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| http://www.latimes.com/features/health/la-he-lab18feb18,1,162154.story?ctrack=2&cset=true
N THE LAB Cancer and the bacterial connection Germs may actually help our bodies fight tumors -- which means an infection-free lifestyle comes at a price By Brendan Borrell, Special to The Times February 18, 2008 IN the 1890s, a New York surgeon named William Coley tested a radical cancer treatment. He took a hypodermic needle teeming with bacteria and plunged it into the flesh of patients. After suffering through weeks of chills and fevers, many showed significant regression of their tumors, but even Coley himself could not explain the phenomenon. Related Stories - Treatment pioneer - Red meat may boost cancer risk - Profiling the suspect His experiments were sparked by the observation that certain cancer patients improved after contracting infections. One patient experienced regression in a tumor in her arm after developing Saint Anthony's fire, a streptococcus skin infection. Doctors at the time considered Coley's bacterial mixtures to be more black magic than medicine, and with the advent of radiation therapy, the well-meaning doctor was soon consigned to the annals of quackery. But today, some scientists think Coley had it right: Germs can teach our bodies how to fight back against tumors. Dr. John Timmerman, a cancer immunotherapy expert at UCLA's Jonsson Cancer Center, says this revolution has produced "the most exciting sets of compounds in cancer immunology." These scientists have not yet proved their case. But new studies are revealing that certain cancers may be reduced by exposure to disease-causing bacteria and viruses, and pharmaceutical companies are testing anticancer treatments that capitalize on the concept by using bacterial elements to boost the body's natural immunity. The studies also imply that our cleaner, infection-free lifestyles may be contributing to the rise in certain cancers over the last 50 years, scientists say, because they make the immune system weaker or less mature. Germs cause disease but may also fortify the body, a notion summed up in a 2006 report by a team of Canadian researchers as "whatever does not kill me makes me stronger." Almost a century after Coley, in the 1980s, dermatologists began noticing that patients with severe acne, which is caused by another type of bacterium, have reduced rates of skin cancer, lymphoma and leukemia. According to a paper by Dr. Mohammad Namazi at the Shiraz University of Medical Sciences in Iran, studies showed that these bacteria, when injected into animals, appear to stimulate the immune system and shrink tumors. More recent evidence for this phenomenon comes from studies on cotton and livestock workers, who are constantly breathing endotoxins, a component of bacterial cell walls that causes swelling of lung tissue. In reports published in the last two years, Harvey Checkoway, a University of Washington epidemiologist, has found that female cotton workers in Shanghai have a 40% to 60% lower risk of lung, breast, and pancreas cancer than other factory workers. Other recent studies by Giuseppe Mastrangelo at the University of Padua in Italy found that dairy farmers exposed to high levels of manure dust are up to five times less likely to develop lung cancer than their colleagues who work in open fields. For the dairy farmers and cotton workers, "it's good news and bad news," Checkoway says. They have lower rates of cancer but tend to have higher rates of other respiratory problems. Sniffing cotton dust or inducing pimples is never going to be a therapy, he says, but studying the body's reactions to bacteria could explain why cancer rates go down upon endotoxin exposure. And that might help in developing anticancer drugs. Dr. Arthur Krieg, chief scientific officer of the Boston-based Coley Pharmaceutical Group, thinks the success of Coley's toxins comes largely from a difference between DNA of humans and bacteria and viruses. In 1995, Krieg was at the University of Iowa working with strands of DNA created in the lab, hoping to find a way to turn off genes involved in the autoimmune disease lupus. To his surprise, this DNA stimulated the immune cells he was studying in lab dishes. "I got interested, and I got puzzled," he says. His synthetic DNA contained several regions called CpGs. In humans, that region has a kind of chemical "cap" on it, but bacteria -- and Krieg's synthetic DNA -- lack that cap. Thus, in effect, exposure to that CpG makes the body "think" it's being assaulted by pathogens, and triggers the immune system to shift into attack mode -- and, in doing so, more effectively battle cancer cells. Krieg saw medical potential: Maybe one could design small drugs with CpGs in them and use them as immunity boosters. After patenting the method, he left his university job and founded Coley Pharmaceutical Group, which was acquired by the New York-based drug company Pfizer in January. Five years after his discovery, Krieg's first compound has proved safe in early trials but has not yet been proved effective. Last year, the injected compound failed to increase survival time in a trial of 1,600 lung cancer patients also undergoing chemotherapy. But Krieg thinks it will prove effective in other patients: "It's just a matter of finding the right way to use it," he says. Timmerman is a strong believer in CpGs, and has been using them with the antibody drug Rituximab in his lab research on mice. Finding the right drug combination is key, he says: "It's very naive to think that a single off-the-shelf immune stimulant is going to magically treat cancer." Krieg's CpG-based chemicals have proved useful in another arena. Because CpGs boost the immune system, they also can enhance certain vaccines. In a trial sponsored by the U.S. Defense Advanced Research Projects Agency, one of Krieg's chemicals, VaxImmune, accelerated the body's response to anthrax vaccine by a factor of two -- from 40 days to 20. Other collaborations are exploring using CpG-containing DNA to develop hepatitis B vaccines and anti-asthmatic drugs. (The company has many CpG compounds, four in clinical trials.) But Don MacAdam, chief executive of MBVax Bioscience in Ancaster, Canada, is not sure that the healing properties of Coley's fluids are due to a short strand of DNA. "The immune system is very complicated," he says, "Any of these therapies that are doing one little thing are very likely to fail." And so MacAdam wants to revive the formulation that Coley himself found most effective -- a mixture of two kinds of bacteria, Streptococcus and Serratia. Such an extract would contain naturally occurring CpGs, endotoxins and other bacterial components that may have therapeutic potential. MacAdam has solved Coley's major difficulty: maintaining consistency of the brew from batch to batch. His preparation has been tested on terminal cancer patients outside the U.S. and Canada, and he contends that 24 in 38 patients have shown signs of tumor regression, although nothing is published yet. Dr. Vikas Sukhatme, a professor at Harvard Medical School, says he hopes to run clinical trials once the product has been manufactured according to Food and Drug Administration guidelines. Other groups have been experimenting with injections of other types of heat-killed bacteria, including Myobacterium vaccae, a tuberculosis relative. In two studies in January's European Journal of Cancer, researchers report that these bacteria may help fight certain lung and renal cancers. The first study is a reanalysis of a trial with 162 patients who received heat-killed bacteria (and chemotherapy). In the original study, the treatment didn't seem to improve survival and in 2004, the company developing the therapy, London-based Silence Therapeutics, gave up on Mycobacterium. But John Stanford, a shareholder in the company and a researcher at University College London, says these studies were poorly designed and analyzed. When he and collaborators re-analyzed the results, they found that Mycobacterium injections could increase survival of adenocarcinoma patients by four months. Stanford believes that part of the bacterial cell wall switches the body from producing ineffective antibodies to sending out cancer-killing blood cells. In the second study, researchers reported that 60 renal cancer patients injected with Myobacterium survived just as long as those treated with standard chemotherapy. Stanford has formed a company, Immodulon Therapeutics, and wants to run trials with a stricter and more intense injection regime, to repeat the results and, hopefully, extend patients' lives longer. Although both Krieg and Timmerman are inspired by Coley's work, they question the philosophy behind reviving Coley's preparation and using other bacterial extracts. But, Krieg says, "as a physician you have to maintain a sense of humility and avoid being overly skeptical." Acinic cell carcinoma of the submandibular salivary gland presenting as a large cyst. Int J Oral Maxillofac Surg. 2007 Dec;36(12):1215-7 Authors: Chidzonga MM, Makunike-Mutasa R Acinic cell carcinomas are rare tumours of salivary gland origin, most commonly seen in middle-aged women and predominantly in the parotid gland. The case of a long-standing, predominantly cystic, acinic cell carcinoma located in the submandibular gland of a child is presented here. The tumour was successfully removed and there has been no recurrence. PMID: 17629459 [PubMed - indexed for MEDLINE] The Huntsman Cancer Institute - The Use of Microarray Analysis in Characterizing Mesenchymal Tissue Tumors: Differentiation of Normal, Benign, and Malignant Conditions Posted: February 1st, 2008, 10:00am EST Conditions: Soft Tissue Sarcoma; Osteosarcoma Intervention: Sponsors: State University of New York - Upstate Medical University; Huntsman Cancer Institute Recruiting - verified February 2008 Inheritance of Osteosarcoma & Paget's Disease Through Chromosome 18: Examination of Osteosarcoma Tissue Samples From Two Family Members for Loss of Heterozygosity in the Chromosome 18 Region, Genetically Linked With Paget's Disease of Bone Posted: February 1st, 2008, 10:00am EST Conditions: Osteosarcoma; Paget's Disease Intervention: Sponsor: State University of New York - Upstate Medical University Enrolling by invitation - verified April 2002 Chemo Break Benefits Some Men With Prostate Cancer Fri Feb 29, 11:47 PM ET FRIDAY, Feb. 29 (HealthDay News) -- Some men with advanced prostate cancer can safely take a break from chemotherapy, says a study by researchers at the Oregon Health & Science University Cancer Institute. ADVERTISEMENT The study included 250 men with metastatic, androgen-independent prostate cancer -- disease that spreads from the prostate and isn't affected by the male hormone androgen. The men were being treated with the intravenous chemotherapy drug docetaxel, the gold standard for this type of cancer. However, the drug can cause side effects such as hair loss, nausea, loss of appetite and increased risk of infection. An interruption in the chemotherapy regimen offers patients a much-needed break from such side effects, but it wasn't known if temporarily halting chemotherapy would lead to treatment resistance, according to background information in the study. Of the 250 men in the study, 18 percent of them received intermittent chemotherapy. The median durations of the first break from chemotherapy was 18 weeks. When they resumed chemotherapy, most of the men responded to treatment. Specifically, 45.5 percent of them responded with a greater than 50 percent reduction in prostate specific antigen (PSA) from their post-holiday baseline. Of those, just under half had stable PSA levels for at least 12 weeks, and 9.1 percent developed disease progression. Levels of PSA, a protein produced by cells of the prostate gland, are often elevated when prostate cancer is present. "We wanted to see if we could improve the quality of life for these patients by giving them time away from chemotherapy and possibly extend the time their cancer is controlled. Essentially, what we proved is that in selected subjects, chemotherapy holidays are feasible and provided meaningful breaks from treatment," principal investigator Dr. Tomasz Beer, director of the OHSU Cancer Institute Prostate Cancer Program, said in a prepared statement. The study was published in a recent issue of Cancer. Next, Beer and his colleagues want to study the use of immunotherapy to treat prostate cancer while patients are on a chemotherapy holiday. "Because we know holidays are a good thing, we want to find ways to make them even longer," Beer said. More information The American Cancer Society has more about prostate cancer Vitamin E Supplements May Raise Lung Cancer Risk By Ed Edelson HealthDay Reporter Fri Feb 29, 11:47 PM ET FRIDAY, Feb. 28 (HealthDay News) -- Vitamin supplements won't protect people against lung cancer and taking vitamin E may even heighten the risk, a new study finds. ADVERTISEMENT The survey covered the supplement-taking habits and lung cancer incidence of almost 78,000 adults in the state of Washington over a four-year period. "Our study of supplemental multivitamins, vitamin C, vitamin E and folate did not show any evidence for a decreased risk of lung cancer," study author Dr. Christopher G. Slatore, a fellow in the division of pulmonary and critical care medicine at the University of Washington, said in a statement. "Indeed, increasing intake of supplemental vitamin E was associated with a slightly increased risk of lung cancer." As reported in the March issue of the American Journal of Respiratory and Critical Care Medicine, the research focused on men and women aged 50 to 76 taking part in the four-year VITAmins and Lifestyle (VITAL) study. Lung cancer was diagnosed in 521 participants surveyed. In addition to the expected association with smoking, family history and other lung cancer risk factors, there was a slight but statistically significant association with vitamin E supplementation and incidence of the disease, the researchers found. Every increase in vitamin E of 100 milligrams per day was associated with a 7 percent rise in lung cancer risk -- translating into a 28 percent increase in risk over 10 years for someone taking 400 milligrams of vitamin E daily. "This provides additional evidence that taking vitamin supplements does not help prevent lung cancer," said Eric Jacobs, strategic director of pharmacoepidemiology at the American Cancer Society. The society does not currently recommend use of any vitamin supplement to prevent malignancy, Jacobs said. However, "our dietary guidelines do recommend eating five or more servings of a variety of vegetables each day," he noted. A representative of the supplements industry called the study results "not all that surprising." "Vitamins are essential nutrients that act to maintain health and prevent vitamin deficiency," Pamela Mason, spokeswoman for the London-based Health Supplements Information Service, said in a statement. "They were never intended to be used to prevent chronic disease such as cancer. Indeed, it would be asking a lot of a vitamin pill to expect it to prevent cancer." Since the primary cause of lung cancer is smoking, the best preventive measure is simply not to smoke, Jacobs said. Nutrients can play an auxiliary role, he noted. Anyone who cannot quit should avoid taking beta-carotene supplements, because studies have linked them to an increased risk of lung cancer, Jacobs said. On the other hand, "for former smokers, there is some evidence that vegetables high in carotinoids, such as carrots and sweet peas, decrease the risk," he said. Some vitamins have been linked to a reduced risk of other cancers, added Edward Gorham, an associate professor of family and preventive medicine at the University of California at San Diego. "We have worked with vitamin D, and we found a protective effect of vitamin D on colon cancer, breast cancer and ovarian cancer, and recently a modest effect on lung cancer," Gorham said. But that effect came not from supplements but from sunlight, which causes vitamin D to be formed in the human body, he said. "These results with multivitamins dont surprise me because there is so little vitamin D in multi-supplements, 100 or 200 International Units," Gorham said. "To achieve the effect, it takes 2,000 IU. If youre in the tropics, that amounts to 10 or 15 minutes in the sun. In southern California, it takes 10 or 15 minutes in the summer and longer in the winter because the sun angle is so low." One study has also associated vitamin D supplements with a decreased risk of colon and breast cancer in women, Gorham said. More information There's more on nutrition and cancer prevention at the American Cancer Society. |
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