Featured Research

from universities, journals, and other organizations

Achilles' Heel Of Pancreatic Cancer Discovered

Date:
November 7, 2008
Source:
University of California - Davis - Health System
Summary:
Researchers have discovered a metabolic deficiency in pancreatic cancer cells that can be used to slow the progress of the deadliest of all cancers.

UC Davis Cancer Center researchers have discovered a metabolic deficiency in pancreatic cancer cells that can be used to slow the progress of the deadliest of all cancers.

Published in the October issue of the International Journal of Cancer, study results indicate that pancreatic cancer cells cannot produce the amino acid arginine, which plays an essential role in cell division, immune function and hormone regulation. By depleting arginine levels in cell cultures and animal models, the team was able to significantly reduce pancreatic cancer-cell proliferation.

"There have been few significant advances in 15 years of testing available chemotherapy to treat pancreatic cancer," said Richard Bold, chief of surgical oncology at UC Davis and senior author of the study. "The lack of progress is particularly frustrating because most patients are diagnosed after the disease has spread to other organs, eliminating surgery as an option. We have to turn back to basic science to come up with new treatments."

Bold explained that average survival time for those diagnosed with pancreatic cancer is just four-and-a-half months, although chemotherapy can extend that prognosis up to six months.

"There is a dire need to find new options for these patients. While our findings do not suggest a cure for pancreatic cancer, they do promise a possible way to extend the life expectancies of those diagnosed with it," Bold said.

Bold and his colleagues hypothesized that pancreatic cancer cells lack the ability to produce arginine. In human pancreatic tumors, they measured levels of an enzyme — argininosuccinate synthetase — required to synthesize arginine.

The enzyme was not detected in 87 percent of the 47 tumor specimens examined, suggesting that the majority of pancreatic cancers require arginine for cell growth because of an inability to synthesize the amino acid.

The researchers then conducted further tests using pancreatic cell lines that represent the varying levels of argininosuccinate synthetase observed in human tumor specimens. Focusing on the lines with lowest levels, the researchers depleted arginine levels in cultures of pancreatic cell lines using arginine deiminase, an enzyme isolated from a Mycoplasma bacteria.

The enzyme was modified by adding polyethylene glycol chains to increase size and circulatory time.

The researchers found that exposing the pancreatic cancer cell lines to the modified arginine deiminase enzyme inhibited cancer-cell proliferation by 50 percent. They then treated mice bearing pancreatic tumors with the same compound and found an identical outcome: a 50 percent reduction in tumor growth. According to Bold, the current study represents a unique approach to cancer treatment in that it is one of the first to identify a metabolic pathway that can be leveraged to interrupt cancer growth.

"Instead of killing cells as with typical chemotherapy, we instead removed one of the key building blocks that cancer cells need to function," Bold said.

Metabolic interruptions like this one are also being studied for their potential in treating cancers of the blood, such as leukemia and lymphoma. In those cases, depleting the amino acid asparagine may be used in slowing cancer-cell growth.

Bold and his colleagues are continuing their laboratory work on the effects of arginine deprivation on pancreatic cancer. They will next be looking for ways to increase pancreatic cell sensitivity to arginine deprivation.

The researchers have also begun designing human clinical trials in cooperation with the manufacturer of arginine deiminase, Polaris Pharmaceuticals.

"We're looking at whether we can combine this treatment with certain kinds of chemotherapy," Bold said. "This additional research is needed to inform the clinical work and move it forward more quickly. The better we understand this process, the more we can use it in the fight against pancreatic cancer."

Additional study authors included Tawnya Bowles, Joseph Galante, Colin Parsons and Subbulakshmi Virudachalam of the UC Davis Department of Surgery; and Randie Kim and Hsing-Jien Kung of the UC Davis Department of Biochemistry and Molecular Medicine.

The study was funded by DesigneRxPharmacolgics of Vacaville, Calif.


Story Source:

The above story is based on materials provided by University of California - Davis - Health System. Note: Materials may be edited for content and length.


Cite This Page:

University of California - Davis - Health System. "Achilles' Heel Of Pancreatic Cancer Discovered." ScienceDaily. ScienceDaily, 7 November 2008. <www.sciencedaily.com/releases/2008/11/081106181417.htm>.
University of California - Davis - Health System. (2008, November 7). Achilles' Heel Of Pancreatic Cancer Discovered. ScienceDaily. Retrieved September 23, 2014 from www.sciencedaily.com/releases/2008/11/081106181417.htm
University of California - Davis - Health System. "Achilles' Heel Of Pancreatic Cancer Discovered." ScienceDaily. www.sciencedaily.com/releases/2008/11/081106181417.htm (accessed September 23, 2014).

Share This



More Health & Medicine News

Tuesday, September 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Costs Keep Mounting

Ebola Costs Keep Mounting

Reuters - Business Video Online (Sep. 23, 2014) The WHO has warned up to 20,000 people could be infected with Ebola over the next few weeks. As Sonia Legg reports, the implications for the West African countries suffering from the disease are huge. Video provided by Reuters
Powered by NewsLook.com
Ebola Cases Could Reach 1.4 Million Within 4 Months

Ebola Cases Could Reach 1.4 Million Within 4 Months

Newsy (Sep. 23, 2014) Health officials warn that without further intervention, the number of Ebola cases in Liberia and Sierra Leone could reach 1.4 million by January. Video provided by Newsy
Powered by NewsLook.com
WHO: Ebola Cases to Triple in Weeks Without Drastic Action

WHO: Ebola Cases to Triple in Weeks Without Drastic Action

AFP (Sep. 23, 2014) The number of Ebola infections will triple to 20,000 by November, soaring by thousands every week if efforts to stop the outbreak are not stepped up radically, the WHO warned in a study on Tuesday. Duration: 01:01 Video provided by AFP
Powered by NewsLook.com
5 Ways Men Can Prevent Most Heart Attacks

5 Ways Men Can Prevent Most Heart Attacks

Newsy (Sep. 23, 2014) No surprise here: A recent study says men can reduce their risk of heart attack by maintaining a healthy lifestyle, which includes daily exercise. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins