Archive for the Gastric Cancer Category

Effects and Mechanisms Of PSK & PSP Against Cancers

Found this recently in a French scientific reference site ( cat.inist.fr )

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 modem 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.

 

Source: International Institute of Anticancer Research, Attiki, GRECE  (1980) (Revue) 2002, vol. 22, no3, pp. 1737-1754 (174 ref.)

PSP Coriolus Extract – How It Works (Mechanism Of Action) – MD Anderson, Texas

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.

Source: (mdanderson.org)

See Also:

PSK PSP – Different Extractions of Coriolus Versicolor

Best Places to Buy Coriolus PSP

Trametes Versicolor PSK & Gastric Cancer

Numerous clinical trials have been carried out over the years with PSK derived from Trametes versicolor (Coriolus versicolor, Poyporous Versicolor, Turkey tail, Yun Zhi) and are briefly summarised below:

PSK:

There have been several decades of successful clinical trials using PSK to treat head and neck, upper GI, colo-rectal and lung cancers with some reported success in treating breast cancer as well.  Clinical trials with PSK have recently been extensively reviewed by Kidd (2000) and will be briefly summarised here.  Almost exclusively, clinical trials have been carried out in Japan.

PSK and gastric cancer:

PSK has been used as a form of immunotherapy for more gastric cancer patients than any other cancer type.  In early 1970s Kaibara’s group began trialing PSK with their existing chemotherapy regimens for stage IV disease (Kaibara et al., 1976).  After surgical resection (partial or full gastrectomies), PSK at 3g per day was added to a chemotherapy regimen of Mitomycin C and 5-fluorouracil (5-FU) (n=66). When compared with a historical control group, the 2 year survival rate was more than double, a finding that was later confirmed by Fujimoto et al. (1979) in a larger prospective study (n= 230).  Further studies by Hattori et al. (1979) (n=110) and Kodama et al. (1982) (n =450) suggested that PSK gave some protection against the immunosuppression that normally is associated with surgery and long-term chemotherapy.

One of the few double-blind randomised controlled trials (n=144) examining the role of single agent PSK found a significant increase in disease-free and overall survival.  PSK had significant effects on these patients immune systems as measured by increased delayed-type hypersensitivity on skin tests and enhanced chemotactic migration of neutrophils (Kondo and Torisu, 1985). All these studies suggest that individuals with very low immunity are less likely to benefit from PSK therapy than individuals with a reasonably competent immune system.  Other non- randomised trials in Japan have supported these findings (Mitomi and Ogoshi, 1986; Niimoto et al., 1988; Maehara et al., 1990; Nakazato et al., 1994).  Tsujitani et al. (1992) had previously observed that dendritic cells could infiltrate gastric cancers in some patients and biopsy examination correlated this dendritic infiltration of their tumours with an increase in disease-free and overall survival post-surgery.  It was concluded that patients with gastric cancer with limited dendritic cell infiltration prior to surgery when given PSK immunotherapy were more likely to have significant response.  The most recent phase III 2 arm trial of PSK in the treatment of gastric cancer carried out by the “Study Group of Immunochemotherapy with PSK for Gastric Cancer of Japan” showed that combining PSK with conventional chemotherapy significantly improved disease-free and overall survival (Nakazato et al., 1994).

PSK and other cancers

In a non-controlled, retrospective analysis of combined radiation, chemotherapy and immunotherapy (using PSK or OK-32, another immuno- potentiator) with 133 patients with oesophageal cancer, there were improvements in one-year and two-year survival (Okudaira et al., 1982).  In another more recent study PSK improved overall survival in oesophageal cancer in patients with levels of pre-operative high α1-anti-chymotrypsin or sialic acid (Ogoshi et al., 1995).  In a small scale trial in Taiwan for nasopharngeal carcinoma PSK adjunct therapy had a small but significant impact on five-year survival (Go and Chung, 1989).

In a study of 185 patients with epidermoid carcinoma, adenocarcinoma or large-cell carcinoma ( IIIb) given PSK as an immune system potentiator following radiotherapy, almost four times more patients who were treated with PSK had significant improvements in disease-free survival than those not given PSK (Hayakawa et al., 1993).  PSK was clinically significant with more advanced patients with Stage III disease than Stage I and II patients.  PSK had greater activity for older patients (> 70 years) and patients with small primary tumours. Early studies with breast cancer patients seemed to imply that long-term PSK immunotherapy in conjunction with chemotherapy could have beneficial results (Suginachi et al., 1984).  In a later much larger trial (914 patients) in-depth analysis implied that PSK significantly extended survival in ER-negative, Stage IIA patientswithout lymph node involvement (Toi et al., 1992).  However, in a further large trial, Morimoto et al. (1996) could find no statistical evidence of any benefit from PSK.

These contradictory studies may have been clarified by Yokoe et al. (1997) who compared HLA B40 antigen positive patients treated with PSK against B40 negatives.  It was found that B40-positive patients treated with PSK (3g/daily, two month course each year) in addition to chemotherapy had an improved 10 year overall survival rate compared to B-40 negative patients.  Thus, HLA B40 may be a predictive factor for PSK response.

The foregoing studies give strong indications of the potential benefits of incorporating PSK into some cancer treatments as an adjunct to radio- or chemotherapy.  Furthermore, PSK can improve immune status secondary to the side effects associated with traditional therapies.  As stated by Kidd (2000)  “after a quarter century of trials indicating PSK can improve cancer survival, the cumulative human findings amount to a recommendation for its inclusion in standard anticancer protocols. With its risk for adverse effects virtually nonexistent, PSK’s contribution to the benefit-risk profiles of these protocols can only be positive”.


Extracts taken from: THE ROLE OF POLYSACCHARIDES DERIVED FROM MEDICINAL MUSHROOMS IN CANCER (icnet.uk)

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