<i>Retracted</i>: Immunotherapy of metastatic breast cancer patients with vitamin D‐binding protein‐derived macrophage activating factor (GcMAF)

Yamamoto, Nobuto; Suyama, Hirofumi; Yamamoto, Nobuyuki; Ushijima, Naofumi

doi:10.1002/ijc.23107

Cited by 54 publications

(78 citation statements)

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“…VDBP is involved in calcium homeostasis, immunity (21,22), and antiangiogenic (23) as well as antiproliferation processes (24). The protein is primarily synthesized in the liver and secreted into the plasma, where it binds to vitamin D and known to be taken up by human mammary cells via endocytosis (25).…”

Section: Discussionmentioning

confidence: 99%

“…With regards to immunity, VDBP is involved in macrophage activation by having its branched trisaccharide complex hydrolyzed by b-glactosidase on B cells and salidase from T cells forming the macrophage activating factor (GcMAF). In patients with metastatic breast cancer it was found that administration of VDBP in the form of GcMAF decreased Nagalase activity, an indicator of macrophage activation that can lead to cancer cell death (21).…”

Section: Discussionmentioning

confidence: 99%

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Proteomic Changes Induced by Effective Chemopreventive Ratios of n-3:n-6 Fatty Acids and Tamoxifen against MNU-Induced Mammary Cancer in the Rat

Skibinski

Thompson

Das

et al. 2013

Cancer Prevention Research

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We used a proteomic approach to gain insights into the mechanisms of protection at the protein level by a high n-3:n-6 ratio in the absence and presence of Tamoxifen. Four groups were treated with 1-methyl-1-nitrosourea (MNU) and fed the following diets with varied n-3:n-6 ratios; group 1 ¼ 1:1; groups 2 and 3 ¼ 10:1 and 25:1, respectively; group 4: (25:1) plus Tamoxifen (1 mg/kg diet). The plasma from six rats/group was pooled and analyzed with the isobaric tags for relative and absolute quantitation method; 148 proteins were identified with 95% confidence by ProteinPilot 4.0. In plasma of rats fed 10:1, 25:1 n-3:n-6, and 25:1 plus Tamoxifen, the number of proteins that met our criteria (P 0.05, error factor 2) were 10, 14, and 19 proteins, respectively. Selected proteins were further validated by Western blotting. Compared to 1:1, both 10:1 and 25:1 diets upregulated vitamin D binding protein, gelsolin, and 14-3-3 sigma, reported to have tumor suppressive effects, whereas alpha-1B-glycoprotein, which has been reported to be elevated in the serum of breast cancer patients was decreased. Compared to 25:1, the 25:1 plus Tamoxifen diet downregulated apolipoprotein E, haptoglobin, and inter-a-inhibitor H4 heavy chain. Ingenuity pathway analysis determined that the trends of specific proteins were related to lipid metabolism in the 25:1 n-3:n-6 group, whereas the 25:1 n-3:n-6 plus Tamoxifen group included proteins involved in cancer and inflammation. Our results show that several proteins were altered in a manner consistent with chemoprevention. Such proteins may serve as biomarkers to monitor efficacy of n-3 and Tamoxifen in future clinical chemoprevention trials. Cancer Prev Res; 6(9); 979-88. Ó2013 AACR.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Proteomic Changes Induced by Effective Chemopreventive Ratios of n-3:n-6 Fatty Acids and Tamoxifen against MNU-Induced Mammary Cancer in the Rat

Skibinski

Thompson

Das

et al. 2013

Cancer Prevention Research

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“…[1][2][3] Molecularly, GcMAF is thought to be DBP with a single terminal O-linked GalNAc sugar residue. [4][5][6][7] In its native molecular state, DBP is a mixture of posttranslationally unmodified (except for disulfide bonds) and O-glycosylated species, the glycosidic degree and nature of which depends on DBP genotype.…”

Section: Introductionmentioning

confidence: 99%

Glycosylation status of vitamin D binding protein in cancer patients

2009

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On the basis of the results of activity studies, previous reports have suggested that vitamin D binding protein (DBP) is significantly or even completely deglycosylated in cancer patients, eliminating the molecular precursor of the immunologically important Gc macrophage activating factor (GcMAF), a glycosidase-derived product of DBP. The purpose of this investigation was to directly determine the relative degree of O-linked trisaccharide glycosylation of serumderived DBP in human breast, colorectal, pancreatic, and prostate cancer patients. Results obtained by electrospray ionization-based mass spectrometric immunoassay showed that there was no significant depletion of DBP trisaccharide glycosylation in the 56 cancer patients examined relative to healthy controls. These results suggest that alternative hypotheses regarding the molecular and/or structural origins of GcMAF must be considered to explain the relative inability of cancer patient serum to activate macrophages.

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“…Although GcMAF therapy has been found to show curative effects on a variety of cancers (10-13,37,38), Yamamoto et al stated that the efficacy of GcMAF therapy for a variety of cancer types depends on the degree of cell membrane abnormality (12,13). Undifferentiated tumor cells are killed more efficiently than differentiated tumor cells.…”

Section: Discussionmentioning

confidence: 99%

“…Highly activated macrophages have been reported to have a tumoricidal potential (6)(7)(8)(9). Pilot studies have reported the efficacy of GcMAF-based immunotherapy of metastatic cancer in animal and humans (10)(11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

Inhibitory effect of vitamin D-binding protein-derived macrophage activating factor on DMBA-induced hamster cheek pouch carcinogenesis and its derived carcinoma cell line

et al. 2011

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Abstract. This study investigated the inhibitory effect of vitamin D-binding protein-derived macrophage-activating factor (GcMAF) on carcinogenesis and tumor growth, using a 9,10-dimethyl-1,2-benzanthracene (DMBA)-induced hamster cheek pouch carcinogenesis model, as well as the cytocidal effect of activated macrophages against HCPC-1, a cell line established from DMBA-induced cheek pouch carcinoma. DMBA application induced squamous cell carcinoma in all 15 hamsters of the control group at approximately 10 weeks, and all 15 hamsters died of tumor burden within 20 weeks. By contrast, 2 out of the 14 hamsters with GcMAF administration did not develop tumors and the remaining 12 hamsters showed a significant delay of tumor development for approximately 3.5 weeks. The growth of tumors formed was significantly suppressed and none of the hamsters died within the 20 weeks during which they were observed. When GcMAF administration was stopped at the 13th week of the experiment in 4 out of the 14 hamsters in the GcMAF-treated group, tumor growth was promoted, but none of the mice died within the 20-week period. On the other hand, when GcMAF administration was commenced after the 13th week in 5 out of the 15 hamsters in the control group, tumor growth was slightly suppressed and all 15 hamsters died of tumor burden. However, the mean survival time was significantly extended. GcMAF treatment activated peritoneal macrophages in vitro and in vivo, and these activated macrophages exhibited a marked cytocidal effect on HCPC-1 cells. Furthermore, the cytocidal effect of activated macrophages was enhanced by the addition of tumor-bearing hamster serum. These findings indicated that GcMAF possesses an inhibitory effect on tumor development and growth in a DMBA-induced hamster cheek pouch carcinogenesis model.

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Retracted: Immunotherapy of metastatic breast cancer patients with vitamin D‐binding protein‐derived macrophage activating factor (GcMAF)

Cited by 54 publications

References 50 publications

Proteomic Changes Induced by Effective Chemopreventive Ratios of n-3:n-6 Fatty Acids and Tamoxifen against MNU-Induced Mammary Cancer in the Rat

Proteomic Changes Induced by Effective Chemopreventive Ratios of n-3:n-6 Fatty Acids and Tamoxifen against MNU-Induced Mammary Cancer in the Rat

Glycosylation status of vitamin D binding protein in cancer patients

Inhibitory effect of vitamin D-binding protein-derived macrophage activating factor on DMBA-induced hamster cheek pouch carcinogenesis and its derived carcinoma cell line

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