ScienceDaily (Sep. 10, 2008) — Pain is one of the most common symptoms of cancer patients, yet many of them do not receive adequate therapy for the pain caused by their disease or treatments, according to a study in the September 1 issue of the International Journal of Radiation Oncology*Biology*Physics, the official journal of the American Society for Therapeutic Radiology and Oncology.

For cancer patients, pain can come from the cancer itself, chronic inflammatory changes or infections. Standard cancer treatments, such as surgery, chemotherapy and radiotherapy can also cause pain, but despite its common occurrence, pain is a frequent source of patient anxiety due to improper management.

Researchers at the University of Pennsylvania Department of Radiation Oncology in Philadelphia and the Radiation Oncology Branch of the National Cancer Institute in Bethesda, Md., sought to determine the main reasons that patients fail to receive optimal pain therapy.

Between November 2005 and April 2006, 106 radiation therapy patients responded to an Internet-based questionnaire that evaluated their medication use, pain control and attitudes toward pain medication, including prescription and over-the-counter pain medications. Fifty-eight percent reported pain from their cancer treatment and 46 percent of patients reported pain directly from their cancer, yet 80 percent of those patients said that they did not use medication to manage their pain.

Most patients said the main reason they did not take pain medication was because their healthcare provider did not recommend it. This reason was followed by a fear of addiction or dependence and the inability to pay. Some patients also reported using alternative therapies for pain relief, including physical therapy, massage and acupuncture.

“To eliminate barriers to optimal pain management for cancer patients, healthcare providers should talk with their patients about pain symptoms and pain medications,” Charles Simone, M.D., a resident at the National Cancer Institute Radiation Oncology Branch in Bethesda, Md. and lead author of the study, said. “At our institution we have taken these steps by transitioning to an electronic medical record system that has been designed to require an evaluation and documentation of patient pain levels and pain medication responses by healthcare providers at each patient encounter.”

Adapted from materials provided by American Society for Therapeutic Radiology and Oncology, via EurekAlert!, a service of AAAS.

ScienceDaily (July 11, 2008) — Medical science may be a significant step closer to climbing into the driver’s seat of an important class of immune cells, researchers at Washington University School of Medicine in St. Louis report in Nature Immunology.

The researchers showed that a single protein, HS1, enables key functions of natural killer (NK) cells, which kill early cancers and fight off viral infections. The protein allows the NK cells to pursue their targets, latch on to them and configure the cellular machinery it uses to kill them.

“Further study of how HS1 controls these processes may open up new possibilities for revving up the NK cells to fight infection and cancer,” says senior author John Cooper, M.D., Ph.D., professor of cell biology and physiology. “We also may be able to use this same protein to inhibit the activities of other immune cells and prevent them from contributing to autoimmune conditions such as diabetes.”

Cooper, who is a member of the Siteman Cancer Center at Washington University and Barnes-Jewish Hospital, studies how different types of cells use a primary component of their skeletal system known as an actin network. Earlier, his laboratory had probed the role of a protein called cortactin in specialized cells that break down bones. They showed that cortactin’s effects on the actin network made it possible for the cells to form a tightly sealed bond with bones.

“This bond is analogous to a plunger,” says first author Boyd Butler, Ph.D., a postdoctoral fellow in Cooper’s laboratory. “The cell sits down on the bone, seals tightly, and then starts secreting the acid and other compounds that break down the bone.”

NK cells have to form a similar plunger-like bond, known as a lytic synapse, with the targets they attack. They do not make cortactin but produce HS1, which is a very similar protein. Butler decided to see what would happen to NK cells in human blood samples if he turned down their ability to make HS1. The resulting cells were severely disabled: They couldn’t effectively pursue target cells, bind to them or prepare to kill them.

Prior research by other scientists had revealed that when NK cells are in motion or attacking a target, HS1 has chemical modifications attached to it at specific points. Giving the NK cells normal HS1 restored their lost functions, but when researchers gave the NK cells HS1 where these attachment points had been altered, the cells were selectively disabled. Changing one attachment point prevented them from pursuing target cells, while changing the other impaired their ability to bind to targets and kill them.

“Tight regulation is very important to prevent NK cells from harming the body’s own tissues,” Boyd says. “This ability to switch where the control signal goes makes HS1 a powerful regulator of NK cell activity–it allows the cells to provide just the right services at the right time.”

Cooper and Boyd plan follow-up studies that will start at the attachment points on HS1 and trace connections with and influences on other proteins.

“NK cells are very good at nipping early cancers in the bud,” says Cooper. “If we can better understand how they’re activated, this could lead us to ways to make them better killers of cancers and cells infected by viruses and other invaders.”

Funding from the National Institutes of Health, the National Institute of Allergy and Infectious Diseases and the Siteman Cancer Center supported this research.

Journal reference:

1. Butler B, Katendieck DH, Cooper JA. Differentially phosphorylated forms of HS1 mediate distinct functions in natural killer cells. Nature Immunology, Online June 29, 2008

Adapted from materials provided by Washington University in St. Louis, via EurekAlert!, a service of AAAS.

Damage to the lining of the mouth and a weakened immune system make it easier for infection to occur.

Oral mucositis breaks down the lining of the mouth, allowing germs and viruses to get into the bloodstream. When the immune system is weakened by chemotherapy, even good bacteria in the mouth can cause infections, as can disease-causing organisms picked up from the hospital or other sources. As the white blood cell count gets lower, infections may occur more often and become more serious. Patients who have low white blood cell counts for a long time are more at risk of developing serious infections. Dry mouth, common during radiation therapy to the head and neck, may also raise the risk of infections in the mouth. Preventive dental care during chemotherapy and radiation therapy can reduce the risk of mouth, tooth, and gum infections.

The following types of infections may occur:

Bacterial infections

Treatment of bacterial infections in patients who have gum disease and receive high-dose chemotherapy may include the following:

• Medicated and peroxide mouth rinses.
• Brushing and flossing.
• Wearing dentures as little as possible.

Bacterial infections in patients undergoing radiation therapy are usually treated with antibiotics.

Fungal infections

The mouth normally contains fungi that can exist on or in the body without causing any problems. An overgrowth of fungi, however, can be serious and requires treatment.

Antibiotics and steroid drugs are often used when a patient receiving chemotherapy has a low white blood cell count. These drugs change the balance of bacteria in the mouth, making it easier for a fungal overgrowth to occur. Fungal infections are common in patients treated with radiation therapy.

Drugs may be given to prevent fungal infections from occurring. Treatment of surface fungal infections in the mouth only may include mouthwashes and lozenges that contain antifungal drugs. These are used after removing dentures, brushing the teeth, and cleaning the mouth. An antibacterial rinse should be used on dentures and dental appliances and to rinse the mouth.

Deeper fungal infections, such as those in the esophagus or intestines, are treated with drugs taken by mouth or injection.

Viral infections

Patients receiving chemotherapy, especially those with weakened immune systems, are at risk of mild to serious viral infections. Finding and treating the infections early is important. Drugs may be used to prevent or treat viral infections.

Herpes virus infections may recur in radiation therapy patients who have these infections.

Bleeding

Bleeding may occur during chemotherapy when anticancer drugs affect the ability of blood to clot.

Areas of gum disease may bleed on their own or when irritated by eating, brushing, or flossing. Bleeding may be mild (small red spots on the lips, soft palate, or bottom of the mouth) or severe, especially at the gumline and from ulcers in the mouth. When blood counts drop below certain levels, blood may ooze from the gums.

With close monitoring, most patients can safely brush and floss throughout the entire time of decreased blood counts.

Continuing regular oral care will help prevent infections that may further complicate bleeding problems. The dentist or doctor can provide guidance on how to treat bleeding and safely keep the mouth clean when blood counts are low.

Treatment for bleeding during chemotherapy may include the following:

• Medications to reduce blood flow and help clots form.
• Topical products that cover and seal bleeding areas.
• Rinsing with a mixture of one part 3% hydrogen peroxide to 2 or 3 parts saltwater solution (1 teaspoon of salt in 4 cups of water) to help clean oral wounds. Rinsing must be done carefully so clots are not disturbed.