Clinical Trial – Ganoderma in Advanced Cancer


Shufeng Zhou1, Yihuai Gao2, Guoliang Chen3, Xihu Dai4, Jinxian Ye5

1Division of Pharmacology and Clinical Pharmacology, Faculty of Medical and Health Sciences, The University of Auckland, New Zealand

2Landcare Research, Private Bag 92170, Auckland, New Zealand

3ShanghaiAcademy of Agricultural Sciences, Shanghai, China

4Fuzhou General Hospital of Nanjing Military Region of the Peoples’ Liberation Army, Fuzhou, China

5Hospital of FujianUniversity of Traditional Chinese Medicine, Fuzhou, China

Abstract In vitro and animal studies have established that the polysaccharide fractions of Ganoderma lucidum. have potential anti-tumour activity and inhibitory effect on tumour metastasis. GanopolyTM (crude polysaccharide fractions extracted from G. lucidum by patented technique, friendly provided by Encore International Ltd, Auckland, NZ) has demonstrated immuno-modulating and tumour inhibitory effects in in vitro and mouse models. A clinical trial was conducted to evaluate the efficacy and safety of Ganopoly in 143 patients with advanced cancer. One hundred and forty three patients with advanced previously treated cancer were enrolled. Eligibility criteria included confirmation of diagnosis, objective measurable disease, Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, life expectancy of 12 weeks or greater, no recent or concomitant anti-cancer therapy, and informed consent. Patients underwent evaluation of the extent of disease, quality of life, hematologic, biochemical and selected immune function studies at baseline and after 6 and 12 weeks of Ganopoly therapy. Standard criteria were used to evaluate adverse events and response. Ganopoly was given orally at 600 mg three times daily. Of the 100 fully assessable patients, forty-six patients (32.2%) had progressive disease (PD) before or at the 6 week evaluation point (range, 5 days -6 weeks). Sixteen patients (11.2%) developed PD between 6 and 12 weeks of therapy. No objective (partial or complete) responses were observed, but 38 of 143 patients (26.6%) had stable disease (SD) for 12 weeks or more (range, 12 to 50 weeks). There was no significant change in the FACT-G scores in 85 assessable patients. However, palliative effects on cancer-related symptoms, such as sweating and insomnia, have been observed in many patients. In the group of patients with SD, FACT-G scores improved in 23 patients, unchanged in 5 patients, and declined in 1 patient. Within this group, the median change from the baseline score to the 6- and 12-week score was +7.6 and +10.3 score, both statistically significant (P < 0.05). No significant changes of the selected immune function parameters were observed in 75 assessable patients. However, in the group of 32 patients with SD for 12 weeks or more, Ganopoly significantly increased lymphocyte mitogenic reactivity to concanavalin A and phytohemagglutinin by 48-52% (P < 0.05) and significantly enhanced natural killer cell activity by 75% (P < 0.05). Five adverse events (grade 1) were recorded, 3 of which were gastrointestinal (nausea, 2; diarrhoea, 1). The results indicate that Ganopoly may have an adjunct role in the treatment of patients with advanced cancer, although objective responses were not observed in this study.

Key words: Ganoderma lucidum, Ganopoly, Tumour, Polysaccharide, Cytokine, Efficacy.


Ganoderma lucidum (W.Curt. :Fr.) P.Karst. has been used extensively as a traditional herbal medicine in China and other Asian countries for 2000 years (Shiao et al., 1994; Wasser and Weis, 1999). G. lucidum is mainly used as a tonic and a remedy for the treatment of a variety of diseases, including chronic hepatopathy, hypertension, hyperglycemia and cancer. A number of products from G. lucidum are sold as over-the-counter supplements throughout the world. Ikekawa et al. (1968) first reported on the anti-tumour effect of soluble extracts from G. lucidum in mice bearing transplanted sarcoma 180. Sasaki et al. (1971) subsequently confirmed that the polysaccharide (PS) fractions were responsible for the anti-tumour action of G. lucidum. In the past 30 years, a number of in vitro and animal studies have demonstrated the anti-tumour activity of G. lucidum administered by different routes at different stages of tumour growth (Miyazaki and Nishijima, 1981; Sone et al., 1985; Hwang et al., 1989; Lee et al., 1995; Wang et al., 1997). In animal models, crude or partially purified PS of G. lucidum has effectively inhibited tumour metastasis (Lee et al., 1984; Hwang et al., 1989). In addition, a crude G. lucidum PS extract increased the life span when administered alone or in combination with conventional cytotoxic agents (Furusawa et al., 1992; Lee et al., 1995).

Many cancer patients use G. lucidum products as an adjunct to or as the sole therapy in Asian countries. However, only a few open non-randomized clinical studies have been published in Chinese, and no clinical trials of G. lucidum against cancer have been reported in English peer-reviewed journals (Gao, 2000). GanopolyTM is an aqueous extract of G. lucidum by patented technique, which has been marketed as an over-the-counter product in New Zealand, Australia and Hongkong. Preliminary studies have indicated that GanopolyTM has immunomodulating effects, including activating effects of macrophages, T lymphocytes, and natural killer cells, and inhibitory effect of tumour growth in in vitro and animal studies (Gao, 2000). Therefore, we undertook this open, non-randomized clinical study of GanopolyTM as a single agent to investigate its efficacy and safety in adults with advanced solid tumor.


Patient Selection

Patients were entered onto the study from January 1997 through September 1998 if they met the following eligibility criteria and did not meet any of the exclusion criteria: (1) histologically confirmed, advanced-stage (staged III to IV) cancers of the lung, breast, liver, colorectum, prostate, bladder, and brain and non-Hodgkin*s lymphoma, (2) the * 4 weeks of interval between prior anticancer therapy and entry and an interval of 45 days from prior cranial radiation therapy before enrolment for patients with primary brain tumours, (3) an Eastern Cooperative Oncology Group (ECOG) performances status of 0-2 and a projected life expectancy of at least 12 weeks, (4) * 18 years, (6) adequate bone marrow function, renal function and liver function, and (7) informed consent for participation. Ethical approval was from the Institutional Research Ethics Committee. Exclusion criteria were as follow: (1) severe concurrent conditions, (2) pregnant or lactating women, (3) no objective measurable disease by physical examination and appropriate medical imaging studies, and (4) patients who had taken or were taking Ganoderma preparations.

Treatment with Ganoderma lucidum

GanopolyTM was the only anti-cancer agent administered during the study period. Patients were treated with 600 mg, three times daily orally before meals for 12 weeks. Each capsule contained 600 mg extract of G. lucidum. GanopolyTM used in the study was generously provided to study patients by Encore International Co., Auckland, New Zealand.

Clinical Evaluation

Pre-registration evaluation included medical history and physical examination. Baseline laboratory and imaging studies included blood count and differential count, biochemistry, prothrombin time, partial thromboplastin time, and selected immune functions (mitogenic responses of peripheral blood lymphocytes to concanavalin A and phytohemagglutinin, natural-killer cell activity (Dye et al., 1991), and serum immunoglibulin). Tumour markers and medical imaging studies appropriate for the specific tumour site were obtained to document the extent of disease. Cross-dimensional diameters of all measurable lesions were determined whenever possible. Assessable but non-measurable lesions (eg, positive bone scans) were monitored. Patients were treated as inpatients or outpatients. Outpatients returned on a basis of one week for interval history, physical examination, laboratory and imaging studies, FACT-G score, evaluation of response, and documentation of adverse events. Compliance was determined by direct questioning of patients and confirmation of administration records. All patients received comprehensive medical-oncology care, including active psychosocial support and a low-fat, high-vegetable, and high-fruit diet.

WHO criteria were used to evaluate efficacy (World Health Organization, 1979), and toxicities were graded according to the Common Toxicity Criteria (Green and Weiss, 1992). A complete response (CR) was defined as the complete disappearance of all tumour masses without the appearance of any new lesions and normalisation of all clinical and laboratory signs and symptoms of active disease. A partial response (PR) was defined as a 50% or greater reduction of the products of the longest perpendicular diameters of the measured sentinel lesions without demonstrable new lesions elsewhere. Stable disease (SD) occurred when no new lesions appeared and no measurable lesions increased more than 25% in a cross-directional area. PD was defined as the appearance of new lesions and/or an increase in the cross-sectional area of any previously known lesion by greater than 25%. An adequate trial was one month. Quality of life was quantified with the previously validated Functional Assessment of Cancer Therapy-General (FACT-G) scale (Cella et al., 1993). This self-administered questionnaire evaluates social, physical, social/family, emotional, and functional well-being and professional relationships and is sensitive to clinical change. Off-study criteria were (1) progressive disease (PD), (2) the patient’s desire to withdraw, (3) non-compliance, (4) unusual or unacceptable toxicity, or (5) emerging evidence that GanopolyTM was of no benefit to patients with a similar tumour type.

Statistical Analysis

The trial was designed to enrol 15 assessable patients for each of 8 tumour types, with an initial entry of 120 patients. Further accrual would be halted if no CR or PR were observed in each specific tumour type and the therapy would be judged inactive. If one or more CRs or PRs occurred among the 15 patients, another 25 patients were to be entered. Tumour types with four or more CRs or PRs were to be targeted for further study. The planned accrual was designed to provide a 90% likelihood of rejecting treatment with a true response rate of 5% or less and a 90% probability of accepting treatment with a true response rate of 20% or more. Data compiled at baseline, 6 weeks and 12 weeks were analysed by two-way analysis of variance by ranks. Median values of quantities, such as age and days since diagnosis, were compared using Wilcoxon’s rank-sum test, and categorical values (of quantities such as primary tumour site and off-study reason) were compared using X2 tests and, for 2 * 2 table, Fisher’s exact test.


Patient Characteristics

There were 83 men and 60 women. The median age of all patients was 61 years. Ninety-three percent of the patients had stage IV disease. Twenty-seven patients were not assessable for response and toxicity because they were lost to follow-up (LTFU) or refused further therapy (RFT) before 12 weeks of treatment.


The response and disposition of patients by tumour type are listed in Table 1. Two patients withdrew due to gastrointestinal toxicity, and 3 patients died of PD while undergoing therapy. Twenty seven patients were not assessable for responses or toxicity due to LTFU or RFT. Eleven patients with SD at 6 weeks were LTFU or RFT thereafter. Of the 100 fully assessable patients, forty-six patients (32.2%) had PD before or at the 6 week evaluation point (range, 5 days -6 weeks). Sixteen patients (11.2%) developed PD between 6 and 12 weeks of therapy. No CRs or PRs were observed, but 38 of 143 patients (26.6%) had SD for 12 weeks or more (range, 12 to 50 weeks). The time to tumour progression of all study patients is shown in Figure 1. For the 38 patients with SD for 12 weeks or more, the median time to tumour progression was 26 weeks, the mean * SD was 28.1 * 10.2 weeks. The prostate-specific antigen levels in the 5 prostate cancer patients reduced significantly (P < 0.05) during SD.

Table 1. Response by tumour type.

Response/ Tumour
Off study Brain Breast Colon Liver Lung Lymph Prostate Stomach Total
PD * 12 weeks (SD) 3 6 4 2 4 2 8 9 38
PD < 12 weeks 2 3 3 2 2 2 2 16
PD * 6 weeks 4 6 6 6 7 4 7 6 46
SD at 6 weeks 1 2 2 1 2 1 1 1 11
LTFU/RFT 2 4 5 5 5 1 4 1 27
Toxicity 1 1 2
Death 1 1 1 3
Total 12 19 20 19 21 10 22 20 143

PD = Progressive disease; LTFU = lost to follow-up; RFT = refused further therapy.

Quality of life

There was no significant change in the FACT-G scores in 85 assessable patients. However, palliative effects on cancer-related symptoms, such as sweating and insomnia, have been observed in many patients. In the group of patients with SD, FACT-G scores improved in 23 patients, unchanged in 5 patients, and declined in 1 patient. Within this group, the median change from the baseline score to the 6- and 12-week score was +7.6 and +10.3 score, both statistically significant using Wilcoxon’s rank-sum test. There was no significant relationship between time to tumour progression and FACT-G scores.

Immune functions

No significant changes of the selected immune function parameters were observed in 75 assessable patients. However, in the group of 32 patients with SD for 12 weeks or more, GanopolyTM significantly increased lymphocyte mitogenic reactivity to concanavalin A and phytohemagglutinin by 48-52% (P < 0.05) and significantly enhanced natural killer cell activity by 75% (P < 0.05).

Toxicity/adverse reactions

GanopolyTM was generally well tolerated and was not associated with hematologic or biochemical toxicity. No patients developed hepatitis or abnormal liver function tests. Toxicity was generally mild (grade 1). Five episodes of toxicity were recorded, 3 of which were gastrointestinal (nausea, 2; diarrhoea, 1).


There is increasing interest in the use of complementary or alternative medicine to treat patients with advanced cancer. Complementary or alternative medicine includes 1) metabolic, pharmaceutical, herbal, or immune therapeutics; 2) dietary alterations or supplementation with high-dose multivitamins, minerals, antioxidants, or other non-nutrient agents; and 3) alternative therapists or healing methods, eg. acupuncture, hypnosis, spiritual therapy, and mind-body therapy (Vickers, 2000). There is an increasing interest in finding an anti-cancer remedy from edible mushrooms, in particular from Ganoderma species, which are highly ranked in Oriental traditional medicine. There are increasing investigations in the field of anti-tumour polysaccharides from edible mushrooms, but reliable and objective comparative data on the anti-cancer activity of G. lucidum preparations as over-the-counter nutritional supplements are not available. Recently, a Phase II trial of the herbal supplement, PC-SPES, which contained G. lucidum components, in the patients with prostate cancer has been reported (Small et al., 2000). Preliminary results have shown that PC-SPES significantly reduced the serum prostate-specific androgen (PSA) levels in all 33 androgen-dependent prostate cancer patients with a duration of >57 weeks. The toxicity was acceptable.

Preclinical studies suggested that the anti-tumour action of PS of G. lucidum was due to its biological response modifying effects (Czop and Austen, 1985; Chang, 1996). PS of G. lucidum was able to activate macrophages, T lymphocytes, and natural killer cells, and induced the production of cytokines such as tumour necrosis factor (TNFa), interleukins and interferons in in vitro and mouse models (Wang et al., 1997). These cytokines can induce apoptosis of tumour cells (Wang et al., 1997; Hu and Lin, 1999). Evidence indicates that b-D-glucans are the major anti-tumour componenta of G. lucidum PS fractions (Miyazaki and Nishijima, 1981; Usui et al., 1981; Usui et al., 1983; Sone et al., 1985; Kishida et al., 1988). b-D-glucans consist of a linear backbone of b-(1* 3)-linked D-glucopyranosyl groups with varying degrees of branching from the C6 position. There is evidence that indicates that the b-D-glucans induce biological response by binding to membrane complement receptor type three (CR3, aMb2 integrin, or CD11b/CD18) on immune effector cells such as macrophage (Konopski et al., 1994; Muller et al., 1996; Battle et al., 1998; Mueller et al., 2000). The b-D-glucan binding site (lectin site) of CR3 has been mapped to a region of CD11b located C-terminal to the I-domain and its distinct metal ion-dependent adhesion site for the many protein ligands of CR3 such as iC3b, ICAM-1 and fibrinogen (Diamond et al., 1993; Lee et al., 1995; Thornton et al., 1996). Heteropolysaccharides and glycoproteins isolated from G. lucidum demonstrated host-mediated anti-tumour activity against sarcoma 180 in mice on intraperitoneal administration (Zhang et al., 1994). Other mechanisms may also be involved in the anti-tumour activity of G. lucidum. For example, PG fractions from G. lucidum may inhibit DNA polymerase (Mizushina et al., 1998a; Mizushina et al., 1998b) or post-translational modification of oncoproteins (Lee et al., 1998). Ganoderic acids T-Z isolated from G. lucidum showed cytotoxic activity in vitro on hepatoma cells (Toth et al., 1983a; Toth et al., 1983b). In addition, the organic Germanium in G. lucidum may also contribute to its anti-tumour activity (Koepf et al., 1988; Mirabelli et al., 1989; Lim and Choi, 1991; Chiu et al., 2000).

Many herbal medicines appear to work as biological response modifiers, which have become an important complementary approach to cancer treatment in Asian countries. These are agents or approaches that modify the relationship between the host and tumour by modifying the host*s biological response to tumour cells with resultant therapeutic effects (Mihich and Fefer, 1983; Werner and Jolles, 1996). Most biological response modifiers appear to act by activating, increasing, and/or restoring the reactivity of immunological effector mechanisms that are involved in resistance to tumour growth and metastasis. The inhibition of suppressor and other mechanisms which interfere with effective host resistance to tumours and help tumour cells to grow, develop, and metastasis are the targets for many biological response modifiers. This study indicates that GanopolyTM stimulated host defense in those patients with stable disease for 12 weeks or more, providing evidence for that Ganopoly may act as a host defense potentiator.

However, clinical trials with many synthetic and natural biological response modifiers, e.g. flavone-8-acetic acid and shark cartilage, have not shown any anti-cancer effects in patients (Kerr and Kaye, 1989; Miller et al., 1998). None of the 143 patients entered onto our study achieved a CR or PR, indicating that G. lucidum has not demonstrated significant anti-cancer efficacy. But G. lucidum has shown significant improvement in some cancer patients entered on this study, in terms of other end points, such as time to tumour progression, duration of SD, and quality of life. These end point parameters have been accepted in a novel paradigm to evaluate the salutary effects of investigational anti-cancer agents, in particularly those from natural sources, in patients with advanced-stage cancer. As many natural biological response modifiers have shown beneficial effects when they are used as adjuvant therapy to standard modules (Cassileth, 2000; Jacobson et al., 2000), an adjuvant role should be expected for G. lucidum in the treatment of cancer. With increasing understanding, evidence-based incorporation of traditional herbs as complementary medicine into mainstream medical science can be achieved in the near future.


Battle J, Ha TZ, Li CF, Dellabeffa V, Rice P, Kalbfleisch J, Browder W and Williams D (1998) Ligand binding to the (1-]3)-beta-D-glucan receptor stimulates NF-kappa B activation, but not apoptosis in U937 cells. Biochem Biophys Res Commun 249: 499-504.

Cassileth BR (2000) Complementary therapies: the American experience. Supportive Care Cancer 8: 16-23.

Cella DF, Tulsky DS, Gray G, Sarafian B, Linn E, Bonomi A, Silberman M, Yellen SB, Winicour P and Brannon J (1993) The Functional Assessment of Cancer Therapy scale: development and validation of the general measure. J Clin Oncol 11: 570-579.

Chang R (1996) The central importance of the beta-glucan receptor as the basis of immunologic bioactivity of Ganoderma polysaccharides, in Reishi (Mizuno T and Kim BK eds) pp 177-179, II Yang Press, Seoul.

Chiu SW, Wang ZM, Leung TM and Moore D (2000) Nutritional value of Ganoderma extract and assessment of its genotoxicity and antigenotoxicity using comet assays of mouse lymphocytes. Food Chem Toxicol 38: 173-178.

Czop JK and Austen KF (1985) A beta-glucan inhibit able receptor on human monocytes. J Immunol 134: 2588-2593.

Diamond MS, Garcia-Aguilar J, Bickford JK, Corbi AL and Springer TA (1993) The I domain is a major recognition site on the leukocyte integrin Mac-1 (CD11b/CD18) for four distinct adhesion ligands. J Cell Biol 120: 1031-1043.

Dye JF, Somers SS and Guillou PJ (1991) Simplified quantitation of cytotoxicity by intergration of specific lysis against effector cell concentration at a constant target cell concentration and measuring the area under the curve. J Immunol Methods 138: 1-13.

Furusawa E, Chou SC, Furusawa S, Hirazum A and Dang Y (1992) Antitumor activity of Ganoderma lucidum, an edible mushroom, on intraperitoneally implanted Lewis lung carcinoma in synergenic mice. Phytother Res 6: 300-304.

Gao YH (2000) The miracle herb, scientific reports of Ganoderma. Yuanqizai Publisher, Taipei.

Green S and Weiss G (1992) Southern Oncology Group standard response criteria, endpoint definitions and toxicity criteria. Invest New Drugs 10: 239-253.

Hu YH and Lin ZH (1999) Effects of polysaccharides isolated from mycelia of Ganoderma lucidum on HL-60 cell apoptosis. Yaoxue Xuebao -Act Pharmacol (Chinese) 34: 264-268.

Hwang SF, Liu KJ, Kuan YH, Tung KS, Su CH and Tung TC (1989) The inhibitory effect on artificial pulmonary metastasis of murine S-180 sarcoma cells by orally administered Ganoderma lucidum culture broth. J Chin Oncol Soc 5: 10-15.

Ikekawa T, Nakanishi M and Uehara N (1968) Anti-tumor action of some basidiomycetes, especially Phellinus linteus. Gann 59: 155-157.

Jacobson JS, Workman SB and Kronenberg F (2000) Research on Complementary/Alternative medicine for patients with breast cancer: a review of the biomedical literature. J Clin Oncol 18: 668-683.

Kerr DJ and Kaye SB (1989) Flavone acetic acid preclinical and clinical activity. Eur J Cancer Clin Oncol 25: 1271-1272.

Kishida E, Okuda R, Sone Y and Misaki A (1988) Fractionation structures and antitumor activities of the polysaccharides of Reishi, the fruiting body of Ganoderma lucidum. Osaka-Shiritsu Daigaku Seikatsukagakubu Kiyo 35: 1-10.

Koepf MP, Janiak C and Schumann H (1988) Antitumor properties of organometallic metallocene complexes of tin and Germanium. J Cancer Res Clin Oncol 114: 502-506.

Konopski Z, Smedsrod B, Seljelid R and Eskeland T (1994) A novel immunomodulator soluble aminated *-1,3-D-glucan: binding characteristics to mouse peritoneal macrophages. Biochim Biophys Acta – Mol Cell Res 1221: 61-65.

Lee S, Park S, Oh JW and Yang CH (1998) Natural inhibitors for protein prenyltransferase. Plant Medic 64: 303-308.

Lee SS, Chen FD, Chang SC, Wei YH, Liu I, Chen CF, Wei RD, Chen KY and Han RW (1984) In vivo anti-tumor effects of crude extracts from the mycelium of Ganoderma lucidum. J Chin Oncol Soc 5: 22-28.

Lee SS, Wei YH, Chen CF, Wang SY and Chen KY (1995) Antitumor effects of Ganoderma lucidum. J Chin Med 6: 1-12.

Lim UK and Choi KS (1991) The study of chemical components of Ganoderma lucidum. Seoul Natl University J Agric Sci 16: 109-114.

Mihich E and Fefer A (1983) Biological response modifiers: Subcommittee report. NCI Monogr.

Miller DR, Anderson GT, Stark JJ, Granick JL and Richardson D (1998) Phase I/II trial of the safety and efficacy of shark cartilage in the treatment of advanced cancer. J Clin Oncol 16: 3649-3655.

Mirabelli CK, Badger AM, Sung CP, Hillegass L, Sung CM, Johnson RK, Picker D, Schwartz D, Dorman J and Martellucci S (1989) Pharmacological activities of spirogermanium and other structurally related azaspiranes effects on tumor cell and macrophage functions. Anti-Cancer Drug Design 3: 231-242.

Miyazaki T and Nishijima M (1981) Studies on fungal polysaccharides. XXVII. Structural examination of a water-soluble, antitumor polysaccharide of Ganoderma lucidum. Chem Pharm Bull 29: 3611-3616.

Mizushina Y, Hanashima L, Yamaguchi T, Takemura M, Sugawara F, Saneyoshi M, Matsukage A, Yoshida S and Sakaguchi K (1998a) A mushroom fruiting body-inducing substance inhibits activities of replicative DNA polymerases. Biochem Biophys Res Commun 249: 17-22.

Mizushina Y, Watanabe I, Togashi H, Hanashima L, Takemura M, Ohta K, Sugawara F, Koshino H, Esumi Y, Uzawa J, Matsukage A, Yoshida S and Sakaguchi K (1998b) An ergosterol peroxide, a natural product that selectively enhances the inhibitory effect of linoleic acid on DNA polymerase beta. Biol Pharm Bull 21: 444-448.

Mueller A, Raptis J, Rice PJ, Kalbfleisch JH, Stout RD, Ensley HE, Browder W and Williams DL (2000) The influence of glucan polymer structure and solution conformation on binding to (1 -> 3)-beta-D-glucan receptors in a human monocyte-like cell line. Glycobiology 10: 339-346.

Muller A, Rice PJ, Ensley H, Coogan PS, Kalbfleisch JH, Kelley JL, Love EJ, Portera CA, Ha TZ, Browder IW and Williams DL (1996) Receptor binding and internalization of a water-soluble (1-]3)-beta-D-glucan biologic response modifier in two monocyte macrophage cell lines. J Immunol 156: 3418-3425.

Sasaki T, Arai Y, Ikekawa T, Chihara G and Fukuoka F (1971) Antitumor polysaccharides from some Polyporaceae, Ganoderma applanatum and Phellinus linteus. Chem Pharm Bull 19: 821-826.

Shiao MS, Lee KR, Lin LJ and Wang CT (1994) Natural products and biological activities of the Chinese medical fungus, Ganoderma lucidum, in Food phytochemicals for cancer prevention. II: Teas, spices, and herbs (Ho CT, Osawa T, Huang MT and Rosen RT eds) pp 342-354, American Chemical Society, Washington DC.

Small EJ, Frohlich MW, Bok R, Shinohara K, Grossfeld G, Rozenblat Z, Kelly WK, Corry M and Reese DM (2000) Prospective trial of the herbal supplement PC-SPES in patients with progressive prostate cancer. J Clin Oncol 18: 3595-3603.

Sone Y, Okuda R, Wada N, Kishida E and Misaki A (1985) Structural and anti-tumor activities of polysaccharides isolated from fruiting body and the growing culture of mycelium of Ganoderma lucidum. Agric Biol Chem 49: 2641-2653.

Thornton BP, Vetvicka V, Pitman M, Goldman RC and Ross GD (1996) Analysis of the sugar specificity and molecular location of the beta-glucan-binding lectin site of complement receptor type 3 (CD11b/CD18). J Immunol 156: 1235-1246.

Toth JO, Luu B, Beck JP and Ourisson G (1983a) Chemistry and biochemistry of oriental drugs. Part IX. Cytotoxic triterpenes from Ganoderma lucidum (Polyporaceae): structures of ganoderic acids U-Z. J Chem Res Synop 12: 299.

Toth JO, Luu B and Ourisson G (1983b) Ganoderic acid T and Z: cytotoxic triterpenes from Ganoderma lucidum (Polyporaceae). Tetrahedon Lett 24: 1081-1084.

Usui T, Iwasaki Y, Hayashi K, Mizuno T, Tanaki M, Shinkai K and Arakawa M (1981) Antitumor activity of water-soluble beta-D-glucan elaborateed by Ganoderma applanatum. Agric Biol Chem 45: 323-326.

Usui T, Iwasaki Y, Mizuno T, Tanaki M, Shinkai K and Arakawa M (1983) Isolation and characterization of antitumor active beta-D-glucans from the fruit bodies of Ganoderma applanatum. Carbohydr Res 115: 273-280.

Vickers A (2000) Recent advances: Complementary medicine. Br Med J 321: 683-686.

Wang SY, Hsu ML, Hsu HC, Tzeng CH, Lee SS, Shiao MS and Ho CK (1997) The anti-tumor effect of Ganoderma lucidum is mediated by cytokines released from activated macrophages and T lymphocytes. Int J Cancer 70: 699-705.

Wasser SP and Weis AL (1999) Therapeutic effects of substances occurring in higher basidiomycetes mushrooms: A modern perspective. Crit Rev Immunol 19: 65-96.

Werner GH and Jolles P (1996) Immunostimulating agents – what next – a review of their present and potential medical applications. Eur J Biochem 242: 1-19.

World Health Organization (1979) WHO handbook for reporting results of cancer treatment (WHO Offset Publication, no. 48). World Health Organization, Geneva.

Zhang J, Wang G, Li H, Zhuang C, Mizuno T, Ito H, Mayuzumi H, Okamoto H and Li J (1994) Antitumor active protein-containing glycans from the Chinese mushroom songshan lingzhi, Ganoderma tsugae mycelium. Biosci Biotech Biochem 58: 1202-1205.