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Old 09-12-2008, 02:40 PM   #1
Rich66
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Immunotherapy of metastatic breast cancer patients with vitamin D-binding protein-der

Immunotherapy of metastatic breast cancer patients with vitamin D-binding protein-derived macrophage activating factor (GcMAF).

Yamamoto N, Suyama H, Yamamoto N, Ushijima N.
Division of Cancer Immunology and Molecular Biology, Socrates Institute for Therapeutic Immunology, Philadelphia, PA 19126-3305, USA. nobutoyama@verizon.net
Serum vitamin D3-binding protein (Gc protein) is the precursor for the principal macrophage activating factor (MAF). The MAF precursor activity of serum Gc protein of breast cancer patients was lost or reduced because Gc protein was deglycosylated by serum alpha-N-acetylgalactosaminidase (Nagalase) secreted from cancerous cells. Patient serum Nagalase activity is proportional to tumor burden. The deglycosylated Gc protein cannot be converted to MAF, resulting in no macrophage activation and immunosuppression. Stepwise incubation of purified Gc protein with immobilized beta-galactosidase and sialidase generated probably the most potent macrophage activating factor (termed GcMAF) ever discovered, which produces no adverse effect in humans. Macrophages treated in vitro with GcMAF (100 pg/ml) are highly tumoricidal to mammary adenocarcinomas. Efficacy of GcMAF for treatment of metastatic breast cancer was investigated with 16 nonanemic patients who received weekly administration of GcMAF (100 ng). As GcMAF therapy progresses, the MAF precursor activity of patient Gc protein increased with a concomitant decrease in serum Nagalase. Because of proportionality of serum Nagalase activity to tumor burden, the time course progress of GcMAF therapy was assessed by serum Nagalase activity as a prognostic index. These patients had the initial Nagalase activities ranging from 2.32 to 6.28 nmole/min/mg protein. After about 16-22 administrations (approximately 3.5-5 months) of GcMAF, these patients had insignificantly low serum enzyme levels equivalent to healthy control enzyme levels, ranging from 0.38 to 0.63 nmole/min/mg protein, indicating eradication of the tumors. This therapeutic procedure resulted in no recurrence for more than 4 years. Copyright 2007 Wiley-Liss, Inc.
PMID: 17935130 [PubMed - indexed for MEDLINE
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Old 09-12-2008, 03:00 PM   #2
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a less technical read on this. (is this bogus?)

Real Help for Cancer?
by Bill Sardi and Timothy Hubbell
by Bill Sardi and Timothy Hubbell


DIGG THIS

The weekly injection of just 100 billionths of a gram of a harmless glyco-protein (a naturally-produced molecule with a sugar component and a protein component) activates the human immune system and cures cancer for good, according to human studies among breast cancer and colon cancer patients, producing complete remissions lasting 4 and 7 years respectively. This glyco-protein cure is totally without side effect but currently goes unused by cancer doctors.
Normal Gc protein (also called vitamin D binding protein), an abundant glyco-protein found in human blood serum, becomes the molecular switch to activate macrophages when it is converted to its active form, called Gc macrophage activating factor (Gc-MAF). Gc protein is normally activated by conversion to Gc-MAF with the help of the B and T cells (bone marrow-made and thymus gland-made white blood cells). But, as researchers explain it themselves, cancer cells secrete an enzyme known as alpha-N-acetylgalactosaminidase (also called Nagalase) that completely blocks conversion of Gc protein to Gc-MAF, preventing tumor-cell killing by the macrophages. This is the way cancer cells escape detection and destruction, by disengaging the human immune system. This also leaves cancer patients prone to infections and many then succumb to pneumonia or other infections.
The once-weekly injection of minute amounts of Gc-MAF, just 100 nanograms (billionths of a gram), activates macrophages and allows the immune system to pursue cancer cells with vigor, sufficient to produce total long-term cures in humans.
Nobuto Yamamoto, director of the Division of Cancer Immunology and Molecular Biology, Socrates Institute for Therapeutic Immunology, Philadelphia, Pennsylvania, says this is "probably the most potent macrophage activating factor ever discovered."

A MACROPHAGE OVERCOMES AND EATS A CANCER CELL
FROM THE UPJOHN COMPANY, THE IMMUNE SYSTEM
Once a sufficient number of activated macrophages are produced, another Gc-MAF injection is not needed for a week because macrophages have a half-life of about six days. After 16-22 weekly doses of Gc-MAF the amount of Nagalase enzyme fell to levels found in healthy people, which serves as evidence tumors have been completely eliminated. The treatment was fool-proof – it worked in 100% of 16 breast cancer patients and there were no recurrent tumors over a period of 4 years, says a report in the January 15 issue of the International Journal of Cancer. [International Journal Cancer. 2008 January15; 122(2):461-7]
In another startling follow-up report by Dr. Yamamoto and colleagues, published in the upcoming July issue of Cancer Immunology Immunotherapy, Gc-MAF therapy totally abolished tumors in 8 colon cancer patients who had already undergone surgery but still exhibited circulating cancer cells (metastases). After 32-50 weekly injections, "all colorectal cancer patients exhibited healthy control levels of the serum Nagalase activity, indicating eradication of metastatic tumor cells," said researchers, an effect that lasted 7 years with no indication of cancer recurrence either by enzyme activity or CT scans, said researchers. [Cancer Immunology, Immunotherapy Volume 57, Number 7 / July, 2008] Published in an early online edition of this journal, this confirming report has received no attention by the new media so far, despite its striking importance.
Gc-MAF treatment for cancer has been agonizingly slow to develop. Dr. Yamamoto first described this immuno-therapy in 1993. [The Journal of Immunology, 1993 151 (5); 2794-2802]
● Untreated mice ○ Mice given macrophage activating factor
In a similar animal experiment published in 2003, researchers in Germany, Japan and the United States collaborated to successfully demonstrate that after they had injected macrophage activating factor (Gc-MAF) into tumor-bearing mice, it totally eradicated tumors (see the above chart). [Neoplasia 2003 January; 5(1): 32–40]
In 1997 Dr. Yamamoto injected Gc-MAF protein into tumor-bearing mice, with the same startling results. A single enzyme injection doubled the survival of these mice and just four enzyme injections increased survival by 6-fold. [Cancer Research 1997 Jun 1; 57(11):2187-92]
In 1996 Dr. Yamamoto reported that all 52 cancer patients he had studied carried elevated blood plasma levels of the immune inactivating alpha-N-acetylgalactosaminidase enzyme (Nagalase), whereas healthy humans had very low levels of this enzyme. [Cancer Research 1996 Jun 15; 56(12):2827-31]
In the early 1990s Dr. Yamamoto first described how the human immune system is disengaged by enzymes secreted from cancer cells, even filing a patent on the proposed therapy. [US Patent 5326749, July 1994; Cancer Research 1996 June 15; 56: 2827-31]
Activated Gc protein has been used in humans at much higher doses without side effect. This Gc macrophage activating factor (Gc-MAF) has been shown to be effective against a variety of cancers including breast, prostate, stomach, liver, lung, uterus, ovary, brain, skin, head/neck cancer and leukemia.
Although Gc-MAF is also called vitamin D binding protein, the activation of macrophages does not require vitamin D.
It cannot be said the Gc-MAF cancer cure has gone unheralded. Reuters News covered this developing story in January. But the news story still did not receive top billing nor did it fully elucidate the importance of the discovery, actually made years ago, that the human body is capable of abolishing cancer once its immune system is properly activated.
Gc-MAF is a naturally made molecule and is not patentable, though its manufacturing process is patent protected. There is no evidence of any current effort to commercialize this therapy or put it into practice. Should such an effective treatment for cancer come into common practice, the income stream from health insurance plans for every oncology office and cancer center in the world would likely be reduced to the point of financial insolvency and hundreds of thousands of jobs would be eliminated.
The National Cancer Institute estimates cancer care in the U.S. costs ~$72 billion annually (2004). Furthermore, about $55 billion of cancer drugs are used annually, none which have not significantly improved survival rates throughout the history of their use. If a typical cancer patient had to undergo 30 Gc-MAF injections at a cost of $150 per injection, that would cost ~$4500, not counting doctor’s office visits and follow-up testing. For comparison, gene-targeted cancer drugs range from $13,000 to $100,000 in cost per year and produce only marginal improvements in survival (weeks to months). [Targeted Oncology 2007 April, 2 (2); 113-19]
Up to this point, the National Cancer Institute is totally silent on this discovery and there is no evidence the cancer care industry plans to quickly mobilize to use this otherwise harmless treatment.
Timothy Hubbell, a biochemist from Cincinnati, first called attention to this discovery and provided consultation on the biochemistry.

Macrophage Activation May Suppress Breast Cancer Metastasis
By David Douglas
NEW YORK FEB 20, 2008 (Reuters Health) – Vitamin D-binding protein-derived macrophage activating factor (Gc-MAF) appears to be an effective immunotherapeutic agent in patients with metastatic breast cancer, according to US and Japanese researchers.
"Serum vitamin D-binding protein – known as Gc protein – is the precursor of the principal macrophage activating factor," lead investigator Dr. Nobuto Yamamoto told Reuters Health.
"Treatment of purified Gc protein with beta-galactosidase and sialidase generates Gc-MAF," he added, "the most potent macrophage activating factor ever discovered, which produces no side effect in humans."
Dr. Yamamoto of the Socrates Institute for Therapeutic Immunology, Philadelphia and colleagues note that in vitro studies show that macrophages treated with Gc-MAF have a highly tumoricidal effect in mammary adenocarcinomas.
To investigate whether the approach can be effective in humans, the researchers studied 16 non-anemic breast cancer patients who were given "a minute amount – 100 nanograms per week – of Gc-MAF," Dr. Yamamoto said.
The researchers found that after 16 to 22 Gc-MAF doses, initially elevated nagalase levels, which reflect the tumor burden, fell to those found in healthy controls. Follow-up over 4 years showed that the level remained low and that there was no tumor recurrence, they report in the January 15th issue of The International Journal of Cancer.
The findings, the team concludes, clearly demonstrate "the importance of focusing cancer immunotherapy on macrophage activation."
International Journal Cancer. 2008 Jan 15; 122(2):461-7.
Immunotherapy of metastatic breast cancer patients with vitamin D-binding protein-derived macrophage activating factor (Gc-MAF).
Yamamoto N, Suyama H, Yamamoto N, Ushijima N.
Division of Cancer Immunology and Molecular Biology, Socrates Institute for Therapeutic Immunology, Philadelphia, PA 19126-3305, USA. nobutoyama@verizon.net
Serum vitamin D3-binding protein (Gc protein) is the precursor for the principal macrophage activating factor (MAF). The MAF precursor activity of serum Gc protein of breast cancer patients was lost or reduced because Gc protein was deglycosylated by serum alpha-N-acetylgalactosaminidase (Nagalase) secreted from cancerous cells. Patient serum Nagalase activity is proportional to tumor burden. The deglycosylated Gc protein cannot be converted to MAF, resulting in no macrophage activation and immunosuppression. Stepwise incubation of purified Gc protein with immobilized beta-galactosidase and sialidase generated probably the most potent macrophage activating factor (termed Gc-MAF) ever discovered, which produces no adverse effect in humans. Macrophages treated in vitro with Gc-MAF (100 pg/ml) are highly tumoricidal to mammary adenocarcinomas. Efficacy of Gc-MAF for treatment of metastatic breast cancer was investigated with 16 nonanemic patients who received weekly administration of Gc-MAF (100 ng). As Gc-MAF therapy progresses, the MAF precursor activity of patient Gc protein increased with a concomitant decrease in serum Nagalase. Because of proportionality of serum Nagalase activity to tumor burden, the time course progress of Gc-MAF therapy was assessed by serum Nagalase activity as a prognostic index. These patients had the initial Nagalase activities ranging from 2.32 to 6.28 nmole/min/mg protein. After about 16-22 administrations (approximately 3.5-5 months) of Gc-MAF, these patients had insignificantly low serum enzyme levels equivalent to healthy control enzyme levels, ranging from 0.38 to 0.63 nmole/min/mg protein, indicating eradication of the tumors. This therapeutic procedure resulted in no recurrence for more than 4 years. Copyright 2007 Wiley-Liss, Inc.
Cancer Immunology, Immunotherapy 2008 July 57 (7): online
Immunotherapy of metastatic colorectal cancer with vitamin D-binding protein-derived macrophage-activating factor, Gc-MAF
Nobuto Yamamoto, Hirofumi Suyama, Hiroaki Nakazato, Nobuyuki Yamamoto and Yoshihiko Koga
Abstract: Serum vitamin D binding protein (Gc protein) is the precursor for the principal macrophage-activating factor (MAF). The MAF precursor activity of serum Gc protein of colorectal cancer patients was lost or reduced because Gc protein is deglycosylated by serum α-N-acetylgalactosaminidase (Nagalase) secreted from cancerous cells. Deglycosylated Gc protein cannot be converted to MAF, leading to immunosuppression. Stepwise treatment of purified Gc protein with immobilized β-galactosidase and sialidase generated the most potent macrophage-activating factor (Gc-MAF) ever discovered, but it produces no side effect in humans. Macrophages treated with Gc-MAF (100 pg/ml) develop an enormous variation of receptors and are highly tumoricidal to a variety of cancers indiscriminately. Administration of 100 nanogram (ng)/human maximally activates systemic macrophages that can kill cancerous cells. Since the half-life of the activated macrophages is approximately 6 days, 100 ng Gc-MAF was administered weekly to eight nonanemic colorectal cancer patients who had previously received tumor-resection but still carried significant amounts of metastatic tumor cells. As Gc-MAF therapy progressed, the MAF precursor activities of all patients increased and conversely their serum Nagalase activities decreased. Since serum Nagalase is proportional to tumor burden, serum Nagalase activity was used as a prognostic index for time course analysis of Gc-MAF therapy. After 32–50 weekly administrations of 100 ng Gc-MAF, all colorectal cancer patients exhibited healthy control levels of the serum Nagalase activity, indicating eradication of metastatic tumor cells. During 7 years after the completion of Gc-MAF therapy, their serum Nagalase activity did not increase, indicating no recurrence of cancer, which was also supported by the annual CT scans of these patients.
May 22, 2008
Bill Sardi [send him mail]is author of the new book: You Don’t Have To Be Afraid Of Cancer Anymore.
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Old 09-12-2008, 11:28 PM   #3
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Hmmm. No one has anything to say about this?
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Old 09-13-2008, 07:36 AM   #4
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Rich - I just sent it off to Caryn's Onc for his response. He's been very open minded so I look forward to his reaction. I'll let you know. Thanks for posting.

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Old 09-13-2008, 04:31 PM   #5
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An interesting thread here:
http://www.imminst.org/forum/Gc-macr...et-t22146.html
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Old 09-14-2008, 12:15 PM   #6
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Conversation with reporter/author:
Contact me ASAP if you can comment on this.
Rich
Nothing to comment on......................... GcMAF not available anywhere, even though healthy people make it and could be donors to cancer patients.

Bill Sardi
Was the study legit? Is this Socrates Institute real? What happend here?



Socrates Institute is real. Harvard doctors have spoken to Yamamoto.

He has dreams of commercialization and wants to get a patent on a fractionated version of GcMAF when the natural form worked completely (100%) without side effect, but of course there is no patent to be had.

B Sardi

All any oncologist need do is get a protocol approved by an institutional review board and inject GcMAF from healthy to cancer patients. Would take months to get approval, probably.

B Sardi


Yamamoto is seriously withholding until he can patent it? If the natural is unpatentable, isn't there a non-profit that could bring this about? There must be money motivated, money possessing folks that want cancer gone.
Rich

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Old 09-14-2008, 01:27 PM   #7
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Nobuto Yamamoto's patent application

Preparation of potent macrophage activating factors derived from cloned vitamin d binding protein and its domain and their therapeutic usage for cancer, hiv-infection and osteopetrosis

USPTO Application #: 20060014143
Title: Preparation of potent macrophage activating factors derived from cloned vitamin d binding protein and its domain and their therapeutic usage for cancer, hiv-infection and osteopetrosis
Abstract: Vitamin D-binding protein (Gc protein) and its small domain (approximately ⅕ of the Gc peptide also known as domain III) were cloned via a baculovirus vector. The cloned Gc protein and the cloned domain (Cd) peptide were treated with immobilized β-galactosidase and sialidase to yield macrophage activating factors, GcMAFc and CdMAF, respectively. These cloned macrophage activating factors and GcMAF are to be used for therapy of cancer, HIV-infection and osteopetrosis, and may also be used as adjuvants for [COLOR=blue ! important][COLOR=blue ! important]immunization[/COLOR][/COLOR] and vaccination.
(end of abstract)

Agent: Caesar, Rivise, Bernstein, Cohen & Pokotilow, Ltd. - Philadelphia, PA, US
Inventor: Nobuto Yamamoto
USPTO Applicaton #: 20060014143 - Class: 435005000 (USPTO)

Full Patent Description
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Old 09-25-2008, 11:47 AM   #8
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I actually reached Dr. Yamamoto by phone. He said the process of making the GcMAF is very expensive and difficult. He is trying to raise funding for this but claims the onco world and funding sources are not receptive. Talked with me for a surprisingly long time and seemed genuine in his concern. Mentioned that traditional chemo could be somewhat bettered by having a longer rest period (3-4 weeks) to encourage a slight version of his approach. Is this just an eccentric guy fudging the results or will be seeing his ideas come to light at some point? It all confuses me.
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Old 09-25-2008, 11:59 AM   #9
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Hard to say...I was just reading about Dr. Judah Folkman, the man who pioneered the understanding of angiogenesis and it's role in cancer growth. He was ridiculed for 25 years but never gave up on his research...which eventually led to the acceptance of his theory and subsequent targeting of these pathways with Avastin and other drugs...

All I can say is, it takes way too long and too many valid ideas probably end up on the side of the road waiting for acceptance and funding.

By the way, tho, the book I was reading this in was actually about how you can improve the "terrain" in your body to improve your own immune response and attack cancer's weaknesses. Primarily through diet and lifestyle changes. One point of the Judah Folkman story was that the agents that disrupt/prevent antiogenesis are ALSO available in many of the foods we eat...and you don't have to wait for the Avastins to come out.

Which comes full circle back to some of the earlier discussion on your topic - how could we mimic these effects through dietary interventions? That might be an interesting conversation to have with Dr. Yamamoto!
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June 2002 extensive hi grade DCIS (pre-cancer-stage 0, clean sentinal node) Mastectomy/implant - no chemo, rads. "cured?"
9/2004 Diag: Stage IV extensive liver mets (!) ER/PR- Her2+++
10/04-3/05 Weekly Taxol/Carboplatin/Herceptin , complete response!
04/05 - 4/07 Herception every 3 wks, Continue NED
04/07 - recurrence to liver - 2 spots, starting tykerb/avastin trial
06/07 8/07 10/07 Scans show stable, continue on Tykerb/Avastin
01/08 Progression in liver
02/08 Begin (TDM1) trial
08/08 NED! It's Working! Continue on TDM1
02/09 Continue NED
02/10 Continue NED. 5/10 9/10 Scans NED 10/10 Scans NED
12/10 Scans not clear....4/11 Scans suggest progression 6/11 progression confirmed in liver
07/11 - 11/11 Herceptin/Xeloda -not working:(
12/11 Begin MM302 Phase I trial - bust:(
03/12 3rd times the charm? AKT trial

5/12 Scan shows reduction! 7/12 More reduction!!!!
8/12 Whoops...progression...trying for Perjeta/Herceptin (plus some more nasty chemo!)
9/12 Start Perjeta/Herceptin, chemo on hold due to infection/wound in leg, added on cycle 2 &3
11/12 Poops! progression in liver, Stop Perjeta/Taxo/Herc
11/12 Navelbine/Herce[ptin - try for a 3 cycles, no go.
2/13 Gemzar/Carbo/Herceptin - no go.
3/13 TACE procedure

Last edited by chrisy; 09-25-2008 at 12:05 PM..
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