Archive for the Oesophageal 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.)

Coriolus Versicolor PSP Clinical Trials

PSP and clinical trials

While PSK has been almost exclusively developed and tested within Japan, PSP in contrast is a product of China and continues to be assessed for efficacy safety by their scientists and oncologists.  There is a close similarity between PSK and PSP polypeptides although PSP lacks fucose and instead contains arabinose and rhamnose.  Since the first development of PSP in 1983 there has been rapid progress through human clinical trials.  Phase I clinical trials were carried out by Xu (1993) and it was shown that an oral dose of up to 6g/day was well talented and lacking in side-effects.  Patients showed improvement in appetite and general condition, together with a stabilisation of haematopoietic parameters.

The Phase II study by the Shanghai PSP Research Group with 8 hospitals in Shanghai was carried out using patients with cancers of the stomach, lung and oesophagus. The dosage was 1g three times daily to a total of 190g.  Results confirmed the role of PSP as a biological response modifer improving the immunological status of the patients after surgery, radiotherapy and/or chemotherapy (Liu and Zhou, 1993).  Following the success of the Phase II clinical trials, a Phase III trial was conducted in a large cohort of patients (650) in Shanghai hospitals.  189 were randomised to taking PSP and placebo;  461 patients were unblinded to their therapy (Liu et al., 1999).  These trials showed that PSP improved disease-free survival of gastric, oesophageal and non-small-cell lung cancers while again substantially reducing the normal unpleasant side-effects of conventional treatments (Sun and Zhu, 1999; Sun et al., 1999).  PSP had a protective effect on the immunological functions of conventionally-treated patients, thus demonstrating that PSP can be classified as a clinical biological response modifier.  Other BRMs such as LAK cells, IL-2, α y IFN or TNF are also being used in the treatment of advanced cancer cases (Liu, 1999).  Yet, these drugs at effective doses, in many cases, produce quite severe side-effects such as fevers, chills, rashes, arthralgia, hypotension, oliguria, pulmonary oedema, congestive heart failure and CNS toxicities.  Mao et al. (1998) have shown dramatic anti-tumour effects when PSP was combined with IL-2.  As side-effects of IL-2 are dosage and schedule dependent, it isreasonable to expect that with PSP, a lower dose of IL-2 could be used clinically withsubsequent decrease in the severity of the side-effects (McCune and Chang, 1993).

A further observation noted that PSP in combination with radiotherapy induced a significant increase in the percentage of apoptotic cells at 24h, compared with radiation alone, and it has been surmised that the antitumour mechanism of PSPaction may also involve the induction of DNA damage by apoptosis in the target cancer cells (Stephens et al., 1991). A common adverse reaction of radiotherapy and chemotherapy is haematopoietic toxicity.  Several studies have shown a strong amelioration of thesetoxic effects by PSP (Shiu et al., 1992; Sun et al., 1999).

In a double-blind Phase II trial in Shanghai hospitals almost 300 patients suffering from gastric, oesophageal or lung cancer  were treated with conventional radiotherapy and/or chemotherapy together with PSP or shark liver oil (batyl alcohol).  Quality of life was assessed by marked improvement of clinical symptoms as well as improvements in blood profiles and/or immune indices and significant improvement in Karnovsky performance status or body weight.   PSP improved overall clinical symptoms, together with most symptoms associated with cancer therapy.  PSP was found to be effective for 82% of the patients compared with 48%for batyl alcohol (Liu and Zhou, 1993).

Many Phase III clinical trials of PSP combined with conventional therapies have demonstrated significant benefits against cancers of the stomach, oesophagus and lung (Jong and Yang, 1999; Yang, 1999).  Most studies with PSP have not fullyexplored the long-term survival benefit although in an open-label, randomised trial in oesophageal cancer has shown that PSP did significantly improve one-year and three-year survival (Yao, 1999).  Liu (1999) has commented on the favourable action of PSP in patients receiving bone autologous marrow transplants.

The corpus of laboratory and clinical evidence that PSP offers considerable benefits to patients suffering from cancers of the stomach, oesophagus and lung have led to the Chinese Ministry of Public Health granting it a regulatory license.

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

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