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Ganoderma Lucidum (Reishi mushroom) for cancer treatment
Abstract
Ganoderma lucidum is a natural medicine that is widely used and recommended by Asian physicians and naturopaths for its supporting effects on immune system. Laboratory research and a handful of preclinical trials have suggested that G. lucidum carries promising anticancer and immunomodulatory properties. The popularity of taking G. lucidum as an alternative medicine has been increasing in cancer patients. However, there is no systematic review that has been conducted to evaluate the actual benefits of G. lucidum in cancer treatment.
To evaluate the clinical effects of G. lucidum on long-term survival, tumour response, host immune functions and quality of life in cancer patients, as well as adverse events associated with its use.
The authors ran an extensive set of databases including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, NIH, AMED, CBM, CNKI, CMCC and VIP Information/Chinese Scientific Journals Database was searched for randomised controlled trials (RCTs) in October 2011. Other strategies used were scanning the references of articles retrieved, handsearching of the International Journal of Medicinal Mushrooms and contact with herbal medicine experts and manufacturers of G. lucidum.
To be eligible for being included in this review, studies had to be RCTs comparing the efficacy of G. lucidum medications to active or placebo control in patients with cancer that had been diagnosed by pathology. All types and stages of cancer were eligible for inclusion. Trials were not restricted on the basis of language.
Five RCTs met the inclusion criteria and were included in this review. Two independent review authors were assigned to assess the methodological quality of individual trials. Common primary outcomes were tumour response evaluated according to the World Health Organization (WHO) criteria, immune function parameters such as natural killer (NK)-cell activity and T-lymphocyte co-receptor subsets, and quality of life measured by the Karnofsky scale score. No trial had recorded long-term survival rates. Associated adverse events were reported in one study. A meta-analysis was performed to pool available data from the primary trials. Results were gauged using relative risks (RR) and standard mean differences (SMD) for dichotomous and continuous data respectively, with a 95% confidence interval (CI).
The methodological quality of primary studies was generally unsatisfying and the results were reported inadequately in many aspects. Additional information was not available from primary trialists. The meta-analysis results showed that patients who had been given G. lucidum alongside with chemo/radiotherapy were more likely to respond positively compared to chemo/radiotherapy alone (RR 1.50; 95% CI 0.90 to 2.51, P = 0.02). G. lucidum treatment alone did not demonstrate the same regression rate as that seen in combined therapy. The results for host immune function indicators suggested that G. lucidum simultaneously increases the percentage of CD3, CD4 and CD8 by 3.91% (95% CI 1.92% to 5.90%, P < 0.01), 3.05% (95% CI 1.00% to 5.11%, P < 0.01) and 2.02% (95% CI 0.21% to 3.84%, P = 0.03), respectively. In addition, leukocyte, NK-cell activity and CD4/CD8 ratio were marginally elevated. Four studies showed that patients in the G. lucidum group had relatively improved quality of life in comparison to controls. One study recorded minimal side effects, including nausea and insomnia. No significant haematological or hepatological toxicity was reported.
Our review did not find sufficient evidence to justify the use of G. lucidum as a first-line treatment for cancer. It remains uncertain whether G. lucidum helps prolong long-term cancer survival. However, G. lucidum could be administered as an alternative adjunct to conventional treatment in consideration of its potential of enhancing tumour response and stimulating host immunity. G. lucidum was generally well tolerated by most participants with only a scattered number of minor adverse events. No major toxicity was observed across the studies. Although there were few reports of harmful effect of G. lucidum, the use of its extract should be judicious, especially after thorough consideration of cost-benefit and patient preference. Future studies should put emphasis on the improvement in methodological quality and further clinical research on the effect of G. lucidum on cancer long-term survival are needed. An update to this review will be performed every two years.
... Apart from Kampo, natural herbs believed to have anticancer activity are quite a few. Among them, Ganoderma lucidum has an anticancer efect in vitro and in vivo, although it remains controversial [13][14][15][16]. In Japan, there is an herbal mixture named WTMCGEP that contains Ganoderma lucidum [17]. ...
... Tese fndings emphasize the pivotal role of WTMCGEP in reinforcing antitumor immunity through CD8 + T cells in a tumorbearing host on the condition that immunosuppression is partly mitigated because of defciency of NKT cells. Although six of the seven ingredients of WTMCGEP have already been known to possess some antitumor properties [13][14][15][16][18][19][20][21][22], only anecdotal evidence on the antitumor efect of this mixture itself exists. Terefore, to our best knowledge, this is the frst time when WTMCGEP's contribution to enhancing the immunological antitumor efect in vivo is shown. ...
... Although a precise mechanism is yet to be elucidated, the reduction in PMN-MDSCs in tumor-bearing WTMCGEP mice may be partially mediated by Ganoderma lucidum, which is one of the major components of this mixture. Among the seven ingredients of WTMCGEP, Ganoderma lucidum may be the most studied as an anticancer agent and is known to have anticancer efects in vitro and in vivo, controversies remain [13][14][15][16]. However, the fve remaining ingredients, other than Trapae fructus, have also been reported to have anticancer properties [18][19][20][21][22]. Terefore, WTMCGEP's antitumor efect may not depend on or may be more potent than Ganoderma lucidum alone. ...
Although Kampo—a traditional Japanese herbal medicine—contributes in the control of tumor growth in vivo in experimental animals, most of the antitumor effects are prophylactic and not therapeutic. In this study, we determined whether oral administration of an herbal mixture containing Ganoderma lucidum (WTMCGEP; Wisteria floribunda, Trapae fructus, Myristica fragrans, Coicis semen, Ganoderma lucidum, Elfvingia applanata, and Punica granatum), anecdotally used in Japan for the palliative care of patients with cancer, exhibits a therapeutic effect on tumor growth in vivo in a hypodermic murine CT26 colorectal tumor model. An in vitro tumor assay revealed that WTMCGEP extract has some direct influence over suppression of tumor growth. In wild-type BALB/c mice, WTMCGEP did not show any antitumor effect in vivo. However, in BALB-CD1d−/− mice with partly mitigated immunosuppression by reason of them being devoid of both antitumoral type I and immunosuppressive type II natural killer T (NKT) cells, WTMCGEP therapeutically suppressed tumor growth. CD8+ T cell depletion significantly accelerated tumor growth in WTMCGEP mice; therefore, its antitumor activity was primarily in a CD8+ T cell-dependent manner. Regarding immunosuppressive cells in tumor-bearing CD1d−/− mice, WTMCGEP did not influence the abundance of tumor-infiltrating CD4+ and Forkhead box protein 3+ regulatory T cells. However, it reduced both intratumoral and splenic Ly6G+ Ly6Clo polymorphonuclear myeloid-derived suppressor cells, which were most likely involved in tumor growth inhibition related to higher frequency of intratumoral CD107a+ CD8+ T cells in these mice. Overall, these data illustrate that the deficiency of NKT cells urges WTMCGEP to exert a therapeutic antitumor effect mainly through CD8+ T cells. Our efforts are the first to scientifically demonstrate the WTMCGEP’s contribution to tumor immunity.
... Ganoderma lucidum, commonly known as Lingzhi, is a traditional Chinese fungus that is widely used in China, Japan, Korea, and other Asian countries. It possesses a wide range of bioactivities, including anti-tumor properties [1,2], immunomodulatory effects [3], antimicrobial and antiviral activities [4], liver-protective effects [5], anti-aging properties [6], and potential in diabetes control [7]. Lingzhi has been extensively studied due to its numerous beneficial properties. ...
... However, Lingzhi's practical applications are hindered by its poor palatability due to its strong bitter taste. Furthermore, there have been reports of adverse reactions associated with Lingzhi consumption, such as dry mouth, nausea [12], diarrhea [13], sore throat [14], and insomnia [1]. ...
The genus Ganoderma is a widely used medicinal fungus in East Asia. The main medicinal components are triterpenoids, polyphenols, and polysaccharides. Bitterness is an important commercial trait for Ganoderma. White Lingzhi (G. leucocontextum) is less bitter. But the characteristics of its nutritional and medicinal ingredients are still unclear, which undoubtedly limits its commercialization. In this study, the medicinal ingredients of Lingzhi and white Lingzhi were extracted and quantified. The structure and antioxidant activities of purified polysaccharides were determined. At the same time, their nutritional differences were compared. White Lingzhi contains more medicinal ingredients and its polysaccharide is more active. The higher protein content may be one of the reasons for weaker bitterness in white Lingzhi. The nutritional and medicinal traits of white Lingzhi were described for the first time in this study, which provides fundamental knowledge to support the development of white Lingzhi.
... The adaptogenic properties of Reishi mushroom enable it to increase resistance to stress, thus helping the body cope better with multiple forms of stress. With the modulation of the body's stress response systems, Reishi mushroom restores physiological process balance and thereby supports mental and physical well-being [31]. ...
... In addition, Reishi mushroom is considered as an immunomodulatory potent herb, as it supports and regulates the immune system [31]. It is composed of biologically active substances such as polysaccharides, triterpenoids, and ganoderic acids, which are known to stimulate immune function and reduce inflammation [32]. ...
Adaptogenic plants are increasingly being recognized as potential therapeutic agents in the treatment of mental health disorders. In this review, we summarized current evidence of their efficacy, safety, and mechanisms of action in the treatment of mental health disorders. The findings of the clinical studies showed that adaptogens, such as ashwagandha, Rhodiola, and holy basil, are effective in alleviating the symptoms of stress, anxiety, and depression, with a good safety profile and minimal side effects. Adaptogenic plants exert their effects through several mechanisms of action, including modulation of the stress response systems, neuroprotection, and anti-inflammatory effects. However, challenges remain in standardizing adaptogenic plant extracts and dosage forms and in clinical studies to analyze the interactions with other pharmaceuticals. In light of these challenges, adaptogenic plants represent a promising alternative to conventional pharmacotherapy for a wide range of mental health disorders, with probable lower side effects and greater accessibility. From a clinical practice perspective, there are promising prospects for the potential of these herbal remedies in the treatment of mental health disorders for the augmentation of treatment options and for better outcomes. Further research is warranted to optimize the therapeutic regimens and to integrate these remedies into comprehensive paradigms of mental health care.
... G. lucidum has been shown to have a wide range of anti-cancer effects which is used as an adjunctive therapy to reduce pain and improve quality of life for patients (Ahmad, 2020;Jiang, Slivova, Valachovicova, Harvey, & Sliva, 2004;L. Jin, Huang, Wu, Li, & Chen, 2016;Jin, Ruiz Beguerie, Sze, & Chan, 2016;Lu et al., 2004;Tang et al., 2020;Wu, Ye, Xu, Zhang, & Tang, 2018;Zhao & He, 2018;Zhong et al., 2023). GLSO also has various anticancer effects. ...
... GLSO has been shown to have a protective effect on liver diseases caused by various etiologies. GLSO has an auxiliary protective effect on mice with acute alcoholic liver injury induced by ethanol, reducing triglyceride (TG) and MDA production during alcohol metabolism and reducing fat deposition in the damaged liver (Jin, Huang, Wu, Li, & Chen, 2016;Jin, Ruiz Beguerie, Sze, & Chan, 2016;Zhao, Hu, Li, & Chen, 2016). A trial confirmed that GLSO not only had a protective effect against D-aminogalactose-induced liver injury in mice but also inhibited transplanted hepatocellular carcinoma (Liu, Zhong, Yuan, & Huang, 2000;. ...
Ganoderma lucidum is a Chinese medicinal fungus with a long history of use in healthcare and disease treatment. G. lucidum spores (GLS) are tiny germ cells released from the mushroom cap during the mature stage of growth. They contain all the genetic active substances of G. lucidum. G. lucidum spore oil (GLSO) is a lipid component extracted from broken-walled Ganoderma spores using supercritical CO2 extraction technology. GLSO contains fatty acids, Ganoderma triterpenes, sterols and other bioactive compounds. Previous studies have demonstrated that GLSO has a wide range of pharmacological properties, including anti-tumor, anti-aging, neuroprotection, immunomodulation, hepatoprotection and modulation of metabolic diseases. This review summarizes the research progress of GLSO over the past two decades in terms of its bioactive components, extraction and processing techniques, pharmacological effects and safety evaluation. This provides a solid foundation for further research and application of GLSO.
... Many studies on mushroom have proved that mushroom effectively cures cancer patient by reducing the survival, proliferation, and metastasis of cancer, work as an adjuvant in chemo-sensitization, and have a deleterious effect on multi-drug resistant activity and potent immunomodulatory activity. Jin et al. reported that Ganoderma lucidum mushroom administrated cancer patients live a better life than control [135]. 30 to 40% of Cancer patients are affected by sleeping disorders so much, which generate fatigue, augmented depression, higher pain, and lower survivability. ...
... Most mushrooms have the bioactive compound beta-glucan, which have also the ability of hemopoietic activity [140]. Jin et al. reported that mushroom Ganoderma lucidum with anticancer drugs had been shown to have a positive effect on cancer patients (especially lung cancer, colon cancer, and breast cancer) as compared to being treated with a placebo and chemo/radiotherapy alone [135]. ...
Mushrooms: A Wealth of Nutraceuticals and An Agent of Bioremediation informs readers about the growing role of mycotherapy and fungal biotechnology for a sustainable future. It presents reviews of efficient treatment strategies for different diseases with the help of mushrooms and derived nutraceuticals. This book also highlights efficient bioremediation strategies exhibited by common mushrooms. Starting with topics on the nutritional and medicinal values of various edible and non-edible mushrooms, the contributors explore their bioactive components. The book progressively covers the antidiabetic, anticancer and antimcrobial potential of mushrooms. The contents are rounded up by reviews of the application of fungal xylanase enzymes and bioremediation of heavy metals from the environment. This is a comprehensive reference for researchers interested in working in the field of applied mycology for nutraceuticals and environmental bioremediation for pollution control.
... Despite advancements in cancer treatment, including chemotherapy, radiotherapy, hormonal therapy, and surgery, researchers are pursuing novel bioactive compounds to treat malignancy to avoid adverse side effects. Fungal polysaccharides have shown a huge therapeutic potential in this field of clinical research (Jin et al. 2012;Aras et al. 2018;Daba et al. 2020;Din et al. 2020;He et al. 2021a, b;Xu et al. 2021;Chandrawanshi et al. 2022;Mishra and Kaladhar 2022). Polysaccharides are classified according to their structure (linear and branched), sugar composition (homo-and hetero-polysaccharides), and type of bonds between monomers, such as β-(1→3), β-(1→6), or α-(1→3), etc. Fungal polysaccharides mainly belong to β-glucans with a backbone of glucose residues linked by β-(1→3)glycosidic bonds and an attached β-(1→6) branch. ...
... Preclinical trials have suggested that G. lucidum possesses promising anticancer and immunomodulatory properties. Over 250 clinical studies on G. lucidum and other Ganoderma species have been published (Jin et al. 2012). In this study patients with G. lucidum extract in their cancer regimen were 1.27 times more likely to respond to chemotherapy or radiotherapy than those who did not. ...
Several human diseases, such as diabetes, cancer, cardiovascular and neurodegenerative disorders, increasingly affect the adult population worldwide. Therefore, scientists have tried to discover new natural sources of medicines, especially from mushrooms, to prevent and treat these diseases. Wild mushrooms and mushrooms growing on solid media or in submerged cultures belong to a large number of genera (Agaricus, Auricularia, Ganoderma, Grifola, Hericium, Lentinula, Schizophyllum) and may be used to produce biologically active compounds (lectins, polysaccharides, phenolics, terpenoids, and steroid derivatives) as anti-inflammatory, antimicrobial, antioxidant, antitumor, antiviral, hepatoprotective, hypocholesterolemic, hypoglycemic, immunomodulatory, and neuroprotective agents. Metabolomics and genomic studies of the unexplored biotechnological potential of mushrooms may also assist in the production of mushroom-derived biotech products. High-quality, long-term, randomized, double-blind, placebo-controlled clinical studies have been described as necessary to prove the efficacy of mushroom extracts or isolated compounds. The present review discusses the current state of knowledge and the main findings of previous studies on mycotherapeutics and healthy mycofood. This chapter is an update contribution to modern mycopharmacology and biomedicine. Keywords: Biomedicine Clinical trials Mushrooms Mycopharmaceuticals Mycotherapy Nutraceuticals
... Selected examples of documented benefits of some nutraceuticals are described in Table 2. A meta-analysis of 12 studies found cinnamon reduced inflammatory markers and could be used as a potential adjuvant in oxidative stress and inflammation after judicious consideration of cost-benefit and patient preference [26]. A meta-analysis of five RCTs finds that patients who had been given Ganoderma lucidum (Lingzhi mushroom) alongside chemotherapy/radiotherapy were more likely to respond positively compared to either chemotherapy or Ganoderma lucidum on their own [27]. ...
... Cinnamon [26] Systematic review and meta-analysis of 12 studies to elucidate the impact on inflammation and oxidative stress. Daily quantity taken for cinnamon was about 1.5 g-4 g Primary outcomes were different in different studies and included C-reactive protein (CRP), Malondialdehyde (MDA), total antioxidant capacity (TAC) and intracellular adhesion molecule 1 (ICAM-1). ...
Increased numbers of patients with chronic conditions use nutraceuticals or food-based therapeutics. However, to date, there is no global consensus on the regulatory processes for nutraceuticals. With the increased use, issues of quality and safety have also arisen. This review summarises the current regulations held for nutraceuticals in the USA, European and Australian jurisdictions using regulatory authority sites and databases. The efficacy and safety concerns, product development, gaps in regulation and challenges in ensuring product authenticity are also summarised. The data highlight the complexity that the globalisation of nutraceuticals brings with respect to challenges in regulation and associated claims regarding efficacy and safety. The development of an effective system with integrity is needed to increase vertical collaboration between consumers, healthcare practitioners, and government agencies and the development of international risk assessment criteria and botanical compendia. This will help in greater transparency and improved trust in the process and products. Emerging technologies could play a role in improving systems engineering by information sharing and leveraging the strengths of different countries. In conclusion, nutraceuticals have been poorly regulated leading to spurious claims based on little or no real evidence. This makes it difficult to separate meaningful results from poor data. More stringent regulation and an effective system of integrity are required to ensure efficacy and safety and enable the adequate monitoring and increase consumer and healthcare professionals’ confidence.
... More recent studies have highlighted their use in immune augmentation, chemotherapy modulation, and reduction of therapy toxicity. The most studied medicinal mushrooms used in the treatment of cancer include Reishi (Ganoderma lucidum), Turkey Tail (Trametes versicolor), and Cordyceps (Cordyceps sinensis) (Jin et al., 2012). They contain bioactive molecules such as polysaccharides, triterpenoids, and beta-glucans with immune stimulation, apoptosis-inducing, and anticancer activities (Zhao et al., 2020). ...
... Chemotherapy has been used to treat illnesses that have spread or recurred although its impact on survival is limited. There is little doubt that individuals with hematogenous metastases from cervical cancer require improved therapeutic alternatives for the treatment [219,220]. Worldwide, cisplatin-based chemotherapy is often used to treat cervical cancer [218]. According to a recent study, Ganoderma lucidium is a medicinal mushroom and its polysaccharide may have anticancer effects on cervical cancer cells [221]. ...
Worldwide, cancer is a great cause of death and a public health issue. Cancer has been the leading cause of death in developing nations for many years. Cancers are typically treated with surgery, immunotherapy, chemotherapy, and radiation therapies. However, these techniques have some undesirable side effects, including neurological illness, high toxicity levels, discomfort, and mental stress. Biologically active compounds discovered in mushrooms may be utilized to reduce ill effects and increase the efficacy of the current therapies. Mushrooms have efficient therapeutic activities such as antimicrobial, antitumor, antidiabetic, anticancer, and antioxidant activity. Bioactive compounds like polysac-charides, terpenoids, β-glucan, steroids, polyphenols, flavonoids, proteins, and peptides have precisely well-recognized anticancer activity. In this review paper, we described the biomedical activities of the mushroom against various cancers. The immune-modulating components in mushrooms activate NK cells and macrophages to target cancer cells. Due to immunomodulatory properties of mushroom-derived bioactive compounds in cancer therapy to highlight the need for further research in this area further studies needs to validate in clinical samples.
... Polysaccharides and triterpenes in medicinal mushrooms, such as ganoderic acids from Ganoderma lucidum, inhibit angiogenesis by downregulating VEGF and HIF-1α expression, thereby limiting tumor vascularization and nutrient supply [43]. Certain fungal-derived metabolites also exhibit direct apoptotic effects via mitochondrial cytochrome c release and caspase activation, modulating intrinsic apoptotic pathways in malignant cells [44]. Probiotics influence cancer progression through microbiota-host interactions that regulate immune function and metabolic homeostasis. ...
Background: The use of complementary integrative medicine (CIM) by cancer patients is currently very common. The main reasons why patients turn to CIM are to improve quality of life (QoL) and support the immune system. Unfortunately, many patients rely on CIM self-prescription, neglecting the risk of interactions with anticancer treatments (ACTs). The primary objective is to demonstrate the feasibility of combining CIM and ACT in a multidisciplinary approach to improve the QoL of cancer patients and to reduce ACT’s adverse events. Methods: Cancer patients were treated with CIM by expert physicians. CIM mainly consisted of vitamins C and D, the medicinal mushrooms blend U-CARE, and probiotics administered alone or in combination. The patients were followed-up by physicians and data were recorded in a detailed shared file. Results: A total of 54 cancer patients were treated with an integrative approach, especially during ACTs. The combination showed a good safety profile. No adverse events occurred in 92.6% of patients, whereas only 7.4% of patients experienced gastrointestinal or liver toxicity from the CIM approach. The main benefit of the CIM approach was improved fatigue and QoL, and this was mainly achieved by the concomitant use of polytherapy-based complementary medicine (PCM) and U-CARE. The toxicity improvement was mainly associated with the use of solely U-CARE. Conclusions: These results highlight the feasibility of the CIM approach in cancer patients addressed by a multidisciplinary team of experts in the field. The patient-centered and evidence-based approach of CIM is an example of the comprehensive and coordinated strategy pursued by the EU in its programmatic document against cancer aiming to focus on the QoL of patients and to avoid potentially harmful CIM self-prescription.
... Ganoderma is known as Olu iju in the yoruba speaking area of Nigeria, lingzhi in China and reishi by the Japanese (Nwakanma et al., 2021;Oke et al., 2022). Ganoderma products are popular as dietary supplements in Asia (Jin et al., 2012;Barbieri et al., 2017;Celal, 2019). The species is known to have medicinal, phytochemical, polysaccharide, and physiologically active constituents. ...
Limited efforts have been made to identify and document medicinal macrofungi flora such as Ganoderma species in Nigeria. This study investigated the heavy metal contents, antimicrobial potentials, and molecular characteristics of Ganoderma species from Lagos State, Nigeria. Samples were digested and analyzed for heavy metal contents using Atomic Absorption Spectrophotometry (AAS), while antimicrobial activity was evaluated through the agar well diffusion method. Internal transcribed spacer sequences (ITS1 and ITS4) from four isolates were analyzed using GenBank BLAST. Two species were identified as G. enigmaticum and G. mbrekobenum. Five heavy metals; lead (0.27±0.02-0.51±0.19 ppm), cadmium (6.20±4.47-9.12±1.80), chromium (0.24±0.47-0.36±0.12 ppm), nickel (5.96±0.72-7.19±1.25 ppm) and manganese (7.62±0.59-11.51±0.31 ppm) were quantified. The Ganoderma spps. exhibited inhibitory activities against Salmonella typhi, Escherichia coli, Candida albicans, Pseudomonas aeruginosa and Staphylococcus aureus at 10 mg/mL, 20 mg/mL 30 mg/mL and 40 mg/mL. The heavy metals were within safe limits established by the World Health Organization, indicating minimal health risks to the general public. The findings suggest that Ganoderma species were safe for consumption and potential sources of novel antimicrobial agents. Hence efforts should be focused on promoting the sustainable utilization of these wild mushrooms.
... The reduction of chemotherapy-related side effects such as hair loss, pain, vomiting, and nausea was observed using Ganoderma extracts (Jeitler et al. 2020). Based on the meta-analysis results by Jin et al. (2012), patients who were administrated G. lucidum in addition to chemotherapy or radiation therapy exhibited a more favourable response than with chemo/radiotherapy alone. ...
... Among them, astragalus polysaccharides exert anti-tumor effects through immune system regulation, particularly by enhancing natural killer cell activity and promoting T lymphocyte proliferation [16]. Ganoderma polysaccharides improve immune function and suppress tumor growth by inducing cell cycle arrest and promoting apoptosis through various mechanisms [17,18]. By influencing the gut microecological system and inflammatory pathways, Dioscorea opposite exhibits anti-tumor properties. ...
Integrating network pharmacological analysis and bioinformatic techniques, this study systematically investigated the molecular mechanisms of six medicinal food homologous plants (Astragalus membranaceus, Ganoderma lucidum, Dioscorea opposite, Curcuma longa, Glycyrrhiza uralensis, and Pueraria lobata) against colorectal cancer. Through screening the TCMSP database, 303 active compounds and 453 drug targets were identified. By integrating differential expression gene analysis with WGCNA on the GSE41258 dataset from the GEO database, 49 potential therapeutic targets were identified. GO and KEGG enrichment analyses demonstrated that these targets are primarily involved in drug response, fatty acid metabolism, and key cancer-related pathways. Cross-validation using three machine learning algorithms—LASSO regression, SVM-RFE, and Random Forest—pinpointed four critical target genes: CA1, CCND1, CXCL2, and EIF6. Further, CIBERSORT immune infiltration analysis revealed strong associations between these core genes and the tumor immune microenvironment in colorectal cancer patients, notably in modulating M0 macrophage infiltration and mast cell activity. Molecular docking analyses confirmed robust binding interactions between active compounds and core target proteins. This study systematically elucidated the molecular mechanisms of six medicinal food homologous plants against colorectal cancer, providing scientific evidence for their rational clinical application.
... Therefore, it can be used as an adjuvant to treat cancer while reducing the side effects of chemotherapy. Among the many biological roles played, Ganoderma polysaccharides have immunomodulatory and anti-neurodegenerative actions [16]. Specifically, β-glucans are recognized for their biological and physiological properties. ...
... Preceding research using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTIC QLQ-C30) showed that a supplement of GLBS 3 g/day for 4 weeks in breast cancer patients undergoing hormonal therapy significantly increased the quality of life with respect to the functional, emotional and cognitive domains, and the total quality of life score (Zhao et al., 2012). Jin et al. (2016) carried out a systematic review and showed that the use of GL in cancer patients had a positive impact on quality of life. This study showed no significant change in the quality of life in cancer patients who had completed chemotherapy and received GLBS for 8 weeks, in accordance with Gao et al. (2002), who reported that patients with advanced cancer receiving GL 5.4 g per day for 12 weeks had no significant change in the FACT-G score. ...
... Asian and Eastern European traditions have used medicinal mushrooms to treat ailments over centuries. They are utilized to treat infectious diseases, and cancers, supporting longevity and maintain a well-balanced, healthy lifestyle (Aung, 2005;Jin et al., 2012). Medicinal mushrooms enhance the host immune system through their bioactive compounds, such as (1,3;1,6)-b-glucans, heteroglucans, proteoglycans, lectins, phenols, sterols, triterpenes and pharmacologically relevant proteins like Ling zhi-8 (Kino et al., 1989). ...
Medicinal mushroom are known for their therapeutic capabilities and one such notable example is the Turkey tail mushroom (Trametes versicolor). This fascinating medicinal fungus, belonging to the genusTrametes
that has been in used for centuries in traditional medicine systems, particularly in Asia. Turkey tail mushroom look-alikes due to the existence of diversity and variation in species.It is crucial to observe key morphological features for proper identification of fruiting bodies. The presence of phenols, polysaccharides,
terpenoids, and other compounds in Turkey tail enrich its biological activities as a potent anticancer, antioxidant, antimicrobial, antiaging, hepatoprotective, and anti-diabeticpropeties. Recent studies have explored
the various metabolic activities of T. versicolor, highlighting important polysaccharides such as Polysaccharopeptides (PSP) and Polysaccharopeptide Krestin (PSK), which have been thoroughly researched for their
effects on cancer cells. This review attempts to disclose the importance of Turkey tail mushrooms and their untapped medicinal potential to further benefit immunology studies.
... Among the bioactive compounds in GL, triterpenoids and polysaccharides are the most pharmacologically active, showing a range of medicinal effects like antimicrobial, antitumor, anti-inflammatory, and hypolipidemic activities [259][260][261][262][263][264][265][266][267][268][269]. Modern scientific research has further underscored its immunostimulant and antioxidant properties [270]. Polysaccharides derived from GL have been particularly noted for their antioxidant capabilities [271][272][273], and triterpenoids are recognized for their complex and highly oxidized chemical structures that contribute to the mushroom's biological capacity [274,275]. ...
Chronic kidney disease (CKD) presents a substantial global public health challenge, with high morbidity and mortality. CKD patients often experience dyslipidaemia and poor glycaemic control, further exacerbating inflammation and oxidative stress in the kidney. If left untreated, these metabolic symptoms can progress to end-stage renal disease, necessitating long-term dialysis or kidney transplantation. Alleviating inflammation responses has become the standard approach in CKD management. Medications such as statins, metformin, and GLP-1 agonists, initially developed for treating metabolic dysregulation, demonstrate promising renal therapeutic benefits. The rising popularity of herbal remedies and supplements, perceived as natural antioxidants, has spurred investigations into their potential efficacy. Notably, lactoferrin, Boerhaavia diffusa, Amauroderma rugosum, and Ganoderma lucidum are known for their anti-inflammatory and antioxidant properties and may support kidney function preservation. However, the mechanisms underlying the effectiveness of Western medications and herbal remedies in alleviating inflammation and oxidative stress occurring in renal dysfunction are not completely known. This review aims to provide a comprehensive overview of CKD treatment strategies and renal function preservation and critically discusses the existing literature’s limitations whilst offering insight into the potential antioxidant effects of these interventions. This could provide a useful guide for future clinical trials and facilitate the development of effective treatment strategies for kidney functions.
... Similar species of Ganoderma have been found growing in the Amazon [2]. Ganoderma lucidum is used for cancer, aging, boosting the immune system to prevent or treat infections, and for many other reasons, but there is no good scientific evidence to support these uses [3]. ...
Introduction: Ganoderma lucidum is considered to be a medicinal mushroom, widely used to prevent or treat different types of diseases including cancer, cardiovascular disease and hepatic dysfunction. This study aimed to evaluate the effect of Ganoderma lucidum on acetaminophen-induced liver injury in wistar rats. Methods: Forty (40) male wistar rats were used for this study. Hepatoxicity was induced by oral administration of acetaminophenn (3000 mg/kg of body weight) for the last 21 consecutive days of the dietary of regimen Ganoderma lucidum. These rats were divided into eight cages each containing Five rats. Control Group 1 fed on feed and water only throughout the study, Group 2 received acetaminophen only, Group 3 received Acetaminophen + Standard drug (silymarin), Group 4 received Acetaminophen +100 mg/kg body weight of Ganoderma lucium extract, Group 5 received Acetaminophen + 200 mg/kg body weight of Ganoderma lucidum extract, Group 6 received Acetaminophen + 300 mg/kg body weight of Ganoderma lucidum extract , Group 7 received 100 mg/kg of Ganoderma lucidum extract, Group 8 received Acetaminophen+Standard Drug (silymarin) + 300 mg/kg body weight of Ganderma lucidum extract. Blood samples was collected via cardiac puncture within 24 hours of Sacrifice. The extent of the liver injury was determined by assessing the plasma levels of Tumor Necrosis Factor Alpha (TNF-α), Alpha Feto protein, Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP), Total bilirubin (TB), Conjugated bilirubin (CB), Unconjugated Bilirubin (UB), Albumin, Gamma Glutamyl Transaminase (GGT) and total protein (TP) using spectrophotometric method and ELISA as appropriate. Results: Oral administration of Acetaminophen significantly increased the plasma levels of the parameters accessed, suggesting severe liver damage in the rats. However, the treatment of Ganoderma lucidum decreased these hepatotoxic indices at a significant level of P <0.01 for TNF-α, AFP, ALT, AST, UB, TB, GGT and ALP, while Albumin and Conjugated Bilirubin were significantly decreased at a level of (P<0.05) in the Ganoderma lucidum + Acetaminophen-administered group compared to those of the control group. Conclusion: Thus, the results of the present investigation demonstrates that the Ganoderma lucidum provides significant hepatoprotective activity against acetaminophen-induced liver injury in wistar rats.
... It was recommended that RCTs should adopt standard reporting guidelines, for example, "Standard Protocol Items: Recommendations for Interventional Trials" (SPIRIT) or "Consolidated Standards of Reporting Trials" (CONSORT) for the planning, execution, and reporting of these trials [75,76]. Nearly three-quarters of cancer-related SRs (18/26, 69.2%) highlighted the need for studies to include specific populations; for example, to include homogenous study populations in terms of anticancer treatment and disease stage in studies assessing a variety of treatment interventions, including low bacterial diets, consumption of Reishi mushroom, supplementation of retinoic acid and parenteral nutrition [22,36,77,78], as well as assessing the risk of cancer in specific groups, for example, in studies addressing vitamin D and selenium (e.g., young people, men, individuals with low vitamin D or selenium status) [39,79]. Almost all SRs (25/26, 96.2%) highlighted the need for more studies assessing specific interventions; for example, those involving dietary patterns (e.g., intakes of dietary fiber of at least 30-40 mg/day [80]), the consumption of single foods (e.g., low to moderate doses of green tea [29]), the supplementation of macronutrients (e.g., the need for more palatable eicosapentaenoic acid formulations [81]), and the need to determine optimal dosages of micronutrients (e.g., selenium [82]), calcium [83], iron [84], or alternative supplements (e.g., ...
Background
Noncommunicable diseases (NCDs) are a global health problem and many risk factors associated with the development of NCDs are related to nutrition.
Aims
This study aimed to describe and summarize the research recommendations for primary research made in Cochrane nutrition systematic reviews (SRs) addressing NCDs, according to the evidence, population, intervention, comparison, outcome, time stamp (date of search), study design, time frame (length of follow‐up) and burden of disease (EPICOT+) framework.
Materials & Methods
We screened a database of Cochrane nutrition SRs ( n = 692) in March 2021 to identify those SRs addressing the four main NCDs (cardiovascular diseases, cancer, chronic respiratory diseases, and diabetes) and their nutrition‐related risk factors (obesity, unhealthy diets). The “implications for research” sections of included SRs (and the “search methods” sections for the time stamp item) were analyzed using EPICOT+.
Results
We included 150/692 SRs; most addressed cardiovascular diseases (38.6%), and cancer (17.3%). The EPICOT+ items with the most reported research recommendations were time stamp (98.7%), intervention (94.7%), study design (89.3%), and outcomes (86%), and the least reported were the time frame (52%), comparison (30%), and burden of disease (8%). Most SRs recommended more studies overall (98.7%), assessing specific interventions (93.3%) (e.g., specific foods/food groups and diets/dietary patterns, micronutrient/complementary supplements, nutrition education techniques, and policies/programs) and a range of clinical and patient‐related outcomes (84.7%). Recommendations related to study design and quality included the need for more randomized (72.7%), better quality (55.3%), larger (44.7%), and better reported (26%) studies with a long‐term duration of follow‐up (50.7%).
Discussion
Our findings show that research recommendations reported in Cochrane nutrition SRs addressing the four major NCDs and their nutrition‐related risk factors largely followed the EPICOT+ framework. For example, items that could be improved upon were the comparison and time frame items.
Conclusion
These recommendations could contribute more significantly to planning future primary studies addressing important evidence gaps and limitations in the current evidence base.
... Mushroom bioactive compounds have also been found to have anti-inflammatory and anti-oxidant properties, which may contribute to their anti-senescence effects [212]. For example, polysaccharides from Lentinus edodes (shiitake mushroom) have been shown to reduce oxidative stress and inflammation in aging mice, which may help delay the accumulation of senescent cells [78,213,214]. ...
Aging is a complex biological process that is influenced by both intrinsic and extrinsic factors. Recently, it has been discovered that reactive oxygen species can accelerate the aging process, leading to an increased incidence of age-related diseases that are characteristic of aging. This review aims to discuss the potential of mushrooms as a dietary intervention for anti-aging, focusing on their nutritional perspective. Mushrooms contain various bioactive compounds, including carbohydrates, bioactive proteins, fungal lipids, and phenolic compounds. These compounds have shown promising effectiveness in combating skin aging and age-related diseases. In vitro and in vivo studies have demonstrated that treatments with mushrooms or their extracts can significantly extend lifespan and improve health span. Furthermore, studies have aimed to elucidate the precise cellular and molecular mechanisms of action and the structure–activity relationship of mushroom bioactive compounds. These findings provide a strong basis for further research, including human clinical trials and nutritional investigations, to explore the potential benefits of mushrooms in real-life anti-aging practices. By exploring the anti-aging effects of mushrooms, this review aims to provide valuable insights that can contribute to the development of broader strategies for healthy aging.
... One of the most natural products widely studied in hematological malignancies like leukemia and lymphoma as a potential anticancer agent is G. lucidum [49]; in fact, recent in vitro and in vivo studies show promising results for its anticancer activity [27], since it is able to determine the activation of the host cell immune response [10], induction of cell differentiation, induction of phase II metabolizing enzymes, inhibition of urokinase-type plasminogen activator (uPA) and urokinase-type plasminogen activator receptor (uPAR) expression in tumor cells, direct cytotoxicity and inhibition of angiogenesis [30,[76][77][78][79]. G. lucidum has been found to have an antiproliferative effect in both laboratory and animal experiments [80], a cytotoxic effect by interrupting the tumor cell cycle and inducing apoptosis [81][82][83], and also NK cell cytotoxicity against various tumor cell lines [84]. ...
Triterpenoids, such as ganoderic acid, and polysaccharides, including β-D-glucans, α-D-glucans, and α-D-mannans, are the main secondary metabolites of the medicinal fungus Ganoderma lucidum. There is evidence of the effects of ganoderic acid in hematological malignancies, whose mechanisms involve the stimulation of immune response, the macrophage-like differentiation, the activation of MAP-K pathway, an IL3-dependent cytotoxic action, the induction of cytoprotective autophagy, and the induction of apoptosis. In fact, this compound has been tested in twenty-six different human cancer cell types and has shown an anti-proliferative activity, especially in leukemia, lymphoma, and myeloma lines. Moreover, research clarified the capability of molecules from Ganoderma lucidum to induce mitochondrial damage in acute promyelocytic leukemia cells, without cytotoxic effects in normal mononuclear cells. Active lipids extracted from the spores of this fungus have also been shown to induce apoptosis mediated by downregulation of P-Akt and upregulation of caspases-3, -8, and -9. Among in vivo studies, a study in BALB/c mice injected with WEHI-3 leukemic cells suggested that treatment with Ganoderma lucidum promotes differentiation of T- and B-cell precursors, phagocytosis by PBMCs, and NK cell activity. Our review presents data revealing the possibility of employing Ganoderma lucidum in hematological malignancies and incorporating it into clinical practice.
... These components exhibit antioxidant, anti-inflammatory, anti-tumor, anti-aging, and immunomodulatory effects [12]. Consequently, G. lucidum is extensively used in traditional Chinese medicine for the treatment of various diseases including cancer, cardiovascular diseases, nervous and immune system disorders [13][14][15]. ...
... They are also utilized to reduce the likelihood of cancer invasion (Jin et al. 2012.)and metastasis due to their antitumorous attributes. ...
The Indian Thar desert harbours a treasure trove of fungal diversity especially wild mushrooms. Ethanobotanical information reveals that mushroom flora of Rajasthan has great potential for medicinal value. In the present study,Phellorinia herculeana and Podaxis pistillaris growing amidst the sand dunes in Jaisalmer and Barmer districts of Rajasthan effectively inhibited the growth of various microbes paving their way for use as therapeutics.
... Case studies shows improvement [425][426][427][428][429] Mouse oral LD50: 170mg/kg [430] Diclofenac 75-100 mg daily 23 Nigella Sativa (thymoquinone) p53, NF-κB, PPARγ, STAT3, MAPK, and PI3K/AKT signaling pathways [431] improved treatment outcome in acute lymphoblastic leukemia in children [432] Oral mouse LD50: 29mL/kg [433] 400-500mg encapsulated oil twice daily, avoid during pregnancy Reishi Immunomodulation [434,435] 50% increased effectiveness of cancer chemotherapy [436] Oral mouse LD50: >10g/kg [437] 6-12g of Reishi extract per day ...
Cancer is amenable to low-cost treatments, given that it has a significant metabolic component, which can be effected through diet and lifestyle change at minimal cost. The Warburg hypothesis states that cancer cells have altered cell metabolism towards anaerobic glycolysis. Given this metabolic reprogramming in cancer cells, it is possible to target cancers metabolically by depriving them of glucose. In addition to dietary and lifestyle modifications which work on tumors metabolically, there are a panoply of nutritional supplements and repurposed drugs associated with cancer prevention, and better treatment outcomes. These interventions and their evidentiary basis are covered in the latter half of this review to guide future cancer treatment.
... Normalizes skin lesions when applied topically [424]. Case studies shows improvement [425][426][427][428][429] Mouse oral LD50: 170mg/kg [430] Diclofenac 75-100 mg daily Nigella Sativa (thymoquinone) p53, NF-κB, PPARγ, STAT3, MAPK, and PI3K/AKT signaling pathways [431] improved treatment outcome in acute lymphoblastic leukemia in children [432] Oral mouse LD50: 29mL/kg [433] 400-500mg encapsulated oil twice daily, avoid during pregnancy Reishi Immunomodulation [434,435] 50% increased effectiveness of cancer chemotherapy [436] Oral mouse LD50: >10g/kg [437] 6-12g of Reishi extract per day Ivermectin Regulates multiple signaling pathways [438,439] Case series showed improvement in patient symptoms when combined with dichloroacetate [440] Mouse oral LD50: >27mg/kg [441] 12-60mg 2x/week Dipyridamole Increases tumor chemosensitivity [442] Increases efficacy of other anti-cancer agents [443][444][445] Rat oral LD50: 8g/kg [446] 100 mg twice daily Intravenous Vitamin C Targeted killing (through intracellular generation of H2O2) of cancer cells [447] Improved life quality in cancer patients [448], lowered inflammation [449] Rat intravenous LD50 >4g/kg [450] 50-75 g IV as per protocol Dichloroacetate Inhibits dehydrogenase kinase to inhibit metabolic reprogramming by cancer cells [451] Greater treatment response, but no impact on survival [452] Rat oral LD50 5 g/kg [453] 500 mg two/three times daily Cannabinoids induction of cancer cell death by apoptosis and Useful in treating refractory chemotherapy THC Daily doses range from 10 to 800mg CBD and the inhibition of cancer cell proliferation [454] induced nausea and vomiting Case studies show possible benefit [455] Mouse oral LD50: 500mg/kg [456] CBD Mouse oral LD50: >100mg/kg [457] 5-8mg THC [458] Fenofibrate Stimulation of peroxisome proliferator activated receptor α (PPARα) [459] No clinical data Mouse oral LD50: 1.6g/kg [460] N/A Pao Pereira Inhibition of NF kappa B Signaling [461] Effectiveness in prostate cancer [462] Limited information N/A ...
Cancer is amenable to low-cost treatments, given that it has a significant metabolic component, which can be effected through diet and lifestyle change at minimal cost. The Warburg hypothesis states that cancer cells have altered cell metabolism towards anaerobic glycolysis. Given this metabolic reprogramming in cancer cells, it is possible to target cancers metabolically by depriving them of glucose. In addition to dietary and lifestyle modifications which work on tumors metabolically, there are a panoply of nutritional supplements and repurposed drugs associated with cancer prevention, and better treatment outcomes. These interventions and their evidentiary basis are covered in the latter half of this review to guide future cancer treatment.
... Today, the Ganoderma mushroom products are also widely available internationally as an alternative treatment in cancer diseases. The medicinal value of Ganoderma and other medicinal fungi has been critically evaluated in recent years (Jin et al. 2016;Money, 2016;Cör et al. 2022). ...
... lucidum) is a traditional Chinese medicine widely used in China (named Ling Zhi) for hundreds of years (Ahmad, 2018). As a medicinal and edible mushroom, G. lucidum has proved to possess diverse pharmacological activities, including antioxidant , antidiabetic (Ma et al., 2015), antimicrobial (Cor et al., 2018), anti-inflammatory (Cai et al., 2016), immunomodulatory (Li et al., 2020), and anticancer effects (Jin et al., 2016). Researchers have found that G. lucidum could exert its anticancer effects by directly killing cancer cells, inhibiting angiogenesis, inducing cell differentiation, and activating immune response of the host (Ahmad, 2018). ...
Cancer is a leading cause of death globally. Chemotherapy still plays an indispensable role in the clinical treatment of cancer. However, the emergence of multidrug resistance (MDR) has greatly obstructed the further application of chemotherapy agents. Ganoderma lucidum (G. lucidum) is a traditional Chinese medicine as well as an edible mushroom. In this study, we first explored the effect of six extract samples derived from G. lucidum on the cell viability of adriamycin-resistant human hepatocellular carcinoma multidrug-resistant cell subline (HepG-2/ADM). All these samples showed no obvious toxicity to cells; however, only G. lucidum ethanol extract could reverse resistance to doxorubicin and paclitaxel. Then the P-glycoprotein (P-gp) function in hepatocellular carcinoma G2 (HepG-2) and HepG-2/ADM cells was determined after incubated with these samples, and we found that G. lucidum ethanol extract could inhibit P-gp function in vitro. Furthermore, G. lucidum ethanol extract could reverse resistance to paclitaxel in HepG-2/ADM tumor-bearing mice in vivo, while the protein expression level of P-gp was unchanged. Taken together, these results indicated the potential role of G. lucidum ethanol extract in reversing MDR in the clinical treatment of hepatocellular carcinoma.
... In the food industry and medicine, natural polysaccharides have been used for a long time. Numerous studies have been carried out about bioactive polysaccharides especially, their structures and mechanisms in diseases [23][24][25] . Several years of research have proved that Ganoderma lucidum is an immunostimulant as well as a powerful antioxidant. ...
Ganoderma lucidum is a promising medicine with a high amount of antioxidants and calcium. The selection of appropriate drying process methods in food science has a chief role to reach the best final characteristics. This study aimed to investigate the effects of air velocity and temperature in the convective dryer, sample distance, and infrared power in infrared dryers on the drying kinetics and quality of Ganoderma lucidum slices. In addition, Response Surface Methodology based on central composition design was used to optimize and analyze drying conditions. The ranges of temperature and air velocity were 40–60 °C and 0.5–1.5 m/s, respectively in the convective drying process while the range of distance and infrared power was 4–16 cm and 500–1500 W, respectively in the infrared drying process. It is worth mentioning that antioxidant and calcium contents were greatly enhanced during the drying procedures. Moreover, the values of the total color difference ranged between 8.21 and 19.66 for the convective dryer and 8.14 and 28.85 for the infrared dryer. A kinetic study indicated that dried samples by the infrared dryer could rapidly reach equilibrium moisture content due to exposure to IR radiation. Consequently, the results indicated that the infrared dryer has better performance than the convective dryer regarding drying time, energy consumption, and amount of calcium and antioxidant.
... In vivo investigations revealed that the tumor growth of colorectal cancer cells xenograft nude mice fed with Ganoderma extracts was significantly suppressed [5]. Moreover, cancer patients who received combinational treatment of Ganoderma and chemo/radiotherapy responded positively than chemo/radiotherapy alone [6]. However, even it has been revealed that triterpenoids from Ganoderma could act as an emerging role in tumor suppression [7], the anti-cancer activity of Ganoderma RNAs remains unknown, though RNAs have been revealed to be abundant in Ganoderma [8], which is in accordance with our results (2.1 ± 0.4 mg/g). ...
Ganoderma lucidum (Ganoderma) is a famous Chinese herbal medicine which has been used clinically for thousands of years in China. Despite numerous studies on triterpenes and polysaccharides, the bioactivity of RNAs abundant in Ganoderma remains unknown. Here, based on LC-MS techniques, dihydrouracil, 5-methyluridine (m5U) and pseudouridine were identified at position 19, 52 and 53 of a new tRNAIle(GAU) which was isolated as the most abundant tRNA species in Ganoderma, and is the first purified tRNA from fungus. Cytotoxic screening of tRNA-half (t-half) and tRNA fragment (tRF) derived from this tRNA, as well as their mimics (t-half or tRF as antisense strand), demonstrated that the double-stranded form, i.e., tRF and t-halve mimics, exhibited stronger cytotoxicity than their single-stranded form, and the cytotoxicity of t-half mimic is significantly stronger than that of tRF mimic. Notably, the cytotoxicity of 3′-t-half mimic is not only much more potent than that of taxol, but also is much more potent than that of ganoderic acids, the major bioactive components in Ganoderma. Furthermore, 3′-t-half mimic_M2 (m5U modified) exhibited significantly stronger cytotoxicity than unmodified 3′-t-half mimic, which is consistent with the computational simulation showing that m5U modification enhances the stability of the tertiary structure of 3′-t-half mimic. Overall, the present study not only indicates t-halves are bioactive components in Ganoderma which should not be neglected, but also reveals an important role of post-transcriptional modification on tRNA in its fragments' cytotoxicity against cancer cells, which benefits the design and development of RNAi drugs from natural resource.
... A systematic review found that patients who had taken G. lucidum as an adjunct therapy with chemo/radiotherapy were more likely to respond positively compared to the orthodox treatment alone (RR 1.50; 95% CI 0.90-2.51, p = 0.02) [204]. Cao and colleagues [199] provide a comprehensive explanation of the research evidence for the anti-cancer actions of G. lucidum. ...
A significant proportion of cancer patients use forms of complementary medicine or therapies. An integrative approach to cancer management combines conventional medicine with evidence-based complementary medicines/therapies and lifestyle interventions, for the treatment and prevention of disease and the optimisation of health. Its basis is a holistic one; to treat the whole person, not just the disease. It makes use of adjunct technologies which may assist the clinician in diagnosis of early carcinogenesis and monitoring of treatment effectiveness. Many factors contribute to the development of cancer including some which are largely modifiable by the patient and which oncologists may be in a position to advise on, such as stress, poor nutrition, lack of physical activity, poor sleep, and Vitamin D deficiency. An integrative approach to addressing these factors may contribute to better overall health of the patient and better outcomes. Evidence-based complementary medicine approaches include the use of supplements, herbal medicine, various practices that reduce stress, and physical therapies. Individualised to the patient, these can also help address the symptoms and signs associated with cancer and its orthodox treatment.
... In the end, G. lucidum is widely used in various medicinal applications (Boa 2004;Wachtel-Galor et al. 2011). However, there are studies showing patients treated with G. lucidum experience adverse effects such as insomnia, digestive upsets, skin rashes, and hepatotoxicity (Jin et al. 2012). Long-term intake of G. lucidum was also reported to cause liver failure in humans. ...
Human consumption has outpaced meat production and manufacturing due to the rising human population and limited land for livestock agriculture. Meat consumption can have negative effects on human health, but meat production can negatively affect the environment by causing global warming and water pollution. Hence, this study produces the idea of using fungus as an alternative to replacing meat. Fungus is an ideal choice as a meat replacement because it has high nutritional content and a fast growth rate. The main objective of this review was to assess the nutritional potential of nine fungal species namely Fusarium venenatum, Neurospora intermedia, Tuber sp., Xerocomus badius, Ganoderma lucidum, Pleurotuseryngii, Agaricus bisporus, Pleurotus sajor-caju and Lentinula edodes and to determine which species is the best candidate for meat replacement. The nutritional values, toxicity, and growth rate of each fungus were assessed. Comparative data analysis suggests that F. venenatum, N. intermedia, P. eryngii, A. bisporus, P. sajor-caju, and L. edodes are found suitable for producing fungi-based meat.
... Several years of studies have confirmed that G. lucidum is an immunostimulant and a strong antioxidant. It can now be used as an adjunct to prevent the effects of chemotherapy and to tackle cancer (Jin et al., 2012). The different bioactive activities of triterpenoids and polysaccharides are shown in Figure 1. ...
Ganoderma lucidum is a very medicinal mushroom that has been utilized in Oriental medicine for many years. It has a wide range of pharmacological and therapeutic properties, and has been used for many years as a health promoter. It contains various biologically active compounds that improve the immune system and have antioxidant, antitumor, anti-inflammatory, antifungal, and antimicrobial properties. Active compounds include triterpenoids and polysaccharides, as well as proteins, lipids, phenolics, sterols, etc. In the following review, we summarize briefly their biological activities, such as antioxidant, anti-bacterial, anti-fungal, antitumor, anti-viral, and anti-inflammatory activity. Although Ganoderma has a number of medicinal effects that have been confirmed by the in vitro and in vivo studies summarised in this review, there are some limitations. Clinical trials face mainly a lack of pure constituents. Accurate identification of the compounds obtained is also problematic. In addition, most of the included studies were small, and there were concerns about the methodological quality of each study. Studies have shown that Ganoderma has valuable potential for the prevention and treatment of cancer. In any case, G. lucidum cannot be used as first-line therapy for cancer.
Background/Objectives: The combination of different fungal extracts could be beneficial to cancer patients due to their role in gut microbiota modulation and anti-inflammatory activity. The study aimed to evaluate whether fungal extract supplementation reduces postsurgical complications in patients with colorectal cancer undergoing curative surgery. Methods: Patients were randomized to receive the nutraceutical Micodigest 2.0 or a placebo until surgery. Surgical complications were evaluated using the Clavien-Dindo classification. We also assessed the effect of the nutraceutical on gut microbiota composition, inflammatory response, nutritional status, and quality of life. A subanalysis based on surgery type (robotic vs. non-robotic) was performed. Results: We included 46 patients who met the inclusion criteria, with 27 randomized to the intervention group and 19 to the placebo group, receiving treatment for three (2–4) weeks. Non-robotic surgery was performed in 35 (76.1%) patients. We found non-significant differences in postoperative complications (Micodigest 2.0: 25.9%, placebo: 26.3%; p = 0.9). In non-robotic surgery, we identified a non-significant reduction in postoperative complications (Micodigest 2.0: 25.0%, placebo: 36.4%; p = 0.7), as well as a significant increase in lymphocyte levels and a reduction in the neutrophil-to-lymphocyte ratio (p = 0.02). Micodigest 2.0 supplementation was also associated with significant changes in gut microbiota composition, as indicated by a decreased relative abundance of the phyla Firmicutes (p = 0.004) and Actinobacteria (p = 0.04). Conclusions: Micodigest 2.0 supplementation was associated with non-significant reductions in postoperative complications and significant modifications in gut microbiota composition. Limitations: The trial did not reach the calculated sample size.
More than fifty medicinal mushrooms exhibit diverse therapeutic properties, with Ganoderma species holding particular historical significance in human diets and traditional medicine, especially in Asia, where they are esteemed for their purported contributions to vitality and longevity. Extensive research involving both in vitro and in vivo investigations has been undertaken to elucidate the diverse metabolic activities associated with Ganoderma. Nonetheless, a contentious issue persists regarding the classification of Ganoderma as either a health-promoting food supplement or a therapeutic drug for medical purposes. Various Ganoderma based products, including coffee, powder, tea, beverages, syrups, and lotions, have been commercially promoted as efficacious food and drug supplements offering health benefits. The industry has grown substantially over the past three decades, resulting in many products saturating the market. Despite the substantial scale of the industry, it grapples with inherent challenges in establishing a robust market presence. This review provides a comprehensive overview of the current status of Ganoderma products and the industry while offering recommendations for fostering advanced research.
Background
Reishi, a medicinal mushroom, is increasingly used for symptom control by cancer patients worldwide. However, data around patients' experiences with Reishi in oncology are lacking, limiting safe, effective clinical applications. We thus sought to evaluate patient reported benefits and harms of using Reishi.
Methods
We conducted a cross-sectional survey among Chinese cancer patients using Reishi products, probing for symptom improvements and/or adverse events (AEs) after taking Reishi. Multivariable logistic regression models assessed whether socio-demographic or clinical factors, as well as duration of Reishi use or combination with other TCM herbs, were associated with being a “responder” – reporting “quite a bit” or “very much” symptom improvement.
Results
Among 1374 participants, more than half of participants reported that nausea (55 %), fatigue (52 %), poor appetite (51 %), and depression (50 %) improved quite a bit or very much after taking Reishi. In multivariate analyses, age <65 years (adjusted odds ratios [AOR] = 1.76, p = 0.001), diagnosis ≥ 10 years (AOR = 1.78, p = 0.018), and duration of Reishi use ≥ 1 year (1–3 years: AOR = 1.53, p = 0.045; 3–5 years: AOR = 2.04, p = 0.001; >5 years: AOR = 2.07, p < 0.001) were significantly associated with higher responder rates for symptom improvement. However, 125 (9.1 %) also reported a range of AEs, including dry mouth (5 %), constipation (4 %), insomnia (3 %), pruritus (3 %) and vertigo (3 %).
Conclusion
While majority of cancer patients using Reishi reported symptom improvements, some reported adverse effects. This information can assist clinicians in advising cancer patients on safe and effective use of Reishi and help identify specific outcomes for assessment in future prospective clinical trials.
Diabetes mellitus (DM) is a major metabolic disease endangering global health, with diabetic nephropathy (DN) as a primary complication lacking curative therapy. Sporoderm-broken spores of Ganoderma lucidum (GLP), an herbal medicine, has been used for the treatment of metabolic disorders. In this study, DN was induced in Sprague-Dawley rats using streptozotocin (STZ) and a high-fat diet (HFD), and the protective mechanisms of GLP were investigated through transcriptomic, metabolomic, and network pharmacology (NP) analyses. Our results demonstrated that GLP intervention ameliorated renal damage and inflammation levels in DN rats. Integrative metabolomic and transcriptomic analysis revealed that GLP treatment modulated glucose and cellular energy metabolisms by regulating relevant genes. GLP significantly suppressed the inflammations by impacting glucose and energy metabolism-related gene expression (Igfbp1 and Angptl4) and enhanced metabolic biomarkers of 4-Aminocatechol. In addition, NP analysis further indicated that GLP may efficiently alleviate DN via immune-related pathways. In conclusion, this study provides supportive evidence of the anti-inflammatory effects of GLP supplements, highlighting their potential for promising clinical applications in treating DN.
This study investigates the potential synergy effect of Ganoderma lucidum and Lentinus edodes mushroom extracts delivered through niosomes (composed of Span 40, Tween 40, and cholesterol) for anti‐cancer and antimicrobial applications. GC–MS analysis revealed bioactive compounds such as d‐limonene, ascorbic acid, and ergosterol in the extracts, known for their anti‐cancer and antimicrobial effects. The niosomal formulations exhibited improved physical properties, with sizes ranging from 96 to 160 nm and polydispersity index (PDI) values in the range of 0.29–0.54, suggesting that the niosomes had an acceptable size distribution and homogeneity. In cell culture studies, the niosomal formulations demonstrated significant cytotoxic effects on A549 lung cancer cells, with the combination of both extracts leading to a notable decrease in cell viability to 14.86%. Additionally, the combination of G. lucidum and L. edodes extracts in niosomal form showed varying and potent antimicrobial properties against pathogenic bacteria ( Pseudomonas aeruginosa and Staphylococcus aureus ) and fungi ( Candida albicans ) with lower minimum inhibitory concentration (MIC) values compared to their free form, indicating a potential synergistic effect. The findings highlight the potential synergistic anti‐cancer and antimicrobial effects of the combined mushroom extracts delivered through niosomes, offering valuable insights for developing novel drug delivery systems.
The patient was diagnosed with primary liver cancer featuring intrahepatic metastasis (Barcelona stage B; Stage IIB), hepatitis B infection, and post‐hepatitis B cirrhosis during the period of compensated liver function. Following a 7‐month regimen combining traditional Chinese herbal medicine (TCHM) with Renvatinib and Carrelizumab, the patient exhibited favorable tolerability, no bleeding risks, and stable tumor progression. The effectiveness of TCHM in this case was marked by significant symptom alleviation, reduced serum molecular markers, minimized adverse reactions, and obviated surgical intervention. Blood tests displayed alpha‐fetoprotein levels ranging from 8.85 to 20.65 IU/mL, with no increase in bleeding risks.
Ganoderma lucidum polysaccharide is the most widely used complementary therapy in cancer. The present study aims to investigate the possible interaction between Ganoderma lucidum polysaccharide and Docetaxel (a chemotherapy drug) and the first-line medication for prostate cancer treatment (Flutamide) and sensitizing the cells to these treatments. The cytotoxic effects of Ganoderma lucidum polysaccharide in combination with Docetaxel and Flutamide on prostate cancer cells were investigated by the MTT test, Hoechst staining, and flow cytometry. In addition, the expression of genes related to apoptosis, angiogenesis, Epithelial-Mesenchymal Transition pathway (EMT), and prostate cancer biomarkers by Real-Time PCR was investigated. The results demonstrated that IC50 values for Ganoderma lucidum polysaccharide (30 μM and 20 μM), Docetaxel (10 μM and 5 μM), and Flutamide (20 μM and 12 μM) with MTT were confirmed by flow cytometry in a dose and time-dependent manner. Regarding the high efficacy of Ganoderma lucidum polysaccharide in combination with Flutamide and Docetaxel, 10 μM and 5 μM Flutamide were used instead of 20 μM and 12 μM and 5 μM and 2 μM Docetaxel was used instead of 10 μM and 5 μM in PC3 and LNCap, respectively. Moreover, for the first time, it was shown that Ganoderma lucidum polysaccharide alone and in combination with Docetaxel and Flutamide significantly augmented apoptosis, reduced cell migration and colonization, and downregulated expression of KLK2 and EMT pathway genes in both PC3 and LNCap cell line (P < 0.01). Ganoderma lucidum polysaccharide synergistically increased the effect of Docetaxel and Flutamide and increased the sensitivity of the prostate cancer cell lines to these drugs. Therefore, it may provide a new therapeutic strategy against prostate cancer.
Cancer is amenable to low-cost treatments, given that it has a significant metabolic component, which can be affected through diet and lifestyle change at minimal cost. The Warburg hypothesis states that cancer cells have an altered cell metabolism towards anaerobic glycolysis. Given this metabolic reprogramming in cancer cells, it is possible to target cancers metabolically by depriving them of glucose. In addition to dietary and lifestyle modifications which work on tumors metabolically, there are a panoply of nutritional supplements and repurposed drugs associated with cancer prevention and better treatment outcomes. These interventions and their evidentiary basis are covered in the latter half of this review to guide future cancer treatment.
Edible/medicinal mushrooms have been traditionally used in Asian countries either in the cuisine or as dietary supplements and nutraceuticals. In recent decades, they have aroused increasing attention in Europe as well, due to their health and nutritional benefits. In particular, among the different pharmacological activities reported (antibacterial, anti-inflammatory, antioxidative, antiviral, immunomodulating, antidiabetic, etc.), edible/medicinal mushrooms have been shown to exert in vitro and in vivo anticancer effects on several kinds of tumors, including breast cancer. In this article, we reviewed mushrooms showing antineoplastic activity again breast cancer cells, especially focusing on the possible bioactive compounds involved and their mechanisms of action. In particular, the following mushrooms have been considered: Agaricus bisporus, Antrodia cinnamomea, Cordyceps sinensis, Cordyceps militaris, Coriolus versicolor, Ganoderma lucidum, Grifola frondosa, Lentinula edodes, and Pleurotus ostreatus. We also report insights into the relationship between dietary consumption of edible mushrooms and breast cancer risk, and the results of clinical studies and meta-analyses focusing on the effects of fungal extracts on breast cancer patients.
Presented research aimed to develop a spray drying process without the use of organic solvents for the preparation of novel Karaya gum polymer microparticles (MPs) of Ganoderma lucidum polysaccharide (GLP). The prepared microparticles were characterized and evaluated. Prepared novel karaya gum micro-particles loaded Ganoderma lucidum polysaccharide (GLP MPs) were observed an effect on cadmium (CAD) induced testicular toxicity. A total of 40 rats (male) was divided into 4 groups viz. 1. Control group, 2. GLP MPs (250 mg/kg, 60 days of b.w per day), 3. CAD (60 days of 30 mg/l/day), 4. GLP MPs + CAD. CAD was responsible for altering the sex hormones, oxidative stress and inflammatory cytokines. Furthermore, elevated levels of indicator of oxidative stress, malondialdehyde, and a reduced action of SOD, GSH, and CAT (antioxidant enzymes), were observed in the tissues of the testicles of CAD- treated group. Such harmful occurrences were followed by an up-regulation in proinflammatory cytokines (TNF-α, IL-1β) levels, protein expression of Nrf2, and HO-1 expression was decreased. GLP MPs pre-treatment significantly abrogated these toxic effects which were confirmed histologically. This study concluded that pre-treatment with GLP MPs exerts a protective effect against CAD-induced male reproductive testicular toxicity.
Background:
Low quality of life (QoL) in patients with non-small cell lung cancer (NSCLC) receiving adjuvant chemotherapy after radical resection is a major global health issue. High-quality evidence for the effectiveness of Shenlingcao oral liquid (SOL) as a complementary treatment in this patients is lacking at present.
Purpose:
To determine whether complementary SOL treatment in NSCLC patients receiving adjuvant chemotherapy would yield greater improvements in QoL than chemotherapy alone.
Study design:
We conducted a multicenter, randomized controlled trial of stages IIA-IIIA NSCLC patients undergoing adjuvant chemotherapy in seven hospitals.
Methods:
Using stratified blocks, participants were randomized in a 1:1 ratio to receive SOL combined with conventional chemotherapy or conventional chemotherapy alone. The primary outcome was the change in global QoL from baseline to the fourth chemotherapy cycle, and intention-to-treat analysis was applied with a mixed-effect model. Secondary outcomes were functional QoL, symptoms, and performance status scores at the 6-month follow-up. Missing data were handled with multiple imputation and a pattern-mixture model.
Results:
Among 516 randomized patients, 446 (86.43%) completed the study. After the fourth chemotherapy cycle, in comparison with the control group, patients receiving SOL showed a lower reduction in mean global QoL (-2.76 vs. -14.11; mean difference [MD], 11.34; 95% confidence interval [CI], 8.28 to 14.41), greater improvement in physical function (MD, 11.61; 95% CI, 8.57 to 14.65), role function (MD, 10.15; 95% CI, 5.75 to 14.54), and emotional function (MD, 4.71; 95% CI, 1.85 to 7.57), and greater improvements in lung cancer-related symptoms (e.g., fatigue, nausea/vomiting, and appetite loss) and performance status during the 6-month follow-up period (treatment main effect, p < 0.05).
Conclusion:
SOL treatment for NSCLC patients receiving adjuvant chemotherapy can significantly improve QoL and performance status within 6 months after radical resection.
Trial registration:
ClinicalTrials.gov identifier: NCT03712969.
For centuries, Ganoderma has been used as a traditional medicine in Asian countries to prevent and treat various diseases. Numerous publications are stating that Ganoderma species have a variety of beneficial medicinal properties, and investigations on different metabolic regulations of Ganoderma species, extracts or isolated compounds have been performed both in vitro and in vivo. However, it has frequently been questioned whether Ganoderma is simply a dietary supplement for health or just a useful “medication” for restorative purposes. More than 600 chemical compounds including alkaloids, meroterpenoids, nucleobases, nucleosides, polysaccharides, proteins, steroids and triterpenes were extracted and identified from Ganoderma, with triterpenes serving as the primary components. In recent years, Ganoderma triterpenes and other small molecular constituents have aroused the interest of chemists and pharmacologists. Meanwhile, considering the significance of the triterpene constituents in the development of new drugs, this review describes 495 compounds from 25 Ganoderma species published between 1984 and 2022, commenting on their source, biosynthetic pathway, identification, biological activities and biosynthesis, together with applications of advanced analytical techniques to the characterization of Ganoderma triterpenoids.
CAM is used by about 40% of cancer patients in Western Countries, with peaks of 80% for breast cancer patients. Cancer patients use CAM to boost immune function, to control cancer symptoms and treatment-related side effects, and to improve health-related quality of life (HR-QoL) and survival. Unfortunately, self-prescription of natural remedies in cancer patients can lead to unexpected toxicities and can reduce the effectiveness of cancer therapy. Although CAM usually refers to all the “natural or organic” products/methods that are generally considered less toxic, there are concerns about drug interactions, especially in patients participating in clinical trials with experimental agents. Despite the claims of the promising and potential benefits made by prescribers, many CAMs lack clear scientific evidence of their safety and efficacy. Given the widespread use of CAM—both clearly declared and overt—in this review, we focused on the most important known data on the risk of interactions between biologics and oncology drugs with the goal of opening up CAM in accordance with the meaning of integrative medicine.
Abstract The CONSORT statement is used worldwide to improve the reporting of randomised controlled trials. Kenneth Schulz and colleagues describe the latest version, CONSORT 2010, which updates the reporting guideline based on new methodological evidence and accumulating experience. To encourage dissemination of the CONSORT 2010 Statement, this article is freely accessible on bmj.com and will also be published in the Lancet, Obstetrics and Gynecology, PLoS Medicine, Annals of Internal Medicine, Open Medicine, Journal of Clinical Epidemiology, BMC Medicine, and Trials.
Anticancer cytotoxic agents go through a process by which their antitumor activity—on the basis of the amount of tumor shrinkage they could generate—has been investigated. In the late 1970s, the International Union Against Cancer and the World Health Organization introduced specific criteria for the codification of tumor response evaluation. In 1994, several organizations involved in clinical research combined forces to tackle the review of these criteria on the basis of the experience and knowledge acquired since then. After several years of intensive discussions, a new set of guidelines is ready that will supersede the former criteria. In parallel to this initiative, one of the participating groups developed a model by which response rates could be derived from unidimensional measurement of tumor lesions instead of the usual bidimensional approach. This new concept has been largely validated by the Response Evaluation Criteria in Solid Tumors Group and integrated into the present guidelines. This special article also provides some philosophic background to clarify the various purposes of response evaluation. It proposes a model by which a combined assessment of all existing lesions, characterized by target lesions (to be measured) and nontarget lesions, is used to extrapolate an overall response to treatment. Methods of assessing tumor lesions are better codified, briefly within the guidelines and in more detail in Appendix I. All other aspects of response evaluation have been discussed, reviewed, and amended whenever appropriate.
Prostate cancer (PCa) is the most common male malignancy in many Western countries. Primary PCa is hormone dependent and is manageable by hormonal therapy. However, it rapidly develops to hormone-refractory tumors due to the accumulation of mutations in the androgen receptor and/or the acquisition of alternative cellular pathways that support proliferation and inhibit apoptosis of prostate cancer. To date, no effective therapy is available for clinically hormone-insensitive or hormone-refractory stages of prostate cancer.
Toll-like receptors (TLRs) mediate recognition of a wide range of microbial products including lipopolysaccharides, lipoproteins, flagellin, and bacterial DNA, and signaling through TLRs leads to the production of inflammatory mediators. In addition to TLRs, many other surface receptors have been proposed to participate in innate immunity and microbial recognition, and signaling through some of these receptors is likely to cooperate with TLR signaling in defining inflammatory responses. In this report we have examined how dectin-1, a lectin family receptor for beta-glucans, collaborates with TLRs in recognizing microbes. Dectin-1, which is expressed at low levels on macrophages and high levels on dendritic cells, contains an immunoreceptor tyrosine-based activation motif-like signaling motif that is tyrosine phosphorylated upon activation. The receptor is recruited to phagosomes containing zymosan particles but not to phagosomes containing immunoglobulin G-opsonized particles. Dectin-1 expression enhances TLR-mediated activation of nuclear factor kappa B by beta-glucan-containing particles, and in macrophages and dendritic cells dectin-1 and TLRs are synergistic in mediating production of cytokines such as interleukin 12 and tumor necrosis factor alpha. Additionally, dectin-1 triggers production of reactive oxygen species, an inflammatory response that is primed by TLR activation. The data demonstrate that collaborative recognition of distinct microbial components by different classes of innate immune receptors is crucial in orchestrating inflammatory responses.
Preclinical studies have established that the Ganoderma lucidum polysaccharide (GLPS) fractions have potent anti-tumor activity, which has been associated with the immuno-stimulating effects of GLPS. However, it is unclear whether GLPS has immuno-modulating effects in humans in vivo. This study aimed to investigate the effects of Ganopoly, the polysaccharides fractions extracted from G. lucidum, on the immune function of advanced-stage cancer patients. Thirty-four advance-stage cancer patients were entered onto this study, and treated with 1800 mg Ganopoly, three times daily orally before meals for 12 weeks. Immune parameters (cytokines, T cell subsets, mitotic response to phytohemagglutinin (PHA) and natural killer activity) were compared between baseline and after 12-week treatment. Thirty patients are assessable for their immune functions. Treatment of Ganopoly for 12 weeks resulted in a significant (P < 0.05) increase in the mean plasma concentrations of interleukin (IL-2), IL-6, and interferon (IFN)-gamma, whereas the levels of IL-1 and tumor necrosis factor (TNF-alpha) were significantly (P < 0.05) decreased. A marked variability among patients with advanced-stage cancer was observed in the numbers of each lymphocyte subset at baseline. The mean absolute number of CD56+ cells was significantly (P < 0.05) increased after 12-week treatment of Ganopoly, whereas the numbers of CD3+, CD4+, and CD8+ were just marginally increased compared to baseline levels, with the CD4:CD8 T cell ratios unchanged. PHA responses after 12-week treatment with Ganopoly were enhanced in most patients, when compared to pretreatment baselines (P < 0.05). In addition, Ganopoly treatment resulted in a significant increase (P < 0.05) in the mean NK activity compared to baselines (34.5 +/- 11.8% vs 26.6 +/- 8.3%). The present study indicates that Ganopoly enhanced the immune responses in patients with advanced-stage cancer. Clinical evaluations of response and toxicity are ongoing.
Cochrane Reviews have recently started including the quantity I 2 to help readers assess the consistency of the results of studies in meta-analyses. What does this new quantity mean, and why is assessment of heterogeneity so important to clinical practice?
Systematic reviews and meta-analyses can provide convincing and reliable evidence relevant to many aspects of medicine and health care.1 Their value is especially clear when the results of the studies they include show clinically important effects of similar magnitude. However, the conclusions are less clear when the included studies have differing results. In an attempt to establish whether studies are consistent, reports of meta-analyses commonly present a statistical test of heterogeneity. The test seeks to determine whether there are genuine differences underlying the results of the studies (heterogeneity), or whether the variation in findings is compatible with chance alone (homogeneity). However, the test is susceptible to the number of trials included in the meta-analysis. We have developed a new quantity, I 2, which we believe gives a better measure of the consistency between trials in a meta-analysis.
Assessment of the consistency of effects across studies is an essential part of meta-analysis. Unless we know how consistent the results of studies are, we cannot determine the generalisability of the findings of the meta-analysis. Indeed, several hierarchical systems for grading evidence state that the results of studies must be consistent or homogeneous to obtain the highest grading.2–4
Tests for heterogeneity are commonly used to decide on methods for combining studies and for concluding consistency or inconsistency of findings.5 6 But what does the test achieve in practice, and how should the resulting P values be interpreted?
A test for heterogeneity examines the null hypothesis that all studies are evaluating the same effect. The usual test statistic …
The popular edible mushroom Ganoderma lucidum (Reishi) has been widely used for the general promotion of health and longevity in Asian countries. The dried powder of Ganoderma lucidum was popular as a cancer chemotherapy agent in ancient China. The authors recently demonstrated that Ganoderma lucidum inhibits constitutively active transcription factors nuclear factor kappa B (NF-kappaB) and AP-1, which resulted in the inhibition of expression of urokinase-type plasminogen activator (uPA) and its receptor uPAR. Ganoderma lucidum also suppressed cell adhesion and cell migration of highly invasive breast and prostate cancer cells, suggesting its potency to reduce tumor invasiveness. Thus, Ganoderma lucidum clearly demonstrates anticancer activity in experiments with cancer cells and has possible therapeutic potential as a dietary supplement for an alternative therapy for breast and prostate cancer. However, because of the availability of Ganoderma lucidum from different sources, it is advisable to test its biologic activity.
Antitumor mAb bind to tumors and activate complement, coating tumors with iC3b. Intravenously administered yeast beta-1,3;1,6-glucan functions as an adjuvant for antitumor mAb by priming the inactivated C3b (iC3b) receptors (CR3; CD11b/CD18) of circulating granulocytes, enabling CR3 to trigger cytotoxicity of iC3b-coated tumors. Recent data indicated that barley beta-1,3;1,4-glucan given orally similarly potentiated the activity of antitumor mAb, leading to enhanced tumor regression and survival. This investigation showed that orally administered yeast beta-1,3;1,6-glucan functioned similarly to barley beta-1,3;1,4-glucan with antitumor mAb. With both oral beta-1,3-glucans, a requirement for iC3b on tumors and CR3 on granulocytes was confirmed by demonstrating therapeutic failures in mice deficient in C3 or CR3. Barley and yeast beta-1,3-glucan were labeled with fluorescein to track their oral uptake and processing in vivo. Orally administered beta-1,3-glucans were taken up by macrophages that transported them to spleen, lymph nodes, and bone marrow. Within the bone marrow, the macrophages degraded the large beta-1,3-glucans into smaller soluble beta-1,3-glucan fragments that were taken up by the CR3 of marginated granulocytes. These granulocytes with CR3-bound beta-1,3-glucan-fluorescein were shown to kill iC3b-opsonized tumor cells following their recruitment to a site of complement activation resembling a tumor coated with mAb.
Polysaccharides derived from fungi and plants have been increasingly used as dietary supplement with therapeutic intention for cancer. However, whether these polysaccharides from different sources and structures can elicit similar immunological effects remain unknown. This study aims to investigate and compare the effects of selected groups of purified and crude polysaccharides on human dendritic cells (DCs), the most potent antigen-presenting cells. The selected polysaccharides were from Ganoderma lucidum [(GL) Lingzhi, Reishi], a medicinal mushroom commonly used by oriental; and barley glucan, a purified polysaccharide with known in vivo immunomodulating effect. We found that purified polysaccharides from GL mycelium could induce human PBMC proliferation and phenotypic and functional maturation of DCs with significant IL-12 and IL-10 production. Polysaccharides of GL spore and barley were both rather weak immunostimulator in vitro. In general, all these polysaccharides did not polarize T cells into either T(h)1 or T(h)2 or regulatory T cells, except for crude spore polysaccharides-treated DCs which could suppress T cell proliferation with IL-10 production. This study revealed the polysaccharides of different sources have different immune potency and effect on human immune cells including DCs. Our study also provides a reproducible biological platform for comparing the potential therapeutic effects of different herbal-derived polysaccharides in the future.
Cancer is one of the most common severe diseases in Canadian children, and chemotherapy treatment leads to numerous, potentially fatal, adverse side effects including febrile neutropenia and leukopenia. In an attempt to prevent opportunistic infections, Ganoderma lucidum, a mushroom that has been used in Traditional Chinese Medicine for thousands of years, is being used by some people as an adjunctive to chemotherapy to help boost the immune system. Although extensive research is being conducted to determine its immunostimulatory properties, there is essentially no data on toxicity.
The purpose of this study was to determine toxicity of low and high concentrations of 3 different extracts of G. lucidum (GL, Reishi and PSGL) on the viability of 1) Jurkat E6.1 cells, 2) LG2 cells, and 3) PBMCs isolated from a) healthy adults, b) healthy children, and c) paediatric patients undergoing chemotherapy.
When Jurkat E6.1 and LG2 cells were treated with increasing concentrations of the 3 extracts, both time- and concentration- dependent decreases in cell viability were observed. However, when human PBMCs were treated with the same extracts, variable results were obtained. Although there was no consistent pattern, toxicity was observed in PBMCs.
This is the first study that examines the toxicity of 3 different extracts of G. lucidum in both adultsâ and children's PBMCs. Contrary to previous belief, our results suggest that extracts of G. lucidum should be used with caution as there appears to be potential for toxicity.
A systematic review may encompass both odds ratios and mean differences in continuous outcomes. A separate meta-analysis of each type of outcome results in loss of information and may be misleading. It is shown that a ln(odds ratio) can be converted to effect size by dividing by 1.81. The validity of effect size, the estimate of interest divided by the residual standard deviation, depends on comparable variation across studies. If researchers routinely report residual standard deviation, any subsequent review can combine both odds ratios and effect sizes in a single meta-analysis when this is justified. Copyright © 2000 John Wiley & Sons, Ltd.
Objective: To evaluate the effectiveness of Wuse - Lingzhi - Jiaonang on reducing adverse effects of radiotherapy and promoting the function of immune system in patients with nasopharyngeal cancer (NPC). Methods: A total of 72 patients with NPC who received radiotherapy were randomized into two arms treated (n = 36) and control (n = 36). In the treated group Wuse - Lingzhi - Jiaonang was administered orally during radiotherapy while patients in the control group received vitamin C 600mg/day. The patients' feeling of thirsty, appetite, buccal mucosa reaction, peripheral hemoglobin, RBC, WBC and conversion rate of lymphocytes, serous index of EB virus, NK cell levels before, during and after medication were examined in both groups. Results: The conversion rate of WBC and lymphocyte were significantly higher in the treated group as compared with the control group, but the other parameters showed no significant differences between these two groups. Conclusion: Wuse - Lingzhi - Jiaonang may be helpful, in improving the function of immune system in NPC patients receiving radiotherapy but it does not reduce the side effects of radiotherapy.
Background: Objective tumor response is a common endpoint in daily practice as well as in clinical trials to evaluate the efficacy of anti-cancer agents. Traditionally, the standard World Health Organization (WHO) criteria has been adopted in these contexts. However, the recent development of new classes of anti-cancer agents and progress in imaging technology have required new methodology to evaluate response to treatment. Recently, the Response Evaluation Criteria in Solid Tumors Group (RECIST) proposed new guidelines using unidimensional measurement. Theoretically, the simple sum of the maximum diameters of individual tumors is more linearly related to cell kill than is the sum of the bidimensional products. To validate these new guidelines, we have compared the standard WHO response criteria with the new RECIST guidelines in the same patient population. Methods: Data from 79 patients enrolled in eight prospective phase II studies at Samsung Medical Center were retrospectively re-analyzed to determine the concordance between the two response criteria. The two response criteria were applied separately, and the results were compared using the K statistic to test concordance for overall response rate. Results: The overall response rate according to the WHO criteria was 31.6%. Using the RECIST criteria, nine patients were reclassified and the overall response rate was 30.4%. There was excellent agreement between the unidimensional and bidimensional criteria in 23 of 25 responses (92%). The K statistic for concordance for overall response was 0.91. Conclusions: We conclude that the new RECIST guidelines are comparable to the old response criteria in evaluating response in solid tumors. Moreover, the new guidelines are just as simple and reproducible in the measurement of response in daily practice as they are in clinical trials.
Preclinical studies have established that the polysaccharide fractions of Ganoderma lucidum have potent immunomodulating effects. A recent clinical study of healthy volunteers demonstrated that G. lucidum did not affect their immune functions. The present open-labeled study aimed to evaluate the effects of water-soluble G. lucidum polysaccharides (Ganopoly) in patients with advanced colorectal cancer. Forty-seven patients were enrolled and treated with Ganopoly at 5.4 g/day for 12 weeks. In 41 assessable cancer patients, treatment with Ganopoly tended to increase mitogenic reactivity to phytohemagglutinin; counts of CD3, CD4, CD8, and CD56; plasma concentrations of interleukin (IL)-2, IL-6, and interferon (IFN)-γ; and NK activity, but to decrease the plasma concentrations of IL-1 and tumor necrosis factor (TNF)-α. No statistical significance was observed when a comparison was conducted between baseline values and those after 12-week treatment with Ganopoly. The changes of IL-1 were correlated with those of IL-6, IFN-γ, CD3, CD4, CD8, and NK activity (p < 0.05), and IL-2 changes were correlated with those for IL-6, CD8, and NK activity. The results indicate that Ganopoly may have beneficial immunomodulating effects in patients with advanced colorectal cancer. Further studies are needed to explore the mode of action, efficacy, and safety of Ganopoly in cancer patients.
There is an increasing interest in identifying effective and safe constituents from medicinal mushrooms for cancer prevention and treatment. Ganoderma lucidum has been used for this purpose, which is given as a single agent, or in combination with herbs or synthetic chemotherapeutic agents. Various polysaccharides (in particular β-D-glucans and glycoproteins) and triterpenoids have been found to be the major active constituents responsible for the chemopreventive and tumoricidal activity of G. lucidum. These compounds exerted promising cancer preventive and anticancer activity in animal (mouse and rat) studies. However, randomized, placebo-controlled, and multicenter clinical studies using G. lucidum have rarely been reported. In a randomized, placebo-controlled clinical study, 38 (26.6%) of 143 cancer patients had stable disease for 12 weeks or more (range, 12−50 weeks) when treated with Ganoply (a G. lucidum polysaccharide extract) orally at 1800 mg three times daily for 12 weeks. Palliative effects on cancer-related symptoms, such as sweating and insomnia, have been observed in many patients. Ganopoly was well tolerated, with five moderate adverse events recorded. These initial findings indicate that G. lucidum may represent a practical and promising approach for cancer prevention and cancer treatment. Further studies are required to establish the relationship between G. lucidum intake dose and cancer risks and to investigate the efficacy and safety when used alone or in combination with chemotherapy.
Preclinical studies have established that the polysaccharide fractions of Ganoderma lucidum (Ling Zhi, reishi mashroom) have potential antitumor activity. Recent clinical studies have demonstrated that G. lucidum polysaccharides enhanced host immune functions (e.g., enhanced natural killer cell activity) in patients with advanced solid tumor, although objective response was not observed. A randomized double-blind, placebo-controlled, multicenter clinical trial was conducted to evaluate the efficacy and safety of the G. lucidum polysaccharides, Ganopoly®, in patients with advanced lung cancer. Sixty-eight patients with histologically confirmed advanced lung cancer were enrolled. Eligibility criteria included con. rmation of diagnosis, objective measurable disease, a Karnofsky performance score і60, life expectancy of 12 weeks or greater, no recent or concomitant anticancer therapy, and informed consent. Patients were evaluated with respect to their extent of disease and quality of life (Karnofsky score), and hematologic and selected immunological and biochemical studies at baseline and after 12 weeks of treatment with oral Ganopoly or placebo at 600 mg three times daily. Patients in both groups were similar with respect to age, sex, treatment history, and lung tumor histology.
Despite the popularity of medicinal mushrooms, most are not well researched in terms of clinical efficacy and toxicity. We have completed seven clinical trials of Ganoderma lucidum in several diseases including cancer, Type II diabetes, coronary heart disease, chronic hepatitis B, and neurasthenia. Most of these studies were randomized, double-blind, multi-centered and placebo controlled. The results arising from these studies are promising. For example, treatment with Ganopoly for 12 weeks showed hypoglycemic activity in Type II diabetes, improved the symptoms/signs of patients with coronary heart disease or neurasthenia, and produced some antiviral and liver protective effects in patients with chronic hepatitis B infection. However, the same treatment regimen did not result in any objective response in late-stage cancer patients, although some stable disease status was observed. Ganopoly appeared to enhance immune functions in some cancer patients, but the results have yet to be confirmed. Ganopoly was generally well tolerated. Overall, the findings from all these clinical studies suggest that Ganopoly may have multiple pharmacological activities, although the activities are minor, moderate, or lacking as a result of many factors, such as inappropriate dosage regimen, difficulties in finding suitable biomarkers and end points, large interpatient variability in responses to the treatment, and unknown mode of action. Well designed clinical studies are needed to explore the mode of action, efficacy and safety of G. lucidum in patients.
BACKGROUND
Natural cytotoxicity, mediated by natural killer (NK) cells and cells with lymphokine-activated killer (LAK) activity, is believed to play an important role in host anti-cancer defense mechanisms.METHODS
The authors critically review recent publications on the role of natural cytotoxicity in patients with cancer.RESULTSIn patients with cancer, several studies have noted variations in the numbers and activity of NK and cells with LAK activity in different body compartments. NK cell activity in the peripheral blood lymphocytes (PBLs) is higher than that found in lymph nodes and within tumors, and this appears to be due to the presence of suppressor factors. The natural cytotoxicity of PBLs in patients with different types of cancers varies. However, there appears to be a trend for natural cytotoxicity to be reduced in certain cancer patients, possibly related to tumor volume or dissemination. Anti-cancer treatments (e.g., surgery, hormonal modulation, radiotherapy and chemotherapy) can also result in suppression of natural cytotoxicity, although the long-term effect on response to treatment and development of metastases is at present unknown.CONCLUSIONSNK and LAK cells, through the use of immune biologic modifiers, have been demonstrated to have a therapeutic role in the treatment of human cancers. Further studies are required to determine the optimal dosages and combinations of chemotherapeutic agents, the timing of surgery, and the adjuvant use of immune biologic response modifiers. An increasing awareness and understanding of this field, may allow for the future development of anti-cancer therapies. Cancer 1996;77:1226-43.
Natural killer (NK) cell cytotoxicity is an effective defense against metastatic tumor cells or viruses in the blood. However, NK cytotoxicity against tumor cells may be inhibited by a fibrinogen coat adhered to the surface of tumor cells. Ganoderma lucidum (G. lucidum) polysaccharides have been reported for their inhibitory ability on the adhesion of type I collagen, hyaluronan, fibronectin and laminin to integrins that were highly expressed on melanoma cells, and were therefore capable of enhancing NK cytotoxicity to tumor cells. In this study, we investigated the effect of G. lucidum polysaccharides on fibrinogen's adhesion to melanoma cells and NK cytotoxicity to tumor cells. Melanoma cells B16 and A375 were cultured and analyzed using flow cytometry. Human NK cells were isolated and analyzed using an NK cytotoxic assay. The results showed that polysaccharides extracted from G. lucidum inhibit the adhesion of fibrinogen to melanoma cells, and reverse the blocking effect of the fibrin coat on NK cytotoxicity against melanoma cells.
Leukopenia and immunity impairment usually occur during cancer therapy. Citronellol, an oil soluble compound derived from the geranium, has anticancer and antiinflammatory properties, as well as promoting wound healing. Ganoderma lucidum, Codonopsis pilosula and Angelicae sinensis are traditional Chinese herbs, all of which have proven immunomodulatory functions in laboratory-based research. This randomized, double-blind, placebo-controlled study examined whether the Chinese medicinal herb complex (CCMH; a mixture of citronellol and extracts of G. lucidum, C. pilosula and A. sinensis) improves the immune cell counts of cancer patients receiving chemotherapy and/or radiotherapy. A total of 105 cancer patients receiving chemotherapy or radiotherapy were enrolled. The quantities of immune cells in the blood of the subjects were determined before and after 6 weeks of cancer treatment, with either CCMH or a placebo. CCMH significantly reduced the depletion of leukocytes (14.2% compared with 28.2%) and neutrophils (11.0% compared with 29.1%). Analysis of the lymphocyte phenotype revealed that the patients receiving the placebo had reduced CD4 lymphocytes and natural killer (NK) cells than the CCMH-treated patients. Treatment with CCMH for patients receiving chemotherapy and/or radiotherapy may improve their immune function, improving their ability to fight off the cancer, as well as any secondary infections that could compromise their treatment and their health.
This chapter discusses medicinal benefits of the Mushroom Ganoderma. Recently, the fruit body and liquid-cultured mycelium of Ganoderma have been reported to contain polysaccharides which inhibit the growth of tumors. Identified as glucans, one of the major constituents in the cell wall of fungi, they appear to increase bodily resistance against the growth of tumors, induce the production of interferon, enhance the immunity function, and kill tumor cells within the body. The role of medicinal mushrooms in metabolic regulation is gaining greater attention. Their use in the development and application of beneficial biological activities offers an advantage in that the active principle is safe and can be tolerated by humans. Cultivation of such mushrooms provides an adequate supply but is unnecessary if mycelial cultures grown in large-scale fermentations can produce the same active principle. Finally, the search for new uses for the traditional medicinal fungi continues and the public should be educated about their potential value.
In recent years several investigators have developed procedures for measuring the quality of life of individuals. This paper focuses on an empirical approach to defining the main determinants of quality of life and the development and application of procedures for surveying the importance of each component in representative samples of 3 age groups of Americans. These age groups included those persons 30, 50, and 70 years of age. The survey also included reports by these persons concerning the extent to which their needs and wants were met with respect to each of these components. By using the critical incident technique it was found that there were 15 components that included all of the 6,500 activities and experiences reported by a wide variety of Americans from various geographic areas as contributing either positively or negatively to their quality of life. In the survey of 500 men and 500 women at each of the 3 age levels it was found that the 5 dimensions they most frequently described as important included: health, children, understanding yourself, work, and spouse. The 5 dimensions for which they reported their needs and wants were least well met were: participating in government, active recreation, learning and education, creative expression, and helping others. The 5 dimensions that correlated most highly with their reports of overall quality of life at present were: material comforts, work, health, active recreation, and learning and education. Suggestions are made for revising these procedures for use with persons with a disability to improve their quality of life.
On the initiative of the World Health Organization, two meetings on the Standardization of Reporting Results of Cancer Treatment have been held with representatives and members of several organizations. Recommendations have been developed for standardized approaches to the recording of baseline data relating to the patient, the tumor, laboratory and radiologic data, the reporting of treatment, grading of acute and subacute toxicity, reporting of response, recurrence and disease-free interval, and reporting results of therapy. These recommendations, already endorsed by a number of organizations, are proposed for international acceptance and use to make it possible for investigators to compare validly their results with those of others.
Natural cytotoxicity, mediated by natural killer (NK) cells and cell with lymphokine-activated killer (LAK) activity, is believed to play an important role in host anti-cancer mechanisms.
The authors critically review recent publications on the role of natural cytotoxicity in patients with cancer.
In patients with cancer, several studies have noted variations in the numbers and activity of NK and cells with LAK activity in different body compartments. NK cell activity in the peripheral blood lymphocytes (PBLs) is higher than that found in lymph nodes and within tumors, and this appears to be due to the presence of suppressor factors. The natural cytotoxicity of PBLs in patients with different types of cancers varies. However, there appears to be a trend for natural cytotoxicity to be reduced in certain cancer patients, possibly related to tumor volume or dissemination. Anti-cancer treatments (e.g., surgery, hormonal modulation, radiotherapy and chemotherapy) can also result in suppression of natural cytotoxicity, although the long-term effect on response to treatment and development of metastases is at present unknown.
NK and LAK cells, through the use of immune biologic modifiers, have been demonstrated to have a therapeutic role in the treatment of human cancers. Further studies are required to determine the optimal dosages and combinations of chemotherapeutic agents, the timing of surgery, and the adjuvant use of immune biologic response modifiers. An increasing awareness and understanding of this field, may allow for the future development of anti-cancer therapies.
Farnesyl protein transferase (FPT) catalyzes the posttranslational farnesylation of the cysteine residue located in the carboxyl-terminal tetrapeptide of the Ras oncoprotein. Prenylation of this residue is essential for membrane association and cell transforming activities of Ras. Inhibitors of FPT have been demonstrated to inhibit Ras-dependent cell transformation and thus represent a potential therapeutic strategy for the treatment of human cancers (1). In the present study, the inhibitory principles for protein prenyltransferases were isolated and identified from Ganoderma lucidum and garlic. The inhibitors from Ganoderma lucidum were identified as ganoderic acid A and ganoderic acid C by comparison with the reported spectral data. Ganoderic acid A has an IC50 value of 100 microM against FPT and its methyl ester (methyl ganoderate A) has an IC50 value of 38 microM for the same enzyme. These inhibitors appear to be competitive with farnesyl pyrophosphate (FPP), and Ki values of ganoderic acid A and methyl ganoderate A are 54 microM and 20 microM, respectively. The inhibitors from garlic were identified as diallyl thiosulfinate (allicin), methyl allyl thiosulfinate, and allyl methyl thiosulfinate. These inhibitors are more effective against geranylgeranyl protein transferase (GGPT) than FPT and IC50 values of allicin, methyl allyl thiosulfinate, and allyl methyl thiosulfinate for GGPT were 43 microM, 57 microM, and 53 microM, respectively. Methyl allyl thiosulfinate appears to be competitive with geranylgeranyl pyrophosphate (GGPP) and its Ki was determined to be 15 microM. The molecular structures of triterpenes and thiosulfinates are expected to be useful in designing lead compounds for new potent antitumour agents.
Six new highly oxygenated lanostane-type triterpenes, called ganoderic acid gamma (1), ganoderic acid delta (2), ganoderic acid epsilon (3), ganoderic acid zeta (4), ganoderic acid eta (5) and ganoderic acid theta (6), were isolated from the spores of Ganoderma lucidum, together with known ganolucidic acid D (7) and ganoderic acid C2 (8). Their structures of the new triterpenes were determined as (23S)-7beta,15alpha,23-trihydroxy-3,11-dioxolanosta-8, 24(E)-diene-26-oic acid (1), (23S)-7alpha,15alpha23-trihydroxy-3,11-dioxolanosta-8, 24(E)-diene-26-oic acid (2), (23S)-3beta3,7beta, 23-trihydroxy-11,15-dioxolanosta-8,24(E)-diene-26-oic acid (3), (23S)-3beta,23-dihydroxy-7,11,15-trioxolanosta-8, 24(E)-diene-26-oic acid (4), (23S)-3beta,7beta,12beta,23-tetrahydroxy-11,15-dioxolanos ta-8,24(E)-diene-26-oic acid (5) and (23S)-3beta,12beta23-trihydroxy-7,11,15-trioxolanosta-8,24(E )-diene-26-oic acid (6), respectively, by chemical and spectroscopic means, which included the determination of a chiral center in the side chain by a modification of Mosher's method. The cytotoxicity of the compounds isolated from the Ganoderma spores was carried out in vitro against Meth-A and LLC tumor cell lines.
A systematic review may encompass both odds ratios and mean differences in continuous outcomes. A separate meta-analysis of each type of outcome results in loss of information and may be misleading. It is shown that a ln(odds ratio) can be converted to effect size by dividing by 1.81. The validity of effect size, the estimate of interest divided by the residual standard deviation, depends on comparable variation across studies. If researchers routinely report residual standard deviation, any subsequent review can combine both odds ratios and effect sizes in a single meta-analysis when this is justified.
Preclinical studies have established that the polysaccharide fractions of Ganoderma lucidum have potential antitumor activity. Recent clinical studies have demonstrated that G. lucidum polysaccharides enhance host immune functions [e.g., enhanced natural killer (NK) cell activity] in patients with advanced solid tumors, although an objective response was not observed. This open-label study aimed to evaluate the effects of water-soluble G. lucidum polysaccharides (Ganopoly, Encore International Corp., Auckland, New Zealand) on immune functions in patients with advanced lung cancer. Thirty-six patients were enrolled and treated with 5.4 g/day Ganopoly for 12 weeks. In the 30 cancer patients who completed the trial, treatment with Ganopoly did not significantly alter the mean mitogenic reactivity to phytohemagglutinin, mean counts of CD3, CD4, CD8, and CD56, mean plasma concentrations of interleukin (IL)-2, IL-6, and interferon (IFN)-gamma, or NK activity in the patients, but the results were significantly variable. However, some cancer patients demonstrated markedly modulated immune functions. The changes in IL-1 were correlated with those for IL-6, IFN-gamma, CD3, CD8, and NK activity (P < .05), and IL-2 changes were correlated with those for IL-6, CD8, and NK activity. The results suggest that subgroups of cancer patients might be responsive to Ganopoly in combination with chemotherapy/radiotherapy. Further studies are needed to explore the efficacy and safety of Ganopoly used alone or in combination with chemotherapy/radiotherapy in lung cancer patients.
Dectin-1 is a natural killer (NK)-cell-receptor-like C-type lectin that is thought to be involved in innate immune responses to fungal pathogens. This transmembrane signalling receptor mediates various cellular functions, from fungal binding, uptake and killing, to inducing the production of cytokines and chemokines. These activities could influence the resultant immune response and can, in certain circumstances, lead to autoimmunity and disease. As I discuss here, understanding the molecular mechanisms behind these functions has revealed new concepts, including collaborative signalling with the Toll-like receptors (TLRs) and the use of spleen tyrosine kinase (SYK), that have implications for the role of other non-TLR pattern-recognition receptors in immunity.
Publication bias and related bias in meta-analysis is often examined by visually checking for asymmetry in funnel plots of treatment effect against its standard error. Formal statistical tests of funnel plot asymmetry have been proposed, but when applied to binary outcome data these can give false-positive rates that are higher than the nominal level in some situations (large treatment effects, or few events per trial, or all trials of similar sizes). We develop a modified linear regression test for funnel plot asymmetry based on the efficient score and its variance, Fisher's information. The performance of this test is compared to the other proposed tests in simulation analyses based on the characteristics of published controlled trials. When there is little or no between-trial heterogeneity, this modified test has a false-positive rate close to the nominal level while maintaining similar power to the original linear regression test ('Egger' test). When the degree of between-trial heterogeneity is large, none of the tests that have been proposed has uniformly good properties.
"Lingzhi" (Ganoderma lucidum), a popular medicinal mushroom, has been used in China for longevity and health promotion since ancient times. Investigations into the anticancer activity of lingzhi have been performed in both in vitro and in vivo studies, supporting its application for cancer treatment and prevention. The proposed anticancer activity of lingzhi has prompted its usage by cancer patients. It remains debatable as to whether lingzhi is a food supplement for health maintenance or actually a therapeutic "drug" for medical proposes. Thus far there has been no report of human trials using lingzhi as a direct anticancer agent, despite some evidence showing the usage of lingzhi as a potential supplement to cancer patients. Cellular immune responses and mitogenic reactivity of cancer patients have been enhanced by lingzhi, as reported in two randomized and one nonrandomized trials, and the quality of life of 65% of lung cancer patients improved in one study. The direct cytotoxic and anti-angiogenesis mechanisms of lingzhi have been established by in vitro studies; however, clinical studies should not be neglected to define the applicable dosage in vivo. At present, lingzhi is a health food supplement to support cancer patients, yet the evidence supporting the potential of direct in vivo anticancer effects should not be underestimated. Lingzhi or its products can be classified as an anticancer agent when current and more direct scientific evidence becomes available.
Ganoderma lucidum (GL) is one of the most commonly used Chinese herbs in the oriental community, with more than 30% of pediatric cancer patients taking GL. The immunomodulating and anticancer effects exerted by GL extracts have been demonstrated by in vitro and in vivo studies. There was, however, no comparison between the immunomodulating effects of GL mycelium extract (GL-M) and spore extracts on human immune cells. Dendritic cells (DCs) are professional antigen-presenting cells and their role in DC-based tumor vaccine has been well defined. The possibility of GL as natural adjuvant for human DCs remains unknown.
This study explored the differential effect of GL-M and GL spore extract (GL-S) on proliferation and Th1/Th2 cytokine mRNA expression of human peripheral blood mononuclear cells (PBMCs) and monocytes. Their effects on the phenotypic and functional maturation of human monocyte-derived DCs were also investigated.
GL-M induced the proliferation of PBMCs and monocytes, whereas GL-S showed a mild suppressive effect. Both extracts could stimulate Th1 and Th2 cytokine mRNA expression, but GL-M was a relatively stronger Th1 stimulator. Different from GL-S, GL-M enhanced maturation of DCs in terms of upregulation of CD40, CD80, and CD86, and also reduced fluorescein isothiocyanate-dextran endocytosis. Interestingly, GLM- treated DCs only modestly enhanced lymphocyte proliferation in allogenic mixed lymphocyte culture with mild enhancement in Th development.
These findings provide evidences that GL-M has immunomodulating effects on human immune cells and therefore can be used as a natural adjuvant for cancer immunotherapy with DCs.
Many herbal medicines are widely used as immuno-modulators in Asian countries. Ganoderma lucidum (Lingzhi) is one of the most commonly used herbs in Asia and preclinical studies have established that the polysaccharide fractions of G. lucidum have potent immuno-modulating effects. However, clinical evidence for this is scanty. The present open-labeled study aimed to evaluate the effects of G. lucidum polysaccharides on selected immune functions in patients with advanced colorectal cancer. Forty-seven patients were enrolled and treated with oral G. lucidum at 5.4 g/day for 12 weeks. Selected immune parameters were monitored using various immunological methods throughout the study. In 41 assessable cancer patients, treatment with G. lucidum tended to increase mitogenic reactivity to phytohemagglutinin, counts of CD3, CD4, CD8 and CD56 lymphocytes, plasma concentrations of interleukin (IL)-2, IL-6 and interferon (IFN)-gamma, and NK activity, whereas plasma concentrations of IL-1 and tumor necrosis factor (TNF)-alpha were decreased. For all of these parameters, no statistical significance was observed when a comparison was conducted between baseline and those values after a 12-week treatment with G. lucidum. The changes of IL-1 were correlated with those for IL-6, IFN-gamma, CD3, CD4, CD8 and NK activity (p<0.05) and IL-2 changes were correlated with those for IL-6, CD8 and NK activity. The results indicate that G. lucidum may have potential immuno-modulating effect in patients with advanced colorectal cancer. Further studies are needed to explore the benefits and safety of G. lucidum in cancer patients.
Ganoderma lucidum is a wood-degrading basidiomycete with numerous pharmacological effects. Since the mushroom is very rare in nature, artificial cultivation of fruiting bodies has been known on wood logs and on sawdust in plastic bags or bottles. Biotechnological cultivation of G. lucidum mycelia in bioreactors has also been established, both on solid substrates and in liquid media by submerged cultivation of fungal biomass. The most important pharmacologically active constituents of G. lucidum are triterpenoids and polysaccharides. Triterpenoids have been reported to possess hepatoprotective, anti-hypertensive, hypocholesterolemic and anti-histaminic effects, anti-tumor and anti-engiogenic activity, effects on platelet aggregation and complement inhibition. Polysaccharides, especially beta-d-glucans, have been known to possess anti-tumor effects through immunomodulation and anti-angiogenesis. In addition, polysaccharides have a protective effect against free radicals and reduce cell damage caused by mutagens.
Investigation of ZhengQing Lingzhi liquid as adjuvant treatment on patients with colon cancer
- Leng
Study of clinical efficacy of Lingzhi spore capsule on tumour patients with chemotherapy/radiotherapy
- He
A Clinical Study on Immunity Regulation Function of Shenqi Lingzhi Regimen on Tumour Patients
- Li
Clinical investigation of Bozhi glycopeptide injection combined with chemotherapy for advanced-stage malignancy
- Song
Clinical research of Lingzhi in cancer treatment
- Wang
Clinical observation of Tian-an Lingzhi capsule in 120 patients with malignant tumours
- Xu
Clinical observation of efficacy of Ganoderm Lucidum capsule on induced toxicity of radiotherapy/chemotherapy
- Zhang
Effect of Laojunxian Lingzhi oral liquid combined with chemotherapy on non-parvicellular lung cancer at stage II and III
- Yan
Clinical comparative investigation of Bailong capsule and liquid in combination with chemotherapy for digestive tumor
- Jing
The clinical efficacy study of ginseng and Ganoderma lucidum essence - reinforcing pills combine with chemotherapy for malignant tumours
- Pan
Clinical investigation of Lingzhi spore powder in adjuvant treatment of digestive tumours
- Qi
Observation on the side effect of "Gloosy Ganoderma Spores Powder" combined with Qining injection in the treatment of 28 patients with malignant tumor and nursing care
- Wang