Chemotalk Newsletter

Chemotalk Newsletter, Vol. 20:  December 1, 2009

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It CAN'T be the end of the year. My hyacinths are blooming, f'heaven's sake! Ah, well... And so it goes.

EARLY RELAPSE OF MS MAY MEAN FEWER ISSUES LATER

New research suggests that people with MULTIPLE SCLEROSIS who have relapses within five years of developing the disease are more likely to suffer from severe limitations in the short term than others with the condition. The findings, published in "Neurology", show that people with the disease who relapse within five years of developing it are nearly 50% more likely to need a cane to walk during that time period.

But on the brighter side, the study found that early relapses seem to be less important to the progression of the disease later in life.

"Our findings may represent an important message to people diagnosed with MS today," study author Helen Tremlett, from the University of British Columbia, Vancouver, said in a news release from the American Academy of Neurology. "Those who have a history of relapses could potentially be offered reassurance that, as time goes on, these relapses will have a diminishing effect on their everyday lives."

For their study, the researchers looked at the experiences during an average of 20 years of nearly 2,500 people with multiple sclerosis who experienced relapses in British Columbia. During those two decades, 11,722 relapses were recorded.

Tremlett said the study also supports the development of "new medications that target axonal [nerve] degeneration, which is suspected of causing permanent disability, especially for people who have had MS for many years or who are older at diagnosis." The study also reported that relapses in people younger than 25 affected disability longer than they did in people older than 35.

"There may be a longer window of opportunity for treating younger people with MS right away, changing the course of progression later on," Tremlett said.

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And more, this time about adolescence and MS...

TEENAGE OBSEITY MAY RAISE RISK OF MS

Study Shows Link Between BMI (Body Mass Index), Body Shape at Age 18 and Multiple Sclerosis in Adulthood

Obesity in adolescent girls may increase risk for MULTIPLE SCLEROSIS later in life, a study shows.

Researchers examined data on more than 238,000 women who participated in the Nurses' Health Study, which began in 1976, and the Nurses' Health Study II, which began in 1989. Participants self-reported what their height and weight were at the start of the study and what they had been at age 18. They also chose silhouettes to describe their body shapes when they were ages 5, 10, and 20 years old. Participants were between 25 and 55 years old when the studies began.

The study tracked participants for more than 40 years from both groups combined. During that time there were 593 cases of MS.

The women's body mass index (BMI) at age 18 and the way they described their overall body shape at age 20 were linked to the likelihood of developing MS in adulthood. Women who had a BMI of 30 or larger (considered obese) at age 18 had more than twice the risk of women with a BMI between 18.5 and 20.9. Normal weight BMI is 18.5 to 24.9.

The results were the same after accounting for factors such as smoking status, age, and ethnicity. There also was a link between the women who chose a larger silhouette to describe themselves at age 20 and an increased risk for MS. Being obese as determined by the BMI at the start of each study was not linked to likelihood of MS. Body silhouette self-selected at age 5 also wasn't linked to risk for developing MS later in adulthood.

"Our results suggest that weight during adolescence, rather than childhood or adulthood, is critical in determining the risk of MS," study researcher Kassandra Munger, ScD, of Harvard School of Public Health, says in a news release. "Teaching and practicing obesity prevention from the start, but especially during teenage years, may be an important step in reducing the risk of MS later in life for women."

* * *

ISTODAX APPROVED FOR CUTANEOUS T-CELL LYMPHOMA

The Gloucester Pharmaceuticals drug Istodax (romidepsin) has been approved by the U.S. Food and Drug Administration to treat cutaneous T-cell LYMPHOMA (CTCL) in people who have tried at least one prior systemic therapy.

CTCL is a form of non-Hodgkin's lymphoma, a cancer of the lymphatic system. The cancerous cells of the skin can cause itchy, disfiguring patches, and the cancer may involve other organs including the lymph nodes, blood and viscera.

Blood parameters should be carefully monitored while people take Istodax, and since it can harm a fetus, the drug shouldn't be taken by pregnant women, Gloucester said. The company warned that Istodax also may interfere will some contraceptives that contain estrogen.

Approval of Istodax followed two clinical studies of 167 patients. The drug is expected to be available in January.

* * *

BLOOD TEST MAY SPOT PANCREATIC CANCER EARLY

Texas scientists say they have found small molecules in the blood that can spot PANCREATIC CANCER, a finding that could have diagnostic implications in the future.

Levels of these molecules, called microRNAs, are elevated in patients suffering from pancreatic cancer, the fourth-leading cancer killer in the United States. The disease usually isn't diagnosed until it is in an advanced stage, when treatment is all but ineffective, the researchers say. Less than 5% of these patients survive five years past diagnosis.

"We have detected elevated levels of these microRNAs in the blood of pancreatic cancer patients," said lead researcher Subrata Sen, of the University of Texas M.D. Anderson Cancer Center's department of molecular pathology. "This is an extremely promising finding in terms of developing a blood-based assay for detecting pancreatic cancer," he said.

If such a test could be developed, the question remains: Who should be screened? Sen thinks people with a family history of pancreatic cancer and those with risk factors for the disease, such as smoking, are the first candidates for testing. However, how early high levels of these biomarkers appear in the development of pancreatic cancer is still unknown, Sen said. "That's the million-dollar question. That is something that has to be investigated with a bigger patient population."

MicroRNAs are short strands of RNA that regulate what proteins genes make, and they play an important role in both normal cells and cancerous cells. Changes in microRNAs have been seen in different cancers. Because microRNAs can be detected in blood, that may be useful in diagnosing cancer, Sen said.

The report was published in the "Cancer Prevention Research" publication.

For the study, Sen's team looked at four microRNAs that have been linked to pancreatic cancer: miR-21, miR-210, miR-155 and miR-196a. The researchers looked at levels of these microRNAs in 28 patients with pancreatic cancer and compared them with 19 healthy individuals. The team found the four biomarkers accurately detect pancreatic cancer 64% of the time. In addition, these biomarkers were able to find patients who did not have pancreatic cancer 89% of the time.

Toumy Guettouche, manager of the Oncogenomics Core Facility at the Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine, thinks this test shows promise, but is far from being ready for "prime time."

"This is an interesting diagnostic method with a lot of potential," Guettouche said. However, the sensitivity and specificity of the test is too low, he said. "This would have no chance of getting diagnostic clearance [from the FDA]," he added. It looks for 98% accuracy, he noted. In addition, Guettouche said these same microRNAs have been linked with other cancers. "The problem is to determine pancreatic cancer to begin with. What tells you that these upregulated microRNAs are from pancreatic cancer? They could be from another cancer," he said.

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IMPACT OF RA PAIN ON INTIMATE RELATIONS

A new survey of U.S. women living with RHEUMATOID ARTHRITIS reveals that RA has a clear emotional impact on people living with the disease, with loss of self-confidence seen in their sex lives, in the workplace, and in their social lives. Survey findings suggest that almost 60 percent of women living with RA in the U.S. feel less self confident in their sex-life and over a third consistently find intimate relations painful, or have even stopped altogether.

The survey, sponsored by pharmaceutical company UCB, highlights that RA was a contributing factor to a quarter of divorces among women with the disease, and that 53 percent of the single women who responded to the survey have reported their RA is an additional obstacle in finding a life partner.

"My patients feel that their discomfort is not well-understood by family members and close associates which affects their social relationships significantly," said Roy Fleischmann, M.D., Clinical Professor of Medicine at The University of Texas Southwestern Medical Center in Dallas. "Many prefer to hide their degree of discomfort from others because they feel it is too difficult to try to explain pain and decreased ability and function to those who do not have these limitations."

Pain is a huge issue for women living with RA, with 85 percent of respondents experiencing pain on a daily basis, and 82 percent taking medication every day. 68 percent of respondents claim that they constantly look for new pain relief therapies to help them cope.

Bert Kelly, Communications and Public Relations Manager, and spokesperson for UCB, commented "Many people underestimate the amount of pain associated with having rheumatoid arthritis because women tend to hide their discomfort well. Furthermore, nearly half of patients don't talk about pain control with their physician, which is a huge problem especially when a 'good day' is described as a pain free one for the majority of respondents." He continued "Over 1.3 million Americans live with the pain of rheumatoid arthritis, and so there is still a need for rapid acting treatments allowing patients more pain free 'good days' and to have an improved quality of life over a sustained period of time."

Having to choose comfortable clothes rather than fashionable ones, constant daily pain during everyday activities like cooking, emotional distress and a feeling of isolation are some of the other ways that RA impacts the lives of people living with the disease.

The U.S. 'Good Days' Survey was conducted in summer, 2009 as part of a global initiative assessing the lifestyles of women with rheumatoid arthritis in seven major industrialized countries. Objectives of the Survey included identification of the physical and emotional impact of RA on day-to-day lives of women living with the disease.

Around 300 American women aged between 25-65 years with RA for over six Months were interviewed online about the impact of the disease on their lives.

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The following piece, which appeared in the November 10 edition of The New York Times, doesn't mention transplant patients, but steroids are relevant to anti-rejection issues, as well as to the conditions considered by the author:

STEROIDS' MIRICLE COMES WITH A CAVEAT

By Jane E. Brody

Steroids - corticosteroids, that is, synthetic versions of the natural hormone produced by the adrenal glands - are indeed miracle drugs, capable of restoring the health and saving the lives of countless people with a wide spectrum of serious ailments. Prednisone may be the best known, but there are scores of others, some tailor-made to counter specific ailments.

By suppressing the immune response and inflammation, steroids can keep a host of autoimmune diseases and allergic reactions from ravaging the body. They are the cornerstone of treatments for ailments like RHEUMATOID ARTHRITIS, asthma, ulcerative colitis, psoriasis and even bad cases of poison ivy.

But as with any powerful remedy, corticosteroids come with a downside: side effects that can sometimes be as serious as the ailments they are intended to treat.

Last week I told about a friend with severe asthma who developed a rare complication that forced him to stop using the steroids that for decades had helped him breathe. He was losing his vision to steroid-caused macular degeneration. He found an alternative nondrug therapy, the Buteyko breathing method, that seems to have kept him well and steroid-free for many months.

But most people who depend on steroids are not so fortunate. For them, using the drugs year in and year out is a balancing act between benefit and risk. Knowing what those risks are and how they can be minimized can help people who depend on steroids to be alert to early warning signs of trouble and to take measures to counteract it -- in many cases before any unwanted effects occur.

COMMON SIDE EFFECTS ...

The likelihood of serious side effects depends on how long steroids are used, how they are taken, what type of corticosteroid is prescribed and how high the dose must be to keep the ailment under control. They tend to cause fewer complications when applied to the skin, or when inhaled for days or weeks for an allergic reaction or asthma. Injected steroids or oral doses taken for months or years - to treat rheumatoid arthritis, for example - are far more likely to cause serious side effects, as are injected steroids.

So an over-the-counter steroid like hydrocortisone, applied to small areas of skin to relieve a mild case of dermatitis like poison ivy or eczema, is unlikely to have any untoward effects.

But when injected repeatedly into a muscle or joint, corticosteroids can cause weakening and degenerative changes that limit their usefulness in treating chronic athletic or overuse injuries (to say nothing of their seemingly indiscriminate use by many professional athletes in recent years).

And if steroids are given intravenously, side effects may include insomnia, a metallic taste in the mouth, mood swings, nausea, rapid heartbeat and stomach irritation.

In most people, chronic use of inhaled steroids, considered medically essential to control most cases of asthma, has few if any adverse effects. Children may experience retarded growth, but studies have shown that they eventually catch up and achieve a normal height. The most common side effect, a fungal infection in the mouth called thrush, can be averted by using a spacer with the inhaler and rinsing the mouth with water afterward.

When corticosteroids are taken orally for less than three months, they are associated with temporary side effects like depression, an increased appetite, insomnia, mood swings and weight gain (partly fro water retention).

Steroids taken orally for more than three months can have more profound and sometimes irreversible effects. Serious side effects are more likely when steroids are taken in high doses for a year or longer.

In addition to weight gain, side effects may include high blood pressure, deteriorating bones that can result in osteoporosis, diabetes, thinning of the skin, muscle weakness, moon face (caused by increased fat deposits, which may also occur in the stomach, chest and upper back), cataracts, glaucoma, ulcers, easy bruising, increased sweating, acne, arterial deposits that can lead to heart disease and, because of their effect on immunity, delayed healing of wounds and an increased risk of infection that can persist for a year or more after the medication is stopped.

Excess weight resulting from steroid use is normally lost within six months to a year after the drug is topped and appetite returns to normal.

... AND HOW TO MINIMIZE THEM

When prescribed a corticosteroid, the most important thing is to follow dosing instructions to the letter. Use no more than is needed, and never abruptly stop steroids. The drugs suppress the function of your adrenal glands, which need time to recover. When the condition under treatment abates, gradually reduce the steroid dosage as instructed by your doctor.

In fact, for as long as a year afterward, you may need a "stress dose" of steroids to boost your immune response during extreme physical stress, as can result from surgery, an accident or a new serious illness.

Keep all immunizations up to date. Make sure to get a flu shot every year and, if on prolonged steroids, consider getting the pneumonia vaccine as well. Contact your doctor without delay at the first sign of what may be a serious infection, like high fever, productive cough, pain when urinating or large boils on the skin.

To minimize damage to the digestive tract, take the medication after meals or with an antacid. Let your doctor know if you develop persistent heartburn or black, tarry stools. To counter steroid-induced insomnia, take the drug early in the day.

An adequate intake of calcium and vitamin D through daily products and supplements and regular weight-bearing exercise are vital to reducing the risk of osteoporosis. If you smoke, quit; and limit alcohol to a drink a day, if that. Reduce the risk of falls by using night lights and eliminating obstacles and scatter rugs.

Steroid-induced fluid retention that causes blood pressure to rise abnormally can be minimized by sticking to a low-sodium diet. Avoid salty foods and salted processed foods and snacks. Have regular blood-pressure checks and, if the rise is serious, ask the doctor about taking a diuretic. Periodic checks for a rise in blood sugar are also important. Reduce your risk of heart disease with a low-fat, low-cholesterol diet rich in vegetables and whole grains and regular aerobic exercise.

If you notice any vision problems while taking steroids, see an opthamologist without delay. The condition could be temporary, or it could be sight-threatening, as happened to my asthmatic friend.

Rarely, damage to the hip joint called aseptic necrosis can result from long-term use of high doses of steroids. If you develop pain in the groin, a symptom of this condition, call your doctor.

* * *

STUDY EASES ARTHRITIS DRUG CANCER FEARS

Patients Taking TNF Inhibitors Had No Increase in Cancer Risk Over 6 Years

RHEUMATOID ARTHRITIS patients who take the biologic drugs Remicade, Humira, and Enbrel do not appear to have an increased risk for developing CANCER in the first few years of use, researchers in Sweden report. The study is one of the largest and longest population-based investigations ever into the cancer-causing potential of the drugs, known as tumor necrosis factor (TNF) inhibitors.

TNF inhibitors were introduced a decade ago, and they represent a significant advance in the treatment of patients with rheumatoid arthritis, Crohn’s disease, and other diseases of the immune system who do not respond to traditional treatments.

Concerns that the drugs may cause cancer emerged soon after they were introduced, and the research examining the question has been mixed. The new findings should reassure patients, but questions remain about the short-term and long-term safety of TNF-blocking drugs, says rheumatologist Eric Matteson, MD, of Mayo Clinic in Rochester, Minn.

The Swedish researchers found no difference in cancer risk among rheumatoid arthritis patients who did and did not take the drugs over six years of follow-up. "We have to remain vigilant about the possibility that these drugs are associated with an increased risk for cancer, and make sure we use the drugs appropriately," he says. "They should only be used in the patients who really require them."

ARE TNF BLOCKERS SAFE?

Also known as TNF blockers, TNF inhibitors target the TNF-alpha protein that is linked to inflammation and is overproduced in inflammatory diseases like rheumatoid arthritis. TNF-alpha is also a key player in helping the body fight cancer, leading investigators to speculate that blocking it may promote cancer growth.

In the newly published study, researchers from Stockholm's Karolinska University Hospital analyzed data from several Swedish health registries. The analysis compared cancer incidence among patients who took either Remicade, Humira, or Enbrel with patients who didn't. It included 6,366 patients who started the TNF-blocking drugs between 1999 and 2006 and roughly 70,000 patients who were either not treated or took other types of drugs.

The researchers found little difference in cancer incidence among patients who did and did not take the TNF inhibitors. Patients who took the TNF-blocking drugs for the full six years of the study had the same cancer risk as patients who took no drugs at all for their rheumatoid arthritis.

There was a suggestion of an increase in cancer risk in patients taking the biologic drugs in the first year of use, but not in the years that followed.

"Our research indicates the overall cancer risk is the same for rheumatoid arthritis patients on (immune-system suppressing) therapies and those not taking medications for the disease," lead researcher Johan Askling, MD, and colleagues write, adding that "given several remaining uncertainties, continued vigilance remains prudent."

TNF BLOCKERS AND SKIN CANCER

Two recent studies raised new fears that TNF-blocking drugs increase the risk for nonmelanoma skin cancers. In one, researchers reported that patients taking TNF inhibitors had a 34% increased risk for nonmelanoma skin cancers, compared with patients taking other disease-modifying antirheumatic drugs (DMARDs).

In another, the TNF-blocking drugs appeared to increase the risk for developing nonmelanoma cancers by about 70%, compared to treatment with a traditional DMARD.

Both were presented at the annual meeting of the American College of Rheumatology in mid-October, where experts warned patients on the drugs to check their bodies regularly for abnormal growths that can signal skin cancer. Given concerns about the potential risk for both infection and cancer in patients who take TNF-blocking drugs, Matteson says it is important that prescribing physicians use them only in patients who have few other options. He says "the jury is still out" on whether they are being over prescribed.

"The majority of patients with rheumatoid arthritis do just as well with non-biologic treatments," he says.

* * *

STEM CELL RESEARCH OFFERS HOPE FOR COLON CANCER VACCINE

Human stem cells may provide a means of creating a vaccine against COLON CANCER and other types of cancers, say American and Chinese scientists. "Cancer and stem cells share many molecular and biological features. By immunizing the host with stem cells, we are able to 'fool' the immune system to believe that cancer cells are present and thus to initiate a tumor-combating immune program," Dr. Zihai Li, of the University of Connecticut Stem Cell Institute, said in a news release.

The research by Li and colleagues is the first to make the connection between human stem cells and colon cancer vaccination. It has long been believed that immunizing people with embryonic materials may trigger an anti-tumor response by the immune system, but this theory has never advanced beyond animal research. The finding that human stem cells may help immunize against colon cancer is new and unexpected, the study authors pointed out.

In this study, the researchers vaccinated mice with human embryonic stem cells and found that the mice developed a consistent immune response against colon cancer cells. The vaccinated mice showed a dramatic decline in tumor growth, compared with non-vaccinated mice. While human embryonic stem cells triggered an immune response, artificially induced pluripotent stem cells did not, a finding that challenges the theory that induced pluripotent stem cells are the same as human embryonic stem cells and may replace them at the forefront of stem cell research, Li and colleagues said.

The study was published Oct. 7 in the journal Stem Cells. "Although we have only tested the protection against colon cancer, we believe that stem cells might be useful for generating an immune response against a broad spectrum of cancers, thus serving as a universal cancer vaccine," said co-author Dr. Bei Liu. * * *

LEUKEMIA DRUG MAY HELP SOME OVARIAN CANCER PATIENTS

A drug for people with CHRONIC MYELOID LEUKEMIA holds promise as a possible treatment for OVARIAN CANCER, new research suggests.

Researchers at the University of California at Los Angeles report that the drug dasatinib (Sprycel) limited the growth and invasive powers of ovarian cancer cells. It also proved to have even more cancer-fighting powers when it was combined with chemotherapy and used to fight certain kinds of ovarian cancer cells known as Src dependent, according to the report.

Ovarian cancer is expected to kill 15,500 women in the United States this year. The cancer is very difficult to treat. "It is important to remember that this work is only on cancer cell lines, but it is significant enough that it should be used to justify clinical trials to confirm that women with this type of ovarian cancer could benefit," Gottfried Konecny, an assistant professor of hematology/oncology and first author of the study, said in a UCLA news release.

An estimated one-third of women with ovarian cancer have the type known as Src dependent. "We were able to identify markers in the pre-clinical setting that would allow us to predict response to Sprycel," Konecny said. "These may help us in future clinical trials in selecting patients for studies of the drug."

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Happy, Healthy New Year to you all!!! See you next year...

And if you have any thoughts of how this newsletter could be improved, please email me directly, at jesmer_e@pacbell.net

Elaine Jesmer

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