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A macrophageAs an organisation dedicated to beating cancer, we have a deep-rooted interest in any new research developments that could lead to new, more effective treatments for the disease.

So when we received an enquiry from a supporter about an article entitled “Cancer cured for good” by Bill Sardi and Timothy Hubbell* we were intrigued. The article talks about research by Nobuto Yamamoto in the US, looking at a protein called Gc-MAF (aka GcMAF). His published studies appear to show that injections of very small amounts of Gc-MAF can “cure” people with breast, bowel and prostate cancer.

According to the article, “It works 100% of the time to eradicate cancer completely, and cancer does not recur even years later.” Could this be the so-called ‘cure for cancer’ that we’ve been searching for all these years?

Sadly – as with so many things in life – if it sounds too good to be true it probably is. Let’s explore a bit further.

What’s the idea behind it?

Dr Yamamoto studies the immune system – the highly complex network of cells that helps to keep us healthy. The cells of the immune system – white blood cells – fight bacterial and viral infections because they can recognise and attack these ‘foreign’ invaders . But they’re not so good at tackling cancer, since tumours grow from our own cells and have clever mechanisms to ’cloak’ them from immune attack.

Macrophages (meaning “big eaters” in Greek) are an important type of white blood cell. They patrol the body, eating up foreign invaders and dead cells. They also help to alert other immune cells to the presence of infections.

Macrophages can be stirred into action by a small sugar-coated protein (glycoprotein) called Gc-MAF, short for Gc Macrophage Activating Factor, which is produced by the body. But the production of Gc-MAF is blocked by an enzyme called Nagalase (alpha-N-acetylgalactosaminidase), produced by many cancers. This is one of the mechanisms that helps tumours evade the immune system.

Yamamoto’s theory is that injecting cancer patients with Gc-MAF should activate their macrophages to fight the cancer. He tested it back in 1997 in a paper published in the journal Cancer Research, showing that injecting Gc-MAF into mice transplanted with cancer cells could improve their survival from around 16 days to around 35.

But the treatment did not ‘cure’ the cancer, as the cancer cells continued to multiply, eventually killing the mice.

Clinical trials

Fast-forward a few years, to the publication of three papers detailing the results of clinical trials of Gc-MAF carried out by Yamamoto, testing the treatment on patients with breast, bowel and prostate cancer.

Note: The breast cancer paper (Yamamoto et al Int J Cancer 2008) has now been retracted, due to various concerns with the work. Read more on the RetractionWatch blog. [Updated KA 25/07/14] The bowel cancer paper (Yamamoto et al Cancer Immunology Immunotherapy 2008) has also now been retracted. This letter details some of the concerns about the work. [Updated KA 09/10/14]

The results appear to be startling – all the patients on the trials are ‘cured’ of cancer. Surely this is an amazing breakthrough?

Put bluntly, no it isn’t. There are significant scientific problems with the trials. For a start, all the studies are very small, involving fewer than twenty patients in each – rather than the thousands needed to make the sort of claims mentioned above.

Next, all the patients involved had received standard treatment for their cancer, including surgery, chemotherapy and/or radiotherapy. This is a somewhat unorthodox design for a trial of this kind, because it makes it very difficult to tell if any successes are due to the new drug, or the more conventional treatments.

On top of this, the researchers didn’t actually monitor the progress of tumours in the patients, and provide no clinical information about them. Instead they opt to measure levels of Nagalase in the blood, rather than looking at any standard established markers for cancer.

For example, in the case of the breast cancer patients, there is no detail about their “TNM” (tumour, node, metastasis) status. This is a standard measure of how far a patient’s cancer has spread, and is used to calculate the likelihood that it will return.

Furthermore, the researchers didn’t do any tests to show that injected Gc-MAF was actually activating macrophages in the patients’ blood, or even working in the way that they expect. There is no information about levels of cytokines – the proteins produced by immune cells when they are activated – or analysis of the patients’ immune cells.

Perhaps most significantly, there are no controls – untreated patients for comparison – and the studies only followed the patients for a few years. We have no way of telling whether their cancers were growing again, or had been successfully treated, and whether this was due to Gc-MAF or the other treatment they had received.

Given that 80 per cent of all women with breast cancer survive for at least 5 years, an uncontrolled study showing that 16 women of unknown TNM status survive for at least 4 years is no great shakes, scientifically speaking.

Further problems

Another telling point is the type of journal in which the research was published. If this research was truly groundbreaking, and pointed the way to a cure for cancer, then the research would likely be found in top-tier ’high-impact’ medical journals journals like The Lancet, The New England Journal of Medicine or the Journal of the American Medical Association.

And finally, virtually all the references in the papers are to other papers published by Yamamoto and his team. If Gc-MAF was indeed a promising candidate for a successful cancer treatment, you’d expect plenty of other research to show the same thing. Scientists are usually quick to spot promising, emerging fields of research and jump on the bandwagon.

The poor quality of scientific papers supporting GcMAF is discussed here on the Scholarly Open Access blog. [Updated KA 25/07/14]

Is there hope?

Although this particular approach isn’t all it’s hyped up to be, harnessing the power of immune system could be a very potent way to treat cancer. We’ve blogged many times already on high-quality research into immunotherapy (for example here, here, here and here)

And many Cancer Research UK-funded scientists are also working in this field. For example, Professor Fran Balkwill and her team are working on ways to trick macrophages and other immune cells into attacking cancer cells.

In 2014, researchers in Israel started a small-scale early-stage clinical trial looking at the dosage and safety of GcMAF in cancer patients. The full protocol and further information are available on the Clinicaltrials.gov register[Updated KA 25/07/14]

To sum up

The advent of the internet has led to a wild proliferation of stories of ‘miracle cures’ for cancer – virtually all of which are based on shaky (or zero) science.

Some companies are selling Gc-MAF for use by cancer patients. This treatment is not approved or licensed in the UK for treating cancer or any 0ther disease. Given that there is no solid scientific evidence to show that the treatment is safe or effective, we would not recommend that cancer patients use it. [Updated KA 25/07/14]

Cancer is an extremely complex disease. In fact, it is more than 200 distinct diseases, each requiring different treatment. And the success of treatment depends on many things, including the genetic make-up of the tumour, the stage of diagnosis, and how aggressive the cancer is.

To suggest that there is a ‘magic bullet’ that cures all cancers is simplistic in the extreme.

Kat

With thanks to Thorsten Hagemann at the Institute of Cancer, Barts and The London School of Medicine.

Read more:

*Cancer Research UK is not responsible for the content of external websites. This is not an endorsement of the website by Cancer Research UK.

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Comments

Henry Scowcroft June 30, 2009

Regretfully, we have closed comments on this thread.

This is not to intentionally to stifle debate around this issue, which is obviously something many feel passionately about (including ourselves). As a charity dedicated to evidence-based science, we absolutely feel that debate and discussion of scientific issues is key to improving cancer treatment and awareness of issues surrounding the disease. That is why we started writing this blog.

Recently, however, we have had to increasingly delete and moderate attempts to post links to websites selling Gc-MAF, and to promote its use to treat cancer. Neither of these is something we’re comfortable with, given the current state of evidence surrounding Gc-MAF. As we’ve repeatedly said above, we believe there are substantial shortcomings with the evidence base around this substance, and until these are clarified, we cannot recommend anyone, anywhere, considers it as a serious treatment option.

We hope you understand, and apologies once again.

Henry, Kat and Ed

Kat Arney May 29, 2009

Thanks for your comment. We appreciate the interest in Yamamoto’s claims about HIV, but as publicly-funded charity dedicated to cancer research, our work must necessarily focus on cancer.

We do not directly commission research projects – our funds are awarded through a competitive grant process http://science.cancerresearchuk.org/gapp/ If a researcher wished to carry out work in the UK on Gc-MAF’s potential for treating cancer, they would need to apply to the appropriate Cancer Research UK committee. Their application would then be judged by a panel of national and international experts – as all grant applications are. We will only fund work that is highly competitive, and at the forefront of research into cancer.

Kat

visonetto May 29, 2009

The Hiv Eradication article pubblished by prof. Yamamoto on January 2009 on the scientific Journal Medical Virology, has had little feedback…better say, no feedback at all even by the national and international press too.
This fact is very strange!
Only some associations have posted the news on their home-pages but the news has dropped away without any feedback.
Some Hiv+ people have activated a series of initiatives to contact the directors of the JMV, responsable of the publication.
The publication of Prof. Yamamoto is rich of significant data and descriptive tables about the research and are of a big impact.
The directors of the magazine, Prof. Zuckerman and Prof. Mahny have answered to the questions, guaranteeing the validaty of the data, eventhough in an elusory way, but at the same time threatening to sue us without any reason. The questions were legitimate and politely done!
Is it possible that nobody wants to comment this article of such a big impact!?
Anyway it has been prepared the following e-mail and sent to the most prestigious agencies.

Dear director of Aids Operative Centre.
more than 4 months ago has been possible to notice the publishing, on the scientific Jornal Medical Virology, an article on HIV eradication by Prof. Yamamoto, explaining the way he obtained the Hiv eradication in only 18 weeks by injecting, weekly, 100ng GcMAF, an activating factor of macrophages obtained by the Gc Protein. This is shown by a fully successfull experiment, done in 2002 on 15 assintomatic Hiv+ patients and non anemic one; these patients have been healthy without having a viral feedback (HIV-RNA, HIV-DNA) and immune alterations such as CD4, CD8 and their percentage absolutely normal) in more than seven years (J. Med. Virol. 81:16-26, 2009).

We have been trying to inquire with the help of the associations, specialists and even embassys without having a feedback, particularly:
1 – [authorised ethic committees]
2 – [centres and patients]
3 – [contacts with the authors]
4 – [contacts with the directors of JMV]
….

Now, since the issue continues to cause serious disturbance among all the Hiv+, and we are not in the best possible conditions, we ask to You and to Your Institution, authority of national importance, to clear up the points above, in order to ascertain whether we are faced with a falsely clamorous scientific discovery or a true one.
Certainly we would like to see confirmed the latter one. We are convinced that you would put under exam the GcMAF, a low-cost molecule and of an easy preparation, for further clinical trial in case of the results of Prof Yamamoto would be authentic. This would represent the salvation of millions of Hiv+ people all over the world.
Dispite the disappointment in case the trial is not true, we are greatful to You for having provided to us an answer.
Hopefully in an acceptance of our request, we thank and cordially greet.

An Hiv+ patient.

John Page April 15, 2009

Alot of smart people say cancer is 100 different deseases………I don’t think so. In my heart its one desease that may attack 100 different places.The idea that the immune system in some people isn’t doing its job, makes sence to me.

By the way my daughters chemo was changed and her second round was not as bad. None the less we are also taking extra measures ie. diet no sugars , ozone treatments….ground up flax seed, better water. Maybe zeolite coming next.

Sure hope this Gc-MAF gets off the ground and get rid of chemo……like DDT it should be banned!

northsouth March 30, 2009

Are macrophages the strongest human’s weapon to beat the cancer ? ..probably yes.

Dr Zengh Cui and Mark Willingham

Dr Zengh Cui research makes Yamamoto’s MAF declaration stronger and stronger.

http://www1.wfubmc.edu/tumorbio/srmouse/index.htm

More recent studies, described in the May 8, 2006, Proceedings of the National Academy of Science USA, demonstrated the ability to cure cancer in normal mice by transferring purified immune cells from the cancer-resistant mice. These newer studies show that specific types of innate immune cells, such as macrophages, can migrate to the site of cancer in a normal mice and selectively kill all of the cancer cells without harming normal cells. Such studies suggest that this type of mechanism might one day be able to help design a new strategy for cancer therapy.

Transferable anticancer innate immunity in spontaneous regression/complete resistance mice

Amy M. Hicks*, Gregory Riedlinger†, Mark C. Willingham*, Martha A. Alexander-Miller‡, C. Von Kap-Herr§, Mark J. Pettenati§, Anne M. Sanders*, Holly M. Weir*, Wei Du*, Joseph Kim*, Andrew J. G. Simpson¶, Lloyd J. Old¶,‖, and Zheng Cui*,‖
+Author Affiliations

Departments of *Pathology,
†Cancer Biology, and
‡Microbiology and Immunology, and
§Department of Pediatrics, Section on Medical Genetics, Wake Forest University School of Medicine, Winston-Salem, NC 27157; and
¶Ludwig Institute for Cancer Research, New York, NY 10158
Contributed by Lloyd J. Old, March 28, 2006

Abstract
Spontaneous regression/complete resistance (SR/CR) mice resist very high doses of cancer cells that are lethal to WT mice even at low doses. In this study, we show that this resistance is mediated by rapid infiltration of leukocytes, mostly of innate immunity, in both primary and repeated challenges. Formation of rosettes with infiltrating natural killer cells, neutrophils, and macrophages was required for the subsequent destruction of cancer cells through rapid cytolysis. Highly purified natural killer cells, macrophages, and neutrophils from the SR/CR mice independently killed cancer cells in vitro. The independent killing activity by each subset of effector cells is consistent with the observation that the resistance was abolished by depleting total infiltrating leukocytes but not by depleting only one or two subsets of leukocytes. The resistance was completely transferable to WT recipient mice through SR/CR splenocytes, bone marrow cells, or enriched peritoneal macrophages, either for prevention against subsequent cancer challenges or eradication of established malignancy at distant sites.

alcohol detox March 26, 2009

Many people are being cured of cancer by other means.
Yamamoto’s theory is that injecting cancer patients with Gc-MAF should activate their macrophages to fight the cancer. He tested it back in 1997 in a paper published in the journal Cancer Research, showing that injecting Gc-MAF into mice transplanted with cancer cells could improve their survival from around 16 days to around 35.

Kat Arney March 18, 2009

I’m very sorry to hear about your daughter. There is an awful lot of information out there on the internet about cancer treatments and cures, and not all of it is reliable. Many so-called “cures” are not based on sound science and have not been tested in clinical trials – there is no guarantee they will do any good, and at worst they could be harmful.

There’s lots more information about alternative and complementary treatments on our CancerHelp UK website: http://cancerhelp.cancerresearchuk.org/about-cancer/treatment/complementary-alternative/

I would also strongly recommend that you look at Quackwatch to see if they have anything to say about potential avenues you may be looking at, to see if they could be dangerous, fraudulent or simply ineffective:
http://www.quackwatch.com/00AboutQuackwatch/altseek.html

Best wishes to you and your family,
Kat

John Page March 17, 2009

Thanks…..Kat Arney

But now Im back to square one….I don’t suppose I can get this Gc-MAF.

My daughter’s blood count went down to .3 after her first chemo. Im looking outside the box for sure….she doesn’t want chemo again.

What now….some say go to Mexico others Mushroom extract….some Keelation using Zeolite to purge the body of metals.

Gc-MAF looked like my best bet!