Cancer

http://www.sciencedaily.com/releases/2009/02/090204172437.htm

Several researchers have observed that the Vitamin D ReceptorA nuclear receptor located throughout the body that plays a key role in the innate immune response. (VDRThe Vitamin D Receptor. A nuclear receptor located throughout the body that plays a key role in the innate immune response.) becomes inactive in cancer patients at just the time when it should be most active.¹ The VDR plays a key role in innate immunityThe body's first line of defense against intracellular and other pathogens. According to the Marshall Pathogenesis the innate immune system becomes disabled as patients develop chronic disease., transcribing thousands of genes² including the genes necessary for several antimicrobial peptidesBody’s naturally produced broad-spectrum antibacterials which target pathogens. as well as the gene, tumor metastasis suppressor protein.

The relationships and mechanisms through which infection and inflammationThe complex biological response of vascular tissues to harmful stimuli such as pathogens or damaged cells. It is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue. increase cancer risk and promote tumor development were recently reviewed (Karin and Greten, 2005). It is well established that chronic infections with hepatitis B and C viruses (HBV, HCV) represent major risk factors for development of hepatocellular carcinoma (HCC), while chronic H. pylori infection is the major risk factor for gastric cancer (Kuper et al., 2000). It was proposed that in both cases and others the infectious agent leads to activation of NF-κB in myeloid cells (and eventually in lymphoid cells), resulting in production of growth and survival factors that stimulate tumor progression and development (Karin and Greten, 2005). Interestingly, HCV was recently found to encode a nonstructural protein (NS5A) that actually inhibits the activation of NF-κB by TNF-α and, as a result, potentiates TNF-α-induced JNK activation (Park et al., 2003). Another HCV protein, NS3/4A, is a protease that cleaves TRIF and Cardif, thereby preventing IKK activation and induction of antiviral innate immunity (Meylan et al., 2005). Importantly, inhibition of NF-κB activation in hepatocytes, the cells that are infected by HCV, was found to increase their susceptibility to carcinogen-induced death (Maeda et al., 2005b) However, hepatocyte death also triggers through inflammation-propagated mechanisms the compensatory proliferation of surviving hepatocytes. The latter depends both on JNK activation within hepatocytes (Maeda et al., 2005b) and on production of proinflammatory cytokinesAny of various protein molecules secreted by cells of the immune system that serve to regulate the immune system., such as TNF-α and IL-6, by inflammatory cells (Fausto, 2000). It thus seems that HBV and HCV infections, for instance, stimulate the development of HCC through both nonspecific injury caused by the cytolysis of virally-infected hepatocytes and through expression of specific proteins that alter the balance between TNF-α-triggered survival and death pathways. The necrotic death of hepatocytes is likely to cause acute activation of liver myeloid cells (Kupffer cells), thereby stimulating the production of growth factors that trigger the compensatory proliferation of surviving hepatocytes, which otherwise spend most of their life in the Go phase of the cell cycle. Compensatory hepatocyte proliferation results in propagation of oncogenic mutations, induced by exposure to exogenous or endogenous carcinogens, leading to clonal expansion of transformed cells that eventually give rise to HCC. As in other inflammatory diseases, chronic viral hepatitis eventually results in persistent activation of inflammation-maintaining T cells (Chisari and Ferrari, 1995). Such T cells can induce the development of HCC when transferred to naive mice. Thus, even in cancer, especially HCC, one can invoke the general model of repeated tissue injury associated with chronic exposure to a pathogen, resulting in acute and then sustained chronic inflammation as the major mechanism underlying the development of a long-lasting chronic disease. Recent work on a mouse model of gastric cancer suggests that repeated tissue injury caused by bacterial infections (in this case caused by a relative of H. pylori—H. felis) is associated with an aberrant regenerative response that may account for this type of cancer as well (Houghton et al., 2004). Given the well-established tumor-promoting function of chronic inflammation (Karin and Greten, 2005) and the requirement of tumor promotion for enhancing cancer development after carcinogen exposure, it is not too farfetched to suggest that chronic airway inflammation caused by repeated exposure to irritants found in tobacco smoke, which enhance exposure to airborne microbes and viruses, plays an important tumor-promoting function in the development of lung cancer as well. http://dx.doi.org/10.1016/j.cell.2006.02.016

Expression and activity of vitamin D receptor in the human placenta and in choriocarcinoma BeWo and JEG-3 cell lines.

Pospechova K, Rozehnal V, Stejskalova L, Vrzal R, Pospisilova N, Jamborova G, May K, Siegmund W, Dvorak Z, Nachtigal P, Semecky V, Pavek P. Department of Biological and Medical Science, Charles University in Prague, Faculty of Pharmacy in Hradec Kralove, Heyrovsky, Hradec Kralove, Czech Republic. Vitamin D receptor (VDR) regulates the expression of many genes involved in mineral metabolism, cellular proliferation, differentiation and drug biotransformation. We studied the expression and activity of VDR and its heterodimerization partner retinoid X receptor-alpha (RXRalpha) in choriocarcinoma trophoblast cell lines BeWo and JEG-3, in comparison with human isolated placental cytotrophoblasts and human full term placenta. We found that VDR and RXRalpha are localised in the human term placenta trophoblast and expressed in isolated cytotrophoblasts. However, we found low expression and no transcriptional activity of VDR in used choriocarcinoma cell lines. The inhibitor of DNA methylation, 5-deoxy-3'-azacytidine, and histone deacetylase inhibitor sodium butyrate partially restored the expression of VDR, suggesting an epigenetic suppression of the gene in choriocarcinoma cells. Differentiation of BeWo cells resulted in up-regulation of VDR mRNA. Finally, we observed a non-genomic effect of 1,25(OH)(2)D(3) in the activation of the extracellular signal-regulated kinase (ERK) signalling pathway in JEG-3 cells. In conclusion, our results suggest an epigenetic repression of VDR gene expression and activity in choriocarcinoma cell lines, and a non-genomic effect of 1,25(OH)(2)D(3) in JEG-3 cells. PMID: 19133314

Both high and low levels of blood vitamin D are associated with a higher prostate cancer risk: a longitudinal, nested case-control study in the Nordic countries.

Tuohimaa P, Tenkanen L, Ahonen M, Lumme S, Jellum E, Hallmans G, Stattin P, Harvei S, Hakulinen T, Luostarinen T, Dillner J, Lehtinen M, Hakama M. Medical School, University of Tampere, Tampere, Finland. Pentti.Tuohimaa@uta.fi Vitamin D inhibits the development and growth of prostate cancer cells. Epidemiologic results on serum vitamin D levels and prostate cancer risk have, however, been inconsistent. We conducted a longitudinal nested case-control study on Nordic men (Norway, Finland and Sweden) using serum banks of 200,000 samples. We studied serum 25(OH)-vitamin D levels of 622 prostate cancer cases and 1,451 matched controls and found that both low (</=19 nmol/l) and high (>/=80 nmol/l) 25(OH)-vitamin D serum concentrations are associated with higher prostate cancer risk. The normal average serum concentration of 25(OH)-vitamin D (40-60 nmol/l) comprises the lowest risk of prostate cancer. The U-shaped risk of prostate cancer might be due to similar 1,25-dihydroxyvitamin DPrimary biologically active vitamin D hormone. Activates the vitamin D nuclear receptor. Produced by hydroxylation of 25-D. Also known as 1,25-dihydroxycholecalciferol, 1,25-hydroxyvitamin D and calcitirol.(3) availability within the prostate: low vitamin D serum concentration apparently leads to a low tissue concentration and to weakened mitotic control of target cells, whereas a high vitamin D level might lead to vitamin D resistance through increased inactivation by enhanced expression of 24-hydroxylase. It is recommended that vitamin D deficiency be supplemented, but too high vitamin D serum level might also enhance cancer development. Copyright 2003 Wiley-Liss, Inc. PMID: 14618623

L-form bacteriaDifficult-to-culture bacteria that lack a cell wall and are not detectable by traditional culturing processes. Sometimes referred to as cell wall deficient bacteria. may be responsible for at least part of the pathogenesis of cancer. For one thing, L-form bacteria have been found in the tissues of patients with cancer. Some studies have found that people with certain types of cancer, such as prostate cancer, display the same dysregulated vitamin D metabolism observed in people with other chronic diseases now known to be bacterial in origin.

A photo taken by Cantwell showing L-formsDifficult-to-culture bacteria that lack a cell wall and are not detectable by traditional culturing processes. Sometimes referred to as cell wall deficient bacteria. of various inside the cells of a patient with breast cancerL-forms of various shapes and sizes inside the cells of a patient with breast cancer, photo taken by Alan CantwellSeveral forms of bacteria have already been linked to cancer. Researcher Alan Cantwell used acid-fast staining to identify L-form bacteria in patients with Hodgkin’s Disease, lymphoma, prostate cancer and other immunological diseases. Both gastric cancer and gastric MALT lymphoma (lymphoma of the mucosa-associated lymphoid tissue) have been associated with H. pylori bacteria, and the bacterium has been categorized as a group I carcinogen by the International Agency for Research on Cancer (IARC).¹¹

Other research has shown a link between a cancer of the eye, ocular adnexal lymphoma (OAL) and Chlamydia bacteria. In October, researchers at the San Raffaele H. Scientific Institute in Milan published, in Journal of the National Cancer Institute, the results of a study which demonstrated that the antibiotic doxycycline is proving to be an effective treatment for this form of cancer. “Our prospective trial revealed that doxycycline is a fast, safe, and active treatment for OAL, both at initial diagnosis and at relapse,” the study’s authors wrote.¹²

In 2006, D.L. Mager and team published a review article in the Journal of Translational Medicine called, “Bacteria and Cancer: Cause, or Cure?” According to Mager, “An overwhelming body of evidence has determined that relationships among certain bacteria and cancers exist.” In the paper, Mager details how research teams around the world have implicated Salmonella typhi in gallbladder cancer, Streptococcus bovis and E.coli in colon cancer, and Chlamydia pneumoniae in lung cancer. According to Mager, the mechanisms by which bacterial agents may induce carcinogenesis include “chronic infection, immune evasion, and immune suppression.”¹³

This suggests that, just as in other chronic diseases, long-term supplementation with vitamin D slows the immune system and facilitates the proliferation of L-form bacteria, ultimately driving the progression of cancer. Over time, L-form bacteria release more cytokines into the tissues, resulting in elevated levels of inflammation.

“Everybody knows inflammation induces cancer”, stated Francesco Marincola, MD, Senior NIH Investigator, at a recent conference. But how? According to biomedical researcher Trevor Marshall, “Th1 inflammationThe complex biological response of vascular tissues to harmful stimuli such as pathogens or damaged cells. It is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue. feeds the initial proliferative stage of cancer. Without Th1 inflammation the cancer cells can’t get adhesion to the ‘healthy’ cells and tissues, and can’t become proliferative. Then, as the cancer starts to metastasize, the inflamed stem cells are critical in enabling the spread of the inflammation, and the metastasis of the cancer.”

Furthermore, the Vitamin D Receptor is known to transcribe genes that work to prevent the spread of cancer. These include Metastasis Suppressor Protein, a protein that slows the creation of cancer cells, and Mitochondrial Tumor Suppressor 1 gene. But when too much 25-DThe vitamin D metabolite widely (and erroneously) considered best indicator of vitamin D "deficiency." Inactivates the Vitamin D Nuclear Receptor. Produced by hydroxylation of vitamin D3 in the liver. and bacterial proteins bind and inactivate the Vitamin D Receptor these anti-cancer genes are not transcribed correctly.

Because inflammation induces cancer, it’s no surprise that research teams who follow their subjects for only a few years find that vitamin D seems to be “preventing” cancer. What they actually pick up on is the temporary decrease in cytokineAny of various protein molecules secreted by cells of the immune system that serve to regulate the immune system. production that results when 25-D slows the immune system and less L-form bacteria are killed. In the short term, as less bacteria die, less cytokines are released into the tissues, resulting in a temporary decrease in inflammation.

But in the long run, L-form bacteria will take full advantage of the subjects’ weakened immune systems. The bacteria will increase in number and spread to new tissues and organs. Decades later, the subjects will display higher levels of inflammation and higher rates of cancer and/or other chronic diseases, because even consistent immunosupression with vitamin D will no longer sufficiently prevent so many L-form bacteria, both alive and dead, from releasing cytokines into the tissues. Consequently, researchers who follow their study participants for the longest periods of time are often the ones to claim that supplementation with vitamin D offers no benefit when it comes to fighting the cancer.

Is cancer just an incurable infectious disease?

Broxmeyer L. 148-14A Eleventh Avenue, Whitestone, NY 11357, USA. medamerical@cs.com The word 'cancer' is of Latin derivation and means crab. By the turn of the 20th Century organized medicine had come to the conclusion that it was not a matter of whether infectious disease caused cancer, but which one. For over two hundred years a cancer germ had been discovered and rediscovered, named and renamed, each scientist adding to the knowledge, but to no avail. Then, in 1910, certain American medical powers did a 180-degree rotation, deciding that cancer was not caused by a microbe, and that anyone who thought otherwise was a heretic, a charlatan or a quack. But Dr. Virginia Livingston and her network were none of the above, their meticulous peer-reviewed research and publications, done at the height of US post World War II technology. And Dean Burk, Head of Cell Chemistry at the NCI went so far as to say that Livingston's cancer germ was as real and certain as anything known about cancer. Researcher, MD Alan Cantwell Jr. grew up thinking that all germs responsible for the important diseases were supposed to have already been discovered. But much to his dismay, he found one that was left out: the cancer germ. Cantwell already knew that for finding this, Livingston had already been branded by traditional medicine, leaving what he thought to be perhaps the major discovery of the 20th century largely discredited. The striking analogy between cancer and tuberculosis was noticed long before the tubercle bacillus was discovered. In 1877, Sir John Simon clearly pointed out the similarity and in fact argued very strongly in favor of a microbial origin for cancer. But Simon's vindication would have to wait for Livingston's germ, which although tuberculosis-like, was not tuberculosis but an atypical form of this mycobacterium, melded from the mycobacterium and other related Actinomycetales. Had medical science and the powers that be spent as much time in investigating and destroying Livingston's germ as they did in attacking her and those around her, cancer might be curable today. PMID: 15504566

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.

~ScienceDaily

“Everybody knows Inflammation induces Cancer”, stated Francesco Marincola MD, Senior Investigator, NIH at the Host Defenses: From Bench to Bedside conference, Oct 6, 2006, UCSD. And not a single researcher in that room at UCSD disagreed with him.

The MP will keep your immune system strong so it can fight the cancer proliferation. Sure, I can't prove this, absolutely, definitely, right at this moment, but I have staked my future on the vision that in 10 years time there will be an entirely different treatment for your cancer diagnosis than you are now being given.

Never, ever, ever, underestimate the importance of dealing with the microbes causing the Th1 inflammation. It drives everything - including cancer proliferation.

I will state that, based on everything I have seen in the last several years, one definitely cannot 'cure' cancer without removing the causative Th1 pathogens.

Unless the pathology report indicates proliferation, the tumor is probably less dangerous than the underlying Th1 inflammation.

~Trevor Marshall, PhD

Although Th1 inflammation causes the cancer it is not possible to resolve that inflammation quickly. With the MP, it takes several years to get down the bacterial load to a point where the body's immune system is working properly again. It would need to be a quite benign cancer to not proliferate significantly in that time.

So reducing inflammation is a way to prevent, but we have zero data on whether inflammation reduction can be part of a cure. It may be, it may not be. As far as I know, there is no cancer therapy which is compatible with removing the bacterial load which is at the source of the problem.

It might be possible to partly reactivate the VDR during chemotherapy, with the agonist Benicar, and maybe one day we will try a study doing that. Since the VDR is responsible for transcribing a number of the genes which help deal the body with cancers, reactivating the VDR may be beneficial, I have no data…

The innate immune system is responsible for cleaning up cancer cells, but the bacteria disable the innate immune responseThe body's first line of defense against intracellular and other pathogens. According to the Marshall Pathogenesis the innate immune system becomes disabled as patients develop chronic disease., and it cannot be fully corrected in weeks, it takes years…

When you start reactiving the VDR with Benicar it will start to translate genes which have been shut off by the bacteria. One of these genes produces the protein “Metastasis Suppressing Protein.” It will certainly help your body to be producing that again. But will it be enough to affect the whole picture? It is impossible to predict.

I can tell you that in our cohort, which is made up of patients at very high risk of developing cancer, it is reported only very rarely, and then only in non-aggressive presentations.

~Trevor Marshall, PhD

Oct., 2008: While it is pretty certain that Benicar's reactivation of the VDR (and MTSS1) will likely reduce metastasis, that has little application once the cancerous cells have already started to spread. While the MP can probably stop metastasis from developing, once a tumor is in place, and growing, it is almost certainly too late to contemplate non-invasive therapies like the MP.

~Trevor Marshall, PhD

Question: Can the lab tell from the tissue whether my body was actively “cleaning up” the diseased tissue (cancer) while on the MP?

The lab doesn't look for “cleaning up” because it is assumed that cancer never gets better unless it is hit with a “nuclear bomb therapy” like chemo or radiation.

The key is always metastasis, and its presence or absence.

As I noted earlier, unless the Oncologist wants to aggressively search for metastasis, it is a pretty good bet that he is not too concerned about what he is describing as a 'tumor.'

~Trevor Marshall, PhD

June, 2008: The VDR transcribes the Metastasis Suppressor #1 (MTSS1) gene, which ends up as the “Missing In Metastasis” (MIM) protein. When the bugs are present this protein is missing. When Olmesartan gets the VDR working again, you can expect that protein to come back.

We have seen no metastasis in our cohort. Some old inactive tumors, yes, but no metastasizing agressive tumors as would normally be expected in a cohort as sick as ours.

~Trevor Marshall, PhD

June 27, 2008: For example, in 2006, D.L. Mager and team published a review article¹⁴ in the Journal of Translational Medicine called, “Bacteria and Cancer: Cause, or Cure?” According to Mager, “An overwhelming body of evidence has determined that relationships among certain bacteria and cancers exist.” In the paper, Mager details how research teams around the world have implicated Salmonella typhi in gallbladder cancer, Streptococcus bovis and E.coli in colon cancer, and Chlamydia pneumoniae in lung cancer. According to Mager, the mechanisms by which bacterial agents may induce carcinogenesis include “chronic infection, immune evasion, and immune suppression.”

~Bacteriality.com

Paris, Nov. 1, 2005: Study Links Bacteria, Lymphoma Around Eye

New research suggests that infection with bacteria from the Chlamydia family may play a role in the development of a type of lymphoma that affects the tissue around the eye, raising hopes that antibiotics may one day prove to be an alternative to chemotherapy or radiation.

~AP INTERNATIONAL

See also:

The role of bacterial pathogens in cancer ¹⁵

The role of viral and bacterial pathogens in gastrointestinal cancer ¹⁶

Bacteria and cancer: cause, coincidence or cure? A review ¹⁷

Wikipedia Cancer bacteria page

I am sure the damage is reversible, otherwise the bacterial load would not gradually reduce.

Many cancers grow on Th1 inflammation. One of the Th1 Chemokines is called CAM (cellular Adhesion molecule) and it is a key component both of how the plaque macrophages adhere to the arterial wall in atherosclerosis and also of how the initial cancerous cells stick to the tissue in cancer, and protect themselves from the immune system. More papers are coming out on both these things every month, but mainstream medicine has still to tie CAM to occult Th1 inflammation. It will take a decade for that to happen, IMO.

~Trevor Marshall, Phd
from Dr Marshall's Perspective: Host Defences - UCSD 2006

(323)462-6458

Dr Alan Cantwell, who, back in 1982, published photographs showing bacteria at the seat of Sarcoid-inflamed-tissue, is the author of a book called “The Cancer Microbe.”

When he published it he was made the laughing stock of many in the medical profession, who ridiculed the concept that Th1 bacteria are at the root of cancer. But he has now drawn a close group of colleagues around him, and we exchange info and ideas as each of the new studies comes out. And to me, as every week passes, it looks more and more likely that Alan was correct all along.

Knowing the pathogenesis is a long way from deriving a cure, but, IMO, we are close to defining the pathogenesis, and papers are being published from many groups who are working along similar lines. Patients (not MP patients) are reaching recovery after antibiotic therapy (not MP) in just a few cases, but cases that IMO, are significant.

I think Alan Cantwell is absolutely correct in saying that the CWD infection creates the environment and cytokines needed for cancer to start and proliferate. CAM apparently provides the adhesion necessary for the cancer cells to adhere to tissue, and to each other.

Since excess Vit D will shut down the cytokines, then it will be (and is being) shown as a cancer “cure” when it fact it is just delaying the inevitable. Another problem with study design - the studies just do not last for long enough to pick up the effects of chronic infection.

The next 20 years will see a lot of change in medicine, IMO.

~Trevor Marshall, PhD

Study raises hopes antibiotics may be an alternative

Some of Alan's papers are at http://JOIMR.org
You might also review Dr Broxmeyer's paper: Is Cancer Just an Incurable Infectious Disease? ¹⁸
and this one: Possible link to cancer evolution? ¹⁹

Alan's books are available from 'Aries Rising Press,' phone/FAX (323)462-6458
There are some secondhand copies of each at Amazon.com
The Cancer Microbe Four Women Against Cancer

An incredible book (by Alan Cantwell, MD).I just read it this weekend,and it is excellent.It's very hard to believe that this incredible research has been overlooked for so long.A quote from Florence Nightingale really sums up TH1 disease:“There are no specific diseases, only specific disease CONDITIONS.”

Especially fascinating was the section on the struggles between Antoine Beauchamp and Louis Pasteur. Pasteur hypothesized that all illness came from external germs, and this is what modern medicine is based on. Beauchamp, on the other hand, hypothesized that some illness came from inside of us, and not from external bacteria.This sounds an awful lot like Trevor's theory that TH1 illness is caused by a succession of illnesses, perhaps changing something inside of us, that makes us vulnerable to pleomorphic bacteria.

Fascinating reading, and I highly recommend it. If Dr Alan Cantwell reads this site, I gotta congratulate you. I'm looking forward to reading more of your books!

~Sam

Cantwell AR: The Russell Body - The Forgotten Clue to the Bacterial Cause of Cancer JOIMR 2003;1(6):1”

Summary: Recently, Elsevier, foremost publisher of world medical literature, peer-reviewed and published Lawrence Broxmeyer MD’s “Is cancer just an incurable infectious disease?” Medical Hypothesis 63 (986-996) 2004.

Here he discusses that publication:

Whitestone, New York, May 16, 2005: The word ‘cancer’ is of Latin derivation and means crab. By the turn of the 20th Century organized medicine had come to the conclusion that it was not a matter of whether infectious disease caused cancer, but which one. And in 1912, The Journal of the American Medical Association, (JAMA) in its editorial “Is Cancer of Infectious Nature?”, concluded that one investigator had “a very strong case in favor of his view of the infectious cause of cancer in general.” Just how was this mind set altered, and then totally submerged? It was an interesting subject, and so I decided to ask researcher Lawrence Broxmeyer MD more.

“For over two hundred years a cancer germ had been discovered and rediscovered, named and renamed, each scientist adding to the knowledge, but to no avail,” replied Lawrence Broxmeyer MD. “Then, in 1910, certain American medical powers did a 180-degree rotation, deciding that cancer was not caused by a microbe, and that anyone who thought otherwise was a heretic, a charlatan, or a quack. But Dr. Virginia Livingston MD and her superb network were none of the above, their meticulous peer-reviewed research and publications, done at the height of US post World War II technology. In her group were such world-renowned scientists as Dr. Florence Seibert and Dr. Eleanor Alexander-Jackson of Cornell. And Dean Burk, Head of Cell Chemistry at the National Cancer Institute (NCI) at that time, when asked, went so far as to say that Livingston’s cancer germ was as real and certain as anything known about cancer.”

~Is Cancer Just Another Infectious Disease?

Dec. 07: Dr Alan Cantwell's two presentations at our LAX 2006 conference are now available on YouTube at these URLs:

“The Cancer Microbe and the Russell Body” http://youtube.com/watch?v=sSst-APMmzA

“The Cancer Microbe in AIDS and Kaposi's Sarcoma” http://youtube.com/watch?v=TQm8Xi76AIw

Those of you who haven't yet had a chance to hear Alan talk about “The Cancer Microbe” will now be able to do so. The quality isn't as good as it is on our DVDs, but these are URLs that you can send to any of your friends who might be interested in trying to understand the links between the pleomorphic bacteria, Cancer and AIDS.

Alan also talks briefly about Lupus and Scleroderma.

Oct. 24, 2006: The Cancer Bacteria Forum

This interview was conducted by Ron Falcone on October 24, 2006
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.

Another interview: Bacteria and cancer: an interview with Dr. Alan Cantwell by Amy Proal

A list of Dr. Cantwell's published abstracts

Everybody knows Inflammation induces Cancer.

~Francesco Marincola MD, Senior Investigator, NIH

“Everybody knows inflammation causes cancer” and they can readily observe what low levels of cancers are found in the MP cohort. Getting rid of Th1 inflammation apparently is the silver bullet for prevention. Is there a silver bullet for cure? Probably not. At least, nobody has come up with a 100% cure just yet, and I suspect immunopathologyA temporary increase in disease symptoms experienced by Marshall Protocol patients that results from the release of cytokines and endotoxins as disease-causing bacteria are killed. will prevent them from doing so. (If any Professionals want a more detailed explanation of the putative pathogenic description please contact me directly).

~Trevor Marshall, PhD

Recent research is showing that some of the cytokines (caused by Th1 inflammation) are necessary for Cancers to take hold in the body. So it is most certainly incorrect to view Cancer as a totally separate disease from Th1 immune disease.

~Trevor Marshall, PhD

Elusive Bacterium – Russell Bodies ????? Cancer, Th1 inflammation basic cause????

I just finished off preparing for my presentation next week at Karolinska Institutet. I edited up a sequence of video I received from Andy Wright that I haven't shown in public yet, a sequence photographed of L-forms in blood of a Cancer/ ME /CFS patient.

What is amazing is the total destruction of the environment by the L-forms, the same shaped L-froms which are seen in lesser abundance on his other videos.

We do have a chicken-and-egg situation, however. Does the cancer weaken the immune system so that it cannot kill the intracellular forms, or do the intracellular forms so weaken the immune system that it cannot stop the cancer cell formation?

Of course, the L-forms are there in any case, so it does make sense to try and get rid of them. But what will be the outcome of doing this?

I will have a copy of the poster, with the video on it, showing at our own conference too. There will be some interesting discussions to be had there, I think:):)

PS: the video plays continuously on a tiny hand-held Pocket PC attached to the poster printout. :)

~Trevor Marshall, PhD

Omega-6 turns on inflammatory genes important in cancer

A cytokine-mediated link between innate immunity, inflammation, and cancer

Cancer, inflammation and the AT1 and AT2 receptors ²⁰

Here are some studies which make it appear that taking an angiotensin receptor blocker would not seem totally foreign or harmful to an oncologist:

Antiproliferative efficacy of angiotensin II receptor blockers in prostate cancer (cites one of Dr. Marshall's papers) ²¹

Angiotensin II, cell proliferation and angiogenesis regulator: biologic and therapeutic implications in cancer ²²

Functional expression of the angiotensin II type 1 receptor in human ovarian carcinoma cells… ²³

Pilot study of angiotensin II receptor blocker in advanced hormone-refractory prostate cancer ²⁴

Angiotensin II receptor blocker: possibility of antitumor agent for prostate cancer ²⁵

…the researchers fiddling with gene therapy really don't have it all together just yet. Until they figure out that the CWD pathogens are the things actually causing the mutations in the genes they are measuring, and that all the major diseases are all tied together by a common etiology, then they will be unable to understand what their data is actually telling them.

Dr. Trevor Marshall, PhD

Dec. 5, 2005: Tracking inflammation's role in promoting malignancy could lead to better treatments

Michael Karin is a professor of pharmacology at the University of California, San Diego School of Medicine and an American Cancer Society Research Professor. He is a cofounder of Signal Pharmaceuticals (now Celgene), and was elected this year to the National Academy of Sciences.

One problem with the current war on cancer is that much of it focuses on destroying the malignant cell itself while paying little attention to some of cancer's allies that are more prone to attack.

Cancer undoubtedly starts and ends with the malignant cell, and through tremendous efforts, we have identified many of the molecular and cellular attributes that define such cells. Genetic changes that lead to activation of oncogenes and/or inactivation of tumor suppressors result in aberrant control of cell proliferation and death, endowing the malignant cell with migratory and invasive properties. These changes, however, represent only the initial spark that ignites cancer's fire. Without fuel a fire cannot spread, and in cancer's case, inflammation feeds the blaze. Current cancer therapies that induce necrosis and inflammation may further fan the flames.

INSTIGATING NF-êB Two pathways lead to NF-êB activation. In the classical pathway, pro-inflammatory stimuli and genotoxic stress leads to IKKâ- and IKK-dependent phosphorylation of IêB, which results in proteasomal degradation and subsequent release of the NF-êB dimers. Activation of this pathway leads to increased transcription of genes in three functional classes, all of which contribute to tumor promotion and progression. The alternative pathway works independently of IKKâ and IKK. Click for larger version Click for larger version

A link between inflammation and cancer may have been suspected for millennia (see sidebar). Nevertheless, the connection has failed to catch on with most oncologists and has hardly been a mainstay of cancer research. Fortunately, however, this situation is quickly changing.

HINTS OF A LINK One of the problems in the inflammation-cancer field was the absence of well-defined molecular mechanisms linking chronic inflammation to tumor initiation and promotion. As is often the case, the solution came from another field. NF-êB, the transcription factor identified by David Baltimore and colleagues in 1986, has caught the attention of investigators interested in cell signaling and immunity. NF-êB is rapidly activated in response to numerous proinflammatory stimuli, as well as bacterial or viral infections. Once activated, it contributes to expression of many genes, whose products regulate immune and inflammatory responses.

Early connections between NF-êB and cancer were realized when its p65 subunit was identified as RelA, a relative of v-Rel, the oncogene of the reticuloendoblastosis virus. Thus, much of the early research sought out oncogenic mutations that would result in NF-êB's constitutive activation in malignant cells. A few such mutations were found, but were relatively rare and failed to explain the rather ubiquitous NF-êB activation in most types of cancer.1

My own interest in studying the NF-êB-cancer connection started with our observation, made simultaneously with the labs of Baltimore, Inder Verma, and Albert Baldwin, that NF-êB activation inhibits programmed cell death.2 Diminished apoptosis is an important contributor to malignancy, and infections and inflammation result in activation of NF-êB. So, the proposal that NF-êB provides a molecular link between inflammation and cancer was not too far-fetched.1

The challenge was to critically test this hypothesis in a convenient animal model. While it's impossible to completely inactivate NF-êB in the laboratory mouse, two general approaches allow its conditional inhibition in a given cell type. The first is based on conditional expression of a mutant form of a specific NF-êB inhibitor, IêBá, that is resistant to phosphorylation-induced degradation the so-called IêB super-repressor. IêB-SR expression retains NF-êB in the cytoplasm and selectively inhibits NF-êB-driven gene expression. The second approach is based on conditional inactivation of the IêB kinase (IKK) complex, responsible for signal-induced phosphorylation that leads to IêB degradation and NF-êB activation. Through inducible expression of IêB-SR in hepatocytes, Eli Pikarsky, Yinon Ben-Neriah, and colleagues tested the effect of NF-êB inhibition on the development of a type of liver cancer caused by chronic inflammation.

DOUBLE DUTY Inhibiting NF-êB in older animals already exhibiting chronic liver inflammation greatly retarded cancer development not because inflammation was prevented, but rather through the accelerated death of preneoplastic hepatocytes.3 We obtained similar results using cell type-specific deletion of the IKKâ gene in intestinal epithelial cells and a model of inflammation-associated colorectal cancer.4 Preventing NF-êB activation in intestinal epithelial cells dramatically inhibited tumor development, again by accelerating the death of preneoplastic cells.

We also examined the effect of selective interference with NF-êB activation in macrophages and neutrophils, two cell types that do not undergo malignant conversion in inflammation-associated cancers but are likely to contribute to their development. In this case we also observed inhibition of tumor development in epithelial cells but due to a different cause. Here, inhibiting NF-êB prevented production of cytokines and chemokines stimulate the growth of preneoplastic epithelial cells.

These studies not only established NF-êB's role in linking chronic inflammation to tumor development but also indicate two distinct mechanisms through which NF-êB promotes carcinogenesis. In the epithelial cell that had undergone malignant conversion, NF-êB inhibits apoptosis. At the same time, NF-êB in inflammatory cells provides early malignant epithelial cells with a variety of growth factors to accelerate tumor growth and progression.

The two types of experimental cancer described above belong to a group representing 15% to 20% of all cancers, in which underlying causes of chronic inflammation are easily detected. But what about the remaining cancers in which an underlying chronic inflammation or infection is not known to exist? Does inflammation play a causative role there as well?

To answer this question we used a model of chemically induced liver cancer in which no chronic inflammation is deliberately induced. Here, conditional deletion of IKKâ in either hepatocytes or inflammatory cells produced surprising results. Instead of reducing cancer load, selective NF-êB inactivation in hepatocytes greatly enhanced tumor development, but additional deletion of IKKâ in inflammatory cells resulted in a dramatic reduction in tumor number and size.5

We propose that in tissues such as the liver, excess cell death caused by inhibition of NF-êB and exposure to a cytotoxic carcinogen triggers compensatory cell proliferation. Nonetheless, the driving force is NF-êB in inflammatory cells, which provides surviving epithelial cells including cells that harbor potentially oncogenic mutations with growth factors. We propose that the release of cellular constituents during necrotic cell death drives this NF-êB activation.5

EXTINGUISHING THE BLAZE These studies, I believe, establish inflammation's role in providing and maintaining the fuel for many types of cancer, even those not associated with preexisting inflammation. And I think they bear relevance for cancer therapy as well. Most current anticancer drugs, as well as therapeutic radiation, kill tumors by inducing necrosis rather than pure apoptosis. And unlike apoptosis, necrosis results in activation and chemotactic attraction of additional inflammatory cells. This results in production of vast amounts of proinflammatory cytokines and chemokines that enhance the proliferation of surviving malignant cells. A single round of chemotherapy or radiotherapy is never 100% efficient, after all.

High levels of necrosis are commonly associated with rapidly growing tumors and are considered a sign of poor prognosis. Thus this cycle of necrosis, inflammation, and regeneration can be a major driving force in tumor development and progression. In the future, we need to find practical and selective ways to block this inflammatory response and combine anti-inflammatory drugs with preexisting chemotherapeutic and radiotherapeutic procedures. Thus, by attacking not only the malignant cell, but also inflammation, we should achieve much better survival rates than currently possible.

References

1. M Karin et al, “NF-êB in cancer: from innocent bystander to major culprit,” Nat Rev Cancer 2002, 2: 301-10. [PubMed Abstract][Publisher Full Text]

2. Z-G Liu “Dissection of TNF receptor 1 effector functions: JNK activation is not linked to apoptosis, while NF-êB activation prevents cell death,” Cell 1996, 87: 565-76. [PubMed Abstract] [Publisher Full Text]

3. E Pikarsky et al, “NF-êB functions as a tumour promoter in inflammation-associated cancer,” Nature 2004, 431: 461-6. [PubMed Abstract][Publisher Full Text]

4. FR Greten et al, “IKKâ links inflammation and tumorigenesis in a mouse model of colitis-associated cancer.” Cell 2004, 118: 285-96. [PubMed Abstract][Publisher Full Text]

5. S Maeda et al, “IKKâ couples hepatocyte death to cytokine-driven compensatory proliferation that promotes chemical hepatocarcinogenesis,” Cell 2005, 121: 977-90. [PubMed Abstract][Publisher Full Text]

~Michael Karin, The Scientist | Volume 19 | Issue 23 | Page 24

A cancer inflammation connection has long been suspected. Some have pegged its origins on Galen of ancient Greece. Modern connections were made in the 19th century by Rudolph Virchow.1 Yet this work was nearly forgotten until Harold Dvorak compared tumors to wounds that never heal.2 Later, Alberto Mantovani and colleagues implicated inflammatory chemokines in cancer growth and its spread through macrophage recruitment,3 whose role in cancer progression was demonstrated by Pollard.4

Fran Balkwill showed that the major pro-inflammatory cytokine tumor necrosis factor (TNF) may actually operate as a tumor promoter,5 and Ray Dubois and Mark Taketo demonstrated the importance of the pro-inflammatory enzyme cyclo-oxygenase-2 (COX2) and some of its products (the prostaglandins) in tumor progression and angiogenesis.6 Further, epidemiological studies demonstrate that chronic infections and inflammatory conditions such as hepatitis, gastritis, and chronic silicosis or asbestosis are major risk factors for cancer.7

Why, then, is so much effort focused on the malignant cell rather than the inflammatory cell?

References

1. F Balkwill, A Mantovani “Inflammation and cancer: back to Virchow?” Lancet 2001, 357: 539-45.

2. HF Dvorak “Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing,” N Engl J Med 1986, 315: 1650-9.

3. A Mantovani et al, “The origin and function of tumor-associated macrophages,” Immunol Today 1992, 13: 265-70.

4. JW Pollard “Tumour-educated macrophages promote tumour progression and metastasis,” Nat Rev Cancer 2004, 4: 71-8.

5. F Balkwill “Tumor necrosis factor or tumor promoting factor?” Cytokine Growth Factor Rev 2002, 13: 135-41.

6. RA Gupta, RN Dubois “Colorectal cancer prevention and treatment by inhibition of cyclooxygenase-2,” Nat Rev Cancer 2001, 1: 11-21.

7. H Kuper et al, “Infections as a major preventable cause of human cancer,” J Intern Med 2000, 248: 171-83.

Question: Why are studies showing that increased Vitamin D reduces the risk of cancer?

These studies are faulty, because the researchers did not understand the close relationship between inflammation and cancer. They draw inferences which are not supported by the data. That is why they use the word “may” so often. Most epidemiological studies on cancer and 1,25-DPrimary biologically active vitamin D hormone. Activates the vitamin D nuclear receptor. Produced by hydroxylation of 25-D. Also known as 1,25-dihydroxycholecalciferol, 1,25-hydroxyvitamin D and calcitirol. are flawed, for they fail to take into account the underlying biochemistry.

Th1 inflammation feeds the initial proliferative stage of Cancer. Without Th1 inflammation the cancer cells can't get adhesion to the 'healthy' cells and tissues, and can't become proliferative. Then, as the cancer starts to metastasize the inflamed stem cells are critical in enabling the spread of the inflammation, and the metastasis of the Cancer.

There are a number of groups in conventional-medicine who are coming to this understanding, although I am still only a small part of the only group to have comprehended that the Th1 inflammation is due to occult bacterial infection, and can be treated - (Alan Cantwell's group).

Vitamin D ingestion shuts down the ability of the immune system to to attack the Th1 microbes. I have a paper in the works which shows exactly how this happens, but I doubt that any journal would allow it to be published right now. The Vitamin D hype is so overwhelming, and the depth of ignorance about the VDR and how it controls the immune system is also overwhelming.

The epidemiological relationships between Cancers and Vitamin-D are short-term. Vitamin-D acts in a similar fashion to steroids, and reduces the incidence of cancers short-term, while enhancing the proliferation of the bacteria which will cause uncontrollable inflammation ten years, or so, down the line. Theoretical Biology allows one to understand this action, but the folks who are doing the Epidemiological studies have no interest in understanding the underlying processes. So they mis-interpret their data, and are funded by the manufacturing industry to continue doing so.

The early studies on Vitamin D and cancer were poorly done. More recent studies have shown that, if anything, the overall risk of cancer is raised in the presence of high levels of 25-D (risk raised above 80 nmol/ml or 32 ng/ml) http://www.msnbc.msn.com/id/21548773/

~Trevor Marshall, PhD

Dec. 28, 2005: Further research needed to provide definitive proof of the benefits of vitamin D

Our results demonstrate that calcitriol, alone or in combination with cytokines, modulates expression of MHC, CD11b, CD11c, CD14 and CD71 Ag on both monocytes and U937 cells, and impairs the phagocytic property of monocytes.

~Effects of 1,25-dihydroxyvitamin D3 and cytokines on the expression of MHC antigens, complement receptors and other antigens on human blood monocytes and U937 cells: role in cell differentiation, activation and phagocytosis ²⁶

~Professor Colin Cooper, of the Institute of Cancer Research, BBC News

I gave a presentation at Harvard last May, for DMM2007, which explained why animal models of immune disease and cancers do not work, because of the lack of homology between the animal VDR and the VDR of Homo sapiens: http://autoimmunityresearch.org/transcripts/dmm2007-harvard.pdf

Further, the behavior of Homo sapiens' VDR is different in healthy and Th1 diseased individuals, as the Th1 bacteria act to directly block the VDR's action. I gave a presentation on this at the Metagenomics Conference at UCSD last July: http://autoimmunityresearch.org/transcripts/metagenomics2007.pdf

So animal studies, such as the one you cite, can never come up with meaningful data in immune disease, data which translates directly to clinical practice, and indeed, they never have done.

Look, for example, at the TeGenero, study, which was even checked in primates (apes), prior to its disastrous introduction into the human environment: http://en.wikipedia.org/wiki/TGN1412

~Trevor Marshall, PhD

See also Extra Vitamin D does not reduce the risk of cancer.

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 Marshall

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 Marshall, PhD

Question: 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 ²⁷, 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 Marshall, PhD

Dec. 2007: 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 Marshall, PhD

WASHINGTON, Apr. 2007: Treatment may fuel cancer's spread, study finds

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.

Reference: Inhibition of TGF-beta with neutralizing antibodies prevents radiation-induced acceleration of metastatic cancer progression ²⁸

~Maggie Fox, Health and Science Editor,Reuters

This is a murine modelA model of disease which uses rats or mice to mimic human conditions., 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 Marshall, PhD

Apr. 16, 2007: Merck Predicts Big Fall In Cervical Lesions,But Data Are Complex

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 transmissionAn incident in which an infectious disease is transmitted. 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

~John Carreyrou, The Wall Street Journal

The following states have introduced legislation on making cervical-cancer vaccinations a school requirement:

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

~National Conference of State Legislatures, state legislatures

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.

~Trevor Marshall, PhD

NEW YORK, Oct. 10, 2005: Errors in cancer diagnosis common

In a review of patient specimens, errors in cancer diagnosis were seen in up to 11.8 percent of cases, according to a report in the medical journal Cancer. Moreover, in a substantial proportion of cases, the error caused some degree of harm for the patient.

The frequency and clinical impact of pathology errors in cancer diagnosis have not been well characterized, lead author Dr. Stephen S. Raab, from the University of Pittsburgh in Pennsylvania, and colleagues note.

In the present study, the authors evaluated diagnostic errors in patients who were seen at one of four hospitals in 2002 for a cancer work-up.

The frequency of errors varied between hospitals and ranged from 1.79 percent to 9.42 percent for gynecologics cases and from 4.87 percent to 11.8 percent for other cases, the researchers note. A significant link between the institution and the error cause was observed.

As for the cause of errors, up to 50 percent were due to misinterpretation with the remainder being due to poor tissue sampling.

The clinical impact of the error was significantly associated with the institution. On further analysis, it appeared that up to 45 percent of errors resulted in harm to the patient, ranging from further unnecessary diagnostic tests to loss of life or limb.

“It is exceedingly difficult to measure the true frequency of errors in cancer diagnosis because of the variety of detection methods used, bias, and the inability of institutions to secondarily review large case volumes,” the authors state.

“As part of a multi-institutional, national effort to improve practice, we are in the process of standardizing methods, decreasing bias by sharing cases and data among institutions, and establishing more accurate error frequencies by detecting errors using multiple methods,” they add.

SOURCE: Cancer, November 15, 2005.

~Reuters Health

One has to be awfully careful of cancer diagnoses when one has a Th1 disease.

The gold-standard Flow Cytometry test gives false positives, as it uses two markers BCL2 (bcl2) and CD10, which are both abnormal in Th1 disease.

It is critical that no cancer diagnosis be given unless the pathologist has stained for both Thymal masses (by using a T-cell stain) in addition to a B-cell stain. This is becoming more and more rare these days.

After all, once the oncologist gets to see you, he is unlikely to see Th1, if he/she thinks it looks a bit like cancer. Worse, many oncologists think that Chemo will 'fix' Th1 diseases like sarcoidosis. Of course, they couldn't be more wrong.

~Trevor Marshall, PhD

Flow Cytometry tests for cancerous tissue, which are the latest technology, use some markers (such as Bcl2) which are also present in sarcoidosis and other Th1 inflammatory conditions.

If you are going to let your oncologist operate, make sure that they use the older technique of MANUALLY STAINING for B or T cell proliferation in the tissue they biopsy. This will distinguish better whether the lymph nodes (or tissue from any suspicious area) are inflamed by Th1 inflammation or by a B-cell, possible cancerous, proliferation.

~Trevor Marshall, PhD

I had a somewhat similar problem in trying to arrange the staining to determine the relative proportion of T and B cells for my dad’s lung biopsy sample. The doctors did not know what I was talking about and they asked the pathology department who simply said, “we will do all the appropriate tests, don’t worry about it.”

So, what I did was ask the doctor if it was O.K. if I spoke to the pathologist and he said fine. The doctor had already agreed he would go along with what came of my discussion with the pathologist, when I told the doctor how important it was to me. I told the doctor, that based on research on sarcoidosis, that this test was important to help distinguish whether a mass was really cancer or actually sarcoidosis, according to a sarcoidosis expert that I had a great deal of faith in (Dr. Marshall).

So, I spoke to the pathologist and although it took a little discussion, and he may not have been wholly convinced of its necessity, he said that it was easy to do and if the doctor would order it, he could do it. So, then he talked to the doctor and they arranged for the proper order for the test. It is a fairly basic test, as I understand it, that has been around a long time. Hopefully, they will have enough of a sample from your biopsy still frozen so they can do it.

~Joyce Waterhouse

I wanted the DC4 and the T&B cells stained. They had to be sent out to do this. I spoke to Dr. Marshall and expressed my concern of the insurance not covering it. He told me not to worry about them if that was the case. His concern was to watch the rate of proliferation (growth rate) if their usual tests were positive. Therefore, I called and did not have them done.

~Lori

We caution sarcoidosis patients that Sarcoidosis can be misdiagnosed as cancer. Patients need to be their own advocate on this issue. This topic is covered in these threads: Cancer Diagnosis in Sarcoid Patients
Explanation of Biopsy (How to read a biopsy report)

There have recently been published reports of sarc misread as cancer in PET with F-18 fluorodeoxyglucose (FDG).

False-Positive Uptake of FDG in Hepatic Sarcoidosis ²⁹

Cancer and inflammation are tightly intwined and the physicians don't understand that yet. An oncologist always looks for/at cancer. All the PET is doing is looking at the radioactive decay when the glucose is metabolized in the tissue. Look at this animation for more detail of how the glucose gets broken down as its energy is released. http://www.johnkyrk.com/glycolysis.html

~Trevor Marshall, PhD

CA 125 is a glycoprotein expressed by a variety of tissues of mesothelial origin. It has classically been associated with ovarian carcinoma. It has also been reported to be elevated in certain granulomatous conditions. We describe a patient with sarcoidosis and an elevated serum CA 125 level and review the medical literature on this topic. Conclusions: Peritoneal sarcoidosis may “mimic” ovarian carcinoma in that it may present with peritoneal or abdominal findings and an elevated serum CA 125 level.

~Sarcoidosis Associated With an Elevated Serum CA 125 Level ³⁰

No one can measure many granulomas you had a few months ago to compare with how many you might have now. It's only upon autopsy that pathologists can get a small idea of the granuloma load.

As we've explained, lymph nodes enlarge due to infection, inflammation or cancer. You already have biopsy-verified sarcoidosis, which is the gold standard for diagnosing sarcoidosis. Try to understand that most physicians do not believe sarcoidosis can cause the damage it makes in reality. Most patients look pretty good and the internal damage is not visible. And most doctors have not dealt with sarcoidosis patients who are very ill.

Because of that, good, well-meaning doctors look for other explanations for sarcoidosis symptoms such as your inflammed lymph nodes. Add to that the fact that you have been losing weight (which is consistent with our experiences with the MP) and how litigious our society is in medical malpractice cases concerning missed cancer diagnoses, and you can see why your doctor is motivated to rule out cancer.

You alone can determine how much you are willing to expend time and energy to be poked, prodded and scanned to rule out cancers or any other differential diagnosis your physicians may suspect. But that testing can be expensive, time consuming and lead to nowhere. And you are the only one who knows how much of this you need before you are reassured.

Part of being an active member of your medical team sometimes means reassuring the doctor. Sarcoidosis is a scary disease for physicians, which is part of why they tend to get several specialists involved and do lots of testing. And they tend to want to do that whether the patient is stable or getting worse.

Sometimes a simple nap or brief rest can ease the discomfort of Herx. Our Tool List to check when Herxing is a great review to determine steps to take to keep Herxing manageable. If any of these work, it lends credibility to the concept that you are experiencing a Herx.

~Belinda

If either of these cancer tests gave a precise answer, a definite prognosis, and a clear treatment path for every possible outcome, then they would be very worthwhile indeed. You can find studies both supporting and denigrating every pathway. Medicine just doesn't have the answers yet, unfortunately.

~Trevor Marshall, PhD

You are correct to insist on every test which could provide support for the diagnosis. Cancer is a disease which is not well understood, and for which there is no certain cure (quality of life is poor in many patients who are declared 'cured' after Chemo). Every effort should be taken to ensure that the diagnosis is correct since chemotherapy will destroy the immune system and allow CWD bacteria to mulitply…then, when the chemo is discontinued, chronic inflammation exacerbates.

Cancer kills when it is “invasive.” It spreads from the primary site to other sites, and proliferates there. The only sure way to know the disease is cancer is to allow it to progress to a point where there is no question you have a proliferative disease. This is not usually an approach taken by 'modern medicine' but I mention it because it does contrast the risks of misdiagnosis and early intervention with those of late diagnosis and inability to intervene.

The two considerations have to be balanced, and I personally don't believe today's oncologists fully understand that balance. I also believe that they have been overtaken by the epidemic in Th1 immune disease, and therefore do not understand how it factors into the liklihood of misdiagnosis.

Ultimately, the immune system and Cancers are very closely related. There is a paper talking about the complexity of this relationship which I was reviewing last night http://www.tbiomed.com/content/3/1/6

We will be discussing the links between Cancers, AIDS and th1 Immune disease at our LAX conference.” (See the 2006 LAX DVDs)

~Trevor Marshall, PhD

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

BCG is live bacterium, Mycobacterium bovis. It is fingered as having directly caused Sarcoidosis, for example:
Juvenile sarcoidosis after BCG vaccination ³¹
Sarcoidosis following B.C.G. vaccination in a lymphopaenic boy ³²

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:
A randomized trial of intravesical doxorubicin and immunotherapy with bacille Calmette-Guérin for transitional-cell carcinoma of the bladder ³³

The author recently backed off from his 1992 blanket recommendations:
Bladder cancer: current optimal intravesical treatment ³⁴

Here is what the CDC has to say about its use in prophylaxisis against TB

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 infectionAn infectious cascade of pathogens in which initial infectious agents slow the immune response and make it easier for subsequent infections to proliferate.' 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 Marshall, PhD

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 agonistA substance such as olmesartan (Benicar) or 1,25-D which activates the Vitamin D Receptor and transcribes the genes necessary for a proper innate immune response., like the drug described here:
Human Bladder as a Novel Target for Vitamin D Receptor Ligands ³⁵

This paper contains more information about BPH:
Inhibition of prostate growth and inflammation by the vitamin D receptor agonist BXL-628 (elocalcitol) ³⁶

See also Interview with Gene Johnson

Bladder tumors

-I understand your emotions re bladder cancer. I went through it but can now say I am convinced the MP has strengthened my immune system to prevent it again. My last two bladder scopes after surgery to remove tumors were negative (for the past year) and the FISH chromosomal test of the bladder wash was also negative for cancer. Take a look at my MP thread under “edj2001”, I just posted an update earlier today. SEE Gene in phase 3 My doc called Dr. Marshall and he explained to doc why BCG was not an option. I also declined chemo due to the disruption to the immune system. As Dr. Marshall said in a post the VDR transcribes an anti metastasizing gene along with others to control/prevent cancer.~edj2001

Question: I recently came across an article while doing a medline search entitled, “Association between low levels of 1,25 dihydroxyvitamin D and breast cancer risk.” The conclusions of the study were: “These data are consistent with a protective effect of 1,25-D for breast cancer in white women.” This concerns me because I carry the brca-1 mutation and so am already at a very high risk of getting breast cancer and according to the study lowering my 1,25-D will only further increase my risk.

The brca1 gene has only been shown to be a MARKER of breast cancer, not a cause. Second, Th1 inflammation is almost certainly a necessary precursor to breast cancer (i.e. a cause) Mutations in brca1 and brca2 are associated with increased incidence of cancers, not necessarily causal.

I have just come from a “Diseases of (DNA) Transcription” conference at the Salk Institute where there was not one scientist who knew exactly how genes mutate, or why, or what it means.

Sure, there are statistics linking shifts in haplotypes with certain diseases, but they are just as likely due to the mix of persistent pathogens your family has been passing down, as they are due to any Mendelian variation of the gene pool.

A person has to assess the relative likelihood of dying from Th1 disease and dying from cancer. 1,25-D is a measure of the Th1 reaction and is therefore intimately associated with breast cancer, in ways that this study investigators never dreamed of. If one doesn't understand the subtleties behind this kind of research, then one is going to have trouble assessing relative risks in medicine.

I have seen a number of Th1 patients erroneously diagnosed with cancer. The diagnosis of cancer is not precise. Flow cytometry senses the presence of both CD10 and bcl2, and these are elevated in Th1 disease. False positives are a fact of life, but patients rarely find out about them. False positives increase the apparent 'success rate' of oncology, and there is therefore little incentive to minimize them.

Please listen to my discussion of these genetics, including the bcl2 issue, on the DVDs of my talk on Familial Aggregation at the conference.

BRCA genes are turning out essentially useless to tell Breast Cancer predisposition, as now they are falling back on the old epidemiological factors before even screening

The relationship between cancer and inflammation is controversial. (IMO) A good review of the issues is available from JOIMR

Additionally, two of the markers used in Flow Cytometry (used as the 'gold standard' for breast cancer) bcl2 and CD10, are both elevated in the inflammatory diseases, leading to misdiagnosis in a lot of cases, probably in a majority of cases. These misdiagnoses also bias the epidemiological studies.

The BRCA1 and BRCA2 genes are probably not good differential markers of cancer vs inflammation. The pathology report from MD Anderson again states there is no sign of proliferation of the cancer into the surrounding tissues, so the sentinel node biopsy is probably the best way to determine whether the lump is an old cancer or is still active.

Less than 10% of Breast cancers are due to BRCA1, most are due to Estrogen up-regulation. Since the Estrogen receptor transcribes the protein which folds to form the Vitamin D Receptor, excessive estrogen is probably associated with a disabled VDR, IMO.

~Trevor Marshall, PhD

CHICAGO, Jan. 8,2008: BRCA genes get help in causing breast cancer-study

The risk of breast cancer among women carrying the well-known BRCA mutations is also affected by other genes, researchers said on Tuesday.

The study of close relatives of breast cancer patients who had one of the BRCA mutations showed the risk of the disease varied greatly between families, indicating that other genes must be involved.

So a woman who knows she has a BRCA1 or BRCA2 mutation still cannot know precisely what her risk of breast cancer is, the researchers reported in the Journal of the American Medical Association. “The implications of that are that there must be other genetic factors involved here,” Dr. Colin Begg of Memorial Sloan-Kettering Cancer Center in New York, who led the study, said in a telephone interview.

“Because if some carrier families have higher risks than other carrier families presumably there are other genes being passed through these families that elevate or lower the risks,” Begg said.

Begg's team studied 2,000 women diagnosed with breast cancer, and the families of the 181 patients who had BRCA mutations. They found that 5 percent of those with cancer in one breast had a BRCA1 or BRCA2 mutation and 15 percent of those with cancer in both breasts did.

All had been diagnosed early, before the age of 55. But only 25 percent of all the patients had a close relative with breast cancer. And 58 percent of those with BRCA1 or BRCA2 mutations had a mother, sister or other close relative with the disease, the researchers said.

They said this means a close relative of a BRCA carrier with breast cancer has a 40 percent risk of developing the disease herself by age 70. But this is an average risk and they found a considerable amount of variation in risk from one family to another.

Search for more genes

Among carriers, their risk of developing breast cancer by age 70 has been estimated at anywhere between 50 percent and 85 percent, Begg said.

They looked to see if perhaps the type of BRCA mutation might affect risk, but it did not appear to. Many different types of mutations were found but they usually did not significantly affect whether a woman or her relatives had breast cancer, Begg's team said.

“There's a lot of research going on at the moment in general to find additional breast cancer genes. What we're saying here is that research is likely to be successful,” Begg said.

~Andrew Stern, Reuters

The BRCA1 and BRCA2 mutations are most common among Jews of Ashken— descent. At least 2 percent of these descendants of Eastern European Jews are carriers. The incidence is lower in the general population, but not enough testing has been done to put a firm estimate on it. About 465,000 women died of breast cancer last year, making it the leading cause of cancer death among women worldwide, according to the World Health Organization.

Many new papers linking Vitamin D / VDR to breast cancer. Here are some that Doc might be interested in looking at:

Identification of novel mediators of Vitamin D signaling and 1,25(OH)2D3 resistance in mammary cells ³⁷

Overexpression of ER and VDR is not sufficient to make ER-negative MDA-MB231 breast cancer cells responsive to 1alpha-hydroxyvitamin D5 ³⁸

Vitamin D and cancer ³⁹

See also:

Vitamin D and cancer

Here is some specific information to help you understand the complexities of making absolute causal inferences from genomic data, such as many oncologists have done with respect to the association between brca mutations and familial incidence of cancers. You will find a summary of the the Staph aureus genome at this URL.

Search for the following annotation: “Pfam match to entry PF00533 BRCT, BRCA1 C Terminus (BRCT) domain, score 54.4, E-value 2.7e-13”

This means that there are similarities between the way the BRCT gene at the C Terminus of homo sapiens BRCA1, and the way this gene in the Staph aureus bacterium behave.

Please note that I am not concluding that this apparent homology is proof of anything, except that we still have so much to learn about the human body, and the way it works, and the pathogens with which it co-habits this planet.

The more I learn the less I realize I really know. I just wish physicians were trained to recognize the same phenomenon :)

~Trevor Marshall, PhD

A painstaking scan of the DNA of tumor cells shows hundreds of previously unsuspected genes are involved in cancer, researchers said on Wednesday .. They found more than 1,000 different mutations in just one family of genes taken from 200 samples of breast, stomach, colorectal and other common tumors.

~http://www.alertnet.org/thenews/newsdesk/N07459256.htm|Alertnet.org]]

“However, Mawer, et al, reported that 1,25-D is such a sensitive indicator of the Th1 immune response that it can even be used to determine prognosis in breast cancer [23}. As the level of 1,25-D falls, the level of the body’s ability to mount a Th1 response is also falling, and the prognosis becomes less favorable.”
Serum 1,25-dihydroxyvitamin D may be related inversely to disease activity in breast cancer patients with bone metastases ⁴⁰

This seems to indicate that it might be possible to use the level of 1,25-D as one means of suggesting whether or not breast cancer treatment is effective if doctors know how to interpet the results. But you'll note that the patients in the above study had bone metastasis.

Nobody knows the cause of cancer. But those who are close to a pathogenesis are publishing that the Th1 inflammatory cytokines, especially the chemokine CAM, are key to the cancer getting a hold in the body.

How does this relate to reduced or increased risk from Vit D deprivation? Nobody knows for sure, although it is obviously a pretty good idea to get rid of any Th1 inflammation.

You might also ask Doc how he/she assesses the relative risk factors. There has been a reluctance for clinical medicine to recognize that Vitamin D is not really a vitamin, but is an immune modulator (at least in its active steroidal 1,25-D form). As far as I know, very few cancer researchers have been looking into the biochemistry of Vit D and cancer, although some have. You will find some references to those studies in our paper Sarcoidosis Succumbs to Antibiotics – Implications for Autoimmune Disease

Our Russian paper cited some of this work as well. There is beginning to be more research done in this area, but it is still early-days.

~Trevor Marshall, PhD

The key statement is that the growth is “progressive.” IMO this is the gold standard. How fast is the lump growing, and does it need immediate intervention. IMO such an evaluation cannot be made with anything other than a series of MRI or CT images, at intervals, with clear signs of progressive growth.

If the growth is not fast, and if Doc is not sure that the mass is B-cells, then there is also no pressing need for intervention (IMO).

Sarcoid granuloma, Th1 cysts and Thymal masses take months to enlarge, and not weeks.

I respectfully disagree with your doctor, it is VERY important to stain the histology of a patient with inflammatory disease in order to differentiate T cells from B cells, and Thymal masses from malignant tumors.

~Trevor Marshall, PhD

See Diagnosing cancer accurately

Q: “I have microcalcifications, instead of a lump, which is why a stereostatic biopsy with ultrasound is being done.”

Re “microcalcifications” see A Review - Vitamin D and Calcium in Sarcoidosis (7-5-03)

It says in part:

At levels above about 42 pg/ml, the 1,25-D (generated by the sarcoid inflammation) begins to stimulate bone osteoclasts http://edrv.endojournals.org/cgi/content/full/21/2/115, causing bone to be resorbed (dissolved) back into the bloodstream. Not only does this lead to osteoporosis, but also to calcium being deposited into soft tissue of the body, including the lungs, breasts, and the kidneys (where it forms kidney stones).

A case of granulomatous mastitis mimicking breast cancer ⁴¹

Idiopathic granulomatous mastitis: time to avoid unnecessary mastectomies ⁴²

Idiopathic granulomatous mastitis: case report and review of the literature ⁴³

Idiopathic granulomatous mastitis (with necrosis). Report of a case diagnosed with fine needle aspiration cytology ⁴⁴

Granulomatous mastitis (with necrosis): a clinicopathological review of 26 cases ⁴⁵

“Microcalcifications” are a hallmark of Th1, and I am puzzled why they are now regarded as a sign of 'cancer'. Still, given the lack of knowledge generally being exhibited by Oncologists these days (my 'exhibit 1' is this paper from Reuters earlier today Vitamin D may help slow breast cancer).

The key thing to remember is that cancer kills because it is progressive. The cells grow too fast for your immune system to deal with. Since you are now in Phase 3, your immune system should be capable of doing a pretty good job of cleaning up any cancer cells which happen to form. So I would not be too eager to intervene until I knew that I really had a proliferative disease.

Finally, here is a quote for Doc - “Everybody knows Inflammation induces Cancer”- Francesco Marincola MD, Senior Investigator, NIH (spoken during his presentation at the “Host Defences” conference at UCSD last week).

I would be happy to chat with your oncologist about the problems with the flow cytometry markers, if that would help. to make sure they are not relying on flow cytometry markers.

At the very least, you need to have the biopsy tissue stained to differentiate B-cells and T-cells. You also need to get a better assessment of what the rate of proliferation might be.

Be sure to get an “open” biopsy or an “excised” biopsy (not a needle biopsy).

-If necessary have someone to support you as a patient advocate to understand and assist you in achieving your best interest. -Prepare in advance by asking on the Board about your situation. -Discuss your needs with your Dr before the surgery. -Ask the Dr to confer with Dr Marshall.

There is little doubt amongst some of my professional colleagues that many cancers are rooted in Th1 inflammation. See, for example, Dr Alan Cantwell's papers at http://www.joimr.org

It is dangerous to assume that the MP in any way harms the prognosis of a cancer. There is no data indicating that this would be so, and there is one case history indicating that it doesn't.

~Trevor Marshall, PhD

This article published in 2003 in the journal of the American Family Physician explains that “CA 27.29 also can be found in patients with benign disorders of the breast, liver, and kidney, and in patients with ovarian cysts.”⁴⁶

Sarcoidosis would be considered a benign (non-malignant) disorder that can affect the breast, liver, kidney or ovary.

The CA 27.29 test is not reliable in all cases. Information from the FDA says, “Because the (CA 27.29) test did not detect the cancer antigen in all cases and detected it falsely in others, FDA based its approval on use of the test in conjunction with other procedures to monitor the recurrence of Stage II or Stage III breast cancer.

This puts me in a difficult position. I am not an oncologist, I am a scientist. I am interested in the pathogenesis of cancer. I am far less interested in the tests which are currently thought to be indicative of cancers, as these tests change from year-to-year.

If this was a report on, for example, my wife, I would want her to discuss the following with Doc.

1. A needle biopsy is usually not capable of preserving the granulomatous structure characteristic of Sarcoidosis. The diameter of the needle is small, and granuloma are often large by comparison. This makes microscopic histological examination somewhat uncertain without specific staining.
2. I see no attempt to stain for T cells or B cells.
3. The issue is not that a 'mass' was found - I would ask if it is a Thymal mass (indicating T-cell immune disease) or a proliferative mass (B-cell cancer)
4. The marker “c-erbB-2” which is supposed to indicate a bad prognosis for Breast Cancer is reported as negative.
5. Only one out of the three markers was positive, and that marker seems to be a pretty general marker to me (an Estrogen Receptor Protein)

I would want to at least ask Doc to wait for the remaining test results to come back before I had to see a surgeon. I know what the surgeon's specialty is, and I know what he is going to want to discuss.

Again, I am not trying to give you advice, but only guidance as to what a scientist sees in the data you posted. Only your Doc and Surgeon can help you decide what course to follow. Only they are licensed to look after your health. I would be happy to discuss the T-cell vs B-cell issue with Doc, if that would help.

~Trevor Marshall, PhD

Mammography is a procedure using x-rays to create images of breast tissue. It is used to detect and evaluate abnormalities such as tumors and cysts. There are two basic forms of mammography: screening and diagnostic.

Even the best radiologists are will inaccurately read a mammogram in 2 to 3 percent of cases, while some series show that other doctors incorrectly read the images in 20 percent or more.

~Jerome Groopman, MD, Chapter 8: The Eye of the Beholder, How Doctors Think

A screening mammogram is used to evaluate for cancer in women with no symptoms and no history of breast surgery. Mammograms are used for comparative study: to compare the left breast to the right, and to compare current films to older films. The goal of regular screening is to detect small cancers (when they are still small) because they are easier to treat and usually have a better prognosis for the patient. It is suggested women have a mammogram around age 35 to provide a baseline study for comparison with mammograms taken when they are 40 and older.

How often women younger than age 50 should have a screening mammogram is controversial. Most agree that women between 50-69 may significantly reduce their risk of dying from breast cancer by having a mammogram every 1-2 years, but there is insufficient evidence supporting the same benefit for women between age 40-49.

The National Cancer Institute and the American Cancer Society recommend that women 40 and older have a mammogram every 1-2 years, and that women with significant risk factors should discuss earlier screening, and how often, with their own physicians.

In standard mammogram studies, one breast is positioned between two panels and slowly compressed. Two images of each breast are obtained: a side view (from the center of body to the side) and a view from above. X-rays penetrate the breast tissue to produce images recorded on film. Different tissues in the breast absorb x-rays differently, resulting in shades of black, gray, and white on the film:

Fatty tissue absorbs little of the x-rays to appear black or dark gray.

Normal fibrous and glandular tissues (such as milk glands, lymph nodes) contain fluid, which causes them to absorb a moderate amount of x-rays and appear light gray.

Fibrous and glandular tissues may contain calcium and appear nearly white or completely white.

Cancerous tissues contain fluid and sometimes calcium, which makes small cancers difficult to distinguish from normal breast tissue. As a cancer grows, it begins to appear whiter than breast tissue on film.

Comparison with prior mammograms helps identify changes in patterns on the film that may identify small breast cancers. Findings from screening mammograms Because small cancers are difficult to distinguish from normal breast tissue on a mammogram and may not be palpable during a breast exam, some will be undetected. Cases that escape diagnosis are referred to as false negatives. These cancers are usually found after they have grown to a size that can be seen or felt.

Other conditions in the breasts may look similar to cancer, such as calcifications, fibrosis or cysts. The radiologist will order additional studies focusing on the area of the breast with any suspicious lesion. If additional studies are inconclusive, a biopsy may be recommended. If the biopsy eventually proves to be non-cancerous, the finding is called a false positive.

Calcifications often develop in women's breasts because breasts produce milk, which contains calcium. Because many breast cancers contain calcifications, the doctor will want to determine whether any calcification is in cancerous tissue. Most calcifications can be evaluated using additional mammogram views. Some that are difficult will require additional studies.

A mass, or a lump, found on a mammogram may be a lymph node, cyst, or fibroadenoma (fibrous milk gland). These types of masses usually are easy to identify and do not require additional studies. A new mass or a mass that has changed or grown since the last mammogram will usually be evaluated using ultrasound. A mass may be due to an inflammatory disease such as sarcoidosis. Sarcoidosis should be considered in the differential diagnosis of a mass in any patient with a previously suspected or confirmed diagnosis of sarcoidosis.

Several masses can be seen in women who have fibrocystic disease. If there is a change in the size or shape of the edges of a mass, or if a suspicious calcification is seen within a mass, the radiologist may order additional studies.

An area in one breast that has a distinctly different appearance than the same area in the other breast is referred to as asymmetric density. This finding usually requires additional studies using mammography and/or ultrasound.

Dense breast tissue can make mammogram evaluation difficult because the tissue can obscure small cancers. Pre-menopausal women usually have denser breast tissue than women who are past menopause.

Diagnostic imaging is required under these conditions:

• Breast implants

• Severe fibrocystic disease

• After surgery for early breast cancer that did not remove the entire breast

• Abnormal findings on a screening mammogram (change in a mass)

• New findings during a clinical breast exam (lump, nipple discharge)

Types of imaging used for diagnosis include special mammography views, views from different angles and ultrasound. If the findings obtained from additional studies indicate that there is a solid lesion, a biopsy will be recommended.

Magnification produces larger imaging of a portion of the breast that contains calcifications or masses.

Spot compression applies more pressure to a small region in the breast. This thins out an area of dense tissue so the x-rays produce a clearer image, making it easier for the radiologist to see if the tissue is normal or abnormal. This is useful in women with denser breast tissue, where it is difficult to get adequate compression for best imaging.

Sometimes views of the breast from different angles are required to see a questionable area. Typical additional views include:

• Cleavage view - Both breasts are compressed between a set of panels at the same time and a top-to-bottom view of a suspicious finding in tissue between the breasts.

• Rolled view - The breast is rolled to the right or left, compressed, and a top-to-bottom view is taken of a questionable area located in dense tissue.

• Mediolateral view - The view is taken from the center of the chest to the outer side of the breast.

• Lateromedial view - The view is taken from the outer side of the breast to the center of the chest.

Ultrasound is used to help determine if a mass is a cyst or a possible cancer. Ultrasound is performed with a small, handheld device called a transducer. First, a gel is spread on the skin. Then the technician passes the transducer over the breast, which directs sound waves through the skin into the body. The sound waves create an image of the breast on a computer monitor

Recent research (June 2007 published in August) indicates that an MRI which doesn't give off radiation detects 97% of breast tumors, but is known to give false positives. Researchers also indicated that needle biopsies can be guaged better by MRI's, but it is essential one gets the procedure done by one of only a handful of experienced rad doc in the US. Mammograms detect around 51% of tumors depending on whose research one reads. Specifically they are better for detecting microcalcifications to test for DCIS stage 0 than tumors.

MRIs do not hurt, nor do the Ultrasounds which is one of the reasons I refused (and will continue, ) to have mammograms and they don't give off radiation. Had the rad doc told me she was looking for microcalcifications, I would not have had the mammogram at all. I guess it was my mistake for not pushing the issue. The place I now go for treatment is at a major cancer center of a top medical school. We'll see how the next MRI goes in January. If something questionable shows up, then I will PM you for further info on Thermal Imaging.

~DNStog

I did some research into thermal imaging (breast thermography) as an alternative and ended up calling Dr. George E. Chapman, who has written a number of texts on using thermal imaging and interpreting the results of thermal imaging, especially for early detection of breast cancer to learn more about it. (He did say that a baseline mammogram is important for interpreting any future results showing changes large enough to register on a mammogram.)

If I can remember this right, he said that the heat generated by the extra blood flow to a tumor will show up on a thermal image photo (they use special heat sensing cameras) up to ten years before the tumor would be large enough to be detected by a mammogram. Of course, heat caused by other reasons (such as infection) would show up as well, so having a qualified person, such as Dr. Chapman, interpret the results is as important as the training of the technician who takes the images.

My images showed some areas of black (cold temperatures) that were interpreted as stastically being most frequently associated with cystic and fibrocystic breasts (suggestive of hormone imbalance).

Here is part of the report: “performed 20 minutes post onset of examination and following a 60 second hand soak in 50 degree water. This provides an autonomic challenge and a response of sympathetic vaso-constriction. The skins microcirculation is further shut down and we are able to contrast any non-responsive blood vessels that may be associated with malignant neoplasms. This includes the neo-angiogenic blood vessels and those that are dilated because of nitric oxide.”

At the time I was also having abdominal pain and paid for an additional set of images of the abdomen. The report stated: “Increased heat is observed above the umbilicus and prmarily at the right upper abdominal quadrant. Question pancreatitis and/or gall bladder dysfunction based on thermal patterns. May be associated with 'Head Zones'. Additional clinical information is needed for confirmation.”

Kind of interesting, but I would not pay for it out of pocket unless I felt it would provide more clarity on an important health issue. Perhaps such a procedure is available in your area. I was told that Kaiser in Northern California is using it as a standard diagnostic tool now. I am sure it was much kinder and gentler than what you describe above.

I also remember him making a comment about the equipment for mammograms being 1970's (?need to check this date?) technology, approved for use at around the same time as the thermal imaging technology. But while the mammogram equipment is basically the same to this day, the equipment for thermography has moved forward significantly with computer analysis, etc.

~Joyful

See Chemotherapy and Radiation

Where did you get the idea that chemotherapy was in any way compatible with healing from your Th1 disease? Chemotherapy is immunosuppressive, aggressively so, and chemo will allow your bacterial load to return, by shutting down your immune system.

My assessment of your situation is that the MP has restored your immune system, allowed it to fight the cancer, which was an aggressive ductal carcinoma, but has (reportedly) been inactived by your immune system. You have dodged the bullet that killed your forebears. I know how tough it is to tread the line between old-school and new-school medical knowledge, but that is what your oncologists are forcing you to do.

Take another hard look at Alan Cantwell's presentations at the LAX conference. You are being given a choice, and those who are putting pressure on you to begin chemotherapy do not seem to have any concept of where you have been, or where you are capable of going.

~Trevor Marshall, PhD

NEW YORK, Nov. 22, 2007: Transition from polyp to cancer age-dependent

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.

~Reuters Health

Nov. 5, 2007: Folic Acid Linked To Increased Cancer Rate, Historical Review Suggests

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.

~ScienceDaily

A colonoscopy may be warranted if you are at high risk and is not contraindicated on the MP. It's okay to continue MP meds but you may want to adjust them to reduce immunopathology so you are feeling your best during this time.

If either of these cancer tests (PSA) gave a precise answer, a definite prognosis, and a clear treatment path for every possible outcome, then they would be very worthwhile indeed. You can find studies both supporting and denigrating every pathway. Medicine just doesn't have the answers yet, unfortunately.

Trevor Marshall, PhD

Oct. 4, 2006: Antibiotic Fights Chlamydia-Linked Eye Cancer

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.

~HealthDay News

Pleomorphic Bacteria as a Cause of Hodgkin's Disease (Hodgkin's lymphoma): A Review of the Literature by Dr. Alan Cantwell, M.D.

Anti-Inflammatory Drug Prevents Liver Cancer in at-Risk Liver Patients

If you print out a copy of this Reuters news service article Positive CT scan for lung cancer may resolve and give it to Doc, you might find that he is prepared to continue your husband on antibiotics. (You might also print out the actual abstract).

The article is fascinating in that it again points out that the only certain way to know if cancer is present is to allow the passage of time, so that the cellular proliferation can become obvious. Unfortunately, because cancer therapies are ineffective unless started early, few oncologists have been allowing patients to “make sure” that their CT shadows were really cancer before pushing them into chemotherapy. This study shows that a large proportion of Lung cancers might be misdiagnosed.

The researchers note that possible cancer diagnosis in 12 of 41 patients had fully or partially resolved when therapy was delayed 2 months. In another group, 29 of 39 had full or partial resolution.

While this alone ought to be a bombshell, what is intriguing is their concluding statement:

“we recommend a course of antibiotics followed by another CT within 2 months to people with patchy consolidation or nonsolid opacities detected on the baseline screening and all those with new nodules on repeat screening. It must be emphasized that the use of antibiotics and short-term CT follow-up is only one of the options in the regimen of CT screening for lung cancer,” the researchers add, “and further research in this area promises to continue to improve the efficiency of CT screening for lung cancer.”

These researchers are prepared to prescribe antibiotics, just in case, and it is possible your Doc may do so, too. But I would ask Doc for Minocyline, rather than Doxycycline, as Mino is more effective against one of the nasty plasmid-bearing species, Staph. In any case, Doc might well be more familiar with Mino, since he/she is probably prescribing Mino to his/her Acne patients:)

~Trevor Marshall, PhD
from A visit with Dr Alan Cantwell

Having spent 50 years of my life desperately trying to escape from secondhand smoke, I feel strange having to say that I am not nearly so sure that the diseases attributed to smoking are indeed caused by smoking. There are too many “wide-brush” statements about “XXX lives lost to smoking” yet the people making them have no idea of the underlying disease process by which smoking is supposed to cause death.

It isn't cancer, as it is now pretty clear that cancer rises from Th1 inflammation and an incompetent immune system (for example, review this paper - especially the observation about Kaposi's sarcoma).

Nobody has come up with a molecular rationale for how smoking causes cancer. Maybe they are all making the same mistake of over-reaching which we see in the Vitamin D research:)

In no way am I saying that smoking is not bad for the immune system, and for the body as a whole, am just not convinced it is quite as bad as most folks would have us believe. We need to make sure we focus our energies on the cause of disease, for it is the cause which we have to defeat.

~Trevor Marshall, PhD

A lot of researchers say that nicotine is not carcinogenic….

Apoptosis. 2007 Nov;12(11):1927-43.Related Articles, Links

Nicotine and apoptosis.

Zeidler R, Albermann K, Lang S.

ENT-Department, University of Munich, c/o GSF-Forschungszentrum, Marchioninistr. 25, 81377 Munich, Germany. zeidler@gsf.de

Cigarette smoking is associated with a plethora of different diseases. Nicotine is the addictive component of cigarette but also acts onto cells of the non-neuronal system, including immune effector cells. Although nicotine itself is usually not referred to as a carcinogen, there is ongoing debate whether nicotine functions as a 'tumor enhancer.' By binding to nicotinic acetylcholine receptors, nicotine deregulates essential biological processes like angiogenesis, apoptosis, and cell-mediated immunity. Apoptosis plays critical roles in a wide variety of physiologic processes during fetal development and in adult tissue and is also a fundamental aspect of the biology of malignant diseases. This review provides an overlook how nicotine influences apoptotic processes and is thus directly involved in the etiology of pathological conditions like cancer and obstructive diseases.

Publication Types: Review

PMID: 17846896

Cancer Cell. 2003 Sep;4(3):159-60. Links Comment on: Cancer Cell. 2003 Sep;4(3):191-6. Environmental tobacco smoke, carcinogenesis, and angiogenesis: a double whammy?

Gazdar AF. Hamon Center for Therapeutic Oncology Research and Department of Pathology, UT Southwestern Medical Center, Dallas, TX 75390, USA. adi.gazdar@utsouthwestern.edu In this issue of Cancer Cell, Zhu and coworkers demonstrate that environmental tobacco smoke (ETS) results in tumor angiogenesis, and provide evidence that the responsible factor in ETS is nicotine. While a weak carcinogen, nicotine promotes carcinogenesis by a number of different mechanisms. The authors' findings provide further evidence of the harmful effects of ETS and indicate the desirability of reducing exposure to it. PMID: 14522247

Toxicol Sci. 2004 May;79(1):1-3. Links Comment on: Toxicol Sci. 2004 May;79(1):75-81. Nicotine: potentially a multifunctional carcinogen?

Campain JA. Department of Environmental and Radiological Health Sciences, Colorado State University, Ft. Collins, 80523, USA. julie.camapin@colostate.edu PMID: 15146885

Lotsa good quotes here: http://toxsci.oxfordjournals.org/cgi/content/full/79/1/1

Nicotine reduces the incidence of type I diabetes in mice.

Mabley JG, Pacher P, Southan GJ, Salzman AL, Szabó C. Inotek Corporation, Beverly, Massachusetts 01915, USA. jmabley@inotekcorp.com Nicotine has been previously shown to have immunosuppressive actions. Type I diabetes is an autoimmune disease resulting from the specific destruction of the insulin-producing pancreatic beta-cells. Thus, we hypothesized that nicotine may exert protective effects against type I diabetes. The multiple low-dose streptozotocin (MLDS)-induced model and spontaneous nonobese diabetic (NOD) mouse model of type I diabetes were used to assess whether nicotine could prevent this autoimmune disease. Blood glucose levels, diabetes incidence, pancreas insulin content, and cytokine levels were measured in both models of diabetes, both to asses the level of protection exerted by nicotine and to further investigate its mechanism of action. Nicotine treatment reduced the hyperglycemia and incidence of disease in both the MLDS and NOD mouse models of diabetes. Nicotine also protected against the diabetes-induced decrease in pancreatic insulin content observed in both animal models. The pancreatic levels of the Th1 cytokines interleukin (IL)-12, IL-1, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma were increased in both MLDS-induced and spontaneous NOD diabetes, an effect prevented by nicotine treatment. Nicotine treatment increased the pancreatic levels of the Th2 cytokines IL-4 and IL-10. Nicotine treatment reduces the incidence of type I diabetes in two animal models by changing the profile of pancreatic cytokine expression from Th1 to Th2. PMID: 11861793

Immunosuppressive and anti-inflammatory effects of nicotine administered by patch in an animal model.

Kalra R, Singh SP, Pena-Philippides JC, Langley RJ, Razani-Boroujerdi S, Sopori ML. Immunology Division, Lovelace Respiratory Research Institute, 2425 Ridgecrest Dr. SE, Albuquerque, NM 87108, USA. To study the immunological effects of nicotine, there are several rodent models for chronic nicotine administration. These models include subcutaneously implanted miniosmotic pumps, nicotine-spiked drinking water, and self-administration via jugular cannulae. Administration of nicotine via these routes affects the immune system. Smokers frequently use nicotine patches to quit smoking, and the immunological effects of nicotine patches are largely unknown. To determine whether the nicotine patch affects the immune system, nicotine patches were affixed daily onto the backs of Lewis rats for 3 to 4 weeks. The patches efficiently raised the levels of nicotine and cotinine in serum and strongly inhibited the antibody-forming cell response of spleen cells to sheep red blood cells. The nicotine patch also suppressed the concanavalin A-induced T-cell proliferation and mobilization of intracellular Ca(2+) by spleen cells, as well as the fever response of animals to subcutaneous administration of turpentine. Moreover, immunosuppression was associated with chronic activation of protein tyrosine kinase and phospholipase C-gamma1 activities. Thus, in this animal model of nicotine administration, the nicotine patch efficiently raises the levels of nicotine and cotinine in serum and impairs both the immune and inflammatory responses. PMID: 15138183

Sarcoid inflammation can cause elevated CA 125. See the following studies:

A case of ovarian sarcoidosis mimicking malignancy ⁴⁷

Peritoneal sarcoidosis and elevated CA 125 ⁴⁸

Merck says that any peritoneal inflammatory process can increase CA 125 levels.

Sometimes patients do not realize how unreliable tests can be, depending on the circumstances, and how Th1 inflammation can give false impressions in interpreting results.

Read here why CA 125 is not a reliable screening test for ovarian cancer.

This study shows how the menstrual cycle affects CA 125 test results: CA-125 serum concentrations during the menstrual cycle ⁴⁹

Sarcoidosis can cause false positives in cancer tests

Be aware that some of the tests used to identify cancer can be elevated in sarcoidosis, resulting in a “false positive.”

Sarcoidosis associated with an elevated serum CA 125 level: description of a case and a review of the literature ⁵⁰

CA 125 is a glycoprotein expressed by a variety of tissues of mesothelial origin. It has classically been associated with ovarian carcinoma. It has also been reported to be elevated in certain granulomatous conditions. We describe a patient with sarcoidosis and an elevated serum CA 125 level and review the medical literature on this topic.

Conclusions: Peritoneal sarcoidosis may “mimic” ovarian carcinoma in that it may present with peritoneal or abdominal findings and an elevated serum CA 125 level.

~Belinda

A paper by Alan Cantwell, Jr. in JOIMR 2004;2(3):
Acid-Fast Bacteria In-Vivo in Prostate Cancer and the Connection between Prostate Cancer, Other Cancers, and the Kaposi’s Sarcoma Virus

An excellent pioneering paper (Journal of Urology, June, 2005) on acid-fast bacteria in prostate cancer by Ronnie Cohen et.al. out of Perth, Australia, which for the first time suggests that BACTERIA may play a role in prostate cancer:
Propionibacterium Acnes associated with inflammation in radical prostatectomy specimens: A possible link to cancer evolution?

Oct. 17, 2005: Test spots severe prostate cancer

US researchers say there may be a better marker to indicate when a man has a more aggressive form of prostate cancer. Checking for a protein called MDM2 could improve current testing methods which are less than perfect, the Fox Chase Cancer Center team hope.

~BBC News

Feb. 5, 2006: Fatty acids such as those found in corn oil turn on genes that stimulate tumor growth

Omega-6 fatty acids–such as those found in corn oil–caused human prostate tumors in cell culture to grow twice as quickly as tumors to which omega-6 fats had not been added, according to a study conducted at the San Francisco VA Medical Center.

Investigating the reasons for this rapid growth, we discovered that the omega-6 was turning on a dozen inflammatory genes that are known to be important in cancer,” lead author Dr. Millie Hughes-Fulford, from the San Francisco VA Medical Center, said in a statement.

~http://www.news-medical.net/?id=15734

If either of these cancer tests (colonoscopy and PSA) gave a precise answer, a definite prognosis, and a clear treatment path for every possible outcome, then they would be very worthwhile indeed. You can find studies both supporting and denigrating every pathway. Medicine just doesn't have the answers yet, unfortunately.

~Trevor Marshall, PhD

Mar. 13, 2007: PSA 'largely produced by benign prostate disease'

A study published this month provides further evidence against the use of prostate-specific antigen (PSA) as a screening tool for prostate cancer in healthy men.

The research, by a team from Charing Cross Hospital in London, UK, shows that PSA levelcorrelates poorly with prostate volume and supports the hypothesis that PSA is largely produced by benign prostatic hyperplasia (BPH).

Mathias Winkler and colleagues evaluated data on 97 prostates removed at radical cystoprostatectomy. These specimens represented a “fairly random” sample of prostates from asymptomatic men whose prostates had been examined digitally, removed whole, and were amenable to histopathological examination and clinical follow-up.

Prostate cancer was detected in 60% of the specimens, Winkler and colleagues report in BJU International.

Of these tumors, 53% were deemed clinically significant on the basis of Gleason score, tumor stage, surgical margins, perineural invasion, and presence of high-grade prostatic intraepithelial neoplasia.

However, PSA level correlated poorly with tumor volume and did not differ significantly between men with and without prostate cancer (3.1 vs 1.1 ng/ml, p=0.06).

Moreover, after a median follow-up of 3 years, there was just one distant metastasis and seven biochemical recurrences among 35 survivors with prostate cancer. Furthermore, none of the men with clinically insignificant cancers had a biochemical recurrence.

“Most incidental prostate cancers in cystoprostatectomy specimens are significant, contrary to previous analyses, but have little practical importance in terms of oncological outcome,” Winkler and co-authors write.

They say that the lack of correlation between PSA values and presence of prostate cancer represents further supportive evidence that most of the PSA in prostates with cancer is produced by BPH.

“PSA is therefore confirmed as a poor screening tool, which appears to cause a serendipitous detection of prostate cancer,” they conclude. “Meanwhile the search for a better prostate cancer biomarker continues.”

Source: BJU Int 2007; 99: 554­558

~http://www.medwire-news.md/46/65209/Oncology/PSA_largely_produced_by_benign_prostate_disease.html

A paper by Alan Cantwell, Jr. in JOIMR 2003;1(4):1:
Cell-Wall-Deficient Bacteria as a Possible Cause of Basal Cell Carcinoma

ARBs and cancer http://www.sciencedaily.com/releases/2009/06/090601182651.htm

Gene's MP Journey, cancer free for over a year (Sarcoidosis, bladder cancer) Interview with Gene Johnson

I was first diagnosed with Sarcoid in 1977, and like most of you have years of in and out of what seems like remission. To cut a long story short, I finally had a double mastectomy in 2006, and both my breasts came back from the lab, yes, with sarcoid throughout. It shows like a ca in my body.

~Debra

My PSA was through the roof during the first 18 months on the MP (3 - 4 times the safe level). I had a biopsy and a colonoscopy, all were good. As the inflammation in my glands settled so did the PSA. It has fallen well within the safe zone and remained there for nearly 2 years. Hope this gives you some comfort, although my Dr was insistent that I get it checked to be sure.

~Sydney Chris

My prostate and urine flow issues started 20 years ago. I am pretty pleased with all my improvements on MP in that department. Although I never had an elevated PSA my gland was large enough that my urologist wanted to microwave it. Now it is normal size and typical upon rectal exam.

~Polar Bear

Gene Johnson

sarcoidosis, bladder cancer

Read the interview

Interviews of patients with other diseases are also available.

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