Scientific Researches On:
Grifola Frondosa (Maitake Mushroom)
USA National Center for Biotechnology Information
1:
J Vet Intern Med.
2007 Nov-Dec;21(6):1409-12.
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Mushroom-derived maitake
PETfraction as single agent for
the treatment of lymphoma in dogs.
Griessmayr PC,
Gauthier M,
Barber LG,
Cotter SM.
Harrington Oncology Program,
Cummings School of Veterinary
Medicine at Tufts University,
North Grafton, MA 01536, USA.
BACKGROUND: Maitake PETfraction is
a standardized essence extracted
from the mushroom Maitake (Grifola
frondosa) that has antitumor
activity in tumor-bearing mice. In
addition, PETfraction induces
apoptosis in human prostate and
bladder cancer cells and
suppresses the proliferation in
vitro of several canine tumor cell
lines, such as lymphoma (Cl-1),
mammary gland (CF33), and
connective tissue (CF21).
HYPOTHESIS: Maitake PETfraction is
effective as a single agent in
dogs with lymphoma. ANIMALS:
Fifteen dogs with confirmed
intermediate or high-grade
lymphoma were enrolled into this
prospective, noncontrolled,
clinical trial. Inclusion criteria
were an expected survival time of
at least 2 weeks and no major
organ dysfunction. METHODS:
Maitake PETfraction was
administered at a dose of 3
drops/kg/day divided into 2 doses
given 1 hour before feeding. Dogs
were evaluated by physical
examination with tumor
measurement, body weight, CBC, and
chemistry profile before treatment
and after 2, 4, 8, and 12 weeks.
At each visit, owners completed a
questionnaire addressing overall
quality of life, appetite, and any
adverse effects noted. RESULTS: A
decrease in lymph node size of
greater than 50% (objective
response) was not seen in any of
the dogs. Thirteen dogs developed
progressive disease before the 4th
week. The median treatment
duration was 27 days (range,
9-228). PETfraction was well
accepted, and minimal adverse
effects were observed. Two dogs
developed hyphema. It was not
known if this was related to
progressive lymphoma or was an
adverse effect of treatment.
CONCLUSIONS: No objective
responses were observed to
administration of Maitake
PETfraction, and the drug was well
tolerated in these dogs.
Publication Types:
PMID: 18196755 [PubMed - indexed
for MEDLINE]
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Effect of various natural
products on growth of bladder
cancer cells: two promising
mushroom extracts.
Konno S.
New York Medical College;
Department of Urology; Munger
Pavilion 4th Floor; Valhalla, NY
10595, USA. sensuke_konno@nymc.edu
Despite the availability of
several therapeutic options, a
safer and more effective modality
is urgently needed for treatment
of bladder cancer. Specific
immunotherapy is effective, but
severe side effects limit its
clinical use and underscore the
need for unconventional therapies
using less toxic substances. Many
natural substances are touted for
their medicinal aspects and side
effect profiles, and some of these
have been well characterized for
their biological and medicinal
properties. Accordingly, the
effects on bladder cancer cells in
vitro were investigated. Eight
commercially available natural
products were tested for possible
effects on the growth of human
bladder cancer T24 cells. This
study demonstrated that two
mushroom extracts, GD- and
PL-fractions, induced a
significant (>90 percent) growth
reduction in 72 hours, whereas the
remaining six products had no
effect. Interestingly, non-toxic
concentrations of the GD- or
PL-fractions, when combined with a
non-toxic concentration of vitamin
C, became highly cytotoxic,
resulting in >90-percent cell
death. Thus, vitamin C appears to
act synergistically with these
fractions to potentiate their
bioactivity (cytotoxicity). No
other products tested demonstrated
such a synergistic potentiation
with vitamin C. The present study
indicates that GD- and
PL-fractions appear to have the
most potent cytotoxic effect on
human bladder cancer T24 cells. It
is thus plausible that these
substances could be used, solely
or combined with conventional
modalities, for the treatment of
superficial bladder cancer.
Publication Types:
PMID: 17397268 [PubMed - indexed
for MEDLINE]
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A method for the isolation of
blocked N-terminal peptides.
Coussot G,
Hawke DH,
Mularz A,
Koomen JM,
Kobayashi R.
Department of Molecular Pathology,
University of Texas, M. D.
Anderson Cancer Center, Houston,
TX 77230, USA.
Publication Types:
PMID: 17188638 [PubMed - indexed
for MEDLINE]
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Induction of apoptosis in
SGC-7901 cells by
polysaccharide-peptide GFPS1b from
the cultured mycelia of Grifola
frondosa GF9801.
Cui FJ,
Li Y,
Xu YY,
Liu ZQ,
Huang DM,
Zhang ZC,
Tao WY.
Institute of Bioengineering,
School of Food and Biotechnology,
Jiangsu University, Xuefu Road,
Zhenjiang, Jiangsu 212013, PR
China. fengjiecui@sytu.edu.cn
The biological function of
GFPPS1b, a novel
polysaccharide-peptide isolated
from cultured mycelia of Grifola
frondosa GF9801, was well
investigated. GFPS1b has
anti-tumor activity and can
significantly inhibit the
proliferation of SGC-7901 cells,
whereas slightly influences the
growth of human normal liver cell
line L-02. When treated with
GFPS1b, SGC-7901 cells showed
typical apoptotic morphological
features such as the loss of
villus and appearance of apoptotic
bodies on the cell surface, volume
reduction, and chromatin
condensation, by scanning electron
microscopy (SEM) and fluorescent
microscopy (Hoechst 33342). The
results of flow cytometry analysis
and annexin V-PI assay showed that
the SGC-7901 cell cycle was
arrested in the G(2)/M phase, the
subdiploid peak of DNA
characteristic of apoptotic was
also observed, and the apoptosis
ratio was about 15.08%. DNA
isolated from SGC-7901 cells
cultured with GFPS1b showed a
typical DNA 'ladders' of apoptosis
in agarose gel electrophoresis.
Further investigation results
showed that the apoptotic
machinery of SGC-7901 induced by
GFPS1b was associated with drop in
mitochondrial trans-membrane
potential, upregulation of Bax,
downregulation of Bcl-2, and
activation of caspase-3. Our
finding suggests that GFPS1b could
suppress SGC-7901 cell growth and
reduce cell survival via arresting
cell cycle and inducing apoptosis
of tumor cells.
Publication Types:
PMID: 17150327 [PubMed - indexed
for MEDLINE]
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Enhancement of umbilical cord
blood cell hematopoiesis by
maitake beta-glucan is mediated by
granulocyte colony-stimulating
factor production.
Lin H,
Cheung SW,
Nesin M,
Cassileth BR,
Cunningham-Rundles S.
Integrative Medicine Service,
Memorial Sloan-Kettering Cancer
Center, New York, NY, USA.
Maitake beta-glucan (MBG) is an
extract from the fruit body of the
Grifola frondosa mushroom that is
being widely used to treat cancer
in Asia. We have previously
reported that MBG enhances mouse
bone marrow cell (BMC)
hematopoiesis in vitro and
protects BMC from doxorubicin (DOX)
toxicity. In the current study, we
investigated the ability of MBG to
enhance hematopoiesis and to
reduce the toxic effects of DOX on
fresh human umbilical cord blood
(CB) cells. MBG treatment
significantly enhanced the colony
formation unit (CFU) response of
granulocytes-macrophages (CFU-GM
response) over the whole dose
range of 12.5 to 100 microg/ml (P
< 0.05). The addition of MBG to
DOX-treated CB cells significantly
protected granulocyte-macrophage
colony formation from the toxicity
of DOX, which otherwise produced
strong hematopoietic repression.
MBG also partially replaced
recombinant human granulocyte
colony-stimulating factor (rhG-CSF),
as shown by a significant
augmentation of the CFU-GM
response in the absence of rhG-CSF.
We found that MBG induces
granulocyte colony-stimulating
factor (G-CSF) production in CB
CD33+ monocytes, as detected by
intracellular cytokine flow
cytometric assessment. In
contrast, we found that adult
peripheral blood monocytes did not
produce a significant G-CSF
response to MBG, whereas both
adult and CB monocytes produced G-CSF
in response to lipopolysaccharide.
These studies provide the first
evidence that MBG induces
hematopoietic stem cell
proliferation and differentiation
of CFU-GM in umbilical CB cells
and acts directly to induce G-CSF.
Publication Types:
PMID: 17093103 [PubMed - indexed
for MEDLINE]
PMCID:
PMC1797710
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o-Orsellinaldehyde from the
submerged culture of the edible
mushroom Grifola frondosa exhibits
selective cytotoxic effect against
Hep 3B cells through apoptosis.
Lin JT,
Liu WH.
Institute of Microbiology and
Biochemistry, National Taiwan
University, No.1, Sec. 4,
Roosevelt Road, Taipei, Taiwan.
The tumoricidal activity of a
bioactive metabolite produced by
submerged culture in a 2.1-L
airlift fermentor of Grifola
frondosa NTUS was investigated.
After 14 days of cultivation,
ethyl acetate extracts from the
supernatant of culture broth (EES)
were analyzed by cell viability
assay. The IC50 of EES for
cytotoxicity against human
carcinoma cells (Hep 3B, Hep G2,
HeLa, CL1-1) and normal human lung
fibroblast MRC-5 was 78.4, 52.7,
77.6, 71.0, and 233.3 microg/mL,
respectively. EES was further
fractionated and a main cytotoxic
compound, HE-5-5, was obtained.
The IC50 of HE-5-5 based on the
cell viability of Hep 3B and MRC-5
cells was 3.6 and 33.1 microg/mL,
respectively. Thus, HE-5-5 showed
a selective cytotoxic effect
against Hep 3B cells and MRC-5.
According to the UV, MS, and NMR
data, HE-5-5 was identified as o-orsellinaldehyde.
A DNA fragmentation assay together
with the presence of a significant
sub-G1 peak by flow cytometry
suggested that o-orsellinaldehyde
might mediate its cytotoxicity
through apoptosis.
PMID: 17002422 [PubMed - indexed
for MEDLINE]
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Preparation of a chemically
sulfated polysaccharide derived
from Grifola frondosa and its
potential biological activities.
Nie X,
Shi B,
Ding Y,
Tao W.
College of Biological and
Environmental Engineering,
Zhejiang University of Technology,
Hangzhou, PR China.
niexiaohua2000@126.com
This report describes the
preparation, characterization and
potential biological activities of
a chemically sulfated
polysaccharide (S-GAP-P), which
was derived from water-insoluble
polysaccharide of Grifola frondosa
mycelia. S-GAP-P was determined to
be a glucan sulfate with the
average molecular weight of 28 kDa
and the sulfur content of 16.4%.
The antitumor and immunomodulating
activities of the sulfated
derivative were estimated in vitro
and in vivo. S-GAP-P inhibited the
proliferation of SGC-7901 cells
and induced apoptosis, in a
dose-dependent manner. And the
results from in vivo experiments
demonstrated that S-GAP-P
significantly inhibited the tumor
growth and enhanced the peritoneal
macrophages phagocytosis in
S180-bearing mice. It is
noteworthy that S-GAP-P could
accelerate the antitumor activity
of CTX and improve the
immunocompetence damaged by CTX,
suggesting the combination might
increase cytotoxic efficacy and
decrease toxicity of some
chemotherapeutic agents in cancer
treatment.
Publication Types:
PMID: 16822541 [PubMed - indexed
for MEDLINE]
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Maitake D-Fraction enhances
antitumor effects and reduces
immunosuppression by mitomycin-C
in tumor-bearing mice.
Kodama N,
Murata Y,
Asakawa A,
Inui A,
Hayashi M,
Sakai N,
Nanba H.
Department of Microbial Chemistry,
Kobe Pharmaceutical University,
Kobe, Japan. n-kodama@kobepharma-u.ac.jp
OBJECTIVE: D-Fraction, a
polysaccharide extracted from
maitake mushrooms (Grifola
frondosa), has been reported to
exhibit an antitumor effect
through activation of
immunocompetent cells, including
macrophages and T cells, with
modulation of the balance between
T-helper 1 and 2 cells. We
examined whether D-Fraction could
decrease the effective dosage of
the chemotherapeutic agent,
mitomycin-C (MMC), necessary to
control carcinoma in mice. METHODS
AND RESULTS: We determined that
0.25 mg.kg-1.d-1 was the optimal
dosage of MMC because consecutive
administration for 17 d resulted
in antitumor effects and a
survival ratio of 100% in mice
bearing mammary cancer cells
(MM-46). Although the dosage of
MMC was lower than the effective
level, spleen weight and total
number of nuclear cells in the
mouse spleen decreased, indicating
that MMC showed immunosuppressive
activity. In contrast, the
combination of D-Fraction and MMC
recovered the decreases in the
dose response induced by MMC and
inhibited tumor cell growth more
than MMC alone. These effects were
achieved through increased
immunocompetent cell
proliferation. We evaluated the
expression of CD28 on splenic CD8+
T cells and the amount of
interleukin-12 produced by whole
spleen cells including macrophages
after administering D-Fraction.
The results showed enhancement of
the T-helper 1 dominant response.
CONCLUSION: These results suggest
that D-Fraction can decrease the
effective dosage in tumor-bearing
mice by increasing the
proliferation, differentiation,
and activation of immunocompetent
cells and thus provide a potential
clinical benefit for patients with
cancer.
PMID: 15850970 [PubMed - indexed
for MEDLINE]
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Selective induction of
apoptosis in murine skin carcinoma
cells (CH72) by an ethanol extract
of Lentinula edodes.
Gu YH,
Belury MA.
Bastyr University, 14500 Juanita
Drive NE, WA 98028, USA.
The effects of ethanol extracts
from four species of mushroom
fruiting bodies, mushroom spores
and mushroom cultured broth, were
assessed for modulation of cell
proliferation and apoptosis in
murine skin carcinoma cells (CH72)
and non-tumorigenic epidermal
cells (C50). While extracts from
mycelia of Grifola frondosa,
Ganoderma lucidum, Hericium
erinaceus, or from spores of G.
lucidum exerted little, if any,
effect on proliferation, the
ethanol-soluble extract of
Lentinula edodes (L. edodes)
significantly decreased cell
proliferation of CH72 cells. There
were no changes in the
proliferative response of the non-tumorigenic
keratinocyte cell line, C50, to
any of the mushroom extracts
tested. To analyze cell
proliferation and apoptosis,
fluorescent DNA-microscopy with
ethidium bromide and acridine
orange staining of cells revealed
L. edodes reduced cell
proliferation and induced
apoptosis in time- and
dose-dependent manners in
carcinoma cells but had no effect
in non-tumorigenic cells (C50).
Cell cycle analysis demonstrated
that L. edodes extract induced a
transient G(1) arrest, with no
changes observed in the non-tumorigenic
cells (C50).
Publication Types:
PMID: 15737684 [PubMed - indexed
for MEDLINE]
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Potential growth inhibitory
effect of maitake D-fraction on
canine cancer cells.
Konno S.
Department of Urology, New York
Medical College, Munger Pavilion
4th Floor, Valhalla, NY, 10595,
USA.
The postulated anticancer effect
of D-fraction, the bioactive
extract of maitake mushroom, on
three types (CF33, CF21, and CL-1)
of canine cancer cells was
evaluated. The effect of
D-fraction on several human cancer
cells was also investigated. The
effect of other beta-glucan
products was likewise examined.
D-fraction was highly effective on
the canine cancer cells, either
potently inhibiting cell growth or
directly killing cells. Similar
effects were also demonstrated in
certain human cancer cells.
However, other beta-glucan
products relevant to D-fraction
had no such effects on canine
cancer cells. Therefore,
D-fraction is a potent natural
agent that could be useful in
treating canine cancers as well as
other veterinary cancers.
PMID: 15719326 [PubMed - indexed
for MEDLINE]
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Enhancement of cytotoxicity of
NK cells by D-Fraction, a
polysaccharide from Grifola
frondosa.
Kodama N,
Asakawa A,
Inui A,
Masuda Y,
Nanba H.
Department of Microbial Chemistry,
Kobe Pharmaceutical University,
4-19-1 Motoyama-kitamachi,
Higashinada-ku, Kobe 658-8558,
Japan. n-kodama@kobepharma-u.ac.jp
In innate immunity, activated
natural killer (NK) cells attack
and damage pathogens such as
bacteria and virus without
restriction by the MHC antigen. NK
cells activated by IL-12 have been
reported to recognize and kill
tumor cells in perforin-mediated
apoptosis. We have reported that
D-Fraction, a polysaccharide
extracted from the maitake
mushroom (Grifola frondosa),
activates macrophages, dendritic
cells, and T cells and inhibits
the growth of tumor cells.
However, the effects of D-Fraction
on NK cell function in the innate
immune response are not well
known. In the present study, we
administered D-Fraction to MM-46
mammary tumor-bearing C3H/HeJ mice
intraperitoneally for 3
consecutive days and investigated
its effects on the activation and
cytotoxicity of NK cells.
D-Fraction significantly enhanced
the cytotoxicity against NK-sensitive
YAC-1 cells and the expression of
CD223 on NK cells. D-Fraction also
increased the expression of CD86
on macrophages. In addition, the
levels of IL-12 in the culture
supernatant of whole spleen cells
and in serum increased, compared
with the control corresponding to
an increase in expression of IL-12
receptor betaI on NK cells. These
results suggest that D-Fraction
enhances the cytotoxicity of NK
cells through the production of
IL-12 by macrophages activated by
D-Fraction.
PMID: 15706424 [PubMed - indexed
for MEDLINE]
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Administration of a
polysaccharide from Grifola
frondosa stimulates immune
function of normal mice.
Kodama N,
Murata Y,
Nanba H.
Department of Microbial Chemistry,
Kobe Pharmaceutical University,
19-1 Motoyama-kitamachi 4-chome,
Higashinada-ku, Kobe 658-8558,
Japan. n-kodama@kobepharma-u.ac.jp
We have reported that D-Fraction,
a polysaccharide extracted from
the edible maitake mushroom (Grifola
frondosa), activates
immunocompetent cells, thereby
eliciting antitumor activity. To
extend the application of
D-Fraction as a nutritional
supplement for healthy people as
well as treatment for those with
cancer, we investigated the
effects of D-Fraction on the
immune system in normal C3H/HeJ
mice. Splenocytes from mice
administered D-Fraction
intraperitoneally for 17
consecutive days were cultured,
and the culture supernatants were
analyzed for nitric oxide (NO) and
interleukin (IL)-12 production by
antigen-presenting cells (APCs),
including macrophages and
dendritic cells, and also for the
T helper (Th)-1 cytokine
interferon (IFN)-gamma and the
Th-2 cytokines IL-4 and IL-10. The
level of IL-10 as well as those of
NO and IFN-gamma were increased by
D-Fraction as compared with the
control, in which the serum
immunoglobulin E level was
increased. The results suggest
that D-Fraction induced a Th-2
dominant response through the
activation of macrophages,
resulting in the enhancement of
humoral immunity rather than
cell-mediated immunity.
Furthermore, an increase in the
percentage ratio of CD69 and CD89
expression on major
histocompatibility complex II(+)
cells revealed activation of APCs
4 h after D-Fraction
administration. These results
indicate that D-Fraction enhances
both the innate and adaptive arms
of the immune response in normal
mice. Therefore, its
administration may enhance host
defense against foreign pathogens
and protect healthy individuals
from infectious diseases.
PMID: 15298759 [PubMed - indexed
for MEDLINE]
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Effect of Maitake (Grifola
frondosa) D-Fraction on the
activation of NK cells in cancer
patients.
Kodama N,
Komuta K,
Nanba H.
Department of Microbial Chemistry,
Kobe Pharmaceutical University,
Kobe, Japan. n-kodama@kobepharma-u.ac.jp
Maitake D-Fraction, extracted from
maitake mushroom, has been
reported to exert its antitumor
effect in tumor-bearing mice by
enhancing the immune system
through activation of macrophages,
T cells, and natural killer (NK)
cells. In a previous study, the
combination of immunotherapy with
the maitake D-Fraction and
chemotherapy suggested that the
D-Fraction may have the potential
to decrease the size of lung,
liver, and breast tumors in cancer
patients. In the present study, we
administered maitake D-Fraction to
cancer patients without anticancer
drugs, and at the same time NK
cell activity was monitored to
investigate whether the activity
is closely related with disease
progression. The numbers of CD4(+)
and CD8(+) cells in the peripheral
blood were measured in 10
patients, and NK cell activity was
assessed using K-562 cells as
target cells. Serum soluble
interleukin-2 receptor (sIL-2R)
levels in three patients and the
expression of tumor markers in
four patients were determined by
enzyme-linked immunosorbent assay.
The slight changes observed in the
CD4(+) and CD8(+) cell numbers
were independent of disease
severity or stage as well as serum
sIL-2R levels. In contrast,
maitake D-Fraction hindered
metastatic progress, lessened the
expression of tumor markers, and
increased NK cell activity in all
patients examined. Thus maitake
D-Fraction appears to repress
cancer progression and primarily
exerts its effect through
stimulation of NK activity. In
addition, we conclude that
measurement of NK cell activity
may be a useful clinical parameter
in monitoring disease progression
during and following immunotherapy
with maitake D-Fraction.
PMID: 14977447 [PubMed - indexed
for MEDLINE]
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Maitake beta-glucan MD-fraction
enhances bone marrow colony
formation and reduces doxorubicin
toxicity in vitro.
Lin H,
She YH,
Cassileth BR,
Sirotnak F,
Cunningham Rundles S.
Integrative Medicine Service,
Memorial Sloan-Kettering Cancer
Center, New York, NY, USA.
Previous studies have indicated
that MD-fraction (MDF), in which
the active component is beta
1,6-glucan with beta 1,3-branches,
has anti-tumor activity as an oral
agent and acts as an immune
adjuvant. Since some other beta
glucans appear to promote
mobilization of hematopoietic stem
cells, the effects of a beta
glucan extract from the Maitake
mushroom "MD-fraction" on
hematopoietic stem cells were
examined in a colony forming
assay. Here we report for the
first time that MDF has a dose
response effect on mouse bone
marrow cells (BMC) hematopoiesis
in vitro. Using the Colony Forming
Unit (CFU) assay to detect
formation of
granulocyte-macrophage (CFU-GM)
colonies, and the XTT
cytotoxicitiy assay to measure BMC
viability, the data showed that
the addition of MDF significantly
enhanced the development of CFU-GM
in a dose range of 50-100 microg/ml
(p<0.004). The mechanism of action
included significant increase of
nonadherent BMC viability, which
was observed at MDF doses of
12.5-100 microg/ml (p<0.005). In
the presence of Doxorubicin (DOX),
MDF promoted BMC viability and
protected CFU-GM from DOX induced
toxicity. In addition, MDF
treatment promoted the recovery of
CFU-GM colony formation after BMC
were pretreated with DOX. These
studies provided the first
evidence that MDF acts directly in
a dose dependent manner on
hematopoietic BMC and enhances BMC
growth and differentiation into
colony forming cells.
Publication Types:
PMID: 14975363 [PubMed - indexed
for MEDLINE]
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[Anti-tumor effect of
polysaccharide from Grifola
frondosa and its influence on
immunological function]
[Article in Chinese]
Li X,
Rong J,
Wu M,
Zeng X.
Department of Food Science and
Technology, Huazhong Agricultural
University, Wuhan 430070.
When the polysaccharide from
Grifola frondosa (PGF) was taken
orally by S180 bearing mice at the
dosage of 50-150 mg/kg.d for 9 d,
the inhibitory rate to S180 was
27.97%-38.46%. The PGF can also
enhance thymus index, the ability
of splenic lymphocyte
proliferation and formation of
antibody in splenic cells, and
promote the production of IgM
hemolysin significantly in S-180
bearing mice.
Publication Types:
PMID: 12858772 [PubMed - indexed
for MEDLINE]
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Relationship between dendritic
cells and the D-fraction-induced
Th-1 dominant response in BALB/c
tumor-bearing mice.
Harada N,
Kodama N,
Nanba H.
Department of Microbial Chemistry,
Kobe Pharmaceutical University,
4-19-1, Motoyama-kitamachi,
Higashinada-ku, 658-8558, Kobe,
Japan.
Dendritic cells (DCs) are known to
not only induce the activation of
T cells, but are also associated
with the differentiation of T
cells. The D-fraction, a beta-glucan
extracted from maitake (Grifola
frondosa) which expresses
anti-tumor effects by establishing
a helper (Th)-1 dominance in BALB/c
mice, enhanced IL-12p70 production
by DCs, when the ratio of
CD8alpha(+) DCs to CD8alpha(-) DCs
increased. In addition,
examination of the tumor rejection
effect of D-fraction-stimulated
DCs loaded with tumor antigen
revealed that tumor growth is
inhibited completely by activating
CD4(+) T cells and CD8(+) T cells.
PMID: 12668282 [PubMed - indexed
for MEDLINE]
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A polysaccharide, extract from
Grifola frondosa, induces Th-1
dominant responses in
carcinoma-bearing BALB/c mice.
Kodama N,
Harada N,
Nanba H.
Department of Microbial Chemistry,
Kobe Pharmaceutical University,
Japan. n-kodama@kobepharma-u.ac.jp
A polysaccharide, designated as
the D-fraction, extracted from
maitake (Grifola frondosa), was
reported to have anti-tumor
effects by activating macrophages
and T cells in C3H/HeN mice in
which a Th-1 dominant response was
established. In this study using
BALB/c mice in which a Th-2
response is genetically dominant,
D-fraction reduced the expression
of Th-2 cytokine interleukin
(IL)-4 but markedly increased the
expression of Th-1 cytokine
interferon (IFN)-gamma in CD4(+) T
cells and also increased IL-12p70
production as well as IFN-gamma
production by antigen-presenting
cells (APCs), suggesting that
D-fraction promotes the
differentiation into Th-1 cells of
CD4(+) T cells through enhancement
of IL-12p70 production by APCs.
PMID: 12501013 [PubMed - indexed
for MEDLINE]
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Effects of D-Fraction, a
polysaccharide from Grifola
frondosa on tumor growth involve
activation of NK cells.
Kodama N,
Komuta K,
Sakai N,
Nanba H.
Department of Microbial Chemistry,
Kobe Pharmaceutical University,
Japan. n-kokama@kobepharma-u.ac.jp
Natural killer (NK) cells are
directly cytotoxic for tumor cells
and play a primary role in
regulating immune responses. We
monitored levels of NK cell
cytotoxic activity in cancer
patients receiving D-Fraction
extracted from maitake mushrooms (Grifola
frondosa). Elevated levels of
cytotoxic activity were maintained
for one year. To elucidate the
mechanisms underlying long-term
activation of NK cells during
treatment with D-Fraction, we
examined tumor volume and levels
of IFN-gamma and TNF-alpha in
MM46-bearing C3H/HeN mice to which
D-Fraction was administered for 19
d. D-Fraction markedly suppressed
tumor growth, corresponding with
increases in TNF-alpha and IFN-gamma
released from spleen cells and a
significant increase in TNF-alpha
expressed in NK cells. This
suggests that the D-Fraction
activates NK cells even on the
20th day after treatment.
Furthermore, D-Fraction increased
macrophage-derived interleukin
(IL)-12, which serves to activate
NK cells. These results suggest
that NK cells are not only
responsible for the early effects
of D-Fraction on tumor growth, but
also for the long-term
tumor-suppressive effects of
D-Fraction through increased IL-12
released from macrophages.
PMID: 12499658 [PubMed - indexed
for MEDLINE]
-
-
Comment on:
Several apparent errors
surfaced on reading the article in
the June 2002 issue of Alternative
Medicine Review by Kodama et al.
entitled "Can maitake MD-fraction
aid cancer patients"?
Black W.
Publication Types:
PMID: 12495370 [PubMed - indexed
for MEDLINE]
-
-
Chemosensitization of
carmustine with maitake beta-glucan
on androgen-independent prostatic
cancer cells: involvement of
glyoxalase I.
Finkelstein MP,
Aynehchi S,
Samadi AA,
Drinis S,
Choudhury MS,
Tazaki H,
Konno S.
Department of Urology, New York
Medical College, Valhalla, NY
10595, USA.
OBJECTIVE: To improve the poor
efficacy (< 10%) of chemotherapy
for patients with
hormone-refractory prostate
cancer, we investigated a possible
cytotoxic effect of carmustine/beta-glucan
combination on prostatic cancer
PC-3 cells, focusing on a
glutathione-dependent detoxifying
enzyme, glyoxalase I (Gly-I).
METHODS: Carmustine (BCNU) is an
anticancer agent and a putative
inhibitor of Gly-I, while beta-glucan
is a unique, nontoxic
polysaccharide extracted from
maitake mushrooms. The cytotoxic
effects of BCNU or other
anticancer agents with beta-glucan
on PC-3 cells were assessed by
cell-viability testing and Gly-I
activity was measured using the
spectrophotometric method.
RESULTS: BCNU, 5-fluorouracil
(5-FU), and methotrexate (MTX)
were capable of inducing
approximately a 50% reduction in
cell viability at 72 hours, while
etoposide, cisplatin, and
mitomycin C were all ineffective.
Only the combination of BCNU (50
micro ;mol) and beta-glucan (60
micro g/mL) exhibited an enhanced
cytotoxicity with an approximate
90% cell viability reduction, but
little improvement was seen with
any combinations of 5-FU, MTX, or
beta-glucon. Gly-I assays revealed
that such a profound
(approximately 90%) cell death was
accompanied by an approximate 80%
reduction in Gly-I activity by 6
hours. CONCLUSION: This study
demonstrates a sensitized
cytotoxic effect of BCNU with
beta-glucan in PC-3 cells, which
was associated with a drastic
(approximately 80%) inactivation
of Gly-I. Therefore, the BCNU/beta-glucan
combination may help to improve
current treatment efficacy by
targeting Gly-I, which appears to
be critically involved in prostate
cancer viability.
Publication Types:
PMID: 12470438 [PubMed - indexed
for MEDLINE]
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