Positive Health Online

Key Mechanism behind Cancer Spread is Explained

Scientists have discovered the two key processes that allow cancer cells to change the way they move in order to spread through the body, reports leading scientific journal Cell.[1]

The progression of cancer cells from one part of the body to another (metastasis) is one of the biggest problems in curing cancer, therefore this research brings new hope of future therapies to fight cancer.  The discovery has been made by Dr Victoria Sanz-Moreno in the research team led by Professor Chris Marshall at The Institute of Cancer Research, in work funded by Cancer Research UK.

Professor Marshall says:

"The spreading of cancer cells from one part of the body to another, called metastasis, is one of the biggest causes of death from cancer.  By explaining a key part of that process, our research brings new hope for future therapies to fight cancer.

"The research has found the constant competition between two proteins called 'Rac' and 'Rho' is responsible for allowing the cancer cells to change shape and spread through the body.

"We have shown that cells from melanoma (an aggressive type of skin cancer) are able to rapidly alternate between two different forms of movement where cells have either a round shape or a more stretchy "elongated" shape.

"Together with Dr Erik Sahai and Dr Sophie Pinner at the Cancer Research UK London Research Institute, we have been able to see cells in live tumours carrying out these different forms of movement.  These alternate shapes and ways of moving may enable tumour cells to deal with different situations during cancer spread.  For example, tests indicated that a round-shaped tumour cell may have more durability to survive in our bloodstream than elongated shaped tumour cells."

The Rac process involves a protein called NEDD9, (which has previously been shown to be involved in melanoma metastasis) activating Rac through another protein called DOCK3.  This Rac activity serves a dual purpose, both encouraging the cell to become elongated and simultaneously suppressing the competing Rho activity.  Conversely, when cells adopt the round form a protein activated by Rho, called ARHGAP22, switches off Rac activation.

Dr Victoria Sanz-Moreno says: "Until now the conversion between different types of movement of individual cancer cells had been observed but the key players had not been identified.  We are excited to discover that the amount and the activity of these proteins in the tumour cell regulates its shape and the mechanism for it to move and invade surrounding tissue.  We hope these insights can be used to help develop future therapies".

Dr Lesley Walker, Cancer Research UK director of cancer information, said: "Successful treatment tends to be much more difficult if the cancer has spread.  This exciting study has shed light on some of the key molecules involved in the signalling pathways that encourage cells to move around the body.  Knowing more about how cancer spreads will hopefully lead to the identification of new drug targets which will enable scientists to develop anti-cancer drugs to block these pathways."

Melanoma cells were being studied in this research and their behaviour is also expected to occur in many other types of cancer.  Melanomas are a major target for cancer therapies because although they are the least common, they are the most serious type of skin cancer.  There are about 160,000 new cases of melanoma worldwide each year, including the rarer types that affect the bowel or eye rather than the skin.[2]

Editor's Notes:

[1] "Rac activation and inactivation control plasticity of tumor cell movement". Copies of this paper in Cell are available upon request.  It will appear in the print issue of Cell on 31 October 2008.
[2] Ries LAG, et al, eds. SEER Cancer Statistics Review, 1975-2000. Bethesda, MD: National Cancer Institute; 2003: Tables XVI-1-9.

Further Information

Please contact Cancer Research UK on Tel: 020 7009 8820;   www.cancerresearchuk.org.

Mike Foster, Press and Public Relations Officer, Institute of Cancer Research
Tel: 020 7153 5106  Fax: 020 7153 5261  mike.foster@icr.ac.uk

The Institute of Cancer Research: Royal Cancer Hospital, a charitable Company Limited by Guarantee, Registered in England under Company No. 534147 with its Registered Office at 123 Old Brompton Road, London SW7 3RP.

High Doses of Vitamins Fight Alzheimer's Disease

The news media recently reported that "huge doses of an ordinary vitamin appeared to eliminate memory problems in mice with the rodent equivalent of Alzheimer's disease." They then quickly added that "scientists aren't ready to recommend that people try the vitamin on their own outside of normal doses."[1]

In other words, extra-large amounts of a vitamin are helpful, so don't you take them!

That does not even pass the straight-faced test. So what's the story?

Researchers at the University of California at Irvine gave the human dose equivalent of 2,000 to 3,000 mg of vitamin B3 to mice with Alzheimer's.[2] It worked. Kim Green, one of the researchers, is quoted as saying, "Cognitively, they were cured. They performed as if they'd never developed the disease."

Specifically, the study employed large amounts of nicotinamide, the vitamin B3 widely found in foods such as meat, poultry, fish, nuts and seeds. Nicotinamide is also the form of niacin found, in far greater quantity, in dietary supplements. It is more commonly known as niacinamide. It is inexpensive and its safety is long established. The most common side effect of niacinamide in very high doses is nausea. This can be eliminated by taking less, by using regular niacin instead, which may cause a warm flush, or choosing inositol hexaniacinate, which does not. They are all vitamin B3.

HealthDay Reporter mentioned how cheap the vitamin is; the study authors "bought a year's supply for $30" and noted that it "appears to be safe" Even so, one author said that "I wouldn't advocate people rush out and eat grams of this stuff each day."[1]

The BBC quoted Rebecca Wood, Chief Executive of the UK Alzheimer's Research Trust, who said, "Until the human research was completed, people should not start taking the supplement. . . . people should be wary about changing their diet or taking supplements. In high doses vitamin B3 can be toxic."[3]

The Irish Times reiterated it: "People have been cautioned about rushing out to buy high dose vitamin B3 supplements in an attempt to prevent memory loss . . . The warnings came today one day on from the announcement . . .Vitamins in high doses can be toxic."[4]

Their choice of words is quaint but hardly accurate. There is no wild "rush;" half of the population already takes food supplements. And as for "toxic," niacin isn't. Canadian psychiatrist Abram Hoffer MD asserts that it is actually remarkably safe. "There have been no deaths from niacin supplements," Dr. Hoffer says. "The LD 50 (the dosage that would kill half of those taking it) for dogs is 5,000-6,000 milligrams per kilogram body weight. That is equivalent to almost a pound of niacin per day for a human. No human takes 375,000 milligrams of niacin a day. They would be nauseous long before reaching a harmful dose." Dr. Hoffer conducted the first double-blind, placebo-controlled clinical trials of niacin. He adds, "Niacin is not liver toxic. Niacin therapy increases liver function tests. But this elevation means that the liver is active. It does not indicate an underlying liver pathology."

The medical literature repeatedly confirms niacin's safety. Indeed, for over 50 years, nutritional (orthomolecular) physicians have used vitamin B3 in doses as high as tens of thousands of milligrams per day. Cardiologists frequently give patients thousands of milligrams of niacin daily to lower cholesterol. Niacin is preferred because its safety margin is so very large. The American Association of Poison Control Centers' Toxic Exposure Surveillance System annual reports indicates there is not even one death per year due to niacin in any of its forms.[5]

One the other hand, there are 140,000 deaths annually attributable to properly prescribed prescription drugs.[6] And this figure is just for one year, and just for the USA. Furthermore, when overdoses, incorrect prescription, and adverse drug interactions are figured in, total drug fatalities number over a quarter of a million dead. Each year.

The BBC's curious mention that we should even be "wary about changing our diets" is especially odd. More and more scientists think our much-in-need-of-improvement diets are what contribute more than anything to developing Alzheimer's. "There appears to be a statistically significant link between a low dietary intake of niacin and a high risk of developing Alzheimer's disease. A study of the niacin intake of 6158 Chicago residents 65 years of age or older established that the lower the daily intake of niacin, the greater the risk of becoming an Alzheimer's disease patient." The group with the highest daily intake of niacin had a 70 percent decrease in incidence of this disease compared to the lowest group. "The most compelling evidence to date is that early memory loss can be reversed by the ascorbate (vitamin C) minerals. Greater Alzheimer's disease risk also has been linked to low dietary intake of vitamin E and of fish."[7]

Nutrient deficiency of long standing may create a nutrient dependency. A nutrient dependency is an exaggerated need for the missing nutrient, a need not met by dietary intakes or even by low-dose supplementation. Robert P Heaney MD uses the term "long latency deficiency diseases" to describe illnesses that fit this description. He writes: "Inadequate intakes of many nutrients are now recognized as contributing to several of the major chronic diseases that affect the populations of the industrialized nations. Often taking many years to manifest themselves, these disease outcomes should be thought of as long-latency deficiency diseases. . . Because the intakes required to prevent many of the long-latency disorders are higher than those required to prevent the respective index diseases, recommendations based solely on preventing the index diseases are no longer biologically defensible."[8] Where pathology already exists, unusually large quantities of vitamins may be needed to repair damaged tissue. Thirty-five years ago, in another paper, Hoffer wrote: "The borderline between vitamin deficiency and vitamin-dependency conditions is merely a quantitative one when one considers prevention and cure."[9]

As there is no recognized cure for Alzheimer's, prevention is vital. In their article, the Irish Times does admit that "Healthy mice fed the vitamins also outperformed mice on a normal diet" and quoted study co-author Frank LaFerla saying that "This suggests that not only is it good for Alzheimer's disease, but if normal people take it, some aspects of their memory might improve."(4) And study author Green added, "If we combine this with other things already out there, we'd probably see a large effect."

The US Alzheimer's Association's Dr. Ralph Nixon has said that previous research has suggested that vitamins such as vitamin E, vitamin C and vitamin B12 may help people lower their risk of developing Alzheimer's disease. At their website (although you have to search for it), the Alzheimer's Association says, "Vitamins may be helpful. There is some indication that vitamins, such as vitamin E, or vitamins E and C together, vitamin B12 and folate may be important in lowering your risk of developing Alzheimer's. . . One large federally funded study[10] showed that vitamin E slightly delayed loss of ability to carry out daily activities and placement in residential care."

But overall, at their website www.alz.org/index.asp the Alzheimer's Association has strikingly little to say about vitamins, and they hasten to tell people that "No one should use vitamin E to treat Alzheimer's disease except under the supervision of a physician." (www.alz.org/alzheimers_disease_10428.asp) "They write as if these safe vitamins are dangerous drugs, not be used without a doctor's consent," comments Dr. Hoffer. "I have been using them for decades."

Niacin and nerves go together. Orthomolecular physicians have found niacin and other nutrients to be an effective treatment for obsessive compulsive disorder, anxiety, bipolar disorder, depression, psychotic behaviour, and schizophrenia. New research confirms that niacinamide (the same form of B3 used in the Alzheimer's research) "profoundly prevents the degeneration of demyelinated axons and improves the behavioural deficits" in animals with an illness very similar to multiple sclerosis.[11]

A measure of journalistic caution is understandable, especially with ever-new promises for pharmaceutical products. Drugs routinely used to treat Alzheimer's Disease have had a disappointing, even dismal success rate. So when nutrition may be the better answer, foot-dragging is inexplicable, even inexcusable. Nutrients are vastly safer than drugs. Unjustified, needlessly negative opinionating is out of place. Over 5 million Americans now have Alzheimer's disease, and the number is estimated to reach 14 million by 2050. Potentially, 9 million people would benefit later from niacin now.

"Man is a food-dependent creature," wrote University of Alabama professor of medicine Emanuel Cheraskin, M.D.. "If you don't feed him, he will die. If you feed him improperly, part of him will die."

When that part is the brain, it is dangerous to delay the use of optimum nutrition.

References:

[1] Vitamin Holds Promise for Alzheimer's Disease. Randy Dotinga, HealthDay Reporter, Nov 5, 2008.
www.washingtonpost.com/wp-dyn/content/article/2008/11/05/AR2008110502796.html  and also http://health.yahoo.com/news/healthday/vitaminholdspromiseforalzheimersdisease.html  
[2] Green KN, Steffan JS, Martinez-Coria H, Sun X, Schreiber SS, Thompson LM, LaFerla FM. Nicotinamide restores cognition in Alzheimer's disease transgenic mice via a mechanism involving sirtuin inhibition and selective reduction of Thr231-phosphotau. J Neurosci. 2008 Nov 5;28(45):11500-10.
[3] BBC, 5 Nov 2008. http://news.bbc.co.uk/2/hi/health/7710365.stm  
[4] Donnellan E. Caution urged over using vitamin B3 to treat Alzheimer's. Wed, Nov 05, 2008. www.irishtimes.com/newspaper/breaking/2008/1105/breaking91.htm  
[5] Annual Reports of the American Association of Poison Control Centers' National Poisoning and Exposure Database (formerly known as the Toxic Exposure Surveillance System). AAPCC, 3201 New Mexico Avenue, Ste. 330, Washington, DC 20016. Download any report from1983-2006 at www.aapcc.org/dnn/NPDS/AnnualReports/tabid/125/Default.aspx  free of charge. The 'Vitamin' category is usually near the end of the report.
[6] Classen DC, Pestotnik SL, Evans RS, Lloyd JF, Burke JP. Adverse drug events in hospitalized patients. Excess length of stay, extra costs, and attributable mortality. JAMA. 1997 Jan 22-29;277(4):301-6.
[7] 21. Hoffer A and Foster HD. Feel Better, Live Longer With Vitamin B-3: Nutrient Deficiency and Dependency. CCNM Press, 2007. ISBN-10: 1897025246; ISBN-13: 978-1897025246. Also: Foster HD. What Really Causes Alzheimer's Disease. Trafford, 2004. ISBN 1-4120-4921-0.
[8] Heaney RP: Long-latency deficiency disease: insights from calcium and vitamin D. Am J Clin Nutr. 2003; Nov; 78(5):912-9.
[9] Hoffer A. Mechanism of action of nicotinic acid and nicotinamide in the treatment of schizophrenia. In: Hawkins D and Pauling L: Orthomolecular Psychiatry: Treatment of Schizophrenia. San Francisco: W.H. Freeman. 1973; p. 202-262.
[10] Sano M, Ernesto C, Thomas RG et al. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. The Alzheimer's Disease Cooperative Study. N Engl J Med. 1997 Apr 24;336(17):1216-22.
[11] Kaneko S, Wang J, Kaneko M, Yiu G, Hurrell JM, Chitnis T, Khoury SJ, He Z. Protecting axonal degeneration by increasing nicotinamide adenine dinucleotide levels in experimental autoimmune encephalomyelitis models. J Neurosci. 2006 Sep 20;26(38):9794-804. www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=pubmed  See also: Vitamins fight multiple sclerosis. Orthomolecular Medicine News Service, October 4, 2006.

For More Information:

A complete copy of Dr. Harold D. Foster's What Really Causes Alzheimer's Disease is available in PDF format, free of charge: www.hdfoster.com/Foster_Alzheimers.pdf  
To access a free archive of peer-reviewed medical journal papers on the safety and efficacy of vitamin therapy: http://orthomolecular.org/library/jom/  
Review of nutritional approaches to Alzheimer's Disease: www.doctoryourself.com/alzheimer.html  

Additional Reading:

Klenner FR. Response of peripheral and central nerve pathology to mega-doses of the vitamin B-complex and other metabolites. Journal of Applied Nutrition, 1973. www.tldp.com/issue/11_00/klenner.htm  
Morris MC, Evans DA, Bienias JL, Tangney CC, Bennett DA, Aggarwal N, Wilson RS, and Scherr PA. Dietary intake of antioxidant nutrients and the risk of incident Alzheimer's disease in a biracial community study. Journal of the American Medical Association, 2002. 287(24), 3230-3237.
Morris MC, Evans DA, Bienias PA, Scherr A, Tangney CC, Hebert LE, Bennett DA, Wilson RS, and Aggarwal N. Dietary Niacin and the Risk of Incident Alzheimer's Disease and of Cognitive Decline. J Neurology, Psychiatry 2004; 75: 1093-1099.
Bobkova NV. The impact of mineral ascorbates on memory loss. Paper presented at the III World Congress on Vitamin C, 2001, Committee for World Health, Victoria, BC, Canada.
Galeev A, Kazakova A, Zherebker E, Dana E, and Dana R. Mineral ascorbates improve memory and cognitive functions in older individuals with pre-Alzheimer's symptoms. Copy of paper given to authors by R. Dana and E. Dana, Committee for World Health, 20331 Lake Forest Drive, Suite C-15, Lake Forest, California 92630, USA.
Bobkova NV, Nesterova IV, Dana E, Nesterov VI, Aleksandrova IIu, Medvinskaia NI, and Samokhia AN (2003). Morpho-functional changes of neurons in temporal cortex in comparison with spatial memory in bulbectomized mice after treatment with minerals and ascorbates. Morfologiia, 123(3), 27-31. [In Russian]
Engelhart MJ, Geerlings MI, Ruitenberg A, van Swieten JC, Hofman A, and Witteman JC (2002). Dietary intake of antioxidants and risk of Alzheimer's disease: Food for thought. Journal of the American Medical Association, 287(24), 3223-3229.
Grant WB. Dietary links to Alzheimer's disease: 1999 update. Journal of Alzheimer's Disease, 1999, 1(4,5), 197-201.
Barberger-Gateau P, Letenneur L, Deschamps V, Pérès K, Jean-François Dartigues JF, and Renaud S (2002). Fish, meat, and risk of dementia: Cohort study. British Medical Journal, 325, 932-933.
Vogiatzoglou A, Refsum H, Johnston C, Smith SM, Bradley KM, de Jager C, Budge MM, Smith AD. Vitamin B12 status and rate of brain volume loss in community-dwelling elderly. Neurology. 2008 Sep 9;71(11):826-32.

Further Information

Orthomolecular medicine uses safe, effective nutritional therapy to fight illness. For more information: www.orthomolecular.org   Andrew W Saul PhD Editor  omns@orthomolecular.org  

Note

Copyright 2008 International Schizophrenia Foundation www.orthomed.org/isf/isf.html  
Reprinted with permission from ISF.  International Schizophrenia Foundation, 16 Florence Avenue, Toronto, Ontario, Canada M2N 1E9. Fax: 001 416 733-2352; centre@orthomed.org     www.orthomed.org

Vitamin E Prevents Lung Cancer

Researchers at the University of Texas Anderson Cancer Center have found that taking more vitamin E substantially reduces lung cancer. Their new study shows that people consuming the highest amounts of vitamin E had the greatest benefit. When they compared persons taking the most vitamin E with those taking the least, there was a 61% reduction in lung cancer risk.[1]

Lung cancer is the most prevalent form of cancer on earth; over 1.3 million people are diagnosed with it each year. With medical treatment, survival rates are "consistently poor," says Cancer Research UK. Lung cancer kills nearly 1.2 million per year. It accounts for 12% of all cancers, but results in 18% of all cancer deaths.[2] Anything that can reduce these dismal facts is important news . . .very important. Yet the mainstream media have virtually ignored vitamin E's important role as a cancer fighter.

A sixty-one percent reduction in lung cancer with vitamin E? How could the news media have missed this one?

The news media probably did not miss it: they simply did not report it. They are biased. You can see for yourself what bias there is. Try a 'Google' search for any of the major newspapers or broadcast media, using the name of the news organization along with the phrase "vitamin E lung cancer." When you do, you will find that it will quickly bring up previous items alleging that vitamin E might (somehow) increase cancer risk. You will find little or nothing at all on how vitamin E prevents cancer. Indeed, the bias is so strong that even a qualified search for "increased vitamin E reduces lung cancer" will still, and preferentially, bring up media coverage alleging that vitamin E is harmful. Negative reporting sells newspapers and pulls in viewing audiences. The old editors' adage must still be true: "If it bleeds, it leads."

Here's more positive vitamin E cancer research that the media 'missed'. A study in 2002 looked at patients with colon cancer "who received a daily dose of 750 mg of vitamin E during a period of 2 weeks. Short-term supplementation with high doses of dietary vitamin E leads to increased CD4:CD8 ratios and to enhanced capacity by their T cells to produce the T helper 1 cytokines interleukin 2 and IFN-gamma. In 10 of 12 patients, an increase of 10% or more (average, 22%) in the number of T cells producing interleukin 2 was seen after 2 weeks of vitamin E supplementation." The authors concluded that "dietary vitamin E may be used to improve the immune functions in patients with advanced cancer." That improvement was achieved in a mere two weeks merits special attention.[3]

Was it on the news? Did you hear about how high doses of vitamin E help cancer patients' immune systems in only two weeks? Why not? Might the answer possibly have anything to do with money? One cannot watch television or read a magazine or newspaper without it being obvious that drug company cash is one of the media's very largest sources of revenue. Given where their advertising income comes from, it is hardly a big surprise that media reporting on vitamins is biased. Well-publicized vitamin scares feed the pharmaceutical industry. Successful reports of safe, inexpensive vitamin therapy do not.

One commentator has observed that pharmaceutical and other "corporations marshal huge public relations efforts on behalf of their agendas. In the United States the 170,000 public relations employees whose job it is to manipulate news, public opinion and public policy in the interests of their clients outnumber news reporters by 40,000."[4] Another commentator wrote that "Janine Jackson of Fairness and Accuracy in Reporting (FAIR), a news media watchdog group, told the American Free Press that 60 percent of journalists surveyed by FAIR admitted that advertisers "try to change stories (and) there is an overwhelming influence of corporations and advertisers" on broadcast and print news reporting."[5]

Drug companies don't have any drug that can reduce lung cancer risk by 61%. If they did, you would have heard all about it in their advertisements. And it would be all over the news. Positive drug studies get the headlines. Positive vitamin studies rarely do. This is an enormous public health problem with enormous consequences. A cynic might say that press and television coverage of a vitamin study tends to be inversely proportionate to the study's clinical usefulness. Truly valuable research does not scare people; it helps people get well. It would be difficult to identify anything more helpful than actively reporting the story when a vitamin is shown to reduce lung cancer by 61%.

The good news about how important high quantities of vitamin E are in combating cancer is not arising out of nowhere. A US National Library of Medicine MEDLINE search will bring up over 3,000 studies on the subject, some dating back to 1946. By the early 1950s, research clearly supported the use of vitamin E against cancer.[6] Before 1960, vitamin E was shown to reduce the side effects of radiation cancer treatment.[7] In reviewing vitamin E research, one notes that the high-dose studies got the best results.

Vitamin E is not the sure cure for cancer. It is not certain prevention, either. Stopping cigarette smoking is essential. But vitamin E is part of the solution, and we need more of it. An independent panel of physicians and researchers(8) has recently called for increasing the daily recommended intake for vitamin E to 200 IU. The present US RDA/DRI is a mere 15-20 IU/day.

It is time to raise it. A lot.

References:

[1] Mahabir S, Schendel K, Dong YQ, Barrera SL, Spitz MR, Forman MR. Dietary alpha-, beta-, gamma- and delta-tocopherols in lung cancer risk. Int J Cancer. 2008 Sep 1;123(5):1173-80.
[2] http://info.cancerresearchuk.org/cancerstats/geographic/world/commoncancers/  
[3] Malmberg KJ, Lenkei R, Petersson M et al. A short-term dietary supplementation of high doses of vitamin E increases T helper 1 cytokine production in patients with advanced colorectal cancer. Clin Cancer Res. 2002 Jun; 8(6):1772-8.
[4] Robbins R. Global problems and the culture of capitalism. Allyn and Bacon, 1999, p 138. http://www.globalissues.org/article/160/media-and-advertising  
[5] Prestage J. Mainstream journalism: Shredding the First Amendment. Online Journal, November 7, 2002. http://www.globalissues.org/article/160/media-and-advertising  
[6] Telford IR. The influence of alpha tocopherol on lung tumors in strain A mice. Tex Rep Biol Med. 1955;13(3):515-21. Swick RW, Baumann CA, Miller WL Jr, Rumsfeld HW Jr. Tocopherol in tumor tissues and effects of tocopherol on the development of liver tumors. Cancer Res. 1951 Dec;11(12):948-53.
[7] Fischer W. [The protective effect of tocopherol against toxic phenomena connected with the roentgen irradiation of mammary carcinoma.] Munch Med Wochenschr. 1959 Sep 4;101:1487-8. German. Also: Sabatini C, Balli L, Tagliavini R. [Effects of vitamin E and testosterone in comparisons of skin exposed to high doses of roentgen rays administered by semi-contact technic.] Riforma Med. 1955 Apr 30;69(18):Suppl, 1-4. Italian. See also: Graham JB, Graham RM. Enhanced effectiveness of radiotherapy in cancer of the uterine cervix. Surg Forum. 1953;(38th Congress):332-8.
[8] Doctors say, Raise the RDAs now. Orthomolecular Medicine News Service, October 30, 2007. http://orthomolecular.org/resources/omns/v03n10.shtml  

Many full-text nutrition and vitamin therapy research papers are posted for free access at http://orthomolecular.org/library/jom  .

Further Information

Orthomolecular medicine uses safe, effective nutritional therapy to fight illness. For more information  www.orthomolecular.org  
Andrew W Saul PhD Editor  omns@orthomolecular.org