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CancerGuide: Alternative and Complementary Therapies

Evaluating Alternative Therapies
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+ PSK
PSK References
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MedLine Search: PSK, a non-toxic anti-tumor polysaccharide

Legacy MedLine Search

This MedLine Search of the technical medical literature is from the early days of CancerGuide so it may not include the latest research. The articles referenced are still relevant but more recent ones may also be available. For more information on the incredibly powerful and freely available MedLine database see my Article on MedLine.

In all cases I have selected the references that looked most interesting to me. These are searches with a point of view! There could be references on this same subject that I didn't include that you would have. For both of these reasons as well as the age of the search, you may want to consider doing your own search on this subject after looking at mine.

Finally, keep in mind that the abstracts presented here are only summaries of the actual articles. If you want to delve deeper you may want to get some of these articles from a Medical Library or an online document delivery service, as is provided with all MedLine accesses (usually for a fairly substantial fee).


THU SEP 22,1994 9:32 PM

PaperChase Contains 8,517,714 References -- All References Found in the
Following Databases of the National Library of Medicine and the National
Cancer Institute*.  You are searching all four databases simultaneously.

  Database    Indexing Began    Updated     Current through
   MEDLINE        1966          weekly       November 1994 Update, Part 3
   HEALTH         1975          monthly      October 1994 Update
   AIDSLINE       1980          monthly      October 1994 Update
  *CANCERLIT      1980          monthly      September 1994 Update


LIST                    REFERENCES   LIST                     REFERENCES
 A) PSK                        196    C) *SUM AB                     231
 B) KRESTIN                     35


*****BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS*****

(REFERENCE 1 OF 41)
89334864

Sakagami H  Ikeda M  Konno K
Stimulation of tumor necrosis factor-induced human myelogenous
  leukemic cell differentiation by high molecular weight PSK
  subfraction.

In: Biochem Biophys Res Commun (1989 Jul 31) 162(2):597-603

The mouse macrophage-like cell line, J774.1, spontaneously released
  differentiation-inducing factor(s). When these cells were treated
  with a protein-bound polysaccharide, PSK, significantly higher
  amounts of differentiation-inducing activity were accumulated in the
  culture supernatant. PSK directly stimulated human myelogenous
  leukemic cell differentiation induced by J774.1 conditioned medium or
  by tumor necrosis factor. Among four subfractions of PSK, only the
  highest molecular weight fraction (MW greater than 200 kD) exerted
  such a stimulating effect.

Institutional address:
     First Department of Biochemistry
     School of Medicine
     Showa University
     Tokyo
     Japan.


*****JAPANESE JOURNAL OF CANCER RESEARCH*****

(REFERENCE 2 OF 41)
92388016

Ebina T  Murata K
Antitumor effect of PSK at a distant site: tumor-specific immunity
  and combination with other chemotherapeutic agents.

In: Jpn J Cancer Res (1992 Jul) 83(7):775-82

The antitumor effect of PSK, a Coriolus preparation, was analyzed
  with the double grafted tumor system in which BALB/c mice received
  intradermal inoculations of syngeneic Meth-A fibrosarcoma in the
  right (primary tumor, 10(6) cells) and left (distant tumor, 2 x 10(5)
  cells) flanks. Intratumoral administration of PSK significantly
  inhibited the growth of not only the right but also the left tumor.
  PSK also inhibited the growth of a methylcholanthrene-induced
  fibrosarcoma BAMC-1, and a methylurethane-induced adenocarcinoma
  Colon 26 in the double grafted tumor system of syngeneic BALB/c mice.
  However, when the left distant tumor was different from the right
  Meth-A tumor, the intratumoral administration of PSK in the right
  tumor was unable to inhibit the growth of the left BAMC-1 or RL male-
  1 tumor. The PSK-induced immunity, therefore, is tumor-specific and T
  lymphocytes may play an important role in antitumor memory function.
  The enhancement of concomitant immunity by PSK treatment was
  completely impaired by previous intravenous administration of an
  alkylating agent, cyclophosphamide (CY). The enhancement of
  sinecomitant immunity by PSK treatment was also impaired by previous
  CY intravenous administration. The antitumor effect of PSK was
  suppressed by previous intravenous administration of another
  alkylating agent, ACNU. It is possible that alkylating agents
  suppress the function of effector T cells and granulocytes which are
  very important for the antitumor immune cascade reaction due to PSK
  treatment. On the other hand, the antitumor effect of PSK was
  enhanced by previous intravenous administration of an anti-
  metabolite, 5-fluorouracil.

Institutional address:
     Department of Bacteriology
     Tohoku University School of Medicine
     Sendai.

(REFERENCE 3 OF 41)
92041203

Kariya Y  Okamoto N  Fujimoto T  Inoue N  Kihara T  Sugie K  Yagita M
  Kanzaki H  Mori T  Uchida A
Lysis of fresh human tumor cells by autologous peripheral blood
  lymphocytes and tumor-infiltrating lymphocytes activated by PSK.

In: Jpn J Cancer Res (1991 Sep) 82(9):1044-50

The protein-bound polysaccharide PSK was tested for the ability to
  induce in vitro autologous tumor killing (ATK) activity in human
  cancer patients. Peripheral blood lymphocytes (PBL) and tumor-
  infiltrating lymphocytes (TIL) demonstrated various levels of
  cytotoxicity against autologous, freshly isolated tumor cells. When
  PBL and TIL were cultured overnight with PSK, ATK activity was
  induced in previously non-reactive cases and augmented in previously
  reactive samples. The PSK effect was observed with PSK concentrations
  of 10-100 micrograms/ml that could be obtained in the blood of cancer
  patients who received standard oral administration of PSK. The
  manifestation of PSK-induced ATK required active cell metabolism and
  RNA and protein syntheses, but not DNA synthesis of lymphocytes. PSK-
  induced enhancement of ATK was not abrogated by monoclonal antibodies
  (mAb) directed against interferon (IFN) alpha or IFN gamma. In
  addition, mAb that neutralized interleukin-2 (IL-2) or mAb reactive
  with alpha-chain or beta-chain of IL-2 receptors (IL-2R) had no
  effect on PSK-induced ATK activity. Supernatants from PSK-stimulated
  lymphocyte cultures did not induce ATK. Cell fractionation
  experiments revealed that CD3-CD16+ large granular lymphocytes (LGL)
  and/or CD3+CD16- T lymphocytes were responsible for both spontaneous
  and PSK-induced ATK. PSK-activated LGL, but not T lymphocytes
  expressed lysis of fresh allogeneic tumor cells. These results
  indicate that PSK activates PBL and TIL to exhibit ATK independently
  of IL-2/IL-2R systems.

Institutional address:
     Department of Late Effect Studies
     Kyoto University.

(REFERENCE 4 OF 41)
89254785

Ebina T  Kohya H  Ishikawa K
Antitumor effect of PSK: role of regional lymph nodes and enhancement
  of concomitant and sinecomitant immunity in the mouse.

In: Jpn J Cancer Res (1989 Feb) 80(2):158-66

PSK, a Coriolus preparation, inhibited the growth of not only the
  right but also the left, non-treated tumor in a double grafted tumor
  system. In order to examine the role of lymph nodes and the spleen in
  the antitumor activity of PSK, regional (axillary and inguinal) lymph
  nodes and spleen were resected. Since in resected mice the antitumor
  activity of PSK against the right and left tumors was weakened, the
  regional lymph nodes and the spleen probably have a very important
  role in the antimetastatic effect of intratumoral administration of
  PSK. TIL (tumor-infiltrating lymphocytes) obtained from left and
  right side tumors treated with PSK were examined by Winn assay for
  their antitumor activity against Meth-A sarcoma in BALB/c mice. TIL
  from both sides clearly inhibited the growth of admixed Meth-A cells,
  but control TIL did not. A primary growth of Meth-A sarcoma
  inoculated into the right flank resulted in the generation of
  concomitant immunity to the growth of a second graft of the same
  tumor cells in the left flank. A significant inhibitory effect on the
  proliferation of the tumor cells inoculated secondarily was shown in
  mice bearing a primary right tumor that had previously been
  inoculated with PSK 3 times. After surgical excision of the primary
  tumor on day 6, daily oral administration of PSK significantly
  inhibited the growth of the secondary tumor inoculated on day 21,
  that is, PSK treatment also enhanced sinecomitant immunity. These
  observations suggest that presurgical intratumoral injection and
  postoperative oral administration of PSK are highly effective in
  eradicating metastatic tumors.

Institutional address:
     Department of Bacteriology
     Tohoku University School of Medicine
     Sendai.

(REFERENCE 5 OF 41)
88186531

Kikuchi Y  Kizawa I  Oomori K  Iwano I  Kita T  Kato K
Effects of PSK on interleukin-2 production by peripheral lymphocytes
  of patients with advanced ovarian carcinoma during chemotherapy.

In: Jpn J Cancer Res (1988 Jan) 79(1):125-30

The effects of PSK on OKT 4/OKT 8 cell ratio, interleukin-2 (IL-2)
  production and expression of IL-2 receptor were examined in
  peripheral blood lymphocytes (PBL) from patients with advanced
  ovarian cancer during the course of chemotherapy. Preoperative levels
  of OKT 4/OKT 8 cell ratio and IL-2 production in PBL from patients
  with advanced ovarian cancer were significantly lower than those in
  cases of benign ovarian tumor. However, the expression of IL-2
  receptor did not show any significant difference between ovarian
  cancer and benign ovarian tumor patients. When a combination
  chemotherapy of cisplatin, adriamycin and cyclophosphamide was given,
  the OKT 4/OKT 8 cell ratio was significantly increased with a
  significant decrease of the absolute number of the OKT 8 cell subset,
  while the expression of IL-2 receptor and the absolute number of the
  OKT 4 cell subset remained unchanged. In contrast, the IL-2
  production was markedly depressed after the first course of
  chemotherapy. When PSK was combined with combination chemotherapy,
  the degree of inhibition of IL-2 production was reduced (though the
  effect was not statistically significant). If treatment with PSK was
  initiated after completion of combination chemotherapy, in addition
  to a significant elevation of OKT 4/OKT 8 cell ratio the depressed IL-
  2 production was restored to benign control levels. On the other
  hand, the expression of IL-2 receptor remained unchanged even if PSK
  was given after completion of chemotherapy.

Institutional address:
     Department of Obstetrics and Gynecology
     National Defense Medical College
     Saitama.


*****LANCET*****

(REFERENCE 6 OF 41)
94239027

Nakazato H  Koike A  Saji S  Ogawa N  Sakamoto J
Efficacy of immunochemotherapy as adjuvant treatment after curative
  resection of gastric cancer. Study Group of Immunochemotherapy with
  PSK for Gastric Cancer.

In: Lancet (1994 May 7) 343(8906):1122-6

In Japan the standard adjuvant treatment after resection of gastric
  cancer is intravenous mitomycin plus oral fluorouracil. We have
  assessed the efficacy of protein-bound polysaccharide (PSK) in
  addition to standard chemotherapy in patients who had undergone
  curative gastrectomy at 46 institutions in central Japan. 262
  patients were randomly assigned standard treatment alone or with PSK.
  The minimum follow-up time was 5 years (range 5-7 years). PSK
  improved both the 5-year disease-free rate (70.7 vs 59.4% in standard
  treatment group, p = 0.047) and 5-year survival (73.0 vs 60.0%, p =
  0.044). The two regimens had only slight toxic effects, consisting of
  nausea, leucopenia, and liver function impairment, and there were no
  significant differences between the groups. The treatments were
  clinically well tolerated and compliance was good. Addition of PSK to
  adjuvant chemotherapy with mitomycin and fluorouracil is beneficial
  as treatment after curative gastrectomy.

Institutional address:
     Yokoyama Gastrointestinal Hospital
     Japan.


*****RECENT RESULTS IN CANCER RESEARCH*****

(REFERENCE 7 OF 41)
79224859

Taguchi T
Clinical studies on PSK: combination therapy of PSK with surgery and
  chemotherapy.

In: Recent Results Cancer Res (1978) 68:236-40

[No Abstract Available]

(REFERENCE 8 OF 41)
79224849

Taguchi T
Clinical studies on PSK: combination therapy of PSK with radiation in
  cancer of the uterine cervix.

In: Recent Results Cancer Res (1978) 68:174-7

[No Abstract Available]


*****ANTICANCER RESEARCH*****

(REFERENCE 9 OF 41)
92675773

Sakagami H  Kawazoe Y
NOVEL ELUCIDATION OF THE MECHANISM OF INDUCTION OF VARIOUS
  IMMUNOPOTENTIATING ACTIVITIES BY A PROTEIN-BOUND POLYSACCHARIDE, PSK
  (MEETING ABSTRACT)

In: Anticancer Res (1990) 10(5B):1472

A protein-bound polysaccharide, PSK, extracted from the mycelium of
  Coriolus versicolor (Fr) Quel, has been recognized for its host-
  mediated antitumor and antimicrobial activity in mice. Since PSK is a
  plant extract, it could contain several active ingredients. However,
  intact PSK has been used in almost all experiments. We recently
  reported that, among the four subfractions separated by the mol wt,
  only the highest mol wt fraction, F4 (mol wt greater than 200 kD),
  induced significant antimicrobial activity in mice. PSK and F4
  stimulated the differentiation of human myelogenous leukemia cell
  lines toward monocyte/macrophages, induced by various cytokines such
  as tumor necrosis factor (TNF) and interferon-r (IFN-r). Binding
  studies with 125I-TNF or 125I-IFN-r suggest that the stimulating
  effect of the active PSK subfractions might be associated with
  inhibition of the downregulation of receptor binding of these
  cytokines. PSK also stimulated the iodination (incorporation of
  radioactive iodine into an acid-insoluble fraction) of human
  peripheral blood polymorphonuclear cells (PMN), and the NBT-reducing
  activity of mouse peritoneal resident macrophages. Among the
  subfractions of PSK, whether separated by mol wt or by isoelectric
  point precipitation, the highest mol wt fraction F4, and the fraction
  precipitated at pH 4.0-4.5 (Fr 4), stimulated macrophage NBT-reducing
  activity and PMN iodination most. In contrast, natural and chemically
  modified glucans had little or no stimulating activity. We recently
  found that iv administration of PSK significantly stimulated OK-432-
  elicited endogenous cytotoxic factor (possibly TNF) production in
  mouse serum. The data suggest that (1) immunopotentiation activity of
  PSK might be ascribed, at least in part, to the stimulation or
  production of various cytokines, and (2) PSK might have some unique
  component(s) which directly stimulate the macrophage/PMN function.
  Therefore, the necessity of an advanced structure-activity
  relationship is indicated and further studies of this need are
  underway in our laboratory.

Institutional address:
     First Dept. of Biochemistry
     Sch. of Medicine
     Showa Univ.
     1-5-8 Hatanodai
     Shinagawaku
     Tokyo 142
     Japan

(REFERENCE 10 OF 41)
87324781

Matsunaga K  Morita I  Oguchi Y  Fujii T  Yoshikumi C  Nomoto K
The effect of a biological response modifier, PSK, on the intestinal
  immune system in tumor-bearing mice.

In: Anticancer Res (1987 May-Jun) 7(3 Pt B):509-12

We have previously shown that oral administration of PSK not only
  exerts antitumor activity, but also restores immune response in tumor-
  bearing mice. In order to analyze the immunomodulative effect of PSK,
  we investigated the effects of oral PSK on the intestinal immune
  systems in ICR mice bearing sarcoma 180. Oral administration of PSK
  increased the number of Peyer's patches that developed relatively
  well, and led to recovered mitogenic response of lymphocytes from gut-
  associated lymphatic tissue and responsiveness to oral
  preimmunization with SRBC in tumor-bearing mice. These results
  suggest that PSK modulates the immunity in intestinal tract of tumor-
  bearing mice.

Institutional address:
     Biomedical Research Laboratories
     Kureha Chemical Industry Co.
     Ltd.
     Tokyo
     Japan.

(REFERENCE 11 OF 41)
94091790

Hayakawa K  Mitsuhashi N  Saito Y  Takahashi M  Katano S  Shiojima K
  Furuta M  Niibe H
Effect of krestin (PSK) as adjuvant treatment on the prognosis after
  radical radiotherapy in patients with non-small cell lung cancer.

In: Anticancer Res (1993 Sep-Oct) 13(5C):1815-20

From 1976 to 1985, 185 patients with non-small cell lung cancer at
  stages I-III were treated with definitive radiotherapy in Gunma
  University Hospital. As a result of analyzing the long-term survivors
  treated with radiotherapy, suitable conditions of the patients for
  radical radiotherapy were as follows; 1) stage I or II, and some
  stage III, 2) as regards the histologic type epidermoid carcinoma or
  well-differentiated adenocarcinoma, 3) as regards the primary sites,
  the upper lobe and the superior segment of the lower lobe, 4) the
  optimum dose was 60-70Gy, 5) the size of the radiation fields given >
  40Gy was 100 cm2 or less, and 6) the host condition was satisfactory
  (BRM combined use). In particular, as a result of administering PSK
  as adjuvant treatment to patients with epidermoid carcinoma of the
  lung showing satisfactory tumour shrinkage after radiotherapy, the
  five year survival rate of the patients with stages I or II disease,
  as well as stage III was 39% and 22% respectively, compared with the
  non-administered group's 16% and 5%. These differences are
  statistically significant. Although an improvement in the results of
  treatment with the combined use of appropriate BRMs is anticipated in
  the future, when clinical trials for combined BRM and radiotherapy
  are planned, the subjects should be patients with satisfactory tumour
  regression after radiotherapy.

Institutional address:
     Department of Radiology and Radiation Oncology
     Gunma University School of Medicine
     Japan.

(REFERENCE 12 OF 41)
93199236

Iino Y  Takai Y  Sugamata N  Morishita Y
PSK (krestin) potentiates chemotherapeutic effects of tamoxifen on
  rat mammary carcinomas.

In: Anticancer Res (1992 Nov-Dec) 12(6B):2101-3

A total of 20 mg of 7,12-dimethylbenz[a]anthracene (DMBA) was
  administered orally to 41 female Sprague-Dawley (SD) rats (control
  group), and 60 mg/kg of Krestin (PSK) were orally administered daily
  to 38 rats (PSK group) after DMBA administration. The average
  development period (9.6 weeks) of DMBA-induced tumors in the PSK
  group was significantly longer (P < 0.02) than that (7.9 weeks) in
  the control group. Average estrogen receptor (ER) levels of
  established tumors were almost the same between these two groups.
  However, the chemotherapeutic effect of tamoxifen (TAM) was
  significantly enhanced by PSK pretreatment.

Institutional address:
     Second Departmen of Surgery
     Gunma University School of Medicine
     Japan.

(REFERENCE 13 OF 41)
91290790

Sakagami H  Aoki T  Simpson A  Tanuma S
Induction of immunopotentiation activity by a protein-bound
  polysaccharide, PSK (review).

In: Anticancer Res (1991 Mar-Apr) 11(2):993-9

A protein-bound polysaccharide, PSK, extracted from the mycelium of
  Coriolus versicolor (Fr.) Quel, has been recognized for its host-
  mediated induction of antitumor and antimicrobial activities in mice.
  Intravenous administration of PSK, in association with OK-432
  (Picibanil), transiently induced endogenous production of a cytotoxic
  factor (CF) (possibly tumor necrosis factor, TNF) in normal mice. The
  ability to produce CF depended greatly on both dose and interval
  between administration of the PSK and OK-432. Although PSK has been
  reported to contain several active ingredients, unfractionated PSK
  has been used in almost all experiments performed so far. We recently
  reported that, of the four subfractions separated by successive
  filtration through membrane filters, only the highest molecular
  weight fraction F4 (MW greater than 200 kD) induced significant
  antimicrobial activity in mice. PSK stimulated the NBT-reducing
  activity of mouse peritoneal macrophages and the iodination
  (incorporation of radioactive iodine into an acid-insoluble fraction)
  of human peripheral blood polymorphonuclear cells (PMN). Among the
  subfractions of PSK, the highest molecular weight fraction F4, and
  the fraction precipitated at pH 4.0-4.5 (Fr. 4), stimulated
  macrophage NBT-reducing activity and PMN iodination most. In
  contrast, natural and chemically modified glucans had little or no
  stimulating activity. PSK, F4 or Fr. 4 additively or synergistically
  stimulated TNF-induced cytotoxicity against L-929 cells,
  differentiation of human myelogenous leukemia cell lines toward
  monocytes/macrophages, and iodination of human peripheral blood PMN.
  The active PSK subfractions significantly reduced the down regulation
  of specific 125I-TNF or 125I-IFN-gamma binding to cellular receptors.
  These data suggest that (i) immunopotentiation activity of PSK might
  be ascribed, at least in part, to stimulation of cytokine action and
  production, and (ii) PSK might have some unique structural features.

Institutional address:
     First Department of Biochemistry
     School of Medicine
     Showa University
     Tokyo
     Japan.


*****BIOTHERAPY*****

(REFERENCE 14 OF 41)
92322392

Nio Y  Tsubono M  Tseng CC  Morimoto H  Kawabata K  Masai Y
  Shiraishi T  Imai S  Ohgaki K  Tobe T
Immunomodulation by orally administered protein-bound polysaccharide
  PSK in patients with gastrointestinal cancer.

In: Biotherapy (1992) 4(2):117-28

The present study was designed to assess the effects of the protein-
  bound polysaccharide PSK on the immunological status of patients with
  gastrointestinal cancer. Twenty-nine gastric and 18 colorectal cancer
  patients were randomly assigned to either the control or PSK group.
  Patients in the PSK group were given 3.0 g of PSK orally before
  surgery, either daily or every other day. Patients in the control
  group received no PSK. The data of peripheral blood lymphocytes (PBL)
  were compared before and after administration of PSK, and those of
  the regional node lymphocytes (RNL) were compared between the control
  and the PSK group. The results indicate that the effects of PSK were
  significantly influenced by the duration of administration, but not
  by the frequency of administration. In the patients belonging to the
  short term PSK group (administration less than 14 days), the response
  of the PBL to PSK and Con A become significantly stronger compared to
  before the administration of PSK, whereas the cytotoxicity against
  K562 and KATO-3, and the proportion of CD16+ cells increased
  significantly in those patients belonging to the long term PSK group
  (greater than or equal to 14 days). In addition, the proportion of
  CD9 + 11b + suppressor T cells decreased in the RNL of the short term
  PSK group, whereas the proportion of CD4 + Leu8 - helper T cells in
  the RNL increased in the long term PSK group. These results suggest
  that the oral administration of PSK leads to the suppression of
  suppressor cells in the RNL.(ABSTRACT TRUNCATED AT 250 WORDS)

Institutional address:
     First Department of Surgery
     Kyoto University Faculty of Medicine
     Japan.


*****CANCER*****

(REFERENCE 15 OF 41)
93046011

Toi M  Hattori T  Akagi M  Inokuchi K  Orita K  Sugimachi K  Dohi K
  Nomura Y  Monden Y  Hamada Y  et al
Randomized adjuvant trial to evaluate the addition of tamoxifen and
  PSK to chemotherapy in patients with primary breast cancer. 5-Year
  results from the Nishi-Nippon Group of the Adjuvant Chemoendocrine
  Therapy for Breast Cancer Organization.

In: Cancer (1992 Nov 15) 70(10):2475-83

BACKGROUND. A randomized adjuvant trial was conducted from October
  1982 to January 1985 to evaluate the addition of tamoxifen (TAM) to
  combination chemotherapy with perioperative mitomycin C (MMC) and
  ftorafur (FT) for patients with estrogen receptor (ER)-positive
  tumors and the addition of PSK, a biologic response modifier, to
  MMC+FT chemotherapy for patients with ER-negative tumors in operable
  Stage IIA, IIB, and IIIA cancer. The doses used were 20 mg of oral
  TAM daily, 600 mg of oral FT daily, and 3 g of oral PSK daily for 2
  years. Intravenous MMC (13 mg/m2) was given on the day of operation.
  METHODS. A total of 967 patients were entered and randomized by
  stratification based on ER status and staging (1978 International
  Union Against Cancer [UICC] criteria at the time of trial execution).
  Of 967 patients, 914 (94.5%) were evaluable. At 5-year follow-up,
  significant prolonged overall survival (OS) and relapse-free survival
  (RFS) times were seen with the addition of TAM in patients with ER-
  positive and Stage IIIA T3N0 cancer (1987 UICC-American Joint
  Committee on Cancer [AJCC] criteria); however, no significant
  survival benefit from TAM was seen in patients with ER-positive and
  Stage IIA T2N1 cancer. There was no significant difference between
  regimens, with or without PSK, in patients with ER-negative disease.
  RESULTS. Results of subset analyses suggested a benefit from TAM in
  postmenopausal patients with ER-positive and Stage IIA T2N1 cancer
  and a benefit from PSK in patients with node-negative, ER-negative,
  and Stage IIA T2N1 cancer. CONCLUSIONS. The 5-year results of the
  current trial showed a survival advantage by the addition of TAM to
  chemotherapy in patients with ER-positive and Stage IIIA T3N0 cancer.

Institutional address:
     Department of Surgery
     Hiroshima University
     Japan.


*****CANCER EPIDEMIOLOGY, BIOMARKERS AND PREVENTION*****

(REFERENCE 16 OF 41)
93306183

Kobayashi H  Matsunaga K  Fujii M
PSK as a chemopreventive agent.

In: Cancer Epidemiol Biomarkers Prev (1993 May-Jun) 2(3):271-6

PSK, a protein-bound polysaccharide preparation obtained from
  cultured mycelia of the CM-101 strain of Coriolus versicolor
  belonging to basidiomycetes, is a biological response modifier
  capable of exhibiting diverse biological activities. This agent has
  been used clinically for the treatment of postoperative cancer
  patients in Japan by oral use. In this paper, chemopreventive aspects
  of PSK were reviewed. Oral administration of PSK reduced the
  incidence of tumor and/or prolonged the survival period in the
  following chemical carcinogen-induced, radiation-induced, and
  spontaneously developed animal cancer models: rat gastrointestinal
  cancer induced by 1,2-dimethylhydrazine; rat hepatoma by 3'-methyl-
  dimethylaminobenzene; mouse thymic lymphoma by whole-body
  irradiation; mouse spontaneous mammary tumor; and so on. PSK did not
  interact and/or inhibit drug-metabolizing enzymes and had no effect
  on the Ames test. On the other hand, this agent scavenged active
  oxygen through the induction of manganese superoxide dismutase,
  prevented the increase in frequency of anticancer agent-induced
  sister chromatid exchange, and suppressed fetal deformation induced
  by transplacental injection of teratogen, suggesting an effect on the
  initiation or promotion process of carcinogenesis. Also, PSK
  regulated cytokine production and enhanced the antitumor activity of
  effector cells such as killer T-cells and natural killer cells,
  suggesting an effect on the growth process after the development of
  malignant cells. Thus, this agent seems to act at multiple steps
  during carcinogenesis rather than a particular step. The main
  mechanism may be an antiteratogenic effect attributed to radical
  trapping, preventive effects against chromosome injury, and
  immunomodulative effects attributed to the modulation of cytokine
  production and effector cell function.(ABSTRACT TRUNCATED AT 250
  WORDS)

Institutional address:
     Higashi-Nihon Gakuen University
     Hokkaido
     Japan.


*****CANCER IMMUNOLOGY, IMMUNOTHERAPY*****

(REFERENCE 17 OF 41)
90329611

Torisu M  Hayashi Y  Ishimitsu T  Fujimura T  Iwasaki K  Katano M
  Yamamoto H  Kimura Y  Takesue M  Kondo M  et al
Significant prolongation of disease-free period gained by oral
  polysaccharide K (PSK) administration after curative surgical
  operation of colorectal cancer.

In: Cancer Immunol Immunother (1990) 31(5):261-8

To examine the clinical efficacy and the mechanism of action of
  polysaccharide K (PSK), a protein-bound polysaccharide extracted from
  a Basidiomycetes fungus, a randomized double-blind trial was
  performed by administering PSK to 56 patients and a placebo to
  another group of 55 patients after surgical operations on their
  colorectal cancers. The rate of patients in remission (or disease-
  free) was significantly higher in the PSK group than in the placebo
  group; the difference between both groups was statistically
  significant at P less than 0.05 by the log-rank test. The survival
  rate of patients was also significantly (P less than 0.05) higher in
  the PSK group than in the control group. The most significant
  laboratory finding was that polymorphonuclear leukocytes from PSK-
  treated patients showed remarkable enhancement in their activities,
  such as random and/or chemotactic locomotion, and phagocytic
  activity, when compared with those in the control group. In
  conclusion, PSK was useful as a maintenance therapy for patients
  after their curative surgical operations for colorectal cancer. The
  beneficial effects were probably due to the activation of leukocyte
  functions as one of the many biological-response-modifying
  (activities induced by PSK).

Institutional address:
     First Department of Surgery
     Kyushu University School of Medicine
     Fukuoka
     Japan.


*****CANCER TREATMENT REVIEWS*****

(REFERENCE 18 OF 41)
85048816

Tsukagoshi S  Hashimoto Y  Fujii G  Kobayashi H  Nomoto K  Orita K
Krestin (PSK).

In: Cancer Treat Rev (1984 Jun) 11(2):131-55

A polysaccharide preparation isolated from Coriolus versicolor (Fr.)
  Quel. of Basidiomycetes (PSK) predominantly consists of glucan and
  approximately 25% tightly bound protein. PSK was effective against
  various allogeneic and syngeneic animal tumors and has been given
  orally to cancer patients. Various suppressed or enhanced immune
  responses of tumor-bearing animals were restored to normal levels by
  the administration of PSK in the tumor models tested. The killer T
  cell activity was augmented in tumor-bearing mice by intraperitoneal
  or oral administration of PSK, and there was correlation between the
  PSK associated antitumor effect and the killer T cell activity. It
  was found that PSK competed with immunosuppressive substances
  isolated from tumor-bearing mice and that the intestinal immune
  system appeared to be modulated by oral administration of PSK. After
  oral administration of 14C- or 35S-labeled PSK to normal rats, it was
  found that small or large molecular substances appeared in the serum
  depending on the time elapsed after administration, an indication
  that large molecular size products were from the digestive tract.

Institutional address:
     Cancer Chemotherapy Center
     Japanese Foundation for Cancer Research
     Tokyo.


*****DISEASES OF THE COLON AND RECTUM*****

(REFERENCE 19 OF 41)
92136955

Mitomi T  Tsuchiya S  Iijima N  Aso K  Suzuki K  Nishiyama K  Amano T
  Takahashi T  Murayama N  Oka H  et al
Randomized, controlled study on adjuvant immunochemotherapy with PSK
  in curatively resected colorectal cancer. The Cooperative Study Group
  of Surgical Adjuvant Immunochemotherapy for Cancer of Colon and
  Rectum (Kanagawa).

In: Dis Colon Rectum (1992 Feb) 35(2):123-30

A randomized, controlled trial of adjuvant immunochemotherapy with
  PSK (Kureha Chemical Industry Co., Tokyo, Japan) in curatively
  resected colorectal cancer was studied in 35 institutions in the
  Kanagawa prefecture. From March 1985 to February 1987, 462 patients
  were registered. Four hundred forty-eight of those patients (97.0
  percent) satisfied the eligibility criteria. The control group
  received mitomycin C intravenously on the day of and the day after
  surgery, followed by oral 5-fluorouracil (5-FU) administration for
  over six months. The PSK group received PSK orally for over three
  years, in addition to mitomycin C and 5-FU as in the control group.
  At the end of February 1990, the median follow-up time for this study
  was four years (range, three to five years). The disease-free
  survival curve and the survival curve of the PSK group were better
  than those of the control group, and differences between the two
  groups were statistically significant (disease-free survival, P =
  0.013; survival, P = 0.013). These results indicate that adjuvant
  immunochemotherapy with PSK was beneficial for curatively resected
  colorectal cancer.

Institutional address:
     Department of Surgery II
     Tokai University
     Kanagawa
     Japan.


*****EXS*****

(REFERENCE 20 OF 41)
92314622

Kumar S  Saitoh K  Kumar P
Antiangiogenesis strategies in cancer therapy with special reference
  to Krestin.

In: EXS (1992) 61:463-70

[No Abstract Available]

Institutional address:
     Christie Hospital (NHS) Trust
     Manchester
     England.


*****GAN TO KAGAKU RYOHO [JAPANESE JOURNAL OF CANCER AND CHEMOTHERAPY]*****

(REFERENCE 21 OF 41)
80685645

Tanaka T  Shirosaki H  Kamimoto M  Nishimura I  Baba N  Hirose M
[LONG-TERM ADMINISTRATION OF PSK AS AN IMMUNOSTIMULANT: AN
  IMMUNOLOGICAL CONSIDERATION]

In: Gan To Kagaku Ryoho (1980) 7(4):638-644  (Published in Japanese)

Long-term administration of PSK was given to 35 patients with cancer
  of the digestive organs and breast during the so-called maintenance
  period or the follow-up period. The mean duration of administration
  was about 9 mo. Delayed skin tests (purified protein derivative,
  candida) and id phytohemagglutinin tests tended to be initially
  enhanced, slightly depressed after several mo, and then restored
  about 3 mo later, in spite of continuous administration. The
  peripheral lymphocyte counts were also increased after a decrease.
  Serum IgG, IgA, and IgM were less changed, but IgM and IgG were
  slightly increased, but only in the curatively resected cases. No
  side effect in the liver, bone marrow, or other organs was seen.
  These results indicate that PSK is useful as an immunostimulant in
  cancer therapy. Relatively short periods of alternation of PSK with
  some other stimulant is assumed to be better than continuous
  administration of PSK alone. (Author abstract) (7 Refs)

Institutional address:
     Dept. Surgery
     Fukui Red Cross Hosp.
     Tsukimi
     Fukui 910
     Japan

(REFERENCE 22 OF 41)
80669104

Kato H  Yokoe N  Takemura S  Hotta T  Matsumura N  Furukawa Y
  Wakamatsu Y  Nishihori H  Ikezaki M  Hosokawa K  Yoshikawa T  Kondo M
[EFFECT OF IMMUNOPOTENTIATORS OK-432 (PICIBANIL), PSK (KRESTIN), AND
  LEVAMISOLE ON HUMAN SERUM COMPLEMENT]

In: Gan To Kagaku Ryoho (1979) 6(3):643-649 1979  (Published in Japanese)

The mode of antitumor action of the so-called immunopotentiators has
  been explained as restoration of the impaired immune response through
  cellular immunity. Since most of the preparations available are of
  bacterial or plant origin, it is possible that they can activate the
  complement system mainly through its alternative pathway. The purpose
  of the present investigation is to demonstrate the effect of a
  streptococcal preparation Picibanil (OK-432), a protein
  polysaccharide from mycelia of Coriolus versicolor Krestin (PSK), and
  an aminothiazole derivative Levamisole on human serum complement in
  vivo. Aged patients without malignancy, who had a decreased immune
  response, as detected by purified protein derivative and
  phytohemagglutinin skin tests received sc injection of OK-432 0.l
  mg/day, po PSK 3 g/day or po Levamisole 150 mg/day on three
  consecutive days of each wk. The classical complement pathway was
  determined by the lysis of sensitized sheep RBC [50% hemolytic unit
  for complement hemolysis, (CHO-50)] and the alternative pathway by
  the lysis of unsensitized rabbit RBC [50% hemolytic unit for
  alternative complement hemolysis, (ACH-50)]. The complement
  components were measured by the single radial immunodiffusion method.
  It was found that the administration of OK-432, PSK, or Levamisole
  resulted in the elevation of serum CH50 and ACH50. Complement
  components were affected by the use of the preparations, while no
  specific tendency could be demonstrated, except for increased C3
  level when OK-432 was given. Oral administration of PSK showed the
  conversion of C3 from beta 1C to beta 1A mobility, determined by
  crossed immunoelectrophoresis. Evidence that immunopotentiators
  increase the serum complement level in man leads to the conclusion
  that these drugs might have an additional function in potentiating
  the host-mediated immune response against malignant tumor via the
  complement system. (Author abstract) (22 Refs)

Institutional address:
     Third Dept. Internal Medicine
     Kyoto Prefectural Univ. Medicine
     Kamikyo-ku
     Kyoto 602
     Japan

(REFERENCE 23 OF 41)
90120624

Nishiwaki Y  Furuse K  Fukuoka M  Ota M  Niitani H  Asakawa M  Nakai H
  Sakai S  Ogawa N
[A randomized controlled study of PSK combined immuno-chemotherapy
  for adenocarcinoma of the lung. The Advanced Lung Cancer Immuno-
  chemotherapy Study Group]

In: Gan To Kagaku Ryoho (1990 Jan) 17(1):131-6  (Published in Japanese)

In a randomized controlled study of chemotherapy (CDDP 100 mg/m2 day
  1, VDS 3 mg/m2 day 1, 8, 15) vs. immuno-chemotherapy combined with
  PSK 3 g/day for adenocarcinoma of the lung (stage III, IV, p. s. 0,
  1, 2), response rate for 169 cases with completed extramural review
  was 14.2%. As for the response rates for 138 complete cases, the
  chemotherapy group showed 17.9%, and the immuno-chemotherapy group
  was 16.9%. MST were 330 days and 331 days, respectively. In stage III
  cases, the response rates were 11.1% in the chemotherapy group and
  37.5% in the immuno-chemotherapy group (p = 0.046). MST were 457 days
  (65.3 weeks) and 576 days (82.3 weeks), respectively. In terms of
  survival curve, it was suggested that the immuno-chemotherapy group
  was superior to the chemotherapy group (logrank test p = 0.075), but
  in stage IV cases, there was nothing outstanding in the
  immunochemotherapy group.

Institutional address:
     National Matsudo Hospital
     Dept. of Internal Med.

(REFERENCE 24 OF 41)
86294568

Oguchi Y  Morita I  Matsunaga K  Fujii T  Yoshikumi C  Kawai Y
  Nomoto K
[Involution of the thymus in tumor-bearing mice and its restoration
  by PSK (2)]

In: Gan To Kagaku Ryoho (1986 Aug) 13(8):2645-52  (Published in Japanese)

We examined the effect of PSK on involution of the thymus in tumor-
  bearing mice. The weight and cell number of the thymus decreased and
  the size distribution (scatter profile) of thymus cells was changed
  in X5563-bearing C3H/He mice. Also in these mice, 3H-thymidine
  incorporation into the thymus was reduced compared with that in
  control mice, as evaluated not only by per organ but also by per 1 mg
  of thymus tissue. Such an involution was also observed in tumor-free
  mice injected with immunosuppressive substance, which had been
  obtained from ascites of X5563-bearing mice and revealed suppressive
  activity against lymphocyte proliferation. PSK administration
  prevented such modulation in the thymus of tumor-bearing mice and
  immunosuppressive substance-injected tumor-free mice. In other words,
  it is considered that the various changes in the thymus demonstrated
  in tumor-bearing mice may be attributable to the suppression of cell
  proliferation in the thymus, that such suppression is caused at least
  partly by an immunosuppressive substance which possesses inhibitory
  activity against lymphocyte proliferation, and that PSK has an
  antagonistic activity against such a substance so as to restore the
  function of the thymus in tumor-bearing hosts.

Institutional address:
     Biomedical Research Laboratories
     Kureha Chemical Industries Co.
     Ltd.
     Tokyo.


*****INTERNATIONAL JOURNAL OF IMMUNOPHARMACOLOGY*****

(REFERENCE 25 OF 41)
89213090

Toge T  Yamaguchi Y  Kegoya Y  Baba N  Yanagawa E  Hattori T
Blocking of lymphocyte surface binding sites for the soluble
  suppressor factor by protein-bound polysaccharide, PSK.

In: Int J Immunopharmacol (1989) 11(1):9-12

The ability of protein-bound polysaccharide (PSK) to block the
  suppressive activity of soluble suppressor factor (SSF) was
  investigated. The suppressive activity of SSF derived from U-937
  cells on phytohemagglutinin (PHA)-induced lymphocyte proliferative
  (LP) response was significantly reduced in the presence of PSK. The
  release of SSF was not inhibited by the treatment of U-937 cells with
  PSK. The suppressive activity of SSF on LP response to PHA was
  significantly decreased by the pretreatment of responder lymphocytes
  with PSK. Studies to determine lymphocyte receptor activity were
  performed. PSK competed with wheat germ agglutinin (WGA) which
  recognized the same receptor as SSF on the surface of the lymphocyte.
  Neither PSK nor serum competed with anti-CD4 monoclonal antibody.
  Thus, PSK may inhibit SSF-mediated suppression by competing for
  specific binding sites on the surface of responder lymphocytes.

Institutional address:
     Department of Surgery
     Hiroshima University
     Japan.

(REFERENCE 26 OF 41)
89007261

Ikuzawa M  Matsunaga K  Nishiyama S  Nakajima S  Kobayashi Y  Andoh T
  Kobayashi A  Ohhara M  Ohmura Y  Wada T  et al
Fate and distribution of an antitumor protein-bound polysaccharide
  PSK (Krestin).

In: Int J Immunopharmacol (1988) 10(4):415-23

The fate of 14C-labelled PSK in the body was investigated. Although
  only substances with low mol. wt were observed in blood shortly after
  the administration, with time, substances with high mol. wt appeared,
  suggesting absorption of PSK in its original form from the digestive
  tract. 14C-labelled PSK was distributed in bone marrow, salivary
  gland, brain liver, spleen, pancreas and tumor. Approximately 70% of
  14C-labelled PSK was excreted by expiratory air after 24 h and
  approximately 15-20% in urine after 72 h. Only a small amount of 14C-
  labelled PSK was transferred into lymph and bile. The present study
  on the in vivo behavior of PSK provides an important basis for
  further analysis of its pharmacological actions.

Institutional address:
     Biomedical Research Laboratories
     Kureha Chemical Industries Co.
     Ltd.
     Tokyo
     Japan.

(REFERENCE 27 OF 41)
94237660

Yunoki S  Tanaka N  Hizuta A  Orita K
Enhancement of antitumor cytotoxicity of hepatic lymphocytes by oral
  administration of PSK.

In: Int J Immunopharmacol (1994 Feb) 16(2):123-30

We have studied the effects of oral administration of a biological
  response modifier (BRM), PSK, on hepatic lymphocytes. Many PSK
  positive cells were observed in the liver by anti-PSK antibody
  staining. Flow cytometric analysis revealed an increase in the number
  of OX8 (CD8) positive cells in the non-parenchymal nonadherent liver
  cells (NPNALCs) which were isolated from the liver enzymatically
  digested by perfusion with collagenase. NPNALCs were fractionated by
  discontinuous density gradient centrifugation, and the number and
  cytotoxic activity of these cells were examined in each fraction.
  Although the yield of lymphocytes in each fraction was not
  significantly increased by the oral administration of PSK, the
  natural killer (NK) activity was markedly enhanced in low density
  fractions. The present findings suggest that oral administration of
  PSK is effective for prevention of liver metastasis through the
  augmentation of organ-associated NK activity.

Institutional address:
     First Department of Surgery
     Okayama University Medical School
     Japan.

(REFERENCE 28 OF 41)
94011589

Hirai R  Oguchi Y  Sugita N  Matsunaga K  Nomoto K
Enhancement of T-cell proliferation by PSK.

In: Int J Immunopharmacol (1993 Aug) 15(6):745-50

Protein-bound polysaccharide, PSK, is a biological response modifier
  and influences various immunological functions in vivo, including
  those of T-cells. However, PSK has not been proved to stimulate
  proliferation of T-cells in vitro in contrast to various lines of
  evidence that indicate the proliferation of B-cells in vitro. PSK
  enhanced the proliferation of spleen cells in C3H/He and nude mice in
  vitro. In this study such proliferating cells were detected by
  monoclonal antibody to bromodeoxyuridine (BrdU) incorporated into
  DNA, and their subsets were determined by flowcytometry with
  monoclonal antibody to Thy1 as a cell surface marker of T-cells. When
  spleen cells from C3H/He mice were cultured with PSK for 3 days, the
  percentage of BrdU positive cells increased, and about 67% of BrdU
  positive cells were Thy1.2 positive. In addition, PSK also had the
  activity to enhance the proliferation in a T-cell-enriched fraction
  from spleen cells by nylon fiber columns as well as that in original
  spleen cells. These results suggest that PSK enhances the
  proliferation of T-cells as well as B-cells.

Institutional address:
     Biomedical Research Laboratories
     Kureha Chemical Industry Co.
     Tokyo
     Japan.


*****JOURNAL OF CLINICAL AND LABORATORY IMMUNOLOGY*****

(REFERENCE 29 OF 41)
88141253

Oguchi Y  Morita I  Fujii T  Matsunaga K  Yoshikumi C  Kawai Y  Tsuru S
  Nomoto K
Involution of the thymus in tumor-bearing mice and its restoration by
  PSK. II. Mechanism of the involution and its restoration.

In: J Clin Lab Immunol (1987 Oct) 24(2):93-9

In C3H/He mice, the weight and cell number of the thymus were reduced
  and the size distribution (scatter profile measured by flow
  cytometer) of the thymus cells was changed 1 week after subcutaneous
  inoculation of X5563 plasmacytoma. This involution and change were
  prevented by intraperitoneal or oral administration of PSK. We
  examined the mechanism of this involution and change in thymus and
  the effect of PSK on them. In X5563-bearing C3H/He mice, 3H-thymidine
  incorporation into the thymus was reduced compared with that in
  control mice, as evaluated not only per organ but also per 1 mg of
  thymus tissue. Such reduction was inhibited by PSK. The substance (IS
  substance) which possessed a suppressive activity against mitogen
  induced lymphocyte proliferation, was partially purified from the
  ascites of X5563-bearing mice by the combination of ammonium sulfate
  precipitation and Sephacryl S-200 chromatography. IS substance was
  demonstrated to suppress the antibody response and delayed type foot-
  pad response against sheep red blood cells in mice. The reduction of
  weight and cell number and the change of scatter profile in thymus
  were caused by injection of this substance even in tumor-free mice.
  The restorative effects of PSK were observed also in IS substance
  injected mice. These results suggested that the various changes in
  the thymus observed in tumor-bearing mice might be attributable to
  the suppression of cell proliferation in the thymus, that such
  suppression was caused at least partly by an immunosuppressive
  substance which possessed inhibitory activity against lymphocyte
  proliferation, and that PSK had an antagonistic activity against such
  a substance so as to restore the function of the thymus in tumor-
  bearing hosts.

Institutional address:
     Biomedical Research Laboratories
     Kureha Chemical Industries Co.
     Ltd.
     Tokyo
     Japan.


*****JOURNAL OF DERMATOLOGY*****

(REFERENCE 30 OF 41)
88088208

Watanabe T  Saito H
Effects of PSK ointment and OK-432 ointment of Pseudomonas burn wound
  infection in mice.

In: J Dermatol (1987 Aug) 14(4):346-51

[No Abstract Available]


*****JOURNAL OF UROLOGY*****

(REFERENCE 31 OF 41)
93059776

Mizutani Y  Nio Y  Yoshida O
Effect of PSK and its subfractions on peripheral blood lymphocytes
  mediated cytotoxicity against urinary bladder tumor cells.

In: J Urol (1992 Nov) 148(5):1571-6

Our previous studies have indicated that the protein-bound
  polysaccharide Kreha (PSK) enhances the cytotoxic activity of
  peripheral blood lymphocytes (PBL) against the T24 human urinary
  bladder tumor cell line in patients with bladder tumor. Since PSK
  consists of a mixture of various kinds of protein-bound
  polysaccharides, the present study was designed to examine which
  subfractions of PSK mediated the enhancement of cytotoxicity. When
  PSK was separated according to size, treatment of PBL with the 50
  kilodalton (kd) or less fraction killed T24 cells more efficiently
  than unfractionated PSK-treated PBL. The higher molecular weight
  fractions did not enhance killing above the control level. PSK was
  fractionated on a diethylaminoethyl (DEAE)-cellulose column to obtain
  a protein rich fraction that absorbed onto the column and a
  polysaccharide rich fraction that did not. PBL treated with the
  polysaccharide rich fraction were able to kill T24 cells more
  effectively than unfractionated PSK-treated PBL. The protein rich
  fraction had no effect on the killing. Further fractionation of the
  polysaccharide rich fraction was performed by differential
  precipitation with ammonium sulfate. PBL treated with the
  precipitated fraction at 70-80% saturation (PSK Fraction D) enhanced
  cytotoxicity equal to that of the polysaccharide rich fraction.
  Treatment of PBL with the other fractions did not augment the
  cytotoxicity. These enhancement by PSK fractions were observed in
  healthy donors and also in patients with bladder tumor. An increase
  of the proliferative response of PBL to PSK Fraction D as well as
  unfractionated PSK was observed. Treatment of PBL with PSK Fraction D
  had no effect on the proportion of PBL binding to T24 cells, thus
  suggesting a post-binding effect. The structure of PSK Fraction D as
  inferred from the results of methylation analysis was mainly an alpha-
  glucan. These results demonstrate that PSK mediated enhancement of
  cytotoxicity and proliferation of PBL may be largely due to an alpha-
  glucan of less than 50 kd.

Institutional address:
     Department of Urology
     Faculty of Medicine
     Kyoto University
     Japan.


*****JAPANESE JOURNAL OF CLINICAL ONCOLOGY*****

(REFERENCE 32 OF 41)
92318463

Sakamaki S  Kohgo Y  Nojiri S  Kanisawa Y  Ito Y  Takahashi M  Ueno Y
  Hirayama Y  Niitsu Y
Effect of Krestin (PSK) on the induction of IL-2 activated killer
  cells.

In: Jpn J Clin Oncol (1992 Apr) 22(2):79-83

The effects of Krestin (PSK) on the generation of lymphokine-
  activated killer (LAK) cells were examined in tumor-bearing mice.
  BALB/c mice were inoculated subcutaneously with methylcholanthrene-
  induced fibrosarcoma (Meth A) cells, and PSK was administered
  intraperitoneally every other day. The reduced LAK activity in tumor-
  bearing mice was restored by the administration of PSK. Since
  involvement of the humoral immunosuppressive factor in the impairment
  of LAK activity has been suggested, the effect of PSK on the impaired
  LAK activity in the presence of an immunosuppressive factor isolated
  from the ascites of X5563 (plasmacytoma)-inoculated mice was
  examined. The activity reduced by the immunosuppressive factor in an
  in vitro induction of LAK was restored by incubation with PSK. The
  antimetastatic effect of IL-2 was also augmented by its combined use
  with PSK. The data provide a rational basis for using PSK in
  combination with recombinant IL-2 in cancer immunotherapy.

Institutional address:
     Department of Internal Medicine (Section 4)
     Sapporo Medical College.


*****NIPPON GAN CHIRYO GAKKAI SHI.  JOURNAL OF JAPAN SOCIETY FOR CANCER*****

(REFERENCE 33 OF 41)
82602506

Ogawa Y  Kimura S  Imajo Y  Hamada F  Inomata T  Ichiyanagi A  Miyaji C
  Imanaka K  Oshitani T  Takashima H  Ohbayashi K  Takada Y  Kono M
[CLINICAL SIGNIFICANCE OF CONCOMITANT USE OF PSK IN 121 CASES OF
  PRIMARY LUNG CANCER (STAGE III AND IV) TREATED WITH COMBINATIONS OF
  RADIOTHERAPY AND CHEMOTHERAPY]

In: Nippon Gan Chiryo Gakkai Shi (1981) 16(4):713-723
  (Published in Japanese)

Effects of polysaccharide-Kureha (PSK) were studied in 121 patients
  (100 men, 21 women) with primary lung cancer that was also treated
  with surgery, radiotherapy, and/or chemotherapy. The PSK (3.0 g/day x
  3 days, po) was administered at the same time as other initial
  therapies. Chemotherapeutic agents included bleomycin, mitomycin C, 5-
  fluorouracil, and urokinase. With respect to immunotherapy, the PSK
  was administered alone to 37 patients, PSK + picibanil (OK-432) were
  administered to 20, and no immunotherapy was administered to 64.
  Among the patients with Stage III lung cancer, 12-mo survival rates
  were significantly higher, and 50% survival period was 2x higher, in
  the patients given PSK + OK-432 than in those given no immunotherapy.
  Among the patients with Stage IV lung cancer, 50% survival periods
  and crude survival rates were better in patients given immunotherapy
  than in those not given immunotherapy, but significant differences
  were not observed due to severity of the disease and incomplete
  radiotherapy in the patients not given immunotherapy. Similar results
  were observed between the patients given immunotherapy and those not
  given immunotherapy when the tumors were analyzed according to
  histological types, but the differences were decreased mo 20 after
  treatment. (27 Refs)

Institutional address:
     Dept. Radiology
     Kobe Univ. Sch. Medicine
     Kobe
     Japan


*****NIPPON KETSUEKI GAKKAI ZASSHI.  ACTA HAEMATOLOGICA JAPONICA*****

(REFERENCE 34 OF 41)
90143619

Tsuji K  Takagi M  Kobayashi T  Ishiguro A  Naganuma K  Koike K
  Nakahata T  Akabane T
[Effect of a protein-bound polysaccharide, PSK, on human hemopoietic
  progenitors]

In: Nippon Ketsueki Gakkai Zasshi (1989 May) 52(3):594-600
  (Published in Japanese)

Using in vitro clonal culture assays, we investigated the effects of
  PSK, a protein-bound polysaccharide derived from the cultured
  mycelium of CM101, Coriolus versicolor (Fr.) Quel in Basidiomycetes,
  on human hemopoietic progenitors. PSK alone did not stimulate colony
  formation by human bone marrow progenitors. Although 1-100
  micrograms/ml of PSK had no effects on colony formation stimulated by
  erythropoietin and medium conditioned by phytohemagglutinin-
  stimulated leukocytes, more than 1 mg/ml of PSK inhibited all types
  of colony formation. In contrast, medium conditioned by PSK-
  stimulated leukocytes significantly stimulated formation of various
  types of colonies including erythroid bursts, granulocyte and/or
  macrophage colonies, eosinophil colonies, megakaryocyte colonies and
  mixed hemopoietic colonies. It is speculated that administration of
  the optimal dose of PSK can reduce the hematological suppression of
  antitumor drugs.


*****NIPPON RINSHO.  JAPANESE JOURNAL OF CLINICAL MEDICINE*****

(REFERENCE 35 OF 41)
82600014

Nomoto K
[POLYSACCHARIDE AND LIPOPOLYSACCHARIDE IMMUNOREGULATING MECHANISMS -
  USE OF PSK AS AN EXAMPLE]

In: Nippon Rinsho (1981) 39(4):110-115  (Published in Japanese)

Characteristics of the mechanism and the effect of the polysaccharide
  Kureha (PSK) were investigated as an example of immunopotentiation by
  polysaccharides and lipopolysaccharides. Administration of PSK (50-
  100 mg/kg ip or 1,000 mg/kg po, continuously) to sarcoma 180 or
  Ehrlich tumor-bearing ICR mice resulted in disappearance of tumors
  after transient growth of the tumor. Antitumor effects were also
  observed for various homogenic strains of methylcholanthrene-induced
  tumors. Administration of PSK in mice with sarcoma 180 tumors
  increased splenocyte cytotoxicity. PSK had an inhibiting effect on
  macrophage aggregation in normal mice, but had stimulating effect on
  macrophage aggregation in tumor-bearing mice. Ip administration of
  PSK in cancer bearing mice resulted in recovery of delayed-type foot
  pad response to sheep RBC, and po administration resulted in a
  slightly lower degree of recovery. Ip administration of PSK in
  sarcoma 180 tumor-bearing mice with decreased production of
  interferon due to poly I:C stimulation resulted in a certain degree
  of recovery of interferon production. PSK was also observed to effect
  (1) fluctuations in preventing infections due to cancer, (2) changes
  in thymus function due to cancer, (3) inhibitory effects of cancerous
  ascites, (4) fractions of immune-inhibiting factors from cancerous
  abdominal ascites, and (5) mixes of accelerating factors and
  inhibiting factors in cancerous ascites and serum. (5 Refs)

Institutional address:
     Cancer Res. Inst.
     Kyushu Univ.
     Kyushu
     Japan


*****NIPPON SANKA FUJINKA GAKKAI ZASSHI. ACTA OBSTETRICA ET GYNAECOLOGICA*****

(REFERENCE 36 OF 41)
93286457

Ishii K  Kita T  Hirata J  Tode T  Kikuchi Y  Nagata I
[Antitumor effect of PSK and its combined effect with CDDP on ovarian
  serous adenocarcinoma-bearing nude mice]

In: Nippon Sanka Fujinka Gakkai Zasshi (1993 Apr) 45(4):333-9
  (Published in Japanese)

Although the antitumor effect of PSK can be increased by potentiating
  the immune functions of PSK in tumor-bearing hosts, the mechanisms of
  its action are not fully understood. In this study, we examined the
  antitumor effect and CDDP combined effect of oral administration of
  PSK on nude mice bearing a human ovarian cancer cell line (KF cells).
  1. PSK was observed to have a significant antitumor effect in tumor-
  bearing nude mice and subsequently to bring about an increase in the
  survival rate and prolongation of the life span. 2. The antitumor
  effect of CDDP was (but not significantly) enhanced by oral
  administration of PSK and the prolongation of the life span of the
  tumor-bearing nude mice was obtained. 3. Six weeks after tumor
  inoculation, no significant natural killer (NK) cell activity in
  spleen cells from untreated nude mice was observed. However, when PSK
  (100 mg/kg but not 500 mg/kg) was given every other day, significant
  NK activity was induced. 4. The serum immunosuppressive acid protein
  (IAP) value in nude mice treated with PSK alone was significantly
  higher than that in nude mice treated with a combination of PSK (100
  mg/kg) and CDDP. These results suggest that CDDP prevents the
  increase in serum IAP that occurs when PSK is used and that
  consequently combinations of PSK and CDDP result in augmentation of
  antitumor effects.

Institutional address:
     Department of Obstetrics and Gynecology
     National Defense Medical College
     Saitama.


*****ONCOLOGY*****

(REFERENCE 37 OF 41)
94268800

Matsunaga K  Aota M  Nyunoya Y  Hakozaki M  Ishikawa Y  Ohhara M
  Sugita N  Endo H
Antitumor effect of biological response modifier, PSK, on C57BL/6
  mice with syngeneic melanoma B16 and its mode of action.

In: Oncology (1994 Jul-Aug) 51(4):303-8

The effects of PSK, a protein-bound polysaccharide, on the survival
  period and effector cell activity were examined using C57BL/6 mice
  with melanoma B16. PSK prolonged the survival period of the mice with
  tumors in a schedule- and dose-dependent manner. However, no life-
  prolonging effect was observed when carrageenan-treated mice or
  congenitally athymic mice were used as hosts. PSK enhanced the
  cytostatic activity and interleukin-1-producing capacity of
  peritoneal exudate plastic-adherent cells in C57BL/6 mice with
  tumors. These findings suggested that PSK prolongs the survival
  period of mice with B16 tumors through T-cell- and macrophage-
  dependent mechanisms.

Institutional address:
     Biomedical Research Laboratories
     Kureha Chemical Industry Co.
     Tokyo
     Japan.

(REFERENCE 38 OF 41)
94255178

Ueno Y  Kohgo Y  Sakamaki S  Itoh Y  Takahashi M  Hirayama Y  Niitsu Y
Immunochemotherapy in B-16-melanoma-cell-transplanted mice with
  combinations of interleukin-2, cyclophosphamide, and PSK.

In: Oncology (1994 May-Jun) 51(3):296-302

The effect of combination immunochemotherapy using interleukin-2 (IL-
  2), PSK and cyclophosphamide (CY) was evaluated in a pulmonary
  metastasis model in BDF1 mice. B-16 melanoma cells were inoculated
  into a hind limb. On day 3 after inoculation, 20 mg/kg of CY was
  administered intraperitoneally, and IL-2 (3.75 x 10(4) BRM
  units/head) was injected into the tail vein on days 7, 8 and 9. PSK
  (1,000 mg/kg) was administered orally every day from day 1 to day 10
  using a stomach tube. This treatment cycle was repeated three times.
  Using this combination therapy, the cytotoxicity of lymphokine-
  activated killer cells and tumor-infiltrating lymphocytes was
  enhanced. Pulmonary metastasis was remarkably suppressed and a
  prolongation of survival was obtained compared with the nontreated
  group and an IL-2+CY group. The effect was augmented by repeating the
  therapy protocol. By analyzing the killer activity and surface
  markers of tumor-infiltrating lymphocytes, it was recognized that
  increased numbers of Lyt-2-positive T cells with augmented
  cytotoxicity were obtained. This treatment modality should have
  clinical significance.

Institutional address:
     Department of Internal Medicine (Section 4)
     Sapporo Medical University School of Medicine
     Japan.


*****PROCEEDINGS, ANNUAL MEETING OF THE AMERICAN SOCIETY OF CLINICAL*****

(REFERENCE 39 OF 41)
93694949

Nakazato H  Koike A  Saji S  Ogawa N  Sakamoto J
A randomized clinical trial on adjuvant immunochemotherapy with
  protein bound polysaccharide (PSK) in gastric cancer with curative
  resection (Meeting abstract).

In: Proc Annu Meet Am Soc Clin Oncol (1993) 12:A550

A randomized clinical trial was conducted by 46 participating
  institutions from July 1985 to June 1987 in Chubu district to
  evaluate the effect of biological response modifier PSK in curatively
  resected advanced gastric cancer. After stratifying by serosal
  invasion (T2, T3), 253 patients (pts) were randomly allocated into
  the 5-fluorouracil (5-FU) and PSK group (Group P, n=124) and 5-FU
  alone group (Group C, n=129). Bolus injections of mitomycin C (MMC) 6
  mg/m2 were given to all pts on the first and seventh postoperative
  days. At 2 wk after surgery, Group P began to alternately receive PSK
  3 g/day for 4 wk and oral 5-FU 150 mg/day for 4 wk as 1 course: 10
  courses were given. Group C received 5-FU alone for 4 wk with an
  alternate rest interval for the same period. Pts characteristics
  (age, sex, depth of tumor invasion, degree of lymph node metastasis)
  were well balanced in the 2 groups. By June 30, 1992 the median
  follow-up was 72 mo and all pts were followed up for at least 5 yr.
  The 5-yr disease-free survival rate for Group P was 0.71 and was
  significantly superior to that of Group C, which was 0.59 (p=0.047).
  The 5-yr survival rate for Group P was 0.73 and for Group C 0.60 and
  overall survival with MMC+5-FU+PSK was also significantly superior to
  MMC+5-FU alone (p=0.044). In conclusion, addition of PSK to the
  standard MMC+5-FU regimen results in a significantly superior
  survival in pts who had undergone radical gastrectomy.

Institutional address:
     Dept. of Gastroenterological Surgery
     Aichi Cancer Center
     Nagoya
     Japan

(REFERENCE 40 OF 41)
92681197

Mitomi T  Tsuchiya S  Iijima N  Noto T  Ogawa N
A RANDOMIZED CONTROLLED STUDY ON ADJUVANT IMMUNOCHEMOTHERAPY WITH PSK
  IN CURATIVELY RESECTED COLORECTAL CANCER (MEETING ABSTRACT)

In: Proc Annu Meet Am Soc Clin Oncol (1992) 11:A466

In order to evaluate the adjuvant immunochemotherapy with PSK in
  curatively resected colorectal cancer, a randomized controlled study
  by 35 institutions in Kanagawa Prefecture was conducted. From March
  1985 to February 1987, 462 patients (pts) with colorectal cancer (any
  TN1-3M0 or T4N0M0) were assigned to one of two different regimens. Of
  these, 448 pts (97.0%) satisfied the eligibility criteria (colon, 249
  cases; rectum, 199 cases). The control group received mitomycin C
  (6.0 mg/m2) on the day and the day after the surgery, followed by 5-
  FU (200 mg/day) given orally for over 6 mo. The PSK group received
  PSK (3 g/day) po for over 3 yr, as well as mitomycin C and 5-FU as in
  the control group. In February 1991, a follow-up study of these pts
  was carried out to evaluate the survival rate for a minimum of 4 yr
  after surgery. Both treatment groups were well matched, as they had
  almost the same background factors. Disease-free rate (DFS) and
  overall survival rate (OS) of the PSK group were significantly higher
  than those of the control group (DFS: p=0.0250, OS: p=0.0296). Still
  more, concerning colon cancers, in each subgroup with positive
  preoperative CEA serum levels or Dukes' C, the PSK group showed more
  advantageous effects than those shown in the control group.

Institutional address:
     Dept. of Surgery II
     Tokai Univ.
     Japan


*****PROC ANNU MEET JPN CANCER ASSOC*****

(REFERENCE 41 OF 41)
91669458

Hirose K  Zachariae CO  Oppenheim JJ  Matsushima K
ACTIVATION OF HUMAN PERIPHERAL BLOOD MONONUCLEAR CELLS (PBMC) TO
  EXPRESS IMMUNOMODULATING CYTOKINE GENES BY PSK (MEETING ABSTRACT)

In: Proc Annu Meet Jpn Cancer Assoc (1990) 49:342

The protein-bound polysaccharide, PSK, has been used as a biological
  response modifier in treating patients with cancer (Cancer Treat Rev
  11:131-155 1984). Although the mechanism of its antitumor action is
  not well understood, PSK enhances various immune responses in vivo as
  well as in vitro. We have here examined the direct effect of PSK on
  cytokine gene expression and production in human PBMC in vitro. As
  determined by Northern blotting, PSK strongly induced gene expression
  for interleukin 1 alpha, 1 beta, 6, 8, tumor necrosis factor alpha
  and monocyte chemotactic and activating factor, but not for
  interleukin 2 and lymphotoxin. Expression of mRNA occurs in 1-6 hr
  using concentrations of 5-400 ug/ml of PSK. Furthermore, the
  production of these cytokines in response to PSK can be detected by
  ELISA or RIA. We conclude that these cytokines may mediate the
  immunoenhancing action of PSK in vivo.

Institutional address:
     Lab. of Molecular Immunoregulation
     NCI-FCRF
     Frederick
     MD 21701-1013





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