CANCER: Surveillance

Showing posts with label Surveillance. Show all posts

Tuesday, July 9, 2013

Previously Unknown Surveillance Mechanism Used By Cells To Monitor Oxidatively Damaged DNA

Main Category: Genetics
Also Included In: Alzheimer's / Dementia;??Cancer / Oncology;??Parkinson's Disease
Article Date: 18 Jun 2013 - 1:00 PDT Current ratings for:
Previously Unknown Surveillance Mechanism Used By Cells To Monitor Oxidatively Damaged DNA
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In current health lore, antioxidants are all the rage, as "everybody knows" that reducing the amount of "reactive oxygen species" -- cell-damaging molecules that are byproducts of cellular metabolism -- is critical to staying healthy. What everyone doesn't know is that our bodies already have a complex set of processes built into our cells that handle these harmful byproducts of living and repair the damage they cause.

For example, few of us realize that, while our cells' DNA is constantly being damaged by reactive oxygen species (as well as by other forces), there are also complex mechanisms that constantly assess that damage and make repairs to our fragile genetic material at least 10,000 times a day in every cell in our bodies. The vital biochemical processes by which this constant DNA repair takes place are still only partially understood because of their complexity, speed, and the difficulty of studying complex interactions within living cells. Moreover, it remains unknown how cells sense the oxidatively damaged DNA in the first place.

In an article published in the Proceedings of the National Academy of Sciences (PNAS) a research team from University of North Carolina at Charlotte announced that they had uncovered a previously unknown surveillance mechanism, known as a DNA damage checkpoint, used by cells to monitor oxidatively damaged DNA. The finding, first-authored by UNC Charlotte biology graduate student Jeremy Willis and undergraduate honors student Yogin Patel, was also co-authored by undergraduate honors student Barry L. Lentz and assistant professor of biology Shan Yan.

"DNA damage is the underlying pathology in many major human diseases, including cancers and neurodegenerative disorders such as Alzheimer's and Parkinson's, so arriving at a full understanding of the sophisticated mechanisms that cells usually employ to avoid such disastrous outcomes is important," Yan noted.

Two biochemical pathways, known as ATM-Chk2 and ATR-Chk1, govern the cell's response and repair of double-strand DNA breaks and other types of DNA damage or replication stress respectively. The molecular mechanisms underlying the ATR-Chk1 checkpoint activation include the uncoupling of DNA helicase and polymerase activities and DNA end resection of double-strand breaks.

"The significance of what we have found is that there is a third, previously unknown trigger for ATR-Chk1 checkpoint pathway, and this novel mechanism is discovered in the context of oxidative stress," Yan said.

In particular, Yan's team discovered that under conditions of oxidative stress (in the presence of hydrogen peroxide) a base excision repair protein known as APE2 plays unexpected roles in the checkpoint response: single-strand DNA generation and Chk1 association. The protein was previously known to be involved in the DNA repair of oxidative damage, but not to extent revealed in the study's findings. The distinct role of APE2 in the single-strand DNA generation in 3' to 5' direction is referred to as single-strand break end resection ("SSB end resection") by the authors.

The study involved experiments performed with Xenopus laves (the African clawed frog, a species commonly used as a lab animal) egg extracts - an experimental system that Yan's lab has developed for studying DNA repair and checkpoint mechanisms in a cell-free conditions. Xenopus is useful because it is a vertebrate (and thus quite similar to humans in cell biology), and its egg cells can be easily produced and manipulated.

Yan is hopeful that this research will open new avenues to pharmacological strategies in drug development for cancer and neurodegenerative diseases.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our genetics section for the latest news on this subject. The article appeared in the June 10, 2013 print edition of PNAS: http://www.pnas.org/content/early/2013/06/06/1301445110.abstract.
The Yan laboratory at UNC Charlotte is funded in part by the University of North Carolina at Charlotte and a National Institute of General Medical Sciences/National Institutes of Health grant, number R15GM101571.
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Friday, May 31, 2013

Early Stage Testicular Cancer - Surveillance Is Best Follow-Up Strategy

Editor's Choice
Academic Journal
Main Category: Urology / Nephrology
Also Included In: Cancer / Oncology
Article Date: 17 May 2013 - 0:00 PDT Current ratings for:
Early Stage Testicular Cancer - Surveillance Is Best Follow-Up Strategy
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A long-term study of men with stage I seminoma, a common form of testicular cancer, suggests that surveillance for cancer recurrence, rather than additional chemotherapy or radiation therapy, is sufficient for the vast majority of patients who have undergone successful surgery for their cancer.

In a new long-term study conducted in Denmark, researchers analyzed a national clinical database and found that 99.6% of patients who only underwent surveillance (following a successful surgery) were alive after 10 years of being diagnosed with testicular cancer.

Surveillance means carrying out routine CT scans, physical exams, chest X-ray exams, and blood tests for a period of five years after surgery.

In some countries, such as Denmark (where the study took place), the preferred follow-up strategy is surveillance alone. In the U.S. half of patients undergo either radiotherapy or chemotherapy as follow-up treatment, while the other half only receive surveillance.

There has been a recent increase in the number of patients undergoing surveillance alone in the U.S., a trend that will likely continue following this new finding.

Treatment options such as chemotherapy or radiotherapy can cause very harmful side effects, including a higher risk of secondary cancers (such as leukemia). Therefore, other follow-up strategies that don't incur such drastic risks, such as surveillance alone, are preferred.

Mette Sakso Mortensen, MD, a PhD student at the Department of oncology at the Copenhagen University Hospital in Copenhagen, Denmark, said:

"To our knowledge, this study is the largest to address this issue in patients with stage I seminoma, and with the longest follow-up. Now we have solid proof that surveillance is safe and appropriate for most patients with this particular cancer.
We also characterized key prognostic factors for relapse, which can help us identify high-risk patients who may need adjuvant therapy instead of surveillance. However, in general, seminoma stage I patients can safely be followed on a surveillance program."

A total of 1,822 men with stage I seminoma, who underwent successful surgery were followed on a five year surveillance program. The researchers were able to follow the patients for an average of 15.4 years.

19.5 percent of the patients experienced a relapse, of whom 216 received radiotherapy while 136 received chemotherapy and only 3 underwent surgery.

The 10-year-cancer-specific survival rate was 99.6 percent, which translates into four men dying out of every 1,000 who underwent surveillance alone.

The risk of relapse increased among patients whose tumor size was bigger than 1.5 inches and spread to lymphatic vessels or blood, as well as those whose levels of a blood marker called human chorionic gonadotropin were high.

Even though testicular cancer is quite rare among the general population, it is the most common solid tumor among young men. Approximately 4,000 people will be diagnosed with stage I seminoma this year in the U.S.

ASCO President-Elect Clifford A. Hudis, MD, said:

"This important study is one of several recent reminders that sometimes "less is more? in patient care. Opting for surveillance spares patients, most of whom are young men, from the harmful side effects of chemotherapy and radiation without diminishing their chances for a long and healthy life."

Scientists at UC Davis found that frequent CT scanning for testicular cancer surveillance was associated with secondary malignancies.

Written by Joseph Nordqvist
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

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