Coriolus
Versicolor
1:
Gan To Kagaku Ryoho 2000 Oct;27(11):1737-41 |
|
[Two patients with liver
metastasis from gastric cancer who responded remarkably
to combined therapy of 5'-DFUR and PSK].
[Article in Japanese]
Kitamura M, Umekita N, Inoue S, Miyamoto Y, Maeshiro
T, Saiura A, Tanaka S, Kawahara Y, Arai K, Iwasaki Y,
Ohashi M, Takahashi T
Dept. of Surgery, Tokyo Metropolitan Bokutoh Hospital.
[Medline record in process]
Two patients with liver metastasis from gastric cancer
who responded remarkably to a combined therapy of 5'-DFUR
and PSK are reported. The first patient had liver metastases
8 months postoperatively. Her AFP level was 513 ng/ml
and CEA was 30 ng/ml. After the combined therapy, all
liver metastases showed a calcified change. Tumor markers
of AFP and CEA decreased remarkably to the normal level
within 3 weeks after the therapy. The patient had no
relapse as of December 1999. The second patient with
liver metastases was treated using the same combined
therapy for 14 days preoperatively. The size of liver
metastases had decreased remarkably by the time of the
operation. A small metastasis of S8 (0.5 x 0.5 cm) was
resected. No other liver metastasis was detected by
intraoperative ultrasonography. The patient had no relapse
as of February 2000. It is reported that PSK produces
several cytokines which induce thymidine phosphorylase
expression. The present report suggests that the upregulation
of PyNPase might enhance the antitumor effect of 5'-DFUR.
PMID: 11057326, UI: 20511090
1:
Oncol Rep 2000 Nov-Dec;7(6):1343-7 |
|
Long-term survival after
immunochemotherapy for juvenile colon cancer with peritoneal
dissemination. A case report.
Mukai M, Tokunaga N, Yasuda S, Mukohyama S, Kameya
T, Ishikawa K, Iwase H, Suzuki T, Ishida H, Sadahiro
S, Makuuchi H
Tokai University School of Medicine, Department of Surgery,
Bohseidai, Isehara, Kanagawa 259-1193, Japan.
[Medline record in process]
A 20 year-old man was hospitalized with an abdominal
mass and abdominal distension. Investigations resulted
in a diagnosis of ileus caused by advanced colon cancer
with peritoneal dissemination to the pouch of Douglas.
Palliative surgery was performed to relieve bowel obstruction
and debulk the tumor. Histopathological examination
showed that the tumor was a mucinous adenocarcinoma
invading the serosa without lymph node metastasis. Ascites
collected during the operation was diagnosed as class
V. Administration of PSK (3.0 g/day) and UFT (600 mg/day)
as adjuvant immunochemotherapy was started postoperatively
to achieve tumor dormancy. He has been followed as an
outpatient for 2.5 years with no ascites or abdominal
symptoms.
PMID: 11032941, UI: 20491469
1:
Cancer Biother Radiopharm 1997 Oct;12(5):341-4 |
|
Direct tumor growth suppressive
effect of melanoidin extracted from immunomodulator-PSK.
Kamei H, Hashimoto Y, Koide T, Kojima T, Hasegawa
M, Umeda T
Department of Surgery, Aichi-Gakuin University Hospital,
Nagoya, Japan. kamei@dpc.aichi-gakuin.ac.jp
Melanoidin, which belongs to the melanin group of molecules,
was extracted from the polysaccharide biological response
modifier PSK. Melanoidin was cultured together with
HCT-15 cells derived from human colon cancer and with
AGS cells derived from human gastric carcinoma. After
four days of culture, cell count was compared with that
of the control cells. Significant suppression was observed,
that is, 50% suppression was shown at concentrations
of melanoidin between 200 and 100 micrograms/ml. A histogram
generated by flow cytometry showed elevation of the
tetraploid peak and of that between diploid and tetraploid
peaks, suggesting blockage of S phase and G2 to M phase
of the cell cycle. Thus, melanoidins contained in the
immunomodulator PSK revealed to have a direct tumor
cell growth inhibitory effect.
PMID: 10851484, UI: 20310033
1:
Cancer Biother Radiopharm 1998 Aug;13(4):275-90 |
|
Susceptibility of natural
killer (NK) cells to reactive oxygen species (ROS) and
their restoration by the mimics of superoxide dismutase
(SOD).
Nakamura K, Matsunaga K
Department of Biochemistry, Kitasato University School
of Medicine, Kanagawa, Japan.
Natural killer (NK) cells are susceptible to reactive
oxygen species (ROS), and lose the activity by the effects
of ROS. Cancer bearing hosts usually suffer from oxidative
stress (OS), and the NK-activity decreases to a significantly
lower level than normal controls. Superoxide dismutase
(SOD)-mimicking substances, such as protein-bound polysaccharide
of Coriolus versicolor (Fr) QUEL (PSK) and iron-chelating
chlorine e6-Na (FeCNa), can restore the NK-activity
of cancer bearing hosts, when collaborating with catalase.
Incorporation of 3H-thymidine by ROS-treated NK-cells
is not affected, indicating that these cells are still
active in the nucleic acid metabolism. Intraperitoneal
administration of anti-Asialo GM1 antibody extinguished
the NK-activity. NK-cells affected by ROS lost the adherence
to target cancer cells in both in vitro and in vivo.
ROS may change the surface charge of NK-cells to anionic,
resulting in an inability of adhesion to target cancer
cells which usually show the negative surface charge.
PMID: 10850363, UI: 20308909
1:
Int J Clin Lab Res 1999;29(4):135-40 |
|
Protein-bound polysaccharide
(PSK) induces cytotoxic activity in the NKL human natural
killer cell line.
Pedrinaci S, Algarra I, Garrido F
Departamento de Analisis Clinicos, Hospital Universitario
Virgen de las Nieves, Granada, Spain.
We studied the effect of protein-bound polysaccharide
PSK on the activation of the human natural killer cell
line NKL. We observed an increased natural killer cytotoxic
activity against different tumor cells (K562, Daudi,
and U937) when a standard 2- to 3-h 51chromium release
assay was performed. The results parallel those obtained
after treatment of the NKL cell line with interleukin-2.
The highest cytotoxic activity was reached at a concentration
of 100 microg/ml of PSK. This natural killer activation
was inhibited when the PSK dose was 1,000 microg/ml.
None of the cell surface markers that were analyzed
by fluorescence-activated cell sorting showed variations
after PSK or interleukin-2 treatment of NKL cells. These
markers included CD2, CD11b, CD11c, CD18, CD16, CD54,
CD56, CD98, CD25, CD122, HLA class I, HLA class II,
CD94, ILT2, p58.1, p70, and NKp46. One of these markers
(NKp46) is a major triggering receptor reported to be
involved in the natural cytotoxicity of fresh or cultured
human natural killer cells. In our study, another triggering
receptor must be implicated in PSK-induced natural killer
lysis. Our data suggest that PSK is an important biological
response modifier of natural killer cells in vitro and
may prove to be useful for the study of human natural
killer cell biology.
PMID: 10784373, UI: 20244959
1:
Altern Med Rev 2000 Feb;5(1):4-27 |
|
The use of mushroom glucans
and proteoglycans in cancer treatment.
Kidd PM
Immunoceuticals can be considered as substances having
immunotherapeutic efficacy when taken orally. More than
50 mushroom species have yielded potential immunoceuticals
that exhibit anticancer activity in vitro or in animal
models and of these, six have been investigated in human
cancers. All are non-toxic and very well tolerated.
Lentinan and schizophyllan have little oral activity.
Active Hexose Correlated Compound (AHCC) is poorly defined
but has shown early clinical promise. Maitake D-Fraction
has limited proof of clinical efficacy to date, but
controlled research is underway. Two proteoglycans from
Coriolus versicolor - PSK (Polysaccharide-K) and PSP
(Polysaccharide-Peptide - have demonstrated the most
promise. In Japanese trials since 1970, PSK significantly
extended survival at five years or beyond in cancers
of the stomach, colon-rectum, esophagus, nasopharynx,
and lung (non-small cell types), and in a HLA B40-positive
breast cancer subset. PSP was subjected to Phase II
and Phase III trials in China. In double-blind trials,
PSP significantly extended five-year survival in esophageal
cancer. PSP significantly improved quality of life,
provided substantial pain relief, and enhanced immune
status in 70-97 percent of patients with cancers of
the stomach, esophagus, lung, ovary, and cervix. PSK
and PSP boosted immune cell production, ameliorated
chemotherapy symptoms, and enhanced tumor infiltration
by dendritic and cytotoxic T-cells. Their extremely
high tolerability, proven benefits to survival and quality
of life, and compatibility with chemotherapy and radiation
therapy makes them well suited for cancer management
regimens.
Publication Types:
Review
Review, tutorial
PMID: 10696116, UI: 20161032
1:
Biotherapy 1998;11(4):267-75 |
|
Contribution of cytokines
on the suppression of lung metastasis.
Ishihara Y, Iijima H, Matsunaga K
Department of Hygiene, School of Medicine, Tokyo Women's
Medical University, Japan.
Weekly injection of a protein-bound polysaccharide PSK
in mice with Lewis Lung Cancer (LLC) significantly decreased
the number of lung metastatic foci concomitant with
enhancement of cytostatic activity in the bronchoalveolar
lavage (BAL) cells. These effects were more marked when
the agent was given intratracheally, inducing a larger
number of pulmonary macrophages, lymphocytes and neutrophils
concomitant with increases in BAL tumor necrosis factor-alpha
(TNF-alpha), mouse inflammatory protein-alpha (MIP-1alpha),
mouse inflammatory protein-beta (MIP-1beta), interleukin-1alpha
(IL-1alpha) and interleukin-6 (IL-6), but not interleukin-2
(IL-2) and interleukin-4 (IL-4). Pre-treatment with
anti TNF-alpha antibody reduced these effects. The time
course and production of PSK-induced cytokines were
similar between the tumor-bearing mice and control mice.
BAL neutrophils in mice with LLC showed a tendency toward
acceleration of O2- production compared with circulating
neutrophils. Pulmonary macrophage phagocytosis was also
significantly higher in the LLC mice. These results
suggest that enhancement of cytostasis appears to be
induced by activation and/or improvement of function
in inflammatory and immune cells through cytokines under
immunomodulator treatment in lung metastasis, possibly
via a TNF-alpha-dependent mechanism.
PMID: 9950103, UI: 99133602
1:
Cancer Immunol Immunother 1998 Aug;46(6):338-44 |
|
Polysaccharide K induces
Mn superoxide dismutase (Mn-SOD) in tumor tissues and
inhibits malignant progression of QR-32 tumor cells:
possible roles of interferon alpha, tumor necrosis factor
alpha and transforming growth factor beta in Mn-SOD
induction by polysaccharide K.
Habelhah H, Okada F, Nakai K, Choi SK, Hamada J,
Kobayashi M, Hosokawa M
Laboratory of Pathology, Cancer Institute, Hokkaido
University School of Medicine, Sapporo, Japan.
Previously we reported the malignant progression of
QR-32, a regressor-type tumor clone, following co-implantation
with foreign bodies (gelatin sponge or plastic plate)
in normal syngeneic C57BL/6 mice. We also reported that
the progression of QR-32 cells by a gelatin sponge was
significantly inhibited in the mice administered polysaccharide
K (PSK) and that PSK induced an increase of radical
scavengers, especially manganese superoxide dismutase
(Mn-SOD), locally at the site of tumor tissues. In this
study, to reveal the possible mechanism by which PSK
induced Mn-SOD in the tumor tissues, we examined the
mRNA expression and protein levels of inflammatory cytokines
in the tissues. We found that mRNAs of tumor necrosis
factor alpha (TNFalpha) and interleukin-1alpha (IL-1alpha)
were considerably expressed in both PSK-treated and
phosphate-buffered-saline-treated tumors, and that the
mRNA expression and protein level of interferon gamma
(IFNgamma) increased in the tumor tissues treated with
PSK. In vitro treatment of QR-32 cells with IFNgamma
did not significantly increase the production of Mn-SOD;
however, the combination of IFNgamma with TNFalpha increased
the Mn-SOD production more effectively than did any
of the cytokines used singly. Furthermore, we observed
the down-regulation of the mRNA expression and protein
level of transforming growth factor beta (TGFbeta) in
the tumor tissues treated with PSK, and that in vitro
treatment of QR-32 cells with TGFbeta decreased the
production of Mn-SOD. These results suggest that PSK
suppresses the progression of QR-32 cells by increasing
Mn-SOD via the modulation of inflammatory cytokines;
that is, by decreasing TGF-beta and increasing IFN-gamma.
PMID: 9756418, UI: 98427849
1:
In Vivo 1998 Mar-Apr;12(2):175-82 |
|
The role of neutrophils
as cytotoxic cells in lung metastasis: suppression of
tumor cell metastasis by a biological response modifier
(PSK).
Ishihara Y, Fujii T, Iijima H, Saito K, Matsunaga
K
Department of Hygiene and Public Health (I), Tokyo Women's
Medical College, Japan. ishihara@reserch.twmc.ac.jp
We aimed to determine the role of neutrophils and the
usefulness of a protein-bound polysaccharide (PSK) in
the suppression of tumor cell metastasis in the lung
in vivo. Circulating neutrophils collected frm tumor-bearing
animals (Line-10 hepatocarcinoma) induced a marked decrease
in the size and number of metastatic foci in the lung.
Although pulmonary macrophages (PAMs), lymphocyte and
eosinophil in bronchoalveolar lavage (BAL) fluid increased
following tumor cell inoculation, in addition to these
findings we found that PSK caused an increase in BAL
neutrophil levels causing increased of target cell toxicity
and a marked decrease in the size and the number of
lung metastatic foci. Superoxide anion generation of
blood neutrophils collected from PSK-treated animals
with metastasis showed forward acceleration. The presence
of neutrophil chemotactic factors was confirmed in the
BAL fluid of PSK-treated animals with metastasis, but
not leukotriene B4. The results suggest that modulation
of the tumor cell microenvironment by activation of
neutrophils may prove to be an additional modality in
treatment strategy by combining PSK as a biological
response modifier with conventional therapies for lung
metastasis.
PMID: 9627799, UI: 98291269
1:
Antiviral Res 1997 Aug;35(3):131-8 |
|
In vitro inactivation
of herpes simplex virus by a biological response modifier,
PSK.
Monma Y, Kawana T, Shimizu F
Department of Pediatric Dentistry, Tohoku University
School of Dentistry, Sendai, Japan.
Herpes simplex virus (HSV) causes herpes genitalis,
primary gingivostomatitis and recurrent herpes labialis.
In order to elucidate in vivo mechanisms by which PSK,
a biological response modifier, exerts a protective
effect against HSV infection, we used an in vitro system
to study whether PSK inactivated infectivity of HSV-type
1 (HSV-1) and HSV-type 2 (HSV-2) isolated from patients
with herpes genitalis in addition to a laboratory-cultured
strain of HSV type 1 (HSV-1-GC+). It was found that
HSV-1-GC+ was inactivated by PSK in a dose dependent
fashion of concentrations of PSK and virus titers. Concentrations
of PSK as low as 0.31 mg/ml was shown to inactivate
the infectivity of HSV-1-GC+. Inactivation required
at least 30 min of incubation at 37 degrees C with maximal
inactivation observed at 60 min incubation time. Similar
to HSV-1-GC+, clinically isolated strains of HSV-2 were
inactivated by PSK although clinically isolated strains
of HSV-1 were resistant to PSK, compared with HSV-2.
It was also shown that PSK-treated HSV retained the
ability to adsorb to the cell membrane, but did not
synthesize viral protein(s). These data illustrate that
there is a biological difference in the sensitivity
to PSK between HSV type 1 and type 2, and also suggest
that PSK could inactivate HSV in lesions at peripheral
sites of recurrent herpes.
PMID: 9298752, UI: 97442203
1:
Anticancer Res 1997 Jul-Aug;17(4A):2815-8 |
|
HLA antigen as predictive
index for the outcome of breast cancer patients with
adjuvant immunochemotherapy with PSK.
Yokoe T, Iino Y, Takei H, Horiguchi J, Koibuchi Y,
Maemura M, Ohwada S, Morishita Y
Department of Emergency and Critical Care Medicine,
Gunma University School of Medicine, Japan.
We demonstrated that the prognosis of breast cancer
patients who received adjuvant immunochemotherapy with
Krestin (PSK) showed a tendency to be better than that
of breast cancer patients receiving chemotherapy only.
We retrospectively investigated the usefulness of HLA
typing for selecting patients to receive adjuvant immuno-chemotherapy
with PSK. One hundred and thirty-four patients with
operable breast cancer were typed as HLA-A, -B, -C by
a lymphocytotoxicity test. Patients without vascular
invasion had no adjuvant therapy (NA group). Patients
with vascular invasion in the tumor and/or in the metastatic
lymph node were randomized into two groups. In group
1 (FEMP only), a combination chemotherapy of 100 mg
of 5-fluorouracil (F), 50 mg of cyclophosphamide (E),
2 mg of mitomycin C (M), and 5 mg of predonisolone (P)
was orally administered daily for 28 days (one course).
In group 2 (FEMP+PSK), FEMP and 3.0
g of PSK were orally administered for 28 days
(one course). Two courses a year of these agents were
given for five years in both groups. Each group (NA,
FEMP, FEMP+PSK) was stratified by the presence of HLA
B40 type (B40(+)) or not (B40(-)). Five- and 10-year
disease-free survival (DFS) rates (93%, 80%, respectively)
of patients with B40(+) seemed to be better than those
(83% and 51%) of patients with B40(-). In the NA group,
5- and 10-year DFS were 100% and 71% in patients with
B40(+), 92% and 76% in those with B40(-), respectively.
In the FEMP group (chemotherapy only), 5- and 10-year
DFS of patients with B40(+) were both 84%. These were
not statistically significant compared with those (82%
and 33%) of patients with B40(-). On the other hand,
in the FEMP+PSK group, 5- and 10-year DFS of patients
with B40(+) were both 100%, and those of patients with
B40(-) were 76% and 55%, respectively. DFS of patients
with B40(+) was significantly better than that of patients
with B40(-). It is concluded that HLA typing may be
a predictive index in determining the use of immunochemotherapy
combined with PSK for patients with operable breast
cancer.
Publication Types:
Clinical trial
Randomized controlled trial
PMID: 9252721, UI: 97396530
1:
Gan To Kagaku Ryoho 1997 May;24(7):875-8 |
|
[A case of inoperable
advanced gastric cancer remarkably responding to combined
chemotherapy with UFT-E, MMC and PSK].
[Article in Japanese]
Kogure A, Ishii S, Kakefuda T, Aiura K, Arisawa Y,
Kitagawa Y, Nakagawa M, Shirasugi N, Noga K
Dept. of Surgery, Kawasaki City Hospital.
A 55-year-old male consulted a local doctor with the
complaint of epigastralgia. Examination of the upper
gastrointestinal tract revealed gastric cancer (Borrmann
Type II) and he was referred to our hospital for operation.
A few lymph nodes were palpable in the left supraclavicular
fossa, and the biopsy of those lymph nodes revealed
metastatic adenocarcinoma. The CT scan of the abdomen
showed enlargement of paraaortic lymph nodes. Then,
the patient was determined inoperable (T3, N4, H02 P01,
M1 stage IVb). He was treated as an outpatient with
UFT-E (300 mg/day, orally), Krestin (PSK 3.0 g/day,
orally) and Mitomycin C (MMC 6 or 8 mg once a week,
intravenously repeated interval of 4 weeks). The total
dose of UFT-E, PSK and MMC was 219 g, 1,095 g and 136
mg, respectively. One month later, lymph nodes in the
supraclavicular fossa disappeared, and the lesion in
the stomach completely responded. We have followed the
patient for more than one year. He visits our the outpatient
department and has kept working until now.
PMID: 9170529, UI: 97314187
1:
Cancer Detect Prev 1997;21(1):71-7 |
|
Effect of Krestin as
adjuvant treatment following radical radiotherapy in
non-small cell lung cancer patients.
Hayakawa K, Mitsuhashi N, Saito Y, Nakayama Y, Furuta
M, Nakamoto S, Kawashima M, Niibe H
Department of Radiology and Radiation Oncology, Gunma
University School of Medicine, Japan.
To evaluate the efficacy of Krestin (PSK) as adjuvant
treatment after radical radiation therapy (RT) for non-small
cell lung cancer (NSCLC), treatment results of 225 patients
with NSCLC treated with RT followed by adjuvant administration
of PSK between 1976 and 1989 were analyzed. Of these
patients, 170 (76%) had squamous cell carcinoma. In
the patients with squamous cell carcinoma of the lung,
PSK was given only when the tumor showed satisfactory
shrinkage (complete or partial response) after completion
of RT. The treatment outcomes were compared with those
of the responders to RT not receiving PSK. The 5-year
survival rates of patients with stages I-II and stage
III disease were 39 and 26%, respectively, while the
non-administered responder group's were 17 and 8%. These
differences are statistically significant. An improvement
in the treatment results with combined use of appropriate
immuno-modulating drugs is anticipated in the future.
When clinical trials of the efficacy of these drugs
are conducted, the agents should be given to the patients
with satisfactory tumor regression after RT, although
they still take much time and cost.
Publication Types:
Clinical trial
PMID: 9043766, UI: 97196677