Chemotalk Newsletter, Vol. 10: March 1, 2009
You may have noticed that early last month I totally screwed up my working edition of Volume 10 of this Newsletter. Fortunately, there's more to talk about than that one story ...
KEY PIECE OF PROSTATE CANCER PUZZLE FOUND An unexpected discovery has turned up a key piece to the PROSTATE CANCER puzzle. The finding comes from a powerful new science called "metabolomics". Using these new techniques, scientists discovered that urine levels of an obscure amino acid derivative called sarcosine show whether a man has aggressive or benign prostate cancer. To the scientists' surprise, sarcosine wasn't just a harmless marker. Benign prostate cancer cells exposed to sarcosine suddenly turn nasty, becoming aggressive and invasive cancer cells. Aggressive prostate cancer cells that can't get sarcosine are tamed, becoming much less invasive. If confirmed and validated in larger studies, the findings have huge implications for prostate cancer treatment, says study leader Arul M. Chinnaiyan, MD, PhD. and professor of pathology and urology at U of Michigan, Ann Arbor. "We have tantalizing evidence that this sarcosine pathway may be involved in the pathogenesis of prostate cancer," according to Chinnaiyan. "Therapeutically, we could envision small molecules or antibodies that might inhibit some of the pathway components that lead to sarcosine upregulation." If the finding leads to new tests, it would have a huge impact on how prostate cancer is treated, because one of the biggest problems is over-treating patients because doctors can't distinguish aggressive from indolent disease. The findings validate metabolomics and a brand new technology using computer-driven robotic machines that can rapidly identify all the various chemicals that build up inside the cells of the body. This chemical buildup consists of metabolites -- the end products of the vast number of biochemical reactions that take place within cells. By comparing the metabolites from normal cells to those of indolent and aggressive prostate cancer cells, Chinnaiyan and colleagues detected at least 10 metabolites that distinguish normal cells from cancer cells -- and which increase or decrease in frequency as cancer cells get more aggressive. Once identified, a simple urine test can detect the metabolites. And if detecting sarcosine gives a lot of information, detecting additional cancer-specific metabolites will make an eventual test exponentially more useful. Right now, just looking for sarcosine in urine would not give much information. Large numbers of men, at various stages of prostate cancer, will have to be enrolled in validation studies. But these future tests may someday make needle biopsies of the prostate obsolete. * * *
MS TRIAL ALERT: CLINICAL TRIAL OF SEX HORMONE ESTRIAL RECRUITING WOMEN
The National MS Society is funding a team of investigators at 16 medical centers to conduct a two-year, controlled clinical trial of an estrogen (estriol) added to standard therapy to treat MS. Investigators administer either oral estriol along with Copaxone® (glatiramer acetate) or Copaxone plus inactive placebo to 130 women with RELAPSING-REMITTING MULTIPLE SCLEROSIS. If successful, this clinical trial could lay the groundwork for a larger, definitive trial that could lead to a new treatment option for women with MS, utilizing a pill, not an injection.
Importantly, the exclusion criteria for the study have recently changed, such that patients previously treated with an interferon or Copaxone will no longer be excluded.
TRIAL DETAILS/ELIGIBILITY: The two-year study is a double-blind, placebo-controlled trial that will take place at 16 sites in the U.S. The team is evaluating effects of the treatment combination on relapse rates and several clinical and magnetic resonance imaging measures of disability progression.
This study is being funded by the National MS Society – through the support of the Southern California Chapter and other chapters and private donors – and the National Institute of Neurological Disorders and Stroke. Adeona Pharmaceuticals is providing drug for the trial. RATIONALE: Estriol levels rise to very high levels naturally during late pregnancy, a time when most women’s MS disease activity declines. This led some to suspect that estriol may be responsible for this easing of symptoms during pregnancy. Dr. Rhonda Voskuhl (University of California, Los Angeles) and others explored this lead in mice with MS-like disease, and later, with National MS Society support, Dr. Voskuhl conducted a small, early-phase trial of estriol in 12 women with MS. Results in mice showed that estriol treatment was indeed protective. Results in the pilot trial showed that estriol treatment decreased disease activity in women with relapsing-remitting MS. According to Dr. Voskuhl, the trial principle investigator, in using estriol they “aim to simulate some of the disease protection offered by pregnancy. We are very enthusiastic about this new agent since it has decades of known safety and since it will be given as a pill, not a shot.” She further states, "Estriol treatment also has the potential to be more potent in halting disability in MS, since estrogens have been shown in animal models to be not only anti-inflammatory, but also to directly reduce brain injury."
Contact: For more information, please see the study’s listing (NCT00451204) on ClinicalTrials.gov.
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More good news for people with MS...
NEW DRUG HELPS MS PATIENTS WITH WALKING
The drug fampridine, developed by Acorda Therapeutics and currently going through the process of regulatory approval, has been successful in a clinical trial in treatment of a specific symptom of MULTIPLE SCLEROSIS: walking.
In the medical journal Lancet, the lead author of the study, Dr. Andrew D. Goodman, says "This is the first thing that has ever been able to improve the impairment to some degree."
The existing drugs for MS are thought to work through the immune system to reduce relapses and slow the development of problems. Acordia's fampridine, by contrast, improves the ability of the nerve fibers to transmit signals and could be used, along with other medicines, to improve walking in people who already have that disability.
Even though those who responded to the drug remained disabled, they reported in questionnaires that they could sense the improvement in their ability to do such things as walk outside, climb stairs or stand in one lace for a prolonged period.
There have been signs since the 1980s that fampridine could help people with MS, but it also caused dangerous seizures. Acordia's formulation, taken as a pill twice a day, releases the drug gradually into the bloodstream, preventing buildup of dangerous concentrations. In the trial, only one person suffered a seizure.
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STRESS MAY SPEED MELANOMA PROGRESSION According to an Ohio State University study, stress appears to hasten the progression of aggressive or advanced MELANOMA, but commonly prescribed blood pressure drugs may slow the disease and improve the quality of patients' lives. In laboratory tests, the researchers exposed samples of three melanoma cell lines to the stress hormone norepinephrine and looked for changes in the levels of certain proteins released by the cells: vascular endothelial growth factor (VEGF), which stimulates the growth of new blood vessels to feed a growing tumor; and interleukin-6 (IL-6) and interleukin-8 (IL-8), which play a role in tumor growth. When exposed to norepinephrine, all three melanoma cell lines increased production of the three proteins. In C8161 cells -- the most aggressive and advanced form of melanoma -- there was "a 2,000% increase in IL-6. In untreated samples from this cell line, you normally can't detect any IL-6 at all," says Eric V. Yang, a research scientist at the Institute for Behavioral Medicine Research. "What this tells us is that stress might have a worse effect on melanoma that is in a very aggressive or advanced stage, and that one marker for that might be increased levels of IL-6". The researchers found that norepinephrine molecules bind to receptors on the surface of cancer cells, which stimulates the release of the pro-cancer proteins. Further tests showed that common beta-blocker blood pressure drugs significantly reduced melanoma cells' production of IL-6 and the other two proteins, by blocking the receptors on the surface of the cancer cells. The findings, published in the February issue of the journal Brain, Behavior and Immunity, suggest that beta-blockers may help slow the progression of melanoma, Yang and colleagues said. * * *
NEW TEST FOR RA
The biotech firm Axis-Shield has developed a revolutionary new test for RHEUMATOID ARTHRITIS that detects disease before it manifests itself, ensuring sufferers receive early treatment. The test kit detects the presence of protein antibodies, a sign indicating the subject is likely to contract the chronic auto-immune disease. It is currently on sale but has yet to receive clearance in the American market. Dr Thomas Skogh of Linkoping University Hospital in Sweden said the new test had the potential to help a huge a number of patients. “The introduction of tests recognizing anti-citrullinated protein antibodies has caused a revolution in rheumatology,” he said. “The antibodies may occur in the blood long before the onset of symptoms.”
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MORE about the relevance of the IL-6 protein:
NEW CLUES TO STOPPING COLITIS-LINKED CANCER
A new study from U of California, San Diego School of Medicine indicates that two immune system proteins may someday help doctors treat and prevent colitis-associated cancer. The Interleukin 6 (IL-6) cytokine, a protein released by cells in the immune system, plays a key role in tumor production of colitis-associated cancer. This work by IL-6 appears dependent on STAT3, a transcription factor that encourages cancer development. The findings suggest that targeting IL-6 and Stat3 might be a way to stop or treat CAC, said lead researcher Michael Karin. For example, when researchers removed STAT3 from intestinal epithelial cells of mice in the test, the development of colitis-associated cancer stopped. Inflammatory bowel disease, such as ulcerative colitis, puts people at a greater risk of developing colorectal cancer, and nearly half of people with the malignancy die from it. The new study backs previous work by the San Diego researchers, who suspected that IL-6 helped foster chronic inflammation and the survival of malignant cells that helped promote cancer.
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ENROLLMENT BEGINS IN PHASE 2 TRIAL OF ORAL MUCOSITIS DRUG
SciClone Pharmaceuticals, Inc. has announced the enrollment of its first patient in its phase 2, multi-center, randomized, double-blind, placebo-controlled study to assess the safety and efficacy of SCV-07 for prevention of oral mucositis in patients receiving radio-chemotherapy for the treatment of HEAD AND NECK CANCER.
Mucositis is the painful inflammation and ulceration of the mucous membranes lining the digestive tract, usually as an adverse effect of chemotherapy and radiotherapy treatment for cancer, and can affect up to 100% of patients undergoing high-dose chemotherapy and hematopoietic stem cell transplantation, 80% of patients with malignancies of the head and neck receiving radiotherapy, and a wide range of patients receiving chemotherapy.
“Despite its frequency, pain, adverse impact on health, and healthcare cost, there are very few treatment options available for oral mucositis,” said Stephen T. Sonis, DMD, DMSc, Brigham and Women’s Hospital, Boston, MA. “Data from the preclinical studies of SCV-07 were very promising, showing a compelling prevention of oral mucositis. Intriguingly, the preclinical models also showed A DECREASE IN TUMOR GROWTH in addition to preventing oral mucositis. And, SCV-07 was well-tolerated. Based on these significant findings, we believe that further studies of SCV-07 for the prevention of oral mucositis in head and neck cancer patients are warranted.”
Currently, there is no approved intervention for oral mucositis induced by radiation or radio-chemotherapy, and there is only a single approved therapy for oral mucositis associated with the administration of conditioning regimens prior to stem cell transplant for the treatment of cancer.
The study will be conducted at approximately 15 to 20 centers in the United States, and will include three treatment cohorts of 20 patients each. Each cohort will receive either placebo, SCV-07 at a dose of 0.02 mg/kg, or SCV-07 at a dose of 0.10 mg/kg. The treatment period will be approximately seven weeks depending on the patient’s prescribed radiation plan, with a follow-up visit approximately 30 days following the last day of radiation therapy. The primary efficacy endpoint is delay of onset of severe Oral Mucositis.
For more information on SciClone’s phase 2 trial of SCV-07 in the prevention of oral mucositis, visit http://www.clinicaltrials.gov <http://www.clinicaltrials.gov/> .
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NOTE: Remember that glitch, when I sent a partial newsletter in the middle of last month? Well, a very observant editor at CURE MAGAZINE responded with the following:
"We just did a big story on KRAS (the gene mutation that interferes with succesful treatment for some lung and colon cancers)!!! Check it out online."
So...do as the lady suggests, get the full story from "www.curetoday.com".
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FINALLY, on a personal note, many of you know about the "scare" I had recently. I didn't see any reason to do details in my email, especially since everything turned out so well. But I keep thinking there's something more to be said about trusting your instincts about your own body.
We're given so much information based on statistics and the experience of our medical team that we have to keep reminding ourselves of the VERY important truth: that each of us is unique. That means all that information has to be filtered through our knowledge of our own bodies, or what we've observed, as friends or caretakers, about people we care about who are facing decisions about their health.
Even if I had remembered that when I was a kid I had constant problems with "reactive" glands, problems that seemed to come and go for no reason, I STILL would have opted to have that gland removed and biopsied. Weighing all the options, it was clearly the right thing to do. But what we add to our medical histories through our memories can help our doctors refine our treatments. They only know the information we provide. And every detail we can add, even if it seems irrelevant, should be passed on to our medical team. Yes, they're the experts. But because we're all unique and rarely conform exactly to statistical predictions, every piece of information we can give them fills in another pixel or two in the picture of our health histories.
Yes, we need our doctors. But they need us to be proactive.
And if you have any thoughts of how this newsletter could be improved, please email me directly, at firstname.lastname@example.org