Shanta Dhar (center), Rakesh Pathak (right) and Sean Marrache, courtesy of UGA Photographic Services.

Study deepens the connection between hypoxia and cancer growth

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There are a number of species that have a low to negligible probability of developing cancer. These include squirrels, turtles, the mole rat and certain whales. The reasons why are linked to these species' ability to adapt their oxygen demand when faced with a low oxygen supply. That connection itself goes back to a discover by the great physiologist and Nobel laureate Otto Warburg, who hypothesized in 1924 that, whatever the secondary causes of cancer, there is only one primary cause: a cell switch to fermentation of sugars in the face of low oxygen levels. The details of this fascinating story have now been filled in a little further by UGA bioinformatics and computational bioloy professor, Regents-GRA Eminent Scholar Ying Xu:

Chronic inflammation that induces low oxygen levels, or hypoxia, is a widely accepted cause of cancer development. However, the link between hypoxia and cell proliferation is far from clear.

A new study by University of Georgia researchers presents a model explaining the connection between chronic inflammation, low oxygen levels and the resulting cell proliferation that begins the cancer process.

"A switch in energy metabolism mechanisms—from the normal oxygenic respiration our cells use to process glucose into energy to a much less efficient, much lower capacity process called anaerobic fermentation—leads to glucose accumulation," said Ying Xu, a Regents-Georgia Research Alliance Eminent Scholar and professor of bioinformatics and computational biology in the UGA Franklin College of Arts and Sciences.

According to the study, this accumulation of glucose and related signaling through the body leads to a reaction much the same as to that of damaged tissue, eventually triggering the cell proliferation that causes cancer. Specifically it leads to synthesis, export and fragmentation of hyaluronic acids, which can serve as signals for tissue repair.

A fascinating and important breakthrough, in a field reluctant to use that term but where many desperately hope for its reality. Building on the work of the past, questioning current practices, explaining a complex process through the use of simple analogs - all the hallmarks of great research. The idea that cancer cell growth might be understood as a survival reaction, to a mistaken circumstance, in the body could not have wider significance. Great work and there's no doubt more to come from Xu and his team. 

New drug formulation for cancer treatment

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Shanta-Dhar.jpgGreat new research from the department of chemistry:

The drug dichloroacetate, or DCA, was touted as a cure-all, but after years of work, scientists are still searching for ways to make the unique treatment as effective as possible.

Now, researchers at the University of Georgia have discovered a new way to deliver this drug that may one day make it a viable treatment for numerous forms of cancer. They published their findings in the American Chemical Society's journal ACS Chemical Biology.

"DCA shows great promise as a potential cancer treatment, but the drug doesn't find and attack cancer cells very efficiently in the doses researchers are testing," said Shanta Dhar, an assistant professor of chemistry in the UGA Franklin College of Arts and Sciences. "We have developed a new compound based on DCA that is three orders of magnitude more potent than standard treatments."

Every cell in the body needs energy to divide and grow, and most of them do this by breaking down sugar. When cells misbehave, they are normally deprived of their food and die in a process called apoptosis.

Dhar is becoming one of the foremost cancer researchers in the country, and this new work (and accompanying technology) only re-emphasize that case. So very much goes into getting to the stage where we can promote published results from our faculty, and having the institutional pieces of the puzzle in place where our researchers can do their best work is where these real benefits to society can be glimpsed. Hard to overstate the implications of this new research, the product of great perserverence and dedication by Dr. Dhar and her team. And it's also occasion to remember how many things have to happen in concert to make it all possible.

Image: Shanta Dhar, with graduate assitant Sean Marrache, in her lab.

Discovery about little-studied protein holds promise for drug treatments

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More evidence that the front lines of research on life-threatening diseases are right here on the UGA campus and in the Franklin College. Insightful new work from a research group lead by faculty member Natarajan Kannan of the Institute for Bioinformatics and the department of biochemistry and molecular biology:

Enter protein kinases. Like specialized traffic signals, this huge class of proteins is critical for many aspects of cell communication, telling them when to begin work and when to stop.

Now, University of Georgia researchers have discovered that a little-studied part of the protein kinases that once appeared non-functional may actually control the most critical functions of the entire molecule. Their research promises to help improve drugs used to fight a variety of life-threatening diseases, from diabetes to cancer.

"The overall goal of this project was to better understand how these proteins function and what mechanisms control their function," said Natarajan Kannan, a Georgia Cancer Coalition Distinguished Scholar and assistant professor of biochemistry and molecular biology in the Franklin College of Arts and Sciences. "Our research shows that these little-studied dark regions of the protein are directly affecting the molecule's function."

$4.1 million from NIH to UGA researchers

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More terrific news from Franklin College scientists in the CCRC:

Ovarian and pancreatic cancers are among the most deadly, not because they are impossible to cure, but because they are difficult to find. There are no screening tests that can reliably detect their presence in early stages, and most diagnoses are made after the disease has already spread to lymph nodes and vital organs.

But University of Georgia cancer researchers Karen Abbott and Michael Pierce are exploring new methods of detecting these silent killers using the most advanced technologies available. They recently received two, five-year grants from the National Institutes of Health totaling more than $4.1 million to support their projects. Their work promises to help find the cancers early, when doctors have the best chance to help their patients fight the disease.

"Almost every cancer can be successfully treated if it is diagnosed early enough," said Pierce, Distinguished Research Professor in the Franklin College of Arts and Sciences and director of the UGA Cancer Center. "If we and others can identify something that helps us find the cancer very early, we will save lives."

New study links hypoxia to cancer growth

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A research team led by Ying Xu, Regents-Georgia Research Alliance Eminent Scholar and professor of bioinformatics and computational biology in the Franklin College, has published some compeeling new findings on the growth of cancer cells:

Low oxygen levels in cells may be a primary cause of uncontrollable tumor growth in some cancers, according to a new University of Georgia study. The authors' findings run counter to widely accepted beliefs that genetic mutations are responsible for cancer growth.

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The research team analyzed samples of messenger RNA data-also called transcriptomic data-from seven different cancer types in a publicly available database. They found that long-term lack of oxygen in cells may be a key driver of cancer growth. The study was published in the early online edition of the Journal of Molecular Cell Biology.

UGA scientists move closer to breast cancer vaccine

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Work by researchers from Franklin College and the Mayo Clinic in Arizona is being widely reported:

Researchers from the University of Georgia and the Mayo Clinic in Arizona have developed a vaccine that dramatically reduces tumors in a mouse model that mimics 90 percent of human breast and pancreatic cancer cases—including those resistant to common treatments.