 |
|
UNC study supports role of circadian clock in response to chemotherapy
January 13, 2009CHAPEL HILL - For years, research has hinted that the time of day that cancer patients receive chemotherapy can impact their chances of survival. But the lack of a clear scientific explanation for this finding has kept clinicians from considering timing as a factor in treatment.
Now, a new study from the University of North Carolina at Chapel Hill has suggested that treatment is most effective at certain times of day because that is when a particular enzyme system - one that can reverse the actions of chemotherapeutic drugs - is at its lowest levels in the body.
The study, performed in mice, could also have implications for the prevention of new cancers.
The enzyme system implicated - called nucleotide excision repair- repairs many types of DNA damage that come not just from chemotherapy but also from the ultraviolet rays of the sun. Thus, by understanding the cyclical nature of this system, physicians may be able to pinpoint when it is most crucial for people to protect themselves from sun exposure to minimize their risk of skin cancer.
"Timing is everything, and here we have molecular data showing why this is especially true with regard to cancer," said senior study author Aziz Sancar, M.D., Ph.D., a member of the UNC Lineberger Comprehensive Cancer Center and Sarah Graham Kenan professor of biochemistry and biophysics in the UNC School of Medicine. Sancar is also a member of the National Academy of Sciences and the Turkish Academy of Sciences. "By hitting cancer cells with chemo at a time when their ability to repair themselves is minimal, you should be able to maximize effectiveness and minimize side effects of treatment."
The study, set to appear this week in the online early edition of the Proceedings of the National Academy of Sciences, provides the first solid evidence that the daily oscillations of the cell's repair machinery can affect the potency of cancer drugs.
The primary driver of this oscillatory behavior is the circadian clock, which keeps the biochemical, behavioral and physiological processes of many organisms, including mice and humans, on a 24-hour cycle. Every single cell in the body - whether from the kidney, liver or heart - has its own internal clock, and each of these are synchronized and coordinated by one master clock, located in a particular cluster of neurons in the brain.
Because of the important role that the circadian clock plays in regulating the daily rhythms of life, Sancar wanted to see what influence it had on important functions in the body, in particular the repair of damage to DNA caused by chemotherapy or UV radiation. This damage is usually repaired by a process called nucleotide excision repair, which cuts out and replaces sections of damaged DNA.
Sancar and his colleagues studied the behavior of the repair machinery in cerebrum or brain tissue of mice over the course of a day, and found that the ability to repair damage was at a minimum in the early morning and reached a maximum in the evening hours. They then looked at each of the six components that make up the repair machinery and found that the levels of one of them - the enzyme XPA - rose and fell in synchrony with the oscillations of the circadian clock. Thus, the researchers demonstrated that the cell's ability to repair damage is linked to the circadian clock, and that this daily oscillation is ultimately due to changes in the levels of one particular enzyme at different times of day.
Sancar now wants to extend these studies to determine whether the same cyclical changes in repair activity seen in mouse brain can also be observed in mouse testis. This avenue is particularly relevant because cisplatin - a chemotherapeutic agent commonly used to treat testicular cancer - kills cancer cells by damaging DNA.
While cisplatin is considered by many people to be a miracle drug - it completely cured Lance Armstrong - one in ten patients who take it still do not survive and it is not as effective on other cancers, such as colon, ovarian and lung cancers. Sancar said he believes that identifying the times when the cancer cells' ability to repair damage is at a minimum may enable clinicians to tailor treatment and improve the survival rate for people with testicular cancer and these other more common cancers as well.
He also would like to see his findings being used for cancer prevention. Because the enzyme Sancar identified also repairs damage caused by sunlight, he plans to determine if the repair capacity in human skin changes as a function of the time of day.
"If we show the same patterns in humans as we did in mice, then it could tell us when would be the safest time to be in the sun (2 p.m. to 6 p.m.), and when would be the best time to avoid sun exposure (6 a.m. to 10 a.m.)," Sancar said. "The new information could help us prevent skin cancers."
University of North Carolina School of Medicine
The enzyme system implicated - called nucleotide excision repair- repairs many types of DNA damage that come not just from chemotherapy but also from the ultraviolet rays of the sun. Thus, by understanding the cyclical nature of this system, physicians may be able to pinpoint when it is most crucial for people to protect themselves from sun exposure to minimize their risk of skin cancer.
"Timing is everything, and here we have molecular data showing why this is especially true with regard to cancer," said senior study author Aziz Sancar, M.D., Ph.D., a member of the UNC Lineberger Comprehensive Cancer Center and Sarah Graham Kenan professor of biochemistry and biophysics in the UNC School of Medicine. Sancar is also a member of the National Academy of Sciences and the Turkish Academy of Sciences. "By hitting cancer cells with chemo at a time when their ability to repair themselves is minimal, you should be able to maximize effectiveness and minimize side effects of treatment."
The study, set to appear this week in the online early edition of the Proceedings of the National Academy of Sciences, provides the first solid evidence that the daily oscillations of the cell's repair machinery can affect the potency of cancer drugs.
The primary driver of this oscillatory behavior is the circadian clock, which keeps the biochemical, behavioral and physiological processes of many organisms, including mice and humans, on a 24-hour cycle. Every single cell in the body - whether from the kidney, liver or heart - has its own internal clock, and each of these are synchronized and coordinated by one master clock, located in a particular cluster of neurons in the brain.
Because of the important role that the circadian clock plays in regulating the daily rhythms of life, Sancar wanted to see what influence it had on important functions in the body, in particular the repair of damage to DNA caused by chemotherapy or UV radiation. This damage is usually repaired by a process called nucleotide excision repair, which cuts out and replaces sections of damaged DNA.
Sancar and his colleagues studied the behavior of the repair machinery in cerebrum or brain tissue of mice over the course of a day, and found that the ability to repair damage was at a minimum in the early morning and reached a maximum in the evening hours. They then looked at each of the six components that make up the repair machinery and found that the levels of one of them - the enzyme XPA - rose and fell in synchrony with the oscillations of the circadian clock. Thus, the researchers demonstrated that the cell's ability to repair damage is linked to the circadian clock, and that this daily oscillation is ultimately due to changes in the levels of one particular enzyme at different times of day.
Sancar now wants to extend these studies to determine whether the same cyclical changes in repair activity seen in mouse brain can also be observed in mouse testis. This avenue is particularly relevant because cisplatin - a chemotherapeutic agent commonly used to treat testicular cancer - kills cancer cells by damaging DNA.
While cisplatin is considered by many people to be a miracle drug - it completely cured Lance Armstrong - one in ten patients who take it still do not survive and it is not as effective on other cancers, such as colon, ovarian and lung cancers. Sancar said he believes that identifying the times when the cancer cells' ability to repair damage is at a minimum may enable clinicians to tailor treatment and improve the survival rate for people with testicular cancer and these other more common cancers as well.
He also would like to see his findings being used for cancer prevention. Because the enzyme Sancar identified also repairs damage caused by sunlight, he plans to determine if the repair capacity in human skin changes as a function of the time of day.
"If we show the same patterns in humans as we did in mice, then it could tell us when would be the safest time to be in the sun (2 p.m. to 6 p.m.), and when would be the best time to avoid sun exposure (6 a.m. to 10 a.m.)," Sancar said. "The new information could help us prevent skin cancers."
University of North Carolina School of Medicine
Chemotherapy Current Events and Chemotherapy News RSSFertility procedures need not delay breast cancer treatment for younger women
A new study published in the November issue of the Journal of the American College of Surgeons shows that breast cancer patients under 40 years old who undergo fertility preservation do not face a significant delay in the treatment of their disease when their care is coordinated in a timely fashion.
Drugs to treat anemia in cancer patients linked to thromboembolism
Medications frequently given to cancer patients to reduce their risk of anemia are associated with an increased risk of deep vein thrombosis or pulmonary embolism, according to new research led by Dawn Hershman, M.D, M.S., co-director of the breast cancer program at the Herbert Irving Comprehensive Cancer Center at NewYork-Presbyterian Hospital/Columbia University Medical Center.
For young boys with cancer, testicular tissue banking may be option to preserve fertility
For parents of children with cancer, the hopeful news is that pediatric survival rates have steadily improved for decades. Among the bad news-treatments that enable survival often cause infertility.
FDA approved leukemia drugs shows promise in ovarian cancer cells
The drug Sprycel, approved for use by the U.S. Food and Drug Administration in patients with chronic myeloid leukemia, significantly inhibited the growth and invasiveness of ovarian cancer cells and also promoted their death, a study by researchers with UCLA's Jonsson Comprehensive Cancer Center found.
1930s drug slows tumor growth
Drugs sometimes have beneficial side effects. A glaucoma treatment causes luscious eyelashes. A blood pressure drug also aids those with a rare genetic disease.
First use of antibody and stem cell transplantation to successfully treat advanced leukemia
For the first time, researchers at Fred Hutchinson Cancer Research Center have reported the use of a radiolabeled antibody to deliver targeted doses of radiation, followed by a stem cell transplant, to successfully treat a group of leukemia and pre-leukemia patients for whom there previously had been no other curative treatment options.
New Synthetic Molecules Trigger Immune Response to HIV and Prostate Cancer
Researchers at Yale University have developed synthetic molecules capable of enhancing the body's immune response to HIV and HIV-infected cells, as well as to prostate cancer cells. Their findings, published online in the Journal of the American Chemical Society, could lead to novel therapeutic approaches for these diseases.
Chemo-radiation before prostate removal may prevent cancer recurrence
Researchers in the Oregon Health & Science University Knight Cancer Institute and the Portland Veterans Affairs Medical Center have found a combination of radiation therapy and chemotherapy given before prostate removal is safe and may have the potential to reduce cancer recurrence and improve patient survival.
PMH finding may help some tonsil cancer patients avoid chemotherapy
Clinical researchers at Princess Margaret Hospital (PMH) have confirmed that patients with oropharyngeal squamous cell cancer ("tonsil cancer") harbour a common type of human papilloma virus (HPV16), but also that such cancers are very sensitive to radiation.
Study of concurrent radiotherapy, chemotherapy shows promise in small cell lung cancer
Treating limited stage small cell lung cancer(LSCL) with a combination of accelerated high-dose radiotherapy and chemotherapy has shown encouraging results.
More Chemotherapy Current Events and Chemotherapy News Articles
 |
The Chemotherapy Survival Guide: Everything You Need to Know to Get Through Treatment by Judith McKay (Author), Tamera Schacher (Author) The first and second editions of this best-selling guide have already helped thousands of people understand chemotherapy and prepare themselves or their loved ones for treatment. The book is used as the primary chemotherapy patient education tool in outpatient clinics nationwide. This new third edition of The Chemotherapy Survival Guide includes updated information on topics including biotherapy, immunotherapy, nutrition, stress reduction, chemotherapy drugs, and more. Written by experienced oncology nurses Judith McKay and Tamera Schacher, this reassuring, optimistic guide helps readers understand their treatment options and explains in plain English how different types of chemotherapy really work. The book includes detailed advice on how to cope with and alleviate the side... |
 |
Chemotherapy and Radiation For Dummies by Alan P. Lyss (Author), Humberto Fagundes (Author), Patricia Corrigan (Author) An informative, compassionate guide for cancer patients and their loved ones Each year, more than 1 million people get treated for cancer, and most of these will undergo chemotherapy, radiation therapy, or both. This reassuring, optimistic guide helps people get a handle on treatment options and explains in plain English how chemotherapy and radiation therapy really work. It offers detailed advice on how to alleviate and cope with side effects-which range from hair loss to nausea to anemia-and describes how good nutrition, meditation, support groups, and other techniques and resources can help in the recovery process. |
 |
Physicians' Cancer Chemotherapy Drug Manual: 2009 by Edward Chu (Author), Vincent DeVita Jr. (Author) Completely revised and updated for 2009, the Physicians Cancer Chemotherapy Drug Manual is an up-to-date guide to the latest information on standard therapy and recent advances in the field. Written by world-class experts in the clinical cancer therapeutics, this essential reference provides a complete, easy-to-use catalogue of over 100 drugs and commonly used drug regimens both on-and off-label for the treatment of all the major cancers. Special features: Features new drugs: Bendamustine, Ixabepilone, and Nilotinib; Revised to reflect rapid advances in the field, incorporating new drug and treatment strategies; diagrams of drug structures and pathways for each agent; Offers a comprehensive discussion of clinical pharmacology, special considerations, indications, and dosages; Covers... |
 |
Handbook of Cancer Chemotherapy by Roland T. Skeel (Editor) The Seventh Edition of this pocket reference is a practical, disease-focused guide to the best current medical practice in cancer chemotherapy. In easy-to-follow outline format, the book provides complete coverage of the principles of rational chemotherapy, the chemotherapeutic and biotherapeutic agents available, the treatment of specific cancers, and selected aspects of supportive care. Emphasis is on the indications, dosage/schedule, potential toxicities, and safe administration of the drugs and their use in treating specific malignancies. This edition describes seventeen new chemotherapeutic agents, with particular attention to molecular targeted agents. Updated chapters on individual cancers and supportive care provide state-of-the-art treatment recommendations. |
 |
Ensure High Calcium Complete Balanced Nutrition, Ready to Use, Creamy Milk Chocolate Shake, 24- 8 Fluid Ounce Bottles by Ensure Ensure High Protein shakes are packed with 12 grams of high - quailty protein to help build muscles. And when you drink high protein shakes, you‘re getting a delicious source of protein that’s low in cholesterol and saturated fat. |
 |
Questioning Chemotherapy by Ralph W. Moss (Author) A revealing critique of chemotherapy, this book looks objectively at chemo's successes and failures. |
 |
Healthy Eating During Chemotherapy by Jose van Mil (Author) People undergoing chemotherapy often experience changes in appetite and taste. Similar problems frequently arise during radiotherapy, Another common side effect is a sore mouth, making it painful to eat. At the same time, it is vital for their recovery that patients keep their body weight up. This unique cookbook is the first of its kind, offering nutritional advice and delicious recipes to help cancer patients keep on enjoying food while fighting to get better. Devised by a chef and based on medical research, the first section of the book discusses which foods are good to eat and which are not. The second part of the book contains over 160 recipes that have been created to soothe the palate. With chapter titles like Smooth, Crispy, and Soft with a Bite, the recipes focus on the... |
 |
Pocket Guide to Chemotherapy Protocols, Fifth Edition by Edward Chu (Author) An indispensable quick reference for physicians, nurses, and other healthcare providers treating cancer patients! The updated Fifth Edition of the best-selling Pocket Guide to Chemotherapy Protocols is spiral bound and arranged alphabetically by cancer type for easy access, and contains combination as well as selected single-agent regimens for solid tumors and hematologic malignancies. In each case, the regimens selected are based on the published literature and are used in clinical practice in the medical oncology community. Pocket Guide to Chemotherapy Protocols, Fifth Edition, continues the success of previous editions by offering cancer care professionals complete, authoritative information in a convenient format. |
 |
The Chemotherapy & Radiation Therapy Survival Guide (Chemotherapy and Radiation Therapy Survivor's Guide) by Judith McKay (Author), Nancee Hirano (Author) |
 |
Coping with Chemotherapy: Compassionate Advice and Authoritative Information from a Chemotherapy Survivor by Nancy Bruning (Author) After undergoing chemotherapy herself, author Nancy Bruning decided to write a candid and authoritative book to fill the void of information available for patients facing this procedure. In this completely revised, updated, and thoroughly researched edition, she details every step of the process, providing information even doctors neglect to tell their patients, including possible sexual and emotional side effects and ways to combat them. Coping with Chemotherapy is a must-read for anyone battling cancer. |
| © 2009 BrightSurf.com |