U of S researcher to look at role of metals in multiple sclerosis

Tackling drug-resistant cancer

Colleen MacPherson
December 2, 2011, 11:33 am

Troy Harkness. Photo by Colleen MacPherson

Using chemotherapy to kill breast cancer cells is one thing; eradicating drug-resistant cells is a whole other challenge, but one U of S researcher in the College of Medicine thinks he is onto a treatment protocol that holds exciting potential for those with breast cancer and other forms of cancer as well. 

In the lab of Troy Harkness, associate professor in the Department of Anatomy and Cell Biology, research into combining chemo drugs with an unexpected partner—a drug commonly used to treat diabetes—is showing positive results in killing drug-resistant cancer cells. It is work that the Canadian Breast Cancer Foundation (CBCF) has recognized and will fund for the next three years.

Explaining his work in the simplest possible terms, Harkness said the key seems to be in restoring the health of the cell’s chromosomes, which then allows the cell to either repair itself or destroy itself rather than continue to replicate as a cancer cell. “That’s the hypothesis we’re working on.”

His work in this area goes back a number of years to Harkness using chemotherapy treatment on cells to observe the development of drug resistance. “We would treat the cells with a low-dose drug which would kill most of them, but there were some that weren’t killed. We’d ramp up the dose and watch what happened to those cells. Many survived quite nicely and would become resistant to other drugs as well.” Harkness suspected damage to chromosomes “created the opportunity for drug resistance. The question we asked was whether reversing that damage would help kill drug-resistant cells.”

During those studies, data from other labs appeared indicating people being treated for type 2 diabetes display a reduced incidence of some cancers. Harkness introduced a common anti-diabetic drug along with the chemotherapy drugs and the results were exciting—this co-treatment protocol killed the drug-resistant cancer cells. The anti-diabetic drug appeared to improve the health of the chromosomes, reduce the cell’s defences and allow the chemo drug to do its work, all without damaging healthy cells.

Expanding his work to drug-resistant human leukemia and breast cancer cells, and rat brain cancer cells, Harkness got the same results. “We wondered if there is an effective way to treat all drug-resistant cancer cells,” he said.

With $125,000 a year for the next three years from the CBCF, Harkness’ lab will continue to explore how anti-diabetic drugs protect patients from multiple drug-resistant breast cancer, and possibly drug-resistant cells in all forms of cancer. “In three years, we expect to have a pretty good idea of what the drugs are doing to chromosomes to help the cell behave better, and to understand the pathways within the cells that mediate this protective mechanism. It’s information that will help clinicians and other researchers make more informed choices about treatment.”

Asked about elevating his research to animal trials, Harkness admitted it is not his area of specialty—“my best approach is to collaborate,” adding a research group in Singapore is interested in applying his drug protocol to mice.

Harkness is modest about the significance of his work. “It’s small steps, and this is a long-term investment. There’s still so much to learn about the cell, even in its healthy state. People thought we’d have all the answers when they mapped the human genome but that just created another level of complexity. Every time you think you’ve got something solved, you open another door and ‘Oh oh, no you don’t.’

“Once you start to see how a cell works, all the moving parts, you see how many things can go wrong. Any one of those things can cause the cell to grow out of control, and that’s cancer.”

While the number of questions yet to be answered about the cell may be daunting, Harkness said every day in the lab is exciting. “This is what we love to do,” adding that everyone in his lab—research associates, research assistants, grad students, even the computer experts who crunch his research data—recognize “that finding a cure for cancer is going to take a long time and is beyond the capabilities of a single lab.” It’s about many small steps adding up to significant progress, and about bringing hope to cancer sufferers “by them knowing that someone out there is working on this.”

http://news.usask.ca/2011/12/02/tackling-drug-resistant-cancer/

U of S study of an ancient bacterial gene sheds light on movement of North American peoples

Posted February 16, 2011

FOR IMMEDIATE RELEASE – Feb. 16, 2011
2011-02-07-OTHER

DNA from the stomach bacteria of a young man who died hundreds of years ago is shedding light on movement patterns of North American peoples and when they came in contact with Europeans.

Treena Swanston

University of Saskatchewan researcher Treena Swanston worked with Helicobacter pylori DNA amplified from the stomach tissue of a young man who died between 340 and 160 years ago on a glacier high in the mountains of Tatshenshini-Alsek Park in British Columbia.

Members of the Champagne and Aishihik First Nations, on whose traditional lands he was found, named the site Kwäday Dän Ts'ìnchi, or “Long Ago Person Found.” The individual is estimated to have been 18 or 19 years old when he died. Swanston’s work was undertaken in collaboration with these First Nations.

H. pylori is a common stomach bacteria, present in about half of all people. High levels of H. pylori infections have been identified in the circumpolar region, and Canadian aboriginal communities have been identified by a Canadian Helicobacter study group as a population with the highest risk of developing a Helicobacter-related disease such as stomach ulcers. (An autopsy of the Kwäday Dän Ts'ìnchi individual revealed no sign of this problem.)

Swanston’s analysis of the ancient H. pylori DNA revealed that some of the DNA sequences from its vacA gene are similar to previously published novel sequences associated with Alaskan strains. These are in turn closely related to vacA sequences in Asian strains. This suggests the bacteria travelled with the ancestors of the Kwäday Dän Ts'ìnchi individual as they migrated from Asia to the New World thousands of years ago.

However, Swanston found that some of the ancient H. pylori vacA sequences were similar to sequences in European strains, suggesting European contact.

While DNA from ancient H. pylori has been amplified once before, this is the first time that an ancient H. pylori strain was characterized based on vacA sequence data. Swanston’s work adds to the current research on ancient human migrations, and when different groups came into contact with one another.

Swanston is a post-doctoral fellow in the U of S Department of Anatomy and Cell Biology (College of Medicine) and a sessional instructor in the Department of Archaeology and Anthropology (College of Arts and Science).

The complete research article, entitled “The Characterization of Helicobacter pylori DNA Associated with Ancient Human Remains Recovered from a Canadian Glacier,” will be published online February 16 at the Public Library of Science (PLoS ONE) at http://dx.plos.org/10.1371/journal.pone.0016864.

-30-

For more information, contact:

Girl's lifesaving surgeon sets up in city