Oncoimmunology. 2013 Aug 1; 2(8): e25769.
Published online 2013 Jul 29. doi: 10.4161/onci.25769
PMCID: PMC3812199
GC protein-derived macrophage-activating factor decreases α-N-acetylgalactosaminidase levels in advanced cancer patients
Lynda Thyer,
1
Emma Ward,
1
Rodney Smith,
1
Jacopo JV Branca,
2
Gabriele Morucci,
2
Massimo Gulisano,
2
David Noakes,
3
Robert Eslinger,
4
and Stefania Pacini
2
,*
This article has been cited by other articles in PMC.
Abstract
α-N-acetylgalactosaminidase
(nagalase) accumulates in the serum of cancer patients and its activity
correlates with tumor burden, aggressiveness and clinical disease
progression. The administration of GC protein-derived
macrophage-activating factor (GcMAF) to cancer patients with elevated
levels of nagalase has been associated with a decrease of serum nagalase
activity and with significant clinical benefits. Here, we report the
results of the administration of GcMAF to a heterogeneous cohort of
patients with histologically diverse, advanced neoplasms, generally
considered as “incurable” diseases. In most cases, GcMAF therapy was
initiated at late stages of tumor progression. As this is an open-label,
non-controlled, retrospective analysis, caution must be employed when
establishing cause-effect relationships between the administration GcMAF
and disease outcome. However, the response to GcMAF was generally
robust and some trends emerged. All patients (n = 20) presented with
elevated serum nagalase activity, well above normal values. All patients
but one showed a significant decrease of serum nagalase activity upon
weekly GcMAF injections. Decreased nagalase activity was associated with
improved clinical conditions and no adverse side effects were reported.
The observations reported here confirm and extend previous results and
pave the way to further studies aimed at assessing the precise role and
indications for GcMAF-based anticancer immunotherapy.
Keywords: cancer, complementary medicine, immunotherapy, macrophages, Vitamin D
Introduction
α-N-acetylgalactosaminidase
(nagalase) is known to accumulate in the serum of cancer patients,
where it mediates the deglycosylation of group-specific component (GC),
best known as vitamin D-binding protein (VDBP), which is the precursor
of GC protein-derived macrophage-activating factor (GcMAF).
Deglycosylated VDBP cannot be converted into GcMAF1 and decreased GcMAF levels reportedly promote immunodeficiency in individuals bearing advanced neoplasms.2
The increase in nagalase activity observed in cancer patients is mostly
due to the fact that malignant cells release enzymatically active
nagalase.3
Thus, serum nagalase activity reflects not only tumor burden and
aggressiveness, but also the clinical progression of the disease.4-7
Nowadays, the assessment of serum nagalase activity is proposed as a
reliable means to determine the clinical severity of multiple neoplasms.3
In serum, nagalase acts as an endo- (but not as an exo-) enzyme, being unable to deglycosylate an N-acetylgalactosamine (GalNAc) residue of GcMAF.5 Thus, circulating nagalase cannot degrade exogenous GcMAF.5-7
This observation suggested that patients with elevated nagalase
activity may benefit from the exogenous provision of GcMAF. Alongside,
GcMAF was observed to exert multiple anticancer effects in vivo and in
vitro, both in experimental and in spontaneous tumor models. Given the
impact of GcMAF on macrophages and their central role anticancer immune
responses, GcMAF is widely considered as an immunotherapeutic agent.7
However, in addition to stimulating tumor-infiltrating macrophages,8 GcMAF not only directly inhibits the proliferation of various human cancer cells in vitro,9,10 but also reverts the malignant phenotype of human breast cancer cells.10
Moreover, GcMAF reportedly inhibits angiogenesis, thus depriving
neoplastic lesions of the oxygen and nutrient supplies that are needed
for tumor progression and metastasis.10-13
Recently, it has been proposed that the antineoplastic effects of GcMAF
are mediated by the vitamin D receptor (VDR), and it was demonstrated
that GcMAF stimulates an intracellular signaling pathway impinging on
cyclic AMP. This signal transduction cascade could actually be
responsible for death of malignant cells exposed to GcMAF.12
Taken together, these in vitro and in vivo findings lend a rationale to
the observation that GcMAF exert dramatic anticancer effects in (at
least a fraction of) patients with advanced cancer.5-7
Of note, in the aforementioned studies, the anticancer effects of GcMAF
were evaluated by measuring serum nagalase activity as a marker of
tumor burden and progression.2,3,14
The
biological effects of GcMAF have been documented in a variety of
experimental systems and make the subject of more than 50 peer-reviewed
papers published during the past 20 y.15
Because of the solid scientific rationale underlying the compassionate
use of GcMAF in advanced cancer patients, hundreds of physicians in all
parts of the world have adopted this approach for a variety of
indications in which it could prove useful. Here, we present a series of
clinical cases exemplifying the results that have been obtained with
the administration of GcMAF to patients with diverse types of advanced
cancers, with a particular focus on the effects of GcMAF on serum
nagalase activity. We are well aware that these cases, because of their
heterogeneity and reduced number, can be considered anecdotal. However, a
very recent study on the evaluation of clinical practice strongly
encourages the re-evaluation of individual cases such as those presented
here.16
Thus, while some studies present large and impressive statistics
obtained from large clinical cohorts, others may report a limited number
of noteworthy cases, as we do here. According to this novel,
authoritative, epistemological approach, “all of these stories become
evidence of what works in medicine.”16
Therefore, we believe that the clinical cases reported below point to
beneficial effects for the administration of GcMAF to advanced cancer
patients, prompting further studies to formally address this
possibility.
Results
The
mean pre-GcMAF treatment serum nagalase activity documented in our
patient cohort was 2.84 ± 0.26 nM/min/mg, with a range of 1.00–5.60
nM/min/mg (Table 1).
At the time of second testing (average interval = 112 d), the mean
serum nagalase activity in the course of GcMAF treatment was 2.01 ± 0.22
nM/min/mg, with a range of 1.00–3.20 nM/min/mg. The difference between
these values was statistically significant (p < 0.05). Of note, no
patient of this cohort was initially observed to be within the
laboratory reference range for serum nagalase activity (0.90–0.92
nM/min/mg). At the time of final testing (average interval = 263 d), the
mean serum nagalase activity of the patient cohort was 1.59 ± 0.17
nM/min/mg, with a range of 0.60–2.80 nM/min/mg. The difference between
this value and the serum nagalase activity recorded before the
initiation of GcMAF treatment was also statistically significant (p <
0.01).
Narrative description of some notable clinical cases from The Netherlands
The
following reports were collected and communicated by Dr. Steven Hofman
(CMC, Capelle aan den Ijssel; The Netherlands) and refer to the years
2011–2012. In addition to GcMAF, most patients were prescribed
supplementation of vitamins D and A. Additional supplements are
indicated when assumed. Most of the patients did not assume conventional
anticancer chemotherapy along with GcMAF. However, several patients had
been subjected to conventional anticancer therapies in the previous
years, as indicated in individual reports. When patients assumed
conventional therapeutics, such as hormones, in the course of GcMAF
administration (e.g., patient #8), this is indicated in the individual
report. When not indicated otherwise, patients received 100 ng GcMAF
weekly, as a single intramuscular injection, in line the commonly
accepted recommendations.5-7 Original reports are in italics. Each case is referred to with progressive numbers, as in Table 1.
In Figure 1,
the decrease of serum nagalase activity in the patient cohort is
plotted in function of the consecutive testing. Of note, since this is a
retrospective analysis and not a clinical trial, nagalase
determinations were not performed at the same time point in each
individual patient. The overall shape of the graph, however, is very
similar if not completely superimposable to that of other graphs of the
same type that have previously been reported.5-7,17
Figure 1.
Time course of GcMAF treatment in 7 cancer patients with serum nagalase
activity as a prognostic index. Data correspond to the patients
described in the section “Narrative description of some notable clinical
cases from The Netherlands.” ...
2. Male,
born 1950. Carcinoma of the urine-bladder since 2009, previously
treated with chemo-solutions locally. Nagalase level at presentation on
July 4, 2011: 3.10. February 10, 2012: 2.30. May 25, 2012: 1.80. October
26, 2012: 1.40. Treatment with GcMAF and acupuncture, later GcMAF only
(later intravenous route). Bladder considered clean by urologist in
summer 2012. GcMAF-treatment continued. In this case, the
consistent decrease in serum nagalase activity was associated with a
significant clinical improvement. The drop in nagalase activity was
evident at the first post-treatment testing, about 7 mo after the
initiation of GcMAF treatment, and persisted until the last available
determination, i.e., about 15 mo thereafter. The difference in serum
nagalase activity as recorded before at last determination and before
the initiation of GcMAF therapy was -1.70 nM/min/mg.
3. Female,
born 1944. Bladder carcinoma treated since 2011 by urologist with
curettage and BCG. Nagalase level at presentation on May 9, 2011: 4.10.
October 24, 2011: 2.30. April 3, 2012: 1.40. September 10, 2012: 1.00.
December 4, 2012: 0.75. During the nagalase testing period the Patient
was advised to inject intramuscular GcMAF weekly, but the Patient was
not consistent. The bladder was considered in good condition on several
occasions this period by the treating urologist. Also in this case,
a consistent decrease in serum nagalase activity was associated with a
significant clinical improvement. Such a decrease in nagalase activity
was evident at the first post-treatment testing, about 5 mo after the
initiation of GcMAF treatment, and persisted until the last available
determination, i.e., about 19 mo thereafter. The difference in serum
nagalase activity as recorded before at last determination and before
the initiation of GcMAF therapy was -3.35 nM/min/mg. The last available
value of serum nagalase activity, 0.75 nM/min/mg, was within the normal
range.
8. Male, born 1937. Prostate carcinoma found
by PSA in 2009, no specific complaints. Treated by hormone-injections,
which gave complaints. Before and in the same year colon carcinoma was
found, and operated after irradiation and chemotherapy (no untreated
tumor/metastases probable). Nagalase level at presentation on April 6,
2011: 2.00. August 29, 2011: 1.20. January 5, 2012: 0.81. July 5, 2012:
0.67. December 6, 2012: 0.75. Treatment with acupuncture and GcMAF;
after some time, the hormone treatment was discontinued and complaints,
also non-specific, improved a lot. Stays on low-frequency surveillance.
Again, serum nagalase activity returned to normal values (0.75
nM/min/mg) after about 20 mo of GcMAF treatment. A decrease in nagalase
activity, however, was evident already at the first test, i.e., 4 mo
after the initiation of GcMAF treatment. According to the literature,7 the normalization of serum nagalase levels in prostate cancer patients may represent an index of tumor eradication.
9. Male,
born 1948. Prostate carcinoma in 2008; prostate extirpated in 2009 with
good prognosis. However aspecific reportts fatigue and pain stayed.
GcMAF treatment was started, together with a few acupuncture treatments.
Nagalase level at presentation on October 21, 2011: 1.90. February 2,
2012: 1.70. October 19, 2012: 1.20. Complaints decreased gradually and
the injections were performed intravenously later on. The treatment
continues.
10. Female, born 1947. Carcinoma of
left breast (found on survey), operated with sentinel nodes in 2010,
chemotherapy 4 of 6 series, no specific complaints left. Still some
malaise, fatigue and sleep-disorder. Nagalase level at presentation on
August 9, 2011: 1.70. January 16, 2012: 1.00. March 12, 2012: 0.72.
December 11, 2012: 0.60. GcMAF-treatment (predominantly intravenous
route) combined with acupuncture. GcMAF discontinued in April 2012.
Aspecific complaints diminished. Patient still seen every few months.
A significant decrease in serum nagalase activity could be observed
after 5 mo of GcMAF treatment. Such a decrease persisted even after the
interruption of GcMAF, and serum nagalase activity was normalized about
16 mo after the initiation of therapy. According to the literature,5 the normalization of serum nagalase activity in breast carcinoma patients may represent an index of tumor eradication.
11. Female,
born 1950. Carcinoma of left breast, specific complaints, metastases
probable. After local operation, irradiation of thorax, combined with
chemotherapy, Herceptin-therapy. Partly complaints in association with
treatments. Nagalase level at presentation on May 11, 2011: 5.60.
October 6, 2011: 2.90. February 21, 2012: 1.80. October 18, 2012: 1.10.
Treated with intramuscular, later intravenous GcMAF, and a few
acupuncture-treatments. No further complaints (subsided in 3–6 weeks),
still in intravenous GcMAF regimen. A significant decrease in serum
nagalase activity could be observed approximately 5 mo after the
initiation of therapy. Approximately after 17 mo of GcMAF treatment,
serum nagalase levels approached normal values.
16. Male,
born 1941. Larynx-carcinoma found and treated with curettage and
irradiation in 2010. Hemorrhagic-recto-colitis in anamnesis, few
complaints after 2005. Bladder carcinoma found in 2011, treated by local
curettage and several cycles of BCG-instillations. Complaints related
to tumor growth and treatments, no chemotherapy. Treatment consisted of
acupuncture and GcMAF intramuscular, and later intravenous injections on
a weekly basis. Nagalase level at presentation on May 16, 2011: 4.70.
October 4, 2011: 2.00. February 10, 2012: 1.20. June 15, 2012: 1.00.
October 23, 2012: 0.88. December 20, 2012: 0.90. During the
immunotherapy with GcMAF there were interesting developments. Insisting
on bladder extirpation by the urologists, coped with one change of
urologist, two second opinions by a specialized cancer clinic and later
by an urologist of the operation team scheduled. From the Patients side
there were several favorable adjustments in lifestyle, like
discontinuation of smoking and adopting a daily intake of cod-liver-oil
and salvia-leaf (his own initiative). In the face of the urologists
opinion I decided to give the GcMAF twice weekly over a period of six
weeks. The last opinion of the treating urologist was to postpone a more
final decision to February, due to a much better impression of the
bladder mucosa beginning in January 2013. There is optimism in the three
named actors in the current situation. In this case, a significant
decrease of in serum nagalase activation following the administration
of GcMAF was associated with significant clinical benefits, consistent
with previous reports.7
Narrative description of some notable clinical cases from the United States of America
The
following reports were communicated by RE and refer to the years
2012–2013. In most patients, the weekly administration of 100 ng GcMAF
i.m. was initiated in August 2012, and the first assessment of serum
nagalase activity was performed immediately before the initiation of
treatment. None of the patients assumed conventional anticancer
chemotherapy during along with GcMAF. Here, we report only those cases
for which as least two nagalase determinations were available.
1. Male, age 64. Bladder carcinoma. Nagalase level at first testing in October 2012: 2.90. In January 2013: 2.60. Improved.
In this case, a decrease in serum nagalase activity could be documented
in about 3 mo of GcMAF treatment and was associated with clinical
improvement.
4. Female, age 60. Ovarian carcinoma.
Nagalase level at first testing in June 2012: 3.30. November 2012: 2.80.
CA-125 tumor marker in December 2012: 15.7. In February 2013: 19.1
Improved. The weekly administration of GcMAF resulted in a
significant decrease of serum nagalase activity in about 3 mo. Such a
decrease was associated with clinical benefits. These changes, however,
were not (as yet) associated with a decrease in the circulating levels
of cancer antigen 125 (CA-125), another tumor marker.
7. Male, age 67. Prostate carcinoma. Nagalase level at first testing in August 2012: 3.40. In December 2012: 2.80. Improved.
In this case, clinical benefits were associated with a significant
decrease in serum nagalase activity in about 4 mo from the initiation of
GcMAF therapy. These results are consistent with the findings reported
above as well as with previously described cases.7
12. Male,
age 63. Squamous cell carcinoma of the tongue. Nagalase level at first
testing in July 2012: 3.00. In September 2012: 1.50. In December 2012:
1.00. Improved. Again, clinical improvement was associated with a
significant decrease in serum nagalase activity, which approached the
normal range in approximately 5 mo. To the best of our knowledge, this
is the first case of a patient affected by squamous cell carcinoma of
the tongue receiving GcMAF. Also patient n. Thirteen (Table 1)
was treated with GcMAF for a squamous cell carcinoma of the tongue and
showed a decrease in serum nagalase activity in about 3 mo.
14. Male, age 54. Colorectal cancer. Nagalase level at first testing in July 2012: 3.90. In October 2012: 2.00. Discontinued.
In this case, a significant decrease of serum nagalase activity could
be documented approximately 3 mo after the initiation of GcMAF therapy.
We are not aware of the reasons that led to treatment discontinuation.
15. Female,
age 58. Squamous cell carcinoma of the head and neck. Nagalase level at
first testing in June 2012: 2.90. In July 2012: 2.70. In February 2013:
2.00. Improved. In this case, a minimal decrease in serum nagalase
activity as observed after 1 mo of GcMAF administration was associated
with clinical benefits.
17. Female, age 35.
Squamous cell carcinoma. Nagalase level at first testing in June 2012:
1.50. In September 2012: 1.10. Discontinued. In this case, a
decrease of serum nagalase activity was observed after 3 mo of GcMAF
therapy. We are not aware of the reasons that led to treatment
discontinuation.
18. Female, age 69. Follicular
lymphoma. Nagalase level at first testing in June 2012: 1.00. In August
2012: 1.30. In January 2013: 1.20. Improved. In this case, no association between serum nagalase activity, GcMAF treatment and clinical conditions could be revealed.
19. Female, age 66. Lymphoma. Nagalase level at first testing in August 2012: 2.20. In November 2012: 1.90. Improved.
In this case, a clinical improvement was associated with a significant
decrease in serum nagalase activity in about 3 mo after the initiation
of GcMAF treatment.
Discussion
GcMAF has been shown to inhibit multiple aspects of neoplastic transformation in vitro, in a variety of tumor models.5-10
The clinical cases reported here are heterogeneous and refer to
patients with different types of neoplasms and at different stages of
malignant progression. These cases include cancer patients in whom the
effects of GcMAF had not been described before, such as subjects bearing
various types of head and neck carcinoma (including tumors of the
larynx and tongue), lymphoma, oligodendrocytoma and ovarian carcinoma.
In some instances, patients were simultaneously affected by multiple
types of tumors, as reported in the narrative description. In many
cases, patients received GcMAF along with other complementary
treatments, such as acupuncture or administration of nutritional
supplements. In all cases, GcMAF therapy was initiated at late stages of
tumor progression, as conventional therapies were obviously preferred
at less advanced stages. Thus, most of the cases described here fall
under the category of compassionate treatment. In fact, most of these
patients had undergone conventional anticancer therapy in the previous
years and had referred to GcMAF treatment when conventional chemo- or
radiotherapy had proven ineffective or intolerable, as described in the
individual reports. Since this is an open-label, non-controlled,
retrospective analysis, caution must be employed in drawing a
cause-effect relationship between treatment and clinical outcome.
However, the response to GcMAF was often relatively robust and certain
trends stand out.
Trends from Dutch cases
1. All patients presented with serum nagalase activity well above the normal value, that is about 0.95 nM/min/mg.
2. All patients showed a significant decrease in serum nagalase activity following GcMAF injections.
3.
In all cases, serum nagalase activity was reduced at the second
assessment, and such a decrease persisted in the following
determinations.
4. In 4/7 cases, serum nagalase activity returned to normal levels by the last assessment.
Trends from American cases
1.
All patients, but one, presented with serum nagalase activity well
above the normal value. Patient #18, indeed, presented with a serum
nagalase activity that was very close to normal.
2. In
most patients, a significant decrease in serum nagalase activity was
observed upon the administration of GcMAF. In patient #18, such a
decrease was not associated with clinical benefits, even though her
serum nagalase activity was always on the low side. This lack of a
strict inverse relationship between serum nagalase activity and clinical
responses has been recently observed in a study describing the effects
of GcMAF in autistic children. Most of these patients showed indeed a
decrease in serum nagalase activity as well as a significant improvement
of symptoms, but the two phenomena were not strictly correlated with
each other.18
A
significant point that emerges from the analysis of the cases described
above is the apparent absence of GcMAF-related side effects. This
point, which has previously been documented in autistic children,18
is of great importance when GcMAF is considered for the compassionate
treatment of patients with advanced or incurable diseases. As a matter
of fact, in many countries, the complete absence of side effects is a
prerequisite for the compassionate administration of substances that
have not yet been approved by local sanitary authorities.
Obviously,
these preliminary observations require a prolonged follow-up period to
determine the best indications for the compassionate administration of
GcMAF. As of today, GcMAF has been used (always as a compassionate
therapy) with encouraging results in patients affected by virtually all
types of cancers and at all stages of disease progression. However, it
is tempting to hypothesize that patients bearing specific types and/or
stages of malignancy might obtain consistent clinical benefits from the
administration of GcMAF. Also the genetic background of patients, in
particular in terms of VDR polymorphisms, might influence the
individual response to GcMAF. In fact, we have recently demonstrated
that the degree of response of human monocytes to GcMAF is associated
with individual VDR genotypes.13
It can therefore be hypothesized that the antineoplastic effects of
GcMAF may also be influenced by such polymorphisms. Moreover, it should
be kept in mind that the prognosis of patients affected by all types of
cancers is dependent upon their nutritional and inflammatory status,
which can be monitored by the Prognostic Inflammatory and Nutritional
Index (PINI).19
The PINI score might therefore become part of the laboratory
assessments performed in the course of GcMAF therapy, and - together
with the assessment of serum nagalase activity testing and VDR
polymorphisms - it may assist physicians in monitoring the response of
individual patient to GcMAF and adjusting doses and schedules in the
course of treatment, if required. Studies investigating the impact of GC
polymorphisms on the response of cancer patients to GcMAF therapy as
well as the contribution of distinct GC variants to the relative amounts
of “non-inducible,” inactive GcMAF species20 will also be instrumental in determining the most correct approach to GcMAF administration.
The results reported here are consistent with previous results5-7 as well as with a recent publication by Inui et al.,21
who described three clinical cases successfully treated with
combinatorial therapeutic regimens including subcutaneous or
intramuscular injections of GcMAF-containing human serum. At variance
with this latter study, the results presented here were obtained with
highly purified GcMAF, ruling out the effects of other serum proteins
that might have acted as confounding factors.
In
conclusion, the clinical cases presented here reinforce the hypothesis
that GcMAF could become part of anticancer immunotherapeutic regimens.
Materials and Methods
GcMAF production
Physicians
obtained GcMAF from Immuno Biotech Ltd (Guernsey, UK). GcMAF was highly
purified according to previously described procedures.7
Briefly, VDBP was isolated from purified human serum obtained from the
American Red Cross, using either 25-hydroxyvitamin D3-sepharose high
affinity chromatography or actin-agarose affinity chromatography. Bound
material was eluted and further processed by incubation with three
immobilized enzymes. The resulting GcMAF was filter sterilized. Protein
content and concentration of the GcMAF solution were assayed using
standard Bradford protein assay methods.22
At the end of the production process, GcMAF was checked for sterility
in-house as well as externally, by independent laboratories. The safety
and biological activity of GcMAF were tested on human monocytes,13 human breast cancer cells,10 and chick embryo chorionallantoic membranes.12
Data collection
A
retrospective chart review for the analysis of nagalase testing was
accomplished on the initial cohort of patients seen by the clinicians
(RE and Dr. Steven Hofman, CMC, Capelle aan den Ijssel; The
Netherlands). All records were reviewed by physicians for confirmation
of serum nagalase activity values, diagnoses, time intervals between
testing, GcMAF dosing and clinical responses. The diagnosis of cancer
was confirmed by other treating physicians.
GcMAF administration
The
administration of GcMAF to individual patients was performed
exclusively by their physicians (RE and Dr. Steven Hofman, CMC, Capelle
aan den Ijssel; The Netherlands), according to the national rules and
regulations. Original clinical records are conserved by the physicians,
in their respective locations, as indicated. In the Results section,
clinical cases are reported as close as possible to the originals notes
of physicians, with minimal grammar and spelling corrections. Since each
physicians used described the condition of individual patients in a
different fashion, some heterogeneity in these notes has to be expected.
The notes are purposely presented as they had been written so that each
reader can draw her/his conclusions.
Serum nagalase activity determinations
Serum
nagalase testing was performed at ELN Laboratories (Bunnik, The
Netherlands) following the procedure published by Yamamoto et al.14
In particular, serum nagalase activity was determined by using an
endpoint enzymatic assay based on a chromogenic substrate. ELN
Laboratories established a reference range of 0.32–0.95 nM/min/mg of
substrate based on serum samples collected from healthy volunteers, a
range slightly higher than that previously reported, which was of
0.35–0.65 nM/min/mg.14
Further studies on elevated numbers of subjects will establish the most
appropriate reference range. Irrespective of this issue, since all
determinations were performed in the same laboratory, a relative
decrease of in serum nagalase activity following GcMAF administration
was used as an index of therapeutic efficacy.
Statistical methods
Statistical
comparisons between the serum nagalase activity observed before and
after (at two distinct time points) the administration of GcMAF were
performed by Student’s t-tests.
Acknowledgments
The
Authors wish to thank Dr. Steven Hofman, CMC, Capelle aan den Ijssel,
The Netherlands, for providing the data concerning the patients he
treated as well as for critical review of this study.
Disclosure of Potential Conflicts of Interest
DN
is the CEO of Immuno Biotech Ltd (the company isolating and purifying
the GcMAF protein). However, DN had no knowledge of the therapies being
used nor of the names of any patients whose data were being analyzed.
Neither he, nor any employee of Immuno Biotech Ltd, had any knowledge of
the nagalase or other test results or the patient names used in this
study.
Glossary
Abbreviations:
BCG | bacillus Calmette-Guérin |
CA-125 | cancer antigen 125 |
GalNAc | N-acetylgalactosamine |
GcMAF | GC protein-derived macrophage-activating factor |
PINI | prognostic inflammatory and nutritional index |
PSA | prostate-specific antigen |
VDBP | vitamin D-binding protein |
VDR | vitamin D receptor |
Footnotes
Previously published online: www.landesbioscience.com/journals/oncoimmunology/article/25769
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