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Meg Mangin R.N.
Research Team
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Posted: Wed Oct 4th, 2006 23:44 |
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Antibiotic Fights Chlamydia-Linked Eye Cancer
(filelink)
WEDNESDAY, Oct. 4 (HealthDay News) -- The antibiotic doxycycline is proving an effective treatment for a lymphoma of the eye linked to chlamydia infection, Italian researchers report.
This cancer of the eyelids and related tissues is called "ocular adnexal lymphoma of the MALT-type" (OAL). It isn't fatal but can affect a patient's quality of life. Previous research had suggested an association between OAL and infection with the Chlamydia bacterium.
This study, published in the Oct. 4 issue of the Journal of the National Cancer Institute, included 27 OAL patients treated with doxycycline for three weeks.
Treatment with doxycycline was successful for two-thirds of patients, reported a team from the San Raffaele H. Scientific Institute in Milan.
"Our prospective trial revealed that doxycycline is a fast, safe, and active treatment for OAL, both at initial diagnosis and at relapse," the study authors wrote.
They suggested that the antibiotic may prove useful even in OAL patients where other treatments have failed. The drug also offers patients an alternative to chemotherapy and radiation, which can cause serious side effects.
More information
The American Cancer Society has more about eye cancer.
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Aussie Barb
Research Team
| Joined: | Thu Jul 22nd, 2004 |
| Location: | Australia |
| Posts: | 19241 |
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Offline
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Posted: Thu Oct 26th, 2006 05:21 |
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(filelink)
Chemotherapy
"If you are given chemotherapy it will destroy your immune system, but the bacteria continue to multiply unchecked, and you will relapse as they withdraw the chemotherapy.
Chemo not only shuts down any healing of your immune system, it does not guarantee reduction of the cancer risk in any sigificant way. Ask Doc for the statistics on the procedures he is recommending.
..Trevor..
Radiation
"Radiation is immune suppressive?" - poppycock.
Of course radiation profoundly affects the immune system. What do you think happens to the cells that the radiation kills?
..Trevor..
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Do chemo or radiation therapy lower/alter 1,25 D levels?
This is an incredibly complex question, because it contains the assumption that all diagnoses of Cancer are indeed cancer. However, Oncologists still have a lot to define about the disease they study, and, in particular, how it relates to inflammatory disease. Consequently, tests are still used to diagnose cancer which could make a false positive - a cancer diagnosis where there is no cancer.
At the recent "Host Defenses" conference at San Diego a Senior Investigator from the NIH started his talk by saying. "Gentlemen, let's all start by agreeing on one thing - Inflammation induces Cancer." He is correct of course, all the recent studies have been pointing fingers at the chemokines, particularly the Cellular Adhesion Molecules. Some have also been even more to the point, such as this one, showing that a competent immune system Th1 response was necessary to fight melanoma.
Prior to their discovery, researchers believed that a Th1 response was important, but that it worked primarily by activating another type of T-cell called a cytotoxic T-cell (CTL). These results suggest that it may be important to monitor Th1-type immunity in addition to CTL immunity when evaluating patients' responses to immunotherapy.
So you can see that cancer is not necessarily an "all or nothing" issue. It is complex, and we are in no position to discuss the scientific issues here.
Immunosuppressive Chemo is very likely to affect 1,25-D levels. We have no data on radiation, although we did track one anecdotal case of a pulmo using whole-body radiation to try and "cure" advanced sarcoidosis. The patient died after months in agony, and after months spent in hospital. Beyond that, there just is no reliable data that I have seen.
..Trevor..
Dec07 A downside of immunosuppressive chemotherapy or irradiation could be the escape of dormant tumour cells from immune control. Dormant cells themselves are likely to be less susceptible to these treatments, which primarily target rapidly dividing cells.
It is important to clearly establish that metastatic cancer (i.e. cancer that has escaped the immune system) is present before aggressive cancer treatment is undertaken. The treatment of dormant tumours (those in equilibrium with the immune system) with immune suppression could lead to full blown cancer where it heretofore did not exist.
If there is, for example, an old 'Ductal Carcinoma In Situ', then the mass should probably be removed as it will be quite a load on the immune system to eventually 'dissolve' the old tumor. But, unless there are clear signs that there is active metastasis, I believe it is incorrect to assume that follow-up treatment (beyond the MP) is required. Once somebody has gotten 2 years (or so) into the MP, their immune systems should be functioning well enough to deal with moderate metastasis.
I assume that many folk come to the MP with some form of tumor present, as untreated Th1 patients are known to be at very high risk for cancers. But I also assume that as they progress through to recovery with the MP, their immune systems will function well enough to contain, and eventually eliminate, any metastasis (spread of the tumor).
..Trevor..
Last edited on Sat Dec 15th, 2007 17:10 by Meg Mangin R.N.
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Barb: Dx Inflammatory Disease Endocrine Imbalance 2003| 24+ years not Dx| ABCofMP
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Meg Mangin R.N.
Research Team
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Posted: Sun Oct 29th, 2006 12:53 |
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An interview with Dr. Alan Cantwell MD
(filelink)
This interview was conducted by Ron Falcone on October 24, 2006
The Cancer Bacteria Forum
EDITOR'S NOTE: Dr. Alan Cantwell has investigated the phenomenon of cancer bacteria for over thirty years. A graduate of New York Medical College, doctor Cantwell completed a residency program in dermatology at Long Beach Veteran's Administration Hospital in Long Beach, CA and then practiced in the dermatology department of Kaiser-Permanente in Hollywood, California, from 1965 until his retirement in 1994. Dr. Cantwell is the author of more than thirty published papers on breast cancer, lymphoma, Kaposi's sarcoma, Hodgkin's disease, lupus, scleroderma, AIDS, and other immunological diseases. These papers have appeared in many peer reviewed journals, including Growth, International Journal of Dermatology, Journal of Dermatologic Surgery and Oncology and Archives of Dermatology. He is also a prolific author (see Aries Rising Press for a list of his titles).
CBH: Hi Dr. Cantwell and thanks very much for joining us today at the Cancer Bacteria Homepage. It is an honor having you visit with us. To begin, can you tell us how long you have been a physician and what your specialty was before becoming interested in cancer bacteria research?
Cantwell: I received my MD degree from New York Medical College in 1959. After an internship at Mercy Hospital in San Diego, I served as a Captain in the Army Medical Corps for two years in post-war Korea, and later began a three-year dermatology residency program at the VA in Long Beach, CA, in 1962. In the fall of 1963 I read a medical report concerning tuberculosis-type infections of the skin following prescribed injections of vaccines and antibiotics. This quickly led me to investigate unusual cases of "panniculitis" (an inflammation of the fat) in several of my VA patients who had injections. I was able to show these patients were infected with peculiar and unusual "acid-fast" bacteria. This was reported in The Archives of Dermatology in 1966. My panniculitis work segued into scleroderma research where I was also able to show acid-fast, TB-like bacteria in this dreadful disease, currently considered a disease "of unknown etiology." When my first case of acid-fast bacteria in scleroderma was reported in The Archives, also in 1966, I learned about Virginia Livingston MD, who first reported similar bacteria in scleroderma back in 1947 in the Journal of the Medical Society of New Jersey.
CBH: And when did you first become interested in cancer bacteria research? Was your initial interest in cancer bacteria related to skin diseases?
Cantwell: When I first met with Virginia (Livingston) in San Diego, I learned of her many years of research into acid-fast "pleomorphic bacteria" that she and her associates had discovered and studied in every case of cancer that they investigated.
CBH: As a young physician, were you initially skeptical of the idea of a cancer bacterium? If so, what convinced you that there might be something to the theory?
Cantwell: I never believed in my wildest dreams that I would ever study the bacterial cause of cancer. It was inconceivable to me that scientists could have failed to recognize a microscopically visible infectious bacterial agent in cancer. I soon learned that Virginia and her colleagues suffered greatly for their belief and research into the bacterial cause of cancer. For her whole life, Virginia was marginalized and condemned by her colleagues for her attempts to treat cancer patients with vaccines, antibiotics, diet, and supplements.
CBH: Were you surprised at your findings from a microbiological standpoint? What I mean is, did your findings clash with the known tenets of microbiology? And if so, can you tell us briefly, how?
Cantwell: I must admit that I never studied bacteria in cancer until the mid-1970s. There were two reasons for this. First, I thought that the scleroderma work would be confirmed by other dermatolgists and scientists, and that I would be content to have discovered a cause of that disease. But after a half-century, it is sad to relate that Virginia and I are the only two physicians who have ever presented evidence for this. Secondly, I worked for an HMO and I didn't want to be regarded as a "quack" like Virginia had been labeled, so I avoided the cancer bacteria controversy as long as I could. However, in the mid-1970s I found pleomorphic bacteria in sarcoidosis, and also in a lymphoma that appeared in one of my patients with sarcoidosis. I was amazed to see how easy it was to detect these bacteria in sarcoidosis and lymphoma, and in these two diseases also "of unknown etiology." Once I realized that Virginia was so correct in her declarations of a cancer bacterium, my research progressed rapidly in studying other forms of cancer, as well as immune diseases, like lupus erythematosus. At that point I finally had attained the courage of my convictions, and was willing to take a stand along with Virginia.
CBH: Dr. Cantwell, much has been made about bacterial pleomorphism, and you have been one of that phenomena's most knowledgeable investigators. Can you tell us just how pleomorphism might have, and still does, create misunderstanding and confusion among researchers?
Cantwell: One cannot begin to understand and recognize bacteria in cancer and certain other immunologic diseases unless one has a little knowledge of bacterial pleomorphism the idea that bacteria can exist in more than one form. I have written about (and illustrated) acid-fast pleomorphic bacteria. My most important contribution to the etiology of cancer was to demonstrate how these bacteria appear microscopically in cancer tissue. Unfortunately, these bacteria in tissue are ignored or are unrecognized and/or are dismissed by scientists are non-bacteria. Fortunately, these bacteria in cancer can be viewed by interested persons on the Internet in a series of my papers posted at the http://www.joimr.org website. There, one can click on color photos of these bacteria and visualize them full-screen in size. These papers also carry an extensive bibliography of dozens of scientists and doctors worldwide who have reported similar bacteria. The fact that this great body of work has been ignored or overlooked or condemned is surely the biggest tragedy in modern medicine, at least in my view.
CBH: As a follow up, would it be fair to say that depending on how microbes are grown, fed, and when they're observed, mistakes in identifying them can still be made---even with today's biotechnologies?
Cantwell: Microbiologists are terribly concerned about precise identifications of microbes associated with cancer. But at the same time these bacteria are thought not to exist or to play any role in the etiology of cancer. My belief is that these cancer microbes have to be recognized first, and only then can scientists quibble about exactly what to name them. Also in the laboratory, one TB-like microbe we isolated from scleroderma became more and more fungus-like as it aged in the lab, and experts in fungal identification were unable to precisely classify the microbe at that stage of development. I have also observed on one occasion a scleroderma bacterium that changed species back and forth, depending on the lab media used for growth.
CBH: Do you believe that knowledge about a cancer bacterium can help in achieving a better understanding of AIDS and AIDS-related treatments?
Cantwell: Also unrecognized and unaccepted in AIDS is my research showing that cancer microbes are present in AIDS --from the very beginning of the disease, the so-called "lymphadenopathy syndrome" up to death when these bacteria have been shown in many organs at autopsy. In addition, cancer bacteria play a role in the development of Kaposi's sarcoma, the most common cancer in HIV infected men. These papers can also be found on PubMed.* It may eventually prove that this unrecognized bacterial infection in AIDS does more harm that HIV does.
CBH: Do you believe that if a room full of orthodox, traditional cancer scientists agreed to work alongside you and were genuinely open-minded to the knowledge you have acquired, they would eventually observe the same phenomena and come to the same conclusions you have?
Cantwell: It is sad for me to say that the minds of medical doctors are totally closed on the subject of the cancer microbe. For more than four decades I have been unable to convince any physician that my research is important and should be studied by others. On the other hand, I have never had any physician present any evidence that the cancer microbe work is wrong.
CBH: Dr. Cantwell, if there is indeed such a thing as a cancer-causing bacterium, then how can it be that the most clever scientists in the world have failed to see it, or continue to be ignoring it? Is that really possible or admittedly too fantastic to accept?
Cantwell: The identification of simple-to-see cancer microbes would cause havoc in the cancer treatment industry. It would also be the biggest embarrassment to befall modern medicine. It's the equivalent of trying to convince scientists that the world is flat!
CBH: Can you tell us a little about your relationship with Virginia Livingston? A little about her and what she was like?
Cantwell: Virginia was a dear friend who more than anyone on the planet influenced my life's work. I consider her my "scientific soulmate". She was a dynamic woman, as successful in her cancer work as she was in business. At the same time, I know it was always painful for her to be such an outsider and a scientific rebel, and to have her ideas and published work condemned. We would commiserate together on the impossibility of getting the cancer work accepted by other physicians. She was convinced that the evidence for the cancer microbe in the scientific literature was overwhelming. In her view, the insurmountable problem was that "doctors don't read." I have written a new book about Virginia and her three colleagues (microbiologist Eleanor Alexander-Jackson, cell cytologist Irene Corey Diller and world-famous biochemist Florence Siebert). In that book, I show how Livingston and her colleagues believe they had collectively solved the riddle of the etiology of cancer. Titled FOUR WOMEN AGAINST CANCER, it is an attempt to explain pleomorphism and to picture these microbes in cancer, as well as to descibe the fabulous cancer research performed by these four remarkable women, all people that I was able to know personally, and sadly all of whom are passed away.
CBH: Do you think she was a genius whose achievements will someday be known to every future medical scientist and practitioner, or is that too optimistic an assessment?
Cantwell: The cancer microbe has been around since the late nineteenth century when the well-respected Scottish pathologist, William Russell MD, wrote on "the parasite of cancer." But powerful forces in medical science have always been against this research, I presume for monetary and egotistical reasons. That the cancer microbe has not been accepted for more than a century is truly the "eighth wonder of the world." I am sure one day medical historians will give us some good reasons for this. But remember that germs were known for more than a century before doctors finally admitted they caused human disease. Personally, I think most of us give ourselves too much credit in thinking how smart we are, whereas in reality, we aren't.
CBH: What are your predictions for the future of cancer bacteria research? Are at least some scientists starting to "get it" or are they a long way off from really taking a look at this most perplexing controversy?
Cantwell: In my study of the cancer microbe, I had to learn and observe what the bacteria looked like in the laboratory, as well as to consider how they might appear in the cancerous tissue. Unfortunately, pathologists and microbiologists are on two different planets. Pathologists pay little attention to germs in a laboratory, and microbiologists pay little attention to what there germs do when they infect human tissue that is subsequently examined by pathologists. Both pathologists and microbiologists are loathe to admit that what Virginia and I, and dozens of other researchers have reported, are indeed bacteria. Pleomorphism is still not accepted by many microbiologists, and the study of pleomorphic "cell wall deficient bacteria" in human disease is still in its infancy. For an up-to-date 2006 review of cell wall deficient forms of acid-fast mycobacteria, go to: http://www.vri.cz/docs/vetmed/51-7-365.pdf
CBH: In your opinion---and we realize you can only give an opinion---do you think cancer mortality could theoretically be lessened if treatments based on bacterial vaccines such as Livingston and others have proposed, were used on a large scale?
Cantwell: It is an axiom in medical science that one can't adequately treat a disease unless you know what causes it. That was certainly the case with AIDS until HIV was identified and anti-viral therapies developed. Similarly, it is my opinion that the treatment of cancer will remain dismal until these bacteria are recognized as cancer-causing agents by the scientific and cancer establishments. At that time, treatments will surely be devised to eradicate or minimize these cancer-causing microbes, including further research into the use of autogenous vaccines, as recommended by Livingston and others. I sincerely believe that Virginia Livingston will one day be honored at the greatest scientist of the twentieth century. I just hope that it won't take until the next century to accomplish this.
CBH : Absent the recognition of just what these bacteria are, would you say then, a treatment approach involving individually derived bacterial vaccines---i.e. bacteria cultured from each cancer patient---might serve as a potentially useful treatment strategy right now, as Livingston had advocated?
Cantwell: Yes, autogenous vaccines that were used by Virginia as an attempt to rev up the immune system could certainly be employed. However, this would require that bacteria be cultured from the patient's cancer tumor (or perhaps the blood or the urine) and then utilized to make a vaccine. This would require a lab able to perform this, as well as someone knowledgeable in making "autogenous" vaccines. For many years Livingston used John Majnarich of Seattle to make her vaccines. According to a current Google search, Majnarich's lab still provides autogenous vaccines to Edwin McClelland MD of San Diego, who worked briefly at the now defunct Livingston Clinic.
* [NOTE: For those wishing to see a list of Dr.Cantwell's published abstracts, click this link] http://www.rense.com/Datapages/drcantwelldata.htm
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Meg Mangin R.N.
Research Team
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Posted: Tue Nov 28th, 2006 23:17 |
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(filelink)
The politics of cancer
I made a cancer-themed presentation May 21, 2007 at the DMM2007 conference at Harvard with the best cancer-minds in the world. But it is a long step from these early thoughts to any clinical application of the MP pathogenesis in any of the many varieties of cancer.
Even if I was prepared to stick my neck out and punt for the goal-posts right now, there would be few oncologists who would give that punt more than a 0% chance of success.
Cancer is a big business. The public have been very effectively persuaded that oncologists know a lot about cancer, and that cancer therapies are effective. I believe that oncologists are prepared to defend that business model, regardless of what the science might say...
The resistance of oncologists is not entirely based on business interest. Many are highly motivated professionals. And most would still be not fully up-to-date with the research knowledge about how the inflammatory cytokines and chemokines are so important to metastasis.
Many of the folks who were at the Harvard conference are still unable to put together all the pieces of the puzzle. We have been lucky, as at least the characteristic infection is pretty well known to us, and therefore it is less of a leap for us to deal with the other pathogenic issues. But those with whom I did share our knowledge could (mostly) see how important our description of the inflammatory process really is.
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Meg Mangin R.N.
Research Team
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Posted: Thu Jan 11th, 2007 20:06 |
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(filelink)
Bladder cancer
Diagnosis
I believe the specific information in a biopsy report may depend on the institution's customs and the type of procedure that was performed.
Here's some more information you might find useful. The National Cancer Institute's website says, "A biopsy for bladder cancer is usually done during cystoscopy."
When the cystoscopy is performed, the bladder wall may be irritated with a wash, and a specimen may be collected from that wash. These wash cells are then reviewed by a pathologist, who determines what type of cells are visible under a microscope. Here is an overview of the general diagnostic process.
The NCI's booklet on bladder cancer explains that bladder tumors may be either benign or malignant. This article discusses how a second opinion of a pathological diagnosis of bladder cancer may affect treatment choices. ~Belinda
Treatment with BCG
BCG is live bacterium, Mycobacterium bovis. It is fingered as having directly caused Sarcoidosis, for example:
http://tinyurl.com/34x2bs
http://tinyurl.com/2sjtx2
IMO, it is laughable that anybody would suggest its use for prophylaxis in this day and age. A small RCT was conducted on its use in Cancer fifteen years ago
http://tinyurl.com/2nsyh9
The author recently backed off from his 1992 blanket recommendations
http://tinyurl.com/2bc84b
Here is what the CDC has to say about its use in prophylaxisis against TB
http://www.cdc.gov/nchstp/tb/pubs/tbfactsheets/250120.htm
IMO, not only is the answer "hell, no" IMO you need to re-evaluate the suitability of the physician who suggested this therapy to a sarcoidosis patient, without at least warning about the risk of resulting infections and disease.
I would imagine it 'works' by changing the path of 'successive infection' which leads to immune disease (and cancers). My guess is that it is such an insult to the immune system that the body starts focusing its defence against the Mycobacterium bovis and away from the chronic pathogens fueling the inflammation/cancer...
Ask Doc for the statistics on the procedures he is recommending. Didn't you read the Pubmed references I gave? Their idea of success with BCG is possible "survival" at the 18 month and 5-year marks. In other words, no guarantees, and if you ask why, they will say "cancer is a killer" rather than the real reason "we don't know what causes cancer, or how to cure it."
..Trevor..
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There is a new paper out linking BPH (benigh prostatic hypertrophy) and bladder health with the VDR and 1,25-D. It might help Doc understand better where we are coming from. Remember that Benicar is also a VDR agonist, like the drug described here:
Human Bladder as a Novel Target for Vitamin D Receptor Ligands
This paper contains more information about BPH.
Members' experiences
July 08...Interview with Gene Johnson (Sarcoidosis, bladder cancer) Gene's MP Journey, cancer free for over a year.
See also Vitamin D and cancer.
Last edited on Mon Jul 21st, 2008 02:57 by Meg Mangin R.N.
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Meg Mangin R.N.
Research Team
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Posted: Mon Feb 5th, 2007 02:22 |
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(filelink)
Difficult decisions
....you have a lot of important decisions to make, and it is very tough when you are being torn from side to side, but you need to know the truth....
The moderators here have all spent time working in the health-care industry. We have seen it from the inside. We try and communicate our insights, within the limitations placed on our speech by not wanting to appear to be back-stabbing our colleagues, and inhibited by the possiblity that we will (again) get reported to the Medical Board by someone we are trying to help So we can't tell you the whole story, only that part which is fit to print
Healthcare is a huge industry. As Pink Floyd once wrote, "Welcome to the machine." (a brilliant set of lyrics to study, incidentally)... Physicians bury their mistakes. So do nurses, and even researchers
Physicians need absolute authority in order to do their job properly. 90% of the time they are often less than sure about the effectiveness of the therapy they are advising. However, without total respect from the patient the probability of compliance is close to zero. So the aura of authority is paramount.
So have a heart for the person in the white coat. But just don't get into the situation where you end up with a broken heart
..Trevor..
There is a need to maintain a clinical precision whenever 'Cancer' is being discussed. Otherwise it is too easy to allow emotional issues to overwhelm our ability to reason clearly.
We do know that there is a key protein called the Metastasis Suppressor Protein which is transcribed by the VDR. Benicar should activate transcription of this gene, and its function is pretty obvious from its name Obviously the Th1 diseased VDR does not transcribe the gene, and this may be one of the key links between inflammation and cancer, we just don't know. Clearly it is important for the patient, you, to know how urgent the need for surgery really is, especially with all the pressure upon you right now. The Oncologist will always say "right now, tomorrow." That's why I asked for the pathology data I was trying to help you focus on the key issue with cancer - how quickly is it spreading?
It is not always better to err on the side of caution. Surgery carries considerable risks, especially for Th1 patients. I spend a lot of time explaining to doctors the risks of surgery and hospitalization.
..Trevor..Last edited on Fri Aug 17th, 2007 23:30 by Meg Mangin R.N.
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Meg Mangin R.N.
Research Team
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Posted: Tue Mar 6th, 2007 23:02 |
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(filelink)
Questions on Efficacy Cloud a Cancer Vaccine
Merck Predicts Big Fall In Cervical Lesions,But Data Are Complex
By JOHN CARREYROU
The Wall Street Journal]
April 16, 2007
When Merck & Co. introduced its new vaccine against cervical cancer last June, it gave it one of the biggest pushes any new medicine has received. The company lobbied dozens of states to make the vaccine mandatory for 11- and 12-year-old girls. It aired TV ads featuring young girls skipping rope while reciting the slogan, "I want to be one less" woman to battle the disease.
The campaign scored some big victories. The Centers for Disease Control and Prevention declared all women age 11 to 26 should get the vaccine, called Gardasil. Texas and Virginia passed mandatory-vaccination laws for girls entering the sixth grade. Even after Merck halted its lobbying in February amid criticism, an organization backed by the company continues to push for similar laws, and about 20 states are considering them. The vaccine costs $360 for a three-shot regimen. (See the full CDC recommendations.1)
But behind the scenes, Gardasil has been dogged by uncertainty about how effective it really is. Merck won approval for the vaccine based on research that showed it protected against two strains of the human papillomavirus, known as HPV 16 and 18, that are thought to cause 70% of cervical-cancer cases. The Food and Drug Administration didn't ask its panel of experts advising on Gardasil to rule on whether the vaccine specifically prevented the cancer itself. In clinical trials, 361 of 8,817 women who received at least one shot of Gardasil went on to develop precancerous lesions on their cervixes within three years of vaccination, just 14% fewer than in a placebo control group.
Scott Emerson, a professor of biostatistics at the University of Washington who sat on the FDA advisory committee, says he's not persuaded the vaccine is worth the billions of dollars likely to be spent on it in coming years. "I do believe that Gardasil protects against HPV 16 and 18, but the effect it will have on cervical-cancer rates in this country is another question entirely," says Dr. Emerson. "There is a leap of faith involved."
Merck says the 14% figure is misleading because more than a quarter of the women in the study were already infected with HPV before receiving the vaccine, blunting its effect. Gardasil isn't designed to treat those with pre-existing infection. The company prefers to point to a subset of 4,616 trial participants who were mostly free of HPV when they were vaccinated. Only 52 of these women went on to develop precancerous lesions on their cervixes over the next three years, 46% fewer than among the placebo group. Merck says this smaller group of women is the one most representative of the 11- and 12-year-old girls for whom Texas and Virginia have required vaccination. Merck has a lot riding on Gardasil. It faces patent expirations on other best sellers and legal costs related to Vioxx, the withdrawn painkiller linked to heart attacks and strokes. Some analysts believe Gardasil's annual sales could reach billion or more by 2010.
Work on a cervical-cancer vaccine goes back nearly two decades, after scientists discovered that HPV infection can trigger lesions of the cervix that eventually turn into cancer. In the early-to-mid-1990s, Merck licensed patents held by the National Cancer Institute and CSL Ltd. of Australia, and began work on commercializing the vaccine.
From the start, Merck faced a challenge in winning acceptance of the vaccine as a universal necessity for American women. Though common in developing nations, cervical cancer is a relatively rare disease in the U.S., accounting for about 0.7% of cancer diagnoses and deaths each year. Women already have a highly effective method of prevention: visiting a gynecologist for regular Pap tests. The low-tech exam has contributed to an 80% reduction in cervical-cancer deaths in the U.S. over the past 50 years.
Human studies of the present version of the vaccine, which also targets two HPV strains that cause genital warts, began in 2000. The vaccine was administered to more than 20,000 women. It is delivered in three injections over six months. Merck submitted Gardasil to the FDA for approval in 2005.
Hints of Trouble
A meeting of the FDA advisory panel that reviewed Gardasil in May 2006 gave the first hint of Merck's troubles in persuading doctors of Gardasil's real-world efficacy. In its presentation, Merck stressed the vaccine's nearly 100% effectiveness in blocking infection by HPV 16 and 18 and in preventing precancerous lesions caused by those two strains. But a document prepared for the committee by an FDA reviewer noted the vaccine's limited overall efficacy against precancerous lesions in the broader group of nearly 9,000 trial participants. (]Read the FDA reviewer's document.8)
Dr. Emerson, the University of Washington professor, expressed concern that Merck wasn't putting enough emphasis on the question of whether the vaccine prevented cervical cancer. "It's almost the treating the symptom but not the disease sort of idea," he said, according to a transcript of the meeting. (Read the transcript.9)
Merck pointed to the confounding factors behind the lower efficacy rates, including the problem of women who came into the trial already infected. In an interview, Merck's Dr. Barr says Gardasil's true efficacy will become more apparent with time, particularly in the group that includes women with a pre-existing infection.
While Merck often states that Gardasil prevents infection with viruses that account for 70% of cervical-cancer cases, Dr. Barr concedes that the vaccine is less than 70% effective against precancerous lesions. Merck says this is because the HPV strains not covered by Gardasil cause disproportionately more precancerous lesions that don't end up turning into cancer.
Efficacy against lesions is a significant issue because after a Pap test, doctors generally remove any lesions that reach a certain grade of seriousness, even though some might not turn into cancer. The surgery involves cutting out part of the cervix and can cost several hundred to several thousand dollars. Dr. Barr predicts Gardasil will eventually be shown to prevent nearly 60% of precancerous lesions that doctors would want to remove among women who were free of HPV infection when they were vaccinated.
Ultimately Gardasil received the panel's unanimous approval, and the FDA approved the vaccine in June 2006. The agency reasoned that waiting for more data would prevent some women who needed the vaccine from getting it.
With the FDA's approval, Merck faced a new challenge: persuading the public to take its vaccine. It got a quick boost from the CDC, which issued guidance in late June recommending that all girls receive the vaccine at age 11 or 12. The CDC said women age 13 to 26 should also get the vaccine. Gardasil was also endorsed by the American Academy of Pediatrics.
Merck crafted its advertising and public relations to avoid some of the less-favorable numbers surrounding Gardasil. The TV commercial says the vaccine "may help protect you" from HPV strains "that may cause 70% of cervical cancer." The company doesn't often discuss the lower efficacy against precancerous lesions or in populations where some women are already infected. The "one less" slogan avoids the question of how many lives will be saved.
Some Gardasil supporters funded by Merck are less careful about qualifying their claims. At the FDA advisory committee hearing, Martha Nolan, vice president of a women's health group that receives funds from Merck, said that by approving Gardasil, the agency had "the opportunity to eradicate this terrible disease."
After the FDA approval, a group of female state legislators called Women in Government started a campaign to get states to mandate vaccinations. The group receives money from Merck but won't say how much. Many of the pending bills would allow parents to keep their children out of the vaccination program, but only after submitting proof that they have received information about cervical cancer and the vaccine.
In early January, Women in Government held a conference for some 60 state legislators in Marco Island, Fla., paying for their airfare and hotel rooms. One of the speakers was Christine Baze, a pop singer and cervical-cancer survivor. As she performed songs on the piano, Ms. Baze told the story of her battle with the disease and said she wished a vaccine had been available to her. Ms. Baze says Women in Government paid her a $2,500 fee and covered her travel and lodging. She says she didn't receive any money from Merck for the appearance, but the company has paid her $7,500 to speak at three other events.
Marilyn Canavan, a representative in the Maine assembly who attended the conference, says she was bothered by the large number of drug-industry lobbyists she saw. A list of conference participants shows that 30 pharmaceutical-industry representatives were present -- one for every two state legislators. Merck had two representatives there. Ms. Canavan has since resigned her post as Women in Government's director in Maine over concerns that the group's agenda is being dictated by drug companies. Susan Crosby, Women in Government's president, says those concerns are unfounded.
Other state lawmakers came away from the conference inspired. Upon returning home, Jessica Sibley Upshaw, a representative in the Mississippi assembly, drafted a bill that would make vaccination a school requirement. "For me, it's a common-sense thing to do if we can eradicate a disease," she says. Ms. Upshaw's bill has since died, but she plans to reintroduce it.
Sparking an Uproar
In February, Texas Gov. Rick Perry bypassed the state legislature and issued an executive order mandating that all girls entering the sixth grade be vaccinated as of September 2008. One of Merck's lobbyists in Texas is Mike Toomey, Gov. Perry's former chief of staff, and Merck contributed $6,000 to the governor's re-election campaign. Mr. Toomey didn't return calls and emails seeking comment. A spokeswoman for the governor says he acted to protect the public's health, not because of the contribution or the lobbying of his former aide.
Gov. Perry's order sparked an uproar. Among the opponents are religious conservatives who say receiving the vaccine conflicts with their message of abstinence. Other opponents say Gardasil isn't worth the cost, which includes $360 for the vaccine and up to several hundred dollars more for three doctors' appointments to get the shots. The money would be better spent, these people say, in pushing Pap tests for women who aren't getting them now.
John Schiller, one of the National Cancer Institute scientists whose vaccine work was licensed by Merck, believes Gardasil is an important advance that should receive wide use, but he has mixed feelings about the way the company has promoted it. He hopes it won't divert public-health dollars away from regular Pap screening, which he says remains the most important weapon against cervical cancer. Merck "is a heavy-handed company," Dr. Schiller says. "When they do something, they spare no energy. It's the Merck way or the highway."
Merck says cost-effectiveness studies suggest the vaccine could deliver its life-saving benefits at a reasonable cost, in part by reducing the need for frequent Pap tests. Most of these studies have been funded by Merck and GlaxoSmithKline PLC, maker of another HPV vaccine, Cervarix. Glaxo applied for FDA approval of Cervarix last month.
One skeptic is Diane Harper, a longtime HPV researcher and professor at Dartmouth Medical School, who was involved in Gardasil's clinical trials and has received speaker and consulting fees from Merck and Glaxo. She says as many as 10% of 11- and 12-year-old girls may already have HPV, either from sexual activity, sexual abuse or transmission through nonsexual skin-to-skin contact. That could reduce the vaccine's efficacy, she says.
Dr. Harper also suspects the vaccine may require booster shots after 10 years. Merck says it's not sure how long the vaccine's protection will last and is monitoring women over the long term to find out.
The American Cancer Society, while agreeing with the CDC that girls should be vaccinated, said in January there is "insufficient evidence" that women age 19 to 26 will benefit from the vaccine because many have already been exposed to HPV.
Worried about the backlash that emerged in February in Texas and other states, Merck shifted into damage control. Richard Haupt, Merck's executive director of medical affairs, placed calls to respected figures in the vaccine field, including Jon Abramson, the chairman of the CDC's advisory committee on immunization practices, and Joseph Bocchini, chairman of the committee on infectious diseases at the American Academy of Pediatrics. Both men and others told Dr. Haupt they supported the vaccine, but it was too early and counterproductive to push for school requirements.
On Feb. 20, Merck announced that it was suspending its lobbying push, but Women in Government continues to lobby for school requirements. Virginia's mandate became law two weeks ago.
Write to John Carreyrou at john.carreyrou@wsj.com10
State by State
The following states have introduced legislation on making cervical-cancer vaccinations a school requirement:
State Proposal Status
California
Bill would have required girls entering the sixth grade to be vaccinated.
Withdrawn for further consideration.
Colorado
Bill would require 12-year-old girls to be vaccinated to attend school. Allows parents to opt their daughters out.
Pending
Connecticut
Bill would require girls receive a first dose of the vaccine before entering the sixth grade. Allows parents to opt their daughters out on medical or religious grounds.
Pending
District of Columbia
Bill would require girls to be vaccinated before they turn 13 to attend school. Allows parents to opt their daughters out.
Pending
Florida
Bill would have required 11- and 12-year-old girls to be vaccinated to attend school. Allows parents to opt their daughters out.
Died in committee
Georgia
Bill would require girls entering the sixth grade to be vaccinated unless parents can't afford the vaccine or object to it on medical or religious grounds.
Pending
Illinois
Bill would require girls entering the sixth grade to be vaccinated. Allows parents to opt their daughters out.
Pending
Kansas
Bill would require girls entering the sixth grade to be vaccinated. Allows parents to opt their daughters out on medical or religious grounds.
Pending
Kentucky
Bill would require girls entering middle school to be vaccinated. Allows parents to opt their daughters out.
Passed House, to Senate
Maryland
Bill would have required girls entering the sixth grade to be vaccinated.
Withdrawn
Massachusetts
Bill would require girls entering the sixth grade to be vaccinated. Allows parents to opt their daughters out on religious grounds.
Pending
Michigan
Bill would require girls entering the sixth grade to be vaccinated. Allows parents to opt their daughters out.
Pending.
Missouri
Bill would require girls entering the sixth grade to be vaccinated. Allows parents to opt their daughters out on medical or religious grounds.
Pending
Minnesota
Bill would require 12-year-old girls to be vaccinated to attend school. Allows parents to opt their daughters out.
Pending
Mississippi
Bill would have required girls entering the sixth grade to be vaccinated.
Died. Sponsor planning to re-introduce it with an opt-out clause.
New Jersey
Bill would require girls in grades seven through 12 to be vaccinated. Allows parents to opt their daughters out on medical or religious grounds.
Pending
New Mexico
Bill would require nine- to 14-year-old girls to be vaccinated to attend school. Allows parents to opt their daughters out.
Passed legislature. Vetoed by governor.
Ohio
Bill would require girls entering the sixth grade to be vaccinated. Allows parents to opt their daughters out.
Pending
Oklahoma
Bill would require girls entering the sixth grade to be vaccinated.
Pending
South Carolina
Bill would require girls entering the seventh grade or 11 years of age to be vaccinated. Allows parents to opt their daughters out on medical or religious grounds.
Pending
Texas
Governor issued executive order requiring that girls entering the sixth grade be vaccinated. Allows parents to opt their daughters out.
Bill overriding the executive order has passed the House and is pending in the Senate.
Vermont
Bill would require girls entering the sixth grade to be vaccinated. Allows parents to opt their daughters out on medical, moral or religious grounds.
Pending
Virginia
Bill requires girls entering the sixth grade to be vaccinated. Allows parents to opt their daughters out.
Passed the legislature. Goes into effect Oct. 1, 2008; to be implemented in fall of 2009.
West Virginia
Bill would require girls entering the sixth grade to be vaccinated. Allows parents to opt their daughters out on medical grounds.
Pending
Source: National Conference of State Legislatures, state legislatures
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Meg Mangin R.N.
Research Team
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Posted: Fri Jun 15th, 2007 21:36 |
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(filelink)
Winning the (propaganda) war on cancer
Where do you bury the survivors?
By Thomas C. Greene in Dublin
Originally Published in 'The Register', Jun 15, 2007, (Copyright The Register 2007).
"But, yes, the UK's cancer survival rates have doubled in 30 years. That certainly is true. Are cancer patients living twice as long? Certainly not. Some of the increase is due solely to the fact that early diagnosis improves survival numbers independent of mortality"
A couple of years ago, the American Cancer Society gaily reported that cancer survival rates have been improving dramatically and steadily. A few weeks ago, Cancer Research UK announced a similarly sunny prognosis for the public at large: UK survival rates have doubled in 30 years. Yes, we are all "surviving" longer with cancer, the experts can assure us.
What fabulous news this seems to be: people diagnosed today are twice as likely to survive for 10 years than people diagnosed 30 years ago. As the press release says: "While survival varies widely between different types of cancer, on average, a patient with cancer now has a 46.2 per cent chance of being alive 10 years after diagnosis. This compares with 23.6 per cent 30 years ago".
Now, what do you suppose that means? Do you imagine that treatments have improved so much in 30 years that we are actually able, on average, to slow the disease's rate of progress by half? That we have actually doubled the life expectancy of cancer patients? That certainly is one message that we might take from the press release.
Well, those who actually bother to read medical literature know that what is being claimed here is a bit less fabulous than that. In the field of medicine, words like "survival" and "cure" are professional jargon with specific meanings and implicit qualifications. Researchers and doctors know what these terms mean, and they use them very carefully, assuming the implied qualifications are understood. Unfortunately, you and I might understand something quite different from what is meant.
So, what do professionals mean when they speak of survival? Typically, they speak of five-year survival in a way that gives patients a decent guess of their chance of still breathing five years after diagnosis. The doctor considers the specific form of cancer, its state of progress at the time of diagnosis, the patient's overall health, age, sex, and numerous other factors, and then a comparison is made between the individual patient and a group of similar patients.
So, it's common for a practitioner to compare your current condition to a large group of others previously diagnosed in similar circumstances, and tell you, for example, that among those similar to you when they were diagnosed, 60 per cent survived for five years.
Thus you would have a 60 per cent chance of surviving for five years. You might also be told that you have, say, a 30 per cent chance of surviving disease free (i.e., in remission), and a 45 per cent chance of surviving progression free (disease is detectable but not worsening), for five years, based on comparisons with others whose conditions were similar to your own at the time of diagnosis. Thus, "survival", in the professional sense, is relative.
But if survival is a relative measure, what can it mean when Cancer Research UK says that survival rates have improved overall? What, exactly, is being compared to what in that case? Does it mean that we have got so good at treating cancer that the disease typically progresses at half the rate it once did? Does it mean that patients are actually living twice as long as they did 30 years ago? I do wish I could say this is so, but then I would tell a lie.
A meaningless boost
Repeatedly, we are reminded that early diagnosis and early treatment are major reasons for the improvement. We have better diagnostic tools and screening methods than ever before; more mass screenings for the public are scheduled, often by charities serving populations with poor health services; family practitioners are more aware of the disease and its early symptoms; and more patients are now aware of the symptoms that might warrant a trip to the quack. Of course, the treatments themselves have improved as well, and this certainly is having some effect.
However, the item that we need to question most carefully is the effect of early diagnosis and early treatment. Treatments are starting earlier these days, and we are all "surviving" longer with cancer. But just how fabulous is that news, really?
The cancer treatment industry desperately wants us to think it's beyond fabulous: cancer drugs, and related diagnostic and treatment devices, are among the most expensive, and most profitable, known to medicine. There are those who profit from our assumption that early diagnosis and treatment extend patients' lives. And profit they do: think of the hospitals, drug makers, device makers, diagnostic technicians, radiotherapists, surgeons, and oncologists. Cancer treatment is a vast, complex industry, and like any industry it flourishes best in a field of semi-educated consumers.
And so we are subtly shepherded toward the belief that our deaths from cancer will be postponed significantly because of early, and very costly, medical intervention.
Unfortunately, this is not always easy to prove. And the word "survival" itself is tricky, and normally used in a relative context, as mentioned previously. Indeed, you can "survive" longer than another patient with the same cancer, but not actually live any longer, because the survival clock starts running on the day of diagnosis. Thus, everyone who is diagnosed early automatically survives longer, independent of any other variable. Conversely, if you are diagnosed late, you are not going to "survive" for long, although you might already have lived for quite a long time with your cancer.
So it is hardly time to break out the noise makers and Champagne merely because the survival numbers have doubled. Let's go to an illustration: imagine a doctor with a patient who has got Stage IV (metastatic) cancer at the time of diagnosis. Now, one might ask the doctor a few questions, such as, how long did the patient take to progress from Stage I to Stage IV? Or, just when did carcinogenesis actually occur - six months ago? Six years ago?
Of course, no one can say with certainty; patients are individuals, and diseases work differently in different people (as do drugs and other treatments, by the way). But because our example patient is diagnosed at Stage IV, we'll learn only how long the disease needs to kill them when treatment starts at that point.
Now, compare this to a patient with the same disease, only Stage II at the time of diagnosis. If there is good treatment and follow-up, we'll get a detailed picture of how long the disease needs to kill this early-treatment patient. But because we don't know the late-treatment patient's disease history, we can't say much about how long that patient has lived with their cancer, and thus it is difficult to compare the progress of these two hypothetical patients.
Did the Stage IV patient progress faster from Stage I than the early-treatment patient did? We might assume that they did, but we don't really know. Indeed, their own body might have fought the disease well, and they might possibly have lived longer with untreated cancer than the early-treatment patient lived with treated cancer. This might be unlikely, but the uncertainty here is nonetheless real.
Oncologists who see hundreds of patients over the years will get a sense of the disease's natural progress, and should be able to say with some confidence that when this or that type of cancer is left untreated, it usually progresses a lot faster than it does when it's treated. And that instinctive sense, learned from experience and observation, is probably reliable, although it should be noted that it isn't proof.
Handy assumptions
Among professionals, jargon like "survival" can be useful; it is generally used correctly, among others who will interpret it correctly. And yes, we can learn from studies where these terms are in play. We can certainly compare treatments among groups of early-treatment patients and see if one regimen is better than another, using five-year survival as a context. We can also compare late-treatment patients to early-treatment patients who have arrived at the same late stage, and see if early treatment has provided an edge in survival from that point forward.
But the idea that early treatment inevitably causes a patient to live longer is not always proven. Treatments make tumours stop growing, or shrink, or even go away. This is not the same as saying that the patients die significantly later than they otherwise would. We want to believe this, and there are people and corporations with an interest in encouraging us to believe it, but it is, as I said, very tricky to prove in some cases.
Now, here is a discouraging observation: there certainly are occasional breakthrough treatments, but generally, when we compare different regimens, we rarely see a dramatic difference in effectiveness among study groups, which suggests that the treatments probably aren't doing as much as we've been led to believe. Especially in the difficult cases.
Let's consider a few of the really tough cancers: stomach, pancreatic, lung, ovarian: these have very poor survival rates and treatment is usually not very effective. Why? Because symptoms rarely show until the disease is well advanced and metastatic. Catching one of these cancers early is usually a matter of luck.
Generally, there is little luck to speak of when you are diagnosed with one of these cancers. Your oncologist sits you down and gives you "the talk". It's advanced and spreading; we're going to do all we can; there are treatments and we will explore all the options; we learn more every day about treating this disease, etc. But you know that with a late diagnosis, there won't be a great deal of time before you die, and you think, my God, if only it could have been caught earlier: I would be able to live longer. You've heard all the glowing rhetoric about early diagnosis and early treatment, and you feel cheated of your chance to really fight the disease, and cheated of the most valuable thing of all: time to live.
But this might be total nonsense, and you might be suffering additional anguish for no reason. You see, with a late diagnosis, your survival is going to be short, but your life might not be much shorter than it would be if you'd been diagnosed early. As we discussed previously, you might already have survived quite a long time with your cancer; you simply haven't been aware of it. There is no reason to believe that you are not already an impressive cancer survivor.
Unfortunately, few patients will feel this way, and this is an incredibly cruel consequence of the survival propaganda that the media and medical industry disseminate.
Furthermore, to be "cured" of cancer usually means that you are in remission five years after diagnosis. So here's another problem: early diagnosis automatically increases the rate of so-called "cures", just as it automatically increases the rate of survival, independent of any other variable.
Personally, I think the notions of "survival" and "cures" should be abolished from public discourse, and should remain in the realm of research and treatment, where they are useful. Instead of five-year survival, patients and the public at large should be talking about mortality. "Has this treatment been shown to impede the disease's progress and delay death?" That really is the only question we should be asking, at least in the context of cancer survival (certainly there are other legitimate goals for treatments, such as palliative care, etc).
And as for "cures", this nonsense needs to be replaced with honest language as well: in the public sphere, "cured" should not be permitted to mean anything other than, "the patient died from a different cause". If you come out of your oncologist's office with a new diagnosis, and absent-mindedly step into the path of a city bus, well, that bus will cure your cancer. The fatal heart attack you have a month later will certainly cure your cancer. But, outside the context of medical research and calculating a patient's odds, it is preposterous to speak of a "cure" unless something else brings about your death.
This linguistic sloppiness makes it very difficult for us, as consumers of medical products and services, to know if early diagnosis and intervention do significantly more than enrich the medical industry. Certainly there are tumours that can be detected early, and when diagnosed at Stage I (in situ), may often be removed surgically and then legitimately called cured, because many patients with such experiences do in fact end up dead from other causes.
But there are other cancers that are extremely difficult to treat, and - if we were to dispense with the linguistic vagueness - are probably close to 100 per cent incurable, with very high (i.e., rapid) mortality rates. We might as well face the facts. But we cannot face them when journalists and interested parties fuel public debate with professional jargon that is often misinterpreted outside the medical industry.
If we in the press were to chuck "survival" and report on cancer mortality instead, and save "cure" for those who die of something other than cancer, the public might learn a few things that the industry would prefer them to remain foggy about. As patients, we might begin asking whether an expensive regimen has actually been shown to extend lives. As charitable donors, we might begin asking if our money is going into dead-end research where virtually no mortality advantage has ever been found - and whether it might be better spent on public screening programmes, or prevention initiatives, or better palliative care.
But, yes, the UK's cancer survival rates have doubled in 30 years. That certainly is true. Are cancer patients living twice as long? Certainly not. Some of the increase is due solely to the fact that early diagnosis improves survival numbers independent of mortality. Yes, some of the increase is due to improved treatment regimens, and to the fact that early treatment can improve mortality rates - at least to some degree, and at least for some patients. But how much, and for how many? Well, that is the question. So here's an idea: why don't we in the press start using language that helps people to answer it?
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Meg Mangin R.N.
Research Team
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Posted: Mon Jun 18th, 2007 16:41 |
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(filelink)
Treatment may fuel cancer's spread, study finds
By Maggie Fox, Health and Science Editor
WASHINGTON (Reuters) - Treating cancer with surgery, chemotherapy or radiation may sometimes cause tumors to spread and U.S. researchers said on Thursday they may have nailed down one of the causes -- a compound called TGF-beta.
Tests in mice show that using the chemotherapy drug doxorubicin or radiation both raised levels of TGF-beta, which in turn helped breast cancer tumors spread to the lung.
But using an antibody to block TGF-beta stopped the process, Dr. Carlos Arteaga and colleagues at Vanderbilt University in Tennessee reported.
Developing drugs that block TGF-beta might help prevent cancer from recurring, Arteaga's team reports in the May issue of the Journal of Clinical Investigation.
"The repopulation and progression of tumors after anti-cancer therapy is a well-recognized phenomenon," the researchers wrote. "It has been shown to occur following radiotherapy, chemotherapy, and surgery."
Cancer experts have wondered if the so-called primary tumor -- the first and biggest tumor -- might somehow suppress the growth of other tumors, and that removing or destroying the first tumor might allow other, undetectable, tumors to then grow.
TGF-beta, which is involved in both the growth and suppression of tumors, may hold part of the answer, Arteaga's team said.
When mice infected with human breast cancer cells were treated with radiation or doxorubicin, they had higher levels of TGF-beta in their blood. They also had more tiny tumor cells in their blood, and these cells metastasized, or spread, to the lungs.
When the mice were treated with an antibody that suppresses TGF-beta, the spread stopped. And this spreading process did not occur at all in mice bred to lack the TGF-beta protein.
"We wondered then if TGF-beta induced by anti-cancer therapies can serve as a survival signal for tumor cells, thus allowing them to withstand therapy and later recur," Arteaga said in a statement.
His team is now testing TGF-beta levels in the blood of breast cancer patients.
"We'll be looking to see in what proportion of patients the serum and tumor TGF-beta goes up, and whether the increase correlates with the inability of the therapy to eliminate the cancer in the breast," Arteaga said.
Higher levels of TGF-beta after treatment may be a way to predict which patients are likely to have their cancer come back after treatment, Arteaga said.
His team is also testing drugs that interfere with TGF-beta to see if they improve survival.
"It probably isn't just TGF-beta that is having this effect," Arteaga said. Many other compounds, including some immune system signaling chemicals, are also associated with tumor spread and growth.
"TGF-beta may be just the tip of the iceberg," Arteaga said.
======================================
This is a murine model, which can lead to errors, but it is generally in agreement with the pathogenic description I have been developing:
1. Cancer starts in inflamed tissue
2. Cancer needs certain Th1 cytokines (eg ICAM) to feed proliferation
3. A healthy immune system will be able to clean up cancerous cells before they can take hold
4. Many cancers are misdiagnosed high-grade inflammation
5. Treatment of this high-grade inflammation with standard cancer therapies may well lead to the development of 'true' cancer
..Trevor..Last edited on Mon Jun 18th, 2007 17:16 by Meg Mangin R.N.
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Meg Mangin R.N.
Research Team
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Posted: Sun Nov 25th, 2007 02:34 |
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[filelink]
Colorectal cancer
Transition from polyp to cancer age-dependent
NEW YORK (Reuters Health) - Men and women with advanced colorectal polyps have a similar risk of progressing to colorectal cancer (CRC) and the risk increases with age in both sexes, according to a study conducted in Germany.
Colorectal polyps (also called adenomas) are found in up to 40 percent of adults over 50. Fewer than 5 percent of them turn cancerous.
To come up with age- and sex-specific estimates of transition rates from advanced polyps to CRC, Dr. Hermann Brenner from the German Cancer Research Center, Heidelberg and colleagues used combined data from 840,149 screening colonoscopies and from national population-based cancer registries.
They report in the journal Gut that annual transition rates increase from 2.6 percent in women aged 55 to 59 years to 5.6 percent in women aged 80 and older. For men in these age groups, transition rates increase from 2.6 percent to 5.1 percent.
In their analyses, estimates of 10-year cumulative risk increased from 25.4 percent at age 55 years to 42.9 percent at age 80 years in women, with corresponding increases from 25.2 percent to 39.7 percent in men.
"Our finding that advanced adenoma transition rates are strongly age-dependent could have important clinical implications, possibly including a higher age at first screening or differential endoscopy intervals according to age," Brenner and colleagues write.
"However, additional risk factors, such as family history of CRC, also have to be taken into account," they note.
SOURCE: Gut, November 2007.
Folic Acid Linked To Increased Cancer Rate, Historical Review Suggests
ScienceDaily (Nov. 5, 2007) — Two recent commentaries appearing in Nutrition Reviews find that the introduction of flour fortified with folic acid into common foods was followed by an increase in colon cancer diagnoses in the U.S. and Canada.
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Meg Mangin R.N.
Research Team
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Posted: Sat Dec 15th, 2007 16:56 |
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[filelink]
ScienceDaily (Nov. 19, 2007)
Immune System Can Drive Cancer Into Dormant State
A multinational team of researchers has shown for the first time that the immune system can stop the growth of a cancerous tumor without actually killing it.
Scientists have been working for years to use the immune system to eradicate cancers, a technique known as immunotherapy. The new findings prove an alternate to this approach exists: When the cancer can't be killed with immune attacks, it may be possible to find ways to use the immune system to contain it. The results also may help explain why some tumors seem to suddenly stop growing and go into a lasting period of dormancy.
"Thanks to the animal model we have developed, scientists can now reproduce this condition of tumor dormancy in the laboratory and look directly at cancer cells being held in check by the immune system," says co-author Robert Schreiber, Ph.D., Alumni Professor of Pathology and Immunology at Washington University School of Medicine in St. Louis. "That will allow us to see if we can model this state therapeutically."
The study's authors call the cancer-immune system stalemate equilibrium. During equilibrium, the immune system both decreases the cancer's drive to replicate and kills some of the cancerous cells, but not quickly enough to eliminate or shrink the tumor.
"We may one day be able to use immunotherapy to artificially induce equilibrium and convert cancer into a chronic but controllable disease," suggests co-author Mark J. Smyth, Ph.D., professor of the Cancer Immunology Program at the Peter McCallum Cancer Centre in Melbourne, Australia. "Proper immune function is now appreciated as another important factor in preventing the development of some cancers. Further research and clinical validation of this process may also turn established cancers into a chronic condition, similar to other serious diseases that are controlled long-term by taking a medicine."
Scientists first proposed that the immune system might be able to recognize cancer cells as potentially harmful more than a century ago. Under a theory that came to be called cancer immunosurveillance, researchers suggested that if this recognition took place, the immune system would attack tumors with the same weapons it uses to eliminate invading microorganisms. Current immunotherapy efforts use therapeutic agents to increase the chances that the immune system will recognize and attack tumors.
But cancer immunosurveillance has been controversial. The theory had begun to fall out of favor over the years, and in 2001, Schreiber, graduate students Vijay Shankaran and Gavin Dunn, and Lloyd Old, M.D., director of the New York branch of the Ludwig Institute for Cancer Research, proposed a major revision. They called their new model cancer immunoediting.
Like the older theory, cancer immunoediting suggests that conflict between cancers and the immune system naturally takes place but proposes that three very different outcomes can result. The immune system can eliminate cancer, destroying it; the immune system can establish equilibrium with cancer, checking its growth but not eradicating it; or the cancer can escape from the immune system, likely becoming more malignant in the process.
Until this latest study, evidence for the second outcome was lacking. Schreiber, Smyth and their colleagues posited equilibrium's existence mainly on the basis of other doctors' clinical experiences. Examples included cancers that inexplicably go into remission for years. In addition, there have been hints that in a few cases organ transplants have transferred undetected dormant tumors to the recipients.
To directly observe dormant tumors in mice, researchers injected them with small doses of a chemical carcinogen. Mice that developed outright tumors were set aside; the remaining mice had small, stable masses at the site of the injections. When certain components of these animals' immune systems were disabled, the small growths became full-blown cancers, suggesting that the immune system had previously been holding the tumors in check.
"We don't think the immune system has evolved to handle cancers," Schreiber notes. "Cancer is typically a disease of the elderly, who have moved beyond their reproductive years, so there probably was no evolutionary pressure for the immune system to find a way to fight cancer."
Schreiber, Smyth and Old speculate that from the immune system's point-of-view, a cancerous cell may look like a cell infected by an invading microorganism. To overcome the safeguards that prevent the immune system from attacking the body's own tissues, the tumor has to have a high level of immunogenicity, or ability to provoke an immune reaction. Cancer cells can reduce their immunogenicity by changing the materials they present to the immune system to more closely resemble those presented by normal tissue. This enables the third outcome of the immunoediting theory: escape.
Equilibrium sometimes may be a more common outcome of tumor-immune encounters than elimination. According to the researchers' theory, some of us may harbor dormant tumors that either developed spontaneously or from exposure to carcinogens. They propose that these quiescent tumors are unleashed only as we age or are exposed to environmental, infectious or physical stresses that cause a breakdown of the immune system.
To follow up, researchers plan a molecular-level investigation of what happens in tumors and the immune system during equilibrium. They also want to test their results' applicability both in humans and in different types of cancers.
"For example, we need to look at which tissues are regularly edited by the immune system and at how closely the immune system watches over these tissues," Schreiber says. "If you completely knock out the immune system in mice, you'll see tumors spring up in some tissues but not in others, and this suggests that there may be differing levels of immune system monitoring in different tissue types."
"Over the past decade, remarkable advances have been made in our understanding of how the immune system reacts against cancer and influences the course of the disease, and defining the equilibrium phase of cancer immunoediting represents the newest milestone in these advances," says Old. "The challenge now is to incorporate these findings into our thinking about human cancer and to develop immunotherapeutic strategies that complement current methods of cancer treatment."
Journal reference: Koebel CM, Vermi W, Swann JB, Zerafa N, Rodig SJ, Old LJ, Smyth MJ, Schreiber RD. Adaptive immunity maintains occult cancer in an equilibrium state. Nature, 2007. Advance online publication (10.1038/Nature 06309)
Funding from the National Cancer Institute, the Ludwig Institute for Cancer Research, the Cancer Research Institute, the Atlantic Philanthropies, and the National Medical Research Council of Australia supported this research.
Adapted from materials provided by Washington University School of Medicine.
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