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.
PMID: 9043766 [PubMed – indexed for MEDLINE]
U.S. National Library of Medicine
National Institutes of Health
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KW Tsang, CL Lam, C Yan, JC Mak, GC Ooi, JC HO, B Lam, R Man, JS Sham, WK Lam.
Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong SAR, China. firstname.lastname@example.org
BACKGROUND: Non-small cell lung cancer (NSCLC) is a leading cause of cancer deaths, and over 60% of patients present with advanced stages. Although polysaccharide peptides (PSP), isolated from the fungus Coriolus versicolor, have been reported to have anti-tumor effects, its clinical efficacy has not been properly evaluated. METHODS: Double-blind placebo-controlled randomized study to evaluate the effects of 28-day administration of PSP (Windsor Pharmaceutical, Hong Kong) on patients, who had completed conventional treatment for advanced NSCLC. RESULTS: Thirty-four patients, with no significant difference in their baseline demographic, clinical or tumor characteristics, or previous treatment regimes (P>0.05) were recruited into each of the PSP and control arms. After 28-day treatment, there was a significant improvement in blood leukocyte and neutrophil counts, serum IgG and IgM, and percent of body fat among the PSP, but not the control, patients (P<0.05). Although the evaluable PSP patients did not improve in NSCLC-related symptoms, there were significantly less PSP patients withdrawn due to disease progression, than their control counterparts (5.9 and 23.5%, respectively; P=0.04; OR 4.00). There was no reported adverse reaction attributable to the trial medications. CONCLUSION: PSP treatment appears to be associated with slower deterioration in patients with advanced NSCLC.
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Fisher M, Yang LX.
Radiobiology Laboratory, St. Mary’s Medical Center, California Pacific Medical Center Research Institute, San Francisco 94118, USA.
Polysaccharide-K (polysaccharide-Kureha; PSK), also known as krestin, is a unique protein-bound polysaccharide, which has been used as a chemoimmunotherapy agent in the treatment of cancer in Asia for over 30 years. PSK and Polysaccharopeptide (PSP) are both protein-bound polysaccharides which are derived from the CM-101 and COV-1 strains of the fungus Coriolus versicolor by Japanese and Chinese researchers, respectively. Both polysaccharide preparations have documented anticancer activity in vitro, in vivo and in human clinical trials, though PSK has been researched longer and has therefore undergone more thorough laboratory, animal and clinical testing. Several randomized clinical trials have demonstrated that PSK has great potential as an adjuvant cancer therapy agent, with positive results seen in the adjuvant treatment of gastric, esophageal, colorectal, breast and lung cancers. These studies have suggested the efficacy of PSK as an immunotherapy or biological response modifier (BRM). BRMs potentially have the ability to improve the “host versus tumor response,” thereby increasing the ability of the host to defend itself from tumor progression. The mechanisms of biological response modification by PSK have yet to be clearly and completely elucidated. Some studies suggest that PSK may act to increase leukocyte activation and response through up-regulation of key cytokines. Indeed, natural killer (NK) and lymphocyte-activated killer (LAK) cell activation has been demonstrated in vivo and in vitro, and recent genetic studies reveal increased expression of key immune cytokines in response to treatment with PSK. An antimetastatic action of PSK has also been demonstrated and is perhaps attributed to its potential to inhibit metalloproteinases and other enzymes involved in metastatic activity. PSK has also been shown to cause differentiation of leukemic cells in vitro, and this effect has been attributed to induction of differentiation cytokines. PSK has further been shown to have antioxidant capacity which may allow it to play a role as a normal tissue chemo- and radio-protector when used in combination with adjuvant or definitive chemotherapy and/or radiotherapy in the treatment of cancer, while it may also enable it to defend the host from oxidative stress. Interestingly, studies have also shown that PSK may actually inhibit carcinogenesis by inhibiting the action of various carcinogens on vulnerable cell lines. This action of PSK may play a role in preventing second primary tumors when an inducing agent, such as tobacco or asbestos, is suspected and may also prevent second malignancies due to the carcinogenic effects of radiotherapy and cytotoxic chemotherapy. Another very important aspect of chemoimmunotherapy, in general is that it may be used on debilitated patients such as those with AIDS and the elderly who might otherwise be denied potentially helpful adjuvant cytotoxic chemotherapy. Further determination of the mechanisms of these anti-cancer, immunostimulating and biological response modifying effects of PSK as well as of other protein-bound polysaccharides is certainly warranted. Indeed, with modern cellular and molecular biology techniques, a better understanding of the specific molecular effects of PSK on tumor cells as well as leukocytes may be determined. Much of the research that has been done on PSK is outlined in this paper and may serve as a foundation toward determining the mechanisms of action of this and other protein-bound polysaccharides in the treatment of cancer. This information may open new doors in the development of novel strategies for the treatment of malignancies using adjuvant immunotherapy in combination with surgery, chemotherapy and/or radiotherapy.
PMID: 12168863 [PubMed – indexed for MEDLINE]
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The multiple and complex mechanisms of action of Coriolus Versicolor PSP have been demonstrated through in vitro and animal studies. Coriolus PSP has suppressed the growth of human cancer cell lines in mice (sarcoma 180, lung adenocarcinoma and Lewis lung cancer).
It has also inhibited incorporation of two structural units of DNA (uridine and thymidine) in Ehrlich ascites tumor cells, inhibited the growth of P388 leukemia cells, and demonstrated anti-proliferative activity against cell lines of human gastric cancer, lung cancer, lymphoma, and mononuclear leukemia.
Coriolus PSP has reversed tumor-induced immunodeficiencies in sarcoma-bearing mice by increasing immunoglobulin G and C3 complement levels9. It has also been associated with increases in white blood cell count, serum IgG, CD4, CD8, B-lymphocytes, and neutrophils, along with a higher survival rate of tumor bearing mice3. Many of these effects have been attributed to PSP being a strong scavenger of superoxide and hydroxyl radicals. Coriolus Versicolor PSP has also been found to restrict the cell cycle of HL-60 leukemic cells through apoptosis.
These and other immune effects of PSK and PSP are described in reviews by Fisher and Yang, Ooi and Liu and Chu, Ho and Chow.
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