Tumor growth promoting activity of an immunosuppressive substance and its modulation by protein-bound polysaccharide PSK

Masahiko Fujii, Takayoshi Fujii, Ken Saito, Norio Takahashi, Chikao Yoshikumi, Junji Kakuchi and Yoshio Kawai Biomedical Research Laboratories, Kureha Chemical Industry Co., Tokyo, Japan

The administration of PSK caused the mean tumor size to decrease slightly and the duration of survival to be prolonged in comparison with control group. In tumor-bearing animals treated with IS, the administration of PSK significantly decreased the tumor size and prolonged the survival rate.

Further studies are required to clarify the origin of IS and its function in the body. For that purpose, the experimental model used in the present study is useful. Serum levels of IS may serve as a parameter to monitor the efficacy of immunotherapy

cont. in link…

(Click Here for Detail)

The Preliminary Appraisal of Polysaccharide Peptide (PSP) in Malignant and Non-malignant Diseases

Z.Y. Sun et al Shanghai Medical University

Abstract

28 late cases of malignancy of all pathologically proven were evaluated. Among them are one case of melanoma, two cases of non-Hodgkin lymphoma (NHL), twenty cases of gastro-intestinal cancers, three cases of bronchogenic carcinoma, one case each of primary hepatocellular carcinoma and multiple peritoneal malignancies of unknown origin respectively.

Most of the cases had surgery, irradiation or anticancer chemotherapy in combination. PSP were taken orally in capsules, total dose ranged from 20g to more than 800g.

A case of malignant melanoma of back was operated for five times, she was operated for the first time in Jan 1982, lymphadenopathy of right iliac and inguired glands began, consequently wide dissections of the involved nodes were done. In August 1983, the disease metastatized to right chest wall and st. axillary glands and resected specimen showed one of three subseapular nodes and one of the eight axillary nodes were metastatic melanoma lesions, the estrogen receptor content of the specimen was 125F mol/mg. On September 10, the same year a total hysterectomy was done. She received 7 courses of CCNU, PCZ and VCR regime beginning from October 1983. Despite the stable condition of her disease, she had to give up further chemotherapy on account of distinct leucopenia. In April 1985, she was found to have GI bleeding, GI bladder, condition improved after Tamoxifen and symphomate treatments. Half year later melana reappeared and right hemicolectomy and partial resection of the jijunum were done. PSP was given postoperatively, and there was no chemotherapy for already more than 2 years. She is apparently well and can participate ordinary heavy work without difficulty.

Another case of multiple peritoneal metastasis of unknown origin was benefited by PSP also. She had mass of 5x5cm in RLQ of abdomen and quite massive ascites. Ager 100g

of PSP, ascites disappeared and the mass decreased to 3x3cm. White count went up to 5200 from 3800, lymphocytic mitosis increased from 28 to 36%.

Two cases of NHL were apparently benefited too by PSP in spite of the fact one each had received systemic chemotherapy and radiotherapy of waldegers ring respectively.

All the 28 cases except 2, the general conclitims of patients and appetite improved 2/3 of the cases showed an increase of white count of 1000 at least. Around half of the patients had an increased of function of cellular immunity. One case of liver cancer showed marked amelioration of abdominal pain 80 that he could abandon dolantin injection and one case of lung cancer had conspicuous decrease of the malignant pleural effusion.

Five cases of chronic gastrites and three cases of chronic active hepatitis showed remarkable improvement in symptoms and liver function test. HBsAg declined in two of three hepatitis patients.

So far no adverse drug reaction has been observed, there were no impairment of liver and renal functions after the long term administration of PSP even up to years.

(Click Here for Detail)

The Comparative Analysis of the Extracts of the Mycelia and the Fruitbodies of Yun Zhi (Coriolus versicolor)

Qing-yao Yang1, Ji-nian Fang2, Xiu-ping Qian1 Xiao-tong Yang1, Ping Yuan1, Ke Mi1 and Hui-qin Feng1 1 Shanghai Teachers University 2 Institute of Materia Medica, Academia Sinica

Abstract

After Yun Zhi mycelia or fruitbodies are extracted by hot water and precipitated by alcohol, the Yun Zhi mycelium extract (MWA) or Yun Zhi fruitbody extract (FWA) is obtained. Then they are respectively developed by anthrone and phenolsulfate, and an analysis is made by means of ultraviolet/visible light spectra. The result shows that the maximum absorption wavelengths of MWA are 420 and 487nm respectively and those of FWA are 671 and 486 respectively. After the water solution of MWA is developed by ninhydrin, we see that its maximum absorption wavelength is 586nm; but there is no obvious absorption of FWA. Through a comparison of the infrared spectra of MWA and FWA, we discover that there is an obvious absorption of MWA at 1380nm, while there is no obvious absorption of FWA at that place. By phenol suplfate and Lowry methods to determine the contents of polysaccharide and protein, we find that the glucose contents of MWA and FWA are 36% and 48% respectively and the protein contents are 33% and 21% respectively. With a rotatory instrument to measure the specific rotatory power of MWA and FWA, we find that MWA is -0.04 and that of FWA is -0.69. With DEAE-cellulose for column chromatography, we find that the eluant of MWA contains 3 kinds of monosaccharide: galactose, mannose and rhamnose while that of FWA contains only 2 kinds of monosaccharide: galactose and rhamnose. The 0-2 mol of eluant of MWA contains 6 monosaccharide: glucose, mannose, arabinose, xylose and rhamnose while that of FWA contains 5 monosaccharide: glucose, mannose, arabinose, xylose and rhamnose. The main ingredient of FWA is not absorbed on DEAE-cellulose. Its molecular weight is 6200 Da, while that of MWA is absorbed on DEAE-cellulose. its molecular weight is 26000 Da.

(Click Here for Detail)

Suppression of in vivo tumor-induced angiogenesis by the protein-bound polysaccharide PSK.

U.S. National Library of Medicine

National Institutes of Health

In Vivo. 1994 Mar-Apr;8(2):247-50.

Kanoh T, Matsunaga K, Saito K, Fujii T.

Kureha Chemical Ind. Co., Ltd., Biomedical Research Laboratories, Tokyo, Japan.

Abstract

The anti-angiogenic effects of an antitumor protein-bound polysaccharide, PSK, obtained from cultured mycelia of Coriolus

versicolor in basidiomycetes were examined by the mouse dorsal air sac assay. PSK suppressed the mouse hepatoma

MH134-induced angiogenesis when assessed by morphological and biochemical examinations. This finding suggested that

the anti-metastatic effect of PSK is attributed to the suppression of tumor-induced angiogenesis.

PMID: 7522606 [PubMed – indexed for MEDLINE]

(Click Here for Detail)

Stimulation of human peripheral blood polymorphonuclear cell iodination by PSK subfractions.

Display Settings: Abstract

Anticancer Res. 1990 May-Jun;10(3):697-702.

Sakagami H, Kim F, Konno K.

First Department of Biochemistry, School of Medicine, Showa University, Tokyo, Japan.

Abstract

A protein-bound polysaccharide, PSK, extracted from the mycelium of Coriolus versicolor (Fr.) Quel, stimulated the

iodination (incorporation of radioactive iodine into an acid-insoluble fraction) of human peripheral blood polymorphonuclear

cells (PMN), human promyelocytic leukemic HL-60 cells and human myeloblastic leukemic ML-1 cells. In contrast, PSK did

not significantly increase the iodination of other cultured cell lines (U-937, THP-1, L-929, T98G, BALB 3T3). The PSK

stimulation of iodination of both PMN and HL-60 cells depended on incubation time and temperature, and was significantly

suppressed by the presence of myeloperoxidase inhibitors. Among various PSK subfractions, the highest molecular weight

fraction (MW greater than 200 kD), or the fraction precipitated at pH 4.0-4.5, stimulated the iodination most. In contrast,

natural and chemically modified glucans had little or no stimulation activity. The active PSK subfractions synergistically

enhanced TNF stimulation of PMN iodination. The data suggest the presence of some unique components in PSK which

directly stimulate the iodination of myeloperoxidase-positive cells.

PMID: 2369086 [PubMed – indexed for MEDLINE]

U.S. National Library of Medicine

National Institutes of Health

Publication Types, MeSH Terms, Substances

(Click Here for Detail)

Reversal of Inhibition of Reactive Oxygen Species Macrophages

These results suggest that the immunological functions of macrophages is related to the activity of glutathione peroxidase. The non-specific immune-polysaccharide might protect macrophages by the damage induced by reactive oxygen species by enhancing anti-oxidative capacity.

(Click Here for Detail)

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.

Display Settings: Abstract

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

Toi M, Hattori T, Akagi M, Inokuchi K, Orita K, Sugimachi K, Dohi K, Nomura Y, Monden Y, Hamada Y, et al.

Department of Surgery, Hiroshima University, Japan.

Abstract

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.

PMID: 1423177 [PubMed – indexed for MEDLINE]

U.S. National Library of Medicine

National Institutes of Health

Publication Types, MeSH Terms, Substances

(Click Here for Detail)